LIPOXYGENASE-DERIVED MEDIATORS MAY BE INVOLVED IN IN-VIVO NEUTROPHIL MIGRATION INDUCED BY BOTHROPS ERYTHROMELAS AND BOTHROPS ALTERNATUS VENOMS

Bothrops erythromelas (BEV) and B. alternatus (BAV) venoms induced a dose-dependent neutrophil migration when injected into rat peritoneal cavities (20-160 mu g/cavity). These venoms (80 mu g/rat) also induced neutrophil migration in the air pouch model of inflammation. This migratory response seemed to be related to the phospholipase A(2) (PLA(2)) activity of the venoms. BAV had approximately two times more PLA(2) activity than BEV, and the neutrophil migration induced by the former venom was two to three-fold greater than that observed with the latter. Heated (90 degrees C for 5 min) BEV lost about 50% of its PLA(2) activity and this was accompanied by a corresponding loss in the ability to induce neutrophil chemotaxis. Dexamethasone (0.5 mg/kg, s.c.), an indirect inhibitor of PLA(2) activity, also abolished the neutrophil migration induced by both venoms. Since NDGA (100 mg/kg, s.c.) and dexamethasone, but not indomethacin (2 mg/kg, s.c.), strongly reduced the neutrophil migration induced by both bothropic venoms, it is suggested that arachidonate-derived lipoxygenase metabolites such as leukotriene B-4 act as the chemotactic mediators. Macrophages could be the main cellular source of such metabolites since they are the predominant resident cells in the rat air pouch, and the migratory response of BEV and BAV into peritoneal cavities was potentiated in rats pretreated with thioglycollate. The neutrophil migration induced by BEV and BAV was not due to endotoxin contamination since heated BEV showed no effect and polymyxin B-treated BAV still remained active.31121551155

A method for the evalutation of the frequencies of incidental events related to the ships traffic inside a port using a statistical approach

Aim of this paper is to present a semi-probabilistic, semi-deterministic methodology to evaluate the risk of dangerous spills, and related public and environmental hazard, associated to the navigation in a narrow channel-port. The model is based on a Monte Carlo method with variance reduction technique and can simulate different kinds of ship (tonnage, carried substance) and different kinds of routes to reach or to leave the jetties and the port. The basic event probability (operating error) can evolve in collision with: other flowing or moored ships, sand banks, free jetties, dangerous structures. The possible consequences can be spills of hazardous materials, In addition, the probabilistic model evaluates the frequencies of the events at jetty, as onboard fire and/or explosion, load or unload and berth or unberth accidents. The simulation of the system in study can be performed automatically by a package of two programs: the first (input module) accepts the topological and traffic information about the port; the second (simulation module) simulates the port and the traffic using the inputs created by the first. The simulation program can handle sensitivity analysis. Finally, the methodology has been applied to an idealised but realistic situation of channel-por

Lipoxygenase-derived Mediators May Be Involved In In Vivo Neutrophil Migration Induced By Bothrops Erythromelas And Bothrops Alternatus Venoms.

Bothrops erythromelas (BEV) and B. alternatus (BAV) venoms induced a dose-dependent neutrophil migration when injected into rat peritoneal cavities (20-160 micrograms/cavity). These venoms (80 micrograms/rat) also induced neutrophil migration in the air pouch model of inflammation. This migratory response seemed to be related to the phospholipase A2 (PLA2) activity of the venoms. BAV had approximately two times more PLA2 activity than BEV, and the neutrophil migration induced by the former venom was two to three-fold greater than that observed with the latter. Heated (90 degrees C for 5 min) BEV lost about 50% of its PLA2 activity and this was accompanied by a corresponding loss in the ability to induce neutrophil chemotaxis. Dexamethasone (0.5 mg/kg, s.c.), an indirect inhibitor of PLA2 activity, also abolished the neutrophil migration induced by both venoms. Since NDGA (100 mg/kg, s.c.) and dexamethasone, but not indomethacin (2 mg/kg, s.c.), strongly reduced the neutrophil migration induced by both bothropic venoms, it is suggested that arachidonate-derived lipoxygenase metabolites such as leukotriene B4 act as the chemotactic mediators. Macrophages could be the main cellular source of such metabolites since they are the predominant resident cells in the rat air pouch, and the migratory response of BEV and BAV into peritoneal cavities was potentiated in rats pretreated with thioglycollate. The neutrophil migration induced by BEV and BAV was not due to endotoxin contamination since heated BEV showed no effect and polymyxin B-treated BAV still remained active.311551-

Lipoxygenase-derived Mediators May Be Involved In In Vivo Neutrophil Migration Induced By Bothrops Erythromelas And Bothrops Alternatus Venoms

Bothrops erythromelas (BEV) and B. alternatus (BAV) venoms induced a dose-dependent neutrophil migration when injected into rat peritoneal cavities (20-160 μg/cavity). These venoms (80 μg/rat) also induced neutrophil migration in the air pouch model of inflammation. This migratory response seemed to be related to the phospholipase A2 (PLA2) activity of the venoms. BAV had approximately two times more PLA2 activity than BEV, and the neutrophil migration induced by the former venom was two to three-fold greater than that observed with the latter. Heated (90°C for 5 min) BEV lost about 50% of its PLA2 activity and this was accompanied by a corresponding loss in the ability to induce neutrophil chemotaxis. Dexamethasone (0.5 mg/kg, s.c.), an indirect inhibitor of PLA2 activity, also abolished the neutrophil migration induced by both venoms. Since NDGA (100 mg/kg, s.c.) and dexamethasone, but not indomethacin (2 mg/kg, s.c.), strongly reduced the neutrophil migration induced by both bothropic venoms, it is suggested that arachidonate-derived lipoxygenase metabolites such as leukotriene B4 act as the chemotactic mediators. Macrophages could be the main cellular source of such metabolites since they are the predominant resident cells in the rat air pouch, and the migratory response of BEV and BAV into peritoneal cavities was potentiated in rats pretreated with thioglycollate. The neutrophil migration induced by BEV and BAV was not due to endotoxin contamination since heated BEV showed no effect and polymyxin B-treated BAV still remained active. © 1993.311215511559Assakura, Reichl, Asperti, Mandelbaum, Isolation of the major proteolytic enzyme from the venom of the snakeBothrops moojeni (caissaca) (1985) Toxicon, 23, pp. 691-706Basavarajappa, Gowda, Comparative characterization of two toxic phospholipases A2 from Indian cobra(Naja naja naja) venom (1992) Toxicon, 30, pp. 1227-1238Dinarello, Cytokines: interleukin-1 and tumor necrosis factor (cachectin) (1988) Inflammation: Basic Principles and Clinical Correlates, pp. 195-208. , J.I. Gallin, I.M. Goldstein, R. Snyderman, Raven Press, New YorkFaccioli, Souza, Cunha, Poole, Ferreira, Recombinant interleukin-1 and tumor necrosis factor induce neutrophil migrationin vivo by indirect mechanisms (1990) Agents Actions, 30, pp. 344-349Ferreira, Are macrophages the body's alarm cells? (1980) Agents Actions, 10, p. 229Flower, Glucocorticoids and the inhibition of phospholipase A2 (1989) Antiinflammatory Steroid Action. Basic and Clinical Aspects, pp. 48-66. , R.P. Schleimer, H.N. Clamor, A.L. Oronsky, Academic Press, New YorkFoster, McCormick, Howarth, Aked, Leukocyte recruitment in the sub-cutaneous sponge implant model of acute inflammation in the rat is not mediated by leukotriene B4 (1986) Biochem. Pharmac., 35, pp. 1709-1717Gutierrez, Lomonte, Local tissue damage induced byBothrops snake venoms (1989) A review, 51, pp. 211-223. , Mem. Inst. ButantanGutierrez, Chaves, Mata, Cerdas, Skeletal muscle regeneration after myonecrosis induced byBothrops asper (terciopelo) venom (1986) Toxicon, 24, pp. 223-231Higgs, Moncada, Vane, Eicosanoids in inflammation (1984) Ann. clin. Res., 16, pp. 287-299Kaiser, Michl, Chemistry and pharmacology of the venoms ofBothrops andLachesis (1971) Venomous Animals and their Venoms, 2, pp. 307-318. , W. Bucherl, E.E. Buckley, Academic Press, New YorkKini, Evans, A model to explain the pharmacological effects of snake venom phospholipase A2 (1989) Toxicon, 27, pp. 613-635Lewis, Austen, Leukotrienes (1988) Inflammation: Basic Principles and Clinical Correlates, pp. 121-128. , J.I. Gallin, I.M. Goldstein, R. Snyderman, Raven Press, New YorkLoˆbo de Arau´jo, Radvanyi, Determination of phospholipase A2 activity by a colorimetric assay using a pH indicator (1987) Toxicon, 25, pp. 1181-1188Mandelbaum, Reichl, Assakura, Some physical and biochemical characteristics of HF2, one of the hemorrhagic factors in the venom ofBothrops jararaca (1976) Animal, Plant and Microbial Toxins, 1, pp. 111-121. , A. Oshaka, K. Hayashi, Y. Saway, Plenum Press, LondonMandelbaum, Assakura, Reichl, Characterization of two hemorrhagic factors isolated from the venom ofBothrops neuwiedi (jararaca pintada) (1984) Toxicon, 22, pp. 193-206McManus, Pathobiology of platelet-activating factor (1986) Path. Immunopath. Res., 5, pp. 104-117Nakamura, Ferreira, Peripheral sympathetic component in inflammatory hyperalgesia (1987) Eur. J. Pharmac., 135, pp. 145-153Nathan, Secretory products of macrophages (1987) J. clin. Invest., 79, pp. 319-324Ribeiro, Flores, Cunha, Ferreira, IL-8 causesin vivo neutrophil migration by a cell-dependent mechanism (1991) Immunology, 73, pp. 472-477Rosenfeld, Symptomatology, pathology and treatment of snake bites in South America (1971) Venomous Animals and their Venoms, 2, pp. 345-403. , W. Bucherl, E.E. Buckley, Academic Press, New YorkRothschild, Rothschild, Liberation of pharmacologically active substances by snake venoms (1979) Snake Venoms. Handbood of Experimental Pharmacology, 52, pp. 591-628. , C.Y. Lee, Springer, BerlinSouza, Ferreira, Blockade by antimacrophage serum of the migration of PMN-neutrophils into the inflamed peritoneal cavity (1985) Agents Actions, 17, pp. 97-102Tateson, Randall, Reynolds, Jackson, Bhattacherjee, Salmon, Garland, Selective inhibition of arachidonate 5-lipoxygenase by novel acetohydroxamic acids: biochemical assessmentin vitro andex vivo (1988) Br. J. Pharmac., 94, pp. 528-539Trebien, Calixto, Pharmacological evaluation of rat paw oedema induced byBothrops jararaca venom (1989) Agents Actions, 26, pp. 292-300Weisman, Bartow, Leppo, Marsh, Jr, Carson, Concino, Boyle, Fearon, Soluble human complement receptor type 1:in vivo inhibitor of complement suppressing post-ischemic myocardial inflammation and necrosis (1990) Science, 249, pp. 146-15

Evaluation of two different oxygen inspiratory fractions on the hemodynamic effects of N-omega-nitro-L-arginine methyl ester in anesthetized dogs

The effect of two different oxygen inspiratory fractions (FiO(2)=21% and 100%) on the hemodynamic responses induced by N(o)mega-nitro-L-arginine methyl ester (L-NAME) was investigated in anesthetized dogs. L-NAME (0.01-10.0mg/kg), but not D-NAME: induced dose-dependent changes in the hemodynamic parameters of the animals. At the highest dose, L-NAME increased mean arterial blood pressure in both room air (from 86.2-/+3.2 to 125.1-/+7.8 mmHg) and pure oxygen (from 100.0-/+7.5 to 139.0-/+3.2 mmHg) ventilated animals. L-NAME also increased systemic and pulmonary vascular resistances. These effects were accompanied by a decrease in cardiac output and bradycardia (37% and 31% decreases far pure oxygen and room air, respectively). However, there were no significant differences in the responses to L-NAME between the dogs ventilated with FiO(2)=21% and those ventilated with FiO(2)= 100%. L-NAME did not modify blood gas analyses, despite the expected difference in pO(2) levels between the two experimental groups of animals (3 times higher in the animals ventilated with pure oxygen). These results indicate that nitric oxide release accounts for the maintenance of hemodynamic function in the anesthetized dog, and that L-NAME-induced effects are not affected by hyperoxemiaAssociação Brasileira de Divulgação Científica2913339BrasilBrazilian journal of medical and biological researchBrazilian J. med. biol. res.São Paulo, S

Evaluation of two different oxygen inspiratory fractions on the hemodynamic effects of N omega-nitro-l-arginine methyl ester in anesthetized dogs

The effect of two different oxygen inspiratory fractions (FiO2 = 21% and 100%) on the hemodynamic responses induced by N omega-nitro-L-arginine methyl ester (L-NAME) was investigated in anesthetized dogs. L-NAME (0.01-10.0 mg/kg), but not D-NAME, induced dose-dependent changes in the hemodynamic parameters of the animals. At the highest dose, L-NAME increased mean arterial blood pressure in both room air (from 86.2 +/- 3.2 to 125.1 +/- 7.8 mmHg) and pure oxygen (from 100.0 +/- 7.5 to 139.0 +/- 3.2 mmHg) ventilated animals. L-NAME also increased systemic and pulmonary vascular resistances. These effects were accompanied by a decrease in cardiac output and bradycardia (37% and 31% decreases for pure oxygen and room air, respectively). However, there were no significant differences in the responses to L-NAME between the dogs ventilated with FiO2 = 21% and those ventilated with FiO2 = 100%. L-NAME did not modify blood gas analyses, despite the expected difference in pO2 levels between the two experimental groups of animals (3 times higher in the animals ventilated with pure oxygen). These results indicate that nitric oxide release accounts for the maintenance of hemodynamic function in the anesthetized dog, and that L-NAME-induced effects are not affected by hyperoxemia.The effect of two different oxygen inspiratory fractions (FiO2 = 21% and 100%) on the hemodynamic responses induced by N omega-nitro-L-arginine methyl ester (L-NAME) was investigated in anesthetized dogs. L-NAME (0.01-10.0 mg/kg), but not D-NAME, induced dose-dependent changes in the hemodynamic parameters of the animals. At the highest dose, L-NAME increased mean arterial blood pressure in both room air (from 86.2 +/- 3.2 to 125.1 +/- 7.8 mmHg) and pure oxygen (from 100.0 +/- 7.5 to 139.0 +/- 3.2 mmHg) ventilated animals. L-NAME also increased systemic and pulmonary vascular resistances. These effects were accompanied by a decrease in cardiac output and bradycardia (37% and 31% decreases for pure oxygen and room air, respectively). However, there were no significant differences in the responses to L-NAME between the dogs ventilated with FiO2 = 21% and those ventilated with FiO2 = 100%. L-NAME did not modify blood gas analyses, despite the expected difference in pO2 levels between the two experimental groups of animals (3 times higher in the animals ventilated with pure oxygen). These results indicate that nitric oxide release accounts for the maintenance of hemodynamic function in the anesthetized dog, and that L-NAME-induced effects are not affected by hyperoxemia291333

Small-dose Inhaled Nitric Oxide Attenuates Hemodynamic Changes After Pulmonary Air Embolism In Dogs.

Inhaled nitric oxide (NO) has been used to treat pulmonary hypertension. Experimental studies have suggested therapeutic effects of NO after pulmonary microembolism. We evaluated the protective effects of NO in dogs during a pulmonary air embolism (PAE). NO (3 ppm) was administered to six anesthetized mongrel dogs (NO group) but not to the seven dogs in the control group. After 20 min, each dog received a venous air injection of 2.5 mL/kg. Hemodynamic evaluation was performed, and blood samples were drawn for blood gas analysis before and after NO inhalation and 5-60 min after the PAE. Both arterial blood pressure and cardiac output were decreased in the control group for >15 min after PAE, whereas NO-treated animals showed only transient hypotension. NO attenuated the pulmonary hypertension after PAE, as demonstrated by small (P < 0.05) increases in pulmonary artery pressure and pulmonary vascular resistance index in NO-treated animals (90% and 135%, respectively) compared with the controls (196% and 282%, respectively). These hemodynamic effects of NO were associated with higher mixed venous O2 tensions and saturations in the NO group compared with the controls. We conclude that small-dose NO (3 ppm) attenuated the hemodynamic changes induced by PAE in dogs. This protective effect of NO on hemodynamics is not accompanied by improvement in pulmonary oxygenation in this setting. In this study, we evaluated the protective effects of inhaled nitric oxide in a pulmonary air embolism setting. Nitric oxide attenuated the hemodynamic changes induced by pulmonary air embolism without improving pulmonary oxygenation.881025-

ALTERATIONS IN RAT CARBOHYDRATE-METABOLISM INDUCED BY CANATOXIN AS A PROBABLE CONSEQUENCE OF PRIMARY HYPOXIA

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