From Toxicity to Selectivity: Coculture of the Fluorescent Tumor and Non-Tumor Lung Cells and High-Throughput Screening of Anticancer Compounds.

For the search of anticancer compounds in modern large chemical libraries, new approaches are of great importance. Cocultivation of the cells of tumor and non-tumor etiology may reveal specific action of chemicals on cancer cells and also take into account some effects of the tumor cell's microenvironment. The fluorescent cell cocultivation test (FCCT) has been developed for screening of substances that are selectively cytotoxic on cancerous cells. It is based on the mixed culture of lung carcinoma cells A549'_EGFP and noncancerous fibroblasts of lung VA13_Kat, expressing different fluorescent proteins. Analysis of the cells was performed with the high-resolution scanner to increase the detection rate. The combination of cocultivation of cells with scanning of fluorescence reduces the experimental protocol to three steps: cells seeding, addition of the substance, and signal detection. The FCCT analysis does not disturb the cells and is compatible with other cell-targeted assays. The suggested method has been adapted for a high-throughput format and applied for screening of 2,491 compounds. Three compounds were revealed to be reproducibly selective in the FCCT although they were invisible in cytotoxicity tests in individual lines. Six structurally diverse indole, coumarin, sulfonylthiazol, and rifampicin derivatives were found and confirmed with an independent assay (MTT) to be selectively cytotoxic to cancer cells in the studied model.

[Criteria of decision on the access for laparoscopic choledocholithotomy].

The article presents an experience with operative treatment of 187 patients for choledocholithiasis using endovideosurgical technology. The conditions influencing the optimal choice of places for introduction of trocars responsible for maximal efficiency of the intervention were analyzed. Principal criteria of the operative access were established: the depth of operative procedure, distance between the xiphoid process and the place of introduction of the epigastral trocar, the angle of operative procedure, the angle of ascent.

[15-year experience of using relaparoscopy in the diagnostics and treatment of complications after laparoscopic choledoholithotripsy].

Results of relaparoscopy were analyzed in 42 patients with complications appearing after using 297 laparoscopic choledocholithotomies. Relaparotomies were classified according to the indications and terms from the main interventions. An analysis of complications after laparoscopic choledocholithotomy was made. The authors made a conclusion that relaparoscopy was an effective little-invasive method of diagnostics and correction of postoperative complications.

[Dynamics of immunological and clinical parameters in the treatment of childhood schizophrenia].

A state of innate and adaptive immunity (leukocyte elastase (LE) activity, alpha(1)-proteinase inhibitor (alpha(1)-PI), the level of autoantibodies to nerve growth factor (Aab-NGF) and to basic myelin protein), have been studied in the blood serum of children with schizophrenia and compared to the changes of their clinical-psychopathological state. It has been shown that the exacerbation of schizophrenic process with early onset is accompanied by the activation of some parameters of innate immunity. But the higher activity of LE and alpha(1)-PI before the treatment cannot be considered as a predictive marker of therapeutic efficacy. At the same time, the decrease of LE activity during the treatment is a significant predictor of favorable therapeutic response. The unchanged level of Aab-NGF comparing to controls is also a favorable factor associated with therapeutic efficacy.

[Depressive states in early childhood].

A group of 75 children of early age with depressive states of different origin comprising 25 children at high risk for schizophrenia, 30 orphans and 20 children with consequences of perinatal encephalopathy were examined. Clinical symptoms of these disorders had a number of peculiarities caused by depression origin, risk factors and the age. The most common features are the presence of somatic depression masks, somato-autonomic disturbances and signs of mental and physical retardation.

[A state of innate and adaptive immunity in children with schizophrenia and in the high-risk group for the disease].

Leukocyte elastase (LE) activity, alpha1-proteinase inhibitor (alpha1-PI), C-reactive protein (CRP) as the indices of innate immunity and the level of autoantibodies to nerve growth factor (Aab-NGF) and to basic myelin protein (Aab-BMP) as the indices of adaptive immunity have been studied in the blood serum of 40 children at high risk for schizophrenia and in 32 children with schizophrenia. In the high-risk group, an increase both of the LE activity, CRP content and variance of alpha1-PI concentrations, indicating the activation of innate immunity, was found. LE activity correlated with severity of schizotypal diathesis. The development of schizophrenic process is accompanied by generalization of the immune response: along with activation of the innate immunity, there was activation of immunity acquired as an increase of the level of autoantibodies to neuroantigenes. It is suggested that activation of innate and adaptive immunity is related to the processes determining the disturbances of the nervous system development.

[Nerve growth factor auto-antibodies in children with various forms of mental dysontogenesis and in schizophrenia high risk group]. / Autoantitela k faktoru rosta nervov u detei s razlichnymi formami psikhicheskogo dizontogeneza i iz gruppy vysokogo riska po shizofrenii.

The level of autoantibodies (AAb) to nerve growth factor was evaluated in blood serum of 163 children with different forms of mental dysontogenesis of endogenic, residual-organic, psychogenic and deprivative origin. Significant elevation of the level of AAb was found in all forms of psychic dysontogenesis. The most significant elevation of the level of AAb (p < 0.01), as compared with the controls (45 children), was characteristic for endogenic forms of dysontogenesis (schizophrenia, early children's autism, schizotypic diathesis). The level of AAb was also found as an indicator of the acuteness of the pathologic state. Besides, its elevation was observed 1-2 weeks prior to the onset of the clinical exacerbation. Elevation of AAb level was also found in psychic dysontogenesis of residual-organic nature (children with perinatal encephalopathy), but it was not so significant as compared with the controls (p < 0.05%). The analysis in the age dynamics of children from this group revealed, that AAb level may serve as some prognostic index of the severity of psychic dysontogenesis. The level of AAb differs some states in schizotypic diathesis and deprivative dysontogenesis, which are clinically quite similar. The method for the estimation of serum AAb level may be proposed as screening in prophylactic medical examination of children from the first year of life under conditions of pediatric outpatient service for identification of risk-groups by psychic dysontogenesis to perform early special psychoprophylaxis.

[Electroencephalographic correlates of schizophrenic type mental disorders at an early age in childhood]. / Elektroéntsefalograficheskie korreliaty psikhicheskikh narushenii shizofrenicheskogo spektra v rannem detskov vozraste.

Electroencephalographic study was performed in 30 children of 1-3 years old from the group with the high risk of schizophrenia. Clinical observation of the patients was performed in the period of EEG recording and follow-up study was also made during 10-12 years. Three groups of patients were picked out with the differences in both clinical and electrophysiologic indices. Bundle beta-activity was registered on EEG in the cases of an active schizophrenic process. A presence of the spindles of the sleep and their dominance on EEG were characteristic for children with nonprocessual disorders of psychopathic-like type with disinhibition of the drives. Hypersynchronism of delta- and theta-activities were observed in the cases of schizotypic diathesis and an early children's autism with the predominance of paroxysmal somato-autonomic disorders.

[Nerve growth factor auto-antibodies in the sera of mothers of schizophrenic children and children from high risk group]. / Autoantitela r faktory rosta vervov v syvorotke krovi materei bol'nykh shizofreniiei detei and detei gruppy vysokogo riska.

A level of autoantibodies (aAB) to nerve growth factor (NGF) was measured in blood serum of children from 4 groups: 1) schizophrenic patients; 2) children from the families, in which one of the parents suffered with schizophrenia (high risk groups of schizophrenia); 3) children with residual-organic damages of CNS; 4) control group. This index was also determined in their mothers. Significant elevation of a titer of aAB to NGF was observed in blood of children from groups 1 and 2 as well as in their mothers, as compared with 3 and 4 groups. Among the mothers of the children from 1 and 2 groups there were met women with different endogenous mental disorders, with the disorders of personality as well as mentally healthy women. An increase of a level of aAB to NGF was found in all the women from groups 1 and 2, independently of their mental status including mentally healthy women. Such results allow to consider elevated level of aAB to NGF as a risk factor of mental pathology.

[Depressive states at an early age]. / Depressivnye sostoianiia v rannem vozraste.

100 children of 1-3 years old were observed. In 50 of them depressive states developed in conditions of total deprivation--the situation of orphanhood. In other 50 children the depressions were caused by partial deprivation--upbringing by schizophrenic mother (children from group with high risk of schizophrenia). Three variations of depression were found in the first group: autonomic, somatizated, and regressive-apathetic. Depressions in the second group were presented either by infantile depression or by infantile distress-syndrome in frames of schizotypic diathesis.

[Clinical characteristics and typology of the obsessive-compulsive disorder in slowly-progressing recurrent schizophrenia with the onset in childhood and adolescence]. / Klinicheskie osobennosti i tipologiia sindroma naviazchivostei pri maloprogredientnoi pristupoobraznoi shizofrenii s debiutom v detskom i podrostkovom vozraste.

As many as 56 patients suffering from slow-progredient attack-like schizophrenia running its course with the predominance of obsessions in the clinical picture were examined and followed up for 3 to 5 years. At the moment of the examination the patients' age ranged from 8 to 15 years. It has been established that during slow-progredient attack-like schizophrenia in children and adolescents, obsessions occur in the structure of "large" obsessive syndromes characterized by polymorphism of psychopathological disorders and always including remarkable affective symptomatology. Six types of obsessive conditions were distinguished, each of which was marked by a definite stereotype of the disease natural history and correlated with the degree of the process progress. Among the types of obsessive conditions described, depressive ones with obsessions (three types) led on the whole to less pronounced alterations of the personality than obsessive-anxious ones, particularly anxious-hypochondriac attacks after the completion of which there formed relatively more profound personality changes.