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Tyagi T.,Defense Institute of Physiology and Allied science | Ahmad S.,Institute of Genomics and Integrative Biology | Gupta N.,Defense Institute of Physiology and Allied science | Sahu A.,Defense Institute of Physiology and Allied science | And 8 more authors.
Blood | Year: 2014

Oxygen-compromised environments, such as high altitude, air travel, and sports, and pathological conditions, such as solid tumors, have been suggested to be prothrombotic. Despite the indispensable role of platelets in thrombus formation, the studies linking hypoxia, platelet reactivity, and thrombus formation are limited. In the present study, platelet proteome/reactivity was analyzed to elucidate the acute hypoxia-induced prothrombotic phenotype. Rats exposed to acute simulated hypoxia (282 torr/8% oxygen) demonstrated a decreased bleeding propensity and increased platelet reactivity. Proteomic analysis of hypoxic platelets revealed 27 differentially expressed proteins, including those involved in coagulation. Among these proteins, calpain small subunit 1, a 28-kDa regulatory component for calpain function, was significantly upregulated under hypoxic conditions. Moreover, intraplatelet Ca2+ level and platelet calpain activity were also found to be in accordance with calpain small subunit 1 expression. The inhibition of calpain activity demonstrated reversal of hypoxia-induced platelet hyperreactivity. The prothrombotic role for calpain was further confirmed by an in vivo model of hypoxia-induced thrombosis. Interestingly, patients who developed thrombosis while at extreme altitude had elevated plasma calpain activities and increased soluble P-selectin level. In summary, this study suggests that augmented calpain activity is associated with increased incidence of thrombosis under hypoxic environments. © 2014 by The American Society of Hematology.

Sinha P.,Massachusetts Institute of Technology | Kjelgaard M.M.,Massachusetts Institute of Technology | Kjelgaard M.M.,Massachusetts General Hospital | Gandhi T.K.,Massachusetts Institute of Technology | And 6 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014

A rich collection of empirical findings accumulated over the past three decades attests to the diversity of traits that constitute the autism phenotypes. It is unclear whether subsets of these traits share any underlying causality. This lack of a cohesive conceptualization of the disorder has complicated the search for broadly effective therapies, diagnostic markers, and neural/genetic correlates. In this paper, we describe how theoretical considerations and a review of empirical data lead to the hypothesis that some salient aspects of the autism phenotype may be manifestations of an underlying impairment in predictive abilities. With compromised prediction skills, an individual with autism inhabits a seemingly "magical" world wherein events occur unexpectedly and without cause. Immersion in such a capricious environment can prove overwhelming and compromise one's ability to effectively interact with it. If validated, this hypothesis has the potential of providing unifying insights into multiple aspects of autism, with attendant benefits for improving diagnosis and therapy. © 2014, National Academy of Sciences. All rights reserved.

Mamta,Defense Institute of Physiology and Allied Science | Mehrotra S.,Amity University | Amitabh,Defense Institute of Physiology and Allied Science | Kirar V.,Defense Institute of Physiology and Allied Science | And 4 more authors.
Indian Journal of Experimental Biology | Year: 2015

This study evaluated the phytochemical and antimicrobial activities and also quantified bioactive nucleoside using high performance thin layer chromatography (HPTLC) of five extracts of Indian Himalayan Cordyceps sinensis prepared with different solvents employing accelerated solvent extraction (ASE) technique. The phytochemical potential of these extracts was quantified in terms of total phenolic and total flavonoid content while antioxidant activities were determined by 1,1-diphenyl-2-pycryl-hydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and ferric-reducing antioxidant power (FRAP) assays. Total reducing power (TRP) was determined by converting iron (III) into iron (II) reduction assay. CS50%Alc (15.1+ 0.67mg/g of dry extract) and CS100%Alc (19.3 + 0.33mg/g of dry extract) showed highest phenolic and flavonoid content, respectively while CSAq extract showed maximum antioxidant activity and the highest concentration of the three nucleosides (adenine 12.8±0.49 mg/g, adenosine 0.36±0.28 mg/g and uracil 0.14±0.36 mg/g of dry extract) determined by HPTLC. The evaluation of extracts for antimicrobial activity against gram-negative and gram-positive bacterial strains showed CS25%Alc, CS75%Alc and CS100%Alc extract to be more effective against E. coli, P. aerugenosa and B. subtilis giving 9, 7 and 6.5 mm of zone of inhibition (ZOI) in 93.75, 93.75 and 45 μg concentration, respectively, whereas CSAq extract showed minimal inhibition against these. © 2015, National Institute of Science Communication. All rights reserved.

Jaiswal M.,Indian Institute of Technology Delhi | Dinda A.K.,All India Institute of Medical Sciences | Gupta A.,Defense Institute of Physiology and Allied science | Koul V.,Indian Institute of Technology Delhi
Biomedical Materials | Year: 2010

A biodegradable semi-interpenetrating hydrogel network (semi-IPN) of polyacrylamide and gelatin was prepared using polycaprolactone diacrylate (mol. wt ∼ 640) as a crosslinker. The drug-polymer interaction and IPN formation were investigated by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) and thermal gravimetric analysis (TGA). Scanning electron micrographs of lyophilized matrices revealed porous internal structure with varying pore sizes under equilibrium hydrated conditions, depending upon formulation composition. pH-dependent swelling and degradation was enhanced with increasing gelatin content and decreasing crosslinker concentration (Cs). Compression modulus (CM) (at 20% strain) increased significantly from 23 ± 1.4 to 75 ± 2.7 kPa (p < 0.02) with increasing Cs (from 0.5 to 2.0 mol%), while it decreased from 162 ± 6.4 to 23 ± 1.4 kPa (p < 0.05) with decreasing PAm/G ratio. Cell viability studies by MTT assay showed excellent cytocompatibility of matrices with fibroblast L929 cells. Curcumin, a hydrophobic phytochemical, was loaded by a diffusion method and its release profile was investigated in 4% w/v aqueous BSA solution at 75 rpm (at 37 ± 0.2 °C). Fitting of drug release data in the Korsmeyer-Peppas model suggested sustained release behavior up to 10 days with a combination of diffusion and erosion mechanism (0.5 < n < 1.0; Mt/M ∞ ≤ 0.6). The newly developed porous, biodegradable and elastic semi-IPNs may serve as an ideal matrix for controlled drug release and wound healing applications. The possibilities can be explored for pharmaceutical and tissue engineering applications. © 2010 IOP Publishing Ltd.

Prasad J.,Defense Institute of Physiology and Allied science | Singh M.,National Dairy Research Institute
Animal | Year: 2010

An experiment was carried out on 10 advance pregnant Murrah buffaloes to determine the role of hormones in milk secretion around parturition. Experimental animals were administered with a single injection of bromocryptine, @ 100 μg/kg BW, for 5 days before expected calving, whereas control group buffaloes were injected with placebo injections. Blood samples collected before parturition (-5,-4,-3,-2,-1 days), on day of parturition (day-0) and on day 1, 2, 3, 4, 5, 10 and 15 post partum were analyzed for growth hormone (GH), insulin like growth factor-I (IGF-I) and prolactin (PRL) by radioimmunassay methods. Milk samples were collected daily for 5 days and on day 10 and 15 after parturition. Milk fat, protein, lactose, citric acid, non-esterified fatty acids (NEFAs) and somatic cell counts (SCCs) were determined in milk samples. Bromocryptine treatment significantly (P < 0.01) decreased pre partum PRL and increased GH levels (P < 0.01) on day of parturition in experimental buffaloes without influencing plasma IGF-I level. Milk yield was significantly lower (P < 0.01) in experimental than in control group. Further, effect of bromocryptine on milk yield was only for a week. Milk yield increased (P < 0.01) gradually and was similar to control group on day 15 post partum. Bromocryptine treatment significantly increased milk SCC (P < 0.01) and protein content (P < 0.01) but there was no effect of treatment on fat, lactose, citric acid, glucose, milk and plasma NEFA concentration. It was concluded that prepartum suppression of PRL by bromocryptine impairs milk secretion temporarily in ensuing lactation. The significant rise in GH level before parturition and on day of parturition suggests a role of it in milk secretion of buffaloes. © 2010 The Animal Consortium.

Prasad J.,Defense Institute of Physiology and Allied science | Baitharu I.,Jaypee University of Information Technology | Sharma A.K.,Defense Institute of Physiology and Allied science | Dutta R.,Defense Institute of Physiology and Allied science | And 2 more authors.
High Altitude Medicine and Biology | Year: 2013

Prasad, Jyotsna, Iswar Baitharu, Alpesh Kumar Sharma, Ruma Dutta, Dipti Prasad, and Shashi Bala Singh. Quercetin reverses hypobaric hypoxia-induced hippocampal neurodegeneration and improves memory function in rat. High Alt Med Biol 14:383-394, 2013.-Inadequate oxygen availability at high altitude causes elevated oxidative stress, resulting in hippocampal neurodegeneration and memory impairment. Though oxidative stress is known to be a major cause of neurodegeneration in hypobaric hypoxia, neuroprotective and ameliorative potential of quercetin, a flavonoid with strong antioxidant properties in reversing hypobaric hypoxia-induced memory impairment has not been studied. Four groups of male adult Sprague Dawley rats were exposed to hypobaric hypoxia for 7 days in an animal decompression chamber at an altitude of 7600 meters. Rats were supplemented with quercetin orally by gavage during 7 days of hypoxic exposure. Spatial working memory was assessed by a Morris Water Maze before and after exposure to hypobaric hypoxia. Changes in oxidative stress markers and apoptotic marker caspase 3 expression in hippocampus were assessed. Histological assessment of neurodegeneration was performed by cresyl violet and fluoro Jade B staining. Our results showed that quercetin supplementation during exposure to hypobaric hypoxia decreased reactive oxygen species levels and consequent lipid peroxidation in the hippocampus by elevating antioxidant status and free radical scavenging enzyme system. There was reduction in caspase 3 expression, and decrease in the number of pyknotic and fluoro Jade B-positive neurons in hippocampus after quercetin supplementation during hypoxic exposure. Behavioral studies showed that quercetin reversed the hypobaric hypoxia-induced memory impairment. These findings suggest that quercetin provides neuroprotection to hippocampal neurons during exposure to hypobaric hypoxia through antioxidative and anti-apoptotic mechanisms, and possesses promising therapeutic potential to ameliorate hypoxia-induced memory dysfunction. © 2013 Mary Ann Liebert, Inc.

Diwaker D.,Defense Institute of Physiology and Allied science | Mishra K.P.,Defense Institute of Physiology and Allied science | Ganju L.,Defense Institute of Physiology and Allied science
Acta Virologica | Year: 2013

Protein disulphide isomerase (PDI) family members are predominantly endoplasmic reticulum (ER)-bound chaperonic proteins, which have also been shown to be present on the cell surface. Some of them have been found to be associated with lipid rafts, MHC class I, and cell-signaling molecules such as signal transducer and activator of transcription (STAT) proteins in certain viral infections. Since there is evidence suggesting that PDIs have a role in the virus entry to the cell, they obviously play an important role in virus-host interactions and viral pathogenesis. In this review, we discuss potential roles of PDIs in viral infections, in order to disclose new antiviral therapeutic targets.

Himadri P.,Defense Institute of Physiology and Allied science | Kumari S.S.,Defense Institute of Physiology and Allied science | Chitharanjan M.,Defense Institute of Physiology and Allied science | Dhananjay S.,Defense Institute of Physiology and Allied science
High Altitude Medicine and Biology | Year: 2010

The present study reports the possible role of oxidative stress and inflammation (role of nuclear factor, NFkB) in hypoxia-induced transvascular leakage in brain of rats. The rats were exposed to a simulated altitude of 25,000 ft for different durations: 0, 3, 6, 12, 24, and 48 h. Brain water content, transvascular leakage, oxidative stress, and proinflammatory parameters were studied at different durations of hypoxic exposure. The results revealed that maximum increase in transvascular leakage in brain of rats was observed at 24 h of hypoxic exposure (240.16±1.95 relative fluorescence units (r.f.u)/g tissue) compared with control (100.58±1.79 r.f.u/g tissue). There was a significant increase in reactive oxygen species (ROS) and lipid peroxidation (MDA), with concomitant reduction in antioxidants. Hypoxic exposure resulted in a significant increase in NFkB protein expression levels and in the DNA binding activity in the 24-h hypoxic exposure (p<0.001) compared with control. There was a significant increase in proinflammatory cytokines, with concomitant upregulation of cell adhesion molecules. Simultaneously, to rule out the fact that inflammation causes cerebral edema, the rats were pretreated with curcumin (100mg/kg body weight) 1h prior to 24-h hypoxia. Curcumin pretreatment significantly attenuated the hypoxia-induced cerebral transvascular leakage (p<0.05), with concomitant downregulation in the expression of brain NFκB levels (p<0.001). The present study therefore reveals that inflammation (NFκB) plays a significant role in hypoxia-induced cerebral edema. © 2010 Mary Ann Liebert, Inc.

Mishra K.P.,Defense Institute of Physiology and Allied science | Chanda S.,Defense Institute of Physiology and Allied science | Shukla K.,Defense Institute of Physiology and Allied science | Ganju L.,Defense Institute of Physiology and Allied science
Immunopharmacology and Immunotoxicology | Year: 2010

In the present study we have evaluated the immunopotentiating activity of Rhodiola aqueous extract (RAE) in rats. The efficacy of RAE was determined by using strong antigen tetanus toxoid (TT) and weak antigen Ovalbumin (OVA). The dynamic changes in humoral and cell-mediated immune response were measured. The results indicated that the TT specific immunoglobulin levels were significantly enhanced by RAE and were at par with complete Freund's adjuvant (CFA). The level of OVA induced antibody response was also enhanced by RAE. It was observed that TT and OVA in combination with CFA or RAE could evoke a significant delayed type hypersensitivity (DTH) response, confirming its potential to generate strong cell-mediated immunity (CMI). The anti-inflammatory or immunosuppressive effect of RAE was evaluated in adjuvant-induced arthritis model (AIA). RAE could not suppress the swelling response. Therefore, this study suggests that RAE has adjuvant/immunopotentiating activity in terms of humoral as well as cell-mediated immune response against strong antigen like TT and weak antigen like OVA. © 2010 Informa UK Ltd.

Kaur G.,Defense Institute of Physiology and Allied science | Chitradevi C.,Defense Institute of Physiology and Allied science | Bansal A.,Defense Institute of Physiology and Allied science
Cellular and Molecular Immunology | Year: 2015

Salmonella infection, ranging from mild, self-limiting diarrhea to severe gastrointestinal, septicemic disease and enteric fever, is a global health problem both in humans and animals. Rapid development of microbial drug resistance has led to a need for efficacious and affordable vaccines against Salmonella. Microbial heat shock proteins (HSPs), including HSP60 and HSP70, are the dominant antigens that promote the host immune response. Co-administration of these antigens with cytokines, such as IL-22, which plays an important role in antimicrobial defense, can enhance the immune response and protection against pathogens. Therefore, the aim of the present study was to determine the immunogenicity of rGroEL (Hsp60) of S. Typhi, alone or administered in combination with murine rIL-22, and its protective efficacy against lethal infection with Salmonella, in mice. There was appreciable stimulation of the humoral and cell-mediated immune responses in mice immunized with rGroEL alone. However, co-administration of rGroEL with rIL-22 further boosted the antibody titers (IgG, IgG1 and IgG2a), T-cell proliferative responses and the secretion of both Th1 and Th2 cytokines. Additionally, rGroEL alone accorded 65%-70% protection against lethal challenge with S. Typhi and S. Typhimurium, which increased to 90% when co-administered with rIL-22. © 2015 CSI and USTC.

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