Intracavernous Injection of Human Umbilical Cord Blood Mononuclear Cells Improves Erectile Dysfunction in Streptozotocin-Induced Diabetic Rats.

INTRODUCTION: Erectile dysfunction (ED) worsens in men with diabetes. Human umbilical cord blood (HUCB), because of its widespread availability and low immunogenicity, is a valuable source for stem cell-based therapies. AIM: To determine the effect of intracavernous injection of HUCB mononuclear cells (MNCs) on ED in rats with diabetes induced by streptozotocin. METHODS: Thirty adult male Sprague-Dawley rats were equally divided into three groups: (i) control, (ii) diabetes induced by streptozotocin (35 mg/kg intravenously for 8 weeks), and (iii) diabetic rats treated with MNCs (1 × 106 cells by intracavernosal injection). The HUCB-MNCs isolated by the Ficoll-Hypaque technique were obtained from eight healthy donors and administered to diabetic rats after 4 weeks. MAIN OUTCOME MEASURES: The ratio of intracavernosal pressure to mean arterial pressure ratio; the protein expression of endothelial and neuronal markers, such as von Willebrand factor, neuronal nitric oxide synthase, hypoxia-inducible factor-1α, and vascular endothelium growth factor; and the relative area of smooth muscle to collagen using western blotting and Masson trichrome staining were determined. RESULTS: Diabetic rats demonstrated a significantly decreased ratio of intracavernosal pressure to mean arterial pressure (0.26 ± 0.04; P < .01) and treatment with MNCs restored erectile function in diabetic rats (0.67 ± 0.05) compared with control rats (0.56 ± 0.02). In bath studies, neurogenic relaxant and contractile responses were significantly decreased in diabetic cavernosal tissues, which were restored by treatment. The ratio of smooth muscle to collagen was partly recovered by treatment, whereas von Willebrand factor levels were not altered in any group. Neuronal nitric oxide synthase and vascular endothelium growth factor levels were decreased, which were not restored by treatment. Increased hypoxia-inducible factor-1α protein expression in the diabetic group was completely normalized in MNC-treated diabetic samples. CONCLUSION: These results suggest that HUCB-MNC treatment can enhance the recovery of erectile function and promote numerous activities such the contribution of the hypoxia-inducible factor-1α and von Willebrand factor pathway to the neurogenic erectile response of diabetic rats. HUCB-MNCs in the healing process could involve an adaptive regenerative response and appear to be a potential candidate for cell-based therapy in ED of men with diabetes. It is evident that HUCB could provide a realistic therapeutic modality for the treatment of diabetic ED.

Vitamin C is effective for the prevention and regression of endometriotic implants in an experimentally induced rat model of endometriosis.

OBJECTIVE: Endometriosis is a chronic inflammatory disease pathologically defined as the presence of endometrial-like tissue outside the uterine cavity. It is one of the most important diseases affecting women of reproductive age. The process of endometriotic implant growth is mediated by many complex interactions of immunologic, hormonal, genetic, and environmental mediators. Vitamin C (ascorbic acid), besides playing a role in preventing invasion and metastasis, is an antioxidant having anti-inflammatory and -angiogenic effects. In this study, we aimed to investigate the effect of vitamin C on the prevention and regression of endometriotic implants in a rat model of endometriosis. MATERIALS AND METHODS: This was a prospective, comparative, experimental animal study. After endometriotic implants were induced simultaneously, rats were divided into three groups. Group A was given 500 mg/kg of intravenous vitamin C every 2 days, starting immediately after implantation (n = 11). All rats had a second operation 21 days after the initial one and had the lesion volumes measured. Group B was given 500 mg/kg of intravenous vitamin C every 2 days, starting 21 days after this operation (n = 11). All rats were sacrificed 21 days after the third operation. Implant volume, weight measurements, and histopathological evaluation of the lesions were carried out. Group A received vitamin C throughout the study, while Group C (n = 11) was not given any medication. The findings in the three groups were compared. RESULTS: At the second laparotomy after the induction, Group A had the smallest implant volume with a statistically significant difference compared to Group B (p = 0.012). The end-of-study volumes of endometriotic implants of group B were significantly smaller than the first volumes (p < 0.05). CONCLUSION: Intravenous vitamin C treatment might have a suppressive effect on the prevention of endometriotic implant induction and regression of endometriotic implant volumes.

Update on menopausal hormone therapy.

PURPOSE OF REVIEW: Menopause management has undergone an eventful journey over the past decade; some dogmas got refuted, some new hypotheses took life, and the review is timely and relevant to the practice of clinical medicine in 2015. RECENT FINDINGS: The field stepped out of an era of absolutes into times of patient centeredness and an individualized perspective. SUMMARY: The onus now is to tailor management to address patient's needs while keeping in perspective individualized symptom burden and risks that may be unique to each aging woman.

The mRNA-binding protein HuR is regulated in the menstrual cycle and repressed in ectopic endometrium.

Cytokines modulate turnover of the endometrium during the menstrual cycle and contribute to the pathogenesis of endometriosis. Gene expression for cytokines is often regulated by proteins that bind to adenosine- and uridine-rich elements (AREs) in their transcripts to stabilize or destabilize bound messenger RNAs (mRNAs). HuR/ELAVL1 is an RNA-binding protein that stabilizes ARE-containing mRNAs. We hypothesized that HuR might play a role in regulating cytokine expression during the menstrual cycle and in endometriosis and characterized the expression and regulation of HuR in eutopic and ectopic human endometrium. Tissue sections obtained from normal (n = 23) and ectopic (n = 16) endometrium were immunostained for HuR, and staining intensity was evaluated by HSCORE. Cultured stromal cells isolated from normal endometrium were treated with vehicle, estradiol (E2), progesterone (P), E2 + P, tumor necrosis factor-α (TNF-α), and interleukin 1ß (IL-1ß) for 24 hours, and HuR expression was determined by Western blot. HuR immunoreactivity was significantly lower in the early proliferative and late secretory phases (157.5 ± 11.08 and 190.0 ± 15.2, respectively), compared to the mid-late proliferative (270.0 ± 8.0) and early-mid secretory phases (256.6 ± 20.2; P < .01, analysis of variance [ANOVA]). Furthermore, HuR expression was significantly lower in ectopic endometrial cells compared to normal endometrium in mid-late proliferative and early-mid-secretory phases (P < .01). Estrogen, P, or cytokines did not alter HuR expression in cultured endometrial stromal cells. Increased HuR levels in the mid-menstrual phases are likely to contribute to reduced mid-cycle cytokine expression and enhanced cellular survival in eutopic endometrium. In ectopic endometrium, elevated cytokine levels associated with endometriosis likely reduce HuR expression.