[The role of adipose tissue in rheumatoid arthritis].

AIM: To estimate the frequency of obesity in a Russian cohort of patients with early rheumatoid arthritis (RA), determine adipocytokine (adiponectin, leptin) levels and their relation to RA activity. MATERIALS AND METHODS: 47 patients with early RA fulfilling ACR/EULAR(2010) criteria and using no BAID or GC. Mean age 57 [47;62] yr, duration of disease 7 [4;8] yr, median of DAS28 5.9 [5.3; 69]. Control group included 30 age-matched healthy donors. The degree of obesity was assessedfrom metabolic syndrome criteria (NCEP/ATPIII, RSSC, WHO); leptin and adiponectin were measured by ELISA, the L/A ratio was calculated. RESULTS: Patients with RA had the same mean BMI but greater waist circumference (WC) and waist/hip ratio than controls (p=0.003 and p = 0.04). Obesity was diagnosed in 63.8 and 40% of the patients in these groups (p=0.04) based on NCEP/ ATPIII criteria and in 65.9 and 40% respectively by WHO criteria. The occurrence of obesity by RSSC criteria was not significantly different (p = 0.9). In patients with RA adiponectin level was higher (p=0.04) while leptin level and L/A ratio lower (p=0.02 and 0.003) than in controls. BMI correlated with ESR, CRB, DAS28, leptin and L/A (p<0.05) in both groups. ESR positively correlated with leptin level andA/L but negatively with adiponectin level (p<0.05). CONCLUSION: The study showed high prevalence ofobesity in patients with early RA and its relation to inflammation. It was associated with increased serum adiponectin level, decreased leptin level and insulin resistance.

[Recurrent thromboses and hemorrhagic complications in patients with antiphospholipid syndrome during therapy with warfarin plus aspirin].

AIM: To estimate the frequency of relapses of thrombotic and hemorrhagic complications during moderately intensive therapy for antiphospholipid syndrome (APS) with warfarin with and without aspirin. SUBJECTS AND METHODS: Eighty-two patients diagnosed as having the antiphospholipid syndrome were examined. Group 1 patients (n = 49) received warfarin alone as an antithrombotic drug; Group 2 patients (n = 33) had a combination therapy with warfarin plus aspirin. The efficiency of therapy was evaluated from the number and rate of recurrences of thromboses and transient ischemic attacks (TIA) and its safety was assessed from the frequency and number of hemorrhages during the study. The genetic variants of cytochrome P450 CYP2C9 were determined in 52 of the 82 patients; mutations in the gene for vitamin K epoxide reductase complex 1 (VCORC1) were revealed in 22 patients. RESULTS: During the follow-up, antithrombotic therapy was ineffective in 18.4 and 36.6% of the Groups 1 and 2 patients, respectively (p = 0.07). The rate of poor outcomes (thromboses and TIA) was 7 and 14.8 cases per 100 person-years, respectively. The first six months of warfarin therapy proved to be most risky for thrombotic events to occur--this period was responsible for 37% of bleedings. Hemorrhagic complications of antithrombotic therapy developed in 46.9 and 60.6% of Groups 1 and 2 patients, respectively (p = 0.26). Major hemorrhages were observed more frequently in the combination (warfarin plus low-dose aspirin) therapy group than in the warfarin monotherapy group. Mutant cytochrome P450 gene variants (CYP2C9*2 and CYP2C9*3) were present in 38.5% of the patients; VCORC1 gene mutations were observed in 27.3%. The number of nasal and gingival hemorrhages was increased in patients with CYP2C9*3 and homozygous VCORC1 gene mutations. CONCLUSION: Moderately intensive warfarin therapy (international normalized ratio 2.0-3.0) could generally reduce the frequency of recurrent thrombotic events by at least 2-fold as compared with that before warfarin administration. The efficiency of using warfarin alone or in combination with aspirin in APS was found to be similar; and its safety was higher during monotherapy therefore it is undesirable to combine warfarin with antiaggregants in real clinical practice. The determination of CYP2C9 and VCORC1 genotypes in patients with APS before warfarin use allows excessive hypocoagulation and related hemorrhages to be avoided.

[Warfarin in the treatment of antiphospholipid syndrome].

AIM: To assess efficacy and safety of warfarin therapy and its combination with low-dose acetylsalicylic acid (ASA) in antiphospholipid syndrome (APS). MATERIAL AND METHODS: The trial enrolled 60 APS patients. They were divided into two groups: group 1 (n = 39) on antithrombotic therapy with warfarin; group 2 (n = 21) on combined therapy with warfarin and ASA. Efficacy of the treatments was assessed by the number and frequency of thrombosis recurrences and transient ischemic attacks (TIA) while safety was evaluated by frequency and number of hemorrhages during the study. Genetic variants of cytochrome P450 (CYP2C9*1, CYP2C9*2 and CYP2C9*3) were studied in 30 patients (25 females, 5 males) with APS. CYP2C9 gene genetic variants were determined by polymerase chain reaction and restrictase analysis. RESULTS: The thrombosis rate was 19.6 per 100 man-day, TIA rate was not less than 8 per 100 man-day, total rate of thrombotic complications (thromboses and TIA) before warfarin individual dose adjustment--27.6 per 100 man-day. Doses of anticoagulant were adjusted and the patients on treatment were followed up for 15.7 months, on the average. For this period thrombosis occurred in 6 cases (7.6 per 100 man-day), TIA also in 6 cases (7.6 per 100 man-day). This corresponded to thrombotic complications rate 15.1 per 100 man-year. Hemorrhages (major and minor) occurred in 19 (48.7%) patients of group 1 and in 13 (61.9%) patients of group 2 (p = 0.33). Total rate of CYP2C9*2 and CYP2C9*3 carriage was 36.7%. The CYP2C9*2 variant was detected in 7 (23.3%) patients, who were all heterozygous carriers. The CYP2C9*3 variant was seen in 4 (13.3%) patients: 3 heterozygous and 1 homozygous. Females of reproductive age with mutations had more frequent menorrhagies than carriers of a wild-type variant. Patients with CYP2C9*3 had also more frequent nasal hemorrhages and gingival bleeding (p = 0.005) compared to carriers of CYP2C9*1 and CYP2C9*2. Episodes of MHO rise > 5.0 in warfarin therapy were observed in 50% carriers of CYP2C9*3 and in none homozygous carriers of CYP2C9*1 (p = 0.024). CYP2C9*3 patients needed lower maintenance doses of warfarin, in CYP2C9*1 and CYP2C9*2 patients anticoagulant doses were comparable. CONCLUSION; Efficacy of warfarin for secondary prophylaxis of thrombosis was found similar to that of warfarin use in combination with low-dose ASA (MHO 2.0-3.0). Safety of monotherapy was higher. Determination of CYP2C9 genotype in APS patients before treatment with oral anticoagulants may help in planning individual policy and in reducing the risk of warfarin overdosage at the start of therapy.

[Optimization of treatment of patients with insulin-dependent diabetes mellitus using multiple injections of insulin]. / Optimizatsiia lecheniia bol'nykh insulinzavisimym sakharnym diabetom s pomoshch'iu mnogorazovykh in''ektsii insulina.

The use of various regimens of multiple insulin injections versus the regimen of a single injection resulted in more stable compensation of diabetes mellitus (glycemia stabilization), a decrease in insulin demand, smoothing over circadian glycemic variations, and correction of hypoglycemia. A choice of the number of injections and the time of administration depended on the type of a diabetic course, individual features of the patient's life style and work.

[Function of the hypothalamo-hypophyseal-thyroid system in juvenile enlargement of the thyroid]. / Funktsional'noe sostoianie gipotalamo-gipofizarno-tireoidnoi sistemy pri iuvenil'nom uvelichenii shchitovidnoi zhelezy.

A study of TTH, T3 and T4 content in the blood serum of adolescents with juvenile thyroid enlargement showed changes which were typical of subclinical hypothyrosis. A conclusion is made about the necessity of a follow-up of children with juvenile thyroid enlargement and administration of pathogenetic therapy with thyroid hormonal drugs.

[Diagnostic problems of autoimmune thyroiditis]. / Voprosy diagnostiki autoimmunnogo tireoidita.

The most informative diagnostic criteria of autoimmune thyroiditis were revealed. A kit of diagnostic tests were offered for each version of autoimmune thyroiditis. The lowest percentage of antibodies against thyroglobulin was demonstrated for the hyperthyroid hypertrophic version of autoimmune thyroiditis, while the highest for its atrophic pattern. Biopsy of the thyroid was found to be the most informative test for autoimmune thyroiditis, provided the result was positive. If the result of puncture biopsy is negative, it is desirable to apply a complex of tests depending on thyroid function and size.

[Effect of the carbon sources and metabolic inhibitors on endopolymethylgalacturonase secretion in Aspergillus foetidus]. / Vliianie istochnikov ugleroda i nekotorykh metabolicheskikh ingibitorov na sekretsiiu éndopolimetilgalakturonazy u Aspergillus foetidus.

The mycelium of Aspergillus foetidus was grown for 48 h, washed off, and used to study the effect of various carbon sources on the synthesis and secretion of endopolymethylgalacturonase (endo-PMG). Sucrose, glucose, glucose-6-phosphate, fructose, pectin and mannitol were shown to favour the enzyme secretion from the mycelium. The enzyme accumulation in the medium was inhibited when such inhibitors of metabolism as sodium azide and fluoride, 2,4-dinitrophenol and N,N'-dicyclohexyl carbodiimide were added, together with glucose, to the phosphate buffer. The secretion of endo-PMG from the mycelium of Aspergillus foetidus is presumed to be an energy-dependent process.

[Content of acid soluble nucleotides in the microscopic fungus Sclerotinia sclerotiorum at different growth stages]. / Soderzhanie kislotorastvorimykh nukleotidov u mikroskopicheskogo griba Sclerotinia sclerotiorum na paznykh fazakh rosta.

Variations in the content of acid soluble nucleotides at different growth stages of the producer of pectolytic enzymes-the fungus Sclerotinia sclerotiorum were measured. The initial growth stage was characterized by an increased content of adenyl nucleotides whose amount decreased by the 48th hour. In the 48-hour mycelium guanyl nucleoside mono- and diphosphates were the major components of the nucleotide pool. Throughout the entire cultivation cytidyl derivatives occurred in trace quantities.