Cybermedlife - Therapeutic Actions Blood Donation

Effects of phlebotomy-induced reduction of body iron stores on metabolic syndrome: results from a randomized clinical trial.

Abstract Title: Effects of phlebotomy-induced reduction of body iron stores on metabolic syndrome: results from a randomized clinical trial. Abstract Source: BMC Med. 2012 ;10:54. Epub 2012 May 30. PMID: 22647517 Abstract Author(s): Khosrow S Houschyar, Rainer Lüdtke, Gustav J Dobos, Ulrich Kalus, Martina Broecker-Preuss, Thomas Rampp, Benno Brinkhaus, Andreas Michalsen Article Affiliation: Department of Internal Medicine, Kliniken Essen-Mitte, University Duisburg-Essen, Essen, Germany. Abstract: BACKGROUND: Metabolic syndrome (METS) is an increasingly prevalent but poorly understood clinical condition characterized by insulin resistance, glucose intolerance, dyslipidemia, hypertension, and obesity. Increased oxidative stress catalyzed by accumulation of iron in excess of physiologic requirements has been implicated in the pathogenesis of METS, but the relationships between cause and effect remain uncertain. We tested the hypothesis that phlebotomy-induced reduction of body iron stores would alter the clinical presentation of METS, using a randomized trial. METHODS: In a randomized, controlled, single-blind clinical trial, 64 patients with METS were randomly assigned to iron reduction by phlebotomy (n = 33) or to a control group (n = 31), which was offered phlebotomy at the end of the study (waiting-list design). The iron-reduction patients had 300 ml of blood removed at entry and between 250 and 500 ml removed after 4 weeks, depending on ferritin levels at study entry. Primary outcomes were change in systolic blood pressure (SBP) and insulin sensitivity as measured by Homeostatic Model Assessment (HOMA) index after 6 weeks. Secondary outcomes included HbA1c, plasma glucose, blood lipids, and heart rate (HR). RESULTS: SBP decreased from 148.5± 12.3 mmHg to 130.5 ± 11.8 mmHg in the phlebotomy group, and from 144.7 ± 14.4 mmHg to 143.8 ± 11.9 mmHg in the control group (difference -16.6 mmHg; 95% CI -20.7 to -12.5; P<0.001). No significant effect on HOMA index was seen. With regard to secondary outcomes, blood glucose, HbA1c, low-density lipoprotein/high-density lipoprotein ratio, and HR were significantly decreased by phlebotomy. Changes in BP and HOMA index correlated with ferritin reduction. CONCLUSIONS: In patients with METS, phlebotomy, with consecutive reduction of body iron stores, lowered BP and resulted in improvements in markers of cardiovascular risk and glycemic control. Blood donation may have beneficial effects for blood donors with METS. TRIAL REGISTRATION: NCT01328210 Please see related article: Article Published Date : Dec 31, 2011
Therapeutic Actions Blood Donation

NCBI pubmed

Microfluidic whole blood testing of platelet response to pharmacological agents.

Related Articles Microfluidic whole blood testing of platelet response to pharmacological agents. Platelets. 2017 Jan 19;:1-6 Authors: Li R, Grosser T, Diamond SL Abstract Platelets present a number of intracellular and transmembrane targets subject to pharmacological modulation, either for cardiovascular disease reduction or as an unintended drug response. Microfluidic devices allow human blood to clot on a defined surface under controlled hemodynamic and pharmacological conditions. The potencies of a number of antiplatelet and anticancer drugs have been tested with respect to platelet deposition on collagen under flow. Inhibitors of cyclooxygenase-1 (COX-1) reduce platelet deposition, either when added ex vivo to blood or ingested orally by patients prior to testing. Some individuals display a functional "aspirin-insensitivity" in microfluidic assay. When certain nonsteroidal anti-inflammatory drugs (NSAIDs) are taken orally, they block COX-1 acetylation by aspirin with concomitant reduction of aspirin efficacy against platelets in microfluidic assay. Both P2Y1 and P2Y12 inhibitors reduce platelet deposition under flow, as do NO donors and iloprost that target the guanylate cyclase and the prostacyclin receptor, respectively. In a microfluidic assay of 37 kinase inhibitors, dasatinib had potent antiplatelet activity, while bosutinib was less potent. Dasatinib and bosutinib have known profiles against numerous kinases, revealing overlapping and nonoverlapping activities relevant to their unique actions against platelets. Also, dasatinib caused a marked and specific inhibition of GPVI signaling induced by convulxin, consistent with a dasatinib-associated bleeding risk. Microfluidic devices facilitate drug library screening, dose-response testing, and drug-drug interaction studies. Kinase inhibitors developed as anticancer agents may present antiplatelet activities that are detectable by microfluidic assay and potentially linked to bleeding risks. PMID: 28102731 [PubMed - as supplied by publisher]

CD14(++) CD16(-) monocytes are the main source of 11β-HSD type 1 after IL-4 stimulation.

Related Articles CD14(++) CD16(-) monocytes are the main source of 11β-HSD type 1 after IL-4 stimulation. Int Immunopharmacol. 2017 Feb;43:156-163 Authors: Kunnathully V, Gomez-Lira M, Bassi G, Poli F, Zoratti E, La Verde V, Idolazzi L, Gatti D, Viapiana O, Adami S, Rossini M Abstract The anti-inflammatory actions of IL-4 are well established through earlier findings. However, the exact mechanism it uses to downregulate the pro-inflammatory cytokine production through monocytes and macrophages is poorly understood. In this study, we examined the effect of IL-4 in the induction of 11β-HSD1 in the two main classes of monocytes, CD14(++) CD16(-) (CD14) and CD14(+) CD16(+) (CD16). Peripheral Blood Mononuclear Cells (PBMCs) were isolated from 17 healthy donors and were sorted into CD14 and CD16 subpopulations using cell sorting. Effect of IL-4 on 11β-HSD1-enzyme activity was measured in sorted and unsorted monocytes using Homogeneous Time-Resolved Fluorescence (HTRF) and M1/M2 polarization analysis was performed by flow cytometry. Our results indicate that CD14 cells are the major source of 11β-HSD1 enzyme after IL-4 stimulation and that M2 phenotype is not a pre-requisite for its synthesis. PMID: 27998829 [PubMed - indexed for MEDLINE]

S-Nitrosothiols as Platforms for Topical Nitric Oxide Delivery.

Related Articles S-Nitrosothiols as Platforms for Topical Nitric Oxide Delivery. Basic Clin Pharmacol Toxicol. 2016 Oct;119 Suppl 3:49-56 Authors: Ganzarolli de Oliveira M Abstract Nitric oxide (NO) is a small radical species involved in several fundamental physiological processes, including the control of vascular tone, the immune response and neuronal signalling. Endothelial dysfunction with the decreased NO bioavailability is the underlying cause of several diseases and has led to the development of a wide range of systemic NO donor compounds to lower the blood pressure and control hypertensive crises. However, several potential therapeutic actions of NO, not related to the cardiovascular system, demand exclusively local actions. Primary S-nitrosothiols (RSNOs) are endogenously found NO carriers and donors and have emerged as platforms for the localized delivery of NO in topical applications. Formulations for this purpose have evolved from low molecular weight RSNOs incorporated in polymeric films, hydrogels and viscous vehicles, to polymeric RSNOs where the SNO moiety is covalently bound to the polymer backbone. The biological actions displayed by these formulations include the increase in dermal vasodilation, the acceleration of wound healing, the killing of infectious microorganisms and an analgesic action against inflammatory pain. This MiniReview focuses on the state of the art of experimental topical formulations for NO delivery based on S-nitrosothiols and their potential therapeutic applications. PMID: 27030007 [PubMed - indexed for MEDLINE]

Intravenous immune globulin suppresses angiogenesis in mice and humans.

Related Articles Intravenous immune globulin suppresses angiogenesis in mice and humans. Signal Transduct Target Ther. 2016;1: Authors: Yasuma R, Cicatiello V, Mizutani T, Tudisco L, Kim Y, Tarallo V, Bogdanovich S, Hirano Y, Kerur N, Li S, Yasuma T, Fowler BJ, Wright CB, Apicella I, Greco A, Brunetti A, Ambati BK, Helmers SB, Lundberg IE, Viklicky O, Leusen JH, Verbeek JS, Gelfand BD, Bastos-Carvalho A, De Falco S, Ambati J Abstract Human intravenous immune globulin (IVIg), a purified IgG fraction composed of ~ 60% IgG1 and obtained from the pooled plasma of thousands of donors, is clinically used for a wide range of diseases. The biological actions of IVIg are incompletely understood and have been attributed both to the polyclonal antibodies therein and also to their IgG (IgG) Fc regions. Recently, we demonstrated that multiple therapeutic human IgG1 antibodies suppress angiogenesis in a target-independent manner via FcγRI, a high-affinity receptor for IgG1. Here we show that IVIg possesses similar anti-angiogenic activity and inhibited blood vessel growth in five different mouse models of prevalent human diseases, namely, neovascular age-related macular degeneration, corneal neovascularization, colorectal cancer, fibrosarcoma and peripheral arterial ischemic disease. Angioinhibition was mediated by the Fc region of IVIg, required FcγRI and had similar potency in transgenic mice expressing human FcγRs. Finally, IVIg therapy administered to humans for the treatment of inflammatory or autoimmune diseases reduced kidney and muscle blood vessel densities. These data place IVIg, an agent approved by the US Food and Drug Administration, as a novel angioinhibitory drug in doses that are currently administered in the clinical setting. In addition, they raise the possibility of an unintended effect of IVIg on blood vessels. PMID: 26925256 [PubMed - as supplied by publisher]

A novel dual NO-donating oxime and c-Jun N-terminal kinase inhibitor protects against cerebral ischemia-reperfusion injury in mice.

Related Articles A novel dual NO-donating oxime and c-Jun N-terminal kinase inhibitor protects against cerebral ischemia-reperfusion injury in mice. Neurosci Lett. 2016 Apr 08;618:45-9 Authors: Atochin DN, Schepetkin IA, Khlebnikov AI, Seledtsov VI, Swanson H, Quinn MT, Huang PL Abstract The c-Jun N-terminal kinase (JNK) has been shown to be an important regulator of neuronal cell death. Previously, we synthesized the sodium salt of 11H-indeno[1,2-b]quinoxalin-11-one (IQ-1S) and demonstrated that it was a high-affinity inhibitor of the JNK family. In the present work, we found that IQ-1S could release nitric oxide (NO) during its enzymatic metabolism by liver microsomes. Moreover, serum nitrite/nitrate concentration in mice increased after intraperitoneal injection of IQ-1S. Because of these dual actions as JNK inhibitor and NO-donor, the therapeutic potential of IQ-1S was evaluated in an animal stroke model. We subjected wild-type C57BL6 mice to focal ischemia (30min) with subsequent reperfusion (48h). Mice were treated with IQ-1S (25mg/kg) suspended in 10% solutol or with vehicle alone 30min before and 24h after middle cerebral artery (MCA) occlusion (MCAO). Using laser-Doppler flowmetry, we monitored cerebral blood flow (CBF) above the MCA during 30min of MCAO provoked by a filament and during the first 30min of subsequent reperfusion. In mice treated with IQ-1S, ischemic and reperfusion values of CBF were not different from vehicle-treated mice. However, IQ-1S treated mice demonstrated markedly reduced neurological deficit and infarct volumes as compared with vehicle-treated mice after 48h of reperfusion. Our results indicate that the novel JNK inhibitor releases NO during its oxidoreductive bioconversion and improves stroke outcome in a mouse model of cerebral reperfusion. We conclude that IQ-1S is a promising dual functional agent for the treatment of cerebral ischemia and reperfusion injury. PMID: 26923672 [PubMed - indexed for MEDLINE]

[An experience of hepatitis B control in a rural area in Far North Cameroon].

Related Articles [An experience of hepatitis B control in a rural area in Far North Cameroon]. Med Sante Trop. 2015 Oct-Dec;25(4):422-7 Authors: Loriette M, Birguel J, Damza R, Ratoua M, Karsikam S, Sobnangou JJ, Aurenche C, Lunel-Fabiani F, Huraux JM Abstract Experience of four years of control of the transmission of hepatitis B in a rural area in Far North Cameroon is presented: (i) prevention of mother to child transmission, (ii) HBsAg screening before blood transfusion, (iii) detection of HIV/HBV co-infections, (iv) protection of healthcare workers. The prevalence of HBsAg is very high in the four populations studied: 18.2% of pregnant women, 16.9% of candidate for blood donation, 14.4% of people living with HIV and 18 % of healthcare workers. Despite limited resources, effective actions are possible. Prevention of mother to child transmission of HBV with vaccination at birth has been set up, with bottlenecks - similar to those observed in HIV - but decreasing over the study. The screening of all potential blood donors has been reached over the years for HIV, HBsAg and HCV, which has led to the eviction of one out of five potential blood donors. Screening of healthcare workers reminded us that adult protection is based on a very early vaccination and not when hiring, even if it is possible to diagnose rare adults eligible for vaccination by research of anti-HBc antibody. A program of hepatitis B control, essential in Africa, appears feasible in rural areas in a framework of an overall improvement in care delivery. PMID: 26643767 [PubMed - indexed for MEDLINE]

Novel vitamin D analogues; cytotoxic and anti-proliferative activity against a diffuse large B-cell lymphoma cell line and B-cells from healthy donors.

Related Articles Novel vitamin D analogues; cytotoxic and anti-proliferative activity against a diffuse large B-cell lymphoma cell line and B-cells from healthy donors. J Steroid Biochem Mol Biol. 2016 Nov;164:98-105 Authors: Kozielewicz P, Grafton G, Kutner A, Curnow SJ, Gordon J, Barnes NM Abstract Calcitriol (1,25-dihydroxyvitamin D3, 1,25D3) and vitamin D side-chain modified analogs (VDAs) have gained considerable attention as potential drugs in the treatment of acute myeloid leukemia (AML), yet studies of the impact of 1,25D3 and VDAs upon other haematological malignancies are more limited. To address this gap in knowledge, we have examined the action of 1,25D3 and VDAs on a human cell line (DOHH2, K422) typifying diffuse large B-cell lymphoma (DLBCL) and also peripheral blood B-cells isolated from healthy donors. 1,25D3 and certain VDAs displayed moderate cytotoxic and pro-apoptotic actions upon DLBCL cells. 1,25D3 and VDAs (100nM) caused the death of approximately 40% DOHH2 cells after 24h stimulation, similar to their impact on HL-60 cells (acute myeloid leukaemia cell line). In addition, 1,25D3 and VDAs displayed concentration and time-dependent anti-proliferative actions upon stimulated B-cells from healthy donors. The VDAs inhibited proliferation by approximately 30%. Hence VDAs may offer therapeutic potential for the treatment of DLBCL or conditions benefitted by B-cell depletion. PMID: 26485664 [PubMed - in process]

In Vivo Effects of Mesenchymal Stromal Cells in Two Patients With Severe Acute Respiratory Distress Syndrome.

Related Articles In Vivo Effects of Mesenchymal Stromal Cells in Two Patients With Severe Acute Respiratory Distress Syndrome. Stem Cells Transl Med. 2015 Oct;4(10):1199-213 Authors: Simonson OE, Mougiakakos D, Heldring N, Bassi G, Johansson HJ, Dalén M, Jitschin R, Rodin S, Corbascio M, El Andaloussi S, Wiklander OP, Nordin JZ, Skog J, Romain C, Koestler T, Hellgren-Johansson L, Schiller P, Joachimsson PO, Hägglund H, Mattsson M, Lehtiö J, Faridani OR, Sandberg R, Korsgren O, Krampera M, Weiss DJ, Grinnemo KH, Le Blanc K Abstract UNLABELLED: Mesenchymal stromal cells (MSCs) have been investigated as a treatment for various inflammatory diseases because of their immunomodulatory and reparative properties. However, many basic questions concerning their mechanisms of action after systemic infusion remain unanswered. We performed a detailed analysis of the immunomodulatory properties and proteomic profile of MSCs systemically administered to two patients with severe refractory acute respiratory distress syndrome (ARDS) on a compassionate use basis and attempted to correlate these with in vivo anti-inflammatory actions. Both patients received 2×10(6) cells per kilogram, and each subsequently improved with resolution of respiratory, hemodynamic, and multiorgan failure. In parallel, a decrease was seen in multiple pulmonary and systemic markers of inflammation, including epithelial apoptosis, alveolar-capillary fluid leakage, and proinflammatory cytokines, microRNAs, and chemokines. In vitro studies of the MSCs demonstrated a broad anti-inflammatory capacity, including suppression of T-cell responses and induction of regulatory phenotypes in T cells, monocytes, and neutrophils. Some of these in vitro potency assessments correlated with, and were relevant to, the observed in vivo actions. These experiences highlight both the mechanistic information that can be gained from clinical experience and the value of correlating in vitro potency assessments with clinical effects. The findings also suggest, but do not prove, a beneficial effect of lung protective strategies using adoptively transferred MSCs in ARDS. Appropriate randomized clinical trials are required to further assess any potential clinical efficacy and investigate the effects on in vivo inflammation. SIGNIFICANCE: This article describes the cases of two patients with severe refractory adult respiratory syndrome (ARDS) who failed to improve after both standard life support measures, including mechanical ventilation, and additional measures, including extracorporeal ventilation (i.e., in a heart-lung machine). Unlike acute forms of ARDS (such in the current NIH-sponsored study of mesenchymal stromal cells in ARDS), recovery does not generally occur in such patients. PMID: 26285659 [PubMed - indexed for MEDLINE]

The role of uncertainty regarding the results of screening immunoassays in blood establishments.

Related Articles The role of uncertainty regarding the results of screening immunoassays in blood establishments. Transfus Apher Sci. 2015 Apr;52(2):252-5 Authors: Pereira P, Westgard JO, Encarnação P, Seghatchian J, de Sousa G Abstract The risk of uncertain results in infectious agents' tests is recognized in blood establishments, being particularly evident during the blood donor selection. The current risk-based approaches require risk assessment and "risk-based thinking". Accordingly, the blood establishment should consider the effect of uncertainty in all the technical decisions taken in a screening laboratory. Since the post-transfusion safety is one of the blood establishments' goals, the risk of post-transfusion infection should be evaluated and actions taken to decrease the chance of blood donations validation use false negative results. This article reviews and discusses the sources of uncertainty of infectious agents' reported results in blood establishments. It describes a set of sources of uncertainty that should be considered in screening immunoassay's decisions. The infectious agents' uncertainty concern is critical for reporting reliable results. PMID: 25754470 [PubMed - indexed for MEDLINE]

[Organization for the coverage of the transfusional needs of patients with hemoglobinopathy at the Établissement français du sang Bretagne].

Related Articles [Organization for the coverage of the transfusional needs of patients with hemoglobinopathy at the Établissement français du sang Bretagne]. Transfus Clin Biol. 2015 Mar;22(1):5-11 Authors: Thibert JB, Danic B, Delamaire M, Delugin L, Dugor C, Le Vacon F, Nimubona S, Treussard D, Vasse J, Semana G Abstract UNLABELLED: Brittany is a low prevalence region for hemoglobinopathies. Despite of that, the number of patients is increasing each year. In 2013, 140 patients were known at the EFS Bretagne, and medical consultations are growing for 50% each year since 2011. The consequence is an increase of needs of 22% of compatible packed red blood cells. To anticipate the announced progress, various actions were implemented as study groups, creation of a new informatic prescription for red blood cells phenotyping, promotion of donation, transfusion organisation. RESULTS: Fifthty-nine percent of the 400 ABO RH-KELL, FY, JK, MNS 3, 4, red blood cells were realised on the basis of this new informatic prescription, as the 99% of the packed red blood cells identified Fy (a- b-). So, 92% of the compatible transfused packed red blood cells were already in stock when the patients needed them. CONCLUSIONS: In Brittany, that organisation leads to assume qualitative and quantitative transfusion for sickle cell disease in more than 90% of cases, with fast distribution. In the same time promotion of donation is done to increase the diversity of donors. PMID: 25441455 [PubMed - indexed for MEDLINE]

Postdonation information and blood component retrievals: realigning blood center and hospital actions based on risk assessment.

Related Articles Postdonation information and blood component retrievals: realigning blood center and hospital actions based on risk assessment. Transfus Med Rev. 2014 Oct;28(4):226-34 Authors: Eder AF, Goldman M Abstract Blood centers often receive information from individuals after blood donation that should have resulted in their deferral and may attempt to retrieve distributed blood components that did not meet all quality standards and regulations. Typically, the information is discovered or reported only after the components from the donation have been transfused. Blood centers may notify the transfusion service and provide a statement of the potential risk, if any, associated with the blood components, but the transfusion service must decide if further investigation, notification of the transfusing physician, or counseling of the patient is warranted. Currently, postdonation information (PDI) affects an estimated 1 in 600 donations in the United States. Despite the regularity with which PDI occurs, there has been little analysis of the main sources of PDI, associated transfusion risk, or the actual benefit of various actions taken as a result of PDI. However, blood centers attempt to retrieve thousands of components each year for PDI: actions that can cause confusion, concern, and complaints from hospitals and transfusion services. Postdonation information is largely a reflection of the inherent limitations of the current donor screening process, which is error-prone and uses broad, precautionary questions to guard against theoretical or extremely remote risks. This article reviews the most commonly reported PDI and available information on the possible risk associated with the transfused components from the involved donations, to formulate a framework for blood center retrieval actions and hospital notification that is consistent with current regulations and commensurate with the likelihood of adverse outcomes associated with the most commonly reported PDI. PMID: 25311469 [PubMed - indexed for MEDLINE]

Recent developments in the effects of nitric oxide-donating statins on cardiovascular disease through regulation of tetrahydrobiopterin and nitric oxide.

Related Articles Recent developments in the effects of nitric oxide-donating statins on cardiovascular disease through regulation of tetrahydrobiopterin and nitric oxide. Vascul Pharmacol. 2014 Nov;63(2):63-70 Authors: Ma S, Ma CC Abstract Since the discovery of the importance of nitric oxide (NO) to the human body three decades ago, numerous laboratory and clinical studies have been done to explore its potential therapeutic actions on many organs. In the cardiovascular system, NO works as a volatile signaling molecule regulating the vascular permeability and vascular tone, preventing thrombosis and inflammation, as well as inhibiting the smooth muscle hyperplasia. Thus, NO is important in the prevention and treatment of cardiovascular disease. NO is synthesized by NO synthase (NOS) with tetrahydrobiopterin (BH4) as the crucial cofactor. Many studies have been done to form nitric oxide donors so as to deliver NO directly to the vessel walls. In addition, NO moieties have been incorporated into existing therapeutic agents to enhance the NO bioavailability, including statins. Statins are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA), the rate-limiting enzyme of the mevalonate pathway. By inhibiting this pathway, statins lower blood cholesterol and exert their pleiotropic effects through activity in reaction cascades, such as Rho/ROCK and Rac 1/NADPH oxidase pathways. Statins have also been observed to implement their non-lipid effects by promoting BH4 synthesis with increase of NO bioavailability. Furthermore, NO-donating statins in laboratory studies have demonstrated to produce better therapeutic effects than their parent's drugs. They offer better anti-inflammatory, anti-proliferative and antithrombotic actions on cardiovascular system. They also cause better revascularization in peripheral ischemia and produce greater enhancement in limb reperfusion and salvage. In addition, it has been shown that NO-donating statin caused less myotoxicity, the most common side effect related to treatment with statins. The initial studies have demonstrated the superior therapeutic effects of NO-donating statins while producing fewer side effects. PMID: 25139660 [PubMed - indexed for MEDLINE]

[Improving blood safety: errors management in transfusion medicine].

Related Articles [Improving blood safety: errors management in transfusion medicine]. Srp Arh Celok Lek. 2014 May-Jun;142(5-6):384-90 Authors: Bujandrić N, Grujić J, Krga-Milanović M Abstract INTRODUCTION: The concept of blood safety includes the entire transfusion chain starting with the collection of blood from the blood donor, and ending with blood transfusion to the patient. The concept involves quality management system as the systematic monitoring of adverse reactions and incidents regarding the blood donor or patient. Monitoring of near-miss errors show the critical points in the working process and increase transfusion safety. OBJECTIVE: The aim of the study was to present the analysis results of adverse and unexpected events in transfusion practice with a potential risk to the health of blood donors and patients. METHODS: One-year retrospective study was based on the collection, analysis and interpretation of written reports on medical errors in the Blood Transfusion Institute of Vojvodina. RESULTS: Errors were distributed according to the type, frequency and part of the working process where they occurred. Possible causes and corrective actions were described for each error. The study showed that there were not errors with potential health consequences for the blood donor/patient. Errors with potentially damaging consequences for patients were detected throughout the entire transfusion chain. Most of the errors were identified in the preanalytical phase. The human factor was responsible for the largest number of errors. CONCLUSION: Error reporting system has an important role in the error management and the reduction of transfusion-related risk of adverse events and incidents. The ongoing analysis reveals the strengths and weaknesses of the entire process and indicates the necessary changes. Errors in transfusion medicine can be avoided in a large percentage and prevention is cost-effective, systematic and applicable. PMID: 25033600 [PubMed - indexed for MEDLINE]

Pharmacological strategy designed to limit ischemia-reperfusion injury in brain dead donor kidneys.

Related Articles Pharmacological strategy designed to limit ischemia-reperfusion injury in brain dead donor kidneys. Prog Urol. 2014 Jun;24 Suppl 1:S26-30 Authors: Branchereau J, Barrou B Abstract Ischemia-reperfusion injury is a complex physiological process responsible for delayed renal function or primary graft non-function, explicitly when kidney allograft are issued from expanded criteria donor. The purpose of this review is to detail the detrimental phenomenons altering kidney allograft's integrity in brain dead donor, therefore suggesting pharmacological interventions aiming to reduce ischemia-reperfusion injuries and improving transplantation outcome. This ischemia-reperfusion phenomenon must therefore be anticipated through the whole procedure starting at the stage of conditioning of the potential donor. Hormonal and haemodynamic consequences of brain death modify perfusion and oxygenation conditions of the organs Thus, after describing the autonomic, metabolic, endocrine and chemokine storm occurring during brain death, the authors focus on strategies to prevent hemodynamic instability in the donor and to limit the consequences of hormonal and immunological changes on organs that will eventually be transplanted. PMID: 24950929 [PubMed - indexed for MEDLINE]

Prevalence and trend of major transfusion-transmissible infections among blood donors in Western China, 2005 through 2010.

Related Articles Prevalence and trend of major transfusion-transmissible infections among blood donors in Western China, 2005 through 2010. PLoS One. 2014;9(4):e94528 Authors: Song Y, Bian Y, Petzold M, Ung CO Abstract BACKGROUND: The prevalence of transfusion-transmissible infections (TTIs) in blood donations is important for evaluating blood safety and potential risks to the population. This study investigated the prevalence of TTIs among blood donors in Western China and suggested measures for policy-makers. METHODS: The screening results of 66,311 donations between 2005 and 2010 from a central blood center in Western China were analyzed. The prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and syphilis infections were expressed in percentages for the entire study group as well as groups by demographic characteristics and donation frequency, with differences analyzed using Fisher's exact or Chi-square test. Logistic regression was performed to identify the influencing factors of the detected results. RESULTS: 1,769 (2.67%, 95% CI 2.55-2.79%) of the donated blood had serological evidence of infection with at least one pathogen and 44 (0.07%, 95% CI 0.05-0.09%) showed evidence of multiple infections. The seroprevalence of HBV, HCV, HIV, and syphilis infections was 0.87% (95% CI 0.80-0.94%), 0.86% (95% CI 0.79-0.93%), 0.31% (95% CI 0.26-0.35%), and 0.70% (95% CI 0.64-0.76%) respectively. Trend analysis for the prevalence of TTIs showed a significant increase from 2.44% to 3.71% (χ2 = 100.72, p = 0.00) over this 6-year period. The positive rates for TTIs varied along demographic lines. The top three risk factors in test-positive donors were identified as age, education level and donation frequency. The older age group and lower educated group were linked to a higher prevalence of TTIs. A decreasing prevalence was associated with an increasing frequency of blood donations (χ2 = 562.78, p = 0.00). CONCLUSIONS: Hepatitis B and C were found most, and often in conjunction with syphilis. These were the primary threats to blood safety. The high positivity rate and the increasing prevalence of TTIs among blood donors in Western China call for further actions. PMID: 24714490 [PubMed - indexed for MEDLINE]

Gamma irradiation preserves immunosuppressive potential and inhibits clonogenic capacity of human bone marrow-derived mesenchymal stromal cells.

Related Articles Gamma irradiation preserves immunosuppressive potential and inhibits clonogenic capacity of human bone marrow-derived mesenchymal stromal cells. J Cell Mol Med. 2014 Jun;18(6):1184-93 Authors: de Andrade AV, Riewaldt J, Wehner R, Schmitz M, Odendahl M, Bornhäuser M, Tonn T Abstract Mesenchymal stromal cells (MSCs) are promising candidates for the treatment of graft-versus-host and autoimmune diseases. Here, by virtue of their immunosuppressive effects, they are discussed to exhibit inhibitory actions on various immune effector cells, including T lymphocytes that promote the underlying pathology. While it becomes apparent that MSCs exhibit their therapeutic effect in a transient manner, they are usually transplanted from third party donors into heavily immunocompromised patients. However, little is known about potential late complications of persisting third party MSCs in these patients. We therefore analysed the effect of gamma irradiation on the potency and proliferation of MSCs to elucidate an irradiation dose, which would allow inhibition of MSC proliferation while at the same time preserving their immunosuppressive function. Bone marrow-derived MSCs (BM-MSCs) were gamma-irradiated at increasing doses of 5, 10 and 30 Gy and subsequently assessed by colony formation unit (CFU)-assay, Annexin V-staining and in a mixed lymphocyte reaction, to assess colony growth, apoptosis and the immunosuppressive capacity, respectively. Complete loss of proliferative capacity measured by colony formation was observed after irradiation with a dose equal to or greater than 10 Gy. No significant decrease of viable cells was detected, as compared to non-irradiated BM-MSCs. Notably, irradiated BM-MSCs remained highly immunosuppressive in vitro for at least 5 days after irradiation. Gamma irradiation does not impair the immunosuppressive capacity of BM-MSCs in vitro and thus might increase the safety of MSC-based cell products in clinical applications. PMID: 24655362 [PubMed - indexed for MEDLINE]

Contributions of endothelial nitric oxide synthase, noradrenaline, and neuropeptide Y to local warming-induced cutaneous vasodilatation in men.

Related Articles Contributions of endothelial nitric oxide synthase, noradrenaline, and neuropeptide Y to local warming-induced cutaneous vasodilatation in men. Microvasc Res. 2013 Nov;90:128-34 Authors: Hodges GJ, Sparks PA Abstract We performed a two-part study to determine the roles of endothelial nitric oxide synthase (eNOS) and the vasoconstrictor nerves neurotransmitters noradrenaline (NA) and neuropeptide Y (NPY) in the cutaneous vasodilator response to local skin warming. Forearm skin sites were instrumented with intradermal microdialysis fibres, local heaters, and laser-Doppler flow (LDF) probes. Sites were locally heated from 34 to 42°C. LDF was expressed as cutaneous vascular conductance (CVC; LDF/mean arterial pressure). In Part I, we tested whether sympathetic noradrenergic nerves acted via eNOS. In 8 male participants, treatments were as follows: 1) untreated; 2) bretylium tosylate (BT), preventing sympathetic neurotransmitter release; 3) l-NAA to inhibit eNOS; and 4) combined BT+l-NAA. At treated sites, the initial peak response was markedly reduced, and the plateau phase response to 35min of local warming was also reduced (P<0.05), which was not different among those sites (P>0.05). In Part II, we tested whether NA and NPY were involved in the vasodilator response to local warming. In Part IIa, treatments were: 1) untreated; 2) propranolol and yohimbine to antagonize α- and β-receptors; 3) l-NAA; and 4) combined propranolol, yohimbine, and l-NAA. In Part IIb, conditions were: 1) untreated; 2) BIBP to antagonize Y1-receptors; 3) l-NAA; and 4) combined BIBP and l-NAA. All treatments caused a reduction in the initial peak and plateau responses to local skin warming (P<0.05). The results of Part II indicate that both NA and NPY play roles in the cutaneous vasodilator response and their actions are achieved via eNOS. These data indicate that NA and NPY are involved in the initial, rapid rise in skin blood flow at the onset of local skin warming. However, their vasodilator actions in response to local skin warming appears to be manifested through eNOS. PMID: 24012636 [PubMed - indexed for MEDLINE]

[Personalized medicine in transplantation therapy].

Related Articles [Personalized medicine in transplantation therapy]. Rinsho Byori. 2013 May;61(5):428-33 Authors: Nakatani K Abstract Personalized medicine based on pharmacogenomics is being developed at the clinical stage. Various evidence is accumulating in transplantation therapy. Tacrolimus, a calcineurin inhibitor, is usually used for immunosuppressive therapy after transplantation. Tacrolimus is mainly metabolized by cytochrome P450 isozymes, CYP3A4 and CYP3A5, expressed in the intestine as well as in the liver. Recent studies of pharmacogenomics have reported that several single nucleotide polymorphisms (SNPs) of CYP3A5 are correlated with gene expression and enzyme activity. Phenotypes of CYP3A5 are typed as expressors (*1/*1 and *1/*3) or non-expressors (*3/*3) . In living-donor liver transplantation, CYP3A5 phenotypes could predict the blood concentration of tacrolimus. In particular, preoperative assessment of CYP3A5 genotypes in both recipients (intestine) and donors (graft liver) is required for predicting tacrolimus pharmacokinetics. In kidney transplantation, blood tacrolimus concentrations were significantly different between expressors and non-expressors. Genotyping and phenotyping of recipients were useful to predict blood tacrolimus levels in early phase of post-transplantation. Furthermore, phenotypes of CYP3A5 could predict the initial dose of tacrolimus. Combination therapy was performed after bone marrow transplantation to prevent complications. Genotyping and phenotyping of metabolic enzymes for combination dugs would be useful for predicting drug actions. In conclusion, phenotyping based on pharmacogenomics supports personalized medicine in transplantation therapy. In future, multiplex testing should be developed to support personalized medicine in various fields. PMID: 23947183 [PubMed - indexed for MEDLINE]

Nitroxyl donors retain their depressor effects in hypertension.

Related Articles Nitroxyl donors retain their depressor effects in hypertension. Am J Physiol Heart Circ Physiol. 2013 Sep 15;305(6):H939-45 Authors: Irvine JC, Ravi RM, Kemp-Harper BK, Widdop RE Abstract Nitroxyl (HNO), the redox congener of nitric oxide, has numerous vasoprotective actions including an ability to induce vasodilation and inhibit platelet aggregation. Given HNO is resistant to scavenging by superoxide and does not develop tolerance, we hypothesised that HNO would retain its in vivo vasodilatory action in the setting of hypertension. The in vitro and in vivo vasodilator properties of the HNO donors Angeli's salt (AS) and isopropylamine/NONOate (IPA/NO) were compared with the NO donor diethylamine/NONOate (DEA/NO) in spontaneously hypertensive rats (SHR) and normotensive [Wistar-Kyoto (WKY) rats]. AS (10, 50, and 200 μg/kg), IPA/NO (10, 50, and 200 μg/kg), and DEA/NO (1, 5, and 20 μg/kg) caused dose-dependent depressor responses in conscious WKY rats of similar magnitude. Depressor responses to AS and IPA/NO were significantly attenuated (P < 0.01) after infusion of the HNO scavenger N-acetyl-l-cysteine (NAC), confirming that AS and IPA/NO function as HNO donors in vivo. In contrast, responses to DEA/NO were unchanged following NAC infusion. Depressor responses to AS and IPA/NO in conscious SHR retained their sensitivity to the inhibitory effects of NAC (P < 0.01), yet those to DEA/NO in SHR were significantly (P < 0.05) enhanced following NAC infusion. Importantly, depressor responses to AS, IPA/NO, and DEA/NO were preserved in hypertension and vasorelaxation to AS and DEA/NO, in isolated aorta, unchanged in SHR as compared with WKY rats. This study has shown for the first time that HNO donors exert antihypertensive effects in vivo and may, therefore, offer a therapeutic alternative to traditional nitrovasodilators in the treatment of cardiovascular disorders such as hypertension. PMID: 23851276 [PubMed - indexed for MEDLINE]

Scotblood 2012: transfusion/transplant medicine in the 2nd decade of the 21st century.

Related Articles Scotblood 2012: transfusion/transplant medicine in the 2nd decade of the 21st century. Transfus Apher Sci. 2013 Jun;48(3):415-20 Authors: Colligan D, McGowan N, Seghatchian J Abstract Transfusion medicine is a technology-based discipline, undergoing continual changes for improvement. It requires staff at all levels to be continually educated and trained in appropriate multidisciplinary skills, in line with the rapid developments in all areas of transfusion practice: from blood/organ collection, through processing and storage to the more advanced cellular and hospital-based transfusion/transplantation therapies. Whilst the majority of the challenges to improve hospital and general transfusion practice can be overcome through team work, education, timely objectives and perseverance, it is important to envisage opportunities for implementing digital technologies to reduce all of the applicable hazards associated with transfusion. These can vary widely from new and emerging pathogens to limitations of supply due to growing demographic changes in populations. In the first decade of 21st century we have already witnessed unprecedented advances in haematopoietic stem cell transplantation to minimise the toxicities of graft versus host disease (GvHD), and in cell therapy to explore immunotherapy against cancer and other malignant disorders. Today there are 1000 genome project hapmaps that only the extreme cost of their implementation to routine practices may limit. Transfusion medicine, like all disciplines of medicine, nevertheless, will face difficult choices between increasing healthcare technology and increasing worldwide health. Drs. Colligan and McGowan, the new lead organisers of this wonderful yearly educational programme have agreed to follow the previous organisers' strategy to make a summary report of their meeting to become available, through TRASCI to broader interested groups, with the sprit that "sharing is caring". The main highlights of the 2012 conference were: targeting transfusion practices in hospital, a continuing journey; emerging infections and the potential causes and possible remedial actions; building for the future; the challenging issues of donor recruitment/retention; and finally; the application of Information Technology as a decision making tool, utilising clinical audit monitoring to evaluate good practice. This year's conference also coincided with the retirement of Martin Bruce OBE, after his 41years distinguished career, who gave the most delightful and humorous talk of a" life time of learning" which delighted all the participants. Finally, 2012 also marked the retirements of the previous lead Scotblood organisers Prof. Robin Fraser and Dr. Hagop Bessos after over thirty years service to SNBTS, and to whom we would like to dedicate this meeting report and wish them a happy and healthy retirement. This commentary comprises summaries of the presentations, based in part on the abstracts provided by the speakers. PMID: 23643474 [PubMed - indexed for MEDLINE]