Evaluation of testicular cytotoxicity and genotoxicity of sofosbuvir and sofosbuvir - ribavirin in the adult male albino rats

Hepatitis C is a widely distributed problem all over the world, especially Egypt. Chronically infected people develop serious liver disease and now it is the most common cause for liver transplantation. Recently, a new regimen, sofosbuvir (sovaldi), alone or with combinations as sovaldi-ribavirin, was approved for treating this disease. There are limited studies that explore the effects of these drugs on the reproductive organs, and hence affection of male fertility while using these drugs. This study aims to throw more light on whether sovaldi or sovaldi-ribavirin causes testicular damaging effects in the adult male albino rats. We investigated the effect of this regimen in a dose equivalent to that used in the human (41 mg/kg once daily orally for sovaldi and 41 mg/kg twice daily orally for ribavirin) for consecutive 5 and 10 days. There was highly significant decrease in testosterone hormone level and marked degenerative changes in the seminiferous tubules and the testicular interstitium, with increase in collagen deposits in sovaldi treated rats, and in a more extensive manner in sovaldi-ribavirin treated rats. There was a significant increase of deoxyribonucleic acid (DNA) fragmentation in the treated groups after 10 days. However, there was a non-significant difference in DNA fragmentation in the treated groups after 5 days when compared with control. Immuno-histochemistry detection of caspase-3 showed significant increase in its expression in the treated groups after either 5 or 10 days. This denoted the specificity of caspase-3 immunohistochemistry technique in the detection of early apoptotic changes. It was concluded that sovaldi and sovaldi ribavirin induced gonado toxic effects through induction of DNA fragmentation via up regulation of caspase-3, and that the resulting damaging effects increased with longer duration of drug in take

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Protective role of broccoli extract on estradiol valerate-induced polycystic ovary syndrome in female rats

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility. The aim of this study was to investigate the protective role of broccoli extract on estradiol valerate (EV)-induced PCOS in female rats. Forty adult female rats were divided into four main groups; control, broccoli-treated, EV, single intramuscular injection of 16mg/kg)-treated, EV+broccoli (1 g/kg/day)-treated groups. The protected rats were treated orally by gastric tube daily for 4 weeks. At the end of the experiment, blood samples were collected and the ovary were subjected to histological and immunohistochemical analyses. EV treated group exhibited the characteristic features of PCOS. Disturbed ovarian cyclicity in addition to histopathological alterations, including decreased number of healthy follicles and corpora lutea, increased degenerated, cystic follicles and increased collagen fiber deposition were detected by light microscopic studies. Moreover, increased immune-reactivity for iNOS and altered proliferation index were observed by immunohistochemical assessments. Co-adminis-tration of broccoli extract improved EV-induced PCOS in rat model. In conclusion, broccoli may be an effective therapeutic candidate for the treatment of PCOS

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Neuroprotective effect of ginger in the brain of streptozotocin-induced diabetic rats.

Diabetes mellitus results in neuronal damage caused by increased intracellular glucose leading to oxidative stress. Recent evidence revealed the potential of ginger for reducing diabetes-induced oxidative stress markers. The aim of this study is to investigate, for the first time, whether the antioxidant properties of ginger has beneficial effects on the structural brain damage associated with diabetes. We investigated the observable neurodegenerative changes in the frontal cortex, dentate gyrus, and cerebellum after 4, 6, and 8 weeks of streptozotocin (STZ)-induced diabetes in rats and the effect(s) of ginger (500 mg/kg/day). Sections of frontal cortex, dentate gyrus, and cerebellum were stained with hematoxylin and eosin and examined using light microscopy. In addition, quantitative immunohistochemical assessments of the expression of inducible NO synthase (iNOS), tumor necrosis factor (TNF)-α, caspase-3, glial fibrillary acidic protein (GFAP), acetylcholinesterase (AChE), and Ki67 were performed. Our results revealed a protective role of ginger on the diabetic brain via reducing oxidative stress, apoptosis, and inflammation. In addition, this study revealed that the beneficial effect of ginger was also mediated by modulating the astroglial response to the injury, reducing AChE expression, and improving neurogenesis. These results represent a new insight into the beneficial effects of ginger on the structural alterations of diabetic brain and suggest that ginger might be a potential therapeutic strategy for the treatment of diabetic-induced damage in brain.

Reconstruction of the medial patello-femoral and patello-tibial ligaments for treatment of patellar instability.

PURPOSE: The importance of the medial patello-femoral (MPFL) and medial patello-tibial ligaments (MPTL) to the stability of the patella is undoubted. The purpose of this work was to present a technique for the reconstruction of both ligaments and prospectively record its outcome. METHODS: Cadaveric part: the MPFL and MPTL were identified in five knee specimens. Sequential cutting and reattaching of these ligaments were performed to study their effect on patellar stability. CLINICAL PART: In the years between 2005 and 2008, twenty-five knees in twenty-one patients had reconstruction of their MPFL and MPTL using the semitendinosus tendon. In eight of these knees, ligament reconstruction was combined with tibial tubercle osteotomy. The IKDC and Insall's classification of outcome were used for the evaluation of all knees. RESULTS: Cadaveric study revealed that resecting the MPTL increased the lateral translation of the patella up to subluxation at full extension. Intact MPFL avoids full dislocation. Regarding the clinical study, at a minimum 24-months follow-up, all patients reported to have stable patello-femoral joints. There was a significant improvement of the IKDC score 54 ± 2 pre-operatively to 81 ± 2 (Mean ± SD) at 24 months post-operative (P < 0.0003). Nineteen knees scored excellent, five were good and one had fair result. CONCLUSION: A technique for the reconstruction of the MPFL and MPTL that can be performed through minimally invasive approach has been presented and shown to be successful in restoring knee function in cases of traumatic and recurrent patellar dislocation. LEVEL OF EVIDENCE: III.