Evaluating the Efficacy, Safety, and Tolerability of Combination Therapy of Dapagliflozin and Linagliptin Over Dapagliflozin and Vildagliptin in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin.

Background Type 2 diabetes mellitus (T2DM) patients commonly undergo metformin monotherapy. This study aims to compare the efficacy, safety, and tolerability of combination therapy of dapagliflozin plus linagliptin versus dapagliflozin plus vildagliptin as add-on therapy in T2DM patients inadequately controlled on metformin. Methodology This was an 18-week, multicenter, randomized, double-blind, active-controlled, parallel-group, phase III clinical study. About 236 participants were randomly assigned to receive either a fixed-dose combination of dapagliflozin 10 mg plus linagliptin 5 mg tablets or a fixed-dose combination of dapagliflozin 10 mg plus vildagliptin SR 100 mg tablets added to metformin monotherapy. The primary outcome was the mean change in hemoglobin A1c (HbA1c) from baseline to the end of week 16. The key secondary endpoints were mean change in postprandial blood glucose (PPBG), fasting blood glucose (FBG), body weight, and the proportion of participants achieving HbA1c less than 7.0%. Results The dapagliflozin/linagliptin combination therapy showed a more significant change in HbA1c from baseline to the end of 16 weeks (mean reduction: -1.59% vs. -1.25%) compared to dapagliflozin/vildagliptin (p < 0.0001). Additionally, compared to the dapagliflozin/vildagliptin group, the dapagliflozin/linagliptin group demonstrated a significant reduction in both PPBG (mean reduction: -59.99 mg/dL vs. -55.34 mg/dL) and FPG (mean reduction: -32.91 mg/dL vs. -26.78 mg/dL). A total of 18 adverse events were reported in 17 (7.20%) participants, all of which were mild and resolved completely. There were no serious adverse events. Conclusions Compared to dapagliflozin and vildagliptin combination therapy, dapagliflozin and linagliptin fixed-dose combination provided clinically significant improvements in glycemic control. Because of its effectiveness, safety, and tolerability, the fixed-dose combination of dapagliflozin and linagliptin was a better option for treating T2DM patients who had previously only received metformin monotherapy.

Effect of Vaccination on COVID-19 Severity and Outcome: A Comparative Study in a Tertiary Care Hospital.

INTRODUCTION: Vaccination is an important aspect of preventing/decreasing the severity of any viral disease including severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). This disease being very new in the experience of mankind has very little data on the effect of vaccination on the severity of this disease. We conducted this study with the primary objective to assess the severity and clinical outcome of COVID-19 infections among nonvaccinated and vaccinated individuals. MATERIALS AND METHODS: This was a hospital-based retrospective cohort study including all individuals developing microbiologically confirmed COVID-19 over 5 months from February to 31st July 2021. A questionnaire was used to acquire demographic details, history of vaccination with dates, severity of COVID-19 infection, comorbidities, and outcome. Patients found positive microbiologically for SARS-CoV-2 before any dose of its vaccine were considered nonvaccinated, while patients developing SARS-CoV-2 infection even after a single dose or both doses of vaccine were considered "vaccinated." The outcome and mortality among the vaccinated and nonvaccinated patients were evaluated and compared. RESULTS: The study included 2,879 patients, but complete data were obtained only from 1,500 patients. A total of 1,500 patients were analyzed, out of which 880 are male and 620 are female. The severity of the disease was categorized into mild, moderate, and severe in the age-group of <60 years and >60 years with urban (1051, 70.07%) and rural (449, 29.93%) populations. A total number of recovered patients (n = 245), died patients (n = 215) in the age-group of >60 years while the total recovered patients (n = 823) and dead patients (n = 217) in the age-group <60 years with p = 0.001. Total vaccinated patients in the age-group >60 years (n = 204) and not vaccinated (n = 256) while in the age-group of <60 years total vaccinated n = 229 and not vaccinated n = 811. The outcome of disease in the age-group of >60 years in nonvaccinated 50% recovered and 50% died during the course of illness while in the vaccinated 57.3% recoverd and 42% died p-value 0.14, while in the age-group of <60 years recovery in nonvaccinated 77.6% and death in nonvaccinated was 27.32% while in vaccinated patients 82.28% were recovered and 15% died with significant p-value 0.04. Disease outcome was not found significantly associated with a number of doses with p-values of 0.84 and 0.507 in the age-group of >60 years and <60 years, respectively. A total number of 56 patients received Covaxin and 377 patients received Covishield and disease outcome was not found significantly associated with the type of vaccine. CONCLUSION: Vaccination against COVID-19 was significantly effective in terms of hospitalization and disease severity. Vaccinated persons were less among patients with COVID-19 hospitalization and with severe disease progressing to death. These findings indicate vaccination is helpful in reducing the development of severe COVID-19 infection as compared to nonvaccinated status.

Homology Modelling, Molecular Docking and Molecular Dynamics Simulation Studies of CALMH1 against Secondary Metabolites of Bauhinia variegata to Treat Alzheimer's Disease.

Calcium homeostasis modulator 1 (CALHM1) is a protein responsible for causing Alzheimer's disease. In the absence of an experimentally designed protein molecule, homology modelling was performed. Through homology modelling, different CALHM1 models were generated and validated through Rampage. To carry out further in silico studies, through molecular docking and molecular dynamics simulation experiments, various flavonoids and alkaloids from Bauhinia variegata were utilised as inhibitors to target the protein (CALHM1). The sequence of CALHM1 was retrieved from UniProt and the secondary structure prediction of CALHM1 was done through CFSSP, GOR4, and SOPMA methods. The structure was identified through LOMETS, MUSTER, and MODELLER and finally, the structures were validated through Rampage. Bauhinia variegata plant was used to check the interaction of alkaloids and flavonoids against CALHM1. The protein and protein-ligand complex were also validated through molecular dynamics simulations studies. The model generated through MODELLER software with 6VAM A was used because this model predicted the best results in the Ramachandran plot. Further molecular docking was performed, quercetin was found to be the most appropriate candidate for the protein molecule with the minimum binding energy of -12.45 kcal/mol and their ADME properties were analysed through Molsoft and Molinspiration. Molecular dynamics simulations showed that CALHM1 and CALHM1-quercetin complex became stable at 2500 ps. It may be seen through the study that quercetin may act as a good inhibitor for treatment. With the help of an in silico study, it was easier to analyse the 3D structure of the protein, which may be scrutinized for the best-predicted model. Quercetin may work as a good inhibitor for treating Alzheimer's disease, according to in silico research using molecular docking and molecular dynamics simulations, and future in vitro and in vivo analysis may confirm its effectiveness.

Acute Flaccid Quadriparesis Because of a Rare Systemic Cause.

Sjogren's syndrome is a chronic slowly progressive autoimmune disease characterized by lymphocytic infiltration of exocrine glands resulting in xerostomia and dry eyes. The syndrome has wide clinical spectrum from organ specific exocrionopathy to systemic manifestation. The disease can present alone or with other autoimmune diseases like RA, SLE, Scleroderma, autoimmune thyroid disease etc. Prevalence of primary Sjogren's is 0.5-1% and of secondary Sjogren's is 5-20%. Renal involvement is rare and can either be tubulointerstial or glomerular. Based on biopsy reports in the available literature, tubulointerstitial nephritis (TIN) is the most common histological abnormality, followed by glomerulonephritis as a distant second.1 Distal Renal tubular Acidosis is the most common manifestation of TIN. We report a case of a 35 year female with acute onset motor weakness (quadriparesis) with hypokalemia with NAGMA with distal RTA. Patient was diagnosed with Secondary Sjogren's and managed accordingly.

A Multicentric, Randomized, Controlled Phase III Study of Centhaquine (Lyfaquin®) as a Resuscitative Agent in Hypovolemic Shock Patients.

INTRODUCTION: Centhaquine (Lyfaquin®) showed significant safety and efficacy in preclinical and clinical phase I and II studies. METHODS: A prospective, multicentric, randomized phase III study was conducted in patients with hypovolemic shock, systolic blood pressure (SBP) ≤ 90 mmHg, and blood lactate levels ≥ 2 mmol/L. Patients were randomized in a 2:1 ratio to the centhaquine group (n = 71) or the control (saline) group (n = 34). Every patient received standard of care (SOC) and was followed for 28 days. The study drug (normal saline or centhaquine 0.01 mg/kg) was administered in 100 mL of normal saline infusion over 1 h. The primary objectives were to determine changes (mean through 48 h) in SBP, diastolic blood pressure (DBP), blood lactate levels, and base deficit. The secondary objectives included the amount of fluids, blood products, and vasopressors administered in the first 48 h, duration of hospital stay, time in intensive care units, time on ventilator support, change in acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS), and the proportion of patients with 28-day all-cause mortality. RESULTS: The demographics of patients and baseline vitals in both groups were comparable. The cause of hypovolemic shock was trauma in 29.4 and 47.1% of control group and centhaquine group patients, respectively, and gastroenteritis in 44.1 and 29.4%, respectively. Shock index (SI) and quick sequential organ failure assessment at baseline were similar in the two groups. An equal amount of fluids and blood products were administered in both groups during the first 48 h of resuscitation. A lesser amount of vasopressors was needed in the first 48 h of resuscitation in the centhaquine group. An increase in SBP from baseline was consistently higher up to 48 h (12.9% increase in area under the curve from 0 to 48 h [AUC0-48]) in the centhaquine group than in the control group. A significant increase in pulse pressure (48.1% increase in AUC0-48) in the centhaquine group compared with the control group suggests improved stroke volume due to centhaquine. The SI was significantly lower in the centhaquine group from 1 h (p = 0.032) to 4 h (p = 0.049) of resuscitation. Resuscitation with centhaquine resulted in a significantly greater number of patients with improved blood lactate (control 46.9%; centhaquine 69.3%; p = 0.03) and the base deficit (control 43.7%; centhaquine 69.8%; p = 0.01) than in the control group. ARDS and MODS improved with centhaquine, and an 8.8% absolute reduction in 28-day all-cause mortality was observed in the centhaquine group. CONCLUSION: Centhaquine is an efficacious resuscitative agent for treating hypovolemic shock. The efficacy of centhaquine in distributive shock is being explored. TRIAL REGISTRATION: Clinical Trials Registry, India; ctri.icmr.org.in, CTRI/2019/01/017196; clinicaltrials.gov, NCT04045327.

Screening and identification of secondary metabolites in the bark of Bauhinia variegata to treat Alzheimer's disease by using molecular docking and molecular dynamics simulations.

Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) acts as a promising protein targets for which drug as an inhibitor can be designed to treat Alzheimer's Disease. Different flavonoids and alkaloids of Bauhinia variegata were used as an inhibitor to target the protein. The current in silico study was carried out to explore the binding patterns of flavanoids and alkaloids against Acetylcholinesterase (PDB ID: 4PQE) and Butyrylcholinesterase (PDB ID: 1P0I) using molecular docking and molecular dynamics simulations approach. Molecular docking result shows that Dihydroquercetin (CID:439533) binds with the active region of AChE and BChE. Using molsoft, molinspiration, and pkCSM all the properties of the candidate were analyzed. The best compound Dihydroquercetin was compared with Donepezil drug through molecular dynamic simulation studies. The analysis of Molecular Dynamics Simulations showed that AChE and AChE-Dihydroquercetin complex became stable at 3000 ps and there was little conformational change in BChE and BChE-Dihydroquercetin complex. The in silico study finally predicts that Dihydroquercetin may act as a good inhibitor for treating Alzheimer's disease and further in vitro and in vivo studies may prove its therapeutic potential.Communicated by Ramaswamy H. Sarma.

The Effect of Aerosolized Chlorpheniramine Maleate on Exercise Induced Bronchospasm and Gas Exchange in Asthmatics.

INTRODUCTION: Exercise induced asthma (EIB) is an acute, reversible, usually selflimiting airways obstruction which sets in after exercise in patients with asthma. One popular mechanism of EIA is the increase in histamine and its metabolites in circulation after exercise, which leads to bronchoconstriction via histamine receptors in bronchi. Chlorpheniramine Maleate is potent, less sedative antihistaminic drug, which acts by inhibiting histamine release from mast cells. It is also said to have anticholinergic properties. The aerosol route of administration of a drug has the advantages of a faster onset of action, fewer side effects, and greater protection against EIB with respect to small airways function. This study was conducted to evaluate the effect of Chlorpheniramine Maleate aerosol inhalation on flow volumes and gas exchange. MATERIALS AND METHODS: 25 established patients of stabilized bronchial asthma (18 to 44 years) with history of EIA attending Allergy OPD, Medical OPD or Chest clinic were included in the present study. Patients were studied for 3 days in a week at the same time of day. Baseline spirometry was done to know test parameters, i.e. FEV1, PEFR and FEF50%. Gas exchange study during rest including minute ventilation (VE), oxygen consumption (VO2), Carbon dioxide produced per minute (VCO2), Respiratory quotient (R) was carried out. Patient was asked to perform exercise on bicycle ergometer. During exercise VE, VO2, VCO2 and R were recorded every 30 seconds. FEV1, PEFR and FEF50% were recorded immediately after and 5 min after completion of exercise. On day 2, same procedure was repeated with saline nebulisation before the exercise. On day 3, aerosolized Chlorpheniramine Maleate was used instead of saline for nebulisation. Values obtained were tabulated and analysed. OBSERVATIONS AND RESULTS: After exercise FEV1, PEFR, FEF50% decreased on all three days, but the fall in these parameters was less on Day III (prior nebulisation with Chlorpheniramine maleate) compared to previous days. There was significant increase in FEV1, PEFR and FEF50% (P<0.01, 0.05 and 0.05 respectively) which was seen 30 mins after inhalation of Chlorpheniramine maleate aerosol compared to placebo. Resting and exercise values of Minute Ventilation (VE), oxygen uptake (VO2) carbon dioxide expired, on all the three days were comparable and statistically not significant by the end of exercise. On day 2 and 3, 'R' as compared to that of day1 was slightly significant during rest and initial minutes of exercise but became insignificant after that till the end of exercise. CONCLUSION: This study shows that Chlorpheniramine causes bronchodilation during resting period by acting on the circulating or tissue histamine in asthmatics which contributes to an increase in resting bronchomotor tone. As there is incomplete inhibition of EIA by Chlorpheniramine, there may be some other associated mediator release for pathogenesis of EIA.

Movement Disorder - A Rare Presentation of Diabetic Ketoacidosis.

ABSTRACT: Diabetic ketoacidosis is a common acute complication of Diabetes Mellitus. Diabetic ketoacidosis is known to cause impaired consciousness due to the osmolar and acid base imbalance which in turn cause central nervous system involvement. Here we report a rare presentation of Diabetic ketoacidosis with movement disorder in form of hemichorea and facial tics. The movement disorder improved with treatment of ketosis.

DRESS Syndrome.

Carbamazepine was and still used extensively in clinical practice in varied indications can cause adverse drug reaction shaving diverse clinical manifestations of variable severity. "Drug Reaction with Eosinophilia and Systemic Symptoms" (DRESS) syndrome is a severe, potentially life-threatening, acute adverse drug reactions, typically characterized by a long latency period from drug exposure. DRESS syndrome is characterized by the presence of fever, coetaneous eruptions, lymphadenopathy, internal organ involvement (such as hepatitis, carditis, interstitial nephritis, interstitial pneumonitis, etc.) and haematological abnormalities, mainly leucocytosis, eosinophilia and sometimes atypical lymphocytosis. We report a clinical case of DRESS syndrome with liver injury, evaluated with the RegiSCAR scoring system as a "definite case" possibly induced by carbamazepine in a patient.

Preparation of Sliver and Selenium Nanoparticles and Its Characterization by Dynamic Light Scattering and Scanning Electron Microscopy.

AIM: In our study, two different methods were used to determine the size and size distribution of the sliver and selenium nanoparticles via dynamic light scattering (DLS) and scanning electron microscopy (SEM). BACKGROUND: Nanotechnology dealing with metal and metalloid nanoparticles has been usually applied in nearly each field of science, engineering, and technology including biology and medicine etc due to presence of size and shape dependent unusual physical and chemical properties. In the most recent decade, numerous groups including appreciably developed metal and metalloid nanoparticles based theranostic approaches for the treatment of almost human diseases. Amongst many nanoparticles, recently silver and selenium nanoparticles have been broadly used in the antimicrobial coatings, textiles, paints, keyboards, engineering, food industry, electronics, cosmetics, bio-sensing, wound dressings, and even in biomedical devices. METHODS: In our study, silver nanoparticles were prepared by using the chemical reduction method. Selenium nanoparticles (SeNPs) were synthesized by the chemical reduction of sodium selenite by glutathione (reduced form) and stabilized by bovine serum albumin (BSA). Characterization of silver and selenium nanoparticles samples were analyzed by dynamic light scattering (DLS) and Scanning Electron Microscopy (SEM). CONCLUSIONS: Due to characterization by DLS technique, nanoparticles size was found the range of 79.22 nm and 178 nm for Sliver and Selenium Nanoparticles respectively. Sliver nanoparticles shown morphological average size and shape with SEM reveals spherical shape particles with the size of 80.32 nm whereas Selenium nanoparticles shown rod shape particles with the size of 74.29 nm.

Early Detection of Right Ventricular Dysfunction in Chronic Obstructive Pulmonary Disease by Echocardiography.

OBJECTIVE: This study is designed to investigate the effects of pulmonary arterial hypertension on RV systolic and diastolic functions in cases of COPD and to correlate RV systolic and diastolic functions with pulmonary arterial pressure. MATERIALS AND METHODS: 100 patients admitted in various medical wards of tertiary care Hospital and a primary care hospital with stable chronic obstructive pulmonary disease persons with age and sex-matched. 35 age and sex matched person without any associated and known disease were taken as control subjects. Selection of cases has been made on basis of detailed history, thorough clinical examination, electrocardiography, chest x-ray, pulmonary function tests. OBSERVATION: RV Systolic function (RVEF and RVWT) are significantly abnormal in patients of stable compensated COPD and they are significantly correlated with PAP(p< 0.002). RV diastolic function i.e., E/A ratio and PFR are altered in 60%(n-60) of patients of COPD studied against control subjects and significantly correlated with PAP(p< 0.002). CONCLUSION: Echocardiography is a non invasive method to detect changes of right ventricular dysfunctions in early stages with very good significant sensitivity and specificity.

Gas-containing Liver Abscess Mimicking Pneumoperitoneum.

Gas under the diaphragm or pneumoperitoneum, is often a sign of grave intra-abdominal pathology. It can be due to either of surgical or non-surgical etiology. Here we present a case of gas under right dome of diaphragm caused by a non-surgical cause i.e. secondary to aspiration of liver abscess.

Aetiopathogenesis of type-2 diabetes mellitus: could chronic stress play an important role?

OBJECTIVES: Pathogenesis of type-2 diabetes remains elusive. Various factors including diet, physical exercise, obesity, genetic factors and stress, have been discussed. Among these factors role of stress is still poorly understood in diabetes. Therefore the study was planned to assess effect of stress in diabetic and non-diabetic population in a comparative descriptive manner. METHODS: 1000 diabetic cases (group A) and equal number of healthy individuals were selected as a comparison group (group B). Both groups were examined at 0, 12, 24 months. To assess stress 17 points were examined (factors mainly related to emotions, hurriedness, relaxed status etc.), total 68 points for stress were given; > 30/68 was considered as severe stress. Mental health life style factors like duration of sleep and working mental hours were also examined. EEG and SSR were done at 24 months to assess stress and sympathetic response. RESULTS: There was presence of chronic stress, (> 90% had > 30/68 scoring) more mental work and less sleep duration in group A. EEG showed synchronised v/s desynchronised basal rhythm in group B v/s group A. SSR suggestive of increased sympathetic activity in group A. CONCLUSION: It is concluded that chronic stress leads to increased basal sympathetic activity, resulting from disturbed cortical hypothalamic axis, leading to central insulin resistance and diabetes.

Acute presentation of idiopathic thrombocytopenic purpura in postmenopausal woman.

A healthy 50 years old woman who had no past history of bruising or menometrorrhagia was admitted with complaints of cutaneous petechiae all over the body for 5 days and gum bleeding for 3 days. She presented with isolated thrombocytopenia, an otherwise unremarkable peripheral smear and physical examination showed evidence of bleeding consistent with low platelet count. After excluding other causes of thrombocytopenia, diagnosis of idiopathic thrombocytopenic purpura was made. She was given intravenous steroids and marked improvement in signs and symptoms was noted.

Auto-immune pancreatitis--an uncommon type of chronic pancreatitis.

Auto-immune pancreatitis is an increasingly recognised disorder of presumed auto-immune aetiology. It has to be differentiated from other forms of chronic pancreatitis and pancreatic cancer as it has dramatic response with steroid therapy. So, early and prompt diagnosis of this disorder in early stage of disease is essential. Here a case of auto-immune pancreatitis in a 16 years old young male is reported.

Mild cool air--a risk factor for asthma exacerbations: results of a retrospective study.

BACKGROUND AND OBJECTIVES: Worldwide incidence of bronchial asthma is on rise. Infections either viral or bacterial and various environmental factors are considered as major risk factors for exacerbations in various studies. Despite of awareness and preventive strategies to risk factors, exacerbations largely remain uncontrolled, therefore the study was planned to review the existing risk factors and to find out some other risk factor/factors which could help us in understanding the other causes of exacerbations. METHODS: The study was done in Ajmer, the central part of Rajasthan state, India, at Mittal Hospital & Research Centre and J. L. N. Medical college hospital by collecting data for the period of four years (January 2006 - December 2009). Monthly record of 300 regular cases of bronchial asthma was taken. This record included symptoms, history of exposure to various risk factors, and PEFR. Environmental data was also collected. On the basis of record monthly attack rate was calculated. RESULTS/OBSERVATIONS: Maximum attack rate (> 90%) was found in October, November (early winter) and February and March (spring) during all the four years studied except in October 2009. A common precipitant present during these months was mild cool air (environmental temperature of 23-27 degrees c). Attack rate was very less above and below of this temperature. No clear association was present with any other known precipitants. CONCLUSION: It is concluded that inhalation of mild coolair (23-27 degrees c) may be an important risk factor besides other risk factors for asthma exacerbation.