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Brazilian Journal of Medical and... 2024Patients undergoing chemotherapy with cisplatin commonly present gastrointestinal effects such as constipation and gastric emptying (GE) delay. Both the purinergic...
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.
Topics: Animals; Cisplatin; Male; Adenosine Triphosphate; Gastric Emptying; Receptors, Purinergic P2X7; Physical Conditioning, Animal; Rats, Wistar; Antineoplastic Agents; Rats; Purinergic P2X Receptor Antagonists
PubMed: 38716980
DOI: 10.1590/1414-431X2024e13234 -
Cureus Apr 2024Post-prandial hyperglycemia (PPHG) remains a complex aspect in the management of type 2 diabetes mellitus (T2DM) in the Indian population due to uncertainty in the...
BACKGROUND
Post-prandial hyperglycemia (PPHG) remains a complex aspect in the management of type 2 diabetes mellitus (T2DM) in the Indian population due to uncertainty in the optimal utilization of alpha-glucosidase inhibitors (AGIs) either as standalone therapy or in combination, whether initiated initially or as a sequential therapy.
METHODS
This was a post-approval, observational, multicentric clinical study conducted at 50 centers according to principles of the International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use Guideline for Good Clinical Practice (ICH-GCP) and Declaration of Helsinki and local ethics approval. Descriptive and analytical statistics were applied for conclusion and categorical variables using SPSS version 29.0.1.0 (171) (Armonk, NY: IBM Corp.).
RESULTS
Protocol analyses of 515 cases revealed baseline demographics as follows: age 57.35±10.04 years, weight 72.86±10.92 kg, and BMI 28.33±6.07 kg/m. Comorbidities included hypertension (N=169, 32.82%), thyroid disorders (N=99, 19.22%), and heart failure (N=92, 17.86%). Concomitant oral antidiabetics (OADs) prescribed as DPP4i (9.50%), SGLT2i (19.20%), and DPP4i+SGLT2i (7.20%). Study drug reduced glycosylated hemoglobin (HbA1c) by 13.77% (1.25% mean change, p<0.01), fasting blood glucose (FBG) by 23.69% (44.61 mg/dL mean change, p<0.01), post-prandial blood glucose (PPBG) by 24.57% (70.46 mg/dL mean change, p<0.01), and body weight by 4.43% (3.21 kg mean change, p<0.01) over 12 weeks. A total of 161 patients accomplished targeted PPBG of <180 mg/dL (119.13 mg/dL mean change, p<0.01). Regression analysis considering PPBG and HbA1c ≤7.5% showed a weak correlation between them (R-value=0.13, R-squared value=0.02), whereas between PPBG and HbA1c ≤9% yielded moderate positive correlation (R-value=0.53, R-squared value=0.28). There were no adverse events reported or analyzed during the observation period.
CONCLUSION
Voglibose fixed-dose combination (FDC) demonstrates significant effectiveness at the initial dosage when started early in the management of T2DM and high PPBG levels. Moreover, it exhibits good tolerability, thereby contributing to higher compliance among Indian patients who consume a high-carbohydrate diet.
PubMed: 38707131
DOI: 10.7759/cureus.57494 -
European Journal of Pharmaceutical... Jul 2024Physiologically based pharmacokinetic (PBPK) models can help to understand the effects of gastric emptying on pharmacokinetics and in particular also provide a platform...
Physiologically based pharmacokinetic (PBPK) models can help to understand the effects of gastric emptying on pharmacokinetics and in particular also provide a platform for understanding mechanisms of food effects, as well as extrapolation between different postprandial conditions, whether standardized clinical or patient-oriented, non-clinical conditions. By integrating biorelevant dissolution data from the GastroDuo dissolution model into a previously described mechanistic model of fed-state gastric emptying, we simulated the effects of a high-calorie high-fat meal on the pharmacokinetics of sildenafil, febuxostat, acetylsalicylic acid, theobromine and caffeine. The model was able to simulate the variability in C and t caused by the presence of the stomach road. The main influences investigated to affect the gastric emptying process were drug solubility (theobromine and caffeine), tablet dissolution rate (acetylsalicylic acid) and sensitivity to gastric motility (sildenafil and febuxostat). Finally, we showed how PBPK models can be used to extrapolate pharmacokinetics between different prandial states using theobromine as an example with results from a clinical study being presented.
Topics: Gastric Emptying; Postprandial Period; Humans; Models, Biological; Computer Simulation; Solubility; Febuxostat; Theobromine; Caffeine; Sildenafil Citrate; Drug Liberation; Aspirin
PubMed: 38705421
DOI: 10.1016/j.ejps.2024.106788 -
Cancer Chemotherapy and Pharmacology May 2024This study assessed effect of food on pharmacokinetics (PK) and safety of fuzuloparib capsules.
PURPOSE
This study assessed effect of food on pharmacokinetics (PK) and safety of fuzuloparib capsules.
METHODS
A randomized, open-label, two-cycle, two-sequence, crossover clinical trial was conducted. 20 subjects were randomly assigned to 2 groups at a 1:1 ratio. The first group subjects were orally administered 150 mg fuzuloparib capsules under fasting condition in first dosing cycle. The same dose of fuzuloparib capsules were taken under postprandial state after a 7-day washout period. The second group was reversed. 3 ml whole blood was collected at each blood collection point until 72 h post dose. PK parameters were calculated. Furthermore, safety assessment was performed.
RESULTS
The time to maximum concentration (T) was prolonged to 3 h and maximum concentration (C) decreased by 18.6% on high-fat diets. 90% confidence intervals (CIs) of geometric mean ratios (GMRs) for C, area under the concentration-time curve from time zero to time t (AUC), and area under the concentration-time curve extrapolated to infinity (AUC) after high-fat meal were 71.6-92.6%, 81.7-102.7% and 81.6-102.5%, respectively. All treatment-emergent adverse events (TEAEs) were grade 1; No serious adverse events (SAEs), serious unexpected suspected adverse reaction (SUSAR) or deaths were reported.
CONCLUSION
Food decreased the absorption rate and slowed time to peak exposure of fuzuloparib capsules, without impact on absorption extent. Dosing with food was found to be safe for fuzuloparib capsules in this study.
CLINICAL TRIAL REGISTRATION
This study was registered with chinadrugtrials.org.cn (identifier: CTR20221498).
PubMed: 38703321
DOI: 10.1007/s00280-024-04672-6 -
Obesity Surgery Jun 2024In recent years, numerous studies have tried to decode the way bariatric surgery works toward weight reduction by the use of food preference questionnaires. The...
BACKGROUNDS
In recent years, numerous studies have tried to decode the way bariatric surgery works toward weight reduction by the use of food preference questionnaires. The intragastric balloon has gained popularity, mainly due to its limited invasiveness, in patients with obesity not fulfilling criteria for bariatric surgery. However, there is no study assessing the changes in food preferences [FP]. We decided to analyze the FP of individuals prior to intragastric balloon insertion and following its removal, on the strict condition that participants must complete the 6-month treatment period and attend at least 4 of the 7 follow-up interviews.
METHODS
Patients were asked to rate the frequency of consumption of 63 food items before balloon insertion, at monthly intervals and after balloon removal. The food categories were protein, carbohydrates, fruit and vegetables, and sweets and fats.
RESULTS
The questionnaires of 320 participants were analyzed. A reduced frequency in consumption of meat and meat products, high-fat, and high-carbohydrate/sugary products and an increase in raw vegetables and fruit was found in all individuals.
CONCLUSION
The intragastric balloon seems to exert analogically similar mechanisms to bariatric surgery for weight loss, both functioning through alterations in FP. These are dictated by the anatomical re-configuration of the stomach, but mainly by counseling of dieticians and the self-education of the patient after experiencing unpleasant postprandial discomfort.
Topics: Humans; Gastric Balloon; Female; Male; Food Preferences; Adult; Obesity, Morbid; Weight Loss; Surveys and Questionnaires; Middle Aged; Feeding Behavior
PubMed: 38703243
DOI: 10.1007/s11695-024-07233-1 -
Gut Jun 2024Postprandial, or meal-related, symptoms, such as abdominal pain, early satiation, fullness or bloating, are often reported by patients with disorders of gut-brain... (Review)
Review
Postprandial, or meal-related, symptoms, such as abdominal pain, early satiation, fullness or bloating, are often reported by patients with disorders of gut-brain interaction, including functional dyspepsia (FD) or irritable bowel syndrome (IBS). We propose that postprandial symptoms arise via a distinct pathophysiological process. A physiological or psychological insult, for example, acute enteric infection, leads to loss of tolerance to a previously tolerated oral food antigen. This enables interaction of both the microbiota and the food antigen itself with the immune system, causing a localised immunological response, with activation of eosinophils and mast cells, and release of inflammatory mediators, including histamine and cytokines. These have more widespread systemic effects, including triggering nociceptive nerves and altering mood. Dietary interventions, including a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols, elimination of potential food antigens or gluten, IgG food sensitivity diets or salicylate restriction may benefit some patients with IBS or FD. This could be because the restriction of these foods or dietary components modulates this pathophysiological process. Similarly, drugs including proton pump inhibitors, histamine-receptor antagonists, mast cell stabilisers or even tricyclic or tetracyclic antidepressants, which have anti-histaminergic actions, all of which are potential treatments for FD and IBS, act on one or more of these mechanisms. It seems unlikely that food antigens driving intestinal immune activation are the entire explanation for postprandial symptoms in FD and IBS. In others, fermentation of intestinal carbohydrates, with gas release altering reflex responses, adverse reactions to food chemicals, central mechanisms or nocebo effects may dominate. However, if the concept that postprandial symptoms arise from food antigens driving an immune response in the gastrointestinal tract in a subset of patients is correct, it is paradigm-shifting, because if the choice of treatment were based on one or more of these therapeutic targets, patient outcomes may be improved.
Topics: Humans; Postprandial Period; Brain-Gut Axis; Irritable Bowel Syndrome; Dyspepsia; Abdominal Pain; Gastrointestinal Microbiome
PubMed: 38697774
DOI: 10.1136/gutjnl-2023-331833 -
Journal of Sports Sciences Mar 2024Stair climbing exercise (SE) provides a feasible approach to elevate physical activity, but the effects on metabolic health are unclear. We systematically reviewed the... (Review)
Review
Stair climbing exercise (SE) provides a feasible approach to elevate physical activity, but the effects on metabolic health are unclear. We systematically reviewed the currently available evidence on the effects of SE on fasting and postprandial glycaemia and lipidaemia. Studies were included if they investigated the effects of acute or chronic (at least 2 weeks) SE on fasting and/or postprandial glycaemic (insulin and glucose) and lipidaemic (triacylglycerols and non-esterified fatty acids) responses in healthy, prediabetic or type 2 diabetic adult populations. PubMed, Web of Science and Scopus were searched for eligible studies until July 2022. A total of 25 studies (14 acute and 11 chronic) were eligible for review. Acute bout(s) of SE can reduce postprandial glycaemia in individuals with prediabetes and type 2 diabetes (8 of 9 studies), but not in normoglycemic individuals. The effects of acute SE on postprandial lipidaemic responses and SE training on both fasting and postprandial glycaemia/lipidaemia were unclear. Acute SE may reduce postprandial glucose concentrations in people with impaired glycaemic control, but high-quality studies are needed. More studies are needed to determine the effect of chronic SE training on postprandial glucose and lipid responses, and the acute effects of SE on lipid responses.
Topics: Humans; Postprandial Period; Blood Glucose; Diabetes Mellitus, Type 2; Stair Climbing; Fasting; Prediabetic State; Insulin; Triglycerides; Fatty Acids, Nonesterified; Lipids
PubMed: 38695325
DOI: 10.1080/02640414.2024.2345414 -
Journal of Oleo Science 2024A double-blind, placebo-controlled, crossover trial was performed to analyze the effects of a small amount of lysolecithin and canola oil on blood glucose levels after... (Randomized Controlled Trial)
Randomized Controlled Trial
Assessing the Postprandial Glycemic Response to Japonica Rice (Oryza sativa L. cv. Koshihikari) with a Small Amount of Lysolecithin and Canola Oil in Japanese Adult Men: a Double-blind, Placebo-controlled, Crossover Study.
A double-blind, placebo-controlled, crossover trial was performed to analyze the effects of a small amount of lysolecithin and canola oil on blood glucose levels after consuming japonica rice. Overall, 17 Japanese adult men were assigned to consume 150 g of normally cooked japonica rice (placebo group) and 150 g of japonica rice cooked with 18 mg of lysolecithin and 1.8 g of canola oil (treatment group); these lipids were added as emulsified formulation (EMF) for stability and uniformity. Subsequently, blood samples were collected before and 30, 45, 60, 90, and 120 min after consuming test foods. There was no significant difference in blood glucose, insulin, and triglyceride levels between the groups. However, a stratified analysis of 11 subjects with body mass index (BMI) ≥ 22 revealed that blood glucose levels were significantly lower after 30 min in the treatment group than in the placebo group (p = 0.041). Through in vitro digestibility test, the rice sample of the treatment group was observed to release significantly less glucose within 20 min than that in the placebo group rice. These results suggest that the combination of a small amount of lysolecithin and canola oil modulated the increase in postprandial blood glucose levels induced by the intake of cooked japonica rice in adult men with BMI ≥ 22. This clinical trial was registered with the University Hospital Medical Information Network (UMIN) Center, (UMIN000045744; registered on 15/10/2021).
Topics: Adult; Humans; Male; Middle Aged; Blood Glucose; Body Mass Index; Cross-Over Studies; Double-Blind Method; East Asian People; Glycemic Index; Insulin; Oryza; Postprandial Period; Rapeseed Oil; Time Factors; Triglycerides
PubMed: 38692897
DOI: 10.5650/jos.ess23260 -
Cleveland Clinic Journal of Medicine May 2024Functional dyspepsia is defined as persistent symptoms of postprandial bloating, early satiety, or pain in the center of the upper abdomen, without findings on upper... (Review)
Review
Functional dyspepsia is defined as persistent symptoms of postprandial bloating, early satiety, or pain in the center of the upper abdomen, without findings on upper endoscopy such as peptic ulcer disease to explain these symptoms. It is common, affecting up to 30% of the global population, but it often goes undiagnosed for years. There are 2 subtypes: epigastric pain syndrome (burning and pain) and postprandial distress syndrome (bloating and satiety). The authors discuss how to diagnose and treat both subtypes.
Topics: Humans; Dyspepsia; Abdominal Pain; Postprandial Period
PubMed: 38692696
DOI: 10.3949/ccjm.91a.23062 -
American Journal of Physiology. Cell... Jun 2024We recently demonstrated that acute oral ketone monoester intake induces a stimulation of postprandial myofibrillar protein synthesis rates comparable to that elicited... (Randomized Controlled Trial)
Randomized Controlled Trial
We recently demonstrated that acute oral ketone monoester intake induces a stimulation of postprandial myofibrillar protein synthesis rates comparable to that elicited following the ingestion of 10 g whey protein or their coingestion. The present investigation aimed to determine the acute effects of ingesting a ketone monoester, whey protein, or their coingestion on mechanistic target of rapamycin (mTOR)-related protein-protein colocalization and intracellular trafficking in human skeletal muscle. In a randomized, double-blind, parallel group design, 36 healthy recreationally active young males (age: 24.2 ± 4.1 yr) ingested either: ) 0.36 g·kg bodyweight of the ketone monoester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KET), ) 10 g whey protein (PRO), or ) the combination of both (KET + PRO). Muscle biopsies were obtained in the overnight postabsorptive state (basal conditions), and at 120 and 300 min in the postprandial period for immunofluorescence assessment of protein translocation and colocalization of mTOR-related signaling molecules. All treatments resulted in a significant (Interaction: < 0.0001) decrease in tuberous sclerosis complex 2 (TSC2)-Ras homolog enriched in brain (Rheb) colocalization at 120 min versus basal; however, the decrease was sustained at 300 min versus basal ( < 0.0001) only in KET + PRO. PRO and KET + PRO increased (Interaction: < 0.0001) mTOR-Rheb colocalization at 120 min versus basal; however, KET + PRO resulted in a sustained increase in mTOR-Rheb colocalization at 300 min that was greater than KET and PRO. Treatment intake increased mTOR-wheat germ agglutinin (WGA) colocalization at 120 and 300 min (Time: = 0.0031), suggesting translocation toward the fiber periphery. These findings demonstrate that ketone monoester intake can influence the spatial mechanisms involved in the regulation of mTORC1 in human skeletal muscle. We explored the effects of a ketone monoester (KET), whey protein (PRO), or their coingestion (KET + PRO) on mTOR-related protein-protein colocalization and intracellular trafficking in human muscle. All treatments decreased TSC2-Rheb colocalization at 120 minutes; however, KET + PRO sustained the decrease at 300 min. Only PRO and KET + PRO increased mTOR-Rheb colocalization; however, the increase at 300 min was greater in KET + PRO. Treatment intake increased mTOR-WGA colocalization, suggesting translocation to the fiber periphery. Ketone bodies influence the spatial regulation of mTOR.
Topics: Humans; Whey Proteins; Male; TOR Serine-Threonine Kinases; Young Adult; Adult; Muscle, Skeletal; Protein Transport; Double-Blind Method; 3-Hydroxybutyric Acid; Postprandial Period; Ketones; Muscle Proteins
PubMed: 38682238
DOI: 10.1152/ajpcell.00207.2024