Recent advances in toxicological research of di-(2-ethylhexyl)-phthalate: Focus on endoplasmic reticulum stress pathway.

The plasticizer di-(2-ethylhexyl)-phthalate (DEHP) is the most significant phthalate in production, usage, and environmental occurrence. DEHP is found in products such as personal care products, furniture materials, cosmetics, and medical devices. DEHP is noncovalently bind with plastic therefore, repeated uses lead to leaching out of it. Exposure to DEHP plasticizers leads to toxicity in essential organs of the body through various mechanisms. The main objective of this review article is to focus on the DEHP-induced endoplasmic reticulum (ER) stress pathway implicated in the testis, brain, lungs, kidney, heart, liver, and other organs. Not only ER stress, PPAR-related pathways, oxidative stress and inflammation, Ca2+ homeostasis disturbances in mitochondria are also identified as the relative mechanisms. ER is involved in various critical functions of the cell such as Protein synthesis, protein folding, calcium homeostasis, and lipid peroxidation but, DEHP exposure leads to augmentation of misfolded/unfolded protein. This review complies with various recently reported DEHP-induced toxicity studies and some pharmacological interventions that have been shown to be effective through ER stress pathway. DEHP exposure does assess health risks and vulnerability to populations across the globe. This study offers possible targets and approaches for addressing various DEHP-induced toxicity.

Environmental toxicants and nephrotoxicity: Implications on mechanisms and therapeutic strategies.

Kidneys are one of the most important organs in the human body. In addition to filtering 200 liters of fluid every 24 hours, the kidney also regulates acid-base balance, maintains electrolyte balance, and removes waste and toxicants from the body. Nephrotoxicity is the term used to describe the deterioration of kidney function caused by the harmful effects of medications and various types of environmental toxicants. Exposure to environmental toxicants is an inevitable side effect in the world's increasing industrialization and even more prevalent in underdeveloped nations. Growing data over the past few years has illuminated the probable connection between environmental toxicants and nephrotoxicity. Phthalates, microplastics, acrylamide and bisphenol A are environmental toxicants of particular concern, which are known to have nephrotoxic effects. Such toxicants may accumulate in the kidneys of humans after being consumed, inhaled, or come into contact with the skin. They can enter cells through endocytosis and accumulate in the cytoplasm. Small-sized nephrotoxicants can cause a variety of ailments including inflammation with increased production of pro-inflammatory cytokines, oxidative stress, mitochondrial dysfunction, autophagy, and apoptosis. This study uncovers the potential for new insights concerning the relationship between various environmental toxicants and kidney health. The objectives of this review is to establish information gaps, assess and identify the toxicity mechanisms of different nephrotoxicants, identify innovative pharmacological therapies that demonstrate promising therapeutic benefits/ relevance, and discuss the predictions for the future based on the analysis of the literature.

Azilsartan Ameliorates Skeletal Muscle Wasting in High Fat Diet (HFD)-induced Sarcopenic Obesity in Rats via Activating Akt Signalling Pathway.

An association between the loss of skeletal muscle mass and obesity in the geriatric population has been identified as a disease known as sarcopenic obesity. Therefore, therapeutic/preventive interventions are needed to ameliorate sarcopenia. The present study investigates the effect of azilsartan (AZL) on skeletal muscle loss in High-Fat Diet (HFD)-induced sarcopenic obese (SO) rats. Four- and fourteen-months male Sprague Dawley rats were used and randomized in control and azilsartan treatment. 14 months animals were fed with HFD for four months and labeled as HFD-fed SO rats. Young & old rats received 0.5% carboxymethyl cellulose as a vehicle/AZL (8 mg/kg, per oral) treatment for six weeks. Grip strength and body composition analysis were performed after the last dose of AZL. Serum and gastrocnemius (GN)muscles were collected after animal sacrifice. AZL treatment significantly increased lean muscle mass, grip strength, myofibrillar protein, and antioxidant (superoxide dismutase & nitric oxide) levels in SO rats. AZL also restored the muscle biomarkers (creatine kinase, myostatin & testosterone), and insulin levels. AZL improves cellular, and ultracellular muscle structure and prevents type I to type II myofiber transitions in SO rats. Further, immunohistochemistry results showed increased expressions of pAkt and reduced expression of MuRF-1 and TNF-α exhibiting that AZL intervention could decrease protein degradation in SO rats. In conclusion, present results showed that AZL significantly increased lean mass, and restored muscle biomarkers, and muscle architecture. Taken together, the aforementioned findings suggest that azilsartan could be a possible therapeutic approach to reduce muscle wasting in sarcopenic obesity.

Health data from diaries used in low-income communities, north India.

OBJECTIVE: To determine the acceptability of keeping a self-written health diary among members of low-income communities, with the aim of generating needed health data. METHODS: We identified three different types of impoverished communities (tribal, inner-city slum and rural) in north India, and conducted a baseline survey to establish the sociodemographic properties of the members of 595 (tribal), 446 (slum) and 51 (rural) households. We designed health diaries with a single page to fill in per month, each with a carbon duplicate, and distributed diaries to willing participants. Health volunteers visited households each month to assist with diary completion and to collect duplicate pages for a period of one year. We compared the frequency of illnesses reported in health diaries with baseline survey data. FINDINGS: A total of 4881 diary users (tribal: 2205; slum: 2185; rural: 491) participated in our project. In terms of acceptability, 49.6% (1093/2205), 64.7% (1413/2185) and 79.0% (388/491) at the tribal, slum and rural sites, respectively, expressed satisfaction with the scheme and a willingness to continue. In the tribal and slum areas, we observed increased reporting of illnesses from health diaries when compared with baseline data. We observed that influenza-like illnesses were reported with the highest frequency of 58.9% (2972/5044) at the tribal site. CONCLUSION: We observed high levels of acceptability and participation among the communities. From our initial field studies, we have observed the benefits to both our study participants (timely preventive education and referrals) and to service providers (obtaining health data to allow improved planning).

Epithelioid hemangioendothelioma of hypopharynx: A rare presentation.

Epithelioid hemangioendothelioma is a rare vascular neoplasm of borderline or low-grade malignant potential uncommonly seen in head and neck region and has not been reported in the hypopharynx. We present here a case of epithelioid hemangioendothelioma arising from the hypopharynx in a young female patient who presented with progressive dysphagia for 1-year and difficulty in breathing for 1-month. This is first reported case in published English literature to the best of our knowledge. Recognition of this borderline entity is necessary because of its potential for malignant transformation and recurrence. A wide excision and regular clinical follow-up would be an appropriate treatment protocol. The role of other therapeutic modalities such as chemotherapy and/or radiotherapy is not yet well established.

Aortopulmonary Window With Anomalous Coronary Arteries.

Aortopulmonary window associated with anomalous origin of the right coronary artery from the main pulmonary artery is rare. We report a four-month-old male presenting with anomalous origin of both right and left coronary arteries from a single ostium from the anterior sinus of the pulmonary artery along with aortopulmonary window (APW). The patient was managed successfully with a pericardial baffle shunting the coronary ostium to the aorta through the APW.

Early and six-month assessment of bi-ventricular functions following surgical closure of atrial septal defect.

BACKGROUND: The effect of surgical closure of atrial septal defect (ASD) on biventricular functions is not well studied. We studied effect of surgical closure of ASD on bi-ventricular functions. METHODS: Patients undergoing surgical closure of ASD from December 2007 to June 2009 had 3 sequential echocardiograms examination: pre-procedure, post surgery at 1-month and at 6-month of follow up. Pulse Doppler velocities across mitral and tricuspid valves were measured as peak early diastolic (E wave) and peak late diastolic (A wave). Tissue Doppler velocities across lateral wall of both right ventricle (RV) and left ventricle (LV) were measured as peak early diastolic (E'), peak late diastolic (A'), and peak systolic (S') wave. Radionuclide angiography was performed to assess RV and LV ejection fraction at baseline and at 1-month follow up. RESULTS: The mean age of 20 enrolled patients was 21.85 ± 10.9 years; 8 females & 12 males. Trans-tricuspid flow velocities significantly decreased following surgery at one and 6-month (p < 0.005). There was no significant change in trans-mitral flow velocities at one and 6-months. Tricuspid and mitral E/A ratio and E/E' ratio also had an insignificant change following surgery. There was no significant change in LV ejection fraction as assessed by echocardiography (p = 0.132) and radionuclide scan (p = 0.143). Right ventricular ejection fraction had a significant improvement at 1-month of follow up (p = 0.005). CONCLUSIONS: There was a significant improvement in RV systolic function and an insignificant change in RV and LV diastolic functions following surgical closure of ASD.

Giant left ventricular pseudoaneurysm presenting with hemoptysis.

Left ventricular (LV) pseudoaneurysm is a late mechanical complication of myocardial infarction (MI). A giant LV pseudoaneurysm is a rare presentation. We report a case of a giant LV pseudoaneurysm in a post MI patient, who presented with hemoptysis. Hemoptysis is a rare clinical presentation of LV pseudoaneurysm. The patient had successful surgical repair of the aneurysm and had a favorable outcome in 9 mo' follow-up. The imaging modalities and surgical treatment of a pseudoaneurysm is discussed.

Structures, energetics, vibrational spectra of NH4+ (H2O)(n=4,6) clusters: Ab initio calculations and first principles molecular dynamics simulations.

Important structural isomers of NH(4) (+)(H(2)O)(n=4,6) have been studied by using density functional theory, Moller-Plesset second order perturbation theory, and coupled-cluster theory with single, double, and perturbative triple excitations [CCSD(T)]. The zero-point energy (ZPE) correction to the complete basis set limit of the CCSD(T) binding energies and free energies is necessary to identify the low energy structures for NH(4) (+)(H(2)O)(n=4,6) because otherwise wrong structures could be assigned for the most probable structures. For NH(4) (+)(H(2)O)(6), the cage-type structure, which is more stable than the previously reported open structure before the ZPE correction, turns out to be less stable after the ZPE correction. In first principles Car-Parrinello molecular dynamics simulations around 100 K, the combined power spectrum of three lowest energy isomers of NH(4) (+)(H(2)O)(4) and two lowest energy isomers of NH(4) (+)(H(2)O)(6) explains each experimental IR spectrum.