Effectiveness of dual combination therapy of acarbose plus metformin and acarbose plus myo-inositol in ameliorating the metabolic and endocrinologic complications of polycystic ovary syndrome - A randomized controlled trial.

INTRODUCTION: PCOS, beyond being characterized by reproductive disturbances, is a complicated rapid expanding metabolic and endocrinologic disorder of the recent times. Nearly 70% PCOS women show resistance to insulin. AIM: The aim of the study is to determine and compare the effectiveness of acarbose plus metformin and acarbose plus myo-inositol combination therapy in alleviating the metabolic and endocrinologic complications of PCOS. MATERIALS AND METHODS: An open labelled RCT was conducted on 168 PCOS women attending the gynaecology clinic at SRM MCH & RC, Chengalpattu and the trial was registered in CTRI (No. CTRI/2022/04/041877). Group A (n = 56) received metformin 500 mg/TID alone; group B (n = 54) received (acarbose 25 mg/TID for 4 weeks then 50 mg/TID for other 20 weeks) along with metformin 500 mg/TID and group C (n = 54) received (acarbose 25 mg/TID for 4 weeks then 50 mg/TID for other 20 weeks) along with myoinositol 1000 mg/BD. All parameters were measured at baseline and at the end of 6 months. RESULTS: Significant reduction of LH, LH: FSH, TT, HOMA-IR was observed in all the groups. FSH increased only in metformin group. Increase in serum progesterone and reduction in FI, TGL, LDL were significant only in acarbose plus myo-inositol group. SHBG and HDL increased significantly only in acarbose plus metformin group. No changes in BMI, TC and VLDL were observed in any group. CONCLUSION: Therefore, decrease in FI, HOMA-IR, TGL, LDL seen in acarbose plus myo-inositol group indirectly contributes to cardio-metabolic safety in PCOS. Similarly, a significant increase in SHBG levels with acarbose plus metformin group shows correction of the excess androgen and restoration of ovulation.

Effect of L-Carnosine in Patients with Age-Related Diseases: A Systematic Review and Meta-Analysis.

INTRODUCTION: L-carnosine has been found to have multimodal activity. AIM: The aim of this review was to find out the efficacy of L-carnosine in patients with age-related diseases. METHODS: Clinical studies evaluated the effect of L-carnosine on cancer, cardiovascular disease, diabetes, and neurodegenerative disorders were searched in electronic bibliographic databases. The protocol has been registered with PROSPERO (CRD42022314033). The revised Cochrane risk of bias tool for randomized trials was used to assess all of the reports for risk of bias. RevMan 5.4 was used to conduct the meta-analysis. RESULTS: Following the screening process, 14 papers were selected for systematic review, with 9 of them being qualified for meta-analysis. Many of the included studies showed that L-carnosine has potential therapeutic activity in age related diseases. Results from the meta-analysis showed that in diabetes mellitus, HbA1c [mean difference (MD) 95% CI = -1.25 (-2.49, -0.022); p = 0.05; p = 0.001; I2 = 85%] and fasting blood sugar (FBS) [MD 95% CI = -12.44 (-22.44, -2.44); p = 0.01; p = 0.40; I2 = 0%] and in neurodegenerative disorder, Wechsler Memory Scale Logical Memory 2 (WMS-LM2) [MD 95% CI = 1.34 (0.83, 1.85); p < 0.00001; p = 0.43; I2 = 0%], showed statistically significant difference, favoring the L-carnosine group over the control group. While in neurodegenerative disorder, Alzheimer 's Disease Assessment Scale (ADAS) [MD 95% CI = 0.98 (-1.55, -0.42); p = 0.0007; p = 0.86; I2 = 0%] and Back Depression Inventory (BDI) [MD 95% CI = -1.12 (-1.87, -0.37); p = 0.003; p = 0.73; I2 = 0%] showed statistically significant difference, favoring the control group over L-carnosine group. CONCLUSIONS: Clinical studies were conducted to manage chemotherapy induced toxicities and there are no clinical studies available for its anti-cancer use, and the current evidence does not support its use in the treatment of cardiovascular disease.

Level of adherence to anti-tubercular treatment among drug-sensitive tuberculosis patients on a newly introduced daily dose regimen in South India: A cross-sectional study.

INTRODUCTION: Tuberculosis (TB) patients on the National Tuberculosis Elimination Program (NTEP) treatment protocol receive daily doses without health professional-supervised drug intake as during the previous directly observed treatment short-course (DOTS) regimen. We aimed to measure the level of adherence to anti-tubercular treatment (ATT) and the reasons for non-adherence among drug-sensitive TB patients on a daily-dose regimen in South India. METHODS: A cross-sectional study was conducted among TB patients who received ATT as part of the standard treatment protocol in NTEP. Patients were interviewed to capture their understanding of TB, adherence, and the reason for non-adherence to ATT using validated instruments. Urine drug metabolite testing was performed using the high-performance liquid chromatography (HPLC) technique to confirm adherence. RESULTS: A total of 488 patients were recruited for the study. 64.8% of patients had 'good knowledge' about TB and ATT. According to the subjective report, 63.7% of patients were adherent, but urine drug metabolite testing revealed 53.4% adherence. A statistically significant difference (p < 0.05) exists between subjective and objective adherence measures. Patient-reported reasons for non-adherence were side effects of ATT (18.6%), loss of daily wages (15.0%), and forgetfulness (10.0%), among others. CONCLUSIONS: Nearly half of the patients were non-adherent to the daily dosing regimen. Adherence as reported by the patients is unreliable, and urine testing could be used in routine care to assess adherence. CLINICAL TRIAL REGISTRATION AND NUMBER: CTRI/2020/04/024941.

Functional and Structural Impact of Deleterious Missense Single Nucleotide Polymorphisms in the NR3C1, CYP3A5, and TNF-α Genes: An In Silico Analysis.

Human diseases are generally influenced by SNPs (single nucleotide polymorphisms). The mutations in amino acid residues generated by deleterious SNPs contribute to the structural and functional diversity of the encoded protein. Tumor necrosis factor-α (TNF-α), Glucocorticoid receptor gene (NR3C1), and Cytochrome P450 3A5 (CYP3A5) play a key role in glucocorticoid resistance susceptibility in humans. Possible causative mutations could be used as therapeutic targets and diagnostic markers for glucocorticoid resistance. This study evaluated the missense SNPs of TNF-α, NR3C1, and CYP3A5 to predict their impact on amino acid changes, protein interaction, and functional stability. The protein sequence of dbSNP was obtained and used online in silico method to screen deleterious mutants for the in silico analysis. In the coding regions of TNF-α, NR3C1, and CYP3A5, 14 deleterious mutations were discovered. The protein functional and stability changes in the amino acid between native and mutant energy were identified by analyzing the changes in the hydrogen bonding of these mutants from native, which were all measured using Swiss PDB and PyMOL. F446S and R439K had the highest root-mean-square deviation (RMSD) values among the 14 deleterious mutants. Additionally, the conserved region of amino acid protein interaction was analyzed. This study could aid in the discovery of new detrimental mutations in TNF-α, NR3C1, and CYP3A5, as well as the development of long-term therapy for corticosteroid resistance in several inflammatory diseases. However, more research into the deleterious mutations of the TNF-α, NR3C1, and CYP3A5 genes is needed to determine their role in corticosteroid resistance.

Phenytoin induced Stevens-Johnson Syndrome-toxic Epidermal Necrolysis Overlap Exacerbated by Cephalexin in a 65-Year-old Neurosurgical Patient: A Rare Case Report.

OBJECTIVE: To report a rare case of drug induced overlap of Stevens-Johnson syndrome and Toxic Epidermal Necrosis Syndrome exacerbated by cephalexin. CASE PRESENTATION: In this case report, we present a 65-year-old female who had come to the hospital with complaints of Sloughing of the skin and redness all over the body with raised body temperature. She was on therapeutic Phenytoin to prevent the post-surgical complications of Communicating Hydrocephalus. After a detailed examination, it was found that the patient had misemployed with an overdose of Phenytoin. The patient was found with nikolsky sign and diagnosed as Stevens- Johnson syndrome and Toxic Epidermal Necrosis overlap. This case report emphasizes phenytoin induced Stevens-Johnson syndrome and Toxic Epidermal Necrosis syndrome exacerbated by cephalexin. CONCLUSION: By witnessing this phenomenon, we could figure out the association between cephalexin and Stevens-Johnson syndrome- Toxic Epidermal Necrosis syndrome overlap. The Immediate dismissal of the offending agent and commencement of supportive care was found to be effective.