RP-HPLC METHOD DEVELOPMENT AND VALIDATION FOR THE COMBINATION OF IMIQUIMOD AND SALICYLIC ACID

Objective: The present study was undertaken to develop and validate an RP-HPLC method for the combination of imiquimod and salicylic acid Methods: The method was carried out on Nucleodur C18 (250 mm × 4.6 mm I.D., 5 ????m) using low-pressure gradient elution mode. The mobile phase was used as 30M potassium dihydrogen phosphate and acetonitrile (45:55) pH 6.5 adjusted using ortho-phosphoric acid. The concentration of solvents was 1-20 µg/ml and the volume of injection was 20 mcl with the flow rate of 1.0 ml/min. The absorption maxima of salicylic acid and imiquimod were found 234 nm and 226 nm, respectively. Results: The method was validated and showed the linearity greater than 0.99% and with precision (RSD%<1). The limit of detection (LOD) and limit of quantification (LOQ) of salicylic acid was found to be 0.09756 µg/ml and 0.2956 µg/ml, respectively, and imiquimod was found to be 0.044031 µg/ml and 0.13334 µg/ml, respectively. Conclusion: The method developed in the present study was found to be sensitive, specific, and can be applied for the simultaneous estimation of imiquimod and salicylic acid

Clinical Utility of Vitamin D3 As Potent Biomarker in Cardiovascular and Liver Disorders

Vitamin D is lipophilic substance needed for calcium and phosphate balance and the regulation of the osteo-metabolic system.The purpose of the study was to look at the possible significance of Vitamin D3 as a biomarker for liver enzymes and cholesterol. 249 cases were analysed, with different combinations of liver enzymes, vitamin D3, and cholesterol.75 clinical samples were processed over the course of the 3year study.46(61.3%) were females and 29 (38.6%) were males.Males were more affected than females.In respect to Vitamin D3, the age group of 41-60 years had a large range of cholesterol levels and liver enzyme values. 11% of cases had high SGOT levels, while 13% had aberrant cholesterol values.Above the age of 60, there was a linear connection between cholesterol and liver enzymes.There was seasonal variations in serum 25-OHD levels.Winter (November-March) indicated a Vitamin D3 deficiency in the blood serum, accounting for 74 cases(66%).Autumn and summer had the best range, with only 0 and 16 cases (14.2%), respectively.Despite wide variability in serum vitamin D levels, the differences were not statistically significant.Vitamin D3 can be an important biomarker in clinical practice since it can aid in the early detection of potential hazards linked with cardiovascular disease and liver dysfunction

IMPORTANCE OF NANOCARRIERS AND PROBIOTICS IN THE TREATMENT OF ULCERATIVE COLITIS

Ulcerative colitis (UC) is an inflammatory chronic disease primarily affecting the colonic mucosa; the extent and severity of colon involvement are variable. Ulcerative colitis is identified by mucus diarrhea, tenesmus, bowel distension, and anemia. 5-aminosalicylic acid drugs, steroids, and immune suppressants are used for the therapy of ulcerative colitis. The mainchallenges in the management of thediseaseare drug-related side-effects and local targeting. To overcome these challengesprobiotics and micro and Nanoparticulate systemauspiciousapproaches to overcome drug-related adverse side effects and local targeting.Upon ingestion, the probiotics can result in beneficial health effects. Probiotics and micro and nanoparticulate approaches for suitable targeting and overcome the drug-associated side effect. Probiotics are mainly used as gut modulators but are also nowadays explored for their use in ulcerative colitis.The current therapeutic goals are to achieve clinical remission along with mucosal healing, avoidance of complications such as side effects of the drug and to improve the quality of life. The use of probiotics to increase the health of the intestine and used to block or manage intestinal disorders. They may prevent the induction of inflammatory reactions. Probiotics must be inspected for efficacy in the prevention and management of a wide spectrum of gastrointestinal diseases, like antibiotic-associated diarrhea.Micro and Nanoparticulate drug delivery system has been achieving huge importance for targeting of the drug to colon locally at a controlled and sustained rate

Evaluation of Plant Growth-Promoting and Salinity Ameliorating Potential of Halophilic Bacteria Isolated From Saline Soil

Among the biotic and abiotic stress affecting the physical, chemical, and biological properties of soil, salinity is a major threat that leads to the desertification of cultivable land throughout the world. The existence of diverse and versatile microbial populations inhabiting the nutrient-rich soil and varied soil conditions affects the soil dynamism. A normal soil constitutes 600 million bacteria belonging to about 20,000 species, which is reduced to 1 million with 5,000-8,000 species in stress conditions. Plant growth-promoting rhizobacteria (PGPR) are in symbiotic association with the plant system, which helps in combating the abiotic stress and increases the overall productivity and yield. These microorganisms are actively associated with varied cellular communication processes through quorum sensing and secondary metabolites such as the production of Indole-3-acetic acid (IAA), exopolysaccharide (EPS) siderophore, ammonia, ACC deaminase, and solubilization of phosphate. The present study focused on the isolation, identification, and characterization of the microorganisms isolated from the seacoast of Dandi, Navsari. Twelve isolates exhibited PGP traits at a high salt concentration of 15-20%. AD9 isolate identified as Bacillus halotolerans showed a higher ammonia production (88 +/- 1.73 mu g/mL) and phosphate solubilization (86 +/- 3.06 mu g/mL) at 15% salt concentration, while AD32* (Bacillus sp. clone ADCNO) gave 42.67 +/- 1.20 mu g/mL IAA production at 20% salt concentration. AD2 (Streptomyces sp. clone ADCNB) and AD26 (Achromobacter sp. clone ADCNI) showed ACC deaminase activity of 0.61 +/- 0.12 and 0.60 +/- 0.04 nM alpha-ketobutyrate/mg protein/h, respectively. AD32 (Bacillus sp. clone ADCNL) gave a high siderophore activity of 65.40 +/- 1.65%. These isolates produced salinity ameliorating traits, total antioxidant activities, and antioxidant enzymes viz. superoxide dismutase (SOD), Glutathione oxidase (GSH), and catalase (CAT). Inoculation of the multipotent isolate that produced PGP traits and salinity ameliorating metabolites promoted the plant growth and development in rice under salinity stress conditions. These results in 50% more root length, 25.00% more plant dry weight, and 41% more tillers compared to its control.Peer reviewe

Breast cancer hypofractionated radiotherapy in 2-weeks with 2D technique: 5-year clinical outcomes of a phase 2 trial

BACKGROUND: To report clinical outcomes and late toxicities of a 2-week hypofractionated post-operative loco-regional radiotherapy in patients with breast cancer. MATERIALS AND METHODS: This trial was approved by the Institutional Ethics Committee and registered with gov, no. NCT02460744. Between June 2013 and October 2014, 50 patients with breast cancer, post mastectomy or breast conserving surgery (BCS) were included in this study, of whom 10 had BCS. Patients were planned on a 2-dimentional (2D) simulator with 2 tangential fields and an incident supraclavicular field. Radiotherapy dose was 34 Gy/10#/2 weeks and a sequential boost of 10 Gy/5#/1 wk in BCS patients. The primary endpoint was the rate of acute skin toxicities previously reported. Here, we report the secondary end points of late toxicities, cosmesis, local recurrence, disease-free survival (DFS) and overall survival (OS). Late skin toxicities were recorded according to the Radiotherapy and Oncology Group (RTOG) scoring criteria. Cosmetic outcomes were assessed using the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/RTOG breast cosmesis and the Late Effects Normal Tissue/Subjective Objective Management Analytic (LENT/SOMA) scales for the breast and chest wall, respectively. Kaplan-Meier estimates of DFS and OS were calculated, and 5-year DFS and OS rates (with approximate 95% CIs) were estimated. RESULTS: Late grade ≥ 2 chest wall induration, hypopigmentation and subcutaneous fibrosis were seen in 3 (6%), 3 (6%) and 1 (2%) patients, respectively. Chest wall cosmesis was excellent/good in 34 (72%) and fair/bad in 13 (28%) patients. In BCS patients, grade 2 skin induration, subcutaneous fibrosis and edema was observed in 1 patient (11%) each. Cosmesis was excellent/good in 7 (78%) and fair/bad in 2 (22%) patients. Late grade ≥ 2 arm edema, pain and shoulder stiffness were reported by 1 (2%), 2 (4%) and 2 (4%) patients, respectively. No local recurrences were observed. Five patients developed distant metastases (10%). Seven patients died (14%). The 5-year DFS and OS rate was 90% (95% CI: 77–96%) and 88% (95% CI: 75–94%), respectively. CONCLUSION: Hypofractionated radiotherapy in 2 weeks in patients with breast cancer was associated with minimal late toxicity, good cosmetic outcome and excellent local control. This trial may be of relevance for developing countries where resources are limited.

Common variants in CLDN2 and MORC4 genes confer disease susceptibility in patients with chronic pancreatitis

A recent Genome-wide Association Study (GWAS) identified association with variants in X-linked CLDN2 and MORC4 and PRSS1-PRSS2 loci with Chronic Pancreatitis (CP) in North American patients of European ancestry. We selected 9 variants from the reported GWAS and replicated the association with CP in Indian patients by genotyping 1807 unrelated Indians of Indo-European ethnicity, including 519 patients with CP and 1288 controls. The etiology of CP was idiopathic in 83.62% and alcoholic in 16.38% of 519 patients. Our study confirmed a significant association of 2 variants in CLDN2 gene (rs4409525—OR 1.71, P = 1.38 x 10-09; rs12008279—OR 1.56, P = 1.53 x 10-04) and 2 variants in MORC4 gene (rs12688220—OR 1.72, P = 9.20 x 10-09; rs6622126—OR 1.75, P = 4.04x10-05) in Indian patients with CP. We also found significant association at PRSS1-PRSS2 locus (OR 0.60; P = 9.92 x 10-06) and SAMD12-TNFRSF11B (OR 0.49, 95% CI [0.31–0.78], P = 0.0027). A variant in the gene MORC4 (rs12688220) showed significant interaction with alcohol (OR for homozygous and heterozygous risk allele -14.62 and 1.51 respectively, P = 0.0068) suggesting gene-environment interaction. A combined analysis of the genes CLDN2 and MORC4 based on an effective risk allele score revealed a higher percentage of individuals homozygous for the risk allele in CP cases with 5.09 fold enhanced risk in individuals with 7 or more effective risk alleles compared with individuals with 3 or less risk alleles (P = 1.88 x 10-14). Genetic variants in CLDN2 and MORC4 genes were associated with CP in Indian patients

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe

Molecular and cellular pathophysiology of circulating cardiomyocyte-specific cell free DNA (cfDNA): Biomarkers of heart failure and potential therapeutic targets

Pathological cardiac damage during heart failure is associated with cell death and damage associated molecular patterns (DAMPs) release which triggers a viscous cycle of sterile inflammation to mediate maladaptive cardiac tissue remodelling during the progression to heart failure. DAMPs like cytokines, chemokines, and nuclear or mitochondrial genomic fragments are released in the pathological myocardium. Interestingly, circulating or cytosolic DNA fragments can play a role in the disease by interaction with nucleic acid sensors expressed in cardiomyocyte and non-myocyte neighbouring cells. The circulating cell free DNA (cfDNA) fragments have been clinically reported as markers for various diseases including cardiovascular pathophysiology. Such cfDNA within the DAMP pool can mediate intra- and inter-cellular signalling cascade to upregulate transcriptional expression of inflammatory mediators and trigger oxidative stress within cells. The cellular role of such genomic equivalents varying with chronic or acute stress might be correlated with the cell death forms encountered in myocardium during disease progression. Thus, cfDNA can be phenotypically correlated as a critical player towards upregulation of pathological processes like interstitial fibrosis, cardiomyocyte contractile dysfunction and cell death. Herein, we review the association of cfDNA with heart failure and analyse their potential usage as novel and effective therapeutic targets towards augmentation of cardiac function