[Preparation stimulating hair growth possibly acts by inhibiting hair follicle ageing experiments on mice and transcriptome analysis].

Preparation stimulating hair growth (PSHG) was studied on mice of various strains (Balb/c, CBA, C57BI/6, and outbred). It was shown that a long-term (44 months) application of PSHG does not reliably affect the appearance of young healthy mice but does induce increase in the hair follicle size. No adverse consequences of the PSHG application were observed. Naturally occurring propagating regenerative hair waves peculiar to mice were preserved. In older mice (more than 2 years) with signs of alopecia, application of PSHG caused an overgrowing of bald patches within two months. Transcriptome analysis of the PSHG effect performed in fibroblast cell culture showed that PSHG stimulates processes of tissue development and remodeling. These observations together with previous findings showing that PSHG stimulates autophagy and induces death of cells subjected to oxidative stress may suggest that the mechanism of the PSHG effect involves stimulation of regeneration of skin and its derivatives owing to more efficient elimination of senescent and damaged follicle cells.

[Stimulation of proliferation by carnosine: cellular and transcriptome approaches].

Concentration of endogenous dipeptide carnosine in human muscle tissue reaches tens of millimoles. For more than 100 years of research, a lot of data concerning carnosine functions were accumulated, among which anti-aging effects are regarded most important. Heire, effect of carnosine in cell cultures was studied. It has been found that apart from the known action--an increase of the Hayflick limit and morphological rejuvenation--carnosine stimulates cell division in colony-forming assays and in the course of transition of cells to the quiescent state. The analysis of the transcriptome showed that carnosine-induced changes are mainly related to positive regulation of the cell cycle at all levels, from the onset of the DNA synthesis to chromosome condensation. One can suppose that the revealed stimulation of the cell cycle account for the carnosine-induced rejuvenation processes and a high concentration ofcarnosine in muscle tissue is required for the muscle recovery (regeneration) after excess loads.

[Polymorphism of KPI-A genes from plants of the subgenus Potatoe (sect. Petota, Estolonifera and Lycopersicum) and subgenus Solanum].

Kunitz-type proteinase inhibitor proteins of group A (KPI-A) are involved in the protection of potato plants from pathogens and pests. Although sequences of large number of the KPI-A genes from different species of cultivated potato (Solanum tuberosum subsp. tuberosum) and a few genes from tomato (Solanum lycopersicum) are known to date, information about the allelic diversity of these genes in other species of the genus Solanum is lacking. In our work, the consensus sequences of the KPI-A genes were established in two species of subgenus Potatoe sect. Petota (Solanum tuberosum subsp. andigenum--5 genes and Solanum stoloniferum--2 genes) and in the subgenus Solanum (Solanum nigrum--5 genes) by amplification, cloning, sequencing and subsequent analysis. The determined sequences of KPI-A genes were 97-100% identical to known sequences of the cultivated potato of sect. Petota (cultivated potato Solanum tuberosum subsp. tuberosum) and sect. Etuberosum (S. palustre). The interspecific variability of these genes did not exceed the intraspecific variability for all studied species except Solanum lycopersicum. The distribution of highly variable and conserved sequences in the mature protein-encoding regions was uniform for all investigated KPI-A genes. However, our attempts to amplify the homologous genes using the same primers and the genomes of Solanum dulcamarum, Solanum lycopersicum and Mandragora officinarum resulted in no product formation. Phylogenetic analysis of KPI-A diversity showed that the sequences of the S. lycopersicum form independent cluster, whereas KPI-A of S. nigrum and species of sect. Etuberosum and sect. Petota are closely related and do not form species-specific subclasters. Although Solanum nigrum is resistant to all known races of economically one of the most important diseases of solanaceous plants oomycete Phytophthora infestans aminoacid sequences encoding by KPI-A genes from its genome have nearly or absolutely no differences to the same from genomes of cultivated potatoes involved by P. infestans.

[Genetic diversity and evolution of the influenza C virus].

The influenza C virus is spread worldwide and causes diseases of the upper and (less frequently) lower respiratory tract in human. The virus is not pandemic, but it circulates together with pandemic influenza A and B viruses during winter months and has quite similar clinical manifestations. The influenza C virus is also encountered in animals (pigs and dogs) and is known to override the interspecific barriers oftransmssion. The immune system of mammals often fails to recognize new antigenic variants of influenza C virus, which invariably arise in nature, resulting in outbreaks of diseases, although the structure of antigens in influenza C virus in general is much more stable than those of influenza viruses A and B. Variability of genetic information in natural isolates of viruses is determined by mutations, reassortment, and recombination. However, recombination events very rarely occur in genomes of negative-strand RNA viruses, including those of influenza, and virtually have no effect on their evolution. Unambiguous explanations for this phenomenon have thus far not been proposed. There is no proof of recombination processes in the influenza C virus genome. On the contrary, reassortant viruses derived from different strains of influenza C virus frequently appear in vitro and are likely to be common in nature. The genome of influenza C virus comprises seven segments. Based on the comparison of sequences in one of its genes (HEF), six genetic or antigenic lineages of this virus can be distinguished (Yamagata/26/81, Aichi/1/81, Mississippi/80, Taylor/1233/47, Sao Paulo/378/82, and Kanagawa/1/76). However, the available genetic data show that all the seven segments of the influenza C virus genome evolve independently.

[Increase in NETO2 gene expression is a potential molecular genetic marker in renal and lung cancers].

Multiple changes in the genome, transcriptome, and proteome are frequent in cancer cells. A search for molecular markers based on DNA, mRNA, or proteins is a main method to develop early specific diagnostics for cancer. While universal markers are still unavailable, similar trends are known for the expression patterns of particular genes in certain epithelial tumors. A bioinformatic screening of transcriptomic databases identified the NETO2 gene as a new potential promising marker of renal cancer. A substantial increase in NETO2 mRNA level was detected in 90% clear-cell renal cell carcinomas, 70% of non-small cell lung cancers, and 50% of papillary renal cancers by real-time PCR. The NETO2 mRNA level was increased to a lesser extent in cervical carcinoma and colon cancer and tended to decrease in cancer of the stomach. The NETO2 gene, which codes for a membrane glycoprotein with an unclear function, was assumed to provide a new promising marker for early diagnosis in renal cancer and non-small cell lung cancer.

[Molecular characterization of pandemic influenza viruses A/H1N1(sw2009) isolated in Russia in 2009-2010].

AIM: Assessment of genetic diversity of influenza virus A/H1N1 (sw2009) variants circulated in Russia, study of virus' pathogenicity in humans and potential resistance to antiviral drugs. MATERIALS AND METHODS: Sequencing of PCR-fragments of genome of influenza viruses isolated from clinical and autopsy samples of 436 patients. Four full genome sequences of influenza viruses A/H1N1 (sw2009) were obtained. Phylogenetic analysis was performed. RESULTS: High degree of homology (98.9-100%) was found among influenza A/H1N1(sw2009) viruses in HA and NA genes as well as in their aminoacid sequences (1.3 and 1.4% respectively). Differences in other proteins did not exceed 1.1%. Diversity was found in position 222 of receptor-binding locus of HA and single amino acid polymorphism--in several internal proteins. Known mutations determining resistance to Tamiflu and Arbidol were not detected. All viruses were resistant to remantadine. Molecular markers of high pathogenicity were not found. CONCLUSION: High homology of influenza viruses determines low level of antigenic differences although in populations of viruses there are variants with different levels of adaptation to human organism and different affinity to receptors of upper and lower respiratory tract that can determine their different transmissibility.

[Evaluation of fludarabine-containing regimens versus immunochemotherapy for chronic lymphocytic leukemia].

AIM: to analyze the efficacy of RFC (rituximab, fludarabine, and cyclophosphan), FCM (fludarabine, cyclophosphan, and mitoxantrone), and FC (fludarabine and cyclophosphan) treatment programs in patients with chronic lymphocytic leukemia (CLL) in an open-labeled comparative controlled investigation. MATERIALS AND METHODS: The paper presents the authors' results of treatment in patients with progressive CLL in 2002 to 2007. The study included 229 patients, of them 78 patients received the RFC program, 72 had the FCM program, and 79 had the FC one. RESULTS: With the use of RFC, a clinically significant therapeutic effect was obtained in 96% of the patients, a complete remission (CR) was in 80% of the primary patients and in 53% of the pretreated patients. When the FCM program was applied, a positive response was noted in 93% of the patients, CR was seen in 75 and 42% of the primary and pretreated patients, respectively. In the treatment of FC, the total effect was 80%, CR was in 41 and 14% of the primary and pretreated patients, respectively. CONCLUSION: Comparative analysis of an objective response to therapy has indicated that the effectiveness of the RFC significantly exceeds that of the FCM and FC programs, without enhancing toxicity, which allows he RFC regimen to be regarded as the program of choice in therapy for CLL.

[Pandemic influenza A/H1N1 (sw2009) in Russia: epidemiology, diagnosis, clinical picture, and treatment].

AIM: To study the epidemiological and clinical features of the 2009-2010 pandemic influenza in Russia. SUBJECTS AND METHODS: Materials from 874 patients, including postmortem samples from 287 subjects, were examined applying the AmpliSens Influenza virus A/H1-swine-FL PCR kit designed and produced by the Central Research Institute of Epidemiology. The clinical and postmortem characteristics of 68 patients who had died from influenza A/H1N1 (sw2009) were analyzed in detail. RESULTS: The cause of deaths was primary virus pneumonia in most cases. The major manifestation of viral pathogenicity was impaired microcirculation leading to hemorrhage. No mutations conferring resistance to oseltamivir and arbidol were found. All A/H1N1swl viruses had genetic markers of remantadin resistance. CONCLUSION: The reagent kits developed by the Central Research Institute of Epidemiology proved to be effective. It is necessary to set up PCR laboratories that differentially diagnose influenza and acute respiratory viral infections in health care facilities in order to make early laboratory diagnosis of influenza and to timely perform its specific therapy.

[Expression of FTL and FTH genes encoding ferretin subunits in lung and renal carcinomas].

The level of ferritin in serum is known to be increased frequently in most human cancers. Ferritin consists of the heavy and light chains, encoded by FTL and FTH genes. The analysis of the EST database showed that the level of FTL and FTH mRNA is decreased in lung squamous cell carcinomas as compared to the normal tissues, no change in the mRNA level was observed in clear cell renal cell carcinoma. Using real-time PCR we estimated the mRNA level of these genes in primary tumors. It was shown significant and frequent decrease of FTL and FTH mRNA level in lung squamous cell carcinoma: on the average by 11 and 9 times in 83% (33/40) and 73% (11/15) of cases, respectively. In clear cell renal cell carcinoma the changes were not so marked both with respect to the level of decrease (on the average 6 and 3 times) and to its frequency (58 and 27%). In the present work it has been shown for the first time that the FTL mRNA is frequently down-regulated even at the early stages of lung squamous cell carcinoma in all studied samples. This fact permits to consider this gene as potential oncomarker of early diagnosis. The FTL mRNA content may be quantified by non-concurrent hybridization on expression DNA microarrays. The possible causes of a serum ferritin increase in lung cancer and renal cancer are discussed.

[Hemostatic changes during the treatment of acute promyelocytic leukemia with all-transretinoic acid]. / Izmenenie gemostaza pri lechenii ostrogo promielotsitarnogo leikoza polnost'iu trans-retinoevoi kislotoi.

AIM: To study hemostasis in ATRA treatment of acute promyelocytic leukemia (APL). MATERIAL AND METHODS: Hemostasis was studied in 8 newly admitted APL patients treated with ATRA. All of them had hemorrhages, thrombocytopenia 5-15 x 10(9)/l at diagnosis, laboratory signs of the DIC syndrome at induction therapy. RESULTS: Hemorrhage arresting was seen on the ATRA therapy day 14 to 30. Duration of thrombocytopenia under 20 x 10(9)/l was 5.8 +/- 1.8 days. After 7 days of ATRA therapy coagulation tests improved with some hypercoagulation tendency. Subsequent condition of hemostasis was considered as normo/hypercoagulation accompanied by constant thrombin persistence (in the presence of FDP) and depression of hageman-dependent fibrinolysis even in remission. A case of ileofemoral thrombosis followed by fatal thromboembolism of the pulmonary artery is reported. CONCLUSION: It is suggested to use heparin, especially low molecular weight heparin when there are signs of hypercoagulation in APL patients.

[The use of cyclophosphane in the immunodepressive therapy of severe aplastic anemia]. / Ispol'zovanie tsiklofosfana v immunodepressivnoi terapii tiazheloi aplasticheskoi anemii.

Low course doses of cyclophosphamide (1.9 +/- 0.2 g) were given to postsplenectomy patients with grave aplastic anemia (GAA). A total of 27 patients aged 14-42 years were treated, 27 control GAA patients did not receive cyclophosphamide. The cyclophosphamide therapy was controlled by T-lymphocyte functional activity assessed in active rosette formation test with levamisole in vitro. 19 (70.3%) patients were treated twice. The remission was achieved in 22 patients (81.5%), partial response was in 1 patient (3.7%), 4 patients died (14.8%). In control subjects the remission was recorded only in 4 subjects, 23 patients died 3 to 12 months after splenectomy. It is evident that low-dose courses of cyclophosphamide are highly effective in case of control over immunological activity of the pathological process.