Daily rhythm of nociception in rats

BACKGROUND: Many behavioral and physiological variables exhibit daily rhythmicity. Few investigations of the daily rhythmicity in nociception have been conducted, and conflicting results have been obtained. The present study evaluated the daily rhythmicity in nociception in Wistar rats. METHODS: Nociception was investigated by Eddy's hot plate method, tail immersion method, and tail clip method. The latency between the noxious stimulus and the animal's response was recorded as reaction time. Separate groups of rats were tested in 4-hour intervals for 24 hours. RESULTS: There was clear daily variation in response latency. Reaction time was shortest a few hours before lights-on and longest at the light-dark transition. CONCLUSION: Nociception exhibits robust daily rhythmicity in rats. Sensitivity to pain is highest late in the dark phase of the light-dark cycle and lowest at the light-dark transition

Analysis of Organophosphates Intoxication in a Tertiary Care Hospital

ABSTRACT As the mortality rate is found to be high in organophosphorous poisoning, the study was aimed at studying the socio demographic pattern and mode of presentation of organophosphorous (OP) intoxication in Madurai, Southern Tamil Nadu. A prospective study of fifty organophosphorous compound poisoning cases, admitted through the emergency department of Government Rajaji Hospital, Madurai, were evaluated in the study. Treatment outcome was studied and reduction in cholinesterase activity was estimated to confirm the exposure and assess the severity of OP poisoning. Among the 50 cases evaluated,39 (78%) patients were males, 11(22%) were females and the mean age was 35.82 ±1.779 years. Thirty two (64%) percent of cases were illiterate and twenty six (52%) of the patients were in the lower middle socioeconomic status.Mean arrival time to the hospital after poisoning was 2.609 hours. Exposure routes were gastrointestinal in all the patients. The mortality rate was 34% and related to either the ingestion of higher doses or delay in approaching the hospital for emergency management. There was a significant reduction in serum cholinesterase level (2.5120X10 7 ± 1.592 mol/min/mg protein) (P<0.05) after OP poisoning.The extent of depression reflected the severity and was found to be reverted back towards normal upon treatment. Fatal issue is often related to causes of poisoning (suicide vs. non-suicide), delayed hospitalization and delay in diagnosis or an improper management. These findings call for a shift in emphasis in educating the masses towards first-aid care for intoxication and further necessitate the need for strict regulation of their use and adequate medical management monitoring for serum cholinesterase level will help to bring down the mortality rate

Sostdc1 deficiency accelerates fracture healing by promoting the expansion of periosteal mesenchymal stem cells

Loss of Sostdc1, a growth factor paralogous to Sost, causes the formation of ectopic incisors, fused molars, abnormal hair follicles, and resistance to kidney disease. Sostdc1 is expressed in the periosteum, a source of osteoblasts, fibroblasts and mesenchymal progenitor cells, which are critically important for fracture repair. Here, we investigated the role of Sostdc1 in bone metabolism and fracture repair. Mice lacking Sostdc1 (Sostdc1−/−) had a low bone mass phenotype associated with loss of trabecular bone in both lumbar vertebrae and in the appendicular skeleton. In contrast, Sostdc1−/− cortical bone measurements revealed larger bones with higher BMD, suggesting that Sostdc1 exerts differential effects on cortical and trabecular bone. Mid-diaphyseal femoral fractures induced in Sostdc1−/− mice showed that the periosteal population normally positive for Sostdc1 rapidly expands during periosteal thickening and these cells migrate into the fracture callus at 3 days post fracture. Quantitative analysis of mesenchymal stem cell (MSC) and osteoblast populations determined that MSCs express Sostdc1, and that Sostdc1−/− 5 day calluses harbor > 2-fold more MSCs than fractured wildtype controls. Histologically a fraction of Sostdc1-positive cells also expressed nestin and α-smooth muscle actin, suggesting that Sostdc1 marks a population of osteochondral progenitor cells that actively participate in callus formation and bone repair. Elevated numbers of MSCs in D5 calluses resulted in a larger, more vascularized cartilage callus at day 7, and a more rapid turnover of cartilage with significantly more remodeled bone and a thicker cortical shell at 21 days post fracture. These data support accelerated or enhanced bone formation/remodeling of the callus in Sostdc1−/− mice, suggesting that Sostdc1 may promote and maintain mesenchymal stem cell quiescence in the periosteum

Global Gene Expression Analysis of Murine Limb Development

Detailed information about stage-specific changes in gene expression is crucial for understanding the gene regulatory networks underlying development and the various signal transduction pathways contributing to morphogenesis. Here we describe the global gene expression dynamics during early murine limb development, when cartilage, tendons, muscle, joints, vasculature and nerves are specified and the musculoskeletal system of limbs is established. We used whole-genome microarrays to identify genes with differential expression at 5 stages of limb development (E9.5 to 13.5), during fore- and hind-limb patterning. We found that the onset of limb formation is characterized by an up-regulation of transcription factors, which is followed by a massive activation of genes during E10.5 and E11.5 which levels off at later time points. Among the 3520 genes identified as significantly up-regulated in the limb, we find ∼30% to be novel, dramatically expanding the repertoire of candidate genes likely to function in the limb. Hierarchical and stage-specific clustering identified expression profiles that are likely to correlate with functional programs during limb development and further characterization of these transcripts will provide new insights into specific tissue patterning processes. Here, we provide for the first time a comprehensive analysis of developmentally regulated genes during murine limb development, and provide some novel insights into the expression dynamics governing limb morphogenesis

Host lipidome and tuberculosis treatment failure

INTRODUCTION: Host lipids play important roles in tuberculosis (TB) pathogenesis. Whether host lipids at TB treatment initiation (baseline) affect subsequent treatment outcomes has not been well characterised. We used unbiased lipidomics to study the prospective association of host lipids with TB treatment failure. METHODS: A case–control study (n=192), nested within a prospective cohort study, was used to investigate the association of baseline plasma lipids with TB treatment failure among adults with pulmonary TB. Cases (n=46) were defined as TB treatment failure, while controls (n=146) were those without failure. Complex lipids and inflammatory lipid mediators were measured using liquid chromatography mass spectrometry techniques. Adjusted least-square regression was used to assess differences in groups. In addition, machine learning identified lipids with highest area under the curve (AUC) to classify cases and controls. RESULTS: Baseline levels of 32 lipids differed between controls and those with treatment failure after false discovery rate adjustment. Treatment failure was associated with lower baseline levels of cholesteryl esters and oxylipin, and higher baseline levels of ceramides and triglycerides compared to controls. Two cholesteryl ester lipids combined in a unique classifier model provided an AUC of 0.79 (95% CI 0.65–0.93) in the test dataset for prediction of TB treatment failure. CONCLUSIONS: We identified lipids, some with known roles in TB pathogenesis, associated with TB treatment failure. In addition, a lipid signature with prognostic accuracy for TB treatment failure was identified. These lipids could be potential targets for risk-stratification, adjunct therapy and treatment monitoring

Research Paper - Antitumor activity of Indigofera aspalathoides on Ehrlich ascites carcinoma in mice

Objective: To evaluate the antitumor activity of the ethanol extract of Indigofera aspalathoides (EIA) in mice. Material and Methods: The antitumor activity of EIA was evaluated against the Ehrlich ascites carcinoma (EAC) tumor model. The activity was assessed using survival time, peritoneal cell count, hematological studies, solid tumor mass and in vitro cytotoxicity. Results: Oral administration of EIA increased the survival time and normal peritoneal cell count. Hematological parameters, protein and PCV, which were altered by tumor inoculation, were restored. Solid tumor mass was also significantly reduced. EIA was found to be cytotoxic in the in vitro model. Conclusion: EIA possesses significant antitumor activity

Conceptualisation for implementing total productive maintenance throught the ISO 9001:2008 standard-based quality management system

his paper conceptualises the integration of total productive maintenance (TPM) and ISO 9001 certification by contributing a model called TPM 9001:2008. Through this conceptualisation, the eight TPM pillars are amended to the five major clauses of the ISO 9001:2008 standard. To illustrate this conceptualisation, the contents of a sub-clause of the TPM 9001:2008 model are presented, and the rationale behind its designation is appraised

Synthesis, Antiviral and Cytotoxic Activities of 2-(2-Phenyl carboxylic acid)-3-Phenylquinazolin -4(3H)-one Derivatives

A series of novel 2,3-disubstitutedquinazolin-4(3H)-ones have been synthesized by condensation of 2-substituted benzo[1,3]oxazine-4-ones and anthranilic acid. Synthesized compounds were evaluated for in vitro antiviral activity against HIV, HSV and vaccinia viruses. 5-Bromo-2-(6-bromo-4-oxo-2-phenyl-4H-quinazolin-3-yl)-benzoic acid (MBR2) exhibited distinct antiviral activity against Herpes simplex and vaccinia viruses

An Anova-Based Numerical Analysis of WHA Partial Replacement Concrete

In this work, a study exploiting concretes made with a bio-plant using natural waste is presented. The study examined the effects of partial cement substitution with bio-plants on the mechanical characteristics of conventional concretes and assessed the discrepancy between actual and expected elasticity modulus values. The usage of and effects on the modulus of elasticity of the partial replacement of concrete with WHA have been the subject of extensive research. Research was conducted in the area using various water-cement ratios coupled with water hyacinth ash and replacement percentages of cement. One-way analysis of variance (ANOVA) is used as a practical approach to verify normality. The supplied experimental data sets are used to train and evaluate the reliability predicting model. Thus, the study effort provides an overview of the numerical analysis performed using statistical techniques and the examination of the resulting data. The model's dependability is provided by the linear relationship between the Concrete mix% and with & without WHA. The 90C+10%WHA mixture performs better than conventional concrete