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Biomedical subjects

M Duran

Publications and source records attributed to M Duran.

At least 37 records · Page 2Linked to original sources
PubMed2004

Fatty acids and homocysteine levels in patients with recurrent depression: an explorative pilot study.

Major depressive disorders (MDD) and cardiovascular disease are mutually associated. They share signs and symptoms of the "metabolic syndrome". Two observations that may be causally related with the metabolic syndrome and therefore with both MDD and cardiovascular disease are a decrease in omega-3 polyunsaturated fatty acids (PUFAs) and a rise in plasma homocysteine (tHcy) levels. Both the rise in tHcy and the decrease in omega-3 PUFAs may be associated with enhanced lipid peroxidation. We exploratively studied 44 randomly chosen patients out of a cohort of 134 patients with the recurrent form of MDD (MDD-R). We measured tHcy levels together with saturated FAs, monounsaturated fatty acids (MUFAs) and PUFAs of the omega-3, omega-6 and omega-9 series in plasma and erythrocytes. Levels were compared with laboratory reference values. The main findings were a decrease in the erythrocytes of C22:5omega-3, C22:6omega-3, C24:1omega-9 and C20:3omega-9 and in the plasma a decrease in C24:1omega-9 and C20:3omega-9. The only significant association we found was between the total of omega-6 fatty acids and plasma tHcy. The FA alterations were found in patients although most of them were clinically recovered, suggesting that the alterations may represent a biological" trait" marker for recurrent depression.

Adult↗
PubMed2004

Co-digestion with waste activated sludge for improved methanogenesis from high solids industrial waste.

The objective of this work was to study the anaerobic digestion of an industrial waste with 84% total and 57% volatile solids content. The waste was also characterized by high total COD content, 42% by weight. The anaerobic digestion of the waste alone and its co-digestion with the waste activated sludge (WAS) that is generated at the industrial facility were investigated. Particularly, kinetics of digesting the waste alone and co-digesting it with the WAS were determined. The substrate utilization rates under varying initial substrate concentrations were determined in batch reactors by measuring the methane generation rates. Then the substrate utilization rates were modeled according to the Monod kinetics. The solution to nonlinear regression resulted in the maximum specific substrate utilization rates (k) of 0.138 and 0.165 g COD g VSS(-1).day(-1) for the waste alone and the waste co-digested with the WAS, respectively. The half velocity constants (K s) were 4.390 and 4.860 g COD 1(-1) for the same conditions. It is important to note that since the methane generation data were used to determine the substrate utilization rates, these kinetic constants are likely to represent the methanogenic Archaea rather than the entire anaerobic consortium. It is concluded that the anaerobic co-digestion of this industrial waste with the WAS is beneficial from the digestion kinetics point of view since the k increased approximately 20% with the addition of the WAS. Moreover, there will be cost savings associated with digesting the WAS anaerobically rather than aerobically, the currently used method of WAS management, if anaerobic digestion is adopted in the future.

Bacteria, Anaerobic↗
PubMed2004

Changes in blood carnitine and acylcarnitine profiles of very long-chain acyl-CoA dehydrogenase-deficient mice subjected to stress.

BACKGROUND: In humans with deficiency of the very long-chain acyl-CoA dehydrogenase (VLCAD), C14-C18 acylcarnitines accumulate. In this paper we have used the VLCAD knockout mouse as a model to study changes in blood carnitine and acylcarnitine profiles under stress. DESIGN: VLCAD knockout mice exhibit stress-induced hypoglycaemia and skeletal myopathy; symptoms resembling human VLCADD. To study the extent of biochemical derangement in response to different stressors, we determined blood carnitine and acylcarnitine profiles after exercise on a treadmill, fasting, or exposure to cold. RESULTS: Even in a nonstressed, well-fed state, knockout mice presented twofold higher C14-C18 acylcarnitines and a lower free carnitine of 72% as compared to wild-type littermates. After 1 h of intense exercise, the C14-C18 acylcarnitines in blood significantly increased, but free carnitine remained unchanged. After 8 h of fasting at 4 degrees C, the long-chain acylcarnitines were elevated 5-fold in knockout mice in comparison with concentrations in unstressed wild-type mice (P < 0.05), and four out of 12 knockout mice died. Free carnitine decreased to 44% as compared with unstressed wild-type mice. An increase in C14-C18 acylcarnitines and a decrease of free carnitine were also observed in fasted heterozygous and wild-type mice. CONCLUSIONS: Long-chain acylcarnitines in blood increase in knockout mice in response to different stressors and concentrations correlate with the clinical condition. A decrease in blood free carnitine in response to severe stress is observed in knockout mice but also in wild-type littermates. Monitoring blood acylcarnitine profiles in response to different stressors may allow systematic analysis of therapeutic interventions in VLCAD knockout mice.

Acyl-CoA Dehydrogenase, Long-Chain↗
PubMed2003

Partial response to biotin therapy in a patient with holocarboxylase synthetase deficiency: clinical, biochemical, and molecular genetic aspects.

We report the clinical course and biochemical findings of a 10-year-old, mentally retarded girl with late-onset holocarboxylase synthetase (HCS, gene symbol HLCS) deficiency and only partial response to biotin. On treatment, even with an unusually high dose of 200mg/day, activities of the biotin-dependent mitochondrial carboxylases in lymphocytes remained below 50% of the mean control values. Not only urinary 3-hydroxyisovaleric acid excretion has been persistently elevated, but also plasma and, with even higher concentrations, cerebrospinal fluid 3-hydroxyisovaleric acid have not normalized. The unusual and insufficient response of this patient to biotin treatment can be explained by the effect of the combination of the common HLCS allele IVS10 +5 g>a on one chromosome and a truncating mutation on the other. This case illustrates mechanisms involved in the genotype-phenotype correlation that unequivocally exists in HCS deficiency.

Age of Onset↗
PubMed2003

The eye as a window to inborn errors of metabolism.

Ocular manifestations in inborn errors of metabolism occur in many diseases and may be associated with any part of all eye components. In a minority of diseases it is possible to attribute the eye symptoms to a single hereditary pathogenetic mechanism. More often the aetiological relationship of the ocular defects to the metabolic disease is unknown. Diverse pathogenetic mechanisms may act via a common pathological pathway inducing ocular damage. The occurrence of eye abnormalities in metabolic disorders suggests that they are associated with direct toxic actions, errors of synthetic pathways or deficient energy metabolism. In this review, metabolic disorders with major abnormalities in the cornea, lens, retina and optic nerve are presented. In all cases, an appropriate combined approach by the ophthalmologist, paediatrician/neurologist, geneticist and clinical biochemist is the only way to diagnostic success.

Animals↗
PubMed2003

High activity of fatty acid oxidation enzymes in human placenta: implications for fetal-maternal disease.

As the human fetus and placenta are considered to be primarily dependent on glucose oxidation for energy metabolism, the cause of the remarkable association between severe maternal pregnancy complications and the carriage of a fetus with an inborn error of mitochondrial long-chain fatty acid oxidation (FAO) has remained obscure. We analysed human term placenta and chorionic villus samples for the activities of a variety of enzymes involved in FAO, and compared the results with those obtained in human liver. All enzymes were found to be expressed, with a very high activity of two enzymes involved in the metabolism of long-chain fatty acids (CPT2 and VLCAD), whereas the activity of medium-chain acyl-CoA dehydrogenase (MCAD) was found to be low, when compared to liver. These results suggest that fatty acid oxidation may play an important role in energy generation in human placenta, and that a deficiency in the placental oxidation of long-chain FAO may result in placental dysfunction, thus causing gestational complications.

Acyl-CoA Dehydrogenase↗
PubMed2003

Silent and symptomatic primary carnitine deficiency within the same family due to identical mutations in the organic cation/carnitine transporter OCTN2.

A family of Turkish origin with primary systemic carnitine deficiency in the father and his two sons is described. In all three individuals, the same homozygous mutation in the OCTN2 gene (R471H) was present and carnitine uptake in fibroblasts was deficient. Whereas one boy became symptomatic with a Reye-syndrome-like picture of hepatopathy and encephalopathy in infancy, the other affected family members remained asymptomatic up to their current ages of 28 and 5 years, respectively.

Adult↗
PubMed2003

Mutations in SRD5B1 (AKR1D1), the gene encoding delta(4)-3-oxosteroid 5beta-reductase, in hepatitis and liver failure in infancy.

BACKGROUND: A substantial group of patients with cholestatic liver disease in infancy excrete, as the major urinary bile acids, the glycine and taurine conjugates of 7alpha-hydroxy-3-oxo-4-cholenoic acid and 7alpha,12alpha-dihydroxy-3-oxo-4-cholenoic acid. It has been proposed that some (but not all) of these have mutations in the gene encoding delta(4)-3-oxosteroid 5beta-reductase (SRD5B1; AKR1D1, OMIM 604741). AIMS: Our aim was to identify mutations in the SRD5B1 gene in patients in whom chenodeoxycholic acid and cholic acid were absent or present at low concentrations in plasma and urine, as these seemed strong candidates for genetic 5beta-reductase deficiency. PATIENTS AND SUBJECTS: We studied three patients with neonatal onset cholestatic liver disease and normal gamma-glutamyl transpeptidase in whom 3-oxo-delta(4) bile acids were the major bile acids in urine and plasma and saturated bile acids were at low concentration or undetectable. Any base changes detected in SRD5B1 were sought in the parents and siblings and in 50 ethnically matched control subjects. METHODS: DNA was extracted from blood and the nine exons of SRD5B1 were amplified and sequenced. Restriction enzymes were used to screen the DNA of parents, siblings, and controls. RESULTS: Mutations in the SRD5B1 gene were identified in all three children. Patient MS was homozygous for a missense mutation (662 C>T) causing a Pro198Leu amino acid substitution; patient BH was homozygous for a single base deletion (511 delT) causing a frame shift and a premature stop codon in exon 5; and patient RM was homozygous for a missense mutation (385 C>T) causing a Leu106Phe amino acid substitution. All had liver biopsies showing a giant cell hepatitis; in two, prominent extramedullary haemopoiesis was noted. MS was cured by treatment with chenodeoxycholic acid and cholic acid; BH showed initial improvement but then deteriorated and required liver transplantation; RM had advanced liver disease when treatment was started and also progressed to liver failure. CONCLUSIONS: Analysis of blood samples for SRD5B1 mutations can be used to diagnose genetic 5beta-reductase deficiency and distinguish these patients from those who have another cause of 3-oxo-delta(4) bile aciduria, for example, severe liver damage. Patients with genetic 5beta-reductase deficiency may respond well to treatment with chenodeoxycholic acid and cholic acid if liver disease is not too advanced.

Chenodeoxycholic Acid↗
PubMed2002

Cerebral arteriovenous malformations: morphologic evaluation by ultrashort 3D gadolinium-enhanced MR angiography.

The purpose of this study was to evaluate the usefulness of a new ultrashort contrast-enhanced (CE) MR angiography (MRA) for the morphologic evaluation of cerebral arteriovenous malformations (AVMs). The method was compared with conventional X-ray digital subtraction angiography (DSA) and time-of-flight (TOF) MRA in 22 patients to assess the angioarchitecture of the malformations which is essential for treatment planning and follow-up. Two experienced MR readers independently evaluated both techniques with regard to the assessment of feeding arteries, AVM nidus, and venous drainage patterns. Contrast-enhanced MRA was able to detect all AVMs seen on DSA, whereas the TOF MRA failed in 1 patient with a very small AVM. In the assessment of the different vessel components of the AVM there was no difference for the detection and delineation of feeding arteries and the AVM. The venous drainage patterns could always be clearly delineated in the CE MRA, whereas TOF MRA could demonstrate the exact venous drainage in only 9 patients. Contrast-enhanced MRA was found to be superior to conventional TOF MRA in the assessment of the angioarchitecture of cerebral AVMs especially regarding the assessment of the venous drainage patterns. The superiority is supported by the improved vessel-to-background contrast and contrast-to-noise ratios. The major limitations of this new technique consist of a low spatial resolution at the used time resolution which can be improved by further sequence modifications. Contrast-enhanced MRA is thus an important additional imaging technique for treatment planning and follow-up of AVMs.

Adult↗
PubMed2002

Congenital microcephaly and seizures due to 3-phosphoglycerate dehydrogenase deficiency: outcome of treatment with amino acids.

Congenital microcephaly, intractable seizures and severe psychomotor retardation characterize 3-phosphoglycerate dehydrogenase (3-PGDH) deficiency, a disorder of L-serine biosynthesis. The enzyme defect results in low concentrations of serine and to a variable degree of glycine in plasma and cerebrospinal fluid. Short-term beneficial effects have been reported of oral treatment with the deficient amino acids. In this paper, we report the first follow-up data of amino acid therapy in five patients treated for 3-7.5 years. Different treatment regimes were used, but a favourable response to amino acids was observed in all patients. A major reduction in seizure frequency occurred in all patients; two patients became free of seizures. Amino acids were well tolerated and no adverse effects were documented. A progress of psychomotor development was only observed in one patient, diagnosed early and treated with a high dosage of L-serine. A favourable outcome of 3-PGDH deficiency depends on early diagnosis and treatment.

Carbohydrate Dehydrogenases↗
PubMed2002

Efficacy and safety of a phytoestrogen preparation derived from Glycine max (L.) Merr in climacteric symptomatology: a multicentric, open, prospective and non-randomized trial.

A multicentric, open, prospective, observational and no-randomized clinical trial was carried out in Spain with 190 postmenopausal women receiving a soy preparation rich in isoflavones (PHYTO SOYA, capsules containing 17.5 mg isoflavones). The main object of the present study was to investigate its efficacy in alleviating the symptomatology derived from the lack of estrogen, mainly hot flushes, but also other symptoms such as sleep disorder, anxiety, depression, vaginal dryness, loss of libido and bone pain. Each patient received 35 mg isoflavones per day in two doses. During the four months' treatment, a statistically significant decrease in the number of hot flushes with PHYTO SOYA was experienced by 80.82% women; only 5,48% patients did not improve with the treatment. The average reduction was 47.8%, which is equivalent to 4 hot flushes. All the other studied parameters also showed a statistically significant decrease. No severe side-effects were reported and tolerance was excellent. Treatment with PHYTO SOYA resulted in a significant improvement of the symptomatology that accompanies the lack of estrogen during menopause.

Anxiety↗
PubMed2001

Differential effect of valproate and its Delta2- and Delta4-unsaturated metabolites, on the beta-oxidation rate of long-chain and medium-chain fatty acids.

Overall fatty acid oxidation rates were investigated in rat hepatocytes using [9,10-3H]-palmitic, [9,10-3H]-oleic, [9,10-3H]-myristic and [2,3-3H]-phenylpropionic acids. The effect of both valproate (VPA) (0-10 mM) and two of its unsaturated metabolites, Delta2(E)-VPA and Delta4-VPA (0-10 mM), on the overall 3H2O production rate was studied. The results give evidence of a general inhibitory effect of VPA on the beta-oxidation rate of all the tested substrates. Similar effects were observed with both VPA metabolites but these effects appeared to be dependent on the chain length of the substrate. When the effect on the oxidation of the medium-chain fatty acid 3-phenylpropionate (PPA) was studied, Delta2(E)-VPA at 0.5 mM caused a 94% inhibition of the overall beta-oxidation rate. However, with long-chain substrates, 0.5 mM Delta(4)-VPA was a more potent inhibitor (20-30% of control activity) than 0.5 mM Delta(2E)-VPA (60-80% of control activity). Our results suggest that VPA and/or its metabolites inhibit fatty acyl-CoA metabolism within the mitochondrion by two different mechanisms. The first mechanism involves CoASH sequestration, which affects the oxidation rate of all fatty acids with different chain length. The second mechanism is more specific in nature and involves selective inhibition of particular enzymes implicated in fatty acid beta-oxidation.

Animals↗
PubMed2001

Synthesis and intramitochondrial levels of valproyl-coenzyme A metabolites.

A number of valproate adverse reactions are due to its interference with several metabolic pathways, including that of fatty acid oxidation. In order to resolve which mitochondrial enzymes of fatty acid oxidation are inhibited by which VPA intermediates we have developed methods to synthesize their CoA ester forms. This paper describes the synthesis of VPA acyl-CoA ester metabolites as well as data on the fate of VPA in rat liver mitochondria. Valproyl-CoA, Delta2-valproyl-CoA, and 3-OH-valproyl-CoA were obtained through chemical synthesis. 3-Keto-valproyl-CoA was prepared by a novel enzymatic procedure followed by a combination of solid-phase extraction and preparative HPLC purification. This approach proved to be efficient in obtaining all the beta-oxidation intermediates of valproyl-CoA. The synthetic standards were used for the determination of intramitochondrial concentrations of valproyl-CoA, Delta2-valproyl-CoA, 3-OH-valproyl-CoA, and 3-keto-valproyl-CoA by HPLC. These levels were determined after incubation of intact rat liver mitochondria with VPA under conditions of state 3 and state 4 respiration. The results show that valproyl-CoA and to a much lesser extent 3-keto-valproyl-CoA are the main metabolites of VPA in mitochondria. This information will be of great use in resolving the mechanisms involved in the inhibition of mitochondrial processes like fatty acid oxidation by VPA.

Acyl Coenzyme A↗