RESUMO
Undernutrition represents a major public health challenge for middle- and low-income countries. This study aimed to evaluate whether a multideficient Northeast Brazil regional basic diet (RBD) induces acute morphological and functional changes in the ileum of mice. Swiss mice (â¼25 g) were allocated into two groups: i) control mice were fed a standard diet and II) undernourished mice were fed the RBD. After 7 days, mice were killed and the ileum collected for evaluation of electrophysiological parameters (Ussing chambers), transcription (RT-qPCR) and protein expression (western blotting) of intestinal transporters and tight junctions. Body weight gain was significantly decreased in the undernourished group, which also showed decreased crypt depth but no alterations in villus height. Electrophysiology measurements showed a reduced basal short circuit current (Isc) in the undernourished group, with no differences in transepithelial resistance. Specific substrate-evoked Isc related to affinity and efficacy (glutamine and alanyl-glutamine) were not different between groups, except for the maximum Isc (efficacy) induced by glucose. Transcription of Sglt1 and Pept1 was significantly higher in the undernourished group, while SN-2 transcription was decreased. No changes were found in transcription of CAT-1 and CFTR, while claudin-2 and occludin transcriptions were significantly increased in the undernourished group. Despite mRNA changes, SGLT-1, PEPT-1, claudin-2 and occludin protein expression showed no difference between groups. These results demonstrate early effects of the RBD on mice, which include reduced body weight and crypt depth in the absence of significant alterations to villus morphology, intestinal transporters and tight junction expression.
Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Crescimento/fisiologia , Íleo/anatomia & histologia , Íleo/metabolismo , Desnutrição/metabolismo , Desnutrição/fisiopatologia , Doença Aguda , Animais , Peso Corporal , Modelos Animais de Doenças , Ingestão de Energia/fisiologia , Immunoblotting , Absorção Intestinal/fisiologia , Transporte de Íons/fisiologia , Masculino , Desnutrição/complicações , Proteínas de Membrana Transportadoras/análise , Camundongos , RNA Mensageiro , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas de Junções Íntimas/análise , Proteínas de Junções Íntimas/metabolismo , Fatores de TempoRESUMO
Undernutrition represents a major public health challenge for middle- and low-income countries. This study aimed to evaluate whether a multideficient Northeast Brazil regional basic diet (RBD) induces acute morphological and functional changes in the ileum of mice. Swiss mice (∼25 g) were allocated into two groups: i) control mice were fed a standard diet and II) undernourished mice were fed the RBD. After 7 days, mice were killed and the ileum collected for evaluation of electrophysiological parameters (Ussing chambers), transcription (RT-qPCR) and protein expression (western blotting) of intestinal transporters and tight junctions. Body weight gain was significantly decreased in the undernourished group, which also showed decreased crypt depth but no alterations in villus height. Electrophysiology measurements showed a reduced basal short circuit current (Isc) in the undernourished group, with no differences in transepithelial resistance. Specific substrate-evoked Isc related to affinity and efficacy (glutamine and alanyl-glutamine) were not different between groups, except for the maximum Isc (efficacy) induced by glucose. Transcription of Sglt1 and Pept1 was significantly higher in the undernourished group, while SN-2 transcription was decreased. No changes were found in transcription of CAT-1 and CFTR, while claudin-2 and occludin transcriptions were significantly increased in the undernourished group. Despite mRNA changes, SGLT-1, PEPT-1, claudin-2 and occludin protein expression showed no difference between groups. These results demonstrate early effects of the RBD on mice, which include reduced body weight and crypt depth in the absence of significant alterations to villus morphology, intestinal transporters and tight junction expression.
Assuntos
Animais , Masculino , Coelhos , Desnutrição/fisiopatologia , Desnutrição/metabolismo , Crescimento/fisiologia , Íleo/anatomia & histologia , Íleo/metabolismo , Fenômenos Fisiológicos da Nutrição Animal , Fatores de Tempo , Peso Corporal , Ingestão de Energia/fisiologia , RNA Mensageiro , Immunoblotting , Doença Aguda , Transporte de Íons/fisiologia , Desnutrição/complicações , Modelos Animais de Doenças , Absorção Intestinal/fisiologiaRESUMO
OBJECTIVE: To evaluate the epidemiology of Giardia lamblia infection, investigate factors which might be associated with clinical manifestations and recurrence, and examine the role of copathogens in disease course. METHODS: Prospective 4-year cohort study of children born in an urban slum in north-eastern Brazil. RESULTS: Of 157 children followed for > or = 3 months, 43 (27.4%) were infected with Giardia. The organism was identified in 8.8% of all stool specimens, and although found with similar frequency in non-diarrhoeal (7.4%) and diarrhoeal stools (9.7%), was more common in children with persistent (20.6%) than acute diarrhoea (7.6%, P=0.002). Recurrent or relapsing infections were common (46%). Children with symptomatic infections had significantly lower weight-for-age and height-for-age than asymptomatic children. Copathogens were not associated with disease course. CONCLUSION With its protean clinical manifestations, Giardia may be associated with substantial morbidity amongst children in Brazil.
Assuntos
Giardia lamblia/isolamento & purificação , Giardíase/epidemiologia , Animais , Brasil/epidemiologia , Diarreia/epidemiologia , Diarreia/parasitologia , Fezes/parasitologia , Humanos , Lactente , Estudos Longitudinais , Pobreza , População UrbanaRESUMO
BACKGROUND: Although the acute mortality from diarrhoeal diseases is well recognized, the potentially prolonged impact of early childhood diarrhoea on background growth and development is often overlooked. To examine the magnitude and duration of the association of early childhood enteric infections with growth faltering in later childhood, we investigated associations of early childhood diarrhoea (0-2 years) and intestinal helminthiases with nutritional status from age 2 to 7 years. METHODS: Twice-weekly diarrhoea surveillance and quarterly anthropometrics were followed from 1989 to 1998 in 119 children born into a Northeast Brazilian shantytown. RESULTS: Diarrhoea burdens at 0-2 years old were significantly associated with growth faltering at ages 2-7 years, even after controlling for nutritional status in infancy, helminthiases at 0-2 years old, family income, and maternal education by Pearson correlation, multivariate linear regression, and repeat measures analysis. The average 9.1 diarrhoeal episodes before age 2 years was associated with a 3.6 cm (95% CI : 0.6-6.6 cm) growth shortfall at age 7 years. Early childhood helminthiasis was also associated with linear growth faltering and a further 4.6 cm shortfall (95% CI : 0.8-7.9 cm) at age 7 years. CONCLUSIONS: Early childhood diarrhoea and helminthiases independently associate with substantial linear growth shortfalls that continue beyond age 6 years. Targeted interventions for their control may have profound and lasting growth benefits for children in similar settings.
Assuntos
Diarreia Infantil/fisiopatologia , Transtornos do Crescimento/fisiopatologia , Helmintíase/fisiopatologia , Antropometria , Brasil/epidemiologia , Criança , Pré-Escolar , Diarreia Infantil/epidemiologia , Feminino , Transtornos do Crescimento/epidemiologia , Helmintíase/epidemiologia , Humanos , Lactente , Recém-Nascido , Modelos Lineares , Masculino , Estado Nutricional , Vigilância da População , Pobreza , Estudos Prospectivos , Fatores de RiscoRESUMO
Vitamin A (retinol) is required to maintain immunity and epithelial turnover and is a key micronutrient needed for combating infection. Vitamin A actions on the immune system are diverse and cannot be accounted for by a single effect or mechanism. The actions of retinol in maintaining gut integrity in humans and immunoglobulin levels in mice was investigated. For 30 children, performance on the lactulose/mannitol test, a test commonly used to assess intestinal barrier function, was inversely correlated (P=.012) with serum retinol concentrations. Thus, children with lower serum retinol, and presumably poorer vitamin A nutritional status, are more likely to have impaired intestinal integrity. Knockout mice that have impairments in plasma retinol transport have circulating immunoglobulin levels that are half those observed in matched wild type mice. No differences were observed in B and T cell populations present in spleen, thymus, and bone marrow.
Assuntos
Absorção Intestinal , Mucosa Intestinal/fisiologia , Proteínas de Ligação ao Retinol/metabolismo , Vitamina A/fisiologia , Animais , Brasil , Estudos de Coortes , Humanos , Recém-Nascido , Lactulose/farmacocinética , Estudos Longitudinais , Manitol/farmacocinética , Camundongos , Camundongos Knockout , Estado Nutricional , Análise de Regressão , Proteínas Plasmáticas de Ligação ao Retinol , Vitamina A/sangue , Vitamina A/farmacologiaRESUMO
Persistent diarrhea (PD; duration >/=14 days) is a growing part of the global burden of diarrheal diseases. A 45-month prospective cohort study (with illness, nutritional, and microbiologic surveillance) was conducted in a shantytown in northeastern Brazil, to elucidate the epidemiology, nutritional impact, and causes of PD in early childhood (0-3 years of age). A nested case-control design was used to examine children's diarrhea burden and nutritional status before and after a first PD illness. PD illnesses accounted for 8% of episodes and 34% of days of diarrhea. First PD illnesses were preceded by a doubling of acute diarrhea burdens, were followed by further 2.6-3.5-fold increased diarrhea burdens for 18 months, and were associated with acute weight shortfalls. Exclusively breast-fed children had 8-fold lower diarrhea rates than did weaned children. PD-associated etiologic agents included Cryptosporidium, Giardia, enteric adenoviruses, and enterotoxigenic Escherichia coli. PD signals growth shortfalls and increased diarrhea burdens; children with PD merit extended support, and the illness warrants further study to elucidate its prevention, treatment, and impact.
Assuntos
Diarreia/epidemiologia , Estado Nutricional , Infecções Bacterianas/epidemiologia , Brasil/epidemiologia , Aleitamento Materno , Estudos de Coortes , Diarreia/microbiologia , Diarreia/parasitologia , Feminino , Humanos , Incidência , Recém-Nascido , Estudos Longitudinais , Doenças Parasitárias/epidemiologia , Pobreza , Prevalência , Estudos Prospectivos , Fatores de Risco , Fatores Socioeconômicos , Viroses/epidemiologiaRESUMO
BACKGROUND: Endemic diarrhea and its associated malnutrition remain leading causes of childhood morbidity and mortality in developing countries. This study was undertaken to describe changes in the incidence of diarrhea and prevalence of malnutrition among children in an urban Brazilian shantytown from 1989 to 1996. A secondary purpose was to examine associations between malnutrition and increased incidence and duration of diarrhea. METHODS: From August 1989 through December 1996 a dynamic birth cohort of 315 children was followed for surveillance of diarrhea and nutrition. Study homes were visited twice or thrice weekly to assess the occurrence of diarrhea. Length and weight of the subjects were measured quarterly. Poisson regression was used to test for associations between prior nutritional status and subsequent diarrhea during a quarter. Multiple regression was used to test for an association between nutritional status and episode duration. RESULTS: Declines in both age-adjusted attack rates (6.0 episodes/child-year in study year 3 [1991] to 2.5 episodes per child-year in study year 8 [1996] and days of diarrhea per child-year (30.8 days/child-year in year 3 to 8.5 days/child-year in year 8) were correlated with yearly improvements in mean nutritional status (R2= 0.84, P < 0.05, for mean length-for-age with mean number of episodes/child-year [corrected]. Both length- and weight-for-age were significant predictors of diarrhea incidence, including persistent episodes (> or =14 d), but not duration. CONCLUSIONS: These results demonstrate marked changes over time in the diarrhea burden and nutritional status of children in this population and provide further evidence of a significant association between malnutrition and increased incidence of diarrhea.
Assuntos
Diarreia/epidemiologia , Distúrbios Nutricionais/epidemiologia , Pobreza , População Urbana , Brasil/epidemiologia , Pré-Escolar , Humanos , Incidência , Lactente , Recém-Nascido , Estudos Longitudinais , Estado Nutricional , Vigilância da População , PrevalênciaRESUMO
To determine potential, long-term deficits associated with early childhood diarrhea and parasitic infections, we studied the physical fitness (by the Harvard Step Test) and cognitive function (by standardized tests noted below) of 26 children who had complete surveillance for diarrhea in their first 2 years of life and who had continued surveillance until 6-9 years of age in a poor urban community (favela) in Fortaleza in northeast Brazil. Early childhood diarrhea at 0-2 years of age correlated with reduced fitness by the Harvard Step Test at 6-9 years of age (P = 0.03) even after controlling for anthropometric and muscle area effects, anemia, intestinal helminths, Giardia infections, respiratory illnesses, and socioeconomic variables. Early childhood cryptosporidial infections (6 with diarrhea and 3 without diarrhea) were also associated with reduced fitness at 6-9 year of age, even when controlling for current nutritional status. Early diarrhea did not correlate with activity scores (P = 0.697), and early diarrhea remained significantly correlated with fitness scores (P = 0.035) after controlling for activity scores. Early diarrhea burdens also correlated in pilot studies with impaired cognitive function using a McCarthy Draw-A-Design (P = 0.01; P = 0.017 when controlling for early helminth infections), Wechsler Intelligence Scale for Children coding tasks (P = 0.031), and backward digit span tests (P = 0.045). These findings document for the first time a potentially substantial impact of early childhood diarrhea and cryptosporidial infections on subsequent functional status. If confirmed, these findings have major implications for calculations of global disability adjusted life years and for the importance and potential cost effectiveness of targeted interventions for early childhood diarrhea.
Assuntos
Desenvolvimento Infantil , Transtornos Cognitivos/etiologia , Criptosporidiose/complicações , Diarreia Infantil/complicações , Aptidão Física/fisiologia , Animais , Brasil , Criança , Pré-Escolar , Transtornos Cognitivos/parasitologia , Estudos de Coortes , Criptosporidiose/fisiopatologia , Criptosporidiose/psicologia , Cryptosporidium , Diarreia Infantil/fisiopatologia , Diarreia Infantil/psicologia , Fezes/parasitologia , Feminino , Seguimentos , Hematócrito , Humanos , Lactente , Recém-Nascido , Masculino , Projetos Piloto , Pobreza , Estudos Prospectivos , Estatísticas não Paramétricas , População UrbanaRESUMO
A prospective, 4-year cohort study of children born in an urban slum in northeastern Brazil was undertaken to elucidate the epidemiology of Cryptosporidium infection in an endemic setting, describe factors associated with Cryptosporidium-associated persistent diarrhea, and clarify the importance of copathogens in symptomatic cryptosporidiosis. A total of 1476 episodes of diarrhea, accounting for 7581 days of illness (5.25 episodes/child-year), were recorded: of these, 102 episodes (6.9%) were persistent. Cryptosporidium oocysts were identified in 7.4% of all stools, and they were found more frequently in children with persistent diarrhea (16.5%) than in those with acute (8.4%) or no (4.0%) diarrhea (P<.001). Low-birth-weight children and those living in densely crowded subdivisions were at greater risk for symptomatic infection. Disease course was highly variable and was not associated with the presence of copathogens. Recurrent Cryptosporidium infection and relapsing diarrhea associated with it were moderately common. In light of these data, the applicability of the current World Health Organization diarrheal definitions to Cryptosporidium-associated diarrheal episodes may need to be reconsidered.