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1.
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
2.
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
3.
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
4.
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
5.
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.

6.
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
7.
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
8.
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
9.
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
10.
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
11.
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
12.
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.

13.
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
14.
Neuroscience ; 158(4): 1364-77, 2009 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-19056468

RESUMO

In addition to protective effects within the adult central nervous system (CNS), in vivo application of N-methyl-d-aspartate inhibitors such as (+) MK-801 have been shown to induce neurodegeneration in neonatal rats over a specific developmental period. We have systematically mapped the nature and extent of MK-801-induced neurodegeneration throughout the neonatal murine brain in order to genetically dissect the mechanism of these effects. Highest levels of MK-801-induced neurodegeneration are seen in the cerebellar external germinal layer; while mature neurons of the internal granule layer are unaffected by MK-801 treatment. Examination of external germinal layer neurons by electron microscopy, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) and bromodeoxyuridine (BrdU) labeling, and caspase-3 activation demonstrate that these neurons die through the process of programmed cell death soon after they exit from the cell cycle. Significantly, ablation of caspase-3 activity completely inhibited the MK-801-induced (and developmental) programmed cell death of external germinal layer neurons. Similar to caspase-3, inactivation of muscarinic acetylcholine receptors in vivo using scopolamine inhibited MK-801-induced programmed cell death. By contrast, the GABAergic agonist diazepam, either alone or in combination with MK-801, enhanced programmed cell death within external germinal layer neurons. These data demonstrate that, in vivo, cerebellar granule neurons undergo a dramatic change in intracellular signaling in response to molecules present in the local cellular milieu during their first 24 h following exit from the cell cycle.


Assuntos
Cerebelo/citologia , Cerebelo/crescimento & desenvolvimento , Neurônios/fisiologia , Células-Tronco/fisiologia , Análise de Variância , Animais , Animais Recém-Nascidos , Bromodesoxiuridina/metabolismo , Caspase 3/deficiência , Caspase 3/metabolismo , Morte Celular/efeitos dos fármacos , Morte Celular/genética , Cerebelo/efeitos dos fármacos , Antagonistas Colinérgicos/farmacologia , Diazepam/farmacologia , Maleato de Dizocilpina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Moduladores GABAérgicos/farmacologia , Marcação In Situ das Extremidades Cortadas/métodos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia Eletrônica de Transmissão/métodos , Degeneração Neural/induzido quimicamente , Degeneração Neural/genética , Degeneração Neural/patologia , Neurônios/efeitos dos fármacos , Neurônios/ultraestrutura , Escopolamina/farmacologia , Células-Tronco/efeitos dos fármacos
15.
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
17.
Int J Gynecol Cancer ; 18(6): 1234-47, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18217967

RESUMO

Serous borderline ovarian tumors (SBOTs) are differentiated, slow growing, noninvasive, and have a better prognosis than their invasive counterparts, but recurrence and progression to invasive carcinomas are common, and unlike high-grade serous carcinomas, they tend to be nonresponsive to chemotherapy. However, due to a lack of culture systems and animal models, information about the properties of SBOT and their changes with neoplastic progression is extremely limited. Our objective was to establish a cell culture model for SBOTs and to characterize their phenotype and genotype. We compared cultures derived from two SBOTs, one of which was a short-term culture containing a BRAF mutation but few other cytogenetic changes while the other culture developed into a spontaneously immortalized permanent cell line and had numerical and structural chromosomal abnormalities but lacked RAS/BRAF mutations. Both cultures formed whorl-like epithelial colonies and resembled low-grade invasive carcinomas by their secretion of CA125 and oviduct-specific glycoprotein, production of matrix metalloproteinases, E-cadherin expression, and telomerase activity. Other characteristics associated with neoplastic transformation, including invasiveness, anchorage-independent growth, and tumorigenicity, were not observed. Importantly, cell motility was reduced in both lines, likely contributing to the lack of invasiveness. The results reveal a striking phenotypic similarity between the two cell lines, regardless of their cytogenetic diversity, which suggests that their characteristic phenotype is regulated to a large degree by epigenetic and environmental factors. In conclusion, we have established the first permanent SBOT cell line, which provides a new model to elucidate the undefined relationship of SBOTs to invasive ovarian carcinomas.


Assuntos
Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Adulto , Animais , Sequência de Bases , Biomarcadores , Diferenciação Celular , Movimento Celular , Feminino , Dosagem de Genes/genética , Genótipo , Saúde , Humanos , Camundongos , Mutação/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , Fatores de Tempo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
18.
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
19.
Mol Cell Biol ; 17(7): 3566-79, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9199292

RESUMO

The pRB-related proteins p107 and p130 are thought to suppress growth in part through their associations with two important cell cycle kinases, cyclin A-cdk2 and cyclin E-cdk2, and transcription factor E2F. Although each protein plays a critical role in cell proliferation, the functional consequences of the association among growth suppressor, cyclin-dependent kinase, and transcription factor have remained elusive. In an attempt to understand the biochemical properties of such complexes, we reconstituted each of the p130-cyclin-cdk2 and p107-cyclin-cdk2 complexes found in vivo with purified, recombinant proteins. Strikingly, stoichiometric association of p107 or p130 with either cyclin E-cdk2 or cyclin A-cdk2 negated the activities of these kinases. The results of our experiments suggest that inhibition does not result from substrate competition or loss of cdk2 activation. Kinase inhibitory activity was dependent upon an amino-terminal region of p107 that is highly conserved with p130. Further, a role for this amino-terminal region in growth suppression was uncovered by using p107 mutants unable to bind E2F. To determine whether cellular complexes might display similar regulatory properties, we purified p130-cyclin A-cdk2 complexes from human cells and found that such complexes exist in two forms, one that contains E2F-4-DP-1 and one that lacks the heterodimer. These endogenous complexes behaved like the in vitro-reconstituted complexes, exhibiting low levels of associated kinase activity that could be significantly augmented by dissociation of p130. The results of these experiments suggest a mechanism whereby p130 and p107 suppress growth by inhibiting important cell cycle kinases.


Assuntos
Quinases relacionadas a CDC2 e CDC28 , Proteínas de Transporte , Proteínas de Ciclo Celular , Quinases Ciclina-Dependentes/fisiologia , Ciclinas/fisiologia , Inibidores do Crescimento , Proteínas Nucleares/fisiologia , Proteínas Serina-Treonina Quinases/fisiologia , Proteínas , Animais , Quinase 2 Dependente de Ciclina , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição E2F , Fator de Transcrição E2F4 , Humanos , Substâncias Macromoleculares , Mariposas , Fosfoproteínas , Proteínas Recombinantes , Proteína 1 de Ligação ao Retinoblastoma , Proteína p107 Retinoblastoma-Like , Proteína p130 Retinoblastoma-Like , Transdução de Sinais , Relação Estrutura-Atividade , Fator de Transcrição DP1 , Fatores de Transcrição/fisiologia
20.
Food Chem Toxicol ; 44(11): 1875-83, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16904806

RESUMO

The objective of this study was to investigate the hypolipidemic effects of powdered whole persimmon leaf supplement in rats fed high-fat diet. Three groups of male Sprague-Dawley rats during 6 weeks were fed different diet: normal control (NC), high-fat (HF), and high-fat supplemented with powdered whole persimmon leaf (PL; 5%, wt/wt) groups. Body weight and relative weight of interscapular brown adipose tissue were significantly lower in the PL group than in the HF group, while plasma leptin concentration was higher. The supplementation of persimmon leaf significantly lowered the plasma total cholesterol and triglyceride concentrations, whereas elevated the ratio of HDL-C/total-C and improved the atherogenic index. Persimmon leaf supplementation led the hepatic cholesterol and triglyceride values to similar levels to the NC group. Accumulation of hepatic lipid droplets and the epididymal white adipocyte size of PL group were diminished comparing to the HF group. Hepatic HMG-CoA and ACAT activities were significantly higher in the PL group than in other groups. Contents of fecal triglyceride, cholesterol and acidic sterol were significantly higher in the PL group than in the HF group. Accordingly, we suggest that supplementation of the powdered whole persimmon leaf improves plasma and hepatic lipid levels profile partly via the increased fecal lipids in high-fat fed rats. These beneficial effects may be due to the properties of its phenolic compounds (1.15 g/100g) and high fiber (63.48 g/100g) content in the powdered persimmon leaf.


Assuntos
Gorduras na Dieta/administração & dosagem , Diospyros/química , Hipolipemiantes/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Aumento de Peso/efeitos dos fármacos , Acil Coenzima A/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Animais , Colesterol/sangue , Colesterol/metabolismo , Modelos Animais de Doenças , Epididimo/efeitos dos fármacos , Epididimo/patologia , Lipoproteínas/sangue , Lipoproteínas/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Folhas de Planta/química , Ratos , Ratos Sprague-Dawley , Esterol O-Aciltransferase/metabolismo , Triglicerídeos/metabolismo
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