Non-invasive biomagnetic assessment of gastrointestinal motility in a loperamide-induced constipation model

Constipation is a disorder of the gastrointestinal (GI) and some of the main etiological mechanisms are directly related to changes in GI physiology. The capacity to carry out paired assessments and measure GI parameters under the influence of constipation is a relevant point in selecting a suitable methodology. We aimed to perform a non-invasive investigation of gastrointestinal motility in constipated rats using the alternating current biosusceptometry system (ACB). The animals were split into two groups: the pre-induction stage (CONTROL) and post-induction loperamide stage (LOP). We assessed GI motility parameters using the ACB system. Colon morphometric and immunohistochemical analyses were performed for biomarkers (C-kit) for interstitial cells of Cajal (ICC). Our results showed a significant increase in gastrointestinal transit in the LOP group in addition to a reduction in the dominant frequency of gastric contraction and an arrhythmic profile. A change in colonic contractility profiles was observed, indicating colonic dysmotility in the LOP group. We found a reduction in the number of biomarkers for intestinal cells of Cajal (ICC) in the LOP group. The ACB system can evaluate transit irregularities and their degrees of severity, while also supporting research into novel, safer, and more efficient treatments for constipation.

The Mexican consensus on fecal incontinence.

Fecal incontinence is the involuntary passage or the incapacity to control the release of fecal matter through the anus. It is a condition that significantly impairs quality of life in those that suffer from it, given that it affects body image, self-esteem, and interferes with everyday activities, in turn, favoring social isolation. There are no guidelines or consensus in Mexico on the topic, and so the Asociación Mexicana de Gastroenterología brought together a multidisciplinary group (gastroenterologists, neurogastroenterologists, and surgeons) to carry out the «Mexican consensus on fecal incontinence¼ and establish useful recommendations for the medical community. The present document presents the formulated recommendations in 35 statements. Fecal incontinence is known to be a frequent entity whose incidence increases as individuals age, but one that is under-recognized. The pathophysiology of incontinence is complex and multifactorial, and in most cases, there is more than one associated risk factor. Even though there is no diagnostic gold standard, the combination of tests that evaluate structure (endoanal ultrasound) and function (anorectal manometry) should be recommended in all cases. Treatment should also be multidisciplinary and general measures and drugs (lidamidine, loperamide) are recommended, as well as non-pharmacologic interventions, such as biofeedback therapy, in selected cases. Likewise, surgical treatment should be offered to selected patients and performed by experts.

Luteolin ameliorates loperamide-induced functional constipation in mice.

Functional constipation (FC) is one of the most common gastrointestinal disorders characterized by hard stools and infrequent bowel movements, which is associated with dysfunction of the enteric nervous system and intestinal motility. Luteolin, a naturally occurring flavone, was reported to possess potential pharmacological activities on intestinal inflammation and nerve injury. This study aimed to explore the role of luteolin and its functional mechanism in loperamide-induced FC mice. Our results showed that luteolin treatment reversed the reduction in defecation frequency, fecal water content, and intestinal transit ratio, and the elevation in transit time of FC models. Consistently, luteolin increased the thickness of the muscular layer and lessened colonic histopathological injury induced by loperamide. Furthermore, we revealed that luteolin treatment increased the expression of neuronal protein HuC/D and the levels of intestinal motility-related biomarkers, including substance P (SP), vasoactive intestinal polypeptide (VIP), and acetylcholine (ACh), as well as interstitial cells of Cajal (ICC) biomarker KIT proto-oncogene, receptor tyrosine kinase (C-Kit), and anoctamin-1 (ANO1), implying that luteolin mediated enhancement of colonic function and contributed to the anti-intestinal dysmotility against loperamide-induced FC. Additionally, luteolin decreased the upregulation of aquaporin (AQP)-3, AQP-4, and AQP-8 in the colon of FC mice. In summary, our data showed that luteolin might be an attractive option for developing FC-relieving medications.

Uso de loperamida en pacientes pediátricos con falla intestinal por síndrome de intestino corto / Use of loperamide in pediatric patients with intestinal failure due to short bowel syndrome

INTRODUCCIÓN: Este documento técnico se realizó en el marco de la Guía de Práctica Clínica para pacientes pediátricos con falla intestinal; la pregunta PICO fue la siguiente: P: pacientes de 0-18 años con falla intestinal por síndrome de intestino corto; I: loperamida; C: no uso de loperamida o uso de otros antidiarreicos; O: reducción del débito del estoma, eventos adversos, sobrecrecimiento bacteriano. a) Cuadro clínico: La falla intestinal es la reducción de la función intestinal por debajo del mínimo necesario para la absorción de nutrientes y/o agua y electrolitos, requiriendo suplementación intravenosa para mantener la salud y/o crecimiento. El síndrome de intestino corto (SIC) es la principal causa de falla intestinal. En pacientes pediátricos, las causas más comunes de SIC incluyen enterocolitis necrotizante, gastrosquisis, vólvulo intestinal, atresia intestinal, íleo meconial complicado y aganglionosis. La incidencia global de SIC es aproximadamente 24,5 por 100.000 nacidos vivos por año. Las consecuencias relacionadas con el SIC incluyen diarrea, enfermedad hepática asociada a falla intestinal, colelitiasis, nefropatía por oxalatos, y acidosis d-láctica. La diarrea tiende a ser el síntoma más debilitante y suele producirse por un aumento de la motilidad intestinal, hipersecreción gástrica, disminución de la reserva de sales biliares, reducción de los mecanismos de retroalimentación de hormonas intestinales, y sobrecrecimiento de bacterias en el intestino delgado. b) Tecnología sanitaria: Loperamida es un derivado de la fenilpiperidina con acción agonista de los receptores opioides µ. Ejerce su acción antidiarreica sobre los receptores opioides intestinales ralentizando el tránsito intestinal mediante la reducción de la actividad muscular circular y longitudinal. Asimismo, puede ayudar a disminuir las secreciones ácidas gástricas, biliares y pancreáticas reduciendo el volumen de líquido en la luz intestinal que debe ser absorbido. Las reacciones adversas asociadas a su uso incluyen calambres, náuseas, dispepsia, somnolencia, fatiga, cansancio, mareos, dolor de cabeza y sequedad de boca. Las dosis recomendadas en niños con SIC se estiman en 0.4-0.8 mg/kg/día, hasta un máximo de 8 mg/día. En Perú, cuenta con 37 registros sanitarios vigentes y dos registros con vigencia prorrogada provisional, como denominación comercial y genérica, en dosis de 2 mg, y en forma de tabletas, tabletas masticables y cápsulas. El precio mínimo en establecimientos farmacéuticos privados asciende a S/. 0.07 y S/. 0.20 en establecimientos de salud públicos. OBJETIVO: Describir la evidencia científica disponible sobre la eficacia y seguridad de loperamida en pacientes pediátricos con falla intestinal asociada a síndrome de intestino corto. METODOLOGÍA: La búsqueda de evidencia se desarrolló en Medline, The Cochrane Library y LILACS hasta el 29 de agosto de 2021, limitado a estudios en español o inglés. La búsqueda de guías de práctica clínica (GPC) y evaluaciones de tecnología sanitaria (ETS) se desarrolló en repositorios digitales de agencias elaboradoras de estos documentos. La calidad metodológica se valoró usando la herramienta de la Colaboración Cochrane para estudios aleatorizados y Newcastle-Ottawa para estudios no aleatorizados. RESULTADOS: Se identificó cinco estudios y cinco GPC. No se identificaron estudios en población pediátrica, por lo que se consideró como evidencia indirecta a estudios desarrollados en población adulta. No se identificaron ETS, ni evaluaciones económicas realizadas en países de América Latina. Reducción del débito del estoma: Todos los estudios reportaron una disminución del débito del estoma durante el tratamiento con loperamida, comparado con placebo o no uso de antidiarreicos. Comparado con placebo, Kristensen & Qvist observaron una reducción de 16.5% (p<0.02), Tytgat reportó una disminución desde un volumen inicial de 660 gr. hasta un volumen final de 500 gr. (p<0.001) y el estudio de King reportó una disminución desde 633 + 253 gr. hasta 464 + 116 gr. (p<0.02). Comparado con el no uso de antidiarreicos, el estudio de Stevens reportó una reducción del 45% (p<0.0001), mientras que el estudio de Rodrigues observó una reducción desde un volumen inicial de 923 + 213 gr. hasta un volumen final de 847 + 167 gr. Finalmente, un estudio no reportó diferencias estadísticamente significativas entre codeína y loperamida (524 + 200 gr. vs. 464 + 116 gr, respectivamente). Eventos adversos: Tres estudios reportaron ningún evento adverso durante la terapia con loperamida. Un estudio reportó vómitos al cuarto día de administración de loperamida en un paciente, mientras que un estudio reportó dolor durante la apertura de la ileostomía por incremento de la consistencia de las heces en un paciente. Sobrecrecimiento bacteriano: Ningún estudio incluido reportó información sobre este desenlace. Recomendaciones en GPC: Dos GPC de ESPEN recomiendan el uso de loperamida. En la GPC sobre nutrición parenteral del 2009, se considera a loperamida como uso de primera línea, mientras que en la GPC del 2016 sobre el manejo de falla intestinal aguda se incluye el uso de loperamida y codeína fosfato. La GPC de Cleveland Clinic para el manejo de pacientes con síndrome de intestino corto recomienda el uso de antidiarreicos incluyendo a loperamida sin una preferencia explícita. La GPC de la BSC sobre manejo de pacientes con intestino corto incluye a loperamida para el tratamiento de la diarrea, pudiendo emplearse ocasionalmente codeína fosfato. Evaluación de la calidad metodológica: Todos los ensayos clínicos aleatorizados tuvieron riesgo de sesgo alto en al menos una dimensión evaluada. El único estudio no aleatorizado incluido obtuvo una calificación de cinco estrellas sobre un máximo de nueve posibles en la escala de Newcastle-Ottawa. El nivel de confianza de la evidencia mediante la metodología GRADE, fue consideró muy bajo para los desenlaces de debito del estoma y eventos adversos, por tratarse de evidencia indirecta y con alto riesgo de sesgo. CONCLUSIONES: No se encontró evidencia sobre la eficacia y seguridad de loperamida en pacientes pediátricos con falla intestinal por síndrome de intestino corto. La evidencia procedente de cinco estudios en adultos muestra que loperamida redujo significativamente el débito del estoma cuando se comparó con placebo o el no uso de antidiarreicos. Sin embargo, no se hallaron diferencias cuando se empleó como referencia un comparador activo como codeína. Los eventos adversos asociados a loperamida fueron leves y relativamente poco frecuentes, con tres estudios que reportaron ningún evento adverso durante el periodo de observación. No se encontró evidencia que evalúe el sobrecrecimiento bacteriano. Los estudios incluidos tuvieron alto riesgo de sesgo e importantes limitaciones metodológicas, destacando un seguimiento corto (entre 1 y 7 días), y un reducido número de participantes (entre 6 y 22). El nivel de confianza de la evidencia fue considerado muy bajo. Las cinco GPC incluidas en el presente informe coinciden en recomendar el uso de loperamida, al igual que otros medicamentos antidiarreicos, para reducir la motilidad y pérdidas intestinales en pacientes con falla intestinal por síndrome de intestino corto.

State-dependent inhibition of BK channels by the opioid agonist loperamide.

Large-conductance Ca2+-activated K+ (BK) channels control a range of physiological functions, and their dysfunction is linked to human disease. We have found that the widely used drug loperamide (LOP) can inhibit activity of BK channels composed of either α-subunits (BKα channels) or α-subunits plus the auxiliary γ1-subunit (BKα/γ1 channels), and here we analyze the molecular mechanism of LOP action. LOP applied at the cytosolic side of the membrane rapidly and reversibly inhibited BK current, an effect that appeared as a decay in voltage-activated BK currents. The apparent affinity for LOP decreased with hyperpolarization in a manner consistent with LOP behaving as an inhibitor of open, activated channels. Increasing LOP concentration reduced the half-maximal activation voltage, consistent with relative stabilization of the LOP-inhibited open state. Single-channel recordings revealed that LOP did not reduce unitary BK channel current, but instead decreased BK channel open probability and mean open times. LOP elicited use-dependent inhibition, in which trains of brief depolarizing steps lead to accumulated reduction of BK current, whereas single brief depolarizing steps do not. The principal effects of LOP on BK channel gating are described by a mechanism in which LOP acts as a state-dependent pore blocker. Our results suggest that therapeutic doses of LOP may act in part by inhibiting K+ efflux through intestinal BK channels.

Thallium-sensitive fluorescent assay reveals loperamide as a new inhibitor of the potassium channel Kv10.1.

BACKGROUND: Ion channels have been proposed as therapeutic targets for different types of malignancies. One of the most studied ion channels in cancer is the voltage-gated potassium channel ether-à-go-go 1 or Kv10.1. Various studies have shown that Kv10.1 expression induces the proliferation of several cancer cell lines and in vivo tumor models, while blocking or silencing inhibits proliferation. Kv10.1 is a promising target for drug discovery modulators that could be used in cancer treatment. This work aimed to screen for new Kv10.1 channel modulators using a thallium influx-based assay. METHODS: Pharmacological effects of small molecules on Kv10.1 channel activity were studied using a thallium-based fluorescent assay and patch-clamp electrophysiological recordings, both performed in HEK293 stably expressing the human Kv10.1 potassium channel. RESULTS: In thallium-sensitive fluorescent assays, we found that the small molecules loperamide and amitriptyline exert a potent inhibition on the activity of the oncogenic potassium channel Kv10.1. These results were confirmed by electrophysiological recordings, which showed that loperamide and amitriptyline decreased the amplitude of Kv10.1 currents in a dose-dependent manner. Both drugs could be promising tools for further studies. CONCLUSIONS: Thallium-sensitive fluorescent assay represents a reliable methodological tool for the primary screening of different molecules with potential activity on Kv10.1 channels or other K+ channels.

Poloxamer 188-Coated Ammonium Methacrylate Copolymer Nanocarriers Enhance Loperamide Permeability across Pgp-Expressing Epithelia.

Loperamide is a µ-opioid agonist with poor gastrointestinal absorption, mainly because of its modest aqueous solubility and being a P-glycoprotein (Pgp) efflux substrate. Nevertheless, studies associated with therapeutic effects strongly suggest that loperamide holds potential pharmacological advantages over traditional µ-opioid agonists commonly used for analgesia. Thus, in this Communication, we assessed in MDCK-hMDR1 cell lines the effects over loperamide uptake and efflux ratio, when loaded into Eudragit RS (ERS) nanocarriers coated with poloxamer 188 (P188). ERS was chosen for enhancing loperamide aqueous dispersibility and P188 as a potential negative Pgp modulator. In uptake assays, it was observed that Pgp limited the accumulation of loperamide into cells and that preincubation with P188, but not coincubation, led to increasing loperamide uptake at a similar extent of Pgp pharmacological inhibition. On the other hand, the efflux ratio displayed no alterations when Pgp was pharmacologically inhibited, whereas ERS/P188 nanocarriers effectively enhanced loperamide uptake and absorptive transepithelial transport. The latter suggests that loperamide transport across cells is significantly influenced by the presence of the unstirred water layer (UWL), which could hinder the visualization of Pgp-efflux effects during transport assays. Thus, results in this work highlight that formulating loperamide into this nanocarrier enhances its uptake and transport permeability.

Probióticos en el síndrome de intestino irritable con predominio de diarrea / Probiotics for the treatment of diarrhea predominant irritable bowel syndrome

Una mujer de 36 años, diagnosticada con síndrome de intestino irritable a predominio de diarrea (SII-D) acude a la consulta médica. Ella pregunta si el uso de probióticos sería útil para controlar los episodios de diarrea, ya que los fármacos con los que está siendo tratada no le resultan eficaces. Se realizó una búsqueda bibliográfica con el objetivo de en contrar evidencia en respuesta a su consulta, tras la cual se seleccionaron dos ensayos clínicos y una revisión sistemática. Se evidenciaron diversos resultados en cuanto al uso de probióticos en el SII-D y se discutieron los riesgos y beneficios del tratamiento, así como las implicancias en la vida de la paciente. (AU)

A 36-year-old woman diagnosed with diarrhea predominant irritable bowel syndrome (D-IBS) goes to meet the doctor. She raises whether the use of probiotics would be useful for controlling diarrhea episodes, since the drugs which she is being treated with, are not effective. A bibliographic search was conducted with the objective of finding evidence in response toher query. Two clinical trials and a systematic review were found. Variable results were found regarding the use of probioticsin D-IBS. The risks and benefits of the treatment were discussed, as well as the implications in the patient's lifestyle. (AU)

An Alternative Treatment Against Acanthocephala ( Prosthenorchis elegans) in Captive Squirrel Monkeys ( Saimiri sciureus) in Mexico.

We provide the first report of Acanthocephala ( Prosthenorchis elegans) in Mexican non-human primates. There has been no known treatment against this parasite except for surgical removal, and this has been relatively ineffective because of the small juveniles. We report the presence of P. elegans in a captive breeding colony of squirrel monkeys ( Saimiri sciureus) in Mexico, and we describe a successful treatment protocol. Treatment involved 2 steps: oral administration of the drugs loperamide chlorhydrate (0.5 mg/0.9 kg/3 days) and niclosamide (0.2 mg/0.9 kg/3 days) followed by surgical removal of adult worms from the intestine. Fecal examination during treatment revealed live adults but no living juveniles and no eggs. Surgery after 1 wk of treatment revealed the presence of adults and an absence of juvenile parasites. All adults were physically extracted during the surgery. All subjects recovered from surgery within 1 wk.

Loperamida en el manejo de ileostomía de alto débito. A propósito de un caso / Loperamide in the management of high-debit ileostomy. About a case

Introducción: La Ostomía de Alto Débito es una complicación frecuente y poco identificada. Se recomienda la utilización de loperamida. Sin embargo, es una indicación off label.Paciente femenino de 78 años con antecedente de una ileostomía por cáncer de colon derecho, internada por sepsis en terapia intensiva. Presenta abundante débito por ileostomía permeable.Se acuerda con médico tratante y equipo de soporte nutricional iniciar nutrición enteral y loperamida. La paciente evoluciona favorablemente y normaliza el débito.Algunos profesionales, deciden suspender la loperamida y otros disminuir la frecuencia. La paciente aumenta nuevamente la producción del débito.Se justifica el propósito de la intervención con evidencia científica y se optimiza la comunicación interdisciplinaria para asegurar la dosificación que optimiza el tratamiento. Evoluciona de forma favorable y es dada de alta. Objetivo: Destacar la importancia del trabajo interdisciplinario para el abordaje de complicaciones, dando a conocer un tratamiento efectivo en ileostomías de alto débito.Discusión:La información publicada en relación con el uso de loperamida para esta indicación es escasa. El tratamiento sigue siendo basado en la observación y la experiencia de los expertos en los centros especializados.En cuanto a la seguridad de instaurar el tratamiento, evaluando que los efectos adversos cardíacos no han sido reportados en éstos pacientes, y que éstos presentan mayor riesgo de tener eventos cardíacos secundarios a los trastornos hidroelectrolíticos concomitantes de la misma patología de base, se decidió avalar laconducta de la indicación de loperamida que mostró mejor riesgo-beneficio con respecto a la no indicación. La comunicación interdisciplinaria impacta en la mejoría clínica del paciente y en la calidad de atención brindada

ntroduction: High-output Ostomy is a frequent and poorly identified complication. The use of loperamide is recommended. However, it is an off label indication.A 78-year-old female patient with a history of an ileostomy due to right colon cancer hospitalized for sepsis in intensive care. It has an abundant flow rate due to permeable ileostomy.It is agreed with treating physician and nutritional support team to initiate enteral nutrition and loperamide. The patient progresses favorably and normalizes th flow rate.Some professionals, decide to suspend loperamide and others decrease the frequency. The patient again increases the output of the flow.The purpose of the intervention with scientific evidence is justified and the interdisciplinary communication is optimized to ensure the dosage that optimizes the treatment. Evolves favorably and is discharged.Objective: Highlight the importance of interdisciplinary work in the management of complications, revealing an effective treatment in high-output ileostomies.Discussion: The published information regarding the use of loperamide for this indication is scarce. Treatment is still based on the observation and experience of experts in specialized centers.As regard the safety of establishing the treatment, evaluating that cardiac adverse effects have not been reported in these patients, and that they are at increased risk of having cardiac events secondary to the concomitant hydroelectrolytic disorders of the same underlying disease, it was decided to endorse The behavior of the indication of loperamide that showed better risk-benefit with respect to no indication.Interdisciplinary communication impacts on the clinical improvement of the patient and on the quality of care provided

Trial Evaluating Ambulatory Therapy of Travelers' Diarrhea (TrEAT TD) Study: A Randomized Controlled Trial Comparing 3 Single-Dose Antibiotic Regimens With Loperamide.

BACKGROUND: Recommended treatment for travelers' diarrhea includes the combination of an antibiotic, usually a fluoroquinolone or azithromycin, and loperamide for rapid resolution of symptoms. However, adverse events, postdose nausea with high-dose azithromycin, effectiveness of single-dose rifaximin, and emerging resistance to front-line agents are evidence gaps underlying current recommendations. METHODS: A randomized, double-blind trial was conducted in 4 countries (Afghanistan, Djibouti, Kenya, and Honduras) between September 2012 and July 2015. US and UK service members with acute watery diarrhea were randomized and received single-dose azithromycin (500 mg; 106 persons), levofloxacin (500 mg; 111 persons), or rifaximin (1650 mg; 107 persons), in combination with loperamide (labeled dosing). The efficacy outcomes included clinical cure at 24 hours and time to last unformed stool. RESULTS: Clinical cure at 24 hours occurred in 81.4%, 78.3%, and 74.8% of the levofloxacin, azithromycin, and rifaximin arms, respectively. Compared with levofloxacin, azithromycin was not inferior (P = .01). Noninferiority could not be shown with rifaximin (P = .07). At 48 and 72 hours, efficacy among regimens was equivalent (approximately 91% at 48 and 96% at 72 hours). The median time to last unformed stool did not differ between treatment arms (azithromycin, 3.8 hours; levofloxacin, 6.4 hours; rifaximin, 5.6 hours). Treatment failures were uncommon (3.8%, 4.4%, and 1.9% in azithromycin, levofloxacin, and rifaximin arms, respectively) (P = .55). There were no differences between treatment arms with postdose nausea, vomiting, or other adverse events. CONCLUSIONS: Single-dose azithromycin, levofloxacin, and rifaximin with loperamide were comparable for treatment of acute watery diarrhea. CLINICAL TRIAL REGISTRATION: NCT01618591.

Is it worth adding loperamide to antibiotic treatment of traveler’s diarrhea? / ¿Vale la pena agregar loperamida al tratamiento antibiótico de la diarrea del viajero?

Travelers' diarrhea is a frequent condition, especially in those traveling to high-risk areas. Although antibiotic treatment reduces the duration of diarrhea, it has been suggested adding loperamide could further reduce the symptoms. To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We identified two systematic reviews including 28 studies overall, of which 15 were randomized trials relevant for the question of interest. We extracted data from the systematic reviews, reanalysed data of primary studies and generated a summary of findings table using the GRADE approach. We concluded adding loperamide to antibiotic treatment might accelerate resolution of symptoms in traveler’s diarrhea with minimal or no adverse effects.

La diarrea del viajero es una patología frecuente, en especial en quienes se dirigen a regiones de alto riesgo. Si bien el tratamiento antibiótico reduce la duración del cuadro, se ha planteado que la asociación de loperamida podría reducir aún más los síntomas. Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Identificamos dos revisiones sistemáticas que en conjunto incluyen 28 estudios primarios, de los cuales 15 corresponden a ensayos aleatorizados. Extrajimos los datos desde las revisiones identificadas y preparamos tablas de resumen de los resultados utilizando el método GRADE. Concluimos que agregar loperamida al tratamiento con antibióticos podría acelerar la resolución del cuadro, sin asociarse probablemente a efectos adversos importantes.

Interacciones farmacológicas de las hojas de Maytenus macrocarpa o ôchuchuhuasiõ con fármacos inhibitorios y estimuladores de la motilidad intestinal / Pharmacological interactions from the leaves of Maytenus macrocarpa \"chuchuhuasi\" with inhibitory and stimulating bowel motility drugs

Objetivo: Determinar las posibles interacciones farmacológicas de las hojas de Maytenus macrocarpa, con fármacos estimulantes e inhibitorios de la motilidad intestinal. Métodos: Se utilizaron 110 ratones albinos machos, con pesos medios de 25 g, se empleó el método de Arbos y col, se administró carbón activado al 5

vía oral, dosis de 0.1ml/10g, como marcador intestinal. Los grupos experimentales fueron: control (agua destilada 0,3ml), hojas de chuchuhuasi 1 (500mg/kg), hojas de chuchuhuasi 2 (3000mg/kg), atropina (1,5mg/kg), loperamida (5mg/kg), neostigmina (0,4mg/kg), metoclopramida (10mg/kg), hojas de chuchuhuasi 1 con metoclopramida, hojas de chuchuhuasi 1 con loperamida, hojas de chuchuhuasi 2 con metoclopramida y hojas de chuchuhuasi 2 con loperamida. Para la validación estadística se usó la prueba de Wilconxon, ANOVA y Tukey. Resultados: El porcentaje de recorrido intestinal de carbón activado fue de 27,04, 34,15, 31,66, 25,57, 15,89, 43,30, 33,99, 32,40, 27,90, 49,34 y 25,36 respectivamente, el test de ANOVA de dos colas revelo una p=0,0007. El test de Tukey indico p<0.05 versus el control para neostigmina, loperamida y la interacción chuchuhuasi 3000 mg/kg con metoclopramida, en este último, el test de Wilconxon presento un valor p<0,05. Conclusiones: Se observó interacciones farmacológicas de antagonismo sobre la motilidad intestinal, entre chuchuhuasi y Loperamida y sinergismo entre chuchuhuasi y metoclopramida.

Objectives: To determine the possible pharmacological interactions from the leaves of Maytenus macrocarpa with inhibitory and stimulating bowel motility drugs. Methods: We used 110 male albino mice with average weight of 25g, Arbos and others method was applied. Activated charcoal was administered at 5

at dose of 0.1ml/10g, as an intestinal marker. The experimental groups included 0.1 ml/10 g of distilled water, leave extract of M. macrocarpa 1 (500mg/kg), leave extract of M. macrocarpa 2 (3000 mg/kg), 1,5mg/kg of atropine, 5mg/kg of loperamide, 0.4mg/kg of neostigmine, 10mg/kg of metoclopramide, leave extract of M. macrocarpa 1 with metoclopramide, leave extract of M. macrocarpa 1 with loperamide, leave extract of M. macrocarpa 2 with metoclopramide and leave extract of M. macrocarpa 2 with loperamide. The statistical validation was based on Wilconxon, ANOVA and Tukey test. Results: The intestinal charcoal run percentage was 27.04, 34.15, 31.66, 25.57, 15.89, 43.30, 33.99, 32.40, 27.9, 49.34 and 25.36 respectively. The ANOVA test result in p= 0.0007. The Tukey test indicated p <0.05 versus the control group for neostigmine, loperamide, and the interaction between leave extract of M. macrocarpa 2 with metoclopramide, for the last the Wilcoxon test result in p <0.05. Conclusions: It was observed antagonism drug interactions on gastrointestinal motility between leaves extract of M. macrocarpa with loperamide and synergism interactions with metoclopramide.

Diarrea del viajero / Traveler's diarrhea

La diarrea del viajero es una de las condiciones que con mayor frecuencia afecta a los viajeros de países industrializados que visitan las zonas tropicales y subtropicales del planeta. El 20 a 50% de viajeros se van afectar por esta condición, siendo en ocasiones tan severa como para afectar los planes del viajero en la quinta parte de pacientes. El cuadro se manifiesta por la aparición de diarrea asociada a síntomas entéricos como dolor abdominal, nauseas, vómitos y en caso de diarrea inflamatoria fiebre y deposiciones con sangre. Entre los agentes etiológicos bacterianos más frecuentes están Escherichia coli enterotoxigénica, Salmonella, Shigella, entre otros agentes, aunque en cerca de la mitad de los casos no se aísla un agente etiológico. En caso de diarrea persistente debe descartarse parásitos y en zonas endémicas debe realizarse las pruebas especiales para descartar infección por Cyclospora cayetanensis. En pacientes con diarrea del viajero está indicado el manejo empírico con antibióticos, lo cual disminuye la duración de la enfermedad. En ausencia de fiebre o diarrea con sangre puede usarse loperamida. La prevención es importante en especialmente en pacientes de alto riesgo o en quienes sea importante que no se afecte el viaje.

TravelersÆ diarrhea is one of the most common conditions that affect travelers from industrialized countries who visit tropical and subtropical areas of the world. Twenty to fifty percent of travelers will suffer from this condition, and one fifth of these subjects will have diarrhea severe enough to affect their travel plans. Illness is characterized by the occurrence of diarrhea, associated with other gastrointestinal symptoms such as abdominal pain, nausea, vomiting and sometimes, in association of inflammatory diarrhea, fever and bloody stools. Among the most common etiologic agents Enterotoxigenic Escherichia coli, Salmonella, and Shigella are among the most common bacterial pathogens, although in close to one half of cases culture results are negative. In cases of persistent diarrhea parasites must be ruled out, and in endemic areas special stains must be ordered to rule agents like Cyclospora cayetanensis. In patients with TravelersÆ diarrhea empiric treatment with antibiotics is indicated, reducing the duration of illness. In the absence of fever or bloody diarrhea loperamide can be used. Prevention is important, especially in high risk patients or those in whom the trip must not be affected by the illness.

Diarreia aguda / Acute diarrhea

Diarreia aguda é a passagem de quantidade acima do normal de fezes amolecidas associada ao aumento do número de evacuações. No diagnóstico diferencial das diarreias agudas devem ser enfocados as infecções, as alergias alimentares, a intoxicação alimentar, o uso de medicações e a apresentação inicial de diarreia crônica. Dentre estas possíveis etiologias, especialmente em nosso meio, as causas infecciosas devem sempre vir à mente e constituir uma das primeiras opções na investigação diagnóstica. As infecções intestinais associadas a quadros diarreicos são a segunda causa de mortes de origem infecciosa em todo o mundo, com prevalência estimada de 3 a 5 bilhões de casos/ano. Os autores atualizam as novidades e peculiaridades a respeito do diagnóstico e dos tratamentos - geral e/ou específico - dos diferentes agentes associados à diarreia aguda infecciosa

Acute diarrhea is the passage of above normal quantities of soft faeces also associated with increased bowel movements. Differential diagnosis of acute diarrhea should be focused on infections, food allergies, food poisoning, use of medications and the initial presentation of chronic diarrhea. Among these possible etiologies, given the environment we live in, infectious causes should always be taken into account and be one of the first options in dignostic investigation. Intestinal infections associated with diarrheal frames are the second leading cause of infectious deaths worldwide, with an estimated to 3-5 billion cases/per year. In this review, the authors inted to review the new features and aspects concerning diagnosis and treatment - general and/or specific - of the different agents associated with acute infectious diarrhea