Sérgio Marques - Academia.edu (original) (raw)

Papers by Sérgio Marques

Research paper thumbnail of Endoscopic Sphincterotomy Before Deployment of Covered Metal Stent is Associated With Greater Complication Rate: A Prospective Randomized Control Trial

Journal of Clinical Gastroenterology, 2008

Endoscopic sphincterotomy (ES) may facilitate insertion of self expandable metal stent (SEMS) and... more Endoscopic sphincterotomy (ES) may facilitate insertion of self expandable metal stent (SEMS) and also help avert the development of pancreatitis from stent-related occlusion of the pancreatic duct. On the other hand, ES is also independently associated with pancreatitis, bleeding, and perforation. We evaluated whether ES before SEMS placement was associated with a greater likelihood of stent migration and other complications in patients with malignant obstruction of the distal common bile duct. Seventy-four patients with unresectable distal bile duct obstruction were prospectively randomized to biliary stenting following ES (group 1) and without ES (group 2). Main outcome measures included overall procedure complications rates including stent migration, stent occlusion, oxygen desaturation, bleeding, perforation, and pancreatitis. Covered SEMS were successfully deployed in all patients in both groups. Stent migration occurred in 6 patients (16%) in group 1 and 1 patient (3%) in group 2, P=0.075. Overall, complications occurred in 18 patients in group 1 and 4 patients in group 2, P=0.006. There was no pancreatitis in either group. Deployment of covered SEMS without prior ES in patients with distal common bile duct obstruction owing to pancreatic cancer is feasible and prevents the development of complications such as stent migration, bleeding, and perforation.

Research paper thumbnail of Helicobacter pylori cag pathogenicity island genes: clinical relevance for peptic ulcer disease development in Brazil

Journal of Medical Microbiology, 2007

cag pathogenicity island (PAI) integrity was investigated in isolates from multiple biopsies reco... more cag pathogenicity island (PAI) integrity was investigated in isolates from multiple biopsies recovered from 40 patients in an attempt to determine the co-existence of a varying cagPAIpositive to cagPAI-negative ratio in a single host. Six biopsies were obtained from each patient during the same endoscopic session. cagPAI analysis included amplification of seven loci (cagA, cagE, cagG, cagM, cagT, HP0527 and HP0524) and the left end of cagII (LEC). Absence of the island was confirmed by empty-site PCR. lspA-glmM RFLP and random amplified polymorphic DNA PCR were used for strain delineation. The number of biopsies with Helicobacter pylori-positive culture ranged from three to six per patient and a total of 218 isolates were recovered. Mixed infection was only found in two patients. Nearly one-third of the 40 patients harboured isolates with an intact cagPAI in all niches, another third of the isolates were empty-site-positive in all niches, whilst the remaining third of the isolates had a disrupted cagPAI in all or at least one of the niches. Co-existence of variants of the same strain with different cagPAI genotypes was observed in one-quarter of patients. The variations in cagPAI genotype included co-existence of: diverse cagPAI deletions in different niches, variants with intact and with partially deleted islands, variants with empty-site-positive and with partially deleted cagPAIs, and variants with an intact cagPAI and with empty-site-positive. Half of the patients with different cagPAI genotypes harboured an intact cagPAI in at least one niche. Co-existence of diverse genotypes of putative virulence factors in a single host must be considered when drawing a correlation with clinical presentation.

Research paper thumbnail of Effect of paratuberculosis on the diagnosis of bovine tuberculosis in a cattle herd with a mixed infection using interferon-gamma detection assay

Veterinary Microbiology, 2009

Interferon-gamma (IFN-γ) detection assay is being applied as an ancillary test to tuberculin test... more Interferon-gamma (IFN-γ) detection assay is being applied as an ancillary test to tuberculin tests in the diagnosis of bovine tuberculosis to detect the maximum number of infected animals. Among possible factors influencing the performance of tuberculosis-diagnostic tests, paratuberculosis, a widespread disease in Spain and other European countries, has been pointed out as a cause of false positive reactions. Still, its effect on the sensitivity of these tests in cattle has yet to be fully characterized. The impact of paratuberculosis in the apparent sensitivity of IFN-γ assay was studied in a bullfighting cattle herd with a mixed tuberculosis–paratuberculosis infection, using culture of Mycobacterium bovis and Mycobacterium avium paratuberculosis as the gold standard to determine the infection status of every animal. A total of 218 animals were slaughtered and sampled for bacteriology after blood sampling. IFN-γ assay showed a lower apparent sensitivity in animals with a mixed infection (50%) compared to all animals suffering tuberculosis (78.3%). This finding indicates that the presence of paratuberculosis in tuberculosis-infected herds could imply a serious impairment in the sensitivity of IFN-γ detection test.

Research paper thumbnail of Infrared Spectra of Inorganic Hydrogen Bond Complexes of Pyridoxine

Spectroscopy Letters, 1996

Research paper thumbnail of Um programa baseado na triagem visual de recém-nascidos em maternidades: Fundação Altino Ventura/2000

Arquivos Brasileiros De Oftalmologia, 2002

Research paper thumbnail of Morphological analysis of the vestibular aqueduct by computerized tomography images

European Journal of Radiology, 2007

In the last two decades, advances in the computerized tomography (CT) field revise the internal a... more In the last two decades, advances in the computerized tomography (CT) field revise the internal and medium ear evaluation. Therefore, the aim of this study is to analyze the morphology and morphometric aspects of the vestibular aqueduct on the basis of computerized tomography images (CTI).Computerized tomography images of vestibular aqueducts were acquired from patients (n = 110) with an age range of 1–92 years. Thereafter, from the vestibular aqueducts images a morphometric analysis was performed. Through a computerized image processing system, the vestibular aqueduct measurements comprised of its area, external opening, length and the distance from the vestibular aqueduct to the internal acoustic meatus.The morphology of the vestibular aqueduct may be funnel-shaped, filiform or tubular and the respective proportions were found to be at 44%, 33% and 22% in children and 21.7%, 53.3% and 25% in adults. The morphometric data showed to be of 4.86 mm2 of area, 2.24 mm of the external opening, 4.73 mm of length and 11.88 mm of the distance from the vestibular aqueduct to the internal acoustic meatus, in children, and in adults it was of 4.93 mm2, 2.09 mm, 4.44 mm, and 11.35 mm, respectively.Computerized tomography showed that the vestibular aqueduct presents high morphological variability. The morphometric analysis showed that the differences found between groups of children and adults or between groups of both genders were not statistically significant.

Research paper thumbnail of Morphometric Analysis of the Internal Auditory Canal by Computed Tomography Imaging

Iranian Journal of Radiology, 2012

Many clinical and experimental studies have been done to analyze the anatomical and functional as... more Many clinical and experimental studies have been done to analyze the anatomical and functional aspects of the internal auditory canal (IAC) in human beings since there are great inter-individual variability and structural variations that may occur regarding the other adjacent structures. Objectives: The purpose of this study was to characterize the morphology of the internal auditory canal (IAC) during development using high resolution computed tomography (CT) and to analyze its dimensions, which will be determined by measuring the nearby areas and structures using a system of digital image processing. Patients and Methods: CT images of the IAC of 110 normal subjects aged 1 to 92 years (mean age, 46.5 years) of both genders were reviewed to determine the shape, area, opening width (OW), longitudinal length (LL), vertical diameter (VD) and distance from the vestibular aqueduct. Results: The shapes observed in children and adults were funnel-shaped (74% and 58.3%, respectively), cylindrical (22% and 30.9%, respectively) and bud-shaped (4% and 10.8%, respectively). The measurements by CT in children were: area= 50.30 mm 2 , OW = 7.53 mm, length = 11.17 mm, VD = 4.82 mm and the distance between the IAC and the vestibular aqueduct (VA) = 12.63 mm. In adults, the measurements were: area = 44.64 mm 2 , OW = 7.10 mm, length = 9.84 mm, VD = 4.47 mm and the distance between IAC and VA = 11.17 mm. Conclusions: CT images showed that the IAC has different shapes and when the measurements obtained for children were compared with those of adults, the parameters that presented statistically significant differences in either gender were length and diameter.

Research paper thumbnail of The External Opening of the Cochlear Aqueduct in Infants and Adults

Oto-Rhino-Laryngologia Nova, 2001

The purpose of the present study is the description of the shape and area of the cochlear aqueduc... more The purpose of the present study is the description of the shape and area of the cochlear aqueduct (CA) opening by means of molds obtained from infant and adult temporal bones. Material and Methods: Through molding techniques the evaluation was performed in 118 temporal bones of infants (5-60 months) and of adults (19-89 years), dimensions and shapes being evaluated through computerized image processing. Results and Conclusions: The data shows that the area of the opening is significantly smaller in children than in adults (7.32 B 3.32 versus 18.48 B 6.42 mm 2 ). In infants, in 56% the shape of the opening was triangular; in adults triangularity was 100%. The variability in the shape and size of the CA opening in infants suggests adaptations of the CA opening during cranial growth.

Research paper thumbnail of The External Opening of the Cochlear Aqueduct in Infants and Adults

Oto-rhino-laryngologia Nova, 2001

The purpose of the present study is the description of the shape and area of the cochlear aqueduc... more The purpose of the present study is the description of the shape and area of the cochlear aqueduct (CA) opening by means of molds obtained from infant and adult temporal bones. Material and Methods: Through molding techniques the evaluation was performed in 118 temporal bones of infants (5-60 months) and of adults (19-89 years), dimensions and shapes being evaluated through computerized image processing. Results and Conclusions: The data shows that the area of the opening is significantly smaller in children than in adults (7.32 B 3.32 versus 18.48 B 6.42 mm 2 ). In infants, in 56% the shape of the opening was triangular; in adults triangularity was 100%. The variability in the shape and size of the CA opening in infants suggests adaptations of the CA opening during cranial growth.

Research paper thumbnail of Anatomical Variation of the Brachiocephalic Trunk and Common Carotid Artery in Neck Dissection

International Journal of Morphology, 2009

SUMMARY: Variations in the trajectory of the brachiocephalic trunk and the common carotid artery ... more SUMMARY: Variations in the trajectory of the brachiocephalic trunk and the common carotid artery predispose to disorders which might be critical in a tracheotomy and/or surgeries. Dissection of 110 formol fixed adult cadavers, both sexes, were performed to increase the anatomic ...

Research paper thumbnail of N-Carboxyalkyl derivatives of 3-hydroxy-4-pyridinones: synthesis, complexation with Fe(III), Al(III) and Ga(III) and in vivo evaluation

Journal of inorganic biochemistry, Jan 30, 2002

Research paper thumbnail of N-Arylamine derivatives of 3-hydroxy-4-pyridinones: solution studies and bioevaluation in view of Al-detoxification roles

Analytical and bioanalytical chemistry, 2005

A study of a series of bifunctional 3-hydroxy-4pyridinone derivatives, containing side-chains wit... more A study of a series of bifunctional 3-hydroxy-4pyridinone derivatives, containing side-chains with various alkyl-aryl-amine-amides as extra-functional groups, was conducted to assess the relevance of those groups to the Al-chelating affinity, the lipo-hydrophilic balance of the compounds, and 67 Ga biodistribution in mice, in view of their potential use as Al-decorporating agents; the results were compared with those for the drug Deferriprone. Their acid-base properties and Al-chelating affinity in aqueous solution were studied by potentiometric techniques. These ligands form very stable trischelated Al complexes and the non-chelating extragroups are only responsible for small differences in the complex stability (DpAl £ 1.2). At physiological pH the major ligand/complex species have different charges, because of the different extent of protonation of the ligands. The introduction of the different groups induces a well-balanced stepwise-like lipo-hydrophilic character (À0.2<log D oct./water <+1.1). The effect of each ligand on the biodistribution of 67 Ga in overloaded mice is rapid blood clearance for all of them, but with different biodistribution patterns, namely excretion pathways and brain uptake/clearance, thus suggesting potential different clinical use.

Research paper thumbnail of Effects of a uranium mine effluent in the early-life stages of Rana perezi Seoane

Science of The Total Environment, 2008

Amphibians have been reported as sensitive organisms whose survival has been impaired by several ... more Amphibians have been reported as sensitive organisms whose survival has been impaired by several environmental factors. Nevertheless, sometimes amphibians are found inhabiting extreme environments. Thus, in order to perceive how Iberian green frogs (Rana perezi Seoane) are able to survive in the ponds of a uranium mine (Central Portugal) this study aimed to assess the ecotoxicological effects promoted by the mine effluent in the early-life stages of this species. To attain this objective, eggs (collected in a nearby reference river) and laboratory hatching larvae were exposed during 96 h to different dilutions of the effluent. All the effects on the hatch success were recorded. The highest concentration of the effluent produced a significant decrease in body length of larvae, as well as a decrease in stimulus reactions and an increase in pigmentation along with tail deformities. A recovery assay showed an increased bioaccumulation of metals, uranium included, resulting from increased effluent exposure.

Research paper thumbnail of Iminodiacetyl-hydroxamate derivatives as metalloproteinase inhibitors: equilibrium complexation studies with Cu(II), Zn(II) and Ni(II)

Journal of Inorganic Biochemistry, 2003

Two new iminodiacetyl-hydroxamate derivatives, the N-benzyl-N-carboxymethyl-iminoacetohydroxamic ... more Two new iminodiacetyl-hydroxamate derivatives, the N-benzyl-N-carboxymethyl-iminoacetohydroxamic acid (H(2)L(1)) and the N-benzyl-N&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-hydroxypiperazine-2,6-dione (HL(2)), have been recently reported as very effective inhibitors against a set of zinc-containing matrix metalloproteinases (MMPs). Herein, aimed at understanding that inhibitory function, these compounds are studied in their complex formation equilibria with three biologically relevant first-row transition M(2+) metal ions (M=Cu, Zn, Ni) by using potentiometric and spectroscopic techniques. At physiological conditions, complexation of these metal ions by H(2)L(1) mostly occurs with formation of 1:1 species by tridentate co-ordination (O,N,N) (carboxylate-amino-hydroxamate), whereas complexation with HL(2) mainly involves the formation of 1:2 (M:L) species with normal (O,O) hydroxamate coordination. Moreover, at higher pH, H(2)L(1) is able to form a pentanuclear tetrameric copper complex with an interesting 12-metallacrown-4 structure.

Research paper thumbnail of Zinc(II) Complexation Behaviour of Sulfonamide-Based Enzyme Inhibitors

European Journal of Inorganic Chemistry, 2006

Sulfonamide derivatives containing extrafunctional groups, such as hydroxamic acids, hydroxypyrim... more Sulfonamide derivatives containing extrafunctional groups, such as hydroxamic acids, hydroxypyrimidinones and carboxylic acids, have been recently identified as inhibitors towards several zinc-containing enzymes, such as the matrix metalloproteinases (MMPs) and/or carbonic anhydrases (CAs). Since these inhibitors are supposed to bind the zinc ion at the active site, it was decided to study the zinc(II) complexation with a set of representative compounds in order to identify the most probable coordination modes and to find eventual relationships with the inhibitory properties. These studies were performed in aqueous solution, by potentiometry and 1H NMR spectroscopy, and in the solid phase, by infrared spectroscopy. The solution equilibrium studies indicate that these compounds present similar affinity for zinc (pZn ≈ 6). Under stoichiometric conditions, the formation of 1:1 metal complex species involves a preferential (O,O) coordination via the hydroxamic or hydroxypyrimidinone moieties, while the coordination via the sulfonamide groups could mainly be achieved under zinc excess conditions.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Research paper thumbnail of Protease Inhibitors: Synthesis of Bacterial Collagenase and Matrix Metalloproteinase Inhibitors Incorporating Succinyl Hydroxamate and Iminodiacetic Acid Hydroxamate Moieties

Journal of Enzyme Inhibition and Medicinal Chemistry, 2003

Novel matrix metalloproteinase (MMP)/bacterial collagenase inhibitors are reported, considering t... more Novel matrix metalloproteinase (MMP)/bacterial collagenase inhibitors are reported, considering the sulfonylated amino acid hydroxamates as lead molecules. A series of compounds was prepared by reaction of arylsulfonyl isocyanates with N-(5H-dibenzo[a,d]cyclohepten-5-yl)-and N-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yl) methyl glycocolate, respectively, followed by the conversion of the COOMe to the carboxylate/hydroxamate moieties. The corresponding derivatives with methylene and ethylene spacers between the polycyclic moiety and the amino acid functionality were also obtained by related synthetic strategies. These new compounds were assayed as inhibitors of MMP-1, MMP-2, MMP-8 and MMP-9, and of the collagenase isolated from Clostridium histolyticum (ChC). Some of the new derivatives reported here proved to be powerful inhibitors of the four MMPs mentioned above and of ChC, with activities in the low nanomolar range for some of the target enzymes, depending on the substitution pattern at the sulfonylureido moiety and on the length of the spacer through which the dibenzosuberenyl/suberyl group is connected with the rest of the molecule. Several of these inhibitors also showed selectivity for the deep pocket enzymes (MMP-2, MMP-8 and MMP-9) over the shallow pocket ones MMP-1 and ChC. #

Research paper thumbnail of Comparison of portuguese soils from different geographical regions using physicochemical, biological and biochemical parameters

Journal of Soils and Sediments, 2008

Background, Aim and Scope As a way of getting a comprehensive assessment of soil quality it is ne... more Background, Aim and Scope As a way of getting a comprehensive assessment of soil quality it is necessary to gather information on several appropriate soil parameters as well as also to perceive their spatial variation between geographic regions. The present work aimed to characterize and compare soil samples from different geographical regions and vegetation covers in the Portuguese territory through the use of physicochemical, biological and biochemical parameters. The study also intended to ascertain if those parameters are sensitive tools that consistently respond to geographical variations. Methodology Physical and chemical (soil organic matter contents, moisture, pH and conductivity), biological (macroarthropod es and diversity) and biochemical (potential nitrification, dehydrogenase and acid phosphatase activities) soil parameters were determined for three different regions of Portugal. Several sub-areas were chosen within each region, in order to include main vegetation patches. At each sampling sub-area, 5 traps were randomly set up for the collection of macroarthropods. For each sampling location, diversity descriptors of soil macrofauna were calculated: species richness, β diversity, the Shannon diversity (H′) and Pielou evenness (J′) indices. A principal component analysis (PCA) was used to plot the different sampling locations based on physical and chemical parameters; a canonical correspondence analysis (CCA) was performed to analyse the relationships between soil fauna and environmental variables (physicochemical parameters and enzyme activities) and a partial canonical correspondence analysis (pCCA), with vegetation patches as covariables, was carried out to perceive their contribution to the variation in macroarthropod distribution. Results Physical and chemical parameters discriminated soils from the different geographic regions in the PCA. Nevertheless, a CCA of environmental variables (physical and chemical properties, dehydrogenase activity, acid phosphatase activity and potential nitrification) and soil macroarthropod catches only discriminated continental soils (Arouca and S. Domingos Mine) from insular ones (Porto Santo Island). The former were correlated with high dehydrogenase activity (DHA) and potential nitrification values, while soils from the Porto Santo Island were particularly correlated with high pH values and low moisture percentages. However, in spite of the extreme conditions, Porto Santo sampling sub-areas presented a great diversity of macroarthropods, especially when compared to the S. Domingos Mine. The pCCA showed that the different vegetation patches only explained 15% of the variation in edaphic species distribution. Discussion Even though physical and chemical parameters were sufficient to discriminate the different geographical regions included in this study, biochemical and biological parameters grouped continental regions, discriminating them from the insular one. According to the CCA triplot, it was evident that the sampling sub-areas from the island were negatively correlated with soil moisture, suggesting that this was probably the main factor for the suppression of the microbial parameters in the island. On the other hand, the location of the S. Domingos mine area, in a metallogenetic province — the Iberian Pyrite Belt — may have contributed to the dominance of taxa more adapted to higher background levels of heavy metals. Conclusions In order to perceive geographical variation among different regions, more information is needed regarding different vegetation covers and the chemical composition of their corresponding litter, as well as about other soil chemical parameters. Recommendations and Perspectives The data gathered in this study will help to distinguish variation in soil biological and biochemical parameters induced by abiotic conditions from the one promoted by anthropogenic disturbances.

Research paper thumbnail of Design, synthesis and molecular modeling study of iminodiacetyl monohydroxamic acid derivatives as MMP inhibitors

Bioorganic & Medicinal Chemistry, 2006

As the matrix metalloproteinases (MMPs) can be massively up-regulated in degenerative tissues and... more As the matrix metalloproteinases (MMPs) can be massively up-regulated in degenerative tissues and degrade the extracellular matrix, these key enzymes are promising targets for the therapy of cancer and other degenerative diseases. Here, we are presenting a series of new non-peptidic hydroxamate-based matrix metalloproteinase inhibitors, MMPIs, incorporating the iminodiacetic (IDA) hydroxamic acid scaffold, as mimics of truncated peptidic MMPIs. A series of alkylaryl and sulfonylaryl groups, on the IDA basic scaffold, was investigated with the aim of improving potency and selectivity against MMPs involved in degenerative diseases. The sulfonamide based IDA derivatives studied (compounds B1–B3) showed to be potent (nM range) against deep S1′ pocket MMPs enzymes (i.e., MMP-2).We present the design, synthesis and docking studies on a series of new non-peptidic hydroxamate-based matrix metalloproteinase inhibitors, incorporating the iminodiacetic hydroxamic acid scaffolds.

Research paper thumbnail of Alkylaryl-amino derivatives of 3-hydroxy-4-pyridinones as aluminium chelating agents with potential clinical application

Journal of Inorganic Biochemistry, 2003

The neurotoxicity of aluminium is well established and so strategies for suitable aluminium chela... more The neurotoxicity of aluminium is well established and so strategies for suitable aluminium chelating therapies, aimed at the treatment and/or amelioration of some neurological disorders, are of current interest. The present work describes a set of new bifunctional compounds containing a 3-hydroxy-4-pyridinone (3,4-HP) unit, as the aluminium chelating moiety, which is extra-functionalised with different alkyl-arylamine molecular segments, to account for the improvement on the biodistribution specificity of the chelating agents or the corresponding complexes. Besides the synthetic scheme, studies are performed to assess the properties of these compounds, namely in terms of lipophilicity, Al-chelating ability, speciation and in vivo 67Ga biodistribution. These studies show that the extrafunctional groups fortunately have small effects on the high Al chelating affinity of the 3,4-HP units, over a wide range of pH, but they lead to favourable changes on the lipo-hydrophilic balance of the ligands and on the complex speciation. Differences found in the biodistribution, namely the decrease of the blood-clearance rate and increase of the bone retention or the hepatobiliary excretion, seem to be mostly rationalized in terms of the increasing lipophilic character of the ligands.

Research paper thumbnail of N-Carboxyalkyl derivatives of 3-hydroxy-4-pyridinones: synthesis, complexation with Fe(III), Al(III) and Ga(III) and in vivo evaluation

Journal of Inorganic Biochemistry, 2002

Research paper thumbnail of Endoscopic Sphincterotomy Before Deployment of Covered Metal Stent is Associated With Greater Complication Rate: A Prospective Randomized Control Trial

Journal of Clinical Gastroenterology, 2008

Endoscopic sphincterotomy (ES) may facilitate insertion of self expandable metal stent (SEMS) and... more Endoscopic sphincterotomy (ES) may facilitate insertion of self expandable metal stent (SEMS) and also help avert the development of pancreatitis from stent-related occlusion of the pancreatic duct. On the other hand, ES is also independently associated with pancreatitis, bleeding, and perforation. We evaluated whether ES before SEMS placement was associated with a greater likelihood of stent migration and other complications in patients with malignant obstruction of the distal common bile duct. Seventy-four patients with unresectable distal bile duct obstruction were prospectively randomized to biliary stenting following ES (group 1) and without ES (group 2). Main outcome measures included overall procedure complications rates including stent migration, stent occlusion, oxygen desaturation, bleeding, perforation, and pancreatitis. Covered SEMS were successfully deployed in all patients in both groups. Stent migration occurred in 6 patients (16%) in group 1 and 1 patient (3%) in group 2, P=0.075. Overall, complications occurred in 18 patients in group 1 and 4 patients in group 2, P=0.006. There was no pancreatitis in either group. Deployment of covered SEMS without prior ES in patients with distal common bile duct obstruction owing to pancreatic cancer is feasible and prevents the development of complications such as stent migration, bleeding, and perforation.

Research paper thumbnail of Helicobacter pylori cag pathogenicity island genes: clinical relevance for peptic ulcer disease development in Brazil

Journal of Medical Microbiology, 2007

cag pathogenicity island (PAI) integrity was investigated in isolates from multiple biopsies reco... more cag pathogenicity island (PAI) integrity was investigated in isolates from multiple biopsies recovered from 40 patients in an attempt to determine the co-existence of a varying cagPAIpositive to cagPAI-negative ratio in a single host. Six biopsies were obtained from each patient during the same endoscopic session. cagPAI analysis included amplification of seven loci (cagA, cagE, cagG, cagM, cagT, HP0527 and HP0524) and the left end of cagII (LEC). Absence of the island was confirmed by empty-site PCR. lspA-glmM RFLP and random amplified polymorphic DNA PCR were used for strain delineation. The number of biopsies with Helicobacter pylori-positive culture ranged from three to six per patient and a total of 218 isolates were recovered. Mixed infection was only found in two patients. Nearly one-third of the 40 patients harboured isolates with an intact cagPAI in all niches, another third of the isolates were empty-site-positive in all niches, whilst the remaining third of the isolates had a disrupted cagPAI in all or at least one of the niches. Co-existence of variants of the same strain with different cagPAI genotypes was observed in one-quarter of patients. The variations in cagPAI genotype included co-existence of: diverse cagPAI deletions in different niches, variants with intact and with partially deleted islands, variants with empty-site-positive and with partially deleted cagPAIs, and variants with an intact cagPAI and with empty-site-positive. Half of the patients with different cagPAI genotypes harboured an intact cagPAI in at least one niche. Co-existence of diverse genotypes of putative virulence factors in a single host must be considered when drawing a correlation with clinical presentation.

Research paper thumbnail of Effect of paratuberculosis on the diagnosis of bovine tuberculosis in a cattle herd with a mixed infection using interferon-gamma detection assay

Veterinary Microbiology, 2009

Interferon-gamma (IFN-γ) detection assay is being applied as an ancillary test to tuberculin test... more Interferon-gamma (IFN-γ) detection assay is being applied as an ancillary test to tuberculin tests in the diagnosis of bovine tuberculosis to detect the maximum number of infected animals. Among possible factors influencing the performance of tuberculosis-diagnostic tests, paratuberculosis, a widespread disease in Spain and other European countries, has been pointed out as a cause of false positive reactions. Still, its effect on the sensitivity of these tests in cattle has yet to be fully characterized. The impact of paratuberculosis in the apparent sensitivity of IFN-γ assay was studied in a bullfighting cattle herd with a mixed tuberculosis–paratuberculosis infection, using culture of Mycobacterium bovis and Mycobacterium avium paratuberculosis as the gold standard to determine the infection status of every animal. A total of 218 animals were slaughtered and sampled for bacteriology after blood sampling. IFN-γ assay showed a lower apparent sensitivity in animals with a mixed infection (50%) compared to all animals suffering tuberculosis (78.3%). This finding indicates that the presence of paratuberculosis in tuberculosis-infected herds could imply a serious impairment in the sensitivity of IFN-γ detection test.

Research paper thumbnail of Infrared Spectra of Inorganic Hydrogen Bond Complexes of Pyridoxine

Spectroscopy Letters, 1996

Research paper thumbnail of Um programa baseado na triagem visual de recém-nascidos em maternidades: Fundação Altino Ventura/2000

Arquivos Brasileiros De Oftalmologia, 2002

Research paper thumbnail of Morphological analysis of the vestibular aqueduct by computerized tomography images

European Journal of Radiology, 2007

In the last two decades, advances in the computerized tomography (CT) field revise the internal a... more In the last two decades, advances in the computerized tomography (CT) field revise the internal and medium ear evaluation. Therefore, the aim of this study is to analyze the morphology and morphometric aspects of the vestibular aqueduct on the basis of computerized tomography images (CTI).Computerized tomography images of vestibular aqueducts were acquired from patients (n = 110) with an age range of 1–92 years. Thereafter, from the vestibular aqueducts images a morphometric analysis was performed. Through a computerized image processing system, the vestibular aqueduct measurements comprised of its area, external opening, length and the distance from the vestibular aqueduct to the internal acoustic meatus.The morphology of the vestibular aqueduct may be funnel-shaped, filiform or tubular and the respective proportions were found to be at 44%, 33% and 22% in children and 21.7%, 53.3% and 25% in adults. The morphometric data showed to be of 4.86 mm2 of area, 2.24 mm of the external opening, 4.73 mm of length and 11.88 mm of the distance from the vestibular aqueduct to the internal acoustic meatus, in children, and in adults it was of 4.93 mm2, 2.09 mm, 4.44 mm, and 11.35 mm, respectively.Computerized tomography showed that the vestibular aqueduct presents high morphological variability. The morphometric analysis showed that the differences found between groups of children and adults or between groups of both genders were not statistically significant.

Research paper thumbnail of Morphometric Analysis of the Internal Auditory Canal by Computed Tomography Imaging

Iranian Journal of Radiology, 2012

Many clinical and experimental studies have been done to analyze the anatomical and functional as... more Many clinical and experimental studies have been done to analyze the anatomical and functional aspects of the internal auditory canal (IAC) in human beings since there are great inter-individual variability and structural variations that may occur regarding the other adjacent structures. Objectives: The purpose of this study was to characterize the morphology of the internal auditory canal (IAC) during development using high resolution computed tomography (CT) and to analyze its dimensions, which will be determined by measuring the nearby areas and structures using a system of digital image processing. Patients and Methods: CT images of the IAC of 110 normal subjects aged 1 to 92 years (mean age, 46.5 years) of both genders were reviewed to determine the shape, area, opening width (OW), longitudinal length (LL), vertical diameter (VD) and distance from the vestibular aqueduct. Results: The shapes observed in children and adults were funnel-shaped (74% and 58.3%, respectively), cylindrical (22% and 30.9%, respectively) and bud-shaped (4% and 10.8%, respectively). The measurements by CT in children were: area= 50.30 mm 2 , OW = 7.53 mm, length = 11.17 mm, VD = 4.82 mm and the distance between the IAC and the vestibular aqueduct (VA) = 12.63 mm. In adults, the measurements were: area = 44.64 mm 2 , OW = 7.10 mm, length = 9.84 mm, VD = 4.47 mm and the distance between IAC and VA = 11.17 mm. Conclusions: CT images showed that the IAC has different shapes and when the measurements obtained for children were compared with those of adults, the parameters that presented statistically significant differences in either gender were length and diameter.

Research paper thumbnail of The External Opening of the Cochlear Aqueduct in Infants and Adults

Oto-Rhino-Laryngologia Nova, 2001

The purpose of the present study is the description of the shape and area of the cochlear aqueduc... more The purpose of the present study is the description of the shape and area of the cochlear aqueduct (CA) opening by means of molds obtained from infant and adult temporal bones. Material and Methods: Through molding techniques the evaluation was performed in 118 temporal bones of infants (5-60 months) and of adults (19-89 years), dimensions and shapes being evaluated through computerized image processing. Results and Conclusions: The data shows that the area of the opening is significantly smaller in children than in adults (7.32 B 3.32 versus 18.48 B 6.42 mm 2 ). In infants, in 56% the shape of the opening was triangular; in adults triangularity was 100%. The variability in the shape and size of the CA opening in infants suggests adaptations of the CA opening during cranial growth.

Research paper thumbnail of The External Opening of the Cochlear Aqueduct in Infants and Adults

Oto-rhino-laryngologia Nova, 2001

The purpose of the present study is the description of the shape and area of the cochlear aqueduc... more The purpose of the present study is the description of the shape and area of the cochlear aqueduct (CA) opening by means of molds obtained from infant and adult temporal bones. Material and Methods: Through molding techniques the evaluation was performed in 118 temporal bones of infants (5-60 months) and of adults (19-89 years), dimensions and shapes being evaluated through computerized image processing. Results and Conclusions: The data shows that the area of the opening is significantly smaller in children than in adults (7.32 B 3.32 versus 18.48 B 6.42 mm 2 ). In infants, in 56% the shape of the opening was triangular; in adults triangularity was 100%. The variability in the shape and size of the CA opening in infants suggests adaptations of the CA opening during cranial growth.

Research paper thumbnail of Anatomical Variation of the Brachiocephalic Trunk and Common Carotid Artery in Neck Dissection

International Journal of Morphology, 2009

SUMMARY: Variations in the trajectory of the brachiocephalic trunk and the common carotid artery ... more SUMMARY: Variations in the trajectory of the brachiocephalic trunk and the common carotid artery predispose to disorders which might be critical in a tracheotomy and/or surgeries. Dissection of 110 formol fixed adult cadavers, both sexes, were performed to increase the anatomic ...

Research paper thumbnail of N-Carboxyalkyl derivatives of 3-hydroxy-4-pyridinones: synthesis, complexation with Fe(III), Al(III) and Ga(III) and in vivo evaluation

Journal of inorganic biochemistry, Jan 30, 2002

Research paper thumbnail of N-Arylamine derivatives of 3-hydroxy-4-pyridinones: solution studies and bioevaluation in view of Al-detoxification roles

Analytical and bioanalytical chemistry, 2005

A study of a series of bifunctional 3-hydroxy-4pyridinone derivatives, containing side-chains wit... more A study of a series of bifunctional 3-hydroxy-4pyridinone derivatives, containing side-chains with various alkyl-aryl-amine-amides as extra-functional groups, was conducted to assess the relevance of those groups to the Al-chelating affinity, the lipo-hydrophilic balance of the compounds, and 67 Ga biodistribution in mice, in view of their potential use as Al-decorporating agents; the results were compared with those for the drug Deferriprone. Their acid-base properties and Al-chelating affinity in aqueous solution were studied by potentiometric techniques. These ligands form very stable trischelated Al complexes and the non-chelating extragroups are only responsible for small differences in the complex stability (DpAl £ 1.2). At physiological pH the major ligand/complex species have different charges, because of the different extent of protonation of the ligands. The introduction of the different groups induces a well-balanced stepwise-like lipo-hydrophilic character (À0.2<log D oct./water <+1.1). The effect of each ligand on the biodistribution of 67 Ga in overloaded mice is rapid blood clearance for all of them, but with different biodistribution patterns, namely excretion pathways and brain uptake/clearance, thus suggesting potential different clinical use.

Research paper thumbnail of Effects of a uranium mine effluent in the early-life stages of Rana perezi Seoane

Science of The Total Environment, 2008

Amphibians have been reported as sensitive organisms whose survival has been impaired by several ... more Amphibians have been reported as sensitive organisms whose survival has been impaired by several environmental factors. Nevertheless, sometimes amphibians are found inhabiting extreme environments. Thus, in order to perceive how Iberian green frogs (Rana perezi Seoane) are able to survive in the ponds of a uranium mine (Central Portugal) this study aimed to assess the ecotoxicological effects promoted by the mine effluent in the early-life stages of this species. To attain this objective, eggs (collected in a nearby reference river) and laboratory hatching larvae were exposed during 96 h to different dilutions of the effluent. All the effects on the hatch success were recorded. The highest concentration of the effluent produced a significant decrease in body length of larvae, as well as a decrease in stimulus reactions and an increase in pigmentation along with tail deformities. A recovery assay showed an increased bioaccumulation of metals, uranium included, resulting from increased effluent exposure.

Research paper thumbnail of Iminodiacetyl-hydroxamate derivatives as metalloproteinase inhibitors: equilibrium complexation studies with Cu(II), Zn(II) and Ni(II)

Journal of Inorganic Biochemistry, 2003

Two new iminodiacetyl-hydroxamate derivatives, the N-benzyl-N-carboxymethyl-iminoacetohydroxamic ... more Two new iminodiacetyl-hydroxamate derivatives, the N-benzyl-N-carboxymethyl-iminoacetohydroxamic acid (H(2)L(1)) and the N-benzyl-N&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-hydroxypiperazine-2,6-dione (HL(2)), have been recently reported as very effective inhibitors against a set of zinc-containing matrix metalloproteinases (MMPs). Herein, aimed at understanding that inhibitory function, these compounds are studied in their complex formation equilibria with three biologically relevant first-row transition M(2+) metal ions (M=Cu, Zn, Ni) by using potentiometric and spectroscopic techniques. At physiological conditions, complexation of these metal ions by H(2)L(1) mostly occurs with formation of 1:1 species by tridentate co-ordination (O,N,N) (carboxylate-amino-hydroxamate), whereas complexation with HL(2) mainly involves the formation of 1:2 (M:L) species with normal (O,O) hydroxamate coordination. Moreover, at higher pH, H(2)L(1) is able to form a pentanuclear tetrameric copper complex with an interesting 12-metallacrown-4 structure.

Research paper thumbnail of Zinc(II) Complexation Behaviour of Sulfonamide-Based Enzyme Inhibitors

European Journal of Inorganic Chemistry, 2006

Sulfonamide derivatives containing extrafunctional groups, such as hydroxamic acids, hydroxypyrim... more Sulfonamide derivatives containing extrafunctional groups, such as hydroxamic acids, hydroxypyrimidinones and carboxylic acids, have been recently identified as inhibitors towards several zinc-containing enzymes, such as the matrix metalloproteinases (MMPs) and/or carbonic anhydrases (CAs). Since these inhibitors are supposed to bind the zinc ion at the active site, it was decided to study the zinc(II) complexation with a set of representative compounds in order to identify the most probable coordination modes and to find eventual relationships with the inhibitory properties. These studies were performed in aqueous solution, by potentiometry and 1H NMR spectroscopy, and in the solid phase, by infrared spectroscopy. The solution equilibrium studies indicate that these compounds present similar affinity for zinc (pZn ≈ 6). Under stoichiometric conditions, the formation of 1:1 metal complex species involves a preferential (O,O) coordination via the hydroxamic or hydroxypyrimidinone moieties, while the coordination via the sulfonamide groups could mainly be achieved under zinc excess conditions.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Research paper thumbnail of Protease Inhibitors: Synthesis of Bacterial Collagenase and Matrix Metalloproteinase Inhibitors Incorporating Succinyl Hydroxamate and Iminodiacetic Acid Hydroxamate Moieties

Journal of Enzyme Inhibition and Medicinal Chemistry, 2003

Novel matrix metalloproteinase (MMP)/bacterial collagenase inhibitors are reported, considering t... more Novel matrix metalloproteinase (MMP)/bacterial collagenase inhibitors are reported, considering the sulfonylated amino acid hydroxamates as lead molecules. A series of compounds was prepared by reaction of arylsulfonyl isocyanates with N-(5H-dibenzo[a,d]cyclohepten-5-yl)-and N-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yl) methyl glycocolate, respectively, followed by the conversion of the COOMe to the carboxylate/hydroxamate moieties. The corresponding derivatives with methylene and ethylene spacers between the polycyclic moiety and the amino acid functionality were also obtained by related synthetic strategies. These new compounds were assayed as inhibitors of MMP-1, MMP-2, MMP-8 and MMP-9, and of the collagenase isolated from Clostridium histolyticum (ChC). Some of the new derivatives reported here proved to be powerful inhibitors of the four MMPs mentioned above and of ChC, with activities in the low nanomolar range for some of the target enzymes, depending on the substitution pattern at the sulfonylureido moiety and on the length of the spacer through which the dibenzosuberenyl/suberyl group is connected with the rest of the molecule. Several of these inhibitors also showed selectivity for the deep pocket enzymes (MMP-2, MMP-8 and MMP-9) over the shallow pocket ones MMP-1 and ChC. #

Research paper thumbnail of Comparison of portuguese soils from different geographical regions using physicochemical, biological and biochemical parameters

Journal of Soils and Sediments, 2008

Background, Aim and Scope As a way of getting a comprehensive assessment of soil quality it is ne... more Background, Aim and Scope As a way of getting a comprehensive assessment of soil quality it is necessary to gather information on several appropriate soil parameters as well as also to perceive their spatial variation between geographic regions. The present work aimed to characterize and compare soil samples from different geographical regions and vegetation covers in the Portuguese territory through the use of physicochemical, biological and biochemical parameters. The study also intended to ascertain if those parameters are sensitive tools that consistently respond to geographical variations. Methodology Physical and chemical (soil organic matter contents, moisture, pH and conductivity), biological (macroarthropod es and diversity) and biochemical (potential nitrification, dehydrogenase and acid phosphatase activities) soil parameters were determined for three different regions of Portugal. Several sub-areas were chosen within each region, in order to include main vegetation patches. At each sampling sub-area, 5 traps were randomly set up for the collection of macroarthropods. For each sampling location, diversity descriptors of soil macrofauna were calculated: species richness, β diversity, the Shannon diversity (H′) and Pielou evenness (J′) indices. A principal component analysis (PCA) was used to plot the different sampling locations based on physical and chemical parameters; a canonical correspondence analysis (CCA) was performed to analyse the relationships between soil fauna and environmental variables (physicochemical parameters and enzyme activities) and a partial canonical correspondence analysis (pCCA), with vegetation patches as covariables, was carried out to perceive their contribution to the variation in macroarthropod distribution. Results Physical and chemical parameters discriminated soils from the different geographic regions in the PCA. Nevertheless, a CCA of environmental variables (physical and chemical properties, dehydrogenase activity, acid phosphatase activity and potential nitrification) and soil macroarthropod catches only discriminated continental soils (Arouca and S. Domingos Mine) from insular ones (Porto Santo Island). The former were correlated with high dehydrogenase activity (DHA) and potential nitrification values, while soils from the Porto Santo Island were particularly correlated with high pH values and low moisture percentages. However, in spite of the extreme conditions, Porto Santo sampling sub-areas presented a great diversity of macroarthropods, especially when compared to the S. Domingos Mine. The pCCA showed that the different vegetation patches only explained 15% of the variation in edaphic species distribution. Discussion Even though physical and chemical parameters were sufficient to discriminate the different geographical regions included in this study, biochemical and biological parameters grouped continental regions, discriminating them from the insular one. According to the CCA triplot, it was evident that the sampling sub-areas from the island were negatively correlated with soil moisture, suggesting that this was probably the main factor for the suppression of the microbial parameters in the island. On the other hand, the location of the S. Domingos mine area, in a metallogenetic province — the Iberian Pyrite Belt — may have contributed to the dominance of taxa more adapted to higher background levels of heavy metals. Conclusions In order to perceive geographical variation among different regions, more information is needed regarding different vegetation covers and the chemical composition of their corresponding litter, as well as about other soil chemical parameters. Recommendations and Perspectives The data gathered in this study will help to distinguish variation in soil biological and biochemical parameters induced by abiotic conditions from the one promoted by anthropogenic disturbances.

Research paper thumbnail of Design, synthesis and molecular modeling study of iminodiacetyl monohydroxamic acid derivatives as MMP inhibitors

Bioorganic & Medicinal Chemistry, 2006

As the matrix metalloproteinases (MMPs) can be massively up-regulated in degenerative tissues and... more As the matrix metalloproteinases (MMPs) can be massively up-regulated in degenerative tissues and degrade the extracellular matrix, these key enzymes are promising targets for the therapy of cancer and other degenerative diseases. Here, we are presenting a series of new non-peptidic hydroxamate-based matrix metalloproteinase inhibitors, MMPIs, incorporating the iminodiacetic (IDA) hydroxamic acid scaffold, as mimics of truncated peptidic MMPIs. A series of alkylaryl and sulfonylaryl groups, on the IDA basic scaffold, was investigated with the aim of improving potency and selectivity against MMPs involved in degenerative diseases. The sulfonamide based IDA derivatives studied (compounds B1–B3) showed to be potent (nM range) against deep S1′ pocket MMPs enzymes (i.e., MMP-2).We present the design, synthesis and docking studies on a series of new non-peptidic hydroxamate-based matrix metalloproteinase inhibitors, incorporating the iminodiacetic hydroxamic acid scaffolds.

Research paper thumbnail of Alkylaryl-amino derivatives of 3-hydroxy-4-pyridinones as aluminium chelating agents with potential clinical application

Journal of Inorganic Biochemistry, 2003

The neurotoxicity of aluminium is well established and so strategies for suitable aluminium chela... more The neurotoxicity of aluminium is well established and so strategies for suitable aluminium chelating therapies, aimed at the treatment and/or amelioration of some neurological disorders, are of current interest. The present work describes a set of new bifunctional compounds containing a 3-hydroxy-4-pyridinone (3,4-HP) unit, as the aluminium chelating moiety, which is extra-functionalised with different alkyl-arylamine molecular segments, to account for the improvement on the biodistribution specificity of the chelating agents or the corresponding complexes. Besides the synthetic scheme, studies are performed to assess the properties of these compounds, namely in terms of lipophilicity, Al-chelating ability, speciation and in vivo 67Ga biodistribution. These studies show that the extrafunctional groups fortunately have small effects on the high Al chelating affinity of the 3,4-HP units, over a wide range of pH, but they lead to favourable changes on the lipo-hydrophilic balance of the ligands and on the complex speciation. Differences found in the biodistribution, namely the decrease of the blood-clearance rate and increase of the bone retention or the hepatobiliary excretion, seem to be mostly rationalized in terms of the increasing lipophilic character of the ligands.

Research paper thumbnail of N-Carboxyalkyl derivatives of 3-hydroxy-4-pyridinones: synthesis, complexation with Fe(III), Al(III) and Ga(III) and in vivo evaluation

Journal of Inorganic Biochemistry, 2002