PMP22 Gene–Associated Neuropathies: Phenotypic Spectrum in a Cohort from India

Journal of Molecular Neuroscience - Reports of spectrum of clinical manifestations in PMP22 gene–associated neuropathies (duplication/mutations) are scarce. To identify the frequency of PMP22...     

Ligand-dependent activation of ER{beta} lowers blood pressure and attenuates cardiac hypertrophy in ovariectomized spontaneously hypertensive rats

AIMS: The biological effects of oestrogens are mediated by two different oestrogen receptor (ER) subtypes, ERalpha and ERbeta, which might play different, redundant, or opposing roles in cardiovascular disease. Previously, we have shown that the selective ERalpha agonist 16alpha-LE2 improves vascular relaxation, attenuates cardiac hypertrophy, and increases cardiac output without lowering elevated blood pressure in spontaneously hypertensive rats (SHR). Because ERbeta-deficient mice exhibit elevated blood pressure and since the ERbeta agonist 8beta-VE2 attenuated hypertension in aldosterone-salt-treated rats, we have now tested the hypothesis that the isotype-selective ERbeta agonist 8beta-VE2 might be capable of lowering elevated blood pressure in ovariectomized SHR. METHODS AND RESULTS: Treatment of ovariectomized SHR with 8beta-VE2 for 12 weeks conferred no uterotrophic effects but lowered elevated systolic blood pressure (-38 +/- 5 mmHg, n = 31, P < 0.001 vs. placebo) as well as peripheral vascular resistance (-31.3 +/- 4.6%, P < 0.001 vs. placebo). 8beta-VE2 enhanced aortic ERbeta expression (+75.7 +/- 7.1%, P < 0.01 vs. placebo), improved NO-dependent vasorelaxation, augmented phosphorylation of the vasodilator-stimulated phosphoprotein in isolated aortic rings (P < 0.05 vs. placebo), increased cardiac output (+20.4 +/- 2.5%, P < 0.01 vs. placebo), and attenuated cardiac hypertrophy (-22.2 +/- 3.2%, p < 0.01 vs. placebo). 8beta-VE2, in contrast to oestradiol, did not enhance cardiac alpha-myosin heavy chain expression. CONCLUSION: Ligand-dependent activation of ERbeta confers blood pressure lowering effects in SHR that are superior to those of 17beta-estradiol or the ERalpha agonist 16alpha-LE2 and attenuates cardiac hypertrophy primarily by a reduction of cardiac afterload without promoting uterine growth.     

Rosmarinic acid attenuates hepatic steatosis by modulating ER stress and autophagy in oleic acid-induced HepG2 cells

Non-alcoholic fatty acid disease (NAFLD) has become an emerging entity of liver disorders worldwide. Oxidative stress and deranged autophagy-induced endoplasmic reticulum (ER) stress has recently been recognized as one of the prime factors involved in the pathological mechanism underlying NAFLD and progressive non-alcoholic steato-hepatitis (NASH). Epidemiological and experimental data reveal the potency of dietary polyphenols in averting NAFLD. In this line, to analyse and address the underlying pathogenic mechanisms, in the present study, oleic acid-induced HepG2 cells were treated with rosmarinic acid (RA), a dietary polyphenol with well-established cytoprotective properties. Treatment with rosmarinic acid (20 μg) was found to potently counter the elevated levels of total cholesterol (TC) and triglycerides (TG). Additionally, exposure of oleic acid-induced HepG2 cells to rosmarinic acid showed reduced levels of ROS and increased activity of enzymic and non-enzymic antioxidants. The steatotic HepG2 cells presented a pronounced increase in the expression of key ER stress markers such as p-PERK, p-IRE-1, ATF-6, p-eIF-α and CHOP, which was considerably reduced upon treatment with rosmarinic acid. Moreover, exposure to rosmarinic acid altered the deranged autophagic mechanism in oleic acid-induced HepG2 cells, which was observed via the protein expression of Beclin 1, LC31, ATG5 and ATG7. This study demonstrates that rosmarinic acid abrogates NAFLD via diminishing ER stress by nullifying oxidative stress and restoring deranged autophagy and can be used as a potent adjunct in the treatment of NAFLD, thus illustrating the valuable application of polyphenols in combating NAFLD.

Non-alcoholic fatty acid disease (NAFLD) has become an emerging entity of liver disorders worldwide.     

Reepithelialization of orthotopic tracheal allografts prevents rejection after withdrawal of immunosuppression

Prior work has demonstrated that immunosuppressed orthotopic tracheal allografts undergo progressive reepithelialization over a 48-day period with recipient-derived tracheal epithelium. We hypothesized that reepithelialization of tracheal allografts would prevent rejection after withdrawal of immunosuppression. BALB/c murine tracheal grafts were transplanted orthotopically into either syngeneic or allogeneic C57/BL6 recipients. The recipients were either not immunosuppressed, immunosuppressed with cyclosporine A (10 mg/kg per day) continuously, or immunosuppressed for 48 days and then withdrawn from immunosuppression. The grafts were assessed for acute and chronic rejection 10 days and 50 days after immunosuppression withdrawal. The immunosuppressed allograft recipients maintained a ciliated epithelium acutely and chronically after immunosuppression withdrawal. Ten days after immunosuppression withdrawal, there was a mild cellular infiltrate, which resolved 50 days after withdrawal. Electron microscopy, lymphocyte subpopulation assays, and lamina propria analysis demonstrated that immunosuppression withdrawal did not result in tracheal allograft rejection. In vitro and in vivo assessments did not demonstrate evidence of systemic or local immune tolerance. We conclude that reepithelialization of orthotopic tracheal allografts with recipient-derived mucosa prevents rejection of allograft segments. Tracheal transplantation may require only transient immunosuppression, which can be withdrawn after tracheal reepithelialization.     

Primary sphenoid sinus esthesioneuroblastoma

Esthesioneuroblastoma is a rare malignant tumor of undifferentiated neuroectodermal origin. Because these tumors are derived from olfactory epithelium, most cases arise in the superior nasal cavity at the level of the cribriform niche. The development of an esthesioneuroblastoma outside of the region in which olfactory epithelium exists is exceedingly rare. We report a rare case of a primary sphenoid sinus esthesioneuroblastoma and discuss the pathogenesis, clinical presentation, and treatment of this rare entity.     

Microscopic Agglutination Test Analysis Identifies Prevalence of Intermediate Species Serovars in Ruminants in Endemic States of India

Serological survey was carried out in order to investigate the seroprevalence of leptospirosis in ruminants in coastal regions (flood prone areas) of endemic states (Andhra Pradesh, Gujarat, Kerala, Maharashtra and Tamil Nadu) of India using non-purposive samples collected during the year 2011 and 2012. A total of 553 serum samples (Cattle-332; Buffaloes-85; Goats-107 and Sheep-29) collected randomly from twenty one coastal districts of five states were tested at 1:100 dilution in microscopic agglutination test using 14 reference leptospira serovars. The overall seroprevalence of 24.96 % (138/553) with 20.48 % in cattle, 20 % in buffaloes, 58.62 % in sheep and 38.3 % in goats was observed. The results of χ² tests revealed that the seroprevalance in cattle across different districts (regions) in each of the surveyed states are not associated except in Kerala (χ² = 33.98, p < 0.05). In other species (buffalo, sheep and goat) also there is no association of seroprevalance across different districts in each of the states. Among the targeted endemic states, high prevalence was observed in Maharashtra (19/53 = 35.85 %) followed by Kerala (52/165 = 31.51 %), Andhra Pradesh (16/50 = 32 %), Gujarat (48/212 = 22.64 %) and Tamil Nadu (3/72 = 4.17 %). Out of 138 reacted sera, 37 samples showed multiple reactivities with 26.81 % prevalence. The predominant leptospiral antibodies were determined against frequency of distribution of the serovars Hardjo (28.99 %) followed by Kaup (18.12 %), Pomona (15.94 %), Bankinang (14.49 %). This study supports that ruminants may have a role in maintaining intermediate species serovar Kaup apart from being a well-known reservoir for Hardjo serovar in endemic states of India.