[Efficacy of treatment with glucagon-like peptide receptor agonists-1 in Asian patients with type 2 diabetes mellitus].

BACKGROUND: The projected 68% increase in patients with type 2 diabetes mellitus (T2D) in the upcoming decades and the specific pathophysiological course of the disease are critical factors for the development of optimal disease management tactics in the Asian population. It is now known that ß-cell dysfunction is dominant in the pathogenesis of T2D in Asians. In a number of Asian countries, incretin therapy is the leading therapy. AIM: To review literature on glucagon-like peptide-1 (GLP-1) secretion and clinical trial results of GLP-1 receptor agonist class (GLP-1RA) drugs as well as to evaluate their effectiveness in Asian population with T2D. MATERIALS AND METHODS: A review of studies on pathophysiological aspects of GLP-1 secretion and evaluation of the efficacy of therapy with GLP-1RA preparations registered and used in clinical practice in Asian regions. RESULTS: Several studies in Asian countries have shown that intact GLP-1 levels were significantly lower in both T2D patients and healthy Japanese volunteers; as well as in patients with impaired glucose tolerance. It is suggested that either impaired secretion of GLP-1 in the gut, accelerated processing by dipeptidyl peptidase-4, or a combination of both are responsible for the decrease in GLP-1. The greater efficacy of GLP-1RA treatment in achieving glycemic control in Asian T2D patients was presented by Kim Y.G. et al. in a meta-analysis of 15 randomised controlled trials, the reduction in HbA1c on GLP-1RA treatment averaged -1.16% in Asian-dominated studies and -0.83% in non-Asian-dominated studies. In the PIONEER 9 clinical programme, similar results were obtained, with oral semaglutide having a more pronounced effect on glycaemic control in Japanese patients. Thus, the mean change in HbA 1c was -1.1%, 7 mg -1.5%, and 14 mg -1.7% at the 3 mg dose; whereas in the PIONEER 1 study in the global population, the mean change in HbA1c was -0.6%, -0.9% and -1.1% for 3, 7, 14 mg semaglutide, respectively. The PIONEER 10 study concluded that oral semaglutide was well tolerated by Japanese patients with T2D. Oral semaglutide reduced HbA1c (14 mg dose) and body weight (7 and 14 mg doses) more significantly compared to dulaglutide at 0.75 mg dose. Results of a pooled analysis of long-acting GLP-1RA showed a more significant reduction in cardiovascular event risk in the Asian subpopulation. CONCLUSION: The presented review describes benefits in glycemic control as well as in the reduction of relative cardiovascular event risks with GLP-1RA treatment in the Asian population, which requires further in-depth research and implies optimal management tactics in patients with T2DM.

[2-stage determination of rhesus classification]. / Dvukhétapnoe opredelenie rezus-prinadlezhnosti.

A new two-staged method for identifying the rhesus appurtenance of the blood is proposed. During the first stage anti-D-super (IgM monoclonal anti-D-antibodies) are used, during the second stage rhesus appurtenance is identified in a tube using standard universal reagent for determining rhesus factor RhO(D) or it is done using gelatin test with Anti-D (IgG monoclonal anti-D-antibodies). A negative result at stage 1 and positive at stage 2 is a sign of partial antigen D, most probably of the VIth category. Subjects with partial D are qualified as rhesus-positive donors and rhesus-negative recipients.

[Determination of the rhesus classification of the blood]. / K opredeleniiu rezus-prinadlezhnosti krovi.

The article describes the new two-stage method of determining of Rh-factor belonging. At the first stage tsoliclon "Anti-D-super" (monoclonic anti-D-antibody class IgM) was used. At the second stage Rh-factor belonging is determined in test-tube, using standard universal reagent for definition Rh-factor RhO (D). Combination of negative results at the first stage with positive ones at the second stage is a sign of partial antigen D, most probably category VI. The persons with partial D are qualified as Rh-positive donors and Rh-negative recipients.

[Characteristics of biochemical, electrophysiological and morphological changes in experimental cerebral ischemia]. / Osobennosti biokhimicheskikh, élektrofiziologicheskikh i morfologicheskikh izmenenii pri éksperimenta'lnoi ishemii mozga.

The results of experiments performed in Wistar rats are indicative of the catecholamine release during the first hours of developing cerebral ischemia, and their role in activation of lipid peroxidation (LP). These events were characteristically enhanced in the ischemic hemisphere where EEG changes were most pronounced. Maximal changes in slow parieto-occipital EEG waves amplitude and malonic dialdehyde levels in the brain tissue were also correlated. This metabolic-electrophysiological link than could be of major importance for EEG monitoring of brain pathochemistry and pathology needs, however, further investigation. Among pathological findings, the relationship between the degree of ischemic neuronal changes on one hand, and brain swelling and hyperemia on the another, was worth attention. The lack in distinct correlations between metabolic, electrophysiological and structural changes in the ischemic brain can be accounted for by a substantial spread of ischemic damage over the brain.

Appearance of antibodies to two viruses in cerebrospinal fluid of patients with aseptic meningitis.

Two cases of aseptic meningitis with simultaneous presence of antibodies to lymphocytic choriomeningitis (LCM) and mumps viruses were observed. In the 1st patient antibodies to both viruses appeared in sera and cerebrospinal fluid (CSF). The 2nd patient displayed rising serum antibodies to both viruses and CSF antibodies to mumps virus. Immunological findings and clinical features of the patients are discussed.

[Diagnostic significance of immunologic study of cerebrospinal fluid in neuroinfections]. / Diagnosticheskoe znachenie immunologicheskogo issledovaniia spinomozgovoi zhidkosti pri neiroinfektsiiakh.

An increase in the antibody titre in the blood serum, previously considered sufficient for determining the etiology of neuroinfection can no longer be regarded as a satisfactory index in the light of the contemporary level of our knowledge. The literature and the authors' own data show the importance of a simultaneous examination of antibodies in the cerebrospinal fluid and the blood serum in some neuroinfections. For example, the determination in the cerebrospinal fluid of antibodies to herpes simplex virus in herpetic encephalitis is considered sufficient (in the presence of the characteristic clinical picture) to make the diagnosis of this severe disease. The examination of antibodies to herpes simplex virus in the cerebrospinal fluid of 35 patients with a suspected herpetic encephalitis revealed their presence in 34% of those studied. The data obtained suggest that immunoassay of the cerebrospinal fluid and blood sera should be used on a broader scale in patients with acute and chronic neuroinfections. The method plays an the early diagnosis of these diseases and early administration of the appropriate treatment.

[Effect of different doses of dexamethasone on the course of brain injuries in animals sensitized to nerve tissue antigens]. / Vliianie razlichnykh doz deksametazona na techenie travmy mozga u zhivotnykh, sensibilizirovannykh k antigenam nervnoi tkani.

The effect of different dexamethasone doses on the development of edema of the brain in its injury was studied on 79 rabbits, controls and those sensitized with the brain antigen. The local cerebral circulation and the total tissue fluid in the perifocal region of the injured grey and white matter of the rabbit's cerebral hemispheres were studied; EEG was recorded and ultrastructural study of the nervous tissue in the zone of the trauma at the level of the ultrastructures was conducted. The examination showed that dexamethasone had a favourable therapeutic effect on the course of the brain trauma in the early periods after it was inflicted; the agent reduced edema of the brain tissue, which was especially manifest in animals with altered immunological reactivity of the organism. The best effect in these animals was caused by large doses of dexamethasone.

[Clinical forms of chronic neuroinfections (organization of research, etiology and pathogenesis, therapeutic principles)]. / Klinicheskie formy khronicheskikh neiroinfektsii (organizatsiia issledovanii étiologiia i patogenez, printsipy terapii).

The results of complex examination of 489 patients suffering from chronic neuroinfections (progressing forms of tick-borne encephalitis, disseminated sclerosis, disseminated encephalomyelitis, subacute sclerosing panencephalitis, etc.) are presented. An analysis of the results of virological, immunological, genetic and electrophysiological examinations, as well as the results of kinesotherapy has demonstrated a definite role of hereditary peculiarities of the immune mechanisms and the nervous system in the genesis of those diseases, as well as certain common features of the pathogenetic mechanisms. This enables one to outline some general principles of the therapy of those diseases.

[ABO system blood group ratios in patients with neuroinfections]. / O sootnosheniiakh grupp krovi sistemy ABO u bol'nykh neiroinfektsiiami.

The distribution of the ABO blood groups in 2009 patients including 1441 ones suffering from etiologically diverse neuroinfections was studied. Certain correlations between the nosological forms and groups of the diseases on the one hand, and the blood factors on the other are demonstrated. The data obtained point to a certain role of hereditary predisposition in the genesis of the neuroinfections. This predisposition predetermines the risk of the illnesses and the gravity of their course, the fact, which is of a practical importance for the clinician.

[Acute meningoencephalitis in children caused by herpes simplex virus type I]. / Ostrye meningoéntsefality u detei, vyzvannye virusom prostogo gerpesa I tipa.

In 14 observations of acute meningoencephalitis in children mainly under 3 years of the age, data pointing to an etiological role of herpes simplex type I virus, were obtained on laboratory examination. Six children died, and in the rest 8 children who survived gross residua were observed. The morphological picture showed extensive colliquation necroses in the parietal, temporal, and less frequently, in occipital lobes and the Varolian pons. In 4 cases out of 6 intranuclear inclusions were detected. The incidence of herpetic encephalitis was 16%.

[Immunotherapy of certain acute and chronic forms of neuroinfections (tick-borne encephalitis, multiple sclerosis, disseminated encephalomyelitis)]. / Immunoterapiia nekotorykh ostrykh i khronicheskikh form neiroinfektsii (kleshchevoi éntsefalit, rasseiannyi skleroz, rasseiannyi éntsefalomielit).

The pathogenetic community of various viral neuroinfections different in their form and course points out that the use of means targeted at correction of the immune system functions is desirable. As a result of using combined immunotherapy methods the authors have obtained positive results in treating 38 patients suffering from some acute and chronic neuroinfections (grave local forms of acute tick-borne encephalitis, progredient forms of the same encephalitis, disseminated sclerosis, disseminated encephalomyelitis). Interrelations between the immunity factors are studied, and their role in the therapeutic effect obtained is discussed. The scheme and the result of the treatment, as well as general principles of dynamic observation and treatment of those patients are presented.

[Synthesis of multiple forms of brain cholinesterases]. / Sintez mnozhestvennykh form kholinésterazy mozga.

Highly purified multiple forms of brain cholinesterase were isolated by a new method. Eight forms were identified as acetyl cholinesterases, seven forms--as butyryl cholinesterases, four forms--as mixed acetyl- and butyryl cholinesterases and four forms--as aliesterases. Biosynthesis of multiple forms of brain cholinesterase was monitored by following incorporation of 14C-glycine into the purified fractions. Cats were killed at different periods (3 hrs, 3,6 and 9 days) after intoxication with isopropyl hydroxymethyl fluorophosphate. The restoration of the enzymatic activity after the inhibition did not correspond to the incorporation of the labelled amino acid into the enzyme protein. There was a transcient increase in the incorporation of the label after an increase in acetylcholine concentration.