Papers by Giuseppe M Campo
International journal of microcirculation, clinical and experimental / sponsored by the European Society for Microcirculation
It has been suggested that leukocyte adhesion mechanisms play a key role in experimental myocardi... more It has been suggested that leukocyte adhesion mechanisms play a key role in experimental myocardial infarction. We have recently shown that E-selectin, an adhesion molecule belonging to the selectin family, is involved in the pathogenesis of experimental myocardial ischemia. We investigated the circulating levels of E-selectin, studied as a marker of endothelial dysfunction, in acute myocardial infarction. Our study was carried out in 60 patients, 20 hospitalized for acute myocardial infarction, 20 suffered from angina pectoris and 20 healthy control subjects. Patients with acute myocardial infarction had increased serum levels of soluble E-selectin (sE-selectin = 255 +/- 12 ng/ml) compared to both patients with angina pectoris (sE-selectin = 51 +/- 14 ng/ml). Thrombolytic therapy with urokinase (1,000,000 IU as an intravenous bolus in 5 min, followed by producing reperfusion and reduced the serum levels of sE-selectin (71 +/- 19 ng/ml). Our results confirm previous experimental dat...
Drugs under experimental and clinical research, 1993
Restoration of blood flow after an ischaemic event generates the formation of oxygen radicals whi... more 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, resp...
Innate Immunity, 2013
Purpose: To evaluate the effect of aminoacid enriched artificial tears on the ocular surface of p... more Purpose: To evaluate the effect of aminoacid enriched artificial tears on the ocular surface of patients with dysfunctional tear syndrome (DTS). Methods: Forty patients were divided into two groups: group 1 treated for 90 days with sodium hyaluronate (SH) 0.15% 1 drop · 5 times ⁄ day; group 2 treated for 90 days with SH 0.15% + aminoacids mixture 1 drop · 5 times ⁄ day. Symptom score questionnaire, tear break-up time (TBUT), corneal fluorescein stain, Shirmer's I test and confocal microscopy were performed at baseline and after 30 and 90 days. Confocal images underwent morphometric analysis. Results: Both treatments improved symptoms after 1 month. Group 2 patients showed at 1 month an improvement of TBUT and corneal stain, maintained throughout the study. Also Shirmer's I test improved after 3 months. In group 1, an improvement of TBUT and corneal stain was observed after 3 months. The morphometric analysis of confocal images demonstrated at month 1 an improvement of nerve tortuosity in group 2; after 3 months both groups showed a significant improvement versus baseline. The epithelium showed, in both groups, a reduction in hyperreflective large cells starting from 1 month; the area of the cells was significantly reduced after 3 months, with a significant higher reduction in group 2. The perineural stromal opacity was significantly increased after 3 months, particularly in group 2. Conclusion: This is the first study addressing corneal changes after amino acids administration in a DTS population. The treatment with amino acids enriched SH can be considered a useful tool in the treatment of DTS.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2005
The main role of superoxide dismutases (SODs) is to eliminate reactive oxygen species in cells an... more The main role of superoxide dismutases (SODs) is to eliminate reactive oxygen species in cells and tissues. Extracellular SOD (EC-SOD/SOD3) is a major superoxide scavenger and it is located on cell surfaces and primarily in extracellular matrix, and binds heparan sulfates by its carboxyterminal portion. Human EC-SOD gene is located on chromosome 4 and comprises three exons and two introns. The SOD3 coding sequence is entirely located within exon 3 and has missense polymorphisms. The Arg213Gly mutation affects the function of the carboxyterminus and correlates with several diseases. In this work, we explored genetic variants within EC-SOD gene of subjects living in southern Italy. Four new variations were detected: one was silent mutation, while three were missense variations that give rise to amino acid substitutions at position 131 (F>C), 160 (V>L) and 202 (R>L) in the mature product. The Arg213Gly variant was not found. The missense mutations in the DNA of assayed 2400 chromosomes had frequencies of 5.34% for the F131C variation, 0.25% for the V160L variation and 0.84% for the R202L variation. The effect of these alterations on the metabolic activity and diseases remains to be further explained.
Therapeutic Drug Monitoring, 1993
The effect of the selective serotonin reuptake inhibitor fluvoxamine (100 mg/day for 10 consecuti... more The effect of the selective serotonin reuptake inhibitor fluvoxamine (100 mg/day for 10 consecutive days) on the kinetics of a single oral dose of imipramine (50 mg) and desipramine (100 mg) was investigated in 12 healthy subjects. Compared with a control session, treatment with fluvoxamine caused a significant prolongation of imipramine half-life (from 22.8 +/- 6.4 to 40.5 +/- 5.0 h, means +/- SD, p < 0.01) and a marked decrease in imipramine apparent oral clearance (from 1.02 +/- 0.19 to 0.28 +/- 0.06 L/h/kg, p < 0.0001). No significant changes in desipramine kinetics were observed during fluvoxamine treatment. These findings indicate that, at the dosage tested, fluvoxamine markedly inhibits the demethylation of imipramine without affecting significantly the CYP2D6-mediated hydroxylation of desipramine.
Therapeutic Drug Monitoring, 1992
We describe four patients in whom the addition of fluvoxamine (100 mg/day) to the treatment with ... more We describe four patients in whom the addition of fluvoxamine (100 mg/day) to the treatment with imipramine or desipramine (100-150 mg/day) resulted in a dramatic increase in the plasma concentrations of the tricyclic antidepressants associated with adverse effects. These observations indicate that fluvoxamine inhibits both the demethylation of imipramine and, possibly to a lesser extent, the hydroxylation of desipramine. The combination of fluvoxamine with tricyclic antidepressants should be avoided whenever possible.
International Journal of Microcirculation, 1997
The aim of our study was to investigate the vascular effects of recombinant human granulocyte col... more The aim of our study was to investigate the vascular effects of recombinant human granulocyte colony-stimulating factor (rh G-CSF) in a rat model of irreversible vascular failure. Male anesthetized rats were subjected to the clamping of the splanchnic arteries for 45 min. This surgical procedure resulted in an irreversible state of shock (splanchnic artery occlusion shock) characterized by high mortality
Inflammation Research, 1996
We investigated the role played by monocytes and lymphocytes in the pathogenesis of experimental ... more 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
Journal of Pharmacy and Pharmacology, 1999
The plant Hypericum perforatum is used in folk medicine to treat several diseases and research at... more The plant Hypericum perforatum is used in folk medicine to treat several diseases and research attention has been recently focused on its antidepressant action. Hypericin and avonoids are the most important constituents of the plant, but the exact role of these compounds in the effects of hypericum on mood disorders is not well known. We have investigated the contribution of these compounds to the antidepressant effects of hypericum.
Cell Biochemistry and Function, 2014
The aim of this study was to investigate the involvement of exchange proteins directly activated ... more The aim of this study was to investigate the involvement of exchange proteins directly activated by cyclic adenosine (ADO) monophosphate (EPAC) in 4-mer hyaluronan (HA) oligosaccharide-induced inflammatory response in mouse normal synovial fibroblasts (NSF). Treatment of NSF with 4-mer HA increased Toll-like receptor-4, TNF-alpha and IL-1beta mRNA expression and of the related proteins, as well as nuclear factor kappaB (NF-kB) activation. Addition to NSF, previously stimulated with 4-mer HA oligosaccharides, of ADO significantly reduced NF-kB activation, TNF-alpha and IL-1beta expression. The pre-treatment of NSF with cyclic ADO monophosphate and/or PKA and/or EPAC-specific inhibitors significantly inhibited the anti-inflammatory effect exerted by ADO. In particular, the EPAC inhibitor reduced the ADO effect to a major extent than the PKA inhibitor. These results mean that both PKA and EPAC pathways are involved in ADO-induced NF-kB inhibition although EPAC seems to be more involved than PKA.
Life Sciences, 2004
We investigated the Levetiracetam (LVT) ability to protect the brain against kainic acid (KA) ind... more We investigated the Levetiracetam (LVT) ability to protect the brain against kainic acid (KA) induced neurotoxicity. Brain injury was induced by intraperitoneal administration of KA (10 mg/kg). Sham brain injury rats were used as controls. Animals were randomized to receive either LVT (50 mg/kg) or its vehicle (1 ml/kg) 30 min. before KA administration. Animals were sacrificed 6 hours after KA injection to measure brain malonildialdehyde (MDA), glutathione levels (GSH) and the mRNA for interleukin-1h (IL-1h) in the cortex and in the diencephalon. Behavioral changes were also monitored. Intraperitoneal administration of LVT decreased significantly MDA in the cortex (KA + vehicle = 0.25 F 0.03 nmol/mg protein; KA + LVT = 0.13 F 0.01 nmol/mg protein; P < 0.005), and in the diencephalons (KA + vehicle = 1,01 F 0.2 nmol/mg protein; KA + LVT = 0,33 F 0,08 nmol/mg protein; P < 0.005), prevented the brain loss of GSH in both cortex (KA + vehicle = 5 F 1 Amol/g protein; KA + LVT = 15 F 2 Amol/g protein; P < 0.005) and diencephalons (KA + vehicle = 9 F 0.8 Amol/g protein; KA + LVT = 13 F 0.3 Amol/g protein; P < 0.05), reduced brain IL-1h mRNA and markedly controlled seizures. Histological analysis showed a reduction of cell damage in LVT treated samples. The present data indicate that LVT displays neuroprotective effects against KA induced brain toxicity and suggest that these effects are mediated, at least in part, by inhibition of lipid peroxidation. D
Arthritis Research & Therapy, 2003
To evaluate the antioxidant activity of the glycosaminoglycans hyaluronic acid (HYA) and chondroi... more To evaluate the antioxidant activity of the glycosaminoglycans hyaluronic acid (HYA) and chondroitin-4-sulphate (C4S), we used a rat model of collagen-induced arthritis (CIA). Arthritis was induced in Lewis rats by multiple intradermal injections of 250 μl of emulsion containing bovine type II collagen in complete Freund's adjuvant at the base of the tail and into three to five other sites
Surgery, 2001
Impaired wound healing is a well-documented phenomenon in experimental and clinical diabetes. Eme... more Impaired wound healing is a well-documented phenomenon in experimental and clinical diabetes. Emerging evidence favors the involvement of free radicals in the pathogenesis of diabetes-related healing deficit. This study assessed the effect of systemic administration of raxofelast, a protective membrane antioxidant agent, on wound healing by using healing-impaired (db/db) mice. The wound healing effect of raxofelast was investigated by using an incisional skin-wound model produced on the back of female diabetic C57BL/KsJ db+/db+ mice and their healthy littermates (db+/+m). Animals were then randomized to the following treatment: raxofelast (15 mg/kg/d intraperitoneally) or its vehicle (dimethyl sulfoxide/sodium chloride 0.9%, 1:1, vol/vol). The animals were killed on different days, and the wounded skin tissues were used for histologic evaluation and for analysis of malondialdehyde (MDA) level and myeloperoxidase (MPO) activity, wound breaking strength, and collagen content. Diabetic mice showed delayed wound healing together with low collagen content, breaking strength, and increased MDA levels and MPO activity when compared with their healthy littermates. The administration of raxofelast did not modify the process of wound repair in healthy (db/+) mice, but significantly improved impaired wound healing in diabetic mice through the stimulation of angiogenesis, reepithelialization, synthesis, and maturation of extracellular matrix. Furthermore, raxofelast treatment significantly reduced MDA levels, MPO activity, and increased the breaking strength and collagen content of the wound. The current study provides evidence that raxofelast restores wound healing to nearly normal levels in experimental diabetes-impaired wounds and suggests that an increased lipid peroxidation in diabetic mice may have a role in determining a defect of wound repair.
Shock, 1997
In the present study we tested the hypothesis that nitric oxide may play a role in the pathogenes... more 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.
Science of The Total Environment, 2008
In order to gain more knowledge on the stress responses of gilhead seabream (Sparus aurata) under... more In order to gain more knowledge on the stress responses of gilhead seabream (Sparus aurata) under extreme conditions, this study investigated the functional properties of the hemoglobin system and globin gene expression under hypoxia and low salinity. The oxygen affinity for the two hemoglobin components present inside the S. aurata erythrocyte was practically identical as was the influence of protons and organic phosphates (Root effect). The quantification of S. aurata hemoglobin fractions performed by HPLC and the data on gene expression of globin chains assayed by PCR indicate that under hypoxia and low salinity there is a change in the ratio between the two different hemoglobin components.
Pancreas, 2004
Several reports have described a loss of endogenous antioxidants and molecular oxidative damage d... more Several reports have described a loss of endogenous antioxidants and molecular oxidative damage during acute pancreatitis. Since hyaluronic acid and chondroitin-4-sulfate possess antioxidant properties, the effect of the administration of these glycosaminoglycans in a cerulein-induced acute pancreatitis in rats was investigated. Cerulein administration produced pancreatic edema and a marked increase in serum lipase and amylase activity; induced a severe depletion of reduced glutathione, catalase, and superoxide dismutase levels; primed lipid peroxidation; and promoted neutrophil intervention. Intraperitoneal pretreatment of rats with hyaluronic acid or chondroitin-4-sulfate or with both compounds ameliorated pancreatic cell conditions; restored the endogenous antioxidants reduced glutathione, catalase and superoxide dismutase; limited cell membrane peroxidation; and reduced neutrophil activation. Our data confirm the antioxidant activity of these 2 glycosaminoglycans.
Life Sciences, 2004
Oxidative stress is involved in the pathogenesis of chemically mediated liver injury. Since glyco... more Oxidative stress is involved in the pathogenesis of chemically mediated liver injury. Since glycosaminoglycans possess antioxidant activity, the aim of this work was to assess the protective effects of hyaluronic acid and chondroitin-4-sulphate treatment in a model of carbon tetrachloride-induced liver injury. Liver damage was induced in male rats by an intraperitoneal injection of carbon tetrachloride (1ml/kg in vegetal oil). Serum alanine aminotransferase and aspartate aminotransferase, hepatic malondialdehyde, plasma TNF-a, hepatic reduced glutathione and catalase, and myeloperoxidase, an index of polymorphonuclear infiltration in the jeopardised hepatic tissue, were evaluated 24 h after carbon tetrachloride administration. Carbon tetrachloride produced a marked increase in serum alanine aminotransferase and aspartate aminotransferase activities, primed lipid peroxidation, enhanced plasma TNF-a levels, induced a severe depletion of reduced glutathione and catalase, and promoted neutrophil accumulation. Intraperitoneal treatment of rats with hyaluronic acid (25 mg/kg) or chondroitin-4-sulphate (25 mg/kg) failed to exert any effect in the considered parameter, while the combination treatment with both glycosaminoglycans (12,5 + 12,5 mg/kg) decreased the serum levels of alanine aminotransferase and aspartate aminotransferase, inhibited lipid peroxidation by reducing hepatic malondialdehyde, reduced plasma TNF-a, restored the endogenous antioxidants, and finally decreased myeloperoxidase activity. These results suggest that hyaluronic acid and chondroitin-4-sulphate possess a different antioxidant mechanism and consequently the 0024-3205/$ -see front matter D Life Sciences 74 combined administration of both glycosaminoglycans exerts a synergistic effect with respect to the single treatment. D
Journal of Molecular and Cellular Cardiology, 1998
Journal of Clinical Investigation, 1999
The recent cloning of the mouse and human obesity genes and the characterization of their protein... more The recent cloning of the mouse and human obesity genes and the characterization of their protein product, leptin (1), has introduced a new era in the field of obesity research. Leptin is a hormone exclusively produced by the adipocytes that conveys information on the size of energy stores to the brain and activates hypothalamic centers that regulate energy intake and expenditure (2). This protein also regulates feeding behavior by reducing food consumption (3, 4).
Journal of Cardiovascular Pharmacology, 1992
Splanchnic artery occlusion (SAO) shock was induced in anesthetized rats by clamping the celiac t... more 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.
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Papers by Giuseppe M Campo