Ligands with affinity to specific sequences of DNA base pairs. X. Synthesis and binding of netropsin analogs, containing a chelating copper ion peptide, with DNA

An analogue of netropsin has been synthesized consisting of two N-propylpyrrolcarboxamide units linked covalently to a copper-chelating tripeptide Gly-Gly-L-His by means of two and three glycine residues. Binding to DNA and synthetic polynucleotides of netropsin analogue containing three glycine residues between Gly-Gly-L-His tripeptide and the N-end of netropsin analogue (His-Nt) has been studied. It is shown that this netropsin analogue chelates a copper ion with 1:1 stoichiometry, similar to a free Gly-Gly-L-His peptide. It is found that this netropsin analogue occupies 3 to 4 base pairs upon binding to poly(dA).poly(dT) and poly[d(AT)].poly[d(AT)] polymers, irrespective of whether it binds in Cu(2+)-ligated or unligated forms. Binding constants and binding site sizes have been calculated for netropsin analogue complexes with DNA, poly(dA).poly(dT) and poly[d(AT)].poly[d(AT)] polymers at the [Cu2+]/[His-Nt] ratio equal to 0 and 1.0. In the three-component system including His-Nt and Cu(2+)-His-Nt, cooperative effects are recognized which can be explained by heterodimer generation on interaction of His-Nt and Cu(2+)-His-Nt at adjacent binding sites.     

Clinical computed tomographic correlations in children from a group at high risk for schizophrenia

Computed tomography (CT) was performed in 189 individuals: in 44 children of schizophrenic parents (high risk group, HRG), in 39 parents with schizophrenia or with schizophrenic disturbance, in 56 children with schizophrenia, in 50 children with consequences of early organic damages of central nervous system (mental retardation syndrome and generalized tic syndrome). The frequency of CT changes was equal in the mentioned groups but their character was quite different. The widening of brain's liquor system (89.7%), the signs of frontal and temporal atrophia (31%), foci of decreased density of cerebral brain's matter, closer in subcortical ganglia and periventricular zone, and different anomalies of brain were observed in HRG children.     

Hyperbaric oxygenation and current methods of detoxication in multimodal intensive therapy of diffuse peritonitis

The course of diffuse peritonitis has been followed up in 219 patients, 20 of these with the reactive, 165 with toxic, and 34 with the terminal stages of the condition. Multiple-modality intensive care included, besides routine therapy, local abdominal hypothermia, UV irradiation of autoblood (UVIAB), and, if indicated, hyperbaric oxygenation (HBO) and hemoperfusion. In addition to clinical tests, immunobiochemical monitoring of medium-molecular peptide fractions MM1 and MM2 and index of their distribution, as well as of circulating immune complexes CIC1 and CIC2 and the levels of immunoglobulins IgA, IgM, and IgG were the criteria for assessing the severity of intoxication and efficacy of intensive care and for predicting the course and outcome of the disease. The results indicate that HBO in combination with hemoperfusion, local abdominal hypothermia, and UVIAB have a positive impact on the clinical picture of the disease and on the time course of markers of endogenous intoxication and humoral immunity in patients with the terminal and toxic phases of diffuse peritonitis.     

The interaction of homogeneous motor conditioned reflexes during conditioned-reflex switchover: the transfer of learning and interference

The dynamics of elaboration of the conditioned switchover (CSw) of homogeneous motor conditioned reflexes (CR) with different lateralization of the motor skill was studied in rabbits. Learning of CSw was shown to pass three basic stages characterized by different degree of consolidation of the CRs, by interaction between the two CRs, and by manifestation of CSw. Stages I and II reflected the process of afferent and efferent generalization of CRs and CSw, stage III was associated with specialization of CRs and CSw. Both positive and negative transfer of motor learning as well as interference between the two motor skills took place during CSw elaboration. The highest rate of CSw acquisition was observed in rabbits displaying positive motor transfer.     

The positive effect of pretreatment with serotonin and gangliosides on the development of early mouse embryos after cryopreservation

Blood pressure (BP) during siesta declines to levels similar to those of night time sleep. The objective of the study was to assess the effect of siesta on 24-h ambulatory BP (ABP) data. Two different approaches were employed for the definition of day and night periods: (1) actual patient reported day and night intervals (ACT) with siesta period analysed as a third time period; and (2) arbitrary day and night time intervals (ARB) with the presence of siesta being ignored. A total of 203 24-h ABP recordings were analysed, with a siesta during ABP monitoring reported in 154 of them. Mean siesta BP was very close to ACT night time BP. Among recordings with a siesta, ACT daytime BP was higher and night time BP lower than the corresponding ARB BPs (P < 0.001). The magnitude of night time BP drop was greater with ACT intervals, resulting in a lower percentage of non-dippers (P < 0.001). Among 49 recordings without a siesta, differences between ACT and ARB BPs were less pronounced for daytime but not for night time. Differences in the magnitude of nocturnal BP drop between ACT and ARB periods, although statistically significant, did not affect the prevalence of non-dippers. In conclusion, analysis of 24-h BP profiles by using ARB instead of ACT day and night intervals results in underestimation of the nocturnal BP drop and overestimation of the proportion of non-dippers. This bias is more pronounced in patients who take a siesta during ABP monitoring.     

New nucleoside conjugates with phospholipids: synthesis of anti-HIV activity of rac-1-hexadecyl-2-acyl-sn-glycero-3-phosphonucleosides

New nucleoside-phospholipid conjugates were synthesized based on 1,2-disubstituted glycerides and nucleosides. These contain rac-1-hexadecyl-2-palmitoyl(or 2-methylcarbamoyl)-sn-glycero-3-phosphate as the phospholipid component and 2',3'-didehydro-3'-deoxythymidine, 1-(Z-5-hydroxypentene-2-yl)thymine, or 2',3'-isopropylideneuridine as a nucleoside component. The conjugates were synthesized by three different ways: from rac-1-hexadecyl-2-acyl-sn-glycero-3-phospodichlorides, -3-phosphatidic acids, or -3-H-phosphonates. When subjected to mild alkaline hydrolysis, conjugates containing a 2-palmitoyl group formed conjugates with the lysophospholipid component that had not yet been described. All the conjugates obtained were amorphous compounds stable at room temperature. Their hemolytic and anti-HIV activities were determined. Some conjugates were found to completely inhibit in vitro HIV-1 reproduction in lower doses than the corresponding nucleosides.     

Dynamics of lipid peroxidation and antioxidant system in patients with severe combined trauma

The objective of the study was to determine the influence of blood loss volume on lipid peroxidation (LP) process and antioxidant system (AOS) state in the patients with a heavy combined trauma. The studies were proceeded in 36 patients with a heavy combined trauma. The mean age of the patients was 40 +/- 2. A craniocerebral trauma was associated with trauma of both thorax and abdominal cavities and locomotor system. Blood loss reached 75% of circulating blood volume (CBV), mean value was 28 +/- 3%. Blood samples for the studies were obtained at admission of the patients by emergency medical service teams, and--after 4; 24 hours, 3 and 7 days after the trauma. CBV determination was made by dradioisotope method. LP and AOS state was judged from serum level of primary (conjugated dienes), secondary (malonic dialdehyde, MDA) LP products and extracellular antioxidant enzyme ceruloplasmin (CP). K coefficient, an integral indicator was used for LP-AOS system imbalance assessment. According to the obtained data, in the studied patients intensification of the LP processes manifesting in CD and MDA contents increase was most expressed from 1 to 3 days after trauma (2.0-2.6-fold, p < 0.05) and rise of TP content maximally in the 3 day 2.28-fold (p < 0.05) was observed in the there patients. At the admission of decrease (1.6-fold, p < 0.05) was registered which normalized to the 3 day. K coefficient time course study permitted to establish that as early as at the admission of the patients into the clinic its value was substantially higher than the normal one, and to the 4 hour the imbalance in the LP-AOS system increased 5.0-fold (p < 0.05). An expression of LP processes and AOS disturbances in the patients with heavy combined trauma depended on the blood loss volume. The revealed imbalance in the LP-AOS system is indicative of a necessity of inclusion antioxidants into the complex therapy.