Temporal pattern of herpes simplex virus type 1 infection and cell death in the mouse brain stem: influence of guanosine nucleoside analogues

Levels of bystander death occurring in herpes simplex virus type 1 (HSV-1)-infected mouse brain stems were studied, as well as the extent to which bystander death is influenced by guanosine nucleoside analogue treatment. Consecutive sections from brain stems of HSV-1-infected mice were stained alternately for (i) viral infection and (ii) cell death (TUNEL assay). Virus antigen was detectable in brain stems on day 3 of infection, while TUNEL staining was comparatively lower. An increase in the extent of TUNEL staining was observed on day 4 of infection. Despite this increase, however, the ratio of TUNEL-stained to infection marker-stained tissue still indicated that the amount of TUNEL staining remained lower than infection staining at this time point. On days 5 and 6 of infection, TUNEL staining continued to increase and the TUNEL/infection marker ratio switched on day 6 in favour of excess TUNEL staining, which was observed in and around the foci of infection, suggesting bystander death. The excess TUNEL staining on day 6 of infection was further increased on treatment with antivirals. The significance and implications of these results are discussed with respect to the nature and mechanism of action of the TUNEL assay, dynamics of primary HSV-1 infection, immunological influences and potential effects of antiviral treatment. The potential problems of the TUNEL assay are considered in the context of viral infection and the TUNEL assay, in combination with infection marker staining, may potentially provide a model system for quantitative analysis of true bystander death during HSV infection in vivo.     

Rewarding effects of the optical isomers of 3,4-methylenedioxy-methylamphetamine ('Ecstasy') and 3,4-methylenedioxy-ethylamphetamine ('Eve') measured by conditioned place preference in rats

3,4-methylenedioxy-methylamphetamine (MDMA) (‘Ecstasy’) and its analogue 3,4-methylenedioxy-methylamphetamine (MDE) (‘Eve’) are well known illicit street drugs mainly abused by young people. In spite of the actual research going on, the classification of their abuse potential remains unclear. Since secondary reinforcers are the main factors responsible for craving and relapse, the aim of our study was to assess the potency of MDMA and MDE in a second order reinforcement paradigm, i.e. conditioned place preference (CPP). For the general assessment of our study conditions, we compared MDMA with amphetamine. Unexpectedly, no significant CPP for MDMA was found in contrast to amphetamine. Detailed analysis of current literature led us to the working hypothesis that social environment is crucial for the development of CPP. In a subsequent experiment we tested the influence of housing conditions on CPP using MDMA and demonstrated that isolated animals show significant CPP compared to group-housed ones. In order to better understand the rewarding mechanisms of Ecstasy-derivatives, we tested both the racemic drugs and the pure isomers in the CPP paradigm. Both MDMA's optical isomers and racemic MDMA showed significant CPP without notable differences, while MDE and its isomers completely failed to show any significant CPP. In conclusion, the mechanism by which MDMA induces addiction is much more complicated than assumed so far and more pronounced in isolated animals. The fact that both optical isomers of MDMA led to CPP implies that at least two pathways by which MDMA induces craving behaviour exist.     

Cellular mechanisms of T cell mediated drug hypersensitivity

Noncovalent drug presentation leads to the activation of drug-specific T cells. In some patients with hypersensitivity, such a response occurs within hours even upon the first exposure to the drug. Thus, the reaction to the drug might not be due to a classical, primary response, but rather mediated by existing, preactivated T cells that are cross specific for the drug, and have an additional (peptide) specificity as well.     

Haarnadelgegenstromprinzip als Grundlage der Harnkonzentrierung in der Niere

Ohne ZusammenfassungVortrag anläßlich der Überreichung der Urkunde eines Dr. med. h. c. der medizinischen Fakultät der Universität Kiel, gehalten vor der Kieler Medizinischen Gesellschaft und dem Ortsverband Kiel der Gesellschaft Deutscher Chemiker am 5. Mai 1959.Aus dem Physikalisch-Chemischen Institut der Universität Basel, Direktor: Prof. Dr.W. Kuhn.     

Messungen zum Aggregationsverhalten perfluorierter Alkansäuren

With the use of various techniques an attempt was made to characterize the aggregates that exist in micellar surfactant solutions of salts of the perfluornonanoic acid. The cmc values of the investigated systems were determined by conductivity and surface tension measurements. Conclusions about the shape of the micellar aggregates were drawn from rheologic and electric birefringence measurements. For the lithium, the ammonium and the tetramethylammonium surfactants the existence of normal micelles with spherical shape and with all surfactant ions lying at the micellar surface was found. The perfluornonanoate surfactants with the ammonium counterions that are partially substituted by alkyl groups showed in all investigations a behaviour that was different from the normal case. It was postulated that these solutions contain emulsion-droplet-like giant micelles with the surfactant ions and counterions solubilized as ion pairs in the interior of the micelles. Some of these giant micelles do not have spherical shape; these solutions showed electric birefringence. In most cases the giant micelles disappeared at higher temperatures. Only normal small micelles with spherical symmetry could then be detected and the measured values were again in the range for values of normal C₈-perfluordetergents. On the basis of the investigated systems reasons and models for the formation of giant micelles are discussed.     

Molecular analysis of streptogramin resistance in enterococci

The new semi-synthetic streptogramin antibiotic combination quinupristin/dalfopristin (Synercid) is a promising alternative for a treatment of infections with multiple resistant gram-positive pathogens, e.g. glycopeptide- and multi-resistant Enterococcus faecium. Streptogramins consist of two unrelated compounds, a streptogramin A and B, which act synergistically when given in combination. Mechanisms conferring resistance against both components are essential for resistance against the combination in E. faecium. In this species resistance to streptogramin A compounds is mediated via related acetyltransferases VatD and VatE. Resistance against streptogramins B is either encoded by the widespread ermB gene cluster conferring resistance to macrolide-lincosamide-streptogramin B antibiotics or via expression of the vgbA gene, which encodes a staphylococcal-type lactonase. E. faecalis is intrinsically resistant to streptogramins. Due to a wide use of streptogramins (virginiamycins S/M) in commercial animal farming a reservoir of streptogramin-resistant E. faecium isolates had already been selected. Determinants for streptogramin resistance are localized on plasmids that can be transferred into an E. faecium recipient both in vitro in filter-matings and in vivo in the digestive tracts of rats. Hybridization and sequencing experiments revealed a linkage of resistance determinants for streptogramins A and B on definite plasmid fragments.     

Chemotherapieinduzierte Veränderungen bei hochmalignen zentralen Osteosarkomen

High-grade central osteosarcomas are the most frequent malignant bone neoplasms in childhood and adolescence. Their prognosis has been substantially improved using neoadjuvant chemotherapy. The morphological examination of surgical specimens reveals important information regarding the success of treatment. The histological determined degree of regression represents one of the most reliable therapy-related prognostical factor. Thus pathological analysis of the surgical specimens is of great importance notwithstanding the improved clinical and radiological diagnostic of osteosarcoma.