Supplementation with sodium butyrate protects against antibiotic-induced increases in ethanol consumption behavior in mice.

BACKGROUND: We have recently reported that oral treatment of adult male C57BL/6J mice with a non-absorbable antibiotic cocktail resulted in an increase in ethanol intake and in significant reductions in butyrate-producing gut microbiota populations. This work led us to hypothesize that reduction in butyrate levels within the gut is linked to antibiotic-induced increases in voluntary ethanol consumption. OBJECTIVE: This study tested whether ad libitum sodium butyrate supplementation can prevent antibiotic-induced ethanol consumption in mice. METHODS: Sodium butyrate was provided to adult male C57BL/6J mice in drinking water alone or in combination with antibiotic cocktail. Effects on ethanol (20%) intake were measured using drinking in the dark and modified 2-bottle choice paradigms. Body parameters, food and liquid intake, cecum, and adipose tissues were measured during and/or at the conclusion of the drinking in the dark study. Cecal 16s rRNA was analyzed for microbiota diversity and changes in specific bacterial phyla/species. RESULTS: In drinking in the dark, sodium butyrate supplementation prevented antibiotic-induced increases in ethanol intake without altering basal ethanol consumption. Furthermore, sodium butyrate supplementation lowered ethanol preference in the 2-bottle choice study. Ethanol intake was correlated to specific bacterial phyla/species. Sodium butyrate did not affect the changes in microbiota diversity and composition induced by antibiotic cocktail. CONCLUSIONS: The findings support a role of gut microbiota-derived butyrate in regulating alcohol-induced behaviors. Additionally, the work contributes to efforts in development of novel microbiome-based strategies as novel preventative and intervention-based therapeutics to address alcohol use disorder.

[Zinc and epilepsy: is there a causal relation between them?]. / Zinc y epilepsia: existe una relación causal?

INTRODUCTION: Zinc is a fundamental trace element for an adequate nervous system function. It has been suggested that in the brain, a zinc homeostasis alteration may be associated with the genesis of epilepsy, although it is not yet determined if concentrations of zinc are a cause or a consequence of seizures. Another poorly studied aspect is the relationship between antiepileptic drugs and the neuronal zinc behaviour. DEVELOPMENT: We perform a systematic review of the literature to evaluate the role that zinc plays in epilepsy as well as the antiepileptic effect of zinc concentrations. Databases such as MEDLINE, EMBASE, SCISEARCH and LILACS were consulted from January 1974 to July 2005. All articles published in English and Spanish were considered. A manual review of the references present in each article was done in order to identify the articles that the electronic search may have not found itself. The title and abstract of the potential articles were analyzed before asking for the complete article. However, articles that seemed ambiguous were completely analyzed later to establish their relevance. CONCLUSIONS: Clinical research in epilepsy presented contradictory results. In fact, the reviewed studies, both animal and human, did not give enough evidence to determine if organic zinc variations are directly related to epilepsy. Most of them gave not statistically significant results.

[Changes in selenium levels in epilepsy]. / Alteración de la concentración de selenio en la epilepsia.

INTRODUCTION: It has been suggested that antiepileptic drug therapies deplete total body selenium stores and failure to give appropriate selenium supplementation, especially to patients receiving valproic acid during pregnancy may increase the risk of neural tube defects or other free radical mediated damage. Selenium is essential for the synthesis of selenoproteins, including glutathione peroxidase. AIMS: To review the present state of knowledge about selenium behaviour in people with epilepsy taking antiepileptic drugs and to develop guidelines for the appropriate use of selenium supplements. DEVELOPMENT: Databases such as Medline, Embase, Scisearch and Lilacs were consulted to have access to literature. A search in said databases was performed in order to find articles published from January 1966 to August 2004. All articles published in English and Spanish were considered. A manual review of the references present in each produced article was done in order to identify the articles that the electronic search may have not found itself. The title and abstract of the potential articles were analyzed before asking for the complete article. However, articles which seemed ambiguous were completely analyzed later to establish their relevance. CONCLUSIONS: There is insufficient evidence to fully evaluate the effect of selenium supplementation. The possible beneficial effects on pregnancy need to be evaluated in further studies.

Alteración de la concentración de selenio en la epilepsia / Changes in selenium levels in epilepsy

Introducción. Se ha sugerido que los tratamientos anticonvulsionantes disminuyen las reservas de selenio en el organismo y que no administrar suplementos de selenio, especialmente a las pacientes que reciben ácido valproico durante el embarazo, puede aumentar el riesgo de desarrollar defectos del tubo neural u otras alteraciones mediadas por radicales libres. El selenio es un oligoelemento esencial para la síntesis de selenoproteínas, incluida la glutatión peroxidasa. Objetivo. Realizar una revisión sistemática de la literatura para poder presentar el estado del conocimiento sobre el comportamiento del selenio en los pacientes con epilepsia en tratamiento anticonvulsionante y desarrollar unas recomendaciones para el uso adecuado de un suplemento de selenio. Desarrollo. Se consultaron las bases de datos Medline, Embase, Scisearch y Lilacs para acceder a la literatura, y se realizó una búsqueda para localizar artículos publicados entre enero de 1966 y agosto de 2004. Se tomaron todos los artículos publicados en inglés y español. Se realizó una revisión manual de las referencias presentadas en cada artículo con el fin de identificar los que no identificó la búsqueda electrónica. El título y el resumen de los artículos potencialmente útiles se analizaban antes de solicitar el artículo completo. Sin embargo, los artículos en los que éstos eran ambiguos para determinar su pertinencia también se analizaron en su totalidad. Conclusiones. No hay suficientes evidencias para evaluar el efecto de administrar un suplemento de selenio. El posible beneficio durante el embarazo requiere estudios más profundos

Introduction. It has been suggested that antiepileptic drug therapies deplete total body selenium stores and failure to give appropriate selenium supplementation, especially to patients receiving valproic acid during pregnancy may increase the risk of neural tube defects or other free radical mediated damage. Selenium is essential for the synthesis of selenoproteins, including glutathione peroxidase. Aims. To review the present state of knowledge about selenium behaviour in people with epilepsy taking antiepileptic drugs and to develop guidelines for the appropriate use of selenium supplements. Development. Databases such as Medline, Embase, Scisearch and Lilacs were consulted to have access to literature. A search in said databases was performed in order to find articles published from January 1966 to August 2004. All articles published in English and Spanish were considered. A manual review of the references present in each produced article was done in order to identify the articles that the electronic search may have not found itself. The title and abstract of the potential articles were analyzed before asking for the complete article. However, articles which seemed ambiguous were completely analyzed later to establish their relevance. Conclusions. There is insufficient evidence to fully evaluate the effect of selenium supplementation. The possible beneficial effects on pregnancy need to be evaluated in further studies

Modulation of rat liver cytochrome P450 by protein restriction assessed by biochemical and bacterial mutagenicity methods [corrected].

Protein restriction (PR) significantly inhibits spontaneous and chemical carcinogenesis. Several factors seem to be involved in this effect, including a decrease in body weight, cellular proliferation and DNA damage and an increase in antioxidant defenses. The current study was designed to determine modifications in some hepatic cytochromes P450 (CYPs) due to a hypoproteic diet and to investigate its implications on chemical mutagenesis. Western blot analysis showed decreases of 73, 40 and 74% in CYP1A, CYP2B and CYP2E1 protein concentrations in hepatic microsomes from animals fed a protein-restricted (6% protein) diet for 6 weeks in comparison with microsomes from rats fed a 24% protein diet during the same period. In the same way, low protein fed animals showed a 3.5-fold decrease in hepatic CYP1A1-associated ethoxyresorufin O-deethylase activity, a 6-fold decrease in CYP1A2-associated methoxyresorufin O-demethylase activity, a 1.7-fold decrease in CYP2B1-associated penthoxyresorufin O-dealkylase activity, a 9-fold decrease in CYP2B2-associated benzyloxyresorufin O-dealkylase and, finally, a 3.4-fold decrease in CYP2E1-associated 4-nitrophenol hydroxylase activity. As a result of decreased CYP hepatic protein concentrations and enzymatic activities, liver S9 from rats fed a hypoproteic diet was less efficient in activating promutagens than S9 prepared from rats fed a 24% protein diet in the Ames test. Mutagenic potency obtained with protein-restricted S9 was reduced 25-fold for 2-aminoanthracene, 1.5-fold for N-nitrosodipropylamine, 12.5-fold for N-nitrosodibutylamine, 2-fold for cyclophosphamide and N-nitrosopyrrolidine and 71-fold for N-nitrosodimethylamine. However, the mutagenic potency of benzo[a]pyrene was the same (4 revertants/ microg) with S9 derived from rats fed either a 6 or 24% protein diet.

Mutagenic activity of urban air samples and its modulation by chili extracts.

Different samples of ambient particulate organic matter were collected during the summer and winter of 1990 in Mexico City. After dichloromethane extraction, the samples were tested for mutagenicity with derivatives of Salmonella typhimurium possessing high activity of 'classical' nitroreductase (YG1021) or O-acetyltransferase (YG1024), and compared to the mutagenicity of the normal strain YG1020, and to that of a nitroreductase-deficient mutant TA98NR. The two enzyme-overproducing strains were more sensitive to the mutagenic effect of the extracts than the parent and deficient strains. The sensitivity order, i.e., YG1024 > YG1021 > YG1020 > TA98NR, emphasizes the usefulness of the new Salmonella strains in analyzing the mutagenicity of complex mixtures and suggests that some of the direct mutagenic compounds in the urban air samples are nitro-aromatics. Investigations were also conducted to analyze the effect of chili extract on the mutagenicity of an urban air sample. The extract itself showed moderate mutagenic activity and an additive effect was noted when both the chili and air extracts were present. On the other hand, the maximum volume of chili tested produced a decrease in the number of revertants without affecting the background lawn of bacterial growth. The same response was also observed when 1-nitropyrene, 1,6-dinitropyrene or 1,8-dinitropyrene was used as the genotoxic compound, although potentiation instead of addition occurred at low vegetable volumes. At the concentrations found in the chili extract, chlorophyllin and beta-carotene showed an antimutagenic effect against the nitro-aromatic compounds.

Mutagenic activity of 2-chloro-4-nitroaniline and 5-chlorosalicylic acid in Salmonella typhimurium: two possible metabolites of niclosamide.

Niclosamide is an anti-helminthic drug susceptible to being metabolized into a bacterial mutagen by the action of enzymes present in the S9 activation mixture. Additional results from genotoxic studies in rodents and humans suggest that the drug is absorbed from the gastrointestinal tract, and mutagenic metabolites are excreted both in the free form and as conjugated glucuronides. As in the case of other secondary amides, phase I metabolism of niclosamide may result in a hydrolytic cleavage of the amide bond, giving rise to 5-chlorosalicylic acid and 2-chloro-4-nitroaniline as the main metabolites. In this study, the mutagenicity of these compounds was tested using the Salmonella typhimurium assay. Bacterial mutagenicity tests with these 2 compounds reveal a non-mutagenic response with 5-chlorosalicylic acid and a mutagenic one with 2-chloro-4-nitroaniline. However, the mutagenic potency observed with this compound is lower than that of niclosamide. The role of nitroreduction in the activation of niclosamide and 2-chloro-4-nitroaniline was also investigated with the help of S. typhimurium strains TA98NR, YG1020, YG1021 and YG1024. The results show a pattern of response which is qualitatively similar for both compounds and this indicates that its mutagenicity depends on both nitroreduction and transacetylation.

[Cicatricial, antibacterial and antimycotic effects of tepescohuite in experimental animals]. / Efectos cicatrizante, antibacteriano y antimicótico del tepescohuite en animales de experimentación.

The cicatricial and antibacterial effects of the sterile powder of the barks of tepescohuite (Mimosa tenuiflora), 2% mupirocin ointment, and 0.9% saline were compared. The experiment was performed in rabbits with chemically induced burns clinically, histopathologically, bacteriologically, and mycologically controlled. No statistically significant difference was found among the three treatment modalities. Due to the potentially hepatotoxic effects and low therapeutic efficacy of tepescohuite it should not be used in human beings.

Risk of diarrhea during the first year of life associated with initial and subsequent colonization by specific enteropathogens.

The incidence of colonization by enteropathogenic, enterotoxigenic, enteroinvasive, and enterohemorrhagic Escherichia coli (detected by DNA hybridization with specific radiolabeled probes), Salmonella sp., Shigella sp., Campylobacter jejuni, and rotavirus was related to the presence of diarrhea in a cohort of 75 rural infants followed longitudinally during the first year of life. The study was carried out between August 1985 and February 1987 in the village of Lugar Sobre la Tierra Blanca, in the state of Morelos, 180 km southwest of Mexico City. Intestinal colonization by specific enteropathogens was followed with fecal cultures taken every fortnight and every time a child had diarrhea. Pathogens isolated from cultures taken in the 48 hours prior to the initiation of the diarrheal episode were considered to be associated with the disease. Diarrhea was detected in 82% of the children with initial isolation of enterohemorrhagic E. coli and in 64% of the children with enteropathogenic E. coli or Shigella sp. The risk of diarrhea associated with the initial isolation of other pathogens was lower, at 41% for rotavirus and approximately 25% for enterotoxigenic E. coli, Salmonella sp., and C. jejuni. Initial colonization by the enteropathogens studied, whether or not they were associated with diarrhea, prevented disease, but not colonization by the same organism, when the children were reinfected during the first year of life. Enteropathogenic E. coli adherence factor, human or porcine heat-stable enterotoxins, fimbrial colonization factor antigens, and Shiga-like toxins I and II were important pathogenic characteristics related to the presence of diarrhea and to protection against subsequent infection by the same organisms.

Prospective study of diarrhoeal disease in a cohort of rural Mexican children: incidence and isolated pathogens during the first two years of life.

Colonization of the intestine by putative pathogens was followed longitudinally in a cohort of 56 infants born during one calendar year in a rural Mexican village with faecal cultures taken every fortnight and every time a child had diarrhoea. The frequency of isolation of pathogens during episodes of diarrhoea was compared with that of matched controls from the same cohort. Incidence of diarrhoea during the first year of life was 98%, diminishing to 93% during the second year. The incidence curves for each year were not significantly different (P greater than 0.1). Isolation of enteropathogenic Escherichia coli, enterotoxigenic Escherichia coli producing heat-stable (ST) and/or heat-labile (LT) enterotoxins and rotaviruses was significantly higher in infants with diarrhoea during the first 2 years of life. In the case of shigella, although no significant differences were found by semester of life, 13 of 16 children in which these strains were found had diarrhoea. Isolation of Salmonella spp., Campylobacter spp. and protozoa were not significantly different in the two groups during the period studied. Strains showing localized adherence to HEp-2 cells or the presence of colonization factor antigens I or E8775 were found with significantly higher frequency in children with diarrhoea. Eighty-two percent of ST+ or LT+ ETEC strains isolated produced one of the three known colonization factors.

PIP: The incidence of diarrhea in the 1st 2 years of life and the pathogens isolated during these episodes were investigated in a longitudinal cohort study of the 56 infants born in March 1982-March 1983 in the rural Mexican Village of Stone Houses. Fecal cultures were taken every fortnight and at each episode of diarrhea. Overall, the incidence of diarrhea was 98% during the 1st year of life and 93% during the 2nd year. The average number of episodes of diarrhea per child was 3 during both years analyzed. Enteropathogenic Escherichia coli (EPEC) and enterotoxigenic E coli (ETEC) strains, along with rotaviruses and possibly shigella, were associated with 75% of cases of diarrhea in these children. With the exception of ETEC strains producing both heat-stable (HT) and heat-labile (LT) enterotoxins and rotaviruses, the frequency of isolation of other pathogens differed significantly by age group. While LT-producing ETEC strains were found throughout the 1st 2 years of life in both cases and controls, EPEC strains were only found in children under 18 months of age and always more frequently in those with diarrhea. Strains showing localized adherence to HEp-2 cells or the presence of colonization factor antigens I or E8775 were found with significantly higher frequency in children with diarrhea. 82% of ST+ or LT+ ETEC strains isolated produced 1 of the 3 known colonization factors. The results of this investigation can be used to develop a more appropriate biological approach to the prevention of childhood diarrheal disease. While vaccines against EPEC and ETEC should be administered during the 1st months of life or perhaps through the breast milk of immunized mothers, a rotavirus vaccine could be given at a later age.