Histoenzymatische Untersuchungen über das Verhalten einiger Enzyme in Nebennieren nach lokaler und Ganzkörperbestrahlung

Zusammenfassung In dieser Arbeit beschÄftigen wir uns mit dem Verhalten der BernsteinsÄure-Dehydrogenase, der DPNH-Diaphorase, der Adenosintriphosphatase und der alkalischen Phosphatase in den Nebennieren gesunder Meerschweinchen sowie Versuchstieren, die einer Ganzkörper- und Lokalbestrahlung mit Dosen von je 400 r unterworfen wurden.Die Untersuchungen ergaben 24 Stunden nach Ganzkörperbestrahlung einen Anstieg, nach 4 Tagen ein Absinken der Atmungsfermente. Nach 11 Tagen waren die Reaktionen bei den Versuchstieren individuell verschieden.Die ATP-ase und die alkalische Phosphatase steigerte ihre AktivitÄt in den ersten Tagen nach der Bestrahlung, dann traf eine AktivitÄtssenkung ein.Bei lokaler Bestrahlung konnte in den Nebennieren ein AktivitÄtsanstieg der ATP-ase, alkalischen Phosphatase, DPNH-Diaphorase und eine AktivitÄtssenkung der BernsteinsÄure-Dehydrogenase festgestellt werden.Man nimmt an, da\ die VerÄnderungen die Folge einer Stress-Reaktion auf die Nebennieren sind, die noch durch extrasuprarenale Faktoren, wie Eiwei\spaltprodukte und elektrolytische Störungen dm Gesamtkörper beschleunigt werden.Herrn Professor Dr. A. Pischinger zum 65. Geburtstag gewidmet.     

Metal Cations Defibrillize the Amyloid Beta-Protein Fibrils

Amyloid beta-protein (A) is the major constituent of amyloid fibrils composing -amyloid plaques and cerebrovascular amyloid in Alzheimer's disease (AD). We studied the effect of metal cations on preformed fibrils of synthetic A by Thioflavin T (ThT) fluorescence spectroscopy and electronmicroscopy (EM) in negative staining. The amount of cross beta-pleated sheet structure of A 1–40 fibrils was found to decrease by metal cations in a concentration-dependent manner as measured by ThT fluorescence spectroscopy. The order of defibrillization of A 1–40 fibrils by metal cations was: Ca²⁺ and Zn²⁺ (IC₅₀ = 100 M) > Mg²⁺ (IC₅₀ = 300 M) > Al³⁺ (IC₅₀ =1.1 mM). EM analysis in negative staining showed that A 1–40 fibrils in the absence of cations were organized in a fine network with a little or no amorphous material. The addition of Ca²⁺, Mg²⁺, and Zn²⁺ to preformed A 1–40 fibrils defibrillized the fibrils or converted them into short rods or to amorphous material. Al³⁺ was less effective, and reduced the fibril network by about 80 % of that in the absence of any metal cation. Studies with A 1–42 showed that this peptide forms more dense network of fibrils as compared to A 1–40. Both ThT fluorescence spectroscopy and EM showed that similar to A 1–40, A 1–42 fibrils are also defibrillized in the presence of millimolar concentrations of Ca²⁺. These studies suggest that metal cations can defibrillize the fibrils of synthetic A.     

Conformation of dioxopiperazines,II. CNDO/2 quantum mechanical calculations on conformational preferences in cyclo (glycyl-L-alanyl), cyclo(glycyl-L-valyl), and both epimers of cyclo-di-(alanyl)

Conformational energy calculations, aimed at verification of the suitability of the semiempirical molecular orbital CNDO/2 method for conformational elucidations in cyclic dipeptides formed from amino acids with aliphatic side chains, have been carried out. The results obtained for four dioxopiperazines [DOP; cyclo(Glycyl-L-Alanyl), cyclo(Glycyl-L-Valyl), and both epimers of cyclo-di-(Alanyl)] point out very good agreement with experimental premises. The latter include (1) the preference of the cis-peptide bonds for being nonplanar, which results in twisted-boat conformations of the DOP ring; (2) greater stability of conformers with a side chain oriented axially over those with a side chain oriented equatorially; (3) the preference of cyclo(Gly-Val) for assuming a folded conformation with one of the side chain γ-methyl groups sticking over the DOP ring.     

Antibiotic tetaine — a selective inhibitor of chitin and mannoprotein biosynthesis in Candida albicans

The antibiotic tetaine inhibits in Candida albicans the biosynthesis of two important cell wall constituents, chitin and mannoprotein. This effect is a consequence of inactivation of the enzyme glucosamine-6-phosphate synthetase. Due to the lack of glucosamine-6-phosphate the effective secretion of mannoprotein enzymes, acid phosphatase and invertase, by Candida albicans spheroplasts is inhibited. In the presence of tetaine, probably a modified mannoprotein, lacking a branched polymannan, is synthesized. The antibiotic action decreases the viability of Candida albicans cells, especially that of mycelial forms of this fungus.Abbreviations GlcNAc N-acetyl-d-glucosamine - GlcN-6-P d-glucosamine-6-phosphate - ManNAc N-acetyl-d-mannosamine - -MM -methylmannoside - EGTA 1,2 di/2-aminoethoxy/ethane - N,N,N,N tetra-acetic acid     

In vitro mutagenic,antimutagenic, and antioxidant activities evaluation and biotransformation of some bioactive 4‐substituted 1‐(2‐methoxyphenyl)piperazine derivatives

In vitro mutagenic, antimutagenic, and antioxidant potency evaluation and biotransformation of six novel 4‐substituted 1‐(2‐methoxyphenyl)piperazine derivatives demonstrating antidepressant‐like activity were investigated. Mutagenic and antimutagenic properties were assessed using the Ames test; free radical scavenging activity was evaluated with 2,2‐diphenyl‐1‐picrylhydrazyl radical scavenging assay and biotransformation was performed with liver microsomes. It was found that all tested compounds are not mutagenic in bacterial strains TA100 and TA1535 and exhibit antimutagenic effects in the Ames test. Noteworthy, compounds possessing propyl linker between phenoxyl and N‐(2‐methoxyphenyl)piperazine displayed more pronounced antimutagenic properties than derivatives with ethoxyethyl linker. Additionally, compounds 2 and 6 in vitro biotransformation showed that primarily their hydroxylated or O‐dealkylated metabolites are formed. Some of the compounds exhibited intrinsic clearance values lower than those reported previously for antidepressant imipramine. To sum up, the results of the present study might represent a valuable step in designing and planning future studies with piperazine derivatives.     

Correlation between the extent of coronary atherosclerosis and lipid profile

Increased concentration of low density lipoprotein (LDL) cholesterol or decreased level of high density lipoprotein (HDL) cholesterol are important risk factors for coronary atherosclerosis. However, an independent association of triglycerides (TG) with atherosclerosis is uncertain.The aim of this prospective study was to evaluate the relationship between serum lipid levels and the extent of coronary atherosclerosis in patients with suspected coronary artery disease (CAD) and no previous myocardial infarction who were not treated with lipids lowering therapy or low-lipid diet.The study was conducted in 141 patients (53.6 ± 7.8 years old; 32 female) who underwent a routine coronary angiography for CAD diagnosis. A modified angiographic Gensini Score (GS) was used to reflect the extent of coronary atherosclerosis. Fasting serum lipid concentrations were determined using cholesterol esterase/peroxidase (CHOD/PAP) enzymatic method for total cholesterol and its fractions and lipase glycerol kinase (GPO/PAP) enzymatic method TG evaluation. The association of Gensini Score with variables characterising lipid profile was analysed with the use of Pearson correlation (r co-efficient; p value).GS was positively correlated with total cholesterol (r = 0.404; p < 0.001), LDL cholesterol (r = 0.484; p < 0.001) and TG (r = 0.235; p = 0.005). There was a negative correlation between Gensini Score and HDL cholesterol (r = –0.396; p < 0.001).In angina pectoris patients with no previous myocardial infarction, the extent of coronary atherosclerosis is positively correlated with pro-atherogenic lipids, i.e. total cholesterol, LDL cholesterol and TG and negatively correlated with antiatherogenic HDL cholesterol.