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Biomedical subjects

M Duran

Publications and source records attributed to M Duran.

At least 145 records · Page 8Linked to original sources
PubMed1996

Magnetic resonance imaging and spectroscopy of the brain in propionic acidemia: clinical and biochemical considerations.

Three patients with propionic acidemia were studied. The first patient was diagnosed at the age of 9 mo, 3 mo after he developed hypotonia and choreoathetoid movements after an upper respiratory tract infection. The second patient was diagnosed at the age of 1.5 mo when she became comatose after nasogastric tube feeding because of failure to thrive. The third patient was diagnosed at the age of 5 d when she presented with feeding difficulties, hypotonia, and respiratory insufficiency. Magnetic resonance imaging (MRI) of the brain in all patients revealed delayed myelination and some cerebral atrophy. In the patient with choreoathetosis, MRI showed bilateral abnormalities in the signal intensity of the putamen and caudate nuclei. MRI of the other two patients showed normal basal ganglia. Proton magnetic resonance spectroscopy (1H MRS) from a voxel located in the basal ganglia revealed a decrease in N-acetylaspartate and myo-inositol peaks and an elevation of glutamine/ glutamate. The presence of spectroscopic abnormalities in a stable metabolic condition, in particular the rise in glutamine/ glutamate, indicates that the metabolic balance on cerebral parenchymal level is less optimal than estimated from biochemical analysis of urine, plasma, or cerebrospinal fluid.

Age of Onset↗
PubMed1996

Effects of progestogen on lipids, lipoproteins and apolipoproteins during transdermal estrogen replacement therapy with and without medroxyprogesterone acetate.

OBJECTIVE: To assess whether the effects on plasma lipids and lipoproteins after oophorectomy differ in patients who receive transdermal estrogen replacement therapy (ERT) with and without progestin. STUDY DESIGN: Twenty-five healthy, normal-weight, regularly menstruating women who underwent hysterectomy and bilateral oophorectomy for benign diseases received, for one year, transdermal therapeutic systems containing estradiol with daily delivery of 50 micrograms cyclically for 24 days per month plus 2.5 mg/d of oral medroxyprogesterone acetate (MPA) sequentially for the last 12 days of each cycle. After the first year the patients ceased to take MPA. We determined the levels of cholesterol (CHOL), high density lipoprotein (HDL)-CHOL, low density lipoprotein (LDL)-CHOL, triglycerides (TG) and apolipoproteins (apo) A-I and B prior to oophorectomy, one month after surgery and during the 6th and 12th months on estrogen plus progestogen substitution and during the 18th and 24th months without progestogen addition. RESULTS: After oophorectomy, the patients showed increases in LDL, apo-B and atherogenic index, whereas after hormone replacement therapy the patients exhibited falls in plasma LDL, apo-B and atherogenic index and increases in HDL and apo A-I. No significant changes in total CHOL were observed after surgery or treatment, and TG were decreased. Plasma levels of lipids and lipoproteins during estrogen replacement therapy (ERT) without MPA were not significantly different from those observed during ERT plus MPA. CONCLUSION: Changes in lipids induced by transdermal ERT were not affected by low doses of MPA.

Administration, Cutaneous↗
PubMed1996

Aberrantly spliced mRNAs of the 3-hydroxy-3-methylglutaryl coenzyme A lyase (HL) gene with a donor splice-site point mutation produce hereditary HL deficiency.

A novel point mutation in the 3-hydroxy-3methyl-glutaryl coenzyme A lyase gene was found in a Turkish patient with homozygous 3-hydroxy-3-methylglutaric acidemia. Amplification by RT-PCR of the mRNA using a six different pairs of oligonucleotides produced no differences in four of the fragments amplified with respect to the control, but generated two fragments of different size. One was representative of a deletion of 126 bp and the other of an insertion of 78 bp. These abnormal mRNAs resulted from a G-->C transversion at the nucleotide +1 of an intron, which changed the invariant GT dinucleotide of the 5' donor splice site. This was associated with the occurrence of an alternative splicing, which led to the skipping of the whole exon of 126 bp, and also with the activation of one cryptic donor splice site in the same intron. These aberrant spliced mRNAs are predicted to encode two abnormal HMG-CoA lyase proteins: the first results in a protein with an internal deletion of 42 amino acids, whose enzyme activity is largely abolished, as the catalytic site was completely removed; the second contains 17 missense amino acids that precede a stop codon. Northern blot analysis showed that the overall content of these aberrantly spliced mRNAs in proband fibroblasts was the same as that found in control fibroblasts. However, hardly any transcript was observed corresponding to the inserted mutated mRNA when it was examined by a specific probe. To quantify the relative proportion of the two mRNAs, a quantitative RT-PCR (the DNA-mimic PCR reaction) was carried out. Results show that the proportion of the inserted mRNAs with respect to the deleted mRNA is only 1.2%. The father, mother, and two brothers of the proband were heterozygous in the G-->C mutation in the +1 nucleotide of the intron considered, while the two alleles of another brother were free of the mutation.

Base Sequence↗
PubMed1995

Lymphatic regulation of hematocrit during hypoxia in the toad Bufo woodhousei.

Hypoxia rapidly increases hematocrit (Hct) in anuran amphibians by reducing plasma volume, but the mechanism(s) mediating this response is unknown. We tested the hypothesis that, during hypoxia, plasma volume is reduced by impaired lymph heart (LH) function, decreasing lymph flow into the circulation. In Bufo woodhousei, we measured the effects of hypoxia on Hct, lymph heart rate (LHR), LH pressure, the movement of dye from the dorsal lymph sac to the arterial blood, and flow through an open LH cannula. We also tested whether splenic contraction or cholinergic nerves contribute to the hypoxia-induced changes. Graded hypoxia between 21 and 4% O2 produced graded increases in Hct (P < 0.0001) and decreases in LHR (P = 0.01). Hypoxia reduced the rate of increase in arterial Evans blue concentration after injection into the dorsal lymph sac (P = 0.041) and decreased flow through an open LH cannula (P < 0.012). Hypoxia increased Hct and reduced LHR similarly in control, splenectomized, and sham-splenectomized toads. Atropine had no significant effect on Hct and LHR. These results indicate that the LHs play a regulatory role in hypoxia-induced hemoconcentration.

Animals↗
PubMed1995

D-2-hydroxyglutaric aciduria.

Hydroxyglutaric aciduria is detected by gas chromatographic-mass spectrometric analysis, and the D and L forms are quantified by chemical ionization with deuterated internal standards. Patients have recently been described who accumulate the D form, and they appear to be quite different from those with the more common L form. Experience is reported with three patients and an animal model with D-2-hydroxyglutaric aciduria. The phenotype appears to include mental retardation, macrocephaly, hypotonia, seizures, and involuntary movements, although neurologic and systemic manifestations of the disorder varied considerably between individual patients, even within the same family.

Animals↗
PubMed1995

Trial of routine gonadotropin releasing hormone agonist treatment before abdominal hysterectomy for leiomyoma.

OBJECTIVE: To investigate the usefulness of a routine short term treatment with gonadotropin releasing hormone agonist (D-Trp-6-LHRH depot) before abdominal hysterectomy for leiomyoma. STUDY DESIGN: Prospective, comparative, randomized study. SETTING: A teaching hospital of Barcelona University. PATIENTS: Fifty premenopausal women requiring hysterectomy as treatment for symptomatic leiomyomas. Twenty-three patients were randomized to receive gonadotropin releasing hormone agonist treatment before hysterectomy (cases), and 27 patients were randomized to immediate hysterectomy (controls). MAIN OUTCOME MEASURES: Type of abdominal incision, operating time, operative hemoglobin and hematocrit decrease, postoperative morbidity, and days in hospital. RESULTS: In the agonist treated group mean uterine volume decreased and mean hemoglobin and hematocrit significantly rose after 8 weeks of treatment. Operative time was similar in both groups of patients but the number of women having Pfannenstiel incision was significantly higher in the cases. Mean operative hemoglobin and hematocrit decrease and postoperative morbidity were lower in the cases. There was a trend for shorter postoperative hospital stays in the agonist treated group. CONCLUSIONS: Our results favor the routine use of a short term gonadotropin releasing hormone agonist treatment before abdominal hysterectomy for leiomyoma in order to decrease operative blood loss and postoperative morbidity.

Adult↗
PubMed1994

Urinary excretion of homocitric acid and methylhomocitric acid in propionic acidaemia: minor metabolic products of the citrate synthase aldol condensation reaction.

The identity of two formerly novel citric acid analogues, homocitric acid and methylhomocitric acid, in urine samples from patients with propionic acidaemia was confirmed by gas chromatography and mass spectrometry. Authentic reference substances were synthesized using a Reformatskii reaction. Homocitric acid and methylhomocitric acid were detected as minor metabolites in the urine samples from propionyl coenzyme A carboxylase deficient individuals. It was shown that these substances can be formed by the citrate synthase condensation reaction of alpha-ketoglutarate with acetyl coenzyme A and propionyl coenzyme A, respectively.

Acidosis↗
PubMed1994

Identification of the stereoisomeric configurations of methylcitric acid produced by si-citrate synthase and methylcitrate synthase using capillary gas chromatography-mass spectrometry.

The absolute separation of the four stereoisomeric configurations of methylcitric acid can be achieved on a nonchiral stationary phase SE30 capillary column using the corresponding O-acetylated (tri-(-)-2-butyl ester derivatives. Identification of the separated isomers was done using methylcitric acid produced by si-citrate synthase and methylcitrate synthase of Candida lipolitica. si-Citrate synthase produces the (2S,3S)-, (2S,3R)- and a small amount of the (2R,3S)-isomers. Methylcitrate synthase produces the (2R,3S)-isomer, indicating that this enzyme is more stereospecific than the animal citrate synthase enzyme. The (2R,3R)-isomer may act as an inhibitor of aconitase.

Citrate (si)-Synthase↗
PubMed1994

Amino acid and carnitine supplementation in haemodialysed children.

Plasma carnitine, amino acids and lipids levels were studied in ten uraemic children treated with haemodialysis and given amino acid supplementation with and without carnitine. As carnitine is synthesised from lysine and methionine and has a significant influence on lipid metabolism, the relationship between these was examined. Amino acid supplementation (0.25 g/kg body weight) was started with the intention of improving the plasma amino acid pattern in these children and increasing the concentration of lysine, which is the substrate for carnitine synthesis. Amino acids were administered i.v. during dialysis and carnitine (25 mg/kg body weight i.v.) was administered after dialysis three times a week. Concentrations of most essential amino acids were decreased in these patients. The first period of amino acid supplementation did not increase plasma levels of the essential amino acids, with the exception of tyrosine (P < 0.01). After the second period of supplementation, methionine was increased (P < 0.01), isoleucine was decreased (P < 0.01), but tyrosine normalised and was significantly lower than after the first period (P < 0.05). Thus overall amino acid supplementation did not improve amino acid levels; it was inconsistently associated with a further decrease in high-density lipoprotein-cholesterol and an increase in total protein levels. Lysine concentrations after amino acid supplementation remained low. Paradoxically, before carnitine supplementation a positive correlation between free carnitine and triglycerides was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Rett syndrome in a patient with medium chain acyl-CoA dehydrogenase deficiency.

A female patient with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency developed normally until 13 months of age after which she showed a gradual developmental delay, followed by progressive dementia, and a decrease in head circumference growth culminating in the diagnosis of Rett syndrome at 3.5 years.

Acyl-CoA Dehydrogenase↗
PubMed1994

Group tests for selective screening of inborn errors of metabolism.

Selective screening for inherited metabolic disorders can be performed efficiently by chromatographic techniques. Each technique is suited for a well-defined group of substances present in urine, plasma and CSF. A comprehensive screening programme may involve the analysis of amino acids, organic acids, imidazoles, purines and pyrimidines, oligosaccharides and mucopolysaccharides in urine as well as very long-chain fatty acids in plasma. The experienced laboratory, in close co-operation with a specialized paediatrician, will make a positive diagnosis in 6% of the referred samples, provided a careful selection of the patients is made. Our experience of 10 years of screening revealed 100 different defects; 30% of these were so-called amino acid disorders, 50% organic acidurias and the remaining 20% miscellaneous defects. Chromatographic methods are well suited for the discovery of novel defects. In this respect group screening tests will remain of major importance for the study of inborn errors of metabolism.

Chromatography↗
PubMed1994

Selective screening for amino acid disorders.

The analysis of amino acids is the most frequently applied technique in the selective screening of inborn errors of metabolism. When urine is used as a starting material, simple techniques such as thin-layer chromatography or high-voltage electrophoresis is preferred as a first approach. The quantitative analysis requires instrumentation, usually an amino acid analyser. Both plasma and urine are needed for establishing renal transport defects. Apart from the accumulation of the 'usual' amino acids, the presence of unusual amino acids may be of diagnostic significance. Furthermore the finding of decreased plasma concentrations of specific amino acids may pinpoint several inherited defects. No amino acid screening procedure is complete without the availability of an organic acid and a purine/pyrimidine analytical system, both yielding important additional diagnostic information. Considerable clinical problems may occur in subjects with a decreased tolerance to protein amino acids without being homozygous for any inherited defect. Examples of these disorders that need further studies are homocysteinaemia associated with vascular disease and carriers of ornithine transcarbamylase deficiency.

Amino Acid Metabolism, Inborn Errors↗
PubMed1994

Serotonin, a potent modulator of arachidonic acid turnover, interaction with glutamatergic receptor in brain cortex.

Brain cortex synaptoneurosomes actively incorporated [14C]arachidonic acid (AA) into lipids. Serotonin (5-HT), at a concentration range of 10 microM-1 mM, significantly stimulates the incorporation of AA mainly into phosphatidylinositol (PI) of brain cortex synaptoneurosomes. The stimulation rate of AA incorporation by 5-HT was the same in the presence and absence of lysophosphatidylinositol (LPI). However, in the absence of LPI some stimulation of AA uptake was also observed into phosphatidylcholine, phosphatidylethanolamine and phosphatidic acid. Buspirone, an agonist of 5-HT1A receptor, has a similar effect on AA incorporation into membrane lipids as serotonin itself. Moreover, ketanserin, an antagonist of 5-HT2 receptor, also induces activation of AA incorporation into membrane lipids. On the other hand, glutamate, in a concentration dependent manner, significantly inhibits AA uptake into PI and also has some inhibitory action on AA uptake into the other lipids. Serotonin itself and the agonist of 5-HT1A receptor through the activation of AA turnover counteract glutamate-induced inhibition of AA uptake into lipids of brain cortex. Our results indicated that serotonin directly, through the specific receptors, or indirectly, through the interaction with glutamatergic receptors, modulates turnover and the level of arachidonic acid in the brain.

Animals↗
PubMed1994

Aging diminishes serotonin-stimulated arachidonic acid uptake and cholinergic receptor-activated arachidonic acid release in rat brain cortex membrane.

Synaptoneurosomal and synaptosomal fractions from the brain cortex of adult (4-month-old) and aged (27-month-old) rats were used for studies on the uptake and subsequent release of [14C]arachidonic acid ([14C]AA) from brain lipids. The incorporation of AA and the pattern of its uptake into lipids of the aged brain cortex synaptoneurosomes and synaptosomes were not significantly different when compared with those in the adult brain cortex fractions. Serotonin (5-HT), at 10 microM to 1 mM in the presence of pargyline and the agonist of the 5-HT1A receptor, buspirone, stimulated AA uptake into membrane lipids, mainly into phosphatidylinositol, by about 40% exclusively in adult brain synaptoneurosomes. Aging significantly diminished the effect of 5-HT on AA uptake. Synaptoneurosomal and synaptosomal fractions prelabeled with [14C]AA were used subsequently for investigation of voltage-dependent, muscarinic and 5-HT receptor-mediated AA release. Aging diminished markedly carbachol-stimulated Ca(2+)-dependent AA liberation from membrane lipids of synaptoneurosomes and synaptosomes. Moreover, aging decreased voltage-dependent and 5-HT2 receptor-mediated AA release. These results show that aging affects receptor-dependent AA uptake and pre- and postsynaptic receptor-mediated AA release. These modulations of AA incorporation and release in aged brain may be of pathophysiological significance, in view of the importance of these processes for signal transmission in the brain. The changes of receptor-dependent processes of deacylation and reacylation may be responsible for alteration in the function of neuronal cells and may affect learning and memory ability and brain plasticity during aging.

Aging↗
PubMed1994

Rate-dependent distal renal tubular acidosis and carnitine palmitoyltransferase I deficiency.

An infant girl presented with recurrent episodes of Reye-like syndrome associated with hypoketosis and plasma carnitine levels in the high-normal range. A liver biopsy revealed massive macrovesicular steatosis. Ketogenesis was absent after a long-chain triglyceride loading test; in contrast, the medium-chain triglyceride loading test resulted in a brisk rise in plasma ketone concentration. Carnitine palmitoyltransferase I deficiency was demonstrated in cultured skin fibroblasts. Hypoglycemia was only found once in the neonatal period. Renal carnitine handling was normal except for a higher renal threshold for free carnitine. Mild, persistent metabolic acidosis was a constant feature, even during periods between metabolic decompensation. Evaluation of the renal acidification capacity showed a failure to acidify the urine during spontaneous acidosis but increased acid excretion and a normal decrease of urinary pH after acid loading. Also, a small difference between urine and blood PCO2 was found after bicarbonate administration. This acidification defect can best be explained as an abnormality in distal tubular H+ secretion: a rate-dependent distal tubular acidosis.off is speculated that long-chain acylcarnitines, substances that cannot be formed by carnitine palmitoyltransferase I-deficient patients, play an essential role in renal acid-base homeostasis.

Acidosis, Renal Tubular↗