PubMed Health⌕ Search

Biomedical subjects

D Altavilla

Publications and source records attributed to D Altavilla.

At least 91 records · Page 5Linked to original sources
PubMed1992

Passive immunization with antibodies against tumor necrosis factor (TNF-alpha) protects from the lethality of splanchnic artery occlusion shock.

Splanchnic artery occlusion shock was induced in anesthetized rats by clamping splanchnic arteries for 45 min. Survival rate, serum and macrophage tumor necrosis factor (TNF-alpha), peritoneal macrophage phagocytosis, and killing activities were evaluated. Shocked rats died within 2 hr, whilst all sham-shocked rats survived more than 6 hr. Serum and macrophage TNF-alpha was undetectable in sham-shocked rats while shocked rats exhibited increased serum (110 +/- 5 U/ml 90 min after release of occlusion) and macrophage levels (122 +/- 4.5 U/ml 90 min after release of occlusion) of TNF-alpha. Furthermore, splanchnic artery occlusion shock produced cardiovascular changes, reduced macrophage phagocytosis (23 +/- 4.6%) and killing (6 +/- 1.1%) activities, and induced a massive necrosis of the ileum. A passive immunization with a hyperimmune serum containing antibodies against murine TNF-alpha significantly protected rats from the lethal effects of splanchnic artery occlusion shock, lowered serum TNF-alpha (6 +/- 2.1 U/ml), and completely reverted the impairment in peritoneal macrophage phagocytosis (48 +/- 4.8%) and killing (13 +/- 1.5%) activities. In addition passive immunization had beneficial effects on the cardiovascular changes occurring during splanchnic artery occlusion shock and prevented necrosis of the ileum induced by this model of shock. By contrast, pretreatment with polymyxin B, an "antiendotoxin" antibiotic, did not modify the lethal effects and the TNF-alpha production induced by splanchnic artery occlusion shock. Furthermore, endotoxin was undetectable in the blood of splanchnic artery occlusion shocked rats. These findings are consistent with the involvement of TNF-alpha in splanchnic artery occlusion shock and suggest that the cytokine represents an important mediator of non-septic shock.

Animals↗
PubMed1991

Platelet activating factor involvement in splanchnic artery occlusion shock in rats.

Splanchnic artery occlusion shock was induced in anesthetized rats by clamping the splanchnic arteries for 45 min. The survival rate, plasma levels of thromboxane B2 (TxB2) and 6-keto-PGF1 alpha, serum and peritoneal levels of macrophage tumor necrosis factor (TNF alpha), the phagocytotic and killing activity of peritoneal macrophages and white blood cells count were evaluated. Shocked rats died within 2 h, while all sham-shocked rats survived more than 6 h. Plasma TxB2 and 6-keto-PGF1 alpha levels were increased in rats subjected to splanchnic artery occlusion shock compared to the levels in sham-shocked animals. Serum and peritoneal macrophage TNF alpha levels were undetectable in sham-shocked rats, whereas shocked rats exhibited increased levels of TNF alpha. Moreover, splanchnic artery occlusion shock reduced peritoneal macrophage phagocytotic and killing activity, and also produced severe leukopenia. A specific receptor antagonist of platelet activating factor (PAF), L-652, 731 (an i.v. bolus of 3.2 mg/kg 2 min after removal of the clamps followed, 5 min thereafter, by a continuous infusion of 0.16 mg/kg per min for 30 min) significantly increased the survival rate, lowered plasma TxB2 levels and reduced both serum and macrophage TNF alpha levels in shocked rats. In addition, L-652,731 completely restored macrophage phagocytosis, partially improved macrophage killing and significantly inhibited leukopenia. Finally, the administration of L-652,731 had beneficial effects on the cardiovascular changes induced by splanchnic artery occlusion shock. These findings are consistent with the involvement of PAF in splanchnic artery occlusion shock and indicate that PAF produces shock through direct and indirect (TxB2-mediated and TNF alpha-mediated) actions.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Effects of fructose 1,6-diphosphate on splanchnic artery occlusion shock in the rat.

Splanchnic artery occlusion (SAO) shock, produced by clamping splanchnic arteries for 45 min followed by the release of occlusion, was induced in male rats, treated 15 min before surgery, with fructose 1,6-diphosphate (FDP) or with equivalent doses of fructose or inorganic phosphate. Survival rate, peritoneal macrophage phagocytosis and plasma levels of myocardial depressant factor (MDF) were measured. Shocked animals pretreated with vehicle exhibited 24.6 +/- 0.9% phagocytic activity, 110 +/- 3.9 units/ml MDF plasma levels and 0% survival. Sham animals showed the following values: survival 100%; phagocytosis, 49.5 +/- 1.3%; MDF, 22 +/- 2.9 units/ml. Pretreatment with FDP (25 mg/kg/i.v.) significantly improved survival rate (50%) and macrophage phagocytosis (37.9 +/- 0.4%) and reduced plasma MDF levels (77 +/- 3 units/ml). Equivalent doses of fructose and inorganic phosphate did not improve survival, as well as lower doses of FDP. These results suggest a beneficial effect of FDP in SAO shock.

Animals↗
PubMed1989

Cloricromene improves survival rate and peritoneal macrophage function in splanchnic artery occlusion shock in rats.

Splanchnic artery occlusion (SAO) shock, induced by a transient occlusion of splanchnic arteries for 45 min, was performed in male rats, treated with vehicle or cloricromene, a coumarin derivative, 15 min before surgery. Survival rate, plasma levels of myocardial depressant factor (MDF), macrophage phagocytosis and killing of Candida albicans, and thromboxane B2 (TxB2) synthesis by peritoneal macrophages were evaluated. Of the SAO-shocked animals, 10% survived for 6 hr after the release of the occlusion of the splanchnic arteries, whereas none of the sham-shocked rats died. Peritoneal macrophages of shocked animals exhibited decreased phagocytosis (24.7 +/- 2.7%) and killing (8.0 +/- 2.1%) and increased TxB2 levels (3.23 +/- 0.27 ng/ml) with respect to those collected from sham-shocked animals (phagocytosis 48.8 +/- 3.0%; killing 16.5 +/- 2.4%; TxB2 0.30 +/- 0.18 ng/ml). MDF was also increased (114.3 +/- 21.5 U/ml) compared with sham-shocked animals (31.5 +/- 3.7 U/ml). Cloricromene, given intravenously (i.v.) at doses of 1, 2, and 4 mg/kg, significantly increased survival rate and lowered MDF in shocked rats. Lower doses (0.25 and 0.5 mg/kg/i.v.) were without effect. Doses that were able to reduce mortality partially reverted shock-induced macrophage impairment of phagocytosis, killing of C. albicans, and TxB2 synthesis. In addition, cloricromene (5, 10, and 25 microM) added in vitro to peritoneal macrophages, collected from shocked rats, significantly enhanced their phagocytic activity depressed by shock.

Animals↗
PubMed1988

Effect of bacterial endotoxin on lipoxygenase and cyclo-oxygenase metabolites by rat neutrophils and correlation with cellular functional parameters.

The effect of Salmonella enteritidis endotoxin on in vitro rat neutrophil cyclo-oxygenase and lipoxygenase metabolism, phagocytic activity, superoxide (O2-) generation, and microbicidal activity was investigated. Incubation of polymorphonuclear leukocytes (PMN) with 5, 25, and 50 micrograms of endotoxin significantly enhanced synthesis of immunoreactive (i) leukotriene (LT)C4/D4 and thromboxane (Tx)B2 (P less than 0.001) as compared to control cells. Endotoxin 5 micrograms/ml produced optimal stimulation of the arachidonic acid metabolites. Calcium ionophore, A23187, significantly enhanced iLTC4/D4 and iTxB2 synthesis more than that elicited with endotoxin. Although phagocytic function was not significantly altered by endotoxin, intracellular killing of C. albicans demonstrated enhanced microbicidal activity at 5 micrograms/ml of endotoxin. Superoxide generation was significantly enhanced in neutrophils stimulated with phorbol myristate acetate (PMA). Endotoxin (5 micrograms/ml) further potentiated superoxide generation by these cells when stimulated by PMA. These findings demonstrate that endotoxin directly enhances neutrophil iLTC4/D4 and iTxB2 synthesis. The enhanced arachidonic acid metabolism elicited by endotoxin in these cells parallels increased microbicidal activity and superoxide generation.

Animals↗
PubMed1988

Selective thromboxane synthetase inhibition by picotamide and effects on endotoxin-induced lethality.

The efficacy of N,N'-bis-(3-picolyl)-methoxyisophthalamide (picotamide) as an in vitro thromboxane synthetase inhibitor and its effect on endotoxin (LPS)-induced lethality in rats were assessed. Picotamide at 0.5 and 1.0 mM concentrations significantly (P less than 0.05) inhibited basal and LPS-stimulated synthesis of TxA2 measured by its stable immunoreactive (i) metabolite TxB2 in rat peritoneal macrophages. This compound did not inhibit synthesis of i6-keto-PGF1 alpha, the stable metabolite of PGI2, and produced significant shunting to i6-keto-PGF1 alpha. For lethality studies rats were pretreated, by gavage with picotamide, at either 75, 150, 300, or 600 mg/kg 2 hr prior to iv S. enteritidis (LPS, 20 mg/kg). Both 150 and 300 mg/kg doses of picotamide significantly (P less than 0.05) improved survival in endotoxin shock at 48 hr. These studies demonstrate that picotamide is a selective thromboxane synthetase inhibitor, and that it may be useful during disease states characterized by increased TxA2 synthesis.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Splanchnic artery occlusion shock in the rat: effects of the calcium entry blockers nimodipine and verapamil.

Splanchnic artery occlusion (SAO) shock made by clamping splanchnic arteries for 45 min was performed in female rats infused for 30 min with vehicle, nimodipine, and verapamil before, during, or after SAO. Survival time, macrophage phagocytosis and killing, and white cell count were evaluated in conscious rats. Shocked animals pretreated with vehicle exhibited 24.6 +/- 0.9% phagocytic activity, 5.1 +/- 0.7% killing activity, and survived 177 +/- 1.7 min. Leukopenia was also present. Sham animals survived more than 300 min, and showed the following values: phagocytosis = 52.8 +/- 0.6%, killing = 18.8 +/- 0.6%. Pretreatment with nimodipine (1 microgram/kg/min x 30 min, intravenously [IV]) before SAO significantly prolonged survival time (274 +/- 4.7 min) and improved phagocytosis (38.1 +/- 0.6%) and killing (16.1 +/- 1.1%), but did not change leukopenia. Lower doses of nimodipine (0.25 and 0.5 microgram/kg/min x 30 min, IV), and all the doses of verapamil (100 and 200 micrograms/kg/min x 30 min, IV), when infused before SAO, were ineffective. Neither nimodipine nor verapamil, when infused for 30 min either during or immediately after SAO, were able to influence survival, macrophage functions, or white cell count. Moreover, nimodipine (5, 10, and 25 microM), when added "in vitro" to macrophages collected from SAO-shocked rats, significantly enhanced their phagocytic activity, while verapamil (100 and 200 microM) did not change it. Finally, in anaesthetized rats nimodipine pretreatment had a beneficial effect on the cardiovascular changes occurring during SAO shock. These data suggest that nimodipine has a beneficial effect in SAO-shocked rats only when given before SAO.

Animals↗
PubMed1983

Cardiovascular responses of conscious rats to acute intravenous and intracerebroventricular administration of Shigella sonnei endotoxin.

Shigella sonnei lipopolysaccharide (LPS) was injected intravenous (iv) or into the lateral cerebral ventricle (icv) of freely moving rats. Iv injection of 320 micrograms/Kg reduced arterial blood pressure, increased heart rate and did not change pressor response and reflex bradycardia induced by iv bolus injection of phenylephrine (5 micrograms/Kg). Iv injection of 640 micrograms/Kg reduced arterial blood pressure and heart rate, and altered baroreceptor reflexes. Icv injection of LPS (up to 50 micrograms/rat) neither changed resting blood pressure and heart rate nor modified phenylephrine induced pressor response and reflex bradycardia. Results suggest that S. sonnei endotoxin determines cardiovascular changes mainly through baroreceptor resetting. Data also seem to rule out a central nervous system involvement.

Animals↗
PubMed1982

Cardiovascular effects of Shigella sonnei endotoxin in the rat.

Shigella sonnei lipopolysaccharide (LPS), either in phase I (extracted from the smooth strains), or in phase II (extracted from the rough strains) reduced mean arterial pressure and heart rate following a 640 micrograms/Kg intravenous (iv) bolus injection in the urethane-anesthetized rat. Lower doses were without significant effects. Escherichia coli LPS (640 micrograms/Kg iv) produced a greater and more prolonged hypotension, however the negative chronotropic effect was less severe. The iv injection of the lipid A moiety of the LPS molecule of Shigella sonnei resulted in a more pronounced hypotensive effect than that obtained with the parent LPS, thus showing that lipid A is the vasodilatating fraction of the molecule. When lipid A was injected in rats pretreated with aspirin or with naloxone, the hypotensive effect was significantly reduced and the decrease in heart rate was reverted in tachycardia. In atropine-pretreated, surgically bivagotomized rats, iv injection of lipid A was followed by a long-lasting pressor effect. The date indicate that Shigella sonnei endotoxin has cardiovascular effects, mainly due to its lipid A moiety of the molecule. The hypotensive effect involves a wide range of mechanisms.

Animals↗
PubMedDate not supplied

Splanchnic artery occlusion shock: vinblastine-induced leukopenia reduces tumour necrosis factor and thromboxane A2 formation, and increases survival rate.

This study was designed to assess the role of leukocytes in rats subjected to splanchnic artery occlusion for 45 min followed by reperfusion (SAO shock). Leukopenia was induced by an intravenous injection of vinblastine (1 mg/kg) 72 h before SAO shock. Survival rate (within 6 h), plasma levels of thromboxane B2 (TxB2), serum levels of tumour necrosis factor (TNF-alpha), and histological alteration of the intestinal tract were investigated. Control rats [white blood cells (WBC) = 10362 +/- 630/mm3] died within 2 h following ischaemia and reperfusion. Leukopenic (WBC = 1263 +/- 311/mm3) animals which underwent SAO shock survived more than 2 h and 50% of them were still alive after 6 h. Plasma TxB2 levels significantly increased in WBC count normal rats subjected to SAO shock (8.4 +/- 2.1 ng/ml), compared to sham animals (0.4 +/- 0.08 ng/ml); however SAO shock raised TxB2 levels significantly less (2.1 +/- 1.1 ng/ml) in leukopenic rats. Serum TNF-alpha, undetectable in sham-shocked rats (either with normal WBC count or without), rose up to 150 +/- 12 U/ml in shocked rate and to 45 +/- 5 U/ml (P < 0.01) in shocked animals with leukopenia. SAO shock induced a massive necrosis of the intestinal tract in rats with normal WBC count. Leukopenia prevented ileum necrosis in SAO shock. These data indicate that leukocytes play an important role in splanchnic artery occlusion and reperfusion.

Animals↗
PubMedDate not supplied

Different effects of bacterial lipopolysaccharide on superoxide anion production by macrophages from normal and tumor-bearing rats.

Bacterial endotoxins or lipopolysaccharides (LPS) exhibit a wide range of modulatory activities on immunocompetent cells. Among the numerous effects of LPS on macrophages, an enhancement of superoxide anion (O2-) release has been reported. In previous studies carried out on tumor-bearing rats, it was found that several functions of peritoneal macrophages such as phagocytic, microbicidal and antiviral activities were depressed. In this paper we evaluated the spontaneous or phorbol myristate acetate (PMA)-induced production of superoxide anion by macrophages from tumor-bearing rats with respect to controls. Moreover, the effect of in vitro priming with LPS on O2- production by the same cells was studied. It was found that the pattern of superoxide release by macrophages from tumor-bearing rats is significantly different from controls. Preincubation of macrophages from normal rats with LPS enhanced the spontaneous and PMA-induced production of O2-. In contrast, the same concentrations of LPS did not prime macrophages from tumor-bearing rats.

Animals↗
PubMedDate not supplied

Protective effects of BAY U 3405, a thromboxane A2 receptor antagonist, in endotoxin shock.

The present study was designed to investigate the effects of BAY U 3405, a new thromboxane A2 (TxA2) receptor antagonist, in endotoxin shock. Endotoxin shock (ES) was induced in male rats by an i.v. injection of Salmonella enteritidis lipopolysaccharide (LPS; 20 mg kg-1). LPS administration caused animal death (survival = 0%, 48 h after endotoxin challenge), systemic hypotension, depressed phagocytosis and increased blood levels of TNF-alpha, TxB2 and 6-keto-PGF1 alpha, reduced white blood cell (WBC) count (ES = 5.9 +/- 1 x 10(3) mm-3; CTRL = 13.4 +/- 5 x 10(3) mm-3) and enhanced myeloperoxidase (MPO) activity, studied as a quantitative means for assessing leukocyte accumulation, in the ileum (ES = 0.24 +/- 0.7 U g-1 fresh tissue; CTRL = 0.13 +/- 0.04 U g-1 fresh tissue), in the heart (ES = 0.41 +/- 0.1 U g-1 fresh tissue; CTRL = 0.16 +/- 0.08 U g-1 fresh tissue) and in the lung (ES = 0.68 +/- 0.11 U g-1 fresh tissue; CTRL = 0.19 +/- 0.05 U g-1 fresh tissue). Furthermore, endotoxin administration produced characteristic damage of the gastric mucosa consisting of haemmorrhagic infiltrates. BAY U 3405 (30 mg kg-1 i.v., 30 min before endotoxin challenge) increased survival rate (45% survival rate 48 h after endotoxin challenge), reduced hypotension, decreased TNF-alpha levels in serum, enhanced phagocytic activity (ES = 25.6 +/- 1.9%, BAY U 3405 = 45.9 +/- 0.4%, P < 0.001) and lowered MPO activity in the ileum (0.14 +/- 0.05 U g-1 fresh tissue), in the heart (0.18 +/- 0.08 U g-1 fresh tissue) and in the lung (0.44 +/- 0.09 U g-1 fresh tissue). Finally, the gastric alterations were significantly reduced in rats pretreated with BAY U 3405. These data suggest that this thromboxane receptor antagonist might be a useful drug in shock conditions.

Analysis of Variance↗