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1.
Mol Oncol ; 16(11): 2274-2294, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35298869

RESUMO

Hepatocellular carcinoma (HCC) is characterized by rapid growth, early vascular invasion, and high metastasis. Currently available US Food and Drug Administration (FDA)-approved drugs show low therapeutic efficacy, limiting HCC treatment to chemotherapy. We designed and synthesized a novel small molecule, SCT-1015, that allosterically activated adenosine monophosphate-activated protein kinase (AMPK) to suppress the aerobic glycolysis in HCC. SCT-1015 was shown to bind the AMPK α and ß-subunit interface, thereby exposing the kinase α domain to the upstream kinases, resulting in the increased AMPK activity. SCT-1015 dramatically reduced HCC cell growth in vitro and tumor growth in vivo. We further found that AMPK formed protein complexes with hypoxia-inducible factor 1-alpha (HIF1α) and that SCT-1015-activated AMPK promoted hydroxylation of HIF1α (402P and 564P), resulting in HIF1α degradation by the ubiquitin-proteasome system. With declined HIF1α abundance, many glycolysis-related enzymes were downregulated, suppressing aerobic glycolysis, and promoting oxidative phosphorylation. These results indicated that SCT-1015 channeled HCC cells into an unfavorable metabolic status. Overall, we reported SCT-1015 as a direct activator of AMPK signaling that held therapeutic potential in HCC.


Assuntos
Proteínas Quinases Ativadas por AMP , Antineoplásicos , Carcinoma Hepatocelular , Glicólise , Neoplasias Hepáticas , Proteínas Quinases Ativadas por AMP/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/enzimologia , Linhagem Celular Tumoral , Ativação Enzimática , Glicólise/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/enzimologia , Transdução de Sinais
2.
Kaohsiung J Med Sci ; 28(11): 601-6, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23140768

RESUMO

This study investigated the incidence of retinopathy of prematurity (ROP) and its risk factors in a tertiary referral hospital in Taiwan to evaluate the applicability of the ROP screening guidelines published by the American Academy of Pediatrics, American Academy of Ophthalmology, and American Association for Pediatric Ophthalmology and Strabismus in 2006 (2006 guidelines). A pediatric ophthalmologist applied the 2006 guidelines to screen for ROP and to treat with laser photocoagulation in each case. We retrieved all records of premature infants referred for ROP screening at the hospital during 2004 to 2008. Univariate logistic regression analysis was applied firstly to identify factors correlating with stage 3 ROP or with laser treatment, and then those significant (p < 0.05) risk factors were analyzed by multivariate logistic regression. In the 138 male and 118 female premature infants in this study, mean gestation age was 30.8 ± 2.8 weeks, and mean birth weight was 1464.7 ± 434.2 g. The percentage of infants with ROP in at least one eye was 38.7%. Thirty two (12.5%) had ROP stage 3 or higher in at least one eye. Multivariate logistic regression analysis showed that the best predictors of type 1 pre-threshold ROP (requiring laser treatment) were young gestational age, low birth weight and male gender. As medical care of extremely premature infants improves, timely identification and treatment of conditions such as ROP are essential. Although the incidence of ROP in this institute was comparable to that in developing countries and higher than that in developed countries, the 2006 guidelines originally developed for a United States population were still applicable. However, the 2006 guidelines should be modified for a Taiwan population by considering gender.


Assuntos
Unidades de Terapia Intensiva Neonatal , Retinopatia da Prematuridade/diagnóstico , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Fotocoagulação a Laser , Triagem Neonatal/métodos , Guias de Prática Clínica como Assunto , Retinopatia da Prematuridade/cirurgia
3.
Pediatr Neonatol ; 53(4): 245-51, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22964282

RESUMO

BACKGROUND: In order to reduce the unnecessary use of and provide appropriate guidance for the administration of antibiotics, the neonatal bacterial infections screening score (NBISS) was developed to assess each new patient that is admitted to the neonatal intensive care unit (NICU). METHODS: NBISS was designed based on maternal risk factors, clinical presentations, and laboratory data. The total score of each new patient is calculated at the time of admission. The first period of this study was an observational survey. Receiver operating characteristic (ROC) curves were used to determine the best cut-off NBISS for the diagnosis of bacterial infection (BI) and guide the use of antibiotics during the second period of this study. RESULTS: Of 250 neonates who were admitted to the NICU, 237 (94.8%) received antibiotics during the first period of study. The initial total scores were not statistically different between the BI and non-BI groups (p = 0.155). We weighted C-reaction protein (CRP) (by 8×), the presence of a bulging fontanelle, pus from the ear canal, redness around the umbilicus, reduced movement, and being unable to feed (each by 5×) as significantly different between the BI and non-BI groups (p = 0.015). Weighted scores >8 points demonstrated the best diagnostic accuracy for indicating BI. After introducing NBISS for predicting BI in new patients admitted to NICU, the rate of antibiotic use significantly decreased from 94.8% to 60.3% between the two periods. CONCLUSION: Using this simple screening strategy, we were able to clinically reduce the use of unnecessary antibiotics.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Biomarcadores/análise , Proteína C-Reativa/análise , Feminino , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Masculino , Valor Preditivo dos Testes , Curva ROC , Fatores de Risco , Taiwan , Procedimentos Desnecessários
4.
Pediatr Neonatol ; 53(3): 178-83, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22770106

RESUMO

OBJECTIVE: To evaluate the effects on neonatal outcomes between very-low-birth-weight (VLBW) preterm newborns with and without maternal use of antenatal corticosteroids (ACS). METHODS: We retrospectively reviewed medical records of VLBW premature infants who were admitted to Kaohsiung Medical University Hospital between 1999 and 2008. A total of 256 infants were enrolled in this study. A total of 174 neonates did not receive any ACS, and 82 neonates received ACS. A total of 37 neonates received one dose of ACS, and 45 neonates received more than one dose of ACS, referred to as "multiple-dose ACS." In addition, these 82 infants were divided to betamethasone group (n=8) and dexamethasone group (n=50) with 24 infants excluded because of inadequate information. RESULTS: Neonates with multiple-dose ACS had lower incidence of surfactant use and lower rate of intubation than neonates without ACS. There were no differences in the occurrences of intraventricular hemorrhage, necrotizing enterocolitis, retinopathy of prematurity, sepsis, and chronic lung disease with one-dose vs. multiple-dose ACS and in the betamethasone group vs. the dexamethasone group. CONCLUSIONS: ACS reduces the need for exogenous surfactant, and the need for endotracheal tube insertion at birth in VLBW premature infants.


Assuntos
Corticosteroides/farmacologia , Feto/efeitos dos fármacos , Recém-Nascido de muito Baixo Peso , Feminino , Humanos , Recém-Nascido , Intubação Intratraqueal , Masculino , Surfactantes Pulmonares/uso terapêutico , Estudos Retrospectivos
5.
Kaohsiung J Med Sci ; 28(7): 390-6, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22726902

RESUMO

The objective of this study was to examine the impact of low birth weight and preterm birth on a toddler's inattention and development, including cognitive, language, motor, social-emotional and adaptive behaviors. A total of 105 toddlers enrolled for the study; they were divided into four groups: 40 full-term and normal birth weight (NBW, birth weight greater than 2500 g) toddlers, 24 moderate birth weight (MLBW, birth weight between 2499 and 1500 g) toddlers, 20 very to extremely low birth weight (V-ELBW, 12 between 1000 and 1499 g and 8 lower than 1000 g) toddlers, and 21 term toddlers who were recruited from a clinic of developmental delay as the developmental delay at risk (DDR) group. The Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III) and Disruptive Behavior Rating Scale-Toddler were used. The findings were as follows: (1) DDR group performed worst in BSID-III; (2) although there were no statistical differences among the NBW, MLBW, and V-ELBW groups in BSID-III, the lower the birth weight, the lower the average performance, especially in language, adaptive social behavior, and adaptive practical behavior; and (3) comparing the inattention score, the DDR group was the poorest, normal and V-ELBW groups were the best, and MLBW group was in the middle. In conclusion, low birth weight and preterm delivery affected children's inattention and development of language, adaptive social behavior, and adaptive practical behavior.


Assuntos
Recém-Nascido de Baixo Peso/crescimento & desenvolvimento , Recém-Nascido Prematuro/crescimento & desenvolvimento , Adaptação Psicológica , Análise de Variância , Atenção , Pré-Escolar , Cognição , Feminino , Humanos , Lactente , Recém-Nascido de Baixo Peso/psicologia , Recém-Nascido , Recém-Nascido Prematuro/psicologia , Desenvolvimento da Linguagem , Masculino , Nascimento Prematuro
6.
Early Hum Dev ; 88(8): 617-22, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22349187

RESUMO

BACKGROUND: A clear understanding of the factors associated with bone status in newborn infants is essential for devising strategies for preventing osteoporotic fracture in future generations. OBJECTIVE: The aims of this study were to perform bone speed of sound (SOS) to assess the status of the tibia in preterm and full-term newborns, and to evaluate factors associated with bone status at birth. STUDY DESIGNS: Bone SOS was measured by quantitative ultrasonography on the left tibia in full-term and preterm newborn infants immediately after birth. A birth chart and maternal history were recorded. Univariate and multivariate analyses were performed to identify factors affecting bone SOS at birth. SUBJECTS: The study analyzed 667 infants, including 370 males and 297 females, during study period. RESULTS: Univariate analysis revealed that gender, gestational age (GA) and birth anthropometrics significantly affected tibial bone SOS at birth whereas maternal factors did not. Multivariate multiple regression analysis revealed that gender (male-to-female coefficient of 45.71 and 32.52 in premature and full-term infants, respectively), GA (coefficient of 32.55 and 31.27 in premature and full-term infants, respectively, for every 1-week increase), and birth weight (coefficient of -0.11 and -0.103 in premature and full-term infants, respectively, for every 1-gram increase) were important factors affecting tibial bone SOS in both preterm and full-term newborn infants at birth. CONCLUSIONS: Male gender and advanced GA have a positive effect on increasing tibial bone SOS at birth, while birth weight had a negative effect on increasing tibial bone SOS. Tibial bone SOS is higher in small-for-gestational-age infants than in those of appropriate-for-gestational-age infants.


Assuntos
Recém-Nascido , Recém-Nascido Prematuro , Tíbia/diagnóstico por imagem , Peso ao Nascer , Densidade Óssea , Feminino , Idade Gestacional , Humanos , Recém-Nascido Pequeno para a Idade Gestacional , Masculino , Fatores Sexuais , Ultrassonografia
7.
J Trop Pediatr ; 57(2): 145-51, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21447596

RESUMO

BACKGROUND: Early diagnosis of serious bacterial infection (SBI) in young infants is a difficult problem by clinical symptoms and signs. The goal of this study is to evaluate the predictive value of plasma IP-10 levels for early diagnosis of SBI in young infants <4 months of age. METHODS: We enrolled pediatric patients who were <4 months of age with a clinical suspicion to have SBI admitted in neonatal intensive care unit or complete nursing unit of Pediatric Department of Kaohsiung Medical University Hospital. Blood was drawn for measurement of complete blood counts, C-reactive protein (CRP) and plasma IP-10 levels and microbiological cultures were obtained at the time of admission. RESULTS: There were 60 patients enrolled in this study. The SBI group (n = 21) have higher plasma IP-10 levels than those infants without SBI (n = 39) [median 104.8 (range 0-1457.1) versus 0 (range 0-129.3) pg ml(-1), P = 0.0161 after adjusting age]. A plasma IP-10 level >48.2 pg ml(-1) had the best diagnostic accuracy for indicating SBI {sensitivity 81.0% [95% confidence interval (CI) 71.1-90.1%]; specificity 94.9% [95% CI 65.4-87.0%]; positive likelihood ratio 15.9, negative likelihood ratio 0.2}. CONCLUSION: In infants who were <4 months of age with suspicion of SBI, IP-10 assay might be a good predictor. Key words: chemokine, IP-10, serious bacterial infection, young infant, C-reactive protein.


Assuntos
Infecções Bacterianas/diagnóstico , Proteína C-Reativa/análise , Quimiocina CXCL10/sangue , Infecções Bacterianas/sangue , Infecções Bacterianas/microbiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Hospitais Universitários , Humanos , Lactente , Recém-Nascido , Masculino , Valor Preditivo dos Testes , Curva ROC
8.
J Clin Nurs ; 19(23-24): 3307-13, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20946444

RESUMO

AIMS: The aim of this study is to evaluate the effectiveness of structured discharge education on maternal confidence and caring knowledge and the growth of premature newborns. BACKGROUND: Parents of premature newborns are usually confronted with great difficulties in caring for their babies after discharge. Building maternal confidence and caring knowledge can help mothers reduce such difficulties of caring for their babies after discharge from hospital. DESIGN: Randomised controlled trial. METHODS: Mothers with premature babies were randomly assigned into experimental (n=29) and control groups (n=30) at a medical centre in southern Taiwan. The mothers of both groups had received a questionnaire concerning maternal confidence and caring knowledge at pretest. After the pretest, a structured discharged education programme was provided to the mothers of the experimental group. The control group only received traditional discharge education. Mothers of experimental and control groups again received the questionnaire of maternal confidence and caring knowledge at the day before discharge and one month after discharge. At that time, the body height and body weight of newborns were measured and recorded. RESULTS: Maternal confidence and caring knowledge of mothers in the experimental group were significantly higher than those of the control group at the day before discharge; however, there were no significant differences between the two groups one month after discharge. Using repeated anova analysis, the time × group interaction was significant for maternal confidence and caring knowledge, indicating that the groups differed significantly in changes in maternal confidence and caring knowledge over the three time points. CONCLUSIONS: Structured discharge education on mothers could significantly increase maternal confidence and caring knowledge at the day before discharge. Furthermore, structured discharge education could significantly increase the percentage of growth on body height of premature newborns. RELEVANCE TO CLINICAL PRACTICE: The results could help clinical nurses design appropriate discharge education programmes for mothers of premature newborns.


Assuntos
Cuidado do Lactente/métodos , Recém-Nascido Prematuro , Relações Mãe-Filho , Mães/educação , Alta do Paciente , Educação de Pacientes como Assunto , Adulto , Análise de Variância , Distribuição de Qui-Quadrado , Humanos , Cuidado do Lactente/psicologia , Recém-Nascido , Mães/psicologia , Inquéritos e Questionários , Taiwan
9.
J Paediatr Child Health ; 46(11): 653-9, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20796178

RESUMO

AIM: To evaluate whether assisted exercise could prevent the development of osteopenia of prematurity, we performed assisted exercise in the study group of very low birthweight (VLBW) premature infants. METHODS: Sixteen premature infants with birthweight below 1500 g were enrolled in this study and randomly assigned into the exercise (n = 8) and control (n = 8) groups. Assisted exercise involved full extension and flexion range of motion of the upper and lower extremities by a trained nurse with a schedule of 5 days a week for a total of 4 weeks. Bone strength was determined by quantitative ultrasound measurement of tibial bone speed of sound every 2 weeks during the study period. RESULTS: No difference in gender, birthweight, and gestation age between the exercise and control groups was noted. There was statistically significant less tibial bone speed of sound decrease in the exercise group on the sixth and eighth week of life. During the study period, there were no statistically significant differences in blood biochemistry data, including calcium, phosphorus, magnesium, alkaline phosphatase, osteocalcin and osteoprotegerin, between the two groups. CONCLUSIONS: This study revealed that early assisted exercise could improve bone strength in very low birthweight infants. The biochemical markers of bone metabolism, osteocalcin and osteoprotegerin, could not be the indicators for early diagnosis of osteopenia of prematurity.


Assuntos
Densidade Óssea/fisiologia , Doenças Ósseas Metabólicas/prevenção & controle , Terapia por Exercício , Recém-Nascido de muito Baixo Peso/fisiologia , Doenças Ósseas Metabólicas/diagnóstico por imagem , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/terapia , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/metabolismo , Feminino , Humanos , Recém-Nascido , Masculino , Taiwan , Ultrassonografia
11.
Pediatr Allergy Immunol ; 21(7): 1064-71, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20609134

RESUMO

Asthma is a complex disorder, which is known to be affected by interactions between genetic and environmental factors. The aim of this study was to investigate the three microsatellite polymorphisms of GT repeats in intron 2, AAT repeats in intron 20, and CA repeats in exon 29 of the NOS1 gene in 155 asthmatic children and 301 control children, and the interaction with environmental factors in southern Taiwan. Total serum IgE, phadiatop test and genetic polymorphisms were measured. The genotype frequency of 14/14-AAT repeats of the NOS1 gene was significantly higher in the asthmatic group (p = 0.01). Total IgE concentrations were higher in asthmatic children (p = 0.015) carrying the NOS1 14/14-AAT genotype than in subjects with other polymorphisms. The gene and environmental interaction effects were 3.83-fold, 6.86-fold, and 8.04-fold (all corrected p-values <0.001) between subjects carrying at least one NOS1 14-AAT allele and exposure to cockroaches, high levels of total IgE, and positive response against the phadiatop test in asthmatic children. The findings of this study provide strong evidence that NOS1 gene with 14-AAT tandem repeats has a significant effect in asthmatic children. Environmental factors and atopic status will enhance the asthmatic risk for children who carry NOS1 susceptible allele.


Assuntos
Asma/epidemiologia , Asma/genética , Óxido Nítrico Sintase Tipo I/genética , Asma/sangue , Asma/fisiopatologia , Criança , Análise Mutacional de DNA , Exposição Ambiental/efeitos adversos , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Imunoglobulina E/sangue , Masculino , Polimorfismo Genético , Fatores de Risco , Taiwan
12.
J Pediatr ; 157(1): 79-84, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20227723

RESUMO

OBJECTIVES: To determine whether B-type natriuretic peptide (BNP) predicts indomethacin responsiveness in premature neonates with patent ductus arteriosus (PDA). STUDY DESIGN: Premature neonates receiving indomethacin for an echocardiograhically large (diameter>1.5 mm) and clinically significant PDA were prospectively studied. All neonates underwent paired echocardiography and BNP measurements at baseline and 24 hours after each dose of indomethacin. After treatment, neonates who responded (with closed or insignificant PDA) and neonates who did not respond (with persistent significant PDA requiring surgical ligation) were compared. RESULTS: Thirty-one premature neonates (mean gestational age, 30 weeks) underwent 119 paired echocardiography and BNP determinations. Mean BNP levels (1286+/-986 pg/mL) associated with significant PDA (n=96) were higher than those associated with closed or insignificant PDA (n=23; 118+/-124 pg/mL; P<.001). Twenty-three neonates responded and 8 neonates did not respond to indomethacin. Mean baseline BNP levels were higher in neonates who were non-responders (2234+/-991 pg/mL) than neonates who were responders (983+/-814 pg/mL; P=.001). A baseline BNP level>1805 pg/mL had a sensitivity rate of 88% and a specificity rate of 87% for predicting indomethacin non-responsiveness (P=.003). CONCLUSIONS: High baseline BNP levels predict poor responses to indomethacin and the need for surgery in premature neonates with PDA.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Permeabilidade do Canal Arterial/tratamento farmacológico , Indometacina/uso terapêutico , Recém-Nascido Prematuro , Peptídeo Natriurético Encefálico/sangue , Fármacos Cardiovasculares/administração & dosagem , Inibidores de Ciclo-Oxigenase/administração & dosagem , Permeabilidade do Canal Arterial/sangue , Permeabilidade do Canal Arterial/diagnóstico por imagem , Feminino , Idade Gestacional , Humanos , Indometacina/administração & dosagem , Recém-Nascido , Recém-Nascido Prematuro/sangue , Masculino , Valor Preditivo dos Testes , Gravidez , Índice de Gravidade de Doença , Resultado do Tratamento , Ultrassonografia
13.
Pediatr Neonatol ; 51(1): 31-6, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20225536

RESUMO

BACKGROUND: Cytokines and chemokines play important roles in asthma. However, little information exists on the effects of inhaled corticosteroids on cytokine and chemokine plasma levels in childhood asthma. We compared the pharmaceutical effects of two inhaled corticosteroids used in pediatric patients with mild-to-moderate asthma, budesonide and fluticasone propionate. METHODS: Pediatric patients aged 5-18 years old were enrolled in this randomized, open-label, observer-blinded study and received 3 months of treatment with either inhaled budesonide (200 microg/puff) or fluticasone propionate (250 microg/puff), at two puffs per day. Peak expiratory flow (PEF), exhaled nitric oxide, Asthma Control Test (ACT), plasma Levels of tumor necrosis factor-alpha, thymus and activation-regulated chemokine, and interferon-inducible protein 10 were measured before treatment and monthly for 3 months after treatment. RESULTS: There were six patients in the budesonide group, and eight in the fluticasone group. After 3 months, both groups showed improved PEF. In the first month, PEF improved more in the budesonide group than in the fluticasone group, though the difference was not significant. After treatment, ACT scores in both groups were well controlled, except for one patient in the fluticasone group. The fluticasone group had a more significant reduction in exhaled nitric oxide than the budesonide group in the first month. CONCLUSION: Improvements in lung function were more rapid in the budesonide group than the fluticasone group. However, patients in the fluticasone group had better anti-inflammatory responses than those in the budesonide group. We conclude that each inhaled corticosteroids have its own clinical and laboratory effects.


Assuntos
Androstadienos/uso terapêutico , Asma/tratamento farmacológico , Budesonida/uso terapêutico , Adolescente , Asma/imunologia , Asma/fisiopatologia , Testes Respiratórios , Quimiocina CCL17/sangue , Quimiocina CXCL10/sangue , Criança , Pré-Escolar , Feminino , Fluticasona , Humanos , Pulmão/fisiopatologia , Masculino , Óxido Nítrico/metabolismo , Fator de Necrose Tumoral alfa/sangue
14.
J Med Food ; 13(2): 391-8, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20170340

RESUMO

Dietary flavonoids have various biological functions, and there is increasing evidence that reduced prevalence and severity of allergic reactions are associated with the intake of flavonoids. Among natural flavonoids, apigenin is a potent anti-inflammatory agent. However, the mechanisms of apigenin's effect remain uncertain. Monocyte-derived chemokine (MDC) plays a pivotal role in recruiting T-helper (Th) 2 cells in the allergic inflammation process. In the late phase of allergic inflammation, the Th1 chemokine interferon-inducible protein 10 (IP-10) has also been found in elevated levels in the bronchial alveolar fluid of asthmatic children. We used human THP-1 monocyte cells, pretreated with or without apigenin, prior to lipopolysaccharide stimulation. By means of enzyme-linked immunosorbent assay, we found that apigenin inhibited production of both MDC and IP-10 by THP-1 cells and that the suppressive effect of apigenin was not reversed by the estrogen receptor antagonist ICI182780. The p65 phosphorylation of nuclear factor kappaB remained unaffected, but the phosphorylation of p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinase mitogen-activated protein kinase pathways were all blocked. We found that inhibition of c-raf phosphorylation might be the target of apigenin's anti-inflammation property.


Assuntos
Anti-Inflamatórios/farmacologia , Apigenina/farmacologia , Quimiocina CXCL10/metabolismo , Quimiocinas/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Monócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Bronquíolos/metabolismo , Líquido da Lavagem Broncoalveolar , Ensaio de Imunoadsorção Enzimática , Antagonistas de Estrogênios/metabolismo , Humanos , Hipersensibilidade/complicações , Inflamação/etiologia , Inflamação/metabolismo , Lipopolissacarídeos , Monócitos/metabolismo , NF-kappa B/metabolismo , Fenantrenos , Fosforilação , Proteínas Proto-Oncogênicas c-raf/metabolismo , Receptores de Estrogênio/metabolismo , Células Th1/metabolismo , Células Th2/metabolismo , eIF-2 Quinase/metabolismo
15.
Kaohsiung J Med Sci ; 25(12): 633-9, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19951848

RESUMO

Early diagnosis of serious bacterial infections (SBI) in febrile young infants based on clinical symptoms and signs is difficult. This study aimed to evaluate the diagnostic values of circulating chemokines and C-reactive protein (CRP) levels in febrile young infants < 3 months of age with suspected SBI. We enrolled 43 febrile young infants < 3 months of age with clinically suspected SBI who were admitted to the neonatal intensive care unit or complete nursing unit of the pediatric department of Kaohsiung Medical University Hospital between December 2006 and July 2007. Blood was drawn from the patients at admission, and complete blood counts, plasma levels of CRP, granulocyte colony-stimulating factor (G-CSF), and chemokines, including interleukin-8 (IL-8), macrophage inflammatory protein-1alpha, macrophage inflammatory protein-1beta, monokine induced by interferon-gamma, and monocyte chemotactic protein-1 were measured. Patients symptoms and signs, length of hospital stay, main diagnosis, and results of routine blood tests and microbiological culture results were recorded. Twenty-six infants (60.5%) were diagnosed with SBI, while 17 (39.5%) had no evidence of SBI based on the results of bacterial cultures. CRP, IL-8 and G-CSF levels were significantly higher in the infants with SBI than in those without SBI Plasma levels of other chemokines were not significantly different between the groups. The area under the receiver-operating characteristic (ROC) curve for differentiating between the presence and absence of SBI was 0.79 for CRP level. Diagnostic accuracy was further improved by combining CRP and IL-8, when the area under the ROC curve increased to 0.91. CRP levels were superior to IL-8 and G-CSF levels for predicting SBI in febrile infants at initial survey. IL-8 levels could be used as an additional diagnostic tool in the initial evaluation of febrile young infants, allowing clinicians to treat these patients more appropriately.


Assuntos
Infecções Bacterianas/sangue , Quimiocinas/sangue , Febre/sangue , Proteína C-Reativa/análise , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Curva ROC
16.
Pediatr Neonatol ; 50(5): 202-7, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19856863

RESUMO

BACKGROUND: One of the most common complications in infants under parenteral nutrition treatment is parenteral nutrition-associated cholestasis (PNAC). The etiology of PNAC is thought to be multifactorial. The aims of this study were to evaluate the risk factors for PNAC in our neonatal intensive care unit and determine useful predictors. METHODS: This study enrolled premature infants (gestational age <36 weeks) who were admitted to our neonatal intensive care unit and treated with parenteral nutrition infusion for at least 2 weeks between January 2004 and January 2007. Multiple possible risk factors were analyzed by a retrospective review study design. PNAC was defined as direct bilirubin greater than 1.5 mg/dL during parenteral nutrition. RESULTS: A total of 62 premature infants with prolonged course of parenteral nutrition were eligible for this study; 11 (17.74%) of the infants developed PNAC. There were significant differences in terms of gestational age, birth body weight, duration of parenteral nutrition, septic episodes, and average energy intake during the 2nd and 3rd weeks of life between infants with cholestasis and those without cholestasis. Of these risk factors, the duration of parenteral nutrition was most significant after multivariate logistic regression analysis. CONCLUSION: Young gestational age, low birth body weight, more sepsis episodes, and long duration of parenteral nutrition were significant risk factors for PNAC in our study. Low energy intake during the 2nd and 3rd weeks of life is a predictor for PNAC.


Assuntos
Colestase/etiologia , Nutrição Parenteral/efeitos adversos , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Modelos Logísticos , Masculino , Estudos Retrospectivos , Fatores de Risco , Sepse/etiologia
17.
Cell Biol Int ; 33(12): 1230-6, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19732845

RESUMO

Calotropin is one of cardenolides isolated from milkweed used for medicinal purposes in many Asian countries. Whereas calotropin possesses cytotoxicity against several cancer cells, the mechanisms of action remain unclear. We set out to evaluate the cytotoxic mechanism of calotropin on human chronic myeloid leukemia K562 cells. Calotropin inhibited the growth of K562 cells in a time- and dose-dependent manner by G(2)/M phase arrest. It upregulated the expression of p27 leading to this arrest by downregulating the G2/M regulatory proteins, cyclins A and B, and by upregulating the cdk inhibitor, p27. Furthermore, it downregulated anti-apoptotic signaling (XIAP and survivin) and survival pathways (p-Akt and NFkappaB), leading to caspase-3 activation which resulted in the induction of apoptosis. In all, calotropin exerted its anticancer activity on K562 cells by modulating the pro-survival signaling that leads to induction of apoptosis.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Asclepias , Cardenolídeos/farmacologia , Caspases/metabolismo , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Cardenolídeos/isolamento & purificação , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Células HL-60 , Humanos , Células K562
18.
Pediatr Neonatol ; 50(3): 110-6, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19579757

RESUMO

BACKGROUND: Multiple packed red blood cell (PRBC) transfusions in very low birth weight (VLBW) prematurity have been suggested to be a risk factor for the development of retinopathy of prematurity (ROP) or for chronic lung disease (CLD). The purpose of this study was to examine the effect of PRBC transfusions on the outcome of VLBW prematurity. METHODS: In total, between July 2005 and June 2006, 36 VLBW preterm babies were admitted to our neonatal intensive care unit and were randomly allocated to the "restrictive" (n= 19) or "liberal" (n= 17) criteria for PRBC transfusion. Complete blood count (CBC) was examined at admission and 30 days later. Reticulocyte counts, serum iron and ferritin were examined and compared with the clinical outcomes. RESULTS: Infants in the liberal group received a larger PRBC transfusion volume compared with the restrictive group over 30 days (41.7+/-20.1 vs. 27.2+/-15.9mL, p=0.029). There were no significant differences in the proportion of patients with respiratory distress syndrome, patent ductus arteriosus, severe intraventricular hemorrhage, ROP or CLD between the two groups. The laboratory data, except reticulocyte count, showed no significant difference on day 30. Further analysis of premature babies with and without CLD showed that total transfused blood volume greater than 30mL over 30 days was a risk factor for developing CLD in VLBW infants. CONCLUSION: Both criteria of PRBC transfusion had similar clinical outcomes, although liberal transfusion resulted in a greater amount of blood transfused and a low reticulocyte count at 30 days of age. We suggest restrictive criteria for minimizing the overall amount of transfusion to less than 30 mL may be a better way of preventing CLD in VLBW infants.


Assuntos
Transfusão de Sangue/métodos , Cuidados Críticos/métodos , Doenças do Prematuro/prevenção & controle , Volume Sanguíneo , Doença Crônica , Protocolos Clínicos , Hematócrito , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/sangue , Recém-Nascido de muito Baixo Peso , Pneumopatias/sangue , Pneumopatias/prevenção & controle , Masculino , Avaliação de Resultados em Cuidados de Saúde
19.
Pediatr Pulmonol ; 44(5): 472-9, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19360851

RESUMO

BACKGROUND: The prevalence of obesity and asthma has increased in recent decades. We investigated the relationship between body mass index (BMI) and lung function, and also tried to determine if asthma prevalence differs between obese and non-obese children. METHODS: An International Study of Asthma and Allergies in Childhood (ISAAC) video questionnaire survey that included 170,457 students in junior high school was conducted during a 1-year period. Using random selection, 15,761 students were selected for lung function testing; 14,654 (93.0%) completed the lung function tests. Multiple logistic regression analysis was used to analyze the risk factor of asthma, such as atopic diathesis, BMI, exercise habits, smoking and secondary smoking. The detailed comparison in lung functions was plotted by asthmatic versus non-asthmatic, and between both sexes. RESULTS: The risk factor of ISAAC-identified asthma were male sex, atopy, elevated BMI, higher education levels of the parents (higher than senior high school), family smoking >or=1 pack/day, self-reported smoking. The prevalence of asthma increased as BMI elevated in both sex. The FEV1/FVC declined as BMI elevated in both sex. The thin and underweight male students had declined FEF 25-75% and PEF. CONCLUSIONS: Extreme BMI is associated with different lung function impairment. This study showed that high BMI in both sexes was associated with low FEV1/FVC and low BMI in males are associated with poor PEF and FEF 25-75% and contributed to the symptoms of asthma.


Assuntos
Asma/complicações , Obesidade/complicações , Adolescente , Asma/epidemiologia , Índice de Massa Corporal , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Modelos Logísticos , Masculino , Obesidade/epidemiologia , Razão de Chances , Prevalência , Testes de Função Respiratória , Fatores de Risco , Fatores Sexuais , Fumar , Taiwan/epidemiologia , Poluição por Fumaça de Tabaco
20.
J Trop Pediatr ; 55(2): 103-8, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18952629

RESUMO

BACKGROUND: Early diagnosis of serious bacterial infection (SBI) in young infants is a difficult problem by clinical symptoms and signs. The goal of this study is to evaluate the predictive value of plasma IP-10 levels for early diagnosis of SBI in young infants <4 months of age. METHODS: We enrolled pediatric patients who were <4 months of age with a clinical suspicion to have SBI admitted in neonatal intensive care unit or complete nursing unit of Pediatric Department of Kaohsiung Medical University Hospital. Blood was drawn for measurement of complete blood counts, C-reactive protein (CRP) and plasma IP-10 levels and microbiological cultures were obtained at the time of admission. RESULTS: There were 60 patients enrolled in this study. The SBI group (n = 21) have higher plasma IP-10 levels than those infants without SBI (n = 39) [median 104.8 (range 0-1457.1) versus 0 (range 0-129.3) ng ml(-1), P = 0.0161 after adjusting age]. A plasma IP-10 level >48.2 ng ml(-1) had the best diagnostic accuracy for indicating SBI [sensitivity 81.0% [95% confidence interval (CI) 71.1-90.1%]; specificity 94.9% [95% CI 65.4-87.0%]; positive likelihood ratio 15.9, negative likelihood ratio 0.2}. CONCLUSION: In infants who were <4 months of age with suspicion of SBI, IP-10 assay might be a good predictor.


Assuntos
Infecções Bacterianas/diagnóstico , Proteína C-Reativa/análise , Quimiocina CXCL10/sangue , Infecções Bacterianas/sangue , Infecções Bacterianas/microbiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Hospitais Universitários , Humanos , Lactente , Recém-Nascido , Masculino , Valor Preditivo dos Testes , Curva ROC
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