ABSTRACT
Besides its role as a carboxylase cofactor, biotin has a wide repertoire of effects on gene expression, development and metabolism. Pharmacological concentrations of biotin enhance insulin secretion and the expression of genes and signaling pathways that favor islet function in vitro. However, the in vivo effects of biotin supplementation on pancreatic islet function are largely unknown. In the present study, we investigated whether in vivo biotin supplementation in the diet has positive effects in rodent pancreatic islets. Male BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet over 8 weeks postweaning and tested for glucose homeostasis, insulin secretion, islet gene expression and pancreatic morphometry. Insulin secretion increased from the islets of biotin-supplemented mice, together with the messenger RNA (mRNA) expression of several transcription factors regulating insulin expression and secretion, including forkhead box A2, pancreatic and duodenal homeobox 1 and hepatocyte nuclear factor 4α. The mRNA abundance of glucokinase, Cacna1d, acetyl-CoA carboxylase, and insulin also increased. Consistent with these effects, glucose tolerance improved, and glucose-stimulated serum insulin levels increased in biotin-supplemented mice, without changes in fasting glucose levels or insulin tolerance. Biotin supplementation augmented the proportion of beta cells by enlarging islet size and, unexpectedly, also increased the percentage of islets with alpha cells at the islet core. mRNA expression of neural cell adhesion molecule 1, an adhesion protein participating in the maintenance of islet architecture, decreased in biotin-supplemented islets. These findings provide, for the first time, insight into how biotin supplementation exerts its effects on function and proportion of beta cells, suggesting a role for biotin in the prevention and treatment of diabetes.
Subject(s)
Biotin/pharmacology , Glucose/metabolism , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/metabolism , Insulin/metabolism , Animals , Biotin/blood , Body Weight/drug effects , Dietary Supplements , Eating/drug effects , Gene Expression Regulation/drug effects , Glucokinase/genetics , Homeostasis/drug effects , Insulin Secretion , Islets of Langerhans/cytology , Islets of Langerhans/drug effects , Islets of Langerhans/metabolism , Male , Mice , Mice, Inbred BALB C , Pyruvate Carboxylase/genetics , Pyruvate Carboxylase/metabolismABSTRACT
Blindness is a pervasive sensory condition that imposes diverse difficulties to carry on with activities of daily living. In blind individuals, the brain is subjected to a large scale reorganization characterized by expanded cortical territories associated with somatosensory and auditory functions and the recruitment of the former visual areas to perform bimodal somatosensory and auditory integration. This poses obstacles to efforts aimed at reassigning visual functions to the recruited visual cortex in the blind, especially after the end of the ontogentic sensitive period. Devising pharmacological measures to modulate the magnitude of brain plasticity could improve our chances of recovering visual functions in the blind. Here, by using the primary somatosensory cortex (S1) in the rat as a working model, we showed that valproic acid administered through the mother's milk prevents cortical reorganization in blinded rats by delaying neuronal histone de-acetylation. These results suggest that in the future, we might be able to devise epigenetic pharmacological measures that could improve our chances of reassigning visual functions to the once deprived former visual cortex in the blind, by modulating the magnitude of brain plasticity during critical times of development.
Subject(s)
Blindness/drug therapy , Chromatin Assembly and Disassembly/drug effects , Epigenomics , Neuronal Plasticity/drug effects , Somatosensory Cortex/drug effects , Valproic Acid/pharmacology , Animals , Humans , Rats , Rats, Wistar , Somatosensory Cortex/physiologyABSTRACT
OBJECTIVE: To develop a valid, reliable, and sensitive self-administered questionnaire in Spanish to measure the knowledge asthmatic patients have of their disease. PATIENTS AND METHODS: The face and content validity of the questions was established by consensus among expert pulmonologists. To determine the importance of the questions, they were put to 100 participating asthmatic patients. The number of questions was reduced by consensus taking into account the importance given to each question by these patients. A further 25 patients participated in the assessment of reliability and sensitivity. The questionnaire was administered 5 times: twice before and 3 times after an educational intervention. The direct and indirect external consistency (kappa statistic) and the overall kappa value were determined. Sensitivity was assessed from the number of correct answers before and after the intervention (Wilcoxon test; P< .05) and from the percentage change (>40% was clinically significant). RESULTS: Fifty-nine questions were drawn up and the final version included 20. The test-retest consistency was between 0.81 and 1 in 76% of the cases before the intervention and in 92% after it. The kappa statistic before the intervention was between 0.41 and 1 in 96% of the cases, and between 0.81 and 1 in 88% afterwards. The overall kappa values before and after the intervention were 0.12 and 0.43, respectively. The median sensitivity, measured as percentage change, was 67% and 10 patients showed an improvement between 81% and 233%. CONCLUSIONS: The questionnaire is reliable, has face and content validity, and is very sensitive to change. In view of these results, this instrument is useful for measuring the knowledge that asthmatic patients have of their disease in clinical practice and investigation.
Subject(s)
Asthma , Health Knowledge, Attitudes, Practice , Surveys and Questionnaires , Adolescent , Adult , Aged , Child , Humans , Middle AgedABSTRACT
Objetivo: Desarrollar un cuestionario en español, autoadministrado, que mida los conocimientos del paciente asmático en relación con su enfermedad y que sea válido, fiable y sensible. Pacientes y métodos: La validez de apariencia y contenido de las preguntas redactadas se estableció por consenso de neumólogos expertos. Para la calificación de la importancia de las preguntas participaron 100 pacientes asmáticos. La reducción del número de preguntas para la versión final del cuestionario se realizó por consenso y tomando en consideración la escala de importancia determinada por los mismos pacientes. Para evaluar la fiabilidad y sensibilidad participaron otros 25 pacientes. El cuestionario se aplicó en 5 ocasiones diferentes: 2 previas y 3 posteriores a la intervención educativa. Se midió la consistencia externa directa e indirecta (índice kappa) y la kappa global. La sensibilidad se determinó con el número de aciertos antes y después de la intervención (prueba de Wilcoxon; p 40%, clínicamente significativo). Resultados: Se redactaron 59 preguntas y la versión final del cuestionario consta de 20. La consistencia directa antes y después de la intervención fue de 0,81-1 en el 76 y el 92% de los casos, respectivamente. El índice kappa antes de la intervención se situó entre 0,41 y 1 en el 96% de los casos, y después fue de 0,81-1 en el 88%. La kappa global antes y después de la intervención fue de 0,12 y 0,43, respectivamente. La mediana de la sensibilidad, medida en porcentaje de cambio, fue del 67% y 10 pacientes mostraron una mejora entre el 81 y el 233%. Conclusiones: El cuestionario es fiable, reúne los criterios de validez de contenido y apariencia y es muy sensible al cambio. En virtud de la magnitud de los resultados, es un instrumento útil para medir los conocimientos del paciente asmático en la práctica clínica o la investigación
Objective: To develop a valid, reliable, and sensitive self-administered questionnaire in Spanish to measure the knowledge asthmatic patients have of their disease. Patients and methods: The face and content validity of the questions was established by consensus among expert pulmonologists. To determine the importance of the questions, they were put to 100 participating asthmatic patients. The number of questions was reduced by consensus taking into account the importance given to each question by these patients. A further 25 patients participated in the assessment of reliability and sensitivity. The questionnaire was administered 5 times: twice before and 3 times after an educational intervention. The direct and indirect external consistency (k statistic) and the overall k value were determined. Sensitivity was assessed from the number of correct answers before and after the intervention (Wilcoxon test; P40% was clinically significant). Results: Fifty-nine questions were drawn up and the final version included 20. The test-retest consistency was between 0.81 and 1 in 76% of the cases before the intervention and in 92% after it. The k statistic before the intervention was between 0.41 and 1 in 96% of the cases, and between 0.81 and 1 in 88% afterwards. The overall k values before and after the intervention were 0.12 and 0.43, respectively. The median sensitivity, measured as percentage change, was 67% and 10 patients showed an improveme between 81% and 233%. Conclusions: The questionnaire is reliable, has face and content validity, and is very sensitive to change. In view of these results, this instrument is useful for measuring the knowledge that asthmatic patients have of their disease in clinical practice and investigation
Subject(s)
Male , Female , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Aged , Humans , Health Knowledge, Attitudes, Practice , Asthma , Reproducibility of Results , Sensitivity and Specificity , Mexico , Severity of Illness IndexABSTRACT
OBJECTIVE: To describe the tuberculosis morbidity and mortality trends in Mexico, by comparing the data reported by the Ministry of Health (MH) and the World Health Organization (WHO) between 1981 and 1998. MATERIAL AND METHODS: The number of cases notified in the past few years, their rates, and the trends of the disease in Mexico were analyzed. The incidence of smear-positive pulmonary tuberculosis was estimated for 1997 and 1998 with the annual tuberculosis infection risk (ATIR), to estimate the percentage of bacilliferous cases in 1997-1998. RESULTS: WHO reported more tuberculosis cases for Mexico than the MH. However, this difference has decreased throughout the years. The notification of smear-positive cases remained stable during 1993-1998. The estimated percentages of detection were 66% for 1997 and 26% for 1998 (based on ATIR of 0.5%). Tuberculosis mortality decreased gradually (6.7% per year) between 1990 and 1998, whereas the number of new cases increased, suggesting the persistence of disease transmission in the population. CONCLUSIONS: Inconsistencies between case notifications from national data and WHO were considerable, but decreased progressively during the study period. According to ATIR estimations, a considerable number of infectious tuberculosis cases are not detected. The English version of this paper is available at: http://www.insp.mx/salud/index.html.
Subject(s)
Government Agencies/statistics & numerical data , Registries , Tuberculosis, Pulmonary/mortality , World Health Organization , Adolescent , Adult , Aged , Child , Child, Preschool , Disease Notification , Humans , Incidence , Infant , Mexico/epidemiology , Middle AgedABSTRACT
Biotin deficiency is known to affect immune function in both humans and experimental animals. In this study, we determined the effect of biotin deficiency on 4-wk-old Balb/cAnN mice during 20 wk of experimentation. The growth rate of mice slowed significantly during the first 6 wk of consumption of a diet designed to induce biotin deficiency; thereafter, from weeks 7 to 20 there was progressive weight loss in the mice receiving the biotin-deficient diet. In the livers of biotin-deficient mice, the specific activities of two biotin-dependent enzymes--pyruvate carboxylase and propionyl-CoA carboxylase--decreased by as much as 75% and 80%, respectively, and in spleen lymphocytes the specific activities of these two enzymes decreased by 63% and 75%, respectively. With respect to the effects of biotin deficiency on the immune system, we observed statistically significant changes in both the absolute number of spleen cells and in the proportions of spleen cells carrying different phenotypic markers: after 16 wk the percentage of cells expressing surface immunoglobulin (sIg) decreased from 47% (control and supplemented) to 27% (deficient) and CD3+ cells increased from 42% (control and supplemented) to 54% (deficient). The mitogen-induced proliferation of spleen cells from deficient mice was lower than that of spleen cells from the control mice. These findings suggest that biotin could have an important role in lymphocyte maturation and responsiveness to stimulation, and consequently in the capacity of the immune system to respond to an antigenic challenge.
Subject(s)
Biotin/deficiency , Lymphocytes/immunology , Spleen/pathology , Animals , Biotin/blood , Body Weight , Carboxy-Lyases/metabolism , Cell Division/drug effects , Concanavalin A/pharmacology , Deficiency Diseases/enzymology , Deficiency Diseases/immunology , Deficiency Diseases/pathology , Lymphocyte Subsets , Lymphocytes/drug effects , Male , Methylmalonyl-CoA Decarboxylase , Mice , Mice, Inbred BALB C , Pyruvate Carboxylase/metabolism , Spleen/drug effects , Spleen/immunologyABSTRACT
Intraventricular administration of cerebrospinal fluid (CSF) obtained from sleep deprived (SD) animals and vasoactive intestinal peptide (VIP) have been shown to increase rapid eye movement (REM) sleep. It has thus been suggested that VIP may accumulate in the CSF as a consequence of waking, and might thus be partly responsible for the subsequent rebound of REM sleep which follows prolonged wakefulness. To this data there are no studies testing this hypothesis. The purpose of this study, therefore, was to determine REM rebound following the extraction of CSF immediately after REMSD and to quantify by radioimmunoassay (RIA) the concentration of VIP in the CSF of progressively increasing REMSD periods. The results showed that REM rebound normally seen following REMSD is reduced by extraction of CSF, and that VIP concentration in such CSF is augmented. The results are discussed in terms of the possibility that waking induces an accumulation of VIP in the CSF, which is in turn involved in the production of REM sleep.
