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1.
Immunotherapy ; 12(1): 9-24, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31914828

RESUMO

Aim: Glucose intolerance associates with M1/M2 macrophage unbalance. We thus wanted to examine the effect of M2 macrophage administration on mouse model of glucose intolerance. Materials & methods: C57BL/6 mice fed a high-fat diet (HFD) for 12 weeks and then received thrice 20 mg/kg streptozotocin (HFD-GI). Bone marrow-derived stem cells were collected from donor mice and differentiated/activated into M2 macrophages for intraperitoneal administration into HFD-GI mice. Results: M2 macrophage treatment abolished glucose intolerance independently of obesity. M2 macrophage administration increased IL-10 in visceral adipose tissue and serum, but showed no effect on serum insulin. While nitric oxide synthase-2 and arginase-1 remained unaltered, M2 macrophage treatment restored AKT phosphorylation in visceral adipose tissue. Conclusion: M2 macrophage treatment abolishes glucose intolerance by increasing IL-10 and phosphorylated AKT.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Imunoterapia/métodos , Interleucina-10/metabolismo , Macrófagos/imunologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Diabetes Mellitus Tipo 2/imunologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Intolerância à Glucose , Humanos , Resistência à Insulina , Interleucina-10/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais , Estreptozocina , Células Th2/imunologia
2.
Clin Exp Med ; 16(2): 193-202, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-25894568

RESUMO

Morbid obesity has been shown to increase the risk to develop hepatic steatosis, also referred to as non-alcoholic fatty liver disease (NAFLD). Emerging evidence suggests that the severity of NAFLD may associate with increased serum levels of inflammatory markers as well as decreased concentration of mediators with anti-inflammatory actions, such as tumor necrosis factor alpha (TNF-α) and interleukin (IL) 10, respectively. We thus examined the serum levels of TNF-α and IL-10 in 102 morbidly obese women and men (body mass index > 40 kg/m(2)), exhibiting different grades of NAFLD. Blood glucose, glycated hemoglobin, insulin, the homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol, triglycerides, high- and low-density lipoproteins, parameters of liver function, TNF-α, and IL-10 were measured in each subject. The stage of NAFLD was estimated by abdominal ultrasound imaging. In comparison with morbidly obese subjects without steatosis, morbidly obese patients with NAFLD showed increased age (39.23 ± 9.80 years), HOMA-IR (6.74 ± 1.62), total cholesterol (219.7 ± 9.58 mg/dl), aspartate aminotransferase (36.25 ± 3.24 UI/l), gamma-glutamyl transpeptidase (37.12 ± 3.41 UI/l), and TNF-α (37.41 ± 1.72 pg/ml) as well as decreased serum levels of IL-10 (61.05 ± 2.43 pg/ml). Interestingly, the systemic levels of TNF-α increased, while IL-10 decreased in accordance with the severity of NAFLD, which supports a role for systemic inflammatory mediators in promoting steatosis progression. Further clinical prospective studies need to be addressed to elucidate the role of TNF-α and IL-10 in the development of NAFLD while also establishing their clinical utility in the assessment of morbidly obese patients at higher risk to develop severe steatosis.


Assuntos
Interleucina-10/sangue , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade Mórbida/complicações , Soro/química , Fator de Necrose Tumoral alfa/sangue , Adolescente , Adulto , Idoso , Feminino , Humanos , Fígado/diagnóstico por imagem , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Ultrassonografia , Adulto Jovem
3.
J Rheumatol ; 42(4): 630-7, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25512480

RESUMO

OBJECTIVE: Patients with juvenile-onset spondyloarthritis (SpA) may develop ankylosis of the midfoot resembling the spinal changes seen in patients with ankylosing spondylitis (AS). The study of the histopathology of the feet of patients with tarsitis could help us understand the pathogenesis of bone formation in affected structures in the SpA. The objective of our study was to describe the histopathologic characteristics of the midfoot in patients with tarsitis associated with SpA. METHODS: We obtained synovial sheaths, entheses, and bone samples from 20 patients with SpA with midfoot pain/tenderness and swelling. Tissue samples underwent H&E staining; immunohistochemistry for CD3, CD4, CD8, CD68, and CD20 cell identification; and immunofluorescence for bone lineage proteins, including osteocalcin, osteopontin, parathyroid hormone-related protein, bone sialoprotein, and alkaline phosphatase. RESULTS: Slight edema and hyalinization were found in some tendon sheaths, and few inflammatory cells were detected in the entheses. In bones, we found some changes suggesting osteoproliferation, including endochondral and intramembranous ossification, but no inflammatory cells. In entheses showing bone proliferation, we detected osteocalcin and osteopontin in cells with a fibroblast-mesenchymal phenotype, suggesting the induction of entheseal cells toward an osteoblast phenotype. CONCLUSION: Osteoproliferation and abnormal expression of bone lineage proteins, but no inflammatory infiltration, characterize midfoot involvement in patients with SpA. In this sense, tarsitis (or ankylosing tarsitis) resembles the involvement of the spine in patients with AS. Ossification may be in part explained by the differentiation of mesenchymal entheseal cells toward the osteoblastic lineage.


Assuntos
Anquilose/metabolismo , Pé/patologia , Sialoproteína de Ligação à Integrina/metabolismo , Osteocalcina/metabolismo , Osteopontina/metabolismo , Proteína Relacionada ao Hormônio Paratireóideo/metabolismo , Espondilartrite/metabolismo , Adulto , Fosfatase Alcalina/metabolismo , Anquilose/patologia , Biomarcadores/metabolismo , Osso e Ossos/metabolismo , Estudos Transversais , Feminino , Humanos , Masculino , Espondilartrite/patologia , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia , Adulto Jovem
4.
Rev. Fac. Med. UNAM ; 54(5): 2-3, sep.-oct. 2011.
Artigo em Espanhol | LILACS | ID: biblio-956889
5.
Rev. Fac. Med. UNAM ; 54(2): 10-20, mar.-abr. 2011. ilus
Artigo em Espanhol | LILACS | ID: biblio-956863

RESUMO

La amibiasis es un padecimiento que afecta al 10% de la población mundial, y puede tener un comportamiento muy diverso, tanto en el intestino como en diversos órganos (hígado, pulmones, cerebro, piel). Se conoce su ciclo biológico, los síntomas y signos de su penetración al organismo, así como su diagnóstico y tratamiento, pero aún hay controversias sobre los mecanismos moleculares de la patogenicidad de la E. Histolítica, para lo cual se ha utilizado en particular el absceso hepático experimental en Hamsters (AHAH). Durante mucho tiempo se sostuvo que la patogenicidad de E. Histolítica se debía a su capacidad para destruir tejidos, pero encontramos que la E. Histolítica virulenta, per se es incapaz de causar daño al hígado del hámster leucopénico. Este estudio se dedicó a estudiar los mecanismos de virulencia de la amiba mediante la comparación funcional y molecular entre E. Histolítica virulenta y E. Histolítica no virulenta. Encontramos que la virulencia de este parásito no se puede explicar solamente por la actividad de sus moléculas citotóxicas (adhesinas, fosfolipasas y ameboporos) o proteolíticas (proteasas), y los hallazgos sugieren que cuando las amibas virulentas arriban al hígado del hámster y se encuentran una concentración tóxica de oxígeno, éste las sensibiliza a la lisis por el complemento, el peróxido de hidrógeno y el ácido hipocloroso. Las consecuencias de estos hallazgos pueden abrir nuevas perspectivas para el diseño de terapias alternativas para el tratamiento de este padecimiento.


Amoebiasis is a disease that affects 10 % of the world population, and it may have a different behavior when attacks bowels, liver, lungs, brain, etc. Its biological cycle is well known, as well as its symptoms and signs of its penetration into those organs, its diagnosis and treatment, but it is still a controversy on the molecular mechanism of its pathogenesis; to study them it, the experimental hepatic abscess in hamsters has been employed. For years it was considered that the pathogenicity of E. Histolítica was due to its capacity to destroy tissues, but we found that virulent E. Histoliticaperse is unable to produce liver damage in leucopenic hamster; we therefore studied the mechanisms of virulence of the amoeba by functional and molecular comparison between virulent and non virulent E. Histolitica. We found that the parasit virulence cannot be explained only by the activity of citotoxic or proteolytic molecules (adhesines, phospholypases and amebopores, or proteases), and the findings suggest that when amoebas arrives to the hamster liver and find a toxic concentration of oxygen, this sensibilizes them to lysis by complement, hydrogen peroxide and hypoclorose acid. The consequences of those findings may open new perspectives for the design of new therapies for the treatment of this disease.

6.
PLoS One ; 5(4): e10231, 2010 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-20422055

RESUMO

BACKGROUND: Senescent cells occur in adults with cirrhotic livers independent of the etiology. AIM: Investigate the presence rate of cellular senescence and expression of cell cycle check points in livers from children with end stage disease. METHODOLOGY/PRINCIPAL FINDINGS: Livers of five children aged three years or less undergoing liver transplantation due to tyrosinemia (n = 1), biliary atresia (n = 2), or fulminant hepatitis (n = 2) were analyzed for senescence associated beta-galactosidase (SA-betagal) activity and p16INK4a, p21cip1 and p53. All livers displayed positive cellular staining for SA-betagal in the canals of Hering and interlobular biliary ducts. In the presence of cirrhosis (3/5 cases) SA-betagal was found at the cholangioles and hepatocytes surrounding the regenerative nodules. Children with fulminant hepatic failure without cirrhosis had significant ductular transformation with intense SA-betagal activity. No SA-betagal activity was evident in the fibrous septa. Staining for p53 had a similar distribution to that observed for SA-betagal. Staining for p16(INK4a) and p21(cip1) was positive in the explanted liver of the patient with tyrosinemia, in the hepatocytes, the canals of Hering, cholangioles and interlobular bile ducts. In the livers with fulminant hepatitis, p21(cip1) staining occurred in the areas of ductular transformation and in the interlobular bile ducts. CONCLUSIONS/SIGNIFICANCE: Cellular senescence in livers of children with end stage disease is associated with damage rather than corresponding to an age dependent phenomenon. Further studies are needed to support the hypothesis that these senescence markers correlate with disease progression.


Assuntos
Senescência Celular , Falência Hepática/etiologia , Falência Hepática/patologia , Atresia Biliar , Criança , Inibidor p16 de Quinase Dependente de Ciclina/análise , Inibidor de Quinase Dependente de Ciclina p21/análise , Humanos , Fígado/patologia , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Falência Hepática Aguda , Transplante de Fígado , Proteína Supressora de Tumor p53/análise , Tirosinemias
7.
Int J Parasitol ; 39(6): 693-702, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19073188

RESUMO

Entamoeba histolytica virulence has been attributed to several amoebic molecules such as adhesins, amoebapores and cysteine proteinases, but supporting evidence is either partial or indirect. In this work we compared several in vitro and in vivo features of both virulent E. histolytica (vEh) and non-virulent E. histolytica (nvEh) axenic HM-1 IMSS strains, such as complement resistance, proteinase activity, haemolytic, phagocytic and cytotoxic capacities, survival in mice caecum, and susceptibility to O(2). The only difference observed was a higher in vitro susceptibility of nvEh to O(2). The molecular mechanism of that difference was analyzed in both groups of amoebae after high O(2) exposure. vEh O(2) resistance correlated with: (i) higher O(2) reduction (O(2)(-) and H(2)O(2) production); (ii) increased H(2)O(2) resistance and thiol peroxidase activity, and (iii) reversible pyruvate: ferredoxin oxidoreductase (PFOR) inhibition. Despite the high level of carbonylated proteins in nvEh after O(2) exposure, membrane oxidation by reactive oxygen species was not observed. These results suggest that the virulent phenotype of E. histolytica is related to the greater ability to reduce O(2) and H(2)O(2) as well as PFOR reactivation, whereas nvEh undergoes irreversible PFOR inhibition resulting in metabolic failure and amoebic death.


Assuntos
Entamoeba histolytica/fisiologia , Entamoeba histolytica/patogenicidade , Oxigênio/metabolismo , Oxigênio/toxicidade , Estresse Fisiológico , Animais , Peróxido de Hidrogênio/metabolismo , Camundongos , Oxirredução , Peroxidase/metabolismo , Piruvato Sintase/antagonistas & inibidores , Superóxidos/metabolismo , Virulência
8.
Exp Parasitol ; 116(3): 257-65, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17336295

RESUMO

Apoptosis has been described in some parasites like Leishmania, Trypanosoma, and Trichomonas. This phenomenon has not been observed yet in Entamoeba histolytica. This work analyzed the in vitro effect of sodium nitroprusside, sodium nitrite and sodium nitrate (NOs) on E. histolytica apoptosis. Parasites incubated for 1h with NOs revealed apoptosis 6h later (95% viability), demonstrated by YOPRO-1, TUNEL, DNA fragmentation and low ATP levels. The caspase inhibitor Z-VAD-FMK inhibited total intracellular cysteine protease activity (CPA) but had no effect on apoptosis. When treated with NOs some amebic functions like complement resistance and hemolytic activity decreased but CPA and erythrophagocytosis remained unchanged. After treatment in vitro with NOs, parasite death was almost complete at 24h; but when injected into hamster livers they disappeared in less than 6h. These results show that apoptosis is induced in vitro by NOs in E. histolytica and renders them incapable of surviving in hamster's livers.


Assuntos
Apoptose/efeitos dos fármacos , Entamoeba histolytica/efeitos dos fármacos , Óxido Nítrico/farmacologia , Animais , Cricetinae , Fragmentação do DNA , Entamoeba histolytica/citologia , Entamoeba histolytica/fisiologia , Marcação In Situ das Extremidades Cortadas , Abscesso Hepático Amebiano/parasitologia , Masculino , Mesocricetus , Microscopia Confocal , Nitratos/farmacologia , Doadores de Óxido Nítrico/farmacologia , Nitroprussiato/farmacologia , Nitrito de Sódio/farmacologia
9.
Arch Med Res ; 37(2): 203-9, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16380320

RESUMO

Classical descriptions of the pathology of amebiasis portray the parasite as the cause of tissue damage and destruction, and in recent years a number of amebic molecules have been identified as virulence factors. In this review we describe a series of experiments that suggest a more complex host-parasite relation, at least during the early stages of acute experimental amebic liver abscess in hamsters. The problems of extrapolating experiments in vitro to explain observations in vivo are discussed. The role of amebic cysteine proteases is examined and evidence presented to suggest that they are primarily related not to tissue damage but to amebic survival, which is required for the progression of the lesion. Inflammation is shown to be not only the major cause of tissue damage but also an absolute requirement for amebic survival in the liver, whereas complement and ischemia are not involved in the disappearance of the parasite in the absence of inflammation.


Assuntos
Entamoeba histolytica/patogenicidade , Abscesso Hepático Amebiano/fisiopatologia , Animais , Cricetinae , Abscesso Hepático Amebiano/parasitologia
11.
Rev. invest. clín ; Rev. invest. clín;57(2): 170-176, mar.-abr. 2005.
Artigo em Espanhol | LILACS | ID: lil-632468

RESUMO

A discussion of four aspects of the legislation and of the medical ethics of the transplants is presented: the concept of death, the donation of organs, the selection of receivers and the future of the therapeutic transplants. The prominent paragraphs of the General Law of Health of the country about cerebral death, the two legal forms and organs donors' ethics, the criteria and more frequent problems for the selection of receivers, and the character of medical technology of transition of the therapeutic transplants are included.


Se presenta una discusión de cuatro aspectos de la legislación y de la ética médica de los transplantes: el concepto de muerte, la donación de órganos, la selección de receptores y el futuro de los trasplantes terapéuticos. Se incluyen los párrafos relevantes de la Ley General de Salud del país sobre muerte cerebral, las dos formas legales y éticas de donadores de órganos, los criterios y problemas más frecuentes para la selección de receptores, y el carácter de tecnología médica de transición de los trasplantes terapéuticos.


Assuntos
Adulto , Criança , Humanos , Transplante , Transplante/legislação & jurisprudência , Morte Encefálica/diagnóstico , Cadáver , Mercantilização , Morte , Diagnóstico Diferencial , Doação Dirigida de Tecido , Previsões , Parada Cardíaca , Direitos Humanos , Consentimento Livre e Esclarecido , Cuidados para Prolongar a Vida , México , Propriedade , Seleção de Pacientes , Estado Vegetativo Persistente/diagnóstico , Doadores de Tecidos , Coleta de Tecidos e Órgãos , Coleta de Tecidos e Órgãos/legislação & jurisprudência , Obtenção de Tecidos e Órgãos , Obtenção de Tecidos e Órgãos/legislação & jurisprudência
12.
Rev. Inst. Nac. Enfermedades Respir ; Rev. Inst. Nac. Enfermedades Respir;18(1): 9-11, ene.-mar. 2005. ilus
Artigo em Espanhol | LILACS | ID: lil-632632
14.
Parasitol Res ; 90(3): 212-20, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12783310

RESUMO

Amebic cysteine protease 2 (EhCP2) was purified from ethyl ether extracts of axenically grown trophozoites of Entamoeba histolytica strain HM1-IMSS. The purification procedure involved molecular filtration and electroelution. Sequence analysis of the purified product revealed EhCP2 and ubiquitin(s). Electrophoretic migration patterns, isoelectric point determination and Western blot studies failed to reveal other EhCP molecules. Polyclonal antibodies against the purified EhCP2 prepared in rabbits either stabilized or enhanced the enzyme activity in a dose-response manner. Purified EhCP2 was enclosed within inert resin microspheres (22-44 microm in diameter) and injected into the portal vein of normal hamsters. In the liver, the microspheres caused mild acute inflammation and occasional minimal necrosis of short duration. Sections of the liver were immunohistochemically stained with the anti-EhCP2 antibody and the microspheres were positive for only a very short period (1 h) after injection. Sections of experimental acute (1 day, 5 days) amebic liver abscess produced in hamsters were also stained with the anti-EhCP2 antibody; and amebas were intensely positive but no staining was observed at any time in the surrounding necrotic structures. It is suggested that EhCP2 plays either a minor or no role in the causation of tissue damage in experimental acute liver amebiasis.


Assuntos
Cisteína Endopeptidases/metabolismo , Entamoeba histolytica/patogenicidade , Entamebíase/patologia , Abscesso Hepático Amebiano/patologia , Doença Aguda , Animais , Cricetinae , Cisteína Endopeptidases/isolamento & purificação , Entamoeba histolytica/enzimologia , Entamebíase/parasitologia , Fígado/enzimologia , Fígado/patologia , Abscesso Hepático Amebiano/parasitologia , Coelhos
15.
Med. interna Méx ; 17(5): 242-249, sept.-oct. 2001.
Artigo em Espanhol | LILACS | ID: lil-314327
16.
Salud pública Méx ; 43(4): 368-372, jul.-ago. 2001. CD-ROM
Artigo em Espanhol | LILACS | ID: lil-309586

RESUMO

En el contexto de una intervención en el Foro de Consulta Democrática de la Coordinación de los Institutos Nacionales de Salud sobre Enseñanza e Investigación en Salud, realizado en el Instituto Nacional de Cardiología Ignacio Chávez, se hace una revisión crítica de la clasificación convencional de la ciencia en básica y aplicada; además, se analiza lo que deberían ser la enseñanza y la investigación en salud. Para apoyar su propia clasificación de la ciencia en "bien hecha", la cual "genera conocimientos verificables sobre la realidad" y la "mal hecha", improductiva o productora de "puras mentiras" y "no debe patrocinarse", el autor revisa las definiciones utilitaristas y peyorativas como las que establecen ciencia comprometida y ciencia pura, ciencia útil y ciencia inútil, y ciencia práctica y ciencia esotérica, como sinónimos de ciencia aplicada y ciencia básica y afirma que, en México, esta diferenciación "para lo único que ha servido en el pasado es para justificar la reducción en el apoyo oficial a la ciencia básica, porque no estaba dirigida a resolver los problemas nacionales o porque no caía en las prioridades establecidas en ese sexenio". En cuanto a educación e investigación en salud reconoce que el programa actual de formación de investigadores tiene una eficiencia muy baja y propone un estudio científico crítico, realizado por un equipo de especialistas, interdisciplinario, "para integrar la carrera del investigador científico desde la captura de la juventud inteligente hasta la jubilación o muerte del investigador" y para el cual la evaluación de la eficiencia del apoyo a sus proyectos de investigación no se restrinja a si se publicó o no un artículo "pues la calidad del trabajo científico y la contribución de un investigador al desarrollo de la ciencia no es nada más el número de sus publicaciones". El texto completo en inglés de este artículo está disponible en: http://www.insp.mx/salud/index.html


Assuntos
Apoio à Pesquisa como Assunto , Ciência , Tecnologia , Pesquisa/economia , Apoio Financeiro , México , Projetos de Pesquisa/tendências
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