New Insight of Methylenetetrahydrofolate Reductase (MTHFR) C677T Gene Polymorphisms, and Serum Electrolytes in Cardiac Syndrome X Patients

Background: Cardiac Syndrome X (CSX) is a condition affecting the cardiovascular system with a significant degree of morbidity. Diagnosis and treatment are challenging when the cause is unclear. Subsequently, a molecular marker for screening of people with CSX is highly recommended. The present study evaluated the association between MTHFR C677T gene polymorphism among Sudanese patients with CSX. Materials and Methods: A total of 100 subjects were enrolled. Venous blood sample was collected from each participant in Ethylene Diamine Tetracetic Acid (EDTA) containers. DNA was extracted from blood samples using guanidine chloride method and MTHFR mutation was detected by PCR-restriction fragment polymorphism (PCR-RFLP). Statistical package for social sciences (SPSS) was used to analyze data. Results: Most patients 30(60%) were females, their age ranged between 30-60 with mean age 44.98±7.34 SD. MTHFR 677CT genotype frequency was statistically significant (P≤0.014), where 10(20%) had 677CT and 1(2%) had 677TT among patients group respectively compared to control individuals who had only 2(4%) 677CT. T alleles were significantly more frequent among our participant than C alleles. There is insignificant slightly decreased (2.4 ±2.8, and 2.5±3.2) in serum magnesium levels among patients compared to control respectively, as well as random blood glucose. Elevated mean levels of total cholesterol, and HDL among patients (182 ±18.1, and 49.7±7.1) vs (180 ±20.3, and 46.6 ±11.3) among control group, all findings were statistically non-significant. Slightly decrease in magnesium level (2.2 ±2.1, vs 2.9 ±0.8) among heterozygous CT genotypes compared to homozygous genotypes. Conclusion: MTHFR C677T is linked to CSX in the Sudanese population, and serum magnesium level was slightly decreased among heterozygous MTHFR C677T. Furthermore, the mutation could be used as a disease molecular screening technique.

AKT-mTOR Signaling-Mediated Rescue of PRKAG2 R302Q Mutant-Induced Familial Hypertrophic Cardiomyopathy by Treatment with β-AR Blocker Metoprolol

PRKAG2 cardiac syndrome, as a common form of metabolic hypertrophic cardiomyopathy (HCM) caused by mutations in PRKAG2 gene, often shows myocardial hypertrophy and abnormal glycogen deposition in cardiomyocytes. However, it remains incurable due to lacking of a management guideline for treatment. Herein, a β1-AR blocker Metoprolol was applied to 5 patients with PRKAG2 cardiac syndrome identified from a PRKAG2 R302Q mutant family, resulting in significantly postponed progression of cardiac hypertrophy. Overexpression of PRKAG2 R302Q in primary cardiomyocytes increased the activity of AMPK, induced cellular hypertrophy and glycogen storage, and promoted the phosphorylation levels of AKT-mTOR signaling. Application of either β1-AR blocker metoprolol or protein kinase A (PKA) inhibitor H89 to the cardiomyocytes rescued the HCM-like phenotypes induced by PRKAG2 R302Q, including suppression of both AKT-mTOR phosphorylation and AMPK activity. In conclusion, the current study not only determined the mechanism regulating HCM induced by PRKAG2 R302Q mutant, but also demonstrated a therapeutic strategy using β1-AR blocker to treat the patients with PRKAG2 cardiac syndrome.

Vegetative Indices in Assessing Effectiveness of the Photobioacoustic Complex in Children with the Vegetative Nervous System Somatoform Dysfunction, often Suffering from Acute Recurrent Infections

Photobioacoustic methods of complex exposure allow correcting vegetative, vascular-cardiac disorders in children with autonomicnervous system somatoform dysfunction syndrome (ANSSDS) without pharmacological load. Aim. To optimize the treatment of children with somatoform vegetative dysfunction (ANSSDS), often suffering from recurrent infections,using physiotherapy methods.The aim of the study was to optimize the treatment of children with somatoform vegetativedysfunction, often suffering from recurrentinfections, using physiotherapy methods. Material and methods. The study included 140 children with autonomic nervous system somatoform dysfunction syndrome (ANSSDS),often suffering from recurrent infection. For the first time, clinical complaints, functional (ECG and cardiointerval recording KIR)and vegetative indicators (Kerdo, Hildebrandt index, Biend, Baoev-Parin) before/after application of the innovative photobioacousticcomplex, including: BАС-BFB-bioacoustic effects on the head and LLLR on the projection of the cubital region and thymus were analyzed.The duration of the procedure was 30 minutes and the course of treatment was 10 procedures. Before and after the procedures,vegetative indices and indicators of myocardial bioelectrogenesis were examined, comparing them with the norm in healthy children. Results. 35% of children were diagnosed with parasympathicotonia (sympathetic imbalance -SI); 54.1% – sympathetic (SA) and10.9% – mixed (etonia – E) type of vegetative dystonia. There were reveled gender-age differences in subjective complaints of childrenwith ANSSDS, whose index vegetative indicators were correlated with the type of vegetative support. Children with SA were 2.5 timesmore likely to be diagnosed with cardiac syndrome and elevated blood pressure; in children with SI – 3.5 times more often detected:gastric, astheenoeurotic syndrome and allergic diseases; in children with E: asthenonevrotic, neurosis-like disorders and sleep disturbancesthat were differentiated after the use of photobioacoustic complex. Complaints and vegetative indices in children with SI andE were corrected more significantly than in SA. Conclusion. Evaluation of vegetative indicators in children 7-12 years with ANSSDS, often suffering from recurrent infection, allows topersonify treatment programs and reduce the level of acute recurrent morbidity by 2.5 times.

Cerebral-Cardiac Syndrome and Diabetes: Cardiac Damage After Ischemic Stroke in Diabetic State

Cerebral-cardiac syndrome (CCS) refers to cardiac dysfunction following varying brain injuries. Ischemic stroke is strongly evidenced to induce CCS characterizing as arrhythmia, myocardial damage, and heart failure. CCS is attributed to be the second leading cause of death in the post-stroke stage; however, the responsible mechanisms are obscure. Studies indicated the possible mechanisms including insular cortex injury, autonomic imbalance, catecholamine surge, immune response, and systemic inflammation. Of note, the characteristics of the stroke population reveal a common comorbidity with diabetes. The close and causative correlation of diabetes and stroke directs the involvement of diabetes in CCS. Nevertheless, the role of diabetes and its corresponding molecular mechanisms in CCS have not been clarified. Here we conclude the features of CCS and the potential role of diabetes in CCS. Diabetes drives establish a “primed” inflammatory microenvironment and further induces severe systemic inflammation after stroke. The boosted inflammation is suspected to provoke cardiac pathological changes and hence exacerbate CCS. Importantly, as the key element of inflammation, NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome is indicated to play an important role in diabetes, stroke, and the sequential CCS. Overall, we characterize the corresponding role of diabetes in CCS and speculate a link of NLRP3 inflammasome between them.