Qual é a influência da microbiota na obesidade e em seu quadro inflamatório? / What is the influence of microbiota on obesity and its inflammatory involvement?

A obesidade tem causa multifatorial que atinge atualmente mais da metade da população brasileira. Mais recentemente, a microbiota intestinal foi considerada um fator que contribui para essa condição. Os objetivos deste estudo foram revisar a influência da microbiota intestinal na obesidade e no processo inflamatório, e analisar os efeitos da utilização dos pré e probióticos. Foi realizada revisão sistemática sobre o assunto. Dos mais de 27.000 artigos, apenas 16 respeitaram os critérios de inclusão. Em conclusão, o desequilíbrio da microbiota aparece como fator favorável ao desenvolvimento da obesidade e do quadro inflamatório decorrente dela. Tanto o uso de prebióticos quanto probióticos são recursos válidos no tratamento da obesidade, porém os primeiros parecem proporcionar melhor qualidade de vida.

Obesity has a multifactorial etiological condition that involves more than half of the Brazilian population. More recently, the intestinal microbiota was considered a factor that contributes to this condition. The aims of this study were to review the intestinal microbiota influence in the obesity and in the inflammatory response, and to analyze the effects of using prebiotic and probiotic medications. A systematic review was firstly done. More than 27,000 articles were found, but only 16 contained the proper criteria. In conclusion, the microbiota imbalance seems to increase the obesity development and its inflammatory aspects. Both the use of pre and probiotics are good options in the obesity treatment, though the first ones seem to enhance bettere quality of life.

Etiology and clinical classification of constipation / 中华胃肠外科杂志

The causes of constipation are extremely complex and are still not fully clear. In addition to secondary factors such as organic diseases and drugs, constipation may also be related to genetics, diet, intestinal flora, age, gender and so on. At present, according to the etiology, chronic constipation is divided into primary constipation and secondary constipation. However, there are significant differences among current clinical guidelines in the clinical classification of primary constipation. Some guidelines classify primary constipation as slow-transit constipation (STC), outlet obstruction constipation (OOC), and mixed constipation; however, some guidelines classify primary constipation as STC, defecation disorder (DD), mixed constipation, and normal-transit constipation (NTC); what's more, some even propose types which are different from the above sub-types. There are also differences in the understanding of the relationship between functional constipation (FC) and primary constipation and the classification of irritable bowel syndrome predominant constipation (IBS-C) among various clinical guidelines. By reviewing domestic and international guidelines and relevant literature on constipation, the following conclusions are drawn: primary constipation can be divided into IBS-C and FC, and FC can be further divided into STC, OOC, and mixed constipation; primary constipation should not be confused with FC, nor should IBS-C be classified as FC.

Therapeutic effect and mechanism of Shouhui Tongbian Capsules on slow transit constipation model mice / 中国中药杂志

Shouhui Tongbian Capsules was used to explore the therapeutic effect and potential mechanism on slow transit constipation model mice induced by loperamide hydrochloride. In the experiment, loperamide hydrochloride-induced ICR mice were used as the model of slow transit constipation. Fifty ICR mice were divided into the blank group, model group and high, medium and low dose groups of Shouhui Tongbian Capsules extract(100, 200 and 400 mg·kg~(-1)). The model group and the administration groups were then modeled using loperamide hydrochloride intragastrically to obtain slow transit constipation. After successful modeling, high, medium and low doses of drugs were given to each drug group by intragastric administration. After 14 days of administration, the first defecation time, 6 h defecation grain number, 6 h defecation wet weight and dry weight, black feces discharged within 6 h and the fecal water content were measured. Intestinal tissues were taken for c-Kit and SCF immunohistochemical sections to detect the expression of c-Kit and SCF in the blank group, model group and high, medium and low dose groups of the medicinal extract of Shouhui Tongbian Capsules. The tissue changes in the intestinal wall of mice were detected by HE staining. At the same time, partial intestinal tissues were taken to test the activity of ATP synthase and isocitrate dehydrogenase in intestinal tissues of mice. RESULTS:: showed that Shouhui Tongbian Capsules effectively improved the symptoms of slow transit constipation in ICR mice and promoted intestinal movement. Shouhui Tongbian Capsules obviously shortened the time of discharging black stool for the first time, improved the intestinal propulsion rate, increased the water content and amount of feces, and improved the constipation symptoms. Mechanism study revealed that Shouhui Tongbian Capsules increased ATP synthase activity and mitochondrial isocitrate dehydrogenase activity in intestinal tissue, and up-regulated c-Kit/SCF signaling pathway to promote interstitial Cajal cells proliferation, intestinal nerve transmission, intestinal motility and transport capacity.

Paternal obesity and its transgenerational effects on gastrointestinal function in male rat offspring

The interplay between obesity and gastrointestinal (GI) motility is contradictory, and the transgenerational influence on this parameter is unknown. We aimed to evaluate the GI function in a model of paternal obesity and two subsequent generations of their male offspring. Newborn male rats were treated with monosodium glutamate (MSG) and composed the F1 generation, while control rats (CONT) received saline. At 90 days, male F1 were mated with non-obese females to obtain male offspring (F2), which later mated with non-obese females for obtaining male offspring of F3 generation. Lee Index analysis was adopted to set up the obesity groups. Alternating current biosusceptometry (ACB) technique was employed to calculate GI transit parameters: mean gastric emptying time (MGET), mean cecum arrival time (MCAT), mean small intestinal transit time (MSITT), and gastric frequency and amplitude of contractions. Glucose, insulin, and leptin levels and duodenal morphometry were measured. F1 obese rats showed a decrease in the frequency and amplitude of gastric contractions, while obese rats from the F2 generation showed accelerated MGET and delayed MCAT and MSITT. Glucose and leptin levels were increased in F1 and F2 generations. Insulin levels decreased in F1, F2, and F3 generations. Duodenal morphometry was altered in all three generations. Obesity may have paternal transgenerational transmission, and it provoked disturbances in the gastrointestinal function of three generations.

Anatomic-radiographic aspects and gastrointestinal transit time in Boa constrictor amarali Stull, 1932 (Squamata, Boidae) / [Aspectos anátomo-radiográficos e tempo de trânsito gastrointestinal em jiboia-cinzenta Boa constrictor amarali Stull, 1932 (Squamata, Boidae)]

The goal of this study was to describe the gastrointestinal transit technique in the Boa constrictor amarali. For that purpose, we obtained simple radiographic images of seven serpents, subsequently administering a 25mL/kg dose of barium sulfate and establishing a radiographic sequence at the following times: 5 minutes; 1, 2, 3, 6, 9, 24, 48, 72 and 96 hours, extending to 120 and 126 hours for one animal. The mean esophageal transit was 26.71±19.48 hours; the mean gastric filling time was 28.57±27.22 minutes and the emptying time was 60±12 hours; the mean filling time of the contrast medium in the small intestine was 3±2.16 hours and the emptying time was 97±15.65 hours. We also obtained the mean filling time of the large intestine, which was 40±11.31 hours. We found that the mean passage time of the contrast medium through the cranial gastrointestinal tract - until the complete elimination of barium sulfate from the small intestine -was 97±15.65 hours. In addition to determining the gastrointestinal transit time, the technique used allowed for the morphological identification of the alimentary canal.(AU)

O objetivo deste trabalho foi descrever a técnica de trânsito gastrointestinal em Boa constrictor amarali. Para tanto, foram obtidas radiografias simples de sete serpentes, e, subsequentemente a essas, foi administrado sulfato de bário na dose de 25mL/kg. A partir disso, foi estabelecida a sequência radiográfica nos seguintes tempos: cinco minutos; uma, duas, três, seis, nove, 24, 48, 72 e 96 horas, e em um animal estendeu-se para 120 e 126 horas. O trânsito esofágico médio foi de 26,71±19,48 horas, o tempo médio de preenchimento gástrico foi de 28,57±27,22 minutos, e o esvaziamento de 60±12 horas; a média de tempo de enchimento do meio de contraste no intestino delgado foi de 3±2,16 horas e, por fim, o esvaziamento foi de 97±15,65 horas, e ainda obteve-se o tempo médio de enchimento do intestino grosso igual a 40±11,31 horas. Desse modo, verificou-se que a média do tempo de passagem do contraste pelo trato gastrointestinal cranial - até a completa eliminação do sulfato de bário do intestino delgado - foi de 97±15,65 horas. Além da determinação do tempo de trânsito gastrointestinal, a técnica empregada permitiu a identificação morfológica do canal alimentar.(AU)

The real impact of colonic transit time and anorectal manometry in the diagnosis of adult patients with chronic constipation / O real impacto do tempo de trânsito cólico e da manometria anorretal no diagnóstico de pacientes adultos com constipação crônica

Abstract Introduction: Anorectal physiology tests are indicated for patients who have refractory symptoms of constipation, but the best sequence of investigation remains controversial. Objective: To evaluate the influence of colonic transit time and anorectal manometry in the diagnosis of chronic constipation in adults. Method: This was a study of adult patients with constipation at a private clinic in a city in southern Brazil, from January 1, 2009 to December 31, 2018. Those who showed warning signs were referred for colonoscopy and those with any anatomical alterations were excluded. The patients received 10 g of psyllium and those who remained symptomatic after three weeks were referred for functional assessment with colonic transit time (CTT). Those who presented outlet obstruction in the colonic transit time were referred to anorectal manometry. Results: Of the 889 adult patients surveyed, 227 were included. Of the 216 who completed the study, 167 responded to primary treatment. Forty-nine underwent CTT. In these, 16 had normal colonic transit time and 33 were altered. In those with altered colonic transit time, eight had a pattern of colonic inertia and 25 had an obstruction pattern. The 25 patients with an outlet obstruction pattern underwent anorectal manometry. Eighteen had signs of paradoxical contracture of the puborectal muscle (PPRC) and seven did not. Conclusion: This study concluded that anorectal physiology exams contribute to the diagnosis of constipation, often changing the behavior. These exams should be performed whenever the patient does not respond to hygienic changes and fiber replacement.

Resumo Introdução: Os exames de fisiologia anorretal estão indicados nos pacientes que mantém sintomas refratários de constipação, porém uma sequência desejada de investigação permanece contraditória. Objetivo: Avaliar a influência do tempo de trânsito colônico e da manometria anorretal no diagnóstico da constipação crônica de adultos. Método: Estudamos os pacientes adultos de uma clínica privada em uma cidade do sul do Brasil, no período de 01 de Janeiro de 2009 a 31 de Dezembro de 2018 apresentando constipação. Aqueles que apresentassem sinais de alerta, eram encaminhados a colonoscopia e com qualquer alteração anatômica eram excluídos. Foram prescritos 10 g de Psyllium e aqueles que permaneceram sintomáticos após três semanas foram encaminhados à avaliação funcional com tempo de trânsito colônico (TTC). Os que apresentavam obstrução de saída ao tempo de trânsito colônico foram encaminhados a manometria anorretal. Resultados: Dos 889 pacientes adultos levantados, 227 foram incluídos. Dos 216 que concluíram o estudo, 167 responderam ao tratamento primário. Quarenta e nove realizaram TTC. Nestes, 16 tiveram tempo de trânsito colônico normal e 33 alterado. Naqueles com tempo de trânsito colônico alterado: oito tinham padrão de inércia colônica e 25, padrão de obstrução de saída. Os 25 pacientes com padrão de obstrução de saída foram submetidos à manometria anorretal. Dezoito tinham sinais de Contratura Paradoxal do músculo Puborretal (CPPR) e sete não. Conclusão: Concluímos que os exames de fisiologia anorretal contribuem para o diagnóstico da constipação, muitas vezes alterando a conduta. Estes exames devem ser realizados sempre que o paciente não responder as alterações higienodietéticas e a reposição de fibras.

Structural bases of gastrointestinal motility changes in parkinson's disease: study in rats / Bases estruturais das alterações da motilidade gastrintestinal na doença de parkinson: estudo em ratos

ABSTRACT Background: Gastrointestinal disorders are frequently reported in patients with Parkinson's disease whose disorders reduce the absorption of nutrients and drugs, worsening the clinical condition of patients. However, the mechanisms involved in modifying gastrointestinal pathophysiology have not yet been fully explained. Aim: To evaluate its effects on gastrointestinal motility and the involvement of the vagal and splanchnic pathways. Methods: Male Wistar rats (250-300 g, n = 84) were used and divided into two groups. Group I (6-OHDA) received an intrastriatal injection of 6-hydroxydopamine (21 µg/animal). Group II (control) received a saline solution (NaCl, 0.9%) under the same conditions. The study of gastric emptying, intestinal transit, gastric compliance and operations (vagotomy and splanchnotomy) were performed 14 days after inducing neurodegeneration. Test meal (phenol red 5% glucose) was used to assess the rate of gastric emptying and intestinal transit. Results: Parkinson's disease delayed gastric emptying and intestinal transit at all time periods studied; however, changes in gastric compliance were not observed. The delay in gastric emptying was reversed by pretreatment with vagotomy and splanchnotomy+celiac gangliectomy, thus suggesting the involvement of such pathways in the observed motor disorders. Conclusion: Parkinson's disease compromises gastric emptying, as well as intestinal transit, but does not alter gastric compliance. The delay in gastric emptying was reversed by truncal vagotomy, splanchnotomy and celiac ganglionectomy, suggesting the involvement of such pathways in delaying gastric emptying.

RESUMO Racional: Distúrbios gastrintestinais são frequentemente relatados em pacientes com doença de Parkinson cujos distúrbios reduzem a absorção de nutrientes e fármacos, agravando o quadro clínico dos pacientes. No entanto, os mecanismos envolvidos na alteração da fisiopatologia gastrintestinal ainda não foram totalmente elucidados. Objetivo: Avaliar os seus efeitos sobre a motilidade gastrintestinal e o envolvimento das vias vagal e esplâncnica. Métodos: Ratos Wistar machos (250-300 g, n=84) foram utilizados e divididos em dois grupos. O grupo I (6-OHDA) recebeu injeção intraestriatal de 6-hidroxidopamina (21 µg/animal). O grupo II (controle) recebeu solução salina (NaCl, 0,9%) nas mesmas condições. O estudo do esvaziamento gástrico, trânsito intestinal, complacência gástrica e operações (vagotomia e esplancnotomia) foram realizadas 14 dias após a indução da neurodegeneração. Refeição teste (vermelho de fenol+glicose 5%) foi utilizada para avaliar a taxa de esvaziamento gástrico e o trânsito intestinal. Resultados: A doença de Parkinson retardou o esvaziamento gástrico e o trânsito intestinal em todos os tempos estudados; porém, alterações da complacência gástrica não foram observadas. O retardo do esvaziamento gástrico foi revertido por pré-tratamento com vagotomia e esplancnotomia+gangliectomia celíaca, sugerindo assim, o envolvimento de tais vias nos distúrbios motores observados. Conclusão: A doença de Parkinson compromete o esvaziamento gástrico, bem como o trânsito intestinal, mas não altera a complacência gástrica. O retardo do esvaziamento gástrico foi revertido pela vagotomia troncular, esplancnotomia e gangliectomia celíaca, sugerindo o envolvimento de tais vias no retardo do esvaziamento gástrico.

Sericin as treatment of obesity: morphophysiological effects in obese mice fed with high-fat diet / Sericina como tratamento da obesidade: efeitos morfofisiológicos de camundongos obesos por dieta hiperlipídica

ABSTRACT Objective To investigate the effects of sericin extracted from silkworm Bombyx mori cocoon on morphophysiological parameters in mice with obesity induced by high-fat diet. Methods Male C57Bl6 mice aged 9 weeks were allocated to one of two groups - Control and Obese, and fed a standard or high-fat diet for 10 weeks, respectively. Mice were then further subdivided into four groups with seven mice each, as follows: Control, Control-Sericin, Obese, and Obese-Sericin. The standard or high fat diet was given for 4 more weeks; sericin (1,000mg/kg body weight) was given orally to mice in the Control-Sericin and Obese-Sericin Groups during this period. Weight gain, food intake, fecal weight, fecal lipid content, gut motility and glucose tolerance were monitored. At the end of experimental period, plasma was collected for biochemical analysis. Samples of white adipose tissue, liver and jejunum were collected and processed for light microscopy analysis; liver fragments were used for lipid content determination. Results Obese mice experienced significantly greater weight gain and fat accumulation and had higher total cholesterol and glucose levels compared to controls. Retroperitoneal and periepididymal adipocyte hypertrophy, development of hepatic steatosis, increased cholesterol and triglyceride levels and morphometric changes in the jejunal wall were observed. Conclusion Physiological changes induced by obesity were not fully reverted by sericin; however, sericin treatment restored jejunal morphometry and increased lipid excretion in feces in obese mice, suggesting potential anti-obesity effects.

RESUMO Objetivo Investigar os efeitos da sericina extraída de casulos de Bombyx mori na morfofisiologia de camundongos com obesidade induzida por dieta hiperlipídica. Métodos Camundongos machos C57Bl6, com 9 semanas de idade, foram distribuídos em Grupos Controle e Obeso, que receberam ração padrão para roedores ou dieta hiperlipídica por 10 semanas, respectivamente. Posteriormente, os animais foram redistribuídos em quatro grupos, com sete animais cada: Controle, Controle-Sericina, Obeso e Obeso-Sericina. Os animais permaneceram recebendo ração padrão ou hiperlipídica por 4 semanas, período no qual a sericina foi administrada oralmente na dose de 1.000mg/kg de massa corporal aos Grupos Controle-Sericina e Obeso-Sericina. Parâmetros fisiológicos, como ganho de peso, consumo alimentar, peso das fezes em análise de lipídios fecais, motilidade intestinal e tolerância à glicose foram monitorados. Ao término do experimento, o plasma foi coletado para dosagens bioquímicas e fragmentos de tecido adiposo branco; fígado e jejuno foram processados para análises histológicas, e amostras hepáticas foram usadas para determinação lipídica. Resultados Camundongos obesos apresentaram ganho de peso e acúmulo de gordura significativamente maior que os controles, aumento do colesterol total e glicemia. Houve hipertrofia dos adipócitos retroperitoneais e periepididimais, instalação de esteatose e aumento do colesterol e triglicerídeos hepáticos, bem como alteração morfométrica da parede jejunal. Conclusão O tratamento com sericina não reverteu todas as alterações fisiológicas promovidas pela obesidade, mas restaurou a morfometria jejunal e aumentou a quantidade de lipídios eliminados nas fezes dos camundongos obesos, apresentando-se como potencial tratamento para a obesidade.

Effects of anti-TNF-α in experimental diversion colitis

Abstract Purpose: To evaluate the effects of infliximab on the inflammation of the colonic mucosa devoid from fecal stream. Methods: Twenty-four rats were submitted to a Hartmann's procedure. They remained for 12 weeks with the fecal derivation to development of diversion colitis on excluded colorectal stump. After this period, they were divided into 3 groups: one group received intervention with saline (2.0 mL / week), other group infliximab at doses of 5 mg/kg/week and the other 10 mg/kg/week for five consecutively weeks. Concluded the intervention period, the animals were euthanized to remove colon segments with and without fecal stream. Colitis was diagnosed by histological analysis and the degree of inflammation by validated score. The neutrophilic infiltrate was evaluated by tissue expression of myeloperoxidase identified by immunohistochemical. The tissue content of myeloperoxidase was measured by computer-assisted image analysis. Results: The inflammatory score was high in colonic segments without fecal stream. The intervention with infliximab reduced the inflammatory score in excluded colonic segments. The content of myeloperoxidase was reduced in colonic segments of animals treated with infliximab mainly in high concentrations. Conclusion: Intervention with infliximab reduced the inflammation and the neutrophil infiltrate in colonic segments devoid of the fecal stream.

Elevated Intrabolus Pressure Predicts Abnormal Timed Barium Esophagram in Esophagogastric Junction Outflow Obstruction

BACKGROUND/AIMS: Timed barium esophagram (TBE) is used the classification of esophageal motility disorders and assessing esophageal function. Currently, there are no published studies examining the relationship between high-resolution manometry and TBE in patients with esophagogastric junction outflow obstruction (EGJOO). This study seeks to evaluate this relationship and identify manometric variables that may indicate further evaluation using TBE. METHODS: Retrospective review of medical records identified patients with a diagnosis of EGJOO per the Chicago classification version 3.0. TBE was performed using standard protocol. Patients were divided into 2 groups based on complete emptying or persistence of standing barium column at 5 minutes. RESULTS: Eleven patients were identified with EGJOO who underwent both high-resolution manometry and TBE within 3 months. Five patients had no standing barium column at 5 minutes, while 6 patients had a persistent barium column. Mean age of each group was 54.0 years and 57.8 years, respectively. Patients with abnormal TBE were found to have significantly elevated intrabolus pressure (IBP) compared with patients who had a normal TBE. CONCLUSIONS: In our study, we found significant differences in IBP between these patient groups. These findings suggest that patients with EGJOO and elevated IBP may prompt further clinical evaluation with TBE in order to clarify clinical diagnosis and guide therapeutic intervention.

Effects of Naloxegol on Gastrointestinal Transit and Colonic Fecal Volume in Healthy Participants Receiving Oxycodone

BACKGROUND/AIMS: Opioids cause gastrointestinal (GI) dysmotility, decrease gut secretion, and affect gut sphincters. Symptoms of opioid-induced bowel dysfunction may be alleviated by peripherally acting opioid antagonists like naloxegol, but detailed knowledge on GI effects of this drug is lacking. We hypothesized that naloxegol, compared to placebo, would reduce GI transit time and colonic fecal volume in opioid-treated healthy participants. METHODS: We conducted a randomized, double-blinded, single-center, 2-way cross-over study in 24 healthy males, randomized to a 6 day treatment period of oxycodone (15 mg twice a day) co-administered with either naloxegol (25 mg once a day) or matching placebo. Participants swallowed an electromagnetic capsule which determined GI transit times. Colonic fecal volume was quantified with magnetic resonance imaging both pre-treatment and post-treatment. RESULTS: Naloxegol reduced total GI transit time by 21% (56 hours vs 71 hours, P = 0.02) and colonic transit time by 23% (45 hours vs 59 hours, P < 0.01), compared to placebo. However, no difference in colonic fecal volume was found (818 mL vs 884 mL, P = 0.20). CONCLUSIONS: Short-term administration of naloxegol in healthy participants reverses the retardation of total GI and colonic transit induced by oxycodone. This supports the use of naloxegol in the treatment of GI side effects to opioid treatment, and add knowledge to the current understanding of mechanisms behind peripherally-acting opioid antagonists.

Enemas with mesalazine increase the tissue contents of mucins in the colonic mucosa devoid of fecal stream

Abstract Purpose: To evaluate the inflammatory reaction and measure the content of mucins, in the colonic mucosa without fecal stream submit to intervention with mesalazine. Methods: Twenty-four rats were submitted to a left colostomy and a distal mucous fistula and divided into two groups according to euthanasia to be performed two or four weeks. Each group was divided into two subgroups according daily application of enemas containing saline or mesalazine at 1.0 g/kg/day. Colitis was diagnosed by histological analysis and the inflammatory reaction by validated score. Acidic mucins and neutral mucins were determined with the alcian-blue and periodic acid of Schiff techniques, respectively. Sulfomucin and sialomucin were identified by high iron diamine-alcian blue technique. The tissue contents of mucins were quantified by computer-assisted image analysis. Mann-Whitney test was used to analyze the results establishing the level of significance of 5%. Results: Enemas with mesalazine in colonic segments without fecal stream decreased the inflammation score and increased the tissue content of all subtypes of mucins. The increase of tissue content of neutral, acid and sulfomucin was related to the time of intervention. Conclusion: Mesalazine enemas reduce the inflammatory process and preserve the content of mucins in colonic mucosa devoid of fecal stream.

Efecto del endospermo de semilla de tara y polvo de hojas de Agave americana en el peso corporal y velocidad de tránsito intestinal en ratas / Effects of the endosperm of tara seeds and powder of Agave Americana leaves on body weight and intestinal transit time in holtzman rats

RESUMEN Objetivos. Evaluar el efecto del endospermo de semilla de tara (EST) y polvo de hojas del Agave americana (HAA) sobre el peso corporal y velocidad de tránsito intestinal en ratas Holtzman. Materiales y métodos Veinticinco ratas machos Holtzman distribuidas en cinco grupos y alojadas en jaulas individuales, fueron alimentadas durante 21 días con uno de los siguientes tratamientos: T1, dieta con 6% de alfa celulosa (control); T2, dieta con 6% de EST; T3, dieta con 6% de HAA; T4, dieta con 10% de EST y T5, dieta con 10% de HAA. Se registraron el consumo de alimento, ganancia de peso corporal, digestibilidad aparente de la grasa, características de las heces (contenido de grasa, peso, humedad, volumen y pH) y tiempo de tránsito intestinal. Se realizaron análisis de varianza (ANOVA) de una vía y a través de la comparación múltiple de medias de Tukey. Resultados Dietas con 6% y 10% del EST exhibieron una reducción en el consumo de alimento, digestibilidad aparente de la grasa y pH fecal, cuyos resultados tuvieron efectos en la reducción de la ganancia del peso corporal de 37,0% (p=0,008) y 50,9% (p=0,001) comparados con la dieta control. Dieta con 10% del polvo de HAA redujo el tiempo de tránsito intestinal de 642 min (control) a 532 min (p=0,242). Conclusiones Dietas que contienen EST regulan la ganancia del peso corporal; en cambio, dieta con polvo de HAA, no tuvo efectos sobre la velocidad de tránsito intestinal en ratas.

ABSTRACT Objective To evaluate the effects of endosperm of tara seeds (ETS) and powder of Agave americana leaves (AAL) on body weight and intestinal transit time in Holtzman rats. Materials and Methods Twenty-five male Holtzman rats, individually caged, and distributed into five groups were fed for 21 days with one of the following treatments: T1, diet with 6% alpha cellulose (Control); T2, diet with 6% ETS; T3, diet with 6% AAL; T4, diet with 10% ETS; and T5, Diet with 10% AAL. Feed intake, body weight gain, apparent digestibility of fat, characteristics of feces (fat content, weight, moisture, volume, and pH) and intestinal transit time were recorded. One-way analyses of variance (ANOVA) were performed, as well as Tukey's multiple means comparison. Results Diets with 6% and 10% of ETS resulted in a reduction of feed intake, apparent digestibility of fat, and fecal pH, and said results had an effect in the reduction of body weight gain of 37.0% (p=0.008) and 50.9% (0.001), compared with the control diet. The diet with 10% of AAL powder reduced the intestinal transit time from 642 min (control) to 532 min (p=0.242). Conclusions Diets containing EST regulated body weight gain, while the diet with AAL powder had no effects on the intestinal transit time in rats.

Progress in the treatment of surgical procedures for slow transit constipation / 中华胃肠外科杂志

Slow transit constipation (STC) is the most common type of chronic constipation, and surgical treatment is one of the most important means for the treatment of slow transit constipation. With the introduction of the concept of STC and the normalization of STC treatment, development of surgical treatment in slow transit constipation is continuous, and the innovation of the operation method in slow transit constipation is continuous as well from partial colectomy, total colectomy (including ileorectal anastomosis, anorectal anastomosis and ileum bag anal canal anastomosis) to subtotal colectomy (including ileosigmoid colon anastomosis, isoperistaltic cecum rectal anastomosis and antiperistaltic cecum rectal anastomosis). Among these procedures, total colectomy ileorectal anastomosis is the ideal surgical procedure for the treatment of STC. Recent studies revealed that subtotal colectomy cecum rectal anastomosis could also achieve good efficacy. In addition, the other procedures for the treatment of STC include ileostomy, anterograde colonic lavage and colon exclusion, but it is necessary to strictly grasp the indications. With the development of minimally invasive technology, the application of laparoscopic technology in STC has been emphasized gradually. In general, the operation method has experienced from simple to complex and individual choice; from single surgical approach to multiple surgical methods; from abdominal open surgery to laparoscopic minimally invasive surgery. Relieving constipation symptoms and reducing the incidence of complications is the goal of surgical treatment that has always been the pursuit of STC surgery. The surgical method with good efficacy, small trauma, quick recovery and less complications must be designed to meet the individualized needs of patients with different constipations. In this paper, the efficacy and progress of surgical treatment of slow transit constipation from the generation and development are reviewed.

Tempo de trânsito oral na demência de Alzheimer / Oral transit time in Alzheimer's disease

RESUMO Objetivo Avaliar o tempo de trânsito oral de alimento na consistência pudim, nos diferentes estágios da demência de Alzheimer. Métodos Estudo de caráter descritivo e observacional do tipo transversal, com uma amostra de 34 idosos com idade entre 65 e 98 anos, com demência de Alzheimer em diferentes estágios. Os participantes foram observados por avaliação de videofluoroscopia da deglutição, enquanto ingeriam alimento na consistência pudim, usando o programa de cronometragem Kinovea. Os dados foram analisados estatisticamente, em nível de significância de 5%. Resultados Os participantes com o Clinical Dementia Rating CDR 3 apresentaram maior tempo de trânsito oral, quando comparados àqueles com CDR 1, média de 3,09s (desvio padrão = 0,91) e 1,17s (desvio padrão = 1,10), respectivamente. Participantes na faixa etária de 90a 100 anos apresentaram maior tempo de trânsito oral do que os mais jovens, entre 60 e 79 anos, média de 3,90s e 1,28s. Conclusão Indivíduos com demência e idade avançadas apresentam tempo de trânsito oral aumentado para alimento na consistência pudim, devendo ser alvo de atenção de familiares e cuidadores.

ABSTRACT Purpose Evaluate oral transit time (OTT) with pudding consistency at the different stages of Alzheimer's disease (AD). Methods Descriptive, cross-sectional, observational study conducted with a sample of 34 elderly aged 65-98 years, with AD at different stages. Participants were observed using videofluoroscopy of swallowing while ingesting pudding consistency, using the Kinovea timing program. Data were statistically analyzed at 5% significance level. Results Participants with Clinical Dementia Rating - CDR 3 presented longer OTT compared with those with CDR 1, with means of 3.09 s (SD = 0.91) and 1.17 s (SD = 1.10), respectively. Individuals aged 90-100 years presented longer OTT than those aged 60-79 years, means of 3.90 s and 1.28 s, respectively. Conclusion Individuals with dementia and advanced aged present longer OTT for pudding consistency and should receive special attention from family members and caregivers.

Fatores associados a não reconstrução do trânsito intestinal em pacientes com câncer retal submetidos à ressecção anterior do reto e ileostomia de proteção / Factors preventing restoration of bowel continuity in patients with rectal cancer submitted to anterior rectal resection and protective ileostomy

RESUMO Objetivo: avaliar os fatores associados ao não fechamento de ileostomia protetora após ressecção anterior do reto com excisão total do mesorreto por câncer retal, a morbidade associada ao fechamento destas ileostomias e a taxa de estomia permanente em pacientes com adenocarcinoma retal. Métodos: estudo retrospectivo de 174 pacientes consecutivos com diagnóstico de tumores retais, dos quais 92 foram submetidos à ressecção anterior do reto com intenção curativa, anastomose coloanal ou colorretal e ileostomia de proteção. Foi realizada análise multivariada visando a determinar os fatores associados à permanência definitiva da estomia, assim como o estudo da morbidade nos que se submeteram à reconstrução do trânsito. Resultados: no período de seguimento de 84 meses, 54 dos 92 pacientes avaliados (58,7%) tiveram a ileostomia fechada e 38 (41,3%) permaneceram com a estomia. Entre os 62 pacientes que tiveram a ileostomia fechada, 11 (17,7%) apresentaram algum tipo de complicação pós-operatória: três com deiscência de anastomose ileal, cinco com obstrução intestinal, dois com infecção de ferida operatória e um com pneumonia. Oito destes pacientes necessitaram de um novo estoma. Conclusão: de acordo com a análise multivariada, os fatores associados à permanência da estomia foram fístula de anastomose, presença de metástases e fechamento da ileostomia durante quimioterapia.

ABSTRACT Objective: to evaluate the factors associated with non-closure of protective ileostomy after anterior resection of the rectum with total mesorectum excision for rectal cancer, the morbidity associated with the closure of ileostomies and the rate of permanent ileostomy in patients with rectal adenocarcinoma. Methods: we conducted a retrospective study with 174 consecutive patients diagnosed with rectal tumors, of whom 92 underwent anterior resection of the rectum with coloanal or colorectal anastomosis and protective ileostomy, with curative intent. We carried out a multivariate analysis to determine the factors associated with definite permanence of the stoma, as well as studied the morbidity of patients who underwent bowel continuity restoration. Results: In the 84-month follow-up period, 54 of the 92 patients evaluated (58.7%) had the ileostomy closed and 38 (41.3%) remained with the stoma. Among the 62 patients who had the ileostomy closed, 11 (17.7%) presented some type of postoperative complication: three had ileal anastomosis dehiscence, five had intestinal obstruction, two had surgical wound infection, and one, pneumonia. Eight of these patients required a new stoma. Conclusion: according to the multivariate analysis, the factors associated with stoma permanence were anastomotic fistula, presence of metastases and closure of the ileostomy during chemotherapy.

Ethacrynic acid decreases expression of proinflammatory intestinal wall cytokines and ameliorates gastrointestinal stasis in murine postoperative ileus

OBJECTIVES: Several compounds characterized by an olefin linkage conjugated to a carbonyl group have anti-inflammatory properties. The diuretic ethacrynic acid (EA) is a compound of this type. Herein, we tested the hypothesis that ethacrynic acid can modulate the development of ileus after bowel manipulation. METHODS: Groups (n=9) of male C57Bl/6 mice underwent surgical manipulation of the small intestine using a pair of cotton-tipped applicators (MAN). Control animals (CONT) did not undergo any surgical intervention or receive treatment. MAN mice were pre- and post-treated with four intraperitoneal doses of phosphate buffered saline (PBS), EA1 (1mg/kg per dose), or EA10 (10mg/kg per dose). Gastrointestinal transit of non-absorbable FITC-labeled dextran was assessed by gavaging the mice with the tracer 24h after operation and assessing FD70 concentration 120 min later in the bowel contents from the stomach, 10 equally long segments of small intestine, cecum, and two equally long segments of colon. The geometric center for the tracer was calculated for each animal. Expression of interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS) transcripts in the ileal muscularis propria was assessed using semiquantitative reverse transcriptase-polymerase chain reaction. RESULTS: In control animals, the mean (±SE) geometric center for the transit marker was 9.89±0.47, whereas it was 4.59±0.59 for PBS-treated animals (p<0.05 vs CONT). The geometric center for pre- post treatment with low (1mg/kg) and high (10mg/kg) doses of ethacrynic acid were 7.23±0.97 and 5.15±0.57, respectively. Compared to PBS, treatment with ethacrynic acid (1mg/kg) significantly decreased manipulation-induced IL-6 and iNOS mRNA expression in the wall of the small bowel. CONCLUSIONS: Pre- and post-treatment with ethacrynic acid ameliorates ileus and modulates inflammation in the gut wall induced by bowel manipulation.

Effect of bisacodyl on rats with slow transit constipation

The effect of bisacodyl on the treatment of rats with slow transit constipation (STC) was studied. Forty-five female Wister rats were divided into control group, STC group, and STC bisacodyl group. The immunohistochemical method was used to determine interstitial cells of Cajal (ICC) and the expression of c-Kit protein. Body mass and the number of defecations were significantly decreased in the STC group compared with the control group on the 100th day after diphenoxylate administration, while dry weight of feces was significantly increased and the intestinal transit time was prolonged. There were significant differences in the number of defecations, dry weight of feces, and intestinal transit time among the three groups. The number of defecations was higher, dry weight of feces was lower, and intestinal transit time was shorter in the STC bisacodyl group compared to the STC group. In addition, ICC basement membrane dissolution occurred in the colon wall of the STC group. The connection between ICC and surrounding cells was destroyed, and the nucleus shrunken to different degrees. Moreover, c-Kit expression in the STC group was significantly lower than the control group. The connection between ICC and surrounding cells in the STC bisacodyl group was significantly stronger than the STC group, and the number of ICC and the expression of c-Kit were increased. Bisacodyl could reduce the severity of STC in rats by increasing the number of ICC and the expression of c-Kit.

Bipartición de tránsito intestinal, la nueva era de la cirugía metabólica para la diabetes mellitus de tipo 2 / Intestinal transit bipartition, the new era in metabolic surgery for type 2 diabetes

Antecedentes. La diabetes mellitus de tipo 2 es el principal reto de salud pública que enfrentamos actualmente, constituye la primera causa de discapacidad y es o está asociada a las principales causas de muerte en nuestro país. En Ciudad de México, se reportó que más del 79 % de los pacientes diabéticos no tienen cifras óptimas de HbA1c (<6,5 %), mientras que el 47 % presentan descontrol importante (HbA1c >9 %). La cirugía metabólica es el mejor tratamiento en términos de remisión, sin embargo, los mecanismos involucrados no son los tradicionalmente considerados. Objetivo. Ofrecer actualización acerca de los mecanismos involucrados en la remisión de la diabetes mellitus de tipo 2 después de la cirugía metabólica. Metodos. Se hizo una revisión bibliográfica utilizando las palabras clave en términos MeSH; hasta el 1° de junio del 2018, se encontraron 83 artículos de referencia considerados como pertinentes. Resultados. La remisión de la diabetes mellitus de tipo 2 lograda por procedimientos quirúrgicos, depende de complejas interacciones entre la microbiota, los ácidos biliares y el epitelio intestinal, más que de procesos malabsortivos o restrictivos. La bipartición de tránsito intestinal es una opción quirúrgica basada en los principios fisiológicos responsables en la remisión de la diabetes, y es la más sencilla y segura para el manejo de la diabetes mellitus. Conclusiones. La cirugía metabólica ofrece mejores tasas de remisión y control de complicaciones de la diabetes tipo 2 al modificar la secreción de enterohormonas, la concentración e interacciones de los ácidos biliares y al modificar la microbiota

Background: Diabetes mellitus type 2 (DM2) is a major public health challenge that we face today; it is the first cause of disability and is associated with the main causes of death in our country. In Mexico City, it was reported that more than 79% of diabetic patients did not have optimal levels of HbA1c (<6.5%), while 47% are not properly controlled (HbA1c> 9%). Metabolic surgery is the best treatment option for DM2, yet the presumed involved mechanisms are not traditionally considered. Objective: To provide an update on the mechanisms involved in the remission of DM2 following metabolic surgery. Methods: Narrative review of the literature, using MeSH terms, until June 1, 2018, encountering 83 articles considered pertinent. Methods: Narrative review of the literature, using MeSH terms, until June 1, 2018, encountering 83 articles considered pertinent. Results: DM2 remission after surgery depends on complex interactions between the microbiota, biliary acids and the intestinal epithelium, more so than of malabsortion or restrictive processes. Bipartition of the intestinal transit constitutes a surgical option based on the physiologic principles responsible of the remission of diabetes, and it is a simple and most secure procedure for the management of diabetes. Mechanisms include restoration/ enhancement of incretin secretion; as well as an improvement of bile acid concentration and microbiome manipulation, rather than the commonly accepted restriction and malabsorption. Intestinal transit bipartition is a novel and simple procedure that complies with the actual involved mechanisms, with comparable results in terms of safety and efficacy with the more complex and demanding techniques, such as the gastric bypass. Conclusions: Metabolic surgery is the best treatment for DM2 in terms of remission and prevention of complications, modifying the secretion of enterohormones, the concentration of biliary acids, and the modification of the microbiota

Desenvolvimento de comprimidos de liberação prolongada de nimesulida contendo ferrita para avaliação do trânsito gastrintestinal por meio de técnica biomagnética / Development of prolonged release tablets of nimesulide containing ferrite for evaluation of gastrointestinal transit by means of biomagnetic technique

As Formas Farmacêuticas de Liberação Prolongada (FFLP) têm sido uma alternativa eficaz na terapia, pois proporcionam maior adesão do paciente ao tratamento em função da redução da frequência de dosagem ao longo do dia, sendo sua principal característica, a modulação da liberação/dissolução do fármaco. Entretanto, esta etapa pode ser influenciada por diferentes fatores, dentre eles: os físico-químicos relacionados ao fármaco; os farmacêuticos, principalmente relacionados aos excipientes empregados e às técnicas de obtenção da forma farmacêutica (FF) e os fisiológicos do trato gastrintestinal (TGI), como por exemplo, o pH dos líquidos do TGI, o tempo de esvaziamento gástrico, a motilidade intestinal, entre outros. Desse modo, a avaliação do trânsito da FF no TGI, após a sua administração, permite uma melhor compreensão dos fatores que podem afetar as etapas de liberação/dissolução do fármaco in vivo. Dentre as técnicas empregadas com esse objetivo, destacam-se: a cintilografia e os métodos biomagnéticos. A Biosusceptometria de Corrente Alternada (BAC) é um método biomagnético que tem se mostrado promissor para este tipo de estudo, por ser não invasivo, portátil, livre de radiação ionizante, e por apresentar acurácia e versatilidade. Diante do exposto, o presente trabalho teve como objetivos, desenvolver e caracterizar sob o aspecto biofarmacotécnico in vitro, um sistema de liberação prolongada contendo nimesulida (fármaco-modelo) e marcador magnético (ferrita), visando obtenção de ferramenta para avaliação do trânsito gastrintestinal por meio de técnica biomagnética. Para isto foram desenvolvidas quatro formulações de comprimidos de liberação prolongada contendo nimesulida, ferrita e diferentes concentrações de hidroxipropilmetilcelulose (HPMC): NF1 (30% HPMC); NF2 (23% HPMC); NF3 (17% HPMC) e NF4 (10% HPMC). Essas foram avaliadas quanto ao comportamento de dissolução por meio de ensaios com aparato 4 e avaliação da cinética e da eficiência de dissolução (ED%). Posteriormente, estudos biomagnéticos, in vitro e in vivo, foram conduzidos com emprego da técnica de BAC para a formulação selecionada. Os resultados obtidos mostraram que as 04 formulações desenvolvidas apresentaram porcentagens de dissolução distintas em função das diferentes concentrações de HPMC (NF1 = 13,2%; NF2 = 40,1%; NF3 = 72,5% e NF4 = 91,5%). A formulação NF4, com menor concentração de HPMC, foi escolhida para os estudos por meio de BAC em função dos resultados de ED% (54,3%) e por apresentar comportamento mais próximo de uma formulação de liberação prolongada. Em relação aos resultados de BAC in vitro, destaca-se que a formulação NF4 (10%HPMC) apresentou aumento de área magnética de forma independente do pH do meio, sugerindo que a hidratação/intumescimento da HPMC independe do pH. Em relação à avaliação do trânsito intestinal (estudo in vivo) foram obtidos os seguintes dados: Tempo médio de Residência Gástrica (TTR) - 89 minutos; Tempo médio do Trânsito Orocecal (TTO) - 313 minutos e Tempo médio do Trânsito Intestinal (TTI) - 224 minutos. Os dados de BAC in vivo permitiram observar que o aumento de área magnética atingiu um platô em cerca de 80 minutos após a administração da formulação NF4. A comparação dos dados de BAC in vitro e BAC in vivo, relacionados ao trânsito gastrintestinal, indica que a formulação NF4, após apresentar o ápice de intumescimento, foi capaz de manter sua estrutura permanente ao longo do TGI, favorecendo assim a liberação modulada do fármaco. Os resultados obtidos demonstraram que a formulação desenvolvida foi eficiente para avaliar e caracterizar o trânsito no TGI por meio da técnica de BAC e também permitiram uma estimativa do comportamento do fármaco em relação a solubilidade em cada porção do TGI, proporcionando assim uma ferramenta adequada para avaliação do trânsito do TGI e desenvolvimento de FFLP

Extended Release (ER) dosage forms have been an effective alternative in therapy, since they provide greater patient adherence to treatment as a function of the reduction of the frequency of dosing throughout the day, its main characteristic being the release / dissolution modulation of the drug. However, this stage can be influenced by different factors, among them: the physical and chemical related to the drug; the pharmacists, mainly related to the excipients employed and the techniques of obtaining the form dosage and the physiological ones of the gastrointestinal tract (GI tract), as for example, the pH of the liquid of the GI tract, gastric emptying time, intestinal motility, among others. Thus, assessment of dosage forms transit in GI tract after its administration allows a better understanding of the factors that may affect the drug release / dissolution steps in vivo. Among the techniques used for this purpose, the following stand out: scintigraphy and biomagnetic methods. Alternating Current Biosensiometry (ACB) is a biomagnetic method that has shown promise for this type of study, since it is non-invasive, portable, free of ionizing radiation, and because of its accuracy and versatility. In view of the above, the aim of this work was to develop and characterize a sustained release system containing nimesulide (study drug) and magnetic marker (ferrite) under the in vitro biopharmaceutical aspect, aiming to obtain a tool to evaluate the GI tract transit through means of biomagnetic technique. For this, four formulations of extended release tablets containing nimesulide, ferrite and different concentrations of hydroxypropylmethylcellulose (HPMC): NF1 (30% HPMC) were developed; NF2 (23% HPMC); NF3 (17% HPMC) and NF4 (10% HPMC). These were evaluated for dissolution behavior by apparatus 4, assays and kinetics and dissolution efficiency (ED%). Subsequently, biomagnetic studies, in vitro and in vivo, were conducted using the ACB technique for the selected formulation. The results showed that the formulations developed showed different percentages of dissolution as a function of the different concentrations of HPMC (NF1 = 13.2%, NF2 = 40.1%, NF3 = 72.5% and NF4 = 91.5%). The NF4 formulation, with a lower concentration of HPMC, was chosen for the ACB studies as a function of ED% results (54,3%) and because of the behavior of a sustained release formulation. In relation to the in vitro ACB results, the NF4 formulation (10% HPMC) showed an increase in magnetic area independently of the pH of the medium, suggesting that the HPMC hydration / swelling is independent of pH. In relation to intestinal transit evaluation (in vivo study) the following data were obtained: Mean Time of Gastric Residency (TTR) - 89 minutes; Mean Time of Orocecal Transit (OCTT) - 313 minutes and Mean Time of lntestinal Transit (TTI) - 224 minutes. ACB data in vivo showed that the increase in magnetic area reached a plateau in about 80 minutes after administration of the NF4 formulation. Comparison of in vitro ACB and ACB data in vivo, related to gastrointestinal transit, indicates that the NF4 formulation, after showing the swelling apex, was able to maintain its permanent structure throughout the GI tract, thus favoring the modulated release of the drug. The obtained results demonstrated that the developed formulation was efficient to evaluate and characterize the transit in the GI tract by means of the ACB technique and allowed a prediction of the behavior of the drug in relation to the solubility in each portion of the GI tract, thus providing a suitable tool for evaluation of the GI tract transit and the development of sustained release formulation