Leukocyte integrin very late antigen-4/vascular cell adhesion molecule-1 adhesion pathway in splanchnic artery occlusion shock.

We investigated the role played by the very late antigen-4 (VLA-4)/ vascular cell adhesion molecule-1 (VCAM-1) interaction in the pathogenesis of splanchnic artery occlusion shock. Splanchnic artery occlusion shock was induced in anaesthetized rats by clamping splanchnic arteries for 45 min. Sham operated animals were used as controls. Survival time, serum tumour necrosis factor (TNF-alpha), monocyte and lymphocyte cell count and the responsiveness to acetylcholine of aortic rings were studied. Furthermore we investigated the VCAM-1 expression on vessel endothelium and the percentage of VLA-4 positive leukocytes. Splanchnic artery occlusion shocked rats had a decreased survival time (76 +/- 10 min, while sham shocked rats survived more than 4 h), increased serum levels of TNF-alpha (328 +/- 11 U/ml), a decreased number of both monocytes and lymphocytes and reduced responsiveness to acetylcholine (10 nM-10 microM) of aortic rings. In addition we found an increased expression of endothelial VCAM-1 on aortic rings and a reduced percentage of VLA-4 positive lymphocytes and monocytes. Passive immunization with specific antibodies raised against either VCAM-1 or VLA-4 (2 mg/kg, i.v., 3 h before splanchnic artery occlusion shock) increased survival, improved monocyte and lymphocyte count and restored the responsiveness of aortic rings to acetylcholine (P < 0.01). Finally, inhibition of TNF-alpha biosynthesis reversed the increased endothelial expression of VCAM-1 and the reduced percentage of integrin VLA-4 positive leukocytes. Our findings suggest that (i) VLA-4/VCAM-1 interaction has a role in the pathogenesis of circulatory shock; (ii) this interaction might be a target for new therapeutic approaches to the therapy of low-flow states.

Monocytes and lymphocytes as active participants in the pathogenesis of experimental shock.

We investigated the role played by monocytes and lymphocytes in the pathogenesis of experimental shock. Splanchnic artery occlusion (SAO) shock was induced in anaesthetized rats by clamping splanchnic arteries for 45 min followed by reperfusion. Sham operated animals were used as controls. SAO shocked rats had a decreased survival time (80 +/- 11 min, while sham shocked rats survived more than 4 h), increased serum (248 +/- 21 U/ml) and macrophage (145 +/- 15 U/ml) levels of TNF-alpha, enhanced myeloperoxidase (MPO) activity in the ileum (3.38 +/- 0.2 U x 10(-3)/g tissue), decreased number of monocytes, lymphocytes and neutrophils and a profound hypotension. In addition we found an increased expression of vascular cell adhesion molecule-1 (VCAM-1) on aortic endothelium and a reduced percentage of VLA-4 positive monocytes and lymphocytes. Inhibition of TNF-alpha synthesis, reversed the increased endothelial expression of VCAM-1, increased the percentage of integrin VLA-4 positive leukocytes and improved monocyte, lymphocyte and neutrophil count. Furthermore a passive immunization with specific antibodies raised against VCAM-1 (2 mg/kg, i.v. 3 h before SAO) increased survival, reduced MPO activity in the ileum (0.034 +/- 0.04 U x 10(-3)/g tissue) and improved mean arterial blood pressure. Our data suggest that monocytes and lymphocytes participate in the pathogenesis of splanchnic ischaemia-reperfusion injury and may amplify the adhesion of neutrophils to peripheral tissues.

Improved survival and reversal of endothelial dysfunction by the 21-aminosteroid, U-74389G in splanchnic ischaemia-reperfusion injury in the rat.

1. Anaesthetized rats subjected to total occlusion of the superior mesenteric artery and the coeliac trunk for 45 min developed a severe shock state (splanchnic artery occlusion, SAO shock) resulting in death within 70-90 min after release of the occlusion. Sham-operated animals were used as controls. 2. Survival rate, survival time, serum tumour necrosis factor (TNF-alpha), white blood cell (WBC) count, mean arterial blood pressure (MAP), plasma malonyladehyde (MAL); myeloperoxidase activity (MPO) and the responsiveness to acetylcholine (ACh 10 nM-10 microM) of aortic rings were investigated. 3. SAO shocked rats had a decreased survival rate and survival time (74 +/- 10 min, while sham-shocked rats survived more than 4 h), reduced mean arterial blood pressure, increased serum levels of TNF-alpha (267 +/- 13 u ml-1) and plasma levels of MAL (57 +/- 7 nmol ml-1), enhanced MPO activity in the ileum (0.23 +/- 0.04 u x 10(-3) g-1 tissue) and in the lung (2.2 +/- 0.8 u x 10(-3) g-1 tissue), leukopenia and reduced responsiveness to ACh of aortic rings. 4. The 21-aminosteroid U-74389G (30 mg kg-1, i.v.) increased survival (survival time = 232 +/- 15 min), lowered the serum levels of TNF-alpha and the plasma levels of MAL, reduced leukopenia and MPO activity both in the ileum (0.021 +/- 0.004 u x 10(-3) g-1 tissue) and in the lung (0.23 +/- 0.03 u x 10(-3) g-1 tissue), improved MAP and restored the responsiveness to ACh of aortic rings. 5. Our data suggest that U-74389G is a potent lipid peroxidation inhibitor and that it has antishock and endothelial protective actions.

E-selectin involvement in the pathogenesis of splanchnic artery occlusion shock.

We investigated the involvement of E-selectin in the pathogenesis of splanchnic artery occlusion shock. Splanchnic artery occlusion shock was induced in anaesthetized rats by clamping splanchnic arteries for 45 min. Sham-operated animals were used as controls. Survival time, serum tumor necrosis factor-alpha, while blood cell count, mean arterial blood pressure and myeloperoxidase activity were determined. Splanchnic artery occlusion-shocked rats had a decreased survival time (85 +/- 8 min, while sham-shocked rats survived more than 4 h), reduced mean arterial blood pressure, increased serum levels of tumor necrosis factor-alpha (186 +/- 9 U/ml) and myeloperoxidase activity in the ileum (0.10 +/- 0.04 U x 10(-3)/g tissue) and in the lung (1.5 +/- 0.06 U x 10(-3)/g tissue). Shocked rats showed histological alterations in the ileum and in the lung. Administration of a hyperimmune serum containing specific antibodies raised against E-selectin significantly increased survival time (225 +/- 10 min), reduced leukopenia and myeloperoxidase activity both in the ileum (0.035 +/- 0.001 U x 10(-3)/g tissue) and in the lung (0.3 +/- 0.005 U x 10(-3)/g tissue), improved the cardiovascular changes and reduced the histological alterations in the ileum and lung. Our data are consistent with an involvement of E-selectin in the pathogenesis of splanchnic artery occlusion shock.

Participation of tumour necrosis factor and nitric oxide in the mediation of vascular dysfunction in splanchnic artery occlusion shock.

1. Splanchnic artery occlusion (SAO) shock is characterized by irreversible circulatory failure. Tumour necrosis factor (TNF-alpha) may affect the L-arginine/nitric oxide (NO) pathway, thus contributing to the cardiovascular derangements of circulatory shock. 2. We investigated the contribution of both TNF-alpha and the L-arginine/nitric oxide pathway to the vascular dysfunction of SAO shock. Anaesthetized rats, subjected to total occlusion of the superior mesenteric artery and the coeliac trunk for 45 min developed a severe shock state (SAO shock) resulting in a fatal outcome within 75-90 min after the release of occlusion. Sham operated animals were used as controls. SAO shocked rats had also a marked hypotension and enhanced macrophage and serum levels of TNF-alpha. Furthermore, aortic rings from shocked rats showed a marked hyporeactivity to phenylephrine (PE 1 nM-10 microM) and reduced responsiveness to acetylcholine (ACh 10 nM-10 microM). Endothelium-denuded aortic rings had also a marked hyporeactivity to phenylephrine, which was restored to control values by in vitro administration of NG nitro-L-arginine-methyl ester (L-NAME 10 microM). 3. In vivo administration of cloricromene (2 mg kg-1, i.v.), an inhibitor of TNF-alpha biosynthesis, increased survival, enhanced mean arterial blood pressure and reduced macrophage and serum levels of TNF-alpha. Furthermore, aortic rings from shocked rats treated with cloricromene exhibited a greater contractile response to phenylephrine and improved responsiveness to ACh when compared to aortic rings from vehicle-treated SAO shocked rats. 4. Our results suggest that TNF-alpha alters both endothelial and muscular L-arginine/nitric oxide pathways which in turn produce vascular dysfunction in SAO shock.

Contribution of intercellular adhesion molecule 1 (ICAM-1) to the pathogenesis of splanchnic artery occlusion shock in the rat.

1. It has been suggested that leukocytes play a key role in the pathogenesis of splanchnic artery occlusion shock. Intercellular adhesion molecule 1 (ICAM-1) is an adhesion molecule of crucial importance in the phenomenon of leukocyte accumulation. 2. We investigated the involvement of ICAM-1 in the pathogenesis of splanchnic artery occlusion shock. Splanchnic artery occlusion (SAO) shock was induced in anaesthetized rats by clamping splanchnic arteries for 45 min. Sham-operated animals were used as controls. Survival time, serum tumour necrosis factor-alpha (TNF-alpha), white blood cell (WBC) count, mean arterial blood pressure, myeloperoxidase activity (MPO; studied as a quantitative means to assess leukocyte accumulation) and the responsiveness to acetylcholine of aortic rings were investigated. SAO shocked rats had a decreased survival time (90 +/- 9.5 min, while sham-shocked rats survived more than 4 h), reduced mean arterial blood pressure, increased serum levels of TNF-alpha (201 +/- 10 mu ml-1) and MPO activity in the ileum (0.15 +/- 0.03 mu x 10(-3) per g tissue) and in the lung (1.9 +/- 0.8 mu x 10(-3) per g tissue), leukopenia and reduced responsiveness to acetylcholine (ACh, 10 nM-10 microM) of aortic rings. 3. Administration of monoclonal antibody raised against rat ICAM-1 significantly increased survival time (225 +/- 9 min), reduced leukopenia and MPO activity both in the ileum (0.031 +/- 0.003 mu x 10(-3) per g tissue) and in the lung 0.23 +/- 0.03 mu x 10(-3) per g tissue), improved the cardiovascular changes and restored the responsiveness to ACh of aortic rings. 4. Our findings are consistent with an involvement of adhesion mechanisms in vivo in the pathogenesis of SAO shock and suggest that specific adhesion mechanisms, which support leukocyte accumulation,may represent potentially important therapeutic targets in circulatory shock.

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.

[Epidemiologic surveillance of influenza in Rome 1982-1984]. / Sorveglianza epidemiologica dell'influenza in Roma nel periodo 1982-1984.

In the periods from July 1982 to June 1983 and July 1983 to June 1984, 31 strains of influenza virus, of which 19 A/H3N2 6 A/H1N1 and 6 type B, were isolated from 242 throat cultures obtained from patients with acute febrile respiratory disease. A seroepidemiological survey on 520 serum samples confirms significant activity of influenza viruses during the winterly period of 1983-1984. In the period July-August 1983 the evaluation of mortality from respiratory diseases presents an excess in respect of epidemic threshold probably ascribable to heat stroke.

Comparison of complement fixation, immunofluorescence and immunoenzymatic tests for routine detection of cytomegalovirus IgG antibodies.

Complement fixation (CF), immunofluorescence (IF) and immunoenzymatic (ELISA) tests by commercial sources were compared, for routine laboratory detection of cytomegalovirus IgG antibodies, on 120 serum samples from normal pregnant females. IF and ELISA were comparable in terms of specificity and sensitivity, but in our opinion ELISA showed some advantages with regard to need for facilities and trained personnel. CF could not detect some of low titer positive sera, so it can not be suggested where it is critical to know a previous contact with the virus, as in blood donors or transplant donors and recipients.

[Epidemiologic surveillance of influenza in Rome (1981-1982)]. / Sorveglianza epidemiologica dell'influenza in Roma (1981-1982).

In the period from September 1981 to April 1982, one strain of influenza virus (A-H3N2) was isolated from 121 throat cultures obtained from patients with acute febrile respiratory disease. A sero-epidemiological survey on 520 serum samples and evaluation of excess mortality from respiratory diseases did not show significant activity of influenza viruses during the period from October 1981 to October 1982.