OBJECTIVE:In the post-sternotomy mediastinitis patients, Staphylococcus aureus is the pathogenic microorganism encountered most often. In our study, we aimed to determine the efficacy of antibiotic treatment with vancomycin and tigecycline, alone or in combination with hyperbaric oxygen treatment, on bacterial elimination in experimental S. aureus mediastinitis.

METHODS:Forty-nine adult female Wistar rats were used. They were randomly divided into seven groups, as follows: non-contaminated, contaminated control, vancomycin, tigecycline, hyperbaric oxygen, hyperbaric oxygen + vancomycin and hyperbaric oxygen + tigecycline. The vancomycin rat group received 10 mg/kg/day of vancomycin twice a day through intramuscular injection. The tigecycline group rats received 7 mg/kg/day of tigecycline twice a day through intraperitoneal injection. The hyperbaric oxygen group underwent 90 min sessions of 100% oxygen at 2.5 atm pressure. Treatment continued for 7 days. Twelve hours after the end of treatment, tissue samples were obtained from the upper part of the sternum for bacterial count assessment.

RESULTS:When the quantitative bacterial counts of the untreated contaminated group were compared with those of the treated groups, a significant decrease was observed. However, comparing the antibiotic groups with the same antibiotic combined with hyperbaric oxygen, there was a significant reduction in microorganisms identified (P<0.05). Comparing hyperbaric oxygen used alone with the vancomycin and tigecycline groups, it was seen that the effect was not significant (P<0.05).

CONCLUSION:We believe that the combination of hyperbaric oxygen with antibiotics had a significant effect on mediastinitis resulting from methicillin-resistant Staphylococcus aureus. Methicillin-resistant Staphylococcus aureus mediastinitis can be treated without requiring a multidrug combination, thereby reducing the medication dose and concomitantly decreasing the side effects.

OBJECTIVE:To investigate the therapeutic effects of acupuncture combined with nerve block for treatment of lumbar disc herniation.

METHODS:Ninety cases of lumbar disc herniation were randomly divided into three groups: acupuncture combined with nerve block group, acupuncture group and nerve block group, 30 cases in each group. The acupuncture combined with nerve block group was treated with acupuncture combined with nerve block therapy, L2-L5 Jiaji (EX-B 2), Zhibian (BL 54), Huantiao (GB 30), Yanglingquan (GB 34) etc. were selected for acupuncture, affected nerve root, sciatic nerve or common peroneal nerve were selected for nerve block with anti-inflammation-analgesic injection; the acupuncture group was treated with acupuncture only; the nerve block group was treated with nerve block only. After 4 weeks of treatment, the visual analogue scale (VAS), Oswestry lumbar dysfunction index (ODI) and modified MacNab standard were compared to evaluate the therapeutic effects of three groups.

RESULTS:The VAS and ODI in all groups were significantly decreased after one week, two weeks and four weeks of treatment (all P<0.01); after one week of treatment, the scores of VAS and ODI in nerve block group and acupuncture combined with nerve block group were significantly lower than those of acupuncture group (P<0.05); after two weeks and four weeks of treatment, the scores of VAS and ODI in acupuncture combined with nerve block group were significantly lower than those of acupuncture group and nerve block group (P<0.05). The effective rate and excellent and good rate of the acupuncture combined with nerve block group were significantly higher than those of acupuncture group and nerve block group (both P<0.01).

CONCLUSION:The nerve block therapy and acupuncture are effective methods for treatment of lumbar disc herniation, while it has a better effect when these two treatments are combined used.

OBJECTIVE:To investigate the therapeutic effects of acupuncture combined with nerve block for treatment of lumbar disc herniation.

METHODS:Ninety cases of lumbar disc herniation were randomly divided into three groups: acupuncture combined with nerve block group, acupuncture group and nerve block group, 30 cases in each group. The acupuncture combined with nerve block group was treated with acupuncture combined with nerve block therapy, L2-L5 Jiaji (EX-B 2), Zhibian (BL 54), Huantiao (GB 30), Yanglingquan (GB 34) etc. were selected for acupuncture, affected nerve root, sciatic nerve or common peroneal nerve were selected for nerve block with anti-inflammation-analgesic injection; the acupuncture group was treated with acupuncture only; the nerve block group was treated with nerve block only. After 4 weeks of treatment, the visual analogue scale (VAS), Oswestry lumbar dysfunction index (ODI) and modified MacNab standard were compared to evaluate the therapeutic effects of three groups.

RESULTS:The VAS and ODI in all groups were significantly decreased after one week, two weeks and four weeks of treatment (all P<0.01); after one week of treatment, the scores of VAS and ODI in nerve block group and acupuncture combined with nerve block group were significantly lower than those of acupuncture group (P<0.05); after two weeks and four weeks of treatment, the scores of VAS and ODI in acupuncture combined with nerve block group were significantly lower than those of acupuncture group and nerve block group (P<0.05). The effective rate and excellent and good rate of the acupuncture combined with nerve block group were significantly higher than those of acupuncture group and nerve block group (both P<0.01).

CONCLUSION:The nerve block therapy and acupuncture are effective methods for treatment of lumbar disc herniation, while it has a better effect when these two treatments are combined used.

The aim of this study was to assess the effects of an aerobic training program as complementary therapy in patients suffering from moderate depression. 82 female patients weredivided into a group that received traditional pharmacotherapy (Fluoxetine 20 mg) and a group that received pharmacotherapy plus an aerobic training program. This program was carried out for eight consecutive weeks, three days per week, and included gymnastics, dancing, and walking. Depressive symptoms were measured with the Beck Depression Inventory and the ICD-10 Guide for Depression Diagnosis, both administered before and after treatments. The results confirm the effectiveness of the aerobic training program as a complementary therapy to diminish depressive symptoms in patients suffering from moderate depression.

CONTEXT: Limited information exists on the interaction between diet and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and the interaction's effect on serum lipid and lipoprotein levels, insulin sensitivity, and circulating antioxidant vitamin and provitamin levels. OBJECTIVE: To evaluate the separate and combined effects of diet and simvastatin therapy on serum levels of lipids, lipoproteins, antioxidants, and insulin.

DESIGN, SETTING, AND PARTICIPANTS: Randomized, controlled crossover trial conducted from August 1997 to June 1998 in 120 previously untreated hypercholesterolemic men aged 35 to 64 years who were recruited from the community in Turku, southwestern Finland.

INTERVENTIONS: After a 4- to 6-week placebo run-in period, participants were randomly allocated to a habitual diet (n = 60) or dietary treatment group (n = 60), and each of these groups was further randomized in a double-blind crossover fashion to receive simvastatin (20 mg/d) or placebo, each for 12 weeks (n = 30 in each group). The main goals of the dietary treatment were to reduce energy intake from saturated plus trans-unsaturated fats to no more than 10% by replacing them partly with monounsaturated and polyunsaturated fats rich in omega-3 fatty acids and to increase intake of fruits, vegetables, and dietary fiber.

MAIN OUTCOME MEASURES: Changes in levels of total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol; triglycerides; apolipoprotein B; insulin; glucose; and antioxidants at week 12 of each treatment period, compared among the 4 groups.

RESULTS: Dietary treatment decreased levels of total cholesterol by 7.6% (P<.001), LDL cholesterol by 10.8% (P<.001), HDL cholesterol by 4.9% (P =.01), apolipoprotein B by 5.7% (P =.003), serum insulin by 14.0% (P =.02), and alpha-tocopherol by 3.5% (P =.04). Simvastatin decreased levels of total cholesterol by 20.8%, LDL cholesterol by 29.7%, triglycerides by 13.6%, apolipoprotein B by 22.4%, alpha-tocopherol by 16.2%, beta-carotene by 19.5%, and ubiquinol-10 by 22.0% (P<.001 for all) and increased levels of HDL cholesterol by 7.0% (P<.001) and serum insulin by 13.2% (P =.005). Glucose levels remained unchanged in all groups. The effects of dietary treatment and simvastatin were independent and additive.

CONCLUSIONS: A modified Mediterranean-type diet rich in omega-3 fatty acids efficiently potentiated the cholesterol-lowering effect of simvastatin, counteracted the fasting insulin-elevating effect of simvastatin, and, unlike simvastatin, did not decrease serum levels of beta-carotene and ubiquinol-10.

Although hyperthermia offers clinical appeal to sensitize cells to chemotherapy, this approach has been limited in terms of long-term outcome as well as economic and technical burden. Thus, a more detailed knowledge about how hyperthermia exerts its effects on chemotherapy may illuminate ways to improve the approach. Here we asked whether hyperthermia alters the response to chemotherapy-induced DNA damage and if this mechanism is involved in its sensitizing effect, in BRCA-competent models of ovarian and colon cancer. Notably, we found that hyperthermia delayed the repair of DNA damage caused by cisplatin or doxorubicin, acting upstream of different repair pathways to block histone polyADP-ribosylation (PARylation), a known effect of chemotherapy. Further, hyperthermia blocked this histone modification as efficiently as pharmacological inhibitors of polyADP-ribosyl polymerase (PARPi), producing comparable delay in DNA repair, induction of double strand breaks (DSB) and cell cytotoxicity after chemotherapy. Mechanistic investigations indicated that inhibiting PARylation by either hyperthermia or PARPi induced lethal DSB upon chemotherapy treatment, not only by reducing DNA repair but also by preventing replication fork slowings. Overall, our work reveals how PARP blockade - either by hyperthermia or small molecule inhibition - can increase chemotherapy-induced damage in BRCA-competent cells.

The purpose of this study was to verify that a combination of mild hyperthermia and docetaxel chemotherapy produces synergistic antitumor effects and to explore the action mechanisms of this treatment approach. The effects of docetaxel on the proliferation of cells from the estrogen receptor (ER)-positive human breast cancer cell line MCF-7 and the ER-negative human breast cancer cell line MDA-MB-453 were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and effective experimental concentrations of docetaxel were determined. The effects of mild hyperthermia plus docetaxel therapy on apoptosis rate in the MCF-7 and MDA-MB-453 human breast cancer cell lines were analyzed by using flow cytometry with Annexin-V fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining. The effects of these combined treatments on cell cycle progression in the MCF-7 and MDA-MB-453 human breast cancer cell lines were examined by using flow cytometry. The effects of these combined treatments on the expression of apoptosis-related proteins and proteins in the mitogen-activated protein kinase (MAPK) pathways were analyzed by using Western blotting. The effects of these combined treatments on the expression of the heat shock protein 70 (HSP70) and the multi-drug resistance (MDR) gene product P-glycoprotein (Pgp) were examined by using Western blotting. The results showed that the half-maximal inhibitory concentration (IC50) of docetaxel for MCF-7 and MDA-MB-453 cells was 19.57±1.12 and 21.64±2.31 μmol/L respectively. Mild hyperthermia with docetaxel therapy could increase apoptosis rate in the MCF-7 and MDA-MB-453 cells. Apoptosis rate in MCF-7 and MDA-MB-453 cells was increased from (23.66±3.59)% and (18.51±3.17)% in docetaxel treatment group to (47.12±6.73)% and(55.16±7.42)% in mild hyperthermia plus docetaxel group, indicating that the mild hyperthermia and docetaxel therapeutic approaches exhibited significant synergistic antitumor effects. Treatments of mild hyperthermia plus docetaxel induced G2/M cell cycle arrest in the MCF-7 and MDA-MB-453 cells. Western blotting demonstrated that proteins in the MAPK pathway were expressed at higher levels in docetaxel-treated cells following mild hypothermia than those in cells treated with docetaxel alone. As compared with blank control group, cells from the mild hyperthermia plus docetaxel group exhibitedsignificantly decreased B-cell lymphoma 2 (Bcl-2) protein expression but slightly increased Bcl-2-associated X protein (Bax) expression. Western blotting results revealed that HSP70 and Pgp expression levels were significantly increased following mild hypothermia. It was concluded that treatments of mild hyperthermia plus docetaxel inhibited the proliferation of human breast cancer cells, promoted apoptosis of breast cancer cells, and produced synergistic antitumor effects.

Chronic Pseudomonas aeruginosa lung infection is the most severe complication in cystic fibrosis patients. It is characterised by antibiotic-tolerant biofilms in the endobronchial mucus with zones of oxygen (O2) depletion mainly due to polymorphonuclear leucocyte activity. Whilst the exact mechanisms affecting antibiotic effectiveness on biofilms remain unclear, accumulating evidence suggests that the efficacy of several bactericidal antibiotics such as ciprofloxacin is enhanced by stimulation of the aerobic respiration of pathogens, and that lack of O2 increases their tolerance. Reoxygenation of O2-depleted biofilms may thus improve susceptibility to ciprofloxacin possibly by restoring aerobic respiration. We tested such a strategy using reoxygenation of O2-depleted P. aeruginosa strain PAO1 agarose-embedded biofilms by hyperbaric oxygen treatment (HBOT) (100% O2, 2.8bar), enhancing the diffusive supply for aerobic respiration during ciprofloxacin treatment. This proof-of-principle study demonstrates that biofilm reoxygenation by HBOT can significantly enhance the bactericidal activity of ciprofloxacin on P. aeruginosa. Combining ciprofloxacin treatment with HBOT thus clearly has potential to improve the treatment of P. aeruginosa biofilm infections.

OBJECTIVE:To study the synergistic effect of thermotherapy and chemotherapy with chemotherapy on lung tumor cell growth in order to explore its underlying mechanisms.

METHODS:A549 cells were treated by combination of 43 degrees C and 50 microg/L Paclitaxel, and 43 degrees C or 50 microg/L Paclitaxel alone. MTU assay and Wound-healing assay were used to measure the survival and the invasive capacity. Phosphorylation of JNK and expression of HSP70 were determined with Western Blotting. Cells without treatment were used as controls.

RESULTS:In comparison with cells treated with 43 degrees C and 50 microg/L Paclitaxel alone, or with combination of 43 degrees C and 50 microg/L Paclitaxel and SP600125, the proliferation rate of cells subjected to combination treatment of 43 degrees C and 50 microg/L Paclitaxel decreased significantly (P>0.05). There were no significant differences in cell proliferation between untreated cells and the cells treated with 43 degrees C heat, 50 microg/L Paclitaxel and SP600125 (P>0.05). The invasive capacities of the cells treated combination of 43 degrees C heat and 50 microg/L Paclitaxel were markedly reduced in comparison to other treatment groups. Also phosphorylations of JNK were significantly elevated in comparison to untreated cells or the cells only underwent chemotherapy (P<0.05). The expression levels of HSP70 on thermotherapy in combination with chemotherapy were more lower than those in thermotherapy group (P<0.05).

CONCLUSION:Thermotherapy in combination with chemotherapy showed more strong inhibitory effect than those of thermotherapy or chemotherapy alone on lung tumor cell growth. The resultant phosphorylation of JNK and inhibition of HSP70 expression could be responsible for this effect.