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2.
J Formos Med Assoc ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34535376

RESUMO

BACKGROUND/PURPOSE: Identifying child abuse is sometimes challenging due to its various presentations. To facilitate timely identification of critical or complex cases of physical abuse outside our child protection center, we established an outreach multidisciplinary team (OMDT) to support Kaohsiung City Government in 2014. The objective of this study was to describe our experience of OMDT services during a 6-year period and examine its role in assisting law enforcement. METHODS: We retrospectively analyzed all OMDT cases from January 2014 to January 2020. Clinical characteristics and OMDT reports were reviewed. After inspection by our OMDT, cases were determined as indicating either a high risk or low risk of child abuse. Associations among clinical characteristics, radiographic findings, OMDT decisions and case outcomes including law enforcement and prosecution were examined. RESULTS: Thirty-two cases (22 [68.8%] males and 10 [31.2%] females; mean age 24.2 months) received OMDT service, of whom 28 (87.5%) were admitted to the pediatric intensive care unit. The victims had an average of 2.2 types of wounds in 3.4 locations. The most common finding on radiography was subdural hemorrhage (18, 56.3%), followed by subarachnoid hemorrhage (31, 31.3%). Law enforcement was activated in 20 (64.5%) cases, and was only associated with the high-risk group as determined by the OMDT (p < 0.05) but not with any other variables. CONCLUSION: Our experience indicates that an OMDT can play an important role in child protection and activating law enforcement for children with complex or critical physical abuse. We suggest that in Taiwan, OMDT services should be incorporated into child protection centers, National Health Insurance system and governmental child protection policies.

4.
Int J Mol Sci ; 22(6)2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33810164

RESUMO

The ductus arteriosus (DA) is a physiologic vessel crucial for fetal circulation. As a major regulating factor, the prostaglandin pathway has long been the target for DA patency maintenance or closure. However, the adverse effect of prostaglandins and their inhibitors has been a major unsolved clinical problem. Furthermore, a significant portion of patients with patent DA fail to respond to cyclooxygenase inhibitors that target the prostaglandin pathway. These unresponsive medical patients ultimately require surgical intervention and highlight the importance of exploring pathways independent from this well-recognized prostaglandin pathway. The clinical limitations of prostaglandin-targeting therapeutics prompted us to investigate molecules beyond the prostaglandin pathway. Thus, this article introduces molecules independent from the prostaglandin pathway based on their correlating mechanisms contributing to vascular remodeling. These molecules may serve as potential targets for future DA patency clinical management.


Assuntos
Canal Arterial/metabolismo , Canal Arterial/patologia , Remodelação Vascular , Animais , Biomarcadores , Movimento Celular , Proliferação de Células , Canal Arterial/embriologia , Permeabilidade do Canal Arterial/etiologia , Permeabilidade do Canal Arterial/metabolismo , Matriz Extracelular , Humanos , Miócitos de Músculo Liso/metabolismo , Prostaglandinas/metabolismo , Transdução de Sinais , Remodelação Vascular/genética
5.
Oral Dis ; 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33655573

RESUMO

OBJECTIVES: The myeloid-derived suppressor cells (MDSCs) frequently have a high expansion in cancer patients. This research explored whether administration of ß-glucan could increase anti-tumor immunity in oral squamous cell carcinoma (OSCC) patients. MATERIALS AND METHODS: This study evaluated the MDSC level of circulating blood as CD33+ /CD11b+ /HLA-DR-/low by flow cytometry in 30 healthy donors (HDs, group I), in 48 oral squamous cell carcinoma (OSCC) patients before and after 14-day preoperative administration of ß-glucan (group II), and in 52 OSCC patients without taking ß-glucan (group III). RESULTS: A significantly higher mean MDSC level was observed in 100 OSCC patients than in 30 HDs (p < .001). There was a significant reduction of the mean MDSC level in group II patients after taking ß-glucan (p < .001). Moreover, we discovered a significantly higher recurrence-free survival (RFS) in group II than in group III patients (p = .026). Finally, the multivariate Cox regression further identified the MDSC level ≤1% and administration of ß-glucan as more favorable prognostic factors for OSCC patients. CONCLUSION: Preoperative administration of ß-glucan can augment anti-tumor immunity and increase RFS rate via subversion of suppressive function of MDSC in OSCC patients.

6.
Neurourol Urodyn ; 40(3): 763-770, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33604897

RESUMO

AIMS: Interstitial cystitis (IC) is a chronic pain syndrome that is characterized by suprapubic pain upon bladder filling. Bletilla striata, a well-known traditional Chinese herb with established efficacy in wound healing and anti-inflammation, was hypothesized to improve the symptoms of IC possibly though forming a physical barrier that could isolate the bladder tissue from irritants. This study was conducted to evaluate the beneficial effects of intravesical treatment with B. striata extract solution (BSES) on visceral pain and bladder function of rats with zymosan-induced IC. METHODS: Thirty female rats were randomly divided into control group, zymosan-induced cystitis rats treated with normal saline (Z + NS), and zymosan-induced cystitis rats treated with BSES (Z + BSES). All rats underwent evaluation for abdominal withdrawal reflex (AWR) scores to assess visceral hypersensitivity, cystometrography, and electromyogram (EMG) of both external urethral sphincter and bladder detrusor. Data were analyzed by one way analysis of variance. RESULTS: The Z + NS group had an increased visceral hypersensitivity as compared to control group. Rats treated with BSES (Z + BSES group) had decreased AWR scores and amplitude of bladder detrusor-EMG. Besides, BSES treatment improved overactive bladder with significant effects on the extend of micturition interval and increase of storage of urine. CONCLUSIONS: Intravesical instillation of BSES can significantly alleviate zymosan-induced visceral hypersensitivity and bladder overactivity associated with IC. This study suggested that intravesical instillation with BSES might be a promising treatment for IC.


Assuntos
Cistite Intersticial/induzido quimicamente , Cistite Intersticial/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Polissacarídeos/uso terapêutico , Zimosan/efeitos adversos , Animais , Feminino , Polissacarídeos/farmacologia , Ratos , Ratos Sprague-Dawley
7.
Int J Med Sci ; 17(16): 2594-2602, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029102

RESUMO

Pulmonary hypertension (PH) is a lethal and rapidly progressing disorder if left untreated, but there is still no definitive therapy. An imbalance between vasoconstriction and vasodilation has been proposed as the mechanism underlying PH. Among the vasomediators of the pulmonary circulation is the renin-angiotensin system (RAS), the involvement of which in the development of PH has been proposed. Within the RAS, angiotensin-converting enzyme 2 (ACE2), which converts angiotensin (Ang) II into Ang-(1-7), is an important regulator of blood pressure, and has been implicated in cardiovascular disease and PH. In this study, we investigated the effects of the ACE2 activator diminazene aceturate (DIZE) on the development of PH secondary to left ventricular dysfunction. A model of PH secondary to left ventricular dysfunction was established in 6-week-old Wistar rats by ascending aortic banding for 42 days. The hemodynamics and pulmonary expression of ACE, Ang II, ACE2, Ang-(1-7), and the Ang-(1-7) MAS receptor were investigated in the early treatment group, which was administered DIZE (15 mg/kg/day) from days 1 to 42, and in the late treatment group, administered DIZE (15 mg/kg/day) from days 29 to 42. Sham-operated rats served as controls. DIZE ameliorated mean pulmonary artery pressure, pulmonary arteriolar remodeling, and plasma brain natriuretic peptide levels, in addition to reversing the overexpression of ACE and up-regulation of both Ang-(1-7) and MAS, in the early and late treatment groups. DIZE has therapeutic potential for preventing the development of PH secondary to left ventricular dysfunction through ACEII activation and the positive feedback of ANG-(1-7) on the MAS receptor. A translational study in humans is needed to substantiate these findings.

8.
Biomed Pharmacother ; 128: 110370, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32521457

RESUMO

We have recently shown that exogenous administration of extracellular heat shock protein HSC70, a previously recognized intracellular chaperone protein, can protect against LPS-induced cardiac dysfunction through anti-inflammatory actions. However, whether it can also exert anti-hypertrophic effect is unknown. The present study was aimed to investigate the efficacy of HSC70 against cardiac hypertrophy and its underlying molecular mechanisms. Cardiomyocytes were isolated from the cardiac ventricles of neonatal Wistar rats and LPS (1 µg/mL) was used to induce the hypertrophic responses. We found that HSC70 (0.1, 1 and 5 µg/mL) pretreatment attenuated LPS-induced cardiomyocyte hypertrophy dose-dependently. In addition, HSC70 mitigated LPS-induced inflammatory mediators including TNF-α, IL-6, NO, iNOS and COX-2, with down-regulated protein expression of MMP-2 and MMP-9. Moreover, HSC70 repressed LPS-induced signaling of MAPK and Akt. Finally, HSC70 inhibited NF-κB subunit p65, and the DNA binding activity of NF-κB. Taken together, these findings suggest that in vitro HSC70 can exert anti-hypertrophic effects through inhibition of pro-inflammatory mediators, which are potential mediated by the down-regulation of MAPK, Akt and NF-κB signaling pathways. In conclusion, extracellular HSC70 may be a novel pharmacologic strategy in the management of cardiac hypertrophy.


Assuntos
Anti-Inflamatórios/farmacologia , Cardiomegalia/prevenção & controle , Proteínas de Choque Térmico HSC70/farmacologia , Lipopolissacarídeos/toxicidade , Miócitos Cardíacos/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Cardiomegalia/induzido quimicamente , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Células Cultivadas , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Wistar , Proteínas Recombinantes/farmacologia , Fator de Transcrição RelA/metabolismo
9.
Ther Adv Respir Dis ; 13: 1753466619875928, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31544581

RESUMO

BACKGROUND: To determine the effectiveness of combined noninvasive ventilation (NIV) and mechanical insufflator-exsufflator (MI-E) for acute respiratory failure (ARF) in patients with neuromuscular disease (NMD), and outcome predictors. METHODS: A prospectively observational study of patients with ARF was conducted in a pediatric intensive care unit (PICU). All received combined NIV/MI-E during PICU stays between 2007 and 2017. Pertinent clinical variables of heart rate (HR), respiratory rate (RR), pH, PaCO2, and PaO2/FiO2 ratio were collected at baseline and at 2 h, 4-8 h, and 12-24 h after initiating use of NIV/MI-E. Treatment success was defined as avoiding intubation. RESULTS: A total of 62 ARF episodes in 56 patients with NMD (median age, 13 years) were enrolled. The most frequent underlying NMD was spinal muscular atrophy (32/62, 52%). ARF was primarily due to pneumonia (65%). The treatment success rate was 86%. PICU stay and hospitalization were shorter in the success group (9.4 ± 6.1 vs. 21.9 ± 13.9 days and 16.3 ± 7.8 vs. 33.6 ± 17.9 days, respectively; both p < 0.05). HR, RR, pH, and PaCO2 showed a progressive improvement, particularly after 4 h following successful NIV/MI-E treatment. RR decrease at 4 h, and pH increase and PaCO2 decrease at 4-8 h might predict success of NIV/MI-E treatment. The multivariate analysis identified PaCO2 at 4-8 h of 58.0 mmHg as an outcome predictor of NIV/MI-E treatment. CONCLUSIONS: Applying combined NIV/MI-E in the acute care setting is an efficient means of averting intubation in NMD patients with ARF. Clinical features within 8 h of the institution may predict treatment outcome. The reviews of this paper are available via the supplemental material section.


Assuntos
Insuflação , Pulmão/fisiopatologia , Doenças Neuromusculares/complicações , Ventilação não Invasiva , Insuficiência Respiratória/terapia , Doença Aguda , Adolescente , Adulto , Criança , Pré-Escolar , Terapia Combinada , Feminino , Humanos , Lactente , Insuflação/efeitos adversos , Unidades de Terapia Intensiva Pediátrica , Tempo de Internação , Masculino , Doenças Neuromusculares/diagnóstico , Doenças Neuromusculares/fisiopatologia , Ventilação não Invasiva/efeitos adversos , Estudos Prospectivos , Recuperação de Função Fisiológica , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
11.
Pediatr Neonatol ; 59(6): 543-552, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29706362

RESUMO

Kawasaki disease (KD) has become the most common form of pediatric systemic vasculitis. Although patients with KD received intravenous immunoglobulin (IVIG) therapy, coronary arterial lesions (CALs) still occurred in 5%-10% of these patients during the acute stage. CALs may persist and even progress to stenosis or obstruction. Therefore, CALs following KD are currently the leading cause of acquired heart diseases in children. The etiology of CALs remains unknown despite more than four decades of research. Two unsolved problems are IVIG unresponsiveness and the diagnosis of incomplete KD. The two subgroups of KD patients with these problems have a high risk of CAL. In April 2017, the American Heart Association (AHA) updated the guidelines for the diagnosis, treatment, and long-term management of KD. Compared with the previous KD guidelines published in 2004, the new guidelines provide solutions to the aforementioned two problems and emphasize risk stratification by using coronary artery Z score systems, as well as coronary severity-based management and long-term follow-up. Therefore, in this study, we merged the AHA Scientific Statement in 2017 with recent findings for Taiwanese KD patients to provide potential future care directions for Taiwanese patients with KD.


Assuntos
Síndrome de Linfonodos Mucocutâneos/terapia , Anti-Inflamatórios não Esteroides/uso terapêutico , Vasos Coronários/diagnóstico por imagem , Ecocardiografia , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Guias de Prática Clínica como Assunto
12.
Oral Oncol ; 75: 169-177, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29224816

RESUMO

OBJECTIVE: This study assessed whether hypermethylated ZNF582 and PAX1 genes in oral scrapings are correlated with the progression and prognosis of oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Methylation levels of ZNF582 and PAX1 genes in oral scrapings, collected from the cancer and adjacent normal oral mucosal sites of 80 OSCC patients before surgical cancer excision, were quantified using real-time methylation-specific PCR after bisulfite conversion. RESULTS: Both the mean methylation (M)-indices of ZNF582 and PAX1 genes in oral scrapings were significantly higher at the cancer sites than at the adjacent normal oral mucosal sites (both P < .001). In the oral scrapings collected from the adjacent normal oral mucosal sites, the higher M-index of methylated ZNF582 (ZNF582m) was significantly correlated with a more advanced clinical stage (P = .04). Moreover, the higher M-index of methylated PAX1 (PAX1m) was significantly related to larger tumor size (P = .046). When the 80 OSCC patients were classified based on gene methylation tests, using the oral scrapings collected from the adjacent normal oral mucosal sites, we found a significantly shorter 3-year overall survival in ZNF582m-positive, PAX1m-positive, and ZNF582m/PAX1m-positive OSCC patients than in ZNF582m-negative (P = .02), PAX1m-negative (P = .04), and ZNF582m/PAX1m-negative OSCC patients (P = .02), respectively. Multivariate Cox regression analyses identified ZNF582m and ZNF582m/PAX1m as independent unfavorable prognostic factors. CONCLUSION: Hypermethylated ZNF582 and PAX1 genes in the oral scrapings collected from adjacent normal oral mucosal sites rather than cancer sites are associated with aggressive progression and poor prognosis of OSCC.


Assuntos
Metilação de DNA , Fatores de Transcrição Kruppel-Like/genética , Mucosa Bucal/metabolismo , Neoplasias Bucais/patologia , Fatores de Transcrição Box Pareados/genética , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Neoplasias Bucais/genética , Prognóstico
13.
PLoS One ; 12(3): e0173343, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28301494

RESUMO

CONCLUSION: TUS findings of fluid bronchogram, multifocal involvement, and pleural effusion were associated with adverse outcomes, including longer hospital stay, ICU admission, and tube thoracotomy in hospitalized CAP children. Therefore, TUS is a novel tool for prognostic stratifications of CAP in hospitalized children.


Assuntos
Infecções Comunitárias Adquiridas/diagnóstico por imagem , Hospitalização , Pneumonia/diagnóstico por imagem , Ultrassonografia/métodos , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/terapia , Feminino , Humanos , Masculino , Pneumonia/terapia , Estudos Retrospectivos , Resultado do Tratamento
14.
PLoS One ; 11(10): e0165440, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27792747

RESUMO

BACKGROUND: Rhinitis and asthma share similar immunopathological features. Rhinomanometry is an important test used to assess nasal function and spirometry is an important tool used in asthmatic children. The degree to which the readouts of these tests are correlated has yet to be established. We sought to clarify the relationship between rhinomanometry measurements, fractional exhaled nitric oxide (FeNO), and spirometric measurements in asthmatic children. METHODS: Patients' inclusion criteria: age between 5 and 18 years, history of asthma with nasal symptoms, and no anatomical deformities. All participants underwent rhinomanometric evaluations and pulmonary function and FeNO tests. RESULTS: Total 84 children were enrolled. By rhinomanometry, the degree of nasal obstruction was characterized as follows: (1) no obstruction in 33 children, (2) slight obstruction in 29 children, and (3) moderate obstruction in 22 children. FeNO was significantly lower in patients without obstruction than those with slight or moderate obstruction. Dividing patients according to ATS Clinical Practice Guidelines regarding FeNO, patients < 12 years with FeNO > 20 ppb had a lower total nasal airflow rate than those with FeNO < 20 ppb. Patients ≥ 12 years with FeNO > 25 ppb had a lower total nasal airflow rate than those with FeNO < 25 ppb. CONCLUSIONS: Higher FeNO was associated with a lower nasal airflow and higher nasal resistance. This supports a relationship between upper and lower airway inflammation, as assessed by rhinomanometry and FeNO. The results suggest that rhinomanometry may be integrated as part of the functional assessment of asthma.


Assuntos
Asma/diagnóstico , Asma/fisiopatologia , Expiração , Óxido Nítrico/metabolismo , Nariz/fisiopatologia , Ventilação Pulmonar , Rinomanometria , Adolescente , Asma/sangue , Asma/complicações , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulina E/sangue , Masculino , Rinite Alérgica/complicações , Espirometria , Inquéritos e Questionários
15.
Health Phys ; 109(1): 69-77, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26011499

RESUMO

This study investigated radiation exposures from nuclear medicine patients by systematically comparing the dose rates calculated using various source models, ranging from simplified point, line, and cylinder sources to high-quality anthropomorphic phantoms. Three widely used radionuclides, (99m)Tc, (18)F, and I(131), were considered in these source models with uniform or organ-dependent distributions. Conducting Monte Carlo simulations with anthropomorphic phantoms is a realistic but time-consuming approach. The point source model is simple but too conservative, overestimating dose rates by approximately a factor of 2 at a distance of 30 cm and by 30-40% at 1 m. Both the line and cylinder source models provided improved estimates, reducing the overestimation of dose rates to 10-20% at distances of interest. The line source model was comparable to the cylinder source model because of the offset of two competing effects (i.e., attenuation and buildup) caused by the source volume. The influence of various photon energies and cylinder sizes on the result of compensating errors was examined to evaluate the effective range of the line source model. The line source model, which is relatively easy to implement and predicts slightly conservative dose rates, is considered the most practical method for calculating dose rates near radioactive patients. An application of the line source model to 51 post-thyroidectomy patients in Taiwan was demonstrated. The consistency between calculations and measurements was satisfactory after considering the room-scattering effect.


Assuntos
Radioisótopos do Iodo/uso terapêutico , Método de Monte Carlo , Imagens de Fantasmas , Doses de Radiação , Monitoramento de Radiação , Neoplasias da Glândula Tireoide/radioterapia , Antropometria , Humanos , Proteção Radiológica , Taiwan
16.
J Oral Pathol Med ; 42(7): 565-9, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23438080

RESUMO

BACKGROUND: Expression of Gα12 is found to be associated with cancer cell proliferation, migration, invasion, and metastasis. METHODS: This study used immunohistochemistry to examine the expression of Gα12 protein in 100 specimens of oral squamous cell carcinoma (OSCC), 45 specimens of oral epithelial dysplasia (OED), and 36 specimens of normal oral mucosa (NOM). RESULTS: The mean Gα12 labeling indices (LIs, defined as the percentage of positive cells in total cells) increased significantly from NOM (7 ± 11%) through OED (21 ± 20%) to OSCC samples (53 ± 33%, P < 0.001). The higher mean Gα12 LI was significantly associated with OSCCs with larger tumor size (P = 0.003), positive lymph node metastasis (P = 0.002), or more advanced clinical stages (P = 0.003). Positive lymph node metastasis (P = 0.039) and Gα12 LI > 50% (P = 0.009) were identified as independent unfavorable prognosis factors by multivariate analyses with Cox regression model. Moreover, Kaplan-Meier curve showed that OSCC patients with a Gα12 LI > 50% had a significantly poorer cumulative survival than those with a Gα12 LI ≤ 50% (log-rank test, P = 0.009). CONCLUSIONS: Our results showed a stepwise and significant elevation in Gα12 protein expression from NOM through OED to OSCCs, suggesting that overexpression of Gα12 protein may be an early event in oral carcinogenesis and may play a pivotal role in oral cancer development. Moreover, the Gα12 protein can be a biomarker for prediction of the progression of OSCCs and the prognosis of patients with OSCC in Taiwan.


Assuntos
Carcinoma de Células Escamosas/patologia , Subunidades alfa G12-G13 de Proteínas de Ligação ao GTP/análise , Neoplasias Bucais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinogênese , Carcinoma de Células Escamosas/secundário , Movimento Celular/fisiologia , Proliferação de Células , Citoplasma/patologia , Progressão da Doença , Epitélio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Invasividade Neoplásica , Estadiamento de Neoplasias , Lesões Pré-Cancerosas/patologia , Prognóstico , Taxa de Sobrevida , Adulto Jovem
17.
PLoS One ; 6(4): e18702, 2011 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-21494560

RESUMO

Phosphatidylinositol 3-kinase (PI3 kinase) mediates gastrulation cell migration in zebrafish via its regulation of PIP(2)/PIP(3) balance. Although PI3 kinase counter enzyme PTEN has also been reported to be essential for gastrulation, its role in zebrafish gastrulation has been controversial due to the lack of gastrulation defects in pten-null mutants. To clarify this issue, we knocked down a pten isoform, ptenb by using anti-sense morpholino oligos (MOs) in zebrafish embryos and found that ptenb MOs inhibit convergent extension by affecting cell motility and protrusion during gastrulation. The ptenb MO-induced convergence defect could be rescued by a PI3-kinase inhibitor, LY294002 and by overexpressing dominant negative Cdc42. Overexpression of human constitutively active akt1 showed similar convergent extension defects in zebrafish embryos. We also observed a clear enhancement of actin polymerization in ptenb morphants under cofocal microscopy and in actin polymerization assay. These results suggest that Ptenb by antagonizing PI3 kinase and its downstream Akt1 and Cdc42 to regulate actin polymerization that is critical for proper cell motility and migration control during gastrulation in zebrafish.


Assuntos
Gastrulação , Fosfoproteínas Fosfatases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo , Proteína cdc42 de Ligação ao GTP/metabolismo , Actinas/metabolismo , Animais , Movimento Celular/efeitos dos fármacos , Embrião não Mamífero/citologia , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/enzimologia , Desenvolvimento Embrionário/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Gastrulação/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Genes Dominantes/genética , Humanos , Modelos Biológicos , Oligonucleotídeos Antissenso/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Fosfoproteínas Fosfatases/deficiência , Polimerização/efeitos dos fármacos , Biossíntese de Proteínas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteínas de Peixe-Zebra/deficiência
18.
PLoS One ; 5(12): e15331, 2010 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-21203473

RESUMO

During gastrulation, cohesive migration drives associated cell layers to the completion of epiboly in zebrafish. The association of different layers relies on E-cadherin based cellular junctions, whose stability can be affected by actin turnover. Here, we examined the effect of malfunctioning actin turnover on the epibolic movement by knocking down an actin depolymerizing factor, cofilin 1, using antisense morpholino oligos (MO). Knockdown of cfl1 interfered with epibolic movement of deep cell layer (DEL) but not in the enveloping layer (EVL) and the defect could be specifically rescued by overexpression of cfl1. It appeared that the uncoordinated movements of DEL and EVL were regulated by the differential expression of cfl1 in the DEL, but not EVL as shown by in situ hybridization. The dissociation of DEL and EVL was further evident by the loss of adhesion between layers by using transmission electronic and confocal microscopy analyses. cfl1 morphants also exhibited abnormal convergent extension, cellular migration and actin filaments, but not involution of hypoblast. The cfl1 MO-induced cell migration defect was found to be cell-autonomous in cell transplantation assays. These results suggest that proper actin turnover mediated by Cfl1 is essential for adhesion between DEL and EVL and cell movements during gastrulation in zebrafish.


Assuntos
Cofilina 1/metabolismo , Gástrula/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Sequência de Aminoácidos , Animais , Caderinas/metabolismo , Adesão Celular , Movimento Celular , Hibridização In Situ , Microscopia Confocal/métodos , Microscopia Eletrônica de Transmissão/métodos , Modelos Biológicos , Dados de Sequência Molecular , Homologia de Sequência de Aminoácidos , Peixe-Zebra
20.
J Psychiatry Neurosci ; 33(1): 47-53, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18197272

RESUMO

OBJECTIVE: The Val158Met polymorphism of the catechol-O-methyltransferase gene has been demonstrated to be associated with prefrontal executive function explaining 4% of variance in perseverative errors on the Wisconsin Card Sorting Test (WCST). Studies suggest that dopamine D(1) and D(3) and serotonin 5-HT(2A) and 5-HT(6) receptors may also be involved in prefrontal cognitive function and that genetic polymorphisms (D(1) A-48G, D(3) Ser9Gly, 5-HT(2A) T102C, and 5-HT(6) T267C) of these receptors may be associated with brain glucose metabolism or neurophysiological function. The current study's objective was to investigate whether executive function varies with these genetic variations. METHODS: A sample of 216 healthy Han Chinese adults were measured with the WCST and genotyped for the 4 genetic polymorphisms. RESULTS: Kruskal-Wallis tests showed a significant difference in WCST perseverative errors among the genotypes D(3) Ser9Gly (p = 0.009), 5-HT(2A) T102C (p = 0.038) and 5-HT(6) T267C (p = 0.010), but not in the genotype D(1) A-48G. Multiple regression analysis for the WCST natural logarithm values (i.e., for fulfilling the normal distribution requirement) showed that subjects' perseverative errors were significantly influenced by D(1) A-48G, D(3) Ser9Gly, 5-HT(2A) T102C and 5-HT(6) T267C polymorphisms after adjustment of other variables. CONCLUSION: The preliminary data suggest that D(1), D(3), 5-HT(2A) and 5-HT(6) genetic mutations may influence prefrontal executive cognition in healthy adults. Further studies in larger samples with other ethnicities or in mentally ill patients are warranted.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Cognição/fisiologia , Variação Genética/genética , Nível de Saúde , Córtex Pré-Frontal/fisiologia , Receptor 5-HT2A de Serotonina/genética , Receptores de Dopamina D1/genética , Receptores de Dopamina D3/genética , Receptores de Serotonina/genética , Adulto , Idoso , Primers do DNA/genética , Feminino , Expressão Gênica/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/genética
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