Detection of TRPM6 and TRPM7 Proteins in Normal and Diseased Cardiac Atrial Tissue and Isolated Cardiomyocytes.

Magnesium-sensitive transient receptor potential melastatin (TRPM) ion channels, TRPM6 and TRPM7, are present in several organs, but their roles in the heart remain unclear. Therefore, here, we studied the expression patterns of TRPM6 and TRPM7 in normal and diseased myocardium. Cardiac atrial tissue and cardiomyocytes were obtained from healthy pigs and undiseased human hearts as well as from hearts of patients with ischemic heart disease (IHD) or atrial fibrillation (AF).

Emerging role of transient receptor potential (TRP) ion channels in cardiac fibroblast pathophysiology.

Cardiac fibroblasts make up a major proportion of non-excitable cells in the heart and contribute to the cardiac structural integrity and maintenance of the extracellular matrix. During myocardial injury, fibroblasts can be activated to trans-differentiate into myofibroblasts, which secrete extracellular matrix components as part of healing, but may also induce cardiac fibrosis and pathological cardiac structural and electrical remodeling. The mechanisms regulating such cellular processes still require clarification, but the identification of transient receptor potential (TRP) channels in cardiac fibroblasts could provide further insights into the fibroblast-related pathophysiology.

Assessment of proarrhythmogenic risk for chloroquine and hydroxychloroquine using the CiPA concept.

Chloroquine and hydroxychloroquine have been proposed recently as therapy for SARS-CoV-2-infected patients, but during 3 months of extensive use concerns were raised related to their clinical effectiveness and arrhythmogenic risk. Therefore, we estimated for these compounds several proarrhythmogenic risk predictors according to the Comprehensive in vitro Proarrhythmia Assay (CiPA) paradigm. Experiments were performed with either CytoPatch™2 automated or manual patch-clamp setups on HEK293T cells stably or transiently transfected with hERG1, hNav1.

Modulation of the Cardiac Myocyte Action Potential by the Magnesium-Sensitive TRPM6 and TRPM7-like Current.

The cardiac Mg-sensitive, TRPM6, and TRPM7-like channels remain undefined, especially with the uncertainty regarding TRPM6 expression in cardiomyocytes. Additionally, their contribution to the cardiac action potential (AP) profile is unclear. Immunofluorescence assays showed the expression of the TRPM6 and TRPM7 proteins in isolated pig atrial and ventricular cardiomyocytes, of which the expression was modulated by incubation in extracellular divalent cation-free conditions.

Evidence for the expression of TRPM6 and TRPM7 in cardiomyocytes from all four chamber walls of the human heart.

The expression of the channels-enzymes TRPM6 and TRPM7 in the human heart remains poorly defined, and TRPM6 is generally considered not to be expressed in cardiomyocytes. We examined their expression at protein and mRNA levels using right atrial samples resected from patients (n = 72) with or without ischemic heart disease (IHD) and samples from all chamber walls of explanted human hearts (n = 9). TRPM6 and TRPM7 proteins were detected using immunofluorescence on isolated cardiomyocytes, ELISA on tissue homogenates, and immunostaining of cardiac tissue, whereas their mRNAs were detected by RT-qPCR.

Atypical respiratory distress in eastern Democratic Republic of the Congo prior to the COVID-19 pandemic. A case report.

Background: Predictions have been made that Africa would be the most vulnerable continent to the novel Coronavirus disease 2019 (COVID-19). Interestingly, the spread of the disease in Africa seems to have been delayed and initially slower than in many parts of the world. Here we report on two cases of respiratory distress in our region before the official declaration of the disease in December 2019, cases which in the present times would be suspect of COVID-19.

Cardiac effects and toxicity of chloroquine: a short update.

There is currently increased interest in the use of the antimalarial drugs chloroquine and hydroxychloroquine for the treatment of other diseases, including cancer and viral infections such as coronavirus disease 2019 (COVID-19). However, the risk of cardiotoxic effects tends to limit their use. In this review, the effects of these drugs on the electrical and mechanical activities of the heart as well as on remodelling of cardiac tissue are presented and the underlying molecular and cellular mechanisms are discussed.

[Assessment of virological quality of transfused blood in the town of Bukavu, South Kivu, Democratic Republic of Congo].

Introduction: In Bukavu, transfused blood is selected using rapid diagnostic tests (RDTs). These tests are easily performed without specialized equipments. This study aims to evaluate the virological quality of transfused blood assessed using rapid diagnostic tests.

[Antibiotic resistance of Salmonella spp strains isolated from blood cultures in Bukavu, Democratic Republic of the Congo].

Introduction: Typhoid fever is a major public health problem in developing countries because of the obsolescence of health infrastructure and of an almost non-existent water distribution network. In the Democratic Republic of the Congo, in general, and in Bukavu, in particular, blood culture is inaccessible to the majority of patients. This study aimed to assess the sensitivity of Salmonella spp to antibiotics commonly used for the tratment of typhoid fever in Bukavu.

Performance of SD Bioline Malaria Ag Pf/Pan rapid test in the diagnosis of malaria in South-Kivu, DR Congo.

Introduction: Use of malaria rapid diagnostic tests (RDTs) has improved the management of this disease. We evaluated the validity of the SD-Bioline Malaria-Ag-Pf/Pan™ (Batch 60952) RDT supplied by the Malaria Control Program of the DRCongo.

Methods: cChildren (n = 460) aged below 5 years seen in curative care (CC) for suspected malaria and in pre-school consultation (PSC) in two rural centers underwent clinical evaluation and capillary blood collection for microscopic reading of thick smear (TS) and thin film (BF), and for RDT.

High Prevalence of Anemia but Low Level of Iron Deficiency in Preschool Children during a Low Transmission Period of Malaria in Rural Kivu, Democratic Republic of the Congo.

Anemia is a worldwide public health concern especially in preschool children in developing countries and iron deficiency (ID) is generally assumed to cause at least 50% of the cases. However, data on this contribution are scarce. To close this gap, we determined in 2013 the contribution of ID in the etiology of anemia and measured others factors associated to noniron deficiency anemia (NIDA) in 900 preschool children randomly selected during a two-stage cluster nutritional survey in the Miti-Murhesa health zone, in eastern Democratic Republic of the Congo.

Modulation of Human Cardiac TRPM7 Current by Extracellular Acidic pH Depends upon Extracellular Concentrations of Divalent Cations.

TRPM7 channels participate in a variety of physiological/pathological processes. TRPM7 currents are modulated by protons but opposing effects of external pH (pHo) (potentiation vs inhibition) have been reported. TRPM7 has been less studied in human cardiomyocytes than in heart-derived non-cardiomyocyte cells.

Vascular Endothelium-Dependent and Independent Actions of Oleanolic Acid and Its Synthetic Oleanane Derivatives as Possible Mechanisms for Hypotensive Effects.

Purpose: Plant-derived oleanolic acid (OA) and its related synthetic derivatives (Br-OA and Me-OA) possess antihypertensive effects in experimental animals. The present study investigated possible underlying mechanisms in rat isolated single ventricular myocytes and in vascular smooth muscles superfused at 37°C.

Methods: Cell shortening was assessed at 1 Hz using a video-based edge-detection system and the L-type Ca2+ current (ICaL) was measured using the whole-cell patch-clamp technique in single ventricular myocytes.

Response to exercise and mechanical efficiency in non-ischaemic stunning, induced by short-term rapid pacing in dogs: a role for calcium?

Aim: Rapid pacing (RP) is a regularly used model to induce heart failure in dogs. The aim of the study was to evaluate Ca handling, left ventricular (LV) contractile response during Ca administration compared to exercise, as well as oxygen consumption and mechanical efficiency after 48 h of RP.

Methods: Fifty-three mongrel dogs were instrumented to measure LV pressure, LV fractional shortening, regional wall thickening and coronary blood flow.

Changes in Renal Function and Oxidative Status Associated with the Hypotensive Effects of Oleanolic Acid and Related Synthetic Derivatives in Experimental Animals.

Purpose: The triterpene oleanolic acid (OA) is known to possess antihypertensive actions. In the present study we to compared the effects of the triterpene on mean arterial blood pressure (MAP) and kidney function following acute administration in normotensive animals with those of its related oleanane synthetic derivatives (brominated oleanolic acid, Br-OA and oleanolic acid methyl ester, Me-OA). We also used experimental models of hypertension to further explore the effects of sub-chronic oral OA treatment and evaluated influences on oxidative status.

Prevalence of colonization by Streptococcus agalactiae among pregnant women in Bukavu, Democratic Republic of the Congo.

Introduction: Maternal vaginal colonization by Streptococcus agalactiae (GBS) has an important impact on neonatal health but has not been studied in the Democratic Republic of Congo. The aim of this study was to determine its frequency and influencing factors.

Methodology: Vaginal samples (n = 509) for bacteriological analysis were collected from women in Bukavu, eastern DR Congo, during their third trimester of pregnancy, along with information about age, education and socio-economic status, and medical and obstetric-gynecological history.

NO-dependent endothelial dysfunction in type II diabetes is aggravated by dyslipidemia and hypertension, but can be restored by angiotensin-converting enzyme inhibition and weight loss.

Aims: Insulin resistance, dyslipidemia and hypertension are independent mediators of endothelial dysfunction. It is incompletely defined whether dyslipidemia and hypertension in addition to diabetes mellitus type II (DMII), as seen in the metabolic syndrome (MS), worsen diabetes-induced endothelial dysfunction. Furthermore, it is unclear whether treatment influences endothelial dysfunction similarly in MS and DMII.

ACE-inhibition, but not weight reduction restores cardiomyocyte response to β-adrenergic stimulation in the metabolic syndrome.

Background: Diabetic cardiomyopathy is characterized by systolic and early diastolic ventricular dysfunction. In the metabolic syndrome (MS), ventricular stiffness is additionally increased in a later stage. It is unknown whether this is related to intrinsic cardiomyocyte dysfunction, extrinsic factors influencing cardiomyocyte contractility and/or cardiac function, or a combination of both.

The cardiac atrial appendage stem cell: a new and promising candidate for myocardial repair.

Aims: Considerable shortcomings in the treatment of myocardial infarction (MI) still exist and therefore mortality remains high. Cardiac stem cell (CSC) therapy is a promising approach for myocardial repair. However, identification and isolation of candidate CSCs is mainly based on the presence or absence of certain cell surface markers, which suffers from some drawbacks.

Insights into the effects of diclofenac and other non-steroidal anti-inflammatory agents on ion channels.

Objectives: Diclofenac and other non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of inflammation and pain. Most effects of NSAIDs are attributed to the inhibition of cyclooxygenases (COX). However, many NSAIDs may have other effects not related to COX, including the modulation of various ion channels.

Inhibition of the calcium-activated chloride current in cardiac ventricular myocytes by N-(p-amylcinnamoyl)anthranilic acid (ACA).

N-(p-amylcinnamoyl)anthranilic acid (ACA), a phospholipase A(2) (PLA(2)) inhibitor, is structurally-related to non-steroidal anti-inflammatory drugs (NSAIDs) of the fenamate group and may also modulate various ion channels. We used the whole-cell, patch-clamp technique at room temperature to investigate the effects of ACA on the Ca(2+)-activated chloride current (I(Cl(Ca))) and other chloride currents in isolated pig cardiac ventricular myocytes. ACA reversibly inhibited I(Cl(Ca)) in a concentration-dependent manner (IC(50)=4.

Induction of a novel cation current in cardiac ventricular myocytes by flufenamic acid and related drugs.

Background And Purpose: Interest in non-selective cation channels has increased recently following the discovery of transient receptor potential (TRP) proteins, which constitute many of these channels.

Experimental Approach: We used the whole-cell patch-clamp technique on isolated ventricular myocytes to investigate the effect of flufenamic acid (FFA) and related drugs on membrane ion currents.

Key Results: With voltage-dependent and other ion channels inhibited, cells that were exposed to FFA, N-(p-amylcinnamoyl)anthranilic acid (ACA), ONO-RS-082 or niflumic acid (NFA) responded with an increase in currents.