Rat macroglobulins were determined in blood sera and extracts of tissues of intact rats and rats with Walker carcinoma by rocket immunoelectrophoresis. The serum levels of alpha1-macroglobulin (alpha1MG) alpha2-macroglobulin (alpha2MG) and pregnancy-associated alpha1-glycoprotein (alpha1PAG) were 1.86 +/- 0.07 mg/ml, 0.12 +/- 0. 02 mg/ml and 18.32 +/- 4.07 AU/ml respectively in control rats. Maximum concentrations of alpha1MG were found in heart, lung and spleen and lesser quantities were in liver and thymus, while alpha2MG and alpha1PAG were not found at all in tissue extracts from control rats. Serum alpha2MG and alpha1PAG concentrations increased more than 30-fold in tumour-bearing rats compared to control animals, while alpha1MG serum concentration was little changed. Increases in all three macroglobulins occurred in the tissues of tumour-bearing rats, particularly alpha1PAG. The tissue concentrations of alpha1MG and alpha2MG were similar and the tissue distribution was also similar with highest concentrations in heart and lung. Considerable quantities of the proteins were found in the tumour and part of peritoneum which made contact with the tumour. Changes in the protein concentrations in serum and tissue extracts of tumour-bearing rats suggest that all members of rat macroglobulin family are disturbed during the development of the Walker carcinoma, though only alpha2MG and alpha1PAG were substantially elevated.

Aim — to study of gene polymorphisms affecting the effectiveness of timolol treatment of primary open-angle glaucoma.Patients and Methods. The study included 39 Russian patients (29 women and 10 men) aged 53 to 89 years old with a diagnosis of primary open-angle glaucoma (POAG). Intraocular pressure (IOP) was measured before the start of therapy and after 2 weeks during treatment. Сoefficient of decrease in IOP was calculated in percentage of its initial level (∆D). Patients were genotyped according to the polymorphic loci MMP1-160insG, MMP12A-82G, TIMP1C536T, ADRB1Arg389Gly, ADRB1Ser49Gly, NAT2Lys268Arg, GSTP1Ile105Val using the corresponding SNP-express reagent kits (NPF Lytech, Moscow).Results. No effect of MMP12A-82G, TIMP1C536T, ADRB1Arg389Gly, NAT2Lys268Arg polymorphisms on efficiency of reduction of IOP under action of thymolol in “best” eyes was revealed. The carriage of a homozygous genotype GSTP1Ile105Ile resulted in the best ophthalmic hypotensive effect of a timolol (∆D ≥ 20 %), which probability was 5.63 times higher in comparison with ∆D < 20 %. In the “worst” eyes, the association of carriage of a combination of wild genotypes GSTP1Ile105Ile×NAT2Lys268Lys with the best response of patients to timolol was revealed. The ophthalmic hypotensive effect of 10 ≤ ∆D < 20 % in such carriers was more than 11 times more likely than ∆D < 10 %.Conclusion. The carriage of the wild genotype GSTP1Ile105Ile determines the best ophthalmic hypotensive effect of timolol and can be a prognostic marker for the effective treatment of patients with POAG. The combination of wild genotypes GSTP1Ile105Ile×NAT2Lys268Lys can contribute to the better therapeutic effect of timolol, and mutant ones can prevent it.

No abstract

Infectioue endocarditis (IE) is frequently associated with the use of narcotic drugs, glucocorticosteroids, and cytostatics that are metabolized in the body by enzymes of the xenobiotic detoxification system (XDS). This work was aimed at elucidating association between IE and mononucleotide polymorphisms of genes encoding XDS enzymes. 46 IE patients and 114 subjects without cardiovascular diseases (controls) underwent genotyping for polymorphic loci of cytochrome P450 1A1 gene I462V (CYP1A1), I105VandA114V gene of glutathione-S-transferase Pi1 (GSTP1) using allele-specific PCR. The study revealed association of CYP1A1 I462VandGSTP1 I105V with IE while IE proved unrelated to GSTP1 A114V polymorphism. Combination of homozygous variant I462I of the CYP1A1 gene and heterozygous variant I105V/ of the GSTP1 gene was associated with the 9-fold increase of the risk of IE in the subjects practicing intravenous druginjections or having congenital and acquired heart failure or implanted valve prostheses. These findings suggest the necessity of further studies on the role of XDS in pathogenesis of IE and other infectious diseases.

Te increase in the prevalence of arterial hypertension (AH) in populations, ineffective treatment, the need for risk stratifcation, prevention, early diagnosis and successful treatment, actualize genomic studies to develop a personalized therapeutic approach to AH. Te review investigates the possible genetically determined mechanisms of the development of hypertension and endothelial dysfunction caused by polymorphism of the genes of endothelial nitric oxide synthase (eNOS) and enzymes of phases I and II of the xenobiotics detoxifcation system. Te probable interaction of both systems under the influence of harmful environmental factors, including tobacco smoking, and in the gestational period is discussed. It is proposed to study AH candidate genes in the xenobiotics detoxifcation system, the carriage of different variants of which can determine the sensitivity or resistance to antihypertensive pharmacotherapy, which can be useful for developing of the personalized tactics of managing patients with AH.

No abstract

Insufficiency of local immunity can play an important role in pathogenesis of sepsis, including septic (acute) infectious endocarditis (IE). The paper presents data on secretory immunoglobulin A (sIgA) contents in blood serum of patients with sepsis (26 women and 32 men), acute (11 women and 23 men) and subacute (7 women and 13 men) IE, depending on localization of the infection site (angiogenic or non-angiogenic), outcome of the disease and carriage of glutathione-S-transferase P1 gene variants (GSTP1Ile105Val). A control group consisted of 25 women and 24 men without hypertension and ischemic heart disease and lacking evidence of focal and systemic infection, was examined. Laboratory studies were performed with еnzyme immunoassay and allele-specific polymerase chain reaction. We have found that, despite large individual variability of serum sIgA concentration in sepsis and infectious endocarditis, the majority of patients had a significant (on average, 4-fold) IgA increase against controls, in both men and women, especially in acute IE (a mean of 5-fold over control values). Subacute infectious endocarditis is associated with lesser sIgA in circulation than acute IE and sepsis, which may be used for early differential diagnosis of these conditions. There were no gender differences in sIgA contents. In sepsis with non-angiogenic source of infection, the sIgA levels were higher than in angiogenic infection. There was no association of sIgA level with survival (mortality), which excludes this index from predictive markers in sepsis and IE. Carriage of heterozygous GSTP1Ile105Val genotype increases the risk of sepsis and IE development, regardless of clinical course, and homozygous genotype GSTP1Ile105Ile is associated with higher contents of circulating immunoglobulin than in carriers of GSTP1Val105Val genotype. Thus, a wide range of individual variability in of circulating sIgA levels in patients with sepsis and infective endocarditis may be connected with location of infection source and genetic factors.

Резюме. Изучали содержание связанных с ОБМ антител (иммунокомплексов ОБМ) в сыворот-ке крови при гестозе различной степени тяжести по сравнению с физиологической беременностью и небеременными женщинами. Концентрацию IgG-антител, связанных с ОБМ, определяли имму-ноферментным методом. Установлено, что у небеременных женщин и при физиологической бере-менности в сыворотке крови находится около 0,05 мкг/мл антител класса IgG, связанных с основ-ным белком миелина. Развитие легкого гестоза сопровождается повышением их сывороточной концентрации в 2-3 раза. Усугубление тяжести гестоза приводит к ее дальнейшему прогрессирую-щему подъему, так что максимальная концентрация комплексов (0,8 мкг/мл) определяется при пре-эклампсии и эклампсии. В постэкламптический период их количество снижается вдвое. Показатель концентрации антител класса IgG, связанных с основным белком миелина, в сыворотке крови при гестозе может использоваться для оценки степени тяжести гестоза и прогноза риска возникновения эклампсии.Ключевые слова: основной белок миелина, иммунокомплексы, беременность. Levchenko V.G., Maltseva N.V., Lykova O.F., Konysheva T.V., Zorina V.N. Contents of serum myelin basiC protein-igG antibodies Complexes in normal preGnanCy and Gestosisabstract. Serum levels of myelin basic protein (MBP)-bound immune complexes were studied in blood sera from women with gestosis, as compared with those in normal pregnancy and non-pregnant woman. The amounts of IgG-MBP complex in blood serum were determined by enzyme immunoassay using isolated anti-МBP-antibodies. The study has shown that about 0.05 mcg of IgG ml of blood serum are associated with myelin basic protein in unpregnant women or in normal pregnancy. Mild gestosis is accompanied by a 2-3-fold increase in MBP immunocomplex concentrations in blood serum. More severe stages of gestosis are characterized by its further rise, thus achieving maximal values of such MBP immune complexes (0.8 mcg/ml) in patients with pre-eclampsia and eclampsia. Their amounts were reduced twice after the periods of eclampsia. Serum levels of MBP-bound IgGs may be used to determine severity of gestosis and to predict a risk of eclampsia in pregnant women. (Med. Immunol., vol. 12, N 1-2, pp 155-160)