A new insight into mechanisms of interferon alpha neurotoxicity: Expression of GRIN3A subunit of NMDA receptors and NMDA-evoked exocytosis.

Neurological and psychiatric side effects accompany the high-dose interferon-alpha (IFNA) therapy. The primary genes responsible for these complications are mostly unknown. Our genome-wide search in mouse and rat genomes for the conservative genes containing IFN-stimulated response elements (ISRE) in their promoters revealed a new potential target gene of IFNA, Grin3α, which encodes the 3A subunit of NMDA receptor. This study aimed to explore the impact of IFNA on the expression of Grin3α and Ifnα genes and neurotransmitters endo/exocytosis in the mouse brain. We administered recombinant human IFN-alpha 2b (rhIFN-α2b) intracranially, and 24 h later, we isolated six brain regions and used the samples for RT-qPCR and western blot analysis. Synaptosomes were isolated from the cortex to analyze endo/exocytosis with acridine orange and L-[14C]glutamate. IFNA induced an increase in Grin3α mRNA and GRIN3A protein, but a decrease in Ifnα mRNA and protein. IFNA did not affect the accumulation and distribution of L-[14C]glutamate and acridine orange between synaptosomes and the extra-synaptosomal space. It caused the more significant acridine orange release activated by NMDA or glutamate than from control mice's synaptosomes. In response to IFNA, the newly discovered association between elevated Grin3α expression and NMDA- and glutamate-evoked neurotransmitters release from synaptosomes implies a new molecular mechanism of IFNA neurotoxicity.

[Obtaining and characteristics of domestic preparation interferon alpha-2b with prolonged effect].

Pegylated interferon alpha-2b (PEG-IFN alpha-2b) is a domestic preparation of a modified recombinant interferon alpha-2b with prolonged effect. The preparation was obtained by N-terminal pegylation of IFN alpha-2b with polyethylene glycol (PEG). This paper presents the method of PEG-IFN alpha-2b synthesis and characteristics of the obtained product. PAAG electrophoresis, Western blot analysis and MALDI-TOF mass-spectrometry confirm that the preparation is an N-terminal pegylated IFN alpha-2b that contains no more than 10% of dipegylated IFN alpha-2b. The comparison of PEG-IFN alpha-2b with its foreign analogue has revealed the similarity of their biological activity and pharmacokinetic parameters.

[New ways to increasing the yield of laccase from Panus tigrinus fungi].

We optimized the conditions for production of laccase by lignolytic fungi Panus tigrinus 8/18. 2,4-Dimethylphenol was used as an aromatic inductor. The addition of 2,4-dimethylphenol and 2 mM CuSO4 to a rich medium was followed by a tenfold increase in the yield of this enzyme. Additional treatment of the medium with perftoran (oxygen-carrying agent) and immobilization of the fungus on polycaproamide fibers increased significantly laccase activity in the medium. The conditions for cultivation of P. tigrinus fungi were optimized. It allowed us to increase laccase activity in the medium by 25 times (compared to activity of the enzyme obtained with previously described methods).

[Hormonal correction of the resident microflora of the vagina and uterus cervix in women with chronic cervicitis]. / Gormonal'naia korrektsiia rezidentnoi mikroflory vlagalishcha i sheiki matki u zhenshchin s khronicheskimi tservitsitami.

Clinical, microbiological and hormonal examination of women with chronic cervicitis revealed lesions in the upper section of the reproductive tract in a high proportion of those examined, hormonal disturbances being registered in 96.7% of women. Dysbiotic manifestations (suppression of lacto- and bifidoflora and the excessive growth of opportunistic microorganisms) in the uterus cervix and vagina observed in patients with chronic cervititis were not associated with the etiology of the inflammatory process. The degree of dysmicrobiocenosis in the lower section of the genital tract in women with chronic cervicitis depends on the character of hormonal disturbances. The most significant inhibition of the resident flora was observed when ovarian dysfunction occurred and less significant--in cases of hyperprolactinemia and changes in the level of hypophysial hormones. Hormonal disturbances led to contamination of vagina and cervical canal with opportunistic microorganisms that was inversely proportional to the presence of lactic acid bacteria and bifidobacteria in these organs. Complex therapy of women with chronic cervicitis with the use of preparations for the correction of hormonal disturbances made it possible to restore the normal microflora of the genital tract and to improve the results of treatment.

[The possibility for the intravital diagnosis of a dissecting aortic aneurysm]. / O vozmozhnosti prizhiznennoi diagnostiki rasslaivaiushchei anevrizmy aorty.

On the basis of experience gained in vital diagnosis of dissecting aneurysm, its thoracic portion, in 3 patients the authors note that accurate diagnosis of this pathology cannot be made without analysis of a complex of diagnostic studies that rely on a correct assessment of clinical manifestations of the disease. The following items should be noted: particular features of the pain syndrome, migration of the pain zone and relapsing character of pain; lack of a clear-cut interrelation between intensity and duration of pain and frequency of development of cardiogenic shock and cardial asthma; correlation between changes in blood count (leukocytosis) and blood levels of transaminases; absence of the typical ECG features of myocardial infarction, and character of time-related changes.

[Evaluation of diagnostic indices of reactivity during treatment of patients with chronic bronchitis and bronchiectatic disease]. / Otsenka nekotorykh diagnosticheskikh pokazatelei reaktivnosti organizma v protsesse lecheniia bol'nykh khronicheskim bronkhitom i bronkhoéktaticheskoi bolezn'iu.

Evaluation of neutrophils conditions by glycogen, enzymatic activity (acid and alkaline phosphatases, peroxidase), lymphocyte blast-transformation reaction stimulated by staphylococcal antigen in 113 patients with bronchial pathology on treatment suggested the conclusion of their value in verification of the disease course correction of on-going treatment and definition of its effect. The methods acquire additional significance in objective assessment of the process activity in obscure clinical manifestations and lack of laboratory evidence for aggravation.

[The dynamics of the indices of reactivity of the body in patients with chronic bronchitis and bronchiectasis in the course of treatment]. / Dinamika pokazatelei reaktivnosti organizma u bol'nykh khronicheskim bronkhitom i bronkhoéktaticheskoi bolezn'iu v protsesse lecheniia.

Complex determination of lymphocyte functional activity and the condition of the organism's immunological values in patients with chronic bronchitis and bronchiectasis helps in obtaining additional objective information which makes it possible to appraise the severity of the course of the disease, correct the treatment and determine its efficacy in different stages of the disease, come to a decision in regard to operative intervention, and form a judgement on the fullness of recovery. These tests acquire additional diagnostic value in patients with mild clinical manifestations of the disease as well as in the absence of its laboratory signs. A direct dependence between the severity of the disease and the above named values was revealed.

[The significance of body reactivity indices for the diagnosis and treatment of acute pneumonia]. / Znachenie nekotorykh pokazatelei reaktivnosti organizma dlia diagnostiki i lecheniia ostroi pnevmonii.

The assessment of lymphocytic functional activity and immunological reactivity in 114 cases of acute pneumonia provided additional information on the disease severity, potential complications, effectiveness of the treatment conducted, completeness of recovery. The study of immunological reactivity in acute pneumonia is beneficial in poor clinico-roentgenological manifestations. Combined treatment with levamisole promoted improvement of immunological reactivity and reduced the duration of disability.

[The immunological reactivity indices of patients with chronic nonspecific lung diseases]. / Nekotorye pokazateli immunologicheskoi reaktivnosti bol'nykh khronicheskimi nespetsificheskimi zabolevaniiami legkikh.

At height of the disease patients with chronic bronchitis showed a reduction of immunological indices of reactivity of the body. A direct dependence was established between the severity of the course of the disease and degree of reactivity reduction. Absence of complete normalization of indices of immunological reactivity at discharge from the clinic indicates incomplete control of the inflammatory process and short-term character of the remission. The reaction of lymphocyte blast transformation may be used for detection of both latent and clinically manifest staphylococcal infection. Increased sensitivity to staphylococcal allergen results in a reduction of the phagocytic activity of neutrophils in patients with chronic bronchitis.

[The value of determining antibodies to DNA in patients with purulent diseases of the lungs]. / Znachenie opredeleniia antitel k DNK u bol'nykh s nagnoitel'nymi zabolevaniiami legkikh.

Anti-DNA antibody titers are elevated in the patients with purulent diseases of the lungs and antibodies to nDNA appear that are undetectable in normal subjects. These data correlate with the inflammatory process activity in the lungs, with the diameter of the decayed cavity, disease duration, and efficacy of therapy. Dynamic titration of antibodies to DNA (particularly nDNA) over the course of the disease appears to be an important prognostic test reflecting the stability of autoimmune impairments and the efficacy of the therapeutic scheme used in the treatment of patients with purulent diseases of the lungs.

[Correction of hepatic morphofunctional disorders in mechanical jaundice of a nontumorous nature]. / Korrektsiia morfofunktsional'nykh narushenii pecheni pri mekhanicheskoi zheltukhe neopukholevoi prirody.

The authors examined 68 patients with cholelithiasis complicated by mechanical jaundice. The clinical course of the disease, functional and morphological changes of the liver were elucidated. Different hepatic functions were involved: the protein-forming, pigmentary, enzymatic, etc. Morphological changes of the liver revealed severe dystrophic changes in the liver parenchyma including necrosis of some parts the liver. The employed complex of therapeutic measures allowed to carry out operative interventions in more favourable conditions that reduced the number of postoperative complications.

[Difficulties in the diagnosis of primary cancer of the liver]. / O trudnostiakh diagnostiki pervichnogo raka pecheni.

Case records have been analyzed for 92 patients with primary cancer of the liver. The discrepancies between the clinical and postmortem diagnosis reached 31%. It appeared that the exact diagnosis depended on valid evaluation of the disease history, clinical signs and findings at special examinations rather than on the number of investigations. Associated liver cirrhosis recorded in 24% of cases put another obstacle for a precise vital diagnosis. The study has furnished evidence for a judgment on the incidence of hepatic cancer, concomitant cirrhosis, possible etiologic factors, the state of clinical diagnosis and causes of death.

[Levamisole and splenin in combined therapy of patients with bronchiectasis]. / Levamizol i splenin v kompleksnoi terapii bol'nykh bronkhoéktaticheskoi bolezn'iu.

Follow-up of 114 patients with bronchiectasis has demonstrated that immunomodulation agents levamisole and splenin included in combined treatment augment their therapeutic effect and normalize the immune status of patients. This is manifested by normalization of the amount and functional activity to T-lymphocytes, the content of IgG, IgM and IgA and the autoimmune shifts. A favourable effect was encountered significantly more often than that in patient who were treated by the traditional methods without the use of the immunomodulation agents and in those who were given only levamisole and splenin together with anti-bacterial and hygienic therapy.

[Differential diagnosis in fever of unknown origin]. / O differentsial'noi diagnostike pri likhoradke neiasnogo geneza.

A study of 156 patients admitted to the clinic with the diagnosis of "fever of unclear genesis" indicates that the most frequent cause of this condition are pathological processes in the abdominal and retroperitoneal space, renal diseases, patients with bacterial endocarditis and connective tissue diseases. Detailed clinical analysis makes it possible mostly to establish a correct diagnosis at early terms of the disease.

[The treatment of peptic ulcer]. / O lechenii iazvennoi bolezni.

Problems are discussed on the differential pathogenetic treatment of patients with duodenal ulcer. Variants are singled out of the course of ulcer disease depending on the prevalence of clinical symptoms. The characteristic features of these symptoms are described and the most rational and individualized therapeutic complexes for each of these clinical variants are evaluated.