Evaluation of the clinical safety of gadodiamide injection, a new nonionic MRI contrast medium for the central nervous system: a European perspective.

Gadodiamide injection is a new nonionic paramagnetic, extracellular contrast medium. Its safety at a dose of 0.1 mmol/kg body weight was evaluated in a large European multicentre trial on adults referred for contrast-enhanced MRI of the central nervous system.

[Clinical evaluation of the tolerability of gadodiamide, a new nonionic contrast agent in MRI of the central nervous system].

Gadodiamide injection (Gd-DTPA-BMA) is a new non-ionic paramagnetic contrast agent for which the safety at the dose 0.1 mmol/kg was evaluated during a European multicentre study on a large population of adult patients who had an MR examination of the central nervous system with contrast medium. The safety analysis was performed on 2,102 patients by recording the adverse events observed during injection and up to 24 hours after the injection.

A method for determining the relative effect of ligands on A-T and G-C base pairs in DNA: applications to metal ions, protons and two amino acids.

A new method is described for the study of specific interactions of low-molecular ligands with the base pairs of DNA. This method is based on the comparative analysis of melting temperature changes in DNAs of different GC-content in the presence of low molecular weight ligands. In this paper, the method is applied to Mn2+, Ni2+, Co2+ ions, deprotonation, amino acids, beta-alanine and gamma-aminobutyric acid (gamma-ABA).

[Selective effect of ionization of nitrogen bases on the thermostability of AT- and GC-pairs of DNA].

The ionization specific influence of nitrogen bases on thermostability of AT- and GC-pairs of DNA has been investigated by the method of DNAs melting temperature analysis. It has been shown that the change of temperature interval of DNA helix-coil transition when changing pH environment is due to specific ionization of AT- and GC-pairs of nitrogen bases.

Differences in the central hypotensive actions of alpha-methyldopa and clonidine in the spontaneously hypertensive rat: contribution of neurons arising from the B3 and the C1 areas of the rostral ventrolateral medulla.

The rostral ventrolateral medulla (RVLM) is the proposed site of origin of bulbospinal excitatory vasomotor neurons, and this brainstem area gives rise to chemically distinct populations of neurons, including serotonin-containing neurons of the B3 group and epinephrine-containing neurons of the C1 group, which independently serve sympathoexcitatory functions. In the present study, we sought to establish (a) whether distinct and chemically specific pathways originating in the C1 or B3 regions are involved in the antihypertensive effects of alpha-methyldopa (methyldopa) and clonidine and (b) if so, whether these effects are related to an activation of alpha-adrenoceptors in these areas. Microinjections of methyldopa (6 nmol) or clonidine (5 nmol) were made in the C1 or B3 area in intact spontaneously hypertensive rats (SHR), pretreated with 5,7-dihydroxytryptamine (5,7-DHT) or with phentolamine.

Changes in serotonin metabolism in the rat raphe magnus and cardiovascular modifications following systemic administration of clonidine and other central alpha 2-agonists: an in vivo voltammetry study.

By using the in vivo voltammetry, it was demonstrated that an injection of clonidine induced both cardiovascular modifications (hypotension and bradycardia) and a decrease in the level of 5-hydroxyindolacetic acid (5-HIAA) in the ventromedial B3 serotonergic (5-HT) cell bodies of the medulla oblongata of the rat. The cardiovascular effects of clonidine and of two other imidazolic compounds (detomidine and medetomidine) are likely to be related to their alpha 2 adrenoceptor agonist properties since hypotension and bradycardia were completely antagonized by idazoxan. The decrease in levels of 5-HIAA, induced by these three imidazolic compounds is likely to represent the combination of two additional mechanisms: (i) the stimulation of the alpha 2 adrenoceptors which could contribute to 55% of the decrease observed for the extracellular 5-HIAA and (ii) the interaction with a non-alpha 2 site (through a putative imidazole recognition site), corresponding to the part of the decrease (about 45%) which was not prevented by idazoxan.

[DNA helix-coil transition in alkaline medium].

Dna helix-coil transition in th alkaline medium was considered theoretically and experimentally. On the basis of the theory and experimental comparison the DNA double-stranded form deprotonation was revealed.

[Effect of aflatoxin B1 on DNA enzymatic methylation and secondary structures of the rat liver].

Methylation and secondary structure of DNA in rat liver versus time of aflatoxin B1 (AfB1) treatment were studied. A 50% drop in 5-methylcytosine level in liver DNA as compared with control was observed long before tumor development. Also, certain changes in DNA secondary structure were seen.

[Selective effect of ligands on AT- and GC-pairs of DNA bases].

A method is proposed for investigating the specific influence of ligands on DNA AT- and GC-pairs based on the comparison of the width of transition temperature interval of DNA with a strongly pronounced block-structure and dependence of the control DNA melting temperature on their GC-content. Such a comparison allows to define separately the contribution of nonspecific effects causing a change of the width of transition temperature interval. The method is used for studying the specific influence of beta-alanine and nu-aminobutyric acid on AT- and GC-pairs.

In vivo voltammetry in the B3 group of serotonin neurons of the rat medulla oblongata after drug-induced modifications of arterial pressure.

Differential normal pulse voltammetry (DNPV) using an electrochemically treated carbon fiber electrode was applied to the investigation of the in vivo changes in extracellular 5-hydroxyindoleacetic acid (5HIAA) in the B3 group of serotonin neurons during experimental manipulations of arterial pressure. Drug-induced hypertension (phenylephrine infusion) caused, during the infusion, an increase in extracellular 5HIAA concentration which continued to rise, reaching +100% 2 hours after stopping the infusion. In contrast, drug-induced hypotension (sodium nitroprusside infusion) was not associated with any change in extracellular 5HIAA during the infusion while the return to the initial arterial pressure caused a progressive increase in the electrochemical signal, reaching +50% one hour after stopping the infusion.

[Changes in the structure of DNA induced by sarcolysine in vivo and in vitro].

Secondary structure and the rate of methylation of DNA, isolated from normal and malignant liver tissues (sarcoma 45) were studied in vivo and in vitro in presence of sarcolysine. The differential melting curve (DMC) in the DNA from malignant tissue was shifted, compared with that of the liver DNA, to the low temperature side and was characterized by appearance of an additional peak in the region of 50-60 degrees. A considerable increase in the level of methylation has been also noted in the DNA from malignant tissue.

[DNA conformation and thermostability of aqueous solutions of beta-alanine and gamma-aminobutyric acid].

It has been shown that at low concentrations of rare amino acids (from 10(-3) M to 10(-1) M of the substance) stechiometric complexes amino acid -- DNA are formed, which bring about partial substitution of counterions screening phosphate groups and to a change of spatial structure of DNA water molecules. The DNA-solvent molecular interactions are changed, accompanied by an abrupt decrease of helix-coil enthalpy transition which leads to the unwinding of DNA double helix. In the region of amino acid high concentrations (greater than 1-1,5 M) a rise of thermostability and winding of DNA double helix is observed.

[DNA conformation and thermostability in urea aqueous solutions].

It is suggested from the character of the change of circular dichroism spectra that in the presence of urea winding of DNA double helix takes place within the bounds of B-family of forms. It is shown that the realized conformation of DNA differs from the experimentally known forms of DNA belonging to B-family. Urea destabilizes the DNA molecules without connection with helical and melt pairs of DNA nitrous bases.