A review of metabolic and microbial influences on women with polycystic ovarian syndrome.

INTRODUCTION: Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine and metabolic disorder affecting reproductive-aged women worldwide. Characterized by irregular menstruation, signs of hyperandrogenism, polycystic ovaries via ultrasound ovarian dysfunction. AREA COVERED: The review delves into the intricate pathophysiological mechanisms underlying the syndrome. Dysregulation of the hypothalamic-pituitary-ovarian axis, IR, obesity, and hyperandrogenism contribute to anovulation and follicular dysfunction which is associated with gut dysbiosis, bile metabolites, and an unhealthy diet. Metabolomics and genomics analyses offer insights into the metabolism of bile acids (BAs) and gut microbiota dysbiosis in PCOS. BAs, crucial for metabolic regulation, are influenced by microbes, impacting hormonal balance. Disruptions in gut microbiota contribute to hormonal dysregulation. Interconnected pathways involving BAs and gut microbiota are pivotal in PCOS. Therapeutic implications include a healthy diet, exercise, and interventions targeting gut microbiota modulation and BAs metabolite to alleviate PCOS symptoms and improve metabolic health. CONCLUSION: PCOS requires a multifaceted, multidisciplinary approach for effective management, including lifestyle changes, medications, and emerging therapies. Tailored strategies considering individual needs and personalized treatment plans are crucial for successful PCOS management. Despite existing knowledge, comprehensive investigations are needed to bridge research gaps and discern the interconnected pathways linking the development of PCOS and the gut-bile axis which are interconnected with metabolic disorders and the development of PCOS. Gut microbiota and hormonal regulation offer promising avenues for innovative therapeutic strategies aimed at addressing the root causes of PCOS and improving patient outcomes.

Unravelling the oxygen factor - An investigation of transcriptional activation of hypoxia associated placental angiogenesis in recurrent pregnancy loss (RPL) patients from Assam, India.

INTRODUCTION: Recurrent pregnancy loss (RPL) is defined as the spontaneous loss of two or more consecutive pregnancies before 20 weeks of gestation, and affects 7.46 % of the Indian population. About 40-50 % of RPL cases are idiopathic making it a therapeutic challenge for clinicians. This study focuses on elucidating the role of hypoxia-associated placental angiogenesis in these idiopathic RPL cases. METHODS: Whole blood and product of conception (POCs) were collected from RPL patients (N = 87) and cases of voluntary abortions (medically terminated pregnancy, MTP; n = 110) as controls with informed consent. Serum separated from whole blood was used to study the ROS-antioxidant status in the cases and controls through colorimetric assays and ELISA. The mRNA extracted from placental tissue samples were used to determine the hypoxic and angiogenic status in cases and controls through real time PCR. Statistical analysis was also carried out to correlate the differential hypoxic status between RPL and MTP cohorts with the expression of angiogenic factors (VEGFA, VEGFR1 and VEGFR2). RESULTS: HIF1α mRNA expression was found to be upregulated in the RPL cases. While the serum levels of H2O2 (p = 0.012), guanine oxides and lipid hydroperoxides (LPO) were increased in the RPL cases, reduced glutathione (GSH) was found to be significantly decreased (p = 0.012). Additionally, AUROC analysis also shows an excellent discriminatory ability of 0.850 for serum H2O2 levels. VEGF-A and VEGF-R1 mRNA expression was also found to be downregulated in the RPL cases compared to MTP. DISCUSSION: This study indicates that increased oxidative stress may lead to aberrations in the VEGF pathway resulting in improper placentation in RPL cases, and subsequently, pregnancy loss.

Influence of Temperature and Humidity on Pregnancy Rate of Murrah Buffaloes under Subtropical Climate.

Heat stress has adverse effects on fertility of dairy animals. Decline in fertility is linearly associated with an increase in combination of both temperature and humidity. The purpose of this study was to investigate the relationship between temperature humidity index (THI) and the pregnancy rate of Murrah buffaloes in a subtropical climate. The effects of genetic and non-genetic factors viz., sire, parity, period of calving and age group at first calving were found non-significant on pregnancy rate. The effect of THI was found significant (p<0.001) on pregnancy rate of Murrah buffaloes calved for first time and overall pregnancy rate. The threshold THI affecting the pregnancy rate was identified as THI 75. The months from October to March showed THI<75 and considered as non heat stress zone (NHSZ), while months from April to September were determined as heat stress zone (HSZ) with THI≥75. The lowest overall pregnancy rate (0.25) was obtained in July with THI 80.9, while the highest overall pregnancy rate (0.59) was found in November with THI 66.1. May and June were identified as critical heat stress zone (CHSZ) within the HSZ with maximum decline (-7%) in pregnancy rate with per unit increase in THI. The highest overall pregnancy rate was estimated as 0.45 in NHSZ with THI value 56.7 to 73.2. The pregnancy rate was found to have declined to 0.28 in HSZ with THI 73.5 to 83.7. However, the lowest pregnancy rate was estimated as 0.27 in CHSZ with THI value 80.3 to 81.6.

Forced Degradation Behaviour of Fluphenazine Hydrochloride by LC and Characterization of its Oxidative Degradation Product by LC-MS/MS.

A novel, stability-indicating high-performance liquid chromatographic (HPLC) method is delivered for the determination of fluphenazine hydrochloride (FPZ) and its degradation products. The forced degradation testing of FPZ was carried out for hydrolytic, oxidative, photolytic, and thermal degradation. The degradation appeared using a reversed-phase C18 column at ambient temperature with a mobile phase comprised of methanol : acetonitrile : (10 mM) ammonium acetate (70:15:15, v/v/v) pH 6.0, adjusted with acetic acid, having a flow rate of 1 ml min(-1) and a detection wavelength at 259 nm. Primarily, the maximum degradation products were formed under oxidative stress conditions. The product was distinguished through LC-MS/MS fragmentation studies. Based on the results, a more complete degradation pathway for the drug could be proposed. The modernized method was found to be precise, accurate, specific, and selective. The method was found to be suitable for the quality control of fluphenazine hydrochloride in the tablet as well as in stability-indicating studies.

Auditory brainstem evoked responses in hyperlipidaemia: effect of various lipid fractions on auditory function.

OBJECTIVE: To evaluate the effect of different lipid fractions on auditory brainstem evoked responses in hyperlipidaemia. METHOD: We conducted a single institution (medical college), prospective, cross-sectional study of 25 hyperlipidaemic patients and 25 normolipidaemic controls, all with a normal hearing threshold on pure tone audiometry. Brainstem evoked response audiometry results were recorded in both groups. The hyperlipidaemic group were further divided into two subgroups, based on the serum value of each lipid fraction: those with less than and those with greater than the mean serum value. These two subgroups were further compared with the control group. RESULTS: The hyperlipidaemic and normolipidaemic groups had statistically significant differences for all audiometry waves apart from the wave I and the III-V interpeak latencies. The subgroups had a statistically significant difference in brainstem evoked responses. We found a statistically significant association between low-density lipoproteins and many waveforms in the hyperlipidaemic group. CONCLUSION: We found that low-density lipoproteins were significantly associated with many waveforms in hyperlipidaemic patients. Thus, low-density lipoproteins may be important in auditory dysfunction.

Design and evaluation of biodegradable, biosensitive in situ gelling system for pulsatile delivery of insulin.

Biodegradable glucose-sensitive in situ gelling system based on chitosan for pulsatile delivery of insulin was developed. The sols/gels were thoroughly characterized for swelling properties, rheology, texture analysis and water content. The developed glucose-sensitive gels responded to varied glucose concentrations in vitro indicating their ability to function as environment-sensitive systems. Insulin load onto the gels was optimized and was found to affect the rheological behavior of these gels, the final preparation used for in vitro contained 1IU/200mul of the sol. These gels released the entrapped insulin in a pulsatile manner in response to the glucose concentration in vitro. Furthermore, the formulations when evaluated for their in vivo efficacy in streptozotocin-induced diabetic rats at a dose of 3IU/kg, demonstrated their ability to release insulin in response to glucose concentration and were preferred much better against subcutaneously given plain insulin formulation used as the control. Together, these preliminary results indicate that biosensitive chitosan in situ gelling systems have substantial potential as pulsatile delivery systems for insulin.

Hydrogels for pharmaceutical and biomedical applications.

Hydrogels are crosslinked hydrophilic polymer structures that can imbibe large amounts of water or biological fluids. Hydrogels are one of the upcoming classes of polymer-based systems that embrace numerous biomedical and pharmaceutical applications. This review discusses various parameters of hydrogels such as surface properties, water content and swelling behavior, effect of nature of polymer, ionic content, and thermodynamics, all of which can influence the biomedical usage of hydrogels. Meanwhile, intelligent or environment-sensitive hydrogels and bioadhesive hydrogels continue to be important materials for medical applications; therefore, a part of this review is devoted to some of their important classes. Hydrogels are extensively used for various biomedical applications--tissue engineering, molecular imprinting, wound dressings materials, immunoisolation, drug delivery, etc. Thus, this review aims to throw light on the numerous applications that hydrogels have in the biomedical arena.