Search PubMed⌕ Search

Biomedical subjects

G P Pescarmona

Publications and source records attributed to G P Pescarmona.

At least 19 recordsLinked to original sources
PubMed2005

Glutathione levels in patients with erectile dysfunction, with or without diabetes mellitus.

The reduced form of glutathione (GSH) is the most important cell antioxidant and is also an essential cofactor for nitric oxide (NO) synthase that synthesizes NO from l-arginine. Reduced levels of GSH, due both to a hyperglycaemia-induced increase of free radical production and to a decrease of NADPH levels [like in diabetes mellitus (DM)], can hamper the endothelial cell functions. This condition may play an important role in the aetiology of some clinical signs, like erectile dysfunction (ED). The aim of this study was to test the hypothesis that GSH concentration is reduced in patients with ED and type 2 diabetes mellitus. We studied 111 male patients with ED: 64 with diabetes (ED/DM) and 47 without diabetes (ED/wDM); 20 patients with diabetes but without ED (DM) and 26 male normal subjects as a control group (C). The GSH red blood cell concentration was significantly lower in ED than in C (X +/- SD; 1782.12 +/- 518.02 vs. 2269.20 +/- 231.56 mumol/L, p < 0.001). In particular, GSH was significantly reduced in ED/DM vs. ED/wDM (1670.74 +/- 437.68 vs. 1930.63 +/- 581.01 micromol/L, p < 0.01). In DM, GSH was significantly lower than in C and significantly higher than in ED/DM (2084.20 +/- 118.14 vs. 2269.20 +/- 231.56 and vs. 1670.74 +/- 437.68 micromol/L, p < 0.002 and p < 0.001 respectively). GSH showed a negative correlation with fasting glucose concentrations (r = -0.34, p < 0.01) and with the duration of DM (r = -0.25, p < 0.05). A GSH depletion can lead to a reduction of NO synthesis, thus impairing vasodilation in the corpora cavernosa.

Body Mass Index↗
PubMed2002

Platelet cyclic guanosine monophosphate production during menstrual cycle in healthy women.

UNLABELLED: The incidence of cardiovascular disease among women during their reproductive years is considerably less than in men and this difference decreases after menopause. Since in cultured endothelial cells and in platelets E2 increases nitric oxide (NO) production, it is possible that their cardioprotective effect may be mediated by NO. The aim of this study was to evaluate platelet cyclic guanosine monophosphate (cGMP), as a marker of NO production, during menstrual cycle. Fifteen women aged 26-40 yr were studied to evaluate: LH, FSH, E2, P and cGMP on the 5th follicular and 22nd luteal day of the cycle and during the ovulatory period. Platelet cGMP was evaluated in basal condition (3-isobuthyl 1-methylxanthine-IBMX) and with ionomycine (IONO) and sodium nitroprusside (SNP). RESULTS: LH, FSH, E2 and P demonstrated the typical patterns of ovulatory cycle. During follicular and luteal IBMX, SNP and IONO phase were homogeneous while they increased during the ovulatory period. A correlation between IBMX cGMP and E2 (p<0.002, rs=0.456) was found. In conclusion the data show an increase in platelet cGMP during the ovulatory period and a correlation between E2 and cGMP suggesting that E2 modulates NO production. The cardioprotective effect of E2 may be, at least in part, mediated by the increase in NO production.

1-Methyl-3-isobutylxanthine↗
PubMed2002

Serum citrate levels, haptoglobin haplotypes and transferrin receptor (CD71) in patients with HIV-1 infection.

BACKGROUND: The progression of HIV-1 infection towards its more advanced stages is accompanied by changes in iron metabolism and increased body iron stores. PATIENTS AND METHODS: Given the ability of HIV to alter iron metabolism, we studied the principal (transferrin system) and alternative (citrate system) iron pathways in a group of 65 HIV-infected patients (symptomatic stage B1-B3) and in a group of 36 healthy seronegative individuals. We determined serum citrate levels, haptoglobin (Hp) haplotypes, expression of transferrin receptor (CD71) on cell lines infected with HIV-1 as well as iron markers including blood iron, transferrin and ferritin. RESULTS: Our data showed decreased serum citrate levels in the HIV-infected patients compared to controls (92.9 +/- 22.4 microM/l vs 126.2 +/- 29.2 microM/L; p < 0.01). In particular, the serum citrate levels negatively correlated with HIV-1 RNA copy number (mean: 2.53 +/- 1.88 x 10(5)/ml, r(s) = 0.70, p < 0.01) and positively correlated with CD4+ T-lymphocyte count (mean: 241 +/- 168/ml, r(s) = 0.64, p > 0.05). Accordingly, blood iron, transferrin and red cell concentrations were lower in HIV-infected patients compared to the controls, whereas serum ferritin levels were higher in HIV-infected patients. Moreover, the Hp haplotype distribution showed significant differences only in the group of HIV-infected patients (p = 0.02; chi2 test). CONCLUSION: Our results show that iron metabolism is altered in patients with HIV-1 infection. The alternative pathway (citrate system) is particularly affected, since when citrate levels are low, both aconitase activity and HIV-1 replication need iron.

Adult↗
PubMed2001

Administration of glutathione in patients with type 2 diabetes mellitus increases the platelet constitutive nitric oxide synthase activity and reduces PAI-1.

Several studies suggest that nitric oxide (NO) production is impaired in diabetes mellitus. Reduced levels of NO could contribute to cardiovascular mortality. Furthermore, NO synthesis is impaired in glutathione (GSH)-depleted human umbilical vein endothelial cells and GSH is reduced in patients with type 2 diabetes mellitus (T2DM). We tested the hypothesis that treatment with GSH may improve platelet constitutive NO sinthase (cNOS) activity in patients with T2DM. Fifteen patients with T2DM underwent a treatment with GSH 600 mg/day i.m. for 10 days. With respect to the basal values on the 10th day of treatment, the red blood cell GSH concentration and platelets cNOS increased (1.4+/-0.1 vs 1.9+/-0.1 micromol/10(10) RBC, p<0.001 and 0.7+/-0.1 vs 2.9+/-0.2 fmol x min(-1) x 10(-9) PLTs, p<0.001, respectively) and the plasma PAI-1 levels diminished (81.4+/-3.7 vs 68.7+/-4.0 ng/ml, p<0.002). A negative correlation between the cNOS and the PAI-1 was found on the basal values. After a wash-out of 30 days the values of red blood cell GSH concentration, platelet cNOS activity and PAI-1 Ag returned to the basal levels. These data suggest that the administration of GSH, in patients with T2DM, is able to improve platelet cNOS activity together with a reduction of PAI-1.

Aged↗
PubMed2001

Serum DHEAS levels correlate with platelet cGMP in normal women.

Several studies suggest that DHEAS is a protective factor against atherosclerosis and coronary artery disease in man, but the mechanism of its biological role is unclear. Recently, it has been suggested that DHEAS can retard atherosclerosis formation through an increase in nitric oxide (NO) production by increasing E2 synthesis. The aim of the study was to evaluate the platelet cGMP concentrations (i.e. a marker of NO production) and the serum levels of DHEAS and E2 in normal females. Blood samples were taken from 51 normal women (age 42.3+/-1.9 yr, range: 22-67 yr, BMI 23.0+/-0.6 kg/m2) to evaluate platelet cGMP concentrations and serum levels of DHEAS and E2. To determine the platelet cGMP content, platelet rich plasma (PRP) was incubated at 37 C (30 min) in the presence of IBMX. The amount of platelet cGMP was measured by a cGMP (3H) assay kit. In all subjects the mean of platelet cGMP was 536.2+/-45.3 fmol/10(6) platelets and the mean of serum DHEAS and E2 was 151.4+/-13.9 microg/dl and 34.7+/-6.1 pg/ml, respectively. In all subjects DHEAS positively correlates with cGMP (p<0.001, r=0.513) and with E2 (p<0.001, r=0.650); furthermore E2 positively correlates with cGMP (p<0.001, r=0.663). In conclusion our data support the hypothesis that DHEAS exerts its antiatherogenic effect by increasing the NO production directly and/or by increasing the E2 synthesis.

Adult↗
PubMed2000

Local interaction simulation approach for the response of the vascular system to metabolic changes of cell behavior.

The self-regulatory interactions between cells and the vascular system are mediated by signals propagating at a finite speed. In order to build up a physical model of these processes, several features, such as storing of internal energy, nonclassical nonlinear behavior, and delay and threshold effects, have to be taken into account. Considering cells as particles in different metabolic states according to their internal energy, we have developed a model based on the local interaction simulation approach. Several numerical results, in qualitative agreement with biological observations, illustrate the applicability of the model and the method to implement it.

Animals↗
PubMed2000

A physical-based model for the simulation of neoplastic growth and metastasis.

BACKGROUND AND OBJECTIVES: It is possible to formulate models capable of reproducing the main details of the physical processes involved in the evolution of biological systems. The complexity of the problem requires to begin with a simple and universal model for the description of the cellular growth, to be adapted successively to the local conditions found in clinically observed neoplastic growths. METHODS: A model based on the Local Interaction Simulation Approach (LISA) has been formulated for the simulation of growth, diffusion, and metastasis of neoplasms. The vascularization is described by a blood vessel located on one edge of the specimen in which a constant and homogeneous flow is assumed. A nutrient density is defined to mimic the blood flow within the tissue. RESULTS: Photograms taken at proper times may identify the main characteristics of the tumor evolution and describe its volume variations in a transversal section. Furthermore, it is possible to monitor constantly the volume of the neoplasm and of the necrotic tissue as a function of time, as well as the portion of cells that have migrated in the blood vessel. CONCLUSIONS: In spite of strong simplifying assumptions, the model presents good qualitative agreement with clinical data, which may be further improved by more detailed information about cancer cells properties or local vascular system patterns.

Animals↗
PubMed2000

Analysis of a "phase transition" from tumor growth to latency.

A mathematical model, based on the local interaction simulation approach, is developed in order to allow simulations of the spatiotemporal evolution of neoplasies. The model consists of a set of rules, which govern the interaction of cancerous cells among themselves and in competition with other cell populations for the acquisition of essential nutrients. As a result of small variations in the basic parameters, it leads to four different outcomes: indefinite growth, metastasis, latency, and complete regression. In the present contribution a detailed analysis of the dormant phase is carried on and the critical parameters for the transition to other phases are computed. Interesting chaotic behaviors can also be observed, with different attractors in the parameters space. Interest in the latency phase has been aroused by therapeutical strategies aiming to reduce a growing tumor to dormancy. The effect of such strategies may be simulated with our approach.

Cell Division↗
PubMed1999

Effect of Aspergillus terreus mycotoxins on nitric oxide synthase activity in human erythroid K-562 cells.

Because several stimuli of microbial origin enhance the activity of nitric oxide synthase (NOS) in human cells of the myeloid lineage, we decided to investigate whether cellular damage induced by Aspergillus terreus mycotoxins could be associated with an increase in NOS activity. A pool of mycotoxins rather than individual toxins was tested so that the natural conditions could be mimicked. In the present study, we report that a crude extract of A. terreus induces cellular damage and increases NOS activity in K-562 cells, an erythroleukaemic cell line in which NOS is particularly active. The specificity of this association was further investigated by using NOS inhibitors and by comparing, in the same cellular model, the effects of the extract with the activity of other microbial toxins of a defined mechanism of action. Canavanine, an inhibitor of NOS, significantly reduced cell death in the presence of the extract, suggesting that cellular damage, induced by the mycotoxins of A. terreus is at least in part mediated by NOS activity. Moreover, Escherichia coli lipopolysaccharide (LPS), known to be a potent NOS inducer, increased NOS activity in our experimental model as well. In contrast, Bordetella pertussis toxin did not show any effect on NOS activity. The results of this study suggest that NOS may be involved in mycotoxicoses.

Aspergillosis↗
PubMed1999

Modulation of surface transferrin receptors in lymphoid cells de novo infected with human immunodeficiency virus type-1.

To investigate whether transferrin receptor (CD71) expression is affected by acute HIV-1 infection, three different lymphoid cell lines (MT-4, SUPT-1, H9) were infected with HIV-1 and tested for surface CD71 expression after different incubation periods depending on cell survival after infection. We found that expression of surface CD71 was lower in cells infected with HIV-1 than in uninfected controls: the timing and extent of this down-modulation depended apparently on the different susceptibility of the cell lines to HIV-1 infection and cytopathogenicity. Citrate, a molecule capable of chelating iron, dose-dependently prevented down-modulation of surface CD71 in HIV-1 infected cells as well as viral cytopathic effects. We conclude that (i) expression of surface transferrin receptors is down-modulated by acute HIV-1 infection in T lymphoid cells, that (ii) this cell phenotypic modulation is associated with the cytopathic effects of the virus, and that (iii) these phenomena are modulated by iron chelation. These results support the view that iron metabolism may be an important area for interaction between HIV-1 and human cells.

ADP-ribosyl Cyclase↗
PubMed1999

Iron metabolism and HIV infection: reciprocal interactions with potentially harmful consequences?

Humans with advanced human immunodeficiency virus (HIV) infection present some evidence suggestive of iron accumulation. Ferritin concentrations increase with HIV disease progression, and iron accumulates in several tissues. Iron excess may exert negative effects in individuals with HIV. Indeed, iron accumulation seems to be associated with shorter survival, and a number of investigations point to an iron-mediated oxidative stress in subjects with HIV infection. The observations on humans infected with HIV are in part supported by in-vitro findings. Indeed, in-vitro HIV infection is associated with changes in iron metabolism, and an iron-mediated oxidative stress is likely to contribute to viral cytopathogenicity. Furthermore, it is interesting to point out that the interaction between iron and HIV may be reciprocal, since viruses with a life-cycle involving a DNA phase require chelatable iron for optimum replication. This combined evidence suggests that iron metabolism is an important area for virus/host interaction. These observations may be relevant to both laboratory monitoring and clinical treatment of individuals with HIV.

Animals↗
PubMed1999

Non-linear model of cancer growth and metastasis: a limiting nutrient as a major determinant of tumor shape and diffusion.

A new approach for modelling the spatio-temporal evolution of tumors is presented. To test its validity, a very basic model is considered, which, in spite of its simplicity, is capable of generating a multiplicity of morphologies and growth and migration rates. From an in-vivo scenario of basic life processes, cancer cell proliferation is described as a competition for basic nutrients. The chosen mathematical treatment and simulation techniques permit a direct implementation of the local nonlinear couplings existing between the various cell populations and the free and bound nutrient concentration. A discussion of the results and proposed improvements and applications of the model is also presented.

Cell Division↗
PubMed1998

The biochemistry of gene therapy for AIDS.

Gene therapy has enormous potential and could in the near future involve the clinical biochemist in monitoring its efficacy. The involvement of clinical biochemists in this field could be not only in evaluating the impact of a gene-based strategy on disease progression, but also in measuring the expression of the products of therapeutic genes in treated individuals. Indeed, gene therapy presents new possibilities for the treatment of many diseases and, in particular, merits consideration in the treatment of a fatal disease like AIDS. The aim of this paper is to review the biochemical basis and clinical relevance of the gene therapy approaches directed towards the inhibition of human immunodeficiency virus type-1. We discuss the goals which have been achieved, the problems which have occurred and the efforts that are being made to solve them. In this regard, particular attention is paid to new strategies targeting 'therapeutic' enzymes to human immunodeficiency virus type-1 nucleic acids.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Calcium blood level modulates endogenous nitric oxide action: effects of parathroidectomy in patients with hyperparathyroidism.

UNLABELLED: Platelet cyclic guanosine monophosphate (cGMP) is produced by soluble guanylate cyclase (sGC), the activity of which is modulated by the activity of nitric oxide (NO) constitutive synthase (cNOS) which, in turn, is activated by a calcium/calmodulin complex. In primary hyperparathyroidism (H-PTH) an increase in platelet free calcium levels is present. In this study we evaluate the platelet cGMP levels, as an expression of NO production, in the presence of 3-isobutyl-1-methylxanthine (IBMX) alone (IBMXcGMP) and after stimulation by ionomycine (IONO; IONOcGMP) and sodium nitroprusside (SNP; SNPcGMP), in eight subjects affected by H-PTH before and after removal of adenoma. Platelet cGMP levels were also measured in seven normal subjects. IBMXcGMP and IONOcGMP were elevated in H-PTH patients compared with normal subjects (1.9 +/- 0.3 vs 0.8 +/- 0.2 fmol/10(6) platelets and 2.7 +/- 0.4 vs 1.4 +/- 0.3; P < 0.02 and P < 0.05 respectively) but SNPcGMP was unaffected (3.9 +/- 0.6 vs 2.5 +/- 0.5). After parathyroidectomy, blood levels of intact parathyroid hormone (i-PTH), total calcium (t-Ca), IBMXcGMP and IONOcGMP all decreased (177.5 +/- 23.9 vs 45.0 +/- 8.8 pg/ml, P < 0.005; 6.5 +/- 0.5 vs 4.6 +/- 0.1 mEq/1, P < 0.005; 1.9 +/- 0.3 vs 0.8 +/- 0.2, P < 0.005; 2.7 +/- 0.4 vs 1.8 +/ 0.3, P < 0.05 respectively), while SNPcGMP was not modified (3.9 +/- 0.6 vs 4.3 +/- 0.9). t-Ca and i-PTH were directly correlated with IBMXcGMP (P < 0.02, rs = 0.613; P < 0.02, rs = 0.576 respectively) and i-PTH was also correlated with t-Ca (P < 0.001), rs = 0.840). IN CONCLUSION: (1) levels of IBMXcGMP and IONOcGMP are high in subjects with H-PTH; (2) after surgery both IBMXcGMP and IONOcGMP decrease to normal values. As IBMXcGMP expresses basal cGMP and IONOcGMP expresses the cGMP after cNOS stimulation, it can be speculated that the increase in NO production could be a mechanism to downregulate the vasoconstriction which may be caused by the high calcium levels in smooth muscle cells. After surgery, together with the normalization of calcium levels, NO production also returned to normal values.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Activation of endothelial guanylate cyclase inhibits cellular reactivity.

The study shows that endothelial cells from human umbilical veins have a soluble guanylate cyclase which can be activated by sodium nitroprusside (SNP), SIN-1 (3-morpholinosydnonimine) and S35b (4-methyl-3-phenylsulfonylfuroxan). Cells which were pretreated with these compounds showed an inhibition of thrombin-induced arachidonic acid release, PGI2 formation, PAF synthesis and PMNL adhesion. Endothelial guanylate cyclase can also be activated by nitric oxide (NO) which is generated in endothelial cells upon stimulation with thrombin or ionomycin. It is suggested that endogenously produced NO might control cell activation and endothelial function through a cGMP-dependent mechanism.

Arachidonic Acid↗
PubMed1993

Kinetic characterization of Na+/H+ antiport of Plasmodium falciparum membrane.

Intraerythrocytic malaria parasites produce vast amounts of lactic acid through glycolysis. While the egress of lactate is very rapid, the mode of extrusion of H+ is not known. The possible involvement of a Na+/H+ antiport in the extrusion of protons across the plasma membrane of Plasmodium falciparum has been investigated by using the fluorescent pH probe 6-carboxyfluorescein. The resting cytosolic pH was 7.27 +/- 0.1 in ring stage parasites and 7.31 +/- 0.12 in trophozoites. Spontaneous acidification of parasite cytosol was observed in Na(+)-free medium and realkalinization occurred upon addition of Na+ to the medium in a concentration-dependent manner, with no apparent saturation. The rate of H(+)-efflux at the ring stage was higher than that at the trophozoite stage due to the larger surface/volume ratio of the young parasite stage. Na(+)-dependent H(+)-efflux was: 1) inhibited by the Na+/H+ inhibitors amiloride and 5-(N-ethyl-N-isopropyl) amiloride (EIPA), though at relatively high concentrations; 2) augmented with rising pH6 (pHi = 6.2, [Na+]o = 30 mM); and 3) decreased with increasing pHi (pHo = 7.4; [Na+]o = 30 mM). The pHi and the pHo dependencies of H(+)-efflux were almost identical at all parasite stages. Only at pHi > 7.6 efflux was totally obliterated. The target of this inhibitory effect is probably other than the antiport. Results indicate that H(+)-egress is mediated by a Na+/H+ antiport which is regulated by host and parasite pH and by the host cytosol sodium concentration. The proton transport capacity of the antiport can easily cope with all the protons of lactic acid produced by parasite's glycolysis.

Amiloride↗
PubMed1993

Proliferative and migratory responses of murine microvascular endothelial cells to granulocyte-colony-stimulating factor.

Microvascular murine endothelial cells lines transformed by middle T oncogene of polyoma virus maintain the biological characteristics of nontransformed microvascular endothelial cells (EC). By using cell lines originated from different anatomical districts (thymus, brain, heart, and skin), we demonstrated that murine granulocyte-colony-stimulating factor (G-CSF) induces proliferation of murine microvascular endothelial cells at nanomolar concentrations without any cooperation with fetal calf serum. The proliferative effect on murine cells is less than that elicited by epidermal growth factor (EGF), used as standard for this function. G-CSF also promotes the migration of tEnd.1 endothelial cell line assayed by Boyden chamber technique. The analysis of transcript for G-CSF receptor (G-CSFR) by Northern blot hybridization and by reverse-transcriptase polymerase chain reaction (RT-PCR) shows that these cell lines have specific mRNA, with the size of that present in myeloid cells. These results indicate that G-CSF operates in the microvascular endothelial cells by a mechanism related to the presence of a specific receptor.

Animals↗