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Biomedical subjects

P Ghezzi

Publications and source records attributed to P Ghezzi.

At least 163 records · Page 9Linked to original sources
PubMed1985

Platelet derived growth factor induces ornithine decarboxylase activity in NIH 3T3 cells.

Incubation with highly purified human Platelet Derived Growth Factor induced ornithine decarboxylase activity in quiescent NIH 3T3 cells concomitantly with mitogenic stimulation. Pretreatment of cells with a specific ornithine decarboxylase inhibitor, DL-alpha-difluoromethyl-ornithine significantly inhibited the effect of the mitogen on DNA synthesis. These experiments suggest that the mitogenic activity of Platelet Derived Growth Factor, similarly to that of other serum growth factors or tumor promoters, is mediated through rise in polyamine levels.

Animals↗
PubMed1985

Rapid killing of actinomycin D-treated tumor cells--cytotoxicity of cell-free monocyte supernatants.

Human monocytes kill Actinomycin D-treated WEHI 164 sarcoma cells in a 6 h 51Cr release assay (drug dependent cellular cytotoxicity, DDCC). In the present study we have investigated and characterized the human monocyte production of a cytotoxic factor which mediates DDCC. Cell-free supernatants obtained culturing monocytes for 4-5 h kill Actinomycin D-treated WEHI 164 cells but not untreated tumor cells. A series of antiproteases inhibits the cytotoxic activity of cell-free monocyte supernatants, whereas scavengers of reactive oxygen intermediates were ineffective. The lytic activity was destroyed treating supernatants at 100 degrees C for 5 min or by exposure to acid pH or to proteinase K, whereas it was unaffected by heating at 56 degrees C for 30 min. Upon gel filtration on Sephacryl S200, cytolytic activity eluted in the 33,000 molecular weight range.

Catalase↗
PubMed1985

Kinetics of monosodium glutamate in human volunteers under different experimental conditions.

The kinetics of glutamic acid (GA) in plasma was studied in human volunteers after administration of monosodium glutamate (MSG) at different doses--43 mg/kg (3 g/70 kg) and 64 mg/kg (4.5 g/70 kg)--and in bouillon solutions of different concentrations (1.5-3.5%). MSG was administered to the subjects either during fasting or immediately after a standard meal. In the fasted subjects MSG administration caused a dose-dependent increase in plasma GA levels. In contrast, ingestion of MSG with a meal did not result in any significant increases in plasma GA levels in comparison with the wide variations observed in plasma GA after ingestion of a meal without added MSG.

Adult↗
PubMed1985

Role of reactive oxygen intermediates in the interferon-mediated depression of hepatic drug metabolism and protective effect of N-acetylcysteine in mice.

Interferon (IFN) and IFN inducers are known to depress hepatic microsomal cytochrome P-450 levels, and the liver toxicity of IFN was reported to be lethal in newborn mice. We have observed that administration to mice of IFN and IFN inducers caused a marked increase in liver xanthine oxidase activity. Because this enzyme is well known to produce reactive oxygen intermediates and cytochrome P-450 was reported to be sensitive to the oxidative damage, we have tested the hypothesis that a free radical mechanism could mediate the depression of cytochrome P-450 levels by IFN. Administration to mice of the IFN inducer polyinosinic-polycytidylic acid (2 mg/kg i.p.) caused a 29 to 52% decrease in liver cytochrome P-450. Concomitant p.o. administration of the free radical scavenger, N-acetylcysteine (as a 2.5% solution in drinking water), or the xanthine oxidase inhibitor, allopurinol (100 mg/kg), protected against the IFN-mediated depression of P-450 kg), protected against the IFN-mediated depression of P-450 levels. The results suggest that an increased endogenous generation of free radicals, possibly due to the induction of xanthine oxidase, is implicated in the IFN-mediated depression of liver drug metabolism. The relevance of these data also extends to cases in which this side effect is observed in pathological situations (e.g., viral diseases and administration of vaccines) associated with an induction of IFN.

Acetylcysteine↗
PubMed1984

Enhanced xanthine oxidase activity in mice treated with interferon and interferon inducers.

Administration to mice of either interferon (IFN) or IFN inducers resulted in a marked increase of xanthine oxidase (XO) activity in different organs. Dose response studies revealed that serum XO was increased by administration of polyinosylic-polycyticylic acid (poly I-C) at doses as low as 0.1 mg/kg. In view of the well known ability of XO to generate superoxide radicals it is suggested that its induction might play a role in several biological effects of IFN.

Animals↗
PubMed1983

N-acetyl-beta-D-glucosaminidase (NAG) and NAG isoenzymes in children with upper and lower urinary tract infections.

The use of N-acetyl-beta-D-glucosaminidase (NAG) to diagnose the site of urinary tract infection was studied in pediatric patients. Differentiation between upper and lower tract infections (UTI) was based on clinical grounds and on elevated erythrocyte sedimentation rate, C-reactive protein and fever. NAG excretion expressed as nmol X h-1 X mg-1 of urinary creatinine was higher in children with upper UTI (mean +/- SE 906 +/- 236) than in those with lower UTI (145 +/- 23) or healthy children (151.6 +/- 10) (p less than 0.01 by Duncan's test). In children with upper UTI, NAG excretion fell in parallel with the remission due to antibiotic treatment. This however was not seen in children treated with aminoglycosides. A specific and significant elevation (p less than 0.01) of the B isoenzyme of NAG was documented in children with upper UTI but not in those with lower UTI (B form in upper UTI 49.2% +/- 3.9 versus 21.9 +/- 3.3 in lower UTI; healthy children 18.9 +/- 3.4). The percentage of B isoenzyme excreted was high in two children with upper UTI but was low total NAG urinary excretion, suggesting that the quantification of isoenzymes offers further specificity in diagnosis. We conclude that the measurement of NAG and its isoenzymes in children with UTI provides useful information in the diagnosis of the site of infection.

Acetylglucosaminidase↗
PubMed1983

Regulation of the macrophage content of neoplasms by chemoattractants.

Factor chemotactic for mononuclear phagocytes was found in supernatant fluids of cultured human and mouse tumor cells. In 11 mouse tumors there was a correlation observed between chemotactic activity and macrophage content of neoplastic tissues. Tumor-derived chemoattractants appear to participate in the regulation of tumor-associated macrophages.

Animals↗
PubMed1983

Pyroglutamate kinetics and neurotoxicity studies in mice.

Plasma and brain kinetics of L-glutamic (GA) and L-pyroglutamic (PY) acids were studied after oral administration of monosodium glutamate (MSG) or pyroglutamate to adult mice. Oral MSG (0.5 g/kg) increased plasma GA and PY levels 4.5 and 1.8 times, respectively. A small increase in brain PY (1.3 times the basal level) but not in brain GA, was observed. Oral administration of pyroglutamate (0.5 g/kg) increased plasma PY levels 56 times in adult mice and 69 times in infant mice. No lesions in the arcuate nucleus of the hypothalamus were observed when pyroglutamate was administered orally to infant mice at doses of 2 and 4 g/kg.

Animals↗
PubMed1983

Plasma pyroglutamic acid levels after oral administration of monosodium glutamate to human volunteers.

Plasma levels of pyroglutamic (PY) and glutamic (GA) acids have been measured after oral administration of monosodium glutamate (MSG) to 6 human volunteers. MSG (43 mg/kg) was administered either after an overnight fast or immediately after a normal meal. In fasting subjects plasma GA peak levels were about 2.3 times the basal levels whereas the increase in plasma PY levels were only 1.5-fold. When MSG was administered with a meal plasma GA levels were raised, to a lesser extent, while no increase could be observed in plasma PY.

Administration, Oral↗
PubMed1983

Dissociation between macrophage tumoricidal capacity and suppressive activity: analysis with macrophage-defective mouse strains.

Macrophages (M phi diameter) from three mouse strains with genetically distinct M phi diameter deficits (C3H/HeJ, A/J, and P/J) were unable to develop high cytolytic and cytotoxic activity against tumor cells in vitro when exposed to agents (MAF and IFN-beta) that strongly increased the tumoricidal capacity of M phi diameter from nondefective C3H/HeN mice. Nevertheless, the tumoricidal deficits of M phi diameter from the defective strains did not affect their suppressive capacity on Con A-induced lymphoproliferation, nor their ability to react to IFN-beta by decreasing suppressive activity. In fact, natural suppressive activity and IFN-beta-induced changes in the suppression of M phi diameter from C3H/HeJ, A/J, and P/J mice were highly comparable to those of C3H/HeN M phi diameter, thus stressing the dissociation between the mechanisms governing M phi diameter suppression and M phi diameter tumoricidal activity. Analysis of the modulation by MAF and IFN-beta of M phi diameter ability to release the oxygen metabolites O2- and H2O2, molecules possibly involved in the effector mechanism of both M phi diameter cytotoxicity and suppression, revealed a close correlation with the patterns of suppressive activity in both nondefective and defective strains. In contrast, no correlation between the production of oxygen-reactive species and M phi diameter tumoricidal activity was observed. The ability of MAF- and IFN-beta-treated M phi diameter to produce PGE, a molecule of major importance in M phi diameter-mediated suppression and possibly involved also in the regulation of M phi diameter tumoricidal activity, again paralleled M phi diameter suppressive capacity. Thus, the mechanisms controlling M phi diameter antitumor activity appeared to be clearly distinct from those involved in M phi diameter suppression.

Animals↗
PubMed1983

Interferon decreases production of hydrogen peroxide by macrophages: correlation with reduction of suppressive capacity and of anti-microbial activity.

Mouse peritoneal macrophages (M phi) expressed enhanced tumoricidal activity upon in vitro stimulation either with the lymphokine M phi-activating factor (MAF) or with fibroblast interferon (IFN-beta). In contrast, M phi suppressive activity on lymphoproliferation was not affected by MAF pretreatment, but was drastically reduced or abolished by IFN-beta. Catalase, the enzyme involved in the destruction of hydrogen peroxide (H2O2), did significantly decrease M phi suppressive capacity but had no effect on M phi tumoricidal activity. Analysis of the phagocytosis-dependent H2O2 production by IFN-beta-treated M phi demonstrated a strong impairment of the oxygen metabolite release, which strictly paralleled the decreased M phi suppressive capacity. On the other hand, MAF did not modify H2O2 release by M phi. Studies on M phi antibacterial activity against Salmonella typhimurium, a function thought to depend upon H2O2 production, showed that exposure of M phi to IFN-beta significantly impaired their bactericidal and bacteriostatic capacity, again in close correlation with the decrease in H2O2 production. Thus, IFN-beta appears as modulating both suppressive and antibacterial capacities of M phi through reduction of their oxygen metabolism, whereas regulation of M phi anti-tumour activity is possibly controlled by different mechanisms.

Animals↗
PubMed1982

Plasma and brain levels of glutamate and pyroglutamate after oral monosodium glutamate to rats.

Plasma and brain levels of pyroglutamate (Py), a compound connected with the pathway of glutamate (GA) metabolism, were measured in rats after oral administration of monosodium glutamate (MSG) or Py. Oral MSG (1 g/kg) was followed by only a small rise in plasma Py levels. No increase of Py or GA brain levels was observed in these experimental conditions. Oral administration of Py (0.05, 0.5 and 1 g/kg) resulted in a marked dose-dependent increase of plasma Py, but no increase of plasma or brain GA levels. However, Py accumulated in brain in a dose-related manner. After 0.05 mg/kg the basal brain levels remained unchanged at all the times considered. Rat brain Py levels significantly increased when the oral dose of Py was raised to 0.5 g/kg. Peak brain levels were reached at 240 min, and were about 3 and 4 times the basal levels after 0.5 and 1 g/kg, respectively.

Administration, Oral↗
PubMed1982

IFN-beta-induced reduction of superoxide anion generation by macrophages.

Resident mouse peritoneal macrophages (M phi) produced significant amounts of superoxide anion (O2-) in response to phagocytic stimuli. When M phi were exposed in vitro for 20 hr to fibroblast interferon (IFN-beta), their capacity to release O2- was significantly reduced, such reduction being more evident with increasing IFN-beta concentrations. In contrast, O2- production by M phi exposed for 20 hr to the lymphokine macrophage activating factor (MAF) or treated with either MAF or IFN-beta for 4 hr was not significantly different from that of control cells. This pattern of activity closely followed that of M phi-mediated suppression of lymphocyte proliferation, which was dramatically reduced by 20 hr exposure of M phi to IFN-beta, but unchanged by treatment with MAF. No correlation was however found between superoxide anion generation and enhancement of tumoricidal capacity in IFN-beta-treated M phi. We thus concluded that O2- does not play a relevant role in IFN-beta-induced M phi cytolysis, whereas the reduction of O2- production could be of major importance in the decrease of M phi suppression induced by IFN-beta.

Animals↗
PubMed1980

Monosodium glutamate kinetic studies in human volunteers.

(a) A kinetic study of plasma glutamic acid (GA) was made after monosodium glutamate (MSG) administration to human volunteers. MSG was given at doses of 30,60 and 120 mg/kg in a bouillon and of 60 mg/kg in tomato juice. In another experiment a normal meal was consumed without added MSG. (2) Plasma area under the curve (AUC) was found to be lower in females than in males. (3) Plasma AUC was lower when MSG was taken in tomato juice than when consumed in bouillon. (4) Consumption of the normal meal did not result in any significant increase in plasma GA.

Adult↗