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Biomedical subjects

G Guidi

Publications and source records attributed to G Guidi.

At least 19 recordsLinked to original sources
PubMed1992

Selenium and glutathione peroxidase variations induced by polyunsaturated fatty acids oral supplementation in humans.

Serum and erythrocyte selenium, erythrocyte and platelet glutathione-peroxidase (GSH-Px) activities, and erythrocyte reduced glutathione (GSH) content were measured in 25 healthy adult individuals before and after daily supplementation with 20 ml of fish oil for 10 weeks. Serum-Se decreased from 0.83 +/- 0.01 mumol/l to 0.75 +/- 0.02 mumol/l (mean +/- S.E.M.) (P less than 0.01); erythrocyte-Se decreased from 4.39 +/- 0.17 nmol/g hemoglobin (Hb) to 2.83 +/- 0.15 nmol/g (P less than 0.001). GSH-Px activities increased both in erythrocytes (6.93 +/- 0.24 iu/g vs 8.18 +/- 0.27 iu/g Hb, P less than 0.01) and in platelets (69.2 +/- 2.8 iu/g vs 90.9 +/- 3.6 iu/g protein, P less than 0.001). The concentration of GSH in erythrocytes fell from 9.56 +/- 0.29 mumol/g Hb to 5.90 +/- 0.30 mumol/g Hb (P less than 0.001). The effects on plasma lipids were evident only for triglycerides (before 1.96 +/- 0.16 mmol/l, after 1.75 +/- 0.14 mmol/l, P less than 0.001). We hypothesise the enrichment of erythrocyte and platelet membranes with polyunsaturated fatty acids (PUFAs), following fish oil intake, can generate increased amounts of lipid peroxides and thus allosterically activate GSH-Px: with time this is harmful for the integrity of the enzyme molecule and Se release may result. We suggest that the Se status of individuals given PUFAs is assessed before and during intake; Se supplements should only be given when serum and/or erythrocyte Se are reduced.

Administration, Oral↗
PubMed1992

Behavioral effects of L-alpha-glycerylphosphorylcholine: influence on cognitive mechanisms in the rat.

The phosphorylcholine precursor, L-alpha-glycerylphosphorylcholine (alpha-GPC), was injected at the dose of 100 mg/kg/day for 20 days to aged male rats of the Sprague-Dawley strain, 24 months old, showing a deficit of learning and memory capacity. The drug was also administered to rats with amnesia induced pharmacologically with bilateral injections of kainic acid into the nucleus basalis magnocellularis (NBM). Learning and memory capacity of the animals, studied with tests of active and passive avoidance behavior, was improved after treatment with alpha-GPC in all experimental groups. These results indicate that this drug affects cognitive mechanisms in the rat through an involvement of central neurotransmission.

Animals↗
PubMed1992

Prevalence of feline immunodeficiency virus and other retroviral infections in sick cats in Italy.

Two hundred and seventy-seven sick pet cats living in Italy were tested for antibodies to feline immunodeficiency virus (FIV) and for feline leukemia virus (FeLV) antigen. Overall, 24% of the cats resulted positive for anti-FIV antibody and 18% for FeLV antigen. FIV was isolated from the peripheral mononuclear blood cells of ten out of 15 seropositive cats examined and from one out of eight saliva samples. No FIV isolations were obtained from six serum samples cultured. Feline syncytium forming virus (FeSFV) could be isolated from blood and/or saliva in ten out of 11 FIV seropositive cats examined, in six out of nine FeLV antigen positive cats, in two cats found positive for both infection markers, and in three out of 11 cats negative for both markers. Thus, the probability of isolating FeSFV was enhanced by infection with other exogenous retroviruses.

Animals↗
PubMed1991

Increased expression of C3b and C3bi receptors on human neutrophils and monocytes induced by a glycoprotein extract from Klebsiella pneumoniae (RU41740).

RU41740 is a glycoprotein extract from Klebsiella pneumoniae with immunomodulating properties under different experimental conditions. In particular the compound is able to stimulate several functions of human phagocytes in vitro and ex vivo. Using monoclonal antibodies and flow cytometry, in this work we assessed the effect of RU41740 on surface expression of receptors for C3b (CR1) and C3bi (CR3) in human phagocytic cells in vitro. The incubation of whole blood with varying RU41740 concentrations led to a dose-dependent increase in surface expression of CR1 and CR3 on both neutrophils and monocytes when compared with control samples incubated in buffer alone. The maximal drug-induced enhancement of complement receptors was: 291% +/- 13.4% for CR1 and 265% +/- 8.5% for CR3 in neutrophils; 117% +/- 4.5% for CR1 and 98% +/- 4.1% for CR3 in monocytes. These peak effects were observed using RU41740 at a final concentration of 10 micrograms/ml and were similar to those induced by optimal concentrations of the activating compound N-formyl-methionyl-leucyl-phenylalanine (10(-7)M). Polymyxin B did not modify the RU41740-induced enhancement of CR1 and CR3 expression on phagocytes, suggesting no role for endotoxin in this activity. These results define, at least in part, the mechanism of action of RU41740 on human phagocytes in vitro and could be relevant to in vivo events during RU41740 treatment.

Adjuvants, Immunologic↗
PubMed1991

Effect of a new peptidyl-hypoxanthine derivative on natural killer cells and antitumor activity.

A new immunomodifier, [omega-(hypoxanthin-9-yl) pentoxy-carbonyl-leucyl-methionine] (RM06), was synthesized and its effect was evaluated on the activity of Natural Killer (NK) cells. Results indicate that RM06 is able to boost the NK activity of normal mice as well as to augment the regeneration of NK activity of lethally irradiated mice transplanted with syngeneic bone marrow (BM). This later effect also correlated with a significant increase in anti-tumor activity as evaluated by the resistance to metastasis in mice injected with syngeneic melanoma cells. These data indicate that RM06 is able to modulate the NK cell activity as well as the antitumor resistance.

Adjuvants, Immunologic↗
PubMed1990

Modulation of mediator release from human basophils and pulmonary mast cells and macrophages by auranofin.

Auranofin, a new orally absorbable gold compound, inhibits IgE-(anti-IgE) and non-IgE-mediated (f-met-peptide and the Ca2+ ionophore A23187) histamine release from human basophils. Auranofin inhibits the release of histamine induced by phorbol myristate (TPA) and bryostatin 1 both in the presence and absence of extracellular Ca2+. Increasing the Ca2+ concentrations in the extracellular medium does not reduce the inhibitory effect of auranofin on anti-IgE- or A23187-induced secretion. Auranofin inhibits the de novo synthesis of sulfidopeptide leukotriene C4 (LTC4) induced by anti-IgE from basophils and mast cells purified from human lung. However, in both systems auranofin has a significantly greater inhibitory effect on LTC4 release than on histamine secretion. Finally, auranofin induces a concentration-dependent inhibition of A23187-induced leukotrine B4 (LTB4) release from purified human lung macrophages. These data suggest that auranofin modulates the release of preformed (histamine) and de novo synthesized (LTC4 and LTB4) chemical mediators from human inflammatory cells isolated from peripheral blood and human lung tissues.

Auranofin↗
PubMed1990

Pharmacokinetics of the total triterpenic fraction of Centella asiatica after single and multiple administrations to healthy volunteers. A new assay for asiatic acid.

A new HPLC assay method was used to investigate the pharmacokinetics of asiatic acid after oral administration of the total triterpenic fraction of Centella asiatica in single doses (30 or 60 mg) and after a 7-day treatment (30 or 60 mg twice daily). Twelve healthy volunteers received each treatment following a randomized cross-over design with trials separated by a 3-week interval. The time of peak plasma concentration was not affected by dosage difference or by treatment scheme. Differences in peak plasma concentration and area under the concentration vs. time curve from 0 to 24 h (AUC0-24) calculated after 30 or 60 mg administration (single dose) were accounted for by the different dose regimen. However, after chronic treatment with both 30 and 60 mg, peak plasma concentrations, AUC0-24 and half-life were significantly higher than those observed after the corresponding single dose administration. This phenomenon could be explained by a metabolic interaction between asiatic acid and asiaticoside, which is transformed into asiatic acid in vivo.

Administration, Oral↗
PubMed1990

Improvement of capillary permeability in patients with venous hypertension after treatment with TTFCA.

The VSC (vacuum suction chamber) device, a new system to evaluate local capillary permeability, was used with laser Doppler flowmetry to study variations of permeability and of the microcirculation in 10 normal subjects; in 22 patients with moderate, superficial venous hypertension; and in 12 patients with postphlebitic limbs and severe venous hypertension. All these patients had distal (ankle and foot edema) in the evening. After a first assessment these subjects were studied again after two weeks without treatment and after two weeks' treatment with total triterpenic fraction of centella asiatica (TTFCA), tablets, 60 mg, tid. The VSC produces a wheal on the skin of the perimalleolar region that disappears (in average) in less than sixty minutes in normal subjects. The disappearance time (DT) is greater in conditions of increased capillary filtration and permeability. The three groups of subjects (normal and those with superficial and severe venous hypertension) had significantly different, increasing disappearance time of the wheals at the first observation. There were no significant changes after two weeks' observation, but after 2 weeks' treatment with TTFCA, there was a significant decrease of DT both in limbs with superficial and with deep venous incompetence. The improvement (decrease) of the abnormally increased capillary permeability was associated with a significant improvement of the microcirculation and symptoms (studied by an analogue scale line). In conclusion this study showed a combined improvement of the microcirculation and capillary permeability after treatment with TTFCA and the possibility of using the VSC to evaluate the effects of drugs (or other treatment) on local capillary permeability in patients with venous hypertension.

Adult↗
PubMed1989

Effect of Biostim (RU 41.740) on natural killer cell generation from bone marrow precursors.

We have evaluated the possible effect of RU 41.740 (Biostim), a mixture of two glycoproteins extracted from K. pneumoniae, on the in vitro interleukin-2 (IL-2)-induced generation of NK cells from bone marrow (BM) precursors and on the in vivo reconstitution of splenic NK activity in lethally irradiated (9 Gy) and BM reconstituted mice. Our results show that RU 41.740 is able to augment the generation of NK cells when added (1-0.01 micrograms/ml) to normal or 5-fluorouracil-resistant BM, cultured in the presence of recombinant IL-2. Also, in vivo treatment of lethally irradiated mice, transplanted with syngeneic BM cells, with RU 41.740 (1-0.1 mg/kg i.v.) from day 0 through day 4 after BM graft, resulted in a significant augmentation of NK activity reconstitution.

Animals↗
PubMed1989

Clinical evaluation of a new anti-aliasing technique for ultrasound pulsed Doppler analysis.

Clinical evaluation of a new method of Doppler spectral analysis is discussed in this paper. According to this method, which basically involves a proper reformatting of the data provided by a conventional spectrum analyser, the frequency range usually considered in pulsed systems is considerably extended. This has been demonstrated even in extreme clinical conditions, corresponding to tight stenosis in major arteries. Details of materials and methods employed in this evaluation are included. Examples of experimental results are reported, along with a discussion about some possible applications of the new technique.

Arterial Occlusive Diseases↗
PubMed1988

Potential role of interleukin-1 as the trigger for diffuse intravascular coagulation in acute nonlymphoblastic leukemia.

Abnormalities of coagulation are common in patients with acute nonlymphoblastic leukemia, although the mechanisms involved are unclear, except in a few cases. To investigate the pathogenesis of this coagulopathy, suspensions of purified leukemic cells were prepared and tested for procoagulant activity. Neither the leukemic cells nor their supernatants directly accelerated the clotting of plasma. Since the leukemic cells did not possess direct procoagulant activity, their ability or inability to elaborate a mediator of cellular coagulant properties, interleukin-1, was studied. Leukemic cells from patients with coagulopathy elaborated interleukin-1, and addition of phytohemagglutinin increased interleukin-1 release. In contrast, no interleukin-1 was released, before or after stimulation with phytohemagglutinin, from leukemic cells from patients without coagulopathy. Leukemic cells from another group of patients with abnormalities of coagulation released interleukin-1 only after phytohemagglutinin treatment. In terms of the coagulation mechanism, interleukin-1 containing supernatants from leukemic cell cultures induced the procoagulant receptor tissue factor, a co-factor in the initiation of coagulation, on the endothelial cell surface. There was coordinate suppression of the anticoagulant endothelial cell receptor thrombomodulin, a co-factor for the antithrombotic protein C pathway. Antibody to interleukin-1 prevented these changes in cellular coagulant properties. Taken together, these changes result in a shift in the balance of endothelial cell coagulant properties to an activated state in which mechanisms promoting procoagulant reactions on the vessel surface predominate. Synthesis and release of the mediator interleukin-1 by leukemic cells thus defines a new mechanism through which malignant cells can potentially activate the coagulation mechanism.

Acute Disease↗
PubMed1988

Computer assisted laboratory diagnosis: a ten-year experience.

An automated procedure to help general practitioners in clinical diagnosis and decision making is presented. The computer-based program is conceived to process results from laboratory tests performed on outpatients, providing general practitioners with possible causes of abnormal results. When only one or two abnormal tests are observed, a series of suggestions pertinent to each abnormality is printed. When there are more abnormal test results, the program performs a more complex procedure ending with the output of some diagnostic hypotheses. Messages are also printed to focus the physician's attention to particular aspects of patient pathology that were sometimes missed or disregarded and to suggest new investigations the laboratory can perform to improve diagnostic efficiency. Moreover some advice is supplied to allow a better evaluation of particular risk conditions, as those associated with the development of coronary heart disease. The program has been recently extended with the calculation of intraindividual reference intervals. The system described has been working since 1976 and appears particularly useful when the general practitioner is faced with a number of pathological results of difficult interpretation.

Adolescent↗
PubMed1988

In vitro modulation of human monocytes functions by RU 41740 (Biostim).

The in vitro effects of RU 41740, a mixture of two glycoproteins extracted from K. pneumoniae and possessing immunomodulatory activity, on human monocyte's cytotoxic activity, migratory capacity and monokine production were investigated. Exposure to RU 41740 in nanogram concentrations was associated with rapid increases in IL-1 and TNF production and marked augmentation in the monocytes' killing of TNF-sensitive targets, whereas killing of TNF-insensitive targets required longer exposures to microgram concentrations of this drug. Using otherwise effective treatment conditions, RU 41740 did not directly affect monocyte's spontaneous and FMLP-induced migration. The possible role of mononuclear cells stimulation and increased production of effector and regulatory monokines in the immunomodulatory activity of this product is addressed.

Adjuvants, Immunologic↗
PubMed1988

In vitro and ex vivo effect of RU41740 on human polymorphonuclear leukocyte function.

We investigated the effect of RU41740, a glycoprotein extracted from Klebsiella pneumoniae and possessing immunomodulating properties, on human neutrophil functions in vitro and ex vivo. Our in vitro results showed that RU41740 increased complement- and Fc receptor-dependent phagocytosis. Moreover, the drug enhanced the oxidative metabolism (assessed by chemiluminescence) both in resting and stimulated cells; in the latter case the RU41740-induced enhancement was observed when neutrophils were stimulated with opsonized particles of N-formyl-methionyl-leucyl-phenylalanine (FMLP) but not when phorbol myristate acetate was used. Using otherwise effective experimental conditions, RU41740 did not affect spontaneous or FMLP-induced neutrophil migration. For the ex vivo experience we tested neutrophils of ten elderly subjects with a previously demonstrated phagocytic defect. These subjects were treated orally with RU41740 at a daily dose of 2 mg for 1 week during the first month, and of 1 mg for 1 week in the second month. In this population, RU41740 was able to restore the impaired phagocytic activity and to induce a significant increase of spontaneous chemiluminescence (CL); stimulated CL was also positively influenced. These effects on neutrophils provide new explanatory bases for the immunostimulatory activity of RU41740.

Adjuvants, Immunologic↗
PubMed1988

Double-blind trial RU 41740 vs. placebo: immunological and clinical effects in a group of patients with chronic bronchitis.

A double-blind trail was performed to investigate the effects of RU 41740, a glycoprotein extract from Klebsiella pneumoniae, on host defenses and its efficacy in reducing the number of exacerbation in 29 evaluable patients with chronic bronchitis, out of 36 patients who entered the study. The drug enhanced the phagocytosis indexes of both polymorphonuclear and mononuclear phagocytes. Increased candidacidal activity of monocytes was also observed. These effects, already detectable after one course of therapy and during the entire period of treatment, were no longer detectable when tested 6 months after the end of treatment. A significantly (p less than 0.05) larger number of patients in the treated group than in the placebo group had no exacerbations during drug administration (0-3 months). Moreover, patients treated with RU 41740 had significantly fewer and shorter episodes of acute exacerbation. The positive decreases in these two parameters persisted throughout the follow-up.

Adjuvants, Immunologic↗
PubMed1987

Immunomodulating activity of RU 41740: in vitro and in vivo studies on human lymphocytes.

A group of institutionalized elderly subjects, selected on the basis of their skin hypoergy and displaying different kinds of T and B lymphocyte impairments has been chosen as a model to verify the in vivo immunopotentiating activity of RU 41740 on human lymphocytes. Oral treatment with the drug was able to: restore or improve the cutaneous delayed hypersensitivity to recall antigens; significantly increase the blastigenetic response to mitogenic and submitogenic doses of PHA and PWM and improve the in vitro PWM-induced synthesis of IgG and IgM. The immunopharmacological activity of RU 41740 appeared to persist three months after the end of therapy, without any direct stimulating activity on the peripheral blood lymphocytes. The in vitro results seem to suggest that peripheral lymphocytes are not directly influenced by the drug.

Adjuvants, Immunologic↗
PubMed1986

Modulation of the release of histamine and arachidonic acid metabolites from human basophils and mast cells by auranofin.

In these experiments the effects of pharmacological concentrations of auranofin, a new absorbable gold compound, were assessed on the release of histamine and peptide leukotriene C4 (LTC4) from human basophils and lung mast cells. Auranofin, at pharmacological concentrations, inhibited in vitro histamine and LTC4 release from human basophils induced by anti-IgE. Inhibition began at about 3 X 10(-7) M and was maximum at 10(-5) M. We also evaluated the effect of auranofin on the release of histamine and LTC4 induced by anti-IgE from mast cells purified from human lung. Auranofin (3 X 10(-7) to 10(-5) M) dose-dependently inhibited the release of histamine and LTC4 from human lung mast cells. Thus pharmacological concentrations of auranofin cause dose-related inhibition of histamine release and de novo synthesis of LTC4 by human basophils and lung mast cells.

Adult↗