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1.
Disabil Health J ; 17(3): 101612, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38503622

RESUMO

Disability awareness and competency trainings are an important component of addressing ableism and health equity in the health promotion context. This commentary describes our process of developing, implementing, and refining a disability competency training, the Inclusive Community Exercise Training, for community-based group exercise instructors. The training originated from a partnership between academic researchers, community organizations, and individuals with disabilities. After initial pilot testing, we used feedback from participants to enhance the training. To optimize successful dissemination of this training, we utilized the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, which is widely used in public health. The revision process focused on generalizing content to suit a wider audience, utilizing an eLearning platform for dissemination, and optimizing interactivity to improve learning effectiveness. The commentary emphasizes the lessons learned and the significance of systematic program revision, considering diverse expertise, content tailoring, and the benefits of accessible eLearning platforms.


Assuntos
Conscientização , Pessoas com Deficiência , Promoção da Saúde , Humanos , Pessoas com Deficiência/educação , Projetos Piloto , Promoção da Saúde/métodos , Avaliação de Programas e Projetos de Saúde/métodos , Exercício Físico , Conhecimentos, Atitudes e Prática em Saúde
2.
Neurochirurgie ; 68(5): 493-497, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35623915

RESUMO

BACKGROUND: Moyamoya disease (MMD) affects young patients, is generally progressive, and results in strokes or cerebral hemorrhages for which medical management is not effective. OBJECTIVE: To determine the effectiveness of surgical management with minimally invasive cerebral revascularization in MMD. MATERIAL AND METHODS: We conducted a retrospective cohort study of patients undergoing extracranial-intracranial microsurgical revascularization surgery with mini-craniotomy, analyzing the epidemiological, clinical, neuroimaging, postoperative evolution, and complications. We describe the technique in detail. Key outcomes included graft patency, complications, and recurrence of ischemic or hemorrhagic stroke. RESULTS: From September 2017 to December 2020, 12 brain revascularization procedures for MMD were performed in eight patients (four bilateral), and all 12 grafts were classified as patent. The main complication was contralateral cerebral infarction identified by postoperative neuroimaging in a patient without clinical symptomatology. There was no case of scalp ischemia or necrosis when performing the minimally invasive approach with linear incision. CONCLUSIONS: The results of this study suggest that the minimally invasive extracranial-intracranial cerebral revascularization procedure for MMD in adults is effective, with graft patency in all cases and minimal morbidity.


Assuntos
Revascularização Cerebral , Doença de Moyamoya , Adulto , Hemorragia Cerebral , Revascularização Cerebral/métodos , Humanos , Doença de Moyamoya/complicações , Doença de Moyamoya/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
3.
J Prev Alzheimers Dis ; 8(1): 92-99, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33336230

RESUMO

AIMS: This study examined the interactive effect of physical fitness and Apolipoprotein e4 on intelligence and cortical networking in adolescents. METHODS: Participants were middle school students consisting of 10 and 8 high- and low-fit e4 carriers (e4+), respectively, and 14 and 10 high- and low-fit non-carriers (e4-), respectively. Inter- and intra-hemispheric coherences were calculated to examine cortico-cortical communication during intelligence test. RESULTS: Coherence in low-fit e4+ was lower than in high-fit e4+, while coherence in low-fit e4- was similar to or higher than in high-fit e4-. CONCLUSION: the presence of the e4 allele can decrease neural networking 50-60 years before Alzheimer's disease onset: however, physical fitness may compensate for the negative impact of genotype. Moreover, the beneficial effects of physical fitness may differ depending on functional states of the adolescent brain according to the presence of the e4 allele.


Assuntos
Apolipoproteína E4/genética , Inteligência , Rede Nervosa/fisiologia , Aptidão Física/fisiologia , Adolescente , Cognição , Feminino , Genótipo , Heterozigoto , Humanos , Masculino
4.
Phys Rev E ; 101(5-1): 053207, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32575181

RESUMO

We studied parallel propagating electromagnetic waves in a magnetized quantum electron plasma of finite temperature, as an extension of our previous study on a zero temperature plasma. We obtained simple analytic dispersion relations in the long wavelength limit that included the thermal effect as correction terms to the zero temperature results. As in the zero temperature case, the lower branch of the R wave showed significant damping and became ill-defined at short wavelengths. Quantum effects seemed to give qualitative changes, such as the appearance of anomalous dispersion regions, to the classical dispersion relations when v_{F}/v_{th}≤0.2 for a set of exemplary parameters of v_{F}=0.1c and ω_{ce}/ω_{pe}=0.05 was used. We also noted that introduction of the Planck constant in the quantum Vlasov equation changed the shape of the anomalous dispersion region qualitatively, by forming a normal dispersion region in the middle of the original single broad anomalous dispersion region.

5.
Int J Pharm ; 560: 47-56, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30641184

RESUMO

The surface structure of crystalline particles affects the functionality of the particles in drug delivery. Prediction of the final structure of particles that crystallize easily within the spray drying process is of interests for many applications. A theoretical framework was developed for the prediction of crystal structure precipitating on the surface of the particle. This model was based on the dimensionless Damkohler number (Da), to be an indicator of final particle morphology. Timescales of evaporation and reaction were required for calculation of the Damkohler number. The modified evaporation time scale was estimated based on the time that is available for the crystal to precipitate after supersaturation. The reaction time scale was estimated based on the time scale for induction time. Mannitol was produced under different processing conditions in order to validate the theoretical model. Results showed for the high Damkohler numbers, the surface structure of the particle was rough, while smaller Damkohler numbers led to relatively smooth particle surfaces. Additionally, although the beta polymorph was dominant in all of the experiments, alpha polymorph was precipitated in the experiments with a large Damkohler number. The theoretical framework developed will be a useful predictive tool to guide the manipulation of particle crystallization in spray dryers.


Assuntos
Química Farmacêutica/métodos , Sistemas de Liberação de Medicamentos , Excipientes/química , Manitol/química , Cristalização , Dessecação , Modelos Teóricos , Propriedades de Superfície , Fatores de Tempo
6.
Hum Exp Toxicol ; 37(6): 636-646, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28741374

RESUMO

This study aimed to examine the effects of lipid emulsion on the vasodilation and cardiovascular depression induced by toxic doses of calcium channel blockers. The effects of lipid emulsion on the vasodilation induced by bepridil, verapamil, nifedipine, and diltiazem were investigated in isolated endothelium-denuded rat aortae. The effect of lipid emulsion on the comparable hemodynamic depression induced by the continuous infusion of a toxic dose of either verapamil or diltiazem was examined in an in vivo rat model. The results showed the following decreasing order for the magnitude of lipid emulsion-mediated inhibition of vasodilation: bepridil, verapamil, nifedipine, and diltiazem. Lipid emulsion (0.5-2%) reversed the vasodilation induced by a toxic dose of verapamil, whereas only a higher concentration (2%) reversed the vasodilation induced by a toxic dose of diltiazem. Pretreatment with lipid emulsion alleviated the systolic and mean blood pressure decreases induced by a toxic dose of verapamil, whereas it had no effect on the decrease induced by diltiazem. Taken together, these results suggest that lipid emulsion alleviates the severe vasodilation and systolic blood pressure decrease induced by a toxic dose of verapamil, and this alleviation appears to be associated with the relatively high lipid solubility of verapamil.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/toxicidade , Fosfolipídeos/uso terapêutico , Óleo de Soja/uso terapêutico , Vasodilatação/efeitos dos fármacos , Vasodilatadores/toxicidade , Verapamil/toxicidade , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiologia , Bepridil/toxicidade , Diltiazem/toxicidade , Emulsões/farmacologia , Emulsões/uso terapêutico , Técnicas In Vitro , Masculino , Nifedipino/toxicidade , Fenilefrina/farmacologia , Fosfolipídeos/farmacologia , Ratos , Ratos Sprague-Dawley , Óleo de Soja/farmacologia
7.
Spinal Cord ; 55(10): 906-910, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28485386

RESUMO

STUDY DESIGN: Single-center retrospective study. OBJECTIVES: To evaluate the monitoring rate, sensitivity and specificity of intraoperative monitoring (IOM) during removal of intradural extramedullary (IDEM) or epidural metastatic spinal tumors. Also, to assess the efficacy of monitoring somatosensory-evoked potentials (SSEP) when motor-evoked potentials (MEP) are not measurable. SETTING: The Neuro-Oncology Clinic, National Cancer Center, Korea. METHODS: Patients (n=101) with IDEM or epidural metastatic spinal tumors at the cord level underwent surgeries monitored with SSEP and/or MEP. The monitoring rate was defined as negative when MEP or SSEP could not be measured after reversal of the neuromuscular block under general anesthesia. Positive IOM changes included more than a 50% change in the MEP or SSEP amplitude and more than a 10% delay in SSEP latency. RESULTS: MEP was measurable in 73% of patients. The MEP monitoring rate in patients with motor power grades of 3 or less was 39%, which was lower than that of SSEP (83%). The sensitivity, specificity and predictability of MEP for motor changes were 93, 90 and 91%, respectively. Conversely, the sensitivity, specificity and predictability of SSEP were 62, 97 and 89%, respectively. In patients in whom MEP was not measurable (n=24), SSEP was monitored with a predictability of 83%. CONCLUSION: In cases of extramedullary spinal tumors, MEP shows a higher sensitivity than SSEP does. However, the monitoring rate of MEP in non-ambulatory patients was lower than that of SSEP. In those cases, SSEP can be useful to monitor for postoperative neurological deficits.


Assuntos
Neoplasias Epidurais/fisiopatologia , Neoplasias Epidurais/cirurgia , Monitorização Neurofisiológica Intraoperatória , Neoplasias da Medula Espinal/fisiopatologia , Neoplasias da Medula Espinal/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Epidurais/secundário , Potencial Evocado Motor , Potenciais Somatossensoriais Evocados , Estudos de Viabilidade , Feminino , Humanos , Monitorização Neurofisiológica Intraoperatória/métodos , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/diagnóstico , Transtornos dos Movimentos/etiologia , Transtornos dos Movimentos/prevenção & controle , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias da Medula Espinal/secundário , Resultado do Tratamento , Adulto Jovem
8.
J Dairy Sci ; 97(9): 5303-14, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24997659

RESUMO

Mixing surfactants with whole milk feed before spray drying could be a commercially favorable approach to produce instant whole milk powders in a single step. Pure whole milk powders obtained directly from spray drying often have a high surface fat coverage (up to 98%), rendering them less stable during storage and less wettable upon reconstitution. Dairy industries often coat these powders with lecithin, a food-grade surfactant, in a secondary fluidized-bed drying stage to produce instant powders. This study investigated the changes in wetting behavior on the surface of a whole milk particle caused by the addition of surfactants before drying. Fresh whole milk was mixed with 0.1% (wt/wt) Tween 80 or 1% (wt/wt) lecithin (total solids), and the wetting behavior of the shell formed by each sample was captured using a single-droplet drying device at intermediate drying stages as the shell was forming. The addition of surfactants improved shell wettability from the beginning of shell formation, producing more wettable milk particles after drying. The increase in surfactant loading by 10 times reduced the wetting time from around 30s to <5s. At the same loading of 1% (wt/wt; total solids), milk particles with Tween 80 were much more wettable than those with lecithin (<5s compared with >30s). We proposed that Tween 80 could adsorb at the oil-water interface of fat globules, making the surface fat more wettable, whereas lecithin tends to combine with milk proteins to form a complex, which then competes for the air-water surface with fat globules. Spray-drying experiments confirmed the greatly improved wettability of whole milk powders by the addition of either 0.1% (wt/wt) Tween 80 or 1% (wt/wt) lecithin; wetting time was reduced from 35±4s to <15s. To the best of our knowledge, this is the first time that a dynamic droplet drying system has been used to elucidate the complex interactions between ionic or nonionic surfactants and milk components (both proteins and fat), as well as the resultant effect on the development of milk particle functionality during drying.


Assuntos
Manipulação de Alimentos/métodos , Leite/química , Tensoativos/química , Molhabilidade , Animais , Dessecação , Lecitinas/química , Proteínas do Leite/química , Pós/química , Água/análise
9.
Artigo em Inglês | MEDLINE | ID: mdl-24927278

RESUMO

New tandem mass spectrometric method coupled with liquid chromatography (LC-MS/MS) has been developed to determine the total concentration of camptothecin derivatives (irinotecan and SN-38) regardless of inter-conversion phenomenon between carboxylate and lactone forms. At first, all sample solutions were acidified for 1h in order to completely convert CPT derivatives into their lactone forms and then CPT derivatives were extracted with organic solution containing diethyl ether and ethyl acetate (2:1, v/v) just after alkalization in the range pH 8.0-8.5 in acid-treated solutions. Analytes were separated on a reverse phase C18 column (150×2.1mm) and eluted isocratically with a mobile phase which consisted of acetonitrile-methanol-buffer (0.1% formic acid, 5mM ammonium formate) (3:4:3, v/v). CPT derivatives were monitored by tandem mass spectrometry in electrospay-positive ionization and multiple reaction mode programmed to the following transitions (m/z): '587.6→167.2' of CPT-11, '393.6→349.3' of SN-38 and '349.4→ 305.2' of CPT. The method was validated to have the proper linearity (r(2)>0.99) over the range of 5-1000ng/ml of CPT-11 and 1-250ng/ml of SN-38 with good accuracy (89.8-114.3%) and precision (less than 10%). In all stability tests, concentration of CPT-11 and SN-38 had been left in the acceptable range of 88.8-110.7% when sample solutions were acidified before determination of CPT derivatives. Newly developed LC-MS/MS method was suitable for the determination of CPT derivatives of both rabbit plasma and tumor tissues in the pharmacokinetic study.


Assuntos
Antineoplásicos Fitogênicos/farmacocinética , Camptotecina/análogos & derivados , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Animais , Antineoplásicos Fitogênicos/sangue , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/metabolismo , Camptotheca/química , Camptotecina/sangue , Camptotecina/isolamento & purificação , Camptotecina/metabolismo , Camptotecina/farmacocinética , Irinotecano , Limite de Detecção , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Coelhos , Reprodutibilidade dos Testes
10.
Skin Res Technol ; 20(4): 422-8, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24506419

RESUMO

BACKGROUND: Long-term exposure to sunlight changes skin features like amount of facial wrinkling and skin elasticity, which is useful in estimating skin health and age-related changes. Skin elasticity is evaluated by quantitative methods such as the noninvasive suction device Cutometer(®) , which is widely used to evaluate regional body-elasticity differences and correlate these findings with the results of other instrumental data. Few field studies have been done with the Ballistometer(®) device, another noninvasive method for measuring skin elasticity. METHOD: In this study, we measured the skin elasticity of each subject's forehead, cheek, and volar forearm using two devices with different means of obtaining quantitative measurements - Ballistometer(®) (Diastron Ltd.) and Cutometer(®) (CK electronics). RESULTS: The results from testing with the Ballistometer(®) and Cutometer(®) devices showed that the degree of skin elasticity of the volar forearm is greater than those found on the cheek and forehead. The parameters measured by the Ballistometer(®) showed high correlation patterns. On the cheek skin, the correlation coefficient between Ballisto-parameters and R parameters (R0, R3, R8) was higher than other skin sites. CONCLUSION: Taken together, R parameters measured by the Cutometer(®) device have been widely distributed in the evaluation of skin elasticity in research and cosmetics. Although the methodologies are different, the Ballistometer(®) device is also a useful tool to evaluate skin elasticity.


Assuntos
Módulo de Elasticidade/fisiologia , Testes de Dureza/instrumentação , Manometria/instrumentação , Estimulação Física/instrumentação , Fenômenos Fisiológicos da Pele , Adulto , Desenho de Equipamento , Análise de Falha de Equipamento , Feminino , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estresse Mecânico
11.
Trop Biomed ; 31(4): 600-6, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25776585

RESUMO

Mismatch specific endonuclease (MSE) method was used to detect natural polymorphisms in Pvs25 and Pv38 genes of Plasmodium vivax. Eighty seven patients with P. vivax were recruited in the Republic of Korea (ROK). Pvs25 and Pv38 genes were amplified by polymerase chain reaction (PCR), and the PCR amplicons were mixed with reference DNA sequences. Following the denaturation and gradual annealing, the product mixtures were cleaved by the MSE. Heteroduplex types were readily detected by gel electrophoresis, where extra bands with shorter sizes would appear from the cleavage. After MSE cleavage of 657- bp product from Pvs25 mixtures, three genotypes were detected, while Pv38 mixtures with 1220-bp products presented two genotypes in ROK isolates. After the MSE cleavage, the mismatched samples of Pvs25 and Pv38 were completely sequenced, and the results were in complete agreement with the MSE analyses. In conclusion, genotyping of Pvs25 and Pv38 with MSE cleavage could be a potential method for the high-throughput screening of the large field samples.


Assuntos
Endonucleases , Técnicas de Genotipagem/métodos , Plasmodium vivax/classificação , Plasmodium vivax/genética , Proteínas de Protozoários/genética , Genótipo , Humanos , Malária Vivax/parasitologia , Plasmodium vivax/isolamento & purificação , Polimorfismo Genético , República da Coreia , Fatores de Tempo
12.
Leukemia ; 27(8): 1628-36, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23385375

RESUMO

Panobinostat is a potent oral pandeacetylase inhibitor that leads to acetylation of intracellular proteins, inhibits cellular proliferation and induces apoptosis in leukemic cell lines. A phase Ia/II study was designed to determine the maximum-tolerated dose (MTD) of daily panobinostat, administered on two schedules: three times a week every week or every other week on a 28-day treatment cycle in patients with advanced hematologic malignancies. The criteria for hematologic dose-limiting toxicities differed between patients with indications associated with severe cytopenias at baseline (leukemia and myeloid disorders) and those less commonly associated with baseline cytopenias (lymphoma and myeloma). In patients with leukemia and myeloid disorders, 60 mg was the MTD for weekly as well as biweekly panobinostat. In patients with lymphoma and myeloma, 40 mg was the recommended dose for phase II evaluation (formal MTD not determined) of weekly panobinostat, and 60 mg was the MTD for biweekly panobinostat. Overall, panobinostat-related grade 3-4 adverse events included thrombocytopenia (41.5%), fatigue (21%) and neutropenia (21%). Single-agent activity was observed in several indications, including Hodgkin lymphoma and myelofibrosis. This phase Ia/II study provided a broad analysis of the safety profile and efficacy of single-agent panobinostat in patients with hematologic malignancies.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Hematológicas/tratamento farmacológico , Inibidores de Histona Desacetilases/uso terapêutico , Ácidos Hidroxâmicos/uso terapêutico , Indóis/uso terapêutico , Acetilação , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Esquema de Medicação , Feminino , Neoplasias Hematológicas/diagnóstico , Inibidores de Histona Desacetilases/administração & dosagem , Inibidores de Histona Desacetilases/efeitos adversos , Histonas/metabolismo , Humanos , Ácidos Hidroxâmicos/administração & dosagem , Ácidos Hidroxâmicos/efeitos adversos , Indóis/administração & dosagem , Indóis/efeitos adversos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Panobinostat , Resultado do Tratamento , Adulto Jovem
13.
Langmuir ; 28(39): 13772-6, 2012 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-22950653

RESUMO

A simultaneous convection-dehydration and antisolvent precipitation approach has been shown to produce uniform microsized lactose particles from aqueous droplet at atmospheric pressure. Microparticles with high uniformity having diameters of between 1.0 and 2.4 µm have been obtained. The precipitation of the microparticles is driven by a unique self-assembly mechanism that cannot be fully elucidated by supersaturation alone. Further analysis suggests that structural changes in the solvent/antisolvent mixture, due to hydrophobic hydration, could play a role in the precipitation process observed.


Assuntos
Atmosfera/química , Lactose/química , Microesferas , Desidratação , Interações Hidrofóbicas e Hidrofílicas , Tamanho da Partícula , Pressão , Propriedades de Superfície , Água/química
14.
Br J Dermatol ; 167(4): 914-21, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22632542

RESUMO

BACKGROUND: Colchicine, a first-line drug for the treatment of Behçet disease (BD), inhibits caspase-1 activation and inflammatory cytokine production. However, therapeutic and preventive effects are not observed in some patients with BD. OBJECTIVE: To explore whether the effects of colchicine on proinflammatory cytokine expression and cell death in peripheral blood mononuclear cells (PBMCs) from patients with BD are associated with responsiveness to colchicine. METHODS: Activation of caspase-1, transcription and secretion of interleukin (IL)-1ß, tumour necrosis factor (TNF)-α and IL-6, and release of lactate dehydrogenase (LDH) in PBMCs isolated from healthy controls and patients with BD were analysed in the presence or absence of colchicine and upon stimulation with lipopolysaccharide (LPS) plus a caspase-1 activator. RESULTS: Colchicine significantly modulated monosodium urate-induced IL-1ß release, LPS-stimulated LDH release, and basal transcript levels of TNF-α and IL-6 in healthy controls and BD colchicine responders, but not in BD colchicine nonresponders. Notably, colchicine showed contrasting effects on LPS-stimulated IL-1ß transcription, i.e. it increased in responders but decreased in nonresponders. Also, higher levels of TNF-α and IL-6 transcripts were observed in LPS-stimulated PBMCs from nonresponders compared with responders. CONCLUSIONS: This study shows different effects of colchicine on PBMCs from patients with BD according to their responsiveness to colchicine. Predicting responsiveness to colchicine in patients with BD may, therefore, be possible by examining alterations in IL-1ß transcript levels in LPS-stimulated PBMCs after colchicine treatment.


Assuntos
Síndrome de Behçet/tratamento farmacológico , Colchicina/farmacologia , Citocinas/metabolismo , Supressores da Gota/farmacologia , Adulto , Síndrome de Behçet/metabolismo , Células Sanguíneas/efeitos dos fármacos , Células Sanguíneas/metabolismo , Colchicina/farmacocinética , Citocinas/efeitos dos fármacos , Feminino , Supressores da Gota/farmacocinética , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Resultado do Tratamento
15.
Diabetologia ; 2012 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-22301943

RESUMO

AIMS/HYPOTHESIS: Islet amyloid, which is mainly composed of human islet amyloid polypeptide (hIAPP), is a pathological characteristic of type 2 diabetes and also forms in cultured and transplanted islets. We used islet beta cells as well as two ex vivo models of islet amyloid formation, cultured human islets and hIAPP-expressing transgenic mouse islets with or without beta cell Fas deletion, to test whether: (1) the aggregation of endogenous hIAPP induces Fas upregulation in beta cells; and (2) deletion or blocking of Fas protects beta cells from amyloid toxicity. METHODS: INS-1, mouse or human islet cells were cultured with hIAPP alone, or with amyloid inhibitor or Fas antagonist. Non-transduced islets, and human islets or hIAPP-expressing mouse islets transduced with an adenovirus that delivers a human proIAPP-specific small interfering RNA (siRNA) (Ad-ProhIAPP-siRNA) were cultured to form amyloid. Mouse islets expressing hIAPP with or without Fas were similarly cultured. Beta cell Fas upregulation, caspase-3 activation, apoptosis and function, and islet IL-1ß levels were assessed. RESULTS: hIAPP treatment induced Fas upregulation, caspase-3 activation and apoptosis in INS-1 and islet cells. The amyloid inhibitor or Fas antagonist reduced apoptosis in hIAPP-treated beta cells. Islet cells with Fas deletion had lower hIAPP-induced beta cell apoptosis than those expressing Fas. Ad-ProhIAPP-siRNA-mediated amyloid inhibition reduced Fas upregulation and IL-1ß immunoreactivity in human and hIAPP-expressing mouse islets. Cultured hIAPP-expressing mouse islets with Fas deletion had similar amyloid levels, but lower caspase-3 activation and beta cell apoptosis, and a higher islet beta:alpha cell ratio and insulin response to glucose, compared with islets expressing Fas and hIAPP. CONCLUSIONS/INTERPRETATION: The aggregation of biosynthetic hIAPP produced in islets induces beta cell apoptosis, at least partially, via Fas upregulation and the Fas-mediated apoptotic pathway. Deletion of Fas protects islet beta cells from the cytotoxic effects of endogenously secreted (and exogenously applied) hIAPP.

16.
Neuroscience ; 178: 261-9, 2011 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-21256194

RESUMO

Congenital central hypoventilation syndrome (CCHS), a condition associated with mutations in the PHOX2B gene, is characterized by loss of breathing drive during sleep, insensitivity to CO2 and O2, and multiple somatomotor, autonomic, neuropsychological, and ophthalmologic deficits, including impaired intrinsic and extrinsic eye muscle control. Brain structural studies show injury in peri-callosal regions and the corpus callosum (CC), which has the potential to affect functions disturbed in the syndrome; however, the extent of CC injury in CCHS is unclear. Diffusion tensor imaging (DTI)-based fiber tractography procedures display fiber directional information and allow quantification of fiber integrity. We performed DTI in 13 CCHS children (age, 18.2±4.7 years; eight male) and 31 control (17.4±4.9 years; 18 male) subjects using a 3.0-Tesla magnetic resonance imaging scanner; CC fibers were assessed globally and regionally with tractography procedures, and fiber counts and densities compared between groups using analysis-of-covariance (covariates; age and sex). Global CC evaluation showed reduced fiber counts and densities in CCHS over control subjects (CCHS vs. controls; fiber-counts, 4490±854 vs. 5232±777, P<0.001; fiber-density, 10.0±1.5 vs. 10.8±0.9 fibers/mm2, P<0.020), and regional examination revealed that these changes are localized to callosal axons projecting to prefrontal (217±47 vs. 248±32, P<0.005), premotor (201±51 vs. 241±47, P<0.012), parietal (179±64 vs. 238±54, P<0.002), and occipital regions (363±46 vs. 431±82, P<0.004). Corpus callosum fibers in CCHS are compromised in motor, cognitive, speech, and ophthalmologic regulatory areas. The mechanisms of fiber injury are unclear, but may result from hypoxia or perfusion deficits accompanying the syndrome, or from consequences of PHOX2B action.


Assuntos
Corpo Caloso/patologia , Fibras Nervosas Mielinizadas/patologia , Adolescente , Atrofia/patologia , Mapeamento Encefálico/métodos , Estudos de Casos e Controles , Criança , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Hipoventilação/congênito , Hipoventilação/patologia , Imageamento por Ressonância Magnética/métodos , Masculino , Vias Neurais/patologia , Reprodutibilidade dos Testes , Apneia do Sono Tipo Central/patologia , Adulto Jovem
17.
Diabetologia ; 53(7): 1415-27, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20369225

RESUMO

AIMS/HYPOTHESIS: Type 2 diabetes is characterised by decreased beta cell mass and islet amyloid formation. Islet amyloid formed by aggregation of human islet amyloid polypeptide (hIAPP) is associated with beta cell apoptosis. We used human and transgenic mouse islets in culture to examine whether deletion of caspase-3 protects islets from apoptosis induced by endogenously produced and exogenously applied hIAPP and compared hIAPP toxicity in islet alpha and beta cells. METHODS: Human and wild-type or caspase-3 knockout mouse islet cells were treated with hIAPP. Rat insulinoma INS-1 cells were similarly cultured with hIAPP and the amyloid inhibitor Congo Red or caspase-3 inhibitor. Human and hIAPP-expressing caspase-3 knockout mouse islets were cultured to form amyloid fibrils and assessed for beta and alpha cell apoptosis, beta cell function and caspase-3 activation. RESULTS: hIAPP-treated INS-1 cells had increased caspase-3 activation and apoptosis, both of which were reduced by inhibitors of amyloid or caspase-3. Similarly, hIAPP-treated human and mouse islet beta cells had elevated active caspase-3- and TUNEL-positive cells, whereas mouse islet cells lacking caspase-3 had markedly lower beta cell but comparable alpha cell apoptosis. During culture, human islets that formed amyloid had higher active caspase-3- and TUNEL-positive beta cells than those without detectable amyloid. Finally, cultured hIAPP-expressing mouse islets lacking caspase-3 had markedly lower beta cell apoptosis than those expressing caspase-3, associated with an increase in islet beta cell/alpha cell ratio, insulin content and glucose response. CONCLUSIONS/INTERPRETATION: Prevention of caspase-3 activation protects islet beta cells from apoptosis induced by fibrillogenesis of endogenously secreted and exogenously applied hIAPP. Islet beta cells are more susceptible to hIAPP toxicity than alpha cells cultured under the same conditions.


Assuntos
Amiloide/farmacologia , Caspase 3/fisiologia , Células Secretoras de Glucagon/citologia , Células Secretoras de Glucagon/efeitos dos fármacos , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Caspase 3/genética , Linhagem Celular , Células Cultivadas , Diabetes Mellitus Tipo 2/metabolismo , Células Secretoras de Glucagon/metabolismo , Humanos , Marcação In Situ das Extremidades Cortadas , Células Secretoras de Insulina/metabolismo , Polipeptídeo Amiloide das Ilhotas Pancreáticas , Camundongos , Camundongos Knockout , Ratos
18.
Neuroscience ; 167(4): 1249-56, 2010 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-20211704

RESUMO

Congenital central hypoventilation syndrome (CCHS) patients show significant autonomic dysfunction in addition to the well-described loss of breathing drive during sleep. Some characteristics, for example, syncope, may stem from delayed sympathetic outflow to the vasculature; other symptoms, including profuse sweating, may derive from overall enhanced sympathetic output. The dysregulation suggests significant alterations to autonomic regulatory brain areas. Murine models of the genetic mutations present in the human CCHS condition indicate brainstem autonomic nuclei are targeted; however, the broad range of symptoms suggests more widespread alterations. We used functional magnetic resonance imaging (fMRI) to assess neural response patterns to the Valsalva maneuver, an autonomic challenge eliciting a sequence of sympathetic and parasympathetic actions, in nine CCHS and 25 control subjects. CCHS patients showed diminished and time-lagged heart rate responses to the Valsalva maneuver, and muted fMRI signal responses across multiple brain areas. During the positive pressure phase of the Valsalva maneuver, CCHS responses were muted, but were less so in recovery phases. In rostral structures, including the amygdala and hippocampus, the normal declining patterns were replaced by increasing trends or more modest declines. Earlier onset responses appeared in the hypothalamus, midbrain, raphé pallidus, and left rostral ventrolateral medulla. Phase-lagged responses appeared in cerebellar pyramis and anterior cingulate cortex. The time-distorted and muted central responses to autonomic challenges likely underlie the exaggerated sympathetic action and autonomic dyscontrol in CCHS, impairing cerebral autoregulation, possibly exacerbating neural injury, and enhancing the potential for cardiac arrhythmia.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Apneia do Sono Tipo Central/fisiopatologia , Encéfalo/fisiopatologia , Feminino , Frequência Cardíaca , Humanos , Imageamento por Ressonância Magnética , Masculino , Apneia do Sono Tipo Central/congênito , Fatores de Tempo , Adulto Jovem
19.
J Appl Microbiol ; 108(1): 315-24, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20002911

RESUMO

AIMS: To assess the impact of reaerosolization from liquid impingement methods on airborne virus sampling. METHODS AND RESULTS: An AGI-30 impinger containing particles [MS2 bacteriophage or 30-nm polystyrene latex (PSL)] of known concentration was operated with sterile air. Reaerosolized particles as a function of sampling flow rate and particle concentration in the impinger collection liquid were characterized using a scanning mobility particle sizer. Reaerosolization from the impinger was also compared to that from a BioSampler. Results show that reaerosolization increases as flow rate increases. While the increased particle concentration in the impinger collection liquid leads to an increase in the reaerosolization of PSL particles, it does not necessarily lead to an increase in the reaerosolization of virus particles. Reaerosolization of virus particles begins to decrease as the particle concentration in the impinger collection liquid rises above 10(6) PFU ml(-1). This phenomenon results from aggregation of viral particles at high concentrations. Compared with micron-sized particles, nanosized virus particles are easier to aerosolize because of reduced inertia. Reaerosolization from the BioSampler is demonstrated to be significantly less than that from the impinger. CONCLUSIONS: Reaerosolization from impingement sampling methods is a mode of loss in airborne virus sampling, although it is not as significant a limitation as the primary particle size of the aerosol. Utilizing a BioSampler coupled with short sampling periods to prevent high accumulative concentrations can minimize the impact of reaerosolization. SIGNIFICANCE AND IMPACT OF THE STUDY: This study confirms reaerosolization of virus particles to be a mode of loss in impingement sampling and identifies methods to minimize the loss.


Assuntos
Levivirus , Material Particulado , Manejo de Espécimes/instrumentação , Manejo de Espécimes/métodos , Aerossóis
20.
Diabetologia ; 52(10): 2130-41, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19644667

RESUMO

AIMS/HYPOTHESIS: Pancreatic beta cells undergo dynamic remodelling during the perinatal period, with enhanced neogenesis, proliferation and apoptosis observed. The molecular mechanisms responsible for these processes have yet to be elucidated. Survivin is an inhibitor of apoptosis, first described as being exclusively expressed in tumour and embryonic tissues with regulatory functions in mitosis and apoptosis. The aim of the present study was to define the essential physiological role of survivin in the pancreas. METHODS: The expression profile of survivin was assessed in the mouse pancreas, and we generated a Pdx1 promoter-driven Survivin (also known as Birc5) knockout mouse using the Cre-loxP recombination system to determine the essential physiological function of survivin in the pancreas. RESULTS: Survivin is transiently expressed in mouse pancreatic islets during the embryonic and neonatal periods. Targeted deletion of Survivin in the pancreas resulted in a significant decline in beta cell mass throughout the perinatal period, leading to glucose intolerance in the adult. Survivin-deficient islets showed decreased cell proliferation as a result of a delay in cell cycle progression with perturbations in cell cycle proteins. Survivin did not, however, play an essential role in beta cell apoptosis either during the physiological remodelling period or in response to streptozotocin. Islet development, islet architecture, microvasculature and apoptosis were not affected by the absence of survivin in the pancreas. CONCLUSIONS/INTERPRETATION: Survivin expression in the pancreatic islets during the perinatal remodelling period is essential for the establishment of beta cell mass through cell cycle regulation.


Assuntos
Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/metabolismo , Proteínas Associadas aos Microtúbulos/fisiologia , Animais , Western Blotting , Proliferação de Células , Feminino , Citometria de Fluxo , Imuno-Histoquímica , Proteínas Inibidoras de Apoptose , Células Secretoras de Insulina/fisiologia , Masculino , Camundongos , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Pâncreas/metabolismo , Proteínas Repressoras , Survivina
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