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Acesso aberto (Open Access)
1,4-Diamino-2-butanone, a putrescine analogue, promotes redox imbalance in Trypanosoma cruzi and mammalian cells
(Elsevier B.V., 2012-12-15) Soares, Chrislaine O; Colli, Walter; Bechara, Etelvino José Henriques [UNIFESP]; Alves, Maria Julia Manso; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
The putrescine analogue 1,4-diamino-2-butanone (DAB) is highly toxic to various microorganisms, including Trypanosoma cruzi. Similar to other a-aminocarbonyl metabolites. DAB exhibits pro-oxidant properties. DAB undergoes metal-catalyzed oxidation yielding H2O2, NH4+ ion, and a highly toxic alpha-oxoaldehyde. in vitro. DAB decreases mammalian cell viability associated with changes in redox balance. Here, we aim to clarify the DAB pro-oxidant effects on trypomastigotes and on intracellular T. cruzi amastigotes. DAB (0.05-5 mM) exposure in trypomastigotes, the infective stage of T. cruzi, leads to a decline in parasite viability (IC50 c.a. 0.2 mM DAB; 4 h incubation), changes in morphology, thiol redox imbalance, and increased TcSOD activity. Medium supplementation with catalase (2.5 mu M) protects trypomastigotes against DAB toxicity, while host cell invasion by trypomastigotes is hampered by DAB. Additionally, intracellular amastigotes are susceptible to DAB toxicity. Furthermore, pre-treatment with 100-500 mu M buthionine sulfoximine (BSO) of LLC-MK2 potentiates DAB cytotoxicity, whereas 5 mM N-acetyl-cysteine (NAC) protects cells from oxidative stress. Together, these data support the hypothesis that redox imbalance contributes to DAB cytotoxicity in both T. cruzi and mammalian host cells. (C) 2012 Elsevier Inc. All rights reserved.
Acesso aberto (Open Access)
1-[(Z)-1-Bromo-2-(butyldichloro-lambda(4)tellanyl)ethenyl]cyclohex-1-ene
(Wiley-Blackwell, 2011-07-01) Zukerman-Schpector, Julio; Caracelli, Ignez; Guadagnin, Rafael Carlos [UNIFESP]; Stefani, Helio A.; Tiekink, Edward R. T.; Universidade Federal de São Carlos (UFSCar); Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); Univ Malaya
The Te-IV atom in the title compound, [Te(C4H9)(C8H10Br)Cl-2] or C12H19BrCl2Te, is in a distorted psi-trigonal-bipyramidal geometry, with the lone pair of electrons projected to occupy a position in the equatorial plane, and with the Cl atoms being mutually trans [172.48 (4)degrees]. Close intramolecular [Te center dot center dot center dot Br = 3.3444 (18) angstrom] and intermolecular [Te center dot center dot center dot Cl = 3.675 (3) angstrom] interactions are observed. the latter lead to centrosymmetric dimers which assemble into layers in the bc plane. the primary connections between layers are of the type C-H center dot center dot center dot Cl.
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1.70 angstrom X-ray structure of human apo kallikrein 1: Structural changes upon peptide inhibitor/substrate binding
(Wiley-Blackwell, 2005-03-01) Laxmikanthan, G.; Blaber, S. I.; Bernett, M. J.; Scarisbrick, I. A.; Juliano, M. A.; Blaber, M.; Florida State Univ; Mayo Clin & Mayo Grad Sch Med; Universidade Federal de São Paulo (UNIFESP)
Human kallikreins are serine proteases that comprise a recently identified large and closely related 15-member family. the kallikreins include both regulatory- and degradative-type proteases, impacting a variety of physiological processes including regulation of blood pressure, neuronal health, and the inflammatory response. While the function of the majority of the kallikreins remains to be elucidated, two members are useful biomarkers for prostate cancer and several others are potentially useful biomarkers for breast cancer, Alzheimer's, and Parkinson's disease. Human tissue kallikrein (human K1) is the best functionally characterized member of this family, and is known to play an important role in blood pressure regulation. As part of this function, human K1 exhibits unique dual-substrate specificity in hydrolyzing low molecular weight kininogen between both Arg-Ser and Met-Lys sequences. We report the X-ray crystal structure of mature, active recombinant human apo K1 at 1.70 Angstrom resolution. the active site exhibits structural features intermediate between that of apo and pro forms of known kallikrein structures. the S2 to S2' pockets demonstrate a variety of conformational changes in comparison to the porcine homolog of K1 in complex with peptide inhibitors, including the displacement of an extensive solvent network. These results indicate that the binding of a peptide substrate contributes to a structural rearrangement of the active-site Ser 195 resulting in a catalytically competent juxtaposition with the active-site His 57. the solvent networks within the S1 and S1' pockets suggest how the Arg-Ser and Met-Lys dual substrate specificity of human K1 is accommodated. Proteins (C) 2005 Wiley-Liss, Inc.
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A 12-wk follow-up study to evaluate the effects of mixing insulin lispro and insulin glargine in young individuals with type 1 diabetes
(Wiley-Blackwell, 2012-11-01) Lucchesi, Maria B. B. [UNIFESP]; Komatsu, William R. [UNIFESP]; Gabbay, Monica Andrade Lima [UNIFESP]; Dib, Sergio A. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Objective: This study was performed to compare in real-life conditions the serum profile of insulin lispro (IL) after a subcutaneous (SC) injection, separate and mixed with insulin glargine (IG), using a sensitive radioimmunoassay for the specific determination of serum IL, and to evaluate the 12-wk effect of the mixture on glycemic control in young individuals with type 1 diabetes.Research design and methods: the IL serum profiles were evaluated in 10 individuals with type 1 diabetes [age 21.9 +/- 3.8 yr; diabetes duration 13.4 +/- 4.9 yr; body mass index 25.1 +/- 3.2 kg/m(2); hemoglobin A1c (HbA1c) 8.3 +/- 0.8%] during a mixed meal test (MMT) using IL and IG as separate (baseline) and mixed injection. the glycemic variability by continuous glucose monitoring system (CGMS) and the long-term diabetes control with HbA1c were also evaluated at baseline and after 12 wk mixing the two insulins.Results: the mixture of IL with IG decreased IL maximum serum concentration (C-maxIL) (29.4 +/- 5.1 mu U/mL vs. 13.7 +/- 4.2 mu U/mL; p = 0.03) without changing the time to reach the Cmax (T-maxIL), the IL area under the curve (AUC(IL0-240)), and the glucose dynamics during the MMT. the glucose variability and the HbA1c were equivalent to baseline after 12 wk mixing both insulins.Conclusions: These data suggest that mixing IL with IG immediately before the SC injection decreases IL serum peak concentration without affecting the glycemic profile after 12 wk in this group with type 1 diabetes mellitus.
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17-hydroxylase/C17,20-lyase (CYP17) is not the enzyme responsible for side-chain cleavage of cortisol and its metabolites
(Elsevier B.V., 2008-07-01) Shackleton, Cedric H. L.; Neres, Marcos S. [UNIFESP]; Hughes, Beuerly A.; Stewart, Paul M.; Kater, Claudio E. [UNIFESP]; Univ Birmingham; Universidade Federal de São Paulo (UNIFESP)
The question addressed in this study was the nature of the enzyme required to remove the side-chain of 17-hydroxycorticosteroids, leading in the case of cortisol to the excretion of 11 beta-hydroxyandrosterone, 11-oxo-androsterone and the corresponding etiocholanolones. We questioned whether it could be CYP17, the 17-hydroxylase/17,20-lyase utilized in androgen synthesis. the conversion of exogenous cortisol to C-19 steroids in patients with complete 17-hydroxylase deficiency (17HD) was studied rationalizing that if CYP17 was involved no C-19 steroids would be formed. the urinary excretion of the four 11-oxy-C-19 steroids as well as many of the major C-21 cortisol metabolites were measured by GC/MS. Our results showed that the conversion of cortisol to C-19 steroids was normal in 17HD indicating that a currently unidentified enzyme must be responsible for this transformation.A secondary goal was to determine to what extent 11-oxy-C-19 steroids were metabolites of cortisol or adrenal synthesized 11 beta-hydroxyandrostenedione. Since cortisol-treated 17HD patients cannot produce androstenedione, all C-19 11-oxy-metabolites excreted must be derived from exogenous cortisol. the extent to which 17HD patients have lower relative excretion of C-19 steroids should reflect the absence of lip-hydroxyandrostenedione metabolites. Our results showed almost all of 11-oxo-etiocholanolone and 11 beta-hydroxyetiocholanolone were cortisol metabolites, but in contrast the excretion of lip-hydroxyandrosterone was less than 10% that of normal individuals, indicating that in excess of 90% must be a metabolite of 11 beta-hydroxyandrostenedione. (C) 2008 Elsevier Inc. All rights reserved.
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17p duplicated Charcot-Marie-Tooth 1A - Characteristics of a new population
(Dr Dietrich Steinkopff Verlag, 2005-08-01) Marques, W.; Freitas, M. R.; Nascimento, OJM; Oliveira, A. B.; Calia, L.; Melo, A.; Lucena, R.; Rocha, V; Barreira, A. A.; Universidade de São Paulo (USP); Universidade Federal Fluminense (UFF); Universidade Federal de São Paulo (UNIFESP); Universidade Federal da Bahia (UFBA)
The most frequent type of Charcot-Marie-Tooth (CMT) neuropathy is that associated with the 17p11.2-p12 chromosome duplication, whose characteristics have been well described in European and North American populations. in this study, we analyzed a Brazilian population exhibiting the mutation, found in 57 patients from 42 families (79%) of a cohort of 53 families with demyelinating CMT. Almost 20% of the duplicated cases were sporadic. in 77% of the duplicated families the mutation event occurred in the hot spot area of the CMT1A-Rep region. Forty-five percent of patients were females, 84% were Caucasians and 13% of African descent. Distal limb weakness was the most frequent abnormality, appearing in 84% of patients, although uncommon manifestations such as severe proximal weakness, floppy baby syndrome, diaphragmatic weakness and severe scoliosis were also observed. One patient was wheelchair-bound, and three suffered severe hand weakness. Sensory abnormalities were detected in 84% of the cases, but 80% were unaware of this impairment. Twelve patients complained of positive sensory manifestations such as pain and paresthesias. Progression was reported by 40%. Motor conduction velocities in the upper limbs were always less than 35 m/s, and less than 30.4 m/s in the peroneal nerve. the findings of this study expand the clinical spectrum of the disease.
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An 18-Week, Prospective, Randomized, Double-Blind, Multicenter Study of Amlodipine/Ramipril Combination Versus Amlodipine Monotherapy in the Treatment of Hypertension: the Assessment of Combination Therapy of Amlodipine/Ramipril (ATAR) Study
(Elsevier B.V., 2008-09-01) Miranda, Roberto Dischinger [UNIFESP]; Mion, Decio; Rocha, Joao Carlos; Kohlmann, Oswaldo [UNIFESP]; Mota Gomes, Marco Antonio; Kerr Saraiva, Jose Francisco; Amodeo, Celso; Luna Filho, Braulio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); Universidade Estadual de Campinas (UNICAMP); Hlth Sci Univ Alagoas; Catholic Univ; Dante Pazzanese Cardiol Inst
Background: A combination of antihypertensive agents of different drug classes in a fixed-dose combination (FDC) may offer advantages in terms of efficacy, tolerability, and treatment compliance. Combination of a calcium channel blocker with an angiotensin-converting enzyme inhibitor may act synergistically to reduce blood pressure (BP).Objective: the aim of this study was to compare the efficacy and tolerability of an amlodipine/ramipril FDC with those of amlodipine monotherapy.Methods: This 18-week, prospective, randomized, double-blind study was conducted at 8 centers across Brazil. Patients with stage 1 or 2 essential hypertension were enrolled. After a 2-week placebo run-in phase, patients received amlodipine/ramipril 2.5/2.5 mg or amlodipine 2.5 mg, after which the doses were titrated, based on BP, to 515 then 10/10 mg (amlodipme/ramipril) and 5 then 10 mg (amiodipine). the primary end point was BP measured in the intent-to-treat (ITT) population. Hematology and serum biochemistry were assessed at baseline and study end. Tolerability was assessed using patient interview, laboratory analysis, and physical examination, including measurement of ankle circumference to assess peripheral edema.Results: A total of 222 patients completed the study (age range, 40-79 years; FDC group, 117 patients [mean dose, 7.60/7.60 mg]; monotherapy, 105 patients [mean dose, 7.97 mg]). the mean (SD) changes in systolic BP (SBP) and diastolic BP (DBP), as measured using 24-hour ambulatory blood pressure monitoring (ABPM) and in the physician's office, were significantly greater with combination therapy than monotherapy, with the exception of office DBP (ABPM, -20.76 [1.25] vs -15.80 [1.18] mm Hg and -11.71 [0.78] vs -8.61 [0.74] mm Hg, respectively [both, P = 0.004]; office, -27.51 [1.40] vs -22.84 [1.33] min Hg [P = 0.012] and -16.41 [0.79] vs -14.64 [0.75] mm Hg [P = NS], respectively). in the ITT analysis, the mean changes in ambulatory, but not office-based, BP were statistically significant (ABPM: SBP, -20.21 [1.14] vs -15.31 [1.12] mm Hg and DBP, -11.61 [0.72] vs -8.42 [0.70] mm Hg, respectively [both, P = 0.002]; office: SBP, -26.60 [1.34] vs -22.97 [1.30] mm Hg and DBP, -16.48 [0.78] vs -14.48 [0.75] mm Hg [both, P = NS]). Twenty-nine patients (22.1%) treated with combination therapy and 41 patients (30.6%) treated with monotherapy experienced >= 1 adverse event considered possibly related to study drug. the combmation-therapy group had lower prevalence of edema (7.6% vs 18.7%; P = 0.011) and a similar prevalence of dry cough (3.8% vs 0.8%; P = NS). No clinically significant changes in laboratory values were found in either group.Conclusions: in this population of patients with essential hypertension, the amlodipine/ramipril FDC was associated with significantly reduced ambulatory and office-measured BP compared with amlodipine monotherapy, with the exception of office DBP. Both treatments were well tolerated. (Clin Ther. 2008;30: 1618-1628) (C) 2008 Excerpta Medica Inc.
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2 RECEPTOR SUBTYPES ARE INVOLVED in the CONTRACTILE COMPONENT of the GUINEA-PIG ILEUM RESPONSES TO ENDOTHELINS
(Lippincott-raven Publ, 1993-01-01) Miasiro, N. [UNIFESP]; Paiva, ACM [UNIFESP]; Ihara, M.; Yano, M.; BANYU PHARMACEUT CO LTD; Universidade Federal de São Paulo (UNIFESP)
Endothelin-I (ET-1) and endothelin-3 (ET-3) induced a biphasic response (relaxation and contraction) in the guinea pig ileum. Short-term activation of protein kinase C (PKC) with phorbol 12,13-dibutyrate (PDBu) inhibited the contractile but not the relaxing component of the responses, as did H-7. Long-term pretreatment with PDBu reversed the short-term inhibition but did not affect the tachyphylaxis induced by ET-1. These results suggest that PKC contributes to ET-1 contraction but not to tachyphylaxis. the ETA antagonist BQ- 123, at 34 nM, competitively inhibited ET-1 contraction, but at 340 nM the inhibition was noncompetitive. Dose-response curves for ET-1 relaxation were shifted to the left. for ET-3, BQ-123 (340 nM) only decreased the maximal contractile response of the dose-response curve without affecting the relaxation. We suggest that in this tissue there is one receptor for ET-1-induced contraction, which is competitively antagonized by BQ-123, and another one for ET-3-induced contraction, which is noncompetitively antagonized by BQ-123.
Acesso aberto (Open Access)
2-chlorovinyl tellurium dihalides, (p-tol)Te[C(H)=C(Cl)Ph]X2 for X = Cl, Br and I: variable coordination environments, supramolecular structures and docking studies in cathepsin B
(Sociedade Brasileira de Química, 2010-01-01) Caracelli, Ignez; Zukerman-Schpector, Julio; Maganhi, Stella H; Stefani, Hélio A; Guadagnin, Rafael Carlos [UNIFESP]; Tiekink, Edward R. T; Universidade Federal de São Carlos Departamento de Física; Universidade Federal de São Carlos Departamento de Química Laboratório de Cristalografia, Estereodinâmica e Modelagem Molecular; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP); University of Malaya Department of Chemistry
Crystallography shows that the Te atom in each of (p-tol)Te[C(H)=C(Cl)Ph]X2, for X = Cl (1), Br (2) and I (3), is within a distorted Ψ-pentagonal bipyramidal geometry. An E configuration for the vinyl group in (1) precludes the formation of an intramolecular Te···Cl interaction so that an intramolecular Te···π interaction is found instead. The coordination environment features a linear Cl-Te-Cl arrangement with the pentagonal plane defined by the two C atoms of the organic substituents, an intermolecular Te···Cl contact, a Te···π interaction and a stereochemically active lone pair of electrons. In the X = Br (2) and I (3) structures, similar coordination geometries are found but the Te···π contact is replaced by an intramolecular Te···Cl contact owing to the adoption of a Z configuration about the vinyl bond. The differences in structure are readily explained in terms of electronic effects. Docking studies of cathepsin B with (1')-(3'), i.e. 1-3 less one Te-bound halide, show efficient binding through the agency of covalent Te-S Cys29 bonds with stabilization afforded by a combination of N-H···π, C-H···π and Cl vinyl···H interactions. These results comparable favorably with known inhibitors of cathepsin B suggesting the title compounds have potential biological activity.
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25-Hydroxyvitamin D level does not reflect intestinal calcium absorption: an assay using strontium as a surrogate marker
(Springer, 2015-05-01) Rodrigues Camargo, Marilia Brasilio [UNIFESP]; Vilaca, Tatiane [UNIFESP]; Hayashi, Lilian Fukusima [UNIFESP]; Ferreira Rocha, Olguita G.; Lazaretti-Castro, Marise [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Technol Ctr Minas Gerais CETEC
There is conflicting evidence as to the optimal serum 25-hydroxyvitamin D [25(OH)D] concentration for intestinal calcium absorption (Abs-Ca). Our purpose was to assess the relationship between vitamin D status and Abs-Ca in postmenopausal women. Fifty volunteers with low bone mass were grouped according to their serum 25(OH)D concentration as follows: mild deficient, < 50 nmol/L (DEF) and sufficient, a parts per thousand yen75 nmol/L (SUF). the subjects were submitted to an oral strontium overload test to assess their Abs-Ca. Fasting blood samples were obtained to perform the relevant hormonal and biochemical tests. After the subjects received the test solution, blood samples were drawn at 30, 60, 120, and 240 min to determine the strontium concentrations. Abs-Ca was indirectly expressed as the area under the serum strontium concentration curve (AUC). A repeated measures ANOVA was performed to determine the differences among the groups. Pearson's correlation and multiple linear regression analysis were used to study the associations between the variables. the mean 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] concentrations differed between the groups (SUF vs. DEF) as follows: 98.7 +/- A 18.2 vs. 38.4 +/- A 8.5 nmol/L (p < 0.001) and 36.2 +/- A 10.2 vs. 24.9 +/- A 4.6 pg/mL (p < 0.001), respectively. There was no statistically significant difference between the groups for parathyroid hormone and AUC. Only 1,25(OH)(2)D influenced the strontium absorption in the last 2 h of the test. in the studied population, no correlation between levels of 25(OH)D and Abs-Ca was found. Only 1,25(OH)(2)D influenced Abs-Ca as measured by a strontium absorption test.
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THE 35/50 KDA SURFACE-ANTIGEN of TRYPANOSOMA-CRUZI METACYCLIC TRYPOMASTIGOTES, AN ADHESION MOLECULE INVOLVED in HOST-CELL INVASION
(Blackwell Science Ltd, 1993-02-01) Ruiz, R. D.; Rigoni, V. L.; Gonzalez, J.; Yoshida, N.; Universidade Federal de São Paulo (UNIFESP)
We have previously shown that monoclonal antibodies directed to the 90 kDa glycoprotein and the 35150 kDa glycoconjugate, present on the surface of Trypansoma cruzi metacyclic trypomastigotes, inhibited host cell invasion. Here we investigated whether these molecules could be the ligands for the target cell receptor. Binding assays were performed by incubating Vero cells with sonicated parasite extract. Detection of bound parasite components was carried out by using monoclonal antibodies (MoAbs) 1G7 and 10D8, which recognize the 90 kDa and the 35/50 kDa antigens respectively. These experiments revealed that the 35/50 kDa glycoconjugate of metacyclic forms, but not the 1G7-reactive antigen, binds to Vero cells. the purified 35/50 kDa antigen bound to Vero cells and inhibited the entry of metacyclic forms in a dose-dependent manner. Although to a lesser extent, an immunologically related 35/50 kDa antigen of non-infective epimastigotes also bound to Vero cells but it was unable to inhibit parasite penetration at a concentration (100 mug/ml) in which metacyclic antigen exhibited more than 60% inhibition. All these data suggest that the metacyclic 35/50 kDa surface glycoconjugate is a ligand to the host cell in the process of T. cruzi invasion.
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A 36-residue peptide contains all of the information required for 7B2-mediated activation of prohormone convertase 2
(Amer Soc Biochemistry Molecular Biology Inc, 1999-07-23) Muller, L.; Zhu, P. M.; Juliano, Maria Aparecida [UNIFESP]; Juliano, Luiz [UNIFESP]; Lindberg, I; Louisiana State Univ; Universidade Federal de São Paulo (UNIFESP)
The prohormone convertases (PCs) are serine proteinases responsible for the processing of secretory protein precursors. PC2 is the only member of this family whose activation requires intracellular interaction with a helper protein, the neuroendocrine protein 7B2, in order to gain a better understanding of the mechanism of proPC2 activation, we have characterized the structural determinants of 7B2 required for proPC2 activation. We had already identified a proline-rich binding determinant in the 21-kDa domain, the portion of 7B2 responsible for proPC2 activation. We have now investigated the function of the weakly conserved amino-terminal portion of 21-kDa 7B2 by sequential deletions. Mutant proteins were analyzed in four assays: binding to proPC2, facilitation of proPC2 maturation, and activation of proPC2 in vivo and in vitro. We found that the aminoterminal half of 7B2 is not involved in proPC2 activation, and we identified an active 36-residue peptide that contains the previously characterized proline-rich sequence as well as an alpha-helix and the only disulfide bond of 7B2. Mutation of the cu-helix and of the cysteines demonstrated that these determinants are absolutely required for PC2 activation, Thus, the 186-residue full-length 7B2 rat protein can be functionally reduced to an internal segment of only 36 residues.
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3q27 Aberrations in a Childhood Ovary Teratoma With Associated Malignant Germ Cell Component
(Wiley-Blackwell, 2009-03-01) Brassesco, Maria Sol; Castro-Gamero, Angel Mauricio; Valera, Elvis Terci; Neder, Luciano; Elias, Jorge; Tone, Luiz Gonzaga; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
Cytogenetic Studies of childhood ovary tumors have been poorly described. in the present article, the cytogenetic findings of an ovarian teratoma with malignant germ cell (yolk-sac) component occurring in an 8-year-old female are detailed. GTG-banding showed a karyotype of 46,XX, t(3;20)(q27;q13.3) [4]/46,XX, del3q27 [3]/46,XX [30]. Previous Studies have demonstrated common sites of loss of heterozygosity at 3q27-q28 region in different types of cancer, suggesting the presence of tumor Suppressor genes within this region. Pediatr Blood Cancer 2009;52:398-401. (C) 2008 Wiley-Liss, Inc.
Acesso aberto (Open Access)
3º Consenso Brasileiro para pesquisa de autoanticorpos em células HEp-2 (FAN): recomendações para padronização do ensaio de pesquisa de autoanticorpos em células HEp-2, controle de qualidade e associações clínicas
(Sociedade Brasileira de Reumatologia, 2009-04-01) Dellavance, Alessandra [UNIFESP]; Gabriel Júnior, Alexandre [UNIFESP]; Nuccitelli, Barbara; Taliberti, Ben Hur; Von Mühlen, Carlos Alberto; Bichara, Carlos David Araújo; Santos, Cláudio Henrique Ramos dos; Bueno, Cleonice; Yano, Cristiane Martinez; Mangueira, Cristóvão Luis Pitangueiras; Carvalho, Darlene Gonçalves; Cardoso, Elizângela; Bonfá, Eloisa Silva Dutra de Oliveira; Araújo, Flávia Ikeda e; Rassi, Gustavo Gabriel; Mundim, Hugo Mendonça; Bendet, Izidro; Rego, Jozelia; Vieira, Lisiane Maria Enriconi dos Anjos; Andrade, Luiz Eduardo Coelho [UNIFESP]; Barbosa, Maria Ordália Ferro; Sugiyama, Mitiko; Santiago, Mittermayer Barreto; Slhessarenko, Natasha; Silva, Nilzio Antônio da; Francescantonio, Paulo Luiz Carvalho; Jarach, Renata; Suda, Roberto; Levy, Roger Abramino; Sampaio, Silvia Oliveira; Neves, Suzane Pretti Figueiredo; Cruvinel, Wilson de Melo [UNIFESP]; Santos, Wilton Silva dos [UNIFESP]; Nóbrega, Yanna Karla de Medeiros; Universidade Federal de São Paulo (UNIFESP); Fleury Medicina Diagnóstica Setor de Imunologia; AFIP-Medicina Laboratorial; Centro Imuno-Reumatológico de São Paulo; Padrão Laboratório Clínico; Universidade Federal de Uberlândia; HC UFU; PUCRS Faculdade de Medicina; UFPA; Laboratório Amaral Costa; CESEP/PA; NewLife Comércio de Produtos Laboratoriais; Universidade de São Paulo (USP); Universidade Católica de Goiás; Hospital Israelita Albert Einstein; Instituto Hermes Pardini; Biometrix Diagnóstica; UCG Departamento de Biomedicina; Laboratório Atalaia; Sérgio Franco Medicina Diagnóstica Setor de Imunoensaios; Universidade Federal de Goiás Faculdade de Medicina Hospital das Clínicas; Universidade do Sul de Santa Catarina; Universidade do Vale do Itajaí; Laboratório Médico Santa Luzia; Hospital e Maternidade e Jardim América Laboratórios Saúde; Hemagen Diagnósticos; Universidade Federal da Bahia; Fundação Bahiana para Desenvolvimento das Ciências; Hospital Santa Izabel; Universidade Federal de Mato Grosso; Universidade Federal de Goiás Faculdade de Medicina; Alka; Universidade do Estado do Rio de Janeiro; UERJ; Diagnósticos da América SA; Universidade Federal de Minas Gerais Faculdade de Medicina; Hospital Universitário de Brasília; União Educacional do Planalto Central; Centro Universitário Unieuro; Imunotech Sistemas Diagnósticos Importação e Exportação
OBJECTIVE: The Third Brazilian Consensus for autoantibodies Screening in HEp-2 cells had as purpose the evaluation of difficulties in the accomplishment of the 2nd Consensus recommendations that took place in the year of 2002, the discussion of strategies for quality control of the assay and the promotion of an update of the clinical associations of the several immunofluorescent patterns. METHODS:Several ANA experts from university centers and private laboratories in different areas in Brazil joined the workshop in Goiânia on 2008 April 13 and 14 with the purpose of discussing and approving the recommendations for standardization, interpretation and use of the test by physicians. Commercial representatives of different ANA slide brands were also invited as listeners to the workshop. RESULTS AND CONCLUSIONS: The 3rd Consensus emphasized the need for quality control in indirect immunofluorescent since there is a considerable heterogeneity of available microscopes and reagents. It also promoted adaptations in the previously approved terminology used to classify the different patterns and finally updated the clinical associations of the several patterns with the purpose of providing guidance for interpretation of the assay by clinical pathologists and assistant physicians.
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5' hypersensitive site-2 and fetal hemoglobin in Brazilians
(Marcel Dekker Inc, 1996-01-01) Figueirido, M. S.; Steinberg, M. H.; UNIV MISSISSIPPI; Universidade Federal de São Paulo (UNIFESP)
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5,10-methylenetetrahydrofolate reductase polymorphisms and acute lymphoblastic leukemia risk: A meta-analysis
(Amer Assoc Cancer Research, 2006-10-01) Pereira, Tiago da Veiga [UNIFESP]; Rudnicki, Martina; Pereira, Alexandre Costa; Pombo-de-Oliveira, Maria S.; Franco, Rendrik Franca; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); Inst Nacl Canc; Fleury Res Inst
There is evidence supporting a role for 5-10 methylenetetra-hydrofolate reductase (MTHFR) gene variants in acute lymphoblastic leukemia (ALL). To provide a more robust estimate of the effect of MTHFR polymorphisms on the risk of ALL, we did a meta-analysis to reevaluate the association between the two most commonly studied MTHFR polymorphisms (C677T and A1298C) and ALL risk. All case-control studies investigating an association between the C677T or A1298C polymorphisms and risk of ALL were included. We applied both fixed-effects and random-effects models to combine odds ratio (OR) and 95% confidence intervals (95% CI). Q-statistic was used to evaluate the homogeneity and both Egger and Begg-Mazumdar tests were used to assess publication bias. the meta-analysis of the C677T polymorphism and risk of childhood ALL included 13 studies with a total of 4,894 individuals. Under a fixed-effects model, the TT genotype failed to be associated with a statistically significant reduction of childhood ALL risk (TT versus CT + CC: OR, 0.88; 95% CI, 0.73-1.06; P = 0.18). However, individuals homozygous for the 677T allele exhibited a 2.2-fold decrease in risk of adult ALL (TT versus CT + CC: OR, 0.45; 95% CI, 0.26-0.77; P = 0.004). in both cases, no evidence of heterogeneity was observed. No association between the A1298C variant and susceptibility to both adult and childhood ALL was disclosed. Our findings support the proposal that the common genetic C677T polymorphism in the MTHFR contributes to the risk of adult ALL, but not to the childhood ALL susceptibility.
Acesso aberto (Open Access)
5-(4-Fluorophenyl)-2,2,6-trimethyl-4H-1,3-dioxin-4-one
(Wiley-Blackwell, 2009-07-01) Zukerman-Schpector, Julio; Vieira, Adriano Siqueira [UNIFESP]; Stefani, Helio Alexandre [UNIFESP]; Tiekink, Edward R. T.; Universidade Federal de São Carlos (UFSCar); Universidade Federal de São Paulo (UNIFESP)
The 1,3-dioxine ring in the title compound, C(13)H(13)FO(3), is in a half-boat conformation with the methyl-bonded C atom 0.612 (2) angstrom out of the plane defined by the remaining five atoms.
Somente Metadadados
5-Fluorouracil tópico para tratamento do condiloma genital em pacientes não imunocomprometidos
(Universidade Federal de São Paulo (UNIFESP), 2010) Batista, Claudio Sergio [UNIFESP]; Saconato, Humberto [UNIFESP]
Contexto; O condiloma acuminado e uma das formas mais comuns de Doenca Sexualmente Transmissivel (DST) e, como tal, um problema de Saúde Publica devido a associacao de Papillomavirus humano (HPV) com o cancer do colo uterino. A busca de um tratamento clinico efetivo, seguro, de baixo custo e auto-administrado deve ser procurada como forma de se multiplicar acoes no sentido de controlar esta DST. Objetivos: Avaliar a efetividade e seguranca do 5-Fluorouracil topico no tratamento do condiloma acuminado genital em individuos nao imunocomprometidos. Metodos: Revisao sistematica da Literatura com meta-analise de ensaio clinicos randomisados (RCT) segundo a metodologia da COLABORACAO COCHRANE. As bases de dados LILACS, referencias bibliograficas de estudos e anais de congressos. A qualidade dos estudos foi avaliada pelos criterios do Cochrane Handbook sendo incluidos somente estudos A e B pelos criterios de Schulz. Foram incluidos homens e mulheres com idade igual ou superior a 18 anos, com condiloma genital clinico ou subclinico. As intervencoes avaliadas foram 5-FU (0,5, 1%, 5%) versus placebo; 5-FU 5% versus Acido Metacresolsulfonico; 5-FU 5% versus Podofilina (2%, 4% e 25%); 5-FU 5% versus Laser de CO2; 5-FU 5% versus 5-FU 5% + Interferon α- 2a (baixa dose); 5-FU 5% versus + Interferon α- 2a (alta dose); 5-FU 5% versus 5-FU 5% + Laser de CO2 + Interferon α- 2a (alta dose); Laser de CO2 versus Laser de CO2 + 5-FU 5% e os desfechos foram cura, efeitos colaterais, falha ou resistencia ao tratamento, recorrencia da lesao e resposta parcial / melhora da lesao. Resultados: Foram encontrados 6 estudos , com 988 pacientes, 645 mulheres e 343 homens e 8 intervencoes. Dois estudos relataram perdas, mas, nenhum mencionou analise por intencao de tratar (ITT). 5-FU mostrou melhor resultado para cura que placebo ou nao tratamento [RR 0.39 (95% IC 0.23 a 0.67)], MCSA [RR 22.1 (95% IC 0.83 a 5.37)], e Podofilina 2%, 4% ou 25% [RR 1.26 (95% IC 0.86 a 1.82)]. Nao houve diferenca estatistica para falha do tratamento para 5-FU versus CO2 Laser [RR 0.69 (95% IC 0.43 a 1.11)], 5-FU + INFα-2a (baixa dose) [RR 1.02 (95% IC 0.87 a 1.119)]. O 5-FU mostrou pior resultado comparado com 5-FU + INFα-2a (alta dose) [RR 10.78 (95% IC 1.50 a 77.36)] e 5-FU + CO2 Laser INFα-2a (alta dose) [RR 7.97 (95% IC 2.87 a 22.13)]. Conclusao: Os estudos revisados sao heterogeneos em metodos e qualidade, e suas evidencias fracas, as taxas de cura sao variaveis e, embora, o 5-FU isolado tenha mostrado pior resultado que o 5-FU + INF α-2a (alta dose) e 5-FU + CO2 + INF α-2a (alta dose) entendemos que isto nao seja suficiente para descarta-lo como opcao de tratamento. Evidencias, ainda que pequenas, mostram que o tratamento topico de condiloma genital com 5-FU topico tem algum efeito terapeutico e, a despeito da pequena amostra e da heterogeneidade dos estudos , pode ser efetivo e seguro para tratamento do condiloma genital em casos selecionados num meio pobre como nosso
Somente Metadadados
The 5th International Conference on Magnetic Refrigeration, THERMAG V, in Grenoble
(Elsevier B.V., 2013-08-01) Egolf, Peter W.; Gama, Sergio [UNIFESP]; Univ Appl Sci Western Switzerland; Universidade Federal de São Paulo (UNIFESP)
Somente Metadadados
The A(1) receptor agonist R-Pia reduces the imbalance between cerebral glucose metabolism and blood flow during status epilepticus: Could this mechanism be involved with neuroprotection?
(Elsevier B.V., 2011-01-01) Silva, Lara Ribeiro [UNIFESP]; Nehlig, Astrid; Rosim, Fernanda Elisa [UNIFESP]; Vignoli, Thiago [UNIFESP]; Persike, Daniele Suzete [UNIFESP]; Ferrandon, Arielle; Sinigaglia-Coimbra, Rita [UNIFESP]; Silva Fernandes, Maria Jose da [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Strasbourg
It is well known that the uncoupling between local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF), i.e. decrease in LCBF rates with high LCGU, is frequently associated with seizure-induced neuronal damage. This study was performed to assess if the neuroprotective effect of the adenosinergic A(1) receptor agonist R-N-phenylisopropyladenosine (R-Pia) injected prior to pilocarpine is able to reduce the uncoupling between LCGU and LCBF during status epilepticus (SE). Four groups of rats were studied: Saline, Pilo, R-Pia + Saline and R-Pia + Pilo. for LCGU and LCBF studies, rats were subjected to autoradiography using [C-14]-2-deoxyglucose and [C-14]-iodoantypirine, respectively. Radioligands were injected 4 h after SE onset. Neuronal loss was evaluated by Fluorojade-B (FJB) at two time points after SE onset (24 h and 7 days). the results showed a significant increase in LCGU in almost all brain regions studied in the Pilo and R-Pia + Pilo groups compared to controls. However, in R-Pia pretreated rats, the uncoupling between LCGU and LCBF was moderated in a limited number of structures as substantia nigra pars reticulata and hippocampal formation rather in favor of hyperperfusion. Significant increases in LCBF were observed in the entorhinal cortex, thalamic nuclei, mammillary body, red nucleus, zona incerta, pontine nucleus and visual cortex. the neuroprotective effect of R-Pia assessed by FJB showed a lower density of degenerating cells in the hippocampal formation, piriform cortex and basolateral amygdala. in conclusion our data shows that the neuroprotective effect of R-Pia was accompanied by a compensatory metabolic input in brain areas involved with seizures generation. Published by Elsevier Inc.

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