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1.
Rev Colomb Obstet Ginecol ; 72(3): 298-306, 2021 09 30.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34851572

RESUMO

Objective: To report the case of a pregnant woman with mirror syndrome associated with non-compaction cardiomyopathy in the mother and the fetus, in which antenatal medical treatment provided to the mother resulted in a favorable perinatal maternal outcome. Case presentation: A 16-year old primigravida with 33 weeks of gestation referred from a Level I institution to a private Level IV center in Medellín, Colombia, because of a finding of fetal hydrops on obstetric ultrasound. During hospitalization, the patient showed clinical and ultrasonographic signs of heart failure (dyspnea, edema and hypoxemia), with the diagnosis of hydrops fetalis (mirror syndrome) also confirmed. Diuretic treatment with furosemide was initiated in the mother, with subsequent improvement of the maternal condition as well as of the fetal edema. During the subacute postpartum period in the hospital, the presence of non-compaction cardiomyopathy was confirmed on cardiac nuclear magnetic resonance imaging in both the mother and the newborn. After discharge in adequated condition, they were included in the cardiovascular follow-up program for heart failure and congenital heart disease, respectively. Conclusion: A case of mirror syndrome associated with maternal and fetal non-compaction cardiomyopathy is presented. There is a limited number of reports on mirror syndrome due to cardiac anomalies (maternal and fetal), with weak treatment descriptions, pointing to the need for research in this area. It would be important to consider the diagnosis of non-compaction cardiomyopathy in fetuses with hydrops unrelated to isoimmunization or cardiac dysfunction, and approach these cases from a multi-disciplinary perspective.


Objetivo: reportar el caso de una gestante con síndrome en espejo asociada a miocardiopatía no compactada, tanto en la madre como el feto, en los que el tratamiento médico antenatal en la madre llevó a un resultado materno perinatal favorable. Presentación del caso: se describe el caso de una primigestante de 16 años, con 33 semanas de embarazo, remitida desde una institución de primer nivel de atención a una institución privada de cuarto nivel en la ciudad de Medellín, Colombia, por presentar feto con hidropesía en ultrasonido obstétrico de control. Durante la hospitalización, la paciente presentó signos clínicos y ecocardiográficos de falla cardiaca (disnea, edema e hipoxemia), a la vez que se confirmó el diagnóstico de Hydrops fetalis (síndrome en espejo). Se instauró tratamiento diurético con furosemida en la madre, logrando mejoría del cuadro materno y del edema fetal. En el puerperio mediato hospitalario se confirmaron la presencia de miocardiopatía no compactada en la resonancia magnética nuclear cardiaca, tanto de la madre como del recién nacido. Ambos egresaron en adecuadas condiciones y fueron vinculados al programa de seguimiento cardiovascular: falla cardiaca y de cardiopatía congénitas, respectivamente. Conclusión: se presenta un caso de síndrome en espejo asociado a miocardiopatía no compactada materna y fetal. Es limitado el número de reportes de síndrome en espejo por anomalías cardiacas (maternas y fetales) y pobre la descripción de los tratamientos realizados que surgen como temas a investigar. Sería importante considerar el diagnóstico de MNC en fetos con hidropesía no asociados a isoinmunización y con disfunción cardiaca, así como su atención por equipos multidisciplinarios.


Assuntos
Cardiomiopatias , Edema , Adolescente , Cardiomiopatias/diagnóstico por imagem , Feminino , Feto , Humanos , Hidropisia Fetal/diagnóstico por imagem , Recém-Nascido , Mães , Gravidez
2.
Rev. colomb. obstet. ginecol ; 72(3): 298-306, July-Sept. 2021. graf
Artigo em Espanhol | LILACS | ID: biblio-1351954

RESUMO

Objetivo: reportar el caso de una gestante con síndrome en espejo asociada a miocardiopatía no compactada (MNC), tanto en la madre como el feto, en los que el tratamiento médico antenatal en la madre llevó a un resultado materno perinatal favorable. Presentación del caso: se describe el caso de una primigestante de 16 años, con 33 semanas de embarazo, remitida desde una institución de primer nivel de atención a una institución privada de cuarto nivel en la ciudad de Medellín, Colombia, por presentar feto con hidropesía en ultrasonido obstétrico de control. Durante la hospitalización, la paciente presentó signos clínicos y ecocardiográficos de falla cardiaca (disnea, edema e hipoxemia), a la vez que se confirmó el diagnóstico de Hydrops fetalis (síndrome en espejo). Se instauró tratamiento diurético con furosemida en la madre, logrando mejoría del cuadro materno y del edema fetal. En el puerperio mediato hospitalario se confirmaron la presencia de miocardiopatía no compactada en la resonancia magnética nuclear cardiaca, tanto de la madre como del recién nacido. Ambos egresaron en adecuadas condiciones y fueron vinculados al programa de seguimiento cardiovascular: falla cardiaca y de cardiopatía congénitas, respectivamente. Conclusión: se presenta un caso de síndrome en espejo asociado a miocardiopatía no compactada materna y fetal. Es limitado el número de reportes de síndrome en espejo por anomalías cardiacas (maternas y fetales) y pobre la descripción de los tratamientos realizados que surgen como temas a investigar. Sería importante considerar el diagnóstico de MNC en fetos con hidropesía no asociados a isoinmunización y con disfunción cardiaca, así como su atención por equipos multidisciplinarios.


ABSTRACT Objective: To report the case of a pregnant woman with mirror syndrome associated with noncompaction cardiomyopathy in the mother and the fetus, in which antenatal medical treatment provided to the mother resulted in a favorable perinatal maternal outcome. Case presentation: A 16-year old primigravida with 33 weeks of gestation referred from a Level I institution to a private Level IV center in Medellín, Colombia, because of a finding of fetal hydrops on obstetric ultrasound. During hospitalization, the patient showed clinical and ultrasonographic signs of heart failure (dyspnea, edema and hypoxemia), with the diagnosis of hydrops fetalis (mirror syndrome) also confirmed. Diuretic treatment with furosemide was initiated in the mother, with subsequent improvement of the maternal condition as well as of the fetal edema. During the subacute postpartum period in the hospital, the presence of non-compaction cardiomyopathy was confirmed on cardiac nuclear magnetic resonance imaging in both the mother and the newborn. After discharge in adequated condition, they were included in the cardiovascular follow-up program for heart failure and congenital heart disease, respectively. Conclusion: A case of mirror syndrome associated with maternal and fetal non-compaction cardiomyopathy is presented. There is a limited number of reports on mirror syndrome due to cardiac anomalies (maternal and fetal), with weak treatment descriptions, pointing to the need for research in this area. It would be important to consider the diagnosis of non-compaction cardiomyopathy in fetuses with hydrops unrelated to isoimmunization or cardiac dysfunction and approach these cases from a multidisciplinary perspective.


Assuntos
Humanos , Feminino , Gravidez , Recém-Nascido , Lactente , Adolescente , Doenças Placentárias , Hidropisia Fetal , Miocárdio Ventricular não Compactado Isolado , Cardiomiopatias , Síndrome , Edema , Feto
3.
Chem Biol Drug Des ; 98(1): 182-191, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33982434

RESUMO

In vivo receptor targeting with radiolabelled peptide-based probes is an attractive approach for the development of novel radiotracers for molecular imaging. This work presents the development and characterization of two novel neuropeptide Y analogues labelled with a positron emitter 68 Ga, for potential use in breast cancer imaging. Both analogues share the same amino acid sequence and were derivatized with NOTA through either a lysine linker (L1) or an acetylated lysine (L2). In both cases, a single product with radiochemical purity higher than 95% was obtained. The two complexes were hydrophilic, showed remarkable in vitro stability, good cellular uptake, binding affinity in the nanomolar range and high cellular internalization rate. Biodistribution studies revealed low blood uptake and elimination through the urinary tract. The addition of an acetyl group in the spacer increased the lipophilicity of C2 and modified the reactivity of the ε-amino group of the lysine which resulted in lower protein binding and lower percentage of injected dose in bladder and urine. The tumour versus muscle ratio was (3.8 ± 0.4) for 68 Ga-L1 and (4.7 ± 0.4) for 68 Ga-L2. These results encourage performing further studies in order to complete the evaluation of both tracers as potential radiopharmaceutical for breast cancer imaging.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Radioisótopos de Gálio/química , Neuropeptídeo Y/química , Compostos Radiofarmacêuticos/química , Aminas/química , Sequência de Aminoácidos , Animais , Transporte Biológico , Cinerradiografia , Feminino , Humanos , Lisina/química , Camundongos Nus , Neoplasias Experimentais , Neuropeptídeo Y/sangue , Neuropeptídeo Y/farmacocinética , Neuropeptídeo Y/urina , Ligação Proteica , Compostos Radiofarmacêuticos/sangue , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/urina , Coloração e Rotulagem , Relação Estrutura-Atividade , Distribuição Tecidual
4.
Waste Manag ; 126: 800-809, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33895563

RESUMO

Currently, in all developed countries there is great interest in improving democratic practices in local governments, as the administration closest to citizens. However, the possible influence of these actions on the management of public services and municipal finances have been side-lined, despite the great interest in evaluating the performance of local governments under budgetary constraints. Our research aims to fill this knowledge gap by studying the impact of key aspects of local governance (transparency and citizen participation), together with other environmental variables, on the efficiency of two municipal public services of both qualitative and quantitative importance: waste collection and street cleaning. The results show that the type of management, population density, the tourist activity of the municipality and the strength of local government are determinants that explain the efficiency of the public services examined in this research, while transparency and citizen participation have little impact.


Assuntos
Eliminação de Resíduos , Gerenciamento de Resíduos , Cidades , Governo Local , Densidade Demográfica
5.
Chem Biol Drug Des ; 95(2): 302-310, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31709766

RESUMO

The aim of this work was to develop and evaluate a 99m Tc-labeled neuropeptide Y derivative with affinity toward Y1-receptor. The selected amino acid sequence included nine amino acids derived from the C-terminal portion of the NPY complemented with the addition of one cysteine-mercaptoacetic acid moiety to bind the radiometal. Labeling was achieved through the preparation of a 3 + 1 nitrido complex. Physicochemical evaluation, cell uptake, internalization and externalization studies, and competitive assays were performed. Biodistribution experiments were carried out in normal and tumor-bearing mice. A single product with radiochemical purity >90% and high stability was obtained. In vitro analysis showed specific cellular uptake, IC50 of 73.2 nM, and a high internalization rate (80%). Biodistribution studies showed low blood and renal uptake and combined hepatobiliary and urinary elimination. Preliminary studies in mice bearing induced breast tumors rendered promising uptake values.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neuropeptídeo Y/administração & dosagem , Compostos Radiofarmacêuticos/administração & dosagem , Tecnécio/administração & dosagem , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual
6.
Miami; Alma Street; 2019. 325 p.
Monografia em Inglês | Sec. Est. Saúde SP, SESSP-ISPROD, Sec. Est. Saúde SP, SESSP-ISACERVO | ID: biblio-1006154
7.
Braz. j. infect. dis ; 21(5): 493-499, Sept.-Oct. 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-888910

RESUMO

Abstract Introduction Treatment of multidrug-resistant Gram-positive infections caused by Staphylococcus aureus remains as a clinical challenge due to emergence of new resistance mechanisms. Tedizolid is a next-generation oxazolidinone, recently approved for skin and soft tissues infections. We conducted a study to determine in vitro susceptibility to vancomycin, daptomycin, linezolid and tedizolid in MRSA clinical isolates from adult patients with skin and soft tissue infections. Material and methods Methicillin-resistant S. aureus isolates were collected in three tertiary-care hospitals of Medellin, Colombia, from February 2008 to June 2010 as part of a previous study. Clinical characteristics were assessed by medical records and MIC values were determined by Epsilometer test. Genotypic analysis included spa typing, MLST, and SCCmec typing. Results A total of 150 MRSA isolates were evaluated and tedizolid MIC values obtained showed higher in vitro activity than other antimicrobials, with MIC values ranging from 0.13 µg/mL to 0.75 µg/mL and lower values of MIC50 and MIC90 (0.38 µg/mL and 0.5 µg/mL). In contrast, vancomycin and linezolid had higher MIC values, which ranged from 0.5 µg/mL to 2.0 µg/mL and from 0.38 µg/mL to 4.0 µg/mL, respectively. Tedizolid MICs were 2- to 5-fold lower than those of linezolid. Clinical characteristics showed high previous antimicrobial use and hospitalization history. The majority of the strains belong to the CC8 harboring the SCCmec IVc and were associated with the spa t1610 (29.33%, n = 44). Conclusion In vitro effectiveness of tedizolid was superior for isolates from skin and soft tissue infections in comparison with the other antibiotics evaluated. The above added to its less toxicity, good bioavailability, daily dose and unnecessity of dosage adjustment, make tedizolid in a promising alternative for the treatment of infections caused by MRSA.


Assuntos
Humanos , Masculino , Feminino , Infecções Estafilocócicas/microbiologia , Infecções dos Tecidos Moles/microbiologia , Antibacterianos/farmacologia , Oxazóis/farmacologia , Organofosfatos/farmacologia , Vancomicina/farmacologia , Testes de Sensibilidade Microbiana , Daptomicina/farmacologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Linezolida/farmacologia
8.
Braz J Infect Dis ; 21(5): 493-499, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28432878

RESUMO

INTRODUCTION: Treatment of multidrug-resistant Gram-positive infections caused by Staphylococcus aureus remains as a clinical challenge due to emergence of new resistance mechanisms. Tedizolid is a next-generation oxazolidinone, recently approved for skin and soft tissues infections. We conducted a study to determine in vitro susceptibility to vancomycin, daptomycin, linezolid and tedizolid in MRSA clinical isolates from adult patients with skin and soft tissue infections. MATERIAL AND METHODS: Methicillin-resistant S. aureus isolates were collected in three tertiary-care hospitals of Medellin, Colombia, from February 2008 to June 2010 as part of a previous study. Clinical characteristics were assessed by medical records and MIC values were determined by Epsilometer test. Genotypic analysis included spa typing, MLST, and SCCmec typing. RESULTS: A total of 150 MRSA isolates were evaluated and tedizolid MIC values obtained showed higher in vitro activity than other antimicrobials, with MIC values ranging from 0.13µg/mL to 0.75µg/mL and lower values of MIC50 and MIC90 (0.38µg/mL and 0.5µg/mL). In contrast, vancomycin and linezolid had higher MIC values, which ranged from 0.5µg/mL to 2.0µg/mL and from 0.38µg/mL to 4.0µg/mL, respectively. Tedizolid MICs were 2- to 5-fold lower than those of linezolid. Clinical characteristics showed high previous antimicrobial use and hospitalization history. The majority of the strains belong to the CC8 harboring the SCCmec IVc and were associated with the spa t1610 (29.33%, n=44). CONCLUSION: In vitro effectiveness of tedizolid was superior for isolates from skin and soft tissue infections in comparison with the other antibiotics evaluated. The above added to its less toxicity, good bioavailability, daily dose and unnecessity of dosage adjustment, make tedizolid in a promising alternative for the treatment of infections caused by MRSA.


Assuntos
Antibacterianos/farmacologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções dos Tecidos Moles/microbiologia , Infecções Estafilocócicas/microbiologia , Daptomicina/farmacologia , Feminino , Humanos , Linezolida/farmacologia , Masculino , Testes de Sensibilidade Microbiana , Organofosfatos/farmacologia , Oxazóis/farmacologia , Vancomicina/farmacologia
9.
Rev. colomb. anestesiol ; 37(4): 356-372, nov.-ene. 2010. ilus, tab
Artigo em Inglês, Espanhol | LILACS | ID: lil-594611

RESUMO

El dolor neuropático es una patología cuya prevalencia requiere proponer guías de manejo. Su severidad y, en algunos casos, dificultad para el tratamiento deterioran la calidad de vida. La prevalencia reportada en Europa es del 5%, y en dolor crónico post-operatorio varía entre 5 y 85% dependiendo del tipo de cirugía. El objetivo del presente artículo es revisar las alternativas farmacológicas para el manejo de dolor neuropático de acuerdo con su fundamento fisiopatológico, y presentar sugerencias para el manejo con medicamentos disponibles en Colombia, incluidos y no incluidos en el Plan Obligatorio de Salud.


The prevalence of neuropathic pain requires proposals for management guidelines. In some cases, the degree of severity and the difficulty of treating this disorder has resulted in poor quality of life. In Europe, reported prevalence is 5%, and chronic postoperative pain ranges between 5% and 85%, depending on the type of surgery. The purpose of this paper is to review the pharmacological options for treating neuropathic pain depending on the pathophysiology, and suggest therapeutical approaches with medications available in Colombia, included or not in the Mandatory Health Plan.


Assuntos
Humanos , Masculino , Adolescente , Adulto , Feminino , Adulto Jovem , Pessoa de Meia-Idade , Neuralgia , Dor , Limiar da Dor , Terapêutica , Causalgia
10.
Ann Allergy Asthma Immunol ; 97(4): 457-63, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17069099

RESUMO

BACKGROUND: Clarithromycin is postulated to possess immunomodulatory properties in addition to its antimicrobial activity. OBJECTIVE: To evaluate the effect of clarithromycin on serum and nasopharyngeal cytokine and chemokine concentrations in children with an acute exacerbation of recurrent wheezing. METHODS: Children with a history of recurrent wheezing or asthma and who presented with an acute exacerbation of wheezing were enrolled in a double-blind, randomized trial of clarithromycin vs placebo. Concentrations of tumor necrosis factor alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-1beta (IL-1beta), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, RANTES, eotaxin, macrophage inflammatory protein 1alpha, macrophage inflammatory protein 1beta, and monocyte chemoattractant protein 1 were measured in serum and/or nasopharyngeal aspirates before, during, and after therapy. Mycoplasma pneumoniae and Chlamydophila pneumoniae infection were evaluated for by polymerase chain reaction and serologic testing. RESULTS: Nasopharyngeal concentrations of TNF-alpha, IL-1beta, and IL-10 were significantly and persistently lower in children treated with clarithromycin compared with placebo. There tended to be a greater effect of clarithromycin on nasopharyngeal cytokine concentrations in patients with evidence of M. pneumoniae or C. pneumoniae infection. No significant differences were detected in serum cytokines for children treated with clarithromycin compared with placebo. CONCLUSION: Clarithromycin therapy reduces mucosal TNF-alpha, IL-1beta, and IL-10 concentrations in children with an acute exacerbation of recurrent wheezing.


Assuntos
Asma/tratamento farmacológico , Quimiocinas/sangue , Claritromicina/uso terapêutico , Citocinas/sangue , Sons Respiratórios/efeitos dos fármacos , Doença Aguda , Adolescente , Asma/sangue , Asma/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Masculino , Placebos , Recidiva , Sons Respiratórios/imunologia
11.
Int J Antimicrob Agents ; 28(3): 253-8, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16891098

RESUMO

Mycoplasma pneumoniae infection has been associated with chronic lung disease. Treatment of chronic pulmonary mycoplasmosis has not been well investigated. BALB/c mice were intranasally inoculated once with M. pneumoniae or with sterile media (uninfected controls). Infected mice were treated with telithromycin or placebo daily for 10 days in the chronic phase of disease (18 months after inoculation). Mice (n=43) were evaluated before therapy and 1 day after completion of telithromycin. Treatment of infected mice with telithromycin at 18 months after infection significantly reduced chronic pulmonary histological inflammation compared with infected mice given placebo; however, this treatment did not improve airway obstruction or airway hyperresponsiveness. Therapy longer than 10 days may be necessary to improve pulmonary function.


Assuntos
Antibacterianos/uso terapêutico , Cetolídeos/uso terapêutico , Mycoplasma pneumoniae/efeitos dos fármacos , Pneumonia por Mycoplasma/tratamento farmacológico , Animais , Doença Crônica , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Pletismografia , Pneumonia por Mycoplasma/patologia , Pneumonia por Mycoplasma/fisiopatologia
12.
Antimicrob Agents Chemother ; 49(11): 4700-7, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16251314

RESUMO

Respiratory syncytial virus (RSV) is the leading viral pathogen responsible for bronchiolitis and pneumonia in infants and young children worldwide. We have previously shown in the mouse model that treatment with an anti-RSV neutralizing monoclonal antibody (MAb) against the F glycoprotein of RSV, palivizumab, decreased lung inflammation, airway obstruction, and postmethacholine airway hyperresponsiveness. MEDI-524, or Numax, is a new MAb derived from palivizumab with enhanced neutralizing activity against RSV. We compared the effects of these two MAbs on different markers of disease severity using the murine model of RSV infection. BALB/c mice were intranasally inoculated with RSV A2. Palivizumab or MEDI-524 was administered once at either 24 h before or 48 h after RSV inoculation. Regardless of the time of administration, all treated mice showed significantly decreased RSV loads in bronchoalveolar lavage samples measured by plaque assay. Only MEDI-524 given at -24 h significantly decreased lung RSV RNA loads on days 5 and 28 after RSV inoculation. Pulmonary histopathologic scores, airway obstruction, and postmethacholine airway hyperresponsiveness were significantly reduced in mice treated with MEDI-524 at 24 h before inoculation, compared with untreated controls and the other regimens evaluated. MEDI-524 was superior to palivizumab on several outcome variables of RSV disease assessed in the mouse model: viral replication, inflammatory and clinical markers of acute disease severity, and long-term pulmonary abnormalities.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antivirais/uso terapêutico , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Obstrução das Vias Respiratórias/prevenção & controle , Animais , Anticorpos Monoclonais Humanizados , Hiper-Reatividade Brônquica/prevenção & controle , Modelos Animais de Doenças , Feminino , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Palivizumab , Reação em Cadeia da Polimerase , Infecções por Vírus Respiratório Sincicial/complicações , Infecções por Vírus Respiratório Sincicial/patologia , Replicação Viral/efeitos dos fármacos
13.
Antimicrob Agents Chemother ; 49(9): 3970-3, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16127085

RESUMO

We evaluated the efficacy of azithromycin therapy given as a single high dose or divided over 5 days for the treatment of mild experimental Mycoplasma pneumoniae pneumonia. Although both azithromycin regimens significantly reduced quantitative cultures, lung histopathology, and pulmonary cytokines and chemokines, there were no significant differences between the two regimens.


Assuntos
Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Mycoplasma pneumoniae , Pneumonia por Mycoplasma/tratamento farmacológico , Animais , Antibacterianos/administração & dosagem , Azitromicina/administração & dosagem , Quimiocinas/metabolismo , Citocinas/metabolismo , Feminino , Pulmão/microbiologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Pneumonia por Mycoplasma/microbiologia , Pneumonia por Mycoplasma/patologia
14.
Antimicrob Agents Chemother ; 48(8): 2897-904, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15273098

RESUMO

Mycoplasma pneumoniae is a major etiologic agent of acute lower respiratory infections. We evaluated the antimicrobial and immunologic effects of cethromycin (ABT-773), a ketolide antibiotic, for the treatment of M. pneumoniae pneumonia in a mouse model. Eight-week-old BALB/c mice were inoculated intranasally once with 10(6) CFU of M. pneumoniae on day 0. Treatment was started 24 h after inoculation. Groups of mice were treated subcutaneously with cethromycin at 25 mg/kg of body weight or with placebo daily until sacrifice. Five to ten mice per group were evaluated at days 1, 4, 7, and 10 after inoculation. Outcome variables included bronchoalveolar lavage (BAL) for M. pneumoniae quantitative culture and cytokine and chemokine concentration determinations by enzyme-linked immunosorbent assay (tumor necrosis factor alpha [TNF-alpha], gamma interferon [IFN-gamma], interleukin-1beta [IL-1beta], IL-2, IL-4, IL-12, granulocyte-macrophage colony-stimulating factor, IL-8, monocyte chemoattractant protein 1 [MCP-1], and macrophage inflammatory protein 1alpha [MIP-1alpha]), histopathologic score of the lungs (HPS), and pulmonary function tests (PFT) using whole-body, unrestrained plethysmography at the baseline and post-methacholine exposure as indicators of airway obstruction (AO) and airway hyperresponsiveness (AHR), respectively. The cethromycin-treated mice had a greater reduction in M. pneumoniae culture titers than placebo-treated mice, reaching statistical significance on days 7 and 10 (P < 0.05). HPS was significantly reduced in cethromycin-treated mice compared with placebo-treated mice on days 4, 7, and 10 (P < 0.05). Cytokine concentrations in BAL samples were reduced in mice that received cethromycin, and the differences were statistically significant for 7 of the 10 cytokines measured (TNF-alpha, IFN-gamma, IL-1beta, IL-8, IL-12, MCP-1, and MIP-1alpha) on day 4 (P < 0.05). PFT values were improved in the cethromycin-treated mice, with AO and AHR significantly reduced on day 4 (P < 0.05). In this mouse model, treatment with cethromycin significantly reduced M. pneumoniae culture titers in BAL samples, cytokine and chemokine concentrations in BAL samples, histologic inflammation in the lungs, and disease severity as defined by AO and AHR.


Assuntos
Cefalosporinas/uso terapêutico , Eritromicina/uso terapêutico , Cetolídeos , Mycoplasma pneumoniae , Pneumonia por Mycoplasma/tratamento farmacológico , Mecânica Respiratória/fisiologia , Infecções Respiratórias/tratamento farmacológico , Obstrução das Vias Respiratórias/etiologia , Obstrução das Vias Respiratórias/fisiopatologia , Animais , Hiper-Reatividade Brônquica/etiologia , Hiper-Reatividade Brônquica/fisiopatologia , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Quimiocinas/metabolismo , Citocinas/biossíntese , Eritromicina/análogos & derivados , Pulmão/imunologia , Camundongos , Pletismografia , Pneumonia por Mycoplasma/imunologia , Pneumonia por Mycoplasma/patologia , Infecções Respiratórias/imunologia , Infecções Respiratórias/patologia
15.
Antimicrob Agents Chemother ; 48(5): 1811-22, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15105140

RESUMO

Numerous studies have described a strong association between respiratory syncytial virus (RSV) infection in infancy and the development of recurrent wheezing and airway hyperresponsiveness. We evaluated the effect of an anti-RSV neutralizing monoclonal antibody (palivizumab) on different aspects of RSV disease by using a murine model. BALB/c mice were intranasally inoculated with RSV A2. Palivizumab or an isotype-matched control antibody was administered once at 24 h before inoculation, 1 h after inoculation, or 48 h after inoculation. Regardless of the timing of administration, all mice treated with the neutralizing antibody showed significantly decreased RSV loads in bronchoalveolar lavage (BAL) and lung specimens compared with those of infected controls. Pulmonary histopathologic scores, airway obstruction measured by plethysmography, and airway hyperresponsiveness after methacholine challenge were significantly reduced in mice treated with the anti-RSV antibody 24 h before inoculation compared with those for untreated controls. Concentrations of interferon-gamma, interleukin-10, macrophage inflammatory protein 1alpha, regulated on activation normal T-cell expressed and secreted (RANTES), and eotaxin in BAL fluids were also significantly reduced in mice treated with palivizumab 24 h before inoculation. This study demonstrates that reduced RSV replication was associated with significant modulation of inflammatory and clinical markers of acute disease severity and significant improvement of the long-term pulmonary abnormalities. Studies to determine whether strategies aimed at preventing or reducing RSV replication could decrease the long-term morbidity associated with RSV infection in children should be considered.


Assuntos
Obstrução das Vias Respiratórias/terapia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Antivirais/uso terapêutico , Antivirais/uso terapêutico , Hiper-Reatividade Brônquica/terapia , Pulmão/patologia , Pneumonia/tratamento farmacológico , Pneumonia/patologia , Infecções por Vírus Respiratório Sincicial/terapia , Obstrução das Vias Respiratórias/etiologia , Animais , Anticorpos Monoclonais Humanizados , Hiper-Reatividade Brônquica/etiologia , Líquido da Lavagem Broncoalveolar/química , Linhagem Celular , Quimiocinas/metabolismo , Citocinas/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Palivizumab , Pletismografia Total , Testes de Função Respiratória , Infecções por Vírus Respiratório Sincicial/complicações , Infecções por Vírus Respiratório Sincicial/patologia , Fixação de Tecidos
16.
Antimicrob Agents Chemother ; 47(5): 1614-20, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12709330

RESUMO

Because macrolide antibiotics are hypothesized to possess immunomodulatory activity independent of their antimicrobial activity, we evaluated the immunomodulatory effect of clarithromycin in a murine model of lung inflammation induced by either live or UV-killed Mycoplasma pneumoniae. BALB/c mice were intranasally inoculated once with live or UV-killed M. pneumoniae. Clarithromycin (25 mg/kg of body weight) or placebo was subcutaneously administered once daily in both groups of mice. In mice infected with live M. pneumoniae, clarithromycin treatment significantly reduced quantitative M. pneumoniae bronchoalveolar lavage (BAL) culture, pulmonary histopathologic scores (HPS), and airway resistance-obstruction (as measured by plethysmography) compared with placebo. Concentrations of tumor necrosis factor alpha, gamma interferon, interleukin-6 (IL-6), mouse KC (functional IL-8), JE/MCP-1, and MIP-1alpha in BAL fluid were also significantly decreased in mice infected with live M. pneumoniae given clarithromycin. In contrast, mice inoculated with UV-killed M. pneumoniae had no significant reduction in HPS, airway resistance-obstruction, or BAL cytokine or chemokine concentrations in response to clarithromycin administration. Clarithromycin therapy demonstrated beneficial effects (microbiologic, histologic, respiratory, and immunologic) on pneumonia in the mice infected with live M. pneumoniae; this was not observed in the mice inoculated with UV-killed M. pneumoniae.


Assuntos
Claritromicina/uso terapêutico , Pneumonia por Mycoplasma/tratamento farmacológico , Animais , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/microbiologia , Quimiocinas/análise , Claritromicina/farmacologia , Citocinas/análise , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Pletismografia , Pneumonia por Mycoplasma/imunologia , Pneumonia por Mycoplasma/patologia
17.
Artigo em Espanhol | PAHO | ID: pah-27333

RESUMO

Las enfermedades invasoras ocasionadas por Streptococcus pneumoniae han sido por mucho tiempo una causa importante de mortalidad. Si bien se sabe que la resistencia de S. pneumoniae a la penicilina y otros antimicrobianos se ha incrementado con el tiempo, aún no se ha esclarecido el efecto de este cambio sobre la mortalidad. Se desconoce igualmente el impacto de la virulencia de los tipos capsulares del microorganismo en la mortalidad. El objetivo de este estudio de cohorte retrospectivo fue determinar los factores de riesgo de mortalidad por enfermedad neumocócica en niños menores de 5 años. Durante un estudio de srotipificación de S. penumoniae patrocinado por el Sistema Regional de Vacunas de la OPS se revisaron con este fin las fichas epidemiológicas de 245 pacientes de esa edad en quienes se diagnosticó enfermedad invasora por S. pneumoniae entre 1994 y 1996 en Colombia. De los 245 pacientes, 29 (11 por cien) fallecieron. En el análisis univariado no se establecieron diferencias significativas entre los pacientes que murieron y aquellos que sobrevivieron en cuanto a edad, sexo, procesos patológicos subyacentes al ingresar, o concordancia del tratamiento antimicrobiano recibido. Las variables que se asociaron con la mortalidad fueron un diagnóstico de meningitis; infección por S. pneumoniae resistente a la penicilina, trimetoprima-sulfametoxazol (TMS) o eritromicina; multirresistencia y los tipos capsulares, 6,23F, 7F, 8 y 35 B. En el análisis por regresión logística siguieron mostrando asociación con la mortalidad los tipos capsulares 7F (razón de posibilidades u odds ratio [OR])=7,13; (P= 0,04) y 8(OR= 13,8; P= 0,07), la polipnea (OR= 2,74; P= 0,03), el diagnóstico de meningitis (OR= 5,02; P= 0,0001) y la resistencia a TMS (OR= 2,62; P= 0,02). En los casos de neumonía, el factor que más se asoció con la mortalidad fue el tipo capsular, mientras que en los casos de meningitis, dicho factor fue la resistencia a antimicrobianos. En el desarrollo de una vacuna deberían tenerse en cuenta las diferencias de mortalidad según los serotipos, a fin de lograr un mayor impacto en la morbilidad y mortalidad infantiles por enfermedad de origne neumocócico


Assuntos
Resistência Microbiana a Medicamentos , Streptococcus pneumoniae , Mortalidade Infantil/tendências , Meningite Pneumocócica , América Latina
18.
Rev. panam. salud pública ; 5(2): 69-76, feb. 1999. tab
Artigo em Espanhol | LILACS | ID: lil-231334

RESUMO

Las enfermedades invasoras ocasionadas por Streptococcus pneumoniae han sido por mucho tiempo una causa importante de mortalidad. Si bien se sabe que la resistencia de S. pneumoniae a la penicilina y otros antimicrobianos se ha incrementado con el tiempo, aún no se ha esclarecido el efecto de este cambio sobre la mortalidad. Se desconoce igualmente el impacto de la virulencia de los tipos capsulares del microorganismo en la mortalidad. El objetivo de este estudio de cohorte retrospectivo fue determinar los factores de riesgo de mortalidad por enfermedad neumocócica en niños menores de 5 años. Durante un estudio de srotipificación de S. penumoniae patrocinado por el Sistema Regional de Vacunas de la OPS se revisaron con este fin las fichas epidemiológicas de 245 pacientes de esa edad en quienes se diagnosticó enfermedad invasora por S. pneumoniae entre 1994 y 1996 en Colombia. De los 245 pacientes, 29 (11 por cien) fallecieron. En el análisis univariado no se establecieron diferencias significativas entre los pacientes que murieron y aquellos que sobrevivieron en cuanto a edad, sexo, procesos patológicos subyacentes al ingresar, o concordancia del tratamiento antimicrobiano recibido. Las variables que se asociaron con la mortalidad fueron un diagnóstico de meningitis; infección por S. pneumoniae resistente a la penicilina, trimetoprima-sulfametoxazol (TMS) o eritromicina; multirresistencia y los tipos capsulares, 6,23F, 7F, 8 y 35 B. En el análisis por regresión logística siguieron mostrando asociación con la mortalidad los tipos capsulares 7F (razón de posibilidades u odds ratio [OR])=7,13; (P= 0,04) y 8(OR= 13,8; P= 0,07), la polipnea (OR= 2,74; P= 0,03), el diagnóstico de meningitis (OR= 5,02; P= 0,0001) y la resistencia a TMS (OR= 2,62; P= 0,02). En los casos de neumonía, el factor que más se asoció con la mortalidad fue el tipo capsular, mientras que en los casos de meningitis, dicho factor fue la resistencia a antimicrobianos. En el desarrollo de una vacuna deberían tenerse en cuenta las diferencias de mortalidad según los serotipos, a fin de lograr un mayor impacto en la morbilidad y mortalidad infantiles por enfermedad de origne neumocócico


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Streptococcus pneumoniae , Resistência Microbiana a Medicamentos , Mortalidade Infantil/tendências , Meningite Pneumocócica , América Latina
20.
Artigo em Espanhol | PAHO | ID: pah-8334

RESUMO

Este artículo resume la experiencia del desarrollo de los sistemas locales de salud (SILOS) en el Uruguay y los elementos favorecedores del conocimiento y difusión de este concepto. A partir de 1988, el Ministerio de Salud Pública asumió la responsabilidad de ser una de las entidades encargadas del fortalecimiento de los SILOS en el país. Con este criterio se creó un grupo técnico para actuar a nivel central, proponiendo y promoviendo cambios orientados a desconcentrar la utilización de recursos de acuerdo cpn orientaciones generales y a nivel local, actuando como elemento catalizador de la gestión de la prestación de servicios de salud entendida como concepto sistématico


Assuntos
Sistemas Locais de Saúde/tendências , Política , Uruguai
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