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1.  Synergistic effects of NOD1 or NOD2 and TLR4 activation on mouse sickness behavior in relation to immune and brain activity markers☆ 
Brain, Behavior, and Immunity  2015;44:106-120.
Toll-like receptors (TLRs) and nuclear-binding domain (NOD)-like receptors (NLRs) are sensors of bacterial cell wall components to trigger an immune response. The TLR4 agonist lipopolysaccharide (LPS) is a strong immune activator leading to sickness and depressed mood. NOD agonists are less active but can prime immune cells to augment LPS-induced cytokine production. Since the impact of NOD and TLR co-activation in vivo has been little studied, the effects of the NOD1 agonist FK565 and the NOD2 agonist muramyl dipeptide (MDP), alone and in combination with LPS, on immune activation, brain function and sickness behavior were investigated in male C57BL/6N mice.
Intraperitoneal injection of FK565 (0.001 or 0.003 mg/kg) or MDP (1 or 3 mg/kg) 4 h before LPS (0.1 or 0.83 mg/kg) significantly aggravated and prolonged the LPS-evoked sickness behavior as deduced from a decrease in locomotion, exploration, food intake and temperature. When given alone, FK565 and MDP had only minor effects. The exacerbation of sickness behavior induced by FK565 or MDP in combination with LPS was paralleled by enhanced plasma protein and cerebral mRNA levels of proinflammatory cytokines (IFN-γ, IL-1β, IL-6, TNF-α) as well as enhanced plasma levels of kynurenine. Immunohistochemical visualization of c-Fos in the brain revealed that NOD2 synergism with TLR4 resulted in increased activation of cerebral nuclei relevant to sickness.
These data show that NOD1 or NOD2 synergizes with TLR4 in exacerbating the immune, sickness and brain responses to peripheral immune stimulation.
Our findings demonstrate that the known interactions of NLRs and TLRs at the immune cell level extend to interactions affecting brain function and behavior.
doi:10.1016/j.bbi.2014.08.011
PMCID: PMC4295938  PMID: 25218901
Anxiety; c-Fos; Corticosterone; FK565; Food intake; Kynurenine; Lipopolysaccharide; Locomotion; Muramyl dipeptide; Proinflammatory cytokines
2.  Atypical Neurocytoma: Dilemma in diagnosis and management 
Background:
Central neurocytoma is an uncommon benign tumor of the central nervous system. A section of these tumors have unusual aggressiveness and are termed as “atypical central neurocytomas,” the definition of which is debated. Many studies in the available literature define them as tumors with elevated MIB-1 labeling index (MIB-1 LI) >2%, while some associate them with higher values of MIB-1 LI or those with histological atypical features. Newer parameters also have been identified and correlated with MIB-1 LI to differentiate atypical from benign neurocytoma cases. A recent analysis of the atypical neurocytoma cases with malignant behavior revealed their increased tendency of spread through the cerebrospinal fluid causing craniospinal axis dissemination. However, limited studies document the appropriate indications and usefulness of additional therapeutic modalities, such as upfront craniospinal irradiation (CSI) or adjuvant chemotherapy, in countering the aggressive behavior of such tumors.
Case Description:
We present two such rare cases of atypical neurocytoma with elevated MIB-1 LI, of 3% and 4%, respectively, without histological atypia. Since there is insufficient evidence documenting advantages of any additional measures in the adjuvant management of atypical cases, both patients were treated with localized cranial radiotherapy alone, as per the evidence available in the literature currently.
Conclusion:
We propose that future studies must aptly redefine these atypical neurocytomas with malignant potential and provide guidance to identify aggressiveness of these tumors early in the course of management. Lastly, strong evidence to provide specific adjuvant therapy is also warranted.
doi:10.4103/2152-7806.147414
PMCID: PMC4287918  PMID: 25593767
Atypical neurocytoma; cerebrospinal fluid dissemination; chemotherapy; craniospinal irradiation; malignant; MIB labeling index; radiotherapy
3.  Study of General Awareness, Attitude, Behavior, and Practice Study on Dog Bites and its Management in the Context of Prevention of Rabies Among the Victims of Dog Bite Attending the OPD Services of CHC Muradnagar 
Objectives:
This is a recent study conducted during 15th September 2013 to 15th December 2013 at the community health centre (CHC), Muradnagar, distt Ghaziabad, among the victims of dog/animal bite attending the daily OPD services of CHC. To identify the level of general awareness and knowledge of wound management and rabies among the cases of dog bite and to study the awareness of people about antirabies vaccines and health service utilization.
Methods:
The study population composed of 250 victims of dog or animal bite, Patients were selected and approached after proper briefing, with well-prepared two page structured questionnaire designed in local language to assess their knowledge about the wound management, information about the epidemiology of dog bite.
Results and conclusion:
The result of the study reflect the very low level of awareness about the postdog bite management of wounds as well as about the disease rabies group of people questioned and also reveals serious gaps in understanding of wound severity, classification and correct application of PEP with ARV vaccine and RIG. There is definitely a gap in people's knowledge, attitude, and practices about dog bite and its management and there is need of taking serious measures for the control of stray dog population at the block level.
doi:10.4103/2249-4863.148107
PMCID: PMC4311341  PMID: 25657942
Attitude; dog bite; rabies; knowledge
4.  Repeated predictable stress causes resilience against colitis-induced behavioral changes in mice 
Inflammatory bowel disease is associated with an increased risk of mental disorders and can be exacerbated by stress. In this study which was performed with male 10-week old C57Bl/6N mice, we used dextran sulfate sodium (DSS)-induced colitis to evaluate behavioral changes caused by intestinal inflammation, to assess the interaction between repeated psychological stress (water avoidance stress, WAS) and colitis in modifying behavior, and to analyze neurochemical correlates of this interaction. A 7-day treatment with DSS (2% in drinking water) decreased locomotion and enhanced anxiety-like behavior in the open field test and reduced social interaction. Repeated exposure to WAS for 7 days had little influence on behavior but prevented the DSS-induced behavioral disturbances in the open field and SI tests. In contrast, repeated WAS did not modify colon length, colonic myeloperoxidase content and circulating proinflammatory cytokines, parameters used to assess colitis severity. DSS-induced colitis was associated with an increase in circulating neuropeptide Y (NPY), a rise in the hypothalamic expression of cyclooxygenase-2 mRNA and a decrease in the hippocampal expression of NPY mRNA, brain-derived neurotrophic factor mRNA and mineralocorticoid receptor mRNA. Repeated WAS significantly decreased the relative expression of corticotropin-releasing factor mRNA in the hippocampus. The effect of repeated WAS to blunt the DSS-evoked behavioral disturbances was associated with a rise of circulating corticosterone and an increase in the expression of hypothalamic NPY mRNA. These results show that experimental colitis leads to a particular range of behavioral alterations which can be prevented by repeated WAS, a model of predictable chronic stress, while the severity of colitis remains unabated. We conclude that the mechanisms underlying the resilience effect of repeated WAS involves hypothalamic NPY and the hypothalamic-pituitary-adrenal axis.
doi:10.3389/fnbeh.2014.00386
PMCID: PMC4222228  PMID: 25414650
DSS-induced colitis; resilience; anxiety; social interaction; cyclooxygenase 2; neuropeptide Y; corticosterone; gut-brain axis
6.  LIPITENSION: Interplay between dyslipidemia and hypertension 
The burden of cardiovascular disease (CVD) is increasing worldwide. The increase in the burden is a major concern in developing countries like India. It is well-established that hypertension and dyslipidemia are the two major contributing risk factors for CVD. Various epidemiological studies have shown the prevalence of the co-existence of hypertension and dyslipidemia, in the range of 15 to 31%. The co-existence of the two risk factors has more than an additive adverse impact on the vascular endothelium, which results in enhanced atherosclerosis, leading to CVD. This review emphasizes on the ‘co-existence and interplay of dyslipidemia and hypertension’. The authors have termed the co-existence as, ‘LIPITENSION’. The term LIPITENSION may help clinicians in easy identification and aggressive management of the two conditions together, ultimately preventing future cardiovascular events.
doi:10.4103/2230-8210.93742
PMCID: PMC3313742  PMID: 22470861
Cardiovascular risk factors; dyslipidemia; hypertension; lipitension
7.  Common Genetic Variation Near Melatonin Receptor MTNR1B Contributes to Raised Plasma Glucose and Increased Risk of Type 2 Diabetes Among Indian Asians and European Caucasians 
Diabetes  2009;58(11):2703-2708.
OBJECTIVE
Fasting plasma glucose and risk of type 2 diabetes are higher among Indian Asians than among European and North American Caucasians. Few studies have investigated genetic factors influencing glucose metabolism among Indian Asians.
RESEARCH DESIGN AND METHODS
We carried out genome-wide association studies for fasting glucose in 5,089 nondiabetic Indian Asians genotyped with the Illumina Hap610 BeadChip and 2,385 Indian Asians (698 with type 2 diabetes) genotyped with the Illumina 300 BeadChip. Results were compared with findings in 4,462 European Caucasians.
RESULTS
We identified three single nucleotide polymorphisms (SNPs) associated with glucose among Indian Asians at P < 5 × 10−8, all near melatonin receptor MTNR1B. The most closely associated was rs2166706 (combined P = 2.1 × 10−9), which is in moderate linkage disequilibrium with rs1387153 (r2 = 0.60) and rs10830963 (r2 = 0.45), both previously associated with glucose in European Caucasians. Risk allele frequency and effect sizes for rs2166706 were similar among Indian Asians and European Caucasians: frequency 46.2 versus 45.0%, respectively (P = 0.44); effect 0.05 (95% CI 0.01–0.08) versus 0.05 (0.03–0.07 mmol/l), respectively, higher glucose per allele copy (P = 0.84). SNP rs2166706 was associated with type 2 diabetes in Indian Asians (odds ratio 1.21 [95% CI 1.06–1.38] per copy of risk allele; P = 0.006). SNPs at the GCK, GCKR, and G6PC2 loci were also associated with glucose among Indian Asians. Risk allele frequencies of rs1260326 (GCKR) and rs560887 (G6PC2) were higher among Indian Asians compared with European Caucasians.
CONCLUSIONS
Common genetic variation near MTNR1B influences blood glucose and risk of type 2 diabetes in Indian Asians. Genetic variation at the MTNR1B, GCK, GCKR, and G6PC2 loci may contribute to abnormal glucose metabolism and related metabolic disturbances among Indian Asians.
doi:10.2337/db08-1805
PMCID: PMC2768158  PMID: 19651812
8.  Light-activated RNA interference using double-stranded siRNA precursors modified using a remarkable regiospecificity of diazo-based photolabile groups 
Nucleic Acids Research  2009;37(13):4508-4517.
Diazo-based precursors of photolabile groups have been used extensively for modifying nucleic acids, with the intention of toggling biological processes with light. These processes include transcription, translation and RNA interference. In these cases, the photolabile groups have been typically depicted as modifying the phosphate backbone of RNA and DNA. In this work we find that these diazo-based reagents in fact react very poorly with backbone phosphates. Instead, they show a remarkable specificity for terminal phosphates and very modest modification of the nucleobases. Furthermore, the photo deprotection of these terminal modifications is shown to be much more facile than nucleobase modified sites. In this study we have characterized this regiospecificity using RNA duplexes and model nucleotides, analyzed using LC/MS/MS. We have also applied this understanding of the regio-specificity to our technique of light activated RNA interference (LARI). We examined 27-mer double-stranded precursors of siRNA (‘dsRNA’), and have modified them using the photo-cleavable di-methoxy nitro phenyl ethyl group (DMNPE) group. By incorporating terminal phosphates in the dsRNA, we are able to guide DMNPE to react at these terminal locations. These modified dsRNA duplexes show superior performance to our previously described DMNPE-modified siRNA, with the range of expression that can be toggled by light increasing by a factor of two.
doi:10.1093/nar/gkp415
PMCID: PMC2715251  PMID: 19477960

Results 1-8 (8)