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Biomedical subjects

R Cordero

Publications and source records attributed to R Cordero.

17 recordsLinked to original sources
PubMed2005

Validation of techniques to detect illicit heroin use in patients prescribed pharmaceutical heroin for the management of opioid dependence.

BACKGROUND: The clinical implementation and evaluation of heroin substitution programmes have been confounded by the lack of objective and validated biomarkers for illicit heroin use in patients prescribed pharmaceutical heroin. This study examined the capacity to detect illicit heroin use by gas chromatography-mass spectrometry (GC-MS) analysis of urine samples for the presence of opium impurities common to illicit, but not pharmaceutical heroin. AIMS: To characterize the diagnostic properties of the metabolites of noscapine and papaverine in comparison to morphine as a gold-standard marker of illicit heroin use; and to examine the relationships between the self-reported time since most recent heroin use and the detection of these opioids in urine. DESIGN: A cross-sectional study of 52 opioid-dependent patients in treatment (not prescribed heroin), who self-reported illicit heroin use within the preceding 2 weeks. Self-report data regarding recent drug use and a urine sample were collected. GC-MS analyses of urines were conducted and reported by laboratory staff blinded to self-report data. FINDINGS: The metabolites of papaverine (hydroxypapaverine and dihydroxypapeverine) were found to have high sensitivity, specificity and negative predictive values as markers for illicit heroin use compared to the 'gold-standard' morphine. Other opioids, including 6-mono-acetylmorphine (6-MAM), codeine and noscapine metabolites (e.g. meconine) were less adequate in detecting heroin use. CONCLUSIONS: GC-MS detection of papaverine metabolites in urine appears to be suitable method of identifying illicit heroin use for clinical and research purposes.

Adult↗
PubMed2001

Qualitative screening for drugs of abuse in hair using GC-MS.

A previously described method for the analysis of hair has been modified to include analysis for amphetamines, benzodiazepines, cocaine and its metabolites, methadone and its metabolite, and phencyclidine in addition to opiates on a sample of hair. The samples of hair were washed twice with dichloromethane and cut into 1-mm segments prior to extraction with methanol at 45 degrees C for 18 h. The extracts were split into two parts; both were evaporated to dryness. One half of the extract was derivatized using MBTFA for analysis of amphetamines, and the other half was derivatized using MTBSTFA for analysis of the remaining drugs. The extracts were analyzed using electron impact gas chromatography-mass spectrometry operating in selected ion monitoring mode. In total, 18 drugs of abuse/metabolites could be detected. The method was used to screen 20 hair samples from patients attending a methadone-maintenance clinic.

Gas Chromatography-Mass Spectrometry↗
PubMed2000

Analysis of urine for drugs of abuse using mixed-mode solid-phase extraction and gas chromatography-mass spectrometry.

A method for the simultaneous analysis of urine for the major drugs of abuse is described. The analytical procedure uses solid-phase extraction (SPE), gas chromatography-mass spectrometry (GC-MS) and a semi-automated identification process. It allows simultaneous extraction, derivatization and analysis of acidic, neutral and basic drugs from urine. Urine samples were subjected to enzymatic hydrolysis followed by SPE using Bakerbond narc-2 columns. The eluant was selectively derivatized with N-methyl-bis-trifluoroacetamide (MBTFA) and N-methyl-N-trimethylsilyltrifluoroacetamide + 1% trimethylchlorosilane. Analysis was performed using a GC-MS system operating in full scan mode. A simple macro programme was written to enhance the mass spectra identification capabilities of the MS software by producing extracted ion chromatograms (EIC) for the drugs of interest. Once a suspect compound was indicated by EIC, the mass spectrum of the compound was searched manually against reference libraries for positive identification and the retention time checked against that of the standard. This procedure has increased both the amount and the reliability of information given to clinicians without increasing the cost per sample. The system has been in routine operation for 24 months, processing up to 40 urine samples per day, with a usual turn-around time of 48 h.

Evaluation Studies as Topic↗
PubMed1998

Serum levels of thyroxine-binding prealbumin, C-reactive protein and interleukin-6 in protein-energy undernourished children and normal controls without or with associated clinical infections.

We measured the levels of thyroxine-binding prealbumin (TBPA), C-reactive protein (CRP), and interleukin-6 (IL-6) in sera from protein-energy undernourished and control children either without or with associated clinical infections. Levels of TBPA were significantly lower in undernourished than in control children without clinical infections. Mean serum TBPA concentration was also significantly lower in both clinically infected undernourished and control children than in those of the same nutritional status but without overt infections. Significant positive correlations were observed between the concentration of TBPA and the Z-scores of weight for age, height for age, and weight for height in all children without clinical infections, which disappeared in clinically infected children. CRP and IL-6 increased to approximately similar levels in sera from undernourished and control children with overt infections. An inverse correlation between the levels of TBPA and CRP and a significant positive correlation between the concentration of CRP and IL-6 were observed in children with associated clinical infections. Serum IL-6 and TBPA showed a small negative relationship in patients with overt infections. Thus, TBPA is a sensitive marker of undernutrition only in the absence of clinical infections, and the capacity to increase production of IL-6 and CRP during infections is preserved in protein-energy undernutrition.

C-Reactive Protein↗
PubMed1997

Ring test for the determination of N-terminal valine adducts of styrene 7,8-oxide with haemoglobin by the modified Edman degradation technique.

A ring-test was organised between three laboratories using different versions of the modified Edman degradation technique for the gas chromatographic-mass spectrometric determination of N-terminal valine adducts of styrene 7,8-oxide. The analyses were performed on a sample of human haemoglobin reacted in vitro with styrene 7,8-oxide and on a set of five haemoglobin samples from mice dosed by i.p. injection of styrene. Strong correlations between the haemoglobin adduct determinations of the different laboratories were observed. However, covariance analysis revealed different slopes for the dose-response curves, indicating differences for the calibration of the reference globin or reference peptide.

Alkylation↗
PubMed1996

Monitoring human exposure to 2-hydroxyethylating carcinogens.

It is known that human hemoglobin contains low levels of N-terminal N-(2-hydroxyethyl)valine. Possible sources of this modified amino acid are exposure to ethylene oxide or other 2-hydroxy-ethylating agents. Although such processes are likely to occur endogenously, the exogenous contribution to the adduct formation is unclear. In order to explore the latter, we have analyzed N-(2-hydroxyethyl)valine in the globin of 49 pregnant women and evaluated the effect of smoking status, area of residence, and glutathione S-transferase M1 genotype on adduct levels. Transplacental transfer of hydroxyethylating agents was also studied by the analysis of umbilical cord hemoglobin. The adduct levels in smokers were significantly higher than those in nonsmokers. The adduct levels in umbilical cord blood globin were quantitatively related to those in maternal blood (maternal:fetal ratio 2.7 in smokers and 2.8 in nonsmokers). In the nonsmokers, there was no statistically significant difference in the adduct level between the urban and rural areas, but the level in suburbia tended to be lower than that in the rural area. In the combined smoker and nonsmoker groups, there was no effect of the glutathione S-transferase M1 genotype on levels of N-(2-hydroxyethyl)valine.

Adult↗
PubMed1996

Hepatic and erythrocytic glutathione peroxidase activity in liver diseases.

Hepatic and erythrocytic glutathione peroxidase activity, together with malondialdehyde levels, were determined as indicators of peroxidation in 83 patients from whom liver biopsies had been taken for diagnostic purposes. On histological study, the patients were classified into groups as minimal changes (including normal liver), steatosis, alcoholic hepatitis, hepatic cirrhosis, light to moderately active chronic hepatitis, and severe chronic active hepatitis. The glutathione peroxidase activity in erythrocytes showed no significant changes in any liver disease group. In the hepatic study, an increased activity was observed in steatosis with respect to the minimal changes group, this increased activity induced by the toxic agent in the initial stages of the alcoholic hepatic disease declining as the hepatic damage progressed. There was a negative correlation between the levels of hepatic malondialdehyde and hepatic glutathione peroxidase in subjects with minimal changes. This suggested the existence of an oxidative equilibrium in this group. This equilibrium is broken in the liver disease groups as was manifest in a positive correlation between malondialdehyde and glutathione peroxidase activity.

Erythrocytes↗
PubMed1996

[Serum levels of prealbumin in undernourished children and controls with or without associated clinical infection].

Due to its short half life and high tryptophan content, prealbumin has been considered a sensitive indicator of protein and/or energy deficiency. In addition, prealbumin diminishes during the acute phase response elicited by either infection or tissue injury. Serum levels of prealbumin were determined in undernourished children with or without associated clinical infection and in their infected or non-infected controls matched for age, sex, race and socioeconomical conditions. Serum levels of prealbumin were significantly lower in undernourished than in control children without overt infections. On the other hand, the concentrations of serum prealbumin diminished significantly and to similar levels both in undernourished and control children with associated clinical infection as compared with those observed in non infected children belonging to the similar nutritional status. A positive correlation was found between prealbumin level and the Z-scores of weight-for-age, height-for-age and weight-for height in children without associated infections, which disappeared in clinically infected patients. Thus, prealbumin is a marker of undernutrition in the absence of infection and could be an earlier and more sensitive indicator of actual undernutrition caused by the metabolic effects of acute phase cytokines, than the anthropometrical measurements used here.

Child, Preschool↗
PubMed1988

Metabolic characterization of isolated cerebral microvessels: ATP and ADP concentrations.

Isolated cerebral microvessels (ICMV) have been increasingly used to study microvascular metabolism and function. Despite this, little systematic information exists about their metabolic viability and energy status. To evaluate this, we determined the ATP content and ATP/ADP ratios of ICMV with an ultrasensitive bioluminometric assay which had been adapted for small samples. In calf cerebral microvessels, freshly isolated by a homogenization and sieving procedure, ATP content averaged 1.5 +/- 0.8 nmole/mg protein (mean +/- SE for 45 observations on 18 preparations.) The ATP/ADP ratio for these vessels was 0.96 +/- 0.4. Similar values for ATP were obtained in several preparations of ICMV from dog and rat brain. Values varied considerably in different preparations, probably due to variable degrees of damage incurred during isolation. When microvessel ATP concentrations and ATP/ADP ratios were low, they were dramatically improved by brief incubation (2 hr at 37 degrees) in an enriched tissue culture medium (Dulbecco's modification of Eagle's minimal essential medium, DMEM), or perhaps somewhat less effectively in a buffered saline solution (Earle's-Hepes) containing glucose. Boiling or incubation of microvessels with Triton X-100 lowered ATP values to less than 0.01 nmole/mg protein. The ATP content of our preparations of isolated microvessels was considerably higher than values previously reported by others using similar methods, but still less than that of cultured bovine vascular endothelial cells, even after correction for a 20% difference in intracellular water space.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1988

Effects of hypoglycemia and diabetes on fuel metabolism by rat brain microvessels.

Glucose and beta-hydroxybutyrate metabolism were compared in isolated cerebral microvessels from chronically diabetic and hypoglycemic rats. As noted previously, glucose oxidation and conversion to lactate are diminished in rats with streptozotocin-induced diabetes. The decrease in glucose metabolism did not result from selective damage to diabetic vessels during isolation, since the ATP level and the ATP/ADP ratio were similar to those of nondiabetic rats, and O2 consumption was increased. In addition, cerebral microvessel oxidation of beta-hydroxybutyrate was enhanced by diabetes. By contrast, microvessels from rats made chronically hypoglycemic by insulinoma engrafting 30 days earlier had a more than twofold increase in glucose oxidation and conversion to lactate, whereas their oxidation of beta-hydroxybutyrate was diminished by 50%. Unlike the insulinoma rats, no consistent increase in glucose metabolism was observed in microvessels from rats made hypoglycemic either by acute insulin administration or by a 4-day infusion of insulin. These results indicate that diabetes, and under some circumstances chronic hypoglycemia, markedly alters fuel metabolism in the cerebral microvasculature.

3-Hydroxybutyric Acid↗