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Biomedical subjects

G Calapai

Publications and source records attributed to G Calapai.

49 records · Page 3Linked to original sources
PubMed1993

The effect of cloricromene, a coumarine derivative, on leukocyte accumulation, myocardial necrosis and TNF-alpha production in myocardial ischaemia-reperfusion injury.

The effects of cloricromene, a coumarine derivative, were studied in an anaesthetized rat model of coronary artery ligation (60 min) followed by reperfusion (60 min; MI/R). Sham operated rats were used as controls (Sham MI/R). Myocardial ischaemia-reperfusion injury produced a marked myocardial injury (necrotic area/area-at-risk = 68 +/- 4%; necrotic area/total area = 48 +/- 3%) high serum creatinphosphokinase activity (Sham MI/R = 29 +/- 8 U/ml; MI/R = 205 +/- 11 U/ml) and elevated myocardial myeloperoxidase activity (investigated as an index of leukocyte adhesion and accumulation), in the area-at-risk (6.3 +/- 0.2 U x 10(-3)/g tissue) and in necrotic area (6.5 +/- 0.5 U x 10(-3)/g tissue). Furthermore, serum TNF-alpha was undetectable during the occlusion period, but upon the release of the coronary artery significantly increased. At the end of reperfusion, macrophage TNF-alpha was also enhanced. The administration of cloricromene (2 mg/kg, 5 minutes after the onset of reperfusion) significantly reduced myocardial injury (necrotic area/area-at-risk 30 +/- 1.3%; necrotic area/total area = 25 +/- 1.5) blunted the increase in serum creatinphosphokinase activity (92 +/- 5 U/ml) and lowered myeloperoxidase activity in area-at-risk (2.5 +/- 0.2 U x 10(-3)/g tissue) and in necrotic area (2.2 +/- 0.3 U x 10(-3)/g tissue) and decreased the serum and macrophage levels of TNF-alpha. These data indicate that cloricromene exerts beneficial effects on myocardial ischaemia/reperfusion injury. Finally, since we measured increased serum levels of TNF-alpha that were blunted by the cloricromene treatment, our data are consistent with an involvement of TNF-alpha in the reperfusion injury induced by myocardial ischaemia.

Analysis of Variance↗
PubMed1993

A new antioxidant drug limits brain damage induced by transient cerebral ischaemia.

Restoration of blood flow after an ischaemic event generates the formation of oxygen radicals which could augment brain damage. The authors studied the effects of different doses (50, 100, 200 mg/kg/i.p.) of a new antioxidant, IRFI-016, [2(2,3-dihydro-5-acetoxy-4,6,7-trimethylbenzofuranyl) acetic acid] on brain damage in the Mongolian gerbil induced by 5 min of bilateral carotid occlusion (BCO) followed by reperfusion. Post-ischaemic brain malondialdehyde (MDA) levels and locomotor activity at different times and delayed neuronal death of hippocampal CA1 area on the fourth day after occlusion were evaluated. During reperfusion, after BCO, enhancement of brain MDA occurs (37.5%, 62.5% and 100% at 15, 30 and 60 min of reperfusion, respectively). Brain MDA postischaemic increases were reduced at 15 min of reperfusion to 15.4% and 44.4% by IRFI-016, 100 and 200 mg/kg, respectively. After 30 min of reperfusion brain MDA was reduced to 31.25% and 53.13% by IRFI-016 100 and 200 mg/kg, respectively. Hyperactivity and delayed neuronal death of CA1 were significantly reduced in postischaemic gerbils treated with the highest doses of IRFI-016. Results indicate that pretreatment with the antioxidant IRFI-016 improves in a dose-dependent manner brain damage induced by ischaemia and reperfusion in the gerbil.

Animals↗
PubMed1993

Platelet activating factor interaction with tumor necrosis factor in myocardial ischaemia-reperfusion injury.

The role played by platelet-activating factor (PAF) and tumor necrosis factor (TNF-alpha) in myocardial ischaemia-reperfusion injury was investigated. Pentobarbital anaesthetized rats were subjected to left main coronary artery ligation (1 h) followed by reperfusion (1 h; MI/R). Sham-operated rats were used as controls (Sham MI/R). Myocardial ischaemia-reperfusion injury produced a marked myocardial injury (necrotic area/area-at-risk = 60 +/- 5%; necrotic area/total area = 50 +/- 6%), high serum creatine phosphokinase activity (Sham MI/R = 25 +/- 10 U/ml; MI/R = 190 +/- 12 U/ml), a severe leukopenia (Sham MI/R = 10367 +/- 630 WBC x mm3; MI/R = 4123 +/- 120 WBC x mm3) and elevated myocardial myeloperoxidase activity (investigated as an index of leukocytes adhesion and accumulation) in the area-at-risk (6.2 +/- 0.5 U x 10(-3)/g tissue) and in necrotic area (6.6 +/- 0.7 U x 10(-3)/g tissue. Plasma PAF and serum TNF-alpha were significantly increased only during reperfusion. The peak of PAF plasma levels (6.5 +/- 1.2 pmol/ml) occurred earlier (15 min of reperfusion) than the peak of serum TNF-alpha (150 U/ml at 30 min of reperfusion). At the end of reperfusion, macrophage TNF-alpha was also enhanced (Sham MI/R = undetectable; MI/R = 148 +/- 12 U/ml). The administration of CV 6209, a specific PAF receptor antagonist (5 mg/kg, 5 min after occlusion), significantly reduced myocardial injury (necrotic area/area-at-risk = 27 +/- 3%, P < 0.001; necrotic area/total area = 10 +/- 2%, P < 0.001), blunted the increase in serum creatine phosphokinase (70 +/- 12 U/ml), partially restored leukopenia (8234 +/- 143 WBC x mm3) and lowered myeloperoxidase activity in area-at-risk (2.3 +/- 0.3 U x 10(-3)/g tissue; P < 0.001) and in necrotic area (2.8 +/- 0.5 U x 10(-3)/g tissue). In addition, administration of CV 6209 reduced the serum and macrophage levels of TNF-alpha. The results of this study, therefore, suggest that PAF and TNF-alpha are key mediators of myocardial ischaemia-reperfusion injury and that PAF plays a permissive role in inducing the release of other factor(s) relevant to reperfusion injury.

Analysis of Variance↗
PubMed1992

Cloricromene, a coumarine derivative, protects against lethal endotoxin shock in rats.

Endotoxin shock was induced in male rats by an intravenous (i.v.) injection of Salmonella enteriditis lipopolysaccharide (LPS; 20 mg/kg i.v.). Survival rate, macrophage and serum tumor necrosis factor (TNF-alpha), mean arterial blood pressure (MAP) and white blood cell count were then evaluated. Furthermore the in vitro effect of cloricromene on peritoneal macrophage phagocytosis and TNF-alpha release by primed peritoneal macrophages was investigated. LPS administration caused animal death (0% survival 24 h after endotoxin challenge), hypotension, marked leukopenia and increased the levels of TNF-alpha in both serum and macrophage supernatants. Cloricromene administration (0.5, 1 and 2 mg/kg i.v. 15 min after endotoxin) protected against LPS-induced lethality (100% survival rate 24 h after endotoxin challenge), reverted LPS-induced hypotension and leukopenia, and decreased TNF-alpha in both serum and macrophage supernatants. Finally, cloricromene, added in vitro to peritoneal macrophages collected from endotoxin-treated rats increased macrophage phagocytosis and reduced TNF-alpha formation by activated mononuclear phagocytes. Our data suggest that cloricromene increases survival rate in endotoxin shock through an inhibition of TNF-alpha production.

Animals↗
PubMed1992

Cloricromene antagonizes antidipsogenic effects induced by endotoxin, but not by TNF alpha, in the rat.

Intravenous (640 micrograms/kg) or intracerebroventricular (0.5 and 1 microgram) injection of Escherichia coli endotoxin (LPS) causes inhibition of water intake induced by 24 hour period of water deprivation in the rat. Tumor necrosis factor alpha (TNF-alpha; 20 and 40 ng/rat) given into the lateral cerebral ventricle (i.c.v.) causes effects similar to those observed after LPS. Cloricromene, given either intravenously (1 and 2 mg/kg) or i.c.v. (250 and 500 ng), abolished the antidipsogenic effect induced by LPS (administered both i.v. and i.c.v.). Cloricromene (2 mg/kg, i.v. or 500 ng/rat, i.c.v.), on the contrary, did not modify the antidipsogenic effects induced by TNF-alpha. These data indicate that peripherally injected cloricromene (as well as that i.c.v. injected) antagonizes the effects of mediators of LPS on sites regulating thirst and suggest that cloricromene's action may be due to inhibition of brain TNF-alpha formation induced by LPS.

Animals↗
PubMed1992

Evidence that nitric oxide modulates drinking behaviour.

The involvement of the L-arginine-nitric oxide (NO) pathway in brain, in the regulation of drinking behaviour, has been evaluated by injecting L-arginine and N omega-nitro-L-arginine methyl ester (L-NAME) into the lateral cerebral ventricle (i.c.v.). L-Arginine (5 and 10 micrograms/rat), but not D-arginine, was antidipsogenic when administered to 24 hr water-deprived rats but did not change the intake of water in normally hydrated rats. However, L-NAME (5 and 10 micrograms/rat) did antagonize the effect of L-arginine in water-deprived animals but, by itself, did not increase thirst. L-Arginine (100 ng), when injected into the preoptic area significantly reduced water deprivation-induced drinking. The same dose was unaffective when given intraventricularly. Finally, L-arginine (5 and 10 micrograms/rat, i.c.v.) inhibited drinking induced by intraventricular injection of angiotensin II (250 ng/rat). The effect was dose-dependent. The results indicate that: (1) NO acts as an inhibitory mechanism when thirst is stimulated by water deprivation or by angiotensin II; (2) the preoptic area might be one of the central sites of antidipsogenic action of NO and (3) nitric oxide synthase might be inhibited during water deprivation.

Angiotensin II↗
PubMed1992

Protective effects of G 619, a dual thromboxane synthase inhibitor and thromboxane A2 receptor antagonist, in splanchnic artery occlusion shock.

Splanchnic artery occlusion (SAO) shock was induced in anesthetized rats by clamping the celiac trunk and the superior mesenteric artery for 45 min. The arteries were then released and survival rate, mean survival time, mean arterial blood pressure (MAP), plasma levels of thromboxane B2 (TxB2) and 6-keto-PGF1 alpha, and the phagocytotic activity of peritoneal macrophages were evaluated. Shocked animals died within 89 +/- 10 min, while all sham-shocked rats survived greater than 3 h. SAO shock produced relevant changes in MAP, significantly increased plasma levels of TxB2 and 6-keto-PFG1 alpha, and decreased peritoneal macrophage phagocytotic activity. The administration of G 619, a dual thromboxane synthase inhibitor/thromboxane A2 receptor antagonist (50 mg/kg, 15 min before SAO shock) significantly increased survival time (190 +/- 13 min) and survival rate, reduced plasma levels of TxB2, and partially restored the impairment in peritoneal macrophage phagocytosis. Finally, the administration of G 619 had beneficial effects on changes in MAP-induced bay SAO shock. These data further confirm the involvement of TxA2 in SAO shock and suggest that G 619 may have positive effects in low-flow states.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Evidence for a role of nitric oxide in hypovolemic hemorrhagic shock.

Hypovolemic hemorrhagic shock was induced in rats by intermittently withdrawing blood from an iliac catheter for 20 min until mean arterial blood pressure (MAP) decreased to 30 mm Hg. Survival rate, survival time, plasma myocardial depressant factor (MDF) activity, MAP, and microscopic gastric alterations were then evaluated. NG-nitro-L-arginine methyl-ester (L-NAME), a selective inhibitor of nitric oxide (NO) production from L-arginine, was injected intravenously (i.v.) after the bleeding was discontinued. Untreated hemorrhagic shocked rats died in 27 +/- 3.3 min, had enhanced plasma activity of MDF, and exhibited hemorrhagic infiltrates in gastric fundus mucosa. L-NAME (5 and 10 mg/kg) significantly increased survival rate and time, blunted the increase in plasma MDF activity, and protected against the gastric lesions induced by hemorrhagic hypovolemic shock. All these protective effects were reversed by a bolus of L-arginine (30 mg/kg/i.v.), given 2 min after administration of L-NAME. Our findings suggest that NO production plays an important role in the pathophysiology of hemorrhagic shock.

Animals↗
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↗
PubMed1987

Central dipsogenic effect of synthetic rat atrial natriuretic polypeptide in normotensive rats.

The effect of intracerebroventricular (i.c.v.) injection of synthetic rat atrial natriuretic polypeptide (alpha-rANP) on drinking behavior was studied in normotensive rats, alpha-rANP (0.2, 0.4 or 0.8 micrograms in 5 microliter) caused a dose-dependent dipsogenic effect which was abated by i.c.v. pretreatment with saralasine (9 micrograms in 5 microliter). These results suggest that alpha-rANP possesses dipsogenic effects in water repleted rats and that brain angiotensin is involved. In addition, our data indicate that, at least as far as the effect of cerebral ANP is concerned, there are some differences between alpha-rANP and human atrial natriuretic polypeptide.

Animals↗
PubMedDate not supplied

Endotoxin inhibition of drinking behaviour in the rat.

Intravenous (i.v. 320 and 640 micrograms/kg) and intracerebroventricular (i.c.v.; 1 microgram/rat) injection of Escherichia coli lipopolysaccharide (LPS) powerfully inhibited drinking induced by 24 h water deprivation. Pretreatment with acetylsalicylic acid (ASA) into the preoptic area (POA) completely abolished the effect induced by i.v. LPS, but did not modify that elicited by i.c.v. LPS. Intraperitoneal ASA injections significantly reduced the antidipsogenic effect of i.c.v. LPS. Electrolytic ablation of the subfornical organ (SFO) did not modify the effect induced by either i.v. or i.c.v. LPS. Present findings indicate that: (1) the antidipsogenic effect of i.v. LPS is mediated by prostaglandin synthesis into the POA, (2) the SFO is not involved in this effect, and (3) prostaglandins in other brain areas, besides POA, modulate the effect of i.c.v. LPS. It is suggested that at least two different brain sites, inside the blood-brain barrier, might be involved in the antidipsogenic effect of LPS.

Animals↗