ABSTRACT
Rifaximin is FDA-approved for treatment of irritable bowel syndrome with diarrhea (IBS-D), but poor solubility may limit its efficacy against microbes in the mucus layer, e.g. Escherichia coli. Here we evaluate adding the mucolytic N-acetylcysteine (NAC) to improve rifaximin efficacy. In a resazurin checkerboard assay, combining rifaximin with NAC had significant synergistic effects in reducing E. coli levels. The optimal rifaximin + NAC combination was then tested in a validated rat model of IBS-D (induced by cytolethal distending toxin [CdtB] inoculation). Rats were inoculated with vehicle and treated with placebo (Control-PBS) or rifaximin + NAC (Control-Rif + NAC, safety), or inoculated with CdtB and treated with placebo (CdtB-PBS), rifaximin (CdtB-Rifaximin), or rifaximin + NAC (CdtB-Rif + NAC) for 10 days. CdtB-inoculated rats (CdtB-PBS) developed wide variability in stool consistency (P = 0.0014) vs. controls (Control-PBS). Stool variability normalized in rats treated with rifaximin + NAC (CdtB-Rif + NAC) but not rifaximin alone (CdtB-Rifaximin). Small bowel bacterial levels were elevated in CdtB-PBS rats but normalized in CdtB-Rif + NAC but not CdtB-Rifaximin rats. E. coli and Desulfovibrio spp levels (each associated with different IBS-D microtypes) were also elevated in CdtB-inoculated (CdtB-PBS) but normalized in CdtB-Rif + NAC rats. Cytokine levels normalized only in CdtB-Rif + NAC rats, in a manner predicted to be associated with reduced diarrhea driven by reduced E. coli. These findings suggest that combining rifaximin with NAC may improve the percentage of IBS-D patients responding to treatment.
Subject(s)
Acetylcysteine , Diarrhea , Disease Models, Animal , Escherichia coli , Irritable Bowel Syndrome , Rifaximin , Animals , Rifaximin/pharmacology , Rifaximin/therapeutic use , Acetylcysteine/pharmacology , Acetylcysteine/administration & dosage , Rats , Escherichia coli/drug effects , Diarrhea/drug therapy , Diarrhea/microbiology , Irritable Bowel Syndrome/drug therapy , Irritable Bowel Syndrome/microbiology , Male , Rats, Sprague-Dawley , Drug Therapy, CombinationABSTRACT
INTRODUCTION: Gut microbiome changes are linked to obesity, but findings are based on stool data. In this article, we analyzed the duodenal microbiome and serum biomarkers in subjects with normal weight, overweight, and obesity. METHODS: Duodenal aspirates and serum samples were obtained from subjects undergoing standard-of-care esophagogastroduodenoscopy without colon preparation. Aspirate DNAs were analyzed by 16S rRNA and shotgun sequencing. Predicted microbial metabolic functions and serum levels of metabolic and inflammatory biomarkers were also assessed. RESULTS: Subjects with normal weight (N = 105), overweight (N = 67), and obesity (N = 42) were identified. Overweight-specific duodenal microbial features include lower relative abundance (RA) of Bifidobacterium species and Escherichia coli strain K-12 and higher Lactobacillus intestinalis , L. johnsonii , and Prevotella loescheii RA. Obesity-specific features include higher Lactobacillus gasseri RA and lower L. reuteri (subspecies rodentium ), Alloprevotella rava , and Leptotrichia spp RA. Escalation features (progressive changes from normal weight through obesity) include decreasing Bacteroides pyogenes , Staphylococcus hominis , and unknown Faecalibacterium species RA, increasing RA of unknown Lactobacillus and Mycobacterium species, and decreasing microbial potential for biogenic amines metabolism. De-escalation features (direction of change altered in normal to overweight and overweight to obesity) include Lactobacillus acidophilus , L. hominis , L. iners , and Bifidobacterium dentium . An unknown Lactobacillus species is associated with type IIa dyslipidemia and overweight, whereas Alloprevotella rava is associated with type IIb and IV dyslipidemias. DISCUSSION: Direct analysis of the duodenal microbiome has identified key genera associated with overweight and obesity, including some previously identified in stool, e.g., Bifidobacterium and Lactobacillus . Specific species and strains exhibit differing associations with overweight and obesity, including escalation and de-escalation features that may represent targets for future study and therapeutics.
Subject(s)
Gastrointestinal Microbiome , Obesity , Overweight , Humans , Obesity/microbiology , Female , Male , Overweight/microbiology , Middle Aged , Adult , Duodenum/microbiology , RNA, Ribosomal, 16S/genetics , Biomarkers/blood , Lactobacillus/isolation & purification , Bifidobacterium/isolation & purification , AgedABSTRACT
Diarrhea-predominant irritable bowel syndrome (IBS-D), associated with increased intestinal permeability, inflammation, and small intestinal bacterial overgrowth, can be triggered by acute gastroenteritis. Cytolethal distending toxin B (CdtB) is produced by gastroenteritis-causing pathogens and may underlie IBS-D development, through molecular mimicry with vinculin. Here, we examine the effects of exposure to CdtB alone on gut microbiome composition, host intestinal gene expression, and IBS-D-like phenotypes in a rat model. CdtB-inoculated rats exhibited increased anti-CdtB levels, which correlated with increased stool wet weights, pro-inflammatory cytokines (TNFα, IL2) and predicted microbial metabolic pathways including inflammatory responses, TNF responses, and diarrhea. Three distinct ileal microbiome profiles (microtypes) were identified in CdtB-inoculated rats. The first microtype (most like controls) had altered relative abundance (RA) of genera Bifidobacterium, Lactococcus, and Rothia. The second had lower microbial diversity, higher Escherichia-Shigella RA, higher absolute E. coli abundance, and altered host ileal tissue expression of immune-response and TNF-response genes compared to controls. The third microtype had higher microbial diversity, higher RA of hydrogen sulfide (H2S)-producer Desulfovibrio, and increased expression of H2S-associated pain/serotonin response genes. All CdtB-inoculated rats exhibited decreased ileal expression of cell junction component mRNAs, including vinculin-associated proteins. Significantly, cluster-specific microRNA-mRNA interactions controlling intestinal permeability, visceral hypersensitivity/pain, and gastrointestinal motility genes, including several previously associated with IBS were seen. These findings demonstrate that exposure to CdtB toxin alone results in IBS-like phenotypes including inflammation and diarrhea-like stool, decreased expression of intestinal barrier components, and altered ileal microtypes that influenced changes in microRNA-modulated gene expression and predicted metabolic pathways consistent with specific IBS-D symptoms.
Subject(s)
Gastroenteritis , Gastrointestinal Microbiome , Irritable Bowel Syndrome , Rats , Animals , Irritable Bowel Syndrome/genetics , Rodentia , Vinculin , Escherichia coli , Diarrhea , Inflammation , Gene Expression , PainABSTRACT
Studies using stool samples suggest that non-sugar sweetener (NSS) consumption affects gut microbiome composition. However, stool does not represent the entire gut. We analyzed the duodenal luminal microbiome in subjects consuming non-aspartame non-sugar sweeteners (NANS, N = 35), aspartame only (ASP, N = 9), and controls (CON, N = 55) and the stool microbiome in a subset (N = 40). Duodenal alpha diversity was decreased in NANS vs. CON. Duodenal relative abundance (RA) of Escherichia, Klebsiella, and Salmonella (all phylum Proteobacteria) was lower in both NANS and ASP vs. CON, whereas stool RA of Escherichia, Klebsiella, and Salmonella was increased in both NANS and ASP vs. CON. Predicted duodenal microbial metabolic pathways altered in NANS vs. CON included polysaccharides biosynthesis and D-galactose degradation, whereas cylindrospermopsin biosynthesis was significantly enriched in ASP vs. CON. These findings suggest that consuming non-sugar sweeteners may significantly alter microbiome composition and function in the metabolically active small bowel, with different alterations seen in stool.
ABSTRACT
Objetivo: caracterizar la demanda actual de Especialización en Terapia ocupacional (TO) en el Perú a través de las preferencias de los Terapeutas ocupacionales y las posibles áreas de interés. Material y Métodos: El estudio fue descriptivo transversal. Se aplicó una encuesta virtual a 177 Terapeutas ocupacionales del Perú, respondiendo un total de 11 preguntas y completando un consentimiento informado. Se utilizó el programa estadístico SPSS para el análisis de datos como herramienta estadística. Resultados: Los Terapeutas ocupacionales prefirieron las especialidades de Pediatría (22,2%) y Neurorrehabilitación (15,8%). La especialidad de salud mental y Rehabilitación de manos alcanzaron el 13,5%, mientras que Educación el 8,8%. La de menor preferencia fue geriatría alcanzando el 2,9%. Conclusiones: Las primeras especialidades de TO en ser creadas deberían ser Pediatría y neurorrehabilitación. Las temáticas en cada una de las especialidades merecen un análisis especifico. Sin embargo, es necesario aún crear un ámbito de debate puesto que las especialidades no deben enfocadas únicamente a aspectos biomédicos si no también a ámbitos sociales. (AU)
Objective: To characterize the current preference of Specialization in Occupational Therapy (OT) in Peru and the possible areas of interest. Material and Methods: The study was descriptive cross-sectional. An online survey was applied to 177 Occupational Therapists of Peru, responding a total of 11 questions and completing an informed consent. Descriptive and association statistics were used. Results: OT preferred the specialties of Paediatrics (22.2%) and Neurorehabilitation (15.8%). The specialty of mental health and hand rehabilitation reached 13.5%, while Education 8.8%. The least preferred was geriatrics. Conclusions: The first OT specialties to be created should be Paediatrics and neurorehabilitation. The themes in each of the specialties deserve specific analysis. However, it is still necessary to create an area for debate since specialties should not only focus on biomedical aspects but also on social areas.(AU)
Subject(s)
Humans , Male , Female , Pediatrics , Specialization , Occupational Therapy , Epidemiology, Descriptive , Cross-Sectional StudiesABSTRACT
Introducción y objetivos: La elevación de la creatinina es un marcador de riesgo en la insuficiencia cardíaca descompensada (ICD). Nuestro objetivo fue evaluar el rol pronóstico a largo plazo de la detección temprana de deterioro renal (DR), definido por elevación en los niveles de urea y/o creatinina, en pacientes con ICD. Material y métodos: Se incluyeron en forma prospectiva 241 individuos admitidos por ICD. Se seleccionaron los puntos de corte para urea y creatinina al ingreso a través de curva ROC, para la detección de eventos combinados (muerte o rehospitalización por ICD). El seguimiento medio fue de 366 ± 482 días. Resultados: La edad media fue 65,4 ± 11,6 años (63,8% hombres, 42,3% etiología isquémica) y la incidencia de eventos fue de 107. El área bajo curva ROC de urea y creatinina para la predicción de eventos fue de 0,59 y 0,57. Los puntos de corte, sensibilidad y especificidad fueron: urea 55 mg/dL, 57% y 63%; y creatinina 1,17 mg/dL, 58% y 62%, respectivamente. El DR se identificó en 144 (60,4%) sujetos, 82 con ambos marcadores elevados, 29 sólo con creatinina elevada y 33 sólo con urea elevada. En el grupo con DR fue más frecuente el diagnóstico previo de ICD (89 vs 78%, p=0,041) y la hipoperfusión periférica (12,5 y 4,1%, p=0,020), tuvieron menor fracción de eyección del ventrículo izquierdo (FEVI) (36,4±17,2% y 41,1±19,6%, p=0,05) y mayor nivel de pro-BNP (8681±9010 pg/l y 2943±269 pg/l, p<0,001). La supervivencia libre de rehospitalización por ICD a 18 meses en aquellos con y sin DR fue 35 y 60% (p=0,0086), y las variables asociadas con evolución adversa fueron DR (HR=1,8; IC 95% 1,1-2,7) y diagnóstico previo de ICD (HR=1,9; p<0,001; IC 95% 1,1-3,5). Conclusión: El uso combinado de urea y creatinina permite incrementar la detección temprana de DR en pacientes con ICD. Este hallazgo fue un fuerte predictor de eventos a largo plazo.
Background: Increased level of creatinine is a powerful risk marker in decompensated heart failure (DHF). Our objective was to evaluate the long-term prognostic role of early detection of renal dysfunction (RD), defined by abnormal levels of urea and/or creatinine, in patients with DHF. Patients and methods: Two hundred and forty-one patients admitted for DHF were prospectively included. The cut-off of urea and creatinine were selected using ROC curves for predicting combined events (death or rehospitalization for DHF). The mean follow-up was 366±482 days. Results: The mean age were 65.4±11.6 years (64% male, 42.3% ischemic etiology), and 44.4% had events. The area under ROC curves to predicting events for urea and creatinine was 0.59 and 0.57, respectively. The cut-off, sensitivity and specificity were: urea 55 mg/dL, 57% and 63%; creatinine 117 mg/dL, 58% and 62%, respectively. RD was identified in 144 (60.4%) subjects, 82 had elevated both markers, 29 with only increased levels of creatinine, and 33 with only abnormal levels of urea. RD groups had more frequently a previous diagnosis of HF (89 vs 78%, p=0.041) and peripheral hypoperfusion (12.5 vs 4.1%, p=0.020), and they showed lower LVEF (36.4±17.2% vs 41.1±19.6%, p=0.05) and higher pro-BNP (8.681±9010 pg/mL vs 2943±2690 pg/ mL, p<0.001) than those without RD. Eighteen-month free-DHF rehospitalization survival in patients with and without RD was 35% and 60% (p=0.0086). The variables significantly associated with events were RD (1.8, p<0.001; CI 95%=1.1-2.7) and previous diagnosis of HF (HR=1.9, CI 95%=1.1-3.5). Conclusion: The combined use of urea and creatinine improve the early detection of RD in patients with DHF. This finding was a strong long-term prognostic predictor.
Subject(s)
Humans , Heart Failure , Prognosis , Renal InsufficiencyABSTRACT
El complejo industrial ARCOR-Arroyito, en la Provincia de Cordoba, Argentina, esta constituido por siete unidades productivas de caramelos, turrones, sabores para la industria de la alimentacion, etcetera. Se describe la estrategia adoptada por la empresa para reducir el consumo de agua, ya que la facilidad con la que era obtenida de las napas condujo a un uso desmedido e irracional. Se destacan las acciones mas relevantes, los beneficios ambientales, y los beneficios economicos
Subject(s)
Argentina , Industrial Water Consumption , Water Consumption (Environmental Health) , Food-Processing Industry , Industry , Environment , Industrial WaterABSTRACT
El complejo industrial ARCOR-Arroyito, en la Provincia de Cordoba, Argentina, esta constituido por siete unidades productivas de caramelos, turrones, sabores para la industria de la alimentacion, etcetera. Se describe la estrategia adoptada por la empresa para reducir el consumo de agua, ya que la facilidad con la que era obtenida de las napas condujo a un uso desmedido e irracional. Se destacan las acciones mas relevantes, los beneficios ambientales, y los beneficios economicos
Subject(s)
Argentina , Water Consumption (Environmental Health) , Industrial Water Consumption , Industry , Industrial Water , Food-Processing Industry , EnvironmentSubject(s)
Humans , Male , Female , Adult , Middle Aged , Carotenoids/therapeutic use , Melanosis/drug therapy , Melanosis/epidemiology , Treatment Outcome , Vitamin A/therapeutic useSubject(s)
Humans , Male , Female , Adult , Middle Aged , Melanosis/drug therapy , Carotenoids/therapeutic use , Vitamin A/therapeutic use , Treatment Outcome , Melanosis/epidemiologyABSTRACT
Con el objeto de minimizar los efectos de la corrosión causados por incrustaciones o, capas de hierro y manganeso depositadas en las redes de distribución de agua potable, se desarrolla el presente trabajo basado en un método químico y en el uso de ácido cítrico, el que se caracteriza por sus propiedades acomplejantes y por ser además seguro en su manipuleo e inocuo para la salud
Subject(s)
Iron , Manganese , Water Purification , Chemical Phenomena , CongressABSTRACT
Con el objetivo de evaluar la prevalencia y algunas características de las reacciones adversas sistémicas a picadura de insectos himenopteros (abeja, avispas, hormiga) se estudió una población de 4061 personas elegidas al azar, por medio de un cuestionario protocolizado. Fueron estudiados 1665 (41 por ciento) hombres y 2396 (59 por ciento) mujeres, con edad promedio de 34 años y un rango de 3 a 85 años. 69,9 por ciento presentaron historia de picadura de himenópteros (47 por ciento abejas, 42 por ciento hormiga y 27 por ciento avispa). 16 por ciento de la muestra había sido picada por dos o más insectos. En los 4061 sujetos estudiados se observaron reacciones sistémicas en 155 para todos los insectos (3,8 por ciento). 83 sujetos lo fueron a picadura de abeja (2 por ciento), 20 a avispas (0,5 por ciento) y 52 (1,3 por ciento) a hormigas. La sintomatología consignada fue: urticaria y angioedema en todos los pacientes con reacciones sistémicas, como único síntoma en 64 por ciento y asociado con síntomas respiratorios cardiovasculares o gastrointestinales en 36 por ciento. Treinta y tres por ciento tuvieron síntomas respiratorios, pérdida de conocimiento en 8 por ciento y síntomas gastrointestinales en 7 por ciento. Entre los sujetos que recibieron picadura de himenóptero, 349/2836 (12,3 por ciento) requirió asistencia médica. En los pacientes que presentaron reacciones sistémicas, 123/155 (79,3 por ciento) requirió asistencia médica de urgencia. No se observó diferencia significativa, en relación a edad, sexo o residencia en medio rural o urbano. Se observó una tendencia no significativa de mayor prevalencia de reacciones sistémicas en personas que realizan tareas rurales. Se concluye que la picadura de himenópteros es un riesgo severo para la salud en Uruguay, con una alta prevalencia de reacciones sistémicas (80 por ciento de los afectados requirió asistencia médica). Los insectos más frecuentemente responsables fueron la abeja y la hormiga