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A Barrientos

Publications and source records attributed to A Barrientos.

At least 73 records · Page 4Linked to original sources
PubMed1996

Absence of relationship between the level of electron transport chain activities and aging in human skeletal muscle.

We investigated the relationship between age and respiratory chain function of skeletal muscle mitochondria in 132 control individuals (15 to 95 years old). Muscle mitochondria were studied polarographically and spectrophotometrically. By regression analysis, we found a significant inverse correlation between age and oxygen uptake linked to substrate oxidation (succinate, glutamate-malate or ascorbate-TMPD). However, this significance disappeared after including physical activity and tobacco consumption as confounding variables in a multivariate statistical analysis. Similarly, the activity of respiratory chain complexes individually measured did not decline with age. It therefore appears that respiratory chain activity in human skeletal muscle mitochondria is substantially undamaged during the aging process.

Adolescent↗
PubMed1996

A nuclear defect in the 4p16 region predisposes to multiple mitochondrial DNA deletions in families with Wolfram syndrome.

Wolfram syndrome is a progressive neurodegenerative disorder transmitted in an autosomal recessive mode. We report two Wolfram syndrome families harboring multiple deletions of mitochondrial DNA. The deletions reached percentages as high as 85-90% in affected tissues such as the central nervous system of one patient, while in other tissues from the same patient and from other members of the family, the percentages of deleted mitochondrial DNA genomes were only 1-10%. Recently, a Wolfram syndrome gene has been linked to markers on 4p16. In both families linkage between the disease locus and 4p16 markers gave a maximum multipoint lod score of 3.79 at theta = 0 (P<0.03) with respect to D4S431. In these families, the syndrome was caused by mutations in this nucleus-encoded gene which deleteriously interacts with the mitochondrial genome. This is the first evidence of the implication of both genomes in a recessive disease.

Adult↗
PubMed1996

Double renal transplant from infant donors. A good alternative for adult recipients.

Several groups have reported technical complications and poor graft survival rates in kidney transplants from pediatric donors to adult recipients. Increased incidences of acute rejections, vascular thrombosis, and early glomerulosclerotic lesions have led many groups to abandon this graft combination. Over the last 4 years, we have set up a program of two-kidney transplantation from cadaveric infant donors under age 3 years, which to date includes 15 adult recipients. Thirteen of these grafts are currently functioning at least as well as those from adult donors, after a mean follow-up of 1.5 years. Our surgical and therapeutic procedures have led to a minimization of the early complications reported by other groups. With this transplantation procedure, the patients receive double the number of nephrons, which will probably give them better long-term function. The encouraging results achieved by our group may help change the current consideration of pediatric donors as "suboptimal" ones.

Adolescent↗
PubMed1996

The effect of zidovudine on skeletal muscle mtDNA in HIV-1 infected patients with mild or no muscle dysfunction.

Zidovudine (ZDV), a nucleoside analogue which inhibits viral replication, is currently used in the treatment of type 1 human immunodeficiency virus (HIV-1) infection. It has been considered to be the cause of an acquired form of myopathy associated with a depletion of mitochondrial DNA (mtDNA) in muscle fibres, although the fact that the patients previously studied were clearly symptomatic, and the theoretical difficulty in differentiating on HIV-related myopathy from the effects of ZDV, led to a controversy on the possible deleterious effect of ZDV on muscle fibres. We studied the muscle biopsy taken from 42 HIV-1 infected patients, regardless of their medical complaints, and two series of controls: 12 HIV-negative patients suffering from diverse neuromuscular diseases and 10 normal patients who underwent orthopaedic surgery. Whole DNA was extracted following standard procedures and analysed by means of Southern blotting and polymerase chain reaction (PCR). We found that mtDNA was only depleted in HIV-1 infected patients treated with ZDV, but not in controls or patients untreated with this antiretroviral drug. Moreover, the depletion was more marked in patients who either presented weakness, myalgia, raised serum creatine kinase (CK), or ragged-red fibres. Mitochondrial DNA deletions were found in low proportion in all groups of patients, regardless of their HIV infection or ZDV status, but not in normal controls. We conclude that ZDV treatment in HIV-1 positive patients produces depletion of muscle mtDNA. The depletion can be demonstrated even in asymptotic patients, but is more marked in patients with clinical symptoms or abnormalities in their muscle biopsies. Other mtDNA abnormalities such as deletions seemed to be more related to other circumstances concurring in HIV-1 infected patients than to the effects of ZDV.

Adult↗
PubMed1996

Long-term erythropoietin in rats with reduced renal mass.

Hematocrit increase with recombinant erythropoietin (rEPO) has been associated with increased progression of renal insufficiency in experimental models of renal mass reduction. The aim of the present study was to assess the effects of therapy with rEPO and various antihypertensives on the progression of chronic renal insufficiency and on arterial hypertension in an experimental model of renal mass reduction. Rats subjected to a two-thirds nephrectomy were randomly assigned to an untreated control group or to therapy with rEPO (subcutaneously, at an initial dose of 40 U/kg thrice weekly), rEPO plus verapamil (subcutaneously, 0.5 mg/kg/day), or rEPO plus enalapril (orally, 50 mg/l in the drinking water). Combining enalapril and rEPO therapy controlled systemic blood pressure (BP) and the increase in proteinuria. Glomerular injury, as assessed 16 weeks after renal ablation, was more marked in the animals treated with rEPO with or without either antihypertensive. The morphometric analyses showed greater glomerular tuft areas in the three groups receiving rEPO than in the controls. The glomerular tuft area was directly correlated with the rate of glomerulosclerosis. In about 11% of the rEPO-treated hypertensive rats, the lesions showed severe hypertensive vasculopathy; in the animals treated with rEPO plus enalapril, the lesions were less severe. We conclude that therapy with rEPO was associated to renal damage which could not be attenuated by enalapril despite controlling BP and proteinuria, and may have a nonhemodynamic cause. Therapy with rEPO might trigger lesions usually associated with severe arterial hypertension; concomitant therapy with enalapril attenuates hypertensive vasculopathy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Abnormalities of heme biosynthesis in experimental acute renal failure.

Several abnormalities of porphyrin metabolism have been described in patients with end-stage renal failure. Because the heme biosynthetic pathway in acute renal failure has not been studied hitherto, an experimental model was therefore induced in 30 dogs by ligation and transection of both ureters. Forty-eight h after this procedure, anemia and uremia developed, erythrocyte aminolevulinate dehydratase activity decreased, and plasma porphyrins increased in these 30 dogs, whereas seven sham-operated animals did not exhibit any alteration of these parameters. Uremic plasma showed a capacity to inhibit aminolevulinate dehydratase activity (mean, 11.1 +/- 5.8%) when incubated in vitro with erythrocytes from healthy dogs. Such findings are similar to those reported in uremic patients on hemodialysis or on continuous ambulatory peritoneal dialysis. Twenty-three of the 30 animals underwent a hemodialysis session (180 min) 48 h after ureteral ligation, using a polyacrylonitrile membrane dialyzer. In addition to reducing serum creatinine and urea levels, this procedure significantly reduced plasma porphyrin values. However, the activity of erythrocyte aminolevulinate dehydratase and the plasma capacity to inhibit this enzyme were not modified after the hemodialysis session. This results described here show that some of the abnormalities of heme biosynthesis described in chronic renal failure are detected early in an experimental model of acute renal failure. This study also confirms that, although most plasma porphyrins circulate bound to proteins, hemodialysis may reduce levels of plasma porphyrins when a high permeability membrane is used.

Acute Kidney Injury↗
PubMed1996

Effects of recombinant human erythropoietin on porphyrin metabolism in uremic patients on hemodialysis.

Recombinant human erythropoietin (r-HuEPO) is being successfully used for the treatment of uremic anemia. Several abnormalities of heme biosynthetic pathway have been described in patients with end-stage renal failure. In this condition, the activity of erythrocyte porphobilinogen deaminase has been found to be slightly increased. If this enzyme were to be the key enzyme in erythroid heme regulation, its activity would be increased to an even greater degree during the correction of uremic anemia. To assess this hypothesis, this study followed the variations of this and other parameters of porphyrin metabolism over 12 months of erythropoietin therapy in eight patients with nephrogenic anemia who underwent hemodialysis. By the first month of therapy, an increase of the previously depressed erythrocyte activity of aminolevulinate dehydratase was already evident, in coincidence with a nonsignificant increase of the reticulocyte count. The activity of this enzyme reached its maximal level by Month 3, and did not change up to Month 10. The porphobilinogen deaminase hyperactivity normalized at Month 4. By Month 12, in coincidence with the reduction of erythropoietin doses, the maximal levels of erythrocyte protoporphyrin, and the decrease in aminolevulinate dehydratase activity, the porphobilinogen deaminase values started to increase once again. In conclusion, the administration of r-HuEPO to hemodialyzed patients induced transient normalization of the previously observed porphyrin metabolism abnormalities. However, erythrocyte porphobilinogen deaminase activity did not rise concomitantly with the increase in hematocrit or hemoglobin values, but it did diminish during treatment. Therefore, porphobilinogen deaminase did not behave as a controlling enzyme in heme synthesis during the r-HuEPO-induced correction of uremic anemia.

Adult↗
PubMed1996

Autosomal recessive Wolfram syndrome associated with an 8.5-kb mtDNA single deletion.

Wolfram syndrome (MIM 222300) is characterized by optic atrophy, diabetes mellitus, diabetes insipidus, neurosensory hearing loss, urinary tract abnormalities, and neurological dysfunction. The association of clinical manifestations in tissues and organs unrelated functionally or embryologically suggested the possibility of a mitochondrial implication in the disease, which has been demonstrated in two sporadic cases. Nonetheless, familial studies suggested an autosomal recessive mode of transmission, and recent data demonstrated linkage with markers on the short arm of human chromosome 4. The patient reported here, as well as her parents and unaffected sister, carried a heteroplasmic 8.5-kb deletion in mtDNA. The deletion accounted for 23% of mitochondrial genomes in lymphocytes from the patient and approximately 5% in the tissues studied from members of her family. The presence of the deletion in the patient in a proportion higher than in her unaffected parents suggests a putative defect in a nuclear gene that acts at the mitochondrial level.

Base Sequence↗
PubMed1996

Occult lead intoxication as a cause of hypertension and renal failure.

BACKGROUND: The true incidence of lead (Pb) overload as a cause of chronic renal failure (CRF) is unknown. Also, it is unclear if CRF per se could generate an increment in the body Pb burden. Most studies of chronic Pb intoxication have been performed on cohorts or patients with a past history of occupational exposure. Therefore we studied the body Pb burden in CRF of known aetiology versus those patients with CRF with gout and hypertension of unclear aetiology without a past history of Pb exposure. In addition we studied patients diagnosed with essential hypertension. METHODS: We studied 296 patients lacking a past history of Pb exposure, who were subdivided into four groups: group I (n = 30), normal control subjects; group II (n = 104), patients with 'essential' hypertension and normal renal function; group III (n = 132), patients with CRF of uncertain aetiology in association with hypertension and/or gout, and group IV (n = 30), patients with CRF of known aetiology. The blood and urine Pb levels were assessed before and after an EDTA test. RESULTS: No abnormal test results were obtained for patients in groups I and IV. The EDTA test was abnormal in 16 patients (15.4%) in group II and in 74 patients (56.1%) in group III. A positive correlation was observed between plasma creatinine levels and post-EDTA urinary Pb in group III, but not in group I. No correlation regarding plasma creatinine and the duration of hypertension or gout were demonstrated. The bone Pb levels, measured in 12 patients with pathological EDTA test results, were positively correlated to the plasma creatinine levels. CONCLUSIONS: A high percentage of patients with gout, hypertension, and CRF have an excessive Pb burden, and about 15% of the patients diagnosed as 'essential' hypertensives also show high Pb burdens. It is remarkable that a history of overt Pb exposure was lacking in the whole study population.

Body Burden↗
PubMed1995

[Progressive external ophthalmoplegia and the Kearns-Sayre syndrome: a clinical and molecular study of 6 cases].

The Kearns-Sayre syndrome (KSS) associates progressive external ophthalmoplegia initiating prior to the age of 20 years and pigmentary retinitis with a series of other heterogeneous clinical manifestations. The incomplete syndrome is usually denominated progressive external ophthalmoplegia (PEO)-plus which is a sporadically appearing mitochondrial cytopathy associated with large deletions of a variable proportion of mitochondrial DNA (mtDNA) molecules. Six patients with PEO-plus/KSS in whom muscle biopsy was performed following a complete clinical study are described. The muscle was processed by conventional histochemical techniques, electron microscopy, and genetic study (Southern transference, polymerase chain reaction, restriction cartography and both manual and automatic sequencing). The percentage of mutated mtDNA molecules for each patient was obtained by densitometry. The 6 patients presented multiorganic clinical manifestations characteristics of most mitochondrial diseases. The presence of destructured red fibers were observed in all the biopsies. All the patients presented a deletion in the mtDNA of a size between 4,861 to 7,437 base pairs (bp). All the deletions appeared flanked by direct repetitions from 4 to 13 bp and one also presented inverse repetitions from 5 to 6 bp in the zone next to the rupture point. In the 6 cases heteroplasmia was observed with a variable percentage of deleted molecules from 23 to 56%. The molecular basis of progressive external ophthalmoplegia-plus/Kearns-Sayre syndrome appears to be the existence of sole, large deletions in the mitochondrial DNA with the varying in location and percentage conditioning the appearance of different phenotypes similar among themselves. The 7,437 base pair deletion was the most frequently observed in the patients analyzed.

Adolescent↗
PubMed1995

The 9-bp deletion in region V of mitochondrial DNA: evidence of mutation recurrence.

A deletion of one of the two copies of a 9-bp direct repeat sequence (CCCCCTCTA) in region V of mitochondrial DNA has previously been used as a polymorphic anthropological marker for people of east Asian origin, and to a lesser extent, in Oceanian and African populations. We report the presence of the 9-bp deletion in homoplasmy in skeletal muscle fibers and lymphocytes of a Spanish Caucasian individual. Other mitochondrial DNA polymorphisms associated with the 9-bp deletion characteristic of other populations were not present. Our results suggest that the 9-bp deletion probably originated independently in the maternal lineage of the propositus, and that it can thus be described as a recurrent mutation.

Anthropology↗
PubMed1995

Alterations in renal endothelin production in rats with reduced renal mass.

Renal endothelin-1 (ET-1) production is diminished in spontaneously hypertensive rats. An increase has been reported of renal ET-1 production associated with progression of renal disease in rats with reduced renal mass. The purpose of the present study was to investigate the evolution over time of the urinary ET-1 excretion in an experimental model of renal mass reduction not caused by renal infarction. Rats were subjected to 2/3 nephrectomy (right nephrectomy and resection of the lower left renal pole) and thereafter randomly assigned to a no-treatment control group or to treatment with recombinant erythropoietin, recombinant erythropoietin plus verapamil, or recombinant erythropoietin plus enalapril. The urinary ET-1 excretion was decreased by week 16 after nephrectomy as compared with healthy animals and with the levels 6 weeks after nephrectomy. The temporal evolution of urinary ET-1 excretion in the various groups of rats showed a trend toward decrease in all groups except the one receiving enalapril. The urinary ET-1 excretion correlated directly with creatinine clearance and inversely with tubulointerstitial damage. We observed an inverse correlation between urinary ET-1 excretion and arterial blood pressure 16 weeks after nephrectomy. These results indicate that renal ET-1 production decreases with the progression of renal disease and in relation with the severity of tubulointerstitial damage. The decrease in renal ET-1 production might contribute to the development and perpetuation of renal disease-associated arterial hypertension; this situation may be favorably modified by the use of enalapril.

Animals↗
PubMed1995

Efficiency of three different hemodialysis membranes for plasma porphyrin removal.

To assess the capability of three different membranes to remove porphyrins, plasma and dialysate porphyrin levels were fluorometrically measured in 10 patients with end-stage renal failure who were on hemodialysis. Three different hemodialysis membranes were used: cuprophan, polyacrylonitrile, and cellulose triacetate. Total plasma porphyrin concentrations decreased after dialysis, but to a lesser extent when using the cuprophan membrane (19%) than with the polyacrylonitrile (26%) or cellulose triacetate (30%) membranes (P < 0.01). However, since the free plasma porphyrin fraction remained unchanged, it can be assumed that the equilibrium between protein-bound and non-protein-bound (free) porphyrins is displaced toward the latter fraction. Dialysate porphyrin levels were lower (P < 0.01) when using the cuprophan membrane (10.1 micrograms/session) than when using polyacrylonitrile (17.8 micrograms/session) and cellulose triacetate (21.9 micrograms/session). Although most of the plasma porphyrins are protein bound, our results show that hemodialysis can remove significant amounts of non-protein-bound (free) porphyrins. The polyacrylonitrile and cellulose triacetate membranes had a greater capacity for porphyrin removal than cuprophan. Thus, two high-permeability membranes (polyacrylonitrile and cellulose triacetate) should be used whenever a reduction of plasma porphyrin levels is desired.

Acrylic Resins↗