Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.370
Filtrar
1.
Front Biosci (Landmark Ed) ; 29(2): 47, 2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38420828

RESUMO

BACKGROUND: The leaves of Origanum majorana (O. majorana) are traditionally renowned for treating diarrhea and gut spasms. This study was therefore planned to evaluate its methanolic extract. METHODS: Gas chromatography-mass spectrometry (GC-MS) was used to identify the phytochemicals, and Swiss albino mice were used for an in vivo antidiarrheal assay. Isolated rat ileum was used as an ex vivo assay model to study the possible antispasmodic effect and its mechanism(s). RESULTS: The GC-MS analysis of O. majorana detected the presence of 21 compounds, of which alpha-terpineol was a major constituent. In the antidiarrheal experiment, O. majorana showed a substantial inhibitory effect on diarrheal episodes in mice at an oral dosage of 200 mg/kg, resulting in 40% protection. Furthermore, an oral dosage of 400 mg/kg provided even greater protection, with 80% effectiveness. Similarly, loperamide showed 100% protection at oral doses of 10 mg/kg. O. majorana caused complete inhibition of carbachol (CCh, 1 µM) and high K+ (80 mM)-evoked spasms in isolated ileal tissues by expressing significantly higher potency (p < 0.05) against high K+ compared to CCh, similar to verapamil, a Ca++ antagonist. The verapamil-like predominant Ca++ ion inhibitory action of O. majorana was further confirmed in the ileal tissues that were made Ca++-free by incubating the tissues in a physiological salt solution having ethylenediaminetetraacetic acid (EDTA) as a chelating agent. The preincubation of O. majorana at increasing concentrations (0.3 and 1 mg/mL) shifted towards the right of the CaCl2-mediated concentration-response curves (CRCs) with suppression of the maximum contraction. Similarly, verapamil also caused non-specific suppression of Ca++ CRCs towards the right, as expected. CONCLUSIONS: Thus, this study conducted an analysis to determine the chemical constituents of the leaf extract of O. majorana and provided a detailed mechanistic basis for the medicinal use of O. majorana in hyperactive gut motility disorders.


Assuntos
Antidiarreicos , Origanum , Ratos , Camundongos , Animais , Antidiarreicos/farmacologia , Antidiarreicos/uso terapêutico , Antidiarreicos/química , Jejuno , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Óleo de Rícino/farmacologia , Óleo de Rícino/uso terapêutico , Diarreia/tratamento farmacológico , Verapamil/farmacologia , Verapamil/uso terapêutico , Canais de Cálcio , Espasmo/tratamento farmacológico
2.
J Complement Integr Med ; 21(1): 26-37, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38180845

RESUMO

OBJECTIVES: Nigeria ranks second in the global prevalence of diarrhoea with most cases concentrated in the Northern-region of the country. This research explored the antidiarrhoeal efficacy of the hydroethanolic extract of Piliostigma thonningii leaves (HEPTL), locally used to manage diarrhoeal conditions in Kebbi State, Nigeria. METHODS: P. thonningii leaves were screened for their secondary metabolites and mineral constituents. Using 3 standard-diarrhoea models, female Wistar rats completely-randomised into six-groups of six animals each were utilised for probing the antidiarrhoeal activity of HEPTL. Animals in groups I and II served as the negative and positive controls, whereas the rats in groups III, IV and V respectively received 50, 100, and 200 mg/kg body weight-(bw) of HEPTL. RESULTS: Six secondary metabolites and eight minerals were found in the extract, with flavonoids and calcium being the most abundant while steroids and zinc were the least prevalent, respectively. High performance liquid chromatographic analysis revealed the presence of 19 bioactive substances. Furthermore, there was a significant (p<0.05) and dose-related reduction in diarrhoea onset, water content, and wet faeces count. Similarly, the amount of intestinal fluid and average distance traversed by the charcoal-meal were decreased dose-dependently by the HEPTL with a commensurate rise in the suppression of intestinal fluid accrual and peristalsis. Acetylcholinesterase, Na+/K+-ATPase, reduced glutathione, intestinal-alkaline phosphatase and protein levels increased significantly (p<0.05) whereas superoxide-dismutase, catalase, intestinal-nitric oxide and malondialdehyde levels all fell significantly (p<0.05). However, the level of intestinal glucose was not significantly altered. CONCLUSIONS: Overall, the HEPTL exhibited a profound effect in the alleviation of the severity of diarrhoea, notably at 200 mg/kg bw.


Assuntos
Antidiarreicos , Fabaceae , Ratos , Feminino , Animais , Ratos Wistar , Antidiarreicos/farmacologia , Antidiarreicos/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/análise , Fitoterapia , Acetilcolinesterase , Óleo de Rícino/análise , Óleo de Rícino/uso terapêutico , Diarreia/tratamento farmacológico , Fabaceae/química , Folhas de Planta/química
3.
Front Biosci (Landmark Ed) ; 29(1): 43, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38287835

RESUMO

BACKGROUND: Medicinal herbs are frequently used for the management of gastrointestinal disorders because they contain various compounds that can potentially amplify the intended therapeutic effects. Cuminaldehyde is a plant-based constituent found in oils derived from botanicals such as cumin, eucalyptus, myrrh, and cassia and is responsible for its health benefits. Despite the utilization of cuminaldehyde for several medicinal properties, there is currently insufficient scientific evidence to support its effectiveness in treating diarrhea. Hence, the present investigation was carried out to evaluate the antidiarrheal and antispasmodic efficacy of cuminaldehyde, with detailed pharmacodynamics explored. METHODS: An in vivo antidiarrheal test was conducted in mice following the castor oil-induced diarrhea model, while an isolated small intestine obtained from rats was used to evaluate the detailed mechanism(s) of antispasmodic effects. RESULTS: Cuminaldehyde, at 10 and 20 mg/kg, exhibited 60 and 80% protection in mice from episodic diarrhea compared to the saline control group, whereas this inhibitory effect was significantly reversed in the pretreated mice with glibenclamide, similar to cromakalim, an ATP-dependent K+ channel opener. In the ex vivo experiments conducted in isolated rat tissues, cuminaldehyde reversed the glibenclamide-sensitive low K+ (25 mM)-mediated contractions at significantly higher potency compared to its inhibitory effect against high K+ (80 mM), thus showing predominant involvement of ATP-dependent K+ activation followed by Ca++ channel inhibition. Cromakalim, a standard drug, selectively suppressed the glibenclamide-sensitive low K+-induced contractions, whereas no relaxation was observed against high K+, as expected. Verapamil, a Ca++ channel inhibitor, effectively suppressed both low and high K+-induced contractions with similar potency, as anticipated. At higher concentrations, the inhibitory effect of cuminaldehyde against Ca++ channels was further confirmed when the preincubated ileum tissues with cuminaldehyde (3 and 10 mM) in Ca++ free medium shifted CaCl2-mediated concentration-response curves (CRCs) towards the right with suppression of the maximum peaks, similar to verapamil, a standard Ca++ ion inhibitor. CONCLUSIONS: Present findings support the antidiarrheal and antispasmodic potential of cuminaldehyde, possibly by the predominant activation of ATP-dependent K+ channels followed by voltage-gated Ca++ inhibition. However, further in-depth assays are recommended to know the precise mechanism and to elucidate additional unexplored mechanism(s) if involved.


Assuntos
Antidiarreicos , Benzaldeídos , Cimenos , Parassimpatolíticos , Ratos , Camundongos , Animais , Antidiarreicos/efeitos adversos , Parassimpatolíticos/efeitos adversos , Cromakalim/efeitos adversos , Glibureto/efeitos adversos , Extratos Vegetais/farmacologia , Jejuno , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Verapamil/efeitos adversos , Trifosfato de Adenosina
4.
Transl Res ; 263: 45-52, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37678755

RESUMO

Cyclic nucleotide elevation in intestinal epithelial cells is the key pathology causing intestinal fluid loss in secretory diarrheas such as cholera. Current secretory diarrhea treatment is primarily supportive, and oral rehydration solution is the mainstay of cholera treatment. There is an unmet need for safe, simple and effective diarrhea treatments. By promoting cAMP hydrolysis, extracellular calcium-sensing receptor (CaSR) is a regulator of intestinal fluid transport. We studied the antidiarrheal mechanisms of FDA-approved CaSR activator cinacalcet and tested its efficacy in clinically relevant human cell, mouse and intestinal organoid models of secretory diarrhea. By using selective inhibitors, we found that cAMP agonists-induced secretory short-circuit currents (Isc) in human intestinal T84 cells are mediated by collective actions of apical membrane cystic fibrosis transmembrane conductance regulator (CFTR) and Clc-2 Cl- channels, and basolateral membrane K+ channels. 30 µM cinacalcet pretreatment inhibited all 3 components of forskolin and cholera toxin-induced secretory Isc by ∼75%. In mouse jejunal mucosa, cinacalcet inhibited forskolin-induced secretory Isc by ∼60% in wild type mice, with no antisecretory effect in intestinal epithelia-specific Casr knockout mice (Casr-flox; Vil1-cre). In suckling mouse model of cholera induced by oral cholera toxin, single dose (30 mg/kg) oral cinacalcet treatment reduced intestinal fluid accumulation by ∼55% at 20 hours. Lastly, cinacalcet inhibited forskolin-induced secretory Isc by ∼75% in human colonic and ileal organoids. Our findings suggest that CaSR activator cinacalcet has antidiarrheal efficacy in distinct human cell, organoid and mouse models of secretory diarrhea. Considering its excellent clinical safety profile, cinacalcet can be repurposed as a treatment for cyclic nucleotide-mediated secretory diarrheas including cholera.


Assuntos
Antidiarreicos , Cólera , Camundongos , Humanos , Animais , Antidiarreicos/metabolismo , Antidiarreicos/farmacologia , Antidiarreicos/uso terapêutico , Cólera/tratamento farmacológico , Cólera/metabolismo , Cólera/patologia , Toxina da Cólera/metabolismo , Toxina da Cólera/farmacologia , Toxina da Cólera/uso terapêutico , Cinacalcete/farmacologia , Cinacalcete/uso terapêutico , Cinacalcete/metabolismo , Receptores de Detecção de Cálcio/metabolismo , Receptores de Detecção de Cálcio/uso terapêutico , Nucleotídeos Cíclicos/metabolismo , Nucleotídeos Cíclicos/farmacologia , Nucleotídeos Cíclicos/uso terapêutico , Colforsina/metabolismo , Colforsina/farmacologia , Colforsina/uso terapêutico , Diarreia/tratamento farmacológico , Diarreia/metabolismo , Mucosa Intestinal/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/uso terapêutico , Camundongos Knockout
5.
Int J Radiat Oncol Biol Phys ; 118(3): 616-625, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37742773

RESUMO

PURPOSE: There is currently no gold standard for the management of acute radiation enteritis. We compared the efficacy and safety of Racecadotril, an anti-hypersecretory drug, versus Loperamide, an anti-motility agent, in acute radiation enteritis. METHODS AND MATERIALS: We conducted a randomized, double-masked, non-inferiority trial at a single research institute. Patients receiving curative radiation for pelvic malignancies, who developed grade 2 or 3 diarrhea (as per Common Terminology Criteria for Adverse Events, v 4.0) were included in the study. Patients in the intervention arm received Racecadotril and placebo. Patients in the control arm received Loperamide and placebo. The primary outcome was the resolution of diarrhea, 48 hours after the start of treatment. RESULTS: 162 patients were randomized between 2019 and 2022. On intention-to-treat analysis, 68/81 patients, 84%, (95% CI, 74.1%-91.2%) in the Racecadotril arm and 70/81, 86.4%, (95% CI, 77.0%-93.0%) in the Loperamide arm improved from grade 2 or 3 diarrhea to grade 1 or 0, (P= .66, χ2 test). The difference in proportion was 2.4% (95% CI: -8.5% to 13.4%). Since the upper boundary of the 95% CI crossed our non-inferiority margin of 10% (13.4%) we could not prove the non-inferiority of Racecadotril over Loperamide. Rebound constipation was more in the Loperamide arm compared to Racecadotril (17.3% vs 6.2%; P = .028) CONCLUSIONS: The non-inferiority of Racecadotril to Loperamide in acute radiation enteritis could not be demonstrated. However, Racecadotril can be the preferred drug of choice in acute radiation enteritis because Racecadotril does not affect bowel motility, achieved a high clinical success rate similar to that of Loperamide, and was associated with lesser side effects.


Assuntos
Síndrome Aguda da Radiação , Enterite , Tiorfano , Humanos , Doença Aguda , Síndrome Aguda da Radiação/tratamento farmacológico , Antidiarreicos/efeitos adversos , Diarreia/tratamento farmacológico , Diarreia/etiologia , Método Duplo-Cego , Enterite/etiologia , Enterite/induzido quimicamente , Loperamida/efeitos adversos , Tiorfano/análogos & derivados
6.
Eur J Pharmacol ; 965: 176289, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38158111

RESUMO

Piperine is a natural alkaloid that possesses a variety of therapeutic properties, including anti-inflammatory, antioxidant, antibacterial, and anticarcinogenic activities. The present study aims to assess the medicinal benefits of piperine as an anti-diarrheal agent in a chick model by utilizing in vivo and in silico techniques. For this, castor oil was administered orally to 2-day-old chicks to cause diarrhea. Bismuth subsalicylate (10 mg/kg), loperamide (3 mg/kg), and nifedipine (2.5 mg/kg) were used as positive controls, while the vehicle was utilized as a negative control. Two different doses (25 and 50 mg/kg b.w.) of the test sample (piperine) were administered orally, and the highest dose was tested with standards to investigate the synergistic activity of the test sample. In our findings, piperine prolonged the latent period while reducing the number of diarrheal feces in the experimental chicks during the monitoring period (4 h). At higher doses, piperine appears to reduce diarrheal secretion while increasing latency in chicks. Throughout the combined pharmacotherapy, piperine outperformed bismuth subsalicylate and nifedipine in terms of anti-diarrheal effects with loperamide. In molecular docking, piperine exhibited higher binding affinities towards different inflammatory enzymes such as cyclooxygenase 1 (-7.9 kcal/mol), cyclooxygenase 2 (-8.4 kcal/mol), nitric oxide synthases (-8.9 kcal/mol), and L-type calcium channel (-8.8 kcal/mol), indicating better interaction of PP with these proteins. In conclusion, piperine showed a potent anti-diarrheal effect in castor oil-induced diarrheal chicks by suppressing the inflammation and calcium ion influx induced by castor oil.


Assuntos
Alcaloides , Benzodioxóis , Bismuto , Loperamida , Compostos Organometálicos , Piperidinas , Alcamidas Poli-Insaturadas , Salicilatos , Humanos , Loperamida/efeitos adversos , Antidiarreicos/farmacologia , Óleo de Rícino/efeitos adversos , Nifedipino , Simulação de Acoplamento Molecular , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Diarreia/metabolismo , Alcaloides/efeitos adversos , Inflamação/tratamento farmacológico
7.
J Vis Exp ; (201)2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-38047561

RESUMO

To study human gastrointestinal physiology, biomedical scientists have relied on the use of model organisms. Although many researchers have used mice as a model to study intestinal function, only a few reports have focused on Drosophila melanogaster (D. melanogaster). Compared to mice, fruit flies present many advantages, such as a short life cycle, cost-effective and simple maintenance, and no ethical issues. Furthermore, the mammalian gastrointestinal physiology, anatomy, and signaling pathways are highly conserved in D. melanogaster. Plant extracts have been used traditionally to treat diarrhea and constipation. For example, Psidium guajava (P. guajava) is one of the most known antidiarrheal agents in the tropics. However, no studies have evaluated the effect of antidiarrheal and laxative drugs and plant extracts in D. melanogaster, and it remains unknown if similar effects (e.g., smaller, more concentrated, and less abundant fecal deposits in the case of antidiarrheal drugs) can occur in the fruit flies compared to mammals. In this study, an antidiarrheal effect induced by P. guajava is demonstrated in a D. melanogaster strain that presents a diarrheic phenotype. Fecal sampling produced by flies is monitored using a dye-supplemented food. This protocol outlines the method used for preparing food with drugs, evaluating the fecal deposits of flies fed on these food preparations, and interpreting the data obtained.


Assuntos
Antidiarreicos , Extratos Vegetais , Animais , Antidiarreicos/farmacologia , Diarreia/tratamento farmacológico , Drosophila melanogaster , Extratos Vegetais/farmacologia
8.
Microb Pathog ; 184: 106380, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37821049

RESUMO

In developing countries, diarrhoea is a major issue of concern, where consistent use of antibiotics has resulted in several side effects along with development of resistance among pathogens against these antibiotics. Since natural products are becoming the treatment of choice, therefore present investigation involves mechanistic evaluation of antidiarrhoeal potential of Begonia roxburghii and its marker rutin against Shigella flexneri (SF) induced diarrhoea in rats following in vitro, in vivo and in silico protocols. The roots of the plant are used as vegetable in the North East India and are also used traditionally in treating diarrhoea. Phytochemically standardized ethanolic extract of B. roxburghii (EBR) roots and its marker rutin were first subjected to in vitro antibacterial evaluation against SF. Diarrhoea was induced in rats using suspension of SF and various diarrhoeagenic parameters were examined after first, third and fifth day of treatment at 100, 200 and 300 mg/kg, p.o. with EBR and 50 mg/kg, p.o. with rutin respectively. Additionally, density of SF in stools, stool water content, haematological and biochemical parameters, cytokine profiling, ion concentration, histopathology and Na+/K+-ATPase activity were also performed. Molecular docking and dynamics simulation studies of ligand rutin was studied against secreted extracellular protein A (Sep A, PDB: 5J44) from SF and Inducible nitric oxide synthase (iNOS, PDB: 1DD7) followed by network pharmacology. EBR and rutin demonstrated a potent antibacterial activity against SF and also showed significant recovery from diarrhoea (EBR: 81.29 ± 0.91% and rutin: 75.27 ± 0.89%) in rats after five days of treatment. EBR and rutin also showed significant decline in SF density in stools, decreased cytokine expression, potential antioxidant activity, cellular proliferative nature and recovered ion loss due to enhanced Na+/K+-ATPase activity, which was also supported by histopathology. Rutin showed a very high docking score of -11.61 and -9.98 kcal/mol against iNOS and Sep A respectively and their stable complex was also confirmed through dynamics, while network pharmacology suggested that, rutin is quite capable of modulating the pathways of iNOS and Sep A. Thus, we may presume that rutin played a key role in the observed antidiarrhoeal activity of B. roxburghii against SF induced diarrhoea.


Assuntos
Begoniaceae , Rutina , Ratos , Animais , Rutina/farmacologia , Rutina/uso terapêutico , Shigella flexneri , Begoniaceae/metabolismo , Antidiarreicos/uso terapêutico , Óxido Nítrico Sintase Tipo II/metabolismo , Simulação de Acoplamento Molecular , Diarreia/tratamento farmacológico , Diarreia/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Citocinas/metabolismo , Adenosina Trifosfatases/metabolismo
9.
J Am Vet Med Assoc ; 261(12): 1853-1861, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37669749

RESUMO

Objective: To characterize clinician preferences and justification for preferred methods for managing canine idiopathic acute diarrhea (IAD) and compare results to evidence-based literature. sample: 284 surveys from veterinarians in small animal first-opinion practice. Methods: Veterinarians were asked to complete a survey (61 questions) including background demographic information, practice type and location, duration in practice, and management questions for canine IAD pertaining to nutritional, probiotic, antimicrobial, antidiarrheal, benign neglect, and other therapies. The survey was available between May 5, 2021, and August 30, 2021. Results: Respondents reported that their preferred first-line therapy for canine IAD included dietary modification (41.3% of respondents), probiotics (20.1%), antimicrobials (21.2%), antidiarrheal medications (13.0%), and benign neglect (4.3%). The percentage of respondents who reported each therapy as either extremely effective or very effective for canine IAD varied by treatment, as follows: antimicrobials (75.2%), dietary modification (59.13%), antidiarrheal medications (42.5%), probiotics (35.5%), and benign neglect (6.52%). Perceptions of effectiveness, efficiency of treatment, and clinician justification for use were variable among treatments. Reported practice styles were occasionally in disagreement with evidence-based methods of canine IAD management. Clinical Relevance: Current clinical management of IAD is not consistently in agreement with evidence-based recommendations. The results of this study underscore the continued need to evaluate veterinary prescribing practice trends compared to evidence-based recommendations and promote dissemination of new information.


Assuntos
Antibacterianos , Médicos Veterinários , Animais , Cães , Humanos , Antibacterianos/uso terapêutico , Antidiarreicos/uso terapêutico , Inquéritos e Questionários , Diarreia/tratamento farmacológico , Diarreia/veterinária
10.
Pharm. pract. (Granada, Internet) ; 21(3): 1-4, jul.-sep. 2023. tab
Artigo em Inglês | IBECS | ID: ibc-226161

RESUMO

Introduction: Acute gastroenteritis is a clinical syndrome often defined by increased stool frequency (eg, ≥3 loose or watery stools in 24 hours, also it is one of the most common causes of morbidity and mortality in children under 5 years in the developing world. Racecadotril is an antisecretory agent that can prevent fluid/electrolyte depletion from the bowel as a result of acute diarrhea without affecting intestinal motility. Research question or hypothesis: To investigate whether prescribing Racecadotril plus oral rehydrating solution in outpatient care helps to decrease the hospital revisit rate within 72 hours due to acute gastroenteritis in comparison with oral rehydrating solution alone. Study design: Retrospective cohort study. Methods: Pediatric patients aged 3 months to 14 years visited Al Wakra Pediatric emergency department due to acute gastroenteritis for outpatient care in the period between 1/1/2022 till 30/06/2022 were included. Case group was defined as patients who prescribed oral rehydrating solution plus Racecadotril upon their initial visit. Control group was defined as patients who prescribed only oral rehydrating solution upon their initial visit. Results: 2505 pediatric patients were included, 520 patients were enrolled in the control group, and 1985 patients were included in the case group. Most patients in both groups were 1 to 5 years old (67% in control group, and 59% in case group). The hospital revisit rate within 72 hours due to gastroenteritis was slightly less in case group 7.1% in comparison with 7.5% in control group (Relative risk 0.95, 95% CI 0.68 to 1.34). Most patients (88%) who revisited the hospital due to gastroenteritis within 72 hours showed no or mild signs of clinical dehydration in their initial visit (77% in control group, and 93% in case group) Conclusion: Racecadotril was found to have insignificant impact on hospital revisit rate in acute pediatric gastroenteritis managed at outpatient setting. (AU)


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Gastroenterite/tratamento farmacológico , Assistência Ambulatorial , Visita a Consultório Médico , Antidiarreicos/uso terapêutico , Estudos Retrospectivos , Estudos de Coortes , Catar , Soluções para Reidratação/uso terapêutico , Antidiarreicos/efeitos adversos
11.
Ann Surg Oncol ; 30(12): 7236-7239, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37626252

RESUMO

INTRODUCTION: After extensive small and colon resections, quality of life can be affected. We propose the antiperistaltic transverse coloplasty as a solution that allows for preservation of the transverse colon after both right and left colectomies while achieving a tension-free colorectal anastomosis slowing the transit and increasing the absorption time, resulting in better stool consistency and quality of life compared with an ileorectal anastomosis. METHODS: This technique was performed in a 41-year-old woman with Goblet cell adenocarcinoma of the appendix with peritoneal metastasis. The transverse colon is rotated anticlockwise over the axis of the middle colic vessels toward the left parietocolic flank and relocated to the usual position of the descending colon. RESULTS: After 1 year of follow-up, the patient led a normal life without parenteral nutrition with five bowel movements per day and a weight gain of 15%. CONCLUSIONS: The use of an antiperistaltic transverse coloplasty may be worthwhile to perform in cases of extensive bowel resections during cytoreductive surgery leading to short-bowel syndrome to avoid a permanent stoma or intestinal failure and improve patient outcomes.


Assuntos
Neoplasias Colorretais , Insuficiência Intestinal , Feminino , Humanos , Adulto , Colo/cirurgia , Antidiarreicos , Qualidade de Vida , Colectomia/métodos , Anastomose Cirúrgica/métodos , Neoplasias Colorretais/cirurgia , Resultado do Tratamento
12.
Drug Des Devel Ther ; 17: 2355-2368, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37588013

RESUMO

Purpose: In China, herbal preparation is commonly administered transdermally for treating pediatric diarrhea. However, few studies have probed into their antidiarrheal mechanisms. This study was designed to investigate the antidiarrheal effect of Renzhu ointment (Renzhuqigao, RZQG) and its underlying mechanisms via transdermal administration. Methods: The main components of RZQG were confirmed by gas chromatography-mass spectrometry (GC-MS). The effect of RZQG on L-type voltage-dependent calcium channel (L-VDCC) was evaluated by CaCl2- and ACh-induced contraction in isolated colon. The antidiarrheal efficacy of RZQG was further investigated by the senna-induced diarrhea mice based on the frequency of loose stools, diarrhea rate and index, fecal moisture content, and the basal tension of the colon. Additionally, the protein expression of CACNA1C, CACNA1D, cAMP, and PKA were detected with Western blot and immunohistochemistry (IHC). Results: GC-MS analysis determined 14 components in RZQG. In vitro, RZQG relaxed the CaCl2- and ACh-induced tension, while nifedipine (a L-VDCC inhibitor) and H-89 (a PKA inhibitor) decreased the relaxation. In vivo, animal model showed that transdermal administration of RZQG exhibited a significant reduction in the frequency of loose stools, diarrhea rate and index, fecal moisture content and the basal tension. Compared to the model group, the colon of mice treated with RZQG showed lower expression of CACNA1C, CACNA1D, cAMP, and PKA. IHC results showed that cAMP was downregulated in colonic smooth muscle after RZQG treatment. Conclusion: RZQG improved diarrhea symptoms and down-regulated the expression of CACNA1C and CACNA1D via transdermal administration, which is closely associated with the cAMP/PKA signaling pathway in colonic smooth muscle.


Assuntos
Antidiarreicos , Canais de Cálcio Tipo L , Animais , Camundongos , Administração Cutânea , Antidiarreicos/farmacologia , Cloreto de Cálcio , Pomadas , Senosídeos , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Fármacos Gastrointestinais , Modelos Animais de Doenças
13.
Artigo em Inglês | MEDLINE | ID: mdl-37510632

RESUMO

This study aimed to assess the ability of community pharmacists to recognize cases of loperamide abuse at the point of sale, their perspective of and experience toward potential abuse cases. METHODS: A cross-sectional study was conducted in Jordan, using a self-administered online questionnaire. The questionnaire consisted of three main parts: demographics, the experience of pharmacists with abusers' behavior, as well as their perspectives toward loperamide abuse. RESULTS: A total of 250 community pharmacists completed the survey, 54% (135) of which were female. Almost one-third (33.2%; 83) of the participants reported exposure to suspected cases of loperamide abuse during the last six months. Pharmacists declared that most of the suspected loperamide abusers were male (60.2%), of middle-low socioeconomic status (69.9%), and between 20 and 30 years of age (57.8%). The largest quantity (packs) of loperamide requested by a single patient was around 33.2 ± 14.9 at once. As reported by pharmacists, the suspected reasons behind loperamide abuse included 50% seeking euphoria, 17% relieving anxiety, and 33% controlling addiction (weaning off other opioids). The multivariate logistic regression analysis demonstrated a significant correlation between the male sex (OR = 1.2, 95% CI 0.12-1.59), pharmacy location in the center of Jordan (OR = 21.2, 95% CI 2.45-183.59), late-night working shift (Shift C, OR = 1.29, 95% CI 0.12-2.08), and abuse to loperamide during the last six months. CONCLUSIONS: This study sheds light on loperamide abuse potentials, which could be influenced by different sociodemographic characteristics. Accordingly, close monitoring and thorough tackling of the abuse practices are mandated through an increase in educational and awareness campaigns about proper medication use.


Assuntos
Loperamida , Transtornos Relacionados ao Uso de Substâncias , Humanos , Masculino , Feminino , Loperamida/uso terapêutico , Antidiarreicos , Farmacêuticos , Estudos Transversais , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
14.
NPJ Biofilms Microbiomes ; 9(1): 33, 2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-37280255

RESUMO

The diarrheal disease causes high mortality, especially in children and young animals. The gut microbiome is strongly associated with diarrheal disease, and some specific strains of bacteria have demonstrated antidiarrheal effects. However, the antidiarrheal mechanisms of probiotic strains have not been elucidated. Here, we used neonatal piglets as a translational model and found that gut microbiota dysbiosis observed in diarrheal piglets was mainly characterized by a deficiency of Lactobacillus, an abundance of Escherichia coli, and enriched lipopolysaccharide biosynthesis. Limosilactobacillus mucosae and Limosilactobacillus reuteri were a signature bacterium that differentiated healthy and diarrheal piglets. Germ-free (GF) mice transplanted with fecal microbiota from diarrheal piglets reproduced diarrheal disease symptoms. Administration of Limosilactobacillus mucosae but not Limosilactobacillus reuteri alleviated diarrheal disease symptoms induced by fecal microbiota of diarrheal piglets and by ETEC K88 challenge. Notably, Limosilactobacillus mucosae-derived extracellular vesicles alleviated diarrheal disease symptoms caused by ETEC K88 by regulating macrophage phenotypes. Macrophage elimination experiments demonstrated that the extracellular vesicles alleviated diarrheal disease symptoms in a macrophage-dependent manner. Our findings provide insights into the pathogenesis of diarrheal disease from the perspective of intestinal microbiota and the development of probiotic-based antidiarrheal therapeutic strategies.


Assuntos
Antidiarreicos , Microbiota , Animais , Suínos , Camundongos , Diarreia/veterinária , Lactobacillus , Bactérias , Escherichia coli , Homeostase
15.
J Ethnopharmacol ; 317: 116696, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37315649

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Rosa webbiana (Family: Rosaceae) is used by South Asian herbalists to treat gastrointestinal and respiratory disorders. AIM OF THE STUDY: This research aimed at multiple targets to verify R. webbiana for treating diarrhea and asthma. In vitro, in vivo, and in silico experiments were planned to demonstrate the antispasmodic and bronchodilator potential of R. webbiana. MATERIALS AND METHODS: The bioactive compounds of R. webbiana were identified and quantified through LC ESI-MS/MS and HPLC. These compounds were predicted for muti-mechanisms of bronchodilator and antispasmodic potential in network pharmacology and molecular docking. In vitro methods (isolated rabbit trachea, bladder, and jejunum tissues) confirmed these multi-mechanisms for antispasmodic and bronchodilator effects. Antiperistalsis, antidiarrheal, and antisecretory experiments were conducted in in-vivo experiments. RESULTS: The phytochemical analysis indicates the presence of rutin (742.91 µg/g), kaempferol (726.32 µg/g), and quercitrin (688.20 µg/g) in Rw. EtOH. These bioactive compounds in network pharmacology interfere with the pathogenic genes of diarrhea and asthma, which are the members of calcium-mediated signaling pathways and showed the stronger binding affinity towards voltage-gated L-type calcium channels, myosin light chain-kinase, Calcium calmodulin-dependent-kinase, Phosphodiesterase-4, and phosphoinositide phospholipase-C in molecular docking. Rw. EtOH elicited a spasmolytic response in isolated jejunum, trachea, and urine preparations by relaxing K+ (80 mM) and CCh (1 µM) spastic contractions. Additionally, it suppressed calcium concentration-response curves to the right, like verapamil. Like dicyclomine, it caused a rightward parallel shift of the CCh curves, followed by a non-parallel shift at higher concentrations with suppression of the maximal response. Like papaverine, it also caused isoprenaline-induced inhibitory CRCs to shift to the left. Verapamil did not potentiate isoprenaline-induced inhibitory CRCs, although it was more efficacious against K+ (80 mM) than CCh (1 µM)-induced contractions. R. webbiana EtOH extract exhibited complete antiperistalsis (21.55%), antidiarrheal (80.33%), and antisecretory (82.59±0.60) activities in vivo experiments at the dose of 300 mg/kg. CONCLUSION: Thus, Rw. EtOH modulated multiple pathways, produced calcium antagonistic, anticholinergic, and phosphodiesterase inhibitory actions, and had antidiarrheal and bronchodilator effects.


Assuntos
Asma , Rosa , Animais , Coelhos , Antidiarreicos/farmacologia , Antidiarreicos/uso terapêutico , Antidiarreicos/química , Parassimpatolíticos/uso terapêutico , Broncodilatadores/farmacologia , Isoproterenol , Simulação de Acoplamento Molecular , Cálcio/metabolismo , Estudos Prospectivos , Espectrometria de Massas em Tandem , Extratos Vegetais/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Verapamil/farmacologia , Jejuno , Fármacos Gastrointestinais/farmacologia , Canais de Cálcio , Asma/tratamento farmacológico
16.
J Ethnopharmacol ; 316: 116705, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37301303

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Psydrax schimperianus (A. Rich.) Bridson. roots are used for the treatment of diarrhea in West Arsi zone, Ethiopia. AIM OF THE STUDY: This study aimed to investigate the in vivo antidiarrheal activity of crude extract and coumarins isolated from the roots of Psydrax schimperianus to provide a pharmacological basis for its traditional use as an antidiarrheal agent in Ethiopia. MATERIALS AND METHODS: The crude root extract of P. schimperianus was tested in vivo for antidiarrheal efficacy in mice utilizing castor oil-induced diarrhea, gastrointestinal transit time, and enteropooling models at doses of 100, 200, and 400 mg/kg. Phytochemical investigation of the crude root extract led to the isolation of two coumarins, isoscopoletin, and scoparone. Isoscopoletin and scoparone were evaluated for antidiarrheal activity against castor oil-induced diarrhea model at 10 mg/kg and 20 mg/kg doses. RESULTS: The crude root extract of P. schimperianus, at doses of 100, 200, and 400 mg/kg, inhibited defecation by 37.5%, 46.2%, and 61.2%, respectively. At a dose of 20 mg/kg, scoparone and isoscopoletin reduced defecation by 61.2% and 66.6%, respectively. CONCLUSION: The study warrants further investigation of isoscopoletin and scoparone towards development as a novel treatment for diarrheal diseases.


Assuntos
Antidiarreicos , Óleo de Rícino , Camundongos , Animais , Antidiarreicos/farmacologia , Antidiarreicos/uso terapêutico , Extratos Vegetais/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Cumarínicos/farmacologia , Cumarínicos/uso terapêutico
17.
Updates Surg ; 75(4): 871-880, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36914915

RESUMO

To investigate the clinical efficacy of laparoscopic total colectomy with ileorectal anastomosis (TC-IRA) and laparoscopic subtotal colectomy with antiperistaltic cecorectal anastomosis (SC-ACRA) on adults with slow transit constipation (STC). One hundred and three patients with STC were assigned to the TC-IRA group (n = 53) and the SC-ACRA group (n = 50). The clinical data were analyzed. The surgery was successful in all patients (100%). Significantly (P = 0.03) more patients took anti-laxatives during hospitalization in the TC-IRA than the SC-ACRA group (39.62% vs. 20.00%). Abdominal pain and distension was present in 33.96% and 32.00% patients in the TC-IRA and SC-ACRA group, respectively, which decreased insignificantly (P > 0.05) to 18.87% and 18.00% 24 months after surgery, respectively. The postoperative Wexner and gastrointestinal quality of life (GIQLI) scores were not significantly different (P > 0.05) at all times after surgery in both groups. The defecation frequency decreased in both groups, and the average defecation frequency was significantly (P < 0.05) higher in the TC-IRA than the SC-ACRA group (3.91 ± 1.23 vs. 3.14 ± 1.15 times/day) at 3 months. Three months after surgery, significantly (P < 0.05) fewer patients were satisfied with defecation frequency in the TC-IRA than the SC-ACRA group (29 vs. 37 patients), whereas the number of patients who were willing to choose the same procedure again was not significantly (P > 0.05) different between the two groups. The WIS score of patients was significantly (P = 0.035) higher in the TC-IRA than the SC-ACRA group (6 vs. 5) 3 months later. TC-IRA and SC-ACRA are both safe and effective for adult slow transit constipation, and can significantly improve the quality of life of patients. Even though SC-ACRA has better early defecation frequency, postoperative antidiarrheal application and satisfaction, the long-term follow-up effects are similar.


Assuntos
Antidiarreicos , Laparoscopia , Adulto , Humanos , Qualidade de Vida , Ceco/cirurgia , Constipação Intestinal/cirurgia , Reto/cirurgia , Colectomia/métodos , Resultado do Tratamento , Anastomose Cirúrgica/métodos
18.
Anal Biochem ; 668: 115116, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36925055

RESUMO

Acute enteritis (AE) is a type of digestive disease caused by biochemical factors that irritate the intestinal tract or pathogenic bacteria that infect it. In China, Ma-Mu-Ran Antidiarrheal Capsules (MMRAC) have been applied against diarrhea caused by AE and bacillary dysentery for many years, but the underlying mechanisms of their beneficial effects are not known. In the present study, network pharmacology and metabolomics were performed to clarify the active ingredients of MMRAC and explore the specific mechanism of MMRAC on AE mice. A total of 43 active components of MMRAC with 87 anti-AE target genes were identified, and these target genes were enriched in IL-17 and HIF-1 signaling pathways. Integration analysis revealed that purine metabolism was the critical metabolic pathway by which MMRAC exerted its therapeutic effect against AE. Specifically, MAPK14, MMP9, PTGS2, HIF1A, EGLN1, NOS2 were the pivotal targets of MMRAC for the treatment of AE, and Western blot analysis revealed MMRAC to decrease protein levels of these pro-inflammatory signaling molecules. According to molecular docking, these key targets have a strong affinity with the MMRAC compounds. Collectively, MMRAC relieved the colon inflammation of AE mice via regulating inflammatory signaling pathways to reduce hypoxia and improved energy metabolism.


Assuntos
Medicamentos de Ervas Chinesas , Enterite , Animais , Camundongos , Antidiarreicos/farmacologia , Antidiarreicos/uso terapêutico , Farmacologia em Rede , Simulação de Acoplamento Molecular , Metabolômica , Enterite/tratamento farmacológico , Cápsulas , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
19.
Lakartidningen ; 1202023 03 22.
Artigo em Sueco | MEDLINE | ID: mdl-36994929

RESUMO

The basic principle for treatment of idiopathic diarrhea is to delay transit through the gut in order to promote absorption of electrolytes and water. Under mild conditions bulking agents may suffice. With increasing severity, antidiarrheal pharmaceuticals may be added in a stepwise manner. Bile salt malabsorption is a clear indication for adsorptive resins, while in idiopathic diarrhea peripherally-acting opioid receptor agonists, such as loperamide, is the first-line treatment. Second-line treatment with approved indication for severe diarrhea when other treatment options fail includes opium drops. More advanced treatments are to be used by clinicians with specialist knowledge and experience in the field.


Assuntos
Antidiarreicos , Diarreia , Humanos , Diarreia/tratamento farmacológico , Antidiarreicos/uso terapêutico , Loperamida/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico
20.
Pak J Pharm Sci ; 36(1): 17-22, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36967492

RESUMO

Platanus orientalis is traditionally used to treat diarrhea and spasm. However, studies are lacking on its mechanism of action in diarrhea and spasm. Pharmacological in-vivo activities were performed. In-vitro activities were carried out to explore the underlying mechanism(s) of action in isolated tissue preparations of mice jejunum and ileum. Crude extract of Platanus orientalis, loperamide and verapamil were used. The crude extract provided dose-dependent protection in castor oil diarrhea like verapamil and reduced the intestinal fluid accumulation and charcoal meal transit distance. In-vitro studies produced spasmolytic effect on the spontaneous (EC50 value=0.21mg/mL), high K+ (EC50 value=0.37mg/mL) and carbachol (CCh)-induced contractions 5.35mg/mL (3.88-6.85) respectively. The quiescent ileum responded well to the high K+ and carbachol (CCh)-induced contractions when tested against crude extract. It caused inhibition of the induced contraction with EC50 values of 0.20mg/mL (0.10-0.30) and 3.25mg/mL (2-4.5) respectively and showed potent effect against CCh-induced contractions. Calcium response curves produced a similar effect to verapamil. The crude extract of Platanus orientalis remained safe up to 5g/kg dose.


Assuntos
Antidiarreicos , Extratos Vegetais , Camundongos , Animais , Antidiarreicos/farmacologia , Antidiarreicos/uso terapêutico , Carbacol/farmacologia , Extratos Vegetais/uso terapêutico , Jejuno , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Parassimpatolíticos/farmacologia , Verapamil/farmacologia , Músculo Liso , Espasmo/tratamento farmacológico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...