Dipeptidyl peptidase-4 inhibitors as new tools for cardioprotection.

Previous studies have demonstrated that individuals with type 2 diabetes mellitus (T2DM) have a two- to fourfold propensity to develop cardiovascular disease (CVD) than nondiabetic population, making CVD a major cause of death and disability among people with T2DM. The present treatment options for management of diabetes propose the earlier and more frequent use of new antidiabetic drugs that could control hyperglycaemia and reduce the risk of cardiovascular events. Findings from basic and clinical studies pointed out DPP-4 inhibitors as potentially novel pharmacological tools for cardioprotection. There is a growing body of evidence suggesting that these drugs have ability to protect the heart against acute ischaemia-reperfusion injury as well as reduce the size of infarction. Consequently, the prevention of degradation of the incretin hormones by the use of DPP-4 inhibitors represents a new strategy in the treatment of patients with T2DM and reduction of CV events in these patients. Here, we discuss the cardioprotective effects of DPP-4 inhibitors as well as proposed pathways that these hypoglycaemic agents target in the cardiovascular system.

The Role of Cardiac N-Methyl-D-Aspartate Receptors in Heart Conditioning-Effects on Heart Function and Oxidative Stress.

As well as the most known role of N-methyl-D-aspartate receptors (NMDARs) in the nervous system, there is a plethora of evidence that NMDARs are also present in the cardiovascular system where they participate in various physiological processes, as well as pathological conditions. The aim of this study was to assess the effects of preconditioning and postconditioning of isolated rat heart with NMDAR agonists and antagonists on heart function and release of oxidative stress biomarkers. The hearts of male Wistar albino rats were subjected to global ischemia for 20 min, followed by 30 min of reperfusion, using the Langendorff technique, and cardiodynamic parameters were determined during the subsequent preconditioning with the NMDAR agonists glutamate (100 µmol/L) and (RS)-(Tetrazol-5-yl)glycine (5 µmol/L) and the NMDAR antagonists memantine (100 µmol/L) and MK-801 (30 µmol/L). In the postconditioning group, the hearts were perfused with the same dose of drugs during the first 3 min of reperfusion. The oxidative stress biomarkers were determined spectrophotometrically in samples of coronary venous effluent. The NMDAR antagonists, especially MK-801, applied in postconditioning had a marked antioxidative effect with a most pronounced protective effect. The results from this study suggest that NMDARs could be a potential therapeutic target in the prevention and treatment of ischemic and reperfusion injury of the heart.

Preconditioning with PDE1 Inhibitors and Moderate-Intensity Training Positively Affect Systemic Redox State of Rats.

Taken into consideration that oxidative stress response after preconditioning with phosphodiesterase inhibitors (PDEIs) and moderate physical activity has still not been clarified, the aim of this study was to assess the effects of PDEIs alone or in combination with physical activity, on systemic redox status. The study was carried out on 96 male Wistar albino rats classified into two groups. The first group included animals exposed only to pharmacological preconditioning (PreC) maneuver (sedentary control (CTRL, 1 ml/day saline, n = 12), nicardipine (6 mg/kg/day of NIC, n = 12), vinpocetine (10 mg/kg/day of VIN, n = 12), and nimodipine (NIM 10 mg/kg/day of, n = 12). The second included animals exposed to preconditioning with moderate-intensity training (MIT) on treadmill for 8 weeks. After 5 weeks from the start of training, the animals were divided into four subgroups depending on the medication to be used for pharmacological PreC: moderate-intensity training (MIT+ 1 ml/day saline, n = 12), nicardipine (MIT+ 6 mg/kg/day of NIC, n = 12), vinpocetine (MIT+ 10 mg/kg/day of VIN, n = 12), and nimodipine (MIT+ 10 mg/kg/day of NIM, n = 12). After three weeks of pharmacological preconditioning, the animals were sacrificed. The following oxidative stress parameters were measured spectrophotometrically: nitrites (NO2 -), superoxide anion radical (O2 -), hydrogen peroxide (H2O2), index of lipid peroxidation (TBARS), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH). Our results showed that PDE1 and MIT preconditioning decreased the release of prooxidants and improved the activity of antioxidant enzymes thus preventing systemic oxidative stress.

The influence of folic acid-induced acute kidney injury on cardiac function and redox status in rats.

The aim of this study was to evaluate the influence of acute kidney injury caused by high doses of folic acid on cardiac function and markers of oxidative stress in serum and isolated rat heart. Isolated hearts of Wistar albino rats (divided into two groups: control and folic acid group) were perfused according to Langendorff technique at basal coronary perfusion pressure CPP of 70 cm H2O. After a stabilization period, CPP was lowered to 60 cm H2O and then gradually increased to 80, 100, 120 and finally decreased to 40 cm H2O in order to establish coronary autoregulation. For each perfusion pressure value, the left ventricular function parameters were determined. Samples of coronary venous effluent were collected for determination of coronary flow and biomarkers of oxidative stress. The blood samples were collected in order to examine the values of serum urea, creatinine, Na, K, and parameters of oxidative stress and antioxidant defense system. Heart and kidney tissue samples were collected for histopathological examination. Folic acid group showed reduction of systolic and diastolic left ventricular pressure and increase of coronary flow and minimum left ventricular pressure development rate. In coronary flow, folic acid group showed increased levels of TBARS and reduction of H2O2 and NO2-. Serum ROS concentrations were lower in rats treated with folic acid, particularly levels of TBARS and NO2- in which values were significantly lower. The parameters of systemic antioxidative stress were at significantly high levels especially SOD and GSH. This study is the experimental confirmation of cardio-renal syndrome type 3, which represents the acute kidney injury that causes a damage of a heart function. The data suggest that negative effects of acute kidney injury on myocardium do not necessarily involve oxidative stress, which may lead to future investigations which will be based on inflammation as a one of the important factors in the organ crosstalk.

The perfusion of cisplatin and cisplatin structural analogues through the isolated rat heart: The effects on coronary flow and cardiodynamic parameters.

The therapeutic use of cisplatin for the treatment of solid tumours is associated with organ toxicity. Amongst those, the cardiotoxicity is an occasional but very serious and severe side effect. To prevent or reduce these negative effects, many cisplatin analogues have been synthesized and evaluated in terms of being a less toxic and more effective agent. In present study, we examined the effects of cisplatin and its three analogues in the isolated rat heart to determine whether changes in the structure of the platinum complexes (changing of carrier ligands - ethylenediamine; 1,2-diaminocyclohexane; 2,2':6',2''-terpyridine) can influence their cardiotoxic effects. The results of our research indicate that the introduction of aromatic rings in the structure of the platinum complexes has a negative influence on the heart function. Conversely, the other two examined complexes had less negative effects on heart function compared to cisplatin. Our findings may be of interest for a possible synthetic strategy of introducing a carrier ligand that will exert a less cardiotoxic effect.

Cisplatin and cisplatin analogues perfusion through isolated rat heart: the effects of acute application on oxidative stress biomarkers.

Drug-induced oxidative stress can occur in numerous tissues and organ systems (liver, kidney, ear, nervous system, and cardiovascular system). Cancer therapy with cisplatin is associated with side effects to which oxidative stress may contribute. We have compared the influences of cisplatin (reference compound) and its' analogues (dichloro(1,2-diaminocyclohexane)platinum(II) and chloro(2,2':6',2″-terpyridine)platinum(II)) in a model of isolated rat heart using the Langendorff technique. The production of oxidative stress biomarkers, antioxidant enzymes, myocardial damage, and expression of Bax, OH-1, and SODs were studied. Cisplatin and the analogues were perfused at concentration of 10-6 and 10-5 M during 30 min. The results of this study showed that examined platinum complexes had different ability to induce oxidative stress of isolated perfused rat heart. Varying the carrier ligands, such as 1,2-diaminocyclohexane and 2,2':6',2″-terpyridine, related to amino ligands (cisplatin) directly influenced the strength to induce production of oxidative stress biomarkers. Introducing 2,2':6',2″-terpyridine ligands provoked the smallest changes in antioxidant enzymes activity, lipid peroxidation, and expression of heme oxygenase-1, that undoubtedly indicated that this complex had the lowest impact on redox status in heart tissue. These findings may be useful in synthesis of novel platinum analogues with lower potential for oxidative stress induction. However, the fact that platinum complexes could induce toxic effects in the heart by other mechanisms should be taken into the consideration.

Quality of life of schizophrenic patients treated with haloperidol depot and injection preparation of long-lasting risperidone.

INTRODUCTION: In the last decades psychiatric patients' quality of life attracts great attention of researchers. Improving the quality of life of schizophrenic patients is increasingly becoming an imperative in pharmacological therapy. OBJECTIVE: Analysis of certain aspects of quality of life in patients with schizophrenia treated with depot formulations of a typical antipsychotic (haloperidol) and injection preparation of a long-acting atypical antipsychotic (risperidone). METHODS: Research was conducted as a cross-sectional study that included 60 patients of both genders. Examinees diagnosed with schizophrenia (ICD-10, F20.0-F20.9) were divided into two groups: the group of patients that received haloperidol depot (n = 30) and the group of patients that received injection preparation of long-acting risperidone (n = 30). In order to assess the quality of life, social functioning scale (SFS), satisfaction with life scale (SWLS), and short version of World Health Organization quality of life scale (WHO-QoL-Brief) were applied. RESULTS: Results showed statistically significant differences when it comes to social activity and satisfaction with life in favour of patients treated with injection preparation of long-acting risperidone. Examinees from this group were much more satisfied with themselves, their health and sleep compared to those on haloperidol depot. There was no statistically significant difference found on the quality of life scale. CONCLUSIONS: Applying the scales for the assessment of the quality of life of schizophrenic patients in terms of psychosocial functioning, statistically significant difference between groups was found. Results showed higher scores in the group of patients treated with injection preparation of long-acting risperidone concerning social activities and life satisfaction.

Differentiation between opiate addicts in relation to judicial problems.

INTRODUCTION: Some research results point to significant benefit in the use of methadone substitution treatment in reduction of criminogenic activities in opiate addicts, as in positive affect on their somatic and mental state. OBJECTIVE: The objective of the study was to indicate factors which lead to criminogenic activities in addicts with judicial problems before entering substitute, methadone program. METHODS: Addicts were divided into two groups: addicts who had judicial problems before they entered substitution methadone program (group A-46 addicts) and addicts withoutjudicial problems (group B-20 addicts). A questionnaire containing basic data about the addicts in the treatment program (Pompidou questionnaire) was for questioning. RESULTS: A statistically significant difference was recorded related to the way of taking PAS. The largest number of examinees from the group A took primal PAS intravenously (41; 89.1%), while from the group B 11 took it intravenously (55.0%). The majority of examinees in the group A committed the first criminal act before taking PAS (psychoactive substances) (19; 41.3%), then after taking so-called harder PAS (16; 34.8%), and finally after taking the so-called lighter PAS (11; 23.9%). In somewhat over half of the examinees in the group A (24; 52.2%) the measure of juvenile court was imposed. A suspended sentence was passed upon 19 (41.3%) examinee, then prison sentence in 16 (34.8%), multiple prison sentences in 6 (13.0%) and misdemeanour in 4 (8.7%). CONCLUSION: Future research at our centre should show the efficiency of methadone program in a decrease of risky behaviour, degree of criminogenic activity and judicial problems, improvement of life quality, as well as show the ways for preventive acting.