[Polymorphisms of genesencoding enzymes of the xenobiotic detoxification system and the risk of infectious endocarditis].

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.

[Association of leptin and total immunoglobulin E in obese patients].

We measured by the immunoenzyme assay serum levels of total IgE and leptin in 17 men and 95 women with non-alcoholic fatty liver diseases (NAFLD) and in 57 men and 25 women with alcoholic liver disease (ALD) in comparison with 454 control men and 74 women without hepatic pathology. It was shown that the total serum IgE level in patients with ALD (229.5 +/- 31.0 IU/l) is on the average twice that in NAFLD and control patients (89.7 +/- 15.0 and 96.2 +/- 16.0 IU/l respectively). The IgE level in patients with NAFLD is related to BMI and waist circumference (WC). Leptin levels in patients with NAFLD andALD are higher than in control and correlate with obesity signs in all three groups. They correlate with the IgE level and reach the maximum value at a concentration of total IgE over 100 IU/l in men with NAFLD and WC >94 and in women with BMI = >30.0 kg/m2 and WC >80 cm. Positive correlation between IgE, leptin level and obesity signs in men and women with NAFLD suggests that leptin may be a link between obesity, hepatosteatosis, and atopic diseases.

[Chronic inflammatory and dystrophic diseases of the eye anterior segment and their association with genetic polymorphisms in workers of metallurgic industry].

The ophthalmologic investigation of workers of the two metallurgical enterprises has shown that 1045 persons (55%) from 1911 observed workers suffer chronic diseases of a forward piece of eyes. Chronic inflammatory diseases (blepharitis, conjunctivitis and blepharoconjunctivitis) are found at 28,9% of them, and dystrophic diseases (pinguecula/pterygium)--at 25,8%. Among metallurgists (1801 persons) ophthalmopathy was found in 2, 2 times more often than at persons in control group (110 observed engineers and managers). Two polymorphisms of cytochrome P450 1A1 (CYP1A1) and P-450 2E1 (CYP2E1) genes were defined in 91 workers, by the method of allele-specific polymerase chain reaction. It is revealed that CYP1A1 Ile462Val polymorphism associates with pinguecula/pterygium, raising risk of their development almost in 3 times, unlike CYP 2E1 -1293G/C polymorphism. Development of chronic inflammatory diseases is not connected with tested polymorphisms.

[Serum lactoferrin levels in children with viral hepatitis A].

Serum lactoferrin levels were studied in 79 healthy children and 80 children with viral hepatitis A in the Republic of Tyva. No statistically significant age- and gender-related differences were found in the healthy children. In viral hepatitis A, the level of the protein was shown to decrease with disease severity and to return to the normal values after 6 months.

[Alpha-2-macroglobulin ligands and their biotransport mechanisms].

Alpha-2-macroglobulin (MG) is a high-molecular weight glycoprotein that possesses a wide range of regulatory functions. Earlier it has been shown that covalent binding of MG with proteinases results in conformational transformation of MG, which enables MG to transport some additional types of cytokines linked by noncovalent interactions. The results of our study have demonstrated that the range of proteins, with the ability for additional binding with transformed MG is variable and comprises IgG, IgA, IgM, albumin, both types of lipoprotein chain, plasmin, some cytokines and even pregnancy associated alpha-2-glycoprotein (structured MG homolog). The major ligands are found to be albumin, IgG, plasmin and, to a lesser degree, lipoproteins. MG interactions with both acidic and low-alkaline proteinases contribute to neutralization of total charge of the formed complex at neutral pH, typical for internal fluids of the organism, and that the addition of low-density lipoprotein receptor-related protein (LRP) increases the amount of electroneutral complexes at pH 7.4. We suppose, that this mechanism enables the transformed MG (or may be its complex with other regulatory proteins) to rapidly precipitate rapidly on cellular surface and then, after binding with LRP and secondary neutralization of the total charge under physiological pH conditions, to pass through cellular membrane and to realize its own regulatory functions.

[Level of lactoferrin in serum and cerebrospinal fluid of patients with meningitis].

Study showed 9-fold increase of concentration of lactoferrin (LF) in serum of patients with bacterial meningitis (BM) compared with normal concentration and 5-fold increase of LF concentration in patients with aseptic meningitis (AM). Level of LF in cerebrospinal fluid (CSF) of patients with BM and AM was 200-fold and 22-fold higher than in control group respectively. In 71% of patients with AM concentration of protein in CSF did not exceed minimal level observed in patients with BM. Level of LF in serum and CSF during treatment statistically significantly decreased. Concentration of LF (the latter is marker of neutrophilic granulocytes activation) can be used as a characteristic of acuteness and intensity of inflammatory process in central nervous system, whereas detection of LF in CSF--as additional criterion in differential diagnostics between bacterial and viral meningitis. Furthermore, repeated measurement of LF level can be useful for monitoring of disease course and assessment of effect of treatment.

[Development of acute exudative inflammation in rats upon perftoran infusion].

The effect of the perftoran--a blood replacing emulsion with multifunctional properties--on the biochemical parameters of blood serum has been studied in rats with acute exudative inflammation. It is established, that perfloran does not influence the adaptive biochemical reactions on early terms of inflammation development. At the same time, perftoran essentially reduces exudate volume, however this effect is short-time upon single infusion of the preparation.

[Specific reactions of polyfunctional proteins of the family of macroglobulins and lactoferrin with receptors and ligands in the protection of the body from pathogens].

The reactions of polyfunctional proteins alpha2-macroglobulin (MG) and lactoferrin (LF) lipoprotein-receptor protein (LRP) and different ligands (antibodies and hydrolases) for ascertaining the mechanisms of their interaction and the probable role of MG and LF in the neutralization of bacterial pathogens were under study. The binding of MG and LF with ligands, irrespective of their nature, was shown to lead to the neutralization of the complex thus formed. This mechanism of neutralization in reaction of LF with ligands was supposedly due to the antibacterial properties of this protein: multiple reactions of LF with receptor sites on the surface of pathogens neutralized the charge of the latter and facilitated phagocytosis. The interaction of LRP of immunocompetent cells with MG, in the presence of additional binding sites on its surface, made it possible for MG to effectively bind and present even heretofore unknown pathogens in the presence of hydrolases on their surface.

Effect of perftoran on macroglobulin content in the plasma and peritoneal exudate of rats with acute exudative inflammation (peritonitis).

The effect of blood substitute perftoran on the content of alpha(1)- and alpha(2)-macroglobulins in the plasma and exudate was studied in rats with acute exudative inflammation. After intravenous injection of perftoran macroglobulin content increased in the plasma, but remained unchanged in the peritoneal fluid.

[Lactoferrin and its role in the pathogenesis of tick-borne encephalitis]. / Laktoferrin i ego diagnosticheskaia rol' pri kleshchevom éntsefalite.

The content of lactoferrin (LF) was studied in the liquor and blood of patients with tick-borne encephalitis (TBE) of the meningeal and focal types; additionally, the information density of the discussed parameter was assessed for evaluating the severity and degree of the inflammation process in the central nervous system (CNS). The LF level was determined in liquor of 37 samples obtained from TBE patients (main group) and of 10 persons with osteochondrosis (controls); it was also determined in the serum taken from 21 TBE patients and from 40 healthy donors by using the immune-enzyme analysis. The LF concentration in TBE patients was found to exceed the normal value by 1.5-3 times during the whole observation period. As for the liquor, it was high, by the onset of the disease, by more than 20 times, however, after the 7th day it was higher 6-fold. A direct dependence of a concentration of the studied protein on a form and severity of the disease was established. The LF level in the liquor of TBE patients alongside with clinical signs can be an objective indicator of a severity and activity of the inflammation process in the CNS; it can also be a criteria of how much the conducted therapy effective is.

[Permeability of the blood-brain barrier in severe craniocerebral trauma]. / O pronitsaemosti gematoéntsefalicheskogo bar'era pri tiazheloi cherepno-mozgovoi travme.

Permeability of the blood-brain barrier was studied by comparing the molar concentrations of albumin and alpha 2-macroglobulin in the spinal fluid and blood of patients with severe brain injury. If the outcome was good, the selective permeability of the barrier was shown to be fully retained, which meant that its regulatory and protective functions remained normal. If the outcome was poor, the selective permeability changed to a greater extent and the alterations found suggested that the regulatory function of the barrier was preserved with simultaneous loss of its protective properties. More marked changes in the function of blood-brain barrier and in the protein composition of spinal fluid occurred with simultaneously elevated intracranial pressure.

[The possible role of alpha 2-macroglobulin in regulating the immune components of the brain in tick-borne encephalitis]. / Vozmozhnaia rol' al'fa 2-makroglobulina v reguliatsii immunnykh komponentov mozga pri kleshchevom éntsefalite.

In tick-borne encephalitis certain immunopathological reactions develop in the tissues of the central nervous system; alpha 2-macroglobulin may serve as the marker of the activity of these reactions. The dynamic study of liquor taken from 16 patients with the meningeal and focal forms of tick-borne encephalitis (TBE), 8 patients with severe craniocerebral traumas accompanied by meningitis and 10 patients with osteochondrosis was made. As revealed in this study, in TBE patients the level of alpha 2-macroglobulin increases 3.5-fold and remains stable during the acute period of the disease.

[The permeability of the hemato-encephalic barrier and the proteolytic potential of the cerebrospinal fluid in severe craniocerebral trauma]. / O pronitsaemosti gematoéntsefalicheskogo bar'era i proteoliticheskom potentsiale likvora pri tiazheloi cherepno-mozgovoi travme.

To study blood-brain barrier permeability and proteolytic changes in in patients with severe brain injury and to evaluate their impact on its course and outcome, the concentrations of albumin, plasminogen (plasmin), alpha 2-macroglobulin, alpha 2-antiplasmin, and alpha 1-antitrypsin were examined in 58 victims by enzyme immunoassay. The control group comprised 20 patients examined for lumbar discal hernia. The studies indicate that early severe brain injury showed blood-brain barrier dysfunction whose severity can be detected by the spinal fluid levels of albumin, plasminogen, and alpha 2-macroglobulin. Proteolytic changes in spinal fluid are determined by its albumin, plasminogen (plasmin), alpha 2-macroglobulin, alpha 2-antiplasmin, and alpha 1-antitrypsin concentrations and affect the development of secondary brain lesion and they are of practical value.

[The content of the protein markers of hemato-encephalic barrier permeability in the cerebrospinal fluid in severe craniocerebral trauma]. / Soderzhanie belkov--markerov pronitsaemosti gematoéntsefalicheskogo bar'era v spinnomozgovoi zhidkosti pri tiazheloi cherepno-mozgovoi travme.

The CSF levels of albumin, alpha 2-microglobulin and IgG were studied in patients with severe brain injury. Elevated CSF levels of albumin and alpha 2-microglobulin were found in more severe patients. The level of IgG level was within the normal range. Endogenic protease-bound alpha 2-microglobulin may cause secondary cerebral tissue lesion, by closing the vicious circle.

[Immunoenzyme method of lactoferrin analysis]. / Immunofermentnyi metod opredeleniia laktoferrina.

The authors propose a highly effective method for isolation of lactoferrin from female colostrum. Lactoferrin is measured by the sandwich enzyme immunoassay. Its concentrations in the serum, urine, amniotic and cerebrospinal fluid in health are measured. The advantages of the method for lactoferrin purification and the practical significance of this protein are discussed.

[Marker proteins in cerebrospinal fluid of patients with grave craniocerebral injury]. / Soderzhanie belkov-markerov v spinnomozgovoi zhidkosti pri tiazheloi cherepno-mozgovoi travme.

The permeability of the blood-brain barrier for the cerebrospinal fluid marker proteins has been assessed in patients with grave craniocerebral injuries. The content of albumin and alpha 2-macroglobulin in the survivors decreased with time and by day 7 after the injury was virtually normal. In patients who died the content of these proteins was reliably increased starting from day 1. By day 7 the content of albumin in the cerebrospinal fluid approached the norm in this group, whereas the content of alpha 2-macroglobulin remained increased. The level of IgG surpassed the normal value on day 1 only in the patients who died, and later it did not differ from the norm in both groups.

Immunoregulatory Properties of alpha(2)-Macroglobulin.

Native and modified with ammonium ions alpha(2)-macroglobulin forms exhibit similar abilities to influence proliferative activity and secretion of immunoglobulins in cultures of human blood mononuclear cells in vitro. Effects of modified with ammonium ions alpha(2)-macroglobulin were more significant than those of native alpha(2)-macroglobulin. Revealed properties of native alpha(2)-macroglobulin could be conditioned by a partial modification of its structure with endogenous proteinases or cytokines, some of which were shown to be common affinants for both forms.

[A comparative study of pregnancy-associated protein A and its analogs in animals]. / Sravnitel'noe izuchenie assotsiirovannogo s beremennost'iu proteina A i ego analogov u zhivotnykh.

Glycoproteins similar in composition, structure, and functions were isolated from the blood serum of pregnant women, cows, dogs, and rats. They consist of four identical subunits, which form dimers due to covalent bonds, while dimers form tetramers due to hydrogen bonds. All these proteins are non-specific inhibitors of proteases and bind these enzymes in the same way as alpha-macroglobulins do, by capture in a "trap". Furthermore, they are capable of binding and transporting various cytokines. The results obtained indicate that these proteins belong to the family of macroglobulins.

Changes in tissue distribution of rat alpha 1-macroglobulin and pregnancy-associated alpha 1-glycoprotein after inflammatory injury.

Antiserum against rat alpha 1-macroglobulin (alpha 1MG) was produced in rabbits. Antiserum against rat pregnancy-associated alpha 1-glycoprotein (PAG) was obtained by immunization with a partly purified PAG preparation and absorption of the serum with male rat serum. Acute inflammation was produced in non-pregnant female rats by a single intramuscular injection of turpentine. The concentrations of both macroglobulins in the serum and in tissue extracts were measured by rocket immunoelectrophoresis at various times up to 7 days after injury. Inflammation produced in the rats resulted in moderately elevated serum levels of these proteins soon after injury. At first, alpha 1MG levels in a number of tissues (heart, lung, kidney, spleen, pancreas, uterus and ovary) were depressed markedly; they then stabilized. The elevated serum concentrations of alpha 1MG remained unchanged during inflammation. The store of PAG in the tissues was rapidly depleted and its serum level decreased to a normal value 7 days after injury. Our findings indicate that alpha 1MG plays a more important role in maintenance of the proteinase inhibitory potential in the rat than does PAG.

[A comparative study of the physicochemical and antigenic properties of human and animal albumins]. / Sravnitel'noe izuchenie fiziko-khimicheskikh i antigennykh svoistv al'buminov cheloveka i zhivotnykh.

Studies have been made on physico-chemical and antigenic properties of albumins from man, mammals, birds, insects, amphibians, worms, fishes and crustaceans. It was found that all the animals contain structurally identical proteins with similar physico-chemical properties. At the same time, the level of antigenic identity of the proteins decreases in the following order: type, genus, family, species.