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1.
Appl Opt ; 61(9): 2155-2164, 2022 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-35333241

RESUMO

The influence of both topography and optical constants on the optical reflection of bright-annealed AISI 430 ferritic stainless steel has been analyzed to correlate these characteristics with the occurrence of the unwanted haze effect in industrial products. This work reports the analysis of the total-integrated-scattering spectra of bright-annealed AISI 430 ferritic steel plates, on the basis of the microfacet model for the bidirectional reflectance function developed by He and Torrance [Siggraph '91, Proc. of the 18th Annual Conference on Computer Graphics and Interactive Techniques, (1991), p. 175]. Such an approach allows for modeling the optical reflection of these stainless-steel industrial products based on roughness parameters, root-mean square height, and autocorrelation length, derived from scale-limited topographic maps. The functional choice of the cutoff wavelength in the high-pass Gaussian filtering of the topographic map is proven critical. Additionally, optical constants n and k of the steels are estimated based on their total reflection spectra, measured in an 8°/di optical geometry. The results suggest that the haze effect could be due to a non-controlled increase in the thickness of the passive layer during the bright-annealing process.

2.
BMC Infect Dis ; 21(1): 1121, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34717584

RESUMO

BACKGROUND: More than 3 million infections were attributed to Chikungunya virus (CHIKV) in the 2014-2016 outbreak in Mexico, Central and South America, with over 500 deaths directly or indirectly related to this viral disease. CHIKV outbreaks are recurrent and no vaccine nor approved therapeutics exist to prevent or treat CHIKV infection. Reliable and robust diagnostic methods are thus critical to control future CHIKV outbreaks. Direct CHIKV detection in serum samples via highly specific and high affinity anti-CHIKV antibodies has shown to be an early and effective clinical diagnosis. METHODS: To isolate highly specific and high affinity anti-CHIKV, Chikungunya virions were isolated from serum of a patient in Veracruz, México. After purification and characterization via electron microscopy, SDS-PAGE and binding to well-characterized anti-CHIKV antibodies, UV-inactivated particles were utilized as selector in a solid-phase panning in combination with ALTHEA Gold Libraries™, as source of antibodies. The screening was based on ELISA and Next-Generation Sequencing. RESULTS: The CHIKV isolate showed the typical morphology of the virus. Protein bands in the SDS-PAGE were consistent with the size of CHIKV capsid proteins. UV-inactivated CHIKV particles bound tightly the control antibodies. The lead antibodies here obtained, on the other hand, showed high expression yield, > 95% monomeric content after a single-step Protein A purification, and importantly, had a thermal stability above 75 °C. Most of the antibodies recognized linear epitopes on E2, including the highest affinity antibody called C7. A sandwich ELISA implemented with C7 and a potent neutralizing antibody isolated elsewhere, also specific for E2 but recognizing a discontinuous epitope, showed a dynamic range of 0.2-40.0 mg/mL of UV-inactivated CHIKV purified preparation. The number of CHIKV particles estimated based on the concentration of E2 in the extract suggested that the assay could detect clinically meaningful amounts of CHIKV in serum. CONCLUSIONS: The newly discovered antibodies offer valuable tools for characterization of CHIKV isolates. Therefore, the strategy here followed using whole viral particles and ALTHEA Gold Libraries™ could expedite the discovery and development of antibodies for detection and control of emergent and quickly spreading viral outbreaks.


Assuntos
Febre de Chikungunya , Vírus Chikungunya , Anticorpos Neutralizantes , Anticorpos Antivirais , Febre de Chikungunya/diagnóstico , Humanos , Proteínas do Envelope Viral
3.
Rev Esp Anestesiol Reanim ; 56(1): 27-30, 2009 Jan.
Artigo em Espanhol | MEDLINE | ID: mdl-19284125

RESUMO

OBJECTIVE: To evaluate the effect of prehydration with hydroxyethyl starch 130/0.4 (Voluven) compared to lactated Ringer solution in laparoscopic cholecystectomy. PATIENTS AND METHODS: We performed a randomized single-blind clinical trial on patients classified as ASA 1 and 2. The exclusion criteria were hypertension, kidney failure, treatment with diuretics or other antihypertensive drugs, diabetes, and use of nonsteroidal anti-inflammatory drugs. Balanced general anesthesia with remifentanil and sevoflurane was used. The total volume of administered fluids (including prehydration) was 2 mL x kg(-1) x h(-1) fasting plus 5 mL x kg(-1) x h(-1) during surgery. Group 1 was prehydrated 30 minutes before surgery with 500 mL of lactated Ringer solution in group 1; in group 2 the same quantity of Voluven was used. Ringer solution was used in both groups to provide additional fluids. Blood pressure was kept within 20% above or below baseline values. Standard anesthetic monitoring was performed. Intraoperative diuresis and creatinine clearance were recorded. The groups were compared using the t test; a P value of 05 or less was considered significant. RESULTS: Twenty-nine patients were enrolled in the study. Diuresis and creatinine clearance were significantly higher in the group that received prehydration with Voluven. The mean (SD) creatinine clearance rate was 176.44 (1433) mL x min(-1) in group 1 and 61.90 (6.6) mL x min(-1) in group 2 (P = .036). The mean volume of urine excreted was 1.71 (0.06) mL x kg(-1) x h(-1) in group 1 and 0.47 (0.02) mL x kg(-1) x h(-1) in group 2 (P = .017). CONCLUSION: Prehydration with Voluven can be an effective measure for protecting renal function against the adverse effects of pneumoperitoneum in laparoscopic surgery.


Assuntos
Colecistectomia Laparoscópica , Diurese/efeitos dos fármacos , Hidratação , Derivados de Hidroxietil Amido/uso terapêutico , Taxa de Depuração Metabólica/efeitos dos fármacos , Pneumoperitônio Artificial/efeitos adversos , Pré-Medicação , Circulação Renal/efeitos dos fármacos , Adulto , Creatinina/sangue , Feminino , Humanos , Derivados de Hidroxietil Amido/administração & dosagem , Derivados de Hidroxietil Amido/farmacologia , Soluções Isotônicas/administração & dosagem , Soluções Isotônicas/farmacologia , Soluções Isotônicas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Lactato de Ringer
4.
Rev. esp. anestesiol. reanim ; 56(1): 27-30, ene. 2009. tab
Artigo em Espanhol | IBECS | ID: ibc-59467

RESUMO

OBJETIVO: Valorar el efecto sobre la función renal dela prehidratación con hidroxietil almidón 130/0,4 (Voluven®) frente al Ringer Lactato en las colecistectomíaslaparoscópicas.PACIENTES Y MÉTODOS: Ensayo clínico aleatorizadosimple ciego en pacientes ASA I, II. Criterios de exclusión:hipertensión arterial, insuficiencia renal, tratamientocon diuréticos u otros antihipertensivos, diabéticos,uso de anti-inflamatorios no esteroideos. Anestesiageneral balanceada basada en remifentanilo-sevofluorano.Volumen total de fluidos administrados: (incluida laprehidratación): 2 mL Kg–1 h–1 ayuno + 5 mL Kg–1 h–1 deintervención. Prehidratación 30 minutos antes de laintervención con 500 mL de Ringer Lactado (RL) en elGrupo I y con la misma cantidad de Voluven® en el GrupoII. Resto de la fluidoterapia basada en Ringer Lactatoen ambos grupos. Mantenimiento de la presión arterialmedia ± 20% de los valores iniciales. Monitorizaciónanestésica habitual. Medida de diuresis intraoperatoriay aclaramiento de creatinina de diuresis intraoperatoria(ClCr). Comparación de grupos mediante t Student conun nivel de significación p ≤ 0,05.RESULTADOS: Se incluyeron 29 pacientes. Las diuresisy el aclaramiento de creatinina obtenidos fueron mayoresde forma estadísticamente significativa en el grupoen el que se realizó la prehidratación con Voluven®. ClCr(mL min–1) GRUPO I: 176,44 ± 14,33, GRUPO II:61,90 ± 6,6 (p = 0,036); Diuresis (mL Kg–1 h–1) GRUPO I:1,71 ± 0,06, GRUPO II 0,47 ± 0,02 (p = 0,017).CONCLUSIONES: La prehidratación con Voluven® puedeser una medida eficaz en la protección de la función renalfrente a los efectos adversos del neumoperitoneo en lacirugía laparoscópica (AU)


OBJETIVE: To evaluate the effect of prehydration withhydroxyethyl starch 130/0.4 (Voluven) compared tolactated Ringer solution in laparoscopic cholecystectomy.PATIENTS AND METHODS: We performed a randomizedsingle-blind clinical trial on patients classified as ASA 1and 2. The exclusion criteria were hypertension, kidneyfailure, treatment with diuretics or other antihypertensivedrugs, diabetes, and use of nonsteroidal anti-inflammatorydrugs. Balanced general anesthesia with remifentanil andsevoflurane was used. The total volume of administeredfluids (including prehydration) was 2 mL·kg-1·h-1 fastingplus 5 mL·kg-1·h-1 during surgery. Group 1 wasprehydrated 30 minutes before surgery with 500 mL oflactated Ringer solution in group 1; in group 2 the samequantity of Voluven was used. Ringer solution was used inboth groups to provide additional fluids. Blood pressurewas kept within 20% above or below baseline values.Standard anesthetic monitoring was performed.Intraoperative diuresis and creatinine clearance wererecorded. The groups were compared using the t test; a Pvalue of 05 or less was considered significant.RESULTS: Twenty-nine patients were enrolled in thestudy. Diuresis and creatinine clearance weresignificantly higher in the group that receivedprehydration with Voluven. The mean (SD) creatinineclearance rate was 176.44 (14.33) mL·min-1 in group 1and 61.90 (6.6) mL·min-1 in group 2 (P=.036). The meanvolume of urine excreted was 1.71 (0.06) mL·kg-1·h-1 ingroup 1 and 0.47 (0.02) mL·kg-1·h-1 in group 2 (P= .017).CONCLUSION: Prehydration with Voluven can be aneffective measure for protecting renal function againstthe adverse effects of pneumoperitoneum in laparoscopicsurgery (AU)


Assuntos
Humanos , Derivados de Hidroxietil Amido/uso terapêutico , Laparoscopia/métodos , Hidratação/métodos , Testes de Função Renal , Insuficiência Renal/prevenção & controle , Rim/fisiologia
5.
Biosystems ; 61(2-3): 125-31, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11716972

RESUMO

The Kabat database is the source of information par excellence on antibody sequences. In 1995, we developed an interface with the Kabat database, called VIR. VIR has been very useful in conducting studies aiming to find structure-function relationships in antibodies. Here we report a new version adapted to the World Wide Web, called VIR.II. VIR.II allows searches by type of chain (V(H) or V(L)), by species, and by specificity. The species are selected using a pulldown menu, whereas the specificities can be selected from a list containing the unique specificities reported in the Kabat database. These facilities avoid mistakes and redundancies in the searches. Another feature, and probably the most important one, is that VIR.II introduces a classification of specificities in terms of the chemical and biochemical nature of the antigen, like anti-protein, anti-peptide, anti-hapten, etc. This classification has been useful in discovering patterns in the antigen-binding site of antibodies that correlate with the type of antigen the antibody interacts with. To illustrate this, while showing the capabilities of VIR.II, we analyze all the murine anti-peptide and anti-protein antibody sequences compiled as of July, 2000 in the Kabat database.


Assuntos
Anticorpos/genética , Bases de Dados de Proteínas , Sequência de Aminoácidos , Animais , Especificidade de Anticorpos , Internet , Camundongos , Interface Usuário-Computador
6.
Proteins ; 45(3): 199-206, 2001 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-11599023

RESUMO

Forty unique murine antibody-antigen complexes determined at 2.5 A or less resolution are analyzed to determine whether the residues in direct contact with the antigen are modified by somatic hypermutation. This was done by taking advantage of the recent characterization of the pool of Vkappa germline genes of the mouse. The average number of residues in contact with the antigen in the V(L) gene, which contains the CDRL-1, CDRL-2, and all but one residue of CDRL-3, was six. The average number of somatic mutations was similar (around five). However, as many as 53% of the antibodies did not show somatic replacements of residues in contact with the antigen. Another 28% had only one. Overall, the frequency of antibodies with increasing number of somatic replacements in residues in contact with the antigen decreased exponentially. A possible explanation of this finding is that mutations in the contacting residues have an adverse effect on the antigen-antibody interaction. This implies that most of the observed mutations are those remaining after negative (purifying) selection. Therefore, efficient strategies of site-directed mutagenesis to improve the affinity of antibodies should be focused on residues other than those directly interacting with the antigen.


Assuntos
Antígenos/química , Antígenos/metabolismo , Imunoglobulinas/química , Imunoglobulinas/genética , Hipermutação Somática de Imunoglobulina/genética , Animais , Afinidade de Anticorpos/genética , Complexo Antígeno-Anticorpo/química , Complexo Antígeno-Anticorpo/genética , Sítios de Ligação de Anticorpos/genética , Evolução Molecular Direcionada , Mutação em Linhagem Germinativa/genética , Imunoglobulinas/metabolismo , Camundongos , Mutagênese Sítio-Dirigida/genética , Ligação Proteica/genética , Mapeamento de Interação de Proteínas/métodos , Relação Estrutura-Atividade
7.
Curr Pharm Biotechnol ; 2(3): 217-23, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11530876

RESUMO

Phage display is a powerful technology for selecting and engineering peptides and proteins expressed on the surface of filamentous bacteriophage. The advantages of phage display technology over other research tools and its' great potential have been demonstrated by successful application of phage display in diverse fields of biomedical/clinical research. In this review we will describe some recent developments in phage display, including new expression vectors, display formats, bioselection strategies and applications in pharmaceutical biotechnology. We highlight some important applications of phage display to identify disease- and pathogen-specific biomolecules, making particular emphasis on development of phage display-derived preventive and therapeutic vaccines.


Assuntos
Biblioteca de Peptídeos , Peptídeos/farmacologia , Vacinas de Subunidades Antigênicas/farmacologia , Animais , Desenho de Fármacos , Humanos , Peptídeos/química , Peptídeos/genética , Vacinas de Subunidades Antigênicas/genética
8.
Rev Esp Cardiol ; 54(4): 518-21, 2001 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-11282059

RESUMO

Catheter-induced mechanical trauma to accessory pathways is an infrequent, usually transitory phenomenon related to manipulation of the ablation catheter. We describe a patient with Wolff-Parkinson-White syndrome due to a midseptal accessory pathway with recurrent episodes of paroxysmal tachycardias under antiarrhythmic treatment. During the diagnostic electrophysiological study coinciding with manipulation of the His catheter (5 French), mechanical trauma to the accessory pathways occurred, with preexcitation not being recovered in the midterm follow up (28 months). This is a exceptional case demonstrating the complexity of the decision making (expectant or rescue ablation) following accidental catheter-induced mechanical trauma.


Assuntos
Cateterismo Cardíaco/efeitos adversos , Síndrome de Wolff-Parkinson-White/terapia , Adulto , Eletrodos , Humanos , Masculino , Indução de Remissão
10.
Rev Esp Cardiol ; 51(10): 844-6, 1998 Oct.
Artigo em Espanhol | MEDLINE | ID: mdl-9834635

RESUMO

We report a case of spontaneous dissection of right coronary artery diagnosed in a 31-year-old woman in the postpartum period, presenting with prolonged angina and ST segment elevation in the ECG, a rare manifestation of this extremely uncommon anatomico-clinic entity. We described the clinical presentation, the findings derived from transthoracic echocardiography and coronary arteriography, and the clinical course with medical therapy.


Assuntos
Dissecção Aórtica/diagnóstico , Aneurisma Coronário/diagnóstico , Transtornos Puerperais/diagnóstico , Adulto , Cateterismo Cardíaco , Angiografia Coronária , Ecocardiografia , Eletrocardiografia , Feminino , Humanos
11.
Proteins ; 32(4): 399-413, 1998 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-9726412

RESUMO

A new method for calculating the total conformational free energy of proteins in water solvent is presented. The method consists of a relatively brief simulation by molecular dynamics with explicit solvent (ES) molecules to produce a set of microstates of the macroscopic conformation. Conformational energy and entropy are obtained from the simulation, the latter in the quasi-harmonic approximation by analysis of the covariance matrix. The implicit solvent (IS) dielectric continuum model is used to calculate the average solvation free energy as the sum of the free energies of creating the solute-size hydrophobic cavity, of the van der Waals solute-solvent interactions, and of the polarization of water solvent by the solute's charges. The reliability of the solvation free energy depends on a number of factors: the details of arrangement of the protein's charges, especially those near the surface; the definition of the molecular surface; and the method chosen for solving the Poisson equation. Molecular dynamics simulation in explicit solvent relaxes the protein's conformation and allows polar surface groups to assume conformations compatible with interaction with solvent, while averaging of internal energy and solvation free energy tend to enhance the precision. Two recently developed methods--SIMS, for calculation of a smooth invariant molecular surface, and FAMBE, for solution of the Poisson equation via a fast adaptive multigrid boundary element--have been employed. The SIMS and FAMBE programs scale linearly with the number of atoms. SIMS is superior to Connolly's MS (molecular surface) program: it is faster, more accurate, and more stable, and it smooths singularities of the molecular surface. Solvation free energies calculated with these two programs do not depend on molecular position or orientation and are stable along a molecular dynamics trajectory. We have applied this method to calculate the conformational free energy of native and intentionally misfolded globular conformations of proteins (the EMBL set of deliberately misfolded proteins) and have obtained good discrimination in favor of the native conformations in all instances.


Assuntos
Simulação por Computador , Modelos Químicos , Conformação Proteica , Proteínas/química , Dobramento de Proteína , Solventes , Termodinâmica
12.
Clin Immunol Immunopathol ; 86(3): 305-9, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9557164

RESUMO

A random heptapeptide phage-displayed library was screened with two serum samples from autoimmune thrombocytopenic purpura (AITP) patients to address the repertoire of autoantigenic epitopes involved in platelet destruction. We obtained a panel of affinity-selected phage clones that have been shown to react in enzyme-linked immunosorbent assay with autoantibodies from other AITP patients. None of the peptides obtained has been described previously as possibly being an epitope for antiplatelet antibodies, and the majority of them did not show any homology with known platelet glycoproteins. We conclude that peptides identified in this study could represent discontinuous epitopes or mimotopes of natural autoantigens. Also, they could be present in still-unknown proteins involved in AITP pathogenesis.


Assuntos
Autoantígenos/química , Epitopos/química , Púrpura Trombocitopênica Idiopática/imunologia , Sequência de Aminoácidos , Autoanticorpos/sangue , Plaquetas/imunologia , Mapeamento de Epitopos , Feminino , Humanos , Técnicas In Vitro , Masculino , Biblioteca de Peptídeos
13.
Immunogenetics ; 47(5): 355-63, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9510553

RESUMO

Although human and mouse antibodies are similar when one considers their diversification strategies, they differ in the extent to which kappa and lambda light chains are present in their respective variable light chain repertoires. While the Igk-V germline genes are preponderant in mice (95% or more), they comprise only 60% in humans. This may account for differences in the structural repertoire encoded in the Igk-V germline genes of these species. However, this subject has not been properly investigated, partially because a systematic structural characterization of the mouse Igk-V germline genes has not been undertaken. In the present study we compiled all available information on mouse Igk-V germline genes to characterize their structural repertoire. As expected, comparison with the structural repertoire of human Igk-V germline genes indicates differences. The most interesting is that the mouse Igk-V germline gene repertoire is more diverse in structural terms than its human counterpart: the mouse encodes seven canonical structure classes (combination of canonical structures in L1 and L3). In contrast, the human encodes only four. Analysis of the evolutionary relationships of human and mouse Igk-V germline genes led us to propose that the difference reflects a strategy of mice to compensate for the small lambda chain contribution to the repertoire of their variable light chains.


Assuntos
Diversidade de Anticorpos/genética , Evolução Molecular , Genes de Imunoglobulinas/genética , Células Germinativas/metabolismo , Região Variável de Imunoglobulina/genética , Cadeias kappa de Imunoglobulina/genética , Sequência de Aminoácidos , Animais , Dosagem de Genes , Genes/genética , Células Germinativas/imunologia , Humanos , Camundongos , Dados de Sequência Molecular , Família Multigênica/genética , Filogenia , Pseudogenes/genética , Alinhamento de Sequência
14.
Rev Esp Cardiol ; 50(3): 145-56, 1997 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-9132874

RESUMO

In the last few years the has been an enormous development in noninvasive testing in the field of clinical cardiology. In fact, excellent monographs on each one of these techniques have been published elsewhere, but fewer publications exist that treat the topic of their indications and use in an integrated way, except for in the most common clinical situations. In this paper, the treatment of patients who present chest pain, stable and unstable angina is discussed, including the study of postinfarction patients. Furthermore, the role of noninvasive tests in the detection of coronary heart disease in women and in patients with left bundle branch block is thoroughly analyzed; as well as their usefulness after surgical or percutaneous coronary revascularization and in patients with peripheral vascular disease.


Assuntos
Doença das Coronárias/diagnóstico , Angina Pectoris/diagnóstico , Angina Instável/diagnóstico , Angioplastia Coronária com Balão , Dor no Peito/diagnóstico , Doença das Coronárias/diagnóstico por imagem , Diagnóstico Diferencial , Ecocardiografia , Teste de Esforço , Feminino , Bloqueio Cardíaco/diagnóstico , Humanos , Masculino , Revascularização Miocárdica , Tomografia Computadorizada de Emissão de Fóton Único
15.
Rev Esp Cardiol ; 50(2): 105-10, 1997 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-9091996

RESUMO

INTRODUCTION AND OBJECTIVES: It has been shown that the delta P/delta t index, derived from the continuous Doppler mitral regurgitation signal correlates strongly with dP/dt. This study evaluates the feasibility, reproducibility and correlation of the index with ejection fraction and other conventional echocardiographic parameters. MATERIAL AND METHODS: One hundred and ten patients with mitral regurgitation demonstrated by colour Doppler were studied. delta P/delta t were calculated by the ratio between the interval of pression between two points of the Doppler signal (-1 and -3 m/s; 32 mmHg, applying the modified Bernouilli equation) and the interval of time (s) which separates both. Ejection fraction was measured in 70 patients by non-echocardiographic methods (isotopic ventriculography, n = 52, and angiography, n = 18). RESULTS: The index was feasible in 91 cases, the variability of intra and interobserver was 5% and 7% respectively. The correlation between delta P/delta t and ejection fraction was significant although weak (r = 0.59; p < 0.001; n = 70). It was better in the group of dilated idiopathic myocardiopathy (r = 0.72; p < 0.001; n = 18) than in the group of myocardial infarction (r = 0.54; p < 0.01; n = 25). No significant correlation was founded in the cases with mitral rheumatic valvulopathy. Regarding to the echocardiographic parameters, the best correlation was obtained with end systolic diameter (r = -0.64; p < 0.001; n = 49). Finally, a value of delta P/delta t < 1,000 mmHg/s predicted the existence of left ventricular systolic dysfunction with high accuracy (84%), sensitivity (80%) and specificity (92%). CONCLUSIONS: High feasibility when mitral regurgitation exists, adequate reproducibility and heightened precision in diagnosing left ventricular systolic dysfunction, are characteristics which make delta P/delta t useful in the echocardiographic routine practice.


Assuntos
Ecocardiografia Doppler em Cores , Disfunção Ventricular Esquerda/diagnóstico por imagem , Idoso , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/fisiopatologia , Interpretação Estatística de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/fisiopatologia , Contração Miocárdica , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Variações Dependentes do Observador , Volume Sistólico , Disfunção Ventricular Esquerda/fisiopatologia
16.
Int J Clin Pharmacol Ther ; 35(1): 19-23, 1997 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9021437

RESUMO

AIM: The question regarding the minimal effective oral dose of fenoterol remains unanswered. The present study was undertaken to compare the therapeutic effects of sustained release theophylline and a conventional low dose oral fenoterol in patients with asthma. PATIENTS AND METHODS: A double-blind, double-dummy, randomized, 2-phase, cross-over comparison between sustained-release theophylline (SR-T) and oral fenoterol 2.5 mg 3 times daily in 21 patients with stable bronchial asthma (mean age 51 years) was conducted. Each drug was administered for a 2-week period. All patients qualified with a > or = 15% reversibility in forced expiratory volume in 1 second (FEV1) following 200 micrograms of inhaled salbutamol. Spirometric tests and body plethysmography were done at baseline and at the end of each treatment period. Blood was drawn for routine laboratory analysis and serum theophylline concentration. During each treatment period the patient kept a diary of symptoms and the concurrent use of inhaled salbutamol was recorded. RESULTS: During SR-T administration trough serum concentrations were 12.9 (1.5) mg/l mean (+/- SEM). SR-theophylline produced greater maximal changes in all parameters measured: FEV1, forced vital capacity, and specific airway resistance from the pretreatment and fenoterol phase, while fenoterol caused significant changes in none of the test variables. Patients showed an overall preference for SR-T over fenoterol (p < 0.05). CONCLUSIONS: Thus, 2.5 mg of fenoterol at 8-hour intervals did not prove to be an effective alternative to sustained release theophylline for management of patients with asthma. An appropriate dosing schedule for fenoterol needs to be redefined.


Assuntos
Asma/tratamento farmacológico , Broncodilatadores/administração & dosagem , Fenoterol/administração & dosagem , Teofilina/administração & dosagem , Administração por Inalação , Administração Oral , Adulto , Albuterol/administração & dosagem , Asma/fisiopatologia , Estudos Cross-Over , Preparações de Ação Retardada , Método Duplo-Cego , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade
17.
Int Immunol ; 9(12): 1801-15, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9466308

RESUMO

Variable genes of human Ig are classified in families and clans which reflect the early events of gene duplication in the evolution of the locus. This organization in multiple copies of variable genes plus the somatic processes of recombination and hypermutation allows the immune system to generate an antibody repertoire of great diversity. At present the role that somatic processes play in the generation of that diversity is understood with some detail. It is a matter of hard controversy, however, which selective pressures have shaped the evolution of the germline genes of Ig and, consequently, what the role of this germline component in the generation of the antibody diversity actually is. Previous studies of our group have showed that the structural repertoire of Ig-determined by the canonical structures-is an important factor to determine the recognition properties of the antibodies. Complete knowledge of the sequences of the human V(H) and Vkappa loci is available to analyze the evolution of the structural repertoire of these loci. Two phylogenetic gene trees were built from the functional germline genes and the evolution of the structural repertoire was studied. We report that for both loci the canonical structures are not randomly distributed within the tree. Conversely, it is shown that the evolution of the structural repertoire follows a gradual process of diversification. This indicates a correlation between the evolution of genes and the structural repertoire, although important differences are found in the patterns of evolution of the structural repertoire between V(H) and Vkappa. Based on those results we propose a primordial structural repertoire for V(H) and Vkappa. The general properties and an outline of the three-dimensional structure of this primordial repertoire are given.


Assuntos
Evolução Molecular , Genes de Imunoglobulinas , Cadeias Pesadas de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética , Cadeias kappa de Imunoglobulina/genética , Sequência de Aminoácidos , Humanos , Dados de Sequência Molecular , Conformação Proteica , Homologia de Sequência de Aminoácidos
18.
Mol Immunol ; 34(16-17): 1199-214, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9566767

RESUMO

Although human and murine antibodies are similar when considering their diversification strategies, they differ in the proportion by which kappa and lambda type chains are present in their receptive V, repertoires. It has been shown that this difference implies a divergence in the structural repertoire of the kappa and lambda genes of these species. Nonetheless, the differences in VH have not been systematically studied. In this paper a systematic characterization of the VH structural repertoire of mice is made, so that a comparison with the VH structural repertoire of humans, described in detail elsewhere, could be properly accomplished. Our study shows the structural repertoire of mice to be dominated by canonical structure class 1-2 (approximately 60%), while in humans the dominant one is class 1-3 (approximately 40%). Analysis of the evolutionary relationships between human and mice suggest that this divergence may have a functional meaning. The implications of such findings are discussed.


Assuntos
Genes de Imunoglobulinas , Imunidade/genética , Cadeias Pesadas de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética , Sequência de Aminoácidos , Animais , Humanos , Camundongos , Dados de Sequência Molecular , Alinhamento de Sequência
19.
J Mol Evol ; 43(6): 678-84, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8995065

RESUMO

The antibodies of known three-dimensional structure exhibit a definite number of conformations (canonical structures) for five of six hypervariable loops. In the present study it was found that approximately 85% of the immunoglobulin sequences analyzed fall into a small number of canonical structure combinations, representing only 3% of the total possible. These structures were classified into six distinct groups, depending on the type of antigen with which they interact. Within each loop, the positions responsible for maintaining these canonical structures show a use frequency of amino acids that fits an inverse power law, whereas the use frequency of the amino acids responsible for the detailed antigenic specificity follows an exponential distribution. We propose an evolutionary interpretation that connects these data, using the fact that the inverse power law is generated by statistical processes of the type that yield a wealth curve and the fact that exponential distribution is generated by processes that are not biased by past history.


Assuntos
Anticorpos/química , Antígenos/química , Evolução Molecular , Imunoglobulinas/química , Modelos Moleculares , Animais , Anticorpos/classificação , Anticorpos/imunologia , Antígenos/metabolismo , Reações Cruzadas , Imunoglobulinas/fisiologia , Camundongos , Modelos Biológicos , Conformação Proteica , Relação Estrutura-Atividade
20.
Immunol Lett ; 49(3): 185-9, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8739315

RESUMO

The screening of a cDNA library of Taenia crassiceps revealed a clone designated KETc7 that induced high levels of protection against murine cysticercosis in previous experiments. The molecular structure of the deduced 100-amino acid sequence of the corresponding proline-rich polypeptide was studied to detect potentially immunologically active epitopes. Several candidate epitopes were identified, three of which were synthesized by solid-phase peptide synthesis and used as antigens in enzyme-linked immunosorbent assay (ELISA) for detection of specific antibodies in a selected panel of sera from mice infected with Taenia crassiceps and pigs infected with Taenia solium, as well as in the serum and cerebrospinal fluid of human patients with neurocysticercosis. The three peptides detected antibodies in serum from all infected mice. Seven of nine sera from patients with neurocysticercosis reacted strongly with peptide GK-3, and four of them with peptides GK-1 and GK-2. A lower reactivity was observed in sera from experimentally infected pigs. Peptide GK-3 reacted also with 45 out of 77 cerebrospinal fluids (CSF) from patients with confirmed neurocysticercosis and with 14 out of 68 CSF from control patients with other neurological disorders. This is the first report on synthetic peptides that are prominent in the humoral response of murine, porcine and human cysticercosis. Their identification implies finer molecular tools in the exploration of this form of host-parasite relationship, as well as hints to their application in immunodiagnosis and in vaccine design.


Assuntos
Antígenos de Helmintos/química , Cisticercose/imunologia , Proteínas de Helminto/imunologia , Taenia/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Anti-Helmínticos/imunologia , Humanos , Camundongos , Dados de Sequência Molecular , Peptídeos/química , Peptídeos/imunologia , Suínos
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