Emblica Officinalis: A Novel Therapy for Acute Pancreatitis — An Experimental Study

Acute necrotising pancreatitis is associated with an unacceptably high mortality for which no satisfactory remedy exists. Emblica officinalis (E.o.) is a plant prescribed in Ayurveda, the Indian traditional system of medicine, for pancreas-related disorders. This study was carried out to evaluate the protective effect of E.o. against acute necrotising pancreatitis in dogs. Pancreatitis was induced by injecting a mixture of trypsin, bile and blood into the duodenal opening of the pancreatic duct. Twenty eight dogs were divided into 4 groups (n = 6-8 each): GpI–control, GpII–acute pancreatitis, GpIII–sham-operated, GpIV–pretreatment with 28 mg E.o./kg/day for 15 days before inducing pancreatitis. Serum amylase increased from 541.99 ± 129.13 IU/ml to 1592.63 ± 327.83 IU (p<0.02) 2 hrs after the induction of pancreatitis in GpII. The rise in serum amylase in both GpIII and GpIV was not significant. On light microscopic examination, acinar cell damage was less and the total inflammatory score was significantly lower in the E.o. treated group as compared to GpII. Electron microscopy confirmed this and showed an increased amount of smooth, endoplasmic reticulum and small, condensed granules embedded in a vacuole. More studies are needed to explore the clinical potential of E.o. and its mechanism of action

A Hydrophobic Gate in an Ion Channel: The Closed State of the Nicotinic Acetylcholine Receptor

The nicotinic acetylcholine receptor (nAChR) is the prototypic member of the `Cys-loop' superfamily of ligand-gated ion channels which mediate synaptic neurotransmission, and whose other members include receptors for glycine, gamma-aminobutyric acid, and serotonin. Cryo-electron microscopy has yielded a three dimensional structure of the nAChR in its closed state. However, the exact nature and location of the channel gate remains uncertain. Although the transmembrane pore is constricted close to its center, it is not completely occluded. Rather, the pore has a central hydrophobic zone of radius about 3 A. Model calculations suggest that such a constriction may form a hydrophobic gate, preventing movement of ions through a channel. We present a detailed and quantitative simulation study of the hydrophobic gating model of the nicotinic receptor, in order to fully evaluate this hypothesis. We demonstrate that the hydrophobic constriction of the nAChR pore indeed forms a closed gate. Potential of mean force (PMF) calculations reveal that the constriction presents a barrier of height ca. 10 kT to the permeation of sodium ions, placing an upper bound on the closed channel conductance of 0.3 pS. Thus, a 3 A radius hydrophobic pore can form a functional barrier to the permeation of a 1 A radius Na+ ion. Using a united atom force field for the protein instead of an all atom one retains the qualitative features but results in differing conductances, showing that the PMF is sensitive to the detailed molecular interactions.Comment: Accepted by Physical Biology; includes a supplement and a supplementary mpeg movie can be found at http://sbcb.bioch.ox.ac.uk/oliver/download/Movies/watergate.mp

Novel associations for hypothyroidism include known autoimmune risk loci

Hypothyroidism is the most common thyroid disorder, affecting about 5% of the general population. Here we present the first large genome-wide association study of hypothyroidism, in 2,564 cases and 24,448 controls from the customer base of 23andMe, Inc., a personal genetics company. We identify four genome-wide significant associations, two of which are well known to be involved with a large spectrum of autoimmune diseases: rs6679677 near _PTPN22_ and rs3184504 in _SH2B3_ (p-values 3.5e-13 and 3.0e-11, respectively). We also report associations with rs4915077 near _VAV3_ (p-value 8.3e-11), another gene involved in immune function, and rs965513 near _FOXE1_ (p-value 3.1e-14). Of these, the association with _PTPN22_ confirms a recent small candidate gene study, and _FOXE1_ was previously known to be associated with thyroid-stimulating hormone (TSH) levels. Although _SH2B3_ has been previously linked with a number of autoimmune diseases, this is the first report of its association with thyroid disease. The _VAV3_ association is novel. These results suggest heterogeneity in the genetic etiology of hypothyroidism, implicating genes involved in both autoimmune disorders and thyroid function. Using a genetic risk profile score based on the top association from each of the four genome-wide significant regions in our study, the relative risk between the highest and lowest deciles of genetic risk is 2.1

Spontaneous upper limb monoplegia secondary to probable cerebral amyloid angiopathy

Cerebral amyloid angiopathy is a clinicopathological disorder characterised by vascular amyloid deposition initially in leptomeningeal and neocortical vessels, and later affecting cortical and subcortical regions. The presence of amyloid within the walls of these vessels leads to a propensity for primary intracerebral haemorrhage. We report the unusual case of a 77-year-old female who presented to our emergency department with sudden onset isolated hypoaesthesia and right upper limb monoplegia. A CT scan demonstrated a peripheral acute haematoma involving the left perirolandic cortices. Subsequent magnetic resonance imaging demonstrated previous superficial haemorrhagic events. One week following discharge the patient re-attended with multiple short-lived episodes of aphasia and jerking of the right upper limb. Further imaging demonstrated oedematous changes around the previous haemorrhagic insult. Cerebral amyloid angiopathy is an overlooked cause of intracerebral haemorrhage; the isolated nature of the neurological deficit in this case illustrates the many guises in which it can present

Analysis of electrodeposited CdTe thin films grown using cadmium chloride precursor for applications in solar cells

Deposition of cadmium telluride (CdTe) from cadmium chloride (CdCl2) and tellurium oxide has been achieved by electroplating technique using two-electrode configuration. Cyclic voltammetry shows that near-stoichiometric CdTe is achievable between 1330 and 1400 mV deposition voltage range. The layers grown were characterised using X-ray diffraction (XRD), UV–Visible spectrophotometry, scanning electron microscopy (SEM), energy-dispersive X-ray analysis (EDX), photoelectrochemical (PEC) cell and DC conductivity measurements. The XRD shows that the electrodeposited CdTe layer is polycrystalline in nature. The UV–Visible spectrophotometry shows that the bandgap of both as-deposited and heat-treated CdTe films are in the range of (1.44–1.46) eV. The SEM shows grain growth after CdCl2 treatment, while, the EDX shows the effect of growth voltage on the atomic composition of CdTe layers. The PEC results show that both p- and n-type CdTe can be electrodeposited and the DC conductivity reveals that the high resistivity is at the inversion growth voltage (Vi) for the as-deposited and CdCl2 treated layers

Collection of Aerosolized Human Cytokines Using Teflon® Filters

Background: Collection of exhaled breath samples for the analysis of inflammatory biomarkers is an important area of research aimed at improving our ability to diagnose, treat and understand the mechanisms of chronic pulmonary disease. Current collection methods based on condensation of water vapor from exhaled breath yield biomarker levels at or near the detection limits of immunoassays contributing to problems with reproducibility and validity of biomarker measurements. In this study, we compare the collection efficiency of two aerosol-to-liquid sampling devices to a filter-based collection method for recovery of dilute laboratory generated aerosols of human cytokines so as to identify potential alternatives to exhaled breath condensate collection. Methodology/Principal Findings: Two aerosol-to-liquid sampling devices, the SKC® Biosampler and Omni 3000™, as well as Teflon® filters were used to collect aerosols of human cytokines generated using a HEART nebulizer and single-pass aerosol chamber setup in order to compare the collection efficiencies of these sampling methods. Additionally, methods for the use of Teflon® filters to collect and measure cytokines recovered from aerosols were developed and evaluated through use of a high-sensitivity multiplex immunoassay. Our results show successful collection of cytokines from pg/m3 aerosol concentrations using Teflon® filters and measurement of cytokine levels in the sub-picogram/mL concentration range using a multiplex immunoassay with sampling times less than 30 minutes. Significant degradation of cytokines was observed due to storage of cytokines in concentrated filter extract solutions as compared to storage of dry filters. Conclusions: Use of filter collection methods resulted in significantly higher efficiency of collection than the two aerosol-to-liquid samplers evaluated in our study. The results of this study provide the foundation for a potential new technique to evaluate biomarkers of inflammation in exhaled breath samples

Improvement of composition of CdTe thin films during heat treatment in the presence of CdCl2

CdCl2 treatment is a crucial step in development of CdS/CdTe solar cells. Although this rocessing step has been used over a period of three decades, full understanding is not yet achieved. This paper reports the experimental evidence for improvement of composition of CdTe layers during CdCl2 treatment. This investigation makes use of four selected analytical techniques; Photo-electro-chemical (PEC) cell, X-ray diffraction (XRD), Raman spectroscopy and Scanning electron microscopy (SEM). CdTe layers used were electroplated using three Cd precursors; CdSO4, Cd(NO3)2 and CdCl2. Results show the improvement of stoichiometry of CdTe layers during CdCl2 treatment through chemical reaction between Cd from CdCl2 and elemental Te that usually precipitate during CdTe growth, due to its natural behaviour. XRD and SEM results show that the low-temperature (~85ºC) electroplated CdTe layers consist of ~(20-60) nm size crystallites, but after CdCl2 treatment, the layers show drastic recrystallisation with grains becoming a few microns in size. These CdCl2 treated layers are then comparable to high temperature grown CdTe layers by the size of grains

Depletion of Trypanosome CTR9 Leads to Gene Expression Defects

The Paf complex of Opisthokonts and plants contains at least five subunits: Paf1, Cdc73, Rtf1, Ctr9, and Leo1. Mutations in, or loss of Paf complex subunits have been shown to cause defects in histone modification, mRNA polyadenylation, and transcription by RNA polymerase I and RNA polymerase II. We here investigated trypanosome CTR9, which is essential for trypanosome survival. The results of tandem affinity purification suggested that trypanosome CTR9 associates with homologues of Leo1 and Cdc73; genes encoding homologues of Rtf1 and Paf1 were not found. RNAi targeting CTR9 resulted in at least ten-fold decreases in 131 essential mRNAs: they included several that are required for gene expression and its control, such as those encoding subunits of RNA polymerases, exoribonucleases that target mRNA, RNA helicases and RNA-binding proteins. Simultaneously, some genes from regions subject to chromatin silencing were derepressed, possibly as a secondary effect of the loss of two proteins that are required for silencing, ISWI and NLP1

Host resistance stability to downy mildew in pearl millet and pathogenic variability in Sclerospora graminicola

Downy mildew, caused by Sclerospora graminicola, is a major pathogen of pearl millet (Pennisetum glaucum) in Asia and Africa. So development of resistant cultivars has been a major goal of national and international breeding programs. Stability of resistance in pearl millet lines developed at ICRISAT was studied through a collaborative International Pearl Millet Downy Mildew Virulence Nursery (IPMDMVN). The reactions to downy mildew of 11 pearl millet lines at 17 locations in India, Burkina Faso, Mali, Niger, and Nigeria from 1995 to 1999 were recorded. Disease incidence varied significantly among lines, locations, and years. The tested pearl millet lines exhibited significant differential resistance. Resistance in lines IP 18292, IP 18293, 700651 and P 310-17 was most stable regardless of the location or season. Analysis of the variation in resistance also suggested that the resistance in IP 18292 and IP 18293 was variable and depended on the locations and years, while the resistance in 700651 and P 310-17 was highly stable across locations and over years. The latter two lines could prove to be the most valuable sources of downy mildew resistance. The results also revealed significant differences in S. graminicola populations at different locations, with the highest disease at Bagauda (Nigeria) and Durgapura (India) and lowest from Coimbatore and Aurangabad (India). Based on the reaction of the 11 pearl millet lines, the 17 S. graminicola populations were grouped into six putative pathotypes (undefined populations closer to races)