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1.
Med J Malaysia ; 79(4): 408-413, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39086337

RESUMO

INTRODUCTION: Febrile seizures in children can be associated with various underlying conditions, including COVID-19. Differentiating COVID-19 and non-COVID-19 related febrile seizures is crucial for tailored patient management and for implementing appropriate infection control measures to prevent nosocomial transmission. This study aimed to describe the clinical features of children hospitalised for COVID-19 and non-COVID-19 febrile seizures and to identify factors that differentiate between the two groups. MATERIALS AND METHODS: This retrospective cross-sectional study involved children aged 6 months to 6 years who were hospitalised for febrile seizures in Hospital Tuanku Ja'afar Seremban (HTJS) from January 2021 to June 2022. Descriptive statistics were used to summarise the differences in demographics and clinical presentations. Logistic regression analyses were performed to identify factors associated with COVID-19 and non-COVID-19 febrile seizures. RESULTS: Of the 345 patients (median age 22 months, IQR 15- 32; 59.7% were males) included in the study, 130 (37.7%) tested positive for COVID-19, while 215 (62.3%) tested negative. There were no significant differences between both groups based on age, comorbidities, history of febrile seizures, seizure types, temperature on arrival, cough and rhinorrhoea. Multivariate analysis revealed that a family history of febrile seizures and leucocytosis were associated with increased odds of non-COVID-19 febrile seizures. In contrast, lymphopenia was associated with decreased odds. CONCLUSION: The clinical presentation of COVID-19 and non- COVID-19 febrile seizures are remarkably similar, highlighting the importance of including COVID-19 screening in febrile seizures workup. Full blood count readings may be potentially useful for differentiating between these conditions.


Assuntos
COVID-19 , Convulsões Febris , Humanos , COVID-19/complicações , COVID-19/diagnóstico , Masculino , Convulsões Febris/diagnóstico , Feminino , Estudos Retrospectivos , Lactente , Pré-Escolar , Estudos Transversais , Criança , SARS-CoV-2 , Hospitalização , Diagnóstico Diferencial
2.
Tech Coloproctol ; 27(9): 713-719, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37039927

RESUMO

The transanal approach to ileal pouch-anal anastomosis (Ta-IPAA) for ulcerative colitis was introduced in 2015 and has since been shown to be a safe and feasible technique, although the impact of this approach on patient function remains unclear. A systematic literature review was performed to identify studies exploring functional outcomes and quality of life after Ta-IPAA. Seven papers were identified, which all demonstrated satisfactory functional outcomes after Ta-IPAA as measured by tools such as Cleveland Global Quality of Life (CGQOL), Oresland Score (OS), Pouch Functional Score (PFS), and Inflammatory Bowel Disease Questionnaire (IBDQ). Many gaps in the literature were identified including paucity of follow-up data beyond the 1-year mark, lack of fertility and fecundity assessment as functional outcomes, and limited evaluation of objective physiologic anal sphincter function. The Ta-IPAA therefore shows promise for good functional results in the short-term, although further research will be required to evaluate the stability of function over time as the technique becomes increasingly integrated into modern surgical practice.


Assuntos
Colite Ulcerativa , Bolsas Cólicas , Proctocolectomia Restauradora , Humanos , Colite Ulcerativa/cirurgia , Qualidade de Vida , Resultado do Tratamento , Proctocolectomia Restauradora/efeitos adversos , Proctocolectomia Restauradora/métodos , Anastomose Cirúrgica , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
3.
Hong Kong Med J ; 28(3): 230-238, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35667869

RESUMO

BACKGROUND: Neoadjuvant chemoradiotherapy is a standard treatment for locally advanced rectal cancer, for which pathological complete response is typically used as a surrogate survival endpoint. Neoadjuvant rectal score is a new biomarker that has been shown to correlate with survival. The main objectives of this study were to investigate factors contributing to pathological complete response, to validate the prognostic significance of neoadjuvant rectal score, and to investigate factors associated with a lower neoadjuvant rectal score in a cohort of Hong Kong Chinese. METHODS: Data of patients with locally advanced rectal cancer who received neoadjuvant chemoradiotherapy from August 2006 to October 2018 were retrieved from hospital records and retrospectively analysed. RESULTS: Of 193 patients who had optimal response to neoadjuvant chemoradiotherapy and surgery, tumour down-staging was the only independent prognostic factor that predicted pathological complete response (P<0.0001). Neoadjuvant rectal score was associated with overall survival (hazard ratio [HR]=1.042, 95% confidence interval [CI]=1.021-1.064; P<0.0001), disease-free survival (HR=1.042, 95% CI=1.022-1.062; P<0.0001), locoregional recurrence-free survival (HR=1.070, 95% CI=1.039-1.102; P<0.0001) and distant recurrence-free survival (HR=1.034, 95% CI=1.012-1.056; P=0.002). Patients who had pathological complete response were associated with a lower neoadjuvant rectal score (P<0.0001), but pathological complete response was not associated with survival. For patients with intermediate neoadjuvant rectal scores, late recurrences beyond 72 months from diagnosis were observed. CONCLUSION: Neoadjuvant rectal score is an independent prognostic marker of survival and disease recurrence in a cohort of Hong Kong Chinese patients who received neoadjuvant chemoradiotherapy for locally advanced rectal cancer.


Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Biomarcadores , Quimiorradioterapia , Intervalo Livre de Doença , Hong Kong , Humanos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Estudos Retrospectivos , Resultado do Tratamento
4.
Med J Malaysia ; 77(3): 300-305, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35638485

RESUMO

INTRODUCTION: The COVID-19 pandemic is a global health crisis that has resulted in a massive disease burden worldwide. Mass vaccination plays an important role in controlling the spread and severity of COVID-19 infections worldwide. MATERIALS AND METHODS: A cross-sectional study was conducted in Hospital Tuanku Ja'afar Seremban between 1 March 2021 and 4 May 2021 to describe the adverse events (AE) following BNT162b2 (Pfizer-BioNTech) vaccination. Healthcare personnel who received at least one dose of the vaccine were invited to complete an online questionnaire. RESULTS: Of 2282 analysed samples, AE were experienced in up to 64.5% (n=1472) of the study participants. Most AE were encountered after the second dose (56.5%, n=832). Pain at the injection site (41.5%, n=944), fever (35.1%, n=798) and lethargy (34.8%, n=792) were the most commonly reported AE. Severe AEFI were reported in a minority (2.9%, n=68). There were no documented anaphylaxis, vaccine-induced thrombosis, or myocarditis. The proportion of female recipients and recipients with a history of allergy were higher in the AE group compared to the non-AE group. CONCLUSION: Our study reinforces the safety of the BNT162b2 mRNA vaccine in the local population. The main adverse events were mild, although they occurred in most patients.


Assuntos
COVID-19 , Vacinas , Vacina BNT162 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Estudos Transversais , Feminino , Pessoal de Saúde , Humanos , Malásia/epidemiologia , Pandemias , RNA Mensageiro , Vacinação/efeitos adversos , Vacinação/métodos , Vacinas Sintéticas , Vacinas de mRNA
5.
HIV Med ; 22(7): 527-537, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33751761

RESUMO

OBJECTIVES: Individual kidney tubule biomarkers are associated with chronic kidney disease (CKD) risk in people living with HIV (PLWH). Whether a combination of kidney biomarkers can be integrated into informative summary scores for PLWH is unknown. METHODS: We measured eight urine biomarkers of kidney tubule health at two visits over a 3-year period in 647 women living with HIV in the Women's Interagency Health Study. We integrated biomarkers into factor scores using exploratory factor analysis. We evaluated associations between CKD risk factors and factor scores, and used generalized estimating equations to determine associations between factor scores and risk of incident CKD. RESULTS: Factor analysis identified two unique factor scores: a tubule reabsorption score comprising alpha-1-microglobulin, beta-2-microglobulin and trefoil factor-3; and a tubule injury score comprising interleukin-18 and kidney injury molecule-1. We modelled the two factor scores in combination with urine epidermal growth factor (EGF) and urine albumin. Predominantly HIV-related CKD risk factors were independently associated with worsening tubule reabsorption scores and tubule injury scores. During a median follow-up of 7 years, 9.7% (63/647) developed CKD. In multivariable time-updated models that adjusted for other factor scores and biomarkers simultaneously, higher tubule reabsorption scores [risk ratio (RR) = 1.27, 95% confidence interval (CI): 1.01-1.59 per 1 SD higher time-updated score], higher tubule injury scores (RR = 1.36, 95% CI: 1.05-1.76), lower urine EGF (RR = 0.75, 95% CI: 0.64-0.87), and higher urine albumin (RR = 1.20, 95% CI: 1.02-1.40) were jointly associated with risk of incident CKD. CONCLUSIONS: We identified two novel and distinct dimensions of kidney tubule health that appear to quantify informative metrics of CKD risk in PLWH.


Assuntos
Infecções por HIV , Insuficiência Renal Crônica , Biomarcadores , Feminino , Taxa de Filtração Glomerular , Infecções por HIV/complicações , Humanos , Rim , Túbulos Renais/lesões , Insuficiência Renal Crônica/epidemiologia , Fatores de Risco
6.
Hong Kong Med J ; 26(6): 492-499, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33323537

RESUMO

OBJECTIVES: Cross-border reproductive care (CBRC) is an increasingly common global phenomenon, but there is a lack of information regarding its frequency among residents of Hong Kong. This study aimed to evaluate the use of CBRC and the factors affecting its use among residents of Hong Kong. METHODS: This cross-sectional questionnaire study collected data from 1204 women with infertility who attended Hong Kong Hospital Authority and Family Planning Association infertility clinics. RESULTS: In total, 178 women (14.8% of all respondents) had used CBRC. Among respondents who had not used CBRC, 36.3% planned to use or would consider it. The main factors influencing the likelihood of using CBRC among women with infertility in Hong Kong use were long waiting times in the public sector and high cost in the private sector. Taiwan was the most preferred destination for CBRC (69.6% of respondents). Most information concerning CBRC was accessed via the internet. More than two thirds of respondents believed that the government in Hong Kong should formulate some regulations or guidance regarding CBRC. CONCLUSION: Nearly one in six women with infertility in Hong Kong had used CBRC. Among women who had not used CBRC, more than one third planned to use or would consider it. The main factors influencing the likelihood of CBRC use were long waiting times in the public sector and high cost in the private sector. These results will help clinicians to more effectively counsel patients considering CBRC and facilitate infertility services planning by authorities in Hong Kong.


Assuntos
Infertilidade Feminina/terapia , Turismo Médico/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Serviços de Saúde Reprodutiva/estatística & dados numéricos , Adulto , Estudos Transversais , Feminino , Hong Kong , Humanos , Pessoa de Meia-Idade , Setor Privado/estatística & dados numéricos , Setor Público/estatística & dados numéricos , Inquéritos e Questionários
7.
Br J Dermatol ; 181(2): 290-295, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30706447

RESUMO

BACKGROUND: Childhood atopic dermatitis (AD) is a chronic inflammatory disease associated with pruritus and sleep loss. It is important to evaluate quality-of-life (QoL) impairment objectively in atopic diseases in children. OBJECTIVES: To investigate the utility of the Pediatric Allergic Disease Quality of Life Questionnaire (PADQLQ) in children with eczema. METHODS: PADQLQ, Patient-Oriented Eczema Measure (POEM, a short-term subjective symptom score), Nottingham Eczema Severity Score (NESS, a long-term subjective symptom score) and Children's Dermatology Life Quality Index (CDLQI, a short-term subjective symptom score) were compared and correlations evaluated. RESULTS: PADQLQ, POEM, NESS and CDLQI correlated well with each other (n = 132 sets; Spearman correlations: rho = 0·48-0·70, P < 0·001). A Bland-Altman plot showed a reasonably good agreement between CDLQI and PADQLQ. PADQLQ showed that symptoms of asthma, allergic conjunctivitis and allergic rhinitis were present in 20-30%, 45-71% and 58-67% of children with AD, respectively. Nevertheless, there was no association of eczema symptomatology by POEM or NESS with the severity of other allergic diseases. CONCLUSIONS: PADQLQ correlates well with AD-specific severity and QoL scores and reflects all allergic symptoms that holistically influence QoL in children with AD. PADQLQ is hence a composite severity score in terms of clinical symptomatology and QoL impairment for AD.


Assuntos
Dermatite Atópica/diagnóstico , Qualidade de Vida , Índice de Gravidade de Doença , Adolescente , Criança , Dermatite Atópica/complicações , Dermatite Atópica/psicologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Inquéritos e Questionários
8.
Med J Malaysia ; 74(3): 191-197, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31256172

RESUMO

BACKGROUND: It is not uncommon that anxiety and depression occur in patients with cancers, and past researches have shown that the quality of life of patients is negatively affected. This study aims to determine the prevalence of anxiety and depression of patients with haematological cancers in Malaysia and to investigate the possible association of these psychological symptoms with their quality of life. METHODS: This is a cross-sectional study where patients with haematological cancers attending two major hospitals were recruited. Anxiety and depression symptoms were assessed using the Hospital Anxiety and Depression scale (HADS). Quality of life (QoL) of these patients was measured using the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ C30). An overall summary QoL score in combination with financial difficulty score and global health score were used for analysis. RESULTS: A total of 319 patients were recruited. Thirty-three percent of patients had anxiety symptoms, 23.5% had depression symptoms. In summary the overall score of QoL is significantly lower in patients with higher scores for depression and anxiety, (p<0.05). Patients who exhibit anxiety symptoms were more frequently female, still undergoing treatment whereas patients who had higher depression scores were older and had acute leukemias or myeloproliferative neoplasms. Patients who have depression are significantly associated with a higher financial difficulty score, p<0.05. CONCLUSION: The poor quality of life in patients who have anxiety and depression should raise awareness amongst the health professions treating them so that additional support can be provided.


Assuntos
Ansiedade/epidemiologia , Depressão/epidemiologia , Neoplasias Hematológicas/psicologia , Qualidade de Vida , Adulto , Idoso , Estudos Transversais , Feminino , Neoplasias Hematológicas/patologia , Humanos , Malásia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores Socioeconômicos , Inquéritos e Questionários
9.
Clin Genet ; 93(5): 1022-1029, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29383714

RESUMO

This study examined the impact of disclosing subclassifications of genetic variants of uncertain significance (VUS) on behavioral intentions. We studied return of VUS results to 79 individuals with a cardiomyopathy-associated VUS, subclassified into VUS-high or VUS-low. Primary outcomes were perceived risk (absolute and comparative), perceived severity, perceived value of information, self-efficacy, decision regret, and behavioral intentions to share results and change behaviors. There was no significant difference between the 2 subclasses in overall behavioral intentions (t = 0.023, P = .982) and each of the individual items on the behavioral intentions scale; absolute (t = -1.138, P = .259) or comparative (t = -0.463, P = .645) risk perceptions; perceived value of information (t = 0.582, P = .563) and self-efficacy (t = -0.733, P = .466). Decision regret was significantly different (t = 2.148, P = .035), with VUS-low (mean = 17.24, SD = 16.08) reporting greater regret. Combining the subclasses, perceived value of information was the strongest predictor of behavioral intentions (ß = 0.524, P < .001). Participants generally understood the meaning of a genetic VUS result classification and reported satisfaction with result disclosure. No differences in behavioral intentions were found, but differences in decision regret suggest participants distinguish subclasses of VUS results. The perceived value of VUS may motivate recipients to pursue health-related behaviors.


Assuntos
Cardiomiopatias/genética , Exoma/genética , Predisposição Genética para Doença , Cardiomiopatias/fisiopatologia , Feminino , Aconselhamento Genético , Testes Genéticos , Variação Genética , Humanos , Masculino , Análise de Sequência de DNA , Incerteza
10.
Hong Kong Med J ; 29(2): 178-180, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37041068
13.
Hong Kong Med J ; 23(5): 441-5, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28126972

RESUMO

INTRODUCTION: Intravenous infusion of lignocaine has emerged in recent years as a feasible, cost-effective, and safe method to provide postoperative analgesia. There is, however, no literature about this perioperative pain control modality in Chinese patients. This study aimed to determine whether perioperative intravenous lignocaine safely reduces postoperative pain, shortens postoperative ileus, and reduces the length of hospital stay in laparoscopic colorectal surgery. METHODS: Between September 2012 and May 2015, 16 patients who underwent elective laparoscopic resection of colorectal cancer and received a 1% lignocaine infusion for 24 hours postoperatively were studied. After surgery, categorical pain scores were obtained immediately, followed by hourly pain scores at rest. Pain scores at rest and with mobilisation, and patient satisfaction score were documented on postoperative day 1. Return of bowel function was measured by time of first flatus and bowel opening. The patient's rehabilitation was assessed by time taken to tolerate diet, full mobilisation, and length of hospital stay. RESULTS: The median (interquartile range) self-reported pain scores at 2 hours and 6 hours after surgery were 1.5 (0-4) and 2 (0-3), respectively. The median pain scores at rest and mobilisation on postoperative day 1 were 1 (0-2.5) and 2 (2.5-5), respectively, with a median satisfaction score of 7.5 (7-9). The median times to first flatus and first bowel opening were 21 (18-35) hours and 3 (1-3) days, respectively. No patient had postoperative ileus. The median times to tolerating diet and mobilisation were 1 (1-1) day and 2 (2-3) days, respectively. The median postoperative stay was 6 (5-8) days. CONCLUSIONS: Intravenous lignocaine is a safe and effective postoperative analgesic in a Chinese population. It enhances the rehabilitation process for patients following laparoscopic resection of colorectal cancer.


Assuntos
Anestésicos Locais/uso terapêutico , Colectomia , Neoplasias Colorretais/reabilitação , Lidocaína/uso terapêutico , Dor Pós-Operatória/prevenção & controle , Idoso , Anestésicos Locais/administração & dosagem , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Infusões Intravenosas , Laparoscopia , Lidocaína/administração & dosagem , Masculino , Medição da Dor , Assistência Perioperatória , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Resultado do Tratamento
17.
Infection ; 42(2): 343-50, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24277597

RESUMO

PURPOSE: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infection in young children. However, there are limited data on severe RSV infection requiring pediatric intensive care unit (PICU) admission. This retrospective study described features of RSV-associated PICU admissions in Hong Kong and investigated factors for mortality and duration of PICU stay. METHODS: Children with laboratory-confirmed RSV infection and admitted to the PICUs of all eight government hospitals in Hong Kong between January 2009 and June 2011 were identified from computerized auditing systems and PICU databases. RSV in respiratory samples was detected by direct immunofluorescence and/or viral culture. The relationships between mortality and PICU duration and demographic and clinical factors were analyzed. RESULTS: A total of 118 (2.4 %) PICU admissions were identified among 4,912 RSV-positive pediatric cases in all hospitals. Sixty-five (55.6 %) patients were infants. PICU admissions were higher between October and March. Eight (6.8 %) patients died, but only two were infants. RSV-associated mortality was related to prior sick contact, presence of older siblings, neurodevelopmental conditions, chromosomal and genetic diseases, and bacterial co-infections, but none was significant following logistic regression analyses (odds ratio 9.36, 95 % confidence interval 0.91-96.03 for prior sick contact, p = 0.060). Chronic lung disease was the only risk factor for the duration of PICU admission (ß = 0.218, p = 0.017). CONCLUSIONS: The majority of RSV-infected children do not require PICU support. There is winter seasonality for RSV-associated PICU admission in Hong Kong. Prior sick contact is the only risk factor for RSV-associated mortality, whereas the presence of chronic lung disease is associated with longer PICU stay. The current risk-based approach of RSV prophylaxis may not be effective in reducing severe RSV infections.


Assuntos
Infecções por Vírus Respiratório Sincicial/epidemiologia , Vírus Sinciciais Respiratórios/isolamento & purificação , Infecções Respiratórias/epidemiologia , Pré-Escolar , Feminino , Hong Kong/epidemiologia , Hospitalização , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica , Masculino , Infecções por Vírus Respiratório Sincicial/microbiologia , Infecções por Vírus Respiratório Sincicial/mortalidade , Infecções Respiratórias/microbiologia , Infecções Respiratórias/mortalidade , Estudos Retrospectivos , Fatores de Risco
18.
Med J Malaysia ; 69(4): 149-50, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25500840

RESUMO

No abstract available.

19.
Diabetologia ; 56(6): 1291-305, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23532257

RESUMO

AIMS/HYPOTHESIS: Most genetic variants identified for type 2 diabetes have been discovered in European populations. We performed genome-wide association studies (GWAS) in a Chinese population with the aim of identifying novel variants for type 2 diabetes in Asians. METHODS: We performed a meta-analysis of three GWAS comprising 684 patients with type 2 diabetes and 955 controls of Southern Han Chinese descent. We followed up the top signals in two independent Southern Han Chinese cohorts (totalling 10,383 cases and 6,974 controls), and performed in silico replication in multiple populations. RESULTS: We identified CDKN2A/B and four novel type 2 diabetes association signals with p < 1 × 10(-5) from the meta-analysis. Thirteen variants within these four loci were followed up in two independent Chinese cohorts, and rs10229583 at 7q32 was found to be associated with type 2 diabetes in a combined analysis of 11,067 cases and 7,929 controls (p meta = 2.6 × 10(-8); OR [95% CI] 1.18 [1.11, 1.25]). In silico replication revealed consistent associations across multiethnic groups, including five East Asian populations (p meta = 2.3 × 10(-10)) and a population of European descent (p = 8.6 × 10(-3)). The rs10229583 risk variant was associated with elevated fasting plasma glucose, impaired beta cell function in controls, and an earlier age at diagnosis for the cases. The novel variant lies within an islet-selective cluster of open regulatory elements. There was significant heterogeneity of effect between Han Chinese and individuals of European descent, Malaysians and Indians. CONCLUSIONS/INTERPRETATION: Our study identifies rs10229583 near PAX4 as a novel locus for type 2 diabetes in Chinese and other populations and provides new insights into the pathogenesis of type 2 diabetes.


Assuntos
Cromossomos Humanos Par 7 , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Proteínas de Homeodomínio/genética , Fatores de Transcrição Box Pareados/genética , Adulto , Idoso , Povo Asiático , China , Diabetes Mellitus Tipo 2/etnologia , Feminino , Marcadores Genéticos , Variação Genética , Genótipo , Hong Kong , Humanos , Células Secretoras de Insulina/citologia , Japão , Masculino , Pessoa de Meia-Idade , Singapura
20.
Allergy ; 68(2): 195-203, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23253152

RESUMO

BACKGROUND: Allergy is an acquired hypersensitivity reaction of the immune system mediated by cross-linking of allergen-specific IgE-bound high-affinity IgE receptors, leading to immediate mast cell degranulation. Artesunate is a semi-synthetic derivative of artemisinin, an active component of the medicinal plant Artemisia annua. Artesunate is a clinically effective anti-malarial drug and has recently been shown to attenuate allergic asthma in mouse models. This study investigated potential anti-allergic effects of artesunate in animal models of IgE-dependent anaphylaxis. METHODS: Anti-allergic actions of artesunate were evaluated in passive cutaneous anaphylaxis and passive systemic anaphylaxis mouse models, and in ovalbumin-induced contraction of bronchial rings isolated from sensitized guinea pigs. Direct mast cell-stabilizing effect of artesunate was examined in RBL-2H3 mast cell line and in mature human cultured mast cells. Anti-allergic signaling mechanisms of action of artesunate in mast cells were also investigated. RESULTS: Artesunate prevented IgE-mediated cutaneous vascular hyperpermeability, hypothermia, elevation in plasma histamine level, and tracheal tissue mast cell degranulation in mice in a dose-dependent manner. In addition, artesunate suppressed ovalbumin-mediated guinea pig bronchial smooth muscle contraction. Furthermore, artesunate concentration-dependently blocked IgE-mediated degranulation of RBL-2H3 mast cells and human culture mast cells. Artesunate was found to inhibit IgE-induced Syk and PLCγ1 phosphorylation, production of IP(3) , and rise in cytosolic Ca(+2) level in mast cells. CONCLUSIONS: We report here for the first time that artesunate possesses anti-allergic activity by blocking IgE-induced mast cell degranulation, providing a foundation for developing artesunate for the treatment of allergic asthma and other mast cell-mediated allergic disorders.


Assuntos
Anafilaxia/tratamento farmacológico , Antimaláricos/farmacologia , Artemisininas/farmacologia , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Anafilaxia/imunologia , Animais , Antialérgicos/farmacologia , Artesunato , Asma/tratamento farmacológico , Asma/imunologia , Asma/fisiopatologia , Degranulação Celular/imunologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Cobaias , Humanos , Imunidade Celular/fisiologia , Immunoblotting , Imunoglobulina E/imunologia , Imunoglobulina E/metabolismo , Técnicas In Vitro , Mastócitos/fisiologia , Camundongos , Distribuição Aleatória
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