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Biomedical subjects

E Giuliani

Publications and source records attributed to E Giuliani.

At least 19 recordsLinked to original sources
PubMed2001

Human platelets bind and degrade 2-arachidonoylglycerol, which activates these cells through a cannabinoid receptor.

The endocannabinoid 2-arachidonoylglycerol (2-Delta(4)Ach-Gro) activates human platelets in platelet-rich plasma at physiological concentrations. The activation was inhibited by selective antagonists of CB(1) and CB(2) cannabinoid receptors, but not by acetylsalicylic acid. Human platelets can metabolize 2-Delta(4)Ach-Gro by internalization through a high affinity transporter (K(m) = 300 +/- 30 nM, V(max) = 10 +/- 1 pmol.min(-1).mg protein(-1)), followed by hydrolysis by a fatty acid amide hydrolase (K(m) = 8 +/- 1 microM, V(max) = 400 +/- 50 pmol.min(-1).mg protein(-1)). The anandamide transport inhibitor AM404, and anandamide itself, were ineffective on 2-Delta(4)Ach-Gro uptake by platelets, whereas anandamide competitively inhibited 2-Delta(4)Ach-Gro hydrolysis (inhibition constant = 10 +/- 1 microM). Platelet activation by 2-Delta(4)Ach-Gro was paralleled by an increase of intracellular calcium and inositol-1,4,5-trisphosphate, and by a decrease of cyclic AMP. Moreover, treatment of preloaded platelet-rich plasma with 2-Delta(4)Ach-Gro induced an approximately threefold increase in [(3)H]2-Delta(4)Ach-Gro release, according to a CB receptor-dependent mechanism. On the other hand, ADP and collagen counteracted the activation of platelets by 2-Delta(4)Ach-Gro, whereas 5-hydroxytryptamine (serotonin) enhanced and extended its effects. Remarkably, ADP and collagen also reduced [(3)H]2-Delta(4)Ach-Gro release from 2-Delta(4)Ach-Gro-activated platelets, whereas 5-hydroxytryptamine further increased it. These findings suggest a so far unnoticed interplay between the peripheral endocannabinoid system and physiological platelet agonists.

Adenosine Diphosphate↗
PubMed1998

Clozapine metabolism rate as a possible index of drug-induced granulocytopenia.

A possible relationship between haematological adverse reactions and clozapine (CLZ) metabolism rate was studied. Sixteen chronic schizophrenic outpatients (mean age 34.62 years +/- 7.56 SD) were treated with CLZ, 75-600 mg/daily for 9 weeks. CLZ and norclozapine (NCLZ) plasma levels were determined weekly, contemporarily with blood cell counts. CLZ plasma levels ranged from 25 to 1270 ng/ml (mean 266.27 ng/ml +/- 197.44 SD), while NCLZ plasma levels ranged from 25 to 1280 ng/ml (mean 169.0 ng/ml +/- 127.94 SD). NCLZ/CLZ ratio ranged from 0.13 to 1.72 (mean 0.72 +/- 0.28 SD). Leukocyte count ranged from 5.2 to 18.8 10(9)/l (mean 9.37 10(9)/l +/- 2.94 SD) and neutrophil count ranged from 1.8 to 13.4 10(9)/l (mean 5.73 +/- 2.57 SD). No correlation was found between CLZ dosage and NCLZ plasma levels. Both CLZ and NCLZ plasma levels correlated positively with neutrophil count (CLZ: P = 0.001, r = 0.26; NCLZ: P = 0.01, r = 0.20). The correlation between NCLZ/CLZ plasma level ratio and neutrophil count was significantly negative (P = 0.002, r = 0.25). These preliminary data suggest that the NCLZ/CLZ ratio, as an index of CLZ metabolism, might be a possible risk factor associated with CLZ treatment.

Adult↗
PubMed1998

Clustering of endothelial markers of vascular damage in human salt-sensitive hypertension: influence of dietary sodium load and depletion.

The contributing role of vascular endothelium in the development of hypertension-related vascular damage is well accepted. Salt-sensitive hypertension is characterized by a cluster of renal, hormonal, and metabolic derangements that might favor the development of cardiovascular and renal damage. To evaluate endothelial involvement in salt-sensitive essential hypertension, plasma levels of several markers of endothelial damage such as endothelin-1 (ET-1), von Willebrand factor (vWf), and soluble (S-) adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and 24-hour urinary albumin excretion (UAE) were measured in 39 nondiabetic, nonobese, never-treated essential hypertensive patients after intermediate (120 mmol/d), high (220 mmol/d), and low (20 mmol/d) NaCl diets. Patients were classified as salt sensitive (n=18) or salt resistant (n=21) according to their blood pressure responses to changes in dietary NaCl intake. Salt-sensitive hypertensives showed higher plasma ET-1 (P<0.05), vWf (P<0.005), and S-E-selectin levels (P<0.04) and increased UAE (P<0.05) than salt-resistant hypertensives. By contrast, circulating S-ICAM-1 and S-VCAM-1 concentrations were not significantly higher in salt-sensitive (596. 56+/-177.05 ng/mL and 541.06+/-157.84 ng/mL, respectively) than salt-resistant patients (516.86+/-147.99 ng/mL and 449.48+/-158.91 ng/mL, respectively). During the intermediate NaCl diet, plasma ET-1 responses to oral glucose load were greater in salt-sensitive (P<0. 05) than in salt-resistant patients. A marked (P<0.05) hyperinsulinemic response to oral glucose load was evident in salt-sensitive but not salt-resistant patients after each diet. This study shows increased plasma levels of the endothelium-derived substances E-selectin, vWf, and ET-1 in salt-sensitive hypertensives. Our findings support the hypothesis that salt sensitivity is correlated with an increased risk for developing hypertension-related cardiovascular damage.

Adult↗
PubMed1995

Immunoresponsiveness of cancer patients: effect of blood transfusion and immune reactivity of tumor infiltrating lymphocytes.

The immunoreactivity of cancer patients submitted to surgery and perioperatively transfused was investigated. Peripheral blood mononuclear cells (PBMC) and tumor infiltrating lymphocytes (TIL) were tested for the natural killer (NK) cytotoxic activity, for the in vitro synthesis of interleukin-2 (IL-2), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2). The serum levels and the production of PGE2 by PBMC were significantly higher in patients than in controls, whereas no significant differences in the tested immunological variables emerged between the two groups of subjects. Instead, TIL produced significant larger amounts of spontaneous PGE2 (p < 0.001) and significant lower amounts of IFN-gamma (p < 0.001) and TNF-alpha (p < 0.001) than autologous PBMC, suggesting an involvement of PGE2 in the impairment of the host immunoreactivity at the tumor site. To evaluate the immunomodulating effect of blood transfusion, the patients were reexamined 8 to 20 days after surgery. No differences were found in the NK cytotoxic activity, lymphokine synthesis, serum levels, and production of PGE2 between transfused and untransfused patients. These results do not support the hypothesis that blood transfusions negatively affect the immune response of neoplastic patients.

Adult↗
PubMed1994

Protein farnesyltransferase inhibitors block the growth of ras-dependent tumors in nude mice.

The posttranslational addition of a farnesyl moiety to the Ras oncoprotein is essential for its transforming activity. Cell-active inhibitors of the enzyme that catalyzes this reaction, protein farnesyltransferase, have been shown to selectively block ras-dependent transformation of cells in culture. Here we describe the protein farnesyltransferase inhibitor 2(S)-[2(S)-[2(R)-amino-3-mercapto]propylamino-3(S)-methyl] pentyloxy-3-phenylpropionylmethioninesulfone methyl ester (L-739,749), which suppressed the anchorage-independent growth of Rat1 cells transformed with viral H-ras and the human pancreatic adenocarcinoma cell line PSN-1, which harbors altered K-ras, myc, and p53 genes. This compound also suppressed the growth of tumors arising from ras-transformed Rat1 cells in nude mice by 66%. Under the same conditions, doxorubicin inhibited tumor growth by 33%. Control tumors formed by v-raf- or v-mos-transformed Rat1 cells were unaffected by L-739,749. Furthermore, mice treated with L-739,749 exhibited no evidence of systemic toxicity. This is a demonstration of antitumor activity in vivo using a synthetic small molecule inhibitor of protein farnesyltransferase.

Alkyl and Aryl Transferases↗
PubMed1992

Prevalence of hepatitis C virus antibodies and hepatitis C virus-RNA in an urban population.

Several studies had been carried out on anti-hepatitis C virus (HCV) prevalence in populations with blood exposure risks and in blood donors. New tests are now available which allow the investigation to extend to other parameters such as antibody type and HCV-RNA. In this study the prevalence of anti-HCV c100-3 and the associated epidemiological, clinical, and virological markers were evaluated in subjects from an urban population located in central Italy. In positive cases the time persistence of HCV-RNA and anti-HCV antibody pattern was studied. For this purpose, sera from 1,484 randomly sampled individuals, aged 30-69 years, collected in 1985 and stored at -80 degrees C were retrospectively tested. The prevalence was 0.87% (i.e., 13 anti-HCV c100-3 positive cases). A significant association was observed with raised alanine transaminase (ALT) levels (P less than 0.001). Paired serum samples from 11 out of the 13 subjects collected in 1985 and 1991 were tested by nested polymerase chain reaction (PCR) using primers from the 5' non-coding region and by 4-RIBA. Concordant RIBA patterns between 1985 and 1991 were observed in the majority of positive paired sera (7/9) as well as for HCV-RNA (6/9). HCV-RNA was present in sera simultaneously positive to both types of antibody or to anti-c100-3 or anti-c22 alone. A wide spectrum of viral and antibody patterns in anti-HCV c100-3 positive sera was observed in this urban population and persisted for at least 6 years.

Adult↗
PubMed1991

Effects of blood transfusion on the immune responsiveness and survival of cancer patients: a prospective study.

To evaluate whether blood transfusion exerts an adverse influence on cancer evolution, a prospective clinical and immunologic investigation was carried out on 58 surgical patients with gastric or colorectal adenocarcinoma. None had had previous transfusion; 35 received perioperative transfusion. Among preoperative variables, only red cell count and hemoglobin concentration were significantly reduced in the patients transfused at operation. Other clinical characteristics and immunologic functions (except interferon-gamma release) did not differ significantly from those of untransfused patients. The survival rate of transfused patients, although shorter, was not significantly different from that of untransfused patients. Immunologic tests done after surgery on 30 patients (17 transfused and 13 untransfused) did not show significant differences in the two groups. Significant increases in interleukin-2-stimulated production and immunoglobulin M synthesis were observed in transfused patients after surgery. Patients transfused perioperatively with more than 3 units of blood had some evidence of decreased immune function, but differences were not significant. While shorter survival and some immunologic changes may correlate with the number of transfusions, more patients must be studied to determine whether this relationship will be confirmed.

Blood Transfusion↗
PubMed1990

Investigation on the humoral immune response in patients with gastro-intestinal cancer.

The humoral immune reactivity was studied in patients affected by gastro-intestinal cancer. The number of peripheral B lymphocytes, the concentration of serum immunoglobulins (Ig) and of C3 complement factor and the frequency of circulating immuno complexes (CIC) did not significantly differ between patients and age-matched controls, while the C4 factor level was significantly increased. The frequency of serum monoclonal components (M-components) was higher in the patients than in the elderly subjects. Moreover the results concerning the "in vitro" functional response of patient B lymphocytes showed a significant decrease of the proliferative responses to Staphylococcus Aureus Cowan I (SAC) and a significant increase of the IgG and IgM synthesis by peripheral blood mononuclear cells (PBMC) in unstimulated and pokeweed mitogen (PWM) stimulated cultures. The meaning of these results, taken together with those reported by others, is discussed.

Adult↗
PubMed1987

Effects of the allogeneic stimulation on B cell function in thalassaemic polytransfused patients.

The immunological abnormalities of polytransfused patients affected by beta-thalassaemia major have been investigated in relation to B cell function. The spontaneous in vitro production of Ig by patient peripheral mononuclear cells was not modified, while the pokeweed mitogen induced IgM synthesis was significantly reduced. However, by comparing the splenectomized and non-splenectomized patients, this alteration proved to be present only in the splenectomized group. The proliferation of patient peripheral B cells in vitro stimulated with B cell growth factor alone was not significantly enhanced in respect to the controls. These results indicate that in vivo activation state of patient B cells is not different from that of the controls. The stimulation of peripheral B cell with anti-mu or anti-alpha antibodies and anti-mu and anti-alpha antibodies plus B cells growth factor induced a significant increase in proliferative responses of B cells from the splenectomized patients. Taken together, these findings suggest that circulating B cells of thalassaemic polytransfused patients are not hyperactivated. The splenectomy can account for the immunological changes observed in our thalassaemic sample as compared to control group.

Adolescent↗
PubMed1983

[Changes in ocular tone, pH, ascorbic acid and lactic acid concentration in the aqueous humor of rabbits treated with aceclidine].

The Authors state the results of their research on the modification of the aqueous humor caused by the instillation of the Clonidina to the concentrations of 0,I25% in a group of ten rabbits. The results of these studies illustrate the variations of pH, the ocular tone, the concentration of lactic and ascorbic acid. In all the rabbits examined Clonidina was instillated in the RE while in the LE distilled water was instillated for the control. For two hours from the beginning of the experiment, every IO minutes measurements of the ocular tone in both eyes were taken. At the end of the two hours a sample of aqueous humor was taken from the RE and LE; It was found that: I) The drugs produced a very quick and prolonged decrease of the ocular tone. 2) There are no significant variations in the pH or in the concentration of lactic acid. 3) There was a notable reduction of the concentration of ascorbic acid.

Animals↗
PubMed1983

[Changes in ocular tonus, pH and concentration of ascorbic acid and lactic acid in the aqueous humor of rabbits treated with epinephrine].

The authors state the results of their research on the modification of the aqueous humor caused by the instillation of the Epinephrine in a group of ten rabbits. The results of these studies illustrate the variations of pH, the ocular tone, the concentration of lactic and ascorbic acid. In all the rabbits examined Epinephrine was instillated in the RE while in the LE distilled water was instillated for the control. For two hours from the beginning of the experiment, every 10 minutes measurements of the ocular tone in both eyes were taken. At the end of the two hours a sample of aqueous humor was taken from the RE and LE; It was found that: 1) The drugs produced a vary quick and prolonged decrease of the ocular tone. 2) There are no significant variations in the pH or in the concentration of lactic acid. 3) There was a notable reduction of the concentration of ascorbic acid.

Animals↗
PubMed1983

[Changes in ocular tonus, pH and concentration of ascorbic acid and lactic acid in the aqueous humor of rabbits treated with clonidine].

The authors state the results of their research on the modification of the aqueous humor caused by the instillation of the Clonidine in a group of ten rabbits. The results of these studies illustrate the variations of pH, the ocular tone, the concentration of lactic and ascorbic acid. In all the rabbits examined was instillated Clonidine for one hour in RE while in LE distilled water was instilled for the control. For two hours from the beginning of the experiment every 10 minutes measurements of the ocular tone in both eyes were taken. At the end of two hours a sample of aqueous humor was taken from LE and RE. It was found that: 1) The drugs produced a vary quick and prolonged decrease of the ocular tone. 2) There are no significant variations in the pH or in the concentration of lactic acid. 3) There was a notable reduction of the concentration of ascorbic acid.

Animals↗
PubMed1983

Synthesis, biological data and correlation analysis in a set of analgesic drugs.

A set of ortho-disubstituted benzene derivatives (2-X--C6H4NH--Y) designed as analgesics has been studied. Some physicochemical properties which are potentially correlated with the considered pharmacological activities are determined. Quantitative structure-activity relationships (QSAR) show that the analgesic potency (writhing test) is a function of the hydrophobic-lipophilic parameters associated with the structures under study. Since the derivatives are inactive or very poor inhibitors of prostaglandin biosynthesis, the appropriate modulation of substituents may maximize the differentiation between anti-nociceptive and analgesic activity.

Acetates↗
PubMed1983

Immune profile alterations in thalassaemic patients.

Aspects of the humoral and cellular immune response have been studied in polytransfused patients with beta-thalassaemia major. Serum immunoglobulins (G, A, M) levels were significantly higher than in controls; reduced C4 serum level and high incidence of circulating immune complexes and anti-nuclear autoantibodies were found in the majority of patients. Marked increases were also observed in absolute and relative numbers of lymphocytes and their subpopulations. Such results suggested that the allogenic stimulation, by frequent transfusion, is the mainly responsible of the immunological alterations observed in these patients.

Adolescent↗
PubMed1981

[Detection of circulating immune complexes with the polyethylene glycol precipitation test: advantages and limitations of the method].

The precipitation test with 3.5% PEG has been used to reveal the presence of circulating immuno complexes (IC) in a sample of 130 blood donors. The asymmetry in the O.D. distribution has been corrected by the square root transformation. The positivity threshold has been fixed at the superior extreme of the 95% fiducial interval relative to the transformed data of the control sample, namely at 0.125 O.D.280nm. The correlation between O.D. values obtained with PEG-test and serum concentration of IgG, IgA, IgM, C3 has been studied in 50 of 130 blood donors, 53 patients with gastro-intestinal neoplasm, 73 patients with different forms of the rheumatic disease and 17 patients with cryoglobulinaemia. No significant correlation has been found in normal subjects. Instead, a positive correlation could be demonstrated between O.D. values and IgG concentration both in neoplastic, rheumatic and cryoglobulinemic patients, between O.D. values and IgM concentration in rheumatic patients only; a negative correlation has been found in rheumatic patients with regard to C4. The analytical results are, finally, discusses in relation to the reliability of the method as routine test for the detection of circulating IC.

Antigen-Antibody Complex↗