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1.
Cureus ; 16(1): e52577, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38371029

RESUMO

Background Asthma represents one of the most common diseases in childhood, with a prevalence ranging between 9% and 13% in Portugal. Therefore, it holds significant importance in pediatric health. While existing studies have shed light on asthma in the Portuguese population, they have predominantly concentrated on urban centers, with the population of Alto Minho remaining underrepresented in the literature. This study aims to understand the main factors of exposure, exacerbation, and the most prevalent allergens in a pediatric sample from the Alto Minho Local Health Unit, Portugal. Methodology A retrospective cohort study was conducted among 239 pediatric asthma patients aged between five and 18 years at the Alto Minho Health Center. Data on demographics, clinical information, family history, environmental exposures, exacerbating factors, and prick test results were analyzed. Results Of the 239 patients, 64.44% were male and 35.56% were female. The majority of the sample exhibited a normal body mass index (82.17%) and a family history of atopy (66.67%). Noteworthy patterns emerged in comorbidities, notably an increased association with allergic rhinitis, the most frequent concomitant atopic pathology (79.50%), followed by atopic dermatitis (27.61%) and food allergy (10.88%). Sensitization to dust mites, particularly Dermatophagoides pteronyssinus, was widespread among the participants. Environmental exposures were marked by significant factors such as proximity to plants and trees, soft toys, and living in rural areas. Exacerbating factors included common triggers such as exercise, seasonal variations, and even laughter. Statistically significant associations were found between atopic comorbidities, exacerbation factors, exposure factors, and prick test results. Conclusions Our findings align with global trends, emphasizing the prevalence of atopic pathologies in pediatric asthma. Sensitization patterns and environmental exposures are indicative of regional influences. Study limitations include sample size and data standardization issues. Despite these limitations, the study significantly contributes to understanding pediatric asthma in Alto Minho, offering valuable insights for prompt diagnosis and targeted treatments.

2.
J Biol Chem ; 286(25): 22235-42, 2011 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-21531728

RESUMO

Human factor H (HufH), a key inhibitor of the alternative pathway of complement, binds to Neisseria gonorrhoeae and constitutes an important mechanism of human-specific complement evasion. The C-terminal domain 20 of HufH contains the binding site for sialylated gonococci. We exploited differences in amino acid sequences between human and non-binding chimpanzee fH domain 20 to create cross-species mutations to define amino acids important for binding to sialylated gonococci. We used fH/Fc fusion constructs that contained contiguous fH domains 18-20 fused to Fc fragments of murine IgG2a. The Fc region was used both as a tag for detection of each fusion molecule on the bacterial surface and as an indicator for complement-dependent killing. Arg-1203 was critical for binding to both porin (Por) B.1A and PorB.1B strains. Modeling of the R1203N human-to-chimpanzee mutation using the crystal structure of HufH19-20 as a template showed a loss of positive charge that protrudes at the C terminus of domain 20. We tested the functional importance of Arg-1203 by incubating sialylated gonococci with normal human serum, in the presence of wild-type HufH18-20/Fc or its R1203A mutant. Gonococci bound and were killed by wild-type HufH18-20/Fc but not by the R1203A mutant. A recombinant fH/Fc molecule that contained chimpanzee domain 20, humanized only at amino acid 1203 (N1203R) also bound to sialylated gonococci and restored killing. These findings provide further insights into the species specificity of gonococcal infections and proof-of-concept of a novel therapeutic approach against gonorrhea, a disease rapidly becoming resistant to conventional antibiotics.


Assuntos
Fator H do Complemento/metabolismo , Ácido N-Acetilneuramínico/metabolismo , Neisseria gonorrhoeae/metabolismo , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Arginina , Sítios de Ligação , Fator H do Complemento/química , Fator H do Complemento/genética , Fator H do Complemento/farmacologia , Heparina/farmacologia , Humanos , Fragmentos Fc das Imunoglobulinas/genética , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Mutação , Neisseria gonorrhoeae/efeitos dos fármacos , Pan troglodytes , Ligação Proteica/efeitos dos fármacos , Estrutura Terciária de Proteína , Especificidade da Espécie
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