[The relationship of cytochrome P450 isoforms with the efficacy and safety of antipsychotic and antidepressant therapy]. / Svyaz' izoform tsitokhroma P450 s effektivnost'yu i bezopasnost'yu terapii antipsikhotikami i antidepressantami.

Cytochrome P450 (CYP450) is the leading enzyme in the biotransformation of most psychotropic drugs. CYP450 gene polymorphisms determine a patient's endophenotype with respect to the activity of enzymes of the family and affect the metabolism of prescribed antipsychotics and antidepressants. Categorizing patients by endophenotype during genotyping is likely to help simplify the selection of therapy in clinical practice. Co-prescribing drugs that may be inhibitors or inducers of CYP450 isoforms, in turn, may lead to adverse reactions or no effect of therapy. The article presents a compilation of known pharmacogenetic recommendations regarding the four major endophenotypes of metabolizers.

[Primary amyloidoma of the brain]. / Pervichnaya amiloidoma golovnogo mozga.

Primary brain amyloidoma is rare tumor-like lesion characterized by focal accumulation of insoluble fibrillar aggregates of amyloid in brain tissue without systemic amyloidosis. Literature review and a case report of primary brain amyloidoma in 61 years old female are given with a special attention on the complexity of preoperative diagnosis.

Social and Cognitive Impairments in Rat Offspring after Ultrasound-Induced Prenatal Stress.

We studied the possibility of developing an autism model based on chronic prenatal psychological stress caused by variable frequency ultrasound 20-45 kHz. The offspring of female rats stressed during pregnancy demonstrated reduced time of social contacts in the social interaction test, increased anxiety in the open-field test, and memory impairment in the Morris water maze test in comparison with the control (intact) rat offspring. We also found a reducing trend in the BDNF gene expression in the amygdala in males of the experimental group. The results showed the possibility of developing the animal autism model based on prenatal stress.

[Primary splenic angiosarcoma]. / Pervichnaia angiosarkoma selezenki.

Primary splenic angiosarcoma is a rare and high-grade vascular tumor having a significant metastatic potential. The authors give the data available in the literature and describe their own case of primary splenic angiosarcoma in a 42-year-old male patient with multiple distant metastases in the lymph nodes and skin. The paper shows some difficulties in the morphologic diagnosis of this tumor.

[Morphological features of IgG4-related lesions at various sites]. / Morfologicheskie osobennosti IgG4-sviazannykh porazhenii razlichnykh lokalizatsii.

OBJECTIVE: To determine the morphological features of IgG4-related lesions and to improve pathomorphological criteria for diagnosing various clinical variants of IgG4-related disease. MATERIAL AND METHODS: Biopsy and surgical materials from 100 patients with tumor-like lesions at various sites (63 cases of IgG4-related lesion and 37 cases of non-IgG4-related inflammatory processes) were studied. Histological and immunohistochemical studies were conducted to determine the absolute counts of CD138+ cells, IgG+ and IgG4+ in the inflammatory infiltrates, as well as IgG4/IgG and IgG4/CD138 cell ratios. RESULTS: When IgG4-related disease manifested, pancreatic, lacrimal, and salivary gland lesions prevailed. Brisk lymphoplasmacytic infiltration is characteristic for tissue damage in the eye, salivary glands, thyroid, pancreas, and skin. The formation of moiré fibrosis was specific to damages to the pancreas, liver and bile ducts, and eye tissues. Obliterative phlebitis is most often observed in pancreatic and salivary gland lesions. According to international criteria, the frequency of achieving the required level of IgG4+ plasma cells in each organ was high in lesions of the pancreas, bile ducts, and lymph nodes and that was low in lesions of the salivary and lacrimal glands and skin. The IgG4+/CD138+ and IgG4+/IgG+ cell ratios exceeded 40% in all cases. CONCLUSION: The morphologic diagnosis of IgG4-related disease is based on the detection of lymphoplasmacytic infiltration, moiré fibrosis, and obliterative phlebitis, as well as on the calculation of the absolute number of IgG4+ plasma cells in the inflammatory infiltrate and on the determination of IgG4+/IgG+ and IgG4+/CD138+ cell ratios. The number of IgG4+ plasma cells depends on the location of the lesion and on the phase of the process.

[Gastric cancer concurrent with IgG4-related disease: A clinical case and a review of literature]. / Sochetanie raka zheludka s IgG4-svyazannoi bolezn'yu (klinicheskoe nablyudenie i obzor literatury).

The paper presents the data available in the literature on IgG4-related disease (IgG4-RD) concurrent with malignancies at different sites, as well as possible common pathogenetic mechanisms of their development and morphological diagnostic criteria for IgG4-RD. The authors give their own observation of gastric signet ring cell carcinoma concurrent with morphologically verified IgG4-RD.

[FACTORS AFFECTING SPERMATOGENESIS PRESERVATION IN RATS WITH SEMINIFEROUS TRACT OBSTRUCTION].

The aim of the study was to examine the effect of the seminal tract obstruction of different degree and duration on the morphological and functional condition of testicular tissue. The study was conducted in 50 male Wistar rats. Three experimental models of seminiferous tract obstruction were set up: obstruction of the proximal part of the ductus deferens, obstruction of the distal part of the ductus deferens and obstruction of at the epididymis level. Morphological evaluation of testicular tissue was performed at 3 and 6 months after the obstruction. It was found that obstruction at the epididymis level caused the most severe impairment of spermatogenesis.

Caspase expression in placental terminal villi in spontaneous and induced pregnancy.

Placental levels of caspase 1, 8, and 10 were studied by the immunohistochemical method in full-term spontaneous and induced pregnancies. The levels of these caspases in the placental terminal villi were significantly higher in induced pregnancy. The changes were more marked after intracytoplasmatic injection of spermatozoa.

Expression of insulin-like growth factors in the placenta in preeclampsia.

Comparative morphological study of the placentas in women with preeclampsia and small-for-date fetuses was carried out. Expression of insulin-like growth factor-1 (IGF-1), insulin-like growth factor-2 (IGF-2), and insulin-like growth factor binding protein-3 (IGFBP-3) was detected by immunohistochemical methods. Low expression of IGF-1 and high expression of IGF-2 and IGFBP-3 in the placental tissue depending on preeclampsia severity were detected. The most pronounced changes were found in preeclampsia associated with small-for-date fetuses.

[Comparative immunohistochemical evaluation of vascular endothelial growth factor and its receptors in the placental villi in gestational diabetes mellitus and type 1 diabetes].

The authors performed a comparative immunohistochemical study of placental vascular endothelial growth factor (VEGF) and its receptors (VEGFR-1, VEGFR-2 and VEGFR-3) in gestational diabetes mellitus and type 1 diabetes. The expression of VEGF and its receptors was ascertained to be increased in the placental terminal and stem villi, mostly in type 1 diabetes. The changes found in the immunophenotype of terminal and stem villi suggest that the placenta is damaged and this may accordingly lead to intrauterine growth disturbances in the fetus and further to diseases in the neonatal infant.

The expression of matrix metalloproteinases in placental tissue depends on the severity of undifferentiated connective tissue dysplasia.

Immunohistochemical study of MMP-2 and MMP-9 expression in placental tissue of pregnant patients with undifferentiated connective tissue dysplasia of different severity showed that more severe condition was associated with higher expression of these MMP, this underlying the development of pregnancy and labor complications. The most pronounced elevation of the studied MMP levels was found in the basal plate decidual cells in women with undifferentiated connective tissue dysplasia of more than 18 score.

[Early neonatal mortality in the Russian Federation in 2010].

The paper analyzes the data of the Federal State Statistics Service on early neonatal mortality in the Russian Federation as a whole and its federal districts in 2010. There was a steady decline (ranging from 6.52 to 2.75%) in the mean early neonatal mortality rates in the Russian Federation in 2000-2010. In 2010, there were low, moderate, and high early neonatal mortality rates in 59 (71.1%), 20 (24.1%), 4 (4.8%) federal subjects, respectively. Most neonatal deaths were noted within the first 24 hours of life. According to the Federal State Statistics Service data, the commonest cause of early neonatal death in Russia is respiratory distress (103.2 deaths per 100,000 live births), hyaline membrane disease in particular. Among the causes of neonatal death, maternal diseases unrelated to pregnancy are indicated most commonly (in 22.7% of cases).

[Stillbirth rates in the subjects of the Russian Federation in 2010].

The paper analyzes the 2010 Russian State Statistics Service data on stillbirth rates in the Russian Federation and its subjects. There was a steady decline in the mean stillbirth rate (from 6.8 to 4.67 per thousand) in the Russian Federation in 2000-2010. In 2010, the rate was low in 10 (12%) subjects, moderate in 42 (50.6%), and high in 31 (37.4%). The reduction in the proportion of intranatal stillbirth is naturally accompanied by the increase in its antenatal component. According to the data of the Russian State Statistics Service, the most common cause of stillbirth is intrauterine hypoxia and birth asphyxia: 391.9 per 100,000 born alive and dead. The most frequent maternal cause was notified to be placental pathology: 209 per 100,000 born alive and dead.

[Development of a diagnostic test system for early non-invasive detection of prostate cancer based on PCA3 mRNA levels in urine sediment using quantitative reverse tanscription polymerase chain reaction (qRT-PCR)].

The wide introduction of prostatic specific antigen (PSA) determination into clinical practice has resulted in a larger number of prostate biopsies, while the lower age threshold for PSA has led to a larger number of unnecessary prostate biopsies. Hence, there is a need for new biomarkers that can detect prostate cancer. PCA3 is a noncoding messenger ribonucleic acid (mRNA) that is expressed exclusively in prostate cells. The aim of the study has been to develop a diagnostic test system for early non-invasive detection of prostate cancer based on PCA3 mRNA levels in urine sediment using quantitative reverse transcription polymerase chain reaction (qRT-PCR). As part of the study, a laboratory diagnostic test system prototype has been designed, an application methodology has been developed and specificity and sensitivity data of the method has been assessed. The diagnostic system has demonstrated its ability to detect significantly elevated levels of PCA 3/KLK 3 in samples from prostate cancer (PCa) patients compared with those from healthy men. The findings have shown relatively high diagnostic sensitivity, specificity and negative-predictive values for an early non-invasive screening of prostate cancer

Vascular endothelial growth factor and its receptors in the placental villi of pregnant patients with pre-eclampsia.

Comparative morphological study of the placentas from women with pre-eclampsia of different severity was carried out. The expression of vascular endothelial growth factor and its receptors (VEGFR-1, VEGFR-2, VEGFR-3) was studied by immunohistochemical methods. Branched angiogenesis processes predominated in the placentas of patients with pre-eclampsia. The syncytiocapillary membranes were thickened, the number of syncytial buds was greater than normally. Immunohistochemical studies showed high expression of VEGF and VEGFR-1 and low expression of VEGFR-2 in the placental villous structures.

Vascular endothelial growth factor and its receptors in the placenta of women with type 1 diabetes mellitus.

We performed a morphological study of placentas from women with type 1 diabetes mellitus receiving insulin therapy (insulin pump). Expression of vascular endothelial growth factor (VEGF) and its receptors (VEGFR-1, VEGFR-2, VEGFR-3) was demonstrated by immunohistochemical methods. Processes of branched angiogenesis predominated in the placentas from women with type 1 diabetes mellitus. Immunohistochemical study revealed more intensive reaction of VEGF and its receptors in syncytiotrophoblast and capillary endothelium of terminal villi.

Ligand-receptor assay for evaluation of functional activity of human recombinant VEGF and VEGFR-1 extracellular fragment.

cDNA encoding VEGF and Ig-like extracellular domains 2-4 of VEGFR-1 (sFlt-1(2-4)) were cloned into prokaryotic expression vectors pET32a and pQE60. Recombinant proteins were purified (metal affinity chromatography) and renatured. Chemiluminescent study for the interaction of recombinant VEGF and sFlt-1(2-4) showed that biotinylated VEGF specifically binds to the polystyrene-immobilized receptor extracellular fragment. Biotinylated recombinant sFlt-1 interacts with immobilized VEGF. Analysis of the interaction of immobilized recombinant VEGFR-1 and VEGF with C6 glioma cells labeled with CFDA-SE (vital fluorescent dye) showed that recombinant VEGFR-1 also binds to native membrane-associated VEGF. Recombinant VEGF was shown to bind to specific receptors expressed on the surface of C6 glioma cells. Functional activity of these proteins was confirmed by ligand-receptor assay for VEGF and VEGFR-1 (sFlt-1) and quantitative chemiluminescent detection.

[Morphological characteristics of ovarian biopsy specimens in infertility].

The authors present the results of their studies and the data available in the literature on the morphological examination of ovarian biopsy specimens in fertility. They highlight the specific features of preparation of histologic specimens. The types of male infertility and impaired spermatogenesis are given and their morphological diagnostic criteria are indicated.

Morphometric characteristics of terminal villi of the placenta in pre-eclampsia.

Comparative morphological study of the placentas from women suffering from pre-eclampsia was carried out. Morphometric studies of histological preparations showed shrinkage and low vascularization of the placental terminal villi determining the development of hypoxia.

Cloning and expression of human neuron-specific enolase cDNA in Escherichia coli.

cDNA fragment encoding neuron-specific enolase was amplified from the cDNA library of human brain. Then the fragment was cloned for expression in E. coli using the vector pET28-a. High level of neuron-specific enolase expression was confirmed by SDS-PAAG electrophoresis and immunochemical identity by immunoblot analysis. The constructed producer strain is the cheapest source of neuron-specific enolase suitable for the use in diagnostic applications.