Biomedical subjects

G Calapai

Publications and source records attributed to G Calapai.

At least 37 records · Page 2Linked to original sources

PubMed1997

Interleukin-1 inhibits drinking behaviour through prostaglandins, but not by nitric oxide formation.

Interleukin-1 beta (IL-1 beta) causes inhibition of drinking behaviour. Moreover it induces formation of prostaglandins (PGs) and nitric oxide (NO). Both PGs and NO are able to inhibit drinking stimulated by water deprivation or by intracerebroventricular (i.c.v.) administration of angiotensin II. In this study, we studied in the preoptic area (POA) the possible role of PGs and NO in the antidipsogenic action induced by IL-1 beta. IL-1 beta was injected in the lateral cerebral ventricle (i.c.v.) (2.5, 10, 20, and 40 ng/rat) or into POA (0.625, 1.25, 2.5, and 10 ng/rat). L-arginine (12.5, 25, 50, and 100 ng/rat), the precursor of NO, or NG-nitro-L-arginine methyl ester (L-NAME) (25, 50, and 100 ng/rat), an inhibitor of nitric oxide synthase (NOS), were injected only into POA. Drinking behaviour was induced by water deprivation (24 h). IL-1 beta injected either i.c.v. or into POA caused dose dependent inhibition of drinking. In the POA a treatment with acetylsalicylic acid (ASA) (33, 66, and 135 micrograms/rat), but not with L-NAME, antagonized the inhibition of drinking behaviour induced by the highest doses of IL-1 beta in the POA. In the POA, a treatment with ASA or L-NAME antagonized the inhibition of drinking behaviour caused by injection of the highest doses of L-arginine. Our data suggest that the central inhibition of drinking behaviour of IL-1 beta is mediated through the formation of PGs, but not NO, in the POA.

Animals↗

PubMed1997

Effects of interleukin-10 on water intake, locomotory activity, and rectal temperature in rat treated with endotoxin.

Intracerebroventricular (i.c.v.) interleukin-10 (25, 50, and 100 ng/rat) effects on water intake, exploratory behaviour, and rectal temperature were evaluated in rats treated intraperitoneally (i.p.) with lipopolysaccharide (0.32, 0.64, and 0.96 mg/kg). Endotoxin administration induced fever and inhibition of thirst in water-deprived rats, and a decrease in lococomotory activity in normohydrated and water-deprived animals. Our data show that interleukin-10 during lipopolysaccharide administration controlled fever, increases exploratory behaviour, but did not reverse lipopolysaccharide inhibition of thirst. These effects suggest that fever, depression in locomotory activity but not inhibition of thirst, induced by endotoxin are influenced by interleukin-10 levels.

Animals↗

PubMed1997

Multiple organ failure following zymosan-induced peritonitis is mediated by nitric oxide.

In the present study we tested the hypothesis that nitric oxide may play a role in the pathogenesis of multiple organ failure induced by peritoneal injection of zymosan in the rat. A severe inflammatory response characterized by peritoneal exudation, high plasma and peritoneal levels of nitrate/ nitrite (breakdown products of nitric oxide), prostaglandin E2 and leukocyte infiltration into peritoneal exudate was induced by zymosan administration. This inflammatory process started within 3 h of administration and onset occurred at 18 h, coinciding with damage of lung, small intestine and liver, as assessed by histological examination and by increase of myeloperoxidase activity, indicative of neutrophil infiltration. Furthermore, at 18 h after zymosan-induced peritonitis, expression of inducible nitric oxide synthase enzyme was found mainly in the macrophages of inflamed lungs. Subcutaneously administration of a nonisoform selective nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester, reduced formation of peritoneal exudate fluid, blocked plasma and peritoneal nitrate/nitrite accumulation, and attenuated the elevated release of peritoneal prostaglandin E2. In addition, nitric oxide synthase inhibition was effective in preventing the development of organ failure since tissue injury and neutrophil infiltration, by myeloperoxidase evaluation, was reduced in lung, small intestine, and liver. In conclusion, major findings of our study are that nitric oxide exerts a proinflammatory role in the development of multiple organ failure and nitric oxide synthase inhibition is an effective antiinflammatory therapeutic tool, since inhibits not only nitric oxide but also prostaglandin production and cellular infiltration in inflamed organs.

Acute Disease↗

PubMed1997

Effects of some excitatory amino acid antagonists and drugs enhancing gamma-aminobutyric acid neurotransmission on pefloxacin-induced seizures in DBA/2 mice.

The behavioral and convulsant effects of pefloxacin (PEFLO), a quinolone derivative, were studied after intraperitoneal (i.p.) administration to Dilute Brown Agouti DBA/2J (DBA/2) mice, a strain genetically susceptible to sound-induced seizures. The anticonvulsant effects of some excitatory amino acid (EAA) antagonists acting at N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) receptors and of some compounds enhancing gamma-aminobutyric acid (GABA)-ergic transmission against seizures induced by PEFLO were also evaluated. The present study demonstrated that both groups of compounds administered i.p. or intracerebroventricularly were able to protect against seizures induced by PEFLO. However, ifenprodil and (+/-)-alpha-(chlorophenyl)-4-[(4-fluorophenyl)methyl]-1-piperidine-ethan ol (SL 82.0715), two compounds acting on the polyamine site of the NMDA receptor complex, were unable to provide any protection. The relationship between the different sites of action and the anticonvulsant activities of these derivatives were discussed. Although the main mechanisms of PEFLO-induced seizures cannot be easily determined, potential interactions with the receptors of EAA exist. In fact, antagonists of EAA, and in particular, those acting at NMDA receptors, were able to increase the threshold for the seizures or to prevent the seizures induced by PEFLO, while compounds acting at the polyamine site did not provide any protection. The AMPA-KA receptor antagonists were also able to exert anticonvulsant activity, but with minor potency in comparison to those of NMDA antagonists. In addition, the fact that compounds enhancing GABA-ergic neurotransmission were also able to protect the mice against seizures induced by PEFLO suggests an involvement of GABA system.

4-Quinolones↗

PubMed1996

Nitric oxide and drinking behaviour.

The role of brain L-arginine/nitric oxide biochemical pathway in the regulation of drinking behaviour was investigated. Drinking was induced by water deprivation or by intracerebroventricularly (i.c.v.) injected angiotensin II. L-Arginine, the amino-acid precursor of nitric oxide, i.c.v. injected, caused a dose-dependent reduction of the intake of water induced both by water deprivation and i.c.v. angiotensin II (P < 0.001). L-NAME, inhibitor of nitric oxide synthase, reverted L-arginine antidipsogenic effect. L-Arginine, given into the preoptic area (POA) caused a potent antidipsogenic effect (P < 0.001). Either methylene blue (inhibitor of guanylate cyclase activation) or acetylsalicylic acid (ASA), injected into the POA, antagonized the antidipsogenic effect of i.c.v. injected L-arginine. The results indicate that nitric oxide acts as an inhibitory mechanism into the POA and that its antidipsogenic effect requires prostaglandin synthesis.

Angiotensin II↗

PubMed1996

Interleukin-1 receptor antagonist does not reverse lipopolysaccharide-induced inhibition of water intake in rat.

The involvement of interleukin-1 in antidipsogenic effects induced by intraperitoneal (i.p.) administration of lipopolysaccharide (0.32, 0.64 and 0.96 mg/kg) in 24-h water-deprived rats, was evaluated by injection of human interleukin-1 receptor antagonist (10, 25 and 50 micrograms/rat) into the lateral cerebral ventricle (i.c.v.). The effects of either lipopolysacharide or human interleukin-1 receptor antagonist treatment on rectal temperature of 24-h water-deprived rats, were examined. Our date show that human interleukin-1 receptor antagonist administration is able to reverse, dose dependently, fever, but not lipopolysaccharide inhibition of thirst. The reduction of pyrogenic, but not of antidipsogenic, effects of lipopolysaccharide following human interleukin-1 receptor antagonist administration suggests that lipopolysaccharide inhibition of thirst is not dependent on interleukin-1 induced fever and that interleukin-1 is not a direct mediator implicated in inhibition of water intake provoked by peripheral injection of lipopolysaccharide.

Animals↗

PubMed1996

Inhibition of nitric oxide formation reduces voluntary ethanol consumption in the rat.

Brain nitric oxide is involved in the mechanisms that regulate ingestive behavior. To test whether this compound plays a role in alcohol preference, we studied the effects of different doses of NG-nitro-L-arginine (L-NO arg), an inhibitor of nitric oxide synthase (NOS), on voluntary consumption of ethanol and on blood alcohol levels produced by a single intraperitoneal dose of alcohol in the rat. L-NO arg produced a significant and dose-dependent reduction of ethanol intake (P < 0.001) without influencing total fluid consumption or feeding behavior. L-NO arg did not influence the kinetics of alcohol. Our data show that inhibition of nitric oxide formation accompanies reduction of ethanol intake and suggest a possible role for nitric oxide in ethanol self-administration.

Alcohol Drinking↗

PubMed1995

Multiple actions of the coumarine derivative cloricromene and its protective effects on ischemic brain injury.

The effects of different doses (0.25, 0.5, 1 and 2 mg/kg i.p.) of cloricromene, a coumarine derivative, have been investigated on brain malondialdehyde levels, brain edema, myeloperoxidase activity, survival, locomotor hyperactivity and hippocampal neuronal loss following transient cerebral ischemia induced by temporary bilateral carotid occlusion in the Mongolian gerbil. Cloricromene reduced brain lipid peroxidation, measured through the evaluation of malondialdehyde (-82.9% with the highest dose), and the formation of post-ischemic brain edema, evaluated by water content. The increase in myeloperoxidase activity observed in the hippocampus of postischemic animals was also reduced: 0.7 +/- 0.3 U x 10(-3) vs. 3.3 +/- 0.3 U x 10(-3)/g tissue. The same treatment increased survival and reduced hyperactivity linked to neurodegeneration induced by cerebral ischemia and reperfusion. Histological observations of the pyramidal layer of CA1 showed a reduction of neuronal loss in animals that received the drug before occlusion but not in those that were treated after the occlusion. These results show that cloricromene, a drug with multiple actions, improves brain injury induced by transient cerebral ischemia.

Animals↗

PubMed1994

Central serotoninergic system involvement in the anorexia induced by NG-nitro-L-arginine, an inhibitor of nitric oxide synthase.

The effects of NG-nitro-L-arginine, an inhibitor of brain nitric oxide (NO) synthase, on central serotoninergic system were studied in male obese Zucker rats and in their lean age-matched controls (FA/?; FA/FA), both groups aged 14 weeks. Acute injection of NG-nitro-L-arginine (50 mg/kg i.p.) or repeated administration of NG-nitro-L-arginine (50 mg/kg i.p. daily, for 7 days) reduced food intake and body weight in obese rats. Acute administration of NG-nitro-L-arginine reduced food intake in lean rats. However, lean rats showed tolerance to the NG-nitro-L-arginine effects after repeated administration. NG-Nitro-L-arginine administration significantly increased serotonin metabolism in the cortex, diencephalon and medulla-pons of obese Zucker rats after either acute or repeated administration of NG-nitro-L-arginine. In contrast, NG-nitro-L-arginine increased serotonin metabolism in lean rats only after acute administration, and the appearance of tolerance to NG-nitro-L-arginine anorectic effects paralleled the failure of NG-nitro-L-arginine to increase serotonin metabolism. The present data extend our previous findings indicating that NG-nitro-L-arginine possesses anorectic activity in obese Zucker rats, and clearly suggest that the central serotoninergic system mediates the anorexia induced by inhibitors of brain NO synthase.

Amino Acid Oxidoreductases↗

PubMed1994

Food deprivation increases brain nitric oxide synthase and depresses brain serotonin levels in rats.

We studied nitric oxide (NO) synthase activity and serotonin content in the diencephalon of 24 hr food deprived rats. NO synthase activity was significantly increased whereas serotonin levels together with those of tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) were reduced in food deprived rats when compared to control rats. NG-Nitro-L-arginine (L-NO Arg), an inhibitor of NO synthase, was used as a tool to study the role of NO in food deprivation. Twenty-four hr food deprived male Sprague-Dawley rats were intraperitoneally (i.p.) administered L-NO Arg (12.5, 25 and 50 mg/kg) before food presentation. Control rats received a NaCl (0.9%) solution. Food consumption was monitored 1 and 2 hr after food presentation. L-NO Arg administration produced a dose-dependent reduction in food intake. Pretreatment with metergoline (2 mg/kg) but not with ritanserin (1 mg/kg) antagonized the anorectic effect of L-NO Arg. Moreover, in the diencephalon L-NO Arg significantly reduced NO synthase activity whereas it increased serotonin levels. Our data indicate that NO might have a physiological role in the regulation of food intake and suggest that brain NO may modulate the central serotoninergic system.

Amino Acid Oxidoreductases↗

PubMed1994

Reduction of myocardial infarct size in rat by IRFI-048, a selective analogue of vitamin E.

The effects of IRFI-048 (2,3-dihydro-5-methoxy-4,6,7-trimethyl-2-benzofuranyl acetic acid), a selective analogue of Vitamin E, on myocardial tissue injury were examined in anaesthetized rats subjected to 60-min occlusion of the left coronary artery followed by 60-min reperfusion. Infarct size (Evan's blue and tetrazolium stain), serum creatinphosphokinase (CPK), plasma malonaldehyde (MAL), cardiac myeloperoxidase (MPO) activity, and ST-segment of electrocardiogram (ECG) and survival rate were evaluated. Postischaemic reperfusion produced severe cardiac necrosis, caused neutrophil (PMNs) infiltration (evaluated by MPO activity) in the jeopardized tissue, increased serum CPK and plasma MAL, raised ST-segment of ECG, and decreased survival rate. IRFI-048, (200 and 400 mg/kg o.s.) given to the rats 6 h before occlusion, caused a reduction of necrotic area expressed as a percentage of either the area at risk or the total left ventricle, decreased MPO activity both in the area at risk (from 3.2 +/- 0.3 U x 10(-3)/g tissue to 1.1 +/- 0.4 U x 10(-3)/g tissue; p < .005) and in the necrotic area (from 5.7 +/- 0.9 U x 10(-3)/g tissue to 1.8 +/- 0.5 U x 10(-3)/g tissue; p < .001), attenuated the rise of ST-segment of ECG (from 0.51 +/- 0.14 mV in the vehicle group to 0.28 +/- 0.11 mV in the treated group; p < .005), reduced the increase of plasma MAL and serum CPK during reperfusion (from 42 +/- 5.3 nmol/ml to 15 +/- 3.1 nmol/ml and 139 +/- 13 IU/100 ml to 58 +/- 7.5 IU/100 ml, respectively; p < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1994

Mediation by nitric oxide formation in the preoptic area of endotoxin and tumour necrosis factor-induced inhibition of water intake in the rat.

1. Drinking was induced in rats by 24 h of water deprivation. Water intake (ml) was evaluated for a 1 h period. 2. NG-nitro-L-arginine methyl ester (L-NAME, 5-10 micrograms, i.c.v., 50-100 ng into the preoptic area (POA)), an inhibitor of nitric oxide (NO) synthase, and methylene blue (50-100 ng into POA), an inhibitor of guanylate cyclase activation, antagonized the inhibition of drinking induced by E. coli endotoxin (LPS, 640 micrograms kg-1, i.v.) and tumour necrosis factor (TNF alpha, 40 ng, i.c.v.) in 24 h water-deprived rats. 3. L-Arginine (25, 50 and 100 ng), the precursor amino acid of NO, but not the stereoisomer D-arginine (100 ng), inhibited drinking induced by water deprivation when injected into the POA 30 min before water presentation (74.4% of inhibition with the highest dose). A dose of 12.5 ng L-arginine into the POA did not exhibit antidipsogenic effects. 4. TNF alpha (20 and 40 ng, i.c.v.; 1.25, 2.5 and 5 ng into the POA) showed a dose-dependent and powerful inhibition of drinking behaviour in water-deprived rats (70.4% and 80.8%, i.c.v. and into POA, with the highest doses, respectively). A dose of 10 ng of TNF alpha given i.c.v. had no effect on the intake of water. 5. LPS and TNF alpha, given at doses (160 micrograms kg-1, i.v. and 10 ng, i.c.v., respectively) that did not influence drinking in water-deprived rats, exhibited a strong antidipsogenic effect in water-deprived rats treated with a dose of L-arginine (12.5 ng, into the POA) which did not modify drinking by itself. (LPS + L-arginine:53.6% of inhibition; TNFalpha + L-arginine: 52.0% of inhibition).6. These results suggest that NO into the POA: (1) acts as an inhibitory mechanism on thirst and (2)plays a role in the antidipsogenic effect of LPS and TNFalpha.

Animals↗

PubMed1994

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.

Acetylcholine↗

PubMed1994

Role of tumor necrosis factor-alpha in acute hypovolemic hemorrhagic shock in rats.

Hemorrhagic shock was induced in male anesthetized rats by intermittently withdrawing blood from an iliac catheter until mean arterial blood pressure (MAP) fell and stabilized within the range of 20-30 mmHg. Survival rate, MAP, and serum and macrophage levels of tumor necrosis factor-alpha (TNF-alpha) were then evaluated. Furthermore, in ex vivo studies, the responsiveness to phenylephrine (PE; 1 nM to 10 microM) was investigated in aortic rings from hemorrhagic shocked rats. Antibodies raised against TNF-alpha (anti-TNF-alpha; 2 mg/kg) or vehicle (phosphate-buffered saline, 1 ml/kg) were injected intravenously 3 h before the bleeding. Vehicle-treated rats, subjected to hemorrhagic shock, exhibited acute and serious hypotension (MAP = 20-30 mmHg) and high levels of serum (790 +/- 47 pg/ml) and macrophage (78 +/- 9 pg/ml) TNF-alpha and died within 30 min. Moreover, aortas from shocked rats showed a marked hypocontractility to PE compared with the reactivity of aortas from a group of sham shocked rats. Anti-TNF-alpha administration significantly improved survival rate and MAP in hypovolemic shocked rats. Furthermore, the hyporesponsiveness to PE was significantly restored in aortic rings. Therefore, these data suggest that TNF-alpha is an important mediator in the pathophysiology of hypovolemic hemorrhagic shock and it might be responsible, at least in part, for the vascular hyporeactivity of this experimental circulatory shock.

Acute Disease↗

PubMed1994

Protective effects of IRFI-016, a new antioxidant agent, in myocardial damage, following coronary artery occlusion and reperfusion in the rat.

The new free radical scavenger IRFI-016 [2(2,3-dihydro-5-acetoxy 4,6,7-trimethyl-benzofuranyl) acetic acid] was assessed in a rat model of myocardial injury induced by 1 h of left coronary artery occlusion followed by 30 min of reperfusion. Myocardial ischaemia plus reperfusion (MI/R) produced severe cardiac necrosis, neutrophil infiltration in the jeopardized tissue, increased serum creatine kinase (CK) and ST segment of the electrocardiogram (ECG), lowered the pressure rate index (PRI), increased serum levels of tumour necrosis factor (TNF-alpha) and caused a decrease in the survival rate. Administration of IRFI-016 (100 and 200 mg/kg i.p.) 30 min before occlusion resulted in a significant protective effect in post-ischaemic reperfusion. Compared with untreated rats, IRFI-016, in particular the dose of 200 mg/kg, caused a reduction of the necrotic zone whether the necrotic area was expressed as a percentage of the area at risk (55 +/- 4% in the MI/R vehicle group and 24 +/- 2.5% in the MI/R treated group; p < 0.001) or as a percentage of the total left ventricle (23 +/- 3.4% in the MI/R vehicle group and 8 +/- 2.1% in the MI/R treated group; p < 0.005), reduced the myeloperoxidase activity, an index of neutrophil infiltration in the necrotic area (from 4.8 +/- 0.8 to 1.6 +/- 0.4 U/g tissue; p < 0.005), reduced the serum levels of TNF-alpha (from 216 +/- 13 to 45 +/- 7 U/ml; p < 0.001), blunted the rise of the ST segment of the ECG (from 0.47 +/- 0.13 mV in the vehicle group to 0.3 +/- 0.18 mV in the treated group; p < 0.001), reduced the loss of CK (from 220 +/- 15 to 88 +/- 13 IU/ml of blood; p < 0.001) and improved the depressed PRI (from 56 +/- 4% to 78 +/- 3% mm Hg/beats/min; p < 0.005). Finally, IRFI-016 significantly enhanced the survival rate evaluated at the end of the experiment. The results strongly indicate that IRFI-016 is a promising drug for cardiac ischaemia and reperfusion.

Animals↗

PubMed1994

Evidence for a role of platelet activating factor in hypovolemic shock in the rat.

An extremely severe circulatory shock was produced in two different manners in urethane-anaesthetized rats in order to evaluate the key role of platelet-activating factor (PAF) and myocardial depressant factor (MDF) in low flow states. Haemorrhagic shock was induced by intermittently withdrawing about 50% of the estimated blood volume until mean arterial blood pressure (MAP) stabilized in the range of 20-25 mmHg. Vehicle-treated shocked rats died within 20-30 min after the last bleeding and exhibited elevated plasma activity of MDF (159.6 +/- 7.4 U/ml). Treatment with a specific PAF receptor antagonist, L-659,989, at doses of 500 or 1000 nmol/kg i.v., significantly increased survival rate, blunted the rise in plasma MDF activity and maintained MAP at higher values compared to vehicle shocked rats. Similarly, in another group of rats PAF (15 nmol/kg, i.v.) produced a shock-like state characterized by a serious hypotension in the range of 20-30 mmHg, elevated plasma MDF activity (79.7 +/- 7,7 U/ml) and death within 20-25 min after administration. L-659,989, given 5 min after the PAF-induced sharp decrease of MAP, improved survival rate, ameliorated MAP and reduced plasma levels of MDF. The results of this study, therefore, confirm that PAF plays a role in cardiovascular changes of hypovolemic circulatory shock both directly and by inducing the release of other factors such as MDF.

Animals↗

PubMed1993

Tumor necrosis factor involvement in myocardial ischaemia-reperfusion injury.

The role of tumor necrosis factor-alpha was investigated in an anaesthetized rat model of coronary artery ligation (60 min) and reperfusion (MI/R). Sham-occluded rats (sham MI/R) were used as controls. Survival rate, myocardial necrosis, myocardial myeloperoxidase activity, serum creatinine kinase activity and serum and macrophage tumor necrosis factor-alpha were studied. Ischaemia-reperfusion injury significantly reduced survival rate (45%), produced marked myocardial injury, increased serum creatinine kinase activity and increased myocardial myeloperoxidase activity in the area-at-risk and in the necrotic area. Serum tumor necrosis factor-alpha was undetectable during the occlusion period, but increased significantly upon release of the coronary artery. At the end of reperfusion, macrophage tumor necrosis factor-alpha was also increased. Passive immunization with a hyperimmune serum containing antibodies against murine tumor necrosis factor-alpha significantly increased survival rate (80%), lowered myocardial necrosis, reduced the increase in serum creatinine kinase activity and decreased myeloperoxidase activity in the area-at-risk and in the necrotic area. These data are consistent with an involvement of tumor necrosis factor-alpha in myocardial ischaemia-reperfusion injury.

Animals↗

PubMed1993

Anorectic activity of NG-nitro-L-arginine, an inhibitor of brain nitric oxide synthase, in obese Zucker rats.

We investigated the effects of NG-nitro-L-arginine (L-NO Arg) administration (12.5, 25 and 50 mg/kg i.p.) on food consumption and body weight of male obese Zucker rats (fa/fa) and in their lean age-matched controls (FA/?; FA/FA), both groups aged 14 weeks. Acute or repeated administration of L-NO Arg reduced food intake and body weight in both obese and lean rats. However the lean rats showed tolerance to the L-NO Arg effects after 5 days of treatment. L-NO Arg anorexia was suppressed by pretreatment with metergoline. These results suggest that L-NO Arg may represent a new anorectic drug.

Amino Acid Oxidoreductases↗