[New clinical guidelines for COPD - a paradigm shift: A review].

Chronic obstructive pulmonary disease is now one of the most common noncommunicable diseases and the main causes of morbidity, disability and mortality in the world. In recent years, new approaches to epidemiology, diagnosis, classification (categorization), evaluation of phenotypes, as well as characterization and assessment of the severity of сhronic obstructive pulmonary disease exacerbations have emerged. Modern approaches to starting and subsequent drug therapy have changed significantly. This is largely due to the results of recently conducted major clinical trials, demonstrated high efficacy of triple fixed combinations, including inhaled glucocorticosteroids, long-acting beta-agonists and long-acting anticholinergic drugs. The use of non-medication methods (smoking cessation, physical activity and respiratory rehabilitation) and modern approaches to the treatment of respiratory failure and antibiotic therapy remain important. In terms of their significance, all these updates have a significant impact on real clinical practice and can be considered as a novel paradigm of the approaches to the diagnosis and management of this disease.

[Peculiarities of Mild Asthma in Russia: the Results of SYGMA2 Study].

AIM: Patients with mild asthma may experience severe exacerbations. This analysis was conducted to investigate regional peculiarities of mild asthma population in Russia. MATERIALS AND METHODS: The SYGMA2 is a double-blind multinational study involving adult patients with mild asthma (n=4176). We conducted an open-label descriptive analysis of the baseline characteristics of the Russian group (n=579) of SYGMA2 trial comparing to SYGMA2 population from other countries. The subanalysis was descriptive only, and no hypothesis were tested. RESULTS: The Russian population of patients with mild asthma was comparable to the rest of countries in terms of demographic characteristics, smoking status and duration of asthma. The spirometric parameters in the Russian group was slightly worse than in the other population. At the study entry 48% of Russian patients had symptom control on maintenance therapy, but 52% were uncontrolled on short-acting bronchodilators. While in other countries this ratio was inverse (55/45%). More patients with mild asthma in the Russian group had at least one severe exacerbation in the previous year (30.1% vs 20.7% in other countries). CONCLUSION: We revealed a delayed prescription of controller therapy and overuse of short-acting bronchodilators in the Russian group of mild asthma patients, that may increase risk of asthma non-control and severe exacerbation.

Correction of oxidative stress in patients with chronic cerebral ischemia.

A pilot study of the effect of the antioxidant drug ethylmethylhydroxypyridine malate on indicators of oxidative stress in patients with chronic cerebral ischemia. At 6 day course administration investigated the antioxidant in these patients significantly accelerates the process of generation of superoxide anion radical, established by lucigenin-depended chemiluminescence that probably regulate a feedback mechanism oxidase systems. This increases the activity of superoxide dismutase, and reduced the concentration of secondary peroxidation product - malondialdehyde, making reasonable use of antioxidants in the treatment of this pathology.

[Results of clinical studies of the efficacy and safety of the use of ethylmethylhydroxypyridine succinate in patients with chronic cerebral ischemia]. / Rezul'taty klinicheskikh issledovanii effektivnosti i bezopasnosti primeneniya preparatov etilmetilgidroksipiridina suktsinata u patsientov s khronicheskoi ishemiei golovnogo mozga.

Chronic cerebral ischemia (CCI) is a common syndrome that, in the absence of adequate therapy, is characterized by a progressive course, an increase in cognitive, emotional, motor and other disorders, eventually leading to persistent disability of the patient. In the treatment of patients with CCI, the use of drugs with a multimodal neuroprotective effect is indicated. The results of the analysis of a series of clinical trials of the drugs Mexidol and Mexidol FORTE in patients with CCI are presented. The effects in relation to cognitive, emotional, asthenic, vegetative and other manifestations of CCI are considered. It is concluded that it is advisable to consistently use the drugs Mexidol and Mexidol FORTE in such patients.

[The efficacy of ethylmethylhydroxypyridine in the rehabilitation treatment of poststroke patients]. / Effektivnost' primeneniya etilmetilgidroksipiridina suktsinata v vosstanovitel'nom lechenii patsientov, perenesshikh ishemicheskii insul't.

The analysis of the clinical efficacy and safety of ethylmethylhydroxypyridine succinate (mexidol) in the complex of rehabilitation measures in patients after ischemic stroke (IS) shows that course treatment with mexidol improves the recovery of neurological functions, decreases neurological deficit, cognitive disorders, including memory impairment, and manifestations of asthenic syndrome, increases the level of social adaptation and improves the psycho-emotional state of patients, reduces spasticity, increases motor and speech activity, praxis, reliably eliminates the ignoring syndrome. There is a decrease in the level of total cholesterol and low-density b-lipoproteins in the blood, and decrease in the severity of hypercoagulation. The results of the studies have convincingly shown the efficacy of mexidol at all stages of rehabilitation treatment of patients with IS.

[Efficacy and safety of ethylmethylhydroxypyridine succinate in patients with chronic cerebral ischemia]. / Effektivnost' i bezopasnost' primeneniya etilmetilgidroksipiridina suktsinata u patsientov s khronicheskoi ishemiei golovnogo mozga.

Chronic cerebral ischemia (CCI) is a common cerebrovascular syndrome, the development of which is associated with a high risk of increasing cognitive, behavioral, and motor disorders, and the formation of a patient's dependence on others. Timely start of treatment can slow down the course of the disease, make it more favorable. The review considers the possibility of using the domestic neuroprotector mexidol in patients with CCI. The results of a series of clinical studies on the use of ethylmethylhydroxypyridine succinate (mexidol) in patients with CCI are analyzed. The effectiveness of the drug in relieving cognitive, affective and motor disorders is noted. Information about the good tolerance of mexidol is presented.

[Efficacy and safety of ethylmethylhydroxypyridine succinate in patients with ischemic stroke]. / Effektivnost' i bezopasnost' primeneniya etilmetilgidroksipiridina suktsinata u patsientov s ostrym ishemicheskim insul'tom.

Stroke is still the most significant problem of the modern medicine and the leading cause of mortality and morbidity. There is the great experience of neuroprotection in patients with stroke in the Russian Federation. In clinical practice it's important to follow conditions, where neuroprotection will have maximum safety and effectiveness. The clinical trials of ethylmethylhydroxypyridine succinate (mexidol) in patients with acute ischemic stroke are described in the present review. Early management (in the first 6 hours) with mexidol significantly improve recovery dynamic and stroke outcome. Therapy with mexidol increases neurological recovery, improves vital activity and quality of life of patients with stroke. Furthermore, mexidol demonstrates high safety profile.

[Mutations of the Epstein-Barr virus LMP1 gene mutations in Russian patients with lymphoid pathology and healthy individuals].

Epstein-Barr virus (EBV) is an etiological agent of a number of benign and malignant human diseases, such as infectious mononucleosis (IM), Hodgkin's lymphoma (HL), and non-Hodgkin's lymphoma (NHL). EBV latent membrane protein 1 (LMP1) gene (recognized as a viral oncoprotein) of various clinical and geographical origin was found to have different types of amino acid mutations affecting its biological activity. Since there was no information on the strain differences in LMP1 of EBV persisting in Russia, the authors made a sequence analysis of LMP1 samples amplified from the biological materials of Russian patients with IM, HL, and NHL and healthy individuals. The studies have shown that LMP1 variants of Russian origin are a mixed heterogeneous group containing both the earlier characterized and presumably new genetic variants. Among the point amino avid substitutions, the mutations S366T, F106Y, 185L, and E328Q associated with the enhanced transforming activity of a LMP1 molecule and its reduced cytotoxicity. There was no specific association between the certain Russian variants of LMP1 and the specific forms of the disease (IM, HL, and NHL).

[A clinicoeconomic model of basic therapy for bronchial asthma].

The paper is dedicated to analysis of the most wide-spread variants of bronchial asthma (BA) basic therapy. The analysis was based on the results of a large (1362 patients from 34 Russian cities) pharmacoepidemiological study. Different models of pharmacotherapy were assessed on the basis of clinical data (the frequency of symptoms), the risk of BA exacerbation, the volume of public health resources used, and the cost of treatment. The results of the study showed that the use of set combinations of inhaled glucocorticosteroids and long-acting , beta2-adrenostimulators was most effective and rational from economic perspective under real clinical conditions.

[Controlled cell cultivation. V. The effect of various rubbers on the isolated neurons of Limnaea stagnalis in culture]. / Upravliaemoe kul'tivirovanie kletok. V. Vliianie nekotorykh rezin na izolirovannye neirony Limnaea stagnalis v kul'ture.

Various domestic rubbers were tested for toxicity to cultured isolated neurons of Lymnaea stagnalis, the survival time of these cells, and their morphological differentiation being used as criteria. According to the effect towards the neurons, the tested materials could be divided into inert, low-toxic, and toxic ones. Type 52336/4 silicon rubber, the rubber of surgical gloves, and dry rubber of "b" type produce no unfavourable effect on isolated neurons. Stoppers of penicillin bottles, baby's dummies, and silicon-based BgO-1 "Germetic" paste are low-toxic rubbers. By contrast, silicon rubbers of 52336 and 14p-6 types, KLT-30 silicon paste and black rubber of HO-68-1 type decreased sharply the survival time of the neurons and depressed their morphological differentiation in culture.

[Fibroblast behavior in weak substrate adhesion]. / Povedenie fibroblastov v usloviiakh slaboi adgezii k substratu.

Primary human embryonic fibroblasts and permanent line of fibroblasts BHK-21 were cultivated on the glass in the medium, containing bovine serum ultrafiltrate with the molecular weight of the components up to 70000 D, and on liquid perfluorocarbon, perfluorotributylamine in the normal growth medium. In both the cases one could observe a formation of aggregates, however, in the case of cultivating the primary fibroblasts on the glass the aggregation was much less pronounced. The formation of aggregates is considered to be the result of the reduced adhesion of cells to the substrate. In the first case the low adhesion is accounted for by the deficiency of the adhesion factors, and in the second case--by the physico-chemical properties of the liquid substrate used.

[Growth of lymphoid cell cultures of the Raji line in a medium containing low-molecular serum components]. / Rost kul'tur limfoidnykh kletok linii Raji v srede, soderzhashchei nizkomolekuliarnye komponenty syvorotki.

The effect of fetal bovine serum ultrafiltrate, containing low-molecular components (lower than 14 000 D), on the growth of cultures of the lymphoid Raji cells and fibroblasts BHK-21 was studied. The growth of the former did not differ from that in the control (in the medium with the whole fetal serum), while the latter did not proliferate in the medium with the ultrafiltrate. Thus, the growth of the lymphoid Raji cells and fibroblasts BHK-21 is controlled by different serum components. The Raji cells were exposed to an ultrafiltrate (up to 14 000 D) of the adult animal serum whose growth stimulating activity is known to be lower than that of the fetal serum. After the removal of components with molecular weights higher than 14 000 D from the adult animal serum, the growth stimulating activity of such a serum was seen increased, but not up to the level of the fetal serum. BHK-21 cells did not proliferate in the medium with this ultrafiltrate. It is proposed that the increase in the growth stimulating activity of the whole bovine serum in respect to the Raji cells after the removal of the components with high molecular weights may be due to the removal of lymphocyte growth inhibitors whose activity depends on the age of the animal serving a donor of serum.

[Controlled cell cultivation. III. The flow-diffusion chamber]. / Upravliaemoe kul'tirovanie kletok. III. Protochno-diffuzionnaia kamera.

A perfuse chamber is described intended for a continuous culturing of cells and tissues, for in vitro observations and for the screening of biologically active substances. The chamber is dismountable. A ring-shaped partition of the chamber, separating the pericellular zone from the external flowing one, contains to diametrically opposite diffuse filters in the form of cylindrical stoppers made of porous glass. Depending on the angle of rotation of the diffuse filter axis with respect to the axis of pipe connections of the chamber, the wanted rate of material transfer between pericellular and flowing zones is achieved. Biological tests have shown that the survival time of isolated molluscan neurones of Limnaea stagnalis in this chamber considerably exceeds that in conventional perfusion chambers without partition. The chamber can be used in studies of embryogenesis, for incubating fertilized oocytes under conditions of controlled culturing.

[Controlled cell cultivation. IV. The cultivation of isolated neurons of the mollusc, Limnaea stagnalis, in a flow-diffusion chamber]. / Upravliaemoe kul'tirovanie kletok. IV. Kul'tivirovanie izolirovannykh neironov molliuska Limnaea stagnalis v protochno-diffuzionnoi kamere.

A possibility of the long-term cultivation of isolated neurons of adult molluscs Limnaea stagnalis in a flow-diffusion chamber has been shown. The construction of the chamber is described by the authors elsewhere; the diagram of the pefusion apparatus has been presented. In the process of cultivation, the nerve cells undergo morphological differentiation to form neuron nets on the glass that involve both individual neurons and their aggregates of 2 to 5 cells. By days 16-18 of cultivation, most of the neurons join together to form several large aggregates of 10-40 cells, connected to each other by thick nerve fibre bundles. A sharp decrease of survival time and the complete inhibition of morphological differentiation of neurons was observed when the diffusional exchange between the extracelluar space and the flowing nutrient medium was replaced in the chamber by the medium perfusion through the extracellular (=pericellular) space. The cause of this phenomenon is discussed.

[Structural and functional features of Epstein-Barr virus LMP-1 gene in patients with anaplastic carcinoma of the nasopharynx in Russia]. / Strukturnye i funktsional'nye osobennosti gena LMP-1 virusa Epshteina-Barr u bol'nykh nedifferentsirovannym rakom nosoglotki v Rossii.

Epstein-Barr virus (EBV) is known to be closely associated with the development of anaplastic nasopharyngeal carcinoma (NPC) in some malignancy endemic regions in South-East Asia. LMP1 gene is one of the EBV latent genes, which encodes a latent membrane protein. LMP1 gene is thought to be a classical oncogene since it morphologically transforms cells in vitro and induces tumors in experimental animals in vivo. LMP1 is one of a few genes which is expressed in NPC tissues. It was first shown that C-terminus of LMP1 gene obtained from NPC patients in South-East Asia contained a deletion of 30 base pairs (bp). However, this deleted LMP1 gene was then found in the EBV isolates persisting among healthy virus carriers and patients with other EBV-associated abnormalities from both NPC endemic and non-endemic regions. The aim of this investigation was to accomplish a molecular biological analysis of EBV LMP1 genes obtained from Russian NPC patients. To this end, the authors isolated and sequenced the LMP1 clones amplified from the tumor tissues from 7 NPC patients at the N. N. Blokhin Russian Cancer Research Center and primary blood lymphocytes (PBL) from 6 healthy donors. As a result, the authors could not find the deletion of the above-mentioned 30 bp in NPC LMP1 clones, but could in one healthy donor (PBL-2). A functional analysis revealed no significant differences between LMP1 variants with or without 30 bp deletion in their capacity to activate NF kappa B and jun/AP-1 transcription factors. Nevertheless, Russian NPC-derived LMP1 variants as compared with those from PBLs featured some specific amino acid exchanges. These data indicate that the 30 bp deletion of LMP1 gene is not a factor that predisposes to NPC in Russia.

[The cytotoxicity of Chamaenerium angustifolium (L.) Scop. and Hippophae rhamnoides L. tannins and their effect on mitochondrial respiration]. / Tsitotoksichnost' tanninov Chamaenerium angustifolium (L.) Scop. i Hippophae rhamnodies L. i ikh vliianie na dykhanie mitokhondrii.

The cytotoxic activity of complexes of hydrolysable tannins of Chamaenerium angustifolium L. Scop. and Hippophae rhamnoides L. was compared with that of the antineoplastic drugs vinoblastin (VLB), methotrexate (MT), and 5-fluorouracil (5-FU). The tannins yield to VLB and MT in activity but resemble 5-Fu in their active concentration. They inhibited succinate oxidation by the rat liver mitochondria and their cytotoxicity was displayed in much lower concentrations than their inhibitory effect on mitochondrial respiration. It is concluded that tannins inhibit the respiratory chain at the third point of conjugation in the transfer of electrons from cytochrome c to oxygen.

[Bladder foreign body in a 4-year-old girl]. / Inordnoe telo mochevogo puzyria u devochki 4 let.

The specific feature of this case presented is the prolonged clinical manifestations of cystitis despite long-term and diversified antibacterial therapy. Repeated ultrasonography was justifiable in this cases since it could reveal a cause of protracted cystitis. Thus, in the young child long-term dysuria and urinary infection may be caused by a bladder foreign body.

[Current principles in the organization of emergency surgical care in a large city]. / Sovremennye printipy organizatsii ékstrennoi khirurgicheskoi pomoshchi v usloviiakh krupnogo goroda.

The specific character of emergency surgical care requires a concentration of highly skilled specialists of various profiles on the basis of multi-type hospitals and using expensive modern, highly informative and less invasive methods of diagnosis and treatment. The using of multi-type hospitals for emergency medical care will allow the intensification of treatment, wide application of less invasive technologies that will result in the appearance of incentives and conditions to shorten the number of bed-days, restriction of groundless hospitalization and to improve the tariff politics in the system of compulsory medical insurance.

[Croupous pneumonia: current problems and means for their resolution]. / Krupoznaia pnevmoniia: aktual'nye problemy i puti ikh resheniia.

Croupous pneumonia makes up to 7-8% of all pneumonia cases in different regions of the country. 83 lethal outcomes have been studied. In 46 cases pneumonia was primary illness and the direct cause of death. In case a pneumonia is diagnosed an urgent hospitalization and penicillin treatment (maximum effect on pneumococcus is ensured with 1.8-2.4 million units per day) are necessary. For the prevention of acute cardiovascular insufficiency camphor is prescribed for 2-3 days. Mucolytic preparations and--after normalization of temperature--physiotherapeutic methods and therapeutic exercises are used for treatment. In 25-46.6% of lethal cases pneumonia is not diagnosed in their lifetime. Late hospitalization influencing illness's outcome takes place in 73% of cases.

[Functional furosemide loading test. Practical use in children with kidney diseases]. / Funktsional'naia nagruzochnaia proba s furosemidom. Prakticheskoe ispol'zovanie u detei s zabolevaniiami pochek.

Diuretic and aciduretic reactions were compared in healthy children and children with various renal diseases using furosemide loading test. Diuresis, urinary pH, urinary excretion of titered acids and ammonium, and ammonium coefficient were evaluated in healthy controls, patients with chronic and acute renal insufficiency, convalescents after acute renal insufficiency and acute postinfection glomerulonephritis, patients with chronic pyelonephritis, interstitial nephritis, lipoid nephrosis, hematuric chronic glomerulonephritis, and patients with a solitary kidney. Diuresis, urinary pH, ammonium excretion, and ammonium coefficient are proposed as the main test parameters. Patients with the distal tubular acidosis syndrome formed a special group by the results of urinary pH measurements during the third hour of furosemide action. The test helps evaluate the severity of disease and predict its course.