Synthesis,X-ray crystal structures and biological activity of 16-amino-17-substituted-D-homo steroid derivatives

D-Homo derivatives in the androstane and estrane series, 12-19, were synthesized by a fragmentation-cyclization reaction of 16-oximino-17-hydroxy-17-substituted derivatives 3-9, or by cyclization of the corresponding D-seco derivatives 20-26. The structures were confirmed by X-ray analysis of compounds 12 and 16. Preliminary assessment of inhibitory effects of D-homo derivatives from androstane series towards aromatase, 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), 17 alpha-hydroxylase/C17-20 lyase (P450c17) and 17 beta-HSD indicated much lower inhibitory potential compared to previously tested activity of another type of D-modified steroids, namely D-seco derivatives. Also, assessment of potential antiestrogenic activity of derivatives from estrane series showed absence of such an activity.     

Radiographic changes in alveolar bone height on overdenture abutments: a longitudinal study

Objective: Stabilisation of partial dentures is an important part of prosthodontic treatment, particularly in patients with an excessive reduction in alveolar bone supporting their abutment teeth. In these cases, overdenture prostheses are one possible treatment choice. Background: The aim of this study was to evaluate the effects of overdentures on the condition of alveolar bone of the remaining teeth, and to evaluate the overdenture concept in the prosthetic treatment of partially edentulous patients. Materials and methods: The investigation was conducted on 22 patients during observation periods of 6 and 10 years. After preparation, all abutment teeth were provided with either amalgam restorations or gold copings. An overdenture in the lower jaw was fabricated for every patient. A special film holder was used to repeat the X‐ray procedure in every patient in the same manner. The radiographs were evaluated using the grid scale. The alveolar bone level of all remaining teeth was evaluated on dental films by measuring the distance between the root apex and coronal border of the alveolar bone. Results: A statistically significant difference (p < 0.01) was calculated 6 years after delivery stage between distal alveolar bone levels of experimental abutments under overdentures and the remaining teeth of the control group. Alveolar bone of abutment teeth was considerably preserved, particularly in seven patients observed 10 years after provision of their dentures. Conclusion: Within the limitation of this study, the validity of the overdenture treatment in partially edentulous patients is concluded. Good oral hygiene was crucial for the success of treatment with overdentures.     

Identification and Antimicrobial Susceptibility Testing of <Emphasis Type="Italic">Staphylococcus vitulinus</Emphasis> by the BD Phoenix Automated Microbiology System

This study evaluated the performance of the BD Phoenix system for the identification (ID) and antimicrobial susceptibility testing (AST) of Staphylococcus vitulinus. Of the 10 S. vitulinus isolates included in the study, 2 were obtained from the Czech Collection of Microorganisms, 5 from the environment, 2 from human clinical samples, and 1 from an animal source. The results of conventional biochemical and molecular tests were used for the reference method for ID, while antimicrobial susceptibility testing performed in accordance with Clinical and Laboratory Standards Institute recommendations and PCR for the mecA gene were the reference for AST. Three isolates were incorrectly identified by the BD Phoenix system; one of these was incorrectly identified to the genus level, and two to the species level. The results of AST by the BD Phoenix system were in agreement with those by the reference method used. While the results of susceptibility testing compared favorably, the 70% accuracy of the Phoenix system for identification of this unusual staphylococcal species was not fully satisfactory.     

Variability of the needle essential oils of Pinus peuce from different populations in Montenegro and Serbia

The essential-oil composition of Pinus peuce Griseb. is reported at the population level. Macedonian pine is endemic high-mountain Balkan pine relict of an anthropogenically reduced area, with large morphological diversity and insufficiently clear taxonomic position. In the pine-needle terpene profile of two populations from Montenegro and one from Serbia, 78 compounds were detected, 56 of which are identified (Table 3). The dominant constituents were alpha-pinene (36.5%) and germacrene D (11.4%). The following 20 additional components were found to be present in medium-to-high amounts (0.5-10%): camphene (8.5%), bornyl acetate (6.8%), beta-pinene (6.8%), beta-caryophyllene (5.2%), beta-phellandrene (4.7%), terpinen-4-ol acetate (1.6%), (E)-hex-2-enal (1.5%), alpha-muurolene (1.2%), beta-gurjunene (1.1%), beta-myrcene (1.0%), alpha-terpinyl acetate (0.9%), alpha-phellandrene (0.8%), delta-cadinene (0.8%), alpha-humulene (0.8%), sabinene (0.7%), aromadendrene (0.6%), alpha-thujene (0.6%), gamma-muurolene (0.6%), gamma-cadinene (0.6%), alpha-terpinolene (0.5%), and one unknown component (0.5%). The similarity of the populations and the within-population variability were visualized by principle-component analysis (PCA) and genetic analysis of selected terpenes in 90 tree samples. Our study suggests a closer connection between populations II and III compared to population I. Based on the profile of the main terpene components, the studied populations are more similar to populations from Kosovo and Greece than to the population from Mt. Mokra (Montenegro) and the population in France.     

Factors influencing cell fatty acid composition and A40926 antibiotic complex production in <Emphasis Type="Italic">Nonomuraea</Emphasis> sp. ATCC 39727

A40926 is a glycopeptide antibiotic complex consisting of several structurally related factors. It is produced by fermentation of Nonomuraea sp. ATCC 39727 and the complex components differ in the structure of the fatty acid moiety linked to the aminoglucuronic acid unit. In previous work, we observed that the production of single factors in glycopeptide antibiotic complexes could be selectively enhanced by the addition of suitable precursors to the culture medium. In this contribution, we examine the effects of branched amino acid addition to fermentation of Nonomuraea sp. in a chemically defined minimal medium. The changes in the composition of cell fatty acids correlate to the fatty acid distribution within the A40926 complex in diverse cultivation conditions. Nonomuraea sp. prefers isobutyric, butyric and propionic acids as initiators of fatty acid biosynthesis. The relative amount of the produced fatty acids is significantly influenced by the availability of intermediates or final products from the amino acid catabolic pathways. Antibiotic complex composition closely reflects the cell fatty acid pattern, in agreement with the assumption that the antibiotic fatty acid moieties are synthesized by shortening the chain of cell fatty acids.     

Synthesis and biological evaluation of a series of A,B-ring modified 16,17-secoandrostane derivatives

The starting compound for the synthesis of 16,17-secoandrostane derivatives with the 4-en-3-on, 1,4-dien-3-on, 4,6-dien-3-on, and 1,4,6-trien-3-on systems was 3β-hydroxy-17-methyl-16,17-secoandrost-5-en-16-nitrile-17-one (1), the Oppenauer oxidation of which yielded the corresponding 4-en-3-one derivative 2. Dehydrogenation of compound 2 with the aid of 2,3,5,6-tetrachloro-1,4-benzoquinone (chloranil) gave the three products: 17-methyl-16,17-secoandrosta-1,4-dien-3,17-dione-16-nitrile (3), 17-methyl-16,17-secoandrosta-4,6-dien-3,17-dione-16-nitrile (4), and 17-methyl-16,17-secoandrosta-1,4,6-trien-3,17-dione-16-nitrile (5). On the other hand, epoxidation of compound 2 resulted in a mixture of α and β isomers of 4,5-epoxy-17-methyl-16,17-secoandrosta-3,17-dione-16-nitrile (6 and 7). Opening of the oxirane rings of the mixture of 6 and 7 by the action of formic acid yielded the 4-hydroxy-4-en derivative 8. Antiaromatase activity and in vitro cytotoxicity against three tumor cell lines (human breast adenocarcinoma ER+, MCF-7, human breast adenocarcinoma ER−, MDA-MB-231, and prostate cancer PC3) of selected compounds were evaluated. Compound 2 exhibited a relatively strong inhibition of aromatase and extremely potent cytotoxicity against PC3 cells. Compound 8 showed satisfactory cytotoxicity against MCF-7 cells.     

Sugar uptake in a 2-deoxy-d-glucose resistant mutant ofSaccharomyces cerevisiae

Summary The non-metabolizable and toxic glucose analogue 2-deoxy-d-glucose (2-DOG) has been widely employed to screen for regulatory mutants which lack catabolite repression. A number of yeast mutants resistant to 2-DOG have recently been isolated in this laboratory. One such mutant, derived from aSaccharomyces cerevisiae haploid strain, was demonstrated to be derepressed for maltose, galactose and sucrose uptake. Furthermore, kinetic analysis of glucose transport suggested that the high affinity glucose transport system was also derepressed in the mutant strain. In addition, the mutant had an increased intracellular concentration of trehalose relative to the parental strain. These results indicate that the 2-DOG resistant mutant is defective in general glucose repression.     

2-epi-fortimicin B. Participation of 1-N-benzyloxycarbonylamino and 1-acetamido groups in solvolysis of 2-O-(methylsulfonyl)fortimicin B derivatives

Synthesis of 2-epi-fortimicin B has been accomplished by processes involving solvolyses of both 1-N-benzyloxycarbonyl- and 1-N-acetyl-2-O-(methylsulfonyl)fortimicins B, which occur with participation of the carbonyl oxygen atoms of the 1-N-acyl groups. The results illustrate both the greater effectiveness of acetamido groups in neighboring-group participation relative to benzyloxycarbonylamino groups, and the sensitivity of the nature of the products to the reaction conditions.     

Daily administration of interleukin-18 causes myocardial dysfunction in healthy mice

Although increased levels of circulating interleukin (IL)-18 have been demonstrated in patients with cardiovascular diseases, the functional consequences of chronically increased circulating IL-18 with respect to myocardial function have not been defined. Thus we aimed to examine the effects of chronic IL-18 exposure on left ventricular (LV) function in healthy mice. Moreover, to clarify whether IL-18 has direct effects on the cardiomyocyte, we examined effects of IL-18 on cardiomyocytes in vitro. After 7 days of daily intraperitoneal injections of 0.5 microg IL-18 in healthy mice, a 40% (P < 0.05) reduction in the LV maximal positive derivative, a 25% (P < 0.05) reduction in the LV maximal rate of pressure decay, and a 2.8-fold (P < 0.001) increase in the LV end-diastolic pressure were measured, consistent with myocardial dysfunction. Furthermore, we measured a 75% (P < 0.05) reduction in beta-adrenergic responsiveness to isoproterenol. IL-18 induced myocardial hypertrophy, and there was a 2.9-fold increase (P < 0.05) in atrial natriuretic peptide mRNA expression in the LV myocardium. In vitro examinations of isolated adult rat cardiomyocytes being stimulated with IL-18 (0.1 microg/ml) exhibited an increase in peak Ca2+ transients (P < 0.05) and in diastolic Ca2+ concentrations (P < 0.05). In conclusion, this study shows that daily administration of IL-18 in healthy mice causes LV myocardial dysfunction and blunted beta-adrenergic responsiveness to isoproterenol. A direct effect of IL-18 on the cardiomyocyte in vitro was demonstrated, suggesting that IL-18 reduces the responsiveness of the myofilaments to Ca2+. Finally, induction of myocardial hypertrophy by IL-18 indicates a role for this cytokine in myocardial remodeling.