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1.
Gan To Kagaku Ryoho ; 47(1): 156-158, 2020 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-32381890

RESUMO

PURPOSE: Perforated marginal ulcer after pancreaticoduodenectomy(PD)is a delayed complication. We evaluated the characteristics of the patients presenting perforated marginal ulcer after PD. METHODS: Five cases of perforated marginal ulcer after PD were reported at our hospital between 2008 and 2018, and the characteristics of these patients were evaluated. RESULTS: All 5 patients(4 females)with median age 73 years underwent subtotal stomach-preserving PD(SSPPD). In spite of the administration of gastric antisecretory medication, perforated marginal ulcer occurred in 3 patients(60%). All patients were treated with direct suture and omentum patch, and no mortality was reported. CONCLUSIONS: The perforating marginal ulcer after SSPPD occurred despite the administration of the gastric antisecretory medication. Treatment with direct suture and omentum patch was effective in perforated marginal ulcer after SSPPD.


Assuntos
Pancreaticoduodenectomia , Úlcera Péptica , Idoso , Feminino , Esvaziamento Gástrico , Humanos , Masculino , Pancreatectomia , Pancreaticoduodenectomia/efeitos adversos , Úlcera Péptica/etiologia
2.
Med Sci Monit ; 26: e919815, 2020 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-32248203

RESUMO

BACKGROUND Fructus aurantii is a flavonoid derived from Citrus aurantium (bitter orange) that is used in traditional Chinese medicine (TCM) to treat gastric motility disorders. This study aimed to investigate the effects of low-dose and high-dose decoctions of Fructus aurantii in a rat model of functional dyspepsia (FD). MATERIAL AND METHODS Sprague-Dawley rats (n=90) were divided into nine study groups: the control group, the FD model group, the domperidone-treated (Domp) group, the low-dose raw Fructus aurantii (FA-L) group, the high-dose raw Fructus aurantii (FA-H) group, the low-dose Fructus aurantii with stir-fried wheat bran (Bran-L) group, the high-dose Fructus aurantii with stir-fried wheat bran (Bran-H) group, the low-dose Fructus aurantii with stir-fried wheat bran and honey (Honey-L) group, and the high-dose Fructus aurantii with stir-fried wheat bran and honey (Honey-H) group. The FD rat model was established by semi-starvation, followed by tail damping, stimulation, and forced exercise with fatigue. Change in weight, rate of gastric emptying and intestinal propulsion, and serum levels of leptin, motilin, vasoactive intestinal peptide (VIP), gastrin, calcitonin gene-related peptide (CGRP), ghrelin, and cholecystokinin were compared between the groups. RESULTS In the FD model group, weight, rate of gastric emptying and intestinal propulsion significantly decreased, the expression of leptin, VIP and CGRP increased, and expression of motilin, gastrin, ghrelin, and cholecystokinin significantly decreased. Treatment with low-dose Fructus aurantii with stir-fried wheat bran significantly reversed these effects. CONCLUSIONS In the rat model of FD, low-dose Fructus aurantii with stir-fried wheat bran increased gastrointestinal motility and gastrointestinal hormone levels.


Assuntos
Citrus/química , Dispepsia/tratamento farmacológico , Animais , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/farmacologia , Esvaziamento Gástrico/efeitos dos fármacos , Esvaziamento Gástrico/fisiologia , Motilidade Gastrointestinal/efeitos dos fármacos , Motilidade Gastrointestinal/fisiologia , Medicina Tradicional Chinesa , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
3.
Zhongguo Zhen Jiu ; 40(4): 361-4, 2020 Apr 12.
Artigo em Chinês | MEDLINE | ID: mdl-32275362

RESUMO

OBJECTIVE: To explore the clinical therapeutic effect of herb-partitioned moxibustion at fanwei point in patients of diabetic gastroparesis differentiated as spleen and stomach deficiency and retention of turbid dampness as well as its effect mechanism. METHODS: A total of 134 patients with diabetic gastroparesis were randomized into an observation group and a control group, 67 cases in each one. In the observation group, herb-partitioned moxibustion at fanwei point was adopted, 40 min each time, once a day for 5 times a week. In the control group, itopride hydrochloride tablets were prescribed for oral administration, 50 mg each time, three times a day. A total of 6 weeks of treatment was required in the two groups. Before and after treatment, the gastroparesis cardinal symptom index (GCSI) scores, 4-hour gastric emptying rate, TCM symptom score, as well as the levels of plasma motilin and serum gastrin were observed in the patients of the two groups. Additionally, the clinical therapeutic effect was evaluated in the two groups. RESULTS: After treatment, the score of every item of GCSI, TCM symptom scores and the levels of plasma motilin and serum gastrin were all reduced as compared with those before treatment in the patients of the two groups (P<0.05), and those in the observation group were lower than the control group (P<0.05). Regarding 4-hour gastric emptying rates, which were increased as compared with those before treatment in the two group (P<0.05), and the rate in the observation group was higher remarkably than that in the control group (P<0.05). The total effective rate was 92.5% (62/67) in the observation group, higher than 74.6% (50/67) in the control group (P<0.05). CONCLUSION: Herb-partitioned moxibustion at fanwei point relieves the clinical symptoms in the patients with diabetic gastroparesis and increases the gastric emptying rate, which is probably related to the regulation of the levels of plasma motilin and serum gastrin.


Assuntos
Diabetes Mellitus , Gastrinas/sangue , Gastroparesia/terapia , Motilina/sangue , Moxibustão , Pontos de Acupuntura , Esvaziamento Gástrico , Humanos
4.
Food Chem ; 319: 126514, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32179369

RESUMO

Caseins and whey proteins are known as 'slow' and 'fast' proteins, respectively, based on their amino acid absorption rate. However, there is limited understanding of the mechanisms controlling their behaviour during gastro-intestinal transit. A protein model system (8% total protein) with varying casein:whey protein ratios (0:100, 20:80, 50:50 and 80:20) were subjected to in vitro gastro-intestinal digestion using a semi-dynamic gastric model, a static intestinal model and an ex vivo absorption model (Ussing chambers). The casein-rich (≥50%) samples showed the formation of solid coagula that were persistent throughout gastric digestion, which caused a delay in nutrient emptying, slower digestion and leucine absorption kinetics. In contrast, whey proteins formed more soluble aggregates during the gastric phase, which led to faster gastric emptying, rapid intestinal hydrolysis, and higher and faster leucine absorption. This work shows the key role of the gastric restructuring for the overall digestive mechanism and kinetics of food, in particular proteins.


Assuntos
Caseínas/química , Lipídeos/química , Proteínas do Soro do Leite/química , Animais , Digestão , Feminino , Esvaziamento Gástrico , Hidrólise , Leucina/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estômago
5.
Am J Physiol Gastrointest Liver Physiol ; 318(4): G682-G693, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32003602

RESUMO

Postprandial dyslipidemia is a common feature of insulin-resistant states and contributes to increased cardiovascular disease risk. Recently, bile acids have been recognized beyond their emulsification properties as important signaling molecules that promote energy expenditure, improve insulin sensitivity, and lower fasting lipemia. Although bile acid receptors have become novel pharmaceutical targets, their effects on postprandial lipid metabolism remain unclear. Here, we investigated the potential role of bile acids in regulation of postprandial chylomicron production and triglyceride excursion. Healthy C57BL/6 mice were given an intraduodenal infusion of taurocholic acid (TA) under fat-loaded conditions, and circulating lipids were measured. Targeting of bile acid receptors was achieved with GW4064, a synthetic agonist to the farnesoid X receptor (FXR), and deoxycholic acid (DCA), an activator of the Takeda G-protein-coupled receptor 5. TA, GW4064, and DCA treatments all lowered postprandial lipemia. FXR agonism also reduced intestinal triglyceride content and activity of microsomal triglyceride transfer protein, involved in chylomicron assembly. Importantly, TA (but not DCA) effects were largely lost in FXR knockout mice. These bile acid effects are reminiscent of the antidiabetic hormone glucagon-like peptide-1 (GLP-1). Although the GLP-1 receptor agonist exendin-4 retained its ability to acutely lower postprandial lipemia during bile acid sequestration and FXR deficiency, it did raise hepatic expression of the rate-limiting enzyme for bile acid synthesis. Bile acid signaling may be an important mechanism of controlling dietary lipid absorption, and bile acid receptors may constitute novel targets for the treatment of postprandial dyslipidemia.NEW & NOTEWORTHY We present new data suggesting potentially important roles for bile acids in regulation of postprandial lipid metabolism. Specific bile acid species, particularly secondary bile acids, were found to markedly inhibit absorption of dietary lipid and reduce postprandial triglyceride excursion. These effects appear to be mediated via bile acid receptors, farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). Importantly, bile acid signaling may trigger glucagon-like peptide-1 (GLP-1) secretion, which may in turn mediate the marked inhibitory effects on dietary fat absorption.


Assuntos
Ácido Desoxicólico/farmacologia , Hiperlipidemias/tratamento farmacológico , Isoxazóis/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Período Pós-Prandial , Receptores Citoplasmáticos e Nucleares/agonistas , Animais , Ácidos e Sais Biliares/metabolismo , Ácidos e Sais Biliares/farmacologia , Colesterol 7-alfa-Hidroxilase/genética , Colesterol 7-alfa-Hidroxilase/metabolismo , Exenatida/farmacologia , Esvaziamento Gástrico/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Insulina/sangue , Mucosa Intestinal , Intestinos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptores Acoplados a Proteínas-G/agonistas , Ácido Taurocólico/farmacologia
6.
Am J Physiol Gastrointest Liver Physiol ; 318(4): G635-G645, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32036693

RESUMO

Abnormal gastric accommodation (GA) and gastric emptying contribute to pathophysiology in functional dyspepsia (FD). Secretin is a key regulator of GA in animal studies. Our aim was to study the effects of secretin on gastric motility, satiation, postprandial symptoms, and key hormones. We performed two double-blind, randomized, saline-controlled crossover trials in 10 healthy volunteers and 10 patients with FD by Rome IV criteria. We used measured GA (by validated SPECT method) after a 111In radiolabeled Ensure 300-mL meal and quantified gastric emptying for 30 min by scintigraphy. Satiation was measured by volume to fullness (VTF) and maximum tolerated volume (MTV) on an Ensure nutrient drink test and postprandial symptoms 30 min post-MTV. Fasting and postprandial GLP-1, GIP, and HPP were measured. The ages and sex distribution of healthy controls and patients with FD were similar. Compared with placebo, secretin delayed gastric emptying at 30 min in both health [-11% (-16, -4), P = 0.004]; and FD [-8% (-9, 0), P = 0.03]. Satiation (VTF and MTV), GA, and plasma levels of GLP-1, GIP, and HPP did not differ between treatment arms in health or FD. On ANCOVA analysis (adjusting for age and sex), secretin did not consistently increase postprandial symptoms in health or FD. Secretin delayed gastric emptying in both health and FD without significantly altering GA, VTF, or MTV or selected hormones. Thus, secretin receptor activation may provide a novel therapeutic mechanism for patients with FD and rapid gastric emptying.NEW & NOTEWORTHY The naturally occurring hormone secretin retards gastric emptying of solids without deleteriously affecting gastric accommodation, satiation, other upper gastrointestinal hormones, or postprandial symptoms. Given these findings, a subset of patients with rapid gastric emptying (e.g., the estimated 20% of patients with functional dyspepsia) could be candidates for treatments that stimulate a secretin receptor such as sacubitril, which inhibits neprilysin, an enzyme that degrades secretin.


Assuntos
Dispepsia/tratamento farmacológico , Esvaziamento Gástrico/efeitos dos fármacos , Secretina/farmacologia , Adulto , Estudos Cross-Over , Sacarose na Dieta , Método Duplo-Cego , Feminino , Alimentos Formulados , Humanos , Masculino , Refeições , Pessoa de Meia-Idade , Período Pós-Prandial , Saciação
8.
Am J Physiol Gastrointest Liver Physiol ; 318(1): G203-G209, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31682161

RESUMO

Our aim was to investigate the feasibility of measuring antral contractions and duodenal bolus propagation (DBP) during dynamic antral contraction scintigraphy (DACS) as an assessment of antro-pyloro-duodenal coordination (APDC). Gastric emptying scintigraphy (GES) with DACS was performed with Tc-99m sulfur colloid (SC) using increasing doses of 74 MBq (2 mCi) for 10 subjects, 185 MBq (5 mCi) for 11, and 370 MBq (10 mCi) for 11. DACS was performed for 10 min after static images at 0, 30, 60, 120, 180, and 240 min in anterior and right anterior oblique (RAO) projections. Best projection and lowest dose of Tc-99m SC were assessed visually. DBP were quantified utilizing duodenal activity peaks from a region of interest in the first portion of the duodenum. DBP was better visualized in the RAO projection than anterior projection and using 185 MBq (5 mCi) and 370 MBq (10 mCi) compared with 74 MBq (2 mCi). DBP showed infrequent and irregular bolus transfers from the antrum to the duodenum. Antral activity peaks at 60 min averaged 2.91 ± 0.66 per minute and duodenum bolus peaks 0.36 ± 0.18 per minute (ratio 0.36/2.91 = 0.12). DBP activity peaks can be measured during GES with DACS but requires a 185-MBq (5 mCi) dose of Tc-99m SC radiolabeled test meal for adequate DBP signal detection and is better imaged in RAO than anterior projection. DBPs over the first 60 min postmeal ingestion are infrequent with only 12% of the antral contractions propagating into the duodenum. This methodology appears promising to assess APDC.NEW & NOTEWORTHY This study shows that duodenal bolus propagations after meal ingestion can be measured during gastric emptying scintigraphy using dynamic scintigraphy. Duodenal bolus propagation over the first 60 min postmeal ingestion are infrequent with only 12% of the antral contractions propagating into the duodenum. This methodology appears promising to assess antropyloroduodenal coordination in patients with unexplained symptoms of upper gastrointestinal dysmotility.


Assuntos
Duodeno/diagnóstico por imagem , Duodeno/fisiologia , Esvaziamento Gástrico , Trânsito Gastrointestinal , Antro Pilórico/diagnóstico por imagem , Antro Pilórico/fisiologia , Cintilografia , Compostos Radiofarmacêuticos/administração & dosagem , Coloide de Enxofre Marcado com Tecnécio Tc 99m/administração & dosagem , Adulto , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Tempo , Adulto Jovem
9.
J Laparoendosc Adv Surg Tech A ; 30(1): 31-35, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31539302

RESUMO

Background: Roux-en-Y gastric bypass (RYGB) is frequently performed for weight loss purposes in the morbidly obese population. The popularity and acceptance of this procedure have increased the knowledge of the physiological (anatomical and functional) changes that this technique produces in the organism. RYGB improves gastric emptying and gastroesophageal reflux symptoms. Materials and Methods: We analyzed 6 patients in whom an RYGB was performed for non-bariatric purposes. Symptom questionnaire was used to evaluate response. Results: None of the patients qualified for bariatric surgery, as all had a body mass index (BMI) <35 kg/m2. Five patients were operated on for severe gastroesophageal reflux disease symptoms, and one for gastroparesis. All patients had good to excellent results, with marginal modification of their BMI. Conclusion: Non-bariatric RYGB can be considered in patients with functional diseases of the upper gastrointestinal tract, regardless of their BMI.


Assuntos
Derivação Gástrica , Refluxo Gastroesofágico/cirurgia , Gastroparesia/cirurgia , Adolescente , Adulto , Índice de Massa Corporal , Feminino , Esvaziamento Gástrico , Gastroparesia/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Perda de Peso
10.
Gastroenterology ; 158(3): 506-514.e2, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31647902

RESUMO

BACKGROUND & AIMS: There have been conflicting results from trials of gastric electrical stimulation (GES) for treatment of refractory vomiting, associated or not with gastroparesis. We performed a large, multicenter, randomized, double-blind trial with crossover to study the efficacy of GES in patients with refractory vomiting, with or without gastroparesis. METHODS: For 4 months, we assessed symptoms in 172 patients (66% women; mean age ± standard deviation, 45 ± 12 years; 133 with gastroparesis) with chronic (>12 months) of refractory vomiting (idiopathic, associated with a type 1 or 2 diabetes, or postsurgical). A GES device was implanted and left unactivated until patients were randomly assigned, in a double-blind manner, to groups that received 4 months of stimulation parameters (14 Hz, 5 mA, pulses of 330 µs) or no stimulation (control); 149 patients then crossed over to the other group for 4 months. Patients were examined at the end of each 4-month period (at 5 and 9 months after implantation). Primary endpoints were vomiting score, ranging from 0 (daily vomiting) to 4 (no vomiting), and the quality of life, assessed by the Gastrointestinal Quality of Life Index scoring system. Secondary endpoints were changes in other digestive symptoms, nutritional status, gastric emptying, and control of diabetes. RESULTS: During both phases of the crossover study, vomiting scores were higher in the group with the device on (median score, 2) than the control group (median score, 1; P < .001), in diabetic and nondiabetic patients. Vomiting scores increased significantly when the device was ON in patients with delayed (P < .01) or normal gastric emptying (P = .05). Gastric emptying was not accelerated during the ON period compared with the OFF period. Having the GES turned on was not associated with increased quality of life. CONCLUSIONS: In a randomized crossover study, we found that GES reduced the frequency of refractory vomiting in patients with and without diabetes, although it did not accelerate gastric emptying or increase of quality of life. Clinicaltrials.gov, Number: NCT00903799.


Assuntos
Terapia por Estimulação Elétrica/métodos , Gastroparesia/complicações , Vômito/terapia , Adulto , Estudos Cross-Over , Método Duplo-Cego , Terapia por Estimulação Elétrica/instrumentação , Eletrodos Implantados , Feminino , Esvaziamento Gástrico/fisiologia , Gastroparesia/fisiopatologia , Gastroparesia/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Índice de Gravidade de Doença , Resultado do Tratamento , Vômito/diagnóstico , Vômito/etiologia
11.
Anaesthesia ; 75(3): 323-330, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31802485

RESUMO

We aimed to compare the reliability of aspiration via a nasogastric tube with ultrasound for assessment of residual gastric volume. Sixty-one adult patients who were mechanically ventilated and received continuous enteral feeding through a nasogastric tube for > 48 h were included. A first qualitative and quantitative ultrasound examination of the gastric antrum was followed by gastric suctioning, performed by an operator blinded to the result of the ultrasound examination. A second ultrasound examination was performed thereafter, followed by re-injection of the aspirated gastric contents (≤ 250 ml) into the stomach. A third ultrasound assessment was then immediately performed. If the suctioned volume was ≥ 250 ml, 250 mg erythromycin was infused over 30 min. A fourth ultrasound was performed 90 min after the third. Sixty (98%) patients had a qualitatively assessed full stomach at first ultrasound examination vs. 52 (85%) after gastric suctioning (p = 0.016). The calculated gastric volume significantly decreased after gastric suctioning, without a significant decrease in the number of patients with volume ≥ 250 ml. Four of the nine patients with calculated gastric volume ≥ 250 ml had vomiting within the last 24 h (p = 0.013). The antral cross-sectional area significantly decreased between the third and the fourth ultrasound examination (p = 0.015). Erythromycin infusion did not make a significant difference to gastric volume (n = 10). Our results demonstrate that gastric suctioning is not a reliable tool for monitoring residual gastric volume. Gastric ultrasound is a feasible and promising tool for gastric volume monitoring in clinical practice.


Assuntos
Aspiração Respiratória de Conteúdos Gástricos/diagnóstico por imagem , Estômago/diagnóstico por imagem , Sucção/métodos , Adulto , Idoso , Antibacterianos/efeitos adversos , Estudos de Coortes , Eritromicina/efeitos adversos , Feminino , Esvaziamento Gástrico , Conteúdo Gastrointestinal , Humanos , Intubação Gastrointestinal , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Estudos Prospectivos , Reprodutibilidade dos Testes , Estômago/anatomia & histologia , Estômago/efeitos dos fármacos , Ultrassonografia , Vômito/etiologia
12.
Am J Physiol Regul Integr Comp Physiol ; 318(2): R263-R273, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31774306

RESUMO

The rate of gastric emptying and the release of gastrointestinal (GI) hormones are major determinants of postprandial blood-glucose concentrations and energy intake. Preclinical studies suggest that activation of GI bitter-taste receptors potently stimulates GI hormones, including glucagon-like peptide-1 (GLP-1), and thus may reduce postprandial glucose and energy intake. We evaluated the effects of intragastric quinine on the glycemic response to, and the gastric emptying of, a mixed-nutrient drink and the effects on subsequent energy intake in healthy men. The study consisted of 2 parts: part A included 15 lean men, and part B included 12 lean men (aged 26 ± 2 yr). In each part, participants received, on 3 separate occasions, in double-blind, randomized fashion, intragastric quinine (275 or 600 mg) or control, 30 min before a mixed-nutrient drink (part A) or before a buffet meal (part B). In part A, plasma glucose, insulin, glucagon, and GLP-1 concentrations were measured at baseline, after quinine alone, and for 2 h following the drink. Gastric emptying of the drink was also measured. In part B, energy intake at the buffet meal was quantified. Quinine in 600 mg (Q600) and 275 mg (Q275) doses alone stimulated insulin modestly (P < 0.05). After the drink, Q600 and Q275 reduced plasma glucose and stimulated insulin (P < 0.05), Q275 stimulated GLP-1 (P < 0.05), and Q600 tended to stimulate GLP-1 (P = 0.066) and glucagon (P = 0.073) compared with control. Quinine did not affect gastric emptying of the drink or energy intake. In conclusion, in healthy men, intragastric quinine reduces postprandial blood glucose and stimulates insulin and GLP-1 but does not slow gastric emptying or reduce energy intake under our experimental conditions.


Assuntos
Bebidas , Glicemia/efeitos dos fármacos , Alimentos Formulados , Esvaziamento Gástrico/efeitos dos fármacos , Hipoglicemiantes/administração & dosagem , Quinina/administração & dosagem , Paladar/efeitos dos fármacos , Adulto , Biomarcadores/sangue , Glicemia/metabolismo , Método Duplo-Cego , Ingestão de Energia , Glucagon/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Voluntários Saudáveis , Humanos , Insulina/sangue , Masculino , Período Pós-Prandial , Fatores de Tempo , Adulto Jovem
13.
Diabetes Res Clin Pract ; 159: 107951, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31790715

RESUMO

AIMS: Gastric emptying is a major determinant of postprandial glycaemia in both health and type 2 diabetes (T2DM); the potential impact of ethnicity on gastric emptying is unclear. We compared the rate of gastric emptying of a standardised meal and the associated glycaemic response in Han Chinese and Caucasian patients with T2DM. METHODS: 14 Han Chinese and 14 Caucasian T2DM patients, managed by diet and/or metformin monotherapy, underwent concurrent measurements of gastric emptying and blood glucose for 240 min after a 99mTc-calcium phytate-labelled mashed potato meal. RESULTS: Han Chinese patients were slightly younger (P < 0.05), and had a lower BMI (P < 0.05), than Caucasians. There were no differences in either HbA1c or fasting blood glucose between them. Gastric half-emptying time (T50) was shorter (P < 0.05) and the postprandial blood glucose increment greater (P < 0.05) in Han Chinese than Caucasian patients. Both the increment in blood glucose from baseline at 60 min and peak blood glucose were related inversely to T50 (P < 0.05 each). CONCLUSIONS: Han Chinese with relatively well-controlled T2DM have more rapid gastric emptying compared to Caucasians, which is associated with a greater postprandial glycaemic excursion. These differences may inform the choice of management, e.g. Han Chinese may particularly benefit from therapies that slow gastric emptying.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Esvaziamento Gástrico/fisiologia , Período Pós-Prandial/fisiologia , Adolescente , Adulto , Criança , Feminino , Disparidades em Assistência à Saúde , Humanos , Masculino , Adulto Jovem
14.
Gut ; 69(3): 591-600, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31784469

RESUMO

Emerging data increasingly point towards the duodenum as a key region underlying the pathophysiology of functional dyspepsia (FD), one of the most prevalent functional GI disorders. The duodenum plays a major role in the control and coordination of gastroduodenal function. Impaired duodenal mucosal integrity and low-grade inflammation have been associated with altered neuronal signalling and systemic immune activation, and these alterations may ultimately lead to dyspeptic symptoms. Likely luminal candidates inducing the duodenal barrier defect include acid, bile, the microbiota and food antigens although no causal association with symptoms has been convincingly demonstrated. Recognition of duodenal pathology in FD will hopefully lead to the discovery of new biomarkers and therapeutic targets, allowing biologically targeted rather than symptom-based therapy. In this review, we summarise the recent advances in the diagnosis and treatment of FD with a focus on the duodenum.


Assuntos
Duodeno/fisiopatologia , Dispepsia/tratamento farmacológico , Dispepsia/etiologia , Antibacterianos/uso terapêutico , Ácidos e Sais Biliares/metabolismo , Encéfalo/fisiopatologia , Duodeno/imunologia , Duodeno/metabolismo , Duodeno/microbiologia , Disbiose/tratamento farmacológico , Disbiose/fisiopatologia , Dispepsia/diagnóstico , Dispepsia/fisiopatologia , Esvaziamento Gástrico , Humanos , Neurotransmissores/uso terapêutico , Probióticos/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico
16.
AAPS J ; 22(1): 6, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31792743

RESUMO

In the present investigation, it was explored whether food effect on drug absorption in adults is similar with the food effect after administration of an infant meal with the drug product to adults. After confirming lack of pharmaceutical and pharmacokinetic interaction, a paracetamol suspension and an ibuprofen suspension were co-administered to eight healthy adults on a crossover basis in three different occasions, i.e. in the fasted state (as defined by regulatory agencies, fasted conditions), in the fed state (as defined by regulatory agencies, fed conditions) and under conditions simulating the fed state in infants (infant fed conditions). Unlike under fed conditions, under infant fed conditions early exposure was significantly lower than under fasted conditions for both paracetamol and ibuprofen. Also, for ibuprofen, Cmax values under infant fed conditions were significantly higher than under fed conditions. These data suggest that, even for drugs with non-problematic absorption administered in simple dosage forms, food effects in infants may not be adequately evaluated if the protocol suggested by regulatory agencies is applied. The usefulness of the methodology employed in the present investigation for simulating the fed state in infants deserves further evaluation. Until then, food effects in infants should be considered cautiously or be evaluated in infants.


Assuntos
Acetaminofen/farmacocinética , Analgésicos não Entorpecentes/farmacocinética , Interações Alimento-Droga , Ibuprofeno/farmacocinética , Fórmulas Infantis , Acetaminofen/sangue , Adulto , Analgésicos não Entorpecentes/sangue , Esvaziamento Gástrico , Voluntários Saudáveis , Humanos , Ibuprofeno/sangue , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
PLoS One ; 14(12): e0226065, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31805134

RESUMO

The objectives of this study were to assess gastrointestinal transit times, sedation, and signs of nausea associated with intravenous lidocaine infusions in dogs following targeted acupuncture at Pericardium-6 (PC6) and Stomach-36 (ST36). In a randomized, blind crossover design, 6 healthy, adult Beagles were fed thirty 1.5 mm barium-impregnated polyethylene spheres (BIPS), then were subject to 30 minutes of: 1) no acupuncture, 2) bilateral targeted acupuncture at PC6 and ST36, or 3) bilateral non-target acupuncture at Lung-5 (LU5) and Bladder-55 (BL55). Lidocaine was immediately administered at 1 mg/kg intravenously followed by 50 µg/kg/min. BIPS were tracked radiographically; sedation and nausea were scored at baseline (Time 0) and for 11 hours during lidocaine infusions. Transit times and sedation and nausea scores were analyzed with a linear mixed-effects model; the number of BIPS at defined time points was analyzed with a piecewise linear mixed-effects model. All P values were two-sided and P < 0.05 was considered significant. Sedation and nausea scores did not differ between treatments at any time point (all P > 0.05). However, nausea scores in all groups were significantly greater at Times 5 through 7 and at Time 11 compared to Time 0 whereas sedation scores in all groups were significantly greater at Times 2 through 11 compared to Time 0 (all P < 0.05). The number of BIPs found out of the stomach, the number found in the large intestine, gastric emptying and gastrointestinal transit times did not differ between treatments (all P > 0.05). Acupuncture at PC6 and ST36 did not alleviate nausea and sedation associated with lidocaine infusions in clinically normal animals or affect gastric emptying and gastrointestinal transit.


Assuntos
Pontos de Acupuntura , Terapia por Acupuntura , Sedação Consciente , Motilidade Gastrointestinal/efeitos dos fármacos , Lidocaína/administração & dosagem , Lidocaína/efeitos adversos , Náusea/induzido quimicamente , Animais , Cães , Feminino , Esvaziamento Gástrico/efeitos dos fármacos , Infusões Intravenosas , Masculino , Náusea/diagnóstico por imagem , Náusea/prevenção & controle , Radiografia
18.
Diabetes Res Clin Pract ; 158: 107892, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31669625

RESUMO

AIMS: Glucagon has an important role in glucose homeostasis. Recently, a new plasma glucagon assay based on liquid chromatography-high resolution mass spectrometry was developed. We evaluated the influence of a dipeptidyl peptidase-4 inhibitor (anagliptin) on plasma glucagon levels in Japanese patients with type 2 diabetes by using this new assay. METHODS: Twenty-four patients with type 2 diabetes were enrolled in a prospective, single-center, randomized, open-label study and were randomly allocated to 4 weeks of treatment with metformin (1000 mg/day) or anagliptin (200 mg/day). A liquid test meal labeled with sodium [13C] acetate was ingested before and after the treatment period. Samples of blood and expired air were collected over 3 h. Plasma levels of glucose, glucagon, C-peptide, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were measured, and gastric emptying was also evaluated. RESULTS: Twenty-two patients completed the study (metformin group: n = 10; anagliptin group: n = 12). Glycemic control showed similar improvement in both groups. In the anagliptin group, there was a slight decrease of the incremental area under the plasma concentration versus time curve for glucagon after the test meal (P = 0.048). In addition, the plasma level of active GLP-1 and GIP was increased, and plasma C-peptide was also increased versus baseline. Neither anagliptin nor metformin delayed gastric emptying. CONCLUSIONS: In patients with type 2 diabetes maintained endogenous insulin secretion, anagliptin increased the plasma level of active GLP-1 and GIP in association with a slight stimulation of insulin secretion and slight inhibition of glucagon secretion, but did not delay gastric emptying. Clinical Trial Registry: University hospital Medical Information Network UMIN000028293.


Assuntos
Esvaziamento Gástrico/efeitos dos fármacos , Glucagon/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Espectrometria de Massas/métodos , Metformina/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Idoso , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Hipoglicemiantes/farmacologia , Masculino , Metformina/farmacologia , Pessoa de Meia-Idade , Estudos Prospectivos , Pirimidinas/farmacologia , Adulto Jovem
19.
Nutrients ; 11(11)2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31694157

RESUMO

A whey protein/guar gum preload reduces postprandial glycaemia in type 2 diabetes through slowing gastric emptying. However, gastric emptying has previously been assessed using a stable isotope breath test technique, which cannot discriminate between slowing of gastric emptying and small intestinal absorption. This preload also may be useful in the management of postprandial hypotension. We evaluated the effects of a whey protein/guar preload on gastric emptying, glucose absorption, glycaemic/insulinaemic and blood pressure (BP) responses to an oral glucose load. Eighteen healthy older participants underwent measurements of gastric emptying (scintigraphy), plasma glucose and insulin, glucose absorption, superior mesenteric artery (SMA) flow, BP and heart rate (HR) after ingesting a 50 g glucose drink, with or without the preload. The preload reduced plasma glucose (p = 0.02) and serum 3-O-methylglucose (3-OMG) (p = 0.003), and increased plasma insulin (p = 0.03). There was no difference in gastric emptying or BP between the two days. The reduction in plasma glucose on the preload day was related to the reduction in glucose absorption (r = 0.71, p = 0.002). In conclusion, the glucose-lowering effect of the preload may relate to delayed small intestinal glucose absorption and insulin stimulation, rather than slowing of gastric emptying.


Assuntos
Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Galactanos/farmacologia , Esvaziamento Gástrico/efeitos dos fármacos , Absorção Intestinal/efeitos dos fármacos , Mananas/farmacologia , Gomas Vegetais/farmacologia , Proteínas do Soro do Leite/farmacologia , 3-O-Metilglucose/sangue , Idoso , Feminino , Voluntários Saudáveis , Frequência Cardíaca/efeitos dos fármacos , Humanos , Insulina/sangue , Intestino Delgado/metabolismo , Masculino , Período Pós-Prandial/efeitos dos fármacos
20.
Int J Pharm ; 572: 118783, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31678393

RESUMO

The purpose of this study was to develop a novel gastroretentive drug delivery system with immediate buoyancy and high wet strength. The proposed bilayer tablet was composed of a drug layer and a highly porous and swellable gastroretentive (GR) layer. The highly porous GR layer was prepared by sublimating the volatile materials after compaction with swellable polymers. This pore-forming process decreased the density of the GR layer and enabled the tablet to float immediately on the dissolution media. The GR layer formulation was optimized by comparing the swelling, erosion, and mechanical properties of candidate swellable polymers. The release rates were conveniently controlled by changing the polymer content in the drug layer, while the swelling and floating properties were provided by the GR layer. The application of percolation theory revealed that the polymer content above the estimated threshold was required for a reliable drug release profile. In vivo study in fed beagle dogs confirmed the enhanced gastric retention time of the tablets compared to that of conventional single layer tablets. Taken together, our data suggest that the proposed system can be a promising platform technology with superior GR properties and a convenient formulation process.


Assuntos
Portadores de Fármacos , Antagonistas dos Receptores Histamínicos H2/administração & dosagem , Polímeros/química , Ranitidina/administração & dosagem , Administração Oral , Animais , Cães , Composição de Medicamentos , Liberação Controlada de Fármacos , Absorção Gástrica , Esvaziamento Gástrico , Antagonistas dos Receptores Histamínicos H2/química , Antagonistas dos Receptores Histamínicos H2/farmacocinética , Masculino , Porosidade , Período Pós-Prandial , Ranitidina/química , Ranitidina/farmacocinética , Solubilidade , Comprimidos
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