Quantitative ESI-MS analysis of antiarrhythmic drugs in blood plasma without chromatographic separation

A highly sensitive method for the quantitative determination of a potential antiarrhythmic drug (OF-7976) in the blood plasma has been developed. The method is based on the electron spray ionization/mass spectrometry (ESI-MS) technique without preliminary chromatographic separation and makes use of nibentan as the internal standard. A linear relationship between drug concentration and the peak intensity of ions of the analyzed substance (m/z = 398) and the internal standard (m/z = 382) is established. The detection limit is 3 ng/(0.5 ml plasma). The method is linear from 3 to 25 ng/(0.5 ml plasma) with a correlation coefficient of 0.98. The coefficient of variation was less than 7 %. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 41, No. 3, pp. 45–48, March, 2007.     

Correlations between the pharmacokinetics and dynamics of pharmacological effects of bromantane

It is shown that there is a mathematical correlation between an integral characteristic of activity of the organism (the capacity for work), electrophysiological indexes of functioning of the brain structures, and the concentration of a novel derivative of 2-aminoadamantane, bromantane, in the brain. The nature of the correlation between integral characteristics of the organism studied on different levels is found to change depending on the time elapsed from the administration of the preparation and on its concentration in the blood or target tissue. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 3 pp. 305–308, March, 1995 Presented by M. D. Mashkovskii, Member of the Russian Academy of Medical Sciences     

Na,K-Atpase in renal tissue of rats in the dynamics of experimental nephritis]

The authors undertook comparative study of the Na, K-ATPase activity in the red cells, ghost corpuscles, and in the cortex and medulla of kidneys of rats with experimental glomerulonephritis (GN) induced by injection of nephrotoxic serum (NTS), during an acute course of the process (1 and 2 weeks after NTS injection) and in chronic affection of the kidneys (10 weeks after NTS injection). The activity of the enzyme both in the red cells and in the ghost corpuscles was reduced significantly, by 28 and 22%, respectively, in the acute period of the disease (one week after NTS injection) but was restored to normal values in the period of chronic affection of the kidneys. The activity of the enzyme did not change in the cortex during the whole period of the study, but in the medulla it diminished in the acute period of the disease and remained reduced (by 27% on the average) during the chronic phase. It is concluded that reduction of the enzyme activity in the studied objects was not caused by the presence of endogenous inhibitors of the enzyme. It is suggested that reduction of Na, K-ATPase activity in the renal medulla may be one of the factors of increase of Na and water excretion in the urine in the chronic phase of GN.     

Role of Ca2+-independent phospholipase A2 and n-3 polyunsaturated fatty acid docosahexaenoic acid in prostanoid production in brain: perspectives for protection in neuroinflammation.

Various diseases of the central nervous system are characterized by induction of inflammatory events, which involve formation of prostaglandins. Production of prostaglandins is regulated by activity of phospholipases A(2) and cyclooxygenases. These enzymes release the prostaglandin precursor, the n-6 polyunsaturated fatty acid, arachidonic acid and oxidize it into prostaglandin H(2). Docosahexaenoic acid, which belongs to the n-3 class of polyunsaturated fatty acids, was shown to reduce production of prostaglandins after in vivo and in vitro administration. Nevertheless, the fact that in brain tissue cellular phospholipids naturally have a uniquely high content of docosahexaenoic acid was ignored so far in studies of prostaglandin formation in brain tissue. We consider the following possibilities: docosahexaenoic acid might attenuate production of prostaglandins by direct inhibition of cyclooxygenases. Such inhibition was found with the isolated enzyme. Another possibility, which has been already shown is reduction of expression of inducible cyclooxygenase-2. Additionally, we propose that docosahexaenoic acid could influence intracellular Ca(2+) signaling, which results in changes of activity of Ca(2+)-dependent phospholipase A(2), hence reducing the amount of arachidonic acid available for prostaglandin production. Astrocytes, the main type of glial cells in the brain control the release of arachidonic acid, docosahexaenoic acid and the formation of prostaglandins. Our recently obtained data revealed that the release of arachidonic and docosahexaenoic acids in astrocytes is controlled by different isoforms of phospholipase A(2), i.e. Ca(2+)-dependent phospholipase A(2) and Ca(2+)-independent phospholipase A(2), respectively. Moreover, the release of arachidonic and docosahexaenoic acids is differently regulated through Ca(2+)- and cAMP-dependent signal transduction pathways. Based on analysis of the current literature and our own data we put forward the hypothesis that Ca(2+)-independent phospholipase A(2) and docosahexaenoic acid are promising targets for treatment of inflammatory related disorders in brain. We suggest that Ca(2+)-independent phospholipase A(2) and docosahexaenoic acid might be crucially involved in brain-specific regulation of prostaglandins.     

Distribution of thietazole in organs and tissues of rats after single and repeated administration

We studied the kinetics of thietazole distribution in the liver, brain, kidneys, spleen, heart, skeletal muscles, lungs, adipose tissue, and testicles after single and repeated administration of this drug. Single and repeated administration of thietazole was followed by elimination of this drug from the blood into organs and tissues. After repeated administration, thietazole was selectively accumulated in the spleen. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 5, pp. 555–557, May, 2008     

Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations.      

The methods of traditional medicine in outpatient polyclinic practice

Some 7950 patients have been treated at the traditional medicine department of the Consulting and Diagnostic Center N52, 2/3rds of them came after long and unsuccessful medicamental treatment. Psychotherapy, manual therapy and acupuncture-reflex methods were successful in 86-93% of cases. They are recommended for local clinics provided that the latter are properly equipped and stuffed.