Dimerization energetics of DNA minor groove binders

The energy analysis of a dimerization in aqueous solutions of seven biologically active lexitropsins, which are different by structure, was carried out with the use of the molecular simulation method. The main stabilization of dimers was shown to take place owing to hydrophobic and intermolecular van der Waals interactions. The latter are mainly associated with energyfavorable contacts between the aromatic rings of molecules and their peptide groups. Despite the significant dipole moments of the molecules concerned, the electrostatic interactions are relatively weak and destabilize the complexes because of the unfavorable relative arrangement of molecular dipoles. Entropic factors and the dehydration were shown to also hinder the dimerizatio

НОВІ ПІДХОДИ ДО ЛІКУВАННЯ СКЛЕРОПОЛІКІСТОЗНИХ ЯЄЧНИКІВ У КЛОСТИЛБЕГІТ-РЕЗИСТЕНТНИХ ЖІНОК

At ЗО women with polycystosys ovaries ovulation was inducted by clostylbegit. Having analyzed the anamnesis, clinical and laboratory data, and the results of the induction of ovulation, we concluded, that90,1% of women are resistant to such a therapy. We need to find additional methods for inducting the ovulation in such group of patients.Проводилось исследование эфективности применения клостилбегита для индукции овуляции у женщин со склерополикистозными яичниками. В результате анализа анамнестических, клинико-лабораторных данных и оценки проведённого курса лечения ЗО женщин, пришли к выводу о резистентности женщин к этому препарату (у 90,1% случаев).Для улучшения результатов индукции овуляции необходим поиск дополнительных препаратов, которые влияют на патогенез данного заболевания.Досліджувалося використання клостилбегіту для індукціїовуляціїу жінок із склерополікістозними яєчниками. Після аналізу анамнестичних, клініко-лабораторних даних і оцінки проведеного курсу лікування ЗО жінок, зроблено висновок про резистентність жінок до даного препарату (у 90,1% випадків) і необхідність пошуку додаткових, патогенетично обґрунтованих засобів, для покращення результатів індукціїовуляції

The effect of general anaesthetics on brain lactate release

The effects of anaesthetic agents on brain energy metabolism may explain their shared neurophysiological actions but remain poorly understood. The brain lactate shuttle hypothesis proposes that lactate, provided by astrocytes, is an important neuronal energy substrate. Here we tested the hypothesis that anaesthetic agents impair the brain lactate shuttle by interfering with astrocytic glycolysis. Lactate biosensors were used to record changes in lactate release by adult rat brainstem and cortical slices in response to thiopental, propofol and etomidate. Changes in cytosolic nicotinamide adenine dinucleotide reduced (NADH) and oxidized (NAD+) ratio as a measure of glycolytic rate were recorded in cultured astrocytes. It was found that in brainstem slices thiopental, propofol and etomidate reduced lactate release by 7.4 ± 3.6% (P < 0.001), 9.7 ± 6.6% (P < 0.001) and 8.0 ± 7.8% (P = 0.04), respectively. In cortical slices, thiopental reduced lactate release by 8.2 ± 5.6% (P = 0.002) and propofol by 6.0 ± 4.5% (P = 0.009). Lactate release in cortical slices measured during the light phase (period of sleep/low activity) was ~25% lower than that measured during the dark phase (period of wakefulness) (326 ± 83 μM vs 430 ± 118 μM, n = 10; P = 0.04). Thiopental and etomidate induced proportionally similar decreases in cytosolic [NADH]:[NAD+] ratio in astrocytes, indicative of a reduction in glycolytic rate. These data suggest that anaesthetic agents inhibit astrocytic glycolysis and reduce the level of extracellular lactate in the brain. Similar reductions in brain lactate release occur during natural state of sleep, suggesting that general anaesthesia may recapitulate some of the effects of sleep on brain energy metabolism

Age-dependent effects of low-dose nicotine treatment on cocaine-induced behavioral plasticity in rats

Epidemiological evidence of early adolescent tobacco use, prior to that of marijuana and other illicit drugs, has led to the hypothesis that nicotine is a “gateway” drug that sensitizes reward pathways to the addictive effects of other psychostimulants. To test this hypothesis, we have compared the effect of a brief, low-dose nicotine pretreatment of adolescent and adult rats on subsequent locomotor response to acute and chronic cocaine. Adolescents, aged postnatal day (P) 28, and adults, aged P86, were given four daily injections of saline or nicotine (0.06&nbsp;mg/kg, i.v.). At P32 and P90, rats were given acute injections of cocaine (0, 0.4 or 1.0&nbsp;mg/kg, i.v.) and monitored for locomotor activity in either a habituated or novel test environment. To examine cocaine sensitization, rats were treated for 3&nbsp;days with saline or cocaine (0.4&nbsp;mg/kg, i.v.), and, after 1&nbsp;day of withdrawal, were given a challenge dose of cocaine (0.4&nbsp;mg/kg, i.v.). Nicotine pretreatment did not affect acute, drug-induced locomotor activity at either age. However, age differences in cocaine response were observed, with adolescent animals showing enhanced locomotor activity in the novel environment. Adolescent controls did not exhibit cocaine-induced locomotor sensitization, whereas adults did. Nicotine pretreatment during adolescence promoted the development and expression of a sensitized response to repeated cocaine exposure similar to that observed in saline-pretreated adult controls. These findings show that brief pretreatment with nicotine, in a low dose comparable to that inhaled in 2–4 cigarettes, enhances cocaine-induced behavioral plasticity in adolescent rats