OPTIMIZATION OF EXTRACTION PARAMETERS FOR TOTAL FLAVONOIDS FROM GARDENIA GUMMIFERA GUM RESIN BY RESPONSE SURFACE METHODOLOGY

Objective: To optimize the extraction parameters for determining the highest yield of Total Flavonoids from Gardenia gummifera gum resin.Methods: In the present study, response surface methodology (RSM) with three level Box Behenken design (BBD) was performed to optimize extraction parameters for total flavonoids. Solvent concentration(A), extraction time (B) and extraction temperature(C) were considered for single factor experiment.Results: The highest flavonoid concentration was obtained with acetone 45.00% v/v, time 101.46 min, temperature 41.57 °C. The average experimental TFC under optimal conditions was 161.14 mg/g which was in close agreement with the predicted value of 163.42 mg/g.Conclusion: RSM-BBD is successfully applied in optimizing extraction conditions for extraction of total flavonoids from G. gummifera gum resin

Pattern of drug utilization in pediatric out patient department of a tertiary care teaching hospital

Background: Drug utilization studies have special significance among paediatric age groups as infant and children represent about 42% of the population in developing countries. This is the vital period of rapid growth and development. Therefore, drugs should be used very cautiously and rationally among these sub groups. The present study is conducted to analyse the prescribing pattern of drugs in paediatric age group for various illnesses. Methods: It was a prospective observational study, conducted in paediatric outpatient department of Raja Rajeswari medical college and research hospital for a period of 6 months after obtaining approval from institutional ethical committee. Descriptive statistical was used to determine the frequency, percentages, mean and standard deviation.Results: In the present study, fever (30.8%) followed by respiratory diseases were most common diseases seen. The commonly used drugs include antipyretics (66%), antimicrobials (53.6%), cough syrups (34.4%), antihistaminic (31.2%) and nasal decongestants (23.2%). Prescribing indicator shows existence of polypharmacy. Prescribing drugs by generic name was seen only in 8.1% and 47.82% of the drugs were prescribed from EDL. The frequency of use of injectables in our study was 5.8%. Conclusions: Irrational use of antibiotics and polypharmacy needs to be curbed. Prescribing drugs in their generic name and prescribing drugs from EDL need to be promoted. The present prescribing pattern can be improved by advocating rational drug prescribing, patient education and improving hospitals

Study on assessment of awareness about concepts in undergraduate pharmacology curriculum among clinicians in a tertiary care teaching hospital

Background: Rational prescribing forms the corner stone of successful implementation of rational drug use. To boost the cause of rational use of Medicine, the P-drug concept was given in late nineties. The idea was to make Physicians familiar with few personal drugs chosen from National Essential drug list based on efficacy, safety, suitability and cost. The present study was conducted to assess the awareness of clinicians about basic pharmacological concepts.Methods: It is a cross sectional study with a study population of 100, conducted in RRMCH for a period of one month. It is a questionnaire based study involving clinicians and post graduates working in this hospital. Descriptive statistical analysis has been carried out in the present study.Results: In our study, 38% of physicians were aware of the term Essential drugs and 26% of doctors prescribed drugs from National Essential drug list. 56% of respondents were aware of term rational drug use but only 1/3 of them were aware of adverse effects, drug interactions of the drugs they prescribed. Majority of physicians (85%) used standard text book as the source of drug information.Conclusions: Lack of knowledge among physicians about new concepts like p-drug, rational drug use and essential drugs points towards need for having more CMEs on basic pharmacological concepts

Study on antihyperglycemic effect of bromocriptine in dexamethasone induced hyperglycemic wistar rats

Background: Diabetes mellitus is a chronic metabolic disorder that develops due to insulin deficiency or insulin resistance. Recent animal and human studies have reported bromocriptine to be effective in the management of type 2 diabetes mellitus. The present study was done to evaluate the antihyperglycemic effect of bromocriptine in dexamethasone induced hyperglycemic rats.Methods: Male wistar rats were used and divided into 5 groups. Dexamethosone was used to induce hyperglycemia in group B-E. Group A was the untreated control group, group B was the standard control group, group C was the oral 10 mg/kg of bromocriptine dissolved in 0.9% normal saline, group D was the oral 20 mg/kg metformin dissolved in 0.9% normal saline, group E was the oral 10 mg/kg bromocriptine+20 mg/kg metformin dissolved in 0.9% normal saline. Fasting blood glucose, post prandial blood glucose and body weight was estimated on day 1, 15, 30.Results: It was seen that dexamethasone induced hyperglycemia and increase in body weight in male wistar rats, which were significantly controlled by oral bromocriptine and bromocriptine with metformin combination.Conclusions: Results obtained from this study showed that bromocriptine can be a promising drug with novel mechanism to treat type 2 diabetes mellitus

Synthesis, and biological screening of chloropyrazine conjugated benzothiazepine derivatives as potential antimicrobial, antitubercular and cytotoxic agents

A series of twenty new chloropyrazine conjugated benzothiazepines (22-41) have been synthesized with 58%–95% yields. The compounds were characterized by using different spectroscopic techniques including FT-IR, ¹H NMR, ¹³C NMR spectroscopy and mass spectrometry. The synthesized compounds (22-41) and their precursor chalcones (2-21) were evaluated for antitubercular and cytotoxic activities. Additionally, compounds 22-41 were also tested for antimicrobial activity. Among the chalcone series (2-21), compounds 7 and 14 showed significant antitubercular activities (MICs 25.51 and 23.89 µM, respectively), whereas among benzothiazepines (22-41), compounds 27 and 34 displayed significant antimicrobial (MICs 38.02 µM, 19.01 µM) and antitubercular (MIC 18.10 µM) activities. Compounds 7 and 41 displayed cytotoxic activities with IC₅₀ of 46.03 ± 1 and 35.10 ± 2 µM respectively. All the compounds were evaluated for cytotoxic activity on normal human liver cell lines (L02) and found to be relatively less selective towards this cell line. The most active compounds identified through this study could be considered as potential leads for the development of drugs with possible antimicrobial, antitubercular, and cytotoxic activities

Therapeutic Strategies and Biomarkers to Modulate PARP Activity for Targeted Cancer Therapy

Poly-(ADP-ribose) polymerase 1 (PARP1) is commonly known for its vital role in DNA damage response and repair. However, its enzymatic activity has been linked to a plethora of physiological and pathophysiological transactions ranging from cellular proliferation, survival and death. For instance, malignancies with BRCA1/2 mutations heavily rely on PARP activity for survival. Thus, the use of PARP inhibitors is a well-established intervention in these types of tumors. However, recent studies indicate that the therapeutic potential of attenuating PARP1 activity in recalcitrant tumors, especially where PARP1 is aberrantly overexpressed and hyperactivated, may extend its therapeutic utility in wider cancer types beyond BRCA-deficiency. Here, we discuss treatment strategies to expand the tumor-selective therapeutic application of PARP inhibitors and novel approaches with predictive biomarkers to perturb NAD+ levels and hyperPARylation that inactivate PARP in recalcitrant tumors. We also provide an overview of genetic alterations that transform non-BRCA mutant cancers to a state of “BRCAness” as potential biomarkers for synthetic lethality with PARP inhibitors. Finally, we discuss a paradigm shift for the use of novel PARP inhibitors outside of cancer treatment, where it has the potential to rescue normal cells from severe oxidative damage during ischemia-reperfusion injury induced by surgery and radiotherapy

Antitubercular activity assessment of fluorinated chalcones, 2-aminopyridine-3-carbonitrile and 2-amino-4H-pyran-3-carbonitrile derivatives: In vitro, molecular docking and in-silico drug likeliness studies

A series of newer previously synthesized fluorinated chalcones and their 2-amino-pyridine-3-carbonitrile and 2-amino-4H-pyran-3-carbonitrile derivatives were screened for their in vitro antitubercular activity and in silico methods. Compound 40 (MIC~ 8 μM) was the most potent among all 60 compounds, whose potency is comparable with broad spectrum antibiotics like ciprofloxacin and streptomycin and three times more potent than pyrazinamide. Additionally, compound 40 was also less selective and hence non-toxic towards the human live cell lines-LO2 in its MTT assay. Compounds 30, 27, 50, 41, 51, and 60 have exhibited streptomycin like activity (MIC~16–18 μM). Fluorinated chalcones, pyridine and pyran derivatives were found to occupy prime position in thymidylate kinase enzymatic pockets in molecular docking studies. The molecule 40 being most potent had shown a binding energy of -9.67 Kcal/mol, while docking against thymidylate kinase, which was compared with its in vitro MIC value (~8 μM). These findings suggest that 2-aminopyridine-3-carbonitrile and 2-amino-4H-pyran-3-carbonitrile derivatives are prospective lead molecules for the development of novel antitubercular drugs

Design, Facile Synthesis and Characterization of Dichloro Substituted Chalcones and Dihydropyrazole Derivatives for Their Antifungal, Antitubercular and Antiproliferative Activities

Infectious diseases caused by fungi and mycobacteria pose an important problem for humankind. Similarly, cancer is one of the leading causes of death globally. Therefore, there is an urgent need for the development of novel agents to combat the deadly problems of cancer, tuberculosis, and also fungal infections. Hence, in the present study, we designed, synthesized, and characterized 30 compounds including 15 chalcones (2–16) and 15 dihydropyrazoles (17–31) containing dichlorophenyl moiety and also screened these compounds for their antifungal, antitubercular, and antiproliferative activities. Among these compounds, the dihydropyrazoles showed excellent antifungal and antitubercular activities whereas the chalcones exhibited promising antiproliferative activity. Among the dihydropyrazoles, compound 31 containing 2-thienyl moiety showed promising antifungal activity (MIC 5.35 µM), whereas compounds 22 and 24 containing 2,4-difluorophenyl and 4-trifluoromethyl scaffolds revealed significant antitubercular activity with the MICs of 3.96 and 3.67 µM, respectively. Compound 16 containing 2-thienyl moiety in the chalcone series showed the highest anti-proliferative activity with an IC₅₀ value of 17 ± 1 µM. The most active compounds identified through this study could be considered as starting points in the development of drugs with potential antifungal, antitubercular, and antiproliferative activities

Effect of physiotherapy on single breath count and breath holding time in COVID-19 patients

Background: The novel Coronavirus is known to primarily affect the respiratory system and physiotherapy treatment is integral to combat this infection. However, the assessment of pulmonary function poses a difficult challenge considering the risk of spread of infection and sanitisation of the devices used. Single breath count (SBC) and breath holding time (BHT) can be thus adopted as bedside assessment tests for pulmonary function following physiotherapy treatment.Method: In this a retrospective observational study of 51 COVID-19 patients, mean age 51.7±14.56 years, on room air, admitted in the step-down units of a tertiary care hospital. Patients received standard physiotherapy treatment, within safe hemodynamic limits. Pre and post treatment session SBC was recorded in 32 patients and BHT in 19 patients. Three reading were noted and the best of three readings were used for analysis.Results: The paired t test was used to analyse SBC and BHT. Mean pre and post SBC was 18.25±8.96 and 23.31±9.96 respectively with a mean difference of 5.06 and p<0.0001. Mean pre and post BHT were 19.37 and 23.05 seconds respectively with a mean difference of 3.68 and p<0.0001.  Statistically significant difference in the pre and post treatment session SBC and BHT was observed, indicating a positive effect of physiotherapy treatment on pulmonary function.Conclusion: Physiotherapy treatment shows significant improvement in the pulmonary function in COVID-19 patients. SBC and BHT tests can be used as assessment and prognostic tools for pulmonary function in COVID-19 patients

All-sky search for short gravitational-wave bursts in the second Advanced LIGO and Advanced Virgo run

We present the results of a search for short-duration gravitational-wave transients in the data from the second observing run of Advanced LIGO and Advanced Virgo. We search for gravitational-wave transients with a duration of milliseconds to approximately one second in the 32-4096 Hz frequency band with minimal assumptions about the signal properties, thus targeting a wide variety of sources. We also perform a matched-filter search for gravitational-wave transients from cosmic string cusps for which the waveform is well modeled. The unmodeled search detected gravitational waves from several binary black hole mergers which have been identified by previous analyses. No other significant events have been found by either the unmodeled search or the cosmic string search. We thus present the search sensitivities for a variety of signal waveforms and report upper limits on the source rate density as a function of the characteristic frequency of the signal. These upper limits are a factor of 3 lower than the first observing run, with a 50% detection probability for gravitational-wave emissions with energies of ∼10-9 Mc2 at 153 Hz. For the search dedicated to cosmic string cusps we consider several loop distribution models, and present updated constraints from the same search done in the first observing run