RESUMEN
During tobacco and e-cigarette use, nicotine is mainly metabolized in the human liver by cytochrome P450 2A6 (CYP2A6). Given that a slower CYP2A6 metabolism has been associated with less vulnerability to develop nicotine dependence, the current studies sought to validate a novel CYP2A6 inhibitor, (5-(4-ethylpyridin-3-yl)thiophen-2-yl)methanamine (DLCI-1), for its effects on intravenous nicotine self-administration. Male and female mice were trained to self-administer nicotine across daily sessions. Once stable responding was achieved, DLCI-1 or vehicle control was administered prior to nicotine sessions. We found that the lower 25 mg/kg and moderate 50 mg/kg doses of DLCI-1 induced a significant decrease in nicotine intake for both males and females. DLCI-1 was further shown to be more effective than a moderate 1 mg/kg dose of bupropion on reducing nicotine intake and did not exert the adverse behavioral effects found with a high 75 mg/kg dose of bupropion. Although mice treated with DLCI-1 self-administered significantly less nicotine, similar nicotine-mediated behavioral effects on locomotion were observed. Together, along with the analysis of nicotine metabolites during self-administration, these findings support the contention that blocking hepatic nicotine metabolism would allow for similar activation of nicotinic acetylcholine receptors at lower nicotine doses. Moreover, these effects of DLCI-1 were specific to nicotine self-administration, as DLCI-1 did not result in any behavioral changes during food self-administration. Taken together, these studies validate DLCI-1 as a novel compound to decrease nicotine consumption, which may thereby promote tobacco and nicotine product cessation. SIGNIFICANCE STATEMENT: Current pharmacological approaches for nicotine and tobacco cessation have only been able to achieve limited efficaciousness in promoting long-term abstinence. In this work, we characterize the effects of a novel compound, (5-(4-ethylpyridin-3-yl)thiophen-2-yl)methanamine (DLCI-1), which inhibits the main enzyme that metabolizes nicotine, and we report a significant decrease in intravenous nicotine self-administration in male and female mice, supporting the potential of DLCI-1 as a novel tobacco cessation pharmacotherapeutic.
Asunto(s)
Citocromo P-450 CYP2A6/antagonistas & inhibidores , Inhibidores Enzimáticos/uso terapéutico , Agentes para el Cese del Hábito de Fumar/uso terapéutico , Tiofenos/uso terapéutico , Tabaquismo/tratamiento farmacológico , Animales , Citocromo P-450 CYP2A6/metabolismo , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/efectos adversos , Inhibidores Enzimáticos/farmacología , Femenino , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Nicotina/metabolismo , Agentes para el Cese del Hábito de Fumar/administración & dosificación , Agentes para el Cese del Hábito de Fumar/efectos adversos , Agentes para el Cese del Hábito de Fumar/farmacología , Tiofenos/administración & dosificación , Tiofenos/efectos adversos , Tiofenos/farmacologíaRESUMEN
The rivers originating in the southern Andes (18°-55°S) support numerous ecosystems and a large number of human populations and socio-economic activities in the adjacent lowlands of Chile, Argentina and Bolivia. Here we show that ca. 75% of the total variance in the streamflow records from this extensive region can be explained by only eight spatially coherent patterns of variability. Five (three) of these Andean patterns exhibit extreme dry (wet) conditions in recent years, with strong interannual variations in northern Chile; long-term drying trends between 31° and 41°S; a transitional pattern in the central Patagonian Andes; and increasing trends in northwestern Argentina and southern Bolivia, the Fueguian Andes, and the eastern portion of the South Patagonian Icefield. Multivariate regression analyses show that large-scale indices of ENSO variability can predict 20% to 45% of annual runoff variability between 28° and 46°S. The influence of Antarctic and North Pacific indices becomes more relevant south of 43°S and in northwestern Argentina and southern Bolivia, respectively, but their overall skill as predictors of Andean streamflows is weak. The analyses provide relevant new information to improve understanding of the spatial coherence, the main temporal features, and the ocean-atmospheric forcings of surface runoff across the southern Andes.
RESUMEN
The influx of immigrants has increased diversity among ethnic minorities and indicates that they may take multiple integration paths in American society. Previous research on ethnic integration has often focused on panethnic differences, and few have explored ethnic diversity within a racial or panethnic context. Using 2000 U.S. census data for Puerto Rican-, Mexican-, Chinese-, and Filipino-origin individuals, we examine differences in marriage and cohabitation with whites, with other minorities, within a panethnic group, and within an ethnic group by nativity status. Ethnic endogamy is strong and, to a lesser extent, so is panethnic endogamy. Yet, marital or cohabiting unions with whites remain an important path of integration but differ significantly by ethnicity, nativity, age at arrival, and educational attainment. Meanwhile, ethnic differences in marriage and cohabitation with other racial or ethnic minorities are strong. Our analysis supports that unions with whites remain a major path of integration, but other paths of integration also become viable options for all ethnic groups.
Asunto(s)
Asiático/etnología , Diversidad Cultural , Emigrantes e Inmigrantes/estadística & datos numéricos , Hispánicos o Latinos/etnología , Matrimonio/tendencias , Población Blanca/estadística & datos numéricos , Aculturación , Adulto , Asiático/estadística & datos numéricos , Censos , China/etnología , Escolaridad , Femenino , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Masculino , México/etnología , Grupos Minoritarios/estadística & datos numéricos , Filipinas/etnología , Puerto Rico/etnología , Estados Unidos , Población Blanca/etnología , Adulto JovenRESUMEN
Of 17 infants requiring hospitalization for primary soy or cow milk protein intolerance, six infants (35%) had transient methemoglobinemia. Reexposure to the offending protein caused diarrhea, metabolic acidosis, and transient methemoglobinemia in all patients. These six patients represented 65% of the total hospitalizations resulting from methemoglobinemia of any cause.
Asunto(s)
Diarrea Infantil/etiología , Proteínas en la Dieta/efectos adversos , Glycine max/efectos adversos , Alimentos Infantiles/efectos adversos , Metahemoglobinemia/etiología , Proteínas de la Leche/efectos adversos , Proteínas de Vegetales Comestibles/efectos adversos , Acidosis/etiología , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Proteínas de SojaRESUMEN
Enteropathogenic Escherichia coli (0111:K58:H-) was isolated from the small bowel of two infants with chronic diarrhea. Small bowel biopsy revealed focal adherence of the bacteria to the epithelium, accompanied by inflammation of the tissue. The isolates also adhered to tissue culture cells in densely packed aggregates. The pattern of adherence to tissue culture cells were found only among strains of serogroups 0111 and 0119 when 196 enteric E. coli isolates were tested. The pathogenic mechanism of enteropathogenic E. coli thus appears related to dense colonization of intestinal tissue. Adherent strains may be detected by tissue culture assay.
Asunto(s)
Diarrea/microbiología , Infecciones por Escherichia coli/patología , Biopsia , Enfermedad Crónica , Técnicas de Cultivo , Diarrea/patología , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Lactante , Intestino Delgado/microbiología , Intestino Delgado/patología , MasculinoAsunto(s)
Sistema Nervioso Autónomo , Diarrea/etiología , Motilidad Gastrointestinal , Enfermedades del Sistema Nervioso/complicaciones , Preescolar , Unión Esofagogástrica/fisiopatología , Esófago/fisiopatología , Femenino , Ácido Homovanílico/orina , Humanos , Enfermedades del Sistema Nervioso/fisiopatología , Enfermedades del Sistema Nervioso/orina , Norepinefrina/orina , Presión , Ácido Vanilmandélico/orinaRESUMEN
Fifteen patients with recurrent acute respiratory symptoms were evaluated for gastroesophageal reflux. All 15 had barium esophagrams. Ten of 15 had acid reflux tests performed and lower esophageal sphincter pressures measured. The data were compared to those in 23 patients with no acid reflux and 23 patients with positive acid reflux but no respiratory symptoms. Ten of ten patients with respiratory symptoms who were evaluated by the acid reflux test had positive results. The remaining five demonstrated GER by barium esophagram. LES pressure measurements in the ten patients were 11.3 +/- 1.5 mm Hg, which was significantly lower than the pressures in the acid reflux-negative group (20.3 +/- 1.3 mm Hg, P less than 0.001) but not different than in the patients with GER but no respiratory symptoms (13.9 +/- 1.5 mm Hg, P greater than 0.05). GER secondary to an incompetent lower esophageal sphincter may be one cause of recurrent acute respiratory disease in infants and children.
Asunto(s)
Unión Esofagogástrica/fisiopatología , Reflujo Gastroesofágico/complicaciones , Enfermedades Pulmonares/etiología , Enfermedad Aguda , Adolescente , Sulfato de Bario , Niño , Preescolar , Unión Esofagogástrica/patología , Esófago/diagnóstico por imagen , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/terapia , Humanos , Lactante , Enfermedades Pulmonares/patología , Enfermedades Pulmonares/fisiopatología , Presión , Radiografía , RecurrenciaRESUMEN
The one-hour blood xylose concentration was evaluated to determine its usefulness as a screening test for small bowel mucosal disease in infants and children. Six of 13 patients with one-hour blood xylose levels of less than 20 mg/dl had normal small bowel biopsies by light microscopy. Five of 20 children with normal one-hour xylose levels had abnormal small bowel villous architecture. Because of the significant false positive (46%) and false negative results (25%), the one-hour blood xylose concentration should not be used as the sole indicator for small bowel biopsy in infants and children with chronic diarrhea.
Asunto(s)
Intestino Delgado , Xilosa , Biopsia , Carotenoides/sangre , Niño , Preescolar , Femenino , Humanos , Lactante , Enfermedades Intestinales/sangre , Enfermedades Intestinales/diagnóstico , Enfermedades Intestinales/patología , Mucosa Intestinal/patología , Intestino Delgado/patología , Factores de Tiempo , Xilosa/sangreRESUMEN
Two infants with short bowel syndrome were successfully weaned from total parenteral alimentation by means of a continuous intragastric infusion through a gastrostomy of a dilute elemental diet. Each patient had received TPA for 9 and 3 months, respectively, and had failed to thrive while receiving other therapeutic formulas. Gradual transition to bolus feeling was accomplished in each infant after 2 1/2 and 2 months, respectively. Our results demonstrate that a continuous infusion of a dilute elemental diet in large volumes can provide adequate calories for growth and maintain positive fluid and electrolyte balance.