[Influence of connective tissue differentiation on scar tissue formation in children]. / Vliyanie differentsiatsii soedinitel'noi tkani na formirovanie rubtsovoi tkani v detskom vozraste.

OBJECTIVE: To study the immunohistochemical features of various scar tissues in children without connective tissue pathology and with undifferentiated connective tissue dysplasia syndrome. MATERIAL AND METHODS: Tissue biopsy was performed in 217 children who underwent surgical treatment for various lesions, such as injuries, burns, as well as other procedures. There were 127 boys (58.5%) and 90 (41.5%) girls. The main group consisted of 98 (48.2%) children with scar tissue; group of UCTD syndrome - 65 (30.0%) children; control group - 43 (24.8%) patients without pathological scars. Histological examination of scar tissue and intact skin was carried out during primary or redo reconstructive surgery. Immunohistochemical study of antibodies against CD34, CD105, CD140b, PDGFs, COL types I, III and IV was performed. RESULTS: The study showed a quantitative characteristic of expression of COL type I in hypertrophic scar with predominance in the main group (77.5±5.4%; p<0.05), and decrease in COL type IV. Keloid form was associated with predominance of granulation tissue in all layers of dermis and high levels of all types of collagen. In the group of UCTD, COL type III prevailed in all pathological forms of the scar. We determined quantitative indicators of expression of vascularization factors (CD34; CD105) and fibroblastic activity (CD140b; PDGFs). CONCLUSION: Understanding the process of fibrinogenesis and analysis of stages of triggering mechanisms are essential for development of preventive algorithms. Individualized approach should be considered in the treatment. These studies are especially important in children with UCTD syndrome as high-risk group for pathological scarring. Thus, further research is required.

Expression quantitative trait loci (eQTLs) in microRNA genes are enriched for schizophrenia and bipolar disorder association signals.

BACKGROUND: Schizophrenia (SZ) and bipolar disorder (BD) have substantial negative impact on the quality of human life. Both, microRNA (miRNA) expression profiling in SZ and BD postmortem brains [and genome-wide association studies (GWAS)] have implicated miRNAs in disease etiology. Here, we aim to determine whether significant GWAS signals observed in the Psychiatric Genetic Consortium (PGC) are enriched for miRNAs. METHOD: A two-stage approach was used to determine whether association signals from PGC affect miRNAs: (i) statistical assessment of enrichment using a Simes test and sum of squares test (SST) and (ii) biological evidence that quantitative trait loci (eQTL) mapping to known miRNA genes affect their expression in an independent sample of 78 postmortem brains from the Stanley Medical Research Institute. RESULTS: A total of 2567 independent single nucleotide polymorphisms (SNPs) (R2 > 0.8) were mapped locally, within 1 Mb, to all known miRNAs (miRBase v. 21). We show robust enrichment for SZ- and BD-related SNPs with miRNAs using Simes (SZ: p ≤ 0.0023, BD: p ≤ 0.038), which remained significant after adjusting for background inflation in SZ (empirical p = 0.018) and approached significance in BD (empirical p = 0.07). At a false discovery rate of 10%, we identified a total of 32 eQTLs to influence miRNA expression; 11 of these overlapped with BD. CONCLUSIONS: Our approach of integrating PGC findings with eQTL results can be used to generate specific hypotheses regarding the role of miRNAs in SZ and BD.

Genome-wide pharmacogenomic analysis of response to treatment with antipsychotics.

Schizophrenia is an often devastating neuropsychiatric illness. Understanding the genetic variation affecting response to antipsychotics is important to develop novel diagnostic tests to match individual schizophrenia patients to the most effective and safe medication. In this study, we use a genome-wide approach to detect genetic variation underlying individual differences in response to treatment with the antipsychotics olanzapine, quetiapine, risperidone, ziprasidone and perphenazine. Our sample consisted of 738 subjects with DSM-IV schizophrenia who took part in the Clinical Antipsychotic Trials of Intervention Effectiveness. Subjects were genotyped using the Affymetrix 500 K genotyping platform plus a custom 164 K chip to improve genome-wide coverage. Treatment outcome was measured using the Positive and Negative Syndrome Scale. Our criterion for genome-wide significance was a prespecified threshold that ensures that, on an average, only 10% of the significant findings are false discoveries. The top statistical result reached significance at our prespecified threshold and involved a single-nucleotide polymorphism (SNP) in an intergenic region on chromosome 4p15. In addition, SNPs in Ankyrin Repeat and Sterile Alpha Motif Domain-Containing Protein 1B (ANKS1B) and in the Contactin-Associated Protein-Like 5 gene (CNTNAP5), which mediated the effects of olanzapine and risperidone on Negative symptoms, were very close to our threshold for declaring significance. The most significant SNP in CNTNAP5 is nonsynonymous, giving rise to an amino-acid substitution. In addition to highlighting our top results, we provide all P-values for download as a resource for investigators with the requisite samples to carry out replication. This study demonstrates the potential of genome-wide association studies to discover novel genes that mediate the effects of antipsychotics, which could eventually help to tailor drug treatment to schizophrenic patients.

[Drinking mineral waters in rehabilitation of cancer patients]. / Pit'evye mineral'nye vody v vosstanovitel'nom lechenii onkologicheskikh bol'nykh.

Three hundred postmastectomy breast cancer patients and 150 patients after gastric resection for cancer have received spa treatment. It was found that a course intake of mineral water in both groups improved immune status: raised significantly the levels of T- and B-lymphocytes and their functional activity, reduced blood levels of IgG and CIC providing the phenomenon of immunological enhancement of tumor antigens. Incidence rate of postgastroresection disorders after the spa treatment fell 3.8 times, performance raised 3.1 times. The number of breast cancer recurrences decreased by 20%.

[Effect of drinking mineral water on hormonal regulation of glucose homeostasis after mastectomy for breast cancer]. / Vliianie pit'evoi mineral'noi vody na gormonal'nuiu reguliatsiiu glikogomeostaza posle mastéktomii po povodu raka molochnoi zhelezy.

Glycohomeostasis was studied in patients operated for breast cancer, healthy controls and ulcer patients before and after gastric resection (each group consisted of 12-15 examinees). Patients with duodenal ulcer had insulin hypersection including early phase reaction. Gastric resection decreases insulinemia in an early phase of reaction to oral glucose test. In postmastectomy patients insulinemia is 2-3 times higher than that in duodenal ulcer patients and 5 times higher than that in healthy subjects. Besides hyperinsulinemia, they had insulin resistance and impaired carbohydrate tolerance. A course intake of mineral water raised tissue sensitivity to insulin at early stages of glucose test and lowered basal level of insulin and hydrocortisone.

[The correction of the hormonal response during the treatment of the dumping syndrome with potable mineral waters]. / Korrektsiia gormonal'nogo otveta pri lechenii demping-sindroma pit'evymi mineral'nymi vodami.

Glucose tolerance test (40 g/lm2 b.s.) in patients with stomach resected for gastroduodenal ulcer provoked dumping-syndrome seen 15-30 min after glucose introduction. There was also a rise in blood sugar (by 77%), ACTH (by > 400%), STH (by > 400%), hydrocortisone (by 56%). Aldosterone levels fell by 68%. There was also a marked fall in activity of early insulin pool changed for elevation of its secretion by the test minute 60. 65 patients with dumping-syndrome following a course of drinking mineral water demonstrated improvement in clinical symptoms of the disease and changed hormonal response to glucose which manifested with activation of insulin secretion early phase and reduced rise of hydrocortisone levels.

[Characteristics of the sources and routes of spread of a Pseudomonas aeruginosa infection in a trauma department]. / Kharakteristika istochnikov i putei rasprostraneniia sinegnoinoi infektsii v travmatologicheskom otdelenii.

In the study of the epidemic process of P. aeruginosa infection in a traumatological hospital the leading role of patients with hospital septic infections as the sources of infection has been epidemiologically proved. Contamination has been shown to occur mostly in the pus dressing room.