Lithium Treatment Induces Cardiac Dysfunction in Mice.

Lithium (Li) salts are commonly used as medications for bipolar disorders. In addition to its therapeutic value, Li is also being increasingly used as a battery component in modern electronic devices. Concerns about its toxicity and negative impact on the heart have recently been raised. We investigated the effects of long-term Li treatment on the heart, liver, and kidney in mice. Sixteen C57BL/6J mice were randomly assigned to receive oral administration of Li carbonate (n = 8) or act as a control group (n = 8) for 12 weeks. We evaluated the cardiac electrical activity, morphology and function, and pathways contributing to remodelling. We assessed the multi-organ toxicity using histopathology techniques in the heart, liver, and kidney. Our findings suggest that mice receiving Li had impaired systolic function and ventricular repolarisation and were more susceptible to arrhythmias under adrenergic stimulation. The Li treatment caused an increase in the cardiomyocytes' size, the modulation of the extracellular signal-regulated kinase (ERK) pathway, along with some minor tissue damage. Our findings revealed a cardiotoxic effect of Li at therapeutic dosage, along with some histopathological alterations in the liver and kidney. In addition, our study suggests that our model could be used to test potential treatments for Li-induced cardiotoxicity.

Myo-inositol and d-chiro-inositol oral supplementation ameliorate cardiac dysfunction and remodeling in a mouse model of diet-induced obesity.

Obesity is an independent risk factor to develop cardiac functional and structural impairments. Here, we investigated the effects of supplementation of inositols on the electrical, structural, and functional cardiac alterations in the mouse model of high fat diet (HFD) induced obesity. Three groups of C57BL6 mice (n = 16 each) were studied: j) HFD feeding; jj) HFD feeding + inositols from week 9 to 13; jjj) standard diet feeding. Study observation period was 13 weeks. Inositols were administered as mixture of myo-inositol and d-chiro-inositol in the drinking water. Effects of inositols were evaluated based on electrical, structural, and functional cardiac features, autonomic sympatho-vagal balance and arrhythmogenic susceptibility to adrenergic challenge. Heart samples were collected for histological evaluations and transcriptional analyses of genes involved in defining the shape and propagation of the action potential, fatty acid metabolism and oxidative stress. Inositol supplementation significantly restored control values of heart rate and QTc interval on ECG and of sympatho-vagal balance. Moreover, it blunted the increase in left ventricular mass and cardiomyocyte hypertrophy, reversed diastolic dysfunction, reduced the susceptibility to arrhythmic events and restored the expression level of cardiac genes altered by HFD. The present study shows, for the first time, how a short period of supplementation with inositols is able to ameliorate the HFD-induced electrical, structural and functional heart alterations including ventricular remodeling. Results provide a new insight into the cardioprotective effect of inositols, which could pave the way for a novel therapeutic approach to the treatment of HFD obesity-induced heart dysfunction.

Oral supplementation of inositols effectively recovered lithium-induced cardiac dysfunctions in mice.

This study investigates the effects of inositol (INO) supplementation on cardiac changes caused by Li in mice. The study involved 4 groups of C57BL6 mice (n=10 each): (i) mice orally administered with Li2CO3 for 8 weeks, then 4 additional weeks without (Li_group) or (ii) with INO supplementation (Li_INOdelayed_group) (total of 12 weeks); (iii) mice given Li2CO3 and INO supplementation concurrently for 12 weeks (Li+INO_group); (iv) one group left untreated (C-group). The INO was administered as a mixture of myo-inositol and d-chiro-inositol (80:1) in drinking water. The mice were characterised for heart morphology, function, electrical activity, arrhythmogenic susceptibility, and multiorgan histopathology (heart, liver and kidney). Cardiomyocyte size, protein expression of key signalling pathways related to hypertrophy, and transcription levels of ion channel subunits and hypertrophy markers were evaluated in the ventricle tissue. The study found that INO supplementation reduced the Li-induced cardiac adverse effects, including systolic impairment and increased susceptibility to arrhythmias. The positive effect on arrhythmias might be attributed to the restored expression levels of the potassium channel subunit Kv 1.5. Additionally, INO improved cardiomyocyte hypertrophy, possibly by inhibiting the Li-induced activation of the ERK1/2 signalling pathway and by restoring the normal expression level of BNP, and alleviated injury in the liver and kidney. The effect was preventive if INO supplementation was taken concurrently with Li and therapeutic if INO was administered after Li-induced cardiac impairments were established. These results provide new insights into the cardioprotective effect of INO and suggest a potential treatment approach for Li-induced cardiac disease.

Does smoking increase the incidence of postoperative complications in simple exodontia?

OBJECTIVE: To investigate whether smoking has adverse effects in simple exodontia. METHODS: A single-centre, prospective study of postoperative inflammatory complications in simple exodontia was performed. All procedures were conducted under similar and sterile conditions. Postoperative complications (PCs) in exodontia were classified as alveolar osteitis (AO) or alveolar infection (AI) and their incidences then added. RESULTS: A logistic regression model for PCs revealed tooth sectioning [odds ratio (OR) = 4.3, 95% confidence interval (CI) 1.0-18.8; P = 0.050], smoking (OR = 4.5, 95% CI 1.0-18.9; P = 0.03) and amount of smoking (> 20 cigarettes/day: OR = 12.3, 95% CI 1.0-149.8; P = 0.04) to be associated with the occurrence of PCs. CONCLUSIONS: Tooth sectioning, smoking and degree of smoking are all associated with the development of PCs such as AO and AI after simple exodontia. Dentists must be alert to these factors when performing simple exodontia in smokers in view of the increased risk for PCs.

Chorioallantoic membrane tumor models highlight the effects of cisplatin compounds in oral carcinoma treatment.

The European Society for Medical Oncology (ESMO) suggests the use of chemotherapy as neoadjuvant, adjuvant, and concomitant to surgery and radiotherapy for the treatment of oral carcinoma by depending on the cancer stage. The usual drug of choice belongs to the platinum compounds. In this context, the evaluation of the cancer behavior associated with the administration of standard or emerging cisplatin compounds supports the establishment of optimal cancer management. Here, we have assessed and compared the performance of cisplatin alone and contained in biodegradable nanocapsules on standardized chorioallantoic membrane (CAM) tumor models. The vascularized environment and optimized grafting procedure allowed the establishment of solid tumors. The treatments showed antitumor and anti-angiogenic activities together with deregulation of pivotal genes responsible of treatment resistance and tumor aggressiveness. This study further supports the significance of CAM tumor models in oncological research for the comprehension of the molecular mechanisms involved in tumor treatment response.

A Standard Protocol for the Production and Bioevaluation of Ethical In Vivo Models of HPV-Negative Head and Neck Squamous Cell Carcinoma.

Preclinical cancer research increasingly demands sophisticated models for the development and translation of efficient and safe cancer treatments to clinical practice. In this regard, tumor-grafted chorioallantoic membrane (CAM) models are biological platforms that account for the dynamic roles of the tumor microenvironment and cancer physiopathology, allowing straightforward investigations in agreement to the 3Rs concept (the concept of reduction, refinement, and replacement of animal models). CAM models are the next advanced model for tumor biological explorations as well as for reliable assessment regarding initial efficacy, toxicity, and systemic biokinetics of conventional and emerging neoplasm treatment modalities. Here we report a standardized and optimized protocol for the production and biocharacterization of human papillomavirus (HPV)-negative head and neck chick chorioallantoic membrane models from a commercial cell line (SCC-25). Oral malignancies continue to have severe morbidity with less than 50% long-term survival despite the advancement in the available therapies. Thus, there is a persisting demand for new management approaches to establish more efficient strategies toward their treatment. Remarkably, the inclusion of CAM models in the preclinical research workflow is crucial to ethically foster both the basic and translational oncological research on oral malignancies as well as for the advancement of efficient cancer treatment approaches.