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1.
Arch Gerontol Geriatr ; 52(1): 106-10, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-20226544

RESUMO

Confirming the presence of heart failure (HF) in geriatric patients is made difficult by the overlapping symptoms with other diseases and by limited access to investigative techniques such as echography, and the clinical signs are either non-constant or difficult to interpret. In this context, BNP measurement could prove highly useful. We determined a cut-off value of BNP for diagnosing HF in geriatric patients and gauged its predictive power in terms of cardiovascular events, dependence and death within a 6-month timeframe. This clinical and biological study was performed in patients, 44 women and 20 men, age>65 years with suspected HF hospitalized in the geriatric unit at Emile-Roux hospital. Echography was performed at baseline examination. BNP concentrations were determined at baseline examination and at 2 and 6 months later. Renal function was assessed via the Cockroft-Gault formula. Nutritional status was assessed using the geriatric nutritional risk index (GNRI). Final reference diagnosis was established by both cardiologist and geriatrician. The diagnostic value of BNP was assessed by area under the ROC curve. The average age of the 64 patients was 84.3±7.4 years. The final diagnosis was HF in 26 patients (41%). A BNP<129pg/ml had a negative predictive value of 90% (accuracy 80%) for excluding the diagnosis of HF. BNP values were predictive of cardiovascular events over a 2-month timeframe in patients with HF and over a 6-month timeframe in the global population. BNP values were not predictive of mortality in patients with or without HF. BNP testing should help to differentiate pulmonary from cardiac etiologies of dyspnea, but a specific cut-off point has to be used in geriatric settings, mainly for patients presenting nutritional and renal dysfunctions.


Assuntos
Cardiopatias/diagnóstico , Nefropatias/complicações , Peptídeo Natriurético Encefálico/sangue , Estado Nutricional , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/fisiologia , Índice de Massa Corporal , Proteína C-Reativa/análise , Creatinina/sangue , Ecocardiografia , Feminino , Cardiopatias/sangue , Cardiopatias/complicações , Cardiopatias/fisiopatologia , Humanos , Nefropatias/sangue , Masculino , Avaliação Nutricional , Estado Nutricional/fisiologia , Prognóstico , Sensibilidade e Especificidade , Albumina Sérica/análise , Fatores Sexuais , Estatísticas não Paramétricas , Volume Sistólico/fisiologia
3.
Am J Physiol Regul Integr Comp Physiol ; 294(3): R748-55, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18056986

RESUMO

Splanchnic sequestration of amino acids (SSAA) is a process observed during aging that leads to decreased peripheral amino acid (AA) availability. The mechanisms underlying SSAA remain unknown. The aim of the present study was to determine whether a high-protein diet could increase nitrogen retention in aged rats by saturating SSAA and whether SSAA could be explained by dysregulation of hepatic nitrogen metabolism. Adult and aged male Sprague-Dawley rats were housed in individual metabolic cages and fed a normal-protein (17% protein) or high-protein diet (27%) for 2 wk. Nitrogen balance (NB) was calculated daily. On day 14, livers were isolated and perfused for 90 min to study AA and urea fluxes. NB was lower in aged rats fed a normal-protein diet than in adults, but a high-protein diet restored NB to adult levels. Isolated perfused livers from aged rats showed decreased urea production and arginine uptake, together with a release of alanine (vs. uptake in adult rats) and a hepatic accumulation of alanine. The in vivo data suggest that SSAA is a saturable process that responds to an increase in dietary protein content. The hepatic metabolism of AA in aged rats is greatly modified, and urea production decreases. This result refutes the hypothesis that SSAA is associated with an increase in AA disposal via urea production.


Assuntos
Envelhecimento/metabolismo , Aminoácidos/metabolismo , Fígado/metabolismo , Circulação Esplâncnica/fisiologia , Algoritmos , Animais , Peso Corporal/fisiologia , Corantes , Dieta , Proteínas Alimentares/metabolismo , Ingestão de Alimentos/fisiologia , Técnicas In Vitro , Verde de Indocianina , Masculino , Nitrogênio/metabolismo , Ratos , Ratos Sprague-Dawley , Ureia/metabolismo
4.
J Nutr Health Aging ; 9(6): 441-5, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16395516

RESUMO

OBJECTIVES: To assess BIA data given by Analycor 3 and some bio-impedance equations to assist geriatricians with discriminative diagnosis of hypertonic dehydration, during heat waves. DESIGN: Prospective study: a dehydrated patients group has been compared with a randomised control group. SETTING: The study was carried out in a French geriatric department, in the Emile Roux geriatric hospital. PARTICIPANTS: 36: six men and twelve women in each group. MEASUREMENTS: The most valuable clinical indicators of dehydration severity were recorded and scored. BIA measurements were performed with an Analycor 3 analyzer; TBW was calculated from impedances at 50 and 100 kHz, ECW from impedance at 5 kHz; Calculations were made also with formula described in the literature, validated in healthy or in institutionalised elderly subjects. RESULTS: TBW and ECW values were always lower in dehydrated group than in control group, but without significance, whatever the applied formula; however ICW values calculated with "manufacturers equations" significantly decreased in dehydrated group. Data given by the analyzer used in this study, as well as BIA age specific equations discriminated the severely hypertonic dehydrated patients sub-group, but not the mildly hypertonic dehydrated patients sub-group. CONCLUSION: The BIA data given by the analyzer used in this study assist geriatricians at bedside with discriminative diagnosis of hypertonic dehydration, especially in severe hypertonic dehydration, but data given by the analyzer used in this study, as well as age specific equations are sometimes in poor agreement with clinical and biological parameters usually selected to assess dehydration, in mildly dehydrated patients.


Assuntos
Desidratação/diagnóstico , Impedância Elétrica , Avaliação Geriátrica/métodos , Temperatura Alta , Idoso , Idoso de 80 Anos ou mais , Água Corporal/metabolismo , Diagnóstico Diferencial , Feminino , França , Humanos , Masculino , Estudos Prospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença
7.
Biochim Biophys Acta ; 1539(3): 256-64, 2001 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-11420123

RESUMO

Incubation of Jurkat cells in the presence of H2O2 either directly added to the culture medium or generated with glucose oxidase, menadione or the couple xanthine/xanthine oxidase induced a marked decrease of phosphatidylserine synthesis in the absence of changes in the synthesis of phosphatidylcholine and phosphatidylethanolamine. Concentration dependent response curves indicated that H2O2 induced inhibition of phosphatidylserine synthesis with an IC(50)=5 microM while both induction of tyrosine phosphorylation of proteins and Ca(2+) signals were obtained with an EC(50)=300 microM. The tyrosine kinase and Ca(2+) independent mechanism was confirmed by comparing the H2O2-induced and the CD3-induced inhibition of phosphatidylserine synthesis using several Jurkat clones differing in the expression of cell surface receptors such as CD3/TCR and CD45 and protein tyrosine kinase such as p72syk, ZAP-70 and p56lck. While CD3-induced inhibition of phosphatidylserine synthesis necessitates protein tyrosine phosphorylation and Ca(2+) signals, H2O2 provoked its effect in all the clones studied independently of the presence or absence of the proteins previously shown to be key elements in T cell signal transduction. Conversely, the antioxidant molecule, butylated hydroxanisole, generates an increased PtdSer synthesis, suggesting that the synthesis of this phospholipid is regulated by the redox status of the cells.


Assuntos
Peróxido de Hidrogênio/farmacologia , Fosfatidilserinas/biossíntese , Linfócitos T/efeitos dos fármacos , Antioxidantes/farmacologia , Transporte Biológico , Hidroxianisol Butilado/farmacologia , Cálcio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Interações Medicamentosas , Humanos , Células Jurkat , Proteínas Tirosina Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Linfócitos T/metabolismo
8.
J Immunol ; 166(1): 396-402, 2001 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-11123317

RESUMO

CD5 is a transmembrane coreceptor that modulates activation and differentiation signals mediated by the Ag-specific receptor present on both T and B1a lymphocytes. CD5 lacks intrinsic catalytic activity, and its immunomodulatory properties result from intracellular interactions mediated by the CD5 cytoplasmic tail. The nature of these interactions is currently a matter of investigation. Here, we present a selective mutagenesis analysis of two conserved threonine residues (T410 and T412) located at the membrane-proximal cytoplasmic region of CD5. These residues are contained within consensus phosphorylation motifs for protein kinase C and are shown here to be critical for in vivo protein kinase C-mediated phosphorylation of CD5. Functional studies revealed that the integrity of T410 and T412 is also critical for CD5-mediated phosphatidylcholine-specific phospholipase C (PC-PLC) activation and phorbol ester-mediated inhibition of Ab-induced internalization of CD5. These results strongly argue in favor of a role for T410 and T412 in the signaling mediated by CD5.


Assuntos
Antígenos CD5/fisiologia , Sequência Conservada , Transdução de Sinais/imunologia , Treonina/fisiologia , Substituição de Aminoácidos/genética , Substituição de Aminoácidos/imunologia , Animais , Anticorpos Monoclonais/farmacologia , Antígenos CD5/genética , Antígenos CD5/imunologia , Antígenos CD5/metabolismo , Membrana Celular/imunologia , Membrana Celular/metabolismo , Citoplasma/genética , Citoplasma/imunologia , Diglicerídeos/metabolismo , Humanos , Células Jurkat , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/metabolismo , Fosforilação/efeitos dos fármacos , Proteína Quinase C/fisiologia , Ratos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Acetato de Tetradecanoilforbol/farmacologia , Treonina/genética , Treonina/metabolismo , Transfecção
9.
Eur Cytokine Netw ; 11(2): 293-9, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10903809

RESUMO

Most of the data accumulated to date on the immunoregulatory effects of prostaglandins (PG) on T cell activation stem from the archetypal inhibitory effect of PGE(2). In this study we provide instead, the first evidence that exogenous PGB(2), a catabolic metabolite of PGE(2), synergizes with signals delivered by T cell receptor (TCR) engagement to induce interleukin-2 (IL-2) production and IL-2 receptor (IL-2R) alpha-expression in Jurkat cells. Accordingly, PGB(2) enhances the proliferation of anti-CD3-activated peripheral blood lymphocytes (PBL). In terms of cellular signaling, we present evidence that PGB(2) activates tyrosine kinase activities and efficiently increases c-fos mRNA expression and nuclear factor-kappa B (NF-kappa B) translocation to the nucleus. Owing to these features, PGB(2) appears as a new lipid mediator capable of delivering an ancillary signal leading to T lymphocyte activation.


Assuntos
Ativação Linfocitária/efeitos dos fármacos , Prostaglandinas B/farmacologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Divisão Celular/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Genes fos/efeitos dos fármacos , Humanos , Técnicas In Vitro , Interleucina-2/biossíntese , Interleucina-2/genética , Células Jurkat , Lectinas Tipo C , NF-kappa B/metabolismo , Proteínas Tirosina Quinases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Antígenos de Linfócitos T/efeitos dos fármacos , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Interleucina-2/genética , Receptores de Interleucina-2/metabolismo , Transdução de Sinais , Linfócitos T/citologia
10.
Clin Chem ; 46(6 Pt 1): 848-53, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10839775

RESUMO

BACKGROUND: Measurement of keto-acids is important in various clinical situations. The aim of the present work was to develop a rapid HPLC method for the determination of keto-acids in human serum and to assess the concentrations of these acids in young adults and institutionalized elderly adults. This method was applied to the determination of blood keto-acid concentrations of young adults and institutionalized elderly people, divided into age groups METHODS: Four keto-acids (alpha-ketoisocaproate, alpha-ketoisovalerate, alpha-keto-beta-methylvalerate, and pyruvate) were derivatized with o-phenylenediamine to give fluorescent derivatives. After the sample preparation step (75 min to prepare 20 samples), the derivatives were separated chromatographically on a reversed-phase column using a binary gradient. RESULTS: The fluorometric detection of the four keto-acids was rapid, <12 min. The method is repeatable and reproducible: the CVs were <6% and <11%, respectively, for each of the keto-acids. We found no significant difference between males and females. Concentrations of the branched-chain keto-acids decreased after age 60 years, especially alpha-ketoisocaproate, which decreased approximately 40%. CONCLUSIONS: The proposed method allows rapid and reliable measurement of keto-acids. The data demonstrate that changes in branched-chain keto-acids concentrations in serum occur with age.


Assuntos
Cetoácidos/sangue , Ácido Pirúvico/sangue , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Cromatografia Líquida de Alta Pressão , Feminino , Fluorometria , Hospitais , Humanos , Cetoácidos/química , Masculino , Pessoa de Meia-Idade , Quinoxalinas/química
11.
J Cell Physiol ; 183(1): 65-73, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10699967

RESUMO

We studied the long-terms effects of interleukin-1beta (IL-1beta; 3 to 6 h) on alpha-(methylamino) isobutyric acid (MeAIB), a nonmetabolizable amino acid transported by system A. We found that IL-1beta induced a large decrease in MeAIB uptake by human osteoarthritic synovial cells and a concomitant increase in prostaglandin E(2) (PGE(2)) synthesis. Therefore, we investigated whether PGE(2) acts as a mediator for the long-term action of IL-1beta. We found that exogenous PGE(2) inhibited MeAIB uptake, and that AH6809, a PGE(2) receptor antagonist, inhibited IL-1beta-mediated MeAIB uptake. To identify the enzymes involved in the IL-1beta-mediated synthesis of PGE(2) that inhibits MeAIB uptake, we studied the expression of secreted (s) and cytosolic (c) phospholipase A(2) (PLA(2)). Because both were expressed, we selected a broad spectrum of inhibitors to determine which of the two PLA(2)s was involved. We used AACOCF3, a cPLA(2) inhibitor, and dithiothreitol (DTT) and bromophenacyl bromide (BPB), which are sPLA(2) inhibitors. Our results suggest that the PLA(2) involved in the IL-1beta-mediated synthesis of PGE(2) was sPLA(2). We also showed the expression of cyclooxygenase (COX)-2 and its partial involvement using a potent selective COX-2 inhibitor, L-745337. These findings provide insight into the mechanisms underlying the IL-1beta-mediated regulation of transport system A. The Il-1beta-induced inhibition of MeAIB uptake in human osteoarthritic synovial cells thus seems to be essentially mediated by PGE(2) production via the activation of sPLA(2) and the partial activation of COX-2.


Assuntos
Proteínas de Transporte/metabolismo , Dinoprostona/fisiologia , Interleucina-1/farmacologia , Osteoartrite/fisiopatologia , Sistemas do Segundo Mensageiro/fisiologia , Membrana Sinovial/fisiopatologia , Xantonas , beta-Alanina/análogos & derivados , Sistemas de Transporte de Aminoácidos , Ácidos Araquidônicos/farmacologia , Transporte Biológico/efeitos dos fármacos , Proteínas de Transporte/efeitos dos fármacos , Células Cultivadas , Ciclo-Oxigenase 2 , Citosol/enzimologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Indanos/farmacologia , Isoenzimas/genética , Isoenzimas/metabolismo , Cinética , Proteínas de Membrana , Osteoartrite/patologia , Fosfolipases A/genética , Fosfolipases A/metabolismo , Prostaglandina-Endoperóxido Sintases/genética , Sistemas do Segundo Mensageiro/efeitos dos fármacos , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/patologia , Xantenos/farmacologia , beta-Alanina/farmacocinética
12.
Biochem Pharmacol ; 59(7): 855-63, 2000 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-10718344

RESUMO

Early in the apoptotic process, CD95 induces a translocation of phosphatidylserine (PtdSer) from the inner to the outer leaflet of the cellular plasma membrane. In mammalian cells, PtdSer is only synthesized through a calcium-dependent exchange of the polar head group of pre-existing phospholipids, either phosphatidylcholine or phosphatidylethanolamine, by a serine. Using a pharmacological approach, we examined the influence of PtdSer synthesis on CD95-induced PtdSer exposure at the surface of Jurkat cells. We found that CD3/TCR triggering or thapsigargin treatment of Jurkat cells was accompanied both by a decreased PtdSer synthesis and by a strong reduction of CD95-induced PtdSer at the cell surface, as monitored by fluorescence-activated cell sorting (FACS) analysis of annexin V-fluorescein isothiocyanate (FITC)-labeled cells. PtdSer synthesis through the serine-base exchange enzyme system thus appeared as one of the mechanisms implicated in the recently discovered CD3/TCR-induced down-regulation of CD95-induced apoptosis. Conversely, increasing the activity of the serine-base exchange enzyme system with different drugs, either the K+ channel blocker quinine, the cationic amphiphil stearylamine, or three different calmodulin antagonists, chlorpromazine, trifluoperazine, and N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W7), resulted in an increased appearance of PtdSer at the surface of CD95-treated cells. Both PtdSer synthesis and CD95-induced annexin V-FITC reactivity were abrogated in ATP-depleted cells. Also, modifying the membrane potential with valinomycin (hyperpolarization) or either gramicidin or KCl (depolarization) demonstrated a strong relationship between PtdSer synthesis and annexin V-FITC reactivity in CD95-treated cells. Together, our results indicate that CD95-induced exposure of PtdSer at the cell surface could be regulated by the activity of the serine-base exchange enzyme system.


Assuntos
Apoptose , Transferases de Grupos Nitrogenados/metabolismo , Fosfatidilserinas/fisiologia , Receptor fas/metabolismo , Trifosfato de Adenosina/metabolismo , Humanos , Células Jurkat , Cinética , Ativação Linfocitária , Potenciais da Membrana , Fosfatidilserinas/biossíntese , Serina , Linfócitos T/efeitos dos fármacos , Linfócitos T/fisiologia
13.
Eur J Biochem ; 267(4): 984-92, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10672006

RESUMO

Sodium ortho-vanadate (Na3VO4), an inhibitor of protein tyrosine phosphatase, induces a rapid (15 min) and strong inhibition of phosphatidylserine synthesis with an IC50 = 100 microM. The mode of action of Na3VO4 was compared to that of CD3 mAbs. It was found that Na3VO4 bypasses the major CD3-induced T cell activation signals including protein tyrosine phosphorylation, p56lck activation and the generation of second messengers including inositol phosphates and its subsequent Ca2+ mobilization as well as diacylglycerol production. These facts were confirmed by using a panel of Jurkat clones that differs by the expression of either tyrosine kinases involved in the CD3-induced T cell activation pathway such as p56lck, p72syk and ZAP-70 or some cell surface receptors such as the CD3/TCR complex or the CD45 phosphatase.


Assuntos
Complexo CD3/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Ativação Linfocitária/efeitos dos fármacos , Fosfatidilserinas/biossíntese , Linfócitos T/imunologia , Vanadatos/farmacologia , Anticorpos Monoclonais , Cálcio/metabolismo , ATPases Transportadoras de Cálcio/antagonistas & inibidores , ATPases Transportadoras de Cálcio/metabolismo , Citosol/efeitos dos fármacos , Citosol/metabolismo , Diglicerídeos/análise , Retículo Endoplasmático/enzimologia , Retículo Endoplasmático/metabolismo , Humanos , Inositol 1,4,5-Trifosfato/análise , Células Jurkat , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/metabolismo , Monoéster Fosfórico Hidrolases/antagonistas & inibidores , Monoéster Fosfórico Hidrolases/metabolismo , Fosforilação/efeitos dos fármacos , Fosfotirosina/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Sistemas do Segundo Mensageiro , Especificidade por Substrato , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo
14.
Biochem Biophys Res Commun ; 266(2): 497-503, 1999 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-10600531

RESUMO

Phosphatidylserine synthesis as measured by the incorporation of [(3)H]serine into phosphatidylserine (PtdSer) through the serine-base exchange enzyme system (serine-BEES) is markedly inhibited in Jurkat cells treated with caffeine. The caffeine-induced inhibition was compared to that observed in cells treated with either CD3 mAb or thapsigargin. While CD3- and thapsigargin-induced inhibition was related to the release of Ca(2+) from the endoplasmic reticulum (ER), a process that deprives the serine-BEES of its major cofactor, caffeine modified PtdSer synthesis in the absence of decreased Ca(2+) content of ER. Using Jurkat clones differing by the expression of cell surface markers or protein tyrosine kinases implicated in the CD3/TCR signal transmission pathway, we have shown that CD3 mAb-induced inhibition of PtdSer synthesis necessitates the expression of both the CD3/TCR and the protein tyrosine phosphatase CD45 at the cell surface as well as the presence of p56(lck) and ZAP-70 protein tyrosine kinases. By contrast, thapsigargin, a blocker of the Ca(2+)-ATPase of the ER, known for its Ca(2+) releasing properties, inhibited PtdSer synthesis in all the Jurkat clones tested, indicating that this compound bypasses the CD3/TCR-induced signals. Despite its lack of effect on Ca(2+) release from ER and on protein tyrosine phosphorylations, caffeine inhibited PtdSer synthesis in all the Jurkat clones. The use of several cAMP-inducing drugs and of others xanthine derivatives indicated that caffeine modify PtdSer synthesis either by a direct action on the serine-BEES or by a modification of the structure of the phospholipids used as substrate by the enzyme.


Assuntos
Complexo CD3/imunologia , Cafeína/farmacologia , Sinalização do Cálcio , Fosfatidilserinas/biossíntese , Proteínas Tirosina Quinases/metabolismo , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Cálcio/metabolismo , ATPases Transportadoras de Cálcio/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Humanos , Ionomicina/farmacologia , Células Jurkat , Fosforilação/efeitos dos fármacos , Transdução de Sinais , Tapsigargina/farmacologia
15.
Cell Biol Int ; 23(1): 7-12, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10527543

RESUMO

The effects of glucagon on amino acid transport in rat hepatocytes are not fully understood. We examined the effect of this hormone on alanine, serine and cysteine preferring system (system ASC)-mediated amino acid transport in rat hepatocyte monolayers using 2-aminoisobutyric acid (AIB) and l -cysteine. Glucagon induced a time and protein synthesis-dependent stimulation of Na(+)-dependent alanine preferring system (system A)-independent AIB transport. The glucagon-induced increase in transport activity was not modified by substrate starvation and not related to changes in the intracellular pool of amino acids. Glucagon did not modify system ASC activity measured by l -cysteine. Therefore the transport activity of AIB independent of system A stimulated by glucagon cannot be attributed to system ASC. This suggests a Na(+)-dependent transport system in rat hepatocytes not identified until now.


Assuntos
Aminoácidos/metabolismo , Glucagon/farmacologia , Fígado/metabolismo , Inibidores da Síntese de Proteínas/farmacologia , Animais , Transporte Biológico/efeitos dos fármacos , Células Cultivadas , Masculino , Ratos , Ratos Sprague-Dawley , Sódio/metabolismo
16.
Clin Nutr ; 18(1): 5-13, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10459077

RESUMO

Plasma branched-chain amino acid (BCAA) levels are decreased in patients with liver cirrhosis, owing to an increase in BCAA tissue uptake and/or catabolism and a decrease in BCAA production from proteins. Non-specific factors such as malnutrition worsen this picture. Studies of BCAA fluxes and protein turnover in cirrhotic patients have given conflicting results due to patient heterogeneity, differences in method and bias in the expression of results. In well compensated cirrhosis, muscle wasting is moderate and probably due more to decreased protein synthesis than to increased protein catabolism. Hyperinsulinemia has been suggested as the main cause of decreased BCAA levels, by increasing BCAA uptake in muscle and additionally in adipose tissue. However, as depletion of fat stores is frequent in cirrhosis, this effect is certainly quantitatively weak. Also, there is no correlation between state of hyperinsulinemia and decrease in BCAA levels. An effect of cytokines (IL1 and TNF) on muscle BCAA catabolism is a possibility. Until recently, the contribution of the liver to abnormal BCAA metabolism has been underestimated. In cirrhotic liver an increase in liver transamination of branched-chain keto acids (BCKAs) has been suggested and may result from inhibition of liver BCKA dehydrogenase. A modification of protein turnover in cirrhotic liver must be also considered. Lastly, the contribution of non-hepatocyte liver cells, which are activated in cirrhosis, remains to be assessed.


Assuntos
Aminoácidos de Cadeia Ramificada/metabolismo , Cirrose Hepática/metabolismo , Aminoácidos de Cadeia Ramificada/sangue , Humanos , Interleucina-1/fisiologia , Leucina/metabolismo , Músculos/metabolismo , Estado Nutricional , Proteínas/metabolismo , Fator de Necrose Tumoral alfa/fisiologia
17.
Eur J Gastroenterol Hepatol ; 11(7): 755-9, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10445796

RESUMO

OBJECTIVES: Patients with liver cirrhosis are at high risk of severe septic complications such as spontaneous bacterial peritonitis (SBP) and bacteraemia. The aims of this study were to assess intestinal permeability in patients with liver cirrhosis and to search for a relationship between an impaired intestinal permeability and the occurrence of severe septic complications. METHODS: Intestinal permeability was assessed in a group of 80 cirrhotic patients (Child A, n = 13; Child B, n = 26; Child C, n = 41) and 28 healthy control subjects. A severe septic complication (bacteraemia and/or SBP) occurred in 16 patients, within 10 days before (n = 8 cases) or after (n = 8 cases) the test was performed. Lactulose (LAC) 10 g was given orally together with mannitol (MAN) 5 g, and urinary excretion rates were determined. RESULTS: Urinary mannitol excretion (MAN%) was lower while the LAC/MAN ratio was higher in patients than in control subjects (P < 0.001); these abnormalities were more marked in Child C patients (Child C patients vs control subjects: MAN%, 8.20 +/- 0.79 vs 14.59 +/- 0.58, P < 0.001; LAC/MAN, 0.066 +/- 0.026 vs 0.017 +/- 0.001, P < 0.02). When compared with non-infected patients, septic patients had a lower MAN% and an increased LAC/ MAN ratio (5.45 +/- 1.12 vs 9.83 +/- 0.87, P < 0.02; 0.130 +/- 0.063 vs 0.029 +/- 0.005, P < 0.02). CONCLUSION: Although the main mechanism involved in the decrease in MAN% is likely a reduction in area of the intestinal absorptive surface, these results argue in favour of an increased intestinal permeability in liver cirrhosis, especially in patients with severe infectious complications. The impairment of intestinal function barrier may contribute to severe septic complications in these patients.


Assuntos
Bacteriemia/fisiopatologia , Intestinos/fisiopatologia , Cirrose Hepática/fisiopatologia , Peritonite/fisiopatologia , Bacteriemia/complicações , Translocação Bacteriana , Permeabilidade da Membrana Celular , Feminino , Humanos , Absorção Intestinal , Lactulose/urina , Cirrose Hepática/complicações , Cirrose Hepática/urina , Masculino , Manitol/urina , Pessoa de Meia-Idade , Peritonite/complicações
18.
Metabolism ; 48(2): 190-3, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10024080

RESUMO

We investigated the role of the nitric oxide (NO) synthase (NOS) pathway in muscular metabolism during endotoxemia in four groups of male Wistar rats. Two groups were injected with the lipopolysaccharide (LPS) of Escherichia coli (3 mg/kg), with one group treated using N(G)-nitro-L-arginine methylester ([L-NAME] 85 mg/kg/d) and the other not. The two control groups included one treated with L-NAME and the other not. After 24 hours of fasting, the rats were fed by controlled enteral nutrition and killed on day 3. The results showed that (1) NOS inhibition was detrimental during endotoxemia, increasing lethality from 20% to 80.5%, and (2) NOS inhibition did not modify the hypercatabolic state consecutive to endotoxemia, particularly at the muscular level (nitrogen balance, total-body and muscular weight loss, and muscular protein and glutamine concentrations). However, myofibrillar catabolism was delayed in the LPS-NAME group. In conclusion, NO production is of major importance for survival after an endotoxemic challenge, but contributes weakly to the metabolic response of muscle to injury.


Assuntos
Arginina/metabolismo , Endotoxemia/metabolismo , Músculo Esquelético/metabolismo , Óxido Nítrico/metabolismo , Animais , Peso Corporal/fisiologia , Inibidores Enzimáticos/farmacologia , Ácido Glutâmico/metabolismo , Masculino , Proteínas Musculares/metabolismo , Miofibrilas/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Nitrogênio/urina , Ratos , Ratos Wistar
19.
Scand J Gastroenterol ; 34(1): 29-34, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10048729

RESUMO

BACKGROUND: Impaired intestinal function could account for diarrhoea and weight loss, which are common features of advanced human immunodeficiency virus (HIV) infection. METHODS: We assessed intestinal permeability to lactulose and mannitol and absorption of D-xylose in 96 HIV-infected patients (group I: asymptomatic subjects (CDC-A); group II: symptomatic subjects (CDC-B or C) without body weight loss and/or diarrhoea; group III: 25 acquired immunodeficiency syndrome (AIDS) patients (CDC-C) with severe body weight loss and/or diarrhoea) and 10 healthy subjects as controls. RESULTS: An incremental decrease in urinary D-xylose recoveries was observed, with all groups statistically different from each other. Impaired intestinal permeability was only found in patients of group III (statistically different from all other groups). CONCLUSIONS: These findings suggest a loss of intestinal functional absorptive surface as HIV disease progresses. This process may be present at the early stage of infection. Impaired intestinal permeability is observed later in AIDS patients when digestive signs are present, particularly diarrhoea.


Assuntos
Infecções por HIV/fisiopatologia , Absorção Intestinal/fisiologia , Adulto , Idoso , Índice de Massa Corporal , Contagem de Linfócito CD4 , Creatinina/sangue , Diarreia/complicações , Diarreia/metabolismo , Feminino , Infecções por HIV/complicações , Infecções por HIV/imunologia , Humanos , Absorção Intestinal/imunologia , Mucosa Intestinal/metabolismo , Lactulose/metabolismo , Lactulose/urina , Masculino , Manitol/metabolismo , Manitol/urina , Pessoa de Meia-Idade , Estado Nutricional/fisiologia , Albumina Sérica/metabolismo , Redução de Peso , Xilose/metabolismo , Xilose/urina
20.
J Immunol ; 161(11): 6022-9, 1998 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-9834084

RESUMO

CD5 is a lymphocyte surface glycoprotein with a long cytoplasmic domain suitable for phosphorylation and signal transduction, which is involved in the modulation of Ag-specific receptor-mediated activation and differentiation signals. In this study, we use Jurkat T cell transfectants of CD5 cytoplasmic tail mutants to reveal phosphorylation sites relevant to signal transduction. Our results show that casein kinase II (CKII) is responsible for the constitutive phosphorylation of CD5 molecules at a cluster of three serine residues located at the extreme C terminus (S458, S459, and S461). Furthermore, the yeast two-hybrid system demonstrates the specific association between the C-terminal regions of the CD5 cytoplasmic tail and the regulatory beta subunit of CKII. We demonstrate that CKII associates with and phosphorylates the C-terminal region of CD5, a conserved domain known to be relevant for the generation of second lipid messengers, and thereby enables at least one component of its signaling function.


Assuntos
Antígenos CD5/fisiologia , Fragmentos de Peptídeos/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Serina/metabolismo , Transdução de Sinais/imunologia , Sequência de Aminoácidos , Sítios de Ligação/imunologia , Antígenos CD5/genética , Antígenos CD5/metabolismo , Caseína Quinase II , Diglicerídeos/metabolismo , Humanos , Células Jurkat , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Fosforilação , Transdução de Sinais/genética , Especificidade por Substrato/imunologia
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