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1.
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
2.
Am J Physiol Regul Integr Comp Physiol ; 318(4): R790-R798, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32160019

RESUMO

The fatty acid, lauric acid (C12), and the amino acid, leucine (Leu) stimulate gut hormones, including CCK, associated with suppression of energy intake. In our recent study, intraduodenal infusion of a combination of C12 and l-tryptophan, at loads that individually did not affect energy intake, reduced energy intake substantially, associated with much greater stimulation of CCK. We have now investigated whether combined administration of C12 and Leu would enhance the intake-suppressant effects of each nutrient, when given at loads that each suppress energy intake individually. Sixteen healthy, lean males (age: 23 ± 2 yr) received, in randomized, double-blind fashion, 90-min intraduodenal infusions of control (saline), C12 (0.4 kcal/min), Leu (0.45 kcal/min), or C12+Leu (0.85 kcal/min). Antropyloroduodenal pressures were measured continuously and plasma CCK at 15-min intervals, and energy intake from a standardized buffet-meal, consumed immediately postinfusion, was quantified. All nutrient infusions stimulated plasma CCK compared with control (P < 0.05). Moreover, C12 and C12+Leu stimulated CCK compared with Leu (P < 0.05) (mean concentration, pmol/L; control: 2.3 ± 0.3, C12: 3.8 ± 0.3, Leu: 2.7 ± 0.3, and C12+Leu: 4.0 ± 0.4). C12+Leu, but not C12 or Leu, stimulated pyloric pressures (P < 0.05). C12+Leu and C12 reduced energy intake (P < 0.05), and there was a trend for Leu to reduce (P = 0.06) energy intake compared with control, with no differences between the three nutrient treatments (kcal; control: 1398 ± 84, C12: 1226 ± 80, Leu: 1260 ± 92, and C12+Leu: 1208 ± 83). In conclusion, combination of C12 and Leu, at the loads given, did not reduce energy intake beyond their individual effects, possibly because maximal effects had been evoked.


Assuntos
Colecistocinina/sangue , Ingestão de Energia , Motilidade Gastrointestinal/efeitos dos fármacos , Ácidos Láuricos/farmacologia , Leucina/farmacologia , Adolescente , Adulto , Apetite/efeitos dos fármacos , Método Duplo-Cego , Ingestão de Alimentos/efeitos dos fármacos , Humanos , Ácidos Láuricos/administração & dosagem , Leucina/administração & dosagem , Masculino , Adulto Jovem
3.
Zhonghua Nei Ke Za Zhi ; 59(2): 117-123, 2020 Feb 01.
Artigo em Chinês | MEDLINE | ID: mdl-32074684

RESUMO

Objective: To evaluate the efficacy and safety of Oryz-Aspergillus enzyme and pancreatin tablets (Combizym(®)) in the treatment of postprandial distress syndrome (PDS) in the elderly, compared with gastrointestinal motility drugs. Methods: A prospective randomized controlled trial was designed and registered in the China Clinical Trials Registry (ChiCTR-IPR-16008185). The elderly patients with PDS were randomly divided into three groups, including Mosapride group with Mosapride citrate tablets 5 mg 3 times per day for 2 weeks; Combizym(®) group with Combizym tablets 244 mg 3 times per day for 2 weeks; combined treatment group with both drugs and same doses for 2 weeks. The modified Nepean dyspepsia index (NDSI) score, discomfort intensity score and PDS score were calculated on patients before treatment, at the end of first and second week of treatment, as well as 4 weeks after treatment finished, respectively. Adverse effects were evaluated. Results: A total of 323 patients from 16 tertiary hospitals in China were enrolled in this study. Among them, 105 patients were in Mosapride group, 109 in Combizym(®) group and 109 in combined treatment group. There were 148 males (45.8%) and 175 females (54.2%) with median age 71.4±9.0 years (60-100 years). Baseline characteristics of three groups were comparable. After treatment, the NDSI scores in three groups all decreased significantly (P<0.001), while they were similar between groups (P>0.05). The discomfort intensity score and PDS score in three groups showed a significant reduction after treatment (P<0.001), especially in the combined treatment group. Compared with Mosapride group, the scores in Combizym(®) group decreased significantly after one or two weeks [discomfort intensity score: after one week, 4.0(2.5, 8.0) vs. 6.0(3.0, 10.0); after two weeks, 3.0(0.0, 5.0) vs. 4.0(2.0, 6.0); all P<0.05. PDS score: after one week, 6.0(3.0, 9.0) vs. 7.0(3.5, 10.5); after two weeks, 3.0(0.0, 5.0) vs. 4.0(2.0, 7.0); all P<0.05]. The efficacy rate in all patients after first week of treatment was over 15.0%. The efficacy rates after two weeks were 55.2%, 68.8% and 73.4% in Mosapride group, Combizym(®) group and combined treatment group, respectively. After two week treatment, the efficacy rates in Combizym(®) group (P=0.041) and combined group (P=0.006) were higher than that of Mosapride group. The recurrence rate of Mosapride group was 9.5%, which was significantly higher than that of Combizym(®) group (1.8%, P<0.05) and combined treatment group (1.8%, P<0.05). There were no serious adverse effects in the three groups. Conclusions: The efficacy of Oryz-Aspergillus enzyme and pancreatin tablets is comparable with that of Mosapride in elderly PDS patients, with fewer adverse effects and low recurrence rate. Combination regimen indicates better efficacy than that of Oryz-Aspergillus enzyme and pancreatin tablets or Mosapride alone.


Assuntos
Benzamidas/uso terapêutico , Dispepsia/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Motilidade Gastrointestinal/efeitos dos fármacos , Glicosídeo Hidrolases/uso terapêutico , Morfolinas/uso terapêutico , Pancreatina/uso terapêutico , Peptídeo Hidrolases/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , Benzamidas/efeitos adversos , China , Combinação de Medicamentos , Dispepsia/diagnóstico , Dispepsia/patologia , Feminino , Fármacos Gastrointestinais/efeitos adversos , Glicosídeo Hidrolases/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Morfolinas/efeitos adversos , Pancreatina/efeitos adversos , Peptídeo Hidrolases/efeitos adversos , Período Pós-Prandial , Estudos Prospectivos , Resultado do Tratamento
4.
Gastroenterology ; 158(5): 1232-1249.e3, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31945360

RESUMO

With a worldwide prevalence of 15%, chronic constipation is one of the most frequent gastrointestinal diagnoses made in ambulatory medicine clinics, and is a common source cause for referrals to gastroenterologists and colorectal surgeons in the United States. Symptoms vary among patients; straining, incomplete evacuation, and a sense of anorectal blockage are just as important as decreased stool frequency. Chronic constipation is either a primary disorder (such as normal transit, slow transit, or defecatory disorders) or a secondary one (due to medications or, in rare cases, anatomic alterations). Colonic sensorimotor disturbances and pelvic floor dysfunction (such as defecatory disorders) are the most widely recognized pathogenic mechanisms. Guided by efficacy and cost, management of constipation should begin with dietary fiber supplementation and stimulant and/or osmotic laxatives, as appropriate, followed, if necessary, by intestinal secretagogues and/or prokinetic agents. Peripherally acting µ-opiate antagonists are another option for opioid-induced constipation. Anorectal tests to evaluate for defecatory disorders should be performed in patients who do not respond to over-the-counter agents. Colonic transit, followed if necessary with assessment of colonic motility with manometry and/or a barostat, can identify colonic dysmotility. Defecatory disorders often respond to biofeedback therapy. For specific patients, slow-transit constipation may necessitate a colectomy. No studies have compared inexpensive laxatives with newer drugs with different mechanisms. We review the mechanisms, evaluation, and management of chronic constipation. We discuss the importance of meticulous analyses of patient history and physical examination, advantages and disadvantages of diagnostic testing, guidance for individualized treatment, and management of medically refractory patients.


Assuntos
Constipação Intestinal/terapia , Defecação/fisiologia , Motilidade Gastrointestinal/fisiologia , Doença Crônica/epidemiologia , Doença Crônica/terapia , Colo/diagnóstico por imagem , Colo/inervação , Colo/metabolismo , Colo/fisiopatologia , Constipação Intestinal/diagnóstico , Constipação Intestinal/epidemiologia , Constipação Intestinal/etiologia , Defecografia , Fibras na Dieta/administração & dosagem , Suplementos Nutricionais , Exame Retal Digital , Eletromiografia , Motilidade Gastrointestinal/efeitos dos fármacos , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/fisiopatologia , Laxantes/administração & dosagem , Imagem por Ressonância Magnética , Manometria , Diafragma da Pelve/inervação , Diafragma da Pelve/fisiopatologia , Prevalência , Receptores Opioides mu/antagonistas & inibidores , Receptores Opioides mu/metabolismo , Reto/diagnóstico por imagem , Reto/inervação , Reto/metabolismo , Reto/fisiopatologia , Secretagogos/administração & dosagem
5.
PLoS One ; 15(1): e0227781, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31978146

RESUMO

BACKGROUND: Memantine, currently available for the treatment of Alzheimer's disease, is an uncompetitive antagonist of the N-methyl-D-aspartate type of glutamate receptors. Under normal physiologic conditions, these unstimulated receptor ion channels are blocked by magnesium ions, which are displaced after agonist-induced depolarization. In humans, memantine administration is associated with different gastrointestinal dysmotility side effects (vomiting, diarrhoea, constipation, motor-mediated abdominal pain), thus limiting its clinical use. Mechanism of these motility disorders has not been clarified yet. Pigs can be used in various preclinical experiments due to their relatively very similar gastrointestinal functions compared to humans. The aim of this study was to evaluate the impact of a single and repeated doses of memantine on porcine gastric myoelectric activity evaluated by means of electrogastrography (EGG). METHODS: Six adult female experimental pigs (Sus scrofa f. domestica, mean weight 41.7±5.0 kg) entered the study for two times. The first EGG was recorded after a single intragastric dose of memantine (20 mg). In the second part, EGG was accomplished after 7-day intragastric administration (20 mg per day). All EGG recordings were performed under general anaesthesia. Basal (15 minutes) and study recordings (120 minutes) were accomplished using an EGG stand (MMS, Enschede, the Netherlands). Running spectral analysis based on Fourier transform was used. Results were expressed as dominant frequency of gastric slow waves (DF) and power analysis (areas of amplitudes). RESULTS: Single dose of memantine significantly increased DF, from basic values (1.65±1.05 cycles per min.) to 2.86 cpm after 30 min. (p = 0.008), lasting till 75 min. (p = 0.014). Basal power (median 452; inter-quartile range 280-1312 µV^2) raised after 15 min. (median 827; IQR 224-2769; p = 0.386; NS), lasting next 30 min. Repetitively administrated memantine caused important gastric arrhythmia. Basal DF after single and repeated administration was not different, however, a DF increase in the second part was more prominent (up to 3.18±2.16 after 15 and 30 min., p<0.001). In comparison with a single dose, basal power was significantly higher after repetitively administrated memantine (median 3940; IQR 695-15023 µV^2; p<0.001). Next dose of 20 mg memantine in the second part induced a prominent drop of power after 15 min. (median 541; IQR 328-2280 µV^2; p<0.001), lasting till 120 min. (p<0.001). CONCLUSIONS: Both single and repeated doses of memantine increased DF. Severe gastric arrhythmia and long-lasting low power after repeated administration might explain possible gastric dysmotility side effects in the chronic use of memantine.


Assuntos
Antagonistas de Aminoácidos Excitatórios/efeitos adversos , Gastroenteropatias/induzido quimicamente , Motilidade Gastrointestinal/efeitos dos fármacos , Memantina/efeitos adversos , Estômago/efeitos dos fármacos , Administração Oral , Doença de Alzheimer/tratamento farmacológico , Animais , Modelos Animais de Doenças , Eletromiografia , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Feminino , Gastroenteropatias/diagnóstico , Gastroenteropatias/fisiopatologia , Motilidade Gastrointestinal/fisiologia , Humanos , Memantina/administração & dosagem , Estômago/fisiopatologia , Sus scrofa
7.
J Ethnopharmacol ; 247: 112224, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31509779

RESUMO

ETHNO-PHARMACOLOGICAL RELEVANCE: Corchorus olitorius is reportedly used in ethno-medicine to arrest threatened miscarriage and other conditions associated with excessive uterine contractions. The plant is also used as a purgative, demulscent and an anti-inflammatory agent. AIM OF THE STUDY: Against the background of ethno-medicinal use, this current work was designed to evaluate the gastrointestinal and uterine smooth muscles relaxant and anti-inflammatory effects of Corchorus olitorius leaf extract (COLE). MATERIALS AND METHODS: Pieces of uterine and gastrointestinal tissues were suspended separately in organ baths containing ideal physiological salt solutions bubbled with air and were tested for responses to standard drugs and COLE, then repeated in the presence of antagonists. Anti-inflammatory study was carried out via the egg albumin-induced paw edema model in rats. RESULTS: The application of COLE to pieces of uterine tissue significantly decreased the amplitudes of contractions in a dose dependent manner such that the highest dose applied (666.67 µg/ml) achieved a 100% inhibitory effect. Oxytocin induced contractions were also significantly inhibited by both salbutamol and COLE. On the isolated rabbit jejunum, the effect of COLE was also inhibitory and like atropine, significantly inhibited acetylcholine induced contractions. In the in vivo study, the extract inhibited charcoal meal movement in test rats when compared with control. Anti-inflammatory effect of COLE was significant and compared favourably with that of aspirin following in vivo trials. CONCLUSIONS: COLE therefore, may be a good tocolytic, anti-diarrheal and anti-inflammatory agent and offers hope of new drug discovery for such uses.


Assuntos
Anti-Inflamatórios/farmacologia , Antidiarreicos/farmacologia , Corchorus/química , Extratos Vegetais/farmacologia , Tocolíticos/farmacologia , Aborto Espontâneo/prevenção & controle , Animais , Anti-Inflamatórios/isolamento & purificação , Antidiarreicos/isolamento & purificação , Aspirina/farmacologia , Diarreia/tratamento farmacológico , Modelos Animais de Doenças , Edema/tratamento farmacológico , Edema/imunologia , Etnofarmacologia , Feminino , Motilidade Gastrointestinal/efeitos dos fármacos , Jejuno/efeitos dos fármacos , Jejuno/fisiologia , Contração Muscular/efeitos dos fármacos , Miométrio/efeitos dos fármacos , Nigéria , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Gravidez , Coelhos , Ratos , Tocolíticos/isolamento & purificação
8.
Gen Comp Endocrinol ; 285: 113294, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31585115

RESUMO

Motilin and ghrelin were identified in the pheasant by molecular cloning, and the actions of both peptides on the contractility of gastrointestinal (GI) strips were examined in vitro. Molecular cloning indicated that the deduced amino acid sequences of the pheasant motilin and ghrelin were a 22-amino acid peptide, FVPFFTQSDIQKMQEKERIKGQ, and a 26-amino acid peptide, GSSFLSPAYKNIQQQKDTRKPTGRLH, respectively. In in vitro studies using pheasant GI strips, chicken motilin caused contraction of the proventriculus and small intestine, whereas the crop and colon were insensitive. Human motilin, but not erythromycin, caused contraction of small intestine. Chicken motilin-induced contractions in the proventriculus and ileum were not inhibited by a mammalian motilin receptor antagonist, GM109. Neither atropine (a cholinergic receptor antagonist) nor tetrodotoxin (a neuron blocker) inhibited the responses of chicken motilin in the ileum but both drugs decreased the responses to motilin in the proventriculus, suggesting that the contractile mechanisms of motilin in the proventriculus was neurogenic, different from that of the small intestine (myogenic). On the other hand, chicken and quail ghrelin did not cause contraction in any regions of pheasant GI tract. Since interaction of ghrelin and motilin has been reported in the house musk shrew, interaction of two peptides was examined. The chicken motilin-induced contractions were not modified by ghrelin, and ghrelin also did not cause any contraction under the presence of motilin, suggesting the absence of interaction in both peptides. In conclusion, both the motilin system and ghrelin system are present in the pheasant. Regulation of GI motility by motilin might be common in avian species. However, absence of ghrelin actions in any GI regions suggests the avian species-related difference in regulation of GI contractility by ghrelin.


Assuntos
Aves/metabolismo , Trato Gastrointestinal/fisiologia , Grelina/farmacologia , Motilina/farmacologia , Contração Muscular/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Atropina/farmacologia , Sequência de Bases , Galinhas , Clonagem Molecular , Feminino , Motilidade Gastrointestinal/efeitos dos fármacos , Motilidade Gastrointestinal/fisiologia , Trato Gastrointestinal/efeitos dos fármacos , Grelina/química , Grelina/genética , Humanos , Masculino , Motilina/química , Motilina/genética , Proventrículo/efeitos dos fármacos , Codorniz , Ratos , Receptores dos Hormônios Gastrointestinais/metabolismo , Receptores de Neuropeptídeos/metabolismo , Tetrodotoxina/farmacologia
9.
Curr Gastroenterol Rep ; 21(12): 69, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31823129

RESUMO

PURPOSE OF REVIEW: This paper seeks to highlight GI motility disorders that are frequently present in patients with a malignancy. GI dysmotility can occur due to the cancer itself or as a consequence of medical and surgical treatments. Often, symptoms are nonspecific and the diagnosis requires a high index of suspicion. The goal of the paper is to review the common motility problems seen in patients with cancer, their clinical manifestations, and options for management. RECENT FINDINGS: Studies show that newer endoscopy techniques such as endoscopic mucosal dissection can cause esophageal dysmotility. Opioid-induced constipation is frequently encountered in patients with cancer. Motility disorders in cancer patient can lead to clinical morbidity, poor quality of life, and malnutrition. Newer diagnostic tests and medical and surgical treatments may be helpful in improving the diagnosis and management of these disorders.


Assuntos
Analgésicos Opioides/efeitos adversos , Gastroenteropatias/fisiopatologia , Motilidade Gastrointestinal/fisiologia , Neoplasias , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/etiologia , Constipação Intestinal/terapia , Gastroenteropatias/diagnóstico , Gastroenteropatias/etiologia , Gastroenteropatias/terapia , Motilidade Gastrointestinal/efeitos dos fármacos , Motilidade Gastrointestinal/efeitos da radiação , Humanos , Neoplasias/fisiopatologia , Neoplasias/terapia , Síndromes Paraneoplásicas/etiologia , Síndromes Paraneoplásicas/fisiopatologia , Síndromes Paraneoplásicas/terapia
10.
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
11.
J Evid Based Integr Med ; 24: 2515690X19891952, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31840545

RESUMO

Traditionally people used Dodonaea viscosa for the treatment of various ailments, including diarrhea. Therefore, this study was aimed to evaluate the antidiarrheal activity of the 80% methanolic leaf extract of D viscosa against castor oil-induced diarrhea in mice models. Different doses of 80% methanolic leaf extract of D viscosa (100, 200, and 400 mg/kg) were evaluated for their antidiarrheal activities using castor oil-induced diarrhea, gastrointestinal transit, and enteropooling models in Swiss albino mice. At all test doses, the plant extract showed significant (P < .05) inhibition in the frequency of defecation of wet feces and total fecal output as compared to the control group. Similarly, at all dose ranges used the plant extract demonstrated significant (P < .05) reduction in an intraluminal fluid accumulation as compared to the untreated group. Besides, at higher doses, the plant extract also indicated significant (P < .05) antimotility activity in comparison with the control. In conclusion, these findings illustrated that the 80% methanolic leaf extract of D viscosa supported the traditional claim of antidiarrheal activity of the plant though further investigations are warranted.


Assuntos
Antidiarreicos/administração & dosagem , Diarreia/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Sapindaceae/química , Animais , Antidiarreicos/isolamento & purificação , Óleo de Rícino/efeitos adversos , Defecação/efeitos dos fármacos , Diarreia/induzido quimicamente , Diarreia/fisiopatologia , Avaliação Pré-Clínica de Medicamentos , Feminino , Motilidade Gastrointestinal/efeitos dos fármacos , Trânsito Gastrointestinal/efeitos dos fármacos , Humanos , Camundongos , Extratos Vegetais/isolamento & purificação
12.
BMC Complement Altern Med ; 19(1): 307, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31711473

RESUMO

BACKGROUND: Asphodelus tenuifolius Cav. (Asphodelaceae) has traditional reputability in treatment of diarrhea and constipation but no scientific study has been reported for its gastrointestinal effects. Present study was conducted to evaluate antidiarrheal and laxative activities of the plant. METHODS: Aqueous-ethanol crude extract of Asphodelus tenuifolius (At.Cr) was subjected to phytochemical screening and liquid-liquid fractionation. In vivo studies of charcoal meal intestinal transit test, antidiarrheal activity against castor oil induced diarrhea and laxative activity were performed in mice. In vitro experiments were conducted upon rabbit jejunum preparations using standard tissue bath techniques. RESULTS: Phytochemical screening indicated presence of alkaloids, anthraquinones, flavonoids, saponins, steroids, tannins and phenols in At.Cr. In charcoal meal intestinal transit test, At.Cr increased (p < 0.001) intestinal motility at 100 mg/kg dose, but decreased (p < 0.001) it at 500 mg/kg dose, when compared to the control group. At.Cr (300-700 mg/kg) provided protection from castor oil induced diarrhea in mice, which was significant (p < 0.001) at 500 and 700 mg/kg doses, as compared to the saline treated control group. At.Cr (50 and 100 mg/kg) enhanced total and wet feces counts in normal mice, as compared to saline treated control. In jejunum preparations, At.Cr inhibited spontaneous, K+ (80 mM) and K+ (25 mM) mediated contractions, similar to verapamil. Pre-incubation of jejunum preparations with At.Cr resulted in rightward nonparallel shift in Ca+ 2 concentration response curves, similar to verapamil. The spasmolytic activity was concentrated in ethylacetate fraction. Aqueous fraction exhibited spasmogenicity upon spontaneous contractions, which was blocked in presence of verapamil, but remained unaffected by other tested antagonists. CONCLUSION: The Asphodelus tenuifolius crude extract possesses gut modulatory activity, which may normalize gut functions in diarrhea and constipation. The spasmolytic activity of the extract was found to be mediated through Ca+ 2 channel blocking action. The spasmogenic activity, found partitioned in aqueous fraction, possibly involves Ca+ 2 influx through voltage gated Ca+ 2 channels. The study supports ethnic uses of the plant in diarrhea and constipation.


Assuntos
Antidiarreicos/administração & dosagem , Asparagales/química , Constipação Intestinal/tratamento farmacológico , Diarreia/tratamento farmacológico , Laxantes/administração & dosagem , Extratos Vegetais/administração & dosagem , Animais , Antidiarreicos/química , Antidiarreicos/isolamento & purificação , Constipação Intestinal/fisiopatologia , Diarreia/fisiopatologia , Feminino , Motilidade Gastrointestinal/efeitos dos fármacos , Íleo/efeitos dos fármacos , Íleo/fisiopatologia , Laxantes/química , Laxantes/isolamento & purificação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Coelhos
13.
Fitoterapia ; 139: 104367, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31629045

RESUMO

Ca2+-activated Cl- channels (CaCCs) wildly exist in many tissues which play an important role in ion transport and excitation conduction, especially fluid secretion and smooth muscle contraction in epithelial tissues. TMEM16A as a classic CaCC expresses in the intestine, and has become a potential target of intestinal physiological and pathological researches and therapeutic drug screening. In this study, we identified trans-δ-viniferin (TVN), a resveratrol dimmer, could inhibit TMEM16A activity in TMEM16A expressed FRT cells with IC50 of 19.7 µM, it also prevented Ca2+-activated Cl- current in HT-29 cells with IC50 of 4.65 µM and in colonic mucosa. In the mechanism studies, TVN showed no significant inhibition on CFTR and basal Na+/K+-ATPase in both intestinal epithelial cells and colonic tissues, except for inhibition of calcium concentration and Ca2+-activated K+ channel to some degree. In anti-diarrheal studies, TVN could effectively prevent diarrhea caused by rotavirus infection and reduce the pellet number in IBS-D mice. These physiological effects are at least partially attributed to the inhibitory effect of TVN on CaCC-mediated intestinal fluid secretion and the reduction of smooth muscle contraction force by inhibiting TMEM16A. Collectively, the present study identified a new pharmacological target of TVN which provided the theoretical basis for the application of TVN in the treatment of rotavirus-infected diarrhea and IBS-D.


Assuntos
Benzofuranos/farmacologia , Canais de Cloreto/antagonistas & inibidores , Diarreia/tratamento farmacológico , Células Epiteliais/efeitos dos fármacos , Resorcinóis/farmacologia , Estilbenos/farmacologia , Animais , Cálcio/análise , Diarreia/virologia , Motilidade Gastrointestinal/efeitos dos fármacos , Células HT29 , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Mucosa Intestinal/citologia , Camundongos , Camundongos Endogâmicos C57BL , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Ratos , Rotavirus
14.
J Vet Med Sci ; 81(12): 1810-1816, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31645506

RESUMO

Vincristine, one of the anti-cancer drugs used in veterinary practice, has adverse hematological and gastrointestinal effects in dogs. Juzen-taiho-to is a traditional Chinese medicine used for patients with anorexia in human medicine. However, the protective effects of Juzen-taiho-to against anti-cancer drug-induced toxicity in dogs have not been investigated. We therefore examined whether the administration of Juzen-taiho-to to dogs affects gastric motility, and vincristine-induced gastrointestinal and hematological toxicity. The study was composed of three trials. In the first trial, Juzen-taiho-to (450 mg/kg/day) was orally administered to five dogs. In the second and third trials, vincristine (0.75 mg/m2) was intravenously administered to each dog in the absence or presence of Juzen-taiho-to (450 mg/kg/day). During these trials, gastric motility and blood parameters were assessed. Juzen-taiho-to increased gastric motility and improved vincristine-induced gastrointestinal, but not hematological, adverse effects in dogs. This study suggested that Juzen-taiho-to may be applicable for gastrointestinal care in dogs receiving chemotherapy.


Assuntos
Antineoplásicos/toxicidade , Medicamentos de Ervas Chinesas/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacos , Vincristina/toxicidade , Animais , Contagem de Células Sanguíneas/veterinária , Cães , Feminino , Hematócrito/veterinária , Hemoglobinas/efeitos dos fármacos , Antro Pilórico/diagnóstico por imagem , Ultrassonografia/veterinária
15.
Mol Med Rep ; 20(6): 5050-5058, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31638214

RESUMO

Ghrelin is an orexigenic hormone that is produced by gastric cells. Ghrelin stimulates food intake and increases gastric movement. In rat model, injected ß­hydroxybutyric acid (ß­HB) leads to a decrease in body weight. It has been reported that patients with gastric erosions are slower to evacuate the stomach. The aim of the present study was to investigate the effects of ghrelin and ß­HB on motility and inflammation in rat gastric antral smooth muscle cells (GASMCs). GASMCs were extracted from rat gastric antrum. Cell viability was determined using the Cell Counting Kit­8 assay. A reactive oxygen species (ROS) assay kit was used to analyze the levels of ROS using flow cytometry. Protein levels were determined using western blotting, and the expression levels of mRNAs were evaluated using reverse transcription­quantitative PCR. ß­HB inhibited the expression of myosin regulatory light polypeptide 9 (MYL9), myosin light chain kinase (MLCK), transforming protein RhoA (RhoA), Rho­associated protein kinase­1 (ROCK­1) and growth hormone secretagogue receptor (GHS­R). By contrast, ghrelin increased the expression of MYL9, MLCK, RhoA, ROCK­1 and GHS­R in ß­HB­treated GASMCs. ß­HB increased the levels of tumor necrosis factor (TNF)­α, interleukin (IL)­6 and ROS, and decreased the levels of manganese (Mn) superoxide dismutase (SOD), copper/zinc (Cu/Zn)SOD and catalase. Ghrelin decreased the expression of TNF­α, IL­6, ROS and catalase, whereas ghrelin promoted the expression of MnSOD and Cu/ZnSOD in ß­HB­treated GASMCs. Short interfering RNA targeting GHS­R inhibited the expression of MYL9, MLCK, RhoA and ROCK­1, and increased the levels of TNF­α, IL­6 and ROS in ß­HB­treated or ghrelin­treated GASMCs. The present study provided preliminary evidence that ß­HB inhibits the motility of GASMCs and promotes inflammation in GASMCs, whereas ghrelin decreases these effects. GHS­R acted as a primary regulator of motility and inflammation in GASMCs treated with ß­HB and ghrelin.


Assuntos
Ácido 3-Hidroxibutírico/farmacologia , Movimento Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Grelina/farmacologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Receptores de Grelina/genética , Animais , Biomarcadores , Sobrevivência Celular/efeitos dos fármacos , Suscetibilidade a Doenças , Feminino , Motilidade Gastrointestinal/efeitos dos fármacos , Motilidade Gastrointestinal/genética , Humanos , Masculino , Oxirredução , Ratos , Espécies Reativas de Oxigênio/metabolismo , Receptores de Grelina/metabolismo
16.
Pak J Pharm Sci ; 32(3 Special): 1333-1342, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31551212

RESUMO

The MIC and MBC values of Shikuqin (SKQ) against 5 bacteria that readily cause diarrhea were measured by the broth micro dilution method. The castor oil-induced diarrhea method was used to evaluate the antidiarrheal activity. Intestinal transit and gastric emptying were also evaluated with normal and neostigmine-induced intestinal transit in rodents. In addition, the antidiarrheal activity of SKQ was assessed in vivo with isolated rabbit ileum. Xylene-induced ear edema was used to evaluate the anti-inflammatory activities in mice, while hot plate and writhing tests were performed to assess the analgesic effects. Senna decoction (0.3g/mL) was administered intragastrically to induce a rat model of diarrhea. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect AQP4 mRNA, and Western blot was performed to quantify the protein level of AQP4 in the colon. SKQ exhibits remarkable antidiarrheal, anti-inflammatory and analgesic effects in the gastrointestinal tract disorders, and can therefore be developed as a promising antidiarrheal agent.


Assuntos
Analgésicos/farmacologia , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Antidiarreicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Animais , Aquaporina 4/genética , Aquaporina 4/metabolismo , Óleo de Rícino/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Avaliação Pré-Clínica de Medicamentos , Edema/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Feminino , Motilidade Gastrointestinal/efeitos dos fármacos , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Pós , Coelhos , Ratos Sprague-Dawley
17.
Surgery ; 166(6): 1048-1054, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31543322

RESUMO

BACKGROUND: Intestinal inflammation is the predominant contributor to the genesis of postoperative ileus. Janus kinase 1 plays an important role during inflammation. Here, we investigated the role of Janus kinase 1 in postoperative ileus and whether inhibition of Janus kinase 1 could mitigate postoperative ileus. METHODS: A mouse model of postoperative ileus was induced by intestinal manipulation. Janus kinase 1 inhibitor GLPG0634 or placebo was administered orally before intestinal manipulation. At the indicated time points post operation, neutrophil infiltration was assessed by immunohistochemistry and enzyme-linked immunosorbent assay; proinflammatory gene expression was quantified by quantitative reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay; and Janus kinase 1 activation was detected by Western blot. Functional studies were conducted to evaluate intestinal motility. RESULTS: We found that intestinal manipulation led to marked activation of Janus kinase 1, with increased proinflammatory gene expression and upregulated myeloperoxidase level. Moreover, intestinal manipulation resulted in an impairment of intestinal transit in vivo and inhibition of smooth muscle contractility in vitro. Preoperative administration of GLPG0634 markedly lowered the expression of proinflammatory cytokines, the myeloperoxidase level in the muscularis layer after bowel manipulation, and significantly ameliorated smooth muscle contractile function and intestinal transit ability. CONCLUSION: Our data showed that Janus kinase 1 activation mediated intestinal manipulation-induced resident macrophage activation after intestinal manipulation, and subsequent complex inflammatory cascade and gut dysmotility. Janus kinase 1 inhibition appears to be a prospective and convenient approach for the prevention of postoperative ileus.


Assuntos
Íleus/prevenção & controle , Janus Quinase 1/antagonistas & inibidores , Jejuno/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Piridinas/administração & dosagem , Triazóis/administração & dosagem , Animais , Modelos Animais de Doenças , Motilidade Gastrointestinal/efeitos dos fármacos , Motilidade Gastrointestinal/imunologia , Humanos , Íleus/etiologia , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/cirurgia , Janus Quinase 1/metabolismo , Jejuno/efeitos dos fármacos , Jejuno/imunologia , Masculino , Camundongos , Contração Muscular/efeitos dos fármacos , Contração Muscular/imunologia , Músculo Liso/efeitos dos fármacos , Músculo Liso/imunologia , Peroxidase/metabolismo , Complicações Pós-Operatórias/etiologia , Cuidados Pré-Operatórios/métodos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Regulação para Cima/efeitos dos fármacos
18.
Vet J ; 251: 105345, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31492389

RESUMO

A constant rate infusion (CRI) of medetomidine is used to balance equine inhalation anesthesia, but its cardiovascular side effects are a concern. This experimental crossover study aimed to evaluate the effects of vatinoxan (a peripheral α2-adrenoceptor antagonist) on cardiorespiratory and gastrointestinal function in anesthetized healthy horses. Six horses received medetomidine hydrochloride 7µg/kg IV alone (MED) or with vatinoxan hydrochloride 140µg/kg IV (MED+V). Anesthesia was induced with midazolam and ketamine and maintained with isoflurane and medetomidine CRI for 60min. Heart rate, carotid and pulmonary arterial pressures, central venous pressure, cardiac output and arterial and mixed venous blood gases were measured. Selected cardiopulmonary parameters were calculated. Plasma drug concentrations were determined. Fecal output was measured over 24h. For statistical comparisons, repeated measures analysis of covariance and paired t-tests were applied. Heart rate decreased slightly from baseline in the MED group. Arterial blood pressures decreased with both treatments, but significantly more dobutamine was needed to maintain normotension with MED+V (P=0.018). Cardiac index (CI) and oxygen delivery index (DO2I) decreased significantly more with MED, with the largest difference observed at 20min: CI was 39±2 and 73±18 (P=0.009) and DO2I 7.4±1.2 and 15.3±4.8 (P=0.014)mL/min/kg with MED and MED+V, respectively. Fecal output or plasma concentrations of dexmedetomidine did not differ between the treatments. In conclusion, premedication with vatinoxan induced hypotension, thus its use in anesthetized horses warrants further studies. Even though heart rate and arterial blood pressures remained clinically acceptable with MED, cardiac performance and oxygen delivery were lower than with MED+V.


Assuntos
Motilidade Gastrointestinal/efeitos dos fármacos , Isoflurano/farmacologia , Medetomidina/farmacologia , Quinolizinas/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 2 , Anestesia por Inalação/veterinária , Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Fenômenos Fisiológicos Cardiovasculares/efeitos dos fármacos , Estudos Cross-Over , Feminino , Frequência Cardíaca/efeitos dos fármacos , Cavalos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Isoflurano/administração & dosagem , Masculino , Medetomidina/administração & dosagem , Quinolizinas/sangue , Quinolizinas/farmacocinética
19.
World J Gastroenterol ; 25(29): 3956-3971, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31413530

RESUMO

BACKGROUND: Irritable bowel syndrome (IBS) is a common chronic non-organic disease of the digestive system. Berberine (BBR) has been used to treat patients with IBS, but the underlying therapeutic mechanism is little understood. We believe that BBR achieves its therapeutic effect on IBS by preventing stress intestinal inflammation and visceral hypersensitivity and reducing bowel motility. AIM: To test the hypothesis that BBR achieves its therapeutic effect on IBS by preventing subclinical inflammation of the intestinal mucosa and reducing visceral hypersensitivity and intestinal motility. METHODS: IBS was induced in rats via water avoidance stress (WAS). qRT-PCR and histological analyses were used to evaluate the levels of cytokines and mucosal inflammation, respectively. Modified ELISA and qRT-PCR were used to evaluate the nuclear factor kappa-B (NF-κB) signal transduction pathway. Colorectal distention test, gastrointestinal transit measurement, Western blot, and qRT-PCR were used to analyze visceral sensitivity, intestinal motility, the expression of C-kit (marker of Cajal mesenchymal cells), and the expression of brain derived neurotrophic factor (BDNF) and its receptor TrkB. RESULTS: WAS led to mucosal inflammation, visceral hyperalgesia, and high intestinal motility. Oral administration of BBR inhibited the NF-κB signal transduction pathway, reduced the expression of pro-inflammatory cytokines [interleukin (IL)-1ß, IL-6, interferon-γ, and tumor necrosis factor-α], promoted the expression of anti-inflammatory cytokines (IL-10 and transforming growth factor-ß), and improved the terminal ileum tissue inflammation. BBR inhibited the expression of BDNF, TrkB, and C-kit in IBS rats, leading to the reduction of intestinal motility and visceral hypersensitivity. The therapeutic effect of BBR at a high dose (100 mg/kg) was superior to than that of the low-dose (25 mg/kg) group. CONCLUSION: BBR reduces intestinal mucosal inflammation by inhibiting the intestinal NF-κB signal pathway in the IBS rats. BBR reduces the expression of BDNF, its receptor TrkB, and C-kit. BBR also reduces intestinal motility and visceral sensitivity to achieve its therapeutic effect on IBS.


Assuntos
Berberina/farmacologia , Sistema Nervoso Entérico/efeitos dos fármacos , Hiperalgesia/tratamento farmacológico , Síndrome do Intestino Irritável/tratamento farmacológico , Estresse Psicológico/complicações , Animais , Berberina/uso terapêutico , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Sistema Nervoso Entérico/fisiopatologia , Motilidade Gastrointestinal/efeitos dos fármacos , Motilidade Gastrointestinal/imunologia , Humanos , Hiperalgesia/fisiopatologia , Hiperalgesia/psicologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/inervação , Síndrome do Intestino Irritável/imunologia , Síndrome do Intestino Irritável/psicologia , Masculino , Ratos , Estresse Psicológico/psicologia , Resultado do Tratamento
20.
Pharmacol Rep ; 71(5): 899-908, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31421543

RESUMO

BACKGROUND: Dietary interventions can improve gastrointestinal (GI) symptoms. We determined the effects of fatty acids (FAs) supplementation with medium- and long-chain saturated FAs on mouse GI motility and correlated them with the expression of genes for free FA receptors (FFAR)1-4, FA binding protein 4 (FABP4) and inflammation. METHODS: Forty-eight BalbC were assigned to: standard diet (STD), diet rich in medium-chain saturated FAs (COCO) and long-chain saturated FAs (HF) (7% by weight). Body weight (BW) and food intake (FI) were monitored for 8-weeks. GI motility was determined by fecal pellet output (FPO) and colon bead expulsion tests. FABP4 inhibitor, BMS309403 (1mg/kg, ip) was injected to half of each group 2 days/week. mRNA expression of FABP4, (FFAR)1-4, and pro-inflammatory cytokines were measured in colonic and splenic tissues using real-time PCR. RESULTS: COCO and HF decreased FI. COCO accelerated overall GI transit (p<0.05). COCO increased the mRNA expression of FFAR2 (p<0.001) and TNFα (p<0.01); HF increased the expression of FABP4 and FFAR4 (p<0.05), and FFAR2 (p<0.001) in the colon, and decreased FFAR1 and FFAR4 (p<0.001), TNFα (p<0.01) and IL-1ß (p<0.05) in splenic tissues. BMS309403 decreased the FI and delayed colonic transit in STD+BMS and COCO+BMS vs. STD (p<0.05). HF+BMS increased colonic expression of FFAR3 (p<0.01), TNFα (p<0.01), IL-6 (p<0.01), and reduced FFAR4 (p<0.05); COCO+BMS decreased TNFα (p<0.01). CONCLUSION: Diversification in the dietary lipid content affected GI motility in mice and the expression of FFARs and pro-inflammatory cytokines in vivo.


Assuntos
Colo/efeitos dos fármacos , Gorduras na Dieta/farmacologia , Ácidos Graxos/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Baço/efeitos dos fármacos , Animais , Colo/imunologia , Colo/metabolismo , Citocinas/genética , Proteínas de Ligação a Ácido Graxo/genética , Metabolismo dos Lipídeos/genética , Masculino , Camundongos Endogâmicos BALB C , Receptores Acoplados a Proteínas-G/genética , Baço/imunologia , Baço/metabolismo
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