Black-Phosphorus-Based Orientation-Induced Diodes.
Adv Mater. 2017 Nov 23;:
Authors: Xin W, Li XK, He XL, Su BW, Jiang XQ, Huang KX, Zhou XF, Liu ZB, Tian JG
Despite many decades of research of diodes, which are fundamental components of electronic and photoelectronic devices with p-n or Schottky junctions using bulk or 2D materials, stereotyped architectures and complex technological processing (doping and multiple material operations) have limited future development. Here, a novel rectification device, an orientation-induced diode, assembled using only few-layered black phosphorus (BP) is investigated. The key to its realization is to utilize the remarkable anisotropy of BP in low dimensions and change the charge-transport conditions abruptly along the different crystal orientations. Rectification ratios of 6.8, 22, and 115 can be achieved in cruciform BP, cross-stacked BP junctions, and BP junctions stacked with vertical orientations, respectively. The underlying physical processes and mechanisms can be explained using "orientation barrier" band theory. The theoretical results are experimentally confirmed using localized scanning photocurrent imaging. These orientation-induced optoelectronic devices open possibilities for 2D anisotropic materials with a new degree of freedom to improve modulation in diodes.
PMID: 29168903 [PubMed - as supplied by publisher]
Curcumin mediated down-regulation of αV β3 integrin and up-regulation of pyruvate dehydrogenase kinase 4 (PDK4) in Erlotinib resistant SW480 colon cancer cells.
Phytother Res. 2017 Nov 23;:
Authors: Javadi S, Rostamizadeh K, Hejazi J, Parsa M, Fathi M
Erlotinib is a potent, selective, and orally active inhibitor of the epidermal growth factor receptor, but the development of erlotinib resistance during chemotherapy can lead to treatment failure. To shed light on the erlotinib-resistant pathway, this study investigated the effect of combination therapy using curcumin- and erlotinib-loaded nanoparticles on the expression of αv β3 integrin and pyruvate dehydrogenase kinase 4 (PDK4) in an erlotinib-resistant SW480 colon cancer cell line. An erlotinib-resistant SW480 colon cancer cell line was produced by long-term exposure to erlotinib. Curcumin-loaded Methoxy poly ethylene glycol Poly caprolactone (cur/mPEG-PCL) and erlotinib-loaded mPEG-PCL (erl/mPEG-PCL) micelles were provided using a single step nanoprecipitation method and used as combination therapy of resistant SW480 cancer cells. After that, gene expression levels of PDK4, αv, and β3 mRNA were determined by the semiquantitative reverse transcription-polymerase chain reaction. Protein levels of whole αv β3 integrin were evaluated using the enzyme-linked immunosorbent assay method. In SW480 cell line, the IC50 of nonresistant and resistant cells was 87.6 ± 1.2 nM and 19.1 ± 0.14 μM, for erlotinib and it was about 21.8 and 30 μM for curcumin, respectively. Although PDK4 expression was not significantly different in resistant and nonresistant cells, its expression was up regulated (1.4 fold) in resistant cells by a combination therapy of cur/mPEG-PCL at a dose of 3 μM and erl/mPEG-PCL at a dose of 5 μM. β3 mRNA and the protein level of whole αv β3 integrin was significantly higher in resistant SW480 cells as compared with those in nonresistant cells. In terms of treatment, a combination of 6-μM cur/mPEG-PCL and 5-μM erl/mPEG-PCL down regulated β3 gene expression 6.6-fold in resistant cells as compared with nonresistant cells. At the protein level, a combination of 3-μM-cur/mPEG-PCL and 10-μM erl/mPEG-PCL reduced αv β3 protein in resistant cells. The results indicated that combination therapy using cur/mPEG-PCL and erl/mPEG-PCL could decrease αv β3 integrin expression and increase PDK4 gene expression in resistant colon cancer cells, which may have effects on drug resistance signaling pathways.
PMID: 29168312 [PubMed - as supplied by publisher]
Safinamide differentially modulates in vivo glutamate and GABA release in the rat hippocampus and basal ganglia.
J Pharmacol Exp Ther. 2017 Nov 22;:
Authors: Morari M, Brugnoli A, Pisano CA, Novello S, Caccia C, Melloni E, Padoani G, Vailati S, Sardina M
Safinamide has been recently approved as add-on to levodopa therapy in Parkinson's disease. In addition to inhibiting monoamine oxidase-type B, it also blocks sodium channels and modulates glutamate release in vitro. Since this property might contribute to the therapeutic action of the drug, we undertook the present study to investigate whether safinamide inhibits glutamate release also in vivo, and whether this effect is consistent across different brain areas and is selective for glutamatergic neurons. To this aim, in vivo microdialysis was used to monitor the spontaneous and veratridine-induced glutamate and GABA release in the hippocampus and basal ganglia of naive, awake rats. Brain levels of safinamide were measured along. To shed light on the mechanisms underlying the effect of safinamide, sodium currents were measured by patch-clamp recording in rat cortical neurons. Safinamide maximally inhibited the veratridine-induced glutamate and GABA release in hippocampus at 15 mg/kg, which reached free brain concentrations of 1.89-1.37 µM. This dose attenuated the veratridine-stimulated glutamate (but not GABA) release also in subthalamic nucleus, globus pallidus and substantia nigra reticulata, but not striatum. Safinamide was ineffective on spontaneous neurotransmitter release. In vitro, safinamide inhibited sodium channels, showing greater affinity at depolarized (IC50=8 µM) than resting (IC50=262 µM) potentials. We conclude that safinamide inhibits in vivo glutamate release from stimulated nerve terminals likely via blockade of sodium channels at subpopulations of neurons with specific firing patterns. These data are consistent with the anticonvulsant and antiparkinsonian actions of safinamide, and provide support for the non-dopaminergic mechanism of its action.
PMID: 29167350 [PubMed - as supplied by publisher]
Photobiodulation Inhibits Long-Term Structural and Functional Lesions of Diabetic Retinopathy.
Diabetes. 2017 Nov 22;:
Authors: Cheng Y, Du Y, Liu H, Tang J, Veenstra A, Kern TS
Previous studies demonstrated that brief (3-4 minutes), daily application of light at 670nm to diabetic rodents inhibited molecular and pathophysiologic processes implicated in the pathogenesis of diabetic retinopathy (DR), and reversed diabetic macular edema in small numbers of patients studied. Whether or not this therapy would inhibit the neural and vascular lesions that characterize the early stages of the retinopathy was unknown. We administered photobiomodulation (PBM) therapy daily for 8 months to streptozotocin-diabetic mice, and assessed effects of PBM on visual function, retinal capillary permeability, and capillary degeneration using published methods. Vitamin D receptor and Cyp24a1 transcripts were quantified by qRT-PCR, and the abundance of c-Kit(+) stem cells in blood and retina were assessed. Long-term daily administration of PBM significantly inhibited the diabetes-induced leakage and degeneration of retinal capillaries, and significantly inhibited also the diabetes-induced reduction in visual function. PBM also inhibited diabetes-induced reductions in retinal Cyp24a1 mRNA levels and numbers of circulating stem cells (CD45(-)/c-Kit(+)), but these effects may not account for the beneficial effects of PBM on the retinopathy. PBM significantly inhibits the functional and histopathologic features of early DR, and these effects likely are mediated via multiple mechanisms.
PMID: 29167189 [PubMed - as supplied by publisher]
Photodynamic action of the red laser on Propionibacterium acnes.
An Bras Dermatol. 2017 Sep-Oct;92(5):622-625
Authors: Ramos RR, Paiva JL, Gomes JPFDS, Boer NP, Godoy JMP, Batigalia F
BACKGROUND: Photodynamic therapy is a therapeutic modality that has consolidated its activity in the photooxidation of organic matter, which arises from the activity of reactive oxygen species.
OBJECTIVE: To evaluate the effect of red laser 660nm with the photosensitizer methylene blue on Propionibacterium acnes in vitro.
METHOD: The experimental design was distributed into four groups (1 - control group without the application of light and without photosensitizer, 2 - application of light, 3 - methylene blue without light, and 4 - methylene blue with light). Tests were subjected to red laser irradiation 660nm by four cycles of 5 minutes at 3-minute intervals.
RESULTS: It was evidenced the prominence of the fourth cycle (20 minutes) groups 2, 3 and 4.
STUDY LIMITATIONS: Despite the favorable results, the laser irradiation time photosensitizer associated with methylene blue were not sufficient to to completely inhibit the proliferation of bacteria.
CONCLUSION: Further studies in vitro are recommended to enable the clinical application of this photosensitizer in photodynamic therapy.
PMID: 29166495 [PubMed - in process]
Manganese Dioxide Coated WS2 @Fe3 O4 /sSiO2 Nanocomposites for pH-Responsive MR Imaging and Oxygen-Elevated Synergetic Therapy.
Small. 2017 Nov 22;:
Authors: Yang G, Zhang R, Liang C, Zhao H, Yi X, Shen S, Yang K, Cheng L, Liu Z
Recently, the development of multifunctional theranostic nanoplatforms to realize tumor-specific imaging and enhanced cancer therapy via responding or modulating the tumor microenvironment (TME) has attracted tremendous interests in the field of nanomedicine. Herein, tungsten disulfide (WS2 ) nanoflakes with their surface adsorbed with iron oxide nanoparticles (IONPs) via self-assembly are coated with silica and then subsequently with manganese dioxide (MnO2 ), on to which polyethylene glycol (PEG) is attached. The obtained WS2 -IO/S@MO-PEG appears to be highly sensitive to pH, enabling tumor pH-responsive magnetic resonance imaging with IONPs as the pH-inert T2 contrast probe and MnO2 as the pH-sensitive T1 contrast probe. Meanwhile, synergistic combination tumor therapy is realized with such WS2 -IO/S@MO-PEG, by utilizing the strong near-infrared light and X-ray absorbance of WS2 for photothermal therapy (PTT) and enhanced cancer radiotherapy (RT), respectively, as well as the ability of MnO2 to decompose tumor endogenous H2 O2 and relieve tumor hypoxia to further overcome hypoxia-associated radiotherapy resistance. The combination of PTT and RT with WS2 -IO/S@MO-PEG results in a remarkable synergistic effect to destruct tumors. This work highlights the promise of developing multifunction nanocomposites for TME-specific imaging and TME modulation, aiming at precision cancer synergistic treatment.
PMID: 29165872 [PubMed - as supplied by publisher]
Mechanisms and Mitochondrial Redox Signaling in Photobiomodulation.
Photochem Photobiol. 2017 Nov 22;:
Authors: Hamblin MR
Photobiomodulation (PBM) involves the use of red or near-infrared light at low power densities to produce a beneficial effect on cells or tissues. PBM therapy is used to reduce pain, inflammation, edema, and to regenerate damaged tissues such as wounds, bones and tendons. The primary site of light absorption in mammalian cells has been identified as the mitochondria, and more specifically, cytochrome c oxidase (CCO). It is hypothesized that inhibitory nitric oxide can be dissociated from CCO thus restoring electron transport and increasing mitochondrial membrane potential. Another mechanism involves activation of light or heat-gated ion channels. This review will cover the redox signaling that occurs in PBM and examine the difference between healthy and stressed cells, where PBM can have apparently opposite effects. PBM has a marked effect on stem cells, and this is proposed to operate via mitochondrial redox signaling. PBM can act as a pre-conditioning regimen, and can interact with exercise on muscles. This article is protected by copyright. All rights reserved.
PMID: 29164625 [PubMed - as supplied by publisher]
Neurological Complications of HIV Infection.
Curr Infect Dis Rep. 2017 Nov 21;19(12):50
Authors: Farhadian S, Patel P, Spudich S
PURPOSE OF REVIEW: HIV-associated neurocognitive disorders (HAND) are common in patients with HIV disease, even during suppressive combination antiretroviral therapy (cART). This review article addresses the pathogenesis of HAND, focusing on important findings from the last 5 years.
RECENT FINDINGS: While HIV-associated dementia is now rare in settings with cART availability, mild forms of HAND are increasing in prevalence. Biomarkers of cellular injury, such as neurofilament light chain and neopterin, can detect early stages of neuroinflammation associated with HIV infection and are increased even in asymptomatic individuals with chronic HIV infection. Several recent studies form a growing body of evidence that HIV can infect and replicate in monocytes and that blocking monocyte activity can potentially improve neurological outcomes in HIV. Early cART may also prevent HAND. Understanding the multifactorial causes of CNS infection and inflammation is critical to devising treatment and preventive strategies for HAND.
PMID: 29164407 [PubMed]
Effect of a cognitive task and light finger touch on standing balance in healthy adults.
Exp Brain Res. 2017 Nov 21;:
Authors: Lee Y, Goyal N, Aruin AS
The purpose of the study was to investigate the individual and combined effects of applying light finger touch and performing a cognitive task on postural sway. Fourteen healthy young individuals stood on the force platform with light finger touch contact applied to an external stable structure and without finger touch. Both tasks were performed with and without a cognitive task (counting backward from a randomly chosen three-digit number). The center of pressure excursion and velocity as well as sway area were calculated. Participants demonstrated significantly smaller postural sway in the presence of a finger touch contact (p < 0.05), while postural sway was increased during the performance of the cognitive task (p < 0.05). When two tasks were performed simultaneously, body sway increased as compared to standing with light touch only (p < 0.05) and decreased when compared to standing and performing the cognitive task only (p < 0.05). This suggests that a positive effect of finger touch on body sway could be diminished by the simultaneous performance of a cognitive task. The outcome provides a foundation for future studies of the individual and combined effects of light finger touch and cognitive tasks on postural control.
PMID: 29164286 [PubMed - as supplied by publisher]
Fluorous photosensitizers enhance photodynamic therapy with perfluorocarbon nanoemulsions.
Chem Commun (Camb). 2017 Nov 22;:
Authors: Day RA, Estabrook DA, Logan JK, Sletten EM
Photodynamic therapy (PDT) requires a photosensitizer, light, and oxygen to induce cell death. The majority of efforts to advance PDT focus only on the first two components. Here, we employ perfluorocarbon nanoemulsions to simultaneously deliver oxygen and a photosensitizer. We find that the implementation of fluorous soluble photosensitizers enhances the efficacy of PDT.
PMID: 29164187 [PubMed - as supplied by publisher]
Childhood lupus nephritis: 12 years of experience from a developing country's perspective.
Eur J Rheumatol. 2017 Sep;4(3):178-183
Authors: Samanta M, Nandi M, Mondal R, Hazra A, Sarkar S, Sabui T, Kundu CK, Biswas A
Objective: To assess the long-term outcome of lupus nephritis in children with systemic lupus erythematosus followed up over 12 years at a tertiary care teaching hospital in Eastern India.
Material and Methods: This is a retrospective observational study of the clinicopathological presentation, management, and outcome in 46 children with lupus nephritis over a period of 12 years at a tertiary teaching hospital in Eastern India. Mortality was compared between different lupus classes and therapy groups with Kaplan-Meier analysis and log-rank test.
Results: The incidence of lupus nephritis was 58.97% [95% confidence interval (CI) 48.06%-59.89%] with the mean age at presentation being 10.2±2.43 years (range 5.5-14.5) years. Majority belonged to class IV (30.43%), followed by class II (26.91%), class III (23.91), and class V (8.70%). Outcome analysis of children with lupus nephritis over 12 years revealed that 24 (52.17%) achieved complete remission of disease activity, 5 attained partial remission, 4 continued to have active disease, 5 developed end-stage renal disease (ESRD), and 8 died. Overall mortality thus observed was 17.39% with septicemia in the background of ESRD being the commonest cause. No significant difference in mortality was observed between different lupus nephritis classes or therapy arm groups.
Conclusion: The study throws light on various aspects of lupus nephritis and their long-term outcome patterns in children from developing countries such as India.
PMID: 29163999 [PubMed]
Use of a social media network to reduce early neonatal mortality: a preliminary report from a quality improvement project in Yaoundé, Cameroon.
Matern Health Neonatol Perinatol. 2017;3:26
Authors: Amani A, Nansseu JR, Mah EM, Vougmo CM, Moluh SM, Mbu R
Background: Perinatal networks have yielded substantial contribution in decreasing the neonatal mortality rate. We present here the process of implementation of a perinatal network in Yaoundé (Cameroon) based on the WhatsApp messenger application as well as some preliminary results and achievements.
Methods: In December 2016, the Yaoundé Perinatal Network was launched, regrouping a multidisciplinary team of health professionals dealing with perinatal care in Yaoundé, Cameroon. The network takes advantage of WhatsApp facilities and is coordinated by 5 administrators. One of their main duties is to have a twice-daily updated status of the available equipment (incubators, oxygen and phototherapy) and bed capacities across the Yaoundé pediatric units. Once a request is sent through the network, other members react, either by giving advice or by telling where the desired equipment or expertise is available at that moment. Then, the baby is immediately prepared for transfer, occurring once the receiving pediatric unit has attested that it is already prepared to receive the new patient.
Results: From December 18, 2016 to July 31, 2017, 139 members representing all the principal maternities and tertiary pediatric units in Yaoundé were already included in the network. The network permitted instant sharing of knowledge and information between its members for an optimal delivery of care. Two hundred and seventeen neonates were transferred using the network; the median time of response after a request had been sent was 19.5 min and the delay in transferring a neonate averaged 70 min.
Conclusion: Taking account of the preliminary promising notes, there is hope that the Yaoundé Perinatal Network will help to reduce neonatal mortality in our context. Lessons learned from its implementation will serve to replicate this innovative health action in other towns of the country. Moreover, this experience could be a source of inspiration for other countries facing similar challenges.
PMID: 29163979 [PubMed]
Structural basis of the therapeutic anti-PD-L1 antibody atezolizumab.
Oncotarget. 2017 Oct 27;8(52):90215-90224
Authors: Zhang F, Qi X, Wang X, Wei D, Wu J, Feng L, Cai H, Wang Y, Zeng N, Xu T, Zhou A, Zheng Y
Monoclonal antibodies targeting PD-1/PD-L1 signaling pathway have achieved unprecedented success in cancer treatment over the last few years. Atezolizumab is the first PD-L1 monoclonal antibody approved by US FDA for cancer therapy; however the molecular basis of atezolizumab in blocking PD-1/PD-L1 interaction is not fully understood. Here we have solved the crystal structure of PD-L1/atezolizumab complex at 2.9 angstrom resolution. The structure shows that atezolizumab binds the front beta-sheet of PD-L1 through three CDR loops from the heavy chain and one CDR loop from the light chain. The binding involves extensive hydrogen-bonding and hydrophobic interactions. Notably there are multiple aromatic residues from the CDR loops forming Pi-Pi stacking or cation-Pi interactions within the center of the binding interface and the buried surface area is more than 2000 Å(2), which is the largest amongst all the known PD-L1/antibody structures. Mutagenesis study revealed that two hot-spot residues (E58, R113) of PD-L1 contribute significantly to the binding of atezolizumab. The structure also shows that atezolizumab binds PD-L1 with a distinct heavy and light chain orientation and it blocks PD-1/PD-L1 interaction through competing with PD-1 for the same PD-L1 surface area. Taken together, the complex structure of PD-L1/atezolizumab solved here revealed the molecular mechanism of atezolizumab in immunotherapy and provides basis for future monoclonal antibody optimization and rational design of small chemical compounds targeting PD-L1 surface.
PMID: 29163822 [PubMed]
Pulse frequency dependency of photobiomodulation on the bioenergetic functions of human dental pulp stem cells.
Sci Rep. 2017 Nov 21;7(1):15927
Authors: Kim HB, Baik KY, Choung PH, Chung JH
Photobiomodulation (PBM) therapy contributes to pain relief, wound healing, and tissue regeneration. The pulsed wave (PW) mode has been reported to be more effective than the continuous wave (CW) mode when applying PBM to many biological systems. However, the reason for the higher effectiveness of PW-PBM is poorly understood. Herein, we suggest using delayed luminescence (DL) as a reporter of mitochondrial activity after PBM treatment. DL originates mainly from mitochondrial electron transport chain systems, which produce reactive oxygen species (ROS) and adenosine triphosphate (ATP). The decay time of DL depends on the pulse frequencies of applied light, which correlate with the biological responses of human dental pulp stem cells (hDPSCs). Using a low-power light whose wavelength is 810 nm and energy density is 38 mJ/cm(2), we find that a 300-Hz pulse frequency prolonged the DL pattern and enhanced alkaline phosphatase activity. In addition, we analyze mitochondrial morphological changes and their volume density and find evidence supporting mitochondrial physiological changes from PBM treatment. Our data suggest a new methodology for determining the effectiveness of PBM and the specific pulse frequency dependency of PBM in the differentiation of hDPSCs.
PMID: 29162863 [PubMed - in process]
Liposomes assembled from dimeric retinoic acid phospholipid with improved pharmacokinetic properties.
Eur J Pharm Sci. 2017 Nov 18;:
Authors: Lu L, Du Y, Ismail M, Ling L, Yao C, Fu Z, Li X
All-trans-retinoic acid (ATRA) exhibits potent cytotoxicities against different cancer cells by binding to retinoic acid receptors (RARs), which is regarded as the first example of targeted therapy in acute promyelocytic leukemia (APL). However, its extensive clinical applications have been limited because of poor aqueous solubility, short half-life time and side effects. In this report, dimeric ATRA phosphorylcholine prodrug (Di-ATRA-PC) was designed and assembled into nanoliposomes to improve its pharmacokinetic properties. Di-ATRA-PC prodrug was synthesized by a facile esterification and characterized by mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (NMR). The Di-ATRA-PC assembled liposomes were prepared by thin film hydration method with ATRA loading efficiency up to 73wt%. The liposomes have a uniform particle size (73.1±3.6nm) with negatively charged surface (-20.5±2.5mV) and typical lipid bilayer structure as measured by dynamic light scattering (DLS), transmission electron microscope (TEM) and cryogenic transmission electron microscope (cryo-TEM). In vitro drug release study confirmed that Di-ATRA-PC liposomes could sustainedly release free ATRA in a weakly acidic condition. Furthermore, cellular uptake, MTT and cell apoptosis analysis demonstrated that the liposomes could be successfully internalized into tumor cells to induce apoptosis of MCF-7 and HL-60 cells. More importantly, in vivo pharmacokinetic assay indicated that Di-ATRA-PC liposomes had much longer retention time in comparison with ATRA. In conclusion, Di-ATRA-PC liposomal formulation could be a potential drug delivery system of ATRA with enhanced pharmacokinetic properties.
PMID: 29162478 [PubMed - as supplied by publisher]
[Prematurity and nursing care in neonatal intensive care].
Soins Pediatr Pueric. 2017 Nov - Dec;38(299):29-31
Authors: Laforêt N, Moughalme M, Dumas-Laussinotte A, Lecomte C
In neonatal intensive care, the management of babies born prematurely requires particular vigilance from caregivers. Specific care procedures include enteral feeding and the development of the diet, the monitoring of vital signs, venous access management, blood withdrawal, phototherapy and obligatory screening. The nursing role is essential in this context.
PMID: 29162256 [PubMed - in process]
Potentiating angiogenesis arrest in vivo via laser irradiation of peptide functionalised gold nanoparticles.
J Nanobiotechnology. 2017 Nov 21;15(1):85
Authors: Pedrosa P, Heuer-Jungemann A, Kanaras AG, Fernandes AR, Baptista PV
BACKGROUND: Anti-angiogenic therapy has great potential for cancer therapy with several FDA approved formulations but there are considerable side effects upon the normal blood vessels that decrease the potential application of such therapeutics. Chicken chorioallantoic membrane (CAM) has been used as a model to study angiogenesis in vivo. Using a CAM model, it had been previously shown that spherical gold nanoparticles functionalised with an anti-angiogenic peptide can humper neo-angiogenesis.
RESULTS: Our results show that gold nanoparticles conjugated with an anti-angiogenic peptide can be combined with visible laser irradiation to enhance angiogenesis arrest in vivo. We show that a green laser coupled to gold nanoparticles can achieve high localized temperatures able to precisely cauterize blood vessels. This combined therapy acts via VEGFR pathway inhibition, leading to a fourfold reduction in FLT-1 expression.
CONCLUSIONS: The proposed phototherapy extends the use of visible lasers in clinics, combining it with chemotherapy to potentiate cancer treatment. This approach allows the reduction of dose of anti-angiogenic peptide, thus reducing possible side effects, while destroying blood vessels supply critical for tumour progression.
PMID: 29162137 [PubMed - in process]
Modern Fixed Imaging Systems Reduce Radiation Exposure to Patients and Providers.
Vasc Endovascular Surg. 2017 Jan 01;:1538574417742211
Authors: Stangenberg L, Shuja F, van der Bom IMJ, van Alfen MHG, Hamdan AD, Wyers MC, Guzman RJ, Schermerhorn ML
High-definition fluoroscopic imaging is required to perform endovascular procedures safely and precisely, especially in complex cases, resulting in longer procedures and increased radiation exposure. This is of importance for training institutions as trainees, even with sound instruction in as low as reasonably achievable (ALARA) principles, tend to have high radiation exposures. Recently, there was an upgrade in the imaging system allowing for comparison of radiation exposure to patients and providers. We performed an analysis of consecutive endovascular aneurysm repair (EVAR) and superficial femoral artery (SFA) interventions in the years 2013 to 2014. We recorded body mass index (BMI) and fluoroscopy time (FT) and subsequently matched 1:1 based on BMI, FT, or both. We determined radiation dose using air kerma (AK) and also recorded individual surgeons' badge readings. Allura Xper FD20 was upgraded to AlluraClarity with ClarityIQ. We identified a total of 77 EVARs (52 pre and 25 post) and 134 SFA interventions (99 pre and 35 post). Unmatched results for EVAR were BMI pre 26.2 versus post 25.8 (kg/m(2), P = .325), FT 28.1 versus 21.2 (minutes, P = .051), and AK 1178.5 versus 581 (mGy, P < .001), respectively. After matching, there was a 53.2% reduction in AK (846.1 vs 395.9 mGy; P = .004) for EVAR. Unmatched results for SFA interventions were BMI pre 28.1 versus post 26.6 ( P = .327), FT 18.7 versus 16.2 ( P = .282), and AK 285.6 versus 106.0 ( P < .001), respectively. After matching, there was a 57.0% reduction in AK (305.0 vs 131.3, P < .001). The total deep dose equivalent from surgeons' badge readings decreased from 39.5 to 17 mrem ( P = .029). Aortic and peripheral endovascular interventions can be performed with reduced radiation exposure to patients and providers, employing modern fixed imaging systems with advanced dose reduction technology. This is of particular importance in the light of the increasing volume and complexity of endovascular and hybrid procedures as well as the prospect of decades of radiation exposure during training and practice.
PMID: 29162024 [PubMed - as supplied by publisher]
Micronuclei assay in exfoliated buccal cells of radiation treated oral cancer patients.
J Exp Ther Oncol. 2017 Nov;12(2):121-128
Authors: Ramesh G, Chaubey S, Raj A, Seth RK, Katiyar A, Kumar A
BACKGROUND: Micronuclei are suitable internal dosimeters for revealing tissue-specific genotoxic damage in individuals exposed to carcinogenic mixtures. Evaluation of radiation-induced cellular changes to predict radiosensitivity has invested many investigators since such changes were first found in biopsy material.
AIM: The aim of the present study was to assess the relationship of with histopathological grade and number of radiation therapy sittings with the frequency of micronuclei and nuclear anomalies among oral cancer patients.
MATERIAL & METHOD: Thirty male patients with histologically proven cases of oral cancer undergoing radiation therapy and age and sex matched 20 healthy controls were included in the study. Scrape cytology smears of exfoliated buccal cells were prepared and stained using Feulgen stain and frequency of micronuclei and other nuclear anomalies counts were evaluated with the help of light microscope expressed as per 1000 buccal cells.
RESULTS: The mean values of the micronuclei and nuclear anomalies were 14.03 and 21.30 respectively. There was a significant association and strong positive correlation of Radiation exposure and grades of squamous cell carcinoma with micronuclei and nuclear anomalies. There was no statistically significant association and correlation between nuclear anomalies in well differentiated and moderately differentiated carcinomas.
CONCLUSION: With increase number of radiation therapy sittings, there was increase in number of micronuclei and nuclear anomalies. Hence the result of this study highlights that increased number of micronuclei and nuclear anomalies provides information regarding radiosensitivity of epithelial cells.
PMID: 29161779 [PubMed - in process]
Highly efficient destruction of squamous carcinoma cells of the head and neck by photochemical internalization of Ranpirnase.
J Exp Ther Oncol. 2017 Nov;12(2):113-120
Authors: Liebers N, Holland-Letz T, Welschof M, Høgset A, Jäger D, Arndt MAE, Krauss J
Introduction: Photochemical Internalization is a novel drug delivery technology for cancer treatment based on the principle of Photodynamic Treatment. Using a photosensitizer that locates in endocytic vesicles membranes of tumor cells, Photochemical internalization enables cytosolic release of endocytosed antitumor agents in a site-specific manner. The purpose of the present in-vitro study was to explore whether Photochemical Internalization is able to enhance the efficacy of Ranpirnase, a cytotoxic amphibian ribonuclease, for eradication of squamous cell carcinoma of the head and neck.
Methods: Cell viability was measured in 8 primary human cell lines of squamous cell carcinoma of the head and neck after treatment with Ranpirnase and Photochemical Internalization. For Photochemical Internalization the photosensitizer disulfonated tetraphenyl porphine was incubated with tumor cells followed by exposure to blue light (435 nm).
Results: Our study demonstrates significant enhancement of antitumor activity of Ranpirnase by Photochemical Internalization. Treatment responses were heterogeneous between the primary cancer cell lines. Combining Photochemical Internalization with Ranpirnase resulted in 4.6 to 1,940-fold increased cytotoxicity when compared with the ribonuclease alone (P < 0.05).
Conclusion: Cytotoxicity of Ranpirnase can be markedly enhanced by Photochemical Internalization in squamous cell carcinoma of the head and neck.
PMID: 29161778 [PubMed - in process]
Phosphatidylserine targeted single-walled carbon nanotubes for photothermal ablation of bladder cancer.
Nanotechnology. 2017 Nov 21;:
Authors: Virani NA, Davis C, McKernan P, Hauser P, Hurst RE, Slaton J, Silvy RP, Resasco DE, Harrison RG
Bladder cancer has a 60-70% recurrence rate most likely due to residual tumour left behind after a transurethral resection (TUR). Failure to completely resect the cancer can lead to recurrence and progression into higher grade tumours with metastatic potential. We present here a novel therapy to treat superficial tumours with the potential to decrease recurrence. The therapy is a heat-based approach in which bladder tumour specific single-walled carbon nanotubes (SWCNTs) are delivered intravesically at a very low dose (0.1 mg SWCNT per kg body weight) followed 24 hours later by a short 30 second treatment with a 360°near-infrared light that heats only the bound nanotubes. The energy density of the treatment was 50 J cm-2, and the power density that this treatment corresponds to is 1.7 W cm-2, which is relatively low. Nanotubes are specifically targeted to the tumour via the interaction of annexin V (AV) and phosphatidylserine, which is normally internalized on healthy tissue but externalized on tumours and the tumour vasculature. SWCNTs are conjugated to AV, which binds specifically to bladder cancer cells as confirmed in vitro and in vivo. Due to this specific localization, NIR light can be used to heat the tumour while conserving the healthy bladder wall. In a short-term efficacy study in mice with orthotopic MB49 murine bladder tumours treated with the SWCNT-AV conjugate and NIR light, no tumours were visible on the bladder wall 24 hours after NIR light treatment, and there was no damage to the bladder. In a separate survival study in mice with the same type of orthotopic tumours, there was a 50% cure rate at 116 days when the study was ended. At 116 days, no treatment toxicity was observed, and no nanotubes were detected in the clearance organs or bladder.
PMID: 29160225 [PubMed - as supplied by publisher]
Near-infrared light-responsive nanoparticles for improved anticancer efficacy through synergistic chemo-photothermal therapy.
Pharm Dev Technol. 2017 Nov 21;:1-9
Authors: Li Y, Xiao BX, Dong J, Liu Y, Gao S, Pang J, Sun Z
Combined treatment is more effective than single treatment against most forms of cancer. The synergistic chemo-thermotherapy mediated by nanoparticles has superior advantages of lesser adverse effects as a promising cancer therapy modality. In this study, we report a theranostic carrier system co-encapsulating Doxorubicin (DOX) and Indocyanine green (ICG) into the D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS). Full physicochemical characterization studies of the DOX/ICG-loaded TPGS nanoparticles (TNPs) are performed. TNPs have a mean size around 60 nm with superior photostability, and entrapment efficiency of drugs in TNPs was 75.0% for ICG and 68.3% for DOX. TNPs also exhibit a longer sustained release with around 63% of the entrapped drug in 24 h. In vitro studies, TNPs could effectively enhance cellular uptake of DOX and ICG, which permitted high therapeutic efficacy against cancer cells. Further, we investigate antitumor efficacy of TNPs along with its impact on major organs in vivo, TNPs also exhibit a complete inhibition of tumor growth and minimal side effects after irradiation. Collectively, these results suggest that near-infrared light-responsive TNPs can further enhance antitumor effects by synergistic chemo-photothermal therapy.
PMID: 29160121 [PubMed - as supplied by publisher]
Quality assurance for a six degrees-of-freedom table using a 3D printed phantom.
J Appl Clin Med Phys. 2017 Nov 21;:
Authors: Woods K, Ayan AS, Woollard J, Gupta N
PURPOSE: To establish a streamlined end-to-end test of a 6 degrees-of-freedom (6DoF) robotic table using a 3D printed phantom for periodic quality assurance.
METHODS: A 3D printed phantom was fabricated with translational and rotational offsets and an imbedded central ball-bearing (BB). The phantom underwent each step of the radiation therapy process: CT simulation in a straight orientation, plan generation using the treatment planning software, setup to offset marks at the linac, registration and corrected 6DoF table adjustments via hidden target test, delivery of a Winston-Lutz test to the BB, and verification of table positioning via field and laser lights. The registration values, maximum total displacement of the combined Winston-Lutz fields, and a pass or fail criterion of the laser and field lights were recorded. The quality assurance process for each of the three linacs were performed for the first 30 days.
RESULTS: Within a 95% confidence interval, the overall uncertainty values for both translation and rotation were below 1.0 mm and 0.5° for each linac respectively. When combining the registration values and other uncertainties for all three linacs, the average deviations were within 2.0 mm and 1.0° of the designed translation and rotation offsets of the 3D print respectively. For all three linacs, the maximum total deviation for the Winston-Lutz test did not exceed 1.0 mm. Laser and light field verification was within tolerance every day for all three linacs given the latest guidance documentation for table repositioning.
CONCLUSION: The 3D printer is capable of accurately fabricating a quality assurance phantom for 6DoF positioning verification. The end-to-end workflow allows for a more efficient test of the 6DoF mechanics while including other important tests needed for routine quality assurance.
PMID: 29159920 [PubMed - as supplied by publisher]
Juvenile mycosis fungoides with large-cell transformation: Successful treatment with psoralen with ultraviolet A light, interferon-alfa, and localized radiation.
Pediatr Dermatol. 2017 Nov 21;:
Authors: Chan WH, Lewis DJ, Hinojosa T, Curry JL, Duvic M
Mycosis fungoides with large-cell transformation is historically associated with a poor prognosis. Pediatric cases of mycosis fungoides with large-cell transformation are rare, with only three other cases reported in the literature. We present the first case of a child with almost complete remission of his mycosis fungoides with large-cell transformation shortly after administration of psoralen plus ultraviolet A, interferon-alfa, and localized radiation.
PMID: 29159918 [PubMed - as supplied by publisher]
Non-pharmacological interventions in patients with spinal cord compression: a systematic review.
J Neurooncol. 2017 Nov 20;:
Authors: Paniagua-Collado M, Cauli O
Spinal cord compression is a complex and challenging condition that greatly affects the quality of life. Non-pharmacological techniques have only been studied to a very lesser extent; although they are evidence to be beneficial. We performed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) analysis of the scientific literature in several databases (Medline, Cochrane, Scopus, Cuiden, Pubmed, Lilacs and Embase); using the following keywords: spinal cord compression, spine compression, mobilization, positioning, brace and bracing. Eleven studies met the inclusion criteria and were finally included in the systematic review. 3 of them were related to metastatic spinal cord compression, 5 to spinal cord compression due to other causes and the last 3 of them regarded the health professional´s knowledge in oncology patients. In all cases, it seems possible to manage spinal cord compression by using external mobilization and braces and that this treatment is beneficial to patients. Positioning plays a massive role in the disease and can improve or worsen the condition when used improperly; the supine position is overused and can have a negative impact both physically and psychologically. Non-pharmacological interventions could be useful for pain management, cardiovascular alterations and patients' well-being. One randomized clinical trial demonstrated that massage therapy, using either broad compression massage or light contact touch massage improved pain control. There is an urgent need of randomized clinical trials with these interventions in order to achieve an improved care of these patients.
PMID: 29159776 [PubMed - as supplied by publisher]
Thermoresponsive graphene oxide - starch micro/nanohydrogel composite as biocompatible drug delivery system.
Authors: Sattari M, Fathi M, Daei M, Erfan-Niya H, Barar J, Entezami AA
Introduction: Stimuli-responsive hydrogels, which indicate a significant response to the environmental change (e.g., pH, temperature, light, …), have potential applications for tissue engineering, drug delivery systems, cell therapy, artificial muscles, biosensors, etc. Among the temperature-responsive materials, poly (N-isopropylacrylamide) (PNIPAAm) based hydrogels have been widely developed and their properties can be easily tailored by manipulating the properties of the hydrogel and the composite material. Graphene oxide (GO), as a multifunctional and biocompatible nanosheet, can efficiently improve the mechanical strength and response rate of PNIPAAm-based hydrogels. Here, hydrogel composites (HCs) of PNIPAAm with GO was developed using the modified starch as a biodegradable cross-linker. Methods: Micro/nanohydrogel composites were synthesized by free radical polymerization of NIPAAm in the suspension of different feed ratio of GO using maleate-modified starch (St-MA) as cross-linker and Tetrakis (hydroxymethyl) phosphonium chloride (THPC) as a strong oxygen scavenger. The HCs were characterized by FT-IR, DSC, TGA, SEM, and DLS. Also, the phase transition, swelling/deswelling behavior, hemocompatibility and biocompatibility of the synthesized HCs were investigated. Results: The thermal stability, phase transition temperature and internal network crosslinking of HCs increases with increasing of the GO feed ratio. Also, the swelling/deswelling, hemolysis, and MTT assays studies confirmed that the HCs are a fast response, hemocompatible and biocompatible materials. Conclusion: The employed facile approach for the synthesis of HCs yields an intelligent material with great potential for biomedical applications.
PMID: 29159144 [PubMed]
Curative Metatarsal Bone Surgery Combined with Intralesional Administration of Recombinant Human Epidermal Growth Factor in Diabetic Neuropathic Ulceration of the Forefoot: A Prospective, Open, Uncontrolled, Nonrandomized, Observational Study.
Curr Ther Res Clin Exp. 2017;85:2-7
Authors: Garcia Herrera AL, Febles Sanabria RJ, Acosta Cabadilla LLÁ, Moliner Cartaya M
Background: Curative surgery is performed for a foot with ulcers and loss of protective sensation to heal the wound and prevent amputation. Evidence supports that patients with diabetes have decreased concentrations of growth factors in their tissues, notably epidermal growth factor (EGF). Injecting EGF deep into the bottom of the wound and its contours encourages a more effective response in terms of granulation tissue growth and wound closure.
Objective: To assess the effectiveness and safety of curative metatarsal bone surgery combined with intralesional administration of human recombitant EGF in neuropathic diabetic forefoot ulceration.
Methods: A prospective, open-label study of the effectiveness and safety of curative metatarsal bone surgery combined with intralesional administration of human recombitant EGF in neuropathic ulceration of the forefoot in patients with diabetes was conducted on a convenience sample of 212 patients with diabetes who had a total of 231 neuropathic ulcerations of the forefoot. The eligibility criteria included normal physical activity without a history of minor amputation and meeting the inclusion criteria without meeting any of the exclusion criteria in the Vascular Surgery Service of the Clinic Surgical Hospital "José R. López Tabrane" from January 2009 to May 2015. The follow-up process ended in November 2015, which was based on nonprobability consecutive sampling of 128 patients with diabetes who had a total of 131 foot ulcers in the treatment group and 84 patients with diabetes who had a total of 100 foot ulcers in the control group.
Results: The groups had comparable demographic and baseline characteristics. In the recombitant human EGF study group, there was a 2.1-fold shorter time of re-epithelization (healing), less recidivism, and a 2.3-fold decrease in lesions, which favored the selected treatment. The safety profile was appropriate according to the low frequency of complications and the light or moderate characteristics of the complications. Only shivering and fever were more frequent in the recombitant human EGF-treated group.
Conclusions: The combination of curative metatarsal bone surgery with intralesional administration of recombinant human EGF resulted in a significant reduction in the re-epithelization time, recidivism, and development of new diabetic lesions. The safety profile was appropriate. However, more randomized, triple-blind, and placebo trials are needed to evaluate the efficacy and safety of this new therapy.
PMID: 29158852 [PubMed - in process]
Temperature-Sensitive Gold Nanoparticle-Coated Pluronic-PLL Nanoparticles for Drug Delivery and Chemo-Photothermal Therapy.
Authors: Sun Y, Wang Q, Chen J, Liu L, Ding L, Shen M, Li J, Han B, Duan Y
Gold nanoparticle-coated Pluronic-b-poly(L-lysine) nanoparticles (Pluronic-PLL@Au NPs) were synthesized via an easy one-step method and employed as carriers for the delivery of paclitaxel (PTX) in chemo-photothermal therapy, in which Pluronic-PLL acts as the reductant for the formation of AuNPs without the need for an additional reducing agent.
METHODS: The deposition of AuNPs on the surface of Pluronic-PLL micelles and the thermal response of the system were followed via ultraviolet-visible spectroscopy and dynamic light scattering. Calcein-AM and MTT assays were used to study the cell viability of MDA-MB-231 cells treated with PTX-loaded Pluronic-PLL@Au NPs, and we then irradiated the cells with NIR light.
RESULTS: An obvious temperature response was observed for the Pluronic-PLL@Au NPs. Blood compatibility and in vitro cytotoxicity assays confirmed that the Pluronic-PLL@Au NPs have excellent biocompatibility. Compared to Taxol, the PTX-loaded Pluronic-PLL@Au NPs exhibited higher cytotoxicity in MDA-MB-231 cells. All of these results and confocal laser scanning microscopy analysis results suggest that Pluronic-PLL@Au NPs greatly enhance the cellular uptake efficiency of the drug.
CONCLUSION: As confirmed by in vitro and in vivo studies, the combination of chemotherapy and photothermal therapy can cause more damage than chemo- or photothermal therapy did alone, demonstrating the synergistic effect of chemo-photothermal treatment. Thus, the as-prepared Pluronic-PLL@Au NPs are promising for chemo-photothermal therapy.
PMID: 29158837 [PubMed - in process]
Assessment of chronic pain and access to pain therapy: a cross-sectional population-based study.
J Pain Res. 2017;10:2577-2584
Authors: Del Giorno R, Frumento P, Varrassi G, Paladini A, Coaccioli S
Background: Chronic pain (CP) has been shown as an important public health problem, and several studies emphasize the need to strengthen the health care and social systems to reduce its marginalization. This study aimed to: evaluate the epidemiology of CP in the general population in an Italian area; and assess the awareness of a specific law, unanimously approved in Parliament, which provides citizens the right to access pain management (Italian Law 38/2010).
Methods: A cross-sectional population-based study carried out during the spring of 2014 at Narni, Umbria, Italy. All the citizens residing in that area, aged >18, were enrolled in the study. Outcome measures were: prevalence of CP and therapies. The awareness of the Italian Law 38/2010 was also recorded.
Results: Data of 1293 questionnaires were analyzed. The prevalence of CP was 28.4%. In 51.5% of cases, pain was severe, with higher prevalence in females (p<0.001). Moreover, pain was generally increasing with age (p<0.001). The risk of suffering from severe pain was modeled using logistic regression. Significant predictors were female gender (OR 2.59; 95% CI: 1.77-3.79), living in an urban area (OR 0.63; 95% CI 0.45-0.88), and age (OR 1.06; 95% CI: 1.04-1.08). Among people with CP, 77.9% were receiving therapy; the proportion of individuals in therapy for severe pain significantly increased with age (OR 1.03; 95% CI: 1.02-1.05) and was smaller in individuals with light pain (OR 0.21; 95% CI: 0.07-0.66). The majority of subjects (61.9%) are not aware of the existence of a specific law stating their rights to receive pain management.
Conclusion: CP, at least in the rural part of the community investigated in Italy, is not perceived as a chronic disease in its own right. A socio-cultural transformation in patients and in the health care system seems necessary.
PMID: 29158689 [PubMed]
Current and novel approaches for control of dental biofilm.
Int J Pharm. 2017 Nov 17;:
Authors: Fernandes T, Bhavsar C, Sawarkar S, D'souza A
Insights in oral demographics have revealed that a significant percentage of population faces chronic incidences of oral diseases. The innervation of these oral manifestations is required because untreated conditions may lead to bone loss in the oral cavity and systemic complications. Conventional treatments include surgery of the affected area followed by its management and/or treatment with antibiotics. However, widely used antibiotics like Triclosan have serious side effects including down-regulation of oral keratinocytes and fibroblasts. Thus, novel treatments with more targeted approaches have been under investigation. Treatment modalities like Viral mediated gene delivery, liposomes, nanoparticles, and nanobubbles not only help in management of oral diseases but also aid in reducing the biofilm formed due to bacterial bioburden in the areas less accessible through oral and conventional means. This review focuses on the limitation of conventional treatments and highlights the recent investigations in the use of the novel treatment approaches in order to increase the patient compliance and alleviation of side effects. The authors have also tried to emphasize on the future perspectives of glucansucrase inhibitors, photodynamic therapy and probiotics as targeted drug delivery systems. However, further investigations are necessary for implementation of these novel approaches in the clinical setup.
PMID: 29157962 [PubMed - as supplied by publisher]
Glioblastoma and glioblastoma stem cells are dependent on functional MTH1.
Oncotarget. 2017 Oct 17;8(49):84671-84684
Authors: Pudelko L, Rouhi P, Sanjiv K, Gad H, Kalderén C, Höglund A, Squatrito M, Schuhmacher AJ, Edwards S, Hägerstrand D, Berglund UW, Helleday T, Bräutigam L
Glioblastoma multiforme (GBM) is an aggressive form of brain cancer with poor prognosis. Cancer cells are characterized by a specific redox environment that adjusts metabolism to its specific needs and allows the tumor to grow and metastasize. As a consequence, cancer cells and especially GBM cells suffer from elevated oxidative pressure which requires antioxidant-defense and other sanitation enzymes to be upregulated. MTH1, which degrades oxidized nucleotides, is one of these defense enzymes and represents a promising cancer target. We found MTH1 expression levels elevated and correlated with GBM aggressiveness and discovered that siRNA knock-down or inhibition of MTH1 with small molecules efficiently reduced viability of patient-derived GBM cultures. The effect of MTH1 loss on GBM viability was likely mediated through incorporation of oxidized nucleotides and subsequent DNA damage. We revealed that MTH1 inhibition targets GBM independent of aggressiveness as well as potently kills putative GBM stem cells in vitro. We used an orthotopic zebrafish model to confirm our results in vivo and light-sheet microscopy to follow the effect of MTH1 inhibition in GBM in real time. In conclusion, MTH1 represents a promising target for GBM therapy and MTH1 inhibitors may also be effective in patients that suffer from recurring disease.
PMID: 29156675 [PubMed]
Photodynamic inactivation of Escherichia coli - Correlation of singlet oxygen kinetics and phototoxicity.
J Photochem Photobiol B. 2017 Nov 13;178:219-227
Authors: Müller A, Preuß A, Röder B
Photodynamic inactivation (PDI) of bacteria may play a major role in facing the challenge of the ever expanding antibiotic resistances. Here we report about the direct correlation of singlet oxygen luminescence kinetics and phototoxicity in E. coli cell suspension under PDI using the widely applied cationic photosensitizer TMPyP. Through direct access to the microenvironment, the time resolved investigation of singlet oxygen luminescence plays a key role in understanding the photosensitization mechanism and inactivation pathway. Using the homemade set-up for highly sensitive time resolved singlet oxygen luminescence detection, we show that the cationic TMPyP is localized predominantly outside the bacterial cells but in their immediate vicinity prior to photodynamic inactivation. Throughout following light exposure, a clear change in singlet oxygen kinetics indicates a redistribution of photosensitizer molecules to at least one additional microenvironment. We found the signal kinetics mirrored in cell viability measurements of equally treated samples from same overnight cultures conducted in parallel: A significant drop in cell viability of the illuminated samples and stationary viability of dark controls. Thus, for the system investigated in this work - a Gram-negative model bacteria and a well-known PS for its PDI - singlet oxygen kinetics correlates with phototoxicity. This finding suggests that it is well possible to evaluate PDI efficiency directly via time resolved singlet oxygen detection.
PMID: 29156350 [PubMed - as supplied by publisher]
ABCG2-mediated suppression of chlorin e6 accumulation and photodynamic therapy efficiency in glioblastoma cell lines can be reversed by KO143.
J Photochem Photobiol B. 2017 Oct 28;178:182-191
Authors: Abdel Gaber SA, Müller P, Zimmermann W, Hüttenberger D, Wittig R, Abdel Kader MH, Stepp H
BACKGROUND: Photodynamic therapy (PDT) of malignant brain tumors is a promising adjunct to standard treatment, especially if tumor stem cells thought to be responsible for tumor progression and therapy resistance were also susceptible to this kind of treatment. However, some photosensitizers have been reported to be substrates of ABCG2, one of the membrane transporters mediating resistance to chemotherapy. Here we investigate, whether inhibition of ABCG2 can restore sensitivity to photosensitizer chlorin e6-mediated PDT.
METHODS: Accumulation of chlorin e6 in wild type U87 and doxycycline-inducible U251 glioblastoma cells with or without induction of ABCG2 expression or ABCG2 inhibition by KO143 was analyzed using flow cytometry. In U251 cells, ABCG2 was inducible by doxycycline after stable transfection with a tet-on expression plasmid. Tumor sphere cultivation under low attachment conditions was used to enrich for cells with stem cell-like properties. PDT was done on monolayer cell cultures by irradiation with laser light at 665nm.
RESULTS: Elevated levels of ABCG2 in U87 cells grown as tumor spheres or in U251 cells after ABCG2 induction led to a 6-fold lower accumulation of chlorin e6 and the light dose needed to reduce cell viability by 50% (LD50) was 2.5 to 4-fold higher. Both accumulation and PDT response can be restored by KO143, an efficient non-toxic inhibitor of ABCG2.
CONCLUSION: Glioblastoma stem cells might escape phototoxic destruction by ABCG2-mediated reduction of photosensitizer accumulation. Inhibition of ABCG2 during photosensitizer accumulation and irradiation promises to restore full susceptibility of this crucial tumor cell population to photodynamic treatment.
PMID: 29156346 [PubMed - as supplied by publisher]
Magnetic fields are causing small, but significant changes of the radiochromic EBT3 film response to 6 MV photons.
Phys Med Biol. 2017 Nov 20;:
Authors: Delfs B, Schoenfeld AA, Poppinga D, Kapsch RP, Jiang P, Harder D, Poppe B, Looe HK
The optical density (OD) of EBT3 radiochromic exposed to absorbed doses to water up to D = 20 Gy in magnetic fields of B = 0.35 and 1.42 T was measured in three colour channels. A 7 cm wide water phantom with fixed film holder was placed in magnetic fields and was irradiated by a 6 MV photon beam whose axis was directed at right angles with the field lines. The doses at the film position at water depth 5 cm were measured with a calibrated ionization chamber when the magnet was switched off and were converted to the doses in presence of the magnetic field via the monitor units and by a Monte Carlo-calculated correction accounting for the slight change of the depth dose curves in magnetic fields. In the presence of the 0.35 and 1.42 T fields small negative changes of the OD values at given absorbed doses to water occurred and significantly exceeded the uncertainty margin given by the stochastic and the uncorrected systematic deviations. This change can be described by a + 2 % change of the dose values needed to produce a given optical density in the presence of a 1.42 T field. The thereby modified OD versus D function remained unchanged irrespective whether the original short film side - the preference direction of the monomer crystals of the film - was directed parallel or orthogonal to the magnetic field. The "orientation effect" remained unaltered after EBT3 film exposure in magnetic fields. An optical bench investigation of EBT3 films exposed to doses of 10 and 20 Gy at 0.35 and 1.42 T showed that the direction of the electric vector of polarised light experiencing the largest transmission through EBT3 films remained unaltered after film exposure in the magnetic fields.
PMID: 29155691 [PubMed - as supplied by publisher]
Baicalein Inhibits Acinar-to-Ductal Metaplasia of Pancreatic Acinal Cell AR42J via Improving the Inflammatory Microenvironment.
J Cell Physiol. 2017 Nov 20;:
Authors: Pu WL, Luo YY, Bai RY, Guo AW, Zhou K, Zhang YS, Miao L, Rüegg C, Hottiger MO, Gao XM, Sun LK
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers. Recent research has demonstrated that chronic pancreatitis (CP) is associated with an increased risk of PDAC, partly due to acinar-to-ductal metaplasia (ADM). Baicalein has been shown to exert anti-inflammatory and anti-tumor effects for CP or PDAC, respectively. The aim of our study was to investigate the effect of baicalein, and the putative underlying mechanism, on inflammatory cytokines-induced ADM of rat pancreatic acinar cell line AR42J. To investigate ADM and baicalein effects in vitro, AR42J were treated with recombinant rat Tumor Necrosis Factor alpha (rTNFα) with or without baicalein for 5 days. Results showed that rTNFα-induced AR42J cells switched their phenotype from dominantly amylase-positive acinar cells to dominantly cytokeratin 19-positive ductal cells. Moreover, expression of the transcripts for TNFα or Hes-1, a Notch target, was up-regulated in these cells. Interestingly, baicalein reduced the population of ADM as well as cytokines gene expression but not Hes-1. Baicalein inhibited NF-κB activation induced by rTNFα in AR42J, but no effect on Notch 1activation. Moreover, baicalein suppressed the secretion of TNFα and Nitric Oxide (NO) in macrophages stimulated with LPS and further inhibited ADM of conditional medium-treated AR42J cells. Baicalein also suppressed the inflammatory response of LPS-activated macrophages, thereby inhibited ADM of AR42J by altering their microenvironment. Taken together, our study indicates that baicalein reduces rTNFα-induced ADM of AR42J cells by inhibiting NF-κB activation. It also sheds new light on Chinese material medica therapy of pancreatitis and thereby prevention of PDAC. This article is protected by copyright. All rights reserved.
PMID: 29155449 [PubMed - as supplied by publisher]
Photodynamic therapy in fibrosarcoma BALB/c animal model: Observation of the rebound effect.
Photodiagnosis Photodyn Ther. 2017 Nov 16;:
Authors: Eugenia EM, Ángel PM, Anabella G, Solange B, Carlos P, Horacio P, Mario G
In vivo spectrofluorometric analysis during photodynamic therapy (PDT) is a fundamental tool to obtain information about the drug bleaching kinetics. Using a portable spectrofluorometer with an excitation source emitting at 400nm wavelength and a spectral analyzer ranging from 500nm to 800nm, the evolution of the meta-tetra(hydroxyphenyl) chlorin (m-THPC) photosensitizer fluorescence spectrum at the tumoral tissue of BALB/c murines with fibrosarcoma located at their flank was followed up. Ex vivo fluorescence measurements of the tumor and skin were also performed with the aim of better characterizing the in vivo signal at different parts of the tumor. PDT was performed employing a LED 637nm light source. Fluorescence at different parts of the tumor and at the tail and armpit of mice was measured immediately after injection and followed daily. The average fluorescence intensity in the tumor reached a maximum after 24 - 72h. Subsequently, illuminations 24, 48, 72 and 96h post-injection were performed, and the fluorescence was measured immediately before and after each illumination. Eventually, 24h post-illumination, the fluorescence at certain parts of the tumor increased in comparison with that measured immediately after illumination. This effect, named "rebound effect", was due to the new local accumulation of the drug, and was used to perform a second illumination on some mice to increase the amount of photodynamic reaction and significantly improve the PDT outcome. These results are encouraging to optimize the PDT in the proposed animal model, thinking about the possible translation to humans.
PMID: 29155337 [PubMed - as supplied by publisher]
Photo-based PDT/PTT dual model killing and imaging of cancer cells using phycocyanin-polypyrrole nanoparticles.
Eur J Pharm Biopharm. 2017 Nov 14;:
Authors: Bharathiraja S, Manivasagan P, Santha Moorthy M, Bui NQ, Jang B, Phan TTV, Jung WK, Kim YM, Lee KD, Oh J
Photodynamic therapy (PDT) and photothermal therapy (PTT) using nanoparticles have gained significant attention for its therapeutic effect for cancer treatment. In the present study, we fabricated polypyrrole nanoparticles by employing bovine serum albumin-phycocyanin complex and the formulated particles were stable in various physiological solutions like water, phosphate buffered saline and culture media. The formulated nanoparticles did not cause any noticeable toxicity to MDA-MB-231 and HEK-293 cells. The obtained nanoparticles effectively killed MDA-MB-231 cells in a dual way upon laser illumination, one is through phycocyanin propagated reactive oxygen species (PDT) upon laser illumination and in another way it eradicated the treated cells by converting optical energy into heat energy (PTT). Additionally, the nanoparticles generated good amplitude of ultrasound signals under photoacoustic imaging (PAT) system that facilitates imaging of treated cells. In conclusion, the fabricated particles could be used as a multimodal therapeutic agent for treatment of cancer in the biomedical field.
PMID: 29154833 [PubMed - as supplied by publisher]
Treatment of cancer by low intensity laser radiation therapy.
Prog Biophys Mol Biol. 2017 Nov 14;:
Authors: Abo-Neima SE
Cancer treatment is one of the main challenges that face the scientific centers all over the world. The cancer incidence percentage increases year after year. The most used treatment for cancer is chemotherapy which is an application of systemic cytotoxic drug inside the patient. There are two main problems in chemotherapy that the cytotoxic drug is given systematically and cannot be localized in the tumor region in most cases that lead to killing the cancer cells as well as normal cells; and that cause the chemotherapy side effects like anemia, decrease in all blood cells count and platelets, nausea, vomiting, diarrhea, hair and nails loss and may cause a kind of blood toxicity. Photodynamic therapy (PDT) is a relatively new approach for the treatment of malignancies with only minimal side effects for the patient. It is based on the administration of a tumor-localizing dye (photosensitizer, PS) that becomes toxic to neoplastic cells when is activated by light (usually from a laser) at a specific wavelength in the presence of O2. In this work photodynamic therapy modality was used. Porphyrin derivative was used as a photo sensitizer drug and one source of energy were used; namely infrared laser with three frequency levels (1000, 2000, and 3000 Hz). Tumor-bearing animals were divided into the following groups each of 10 animals. The 1st group consists of two control groups: the 1st one was untreated group and the 2nd one was injected with photosensitizer alone. The 2nd group consists of 30 mice divided into 3 sub-groups and tumor site was irradiated with laser light as follows:1000 Hz,2000 Hz and 3000 Hz for 5 min.3rd group consists of 30 mice injected with HPD 12.5 mg/kg,then divided into 3 subgroup and tumor site was irradiated with laser light at the same conditions of 2ndgroup.The results show decrease in tumor size treated with drug (HPD) which is used as a photo sensitizer, laser, and combined treatment, both in the presence and absence of photosensitizer. Combined treatment is more effective on tumor cells than using of laser and drug alone. Also the presence of photosensitizer increases the effect of laser on tumor size. However, from histopathology of ehrlich tumor using 3000 Hz of laser irradiation in the presence of the photosensitizer drug approximately has the most effect than using the photosensitizer drug alone and exhibit totally necrotized tumor. It could be concluded that the use of the photosensitizer drug alone has no effect on the ehlrich tumor. However, the presence of the drug gave maximum effects with exposure to 3000 Hz infrared laser irradiation. The work needs to be extended to reach more and powerful effects using the photodynamic therapy with exposure to other different energies of infrared laser radiation.
PMID: 29154796 [PubMed - as supplied by publisher]
Degree of conversion of resin cement with varying methacrylate compositions used to cement fiber dowels: A Raman spectroscopy study.
J Prosthet Dent. 2017 Nov 15;:
Authors: BinMahfooz AM, Qutub OA, Marghalani TY, Ayad MF, Maghrabi AA
STATEMENT OF PROBLEM: Studies on the degree of conversion of dental cement in relation to the number of methacrylate components are lacking.
PURPOSE: The purpose of this in vitro study was to evaluate the degree of conversion of single- and multicomponent methacrylate-containing dental cements around opaque and translucent fiber dowels at varying depths.
MATERIAL AND METHODS: Teeth were prepared for standard endodontic therapy, and a dowel space was created. Opaque and translucent fiber dowels consisting of Aestheti-Plus (AP) and FiberKleer were cemented with 4 methacrylate (MA)-containing cements, including RelyX U100 (R), which contains TEGDMA; Duolink (D), which contains TEGDMA and BisGMA; and Variolink N LC (V) and Breeze (B), which contain TEGDMA, BisGMA, and UDMA. Light-emitting diode polymerization was performed for 60 seconds. The specimens were immediately cut into halves and measured within the first hour at depths of 1, 3, and 5 mm using Raman spectroscopy, and the degree of conversion (DC) of resin cement was calculated. Data were analyzed using 3-way ANOVA and the Tukey multiple comparison test (α=.05).
RESULTS: The measured dowel regions were not significantly different at various depths (P=.10). The dowel and cement types significantly influenced the degree of conversion of the cement (P<.05). The V and B cements exhibited a higher DC than D and R cements. With AP dowels, the DC of cement D was lower than that of the V, B, and R cements.
CONCLUSIONS: Within the limitations of this in vitro study, the degrees of conversion of the tested resin cements were not affected by the tested dowel depths. Higher DC was found in cement with more than 2 types of flexible MA. Opaque dowels produced a lower DC than translucent dowels.
PMID: 29153746 [PubMed - as supplied by publisher]
Polyphosphonate ligands: From synthesis to design of hybrid PEGylated nanoparticles toward phototherapy studies.
J Colloid Interface Sci. 2017 Nov 02;513:205-213
Authors: Monteil M, Moustaoui H, Picardi G, Aouidat F, Djaker N, de La Chapelle ML, Lecouvey M, Spadavecchia J
The use of phosphonate ligands to modify the nanoparticle (NPs) surface has attracted a strong interest in the last years for the design of highly functional hybrid materials. Here, we applied a methodology to synthesize bisphosphonates having functionalized PEG side chains with a specific length in order to design a novel class of hybrid nanomaterials composed by tetraphosphonate-complex-gold COOH-terminated PEG-coated NPs (Bis-PO-PEG-AuNPs). The synthetic approach consist in three steps: (1) Complexation between new phosphonate ligands (Bis PO) and tetrachloroauric acid (HAuCl4) to form gold clusters; (2) adsorption of COOH-terminated PEG molecules (PEG) onto Bis PO-Au complex; (3) reduction of metal ions in that vicinity, growth of gold particles and colloidal stabilization. The obtained snow-shape-like hybrid nanoparticles, have been characterized by ultra-violet/visible, Raman spectroscopies, and electron microscopy imaging, involving their optical properties and photothermal activity in pancreatic adenocarcinoma cancer cells (PDAC).
PMID: 29153714 [PubMed - as supplied by publisher]
Factors influencing irradiance of locally fabricated phototherapy devices in Jos, north-central Nigeria.
Trop Doct. 2017 Jan 01;:49475517740491
Authors: Diala UM, Ofakunrin AO, Toma BO, Shwe DD, Yilgwan CS, Bode-Thomas F
Locally fabricated phototherapy devices (LFPDs) are widely used in Nigeria for the treatment of neonatal jaundice. Ours was a cross-sectional observational study of all LFPDs in major hospitals in Jos between January and March 2015. We evaluated a total of 24 LFPDs. The irradiance at the level of the baby was in the range of 2-23.9 µW/cm(2)/nm. Fourteen devices had the recommended irradiance of ≥10 µW/cm(2)/nm and none had irradiance in the intensive range. Decreasing distance from the baby, presence of reflectors and increasing number of flourecent tubes significantly contributed to higher irradiance. A combination of six tubes, presence of reflectors and a distance of 10 cm from the baby produced a mean irradiance of 23.40 µW/cm(2)/nm. The irradiance of LFPDs varies widely and can be improved by simple modifications.
PMID: 29153050 [PubMed - as supplied by publisher]
An extension of a multicenter, randomized, split-face clinical trial evaluating the efficacy and safety of chromophore gel-assisted blue light phototherapy for the treatment of acne.
Int J Dermatol. 2017 Nov 20;:
Authors: Nikolis A, Fauverghe S, Scapagnini G, Sotiriadis D, Kontochristopoulos G, Petridis A, Rigopoulos D, Dessinioti C, Kalokasidis K, Antoniou C
A variety of laser/light-based devices have been reported to be effective for the treatment of acne, yet no long-term data on efficacy and safety have been published. A first 12-week clinical trial ("Main trial") recently demonstrated that the KLOX BioPhotonic System, an LED blue light device using photo-converter chromophores, can significantly improve moderate and severe facial acne vulgaris with an excellent safety profile. This Extension trial followed the Main trial, using the same BioPhotonic System, with the same dose and instructions for use, on patients having already completed treatment in the Main trial. Main objectives of this open-label long-term extension 12-week study were to evaluate the efficacy of the KLOX BioPhotonic System on the untreated hemiface during the Main trial, as well as the duration of response on the hemiface treated during the first 12-week Main trial. Despite their young age (mean age: 21.6 years) and their 12-week participation in the Main trial, 49 (54.4%) of the total number of patients who participated in the Main trial enrolled in this additional 12-week Extension trial. Baseline grading of acne was performed with the Investigator's Global Assessment (IGA) scale. For each patient, the hemiface randomly selected as a control during the Main trial received 6 weeks of treatment (twice weekly) and was then followed up for an additional 6 weeks. The first hemiface treated in the Main trial was consequently observed throughout the Extension trial, allowing for a further 12-week assessment of outcomes (total 24 weeks). In light of an additional 12 weeks of treatment on the contralateral face, the patient compliance rate was excellent, with 91.9% of the total number of patients receiving at least 80% of the treatments. Patients with a baseline IGA grade of 2 (mild) on the treated hemiface demonstrated a success rate of 58.3 and 66.7% at weeks 6 and 12, respectively. At these same time points, subjects with a baseline IGA grade of 3 (moderate) demonstrated a success rate of 81.8 and 90.0%. Patients with a baseline IGA grade of 4 (severe) demonstrated a success rate of 100% at both week 6 and week 12. When evaluating the originally treated hemifaces from the Main trial, the rate of return to baseline at 24 weeks was calculated to be 15.5%. This latter outcome confirmed the long duration of effect following treatment. The patient safety profile was also excellent, with very few related adverse events. The BioPhotonic System, which is comprised of LED blue light phototherapy and photo-converter chromophores, provides long-term efficacy and safety in the treatment of acne vulgaris, with a rate of compliance above what is generally observed in a young population of patients suffering from acne vulgaris, especially in light of sequential enrollment in a study treating one hemiface.
PMID: 29152718 [PubMed - as supplied by publisher]
An overview of the cutaneous porphyrias.
Authors: Dawe R
This is an overview of the cutaneous porphyrias. It is a narrative review based on the published literature and my personal experience; it is not based on a formal systematic search of the literature. The cutaneous porphyrias are a diverse group of conditions due to inherited or acquired enzyme defects in the porphyrin-haem biosynthetic pathway. All the cutaneous porphyrias can have (either as a consequence of the porphyria or as part of the cause of the porphyria) involvement of other organs as well as the skin. The single commonest cutaneous porphyria in most parts of the world is acquired porphyria cutanea tarda, which is usually due to chronic liver disease and liver iron overload. The next most common cutaneous porphyria, erythropoietic protoporphyria, is an inherited disorder in which the accumulation of bile-excreted protoporphyrin can cause gallstones and, rarely, liver disease. Some of the porphyrias that cause blistering (usually bullae) and fragility (clinically and histologically identical to porphyria cutanea tarda) can also be associated with acute neurovisceral porphyria attacks, particularly variegate porphyria and hereditary coproporphyria. Management of porphyria cutanea tarda mainly consists of visible-light photoprotection measures while awaiting the effects of treating the underlying liver disease (if possible) and treatments to reduce serum iron and porphyrin levels. In erythropoietic protoporphyria, the underlying cause can be resolved only with a bone marrow transplant (which is rarely justifiable in this condition), so management consists particularly of visible-light photoprotection and, in some countries, narrowband ultraviolet B phototherapy. Afamelanotide is a promising and newly available treatment for erythropoietic protoporphyria and has been approved in Europe since 2014.
PMID: 29152226 [PubMed]
Inhibition of autophagy attenuated curcumol-induced apoptosis in MG-63 human osteosarcoma cells via Janus kinase signaling pathway.
Oncol Lett. 2017 Dec;14(6):6387-6394
Authors: Zhang C, Wang LM
The present study aimed to investigate whether autophagy was triggered by curcumol and to explore the association between autophagy and apoptosis of MG-63 cells and the underlying mechanism. MG-63 cells were cultured in vitro. An MTT assay was performed to evaluate the proliferation inhibition of the MG-63 osteosarcoma cell line by curcumol. Fluorescein isothiocyanate-Annexin V/propidium iodide staining flow cytometry was performed to analyze the apoptotic rate of cells. The morphological alterations of cell nuclei were evaluated by Hoechst 33258 viable cell staining. The effects of autophagy in cells was investigated by green fluorescent protein (GFP)-light chain 3 (LC3) transfection and using a fluorescence microscope. The expression levels of LC3II, LC3I and cleaved caspase-3 and Janus kinase (JNK) signaling pathway activation were determined by western blot analysis. Cell proliferation was inhibited by curcumol in a dose- and time-dependent manner. Curcumol induced apoptosis by the caspase-dependent signaling pathway in MG-63 cells. The present study demonstrated that curcumol could induce autophagy of MG-63 cells, which was evaluated by transmission electron microscopy. Compared with the curcumol treatment alone group, the GFP-LC3-transfected green fluorescence plasmids and the LC3II/LC3I levels in cells of the curcumol and chloroquine (CQ) treatment group were upregulated, and the apoptotic ratio was downregulated following pretreatment with autophagy inhibitor CQ for 1 h. Furthermore, curcumol treatment induced phosphorylation of the JNK signaling pathway. Of note, pretreatment with the JNK inhibitor, SP600125, decreased the rates of autophagy and apoptosis, suggesting a crucial role served by the JNK signaling pathway in the activation of autophagy by curcumol. Taken together, the results of the present study suggested that activation of the JNK signaling pathway was involved in curcumol-induced autophagy. Curcumol is a novel drug for chemotherapeutic combination therapy. Curcumol demonstrated potential antitumor activities in MG-63 cells and may be used as a novel effective reagent in the treatment of osteosarcoma.
PMID: 29151904 [PubMed]
The application of antimicrobial photodynamic therapy (aPDT) in dentistry: a critical review.
Laser Phys. 2016 Dec;26(12):
Authors: Carrera ET, Dias HB, Corbi SCT, Marcantonio RAC, Bernardi ACA, Bagnato VS, Hamblin MR, Rastelli ANS
In recent years there have been an increasing number of in vitro and in vivo studies that show positive results regarding antimicrobial photodynamic therapy (aPDT) used in dentistry. These include applications in periodontics, endodontics, and mucosal infections caused by bacteria present as biofilms. Antimicrobial photodynamic therapy is a therapy based on the combination of a non-toxic photosensitizer (PS) and appropriate wavelength visible light, which in the presence of oxygen is activated to produce reactive oxygen species (ROS). ROS induce a series of photochemical and biological events that cause irreversible damage leading to the death of microorganisms. Many light-absorbing dyes have been mentioned as potential PS for aPDT and different wavelengths have been tested. However, there is no consensus on a standard protocol yet. Thus, the goal of this review was to summarize the results of research on aPDT in dentistry using the PubMed database focusing on recent studies of the effectiveness aPDT in decreasing microorganisms and microbial biofilms, and also to describe aPDT effects, mechanisms of action and applications.
PMID: 29151775 [PubMed - in process]
Impact of oral ketamine augmentation on hospital admissions in treatment-resistant depression and PTSD: a retrospective study.
Psychopharmacology (Berl). 2017 Nov 18;:
Authors: Hartberg J, Garrett-Walcott S, De Gioannis A
RATIONALE: Depressive episodes are the leading cause of mental health-related hospital admissions in Australia, and 44% of those admitted have a previous history of hospitalisations for depression (Admitted patient mental health-related care: (Australian Institute of Health and Welfare Aust Hospital Stat 2011-12, 2013). Despite numerous available antidepressant treatments, many patients do not respond to conventional therapy, having what is called 'treatment resistance' (Fava Biol Psychiatry 53:649-659, 2003). In recent years, ketamine has risen to prominence as an effective, rapidly acting antidepressant (Ketamine: a light in the darkness: Paleos and Ross 28-33, 2013). However, customary intravenous (IV) and intramuscular (IM) routes of administration and relapse rates after cessation remain barriers to more widely adopted usage.
OBJECTIVES: This study represents the largest retrospective review of patients receiving long-term oral ketamine for treatment-resistant depression and post-traumatic stress disorder (PTSD). Our purpose was to examine the safety and efficacy of oral ketamine therapy in an outpatient setting as measured by changes in hospitalisation for psychiatric episodes.
METHODS: Hospital records of 37 patients who received oral ketamine treatment were reviewed to compare the number and duration of psychiatric hospital admissions before and after treatment. Records were also screened for adverse medical events and changes in ketamine dosage over time.
RESULTS: Following treatment, inpatient hospital days were reduced by 70%, and hospital admissions were reduced by 65%. The dose of ketamine patients required was stable over time with no evidence of tolerance building. There were no serious adverse events and no long-term negative effects associated with ketamine.
CONCLUSIONS: Oral ketamine offers a promising pharmacologic adjunct to depression treatment. It may offer a more approachable alternative to IV or IM ketamine. The results warrant further investigation into the safety and efficacy of oral ketamine for psychiatric treatment.
PMID: 29151192 [PubMed - as supplied by publisher]
Comparison of pharmacodynamic effects of ticagrelor vs prasugrel in type 2 diabetes mellitus patients with coronary heart disease.
J Clin Pharm Ther. 2017 Nov 17;:
Authors: Shang LL, Guo DD, Zhao HY, Quan AJ, Cao PG
WHAT IS KNOWN AND OBJECTIVE: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of thrombotic complications. Studies have indicated that patients with T2DM have impaired clopidogrel-induced antiplatelet effect. Ticagrelor and prasugrel are two latest generation P2Y12 inhibitors with advantageous platelet inhibitory profiles. However, the pharmacodynamic differences between the two drugs in patients with T2DM remain poorly explored.
METHODS: This study, involving 140 patients with T2DM following percutaneous coronary intervention (PCI), evaluated the efficacy of aspirin upon concomitant use of prasugrel (10 mg/d) or ticagrelor (90 mg/d). Platelet reactivity was assessed by value of ADP-induced light transmittance aggregometry (LTA) and vasodilator-stimulated phosphoprotein phosphorylation-platelet reactivity index (VASP-PRI) at baseline, 7 and 30 days after randomized P2Y12 inhibitor treatment.
RESULTS: The study showed a decreased platelet reactivity after use of P2Y12 inhibitors (both P < .001). On the basis of comparison between regimens, apart from the prasugrel group having a significantly higher LTA value at the 30-day time point (P = .043), there existed no significant differences in platelet reactivity at separate time points (all P > .05). As for intragroup measurements, when compared with 7-day and 30-day time points, similar platelet reactivity was documented in the ticagrelor group (both P > .05), but LTA tests showed a significant increase with time (days 7-30) in the prasugrel group (P = .050).
WHAT IS NEW AND CONCLUSION: Although ticagrelor and prasugrel have similar platelet inhibitory effects in patients with T2DM, if a P2Y12 inhibitor is necessitated in patients with T2DM, ticagrelor might exert a more stable antiplatelet effect with 30-day short-term treatment.
PMID: 29150850 [PubMed - as supplied by publisher]
Cd271 mediates proliferation and differentiation of epidermal stem cells to support cutaneous burn wound healing.
Cell Tissue Res. 2017 Nov 18;:
Authors: Zhang M, Cao Y, Li X, Hu L, Taieb SK, Zhu X, Zhang J, Feng Y, Zhao R, Wang M, Xue W, Yang Z, Wang Y
Burn wounds can significantly reduce the quality of life of patients with respect to their physiology and psychology and can even threaten their lives. Many treatments have been proposed, including stem cell therapy but no effective method can as yet cure such damage. Our study highlights the role of Cd271 in epidermal stem cells (eSC) during the healing of burn wounds. The expression of Cd271 increases together with burn wound healing. Injection of Cd271-over-expressing eSC into wounds promotes the healing rate in a mouse burn model. Over-expression of Cd271 enhances the abilities of eSC with regard to their differentiation, proliferation and migration and even their resistance to apoptosis in vitro. These results are in accordance with a hypothesis suggesting that Cd271 promotes the healing of skin burn wounds by improving the potential of eSC for differentiation, proliferation and migration. Our findings shed light on the role of Cd271 in wound healing and may provide new therapeutic approaches for curing burn wounds of the skin.
PMID: 29150821 [PubMed - as supplied by publisher]
Urinary tract infections in neonates with unexplained pathological indirect hyperbilirubinemia: Prevalence and significance.
Pediatr Neonatol. 2017 Oct 28;:
Authors: Bahat Ozdogan E, Mutlu M, Camlar SA, Bayramoglu G, Kader S, Aslan Y
BACKGROUND: It is controversial to test for urinary tract infection (UTI) in patients with unexplained indirect hyperbilirubinemia in the first 2 weeks of life. We aimed to study the prevalence and significance of UTIs in such neonates who were requiring phototherapy.
METHODS: Subjects were 2- to 14-day-old neonates with indirect bilirubin levels above phototherapy limit with no other abnormality in their bilirubinaemia-related etiologic workup. UTI was diagnosed by 2 consecutive positive cultures obtained by catheterisation, documenting growth of >10,000 colonies of the same microorganism with consistent antibiograms. The UTI (+) patients were evaluated by renal ultrasonography (US), and some were followed up for possible recurrent UTI.
RESULTS: 262 neonates were included in the study. UTI prevalence was 12.2%, and bacteraemia was 6.2% among UTI (+) patients. The two most common pathogens (81.2%) were Escherichiacoli and Klebsiella. pneumonia. All UTI (+) patients had undergone US, revealing 12.5% pelvicaliectasis, other 12.5% increased renal parenchymal echogenicity, 3.1% concurrent pelvicaliectasis and increased renal parenchymal echogenicity. 53.1% of UTI (+) patients had undergone follow-up, after which 23.5% recurrent UTI were found at the end of a mean of 52 months.
CONCLUSION: We suggest that the neonates with unexplained pathological jaundice should be tested for possible UTI. Consequently, all newborns with UTI shall be evaluated by the urinary US and followed up for recurrent UTI.
PMID: 29150336 [PubMed - as supplied by publisher]
ATAD2 in cancer: a pharmacologically challenging but tractable target.
Expert Opin Ther Targets. 2017 Nov 23;:1-12
Authors: Hussain M, Zhou Y, Song Y, Hameed HMA, Jiang H, Tu Y, Zhang J
INTRODUCTION: ATAD2 protein is an emerging oncogene that has strongly been linked to the etiology of multiple advanced human cancers. Therapeutically, despite the fact that genetic suppression/knockdown studies have validated it as a compelling drug target for future therapeutic development, recent druggability assessment data suggest that direct targeting of ATAD2's bromodomain (BRD) may be a very challenging task. ATAD2's BRD has been predicted as a 'difficult to drug' or 'least druggable' target due to the concern that its binding pocket, and the areas around it, seem to be unfeasible for ligand binding. Areas covered: In this review, after shedding light on the multifaceted roles of ATAD2 in normal physiology as well as in cancer-etiology, we discuss technical challenges rendered by ATAD2's BRD active site and the recent drug discovery efforts to find small molecule inhibitors against it. Expert opinion: The identification of a novel low-nanomolar semi-permeable chemical probe against ATAD2's BRD by recent drug discovery campaign has demonstrated it to be a pharmacologically tractable target. Nevertheless, the development of high quality bioavailable inhibitors against ATAD2 is still a pending task. Moreover, ATAD2 may also potentially be utilized as a promising target for future development of RNAi-based therapy to treat cancers.
PMID: 29148850 [PubMed - as supplied by publisher]
Ambient Aqueous Synthesis of Ultrasmall Ni0.85Se Nanoparticles for Noninvasive Photoacoustic Imaging and Combined Photothermal-Chemotherapy of Cancer.
ACS Appl Mater Interfaces. 2017 Nov 22;:
Authors: Wang X, Li F, Yan X, Ma Y, Miao ZH, Dong L, Chen H, Lu Y, Zha Z
Large-size-induced long-term retention in the body has hampered the translational applications of many reported nanomedicines. Herein, we reported a multifunctional theranostic agent composed of ultrasmall poly(acrylic acid)-functionalized Ni0.85Se nanoparticles (PAA-Ni0.85Se NPs), which were successfully obtained through a facile ambient aqueous precipitation strategy. Without exhibiting any noticeable toxicity, the as-prepared PAA-Ni0.85Se NPs (average diameter of 6.40 ± 1.89 nm) showed considerable absorption in near-infrared (NIR) region and high photothermal conversion efficiency of 54.06%, which could induce remarkable photoacoustic signals for tumor imaging and heat for localized ablation of cancerous cells upon exposure to NIR light. Notably, the ultrasmall PAA-Ni0.85Se NPs, unlike conventional nanomaterials with larger sizes, showed reasonable body clearance within 8 h after intravenous injection. Furthermore, ascribed to protonation process of amino groups in DOX molecules and carboxyl groups in PAA molecules in an acidic microenvironment, the drug-loaded (doxorubicin hydrochloride, DOX·HCl) PAA-Ni0.85Se NPs (PAA-Ni0.85Se-DOX NPs) revealed promoted drug release at acidic pH, which could be useful for acidic tumor microenvironment responsive drug delivery. Evident from the results of cell-killing assay in vitro and tumor treatment study in vivo, PAA-Ni0.85Se-DOX NPs exhibited evident synergistic effects on killing 4T1 breast cancer cells. Thus, this study presents a multifunctional theranostic agent composed of ultrasmall PAA-Ni0.85Se NPs for potential cancer treatment without long-term toxicity concerns.
PMID: 29148694 [PubMed - as supplied by publisher]
Proceedings of the 2017 ISEV symposium on "HIV, NeuroHIV, drug abuse, & EVs".
J Neurovirol. 2017 Nov 16;:
Authors: Hu G, Yelamanchili S, Kashanchi F, Haughey N, Bond VC, Witwer KW, Pulliam L, Buch S
Despite the success of combination antiretroviral therapy (cART), there is increased prevalence of HIV-associated neurocognitive disorders (HAND) in HIV-1-infected individuals on cART, which poses a major health care challenge. Adding further complexity to this long-term antiretroviral use is the comorbidity with drugs of abuse such as morphine, cocaine, and methamphetamine, which can in turn, exacerbate neurologic and cognitive deficits associated with HAND. Furthermore, HIV proteins, such as the transactivator of transcription (Tat) and the envelope protein (gp120), as well as antiretrovirals themselves can also contribute to the progression of neurodegeneration underlying HAND. In the field of NeuroHIV and drug addiction, EVs hold the potential to serve as biomarkers of cognitive dysfunction, targets of therapy, and as vehicles for therapeutic delivery of agents that can ameliorate disease pathogenesis. Based on the success of a previous Satellite Symposium in 2015 at the ISEV meeting in Washington, experts again expanded on their latest research findings in the field, shedding light on the emerging trends in the field of Extracellular Vesicle (EV) biology in NeuroHIV and drug abuse. The satellite symposium sought to align experts in the fields of NeuroHIV and drug abuse to share their latest insights on the role of EVs in regulating neuroinflammation, neurodegeneration, peripheral immune response, and HIV latency in HIV-infected individuals with or without the comorbidity of drug abuse.
PMID: 29147885 [PubMed - as supplied by publisher]
Advanced sensing, imaging, and therapy nanoplatforms based on Nd(3+)-doped nanoparticle composites exhibiting upconversion induced by 808 nm near-infrared light.
Nanoscale. 2017 Nov 17;:
Authors: Chan MH, Liu RS
Malignant tumors are currently the leading cause of death worldwide, followed by cardiovascular and cerebrovascular diseases. Although various methods, such as blood examination, tissue biopsy, and radiography, for tumor detection, exist, these techniques still require further refinement. Researchers have recently explored the use of novel adjuvant methods, specifically luminescence imaging detection, for the detection of tumors. The light-triggered approach is less invasive and induces fewer side effects than traditional detection methods. This paper highlights recent advances in the design, property tuning, and applications of nanoparticles that exhibit upconversion under 808 nm excitation. When doped with neodymium ions, upconverted nanoparticles gain the ability to absorb 808 nm light. The advantageous unique features of 808 nm light include deep tissue penetration and limited thermal side effects. The 808 nm-excited upconverted nanoparticles exhibit superior potential for use in biosensing, bioimaging, therapy, and three-dimensional display. Thus, innovative theranostic nanoplatforms can be developed by incorporating 808 nm-excited upconverted nanoparticles with phototherapy agents. Such a composite technique is expected to possess the individual advantages of each material.
PMID: 29147708 [PubMed - as supplied by publisher]
Sonophotodynamic therapy mediated by liposomal zinc phthalocyanine in a colon carcinoma tumor model: Role of irradiating arrangement.
Iran J Basic Med Sci. 2017 Oct;20(10):1088-1092
Authors: Bakhshizadeh M, Moshirian T, Esmaily H, Rajabi O, Nassirli H, Sazgarnia A
Objectives: Low penetration depth of light is the main defect of photodynamic therapy (PDT), which could be improved by sonodynamic therapy (SDT). In this study, a combination of PDT and SDT known as sonophotodynamic therapy (SPDT) was investigated using two reverse arrangements in CT26 tumor model.
Materials and Methods: The liposomal zinc phthalocyanine was synthesized and characterized. It was then administered to CT26 tumor models as a sensitizer. The animal models were subjected to PDT, SDT, and the combined treatment in different groups. The doubling time for the survival of tumors and animals was considered as a measure to evaluate treatments efficacy.
Results: In all treatment groups there was a significant decline in tumor volume 15 days after treatment compared to the main control group, but the optimum response was observed in the group receiving a combined treatment with the priority of PDT. 120 days after treatment, in the groups treated by PDT and SDT, the tumor shrank by 20%, while in the group receiving SPDT with PDT priority, 80% of tumors was recovered. No case of complete tumor progression was observed in SPDT group with SDT priority. This could be due to the pores created in cell membranes during ultrasound irradiation of the tumor, which removed the sensitizer molecules from the cells and reduced PDT efficacy in SPDT group with SDT priority.
Conclusion: It seems that SPDT with PDT priority offers a more efficient alternative than each of PDT, SDT individually or SPDT with the reverse arrangement.
PMID: 29147483 [PubMed]
Insecticide-treated nets and malaria prevalence, Papua New Guinea, 2008-2014.
Bull World Health Organ. 2017 Oct 01;95(10):695-705B
Authors: Hetzel MW, Pulford J, Ura Y, Jamea-Maiasa S, Tandrapah A, Tarongka N, Lorry L, Robinson LJ, Lilley K, Makita L, Siba PM, Mueller I
Objective: To investigate changes in malaria prevalence in Papua New Guinea after the distribution of long-lasting Insecticide-treated nets, starting in 2004, and the introduction of artemisinin-based combination therapy in 2011.
Methods: Two malaria surveys were conducted in 2010-2011 and 2013-2014. They included 77 and 92 randomly selected villages, respectively. In each village, all members of 30 randomly selected households gave blood samples and were assessed for malaria infection by light microscopy. In addition, data were obtained from a malaria survey performed in 2008-2009.
Results: The prevalence of malaria below 1600 m in altitude decreased from 11.1% (95% confidence interval, CI: 8.5-14.3) in 2008-2009 to 5.1% (95% CI 3.6-7.4) in 2010-2011 and 0.9% (95% CI 0.6-1.5) in 2013-2014. Prevalence decreased with altitude. Plasmodium falciparum was more common than P. vivax overall, but not everywhere, and initially the prevalence of P. vivax infection decreased more slowly than P. falciparum infection. Malaria infections were clustered in households. In contrast to findings in 2008-2009, no significant association between net use and prevalence was found in the later two surveys. The prevalence of both fever and splenomegaly also decreased but their association with malaria infection became stronger.
Conclusion: Large-scale insecticide-treated net distribution was associated with an unprecedented decline in malaria prevalence throughout Papua New Guinea, including epidemic-prone highland areas. The decline was accompanied by broader health benefits, such as decreased morbidity. Better clinical management of nonmalarial fever and research into residual malaria transmission are required.
PMID: 29147042 [PubMed - in process]
Stable ICG-loaded upconversion nanoparticles: silica core/shell theranostic nanoplatform for dual-modal upconversion and photoacoustic imaging together with photothermal therapy.
Sci Rep. 2017 Nov 16;7(1):15753
Authors: Lv R, Wang D, Xiao L, Chen G, Xia J, Prasad PN
We report here the design and multiple functions of a new hierarchical nanotheronostic platform consisting of an upconversion nanoparticle (UCNP) core: shell with an additional mesoporous silica (mSiO2) matrix load shell containing sealed, high concentration of ICG molecules. We demonstrate that this UCNP@mSiO2-ICG nanoplatform can perform the following multiple functions under NIR excitation at 800 nm: 1) Light harvesting by the UCNP shell containing Nd and subsequent energy transfer to Er in the Core to produce efficient green and red upconversion luminescence for optical imaging; 2) Efficient nonradiative relaxation and local heating produced by concentration quenching in aggregated ICG imbedded in the mesopourous silica shell to enable both photoacoustic imaging and photothermal therapy. Compared to pure ICG, sealing of mesoporous silica platforms prevents the leak-out and improves the stability of ICG by protecting from rapid hydrolysis. Under 800 nm laser excitation, we performed both optical and photoacoustic (PA) imaging in vitro and in vivo. Our results demonstrated that UCNP@mSiO2-ICG with sealed structures could be systemically delivered to brain vessels, with a long circulation time. In addition, these nanoplatforms were capable of producing strong hyperthermia efforts to kill cancer cells and hela cells under 800 nm laser irradiation.
PMID: 29147000 [PubMed - in process]
Specific Targeting of Melanotic Cells with Peptide Ligated Photosensitizers for Photodynamic Therapy.
Sci Rep. 2017 Nov 16;7(1):15750
Authors: Bigliardi PL, Rout B, Pant A, Krishnan-Kutty V, Eberle AN, Srinivas R, Burkett BA, Bigliardi-Qi M
A strategy combining covalent conjugation of photosensitizers to a peptide ligand directed to the melanocortin 1 (MC1) receptor with the application of sequential LED light dosage at near-IR wavelengths was developed to achieve specific cytotoxicity to melanocytes and melanoma (MEL) with minimal collateral damage to surrounding cells such as keratinocytes (KER). The specific killing of melanotic cells by targeted photodynamic therapy (PDT) described in this study holds promise as a potentially effective adjuvant therapeutic method to control benign skin hyperpigmentation or superficial melanotic malignancy such as Lentigo Maligna Melanoma (LMM).
PMID: 29146972 [PubMed - in process]
Biological treatments in giant cell arteritis & Takayasu arteritis.
Eur J Intern Med. 2017 Nov 13;:
Authors: Samson M, Espígol-Frigolé G, Terrades-García N, Prieto-González S, Corbera-Bellalta M, Alba-Rovira R, Hernández-Rodríguez J, Audia S, Bonnotte B, Cid MC
Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are the two main large vessel vasculitides. They share some similarities regarding their clinical, radiological and histological presentations but some pathogenic processes in GCA and TAK are activated differently, thus explaining their different sensitivity to biological therapies. The treatment of GCA and TAK essentially relies on glucocorticoids. However, thanks to major progress in our understanding of their pathogenesis, the role of biological therapies in the treatment of these two vasculitides is expanding, especially in relapsing or refractory diseases. In this review, the efficacy, the safety and the limits of the main biological therapies ever tested in GCA and TAK are discussed. Briefly, anti TNF-α agents appear to be effective in treating TAK but not GCA. Recent randomized placebo-controlled trials have reported on the efficacy and safety of abatacept and mostly tocilizumab in inducing and maintaining remission of GCA. Abatacept was not effective in TAK and robust data are still lacking to draw any conclusions concerning the use of tocilizumab in TAK. Furthermore, ustekinumab appears promising in relapsing/refractory GCA whereas rituximab has been reported to be effective in only a few cases of refractory TAK patients. If a biological therapy is indicated, and in light of the data discussed in this review, the first choice would be tocilizumab in GCA and anti-TNF-α agents (mainly infliximab) in TAK.
PMID: 29146018 [PubMed - as supplied by publisher]
Study on the adverse effects following chemotherapy for breast cancer diagnosis during pregnancy: The first case report in China.
Medicine (Baltimore). 2017 Nov;96(46):e8582
Authors: Ye X, He Q, Zhou X
RATIONALE: Treatment of breast cancer during pregnancy (BCP) remains a challenge to physicians. Surgery and chemotherapy during pregnancy are widely used for the treatment of BCP. Herein, we reported 3 Chinese patients with BCP who underwent chemotherapy during pregnancy and were followed up for adverse effects.
PATIENT CONCERNS: Three female patients (case 1, case 2, and case 3) of 37-, 32-, and 28-year-old with breast masses were enrolled. Case 1 had been pregnant for over 4 months, case 2 over 7 months, and case 3 for 7 months. Ultrasound findings revealed a mass in the left breast in cases 1 and 2 (30 mm × 26 mm × 23 mm and 34 mm × 16 mm × 40 mm), and case 3 had 2 masses in the outer upper quadrant of right breast (27 mm × 27 mm × 26 mm, 18 mm × 17 mm × 17 mm) and 2 fixed enlarged lymph nodes in the right axillary fossa, respectively.
DIAGNOSES: All breast masses were diagnosed by core needle biopsy, and the result was infiltrating ductal carcinoma.
INTERVENTIONS: Chemotherapy regimen administered during pregnancy was EwP (epirubicin 80 mg/m, d1 + paclitaxel 80 mg/m, d1, 8, 15, and cycled every 21 days). During pregnancy, case 1 received 5 cycles, case 2 received 1 cycle, and case 3 received 2 cycles.
OUTCOMES: Case 2 patient experienced grade III bone marrow suppression once. Electrocardiogram (ECG) result of case 3 showed occasional occurrence of ventricular premature beats, with no complaint of discomfort. All 3 patients experienced uterine contractions, which caused preterm labor in case 2. Adverse events were nausea, hair loss, acid reflux, and constipation. Neonatal jaundice occurred in the premature infant (case 2), which was resolved by phototherapy. No relapse or metastasis was observed in the 3 cases and the infants are growing normally.
LESSONS: Both patients and infants well tolerated the combination chemotherapy of epirubicin and paclitaxel during pregnancy. There were few drug toxicities and adverse effects.
PMID: 29145270 [PubMed - in process]
Gold-chlorophyll a-hybrid nanoparticles and chlorophyll a/cetyltrimethylammonium chloride self-assembled-suprastructures as novel carriers for chlorophyll a delivery in water medium: Photoactivity and photostability.
Colloids Surf B Biointerfaces. 2017 Nov 09;161:555-562
Authors: Rizzi V, Vurro D, Placido T, Fini P, Petrella A, Semeraro P, Cosma P
The stability of Chlorophyll a in water during prolonged exposure, at room temperature, to a neon lamp has been investigated by means of UV-vis and fluorescence spectroscopies. In addition, the Chlorophyll a (photo)stability evaluation in presence of suitable carriers has been performed in order to investigate its reactivity under the same conditions, for possible and future applications in Antimicrobial Photodynamic Therapy. Cetyltrimethylammonium chloride was chosen to solubilize Chlorophyll a in water. While, cetyltrimethylammonium chloride-capped gold nanoparticles offer a great opportunity because combine the Chlorophyll a action, used as a photosensitizer in Antimicrobial Photodynamic Therapy, with gold nanoparticles effect used in photothermal therapy. Indeed, the latter ones have exhibited an interesting rise of temperature if irradiated with visible light. Overall, both examined systems, cetyltrimethylammonium chloride/Chlorophyll a and gold nanoparticles/Chlorophyll a, were able to induce the Reactive Oxygen Species formation fundamental for a potential application in Antimicrobial Photodynamic Therapy.
PMID: 29145103 [PubMed - as supplied by publisher]
Stability of the diagnosis of seasonal affective disorder in a long-term prospective study.
J Affect Disord. 2017 Nov 07;227:353-357
Authors: Cléry-Melin ML, Gorwood P, Friedman S, Even C
BACKGROUND: Seasonal affective disorder (SAD) is mainly characterized by a seasonal pattern of depressive recurrences over the years. However, few studies have been conducted on the long-term course of patients with SAD, whose findings raised questions about the diagnosis stability over time. This study aimed to better characterize the diagnosis evolution, and determine prognosis markers.
METHODS: An initial cohort of 225 outpatients diagnosed as having a SAD, was assessed at baseline (T1) for clinical symptoms and response to bright light therapy. One hundred and nineteen patients (53%) were interviewed 2-12 years after (T2).
RESULTS: Of 119 patients reached at follow-up (T2), only 32 patients (27%) still fulfilled the DSM-IV criteria for a stable SAD (S-SAD). A large proportion (59%) of the follow up cohort was in remission and 14% still suffered from a non-seasonal mood disorder. Family history of depression, previous suicide attempt, carbohydrate craving and HAD-depression score at baseline were associated with a stable SAD (S-SAD) diagnosis at T2, the HAD-depression score being the only one still significantly predictive (p=0.025) of a later stable SAD, with a multivariate approach. Carbohydrate craving, a core symptom of SAD, showed a trend (p=0.100) to predict diagnosis stability.
LIMITATIONS: Only 53% patients from the initial cohort were assessed at follow-up.
CONCLUSIONS: Patients with eventual stable SAD show more subjective severity (higher HAD-Depression score) and carbohydrate craving at baseline. A low predictive validity of diagnosis criteria suggests that SAD is a temporary expression of a mood disorder rather than a specific disorder.
PMID: 29145077 [PubMed - as supplied by publisher]
Albumin-coordinated assembly of clearable platinum nanodots for photo-induced cancer theranostics.
Biomaterials. 2017 Oct 20;154:248-260
Authors: Tang Y, Yang T, Wang Q, Lv X, Song X, Ke H, Guo Z, Huang X, Hu J, Li Z, Yang P, Yang X, Chen H
Photoactive noble metal nanoparticles are of increasing importance toward personalized cancer therapy in the field of precision nanomedicine. A critical challenge remains in the exploration of clinically potential noble metal nanoparticles for highly efficient cancer theranostics. Here, we introduce albumin-coordinated assembly of clearable Pt nanodots (Pt-NDs) with monodisperse nanostructure as high-performance theranostic agents for imaging-guided photothermal tumor ablation. We precisely manipulate the reduction and growth of tetravalent Pt ions into ultrasmall nanodots through albumin-directed growth kinetics, thereby leading to the synthesis of monodisperse 6.7 nm Pt-NDs with albumin molecules as the corona. Pt-NDs exhibit the surface plasmon resonance at 225 nm with enhanced near-infrared (NIR) absorbance, ideal resistance to photo-bleaching, distinct photoacoustic and X-ray signals, as well as remarkable photothermal effect through non-radiative relaxation under NIR light irradiation. In particular, Pt-NDs possess preferable tumor accumulation, and effective in vivo excretory capability. Thus, these nanodots promote preferable in vivo microscopic photoacoustics and spatially anatomic CT imaging with enhanced contrast, as well as potent hyperthermia-mediated tumor ablation. These findings represent a facile and general approach to fabricate high-performance noble metal nanostructures with clinical potential for cancer theranostics.
PMID: 29144983 [PubMed - as supplied by publisher]
Disruptions in sleep-wake cycles in community-dwelling cancer patients receiving palliative care and their correlates.
Chronobiol Int. 2017 Nov 16;:1-14
Authors: Bernatchez MS, Savard J, Ivers H
Significant disruptions in sleep-wake cycles have been found in advanced cancer patients in prior research. However, much remains to be known about specific sleep-wake cycle variables that are impaired in patients with a significantly altered performance status. More studies are also needed to explore the extent to which disrupted sleep-wake cycles are related to physical and psychological symptoms, time to death, maladaptive sleep behaviors, quality of life and 24-h light exposure. This study conducted in palliative cancer patients was aimed at characterizing patients' sleep-wake cycles using various circadian parameters (i.e. amplitude, acrophase, mesor, up-mesor, down-mesor, rhythmicity coefficient). It also aimed to compare rest-activity rhythm variables of participants with a performance status of 2 vs. 3 on the Eastern Cooperative Oncology Group scale (ECOG) and to evaluate the relationships of sleep-wake cycle parameters with several possible correlates. The sample was composed of 55 community-dwelling cancer patients receiving palliative care with an ECOG of 2 or 3. Circadian parameters were assessed using an actigraphic device for seven consecutive 24-h periods. A light recording and a daily pain diary were completed for the same period. A battery of self-report scales was also administered. A dampened circadian rhythm, a low mean activity level, an early mean time of peak activity during the day, a late starting time of activity during the morning and an early time of decline of activity during the evening were observed. In addition, a less rhythmic sleep-wake cycle was associated with a shorter time to death (from the first home visit) and with a lower 24-h light exposure. Sleep-wake cycles are markedly disrupted in palliative cancer patients, especially, near the end of life. Effective non-pharmacological interventions are needed to improve patients' circadian rhythms, including perhaps bright light therapy.
PMID: 29144172 [PubMed - as supplied by publisher]
Perspective on the real-life use of phototherapy in early stage Mycosis Fungoides from the Cutaneous Lymphoma commission of Fondazione Italiana Linfomi: results from a web-based survey.
G Ital Dermatol Venereol. 2017 Nov 16;:
Authors: Grandi V, Fava P, Rupoli S, Violetti SA, Canafoglia L, Berti E, Quaglino P, Fondazione Italiana Linfomi
PMID: 29144101 [PubMed - as supplied by publisher]
Cell Death Pathways Associated with Photodynamic Therapy: an Update.
Photochem Photobiol. 2017 Nov 16;:
Authors: Kessel D, Oleinick NL
Photodynamic therapy (PDT) has the potential to make a significant impact on cancer treatment. PDT can sensitize malignant tissues to light, leading to a highly selective effect if an appropriate light dose can be delivered. Variations in light distribution and drug delivery, along with impaired efficacy in hypoxic regions, can reduce the overall tumor response. There is also evidence that malignant cells surviving PDT may become more aggressive than the initial tumor population. Promotion of more effective direct tumor eradication is therefore an important goal. While a list of properties for the 'ideal' photosensitizing agent often includes formulation, pharmacologic and photophysical elements, we propose that sub-cellular targeting is also an important consideration. Perspectives relating to optimizing PDT efficacy are offered here. These relate to death pathways initiated by photodamage to particular sub-cellular organelles. This article is protected by copyright. All rights reserved.
PMID: 29143339 [PubMed - as supplied by publisher]
Investigation of arginine A-specific cysteine proteinase gene expression profiling in clinical Porphyromonas gingivalis isolates against photokilling action of the photo-activated disinfection.
Lasers Med Sci. 2017 Nov 15;:
Authors: Pourhajibagher M, Ghorbanzadeh R, Bahador A
Porphyromonas gingivalis is a significant root canal pathogen capable of causing endodontic infections, which during their treatment may receive sub-lethal doses of photo-activated disinfection (sPAD). As sPAD can influence microbial virulence, this study was designed to evaluate the effect of sPAD on gene expression level of arginine A-specific cysteine proteinase (rgpA), as one of the underlying virulence factors involved in the development of endodontic infection via P. gingivalis strains. To find out the sPAD against 16 clinical isolates of PAD-resistant P. gingivalis that were isolated in vivo, we used toluidine blue O (TBO), methylene blue (MB), and indocyanine green (ICG) as the photosensitizers, which were excited with specific wavelength of light in vitro. Quantitative real-time PCR (qRT-PCR) was then applied to monitor gene expression of rgpA in P. gingivalis isolates to characterize its virulence agent and understand the effect of sPAD on its pathogenicity. Maximal sPAD that could not decrease the count of P. gingivalis isolates were 6.25, 15.6, and 25 μg/mL at fluencies of 171.87, 15.6, and 93.75 J/cm(2) for TBO, ICG, and MB, respectively. ICG-sPAD could suppress the rgpA gene expression about 14-fold, while MB and TBO-mediated sPAD could cause the attenuation of rgpA expression about 4.9- and 11.6-fold, respectively. ICG-sPAD with the maximum ability to reduce rgpA gene expression compared with other photosensitizers can be an appropriate candidate for the treatment of endodontic infections.
PMID: 29143136 [PubMed - as supplied by publisher]
Advanced smart-photosensitizers for more effective cancer treatment.
Biomater Sci. 2017 Nov 16;:
Authors: Park W, Cho S, Han J, Shin H, Na K, Lee B, Kim DH
Photodynamic therapy (PDT) based upon the use of light and photosensitizers (PSs) has been used as a novel treatment approach for a variety of tumors. It, however, has several major limitations in the clinic: poor water solubility, long-term phototoxicity, low tumor targeting efficacy, and limited light penetration. With advances in nanotechnology, materials science, and clinical interventional imaging procedures, various smart-PSs have been developed for improving their cancer-therapeutic efficacy while reducing the adverse effects. Here, we briefly review state-of-the-art smart-PSs and discuss the future directions of PDT technology.
PMID: 29142997 [PubMed - as supplied by publisher]
Extraordinary clinical benefit to sequential treatment with targeted therapy and immunotherapy of a BRAF V600E and PD-L1 positive metastatic lung adenocarcinoma.
Exp Hematol Oncol. 2017;6:29
Authors: Li SD, Martial A, Schrock AB, Liu JJ
Background: The treatment algorithm for metastatic non-small cell lung cancers (NSCLCs) has been evolving rapidly due to the development of new therapeutic agents. Although guidelines are provided by National Comprehensive Cancer Network (NCCN) for treatment options according to biomarker testing results, sequentially applying the three main modalities (chemotherapy, targeted therapy and immunotherapy) remains an ad hoc practice in clinic. In light of recent FDA approval of dabrafenib and trametinib combination for metastatic NSCLCs with BRAF V600E mutation, one question arises due to insufficient clinical data is if the targeted therapy should be used before immunotherapy in patients with both BRAF V600E and PD-L1 expression.
Case presentation: We present a case of 74-year-old female, former smoker with metastatic lung adenocarcinoma. The BRAF V600E mutation among other abnormalities was identified by comprehensive genomic profiling. The patient had an excellent 2-year response to the combination of pemetrexed and sorafenib. The patient was then treated with dabrafenib due to the presence of the BRAF V600E mutation and intolerance to cytotoxic chemotherapy. Not only the patient had an 18-month durable response to dabrafenib, she experienced outstanding quality of life with no serious adverse effects. At the time of symptomatic progression, the patient was then treated with two cycles of pembrolizumab based on her positive PD-L1 staining (90%). She had early response and came off pembrolizumab due to side effects. Seven months after initiation of pembrolizumab, the patient is off all the therapy and is currently asymptomatic. The patient is surviving with metastatic disease for over 7 years as of to date.
Conclusions: By appropriately sequencing the three main modalities of systemic therapies, we are able to achieve long-term disease control with minimal side effects even in a geriatric patient with multiple comorbidities. We argue that it is reasonable to first use a BRAF inhibitor before considering immunotherapy for NSCLCs positive for both BRAF V600E and PD-L1.
PMID: 29142786 [PubMed]
Proteotoxicity in cardiac amyloidosis: amyloidogenic light chains affect the levels of intracellular proteins in human heart cells.
Sci Rep. 2017 Nov 15;7(1):15661
Authors: Imperlini E, Gnecchi M, Rognoni P, Sabidò E, Ciuffreda MC, Palladini G, Espadas G, Mancuso FM, Bozzola M, Malpasso G, Valentini V, Palladini G, Orrù S, Ferraro G, Milani P, Perlini S, Salvatore F, Merlini G, Lavatelli F
AL amyloidosis is characterized by widespread deposition of immunoglobulin light chains (LCs) as amyloid fibrils. Cardiac involvement is frequent and leads to life-threatening cardiomyopathy. Besides the tissue alteration caused by fibrils, clinical and experimental evidence indicates that cardiac damage is also caused by proteotoxicity of prefibrillar amyloidogenic species. As in other amyloidoses, the damage mechanisms at cellular level are complex and largely undefined. We have characterized the molecular changes in primary human cardiac fibroblasts (hCFs) exposed in vitro to soluble amyloidogenic cardiotoxic LCs from AL cardiomyopathy patients. To evaluate proteome alterations caused by a representative cardiotropic LC, we combined gel-based with label-free shotgun analysis and performed bioinformatics and data validation studies. To assess the generalizability of our results we explored the effects of multiple LCs on hCF viability and on levels of a subset of cellular proteins. Our results indicate that exposure of hCFs to cardiotropic LCs translates into proteome remodeling, associated with apoptosis activation and oxidative stress. The proteome alterations affect proteins involved in cytoskeletal organization, protein synthesis and quality control, mitochondrial activity and metabolism, signal transduction and molecular trafficking. These results support and expand the concept that soluble amyloidogenic cardiotropic LCs exert toxic effects on cardiac cells.
PMID: 29142197 [PubMed - in process]
Light-Responsive Nanoparticles for Highly Efficient Cytoplasmic Delivery of Anticancer Agents.
ACS Nano. 2017 Nov 20;:
Authors: Wang Y, Deng Y, Luo H, Zhu A, Ke H, Yang H, Chen H
Stimuli-responsive nanostructures have shown great promise for intracellular delivery of anticancer compounds. A critical challenge remains in the exploration of stimuli-responsive nanoparticles for fast cytoplasmic delivery. Herein, near-infrared (NIR) light-responsive nanoparticles were rationally designed to generate highly efficient cytoplasmic delivery of anticancer agents for synergistic thermo-chemotherapy. The drug-loaded polymeric nanoparticles of selenium-inserted copolymer (I/D-Se-NPs) were rapidly dissociated in several minutes through reactive oxygen species (ROS)-mediated selenium oxidation upon NIR light exposure, and this irreversible dissociation of I/D-Se-NPs upon such a short irradiation promoted continuous drug release. Moreover, I/D-Se-NPs facilitated cytoplasmic drug translocation through ROS-triggered lysosomal disruption and thus resulted in highly preferable distribution to the nucleus even in 5 min postirradiation, which was further integrated with light-triggered hyperthermia for achieving synergistic tumor ablation without tumor regrowth.
PMID: 29141151 [PubMed - as supplied by publisher]
A Water-Soluble Galactose-Decorated Cationic Photodynamic Therapy Agent Based on BODIPY to Selectively Eliminate Biofilm.
Biomacromolecules. 2017 Nov 15;:
Authors: Dai X, Chen X, Zhao Y, Yu Y, Wei X, Zhang X, Li C
A multitude of serious chronic infections involved in bacterial biofilms that are difficult to eradicate. Here, a water-soluble galactose functionalized cationic 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-based photodynamic therapy agent was synthesized for selectively eliminating the bacterial biofilm. These conjugates can capture bacteria to form aggregations through electrostatic interaction and then generate a large number of reactive oxygen species (ROS) under visible light irradiation to kill the bacteria without the emergence of bacterial resistance. Simultaneously, this agent could effectively inhibit and eradicate both Gram-positive and Gram-negative bacterial biofilms. The in-depth analysis of antimicrobial mechanism confirmed that the conjugates can quickly bind on the bacterial surface, irreversible disrupt the bacterial membrane, distinctly inhibit intracellular enzyme activity, ultimately leading to the bacterial death. Importantly, these conjugates are highly selectivity toward bacterial cells over mammalian cells as well as no cytotoxicity to A549 cells and no discernible hemolytic activity. Collectively, this water-soluble galactose-decorated cationic BODIPY-based photodynamic therapy agent design provides promising insights for the development of therapy for antibiotic-resistant bacteria.
PMID: 29141147 [PubMed - as supplied by publisher]
Lasers, Light, and the Treatment of Acne: A Comprehensive Review of the Literature.
J Drugs Dermatol. 2017 Nov 01;16(11):1095-1102
Authors: Tong LX, Brauer JA
INTRODUCTION: Acne vulgaris is common dermatologic condition with an estimated prevalence of 70 to 87%. Acne has been shown to have a significant impact on patient quality of life and mental health, especially as inflammatory lesions typically occur on cosmetically sensitive areas with the potential for permanent scarring. There have been numerous advances in the treatment of inflammatory acne with light-based and laser devices.
OBJECTIVE: To review the current evidence for light-based and laser treatments in the management of inflammatory acne.
METHODS: An analysis was conducted of PubMed indexed English language literature regarding management of inflammatory acne using light-based and laser treatments.
RESULTS: Evidence for the utilization of laser and light-based therapy for acne was summarized in a comprehensive review. Laser and light-based treatment holds the advantages of improved patient compliance and safety profiles in comparison to pharmacologic therapy. Efficacy of device based treatment varied in comparison to standard topical treatment regimens, often more effective when used in combination therapy. Adverse effects reported were generally self-limited.
DISCUSSION: These treatments do and will continue to play an important and enlarging role in the management of acne. Larger scale studies with standardization of treatment protocols are warranted. <p><em>J Drugs Dermatol. 2017;16(11):1095-1102.</em></p>.
PMID: 29141057 [PubMed - in process]
Evidence to Use Botulinum Toxin Injections in Tension-Type Headache Management: A Systematic Review.
Toxins (Basel). 2017 Nov 15;9(11):
Authors: Wieckiewicz M, Grychowska N, Zietek M, Wieckiewicz G, Smardz J
Tension-type headache (TTH) is the most common type of chronic recurring head pain. It can occur twice as often in women as in men. It is the most common type of headache. Its lifetime prevalence is 30% to 78% in the general population. TTH treatment should be multilevel. It often consists of taking pain medication, muscle relaxants, antidepressants, using biofeedback therapy, acupuncture, and attending behavioral therapy. Several clinical trials also suggest that botulinum toxin (BTX) may be an effective treatment option for such patients. The aim of this study was to evaluate if BTX can be used as a treatment method in TTH in the light of current medical literature. The authors searched the PubMed, EBSCOhost, OVID, Web of Knowledge, Cochrane Library and CINAHL databases to identify relevant publications. The authors finally included 11 papers-prospective and retrospective cohort studies. Among most of the selected studies, there was a significant correlation between using BTX and reduction of TTH pain intensity and severity. By analyzing qualified studies, it can be concluded that botulinum toxin seems to be effective in TTH management.
PMID: 29140286 [PubMed - in process]
Factors associated with home hazards: Findings from the Malaysian Elders Longitudinal Research study.
Geriatr Gerontol Int. 2017 Nov 15;:
Authors: Romli MH, Tan MP, Mackenzie L, Lovarini M, Kamaruzzaman SB, Clemson L
AIM: Previous studies have investigated home hazards as a risk factor for falls without considering factors associated with the presence of home hazards. The present study aimed to determine patterns of home hazards among urban community-dwelling older Malaysians, and to identify factors contributing to home hazards.
METHODS: Cross-sectional data from the initial wave of the Malaysian Elders Longitudinal Research study were used. Basic demographics were obtained from the Global Questionnaire. Basic and instrumental activities of daily living were measured using the Katz and Lawton-Brody scales, and home hazards were identified using the Home Falls and Accidents Screening Tool. Participants were also asked if they had fallen in the previous 12 months.
RESULTS: Data were analyzed from 1489 participants. Hazards were frequently identified (>30%) in the toilet and bathroom areas (no grab rail, no non-slip mat, distant toilet), slippery floors, no bedside light access and inappropriate footwear. Lower educational attainment, traditional housing, Chinese ethnicity, greater number of home occupants, lower monthly expenditure, poor vision and younger age were the factors independently associated with home hazards.
CONCLUSIONS: This study provides evidence that home hazards are a product of the interaction of the individual's function within their home environment. Hazards are also influenced by local sociocultural and environmental factors. The relationship between home hazards and falls appears complex and deserves further evaluation. Geriatr Gerontol Int 2017; ••: ••-••.
PMID: 29139186 [PubMed - as supplied by publisher]
Effect of light polarization on the efficiency of photodynamic therapy of basal cell carcinomas: an in vitro cellular study.
Lasers Med Sci. 2017 Nov 15;:
Authors: JalalKamali M, Nematollahi-Mahani SN, Shojaei M, Shamsoddini A, Arabpour N
In an in vitro study, the effect of light polarization on the efficiency of 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) of basal cell carcinoma (BCC) was investigated. Three states of light polarization (non-polarized, linearly polarized, and circularly polarized) were considered. Cells were exposed to green (532 pm 20 nm) irradiation from light emitting diodes. Cell survival was measured by the colorimetric assay (WST-1) and Trypan blue staining. The colorimetric assay showed a pronounced decrease in the cell viability (up to 30%) using polarized light compared to the non-polarized one in the wavelength region used. Similar results were obtained by the cell counting method (20-30% increase in cell death). The observed effect was dependent on the concentration of photosensitizer. The effect is more expressed in the case of linearly polarized light compared to the circularly polarized one. Results show that the use of polarized light increases the efficiency of in vitro ALA-PDT of BCC. Utilizing polarized light, it is possible to obtain the same effect from PDT by lower concentrations of photosensitizer. Additionally, the concentration dependency of PDT response and photo-bleaching is also reduced.
PMID: 29139000 [PubMed - as supplied by publisher]
Effects of cognitive load on the amount and temporal structure of postural sway variability in stroke survivors.
Exp Brain Res. 2017 Nov 14;:
Authors: Mehdizadeh H, Khalaf K, Ghomashchi H, Taghizadeh G, Ebrahimi I, Taghavi Azar Sharabiani P, Mousavi SJ, Parnianpour M
This study aimed to investigate the variability in postural sway patterns during quiet standing in stroke survivors. The postural sway was measured in 19 stroke survivors, as well as 19 healthy demographically matched participants, at 3 levels of postural difficulty (rigid surface with closed and open eyes, and foam surface with closed eyes), and 3 levels of cognitive difficulty (without a cognitive task, easy and difficult cognitive tasks). Both linear analyses (the amount of postural sway variability, including the standard deviation of the COP velocity in both the anteroposterior (AP) and mediolateral (ML) directions), as well as non-linear analyses [the temporal structure of the COP variability, including % Recurrence, % Determinism, Shannon Entropy, Trend and the maximum diagonal line (D max)] were employed. The results revealed that the amount of variability of the postural sway of stroke survivors was significantly greater than that of healthy participants, along both the ML and AP directions, with the highest obtained during standing on foam with closed eyes. All measures of the temporal structure of the COP variability were significantly greater in stroke survivors, as compared to the control group, along the ML direction, but not along the AP direction. The cognitive error was significantly higher during difficult cognitive tasks, although it was neither affected by postural difficulty nor by group. The different results obtained for the amount and temporal structure of the COP variability in the AP and ML directions shed light on the intricate mechanisms employed by the CNS in post-stroke balance control, and suggest that effective rehabilitative and therapeutic strategies should be patient-specific, taking both the environment/surface as well as the specific protocols into consideration.
PMID: 29138873 [PubMed - as supplied by publisher]
Prevention and treatment of acute and chronic radiodermatitis.
Breast Cancer (Dove Med Press). 2017;9:551-557
Authors: Seité S, Bensadoun RJ, Mazer JM
More than half the number of patients with cancer, who are treated with radiotherapy, will have radiodermatitis at some point during their treatment. Radiodermatitis either occurs early on in the treatment period or appears months or up to several years later. Acute radiodermatitis is a burn injury that varies in severity according to both treatment and inherent patient factors. Most acute radiodermatitis reactions resolve after several weeks but some reactions persist and can cause complications. Late-onset radiodermatitis is characterized by telangiectasia that forms on atrophic and fragile skin. These radiodermatitis reactions can have a significant negative impact on concomitant and subsequent therapeutic protocols and most particularly on the patient's quality of life. Today, treatment of radiodermatitis reactions is in its infancy. Although there is insufficient evidence available to form recommendations that would prevent or reduce radiodermatitis, some advances have been made using low level light therapy (LLLT) or vascular lasers to control the symptoms. Some recent preclinical and clinical research suggests that LLLT has biostimulating properties which allow the tissues to regenerate and heal faster, reduce inflammation, and prevent fibrosis. Also, in late-onset radiodermatitis pulsed dye laser treatment has been shown to be beneficial in clearing radiation-induced telangiectasia. In the absence of evidence-based recommendations, the objective of this paper is to review how to prevent or manage the symptoms of radiodermatitis reactions.
PMID: 29138594 [PubMed]
Photoactivatable RNAi for cancer gene therapy triggered by near-infrared-irradiated single-walled carbon nanotubes.
Int J Nanomedicine. 2017;12:7885-7896
Authors: Ren X, Lin J, Wang X, Liu X, Meng E, Zhang R, Sang Y, Zhang Z
The efficacy of RNA interference (RNAi)-based cancer gene therapy is limited by its unexpected side effects, thus necessitating a strategy to precisely trigger conditional gene knockdown. In this study, we engineered a novel photoactivatable RNAi system, named as polyetherimide-modified single-wall carbon nanotube (PEI-SWNT)/pHSP-shT, that enables optogenetic control of targeted gene suppression in tumor cells. PEI-SWNT/pHSP-shT comprises a stimulus-responsive nanocarrier (PEI-SWNT), and an Hsp70B'-promoter-driven RNAi vector (pHSP-shT). In response to near-infrared (NIR) light irradiation, heating of PEI-SWNT in breast MCF-7 cells triggered gene knockdown targeting human telomerase reverse transcriptase through RNAi, with the gene-knockdown activity capable of being switched off by extinguishing the NIR. Furthermore, we demonstrated that the photoactivatable RNAi system exhibited higher antitumor activity by combining gene therapy and photothermal therapy, both in vitro and in vivo. Optogenetic control of RNAi based on an NIR-activated nanocarrier will potentially facilitate improved understanding of molecular-targeted gene therapy in human malignant tumors.
PMID: 29138556 [PubMed - in process]
FOXO1/3: Potential suppressors of fibrosis.
Ageing Res Rev. 2017 Nov 11;41:42-52
Authors: Xin Z, Ma Z, Hu W, Jiang S, Yang Z, Li T, Chen F, Jia G, Yang Y
Fibrosis is a universally age-related disease that involves nearly all organs. It is typically initiated by organic injury and eventually results in organ failure. There are still few effective therapeutic strategy targets for fibrogenesis. Forkhead box proteins O1 and O3 (FOXO1/3) have been shown to have favorable inhibitory effects on fibroblast activation and subsequent extracellular matrix production and can ameliorate fibrosis levels in numerous organs, including the heart, liver, lung, and kidney; they are therefore promising targets for anti-fibrosis therapy. Moreover, we can develop appropriate strategies to make the best use of FOXO1/3's anti-fibrosis properties. The information reviewed here should be significant for understanding the roles of FOXO1/3 in fibrosis and should contribute to the design of further studies related to FOXO1/3 and the fibrotic response and shed light on a potential treatment for fibrosis.
PMID: 29138094 [PubMed - as supplied by publisher]
Heightened TWEAK-NF-κB signaling and inflammation-associated fibrosis in paralyzed muscles of men with chronic spinal cord injury.
Am J Physiol Endocrinol Metab. 2016 May 01;310(9):E754-61
Authors: Yarar-Fisher C, Bickel CS, Kelly NA, Stec MJ, Windham ST, McLain AB, Oster RA, Bamman MM
Individuals with long-standing spinal cord injury (SCI) often present with extreme muscle atrophy and impaired glucose metabolism at both the skeletal muscle and whole body level. Persistent inflammation and increased levels of proinflammatory cytokines in the skeletal muscle are potential contributors to dysregulation of glucose metabolism and atrophy; however, to date no study has assessed the effects of long-standing SCI on their expression or intracellular signaling in the paralyzed muscle. In the present study, we assessed the expression of genes (TNFαR, TNFα, IL-6R, IL-6, TWEAK, TWEAK R, atrogin-1, and MuRF1) and abundance of intracellular signaling proteins (TWEAK, TWEAK R, NF-κB, and p-p65/p-50/105) that are known to mediate inflammation and atrophy in skeletal muscle. In addition, based on the effects of muscle inflammation on promotion of skeletal muscle fibrosis, we assessed the degree of fibrosis between myofibers and fascicles in both groups. For further insight into the distribution and variability of muscle fiber size, we also analyzed the frequency distribution of SCI fiber size. Resting vastus lateralis (VL) muscle biopsy samples were taken from 11 men with long-standing SCI (≈22 yr) and compared with VL samples from 11 able-bodied men of similar age. Our results demonstrated that chronic SCI muscle has heightened TNFαR and TWEAK R gene expression and NF-κB signaling (higher TWEAK R and phospho-NF-κB p65) and fibrosis, along with substantial myofiber size heterogeneity, compared with able-bodied individuals. Our data suggest that the TWEAK/TWEAK R/NF-κB signaling pathway may be an important mediator of chronic inflammation and fibrotic adaptation in SCI muscle.
PMID: 26931128 [PubMed - indexed for MEDLINE]
Secukinumab: Benefit Assessment According to §35a Social Code Book V
Book. 2015 08 28Authors: Institute for Quality and Efficiency in Health Care
In accordance with §35a Social Code Book (SGB) V, the Federal Joint Committee (G-BA) commissioned the Institute for Quality and Efficiency in Health Care (IQWiG) to assess the benefit of the drug secukinumab. The assessment was based on a dossier compiled by the pharmaceutical company (hereinafter referred to as “the company”). The dossier was sent to IQWiG on 1 June 2015. Research question
The aim of this report was to assess the added benefit of secukinumab in comparison with the appropriate comparator therapy (ACT) in patients with moderate to severe plaque psoriasis who are candidates for systemic therapy. The G-BA specified individually optimized standard treatment under consideration of fumaric acid esters or cyclosporine or methotrexate or phototherapy as ACT for research question A. Deviating from the G-BA, the company chose methotrexate as only comparator therapy. For research question B, the company followed the G-BA’s specification and chose ustekinumab as only ACT. The present assessment was conducted in comparison with the G-BA’s ACT. The assessment was conducted based on patient-relevant outcomes and on the evidence provided by the company in the dossier. Randomized controlled trials (RCTs) with a minimum duration of 24 weeks were to be included in the assessment.