A REVIEW ON TRANSDERMAL DRUG DELIVERY SYSTEM: A NOVEL TOOL FOR IMPROVING BIOAVAILABILITY

Among all the dosages, oral is the best route of administration for its advantages but due to flow of its demerits like poor bioavailability due to first pass metabolism and unpredictable nature of gastrointestinal absorption. Moreover, oral route is cost prohibitive and inconvenient. Transdermal patches are medicated adhesive patches when it was placed on the skin layer it will deliver the drug into the blood stream through skin layer. To overcome the side effects caused by the oral route, drugs given through transdermal are preferred as transdermal patch. By employing sustained release polymers, transdermal patches can be prepared using solvent casting method. Drug excipients compatibility studies are very important to determine whether the excipients are suitable for that drug or not. These compatibility studies are very important to maintain the stability of dosage form. Evaluation studies are very important to determine the accuracy of dosage form at the same time therapeutic action also. Some of the parameters such as weight variation, physical appearance, drug content, moisture uptake, folding, endurance, swelling study and physical appearance, in vitro dissolution studies, ex vivo studies, and in vivo studies were evaluated

UV SPECTROPHOTOMETRIC METHOD DEVELOPMENT AND VALIDATION FOR SIMULTANEOUS ESTIMATION OF ALPRAZOLAM AND MEBEVERINE HYDROCHLORIDE IN BULK DRUG AND PHARMACEUTICAL FORMULATION

A simple, accurate, precise, sensitive, rapid and economical spectrophotometric method was developed and validated for simultaneous estimation of Alprazolam (ALP) and Mebeverine HCl (MBH) in bulk drug and pharmaceutical formulation. The estimation of these drugs was carried out by using 0.1M HCl as a solvent. The wavelength maxima for Alprazolam and Mebeverine HCl were found to be 262.3 nm and 222.5 nm. The linearity range was observed in the concentration range of 3-15 µg/ml for both drugs and regression equation was found to be for ALP 0.0565x+0.0138 and for MBH 0.049x-0.0126. Percentage recoveries for Alprazolam and Mebeverine HCl were found to be 99.84% and 99.47% respectively. % RSD values for Intra-day precision were found to be for ALP 1.18% and for MBH 0.59%. Inter-day precision %RSD values were found to be for ALP 0.94% and for MBH 0.69%. LOD was found to be for ALP 1.42 (µg/ml) and for MBH 2.1542 (µg/ml). LOQ was found to be for ALP 4.3242 (µg/ml) and for MBH 6.5442 (µg/ml). The %Assay of Alprazolam and Mebeverine HCl were found to be 99.20% and 100.02% respectively. Statistical analysis proved that the developed method can be successfully used for simultaneous analysis of Alprazolam and Mebeverne HCl in pure and tablet dosage forms

A simple novel device for air sampling by electrokinetic capture

© The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Microbiome 3 (2015): 79, doi:10.1186/s40168-015-0141-2.A variety of different sampling devices are currently available to acquire air samples for the study of the microbiome of the air. All have a degree of technical complexity that limits deployment. Here, we evaluate the use of a novel device, which has no technical complexity and is easily deployable. An air-cleaning device powered by electrokinetic propulsion has been adapted to provide a universal method for collecting samples of the aerobiome. Plasma-induced charge in aerosol particles causes propulsion to and capture on a counter-electrode. The flow of ions creates net bulk airflow, with no moving parts. A device and electrode assembly have been re-designed from air-cleaning technology to provide an average air flow of 120 lpm. This compares favorably with current air sampling devices based on physical air pumping. Capture efficiency was determined by comparison with a 0.4 μm polycarbonate reference filter, using fluorescent latex particles in a controlled environment chamber. Performance was compared with the same reference filter method in field studies in three different environments. For 23 common fungal species by quantitative polymerase chain reaction (qPCR), there was 100 % sensitivity and apparent specificity of 87 %, with the reference filter taken as “gold standard.” Further, bacterial analysis of 16S RNA by amplicon sequencing showed equivalent community structure captured by the electrokinetic device and the reference filter. Unlike other current air sampling methods, capture of particles is determined by charge and so is not controlled by particle mass. We analyzed particle sizes captured from air, without regard to specific analyte by atomic force microscopy: particles at least as low as 100 nM could be captured from ambient air. This work introduces a very simple plug-and-play device that can sample air at a high-volume flow rate with no moving parts and collect particles down to the sub-micron range. The performance of the device is substantially equivalent to capture by pumping through a filter for microbiome analysis by quantitative PCR and amplicon sequencing.This work was partly supported by Breakout Labs, a program of the Thiel Foundation, and partly from personal funds from Julian Gordon and Prasanthi Gandhi. This work was supported in part by the US Dept. of Energy under Contract DE-AC02-06CH11357

Unilateral hemothorax in a 46 year old South Indian male due to a giant arteriovenous hemodialysis fistula: a case report

In a patient undergoing regular hemodialysis through an arteriovenous fistula access, pleural effusion is a known long term complication. However, a unilateral hemothorax is relatively uncommon. Here we report a 46 year old male, end-stage renal disease patient, on maintenance hemodialysis, who presented with a giant brachiocephalic AV fistula in his left arm and progressive breathlessness. Radiological imaging revealed a left sided pleural effusion. Ultrasound guided aspiration revealed a hemorrhagic pleural fluid. A Doppler study of the fistula revealed a high velocity blood flow through the fistula, thereby establishing the cause of the unilateral hemothorax. Ligation of the fistula resulted in complete resolution of the hemothorax. The other possible causes for hemothorax in a dialysis patient are also discussed in this case report

The oxysterol 27-hydroxycholesterol increases β-amyloid and oxidative stress in retinal pigment epithelial cells

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease (AD) and age-related macular degeneration (AMD) share several pathological features including β-amyloid (Aβ) peptide accumulation, oxidative damage, and cell death. The causes of AD and AMD are not known but several studies suggest disturbances in cholesterol metabolism as a culprit of these diseases. We have recently shown that the cholesterol oxidation metabolite 27-hydroxycholesterol (27-OHC) causes AD-like pathology in human neuroblastoma SH-SY5Y cells and in organotypic hippocampal slices. However, the extent to which and the mechanisms by which 27-OHC may also cause pathological hallmarks related to AMD are ill-defined. In this study, the effects of 27-OHC on AMD-related pathology were determined in ARPE-19 cells. These cells have structural and functional properties relevant to retinal pigmented epithelial cells, a target in the course of AMD.</p> <p>Methods</p> <p>ARPE-19 cells were treated with 0, 10 or 25 μM 27-OHC for 24 hours. Levels of Aβ peptide, mitochondrial and endoplasmic reticulum (ER) stress markers, Ca²⁺homeostasis, glutathione depletion, reactive oxygen species (ROS) generation, inflammation and cell death were assessed using ELISA, Western blot, immunocytochemistry, and specific assays.</p> <p>Results</p> <p>27-OHC dose-dependently increased Aβ peptide production, increased levels of ER stress specific markers caspase 12 and gadd153 (also called CHOP), reduced mitochondrial membrane potential, triggered Ca²⁺dyshomeostasis, increased levels of the nuclear factor κB (NFκB) and heme-oxygenase 1 (HO-1), two proteins activated by oxidative stress. Additionally, 27-OHC caused glutathione depletion, ROS generation, inflammation and apoptotic-mediated cell death.</p> <p>Conclusions</p> <p>The cholesterol metabolite 27-OHC is toxic to RPE cells. The deleterious effects of this oxysterol ranged from Aβ accumulation to oxidative cell damage. Our results suggest that high levels of 27-OHC may represent a common pathogenic factor for both AMD and AD.</p

An aberrant NOTCH2-BCR signaling axis in B cells from patients with chronic GVHD

B-cell receptor (BCR)-activated B cells contribute to pathogenesis in chronic graft-versus-host disease (cGVHD), a condition manifested by both B-cell autoreactivity and immune deficiency. We hypothesized that constitutive BCR activation precluded functional B-cell maturation in cGVHD. To address this, we examined BCR-NOTCH2 synergy because NOTCH has been shown to increase BCR responsiveness in normal mouse B cells. We conducted ex vivo activation and signaling assays of 30 primary samples from hematopoietic stem cell transplantation patients with and without cGVHD. Consistent with a molecular link between pathways, we found that BCR-NOTCH activation significantly increased the proximal BCR adapter protein BLNK. BCR-NOTCH activation also enabled persistent NOTCH2 surface expression, suggesting a positive feedback loop. Specific NOTCH2 blockade eliminated NOTCH-BCR activation and significantly altered NOTCH downstream targets and B-cell maturation/effector molecules. Examination of the molecular underpinnings of this “NOTCH2-BCR axis” in cGVHD revealed imbalanced expression of the transcription factors IRF4 and IRF8, each critical to B-cell differentiation and fate. All-trans retinoic acid (ATRA) increased IRF4 expression, restored the IRF4-to-IRF8 ratio, abrogated BCR-NOTCH hyperactivation, and reduced NOTCH2 expression in cGVHD B cells without compromising viability. ATRA-treated cGVHD B cells had elevated TLR9 and PAX5, but not BLIMP1 (a gene-expression pattern associated with mature follicular B cells) and also attained increased cytosine guanine dinucleotide responsiveness. Together, we reveal a mechanistic link between NOTCH2 activation and robust BCR responses to otherwise suboptimal amounts of surrogate antigen. Our findings suggest that peripheral B cells in cGVHD patients can be pharmacologically directed from hyperactivation toward maturity

ApoB100/LDLR-/- Hypercholesterolaemic Mice as a Model for Mild Cognitive Impairment and Neuronal Damage

Recent clinical findings support the notion that the progressive deterioration of cholesterol homeostasis is a central player in Alzheimer's disease (AD). Epidemiological studies suggest that high midlife plasma total cholesterol levels are associated with an increased risk of AD. This paper reports the plasma cholesterol concentrations, cognitive performance, locomotor activity and neuropathological signs in a murine model (transgenic mice expressing apoB100 but knockout for the LDL receptor [LDLR]) of human familial hypercholesterolaemia (FH). From birth, these animals have markedly elevated LDL-cholesterol and apolipoprotein B100 (apoB100) levels. These transgenic mice were confirmed to have higher plasma cholesterol concentrations than wild-type mice, an effect potentiated by aging. Further, 3-month-old transgenic mice showed cholesterol (total and fractions) concentrations considerably higher than those of 18-month-old wild-type mice. The hypercholesterolaemia of the transgenic mice was associated with a clear locomotor deficit (as determined by rotarod, grip strength and open field testing) and impairment of the episodic-like memory (determined by the integrated memory test). This decline in locomotor activity and cognitive status was associated with neuritic dystrophy and/or the disorganization of the neuronal microtubule network, plus an increase in astrogliosis and lipid peroxidation in the brain regions associated with AD, such as the motor and lateral entorhinal cortex, the amygdaloid basal nucleus, and the hippocampus. Aortic atherosclerotic lesions were positively correlated with age, although potentiated by the transgenic genotype, while cerebral β-amyloidosis was positively correlated with genetic background rather than with age. These findings confirm hypercholesterolaemia as a key biomarker for monitoring mild cognitive impairment, and shows these transgenic mice can be used as a model for cognitive and psycho-motor decline

A common variant near TGFBR3 is associated with primary open angle glaucoma

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution.We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10−33), we observed one SNP showing significant association to POAG (CDC7–TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10−8). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis