[Stimulation of Research in Biomedicine. Role of Effective Contract].

Background: Analysis of publication activity in the field of biomedicine shows insignificant input of Russia in the world scientific product. This is largely due to the lack of incentives for researchers. Article describes stimulation of researchers in Russia, compares it with foreign models, formulates main shortcomings of support and stimulation of research in Russia and introduces the concept of effective contract. Aims: Development of personnel motivation and stimulation of employees of scientific and research organizations in the field of health. Materials and Methods: As a successful experience the article describes the implementation of effective contract in Veltishev Research and Clinical Institute for Pediatrics where for years remuneration of researchers depended upon their positions without consideration of research results. Effective contract brought significant changes in the traditional system setting new performance and efficiency criteria. New evaluation system took into account publication activity, presentation activity, implementation of research results, raising scientific personnel, thesis work and income-generating activities. Results: Introduction of effective contract already in the second year led to a rise in the number of foreign publications, publications in journals with impact factor of more than 2, the general increase in the number of articles in peer-reviewed journals with impact factor more than 0.3, the growth of the number of articles by 1 researcher, Hirsch index improving both by individual employees and the entire Institute, increase of grant activity and presentation activity at top-rated professional congresses. The growth of publication and presentation activities has been achieved at the reduction of research staff by 23%. From financial viewpoint effective contract resulted in the redistribution of resources in favour of more efficient researchers. Conclusions: The introduction of effective contract and increase of requirements for scientific output did not cause resistance of staff, although demanded certain time for joint development of criteria by scientific community, as well as the development and implementation of soft for continuous assessment of research activity.

[The endogenous intoxication in pathogenesis of nephropathies].

The endogenous intoxication of organism can be a primary cause of changing in content of protein molecules with enhancement of their capacity to adsorb microelements fastening conformation of proteins. Such an alteration add them antigen characteristics conditioning autoimmune damage of tissues, kidneys included. The most frequent syndromes (cases?) ofendogenous intoxication effecting kidneys pathology are presented.

[Ecopathology of the kidneys and individual sensitivity to heavy metal salts]. / Ekopatologiia pochek i individual'naia chuvstvitel'nost' k soliam tiazhelykh metallov.

Investigations performed in the region contaminated with heavy metal salts revealed high prevalence of renal diseases in children. The test for blood polymorphic proteins indicated signs of genetic predisposition to renal damage. Greater occurrence in the population with econephropathy of a rare allele of transferrin C3 may be the cause of enhanced oxidative-radical processes in renal cells. Individual sensitivity of children to heavy metal salts assessed by leukocytolysis and high incidence of somatic mutations to determine T-lymphocyte microclones deficient by HGPRT may help in specification of the affections detected in the regions contaminated with heavy metal salts.

[Nephropathies in a region contaminated by heavy metal salts and the possibilities for therapeutic and prophylactic measures]. / Nefropatii v regione, zagriaznennom soliami tiazhelykh metallov, i vozmozhnosti lechebno-profilakticheskikh meropriiatii.

The study of the population in the region contaminated with heavy metal salts has revealed high incidence of nephropathies even in preschool children manifesting initially in the majority of cases with hematuria. All the patients had the signs of urinary dysembryogenesis and marked membranopathological process. Long-term exposure to even small doses of heavy metals is supposed to cause nephropathy. Urinary disease arose more frequently in those genetically predisposed to renal and urinary tract affections. Because urolithiasis is a frequent result of dismetabolic nephropathy in endemic regions, it is advisable to perform active monitoring of children with environmental nephropathy using membrane-stabilizing measures. Optimal for these purpose could be xidifon. Further studies are needed to elucidate the problem of rapid elimination of heavy metals with chelating agents.

[Viral antigens in kidney biopsies of children with glomerulonephritis]. / Virusnye antigeny v bioptatakh pochechnoi tkani u detei s glomerulonefritom.

A relationship between clinical forms of glomerulonephritis and incidence of viral antigens in renal tissue was revealed: Hepatitis B virus antigens (HBsAg) are more frequently detected in the glomeruli in the patients with nephrotic glomerulonephritis, Herpes simplex antigens are detected in the glomeruli in mixed glomerulonephritis, and cytomegaloviral and Herpes simplex antigens are detected in the epithelium of the proximal canaliculi in patients with hematuric glomerulonephritis. No correlations between the persistence of Herpes simplex type 1, cytomegalovirus, and HBsAg in the renal tissue were detected. HBsAg is detected in the renal tissue mainly in the children without free HBsAg in the blood serum. This may be indicative of an important role of specific immune complexes in the pathogenesis of glomerulonephritis associated with hepatitis B viral infection. The results point to an appreciable contribution of a persistent viral infection to the progress of glomerulonephritis.

[HB viral infection in kidney diseases in children]. / HB-virusnaia infektsiia pri zabolevaniiakh pochek u detei.

A total of 142 children aged 2-15 years with different nephropathies, among them 94 children with glomerulonephritis (GN), 26 children with pyelonephritis and 22 children with oxalate nephropathy, were examined. The diagnosis was histologically confirmed in 36 children. Mesangial proliferative GN was detected in 22 patients and membrane proliferative GN, in 14 children. The presence of the markers of HBV infection (HBsAg, anti-HBs and anti-HBc total immunoglobulins, anti-HBc IgM) was detected in the sera of all patients by the enzyme immunoassay. As the result of this examination, essential changes in the distribution of different markers of HBV infection in children with nephropathies were detected. The combination of HBsAg with anti-HBc IgM proved to be the most characteristic feature of patients with the nephrotic syndrome; this was indicative of active HBV infection, and in patients with the mixed form of GN this combination occurred twice as frequently. The established correlation between the activity of HBV infection and the severity of the course of GN made it possible to suggest the participation of HBV in the pathogenesis of GN. This suggestion was indirectly confirmed by a higher detection rate of HBsAg and anti-HBc IgM in patients with the membrane proliferative form of GN.

[The dynamic production of interferons, interleukins and arachidonic acid metabolites by the blood cells of children with glomerulonephritis associated with HB virus infection while treated with reaferon]. / Dinamika produktsii interferonov, interleikinov i metabolitov arakhidonovoi kisloty kletkami krovi u detei s glomerulonefritom, assotsiirovannym s HB-virusnoi infektsiei, na fone lecheniia reaferonom.

The efficacy of therapy with reaferon (recombinant alpha 2-interferon) was studied in children with glomerulonephritis (GN) associated with hepatitis B virus infection as well as its effect on the interferon status (IFN), production of interleukins (IL) 1 and 2 and synthesis of active arachidonic acid (AA) metabolites by the blood cells in the course of treatment. The IFN status, IL-1, IL-2 production, and synthesis of AA active metabolites (LTB 4- and 5-HETE) by the blood cells, as well as markers of HBV-infection (HBsAg, anti-HBs, anti-HBc total and anti-HBc of the IgM class) were examined over time in 60 GN patients treated with reaferon alone and administered immunosuppression therapy (IST), with antioxidants, or IST alone. The employment of reaferon for treatment of GN patients was shown to increase the efficacy of GN treatment, especially in combination with immunosuppressive drugs, to prevent reactivation of hepatitis B virus when prednisolone and/or cytostatic drugs were used, and to reduce hepatitis activity. It way be assumed that the above effects were mainly due to the action of reaferon and antioxidants on the improvement of the condition of immunocompetent cells, primarily monocyte-macrophage system and leukocytes. During reaferon therapy, normalization of alpha-IFN and IL-1 production by the blood cells and inhibition of production of AA active metabolites were observed.

[Study of serum levels of alpha 1-antitrypsin and alpha macroglobulins in children with glomerulonephritis]. / Issledovanie alpha 1-ingibitora proteinaz i alpha 2-makroglobulina v syvorotke krovi pri glomerulonefrite u detei.

To define the clinico-pathogenetic importance of alpha 1-inhibitor of proteinases and alpha 2-macroglobulin of the blood in children with glomerulonephritis, a study was made of the phenotype of alpha 1-inhibitor of proteinases and its concentration in the blood serum of 156 patients with different clinical forms of glomerulonephritis. Overall 1290 practically healthy children were examined as control. The patients suffering from glomerulonephritis did not demonstrate phenotypes responsible for acute deficiency of alpha 1-inhibitor of proteinases (PISS, PISZ). A relationship was established between the amount of alpha 1-inhibitor of proteinases in the blood serum in children with different clinical forms of glomerulonephritis: the patients with the nephrotic form manifested a significant decrease of the inhibitor concentration in the blood serum, whereas in the hematuric form, a significant rise of it was recorded. All the patients suffering from glomerulonephritis showed a significant increase of the content of alpha 2-macroglobulin, particularly in the nephrotic form, which is likely to be determined by the enhanced output of the given protein and its negligible loss with urine in connection with a high molecular weight.

[Presence of markers of hepatitis B in patients with nephrotic syndrome]. / Chastota markerov HB-virusnoi infektsii u bol'nykh s nefroticheskim sindromom.

The purpose of the present work was to study the rate of HB viral infection from the standpoint of its pathogenetic importance in children with the nephrotic syndrome (NS). As many as 71 children aged 2 to 15 years with the NS were examined. 23 children with hematuric glomerulonephritic (GN) served as control. HB viral infection markers (HBsAg, anti-HBs, total anti-HBc and IgM anti-HBc) were detected in the blood serum by means of IEA in all the patients. The examinations made it possible to reveal material differences in the distribution of various combinations of VHB markers in children with the NS and hematuric GN. The combination of HBsAg and IgM anti-HBc turned out most characteristic for the NS, pointing to active NB viral infection. In patients with mixed GN, that combination was detectable twice as often. The data obtained attest te a high rate of the association of HB viral infection with GN, particularly with that running its course with the NS. In this case, the rate mentioned was significantly higher than in the population. A definite relationship between the activity of HB viral infection and the gravity of the NS suggests that VHB is implicated in the pathogenesis of GN. This suggestion may be indirectly supported by a far higher rate of HBsAg and IgM anti-HBc demonstration in patients suffering from membranoproliferative GN.

[A method of separate determination of enzymuria associated with impairment of glomerular filtration in kidney tissue]. / Sposob razdel'nogo opredeleniia fermenturii, sviazannoi s povrezhdeniem glomeruliarnogo fil'tra i pochechnoi tkani.

Possibility of separate estimation of urinary enzymes after impairment of glomerular system and kidney tissue was considered theoretically. Activities of lactate dehydrogenase, alkaline phosphatase, aminopeptidase and gamma-glutamyl transferase were studied in blood serum and urine of II patients with nephrotic syndrome (4 patients with nephrotic form of glomerulonephritis and 7 patients with mixed form of glomerulonephritis). Urinary enzymes derived from blood serum constituted 20-30% of total enzymatic activity in urine of the patients with mixed form of glomerulonephritis and it was related only to the blood serum enzymes with relatively low molecular mass and high activity (alkaline phosphatase and LDH). The results obtained are consistent with the published data showing that kidney tissue is mainly responsible for appearance of the enzymes in urine.

[Clinical significance of enzymuria in glomerulonephritis in children]. / Klinicheskoe znachenie fermenturii pri glomerulonefrite u detei.

The authors presented the results of a study of enzymuria (cholinesterase, gamma-glutamine transferase, alkaline phosphatase, beta-galactosidase and lactate dehydrogenase with separate determination of N- and M-subunits) in 20 patients with a mixed form of glomerulonephritis (GN), 36 with the nephrotic form of GN and 13 patients with the hematuric form of GN. The clinical importance of the determination of enzymatic activity in the urine in GN of children lies in the recognition of the degree of damage of the glomerular filter as well as the nephrothelium. Basing on enzymuria pathophysiological syndromes found in various combinations in the above forms of GN were identified. Three degrees of damage of the permeability of the glomerular filter were defined for high molecular proteins. Differences in individual values of the activity of some enzymes gave rise to differential-diagnostic coefficients as well as differential-diagnostic tables which could be used for differential diagnosis between the GN mixed and nephrotic forms.