Aims: The role of nitric oxide (NO) in heart failure (HF) is complex and remains controversial. We tested the hypothesis that the role of NO in isolated atria and cardiomyocytes is altered in isoproterenol-induced HF. Methods and results: Rats received isoproterenol (ISO, 5 mg/kg/day, intraperitoneally) or vehicle for 1 week. Haemodynamic parameters were obtained by left ventricular catheterization. Effects of NOS inhibition on isolated atria and on electrically paced left ventricular myocytes were determined. Additionally, expressions of nitric oxide synthases and their allosteric modulators hsp90, caveolin-1, and caveolin-3 proteins in the left ventricles were measured. ISO increased left ventricular mass by 33% and decreased indices of left ventricular systolic and diastolic function dp/dtmin and dp/dtmax (both P < 0.05). Isolated atria from HF rats had a lower spontaneous beating rate (P < 0.05). NOS inhibition by L-NAME increased basal frequency and attenuated the positive chronotropic effect of beta-adrenergic stimulation in the HF group (P < 0.05). Ventricular myocytes from failing hearts had impaired cell shortening. L-NAME decreased contractility of control, but not failing myocytes. Left ventricular expressions of eNOS, hsp90, iNOS, but not nNOS or caveolins, were increased. Conclusion: Despite the increased capacity for NO synthesis in isoproterenol-induced HF, NO does not sustain contractility of failing myocytes. NO may contribute to the decreased basal heart rate and it may accelerate beta-adrenergic stimulation of chronotropy.

Metformin (MTF) is a widely used drug for the treatment of diabetes mellitus type 2 (DM2) and frequently used as an adjuvant therapy for polycystic ovarian syndrome, metabolic syndrome, and in some cases also tuberculosis. Its protective effect on the cardiovascular system has also been described. Recently, MTF was subjected to various analyzes and studies that showed its beneficial effects in cancer treatment such as reducing cancer cell proliferation, reducing tumor growth, inducing apoptosis, reducing cancer risk in diabetic patients, or reducing likelihood of relapse. One of the MTF’s mechanisms of action is the activation of adenosine-monophosphate-activated protein kinase (AMPK). Several studies have shown that AMPK/mammalian target of rapamycin (mTOR) pathway has anticancer effect in vivo and in vitro. The aim of this review is to present the anticancer activity of MTF highlighting the importance of the AMPK/mTOR pathway in the cancer process.

Background: Patients with atrial fibrillation (AF) have a higher risk of fatal complications (e.g., stroke). This investigation was performed as an observational retrospective cohort study includes 137 patients (age 61 ± 15; 34.3% women) with a primary diagnosis of AF (paroxysmal, persistent, and permanent). Methods: We collected information about the drug therapy, comorbidities and survival of AF patients and determined their congestive heart failure, hypertension, age, diabetes mellitus, prior stroke or TIA or thromboembolism, vascular disease, age, sex category (CHA₂DS₂-VASc) scores. Statistical analysis identified patients with high CHA₂DS₂-VASc scores and defined the predictive value of individual parameters, or their combination, with regards to the outcomes of stroke and mortality. Results: CHA₂DS₂-VASc scores identified 43.8% of the patients as low to intermediate risk (score 0–1) and 56.2% of the patients as high risk (score ≥2). Increasing CHA₂DS₂-VASc scores were not only accompanied by an increase in the incidence of stroke (P _trend < .001) but also by an increase in the 3 to 5 years mortality (P = .005). Comparison of anticoagulation and anti-aggregation treatment between the 3 groups of AF did not show any significant statistical difference. Highly significant predictors of death were the CHA₂DS₂-VASc score (OR 1.71, 95% CI 1.10–2.67, P < .017) as well as other risk factors not included in the CHA₂DS₂-VASc score such as valvular heart disease (OR 5.04, 95% CI 1.10-23.10, P = .037), hyperlipidemia (OR 4.82, 95% CI 1.03–22.63, P = .046) and chronic renal failure (OR 14.21, 95% CI 2.41–83.91, P = .003). The type of AF type did not affect survival (P = .158) nor the incidence of stroke (P = .466). Patients with paroxysmal AF were linked to significantly lower frequencies of ischemic heart disease (P < .0001), vascular disease (P = .002), diabetes mellitus (P = .047), valvular heart disease (P = .03) and heart failure/left ventricular dysfunction (P = .015). Conclusion: The CHA₂DS₂-VASc score correctly predicted the patients at high-risk for 3 to 5 years mortality and confirmed its significant predictive value in the patients with AF.

Background: Once-daily treatment formulation is associated with better adherence in comparison to more complex medication regimens. The study aimed to detect the extent of adherence to pharmacotherapy in Parkinson disease (PD) patients who take a minimum of three daily doses of drugs, and to identify factors associated with lower levels of adherence. Methods: The cohort was selected from non-demented PD patients. The 8-Item Morisky Medication Adherence Scale (MMAS-8), 8-Item Parkinson's Disease Questionnaire (PDQ-8), Geriatric Depression Scale (GDS), Non-Motor Symptom Assessment Scale (NMSS), 9-Item Wearing-off Questionnaire (WOQ-9), MDS-UPDRS III (motor examination), and IV (motor complications) scales were used in this study. Results: From a total of 124 subjects, 33.9% reported a high level of adherence, 29.8% reported a medium level of adherence, and 36.3% reported a low level of adherence to their pharmacotherapy. The level of non-adherence correlated with gender, longer disease duration, higher scores of PDQ-8, NMSS, WOQ-9, and MDS-UPDRS IV. Detailed analysis of NMSS demonstrated a correlation between the level of adherence and domains sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, and urinary symptoms. Independent risk factors for non-adherence were excessive daytime sleepiness, anhedonia, and forgetfulness. Conclusion: Non-adherence to more complicated medication regimens is frequent in PD patients and is associated with gender, longer PD duration, poorer quality of life, frequency and severity of non-motor symptoms, and more severe motor and non-motor fluctuations. Non-adherence was predicted by non-motor symptoms including fatigue, mood disturbances, and subjective cognitive complaints.

Parkinson disease (PD) is the second most common neurodegenerative disease with various motor and nonmotor symptoms. Progressive course of PD requires frequent medication adjustments. Various combinations of drugs and dose regimens could be used to control symptoms. Thus, not surprisingly, adherence to pharmacotherapy is frequently suboptimal in these patients having negative effect on motor control and patient's quality of life. In this article, we offer up-to-date review of adherence in PD compared with other chronic conditions. In addition, we summarize factors influencing level of adherence, ways of measuring, and methods of adherence optimization. For the review of adherence in PD, a literature search was undertaken using PubMed database and relevant search terms. Articles were screened for suitability and data relevance. PubMed and Scopus databases were systematically searched in 2016 and data extraction was a multistep process based on the PRISMA Guidelines. According to the recent data, sufficient control of motor symptoms and adequate quality of life are primary goals in the treatment of PD. Adherence to pharmacotherapy play a key role in this process, thus the medication should be tailored for each patient. In order to improve level of suboptimal adherence, these patients should have got recommended various dosing devices or alarms. Good communication with the patients and their relatives or caregivers is also essential.

Objectives: Many studies indicate the involvement of transient receptor potential (TRP) channels in the development of heart hypertrophy. However, the data is often conflicted and has originated in animal models. Here, we provide systematic analysis of TRP channels expression in human failing myocardium. Methods and results: Left-ventricular tissue samples were isolated from explanted hearts of NYHA III-IV patients undergoing heart transplants (n = 43). Quantitative real-time PCR was performed to assess the mRNA levels of TRPC, TRPM and TRPV channels. Analysis of functional, clinical and biochemical data was used to confirm an end-stage heart failure diagnosis. Compared to myocardium samples from healthy donor hearts (n = 5), we detected a distinct increase in the expression of TRPC1, TRPC5, TRPM4 and TRPM7, and decreased expression of TRPC4 and TRPV2. These changes were not dependent on gender, clinical or biochemical parameters, nor functional parameters of the heart. We detected, however, a significant correlation of TRPC1 and MEF2c expression. Conclusions: The end-stage heart failure displays distinct expressional changes of TRP channels. Our findings provide a systematic description of TRP channel expression in human heart failure. The results highlight the complex interplay between TRP channels and the need for deeper analysis of early stages of hypertrophy and heart failure development.