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Pathophysiology of cerebral oedema in acute liver failure

World Journal of Gastroenterology 2013年第48期19卷 9240-9255页

作者： teresa r scott Victoria T Kronsten robin D Hughes Debbie L Shawcross Institute of Liver Studies King’s College London School of Medicine at King’s College Hospital King’s College Hospital London SE5 9RS United Kingdom

Cerebral oedema is a devastating consequence of acute liver failure(ALF)and may be associated with the development of intracranial hypertension and *** ALF,some patients may develop cerebral oedema and increased intracranial pressure but progression to lifethreatening intracranial hypertension is less frequent than previously described,complicating less than one third of cases who have proceeded to coma since the advent of improved clinical *** rapid onset of encephalopathy may be dramatic with the development of asterixis,delirium,seizures and *** and vasogenic oedema mechanisms have been implicated with a preponderance of experimental data favouring a cytotoxic *** swelling is the most consistent neuropathological finding in humans with ALF and ammonia plays a definitive role in the development of cytotoxic brain *** mechanism(s)by which ammonia induces astrocyte swelling remains unclear but glutamine accumulation within astrocytes has led to the osmolyte *** evidence also supports an alternate‘Trojan horse’hypothesis,with glutamine as a carrier of ammonia into mitochondria,where its accumulation results in oxidative stress,energy failure and ultimately astrocyte *** a complete breakdown of the blood-brain barrier is not evident in human ALF,increased permeation to water and other small molecules such as ammonia has been demonstrated resulting from subtle alterations in the protein composition of paracellular tight *** present,there is no fully efficacious therapy for cerebral oedema other than liver transplantation and this reflects our incomplete knowledge of the precise mechanisms underlying this process which remain largely unknown.

关键词： Cerebral oedema Acute liver failure Ammonia Hepatic encephalopathy Intracranial pressure Intracranial hypertension Cerebral blood flow

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CD8+T cell metabolic flexibility elicited by CD28-ArS2 axisdriven alternative splicing of PKM supports antitumor immunity

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Cellular & Molecular Immunology 2024年第3期21卷 260-274页

作者： G.Aaron Holling Colin A.Chavel Anand P.Sharda Mackenzie M.Lieberman Caitlin M.James Shivana M.Lightman Jason H.Tong Guanxi Qiao Tiffany r.Emmons Thejaswini Giridharan Shengqi Hou Andrew M.Intlekofer richard M.Higashi teresa W.M.Fan Andrew N.Lane Kevin H.Eng Brahm H.Segal Elizabeth A.repasky Kelvin P.Lee scott H.Olejniczak Department of Immunology Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Department of Medicine Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Center for Environmental Systems Biochemistry Department of Toxicology and Cancer Biology and Markey Cancer CenterLexingtonKY 40536USA Department of Cancer Genetics and Genomics Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Present address:University of Colorado Boulder BoulderCO 80309USA Present address:Dana Farber Cancer Institute BostonMA 02215USA Present address:Massachusetts Institute of Technology BostonMA 02139USA Present address:Melvin and Bren Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202USA

Metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been *** this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ArS2 on mature T *** doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose ***2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mrNAs and affected approximately one-third of T-cell activation-induced alternative splicing *** these effects,the CD28-ArS2 axis suppressed the expression of the M1 isoform of pyruvate kinase in favor of PKM2,a key determinant of CD8+T-cell glucose utilization,interferon gamma production,and antitumor effector ***,PKM alternative splicing occurred independently of CD28-driven PI3K pathway activation,revealing a novel means by which costimulation reprograms glucose metabolism in CD8+T cells.

关键词： Immunometabolism mrNA splicing CD8 T cells ArS2 PKM2

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C-reactive protein is differentially modulated by co-existing infections,vitamin deficiencies and maternal factors in pregnant and lactating indigenous Panamanian women

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Infectious Diseases of Poverty 2017年第1期6卷 819-832页

作者： Doris Gonzalez-Fernandez Emerita del Carmen Pons Delfina rueda Odalis teresa Sinisterra Enrique Murillo Marilyn E.scott Kristine G.Koski School of Dietetics and Human Nutrition Macdonald Campus of McGill University21111 Lakeshore RoadSte-Anne-de-BellevueQC H9X 3V9Canada Department of Nutritional Health Ministry of HealthAnconPanama CityPanama “Comarca Ngabe-Bugle”Health region Ministry of HealthSan FelixChiriqui ProvincePanama “Panama Norte”Health region Ministry of HealthLas Cumbres SquareTransithmian HighwayPanama CityPanama Department of Biochemistry University of PanamaSimon Bolivar Avenue(Transithmian Highway)Panama CityPanama Department of Biochemistry University of PanamaManuel Espinoza Batista and Jose De Fabrega AvenuesPanama CityPanama Institute of Parasitology and Centre for Host-Parasite Interactions Macdonald Campus of McGill University21111 Lakeshore RoadSte-Anne-de-BellevueQC H9X 3 V9Canada School of Dietetics and Human Nutrition and Centre for Host-Parasite Interactions Macdonald CampusMcGill University21111 Lakeshore RoadSte-Anne-de-BellevueQC H9X 3 V9Canada

Background:The usefulness of C-reactive protein(CrP)as a non-specific marker of inflammation during pregnancy and lactation is unclear in impoverished populations where co-existing infections and vitamin deficiencies are ***:This cross-sectional study in Panama recruited 120 pregnant and 99 lactating Ngäbe-Buglewomen from 14 communities in rural *** history,indoor wood smoke exposure,fieldwork,BMI,vitamins A,B_(12),D,and folic acid,and inflammation markers(CrP,neutrophil/lymphocyte ratio(NLr),plateletcrit and cytokines)were *** regressions explored both associations of CrP with other inflammatory markers and associations of CrP and elevated CrP based on trimester-specific cut-offs with maternal factors,infections and vitamin ***:CrP was higher in pregnancy(51.4±4.7 nmol/L)than lactation(27.8±3.5 nmol/L)and was elevated above trimester specific cut-offs in 21%of pregnant and 30%of lactating *** deficiencies were common(vitamin A 29.6%;vitamin D 68.5%;vitamin B1268%;folic acid 25.5%)and over 50%of women had two or more concurrent deficiencies as well as multiple *** regression models highlighted differences in variables associated with CrP between pregnancy and *** pregnancy,CrP was positively associated with greater indoor wood smoke exposure,caries and hookworm and negatively associated with Ascaris and vaginal Lactobacillus and Bacteroides/Gardnerella *** with this,greater wood smoke exposure,caries as well as higher diplococcal infection score increased the odds of trimester-elevated CrP concentrations whereas longer gestational age lowered the likelihood of a trimester-elevated *** lactation,folic acid deficiency was associated with higher CrP whereas parity,number of eosinophils and Mobiluncus score were associated with lower ***,a higher BMI and Trichomonas vaginalis score increased the likelihood of an elevated CrP whereas higher parity and numbe

关键词： CrP Intestinal parasites Caries Vaginal infections Folic acid deficiency Wood smoke Neutrophil/lymphocyte ratio Plateletcrit Pregnancy Lactation

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