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1.
Vet Clin Pathol ; 52(3): 396-401, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37369632

RESUMO

BACKGROUND: Cellular deterioration occurs with blood sample aging, impacting white blood cell (WBC) identification and differential accuracy. This may be exacerbated in samples from patients experiencing inflammation. Previously, bovine serum albumin (BSA) has been shown to improve cellular preservation of blood and other samples, but the effect on cell preservation in canine blood has not been assessed. OBJECTIVES: We aimed to determine the effects of BSA on neutrophil nuclear area when added to potassium ethylene diamine tetra-acetic acid (K3 -EDTA)-anticoagulated canine blood prior to blood smear preparation. We evaluated the impact of inflammatory leukograms, sample storage temperatures (4° and 20°C), and time on outcomes. MATERIALS AND METHODS: Canine K3 -EDTA-anticoagulated blood samples stored at 4° and 20°C were used from unique patients, 10 with and 10 without inflammatory leukograms. Blood smears were prepared from aliquots with or without the addition of 22% BSA at 0, 4, 8, 24, 48, and 72 h. The nuclear area was measured for 25 randomly selected neutrophils per slide using Fiji software. Mixed-effect linear regression modeling was performed (significance: P < 0.05). RESULTS: Nuclear area increased over time with and without added BSA. Both sample storage temperatures and the presence or absence of an inflammatory leukogram significantly impacted neutrophil nuclear area. Samples with added BSA had slightly higher predicted nuclear areas than those without BSA, but this difference was not statistically significant. CONCLUSIONS: BSA did not significantly impact neutrophil nuclear area and did not improve neutrophil preservation in canine blood samples.


Assuntos
Neutrófilos , Soroalbumina Bovina , Animais , Cães , Soroalbumina Bovina/farmacologia , Ácido Edético/farmacologia , Preservação Biológica/veterinária , Leucócitos
2.
Hum Factors ; 64(3): 579-588, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-32930010

RESUMO

OBJECTIVE: The purpose of this study was to examine how intensity of wave motions affects the performance of a simulated maritime search and rescue (SAR) task. BACKGROUND: Maritime SAR is a critical maritime occupation; however, the effect of wave motion intensity on worker performance is unknown. METHODS: Twenty-four participants (12 male, 12 female) performed a simulated search and rescue task on a six-degree-of-freedom motion platform in two conditions that differed in motion intensity (low and high). Task performance, electromyography (EMG), and number of compensatory steps taken by the individual were examined. RESULTS: As magnitude of simulated motion increased, performance in the SAR task decreased, and was accompanied by increases in lower limb muscle activation and number of steps taken. CONCLUSIONS: Performance of an SAR task and balance control may be impeded by high-magnitude vessel motions. APPLICATION: This research has the potential to be used by maritime engineers, occupational health and safety professionals, and ergonomists to improve worker safety and performance for SAR operators.


Assuntos
Saúde Ocupacional , Trabalho de Resgate , Eletromiografia , Feminino , Humanos , Masculino , Movimento (Física) , Análise e Desempenho de Tarefas
3.
Reprod Sci ; 28(4): 1200-1215, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33415648

RESUMO

Epidemiological evidence suggests that normal pregnancy in women is associated with decreased cardiovascular risk in later life. Clinical studies have provided evidence that alterations in vascular function and structure are detectable long after delivery. To understand these findings, we examined mesenteric artery reactivity at both early (3 days and 2-4 weeks) and late (12 weeks) postpartum (PP) time points in relation to late pregnancy (LP) and lactation. Vessels from virgin controls, LP, PP, and nursing and non-nursing mothers were tested for responses to phenylephrine (PE), high potassium solutions (high K+), and acetylcholine (ACh). Passive arterial distensibility, vessel dimensions, and collagen and elastin content were evaluated for the studied groups. We observed that (1) there was a significant inhibition of vascular reactivity to PE in LP, 3 days and 2 weeks PP vessels that returned to pre-pregnancy levels at 4 and 12 weeks PP; (2) inhibition of NO production in PP vessels restored PE-induced constriction to pre-pregnancy levels; (3) vasodilator responses to ACh were similar at all PP periods; (4) LP and early PP was associated with a persistent increase in arterial distensibility that correlates with a PP-induced reduction in wall collagen, and regressed to pre-conception levels at 12 weeks PP; (5) vessels from non-nursing PP mice demonstrated an increased PE reactivity, diminished responses to ACh, and reduced distensibility compared to breastfeeding mice. These studies provide a timeframe for mesenteric artery adaptations that occur during pregnancy and extend to the PP period, but which may be modified by PP events.


Assuntos
Lactação/fisiologia , Artérias Mesentéricas/efeitos dos fármacos , Acetilcolina/farmacologia , Animais , Colágeno/metabolismo , Elastina/metabolismo , Feminino , Artérias Mesentéricas/fisiologia , Camundongos , Fenilefrina/farmacologia , Período Pós-Parto , Potássio/farmacologia , Gravidez , Vasoconstritores/farmacologia , Vasodilatadores/farmacologia
4.
Cureus ; 12(5): e8377, 2020 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-32626621

RESUMO

Introduction Urinary catheter insertion is a mandatory procedure taught during medical school. It is imperative that learners are provided the opportunity to practice the procedure, as an improper catheterization technique can result in urethral trauma and contribute to urinary tract infections. Simulation training offers the advantage of avoiding patient harm while allowing learners to feel comfortable to learn from their mistakes, resulting in increased user confidenceand shortening the learning curve for basic procedures. 3D-printed simulation models are anatomically accurate, low-cost, reusable, and effective for teaching basic procedural skills.This study aims to assess the self-rated effectiveness of the 3D model in increasing student confidence and preparedness. Methods Preclerkship undergraduate medical students (n=64) participated in procedural skills training sessions using the 3D-printed model. The students were provided with didactic teaching from a urologist, a hands-on demonstration, and then allowed to practice the procedure using the 3D model. Students were subsequently asked to complete a Likert-type survey to evaluate their experience and the 3D model as an educational tool. Results Respondents felt that the 3D-printed model allowed for the realistic and accurate performance of a urinary catheterization procedure, allowing students to increase their confidence, competence, and knowledge of the technique. Student responses for increasing competence were rated as an average of 4.48±0.62 (where 1 is "not at all effective" and 5 is "very effective"), confidence was rated as 4.40±0.71, and preparedness was reported as 4.15±0.76. Overall, the reported value as a training tool resulted in an average score of 4.62±0.58 (where 1 is "not at all relevant" and 5 is "very relevant"). Conclusions Preclerkship undergraduate medical students found the 3D-printed male catheter insertion model to be a useful learning tool with accurate anatomical representations and technical qualities. The 3D-printed model can be beneficial for increasing learner confidence and preparedness when completing a catheter insertion, allowing for the opportunity to practice on a low-cost, accessible simulator.

5.
Hypertension ; 76(1): 226-235, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32418498

RESUMO

Leptomeningeal anastomoses (LMAs) are pial collaterals that perfuse the penumbra and important for stroke outcome. We previously showed LMAs from SHRs (spontaneously hypertensive rats) were vasoconstricted compared with normotensive Wistar rats. Here, we investigated mechanisms by which hypertension causes LMA vasoconstriction. SHRs were treated with the ACE (angiotensin-converting enzyme) inhibitor captopril, an Ang II (angiotensin II)-independent antihypertensive agent hydralazine, or vehicle for 5 weeks in drinking water (n=8/group). A group of Wistar rats (n=8) had regular drinking water served as controls. Blood pressure was measured twice weekly by tail-cuff. LMAs were isolated and studied under pressurized conditions. Vasoreactivity of LMAs, including myogenic responses, reactivity to Rho-kinase inhibitor Y-27632, and nitric oxide were measured. Both captopril and hydralazine lowered blood pressure in SHRs similar to Wistar. However, only captopril normalized LMA increased tone compared with untreated SHRs (15±2% versus 50±3%; P<0.01) that was similar to Wistar (16±2%) but not hydralazine (38±6%; P>0.05). Vasodilatory response of LMAs to Y-27632 was impaired in SHRs compared with Wistar (28±3% versus 81±4%; P<0.01) that was restored by captopril (84±5%; P<0.01) and partially hydralazine (59±4%). LMAs from all groups constricted similarly to NOS (NO synthase) inhibition; however, the vasodilatory response of LMAs to the nitric oxide donor sodium nitroprusside was impaired in SHRs compared with Wistar rats (29±4% versus 80±2%; P<0.01) that was restored by captopril (84±4%; P<0.01), not hydralazine (38±8%; P>0.05). These results suggest that ACE inhibition during chronic hypertension reversed vascular dysfunction and hyperconstriction of LMAs that could improve stroke outcome by increasing collateral perfusion.


Assuntos
Angiotensina II/fisiologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Captopril/farmacologia , Circulação Colateral/efeitos dos fármacos , Hidralazina/farmacologia , Hipertensão/tratamento farmacológico , Pia-Máter/irrigação sanguínea , Vasoconstrição/efeitos dos fármacos , Vasodilatadores/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Benzimidazóis/farmacologia , Compostos de Bifenilo/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Captopril/uso terapêutico , Doença Crônica , Hidralazina/uso terapêutico , Hipertensão/genética , Hipertensão/fisiopatologia , Masculino , Distribuição Aleatória , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , Receptor Tipo 1 de Angiotensina/biossíntese , Receptor Tipo 1 de Angiotensina/genética , Tetrazóis/farmacologia , Sistema Vasomotor/efeitos dos fármacos , Quinases Associadas a rho/fisiologia
6.
Cureus ; 12(1): e6612, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-32064192

RESUMO

Suturing is an essential procedural skill that medical students are expected to be competent in before they graduate medical school; however, there is often a lack of suturing instruction and practice in undergraduate medicine curriculums. Silicone suturing task trainers created from 3D printed molds can help address this gap in medical education by improving student's manual skills before they perform procedures on real patients upon graduation. Commercially available suture task trainers on the market today lack validation from medical learners; therefore, this study aimed to evaluate the perceived efficacy of a silicone skin suture task trainer created from a 3D printed mold using input from novice medical trainees. A silicone task trainer created by MUN Med 3D was used to teach suturing during two surgery interest group skill development sessions. At the end of the sessions, 38 medical students completed a product evaluation survey that assessed the perceived educational efficacy of the suturing task trainer. Overall, the feedback received from the participants was positive and supported the use of silicone suturing task trainers in undergraduate medicine curriculums.

7.
Cureus ; 11(4): e4373, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-31218138

RESUMO

Patients with a traumatic head injury (THI) require immediate surgical intervention, as rapidly expanding intracranial hematomas can be imminently life-threatening, not permitting transfer time to neurosurgical care in a tertiary care center. In rural and remote areas, where neurosurgeons may not be readily available, surgical intervention by Community General Surgeons (CGS) may be required. Currently, the CGS in Newfoundland and Labrador (NL) do not have access to, or have experience training with, an emergent burr hole/craniotomy (EBHC) simulator. One of the barriers is the availability of inexpensive and reliable simulators to practice these skills. Therefore, a low-cost, three-dimensional (3D) printed EBHC simulator was designed and 3D-printed by MUN Med 3D (St John's, NL). The aim of this technical report is to assess the need for such simulator in rural and remote healthcare centers and report on the iterative development of the EBHC simulator. The 3D-printed EBHC simulator developed by MUN Med 3D was utilized during a general surgery workshop at the 26th Annual Rural and Remote Medicine Conference in St. John's, NL. A total of six 3D-printed EBHC simulators were provided for the hour and a half workshop. At the end of the workshop, 16 participants were asked to provide feedback on the need for this simulator in their rural or remote environment as well as feedback on the physical attributes. The feedback received from the participants was overall positive, informative, and supported the need for the 3D-printed EBHC simulator.

8.
Stroke ; 49(8): 1969-1976, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29991657

RESUMO

Background and Purpose- Aging and hypertension, comorbidities prevalent in the stroke population, are associated with poor collateral status and worsened stroke outcome. However, underlying mechanisms by which these conditions affect stroke outcome are not clear. We studied the role of PAI (plasminogen activator inhibitor)-1 that is increased in aging and hypertension on brain and vascular expression of inflammatory factors and perfusion that may contribute to worse stroke outcomes. Methods- Aged (≈50 weeks) and young (≈18 weeks) spontaneously hypertensive rats (SHR) were subjected to ischemia by middle cerebral artery occlusion (2 hours) and reperfusion (2 hours) with or without treatment with the PAI-1 inhibitor TM5441. Changes in middle cerebral artery and collateral perfusion territories were measured by multisite laser Doppler. Reactivity to TM5441 was studied using isolated and pressurized leptomeningeal anastomotic arterioles. Brain injury was determined by 2,3,5-triphenyltetrazolium staining and quantitative immunohistochemistry of amyloid-ß-42, PAI-1, and hemoglobin. Circulating inflammatory factors were measured by ELISA. Results- Changes in cerebral blood flow during middle cerebral artery occlusion were similar between groups, with both having poor collateral perfusion and incomplete reperfusion. However, aged SHR had greater brain injury versus young (41±2 versus 23±2%, P<0.05) as well as increased brain deposition of amyloid-ß-42 and circulating oxLDL (oxidized low-density lipoprotein). Erythrocyte aggregation and hemorrhage within the injured brain was observed in 50% of aged but no young SHR, with increased circulating PAI-1 in this subgroup of aged SHR (16±3 versus 6±2 ng/mL, P<0.05). PAI-1 inhibition with TM5441 improved brain injury but did not affect hemorrhage. TM5441 increased collateral perfusion by 38±7% and dilated leptomeningeal anastomotic arterioles by 44±10%, which was abolished by nitric oxide synthase inhibition. Conclusions- Increased injury in aged SHR seemed to be related to poor collateral perfusion, hemorrhagic transformation, increased amyloid-ß-42, and oxidative stress. PAI-1 inhibition reduced infarction in both groups of SHR that possibly due, in part, to increased collateral perfusion.


Assuntos
Envelhecimento/metabolismo , Isquemia Encefálica/metabolismo , Circulação Cerebrovascular/fisiologia , Circulação Colateral/fisiologia , Hipertensão/metabolismo , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Acidente Vascular Cerebral/metabolismo , Envelhecimento/efeitos dos fármacos , Animais , Encéfalo/irrigação sanguínea , Encéfalo/efeitos dos fármacos , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/fisiopatologia , Circulação Cerebrovascular/efeitos dos fármacos , Circulação Colateral/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , Piperazinas/farmacologia , Piperazinas/uso terapêutico , Ratos , Ratos Endogâmicos SHR , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/fisiopatologia , para-Aminobenzoatos/farmacologia , para-Aminobenzoatos/uso terapêutico
9.
Transl Stroke Res ; 9(5): 499-505, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29313240

RESUMO

Although used extensively in stroke research, there is limited knowledge of how 2, 3, 5-triphenyltetrazolium chloride (TTC)-treated rat brain sections are altered and if they can be used for immunohistochemical quantification after staining with TTC. In the present study, we hypothesized that TTC treatment (TTC+) would not interfere with collagen IV immunohistochemical staining compared with non-TTC-treated (TTC-) brain slices. We further hypothesized that there would be no difference in autofluorescence or nonspecific secondary antibody fluorescence between TTC+ and TTC- brain slices. Coronal brain sections of male Wistar rats (n = 5/group) were either treated with TTC or not after middle cerebral artery occlusion or sham surgery, and processed for immunohistochemical staining with mouse anti-collagen IV as the primary antibody, and goat anti-IgM as the secondary antibody. Four images were taken in the cerebral cortex of the contralateral side of infarction in each brain slice using an Olympus BX50 fluorescence microscope, and average intensity of the entire image was quantified using the Metamorph software. Compared with TTC- brain slices, TTC+ brain slices showed a significantly lower autofluorescence (P < 0.05), but was unchanged for nonspecific secondary antibody fluorescence. In addition, TTC+ brain slices had similar collagen IV staining intensity compared with TTC- brain slices. These results demonstrate that TTC+ brain slices are usable for immunohistochemical quantification.


Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Colágeno Tipo IV/metabolismo , Corantes/farmacologia , Acidente Vascular Cerebral/patologia , Sais de Tetrazólio/farmacologia , Animais , Encéfalo/diagnóstico por imagem , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar
10.
Cureus ; 10(12): e3764, 2018 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-30868000

RESUMO

The purpose of this technical report was two-fold. First was to describe the concept, development and initial implementation of a three-dimensional (3D) printing network focussed on manufacturing simulators and simple devices necessary to the functioning of rural hospital and clinics. Second was to describe the design, fabrication and user-based evaluation of a cost-effective tongue depressor dispenser. The initial successful setup and implementation of the 3D printing network were modelled using four of the five implementation constructs derived from the Consolidated Framework for Implementation Research (CFIR). The 3D printing of the tongue depressor dispenser was found to be an effective and economic initiative. Without considering the initial design costs, the materials costs were estimated at $6 Canadian per dispenser. After installation of the dispenser in a busy emergency department, hospital leadership and staff viewed it as a safer option to the current dispense, and more affordable.

11.
Physiol Rep ; 5(20)2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29066596

RESUMO

Advanced glycation end-products (AGEs) play a role in the pathophysiology of diabetes mellitus (DM) and possibly hypertension (HTN). In experimental DM, AGEs accumulate in myocardium. Little is known about AGEs in human myocardium. We quantified abundance, localization, and functional correlates of the AGE carboxymethyl lysine (CML) in left ventricular (LV) myocardium from patients undergoing coronary bypass grafting (CBG). Immunoelectron microscopy was used to quantify CML in epicardial biopsies from 98 patients (71 M, 27 F) with HTN, HTN + DM or neither (controls), all with normal LV ejection fraction. Myofilament contraction-relaxation function was measured in demembranated myocardial strips. Echocardiography was used to quantify LV structure and function. We found that CML was abundant within cardiomyocytes, but minimally associated with extracellular collagen. CML counts/µm2 were 14.7% higher in mitochondria than the rest of the cytoplasm (P < 0.001). There were no significant sex or diagnostic group differences in CML counts [controls 45.6 ± 3.6/µm2 (±SEM), HTN 45.8 ± 3.6/µm2, HTN + DM 49.3 ± 6.2/µm2; P = 0.85] and no significant correlations between CML counts and age, HgbA1c or myofilament function indexes. However, left atrial volume was significantly correlated with CML counts (r = 0.41, P = 0.004). We conclude that in CBG patients CML is abundant within cardiomyocytes but minimally associated with collagen, suggesting that AGEs do not directly modify the stiffness of myocardial collagen. Coexistent HTN or HTN + DM do not significantly influence CML abundance. The correlation of CML counts with LAV suggests an influence on diastolic function independent of HTN, DM or sex whose mechanism remains to be determined.


Assuntos
Doença das Coronárias/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Lisina/análogos & derivados , Miócitos Cardíacos/metabolismo , Idoso , Estudos de Casos e Controles , Colágeno/metabolismo , Feminino , Ventrículos do Coração/metabolismo , Humanos , Lisina/metabolismo , Masculino , Pessoa de Meia-Idade , Contração Miocárdica , Miócitos Cardíacos/fisiologia , Miócitos Cardíacos/ultraestrutura , Função Ventricular
13.
Can J Diet Pract Res ; 78(2): 59-65, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28145745

RESUMO

PURPOSE: To compare docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and fish intake of pregnant women at 30 weeks of gestation to current recommendations and to determine the factors associated with omega-3 (ω-3) intake. METHODS: A food frequency questionnaire was completed by 54 women (54/131 = 41%) at 30 ± 0.8 weeks gestation. Supplement intake, sociodemographic characteristics, and ω-3 food habits were evaluated. RESULTS: Among this high socioeconomic status (SES) group, 66.7% and 64.8% met the Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO) recommendation of 200 mg/d DHA and 300 mg/d DHA + EPA, respectively, and only 48.1% met the Academy of Nutrition and Dietetics (Academy) recommendation of 500 mg/d DHA + EPA. Eighteen of the 54 women took a ω-3 supplement during the third trimester. This significantly improved their total intake to meet the FAO/WHO (88.9% ≥200 mg/d DHA and 94.4% ≥300 mg/d DHA + EPA) and the Academy (77.8% ≥500 mg/d DHA + EPA) recommendations. Among nonsupplement users (36/54), 50% met the FAO/WHO recommendations and only 33.3% met the Academy recommendations. CONCLUSIONS: Results suggest that the majority of high SES women did not meet ω-3 recommendations from food alone. Continued prenatal education on the importance of fish intake and on the addition of ω-3 prenatal supplement is essential.


Assuntos
Dieta , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/administração & dosagem , Adulto , Animais , Canadá , Registros de Dieta , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Peixes , Idade Gestacional , Educação em Saúde , Humanos , Estado Nutricional , Gravidez , Terceiro Trimestre da Gravidez , Recomendações Nutricionais , Inquéritos e Questionários
14.
Stroke ; 47(6): 1618-25, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27103017

RESUMO

BACKGROUND AND PURPOSE: We investigated vasoactive properties of leptomeningeal arterioles (LMAs) under normotensive conditions and during hypertension and aging that are known to have poor collateral flow and little salvageable tissue. METHODS: LMAs, identified as distal anastomotic arterioles connecting middle and anterior cerebral arteries, were studied isolated and pressurized from young (18 weeks) or aged (48 weeks) normotensive Wistar Kyoto (WKY18, n=14; WKY48, n=6) rats and spontaneously hypertensive rats (SHR18, n=16; SHR48, n=6). Myogenic tone and vasoactive responses to pressure as well as endothelial function and ion channel activity were measured. RESULTS: LMAs from WKY18 had little myogenic tone at 40 mm Hg (8±3%) that increased in aged WKY48 (30±6%). However, LMAs from both WKY groups dilated to increased pressure and demonstrated little myogenic reactivity, a response that would be conducive to collateral flow. In contrast, LMAs from both SHR18 and SHR48 displayed considerable myogenic tone (56±8% and 43±7%; P<0.01 versus WKY) and constricted to increased pressure. LMAs from both WKY and SHR groups had similar basal endothelial nitric oxide and IK channel activity that opposed tone. However, dilation to sodium nitroprusside, diltiazem and 15 mmol/L KCl was impaired in LMAs from SHR18. CONCLUSIONS: This study shows for the first time that LMAs from young and aged SHR are vasoconstricted and have impaired vasodilatory responses that may contribute to greater perfusion deficit and little penumbral tissue. These results also suggest that therapeutic opening of pial collaterals is possible during middle cerebral artery occlusion to create penumbral tissue and prevent infarct expansion.


Assuntos
Envelhecimento/fisiologia , Vasos Sanguíneos/fisiopatologia , Circulação Cerebrovascular/fisiologia , Circulação Colateral/fisiologia , Hipertensão/fisiopatologia , Pia-Máter/irrigação sanguínea , Vasodilatação/fisiologia , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Acidente Vascular Cerebral/terapia
15.
Transl Stroke Res ; 7(3): 228-38, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27125535

RESUMO

Stroke is a major health issue in women. Our previous studies in male rats showed decreased myogenic tone in middle cerebral arteries (MCAs) after ischemia and reperfusion (I/R), while tone in parenchymal arterioles (PAs) was increased. This vascular response may aggravate stroke damage in males by limiting reperfusion; however, the effect in females is not known. The current study investigated the effect of I/R and tissue plasminogen activator (tPA) on myogenic tone and reactivity of MCAs and PAs in female rats. Nitrosative stress by peroxynitrite and recruitment of inflammatory neutrophils to the microvasculature were also studied. Female rats were subjected to 2-h MCA filament occlusion (n = 16) or sham surgery (n = 17) and given tPA (1 mg/kg, i.v) or vehicle followed by 30-min reperfusion. Myogenic tone and reactivity were measured in isolated and pressurized MCAs and PAs from the same animals. Cerebrovascular F-actin, 3-nitrotyrosine (3-NT, peroxynitrite marker), and intravascular neutrophils were quantified. Myogenic tone and constriction to the nitric oxide synthase inhibitor Nω-nitro-L-arginine were decreased in MCAs but unchanged in PAs after I/R with no effect of tPA. F-actin and 3-NT expression were unaffected by I/R or tPA. Our study showed that MCAs from females, similar to what has been seen in males, are dilated after I/R and have decreased myogenic tone while tone in PAs was unchanged. Increased small vessel resistance may contribute to decreased reperfusion and worse outcome after stroke.


Assuntos
Circulação Cerebrovascular/efeitos dos fármacos , Fibrinolíticos/uso terapêutico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Reperfusão , Ativador de Plasminogênio Tecidual/uso terapêutico , Tirosina/análogos & derivados , Actinas/metabolismo , Amidas/uso terapêutico , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/uso terapêutico , Feminino , Artéria Cerebral Média/efeitos dos fármacos , Artéria Cerebral Média/metabolismo , Músculo Liso/efeitos dos fármacos , Músculo Liso/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/patologia , Ovariectomia , Piridinas/uso terapêutico , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Tirosina/metabolismo
17.
J Cell Physiol ; 230(10): 2522-32, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25802202

RESUMO

Runx1 is a transcription factor essential for definitive hematopoiesis, and genetic abnormalities in Runx1 cause leukemia. Runx1 is functionally promiscuous and acts as either an oncogene or tumor suppressor gene in certain epithelial cancers. Recent evidence suggests that Runx1 is an important factor in breast cancer, however, its role remains ambiguous. Here, we addressed whether Runx1 has a specific pathological role during breast cancer progression and show that Runx1 has an oncogenic function. We observed elevated Runx1 expression in a subset of human breast cancers. Furthermore, throughout the course of disease progression in a classical mouse model of breast cancer (i.e., the MMTV-PyMT transgenic model), Runx1 expression increases in the primary site (mammary gland) and is further upregulated in tumors and distal lung metastatic lesions. Ex vivo studies using tumor epithelial cells derived from these mice express significantly higher levels of Runx1 than normal mammary epithelial cells. The tumor cells exhibit increased rates of migration and invasion, indicative of an aggressive cancer phenotype. Inhibition of Runx1 expression using RNA interference significantly abrogates these cancer-relevant phenotypic characteristics. Importantly, our data establish that Runx1 contributes to murine mammary tumor development and malignancy and potentially represents a key disease-promoting and prognostic factor in human breast cancer progression and metastasis.


Assuntos
Neoplasias da Mama/metabolismo , Movimento Celular/fisiologia , Proliferação de Células/genética , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Neoplasias Mamárias Experimentais/patologia , Neoplasias Epiteliais e Glandulares/patologia , Animais , Neoplasias da Mama/genética , Feminino , Neoplasias Mamárias Experimentais/metabolismo , Vírus do Tumor Mamário do Camundongo/genética , Camundongos , Camundongos Transgênicos , Invasividade Neoplásica
18.
Am J Physiol Heart Circ Physiol ; 307(6): H933-8, 2014 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-25015959

RESUMO

We have previously reported that Zn(2+) infused into the coronary arteries of isolated rat hearts leads to the potent dephosphorylation of phospholamban (PLB) as well as a noticeable but less potent dephosphorylation of the ryanodine receptor 2. We hypothesized in the present study that a Zn(2+)-activated phosphatase is located in the vicinity of the sarcoplasmic reticulum (SR) where PLB and ryanodine receptor 2 reside. We report here the novel finding of tissue-nonspecific alkaline phosphatase (TNAP), a zinc-dependent enzyme, localized to the SR in the cardiac sarcomere of mouse myocardium. TNAP activity was enhanced by injection of Zn acetate into a tail vein before harvesting the heart and imaged using electron microscopy of electron dense deposits indicative of the hydrolysis of exogenous ß-glycerophosphate. TNAP activity was observed localized to the ends of the Z-line corresponding to SR and was qualitatively more visible in myocardium of males compared with females. Correspondingly, PLB phosphorylation status was potently reduced in myocardium of males injected with Zn acetate, whereas there was no apparent effect of Zn acetate injection on PLB phosphorylation in females. Surprisingly, Western blot analysis of TNAP content suggested a significantly lower TNAP content in males compared with females. These data suggest that TNAP plays a role in governing the phosphorylation status of calcium handling proteins in the SR. Furthermore, the content and activity of TNAP are differentially regulated between the sexes and thus may account for some sex differences in cardiopathologies associated with calcium handling.


Assuntos
Fosfatase Alcalina/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Sarcômeros/efeitos dos fármacos , Acetato de Zinco/farmacologia , Animais , Cálcio/metabolismo , Feminino , Injeções Intravenosas , Masculino , Camundongos , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/ultraestrutura , Fosforilação , Sarcômeros/enzimologia , Sarcômeros/ultraestrutura , Fatores Sexuais , Acetato de Zinco/administração & dosagem
19.
J Strength Cond Res ; 28(11): 3049-55, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24796979

RESUMO

The objective of the study was to examine the effect of suspension training on muscle activation during performance of variations of the plank exercise. Twenty-one participants took part. All individuals completed 2 repetitions each of 4 different plank exercises that consisted of a floor based plank, or planks with arms suspended, feet suspended, or feet and arms suspended using a TRX Suspension System. During plank performance, muscle activation was recorded from rectus abdominis, external oblique, rectus femoris, and serratus anterior (SA) muscles using electromyography. All planks were performed for a total of 3 seconds. Resulting muscle activation data were amplitude normalized, and root mean square activation was then determined over the full 3 second duration of the exercise. A significant main effect of plank type was found for all muscles. Post hoc analysis and effect size examination indicated that abdominal muscle activation was higher in all suspended conditions compared to the floor based plank. The highest level of abdominal muscle activation occurred in the arms suspended and arms/feet suspended conditions, which did not differ from one another. Rectus femoris activation was greatest during the arms suspended condition, whereas SA activity peaked during normal and feet suspended planks. These results indicate that suspension training as performed in this study seems to be an effective means of increasing muscle activation during the plank exercise. Contrary to expectations, the additional instability created by suspending both the arms and feet did not result in any additional abdominal muscle activation. These findings have implications in prescription and progression of core muscle training programs.


Assuntos
Músculo Quadríceps/fisiologia , Reto do Abdome/fisiologia , Treinamento Resistido/instrumentação , Eletromiografia , Feminino , Humanos , Masculino , Contração Muscular , Postura , Distribuição Aleatória , Treinamento Resistido/métodos , Extremidade Superior , Adulto Jovem
20.
Micron ; 47: 50-8, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23416165

RESUMO

It is well established that the status of the endoplasmic reticulum (ER) and mitochondria, and the interactions between them, is critical to numerous cellular functions including apoptosis. Mitochondrial dynamics is greatly influenced by cell stress, and recent studies implicate ER in mitochondrial fission. Although a number of proteins have been identified to participate in ER-induced mitochondrial fission, the molecular mechanism of the process is little understood. In the current study, we confirm the involvement of ER in mitochondrial fission and hypothesize the involvement of water channels or aquaporins (AQP) in the process. Previous studies demonstrate the presence of AQP both in the ER and mitochondrial membranes. Mitochondrial swelling has been observed following mitochondrial calcium overload, and studies report that chelation of cytosolic calcium induces extensive mitochondrial division at ER contact sites. Based on this information, the involvement of ER in mitochondrial division, possibly via water channels, is hypothesized. Utilizing a multi-faceted imaging approach consisting of atomic force microscopy on aldehyde-fixed and semi-dry cells, transmission electron microscopy, and immunofluorescence microscopy on live cells, the physical interactions between the two organelles are demonstrated. Mitochondrial fission following ER stress was abrogated with exposure of cells to the AQP inhibitor mercuric chloride, suggesting the involvement of AQP(s) especially AQP8 and AQP9 known to be present in the mitochondrial membrane, in mitochondrial fission.


Assuntos
Aquaporinas/metabolismo , Retículo Endoplasmático/fisiologia , Dinâmica Mitocondrial/fisiologia , Pâncreas Exócrino , Animais , Aquaporinas/farmacologia , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático , Humanos , Masculino , Camundongos , Microscopia Eletrônica , Microscopia de Fluorescência , Dinâmica Mitocondrial/efeitos dos fármacos , Membranas Mitocondriais/metabolismo , Pâncreas Exócrino/citologia , Pâncreas Exócrino/ultraestrutura , Pancreatite/induzido quimicamente , Ratos , Ratos Wistar
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