Nandrolone decanoate impairs gastrointestinal motility and duodenal morphometry in moderately exercised rats.

The misuse of anabolic androgenic steroid associated or not with physical workouts disrupts gastrointestinal (GI) function homeostasis. Our goal was to investigate the effects of nandrolone decanoate (ND) and moderate swimming on the GI transit of solid meals, GI motor contractility, and intestinal histology in rats. Male Wistar rats were allocated to four groups that received intramuscular injections of ND (5.0 mg/kg) or vehicle (60.0 µL) and were submitted or not to swimming sessions (60 min, 5% body weight overload) for 4 weeks. Gastric emptying, intestinal transit, in vitro GI contractility, intestinal morphometry, and duodenal mucosal mast cells were evaluated in all experimental groups. ND treatment accelerated gastric emptying, slowed small intestine transit time, enhanced gastric carbachol-mediated reactivity, decreased crypt depth and villus height, reduced mucosal thickness, and increased the circular and longitudinal muscle layer thickness of the duodenum in sedentary rats. Moderate exercise accelerated intestinal transit time and reduced submucosa thickness. In vehicle-treated animals, a strong negative correlation was found between intestinal transit and mucosal mast cells, which was reversed by ND treatment. Combining ND treatment and swimming accelerated gastric emptying, increased duodenal cholinergic reactivity, inhibited the sodium nitroprusside relaxing response, increased the number of duodenal mast cells, decreased villus height, and increased the thickness of all muscle layers. ND changed the morphological and functional properties of the GI tract over time, with intense dysmotility, especially in sedentary animals, but moderate exercise seemed to have played a compensatory role in these harmful effects in the gut.

The effect of pre-operative biliary drainage in resectable periampullary lesions: a systematic review and meta-analysis.

OBJECTIVE: The effect of a pre-operative biliary stent on complications after pancreaticoduodenectomy (PD) remains controversial. MATERIALS AND METHOD: We conducted a meta-analysis according to the preferred reporting items for systematic reviews and meta-analyses guidelines, and PubMed, Web of Science Knowledge, and Ovid's databases were searched by the end of February 2023. 35 retrospective studies and 2 randomized controlled trials with a total of 12641 patients were included. RESULTS: The overall complication rate of the pre-operative biliary drainage (PBD) group was significantly higher than the no-PBD group (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.22-1.74; p < 0.0001), the incidence of post-operative delayed gastric emptying was increased in patients with PBD compared those with early surgery (OR 1.21, 95% CI: 1.02-1.43; p = 0.03), and there was a significant increase in post-operative wound infections in patients receiving PBD with an OR of 2.2 (95% CI: 1.76-2.76; p < 0.00001). CONCLUSIONS: PBD has no beneficial effect on post-operative outcomes. The increase in post-operative overall complications and wound infections urges the exact indications for PBD and against routine pre-operative biliary decompression, especially for patients with total bilirubin < 250 umol/L waiting for PD.

OBJETIVO: El efecto de una endoprótesis biliar pre-operatoria sobre las complicaciones después de la pancreaticoduodenectomía sigue siendo controvertido. MATERIALES Y MÉTODO: Se llevó a cabo un metaanálisis siguiendo las directrices PRISMA y se realizaron búsquedas en PubMed, Web of Science Knowledge y la base de datos de Ovid hasta finales de febrero de 2023. Se incluyeron 35 estudios retrospectivos y 2 ensayos controlados aleatorizados, con un total de 12,641 pacientes. RESULTADOS: La tasa global de complicaciones del grupo drenaje biliar pre-operatorio (PBD) fue significativamente mayor que la del grupo no-PBD (odds ratio [OR]: 1.46; intervalo de confianza del 95% [IC 95%]: 1.22-1.74; p < 0.0001), la incidencia de vaciado gástrico retardado posoperatorio fue mayor en los pacientes con PBD en comparación con los de cirugía precoz (OR: 1.21; IC95%: 1.02-1.43; p = 0.03), y hubo un aumento significativo de las infecciones posoperatorias de la herida en los pacientes que recibieron PBD (OR: 2.2; IC 95%: 1.76-2.76; p < 0.00001). CONCLUSIONES: El drenaje biliar pre-operatorio no tiene ningún efecto beneficioso sobre el resultado posoperatorio. El aumento de las complicaciones posoperatorias globales y de las infecciones de la herida urge a precisar las indicaciones de PBD y a desaconsejar la descompresión biliar pre-operatoria sistemática, en especial en pacientes con bilirrubina total inferior a 250 µmol/l en espera de pancreaticoduodenectomía.

Moderate physical exercise and ATP modulate the P2X7 receptor and improve cisplatin-induced gastric emptying delay in rats.

Patients undergoing chemotherapy with cisplatin commonly present gastrointestinal effects such as constipation and gastric emptying (GE) delay. Both the purinergic system and physical exercise modulate the gastrointestinal (GI) tract. In the current study, we investigated the role of ATP, physical exercise, and P2X7 receptor blocking on GE delay induced by cisplatin in rats. Male rats were divided into the following groups: control (C), cisplatin (Cis), exercise (Ex), Brilliant Blue G (BBG), ATP, Cis+Ex, Cis+ATP, Cis+BBG, Cis+Ex+BBG, Cis+Ex+BBG+ATP, and Cis+ATP+BBG. GE delay was induced by treatment with 1 mg/kg cisplatin (1 time/week for 5 weeks, ip). The moderate physical exercise was swimming (1 h/day, 5 days/week for 5 weeks). At the end of the treatment or exercise and 30 min before the GE assessment, some groups received BBG (50 mg/kg, sc) or ATP (2 mg/kg, sc). Then, GE was assessed after a 10-min postprandial period. Chronic use of Cis decreased GE delay (P<0.05) compared to the control group. Both exercise and ATP prevented (P<0.05) GE delay compared to Cis. The pretreatment with BBG significantly inhibited (P<0.05) the effect of exercise and ATP. On the other hand, the association between exercise and ATP reversed (P<0.05) the effect of the BBG and prevented GE delay. Therefore, we suggest that both exercise and treatment with ATP activate P2X7 receptors and prevent GE delay induced by cisplatin in rats.

Delayed gastric emptying after pancreatoduodenectomy: an analysis of risk factors.

BACKGROUND: Delayed gastric emptying (DGE) is a frequent complication after pancreatoduodenectomy. Preoperative factors are limited and controversial. This study aims to identify associated factors related to this complication in the Colombian population. METHODS: A retrospective review of a prospectively collected database was conducted. All patients over 18 years of age who underwent pancreaticoduodenectomy were included. Associations with DGE syndrome were evaluated with logistic regression analysis, Odds ratio, and b-coefficient were provided when appropriate. RESULTS: 205 patients were included. Male patients constituted 54.15% (n = 111). 53 patients (25.85%) were diagnosed with DGE syndrome. Smoking habit (OR 17.58 p 0.00 95% CI 7.62-40.51), hydromorphone use > 0.6 mg/daily (OR 11.04 p 0.03 95% CI 1.26-96.66), bilirubin levels > 6 mg/dL (OR 2.51 p 0.02 95% CI 1.12-5.61), and pancreatic fistula type B (OR 2.72 p 0.02 CI 1.74-10.00). DISCUSSION: Smoking history, opioid use (hydromorphone > 0.6 mg/Daily), type B pancreatic fistula, and bilirubin levels > 6 mg/dL should be considered as risk factors for DGE.

RESIDUAL GASTRIC VOLUME IN MORBIDLY OBESE DIABETICS AFTER AN OVERNIGHT FASTING OR 3 HOURS OF A CARBOHYDRATE-ENRICHED SUPPLEMENT: A RANDOMIZED CROSSOVER PILOT STUDY.

BACKGROUND: To reduce the risk of regurgitation during anesthesia for elective procedures, residual gastric volumes (RGV) have traditionally been minimized by overnight fasting. Prolonged preoperative fasting presents some adverse consequences and has been abandoned for most surgical procedures, except for obese and/or diabetic patients. AIMS: The aim of this study was to assess the RGV in morbidly obese diabetic patients after traditional or abbreviated fasting. METHODS: This study was approved by the Ethics Committee for Research with Human Beings from the Federal University of Mato Grosso, under number 179.017/2012. This is a prospective, randomized, and crossover design study in eight morbidly obese type II diabetic patients. RGV was measured endoscopically after either traditional overnight fasting of at least 8 hours, or after abbreviated fasting of 6 hours for solids and 3 hours for a drink containing water plus 25 g (12.5%) of maltodextrin. Data were expressed as mean and range and differences were compared with paired t-tests at p<0.05. RESULTS: The study population had a mean age of 41.5 years (28-53), weight of 135 kg (113-196), body mass index of 48.2 kg/m2 (40-62.4), and type II diabetes for 4.5 years (1-10). The RGV after abbreviated fasting was 21.5 ml (5-40) vs 26.3 ml (7-65) after traditional fasting. This difference was not significant (p=0.82). CONCLUSIONS: Gastric emptying in morbidly obese diabetic patients is similar after either traditional or abbreviated fasting with a carbohydrate drink.

Pharmacomagnetography assessment of the prokinetic effect on metronidazole absorption.

OBJECTIVES: This study aimed to evaluate the effects of prucalopride, a prokinetic agent that acts as a potent serotonin agonist of 5-HT4 receptors, on gastric emptying and small bowel transit and assess its impact on the absorption of metronidazole. METHODS: Six healthy volunteers, three men and three women, aged between 20 and 27 years, with a body weight ranging from 50 to 80 kg, were enrolled in this study. The pharmacokinetics and gastrointestinal transit parameters were evaluated simultaneously through pharmacomagnetography assessment, combining alternating current biosusceptometry and blood analysis. KEY FINDINGS: The results showed that prucalopride enhances gastric emptying and small bowel transit when administered orally and significantly impacts the rate of metronidazole absorption, leading to enhanced bioavailability and rapid therapeutic response. CONCLUSION: Pharmacomagnetography assessment allows simultaneous tracking of transit by images and is a valuable method for analysing drug absorption using multiple instruments.

Alternate-day fasting induces metabolic and morphofunctional changes in the gastrointestinal tract of male rats.

Alternate-day fasting (ADF) is a nutritional intervention with modulatory and overall protective effects, but its role in the gastrointestinal (GI) tract is still uncertain. The aim of this study was to investigate the influence of ADF on the metabolic patterns and morphofunctional motility of the GI tract in rats. Thirty-two male Wistar rats were allocated into groups: control for 15 days (CON 15, n = 8), control for 30 days (CON 30, n = 8), ADF for 15 days (ADF 15, n = 8), and ADF for 30 days (ADF 30, n = 8). Blood glucose, body weight, and food and water consumption were measured. Frequency and amplitude of gastric contractions as well as gastric emptying time, small intestinal transit time, and cecum arrival time were measured. Intestinal histomorphometric, relative weight of organs, lipidogram, and leptin levels were also evaluated. ADF decreased water consumption and food consumption. The weight gain decreased; however, the relative kidney weight increased. ADF triggered an increase in the amplitude of gastric contractions and accelerated gastric emptying. However, small intestinal transit time was delayed in both ADF groups. Total cholesterol, triglycerides, non-HDL cholesterol, and very low-density lipoprotein cholesterol levels decreased, whereas villus height, depth of the crypts and thickness of the circular, and longitudinal muscular layers of intestine increased after ADF. In conclusion, our results showed ADF exert an effect on both metabolism and GI motility and impacts on overall digestive functions.

GASTROINTESTINAL MOTILITY IN ELDERLY PATIENTS WITH WELL-CONTROLLED TYPE 2 DIABETES MELLITUS.

BACKGROUND: Gastrointestinal (GI) motility disorders in type 2 diabetes mellitus (T2DM) are common. However, the endpoints in well-controlled T2DM in elderly patients are barely understood. OBJECTIVE: To evaluate GI transit and gastric myoelectric activity in elderly patients with T2DM who were undergoing treatment with metformin and to compare them with non-diabetic healthy controls. METHODS: A total of thirty participants were enrolled in this study: young non-diabetic (n=10), elderly non-diabetic controls (n=10), and patients with T2DM managed with metformin (n=10). After fasting overnight, the participants ingested a standard meal and magnetic markers for non-invasive monitoring of GI transit and gastric contractility using the alternating current biosusceptometry and electrogastrography techniques. RESULTS: Mean gastric emptying time, mean colon arrival time, and mean intestinal transit time were determined. There were no significant differences between the groups and in the parameters evaluated (P>0.05). The frequency and amplitude of gastric myoelectric activity were not different between groups; however, abnormal rhythmic index and the half-bandwidth were slightly higher for both elderly diabetic and non-diabetic groups compared with the young adults (P<0.01 and P<0.05, respectively). CONCLUSION: Our study showed unaltered gastric emptying and intestinal transit in T2DM patients with good glycemic control, and suggest changes in the gastric electrical activity can be a part of aging.

Sleeve Gastrectomy with Pyloroplasty in Wistar Rats: Assessment of Gastric Emptying, Intestinal Transit, and Possible Duodenogastric Alkaline Reflux.

BACKGROUND: Studies indicate sleeve gastrectomy (SG) as a factor of aggravation or even emergence of symptoms of gastroesophageal reflux disease. Accelerated gastric emptying is described as a mitigating factor. SG may be potentiated by adding a pyloroplasty, although with the potential risk of resulting in duodenogastric alkaline reflux. The objective was to standardize sleeve gastrectomy with pyloroplasty in rats, analyze the complementation in terms of mortality and weight evolution, and conduct assessments on gastric emptying, intestinal transit, and genesis of possible duodenogastric reflux. METHODS: Ninety-three male Wistar rats were divided into a pilot study (standardization of the surgical technique and the scintigraphic study), and the main study. They were then subdivided into the SHAM group, the sleeve gastrectomy (SG) group, and the sleeve gastrectomy with pyloroplasty (SGP) group. After 3 months, the animals were submitted to two scintigraphic experiments and histological analysis of gastric biopsies. RESULTS: The surgical groups (SG and SGP) lost initially more weight than the SHAM group, and the gastric emptying and intestinal transit in the first were more accelerated. However, no difference was found between the SG and SGP groups. Scintigraphic and histological analyses did not reveal statistical differences among the SG and SGP groups regarding gastroesophageal and duodenogastric refluxes. CONCLUSIONS: Pyloroplasty did not affect weight reduction or increase duodenogastric reflux, after three postoperative months in this animal model of sleeve gastrectomy.

Vomiting and Gastric Motility in Early Brain Damaged Children With Congenital Zika Syndrome.

OBJECTIVES: This study investigated the occurrence of vomiting and gastric dysmotility in dysphagic children with congenital Zika syndrome (CZS) and assessed possible associations of these findings with the severity of dysphagia and the presence of tube feeding. METHODS: Forty-six children with CZS were assessed for dysphagia, and the occurrence of vomiting, dietary volume tolerance <15 mL/kg, and feeding time per meal >30 minutes were evaluated. Gastric antrum ultrasonography was used to detect the frequency of contractions and measure antral areas (at fasting and 15 minutes postprandial), from which the gastric emptying rate (GER) was calculated. Antral ultrasonography findings were compared with those of ten healthy controls. Vomiting and gastric motility were compared between CZS patients according to the severity of dysphagia and the requirement for tube feeding. RESULTS: Overall, 76% (35/46) of children with CZS had moderate-to-severe dysphagia (MSD), among whom 60% (21/35) were tube fed [MSD tube fed (MSDTF)]. Vomiting occurred in 54% (25/46) of children, whereas dietary volume intolerance and prolonged feeding time were observed in 59% (27/46) and 37% (17/46), respectively, most frequently in MSDTF patients. On ultrasound, 61% (28/46) of children with CZS had no antral contractions, whereas 90% (9/10) of controls did. Compared to healthy controls, GER was eight-fold lower in children with CZS and 60-fold lower in MSDTF children. CONCLUSIONS: In dysphagic children with CZS, vomiting, volume intolerance, and prolonged feeding time were frequent and possibly associated with impaired antral contraction and delayed gastric emptying, especially in cases of severe dysphagia and tube feeding.

Gastric peroral endoscopic myotomy outcomes after 4 years of follow-up in a large cohort of patients with refractory gastroparesis (with video).

BACKGROUND AND AIMS: Gastric peroral endoscopic myotomy (G-POEM) is used for refractory gastroparesis (RG) with good early-term but variable mid- and long-term outcomes. Limited data exist about candidates and long-term clinical and predictive factors. Our aim was to evaluate the 4-year follow-up efficacy and predictive factors in patients with RG. METHODS: Confirmed RG patients were included and evaluated between April 2017 and December 2021. Gastroparesis Cardinal Symptom Index (GCSI) score, retention percentage at 4 hours (RP4H), mean half-emptying time (MHET), and the 36-item short-form survey (SF-36) were performed at 1, 6, 12, 18, 24, 30, 36, 42, and 48 months. RESULTS: After G-POEM, 374 patients with RG were included: 141 patients (37.7%) had diabetic gastroparesis (DG), 115 (30.7%) had idiopathic gastroparesis (IG), 102 (27.3%) had postsurgical gastroparesis (PSG), and 16 (4.3%) had other etiologies. After the 48-month evaluation, 102 patients completed follow-up (DG, 58; IG, 22; PSG, 18; other, 4). Before G-POEM, GCSI score, RP4H, and MHET were 3.84 ± .53, 44% (interquartile range [IQR], 11-68), and 246 minutes (IQR, 150-368), respectively, and after the 48-month evaluation improved to 2.1 ± .70 (P < .001), 15.5% (IQR, 0-36; P = .021), and 135 minutes (IQR, 67-290; P = .045), respectively. At the 48-month evaluation, clinical success was 77.5%. DG showed the best outcomes (DG vs IG vs PSG vs other: 86.5% vs 72.5% [P = .001] vs 72.1% [P = .003] vs 68.8% [P < .001]). Long-term success predictors were DG (odds ratio [OR], 5.113; 95% confidence interval [CI], 1.643-5.981; P = .035), early diagnosis (OR, 2.455; 95% CI, 1.129-3.522; P = .042), nausea/vomiting (OR, 3.541; 95% CI, 1.881-5.511; P = .012), GCSI score at 6 months (1.5-2) (OR, 3.612; 95% CI, 2.122-5.317; P = .022), and RP4H <10% at 6 months (OR, 2.188; 95% CI, 1.435-4.233; P = .039). CONCLUSIONS: G-POEM is an effective 4-year treatment in patients with RG, especially in DG, establishing a potential first-line therapy in these patients. However, randomized controlled clinical trials are needed to confirm these results. (Clinical trial registration number: NTC03126513.).

Reporte de un caso de tratamiento de gastroparesia pediátrica con prucaloprida: una terapia novedosa / A case report of prucalopride treatment in pediatric gastroparesis: a novel therapy

La prucaloprida acelera el vaciamiento gástrico en adultos con gastroparesia. No existen estudios con este medicamento en niños con gastroparesia. Se presenta un niño de 8 años que consultó por síntomas posprandiales de un mes de duración, con diagnóstico de gastroparesia por gammagrafía de vaciamiento gástrico. No mejoró con metoclopramida, domperidona, eritromicina y esomeprazol. Recibió prucaloprida durante dos períodos (durante 178 y 376 días) a dosis de 0,03-0,04 mg/kg/día. Presentó mejoría en el seguimiento con el índice cardinal de síntomas de gastroparesia y gammagrafías de vaciamiento gástrico. Por la buena respuesta, la prucaloprida podría ser una opción terapéutica en la gastroparesia pediátrica.

Prucalopride has been used in adults with gastroparesis, accelerating gastric emptying. There are no studies with this drug in gastroparetic children. An 8-year-old boy is presented who consulted for a month of postprandial symptoms, with a diagnosis of gastroparesis by gastric emptying scintigraphy. He did not improve with metoclopramide, domperidone, erythromycin, and esomeprazole. He received prucalopride for two periods (for 178 and 376 days) at doses: 0.03 - 0.04 mg/kg/day, presenting improvement in the follow-up with the cardinal gastroparesis symptom index and gastric emptying scintigraphy. Due to the good response, prucalopride may be a therapeutic option in pediatric gastroparesis.

A case report of prucalopride treatment in pediatric gastroparesis: a novel therapy. / Reporte de un caso de tratamiento de gastroparesia pediátrica con prucaloprida: una terapia novedosa.

Prucalopride has been used in adults with gastroparesis, accelerating gastric emptying. There are no studies with this drug in gastroparetic children. An 8-year-old boy is presented who consulted for a month of postprandial symptoms, with a diagnosis of gastroparesis by gastric emptying scintigraphy. He did not improve with metoclopramide, domperidone, erythromycin, and esomeprazole. He received prucalopride for two periods (for 178 and 376 days) at doses: 0.03 - 0.04 mg/ kg/day, presenting improvement in the follow-up with the cardinal gastroparesis symptom index and gastric emptying scintigraphy. Due to the good response, prucalopride may be a therapeutic option in pediatric gastroparesis.

La prucaloprida acelera el vaciamiento gástrico en adultos con gastroparesia. No existen estudios con este medicamento en niños con gastroparesia. Se presenta un niño de 8 años que consultó por síntomas posprandiales de un mes de duración, con diagnóstico de gastroparesia por gammagrafía de vaciamiento gástrico. No mejoró con metoclopramida, domperidona, eritromicina y esomeprazol. Recibió prucaloprida durante dos períodos (durante 178 y 376 días) a dosis de 0,03-0,04 mg/kg/ día. Presentó mejoría en el seguimiento con el índice cardinal de síntomas de gastroparesia y gammagrafías de vaciamiento gástrico. Por la buena respuesta, la prucaloprida podría ser una opción terapéutica en la gastroparesia pediátrica.

Effect of anaerobic resistance training on gastric emptying of solids, nutritional parameters and food behavior in the rats treated with dexamethasone.

Dexamethasone (Dexa) is a potent glucocorticoid that can trigger side effects, such as neuromuscular, cardiovascular, and gastric motility disorders. Exercise can ameliorate gastrointestinal disorders. However, it is not clear whether exercise can modulate the side effects of using Dexa on gastric motility. To investigate the role of anaerobic resistance training (ART) on gastric motility and feeding behavior of rats treated with dexamethasone, rats were divided into three groups: control (Ctrl), dexamethasone (Dexa), and anaerobic resistance training + dexamethasone (ARTDexa). Anaerobic resistance training (ART) consisted of climbing a vertical ladder 5 days/week (with intensity of 50% to 100% of the maximum overload/8 weeks). At the end of the ART or control period, the rats received Dexa (1 mg/kg i.p) for 10 consecutive days. In the end, we evaluated anthropometric parameters and feeding behavior, heart rate, gastric emptying, and lipid profile in all groups. We observed significant decrease (p < 0.05) in body weight and food intake in the Dexa and ARTDexa groups compared to the control. Dexa promoted significant tachycardia (p < 0.05) and a decrease (p < 0.05) in the r-r' interval. The ART significantly prevented (p < 0.05) cardiovascular effects. Dexa induced a decrease (p < 0.05) in gastric emptying compared to the control group. On the other hand, ART significantly prevented (p < 0.05) the decrease in gastric emptying compared to Dexa. The chronic use of Dexa caused tachycardia, decreased food intake, and decreased gastric emptying. The ART modulated cardiovascular parameters, improving tachycardia. In addition, this exercise prevented gastric dysmotility induced by dexamethasone.

Brazil Nut (Bertholletia excelsa H.B.K) Retards Gastric Emptying and Modulates Enteric Glial Cells in a Dose-Dependent Manner.

BACKGROUND: The role of food and nutrients in the regulation of enteric glial cell functions is unclear. Some foods influence enteric neurophysiology and can affect glial cell functions that include regulation of the intestinal barrier, gastric emptying, and colonic transit. Brazil nuts are the most abundant natural source of selenium, unsaturated fatty acids, fibers, and polyphenols. OBJECTIVE: The study investigated the effects of a Brazil nut-enriched diet on enteric glial cells and gastrointestinal transit. METHODS: Two-month-old male Wistar rats were randomized to a standard diet (control group, CG), standard diet containing 5% (wt/wt) Brazil nut (BN5), and standard diet containing 10% (wt/wt) Brazil nut (BN10) (n = 9 per group). After eight weeks, the animals underwent constipation and gastric emptying tests to assess motility. Evaluations of colonic immunofluorescence staining for glial fibrillary acidic protein (GFAP) and myenteric ganglia area were performed. RESULTS: The BN5 group showed increased weight gain while the BN10 group did not (p < 0.0001). The BN10 group showed higher gastric residue amounts compared to the other groups (p = 0.0008). The colon exhibited an increase in GFAP immunoreactivity in the BN5 group compared to that in the other groups (p = 0.0016), and the BN10 group presented minor immunoreactivity compared to the CG (p = 0.04). The BN10 group presented a minor ganglia area compared to the CG (p = 0.0155). CONCLUSION: The Brazil nut-enriched diet modified the gastric residual, colonic GFAP immunoreactivity, and myenteric ganglia area after eight weeks in healthy male Wistar rats.

Involvement of MT2 receptors in protective effects of melatonin against cisplatin-induced gastrointestinal damage in mice

Abstract Melatonin (MLT) reportedly reduces side effects associated with certain antineoplastic agents. Accordingly, we investigated the effect of MLT on cisplatin (CP)-induced gastric emptying (GE) delay. Mice were intraperitoneally pretreated with vehicle (ethanol 5%; control group), MLT (5, 10, or 20 mg/kg), or N-acetylcysteine (NAC; 150 mg/kg), followed by CP treatment (5 mg/kg). Pharmacological modulation was analyzed using relevant receptor antagonists (luzindole: non-selective MT1/MT2 antagonist; 5 mg/kg or 4-P-PDOT: selective MT2 antagonist; 4 mg/kg) before treatment with MLT plus CP. All treatments were performed once daily for three days. GE was assessed using phenol red. Gut morphology was examined using scanning electron microscopy and optical microscopy. Compared with the control, CP decreased GE. Pretreatment with NAC and MLT (5 and 10 mg/kg) did not prevent CP-induced gastric dysmotility; however, pretreatment with 20 mg/kg MLT prevented this effect. In addition, luzindole and 4-P-PDOT suppressed MLT-mediated gastroprotection against cytotoxic effects of CP. CP caused degeneration of the gut mucosa, which was attenuated by MLT treatment. Thus, 20 mg/kg MLT prevented the GE delay and decreased CP-induced adverse effects on the gut mucosa. In addition, the gastroprotective activity was mediated via the MT2 receptor.

Formulation, Optimization, in vitro and in-vivo evaluation of levofloxacin hemihydrate Floating Tablets

Abstract The objective of the present investigation was to design, optimize and characterize the gastro retentive floating levofloxacin tablets and perform in-vivo evaluation using radiographic imaging. The floating tablets were prepared by using polymers i.e hydroxy propyl methyl cellulose (HPMC-K4M) and carbopol-940 individually and in combination by nonaquous granulation method. All the Formulations were evaluated for swelling index (S.I), floating behavior and in-vitro drug release kinetics. The compatibility study of levofloxacin with other polymers was investigated by FTIR, DSC, TGA and XRD. Results from FTIR and DSC revealed no chemical interaction amongst the formulation components. The optimized formulation (F11) showed floating lag time (FLT), total floating time (TFT) swelling index (S.I) of 60 sec, >16h and approximately 75 %, respectively. Moreover, F11 showed zero order levofloxacin release in simulated gastric fluid over the period of 6 h. X-ray studies showed that total buoyancy time was able to delay the gastric emptying of levofloxacin floating tablets in rabbits for more than 4 hours. In conclusion the optimized formulation (F11) can be used for the sustained delivery of levofloxacin for the treatment of peptic ulcer.

Classification of gastric emptying and orocaecal transit through artificial neural networks.

Classical quantification of gastric emptying (GE) and orocaecal transit (OCT) based on half-life time T$ _{50} $, mean gastric emptying time (MGET), orocaecal transit time (OCTT) or mean caecum arrival time (MCAT) can lead to misconceptions when analyzing irregularly or noisy data. We show that this is the case for gastrointestinal transit of control and of diabetic rats. Addressing this limitation, we present an artificial neural network (ANN) as an alternative tool capable of discriminating between control and diabetic rats through GE and OCT analysis. Our data were obtained via biological experiments using the alternate current biosusceptometry (ACB) method. The GE results are quantified by T$ _{50} $ and MGET, while the OCT is quantified by OCTT and MCAT. Other than these classical metrics, we employ a supervised training to classify between control and diabetes groups, accessing sensitivity, specificity, $ f_1 $ score, and AUROC from the ANN. For GE, the ANN sensitivity is 88%, its specificity is 83%, and its $ f_1 $ score is 88%. For OCT, the ANN sensitivity is 100%, its specificity is 75%, and its $ f_1 $ score is 85%. The area under the receiver operator curve (AUROC) from both GE and OCT data is about 0.9 in both training and validation, while the AUCs for classical metrics are 0.8 or less. These results show that the supervised training and the binary classification of the ANN was successful. Classical metrics based on statistical moments and ROC curve analyses led to contradictions, but our ANN performs as a reliable tool to evaluate the complete profile of the curves, leading to a classification of similar curves that are barely distinguished using statistical moments or ROC curves. The reported ANN provides an alert that the use of classical metrics can lead to physiological misunderstandings in gastrointestinal transit processes. This ANN capability of discriminating diseases in GE and OCT processes can be further explored and tested in other applications.

WHAT FACTORS CONTRIBUTE TO DELAYED GASTRIC EMPTYING AFTER DUODENOPANCREATECTOMY WITH PILORIC PRESERVATION?

BACKGROUND: The delay in gastric emptying is the second most frequent complication after duodenopancreatectomy with pyloric preservation, that increases hospitalization time and hospital costs. AIM: To identify factors that contribute to the appearance the delay in this surgical procedure. METHOD: Ninety-five patients were submitted to duodenopancreatectomy with pyloric preservation. After retrospective analysis of the medical records, it was observed that 60 had prolonged hospitalization due to complications. Thus, univariate and multivariate logistic regression were used to analyze predictors of delayed gastric emptying. RESULTS: Delay was present in 65% (n=39) and pancreatic fistula in 38.3% (n=23). Univariate analysis revealed that the presence of pancreatic complications (pancreatic fistula, p=0.01), other intracavitary complications with the appearance of abdominal collections (p=0.03) and hypoalbuminemia (p=0.06) were responsible, also confirmed by the multivariate analysis. In those who presented delay without a determined cause, it was observed that high levels of total bilirubin (p=0.01) and direct bilirubin (p=0.01) could be related to it. CONCLUSION: The delay in gastric emptying in patients undergoing duodenopancreatectomy with pyloric preservation is due to intracavitary complications.