Possible Association between Expression of Chemokine Receptor-2 (CCR2) and Amyotrophic Lateral Sclerosis (ALS) Patients of North India

BACKGROUND AND OBJECTIVES: We earlier reported elevated chemokine ligand-2 (CCL2) in Indian amyotrophic lateral sclerosis (ALS) patients. We now analysed chemokine receptor-2 (CCR2), the receptor of CCL2, in these ALS patients. METHODS: Indian sporadic ALS patients (n=50) were included on the basis of El Escorial criteria. Percentage (%) of CCR2 expressing peripheral blood mononuclear cells (PBMCs) was evaluated using Flow Cytometry. Real Time Polymerase Chain Reaction (PCR) was used to quantitate CCR2 mRNA expression in PBMCs. Normal controls (n = 40) were also included for comparison. RESULTS: Flow Cytometry revealed significantly reduced CCR2 expressing PBMCs in the ALS patients. We also found a significant decline in number of CCR2 expressing PBMCs in limb onset ALS when compared to bulbar onset ALS. PBMCs from ALS patients showed substantial down-regulation of CCR2 mRNA. CCR2 mRNA expression was found to be decreased among limb ALS patients as compared to bulbar onset ALS. Further, the count of CCR2+ PBMCs and CCR2 mRNA transcript in PBMCs was significantly lower in severe and moderate ALS as compared to ALS patients with mild impairments. CONCLUSIONS: Downregulation of PBMCs CCR2 may indicate its etio-pathological relevance in ALS pathogenesis. Reduced PBMCs CCR2 may result in decreased infiltration of leukocytes at the site of degeneration as a compensatory response to ALS. CCR2 levels measurements in hematopoietic stem cells and estimation of comparative PBMCs count among ALS, disease controls and normal controls can unveil its direct neuroprotective role. However, the conclusions are restricted by the absence of neurological/non-neurological disease controls in the study

Vascular endothelial growth factor-A (VEGF-A) and chemokine ligand-2 (CCL2) in Amyotrophic Lateral Sclerosis (ALS) patients

Correction to Gupta P K, Prabhakar S, Sharma S, Anand A. Vascular endothelial growth factor-A (VEGF-A) and chemokine ligand-2 (CCL2) in amyotrophic lateral sclerosis (ALS) patients. Journal of Neuroinflammation 8:47

Vascular endothelial growth factor-A and chemokine ligand (CCL2) genes are upregulated in peripheral blood mononuclear cells in Indian amyotrophic lateral sclerosis patients

<p>Abstract</p> <p>Background</p> <p>We have earlier shown that protein levels of vascular endothelial growth factor-A (VEGF-A) and chemokine ligand-2 (CCL2) were elevated in Indian amyotrophic lateral sclerosis (ALS) patients. Here, we report the mRNA levels of VEGF-A and CCL2 in Indian ALS patients since they display extended survival after disease onset.</p> <p>Methods</p> <p>VEGF-A and CCL2 mRNA levels were measured in peripheral blood mononuclear cells (PBMCs) of 50 sporadic Indian ALS patients using Real Time Polymerase Chain Reaction (PCR) and compared with normal controls (n = 50). Their levels were adjusted for possible confounders like cigarette smoking, alcohol and meat consumption.</p> <p>Results</p> <p>VEGF-A and CCL2 mRNA levels were found to be significantly elevated in PBMCs in ALS patients as compared to controls. PBMCs from definite ALS revealed higher VEGF-A mRNA expression as compared to probable and possible ALS. CCL2 mRNA levels were found to be unaltered when definite, probable and possible ALS were compared. PBMCs from patients with respiratory dysfunction showed much higher VEGF-A and CCL2 elevation when compared to patients without respiratory dysfunction. No association of smoking, alcohol and meat consumption with VEGF-A and CCL2 was observed after analyzing the data with univariate and multivariate analysis.</p> <p>Conclusion</p> <p>VEGF-A and CCL2 mRNA upregulation in PBMCs may have a clinico-pathological/etiological/epidemiological association with ALS pathogenesis. The cross-cultural and cross-ethnic investigations of these molecules could determine if they have any role in enhancing the mean survival time unique to Indian ALS patients.</p

Evaluation of hepatoprotective potential of aqueous extract of Withania somnifera in albino rats

Background: Hepatic diseases are a major cause of morbidity and disability of work force throughout the world. The treatment of hepatic diseases with standard drugs poses the risk of toxicity on various organ systems. Withania somnifera, a herbal plant has been claimed to be effective in the treatment of various types of hepatic conditions. The present study was undertaken to explore the hepatoprotective activity of aqueous extract of Withania somnifera (AEWS) in experimentally induced hepatotoxicity in albino rats.Methods: The study was commenced after obtaining approval from institutional animal ethical committee using AEWS leaves in Albino wistar rats (150-200 gm) of either sex. The hepatoprotective activity was evaluated using biochemical examination. The animals were divided into five groups of six animals each. In each experiment, first group was given normal saline (1 ml/kg/day), second group was injected with toxin CCl4 (1 ml/kg) i.p only once to produce hepatotoxicity, third and fourth groups were given Withania somnifera orally (500 mg/kg and 1000 mg/kg) (respectively), as a single dose per orally every morning and fifthgroup was given standard drug Liv-52 (1 mg/kg).Results: Aqueous extract of Withania somnifera leaves in oral dose exhibited significant hepatoprotective effect in all models used in this study.Conclusions: It can be concluded from our study that aqueous extract of Withania somnifera leaves possesses hepatoprotective activity

Ocular doppler imaging: opening a new window in decoding glaucoma

Background: In the aetiopathogenesis of multifactorial glaucoma autoregulation of ocular blood flow plays an important role as failure of autoregulation may lead to progression of disease. Aim of this study to understand this better this study was designed to investigate the quantum of these abnormalities and their likely role in pathogenesis and prognosis of primary open angle glaucoma(POAG).Methods: This is a case control study design which involved 67 POAG patients and 67 matched controls. The parameters assessed includes peak systolic velocity(PSV), end diastolic velocity(EDV) and resistive index(RI) of ophthalmic artery(OA) and central retinal artery(CRA) of patients having POAG with age and sex matched healthy subjects. The data obtained was statistically analysed using IBM SPSS 21.Results: The study showed decreased PSV of 31.7 cm/s vs 42.7 cm/s(p=0.0001) and EDV11.7 cm/s vs 19.8 cm/s(p=0.002) with increased RI 0.63 vs 0.53(p=0.000) in  OA and PSV of 15.2 cm/s vs 21.4 cm/s(p=0.001) and EDV4.7 cm/s vs 11.7 cm/s(p=0.003) with increased RI 0.69 vs 0.45(p=0.000) in CRA in both eyes in POAG patients as compared to healthy controls.Conclusion: The study has shown the promising application of ocular Doppler in evaluating POAG patients. However, more such studies are needed with larger study sample and on follow up basis for better understanding glaucoma hemodynamics and applicability of ocular Doppler in management of glaucoma

Estimation of leakage power and delay in CMOS circuits using parametric variation

SummaryWith the advent of deep-submicron technologies, leakage power dissipation is a major concern for scaling down portable devices that have burst-mode type integrated circuits. In this paper leakage reduction technique HTLCT (High Threshold Leakage Control Transistor) is discussed. Using high threshold transistors at the place of low threshold leakage control transistors, result in more leakage power reduction as compared to LCT (leakage control transistor) technique but at the scarifies of area and delay. Further, analysis of effect of parametric variation on leakage current and propagation delay in CMOS circuits is performed. It is found that the leakage power dissipation increases with increasing temperature, supply voltage and aspect ratio. However, opposite pattern is noticed for the propagation delay. Leakage power dissipation for LCT NAND gate increases up to 14.32%, 6.43% and 36.21% and delay decreases by 22.5%, 42% and 9% for variation of temperature, supply voltage and aspect ratio. Maximum peak of equivalent output noise is obtained as 127.531nV/Sqrt(Hz) at 400mHz

Evaluation of bio-efficacy and compatibility of emamectin benzoate with neem based biopesticide against fruit borers of brinjal and okra

Bio-efficacy and physical compatibility of biorational insecticides, viz. emamectin benzoate and Neem Baan® was investigated against brinjal shoot and fruit borer, Leucinodes orbonalis Guenne and okra shoot and fruit borer, Earias vittella Fab. under field conditions during kharif 2010 and 2011. Both biorationals were found compatible with each other by using jar test and emulsion stability. The results revealed that in both brinjal and okra there was no phytotoxicity observed due to emamectin benzoate with Neem Baan® combination. The lowest per cent fruit infestation was observed in the treatment of emamectin benzoate combined with Neem Baan® @ 7 ml per litre of water, i e 7.36% and 5.39% on number basis and 8.13% and 5.77% on weight basis in brinjal during kharif 2010 and 2011 respectively. Also the highest marketable fruit yield in weight basis was also obtained in the treatment (12.35 tonnes/ ha and 16.89 tonnes/ha) during kharif 2010 and 2011. Similarly, in okra also it recorded lowest fruit infestation (5.92% and 5.59%) and highest marketable yield (1.62 tonnes/ha and 2.19 tonnes/ha) in 2010 and 2011 on weight basis. Further, it was observed that the plant parameters like shoot length and number of flowers recorded significantly higher in the treatment of emamectin benzoate combined with Neem Baan® than untreated control (T8) in both the years. The results indicated that the combination of neem formulation with emamectin benzoate was effective in managing L. orbonalis and E. vitella