Therapeutic potential of acarbose in ameliorating the metabolic and endocrinological complications of polycystic ovarian syndrome: a review.

Polycystic ovarian syndrome is a perplexed condition addressing endocrinal, cardiometabolic and gynaecological issues. It affects women of adolescent age and is drastically increasing in the Indo-Asian ethnicity over the recent years. According to Rotterdam criteria, PCOS is characterized by clinical or biochemical excess androgen and polycystic ovarian morphology; however, it has been established in the recent years that PCOS exacerbates to further serious metabolic conditions on the long term. This is a narrative literature review and not systematic review and is based on PubMed searches with relevant keywords "Polycystic ovarian syndrome AND acarbose OR metformin OR myoinositol; PCOS AND metabolic syndrome OR cardiovascular disease OR menstrual irregularity OR infertility OR chronic anovulation OR clinical hyperandrogenism" used in the title and are limited to articles published in English language with no time limits. A prominent aspect of PCOS is hyperandrogenaemia and hyperinsulinemia. About 50-70% of afflicted women have compensatory hyperinsulinemia and close to one tierce suffer from anovulation and infertility. Insulin resistance leads to metabolic complications and works with luteinizing hormone in increasing the ovarian androgen production. This excess androgen leads to clinical manifestations, irregular menstrual cycles and infertility. There isn't an entire cure, only the symptomatic clinical factors are considered rather than focusing on the underlying long-term complications. Therefore, the article focuses on a potent alpha glucosidase inhibitor, acarbose which suppresses the post meal glucose and insulin by delaying the absorption of complex carbs. It exhibits cardio-metabolic and hormonal benefits and is well tolerable in the south asian population. This review highlights the safety, effectiveness of acarbose in ameliorating the long-term complications of PCOS.

A randomized interventional clinical trial assessing the safety and effectiveness of PeaNoc XL tablets in managing joint pain and inflammation in arthritis patients.

Background: Globally, alternative medicine is used widely by most patients for several health challenges. To evaluate the effectiveness and safety of PeaNoc XL Tablet in managing pain and inflammation, a randomized clinical trial and systematic study was designed. PeaNoc XL Tablet has been widely utilized for pain and inflammation management, but no previous studies have examined its efficacy and safety. The aim of this study was to determine the clinical effectiveness and safety profile of PeaNoc XL in patients with arthritis experiencing joint pain and inflammation. Methods: A randomized, controlled, and an open-label trial was conducted. A total of 155 patients (18 to 60 years) with arthritis were enrolled for participation. Using computer-generated random sequences, the study population was divided into two groups in a randomized manner. Group A received Standard therapy and Group B received Standard therapy with PeaNoc XL Tablet 400mg (two tablets OD after food). Results: Out of 155 patients, a total of 83 individuals were excluded from the study, leaving 72 patients who were randomly assigned to either Group A (n=36) or Group B (n=36). The administration of PeaNoc XL as an adjunct to standard therapy resulted in a significant reduction in levels of TNF-α (P<0.01), IL-1ß (P<0.001), IL-6 (P<0.01), and CRP (P<0.01) in arthritis patients experiencing joint pain and inflammation. Conversely, no notable differences were observed from the baseline in the standard therapy group. Conclusions: After 12 weeks of supplementation of PeaNoc XL tablets, as an add-on therapy helps in the reduction of pain score, joint stiffness, and physical stiffness. Trial registration:  CTRI/2022/10/046693.

Assessment of prescribing pattern and adverse drug reaction in patients receiving anticoagulant therapy: A prospective observational study.

Introduction: Cardiovascular diseases (CVD) are the leading cause of death worldwide as well as a major blockade to sustainable human development. It is among the leading causes of morbidity and mortality. Anticoagulants are among the most essential life-saving drugs that are generally used in cardiology for the prevention and treatment of many CVD. Objectives: To assess the prescribing pattern and adverse drug reaction (ADR) in patients receiving anticoagulant therapy for cardiac diseases. Methodology: This was a Prospective Observational study conducted in the Department of Cardiology, SRM Medical College Hospital and Research Center, Kattankulathur including 88 patients for 6 months. Results: Out of the 88 patients, the majority were males (73%) compared to females (27%), and the prevalence of CVD was found to be higher in patients above 40 years of age. Various categories of drugs prescribed to the patients were antiplatelets (14.88%), anticoagulants (8.79%), antianginal (13.82%), antihypertensives (15.7%), antihyperlipidemic (7.83%), thrombolytics (0.68%), Ionotropic agents (2.13%), antibiotics (5.31%), and other miscellaneous drugs (36.61%). The anticoagulant dosage regimens prescribed to the patients were categorized into monotherapy (9%), combinational therapy with antiplatelets (38%), and triple therapy (53%). The most commonly prescribed anticoagulant to the patients was Heparin (93.41%), followed by Warfarin (5.49%) and lastly Rivaroxaban (1.10%) respectively. From the details of the prescriptions analyzed, the average number of drugs per patient (prescription) was found to be 11.7. Conclusion: Heparin was found to be the most commonly used anticoagulant, Combination therapy of antiplatelets and antihypertensives was observed in most of the prescriptions, which is more effective than a single therapy. Polypharmacy was encountered in the study with an average number of 11.7 drugs per prescription. Several anticoagulant-related drug interactions were identified and there were two adverse drug reactions with Heparin. The prescribing pattern can be improved by reducing the number of drugs prescribed.

NK1 receptor antagonistic effect of 17-trifluoromethyl phenyl trinor prostaglandin F2α on the growth of human breast cancer cell line.

BACKGROUND: A growing number of genetic and cancer biology investigations have found that the tachykinin NK1 Receptor plays an important role in cancer cell proliferation and survival. In this study. The present study was designed to evaluate the inhibition of cell growth by 17-trifluoromethyl phenyl trinor prostaglandin F2α with NK1 receptor in breast cancer cell lines. MATERIALS AND METHODS: MDB-MB-468 and MCF-7 breast cancer cell lines were used in the experiment were blocked with PGF2a. Cell proliferation and apoptosis were analyzed to evaluate the cytotoxic effect. Cell cycle distribution, Caspase-3 enzyme activity, Bad and Bax protein expression through flow cytometry and molecular docking were carried out to analyze the NK1 receptor activity. RESULTS: We found that PGF2a has a high binding affinity towards NK1 Receptor from molecular docking studies. It exerted cytotoxic and antiproliferative effects against MDB-MB-468 and MCF-7 breast cancer cell lines. Our data found that treatment of cells with 17-TPGF2 resulted in cell death and showed that increased expression of Caspase-3, Bad, and Bax protein and further induces G2 cell cycle arrest. CONCLUSION: Overall this study investigates the NK1 receptor antagonistic effect of PGF2 against breast cancer cell lines. However, further studies are needed to better characterize the application of NK1 receptor inhibition in clinical cancer treatment and cytotoxicity effect.

Pro-inflammatory cytokine molecules from Boswellia serrate suppresses lipopolysaccharides induced inflammation demonstrated in an in-vivo zebrafish larval model.

BACKGROUND: Boswellia serrate is an ancient and highly valued ayurvedic herb. Its extracts have been used in medicine for centuries to treat a wide variety of chronic inflammatory diseases. However, the mechanism by which B. serrata hydro alcoholic extract inhibited pro-inflammatory cytokines in zebrafish (Danio rerio) larvae with LPS-induced inflammation remained unknown. METHODS: LC-MS analysis was used to investigate the extract's phytochemical components. To determine the toxicity of B. serrata extract, cytotoxicity and embryo toxicity tests were performed. The in-vivo zebrafish larvae model was used to evaluate the antioxidant and anti-inflammatory activity of B. serrata extract. RESULTS: According to an in silico study using molecular docking and ADMET, the compounds acetyl-11-keto-boswellic and 11-keto-beta-boswellic acid present in the extract had higher binding affinity for the inflammatory specific receptor, and it is predicted to be an orally active molecule. In both in-vitro L6 cells and in-vivo zebrafish larvae, 160 µg/mL concentration of extract caused a high rate of lethality. The extract was found to have a protective effect against LPS-induced inflammation at concentrations ranged between 10 and 80 µg/mL. In zebrafish larvae, 80 µg/mL of treatment significantly lowered the level of intracellular ROS, apoptosis, lipid peroxidation, and nitric oxide. Similarly, zebrafish larvae treated with B. serrata extract (80 µg/mL) showed an increased anti-inflammatory activity by lowering inflammatory specific gene expression (iNOS, TNF-α, COX-2, and IL-1). CONCLUSIONS: Overall, our findings suggest that B. serrata can act as a potent redox scavenger against LPS-induced inflammation in zebrafish larvae and an inhibitor of specific inflammatory genes.

Challenges of non-COVID-19 patients with chronic illness during the pandemic.

Challenges faced by non-COVID-19 patients with chronic illness are limitless during the lockdown period. These patients are mostly immunocompromised and vulnerable to infection. The worst affected would be chronic disease patients with lower household income. Patients' fear of approaching medical facilities and also travel restrictions limit the patients to reach the healthcare team, and either of this leads to poor health outcome. Frequent communication with chronic disease patients by healthcare professionals is a key to encourage the patients to be adherent to the medications and manage their disease conditions.

Dupilumab in the Treatment of Moderate to Severe Asthma: An Evidence-Based Review.

BACKGROUND: Asthma affects millions of patients across the globe and also accounts for numerous mortalities every year. The current pharmacologic approach to the treatment of asthma includes the use of glucocorticoids and beta-agonists mainly. However, these conventional therapies have poor controllability of moderate-to-severe asthma and also produce several side effects on their long-term use. These limitations had led to the development of biologics targeting the mediators involved in T helper 2-inflammation associated with the pathogenesis of asthma such as interleukin (IL) 4, IL-5, and IL-13. dupilumab, a fully human monoclonal antibody, an IL-4 receptor alpha-antagonist targeting IL-13 and IL-4 has a potential role in treatment of moderate-to-severe asthma and was approved by the Food and Drug Administration on October 19, 2018. The dual-antagonistic action of dupilumab on IL-4 and IL-13 receptors renders it more efficient in asthma treatment. OBJECTIVES: To review the efficacy and safety profile of dupilumab in the treatment of moderate-to-severe asthma. METHODS: Systematic search was performed via PubMed, Cochrane library, Embase, and ClinicalTrials.gov using the key words dupilumab, moderate-to-severe asthma, interleukin, IL-13, IL-4, and monoclonal antibody. Randomized controlled trials that compared between placebo and dupilumab in patients with uncontrolled asthma were included and observational studies were excluded in this review. RESULTS: The review of selected literature reveals that addition of dupilumab to conventional therapy improves forced expiratory volume in 1 second and reduces the risk of severe asthma exacerbations in patients. No significant differences in incidence of adverse drug reactions/adverse drug events were observed between dupilumab and placebo groups except higher rates of injection site reactions in the dupilumab group. CONCLUSIONS: Concomitant use of dupilumab with long-acting beta agonists used in combination with inhaled corticosteroids, improves clinical outcomes and quality of life in patients with moderate to severe asthma. Although dupilumab has a promising role in treatment of patients with asthma, it is still in the emerging stage for its acceptance globally. Ongoing studies will help to determine dupilumab's long-term efficacy and safety for its future extensive use.

Effect of Hemocare Syrup and Hemocare XT Tablets on Hemoglobin levels in iron deficiency anemia among women of reproductive age: A randomized, placebo controlled, open label trial.

BACKGROUND: Iron deficiency anemia is one of the important public health problems in developing countries among the women of reproductive age group. Hemocare formulation plays a significant role in Iron deficiency anemia because of its Iron content. The present study aimed to investigate the effect of Hemocare Syrup and Hemocare XT Tablets compared with placebo on Hemoglobin Levels in Iron Deficiency Anemia among Women of Reproductive Age. METHODS: A prospective, interventional, randomized, open label, placebo controlled trial has been conducted with 126 patients. Eligible patients randomly received either Placebo 100 mg or Hemocare XT Tablet 100 mg or 10 ml of Hemocare Syrup once daily in the same manner for 4 weeks. Hemoglobin values were documented at the end of 15th day, 21st day and 30th day. RESULTS: The baseline hemoglobin values were compared with each follow up and statistically significant difference was found at the end of 30th day of Hemocare Syrup and Hemocare XT treatment (P < 0.05) but there was no significant difference observed in the placebo group. The study results revealed that 30 days treatment of Hemocare Syrup and Hemocare XT Tablets increases the Hemoglobin levels to 12.46 ±â€¯0.44 g/dl and 12.90 ±â€¯0.98 g/dl from 9.08 ±â€¯2.54 g/dl and 9.68 ±â€¯2.04 g/dl respectively. CONCLUSION: Hemocare Syrup and Hemocare XT Tablets treatment showed clinically significant improvement in hemoglobin levels from the baseline and placebo group.

Safety, Efficacy, and Bioavailability of Fixed-Dose Combinations in Type 2 Diabetes Mellitus: A Systematic Updated Review.

PURPOSE: Type 2 diabetes mellitus (T2DM) is a multifactorial disease characterized by insulin resistance. As time progresses, monotherapy often does not provide effective glycemic control, generating the need for an add-on therapy. Hence, multiple oral hypoglycemic agents formulated as a single-dose form called fixed-dose combinations (FDCs) play an essential role in glycemic control. The purpose of this systematic review is to appraise the recently published evidence on the safety, efficacy, and bioavailability of FDCs. METHODS: A comprehensive literature search of PUBMED, Scopus, ScienceDirect.com, ProQuest, SpringerLink, clintrials.gov, Embase, and EBSCO using the key words FDCs, combination therapy, T2DM management, and add-on therapy was conducted. Studies on the safety profile/tolerability, efficacy, and bioavailability of various FDCs of oral hypoglycemic agents were preferred. FINDINGS: The systematic review of all the publications suggests that FDCs of oral hypoglycemic agents (OHAs) significantly reduce HbA1c and fasting plasma glucose values, thereby efficiently reducing hyperglycemia in patients in whom monotherapy fails. FDCs are the bioequivalent of the concomitant drugs administered as individual components. Improved adherence to FDCs and the absence of serious adverse drug reactions compared with dual therapy play an important role in decreasing the incidence of hyperglycemia in patients with T2DM. IMPLICATIONS: From this updated review, it was found that metformin was the most widely used component of FDCs with other OHAs. Studies on the safety and efficacy of newly approved OHAs such as sodium glucose cotransporter inhibitors were limited. An increasing number of randomized trials on the safety and efficacy of newly emerging FDCs suggests that they would be better treatment options for T2DM patients.

Comparative assessment of methylcobalamin and ascorbic acid on cognitive function in post-menopausal women - A randomized, double-blind trial.

INTRODUCTION: A decline in cognitive function occurs as women progress through the menopausal transition. OBJECTIVE: The present study was designed to compare the effect of Methylcobalamin and Ascorbic Acid on Cognitive Function in post-menopausal women. METHODS: A randomized, double-blind trial was conducted in postmenopausal women with mild to moderate cognitive dysfunction. Eligible 56 subjects were randomized, the effect of ascorbic acid (500 mg OD) and methylcobalamin (50 mcg OD) was compared after 12 weeks of treatment. MMSE Questionnaire was used to assess the cognitive function, and ß-amyloid42 was estimated in serum by enzyme-linked immunosorbent assay (ELISA). RESULTS: In MMSE score, delayed verbal recall (P = 0.027), naming (P = 0.042) and repetition (P = 0.031) scores were significantly improved in ascorbic acid group when compared to baseline. The ß-amyloid42 level was decreased significantly in subjects receiving ascorbic acid (P = 0.04) when compared to Methylcobalamin group (P = 0.31). The inverse relationship between ß-amyloid42 levels and the MMSE score was found in ascorbic acid treatment (r = 0.6324, P = 0.0004). CONCLUSION: Based on MMSE and ß-amyloid42 results, ascorbic acid showed improvement in cognitive function among post-menopausal women when compared to methylcobalamin supplement.

Comparative inhibitory potential of selected dietary bioactive polyphenols, phytosterols on CYP3A4 and CYP2D6 with fluorometric high-throughput screening.

Cytochrome P450 (CYP450) inhibition by the bioactive molecules of dietary supplements or herbal products leading to greater potential for toxicity of co-administered drugs. The present study was aimed to compare the inhibitory potential of selected common dietary bioactive molecules (Gallic acid, Ellagic acid, ß-Sitosterol, Stigmasterol, Quercetin and Rutin) on CYP3A4 and CYP2D6 to assess safety through its inhibitory potency and to predict interaction potential with co-administered drugs. CYP450-CO complex assay was carried out for all the selected dietary bioactive molecules in isolated rat microsomes. CYP450 concentration of the rat liver microsome was found to be 0.474 nmol/mg protein, quercetin in DMSO has shown maximum inhibition on CYP450 (51.02 ± 1.24 %) but less when compared with positive control (79.02 ± 1.61 %). In high throughput fluorometric assay, IC50 value of quercetin (49.08 ± 1.02-54.36 ± 0.85 µg/ml) and gallic acid (78.46 ± 1.32-83.84 ± 1.06 µg/ml) was lower than other bioactive compounds on CYP3A4 and CYP2D6 respectively but it was higher than positive controls (06.28 ± 1.76-07.74 ± 1.32 µg/ml). In comparison of in vitro inhibitory potential on CYP3A4 and CYP2D6, consumption of food or herbal or dietary supplements containing quercetin and gallic acid without any limitation should be carefully considered when narrow therapeutic drugs are administered together.

Novel drug targets in clinical development for heart failure.

BACKGROUND: Heart Failure continues to be a leading cause of mortality and morbidity worldwide. The dismal prognosis of patients in acute heart failure (AHF) can be altered only by exploring novel drug molecules. Although the treatment for chronic heart failure (CHF) has seen remarkable progress, there is still a need to develop molecules that could improve the long-term survival outcomes. PURPOSE: To review the drug targets for acute and chronic heart failure and the molecules acting on these targets. METHODS: The article discusses on the mechanism of how the potential drug targets can be modulated to alter the pathophysiological processes in heart failure. Current evidence on molecules acting on these targets has also been described from published literature using the PubMed and Clinical Trials.gov databases. RESULTS: Some of the molecules that are currently being explored for AHF includeomecamtiv mecarbil which activates cardiac myosin ATPase, istaroxime an ionotropicagent that activates SERCA2a pump activity, ularitide and carperitide which are ANP(atrial natriuretic peptide) analogues and recombinant relaxin. Some of the targets forCHF include stabilization of ryanodine receptors, renin inhibition, neprilysin inhibition, neuregulins and SERCA2a gene therapy. CONCLUSION: Clinical trials in heart failure must be designed to minimize the risk of "drug failures." Nevertheless, it is hoped that in the days to come, drugs with superior efficacy and safety will eventually be produced from the surge of molecules that are in the pipeline.

Assessment of serum leptin and resistin levels in association with the metabolic risk factors of pre- and post-menopausal rural women in South India.

OBJECTIVES: Menopausal status is related with weight gain, abnormal lipid and glucose metabolism leading to metabolic syndrome susceptibility. The aim of this study is to determine circulating serum leptin and resistin levels and to correlate these levels in relationship with the metabolic factors in pre- and post-menopausal women. METHODS: A cross-sectional study has been carried out for 34 subjects who were in post-menopause and 31 subjects who had regular menstruation in south Indian rural women. Anthropometric indices, blood pressure, fasting blood sugar (FBS), fasting lipid profile, fasting leptin and resistin levels were measured. RESULTS: In a total of 65 subjects, the mean age of pre-menopausal group was 38.65±6.21 and that of post-menopausal group was 55.32±6.32. Fasting serum leptin level was increased considerably in post-menopausal women when compared to pre-menopausal women (P=0.018). Resistin has no significant relationship with metabolic factors except Body Mass Index (BMI) in both the groups. Triglycerides and FBS were lower in pre-menopausal group when compared to post-menopausal group (P<0.001). Leptin was well correlated with BMI in pre-menopausal women (r(2)=0.7120, P<0.0001) as well as post-menopausal women (r(2)=0.2470, P=0.0028). Leptin also had significant correlation with FBS in both pre (r(2)=0.1373, P=0.0402) and post-menopausal women (r(2)=0.2141, P=0.0401). Systolic blood pressure was positively associated with the leptin levels in post-menopausal women (P<0.001). CONCLUSION: Leptin was found to have significant association with metabolic factors when compared to resistin in pre- and post-menopausal women and there is no doubt that association of BMI and FBS elevates the level of leptin in both the category.