Pattern of cutaneous adverse drug reactions at a tertiary care hospital in southern India

Background: The objective of the study was to assess the pattern of cutaneous adverse drug reactions reported by active surveillance to the Pharmacovigilance center of a tertiary care hospital in southern india, and also to establish the drugs causing the same and observe the age wise and gender based incidence of such reactions.Methods: The cutaneous ADRs (CADRs) reported to the Pharmacovigilance center of the institution were analysed retrospectively during the period of March 2013 to December 2015. The various pattern of skin reactions and the most frequent drugs causing the same were established. An age wise and gender based incidence of CADRs and drugs causing them were also reported.Results: A total of 293 cases were taken for analysis. The male female ratio was 0.89-1.in our study. Among the age wise distribution of CADRs, 57(19.4%) were seen in paediatric, 194(66.2%) in adults and 33(11.2%) in geriatric age groups. The most frequent drugs to cause the CADRs were antimicrobials 183(62.4%) followed by NSAIDs 38(12.9%) and antacids 17(5.8%).Among the skin reactions urticaria/ angioedema was the most common 109(37.2%) followed by generalised pruritis 57(19.5%) and fixed drug eruption 37(12.6%). In all the age groups and both the sexes urticaria/angioedema and generalised pruritis were the leading skin reactions observed.Conclusions: As CADRs are the most common ADRs among others, it is prudent to monitor them closely, as any change in pattern with older or newer agents can alert the health care personnel in instituting the appropriate prescription patterns, which can overall impact the quality of health care positively

Outpatient prescription audit in a tertiary care hospital at Puducherry

Background: Rational use of medicines promotes good health practices and prevents inappropriate use of medicines, polypharmacy, unnecessary use of antimicrobials, injections, and also encourages use of medicines from essential medicine list and dispensing by generic names. The aim of the study was to analyze the outpatient prescriptions of a tertiary care centre by utilizing World Health Organization (WHO) core drug use prescribing indicators.Methods: A retrospective observational study was conducted in a tertiary care health setup at Puducherry, South India. Outpatient prescriptions from all the major clinical departments were analyzed using WHO prescribing indicators and they were compared with some similar studies.Results: The average number of drugs per prescription was 2.74. The percentage of prescriptions with antibiotics was 20.33% and the percentage of prescriptions with injections was 0.16%. The percentage of drugs prescribed by generic names and from essential medicine list was 83.13% and 87.9 respectively. Further antibiotic utilization was found to be higher in the department of ENT (56.67%), respiratory medicine (45%) and surgery (40%). Percentage of drugs prescribed by generic names in pediatrics and respiratory medicine were found to be 67.88% and 65.27% and percentage of drugs prescribed from essential medicine list in dermatology was 69.62%.Conclusions: Prescription pattern followed in our Institute almost adheres to the guidelines laid down by the WHO. Moreover, it is also implied that a routine audit of this type should be done in health care setups to ensure that they adhere to the WHO guidelines for better health care

Observations of the 6 Centimeter Lines of OH in Evolved (OH/IR) Stars

Recent observational and theoretical advances have called into question traditional OH maser pumping models in evolved (OH/IR) stars. The detection of excited-state OH lines would provide additional constraints to discriminate amongst these theoretical models. In this Letter, we report on VLA observations of the 4750 MHz and 4765 MHz lines of OH toward 45 sources, mostly evolved stars. We detect 4765 MHz emission in the star forming regions Mon R2 and LDN 1084, but we do not detect excited-state emission in any evolved stars. The flux density and velocity of the 4765 MHz detection in Mon R2 suggests that a new flaring event has begun.Comment: 4 pages, to appear in ApJ

HI in circumstellar environments

We present new results of a spectroscopic survey of circumstellar HI in the direction of evolved stars made with the Nancay Radiotelescope. The HI line at 21 cm has been detected in the circumstellar shells of a variety of evolved stars: AGB stars, oxygen-rich and carbon-rich, Semi-Regular and Miras, and Planetary Nebulae. The emissions are generally spatially resolved, i.e. larger than 4', indicating shell sizes of the order of 1 pc which opens the possibility to trace the history of mass loss over the past ~ 10^4-10^5 years. The line-profiles are sometimes composite. The individual components have generally a quasi-Gaussian shape; in particular they seldom show the double-horn profile that would be expected from the spatially resolved optically thin emission of a uniformly expanding shell. This probably implies that the expansion velocity decreases outwards in the external shells (0.1-1 pc) of these evolved stars. The HI line-profiles do not necessarily match those of the CO rotational lines. Furthermore, the centroid velocities do not always agree with those measured in the CO lines and/or the stellar radial velocities. The HI emissions may also be shifted in position with respect to the central stars. Without excluding the possibility of asymmetric mass ejection, we suggest that these two effects could also be related to a non-isotropic interaction with the local interstellar medium. HI was detected in emission towards several sources (rho Per, alpha Her, delta^2 Lyr, U CMi) that otherwise have not been detected in any radio lines. Conversely it was not detected in the two oxygen-rich stars with substantial mass-loss rate, NML Tau and WX Psc, possibly because these sources are young with hydrogen in molecular form, and/or because the temperature of the circumstellar HI gas is very low (< 5 K).Comment: Accepted for publication in The Astronomical Journa

Abnormal Placental Development and Early Embryonic Lethality in EpCAM-Null Mice

BACKGROUND: EpCAM (CD326) is encoded by the tacstd1 gene and expressed by a variety of normal and malignant epithelial cells and some leukocytes. Results of previous in vitro experiments suggested that EpCAM is an intercellular adhesion molecule. EpCAM has been extensively studied as a potential tumor marker and immunotherapy target, and more recent studies suggest that EpCAM expression may be characteristic of cancer stem cells. METHODOLOGY/PRINCIPAL FINDINGS: To gain insights into EpCAM function in vivo, we generated EpCAM -/- mice utilizing an embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2 exons of the tacstd1 gene fused in frame to betageo. EpCAM +/- mice were viable and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/- embryos revealed that betageo was expressed in several epithelial structures including developing ears (otocysts), eyes, branchial arches, gut, apical ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM -/- mice died in utero by E12.5, and were small, developmentally delayed, and displayed prominent placental abnormalities. In developing placentas, EpCAM was expressed throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas of EpCAM -/- embryos were compact, with thin labyrinthine layers lacking prominent vascularity. Parietal trophoblast giant cells were also dramatically reduced in EpCAM -/- placentas. CONCLUSION: EpCAM was required for differentiation or survival of parietal trophoblast giant cells, normal development of the placental labyrinth and establishment of a competent maternal-fetal circulation. The findings in EpCAM-reporter mice suggest involvement of this molecule in development of vital organs including the gut, kidneys, pancreas, lungs, eyes, and limbs

Quantitative proteomic analysis of the influence of lignin on biofuel production by Clostridium acetobutylicum ATCC 824

Background: Clostridium acetobutylicum has been a focus of research because of its ability to produce high-value compounds that can be used as biofuels. Lignocellulose is a promising feedstock, but the lignin–cellulose–hemicellulose biomass complex requires chemical pre-treatment to yield fermentable saccharides, including cellulose-derived cellobiose, prior to bioproduction of acetone–butanol–ethanol (ABE) and hydrogen. Fermentation capability is limited by lignin and thus process optimization requires knowledge of lignin inhibition. The effects of lignin on cellular metabolism were evaluated for C. acetobutylicum grown on medium containing either cellobiose only or cellobiose plus lignin. Microscopy, gas chromatography and 8-plex iTRAQ-based quantitative proteomic technologies were applied to interrogate the effect of lignin on cellular morphology, fermentation and the proteome. Results: Our results demonstrate that C. acetobutylicum has reduced performance for solvent production when lignin is present in the medium. Medium supplemented with 1 g L−1 of lignin led to delay and decreased solvents production (ethanol; 0.47 g L−1 for cellobiose and 0.27 g L−1 for cellobiose plus lignin and butanol; 0.13 g L−1 for cellobiose and 0.04 g L−1 for cellobiose plus lignin) at 20 and 48 h, respectively, resulting in the accumulation of acetic acid and butyric acid. Of 583 identified proteins (FDR < 1 %), 328 proteins were quantified with at least two unique peptides. Up- or down-regulation of protein expression was determined by comparison of exponential and stationary phases of cellobiose in the presence and absence of lignin. Of relevance, glycolysis and fermentative pathways were mostly down-regulated, during exponential and stationary growth phases in presence of lignin. Moreover, proteins involved in DNA repair, transcription/translation and GTP/ATP-dependent activities were also significantly affected and these changes were associated with altered cell morphology. Conclusions: This is the first comprehensive analysis of the cellular responses of C. acetobutylicum to lignin at metabolic and physiological levels. These data will enable targeted metabolic engineering strategies to optimize biofuel production from biomass by overcoming limitations imposed by the presence of lignin

Magnetic Particle-Scanning for Ultrasensitive Immunodetection On-Chip

We describe the concept of magnetic particle-scanning for on-chip detection of biomolecules: a magnetic particle, carrying a low number of antigens (Ag's) (down to a single molecule), is transported by hydrodynamic forces and is subjected to successive stochastic reorientations in an engineered magnetic energy landscape. The latter consists of a pattern of substrate-bound small magnetic particles that are functionalized with antibodies (Ab's). Subsequationuent counting of the captured Ag-carrying particles provides the detection signal. The magnetic particle-scanning principle is investigated in a custom-built magneto-microfluidic chip and theoretically described by a random walk-based model, in which the trajectory of the contact point between an Ag-carrying particle and the small magnetic particle pattern is described by stochastic moves over the surface of the mobile particle, until this point coincides with the position of an Ag, resulting in the binding of the particle. This model explains the particular behavior of previously reported experimental dose-response curves obtained for two different ligand-receptor systems (biotin/streptavidin and TNF-alpha) over a wide range of concentrations. Our model shows that magnetic particle-scanning results in a very high probability of irrununocomplex formation for very low Ag concentrations, leading to an extremely low limit of detection, down to the single molecule-per-particle level. When compared to other types of magnetic particle-based surface coverage assays, our strategy was found to offer a wider dynamic range (>8 orders of magnitude), as the system does not saturate for concentrations as high as 10(11) Ag molecules in a 5 mu L drop. Furthermore, by emphasizing the importance of maximizing the encounter probability between the Ag and the Ab to improve sensitivity, our model also contributes to explaining the behavior of other particle-based heterogeneous immunoassays

Intracellular protein determination using droplet-based immunoassays

This paper describes the implementation of a sensitive, on-chip immunoassay for the analysis of intracellular proteins, developed using microdroplet technology. The system offers a number of analytical functionalities, enabling the lysis of low cell numbers, as well as protein detection and quantification, integrated within a single process flow. Cells were introduced into the device in suspension and were electrically lysed in situ. The cell lysate was subsequently encapsulated together with antibody-functionalized beads into stable, water-in-oil droplets, which were stored on-chip. The binding of intracellular proteins to the beads was monitored fluorescently. By analyzing many individual droplets and quantifying the data obtained against standard additions, we measured the level of two intracellular proteins, namely, HRas-mCitrine, expressed within HEK-293 cells, and actin-EGFP, expressed within MCF-7 cells. We determined the concentrations of these proteins over 5 orders of magnitude, from 50 pM to 1 μM. The results from this semiautomated method were compared to those for determinations made using Western blots, and were found not only to be faster, but required a smaller number of cells