Synthesis, antimicrobial activity and absorption studies of some novel heterocyclic dyes based on 4-hexylbenzene-1,3-diol

Aniline derivatives were diazotized and coupled with 3-aminocrotononitrile to give the corresponding 2-arylhydrazono-3-ketiminobutyronitriles. Cyclization of these arylhydrazono derivatives with hydrazine monohydrate afforded 5-amino-4-arylazo-3-methyl-1H-pyrazoles which were subsequently diazotized and coupled with malononitrile to yield a series of pyrazolylhydrazonomalononitriles. These compounds were then reacted with hydrazine monohydrate to provide, heterocyclic dyes, which were further diazotized and coupled with 4-hexylbenzene-1,3-diol to produce novel heterocyclic tetraazo dyes which were characterized by elemental analysis and spectral methods. The antimicrobial activity and absorption characteristics of the dyes were also examined in detail

ROLE OF ORAL PANCREATIC ENZYME SUPPLEMENTATION IN PANCREATIC EXOCRINE DEFICIENCY

Objectives: The present study was carried out to study the role of oral pancreatic enzyme supplementation in pancreatic exocrine deficiency. Methods: This study included 50 consecutive cases of pancreatic exocrine deficiency. Diagnosis of pancreatic exocrine deficiency was made based on history, clinical examination, and contrast-enhanced computed tomography findings. Each patient was supplied with oral pancreatic enzyme supplements. Each patient was followed up for 1 year with three visits (3 months, 6 months, and 12 months) to assess changes in clinical features of pancreatic exocrine deficiency, change in nutritional status of the patient, and compliance with therapy. Results: At first follow-up visit (3 months), abdominal discomfort reduced in 17 previously symptomatic patients. Mean stool frequency reduced from 3.18 per day to 2.34 per day. Stool consistency improved with only 18 patients (36%) having liquid consistency stool in comparison to 76% at the time of initial presentation. Average body mass index (BMI) improved from baseline value of 20.648 kg/sqm to 20.674 kg/sqm. Average hemoglobin improved from 10.40 g/dL to 10.52 g/dL and average serum albumin remained static at 3.0 g/dL. At second follow-up visit (6 months), abdominal discomfort reduced in 20 previously symptomatic patients. Mean stool frequency reduced from 3.18 per day (primary survey) to 1.7 per day. Stool consistency improved with only 12 patients (24%) having liquid consistency stool in comparison to 76% at the time of initial presentation. Average BMI improved from baseline value of 20.648 kg/sqm to 21.062 kg/sqm. Average hemoglobin improved from 10.40 g/dL to 10.69 g/dL and average serum albumin improved from 3.0 g/dL at primary survey to 3.1 g/dL. At third follow-up visit (12 months), abdominal discomfort reduced in 30 previously symptomatic patients. Mean stool frequency reduced from 3.18 per day (primary survey) to 1.6 per day. Stool consistency improved with only 9 patients (18%) having liquid consistency stool in comparison to 76% at the time of initial presentation. Average BMI improved from baseline value of 20.648 kg/sqm to 21.402 kg/sqm. Average hemoglobin improved from 10.40 g/dL to 10.76 g/dL and average serum albumin improved from 3.0 g/dL at primary survey to 3.3 g/dL. Conclusion: In follow-up visits, there was an improvement in symptoms over 12 months. Abdominal discomfort and stool frequency reduced. Stool consistency improved. Nutritional parameters showed statistically significant improvement. Mean BMI of the study sample, mean hemoglobin, and serum albumin increased. The study provides rationale for using these clinical symptoms as surrogate markers for the efficacy of Pancreatic Enzyme Replacement Therapy in patients with pancreatic exocrine insufficiency

Can epigenetic and inflammatory biomarkers identify clinically aggressive prostate cancer?

Prostate cancer (PCa) is a highly prevalent malignancy and constitutes a major cause of cancer-related morbidity and mortality. It emerges through the acquisition of genetic and epigenetic alterations. Epigenetic modifications include DNA methylation, histone modifications and microRNA deregulation. These generate heritable transformations in the expression of genes but do not change the DNA sequence. Alterations in DNA methylation (hypo and hypermethylation) are the most characterized in PCa. They lead to genomic instability and inadequate gene expression. Major and minor-specific modifications in chromatin recasting are involved in PCa, with signs suggesting a dysfunction of enzymes modified by histones. MicroRNA deregulation also contributes to the initiation of PCa, including involvement in androgen receptor signalization and apoptosis. The influence of inflammation on prostate tumor carcinogenesis is currently much better known. Recent discoveries about microbial species resident in the urinary tract suggest that these are the initiators of chronic inflammation, promoting prostate inflammatory atrophy and eventually leading to PCa. Complete characterization of the relationship between the urinary microbiome and prostatic chronic inflammation will be crucial to develop plans for the prevention of PCa. The prevalent nature of epigenetic and inflammatory alterations may provide potential biomarkers for PCa diagnosis, treatment decisions, evaluation of prognosis and posttreatment surveillance.publishersversionpublishe

Estimation of the free-charge-carrier concentration in fast-ion conducting Na2S-B2S3 glasses from an analysis of the frequency-dependent

ac and dc conductivities of fast-ion conducting xNa2S+(1-x)B2S3 glasses in the composition range 0.001≤x≤0.1 were analyzed using the Almond-West formula σ(ν)=σdc[1+(ν/νH)α]. The hopping frequency for free charge carriers νH, the dc conductivity σdc, and their respective activation energies were determined. The concentration of free charge carriers evaluated from the conductivities and estimated mobilities is in good agreement with the overall content of sodium cations in the glasses and it is proposed that this supports the concept of a strong and not weak electrolyte model for these fast-ion conducting glasses

Synthesis of <i>N</i>-(4-chlorophenyl) substituted pyrano[2,3-c]pyrazoles enabling PKBβ/AKT2 inhibitory and <i>in vitro</i> anti-glioma activity

A series of N-(4-chlorophenyl) substituted pyrano[2,3-c]pyrazoles was synthesised and screened for their potential to inhibit kinases and exhibit anticancer activity against primary patient-derived glioblastoma 2D cells and 3D neurospheres. A collection of 10 compounds was evaluated against glioma cell lines, with compound 4j exhibiting promising glioma growth inhibitory properties. Compound 4j was screened against 139 purified kinases and exhibited low micromolar activity against kinase AKT2/PKBβ. AKT signalling is one of the main oncogenic pathways in glioma and is often targeted for novel therapeutics. Indeed, AKT2 levels correlated with glioma malignancy and poorer patient survival. Compound 4j inhibited the 3D neurosphere formation in primary patient-derived glioma stem cells and exhibited potent EC(50) against glioblastoma cell lines. Although exhibiting potency against glioma cells, 4j exhibited significantly less cytotoxicity against non-cancerous cells even at fourfold–fivefold the concentration. Herein we establish a novel biochemical kinase inhibitory function for N-(4-chlorophenyl) substituted pyrano[2,3-c]pyrazoles and further report their anti-glioma activity in vitro KEY MESSAGE: Anti-glioma pyrano[2,3-c]pyrazole 4j inhibited the 3D neurosphere formation in primary patient-derived glioma stem cells. 4j also displayed PKBβ/AKT2 inhibitory activity. 4j is nontoxic towards non-cancerous cells

Draft genome sequence of Pseudomonas fuscovaginae, a broad-host-range pathogen of plants.

addresses: International Centre for Genetic Engineering & Biotechnology, Trieste, Italy.notes: PMCID: PMC3347198types: Journal Article; Research Support, Non-U.S. Gov'tFreely available on Open AccessPseudomonas fuscovaginae was first reported as a pathogen of rice causing sheath rot in plants grown at high altitudes. P. fuscovaginae is now considered a broad-host-range plant pathogen causing disease in several economically important plants. We report what is, to our knowledge, the first draft genome sequence of a P. fuscovaginae strain