The role of iNOS inhibition in the mechanism of the cardioprotective effect of new GABA and glutamic acid derivatives in the model of acute alcoholic myocardial injury in rats.

The cardioprotective effects of new derivatives of glutamic acid (glufimet) and GABA (mefargin) were studied in rats exposed to acute alcohol intoxication (AAI) under conditions of selective blockade of inducible NO-synthase (iNOS). AAI induced a pronounced decrease in the contractile function of the myocardium during exercise tests (load by volume, test for adrenoreactivity, isometric exercise), caused mitochondrial dysfunction and increased processes of lipid peroxidation (LPO) in heart cells. A decrease in NO production during iNOS inhibition and AAI improved the respiratory function of mitochondria, a decreased the level of LPO products, and increased mitochondrial superoxide dismutase activity of heart cells. This led to an increase in myocardial contractility. The studied compounds, glufimet and mefargin, caused a statistically significant increase in the rates of myocardial contraction and relaxation, left ventricular pressure, and also reduced NO production. This was accompanied by a decrease in the intensity of LPO processes and an increase in the respiratory control ratio (RCR), reflecting the coupling between respiration and phosphorylation processes during activation of the respiratory chain complexes I and II. The decrease in NO concentration during selective blockade of iNOS and administration of the studied substances was less pronounced than without blockade of the enzyme. This suggests the putative effect of new derivatives of neuroactive amino acids on the NO system.

[Transplantations of allogenic and autologous hemopoietic stem cells in acute leukemia (results of 20-year experience)].

AIM: To analyse results of transplantation of allogenic and autologous hemopoietic stem cells (allo-THSC and auto-THSC) with myeloablation preconditioning in patients with acute leukemia (AL) performed in 1987-2006. MATERIAL AND METHODS: A total of 71 allogenic and 45 autologous THSC were performed in 116 patients with different AL variants. Conditioning in all allo-THSC included busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg). This regimen was used in 29 recipients of auto-HSC. Cyclophosphamide in a dose 120 mg/kg and total radiation of the body in a dose 12 Gy were given to 16 recipients. Overall, relapse-free and event-free survival of patients after THSC were analysed as well as early (first 100 days) and overall lethality. Auto-THSC in 15 patients was for the first time followed by immunomodulating therapy aimed at prevention of AL relapses: in acute myeloid leukemia ATRA in combination with alpha-interferon, in acute lymphoblastic leukemia (ALL)--ronkoleukin, interleukin-2 preparation. RESULTS: Overall survival of AL patients after allo-THSC for the observation period increased from 31 to 58%, early lethality fell from 44 to 4%. Results of allo-THSC conducted in the first complete remission were much better than in patients with other AL stages at the time of THSC. After auto-THSC 5-year survival rose from 22 to 60% while early lethality reduced from 33 to 4%. Administration of immunomodulating therapy after auto-THSC increases 5-year survival from 35 to 80%. CONCLUSION: Outcomes of THSC in AL has improved for the last 20 years. Outcomes of allo-THSC performed in the first complete remission are much higher. Immunomodulating therapy after auto-THSC promoted better results.

[The efficacy of high-dose chemotherapy and the transplantation of autologous hemopoietic cells in lymphogranulomatosis]. / Effektivnost' vysokodoznoi khimioterapii i transplantatsii autologichnykh gemopoéticheskikh kletok pri limfogranulematoze.

AIM: To determine clinical effectiveness of high-dose polychemotherapy (PCT) and transplantation of autologous hemopoietic cells (TAHC) in patients with lymphogranulomatosis (LGM). MATERIAL AND METHODS: 27 LGM patients aged 16-42 years who have undergone TAHC after high-dose PCT (BEAM--17 patients or CBV--10 patients). 4 patients given high-dose PCT were in the first-second complete remission (CR), 7 patients--in the first partial remission (PR). Prior to TAHC, 8 patients had one, two and more relapses of LGM, and 8 patients had no remission at all. Bone marrow, hemopoietic blood cells and both were transplanted to 17, 2 and 8 patients, respectively. Mobilization of hemopoietic blood cells and stimulation of hemopoiesis after TAHC were achieved using colony-stimulating factors. RESULTS: The treatment resulted in CR or PR (from 6 to 95 months) in 70.4% of patients. The remission duration varied depending on the disease phase at transplantation. Four patients who underwent TAHC in PR maintained it for 13-95 months (median 47.5 months). Lasting remissions (29-59 months) were achieved in 42.9 and 37.5% of patients who underwent TAHC in the first PR or in recurrent LGM. None of the patients was in remission longer than 2 years after TAHC if high-dose PCT was conducted in advanced tumor process due to resistant LGM or inadequate previous treatment. Infectious complications lethality early after the transplantation reached 7.4%(2 patients). CONCLUSION: High-dose PCT followed by TAHC is effective in LGM if the tumor is chemosensitive.

[The monitoring of protein-volemic indices during plasmapheresis in patients with paraproteinemic hemoblastoses]. / Monitoring belkovo-volemicheskikh pokazatelei pri plazmafereze u bol'nykh paraproteinemicheskimi gemoblastozami.

We studied quantitative characteristics of plasma protein before, during and after 133 plasmapheresis (PA) procedures in patients with multiple myeloma and Waldenstrom's macroglobulinemia. A value of removed plasma volume (RPV) was calculated as a part plasma volume (PV) before PA with consideration of quantity and consequence of replacement solution. In the case when we removed 30% of calculated PV we replaced it only with electrolyte solutions. In the case of 50% PV removing, the replacement was a combination of low molecular weight dextran and electrolyte solutions (1:2) or 5% albumin and electrolyte solutions. The results support correlation between a level of total protein and RPV, kind of replacement solutions. We recommend two regression equations for efficient and safety planning RPV and for prediction of protein level after PA. This simple and fast method can be used for prognosis of critic PA parameters, to decrease a risk of side effects and for optimal use of albumin replacement solutions.

[Neocytapheresis in donors]. / Neotsitaferez u donorov.

Various techniques and blood separators were employed to obtain therapeutic doses of immature erythrocytes (neocytes) from blood of 18 donors. Regimens of neocyte apheresis, preparative efficiency of blood separators, morphofunctional and biophysical characteristics of neocytes obtained were compared. Neocyte apheresis shows promise for hematological patients dependent on red cells transfusion.