Expression of vitamin D receptors in the superior cervical ganglia of rats.

We investigated the role of vitamin D in the sympathetic nervous system including the distribution of vitamin D receptors (VDR), 1α-hydroxylase and 24-hydroxylase (CYP24) in neuronal subpopulations and satellite glia in the superior cervical ganglia (SCGs) of rats using immunohistochemistry. VDR immunoreactivity was observed in the cytoplasm and nucleus of nearly all neurons in the SCG. Intensity of VDR fluorescence was significantly greater in the cytoplasm of neuropeptide Y (NPY) negative somata compared to NPY positive neurons. Immunoreactivity for 1α-hydroxylase also was observed in the cytoplasm of all neurons of the SCG, but the intensity of fluorescence was less in the nuclei. To the contrary, the immunoreactivity for CYP24 was stronger in the nuclei, although it was present at lower intensity also in the cytoplasm of neurons. VDR and 1α-hydroxylase immunofluorescence was observed in many non-neuron cells, except satellite glial cells, which exhibited weak CYP24 immunofluorescence. Expression of VDRs and key metabolizing enzymes indicated the importance of vitamin D in the autonomic nervous system and the ability of sympathetic neurons to activate and deactivate vitamin D for its autocrine and paracrine roles.

Nuclease stability as dominant factor in the antiviral activity of oligonucleotides directed against HSV-1 IE110.

The anti-herpes simplex virus type 1 (anti-HSV-1) efficacy of a series of oligonucleotides was determined as a function of their chemical structure. All oligonucleotides consisted of the same sequence directed against the translation initiation codon of the HSV-1 immediate early gene. The oligonucleotides were modified with phosphorothioate linkage patterns according to various protection strategies against nucleolytic degradation. We show that nuclease resistance is the dominant factor that determines the antiviral efficacy in this series. A minimal protection strategy, consisting of end-capping and pyrimidine protection, has proven to be particularly useful, because it not only yields nuclease-resistant oligonucleotides but also minimizes non-sequence-specific effects.

Secondary metabolites by chemical screening. 7. I. Elaiophylin derivatives and their biological activities.

The synthesis and the biological activity of 34 acyl derivatives of elaiophylin (1) and 6 deglycosidation products were described. Especially the unsymmetric deglycosidation products 33, 38 and 40 and dimethyloctahydroelaiophylin (21) exhibited an activity against nematodes.

[The influence of cardiogreen on the albumin binding of bilirubin in the neonatal period]. / Uber den Einflubeta des Cardiogreens auf die Albuminbindung des Bilirubins in der Neonatalperiode

The albumin-binding of bilirubin may be disturbed by pharmacologically inert substances. This is true for Cardiogreen as used for dye dilution curves. The displacement of bilirubin from its albumin-bindung, examined in vitro by Sephadex filtration, is stronger for Cardiogreen than for Gantrisin known to cause kernicterus even in mild hyperbilirubinemia. However, from differences in dosage and the pharmacokinetics of the two substances it may be concluded, that the risk of possibly causing a kernicterus by Cardiogreen is limited to only extrem cases.

[Cell electrophoretical characterization of the surface of Candida guilliermondii]. / Zellelektrophoretische Charakterisierung der Oberfläche von Candida guilliermondii.

The electrical properties of the outer layer of the cell wall of a hydrocarbon-grown yeast C. guilliermondii were studied in detail by cell electrophoresis. Some experiments were also made with the yeast S. cerevisiae. The mobilities of the yeasts were measured as a function of pH at pH 2-11.5 and constant ionic strength I = 0.02 mol/l. For identification of surface groups the pH-mobility curves are used to calculate pK-values. The results indicate the presence of amino and carboxyl groups on the surface of C. guilliermondii. These groups are probably a part of a glyco-protein with an isoelectric point at pH 3.3 located on the surface. Electrophoresis of droplets of mineral oil coated with adsorbed protein layer confirms these conclusions. The importance of this glycoprotein in hydrocarbon uptake is discussed.

V. Exercise studies in children with congenital heart disease. An earpiece densitometric investigation.

Twenty-three patients have been studied by exercise testing during right heart catheterization. Cardiac output was measured by the earpiece densitometric technique before, during and after the exercise period. It is concluded that the earpiece densitometric technique in conjunction with exercise testing offers an attractive alternative for the study of pressure and flow characteristics in children with congenital heart disease.

II. Cardiac output studies in infants and children undergoing right heart catheterization.

Cardiac output figures from 97 patients were computed by earpiece densitometry and correlated to various dimensional parameters. Stroke volume was better correlated to body dimensions than cardiac output indicating that patients undergoing right heart catheterization were not in basal state.

IV. Evaluation of dichromatic earpiece densitometry in children with left-to-right shunts.

Earpiece densitometry was performed in 60 infants and children with left-to-right cardiovascular shunts. The method was found to possess a high diagnostic sensitivity with respect to identification of the left-to-right shunt. Earpiece densitometry was in this respect clearly superior to conventional method using oxygen saturation figures. Quantitation of pulmonary blood flow by both densitiometric and oxygen content technique in a small number of patients indicates that the dye dilution technique gives values somewhat in excess of the Fick method. It is concluded that quantitation of the magnitude of the left-to-right shunt and pulmonary blood flow is disturbed by the fact that indicator material is recirculated before the ascending limb of the primary curve is fully inscribed.

Inhibition of viral growth by antisense oligonucleotides directed against the IE110 and the UL30 mRNA of herpes simplex virus type-1.

In the present work we elucidate that the identification of active sequences for a given target is one of the principle hurdles of antisense oligonucleotide therapeutics. A number of 100 oligonucleotides directed against different target genes of HSV-1 and different locations within those genes were screened for antiviral activity. To facilitate comparison, the same length and the same chemical modification were used for all oligonucleotides: 20mers with two phosphorothioate linkages at both the 5'- and the 3'-end. No sequence-independent effects were observed with this type of modification. Surprisingly, only six oligonucleotides did show significant antiviral activity, the most active one (#6) being directed against the translation initiation site of IE 110.

I. Validity of dichnomatic earpiece densitometry for quantitative studies in children with shunt-free cardiovascular malformations.

Cardiac output was assessed in 16 children without evidence of cardiovascular shunts from simultaneously recorded earpiece and cuvette densitometric tracings. The earpiece set-up was calibrated by the end-tail method. Both instruments gave linear response to dye concentrations used. There was a close correlation between cardiac output figures recorded by the two methods (r equal to 0.95) and no systematic difference occurred. It is concluded that in infants and children earpiece densitometry constitutes a rapid and accurate method for quantitative circulatory studies.

Acid-base and electrolyte balance in infants of diabetic mothers. Vaginal delivery versus caesarean section.

The acid-base and electrolyte balance of 30 women studied at delivery and in their infants during the first 48 h. 18 women were diabetics, 10 of these were delivered vaginally (DMvag) and 8 by elective caesarean section (DMcs). 12 healthy women were vaginally delivered (HMvag). The infants of diabetic mothers (IDM) received active infusion therapy. At birth the DMvag and their infants (IDMvag) had a more pronounced metabolic acidosis than the DMcs and their babies (IDMcs). The largest metabolic acidosis occurred, however, in the group of HMvag and their infants (IHMvag). After birth no significant differences were obtained in the acid-base and electrolyte balance between IDMvag and IDMcs. The plasma potassium level remained lower in IDM than in IHM. The study stress the importance of adequate management of diabetes in pregnancy in combination with active intravenous therapy during delivery and to the infant in the immediate neonatal period. The slightly larger metabolic acidosis seen in combination with vaginal delivery suggests that this mode of delivery should not be attempted uncritically in diabetic women.

Synthesis and binding properties of oligodeoxynucleotides containing phenylphosphon(othio)ate linkages.

A method for the synthesis of chimeric oligodeoxynucleotides comprised of phosphodiester and phenylphosphonate [3'-O-P(= O)(C6H5)-O-5'] or phenylphosphono-thioate [3'-O-P(= S)(C6H5)-O-5'] linkages has been developed. Synthesis was performed using suitably protected nucleoside phenylphosphonamidites as building blocks following an adjusted solid-phase phosphoramidite synthesis protocol. The new oligodeoxy-nucleotide analogues were characterized by electrospray ionization- and matrix-assisted laser desorption mass spectrometry, as well as by 31P NMR spectroscopy. Additionally, their binding properties to complementary oligodeoxynucleotides has been studied.