SGLT2 inhibitors: a focus on cardiac benefits and potential mechanisms

Heart Failure Reviews - This paper highlights the cardioprotective potential of sodium-glucose cotransporter 2 inhibitors (SLGT2i), as well as several most discussed mechanisms responsible for...     

Association of the −262C/T polymorphism in the catalase gene promoter with carotid atherosclerosis in Slovenian patients with type 2 diabetes

Genetic variations of the antioxidant enzymes may influence the susceptibility to oxidative stress and consequently the development and progression of diabetic complications. The aim of the current study was to test the association between the −262C/T polymorphism in the catalase gene promoter and carotid atherosclerosis in Slovenian patients with type 2 diabetes. Two-hundred and eighty six diabetics and 150 healthy controls were enrolled in the study. Carotid atherosclerosis was quantified ultrasonographiocally by carotid intima-media thickness (CITM), plaque score and plaque type. Genotypes were determined using the real-time PCR. Fibrinogen concentration showed a borderline statistically significant difference due to catalase genotypes (p=0,05). No difference in clinical characteristics, CIMT, plaque stability or plaque score was observed. Logistic regression model adjusted for age, gender, smoking, BMI, lipid parameters and duration of hypertension and diabetes showed significant association of T allele and lower risk for higher plaque score (OR=0,25; p=0,025). No association with CIMT>1mm and unstable plaques was observed. T allele of −262C/T is associated with lower risk for higher plaque score but it did not affect clinical parameters, CIMT and plaque stability. Whether this polymorphism can be used as a genetic marker for advanced carotid atherosclerosis in diabetic patients needs to be evaluated in the future.     

The role of α1 and α5 subunit-containing GABAA receptors in motor impairment induced by benzodiazepines in rats

Benzodiazepines negatively affect motor coordination and balance and produce myorelaxation. The aim of the present study was to examine the extent to which populations of γ-aminobutyric acid A (GABAA) receptors containing α1 and α5 subunits contribute to these motor-impairing effects in rats. We used the nonselective agonist diazepam and the α1-selective agonist zolpidem, as well as nonselective, α1-subunit and α5-subunit-selective antagonists flumazenil, βCCt, and XLi093, respectively. Ataxia and muscle relaxation were assessed by rotarod and grip strength tests performed 20 min after intraperitoneal treatment. Diazepam (2 mg/kg) induced significant ataxia and muscle relaxation, which were completely prevented by pretreatment with flumazenil (10 mg/kg) and βCCt (20 mg/kg). XLi093 antagonized the myorelaxant, but not the ataxic actions of diazepam. All three doses of zolpidem (1, 2, and 5 mg/kg) produced ataxia, but only the highest dose (5 mg/kg) significantly decreased the grip strength. These effects of zolpidem were reversed by βCCt at doses of 5 and 10 mg/kg, respectively. The present study demonstrates that α1 GABAA receptors mediate ataxia and indirectly contribute to myorelaxation in rats, whereas α5 GABAA receptors contribute significantly, although not dominantly, to muscle relaxation but not ataxia.     

Benefit of early abdominal ultrasonography in non-surgical patients admitted to the emergency department: a pilot study

Purpose  

Ultrasonography plays a decisive role in emergency patients. The primary aim of this study is to assess whether early emergency ultrasonography alters the length of stay.     

Basilar artery occlusive disease in stroke survivors in a multiethnic population

Objectives

To describe clinical, radiological findings, and outcome in a multiethnic population of stroke survivors with basilar artery occlusive disease (BAOC).

Methods

Forty patients with infarcts in the basilar artery (BA) territory, alive 30 days after the ictus, participated in the study. BA stenosis (>50%) or occlusion was shown by magnetic resonance or digital subtraction angiography in all patients. Demographical, clinical and radiological characteristics were described. Modified Rankin Scale (MRS) scores at 30 days and 6 months after the ischemic event were evaluated. Association between demographical, clinical, radiological features and outcome were analyzed with Chi-square and Fisher's exact tests. MRS scores at 30 days and 6 months were compared with the Wilcoxon test.

Results

Sixty percent of the patients were men, and 33% were Afro-Brazilian. Mean age was 55.8 ± 12.9 years. Most (90%) had multiple vascular risk factors. Stroke was preceded by TIA in 48% of the patients, and 80% had a history of arterial hypertension. The most common neurological symptom was vertigo/dizziness (60%) and the sign, hemiparesis (60%). Most of the infarcts were located in the pons (85%) and the BA middle third was the most frequently affected segment (33%). BA occlusion occurred in 58% of the patients. More severe vascular occlusive lesions were present in Whites (p = 0.002) and in patients with involvement of the middle third of the BA (p = 0.021). Large-artery atherosclerosis was the most common stroke etiology (88%) and was more frequent in older patients (p < 0.001). Most patients were treated with anticoagulation. MRS scores improved significantly at 6 months (p < 0.001); at this time, 78% of the patients had MRS scores between 0 and 2.

Conclusions

We observed different results compared with other series: greater proportion of Afro-descendents, higher frequency of atherosclerosis and BA occlusion. Rates of preceding TIAs and good outcome at 6 months were similar to previously published data. These results represent a step forward towards understanding BAOC in a multiethnic context.     

The influence of climate change on human cardiovascular function

Abstract

Climate change is considered to have great impact on human health. The heat waves have been associated with excess morbidity and mortality of cardiovascular diseases (CVD) across various populations and geographic locations. Important role in the heat-induced cardiovascular damage has endothelial dysfunction. It has been noticed that hot weather can impair tone and structure of the blood vessels via interfering with variety of biological factors such as nitric oxide synthesize, cytokine production and systemic inflammation. Also, due to dehydration and increased blood viscosity, by promoting thrombogenesis, heat has important impact on patients with atherosclerosis. During chronic exposure to the cold or hot weather cardiovascular function can be decreased, leading to a higher risk of developing heart attack, malignant cardiac arrhythmias, thromboembolic diseases and heat-induced sepsis like shock. It has been shown that changes in the ambient temperature through increasing blood pressure, blood viscosity, and heart rate, contribute to the cardiovascular mortality. The majority of deaths due to heat waves especially affect individuals with preexisting chronic CVD. This population can experience a decline in the health status, since extreme ambient temperature affects pharmacokinetic parameters of many cardiovascular drugs. Increased mortality from ischemic or hemorrhagic stroke can also be related to extreme temperature variations. On a cellular level, higher ambient temperature can limit storage of ATP and O₂ increase amount of free radicals and toxic substances and induce neuronal apoptotic signal transduction, which all can lead to a stroke. Preserving cardiovascular function in context of extreme climate changing tends to be particularly challenging.     

Evaluation of genotoxic potential of avarol,avarone, and its methoxy and methylamino derivatives in prokaryotic and eukaryotic test models

In this study, mutagenic and genotoxic potential of anti-tumor compounds avarol, avarone, and its derivatives 3′-methoxyavarone, 4′-(methylamino)avarone and 3′-(methylamino)avarone was evaluated and compared to cytostatics commonly used in chemotherapy (5-fluorouracil, etoposid, and cisplatin). Mutagenic potential of selected hydroquinone and quinones was assessed in prokaryotic model by the SOS/umuC assay in Salmonella typhimurium TA1535/pSK1002. Genotoxic potential was also assessed in eukaryotic models using comet assay in human fetal lung cell line (MRC-5), human adenocarcinoma epithelial cell line (A549), and in human peripheral blood cells (HPBC). The results indicated that avarol and avarone do not exert mutagenic/genotoxic potential. Among the studied avarone derivatives, mutagenic potential was detected by SOS/umuC test for 3′-(methylamino)avarone, but only after metabolic activation. The results of comet assay indicated that 3′-methoxyavarone and 3′-(methylamino)avarone have a significant impact on the level of DNA damage in the MRC-5 cell line. Genotoxic potential was not observed in A549 cells or HPBC probably due to a different uptake rate for the compounds and lower in metabolism rate within these cells.