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991.
Mickey S. Tivers Ian Handel Adam G. Gow Vicky J. Lipscomb Rajiv Jalan Richard J. Mellanby 《PloS one》2014,9(1)
Hepatic encephalopathy (HE) is an important cause of morbidity and mortality in patients with liver disease. The pathogenesis of he is incompletely understood although ammonia and inflammatory cytokines have been implicated as key mediators. To facilitate further mechanistic understanding of the pathogenesis of HE, a large number of animal models have been developed which often involve the surgical creation of an anastomosis between the hepatic portal vein and the caudal vena cava. One of the most common congenital abnormalities in dogs is a congenital portosystemic shunt (cpss), which closely mimics these surgical experimental models of HE. Dogs with a cPSS often have clinical signs which mimic clinical signs observed in humans with HE. Our hypothesis is that the pathogenesis of HE in dogs with a cPSS is similar to humans with HE. The aim of the study was to measure a range of clinical, haematological and biochemical parameters, which have been linked to the development of HE in humans, in dogs with a cPSS and a known HE grade. One hundred and twenty dogs with a cPSS were included in the study and multiple regression analysis of clinical, haematological and biochemical variables revealed that plasma ammonia concentrations and systemic inflammatory response syndrome scores predicted the presence of HE. Our findings further support the notion that the pathogenesis of canine and human HE share many similarities and indicate that dogs with cPSS may be an informative spontaneous model of human HE. Further investigations on dogs with cPSS may allow studies on HE to be undertaken without creating surgical models of HE thereby allowing the number of large animals used in animal experimentation to be reduced. 相似文献
992.
Erik Volz Verity Hill John T. McCrone Anna Price David Jorgensen Áine O’Toole Joel Southgate Robert Johnson Ben Jackson Fabricia F. Nascimento Sara M. Rey Samuel M. Nicholls Rachel M. Colquhoun Ana da Silva Filipe James Shepherd David J. Pascall Rajiv Shah Natasha Jesudason Thomas R. Connor 《Cell》2021,184(1):64-75.e11
993.
The effect of orciprenaline sulphate on the in vitro production of PGs E and F by guinea pig uterine tissue homogenates has been investigated. Estimations of PGs were carried out using sensitive radioimmunoassay techniques. The results indicate that orciprenaline can effectively reduce the in vitro yield of PGs E and F from guinea pig uterine tissue. This could in turn be due to an inhibitory effect of orciprenaline on PG formation or due to stimulation of PG breakdown by the drug. The implications of these results in relation to premature labour are discussed. 相似文献
994.
995.
Shivali Gupta Charity Smith Sarah Auclair Anahi De Jesus Delgadillo Nisha Jain Garg 《PloS one》2015,10(6)
Trypanosoma cruzi-induced oxidative and inflammatory responses are implicated in chagasic cardiomyopathy. In this study, we examined the therapeutic utility of a subunit vaccine against T. cruzi and determined if glutathione peroxidase (GPx1, antioxidant) protects the heart from chagasic pathogenesis. C57BL/6 mice (wild-type (WT) and GPx1 transgenic (GPxtg) were infected with T. cruzi and at 45 days post-infection (dpi), immunized with TcG2/TcG4 vaccine delivered by a DNA-prime/Protein-boost (D/P) approach. The plasma and tissue-sections were analyzed on 150 dpi for parasite burden, inflammatory and oxidative stress markers, inflammatory infiltrate and fibrosis. WT mice infected with T. cruzi had significantly more blood and tissue parasite burden compared with infected/GPxtg mice (n = 5-8, p<0.01). Therapeutic vaccination provided >15-fold reduction in blood and tissue parasites in both WT and GPxtg mice. The increase in plasma levels of myeloperoxidase (MPO, 24.7%) and nitrite (iNOS activity, 45%) was associated with myocardial increase in oxidant levels (3-4-fold) and non-responsive antioxidant status in chagasic/WT mice; and these responses were not controlled after vaccination (n = 5-7). The GPxtg mice were better equipped than the WT mice in controlling T. cruzi-induced inflammatory and oxidative stress markers. Extensive myocardial and skeletal tissue inflammation noted in chagasic/WT mice, was significantly more compared with chagasic/GPxtg mice (n = 4-6, p<0.05). Vaccination was equally effective in reducing the chronic inflammatory infiltrate in the heart and skeletal tissue of infected WT and GPxtg mice (n = 6, p<0.05). Hypertrophy (increased BNP and ANP mRNA) and fibrosis (increased collagen) of the heart were extensively present in chronically-infected WT and GPxtg mice and notably decreased after therapeutic vaccination. We conclude the therapeutic delivery of D/P vaccine was effective in arresting the chronic parasite persistence and chagasic pathology; and GPx1 over-expression provided additive benefits in reducing the parasite burden, inflammatory/oxidative stress and cardiac remodeling in Chagas disease. 相似文献
996.
P.K. Agrawal G.K. Garg K.G. Gollakota 《Biochemical and biophysical research communications》1976,70(3):979-986
In our previous communication, we had reported the existence of an early and a late aconitase in T, active during 5 and 12 hr age of culture, respectively. This report was based on their partial purification and stability pattern studies. Present investigations deal with their specific separation by DEAE-cellulose column chromatography, polyacrylamide gel electrophoresis and Sephadex G-100 gel column chromatography, both individually and in mixture. On DEAE-cellulose column chromatography, early and late aconitase (EC.4.2.1.3) are eluted at 183 ml (265 mM NaCl concontration) and 160 ml (110 mM NaCl concentration)elution volume indicating former to be more anionic. In contrast to this, on polyacrylamide gel electrophoresis, early aconitase moves slower towards anode as compared to late aconitase, indicating former to be less anionic than later. The discrepancy has been ascribed to the molecular sieving effect of polyacrylamide, since Sephadex G-100 gel column chromatography has suggested the molecular weight of early aconitase (160,000) to be twice that of late aconitase. Our attempts to demonstrate that early aconitase was a dimer could not succeed. 相似文献
997.
Sheenam Garg Tejinder P. Singh Ravinder K. Malik 《Probiotics and antimicrobial proteins》2020,12(2):517-534
The present study investigated the impact of probiotic Lactobacillus reuteri LR6 on the gut and systemic immunity using protein energy malnourished (PEM) m 相似文献
998.
An integrative genomic approach identifies p73 and p63 as activators of miR-200 microRNA family transcription 总被引:1,自引:0,他引:1
999.
Garg AD Krysko DV Vandenabeele P Agostinis P 《Cancer immunology, immunotherapy : CII》2012,61(2):215-221
Surface-exposed HSP70 and calreticulin are damage-associated molecular patterns (DAMPs) crucially involved in modulating the
success of cancer therapy. Photodynamic therapy (PDT) involves the administration of a photosensitising (PTS) agent followed
by visible light-irradiation. The reactive oxygen species that are thus generated directly kill tumours by damaging their
microvasculature and inducing a local inflammatory reaction. PDT with the PTS photofrin is associated with DAMPs exposure,
but the same is not true for other PTSs. Here, we show that when cancer cells are treated with hypericin-based PDT (Hyp-PDT),
they surface-expose both HSP70 and calreticulin (CRT). Induction of CRT exposure was not accompanied by co-exposure of ERp57,
but this did not compromise the ability of the exposed CRT to regulate the phagocytosis of Hyp-PDT-treated cancer cells by
dendritic cells. Interestingly, we found that Hyp-PDT-induced CRT exposure (in contrast to anthracycline-induced CRT exposure)
was independent of the presence of ERp57. Our results indicate that Hyp-PDT is a potential anti-cancer immunogenic modality. 相似文献
1000.
Anna-Kate Fowler Aveline Hewetson Rajiv G. Agrawal Marisela Dagda Raul Dagda Ruin Moaddel Silvia Balbo Mitesh Sanghvi Yukun Chen Ryan J. Hogue Susan E. Bergeson George I. Henderson Inna I. Kruman 《The Journal of biological chemistry》2012,287(52):43533-43542
The brain is one of the major targets of chronic alcohol abuse. Yet the fundamental mechanisms underlying alcohol-mediated brain damage remain unclear. The products of alcohol metabolism cause DNA damage, which in conditions of DNA repair dysfunction leads to genomic instability and neural death. We propose that one-carbon metabolism (OCM) impairment associated with long term chronic ethanol intake is a key factor in ethanol-induced neurotoxicity, because OCM provides cells with DNA precursors for DNA repair and methyl groups for DNA methylation, both critical for genomic stability. Using histological (immunohistochemistry and stereological counting) and biochemical assays, we show that 3-week chronic exposure of adult mice to 5% ethanol (Lieber-Decarli diet) results in increased DNA damage, reduced DNA repair, and neuronal death in the brain. These were concomitant with compromised OCM, as evidenced by elevated homocysteine, a marker of OCM dysfunction. We conclude that OCM dysfunction plays a causal role in alcohol-induced genomic instability in the brain because OCM status determines the alcohol effect on DNA damage/repair and genomic stability. Short ethanol exposure, which did not disturb OCM, also did not affect the response to DNA damage, whereas additional OCM disturbance induced by deficiency in a key OCM enzyme, methylenetetrahydrofolate reductase (MTHFR) in Mthfr+/− mice, exaggerated the ethanol effect on DNA repair. Thus, the impact of long term ethanol exposure on DNA repair and genomic stability in the brain results from OCM dysfunction, and MTHFR mutations such as Mthfr 677C→T, common in human population, may exaggerate the adverse effects of ethanol on the brain. 相似文献