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Biomedical subjects

J Segura

Publications and source records attributed to J Segura.

At least 127 records · Page 7Linked to original sources
PubMed1995

Systemic exposure to dietary heterocyclic amines in man.

2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-I-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are formed during the cooking of meat and account for a significant proportion of the mutagenic material present in cooked beef. The amines are not directly mutagenic but are converted to active intermediates by P450. Studies in vitro with human liver have shown that N-hydroxylation catalyzed by CYP1A2 is the major pathway of oxidation of MeQx and PhIP and is solely responsible for the generation of mutagenic species. In the studies reported in this paper it is demonstrated that both MelIQx and PhIP are well absorbed and extensively metabolized following ingestion of amine-containing beef by humans. Experiments with furafylline, a potent and selective inhibitor of human CYP1A2, reveal that more than 90% of MeIQx and 70% of PhIP are N-hydroxylated in vivo, probably presystemically in the liver.

Animals↗
PubMed1994

Simultaneous detection of methylphenidate and its main metabolite, ritalinic acid, in doping control.

Two analytical methods for the simultaneous detection in urine of methylphenidate and its main metabolite, ritalinic acid, are described. Both procedures are based on solid-phase extraction of urine samples on Bond Elut Certify columns, and capillary gas chromatographic-mass spectrometric detection of O-trimethylsilyl, N-trifluoroacetyl derivatives. The former method is used as a general screening procedure for the detection of basic polar nitrogen-containing compounds in urine such as stimulants, narcotic and adrenergic drugs. The latter procedure is proposed as a specific method to confirm methylphenidate ingestion. The two methods are sensitive enough to detect methylphenidate and ritalinic acid in urine at least for 24 h after administration of a therapeutic dose (20 mg oral dose) of methylphenidate.

Gas Chromatography-Mass Spectrometry↗
PubMed1994

CYP1A2-catalyzed conversion of dietary heterocyclic amines to their proximate carcinogens is their major route of metabolism in humans.

The contribution of CYP1A2 to the metabolism of the dietary heterocyclic amines, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in vivo in humans, has been determined with furafylline, a highly selective inhibitor of this enzyme. The inhibitory potential of furafylline in vivo was first assessed by determining its effect on clearance of phenacetin to paracetamol by the model CYP1A2-dependent O-deethylation pathway. Furafylline inhibited this reaction by > 99% in all subjects, thus demonstrating its applicability to determining the contribution of CYP1A2 to a given reaction in vivo. A group of 6 healthy male volunteers received either placebo or 125 mg furafylline, in a double-blind balanced crossover design, 2 h prior to consuming a test meal of fried beef containing a known amount of amines. The excretion of PhIP and MeIQx in urine was determined during the subsequent 28 h, using gas chromatography-mass spectrometry. Following furafylline, the excretion of unchanged MeIQx increased 14.3-fold, while that of PhIP increased 4.1-fold (P < 0.01, paired t test). Elimination of both amines was first order and very rapid, with half-lives of < 5 h. The elimination rate constants did not change following furafylline, suggesting that total clearance is limited by hepatic blood flow. Because the elimination of the amines was first order, it was possible to calculate the contribution of CYP1A2 to the clearance of the amines. CYP1A2-catalyzed metabolism accounts for 91% of the elimination of ingested MeIQx and 70% of ingested PhIP, most likely via N-hydroxylation.

Adult↗
PubMed1994

[An analysis of the factors and phenomena associated with the formation of a spontaneous echo contrast in the left atrium].

INTRODUCTION AND AIMS: To determine the factors related to the formation of spontaneous echo contrast in left atrium. PATIENTS AND METHODS: We have analyzed our series of 1,066 patients undergoing transesophageal echocardiography until December 1991. It was found in left atrium in 387 patients (36%) and was associated with another pathology in 99%. We defined spontaneous echo contrast as mild in 64% and severe in 36%. RESULTS: The prevalence of spontaneous echo contrast was greater in patients with atrial fibrillation (p < 0.001), mitral stenosis (p < 0.001), double mitral lesion (p < 0.001), prosthesis (p < 0.001), embolism (p < 0.05) and a dilated left atrium (left atrial dimension greater than 60 ml) (p < 0.01). The presence of mitral regurgitation made it less frequent (p < 0.05). Thrombi were visualized in 104 patients and they were more frequent in the presence of spontaneous echo contrast. Severe spontaneous echo contrast was significantly more frequent in patients with atrial fibrillation (p < 0.001), mitral stenosis (p < 0.05) and thrombi (p < 0.001). CONCLUSIONS: Spontaneous echo contrast in left atrium is a common finding in transesophageal studies and it is associated with another pathology in 99%. It is more frequent in patients with atrial fibrillation, mitral stenosis, embolism or prosthesis. Left atrial enlargement is one of the more important factors. It is less frequent in patients with mitral regurgitation. Thrombi are less frequent in patients without spontaneous echo contrast. Severe spontaneous echo contrast is significantly associated with mitral stenosis, atrial fibrillation and left atrial thrombi.

Acute Disease↗
PubMed1993

Alcohol and cocaine interactions in humans.

The effects of 100 mg of intranasal cocaine (COC) in acute alcohol intoxication (1 g/kg) was assessed in nine experienced and non-dependent healthy volunteers in a double-blind, controlled, randomized, cross-over clinical trial. Alcohol alone impaired psychomotor performance, whereas COC alone produced subjective effects related to euphoria and well-being, improved the reaction time and increased heart rate and blood pressure. The combination of COC and alcohol induced a nonsignificant decrease in the subjective feelings of drunkeness, an increase in COC-induced euphoria, a significant improvement in alcohol-related changes in psychomotor performance and a marked increase in heart rate. Subjects experienced subjective and performance effects that could be self-interpreted as more pleasant compared to the effects of alcohol alone. When alcohol was given simultaneously, COC plasma levels were higher (possibly as a result of an inhibition of hepatic metabolism of COC produced by alcohol), norcocaine plasma levels almost doubled and cocaethylene was detected in plasma, so that its basic pharmacokinetic profile could be described. The simultaneous use of both drugs produced changes in heart rate and blood pressure that could increase the risk of cardiovascular toxicity associated with the use of COC.

Adult↗
PubMed1993

International cooperation in analytical chemistry: experience of antidoping control at the XI Pan American Games.

We describe the experience of the international cooperation carried out for antidoping control at the XI Pan American Games. A temporary accreditation was granted by the International Olympic Committee to the accredited laboratory of Barcelona (Spain) to set up a Doping Control Laboratory in Havana. Two other laboratories from Mexico and Cuba contributed personnel, materials, and instrumentation. The main issues associated with the preparation and organization of the project are described. During 16 days, 741 urine samples were tested for stimulants, narcotics, anabolic steroids, beta-blockers, diuretics, cannabinoids, local anesthetics, and human chorionic gonadotropin by gas-liquid chromatography, gas chromatography/mass spectrometry, high-performance liquid chromatography, and immunoassay techniques. Analytical methodologies, quality-control strategies, and the main results are reported.

Acebutolol↗
PubMed1992

The pathogenesis of nodular regenerative hyperplasia of the liver associated with rheumatoid vasculitis.

Nodular regenerative hyperplasia (NRH) is an uncommon liver disease that typically develops in the setting of a chronic illness such as Felty's syndrome. Although the pathogenesis of NRH has not been defined, vasculitis has been postulated to play an important pathogenetic role in some cases of NRH, even though the association of NRH and vasculitis has been reported rarely. We describe two unusual cases of NRH in patients with Felty's syndrome complicated by rheumatoid vasculitis. Morphometric analysis demonstrated evidence of injury to the hepatic vasculature in the form of loss of small intrahepatic arteries and portal spaces, findings that support the hypothesis that hepatic arteritis plays a role in the development of NRH in cases associated with systemic vasculitis.

Adult↗
PubMed1992

[Bradyarrhythmias secondary to the use of ophthalmic timolol. A report of 3 cases].

Three cases of symptomatic bradycardia due to topical ocular timolol administration are reported. Two patients had syncope related to atrioventricular block, and the other one complained of dizziness due to sinus bradycardia. Heart disease was not present in any case, although a right bundle branch block was observed in one patients. A normal sinus rhythm resumed in all patients after discontinuation of timolol.

Aged↗
PubMed1991

Immediate and follow-up results of transluminal balloon dilation for discrete subaortic stenosis.

This study presents the findings in 33 patients with discrete subaortic stenosis who were treated by percutaneous balloon dilation and were followed up for 2 months to 6.2 years (mean 34 +/- 21 months). The mean age was 13 +/- 11 years; 10 (30%) were female and 23 (70%) male. Associated malformations were observed in nine patients (27%). All patients underwent noninvasive studies and cardiac catheterization. The mean value to membrane distance was 4.5 +/- 2 mm/m2. After balloon dilation, the pressure gradient from the left ventricle to the aorta decreased from 68 +/- 30 to 20 +/- 13 mm Hg (p less than 0.00001); there were no significant changes in the degree of aortic regurgitation. A fluttering and widely mobile remaining membrane was clearly visualized after dilation. Better immediate results were obtained in patients with a smaller baseline gradient, a larger aortic anulus and a longer valve to membrane distance. Serial follow-up echographic studies were available in 30 patients, and 18 hemodynamic reevaluations were performed in 13 patients. However, seven patients who demonstrated restenosis underwent redilation at a mean of 29 +/- 17 months after the first dilation. Redilation in six of the seven patients obtained benefits similar to those observed at the first dilation. Only one patient with unsuccessful redilation required surgery. The mean value of the last explored residual gradient (on hemodynamic or Doppler study) in the remaining 32 patients was 21 +/- 10 mm Hg. No significant changes were observed in the angiographic evolution of aortic regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Approach to the analysis of diuretics and masking agents by high-performance liquid chromatography-mass spectrometry in doping control.

The application of thermospray and plasmaspray high-performance liquid chromatography-mass spectrometry to the analysis of diuretics and probenecid has been investigated. The latter method gave better ionization efficiency than the former, and its response was optimized by altering the solvent composition: best results were obtained with water-methanol-acetonitrile-trifluoroacetic acid. Using different proportions of these solvents, three isocratic systems were developed to separate the compounds under study. The principal characteristic of plasmaspray positive-ion mass spectra was a protonated molecular ion and very little fragmentation was evident. In the negative ionization mode, the plasmaspray method gave mass spectra showing more fragmentation, which resulted in additional structural information. The ability of trifluoroacetic acid to form negative cluster ions precluded its use as a mobile phase component. The minimum detectable amounts determined by the analysis in the positive-ion mode was compound-dependent, but generally ca. 10-150 ng. In many cases the compounds could be detected in urine extracts.

Chromatography, High Pressure Liquid↗