Biomedical subjects

J Segura

Publications and source records attributed to J Segura.

At least 19 recordsLinked to original sources

PubMed2001

Changes in androgenic steroid profile due to urine contamination by microorganisms: a prospective study in the context of doping control.

Urine contamination by microorganisms may affect the interpretation of urinalysis in different areas of clinical diagnosis. This is particularly relevant in doping control. A prospective study was designed to assess the effects of urine contamination by selected pathogens on the endogenous androgenic steroid profile. Pooled urine from a healthy male volunteer with standard steroid profile compared with reference values for the Caucasian population was sterilized by filtration and stored in sterile glass tubes. Aliquots were inoculated with known amounts of 15 different organisms (bacteria, fungi, and moulds) and incubated at 37 degrees C for 2 weeks. Different markers of urine contamination, such as pH, deconjugation of steroids, and metabolic by-products, were determined. Alkalization of urinary pH was not a reliable indicator of urine contamination as several organisms grew in this medium and no alteration of this parameter was found. In uncontaminated urine, less than 10% of steroid glucuronide conjugates were spontaneously hydrolyzed. Higher rates of hydrolysis for sulfate conjugates were found. An unconjugated fraction higher than 10% of the total amount of testosterone was a reliable indicator of urine contamination. However, microbial production of testosterone or epitestosterone was not detected. In contrast, a few organisms were able to synthesize 5alpha-androstanedione, 5beta-androstanedione, and androstenedione using endogenous steroids as substrates.

Androgens↗

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↗

PubMed2000

Nonclassical photon statistics in single-molecule fluorescence at room temperature

The fluorescence of single terrylene molecules in a crystalline host is investigated at room temperature by scanning confocal optical microscopy. Photon arrival times are analyzed in terms of interphoton time distributions, second order correlation functions, and the variance of the photon number probability distribution. Antibunching at short times and bunching behavior for longer times is observed, associated with sub- and super-Poissonian statistics, respectively. A rate-equation analysis of the molecular level populations indicates an accelerated reverse intersystem crossing.

Journal Article↗

PubMed2000

Hair analysis and detectability of single dose administration of androgenic steroid esters.

Detection of anabolic steroids in hair samples has been possible only in fatal cases or in cases of high-continuous dosages. In order to verify the possibility of detecting an acute administration, a sensitive and specific assay has been developed for the simultaneous determination of testosterone, nandrolone and some of their esters in hair. The analytes were extracted from finely cut hair with methanol-trifluoroacetic acid overnight. After the incubation, the mixture was evaporated to dryness, redissolved and extracted with hexane. The dried organic layer was silanised and analysed by GC-MS and GC-MS-MS. A sensitivity of at least 20 pg injected was obtained for all the analytes. In guinea pigs treated with a single intramuscular dose of 10 mg/kg nandrolone decanoate, neither nandrolone decanoate nor nandrolone were found in hair collected after 13 days, while both compounds were clearly detectable after four repeated doses (each dose every 3-4 days) of 20 mg/kg nandrolone decanoate. Neither nandrolone decanoate nor nandrolone could be detected in hair from a male healthy volunteer 1 month after treatment with 50 mg nandrolone decanoate, while his urine still tested highly positive for the main nandrolone metabolite (> 100 ng/ml). Testosterone esters could not be detected in hair of healthy subjects collected respectively 3, 2 and 1 month after a single intramuscular administration of 250 mg testosterone enanthate (five subjects), a single intramuscular coadministration of 25 mg testosterone propionate plus 110 mg testosterone enanthate (one subject), or a single oral administration of 120 mg testosterone undecanoate (three subjects). Otherwise, hair analysis revealed an increase of testosterone concentration corresponding to the period of treatment. Analysis of blood and urine samples confirmed the absorption of those compounds. At the sensitivity achieved by the present method, no detection of nandrolone, nandrolone decanoate nor testosteron esters in hair seems to be obvious after a single dose administration.

Adult↗

PubMed2000

Derivatization procedures for the detection of beta(2)-agonists by gas chromatographic/mass spectrometric analysis.

An evaluation of derivatization procedures for the detection of beta(2)-agonists is presented. The study was performed with the beta(2)-agonists bambuterol, clenbuterol, fenoterol, formoterol, salbutamol, salmeterol and terbutaline. Different derivatizating agents were employed, aiming to obtain derivatives with high selectivity to be used in the gas chromatographic/mass spectrometric analysis of beta(2)-agonists in biological samples. Trimethylsilylation was compared with different agents and the role of some catalysts was evaluated. Acylation, combined trimethylsilylation and acylation, and the formation of cyclic methylboronates were also studied. Sterical hindrance caused by different substituents at the nitrogen atom of the beta-ethanolamine lateral chain of beta(2)-agonist molecules is mainly responsible for differences in the abundances of the derivatives obtained. The use of catalysts produces an increase in the derivatization yield, especially for compounds with low steric hindrance (substituents with primary and secondary carbon atoms). The formation of trimethylsilyl (TMS) ethers is not influenced by structural molecular differences when only hydroxy groups are involved in derivatization. Combined trimethylsilylation and acylation showed that compounds with a secondary carbon atom linked to the nitrogen atom form mainly N-TFA-O-TMS derivatives, with a small amount of N-TMS-O-TMS derivatives. Compounds with tert-butyl substituents at the amino group (bambuterol, salbutamol and terbutaline) formed O-TMS derivatives as the main products, although a limited amount of trifluoroacylation at the nitrogen atom also occurred. Cyclic methylboronates were formed with bambuterol, clenbuterol, formoterol, salbutamol and salmeterol. Owing to hydroxy substituents in unsuitable positions for ring formation, this procedure was not effective for fenoterol and terbutaline. Mass spectra of different derivatives and tentative fragmentation profiles are also shown. For screening purpose (e.g. sports drug testing), derivatization with MSTFA or BSTFA alone is recommended as a comprehensive derivatization technique for beta(2)-agonists owing to minimal by-product formation; formation of cyclic methylboronates can be useful for confirmation purposes. Detection limits were obtained for the TMS and cyclic methylboronate derivatives using the derivatizing reagents MSTFA and trimethylboroxine, respectively. For most of the compounds, lower detection limits were found for the TMS derivatives.

Acetamides↗

PubMed2000

Transcatheter occlusion of complex atrial septal defects.

Percutaneous device occlusion of secundum atrial septal defects (ASDs) is becoming an accepted alternative to surgical closure. This method allows us to evaluate patients with complex conditions for treatment. From a total of 70 patients with ASD evaluated for percutaneous closure, we selected for analysis 28 who had complex conditions. The mean age was 36+/-23 yr (range, 4-72). Six had heart failure, and of these six, three had atrial fibrillation. At cardiac catheterization, the pulmonary pressure was 47+/-24 mm Hg, and the QP/QS was 1.7+/-0.4; two patients had bidirectional shunt and systemic pulmonary pressure. Two patients received a buttoned device and 26 an Amplatzer septal occluder. The groups of patients with complex conditions were separated into the following groups. Group I (n = 4) underwent combined treatment of associated anomalies. Two patients had pulmonary stenosis, one had mitral stenosis, and one had an aortic root-left atrium fistula. They were treated in or during with the same procedure by combined transcatheter techniques (balloon valvuloplasty and fistula occlusion) before ASD occlusion. Group II (n = 9) had multiple defects (cribiform or two separate holes). They were treated with a single device in five instances and with two separate devices in four cases. Group III (n = 14) had large (32+/-3 mm) single defects. Nine of them underwent successful implantation using a device 33+/-3 mm in diameter; in the remaining five patients the device was removed because of instability. Group IV (n = 3) had residual defects after previous partial device occlusion. All three defects were successfully occluded with a second device. No movement or interference with the first device was observed. Group V (n = 6) had severe pulmonary hypertension (86+/-16 mm Hg). Immediately after ASD occlusion we observed significant relief in these patients (67+/-14 mm Hg; P<0.01). There were no major complications; all 23 patients with successful implants were discharged without symptoms 2-7 days later; one patient with atrial fibrillation recovered sinus rhythm. The follow-up (8+/-5 mo) Doppler echo study showed complete ASD occlusion in 22 patients and a peak pulmonary pressure of 30+/-14 mm Hg. We conclude that transcatheter occlusion of ASDs is an effective and safe treatment for patients with complex anatomic or physiopathologic conditions, as evaluated by short-term follow-up.

Adolescent↗

PubMed2000

Liver cirrhosis is reverted by urokinase-type plasminogen activator gene therapy.

Liver cirrhosis represents a worldwide health problem and is a major cause of mortality. Cirrhosis is the result of extensive hepatocyte death and fibrosis induced by chronic alcohol abuse and hepatitis B and C viruses. Successful gene therapy approaches to this disease may require both reversal of fibrosis and stimulation of hepatocyte growth. Urokinase-type plasminogen activator (uPA) may serve this function, as it is an initiator of the matrix proteolysis cascade and induces hepatocyte growth factor expression. In a rat cirrhosis model, a single iv administration of a replication-deficient adenoviral vector encoding a nonsecreted form of human uPA resulted in high production of functional uPA protein in the liver. This led to induction of collagenase expression and reversal of fibrosis with concomitant hepatocyte and improved liver function. Thus, uPA gene therapy may be an effective strategy for treating cirrhosis in humans.

Animals↗

PubMed2000

Engineering pancreatic islets.

Pancreatic islets are neuroendocrine organs that control blood glucose homeostasis. The precise interplay of a heterogeneous group of cell populations (beta, alpha, delta and PP cells) results in the fine-tuned release of counterbalanced hormones (insulin, glucagon, somatostatin and pancreatic polypeptide respectively). Under the premises of detailed knowledge of the physiological basis underlying this behaviour, two lines of investigation might be inferred: generating computational and operational models to explain and predict this behaviour and engineering islet cells to reconstruct pancreatic endocrine function. Whilst the former is being fuelled by new computational strategies, giving biophysicists the possibility of modelling a system in which new "emergent" properties appear, the latter is benefiting from the useful tools and strategic knowledge achieved by molecular, cell and developmental biologists. This includes using tumour cell lines, engineering islet cell precursors, knowledge of the mechanisms of differentiation, regeneration and growth and, finally, therapeutic cloning of human tissues. Gaining deep physiological understanding of the basis governing these processes is instrumental for engineering new pancreatic islets.

Animals↗

PubMed2000

Specific c-K-ras gene mutations as a tumor-response marker in locally advanced rectal cancer treated with preoperative chemoradiotherapy.

BACKGROUND: Forty percent of patients with colorectal cancer develop mutations in the K-ras gene. OBJECTIVE: Our objective was to evaluate whether the presence of c-K-ras gene mutations is a useful tumor-response marker in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy. MATERIAL AND METHODS: Thirty seven patients with locally advanced rectal cancer were treated with preoperative chemoradiotherapy. Four to six weeks later, surgery was performed. Specimens were classified according to the UICC-AJC classification. A segment of the tumor was obtained to analyze specific c-K-ras gene mutations. Restriction fragment length polymorphism (RFLP) and single strand confirmation polymorphism (SSCP) techniques were used with a set of probes to detect specific c-K-ras mutations in codons 12, 13, and 61. The 37 patients were divided into Group A (with mutations) and Group B (without mutations). RESULTS: All 37 patients completed the scheduled treatment. Group A consisted of 12 patients, whose tumors were classified and specific c-K-ras mutations were located as follows: eight in codon 12, two in codon 13, and one in codon 61. Group B consisted of 25 patients. The tumors were classified and there were more early-stage tumors in Group A, whereas in Group B there were more advanced-stage tumors (P = .05, respectively). The mean follow-up was 36.2+/-18.3 months. All Group A patients survived, whereas 8 of the 25 patients in Group B died due to progressive metastatic disease. Survival in Group A was 100%, whereas in Group B it was 59% (P = .03). CONCLUSIONS: The presence of specific c-K-ras mutations is an indicator of tumor response in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy and surgery. Therefore, responding patients may be more amenable to less radical surgical procedures based on c-K-ras mutations.

Adenocarcinoma↗

PubMed2000

Modeling study of exocytosis in neuroendocrine cells: influence of the geometrical parameters.

Exocytosis in neuroendocrine cells is a process triggered by Ca(2+). A Monte Carlo simulation of secretion has been developed which, together with the diffusion of calcium, buffered by endogenous and/or exogenously added chelators, also accounts for the dynamics of exocytosis for a pool of readily releasable vesicles. Different distributions of channels and vesicles (random or correlated) are studied. A local study of exocytosis is carried out by obtaining capacitance time courses for the different types of release-ready vesicle pools (correlated or not with Ca(2+) channels). Also, depending upon the kinetic constants for the exocytotic process, we study the levels of local Ca(2+) needed to trigger secretion. Our simulations show that a strong heterogeneity in the calcium concentrations at the different sites of exocytosis is a requirement for reproducing the experimentally observed biphasic response in chromaffin cells in situ (Voets, T., E. Neher, and T. Moser. 1999. Neuron. 23:607-615). Correlated nonuniform distributions of channels and vesicles and the existence of diffusion barriers are shown to quantitatively explain the experimental data on chromaffin cells in situ. The first description requires a deeply heterogeneous distribution, with vesicles attached to the channels or far from them, but never at middle distances. The second description is able to reproduce biphasic release even for uniformly (readily releasable) distributed vesicles. We quantify the degree of inhomogeneity in the distribution of vesicles and how porous the diffusion barriers should be to account for the observed biphasic response.

Animals↗

PubMed2000

Monte carlo simulation of 3-D buffered Ca(2+) diffusion in neuroendocrine cells.

Buffered Ca(2+) diffusion in the cytosol of neuroendocrine cells is a plausible explanation for the slowness and latency in the secretion of hormones. We have developed a Monte Carlo simulation to treat the problem of 3-D diffusion and kinetic reactions of ions and buffers. The 3-D diffusion is modeled as a random walk process that follows the path of each ion and buffer molecule, combined locally with a stochastic treatment of the first-order kinetic reactions involved. Such modeling is able to predict [Ca(2+)] and buffer concentration time courses regardless of how low the calcium influx is, and it is therefore a convenient method for dealing with physiological calcium currents and concentrations. We study the effects of the diffusional and kinetic parameters of the model on the concentration time courses as well as on the local equilibrium of buffers with calcium. An in-mobile and fast endogenous buffer as described by, Biophys. J. 72:674-690) was able to reach local equilibrium with calcium; however, the exogenous buffers considered are displaced drastically from equilibrium at the start of the calcium pulse, particularly below the pores. The versatility of the method also allows the effect of different arrangements of calcium channels on submembrane gradients to be studied, including random distribution of calcium channels and channel clusters. The simulation shows how the particular distribution of channels or clusters can be of relevance for secretion in the case where the distribution of release granules is correlated with the channels or clusters.

Animals↗

PubMed2000

Truncated active matrix metalloproteinase-8 gene expression in HepG2 cells is active against native type I collagen.

BACKGROUND/AIMS: Excess type I collagen accumulation is a major feature of fibrotic diseases such as liver cirrhosis. Reversion of this disease has not been fully accomplished. Physiologically, collagen is degraded by interstitial collagenases, neutrophil collagenase (MMP-8) being the most active against type I collagen. Introduction of MMP-8 gene into liver cells could be an advantageous tool to potentiate fibrosis degradation. METHODS: We cloned latent and active MMP-8 genes in prokaryotic and eukaryotic expression vectors and an adenoviral vector. Transfection of MMP-8 in HepG2 was effectuated by CaPO4, polylysine-lactose (P-L) and adenoviral transduction, and cells and culture supernatant were harvested 72 h after transfection for analysis of MMP-8 expression by reverse transcription-polymerase chain reaction and collagenolytic activity. RESULTS AND CONCLUSIONS: We show that a truncated neutrophil collagenase (tMMP-8) lacking a portion of the carboxy terminus and with an intact aminoterminus (latent; l-tMMP-8) or a truncated amino terminus (active; a-tMMP-8) has enzymatic activity against native type I collagen, and the activity was inhibited by EDTA, 1,10-phenanthroline and TIMP-1. Both MMP-8 mRNA (latent and active) were detected by polymerase chain reaction in cells transfected with CaPO4, P-L and adenoviral transduction; however, relative expression of MMP-8 was enhanced when the plasmid was delivered as a P-L complex and increased by adenoviral infection. Finally, a-tMMP-8 cDNA was cloned in a vector under transcriptional control of a regulated promoter (PEPCK-a-tMMP-8). HepG2 cells transfected with the PEPCK-a-tMMP-8 plasmid DNA up-regulated expression of a-tMMP-8 after incubation of the cells with butyryl-cAMP and glucagon, while stimulation with insulin slightly down-regulated its expression. Recombinant MMP-8 expressed by HepG2-transduced cells can efficiently degrade soluble type I collagen, which is potentially useful for gene transfer therapies.

Collagen↗

PubMed2000

Non-linear pharmacokinetics of MDMA ('ecstasy') in humans.

AIMS: 3,4-Methylenedioxymethamphetamine (MDMA, commonly called ecstasy) is a synthetic compound increasingly popular as a recreational drug. Little is known about its pharmacology, including its metabolism and pharmacokinetics, in humans in controlled settings. A clinical trial was designed for the evaluation of MDMA pharmacological effects and pharmacokinetics in healthy volunteers. METHODS: A total of 14 subjects were included. In the pilot phase six received MDMA at 50 (n=2), 100 (n=2), and 150 mg (n=2). In the second phase eight received MDMA at both 75 and 125 mg (n=8). Subjects were phenotyped for CYP2D6 activity and were classified as extensive metabolizers for substrates, such as MDMA, whose hepatic metabolism is regulated by this enzyme. Plasma and urine samples were collected throughout the study for the evaluation of MDMA pharmacokinetics. Body fluids were analysed for the determination of MDMA and its main metabolites 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxy-methamphetamine (HMMA) and 4-hydroxy-3-methoxy-amphetamine (HMA). RESULTS: As the dose of MDMA administered was increased, volunteers showed rises in MDMA concentrations that did not follow the same proportionality which could be indicative of nonlinearity. In the full range of doses tested the constant recovery of HMMA in the urine combined with the increasing MDMA recovery seems to point towards a saturation or an inhibition of MDMA metabolism (the demethylenation step). These observations are further supported by the fact that urinary clearance was rather constant while nonrenal clearance was dose dependent. CONCLUSIONS: It has previously been postulated that individuals genetically deficient for the hepatic enzyme CYP2D6 (about 10% of the Caucasian people) were at risk of developing acute toxicity at moderate doses of MDMA because the drug would accumulate in the body instead of being metabolized and inactivated. The lack of linearity of MDMA pharmacokinetics (in a window of doses compatible with its recreational use) is a more general phenomenon as it concerns the whole population independent of their CYP2D6 genotype. It implies that relatively small increases in the dose of MDMA ingested are translated to disproportionate rises in MDMA plasma concentrations and hence subjects are more prone to develop acute toxicity.

3,4-Methylenedioxyamphetamine↗

PubMed2000

Comparative study of home and office blood pressure in hypertensive patients treated with enalapril/HCTZ 20/6 mg: the ESPADA study.

The introduction and generalization of 24-h ambulatory blood pressure (BP) monitoring has shown the clinical relevance of home BP. The aim of this study was to assess the validity of home-measured BP for monitoring and controlling patients with arterial hypertension while on a homogeneous treatment. An additional objective was to establish the degree of office BP control obtained. This was a prospective, longitudinal, observational and multicenter study in a cohort of 156 patients of both sexes, aged over 18 years and with essential hypertension. All of them received the fixed combination enalapril/HCTZ 20/6 mg as the only hypertensive agent for at least 4 weeks previously. Office BP was the average of three measurements. For home BP, a semi-automated device (OMRON HEM 705 CP) was used. The patients measured their BP twice a day for 2 consecutive days. The average differences between the two measuring methods were low, but significant: 3.99 mmHg for systolic BP (SBP; p < 0.05), 2.02 mmHg for diastolic BP (DBP; p < 0.05). Pearson's regression coefficient between the office and home values was highly significant (p < 0.0001) for SBP, DBP and heart rate. Home BP measurement was highly reproducible as shown by the high within-class correlation coefficient for individual measurements on the first day compared with the second: 0.88 (95% confidence interval, CI 0.82-0.92; p < 0.00001) for SBP and 0.89 for DBP (95% CI 0.83-0.93; p < 0.00001). The percentage of patients with strict office DBP and SBP control (< 140/90 mmHg) was 61.3% and with DBP control (<90 mmHg) 92%. In conclusion, in the ESPADA study, the application of home BP measurement is valid, reproducible and shows a high correlation with office BP.

Age Factors↗

PubMed2000

Distinction of inhaled and oral salbutamol by urine analysis using conventional screening procedures for doping control.

Salbutamol administration in athletes is permitted only by inhalation, for the management of asthma. The authors discuss different criteria for suspecting oral use of salbutamol, taking into account the data obtained by application of two conventional screening procedures for doping control: gas chromatography/mass spectrometry (GC/MS) and enzyme-linked immunosorbent assay (ELISA). Urine samples obtained after administration of oral and inhaled salbutamol to asthmatic and nonasthmatic swimmers were analyzed using both analytical approaches. As expected, concentrations obtained by the ELISA test (detection of total salbutamol) were higher than those obtained using the GC/MS procedure (detection of nonsulfated salbutamol). After oral administration, the ELISA test detected significantly higher salbutamol concentrations than those detected after inhalation, reflecting the greater doses administered orally. Urine samples with total salbutamol greater than 1400 ng/mL were obtained after oral doses, but no sample reached this value after inhaled doses. Higher concentrations of nonsulfated salbutamol have also been detected after oral intake, although there is an overlap between the distributions of concentrations after oral and inhaled doses. A cut-off concentration of 500 ng/mL can be used for nonsulfated salbutamol to select suspicious samples, giving 11.8% false negative results and 4.3% false positive results. An additional criterion evaluated was the androsterone-salbutamol peak height ratio, which was lower after oral doses because of the higher concentrations of salbutamol in urine. This ratio was lower than 2 for all the samples collected after oral administration, although 6.8% false positive samples resulted because of low concentrations of androsterone in female urine. Several possibilities for detecting suspicious samples from athletes who have taken prohibited oral salbutamol are available with conventional screening procedures in doping control.

Administration, Inhalation↗

PubMed2000

Immunomodulating activity of MDMA.

MDMA (3,4-methylenedioxymethamphetamine) use can cause neurochemical, behavioral and endocrine alterations, similar to those produced by exposure to acute stress, suggesting its potential as a "chemical stressor." It is known that stressful stimuli can produce a depression of immune function and an alteration in immune cells distribution. In vitro exposure to MDMA resulted in a modulation of several immune functional parameters such as T-cell regulatory function, cytotoxic T-lymphocyte activity, natural killer cell activity and macrophage function. Administration of MDMA in rats produced a rapid and sustained suppression of induced lymphocytes proliferation and a significant decrease in circulating lymphocytes. These alterations in rat immune function were accompanied by a significant rapid increase in plasma corticosterone concentrations. It was postulated that the result of altered induced proliferation response of lymphocytes could have been due to a combined effect of direct action of MDMA on lymphocytes and to the activation of the hypothalamic pituitary adrenal axis (HPA axis) and/or the sympathetic nervous system (SNS) via central mechanisms. In humans, acute MDMA treatment produced a time-dependent immune dysfunction associated with MDMA plasma concentrations. Although total leukocyte count remained unchanged, there was a decrease in CD4+ T-cells and functional responsiveness of lymphocytes to mitogenic stimulation, while percentage of natural killer cells significantly increased. A rise of cortisol plasma concentrations similar to that observed in the rat model supported the hypothesis of MDMA-induced release of corticotrophin-releasing factor from the median eminence of the hypothalamus and subsequent HPA axis and SNS activation. The present findings indicate that MDMA ingestion may represent a potential health hazard for an increased risk of immune system-related diseases.

Animals↗

PubMed2000

Pharmacology of MDMA in humans.

MDMA given at recreational doses (range tested 50 to 150 mg) to healthy volunteers, produced mydriasis and marked increases in systolic and diastolic blood pressure, heart rate, and pupillary diameter. MDMA induced changes on oral temperature. The time course of this observation was biphasic, as a slight decrease at 1 h and a slight increase at 2 and 4 h were observed. MDMA induced a slight dose-dependent impairment on psychomotor performance. MDMA produced a marked rise in plasma cortisol and prolactin concentrations. The elimination half-life of MDMA was about 8-9 h. Drug concentrations increased, and a parallel increase in physiologic and hormonal measures was observed. Both peak concentrations and peak effects were obtained between 1 and 2 h and decreased to baseline values 4-6 h after drug administration.

Analysis of Variance↗

PubMed2000

Cord serum cotinine as a biomarker of fetal exposure to cigarette smoke at the end of pregnancy.

This study investigated the association between biomarkers of fetal exposure to cigarette smoke at the end of pregnancy, cotinine in cord serum and in maternal and newborn urine samples, and quantitative measurement of smoking intake and exposure evaluated by maternal self-reported questionnaire. Study subjects were 429 mothers and their newborns from a hospital in Barcelona, Spain. A questionnaire including smoking habits was completed in the third trimester of pregnancy and on the day of delivery. Cotinine concentration in cord serum was associated with daily exposure to nicotine in nonsmokers and with daily nicotine intake in smokers. The geometric mean of cotinine concentration in cord serum statistically discriminated between newborns from nonexposed and exposed nonsmoking mothers, and between these two classes and smokers, and furthermore was able to differentiate levels of exposure to tobacco smoke and levels of intake stratified in tertiles. Urinary cotinine levels in newborns from nonsmoking mothers exposed to more than 4 mg nicotine daily were statistically different from levels in two other categories of exposure. Cotinine concentration in urine from newborns and from mothers did not differentiate between exposure and nonexposure to environmental tobacco smoke (ETS) in nonsmoking mothers. Cord serum cotinine appeared to be the most adequate biomarker of fetal exposure to smoking at the end of pregnancy, distinguishing not only active smoking from passive smoking, but also exposure to ETS from nonexposure.

Adult↗