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1.
J Immunol Res ; 2022: 4126273, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35345778

RESUMO

American ginseng (Panax quinquefolius L.) is an herbal medicine with polysaccharides as its important active ingredient. The purpose of this research was to identify the effects of the polysaccharides of P. quinquefolius (WQP) on rats with antibiotic-associated diarrhoea (AAD) induced by lincomycin hydrochloride. WQP was primarily composed of galacturonic acid, glucose, galactose, and arabinose. The yield, total sugar content, uronic acid content, and protein content were 6.71%, 85.2%, 31.9%, and 2.1%, respectively. WQP reduced the infiltration of inflammatory cells into the ileum and colon, reduced the IL-1ß, IL-6, IL-17A, and TNF-α levels, increased the levels of IL-4 and IL-10 in colon tissues, improved the production of acetate and propionate, regulated the gut microbiota diversity and composition, improved the relative richness of Lactobacillus and Bacteroides, and reduced the relative richness of Blautia and Coprococcus. The results indicated that WQP can enhance the recovery of the intestinal structure in rats, reduce inflammatory cytokine levels, improve short-chain fatty acid (SCFA) levels, promote recovery of the gut microbiota and intestinal mucosal barrier, and alleviate antibiotic-related side effects such as diarrhoea and microbiota dysbiosis caused by lincomycin hydrochloride. We found that WQP can protect the intestinal barrier by increasing Occludin and Claudin-1 expression. In addition, WQP inhibited the MAPK inflammatory signaling pathway to improve the inflammatory status. This study provides a foundation for the treatment of natural polysaccharides to reduce antibiotic-related side effects.


Assuntos
Panax , Animais , Antibacterianos/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Diarreia/metabolismo , Lincomicina/farmacologia , Lincomicina/uso terapêutico , Sistema de Sinalização das MAP Quinases , Panax/química , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Ratos
2.
Acta Cir Bras ; 37(2): e370204, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35507968

RESUMO

PURPOSE: To evaluate the protective effect of Cuscuta chinensis Lam. polysaccharides (PCCL) on 5-fluorouracil-(5-FU)-induced intestinal mucositis (IM) in mice. METHODS: PCCL was orally administered at a dose of 20 mg·kg-1 for 7 days and its protective effect on 5-FU-induced IM (5-FU, 50 mg·kg-1 for 5 days) was evaluated by monitoring changes in body weight, degree of diarrhea, levels of tissue inflammatory factors (tumor necrosis factor α, interleukin 6, and interleukin 1ß levels), apoptosis rates, and the expression levels of caspase-3, Bax and Bcl-2. RESULTS: The severity of mucosal injury (as reflected by body weight changes, degree of diarrhea, height of villi, and damage to crypts) was significantly attenuated by PCCL administration. PCCL also reduced the levels of tissue inflammatory factors, the apoptosis rate, and the expression of caspase-3 and Bax, and increased Bcl-2 expression. CONCLUSIONS: PCCL administration may be significantly protective against 5-FU-induced IM by inhibiting apoptosis and regulating the abnormal inflammation associated with it.


Assuntos
Cuscuta , Mucosite , Animais , Antimetabólitos Antineoplásicos/efeitos adversos , Peso Corporal , Caspase 3/metabolismo , Cuscuta/metabolismo , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Diarreia/patologia , Fluoruracila/efeitos adversos , Mucosa Intestinal/patologia , Camundongos , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Mucosite/prevenção & controle , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Sementes , Proteína X Associada a bcl-2/metabolismo
3.
Biomed Res Int ; 2022: 1331758, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35528171

RESUMO

Hoya parasitica (Wall.) is extensively used in traditional medicine for the treatment of various diseases including rheumatism, kidney problems, jaundice, urinary tract disorders, fever, and pain. The present study was designed to explore new lead compound(s) to alleviate pain, pyresis, and diarrhea from methanol, ethyl acetate, and n-hexane extracts of H. parasitica (Wall.) leaves (MHP, EAHP, and NHP, respectively). Analgesic activity of the extracts was assessed through acetic acid induced writhing, tail immersion, and hot plate tests while brewer's yeast-induced pyrexia test was employed for the assessment of antipyretic activity. Besides, castor oil and magnesium sulfate induced diarrheal tests were utilized for the evaluation of antidiarrheal properties. Moreover, in silico study of the isolated compounds was undertaken to seek out best-fit phytoconstituent(s) against cyclooxygenase enzymes. MHP revealed substantial antioxidant activities in different in vitro assays compared to EAHP and NHP. In the acetic acid-induced writhing test, among the extracts, MHP (400 mg/kg) revealed maximum 74.15 ± 1% inhibition of writhing comparable to that of standard (85.77 ± 1.39%). Again, in tail immersion and hot plate tests, higher doses of all the test samples exhibited a significant increase of latent period in a time-dependent manner. In brewer yeast-induced pyrexia test, at 3rd and 4th hour of treatment, significant (P < 0.05) antipyretic action was found in the test samples. In both castor oil and magnesium induced diarrheal tests, MHP at 400 mg/kg showed the highest percent inhibition of diarrhea (68.62 ± 4.74 and 64.99 ± 2.90, respectively). Moreover, molecular docking analysis corroborated the results of the present study. The findings of the present study supported the traditional uses of this plant for the alleviation of pain and fever. Furthermore, hoyasterone was found to be the most effective lead compound as cyclooxygenase enzyme inhibitor.


Assuntos
Antipiréticos , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Antipiréticos/farmacologia , Óleo de Rícino/efeitos adversos , Ciclo-Oxigenase 2 , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Febre , Humanos , Simulação de Acoplamento Molecular , Dor/tratamento farmacológico , Extratos Vegetais/uso terapêutico
4.
Am J Case Rep ; 23: e935730, 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-35431313

RESUMO

BACKGROUND Metformin-associated lactic acidosis (MALA) is a relatively rare adverse effect of metformin therapy. It usually occurs in patients with metformin overdose or in those with underlying acute and/or chronic conditions resulting in impaired lactate metabolism. Among these, patients with acute kidney injury, heart failure, sepsis, and cirrhosis are the most vulnerable to MALA, even in the setting of appropriate therapy. The most common symptoms of MALA include nausea, vomiting, diarrhea, encephalopathy, hypothermia, respiratory failure, and hypotension. Blindness is a dramatic symptom that has been rarely reported with MALA. CASE REPORT We report a case of 78-year-old woman with history of type 2 diabetes mellitus with nephropathy for which she was treated with metformin and insulin. She developed nausea, non-bloody emesis, and watery diarrhea, which led to dehydration, anion gap metabolic acidosis due to hyperlactatemia, and acute kidney injury (AKI). She was hospitalized for i.v. hydration and further management when she suddenly developed blindness. The diagnostic work-up ruled out central causes and her symptoms resolved briefly after continuous renal replacement therapy (CRRT) was initiated, confirming the diagnosis of MALA. CONCLUSIONS By reporting this case, we wish to increase awareness about MALA symptoms, its diagnosis, and the importance of early recognition and initiation of treatment among clinicians involved in the care of patients with chronic kidney disease (CKD) who take metformin for diabetes mellitus. Although rare, this metformin adverse effect can present dramatically and can be distressing for both patient and treating team.


Assuntos
Acidose Láctica , Injúria Renal Aguda , Diabetes Mellitus Tipo 2 , Metformina , Acidose Láctica/induzido quimicamente , Acidose Láctica/terapia , Injúria Renal Aguda/induzido quimicamente , Idoso , Cegueira/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diarreia/induzido quimicamente , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Masculino , Metformina/efeitos adversos , Náusea , Diálise Renal/efeitos adversos
5.
J Int Assoc Provid AIDS Care ; 21: 23259582221088202, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35466761

RESUMO

Gastrointestinal intolerance has been associated with ritonavir-boosted protease inhibitors. This post hoc analysis evaluated gastrointestinal adverse events of interest (AEOIs; diarrhea, nausea, abdominal discomfort, flatulence [MedDRAv21]) through Wk96 among patients enrolled in the phase 3 AMBER (treatment-naïve) and EMERALD (virologically suppressed) studies of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg. 362 and 763 patients initiated D/C/F/TAF in AMBER and EMERALD, respectively. All D/C/F/TAF-related gastrointestinal AEOIs were grade 1/2 in severity; none were serious. Across studies, incidence of D/C/F/TAF-related diarrhea and nausea were each ≤5% in Wk1 (≤1% post-Wk2); prevalence of each decreased to <5% post-Wk2. In each study, there was 1 case of D/C/F/TAF-related abdominal discomfort during Wk1 and none thereafter. Incidence of D/C/F/TAF-related flatulence was <1% throughout. Median duration of D/C/F/TAF-related gastrointestinal AEOIs was 16.5 (AMBER) and 8.5 (EMERALD) days. In conclusion, in treatment-naïve and virologically suppressed patients, incidences and prevalences of D/C/F/TAF-related gastrointestinal AEOIs were low and tended to present early.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Alanina , Fármacos Anti-HIV/efeitos adversos , Cobicistat/efeitos adversos , Darunavir/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/epidemiologia , Emtricitabina/efeitos adversos , Flatulência/induzido quimicamente , Flatulência/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Humanos , Incidência , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Tenofovir/análogos & derivados
6.
Chem Biol Interact ; 360: 109946, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35430260

RESUMO

Irinotecan, a first-line chemotherapy for gastrointestinal (GI) cancers has been causing fatal toxicities like bloody diarrhea and steatohepatitis for years. Irinotecan goes through multiple-step drug metabolism after injection and one of its intermediates 7-ethyl-10-hydroxy-camptothecin (SN-38) is responsible for irinotecan side effect. However, it is unclear what is the disposition kinetics of SN-38 in the organs subjected to toxicity. No studies ever quantified the effect of each enzyme or transporter on SN-38 distribution. In current study, we established a new physiologically based pharmacokinetic (PBPK) model to predict the disposition kinetics of irinotecan. The PBPK model was calibrated with in-house mouse pharmacokinetic data and evaluated with external datasets from the literature. We separated the contribution of each parameters in irinotecan pharmacokinetics by calculating the normalized sensitivity coefficient (NSC). The model gave robust prediction of SN-38 distribution in GI tract, the site of injury. We identified that bile excretion and UDP-glucuronosyltransferases (UGT) played more important roles than fecal excretion and renal clearance in SN-38 pharmacokinetics. Our NSC showed that the impact of enzyme and transporter on irinotecan and SN-38 pharmacokinetics evolved when time continued. Additionally, we mapped out the effect of inflammation on irinotecan metabolic pathways with PBPK modelling. We discovered that inflammation significantly increased the blood and liver exposure of irinotecan and SN-38 in the mice receiving bacterial endotoxin. Inflammation suppressed UGT, microbial metabolism but increased fecal excretion. The present PBPK model can serve as an efficacious and versatile tool to quantitively assess the risk of irinotecan toxicity.


Assuntos
Antineoplásicos Fitogênicos , Camptotecina , Animais , Antineoplásicos Fitogênicos/toxicidade , Camptotecina/efeitos adversos , Diarreia/induzido quimicamente , Glucuronosiltransferase/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Irinotecano , Camundongos
7.
BMJ Case Rep ; 15(4)2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35473697

RESUMO

Congenital chloride losing diarrhoea (CCLD) is a rare disease caused by mutations in an intestinal chloride/bicarbonate ion exchange channel. Few reports describe CCLD in adults and none has described the impact of a parasitic infection on CCLD. Severe diarrhoea may result in hypokalaemia with QT interval prolongation. Treatment with antiemetics may further increase the QT interval. To raise awareness of this preventable complication, we describe the course of a woman in her 20s with CCLD who developed COVID-19 and a Blastocystis hominis infestation. Treatment with antiemetics and hypokalaemia resulted in prolongation of the QT interval to 640 ms. While, the QT interval normalised with discontinuation of antiemetics and electrolyte replacement, patients with CCLD must take precautions to prevent gastrointestinal infections. Regardless, whenever patients with CCLD present to hospital, the authors recommend monitoring the QT interval and avoiding medications that predispose to torsade de pointes.


Assuntos
Antieméticos , Blastocystis hominis , COVID-19 , Hipopotassemia , Síndrome do QT Longo , Adulto , COVID-19/tratamento farmacológico , Cloretos , Diarreia/induzido quimicamente , Diarreia/complicações , Diarreia/congênito , Diarreia/tratamento farmacológico , Eletrocardiografia , Feminino , Humanos , Hipopotassemia/complicações , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/tratamento farmacológico , Erros Inatos do Metabolismo
8.
BMC Cancer ; 22(1): 371, 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35392858

RESUMO

BACKGROUND: Toxicity during chemoradiotherapy (CRT) in cervical cancer patients might limit the chances of receiving an optimal treatment and to be cured. Few studies have shown relationships between acute side effects and patient's age. Here, the association between age and acute side effects such as nausea/vomiting, diarrhea and weight loss during CRT was analysed in cervical cancer patients. METHODS: This study included 93 patients with primary cervical cancer stage IBI to IVA who received CRT from 2013 to 2019. The frequency of symptoms/toxicity grade was analysed by using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: Patients ≥ 52 years had a significantly higher frequency of nausea/vomiting and increased grade ≥ 3 toxicity during CRT compared to younger patients (p < 0.001, p = 0.001). Toxicity grade ≥ 3 of nausea/vomiting was associated with increased frequency of weight loss (p = 0.001), reduced ADL (p = 0.001) and dose modifications of both radiotherapy (RT) (p = 0.020) and chemotherapy (CT) (p = 0.030) compared to toxicity grade 2. The frequency of diarrhea (p = 0.015) and weight loss (p = 0.020) was higher in older patients compared to younger. CONCLUSIONS: Older patients have an increased risk of acute side effects as nausea/vomiting, diarrhea and weight loss. Age could be useful in predicting acute side effects in primary cervical cancer patients with CRT.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Neoplasias do Colo do Útero , Idoso , Quimiorradioterapia/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/complicações , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Humanos , Náusea/induzido quimicamente , Náusea/epidemiologia , Neoplasias do Colo do Útero/tratamento farmacológico , Vômito/etiologia , Perda de Peso
9.
Respir Res ; 23(1): 85, 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35392908

RESUMO

BACKGROUND: In the INBUILD trial in patients with progressive fibrosing interstitial lung diseases (ILDs), nintedanib reduced the rate of decline in forced vital capacity compared with placebo, with side-effects that were manageable for most patients. We used data from the INBUILD trial to characterize further the safety and tolerability of nintedanib. METHODS: Patients with fibrosing ILDs other than idiopathic pulmonary fibrosis (IPF), who had experienced progression of ILD within the 24 months before screening despite management deemed appropriate in clinical practice, were randomized to receive nintedanib 150 mg twice daily or placebo. To manage adverse events, treatment could be interrupted or the dose reduced to 100 mg twice daily. We assessed adverse events and dose adjustments over the whole trial. RESULTS: A total of 332 patients received nintedanib and 331 received placebo. Median exposure to trial drug was 17.4 months in both treatment groups. Adverse events led to treatment discontinuation in 22.0% of patients treated with nintedanib and 14.5% of patients who received placebo. The most frequent adverse event was diarrhea, reported in 72.3% of patients in the nintedanib group and 25.7% of patients in the placebo group. Diarrhea led to treatment discontinuation in 6.3% of patients in the nintedanib group and 0.3% of the placebo group. In the nintedanib and placebo groups, respectively, 48.2% and 15.7% of patients had ≥ 1 dose reduction and/or treatment interruption. Serious adverse events were reported in 44.3% of patients in the nintedanib group and 49.5% of patients in the placebo group. The adverse event profile of nintedanib was generally consistent across subgroups based on age, sex, race and weight, but nausea, vomiting and dose reductions were more common among female than male patients. CONCLUSIONS: The adverse event profile of nintedanib in patients with progressive fibrosing ILDs other than IPF is consistent with its established safety and tolerability profile in patients with IPF and characterized mainly by gastrointestinal events, particularly diarrhea. Management of adverse events using symptomatic therapies and dose adjustment is important to minimize the impact of adverse events and help patients remain on therapy. Trial registration Registered 21 December 2016, https://clinicaltrials.gov/ct2/show/NCT02999178 A video abstract summarizing the key results presented in this manuscript is available at: https://www.globalmedcomms.com/respiratory/cottin/INBUILDsafety .


Assuntos
Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Diarreia/induzido quimicamente , Diarreia/diagnóstico , Progressão da Doença , Feminino , Humanos , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Indóis , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Masculino , Inibidores de Proteínas Quinases/uso terapêutico , Resultado do Tratamento
10.
Nat Commun ; 13(1): 2117, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35440537

RESUMO

The gut microbiota represents a large community of microorganisms that play an important role in immune regulation and maintenance of homeostasis. Living bacteria receive increasing interest as potential therapeutics for gut disorders, because they inhibit the colonization of pathogens and positively regulate the composition of bacteria in gut. However, these treatments are often accompanied by antibiotic administration targeting pathogens. In these cases, the efficacy of therapeutic bacteria is compromised by their susceptibility to antibiotics. Here, we demonstrate that a single-cell coating composed of tannic acids and ferric ions, referred to as 'nanoarmor', can protect bacteria from the action of antibiotics. The nanoarmor protects both Gram-positive and Gram-negative bacteria against six clinically relevant antibiotics. The multiple interactions between the nanoarmor and antibiotic molecules allow the antibiotics to be effectively absorbed onto the nanoarmor. Armored probiotics have shown the ability to colonize inside the gastrointestinal tracts of levofloxacin-treated rats, which significantly reduced antibiotic-associated diarrhea (AAD) resulting from the levofloxacin-treatment and improved some of the pre-inflammatory symptoms caused by AAD. This nanoarmor strategy represents a robust platform to enhance the potency of therapeutic bacteria in the gastrointestinal tracts of patients receiving antibiotics and to avoid the negative effects of antibiotics in the gastrointestinal tract.


Assuntos
Antibacterianos , Probióticos , Animais , Antibacterianos/efeitos adversos , Bactérias , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Humanos , Levofloxacino/uso terapêutico , Probióticos/uso terapêutico , Ratos
11.
Value Health ; 25(4): 566-570, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35365300

RESUMO

OBJECTIVES: Many trials conclude "no clinically meaningful detriment" to health-related quality of life (HRQL) or function between arms, even when notable differential toxicity is observed. Mean change from baseline analyses of function or HRQL can possibly obscure important change in subgroups experiencing symptomatic toxicity. We evaluate the impact of diarrhea, a key treatment arm toxicity, on patient-reported HRQL and functioning in clinical trials submitted to US Food and Drug Administration. METHODS: This study used 4 randomized, breast cancer trials (adjuvant to late-line metastatic) as case examples. Diarrhea, physical functioning (PF), and global health status and quality of life (GHS/QoL) from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 were analyzed at baseline and approximately 3 and 6 months. RESULTS: Generally, patients reporting very much diarrhea at months 3 and 6 had worse PF (9-19 points lower) and GHS/QoL (16-19 points lower) than patients reporting no diarrhea regardless of treatment arm. In the change from baseline analysis, patients reporting very much diarrhea also experienced a greater decrease in PF (6-13 points) and GHS/QoL (6-16 points) versus patients reporting no diarrhea in both arms. CONCLUSIONS: In trials with moderate to large differences in symptomatic toxicity by arm, reporting "no meaningful difference in functioning and HRQL between arms" based on mean change from baseline analysis is insufficient and may obscure important impacts on subgroups experiencing symptomatic adverse events. Additional exploratory analyses with simple data visualizations evaluating functioning or HRQL in patient subgroups experiencing expected symptomatic toxicities can further inform the safety and tolerability of an investigational agent.


Assuntos
Neoplasias da Mama , Qualidade de Vida , Neoplasias da Mama/tratamento farmacológico , Diarreia/induzido quimicamente , Feminino , Humanos , Medidas de Resultados Relatados pelo Paciente , Estados Unidos , United States Food and Drug Administration
12.
Biomed Pharmacother ; 149: 112842, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35325851

RESUMO

Anisomeles indica (L.) Kuntze is an ethnomedicinally important plant that has long been used in traditional medicine to treat a variety of ailments, including dyspepsia, abdominal pain, colic, allergies, inflammation, and rheumatic arthritis. However, the scientific framework underlying these medicinal properties is not well known. This study aimed to investigate the antidepressive, antidiarrheal, thrombolytic, and anti-inflammatory potential of a methanol extract of A. indica (MeOH-AI). The potential bioactive compounds in the MeOH-AI were identified using gas chromatography-mass spectrometry (GC-MS), and antidepressant activities were evaluated using the tail suspension test (TST) and forced swim test (FST). Antidiarrheal effects were also assayed in castor oil-induced diarrhea and gastrointestinal motility studies. The anti-inflammatory activities were explored by examining the effects on protein inhibition and denaturation in heat- and hypotonic solution-induced hemolysis assays. The thrombolytic activity was evaluated using the clot lysis test in human blood. BIOVIA and Schrödinger Maestro (v11.1) were applied for docking analysis to determine binding interactions, and the absorption, distribution, metabolisms, excretion/toxicity (ADME/T) properties of bioactive compounds were explored using a web-based method. The GC-MS analysis of MeOH-AI revealed the presence of several bioactive compounds. MeOH-AI administration resulted in significant (p < 0.01) reductions in the immobility times for both the FST and TST compared with those in the control group. MeOH-AI also induced significant (p < 0.01) reductions in castor oil-induced diarrhea severity and gastrointestinal motility in a mouse model. In addition, the in vitro anti-inflammatory and thrombolytic activity studies produced remarkable responses. The binding assay showed that 4-dehydroxy-N-(4,5-methylenedioxy-2-nitrobenzylidene) tyramine interacts favorably with monoamine oxidase and serotonin and M3 muscarinic acetylcholine receptors, displaying good pharmacokinetic properties, which may mediate the effects of MeOH-AI on depression and diarrhea. Overall, the research findings indicated that MeOH-AI has significant antidepressant, antidiarrheal, and anti-inflammatory effects and may represent an alternative source of novel therapeutic factors.


Assuntos
Antidiarreicos , Lamiaceae , Animais , Anti-Inflamatórios/uso terapêutico , Antidepressivos/farmacologia , Antidiarreicos/farmacologia , Óleo de Rícino , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Fibrinolíticos/farmacologia , Camundongos , Extratos Vegetais/uso terapêutico
13.
Expert Rev Anticancer Ther ; 22(4): 335-341, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35249433

RESUMO

INTRODUCTION: Despite rapid advances in the treatment landscape of urothelial cancer, there is a substantial unmet need for safe and effective therapies for patients with locally advanced and metastatic urothelial cancer. Sacituzumab govitecan (SG) is an antibody-drug conjugate, consisting of a Trop-2 directed monoclonal antibody linked to SN-38, the active metabolite of irinotecan. Trop-2 is a glycoprotein overexpressed in various carcinomas, including urothelial carcinomas. AREAS COVERED: We review the available data on SG, including mechanism of action, pharmacology, efficacy, safety, and clinical studies regarding locally advanced or metastatic urothelial cancer. EXPERT OPINION: SG performed well in the TROPHY-U-01 phase II trial with an objective response rate of 27%. The most common adverse effects were diarrhea, nausea, fatigue, alopecia, and neutropenia, with the most common grade ≥ 3 treatment-related AEs being neutropenia, leukopenia, anemia, diarrhea, and febrile neutropenia. However, these effects were managed effectively with supportive care. SG currently has an accelerated approval for patients with locally advanced or metastatic urothelial cancer who have received platinum-based chemotherapy and either programmed cell death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. Several studies are evaluating SG in urothelial cancers as single-agent or in combination with other agents.


Assuntos
Anticorpos Monoclonais Humanizados , Camptotecina , Carcinoma de Células de Transição , Imunoconjugados , Neoplasias da Bexiga Urinária , Anticorpos Monoclonais Humanizados/efeitos adversos , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Carcinoma de Células de Transição/tratamento farmacológico , Ensaios Clínicos Fase II como Assunto , Diarreia/induzido quimicamente , Humanos , Imunoconjugados/efeitos adversos , Irinotecano , Neutropenia/induzido quimicamente , Neoplasias da Bexiga Urinária/tratamento farmacológico
14.
Cochrane Database Syst Rev ; 3: CD008524, 2022 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-35294044

RESUMO

BACKGROUND: Vitamin A deficiency (VAD) is a major public health problem in low- and middle-income countries, affecting 190 million children under five years of age and leading to many adverse health consequences, including death. Based on prior evidence and a previous version of this review, the World Health Organization has continued to recommend vitamin A supplementation (VAS) for children aged 6 to 59 months. The last version of this review was published in 2017, and this is an updated version of that review. OBJECTIVES: To assess the effects of vitamin A supplementation (VAS) for preventing morbidity and mortality in children aged six months to five years. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, six other databases, and two trials registers up to March 2021. We also checked reference lists and contacted relevant organisations and researchers to identify additional studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and cluster-RCTs evaluating the effect of synthetic VAS in children aged six months to five years living in the community. We excluded studies involving children in hospital and children with disease or infection. We also excluded studies evaluating the effects of food fortification, consumption of vitamin A rich foods, or beta-carotene supplementation. DATA COLLECTION AND ANALYSIS: For this update, two review authors independently assessed studies for inclusion resolving discrepancies by discussion. We performed meta-analyses for outcomes, including all-cause and cause-specific mortality, disease, vision, and side effects. We used the GRADE approach to assess the quality of the evidence. MAIN RESULTS: The updated search identified no new RCTs. We identified 47 studies, involving approximately 1,223,856 children. Studies were set in 19 countries: 30 (63%) in Asia, 16 of these in India; 8 (17%) in Africa; 7 (15%) in Latin America, and 2 (4%) in Australia. About one-third of the studies were in urban/periurban settings, and half were in rural settings; the remaining studies did not clearly report settings. Most studies included equal numbers of girls and boys and lasted about one year. The mean age of the children was about 33 months. The included studies were at variable overall risk of bias; however, evidence for the primary outcome was at low risk of bias. A meta-analysis for all-cause mortality included 19 trials (1,202,382 children). At longest follow-up, there was a 12% observed reduction in the risk of all-cause mortality for VAS compared with control using a fixed-effect model (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.83 to 0.93; high-certainty evidence). Nine trials reported mortality due to diarrhoea and showed a 12% overall reduction for VAS (RR 0.88, 95% CI 0.79 to 0.98; 1,098,538 children; high-certainty evidence). There was no evidence of a difference for VAS on mortality due to measles (RR 0.88, 95% CI 0.69 to 1.11; 6 studies, 1,088,261 children; low-certainty evidence), respiratory disease (RR 0.98, 95% CI 0.86 to 1.12; 9 studies, 1,098,538 children; low-certainty evidence), and meningitis. VAS reduced the incidence of diarrhoea (RR 0.85, 95% CI 0.82 to 0.87; 15 studies, 77,946 children; low-certainty evidence), measles (RR 0.50, 95% CI 0.37 to 0.67; 6 studies, 19,566 children; moderate-certainty evidence), Bitot's spots (RR 0.42, 95% CI 0.33 to 0.53; 5 studies, 1,063,278 children; moderate-certainty evidence), night blindness (RR 0.32, 95% CI 0.21 to 0.50; 2 studies, 22,972 children; moderate-certainty evidence), and VAD (RR 0.71, 95% CI 0.65 to 0.78; 4 studies, 2262 children, moderate-certainty evidence). However, there was no evidence of a difference on incidence of respiratory disease (RR 0.99, 95% CI 0.92 to 1.06; 11 studies, 27,540 children; low-certainty evidence) or hospitalisations due to diarrhoea or pneumonia. There was an increased risk of vomiting within the first 48 hours of VAS (RR 1.97, 95% CI 1.44 to 2.69; 4 studies, 10,541 children; moderate-certainty evidence). AUTHORS' CONCLUSIONS: This update identified no new eligible studies and the conclusions remain the same. VAS is associated with a clinically meaningful reduction in morbidity and mortality in children. Further placebo-controlled trials of VAS in children between six months and five years of age would not change the conclusions of this review, although studies that compare different doses and delivery mechanisms are needed. In populations with documented VAD, it would be unethical to conduct placebo-controlled trials.


Assuntos
Sarampo , Transtornos Respiratórios , Deficiência de Vitamina A , Criança , Pré-Escolar , Diarreia/induzido quimicamente , Suplementos Nutricionais , Feminino , Humanos , Masculino , Sarampo/induzido quimicamente , Sarampo/complicações , Morbidade , Vitamina A/uso terapêutico , Deficiência de Vitamina A/epidemiologia , Deficiência de Vitamina A/prevenção & controle
15.
Am J Cardiovasc Drugs ; 22(3): 299-323, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35316484

RESUMO

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of anti-hyperglycemic drugs that has been steadily increasing in popularity due to its cardiovascular and renal benefits. Dual SGLT1/SGLT2 (SGLT1/2) inhibitors have potentially augmented anti-hyperglycemic action due to additional SGLT1 inhibition. This network meta-analysis aimed to compare the treatment effect across various outcomes between pure SGLT2 inhibitors and combined SGLT1/2 inhibitors in patients with diabetes. METHODOLOGY: Four electronic databases (PubMed, Embase, Cochrane, and Scopus) were searched for randomized controlled trials published from inception to 15th January 2022. Frequentist network meta-analysis was conducted to summarize the treatment effects reported in individual trials, stratified by type 1 (T1DM) and type 2 diabetes mellitus (T2DM). This meta-analysis was registered on PROSPERO (CRD42020222031). RESULTS: Our meta-analysis included 111 articles, comprising a combined cohort of 103,922 patients. SGLT2 inhibitors (dapagliflozin, empagliflozin, canagliflozin, ipragliflozin, ertugliflozin, and luseogliflozin) and SGLT1/2 inhibitors (licogliflozin and sotagliflozin) were compared. Frequentist network meta-analysis demonstrated that in T2DM patients, SGLT1/2 inhibitors led to a decreased hazard rate of myocardial infarction (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.56-0.98) and stroke (HR 0.65, 95% CI 0.47-0.92) compared with SGLT2 inhibitors. SGLT2 inhibitors achieved a greater hemoglobin A1c (HbA1c) reduction than SGLT1/2 inhibitors (0.16%, 95% CI 0.06-0.26). In patients with T2DM, the risk of diarrhea (risk ratio [RR] 1.42, 95% CI 1.07-1.88) and severe hypoglycemia (RR 5.89, 95% CI 1.41-24.57) were found to be higher with SGLT1/2 inhibitor use compared with SGLT2 inhibitor use. No differences were observed for cardiovascular, metabolic, and safety outcomes between SGLT1/2 inhibitors and SGLT2 inhibitors in patients with T1DM. CONCLUSIONS: In patients with T2DM, compared with pure SGLT2 inhibitors, combined SGLT1/2 inhibitors demonstrated a lower risk of myocardial infarction and of stroke, but were associated with a higher risk of diarrhea and severe hypoglycemia.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Hipoglicemia , Infarto do Miocárdio , Inibidores do Transportador 2 de Sódio-Glicose , Acidente Vascular Cerebral , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diarreia/induzido quimicamente , Glucose , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/complicações , Hipoglicemia/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Infarto do Miocárdio/tratamento farmacológico , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Sódio/uso terapêutico , Transportador 2 de Glucose-Sódio/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Acidente Vascular Cerebral/tratamento farmacológico
16.
Glycoconj J ; 39(1): 131-141, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35286528

RESUMO

Antibiotic-associated diarrhea (AAD) is a common side-effect of antibiotic treatment resulting from an imbalance in the colonic bacteria. The hypothesis of this study is to ask whether polysaccharide from the rhizome of Dioscorea opposita which is recorded as conventional herbs and food for diarrhea treatment in Southeast Asia, may be an active compound against diarrhea induced by antibiotics. To address, firstly, a homogenous polysaccharide, DOP0.2-S-3 was characterized as a homogalacturonan containing linear repeating units of → 4)-α-D-GalAp(1 → 4)-α-D-GalAp(1 → with the average molecular weight of 14 kDa. DOP0.2-S-3 significantly reduced the water content and defecation times caused by AAD in mice, while it also remarkably attenuated the cytokines of IL-1ß and IL-6 expression in mice colon tissues. DOP0.2-S-3 decreased potential pathogen and increased Bacteroidetes in the mice gut. These results suggested DOP0.2-S-3 might be a new leading compound for the functional foods or drug candidate development against AAD partially through regulating gut flora.


Assuntos
Dioscorea , Animais , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Interleucina-1 , Interleucina-6/genética , Camundongos , Pectinas
17.
Expert Opin Emerg Drugs ; 27(1): 55-73, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35266839

RESUMO

INTRODUCTION: Irritable bowel syndrome (IBS) is a symptom-based disorder of chronic abdominal pain and altered bowel habits. The pathogenesis of IBS is multifactorial, leading to the potential for the development of diverse treatment strategies. This mechanistic heterogeneity suggests that available therapies will only prove effective in a subset of IBS sufferers. Current US Food and Drug Administration (FDA) approved therapies for IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C) are reviewed. Limited symptom responses and side effect experiences lead to considerable patient dissatisfaction with currently available IBS treatments. Only a small percentage of IBS patients are on prescription therapies underscoring the potential market and need for additional therapeutic options. AREAS COVERED: Expanding on currently available therapies, the serotonergic and endogenous opioid receptor systems continue to be a focus of future IBS treatment development. Additional novel emerging therapies include the endogenous cannabinoid system, bile acid secretion and sequestration, and exploit our enhanced understanding of visceral sensory signaling and intestinal secretomotor function. EXPERT OPINION: While challenges remain for the future development of IBS therapies, the diverse etiologies underlying the disorder present an opportunity for novel therapies. Hence, great potential is anticipated for future IBS treatment options.


Assuntos
Síndrome do Intestino Irritável , Constipação Intestinal/tratamento farmacológico , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Humanos , Síndrome do Intestino Irritável/induzido quimicamente , Síndrome do Intestino Irritável/tratamento farmacológico
18.
BMC Cancer ; 22(1): 269, 2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35287613

RESUMO

BACKGROUND: The de-escalation treatment in patients with low-risk HER2-positive early breast cancer (eBC) is an attractive strategy to avoid unnecessary treatment and improve the quality of life of patients. Pyrotinib, a novel irreversible pan-HER2 tyrosine kinase inhibitor (TKI), has shown efficacy in patients with advanced HER2-positive breast cancer. Meanwhile, nanoparticle albumin-bound (nab)-paclitaxel reveals survival benefit over solvent-based paclitaxel and eliminates the toxicities associated with the solvent. However, the efficacy and safety of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for low-risk HER2 + eBC patients have not been evaluated. METHODS: This is a multicenter, open-label, single-arm phase II study. A sample size of 261 patients with tumor ≤ 3 cm, lymph node-negative (N0) or micrometastatic (N1mi), HER2 + breast cancer will be recruited. Eligible patients will receive nab-paclitaxel 260 mg/m2 once every 3 weeks for 12 weeks and pyrotinib 400 mg once daily for one year. The primary endpoint is invasive disease-free survival. A sub-study will be conducted to investigate different prophylactic strategies for diarrhea, which is the most common adverse event of pan-HER TKIs. One hundred and twenty patients from the main study will be randomly (1:1) allocated to receive loperamide either during the first cycle (4 mg tid on days 1-7, then 4 mg bid on days 8-21) or the first 2 cycles (4 mg tid on days 1-7, then 4 mg bid on days 8-42). The primary endpoint of the sub-study is the incidence of grade ≥ 3 diarrhea. DISCUSSION: This is the first prospective study of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for patients with low-risk HER2-positive eBC. It would probably provide robust evidence for de-escalating strategy of HER2-positive eBC and appropriate management for pyrotinib-related diarrhea. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04659499 . Registered on December 9, 2020.


Assuntos
Acrilamidas/administração & dosagem , Albuminas/administração & dosagem , Aminoquinolinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Paclitaxel/administração & dosagem , Acrilamidas/efeitos adversos , Albuminas/efeitos adversos , Aminoquinolinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/metabolismo , Quimioterapia Adjuvante/efeitos adversos , Ensaios Clínicos Fase II como Assunto , Diarreia/induzido quimicamente , Diarreia/epidemiologia , Feminino , Humanos , Incidência , Estadiamento de Neoplasias , Paclitaxel/efeitos adversos , Estudos Prospectivos , Qualidade de Vida , Receptor ErbB-2/metabolismo , Resultado do Tratamento
19.
Zhongguo Zhong Yao Za Zhi ; 47(5): 1316-1326, 2022 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-35343160

RESUMO

This study was aimed to explore the effect of Zingiberis Rhizoma extract on rats with antibiotic-associated diarrhea(AAD), and reveal the modulation of gut microbiota during alleviation of AAD. AAD rat model was successfully established by exposing rats to appropriate antibiotic mixed solution. Peficon(70 mg·kg~(-1)·d~(-1)) was used as positive control, then rats were treated with 200 mg·kg~(-1)·d~(-1) and 400 mg·kg~(-1)·d~(-1) of Zingiberis Rhizoma extract for low and high dosage groups of Zingiberis Rhizoma extract, respectively. The weight changes of the rats were observed, and the degree of diarrhea were evaluated by fecal score, 120 min fecal weight and fecal water content. Colon tissues for histopathological examination were stained with hematoxylin and eosin(HE), and 16 S rRNA sequencing analysis of gut microbiota was performed. The results showed that compared with the model group, the degree of diarrhea, indicated by fecal water content, fecal score, and 120 min fecal weight of positive control group, Zingiberis Rhizoma low-dose group and Zingiberis Rhizoma high-dose group were significantly ameliorated. And the treatment of Zingiberis Rhizoma could significantly improve the pathological condition of colon tissue in AAD rats, especially the high dose of Zingiberis Rhizoma. In addition, 16 S rRNA sequencing analysis of gut microbiota showed that the diversity and abundance of gut microbiota were significantly improved and the reco-very of gut microbiota was accelerated after given high-dose of Zingiberis Rhizoma, while no significant changes of alterations were observed after given Pefikon. Of note, compared with the pefikon group, the abundance and diversity of gut microbiota in Zingi-beris Rhizoma high-dose group were significantly elevated. At the phylum level, the abundance of Firmicutes in AAD rats increased and the abundance of Proteobacteria was decreased after the Zingiberis Rhizoma intervention. At the genus level, the abundance of Bacillus spp., Lachnoclostridium and Escherichia coli-Shigella were decreased, and the abundance of Lactobacillus spp., Trichophyton spp., and Trichophyton spp., etc., were increased. While compared with the AAD model group, there was no significant difference of gut microbiota after given Peficon. The results showed that Zingiberis Rhizoma exerted beneficial health effects against AAD, and positively affected the microbial environment in the gut of rats with AAD.


Assuntos
Microbioma Gastrointestinal , Animais , Antibacterianos/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Gengibre , Extratos Vegetais , Ratos , Rizoma
20.
Medicina (Kaunas) ; 58(3)2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35334570

RESUMO

Background and Objectives: Diarrhea induced by chemotherapy may represent a life-threatening adverse effect in cancer patients receiving chemotherapy. FOLFOX, an effective treatment for colon cancer, has been associated with diarrhea with high severity, particularly with higher doses. Management of diarrhea is crucial to increase the survival of cancer patients and to improve the quality of life. Glutamine is an abundant protein peptide found in blood and has a crucial role in boosting immunity, increasing protein anabolism, and decreasing the inflammatory effects of chemotherapy on the mucosal membranes, including diarrhea. This study aimed to provide evidence that parenteral L-alanyl L-glutamine dipeptide may have a positive influence on the incidence of diarrhea, treatment response, and the overall survival in colon cancer patients treated with modified FOLFOX-6 (mFOLFOX-6). Materials and Methods: Forty-four stage II and III colon cancer patients were included in this study where they were treated with the standard colon cancer chemotherapy mFOLFOX-6 and were randomly allocated into glutamine group and placebo group, each of 22 patients. Results: L-alanyl L-glutamine dipeptide was found to be significantly effective in decreasing the frequency and severity of diarrhea when compared to the placebo group, particularly after four and six cycles of mFOLFOX-6. There was no significant difference between the studied groups regarding to the overall survival. Conclusion: L-alanyl L-glutamine dipeptide can be considered as an add-on with chemotherapy to improve the quality of life and the overall survival of colon cancer patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo , Glutamina , Neoplasias do Colo/tratamento farmacológico , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Dipeptídeos/farmacologia , Dipeptídeos/uso terapêutico , Fluoruracila/uso terapêutico , Glutamina/farmacologia , Humanos , Incidência , Leucovorina/uso terapêutico , Compostos Organoplatínicos/uso terapêutico , Qualidade de Vida
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