RESUMO
El asma afecta entre 100 y 150 millones de personas en el mundo. En la actualidad, esta enfermedad se puede controlar por diversas terapias, pero no se puede curar y representa una de las enfermedades más costosas y frecuentes en los sistemas de salud en muchos países, por lo que son necesarias estrategias de prevención eficientes para reducir la morbimortalidad y costos económicos; esto requiere, entre otros, de un conocimiento detallado de los mecanismos inmunológicos y fisiológicos involucrados en el asma. Esta revisión sintetiza el conocimiento sobre la inflamación mediada por T H2 en asma y se discute el origen d elas células CD4+ T H'2 y el papel de las citocinas T H2 en la producción y mantenimiento de la inflamación de las vías respiratorias en esta enfermedad.
Asthma affects between 100 and 150 million people around the globe. Currently, it is a disease that can be controlled by diverse therapeutic approaches; unfortunately, it cannot be cured. In many countries asthma is one of the most expensive and frequent diseases for the healthcare systems. Therefore, effective preventive strategies are greatly needed to reduce individual morbidity, mortality and economic burdens. This requires, among others, a detailed knowledge of the immunoiogicai and physiological mechanisms involved in asthma. This review synthesizes our understanding about the inflammation of T H2-mediated asthma and discusses the origin of CD4 + T H2 cells and the role of T H2 cytokines in producing and maintaining airway inflammation in asthma.
RESUMO
Diabetes mellitus is a disease characterized by impaired glucose metabolism that leads to retinopathy, brain micro-infarcts and other complications. We have previously shown that oral glycine administration to diabetic rats inhibits non-enzymatic glycation of hemoglobin and diminishes renal damage. In this work, we evaluated the capacity of the amino acid glycine (1% w/v, 130 mM) to attenuate diabetic complications in streptozotocin (STZ)-induced diabetic Wistar rats and compared them with non-treated or taurine-treated (0.5% w/v, 40 mM) diabetic rats. Glycine-treated diabetic rats showed an important diminution in the percentage of animals with opacity in lens and microaneurysms in the eyes. Interestingly, there was a diminished expression of O-acetyl sialic acid in brain vessels compared with untreated diabetic rats (P<0.05). Additionally, peripheral blood mononuclear cells isolated from glycine-treated diabetic rats showed a better proliferative response to PHA or ConA than those obtained from non-treated diabetic rats (P<0.05). Glycine-treated rats had a less intense corporal weight loss in comparison with non-treated animals. Our results suggest that administration of glycine attenuates the diabetic complications in the STZ-induced diabetic rat model, probably due to inhibition of the non-enzymatic glycation process.
Assuntos
Aneurisma/prevenção & controle , Artérias Cerebrais/patologia , Diabetes Mellitus Experimental/complicações , Angiopatias Diabéticas/prevenção & controle , Glicina/administração & dosagem , Administração Oral , Aneurisma/patologia , Animais , Artérias Cerebrais/efeitos dos fármacos , Angiopatias Diabéticas/patologia , Hemoglobinas Glicadas/metabolismo , Glicosilação/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Taurina/administração & dosagemRESUMO
BACKGROUND: Hyperglycemia induces protein glycation, disturbing its function, additionally, the glycated products (AGEs) induce by themselves proinflammatory cytokine release that are responsible for insulin resistance. Glycine has been successfully used in diabetic patients to competitively reduce hemoglobin glycation. OBJECTIVES: To assess hyperglycemia impact on the immune response and to evaluate if it is possible to reverse it by means of glycine administration. MATERIAL AND METHODS: Streptozotocin-induced diabetic rats, with and without glycine administration were challenged with sheep red blood cells, and specific antibody producing cells were accounted. Normal rats were challenged as controls. RESULTS: Induced diabetes modifies significantly the humoral immune response capacity versus sheep red blood cells. Also, glycine administration prevents against this deleterious effect. CONCLUSIONS: Glycine could be an important therapeutic resource among diabetics to avoid the characteristic immunodeficiencies of this disease.
Assuntos
Formação de Anticorpos/efeitos dos fármacos , Diabetes Mellitus Experimental/imunologia , Glicina/uso terapêutico , Síndromes de Imunodeficiência/tratamento farmacológico , Animais , Células Produtoras de Anticorpos/efeitos dos fármacos , Células Produtoras de Anticorpos/imunologia , Glicemia/análise , Diabetes Mellitus Experimental/complicações , Avaliação Pré-Clínica de Medicamentos , Eritrócitos/imunologia , Hemoglobinas Glicadas/análise , Produtos Finais de Glicação Avançada/análise , Glicina/farmacologia , Síndromes de Imunodeficiência/etiologia , Masculino , Ratos , Ratos Wistar , Ovinos , EstreptozocinaRESUMO
The study investigated the mechanism by which glycine protects against increased circulating nonesterified fatty acids (NEFA), fat cell size, intra-abdominal fat accumulation, and blood pressure (BP) induced in male Wistar rats by sucrose ingestion. The addition of 1% glycine to the drinking water containing 30% sucrose, for 4 wk, markedly reduced high BP in sucrose-fed rats (SFR) (122.3 +/- 5.6 vs. 147.6 +/- 5.4 mmHg in SFR without glycine, P < 0.001). Decreases in plasma triglyceride (TG) levels (0.9 +/- 0.3 vs. 1.4 +/- 0.3 mM, P < 0.001), intra-abdominal fat (6.8 +/- 2.16 vs. 14.8 +/- 4.0 g, P < 0.01), and adipose cell size were observed in SFR treated with glycine compared with SFR without treatment. Total NEFA concentration in the plasma of SFR was significantly decreased by glycine intake (0.64 +/- 0.08 vs. 1.11 +/- 0.09 mM in SFR without glycine, P < 0.001). In control animals, glycine decreased glucose, TGs, and total NEFA but without reaching significance. In SFR treated with glycine, mitochondrial respiration, as an indicator of the rate of fat oxidation, showed an increase in the state IV oxidation rate of the beta-oxidation substrates octanoic acid and palmitoyl carnitine. This suggests an enhancement of hepatic fatty acid metabolism, i.e., in their transport, activation, or beta-oxidation. These findings imply that the protection by glycine against elevated BP might be attributed to its effect in increasing fatty acid oxidation, reducing intra-abdominal fat accumulation and circulating NEFA, which have been proposed as links between obesity and hypertension.
Assuntos
Tecido Adiposo/citologia , Sacarose Alimentar , Ácidos Graxos não Esterificados/sangue , Glicina/farmacologia , Sacarose/farmacologia , Tecido Adiposo/efeitos dos fármacos , Animais , Tamanho Celular/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar , Sacarose/administração & dosagemRESUMO
Inadequate utilization of glucose in diabetes mellitus favors diverse metabolic alterations that play a relevant role in the physio-pathology of chronic complications of this disease. Streptozotocin-induced diabetic rats were treated daily with glycine (130 mM as optimal concentration) or taurine (40 mM) for six months. Groups of diabetic rats without treatment were used as controls. Glucose, total cholesterol, triacylglycerol, and glycated hemoglobin were determined periodically after inducing diabetes. Rats were killed after 6 months of treatment and histological analyses were performed. Diabetic groups that received glycine or taurine showed significant lower concentrations of glucose, total cholesterol, triacylglycerol, and glycated hemoglobin than diabetic control rats (P<0.05) after 6 months treatment. Histological analyses of diabetic rats showed pancreatic atrophy and necrosis, vacuolization, decrease of beta cells, and diffuse glomerulosclerosis. Diabetic rats treated with glycine or taurine showed less enlargement of the glomerular basal membrane than control diabetic rats. Our results suggest that glycine and taurine reduced the alterations induced by hyperglycemia in streptozotocin-induced diabetic rats probably due to inhibition of oxidative processes.
Assuntos
Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Glicina/uso terapêutico , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Colesterol/sangue , Diabetes Mellitus Experimental/patologia , Glicina/farmacologia , Masculino , Ratos , Ratos WistarRESUMO
La distribución espacial de los grupos en un fármaco puede influir tanto en su actividad biológica como en su naturaleza química, por lo que es necesario resolver las mezclas racémicas de los nuevos fármacos para poder establecer si existe diferencia en la actividad farmacológica o en la toxicidad de sus estereoisómeros. En este trabajo se describe la resolución del racemato antiepiléptico (ñ)-HEPA, para lo cual se sintetizaron las sales diasteroeméricas de quinina del ácido 2-hidroxi, 2-etil, 2-fenil acético, se recristalizaron con etanol y su tratamiento con ácido sulfúrico concentrado liberó los ácidos ópticamente activos. La a 20º D del ácido dextrorrotatorio fue + 32.6º en agua, mientras que la correspondiente al ácido levorrotatorio fue -23.43º en agua. Este último se esterificó con metanol y el tratamiento del éster con amoniaco produjo la (+)-HEPA con a 20º D = + 10.71º en acetona
Assuntos
Acetamidas/farmacocinética , Amidas/química , Anticonvulsivantes/farmacologia , Epilepsia/terapia , Farmacocinética , Farmacologia , EstereoisomerismoRESUMO
En 1962 sintetizamos una serie de nuevos fármacos originalmente planeados como inhibidores de la transaminasa del ácido-aminobutírico-ácido-cetoglutárico, mediante la sustitución de los átomos de hidrógeno del carbono gamma de la molécula cíclica del ácido gamma aminobutírico por los grupos etilo y fenilo, metilo y fenilo y difenilo. Los estudios de resonancia magnética y de difracción de rayos X revelaron que estos compuestos son fenilalcoholamidas. En una serie de estudios farmacológicos, electrofisiológicos y de comportamiento, así como estudios clínicos preliminares, la DL-4-hidroxi, 4-etil, 4-fenil butiramida (HEPB) demostró poseer una actividad anticonvulsionante poderosa. Por lo tanto, hemos sintetizado los homólogos propionamida y acetamida del HEPB con la meta de obtener anticonvulsionantes más potentes y menos tóxicos. La caracterización de estos compuestos se está llevando a cabo mediante los esfuerzos de un progama multidisciplinario de varios grupos de investigación en diferentes instituciones mexicanas
Assuntos
Anticonvulsivantes/farmacocinética , Butiratos/farmacocinética , Epilepsia/terapia , Ácido gama-Aminobutírico/química , Farmacocinética , FarmacologiaRESUMO
Se estudió el efecto inhibidor del aminoácido glicina sobre la glicosilación no enzimática de la hemoglobina en la diabetes experimental de ratas Wistar con estreptozotocina. La hemoglobina glicosilada de las ratas diabéticas fue de 4.2 ñ 0.38 por ciento y la de las diabéticas que tomaron glicina al 1 por ciento en el agua de bebida ad libitum fue de 2.90 ñ 0.37 por ciento (p = 0.00005). Un grupo de 30 personas diabéticas tipo II y 8 de tipo I tomaron glicina disuelta en agua: 20 gramos diarios (4 tomas de 5 g cada 6 horas) durante tiempos variables: de 3 hasta 56 meses. La hemoglobina glicosilada promedio de los diabéticos antes de tomar la clicina fue de 12.8 ñ 3.3 por ciento y después fue de 8.3 ñ 2.2 por ciento con un valor de p= 7 x 10-12 (prueba de rangos señalados de Wilcoxon)