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1.
World J Gastroenterol ; 28(34): 5007-5022, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36160643

RESUMO

BACKGROUND: Slow transit constipation (STC) is a common intestinal disease with increasing incidence. STC results from various factors, such as the enteric nervous system and metabolic changes. As a classical formula of traditional Chinese medicine, Ji-Chuan decoction (JCD) has been extensively and effectively used in STC treatment, yet its pharmacological mechanism remains unclear. AIM: To explore the integrated regulatory pattern of JCD against STC through hyphenated techniques from metabolism, network pharmacology and molecular methods. METHODS: STC model mice were generated by intragastric administration of compound diphenoxylate (10 mg/kg/d) for 14 d. The STC mice in the low dose of JCD (3.04 g/kg), middle dose of JCD (6.08 g/kg) and high dose of JCD (12.16 g/kg) groups were orally administered JCD solution once a day for 2 wk. The acetylcholine (ACH) level was examined by enzyme-linked immunosorbent assay. The pathological features of colon tissue were observed by hematoxylin and eosin staining. The differentially expressed metabolites and metabolic pathways were tested by nontargeted metabolomics. The main targets and core ingredients of JCD were identified by network pharmacology, and the expression of AKT was confirmed by immunohistochemistry. Finally, the pathways involved in JCD treatment were predicted using a combination of differentially expressed metabolites and targets, and intestinal glial cell apoptosis was demonstrated by immunofluorescence. RESULTS: JCD significantly promoted intestinal motility, increased the levels of the excitatory neurotransmitter ACH and reduced intestinal inflammation in STC mice. Untargeted metabolomics results showed that JCD significantly restored metabolic dysfunction and significantly affected taurine and hypotaurine metabolism. Network pharmacology and molecular experiments showed that JCD regulates AKT protein expression, and the core component is quercetin. Combined analysis demonstrated that apoptosis may be an important mechanism by which JCD relieves constipation. Further experiments showed that JCD reduced enteric glial cell (EGC) apoptosis. CONCLUSION: This work demonstrated that reducing EGC apoptosis may be the critical mechanism by which JCD treats STC. These findings call for further molecular research to facilitate the clinical application of JCD.


Assuntos
Acetilcolina , Difenoxilato , Animais , Apoptose , Constipação Intestinal , Trânsito Gastrointestinal , Camundongos , Neuroglia/metabolismo , Proteínas Proto-Oncogênicas c-akt , Quercetina , Taurina
2.
J Biosci ; 462021.
Artigo em Inglês | MEDLINE | ID: mdl-34544909

RESUMO

Slow transit constipation (STC) is a gastrointestinal disorder characterized by abnormal prolonged colonic transit time, which affects the life quality of many people. The decrease number of interstitial cells of Cajal (ICCs) is involved in the pathogenesis of STC. However, the molecular mechanism of loss of ICCs in STC remains unclear, making it difficult to develop new agents for the disease. In this study, we investigated the mechanism of decreasing ICCs in the pathogenesis of STC. We constructed the STC model rats by using atropine and diphenoxylate. A series of methods were used including immunofluorescence and immunochemistry staining, western blot, qRT-PCR, exosomes extraction and exosomes labeling. The results indicate that ICCs decreased in the STC rats accompanied with the macrophages activation. Further studies suggested that macrophages decreased the cell viability of ICCs by secretion exosomes containing miR-34c-5p. miR-34c5p targeted the 3Ꞌ -UTR of stem cell factor(SCF) mRNA and regulated the expression of SCF negatively. In conclusion, we demonstrated a novel regulatory mechanism of ICCs cell viability in STC. We found that exosome miR-34c-5p mediate macrophage-ICCs cross-talk. M1 macrophages derived exosomes miR-34c-5p decreased ICCs cell viability by directly targeting SCF.


Assuntos
Exossomos/metabolismo , Células Intersticiais de Cajal/fisiologia , Macrófagos/metabolismo , MicroRNAs/metabolismo , Fator de Células-Tronco/metabolismo , Analgésicos Opioides/farmacologia , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Atropina/farmacologia , Sobrevivência Celular/fisiologia , Constipação Intestinal , Difenoxilato/farmacologia , Motilidade Gastrointestinal , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , MicroRNAs/genética , Antagonistas Muscarínicos/farmacologia , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Células-Tronco/genética
3.
Drug Des Devel Ther ; 15: 1971-1980, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34007157

RESUMO

AIM: The naturally fermented yak yogurt of pastoralists in the Tibetan Plateau, China, because of its unique geographical environment and the unique lifestyle of Tibetan pastoralists, is very different from other kinds of sour milk, and the microorganisms it contains are special. Lactococcus lactis subsp. lactis HFY14 (LLSL-HFY14) is a new lactic acid bacterium isolated from naturally fermented yak yogurt. The purpose of this study was to study the inhibitory effect of the bacterium on constipation. METHODS: Constipation was induced in ICR mice with diphenoxylate, and the constipated mice were treated with LLSL-HFY14. The weight and feces of the mice were visually detected. Colonic tissues were observed on hematoxylin and eosin-stained sections. Serum indices were detected with kits. mRNA expression in the colon was determined by quantitative polymerase chain reaction assay. RESULTS: Constipation caused weight loss, the number of defecation granules, defecation weight, fecal water content decreased, and the first black stool excretion time increased. LLSL-HFY14 alleviated these symptoms, and the effects were similar to those of lactulose (drug). The pathological examination revealed that constipation caused pathological changes in the colon, and LLSL-HFY14 effectively alleviated the disease. LLSL-HFY14 increased serum levels of motilin, gastrin, endothelin, substance P, acetylcholinesterase, and vasoactive intestinal peptide (VIP) and decreased serum levels of somatostatin in constipated mice. In addition, LLSL-HFY14 upregulated VIP, cAMP, protein kinase A, and aquaporin 3 expression in colonic tissues of constipated mice in a dose-dependent manner. CONCLUSION: LLSL-HFY14 inhibited constipation, similar to lactulose, and has the potential to become a biological agent.


Assuntos
Constipação Intestinal/terapia , Lactococcus lactis/fisiologia , Probióticos/farmacologia , Iogurte/microbiologia , Animais , Aquaporina 3/metabolismo , Bovinos , Constipação Intestinal/microbiologia , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Difenoxilato/toxicidade , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos ICR , Transdução de Sinais , Somatostatina/sangue , Peptídeo Intestinal Vasoativo/metabolismo
4.
Food Res Int ; 143: 110273, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33992373

RESUMO

Slow transit constipation (STC) has become an epidemic medical problem. There are several kinds of drugs for constipation; however, each drug has its limitations. The gut microbiota has a close relationship with STC. Lactulose is an effective drug for constipation because it is a kind of bulking laxative and microbioecologic, and it relieves the syndromes of STC. We found that the Chinese Herb Solid Drink (CHSD), which contains medicine food homologous materials such as psyllium husk, sweetalmond, semen sesami nigrum, and hemp seed, has a similar effect on relieving constipation as lactulose, although it has different effects on the gut microbiota. We investigated the mechanisms of CHSD in rats with STC, induced by diphenoxylate, via constipation index and enzyme linked immunosorbent assay (ELISA) analyses using serum and 16S rDNA amplicon and gas chromatography-mass spectroscopy (GC-MS). CHSD enhanced the relative abundance of some types of gut microbiota, such as Blautia, Ruminococcus, Roseburia, Coprococcus, Lachnospira, and Phascolarctobacterium, while lactulose enhanced the relative abundance of Blautia, Phascolarctobacterium, Eubacterium, and Akkernansia in diphenoxylate-induced STC rats. Both CHSD and lactulose enhanced the level of short-chain fatty acids in the faeces of rats; however, the composition of those were different between the two drugs. From the perspective of the gut neuroendocrine system, both CHSD and lactulose could elevate neurotransmitters, such as motilin (MTL) and substance P (SP), which promote intestinal peristalsis and reduce the expression of vasoactive intestinal peptide, which inhibits intestinal peristalsis in the serum of STC rats. CHSD could elevate gastrin expression, which also promoted intestinal peristalsis in serum, while lactulose did not have this effect. Our findings suggest that CHSD may be an effective and safe therapeutic choice for STC.


Assuntos
Microbioma Gastrointestinal , Preparações Farmacêuticas , Animais , China , Constipação Intestinal , Difenoxilato , Lactulose , Ratos
5.
Food Funct ; 11(10): 9216-9225, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33030479

RESUMO

The prebiotics inulin (INU) and isomalto-oligosaccharide (IMO) influence intestinal health and immunity, but their effects on constipation are not clearly established. We evaluated the effects of INU and IMO in a rat model of diphenoxylate-induced constipation. Twenty-four male rats were divided into four groups: basal diet (Con), 40 mg kg-1 diphenoxylate (PCon), 20 g kg-1 INU and treated with 40 mg kg-1 diphenoxylate, and 20 g kg-1 IMO and treated with 40 mg kg-1 diphenoxylate. INU and IMO increased the number, weight, and water content of fecal pellets, and decreased the time to the first black stool in rats with constipation. Serum levels of the gastrointestinal motility-related hormones adrenocorticotropic hormone (ACTH), motilin (MTL), and Substance P (SP) were higher and corticosterone (CORT), vasoactive intestinal peptide (VIP), and calcitonin gene-related peptide (CGRP) were lower in rats treated with prebiotics than in untreated rats. Colon tissue levels of MTL and SP were increased, and VIP and CGRP were decreased by prebiotics. Furthermore, in rats with constipation, INU and IMO increased the colonic contents of short-chain fatty acids. The relative abundance of Bacteroidetes was lower in the prebiotics groups than in the Con and PCon groups. Lactobacillus was more abundant in the INU and IMO groups than in PCon rats. Lactobacillus reuteri and Lactobacillus intestinalis were more abundant in the IMO group than in the PCon group (P < 0.01), and L. intestinalis was more abundant in the INU group than in the PCon group (P < 0.01). In summary, INU and IMO improved constipation and altered the intestinal microbiota in a rat model of constipation.


Assuntos
Constipação Intestinal/tratamento farmacológico , Ácidos Graxos Voláteis/metabolismo , Hormônios Gastrointestinais/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Intestinos/microbiologia , Inulina/administração & dosagem , Oligossacarídeos/administração & dosagem , Prebióticos/análise , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/microbiologia , Constipação Intestinal/fisiopatologia , Difenoxilato/efeitos adversos , Fezes/microbiologia , Motilidade Gastrointestinal/efeitos dos fármacos , Humanos , Intestinos/fisiopatologia , Masculino , Ratos
6.
J Trauma Acute Care Surg ; 87(4): 915-921, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31574060

RESUMO

BACKGROUND: Acute noninfectious diarrhea is a common phenomenon in intensive care unit patients. Multiple treatments are suggested but the most effective management is unknown. A working group of the Eastern Association for the Surgery of Trauma, aimed to evaluate the effectiveness of loperamide, diphenoxylate/atropine, and elemental diet on acute noninfectious diarrhea in critically ill adults and to develop recommendations applicable to daily clinical practice. METHODS: The literature search identified 11 randomized controlled trials (RCT) appropriate for inclusion. The Grading of Recommendations Assessment, Development, and Evaluation methodology was applied to evaluate the effect of loperamide, diphenoxylate/atropine, and elemental diet on the resolution of noninfectious diarrhea in critically ill adults based on selected outcomes: improvement in clinical diarrhea, fecal frequency, time to the diarrhea resolution, and hospital length of stay. RESULTS: The level of evidence was assessed as very low. Analyses of 10 RCTs showed that loperamide facilitates resolution of diarrhea. Diphenoxylate/atropine was evaluated in three RCTs and was as effective as loperamide and more effective than placebo. No studies evaluating elemental diet as an intervention in patients with diarrhea were found. CONCLUSION: Loperamide and diphenoxylate/atropine are conditionally recommended to be used in critically ill patients with acute noninfectious diarrhea. LEVEL OF EVIDENCE: Systematic Review/Guidelines, level III.


Assuntos
Estado Terminal/terapia , Diarreia/etiologia , Diarreia/terapia , Dietoterapia/métodos , Difenoxilato/administração & dosagem , Loperamida/administração & dosagem , Adulto , Antidiarreicos/administração & dosagem , Diarreia/fisiopatologia , Motilidade Gastrointestinal/efeitos dos fármacos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
7.
Dig Dis Sci ; 64(12): 3385-3393, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31541370
8.
Int J Biol Macromol ; 133: 1090-1101, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31054300

RESUMO

The aim of this study is to probe new functions of a polysaccharide from Spirulina platensis (PSP) on constipation and intestinal microbiota in mice. Diphenoxylate-induced constipation in mice was treated with different doses of PSP, followed by examining the defecation patterns, levels of acetyl cholinesterase (AchE), nitric oxide (NO), and tissue section histopathology. The composition of intestinal microbiota was determined by genome sequencing analysis of the 16S rDNA. This study found that the average molecular weight of PSP was 29, 600 Da, and mainly monosaccharides of PSP were rhamnose (24.7%), glucose (16.15%) and galactose (13.32%). The beneficial effects of PSP treatment include defecation improvement, increase of AchE activity, reduction of NO concentration, renovation of the damaged intestinal villus and affection on the expression of some related genes in the constipated mice. In addition, PSP had significant effects on the gut microbiota, showing the enhancement in abundance of beneficial bacteria including Akkermansia, Lactobacillus, Butyricimonas, Candidatus Arthromitus and Prevotella, and the reduction in abundance of harmful bacteria such as Clostridium and Dorea. The present s uncovered a new function of PSP, indicating that PSP could be used in constipation therapies.


Assuntos
Constipação Intestinal/induzido quimicamente , Constipação Intestinal/tratamento farmacológico , Difenoxilato/efeitos adversos , Polissacarídeos Bacterianos/farmacologia , Spirulina/química , Animais , Vilosidades Coriônicas/efeitos dos fármacos , Vilosidades Coriônicas/metabolismo , Constipação Intestinal/metabolismo , Constipação Intestinal/fisiopatologia , Defecação/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Neurotransmissores/metabolismo , Polissacarídeos Bacterianos/uso terapêutico , Água/metabolismo
9.
Food Funct ; 10(3): 1513-1528, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30785176

RESUMO

Mulberry (Morus atropurpurea) has long been used to treat gastro-intestinal ailments; however, the functional basis of its therapeutic effects remains unclear. The aim of this study was to measure the effects of mulberry (administered by gavage) on diphenoxylate-induced constipation in mice and elucidate the mechanisms underlying these effects using constipation and physicochemical indexes, histological morphology and 16S rDNA amplicon analysis of fecal microbiota. Sixty Kunming mice were randomly divided into the following six groups (n = 10 per group): normal control, constipation model, positive control, and low-, mid- and high-dose mulberry groups. After 14 days of treatment, constipation was induced over 5 days and measurements were conducted. The results show that mulberry treatment prevented constipation by increasing the fecal water content, shortening the first red fecal defecation time, promoting gastric evacuation, and increasing the gastric-intestinal transit rate (P < 0.05). Compared with the constipation model group, the mulberry-treated groups showed decreased aquaporin gene expression (Aqp3, Aqp4, Aqp8 and Aqp9), decreased serum levels of inhibitory neurotransmitters (nitric oxide and vasoactive intestinal peptide) (P < 0.05), and increased serum levels of excitability neurotransmitters (acetyl choline, substance P, and motilin). The histological morphology of the colon showed that mulberry treatment increased the number of mucus cells (P < 0.05). Mulberry treatment also increased the concentrations of acetic, propionic, butyric, valeric and isovaleric acids (P < 0.05), increased the abundance of Lactobacillus and Bifidobacterium in feces, and decreased the abundance of Helicobacter and Prevotellaceae in feces. Our findings indicate that mulberry consumption effectively prevents constipation in mice and is a promising therapeutic candidate for constipation.


Assuntos
Constipação Intestinal/induzido quimicamente , Difenoxilato/toxicidade , Frutas/química , Microbioma Gastrointestinal/efeitos dos fármacos , Morus/química , Animais , Constipação Intestinal/dietoterapia , Camundongos
10.
Zhonghua Liu Xing Bing Xue Za Zhi ; 39(9): 1222-1227, 2018 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-30293314

RESUMO

Objective: To investigate the prevalence of diphenoxylate abuse and related factors of forced drug abstainer in Gansu province. Methods: By using a self-designed questionnaire, an epidemiologic investigation was carried out among 2 108 forced drug abstainer selected from the compulsory isolation detoxification center of Gansu province. A case-control study was conducted to analyze the factors related with diphenoxylate abuse. Results: The diphenoxylate abuse rate among forced drug abstainer in Gansu was 19.8% (406/2 046), ranking first in medical drug abuse. Multiple logistic regression analysis showed that factors as relieving withdrawal symptoms (OR=2.08, 95%CI: 1.01- 4.32), ways to obtain diphenoxylate (other ways: OR=1.00; regular clinic: OR=27.67, 95%CI: 2.64-289.82; friend: OR=0.01, 95%CI: 0.01-0.03), degree of euphoria (high: OR=1.00; medium: OR =3.36, 95%CI: 1.18-9.55; low: OR=26.16, 95%CI: 10.30-66.42), years of drug abuse (<5 years: OR=1.00; 10-15 years: OR=2.48, 95%CI: 1.02-6.04), abuse at home or in friend's house (OR=3.04, 95%CI: 1.08-8.68), abuse in car (OR=0.05, 95%CI: 0.00-0.68) and detoxification for the first time (OR=0.61, 95%CI: 0.43-0.86) were the possible influencing factors for diphenoxylate abuse. Conclusions: The prevalence of diphenoxylate abuse in forced drug abstainer in Gansu was relatively high. Reasons of abusing, the way to obtain diphenoxylate, whether using drug together with friends, degree of euphoria, years of abuse, abuse place and times for detoxification were related factors influencing the abuse of diphenoxylate.


Assuntos
Analgésicos Opioides/efeitos adversos , Difenoxilato/efeitos adversos , Síndrome de Abstinência a Substâncias , Transtornos Relacionados ao Uso de Substâncias , Analgésicos Opioides/provisão & distribuição , Estudos de Casos e Controles , China , Difenoxilato/provisão & distribuição , Humanos , Transtornos Relacionados ao Uso de Substâncias/etnologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Inquéritos e Questionários
11.
J Agric Food Chem ; 66(16): 4106-4117, 2018 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-29627986

RESUMO

This study was to probe the effects of bacterial cellulose (BC) on diphenoxylate-induced constipation in rats. Administration with BC at 500 mg/kg of body weight in diphenoxylate-induced constipation rats distinctly improved the carmine propulsion rate (83.5 ± 5.2%), shortened the defecating time of the first red feces (249.0 ± 23.3 min), and increased the weight of carmine red feces within 5 h (2.7 ± 1.3 g). The levels of aquaporins (AQP-2, AQP-3, and AQP-4) and inhibitory neurotransmitters (nitric oxide, nitric oxide synthetase, vasoactive intestinal peptide, and arginine vasopressin) in the BC-treated groups reduced by 31.9-40.0% ( p < 0.01) and 21.1-67.7% ( p < 0.01) compared to those in the constipation group, respectively. However, the secretion of excitability neurotransmitters (substance P and motilin) in the BC-treated groups was increased by 20.0-39.9% ( p < 0.01). The activities of ATPases in the colon of constipation rats were significantly weakened by BC administration ( p < 0.01). Histological morphology of the colon showed that BC supplementation could effectively increase the length of villus cells and the thickness of colonic mucosa and muscle ( p < 0.01). Moreover, BC supplementation could protect colonic smooth muscle cells against apoptosis. All of the findings suggest that BC supplementation effectively relieves constipation in rats and BC would be used as a great promising dietary fiber for alleviating constipation.


Assuntos
Acetobacteraceae/metabolismo , Celulose/administração & dosagem , Constipação Intestinal/tratamento farmacológico , Difenoxilato/efeitos adversos , Acetobacteraceae/química , Animais , Aquaporinas/metabolismo , Celulose/metabolismo , Constipação Intestinal/etiologia , Constipação Intestinal/metabolismo , Constipação Intestinal/fisiopatologia , Defecação/efeitos dos fármacos , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Masculino , Motilina/metabolismo , Ratos , Ratos Sprague-Dawley , Substância P/metabolismo
13.
Prog Transplant ; 27(1): 69-72, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27881814

RESUMO

Norovirus is a common self-limiting gastrointestinal infection, but in transplant recipients, symptoms can last for months and result in serious health complications. As there is currently no established treatment for chronic norovirus infection in transplant patients, management has been directed at symptom control, trial of various antivirals, and ultimately reductions in immunosuppression. We present 3 cases of chronic norovirus infection in cardiac transplant patients to illustrate various approaches to diagnosis, the prolonged nature of disease symptoms, and treatment options. When managing a transplant recipient with chronic diarrhea, considering a broad differential as well as maintaining a high suspicion for infectious etiologies is key. A stepwise approach to management includes termination of diarrhea-causing medications, trials of nitazoxanide and immunoglobulin, and reductions in immunosuppressive therapies. Although brief discontinuation of immunosuppression is often required to achieve symptom, graft rejection is often a complication.


Assuntos
Infecções por Caliciviridae/diagnóstico , Transplante de Coração , Transplantados , Adulto , Antidiarreicos/administração & dosagem , Atropina/administração & dosagem , Infecções por Caliciviridae/tratamento farmacológico , Doença Crônica , Difenoxilato/administração & dosagem , Combinação de Medicamentos , Feminino , Fármacos Gastrointestinais/administração & dosagem , Humanos , Imunossupressores/administração & dosagem , Loperamida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase
14.
Hippocampus ; 26(3): 289-300, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26314691

RESUMO

This study investigated behavioral, anatomical and electrophysiological effects produced by electrical stimulation of posterior hypothalamic (PH) or median raphe (MR) nuclei, independently and during combined stimulation of both PH and MR. These three stimulation conditions were applied during spontaneous behavior in an open field and during PH stimulation-induced wheel running, while simultaneously recording hippocampal (HPC) field activity. An additional objective was to determine the effects of MR stimulation on Type 1 movement related theta and Type 2 sensory processing related theta. To achieve the latter, when behavioral studies were completed we studied the same rats under urethane anesthesia and then during urethane anesthesia with the addition of atropine sulfate (ATSO4). Here we demonstrated that electrical stimulation of a localized region of the MR nucleus resulted in a profound inhibition of both spontaneously occurring theta related motor behaviors and the theta related motor behaviors induced by electrical stimulation of the PH nucleus. Furthermore, this motor inhibition occurred concurrently with strong suppression of hippocampal theta field oscillations in the freely moving rat, a condition where the theta recorded is Type 2 sensory processing theta occurring coincidently with Type 1 movement related theta (Bland, 1986). Our results indicate that motor inhibition resulted from stimulation of neurons located in the mid central region of the MR, while stimulation in adjacent regions produced variable responses, including movements and theta activity. The present study provided evidence that the pharmacological basis of the suppression of Type 2 sensory processing HPC theta was cholinergic. However, MR inhibition of PH-induced wheel running was not affected by cholinergic blockade, which blocks Type 2 theta, indicating that MR stimulation-induced motor inhibition also requires the suppression of Type 1 theta.


Assuntos
Núcleo Dorsal da Rafe/fisiologia , Hipocampo/fisiologia , Atividade Motora/fisiologia , Corrida/fisiologia , Ritmo Teta/fisiologia , Analgésicos Opioides/farmacologia , Animais , Atropina/farmacologia , Difenoxilato/farmacologia , Núcleo Dorsal da Rafe/efeitos dos fármacos , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Estimulação Elétrica , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Hipotálamo Posterior/fisiologia , Masculino , Atividade Motora/efeitos dos fármacos , Antagonistas Muscarínicos/farmacologia , Vias Neurais/fisiologia , Ratos , Ratos Long-Evans , Ritmo Teta/efeitos dos fármacos , Uretana/farmacologia
15.
Schmerz ; 27(2): 182-9, 2013 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-23475156

RESUMO

Diarrhea is a distressing symptom which limits the quality of life in patients receiving palliative care and is associated with high morbidity and mortality. In patients with AIDS, it is a more common problem than for other entities (e.g., cancer). Loperamide is considered the first choice medication for the symptomatic treatment of diarrhea. This literature review examines the efficacy of loperamide in the symptomatic treatment of diarrhea in palliative care. Two databases (Medline and Embase) were searched through June 2012. A total of 286 studies were identified, but only 7 met the inclusion criteria (1 cohort and 6 experimental studies) in which loperamide (alone or in combination) was tested. There is a lack of significant studies which investigate the efficacy of loperamide in the symptomatic treatment of diarrhea. Two trials indicated superiority of loperamide over placebo. In comparison with octreotide, the results were contradictory. The combination of acetorphan with loperamide was more effective than acetorphan alone, but the combination of loperamide with diphenoxylate was inferior to octreotide. The identified studies revealed methodical problems. A definite recommendation for administration of loperamide can, therefore, not be derived from this work.The English full-text version of this article is available at SpringerLink (under "Supplemental").


Assuntos
Antidiarreicos/uso terapêutico , Diarreia/tratamento farmacológico , Loperamida/uso terapêutico , Cuidados Paliativos , Síndrome de Imunodeficiência Adquirida/complicações , Antidiarreicos/efeitos adversos , Ensaios Clínicos Controlados como Assunto , Diarreia/etiologia , Difenoxilato/efeitos adversos , Difenoxilato/uso terapêutico , Quimioterapia Combinada , Humanos , Loperamida/efeitos adversos , Octreotida/efeitos adversos , Octreotida/uso terapêutico , Tiorfano/efeitos adversos , Tiorfano/análogos & derivados , Tiorfano/uso terapêutico
16.
Bioorg Med Chem Lett ; 22(23): 7106-9, 2012 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-23084278

RESUMO

Diphenoxylate, a well-known opioid agonist and anti-diarrhoeal agent, was recently found to block Kv1.3 potassium channels, which have been proposed as potential therapeutic targets for a range of autoimmune diseases. The molecular basis for this Kv1.3 blockade was assessed by the selective removal of functional groups from the structure of diphenoxylate as well as a number of other structural variations. Removal of the nitrile functional group and replacement of the C-4 piperidinyl substituents resulted in several compounds with submicromolar IC(50) values.


Assuntos
Difenoxilato/química , Canal de Potássio Kv1.3/química , Bloqueadores dos Canais de Potássio/química , Difenoxilato/síntese química , Difenoxilato/metabolismo , Humanos , Cinética , Canal de Potássio Kv1.3/metabolismo , Bloqueadores dos Canais de Potássio/síntese química , Bloqueadores dos Canais de Potássio/metabolismo , Ligação Proteica , Relação Estrutura-Atividade
17.
J Med Food ; 15(10): 930-5, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23039112

RESUMO

Banana oligosaccharides (BOS) were extracted with water, and then separated and purified using column chromatography. Gel penetration chromatography was used to determine the molecular weights. Thin layer chromatogram and capillary electrophoresis were employed to analyze the monosaccharide composition. The indican bond and structure of the BOS molecule were determined using Fourier transform infrared spectroscopy and nuclear magnetic resonance. Results showed that BOS were probably composed of eight ß-D-pyran glucose units linked with 1→6 indican bonds. The laxative effects of BOS were investigated in mice using the method described in "Handbook of Technical Standards for Testing and Assessment of Health Food in China." The length of the small intestine over which a carbon suspension solution advanced in mice treated with low-, middle-, and high-dose BOS was significantly greater than that in the model group, suggesting that BOS are effective in accelerating the movement of the small intestine.


Assuntos
Laxantes/farmacologia , Musa/química , Oligossacarídeos/química , Oligossacarídeos/farmacologia , Animais , China , Cromatografia em Gel , Cromatografia em Camada Delgada , Difenoxilato/farmacologia , Eletroforese Capilar , Intestino Delgado/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Camundongos , Peso Molecular , Oligossacarídeos/isolamento & purificação , Espectroscopia de Infravermelho com Transformada de Fourier
18.
J Pediatr Gastroenterol Nutr ; 53(4): 447-52, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21505362

RESUMO

OBJECTIVES: Constipation can adversely affect children's health, with disorders of host immunity and enhanced oxidative stress. As nondigestible carbohydrates, prebiotics can affect the host with constipation; however, whether the prebiotics have effects on the content of intestinal secretory immunoglobulin A (sIgA) and the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in constipation has not been fully clarified. METHODS: In the present study, constipation was induced in female Sprague-Dawley rats by diphenoxylate, and the prebiotics dissolved in milk were used as an intervention. The indicators of intestinal peristalsis, including the time of passing black stool initially, the grains of black stool in 24 hours, and the advance rate of ponceau, were measured. The content of intestinal sIgA was detected by enzyme-linked immunosorbent assay. The contents of SOD and MDA in serum and intestinal tissue were analyzed by their detection kits. RESULTS: The changes in intestinal peristalsis show obvious constipation. The content of intestinal sIgA decreases, the content of SOD decreases, but the content of MDA increases in constipated rats. Prebiotics can attenuate the constipation-caused abnormal indicators significantly. CONCLUSIONS: Prebiotics can attenuate decreased intestinal immunity and enhanced oxidative stress, in addition to reduced intestinal peristalsis and of the constipated rats.


Assuntos
Constipação Intestinal/induzido quimicamente , Constipação Intestinal/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Prebióticos , Animais , Difenoxilato/metabolismo , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Imunoglobulina A Secretora/análise , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Malondialdeído/sangue , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/sangue
19.
Clin Infect Dis ; 52(9): 1130-2, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21467017
20.
Zhong Yao Cai ; 34(10): 1565-9, 2011 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-22372147

RESUMO

OBJECTIVE: To research the effects of Na-FA on gastrointestinal movement and gastriculcer in mice. METHODS: Using charcoal powder as an indicator, the effects of FA-Na on bowel movement of mice was evaluated by determining the propulsive percent-age of charcoal powder in normal mice, inhibition of small intestinal propulsion model induced by Compound Diphenoxylate and spleen asthenia and diarrhea model caused by Rheum officinale Baill; The acute gastric ulcer model was induced by intragastric alcohol given orally, the protective effect of FA-Na given ahead on gastric injury was evaluated, the ulcer index and the inhibition ratio of ulcer was calculated. RESULTS: FA-Na (intragastric administration) had inhibit effect on normal mice and diarrhea model caused by Rheum officinale, significantly synergetic effect on gastrointestinal asynersis induced by Compound Diphenoxylate, and protective effect on mice gastric mucosal injury cause by dehydrated alcohol. Compared with the positive control drug Ranitidine, the ulcer index and ulcer inhibition ratio large doses of FA-Na had no significant difference. CONCLUSION: The acute toxicity of FA-Na is very low, it has the effects of antidiarrheal and anti-gastric ulcer.


Assuntos
Antiulcerosos/farmacologia , Benzopiranos/farmacologia , Quelantes/farmacologia , Gastroenteropatias/tratamento farmacológico , Motilidade Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/efeitos dos fármacos , Administração Oral , Animais , Antiulcerosos/uso terapêutico , Antidiarreicos/farmacologia , Antidiarreicos/uso terapêutico , Benzopiranos/uso terapêutico , Peso Corporal , Carbono/química , Quelantes/uso terapêutico , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Difenoxilato , Modelos Animais de Doenças , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/lesões , Gastroenteropatias/induzido quimicamente , Substâncias Húmicas , Masculino , Camundongos , Ranitidina/farmacologia , Ranitidina/uso terapêutico , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/prevenção & controle
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