No description available.

No description available.

No description available.

Die Hypothese, dass das AP Clozapin, ebenso wie dessen Metabolit NDMC die Produktion von TxA2 beeinfluss könnten, stellten wir nach ausführlicher Literaturrecherche auf. Letztere zeigte, dass bereits beim ersten AP CPZ eine reduzierende Wirkung auf die TxA2-Produktion nachgewiesen werden konnte. TxA2 und die Aktivierung seines Rezeptors modulieren Vasokonstriktion und Thrombozytenaggregation. Weiterhin nehmen sie Einfluss auf dopaminerge und serotonerge Signalwege. In der Pathophysiologie der Schizophrenie spielen eben diese eine bedeutende Rolle und stellen somit Zielstrukturen für APs dar. Um die Konzentration von TxB2, dem Metaboliten des instabilen Moleküls TxA2 in stimulierten und unstimulierten Blutproben 10 gesunder Probandinnen zu messen, verwendeten wir ein Vollblutverfahren. Um signifikante Ergebnisse zu erhalten, stimulierten wir die Proben mit TSST-1 oder dem monoklonalen Antikörper OKT3 (Muromonab-CD3), der gegen das Oberflächenantigen CD3 gerichtet ist, kombiniert mit dem monoklonalen Antikörper 5C3, der mit dem Protein CD40 interagiert und es stimuliert. Weiterhin versetzten wir das Blut mit den APs CPZ, Clozapin oder NDMC in einer von vier verschiedenen Konzentrationen. Außerdem wurden die Thromboxanspiegel im Blut ohne Zusatz von APs unter verschiedenen Stimulationskonditionen gemessen. Durch den Zusatz von Clozapin in den verschiedenen Konzentrationen kam es zu einer signifikanten (p<0.05) Verringerung der TxB2-Produktion in den mit TSST-1 und ebenso in den mit OKT3/5C3 versetzen Proben, was wir im Rahmen unserer Studie feststellen konnten. Weiterhin konnten wir zeigen, dass CPZ in sehr niedriger Konzentration die TxB2-Spiegel im unstimulierten und im mit TSST-1 stimulierten Blut reduziert. Daraus lässt sich schlussfolgern, dass Clozapin, NDMC und CPZ auch über eine Modulation der TxA2- und TxB2-Produktion das Neurotransmittersystem beeinflussen könnten. Auch typische Nebenwirkungen der AP, wie zum Beispiel die orthostatische Hypotension, könnten aus den Veränderungen der TxA2- und TxB2-Konzentrationen resultieren.

Introdução: O prognóstico da parada cardiorrespiratória (PCR) em ritmo não chocável (assistolia/atividade elétrica sem pulso) é ruim e não melhorou significativamente nas últimas décadas. Embora a epinefrina seja o vasopressor recomendado, há evidências de que ela eleva o consumo de oxigênio, reduz a pressão de perfusão subendocárdica, causa grave disfunção miocárdica e piora a microcirculação cerebral durante a ressuscitação cardiopulmonar. Vasopressina foi muito estudada nos últimos anos e não se mostrou superior à epinefrina. Naloxona e terlipressina têm sido cogitadas como potenciais vasopressores no tratamento da PCR, entretanto há poucos estudos publicados e os resultados são controversos e inconclusivos. Objetivos: Avaliar os efeitos hemodinâmicos e metabólicos da terlipressina ou naloxona na PCR induzida por hipóxia e compará-las com o tratamento-padrão (epinefrina ou vasopressina). Métodos: Estudo experimental, randomizado, cego e controlado. Ratos Wistar adultos, machos, foram anestesiados, submetidos a traqueostomia e ventilados mecanicamente. A PCR foi induzida por obstrução da traqueia e mantida por 3,5 minutos. Em seguida, os animais foram ressuscitados de forma padronizada e randomizados em um dos grupos: placebo (n = 7), vasopressina (n = 7), epinefrina (n = 7), naloxona (n = 7) ou terlipressina (n = 21). Variáveis hemodinâmicas foram monitorizadas durante todo o experimento (via cateter intra-arterial e intraventricular) e mensuradas na base, no 10o (T10), 20o (T20), 30o (T30), 45o (T45) e 60o (T60) minutos pós-PCR. Amostras de sangue arterial foram coletadas para gasometria, hemoglobina, bioquímica e lactato em quatro momentos [base, 11o (T11), 31o (T31), e 59o (T59) minutos pós-PCR]. Resultados: Os grupos foram homogêneos e não houve diferença significativa entre eles nas variáveis de base. O retorno da circulação espontânea ocorreu em 57% dos animais no grupo placebo (4 de 7) e 100% nos demais grupos (p = 0,002). A ! sobrevida em 1 hora foi de 57% no grupo placebo, 71,4% no grupo epinefrina, 90,5% no grupo terlipressina e de 100% nos demais grupos. Comparado com o grupo epinefrina, o grupo terlipressina teve maiores valores de PAM no T10 (164 vs 111 mmHg; p = 0,02), T20 (157 vs 97 mmHg; p < 0,0001), T30 (140 vs 67 mmHg; p < 0,0001), T45 (117 vs 67 mmHg; p = 0,002) e T60 (98 vs 62 mmHg; p = 0,026). O lactato arterial no grupo naloxona foi significativamente menor quando comparado ao grupo epinefrina, no T11 (5,15 vs 8,82 mmol/L), T31 (2,57 vs 5,24 mmol/L) e T59 (2,1 vs 4,1 mmol/L)[p = 0,002]. Ao longo da 1a hora pós-PCR, o grupo naloxona apresentou o melhor perfil do excesso de bases (-7,78 mmol/L) quando comparado ao grupo epinefrina (-12,78 mmol/L; p = 0,014) e ao grupo terlipressina (-11,31 mmol/L; p = 0,024). Conclusões: Neste modelo de PCR induzida por hipóxia em ratos, terlipressina e naloxona foram eficazes como vasopressores na RCP e apresentaram melhor perfil metabólico que a epinefrina. A terlipressina resultou em uma maior estabilidade hemodinâmica na 1a hora pós-PCR comparada com a epinefrina ou a vasopressina. Os efeitos metabólicos favoráveis da naloxona não são explicados pelos valores da PAM / Introduction: The prognosis of cardiac arrest (CA) with nonshockable rhythm (asystole/pulseless electrical activity) is poor and not improved significantly in recent decades. Epinephrine is the most commonly used vasopressor, although there is evidence that its use correlates with myocardial dysfunction and worsens the cerebral microcirculation. Vasopressin has been widely studied in recent years and was not superior to epinephrine. Naloxone and terlipressin have been considered as potential vasopressors in the treatment of CA, however, there are few published studies and the results are controversial and inconclusive. Objectives: To evaluate the hemodynamic and metabolic effects of terlipressin or naloxone in CA induced by hypoxia and compare with standard treatment with epinephrine or vasopressin. Methods: Experimental, randomized, blinded and controlled trial. Adult male Wistar rats were anesthetized, the proximal trachea was surgically exposed, and a 14-gauge cannula was inserted 10 mm into the trachea to the larynx. They were mechanically ventilated and monitored. The CA was induced by tracheal obstruction and maintained for 3.5 minutes. Subsequently, the animals were resuscitated using standard maneuvers and randomized to one of groups: placebo (n=7), vasopressin (n=7), epinephrine (n=7), naloxone (n=7) or terlipressin (n=21). Hemodynamic variables were monitored throughout the study (intra-arterial and intra-ventricular catheter) and measured at baseline, in the 10th (T10), 20th (T20), 30th (T30), 45th (T45) and 60th (T60) minute post-cardiac arrest. Arterial blood samples were collected for hemoglobin, biochemistry, blood gases and lactate at four moments: baseline, 11th (T11), 31st (T31) and 59th (T59) minute post-cardiac arrest. Results: The groups were homogenous and there were no significant differences among them regarding the baseline variables. The return of spontaneous circulation (ROSC) occurred in 57% of the animals (4 of 7) in the placebo group and in 100% in the ! other groups (P=0.002). One-hour survival was 57% in the placebo group, 71.4% in the epinephrine group, 90.5% in the terlipressin and 100% in the naloxone group. Compared with the epinephrine group, the terlipressin groups had a significantly higher MAP at the T10 (164 x 111 mmHg; P=0.02), T20 (157 x 97 mmHg; P<0.0001), T30 (140 x 67 mmHg; P=0.0001), T45 (117 x 67 mmHg; P=0.002) and T60 (98 x 62 mmHg; P= 0.026). The blood lactate in naloxone group was significantly lower when compared to epinephrine group in the T11 (5.15 x 8.82 mmol/L), T31 (2.57 x 5.24 mmol/L) and T59 (2.1 x 4.1)[P=0.002]. Along the first hour after cardiac arrest, the naloxone group showed the best profile of base excess (- 7.78 mmol/L) when compared to epinephrine (-12.78 mmol/L, P= 0.014) and terlipressin group (-11.31 mmol/L, P=0.024). Conclusions: In this model of CA induced by hypoxia in rats, terlipressin and naloxone were effective as vasopressors in resuscitation and had better metabolic profile compared to epinephrine. Terlipressin resulted in higher hemodynamic stability in the first hour after CA and significantly better than epinephrine or vasopressin. The favorable metabolic effects of naloxone are not explained by the values of MAP

O uso da LDE como veículo para quimioterápicos tem mostrado ser uma boa estratégia para aumentar a eficácia terapêutica dos mesmos. Nesse estudo, a LDE foi empregada como veículo para um derivado lipofílico do metotrexato (MTX), o di-dodecil metotrexato, que foi obtido com rendimento elevado através de reação de esterificação do MTX. O aumento na lipofilicidade do derivado possibilitou incorporação na LDE com rendimento e estabilidade elevados. O IC50 de LDE-di-dodecil MTX foi cerca de 100 vezes menor em relação ao MTX comercial, sua captação celular mais elevada nas linhagens leucêmicas estudadas e sua toxicidade animal reduzida, mostrando que a LDE é um veículo promissor para este fármaco. / The use of LDE as vehicle to drugs is a great strategy to improve the therapeutic index and reduce the side effects. In this study LDE was used as vehicle to di-dodecyl methotrexate, a lipophilic derivative of MTX, obtained through an esterification reaction with a high yield. The increased lipophilicity of the derivative allowed a high association to LDE and good stability. The IC50 of LDE-di-dodecyl MTX was lower than that of the MTX and the uptake was higher in leukemic cells. The MTX toxicity in mice was reduced after association to LDE, showing that LDE is a promising vehicle to this drug.

Lau Yin Kei. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 58-79). / Abstracts in English and Chinese. / Acknowledgement --- p.I / Abstract --- p.IV / Abstract in Chinese --- p.VI / Abbreviations --- p.VIII / Introduction --- p.1 / Chapter 1.1 --- Prevalence of COPD and asthma in Hong Kong --- p.1 / Chapter 1.2 --- Players in pathogenesis of COPD --- p.2 / Chapter 1.3 --- Players in pathogenesis of asthma --- p.4 / Chapter 1.4 --- The use of exhaled breath condensate in previous studies --- p.6 / Chapter 1. 5 --- Brief overview of chemokines --- p.8 / Chapter 1.6 --- Objective of this study --- p.12 / Materials and methods --- p.14 / Chapter 2.1 --- Study population --- p.14 / Chapter 2.1.1 --- Patients with COPD and control subjects --- p.14 / Chapter 2.1.2 --- Patients with asthma and control subjects --- p.15 / Chapter 2.2 --- Lung function --- p.15 / Chapter 2.3 --- Dyspnoea score measurement of patients with COPD --- p.16 / Chapter 2.4 --- Classification of patients and asthma severity --- p.16 / Chapter 2.5 --- Skin prick test and blood tests --- p.16 / Chapter 2.6 --- Collection of exhaled breath condensate --- p.17 / Chapter 2.7 --- Measurement of constituent in EBC --- p.17 / Chapter 2.7.1 --- "Measurement of 8-isoprostane, MCP-1 and GROα in patients with COPD and the corresponding control subjects" --- p.17 / Chapter 2.7.2 --- Measurement of eotaxin and MDC of patients with asthma and the corresponding control subjects --- p.18 / Chapter 2.8 --- Reproducibility of exhaled breath constituent --- p.18 / Chapter 2.8.1 --- "Assessment of reproducibility of the exhaled MCP-1, GROα and8- isoprostane measurements" --- p.19 / Chapter 2.8.2 --- Assessment of reproducibility of the exhaled eotaxin and MDC measurement --- p.19 / Chapter 2.9 --- Statistical analysis --- p.19 / Results --- p.21 / Chapter 3.1 --- Patients with COPD and corresponding control subjects --- p.21 / Chapter 3.2 --- Patients with asthma and corresponding control subjects --- p.28 / Discussion --- p.36 / Chapter 4.1 --- "Exhaled 8-isoprostane, GRO-α and MCP-1 of patients with COPD and corresponding control subjects" --- p.36 / Chapter 4.2 --- Exhaled eotaxin and MDC from patients with asthma and corresponding control subjects --- p.43 / Chapter 4.3 --- Technical aspects of EBC assessment --- p.49 / Future prospect --- p.54 / Conclusion --- p.56 / References --- p.58 / Tables and Figures / Table 1. Demographics of the COPD and control subjects --- p.22 / Figure 1. The level of 8-isoprostane in the exhaled breath condensate of COPD and control subjects --- p.23 / Figure 2. The level of GROa in the exhaled breath condensate of COPD and control subjects --- p.25 / "Figure 3 Bland and Altman's Plot of the repeatability of 8-isoprostane, GROa and MCP-1 in the exhaled breath condensate of normal controls" --- p.27 / Table2. Clinical and physiological details of the subjects --- p.29 / Figure 4. Level of eotaxin in exhaled breath condensate of asthma and control subjects --- p.30 / Figure 5 Level of MDC in exhaled breath condensate of asthma and control subjects --- p.31 / Table 3. Levels of eotaxin and MDC in exhaled breath condensate of asthma subjects on different dose of inhaled corticosteroids --- p.33 / Figure 6. Relationship between exhaled breath condensate level of MDC and total serum IgE level --- p.35

Chan Ho Yee. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 121-138). / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.II / ABSTRACT --- p.III / 摘要 --- p.V / ABBREVIATIONS --- p.VI / "TABLE OF CONTENTS, " --- p.VII / LIST OF FIGURES AND TABLES --- p.XI / Chapter CHAPTER 1 --- GENERAL INTRODUCTION --- p.1 / Xenobiotic-metabolizing enzymes --- p.1 / Cytochrome P450 1 family --- p.4 / CYP1A1 --- p.5 / CYP1A2 --- p.5 / CYP1B1 --- p.5 / Transactivation of CYP1 enzymes by Aryl hydrocarbon receptor (AhR) --- p.8 / Implication of PAHs and CYP1 family in breast cancer --- p.10 / Potential role of phytochemicals on cancer prevention --- p.11 / Significance of this project --- p.13 / Chapter CHAPTER 2 --- MATERIALS AND METHODS --- p.14 / Chemicals --- p.14 / Maintenance of cells --- p.14 / Preparation of cell stock --- p.14 / Cell recovery from liquid nitrogen stock --- p.15 / Measurement of cell viability --- p.15 / Preparation of cell lysates (NP-40 cell lysis buffer) --- p.15 / XRE-luciferase gene reporter assay --- p.16 / Manipulation of DNA and RNA --- p.17 / Separation and purification of DNA from agarose gel --- p.17 / Separation of DNA from acrylamide gel --- p.17 / Restriction digestion --- p.18 / Ligation of DNA fragments --- p.18 / Transformation of DH5 a --- p.19 / Small scale plasmid purification from DH5a (mini prep) --- p.19 / Large scale plasmid isolation from DH5a (maxi-prep) --- p.20 / Construction of XRE activated luciferase reporter gene --- p.21 / Measurement of DMBA-DNA adduct formation --- p.21 / Semi-quantitative RT-PCR Assay --- p.22 / ENZYME ACTIVITIES --- p.23 / Isolation of microsomes --- p.23 / EROD activities in intact cells --- p.23 / EROD inhibition assay --- p.24 / Stattstical Analysis --- p.24 / Chapter CHAPTER 3 --- BAICALEIN INHIBITS DMBA-DNA ADDUCT FORMATION BY MODULATING CYP1A1 AND 1B1 ACTIVITIES --- p.26 / Introduction --- p.26 / Results --- p.28 / EROD activities in MCF-7 cells and inhibition assay --- p.28 / Baicalein suppressed DMBA-induced XRE-driven luciferase activities --- p.31 / Baicalein inhibited DMBA-induced CYP1A1 and CYP1B1 mRNA expression --- p.31 / The cytotoxic effect of DMBA was reduced by baicalein --- p.35 / Inhibition of DMBA-DNA adduct formation after baicalein treatment --- p.35 / Discussion --- p.39 / Chapter CHAPTER 4 --- INHIBITION OF DMBA-DNA ADDUCT FORMATION BY (-)-EPIGALLOCATECHIN GALLATE AND THEAFLAVINS --- p.41 / Introduction --- p.41 / Results --- p.45 / Persistence of DMBA-induced DNA adducts --- p.45 / Inhibition of theaflavins and EGCG on human recombinant CYP1A1 and CYP1B1 enzyme activities --- p.48 / EGCG suppressed DMBA-induced EROD activity while thealfavin had no significant effect on this --- p.48 / Kinetic analysis of EGCG on CYP1A1 and CYP1B1 activities --- p.53 / Modulation of DMBA-induced XRE-driven luciferase activities by theaflavins and EGCG --- p.56 / The influence of theaflavins and EGCG on CYP1A1 and CYP1B1 abundance --- p.56 / Discussion --- p.65 / Chapter CHAPTER 5 --- ISOFLAVONES PREVENT DMBA-INDUCED CARCINOGENESIS BY INHIBITING CYP1A1 AND CYP1B1 ACTIVITIES --- p.67 / Introduction --- p.67 / Results --- p.70 / Isoflavones inhibited DMBA-induced EROD activity in MCF-7 cells --- p.70 / Inhibition of MCF-7 microsomal EROD activities by isoflavones --- p.70 / Kinetic analysis of the inhibition of human recombinant CYP1 enzymes by isoflavones --- p.74 / XRE-driven Luciferase activities --- p.83 / Both biochanin A and genistein suppressed DMBA-induced CYP1 mRNA expression --- p.83 / Cytotoxicity of DMBA and isoflavones co-treatment --- p.88 / Isoflavones reduced the binding of activated DMBA to DNA --- p.89 / Discussion --- p.93 / Chapter CHAPTER 6 --- IN VITRO EFFECTS OF BAICALEIN AND THEAFLAVINS ON RAT HEPATIC P450 ACTIVITIES --- p.96 / Introduction --- p.96 / Results --- p.98 / Inhibition of EROD and MROD activities in rat liver microsomes by baicalein --- p.98 / Effects of theaflavins on EROD and MROD activities in rat liver microsomes --- p.102 / Kinetic studies for EROD and MROD activities of theaflavins --- p.104 / DISCUSSION --- p.114 / Chapter CHAPTER 7 --- CONCLUSION --- p.116 / APPENDIX 1 PRIMER LISTS --- p.118 / APPENDIX 2 REAGENTS --- p.119 / BIBLIOGRAPHY --- p.121

Introdução: O prognóstico da parada cardiorrespiratória (PCR) em ritmo não chocável (assistolia/atividade elétrica sem pulso) é ruim e não melhorou significativamente nas últimas décadas. Embora a epinefrina seja o vasopressor recomendado, há evidências de que ela eleva o consumo de oxigênio, reduz a pressão de perfusão subendocárdica, causa grave disfunção miocárdica e piora a microcirculação cerebral durante a ressuscitação cardiopulmonar. Vasopressina foi muito estudada nos últimos anos e não se mostrou superior à epinefrina. Naloxona e terlipressina têm sido cogitadas como potenciais vasopressores no tratamento da PCR, entretanto há poucos estudos publicados e os resultados são controversos e inconclusivos. Objetivos: Avaliar os efeitos hemodinâmicos e metabólicos da terlipressina ou naloxona na PCR induzida por hipóxia e compará-las com o tratamento-padrão (epinefrina ou vasopressina). Métodos: Estudo experimental, randomizado, cego e controlado. Ratos Wistar adultos, machos, foram anestesiados, submetidos a traqueostomia e ventilados mecanicamente. A PCR foi induzida por obstrução da traqueia e mantida por 3,5 minutos. Em seguida, os animais foram ressuscitados de forma padronizada e randomizados em um dos grupos: placebo (n = 7), vasopressina (n = 7), epinefrina (n = 7), naloxona (n = 7) ou terlipressina (n = 21). Variáveis hemodinâmicas foram monitorizadas durante todo o experimento (via cateter intra-arterial e intraventricular) e mensuradas na base, no 10o (T10), 20o (T20), 30o (T30), 45o (T45) e 60o (T60) minutos pós-PCR. Amostras de sangue arterial foram coletadas para gasometria, hemoglobina, bioquímica e lactato em quatro momentos [base, 11o (T11), 31o (T31), e 59o (T59) minutos pós-PCR]. Resultados: Os grupos foram homogêneos e não houve diferença significativa entre eles nas variáveis de base. O retorno da circulação espontânea ocorreu em 57% dos animais no grupo placebo (4 de 7) e 100% nos demais grupos (p = 0,002). A ! sobrevida em 1 hora foi de 57% no grupo placebo, 71,4% no grupo epinefrina, 90,5% no grupo terlipressina e de 100% nos demais grupos. Comparado com o grupo epinefrina, o grupo terlipressina teve maiores valores de PAM no T10 (164 vs 111 mmHg; p = 0,02), T20 (157 vs 97 mmHg; p < 0,0001), T30 (140 vs 67 mmHg; p < 0,0001), T45 (117 vs 67 mmHg; p = 0,002) e T60 (98 vs 62 mmHg; p = 0,026). O lactato arterial no grupo naloxona foi significativamente menor quando comparado ao grupo epinefrina, no T11 (5,15 vs 8,82 mmol/L), T31 (2,57 vs 5,24 mmol/L) e T59 (2,1 vs 4,1 mmol/L)[p = 0,002]. Ao longo da 1a hora pós-PCR, o grupo naloxona apresentou o melhor perfil do excesso de bases (-7,78 mmol/L) quando comparado ao grupo epinefrina (-12,78 mmol/L; p = 0,014) e ao grupo terlipressina (-11,31 mmol/L; p = 0,024). Conclusões: Neste modelo de PCR induzida por hipóxia em ratos, terlipressina e naloxona foram eficazes como vasopressores na RCP e apresentaram melhor perfil metabólico que a epinefrina. A terlipressina resultou em uma maior estabilidade hemodinâmica na 1a hora pós-PCR comparada com a epinefrina ou a vasopressina. Os efeitos metabólicos favoráveis da naloxona não são explicados pelos valores da PAM / Introduction: The prognosis of cardiac arrest (CA) with nonshockable rhythm (asystole/pulseless electrical activity) is poor and not improved significantly in recent decades. Epinephrine is the most commonly used vasopressor, although there is evidence that its use correlates with myocardial dysfunction and worsens the cerebral microcirculation. Vasopressin has been widely studied in recent years and was not superior to epinephrine. Naloxone and terlipressin have been considered as potential vasopressors in the treatment of CA, however, there are few published studies and the results are controversial and inconclusive. Objectives: To evaluate the hemodynamic and metabolic effects of terlipressin or naloxone in CA induced by hypoxia and compare with standard treatment with epinephrine or vasopressin. Methods: Experimental, randomized, blinded and controlled trial. Adult male Wistar rats were anesthetized, the proximal trachea was surgically exposed, and a 14-gauge cannula was inserted 10 mm into the trachea to the larynx. They were mechanically ventilated and monitored. The CA was induced by tracheal obstruction and maintained for 3.5 minutes. Subsequently, the animals were resuscitated using standard maneuvers and randomized to one of groups: placebo (n=7), vasopressin (n=7), epinephrine (n=7), naloxone (n=7) or terlipressin (n=21). Hemodynamic variables were monitored throughout the study (intra-arterial and intra-ventricular catheter) and measured at baseline, in the 10th (T10), 20th (T20), 30th (T30), 45th (T45) and 60th (T60) minute post-cardiac arrest. Arterial blood samples were collected for hemoglobin, biochemistry, blood gases and lactate at four moments: baseline, 11th (T11), 31st (T31) and 59th (T59) minute post-cardiac arrest. Results: The groups were homogenous and there were no significant differences among them regarding the baseline variables. The return of spontaneous circulation (ROSC) occurred in 57% of the animals (4 of 7) in the placebo group and in 100% in the ! other groups (P=0.002). One-hour survival was 57% in the placebo group, 71.4% in the epinephrine group, 90.5% in the terlipressin and 100% in the naloxone group. Compared with the epinephrine group, the terlipressin groups had a significantly higher MAP at the T10 (164 x 111 mmHg; P=0.02), T20 (157 x 97 mmHg; P<0.0001), T30 (140 x 67 mmHg; P=0.0001), T45 (117 x 67 mmHg; P=0.002) and T60 (98 x 62 mmHg; P= 0.026). The blood lactate in naloxone group was significantly lower when compared to epinephrine group in the T11 (5.15 x 8.82 mmol/L), T31 (2.57 x 5.24 mmol/L) and T59 (2.1 x 4.1)[P=0.002]. Along the first hour after cardiac arrest, the naloxone group showed the best profile of base excess (- 7.78 mmol/L) when compared to epinephrine (-12.78 mmol/L, P= 0.014) and terlipressin group (-11.31 mmol/L, P=0.024). Conclusions: In this model of CA induced by hypoxia in rats, terlipressin and naloxone were effective as vasopressors in resuscitation and had better metabolic profile compared to epinephrine. Terlipressin resulted in higher hemodynamic stability in the first hour after CA and significantly better than epinephrine or vasopressin. The favorable metabolic effects of naloxone are not explained by the values of MAP

O uso da LDE como veículo para quimioterápicos tem mostrado ser uma boa estratégia para aumentar a eficácia terapêutica dos mesmos. Nesse estudo, a LDE foi empregada como veículo para um derivado lipofílico do metotrexato (MTX), o di-dodecil metotrexato, que foi obtido com rendimento elevado através de reação de esterificação do MTX. O aumento na lipofilicidade do derivado possibilitou incorporação na LDE com rendimento e estabilidade elevados. O IC50 de LDE-di-dodecil MTX foi cerca de 100 vezes menor em relação ao MTX comercial, sua captação celular mais elevada nas linhagens leucêmicas estudadas e sua toxicidade animal reduzida, mostrando que a LDE é um veículo promissor para este fármaco. / The use of LDE as vehicle to drugs is a great strategy to improve the therapeutic index and reduce the side effects. In this study LDE was used as vehicle to di-dodecyl methotrexate, a lipophilic derivative of MTX, obtained through an esterification reaction with a high yield. The increased lipophilicity of the derivative allowed a high association to LDE and good stability. The IC50 of LDE-di-dodecyl MTX was lower than that of the MTX and the uptake was higher in leukemic cells. The MTX toxicity in mice was reduced after association to LDE, showing that LDE is a promising vehicle to this drug.