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The aim of the study was to determine the impact of gene polymorphism for cytokines tumor necrosis factor alpha (TNF-α ), transforming growth factor beta 1 (TGF-β 1), interleukin 10 (IL-10), interleukin 6 (IL-6) and interferon gamma (IFN-γ ) on acute rejection occurrence in kidney transplantation. Study included 50 adult patients (21 males, 29 females) with the first cadaveric kidney transplant. Gene polymorphism for TNF-α , TGF-β 1, IL-10, IL-6 and IFN-γ was determined using Cytokine Genotyping Tray (One Lambda Inc., Canoga Park, CA, USA) from DNA isolated from peripheral blood leukocytes by polymerase chain reaction sequence specific primers (PCR-SSP) method. According to the obtained genotype patients were grouped into the certain level of cytokine production as following: for TNF-α and IL-6- low and high producers, and for TGF-β 1, IL-10 and IFN-γ - high, intermediate and low producers. Data on history of acute rejection were taken from medical records. The diagnosis was made based on clinical signs or was biopsy proven. There were 19 patients with history of acute rejection. Patients with history of acute rejection did not differ significantly from those without rejection episodes in TNF-α , TGF-β 1, IL10 and IL-6 genotypes. History of acute rejection differed significantly with respect to IFN-γ genotype (Chi-square=10.899, p=0.004). Patients with low producer AA genotype for IFN-γ (n=12) did not have acute rejection episodes. In conclusion, genotype for cytokines TNF-α , TGF-β 1, IL-10 and IL-6 was not associated with kidney allograft acute rejection occurrence. Low IFN-γ producer genotype seems to be protective against acute rejection of kidney transplant

Biomedical application of nanotechnology, such as early, in vivo disease detection and malignant cell destruction, were documentated using a small sized supermagnetic particles coated with specific antibodies. Antibody coated nanoparticles can be used as a contrast markers in magnetic resonance imaging of targeted cells and at the same time in temeprature induced specific destruction of these cells in situ, using external aletrnative magnetic field. Our experimetal results corroborate this hypothesis. Combined diagnosis with treatment, many considerable applications of nanotechnology in biomedicine could be performe, depending on availability of appropiate antibodies. This paper describes strategy for future developments and multidisciplinary approach involved in the preparation and handling of nanoparticles and experimental design.

Biomedical applications of nanotechology, such as early, in vivo disease detection and malignant cell destruction, were documented, using a small-sized superparamagnetic particles coated with specific antibodies. Antibody coated nanoparticles can be used as contrast markers in magnetic resonance imaging of targeted cells and at the same time in temperature induced specific destruction of these cells in situ, using external alternative magnetic field . Our experimental results corroborate this hypothesis. Combined diagnoses with treatments, many considerable applications of nanotechnology in biomedicine could be performed, depending on availability of appropriate antibodies. This paper describes strategy for future developments and multidisciplinary approach involved in the preparation and handling of nanoparticles and experimental design.

Bimedical applications of nanotechnology, such as early in vivo metastatic disease detection and specific cell destruction, were documneted, using small sized supermagnetic coated particles with specific antibodies. Antibody coated nanoparticles can be used as contrast markers in magnetic resonance imaging (MRI) of targeted cells and at the same time in temeprature induced specific, in situ destruction of these cells, using external alternative magnetic field application. Oure experimental results corroborate this hypothesis. Combined diagnosis with treatments many considerable applications of nanotechnology in biomedicine could be performed depending on availability of appropiate antibodies.

The antitumor effect of PS-K, a Coriolus versicolor preparation, was analyzed on the growth of tumor and the immune reaction in mice. It was shown that PS-K applied in a single dose, as well as repeatedly, systemically (per os or intraperitoneal) has no significant effect on the growth of tumor induced by methylcholantrene (Mch-13). On the other hand, PS-K has a strong antitumor effect on the Ehrilich ascites carcinoma (EAC), so that it can cause regression of already established tumor in about 50% of animals. Animals in which the tumor had regressed were resistant to tumor reinoculation. The inhibitory effect of PS-K on EAC is most probably based on the stimulated production of cytotoxic anti-EAC antibodies. PS-K has a markedly synergistic antitumor effect with cyclophosphamide (CY). Simultaneous application of PS-K and CY causes complete regression of already established methylcholantrene-induced tumor in about 40% of treated animals. In addition, PS-K decreases mortality and/ or prolongs the survival time of animals treated with a lethal dose of CY. PS-K does not prevent CY -toxicity on hematopoietic stem cells, so that the mechanism of its protective effect is not jet clear. In normal animals, intraperitoneal and peroral application of PS-K induces the increase of the mass and cellularity of the spleen, as well as the total number of leukocytes in the blood (mainly mononuclear cells). PS-K increased the mass of the mesenterial lymph node whi1e it decreased the mass of the thymus (especially when administrated i.p.). Peroral application decreased the mass of axillary lymph nodes, while i. p. application slightly increased it.

It is known that Kupffer and other non-parenchymal liver cells are activated in hepatic injury, even if this is induced acutely by administration of high doses of hepatotoxic drugs. These cells secrete prostaglandins, proinflammatory cytokines and other products, which may contribute to pathogenic or repair processes. In these experiments we investigated the role of prostaglandin E2 (PGE2), prostaglandin I2 (PGI2) and thromboxane (TXA2) in acute liver toxicity induced in mice by Paracetamol (acetaminophen, AAP). Mice were given a lethal dose of AAP by gastric lavage and production of PGs was determined in supernatants of short term culture of livers slices, taken from mice at various times (2-24 hours) after AAP administration. Several agents which are known to have hepatoprotective effect and/or modulate PG synthesis (IL-1 , ketoconazole and dipyiridamole) were given to mice 1-2 hours before AAP. The synthesis of all prostanoids was greatly increased in liver slices of mice given AAP in comparison to mice given saline. Pretreatment of mice with IL-1 before administration of AAP further increased the synthesis of PGE2 and PGI2 and reduced the synthesis of TXA2 in liver slices. These changes in level of PG synthesis were significant at most time observed time intervals after AAP administration. The effect of ketoconazole and dipyridamole on PG synthesis was measured only at 6 hour interval after AAP administration. Both agents had similar effect as IL-1 , i.e., they increased the synthesis of PGE2 or PGI2 and reduced the synthesis of TXA2. All agents had a significant protective effect in vivo when given before AAP, i.e., they reduced the mortality of mice and level of serum aminotransferases in survived mice (ALT and AST). 16-16-dimethyl-PGE 2 (a stable analogue of (PGE 2 ) had a strong protective effect if given to mice before or up to two hours after AAP. These data suggest that PGE2 and PGI2 might have a protective and TXA2 noxious effect in acute liver injury.

Blood concentration of lipid-bound sialic acid (LBSA), prostaglandin E (PGE) and histamine were determined in 37 patients with carcinoma of hypopharynx and larynx (supraglottic and glottic), in 12 non-cancer patients and in 10 healthy subjects. The concentration of LBSA was significantly increased in 94.4% cancer patients preoperatively and fell to somewhat lower levels within 1 month after tumour resection. In patients with complete tumour resection and no tumour recurrences within 2 years, it steadily decreased thereafter, reaching normal levels within 6-24 months after surgery, whereas in patients with tumour recurrences or incomplete tumour resection it rose again within 6 months after tumour resection. Similarly, the concentration of PGE was significantly increased in about two thirds of cancer patients (67.6%) preoperatively, dropped significantly within 1 month after tumour resection and rose again in patients with tumour recurrences. Preoperative histamine concentration was decreased in 24.3% of cancer patients and postoperatively it rose both in patients with or without tumour recurrences.

The protective effect of interleukin lα (IL-lα ) in mice with acetaminophen (AAP)-induced hepatitis was investigated. IL-lα had a significant protective effect if given 2 or more hours (up to 24 hours) before AAP ; it significantly reduced mortality of mice and decreased serum transaminase level. The maximal effect was obtained with the dose of 1000 U (166 ng/kg)IL-lalpha. Pretreatment with IL-1 significantly increased the synthesis of prostaglandin E, (PGE, )in samples of liver tissue from AAP-treated mice, but had no effect on the synthesis of leukotriene C, (LTC4). Pretreatment with indomethacin (IMC) did not abrogate significantly the protective effect of IL-l. Thus, the hepatoprotective effect of IL-lα can not be entirely explained by the stimulation of prostaglandin (PG) synthesis.

Acetaminophen (AAP) administered to mice via gastric tube in a dose of 300-350 mg/kg induced heavy liver injury and killed 55%- 80% mice within 48 hours. Dimethyl-16-16prostaglandin E2 (PGE2), given intraperitoneally (0.025-0.2 mg/kg) 15 to 30 minutes before AAP, ameliorated the liver injury and reduced the mortality in mice to 20%-30%. PGE2 also significantly reduced the increase in plasma transamina.se (ALT, AST) levels induced by AAP. In the same doses, PGE1 had a slight but not significantly protective effect. When given 2 hours after AAP administration, PGE2 delayed the death of mice but had no significant effect on total mortality. Pretreatment of mice with indomethacin (4 mg/kg i.p.) had no effect on AAP toxicity, while pretreatment of mice with specific anti-PGE2 antibodies increased this toxicity. Thus, PGE2 was concluded to have a protective role in AAP-induced hepatotoxicity.