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1.
Lab Invest ; 96(7): 773-83, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27111286

RESUMO

Fibrosis is an ominous pathological process in failing myocardium, but its pathogenesis is poorly understood. We recently reported that loss of an extracellular matrix (ECM) protein, fibulin-2, protected against ventricular dysfunction after myocardial infarction (MI) in association with absence of activation of transforming growth factor (TGF)-ß signaling and suppressed upregulation of ECM protein expression during myocardial remodeling. Here we investigated the role of fibulin-2 in the development of myocardial hypertrophy and fibrosis induced by continuous pressor-dosage of angiotensin II (Ang II) infusion. Both wild type (WT) and fibulin-2 null (Fbln2KO) mice developed comparable hypertension and myocardial hypertrophy by Ang II infusion. However, myocardial fibrosis with significant upregulation of collagen type I and III mRNA was only seen in WT but not in Fbln2KO mice.Transforming growth factor (TGF)-ß1 mRNA and its downstream signal, Smad2, were significantly upregulated in WT by Ang II, whereas there were no Ang II-induced changes in Flbn2KO, suggesting fibulin-2 is necessary for Ang II-induced TGF-ß signaling that induces myocardial fibrosis. To test whether fibulin-2 is sufficient for Ang II-induced TGF-ß upregulation, isolated Flbn2KO cardiac fibroblasts were treated with Ang II after transfecting with fibulin-2 expression vector or pretreating with recombinant fibulin-2 protein. Ang II-induced TGF-ß signaling in Fbln2KO cells was partially rescued by exogenous fibulin-2, suggesting that fibulin-2 is required and probably sufficient for Ang II-induced TGF-ß activation. Smad2 phosphorylation was induced just by adding recombinant fibulin-2 to KO cells, suggesting that extracellular interaction between fibulin-2 and latent TGF-ß triggered initial TGF-ß activation. Our study indicates that Ang II cannot induce TGF-ß activation without fibulin-2 and that fibulin-2 has an essential role in Ang II-induced TGF-ß signaling and subsequent myocardial fibrosis. Fibulin-2 can be considered as a critical regulator of TGF-ß that induces myocardial fibrosis.


Assuntos
Angiotensina II/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Fator de Crescimento Transformador beta1/metabolismo , Angiotensina II/administração & dosagem , Animais , Proteínas de Ligação ao Cálcio/deficiência , Proteínas de Ligação ao Cálcio/genética , Cardiomegalia/etiologia , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Modelos Animais de Doenças , Proteínas da Matriz Extracelular/deficiência , Proteínas da Matriz Extracelular/genética , Fibrose , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Cardiovasculares , Transdução de Sinais , Remodelação Ventricular
2.
Vasc Med ; 21(6): 515-519, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27235992

RESUMO

Ultrasound screening for abdominal aortic aneurysm (AAA) is recommended for male smokers >65 years of age, but screening rates remain low. If computed tomography (CT) performed for other indications could be considered adequate for screening, one-third of ultrasounds would potentially be unnecessary, and overall screening rates would be substantially higher. The objective of this study was to evaluate the sensitivity of CT imaging of the abdomen for the detection of AAA when performed for other clinical indications. We performed a retrospective study of patients eligible for AAA screening who had undergone an abdominal ultrasound as well as an abdominal CT scan for other indications within 3 years prior to that study. The primary outcome was identification of an AAA, recorded in the findings narrative or impression of the CT scan report. Of 142 patients with both a CT scan and an AAA on ultrasound, 127 (89.4%) were noted to have an AAA in the report of a CT scan performed within the 3 years prior to the ultrasound. An additional 10 films demonstrated an AAA that was not mentioned in the report. The sensitivity of pre-existing CT scans for AAA screening was 97.2% (137/141) [95% CI: 93.4-99.0%]; 123 (86.6%) of these positive findings were reported in the findings narrative and 120 (84.5%) were reported in the radiologist's final impression. The sensitivity for AAA identification in the report of a pre-existing CT scan of the abdomen performed for alternate indications appears high enough to use as a screening test. When radiologists note an AAA, they should be sure to include it in the final impression.


Assuntos
Aneurisma da Aorta Abdominal/diagnóstico por imagem , Achados Incidentais , Programas de Rastreamento/métodos , Tomografia Computadorizada por Raios X , Idoso , Feminino , Humanos , Masculino , Ohio , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Procedimentos Desnecessários
3.
Circ J ; 78(11): 2711-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25298166

RESUMO

BACKGROUND: Transforming growth factor (TGF)-ß activation is known to play a central role in progressive ventricular remodeling in advanced heart failure in animal models, but there has been no direct evidence of increased TGF-ß activity in the myocardium of patients with advanced human heart failure. METHODS AND RESULTS: Using a recently developed bioassay that measures TGF-ß bioactivity rather than TGF-ß abundance, we measured bioactive TGF-ß in human myocardium from control non-failing donors (NF), and patients with ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM). Both free and total soluble TGF-ß were significantly increased in ICM and DCM compared with NF. Free TGF-ß had an excellent correlation with phosphorylated Smad2 (R(2)=0.55, P<0.0001), a downstream marker of TGF-ß signaling. Collagen type I and type III were significantly upregulated in DCM compared with NF, consistent with histological evidence of myocardial fibrosis. Expression of fibulin-2, a positive modulator of TGF-ß, was significantly increased in DCM compared with NF, and the free TGF-ß level was correlated with fibulin-2 mRNA (R(2)=0.24, P<0.006). CONCLUSIONS: Although both free and total soluble TGF-ß are significantly increased in ICM and DCM compared with NF, the superior correlation of free TGF-ß with downstream signaling suggests that this is the most functionally relevant form. The present findings suggest that sustained TGF-ß activation in both ICM and DCM contributes to excess myocardial fibrosis.


Assuntos
Insuficiência Cardíaca/metabolismo , Proteínas Musculares/metabolismo , Miocárdio/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Adolescente , Proteínas de Ligação ao Cálcio/metabolismo , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Dilatada/patologia , Proteínas da Matriz Extracelular/metabolismo , Fibrose/metabolismo , Fibrose/patologia , Insuficiência Cardíaca/patologia , Humanos , Masculino , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/patologia , Miocárdio/patologia , Fosforilação , Proteína Smad2/metabolismo
4.
Neurotrauma Rep ; 4(1): 342-349, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37284698

RESUMO

Many studies have investigated the imaging sequelae of repetitive head trauma with mixed results, particularly with regard to the detection of intracranial white matter changes (WMCs) and cerebral microhemorrhages (CMHs) on ≤3 Tesla (T) field magnetic resonance imaging (MRI). 7T MRI, which has recently been approved for clinical use, is more sensitive at detecting lesions associated with multiple neurological diagnoses. In this study, we sought to determine whether 7T MRI would detect more WMCs and CMHs than 3T MRI in 19 professional fighters, 16 patients with single TBI, versus 82 normal healthy controls (NHCs). Fighters and patients with TBI underwent both 3T and 7T MRI; NHCs underwent either 3T (n = 61) or 7T (n = 21) MRI. Readers agreed on the presence/absence of WMCs in 88% (84 of 95) of 3T MRI studies (Cohen's kappa, 0.76) and in 93% (51 of 55) of 7T MRI studies (Cohen's kappa, 0.79). Readers agreed on the presence/absence of CMHs in 96% (91 of 95) of 3T MRI studies (Cohen's kappa, 0.76) and in 96% (54 of 56) of 7T MRI studies (Cohen's kappa, 0.88). The number of WMCs detected was greater in fighters and patients with TBI than NHCs at both 3T and 7T. Moreover, the number of WMCs was greater at 7T than at 3T for fighters, patients with TBI, and NHCs. There was no difference in the number of CMHs detected with 7T MRI versus 3T MRI or in the number of CMHs observed in fighters/patients with TBI versus NHCs. These initial findings suggest that fighters and patients with TBI may have more WMCs than NHCs and that the improved voxel size and signal-to-noise ratio at 7T may help to detect these changes. As 7T MRI becomes more prevalent clinically, larger patient populations should be studied to determine the cause of these WMCs.

5.
Cureus ; 15(12): e49992, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38058529

RESUMO

Introduction Transgender patients face substantial systemic healthcare barriers and inadequate care from providers who often demonstrate clinical gaps in the medical needs of the transgender community. Providing interventions in which affirming transgender healthcare is explored, is crucial to delivering competent transgender-patient care and building compassionate physician-patient relationships. The Northeast Pennsylvania (NEPA) Trans Health Conference was established to address the growing need for an educational forum where transgender people could voice their narratives. In this educational intervention study, changes in the knowledge, attitudes, and beliefs about the psychosocial and medical needs of the transgender community in first-year undergraduate medical students were examined pre- and post-trans health conference attendance. Materials and methods In the late spring of both 2018 and 2019, first-year medical students attended the NEPA Trans Health Conference, hosted by the Geisinger Commonwealth School of Medicine (GCSOM). Student knowledge, attitudes, and beliefs, regarding the healthcare needs of the transgender community were evaluated prior to and directly after the conference (intervention). Though the surveys shared thematic similarities, the 2018 and 2019 surveys were different and thus were not used comparatively. Results In 2018, 35.24% of first-year medical students (37/105 participants) completed both the pre- and post-survey. Overall, 62.5% (5/8) of survey items yielded significant differences. In 2019, 25.5%, of first-year medical students (28/110 participants) completed both the pre- and post-survey and 47.6% (9/21) of survey items yielded significant results. Overall, although the majority of first-year medical students displayed positive attitudes toward trans people pre-intervention, the students also demonstrated increased knowledge, empathy, and understanding of the transgender healthcare narrative post-intervention. Conclusion Providing medical students with a humanistic intervention within the medical curriculum that is focused on the transgender person, in addition to their past and present healthcare experiences, offers a bridge between academic content and providing inclusive gender-affirming healthcare to all patients.

6.
J Am Coll Radiol ; 20(2): 193-204, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35988585

RESUMO

OBJECTIVE: There is a paucity of utility and cost data regarding the launch of 3D printing in a hospital. The objective of this project is to benchmark utility and costs for radiology-based in-hospital 3D printing of anatomic models in a single, adult academic hospital. METHODS: All consecutive patients for whom 3D printed anatomic models were requested during the first year of operation were included. All 3D printing activities were documented by the 3D printing faculty and referring specialists. For patients who underwent a procedure informed by 3D printing, clinical utility was determined by the specialist who requested the model. A new metric for utility termed Anatomic Model Utility Points with range 0 (lowest utility) to 500 (highest utility) was derived from the specialist answers to Likert statements. Costs expressed in United States dollars were tallied from all 3D printing human resources and overhead. Total costs, focused costs, and outsourced costs were estimated. The specialist estimated the procedure room time saved from the 3D printed model. The time saved was converted to dollars using hospital procedure room costs. RESULTS: The 78 patients referred for 3D printed anatomic models included 11 clinical indications. For the 68 patients who had a procedure, the anatomic model utility points had an overall mean (SD) of 312 (57) per patient (range, 200-450 points). The total operation cost was $213,450. The total cost, focused costs, and outsourced costs were $2,737, $2,180, and $2,467 per model, respectively. Estimated procedure time saved had a mean (SD) of 29.9 (12.1) min (range, 0-60 min). The hospital procedure room cost per minute was $97 (theoretical $2,900 per patient saved with model). DISCUSSION: Utility and cost benchmarks for anatomic models 3D printed in a hospital can inform health care budgets. Realizing pecuniary benefit from the procedure time saved requires future research.


Assuntos
Impressão Tridimensional , Radiologia , Adulto , Humanos , Tomografia Computadorizada por Raios X , Modelos Anatômicos , Hospitais
7.
J Mol Cell Cardiol ; 52(1): 273-82, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22100229

RESUMO

Remodeling of the cardiac extracellular matrix (ECM) is an integral part of wound healing and ventricular adaptation after myocardial infarction (MI), but the underlying mechanisms remain incompletely understood. Fibulin-2 is an ECM protein upregulated during cardiac development and skin wound healing, yet mice lacking fibulin-2 do not display any identifiable phenotypic abnormalities. To investigate the effects of fibulin-2 deficiency on ECM remodeling after MI, we induced experimental MI by permanent coronary artery ligation in both fibulin-2 null and wild-type mice. Fibulin-2 expression was up-regulated at the infarct border zone of the wild-type mice. Acute myocardial tissue responses after MI, including inflammatory cell infiltration and ECM protein synthesis and deposition in the infarct border zone, were markedly attenuated in the fibulin-2 null mice. However, the fibulin-2 null mice had significantly better survival rate after MI compared to the wild-type mice as a result of less frequent cardiac rupture and preserved left ventricular function. Up-regulation of TGF-ß signaling and ECM remodeling after MI were attenuated in both ischemic and non-ischemic myocardium of the fibulin-2 null mice compared to the wild type counterparts. Increase in TGF-ß signaling in response to angiotensin II was also lessened in cardiac fibroblasts isolated from the fibulin-2 null mice. The studies provide the first evidence that absence of fibulin-2 results in decreased up-regulation of TGF-ß signaling after MI and protects against ventricular dysfunction, suggesting that fibulin-2 may be a potential therapeutic target for attenuating the progression of ventricular remodeling.


Assuntos
Proteínas de Ligação ao Cálcio/deficiência , Proteínas da Matriz Extracelular/deficiência , Infarto do Miocárdio/genética , Remodelação Ventricular/genética , Angiotensina II/farmacologia , Animais , Proteínas de Ligação ao Cálcio/genética , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/mortalidade , Miocárdio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Função Ventricular Esquerda , Cicatrização/genética
8.
Radiol Case Rep ; 17(2): 350-354, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34887974

RESUMO

In this case report, a 23-year-old female presented to the Emergency Department with complaints of abdominal pain, weight loss, progressive headaches, and an episode of seizure-like activity. Computerized tomography abdomen/pelvis revealed multilobulated ovarian masses and scattered peritoneal thickening. A brain Magnetic resonance imaging was ordered and demonstrated a peripherally enhancing intracranial mass. The brain lesion was resected and pathology revealed necrotizing granulomatous inflammation. Cultures were positive for acid fast bacilli. The patient was diagnosed with tuberculosis and treated with multidrug therapy. Upon further questioning, the patient had recently traveled to a tuberculosis endemic region. This case highlights the importance of an in-depth history and physical exam as a means to a more complete differential diagnosis considering the age of the patient and the findings on imaging.

9.
J Cancer Educ ; 26(2): 285-93, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20640779

RESUMO

While patient barriers to colorectal cancer (CRC) screening have been identified, how well this knowledge is utilized during the patient-physician interaction is not fully understood. This study aims to assess among primary care physicians the degree of consensus between perceived and actual patients' CRC screening decision-making influential factors. During 2004-2006, 30 patients were interviewed to identify factors influencing screening decisions and 66 physicians were interviewed to understand what factors they thought were important to patients. The factors were categorized using the PRECEDE-PROCEED framework, and perspectives were compared. The researchers found little consensus on CRC screening decision-making influential factors between family practitioners, general internists, and patients. The recommendations to reach consensus are provided on the individual (e.g., updating the contents of a physician's screening recommendation to proactively address patients' decision-making needs) and population (e.g., providing cross-cultural training to medical students enabling them to better understand their patients) levels.


Assuntos
Neoplasias Colorretais/diagnóstico , Tomada de Decisões , Detecção Precoce de Câncer/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Papel do Médico , Padrões de Prática Médica , Adulto , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
10.
Brain Cogn ; 71(1): 14-9, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19346049

RESUMO

This research aimed to investigate the time course effect of a moderate steady-state exercise session on response execution and response inhibition using a stop-task paradigm. Ten participants performed a stop-signal task whilst cycling at a carefully controlled workload intensity (40% of maximal aerobic power), immediately following exercise and 30min after exercise cessation. Results showed that moderate exercise enhances a subjects' ability to execute responses under time pressure (shorter Go reaction time, RT without a change in accuracy) but also enhances a subjects' ability to withhold ongoing motor responses (shorter stop-signal RT). The present outcomes reveal that the beneficial effect of exercise is neither limited to motor response tasks, nor to cognitive tasks performed during exercise. Beneficial effects of exercise remain present on both response execution and response inhibition performance for up to 52min after exercise cessation.


Assuntos
Cognição , Exercício Físico/psicologia , Desempenho Psicomotor , Análise de Variância , Feminino , Humanos , Masculino , Atividade Motora , Testes Neuropsicológicos , Tempo de Reação , Análise e Desempenho de Tarefas , Fatores de Tempo , Adulto Jovem
11.
Med Educ ; 42(8): 771-7, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18715476

RESUMO

CONTEXT: Teaching and evaluating professionalism remain important issues in medical education. However, two factors hinder attempts to integrate curricular elements addressing professionalism into medical school training: there is no common definition of medical professionalism used across medical education, and there is no commonly accepted theoretical model upon which to integrate professionalism into the curriculum. OBJECTIVES: This paper proposes a definition of professionalism, examines this definition in the context of some of the previous definitions of professionalism and connects this definition to the attitudinal roots of professionalism. The problems described above bring uncertainty about the best content and methods with which to teach professionalism in medical education. Although various aspects of professionalism have been incorporated into medical school curricula, content, teaching and evaluation remain controversial. We suggest that intervening variables, which may augment or interfere with medical students' implementation of professionalism knowledge, skills and, therefore, attitudes, may go unaddressed. DISCUSSION: We offer a model based on the theory of planned behaviour (TPB), which describes the relationships of attitudes, social norms and perceived behavioural control with behaviour. It has been used to predict a wide range of behaviours, including doctor professional behaviours. Therefore, we propose an educational model that expands the TPB as an organisational framework that can integrate professionalism training into medical education. We conclude with a discussion about the implications of using this model to transform medical school curricula to develop positive professionalism attitudes, alter the professionalism social norms of the medical school and increase students' perceived control over their behaviours.


Assuntos
Educação de Graduação em Medicina/métodos , Competência Profissional/normas , Ensino/métodos , Atitude do Pessoal de Saúde , Comportamento , Currículo , Humanos , Percepção
12.
J Gen Intern Med ; 22(10): 1467-9, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17710501

RESUMO

OBJECTIVE: The purpose of this study was to identify decision heuristics utilized by primary care physicians in formulating colorectal cancer screening recommendations. DESIGN: Qualitative research using in-depth semi-structured interviews. PARTICIPANTS: We interviewed 66 primary care internists and family physicians evenly drawn from academic and community practices. A majority of physicians were male, and almost all were white, non-Hispanic. APPROACH: Three researchers independently reviewed each transcript to determine the physician's decision criteria and developed decision trees. Final trees were developed by consensus. The constant comparative methodology was used to define the categories. RESULTS: Physicians were found to use 1 of 4 heuristics ("age 50," "age 50, if family history, then earlier," "age 50, if family history, then screen at age 40," or "age 50, if family history, then adjust relative to reference case") for the timing recommendation and 5 heuristics ["fecal occult blood test" (FOBT), "colonoscopy," "if not colonoscopy, then...," "FOBT and another test," and "a choice between options"] for the type decision. No connection was found between timing and screening type heuristics. CONCLUSIONS: We found evidence of heuristic use. Further research is needed to determine the potential impact on quality of care.


Assuntos
Neoplasias Colorretais/prevenção & controle , Tomada de Decisões , Programas de Rastreamento/métodos , Médicos de Família , Adulto , Atitude Frente a Saúde , Competência Clínica , Colonoscopia/estatística & dados numéricos , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Sangue Oculto , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normas , Padrões de Prática Médica/tendências , Sensibilidade e Especificidade , Inquéritos e Questionários
13.
Patient Educ Couns ; 66(1): 43-50, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17098393

RESUMO

OBJECTIVE: The purpose of this research was to examine the content of physicians' colorectal cancer screening recommendations. More specifically, using the framework of informed decision making synthesized by Braddock and colleagues, we conducted a qualitative study of the content of recommendations to describe how physicians are currently presenting this information to patients. METHODS: We conducted semi-structured interviews with 65 primary care physicians. We analyzed responses to a question designed to elicit how the physicians typically communicate their recommendation. RESULTS: Almost all of the physicians (98.5%) addressed the "nature of decision" element. A majority of physicians discussed "uncertainties associated with the decision" (67.7%). Fewer physicians covered "the patient's role in decision making" (33.8%), "risks and benefits" (16.9%), "alternatives" (10.8%), "assessment of patient understanding" (6.2%), or "exploration of patient's preferences" (1.5%). CONCLUSION: We propose that the content of the colorectal screening recommendation is a critical determinant to whether a patient undergoes screening. Our examination of physician recommendations yielded mixed results, and the deficiencies identified opportunities for improvement. PRACTICE IMPLICATIONS: We suggest primary care physicians clarify that screening is meant for those who are asymptotic, present tangible and intangible benefits and risks, as well as make a primary recommendation, and, if needed, a "compromise" recommendation, in order to increase screening utilization.


Assuntos
Neoplasias Colorretais/diagnóstico , Comunicação , Tomada de Decisões , Programas de Rastreamento , Educação de Pacientes como Assunto/organização & administração , Médicos de Família/psicologia , Adulto , Atitude do Pessoal de Saúde , Atitude Frente a Saúde , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Diretrizes para o Planejamento em Saúde , Humanos , Consentimento Livre e Esclarecido , Kentucky , Masculino , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Pessoa de Meia-Idade , Participação do Paciente/métodos , Participação do Paciente/psicologia , Seleção de Pacientes , Relações Médico-Paciente , Médicos de Família/organização & administração , Guias de Prática Clínica como Assunto , Medição de Risco , Inquéritos e Questionários , Incerteza
14.
Endocrinology ; 143(6): 2093-105, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12021174

RESUMO

We previously demonstrated that 1) treatment of Noble rats for 16 wk with testosterone (T) and estradiol-17 beta (E2) led to 100% incidence of dorsolateral prostate (DLP) dysplasia and hyperprolactinemia and 2) blockade of PRL release with bromocriptine cotreatment significantly lowered the incidence of DLP dysplasia. In the current study, we sought to determine whether E2 exerts direct effects, independent of PRL, in this model system. The pure antiestrogen ICI 182,780 (ICI), reported to have no effect on PRL release in female rats, was administered biweekly to T + E2-treated rats at 3 mg/kg body weight. ICI cotreatment completely prevented DLP dysplasia development but it also blocked hyperprolactinemia in the dual hormone-treated rats. Gene profiling with an 1185 gene rat cDNA array identified approximately 100 genes displaying > or = 3-fold changes in rat lateral prostates (LPs) following T + E2 treatment. Significantly more genes were up-regulated (77) than down-regulated (14), reflecting cellular/molecular changes associated with enhanced cell proliferation, DNA damage, heightened protein and RNA synthesis, increased energy metabolism, and activation of several proto-oncogenes and intracellular signaling pathways. Post hoc analyses, using quantitative real-time RT-PCR, corroborated differential expression of eight genes, exhibiting three different patterns of altered expression. Genes encoding the early growth response protein 1 and metalloendopeptidase meprin beta-subunit were similarly altered in T + E2- and T + E2 + ICI-treated animals when compared with untreated controls. In contrast, transcripts of fos-related antigen-2, growth arrest and DNA damage-inducible protein-45, and signal transducer and activator of transcription-3 were significantly increased in the LPs of T + E2-treated animals, but the increases were reversed by cotreatment with ICI. Differential expression of fos-related antigen-2 and growth arrest and DNA damage-inducible protein-45 were further confirmed at the protein level by immunohistochemistry. Lastly, levels of A-RAF, VIP-1 receptor, and calpastatin mRNA were distinctly lessen in rat LPs under T + E2 influence, but rebound with ICI cotreatment. In conclusion, our findings further implicated pituitary PRL in the induction of dysplasia in rat LP. Gene profiling provided clues that molecular events related to enhancement of cell proliferation, DNA damage, and activation of proto-oncogenes and transforming factors may be causally linked to the genesis of LP dysplasia in this rat model.


Assuntos
Proteínas de Arabidopsis , Estradiol/análogos & derivados , Estradiol/farmacologia , Antagonistas de Estrogênios/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas Imediatamente Precoces , Hiperplasia Prostática/genética , Testosterona , Adenosina Trifosfatases , Animais , Proteínas de Ligação ao Cálcio/biossíntese , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/genética , Proteína 1 de Resposta de Crescimento Precoce , Fulvestranto , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Katanina , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas de Plantas/biossíntese , Proteínas de Plantas/genética , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/prevenção & controle , Biossíntese de Proteínas , Proteínas/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Radioimunoensaio , Ratos , Receptores de Peptídeo Intestinal Vasoativo/biossíntese , Receptores de Peptídeo Intestinal Vasoativo/genética , Receptores Tipo I de Polipeptídeo Intestinal Vasoativo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição STAT3 , Transativadores/biossíntese , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética
15.
Med Sci Sports Exerc ; 46(3): 630-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23924921

RESUMO

PURPOSE: This study aimed to investigate the influence of an acute bout of moderate exercise and examine the potential lasting improvements over time in young and old adults within the same experimental paradigm over a 2-h testing period. The study was designed to assess the efficiency of selective control and the propensity to make fast impulsive reactions through the analyses of the percentage of correct responses (CAF) and the magnitude of the interference effect (delta curve) as a function of the latency of the response. METHODS: Twelve young (23 ± 2 yr) and 12 old (63 ± 2 yr) volunteers performed the Simon task while cycling (30 min of cycling at 65% of age-predicted HRmax) and after exercise cessation (post 5 min, post 35 min, and post 65 min). RESULTS: Results showed that exercise did not alter cognitive control. The benefit on reaction time performance was evident for both age groups and persisted after cessation for 15-20 min. Distributional analyses showed that younger people have a higher propensity to commit impulsive errors during exercise, which was not evident in older adults. Older adults adopted more cautious strategies, especially when the risk to commit an error was elevated. Despite the larger mean interference effect compared to younger adults, the pattern of the delta curves attests to the existence of an efficient cognitive control in older people. CONCLUSIONS: This study illustrates the effectiveness of distributional analyses and supports the idea that exercise-induced facilitation on cognitive performance can be realized across the lifespan. Future investigations should explore whether accumulated bouts of acute exercise could display an aggregate cognitive benefit, which may significantly affect independent functioning in older adults.


Assuntos
Envelhecimento/psicologia , Cognição , Exercício Físico/psicologia , Testes de Inteligência , Adulto , Idoso , Ciclismo , França , Humanos , Pessoa de Meia-Idade , Desempenho Psicomotor , Adulto Jovem
17.
BMC Res Notes ; 5: 636, 2012 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-23151377

RESUMO

BACKGROUND: Transforming growth factor-ß (TGF-ß) is a multi-factorial peptide growth factor that has a vital role in the regulation of cell growth, differentiation, inflammation, and tissue repair. Quantification of biologically active TGF-ß levels in tissues is crucial to illustrate mechanisms involved in various physiological and pathological processes, but direct measurement of bioactive TGF-ß level in the tissue has been hampered by lack of reliable methods. Here, we introduced mink lung epithelial cell bioassay to quantify both active and total TGF-ß levels in serum and protein lysates from solid organs in the mouse model. FINDINGS: Mink lung epithelial cells were stably transfected with plasminogen activator inhibitor-1 promoter/luciferase construct, in which bioactive TGF-ß level was represented by luciferase activity. Serum total TGF-ß levels were comparable between the bioassay and enzyme-linked immunosorbent assay (ELISA), but active TGF-ß levels measured by ELISA were significantly lower than those obtained by the bioassay. Active and total TGF-ß levels in the solid organs including heart, liver, and kidney were also measured. Total TGF-ß levels were relatively comparable among these organs, but active TGF-ß levels were slightly higher in hearts and kidneys than in livers. Positive luciferase activities in the bioassay were almost completely inhibited by adding pan-TGF-ß neutralizing antibodies, suggesting its high specificity to bioactive TGF-ß. We also measured myocardial TGF-ß levels after myocardial infarction and sham control by the bioassay, and compared the values with those obtained by ELISA. The bioassay demonstrated that both active and total tissue TGF-ß levels were significantly higher in post-myocardial infarction than in sham myocardium. ELISA was markedly less sensitive in detecting both active and total TGF-ß levels than our bioassay and failed to show any statistically significant difference in TGF-ß levels between myocardial infarction and sham myocardium. CONCLUSIONS: Our data suggested that the bioassay was significantly more sensitive than ELISA in detecting active TGF-ß in serum and both active and total TGF-ß in solid organ tissues. The bioassay will be useful in investigating TGF-ß profile in various solid organs in physiological and pathological conditions.


Assuntos
Bioensaio/normas , Infarto do Miocárdio/sangue , Miocárdio/metabolismo , Fator de Crescimento Transformador beta/análise , Animais , Calibragem , Ensaio de Imunoadsorção Enzimática , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Genes Reporter , Rim/citologia , Rim/metabolismo , Fígado/citologia , Fígado/metabolismo , Luciferases , Pulmão/citologia , Pulmão/metabolismo , Camundongos , Vison , Infarto do Miocárdio/patologia , Miocárdio/patologia , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Sensibilidade e Especificidade , Transfecção , Fator de Crescimento Transformador beta/biossíntese
20.
Public Health Nutr ; 12(1): 51-8, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18312704

RESUMO

OBJECTIVE: To study patterns of phytosterol intakes in the Irish population from enriched sources. DESIGN: An interview-assisted questionnaire, which recorded information on sociodemographics, product types, intake amounts and patterns of intake. Independent samples t tests, one-way ANOVA and cross-tabulations were used to establish significant relationships between groups of variables. The top tertile of phytosterol intakes was also calculated. SETTING: Point-of-purchase of phytosterol-enriched products in Irish supermarkets. SUBJECTS: Four hundred and sixty-eight consumers (186 men and 282 women) of phytosterol-enriched foods. RESULTS: The mean phytosterol intake from enriched sources for the sample population was 2.45 g/d. Men had greater intakes than women (2.71 g/d v. 2.29 g/d, respectively). A total of 62 % of consumers were unaware of the importance of consuming fruit and vegetables while taking these products. The majority of respondents reported that they had high cholesterol (61 %) and 22 % of consumers also took cholesterol-lowering medication (statins). In total, 23 % had phytosterol intakes >3.0 g/d and the majority of consumers (58 %) had been consuming these products for >1 year. The mean intake for respondents with phytosterol intakes >3.0 g/d was 4.1 g/d and 74 % of this subgroup had been consuming these products for >1 year. CONCLUSION: In general, phytosterol intakes are within efficacious levels in the Irish population. However, there appears to be a subgroup that has been consuming these products at intakes greater than current recommendations for >1 year.


Assuntos
Dieta/estatística & dados numéricos , Alimentos Fortificados/estatística & dados numéricos , Fitosteróis/administração & dosagem , Adulto , Análise de Variância , Feminino , Humanos , Hipercolesterolemia/epidemiologia , Irlanda , Masculino , Inquéritos e Questionários
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