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1.
Tissue Eng Regen Med ; 21(2): 223-242, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37856070

RESUMO

BACKGROUND: Poly (lactic acid) (PLA) is a biodegradable polyester that has been exploited for a variety of biomedical applications, including tissue engineering. The incorporation of ß-tricalcium phosphate (TCP) into PLA has imparted bioactivity to the polymeric matrix. METHODS: We have modified a 90%PLA-10%TCP composite with SiO2 and MgO (1, 5 and 10 wt%), separately, to further enhance the material bioactivity. Filaments were prepared by extrusion, and scaffolds were fabricated using 3D printing technology associated with fused filament fabrication. RESULTS: The PLA-TCP-SiO2 composites presented similar structural, thermal, and rheological properties to control PLA and PLA-TCP. In contrast, the PLA-TCP-MgO composites displayed absence of crystallinity, lower polymeric molecular weight, accelerated degradation ratio, and decreased viscosity within the 3D printing shear rate range. SiO2 and MgO particles were homogeneously dispersed within the PLA and their incorporation increased the roughness and protein adsorption of the scaffold, compared to a PLA-TCP scaffold. This favorable surface modification promoted cell proliferation, suggesting that SiO2 and MgO may have potential for enhancing the bio-integration of scaffolds in tissue engineering applications. However, high loads of MgO accelerated the polymeric degradation, leading to an acid environment that imparted the composite biocompatibility. The presence of SiO2 stimulated mesenchymal stem cells differentiation towards osteoblast; enhancing extracellular matrix mineralization, alkaline phosphatase (ALP) activity, and bone-related genes expression. CONCLUSION: The PLA-10%TCP-10%SiO2 composite presented the most promising results, especially for bone tissue regeneration, due to its intense osteogenic behavior. PLA-10%TCP-10%SiO2 could be used as an alternative implant for bone tissue engineering application.


Assuntos
Fosfatos de Cálcio , Óxido de Magnésio , Alicerces Teciduais , Óxido de Magnésio/farmacologia , Óxido de Magnésio/química , Alicerces Teciduais/química , Dióxido de Silício , Teste de Materiais , Poliésteres , Polímeros/química , Ácido Láctico/química , Impressão Tridimensional
2.
Biomater Biosyst ; 13: 100086, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38213985

RESUMO

The fabrication of customized implants by additive manufacturing has allowed continued development of the personalized medicine field. Herein, a 3D-printed bioabsorbable poly (lactic acid) (PLA)- ß-tricalcium phosphate (TCP) (10 wt %) composite has been modified with CeO2 nanoparticles (CeNPs) (1, 5 and 10 wt %) for bone repair. The filaments were prepared by melt extrusion and used to print porous scaffolds. The nanocomposite scaffolds possessed precise structure with fine print resolution, a homogenous distribution of TCP and CeNP components, and mechanical properties appropriate for bone tissue engineering applications. Cell proliferation assays using osteoblast cultures confirmed the cytocompatibility of the composites. In addition, the presence of CeNPs enhanced the proliferation and differentiation of mesenchymal stem cells; thereby, increasing alkaline phosphatase (ALP) activity, calcium deposition and bone-related gene expression. Results from this study have shown that the 3D printed PLA-TCP-10%CeO2 composite scaffold could be used as an alternative polymeric implant for bone tissue engineering applications: avoiding additional/revision surgeries and accelerating the regenerative process.

3.
Natl J Maxillofac Surg ; 14(2): 326-329, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37661981

RESUMO

Late reconstructions of gunshot wounds (GSWs) in the orbital area are a true challenge to the oral and maxillofacial surgeon. Usually, the wall defects are large in size and commonly present loss of orbital volume, which can cause ocular dystopia. The only exceptions are when there is an explosion of the orbital walls-that is, blow-out fractures. We encountered a patient with a two-year sequelae after GSW in the face that caused the destructed orbit to have a 2.5 bigger size than the contralateral orbit, requiring meticulous planning of a patient-specific implant (PSI) to correctly reconstruct the orbit volume and bone projection. The PSI was developed using titanium and it had three pieces that could reconstruct all four walls of the orbit. After surgery, the patient regained orbital volume and malar projection, allowing him to benefit from facial symmetry. The PSI can be used to reconstruct all the orbital walls in cases of complex bone defects.

4.
Natl J Maxillofac Surg ; 14(3): 515-518, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38273912

RESUMO

Hemifacial microsomia (HFM) is a complex congenital malformation with an extremely variable phenotypic presentation. It usually involves structures of the first and second pharyngeal arches. Anomalies of the cardiac, pulmonary, renal, and gastrointestinal systems are present, but the main characteristic is the mandibular hypoplasia. This is commonly treated with orthodontic hardware and various surgical modalities. Most recently, a total joint replacement with a customized prosthesis is idealized to provide the best outcomes to these patients, so it has been used in some cases. The following case is of a 23-year-old female with congenital hypoplastic mandibular head and the absence of mandibular fossa. The proposed treatment was to reconstruct the mandible with a customized prosthesis and orthognathic surgery to correct the asymmetry and provide better phonation, speech, and facial contour. The patient is under six years follow-up with a complete adaptation of the prosthesis.

5.
J Pediatr ; 161(6): 1104-8, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22748516

RESUMO

OBJECTIVE: To test the hypothesis that azithromycin reduces the length of hospitalization and oxygen requirement in infants with acute viral bronchiolitis (AB). STUDY DESIGN: We performed a randomized, double-blinded, placebo-controlled trial in southern Brazil, from 2009 to 2011. Infants (<12 months of age) hospitalized with AB were recruited in 2 hospitals. Patients were randomized to receive either azithromycin or placebo, administered orally, for 7 days. At enrollment, clinical data were recorded and nasopharyngeal samples were collected for viral identification through immunofluorescence. Main outcomes were duration of oxygen requirement and length of hospitalization. RESULTS: One hundred eighty-four patients were included in the study (azithromycin 88 subjects, placebo 96 subjects). Baseline clinical characteristics and viral identification were not different between the groups studied. A virus was detected in 112 (63%) patients, and of those, 92% were positive for respiratory syncytial virus. The use of azithromycin did not reduce the median number of days of either hospitalization (P = .28) or oxygen requirement (P = .47). CONCLUSIONS: Azithromycin did not improve major clinical outcomes in a large sample of hospitalized infants with AB, even when restricting the findings to those with positive respiratory syncytial virus samples. Azithromycin therapy should not be given for AB because it provides no benefit and overuse increases overall antibiotic resistance.


Assuntos
Anti-Inflamatórios/uso terapêutico , Azitromicina/uso terapêutico , Bronquiolite Viral/tratamento farmacológico , Influenza Humana/tratamento farmacológico , Infecções por Paramyxoviridae/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Doença Aguda , Administração Oral , Bronquiolite Viral/diagnóstico , Bronquiolite Viral/terapia , Terapia Combinada , Método Duplo-Cego , Esquema de Medicação , Feminino , Hospitalização , Humanos , Lactente , Recém-Nascido , Influenza Humana/diagnóstico , Influenza Humana/terapia , Estimativa de Kaplan-Meier , Tempo de Internação/estatística & dados numéricos , Masculino , Oxigenoterapia , Infecções por Paramyxoviridae/diagnóstico , Infecções por Paramyxoviridae/terapia , Infecções por Vírus Respiratório Sincicial/diagnóstico , Infecções por Vírus Respiratório Sincicial/terapia , Resultado do Tratamento
6.
Materials (Basel) ; 15(6)2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35329574

RESUMO

Once administered in an organism, the physiological parameters of magnetic nanoparticles (MNPs) must be addressed, as well as their possible interactions and retention and elimination profiles. Alternating current biosusceptometry (ACB) is a biomagnetic detection system used to detect and quantify MNPs. The aims of this study were to evaluate the biodistribution and clearance of MNPs profiles through long-time in vivo analysis and determine the elimination time carried out by the association between the ACB system and MnFe2O4 nanoparticles. The liver, lung, spleen, kidneys, and heart and a blood sample were collected for biodistribution analysis and, for elimination analysis, and over 60 days. During the period analyzed, the animal's feces were also collectedd. It was possible to notice a higher uptake by the liver and the spleen due to their characteristics of retention and uptake. In 60 days, we observed an absence of MNPs in the spleen and a significant decay in the liver. We also determined the MNPs' half-life through the liver and the spleen elimination. The data indicated a concentration decay profile over the 60 days, which suggests that, in addition to elimination via feces, there is an endogenous mechanism of metabolization or possible agglomeration of MNPs, resulting in loss of ACB signal intensity.

7.
Aging (Albany NY) ; 13(2): 1686-1691, 2021 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-33471779

RESUMO

Severe therapy-resistant asthma (STRA) is closely associated with distinct clinical and inflammatory pheno-endotypes, which may contribute to the development of age-related comorbidities. Evidence has demonstrated a contribution of accelerated telomere shortening on the poor prognosis of respiratory diseases in adults. Eotaxin-1 (CCL11) is an important chemokine for eosinophilic recruitment and the progression of asthma. In the last years has also been proposed as an age-promoting factor. This study aimed to investigate the association of relative telomere length (rTL) and eotaxin-1 in asthmatic children. Children aged 8-14 years (n=267) were classified as healthy control (HC, n=126), mild asthma (MA, n=124) or severe therapy-resistant asthma (STRA, n=17). rTL was performed by qPCR from peripheral blood. Eotaxin-1 was quantified by ELISA from fresh-frozen plasma. STRA had shorter telomeres compared to HC (p=0.02) and MA (p=0.006). Eotaxin-1 levels were up-regulated in STRA [median; IQR25-75)] [(1,190 pg/mL; 108-2,510)] compared to MA [(638 pg/mL; 134-1,460)] (p=0.03) or HC [(627 pg/mL; 108-1,750)] (p<0.01). Additionally, shorter telomeres were inversely correlated with eotaxin-1 levels in STRA (r=-0.6, p=0.013). Our results suggest that short telomeres and up-regulated eotaxin-1, features of accelerated aging, could prematurely contribute to a senescent phenotype increasing the risk for early development of age-related diseases in asthma.


Assuntos
Envelhecimento/genética , Asma/genética , Encurtamento do Telômero/fisiologia , Adolescente , Envelhecimento/sangue , Asma/sangue , Estudos de Casos e Controles , Quimiocina CCL11/sangue , Criança , Feminino , Humanos , Masculino
8.
Pharmaceutics ; 13(8)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34452233

RESUMO

Pharmacomagnetography involves the simultaneous assessment of solid dosage forms (SDFs) in the human gastrointestinal (GI) tract and the drug plasmatic concentration, using a biomagnetic technique and pharmacokinetics analysis. This multi-instrumental approach helps the evaluation, as GI variables can interfere with the drug delivery processes. This study aimed to employ pharmacomagnetography to evaluate the influence of omeprazole on the drug release and absorption of metronidazole administered orally in magnetic-coated tablets. Magnetic-coated tablets, coated with Eudragit® E-100 (E100) and containing 100 mg of metronidazole, were produced. For the in vivo experiments, 12 volunteers participated in the two phases of the study (placebo and omeprazole) on different days to assess the bioavailability of metronidazole. The results indicated a shift as the pH of the solution increased and a delay in the dissolution of metronidazole, showing that the pH increase interferes with the release processes of tablets coated with E100. Our study reinforced the advantages of pharmacomagnetography as a tool to perform a multi-instrumental correlation analysis of the disintegration process and the bioavailability of drugs.

9.
Respir Res ; 11: 23, 2010 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-20181264

RESUMO

BACKGROUND: Atopic and non-atopic wheezing may be caused by different etiologies: while eosinophils are more important in atopic asthmatic wheezers, neutrophils are predominantly found in BAL samples of young children with wheezing. Both neutrophils as well as eosinophils may secrete matrix metalloproteinase 9 (MMP-9). Considering that MMP-9 plays an important role in airway wall thickening and airway inflammation, it may influence the development of obstructive airway phenotypes in children. In the present study we investigated whether genetic variations in MMP-9 influence the development of different forms of childhood asthma. METHODS: Genotyping of four HapMap derived tagging SNPs in the MMP-9 gene was performed using MALDI-TOF MS in three cross sectional study populations of German children (age 9-11; N = 4,264) phenotyped for asthma and atopic diseases according to ISAAC standard procedures. Effects of single SNPs and haplotypes were studied using SAS 9.1.3 and Haploview. RESULTS: SNP rs2664538 significantly increased the risk for non-atopic wheezing (OR 2.12, 95%CI 1.40-3.21, p < 0.001) and non-atopic asthma (OR 1.66, 95%CI 1.12-2.46, p = 0.011). Furthermore, the minor allele of rs3918241 may be associated with decreased expiratory flow measurements in non-atopic children. No significant effects on the development of atopy or total serum IgE levels were observed. CONCLUSIONS: Our results have shown that homozygocity for MMP-9 variants increase the risk to develop non-atopic forms of asthma and wheezing, which may be explained by a functional role of MMP-9 in airway remodeling. These results suggest that different wheezing disorders in childhood are affected differently by genetic alterations.


Assuntos
Asma/epidemiologia , Asma/genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Metaloproteinase 9 da Matriz/genética , Polimorfismo de Nucleotídeo Único/genética , Criança , Feminino , Variação Genética/genética , Alemanha/epidemiologia , Humanos , Hipersensibilidade Imediata/epidemiologia , Hipersensibilidade Imediata/genética , Incidência , Masculino , Mutação , Medição de Risco/métodos , Fatores de Risco
10.
J Allergy Clin Immunol ; 123(1): 82-88.e6, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19038437

RESUMO

BACKGROUND: Major transcription factors controlling T(H)1 and T(H)2 development, such as T-box transcription factor and GATA3, might be centrally involved in asthma and atopic diseases. Only recently, the homeobox transcription factor H.20-like homeobox 1 (HLX1), interacting closely with T-box transcription factor, has been identified as an important regulator of T(H)1 differentiation and suppressor of T(H)2 commitment. OBJECTIVE: We investigated whether genetic variations in the HLX1 gene exist and whether these could affect the development of childhood asthma. METHODS: The HLX1 gene was resequenced in 80 chromosomes. Associations between identified polymorphisms, asthma, and atopic diseases were investigated in German children (total n = 3099) from the cross-sectional International Study of Asthma and Allergy in Childhood phase II. Functional properties of polymorphisms were studied by using luciferase reporter gene assays and electrophoretic mobility shift assays in T cells. All statistical analyses were performed with SAS/Genetics software (SAS Institute, Inc, Cary, NC). RESULTS: Nineteen polymorphisms were identified in the HLX1 gene, and 2 tagging single nucleotide polymorphisms representing 7 polymorphisms were associated with childhood asthma in our study population. Two promoter polymorphisms, C-1407T and C-742G, contained in 1 tagging block were associated with asthma (odds ratio, 1.44; 95% CI, 1.11-1.86; P = .0061), significantly decrease promoter transactivation, and disrupt specificity protein-transcription factor binding in in vitro experiments. CONCLUSIONS: Our data suggest that polymorphisms in the HLX1 gene increase the risk for childhood asthma. On the cellular level, altered binding of specificity protein-transcription factors to the HLX1 promoter and subsequent changes in HLX1 gene expression might contribute to these effects.


Assuntos
Asma/genética , Proteínas de Homeodomínio/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Fatores de Transcrição/genética , Asma/imunologia , Asma/metabolismo , Criança , Estudos Transversais , Feminino , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/imunologia , Fator de Transcrição GATA3/metabolismo , Proteínas de Homeodomínio/imunologia , Proteínas de Homeodomínio/metabolismo , Humanos , Masculino , Regiões Promotoras Genéticas/imunologia , Fatores de Risco , Células Th1/imunologia , Células Th1/metabolismo , Células Th2/imunologia , Células Th2/metabolismo , Fatores de Transcrição/imunologia , Fatores de Transcrição/metabolismo
11.
J Allergy Clin Immunol ; 123(5): 1062-8, 1068.e1-8, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19362357

RESUMO

BACKGROUND: The T cell-specific T-box transcription factor (TBX21) plays a crucial role in the regulation of the immune system because this factor induces the differentiation of T(H)1 and blocks T(H)2 commitment together with the homeobox transcription factor HLX1. OBJECTIVE: The role of genetic variants in TBX21 alone and in combination with HLX1 polymorphisms was investigated in the development of T(H)2-associated atopy and asthma. METHODS: The TBX21 gene was resequenced in 37 adult volunteers. Polymorphisms identified were genotyped in a cross-sectional (N = 3099) and nested asthma case-control population (N = 1872) using mainly matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Effects of promoter polymorphisms on TBX21 gene expression were studied by reporter gene assays. Furthermore, the impact of combinations of TBX21 and HLX1 polymorphisms on the development of asthma was assessed by using a risk score model. Statistical analyses were performed by using SAS/Genetics. RESULTS: Forty-three polymorphisms were identified in the TBX21 gene. Considering a minor allele frequency of at least 10%, single nucleotide polymorphisms were assigned to 7 linkage disequilibrium blocks. Three tagging single nucleotide polymorphisms increased childhood asthma risk significantly (odds ratio [OR], 2.60, 95% CI, 1.34-5.03, P = .003; OR, 1.39, 95% CI, 1.02-1.90, P = .039; and OR, 1.97, 95% CI, 1.18-3.30, P = .009). TBX21 promoter polymorphisms contained in 2 blocks significantly influenced TBX21 promoter activity. In a risk score model, the combination of TBX21 and HLX1 polymorphisms increased the asthma risk by more than 3-fold. CONCLUSIONS: These data suggest that TBX21 polymorphisms contribute to the development of asthma, potentially by altering TBX21 promoter activity. A risk score model indicates that TBX21 and HLX1 polymorphisms may have synergistic effects on asthma risk.


Assuntos
Asma/genética , Frequência do Gene/genética , Proteínas de Homeodomínio/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas com Domínio T/genética , Fatores de Transcrição/genética , Alelos , Asma/epidemiologia , Asma/imunologia , Estudos de Casos e Controles , Criança , Estudos Transversais , Predisposição Genética para Doença , Genótipo , Alemanha/epidemiologia , Humanos , Desequilíbrio de Ligação/genética , Prevalência , Regiões Promotoras Genéticas
12.
PLoS One ; 15(1): e0228022, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31990945

RESUMO

INTRODUCTION: Pertussis is an important public health problem worldwide, especially in infants. An increase in the incidence in many countries occurred after 2010, including Brazil. In 2013, dTpa vaccine was introduced in the Brazil national immunization schedule of pregnant women. The objective of this study was to evaluate the national trends in the incidence of pertussis in Brazil in children under 1 year old, and the impact of the introduction of dTpa vaccine during pregnancy. METHODS: The incidence of hospitalizations and non-hospitalized confirmed cases of pertussis in neonates (< 1 month age) and young infants (1 month-< 1 year age) were analyzed, comparing the incidence in pre maternal vaccination (2011-2013) with the post-vaccination (2015-2017). We used non-respiratory hospitalizations as comparison, during the same period. A database of the Brazilian Ministry of Health (DATASUS) was used to analyze cases from 2007 to 2017 and the subsets of 2011-2013 and 2015-2017, after Pertussis resurgence. The vaccination data was accessed through the link of the Information System of the National Immunization Program (pni.datasus.gov.br). RESULTS: Between 2007 and 2017, 17,818 children under one year of age were hospitalized due to pertussis in Brazil. In the pre maternal vaccination period 2011-2013, the mean annual incidence of non-hospitalized confirmed cases of pertussis in children under 1 month was 722.2 / 100,000 and in the period of 2015-2017 the average was 377.3 / 100,000, representing a decrease of 47.7% [IRR 0.52 (0.46-0.59)]. At those periods of time, the average incidence per year for children of one month-< 1 year aged was 64.9 / 100,000 (2011-2013) and 29.3 / 100,000 (2015-2017) [IRR 0.45 (CI 0.29-0.69)]. CONCLUSION: Vaccination of pregnant woman coincides with the reduction in the number of cases of pertussis in children under 1 month of age from 2015. Immunization of pregnant woman seems to have an important impact on the prevention of the disease in young infants who have not yet received their own pertussis vaccine.


Assuntos
Hospitalização/estatística & dados numéricos , Programas de Imunização/organização & administração , Vacina contra Coqueluche/administração & dosagem , Vacinação/métodos , Coqueluche/prevenção & controle , Adulto , Bordetella pertussis/efeitos dos fármacos , Bordetella pertussis/imunologia , Brasil/epidemiologia , Criança , Bases de Dados Factuais , Feminino , Humanos , Esquemas de Imunização , Incidência , Lactente , Recém-Nascido , Masculino , Gravidez , Gestantes , Coqueluche/epidemiologia , Coqueluche/imunologia
13.
Nanomedicine (Lond) ; 15(5): 511-525, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32077357

RESUMO

Aim: This paper aims to investigate a doxorubicin (DOX) chronic kidney disease rat model using magnetic nanoparticles (MNPs) associated with the alternate current biosusceptometry (ACB) to analyze its different perfusion profiles in both healthy and DOX-injured kidneys. Materials & methods: We used the ACB to detect the MNP kidney perfusion in vivo. Furthermore, we performed biochemical and histological analyses, which sustained results obtained from the ACB system. We also studied the MNP biodistribution. Results: We found that DOX kidney injury alters the MNPs' kidney perfusion. These changes became more intense as the disease progressed. Moreover, DOX has an important effect on MNP biodistribution as the disease evolved. Conclusion: This study provides new applications of MNPs in nephrology, instrumentation, pharmacology, physiology and nanomedicine.


Assuntos
Doxorrubicina/efeitos adversos , Rim/efeitos dos fármacos , Nanopartículas de Magnetita , Animais , Rim/fisiopatologia , Ratos , Distribuição Tecidual
14.
Mol Diagn Ther ; 24(3): 315-325, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32185651

RESUMO

INTRODUCTION: The incorporation of molecular genetic testing into cystic fibrosis (CF) screening programs increases the specificity of the diagnostic strategy and has the potential to decrease the rate of false- positive results. In this sense, our objective was to develop a genotyping assay that could detect 25 pathogenic variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene with high sensitivity and that could be incorporated into the routine of newborn screening, complementing the current existing protocol used in our public health institution. METHODS: A mini-sequencing assay was standardized using single-base extension in a previously genotyped control sample. This strategy was validated in a Brazilian cohort of CF patients by Sanger sequencing. RESULTS: The inclusion of the 25 variants in the current newborn screening program increased the identification rates of two alleles from 33 to 52.43% in CF patients. This new approach was able to detect a total of 37 variants, which represents 93.01% of all mutated alleles described in the last CF Brazilian Register. CONCLUSIONS: Mini-sequencing for the simultaneous detection of 25 CFTR gene variants improves the screening of Brazilian newborns and decreases the number of inconclusive cases. This method uses minimal hands-on time and is suited for rapid screening, which reduces sample processing costs.


Assuntos
Alelos , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/diagnóstico , Fibrose Cística/genética , Testes Genéticos , Mutação , Triagem Neonatal , Substituição de Aminoácidos , Brasil/epidemiologia , Fibrose Cística/epidemiologia , Testes Genéticos/métodos , Genótipo , Humanos , Recém-Nascido , Reação em Cadeia da Polimerase Multiplex , Análise de Sequência de DNA
15.
Am J Respir Crit Care Med ; 177(6): 613-21, 2008 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-18079498

RESUMO

RATIONALE: The development of atopic diseases is characterized by skewed immune responses to common allergens. Only recently, interferons have been identified to play a crucial role in these mechanisms. OBJECTIVES: Because interferon regulatory factor (IRF)-1 is critical for interferon expression, we tested the hypotheses that genetic changes in this essential transcription factor may have consequences for the development of atopy. METHODS: The IRF-1 gene locus was resequenced in 80 human chromosomes. Association and haplotype analyses were performed in a cross-sectional study population of German children from Dresden (n = 1,940), and results were replicated in a second population sample from Munich (n = 1,159), both part of the ISAAC (International Study of Asthma and Allergy in Childhood) phase II. Promoter polymorphism effects were studied using electrophoretic mobility shift assay and colorimetric binding assays. Allele-specific IRF-1 gene expression was studied in vitro using luciferase reporter assays, whereas we assessed ex vivo expression of IRF-1 by real-time polymerase chain reaction and IFN-gamma protein by Luminex technology (Bio-Rad, Hercules, CA). Statistical analyses were performed using SAS/Genetics (SAS 9.1.3; SAS Institute, Cary, NC). MEASUREMENTS AND MAIN RESULTS: By resequencing, 49 polymorphisms were identified within the IRF-1 gene. Four blocks containing 11 polymorphisms were significantly associated with atopy, total IgE levels, or specific IgE levels in both populations (P < 0.05). Two polymorphisms changed transcription factor binding of nuclear factor (NF)-kappaB and EGR1 (early growth response 1) to the IRF-1 promoter, altered gene expression in vitro (P = 0.0004), and altered IRF-1 mRNA and IFN-gamma protein expression ex vivo. CONCLUSIONS: Our results suggest that functionally relevant IRF-1 polymorphisms influence atopy risk, potentially by altering transcription factor binding, IRF-1 gene expression, and IFN-gamma regulation.


Assuntos
Hipersensibilidade/genética , Imunoglobulina E , Fator Regulador 1 de Interferon/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Estudos de Casos e Controles , Criança , Estudos Transversais , Predisposição Genética para Doença , Genótipo , Alemanha , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Testes Cutâneos
16.
IEEE Trans Nanobioscience ; 18(3): 456-462, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30998477

RESUMO

In this paper, the application of a technique to evaluate in vivo biodistribution of magnetic nanoparticles (MNP) is addressed: the Multichannel AC Biosusceptometry System (MC-ACB). It allows real-time assessment of magnetic nanoparticles in both bloodstream clearance and liver accumulation, where a complex network of inter-related cells is responsible for MNP uptake. Based on the acquired MC-ACB images, we propose a mathematical model which helps to understand the distribution and accumulation pharmacokinetics of MNP. The MC-ACB showed a high time resolution to detect and monitor MNP, providing sequential images over the particle biodistribution. Utilizing the MC-ACB instrument, we assessed regions corresponding to the heart and liver, and we determined the MNP transfer rates between the bloodstream and the liver. The pharmacokinetic model resulted in having a strong correlation with the experimental data, suggesting that the MC-ACB is a valuable and accessible imaging device to assess in vivo and real-time pharmacokinetic features of MNP.


Assuntos
Diagnóstico por Imagem , Processamento de Imagem Assistida por Computador/métodos , Nanopartículas de Magnetita , Processamento de Sinais Assistido por Computador , Animais , Diagnóstico por Imagem/instrumentação , Diagnóstico por Imagem/métodos , Desenho de Equipamento , Compostos Férricos/farmacocinética , Masculino , Compostos de Manganês/farmacocinética , Tamanho da Partícula , Ratos , Ratos Wistar , Distribuição Tecidual
17.
Respirology ; 13(4): 594-8, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18410256

RESUMO

BACKGROUND AND OBJECTIVE: Pulmonary aspiration (PA) is a significant respiratory disease in children. However, the diagnosis of aspiration is often difficult owing to the poor efficacy of currently available diagnostic tests. The aim of this study was to assess in a mouse model the specificity of starch granule detection in BAL as a new method for detecting PA in children. METHODS: Twenty BALB/c mice were divided into the following groups according to the solution instilled into the airways: corn flour milk 7.5%-a source of starch (CM), Pseudomonas aeruginosa, normal saline and a control group. BAL was performed 2 days after instillation. Detection of starch granules and lipid-laden macrophages were compared in BAL. RESULTS: Starch granules were detected in BAL fluids from all mice in the CM group (food aspiration model), whereas no starch granules were detected in the other three groups, demonstrating a sensitivity and specificity of 100%. On the other hand, lipid-laden macrophages were found in all mice from all the groups studied. CONCLUSIONS: The detection of starch granules in BAL is a simple and highly specific method for the diagnosis of PA in an experimental model. Clinical studies using the starch granule detection method in BAL should be tested in at risk patients to evaluate the utility of this method for investigating PA.


Assuntos
Lavagem Broncoalveolar , Modelos Animais de Doenças , Pneumonia Aspirativa/diagnóstico , Animais , Técnicas de Diagnóstico do Sistema Respiratório , Feminino , Lipídeos , Macrófagos Alveolares , Camundongos , Camundongos Endogâmicos BALB C , Sensibilidade e Especificidade , Amido
19.
Pediatr Pulmonol ; 52(11): 1408-1413, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29027379

RESUMO

BACKGROUND: Severe asthma in children is a global health problem. Severe therapy-resistant asthma (STRA) in children is a major clinical challenge due to persistent symptoms despite high doses of corticosteroids and results in high public health costs. Omalizumab (anti-IgE monoclonal antibody) has been described as an effective add-on therapy in these patients. The characteristics of children with STRA from low- and middle-income countries have scarcely been reported, and no real-life study has been published on the effects of omalizumab in this group of patients. The aim of our study is to report the first clinical real-life experiences with omalizumab in Brazilian children with STRA. METHODS: Children (6-18 years old) from a referral center who were diagnosed with STRA were included in this retrospective study based on our clinical databases. The included children had undergone at least 6 months of omalizumab treatment and fulfilled the following initial criteria: 1) >6 years old; 2) a positive skin-prick test for at least one aeroallergen; and 3) a serum total IgE level between 30 and 1500 IU/mL. Clinical and lung function variables were analyzed before and after treatment. RESULTS: Fourteen children (mean age: 11.9 years; percentage female: 72%) were included in this study. Omalizumab treatment significantly increased control of the disease according to a standardized questionnaire administered at every visit (P < 0.0001), ceased hospitalizations in 70% (P = 0.02) of patients, and allowed 8/9 (89%) patients to be weaned off oral steroids (P = 0.004). CONCLUSIONS: In this retrospective report, the use of omalizumab in Brazilian children with STRA significantly improved disease control, decreased hospitalizations, and allowed suspension of continuous oral corticosteroids.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Omalizumab/uso terapêutico , Adolescente , Corticosteroides/uso terapêutico , Brasil , Criança , Países em Desenvolvimento , Resistência a Medicamentos , Feminino , Hospitalização , Humanos , Masculino , Qualidade de Vida , Testes Cutâneos , Inquéritos e Questionários
20.
Front Pediatr ; 5: 270, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29326908

RESUMO

BACKGROUND: An increase in the prevalence of overweight and asthma has been observed. Both conditions affect negatively lung function in adults and children. The aim of this study was to analyze the effect of overweight and asthma on lung function in children. METHODS: We designed a case-control study of healthy and asthmatic subjects nested within an epidemiological asthma prevalence study in children between 8 and 16 years of age. The effect of asthma and overweight on lung function was assessed by impulse oscillometry and spirometry obtained at baseline and 10-15 min after salbutamol. RESULTS: 188 children were recruited, 114 (61%) were asthmatics and 72 (38%) were overweight or obese. Children with asthma and overweight had a higher FVC (+1.16 z scores, p < 0.001) and higher FEV1 (+0.79 z scores, p = 0.004) and lower FEV1/FVC (-0.54 z scores, p = 0.008) when compared to healthy controls. Compared to normal weight asthmatics, the overweight had higher FVC (+0.78 z scores, p = 0.005) and lower FEV1/FVC (-0.50 z scores, p = 0.007). In the multivariate analysis, overweight was associated with an increase of 0.71 and 0.44 z scores in FVC and FEV1, respectively, and a reduction in FEV1/FVC by 0.40 z scores (p < 0.01 for all). Overweight had no effect on maximal flows and airway resistance at baseline, and this was not modified by inhalation of a bronchodilator. Asthma was also associated with higher post-BD FVC (0.45 z scores, p = 0.012) and FEV1 (0.35 z scores, p = 0.034) but not with FEV1/FVC and FEF25-75%. Two-way analysis of variance did not detect any interaction between asthma and overweight on lung function variables before or after bronchodilator. CONCLUSION: Our results suggest that asthma and overweight are independently associated with airway dysanaptic growth in children which can be further scrutinized using impulse oscillometry. Overweight contributed more to the reduction in FEV1/FVC than asthma in children without increasing airway resistance. Spirometry specificity and sensitivity for obstructive diseases may be reduced in populations with high prevalence of overweight. Adding impedance oscillometry to spirometry improves our understanding of the ventilatory abnormalities in overweight children.

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