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Biomedical subjects

J Pires

Publications and source records attributed to J Pires.

14 recordsLinked to original sources
PubMed2005

Prevalence of pulmonary tuberculosis and comparative evaluation of screening strategies in a Brazilian prison.

SETTING: A prison (1171 male inmates) in Rio de Janeiro, Brazil. OBJECTIVES: To determine the prevalence of active pulmonary tuberculosis (TB) and to assess the performance of several screening strategies. DESIGN: In a cross-sectional study, all inmates underwent chest radiographic screening. Subjects with abnormal findings underwent sputum smear examination and sputum culture. Taking this strategy as the reference, we assessed three targeted screening strategies to identify TB suspects: Strategy 1: cough >3 weeks; Strategy 2: WHO score > or = 5; Strategy 3: presence of at least one potentially TB-related symptom. RESULTS: The prevalence of TB cases was 4.6% (48/1052) and 2.7% for definite TB cases. If TB suspects identified by targeted screening had sputum smear examination alone, 37 (86.0%) of the 43 cases would have been missed by Strategy 1, 34/43 (79.1%) by Strategy 2 and 34/43 (79.1%) by Strategy 3. If TB suspects had both sputum smear examination and, for smear-negative subjects, chest radiography, respectively 28/43 (65.1%), 18/43 (41.9%) and 13/43 (30.2%) of cases would have been missed. CONCLUSION: All three targeted screening strategies were unreliable. Given the importance of early TB diagnosis in overcrowded and highly endemic settings, routine radiography-based screening may be warranted.

Adult↗
PubMed2003

Endoscopic obliteration of a recurrent tracheoesophageal fistula with enbucrilate and polidocanol in a child.

We present a difficult case of a recurrent tracheoesophageal fistula following primary surgical repair of esophageal atresia. After four unsuccessful attempts to close the fistula, which included three thoracotomies and one endoscopic obliteration using fibrin glue, successful recurrent tracheoesophageal fistula closure was attained with the endoscopic application of enbucrilate (Histoacrylate) combined with polidocanol. Enbucrilate was applied into the lumen of the fistula by bronchoscopy, and polidocanol (Sclerovein) was injected into the esophageal submucosa around the fistula by esophagoscopy. Three years after this treatment, the fistula remains apparently closed.

Bronchoscopy↗
PubMed2003

Downregulation of TNF-alpha and VEGF expression by Sp1 decoy oligodeoxynucleotides in mouse melanoma tumor.

Melanoma tumor growth and progression are highly dependent on adequate blood supply through angiogenesis. Since several genes involved in angiogenesis revealed potential binding sites for the transcription factor Sp1, we have examined the effects of local inoculation of Sp1 decoy oligodeoxynucleotides (ODNs) on the growth of transplanted murine melanoma tumors and the expression of VEGF and TNF-alpha within these tumors. Treatment with Sp1 decoy ODNs, but not their mutated form, led to a significant increase (P=0.041) of the tumor necrotic area, as evaluated morphometrically. Tumor necrosis was associated with a significant decrease of microvascular density (P=0.012) and relative vascular area (P=0.026), as determined by counting CD34-positive vascular structures within the tumor microenvironment of Sp1 decoy ODNs and control ODN-treated tumors. RT-PCR experiments showed a strong decrease in the levels of VEGF188 and VEGF164 isoforms and a moderate decrease of TNF-alpha in Sp1 decoy-treated tumors. Taken together, our results indicate that Sp1 decoy ODNs may inhibit angiogenesis by affecting the gene expression of key players in angiogenesis such as TNF-alpha and VEGF. These findings indicate that Sp1 decoy ODNs may be a potential new therapeutic tool in antiangiogenic therapy.

Animals↗
PubMed2000

Treatment of experimental allergic encephalomyelitis (EAE) induced by guinea pig myelin basic protein epitope 72-85 with a human MBP(87-99) analogue and effects of cyclic peptides.

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory and demyelinating disease of the central nervous system and is an animal model of multiple sclerosis (MS). In the present report, a linear analogue and a series of cyclic semi-mimetic peptides were designed and synthesized based on the human myelin basic protein (MBP(87-99)) epitope (Val87-His-Phe-Phe-Lys-Asn-Ile-Val-Thr-Pro-Arg-Thr-Pro90) and on Copolymer I (a mixture of random polymers of Ala, Gln, Lys and Tyr used to treat MS). These analogues were designed looking for suppressors of EAE induced by guinea pig MBP(72-85) epitope (Gln-Lys-Ser-Gln-Arg-Ser-Gln-Asp-Glu-Asn-Pro-Val) in Lewis rats. The linear analogue [Arg91,Ala96]MBP(87-99), in which Arg substitutes Lys91 and Ala substitutes Pro96, was found to be a strong inhibitor which when administered to Lewis rats together with the encephalitogenic agonist MBP(72-85) completely prevented the induction of EAE. In contrast, three N- and C-termini amide-linked cyclic semi-mimetic peptides, [cyclo-Phe-Arg-Asn-Ile-Val-Thr-Ala-Acp (1), cyclo-Phe-Ala-Arg-Gln-Acp (2), cyclo-Tyr-Ala-Lys-Gln-Acp (3)] as well as a Lys side chain and C-terminous cyclic semi mimetic peptide cyclo(Lys, Acp)-Phe-Lys-Asn-Ile-Val-Thr-Ala-Acp (4) which contain segments of MBP(87-99) or are constituted from immunophoric residues of copolymer 1, were ineffective in inducing or inhibiting EAE in Lewis rats. However co-injection of cyclic analogues with MBP(72-85) delayed the onset of EAE indicating a modulatory effect on the EAE activity of MBP(72-85). These findings suggest that molecule length, size of cyclic moiety and backbone conformation are important elements for immunogenic activity. Moreover blockade of MBP(72-85) induced EAE by the unrelated peptide [Arg91,Ala56]MBP(87-99) could indicate that the mechanism of inhibition is not due to binding competition but rather due to the delivery of a negative signal by the antagonist which overcomes the agonist response possibly through the activation of antigen specific regulatory T cells.

Animals↗
PubMed1999

An improved synthesis of an umbelliferyl 5-thioxylopyranoside, precursor of the antithrombotic drug Iliparcil.

4-Ethyl-2-oxo-2H-1-benzopyran-7-yl 2,3,4-tri-O-acetyl-5-thio-beta-D-xylopyranoside, a synthetic intermediate of the orally active antithrombotic compound Iliparcil, has been prepared in 44-47% isolated yield. Different conditions were used for the glycosylation of 4-ethyl-2H-7-hydroxy-1-benzopyran-2-one 6 applying 2,3,4-tri-O-acetyl-5-thio-D-xylopyranosyl bromide (2), the analogous beta-chloride 3 or the alpha-trichloroacetimidate 5 as donors. With halides 2 and 3, the reaction was carried out in the presence of ZnO-ZnCl2 or ZnO alone. Both promoters are cheap, safe and therefore compatible with large-scale industrial processes.

Benzopyrans↗
PubMed1990

[Indirect articular lymphography using Tc 99m-labeled Dextran in animals].

Looking for a standardization of the articular lymphoscintigraphy, an experimental research was conducted on 14 dogs injected in the ankle, with 2.5 mCi of 99m Tc-labeled dextran (P.M. = 70,000). Good scintigraphic images of the lymphatic system have been obtained. After having collected blood samples during the experimentation as well as aliquots of organs and of tissues, after the necropsy of the animal, it was verified that the 99m Tc-labeled dextran was useful for quantitative studies of the articular lymphatic drainage. The activities attained, in the drainage lymph nodes of injected articulation, are 152 times superior to those obtained in the kidney and one gramma of popliteal ganglion was 8929 times more active than one gramma of blood. The dextran 70,000, widely used in our clinical routine, can be injected to the human being, without any risk, and it may be the tracer which permits studies of the articular lymphatic drainage and the usage of the lymphoscintigraphy, already in expansion in many other Medicine branches, in the articular studies, nowadays.

Animals↗
PubMedDate not supplied

Discovery and design of novel inhibitors of botulinus neurotoxin A: targeted 'hinge' peptide libraries.

Intoxication by the zinc protease botulinus neurotoxin A (BoNT-A) results from cleavage of a single Q-R bond in the neuronal protein SNAP-25, which disables the docking mechanism required for neurotransmitter release. In the present study, potential inhibitors of BoNT-A were assessed from their effects on the BoNT-A cleavage of a synthetic 17-mer peptide (SNAP-25, residues 187-203) spanning the Q-R cleavage site. Compounds that inhibited BoNT-A included thiols (zinc chelators) such as dithiothreitol, dimercaptopropanesulfonic acid, mercaptosuccinic acid and captopril. In addition, compounds containing multiple acidic functions, such as the SNARE motif V2 (ELDDRADALQ), the tripeptide Glu-Glu-Glu and the steroid glycoside glycyrrhizic acid, were effective inhibitors. 'Hinge' peptide mini-libraries (PMLs) having the structure acetyl-X(1)-X(2)-linker-X(3)-X(4)-NH(2) or X(1)-X(2)-linker-X(3), where X(1)-X(4) were mixtures of selected amino acids and the flexible linker was 4-aminobutyric acid, also provided effective inhibition. Targeted PMLs containing the acidic amino acids Asp and Glu, the scissile-bond amino acids Gln and Arg and the zinc chelators His and Cys produced pronounced inhibition of BoNT-A. Deconvolution of these libraries will provide novel ligands with improved inhibitory potency as leads in the design of peptide mimetics to treat BoNT poisoning.

Antitoxins↗
PubMedDate not supplied

Evaluation of gaseous hydrogen fluoride as a convenient reagent for parallel cleavage from the solid support.

We have tested the limits of gaseous hydrogen fluoride as an agent for parallel detachment of organic molecules from the solid support. Peptides were chosen as relatively sensitive models for this reaction. Acid-catalyzed amide bond hydrolysis, side chain modification (tryptophan and other unnatural amino acids) by the protecting group residues as well as dehydration of serine and asparagine was followed. The technique of cleavage of side chain protection prior to the resin cleavage has given satisfactory results. Two-step deprotection and cleavage from benzhydrylamine resin by TFA and HF was compared to the deprotection and cleavage by TFA from Knorr resin.

Amino Acid Sequence↗
PubMedDate not supplied

[Foreign bodies in the tracheobronchial tree. 12 years' experience].

During a period of twelve years--January 1983 to December 1994, 371 children suspected of foreign body inhalation were admitted in Hospital Pediatric of Coimbra. The diagnosis was confirmed in 200 of them (54%), and this group was analysed. The incidence has increased until 1989 and stabilized in the last 5 years with a median of 18 cases/year. Two third of the children were boys and 84% were under three years old. A history of choking was obtained in 87% of the patients but only 39% of the cases had an early diagnosis (within 24 hours). The most frequent clinical findings were abnormal auscultation, sternal retraction, cough, wheezing and fever. Sixty percent of them were asymptomatic. The chest radiology findings were air trapping in 45%, consolidation in 21% and in 17% there were no abnormalities. Radiopaque foreign bodies were found in 9%. Organic bodies were the most frequent (74%) and among these, peanuts, lupines and beans. Food aspiration in one case took to cardiorespiratory arrest and in another with a late diagnosis bronchial stenosis needed a surgical treatment. Complications of foreign bodies extraction had no consequences.

Adolescent↗