effect of exposure to low levels of chlorine gas on the pulmonary function and symptoms in a Chloralkali unit

Background: the present study was undertaken to ascertain whether [or not] long term occupational exposure to low [sub-TLV levels] atmospheric concentrations of chlorine gas was associated with any significant decrements in the parameters of pulmonary function and/or increased prevalence of respiratory symptoms

Methods: in this retrospective cohort study that was performed in 2012, 54 workers of a local chloralkali unit and 38 non-exposed office staff were enrolled and compared. Atmospheric concentrations of chlorine gas were measured by numerous sampling with gas detector tubes. Data on respiratory symptoms were gathered using a standard questionnaire. Furthermore, spirometry test was performed for subjects both prior to and at the end of shift

Results: mean atmospheric concentration of chlorine gas was 0.27 +/- 0.05 ppm that was lower than the existing TLV value for this toxic irritant gas. Symptoms of respiratory diseases were significantly more frequent among exposed subjects than in referent individuals. Additionally, mean values of most parameters of pulmonary function including FEV1 [P=0.031], FEV1/FVC ratio [P=0.003] and PEF [P=0.005] were significantly lower than their corresponding values for unexposed subjects. Additional cross shift decrements were also noted in some lung functional capacities, although changes were not statistically significant

Conclusions: exposure to sub-TLV levels of chlorine gas is associated with statistically significant decrements in the parameters of pulmonary function as well as increased prevalence of respiratory symptoms

Autophagy-modulated human bone marrow-derived mesenchymal stem cells accelerate liver restoration in mouse models of acute liver failure

Background: Mesenchymal stem cells [MSCs] have been recently received increasing attention for cell-based therapy, especially in regenerative medicine. However, the low survival rate of these cells restricts their therapeutic applications. It is hypothesized that autophagy might play an important role in cellular homeostasis and survival. This study aims to investigate the regenerative potentials of autophagy-modulated MSCs for the treatment of acute liver failure [ALF] in mice

Methods: ALF was induced in mice by intraperitoneal injection of 1.5 ml/kg carbon tetrachloride. Mice were intravenously infused with MSCs, which were suppressed in their autophagy pathway. Blood and liver samples were collected at different intervals [24, 48 and 72 h] after the transplantation of MSCs. Both the liver enzymes and tissue necrosis levels were evaluated using biochemical and histopathological assessments. The survival rate of the transplanted mice was also recorded during one week

Results: Biochemical and pathological results indicated that 1.5 ml/kg carbon tetrachloride induces ALF in mice. A significant reduction of liver enzymes and necrosis score were observed in autophagy-modulated MSC-transplanted mice compared to sham [with no cell therapy] after 24 h. After 72 h, liver enzymes reached their normal levels in mice transplanted with autophagy-suppressed MSCs. Interestingly, normal histology without necrosis was also observed

Conclusion: Autophagy suppression in MSCs ameliorates their liver regeneration potentials due to paracrine effects and might be suggested as a new strategy for the improvement of cell therapy in ALF

Down-regulation of the autophagy gene, ATG7, protects bone marrow-derived mesenchymal stem cells from stressful conditions

BACKGROUND: Mesenchymal stem cells (MSCs) are valuable for cell-based therapy. However, their application is limited owing to their low survival rate when exposed to stressful conditions. Autophagy, the process by which cells recycle the cytoplasm and dispose of defective organelles, is activated by stress stimuli to adapt, tolerate adverse conditions, or trigger the apoptotic machinery. This study aimed to determine whether regulation of autophagy would affect the survival of MSCs under stress conditions. METHODS: Autophagy was induced in bone marrow-derived MSCs (BM-MSCs) by rapamycin, and was inhibited via shRNA-mediated knockdown of the autophagy specific gene, ATG7. ATG7 expression in BM-MSCs was evaluated by reverse transcription polymerase chain reaction (RT-PCR), western blot, and quantitative PCR (qPCR). Cells were then exposed to harsh microenvironments, and a water-soluble tetrazolium salt (WST)-1 assay was performed to determine the cytotoxic effects of the stressful conditions on cells. RESULTS: Of 4 specific ATG7-inhibitor clones analyzed, only shRNA clone 3 decreased ATG7 expression. Under normal conditions, the induction of autophagy slightly increased the viability of MSCs while autophagy inhibition decreased their viability. However, under stressful conditions such as hypoxia, serum deprivation, and oxidative stress, the induction of autophagy resulted in cell death, while its inhibition potentiated MSCs to withstand the stress conditions. The viability of autophagy-suppressed MSCs was significantly higher than that of relevant controls (P<0.05, P<0.01 and P<0.001). CONCLUSION: Autophagy modulation in MSCs can be proposed as a new strategy to improve their survival rate in stressful microenvironments.

[Effects of doxepin on physiology of reproduction in adult male rats]

Doxepin is a serotonin and norepinephrine reuptake inhibitor. Considering the importance of this drug in treating some nervous diseases, its side effects seem to be important on the endocrine axis. In this study, the effects of doxepin on the concentration of testosterone, FSH and LH level and spermatogenesis were studied. This experimental study was done on 40 male Wistar rats that were divided into 5 groups of 8. The control group received nothing. The sham group was given distilled water as a solvent. The experimental groups were injected 35, 70 and 140 mg/kg of the drug orally for 21 days, respectively. The blood samples were taken at 22[th] day and the concentration of testosterone, FSH and LH were measured by RIA method. In addition, at the 22[th] day, the testes were separated and histological changes were studied among experimental, sham and control groups. The results were evaluated by using ANOVA and Duncan tests. The results showed that 140 mg/kg of doxepin reduced serum testosterone level, while it increased FSH and LH levels [p<0.05]. Histological investigations of the testes showed a decline on spermatogenesis chain in dose of 140 mg/kg of the drug. This study showed that doxepin decreases the concentration of testosterone level and the number of spermatogenic cells and increases FSH and LH levels at high doses. Therefore, it may weaken the function of reproductive activity