RESUMEN
PURPOSE: Both type 2 diabetes (T2D) and low levels of high-density lipoprotein cholesterol (HDL-C) are very prevalent conditions among Mexicans. Genetic variants in the LIPC gene have been associated with both conditions. This study aimed to evaluate the association of the -514C < T (rs1800588) LIPC gene polymorphism with different metabolic traits, particularly the effects of this polymorphism on HDL-C plasma levels and T2D risk. METHODS: Mediation analysis was used to assess the direct and indirect effects of the -514C>T LIPC gene variant on HDL-C levels, T2D risk, and body mass index (BMI), in 2105 Mexican mestizo participants. We also assessed the functional effect of the -514C>T LIPC variant on the promoter activity of a reporter gene in the HepG2 cell line. RESULTS: Direct effects show that the -514C>T LIPC polymorphism is significantly associated with increased HDL-C plasma levels (ß = 0.03; p < 0.001). The -514C>T variant resulted in an indirect protective effect on T2D risk through increasing HDL-C levels (ß = - 0.03; p < 0.001). Marginal direct association between -514C>T and T2D was found (ß = 0.08; p = 0.06). Variables directly influencing T2D status were European ethnicity (ß = - 7.20; p < 0.001), age (ß = 0.04; p < 0.001), gender (ß = - 0.15; p = 0.017) and HDL-C (ß = - 1.07; p < 0.001). In addition, we found that the -514C>T variant decreases the activity of LIPC promoter by 90% (p < 0.001). CONCLUSIONS: The -514C>T polymorphism was not directly associated with T2D risk. HDL-C acts as a mediator between -514C>T LIPC gene variant and T2D risk in the Mexican population.
Asunto(s)
Biomarcadores/sangre , Índice de Masa Corporal , HDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/epidemiología , Lipasa/genética , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patología , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Adulto JovenRESUMEN
PURPOSE: Type 2 diabetes (T2D) and low serum concentration of high-density lipoprotein cholesterol (HDL-c) are common coexisting metabolic disorders. ABCA1 variants have been shown to be associated to these conditions. We sought to test the combined effect of two ABCA1 gene common variants, rs2422493 (- 565C > T) and rs9282541 (R230C) on HDL-c levels and T2D risk. METHODS: Path analysis was conducted in 3,303 Mexican-mestizos to assess the specific contributions of rs2422493 and rs9282541 ABCA1 variants, insulin resistance, waist-to-height ratio (WHtR), and age on HDL-c levels and T2D risk. Participants were classified into four groups according to their ABCA1 variants carrier status: (i) the reference group carried wild type alleles for both ABCA1 variants (-/-), (ii) +/- were carriers of rs2422493 but non-carriers of rs9282541, (iii) -/+ for carriers of rs9282541 but not carriers of rs2422493 and (iv) carriers of minor alleles for both SNPs (+/+). Principal components from two previous genome-wide association studies were used to control for ethnicity. RESULTS: We identified significant indirect effects on T2D risk mediated by HDL-c in groups -/+ and +/+ (ß = 0.04; p = 0.03 and ß = 0.06; p < 0.01, respectively) in comparison to the -/- reference group. Low concentrations of HDL-c were directly and significantly associated with increased T2D risk (ß = -0.70; p < 0.01). WHtR, male gender, age, and insulin resistance were also associated with T2D risk (p < 0.05). There was no significant direct effect for any of the ABCA1 groups on T2D risk: p = 0.99, p = 0.58, and p = 0.91 for groups +/-, -/+, and +/+ respectively. CONCLUSIONS: The ABCA1 rs9282541 (R230C) allele is associated with T2D in Mexicans through its effect on lowering HDL-c levels. This is the first report demonstrating that HDL-c levels act as an intermediate factor between an ABCA1 variant and T2D.
Asunto(s)
Transportador 1 de Casete de Unión a ATP/genética , HDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/epidemiología , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Adulto , Biomarcadores/análisis , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/genética , Femenino , Estudios de Seguimiento , Estudio de Asociación del Genoma Completo , Humanos , Masculino , México/epidemiología , Persona de Mediana Edad , PronósticoRESUMEN
A combination of three different Salmonella-specific bacteriophages (BPs) and one competitive exclusion (CE) product were used to reduce Salmonella Enteritidis (SE) colonization in experimentally infected chickens. Equal numbers of 7-day-old chickens were used in each of three groups: a CE group (treated with CE), a BP group (treated with BP), and a CE-plus-BP group (treated with both products). The CE product was administered via coarse spray at 1 day of age and the cocktail of three BPs was given via spray at 6 days of age using a multiplicity of infection of 10(3) plaque-forming units. All the experimental groups, except a healthy control group, were challenged orally with 2.95 x 10(5) colony-forming units (CFU)/ml of an SE strain at 7 days of age. Seven days postchallenge, the chickens were euthanatized for individual SE detection, quantitative bacteriology, and phage isolation from ceca and an internal organ pool. The qualitative bacteriology demonstrated that the use of the CE product diminished the incidence of SE to 75.7% and the mixture of BPs reduced it to 80%; when CE plus BP were used, the incidence dropped significantly to 38.7% (P < 0.0001), as compared with the infection control group (100%). A significant difference in the incidence was observed between the CE and the CE-plus-BP groups, and the BP and the CE-plus-BP groups (P = 0.0027 and P = 0.0010, respectively). The mean SE cecal count diminished with the use of CE plus BP (1.6 x 10(2) CFU/g, P = 0.0003) compared with the control group (1.56 x 10(5) CFU/g), the CE group (4.23 x 10(3) CFU/g), and the BP group (9.48 x 10(3) CFU/g). On the basis of the present study, it may be concluded that the use of both types of biocontrollers can be an effective method for reducing SE colonization in commercial chickens, but further basic and applied research is needed.
Asunto(s)
Pollos , Enfermedades de las Aves de Corral/prevención & control , Probióticos , Salmonelosis Animal/prevención & control , Fagos de Salmonella/fisiología , Salmonella enteritidis/virología , Aerosoles , AnimalesRESUMEN
Three different lyric bacteriophages (BPs) were isolated from the sewage system of commercial chicken flocks and used to reduce Salmonella Enteritidis (SE) colonization from experimental chickens. Ten-day-old chickens were challenged with 9.6 x 10(5) colony-forming units (CFU)/ml of a SE strain and treated by coarse spray or drinking water with a cocktail of the three phages at a multiplicity of infection (MO1) of 10(3) plaque-forming units (PFU) 24 hr prior to SE challenge. Chickens were euthanatized at day 20 of age for individual SE detection, quantitative bacteriology, and phage isolation from the intestine and from a pool of organs. SE detection was performed by both bacteriologic culture and genome detection by polymerase chain reaction (PCR). Qualitative bacteriology showed that aerosol-spray delivery of BPs significantly reduced the incidence of SE infection in the chicken group (P = 0.0084) to 72.7% as compared with the control group (100%). In addition, SE counts showed that phage delivery both by coarse spray and drinking water reduced the intestinal SE colonization (P < 0.01; P < 0.05, respectively). BPs were isolated at 10 days postinfection from the intestine and from pools of organs from BP-treated chickens. We conclude that the phage treatment, either by aerosol spray or drinking water, may be a plausible alternative to antibiotics for the reduction of Salmonella infection in poultry.
Asunto(s)
Portador Sano/veterinaria , Pollos/microbiología , Enfermedades de las Aves de Corral/prevención & control , Salmonelosis Animal/prevención & control , Fagos de Salmonella/fisiología , Salmonella/virología , Animales , Portador Sano/prevención & controlRESUMEN
OBJECTIVE: To determine the impact of pregnancy on systemic lupus erythematosus (SLE) outcome. METHODS: SLE patients, age >or=16 yrs, disease duration Asunto(s)
Lupus Eritematoso Sistémico
, Complicaciones del Embarazo
, Trastornos Puerperales/etiología
, Adulto
, Negro o Afroamericano/estadística & datos numéricos
, Métodos Epidemiológicos
, Femenino
, Hispánicos o Latinos/estadística & datos numéricos
, Humanos
, Lupus Eritematoso Sistémico/etnología
, Embarazo
, Complicaciones del Embarazo/etnología
, Resultado del Embarazo
, Trastornos Puerperales/etnología
, Puerto Rico/epidemiología
, Índice de Severidad de la Enfermedad
, Factores Socioeconómicos
, Estados Unidos/epidemiología
, Población Blanca/estadística & datos numéricos
RESUMEN
Listeria monocytogenes es un patógeno emergente que se adquiere por el consumo de alimentos contaminados, como carnes crudas. El objetivo es relevar la presencia de Listeria monocytogenes en carne vacuna fresca en el área del Gran Mendoza. Se analizaron 100 muestras de carne molida común, adquiridas en supermercados (78 por cento) y carnicerías (22 por cento). Las muestras se preenriquecieron en caldo UVM I y se enriquecieron en caldo UVM II. El aislamiento se realizó en Agar Palcam. Las colonias con características diferenciales de Listeria fueron prrificadas en TSAYE. Para identificarlas, se les realizaron a cada una los siguientes tests: Reacción de Gram positiva, catalasa positiva, movilidad en medio SIM a 30ºC, hemólisis en Agar sangre, test de CAMP, fermentación de carbohidratos y reducción de nitratos. En total se aislaron 306 colonias, de las cuales 68 cepas se identificaron como Listeria monocytogenes El 37 por cento de las muestras de carne dieron positivas para Listeria monocytogenes.
Asunto(s)
Contaminación de Alimentos , Listeria monocytogenes , CarneRESUMEN
The authors' objective was to determine by 2-dimensional echo Doppler (2DECHO) the cardiac abnormalities in juvenile onset ankylosing spondylitis (JOAS) and adult onset ankylosing spondylitis (AOAS) in male patients with long-term disease. Twenty patients with JOAS, 31 with AOAS, and 20 healthy controls of the same age and gender without cardiopulmonary symptoms were studied. Using 2DECHO, the heart dimensions were determined according to American Society of Echocardiography guidelines. The left ventricle ejection fraction (LVEF) was calculated by Teichholz's formula. Cardiomyopathy was established when 2DECHO had diminished LVEF. Statistics used were the Student t and Fisher test, chi2, and ANOVA. Ninety percent of JOAS and 51% of AOAS patients were B27+ (p=0.005). The disease duration was 19.3 +/- 8.8 years in JOAS and 14.8 +/- 12.8 years in AOAS (p=NS). Age at the time of the study was 30.7 +/- 9.9 years in JOAS vs 40.3 +/- 12.7 in AOAS (p=0.003), and vs 40.2 +/- 17 years in controls (p=NS). There was a higher frequency of cardiomyopathy in AOAS (32.2%) than in JOAS (25%) and the controls (0%) (p=0.01). Patients with JOAS had a higher mitral valve gradient (25%) than AOAS patients (19%, p=NS) and controls (0%, p=0.04). Abnormal aortic ring reflectance was shown in 19% of AOAS vs 0% abnormalities in JOAS and controls (p=0.01). The aortic root diameter was increased in 58% of AOAS, 30% of JOAS, and 0% of controls (p=0.001). The frequency of 2DECHO abnormalities was increased in cardiopulmonary asymptomatic spondylitis patients. Despite the high frequency of B27+, JOAS had a lower frequency of aortic abnormalities than AOAS. Mitral valve gradient was found in JOAS and in AOAS that could contribute to a decreased ejection fraction and to left ventricular dysfunction.
Asunto(s)
Ecocardiografía Doppler/métodos , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Espondilitis Anquilosante/complicaciones , Disfunción Ventricular Izquierda/diagnóstico por imagen , Adolescente , Adulto , Distribución por Edad , Edad de Inicio , Análisis de Varianza , Válvula Aórtica/diagnóstico por imagen , Niño , Preescolar , Intervalos de Confianza , Enfermedades de las Válvulas Cardíacas/epidemiología , Enfermedades de las Válvulas Cardíacas/etiología , Humanos , Incidencia , Masculino , Válvula Mitral/diagnóstico por imagen , Valores de Referencia , Medición de Riesgo , Sensibilidad y Especificidad , Espondilitis Anquilosante/epidemiología , Disfunción Ventricular Izquierda/epidemiología , Disfunción Ventricular Izquierda/etiologíaRESUMEN
The objective of this study was to investigate possible defects in the insulin sensitivity and/or the acute insulin response in a group of Mexican patients displaying early-onset type 2 diabetes and to evaluate the contribution of mutations in three of the genes linked to maturity-onset diabetes of the young. We studied 40 Mexican patients with an age of diagnosis between 20 and 40 yr in which the insulin sensitivity as well as the insulin secretory response were measured using the minimal model approach. A partial screening for possible mutations in 3 of the 5 genes linked to maturity-onset diabetes of the young was carried out by PCR-single strand conformation polymorphism analysis. A low insulin secretory capacity (AIRg = 68.5 +/- 5 muU/mL.min) and a near-normal insulin sensitivity (3.43 +/- 0.2 min/muU.mL x 10(4)) were found in these patients. Among this group we found two individuals carrying missense mutations in exon 4 of the hepatocyte nuclear factor-1alpha (HNF-4alpha) gene (Asp(126)-->His/Tyr and Arg(154)-->Gln, respectively) and one carrying a nonsense mutation in exon 7 of the HNF-1alpha gene (Gln(486)-->stop codon); 7.5% had positive titers for glutamic acid decarboxylase antibodies. Thirty-five percent of cases had insulin resistance; these subjects had the lipid abnormalities seen in the metabolic syndrome. A defect in insulin secretion is the hallmark in Mexican diabetic patients diagnosed between 20 and 40 yr of age. Mutations in either the HNF-1alpha or the HNF-4alpha genes are present among the individuals who develop early-onset diabetes in our population. These particular sequence changes have not been previously reported and therefore represent putative new mutations. Even in the absence of endogenous hyperinsulinemia, insulin resistance is associated with an adverse lipid profile.
Asunto(s)
Proteínas de Unión al ADN , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/genética , Proteínas Nucleares , Adulto , Edad de Inicio , Anticuerpos/análisis , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Glucoquinasa/genética , Glutamato Descarboxilasa/inmunología , Factor Nuclear 1 del Hepatocito , Factor Nuclear 1-alfa del Hepatocito , Factor Nuclear 1-beta del Hepatocito , Factor Nuclear 4 del Hepatocito , Humanos , Insulina/metabolismo , Resistencia a la Insulina , Secreción de Insulina , Lipoproteínas/sangre , Masculino , México , Persona de Mediana Edad , Mutación , Linaje , Fosfoproteínas/genética , Factores de Transcripción/genéticaRESUMEN
Symptomatic and asymptomatic astrovirus infection was prospectively determined in a 3-year birth cohort of Mayan infants. Stool samples from 271 infants and 268 older siblings were tested for astrovirus, adenovirus 40/41, rotavirus and Salmonella, Shigella and Campylobacter species. Concurrent diarrhea, vomiting, fever, or anorexia were noted. Astrovirus was detected in 164 infants (61%) and 20 siblings (7%). Rotavirus (4%) and adenovirus 40/41 (13%) were isolated less frequently. Of all diarrheal episodes reported at a visit, 26% (78/305) were associated with astrovirus; 17% (78/452) of astrovirus infections were associated with diarrhea and 9% with other symptoms. Only diarrhea was associated with astrovirus infection (odds ratio, 1.4; 95% confidence interval [CI], 1.07-1.92; P = .01). Of infants with astrovirus, 70% shed at multiple visits over a period of 2-17 weeks (median, 5). The point prevalence of astrovirus infection was significantly higher among infants than siblings (relative risk, 6.18; 95% CI, 3.93-9.72; P < .0001, chi2). Astrovirus was identified throughout the year, peaked in March and May, and decreased in September. In this population, astrovirus was the most common enteric pathogen isolated; symptomatic infection was prevalent among infants.
Asunto(s)
Infecciones por Astroviridae/epidemiología , Astroviridae , Indígenas Centroamericanos , Población Rural , Infecciones por Adenoviridae/diagnóstico , Infecciones por Adenoviridae/inmunología , Astroviridae/genética , Astroviridae/inmunología , Infecciones por Astroviridae/inmunología , Infecciones por Astroviridae/fisiopatología , Infecciones por Astroviridae/virología , Infecciones por Campylobacter/diagnóstico , Estudios de Cohortes , Diarrea Infantil/epidemiología , Diarrea Infantil/virología , Disentería Bacilar/diagnóstico , Heces/microbiología , Heces/virología , Humanos , Lactante , México/epidemiología , Prevalencia , Estudios Prospectivos , Infecciones por Rotavirus/diagnóstico , Infecciones por Rotavirus/inmunología , Infecciones por Salmonella/diagnóstico , Estaciones del AñoRESUMEN
Steroid 21-hydroxylase deficiency is the underlying cause in over 90% of patients with congenital adrenal hyperplasia, an inherited metabolic disorder of adrenal steroidogenesis. We have characterized 94 mutant alleles from 47 unrelated Mexican patients and the corresponding mutant alleles in their parents by amplification of the functional CYP21 gene by PCR, followed by direct sequence analysis. The study included patients diagnosed with the three clinical forms of the disease. Our results revealed: (1) the presence of relatively few mutations or combinations of mutations associated with particular phenotypes; (2) the presence of putative new mutations; (3) the finding of identical genotypes in patients displaying discordant phenotypes; (4) the identification of patients lacking all previous reported mutations; and (5) an apparent high frequency of germ-line mutations. The absence of previously reported mutations in about 22% of the disease alleles, the finding of putative new mutations in some of the patients lacking previously known mutations, and the apparent high prevalence of germ-line mutations make evident the differences in the genetic background leading to this disorder between the Caucasian and the Mexican populations.
Asunto(s)
Hiperplasia Suprarrenal Congénita , Hiperplasia Suprarrenal Congénita/genética , Mutación de Línea Germinal , Mutación Puntual , Esteroide 21-Hidroxilasa/genética , Hiperplasia Suprarrenal Congénita/enzimología , Hiperplasia Suprarrenal Congénita/epidemiología , Análisis Mutacional de ADN , Femenino , Pruebas Genéticas , Genotipo , Humanos , Masculino , México/epidemiología , Reacción en Cadena de la Polimerasa , Prevalencia , Análisis de Secuencia de ADNRESUMEN
3-Nitropropionic acid (3-NPA) was identified as the toxic component of several plants and fungi. Recently, it was described that 3-NPA produced hypotension, accompanied by a paradoxical bradycardia. In this study, we identified a possible mechanism of action, explaining the effect of 3-NPA on cardiac tissue. We used isolated, spontaneously beating atria and heart mitochondria to measure electrophysiological properties and mitochondrial oxygen consumption. We also measured Na+/K+ ATPase activity and intracellular ATP levels. In isolated spontaneously beating atria, 3-NPA (10(-4) M) decreased heart rate by 62 +/- 3%. This agent did not affect the amplitude or duration of action potentials. The duration of intervals between two action potentials, however, was prolonged from 530 +/- 285 to 1400 +/- 600 ms after 3-NPA exposure (10(-2) M). Oxygen consumption by heart mitochondria was inhibited by 3-NPA when either malate/glutamate or succinate were used as metabolism substrates. Cytochrome C oxidase activity was not affected by 3-NPA. Finally, atrial ATP content decreased 65 +/- 3% after 3-NPA treatment. In conclusion, we show that 3-NPA decreases atrial rate by increasing the action potential phase 4, probably by inhibition of mitochondrial respiration, thereby decreasing cardiac ATP content. This suggests that 3-NPA-induced bradycardia may be related to intracellular ATP depletion.
Asunto(s)
Antihipertensivos/toxicidad , Bradicardia/inducido químicamente , Atrios Cardíacos/efectos de los fármacos , Mitocondrias Cardíacas/efectos de los fármacos , Propionatos/toxicidad , Adenosina Trifosfato/metabolismo , Animales , Bradicardia/fisiopatología , Complejo IV de Transporte de Electrones/metabolismo , Electrofisiología , Atrios Cardíacos/enzimología , Atrios Cardíacos/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Mitocondrias Cardíacas/metabolismo , Nitrocompuestos , Técnicas de Cultivo de Órganos , Oxígeno/metabolismo , Consumo de Oxígeno , Ratas , Ratas Wistar , ATPasa Intercambiadora de Sodio-Potasio/metabolismoRESUMEN
The occurrence of Yersinia enterocolitica in tonsils and rectal swabs from 100 healthy pigs and the rectal swabs of 100 healthy cattle slaughtered at Santiago-Chile were analysed. Yersinia enterocolitica was isolated from 48 (48%) pigs but not from cattle. 98.2% of strains were of 4/O3 bioserogroup, considered to be pathogenic for humans. All of the strains were resistant to penicillin producing beta-lactamase. Most of them were resistant to neomicin and tetracycline. The pYV marker was used to demonstrate pathogenicity in all strains by four different assays: 65.5% of the strains were pYV positive by their plasmid profile; 73.3% by crystal violet binding; 84.5% by calcium dependency and 87.9% by hybridization with probe associated with cytotoxicity to Hep-2 cells in vitro. All of the Yersinia enterocolitica strains were pYV positive with at least one of the four tests analysed, 46/58 strains were positive by three tests simultaneously. The similarities between associated cytotoxic genes of porcine and human strains is discussed. The phenotypic and genotypic characteristics demonstrated by the isolates strains suggest that the pigs in Chile are reservoir of potential pathogenic Yersinia enterocolitica for humans.
Asunto(s)
Bovinos/microbiología , Porcinos/microbiología , Yersinia enterocolitica , Animales , Portador Sano/veterinaria , Chile , Electroforesis/veterinaria , Plásmidos/aislamiento & purificación , Yersinia enterocolitica/clasificación , Yersinia enterocolitica/efectos de los fármacos , Yersinia enterocolitica/genética , Yersinia enterocolitica/aislamiento & purificaciónRESUMEN
Steroid 21-hydroxylase deficiency is caused by mutations in the CYP21 gene. Approximately 95% of mutant alleles are generated by recombination events between the active gene CYP21 and its highly homologous pseudogene, CYP21P. Deletion alleles are generated by unequal crossing over, while point mutations are the result of gene conversion events. Deletions account for 20-25% of the 21-hydroxylase deficiency alleles in most populations studied. We have looked for deletions among 53 unrelated Mexican patients with steroid 21-hydroxylase deficiency and found that deletions represent less than 1% of the disease alleles. These findings suggest that nearly all mutant alleles in our patient population contain point mutations and that the low representation of deletion alleles among clinically diagnosed patients may be due to missing detection of salt wasters, mainly males, who may die during the neonatal period.
Asunto(s)
Proteínas Bacterianas , Eliminación de Gen , Esteroide 21-Hidroxilasa/genética , Hiperplasia Suprarrenal Congénita , Alelos , Secuencia de Bases , Southern Blotting , ADN/metabolismo , ADN Polimerasa Dirigida por ADN/metabolismo , Desoxirribonucleasas de Localización Especificada Tipo II/metabolismo , Frecuencia de los Genes , Heterocigoto , Humanos , México , Datos de Secuencia Molecular , Polimerasa TaqRESUMEN
1. We have shown that nonsteroidal anti-inflammatory drugs are potent inhibitors of neutrophil activation. Tenoxicam is a new compound of the oxicam family which has been shown to be effective for routine clinical use. 2. In the present study we examined the immune pharmacological effects of this compound on lymphocyte function by determining its effect on the expression of IL-2 receptors, on monocyte function by looking at chemotaxis and IL-1 release and on neutrophil function by evaluating the chemotactic response to a standard stimulus. 3. The data show that Tenoxicam inhibits the neutrophil and monocyte functional chemotactic response in vitro, and to some extent in vivo for monocytes, but has no effect on the expression of IL-2 receptors or IL-1 release. Tenoxicam inhibits the mobilization of neutrophils and monocytes to inflammatory sites, even though this effect was not clearly demonstrable when cells were tested after oral use.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Linfocitos/efectos de los fármacos , Monocitos/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Piroxicam/análogos & derivados , Receptores de Interleucina-2/metabolismo , Quimiotaxis/efectos de los fármacos , Humanos , Técnicas In Vitro , Linfocitos/metabolismo , Monocitos/metabolismo , Neutrófilos/metabolismo , Piroxicam/farmacologíaRESUMEN
Purified IgG from BALB/c mouse anti-C3H serum exerts positive inotropic and chronotropic effects in C3H mouse atria and induces testosterone synthesis in C3H mouse Leydig cells. The effect depends on IgG concentration and can be abolished by beta-adrenergic-receptor and luteinizing hormone-receptor antagonists. IgG interferes with the binding of dihydroalprenolol and luteinizing hormone. Monoclonal antibodies against major histocompatibility complex class I antigens were active on the Leydig cells of C3H and BALB/c mice. There was a parallelism between the effect of each individual monoclonal antibody with specificity for a particular haplotype and the response of the target cell from the strains carrying such haplotypes. These antibodies could precipitate the soluble luteinizing hormone-receptor complex. The results suggested that bound hormone triggers the association of major histocompatibility class I antigen with the receptor, thereby activating the respective target cells.
Asunto(s)
Antígenos de Histocompatibilidad , Receptores Adrenérgicos beta/fisiología , Receptores de HL/fisiología , Animales , Anticuerpos Monoclonales/fisiología , Función Atrial , Membrana Celular/fisiología , Gonadotropina Coriónica/metabolismo , Dihidroalprenolol/metabolismo , Frecuencia Cardíaca , Antígenos de Histocompatibilidad/inmunología , Sueros Inmunes , Inmunización , Alotipos de Inmunoglobulinas , Inmunoglobulina G/fisiología , Técnicas de Inmunoadsorción , Isoproterenol/farmacología , Células Intersticiales del Testículo/inmunología , Células Intersticiales del Testículo/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Contracción Miocárdica , Propranolol/farmacología , Receptores de HL/inmunología , Testosterona/biosíntesisRESUMEN
We studied the involvement of major histocompatibility (MHC) class I antigens on the mechanism of LH/hCG receptor activation. For this purpose we investigated the effects of anti-MHC class I antibodies on hormone-receptor interaction, signal transduction, and MHC class I antigen-receptor interaction. Monoclonal antibodies against MHC class I antigen were able to stimulate testosterone production in mouse Leydig cells with the same potency as LH. This biological effect depends on the concentration of antibody used and could be abolished by a LH antagonist. There is a perfect parallelism, for each monoclonal antibody, between the specificity for a particular haplotype and the response of the target cells from the strains carrying such a haplotype. The same antibodies were able to precipitate the soluble LH/hCG receptors, as both a hormone-receptor complex and a free receptor. The results suggest that bound hormone triggers an association of the MHC class I antigen with the LH/hCG receptor, resulting in activation of the target cell.
Asunto(s)
Antígenos HLA/inmunología , Hormona Luteinizante/inmunología , Receptores de HL/inmunología , Animales , Anticuerpos , Anticuerpos Monoclonales , Células Intersticiales del Testículo/inmunología , Células Intersticiales del Testículo/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Receptores de HL/fisiología , Testosterona/biosíntesisRESUMEN
Aldosterone secretion from adrenal glomerulosa cells can be stimulated by angiotensin II (AII), extracellular potassium and adrenocorticotropin (ACTH). Since the mitochondria can recognize factors generated by AII (cyclic-AMP-independent) and ACTH (cyclic AMP dependent), it is reasonable to postulate the existence of a common intermediate in spite of a different signal transduction mechanism. We have evaluated this hypothesis by stimulation of mitochondria from glomerulosa gland with fractions isolated from glomerulosa gland stimulated with AII or from fasciculata gland stimulated with ACTH; the same fractions were tested using mitochondria from fasciculata cells. Postmitochondrial fractions (PMTS) obtained after incubation of adrenal zona glomerulosa with or without AII (10(-7) M) or ACTH (10(-10) M), were able to increase net progesterone synthesis 5-fold in mitochondria isolated from non-stimulated rat zona glomerulosa. In addition, AII in zona glomerulosa produced in vitro steroidogenic fractions that were able to stimulate mitochondria from zona fasciculata cells. Inhibitors of arachidonic acid release and metabolism blocked corticosterone production in fasciculata cells stimulated with ACTH. This concept is supported by the experiment in which bromophenacylbromide and nordihydroguaiaretic acid also blocked the formation of an activated PMTS. In fact, non-activated PMTS, in the presence of exogenous arachidonic acid AA, behaved as an activated PMTS from ACTH stimulated cells. We suggest that the mechanisms of action of ACTH and AII involve an increase in the release of AA and an activation of the enzyme system which converts AA in leukotriene products.