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Introduction: Diabetic nephropathy (DN) is one of most prevalent diabetic complication. It remains unclear whether the anti-inflammatory Hydroxytyrosol (HT) has beneficial effects on biogenesis of diabetic renal changes. So, we aimed to find out the relationship between inflammation, apoptosis, oxidative stress and the progression of DN. Also, try to assess the possible effects of HT on diabetic renal tissue. Materials and Methods: Rats were divided into: non-diabetic rats (group I) and rats with induced type II diabetes that were subdivided into: group II non-treated DM, group III treated with HT, group IV treated with glyclazide and group V treated with combined treatment. Treatments were supplied for eight weeks. Results: Administration of HT alone or with GLY significantly lowered blood glucose levels and ameliorated kidney hypertrophy index together with improving renal dysfunction parameters including creatinine in serum and urine, blood urea nitrogen, serum and urinary albumin, together with the tissue oxidative markers and inflammatory cytokines activities compared to diabetic group. These effects of HT were also reflected on histologic evaluation and Nrf2- Keap1 system expression. Conclusion: This study discovers the renoprotective effect of HT in diabetic rats. Hence, this study recommended an addition of antioxidants like HT to the management of diabetes.

It has been proposed that many factors have been implicated in the pathogenesis of unexplained recurrent spontaneous miscarriage (URSM). The objective of this study was to evaluate the levels of some antioxidants, tumor necrosis factor-alpha (TNF-alpha), luteinizing (LH) and follicle-stimulating hormone (FSH) in URSM. Serum levels of superoxide dismutase (SOD), catalase (CAT), LH, FSH as well as TNF-alpha in serum and the expression of TNF-alpha positive cells in placental tissues, were assayed in women suffering from unexplained first trimester miscarriage. Two groups were included, the first was represented by 16 women with URSM (number of abortions: 3-5) and the second one included 24 women with URSM (number of abortions5). The control groups included 20 women within their first trimester of pregnancy and 20 non pregnant healthy females within their follicular phase. The obtained results showed a highly significant decrease in serum levels of SOD and CAT, in the URSM groups compared to control groups (p0.05 for each comparison). Higher serum levels of TNF-alpha were detected in URSM groups compared to control groups (p0.05 for each comparison). A significant increase in serum levels of LH was encountered between URSM groups compared to control groups; on the other hand the mean levels of FSH expressed no significant changes among URSM groups as compared to first trimester pregnancies control group. A positive correlation was noticed between serum levels of TNF-alpha and the levels of LH (p0.05). We conclude that antioxidant enzymes (CAT, SOD), TNF-alpha, LH and FSH may play a major role in the pathogenesis of URSM. Much more work is required before the mechanisms, which lead to RSM, can be fully understood.

BACKGROUND: Many factors have been implicated in the pathogenesis of unexplained recurrent spontaneous miscarriage (URSM). METHODS: The objective of this preliminary clinical study was to verify whether intravaginal sildenafil citrate tablets (25 mg intravaginally 4 times/day for 24 days) are effective as a novel treatment of threatened miscarriage in patients with a history of URSM (n=4). We also evaluated changes in the concentrations of some antioxidants the percent expression of cells positive for tumor necrosis factor-alpha (TNF-alpha) CD56+T-cells [CD3+CD56+ natural killer cells (NKT cells) (cluster differentiation 3 56 NKT cells)] which express one of the NK cell markers and uterine artery pulsatility index (PI). We compared these results with healthy women in their first trimester of pregnancy (FTP n=4). RESULTS: Sildenafil improved the measured antioxidants concentrations [total antioxidant capacity (TAC) glutathione S-transferase (GSH-S-T) and catalase (CAT) superoxide dismutase (SOD)] and improved oxidative stress by reducing malondialdehyde (MDA) and nitric oxide (NO) in the four patients under investigation. The improvement in antioxidants was close to concentrations seen in women in their FTP. The four patients had progressed to their third trimester of pregnancy using this novel application. The percentage of [CD3+CD56+ NKT cells] and TNF-alpha in peripheral blood was higher in URSM patients compared to women in their FTP. However concentrations were greatly reduced and improved after sildenafil administration. We demonstrated that intravaginal sildenafil citrate tablets can reduce vasoconstriction by increasing blood flow through relaxation of uterine arteries as indicated from measured PI in URSM patients. CONCLUSIONS: We conclude that intravaginal sildenafil citrate tablets used as suppositories might be a novel interesting safe antiabortive option in the treatment of threatened miscarriage in patients with a history of URSM. We are the first to report this novel clinical application in four case reports in Egypt.