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Biomedical subjects

M Farré

Publications and source records attributed to M Farré.

At least 19 recordsLinked to original sources
PubMed2002

Analysis and toxicity of methomyl and ametryn after biodegradation.

The controlled biodegradation of ametryn and methomyl has been performed, in accordance with the OECD Zahn-Wellens/EMPA procedure, by use of an enriched mixture of activated sludge collected from three domestic waste-water-treatment plants (WWTP). During the process concentrations of ametryn and methomyl in the water samples were isolated by solid-phase extraction (SPE); recovery rates were 98.9 and 93.2 for methomyl and ametryn, respectively. Liquid chromatography-mass spectrometry (LC-MS) was used to determine final pesticide concentrations and for metabolite identification. The efficiency of aerobic biodegradation of ametryn and methomyl was evaluated by measuring both the decrease in the concentration of the pesticides and global properties such as the chemical oxygen demand (COD). The acute toxicity of ametryn and methomyl was evaluated by use of the ToxAlert100 biological test, which is based on inhibition of the bioluminescence of Vibrio fischeri. There was significant correlation between results from primary and ultimate biodegradation and those from determination of toxicity. Pesticide concentrations were always reduced to below the limit of detection in less than 17 days. High COD removal (90-96%) was achieved in 28 and 18 days for methomyl and ametryn, respectively.

Biodegradation, Environmental↗
PubMed2002

Pesticide toxicity assessment using an electrochemical biosensor with Pseudomonas putida and a bioluminescence inhibition assay with Vibrio fischeri.

Two different toxicity tests, an electrochemical biosensor Cellsense and a bioluminescence inhibition assay ToxAlert were performed in order to establish and compare the acute toxicity responses of different types of raw and spiked water for a selected group of pesticides. The selected compounds were endosulfan, chlorfenvinphos, dimethoate, fenamiphos, ametryn, deltamethrin and alpha-cypermethrin; all of them are used in large quantities for agricultural purposes. In the first step, the study of the toxicity responses for each individual pesticide with Milli-Q water was carried out. Next, the toxic responses of different mixtures of these pesticides in different water matrices, i.e., Milli-Q water, surface water, groundwater and wastewater were studied in order to evaluate (i) device advantages and limitations for the toxicity evaluation of real environmental samples, (ii) antagonistic or synergistic effects and (iii) the influence of the water matrices. The survey of pesticides in real samples was carried out using a combined method involving both chemical analysis and toxicity bioassays. Chemical analysis involved the use of solid-phase micro-extraction (SPME) followed by gas chromatography with electron capture detection (GC/ECD) or thermoionic specific detection (GC/TSD) with mass spectrometric confirmation (GC/MS).

Biosensing Techniques↗
PubMed2002

High-performance liquid chromatography with electrochemical detection applied to the analysis of 3,4-dihydroxymethamphetamine in human plasma and urine.

Metabolic activation in the disposition of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") has been implicated in some of its pharmacological and toxicological effects, with the major metabolite 3,4-dihydroxymethamphetamine (HHMA) as a putative toxicant through the formation of thioether adducts. We describe the first validated method for HHMA determination based on acid hydrolysis of plasma and urine samples, further extraction by a solid-phase strong cation-exchange resin (SCX, benzenesulfonic acid), and analysis of extracts by high-performance liquid chromatography with electrochemical detection. The chromatographic separation was performed in an n-butyl-silane (C4) column and the mobile phase was a mixture of 0.1 M sodium acetate containing 0.1 M 1-octanesulphonic acid and 4 mM EDTA (pH 3.1) and acetonitrile (82:18, v/v). Compounds were monitored with an electrochemical cell (working potentials 1 and 2, +0.05 and +0.35 V, respectively, gain 60 microA). A mobile phase conditioning cell with a potential set at +0.40 V was connected between the pumping system and the injector. Calibration curves were linear within the working concentration ranges of 50-1000 microg/L for urine and plasma. Limits of detection and quantification were 10.5 and 31.8 microg/L for urine and 9.2 and 28.2 microg/L for plasma. Recoveries for HHMA and DHBA (3,4-dihydroxybenzylamine, internal standard) were close to 50% for both biological matrices. Intermediate precision and inter-day accuracy were within 3.9-6.5% and 7.4-15.3% for urine and 5.0-10.8% and 9.2-13.4% for plasma.

Calibration↗
PubMed2002

Effect of ingestion of virgin olive oil on human low-density lipoprotein composition.

OBJECTIVE: To measure the incorporation of oleic acid and antioxidants (phenols and vitamin E) to low density lipoprotein (LDL) after acute and short-term ingestion of virgin olive oil. To study whether this incorporation contributes to an increase in LDL resistance to oxidation. SETTING: Department of Food and Nutrition, University of Barcelona, Spain and Department of Lipids and Cardiovascular Epidemiology, IMIM, Barcelona, Spain. SUBJECTS: Sixteen healthy volunteers aged 25-65 y. DESIGN AND INTERVENTIONS: To observe the change in the fatty acid profile, vitamin E, phenolic compounds and LDL oxidation-related variables after the postprandial phase and after daily ingestion of olive oil for one week. RESULTS: Few changes were observed in the postprandial phase. However, after a week of olive oil consumption there was an increase in oleic acid (P=0.015), vitamin E (P=0.047), phenolics (P=0.021) and lag time (P=0.000), and a decrease in the maximum amount of dienes (P=0.045) and oxidation rate (P=0.05). CONCLUSION: After ingestion of virgin olive oil, an increase in antioxidants and oleic acid in LDL was observed as well as an improvement of LDL resistance to oxidation. Our results support the idea that daily ingestion of virgin olive oil could protect LDL from oxidation. SPONSORSHIP: This study was supported by a research grant from Spain (ALI 97-1607-C02-02).

Adult↗
PubMed2002

Cell-mediated immune response in MDMA users after repeated dose administration: studies in controlled versus noncontrolled settings.

Acute administration of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") produces time-dependent immune dysfunction in humans. Recreational use of MDMA generally includes repeated drug consumption, often in association with other drugs, such as alcohol and cannabis. In the laboratory setting, repeated MDMA administration to healthy MDMA consumers produced a time-dependent immune dysfunction similar to that observed with the ingestion of a single dose, and the first of the two administrations paralleled the time-course of MDMA-induced cortisol stimulation kinetics and MDMA plasma concentrations. A significant decrease in CD4 T-helper cells with simultaneous increase in natural killer (NK) cell and a decrease in functional responsiveness of lymphocytes to mitogenic stimulation was observed. Response to the second dose was either long-lasting compared with the first dose or disproportionate and did not show any parallelism with cortisol and MDMA plasma concentrations. This circumstance extended the critical period during which immunocompetence is highly impaired as a result of MDMA use. Accumulation of MDMA in the body of a poor metabolizer induced higher immunomodulatory effects with statistically significant differences in NK cell function compared with extensive metabolizers. When basal values of lymphocyte subsets were examined in a population of recreational MDMA users participating in different clinical trials, alterations in several immunological parameters were observed. The absolute number of lymphocytes, in particular T lymphocytes and CD4 T-helper cell subsets, showed a trend toward reduced values, although cell counts were within normal limits. By contrast, NK cells in MDMA consumers were reduced to one-third of those from healthy persons. A statistically significant decrease in affected immune parameters was recorded during a 2-year observation period in a subgroup of recreational MDMA users. These permanent alterations in immunologic homeostasis may result in impairment of general health and subsequent increased susceptibility to infection and immune-related disorders.

Amphetamine-Related Disorders↗
PubMed2001

Effects of repeated doses of MDMA ("ecstasy") on cell-mediated immune response in humans.

Cell-mediated immune response after the administration of two repeated doses of 100 mg 3,4-methylenedioxymethamphetamine (MDMA) at 4-hour and 24-hour intervals was evaluated in two randomised, double-blind and cross-over clinical trials conducted in healthy male MDMA consumers. MDMA produced a time-dependent decrease in the CD4/CD8 T-cell ratio due to a decrease in the number of CD4 T-helper cells, a decrease in the functional responsiveness of lymphocytes to mitogenic stimulation, and a simultaneous increase in natural killer cells. In case of two 100 mg MDMA doses given 4 hour apart, immune alterations produced by the first dose were strengthened by the second one. At 24 hours after treatment, statistically significant residual effects were observed for all the altered immune parameters after the administration of two MDMA doses if compared to single dose and placebo. In the second clinical trial, the second 100 mg MDMA dose given 24 hours after the first dose produced immunological changes significantly greater than those induced by the initial drug administration and which seemed to show a delayed onset. Significant residual effects were observed for all the immune parameters as late as 48 hours after the second dose. These results show that repeated administration of MDMA with both a short and a long time interval between doses extends the critical period following MDMA administration, already observed after a single dose, in which immunocompetence is severely compromised.

CD4-CD8 Ratio↗
PubMed2001

Modulation of rate of onset and intensity of drug effects reduces abuse potential in healthy males.

Low, medium, and high doses of flunitrazepam were tested in three independent randomized, double-blind, balanced cross-over, placebo-controlled trials to study the influence of rate of onset of effects and dose administered on its acute effects. Three groups of 12 healthy male volunteers received six oral doses of placebo or flunitrazepam in slow and fast onset conditions as follows: six capsules of 0.16 mg (slow) and a single capsule of 0.8 mg (fast) in the low dose trial; six 0.25 mg (slow) and a single 1.25 mg (fast) capsules for medium dose; and six 0.4 mg (slow) and a single 2 mg (fast) capsule for high dose. At each dose level, slow or fast increasing flunitrazepam plasma concentrations lead to similar peak levels, but induced differential subjective and behavioral effects. In addition to objective and subjective sedation, flunitrazepam induced some pleasurable feelings, which were more intense in the fast than in the slow conditions. At the highest dose, unpleasant sedative effects surmounted positive effects, while at the lowest dose pleasurable effects were of low intensity. At the medium dose, the balance between pleasurable and unpleasant feelings resulted in euphorigenic effects, which were evident in the fast condition but were blunted in the slow condition.

Adolescent↗
PubMed2001

Effects of glucose and fructose on motility patterns of dog spermatozoa from fresh ejaculates.

This study was performed to gain insight about how fructose and glucose modulate dog spermatozoa motility in the absence of other motility-modulating factors. Incubation of dog spermatozoa from fresh ejaculates in a basal medium without sugars for 60 min at 37 degrees C induced a progressive decrease in the percentage of motile spermatozoa and in some mean motility parameters, such as mean velocity (VAP), linear coefficient (LIN) and dance (DNC), and an increase in the mean frequency of head displacement (BCF). This indicates a progressive loss of linearity and an increase in oscillatory movement. Addition of 10 mM fructose prevented these effects. Incubation in a basal medium with 10 mM glucose for 60 min at 37 degrees C provoked a fast and intense decrease of LIN and a slight increase of DNC, inducing a less linear and more oscillatory mean movement. Neither fructose nor glucose modified the percentage of motile spermatozoa. The response to both sugars was dose-dependent, with differences appearing at concentrations as low as 1 mM. An analysis of the spermatozoa subpopulation placed above the 95th percentile of the whole population and a factorial analysis of the data indicated that the changes in the mean values of the motility parameters were mainly due to a specific motile subpopulation that had a strong reaction to the two sugars. Our results indicate that fructose, at concentrations from 1 to 10 mM, induced a more linear and less oscillatory motility pattern than glucose. Moreover, from our results we suggest the presence of motile dog sperm subpopulations with an increased sensitivity to fructose and glucose.

Animals↗
PubMed2001

Characterization of wastewater toxicity by means of a whole-cell bacterial biosensor, using Pseudomonas putida, in conjunction with chemical analysis.

A new amperometric biosensor based on inhibition of Pseudomonas putida has been developed to assess the acute toxicity of wastewater. This system uses the biological component immobilized on disposable screen-printed electrodes. The responses for a selected group of polar organic standard substances were studied using Pseudomonas putida as biological component. The results have been compared with responses obtained using the same system and Escherichia coli as biological component and with the bioluminescence inhibition of Vibrio fisheri using ToxAlert 100. Different properties, e.g. the standard deviation (SD) of the data, the goodness of fit (R2) and the standard deviation (Syx) of the vertical distances of the points from the inhibition curve, the 50% effective concentration (EC50) and the toxicity units (TII50) of the standard substance, were calculated and compared. This biosensor was used to assess the acute toxicity of real wastewater samples collected at different wastewater treatment plants (WWTP). Finally, a sequential solid-phase extraction (SSPE) procedure followed by liquid chromatography-mass spectrometry (LC-MS) was used to determine the polar organic toxic substances present in the wastewater samples.

Biosensing Techniques↗
PubMed2001

3,4-Dihydroxymethamphetamine (HHMA). A major in vivo 3,4-methylenedioxymethamphetamine (MDMA) metabolite in humans.

There is evidence that some heavy users of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) show signs of neurotoxicity (a cognitive dysfunction, a larger incidence of psychopathology). It has been postulated that the catechol intermediates of methylenedioxyamphetamines such as 3,4-dihydroxymethamphetamine (HHMA), a metabolite of MDMA, may play a role in their neurotoxicity by formation of thioether adducts. This study describes the first validated method for HHMA determination in plasma and urine by strong cation-exchange solid-phase extraction high-performance liquid chromatography/electrochemical detection (HPLC/ED) analysis. The method has been applied for the determination of HHMA in plasma and urine samples from a clinical study in healthy volunteers of MDMA and provides preliminary kinetic data on this metabolite. HHMA appeared to be a major MDMA metabolite with plasma concentrations as high as the parent compound. Thus, HHMA C(max) (154.5 microg/L) and AUC(0-24h)(1990.9 microg/L h) were similar to those obtained in previously published reports for MDMA (181.6 microg/L and 1465.9 microg/L h, respectively). The 24-h urinary recovery of HHMA accounted for 17.7% of the MDMA dose administered and increases the total 24 h recovery of MDMA and metabolites to 58% of the 100 mg dose administered. The determination of HHMA in plasma and urine samples is of interest in order to establish its relevance in MDMA metabolism and its possible contribution to MDMA neurotoxicity in humans. Its validation showed appropriate accuracy and precision for its use in pharmacokinetic studies.

Adult↗
PubMed2001

Prevalence and risk of gingival enlargement in patients treated with anticonvulsant drugs.

BACKGROUND: Predictors of gingival enlargement in patients treated with anti-epileptics have not been previously assessed. This study was conducted to determine, with the aid of two indices that score vertical and horizontal overgrowth, the prevalence and risk factors for gingival enlargement in patients treated with phenytoin and other anticonvulsant drugs. MATERIALS AND METHODS: A cross-sectional study was conducted and data from 59 patients taking antiepileptics were compared with 98 controls. Gingival enlargement was evaluated with two indices to score vertical overgrowth [Gingival overgrowth index (GO] and horizontal overgrowth [Miranda-Brunet index (MB)]. Gingival index, plaque index, and probing depth were also evaluated. RESULTS: The prevalence of gingival enlargement was significantly higher (P < 0.0001) for both indices in the anticonvulsants treated groups than in the control group. Gingival overgrowth was significantly higher for both indices in the phenytoin group than in the non phenytoin group. Among the possible risk factors, only the gingival index showed a significant association with gingival enlargement. For the MB index the risk of gingival enlargement (odds ratio) associated to phenytoin therapy and other anticonvulsants therapy were 52.6 (13.5-205) and 6.6 (1.5-28.2). Gingival index-adjusted odds ratios for the same drugs were 5.7 (1.3-24.7) and 18.1 (2-158), respectively. The concordance between GO and MB indices in the control group and in the phenytoin-group and non phenytoin-group showed a Kappa value of 0.773 and 0.697, respectively. CONCLUSION: This study reports significant differences in the prevalence and severity of gingival overgrowth in two groups of patients, one treated with phenytoin, and another treated with other anticonvulsants. Gingival inflammation is a significant risk factor for gingival enlargement in these patients.

Adolescent↗
PubMed2001

Analytical methodology for the detection of benzodiazepine consumption in opioid-dependent subjects.

Benzodiazepines are frequently abused by heroin users, but not all compounds have shown the same abuse liability. We developed an analytical method that was able to detect various benzodiazepine compounds in a single run. Enzymatically hydrolyzed urine underwent a liquid-liquid extraction procedure with chloroform/isopropanol (9:1) at pH 8-9 followed by a solid-liquid clean-up (Bond Elut TCA C18) to obtain appropriate extracts for HPLC analysis. Mobile phase composition was optimized by means of the linear solvation energy relationship methodology based on Reichardt's normalized solvatochromic parameter (E(T)N). The method was validated for the simultaneous detection and quantitation of alprazolam, alpha-hydroxyalprazolam, oxazepam, 7-aminoflunitrazepam, flunitrazepam, nordiazepam, lorazepam, and diazepam. The prevalence of benzodiazepine consumption in 229 opioid-dependent subjects on methadone-maintenance treatment was 48%. Oxazepam and nordiazepam were the benzodiazepines most frequently recoved in urine samples. The prevalence of alprazolam use (40%) was higher than that of flunitrazepam (10%).

Adult↗
PubMed2001

Sweat testing of MDMA with the Drugwipe analytical device: a controlled study with two volunteers.

Rapid on-site tests for the analysis of drugs of abuse in unconventional specimens (e.g., sweat) have recently been developed. Two healthy volunteers familiar with the effects of methylenedioxymethamphetamine (MDMA) were given 100 mg of the drug as a single oral dose. MDMA and its main metabolite 4-hydroxy-3-methoxymethamphetamine (HMMA) were determined in plasma and urine by gas chromatography-mass spectrometry (GC-MS). MDMA was also investigated in sweat with the Drugwipe (an immunochemical strip test). Subjects' armpits were swabbed for 10 s at 0 time (predose) and at 2, 6, 8, 12, and 24 h after MDMA administration. MDMA consumption could be detected using Drugwipe at 2 h and for as long as 12 h after drug administration. However, in one of the volunteers, a faint color change appeared at 0 time, when plasma and urine tested negative for MDMA and did not disappear even 48 h later. Plasma concentrations of MDMA and HMMA measured by GC-MS peaked at 2-4 h, and values greater than 20 ng/mL for MDMA and of 40 ng/mL for HMMA were still detected at 24 h. Urine tested positive by GC-MS for MDMA and HMMA in the 48-h collection period. These findings preliminarily support sweat testing with Drugwipe for monitoring MDMA use.

Humans↗
PubMed2001

Prevalence and risk of gingival enlargement in patients treated with nifedipine.

BACKGROUND: Gingival enlargement is a known side effect of nifedipine use. This study was conducted to determine the prevalence and risk factors for gingival enlargement in nifedipine-treated patients. METHODS: A cross-sectional study was conducted in a primary care center. Data from 65 patients taking nifedipine were compared with 147 controls who had never received the drug. All patients were examined for the presence of gingival enlargement using 2 different indices: vertical gingival overgrowth index (GO) in 6 points around each tooth, and horizontal MB index in the interdental area. Gingival index, plaque index, and probing depth were also evaluated. RESULTS: The prevalence of gingival enlargement was significantly higher in nifedipine-treated cases than in controls (GO index, 33.8% versus 4.1%; MB index, 50.8% versus 7.5%, respectively). Higher gingival and plaque indices were observed in patients taking nifedipine. Among the possible risk factors, only the gingival index showed a significant association with gingival enlargement. The risk (odds ratio [OR]) of gingival enlargement associated with nifedipine therapy was 10.6 (3.8-29.1) for the GO index and 14.4 (6-34.6) for the MB index. Gingival index-adjusted ORs were 9.6 (3.3-28.1) and 9.7 (3.9-23.3), respectively. In the subset of high nifedipine exposure patients, the odds ratio for gingival enlargement increased to 17.4 (5.3-56.3) for the GO index and 23.6 (7.7-72.3) for the MB index. The concordance between GO and MB indices showed a kappa value of 0.689 in controls and 0.642 in patients treated with nifedipine. CONCLUSIONS: Patients taking nifedipine are at high risk for gingival enlargement, and gingivitis acts as a predisposing factor.

Adolescent↗
PubMed2001

Acute effects of 3,4-methylenedioxymethamphetamine alone and in combination with ethanol on the immune system in humans.

Cell-mediated immune response and release of cytokines after the administration of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") alone and in combination with ethanol were assessed in a double blind, randomized, crossover, controlled clinical trial. Six healthy male recreational users of MDMA participated in four different experimental sessions, with a washout interval between sessions of 1 week, in which single oral doses of MDMA (100 mg), ethanol (0.8 g/kg), the combination of both drugs, and placebo were tested. Acute MDMA administration produced a time-dependent immune dysfunction in association with serum concentrations of the drug as well as cortisol stimulation kinetics. Although total leukocyte count remained unchanged, there was a decrease in the CD4 T/CD8 T-cell ratio due to a decrease in both the percentage and absolute number of CD4 T-helper cells and simultaneous increase in natural killer (NK) cells. Ethanol consumption produced a decrease in T-helper cells and B lymphocytes. The combination of MDMA and ethanol caused the highest suppressive effect on CD4 T cells and increasing effect in NK cells. Drugs treatment produced a high increase of immunosuppressive cytokines (transforming growth factor-beta and interleukin-10) and a switch from Th1-type cytokines (interleukin-2 and interferon-gamma) to Th2-type cytokines (interleukin-4 and interleukin-10). Disregulation in the production of pro- and anti-inflammatory cytokines with an unbalance toward anti-inflammatory response was also observed. The immune function shows a trend toward baseline levels at 24 h after MDMA kinetics. This transient defect in immunological homeostasis, if temporarily repeated, might alter the immune response with a risk for the general health status.

Adult↗
PubMed2001

Usefulness of saliva for measurement of 3,4-methylenedioxymethamphetamine and its metabolites: correlation with plasma drug concentrations and effect of salivary pH.

BACKGROUND: Saliva is an alternative biologic matrix for drugs-of-abuse testing that offers the advantages of noninvasive, rapid, and easy sampling. We studied the excretion profile of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolites in both saliva and plasma, as well the effect of the drug on salivary pH. METHODS: Saliva and plasma samples were obtained from eight healthy MDMA consumers after ingestion of a single 100-mg dose of the drug. Concentrations of MDMA and its main metabolites, 3,4-methylenedioxyamphetamine (MDA) and 4-hydroxy-3-methoxymethamphetamine (HMMA), in saliva and plasma were measured by gas chromatography-mass spectrometry. Apparent pharmacokinetic parameters for MDMA in saliva were estimated, and the saliva-to-plasma ratio at each time interval was calculated and correlated with salivary pH. RESULTS: MDMA, MDA, and HMMA were detected in saliva. Salivary concentrations of MDMA were 1728.9-6510.6 microg/L and peaked at 1.5 h after drug intake. This was followed by a progressive decrease, with a mean concentration of 126.2 microg/L at 24 h. The saliva-to-plasma ratio was 32.3-1.2, with a peak of 18.1 at 1.5 h after drug administration. Salivary pH seemed to be affected by MDMA administration; pH values decreased by 0.6 units (mean pH values of 6.9 and 6.8 at 1.5 and 4 h after drug administration vs predose pH of 7.4). CONCLUSIONS: Measurement of MDMA in saliva is a valuable alternative to determination of plasma drug concentrations in both clinical and toxicologic studies. On-site testing is also facilitated by noninvasive and rapid collection of salivary specimens.

3,4-Methylenedioxyamphetamine↗