[Efficacy and safety of sampeginterferon ß-1a in the treatment of relapsing remitting multiple sclerosis: results of 52 weeks of therapy in a randomized, double-blind clinical trial]. / Effektivnost' i bezopasnost' sampeginterferona ß-1a dlya lecheniya remittiruyushchego rasseyannogo skleroza: rezul'taty 52-nedel'nogo randomizirovannogo dvoinogo slepogo klinicheskogo issledovaniya.

OBJECTIVE: To evaluate the efficacy and safety of samPEG-IFN-ß1a 180 µg and 240 µg administered once every 2 weeks for the treatment of relapsing remitting multiple sclerosis (RRMS) compared to placebo and low dose interferon beta-1a (LIB) 30 µg administered once weekly. The primary endpoint after 52 weeks of therapy was the time to first relapse, the hypotheses of non-inferiority and superiority to LIB were tested. MATERIAL AND METHODS: This international, multicenter, double blind, comparative, placebo-controlled clinical study enrolled 399 patients with the diagnosis of RRMS, randomized in 4 groups: samPEG-IFN-ß1a180 µg (n=114), samPEG-IFN-ß1a 240 µg (n=114), LIB (n=114) and placebo (n=57). Placebo group patients participated in the study for 20 weeks. After 52 weeks of therapy and 4 weeks of follow-up, LIB group patients completed their participation in the study, patients from PEG-IFN-ß1a groups continued to receive therapy until week 100 inclusive. The article presents the results of an analysis conducted after the end of 52 weeks of a double-blind, comparative, randomized, placebo-controlled clinical trial. RESULTS: Final analysis of the efficacy and safety was performed after 52 weeks of study. Main statistical hypothesis testing proved that both doses of samPEG-IFN-ß1a were equally effective when compared to LIB by the primary endpoint - «Time to first relapse¼. Due to detection of statistically significant differences in the primary endpoint between the study drug and the reference drug, indicating a greater efficacy of the study drug, an additional testing was carried out and the hypothesis of superiority of samPEG-IFN-ß1a at a dose of 240 µg over the reference LIB was proved. Evaluation of the dynamics of certain key parameters of magnetic resonance imaging (MRI) of the brain and clinical outcomes demonstrated a positive effect of samPEG-IFN-ß1a therapy in the form of decreased activity of the demyelinating process in the brain and reduce the number of relapses. The proportion of patients without new T2 lesions after 52 weeks was 87.6% and 90.4% in 180 µg and 240 µg samPEG-IFN-ß1a groups, versus 72.6% in the LIB group (p=0.0199 and p=0.0033). No progression of multiple sclerosis was shown based on EDSS scale evaluation. During the study, the most common adverse reactions were flu-like symptoms and injection site reactions. CONCLUSION: The new drug samPEG-IFN-ß1a is an effective and safe agent for relapsing remitting multiple sclerosis treatment, while having an advantage over other low-dose interferons in the form of reduced frequency of intramuscular injections.

[Surgical and conservative treatment of patients with non-traumatic intracerebral hematoma: pros and cons]. / Khirurgicheskoe i konservativnoe lechenie patsientov s netravmaticheskoi vnutrimozgovoi gematomoi: za i protiv.

BACKGROUND: The risk and benefits of early neurosurgical intervention in patients with non-traumatic intracerebral hematoma (NICH) are still unclear. OBJECTIVE: To evaluate an effectiveness of early surgery in patients with NICH compared to primary conservative therapy. MATERIAL AND METHODS: There were 115 patients with indications for surgery. The indications were supratentorial NICH over 30 cm3 and GCS score >7 points. All patients were divided into 2 groups: the main group (n=59) - NICH removal within 24 hours; the control group (n=56) - conservative treatment only. Both groups were comparable by the main clinical, demographic and neuroimaging characteristics. We analyzed survival rates and functional status using Glasgow outcome scale extended (GOSE) 6 months later. RESULTS: Median survival in the main group was 71 days vs. 11 days in the control group (p<0.05); cumulative 6-month survival - 46% and 34%, respectively (p>0.05). Surgical treatment resulted higher number of patients with severe (13% vs. 5%) and moderate disability (29% vs. 23%). There were 2% of patients with good recovery in the group of surgical treatment and 4% of patients after conservative management. However, between-group differences were not significant (p>0.05). CONCLUSION: Early surgical evacuation of non-traumatic intracerebral hematoma is accompanied by less early postoperative mortality. There were no significant between-group differences in functional outcomes and survival rates after 6 months.

[The new pegylated interferon beta-1a (sampeginterferon beta-1a, BCD-054) in the treatment of remitting multiple sclerosis]. / Novyi pegilirovannyi interferon beta-1a (sampéginterferon beta-1a, BCD-054) v terapii remittiruiushchego rasseiannogo skleroza.

AIM: To evaluate the efficacy and safety of BCD 054 180 µg and 240 µg administered once every 2 weeks for the treatment of remitting multiple sclerosis compared to placebo and low dose interferon beta-1a (LIB) 30 µg administered once weekly. Results of a 20 week blinded interim analysis from a double blind, comparative, randomised, placebo-controlled clinical study are included. MATERIAL AND METHODS: This multinational, multicentre, double blind, comparative, placebo-controlled study enrolled 399 patients with the diagnosis of remitting multiple sclerosis: 114 patients in the sampeginterferon beta 1a and LIB groups each and 57 patients in the placebo group. To ensure the objectivity of data, the study protocol includes a blinded interim analysis to demonstrate the superiority of BCD 054 over placebo based on the number of combined unique active lesions (CUA) on MRI scans after 20 weeks of treatment. RESULTS AND CONCLUSION: An integrated analysis of the efficacy, safety, pharmacokinetics, and pharmacodynamics was performed after 20 weeks of study. Mean CUA per scan was lower in the active treatment groups compared to placebo: 0,986±2,046, 0,619±1,055, 0,665±1,165, 1,673±2,376 (groups 1, 2, 3 and placebo group, respectively). The data for CUA per scan demonstrated the superiority of both BCD 054 180 µg and 240 µg over placebo. Patients receiving active treatment had fewer new and/or enlarging lesions after 20 weeks of treatment. The proportion of patients without new T2-weighted lesions was 74,3%, 86,7%, and 78,1% in groups 1, 2, and 3 compared to 64,9% in the placebo group. Manifestations of flu-like syndrome that is expected for interferon treatment were observed with the same incidence in all the active treatment groups. Its severity, duration or the need for symptomatic treatment did not appear to depend on the type of interferon used.

[Bio-antioxidant activity of 3,5-di-tert-butylpyrocatechol and its influence on hypoxia, inflammation, pain and burns]. / Bioantioksidantnaia aktivnost' 3,5-di-tret-butilpirokatekhina i ego vliianie na gipoksiiu, vospalitel'nyí protsess, bolevoí sindrom i ozhogi.

The bioantioxidant activity of the synthesized by us on the base of the diatomic phenol compound--3,5-di-t-butylpyrocatechol--has been studied. It was shown that this substance exhibits more pronounced antioxidant properties than tocopherol on the lipid peroxidation process in the rat brain homogenate appears in concentrations right up to 10(-8)-10(-7) M. Antioxidant effect of 3,5-di-t-butylpyrocatechol protecting action correlation has been found in the simulation of such pathological organism states as hypoxia, inflammation, burn, pain. All above mentioned results confirms the expedience of search for new drugs based on diatomic phenols.

[Effect of ischemic damage factors on lipid peroxidation in rat brain synaptosomes]. / Vliianie faktorov ishemicheskogo povrezhdeniia na perekisnoe okislenie lipidov v sinaptosomakh mozga krys.

Accumulation of TBA-reactive substances after a 40 min incubation of rat brain synaptosomes at 37 degrees C was analysed. A lowering of pH to 6.5-5.5 or arachidonic acid (0.1-1.0 mM) increased lipid peroxidation which was blocked by antioxidants. Acidosis (pH 6.0) and arachidonic acid used in combination had a strong synergic effect. Depolarisation of plasma membranes or intrasynaptosomal mitochondria were without influence on lipid peroxidation at neutral or acid pH. The results support a leading role of acidosis and phospholipases in stimulation of peroxidation under ischaemia.

[Effect of acidosis on membrane potential and calcium transport in rat brain synaptosomes]. / Vliianie atsidoza na membrannyi potentsial i transport kal'tsiia v sinaptosomakh mozga krys.

The influence of acidosis on the transmembrane potential, sodium pump and membranous systems of calcium transport was studied on isolated presynaptic nerve terminals (synaptosomes) from rat brain. It is established that acidic shift causes a decrease of membrane potential, a large inhibition of the sodium pump (by three times at pH 6.0). All the systems controlling both inward- and outward-directed calcium fluxes are partially blocked by low pH. At pH 6.0 the basal influx and calcium pump are reduced two-fold while the voltage-sensitive calcium channels and Na+/Ca2+ exchanger are inhibited by three and four to five times, respectively. We have no found any evidence of acidosis-induced net flux of calcium directed inwards.

Swelling-induced activation of Na+,K+,2Cl- cotransport in C6 glioma cells: kinetic properties and intracellular signalling mechanisms.

Swelling of C6 glioma cells in hypotonic medium (180 mOsm) results in two- to three-fold activation of K+ (86Rb+) influx suppressed by 10 microM bumetanide. Bumetanide-sensitive transport of 86Rb+ is dependent on extracellular K+, Na+ and Cl- both in iso-osmotic conditions and under hypo-osmotic shock, supporting the notion that it is mediated by Na+,K+,2Cl- cotransport. Inhibitors of protein kinase C (10 microM polymyxin B and l microM staurosporine) had no significant effect on basal cotransport but reduced its hypotonic stimulation by 70-80%. Similar results were obtained with calmodulin antagonist R24571 (10 microM), indicating Ca2+/calmodulin-dependence of the process. Influence of polymyxin B and R24571 was not additive. Swelling-activated Na+,K+,2Cl- cotransport was also suppressed by protein kinase C activator PMA (l microM). By contrast, preincubation of cells with inhibitors of protein phosphatases (100 microM vanadate, 5 mM fluoride and 0.5 microM okadaic acid) activated greatly the bumetanide-sensitive 86Rb+ uptake in isotonic conditions, while a subsequent hypotonic swelling led to smaller or no increment. These results indicate the involvement of Ca2+/calmodulin-dependent staurosporine/polymyxin B-sensitive protein kinase other than protein kinase C in swelling-induced activation of Na+,K+,2Cl- cotransport in glial cells.

[Fibrinolytic activity of the lacrimal fluid in disordered choroid circulation in patients with arterial hypertension]. / Fibrinoliticheskaia aktivnost' sleznoi zhidkosti pri narusheniiakh khoroidal'nogo krovoobrashcheniia u bol'nykh s arterial'noi gipertoniei.

Fluorescent angiographic examination of the choroid and retinal circulation in 43 patients with arterial hypertension of different origin without signs of hypertensive retinopathy with low and normal values of the fibrinolytic activity of the lacrimal fluid (FALF) revealed a correlation between disorders of the choroid circulation (ischemic zones, delayed time of contrast staining of the choroid) and reduction of FALF. The results indicate that a reduction of FALF may be regarded as a prerequisite for the development of circulatory disorders in the choroid.

[Synthesis and properties of membrane-addressed antioxidants based on phosphorylated pyrocatechols]. / Sintez i svoistva membranoadresovannykh antioksidantov na osnove fosforilirovannykh pirokatekhinov.

Amphiphilic membrane-addressed antioxidants differing in their hydrophobic-hydrophilic balance, 3,5-di-tert-butyl-2-hydroxyphenyl phosphate, (3,5-di-tert-butyl-2-hydroxyphenyl)hexadecyl phosphate, and (3,5-di-tert-butyl-2-hydroxyphenyl)-5-cholesten-3 beta-yl phosphate, were synthesized starting from 3,5-di-tert-butyl-o-quinone. Even at 10(-8) M concentration, 3,5-di-tert-butyl-2-hydroxyphenyl phosphate and (3,5-di-tert-butyl-2-hydroxyphenyl)hexadecyl phosphate inhibit formation of malonic aldehyde during peroxidation of lipids from rat brain homogenate initiated with a Fe(2+)-ascorbate system. At 10(-4) M and higher concentrations of antioxidants in the brain homogenate, the formation of malonic aldehyde is inhibited more efficiently than with tocopherol at the same concentrations.

[The dynamics of the individual profiles of brain asymmetry in patients with craniocerebral trauma under the influence of emoxipin treatment]. / Dinamika individual'nykh profilei asimmetrii mozga u bol'nykh s cherepno-mozgovoi travmoi pod vliianiem lecheniia émoksipinom.

The authors studied the effect of the drug emoxypin on the brain functional asymmetry (A) in 36 patients with craniocerebral trauma attended by occurrence of focal traumatic injuries (FTI) to the brain (experimental group). The control group consisted of 61 patients who received the traditional intensive therapy for FTI (isolated brain contusion of moderate and severe degree, intracerebral hematomas measuring 30-50 cm3 in volume in the contusion focus). Favorable changes of the brain FA indices in the individual asymmetry profiles were noted, respectively, in 76.7% and 40.9% of patients given and not given emoxypin. Complete normalization of brain FA indices by the 25th-30th day after the beginning of treatment was recorded in 60.9% of patients in the control group and in 37% of those in the experimental group. The dynamics of individual asymmetry profiles in patients with FTI provides evidence that emoxypin improves the attention, mental efficiency, memory capacity, and selectivity of mnemonic processes.

[Lipid peroxidation in the blood and spinal fluid of patients with craniocerebral injuries]. / Perekisnoe okislenie lipidov v krovi i spinnomozgovoi zhidkosti u bol'nykh s cherepno-mozgovoi travmoi.

The content of the products of lipid peroxide oxidation in the plasma of blood flowing from the brain was higher in patients with moderate and severe craniocerebral injury than in patients with no marked functional and metabolic disorders. The concentration of these products in the cerebrospinal fluid was still higher. In patients with severe craniocerebral injury there was also an increase in the content of free fatty acids in blood flowing from the brain and in the content of ferrous iron ions in the cerebrospinal fluid. The intensification of the processes of lipid peroxide oxidation in the brain may play an essential role in determining the severity of the traumatic damage.