In vitro delineation of human brain-stem anatomy using a small resonator: correlation with macroscopic and histological findings.

Our purpose was to investigate the potential of an experimental animal coil using a commercial MRI unit to delineate the anatomical structure of the human brain stem. Three formaldehyde-fixed brain-stem specimens were examined by MRI and sectioned perpendicular to their longitudinal axis. The images were compared with gross anatomy and myelin-stained histological sections. Fibre tracts and nuclei which were not evident on examination of the unstained specimen were readily identified by MRI. Due to its inherent grey/white matter contrast, MRI with a high-resolution coil delineates anatomical structures in a way comparable to the myelin-stained histological sections. However, pigmented structures, readily visible on examination of the unstained specimen were discernible on neither MRI nor on myelin-stained sections. The excellent anatomical detail and grey/white matter contrast provided by these images could make MRI a useful adjunct to the pathologist investigating brain disease.

New NO-donors with antithrombotic and vasodilating activities, IX: Thiadiazole nitrosimines.

Twenty 1,3,4-thiadiazole-2-nitrosimines and two 1,2,4-thiadiazole-5-nitrosimines were synthesized and assayed in the Born-test for their antiplatelet activity. Only two 1,3,4-thiadiazoles inhibited the aggregation at IC50 < 10 mumol/L. In an in vivo thrombosis model only in arterioles a small inhibition of thrombus formation was observed. The poor test results correspond to a very high chemical stability of the titel nitrosimines.

New NO-donors with antithrombotic and vasodilating activities, VIII: Benzothiazole-2(3H)-nitrosimines.

Thirty title compounds were prepared and tested for their antiplatelet activity in the Born-test. Five nitrosimines inhibit the aggregation induced by collagen in concentrations below 10 mumol/L halfmaximally. Four compounds were investigated in an in vivo thrombosis model. An inhibition of thrombosis between 29 and 53% was observed in mesenteric arterioles of rats 2 h after p.o. administration (60 mg/kg). The effect in venoles was less pronounced (10-22%). For one compound these effects could still be demonstrated 4 h after oral application.

New NO-donors with antithrombotic and vasodilating activities, VII: Z/E-isomerism in thiazole- and 1,3,4-thiadiazole-2-nitrosimines.

In thiazole- (23 compounds) and 1,3,4-thiadiazole-2-nitrosimines (20 compounds) Z/E-isomers were described by 1H-NMR-spectroscopy. There is a mutual conversion of the isomers. The coalescence temp. (Tc) mostly is 310 K. In the thiazole series, however, for five compounds higher energy barriers are observed. This is due to substituents in 4-position with electron withdrawing properties. The Tc is increased when the compounds are dissolved in water instead of DMSO. Hereby it is concluded that the isomers have Ze or Ee configuration. It is made probable that the low field signal for the substituent in 3-position corresponds to the Ze-isomer, which has a slight preference. The free enthalpy of rotation, calculated approximately, is between 56.0 (1m) and 73.7 kJ/mol (1r).

New NO-donors with antithrombotic and vasodilating activities, VI: thiazole-2-nitrosimines.

24 new thiazole-2-nitrosimines were prepared and described by means of spectroscopical methods (NMR, IR, MS, UV). At pH 7 in cell free systems as well as in platelet rich plasma the compounds are stable against hydrolysis and do not react with the platelet glutathione. The chemical stability is underlined by the mass spectra: M+. is of high intensity and sometimes even forms the base peak (e.g. 8a). Thermal elimination of N2 is of minor importance. The =N-NO bond in solution is susceptible to cleavage by visible light. The metabolite so formed is able to inhibit the platelet aggregation induced by collagen (Born-test). Five compounds exhibit this activity in concentrations below 10 mumol/L (IC50). This is due to the release of a NO species, as could be demonstrated by the stimulation of soluble guanylate cyclase in a cell free system (e.g. 8a, KM = 72 mumol/L). In vivo the nitrosimines show antithrombotic properties. Two h after a single oral dose of 8g (60 mg/kg) a 57% inhibition of the laser induced thrombus formation in the mesenteric arterioles of rats is observed. After 8 h a 43% inhibition still is seen.

New NO-donors with antithrombotic and vasodilating activities, IV: Chemical reactivity of nitrosimines and its implications for their pharmacologic properties.

Nitrososydnone-5-imines and Thiazole-2-nitrosimines are susceptible to photolytic cleavage of the = N-NO bond. This can be achieved with a tungsten lamp. In water the corresponding syndnone imine salts are formed in 90% yield at 37 degrees C. Only at higher temp. (70 degrees C) ring opening is observed. In methanol about 25% of sydnones are obtained. On the other hand NO. and N2O were detected in the head space of the reaction vials when oxygen was excluded. The formation of N2O from nitrososydnone imine was increased up to elevenfold by glutathione while the amount of NO. was decreased. In the presence of light and thiols soluble guanylate cyclase (s-GC) was stimulated. The results suggest that the nitroxylate anion NO- plays an important role in the stimulation of s-GC.

Arrangement of prematurely condensed chromosomes in cultured cells and lymphocytes of the Indian muntjac.

Premature chromosome condensation (PCC) was induced in order to study the arrangement of muntjac chromosomes in the interphase nuclei of proliferating and resting cells with respect to their polarity and the spatial relationship between them. The data were compared with the situation in in situ fixed and colcemid blocked metaphases. It appears that in rapidly dividing cells almost all G1- and G2 interphase chromosomes exhibit the Rabl type polarized orientation. This pattern still predominates in G0 lymphocytes which may have been arrested at this stage for some months or even years. - The location of the small chromosome Y2 was found to be "central" in normal metaphases but "peripheral" in colcemid blocked mitoses. The behavior in the premature condensed chromosome preparations was intermediate. Measurements of centromere distances between all possible pairs of chromosomes as well as on the relative position of chromosomes in circular spreads revealed no evidence for homologous somatic association during interphase and metaphase or any other suprachromosomal ordering principle. Interphase chromosome orientation seems to be solely the result of chromosome arrangement of the foregoing anaphase. Association between heterochromatic regions or the nucleolus organizers did not substantially influence this pattern. There is no support for speculations that in mammalian cells close proximity of homologous sites is instrumental in functional cooperation.

[Clinical value of the dexamethasone-HCG test in females with hirsutism with special reference to 17-beta-hydroxyandrogens]. / Beitrag zur klinischen Wertigkeit des Dexamethason-HCG-Testes bei Frauen mit Hirsutismus unter besonderer Berücksichtigung der 17-Beta-Hydroxyandrogene.

The dexamethasone-hcg-test was administered to 34 hospitalized patients, aged 17 to 45, who were suffering from hirsutism in order to reveal the source of their androgen levels, which in most cases were elevated. In addition to the usual estimation of urinary 17-ketosteroids and urinary 17-OH-corticosteroids plasma 17-beta-hidroxiandrogens and androstendione were measured by RIA. The results of the tests varied to a high degree and could not be related to the clinical findings. The authors conclude that administration of dexamethasone-hcg-test is of small value in detecting the source of hirsutism.

Cytogenetic investigations in a new case of Bloom's syndrome.

Cytogenetic studies of an 8-year-old caucasian girl with typical but mild manifestation of Bloom's syndrome showed a characteristic increase of homologous chromatid translocations and prematurely condensed chromosomes. The average frequency of sister chromatid exchanges (SCE) in lymphocytes with 133 was much higher than in skin fibroblasts with 49. The inter- and intrachromosomal distributions of SCE in lymphocytes were analyzed.