Neurohumoral markers that predict the efficiency of pharmacologic therapy of depressive disorders

We present a comprehensive clinical and biological study of 46 patients with depressive disorder (F32-F33: depressive episode and recurrent depressive disorder) during pharmacotherapy. Neurohumoral factors (cortisol, brain-derived neurotrophic factor, serotonin, DHEA and its sulfated form) were determined in serum by ELISA. The severity of the current depressive episode was evaluated using the 17-point Hamilton Depression Rating Scale (HDRS-17); the pharmacotherapy efficacy was evaluated using the scale of the Clinical Global Impression (CGI Scale). We showed that before prescription of pharmacotherapy peripheral blood neurohumoral markers that characterize the state of stress-realizing and stress-limiting systems of the body may be considered as biological predictors of the effective pharmacotherapy of a current depressive episode and used as additional paraclinical examination methods. At higher concentrations of cortisol and serotonin associated with a decrease in the content of neurosteroid dehydroepiandrosterone, the high efficiency of the pharmacotherapy of depressive episode is predicted

КОНВЕРСИОННАЯ ХИМИОТЕРАПИЯ В ЛЕЧЕНИИ МЕСТНОРАСПРОСТРАНЕННОГО РАКА ПРЯМОЙ КИШКИ

We present a case report of locally advanced colorectal cancer that responded successfully to conservation chemotherapy allowing R resection to be performed.   Morphological characteristics prior to and after chemotherapy have been described in detail. This case report demonstrates the feasibility of performing radical treatment for patients with locally advanced rectal cancer using neoadjuvant chemotherapy.Представлено клиническое наблюдение успешного применения конверсионной химиотерапии у пациента с местнораспространенным колоректальным раком, которая позволила выполнить оперативное вмешательство R0 у пациента, отнесенного ранее к группе нерезектабельных. Подробно представлены диагностический комплекс и особенности морфологической диагностики до и после химиотерапии. Данное наблюдение демонстрирует возможность проведения радикального лечения больных с местнораспространенным раком прямой кишки с применением неоадъювантной химиотерапии

SIRT1 Allele Frequencies in Depressed Patients of European Descent in Russia

Depressive disorder (DD) is a widespread mental disorder. Although DD is to some extent inherited, the genes contributing to the risk of this disorder and its genetic mechanisms remain poorly understood. A recent large-scale genome-wide association Chinese study revealed a strong association between the SIRT1 gene variants and DD. The aim of this study was to analyze the occurrence of heterozygote carriers and search for rare SNP variants of the SIRT1 gene in a cohort of DD patients as compared with a cohort of randomly selected members of the Russian population. The complete coding sequences of the SIRT1 gene from 1024 DNA samples from the general Russian population and from 244 samples from patients with DD were analyzed using targeted sequencing. Four new genetic variants of the SIRT1 were discovered. While no significant differences in the allele frequencies were found between the DD patients and the general population, differences between the frequencies of homozygote carriers of specific alleles and occurrences of heterozygous were found to be significant for rs2236318 (P < 0.0001), and putatively, rs7896005 (P < 0.05), and rs36107781 (P < 0.05). The study found for the first time that two new SNPs (i.e., 10:69665829 and 10:69665971) along with recently reported ones (rs773025707 and rs34701705), are putatively associated with DD. The revealed DD-associated SIRT1 SNPs might confer susceptibility to this disorder in Russian population of European descent

Neurohumoral markers that predict the efficiency of pharmacologic therapy of depressive disorders

We present a comprehensive clinical and biological study of 46 patients with depressive disorder (F32-F33: depressive episode and recurrent depressive disorder) during pharmacotherapy. Neurohumoral factors (cortisol, brain-derived neurotrophic factor, serotonin, DHEA and its sulfated form) were determined in serum by ELISA. The severity of the current depressive episode was evaluated using the 17-point Hamilton Depression Rating Scale (HDRS-17); the pharmacotherapy efficacy was evaluated using the scale of the Clinical Global Impression (CGI Scale). We showed that before prescription of pharmacotherapy peripheral blood neurohumoral markers that characterize the state of stress-realizing and stress-limiting systems of the body may be considered as biological predictors of the effective pharmacotherapy of a current depressive episode and used as additional paraclinical examination methods. At higher concentrations of cortisol and serotonin associated with a decrease in the content of neurosteroid dehydroepiandrosterone, the high efficiency of the pharmacotherapy of depressive episode is predicted

The study of dopamine receptor genes in patients with schizophrenia

Background: Schizophrenia is a severe mental disorder, usually treated with long-term anti-dopaminergic therapy. Although several theories have been lanced, pathophysiology of schizophrenia has not yet been elucidated. Identifying genetic factors contributing to development of schizophrenia would be of considerable interest for personalizing treatment [1]. Most studies in the field of pharmacogenetics of schizophrenia are based on the study of receptor candidate genes or secondary messengers (pharmacodynamic components) and that of drug metabolizing enzymes (pharmacokinetic components), or suspected loci to the disease schizophrenia (pathogenetic components). An important role in personalization of treatment is played by the suitability of drugs targeting dopamine receptors [2]. Objective: to investigate role of 28 SNP's of dopamine receptor genes DRD1, DRD2, DRD2/ANKK1, DRD3, DRD4 as a potential markers of schizophrenia in patients of Russian population. Methods: Fourhundred and seventy (470) patients with schizophrenia and 127 healthy controls were investigated. Mean age was 42.1 ± 12.4 for patients, for healthy group is 38.5 ± 13.2 years. Mean duration of disease was 13 years for schizophrenic patients. The inclusion criteria were a clinical diagnosis of schizophrenia, according to the International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10: F20), and age 18–75 years old. We used the standard phenol-chloroform method for isolation DNA from whole peripheral blood. Genotyping was carried out on 28 SNPs of dopamine receptors (rs6275, rs1801028, rs4245147, rs134655, rs6277, rs1076560, rs2283265, rs179997, rs6279, rs1076562, rs2734842, rs4532, rs936461, rs2734849, rs11721264, rs167770, rs3773678, rs963468, rs7633291, rs2134655, rs9817063, rs324035, rs1800828, rs167771, rs6280, rs1587756, rs3758653, rs11246226). We were employed the MassARRAY® Analyzer 4 (Agena Bioscience™) and using the kit iPLEX Gold 384. Statistical analysis was carried out with SPSS software, release 17. Statistical significance of tested associations was considered for significance at a P-value less than 0.05. Results: This study was carried out in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki 1975, revised in Fortaleza, Brazil, 2013), established for experiments involving humans. We recruited patients from three psychiatric hospitals located in the Tomsk, Kemerovo, and Chita oblasts (regions) of Siberia, Russia. Healthy control group was recruited from the same region with identical characteristics, comparable in gender and age. The distribution of genotypes of studied genes corresponded to the Hardy-Weinberg equilibrium. We got statistically significant results for alleles of polymorphic variant rs3773678 of DRD3 receptor gene (c2 = 4.940, p = 0.030). We found that allele C are significantly associated with protective effect (odds ratio is 0.53 [95% CI: 0.30 - 0.94]) and allele T are significantly associated with predisposing effect on the development of schizophrenia (odds ratio is 1.88 [95% CI: 1.07 - 3.29]). Conclusion: According to literature data polymorphisms of dopamine receptors genes play important role in the therapy of schizophrenia. A polymorphic variant of one dopamine receptor gene has been identified, whose alleles have predisposing and protective effects for patients in the pathogenesis of schizophrenia. Acknowledgement: This work was supported by the comprehensive program of fundamental scientific research of the SB RAS ``Interdisciplinary Integrated Studies'' (2018-2020), project No. 3

EFFICACY AND SAFETY OF ALBAREL IN PATIENTS WITH MILD, MODERATE AND SEVERE HYPERTENSION

The aim of the study was to evaluate the efficacy and safety (influence on carbohydrate, lipid and mineral metabolism, as well as nitrogen-excreting function of kidneys) of monotherapy with rilmenidine in patients with mild to moderate AH, as well as treatment of patients with severe AH as multiple combined treatment. 43 patients with essential AH I-HI degree, aged 22 to 79, were enrolled in this open label study after signing an informed consent form. Enrolled patients were divided into 2 groups. Group 1 included 20 outpatients. They received monotherapy with rilmenidine 1 mg daily. Duration of treatment was 12 weeks. Group 2 was comprised of 23 subjects admitted to an in-patient clinic. Those subjects received Albarel 1 mg or 2 mg daily as a component of multiple antihypertensive therapy. Albarel was administered 7-10 days following the admission to clinic as a second to fifth hypotensive drug. Albarel's combinations with diuretics, ACE inhibitors, calcium antagonists, beta-blockers. The result is - monotherapy with Albarel 1-2 mg daily allows to achieve target BP in 77, 8 % patients with mild to moderate AH. With Albarel as a component of multiple therapy target BP is achieved in 65, 2 % patients with severe AH. Effectively decreasing BP Albarel does not change its daily profile. It has no influence on renal function, carbohydrate metabolism, and electrolyte content of blood. Albarel is well tolerated. Adverse effects included mouth dryness and drowsiness, was noted in 2, 33 % cases and did not require drug withdrawal

CONVERSION CHEMOTHERAPY FOR LOCALLY ADVANCED RECTAL CANCER: A CASE REPORT

We present a case report of locally advanced colorectal cancer that responded successfully to conservation chemotherapy allowing R resection to be performed.   Morphological characteristics prior to and after chemotherapy have been described in detail. This case report demonstrates the feasibility of performing radical treatment for patients with locally advanced rectal cancer using neoadjuvant chemotherapy