Inledning: Jodkontrastmedel är ett läkemedel som administreras av röntgensjuksköterskan för att förbättra kontrasten mellan inre organ och vävnader samt skilja mellan normala och patologiska områden. Jodkontrastmedel gavs uppskattningsvis i 80 miljoner doser över hela världen år 2003. Av kontrastmedel kan allvarlig biverkning eller till och med ett livshotandetillstånd uppkomma som kontrastmedelsinducerad nefropati (KMN). N-Acetylcystein (NAC) har flera egenskaper, bland annat antioxidfunktioner och förbättring av njurarnas perfusion som kan vara bidragande egenskaper till att förebygga KMN. Syfte: Denna litteraturöversikt var att sammanställa om N-Acetylcystein (NAC) är ett effektivt hydreringsalternativ för att förebygga kontrastmedelsinducerad nefropati (KMN) Metod: Studien utfördes som en allmänlitteraturöversikt. Tio vetenskapliga artiklar kvalitetsgranskades, analyserades och resultatet presenterades i kategorier. Resultat: Analysen av tio artiklar resulterade i sex kategorier, om NAC har en bra hydrerande effekt mot KMN, högriskpatienternas utveckling av KMN och NAC:s effekt, kontrastmedelsdos, mätvärden kontrollerade med serumkreatinin och cystatin C, biverkningar från oral och intravenös administration av NAC samt studiernas definition på KMN. Slutsats: NAC tillsammans med hydrering har visat sig i vissa studier vara effektivt mot KMN men det är ändå oklart om det är NAC som ger den positiva effekten. NAC tillsammans med hydrering verkar inte ge några negativa effekter för patienten då NAC har få biverkningar och är ett billigt läkemedel, men röntgensjuksköterskan bör ge kontrastmedelsdos enligt uträknad GFR. / Introduction: Iodine contrast media is a drug that is administered by the radiographer to enhance the contrast between the internal organs and tissues and distinguish between normal and pathological areas. Iodine contrast media is given estimated to 80 million dosesworldwide year 2003. By contrast media, a serious side effect or even a life-threatening condition can arise like contrast induced nephropathy (CIN). N-Acetylcysteine (NAC) has acapacity of antioxidant functions and improvement of renal perfusion, which may be properties to help and prevent CIN. Purpose: This literature review was to compile if N-Acetylcysteine (NAC) is an effective hydrations alternative to prevent contrast induced nephropathy (CIN) Method: The study was conducted as a general literature review. Tenquality scientific articles were reviewed, analyzed and the results were presented in categories. Results: The analysis of the ten articles resulted in six categories, the NAC has a good dehydrating effect against KMN, high-risk patients, the development of KMN and NAC:s effect, contrast media, measurements controlled by serum creatinine and cystatin C, side effects from oral and intravenous administration of NAC and studies definition of KMN Conclusions: NAC with hydration has been shown in some studies to be effective against KMN but it is still unclear whether it is NAC that gives the positive effect. We believe that NAC along with hydration do not hurt to give to the patient when the NAC has few side effects and is an inexpensive drug, but radiographer should give contrast media according to calculated GFR.

Adverse events that cause stress during the early stages of life may alter the normal development of the brain and neuroendocrine system and increase the vulnerability of the individual to various disorders. Chronic stress and subsequent releasing of stress mediators can lead to oxidative stress and cell damage. The first aim of this work was to determine selected oxidative stress markers in the cerebral cortex, hippocampus, and cerebellum after the exposure of rats to early life stress. To model the stressful situation, we used maternal separation of the offspring for three hours a day during the first three weeks of life. We choose reduced glutathione, protein carbonyls, lipid peroxides and hydroperoxides as typical markers. These markers were determined in the brains of rats aged 22 days. Any significant changes were found in the levels of the studied markers after maternal separation. Damage to brain cells may also be reflected in behavior. Studies of numerous neuropsychiatric and neurodegenerative diseases have indicated that oxidative stress is a promising candidate for inducing changes at the cellular level. The second aim of this work was to monitor the behavior of rats by the light/dark box test after maternal separation along with administration of N-acetylcysteine (NAC), a drug with...

Produtos de glicação avançada (AGE) contribuem para o estresse oxidativo e inflamatório, os quais constituem as bases celulares para as complicações a longo prazo do diabete melito (DM). A albumina é a principal proteína sérica modificada por AGE e afeta adversamente o metabolismo de lípides e a resposta infamatória em macrófagos, a função das ilhotas pancreáticas e a sensibilidade insulínica no músculo. Neste estudo, avaliamos o efeito da administração crônica de albumina AGE, associada ou não ao tratamento com N-acetilcisteína (NAC), sobre a sensibilidade periférica à insulina, infiltrado total e perfil de macrófagos, transcriptoma do tecido adiposo periepididimal e padrão de diferenciação de macrófagos peritoneais em ratos saudáveis. Albumina AGE foi produzida pela incubação de albumina de rato com glicolaldeído 10 mM, durante 4 dias a 37 °C, em agitação, no escuro. Albumina controle (C) foi preparada na presença de PBS apenas. Ratos Wistar com 4 semanas de idade foram divididos aleatoriamente em quatro grupos experimentais (n = 7-8), os quais receberam injeção intraperitoneal diária de albumina C ou albumina AGE (20 mg/Kg/dia) concomitantemente ou não a administração da NAC (600mg/L de água) (grupos albumina C + NAC e albumina AGE + NAC), durante 90 dias consecutivos. Parâmetros bioquímicos foram determinados por técnicas enzimáticas, peroxidação lipídica, pela medida de substâncias reativas ao ácido tiobarbitúrico (TBARS) na urina, expressão gênica, por RT-qPCR, e conteúdo proteico, por imuno-histoquímica. AGE total foi determinado por ELISA, carboximetil-lisina (CML) e pirralina (PYR), por cromatografia líquida/espectrometria de massa. O tecido adiposo periepididimal foi analisado por estereologia. A concentração de AGE total, CML e PYR foi, respectivamente, 9,2, 7000 e 235 vezes maior na albumina AGE em comparação à C. Consumo de ração, massa corporal, pressão arterial sistólica e concentração plasmática de colesterol total, triglicérides, ácidos graxos livres, glicose, insulina, ureia, creatinina, alanina aminotransferase, aspartato aminotransferase e excreção urinária de proteínas (24 h) foram semelhantes entre os grupos. A NAC reduziu em 1,4 e 1,6 vezes a concentração urinária de TBARS nos animais tratados com albumina AGE + NAC, em comparação aos grupos AGE e C+NAC, respectivamente. A albumina AGE reduziu em, aproximadamente, 1,4 vezes a sensibilidade à insulina em comparação ao C, o que foi prevenido pela NAC. O peso relativo do tecido adiposo periepididimal, a fração de área e o volume dos adipócitos foram semelhantes entre os grupos experimentais. Maior infiltrado macrofágico, (células F4/80 positivas), foi observado nos animais tratados com albumina AGE (1,3 x), o que também foi prevenido pela NAC. CD11b e CD206 permaneceram inalterados. O tratamento com albumina AGE também não alterou a expressão do mRNA de Ager (RAGE), Ddost (AGE-R1), Cd36, Nfkb1, Il6, Il10, Tnf, Nos2, Il12. No entanto, Itgam (CD11b - M1) e Mrc foram reduzidos no grupo AGE + NAC em comparação a C + NAC (2 e 1,9 x) e AGE (1,8 e 1,5 x, respectivamente). Aumento do mRNA de Slc2a4 (GLUT-4) e Ppara foi observado nos animais tratados com albumina AGE + NAC em comparação a C + NAC (Slc2a4: 1,6; Ppara 2,2 x) e AGE (2,3; 3,3 x). A albumina AGE contribuiu para maior expressão do Col12a1 (3,1 x) em relação ao C. Análise de macrófagos isolados da cavidade peritoneal apontaram elevação no mRNA de Il6 (2,6 x) e Ddost (1,4 x) no grupo AGE em relação ao C. Ddost também foi aumentado (1,2 x) no grupo AGE + NAC quando comparado ao C+NAC. Além disso, a NAC favoreceu o aumento do Arg1 (arginase 1) nos grupos albumina C + NAC (2,5 x) e AGE + NAC (2,6 x) quando comparados aos seus respectivos controles. Em conclusão, a albumina AGE favorece o infiltrado de macrófagos no tecido adiposo o que evidencia a sensibilização deste território à ação dos AGE e pode, a longo prazo, contribuir para piora na resistência à insulina, observada neste modelo animal. A NAC antagoniza os efeitos da albumina AGE e exerce, por si, efeitos benéficos sobre o perfil de diferenciação de macrófagos no tecido adiposo e peritônio, resposta inflamatória, peroxidação lipídica e resistência insulínica. A NAC pode ser uma ferramenta útil na prevenção das ações dos AGE sobre o desenvolvimento de resistência insulínica e complicações do DM / [Thesis]. São Paulo: \"Faculdade de Medicina, Universidade de São Paulo, 2016\". Advanced glycation end-products (AGE) contribute to oxidative and inflammatory stress, which constitute the cellular basis for long-term complications of diabetes mellitus (DM). Albumin is the major serum protein modified by AGE and adversely affects macrophage lipid metabolism and inflammatory response, pancreatic islet function and muscle insulin sensitivity. We investigated the effect of chronic administration of AGE-albumin, associated or not with N-acetylcysteine (NAC) treatment, in peripheral insulin sensitivity, macrophage infiltration and polarization and transcriptome of periepididimal adipose tissue and peritoneal macrophage differentiation in healthy rats. AGE-albumin was prepared by incubating rat albumin with 10 mM glycolaldehyde for 4 days, 37 °C, under shaker, in the dark. Control albumin (C) was incubated with PBS alone. Four-weeks old male Wistar rats (n = 7-8/group) were randomized into four groups receiving daily intraperitoneal injections of C or AGE albumin (20 mg/kg/day) alone or together with NAC (600mg/L drinking water) (C + NAC albumin and AGE + NAC albumin), for 90 consecutive days. Biochemical parameters were determined by enzymatic techniques, lipid peroxidation by the measurement of urinary thiobarbituric acid reactive substances (TBARS), gene expression by RT-qPCR and protein content by immunohistochemistry. Total AGE was determined by ELISA and carboxymethyllysine (CML) and pyrraline (PYR) by liquid chromatography/ mass spectrometry. Periepididimal adipose tissue was analyzed by stereology. Total AGE concentration, CML and PYR were, respectively, 9.2, 7000 and 235 times higher in AGE albumin as compared to C. Food consumption, body weight, systolic blood pressure and plasma total cholesterol, triglycerides, free fatty acids, glucose, insulin, urea, creatinine, alanine aminotransferase, aspartate aminotransferase and urinary protein excretion (24 h) were similar among groups. NAC reduced urinary TBARS in AGE + NAC group as compared to AGE (1.4 x) and C + NAC (1.6 x), respectively. AGE albumin reduced 1.4 times the insulin sensitivity as compared to C albumin; this was prevented by NAC. Adipose tissue relative weight, adipocyte area fraction and volume were similar among groups. A higher (1.3 x) macrophage infiltrate (F4/80 positive cells) was observed in AGE albumin treated animals in comparison to those treated with C albumin and this was prevented by NAC. CD11b and CD206 were unchanged as well as mRNA de Ager (RAGE), Ddost (AGE-R1), Cd36, Nfkb1, Il6, Il10, Tnf, Nos2 and Il12. Itgam (CD11b - M1) and Mrc (CD206 - M2) were reduced in AGE + NAC group in comparison to C + NAC (2 and 1.9 x, respectively) and AGE (1.8 and 1.5 x, respectively). Increased Slc2a4 (GLUT-4) and Ppara mRNA were observed in AGE + NAC group in comparison to C + NAC (Slc2a4: 1.6 x; Ppara: 2.2 x) and to AGE (Slc2a4: 2.3 x; Ppara: 3.3 x). AGE albumin increased the expression of Col12a1 in 3.1 times as compared to C albumin. In peritoneal macrophages there was an increase in Il6 (2.6 x) and Ddost (1.4 x) in AGE group as compared to C. Ddost was also 1.2 times increased in AGE + NAC as compared to C+NAC. NAC increased Arg1 (arginase 1) in C + NAC (2.5 x) and AGE + NAC (2.6 x) as compared to their respective controls. In conclusion, AGE albumin favors macrophage infiltration in adipose tissue promoting over time tissue sensitization to AGE that may contribute to worsening insulin resistance in this animal model. NAC antagonizes the effects of AGE albumin and by itself has beneficial effects in macrophage differentiation in adipose tissue and peritoneal cavity, inflammatory response, lipid peroxidation and insulin sensitivity. NAC may be a useful tool in the prevention of AGE actions on the development of insulin resistance and long-term complications of DM

Produtos de glicação avançada (AGE) contribuem para o estresse oxidativo e inflamatório, os quais constituem as bases celulares para as complicações a longo prazo do diabete melito (DM). A albumina é a principal proteína sérica modificada por AGE e afeta adversamente o metabolismo de lípides e a resposta infamatória em macrófagos, a função das ilhotas pancreáticas e a sensibilidade insulínica no músculo. Neste estudo, avaliamos o efeito da administração crônica de albumina AGE, associada ou não ao tratamento com N-acetilcisteína (NAC), sobre a sensibilidade periférica à insulina, infiltrado total e perfil de macrófagos, transcriptoma do tecido adiposo periepididimal e padrão de diferenciação de macrófagos peritoneais em ratos saudáveis. Albumina AGE foi produzida pela incubação de albumina de rato com glicolaldeído 10 mM, durante 4 dias a 37 °C, em agitação, no escuro. Albumina controle (C) foi preparada na presença de PBS apenas. Ratos Wistar com 4 semanas de idade foram divididos aleatoriamente em quatro grupos experimentais (n = 7-8), os quais receberam injeção intraperitoneal diária de albumina C ou albumina AGE (20 mg/Kg/dia) concomitantemente ou não a administração da NAC (600mg/L de água) (grupos albumina C + NAC e albumina AGE + NAC), durante 90 dias consecutivos. Parâmetros bioquímicos foram determinados por técnicas enzimáticas, peroxidação lipídica, pela medida de substâncias reativas ao ácido tiobarbitúrico (TBARS) na urina, expressão gênica, por RT-qPCR, e conteúdo proteico, por imuno-histoquímica. AGE total foi determinado por ELISA, carboximetil-lisina (CML) e pirralina (PYR), por cromatografia líquida/espectrometria de massa. O tecido adiposo periepididimal foi analisado por estereologia. A concentração de AGE total, CML e PYR foi, respectivamente, 9,2, 7000 e 235 vezes maior na albumina AGE em comparação à C. Consumo de ração, massa corporal, pressão arterial sistólica e concentração plasmática de colesterol total, triglicérides, ácidos graxos livres, glicose, insulina, ureia, creatinina, alanina aminotransferase, aspartato aminotransferase e excreção urinária de proteínas (24 h) foram semelhantes entre os grupos. A NAC reduziu em 1,4 e 1,6 vezes a concentração urinária de TBARS nos animais tratados com albumina AGE + NAC, em comparação aos grupos AGE e C+NAC, respectivamente. A albumina AGE reduziu em, aproximadamente, 1,4 vezes a sensibilidade à insulina em comparação ao C, o que foi prevenido pela NAC. O peso relativo do tecido adiposo periepididimal, a fração de área e o volume dos adipócitos foram semelhantes entre os grupos experimentais. Maior infiltrado macrofágico, (células F4/80 positivas), foi observado nos animais tratados com albumina AGE (1,3 x), o que também foi prevenido pela NAC. CD11b e CD206 permaneceram inalterados. O tratamento com albumina AGE também não alterou a expressão do mRNA de Ager (RAGE), Ddost (AGE-R1), Cd36, Nfkb1, Il6, Il10, Tnf, Nos2, Il12. No entanto, Itgam (CD11b - M1) e Mrc foram reduzidos no grupo AGE + NAC em comparação a C + NAC (2 e 1,9 x) e AGE (1,8 e 1,5 x, respectivamente). Aumento do mRNA de Slc2a4 (GLUT-4) e Ppara foi observado nos animais tratados com albumina AGE + NAC em comparação a C + NAC (Slc2a4: 1,6; Ppara 2,2 x) e AGE (2,3; 3,3 x). A albumina AGE contribuiu para maior expressão do Col12a1 (3,1 x) em relação ao C. Análise de macrófagos isolados da cavidade peritoneal apontaram elevação no mRNA de Il6 (2,6 x) e Ddost (1,4 x) no grupo AGE em relação ao C. Ddost também foi aumentado (1,2 x) no grupo AGE + NAC quando comparado ao C+NAC. Além disso, a NAC favoreceu o aumento do Arg1 (arginase 1) nos grupos albumina C + NAC (2,5 x) e AGE + NAC (2,6 x) quando comparados aos seus respectivos controles. Em conclusão, a albumina AGE favorece o infiltrado de macrófagos no tecido adiposo o que evidencia a sensibilização deste território à ação dos AGE e pode, a longo prazo, contribuir para piora na resistência à insulina, observada neste modelo animal. A NAC antagoniza os efeitos da albumina AGE e exerce, por si, efeitos benéficos sobre o perfil de diferenciação de macrófagos no tecido adiposo e peritônio, resposta inflamatória, peroxidação lipídica e resistência insulínica. A NAC pode ser uma ferramenta útil na prevenção das ações dos AGE sobre o desenvolvimento de resistência insulínica e complicações do DM / [Thesis]. São Paulo: \"Faculdade de Medicina, Universidade de São Paulo, 2016\". Advanced glycation end-products (AGE) contribute to oxidative and inflammatory stress, which constitute the cellular basis for long-term complications of diabetes mellitus (DM). Albumin is the major serum protein modified by AGE and adversely affects macrophage lipid metabolism and inflammatory response, pancreatic islet function and muscle insulin sensitivity. We investigated the effect of chronic administration of AGE-albumin, associated or not with N-acetylcysteine (NAC) treatment, in peripheral insulin sensitivity, macrophage infiltration and polarization and transcriptome of periepididimal adipose tissue and peritoneal macrophage differentiation in healthy rats. AGE-albumin was prepared by incubating rat albumin with 10 mM glycolaldehyde for 4 days, 37 °C, under shaker, in the dark. Control albumin (C) was incubated with PBS alone. Four-weeks old male Wistar rats (n = 7-8/group) were randomized into four groups receiving daily intraperitoneal injections of C or AGE albumin (20 mg/kg/day) alone or together with NAC (600mg/L drinking water) (C + NAC albumin and AGE + NAC albumin), for 90 consecutive days. Biochemical parameters were determined by enzymatic techniques, lipid peroxidation by the measurement of urinary thiobarbituric acid reactive substances (TBARS), gene expression by RT-qPCR and protein content by immunohistochemistry. Total AGE was determined by ELISA and carboxymethyllysine (CML) and pyrraline (PYR) by liquid chromatography/ mass spectrometry. Periepididimal adipose tissue was analyzed by stereology. Total AGE concentration, CML and PYR were, respectively, 9.2, 7000 and 235 times higher in AGE albumin as compared to C. Food consumption, body weight, systolic blood pressure and plasma total cholesterol, triglycerides, free fatty acids, glucose, insulin, urea, creatinine, alanine aminotransferase, aspartate aminotransferase and urinary protein excretion (24 h) were similar among groups. NAC reduced urinary TBARS in AGE + NAC group as compared to AGE (1.4 x) and C + NAC (1.6 x), respectively. AGE albumin reduced 1.4 times the insulin sensitivity as compared to C albumin; this was prevented by NAC. Adipose tissue relative weight, adipocyte area fraction and volume were similar among groups. A higher (1.3 x) macrophage infiltrate (F4/80 positive cells) was observed in AGE albumin treated animals in comparison to those treated with C albumin and this was prevented by NAC. CD11b and CD206 were unchanged as well as mRNA de Ager (RAGE), Ddost (AGE-R1), Cd36, Nfkb1, Il6, Il10, Tnf, Nos2 and Il12. Itgam (CD11b - M1) and Mrc (CD206 - M2) were reduced in AGE + NAC group in comparison to C + NAC (2 and 1.9 x, respectively) and AGE (1.8 and 1.5 x, respectively). Increased Slc2a4 (GLUT-4) and Ppara mRNA were observed in AGE + NAC group in comparison to C + NAC (Slc2a4: 1.6 x; Ppara: 2.2 x) and to AGE (Slc2a4: 2.3 x; Ppara: 3.3 x). AGE albumin increased the expression of Col12a1 in 3.1 times as compared to C albumin. In peritoneal macrophages there was an increase in Il6 (2.6 x) and Ddost (1.4 x) in AGE group as compared to C. Ddost was also 1.2 times increased in AGE + NAC as compared to C+NAC. NAC increased Arg1 (arginase 1) in C + NAC (2.5 x) and AGE + NAC (2.6 x) as compared to their respective controls. In conclusion, AGE albumin favors macrophage infiltration in adipose tissue promoting over time tissue sensitization to AGE that may contribute to worsening insulin resistance in this animal model. NAC antagonizes the effects of AGE albumin and by itself has beneficial effects in macrophage differentiation in adipose tissue and peritoneal cavity, inflammatory response, lipid peroxidation and insulin sensitivity. NAC may be a useful tool in the prevention of AGE actions on the development of insulin resistance and long-term complications of DM

Introduction: Triple A syndrome (AAAS) is a rare autosomal recessive disorder characterized by alacrima, achalasia, ACTH-resistant adrenal insufficiency, autonomic dysfunction, and progressive neurodegeneration. Increased oxidative stress, demonstrated in patients’ fibroblasts in vitro, may be a central disease mechanism. N-acetylcysteine protects renal function in patients with kidney injuries associated with increased oxidative stress and improves viability of AAAS-knockdown adrenal cells in vitro. Patient and Results: A boy diagnosed with AAAS presented with short stature and increased oxidative stress in vivo assessed by increased thiobarbituric acid reactive substances (TBARS), which are markers of lipid peroxidation, and by the susceptibility of LDL to oxidation and the capacity of HDL to prevent it. A homozygous missense germline mutation (c.523G>T, p.Val175Phe) in AAAS was identified. N-acetylcysteine (600 mg orally, twice daily) decreased oxidative stress but did not change the patient’s growth pattern. Conclusions: An increase in oxidative stress is reported for the first time in vivo in an AAAS patient. N-acetylcysteine was capable of decreasing TBARS levels, reducing the susceptibility of LDL to oxidation and improving the antioxidant role of HDL. The longterm effect of antioxidant treatment should be evaluated to determine the real benefit for the prevention of the degenerative process in AAAS.

No description available.

Störungen im Bereich der Mikrozirkulation gelten als ursächlich für die Entstehung des Multiorganversagens bei Sepsis, wobei der Darm eine zentrale Rolle einnimmt. Aktivierte Leukozyten setzen u.a. Sauerstoffradikale frei, die entscheidend zur Zerstörung der endothelialen Integrität beitragen. Die Antagonisierung schädigender Mediatoren stellt ein Prinzip der adjunktiven Sepsis-Therapie dar, wobei die antioxidativ wirkenden Substanzen N-Acetylcystein (NAC) und Tirilazad Mesylat (TM) in mehreren Studien positive Effekte gezeigt haben. In einer tierexperimentellen Untersuchung an Ratten wurde der Effekt der kombinierten Gabe von NAC und TM auf die mesenteriale Mikrozirkulation, auf die Freisetzung von TNF-alpha, IL-1beta, IL-6, IL-10 und auf die Leukozytenzahl unter einer kontinuierlichen Lipopolysaccharidbelastung (LPS) von 10 mg/kg KG untersucht. Die Beurteilung der mesenterialen Mikrozirkulation erfolgte mittels Intravitalmikroskopie. Hierbei wurde das Ausmaß der Leukozytenadhärenz am Endothel der mesenterialen Venolen als Maß für die Leukozytenaktivierung und die Plasmaextravasation als Parameter für die Endotheldysfunktion bestimmt. Dabei konnte während zwei Stunden Endotoxinämie die Zunahme der Plasmaextravasation an mesenterialen Venolen durch die kombinierte Gabe von NAC und TM nicht signifikant beeinflusst werden (p>0,05). Eine tendenziell erhöhte Plasmaextravasation unterstützt die Hypothese, dass leukozytenunabhängige Mechanismen für die Plasmaextravasation existieren. Während zwei Stunden Endotoxinämie kam es zu einer signifikanten Reduktion der Anzahl der fest adhärenten Leukozyten in der NAC/TM-Gruppe im Vergleich zur LPS-Gruppe (p=0,001). Durch die kombinierte Gabe von NAC und TM konnte die endotoxininduzierte Freisetzung von TNF-alpha, IL-1beta, IL-6, IL-10 und die endotoxinbedingte Leukopenie nicht signifikant beeinflusst werden. / Disturbances of the microcirculation are causal for the pathophysiology of multiorgan failure related to sepsis in which the gut plays a central part. Activated leukocytes release i.e. oxygen radicals which decisively contribute to the destruction of the endothelial integration. To antagonize the damaging mediators is a principle of the adjunctive sepsis therapy in which the antioxidant agents N-acetylcysteine (NAC) and tirilazad mesylate (TM) showed positive effects in several studies. The effect of the combined administering of NAC and TM under continuous lipopolysaccharide (LPS) exposure of 10 mg/kg BW on the mesenteric microcirculation, on the release of TNF-alpha, IL-1beta, IL-6, IL-10 and on the number of leukocytes was examined in an animal study on rats. The appraisal of the microcirculation was done by intravital microscopy. The degree of leukocyte adherence on the endothelium of mesenteric venules was determined for the degree of leukocyte activation, and the plasma extravasation was the parameter for the endothelial dysfunction. The increase of plasma extravasation on mesenteric venules during 2 hours of endotoxemia could not be affected significantly by the combined administering of NAC and TM. The tendency of increased plasma extravasation supports the hypothesis of the existence of a leukocyte independent mechanism of plasma extravasation. During 2 hours of endotoxemia the NAC/TM group showed a significant decrease in the number of firmly adherent leukocytes in comparison to the LPS group. There was no significant effect on the endotoxin induced release of TNF-alpha, IL-1beta, IL-6, IL-10 and the endotoxin induced leukopenia by the combined administration of NAC and TM.

Therapeutic hypothermia (TH) is the only clinically used intervention that suppresses nearly all manifestations of ischemia-reperfusion injury after cardiac arrest. Experimental models has proven that exogenous antioxidants have positive impact on ischemia-reperfusion injury and it is able to prevent it as well. Results in this thesis are based on application of high dosages of N-acetylcystein (NAC) on ischemia-reperfusion injury after experimental cardiac arrest in a porcine model. It was used as a form of monoteraphy or in combination with TH. During the experiment animals were randomized into 5 groups: administration of NAC and TH (group A), administration of NAC during cardiac arrest (group B), induction of TH (group C), without any intervention (group D) and administration of NAC after return of spontaneous circulation (group E). We were not able to confirm additive effect of NAC in combination with TH. Administration of NAC during cardiac arrest led to statistically important reduction of oxidative stress but in the same time anafylactic reaction led to higher mortality in group B and changes in hemodynamical parameters in group E. Key words: Therapeutic hypothermia, cardiac arrest, N-acetylcysteine, ischemia-reperfusion injury, cardiopulmonary resuscitation, oxidative stress, oxygen radicals