RESUMO
Allergic rhinitis (AR) is a type I hypersensitivity mediated by dominant T helper 2 (Th2) response over the Th1 response after re-exposure to a specific allergen. Currently, socio-economic cost evoked by AR is quickly increasing since the prevalence of AR is gradually increasing in all ages worldwide. Several probiotic Lactobacillus strains have been described with potential immunomodulatory effects against type I hypersensitivity such as AR. Thus, the aim of the present work was to characterize basic probiotic property and immunomodulatory role of newly isolated Lactobacillus strains from Kimchi, a traditional fermented Korean food, in AR. Among the identified strains, Lactiplantibacillus plantarum NR16 revealed to be a powerful Th1 inducer since immune cells co-cultured with NR16 produced the highest quantity of interferon-γ (IFN-γ) and interleukin-12 (IL-12) but secreted a low amount of IL-4 in vitro. Therefore, NR16 was selected for the following assays conducted with mice with birch pollen-induced AR. Oral administration of NR16 reduced airway hyperresponsiveness and leukocyte infiltration in lesions of mice. In conclusion, oral administration of NR16 may mitigate symptoms of AR by inducing Th1 immune response, which might rebalance Th2/Th1 ratio by decreasing Th2 cytokine production in specific lesions of mucosa.
Assuntos
Alimentos Fermentados , Rinite Alérgica , Administração Oral , Alérgenos , Animais , Citocinas , Lactobacillus , Camundongos , Camundongos Endogâmicos BALB C , Rinite Alérgica/tratamento farmacológico , Células Th2RESUMO
BACKGROUND AND OBJECTIVE: We evaluated inattention and behavioural outcomes following surgery versus watchful waiting (WW) in school-aged children with mild obstructive sleep apnoea (OSA). METHODS: A prospective randomized controlled study was performed in pre-pubertal children aged 6-11 years with polysomnography (PSG)-confirmed mild OSA. They were assigned randomly to early surgical intervention (ES) or WW. The surgical intervention consisting of tonsillectomy with or without adenoidectomy and turbinate reduction was carried out within 4-6 weeks after randomization. Both groups underwent PSG, attention and behavioural assessment and review by an otorhinolaryngologist at baseline and 9-month follow-up. The primary outcome was omission T score from Conners' continuous performance test (CPT). Secondary outcomes were parent-reported behaviours, quality of life, symptoms and PSG parameters. RESULTS: A total of 114 participants were randomized. Data of 35 subjects from the ES and 36 from the WW group were available for final analysis. No significant treatment effect could be found in all CPT parameters and behavioural outcomes. Nevertheless, significantly greater reductions were seen in PSG parameters (obstructive apnoea-hypopnoea index [-1.4 ± 2.0 cf. +0.3 ± 4.1/h, p = 0.038] and arousal index [-1.3 ± 4.4 cf. +1.4 ± 4.5/h, p = 0.013]) and OSA-18 total symptom score (-17.3 ± 19.7 cf. -3.6 ± 14.1, p = 0.001) in the ES group. Subjects who underwent surgery also had significantly greater weight gain (+3.3 ± 2.1 cf. +2.2 ± 1.5 kg, p = 0.014) and increase in systolic blood pressure (+5.1 ± 12.4 cf. -1.2 ± 8.7 mm Hg, p = 0.016). CONCLUSION: Despite improvements in PSG parameters and parent-reported symptoms, surgical treatment did not lead to parallel improvements in objective attention measures in school-aged children with mild OSA.
Assuntos
Qualidade de Vida , Apneia Obstrutiva do Sono , Adenoidectomia , Atenção , Criança , Humanos , Estudos Prospectivos , Apneia Obstrutiva do Sono/cirurgiaRESUMO
AIMS: In this study, we evaluated the therapeutic efficacy of selected probiotics in a mouse model of birch pollen (BP)-induced allergic rhinitis. METHODS AND RESULTS: Oral administration of Lactobacillus plantarum CJLP133 and CJLP243 ameliorated the symptoms of BP-induced allergic rhinitis by reducing airway hyperresponsiveness, and both the histological scores and the number of infiltrated cells in the nasal cavities and lungs. Compared with those from vehicle-treated mice, bronchoalveolar lavage fluid and draining lymph node samples from CJLP133 and CJLP243-administrated mice showed diminished numbers of immune cells, increased secretion of a Th1-type cytokine (IFN-γ) and decreased production of Th2-type cytokines (IL-4, IL-5 and IL-13). Consistent with these results, levels of IL-4, IL-5, IL-13, serum IgE and BP-specific serum IgG1 were decreased, whereas secretion of IFN-γ and BP-specific serum IgG2a was augmented upon administration of CJLP133 and CJLP243 in mice. CONCLUSION: Oral administration of L. plantarum CJLP133 and CJLP243 alleviates symptoms of BP-induced allergic rhinitis in mice by recovering Th1/Th2 balance via enhancement of the Th1-type immune response. SIGNIFICANCE AND IMPACT OF THE STUDY: Lactobacillus plantarum CJLP133 and CJLP243 have therapeutic effects on BP-induced allergic rhinitis in an animal model.
Assuntos
Betula/imunologia , Lactobacillus plantarum/fisiologia , Pólen/imunologia , Probióticos/administração & dosagem , Rinite Alérgica/tratamento farmacológico , Administração Oral , Animais , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/genética , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Humanos , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Rinite Alérgica/imunologiaRESUMO
AIMS: Atopic dermatitis (AD) is an allergic skin disease driven by the Th2-prone immune response. Therefore, a fundamental approach to restoring the Th1/Th2 balance is needed to treat AD. METHODS AND RESULTS: Eighteen different Lactobacillus strains isolated from Kimchi were screened to identify those that stimulated immune cells to secret Th1-type or Th2-type cytokines. Lactobacillus brevis NS1401 induced the greatest IFN-γ and IL-12 secretion and the least IL-4 production among the tested Lactobacillus strains. Furthermore, oral administration of heat-killed NS1401 ameliorated the symptoms of dust mite-induced AD in NC/Nga mice by decreasing the serum IgE level and reducing the number of mast cells and eosinophils in lesions. Also, the size and number of cells in the draining lymph nodes of NS1401-administered mice were significantly reduced. In agreement with these results, secretion of a Th1-type cytokine (IFN-γ) and allergen-specific IgG2a were increased, whereas secretion of Th2-type cytokines (IL-4, IL-5, and IL-10) and allergen-specific IgG1 were decreased upon administration of NS1401 in mice. CONCLUSIONS: Lactobacillus brevis NS1401 alleviates the symptoms of AD by restoring the Th1/Th2 balance through enhancing Th1-prone immunity. SIGNIFICANCE AND IMPACT OF THE STUDY: The immunomodulatory function of L. brevis NS1401 may provide effective new therapeutics against AD.
Assuntos
Brassica/microbiologia , Dermatite Atópica/microbiologia , Levilactobacillus brevis/imunologia , Probióticos/administração & dosagem , Pyroglyphidae/imunologia , Animais , Dermatite Atópica/imunologia , Feminino , Temperatura Alta , Humanos , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-12/genética , Interleucina-12/imunologia , Interleucina-4/imunologia , Levilactobacillus brevis/química , Levilactobacillus brevis/isolamento & purificação , Levilactobacillus brevis/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Probióticos/química , Pele/patologia , Células Th2/imunologiaRESUMO
UNLABELLED: We investigated the effects of skatole (3-methylindole), which is one of the indole derivatives on the biofilm formation of EHEC O157:H7. Notably, skatole (100 µg ml⻹) significantly reduced EHEC O157:H7 ATCC 43894 biofilm formation by 52% in 96-well polystyrene plates under quiescent conditions, with no effect on planktonic cell growth. The skatole sample was maintained in stable conditions for 24 h without degradation or evaporation via EHEC O157:H7 ATCC 43894. Importantly, skatole negatively triggered the expression of catalase in EHEC strains, as well as altered EHEC surface morphology. Our finding indicated that suppressed catalase activity via skatole might have been responsible for elevated endogenous oxidative stress and increment in oxidative metabolites might have led to damaged cell surfaces and a reduction in biofilm formation of EHEC O157:H7 ATCC 43894. SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings suggest that inefficient catalase activity of skatole-exposed enterohemorrhagic Escherichia coli (EHEC) O157:H7 ATCC 43894 may account for elevated endogenous oxidative stress, leading to damaged cell surfaces and reduction in biofilm formation. Our results also provide that skatole as a new candidate for bacterial signalling may be applied for inhibiting bacterial biofilms in food and feed industry.
Assuntos
Biofilmes/efeitos dos fármacos , Escherichia coli O157/efeitos dos fármacos , Estresse Oxidativo , Escatol/farmacologia , Animais , Humanos , Mucosa Intestinal/metabolismo , Intestinos/microbiologiaRESUMO
A high level of androstenone in porcine adipose tissue is a major factor contributing to boar taint. Porcine hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 (3ß-HSD, also known as HSD3B1) plays a key role in the hepatic metabolism that catalyzes androstenone to ß-androstenol. Therefore, 3ß-HSD is a candidate gene for boar taint. This study aimed to investigate functional 3ß-HSD polymorphisms in Duroc pigs. We found eight single nucleotide polymorphisms (SNPs) in the full-length porcine 3ß-HSD. Four of the SNPs had restriction enzyme sites, and we genotyped them in 147 uncastrated male Duroc pigs using a polymerase chain reaction-restriction fragment length polymorphism method. Pigs with the GG genotype at the g.165262G>A locus (SNP5) had significantly lower androstenone levels than did those with other genotypes (P = 0.030). SNP5 also was associated with differences in 3ß-HSD mRNA levels: pigs with the GG genotype had higher levels than those with other genotypes (P = 0.019). The SNP5 polymorphism could affect the hepatic catabolism of androstenone and consequently impact androstenone accumulation in the adipose tissue. Therefore, SNP5 in the 3ß-HSD of Duroc pigs could be a useful selective marker for decreasing boar taint.
Assuntos
Polimorfismo de Nucleotídeo Único , Esteroide Isomerases/genética , Sus scrofa/metabolismo , Tecido Adiposo/metabolismo , Animais , Castração , Feminino , Expressão Gênica , MasculinoRESUMO
AIMS: To evaluate: (i) the prevalence of habitual snoring (HS) in a large sample of children aged from birth to 36 months in 14 countries across Asia Pacific; and (ii) the different correlates associated with HS in Caucasians, Chinese and non-Chinese, non-Caucasian Asians. METHODS: This was a multi-centre, cross-sectional survey conducted across Asia Pacific. Parents/caregivers of 23,481 infants and toddlers completed an expanded version of the Brief Infant Sleep Questionnaire. We defined HS as snoring more than three nights per week. RESULTS: Chinese and non-Caucasian non-Chinese (NCNC) children had a lower prevalence of HS across the age range from birth to 3 years than their Caucasian counterparts (6.2% and 5.1% vs. 11%, P < 0.01). Boys had a higher prevalence of HS compared to girls (χ(2) = 98.5, P < 0.0001). History of prematurity (OR = 1.37-1.56, CI (1.1-2.17), P < 0.01) and gender (OR = 1.53-1.54, CI (1.26-1.85), P < 0.0001) were found to be significant predictors for HS. Current breastfeeding (OR = 0.69, CI (0.54-0.88), P < 0.005) and greater parental age (OR = 0.86, CI (0.78-0.96), P < 0.01) were protective against HS among NCNC children. HS was less prevalent in younger Chinese subjects (OR = 0.88, CI (0.84-0.93), P < 0.0001). In Caucasians, parents' education (OR = 0.78, CI (0.67-0.91), P < 0.005) and their not sleeping in the same room as their child (OR = 0.62, CI (0.45-0.86), P < 0.005) were negatively associated with parental report of HS. CONCLUSIONS: Prevalence of HS shows racial differences among countries across Asia Pacific. Future studies should assess craniofacial structure and body fat distribution as contributory factors for this differential prevalence.
Assuntos
Ronco/epidemiologia , Pré-Escolar , Intervalos de Confiança , Estudos Transversais , Ásia Oriental/epidemiologia , Feminino , Humanos , Lactente , Modelos Logísticos , Masculino , Inquéritos e QuestionáriosRESUMO
AIM: To investigate the effect of orlistat on endothelial function in obese adolescents. METHODS: Single-blind 10-week controlled trial of 67 normolipidaemic obese adolescents randomised into three groups. Group 1 (diet alone), Group 2 (diet and orlistat), Group 3 (diet, orlistat and exercise). Endothelial function measured by flow-mediated dilatation (FMD) of the brachial artery, anthropometric parameters, blood pressure, fasting blood lipids, insulin and glucose levels were recorded at baseline and at 10 weeks. RESULTS: Sixty four subjects completed the study. Groups were comparable at baseline. FMD increased significantly with orlistat (Groups 2 and 3) but not in Group 1. Orlistat treatment resulted in significantly reduced bodyweight, body mass index (BMI), waist circumference, total and low-density lipoprotein (LDL) cholesterol levels. High-density lipoprotein cholesterol levels were unchanged. Triglyceride and insulin levels were significantly reduced in all three groups. The reduction in cholesterols did not correlate with reductions in weight and BMI. A slight reduction of body fat, both with and without orlistat treatment, correlated with reduction in BMI after adjustment for baseline values. Blood pressure was unaltered by orlistat. Calorie intake was reduced with orlistat, and the decrease noted in % fat and increase in % carbohydrate was significant only in those taking orlistat. The addition of exercise (Group 3 compared with Group 2) altered no parameter. CONCLUSIONS: Orlistat improves endothelial function and reduces bodyweight, BMI, fasting total and LDL-cholesterol in obese adolescents when combined with dietary control. Improvement in endothelial function if maintained could reflect long-term cardiovascular benefit.
Assuntos
Fármacos Antiobesidade/farmacologia , Células Endoteliais/efeitos dos fármacos , Lactonas/farmacologia , Obesidade/tratamento farmacológico , Adolescente , Antropometria , Determinação da Pressão Arterial , Criança , Ingestão de Energia , Jejum/sangue , Feminino , Hong Kong , Humanos , Masculino , Atividade Motora , Obesidade/dietoterapia , OrlistateRESUMO
BACKGROUND AND OBJECTIVE: This study aimed to assess the applicability of the Global Lung Function Initiative (GLI) prediction equations for spirometry in Hong Kong children and to develop prediction equations based on the Generalized Additive Models for Location, Scale, and Shape (GAMLSS) modeling. METHODS: Healthy Chinese children and adolescents aged 6-17 years old were recruited from randomly selected schools to undergo spirometry. The measurements were transformed to z-score according to the GLI-2012 equations for South East (SE) Asians and the GLI-2022 global race-neutral equations. Prediction equations for spirometric indices were developed with GAMLSS modeling to identify predictors. RESULTS: A total of 886 children (477 boys) with a mean age of 12.5 years (standard deviation [SD] 3.3 years) were included. By the GLI-2012 SE Asian equations, positive mean z-scores were observed in forced expiratory volume in 1 s (FEV1 ) (boys: 0.138 ± SD 0.828; girls: 0.206 ± 0.823) and forced vital capacity (FVC) (boys: 0.160 ± 0.930; girls: 0.310 ± 0.895) in both sexes. Negative mean z-scores were observed in FEV1 /FVC ratio (boys: -0.018 ± 0.998; girls: -0.223 ± 0.897). In contrast, negative mean z-scores in FEV1 and FVC, and positive mean z-scores in FEV1 /FVC were observed when adopting the GLI-2022 race-neutral equations. The mean z-scores were all within the range of ±0.5. By GAMLSS models, age and height were significant predictors for all four spirometric indices, while weight was an additional predictor for FVC and FEV1 . CONCLUSION: Our study provided data supporting the applicability of the GLI prediction equations in Hong Kong Chinese children. The GLI-2012 equations may underestimate FEV1 and FVC, while the GLI-2022 equations may overestimate the parameters, but the differences lie within the physiological limits. By GAMLSS modeling, weight was an additional predictor for FVC and FEV1 .
Assuntos
População do Leste Asiático , Pulmão , Masculino , Feminino , Adolescente , Humanos , Criança , Hong Kong/epidemiologia , Valores de Referência , Volume Expiratório Forçado/fisiologia , Espirometria , Capacidade Vital/fisiologia , Pulmão/fisiologiaRESUMO
In patients with transfusion-dependent thalassemia (TDT), pulmonary function impairment has been reported but data are conflicting. Moreover, it remains unclear whether pulmonary dysfunction is associated with iron overload. This study aimed to evaluate the pulmonary function in patients with TDT and to investigate the associations between pulmonary dysfunction and iron overload. It was a retrospective observational study. 101 patients with TDT were recruited for lung function tests. The most recent ferritin levels (pmol/L) and the magnetic resonance imaging (MRI) measurements of the myocardial and liver iron status, as measured by heart and liver T2* relaxation time (millisecond, ms) respectively, were retrieved from the computerized medical records. Only data within 12 months from the lung function measurement were included in the analysis. The serum ferritin, and the cardiac and liver T2* relaxation time were the surrogate indexes of body iron content. The threshold of abnormality in lung function was defined as under 80% of the predicted value. 101 subjects were recruited with a mean age of 25.1 years (standard deviation (SD) 7.9 years). Thirty-eight (38%) and five (5%) demonstrated restrictive and obstructive lung function deficits, respectively. A weak correlation of FVC %Predicted and TLC %Predicted with MRI myocardial T2* relaxation time (rho = 0.32, p = 0.03 and rho = 0.33, p = 0.03 respectively) was observed. By logistic regression, MRI cardiac T2* relaxation time was negatively associated with restrictive lung function deficit (B - 0.06; SE 0.03; Odds ratio 0.94; 95% confidence interval (CI) 0.89-0.99; p = 0.023) after adjusting for age, sex and body mass index. Restrictive pulmonary function deficit was commonly observed in patients with TDT, and the severity potentially correlates with myocardial iron content. Monitoring of lung function in this group of patients, particularly for those with iron overload, is important.
Assuntos
Sobrecarga de Ferro , Talassemia , Humanos , Adulto , Ferro , Pulmão , FerritinasRESUMO
We previously reported the development of genomic-DNA-based high-resolution genotyping methods for SLA-DQB1 and DRB1. Here, we report the successful typing of SLA-DQA using similar methodological principles. We designed a method for comprehensive genotyping of SLA-DQA using intronic sequence information of SLA-DQA exon 2 that we had obtained from 12 animals with different SLA-DQB1 genotypes. We expanded our typing to 76 selected animals with diverse DQB1 and DRB1 genotypes, 140 random animals from 7 pig breeds, and 3 wild boars. This resulted in the identification of 17 DQA alleles with 49 genotypes. Two new alleles were identified from wild boars. Combine with SLA-DQB1, and DRB1 typing results, we identified 34 SLA class II haplotypes including 25 that were previously unreported.
Assuntos
Genes MHC da Classe II , Antígenos de Histocompatibilidade Classe II/genética , Suínos/genética , Suínos/imunologia , Animais , Sequência de Bases , Primers do DNA/genética , DNA Complementar/genética , Éxons , Técnicas de Genotipagem/métodos , Haplótipos , Antígenos de Histocompatibilidade Classe I , Íntrons , Dados de Sequência Molecular , Filogenia , Polimorfismo Genético , Homologia de Sequência do Ácido NucleicoRESUMO
BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the aerobic capacity of children 3 years after they were diagnosed with severe acute respiratory syndrome (SARS). METHODS: Twenty-seven patients who completed both pulmonary function and maximal aerobic capacity tests at 6 and 15 months after the acute illness were invited to return for reassessment. RESULTS: Twenty-one patients (median age 18.2 years, interquartile range (IQR) 16.5-19.7) completed all investigations at 36 months. Pulmonary function was normal in all patients. Maximal aerobic capacity, peak oxygen pulse (peak VO(2) ) and ventilatory anaerobic threshold showed significant improvements compared with values measured at 6 months in both boys and girls. In girls, ventilatory efficiency (ventilatory equivalents for oxygen and carbon dioxide) and perfusion of the lungs (end-tidal partial carbon dioxide pressure) had not increased further compared with the values measured at 15 months. Although peak VO(2) improved further at 36 months in patients with or without persistent radiological abnormalities, the values were 68% (IQR 50-84) and 74% (IQR 60-99), respectively, of those for normal control subjects. CONCLUSIONS: There were improvements in aerobic capacity at 36 months in children affected by SARS; however, the measured values remained suboptimal.
Assuntos
Exercício Físico/fisiologia , Resistência Física/fisiologia , Síndrome Respiratória Aguda Grave/fisiopatologia , Adolescente , Limiar Anaeróbio/fisiologia , Feminino , Seguimentos , Frequência Cardíaca/fisiologia , Humanos , Pulmão/fisiopatologia , Masculino , Consumo de Oxigênio/fisiologia , Estudos Prospectivos , Testes de Função Respiratória , Adulto JovemRESUMO
Association between asthma control and cardiovascular disease (CVD) remains highly plausible as the two are related to chronic systemic inflammation. Children with physician-diagnosed asthma and matched healthy controls underwent endothelial function assessment. Repeat measurements were performed in uncontrolled asthmatics after initiation or up-titration of inhaled corticosteroids (ICS), compared to those with well-controlled asthma without ICS therapy. We found that children with uncontrolled asthma had inferior endothelial function compared to matched healthy controls. Enhancement in endothelial function, lung function and symptom control was observed in uncontrolled asthmatics after initiation or up-titration of inhaled corticosteroids (ICS). These results provided further evidence of a likely relationship between asthma control and cardiovascular health.
Assuntos
Antiasmáticos , Asma , Criança , Humanos , Antiasmáticos/uso terapêutico , Administração por Inalação , Asma/tratamento farmacológico , Corticosteroides/uso terapêutico , Inflamação/tratamento farmacológicoRESUMO
OBJECTIVE: To compare the levels of different urinary catecholamines amongst paediatric patients with and without sleep-disordered breathing (SDB). METHODS: Literature searches were conducted on PubMed and EMBASE until 25/06/2022. Inclusion criteria were original human studies, English language, paediatric subjects diagnosed with SDB/obstructive sleep apnoea (OSA). The quality of studies was assessed by the Newcastle-Ottawa Quality Assessment (NOSGEN). The registered number of this study on the International Prospective Register of Systematic Reviews (PROSPERO) is CRD42022332939. The main outcome measured was standardised mean difference (SMD) of urinary catecholamine between subjects with and without SDB, between those with and without OSA, and also between subjects with mild OSA and those with moderate/ severe OSA. Sensitivity analyses were performed to avoid bias. RESULTS: 9 studies (8 cross-sectional and 1 cohort study) with a total of 838 subjects, were included in the quantitative analysis. Urine level of noradrenaline was higher in patients with SDB, which included primary snoring (PS), when compared to controls: SMD = 0.86 (95%CI=0.32-1.41; I2=85%, P=0.002). The levels of urinary noradrenaline and adrenaline were higher in children with OSA when compared to controls: SMD = 1.45 (95%CI=0.91-2.00; I2=75%, P < 0.001); SMD = 1.84 (0.00-3.67; I2=97%, P=0.05). Urine level of noradrenaline was higher in subjects with moderate/severe OSA compared to the mild OSA: SMD = 0.55 (95%CI=0.10-1.00; I2=0%, P=0.02). Urinary dopamine was not associated with SDB regardless of severity. CONCLUSIONS: Urinary noradrenaline was higher in all patients with SDB. Subjects with OSA, a more severe form of SDB, had higher urine levels of noradrenaline and adrenaline. Hence, noradrenaline and adrenaline may be markers of sympathetic overtone in patients with SDB and could potentially act as surrogate markers for SDB complications. Further studies are needed to assess this association.
Assuntos
Síndromes da Apneia do Sono , Apneia Obstrutiva do Sono , Humanos , Criança , Catecolaminas , Estudos Transversais , Estudos de Coortes , Síndromes da Apneia do Sono/complicações , Apneia Obstrutiva do Sono/complicações , Biomarcadores/urina , Norepinefrina , EpinefrinaRESUMO
OBJECTIVES: To examine the prevalence and correlates of nocturnal enuresis (NE) in primary school children, and to compare the prevalence of NE in children with and those without obstructive sleep apnea (OSA). STUDY DESIGN: Parents of children aged 6-11 years completed a questionnaire eliciting information on sleep-related symptoms, demography, and family and past medical history. Children screened due to high risk for OSA, along with a randomly chosen low-risk group, underwent overnight polysomnography (PSG). RESULTS: A total of 6147 children (3032 girls) were studied. The overall prevalence of NE (≥1 wet night/month) was 4.6% (6.7% of boys and 2.5% of girls). Boys had a significantly greater prevalence across all age groups. In 597 children (215 girls) who underwent PSG, the prevalence of NE was not greater in children with OSA, but was increased with increasing severity of OSA in girls only. Boys with NE had longer deep sleep duration. Sex and sleep-related symptoms were associated with NE. CONCLUSIONS: This community-based study demonstrated a sex-associated prevalence of NE in relation to increasing OSA severity.
Assuntos
Enurese Noturna/epidemiologia , Apneia Obstrutiva do Sono/complicações , Criança , Progressão da Doença , Enurese , Feminino , Seguimentos , Hong Kong/epidemiologia , Humanos , Masculino , Enurese Noturna/etiologia , Enurese Noturna/fisiopatologia , Polissonografia , Prevalência , Fatores de Risco , Sono/fisiologia , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/fisiopatologia , Inquéritos e Questionários , Fatores de TempoRESUMO
Although it is presumed that the integration of HIV-1 into the genome of infected CD4+ T lymphocytes allows viral persistence, there has been little direct evidence that CD4+ T cells with integrated provirus function as a latent reservoir for HIV-1 in infected individuals. Using resting CD4+ T-cell populations of extremely high purity and a novel assay that selectively and unambiguously detects integrated HIV-1, we show that resting CD4+ T cells harbouring integrated provirus are present in some infected individuals. However, these cells do not accumulate within the circulating pool of resting CD4+ T cells in the early stages of HIV-1 infection and do not accumulate even after prolonged periods in long-term survivors of HIV-1 infection. These results suggest that because of viral cytopathic effects and/or host effector mechanisms, productively infected CD4+ T cells do not generally survive for long enough to revert to a resting memory state in vivo.
Assuntos
Linfócitos T CD4-Positivos/virologia , DNA Viral/análise , Infecções por HIV/virologia , HIV-1/genética , Provírus/genética , Sequência de Bases , Separação Celular , Primers do DNA , Infecções por HIV/sangue , HIV-1/isolamento & purificação , Humanos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Integração Viral , Latência ViralRESUMO
We examined the pathogenic significance of the latent viral reservoir in the resting CD4+ T cell compartment of HIV-1-infected individuals as well as its involvement in the rebound of plasma viremia after discontinuation of highly active anti-retroviral therapy (HAART). Using heteroduplex mobility and tracking assays, we show that the detectable pool of latently infected, resting CD4+ T cells does not account entirely for the early rebounding plasma HIV in infected individuals in whom HAART has been discontinued. In the majority of patients examined, the rebounding plasma virus was genetically distinct from both the cell-associated HIV RNA and the replication-competent virus within the detectable pool of latently infected, resting CD4 + T cells. These results indicate the existence of other persistent HIV reservoirs that could prompt rapid emergence of plasma viremia after cessation of HAART and underscore the necessity to develop therapies directed toward such populations of infected cells.
Assuntos
Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1 , Viremia , Latência Viral , Adulto , Linfócitos T CD4-Positivos/virologia , Infecções por HIV/sangue , Humanos , Pessoa de Meia-Idade , RNA Viral/sangue , Recidiva , Replicação ViralRESUMO
The antigenic polymorphism of HIV-1 is a major obstacle in developing an effective vaccine. Accordingly, we screened random peptide libraries (RPLs) displayed on phage with antibodies from HIV-infected individuals and identified an array of HIV-specific epitopes that behave as antigenic mimics of conformational epitopes of gp120 and gp41 proteins. We report that the selected epitopes are shared by a collection of HIV-1 isolates of clades A-F. The phage-borne epitopes are immunogenic in rhesus macaques, where they elicit envelope-specific antibody responses. Upon intravenous challenge with 60 MID50 of pathogenic SHIV-89.6PD, all monkeys became infected; however, in contrast to the naive and mock-immunized monkeys, four of five mimotope-immunized monkeys experienced lower levels of peak viremia, followed by viral set points of undetectable or transient levels of viremia and a mild decline of CD4+ T cells, and were protected from progression to AIDS-like illness. These results provide a new approach to the design of broadly protective HIV-1 vaccines.
Assuntos
Vacinas contra a AIDS/farmacologia , Infecções por HIV/prevenção & controle , HIV-1/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vacinas contra a AIDS/genética , Vacinas contra a AIDS/imunologia , Sequência de Aminoácidos , Animais , Epitopos/administração & dosagem , Epitopos/genética , Anticorpos Anti-HIV/biossíntese , Antígenos HIV/administração & dosagem , Antígenos HIV/genética , Infecções por HIV/imunologia , HIV-1/genética , Humanos , Macaca mulatta , Biblioteca de Peptídeos , Vacinas contra a SAIDS/genética , Vacinas contra a SAIDS/imunologia , Vacinas contra a SAIDS/farmacologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologiaRESUMO
The size of the pool of resting CD4+ T cells containing replication-competent HIV in the blood of patients receiving intermittent interleukin (IL)-2 plus highly active anti-retroviral therapy (HAART) was significantly lower than that of patients receiving HAART alone. Virus could not be isolated from the peripheral blood CD4+ T cells in three patients receiving IL-2 plus HAART, despite the fact that large numbers of resting CD4+ T cells were cultured. Lymph node biopsies were done in two of these three patients and virus could not be isolated. These results indicate that the intermittent administration of IL-2 with continuous HAART may lead to a substantial reduction in the pool of resting CD4+ T cells that contain replication-competent HIV.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/virologia , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Interleucina-2/uso terapêutico , Estudos Transversais , Inibidores da Protease de HIV/uso terapêutico , HIV-1/patogenicidade , Humanos , Interleucina-2/farmacologia , Linfonodos/virologia , Contagem de Linfócitos/efeitos dos fármacos , RNA Viral/sangue , Replicação Viral/efeitos dos fármacosRESUMO
In recent years, adverse health effects of chemicals from electronic waste (e-waste) have been reported. However, little is known about the genotoxic effects of chemicals in e-waste. In the present study, air concentrations of the toxic metals at e-waste and control sites were analyzed using inductively-coupled plasma mass spectrometry. Levels of toxic metals (lead, copper and cadmium) in blood and urine were detected using atomic absorption spectrophotometry in 48 exposed individuals and 56 age- and sex-matched controls. The frequencies of lymphocytic micronucleated binucleated cells (MNBNCs) were determined using a cytokinesis-block micronucleus assay. Results indicated that blood lead levels were significantly higher in the exposed group (median: 11.449 µg/dL, 1st/3rd quartiles: 9.351-14.410 µg/dL) than in the control group (median: 9.104 µg/dL, 1st/3rd quartiles: 7.275-11.389 µg/dL). The exposed group had higher MNBNCs frequencies (median: 4.0 per thousand, 1st/3rd quartiles: 2.0-7.0 per thousand) compared with the controls (median: 1.0 per thousand, 1st/3rd quartiles: 0.0-2.0 per thousand). Additionally, MNBNCs frequencies and blood lead levels were positively correlated (r = 0.254, p<0.01). Further analysis suggested that a history of working with e-waste was a predictor for increased blood lead levels and MNBNCs frequencies in the subjects. The results suggest that both the living and occupational environments at the e-waste site may be risk factors for increased MNBNCs frequencies among those who are exposed.