Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 22
Filtrar
1.
J Emerg Med ; 66(6): e701-e703, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38762374

RESUMO

BACKGROUND: Hidradenitis suppurativa (HS) is a painful, chronic inflammatory skin condition. Patients experience exacerbations, leading them to present to the emergency department (ED) for incision and drainage. Direct injection of local anesthetic into these lesions is extremely painful and seldom provides adequate anesthesia. A modified method of the PECS II block can provide anesthesia to the skin of the axilla, making management of HS much less painful for the patient. We performed a bilateral modified PECS II block on a patient requiring incision and drainage of HS lesions in both axillae. She subsequently required no local anesthetic for the procedure. DISCUSSION: The second injection of the traditional PECS II block involves the deposition of anesthetic in the fascial plane between the pectoralis minor muscle and the serratus anterior muscles. This injection targets the lateral branch of the intercostal nerves, which provide sensory innervation to the axilla. CONCLUSIONS: A modified technique of the PECS II block, in which only the second injection is performed, is a potentially effective method for anesthetizing the axilla of patients with HS prior to incision and drainage.


Assuntos
Anestésicos Locais , Axila , Hidradenite Supurativa , Bloqueio Nervoso , Humanos , Hidradenite Supurativa/complicações , Hidradenite Supurativa/cirurgia , Bloqueio Nervoso/métodos , Feminino , Anestésicos Locais/administração & dosagem , Anestésicos Locais/uso terapêutico , Adulto , Serviço Hospitalar de Emergência , Drenagem/métodos
2.
3D Print Addit Manuf ; 10(5): 869-886, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37886415

RESUMO

A prominent obstacle in scaling up tissue engineering technologies for human applications is engineering an adequate supply of oxygen and nutrients throughout artificial tissues. Sugar glass has emerged as a promising 3D-printable, sacrificial material that can be used to embed perfusable networks within cell-laden matrices to improve mass transfer. To characterize and optimize a previously published sugar ink, we investigated the effects of sucrose, glucose, and dextran concentration on the glass transition temperature (Tg), printability, and stability of 3D-printed sugar glass constructs. We identified a sucrose ink formulation with a significantly higher Tg (40.0 ± 0.9°C) than the original formulation (sucrose-glucose blend, Tg = 26.2 ± 0.4°C), which demonstrated a pronounced improvement in printability, resistance to bending, and final print stability, all without changing dissolution kinetics and decomposition temperature. This formulation allowed printing of 10-cm-long horizontal cantilever filaments, which can enable the printing of complex vascular segments along the x-, y-, and z-axes without the need for supporting structures. Vascular templates with a single inlet and outlet branching into nine channels were 3D printed using the improved formulation and subsequently used to generate perfusable alginate constructs. The printed lattice showed high fidelity with respect to the input geometry, although with some channel deformation after alginate casting and gelation-likely due to alginate swelling. Compared with avascular controls, no significant acute cytotoxicity was noted when casting pancreatic beta cell-laden alginate constructs around improved ink filaments, whereas a significant decrease in cell viability was observed with the original ink. The improved formulation lends more flexibility to sugar glass 3D printing by facilitating the fabrication of larger, more complex, and more stable sacrificial networks. Rigorous characterization and optimization methods for improving sacrificial inks may facilitate the fabrication of functional cellular constructs for tissue engineering, cellular biology, and other biomedical applications.

3.
PLoS Negl Trop Dis ; 17(2): e0011075, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36730440

RESUMO

Aedes aegypti abundance in residential estates is hypothesized to contribute to localised outbreaks of dengue in Singapore. Knowing the factors in the urban environment underlying high Ae. aegypti abundance could guide intervention efforts to reduce Ae. aegypti breeding and the incidence of dengue. In this study, objective data on Ae. aegypti abundance in public apartment blocks estimated by Singapore's nationally representative Gravitrap surveillance system was obtained from the National Environmental Agency. Low and high abundance status public apartment blocks were classified based on the Gravitrap Aegypti Index, corresponding to the lowest and highest quartiles respectively. An environmental case-control study was conducted, wherein a blinded assessment of urban features hypothesised to form breeding habitats was conducted in 50 randomly sampled public apartment blocks with low and high abundance statuses each. Logistic regression was performed to identify features that correlated with abundance status. A multivariable logistic model was created to determine key urban features found in corridors and void decks which were predictive of the Ae. aegypti abundance status of the public apartment block. At a statistical level of significance of 0.20, the presence of gully traps [Odds Ratio (OR): 1.34, 95% Confidence Interval (CI): 1.10, 1.66], age of the public apartment block [OR: 2.23, 95% CI: 1.48, 3.60], housing price [OR: 0.33, 95% CI: 0.16, 0.61] and corridor cleanliness [OR: 0.67, 95% CI: 0.40, 1.07] were identified as important predictors of abundance status. To reduce Ae. aegypti abundance around public apartment blocks and potential onward dengue transmission, gully traps could be remodelled or replaced by other drainage types. Routine inspections of Ae. aegypti breeding should be targeted at older and low-income neighbourhoods. Campaigns for cleaner corridors should be promoted.


Assuntos
Aedes , Dengue , Animais , Humanos , Singapura/epidemiologia , Estudos de Casos e Controles , Ecossistema
4.
Aggress Behav ; 49(2): 141-153, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36408970

RESUMO

Experiencing a thought about harming or injuring another person is commonly reported by the general population. Aggressive intrusive thoughts (AITs) and aggressive scripts are two constructs commonly used to define the experience of thinking about harming another person. However, they are generally investigated separately and with two significantly different population groups; respectively, individuals with obsessive-compulsive disorder and people with a history of violent behavior. AITs and aggressive scripts are assumed to have very different implications for violence risk assessment, but conceptual overlap and an absence of empirical research renders this assumption premature. Using a battery of self-report measures, this study aimed to investigate the differential predictors of AITs and aggressive script rehearsal in a nonclinical sample. Additionally, using regression analyses, the predictors of self-reported aggressive behavior were explored in a sample of 412 adults (73% females; Mage = 31.96 years, SD = 11.02). Violence-supportive beliefs and frequency of anger rumination predicted the frequency of aggressive script rehearsal, and aggressive script rehearsal, anger rumination, and violence-supportive beliefs predicted a history of aggressive behavior. In contrast, obsessive beliefs were predictive of AITs, and only AITs were related to ego-dystonicity. Both AITs and aggressive script rehearsal were related to the use of thought control strategies. These findings support the contributions that maladaptive beliefs have in the experience of aggressive scripts and AITs. Beliefs about violence, a history of aggressive behavior, and ego-dystonicity appear to differentiate aggressive scripts from AITs.


Assuntos
Transtorno Obsessivo-Compulsivo , Adulto , Feminino , Humanos , Masculino , Cognição , Agressão , Ira , Autorrelato
5.
Emerg Radiol ; 30(1): 19-26, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36279080

RESUMO

PURPOSE: We sought to determine the test characteristics of biliary point-of-care ultrasound (POCUS) and to assess the usefulness of obtaining radiology ultrasound (RUS) or cholescintigraphy (HIDA) after biliary POCUS. METHODS: We conducted a retrospective review of emergency department patients who underwent biliary POCUS between May 4, 2018 and November 28, 2021. To be included, patients had to have at least one of the following confirmatory evaluations (considered in this order): surgery, HIDA, RUS, or abdominal CT scan. When a discrepancy existed between the POCUS and the RUS or HIDA, they were compared to a higher criterion standard (if available). RESULTS: Using 348 patients who had a confirmatory evaluation after biliary POCUS, we found the sensitivity and specificity of biliary POCUS for gallstones to be 97.0% (95% CI 92.6 to 99.2%) and 99.5% (95% CI 97.3 to 100%), respectively. For cholecystitis, the sensitivity and specificity were 83.8% (95% CI 72.9 to 91.6%) and 98.6% (95% CI 96.4 to 99.6%), respectively. RUS and POCUS were concordant in 72 (81.8%) of 88 cases in which the patient had both studies while HIDA and POCUS were concordant in 24 (70.6%) of 34 cases. POCUS was deemed correct in at least 50% of discrepant cases with RUS and at least 30% of discrepant cases with HIDA. CONCLUSION: Biliary POCUS has excellent sensitivity and specificity for cholelithiasis; it has lower sensitivity for cholecystitis, but the specificity remains high. Performing a confirmatory RUS or cholescintigraphy after a positive biliary POCUS adds little value, but additional imaging may be useful when POCUS is negative for cholecystitis.


Assuntos
Colecistite , Sistemas Automatizados de Assistência Junto ao Leito , Humanos , Iminoácidos , Ultrassonografia/métodos , Serviço Hospitalar de Emergência
6.
Ther Adv Infect Dis ; 9: 20499361211069264, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35059196

RESUMO

INTRODUCTION: Several reports have emerged describing the long-term consequences of COVID-19 and its effects on multiple systems. METHODS: As further research is needed, we conducted a longitudinal observational study to report the prevalence and associated risk factors of the long-term health consequences of COVID-19 by symptom clusters in patients discharged from the Temporary COVID-19 Hospital (TCH) in Mexico City. Self-reported clinical symptom data were collected via telephone calls over 90 days post-discharge. Among 4670 patients, we identified 45 symptoms across eight symptom clusters (neurological; mood disorders; systemic; respiratory; musculoskeletal; ear, nose, and throat; dermatological; and gastrointestinal). RESULTS: We observed that the neurological, dermatological, and mood disorder symptom clusters persisted in >30% of patients at 90 days post-discharge. Although most symptoms decreased in frequency between day 30 and 90, alopecia and the dermatological symptom cluster significantly increased (p < 0.00001). Women were more prone than men to develop long-term symptoms, and invasive mechanical ventilation also increased the frequency of symptoms at 30 days post-discharge. CONCLUSION: Overall, we observed that symptoms often persisted regardless of disease severity. We hope these findings will help promote public health strategies that ensure equity in the access to solutions focused on the long-term consequences of COVID-19.

7.
Clin Epidemiol Glob Health ; 12: 100868, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34549098

RESUMO

INTRODUCTION: The outbreak of coronavirus posits deleterious consequences on global healthcare system while affecting human life in every aspect. Despite several measures undertaken to limit the socio-economic effect of coronavirus, various challenges remain pervasive, and one such challenge is mental health, particularly depression and anxiety. Therefore, this study examines the prevalence and determinants of depression and anxiety in Malaysian population during third wave of COVID-19. METHODS: A cross-sectional online survey was carried out via social media platforms and 1544 Malaysians were selected. The level of depression was assessed by Patient Health Questionnaires (PHQ-9) and scored accordingly for categorization. Zung's Self-Rating Anxiety Scale (SAS) was used as a self-assessment survey to quantify the level of anxiety of persons experiencing anxiety-related symptoms. Percentage distribution and logistic regression analysis were used in the data analysis. RESULTS: Results showed that one-fourth (25.1%) of the participants had severe depressive symptoms. Almost one-sixth (18.7%) had mild depressive symptoms and one-third (34.1%) had mild to moderate anxiety symptoms. Age, gender, and friends infected with virus were the three important predictors of depression and anxiety. The odds of having depression (OR = 1.44; C·I. = 1.32-1.62) and anxiety (OR = 1.36; C·I. = 1.27-1.47) were significantly higher among females than in males. CONCLUSION: A significant proportion of the study participants were facing mild to severe depression and anxiety symptoms which is very alarming as the pandemic is still now increasing across the country. Immediate interventions including community counselling programmes, TV and social media campaigns are urgently needed to reduce the psychological stress among the Malaysian population.

8.
CMAJ ; 193(31): E1203-E1212, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34373268

RESUMO

BACKGROUND: The COVID-19 pandemic has exacerbated disparities in poverty and illness for people in vulnerable circumstances in ethnocultural communities. We sought to understand the evolving impacts of COVID-19 on ethnocultural communities to inform intersectoral advocacy and community action. METHODS: The Illuminate Project used participatory action research, with cultural health brokers as peer researchers, from Sept. 21 to Dec. 31, 2020, in Edmonton, Alberta. Twenty-one peer researchers collected narratives from members of ethnocultural communities and self-interpreted them as they entered the narratives into the SenseMaker platform, a mixed-method data collection tool. The entire research team analyzed real-time, aggregate, quantitative and qualitative data to identify emerging thematic domains, then visualized these domains with social network analysis. RESULTS: Brokers serving diverse communities collected 773 narratives. Identified domains illuminate the evolving and entangled impacts of COVID-19 including the following: COVID-19 prevention and management; care of acute, chronic and serious illnesses other than COVID-19; maternal care; mental health and triggers of past trauma; financial insecurity; impact on children and youth and seniors; and legal concerns. We identified that community social capital and cultural brokering are key assets that facilitate access to formal health and social system supports. INTERPRETATION: The Illuminate Project has illustrated the entangled, systemic issues that result in poor health among vulnerable members of ethnocultural communities, and the exacerbating effects of COVID-19, which also increased barriers to mitigation. Cultural brokering and community social capital are key supports for people during the COVID-19 pandemic. These findings can inform policy to reduce harm and support community resiliency.


Assuntos
COVID-19/etnologia , Serviços de Saúde Comunitária/organização & administração , Pandemias , Populações Vulneráveis/etnologia , Alberta/epidemiologia , COVID-19/prevenção & controle , COVID-19/terapia , Informação de Saúde ao Consumidor , Feminino , Estresse Financeiro , Pesquisa sobre Serviços de Saúde , Disparidades em Assistência à Saúde , Humanos , Masculino , Pobreza , SARS-CoV-2 , Capital Social , Análise de Rede Social , Apoio Social
9.
Front Bioeng Biotechnol ; 9: 674125, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34124024

RESUMO

Transplantation of hydrogel-encapsulated pancreatic islets is a promising long-term treatment for type 1 diabetes that restores blood glucose regulation while providing graft immunoprotection. Most human-scale islet encapsulation devices that rely solely on diffusion fail to provide sufficient surface area to meet islet oxygen demands. Perfused macroencapsulation devices use blood flow to mitigate oxygen limitations but increase the complexity of blood-device interactions. Here we describe a human-scale in vitro perfusion system to study hemocompatibility and performance of islet-like cell clusters (ILCs) in alginate hydrogel. A cylindrical perfusion device was designed for multi-day culture without leakage, contamination, or flow occlusion. Rat blood perfusion was assessed for prothrombin time and international normalized ratio and demonstrated no significant change in clotting time. Ex vivo perfusion performed with rats showed patency of the device for over 100 min using Doppler ultrasound imaging. PET-CT imaging of the device successfully visualized metabolically active mouse insulinoma 6 ILCs. ILCs cultured for 7 days under static conditions exhibited abnormal morphology and increased activated caspase-3 staining when compared with the perfused device. These findings reinforce the need for convective transport in macroencapsulation strategies and offer a robust and versatile in vitro system to better inform preclinical design.

10.
J Psychosom Res ; 124: 109756, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31443810

RESUMO

Endometriosis is a common gynecological condition associated with debilitaing pain and poor mental health. This review examines the evidence for psychological and mind-body (PMB) interventions to improve endometriosis pain, psychological distress, sleep and fatigue. Electronic databases searched included PsychINFO, MEDLINE, CINAHL, EMBASE, Cochrane Library, Scopus, and PubMed. Inclusion criteria were women with endometriosis, and interventions that used psychological or mind-body interventions; there were no exclusion criteria regarding study design. Studies were identified and coded using standard criteria, and risk of bias was assessed with established tools relevant to the study design. A total of 12 publications relating to 9 separate studies were identified:- 3 randomized controlled trials, 1 controlled trial, 2 single-arm studies, 1 retrospective cohort study, and 2 case series. Interventions included yoga, mindfulness, relaxation training, cognitive behavioural therapy combined with physical therapy, Chinese medicine combined with psychotherapy, and biofeedback. Results indicate that no studies have yet used gold-standard methodology and, thus, definitive conclusions cannot be offered about PMB efficacy. However, the results of these pilot studies suggest that PMB interventions show promise in alleviating pain, anxiety, depression, stress and fatigue in women with endometriosis, and future well-designed RCTs including active control groups are warranted.


Assuntos
Endometriose/psicologia , Endometriose/terapia , Terapias Mente-Corpo , Feminino , Humanos
11.
Dev Neurobiol ; 77(4): 419-437, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-26999672

RESUMO

Serotonin (5HT) is present in a subpopulation of amacrine cells, which form synapses with retinal ganglion cells (RGCs), but little is known about the physiological role of retinal serotonergic circuitry. We found that the 5HT receptor 2C (5HTR2C) is upregulated in RGCs after birth. Amacrine cells generate 5HT and about half of RGCs respond to 5HTR2C agonism with calcium elevation. We found that there are on average 83 5HT+ amacrine cells randomly distributed across the adult mouse retina, all negative for choline acetyltransferase and 90% positive for tyrosine hydroxylase. We also investigated whether 5HTR2C and 5HTR5A affect RGC neurite growth. We found that both suppress neurite growth, and that RGCs from the 5HTR2C knockout (KO) mice grow longer neurites. Furthermore, 5HTR2C is subject to post-transcriptional editing, and we found that only the edited isoform's suppressive effect on neurite growth could be reversed by a 5HTR2C inverse agonist. Next, we investigated the physiological role of 5HTR2C in the retina, and found that 5HTR2C KO mice showed increased amplitude on pattern electroretinogram. Finally, RGC transcriptional profiling and pathways analysis suggested partial developmental compensation for 5HTR2C absence. Taken together, our findings demonstrate that 5HTR2C regulates neurite growth and RGC activity and is necessary for normal amplitude of RGC response to physiologic stimuli, and raise the hypothesis that these functions are modulated by a subset of 5HT+/ChAT-/TH+ amacrine cells as part of retinal serotonergic circuitry. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 419-437, 2017.


Assuntos
Células Amácrinas/fisiologia , Neuritos/fisiologia , Neurogênese/fisiologia , Receptor 5-HT2C de Serotonina/fisiologia , Células Ganglionares da Retina/fisiologia , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia , Visão Ocular/fisiologia , Animais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurogênese/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptores de Serotonina
12.
Can Oncol Nurs J ; 25(1): 37-48, 2015.
Artigo em Inglês, Francês | MEDLINE | ID: mdl-26642493

RESUMO

The purpose of this investigation was to explore the barriers and facilitators to exercise in individuals with cancer in Ontario. A cross-sectional study using an online survey was used to collect qualitative and quantitative data. A convenience sample was used to recruit individuals with a current or previous diagnosis of any type of cancer. Percentages and themes were obtained from the data. Data were collected from 30 participants of which 63.3% reported infrequent, low intensity physical activity during treatment. Barriers to exercise during treatment included physical symptoms and lack of awareness of exercise programs. Facilitators for exercise were past positive experience with exercise and accessibility. More than 80% of participants did not receive education on the importance of exercise.


Assuntos
Exercício Físico , Neoplasias/fisiopatologia , Neoplasias/terapia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/enfermagem
13.
J Biol Chem ; 290(21): 13417-26, 2015 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-25833944

RESUMO

Set-ß protein plays different roles in neurons, but the diversity of Set-ß neuronal isoforms and their functions have not been characterized. The expression and subcellular localization of Set-ß are altered in Alzheimer disease, cleavage of Set-ß leads to neuronal death after stroke, and the full-length Set-ß regulates retinal ganglion cell (RGC) and hippocampal neuron axon growth and regeneration in a subcellular localization-dependent manner. Here we used various biochemical approaches to investigate Set-ß isoforms and their role in the CNS, using the same type of neurons, RGCs, across studies. We found multiple alternatively spliced isoforms expressed from the Set locus in purified RGCs. Set transcripts containing the Set-ß-specific exon were the most highly expressed isoforms. We also identified a novel, alternatively spliced Set-ß transcript lacking the nuclear localization signal and demonstrated that the full-length (∼39-kDa) Set-ß is localized predominantly in the nucleus, whereas a shorter (∼25-kDa) Set-ß isoform is localized predominantly in the cytoplasm. Finally, we show that an N-terminal Set-ß cleavage product can induce neuronal death.


Assuntos
Processamento Alternativo/genética , Apoptose , Proteínas de Transporte/metabolismo , Neurônios/patologia , Proteínas Nucleares/metabolismo , Proteínas Oncogênicas/metabolismo , Células Ganglionares da Retina/patologia , Animais , Animais Recém-Nascidos , Western Blotting , Proteínas de Transporte/genética , Proliferação de Células , Células Cultivadas , Proteínas de Ligação a DNA , Imunofluorescência , Chaperonas de Histonas , Técnicas Imunoenzimáticas , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Proteínas Nucleares/genética , Proteínas Oncogênicas/genética , Isoformas de Proteínas , RNA Mensageiro/genética , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Células Ganglionares da Retina/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
14.
J Neurosci ; 34(21): 7361-74, 2014 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-24849368

RESUMO

The failure of the CNS neurons to regenerate axons after injury or stroke is a major clinical problem. Transcriptional regulators like Set-ß are well positioned to regulate intrinsic axon regeneration capacity, which declines developmentally in maturing CNS neurons. Set-ß also functions at cellular membranes and its subcellular localization is disrupted in Alzheimer's disease, but many of its biological mechanisms have not been explored in neurons. We found that Set-ß was upregulated postnatally in CNS neurons, and was primarily localized to the nucleus but was also detected in the cytoplasm and adjacent to the plasma membrane. Remarkably, nuclear Set-ß suppressed, whereas Set-ß localized to cytoplasmic membranes promoted neurite growth in rodent retinal ganglion cells and hippocampal neurons. Mimicking serine 9 phosphorylation, as found in Alzheimer's disease brains, delayed nuclear import and furthermore blocked the ability of nuclear Set-ß to suppress neurite growth. We also present data on gene regulation and protein binding partner recruitment by Set-ß in primary neurons, raising the hypothesis that nuclear Set-ß may preferentially regulate gene expression whereas Set-ß at cytoplasmic membranes may regulate unique cofactors, including PP2A, which we show also regulates axon growth in vitro. Finally, increasing recruitment of Set-ß to cellular membranes promoted adult rat optic nerve axon regeneration after injury in vivo. Thus, Set-ß differentially regulates axon growth and regeneration depending on subcellular localization and phosphorylation.


Assuntos
Axônios/metabolismo , Membrana Celular/metabolismo , Regeneração Nervosa/genética , Neurônios/ultraestrutura , Traumatismos do Nervo Óptico/fisiopatologia , Proteínas Pol1 do Complexo de Iniciação de Transcrição/metabolismo , Fatores Etários , Animais , Animais Recém-Nascidos , Células Cultivadas , Modelos Animais de Doenças , Embrião de Mamíferos , Regulação da Expressão Gênica no Desenvolvimento/genética , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Hipocampo/citologia , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Traumatismos do Nervo Óptico/patologia , Proteínas Pol1 do Complexo de Iniciação de Transcrição/genética , Ratos , Ratos Sprague-Dawley , Retina/citologia
15.
Pharmacol Rev ; 64(1): 65-87, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22090472

RESUMO

Striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific phosphatase that modulates key signaling molecules involved in synaptic plasticity and neuronal function. Targets include extracellular-regulated kinase 1 and 2 (ERK1/2), stress-activated protein kinase p38 (p38), the Src family tyrosine kinase Fyn, N-methyl-D-aspartate receptors (NMDARs), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). STEP-mediated dephosphorylation of ERK1/2, p38, and Fyn leads to inactivation of these enzymes, whereas STEP-mediated dephosphorylation of surface NMDARs and AMPARs promotes their endocytosis. Accordingly, the current model of STEP function posits that it opposes long-term potentiation and promotes long-term depression. Phosphorylation, cleavage, dimerization, ubiquitination, and local translation all converge to maintain an appropriate balance of STEP in the central nervous system. Accumulating evidence over the past decade indicates that STEP dysregulation contributes to the pathophysiology of several neuropsychiatric disorders, including Alzheimer's disease, schizophrenia, fragile X syndrome, epileptogenesis, alcohol-induced memory loss, Huntington's disease, drug abuse, stroke/ischemia, and inflammatory pain. This comprehensive review discusses STEP expression and regulation and highlights how disrupted STEP function contributes to the pathophysiology of diverse neuropsychiatric disorders.


Assuntos
Transtornos Mentais , Doenças do Sistema Nervoso , Proteínas Tirosina Fosfatases não Receptoras , Encéfalo/metabolismo , Dimerização , Humanos , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/etiologia , Transtornos Mentais/metabolismo , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/metabolismo , Fosforilação , Conformação Proteica , Proteínas Tirosina Fosfatases não Receptoras/genética , Proteínas Tirosina Fosfatases não Receptoras/metabolismo , Proteínas Tirosina Fosfatases não Receptoras/fisiologia , Especificidade por Substrato
16.
Proc Natl Acad Sci U S A ; 107(44): 19014-9, 2010 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-20956308

RESUMO

Alzheimer's disease (AD) is a progressive and incurable neurodegenerative disorder. Early in the pathophysiology of AD, synaptic function is disrupted by soluble Aß oligomers, possibly through Aß-mediated internalization of NMDA receptors. Striatal-enriched phosphatase (STEP) is a tyrosine phosphatase that regulates the internalization of NMDA receptors. Recent work shows that STEP is elevated in the prefrontal cortex of human AD patients and in animal models of AD. Here, we use genetic manipulations to reduce STEP activity in a triple transgenic AD mouse model and show that a decrease in STEP levels reverses cognitive and cellular deficits observed in these mice. Our results suggest that STEP inhibitors may prove therapeutic for this devastating disorder.


Assuntos
Doença de Alzheimer/enzimologia , Córtex Cerebral/enzimologia , Proteínas Tirosina Fosfatases não Receptoras/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Córtex Cerebral/patologia , Modelos Animais de Doenças , Inibidores Enzimáticos/uso terapêutico , Humanos , Camundongos , Camundongos Transgênicos , Proteínas Tirosina Fosfatases não Receptoras/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo
17.
Biochim Biophys Acta ; 1800(10): 1045-55, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19913600

RESUMO

Traditional approaches to the study of hormones and cognition have been primarily observational or correlational in nature. Because this work does not permit causal relationships to be identified, very little is known about the specific molecules and cellular events through which hormones affect cognitive function. In this review, we propose a new approach to study hormones and memory, where the systematic blocking of cellular events can reveal which such events are necessary for hormones to influence memory consolidation. The discussion will focus on the modulation of the hippocampus and hippocampal memory by estrogens, given the extensive literature on this subject, and will illustrate how the application of this approach is beginning to reveal important new information about the molecular mechanisms through which estrogens modulate memory consolidation. The clinical relevance of this work will also be discussed.


Assuntos
Cognição/fisiologia , Estrogênios/metabolismo , Hipocampo/metabolismo , Memória/fisiologia , Animais , Humanos
18.
J Neurosci ; 28(35): 8660-7, 2008 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-18753366

RESUMO

The extracellular signal-regulated kinase (ERK) pathway is critical for various forms of learning and memory, and is activated by the potent estrogen 17beta-estradiol (E(2)). Here, we asked whether E(2) modulates memory via ERK activation and putative membrane-bound estrogen receptors (ERs). Using ovariectomized mice, we first demonstrate that intraperitoneal injection of 0.2 mg/kg E(2) significantly increases dorsal hippocampal levels of phosphorylated ERK protein 1 h after injection. Second, we show that E(2) administered intraperitoneally (0.2 mg/kg) or via intrahippocampal infusion (5.0 microg/side) immediately after training in an object recognition task significantly enhances memory retention, and that the beneficial effect of intraperitoneal E(2) is blocked by dorsal hippocampal inhibition of ERK activation. Third, using bovine serum albumin-conjugated 17beta-estradiol (BSA-E(2)), we demonstrate that E(2) binding at membrane-bound ERs can increase dorsal hippocampal ERK activation and enhance object memory consolidation in an ERK-dependent manner. Fourth, we show that this effect is independent of nuclear ERs, but is dependent on the dorsal hippocampus. By demonstrating that E(2) enhances memory consolidation via dorsal hippocampal ERK activation, this study is the first to identify a specific molecular pathway by which E(2) modulates memory and to demonstrate a novel role for membrane-bound ERs in mediating E(2)-induced improvements in hippocampal memory consolidation.


Assuntos
Estradiol/farmacologia , Estrogênios/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hipocampo/efeitos dos fármacos , Receptores de Estrogênio/fisiologia , Reconhecimento Psicológico/efeitos dos fármacos , Aminoacetonitrila/análogos & derivados , Aminoacetonitrila/farmacologia , Análise de Variância , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento de Escolha/efeitos dos fármacos , Vias de Administração de Medicamentos , Inibidores Enzimáticos/farmacologia , Comportamento Exploratório/efeitos dos fármacos , Feminino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Muscimol/farmacologia , Ovariectomia/métodos , Fatores de Tempo
19.
Neurobiol Learn Mem ; 83(3): 206-16, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15820856

RESUMO

Environmental enrichment paradigms that incorporate cognitive stimulation, exercise, and motor learning benefit memory and synaptic plasticity across the rodent lifespan. However, the contribution each individual element of the enriched environment makes to enhancing memory and synaptic plasticity has yet to be delineated. Therefore, the current study tested the effects of three of these elements on memory and synaptic protein levels. Young female C57BL/6 mice were given 3h of daily exposure to either rodent toys (cognitive stimulation) or running wheels (exercise), or daily acrobatic training for 6 weeks prior to and throughout behavioral testing. Controls were group housed, but did not receive enrichment. Spatial working and reference memory were tested in a water-escape motivated radial arm maze. Levels of the presynaptic protein synaptophysin were then measured in frontoparietal cortex, hippocampus, striatum, and cerebellum. Exercise, but not cognitive stimulation or acrobat training, improved spatial working memory relative to controls, despite the fact that both exercise and cognitive stimulation increased synaptophysin levels in the neocortex and hippocampus. These data suggest that exercise alone is sufficient to improve working memory, and that enrichment-induced increases in synaptophysin levels may not be sufficient to improve working memory in young females. Spatial reference memory was unaffected by enrichment. Acrobat training had no effect on memory or synaptophysin levels, suggesting a minimal contribution of motor learning to the mnemonic and neuronal benefits of enrichment. These results provide the first evidence that different elements of the enriched environment have markedly distinct effects on spatial memory and synaptic alterations.


Assuntos
Encéfalo/metabolismo , Aprendizagem em Labirinto/fisiologia , Condicionamento Físico Animal/fisiologia , Meio Social , Percepção Espacial/fisiologia , Sinaptofisina/metabolismo , Animais , Cerebelo/metabolismo , Corpo Estriado/metabolismo , Reação de Fuga/fisiologia , Feminino , Hipocampo/metabolismo , Memória/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Neocórtex/metabolismo , Comportamento Espacial/fisiologia
20.
Behav Neurosci ; 118(6): 1340-51, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15598143

RESUMO

This study tested whether chronic oral estrogen could improve memory and alter neural plasticity in the hippocampus and neocortex of middle-aged female mice. Ovariectomized C57BL/6 mice were administered 1,000, 1,500, or 2,500 nM 17beta-estradiol in drinking water for 5 weeks prior to and during spatial and object memory testing. Synaptophysin, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) levels were then measured in hippocampus and neocortex. The medium dose impaired spatial reference memory in the radial-arm maze, whereas all doses improved object recognition. The high dose increased hippocampal synaptophysin and NGF levels, whereas the medium dose decreased these neocortical levels. The high dose decreased neocortical BDNF levels. These data suggest that chronic oral estrogen selectively affects memory and neural function in middle-aged female mice.


Assuntos
Química Encefálica/efeitos dos fármacos , Estradiol/farmacologia , Memória/efeitos dos fármacos , Administração Oral , Animais , Comportamento Animal , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática/métodos , Comportamento Exploratório/efeitos dos fármacos , Feminino , Lobo Frontal/efeitos dos fármacos , Lateralidade Funcional , Hipocampo/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Crescimento Neural/metabolismo , Testes Neuropsicológicos , Tamanho do Órgão/efeitos dos fármacos , Ovariectomia/métodos , Reconhecimento Psicológico/efeitos dos fármacos , Sinaptofisina/metabolismo , Útero/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA