Immunomodulatory effects of hydroxychloroquine on Th1/Th2 balance in women with repeated implantation failure.

BACKGROUND: Cellular immune abnormalities such as the imbalance between T-helper (Th) 1 and Th2 cytokines have been implicated as potentially modifiable causes of idiopathic repeated implantation failures (RIF). The purpose of this study was to investigate the effects of hydroxychloroquine on IL-10 and TNF-α secretion, expression of T-bet and GATA-3 transcription factors and cellular localization of TNF-α, IFN-γ, IL-10 and IL-4 in endometrial cells in women with RIF. MATERIALS AND METHODS: A total of 17 women with a history of RIF and elevated TNFα/IL-10 ratio (TNFα/IL-10> = 30.6) were included in the study. The serum levels of TNFα and IL-10, the expression of transcription factors related to Th1 and Th2 cells and the immune-reactivity of TNFα, IFN-γ as Th1 related cytokines and IL-10, IL-4 as Th2 related cytokines in endometrial tissues were evaluated by ELISA, real-time PCR, and fluorescent immunohistochemistry respectively. All, evaluations were done both before and after treatment with hydroxychloroquine (400 mg/orally per day). RESULTS: Hydroxychloroquine treatment significantly decreased (p < 0.0001) serum level of TNF-α and significantly increased serum level of IL-10 (p < 0.0001). T-bet, the Th1 transcription factor, expression was down-regulated and GATA-3, the Th2 transcription factor, expression was up-regulated. IL-10 and IL-4 fluorescent immunoreactivities significantly increased (p < 0.05 and p < 0.001 respectively) and TNFα and IFN-γ fluorescent immunoreactivities significantly decreased (p < 0.05) in endometrial tissue in women with RIF after treatment in comparison with before treatment. CONCLUSION: Hydroxychloroquine administration in women with RIF With a high TNF-α/IL-10 ratio during the implantation window can decrease this ratio and seems to be an effective therapeutic strategy in RIF caused by cellular immune abnormalities through a shift in Th2 responses.

Effect of metformin on germ cell-specific apoptosis, oxidative stress and epididymal sperm quality after testicular torsion/detorsion in rats.

The study was designed to evaluate the effects of metformin on apoptosis and epididymal sperm quality in a rat testicular ischaemia/reperfusion (I/R) injury model. A total of 72 male rats were divided into four groups (n = 18 for each group): group 1 (sham-operated group), group 2 (metformin group), group 3 (torsion/detorsion [T/D] + saline) and group 4 (T/D + 300 mg kg-1 metformin). Testicular torsion was achieved by rotating the right testis 720° in a clockwise direction for 1 hr. Tissue malondialdehyde (MDA) level and caspase-3 activity increased and the activities of catalase, superoxide dismutase and glutathione peroxidase decreased in comparison with sham-operated group 4 hr after detorsion (p < .001). In six rats of each group 24 hr after detorsion, histopathological changes and germ cell apoptosis were significantly deteriorated by measuring mean of seminiferous tubule diameters (MSTD) and TUNEL test. Moreover, 30 days after T/D, sperm concentration and motility were examined in six animals per group. Metformin pre-treatment reduced MDA and caspase-3 levels and normalised antioxidant enzyme activities 4 hr after detorsion, and germ cell apoptosis was significantly decreased, and the MSTD, as well as sperm functions, was significantly improved. Reduction in oxidative stress and apoptosis may have a major role in cytoprotective effects of metformin.

Antibacterial effects of Iranian Mentha pulegium essential oil on isolates of Klebsiella sp.

The aim of the present study was the evaluation of the antibacterial activity of Mentha pulegium essential oil on isolates of Klebsiella. Thirty nine isolates were collected from urine specimens submitted to two educational hospitals in Urmia, Iran. The susceptibility of isolates was determined using a broth microdilution method. Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of isolates to Mentha pulegium essential oil were determined. The susceptibilities of isolates to different antibiotics were tested using agar disk diffusion method. The rates of resistance were determined to antibiotics as follows: gentamicin 46.1%, tobramycin 48.7%, ceftizoxime 41%, co-trimoxazole 46.1%, amikacin 33.3%, cephtazidime 51.3%, ciprofloxacin 30.8%, kanamycin 53.8%, nalidixic acid 30.8% ampicillin 79.5% and nitrofurantoin 41%. Mentha pulegium essential oil possessed antibacterial effect against all isolates of Klebsiella sp. with MIC and MBC values in the range of 1.9 x 10(-3) to 4.9 x 10(-4) mm3 mm(-3). In this study clinical isolates of Klebsiella sp. showed very high resistance to tested antibiotics. These results suggest the potential use of the Mentha pulegium essential oil for the control of multi-drug resistant Klebsiella sp. infections. However, more adequate toxicological study must be carried out to verify the possibility of using it for fighting microorganisms in human.