Drug Candidate BGP-15 Prevents Isoproterenol-Induced Arrhythmias and Alters Heart Rate Variability (HRV) in Telemetry-Implanted Rats.

Multi-target drug candidate BGP-15 has shown cardioprotective and antiarrhythmic actions in diseased models. Here, we investigated the effects of BGP-15 on ECG and echocardiographic parameters, heart rate variability (HRV), and arrhythmia incidence in telemetry-implanted rats, under beta-adrenergic stimulation by isoproterenol (ISO). In total, 40 rats were implanted with radiotelemetry transmitters. First, dose escalation studies (40-160 mg/kg BGP-15), ECG parameters, and 24 h HRV parameters were assessed. After, rats were divided into Control, Control+BGP-15, ISO, and ISO+BGP-15 subgroups for 2 weeks. ECG recordings were obtained from conscious rats, arrhythmias and HRV parameters were assessed, and echocardiography was carried out. ISO-BGP-15 interaction was also evaluated on an isolated canine cardiomyocyte model. BGP-15 had no observable effects on the ECG waveforms; however, it decreased heart rate. HRV monitoring showed that BGP-15 increased RMSSD, SD1, and HF% parameters. BGP-15 failed to counteract 1 mg/kg ISO-induced tachycardia, but diminished the ECG of ischemia and suppressed ventricular arrhythmia incidence. Under echocardiography, after low-dose ISO injection, BGP-15 administration lowered HR and atrial velocities, and increased end-diastolic volume and ventricle relaxation, but did not counteract the positive inotropic effects of ISO. Two weeks of BGP-15 treatment also improved diastolic function in ISO-treated rats. In isolated cardiomyocytes, BGP-15 prevented 100 nM ISO-induced aftercontractions. Here, we show that BGP-15 increases vagally mediated HRV, reduces arrhythmogenesis, enhances left ventricle relaxation, and suppresses the aftercontractions of cardiomyocytes. As the drug is well tolerated, it may have a clinical value in preventing fatal arrhythmias.

[Health related quality of life and disease burden of patients with schizophrenia in Hungary]. / A szkizofreniaval elo betegek egeszseggel osszefuggo eletminosege es betegseg-terhe Magyarorszagon.

INTRODUCTION: According to the international literature disease burden of schizophrenia is substantial, however data from Eastern Central Europe is scarce. Our aim was to assess the quality of life and costs of patients with schizophrenia in Hungary. METHODS: A cross sectional questionnaire survey was performed in 3 hospital based psychiatry centres involving patients with schizophrenia. Demographics, disease severity (Clinical Global Impression, CGI), functional ability (Global Assessment of Functioning, GAF) and general health status (EQ-5D) was assessed. Health care utilisation and aids were surveyed for the past 12 months. Costing was performed from the societal perspective and human capital approach was applied. RESULTS: Altogether 78 patients (female 43.6%) were involved with a mean age of 44.2 (SD=13.1) years, disease duration was >10 years at 49 (62.8%) cases, 66 (84.6%) patients were disability pensioners. Distribution between CGI 3-4-5-6 levels were 12 (16%), 33 (43%), 21 (28%), 10 (13%) patients, respectively, mean GAF was 52.6 (SD=13.9). The average EQ-5D score was 0.64 (SD=0.3) and it was significantly worse than the age-matched general population's score in Hungary (p < 0.01). Mean yearly cost was 13 878 Euros/patient (conversion 1 Euro=280.6 HUF), the rate of direct medical,direct non-medical and indirect costs was 28.5%, 5.4% and 66.1%, respectively. Among direct costs hospitalisation and drug costs were dominant. Total cost correlates with disease severity (CGI). CONCLUSION: Schizophrenia leads to notable deterioration in health related quality of life and induce high costs to society, mainly due to the productivity loss of the patients. Nevertheless disease related costs in Hungary are lower than in economically more developed European countries. Our study offers basic data about disease burden of schizophrenia in Hungary to support clinical and health policy decision making.

Theory of mind and motion perception in schizophrenia.

This study investigated the relationship between theory of mind (ToM) deficits and visual perception in patients with schizophrenia (N=52; 17 remitted and unmedicated) compared with healthy controls (N=30). ToM was assessed with the Eyes Test, which asked participants to choose which of 4 words best described the mental state of a person whose eyes were depicted in a photograph. Visual perception was evaluated with form and motion coherence threshold measurements. Results revealed that patients with schizophrenia (both remitted and nonremitted) showed deficits on the Eyes Test and the motion coherence task. ToM dysfunctions were associated with higher motion coherence thresholds and more severe negative symptoms. This suggests that ToM deficits are related to motion perception dysfunctions, which indicates a possible role of motion-sensitive areas in the pathophysiology of schizophrenia.

[Learned equivalence in schizophrenia: novel method for the measurement of memory functions of the hippocampus and basal ganglia]. / Tanult ekvivalencia szkizofréniában: új módszer a hippocampalis és a basalis ganglionokhoz kapcsolódó memóriafunkciók mérésére.

The purpose of the present study was to investigate basal ganglia (BG) and medial temporal lobe (MTL) dependent learning in patients with schizophrenia. Acquired equivalence is a phenomenon in which prior training to treat two stimuli as equivalent (if two stimuli are associated with the same response) increases generalization between them. The learning of stimulus-response pairs is related to the BG, whereas the MTL system participates in stimulus generalization. Forty-three patients with DSM-IV schizophrenia and 28 matched healthy controls participated in the study. Volunteers received the acquired equivalence associative learning task (FISHES) during which associations between faces and pet fishes are learned. Results revealed that patients with schizophrenia showed a selective deficit on stimulus generalization, whereas stimulus-response learning was unaffected. The number of errors during stimulus-response learning correlated with the daily chlorpromazine-equivalent dose of antipsychotics. In conclusion, patients with schizophrenia showed deficits during MTL-dependent learning, but not during BG-dependent learning. High-dose first generation antipsychotics may disrupt BG-dependent learning by blocking dopaminergic neurotransmission in the nigro-striatal system.