Impact of antioxidants in improving semen parameters like count, motility and DNA fragmentation in sub-fertile males: a randomized, double-blind, placebo-controlled clinical trial.

Male infertility is solely responsible for 20-30% of infertility cases. Oxidative damage of sperm DNA is positively linked with oligoasthenoteratozoospermia (OAT), and male infertility. The antioxidants are being explored worldwide to combat OAT, sperm DNA fragmentation and reactive oxygen species. The objective of the study was to assess the effectiveness of an antioxidant blend in improving sperm count, semen parameters and reducing DNA fragmentation index (DFI) in sub-fertile males. A prospective, double-blind, randomized, placebo-controlled trial was conducted in 300 sub-fertile males (25-45 years) from ten study sites in India. Subjects were randomized in either the antioxidant blend treatment group or placebo group. We assessed changes in sperm count, motility, normal morphology, semen volume, and percent DFI before and after treatment (90 days). To further stratify data on different criteria post hoc analysis was performed. Statistical analysis was performed using SPSS 10.0 software. There were improvements in sperm count, semen volume, sperm motility, and sperm normal morphology in the treatment group. There was improvement in sperm count in severe oligospermia subjects (sperm count < 5 million/mL, 5-10 million/mL, 10.1-15 million/mL), and high-extremely higher baseline DFI (20-30%, 31-40% and above 40%), as per post hoc analysis. There was no premature discontinuation and adverse events were reported during the study, indicating safety and well-tolerability of treatment. Study results confirmed the well-researched fact of antioxidants being effective to reduce oxidative stress and thus improve sperm DNA integrity and also improved semen parameters in males aged 40 and above. Trial Registration: Clinical Trials Registry-India Identifier: CTRI/2020/12/029590.

Modified tamarind kernel polysaccharide-based matrix alters neuro-keratinocyte cross-talk and serves as a suitable scaffold for skin tissue engineering.

Advanced technologies like skin tissue engineering are requisite of various disorders where artificially synthesized materials need to be used as a scaffold in vivo, which in turn can allow the formation of functional skin and epidermal layer with all biological sensory functions. In this work, we present a set of hydrogels which have been synthesized by the method utilizing radical polymerization of a natural polymer extracted from kernel of Tamarindus indica, commonly known as Tamarind Kernel Powder (TKP) modified by utilizing the monomer acrylic acid (AA) in different mole ratios. These materials are termed as TKP: AA hydrogels and characterized by Atomic Force Microscopy (AFM), surface charge, and particle size distribution using Dynamic Light Scattering measurements. These materials are biocompatible with mouse dermal fibroblasts (NIH- 3T3) and human skin keratinocytes (HaCaT), as confirmed by MTT and biocompatibility assays. These TKP: AA hydrogels do not induce unwanted ROS signaling as confirmed by mitochondrial functionality determined by DCFDA staining, Mitosox imaging, and measuring the ATP levels. We demonstrate that in the co-culture system, TKP: AA allows the establishment of proper neuro-keratinocyte contact formation, suggesting that this hydrogel can be suitable for developing skin with sensory functions. Skin corrosion analysis on SD rats confirms that TKP: AA is appropriate for in vivo applications as well. This is further confirmed by in vivo compatibility and toxicity studies, including hemocompatibility and histopathology of liver and kidney upon direct introduction of hydrogel into the body. We propose that TKP: AA (1: 5) offers a suitable surface for skin tissue engineering with sensory functions applicable in vitro, in vivo, and ex vivo. These findings may have broad biomedical and clinical importance.

Unscheduled bleeding in combined oral contraceptive users: focus on extended-cycle and continuous-use regimens.

Combined oral contraceptives (COCs) are highly effective when correctly used but unscheduled bleeding, which occurs fairly commonly during the early months, is disruptive for many women. The mechanisms underlying this bleeding are not fully understood. Several studies have shown that extended-cycle or continuous-use COCs are typically associated with higher initial rates of unscheduled bleeding than are conventional 21-day cyclical COCs. Some medicines, herbal supplements and smoking may increase unscheduled bleeding by interfering with estrogen metabolism. The most common cause of unscheduled bleeding is non-adherence to a prescribed COC regimen. Compliance can be improved by appropriate counselling of women about the possibility of unscheduled bleeding and the importance of adherence to the pill regimen. If abnormal bleeding persists beyond 3-4 months and causes such as incorrect usage can be ruled out, other causes should be considered.

Abnormal uterine bleeding: a focus on polycystic ovary syndrome.

Abnormal uterine bleeding imposes major medical, social and financial problems for women, their families and the health services. Abnormal uterine bleeding refers to the regularity, frequency, duration and volume of bleeding. Irregular menstrual bleeding is most common at the extremes of reproductive life, in the initial 12-18 months after menarche and 5-6 years before the menopause begins. In Australia, the estimated cost of investigating and managing heavy menstrual bleeding alone is approximately AUS $6 million per annum. This article addresses the common causes of irregular bleeding in pre- and peri-menopausal women and presents an investigational approach.

Bleeding with menopausal hormone therapy.

Hormone therapy is highly effective for the treatment of menopausal vasomotor symptoms and vaginal dryness, but commonly leads to unscheduled vaginal bleeding and spotting. This frequently leads to invasive investigations to exclude underlying malignancy and is also very unpopular amongst users. In most cases, no pathology is found and the mechanisms underlying this irregular bleeding are poorly understood. Relatively few studies have investigated how combined hormone therapy might cause endometrial breakdown and bleeding. Evidence to date suggests that hormone therapy exposure induces changes in the density, distribution and structure of endometrial vessels, as well as alterations in the stroma, potentially leading to increased production of vasoactive mediators. The mechanisms of bleeding with menopausal hormone therapy seem to differ from those seen during normal menstruation and breakthrough bleeding in users of long-acting progestogen-only contraception.