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S Pichini

Publications and source records attributed to S Pichini.

At least 37 records · Page 2Linked to original sources
PubMed2000

Pharmacokinetics and cytokine production in heroin and morphine-treated mice.

The parallelism between serum levels of heroin and morphine (M) metabolites and the production of interleukin-1beta (IL-1beta), interleukin-2 (IL-2), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1), and interferon-gamma (IFN-gamma) from murine splenocyte cultures following s.c. injection with 20 mg/kg heroin or M in C57/BL mice is described. The pharmacokinetic profiles of M and inactive morphine-3-glucuronide (M3G) in morphine-treated mice nearly overlapped those in heroin-treated mice, with the only difference being the presence of 6-monoacetylmorphine (AM) in profiles of the latter group. Heroin and M significantly increased production of IL-1beta, IL-2, TNF-alpha and IFN-gamma at 3, 20 and 40 min from treatment, peaking at 20 min, though the effect was very brief. At 24 h production was greatly inhibited, and this depressive effect lasted longer than the stimulatory effect. At 48 h only a partial recovery was observed. Heroin and M also had a highly stimulatory effect on the release of anti-inflammatory cytokines such as TGF-beta1 and IL-10, though this effect was observed after 120 min, peaking at 24 h and then somewhat decreasing at 48 h. This study demonstrates that the more rapid and pronounced immune response to heroin treatment was due to the presence of AM. Both heroin and M produced a biphasic effect on cytokine production: the central opioid or non-opioid receptors are involved in exogenous opiod-induced stimulatory effects, whereas peripheral opioid or non-opioid receptors are involved in depressive effects. Deficient or excess expression of these key mediators may predispose the host to aberrant defence mechanisms.

Animals↗
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

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↗
PubMed2000

Drugs in nails: physiology, pharmacokinetics and forensic toxicology.

In recent years, drug analysis in keratinised matrices, such as hair and nails, has received considerable attention because of several advantages over drug testing methodologies employing body fluids, such as urine or serum. For example, keratinic matrices, such as finger- and toenails, can accumulate drugs during long term exposure. Drugs are incorporated into nails by a double mechanism: (i) deposition into the root of the growing nail via the blood flow in the nail matrix; and (ii) incorporation via the nail bed during growth from the lunula to the beginning of the free margin. Together, these account for a wide retrospective window of drug detection. Nails can provide a good forensic matrix for the detection of drugs of abuse. Indeed, the international literature has reported the use of nail analysis in postmortem detection of drugs of abuse, drug testing in the workplace and drug screening to detect prenatal exposure, even though further studies are needed for correct interpretation of the data obtained. Another application of drug analysis in nails consists of the possibility of detecting the presence of an antimycotic at the site of action during antifungal therapy for patients with onychomycosis. When available, this evidence has permitted drug treatment of a shorter duration and reduced toxicity. However, so far the potential of drug monitoring in nails still lacks harmonisation and validation of analytical methodologies and a better comprehension of the possible correlation between drug concentrations in the matrix and period of exposure.

Forensic Medicine↗
PubMed2000

[Analysis of drugs and abuse substances in the keratinic matrix].

Hair analysis of xenobiotics is an ideal addendum to blood and urine analysis because it can reveal information that is not available through analysis of the other two specimens. However, there are still some unresolved issues that may affect the legal acceptance of hair testing to quantify drug consumption or exposition. The present paper shows hypotheses on mechanisms of drug incorporation in the hair shaft, variability factors pending on incorporation, methodology for hair collection and extraction, analytes determination and finally data presentation and interpretation.

Hair↗
PubMed2000

[Immunomodulator properties of ecstasy (MDMA)].

In vitro exposure to ecstasy (3,4-methylenedioxymethamphetamine, MDMA) alters some immune parameters such as T-cell regulatory function, cytotoxic T-lymphocyte activity, natural killer cell activity and macrophage function. Administration of MDMA in rats produces a suppression of lympho-proliferation response and a decrease in circulating lymphocytes, accompanied by an increase in plasma corticosterone. It was postulated a direct action of MDMA on lymphocytes or rather an indirect action mediated by the hypothalamic pituitary adrenal axis (HPA-AXIS) and/or the sympathetic nervous system (SNS). Acute MDMA treatment effected on healthy-volunteers produces an immune dysfunction associated with pharmaceutical characteristics and so with MDMA plasma concentrations. There is a decrease in CD4+ T-cells and functional responsiveness of lymphocytes, while percentage of natural killer cells increases. A contemporary rise of cortisol plasma concentrations supports the hypothesis of MDMA-induced release of corticotrophin-releasing factor from the hypothalamus and subsequent HPA-axis and SNS activation.

Animals↗
PubMed1999

Determination of lorazepam in plasma and urine as trimethylsilyl derivative using gas chromatography-tandem mass spectrometry.

A procedure based on gas chromatography-tandem mass spectrometry for identification and quantitation of lorazepam in plasma and urine is presented. The analyte was extracted from biological fluids under alkaline conditions using solid-phase extraction with an Extrelut-1 column in the presence of oxazepam-d5 as the internal standard. Both compounds were then converted to their trimethylsilyl derivatives and the reaction products were identified and quantitated by gas chromatography-tandem mass spectrometry using the product ions of the two compounds (m/z 341, 306 and 267 for lorazepam derivative and m/z 346, 309 and 271 for oxazepam-d5 derivative) formed from the parent ions by collision-induced dissociation in the ion trap spectrometer. Limit of quantitation was 0.1 ng/ml. This method was validated for urine and plasma samples of individuals in treatment with the drug.

Anti-Anxiety Agents↗
PubMed1999

Immunomodulating properties of MDMA alone and in combination with alcohol: a pilot study.

Cell-mediated immune response after the administration of MDMA alone and in combination with alcohol was evaluated in a randomized, double-blind, double-dummy, cross-over pilot clinical trial conducted in four healthy MDMA consumers who received single oral doses of 75 mg MDMA (n = 2) or 100 mg MDMA (n = 2), alcohol (0.8 mg/kg), MDMA and alcohol, or placebo. 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 the CD4 T/CD8 T-cell ratio as well as in the percentage of mature T lymphocytes, probably because of a decrease in both the percentage and absolute number of T helper cells. The decrease in CD4 T-cell counts and in the functional responsiveness of lymphocytes to mitogenic stimulation was dose-dependent. The correlation between MDMA pharmacokinetics and the profile of MDMA-induced immune dysfunction suggests that alteration of the immune system may be mediated by the central nervous system. Alcohol consumption produced a decrease in T helper cells, B lymphocytes, and PHA-induced lymphocyte proliferation. Combined MDMA and alcohol produced the greatest suppressive effect on CD4 T-cell count and PHA-stimulated lymphoproliferation. Immune function was partially restored at 24 hours. These results provide the first evidence that recreational use of MDMA alone or in combination with alcohol alters the immunological status.

Adjuvants, Immunologic↗
PubMed1999

Determination of opiates and cocaine in hair as trimethylsilyl derivatives using gas chromatography-tandem mass spectrometry.

An analytical method for the determination of heroin, 6-monoacetylmorphine, morphine, codeine, cocaine, benzoylecgonine, and cocaethylene in human hair using gas chromatography-tandem mass spectrometry is presented. The analytes were extracted from finely cut hair with methanol at 56 degrees C for 18 h in the presence of nalorphine as the internal standard. After the incubation, methanol was evaporated to dryness, and all the analytes, except heroin, cocaine, and cocaethylene, were converted to their trimethylsilyl derivatives. The reaction products were identified and quantitated using product ions formed from the parent ions by collision-induced dissociation in the ion-trap mass spectrometer. This method provided excellent sensitivity and specificity for analytes at the concentrations usually found in the keratin matrix.

Cocaine↗
PubMed1999

Quantitative aspects of drugs of abuse in urine samples: intercollaborative studies conducted in the European Union.

A description of a quantification performance by laboratories taking part in two intercollaborative studies (surveys 1 and 2) carried out in 1993 (n = 195) and 1994 (n = 228), respectively, on urine drug testing in the European Union is presented. The performance of laboratories that quantified at least one substance (33.8% and 34.6% out of the total laboratories in surveys 1 and 2, respectively) is reported as a function of the analytic technique applied for quantification, the number of parameters investigated, the precision and accuracy of results obtained, and the influence of availability of reference material, including deuterated drug-standard analogue solutions provided in survey 2. Quantification of different drugs of abuse was mainly carried out by gas chromatography coupled to mass spectrometry (63.1% of analyses in survey 1 vs. 68.6% in survey 2). It should be noted about the data obtained that the results for quantification were not particularly satisfactory in terms of precision and accuracy (CV mean = 62.8 in survey 1 and 50.4 in survey 2 and error % mean = 12.7 in survey 1 and 18.6 in survey 2). The provision of reference materials increased the number of substances quantified (45.3% in survey 1 vs. 51.8% in survey 2) and improved the performance (CV mean of matching laboratories when quantifying matching substances: 50.1% in survey 1 vs. 35.5% in survey 2). The impact of a "learning factor" (the opportunity to be challenged a second time and to correct past errors) and the influence of the provision of deuterated analogues in survey 2 was investigated in a population of repeater laboratories that quantified both in surveys 1 and 2 (55 vs. 63 laboratories, respectively). According to the European experience reported, it may be observed that laboratories able to afford quantitative analyses provided better overall analytic performance. This is probably because quantification implies some validation of the analytic procedure. Participation in interlaboratory comparison programs also aimed at assessing the performance of quantitative analyses should be considered a quality asset for laboratories involved in drug testing.

Data Collection↗
PubMed1998

Simultaneous determination of epirubicin, doxorubicin and their principal metabolites in human plasma by high-performance liquid chromatography and electrochemical detection.

A high-performance liquid chromatographic method with electrochemical detection has been developed for the simultaneous determination of epirubicin, 13-S-dihydroepirubicin, doxorubicin and 13-S-dihydrodoxorubicin in human plasma. An aliquot of 200 microl plasma, spiked with internal standard, was extracted by solid-phase extraction using polymeric adsorbent columns. Chromatography was performed using a C18 reversed-phase column with a mobile phase consisting of water-acetonitrile (71:29, v/v) containing 0.05 M Na2HPO4 and 0.05% v/v triethylamine adjusted to pH 4.6 with citric acid. Linearity of the method was obtained in the concentration range of 1-500 ng/ml for all the analytes. Analytical recoveries of the analytes ranged from 89 to 93%. The assay can be used for the simultaneous determination of the four analytes, or for epirubicin and its metabolite or doxorubicin and its metabolite, using the other parent drug as an internal standard. The method was applied to analyze human plasma samples from patients treated with epirubicin using doxorubicin as an internal standard.

Antibiotics, Antineoplastic↗
PubMed1998

Issues in methodology and applications for therapeutic drug monitoring of fluoxetine and norfluoxetine enantiomers.

A standardization of the analytical procedures for monitoring of fluoxetine and norfluoxetine enantiomers is described. Simultaneous determination of fluoxetine and norfluoxetine enantiomers in plasma and serum was performed by high-performance liquid chromatography with a chiral stationary phase, using ultraviolet absorbance detection. The analytes were extracted from the biologic matrix by alkalinization with NaOH and solid-phase extraction. Stability studies were conducted in EDTA, lithium-heparinized plasma and in serum spiked with the analytes stored at +4 degrees C for 1 week and at -20 degrees C for 1 month. Furthermore, stability studies in NaOH and in the extraction solvents were executed. Using this methodology, EDTA plasma is the most suitable matrix for drug monitoring, even if the storage should not exceed 3 weeks at -20 degrees C. Furthermore, the biologic sample should be left in NaOH for a short time before solid-phase extraction to prevent a degradation of matrix, which would interfere with the chromatographic analysis.

Chromatography, High Pressure Liquid↗
PubMed1997

Hair analysis for nicotine and cotinine: evaluation of extraction procedures, hair treatments, and development of reference material.

Analysis of nicotine and cotinine in human hair can provide information on nicotine intake and exposure to environmental tobacco smoke over a long period of time. Nonetheless, to better assess the usefulness of hair analysis to determine smoking habits or exposures, all procedures have to be standardized. Various solvents were tested as washing solvents to eliminate external contamination from nicotine. Dichloromethane was found effective when used for two washes prior to the extraction. Basic and acid digestion of hair followed by solid phase extraction with Extrelut-3 glass column using dichloromethane:isopropyl alcohol (9:1) as eluting mixture both gave good recoveries of nicotine and cotinine, when compared with extractions reported in the literature. The extraction method was free from substances, which could interfere in the chromatographic analysis. Furthermore, the addition of methanolic HCl to the eluting mixture prevented the loss of nicotine during the evaporation step before chromatography. Chromatography was performed using a reversed-phase column and a U.V. detection at 254 nm. Furthermore, hair treatments (dyes, permanent wave, hydrogen peroxide) caused a major decrease in the nicotine content in hair, and a smaller effect on cotinine levels. However, the effect of various treatments was not reproducible. Several attempts to produce reference materials were carried out. Nicotine and cotinine standard solutions at different concentrations were added to blank hair soaked in dimethylsulfoxide, methanol and water.

Chromatography, High Pressure Liquid↗
PubMed1997

The analysis of nicotine in infants' hair for measuring exposure to environmental tobacco smoke.

Hair samples were collected from 24 infants (3-36 months) exposed and non-exposed to environmental tobacco smoke. Hair was washed in dichloromethane, digested in NaOH, extracted by solid-phase extraction and analyzed by high-performance liquid chromatography to determine the content of nicotine and cotinine. Nicotine concentration in non-exposed infants (1.3 +/- 1.7 ng/mg hair) was significantly different from that in occasionally exposed infants (6.8 +/- 2.1 ng/mg hair) and that in infants passively exposed to smoke (15.4 +/- 6.7 ng/mg hair). Cotinine could be measured only in passive smokers infants. These findings suggest the possibility of monitoring exposure to environmental tobacco smoke in infants by using nicotine measurement in hair rather than in urine, blood or saliva.

Biomarkers↗
PubMed1997

Cytokine production in saquinavir treated mice.

The effects of chronic and acute saquinavir treatment on murine cytokine production were investigated in both plasma and splenocyte cultures. Cytokine plasma levels were below the detection limit in both saquinavir treated mice and in control mice with the exception of IFN-gamma, whose levels were detectable in 15 day treated mice. Saquinavir was found to increase interferon gamma (IFN-gamma) and interleukin-2 (IL-2) production from stimulated splenocytes. Saquinavir also caused a marked reduction of transforming growth factor-beta 1 (TGF-beta 1) in supernatants of splenocytes cultures. Conversely, interleukin-1 beta (IL-1 beta), interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-alpha) production was not modified by drug treatment. In the present paper we hypothesized that this protease inhibitor may be involved in the immunoregulatory cytokine network.

Animals↗
PubMed1996

Drug monitoring in nonconventional biological fluids and matrices.

Determination of the concentration of drugs and metabolites in biological fluids or matrices other than blood or urine (most commonly used in laboratory testing) may be of interest in certain areas of drug concentration monitoring. Saliva is the only fluid which can be used successfully as a substitute for blood in therapeutic drug monitoring, while an individual's past history of medication, compliance and drug abuse, can be obtained from drug analysis of the hair or nails. Drug concentrations in the bile and faeces can account for excretion of drugs and metabolites other than by the renal route. Furthermore, it is important that certain matrices (tears, nails, cerebrospinal fluid, bronchial secretions, peritoneal fluid and interstitial fluid) are analysed, as these may reveal the presence of a drug at the site of action; others (fetal blood, amniotic fluid and breast milk) are useful for determining fetal and perinatal exposure to drugs. Finally, drug monitoring in fluids such as cervical mucus and seminal fluid can be associated with morpho-physiological modifications and genotoxic effects. Drug concentration measurement in nonconventional matrices and fluids, although sometimes expensive and difficult to carry out, should therefore be considered for inclusion in studies of the pharmacokinetics and pharmacodynamics of new drugs.

Biological Availability↗