[Carbamazepine in modern toxicological casuistry at Department of Forensic Medicine of Medical University of Gdansk in the years 1996-2001]. / Karbamazepina we wspólczesnej kazuistyce toksykologicznej Zakladu Medycyny Sadowej Akademii Medycznej w Gdansku w latach 1996-2001.

In this paper the authors presented 20 cases of death of individuals diagnosed at Department of Forensic Medicine of Medical University of Gdansk in the years 1996-2001. In all cases carbamazepine was found in post-mortem material collected from the deceased during autopsy. 14 deaths resulted from intoxication after overdose of drugs for the purpose of committing suicide. In the other cases carbamazepine did not have on influence on the cause of death. The subject of the chemo-toxicological analysis were blood and urine samples and also specimens of the stomach with its contents, liver, kidney, brain and lung specimens collected during autopsy. TLC, GC-FID, GC-MS, TLC-UV were used as diagnostic tools. Determined carbamazepine concentrations fluctuated between 1.5 to 78.6 micrograms/ml in the blood.

[Group intoxication with 2-ethoxyethanol as an ethanol substitute]. / Grupowe zatrucie 2-etoksyetanolem jako zamiennikiem etanolu.

In this paper the authors presented the group 2-ethoxyethanol intoxication of 8 young men aged between 20 to 22. 50-100 ml of pure compound (diluted with water) was administrated as a drink. In this paper symptoms of acute intoxication to this compound were presented. GC-FID and GC-MS were used as diagnostic tools. The obtained results were compared with the data from available literature.

p53 activates the mitochondrial death pathway and apoptosis of ventricular myocytes independent of de novo gene transcription.

The tumor suppressor p53 is known to regulate gene transcription and apoptosis in mammalian cells. In the present study we ascertain whether these events are mutually dependent and obligatorily linked for induction of apoptosis of ventricular myocytes. Adenovirus mediated gene delivery of wild p53 (p53WT) or a mutant form of p53 (p53MT) defective for gene transcription to ventricular myocytes was confirmed by Western blot analysis. A significant increase in the p53 dependent genes Bax and MDM2 was observed with p53WT but not p53MT. Nuclear DNA visualized by agarose gel electrophoresis revealed nucleosomal DNA laddering in the presence of either p53 protein. Apoptosis was substantiated by Hoechst 33258 nuclear staining. Perturbations to mitochondria consistent with the mitochondrial death pathway, including loss of mitochondrial transmembrane potential Delta(psi)m and cytochrome c release were observed with p53WT and p53MT. An increase in caspase 3-like activity was noted with either p53WT or p53MT protein that was suppressed by the caspase 3 inhibitor Ac-DEVD-CHO. To our knowledge the experiments described here provide the first indication that p53 activates the mitochondrial death pathway and provokes apoptosis of ventricular myocytes independent of DNA binding and de novo gene activation.

Serpin protein CrmA suppresses hypoxia-mediated apoptosis of ventricular myocytes.

BACKGROUND: In this study, we ascertain whether caspase 8 activation and mitochondrial defects underlie apoptosis of ventricular myocytes during hypoxia. As an approach to circumvent the potential shortcomings surrounding the limited permeability and short half-life of the synthetic peptide inhibitors designed to block caspase activation, we constructed a replication-defective adenovirus encoding the serpin caspase inhibitor protein CrmA to ensure efficient and continual inhibition of caspase 8 activity during chronic hypoxia. METHODS AND RESULTS: In contrast to normoxic cells, oxygen deprivation of postnatal ventricular myocytes for 24 hours resulted in a 9-fold increase (P<0.05) in apoptosis as determined by Hoechst 33258 staining and nucleosomal DNA laddering. Moreover, hypoxia provoked a 1.5-fold increase (P<0.01) in caspase 8-like activity. Furthermore, hypoxia provoked perturbations to mitochondria consistent with the mitochondrial death pathway, including permeability transition pore (PT) opening, loss of mitochondrial membrane potential ((m)), and cytochrome c release. Importantly, CrmA suppressed caspase 8 activity, PT pore changes, loss of (m), and apoptosis but had no effect on hypoxia-mediated cytochrome c release. Furthermore, Bongkrekic acid, an inhibitor of PT pore, prevented hypoxia-induced PT pore changes, loss of (m), and apoptosis but had no effect on hypoxia-mediated cytochrome c release. CONCLUSIONS: To our knowledge, we provide the first direct evidence for the operation of CrmA as an antiapoptotic factor in ventricular myocytes during prolonged durations of hypoxia. Furthermore, our data suggest that perturbations to mitochondria including PT pore changes and (m) loss are caspase-regulated events that appear to be separable from cytochrome c release.

Apoptosis in ventricular myocytes: the role of tumor suppressor proteins.

Apoptosis or programmed cell death is an important physiologic event crucial for the selective removal of damaged or unwanted cells from body tissues. In the cardiovascular system, apoptosis has been observed in the vasculature and myocardium. Untimely or inappropriate myocardial cell loss through an apoptotic process may contribute to ventricular remodeling and the ultimate demise of ventricular function following injury. Therapeutic interventions designed to modulate or prevent myocardial apoptotic cell loss may therefore prove beneficial in maintaining cardiac function. Incite into the molecular mechanisms that govern apoptosis in mammalian cells has led to the identification of several key factors that promote or prevent the apoptotic process. In this report, we discuss putative regulators of cardiac cell apoptosis with specific reference to the tumor suppressor proteins, p53 and Rb. The interplay between these factors, as well as the anti-apoptotic molecules related to the Bcl-2 the family are discussed in the context of the heart under normal and disease conditions.