Carvedilol-liposome interaction: evidence for strong association with the hydrophobic region of the lipid bilayers.

Carvedilol (Kredex, Coreg) is a multiple action antihypertensive drug that has been shown to protect cell membranes from lipid peroxidative damages. In this study the physical and structural effects of carvedilol on lipid bilayers are investigated by fluorescence techniques, differential scanning calorimetry and other physical methods. Carvedilol binds to liposomal membranes (9:1 DMPC:DMPG) strongly with an apparent binding constant on the order of 10(4) M-1 in PBS (pH 7.4). The characteristic changes in its intrinsic fluorescence properties when bound to liposomes suggest that this compound is situated in a non-polar environment. The Stern-Volmer and bimolecular quenching constants, determined using nitrate as the fluorescence quencher, for the free and bound carvedilol indicate that the carbazole moiety is at a depth of > 11 A in the lipid bilayer. Fluorescence anisotropy measurements show that, unlike the membrane probes DPH and TMA-DPH, carvedilol is relatively mobile, and does not have a rigidly-defined molecular orientation in the bilayers. Differential scanning calorimetry results indicate that carvedilol is an effective membrane "fluidizer' as it dose-dependently lowers the gel to liquid crystalline transition temperature and broadens the endothermic transition. Comparative studies of interactions of carbazole, 4-OH carbazole and carvedilol with the model liposomal membranes reveal a possible role of membrane-partitioning in their antioxidant efficacy. These findings are discussed in perspective with the membrane biophysical properties of different classes of therapeutic significant lipid antioxidants in mind.

Thrombin-induced platelet malondialdehyde (MDA) formation in normal subjects and in women taking oral contraceptives.

Thrombin-induced platelet malondialdehyde (MDA) production and platelet count were studied in 82 male and 74 female healthy blood donors. 37 women on oral contraceptives (OC) had significantly lower values of MDA production than women who were not using the pill. There were no statistically significant differences of MDA production in women on a low dose estrogen, a medium dose, and a relatively high dose. Males had significantly higher values than females. In 15 further subjects (5 males, 5 OC-users, 5 OC-nonusers) the kinetics of MDA formation was determined by using increasing doses of thrombin. No significant differences could be found. Platelet count in women on OCs was lightly increased, but the difference was not significant.

Oxidative pentose phosphate pathway and pyridine nucleotides in relation to heartwood formation in Robinia pseudoacacia L.

Most tree species show in the inner parts of their woody axes often a dark colored zone, the heartwood. Its formation is a genetically determined, programmed cell death which is characterized by the activation of metabolic pathways which lead to the formation of phenolic heartwood extractives. In the present paper we report on the key position of the oxidative pentose phosphate pathway (OPP) for this process. The OPP plays a crucial role in anabolic processes and is involved in the interconversion and rearrangements of sugar-phosphates with the net production of NADPH. In tissues of Robinia pseudoacacia L. which are transferred to heartwood, enhanced activities of glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) are present. A consequence of these increased enzyme activities is a shift in the pyridine nucleotide pool towards NADP+NADPH at the expense of NAD+NADH. These alterations in the metabolism and the redox status probably provide precursors and reduction equivalents being required for the synthesis of heartwood phenolics. The non heartwood forming species Acer pseudoplatanus L. shows neither a radial gradient nor seasonal changes in the amounts of pyridine nucleotides across the trunkwood. The results are discussed in connection with programmed cell death, mitochondrial activity, and heartwood formation.

Natural and Chernobyl-caused radioactivity in mushrooms, mosses and soil-samples of defined biotops in SW Bavaria.

Different mushrooms, mosses and corresponding soil samples have been collected mainly from two sites in the alpine region of southwestern Bavaria. At the end of the growthseason, September 1986, gamma spectroscopic analysis showed that the moss-, mould, and needle-layer contained considerably more 134Cs and 137Cs activity per unit fresh weight than eight different species of mushroom. These two isotopes were carried into the biotop mainly as a consequence of the Chernobyl accident. 131J could not be found any more in the samples ca. 5-6 months after the catastrophe. The activity of the cesium isotopes decreased with increasing soil depth. In the mushrooms the activity was relatively high in Xerocomus badius and surprisingly low in Boletus edulis; samples of the latter and of Cantharellus cibarius collected in September 1985 (before the accident) and kept deep frozen contained almost identical amounts of 137Cs as those collected from August to October 1986. Mushrooms contained considerably more of the natural isotope 40K than the needlelayers and the soil samples in the neighbourhood. In all mushrooms except Xerocomus badius the activity of 40K was generally higher than the 137Cs activity. The results indicate that except Xerocomus badius the analyzed mushrooms do not actively take up Cs from the soil, in contrast to K.

Radioactivity in mushrooms, mosses and soil samples of defined biotops in SW Bavaria-two years after "Chernobyl".

Mushrooms, the moos/grass layer and soil samples have been collected in autumn 1987 from two sites in SW-Bavaria in continuation of a former investigation (Elstner et al. 1987). There were still relatively high amounts of 137Cs and 134Cs in all samples. The ratio 137Cs/134Cs changed according to the different half-life times of the two radioisotopes, indicating in nearly all cases the Chernobyl accident as source. The distribution of the radioisotopes within the mushroom populations shows considerable variation, even within the same species and location. Besides 137Cs, 134Cs and 40K no other radioisotopes were detected.

Micellar aggregation of poloxamer 213 and its interaction with cholesterol derivatives.

The micellar properties of Poloxamer 213 (1), a Pluronic copolymer shown to affect lipid absorption and serum cholesterol level in experimental animals, are investigated by surface tension measurements, photon correlation spectroscopy (PCS), Reichardt's dye solubilization technique, differential scanning calorimetry (DSC), electron paramagnetic resonance (EPR) spectrometry, and fluorescence spectroscopy. The clear inflection point at 3 x 10(-6) M (25 degrees C) observed in the surface tension-concentration curve may not represent the CMC for the formation of multimolecular aggregates. In the 10(-4) to 10(-2) M concentration range, the temperature-dependent transition (as the concentration of 1 increases) from the larger (hydrodynamic radius, Rh approximately 20-40 nm), highly hydrated aggregates to the contracted (Rh approximately 6-7 nm), less polar form occurs as a discontinuity. This process is endothermic, with an average delta H of 34.5 kcal/mol. At 25 degrees C, both the 25-(NBD-methylamino)-27-norcholesterol (fluorescence probe) and 3-Doxyl-5 alpha-cholestane (EPR spin probe) begin to show significant interaction with 1 in the 10(-3) M range. The sequestration of the fluorescent cholesterol probe by 1 aggregates begins at approximately 2 x 10(-4) M at 35 degrees C. Analysis of EPR and fluorescence data indicates that the cholesterol analogues are in a nonpolar micellar environment of low fluidity. The significance and implication of the data are discussed in the context of the hypothesized cholesterol sequestration by 1 under physiological conditions.

Automated spectrophotometric assay of cefazolin.

An automated, stability-indicating, UV spectrophotometric assay for cefazolin is presented. The method employs a reaction with hydroxylamine and derives its stability-indicating power through comparison of reacted and unreacted aliquots of the sample. A double-probe sampling procedure is used. Good agreement with microbiological assays is obtained, and the coefficient of variation is about 1%.

Aridicins, novel glycopeptide antibiotics. II. Isolation and characterization.

A new antibacterial antibiotic complex, aridicin, was produced by a new genus, Kibdelosporangium aridum (SK&F-AAD-216). The individual factors, aridicins A, B and C, were isolated from the fermentation broth by an Amberlite XAD-7 resin extraction and purified by preparative reversed phase HPLC. The aridicins were found to be novel members of the glycopeptide class of antibiotics as exemplified by ristocetin and vancomycin, based on chemical and spectroscopic data, their molecular weights as determined by FAB mass spectrometry (1,786, 1,800 and 1,814), the detection of actinoidinic acid in their acid hydrolysates, and detailed TLC and HPLC comparisons with representative members of this class.

Alteration of physiological parameters in needles of cloned spruce trees (Picea abies (L.) Karst.) by ozone and acid mist.

Three-year-old clonal spruce trees, kept in growth chambers, were treated with ozone and acid mist during a period of 14 months. One half of the trees were grown on an acidic sandy soil, the other half on a calcareous soil rich in carbonate. At the end of the fumigation period, carbohydrates (glucose, fructose, sucrose, raffinose, starch, glucose-1-phosphate and fructose-6-phosphate) and parameters of the energy status (ATP-, AdN-(ATP + ADP + AMP)- levels, ATP/ADP-ratios and adenylate-energy-charge-(AEC)-values) were determined in the current-year's needles. The results indicate that the metabolic status of a plant tissue is not only influenced by the nature of the air pollutants. Soil factors play an important role in metabolic changes within the plant and are thus of relevance in the manifestation of damage symptoms.

Microbial associations in gut systems of wood- and bark-inhabiting longhorned beetles [Coleoptera: Cerambycidae].

Using fluorescence in situ hybridization (FISH) techniques and PCR-based rDNA sequencing, gut microflora in the larvae of bark- and wood-inhabiting cerambycid beetles (Rhagium inquisitor, Tetropium castaneum, Plagionotus arcuatus and Leptura rubra [Coleoptera: Cerambycidae]) was investigated. A total of 12 novel ascomycetous yeast strains were isolated from the gut content. Panfungal and strain-specific oligonucleotide probes identified two yeast strains as Candida rhagii and Candida shehatae, which were colonizing specialized organs (mycetomes) adhering to the gut of R. inquisitor and L. rubra larvae, respectively. Fragments containing these organisms were constantly being released from the mycetomes into the gut lumen. Whereas the mycetome symbiont of T. castaneum could not be identified, all larvae of this species harbored an additional bacterial endocytobiont in their gut epithelium. This novel gammaproteobacterium belonged to the Sodalis clade of insect symbionts, which includes the secondary endosymbiont of tsetse flies (Sodalis glossinidius) and the Sitophilus oryzae primary endosymbiont (SOPE). Extracellular gut flora of the investigated cerambycid larvae was comprised of Alpha-, Beta-, and Gammaproteobacteria, Actinobacteria, Firmicutes, Verrucomicrobia and Acidobacteria. However, the individual composition among investigated larvae was highly variable and supposedly depended on individual host nutrition.

Acute effects of desipramine and clomipramine on pituitary-adrenal axis in man.

Brain neurotransmitters play an essential role in central regulation of hypothalamic factors which stimulate or inhibit the secretion of pituitary hormones. Insight in this complex system might be obtained by analysing changes in pituitary and peripheral hormone secretion following the administration of neuroactive drugs which influence the action of neurotransmitters. Desipramine is well-known to inhibit presynaptic norepinephrine reuptake, clomipramine on the other hand interferes with the serotoninergic system. In 15 male volunteers, the effects of single-dose administration of each drug were studied in comparison to placebo. Basal concentrations of ACTH and cortisol, as well as the rise of both hormones following insulin-induced hypoglycemia, were studied. Basal cortisol values and the response to hypoglycemia were not affected by either pharmacon in this study. Slight differences could be seen in the ACTH responses, which were however not significant.

Semiautomated turbidimetric microbiological assay for determination of cefazolin.

The Autoturb System, a semiautomated system for photometric bioassay, was used to determine cefazolin content. Suitable conditions for the assay using Streptococcus faecalis ATCC 10541 as the indicator organism included a medium pH of 6.0 to 7.0 and an incubation time of 3 to 3.5 h at 36 C. Multiple independent assays of samples from a common batch showed the test to be highly reproducible. Accuracy of the turbidimetric assay was evaluated by comparing data obtained from a chemical (hydroxylamine) and a biological (disk diffusion) assay. The available data show the turbidimetric assay to be a rapid, accurate, and reproducible method for determining the biological activity of cefazolin samples.

Case report: simple renal cyst in child.

A case of a large renal cyst of the right kidney suggesting a nephroblastoma is reported. Preoperative differentiation was diffucult.