Risk of Cardiac Lesion with Chronic and Acute Use of Loperamide-An Integrative Review.

Loperamide is a synthetic opioid commonly used as an antidiarrheal due to its activation of u-opioid receptors in the myenteric plexus. In therapeutic doses, it inhibits peristalsis and has anti-secretory and anti-motility effects, until metabolized by intestinal and hepatic CYP3A4 and CYP2C8 into inactive metabolites. Furthermore, loperamide also inhibits L-type voltage-gated calcium (Ca2+) channels, increases action potential duration, and can induce arrhythmias and even cardiotoxicity, particularly when taken in extremely high doses. Thus, the aim of this study was to perform an integrative review of the available evidence in the recent literature on the cardiac risks of acute and chronic use of loperamide. In electrocardiogram (ECG) analysis, the most common finding was QTc prolongation in 27 cases, followed by QRS prolongation, first-degree atrioventricular (AV) block, torsades de pointes, ventricular tachycardia, and right bundle branch block. As for the symptoms encountered, syncope, weakness, palpitations, lightheadedness, shortness of breath, nausea, vomiting, bradycardia, and cardiac arrest were the most common. Loperamide can inhibit hERG voltage-gated potassium (K+) channels (Kv11.1), leading to the prolongation of repolarization, QTc interval prolongation, and increased risk of torsades de pointes. In addition, loperamide can inhibit voltage-gated sodium (Na+) channels (Nav1.5), impairing electrical cardiac conduction and potentiating QRS interval widening. Therefore, QTc prolongation, torsades de pointes, and other ECG alterations are of particular concern regarding loperamide toxicity, particularly when overdosed.

The effect of pilates on metabolic control and oxidative stress of diabetics type 2 - A randomized controlled clinical trial.

INTRODUCTION: The Pilates method is an approach to body and mind exercises that has as its foundation the gain of stability, strength and flexibility, and the work of muscular control, posture and breathing, which can generate repercussions on oxidative stress and ROS production, it is expected that Pilates can satisfactorily influence glycemic and oxidative stress reduction in elderly diabetes. AIM: To analyze the effect of a Pilates protocol on variables indicative of metabolic control and oxidative stress in patients with Type 2 Diabetes Mellitus. METHOD: Randomized clinical trial in type 2 diabetics enrolled in Hiperdia Parnaíba. A Pilates protocol was performed for 8 weeks, with 2 weekly consultations. The tested variables were: blood glucose, glycated hemoglobin, lipid profile, C-reactive protein and malondialdehyde. ANOVA tests, correlation of Wilcoxon, Friedman and Spearman, were used, with a significance level of 5%. RESULTS: 44 diabetics participated in the study (intervention group: 22; control: 22), with a mean age of 61.23 ± 8.49years, the majority being female (77.3%), married (59.1%), literate (31.8%), with an average BMI of 26.96 ± 4.35 kg/m2. When analyzing the effects of the protocol, there was a significant reduction in glycated hemoglobin (p = 0.002) and oxidative stress (p = 0.004) in the intervention group, however, there were no differences in fasting glucose (p = 0.055) and in the profile lipid, expressed by the total cholesterol (p = 0.654), HDL (p = 0.591), LDL (p = 0.564) and triglycerides (0.192). There was a moderate positive correlation between oxidative stress and glycated hemoglobin (r = 0.44, p = 0.000). CONCLUSION: The exercise protocol based on the Pilates method produced a reduction in glycated hemoglobin and oxidative stress.

Antifungal and anti-inflammatory potential of eschweilenol C-rich fraction derived from Terminalia fagifolia Mart.

ETHNOPHARMACOLOGICAL RELEVANCE: Folk knowledge transmitted between generations allows traditional populations to maintain the use of medicinal plants for the treatment of several diseases. In this context, the species Terminalia fagifolia Mart., native to Brazil, is used for the treatment of chronic and infectious diseases. Plants rich in secondary metabolites, such as this species and their derivatives, may represent therapeutic alternatives for the treatment of diseases that reduce the quality of life of people. AIM OF THE STUDY: The aim of this study was to evaluate the antifungal and anti-inflammatory potential of aqueous fraction from ethanolic extract of T. fagifolia, with in silico study of the major compound of the fraction. MATERIAL AND METHODS: The phytochemical study of the aqueous fraction was performed by HPLC, LC/MS and NMR. The antifungal activity was evaluated against yeasts, by determination of the minimum inhibitory concentration and minimum fungicidal concentration. The effect on Candida albicans was analyzed by AFM. The antibiofilm potential against biofilms of C. albicans was also tested. The anti-inflammatory potential of the aqueous fraction was evaluated in vivo by the carrageenan-induced paw edema and peritonitis. A microglial model of LPS-induced neuroinflammation was also studied. Further insights on the activation mechanism were studied using quantum chemistry computer simulations. Toxicity was evaluated in the Galleria mellonella and human erythrocytes models. RESULTS: Eschweilenol C was identified as the major constituent of the aqueous fraction of the ethanolic extract of T. fagifolia. The aqueous fraction was active against all Candida strains used (sensitive and resistant to Fluconazole) with MICs ranging from 1000 to 0.4 µg/mL. By AFM it was possible to observe morphological alterations in treated Candida cells. The fraction significantly (p < 0.05) inhibited paw edema and decreased levels of malondialdehyde induced by carrageenan. In a microglial cell model, aqueous fraction demonstrated the ability to inhibit NF-κB after induction with lipopolysaccharide. The theoretical studies showed structural similarity between eschweilenol C and indomethacin and an excellent antioxidant potential. The aqueous fraction did not present toxicity in the studied models. CONCLUSION: The results indicate that the aqueous fraction of T. fagifolia has potential for biomedical applications with low toxicity. This finding can be attributed to the predominance of eschweilenol C in the aqueous fraction.

Preventive effect of bergenin against the development of TNBS-induced acute colitis in rats is associated with inflammatory mediators inhibition and NLRP3/ASC inflammasome signaling pathways.

Ulcerative colitis is an idiopathic inflammatory bowel disease characterized by intestinal inflammation; blocking this inflammatory process may be the key to the development of new naturally occurring anti-inflammatory drugs, with greater efficiency and lower side effects. The objective of this study is to explore the effects of bergenin (BG) in TNBS (2,4,6-trinitrobenzenesulfonic acid)-induced acute colitis model in rats in order to assist in the studies for the development of novel natural product therapies for inflammatory bowel disease. 48 Wistar rats were randomized into six groups: (i) Control and (ii) TNBS control; (iii) 5-ASA 100 mg/kg/day (iv) BG 12 mg/kg/day (v) BG 25 mg/kg/day and (vi) BG 50 mg/kg/day. Colitis was induced by instillation of TNBS. Colitis was evaluated by an independent observer who was blinded to the treatment. Our results revealed that bergenin decreased the macroscopic and microscopic damage signs of colitis, and reduced the degree of neutrophilic infiltration in the colon tissue; also, it was capable to down-regulate COX-2, iNOS, IkB-α, and pSTAT3 protein expression. Similarly, using a protocol for indirect ELISA quantification of cytokines, bergenin treatment reduced IL-1ß, IFN-γ and IL-10 levels, and inhibited both canonical (IL-1) and non-canonical (IL-11) NLRP3/ASC inflammasome signaling pathways in TNBS-induced acute colitis. Conclusion: Our study has provided evidence that administration of bergenin reduced the damage caused by TNBS in an experimental model of acute colitis in rats, reduced levels of pro-inflammatory proteins and cytokines probably by modulation of pSTAT3 and NF-κB signaling and blocking canonical and non-canonical NLRP3/ASC inflammasome pathways.