Beneficial effects of Cyclosporine A in combination with Nortriptyline on germ cell-specific apoptosis, oxidative stress and epididymal sperm qualities following testicular ischemia/reperfusion in rats: a comparative study.

BACKGROUND: Testicular torsion is a pathological condition which needs emergency surgical intervention. However, after surgical reperfusion, oxidative stress factors cause to germ cell apoptosis. The study was planned to evaluate the efficacy of simultaneous use of Cyclosporine A (CsA) and Nortriptyline (Nort) to repair testicular damages in an experimental torsion/detorsion (T/D) rat model. METHODS: Male rats (n = 112) were allocated into 7 groups 16 each in; (Group 1); Control group, (Group 2); T/D group, (Group 3-4); CsA 1 and 5 mg/kg, (Group 5-6); Nort 2 and 10 mg/kg and (Group 7); concurrent group, CsA (1 mg/kg) + Nort (2 mg/kg). Right uni-lateral torsion was inducted by twisting testis 720 degrees in the clockwise direction for 1 h. For short-term and mid-term studies, lipid peroxidation, antioxidant enzyme activities, caspase-3 level, histopathological changes and germ cell apoptosis were evaluated. Moreover, in long-term investigation, semen analysis was performed. RESULTS: After T/D induction, testis abnormalities both functional and structural were appeared. Pre- and post-treatment with CsA and Nort, separately, reduced MDA and caspase-3 levels, normalized antioxidant levels, ameliorate tissue injury and improved sperm criteria. CONCLUSION: The antioxidant and anti-apoptotic characteristics of CsA and Nort and their protective effects have been shown in our study. Concurrent administration of CsA and Nort in selected low-dose indicated a significant positive effect as compared to the individual drug interventions on the reversal of T/D induced oxidative stress in short-term, apoptosis, and histologic changes in mid-term, as well as semen criteria in the long-term appraisal.

Isolation and characterization of lytic bacteriophages against Pseudomonas aeruginosa isolates from human infections in the north-west of Iran.

Background and Objectives: With the emergence of Pseudomonas aeruginosa antibiotic-resistant strains, using the anti-bacterial potential of bacteriophages could be an effective approach to combat bacterial infections. Materials and Methods: In this study, after evaluation of antibiotic sensitivity of 20 clinical bacterial isolates of Pseudomonas aeruginosa, isolation of lytic phages was performed against 15 isolates using double-layer agar overlay technique. Molecular analysis of isolated phages was carried out using EcoRV and HindIII endonucleases. Then, the host range of the phages was evaluated and the phage with the broadest host range (PPaMa1/18) was selected to morphological characteristics by TEM. Also, its one-step growth curve was determined and the stability of the phage to environmental parameters (temperature and pH) was evaluated. Results: All isolates of Pseudomonas aeruginosa were resistant to five antibiotics. In total, 15 phages were successfully isolated from the sewage sources against each of 15 used bacterial isolates. Molecular analysis of the phages showed a high rate of genomic variation. In the morphological analysis of the selected phage (PPaMa1/18) using TEM, an icosahedral head with a size of 90 nm × 75 nm and a long contractile tail (215 nm) were observed which indicated its similarity to the Myoviridae family. The latent period of the PPaMa1/18 was about 20 minutes and its burst size was estimated to be 58 PFU/cell. Also, the PPaMa1/18 phage antibacterial activity was not significantly affected at pH 4-10 and temperature 4-40C°. Conclusion: Findings demonstrated that isolated bacteriophage (PPaMa1/18) with wide host range, strong lytic effect and high stability can be used as a promising candidate for the treatment of antibiotic-resistant infections caused by Pseudomonas aeruginosa.

Comparison of multiple doses of cyclosporine A on germ cell apoptosis and epididymal sperm parameters after testicular ischemia/reperfusion in rats.

Testicular torsion/detorsion (T/D) is an inflammatory problem in men genital system with infertility effects. Cyclosporine A (CsA) as an immunosuppressant medication, exerts anti-inflammatory properties in tissue injuries. We sought to compare the efficacy of 3 doses of CsA on oxidative stress, apoptosis and epididymal sperm quality after ipsilateral testicular T/D. METHODS: 96 mature male rats were divided into six groups 16 each in: Control group (Group1), Sham operated (Group2), In rest groups, the right testis was twisted 720° in a clockwise direction for 1 h; T/D + 0.1% dimethylsulfoxide) DMSO((Group3), and in groups 4-6; CsA were administered 1, 5, and 10 mg/kg, intravenously (iv) 30 and 90 min after torsion, respectively. RESULTS: Tissue malondialdehyde (MDA) level and caspase-3 activity increased and catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities decreased in compared with control group 4 h after detorsion (p < .001). In six rats of each group 24 h after detorsion, histopathological changes and germ cell apoptosis were significantly deteriorated by determining mean of seminiferous tubules diameters (MSTD) and TUNEL assay. Moreover, 30 days after T/D, sperm concentration and motility were examined in rest of animals. CONCLUSIONS: Pre- and post-reperfusion CsA diminished MDA and caspase-3levels and normalized antioxidant enzymes activities. Germ cell apoptosis was significantly reduced, as well as, MSTD and long-term sperm insults were improved. Inhibition of mitochondrial permeability transition pore opening is suggested mechanism for cell protection against testicular T/D insults.