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1.
Meat Sci ; 142: 38-43, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29656274

RESUMO

Cortisol and corticosterone in saliva were evaluated as pig stress biomarkers, using pig genotype (Duroc, L62 or Pietrain) and lairage time in the slaughterhouse (0, 2.0, 4.0 or 6.0 h) as controlled variables. Although some pigs were found to be carriers of stress susceptibility, all were healthy heterozygous individuals. Pre-slaughter transport increased cortisol levels in saliva above 3.0 µg/L (medium stress), and 4.0 h of lairage in the slaughterhouse raised them above 6.0 µg/L, whereas corticosterone concentrations exceeded 4 µg/L, which are suggestive of high stress. The highest cortisol levels were detected in the Duroc genotype. Other factors such as food deprivation, background noise, the presence of a large number of animals waiting to be slaughtered, mixing with unfamiliar animals or recent mixing of genders may also influence stress. Corticosterone proved a reliable indicator of high stress only. Meat quality from the pig breeds studied was not affected by lairage in the slaughterhouse for up to 6.0 h.


Assuntos
Matadouros , Carne Vermelha/análise , Estresse Fisiológico , Sus scrofa/fisiologia , Animais , Biomarcadores , Corticosterona/metabolismo , Feminino , Hidrocortisona/metabolismo , Masculino , Saliva/química , Meios de Transporte
2.
Crit Rev Food Sci Nutr ; 55(11): 1590-617, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24279584

RESUMO

Dioxins include polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and part of polychlorinated biphenyls (PCBs). Only the compounds that are chlorinated at the 2,3,7, and 8 positions have characteristic dioxin toxicity. PCDDs, PCDFs and PCBs accumulate in the food chain due to their high lipophilicity, high stability, and low vapor pressure. They are not metabolized easily; however their hydroxylated metabolites are detected in feces. They cause a wide range of endocrine disrupting effects in experimental animals, wildlife, and humans. Endocrine related effects of PCDDs, PCDFs and PCBs on thyroid hormones, neurodevelopment and reproductive development were referenced. In addition, some studies of contamination of foods, bioaccumulation, dietary exposure assessment, as well as challenges of scientific research in these compounds were reviewed.


Assuntos
Benzofuranos/intoxicação , Alimentos/efeitos adversos , Bifenilos Policlorados/intoxicação , Dibenzodioxinas Policloradas/análogos & derivados , Animais , Benzofuranos/análise , Benzofuranos/metabolismo , Dibenzofuranos Policlorados , Poluentes Ambientais/intoxicação , Humanos , Bifenilos Policlorados/análise , Bifenilos Policlorados/metabolismo , Dibenzodioxinas Policloradas/análise , Dibenzodioxinas Policloradas/metabolismo , Dibenzodioxinas Policloradas/intoxicação
3.
Sci Total Environ ; 468-469: 1007-13, 2014 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-24095964

RESUMO

Fish oil has been identified as one of the most important contributors to the levels of polychlorinated biphenyls (PCBs) in food and feed products. In this study, PCB adsorption from fish oil onto activated carbon (AC), other sustainable adsorbents (mussel shell and wood waste ashes) and organic solvent such as ethanol were compared and optimized. Regarding to adsorbents, PCBs were extracted from fish oil by a 2.0% adsorbent material dose, during 6.0 h at 25 °C. Solvent extraction was carried out using 2 × 5.0 mL ethanol by manually stirring for 3.0 min, and then by Ultrasound-Assisted Solvent Extraction (UASE) for 5.0 min. The results showed that removal rates obtained by using adsorbent materials ranged from 0.0 to 10% for marker PCBs, from 0.0 to 37% for mono-ortho-PCBs, from 0.0 to 74% for PCB11 and from 0.0 to 95% for non-ortho-PCBs. Regarding to solvent extraction, ethanol was used by manually stirring and then by Ultrasound-Assisted Solvent Extraction (UASE). The samples were then centrifuged (2000 rpm/10 min) and the alcoholic phase was removed. With this method, removal efficiencies were much better (85-116%); nevertheless, high eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) removal rates (70-78 and 71-79%, respectively) were detected. We can conclude that adsorption with adsorbents depends on the geometry of PCB congeners, as well as both type of adsorption material and their origin, and that several sorption cycles are needed. Adsorption with ethanol could be the most effective methodology but nutritional quality was impaired, what makes necessary to look for other not so polar removal solvents.


Assuntos
Descontaminação/métodos , Óleos de Peixe/química , Bifenilos Policlorados/análise , Adsorção , Exoesqueleto/química , Animais , Bivalves/química , Carvão Vegetal/química , Ácidos Docosa-Hexaenoicos/química , Ácido Eicosapentaenoico/química , Etanol , Pinus/química , Bifenilos Policlorados/química , Espanha
4.
Antimicrob Agents Chemother ; 57(6): 2541-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23507287

RESUMO

Agaricus brasiliensis (syn. A. subrufescens), a basidiomycete fungus native to the Atlantic forest in Brazil, contains cell walls rich in glucomannan polysaccharides. The ß-(1 → 2)-gluco-ß-(1 → 3)-mannan was isolated from A. brasiliensis mycelium, chemically modified by sulfation, and named MI-S. MI-S has multiple mechanisms of action, including inhibition of herpes simplex virus (HSV) attachment, entry, and cell-to-cell spread (F. T. G. S. Cardozo, C. M. Camelini, A. Mascarello, M. J. Rossi, R. J. Nunes, C. R. Barardi, M. M. de Mendonça, and C. M. O. Simões, Antiviral Res. 92:108-114, 2011). The antiherpetic efficacy of MI-S was assessed in murine ocular, cutaneous, and genital infection models of HSV. Groups of 10 mice were infected with HSV-1 (strain KOS) or HSV-2 (strain 333). MI-S was given either topically or by oral gavage under various pre- and posttreatment regimens, and the severity of disease and viral titers in ocular and vaginal samples were determined. No toxicity was observed in the uninfected groups treated with MI-S. The topical and oral treatments with MI-S were not effective in reducing ocular disease. Topical application of MI-S on skin lesions was also not effective, but cutaneously infected mice treated orally with MI-S had significantly reduced disease scores (P < 0.05) after day 9, suggesting that healing was accelerated. Vaginal administration of MI-S 20 min before viral challenge reduced the mean disease scores on days 5 to 9 (P < 0.05), viral titers on day 1 (P < 0.05), and mortality (P < 0.0001) in comparison to the control groups (untreated and vehicle treated). These results show that MI-S may be useful as an oral agent to reduce the severity of HSV cutaneous and mucosal lesions and, more importantly, as a microbicide to block sexual transmission of HSV-2 genital infections.


Assuntos
Agaricus/química , Antivirais/uso terapêutico , Polissacarídeos Fúngicos/farmacologia , Herpes Simples/tratamento farmacológico , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Animais , Antivirais/farmacologia , Chlorocebus aethiops , Feminino , Polissacarídeos Fúngicos/química , Herpes Genital/tratamento farmacológico , Herpes Genital/virologia , Herpes Simples/virologia , Humanos , Ceratite Herpética/tratamento farmacológico , Ceratite Herpética/virologia , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana/métodos , Sulfatos , Resultado do Tratamento , Células Vero
5.
An Pediatr (Barc) ; 75(1): 13-20, 2011 Jul.
Artigo em Espanhol | MEDLINE | ID: mdl-21420916

RESUMO

BACKGROUND: The 2009 H1N1 influenza A virus infection pandemic was an important challenge for public health systems worldwide. MATERIAL AND METHODS: A prospective study including all patients with an influenza-like illness, with microbiological criteria for 2009 H1N1 virus, from July to December 2009 seen in the paediatric emergency department. Viral testing was performed using multiplex real-time reverse transcription polymerase chain reaction (RT-PCR). We analysed the number of visits to, and hospital admissions from, our emergency department. We compared patients with laboratory-confirmed 2009 H1N1 virus with non-confirmed ones. RESULTS: A total of 1144 patients with microbiological criteria were identified. Of these, 513 (44.8%) were admitted to hospital, 12 of them (1%) to the PICU and 3 (0.3%) died. The majority of the patients (824; 72%) had some underlying medical condition. Of the 1144 patients, 412 (36%) had RT-PCR confirmed 2009 H1N1 infection, and 732 (64%) were not confirmed. The mean age of patients with 2009 H1N1 infection was higher than those not infected (median age: 7.4 vs 4.1 years; p<.001). Laboratory-confirmed 2009 pandemic H1N1 influenza patients had more underlying high-risk conditions (OR: 2.21 [1.65-2.96]), suffered from pneumonia in less cases (OR: 0.33 [0.23-0.49]) and were admitted to hospital in less cases (OR: 0.19 [0.14-0.24]). In our emergency department, we identified an important increase in the number of visits (12%) and admissions (5.7%) compared to the previous year, 2008. CONCLUSIONS: The 2009 pandemic H1N1 influenza caused significant morbidity but the mortality was not significant. The majority of children with laboratory-confirmed 2009 H1N1 virus had uncomplicated illnesses despite the increased presence of high-risk conditions.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana/epidemiologia , Pandemias , Criança , Pré-Escolar , Serviço Hospitalar de Emergência , Feminino , Hospitais , Humanos , Masculino , Estudos Prospectivos
7.
J Hazard Mater ; 178(1-3): 273-81, 2010 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-20117882

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) can be formed during the refinery processes of crude petroleum. Their removal is of great importance. The same happens with other organic solvents used for the extraction of PAHs (hexane, acetonitrile...), which can be polluted with PAHs. Kinetic and equilibrium batch sorption tests were used to investigate the effect of wood ashes wastes as compared to activated carbon on the sorption of three representative PAHs from n-hexane and acetonitrile. Mussel shell ashes were discarded for batch sorption experiments because they were the only ashes containing PAHs. The equilibrium time was reached at 16 h. Physical sorption caused by the aromatic nature of the compounds was the main mechanism that governed the PAHs removal process. Our investigation revealed that wood ashes obtained at lower temperature (300 degrees C) did not show any PAHs sorption, while ashes obtained at higher temperature (>500 degrees C) have adsorbent sites readily available for the PAH molecules. An increase in the molecular weight of PAHs has a strong effect on sorption wood ashes wastes. As low the wood ashes particle size as high the sorption of PAHs, as a result of differences in adsorbent sites. The performance of wood ash wastes vs. activated carbon to remove 10 PAHs from organic solvents is competitive in price, and a good way for waste disposal.


Assuntos
Resíduos Industriais/análise , Hidrocarbonetos Policíclicos Aromáticos/isolamento & purificação , Solventes/química , Acetonitrilas/química , Adsorção , Animais , Bivalves/química , Hexanos/química , Cinética , Peso Molecular , Tamanho da Partícula , Hidrocarbonetos Policíclicos Aromáticos/química , Temperatura , Termodinâmica , Madeira
8.
J Hazard Mater ; 164(2-3): 769-75, 2009 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-18829159

RESUMO

The agronomic utility of a solid waste, waste bentonite (WB), from wine companies was assessed. In this sense, the natural characteristics of the waste were measured, followed by the monitoring of its effects on the adsorption/desorption behaviour of three quaternary herbicides in acid soils after the addition of increasing levels of waste. This was done with the intention of studying the effect of the added organic matter on their adsorption. The high content in C (294 g kg(-1)), N (28 g kg(-1)), P (584 mg kg(-1)) and K (108 g kg(-1)) of WB turned it into an appropriate amendment to increase soil fertility, solving at the same time its disposal. WB also reduced the potential Cu phytotoxicity due to a change in Cu distribution towards less soluble fractions. The adsorption of the herbicides paraquat, diquat and difenzoquat by acid soils amended with different ratios of WB was measured. In all cases, Langmuir equation was fitted to the data. Paraquat (PQ) and diquat (DQ) were adsorbed and retained more strongly than difenzoquat (DFQ) in the acid soil studied. However, the lowest retention of DFQ in an acid soil can be increased by amendment with organic matter through a solid waste from wineries, and it is enough for duplicate retention a dosage rate of 10t/ha. Anyway, detritivores ecology can still be affected. Detritivores are the organisms that consume organic material, and in doing so contribute to decomposition and the recycling of nutrients. The term can also be applied to certain bottom-feeders in wet environments, which play a crucial role in benthic ecosystems, forming essential food chains and participating in the nitrogen cycle.


Assuntos
Bentonita , Herbicidas/isolamento & purificação , Resíduos Industriais , Solo , Diquat/isolamento & purificação , Paraquat/isolamento & purificação , Pirazóis/isolamento & purificação , Vinho
9.
Rev Sci Instrum ; 78(5): 055103, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17552856

RESUMO

An experimental device for making isobaric heat capacity measurements of liquids under pressure is presented. The device is an adaptation of the Setaram micro-DSC II atmospheric-pressure microcalorimeter, including modifications of vessels and a pressure line allowing the pressure in the measurement system to be set, controlled, and stabilized. The high sensitivity of the apparatus combined with a suitable calibration procedure allows very accurate heat capacity measurements under pressure to be made. The relative uncertainty in the isobaric molar heat capacity measurements provided by the new device is estimated to be 0.08% at atmospheric pressure and 0.2% at higher levels. The device was validated from isobaric molar heat capacity measurements for hexane, nonane, decane, undecane, dodecane, and tridecane, all of which were highly consistent with reported data. It also possesses a high sensitivity as reflected in its response to changes in excess isobaric molar heat capacity with pressure, which were examined in this work for the first time by making heat capacity measurements throughout the composition range of the 1-hexanol+n-hexane system. Finally, preliminary measurements at several pressures near the critical conditions for the nitromethane+2-butanol binary system were made that testify to the usefulness of the proposed device for studying critical phenomena in liquids under pressure.


Assuntos
Varredura Diferencial de Calorimetria/instrumentação , Soluções/química , Transdutores , Varredura Diferencial de Calorimetria/métodos , Desenho de Equipamento , Análise de Falha de Equipamento , Pressão , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
11.
Phys Rev E Stat Nonlin Soft Matter Phys ; 71(4 Pt 1): 041503, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15903673

RESUMO

The viscosity near the critical point in nitrobenzene+hexane and nitrobenzene+heptane binary systems was studied by examining the viscosity values for critical mixtures at a variable temperature as obtained with a falling-ball viscometer. The regular part of the viscosity of the critical mixtures was calculated by interpolating measurements made at noncritical concentrations. Because viscosity anomaly studies must be conducted at zero shear, a method allowing the estimation of the effective shear for this type of viscometer was developed with a view to introducing the corrections required. This methodology was used to determine the critical exponent for the viscosity anomaly in nitrobenzene+hexane and nitrobenzene+heptane systems, which were found to be 0.0422+/-0.0004 and 0.0432+/-0.0013 , respectively, very consistent with the accepted value: 0.043.

12.
Qual Life Res ; 13(3): 587-99, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15130023

RESUMO

OBJECTIVE: To investigate associations between health-related quality of life (HRQoL), as assessed using the multidimensional quality of life-HIV (MQOL-HIV) questionnaire, and adherence to antiretroviral treatment in HIV-infected subjects. DESIGN: Multicentre cross-sectional study in three institutional tertiary hospitals in northwest Spain. PATIENTS AND METHODS: The MQOL-HIV was completed by 235 HIV-infected adults undergoing antiretroviral treatment. Adherence to antiretroviral therapy was assessed by using patient's self-report. Information about sociodemographic characteristics and clinical variables was also collected. RESULTS: Good adherence (> or = 95% of prescribed pills correctly taken) was reported by 131 patients (55.7%). Univariate analyses indicated that the sociodemographic and clinical variables associated with adherence were age, educational level, income, employment, home stability, transmission route, history of previous antiretroviral therapy, and number of prescribed pills/day. Subscales of MQOL-HIV associated with adherence were mental health, cognitive functioning, financial status, medical care, partner intimacy, and (in men only) sexual functioning. Stepwise logistic regression showed that good adherence was more frequent in patients aged > 40 years (odds ratio, OR: 2.50; 95% confidence interval, CI: 1.15-5.61) and in patients with high cognitive functioning (OR: 2.26; 95% CI: 1.19-4.30). Conversely, poor adherence was more frequent in patients without stable home (OR: 2.96; 95% CI: 1.39-6.32), in patients required to take 14 or more pills/day (OR: 2.17; 95% CI: 1.18-4.28), in patients with low financial status (OR: 3.42; 95% CI: 1.57-7.45), and in patients reporting low medical care (OR: 2.07; 95% CI: 1.07-3.98). CONCLUSIONS: HRQoL dimensions, notably cognitive functioning, financial status and medical care, are closely associated with antiretroviral therapy adherence.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Cooperação do Paciente/estatística & dados numéricos , Qualidade de Vida/psicologia , Autoadministração/psicologia , Adulto , Fatores Etários , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente/psicologia , Autoavaliação (Psicologia) , Perfil de Impacto da Doença , Espanha
13.
Hepatogastroenterology ; 50(54): 2093-7, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14696471

RESUMO

BACKGROUND/AIMS: HBV, HCV, and HIV have some transmission routes in common. Viral liver disease is a leading cause of mortality in HIV-infected patients. The study was aimed at evaluating the prevalence of HBV and HCV markers in subjects with different risk practices for HIV infection. METHODOLOGY: A total of 699 subjects were studied Of these subjects, 517 were intravenous drug users (373 HIV-positive and 144 HIV-negative), 127 had heterosexual risk practice (66 HIV-positive and 61 HIV-negative), 31 had homosexual risk practice (all HIV-positive), 15 had post-transfusional HIV infection, and nine had HIV infection of unknown source. Patients with anti-HBc antibody were considered HBV-positive, and cases with anti-HCV antibodies were considered HCV-positive. RESULTS: Among patients with HIV infection, most intravenous drug users (79%) had markers of both HBV and HCV, compared with 20%, 11%, and 10% of cases infected by transfusional, heterosexual, and homosexual route, respectively (p < 0.001). Absence of both HBV and HCV markers was observed in most HIV-positive heterosexuals (62%) compared with 40% of post-transfusional cases, 32% of homosexuals and 4% of intravenous drug users (p: NS, p = 0.009, and p < 0.001, respectively). Isolated HBV-positivity was the most frequent pattern in HIV-infected homosexuals (58%), compared with 27% of post-transfusional, 21% of heterosexuals and 11% of intravenous drug users (p: NS, p < 0.001 and p < 0.001, respectively). HIV-negative intravenous drug users had a lower prevalence of HBV/HCV association than HIV-positive cases (p < 0.001). Isolated HCV-positivity was more frequent in HIV-negative than in HIV-positive intravenous drug users (27% vs. 6%, p < 0.001). In heterosexuals, isolated HBV-positivity was more prevalent in HIV-positive than in HIV-negative cases (21% vs. 7%, p = 0.04). CONCLUSIONS: HBV and HCV seroprevalence in HIV infected patients vary depending on the risk practice. This suggests a variable transmissibility depending on the route considered. Within the same risk practice, differences in HCV and HBV seroprevalence between HIV-positive and HIV-negative cases suggest that some factors associated with HIV infection may influence the rate of infection by HCV and HBV.


Assuntos
Soropositividade para HIV/epidemiologia , Hepatite B/transmissão , Hepatite C/transmissão , Assunção de Riscos , Abuso de Substâncias por Via Intravenosa/epidemiologia , Adolescente , Adulto , Idoso , Transfusão de Sangue/estatística & dados numéricos , Comorbidade , Feminino , Soropositividade para HIV/sangue , Hepatite B/sangue , Anticorpos Anti-Hepatite B/sangue , Hepatite C/sangue , Anticorpos Anti-Hepatite C/sangue , Homossexualidade Masculina/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Sexo Seguro , Espanha/epidemiologia , Abuso de Substâncias por Via Intravenosa/sangue
14.
Rev Neurol ; 37(3): 267-74, 2003.
Artigo em Espanhol | MEDLINE | ID: mdl-12938059

RESUMO

OBJECTIVES: This review focuses on the dietary treatment of four neuropediatric disorders: 1) X-linked adrenoleukodystrophy (X-ALD); 2) attention deficit disorders (ADD); 3) refractory epilepsy; and 4) inborn errors of metabolism. DEVELOPMENT: The use of Lorenzo's oil in the treatment of X-ALD has been controversial since no clear efficacy has been demonstrated because of a lack of controlled studies. Although this treatment normalizes the levels of very-long chain fatty acids in children with the cerebral form of X-ALD, the neurological symptoms persist or progress. The dietary treatment of ADD with or without hyperactivity consists of elimination diets such as the Feingold diet and megavitamins. Although the results of several controlled studies are contradictory, there is no scientific evidence that sugar, artificial food colorings or sweeteners are responsible for behavior or learning problems in children. The ketogenic diet has been effective for the control of refractory epilepsy such as infantile spasms and myoclonic seizures. Important side effects include gastrointestinal complaints, metabolic complications, poor growth and nutrition, liver abnormalities and renal calculi. The early identification and treatment of inborn errors of metabolism require prompt diagnosis and correction of metabolic abnormalities. Restriction of protein and fats may be necessary in certain neurometabolic disorders. A variety of special formulas is available to meet the nutritional requirements and avoid offending substances in neurometabolic patients. CONCLUSIONS: Dietary treatment plays an important role in the management of certain neuropediatric disorders, such as the use of special formulas in inborn errors of metabolism and the ketogenic diet in refractory epilepsy. The efficacy of Lorenzo's oil in the cerebral form of X-ALD and of the elimination of artificial food colorings and sweeteners in ADD remain to be proved.


Assuntos
Adrenoleucodistrofia/terapia , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Dieta , Epilepsia/terapia , Erros Inatos do Metabolismo/terapia , Adrenoleucodistrofia/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Criança , Combinação de Medicamentos , Epilepsia/fisiopatologia , Ácidos Erúcicos/uso terapêutico , Humanos , Erros Inatos do Metabolismo/fisiopatologia , Trioleína/uso terapêutico
15.
Phys Rev E Stat Nonlin Soft Matter Phys ; 66(3 Pt 1): 031507, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12366120

RESUMO

The heat capacity per unit volume C(p) and density rho of the nitromethane-1-butanol critical mixture near its upper consolute point are determined in this work. C(p) data are obtained at atmospheric pressure as a function of temperature in the one-phase and two-phase regions, using a differential scanning calorimeter. The suitability of DSC for recording C(p) as a function of T in the critical region is confirmed by measurements of the nitromethane-cyclohexane mixture, the results being quite consistent with reported data. By fitting the C(p) data in the one-phase region, the critical exponent alpha is found to be 0.110+/-0.014-and hence consistent with the universal accepted value-and the critical amplitude A(+)=0.0606+/-0.0006 J K(-1) cm(-3). Rho data were only obtained in the one-phase region, using a vibrating tube densimeter. The amplitude of the density anomaly was found to be C(+)(1)=-0.017+/-0.003 g cm(-3), which is moderately low in spite of the large difference between the densities of the pure liquids. The thermodynamic consistency of the A+ and C+1 values was examined in relation to the previously reported value for the slope of the critical line dT(c)/dp. The results of this analysis were consistent with previous work on this matter.

16.
Blood ; 98(8): 2389-95, 2001 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-11588035

RESUMO

Tristetraprolin (TTP) is a member of the CCCH tandem zinc-finger class of proteins. It can bind to and destabilize mRNAs encoding tumor necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Conversely, mice deficient in TTP develop a complex syndrome characterized by cachexia, myeloid hyperplasia, and joint and skin inflammation. Studies using anti-TNF-alpha neutralizing antibodies demonstrated that this syndrome, at least in part, is a consequence of the excess production of TNF-alpha in the absence of TTP. To evaluate the role played by each TNF-alpha receptor in the pathogenesis of this syndrome, mice were generated that were deficient in TTP and either or both of the known TNF-alpha receptors (TNFRs), type 1 (TNFR1) and type 2 (TNFR2). Mice deficient in TTP and TNFR1, or in TTP and both receptors, were protected from developing the TNF-alpha-induced cachexia and inflammation. In contrast, mice deficient in TNFR2 were more severely affected than mice deficient in TTP alone, suggesting that TNFR2 might play a protective role in the development of the syndrome. In cultured cells derived from these mice, apparent cooperation between the TNFRs was required to achieve normal TNF-alpha-induced expression of TTP, TNF-alpha, and GM-CSF mRNAs. Finally, the results showed that TNFR1 plays an important role in mediating TNF-alpha-induced changes in TNF-alpha and GM-CSF mRNA stability.


Assuntos
Proteínas de Ligação a DNA , Proteínas Imediatamente Precoces/fisiologia , Receptores do Fator de Necrose Tumoral/fisiologia , Animais , Antígenos CD/genética , Antígenos CD/fisiologia , Células da Medula Óssea/citologia , Células Cultivadas , Regulação da Expressão Gênica , Triagem de Portadores Genéticos , Humanos , Proteínas Imediatamente Precoces/deficiência , Proteínas Imediatamente Precoces/genética , Macrófagos/citologia , Camundongos , Camundongos Knockout , RNA Mensageiro/genética , Receptores do Fator de Necrose Tumoral/classificação , Receptores do Fator de Necrose Tumoral/deficiência , Receptores do Fator de Necrose Tumoral/genética , Receptores Tipo I de Fatores de Necrose Tumoral , Receptores Tipo II do Fator de Necrose Tumoral , Síndrome , Transcrição Gênica , Tristetraprolina , Fator de Necrose Tumoral alfa/genética , Dedos de Zinco
17.
J Biol Chem ; 276(45): 42580-7, 2001 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-11546803

RESUMO

Treatment of macrophages with pyridinyl imidazole inhibitors of p38 protein kinases can inhibit lipopolysaccharide-stimulated tumor necrosis factor alpha secretion. However, bone marrow-derived macrophages from tristetraprolin (TTP)-deficient mice were less sensitive than normal macrophages to this effect of p38 inhibitors, despite evidence for normal p38 activation in response to lipopolysaccharide. TTP is known to cause decreased stability of tumor necrosis factor alpha and granulocyte-macrophage colony-stimulating factor mRNAs after binding to an AU-rich element in their 3'-untranslated regions. A recombinant TTP fusion protein could be phosphorylated by a recombinant p38 kinase in cell-free assays and was phosphorylated to the same extent by immunoprecipitated p38 derived from normal and TTP-deficient cells stimulated with lipopolysaccharide; in both cases, the enzyme activity was inhibited by the p38 inhibitors. TTP phosphorylation also was increased in intact macrophages after lipopolysaccharide stimulation, an effect that was blocked by the p38 inhibitors. Finally, TTP in mammalian cell extracts bound less well to an AU-rich element RNA probe than did the same amount of TTP following dephosphorylation. These results suggest that TTP may be a component of the signaling cascade, initiated by inflammatory stimuli and mediated in part by activation of p38, that ultimately leads to enhanced secretion of tumor necrosis factor alpha.


Assuntos
Proteínas de Ligação a DNA , Inibidores Enzimáticos/farmacologia , Proteínas Imediatamente Precoces/fisiologia , Proteínas Quinases Ativadas por Mitógeno/fisiologia , Regiões 3' não Traduzidas/metabolismo , Animais , Interleucina-3/genética , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Fosforilação , RNA Mensageiro/análise , Proteínas Recombinantes de Fusão/metabolismo , Tristetraprolina , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genética , Proteínas Quinases p38 Ativadas por Mitógeno
18.
EMBO J ; 20(14): 3760-70, 2001 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-11447117

RESUMO

Interleukin-10 (IL-10) is a key inhibitory signal of inflammatory responses that regulates the production of potentially pathogenic cytokines like tumor necrosis factor (TNF). We show here that the development of chronic intestinal inflammation in IL-10-deficient mice requires the function of TNF, indicating that the IL-10/TNF axis regulates mucosal immunity. We further show that IL-10 targets the 3' AU-rich elements (ARE) of TNF mRNA to inhibit its translation. Moreover, IL-10 does not alter TNF mRNA stability, and its action does not require the presence of the stability-regulating ARE binding factor tristetraprolin, indicating a differential assembly of stability and translation determinants on the TNF ARE. Inhibition of TNF translation by IL-10 is exerted mainly by inhibition of the activating p38/MAPK-activated protein kinase-2 pathway. These results demonstrate a physiologically significant cross-talk between the IL-10 receptor and the stress-activated protein kinase modules targeting TNF mRNA translation. This cross-talk is necessary for optimal TNF production and for the maintenance of immune homeostasis in the gut.


Assuntos
Interleucina-10/metabolismo , Intestinos/patologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Biossíntese de Proteínas/fisiologia , RNA Mensageiro/genética , Fator de Necrose Tumoral alfa/genética , Animais , Separação Celular , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Interleucina-10/genética , Interleucina-10/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Proteínas Serina-Treonina Quinases/metabolismo , Especificidade por Substrato , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/biossíntese , Proteínas Quinases p38 Ativadas por Mitógeno
19.
Ginecol Obstet Mex ; 69: 346-50, 2001 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-11816531

RESUMO

Although the use of prostaglandin plays an important role in the reproductive human physiology, it is still controversial in the reproductive field. Ovarian stimulation as well as intrauterine insemination increased the reproductive goals in certain group of patients. The objective of the present study was to evaluate the prostaglandin effect (misoprostol) in patients under ovarian stimulation and intrauterine insemination and their final outcome in the clinical pregnancy rate. There were a total of 59 ovarian stimulated cycles, the study group (n = 29) received 200 micrograms of prostaglandin E1 (misoprostol) intravaginal after IUI, compared with the control group (n = 30). Demographic characteristics were similar in both groups. There were no differences in age, FSH. LH and E2, hCG day and number of ampoules between groups. However, a significant pregnancy rate was observed between groups (31% study group vs. 20% control group). We concluded that prostaglandin application in stimulated cycles under intrauterine insemination remain a beneficial effect showing in the pregnancy outcome.


Assuntos
Inseminação Artificial , Misoprostol/farmacologia , Ocitócicos/farmacologia , Taxa de Gravidez , Administração Intravaginal , Adulto , Intervalos de Confiança , Interpretação Estatística de Dados , Feminino , Humanos , Misoprostol/administração & dosagem , Indução da Ovulação , Ocitócicos/administração & dosagem , Gravidez , Estudos Prospectivos , Fatores de Tempo
20.
J Biol Chem ; 275(23): 17827-37, 2000 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-10751406

RESUMO

Macrophages derived from tristetraprolin (TTP)-deficient mice exhibited increased tumor necrosis factor alpha (TNFalpha) release as a consequence of increased stability of TNFalpha mRNA. TTP was then shown to destabilize TNFalpha mRNA after binding directly to the AU-rich region (ARE) of the 3'-untranslated region of the TNFalpha mRNA. In mammals and in Xenopus, TTP is the prototype of a small family of three known zinc finger proteins containing two CCCH zinc fingers spaced 18 amino acids apart; a fourth more distantly related family member has been identified in Xenopus and fish. We show here that representatives of all four family members were able to bind to the TNFalpha ARE in a cell-free system and, in most cases, promote the breakdown of TNFalpha mRNA in intact cells. Because the primary sequences of these CCCH proteins are most closely related in their tandem zinc finger domains, we tested whether various fragments of TTP that contained both zinc fingers resembled the intact protein in these assays. We found that amino- and carboxyl-terminal truncated forms of TTP, as well as a 77 amino acid fragment that contained both zinc fingers, could bind to the TNFalpha ARE in cell-free cross-linking and gel shift assays. In addition, these truncated forms of TTP could also stimulate the apparent deadenylation and/or breakdown of TNFalpha mRNA in intact cells. Alignments of the tandem zinc finger domains from all four groups of homologous proteins have identified invariant residues as well as group-specific signature amino acids that presumably contribute to ARE binding and protein-specific activities, respectively.


Assuntos
Regiões 3' não Traduzidas/metabolismo , Proteínas de Ligação a DNA , Proteínas Imediatamente Precoces , Proteínas de Membrana/metabolismo , Fatores de Terminação de Peptídeos/metabolismo , Proteínas/metabolismo , RNA Mensageiro/química , RNA Mensageiro/metabolismo , Proteínas de Saccharomyces cerevisiae , Proteínas de Xenopus , Dedos de Zinco , Regiões 3' não Traduzidas/química , Sequência de Aminoácidos , Animais , Sequência de Bases , Linhagem Celular , Evolução Molecular , Humanos , Proteínas de Membrana/química , Camundongos , Dados de Sequência Molecular , Fatores de Terminação de Peptídeos/química , Filogenia , Proteínas/química , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Transfecção , Tristetraprolina , Xenopus
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