RESUMO
Orally administered solid drug must dissolve in the gastrointestinal tract before absorption to provide a systemic response. Intestinal solubility is therefore crucial but difficult to measure since human intestinal fluid (HIF) is challenging to obtain, varies between fasted (Fa) and fed (Fe) states and exhibits inter and intra subject variability. A single simulated intestinal fluid (SIF) cannot reflect HIF variability, therefore current approaches are not optimal. In this study we have compared literature Fa/FeHIF drug solubilities to values measured in a novel in vitro simulated nine media system for either the fasted (Fa9SIF) or fed (Fe9SIF) state. The manuscript contains 129 literature sampled human intestinal fluid equilibrium solubility values and 387 simulated intestinal fluid equilibrium solubility values. Statistical comparison does not detect a difference (Fa/Fe9SIF vs Fa/FeHIF), a novel solubility correlation window enclosed 95% of an additional literature Fa/FeHIF data set and solubility behaviour is consistent with previous physicochemical studies. The Fa/Fe9SIF system therefore represents a novel in vitro methodology for bioequivalent intestinal solubility determination. Combined with intestinal permeability this provides an improved, population based, biopharmaceutical assessment that guides formulation development and indicates the presence of food based solubility effects. This transforms predictive ability during drug discovery and development and may represent a methodology applicable to other multicomponent fluids where no single component is responsible for performance.
Assuntos
Jejum , Absorção Intestinal , Solubilidade , Equivalência Terapêutica , Humanos , Absorção Intestinal/fisiologia , Preparações Farmacêuticas/química , Preparações Farmacêuticas/metabolismo , Jejum/metabolismo , Administração Oral , Mucosa Intestinal/metabolismo , Secreções Intestinais/química , Secreções Intestinais/metabolismo , PermeabilidadeRESUMO
The use of animal experiments can be minimized with computational models capable of reflecting the simulated environments. One such environment is intestinal fluid and the colloids formed in it. In this study we used molecular dynamics simulations to investigate solubilization patterns for three model drugs (carvedilol, felodipine and probucol) in dog intestinal fluid, a lipid-based formulation, and a mixture of both. We observed morphological transformations that lipids undergo due to the digestion process in the intestinal environment. Further, we evaluated the effect of bile salt concentration and observed the importance of interindividual variability. We applied two methods of estimating solubility enhancement based on the simulated data, of which one was in good qualitative agreement with the experimentally observed solubility enhancement. In addition to the computational simulations, we also measured solubility in i) aspirated dog intestinal fluid samples and ii) simulated canine intestinal fluid in the fasted state, and found there was no statistical difference between the two. Hence, a simplified dissolution medium suitable for in vitro studies provided physiologically relevant data for the systems explored. The computational protocol used in this study, coupled with in vitro studies using simulated intestinal fluids, can serve as a useful prescreening tool in the process of drug delivery strategies development.
Assuntos
Felodipino , Simulação de Dinâmica Molecular , Solubilidade , Cães , Animais , Felodipino/administração & dosagem , Felodipino/farmacocinética , Felodipino/química , Probucol/administração & dosagem , Probucol/farmacocinética , Probucol/química , Carvedilol/administração & dosagem , Carvedilol/farmacocinética , Carvedilol/química , Lipídeos/química , Líquidos Corporais/química , Líquidos Corporais/metabolismo , Ácidos e Sais Biliares/química , Masculino , Secreções Intestinais/químicaRESUMO
Human Salmonella infections pose significant public health challenges globally, primarily due to low diagnostic yield of systemic infections, emerging and expanding antibiotic resistance of both the typhoidal and non-typhoidal Salmonella strains and the development of asymptomatic carrier state that functions as a reservoir of infection in the community. The limited long-term efficacy of the currently licensed typhoid vaccines, especially in smaller children and non-availability of vaccines against other Salmonella serovars necessitate active research towards developing a multivalent vaccine with wider coverage of protection against pathogenic Salmonella serovars. We had earlier reported immunogenicity and protective efficacy of a subunit vaccine containing a recombinant outer membrane protein (T2544) of Salmonella Typhi in a mouse model. This was achieved through the robust induction of serum IgG, mucosal secretory IgA and Salmonella-specific cytotoxic T cells as well as memory B and T cell response. Here, we report the development of a glycoconjugate vaccine, containing high molecular weight complexes of Salmonella Typhimurium O-specific polysaccharide (OSP) and recombinant T2544 that conferred simultaneous protection against S. Typhi, S. Paratyphi, S. Typhimurium and cross-protection against S. enteritidis in mice. Our findings corroborate with the published studies that suggested the potential of Salmonella OSP as a vaccine antigen. The role of serum antibodies in vaccine-mediated protection is suggested by rapid seroconversion with high titers of serum IgG and IgA, persistently elevated titers after primary immunization along with a strong antibody recall response with higher avidity serum IgG against both OSP and T2544 and significantly raised SBA titers of both primary and secondary antibodies against different Salmonella serovars. Elevated intestinal secretory IgA and bacterial motility inhibition by the secretory antibodies supported their role as well in vaccine-induced protection. Finally, robust induction of T effector memory response indicates long term efficacy of the candidate vaccine. The above findings coupled with protection of vaccinated animals against multiple clinical isolates confirm the suitability of OSP-rT2544 as a broad-spectrum candidate subunit vaccine against human infection due to typhoidal and non-typhoidal Salmonella serovars.
Assuntos
Febre Tifoide , Vacinas Tíficas-Paratíficas , Criança , Humanos , Animais , Camundongos , Células T de Memória , Secreções Intestinais , Sorogrupo , Salmonella enteritidis , Vacinas de Subunidades Antigênicas , Imunoglobulina A Secretora , Imunoglobulina GRESUMO
<p><b>OBJECTIVE</b>To evaluate the application of small intestine double stoma and succus entericus reinfusion in the patients with severe intra-abdominal infection.</p><p><b>METHODS</b>Ten patients with high intestinal perforation from February 2005 to November 2014 were enrolled in the study. All the cases received emergency operation. Small bowel with intestinal perforation was resected, and double stoma was applied in the proximal and distal small intestine. When abdominal infection under control, total enteral nutrition was successfully administered from nasogastric tube. The succus entericus from the proximal intestine was collected and transfused back to the distal intestine. Stool was collected and fecal nitrogen, fat and carbohydrate contents were determined. Related serum protein levels were measured.</p><p><b>RESULTS</b>As compared to pre-reinfusion, the absorption rate of carbohydrate [(90.9±7.8)% vs. (82.7±15.2)%], fat [(87.6±6.4)% vs. (59.1±10.8)%], and nitrogen [(82.4±9.8)% vs. (67.2±15.4)%] increased after succus entericus reinfusion (P<0.05). The serum protein levels increased significantly as well[fibronectin: (285.6±3.6) vs. (157.0±22.6) mg/L, P<0.01; transferrin: (4.86±0.21) vs. (3.60±0.25) g/L, P<0.05; pre-albumin: (291.3±112.5) vs. (199.1±53.3) mg/L, P<0.05].</p><p><b>CONCLUSION</b>Small intestine double stoma and succus entericus reinfusion are effective in improving the absorption of carbohydrate, fat and nitrogen in the patients with severe intra-abdominal infection.</p>
Assuntos
Humanos , Nutrição Enteral , Perfuração Intestinal , Secreções Intestinais , Intestino Delgado , Infecções Intra-Abdominais , Estomas CirúrgicosRESUMO
BACKGROUND/AIMS: Lubiprostone, a chloride channel type 2 (ClC-2) activator, was thought to treat constipation by enhancing intestinal secretion. It has been associated with increased intestinal transit and delayed gastric emptying. Structurally similar to prostones with up to 54% prostaglandin E2 activity on prostaglandin E receptor 1 (EP1), lubiprostone may also exert EP1-mediated procontractile effect on intestinal smooth muscles. We investigated lubiprostone's effects on intestinal smooth muscle contractions and pyloric sphincter tone. METHODS: Isolated murine small intestinal (longitudinal and circular) and pyloric tissues were mounted in organ baths with modified Krebs solution for isometric recording. Basal muscle tension and response to electrical field stimulation (EFS; 2 ms pulses/10 V/6 Hz/30 sec train) were measured with lubiprostone (10(-10)-10(-5) M) +/- EP1 antagonist. Significance was established using Student t test and P < 0.05. RESULTS: Lubiprostone had no effect on the basal tension or EFS-induced contractions of longitudinal muscles. With circular muscles, lubiprostone caused a dose-dependent increase in EFS-induced contractions (2.11 +/- 0.88 to 4.43 +/- 1.38 N/g, P = 0.020) that was inhibited by pretreatment with EP1 antagonist (1.69 +/- 0.70 vs. 4.43 +/- 1.38 N/g, P = 0.030). Lubiprostone had no effect on circular muscle basal tension, but it induced a dose-dependent increase in pyloric basal tone (1.07 +/- 0.01 to 1.97 +/- 0.86 fold increase, P < 0.05) that was inhibited by EP1 antagonist. CONCLUSIONS: In mice, lubiprostone caused a dose-dependent and EP1-mediated increase in contractility of circular but not longitudinal small intestinal smooth muscles, and in basal tone of the pylorus. These findings suggest another mechanism for lubiprostone's observed clinical effects on gastrointestinal motility.
Assuntos
Animais , Humanos , Camundongos , Alprostadil , Banhos , Canais de Cloreto , Constipação Intestinal , Contratos , Dinoprostona , Esvaziamento Gástrico , Motilidade Gastrointestinal , Secreções Intestinais , Intestino Delgado , Soluções Isotônicas , Tono Muscular , Músculo Liso , Músculos , Piloro , Receptores de Prostaglandina E , Receptores de Prostaglandina E Subtipo EP1 , LubiprostonaRESUMO
<p><b>OBJECTIVE</b>To study the stability of costunolide (COS) and dehydrocostus lactone (DEH) of Vladimiriae Radix before and after being roasted in artificial gastric juice, artificial intestinal juice and isolated rat gastric, intestinal or colonic incubation juice.</p><p><b>METHOD</b>The HPLC method was used for the determination of the mass concentration of COS and DEH Vladimiriae Radix before and after being roasted artificial gastric juice, artificial intestinal juice and isolated rat gastric, intestinal or colonic incubation juice. The samples were incubated with isolated rat stomach, small intestine; colon was used to study physical adsorption, absorption or degradation parameters.</p><p><b>RESULT</b>COS of Vladimiriae Radix before or after being roasted was unstable in artificial gastric juice, with the average degradation constants as 0.758 0 and 0.531 1. Having been roasted, it showed an increasing stability with a significant difference (P < 0.01). Both of COS and DEH of Vladimiriae Radix before or after being roasted showed high adsorption, uptake or degradation (2 h), and it had significant difference between different parts.</p><p><b>CONCLUSION</b>COS was unstable in artificial gastric juice (unprocessed Vladimiriae Radix has a higher degradation rate). Isolated rat stomach, small intestine, colon can adsorb, take, degrade COS and DEH of Vladimiriae Radix before or after roasting process obviously and differently. It provides basis for studies on the absorption mechanisms of effective ingredients of Vladimiriae Radix before and after being roasted.</p>
Assuntos
Animais , Masculino , Ratos , Asteraceae , Química , Cromatografia Líquida de Alta Pressão , Colo , Metabolismo , Estabilidade de Medicamentos , Medicamentos de Ervas Chinesas , Química , Suco Gástrico , Química , Secreções Intestinais , Química , Intestinos , Metabolismo , Lactonas , Química , Farmacocinética , Plantas Medicinais , Química , Ratos Wistar , Sesquiterpenos , Química , Farmacocinética , Estômago , MetabolismoRESUMO
The three-step dissolution experiment was established to investigate the in vitro release of budesonide colon-specific tablet and to elucidate the drug release mechanism by fitting to different mathematical models. The physiological parameters of stomach, small intestine and colon such as pH value, intestinal flora, specific organic enzyme, vermiculation and conveying time were mimicked to plot the in vitro dissolution, separately. Sample were taken at predetermined time intervals in 24 h and the accumulated drug releases were determined by using HPLC method. Drug release curves of the localization tablets were fitted to various mathematical models. It shows that no drug release was found in 2 h. About 5% release was determined after 6 h while 77.5% accumulated release was reached within 24 h. Drug release from the in house formulation fitted well into first-order model. The three-step dissolution method could be used to evaluate the colon-specific characteristics of budesonide colonic localization tablet. The drug release behavior of the localization tablet conforms to the drug release mechanisms of controlled porosity osmotic pump where osmotic pressure is the main driving force for controlled delivery of drugs.
Assuntos
Animais , Ratos , Anti-Inflamatórios , Farmacocinética , Budesonida , Farmacocinética , Colo , Metabolismo , Preparações de Ação Retardada , Portadores de Fármacos , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Métodos , Excipientes , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Secreções Intestinais , Modelos Teóricos , ComprimidosRESUMO
<p><b>OBJECTIVE</b>To investigate the therapeutic mechanism of rhubarb in protecting the intestinal muco-membranous barrier in the mice.</p><p><b>METHOD</b>Bal b/c mice were divided into 2 groups, gavaged with normal saline and 10% rhubarb decoction, respectively. The animals were killed after 24 hours after the treatments. The intestinal juice was collected after intestinal lavage and centrifuged for determination of IgA, total protein, C3, high density lipoprotein, type II PLA2 activity, and content of lysozyme. At the same time, 40 mg of small intestine were incised in each mouse. Reverse transcription polymerase chain reaction (RT-PCR) and gel image analysis were performed to detect the content of the cryptdin gene expression.</p><p><b>RESULT</b>The content of IgA, total protein, the C3, lysozyme, and the type II PLA2 activity in intestinal lavaged juice exhibited the statistical differences between the two groups (P < 0.05). There were no significant difference in the ontents of HDL, cryptdin-1 and cryptdin-4 gene expression between the two groups (P > 0.05).</p><p><b>CONCLUSION</b>Rhubarb could increase secretion of several immune associated substances of the mucous membrane in normal intestine, indicating a possibility to abate the injury of intestine mucus resulted from severe stress induced by trauma, burn and shock. Through above mechanisms Rhubarb may also reduce the incidence of bacterial translocation and systemic inflammatory reaction syndrome (SIRS).</p>
Assuntos
Animais , Camundongos , Complemento C3 , Metabolismo , Medicamentos de Ervas Chinesas , Farmacologia , Fosfolipases A2 do Grupo II , Imunoglobulina A , Metabolismo , Mucosa Intestinal , Metabolismo , Secreções Intestinais , Metabolismo , Intestino Delgado , Metabolismo , Camundongos Endogâmicos BALB C , Muramidase , Metabolismo , Fosfolipases A , Metabolismo , Fosfolipases A2 , Plantas Medicinais , Química , Proteínas , Metabolismo , Rheum , QuímicaRESUMO
Aunque se ha postulado la posible existencia de portadores crónicos de Vibrio cholerae, la información al respecto es escasa y contradictoria. Con objeto de determinar la utilidad de la cuerda encapsulada (enterotest) para detectar V. cholerae en las secreciones duodenales de origen biliar (biliduodenales), se evaluó a 59 pacientes (30 hombres y 29 mujeres) mayores de 15 años con diagnóstico clínico y bacteriológico de cólera. Todos los pacientes, que fueron atendidos en el Hospital de apoyo Departamental María Auxiliadora en Lima, Perú, fueron sometidos al mismo esquema de rehidratación y recibieron 2 g diarios de tetraciclina por 3 días. De 1 a 7 días después de determinado el tratamiento con antibióticos se realizaron las primeras pruebas de control: cultivo de secreciones biliduodenales mediante enterotest y coprocultivo mediante hisopado rectal. Ningún paciente tenía diarrea en el primer control. El cultivo de secreciones biliduodenales dio resultados positivos a V. cholerae en cinco pacientes (8,5 por ciento) (cuatro mujeres y un hombre) y el coprocultivo dio resultados negativos en todos loa casos. Una semana después se repitieron las pruebas de control de los cinco pacientes. Todos los cultivos de secreciones bilidiodenales fueron negativos y solamente un coprocultivo fue positivo en esta etapa. La paciente en cuestión fue sometida a las mismas pruebas de control una semana más tarde y ambas fueron negativas. Concluimos que el enterotest puede ser un método simple, bien tolerado y de bajo costo para detectar portadores de V. cholerae (AU)
Assuntos
Vibrio cholerae/isolamento & purificação , Heterozigoto , Cólera/diagnóstico , Técnicas Bacteriológicas/estatística & dados numéricos , Secreções Intestinais/parasitologia , Peru/epidemiologiaRESUMO
Aunque se ha postulado la posible existencia de portadores crónicos de Vibrio cholerae, la información al respecto es escasa y contradictoria. Con objeto de determinar la utilidad de la cuerda encapsulada (enterotest) para detectar V. cholerae en las secreciones duodenales de origen biliar (biliduodenales), se evaluó a 59 pacientes (30 hombres y 29 mujeres) mayores de 15 años con diagnóstico clínico y bacteriológico de cólera. Todos los pacientes, que fueron atendidos en el Hospital de apoyo Departamental María Auxiliadora en Lima, Perú, fueron sometidos al mismo esquema de rehidratación y recibieron 2 g diarios de tetraciclina por 3 días. De 1 a 7 días después de determinado el tratamiento con antibióticos se realizaron las primeras pruebas de control: cultivo de secreciones biliduodenales mediante enterotest y coprocultivo mediante hisopado rectal. Ningún paciente tenía diarrea en el primer control. El cultivo de secreciones biliduodenales dio resultados positivos a V. cholerae en cinco pacientes (8,5 por ciento) (cuatro mujeres y un hombre) y el coprocultivo dio resultados negativos en todos loa casos. Una semana después se repitieron las pruebas de control de los cinco pacientes. Todos los cultivos de secreciones bilidiodenales fueron negativos y solamente un coprocultivo fue positivo en esta etapa. La paciente en cuestión fue sometida a las mismas pruebas de control una semana más tarde y ambas fueron negativas. Concluimos que el enterotest puede ser un método simple, bien tolerado y de bajo costo para detectar portadores de V. cholerae (AU)
Assuntos
Vibrio cholerae , Heterozigoto , Cólera , Técnicas Bacteriológicas , Peru , Secreções IntestinaisRESUMO
To investigate whether VacA (vacuolating toxin) produced by Helicobacter pylori Korean stain 99 induces intestinal secretion, purified VacA was added to T84 cell monolayers mounted in Ussing chambers, and electrical parameters were monitored. Mucosal addition of low pH-pretreated VacA increased short circuit current (Isc). The effect was time- and dose-dependent and saturable. The time-to-peak Isc was concentration-dependent. Chloride channel inhibitors, niflumic acid or 5- nitro-2- (3-phenylpropylamino) -benzoate (NPPB), inhibited VacA-stimulated Isc. Carbachol (CCh) -induced increase of Isc was prolonged by the addition of VacA to the mucosal side only. The effect was unaltered by the addition of niflumic acid. VacA did not show cytopathic effects. These studies indicate that VacA is a nonlethal toxin that acts in a polar manner on T84 monolayers to potentiate Cl secretion and the response to CCh secretion without decrease in monolayer resistance. VacA may contribute to diarrhea diseases in human intestinal epithelial cells.
Assuntos
Humanos , Carbacol , Canais de Cloreto , Diarreia , Células Epiteliais , Helicobacter pylori , Helicobacter , Secreções Intestinais , Ácido NiflúmicoRESUMO
Se plantea que el medio óptimo para la Giardia lamblia es en un pH entre 6,38 y 7,02. Los trofozoitos son intolerantes a un medio fuertemente ácido, y se ha informado la lisis de los trofozoitos de Giardiasis por el ácido clorhidrico. La estimulación con secretina creará las condiciones idóneas para poder aislar el parásito en el jugo duodenal. Se estudiaron 30 pacientes con diarreas crónicas; la casuística se dividio en dos grupos de 15 casos cada uno, y se utilizaron distintas técnicas de intubación, así como estimulación con secretina a distintas dosis. Se demostró que el método de estimulación con secretina para el diagnóstico de las giardiasis es de utilidad clínica en casos en los que este parásito no se aísle por métodos convecionales(AU)
Assuntos
Humanos , Criança , Giardíase/diagnóstico , Diarreia Infantil/etiologia , Giardia lamblia/isolamento & purificação , Intubação Gastrointestinal/métodos , Duodeno/parasitologia , Secreções Intestinais/parasitologia , SecretinaRESUMO
An important property of the intestine is the ability to secrete fluid. The intestinal secretion is regulated by a number of substances including vasoactive intestinal peptide (VIP), ATP and different inflammatory mediators. One of the most important secretagogues is adenosine during inflammation. However, the controversy concerning the underlying mechanism of adenosine-stimulated Cl- secretion in intestinal epithelial cells still continues. To investigate the effect of adenosine on Cl- secretion and its underlying mechanism in the rabbit colon mucosa, we measured short circuit current (ISC) under automatic voltage clamp with DVC-1000 in a modified Ussing chamber. Adenosine, when added to the basolateral side of the mucosa, increased ISC in a dose-dependent manner. The adenosine-stimulated ISC response was abolished when Cl- in the bath solution was replaced completely with gluconate. In addition, the ISC response was inhibited by a basolateral Na-K-Cl cotransporter blocker, bumetanide, and by apical Clchannel blockers, dephenylamine-2-carboxylate (DPC), 5-nitro-2-(3-phenyl-propylamino)-benzoate (NPPB), glibenclamide. Amiloride, an epithelial Na+ channel blocker, and 4,4-diisothiocyanato-stilbene-2,2-disulphonate (DIDS), a Ca2+-activated Cl- channel blocker, had no effect. In the mucosa pre-stimulated with forskolin, adenosine did not show any additive effect, whereas carbachol resulted in a synergistic potentiation of the ISC response. The adenosine response was inhibited by 10 micrometer H-89, an inhibitor of protein kinase A. These results suggest that the adenosine-stimulated ISC response is mediated by basolateral to apical Cl- secretion through a cAMP-dependent Cl- channel. The rank order of potencies of adenosine receptor agonists was 5'-(N-ethylcarboxamino)adenosine(NECA) > N6-(R-phenylisopropyl)adenosine(R-PIA)>2-(p-(2-carbonylethyl)-phenyl-et hylamino)-5'-N-ethylcarboxaminoadenosine(CGS21680). From the above results, it can be concluded that adenosine interacts with the A2b adenosine receptor in the rabbit colon mucosa and a cAMP-dependent signalling mechanism underlies the stimulation of Cl- secretion.
Assuntos
Adenosina , Trifosfato de Adenosina , Amilorida , Banhos , Bumetanida , Carbacol , Colforsina , Colo , Proteínas Quinases Dependentes de AMP Cíclico , Células Epiteliais , Glibureto , Inflamação , Secreções Intestinais , Intestinos , Mucosa , Agonistas do Receptor Purinérgico P1 , Receptores Purinérgicos P1 , Peptídeo Intestinal VasoativoRESUMO
Objetivo: analizar la validez de los anticuerpos antitransglutaminasa (tTGA) como marcador de la respuesta a la dieta libre de gluten (DLG) en pacientes celíacos y valorar la evolución de la hipertransaminasemia (HT) y ferropenia detectadas en el diagnóstico. Material y métodos: se analiza a 172 celíacos (141 niños, 31 adultos) en DLG. Se realiza control dietético-clínico, histológico, serológico y bioquímico. La valoración de tTGA se realizó utilizando anticuerpo recombinante humano. Resultados: tras un período en DLG (mediana 18 meses), 114 (81%) niños mostraron concentración normal de tTGA, 17 (12%) se mantuvieron en la zona gris y 10 (7%), valores elevados. En adultos las frecuencias eran 15 (48,3%), 11 (33,5%) y 5 (17,2%). Se realizaron 27 biopsias intestinales (26 niños, 1 adulto). La concordancia histológica con la concentración de tTGA fue elevada; índice kappa = 0,898 (0,72¿0,98). Se detectan trasgresiones en 7 pacientes (4 ocasionales, 3 frecuentes), de los cuales 6 presentaron tTGA elevada. El control de la DLG se realizó conforme a las recomendaciones establecidas en los niños, mientras que el 30% de los adultos diagnosticados de EC carece del mismo. En ambas poblaciones observamos disminución significativa de la HT y normalización de la ferropenia detectada al diagnóstico (p<0,001). Conclusiones: dado el acuerdo con los hallazgos histológicos, consideramos que la tTGA es un marcador indirecto útil para evaluar DLG al menos en población pediátrica. Sin embargo, no sustituye a la biopsia en casos de trasgresiones o de mala respuesta clínica. En nuestro medio es necesario concienciar al colectivo adulto de la importancia de la dieta y las complicaciones que conlleva su enfermedad sin tratar(AU)
Objective: To analyze the validity of antitransglutaminase antibodies (tTGA) as a serological marker of response to the gluten-free diet (GFD) in celiac patients and to determine the outcome of hypertransaminasemia (HT) and ferropenia found at the time of diagnosis. Material and methods: We have retrospectively analyzed the data from 172 patients with celiac disease (CD) (141 children and 31 adults) following a GFD. We have collected clinical and diet information and also histological, biochemical and serological data. The tTGA was measured with a human recombinant antibody. Results: After a median follow-up time of 1.5 years in GFD, 114 (81%) of the children had normal levels of tTGA, 17 (12%) showed values in the grey zone and only 10 (7%) had elevated levels of this marker. This contrasts with the figures found in adults, corresponding to 15 (48.3%), 11 (33.5%) and 5 (17.2%), respectively. In our series we have performed 27 intestinal biopsies during follow-up (26 children and 1 adult). The concordance rate between the results of this biopsy and the tTGA determination was high, with a Kappa Index ¼ 0.898. We have detected dietary transgressions in 7 patients (4 occasional and 3 frequently) and 6 of these 7 patients showed high levels of tTGA. The GFD was correctly followed by children according to the international recommendations, but only 40% of the adults followed the GFD adequately. In both populations we have found a significant decrease in HTand normalization of the ferropenia found at diagnosis (Po0.001). Conclusions: tTGA is a useful indirect marker for evaluation of GFD in a pediatric population, with a high concordance between serum levels of the marker and histological findings in the intestinal biopsy. However, tTGA cannot substitute biopsy in cases of diet transgressions or unfavourable clinical evolution. In our environment it is still essential to increase the awareness of the adult population regarding the importance of diet in CD and also of the serious complications associated with untreated disease(AU)
Assuntos
Humanos , Masculino , Feminino , Criança , Adulto , Doença Celíaca/dietoterapia , Doença Celíaca/diagnóstico , Imunoglobulina A , Glutens/análise , Glutens/metabolismo , Secreções Intestinais , Biópsia/métodos , Mucosa Intestinal , Sorologia/métodos , 28599Assuntos
Humanos , Nutrição Enteral , Nutrição Parenteral , Fístula do Sistema Digestório/terapia , Fístula do Sistema Digestório/metabolismo , Fístula do Sistema Digestório/mortalidade , Ingestão de Energia/fisiologia , Secreções Intestinais , Nitrogênio/administração & dosagem , Octreotida/uso terapêutico , Somatostatina/uso terapêutico , Vasoconstritores/uso terapêutico , Vitaminas/administração & dosagem , Equilíbrio Hidroeletrolítico/fisiologiaAssuntos
Humanos , Fístula do Sistema Digestório/terapia , Nutrição Enteral , Nutrição Parenteral , Fístula do Sistema Digestório/metabolismo , Fístula do Sistema Digestório/mortalidade , Ingestão de Energia/fisiologia , Secreções Intestinais , Nitrogênio/administração & dosagem , Octreotida/uso terapêutico , Somatostatina/uso terapêutico , Vasoconstritores/uso terapêutico , Vitaminas/administração & dosagem , Equilíbrio Hidroeletrolítico/fisiologiaRESUMO
El medio ácido disminuye la agregación plaquetaria y la formación del coágulo. El beneficio de los fármacos antisecretores en la hemorragia digestiva por enfermedad péptica (HDA-EP) se alcanzará, de forma ideal, al mantener un pH intragástrico superior 6 de forma constante. Los antagonistas H2 pierden su potencia antisecretora a partir del tercer día de tratamiento. Los inhibidores de la bomba de protones tienen una mayor capacidad antisecretora y más mantenida y han demostrado su eficacia en la prevención de la recidiva, necesidad de cirugía y mortalidad en la HDA-EP. Existen estudios demostrando la superioridad de omeprazol y pantoprazol frente a placebo, especialmente después de tratamiento endoscópico. Esomeprazol por vía intravenosa ha demostrado tener una mayor capacidad para inhibir la secreción ácida y elevar el pH intragástrico. Se recomienda un bolo de 80 mg, seguido de una infusión constante de 8 mg/hora durante tres días (AU)
In an acid environment platelet aggregation and clotting formation are reduced. Ideally, highest benefits in peptic disease- related digestive hemorrhages (PDRDH) could be reached if intragastric pH was continuously maintained above 6. The H2 antagonists lose their antisecretory potential after a three day treatment. The proton pump inhibitors have a higher and maintained antisecretory potential in comparison to H2 antagonists in PDRDH; their efficiency in the prevention of recurrent disease, reduction of surgery and mortality has been also demonstrated. Several studies have reported the superiority of omeprazole and pantoprazole compared to placebo, specially after endoscopic treatment. Intravenous esomeprazole has shown benefit preventing acid secretion and increasing intragastric pH. A bolus of 80 mg is the dose preferred, followed by constant infusion of esomeprazole 8 mg/hour throughout three days (AU)
Assuntos
Adulto , Humanos , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/patologia , Bombas de Próton/antagonistas & inibidores , Úlcera Péptica/complicações , Úlcera Péptica/etiologia , Secreções Intestinais/fisiologia , Secreções Intestinais , Fatores de RiscoRESUMO
Esomeprazol es un enantiómero del omeprazol (S-omeprazol). Es más potente que omeprazol para inhibir la secreción gástrica y produce un aumento más rápido del pH, manteniéndolo durante más tiempo por encima de 4. Esto permite que pueda ser utilizado a demanda para tratar a enfermos con enfermedad por reflujo gastroesofágico. Actúa bloqueando la ATPasa-H+/Na+ de la membrana de las células parietales gástricas. Se absorbe rápidamente en intestino delgado y en hígado se transforma por acción de las isoformas del citocromo P450 CYP2C19 y, en menor grado CYP34A, que actúan de forma distinta a como lo hacen con omeprazol lo que da lugar a una biodisponibilidad de esomeprazol mayor y una mayor área bajo la curva de la concentración plasmática. Es bien tolerado y disponible por vía intravenosa para administrar en inyección en 3 minutos o en infusión (AU)
Esomeprazole is an enantiomer of omeprazole (S-omeprazole). The gastric secretion suppression is better for esomeprazole in comparison with omeprazole; esomeprazole increases the pH faster, maintaining it above 4 during more time. Thus, it can be used on demand in patients with gastroesophagic reflux disease. The esomeprazole action pattern includes the blockade of H+/Na+ ATPase in the gastric parietal cell membrane. It is absorbed rapidly in the small bowel and transformed in the liver by the action of P450 CYP2C19 cytochrome isoenzymes and, in lesser extent, by P450 CYP34A cytochrome isoenzymes, as they perform in a different way with esomeprazole. This feature increases the esomeprazole bioavailability and the area under the plasmatic concentration curve. Esomeprazole is well tolerated and it can be administrated by intravenous injection or infusion (AU)
Assuntos
Omeprazol/farmacologia , Omeprazol/uso terapêutico , Refluxo Gastroesofágico/etiologia , Refluxo Gastroesofágico/prevenção & controle , Bombas de Próton/antagonistas & inibidores , Secreções Intestinais/fisiologiaRESUMO
Los habitantes de los Andes peruanos que moran por encima de 3,800 m.s.m.n presentan característicamente: I. Gran frecuencia del dolicomegacolon andino, que se acompaña de estreñimiento, distensión abdominal, elevación del hemidiafragma izquierdo evidenciable radiográficamente y alta incidencia del vólvulo, que constituye la primera causa de obstrucción intestinal en la altura. II. Un débito de secreción ácida gástrica basal mayor que a nivel del mar, con hiperrespuesta a la estimulación; pero alcanzando un débito de secreción gástrica post-estímulo similar al de los individuos del nivel del mar. En la mayor secreción gástrica basal influye, entre otros factores, la hipertonía vagal inducida por la hipoxia y la hipergastrinemía basal encontrada como característica del individuo de altura. En ellos la secreción gástrica disminuye mas tempranamente en relación con la edad y presentan mayor incidencia de úlcera y hemorragia gástrica.
Assuntos
Humanos , Altitude , Sistema Digestório , Obstrução Intestinal , Secreções Intestinais , PeruRESUMO
La lesión de la mucosa intestinal presente en niños con diarrea persistente condiciona un deficiencia de lactasa. Se realizó un ensayo clínico a doble ciegas, asigndasdose 40 niños menores de un año con idarrea persistente de forma aleatoria a 2 grupos, uno recibio leche libre de lactosa (SINLACTI) y el otro leche evaporada terciada. el número de éxito es tres veces mayor en los pacientes a los que se administró leche sin lactasa. sinlacti fue eficaz en el control de la diarrea. Se tuvieron en cuenta para el análisis de los resultados las sguientes variables: edad, estado nutricional, introducción precoz de la leche animal, episodios diarreicos previos, tratamiento con metronidazol y la etiología de la enfermedad diarreica. Los factores de riesgo evaluados no influeyeron significativamente en los resultados de ensayo.