Modern principles of the pathogenetic therapy of the burn shock

The article is devoted to the review of main directions of anti-shock therapy improvement for patients with severe burns. It is shown that the treatment efficiency can be considerably increased both by optimization of infusion volume and by the use of modern infusion drugs with anti-hypoxic and anti-oxidant effects. The use of anti-hypoxic and anti-oxidant drugs permits to change the burn shock course and to decrease its duration. Decrease in severity of tissue hypoxia, prevention of cellular membrane injury interrupt one of the circuits of burn disease pathogenesis and create the favorable conditions for realization of acute adaptation mechanisms in terms of traumatic disease conception. The modern schemes of anti-shock therapy approved at the department of thermal injuries were used in the treatment of casualties with combined burns after the armed conflict in the territory of Chechnia (1999-2001).     

Early and Long-Term Neuroendocrine Effects of Prenatal Stress in Male and Female Rats

The effects of maternal stress, termed prenatal stress (PNS) on the neuroendocrine regulation of reproduction and the stress reactivity of offspring were studied in rats. PNS prevented the formation of sexual dimorphism in catecholamine levels, aromatase activity, and androgen 5-reductase activity in the preoptic area of the brain and the mediobasal hypothalamus in 10-day-old rats. The morphological correlate of the functional lesions induced by PNS consisted of the elimination of gender-related differences in the volumes of neuron nuclei in the suprachiasmatic nucleus. Prenatal stress altered the stressand adrenergic reactivities of the hypothalamo-hypophyseal-adrenal system in mature males and females. The long-term effects of PNS were regarded as a consequence of the disruption of the hormone-neurotransmitter imprinting of the neuroendocrine system.(Director: Corresponding Member of the Ukrainian National Academy of Sciences and the Ukrainian Academy of Medical Sciences A. G. Reznikov)     

Dynamics of immune status in patients with phlegmons of the maxillofacial area during endolymphatic antibiotic therapy]

Studies of immunotropic effects of ampicillin, gentamicin sulfate, lincomycin, and rifampicin SV used in endolymphatic therapy of patients with maxillofacial phlegmons demonstrated a pronounced immunomodulating effect of rifampicin SV in polygluquine. The immunomodulating effect of lincomycin was lower, and that of ampicillin virtually null. Gentamicin sulfate suppressed some parameters of the immune status.     

Noncardiogenic pulmonary edema caused by decompression sickness: rapid resolution following hyperbaric therapy

Noncardiogenic pulmonary edema is a recognized but uncommon manifestation of type 2 decompression sickness. It typically occurs within 6 hours of a dive. Because the adult respiratory distress syndrome in this setting is believed to be due to microbubbles in the pulmonary vasculature, recompression in a hyperbaric chamber has been recommended as a form of therapy. A patient developed noncardiogenic pulmonary edema following a seawater dive to 75 feet. There was complete radiologic and clinical resolution within 5 hours of hyperbaric therapy.     

Augmentation of the sterilizing effect of neonatal androgenization with tropolone, a catechol-O-methyltransferase inhibitor, in female rats

The influence of tropolone, a catechol-O-methyltransferase (COMT) inhibitor, on the sterilizing effect of neonatal testosterone propionate (TP) has been studied in Wistar female rats. Tropolone-induced changes in COMT activity and noradrenaline (NA) and dopamine (DA) contents in the hypothalamus have been evaluated. Inhibition of COMT activity was maximal 3 h after a single injection of 0.6 mg tropolone on postnatal day 5. An increase in DA level was observed 6 h after drug injection, whereas the NA content was elevated 24 h after tropolone administration. A sexual dimorphism in hypothalamic NA content in rats was found on postnatal day 10: it was higher in males than in females. The rise of catecholamines in the hypothalamus of 10-day-old female rats induced by COMT inhibition with tropolone (0.3 mg on postnatal days 5 and 7) was unable to masculinize developing neuroendocrine regions responsible for sexual cyclicity. At the same time, combined administration of tropolone (0.1 mg daily on postnatal days 4-10) and TP (0.025 mg on day 4) enhanced the sterilizing effect of the androgen. An anovulatory sterility appeared in all experimental animals. It is suggested that a cooperative interaction occurs between catecholamines and sex steroids as determinants of brain sexual differentiation.     

Effect of a catalytic subunit of cAMP-dependent protein kinase on acetylcholine-induced chloride currents in mollusk neurons]

It is shown that the amplitude of ACh-induced chloride currents decreases with introduction of cAMP in dialyzed neurons of Helix pomatia, the rate of desensitization of the acetylcholine receptors (AChR) being insignificantly changed. Introduction of an active catalytic subunit (c.s.) of cAMP-dependent protein kinase (cAMP-PK) mimics this effect. It is supposed that the influence of cAMP on the functional properties of the AChR is mediated by the activation of cAMP-PK and further phosphorylation of the AChR by the catalytic subunits of this protein kinase.     

Anticancer prodrugs of butyric acid and formaldehyde protect against doxorubicin-induced cardiotoxicity

Formaldehyde has been previously shown to play a dominant role in promoting synergy between doxorubicin (Dox) and formaldehyde-releasing butyric acid (BA) prodrugs in killing cancer cells. In this work, we report that these prodrugs also protect neonatal rat cardiomyocytes and adult mice against toxicity elicited by Dox. In cardiomyocytes treated with Dox, the formaldehyde releasing prodrugs butyroyloxymethyl diethylphosphate (AN-7) and butyroyloxymethyl butyrate (AN-1), but not the corresponding acetaldehyde-releasing butyroyloxydiethyl phosphate (AN-88) or butyroyloxyethyl butyrate (AN-11), reduced lactate dehydrogenase leakage, prevented loss of mitochondrial membrane potential (DeltaPsim) and attenuated upregulation of the proapoptotic gene Bax. In Dox-treated mice, AN-7 but not AN-88 attenuated weight-loss and mortality, and increase in serum lactate dehydrogenase. These findings show that BA prodrugs that release formaldehyde and augment Dox anticancer activity also protect against Dox cardiotoxicity. Based on these observations, clinical applications of these prodrugs for patients treated with Dox warrant further investigation.     

The anticancer prodrugs of butyric acid AN-7 and AN-9, possess antiangiogenic properties

The antiangiogenic and antineoplastic activities of the butyric acid prodrugs AN-7 and AN-9 were demonstrated in vitro with HUVEC by inhibition of proliferation and vascular tubes formation, enhanced apoptosis, and inhibition of 22Rv-1 cells migration. In the sc implanted human prostate tumors (22Rv-1) in nude mice, AN-7 significantly inhibited Ki-67, HIF-1alpha, HER-2/neu, bFGF and increased PTEN level. AN-7 and AN-9 reduced hemoglobin accumulation in matrigel plugs implanted sc in Balb-c mice. Herein, we show that the anticancer activity of AN-7 and AN-9 can be attributed in part to their antiangiogenic activities suggesting potential therapeutic benefits for prostate cancer patients.