Expert Opinion on Novel Fixed Drug Combination of Metformin Sustained Release and Vildagliptin Immediate Release for Type 2 Diabetes Mellitus Management in India

Type 2 Diabetes Mellitus (T2DM) is a highly prevalent cardiometabolic disorder in India and is further projected to rise (10.4% by 2030). In newly diagnosed patients, maintaining HbA1c 6.5-7.0% and minimizing glycaemic exposure, particularly during the first year following diagnosis, may be crucial for preventing complications. Early treatment initiation with a synergistic combination of vildagliptin and metformin is one of the many possible combinations to manage type 2 diabetes mellitus. In view of emerging clinical evidence on early initiation of combination therapy than monotherapy with metformin, there is a need for expert consensus on the use of the current approved Fixed Dose Combination (FDC) of Metformin SR + Vildagliptin IR in newly diagnosed diabetic patients. Experts framed final consensus statements based on available scientiûc evidence, experience and collective clinical judgment from practical experience this FDC.

Positioning of the fixed dose combination of Rosuvastatin + Clopidogrel + Aspirin in the Treatment of Cardiovascular Diseases

Dual anti-platelet therapy (DAPT) and statins are recommended by guidelines for the management of cardiovascular diseases (CVDs), even though the duration of treatment is guided by ischemic and bleeding risk. Clopidogrel and aspirin are the most commonly used DAPT in CVDs. Adding a statin to DAPT is helpful in reducing the thrombosis risk. Fixed-dose combination (FDC) therapy in CVD can help to address the factors of convenience, compliance, control, cost, and complication better than free drug combinations. Therefore, the FDC of rosuvastatin (10 mg or 20 mg) + clopidogrel (75 mg) + aspirin (75 mg) is likely to improve compliance in CVD patients, thereby reducing adverse cardiovascular outcomes and cost of treatment. There is lack of awareness on long term benefits of this FDC in Indian patients.

Placement of Oral Formulations of Brivaracetam in Various Patient Profiles: An Indian Perspective

Brivaracetam (BRV), an analog of levetiracetam (LEV), lowers seizure frequency through a unique mechanism. Although BRV is approved for focal epilepsy in patients aged >1 month (by the US Food and Drug Administration) or >16 years (in India), clinical studies have suggested its potential role in other indications such as generalized seizures, secondarily generalized tonic-clonic seizures, and drug-resistant focal epilepsy, and in certain special populations. Here, we discuss the potential role of BRV in different patient populations and present expert opinions for positioning the pre-existing and newly available oral formulations of BRV to aid both clinicians and diverse patient groupswith a simple and easy dosing and titration-based treatment, including safe and effective switching from LEV to BRV.

Brivaracetam Intravenous Formulation in Epilepsy Management in India : A Position Statement

Brivaracetam (BRV), a propyl analog of levetiracetam, has been shown to be safe and effective in Indian patients with uncontrolled focal epilepsy. A series of advisory board meetings involving pediatricians, neurologists, and physicians were held across India to evaluate the role of IV BRV in India and formulate a position statement. The panelists opined that the potential role of BRV in the acute management of increased seizure activity, especially status epilepticus, should be explored in the Indian context. Further, there is a dearth of Indian studies on the use of BRV in epilepsy patients aged below 16 years. IV BRV holds great potential to be the therapy of choice in epilepsy management owing to the fast mode of action and lesser risk of adverse effects.

Pattern of Alcohol Consumption in Patients of Alcoholic Liver Disease in India

Background: Alcohol-related chronic liver disease (ALD) and its complications are major causes of morbidity and mortality. Predisposing factors for ALD include the amount, type, duration of alcohol consumption, patient’s genetic predisposition, race, sex, and other comorbid conditions. Aims: To study the dose, duration, and type of alcohol consumption in ALD and the effect of these parameters on severity and outcome Methods: This was a prospective study conducted at the Department of Gastroenterology, SMS hospital, Jaipur, between December 2017 to December 2018. All patients with alcoholic liver disease admitted in the department were consecutively enrolled. Data relating to dose, duration, type, alcohol intake pattern, biochemical, ultrasonographic, and clinical parameters were analysed. Results: One hundred ten patients (age 43.5±9.9, all-male) were studied. Mean alcohol consumption was 130.47±35.37gm/day. Sixty-three (57.3%) patients consumed <120gm, 25(22.7%) between 120-239gm, while 22(20%) patients consumed =240gm of alcohol per day. The mean duration of alcohol consumption was 15.89±6.57 years. Fifty-nine (53.63%) patients consumed country-made spirit, 25 (22.72%) branded spirit, 23 (20.91%) mixed or variable type, while three (2.73%) patients consumed only wine. The occurrence of hepatic encephalopathy (HE) was significantly associated with dose (p <0.001) and type (p <0.001) of alcohol consumption. MELD Na score significantly correlated (r=0.48, p <0.001) with dose of alcohol. Conclusion: Our study found a dose-dependent relationship of alcohol intake with hepatic encephalopathy and MELD-Na score. The incidence of ALD did not change with the type of alcohol consumed. Low lymphocyte counts were significantly associated with dose and duration of alcohol intake.

Effect of premedication on postoperative pain after root canal therapy in patients with irreversible pulpitis:a systematic review and meta-analysis

This systematic review aimed to assess the effect of premedication on postoperative pain after root canal treatment in vital teeth. Five electronic databases were searched for randomized clinical trials, and two independent reviewers selected eligible studies, extracted data, and assessed the quality of studies using the Cochrane Risk of Bias tool. Meta-analysis was conducted using the random-effects model, and the pooled effect estimate of the standardized mean difference (SMD) between premedication and placebo was calculated. Subgroup analysis was conducted based on the class and route of the drug. Studies with a high risk of bias were excluded from the sensitivity analysis. Ten trials satisfied the inclusion criteria, of which eight were included in the meta-analysis. Premedication was more effective in reducing postoperative pain than placebo at 6 hours (SMD = -1.00; 95% confidence interval [CI] = -1.33 to -0.66), 12 hours (SMD = -0.80; 95% CI = -1.05 to -0.56), and 24 hours (SMD = -0.72; 95% CI = -1.02 to -0.43). The results of the sensitivity analysis confirmed the findings of the primary analysis. Based on these results, it can be concluded that premedication is effective in reducing postoperative pain in teeth with irreversible pulpitis. However, additional quality studies are required for further validation.

Effect of premedication on postoperative pain after root canal therapy in patients with irreversible pulpitis:a systematic review and meta-analysis

This systematic review aimed to assess the effect of premedication on postoperative pain after root canal treatment in vital teeth. Five electronic databases were searched for randomized clinical trials, and two independent reviewers selected eligible studies, extracted data, and assessed the quality of studies using the Cochrane Risk of Bias tool. Meta-analysis was conducted using the random-effects model, and the pooled effect estimate of the standardized mean difference (SMD) between premedication and placebo was calculated. Subgroup analysis was conducted based on the class and route of the drug. Studies with a high risk of bias were excluded from the sensitivity analysis. Ten trials satisfied the inclusion criteria, of which eight were included in the meta-analysis. Premedication was more effective in reducing postoperative pain than placebo at 6 hours (SMD = -1.00; 95% confidence interval [CI] = -1.33 to -0.66), 12 hours (SMD = -0.80; 95% CI = -1.05 to -0.56), and 24 hours (SMD = -0.72; 95% CI = -1.02 to -0.43). The results of the sensitivity analysis confirmed the findings of the primary analysis. Based on these results, it can be concluded that premedication is effective in reducing postoperative pain in teeth with irreversible pulpitis. However, additional quality studies are required for further validation.

Development and validation of stability indicating liquid chromatographic (RP-HPLC) method for estimation of ubidecarenone in bulk drug and formulations using quality by design (QBD) approach

ABSTRACT A novel, accurate, precise and economical stability indicating Reverse Phase-High Performance Liquid Chromatography (RP-HPLC) method, was developed and validated for the quantitative determination of ubidecarenone (UDC) in bulk drug, UDC marketed formulation and UDC loaded cubosomes (CBMs) nanocarriers through Response surface methodology (RSM) design with three factors and three levels was performed to optimize the chromatographic variables followed by forced degradation studies of UDC were performed to detect degradation peak. RP-HPLC separation was achieved using mobile phase consisting of Acetonitrile:Tetrahydrofuran:Deionised water in the ratio 55:42:3 and a flow rate of 1.0 mL/min was optimized with a standard retention time (Rt) of 2.15 min, through experiment. The method was found linear in the concentration range of 5-100 µg/mL with a regression coefficient of 0.999. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 3.04 µg/mL and 9.11 µg/mL, respectively.

Endodontic management of a maxillary first molar with seven root canals using spiral computed tomography

The main objective of this case report is to present a rare root canal configuration of maxillary molar with seven root canals; three mesiobuccal, two palatal and two dis-tobuccal canals diagnosed during treatment procedure confirmed by spiral computed tomography. A thorough knowledge of root canal morphology, proper clinical and radiographic examination, and use of dental operating microscopes are necessary for successful clinical outcomes. This article highlights the variations in the morphology of maxillary first molar and use of the latest techniques in successful diagnosis and negotiation of the additional canals

Phytochemical composition and in vitro antioxidant activity of aqueous extract of Aerva lanata (L.) Juss. ex Schult. Stem (Amaranthaceae)

OBJECTIVE@#To analyze the phytochemical composition and in vitro antioxidant properties of aqueous extract of Aerva lanata (A. lanata) stem.@*METHODS@#During the preliminary phytochemical analysis, the aqueous extract of A. lanata was screened for the presence of carbohydrates, proteins, phenolic compounds, oil and fats, saponins, flavonoids, alkaloids, tannins and phytosterols. Antioxidant activity of the extract was determined by 2, 2-diphenyl-1-picrylhydrazyl radical scavenging activity, metal chelating activity, reducing power activity and DNA damage inhibition activity. Analysis of phenolic compounds was performed by Folin-Ciocalteau reagent method and gradient high performance liquid chromatography technique.@*RESULTS@#Preliminary phytochemical analysis exhibited the presence of phenolic compounds, saponins, flavonoids, tannins and phytosterols as major phytochemical groups. The extract exhibited high 2, 2-diphenyl-1-picrylhydrazyl radical scavenging activity (IC(50)= 110.74 μg/mL), metal chelating activity (IC(50)= 758.17 μg/mL), reducing power activity and DNA damage inhibition efficiency. The extract was reported to possess a high amount of total phenolic content and some of them were identified as gallic acid (3,4,5-OH), apigenin-7-O-glucoside (apigetrin), quercetin-3-O-rutinoside (rutin) and myricetin (3,5,7,3,4,5-OH) by high performance liquid chromatography analysis. The extract was found non toxic towards human erythrocytes in the hemolytic assay (IC(50) = 24.89 mg/mL).@*CONCLUSIONS@#These results conclud that A. lanata stem possesses high antioxidant activity and can be used for the development of natural and safe antioxidant compounds.

Antioxidant activity of newly discovered lineage of marine actinobacteria

OBJECTIVE@#To investigate the antioxidant activity of marine actinobacteria.@*METHODS@#The content of total phenolics, the level of antioxidant potential by DPPH radical scavenging activity, metal chelating activity, FRAP method, β carotene assay and NO scavenging activity in extract were determined.@*RESULTS@#In all the methods the extract exhibited good scavenging activity except NO scavenging activity. The IC(50) values of marine actinobacteria extract on DPPH radical were found to be 41.09 μg/mL. The zone of color retention was 12 mm in β-carotene bleaching assay. DNA protective efficiency of the extracts was also studied using UV-photolysed H(2)O(2)-driven oxidative damage to pBR322. HPLC analysis identified some of the major phenolic compounds in extracts, which might be responsible for the antioxidant potential and cyto-protection. It showed a 100% cytotoxic effect in brine shrimp lethality assay within 10 mins. The novel actinobacteria was identified as Streptomyces LK-3 (JF710608) through 16S rDNA Sequencing.@*CONCLUSIONS@#The results obtained suggest that the extracts bear anti-cancer metabolites and could be considered as a potential source for anti-cancer drug development.

Studies on antioxidative enzymes induced by cadmium in pea plants (Pisum sativum).

Pea plants (Pisum sativum cv. Swati) exposed to different concentration of cadmium (50, 100, 200 9M Cd) under controlled glass house conditions were quantified for different physiological parameters and antioxidative enzymes. In pea plants, Cd produced a significant inhibition of growth and induced chlorosis, marginal yellowing and necrosis in young leaves, the effect being most pronounced at 200 9M Cd supply. An alteration in the activated oxygen metabolism of pea plants were also detected as evidenced by an increase in concentration of H2O2 and TBARS along with decrease in the chlorophyll and carotenoid concentration in leaves. Cadmium toxicity induced an increase in non- protein thiol, ascorbate, proline and cysteine concentration. A significant increment in the activity of SOD, APX and GR, and a decrease in CAT was observed as a result of Cd treatment. The enhanced activity of SOD and inhibition of CAT and POD produces a high build up of H2O2 which appears to be the main cause of oxidative stress due to Cd toxicity in pea plants.

Psychotropic Drug Induced Metabolic Disorders.

According to a report from the Centers for Disease Control and Prevention released in April, the leading cause of death contibuting to that shortened lifespan is not the patients’ mental illness, but rather something largely preventable cardiovascular disease. Metabolic disorders are known complications of newer antipsychotics. The term Metabolic Syndrome refers to a syndrome consisting of central obesity as indicated by excessive visceral fat, plasma lipid abnormalities, glucose dysregulation, and high blood pressure. The metabolic syndrome develops gradually, different drugs have differential propensity to cause it. This is a dreadful condition as it induces medical morbidities, which may be life threatening in patients. The criteria for diagnosing the metabolic syndrome propsed by the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) are the most current and widely used but are not universally accepted. Common manifestations are dyslipidemia, hypertension, weight gain, increase in blood glucose etc. This review covers the latest available information on the drug — induced metabolic syndrome. Risk factors and mechanisms are discussed.