[Prospects for the development of new prolonged forms of valproic acid derivatives for the relief of convulsive syndrome]. / Perspektivy razrabotki novykh prolongirovannykh form proizvodnykh val'proevoi kisloty dlya kupirovaniya sudorozhnogo sindroma.

Poisoning with pesticides containing convulsive substances is the cause of death of thousand people in the world. Convulsive syndrome can also develop with infection of the central nervous system, intracranial hemorrhages and strokes, alcohol withdrawal syndrome, eclampsia. Up to 10% of all of the people on the Earth had experienced seizures. The most common cause of seizures is epilepsy. Existing drugs are not always effective and have side effects. Alternative therapies are being developed. Valproates (derivatives of valproic acid) are one of the most studied drugs of choice for epilepsy and other variants of convulsive syndrome, have many years of experience in use, are included in international and Russian clinical guidelines for the treatment of epilepsy. The antiepileptic, mood stabilizing and neuroprotective properties of valproate due to pre- and postsynaptic modulation of GABA-ergic transmission, regulation of glutamate activity, serotonin and dopamine levels in the hippocampus, modulation of sodium, calcium and potassium channels, epigenetic effects on the body are described. However, valproates have a number of undesirable side effects, usually associated with high doses of drugs used for a long time. Attempts to reduce the risk through the development of drugs with controlled release of the active substance are not always effective - the high individual sensitivity of about 15% of patients with epilepsy makes standard doses toxic, the pharmacokinetics and effectiveness of the developed generics are significantly inferior to the original imported drug. An alternative could be the development of Russian preparations containing a proactive component from which valproic acid is gradually released during the metabolism.

[ISCHEMIC REPERFUSION INJURY OF HEPATOCYTES IN THE PRESERVATION OF THE LIVER TRANSPLANT].

This review is dedicated to one of the problems of liver transplantation and how to solve it. The incidence of complications after liver transplantation depends on ischemia-reperfusion injury of the graft. The global shortage of donor organs, using different technologies for conservation and graft function. This article describes the basic pathogenesis and proposed a new method for the prevention of ischemia reperfusion injury of the liver.

[Chronic hepatitis C--clinical and autonomic characteristics].

The article presents the results of a survey of 62 patients with chronic hepatitis C and 103 patients with liver cirrhosis of viral etiology. Besides clinical parameters studied autonomic features by analysis of heart rate variability at rest and active orthostasis. Indicators of frequency and spectral analysis of heart rate in study patients with chronic hepatitis C and cirrhosis of viral etiology confirmed increase in sympathetic activity and weakening of parasympathetic activity in all respects, with the sympathetic influence of enhanced active orthostasis. Indices of regulatory systems of the autonomic nervous system (stress index and the index of autonomic regulation) also indicated a statistically significant predominance sympathicotonia at rest and active orthostasis, indicating serious violations of adaptation in the examinees.

Effects of cyclophosphamide and lactulose on the release of ammonia and medium-molecular-weight substances from the intestine into blood in rats.

The effects of lactulose on the release of ammonia and medium-molecular-weight substances from the intestine into the blood and on the severity of cyclophosphamide intoxication were studied in rats. The pH and urease-dependent component of ammonia-producing activity of the cecal chyme decreased over 6 h after lactulose administration, while ammonia content in the chyme increased. Cyclophosphamide caused an increase in ammonia and, less so, glutamine level in the portal blood and in the blood collected after decapitation; this drug stimulated release of methylene blue and endogenous substances of medium-molecular-weight to the portal blood. Lactulose was virtually inessential for these changes and for the neurological status, mortality, and medium life span of rats. Hence, lactulose did not prevent cyclophosphamide-induced leakage of ammonia and medium-molecular-weight substances from the gastrointestinal tract into blood and did not reduce the severity of intoxication.