Biomedical subjects
Publications and source records attributed to J Arenas.
We studied a pateint whose clinical, morphological and biochemical findings were consistent with McArdle's disease. Molecular genetic studies revealed that the patient did not harbor the common Arg49Stop mutation and was homozygous for the Gly204Ser mutation. Until now, no patient having the missense mutation in the two alleles has been documented.
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To elucidate the possible role of carotenoids and vitamin A as risk factors for Alzheimer's disease (AD), we compared serum levels of beta-carotene and alpha-carotene, and vitamin A, measured by isocratic high performance liquid chromatography, of 38 AD patients and 42 controls. The serum levels of alpha-carotene did not differ significantly between AD patients and control groups. However, the serum levels of beta-carotene and vitamin A were significantly lower in the AD-patient group. These values did not correlate to age, age at onset or score on the MiniMental State Examination. Weight and body mass index were significantly lower in AD patients than in controls. These results suggest that low serum beta-carotene concentrations in AD patients could be related to a deficiency in dietary intake of this provitamin, although its possible relationship with risk for AD could not be excluded.
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To elucidate whether serum alpha and beta-carotene and retinol levels are related with the risk for amyotrophic lateral sclerosis (ALS), we compared serum levels of alpha-carotene, beta-carotene, and retinol (vitamin A), measured by HPLC, in 40 patients with amyotrophic lateral sclerosis (ALS) and 87 matched controls using an isocratic high performance liquid chromatography technique. The mean serum alpha and beta-carotene, and retinol levels did not differ significantly between the 2 study groups. These values were not influenced by the clinical form (spinal vs bulbar) of ALS, and they did not correlate with age, age at onset, and duration of the disease. These results suggest that serum alpha and beta-carotene and retinol concentrations are unrelated with the risk for ALS.
It has been suggested that nitric oxide (NO) could be implicated in the pathogenesis of multiple sclerosis (MS). Recently, two groups reported increased cerebrospinal fluid (CSF) nitrate levels (oxidation product that provides an indirect estimation of NO) in MS patients. However, another group did not confirm these findings. We studied the CSF and plasma levels of nitrate with a kinetic cadmium reduction method in 11 MS patients and 25 matched controls. The CSF nitrate levels and the CSF/plasma nitrate ratio did not differ significantly between the two study groups. Plasma nitrate levels were nearly significantly lower in MS patients. CSF and plasma nitrate levels did not correlate with age at onset and duration of the disease in the patient group. These data suggest that measurement of CSF levels of nitrate is not a marker of the activity of MS.
We report the case of a 3-year-old girl, the only child of a nonconsanguineous couple without relevant antecedents, who was born with hydranencephalic-hydrocephalic syndrome diagnosed by ultrasonography at gestation week 28, and who was treated during the neonatal period by implantation of a ventriculoperitoneal shunt. She showed severe mental retardation, and died at age 4 years following an acute respiratory infection. Due to persistently high lactic acid levels in blood, muscle and skin biopsies were taken. Analysis of muscle biopsies revealed microscopic and ultrastructural alterations typical of mitochondrial disorders, and low levels of complexes III and IV of the mitochondrial respiratory chain. The enzymes of the pyruvate dehydrogenase complex showed normal activities in cultured skin fibroblasts. These findings raise the possibility that at least some cases of congenital hydranencephalic-hydrocephalic syndrome may be due to alterations in the mitochondrial respiratory chain.
OBJECTIVE: To investigate muscle metabolism in elderly people with hip fracture. METHODS: Free carnitine, carnitine esters, and respiratory chain enzyme activity were measured in muscle tissue from 54 patients over 65 years who underwent surgery for hip fracture, and from 40 healthy controls. RESULTS: Eighty-five percent of patients older than 85 have either abnormal carnitine distribution or defects in the respiratory chain. CONCLUSION: Elderly patients with hip fracture have muscle metabolic alterations that may contribute to neuromuscular impairment and be amenable to therapy.
A 60-year-old woman had developed ptosis, progressive external ophthalmoplegia and action tremor over the last ten years. Physical examination also revealed short stature and retinal pigmentation. Anaerobic forearm exercise test showed increase of basal lactate and rise of lactate/piruvate index. Biceps biopsy displayed numerous ragged red fibers. Respiratory chain studies were consistent with complex I deficiency. Point mutations or deletions in mitochondrial DNA were not found. MR identified a diffuse leukoencephalopathy over both cerebral hemispheres, mesencephalon, pons and cerebellum. The late and sporadic onset of a progressive external ophthalmoplegia outlining a Kearns-Sayre syndrome is striking. A leukoencephalopathy associated with mitochondrial encephalomyopathy is an infrequent finding. The action tremor of this patient could be symptomatic of her mitochondrial disfunction.
We studied a 21-year-old patient with clinical, biochemical and histochemical evidence of myophosphorylase deficiency and unusual repetitive episodes of pigmenturia. His muscle biopsy also revealed morphological signs of mitochondrial proliferation and a defect of complex I of the respiratory chain. His mother had exercise intolerance without myoglobinuria and no histochemical evidence of myophosphorylase deficiency. In muscle, the mother showed some ragged-red fibers, normal respiratory chain levels and a significant residual phosphorylase activity. Molecular genetic analysis revealed that the proband was homozygous for the mutation commonly found in McArdle's disease. The mother, father, and the five siblings were all heterozygous for the same mutation. Mitochondrial DNA analysis of the proband's muscle failed to demonstrate known mutations associated with his clinical pattern. Moreover, we sequenced his tRNA(Leu(UUR)) gene, a hot spot for mutations, showing no abnormality.
We compared cerebrospinal fluid (CSF) and serum levels, and the CSF/serum ratio of alpha-tocopherol (vitamin E), measured by HPLC, in 36 patients with multiple sclerosis (MS) and 32 matched controls. The mean CSF vitamin E levels and the CSF/serum vitamin E ratio did not differ significantly between the two study groups. The serum levels of vitamin E and the serum vitamin E/cholesterol ratio were significantly lower in MS patients when compared with controls (P < 0.05 and P < 0.01, respectively). These values were not correlated with age, age at onset and duration of the disease in the patients group. These results suggest that CSF vitamin E concentrations are not a marker of activity of MS activity.
We assessed free carnitine (FC) and acylcarnitine esters (AC) in both cerebrospinal fluid (CSF) and plasma from 24 patients with diagnostic criteria for Alzheimer's disease (AD), and from 28 healthy matched-controls. We found no significant correlation between FC and AC levels in CSF. FC and AC levels in CSF did not differ significantly between AD patients and controls, but plasma FC levels were significantly lower in AD patients. CSF and plasma FC and AC levels did not correlate with age, age at onset of AD, duration of AD, and scores of the Minimental State Examination of Folstein. Although these results suggest that CSF carnitine levels are apparently unrelated with the risk for AD, the trend of the FC/AC ratio to be higher in AD patients might suggest the possibility of a lower carnitine acetyltransferase activity in AD, as previously reported in some brain areas.
Respiratory enzyme activities and steady-state level of two mitochondrial-encoded transcripts were quantified in heart muscle biopsies from patients suffering various types of cardiomyopathies unrelated to mitochondrial primary disorders. We have found that although the mitochondrial DNA copy number and the concentration of COI and ND4 transcripts remain fairly constant, there is an important increase (up to 6-fold) in respiratory enzyme activities affecting to several oxidative phosphorylation complexes. Idiopathic dilated cardiomyopathy shows the greatest increase, followed by ischemic heart and ventricular hypertrophy due to aortic stenosis. The results suggest an energetic compensatory mechanism in the heart muscle, in the absence of mitochondrial proliferation or activation of mitochondrial gene expression.
We measured CSF and plasma levels of cGMP in 22 patients with Parkinson's disease (PD) and in 28 age and sex-matched controls. PD patients had similar plasma cGMP levels than those of controls, although they showed a non-significant trend towards higher CSF cGMP levels (P=0.07). PD patients treated with levodopa showed significantly higher CSF cGMP levels than those not treated with this drug (P<0.01), and controls (P<0.01). However, treatment with dopamine agonists did not influence CSF cGMP levels. Plasma and CSF levels of cGMP did not correlate with age at onset, duration, and severity of PD. These results suggest that changes in the concentration of cGMP in CSF of patients with PD are not related with the disease, but rather with levodopa therapy.
We found a variable defect of complex I of the mitochondrial respiratory chain, ranging in severity from 25% to 63% of control values, in muscle of patients with Huntington's disease (HD). The most severe defect was observed in the patient with the greatest expansion of CAG triplets. Muscle morphology showed myopathic changes such as moth-eaten fibers, angulated fibers, increased subsarcolemmal oxidative activities, or an increased number of enlarged mitochondria with abnormal cristae. Multiple mitochondrial DNA deletions were found by polymerase chain reaction (PCR) analysis in muscle of the patient with the most severe defect of complex I. Our data further support the involvement of energetic defects and oxidative damage in muscle of patients with HD.
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We measured the CSF and plasma levels of glutamate, glutamine, aspartate (only in plasma), asparagine, glutamine, glycine and GABA in 37 patients with Alzheimer's disease and in 32 matched controls. We used an ion-exchange chromatography method. When compared to controls, AD patients had higher CSF glutamate and glycine levels, higher plasma levels of aspartate and glycine, and lower plasma levels of asparagine and GABA. When expressed relative to CSF proteins, CSF levels of glutamate and glycine remained higher, and CSF asparagine levels were lower in AD patients than in controls. The CSF levels of the amino acids measured were not correlated with the clinical features of AD with the exception of plasma GABA levels with duration of the disease. Our results might suggest a possible pathogenetic role of neurotransmitter amino acids in AD.
We measured the CSF levels of 21 and the plasma levels of 24 amino acids in 37 patients with Alzheimer's disease (AD) and in 32 matched controls. We used an ion-exchange chromatography method. When compared with controls, AD patients had lower CSF levels of phosphoserine, citrulline, alfa-aminobutyric acid, methionine, and ethanolamine; and higher CSF levels of threonine, serine, lysine, histidine and arginine. However, when expressed relative to CSF protein, CSF levels of serine, lysine, histidine, and arginine, were normal. AD patients had higher plasma levels of phosphoserine, threonine, citrulline, hydroxyproline, and proline; and lower plasma levels of alfa-aminobutyric acid, methionine, leucine and ethanolamine. The CSF/plasma ratios of phosphoserine, serine, citrulline, alfa-aminobutyric acid and arginine were significantly lower in AD patients than those of controls. CSF amino acid levels were not related with the duration and severity of the disease.