Magnesium-to-Calcium Ratio and Mortality from COVID-19

Obesity, type 2 diabetes, arterial hypertension, decrease in immune response, cytokine storm, endothelial dysfunction, and arrhythmias, which are frequent in COVID-19 patients, are associated with hypomagnesemia. Given that cellular influx and efflux of magnesium and calcium involve the same transporters, we aimed to evaluate the association of serum magnesium-to-calcium ratio with mortality from severe COVID-19. The clinical and laboratory data of 1064 patients, aged 60.3 ± 15.7 years, and hospitalized by COVID-19 from March 2020 to July 2021 were analyzed. The data of 554 (52%) patients discharged per death were compared with the data of 510 (48%) patients discharged per recovery. The ROC curve showed that the best cut-off point of the magnesium-to-calcium ratio for identifying individuals at high risk of mortality from COVID-19 was 0.20. The sensitivity and specificity were 83% and 24%. The adjusted multivariate regression model showed that the odds ratio between the magnesium-to-calcium ratio ≤0.20 and discharge per death from COVID-19 was 6.93 (_95%CI 1.6–29.1) in the whole population, 4.93 (_95%CI 1.4–19.1, p = 0.003) in men, and 3.93 (_95%CI 1.6–9.3) in women. In conclusion, our results show that a magnesium-to-calcium ratio ≤0.20 is strongly associated with mortality in patients with severe COVID-19.     

FCGR3A V(176) polymorphism for systemic lupus erythematosus susceptibility in Mexican population

The objective of this study is to establish whether there is an association between the presence of FCGR3A V(176) polymorphism with SLE or its manifestations. We included 94 patients according to the 1982 ACR criteria as well as 98 controls matched by age and gender. The 11 ACR diagnostic criteria were analyzed on the clinical files. The polymorphism FCGR3A V(176) was determined by direct sequencing. There was not an association between the polymorphism FCGR3A V(176) with SLE or its main manifestations. The allelic frequency for F(176) was: 0.80 and 0.72 in cases and controls, respectively (P?=?0.09, IC95%: 0.42?C1.07); and the genotypic frequency in the group of cases was: 0.65 for homozygotes F(176)/F(176), 0.30 for heterozygotes and 0.05 for the homozygotes V(176)/V(176), while for the control group it was 0.53, 0.39 and 0.08, respectively. The polymorphism FCGR3A V(176) is not associated with SLE or any of its manifestations in patients with SLE from the West of Mexico.     

Melatonin enhances neural stem cell differentiation and engraftment by increasing mitochondrial function

Neural stem cells (NSCs) are regarded as a promising therapeutic approach to protecting and restoring damaged neurons in neurodegenerative diseases (NDs) such as Parkinson's disease and Alzheimer's disease (PD and AD, respectively). However, new research suggests that NSC differentiation is required to make this strategy effective. Several studies have demonstrated that melatonin increases mature neuronal markers, which reflects NSC differentiation into neurons. Nevertheless, the possible involvement of mitochondria in the effects of melatonin during NSC differentiation has not yet been fully established. We therefore tested the impact of melatonin on NSC proliferation and differentiation in an attempt to determine whether these actions depend on modulating mitochondrial activity. We measured proliferation and differentiation markers, mitochondrial structural and functional parameters as well as oxidative stress indicators and also evaluated cell transplant engraftment. This enabled us to show that melatonin (25 μM) induces NSC differentiation into oligodendrocytes and neurons. These effects depend on increased mitochondrial mass/DNA/complexes, mitochondrial respiration, and membrane potential as well as ATP synthesis in NSCs. It is also interesting to note that melatonin prevented oxidative stress caused by high levels of mitochondrial activity. Finally, we found that melatonin enriches NSC engraftment in the ND mouse model following transplantation. We concluded that a combined therapy involving transplantation of NSCs pretreated with pharmacological doses of melatonin could efficiently restore neuronal cell populations in PD and AD mouse models depending on mitochondrial activity promotion.     

Leptin as an open secret in the physiopathology of rheumatic diseases

Clinical Rheumatology -     

Association of G-protein-coupled receptor 154 with asthma and total IgE in a population of the Caribbean coast of Colombia

Background G protein‐coupled receptor 154 was described as an asthma susceptibility gene by positional cloning. It has been subsequently associated with asthma and other inflammatory diseases in several populations with different ethnic origin. Replication of associations adds reliability to these findings. Objective To analyze the association of G protein‐coupled receptor 154 with asthma and total and mite‐specific IgE levels in a population of the Caribbean Coast of Colombia. Methods We genotyped seven single nucleotide proteins (SNPs) in GPR154 in 475 asthmatics, 394 controls and 116 families from Cartagena, Colombia using either SnaPshot or TaqMan. Total and specific IgE against Blomia tropicalis and Dermatophagoides pteronyssinus were determined by ELISA. Hardy–Weinberg equilibrium was assessed and case–control and family‐based analyses were performed to evaluate the association between the SNPs and their haplotypes and asthma and IgE. Association analyses in the case–control dataset were corrected by population stratification using 52 ancestry informative markers. Results Allelic distribution was similar to that described in other populations. Two SNPs were associated with the same direction of the effect in both datasets. Allele A of Hopo546333 was protective for asthma (case–control OR: 0.42; 95% CI: 0.17–0.99, P=0.042; P=0.043; families Z score=?2,236; P=0.025). Similarly, allele C of rs740347 conferred low risk for asthma (OR: 0.44; 95% CI: 0.28–0.70, P=0.00017; P_c=0.00037) and total IgE (OR: 0.29; 95% CI: 0.09–0.88, P=0.015; P_c=0.030) in the case–control study and families (Z score=?3.207, P=0.0013; Z score=?3.182, P=0.0014, respectively). Haplotype CCAGGT was associated with total IgE (OR: 1.76; 95% CI: 1.14–2.71, P=0.006, P_c=0.007) in the case–controls group and CGCGGT with both phenotypes (P=0.044 and P=0.032, respectively) in families. Neither SNPs nor haplotypes were associated with levels of mite‐specific IgE. Conclusions Our findings in a sample of asthmatics from Colombia suggest a relevant role of G protein‐coupled receptor 154 in the pathogenesis of asthma and allergy.     

Prolonged-release pirfenidone prevents obesity-induced cardiac steatosis and fibrosis in a mouse NASH model

Cardiovascular Drugs and Therapy - Obesity is associated with systemic insulin resistance and cardiac hypertrophy with fibrosis. Peroxisome proliferator-activated receptors (PPARs) regulate...     

Long-term fluvastatin reduces the hazardous effect of renal impairment on four-year atherosclerotic outcomes (a LIPS substudy)

Mild renal impairment is an important risk factor for late cardiovascular complications. This substudy of the Lescol Intervention Prevention Study (LIPS) assessed the effect of fluvastatin on outcome of patients who had renal dysfunction and those who did not. Complete data for creatinine clearance calculation (Cockcroft-Gault formula) were available for 1,558 patients (92.9% of the LIPS population). Patients were randomized to fluvastatin or placebo after successful completion of a first percutaneous coronary intervention. Follow-up time was 3 to 4 years. The effect of baseline creatinine clearance on coronary atherosclerotic events (cardiac death, nonfatal myocardial infarction, and coronary reinterventions not related to restenosis) was evaluated. Baseline creatinine clearance (logarithmic transformation) was inversely associated with an incidence of adverse events among patients who received placebo (hazard ratio 0.99, 95% confidence interval 0.982 to 0.998, p = 0.01). However, no association was noted between creatinine clearance and the incidence of adverse events among patients who received fluvastatin (hazard ratio 1.0, 95% confidence interval 0.99 to 1.0, p = 0.63). No further deterioration in creatinine clearance was observed during follow-up, regardless of baseline renal function or allocated treatment. Occurrence of adverse events was not related to changes in renal function during follow-up. Fluvastatin therapy markedly decreased the risk of coronary atherosclerotic events after percutaneous intervention in patients who had lower values of creatinine clearance at baseline. The benefit of fluvastatin was unrelated to any effect on renal function.