RESUMO
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.
Assuntos
Biomarcadores/sangue , Índice de Massa Corporal , HDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Lipase/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Feminino , Seguimentos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto JovemRESUMO
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.
Assuntos
Transportador 1 de Cassete de Ligação de ATP/genética , HDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Adulto , Biomarcadores/análise , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Feminino , Seguimentos , Estudo de Associação Genômica Ampla , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , PrognósticoRESUMO
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.
Assuntos
Galinhas , Doenças das Aves Domésticas/prevenção & controle , Probióticos , Salmonelose Animal/prevenção & controle , Fagos de Salmonella/fisiologia , Salmonella enteritidis/virologia , Aerossóis , AnimaisRESUMO
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.
Assuntos
Portador Sadio/veterinária , Galinhas/microbiologia , Doenças das Aves Domésticas/prevenção & controle , Salmonelose Animal/prevenção & controle , Fagos de Salmonella/fisiologia , Salmonella/virologia , Animais , Portador Sadio/prevenção & controleRESUMO
OBJECTIVE: To determine the impact of pregnancy on systemic lupus erythematosus (SLE) outcome. METHODS: SLE patients, age >or=16 yrs, disease duration Assuntos
Lúpus Eritematoso Sistêmico
, Complicações na Gravidez
, Transtornos Puerperais/etiologia
, Adulto
, Negro ou Afro-Americano/estatística & dados numéricos
, Métodos Epidemiológicos
, Feminino
, Hispânico ou Latino/estatística & dados numéricos
, Humanos
, Lúpus Eritematoso Sistêmico/etnologia
, Gravidez
, Complicações na Gravidez/etnologia
, Resultado da Gravidez
, Transtornos Puerperais/etnologia
, Porto Rico/epidemiologia
, Índice de Gravidade de Doença
, Fatores Socioeconômicos
, Estados Unidos/epidemiologia
, População Branca/estatística & dados numéricos
RESUMO
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.
Assuntos
Contaminação de Alimentos , Listeria monocytogenes , CarneRESUMO
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.
Assuntos
Ecocardiografia Doppler/métodos , Doenças das Valvas Cardíacas/diagnóstico por imagem , Espondilite Anquilosante/complicações , Disfunção Ventricular Esquerda/diagnóstico por imagem , Adolescente , Adulto , Distribuição por Idade , Idade de Início , Análise de Variância , Valva Aórtica/diagnóstico por imagem , Criança , Pré-Escolar , Intervalos de Confiança , Doenças das Valvas Cardíacas/epidemiologia , Doenças das Valvas Cardíacas/etiologia , Humanos , Incidência , Masculino , Valva Mitral/diagnóstico por imagem , Valores de Referência , Medição de Risco , Sensibilidade e Especificidade , Espondilite Anquilosante/epidemiologia , Disfunção Ventricular Esquerda/epidemiologia , Disfunção Ventricular Esquerda/etiologiaRESUMO
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.
Assuntos
Proteínas de Ligação a DNA , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Proteínas Nucleares , Adulto , Idade de Início , Anticorpos/análise , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Glucoquinase/genética , Glutamato Descarboxilase/imunologia , Fator 1 Nuclear de Hepatócito , Fator 1-alfa Nuclear de Hepatócito , Fator 1-beta Nuclear de Hepatócito , Fator 4 Nuclear de Hepatócito , Humanos , Insulina/metabolismo , Resistência à Insulina , Secreção de Insulina , Lipoproteínas/sangue , Masculino , México , Pessoa de Meia-Idade , Mutação , Linhagem , Fosfoproteínas/genética , Fatores de Transcrição/genéticaRESUMO
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.
Assuntos
Infecções por Astroviridae/epidemiologia , Astroviridae , Indígenas Centro-Americanos , População Rural , Infecções por Adenoviridae/diagnóstico , Infecções por Adenoviridae/imunologia , Astroviridae/genética , Astroviridae/imunologia , Infecções por Astroviridae/imunologia , Infecções por Astroviridae/fisiopatologia , Infecções por Astroviridae/virologia , Infecções por Campylobacter/diagnóstico , Estudos de Coortes , Diarreia Infantil/epidemiologia , Diarreia Infantil/virologia , Disenteria Bacilar/diagnóstico , Fezes/microbiologia , Fezes/virologia , Humanos , Lactente , México/epidemiologia , Prevalência , Estudos Prospectivos , Infecções por Rotavirus/diagnóstico , Infecções por Rotavirus/imunologia , Infecções por Salmonella/diagnóstico , Estações do AnoRESUMO
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.