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Biomedical subjects

R Pons

Publications and source records attributed to R Pons.

At least 19 recordsLinked to original sources
PubMed2000

Effects of inhaled glaucine on pulmonary responses to antigen in sensitized guinea pigs.

The alkaloid (S)-(+)-1,2,9,10-tetramethoxyaporphine (glaucine) is a phosphodiesterase 4 inhibitor with bronchodilator and anti-inflammatory activity in vitro. In this study, we examined the in vivo effects of glaucine on an animal model of asthma. In ovalbumin sensitized guinea pigs, inhaled glaucine (10 mg ml(-1), 3 min) inhibited the acute bronchoconstriction produced by aerosol antigen (antigen response was 256+/-42 and 95+/-14 cm H(2)O l(-1) s(-1) in control and glaucine-treated animals, respectively; P<0.05). Pretreatment with glaucine (10 mg ml(-1), 10 min inhalation, 30 min pre- and 3 h post-antigen exposure) markedly reduced airway hyperreactivity to histamine, eosinophil lung accumulation, and increased eosinophil peroxidase activity in bronchoalveolar lavage fluid 24 h after exposure of conscious guinea pigs to aerosol antigen. In addition, inhaled glaucine (5-10 mg ml(-1), 3 min) inhibited the microvascular leakage produced after inhaled antigen at all airway levels. These data support the potential interest of phosphodiesterase 4 inhibitors in asthma treatment.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2000

Clinical and molecular heterogeneity in very-long-chain acyl-coenzyme A dehydrogenase deficiency.

Very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency is an increasingly recognized defect of mitochondrial fatty acid beta-oxidation manifesting with episodes of metabolic decompensation or isolated recurrent myoglobinuria. In this report the clinical, biochemical, and molecular studies in a series of five patients (four Italian and one Spanish) with this disorder are discussed. Biochemical studies included the determination of fibroblast substrate oxidation rates and enzyme activity and Western blot analysis of VLCAD protein. Molecular analysis was performed by sequencing the VLCAD gene from the genomic DNA. Clinical features were within the spectrum previously reported. Four patients presented in infancy or childhood with episodes of severe metabolic decompensation and dicarboxylic aciduria. Two exhibited cardiomyopathy. The fifth patient presented with isolated recurrent rhabdomyolysis, with no cardiomyopathy or dicarboxylic aciduria. In all patients a significant loss of VLCAD activity associated with a marked reduction of VLCAD protein levels occurred. Molecular analysis disclosed one novel missense mutation (Cys437Tyr) and four previously reported mutations, including two missense substitutions (Phe418Leu and Arg419Trp), a single amino acid deletion (Lys258del), and one splice site mutation (IVS8-C(-2)), which was present in all four Italian patients. All patients exhibited compound heterozygosity. The phenotypic variability and the high genotypic heterogeneity of this hereditary metabolic disorder is reported.

Acyl-CoA Dehydrogenase↗
PubMed1999

Bronchodilator and anti-inflammatory activities of glaucine: In vitro studies in human airway smooth muscle and polymorphonuclear leukocytes.

1. Selective phosphodiesterase 4 (PDE4) inhibitors are of potential interest in the treatment of asthma. We examined the effects of the alkaloid S-(+)-glaucine, a PDE4 inhibitor, on human isolated bronchus and granulocyte function. 2. Glaucine selectively inhibited PDE4 from human bronchus and polymorphonuclear leukocytes (PMN) in a non-competitive manner (Ki=3.4 microM). Glaucine displaced [3H]-rolipram from its high-affinity binding sites in rat brain cortex membranes (IC50 approximately 100 microM). 3. Glaucine inhibited the spontaneous and histamine-induced tone in human isolated bronchus (pD2 approximately 4.5). Glaucine (10 microM) did not potentiate the isoprenaline-induced relaxation but augmented cyclic AMP accumulation by isoprenaline. The glaucine-induced relaxation was resistant to H-89, a protein kinase A inhibitor. Glaucine depressed the contractile responses to Ca2+ (pD'2 approximately 3.62) and reduced the sustained rise of [Ca2+]i produced by histamine in cultured human airway smooth muscle cells (-log IC50 approximately 4.3). 4. Glaucine augmented cyclic AMP levels in human polymorphonuclear leukocytes challenged with N-formyl-Met-Leu-Phe (FMLP) or isoprenaline, and inhibited FMLP-induced superoxide generation, elastase release, leukotriene B4 production, [Ca2+]i signal and platelet aggregation as well as opsonized zymosan-, phorbol myristate acetate-, and A23187-induced superoxide release. The inhibitory effect of glaucine on superoxide generation by FMLP was reduced by H-89. 5. In conclusion, Ca2+ channel antagonism by glaucine appears mainly responsible for the relaxant effect of glaucine in human isolated bronchus while PDE4 inhibition contributes to the inhibitory effects of glaucine in human granulocytes. The very low PDE4/binding site ratio found for glaucine makes this compound attractive for further structure-activity studies.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Is visual anticipation of collision during self-motion related to perceptual style?

We have previously shown that during self-motion in car driving situations, the perception of another car's trajectory relies both on global visual information such as the optical flow field, and on local visual information such as the optical motion of the other car and the relative optical motion of the other car with respect to fixed elements in the environment. Here, we studied the environmental factors that contribute to perceptual judgements in relation to the observer's perceptual style (visual-field dependence vs. visual-field independence). In an experiment, observers were presented with visual scenes corresponding to the curvilinear self-motion of a driver approaching an intersection where another vehicle was arriving perpendicularly. The factors manipulated were the presence or absence of a spatial reference point (road sign near the intersection), environmental complexity ("road" or "spot" scenes), and the degree of field dependence/independence. Nine field-independent (FI) subjects and seven field-dependent (FD) subjects were asked to predict whether the other vehicle would reach the intersection before or after they would. Their responses were analyzed. Overall, subjects' judgements were more accurate with road environments and with a road sign, suggesting that the relative motion of the other vehicle with respect to fixed elements in the environment provides additional useful information. FI subjects were significantly more accurate than FD subjects, suggesting that the former are better at picking up relevant dynamic information in a complex environment.

Adult↗
PubMed1998

Very-long-chain acyl-coenzyme A dehydrogenase deficiency in a child with recurrent myoglobinuria.

A 9-year-old boy had recurrent episodes of myoglobinuria and normal urinary organic acid profile. Very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency was detected biochemically in cultured skin fibroblasts and confirmed by Western blot analysis. The patient had a distinctive plasma fatty-acid profile, which was present even between attacks. Early diagnosis of this disorder is important because of the apparently protective effect of an appropriate dietary regimen.

Acyl-CoA Dehydrogenase, Long-Chain↗
PubMed1997

Bronchodilator and anti-inflammatory activities of SCA40: studies in human isolated bronchus, human eosinophils, and in the guinea-pig in vivo.

There is currently interest in the use of inhibitors of cyclic nucleotide phosphodiesterases (PDE) as potential anti-asthma agents. In this study we examined the effects of SCA40 (6-bromo-8-methylaminoimidazol-[1,2-a] pyrazine-2-carbonitrile), a preferential inhibitor of PDE 3 also endowed with PDE 4 and 5 inhibitory activities, on isolated bronchus and eosinophil functions and in an animal model of asthma. SCA40 (1 nM-0.1 mM) produced concentration-dependent inhibition of spontaneous and stimulated tone of human isolated bronchus and reached a maximal relaxation similar to that of theophylline (3 mM). The potency (-log EC50 values) of SCA40 against spontaneous tone (6.52 +/- 0.10) was greater than against tone raised by equieffective concentrations (approximately 70%) of histamine (5.76 +/- 0.06), leukotriene C4 (5.44 +/- 0.11), and acetylcholine (4.98 +/- 0.09). In the presence of cytochalasin B, the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP; 0.5 microM) induced leukotriene C4 production in human eosinophils isolated in discontinuous metrizamide gradients. The production of leukotriene C4 was inhibited by SCA40 in a concentration-related fashion (-log IC50 = 6.04 +/- 0.20; n = 6). Rolipram, a selective PDE 4 inhibitor, was also effective (-log IC50 = 7.29 +/- 0.32) but the selective PDE 3 inhibitor SKF94120 was scarcely effective (< 10% inhibition for 10 microM). In ovalbumin sensitized guinea-pigs, SCA40 (1 mg kg(-1), i.p.) given 30 min before antigen challenge significantly inhibited the acute bronchoconstriction produced by aerosol antigen (5 mg ml(-1), 30 s) (antigen response was 185 +/- 13 and 91 +/- 21 cmH2O l(-1) s(-1) in control and SCA40-treated animals, respectively, P < 0.05). Pretreatment with SCA40 (1 mg kg(-1), i.p., 30 min pre- and 3 h post-antigen exposure) prevented airway hyperreactivity to histamine which developed 24 h after exposure of conscious guinea-pigs to aerosol antigen. Eosinophil lung accumulation that accompanied airway hyperreactivity was also inhibited by SCA40 (from 6.15 +/- 0.86 in control to 1.27 +/- 0.27 in treated animals; expressed as eosinophils x 10(6); P < 0.05). SCA40 (1 mg kg(-1), i.p.) also inhibited the microvascular leakage produced after inhaled antigen (5 mg ml(-1), 30 s) at all airway levels. The haemodynamic effects of SCA40 (1 mg kg(-1), i.p.) consisted of a rapid decrease (peak at 5 min) in mean arterial blood pressure (-39.4 +/- 2.4%) and tracheal mucosal blood flow (-13.5 +/- 2.0%) that slowly recovered with time. These data support previous work showing that PDE inhibition results in antispasmogenic and anti-inflammatory effects. SCA40 was effective in vitro and in vivo and these effects are probably related to its activity as a mixed PDE inhibitor.

Animals↗
PubMed1997

Deficient muscle carnitine transport in primary carnitine deficiency.

Primary carnitine deficiency is associated with deficient blood and tissue carnitine concentrations. The clinical syndrome is dominated by heart and skeletal muscle symptoms, and the clinical response to oral carnitine supplementation is life-saving. Carnitine uptake has been shown to be defective in cultured skin fibroblasts and leukocytes obtained from patients with this condition. We report a new case of primary carnitine deficiency and offer direct evidence consistent with an impairment of carnitine uptake in differentiating muscle culture. The patient presented with severe and progressive cardiomyopathy and moderate proximal limb weakness. Plasma and muscle carnitine levels were very low, and the maximal rate of carnitine transport in cultured fibroblasts was deficient. An asymptomatic sister with intermediate levels of carnitine in plasma showed partially deficient carnitine uptake in fibroblasts, indicating heterozygosity. The patient's condition improved dramatically with oral carnitine therapy. Further studies were performed in cultured muscle cells at different stages of maturation, which demonstrated deficient maximal rates of carnitine uptake. Our findings are consistent with the concept that primary carnitine deficiency is the result of a generalized defect involving carnitine transport across tissue membranes.

Biological Transport↗
PubMed1996

The clinical spectrum of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency.

Four patients with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency are presented. Clinical onset in the form of acute encephalopathy occurred between the ages of 9 months and 3 years. The clinical course included recurrent metabolic crises in 4 patients, cardiac involvement and retinopathy in 3, and myopathy in 2. None had signs of peripheral neuropathy. Three patients died and one is currently well. Hypoketotic hypoglycemia with C6-C14 3-hydroxy-dicarboxylic aciduria during metabolic crises associated with decreased plasma carnitine levels was the main biochemical finding. Enzymologic studies disclosed long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency in all patients. Homozygosity for a G to C mutation at position 1528 in the encoding region of the enzyme was found in 2 patients. Histologic and electron microscopic studies of liver biopsy specimens revealed steatosis in 3 patients and mitochondrial abnormalities in 2. Skeletal muscle biopsies disclosed nonspecific degenerative changes in 2 patients and were normal in the remaining 2. Ultrastructural abnormalities in mitochondria were found in 3 patients. A review of the literature combined with the data from our series (total 22 patients) disclosed acute clinical onset in 77% of cases and subacute in 23%. In the combined series, the average age at onset was 11 months, family history was positive in 32% of patients and overall mortality was 50%. We describe the clinical spectrum of this disease and emphasize that, among patients with suspected beta-oxidation defects the finding of pigmentary retinopathy should lead to the suspicion of long-chain 3-hydroxyacyl-coenzyme A-dehydrogenase deficiency.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1996

Mitochondrial myopathy simulating spinal muscular atrophy.

A patient with a severe progressive neuromuscular disorder resembling spinal muscular atrophy is reported. The initial muscle biopsy was consistent with a denervating process. DNA analysis did not reveal deletions in exons 7 and 8 of the survival motor neuron gene. Histology, histochemistry, and biochemistry of a second muscle biopsy suggested mitochondrial myopathy accompanying the denervating features. Immunohistochemistry using anti-DNA antibodies revealed only nuclear staining in skeletal muscle, suggesting mitochondrial DNA depletion. In patients with clinical features of spinal muscular atrophy and no deletions in the survival motor neuron gene, mitochondrial DNA depletion should be considered.

Biopsy↗
PubMed1996

Leigh-type neuropathology in Pearson syndrome associated with impaired ATP production and a novel mtDNA deletion.

Pearson syndrome is a systemic disorder of oxidative phosphorylation in infants, predominantly affecting the bone marrow and exocrine pancreas and associated with single deletions in mitochondrial DNA (mtDNA). CNS involvement may occur in patients who survive the infantile hematopoietic disorder. We describe a Pearson syndrome patient who developed neurologic manifestations associated with the pathologic features of Leigh syndrome. Biochemical studies in muscle and skin fibroblasts showed partial deficiencies of complexes I and IV of the respiratory chain. Adenosine triphosphate production in mitochondria isolated from skin fibroblasts was reduced to 25% of controls. We detected a novel 3.6 Kb mtDNA deletion in skin fibroblasts from the proband but not in his mother's white blood cells. Leigh syndrome seems to be the common neuropathologic expression of any disorder causing severe impairment of oxidative energy production in the CNS.

Adenosine Triphosphate↗
PubMed1995

Primary and secondary carnitine deficiency syndromes.

The objective of this article is to review primary and secondary causes of carnitine deficiency, emphasizing recent advances in our knowledge of fatty acid oxidation. It is now understood that the cellular metabolism of fatty acids requires the cytosolic carnitine cycle and the mitochondrial beta-oxidation cycle. Carnitine is central to the translocation of the long chain acyl-CoAs across the inner mitochondrial membrane. The mitochondrial beta-oxidation cycle is composed of a newly described membrane-bound system and the classic matrix compartment system. Very long chain acyl-CoA dehydrogenase and the trifunctional enzyme complex are embedded in the inner mitochondrial membrane, and metabolize the long chain acyl-CoAs. The chain shortened acyl-CoAs are further degraded by the well-known system in the mitochondrial matrix. Numerous metabolic errors have been described in the two cycles of fatty acid oxidation; all are transmitted as autosomal recessive traits. Primary or secondary carnitine deficiency is present in all these clinical conditions except carnitine palmitoyltransferase type I and the classic adult form of carnitine palmitoyltransferase type II deficiency. The sole example of primary carnitine deficiency is the genetic defect involving the active transport across the plasmalemmal membrane. This condition responds dramatically to oral carnitine therapy. The secondary carnitine deficiencies respond less obviously to carnitine replacement. These conditions are managed by high carbohydrate, low fat frequent feedings, and vitamin/cofactor supplementation (eg, carnitine, glycine, and riboflavin). Medium chain triglycerides may be useful in the dietary management of patients with inborn errors of the cytosolic carnitine cycle or the mitochondrial membrane-bound long chain specific beta-oxidation system.

Animals↗
PubMed1991

[Malignant Mediterranean boutonneuse fever. Septic shock of unknown origin?].

Mediterranean Botonous Fever (MBF) is an infectious disease which provokes multisystemic vasculitis due to endothelial proliferation of rickettsia conorii. Its incidence, in our environment, has greatly increased during the last years being endemic in many large cities and their surrounding suburbs. In some cases its evolution is specially malignant resulting in septic shock, adult respiratory distress syndrome, and multiorgan failure. The purpose of this communication is to present a new case of malignant MBF with a bad evolution factor which has not been previously referred to, which is the persistence of vector ticks in the inoculation spot.

Boutonneuse Fever↗
PubMed1988

Tumor recurrence in prostatic urethra following simultaneous resection of bladder tumor and prostate.

A comparative retrospective study was performed on 100 patients who had undergone transurethral resection of a superficial bladder tumor (Ta-Tl) with no associated carcinoma in situ (group 1) and 100 patients who had undergone simultaneous transurethral resection of a superficial bladder tumor (Ta-Tl), with no associated carcinoma in situ, and benign prostatic hyperplasia (group II). Evaluation of the recurrences of prostatic urethral tumors in both groups showed that they appeared in 10 patients (12 recurrences) in group I and 10 patients (14 recurrences) in group II (p = not significant). These data enabled us to rule out the influence of simultaneous transurethral resection in cases of recurrences of prostatic urethral tumors.

Adult↗
PubMed1977

[Anesthesia for esophageal surgery].

At the present time, it is rarely necessary to operate after a digestive perforation complicating the ingestion of a caustic fluid. By contrast, cancer surgery progresses. Anaesthesia requires protection with a high degree of analgesia and curarisation. The use of a Carlens tube during oesophagectomy via a thoracic approach facilitates the surgeon's task. Compensation for blood and water losses should be generous. Insertion of a gastric tube through the plasty makes it possible to avoid gastrostomy. Finally, postoperative artificial ventilation is necessary in these individuals who often suffer from some form of respiratory pathology.

Anesthesia, General↗
PubMed1976

[Cardiovascular disorders in young military personnel. Treatment and readjustment].

The vascular disturbances most commonly encountered in conscripts are examined and the features leading to their diagnosis and the consequent differentiation of organic heart diseases are described. Rhythm variations, auscultation abnormalities (systolic, diastolic and vascular murmurs, additional tones) and ECG alterations thus detected are seen as instances of functional disorders, of a non-dangerous nature that will regress or disappear in the course of time.

Adult↗