Synthesis and colon-specific drug delivery of a poly(acrylic acid-co-acrylamide)/MBA nanosized hydrogel

Intravenous administration of 5-fluorouracil (5-FU) for colon cancer therapy produces severe systemic side-effects due to its cytotoxic effect on normal cells. The main objective of the present study was to develop novel oral site-specific delivery of 5-FU to the colon with less drug being released in the stomach or small intestine using biodegradable hydrogel, hydrogel nanoparticles and comparing the targeting efficiency of 5-FU to colon from both. Poly(acrylic acid-co-acrylamide) (P(AA-co-Am)) normal hydrogel and hydrogel nanoparticles (HN) were synthesized by free radical polymerization using N,N-methylene-bis-acrylamide (MBA) as cross-linker, potassium persulfate as reaction initiator and 5-FU was loaded. HN were found to be degradable in physiological medium and showed comparatively higher swelling in rat caecal medium (RCM). 5-FU entrapment was increased by increasing Am (wt%) monomer feed. In vitro release of 5-FU from normal hydrogel and HN in pH progressive medium, it was found that a AA/Am ratio of 25:75 showed higher release in RCM. The Higuchi model yielded good adjustment of in vitro release kinetics. A higher amount of 5-FU reached the colon in HN (61 +/- 2.1%) than normal hydrogel (40 +/- 3.6%) by organ biodistribution studies in albino rats.     

Anthropometric indicators of obesity for identifying cardiometabolic risk factors in a rural Bangladeshi population

Aims/Introduction

The aim of the present study was to evaluate the predictive ability of body mass index (BMI), waist circumference (WC), waist‐to‐hip ratio (WHR), waist‐to‐height ratio (WHtR) and body fat percentages (BF%) for the presence of cardiometabolic risk factors, namely type 2 diabetes (DM), hypertension (HTN), dyslipidemia and metabolic syndrome (MS).

Materials and Methods

A total of 2293 subjects aged ≥20 years from rural Bangladesh were randomly selected in a population‐based, cross‐sectional survey. The association of anthropometric indicators with cardiometabolic risk conditions was assessed by using receiver operating characteristic curve analysis and adjusted odds ratios (ORs) for DM, HTN, dyslipidemia and MS.

Results

Area under the curve cut‐off values showed that the association of WHR, BF% and WC was higher than that for other indices for DM, HTN and MS, respectively, for both sexes, and WHtR for men and WHR for women for dyslipidemia. The ORs were highest for WHR for DM and WC for MS for both sexes, and WHtR for men and WC for women for HTN and dyslipidemia, respectively. The optimal cut‐off values for obesity for the present study in men and women showed BMIs of 22 and 22.8 kg/m², WHRs of 0.93 and 0.87, WHtRs of 0.52 and 0.54, BF% of 21.4 and 32.4%, and WCs of 82 and 81 cm, except for MS, which were 90 for men and 80 for women.

Conclusions

Compared with BMI, measures of central obesity, particularly WHR, WC, WHtR and BF%, showed a better association with obesity‐related cardiometabolic risk factors for both sexes.     

Consequences of bile salt biotransformations by intestinal bacteria

Emerging evidence strongly suggest that the human “microbiome” plays an important role in both health and disease. Bile acids function both as detergents molecules promoting nutrient absorption in the intestines and as hormones regulating nutrient metabolism. Bile acids regulate metabolism via activation of specific nuclear receptors (NR) and G-protein coupled receptors (GPCRs). The circulating bile acid pool composition consists of primary bile acids produced from cholesterol in the liver, and secondary bile acids formed by specific gut bacteria. The various biotransformation of bile acids carried out by gut bacteria appear to regulate the structure of the gut microbiome and host physiology. Increased levels of secondary bile acids are associated with specific diseases of the GI system. Elucidating methods to control the gut microbiome and bile acid pool composition in humans may lead to a reduction in some of the major diseases of the liver, gall bladder and colon.     

Termites as Structural Pest: Status in Indian Scenario

In this status paper, impact of termites as serious structural insect-pests is highlighted with relevant information in Indian context. Worldwide, more than $40 billion was estimated towards the termite damage. Study revealed at least thirteen species of termites belonging to three families are closely associated with structural damage in India. Heterotermes indicola (Rhinotermitidae: Isoptera) was discussed as the key termite species causing structural damage with substantial impact (even with astounding cases of abandoning houses by victimized villagers). Swarming, the most important sign of termite infestation in and around buildings/structures is discussed. A nation-wide scenario of termite damage in various buildings, public places, dams and dykes, agri-horticultural constructions and timber-in-service are presented. Sustainable termite control in the light of present and upcoming eco-technologies is identified as the major focal point. Use of termiticides as recognized and recommended by Indian Standards, Insecticide Act (1968) and United Nation Environment Program for management of termites in pre- and post-construction stages of various buildings and other structures are recorded with relevance of application and dose. Termite management technologies like use of borate, bait and barrier (3B) are briefed; with pest-control industry-invented devices such as termatrac are brought into focus along with indigenous traditional knowledge of termite control. Status of termite R&D in India is discussed in various institutional and web-based levels along with recognizing research gaps. The present study is a pioneer approach in its kind which can be a platform to formulate compact eco-friendly, environmentally sustainable and economic module of termite control interventions indoor.     

Identification of Microcystis aeruginosa Peptides Responsible for Allergic Sensitization and Characterization of Functional Interactions between Cyanobacterial Toxins and Immunogenic Peptides

Background

The cyanobacterium species Microcystis aeruginosa produces microcystin and an array of diverse metabolites believed responsible for their toxicity and/or immunogenicity. Previously, chronic rhinitis patients were demonstrated to elicit a specific IgE response to nontoxic strains of M. aeruginosa by skin-prick testing, indicating that cyanobacteria allergenicity resides in a non-toxin–producing component of the organism.

Objectives

We sought to identify and characterize M. aeruginosa peptide(s) responsible for allergic sensitization in susceptible individuals, and we investigated the functional interactions between cyanobacterial toxins and their coexpressed immunogenic peptides.

Methods

Sera from patients and extracts from M. aeruginosa toxic [MC(+)] and nontoxic [MC(–)] strains were used to test IgE-specific reactivity by direct and indirect ELISAs; 2D gel electrophoresis, followed by immunoblots and mass spectrometry (MS), was performed to identify the relevant sensitizing peptides. Cytotoxicity and mediator release assays were performed using the MC(+) and MC(–) lysates.

Results

We found specific IgE to be increased more in response to the MC(–) strain than the MC(+) strain. This response was inhibited by preincubation of MC(–) lysate with increasing concentrations of microcystin. MS revealed that phycocyanin and the core-membrane linker peptide are the responsible allergens, and MC(–) extracts containing these proteins induced β-hexosaminidase release in rat basophil leukemia cells.

Conclusions

Phycobiliprotein complexes in M. aeruginosa have been identified as the relevant sensitizing proteins. Our finding that allergenicity is inhibited in a dose-dependent manner by microcystin toxin suggests that further investigation is warranted to understand the interplay between immunogenicity and toxicity of cyanobacteria under diverse environmental conditions.

Citation

Geh EN, Ghosh D, McKell M, de la Cruz AA, Stelma G, Bernstein JA. 2015. Identification of Microcystis aeruginosa peptides responsible for allergic sensitization and characterization of functional interactions between cyanobacterial toxins and immunogenic peptides. Environ Health Perspect 123:1159–1166; http://dx.doi.org/10.1289/ehp.1409065