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Biomedical subjects

J Vidal

Publications and source records attributed to J Vidal.

At least 19 recordsLinked to original sources
PubMed2001

Phosphoenolpyruvate carboxylase kinase is controlled by a similar signaling cascade in CAM and C(4) plants.

In Crassulacean acid metabolism (CAM) plants, phosphoenolpyruvate carboxylase (PEPC) is subject to day-night regulatory phosphorylation of a conserved serine residue in the plant enzyme's N-terminal domain. The dark increase in PEPC-kinase (PEPC-k) activity is under control of a circadian oscillator, via the enhanced expression of the corresponding gene (1). The signaling cascade leading to PEPC-k up-regulation was investigated in leaves and mesophyll cell protoplasts of the facultative, salt-inducible CAM species, Mesembryanthemum crystallinum. Mesophyll cell protoplasts had the same PEPC-k activity as leaves from which they were prepared (i.e., high at night, low during the day). However, unlike C(4) protoplasts (2), CAM protoplasts did not show marked PEPC-k up-regulation when isolated during the day and treated with a weak base such as NH(4)Cl. Investigations using various pharmacological reagents established the operation, in the darkened CAM leaf, of a PEPC-k cascade including the following components: a phosphoinositide-dependent phospholipase C (PI-PLC), inositol 1,4,5 P (IP(3))-gated tonoplast calcium channels, and a putative Ca(2+)/calmodulin protein kinase. These results suggest that a similar signaling machinery is involved in both C(4) (2, 3) and CAM plants to regulate PEPC-k activity, the phosphorylation state of PEPC, and, thus, carbon flux through this enzyme during CAM photosynthesis.

Circadian Rhythm↗
PubMed2001

Intermittent treatment for malaria and anaemia control at time of routine vaccinations in Tanzanian infants: a randomised, placebo-controlled trial.

BACKGROUND: Clinical malaria and severe anaemia are major causes of paediatric hospital admission and death in many malaria-endemic settings. In the absence of an effective and affordable vaccine, control programmes continue to rely on case management while attempting the large-scale deployment of insecticide-treated nets. We did a randomised, placebo-controlled trial to assess the efficacy and safety of intermittent sulphadoxine-pyrimethamine treatment on the rate of malaria and severe anaemia in infants in a rural area of Tanzania. METHODS: We randomly assigned 701 children living in Ifakara, southern Tanzania, sulphadoxine-pyrimethamine or placebo at 2, 3, and 9 months of age. All children received iron supplementation between 2 and 6 months of age. The intervention was given alongside routine vaccinations delivered through WHO's Expanded Program on Immunisation (EPI). The primary outcome measures were first or only episode of clinical malaria, and severe anaemia in the period from recruitment to 1 year of age. Morbidity monitoring through a hospital-based passive case-detection system was complemented by cross-sectional surveys at 12 and 18 months of age. Results were expressed in terms of protective efficacy (100 [1-hazard ratio]%) and analysis was by intention to treat. FINDINGS: 40 children dropped out (16 died, 11 migrated, 12 parents withdrew consent, and one for other reasons). Intermittent sulphadoxine-pyrimethamine treatment was well tolerated and no drug-attributable adverse events were recorded. During the first year of life, the rate of clinical malaria (events per person-year at risk) was 0.15 in the sulphadoxine-pyrimethamine group versus 0.36 in the placebo group (protective efficacy 59% [95% CI 41-72]), and the rate of severe anaemia was 0.06 in the sulphadoxine-pyrimethamine group versus 0.11 in the placebo group (50% [8-73]). Serological responses to EPI vaccines were not affected by the intervention. INTERPRETATION: This new approach to malaria control reduced the rate of clinical malaria and severe anaemia by delivering an available and affordable drug through the existing EPI system. Data are urgently needed to assess the potential cost-effectiveness of intermittent treatment in areas with different patterns of malaria endemicity.

Anemia, Iron-Deficiency↗
PubMed2001

Community-based seroepidemiological survey of HCV infection in Catalonia, Spain.

The objective of this study was to investigate the prevalence of antibodies against the hepatitis C virus (anti-HCV) and the associated risk factors in a representative sample of the population of Catalonia, Spain. Serum samples from 2,142 subjects aged between 5 and 70 years, selected at random from urban and rural habitats, were studied. Multiple logistic regression analysis was carried out to determine variables associated independently with the presence of HCV antibodies. The age and gender standardized prevalence of anti-HCV was 2.5% (95% confidence interval, 1.8-3.2). Prevalence increased significantly with age (P < 0.001), but no other sociodemographic variables were associated with HCV infection. Tattoos (OR: 6.2), blood transfusions (OR: 5.0) intravenous drug use (OR: 4.9) and antecedents of hospitalization (OR: 2.3) were variables associated independently with infection. HCV infection affects mainly elderly people in Spain and spares children and adolescents. This suggests that major exposure to HCV may have occurred many years ago, when infection was more widespread than in recent years.

Adolescent↗
PubMed2001

Early imaging of integration response to polypropylene mesh in abdominal wall by environmental scanning electron microscopy: comparison of two placement techniques and correlation with tensiometric studies.

The repair of incisional hernias has taken advantage of the strength provided by prosthetic mesh grafts, but the best position for inserting the materials has not been conclusively established. Environmental scanning electron microscopy (ESEM) provides imaging of biologic samples with minimal manipulation. We used ESEM for early imaging of the integration response to polypropylene meshes placed in two anatomic positions in the abdominal wall and correlated results with tensiometric studies. Two macroporous polypropylene prostheses were implanted in a rat model--one on the abdominal aponeurotic layer and one on the peritoneal surface--without creating a wall defect. Studies were performed over implantation intervals of 7, 15, and 30 days in strips obtained from the polypropylene fiber-receptor repair tissue interface. Microscopic appearance, tensile strength, percent elongation, and stiffness were evaluated. Meshes implanted on the abdominal aponeurotic layer showed better early tissue incorporation (higher collagen deposition, capillary density, cell accumulation) and increased tensile strength, reflecting tighter anchorage to the abdominal wall. The percent elongation increased from day 7 to day 30 after implantation, mainly in the deep stratum. The ESEM images correlated well with biomechanical results, indicating the potential of this technique as a powerful, effective tool for use in wound-healing studies.

Abdominal Muscles↗
PubMed2001

Salt stress increases the Ca2+-independent phosphoenolpyruvate carboxylase kinase activity in Sorghum leaves.

In C4 plants, the photosynthetic enzyme phosphoenolpyruvate carboxylase (PEPCase; EC 4.1.1.31) is subjected to a phosphorylation process via the light-dependent up-regulation of a Ca2+-independent PEPCase-kinase. The present work aimed to study the effect of salt stress on PEPCase phosphorylation in Sorghum vulgare Pers. leaves. The growth of salt-treated plants was reduced compared with that of the control plants. PEPCase activity modestly increased (around 20-40%) whereas PEPCase phosphorylation was markedly enhanced, on a protein basis, in extracts from illuminated leaves. The enhanced protein kinase activity was found to display a low molecular mass in the range 32-35 kDa, to be independent of Ca2+ and to be up-regulated by light. Furthermore, up-regulation was blocked in vivo by the cytosolic protein synthesis inhibitor cycloheximide. Collectively, these data demonstrated that salinity stress altered the Ca2+-independent PEPCase-kinase, presumably by increasing the mesophyll content of the enzyme. Potassium chloride, but not abscisic acid, mimicked the effect of NaCl on PEPCase-kinase activity.

Abscisic Acid↗
PubMed2001

Imidazo[1,2-a]quinoxalines: synthesis and cyclic nucleotide phosphodiesterase inhibitory activity.

A group of imidazo[1,2-a]quinoxalines have been synthesised from quinoxaline by condensation of an appropriate haloester or intramolecular cyclisation of a keto moiety on an intracyclic nitrogen atom. The reactivity of the heterocycle was explored through diverse reactions such as electrophilic substitution, lithiation and halogen-metal exchange to give access to a new series of derivatives. Confirmation of their structure was mainly performed by NMR, after careful assignment of the signals in comparison to previous attributions made on the parent imidazo[1,2-a]quinoxaline and discussion of available data in the literature. The cyclic nucleotide phosphodiesterase inhibitor activity of some of these derivatives has been assessed on isoenzymes type III and type lV. Compound 15, 4-(methylamino)imidazo[1,2-a]quinoxaline-2-carbonitrile, exhibited potent relaxant activity on smooth muscle, with a potency similar to the one measured with SCA 40, its structural analogue in the imidazo[1,2-a]pyrazine series.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed2001

The seroepidemiology of B. pertussis infection in Catalonia, Spain.

A survey of the seroprevalence of pertussis antibodies in a representative sample of the population from Catalonia was carried out. Ninety-seven municipalities and 30 schools were randomly selected to recruit the 2126 subjects who participated in the study. A serum sample was obtained from all individuals participating in the study in order to determine levels of pertussis toxin (PT) and filamentous hemagglutinin (FHA) antibodies by ELISA test. Sociodemographic data were collected for all subjects. The prevalence of PT antibodies was 75% and that of FHA antibodies 89%. Significant increments were observed with age, both in the prevalence of PT (P < 0.0001) and of FHA (P = 0.018). Of the sociodemographic variables studied, only urban habitat was significantly associated to PT antibodies. The agreement observed among the two types of antibodies studied was weak (K = 0.264). Routine revaccination with the acellular vaccine in children over 7 years of age, in adolescents and adults seems a reasonable strategy to prevent the appearance of cases of pertussis in the community.

Adhesins, Bacterial↗
PubMed2001

Immunogenicity and reactogenicity of the adult tetanus-diphtheria vaccine. How many doses are necessary?

The immunogenicity and reactogenicity of the tetanus-diphtheria adult type vaccine was compared in two groups: group I (n = 201, 18-30 years old, presumably vaccinated with the DTP vaccine) and group II (n = 147, > or = 45 years old, without vaccination antecedents). Before vaccination, the seroprotection levels for tetanus were 90.5% (group I) and 30.6% (group II). These rose to 99.5% and 81.7%, respectively, after administration of one vaccine dose. For diphtheria, prevaccination seroprotection levels were 38.3% (group I) and 19.0% (group II). These rose to 85.8% and 65.7%, respectively, after vaccination. The logistic regression analysis showed an association between antibody titre and age. In group II, 3 doses of Td vaccine were needed to reach titres similar to those achieved in group I with a single dose. Stated reactogenicity was greater in: young subjects, women, those with higher titres of tetanus antibodies and those receiving other vaccines simultaneously. These results confirm the need for vaccination schedules adapted to the characteristics of each population age-group.

Adult↗
PubMed2001

Radioisotopic control for baclofen pump catheter failure.

STUDY DESIGN: Case report of Baclofen pump catheter failure investigated by radioisotope injection. OBJECTIVES: To report a safe and reliable method for evaluating catheter dysfunction. SETTING: France. METHODS: Single case report of failure of Baclofen pump investigated by radioisotope injection. RESULTS: The injection demonstrated the block in the catheter. The catheter failure was not visualised by plain X-ray nor by filling the pump with radio-opaque solution. CONCLUSION: Catheter failure is a common cause of intrathecal drug delivery problems and may be difficult to diagnose. When catheter disconnection, kink, or dislodgement is not visible on X-ray, radioisotopic control is a safe and reliable method for assessment.

Adult↗
PubMed2001

Efficacy, safety and predictive factors of therapeutic success with sildenafil for erectile dysfunction in patients with different spinal cord injuries.

STUDY DESIGN: Multicenter, open, prospective, before-after study. OBJECTIVE: To assess the efficacy and safety of sildenafil therapy for erectile dysfunction in patients with spinal cord injury, and the association between the response to sildenafil and factors such as causes and levels of spinal cord injury, grade of ASIA deficit, time since injury, orgasmic perception, and degree of baseline erection. SETTING: Homes of outpatients of 16 spinal cord injury units in Spain. METHOD: One hundred and seventy patients with erectile dysfunction secondary to spinal cord injury, from whom baseline data were collected on their sexual function, and who started treatment with sildenafil 50 mg. An efficacy assessment was made by the patient and his partner, and the score of the International Index of Erectile Function (IIEF) was recorded. RESULTS: It was reported by 88.2% of the patients and 85.3% of their partners that treatment with sildenafil had improved their erections, regardless of the baseline characteristics of the spinal cord injury and erectile function. In responders, this improvement was confirmed by an increase from 12.5 to 24.8 points (P<0.001) of the Erectile Function Domain of IIEF. A significant improvement was also seen in patients' satisfaction with sexual activity and general satisfaction derived from sexual life. Preservation of orgasmic perception and a baseline degree of erection of 3 or 4 (P=0.006) were predictors of therapeutic success. No serious adverse events occurred. CONCLUSION: Sildenafil is an effective, well-tolerated treatment for erectile dysfunction caused by spinal cord injury, regardless of the cause, neurological level, ASIA grade, and time since injury. SPONSORSHIP: Spanish Society of Paraplegia.

Adult↗
PubMed2001

Intrathecal baclofen after traumatic brain injury: early treatment using a new technique to prevent spasticity.

BACKGROUND: In the early course of severe head trauma, the clinical value of intrathecal administration of baclofen to reduce autonomic disorders and spasticity has not been established. METHODS: We studied four patients (Glasgow Coma Scale score 3 or 4) with autonomic disorders and spasticity who failed to respond to conventional treatment during the early course of head injury. Baclofen (25 microg/mL) was infused continuously through an intrathecal catheter inserted at patient bedside and subcutaneously tunneled. When this treatment was successful, the spinal catheter was removed and surgically replaced by another catheter connected to a subcutaneous pump. Clinical follow-up was obtained at 6 months after the head injury. RESULTS: Mean delay for the initiation of intrathecal baclofen was 25 days (range, 21 to 31 days), and optimal dose was 385 +/- 185 microg/day. In all patients, the Ashworth score was consistently reduced (3.5 +/- 0.5 vs. 4.5 +/- 0.5 for upper limbs and 2 +/- 0.5 vs. 4.5 +/- 0.5 for lower limbs), as were both the frequency and intensity of autonomic disorders. The spinal catheters were used during a mean period of 9.5 +/- 1.7 days without complications. All three survivors were equipped with a programmable pump and had a lower Ashworth score at 6 months. Autonomic disorders had disappeared in two patients and remained modest in the remaining patient. CONCLUSION: Continuous administration of baclofen via the intrathecal route using this new technique seems to reduce autonomic disorders and spasticity during the early course of severe traumatic head injury.

Adult↗
PubMed2001

Identification and functional analysis of mutations in FAD-binding domain of mitochondrial glycerophosphate dehydrogenase in caucasian patients with type 2 diabetes mellitus.

Ca2+-responsive mitochondrial FAD-linked glycerophosphate dehydrogenase (mGPDH) is a key component of the pancreatic beta-cell glucose-sensing device. The purpose of this study was to examine the association of mutations in the cDNA coding for the FAD-binding domain of mGPDH and to explore the functional consequences of these mutations in vitro. To investigate this association in type 2 diabetes mellitus, we studied a cohort of 168 patients with type 2 diabetes and 179 glucose-tolerant control subjects of Spanish Caucasian origin by single-stranded conformational polymorphism analysis. In vitro site-directed mutagenesis was performed in the mGPDH cDNA sequence to reproduce those mutations that produce amino acid changes in a patient with type 2 diabetes. We detected mutations in the mGPDH FAD-binding domain in a single patient, resulting in a Gly to Arg amino acid change at positions 77, 78, and 81 and a Thr to Pro at position 90. In vitro expression of the mutated constructs in Xenopus oocytes resulted in a significantly lower enzymatic activity than in cells expressing the wild-type form of the enzyme. Our results indicate that although mutations in the mGPDH gene do not appear to have a major role in type 2 diabetes mellitus, the reduction in mGPDH enzymatic activity associated with the newly described mGPDH mutations suggests that they may contribute to the disease in some patients.

Aged↗
PubMed2001

Islet amyloid develops diffusely throughout the pancreas before becoming severe and replacing endocrine cells.

Islet amyloid occurs in >90% of type 2 diabetic patients and may play a role in the pathogenesis of this disease. To determine whether islet amyloid occurs diffusely throughout the pancreas, whether it affects islets equally, and whether it decreases islet endocrine cells, we characterized islet amyloidosis by computerized fluorescence microscopy in transgenic mice that develop typical islet amyloid. These mice produce the unique amyloidogenic component of human islet amyloid, human islet amyloid polypeptide (hIAPP). The prevalence of amyloid (number of islets containing amyloid/total number of islets x 100) and the severity of amyloid (Sigmaamyloid area/Sigmaislet area x 100) were found to be uniform throughout the pancreas. Furthermore, a high prevalence of amyloid was observed in islets when the severity of amyloid was only 1.5% of the islet area, suggesting a diffuse distribution of amyloid from the very early stages of islet amyloidosis. In 12 hIAPP transgenic mice with an amyloid severity of 9.6 +/- 3.4%, the proportion of islets composed of beta- and delta-cells was reduced in the transgenic mice compared with 6 nontransgenic mice that do not develop amyloid (beta-cells: 62.9 +/- 3.1% vs. 75.5 +/- 0.9%, P = 0.02; delta-cells: 2.8 +/- 0.5% vs. 4.4 +/- 0.4%, P = 0.05), whereas the proportion of islets composed of alpha-cells did not significantly differ between the two groups of mice. In the individual islets in these transgenic mice, amyloid severity was inversely correlated with beta-cell, (r = -0.59, P < 0.0001), alpha-cell (r = -0.32, P < 0.0001), and delta-cell (r = -0.25, P < 0.0001) areas. In conclusion, islet amyloidosis occurs uniformly throughout the pancreas, affecting all islets before becoming severe. A reduction in islet endocrine mass starts at this early stage of islet amyloid development and progresses as amyloid mass increases.

Amyloid↗
PubMed2000

Interaction induced delocalization for two particles in a periodic potential

We consider two interacting particles evolving in a one-dimensional periodic structure embedded in a magnetic field. We show that the strong localization induced by the magnetic field for particular values of the flux per unit cell is destroyed as soon as the particles interact. We study the spectral and dynamical aspects of this transition.

Journal Article↗
PubMed2000

A DNA-binding activity for the promoter of the gene encoding C(4) phosphoenolpyruvate carboxylase is modulated by phosphorylation during greening of the Sorghum leaf.

Electrophoresis mobility shift assay (EMSA) identified nuclear proteins with binding activity to a 430 bp promoter fragment of the Sorghum C(4) phosphoenolpyruvate carboxylase gene (SvC4). The DNA binding activities (two main retarded bands; PC1 and PC2) were high in nuclear extracts from etiolated leaves, decreased during greening and became very low or null in nuclear extracts from green leaves. This process was found to be mediated by phytochrome and was apparently irreversible since the DNA-binding activities were not restored in green plants kept in continuous darkness. The AT-rich region of the promoter fragment was identified to be the interaction domain of PC2. The detection of PC2 with EMSA was markedly reduced by preincubation of nuclear protein extracts with Mg-ATP or Mg-GTP and restored in the presence of a general protein serine/threonine-kinase inhibitor, K252a. The results suggested that the PC2 binding activity was modulated by phosphorylation during the greening process of the Sorghum leaf.

Journal Article↗