A retrospective analysis of adverse drug reaction reported in a tertiary care hospital

Background: The adverse drug reactions (ADRs) reported to pharmacovigilance centre in tertiary care hospital was analysed to find out the incidence and causality.Methods: This was a retrospective study to analyse the ADR reported at pharmacovigilance centre after ethical clearance from Institutional Ethic Committee (IEC). ADR data were analysed and ADRs were categorized as department-wise, system affected and causative drug. The causality of each ADR was assessed by WHO-UMC scale.Results: The majority of patients who had suffered from ADRs were between 19-64 years of age (94.2%) and male patients (58.6%) were affected more than female (41.4%). Pulmonary medicine department has reported highest number of ADR followed by dermatology department. Skin (46.5%) was most affected system followed by gastrointestinal (30.45%), CNS (21.26%), respiratory (9.0%) and remaining systems. Rifampicin (13.79%) shows the largest numbers of ADR followed by zidovudine (13.21%), nevirapine (12.64%) and diclofenac sodium (8.0%). The maximum ADRs reported were probable (94.8%) followed by possible (5.2%).Conclusions: In conclusion, the skin was most affected system followed by gastrointestinal, central nervous and respiratory system. Rifampicin has caused maximum ADRs followed by zidovudine, nevirapine and diclofenac sodium. The causality analyses showed that majority of ADRs were probable (94.8%) while remaining falls in possible (5.2%) category

Outlooks of Nanotechnology in Organic Farming Management

Technological advances are getting monitored with time, and science suggests nanotechnology as the emerging future. This even holds correct with human food consumption for health benefits, where organic farming is a better solution for the rising population and is even supported by major countries instead of using chemical fertilisers and pesticides. Nanotechnology provides a platform where nanoparticles help in better management for organic farming by using it as nano fertilisers, nanocides, nano biosensors, nano growth promoters, etc. These nanomaterials can be synthesised by three different mechanisms namely; chemical, physical, and biological methods. Since the chemical and physical mode of synthesis does not follow the criteria of organic farming and have their drawbacks. Hence, the biological method, also known as the green synthesis of nanomaterials fulfills the requirement of organic farming and has achieved the attention of researchers. Extracts of plant parts (stems, roots, leaves, flowers and, fruits) and different microbes, including bacteria, fungus, and mycorrhiza can be used as a base material for the synthesis of nanoparticles under green synthesis mode. The vision behind the green synthesis of nanoparticles was to curb the hazardous effects of chemically synthesised nanoparticles. In the present review, green synthesis of major elements of organic farming namely; nano fertilisers, nano-pesticides, and nano growth promoters, their modes of transportation, their advantages, and disadvantages in organic farming are discussed

Mechanical Ventilator for Delivery of 17O2 in Brief Pulses

The 17O nucleus has been used recently by several groups for magnetic resonance (MR) imaging of cerebral metabolism. Inhalational delivery of 17O2 in very brief pulses could, in theory, have significant advantages for determination of the cerebral metabolic rate for oxygen (CMRO2) with MR imaging. Mechanical ventilators, however, are not typically capable of creating step changes in gas concentration at the airway. We designed a ventilator for large animal and human studies that provides mechanical ventilation to a subject inside an MR scanner through 25 feet of small-bore connecting tubing, and tested its capabilities using helium as a surrogate for 17O2. After switching the source gas from oxygen to helium, the 0-90% response time for helium concentration changes at the airway was 2.4 seconds. The capability for creating rapid step changes in gas concentration at the airway in large animal and human studies should facilitate the experimental testing of the delivery 17O2 in brief pulses, and its potential use in imaging CMRO2

Crowding changes appearance systematically in peripheral, amblyopic, and developing vision

Visual crowding is the disruptive effect of clutter on object recognition. Although most prominent in adult peripheral vision, crowding also disrupts foveal vision in typically developing children and those with strabismic amblyopia. Do these crowding effects share the same mechanism? Here we exploit observations that crowded errors in peripheral vision are not random: Target objects appear either averaged with the flankers (assimilation) or replaced by them (substitution). If amblyopic and developmental crowding share the same mechanism, then their errors should be similarly systematic. We tested foveal vision in children aged 3 to 8 years with typical vision or strabismic amblyopia and peripheral vision in typical adults. The perceptual effects of crowding were measured by requiring observers to adjust a reference stimulus to match the perceived orientation of a target “Vac-Man” element. When the target was surrounded by flankers that differed by ± 30°, all three groups (adults and children with typical or amblyopic vision) reported orientations between the target and flankers (assimilation). Errors were reduced with ± 90° differences but primarily matched the flanker orientation (substitution) when they did occur. A population pooling model of crowding successfully simulated this pattern of errors in all three groups. We conclude that the perceptual effects of amblyopic and developing crowding are systematic and resemble the near periphery in adults, suggesting a common underlying mechanism

Ocular myasthenia gravis saccades as a measure of extraocular muscle function

BACKGROUND: It is important to understand the pathophysiology of ocular myasthenia gravis (OMG) to improve treatment. AIM: To use modern video-oculography to characterise saccadic eye movements in patients with OMG, including anti-AChR, anti-MuSK, anti-LRP4, and seronegative OMG. METHODS: In total, 21 patients with OMG and five age-matched healthy control subjects underwent video-oculography. Participants performed a sequence of horizontal saccades (3 minutes each) at ±5°, ± 10°, and ±20°, followed by 3 minutes of saccades directed at randomly presented targets at ±5°, ± 10°, and ±15°. We recorded the direction, amplitude, duration, peak, and average velocity of each saccade for each task for each participant. RESULTS: Saccadic amplitude, duration, and average velocity were all lower in OMG patients than in control subjects (p < 0.021). Saccadic amplitude and velocity decreased over time, but this decrease was similar in OMG patients and control subjects. Fixation drift and ocular disparity tended to be greater in OMG patients than in control subjects. Saccadic intrusions occurred more frequently in OMG patients than in control subjects (p < 0.001). No significant effects of time or group by time on fixation drift or ocular disparity were found. DISCUSSION: Saccadic velocities in OMG patients differed from those in normal control subjects, which suggests that OMG affects fast-twitch fibres, although fast-twitch fibres were still able to generate “twitch” or “quiver” movements in the presence of even severe ophthalmoplegia. Slow-twitch muscle fibres involved in gaze holding were also affected, accounting for increased fixation drift following saccades. Our objective finding of increased fixation drift and a larger number of saccadic intrusions mirror our anecdotal experience of patients with OMG who report significant diplopia despite minimal ophthalmoplegia on examination. Such microsaccades may be a surrogate for compensation of a gaze-holding deficit in MG

Enterohemorrhagic Escherichia coli O157∶H7 Gene Expression Profiling in Response to Growth in the Presence of Host Epithelia

BACKGROUND: The pathogenesis of enterohemorrhagic Escherichia coli (EHEC) O157:H7 infection is attributed to virulence factors encoded on multiple pathogenicity islands. Previous studies have shown that EHEC O157:H7 modulates host cell signal transduction cascades, independent of toxins and rearrangement of the cytoskeleton. However, the virulence factors and mechanisms responsible for EHEC-mediated subversion of signal transduction remain to be determined. Therefore, the purpose of this study was to first identify differentially regulated genes in response to EHEC O157:H7 grown in the presence of epithelial cells, compared to growth in the absence of epithelial cells (that is, growth in minimal essential tissue culture medium alone, minimal essential tissue culture medium in the presence of 5% CO(2), and Penassay broth alone) and, second, to identify EHEC virulence factors responsible for pathogen modulation of host cell signal transduction. METHODOLOGY/PRINCIPAL FINDINGS: Overnight cultures of EHEC O157:H7 were incubated for 6 hr at 37 degrees C in the presence or absence of confluent epithelial (HEp-2) cells. Total RNA was then extracted and used for microarray analyses (Affymetrix E. coli Genome 2.0 gene chips). Relative to bacteria grown in each of the other conditions, EHEC O157:H7 cultured in the presence of cultured epithelial cells displayed a distinct gene-expression profile. A 2.0-fold increase in the expression of 71 genes and a 2.0-fold decrease in expression of 60 other genes were identified in EHEC O157:H7 grown in the presence of epithelial cells, compared to bacteria grown in media alone. CONCLUSION/SIGNIFICANCE: Microarray analyses and gene deletion identified a protease on O-island 50, gene Z1787, as a potential virulence factor responsible for mediating EHEC inhibition of the interferon (IFN)-gamma-Jak1,2-STAT-1 signal transduction cascade. Up-regulated genes provide novel targets for use in developing strategies to interrupt the infectious process

TNF-α-induced E3 ligase, TRIM15 inhibits TNF-α-regulated NF-κB pathway by promoting turnover of K63 linked ubiquitination of TAK1

Ubiquitin E3-ligases are recruited at different steps of TNF-α-induced NF-κB activation; however, their role in temporal regulation of the pathway remains elusive. The study systematically identified TRIMs as potential feedback regulators of the TNF-α-induced NF-κB pathway. We further observed that TRIM15 is “late” response TNF-α-induced gene and inhibits the TNF-α-induced NF-κB pathway in several human cell lines. TRIM15 promotes turnover of K63-linked ubiquitin chains in a PRY/SPRY domain-dependent manner. TRIM15 interacts with TAK1 and inhibits its K63-linked ubiquitination, thus NF-κB activity. Further, TRIM15 interacts with TRIM8 and inhibits cytosolic translocation to antagonize TRIM8 modualted NF-κB. TRIM8 and TRIM15 also show functionally inverse correlation in psoriasis condition. In conclusion, TRIM15 is TNF-α-induced late response gene and inhibits TNF-α induced NF-κB pathway hence a feedback modulator to keep the proinflammatory NF-κB pathway under control

Inflammation of peripheral tissues and injury to peripheral nerves induce diferring effects in the expression of the calcium-sensitive anandamide synthesising enzyme and related molecules in rat primary sensory neuron

Elevation of intracellular Ca 2+ concentration induces the synthesis of N0 arachydonoylethanolamine (anandamide) in a sub0popu lation of primary sensory neurons. N0acylphosphatidylethanolamine phospholipa se D (NAPE0PLD) is the only known enzyme, which synthesises anandamide in a Ca 2+ 0dependent manner. NAPE0 PLD mRNA, as well as anandamide's main targets, the excitatory transient receptor potential vanilloid type 1 ion channel (TRPV1) and the inhibitory cannabinoid type 1 (CB1) receptor and the main anandamide0hydrolysing enzyme fatty acid amide hydrolase (FAAH) are all expressed by sub0populatio ns of nociceptive primary sensory neurons. Thus, NAPE0PLD, TRPV1, the CB1 rec eptor and FAAH could form an autocrine signalling system, which could shape t he activity of a major sub0 population of nociceptive primary sensory neurons, hence contribute to the development of pain. While the expression patterns of TRPV1, the CB1 receptor and FAAH have been comprehensively elucidated, little i s known about NAPE0PLD expression in primary sensory neurons under physiol ogical and pathological conditions. We report that NAPE0PLD is expressed by about a third of primary sensory neurons, the overwhelming majority of which also express nociceptive markers as well as the CB1 receptor, TRPV1 and FAAH . Inflammation of peripheral tissues and injury to peripheral nerves induce diff ering but concerted changes in the expression pattern of NAPE0PLD, the CB1 receptor, T RPV1 and FAAH. Together these data indicate the existence of the anatomical basis for an autocrine signalling system, in a major proportion of nociceptive primar y sensory neurons, and that alterations in that autocrine signalling by periphe ral pathologies could contribute to the development of both inflammatory and neuropathi c pain