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Biomedical subjects

M Vila

Publications and source records attributed to M Vila.

At least 19 recordsLinked to original sources

Phytotoxicity to and uptake of RDX by rice.

Phytoremediation is an emerging strategy to remediate soils contaminated with pollutants like explosives in which plants will uptake, degrade and/or accumulate pollutants. To implement this technology on a site contaminated with RDX, we chose rice, which is able to grow in lagoons, and we tested its ability to grow in soils with high levels of RDX and to decrease RDX concentrations in soil. Rice was grown for 40 days in soil contaminated with increasing [14C]RDX concentrations. Emergence and growth were not affected by RDX. Total chlorophyll content decreased with RDX concentrations of over 500 mg kg(-1). Amounts of chlorophyll were correlated with the appearance of necrosis in leaf extremities. After 40 days, rice translocated 89% of uptaken radioactivity to leaves with 90% in leaf extremities. Analyzes of leaf extracts showed that 95% of radioactivity was RDX in its parent form. Necrosis appears to be a phytotoxic symptom of RDX accumulation.

Biodegradation, Environmental↗

Antioxidant status in patients with sleep apnoea and impact of continuous positive airway pressure treatment.

The episodes of hypoxia/re-oxygenation associated with the respiratory disturbances observed in patients with obstructive sleep apnoea syndrome (OSAS) may induce the generation of oxygen free radicals. Indeed, several studies suggest that OSAS is associated with oxidative stress. The present study tested the hypothesis that patients with OSAS have an alteration in antioxidant defences. The plasma levels of total antioxidant status (TAS), glutathione peroxidase (GPX), gamma-glutamyltransferase (GGT), vitamins A, E, B12 and folate, and homocysteine were determined in 47 patients with OSAS and 37 healthy subjects. Of these, 27 patients who used continuous positive airway pressure (CPAP) for >4 h.night-1 were re-examined 12 months later. Patients with OSAS had lower TAS (1.4+/-0.16 versus 1.50+/-0.10 mmol.L-1), vitamin A (64+/-19 versus 74+/-17 microg.dL-1) and vitamin E levels (1,525+/-499 versus 1,774+/-503 microg.dL-1), and increased values of GGT (42+/-22 versus 32+/-16 U.L-1) than controls. There was no difference between groups in GPX, homocysteine, vitamin B12 and folate plasma levels. CPAP treatment normalised the levels of TAS (1.50+/-0.13 mmol.L-1) and the activity of GGT (30+/-14 U.L-1) without any influence on vitamins levels. In conclusion, the results indicate that patients with obstructive sleep apnoea syndrome have a decreased antioxidant capacity that is partially reversed by continuous positive airway pressure treatment.

Adult↗

EUS-guided mucosectomy for gastrointestinal cancer.

INTRODUCTION: the only way of improving prognosis and survival in gastrointestinal cancer is early diagnosis, with intramucosal localization as confirmed by endoscopic ultrasonography (EUS) or 20-MHz miniprobes (MPs) (T1) being most appropriate. Endoscopic mucosal resection (EMR) has proven effective in the treatment of this sort of lesions. PATIENTS AND METHOD: in a group (18 cases) with 15 cases of superficial gastrointestinal cancer and 3 cases of severe gastric dysplasia, 9 cases (3 esophageal, 4 gastric, 2 rectal) underwent a classic EMR following EUS or a 7.5- and 20-MHz miniprobe exploration. RESULTS: ultrasonographic studies showed a T1 in all but one esophageal case (Tis), and in both gastric dysplasias, with no changed layer structure being demonstrated in the latter (T0). No complications arose with classic EMR, and all 9 patients are alive and free from local or metastatic recurrence, except for one esophageal case, which recurred distally to the esophageal lesion (metachronous). CONCLUSIONS: echoendoscopically-assisted EMR is a safe, effective technique in the endoscopic management of superficial gastrointestinal (esophageal, gastric, colorectal) cancer. Recurrence most likely depends upon cancer multiplicity.

Aged↗

Metabolism of [14C]-2,4,6-trinitrotoluene in tobacco cell suspension cultures.

The metabolism of 2,4,6-trinitrotoluene (TNT) was investigated in tobacco cell suspension cultures amended with [14C]-TNT. Five metabolites were purified and characterized. Temporal evolution of metabolites was monitored during a 120 h incubation period. Metabolites structure was identified by acid and enzymatic hydrolysis, followed by electrospray ionization mass spectrometry and 1H and 13C NMR spectroscopy analyses. The majority of metabolites were conjugates formed by glycose conjugation on the hydroxylamine group of either 2-hydroxylamino-4,6-dinitrotoluene (2-HADNT) or 4-hydroxylamino-2,6-dinitrotoluene (4-HADNT), which led to monoglycoside then to diglycoside. Various diglycosides were observed with gentiobioside or sophoroside formation. Bound residues represented a small fraction (<10% of initial 14C) irrespective of the interval after TNT amendment. Free ADNT was detected only in the medium. This study highlights the central role played by HADNT in the TNT metabolic pathway in tobacco cell suspension culture, and the key role of these compounds and of glycosyltransferases in TNT phytoremediation processes.

Biodegradation, Environmental↗

Contact phase modulation method for acoustic nonlinear parameter measurement in solid.

In this work, a new method to measure in contact the nonlinearity parameter beta of solid plates is presented. A high frequency (HF) tone-burst signal of 20 MHz is inserted in the material by a contact-transducer (with a suitable coupling). A low frequency (LF) pulse (2.5 MHz) is applied to the other face, in the opposite direction, so that the nonlinear interaction of the two waves takes place during the back propagation toward the HF transducer. This collinear interaction creates a phase modulation of the HF tone-burst which is proportional to the beta coefficient and the particle velocity of the LF wave. To determine this particle velocity, in time domain, an extended self-reciprocity calibration of the contact LF transducer is used. A numeric phase demodulation is then performed, giving the beta coefficient of the sample. The proposed method is validated by nonlinearity parameter measurements in Fused Silica. The nonlinear parameter of Fused Silica measured is found to be in good agreement with the literature, and specially the negative sign of this parameter.

Journal Article↗

Testing biennialism in the butterfly Erebia palarica (Nymphalidae: Satyrinae) by mtDNA sequencing.

Abstract The montane butterfly Erebia palarica has an unconfirmed life-cycle length. The genus Erebia shows variability in length of diapause depending on latitude and altitude, which may lead to allochronic differentiation. To test for biennialism and possible asynchronous differentiation, we sequenced the most variable fragments of the mitochondrial control region and the cytochrome oxidase I in forty individuals from the same population, from two consecutive years. No differentiation between cohorts could be detected and therefore the idea of a current annual cycle is supported. We conclude that a biennial cycle may never have been important in this population and we further discuss adaptive strategies this species may have used to confront colder climates.

Adaptation, Physiological↗

COX-2 and neurodegeneration in Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Recent observations link cyclooxygenase type-2 (COX-2) to the progression of the disease. Consistent with this notion, studies with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) show that inhibition and ablation of COX-2 markedly reduce the deleterious effects of this toxin on the nigrostriatal pathway. The similarity between this experimental model and PD strongly supports the possibility that COX-2 expression is also pathogenic in PD.

Animals↗

Plasminogen activator inhibitor-I (PAI-I) polymorphisms in patients with obstructive sleep apnoea.

Cardiovascular diseases are frequent among patients with the obstructive sleep apnoea syndrome (OSAS), The aetiopathogenesis of this association is unclear. Type 1 plasminogen activator inhibitor (PAI-1) is one of the primary regulators of the fibrinolytic system. A reported association between PAI-1 activity and an insertion/deletion polymorphism (4G/5G) in the promoter region of the PAI-1 gene suggests a critical role for this genomic region in the pathogenesis of several cardiovascular diseases. In this study, we determined the prevalence of this polymorphism in patients with OSAS and in healthy control subjects. The 4G/5G polymorphism in the promoter region of the PAI-1 gene was determined in 78 male patients with severe OSAS (56 +/- 2 apnoeas per hour) and in 70 healthy male, non-smoker volunteers of similar age, without personal or familial history of cardiovascular disease. The frequency ofthe 4G/4G, 4G/5G and 5G/5G genotypes in patients with OSAS (18%, 62%, 19%, respectively) was not significantly different from that seen in healthy subjects (16%, 60%, 24% P=NS). These results show that the distribution of the 4G/5G polymorphism in the promoter region ofthe PAI-1 gene in patients with OSAS is similar to that observed in healthy subjects. This observation suggests that the PAI-1 polymorphism has no relationship with the increased risk of cardiovascular diseases seen in patients with OSAS.

Case-Control Studies↗

Partial atrioventricular canal defect in a dog.

A case of a partial atrial canal defect is described in a nine-month-old female English setter. The patient had a large ostium primum atrial septal defect and a concurrent malformation of the mitral valve. Electrocardiographic and radiographic findings were suggestive of marked enlargement of the right heart and pulmonary overcirculation. Definitive diagnosis and assessment of the haemodynamic consequences were made using echocardiography. The magnitude of the left-to-right intracardiac shunt was estimated by measuring the pulmonary to systemic flow ratio (Qp/Qs) from Doppler-derived pulmonary and aortic blood flow. The results of this report suggest that dogs with a partial atrioventricular canal defect and concurrent mild mitral regurgitation may exhibit no clinical signs during the first years of life, even in cases with a Qp/Qs ratio of greater than 2.

Animals↗

Urinary tract infection caused by Corynebacterium urealyticum in a dog.

Urinary tract infection (UTI) caused by Corynebacterium urealyticum is a rarely recognised condition in veterinary medicine. This report describes a case in a 13-month-old dog which presented with a history of dysuria and haematuria. C urealyticum was identified as the cause of UTI. The clinical, radiological and ultrasonographic features and the results of urinalysis and urine bacteriological culture are described, as are the therapeutic challenges presented by this particular infection.

Animals↗

Recruitment of the mitochondrial-dependent apoptotic pathway in amyotrophic lateral sclerosis.

Molecular mechanisms of apoptosis may participate in motor neuron degeneration produced by mutant superoxide dismutase-1 (mSOD1), the only proven cause of amyotrophic lateral sclerosis (ALS). Consistent with this, here we show that the proapoptotic protein Bax translocates from the cytosol to the mitochondria, whereas cytochrome c translocates from the mitochondria to the cytosol in spinal cords of transgenic mSOD1 mice during the progression of the disease. Concomitantly, caspase-9 is activated in the spinal cord of transgenic mSOD1 mice. Only in end-stage transgenic mSOD1 mice is the downstream caspase-7 activated and the inhibitor of apoptosis, XIAP, cleaved. These results indicate a sequential recruitment of molecular elements of the mitochondrial-dependent apoptotic pathway in transgenic mSOD1 mice. We also provide immunohistochemical evidence that cytochrome c translocation occurs in the spinal cord of sporadic ALS patients. Collectively, these data suggest that the mitochondrial-dependent apoptotic pathway may contribute to the demise of motor neurons in ALS and that targeting key molecules of this cascade may prove to be neuroprotective.

Amyotrophic Lateral Sclerosis↗

Bax ablation prevents dopaminergic neurodegeneration in the 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) damages dopaminergic neurons in the substantia nigra pars compacta (SNpc) as seen in Parkinson's disease. Here, we show that the pro-apoptotic protein Bax is highly expressed in the SNpc and that its ablation attenuates SNpc developmental neuronal apoptosis. In adult mice, there is an up-regulation of Bax in the SNpc after MPTP administration and a decrease in Bcl-2. These changes parallel MPTP-induced dopaminergic neurodegeneration. We also show that mutant mice lacking Bax are significantly more resistant to MPTP than their wild-type littermates. This study demonstrates that Bax plays a critical role in the MPTP neurotoxic process and suggests that targeting Bax may provide protective benefit in the treatment of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

LY293558, an AMPA glutamate receptor antagonist, prevents and reverses levodopa-induced motor alterations in Parkinsonian rats.

To evaluate the possible involvement of glutamate AMPA receptor-mediated mechanisms in levodopa-induced motor fluctuations, we investigated the effects of LY293558, a competitive AMPA receptor antagonist, on levodopa-induced motor alterations in rats with unilateral 6-OHDA lesion. Acute and chronic administration of LY293558 was studied to evaluate the possible reversion or prevention of these levodopa effects. In the first set of experiments, rats were treated with levodopa (25 mg/kg with benserazide, twice daily, i.p.) for 22 days and on day 23 LY293558 (5 mg/kg, i.p.) was administered immediately before levodopa. In the second set of experiments, rats were treated daily for 22 days with levodopa and LY293558 (5 mg/kg, twice daily, i.p.). In the third set of experiments, the effect of LY293558 (5 mg/kg, i.p.) administration on selective dopamine D-1 (SKF38393, 1.5 mg/kg, s.c.) and D-2 agonist (quinpirole, 0.1 mg/kg, i.p.)-induced rotational behavior after daily levodopa treatment was studied. The duration of the rotational behavior induced by chronic levodopa decreased by 30% after 22 days. Acute administration of LY293558 on day 23 reversed this effect. The group of animals that were chronically treated with levodopa and LY293558 did not show the decrease in this motor response duration. Chronic levodopa treatment attenuated the rotational response to the D-1 agonist SKF38393 and increased the response to the D-2 agonist quinpirole. LY293558 did not reverse the effect of levodopa on rotational behavior induced by the D-1 agonist but significantly reduced the rotational response to the D-2 agonist in levodopa-treated animals by 40%. Our results demonstrate that an AMPA receptor antagonist reverses and prevents levodopa-induced motor alterations in parkinsonian rats and that this effect on motor fluctuations induced by chronic levodopa is probably due to a modulation of the indirect output pathway of the basal ganglia.

Adrenergic Agents↗

Lack of nigral pathology in transgenic mice expressing human alpha-synuclein driven by the tyrosine hydroxylase promoter.

alpha-Synuclein has been identified as a major component of Lewy body inclusions, which are one of the pathologic hallmarks of idiopathic Parkinson's disease. Mutations in alpha-synuclein have been found to be responsible for rare familial cases of Parkinsonism. To test whether overexpression of human alpha-synuclein leads to inclusion formation and neuronal loss of dopaminergic cells in the substantia nigra, we made transgenic mice in which the expression of wild-type or mutant (A30P and A53T) human alpha-synuclein protein was driven by the promoter from the tyrosine hydroxylase gene. Even though high levels of human alpha-synuclein accumulated in dopaminergic cell bodies, Lewy-type-positive inclusions did not develop in the nigrostriatal system. In addition, the number of nigral neurons and the levels of striatal dopamine were unchanged relative to non-transgenic littermates, in mice up to one year of age. These findings suggest that overexpression of alpha-synuclein within nigrostriatal dopaminergic neurons is not in itself sufficient to cause aggregation into Lewy body-like inclusions, nor does it trigger overt neurodegenerative changes.

Animals↗

Engineered modeling and the secrets of Parkinson's disease.

The development of new methods for manipulating the animal genome by transgenic and gene-targeting technologies provides a unique means of studying the most intimate aspects of countless human diseases, including Parkinson's disease (PD). In this review, the contribution of such engineered models to our current understanding of the pathophysiology, etiology and pathogenesis of PD will be discussed.

Animals↗

Oxidative post-translational modifications of alpha-synuclein in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease.

Structural and functional alterations of alpha-synuclein is a presumed culprit in the demise of dopaminergic neurons in Parkinson's disease (PD). Alpha-synuclein mutations are found in familial but not in sporadic PD, raising the hypothesis that effects similar to those of familial PD-linked alpha-synuclein mutations may be achieved by oxidative post-translational modifications. Here, we show that wild-type alpha-synuclein is a selective target for nitration following peroxynitrite exposure of stably transfected HEK293 cells. Nitration of alpha-synuclein also occurs in the mouse striatum and ventral midbrain following administration of the parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Conversely, beta-synuclein and synaptophysin were not nitrated in MPTP-intoxicated mice. Our data demonstrate that alpha-synuclein is a target for tyrosine nitration, which, by disrupting its biophysical properties, may be relevant to the putative role of alpha-synuclein in the neurodegeneration associated with MPTP toxicity and with PD.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗