Biomedical subjects

E Pinto

Publications and source records attributed to E Pinto.

At least 37 records · Page 2Linked to original sources

PubMed2003

Induction of oxidative stress in the red macroalga Gracilaria tenuistipitata by pollutant metals.

Heavy metals are environmental pollutants that have the potential to induce severe stress-reactions in organisms on land as well as in the sea. We have studied effects of short term sublethal concentrations of copper (Cu2+) and cadmium (Cd2+) on the reactive oxygen metabolism of the marine red macroalga Gracilaria tenuistipitata. Additions of either 0.2 ppm Cu2+ or 1 ppm Cd2+ caused decreased growth (approximately 60%), increased oxidation of lipids and increased oxidative damage to proteins as shown by increased content of protein carbonyl groups. Together this strongly suggests an induction of oxidative stress. Cu2+ caused more oxidative damage than Cd2+. As a response to the increased oxidative stress, addition of Cu2+ induced the activities of catalase, ascorbate peroxidase, and superoxide dismutase. In contrast, Cd2+ only caused increased catalase activity. Ten-fold lower concentrations of the metals did not cause an increase in enzyme activity. Both heavy metals also increased the content of the antioxidants beta-carotene and lutein. The results show that Cd2+ and, to a larger extent, Cu2+ induce oxidative stress in short-term experiments and the seaweed responds by increasing the activity of the reactive oxygen metabolism.

Antioxidants↗

PubMed2003

Alcohol and withdrawal: from animal research to clinical issues.

The withdrawal syndrome in alcohol-dependent patients appears to be a major stressful event whose intensity increases with repetition of detoxifications according to a kindling process. Disturbances in the balance between excitatory and inhibitory neural processes are reflected in a perturbed physical state while disturbances in the balance between positive and negative reinforcements are reflected in a perturbed mood state. Our purpose is to link the different behavioral outcomes occurring during withdrawal with specific biological brain mechanisms from the animal to the human being. Better understanding of the various biological mechanisms underlying withdrawal from alcohol will be the key to design and to apply appropriate pharmaceutical management, together with appropriate therapy aimed at inducing protracted abstinence.

Alcohol-Induced Disorders, Nervous System↗

PubMed2003

Gemcitabine increases systemic 5-fluorouracil exposure in advanced cancer patients.

A number of recent clinical trials testing the combination of 5-fluorouracil (5-FU) and gemcitabine in patients with advanced pancreatic adenocarcinoma have shown a significant clinical response rate, but also significant toxicity. As the two antimetabolites may interact at several biochemical levels along their pathways of activation, we investigated whether gemcitabine (GEM) affects 5-FU pharmacokinetics in cancer patients. Thus, we compared 5-FU pharmacokinetics in two groups of patients with various cancers who received the same schedule of 5-FU and folinic acid (FUFA), with or without GEM. There was a significant increase in systemic (5-FU) exposure and toxicity in the FUFA plus GEM group. Our finding may be useful in designing future studies of the combination in order to reduce the occurrence of side-effects and to maximise the antitumour activity.

Adult↗

PubMed2003

The response of macrophages to particles of resorbable polymers and their degradation products.

Alpha polyesters such as poly(L-lactide) and poly(glycolide) are biodegradable materials used in fracture fixation and they need to be assessed for problems associated with their degradation products. This study has compared cell responses to low molecular weight poly(L-lactide) particles, lactate monomer, poly(glycolide) particles and glycolic acid at cytotoxic and sub-cytotoxic concentrations. Murine macrophages were cultured in vitro and the release of lactate dehydrogenase (LDH), prostaglandin E(2) (PGE(2) and interleukin-1 alpha IL-1alpha was measured following the addition of particles or monomer. Experiments revealed that both the poly(L-lactide) and poly(glycolide) particles gave rise to dose dependent increases in LDH release and an increase in IL-1alpha and PGE(2) release. Comparisons of the poly(L-lactide) particles to the poly(glycolide) particles did not reveal any differences in their stimulation of LDH, IL-1alpha and PGE(2) release. The lactate and glycolate monomers did not increase PGE(2) or IL-1alpha release above control levels. There was no difference in biocompatibility between the poly(L-lactide) and poly(glycolide) degradation products both in particulate and monomeric form.

Journal Article↗

PubMed2003

Chemical composition and antifungal activity of the essential oil of Origanum virens on Candida species.

The composition and the antifungal activity of the essential oil of Origanum virens on Candida species were studied. The essential oil was obtained from the aerial parts of the plant by hydrodistillation and analyzed by GC and GC-MS. The oil was characterized by its high content of carvacrol (68.1 %) and its biogenetic precursors, gamma-terpinene (9.9 %) and p-cymene (4.5 %). The minimal inhibitory concentration (MIC) and the minimal lethal concentration (MLC) were used to evaluate the antifungal activity against Candida strains (7 clinical isolates and 3 ATCC type strains). The inhibition of germ tube formation and flow cytometry, using the fluorescent probe propidium iodide (PI), were used to evaluate their mechanisms of action. MIC and MLC values were similar for most tested strains, ranging from 0.16 to 0.32 microL/mL. Concentrations lower than MIC values strongly prevent germ tube formation. The fungicidal effect is primarily due to an extensive lesion of the membrane.

Antifungal Agents↗

PubMed2002

Neuroendocrine evaluation of 5-HT1A function in male alcoholic patients.

BACKGROUND: Preclinical evidences support the hypothesis of a serotonergic dysfunction in alcohol preference. In human, studies have demonstrated a serotonergic hypoactivity in alcoholism. However, little is known about the role of 5-HT1A receptors. METHODS: We assessed the hormonal (prolactin and cortisol) responses to flesinoxan (a highly potent and selective 5-HT1A agonist) in 12 male inpatients meeting DSM-IV criteria for alcohol dependence, 3 weeks after the last reported use of alcohol and antidepressants. These patients were compared to 10 male controls. RESULTS: There was a highly significant difference between alcoholic patients and controls for the area under the curve relative (AUCr) values of prolactin responses. AUCr values of cortisol responses to flesinoxan showed a trend towards lower values in alcoholics compared to controls. CONCLUSION: These results support the implication of the serotonergic system, and particularly a decreased sensitivity of post-synaptic 5-HT1A receptors, in alcoholism.

Adult↗

PubMed2002

5-HT1A dysfunction in borderline personality disorder.

BACKGROUND: A number of challenge studies have reported abnormalities of serotonergic function in borderline personality disorder (BPD). There are, however, problems with the pharmacological probes used in these studies since fenfluramine and m-CPP are not only serotonergic agents but also induce release of catecholamines, particularly dopamine. Therefore, we tested whether subjects with BPD showed a blunted prolactin (PRL) response to flesinoxan, a highly potent and selective 5-HT1A agonist. METHODS: Flesinoxan challenge test was carried out in 20 BPD in-patients and 20 healthy controls matched for gender but not for age. Since 16 BPD in-patients exhibited major depressive co-morbidity, a group of 20 depressed in-patients matched for gender but not for age was also included. RESULTS: BPD in-patients exhibited blunted PRL responses as compared to controls, whereas depressed in-patients did not differ from controls. Moreover, PRL responses were lower among BPD in-patients than among depressed in-patients. Among the BPD in-patients, PRL responses to flesinoxan were lower in patients with past history of suicide attempts (N = 8) than in those with a negative history. CONCLUSIONS: The results show major involvement of serotonergic function in BPD and are consistent with previous studies linking lower serotonergic activity with impulsivity. More particularly, our data suggest that BPD is characterized by lower 5-HT1A receptor sensitivity. Moreover, the data support the involvement of 5-HT1A activity in suicidal behaviour. However, this conclusion is limited because other hormonal responses such as ACTH and cortisol were not assessed, and because BPD was assessed by a self-report questionnaire and not a structured clinical interview.

Adult↗

PubMed2002

Changes in superoxide dismutase activity and photosynthetic pigment content during growth of marine phytoplankters in batch-cultures.

The ability of phytoplankton to cope with oxidative stress is one of the main factors that influence its survival in the marine environment, when senescence conditions prevail. In a first attempt to investigate the antioxidant strategies of different phytoplanktonic groups face to oxidative stress, the superoxide dismutase (SOD; EC 1.15.1.1) activity and photosynthetic pigment content along the growth curves of the dinoflagellate Lingulodinium polyedrum (Stein) Dodge, the prasinophycean Tetraselmis gracilis (Kylin) Butcher and the diatom Minutocellus polymorphus (Hargraves and Guillard) Hasle, von Stosch and Syvertsen were evaluated in batch-cultures. Total SOD activity was determined by an indirect method involving the inhibition of cytochrome c reduction. The contents of photosynthetic pigments were analysed by HPLC using a reverse phase column (RP-18), based on a ternary gradient. A peak of total SOD activity was detected at the beginning of the T. gracilis and M. polymorphus exponential growth. In L. polyedrum and M. polymorphus, SOD activity increased approximately three times by day 17 of growth, compared to the values obtained on day 3 (exponential phase) of the growth curve. All three species of microalgae had reduced SOD activity at the end of their growth. The levels of peridinin in L. polyedrum increased about 60% by day 17 of growth compared to the values obtained at exponential phase. Tetraselmis gracilis exhibited a remarkable increase (approximately 85%) in beta-carotene concentration after 10-14 days of growth whereas the beta-carotene levels in M. polymorphus decreased about 85% along its growth curve. These findings suggest that the antioxidant response during senescence in batch-cultures differ according to the species. Induction of SOD activity may occur either in the early exponential or stationary growth phases, which is important to prevent oxidative stress triggered by a number of factors that affects growth, such as nutrient and light availability.

Journal Article↗

PubMed2002

Venlafaxine: the relationship between dose, plasma concentration and clinical response in depressive patients.

The relationship between plasma drug level of venlafaxine and daily intake was studied in 89 major depressive inpatients. In addition, changes over time in severity were assessed weekly in a subgroup of 22 depressed patients using the Montgomery and Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression improvement scale. The results indicate a moderate correlation between daily doses and plasma concentrations, together with a higher relationship between improvement on the MADRS scale and concentration. Moreover, plasma concentrations (for venlafaxine and its predominant metabolite, O-desmethylvenlafaxine) up to 400 microg/l can be considered as effective, as already suggested in a previous study. No case of venlafaxine discontinuation occurred during the longitudinal study, and the incidence of adverse event, as estimated by the Target Emergent Symptoms and Side-effects scale, was low, suggesting that the drug is well tolerated for such plasma concentrations.

Adult↗

PubMed2001

Astaxanthin and peridinin inhibit oxidative damage in Fe(2+)-loaded liposomes: scavenging oxyradicals or changing membrane permeability?

Astaxanthin and peridinin, two typical carotenoids of marine microalgae, and lycopene were incorporated in phosphatidylcholine multilamellar liposomes and tested as inhibitors of lipid oxidation. Contrarily to peridinin results, astaxanthin strongly reduced lipid damage when the lipoperoxidation promoters-H(2)O(2), tert-butyl hydroperoxide (t-ButOOH) or ascorbate-and Fe(2+):EDTA were added simultaneously to the liposomes. In order to check if the antioxidant activity of carotenoids was also related to their effect on membrane permeability, the peroxidation processes were initiated by adding the promoters to Fe(2+)-loaded liposomes (encapsulated in the inner aqueous solution). Despite that the rigidifying effect of carotenoids in membranes was not directly measured here, peridinin probably has decreased membrane permeability to initiators (t-ButOOH > ascorbate > H(2)O(2)) since its incorporation limited oxidative damage on iron-liposomes. On the other hand, the antioxidant activity of astaxanthin in iron-containing vesicles might be derived from its known rigidifying effect and the inherent scavenging ability.

Antioxidants↗

PubMed2001

Preoperative positivity of serum tumor markers is a strong predictor of hematogenous recurrence of gastric cancer.

BACKGROUND AND OBJECTIVES: Preoperative positivity of serum tumor markers has been reported to be a prognostic factor in several neoplasms. The aim of this longitudinal study was to evaluate the correlation between CEA, CA 19-9, and CA 72-4 preoperative serum levels and the site of recurrence after curative surgery for gastric cancer. METHODS: One hundred sixty-seven patients resected for primary gastric cancer between January 1988 and June 1996 were considered. All patients were followed-up according to the same protocol, with a mean follow-up time of 45 +/- 39 months (range: 2-130). The correlation between marker positivity and the incidence of recurrence was studied by means of univariate and multivariate analyses. RESULTS: A tumor recurrence was found in 92 patients (55.1%). For each of the three markers, preoperative positivity was related to a higher incidence of hematogenous recurrences with respect to negative cases; univariate analysis also revealed a higher incidence of locoregional recurrences in CA 72-4-positive cases. At multivariate analysis, preoperative positivity for one or more tumor markers proved to be an independent predictor of hematogenous recurrences (P < 0.005, relative risk [RR] 4.82), in addition to lymph node involvement (P < 0.05, RR 3.82); no correlation between marker positivity and the onset of locoregional or peritoneal recurrences was found. CONCLUSIONS: Preoperative positivity for CEA, CA 19-9 or CA 72-4 is an independent risk factor for hematogenous recurrences of gastric carcinoma; this aspect should be considered in the option of using adjuvant chemotherapy after surgery for gastric cancer.

Adult↗

PubMed2001

Antioxidant modulation in response to metal-induced oxidative stress in algal chloroplasts.

To investigate adaptive responses to metal stress at the subcellular level, the oxidative balance in isolated chloroplasts was evaluated for the first time in the unicellular alga Gonyaulax polyedra exposed to the toxic metals Hg(2+), Cd(2+), Pb(2+), and Cu(2+). Different antioxidant responses were verified according to the metal and model of stress applied. Cells chronically exposed to metals exhibited high activity of the antioxidant enzymes superoxide dismutase and ascorbate peroxidase, high glutathione content, and decrease of peridinin levels, whereas no significant changes were detected for beta-carotene levels. In contrast, cells subjected to acute metal stress displayed twice as much beta-carotene but only a slight increase in superoxide dismutase and ascorbate peroxidase activities. The correlation of acute metal treatment and oxidative stress was inferred from the higher oxygen uptake and decreased reduced glutathione pool found in treated cells. In addition, increased oxidative damage to proteins and lipids occurred mainly in cells under acute stress. Pb(2+) was the most damaging toxicant, causing protein oxidation and lipid peroxidation even at chronic treatment. These results indicate that heavy metals are able to induce oxidative stress in chloroplasts of G. polyedra, particularly under acute conditions. Nevertheless, the maintenance of a high antioxidant capacity within chloroplasts seems to be an important strategy during acclimation of G. polyedra to chronic metal stress. By acting at the subcellular site, where oxidative stress is triggered, induction of such chloroplast antioxidants might be crucial for cell survival during exposure to heavy metals.

Ascorbate Peroxidases↗

PubMed2001

Clinical utility of CEA, CA 19-9, and CA 72-4 in the follow-up of patients with resectable gastric cancer.

BACKGROUND: The aim of this longitudinal study was to evaluate the effectiveness of the serum tumor markers CEA, CA 19-9, and CA 72-4 in the early diagnosis of recurrence of gastric cancer. METHODS: One hundred and thirty-three patients who had undergone potentially curative surgery were considered. Serum samples were obtained preoperatively, 1 week after surgery, and at every follow-up examination. Mean follow-up time for the entire patient population was 41 +/- 33 months, and 71 +/- 27 months for patients classified as disease-free. RESULTS: Preoperative positivity was 16% for CEA, 35% for CA 19-9, and 20% for CA 72-4. Recurrence of disease was found in 75 patients (56%). Marker sensitivity in recurrent cases was 44% for CEA, 56% for CA 19-9, and 51% for CA 72-4; the combined use of the three markers increased sensitivity to 87%, which reached 100% in patients with positive preoperative levels. Marker specificity, evaluated in 58 disease-free patients, was 79% for CEA, 74% for CA 19-9, and 97% for CA 72-4. CONCLUSIONS: The combined assay of CEA, CA 19-9, and CA 72-4 may be useful for early diagnosis of recurrence of gastric cancer; however, only CA 72-4 positivity should be considered a specific predictor of tumor recurrence.

Aged↗

PubMed2001

Reduced dopaminergic activity in depressed suicides.

Several data are available about the implication of the dopaminergic system in the control of inward-directed aggression. Previously, we suggested an involvement of D2-dopaminergic function in the expression of suicidal behavior by demonstrating a smaller growth hormone (GH) response to apomorphine, a dopaminergic agonist, in depressed patients with a history of suicide attempts in comparison to nonattempters. In the present study, the purpose was to analyze GH responses to apomorphine in depressive patients who later died by suicide. Our sample comprised eight male depressive inpatients who died by suicide within one year after hospitalisation. These patients were compared to 18 male major depressed inpatients who never attempted suicide. Mean GH peak responses to apomorphine differed significantly between suicide completers and controls (mean +/- SD): for GH peak, 7.6 +/- 4.1 ng/ml vs 18.9 +/- 14.2 ng/ml, U = 30, Z = -2.33, P = 0.02. Our results tend to confirm the role of dopamine in the biology of suicide in depression.

Adult↗

PubMed2001

Reduced dopamine function in depressed patients is related to suicidal behavior but not its lethality.

Several lines of evidence suggest a role for dopamine in the control of suicidal behaviour. Previously, we suggested an involvement of D2-dopaminergic function in the biology of suicide by demonstrating a smaller growth hormone (GH) response to apomorphine, a dopaminergic agonist, in depressed patients who later died by suicide. The purpose of the present study was to assess GH response to apomorphine in major depressed in-patients with a history of highly lethal suicide attempt compared to depressed patients with a low lethal lifetime suicide attempt history and non-attempters. The study was performed in a sample of 26 male depressed in-patients with a history of suicide attempt compared to 26 male depressed non-attempters. We observed a significant difference between suicide attempters and non-attempters (for GH peak, 6.3+/-5.1 ng/ml vs 15.8+/-14.2 ng/ml, F=10.3, df=1, 50, P=0.002). Moreover, GH peak responses to apomorphine did not differ between depressed patients with a high lethal lifetime suicide attempt history and patients who made low lethal lifetime suicide attempt. In conclusion, the results of the present study support a role for dopamine in the biology of suicidal behaviour. More specifically, an impaired GH response to apomorphine could be a marker of suicide risk.

Adult↗

PubMed2001

Differential activation by daphnetoxin and mezerein of PKC-isotypes alpha, beta I, delta and zeta.

Daphnetoxin, a mezerein derivative, was isolated from the stem bark of Daphne gnidium. Mezerein is a PKC activator that exhibits antileukemic properties. However, daphnetoxin and its analogue 12-hydroxydaphnetoxin were described as being devoid of this effect. In the present study daphnetoxin and mezerein were compared as PKC activators on classical (alpha and beta I), novel (delta) and atypical (zeta) isoforms, using an alternative in vivo yeast phenotypic assay. The aim was to clarify if daphnetoxin is a PKC activator and if the differences between the antiproliferative effect of mezerein and of its analogue daphnetoxin may be ascribed to differences on their potency or selectivity as PKC activators. Yeast samples expressing each of the mammalian PKC isoforms tested were incubated with daphnetoxin or mezerein. Growth inhibition caused by these drugs was assumed to be due to PKC activation since it did not occur when expression was not induced. Mezerein inhibited the growth of yeast expressing PKC alpha (IC(50) = 1190 +/- 237 nM; n = 20), PKC beta I (IC(50) = 908 +/- 46 nM; n = 20), and PKC delta (IC(50) = 141 +/- 25 nM; n = 20) but not of yeast expressing PKC zeta. Daphnetoxin also inhibited the growth of yeast expressing isoforms alpha, beta I and delta, being more potent than mezerein on PKC alpha (IC(50) = 536 +/- 183 nM; n = 20; P < 0.05), as potent as mezerein on PKC beta I (IC(50) = 902 +/- 129 nM; n = 20) and less potent than mezerein upon PKC delta (IC(50) = 3370 +/- 492 nM; n = 20; P < 0.05). These results show that daphnetoxin is a potent PKC activator but with a selectivity different from that of mezerein. It is suggested that the lack of antileukemic and antiproliferative effects of daphnetoxin may be due to its lower potency to activate PKC delta.

Antineoplastic Agents, Phytogenic↗

PubMed2001

Alpha-2-adrenoreceptors in depressed suicide attempters: relationship with medical lethality of the attempt.

Several lines of evidence tend to suggest a role for noradrenaline, and more specifically alpha-2-adrenoreceptors, in the biology of suicidal behavior. The purpose of this study was to assess the growth hormone (GH) response to clonidine, an alpha-2-adrenergic agonist, in majorly depressed inpatients with a history of highly lethal suicide attempt compared to depressed patients with a history of low lethal suicide attempt and nonattempters. Our sample included 20 male depressed inpatients with a history of suicide attempt compared to 20 male depressed nonattempters. We did not observe any significant difference between suicide attempters and nonattempters for GH peak values (2.4 +/- 2.9 vs. 4.1 +/- 3.7 ng/ml; F = 2.52, d.f. = 1, 38, p = 0.12). Moreover, GH peak responses to clonidine were not related to the degree of lethality of the attempt. The results of the present study do not support a major role for noradrenaline in the biology of suicidal behavior.

Adrenergic alpha-Agonists↗

PubMed2001

[Ultra-fast opiate detoxification under general anesthesia: preliminary results of the Liege protocol].

Many studies support the hypothesis of a substantial benefit in inducing an Opiate Receptor Blockade through a Rapid Opiate Detoxification under general Anaesthesia (RODA) in opiate dependent patients. However, prospective studies and long term evaluation of the technique are lacking. In order to evaluate long-term abstinence rates after a RODA among a sample of opiate addicts, a study was started in March 1999 at the University of Liège. To date, 45 patients were evaluated (mean age: 29 +/- 5 years) with a mean opiate dependence duration of 8 +/- 4 years. Most of them were both heroin and methadone dependent; 42.2% of them were included while 31.1% did not complete the whole inclusion procedure and 26.7% were excluded. None experienced severe withdrawal symptoms. At six months, abstinence rate was 67% and 46% at one year. These preliminary results suggest the interest of the procedure in carefully selected patients.

Adult↗