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1.
Osteoporos Int ; 32(3): 549-558, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32888047

RESUMO

We investigated the effect of 12 months of functional electrical stimulation-assisted rowing with and without zoledronic acid (ZA) on computationally estimated bone strength and stiffness in individuals with spinal cord injury. We found that rowing with ZA, but not rowing alone, improved stiffness at the distal femur, but not the proximal tibia. INTRODUCTION: People with spinal cord injury (SCI) have high fracture risk at the knee after the injury. Therapies that prevent bone loss or stimulate an anabolic response in bone have been proposed to reduce fractures. Zoledronic acid (ZA) is a potent bisphosphonate that inhibits osteoclastic resorption. Functional electrical stimulation (FES)-assisted rowing is a potentially osteogenic exercise involving mechanical stimulation to the lower extremities. Here, we investigated the effect of FES-assisted rowing with and without ZA on bone strength and stiffness in individuals with SCI. METHODS: Twenty individuals from a cohort of adults with SCI who participated in a clinical trial were included in the study. CT scans of their knees before and after the intervention were converted to finite element models. Bone failure strength (Tult) and stiffness were calculated at the proximal tibia and distal femur. RESULTS: Tult at the distal femur increased 4.6% among people who received rowing + ZA and decreased 13.9% among those with rowing only (p < 0.05 for group). Torsional and compressive stiffness at the femur metaphysis increased in people with rowing + ZA (+ 3 to +4%) and decreased in people with rowing only (- 7 to -8%; p < 0.05). Tult in the proximal tibia decreased in everyone, but the loss was attenuated in the rowing + ZA group. People with initially stronger bone tended to lose more strength. CONCLUSION: Overall, we observed increases in bone strength at the distal femur but not the proximal tibia, with FES-assisted rowing combined with ZA treatment. Rowing alone did not significantly prevent bone loss at either site, which might be attributed to insufficient mechanical loading.


Assuntos
Traumatismos da Medula Espinal , Esportes Aquáticos , Adulto , Densidade Óssea , Estimulação Elétrica , Fêmur , Humanos , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/terapia , Ácido Zoledrônico/uso terapêutico
2.
Chron Respir Dis ; 15(1): 41-47, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28786297

RESUMO

Several different applications of telehealth technologies have been used in the care of respiratory patients, including telemonitoring, teleconsultations, tele-education, and telehealth-pulmonary rehabilitation (PR). Telehealth technology provides an opportunity to assist in the management of chronic respiratory diseases and improve access to PR programs. While there is inconclusive evidence as to the effectiveness of telemonitoring to reduce healthcare utilization and detection of exacerbations, teleconsultations have been shown to be an effective means to assess patients' disease prior to the initiation of PR, and telehealth PR has been shown to be as effective as institution-based PR at improving functional exercise capacity and health-related quality of life. To improve PR access across Canada and ensure a high standard of program quality, a team of clinicians and researchers has developed and begun to implement a national standardized PR program that can be delivered across different settings of practice, including remote satellite sites via telehealth PR. The program has adapted the "Living Well with COPD" self-management program and includes standardized reference guides and resources for patients and practitioners. A progressive and iterative process will evaluate the success of program implementation and outcomes. This initiative will address nationwide accessibility challenges and provide PR content as well as evaluations that are in accordance with clinical standards and established self-management practices.


Assuntos
Doença Pulmonar Obstrutiva Crônica/reabilitação , Telerreabilitação/métodos , Canadá , Acessibilidade aos Serviços de Saúde , Humanos , Telemedicina/métodos
3.
Environ Geochem Health ; 40(1): 1-57, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27921191

RESUMO

The public health impact of hydraulic fracturing remains a high profile and controversial issue. While there has been a recent surge of published papers, it remains an under-researched area despite being possibly the most substantive change in energy production since the advent of the fossil fuel economy. We review the evidence of effects in five public health domains with a particular focus on the UK: exposure, health, socio-economic, climate change and seismicity. While the latter would seem not to be of significance for the UK, we conclude that serious gaps in our understanding of the other potential impacts persist together with some concerning signals in the literature and legitimate uncertainties derived from first principles. There is a fundamental requirement for high-quality epidemiological research incorporating real exposure measures, improved understanding of methane leakage throughout the process, and a rigorous analysis of the UK social and economic impacts. In the absence of such intelligence, we consider it prudent to incentivise further research and delay any proposed developments in the UK. Recognising the political realities of the planning and permitting process, we make a series of recommendations to protect public health in the event of hydraulic fracturing being approved in the UK.


Assuntos
Fraturamento Hidráulico , Gás Natural , Saúde Pública , Animais , Mudança Climática , Terremotos , Exposição Ambiental , Humanos , Fatores Socioeconômicos , Reino Unido
4.
Spinal Cord ; 55(12): 1088-1095, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28762383

RESUMO

STUDY DESIGN: Cross-sectional study. OBJECTIVES: Determine clinical factors associated with plasma C-reactive protein (CRP) in persons with chronic spinal cord injury (SCI). SETTING: Veterans Affairs Medical Center in Boston, MA, USA. METHODS: Participants provided a blood sample, completed a respiratory health questionnaire and underwent dual X-ray absorptiometry (DXA) to assess total and regional body fat. Linear regression models were used to assess cross-sectional associations with plasma CRP. RESULTS: In multivariable models, factors associated with a higher CRP included a greater BMI, urinary catheter use, a respiratory illness in the past week and non-white race. Mean CRP also increased with decreasing mobility (motorized wheelchair >hand-propelled wheelchair >walk with an assistive device >walk independently). Results were similar when adjusting for percentage android, gynoid, trunk or total fat mass in place of BMI. Level and completeness of SCI was not associated with CRP in multivariable models. CONCLUSIONS: Clinical characteristics common in chronic SCI are associated with plasma CRP. These factors are more important than the level and completeness of SCI and some are potentially modifiable.


Assuntos
Proteína C-Reativa/análise , Traumatismos da Medula Espinal/sangue , Absorciometria de Fóton , Tecido Adiposo/diagnóstico por imagem , Biomarcadores/sangue , Composição Corporal , Doença Crônica , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/diagnóstico por imagem , Traumatismos da Medula Espinal/reabilitação , Inquéritos e Questionários
5.
Am J Transplant ; 16(4): 1298-305, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26601796

RESUMO

Renal transplant biopsies to diagnose transplant pathology are routinely performed using ultrasound guidance. Few large studies have assessed the rate and risk factors of major biopsy complications. This study is a single-center 5-year retrospective cohort analysis of 2514 biopsies. Major complications occurred in 47 of 2514 patients (1.9%) and included hospitalization, transfusion of blood products, operative exploration and interventional radiology procedures. The complication rate among "cause" biopsies was significantly higher than in "protocol" biopsies (2.7% vs. 0.33%, p < 0.001). Complications presented on postbiopsy days 0-14, with the majority diagnosed on the same day as the biopsy and manifested by hematocrit drop, although the presence of such delayed presentation of complications occurring >24 h after the biopsy on days 2-14 is previously unreported. Specific patient characteristics associated with increased risk of a complication were increased age and blood urea nitrogen, decreased platelet count, history of prior renal transplant, deceased donor transplant type and use of anticoagulant medications but not aspirin.


Assuntos
Transfusão de Sangue , Hospitalização/estatística & dados numéricos , Biópsia Guiada por Imagem/efeitos adversos , Falência Renal Crônica/cirurgia , Transplante de Rim , Rim/patologia , Ultrassonografia de Intervenção/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
6.
Geophys Res Lett ; 42(13): 5125-5131, 2015 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-27656008

RESUMO

As Rosetta was orbiting comet 67P/Churyumov-Gerasimenko, the Ion and Electron Sensor detected negative particles with angular distributions like those of the concurrently measured solar wind protons but with fluxes of only about 10% of the proton fluxes and energies of about 90% of the proton energies. Using well-known cross sections and energy-loss data, it is determined that the fluxes and energies of the negative particles are consistent with the production of H- ions in the solar wind by double charge exchange with molecules in the coma.

7.
Br J Cancer ; 110(9): 2269-76, 2014 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-24667644

RESUMO

BACKGROUND: Challenges in developing drugs for pancreatic ductal adenocarcinoma (PDAC) include obtaining metastatic cancer tissue for research and validating biomarkers predicative for personalised therapeutic decisions. We have recently developed a novel therapeutic model for PDAC to address these challenges based on the isolation of viable PDAC cells derived from ascites fluid. METHODS: Ascites fluid was obtained from PDAC patients undergoing palliative paracentesis. Ascites-derived PDAC primary cells were isolated, cultured and characterised in ovo and in vitro. RESULTS: We successfully established ascites-derived primary cell cultures within 2-7 days from 92% (93 out of 101) of the ascites fluid samples obtained (from 36 different patients). Homogeneous epithelial PDAC-enriched cell cultures were identified and characterised. We observed a wide range in doubling times and migration properties among the different patient-derived cell cultures. The diverse nature of each individual patient's cell cultures was further demonstrated by differences in therapeutic susceptibility and resistance. The tumorigenicity and invasiveness of the cells were demonstrated in vivo using chicken chorioallantoic membrane grafts. CONCLUSIONS: We have developed a unique ascites-derived PDAC primary cell culture model. This model has the potential to study signalling pathways in PDAC progression and to evaluate targeted therapies for the individual patient expeditiously, thereby supporting personalised treatment decisions.


Assuntos
Ascite/patologia , Líquido Ascítico/patologia , Carcinoma Ductal Pancreático/metabolismo , Neoplasias Pancreáticas/patologia , Medicina de Precisão , Cultura Primária de Células/métodos , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Separação Celular , Embrião de Galinha , Membrana Corioalantoide , Transição Epitelial-Mesenquimal , Humanos , Terapia de Alvo Molecular , Neoplasias Pancreáticas
8.
Respir Med ; 225: 107588, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38460709

RESUMO

BACKGROUND: Pulmonary rehabilitation (PR) plays an important role in the management of symptomatic patients with chronic respiratory diseases (CRD). While studies have investigated the feasibility and efficacy of virtual PR (VPR), it is important to understand the experiences of patients and healthcare providers (HCPs) during the rapid digital health transformation that occurred in the COVID-19 pandemic. OBJECTIVES: To explore the experiences and perspectives of patients and HCPs who participated in VPR during the pandemic. METHODS: Semi-structured interviews were conducted with CRD patients and HCPs. This study used a qualitative descriptive approach and a team-based inductive thematic analysis. RESULTS: Participants included 11 HCPs (7 female; 29-55 years) and 19 CRD patients (11 male; 62-83 years; 15 COPD, 4 COPD/ILD). Three major themes and 10 subthemes were identified: i) the pandemic response: a 'trial by fire' (navigating uncertainty, emotional impact of change, shifting practice amid complexity); ii) beyond the emergency: navigating a 'new normal' (eligibility and assessment for VPR, virtual exercise, virtual education and resources, clinical supervision and patient safety); and iii) care beyond boundaries: the implications of using technology for PR (benefits and limitations of technology, psychosocial implications, VPR in the future). CONCLUSION: The pivot to VPR was acknowledged as positive by both patients and HCPs although both groups were mindful of the implementation challenges. These findings provide insight into the experience of HCPs and patients in introducing VPR in response to the pandemic and will inform future implementation of VPR for individuals with CRD.


Assuntos
COVID-19 , Doença Pulmonar Obstrutiva Crônica , Telerreabilitação , Humanos , Feminino , Masculino , Pandemias , COVID-19/epidemiologia , Pessoal de Saúde , Pesquisa Qualitativa
9.
Int J Med Inform ; 177: 105114, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37329765

RESUMO

BACKGROUND: Chronic diseases are a leading cause of death and disease burden globally. Digital interventions could be an approach to improve patients' ability to find, evaluate, and use health information. OBJECTIVES: The main objective was to conduct a systematic review to determine the effect of digital interventions on digital health literacy for patients living with chronic disease. Secondary objectives were to provide an overviewof the design and delivery characteristics of interventions that impact digital health literacy in people with chronic disease. METHODS: Randomized controlled trials examining digital health literacy (and related components) for individuals with cardiovascular disease, chronic lung disease, osteoarthritis, diabetes, chronic kidney disease, and HIV were identified. This review was conducted following the PRIMSA guidelines. Certainty was assessed using GRADE and the Cochrane risk of bias tool. Meta-analyses were conducted using Review Manager 5.1. The protocol was registered on PROSPERO (CRD42022375967). RESULTS: 9386 articles were identified and 17 articles representing 16 unique trials were included. Studies evaluated 5138 individuals with one or more chronic conditions (50% women, ages 42 ± 7-71 ± 12 years). The most targeted conditions were cancer, diabetes, cardiovascular disease, and HIV. Interventions included: skills training, websites, electronic personal health records, remote patient monitoring, and education. The effects of the interventions were related to: (i) digital health literacy, (ii) health literacy, (iii) health information skills, (iv) technology skills and access, and (v) self-management and participation in care. A meta-analysis of three studies identified the effect of digital interventions was better than usual care for eHealth literacy (1.22 [CI 0.55, 1.89], p < 0.001). CONCLUSIONS: The evidence of the effects of digital interventions on related health literacy is limited. Existing studies reflect the heterogeneity in study design, population, and outcome measures. There is a need for further studies on the effects of digital interventions on related health literacy for individuals with chronic conditions.


Assuntos
Doenças Cardiovasculares , Infecções por HIV , Letramento em Saúde , Insuficiência Renal Crônica , Humanos , Feminino , Masculino , Doenças Cardiovasculares/terapia , Doença Crônica
10.
Sleep Med ; 101: 221-227, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36435158

RESUMO

OBJECTIVE: Early screening and diagnosis of nocturnal hypoventilation can slow progression to diurnal hypercapnia and mortality in children with neuromuscular disease (NMD). However, gold standard, laboratory-based polysomnography (PSG) testing is a limited resource. Therefore, we evaluated the diagnostic accuracy of ambulatory transcutaneous carbon dioxide (tcCO2) monitoring used in the home compared to PSG in children with NMD. METHODS: Prospective, cross-sectional study in children 0-18 years old with a confirmed diagnosis of NMD and a clinically indicated need for PSG. Ambulatory tcCO2 was assessed by a respiratory therapist in participant's homes. Demographics, and PSG (including tcCO2). RESULTS: We enrolled 39 children with NMD; 3 had unusable ambulatory tcCO2 data because of failure of drift correction on the machine (n = 2) or an air bubble (n = 1). The remaining 36 patients aged 11 months to 16 years (median (IQR) 12.5 years (6.0-15.8)) had ambulatory tcCO2 and outpatient level 1 PSG data. Ambulatory tcCO2 monitoring had a sensitivity of 20.0% (95% confidence interval [CI] 0.5-71.6%) and a specificity of 93.5% (95% CI 78.6-99.2%). Almost all children and/or parents (34/36, 94%) preferred ambulatory monitoring over in-hospital PSG. CONCLUSIONS: Ambulatory transcutaneous carbon dioxide monitoring was not sufficiently accurate as a clinical tool for the diagnosis of nocturnal hypoventilation our cohort of children with neuromuscular disease despite being preferred over PSG by both children and parents.


Assuntos
Dióxido de Carbono , Doenças Neuromusculares , Humanos , Criança , Recém-Nascido , Lactente , Pré-Escolar , Adolescente , Hipoventilação/diagnóstico , Estudos Transversais , Estudos Prospectivos , Polissonografia , Doenças Neuromusculares/diagnóstico , Monitorização Ambulatorial
11.
Mol Psychiatry ; 16(11): 1147-54, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20856250

RESUMO

Attention-deficit hyperactivity disorder (ADHD) is typically characterized as a disorder of inattention and hyperactivity/impulsivity but there is increasing evidence of deficits in motivation. Using positron emission tomography (PET), we showed decreased function in the brain dopamine reward pathway in adults with ADHD, which, we hypothesized, could underlie the motivation deficits in this disorder. To evaluate this hypothesis, we performed secondary analyses to assess the correlation between the PET measures of dopamine D2/D3 receptor and dopamine transporter availability (obtained with [(11)C]raclopride and [(11)C]cocaine, respectively) in the dopamine reward pathway (midbrain and nucleus accumbens) and a surrogate measure of trait motivation (assessed using the Achievement scale on the Multidimensional Personality Questionnaire or MPQ) in 45 ADHD participants and 41 controls. The Achievement scale was lower in ADHD participants than in controls (11±5 vs 14±3, P<0.001) and was significantly correlated with D2/D3 receptors (accumbens: r=0.39, P<0.008; midbrain: r=0.41, P<0.005) and transporters (accumbens: r=0.35, P<0.02) in ADHD participants, but not in controls. ADHD participants also had lower values in the Constraint factor and higher values in the Negative Emotionality factor of the MPQ but did not differ in the Positive Emotionality factor-and none of these were correlated with the dopamine measures. In ADHD participants, scores in the Achievement scale were also negatively correlated with symptoms of inattention (CAARS A, E and SWAN I). These findings provide evidence that disruption of the dopamine reward pathway is associated with motivation deficits in ADHD adults, which may contribute to attention deficits and supports the use of therapeutic interventions to enhance motivation in ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Dopamina/fisiologia , Neurônios Dopaminérgicos/fisiologia , Mesencéfalo/fisiopatologia , Motivação/fisiologia , Núcleo Accumbens/fisiopatologia , Recompensa , Adulto , Radioisótopos de Carbono , Cocaína , Dopamina/análise , Proteínas da Membrana Plasmática de Transporte de Dopamina/análise , Neurônios Dopaminérgicos/química , Feminino , Humanos , Masculino , Mesencéfalo/química , Mesencéfalo/diagnóstico por imagem , Núcleo Accumbens/química , Núcleo Accumbens/diagnóstico por imagem , Inventário de Personalidade , Tomografia por Emissão de Pósitrons , Racloprida , Compostos Radiofarmacêuticos , Receptores de Dopamina D2/análise , Receptores de Dopamina D3/análise
12.
Mol Psychiatry ; 16(8): 818-25, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21483434

RESUMO

Positive emotionality (PEM) (personality construct of well-being, achievement/motivation, social and closeness) has been associated with striatal dopamine D2 receptor availability in healthy controls. As striatal D2 receptors modulate activity in orbitofrontal cortex (OFC) and cingulate (brain regions that process natural and drug rewards), we hypothesized that these regions underlie PEM. To test this, we assessed the correlation between baseline brain glucose metabolism (measured with positron emission tomography and [(18)F]fluoro-deoxyglucose) and scores on PEM (obtained from the multidimensional personality questionnaire or MPQ) in healthy controls (n = 47). Statistical parametric mapping (SPM) analyses revealed that PEM was positively correlated (P(c)<0.05, voxel corrected) with metabolism in various cortical regions that included orbitofrontal (Brodman area, BA 11, 47) and cingulate (BA 23, 32) and other frontal (BA 10, 9), parietal (precuneus, BA 40) and temporal (BA 20, 21) regions that overlap with the brain's default mode network (DMN). Correlations with the other two main MPQ personality dimensions (negative emotionality and constraint) were not significant (SPM P(c)<0.05). Our results corroborate an involvement of orbitofrontal and cingulate regions in PEM, which is considered a trait that protects against substance use disorders. As dysfunction of OFC and cingulate is a hallmark of addiction, these findings support a common neural basis underlying protective personality factors and brain dysfunction underlying substance use disorders. In addition, we also uncovered an association between PEM and baseline metabolism in regions from the DMN, which suggests that PEM may relate to global cortical processes that are active during resting conditions (introspection, mind wandering).


Assuntos
Mapeamento Encefálico/psicologia , Emoções/fisiologia , Lobo Frontal/fisiologia , Giro do Cíngulo/fisiologia , Vias Neurais/fisiologia , Adulto , Mapeamento Encefálico/métodos , Feminino , Lobo Frontal/diagnóstico por imagem , Giro do Cíngulo/diagnóstico por imagem , Humanos , Masculino , Vias Neurais/diagnóstico por imagem , Inventário de Personalidade , Cintilografia
13.
Acta Psychiatr Scand ; 126(2): 137-50, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22375904

RESUMO

OBJECTIVE: To examine 3-year quality-of-life (QOL) outcomes among United States adults with Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV) antisocial personality disorder (ASPD), syndromal adult antisocial behavior without conduct disorder (CD) before age 15 [adulthood antisocial behavioral syndrome (AABS), not a DSM-IV diagnosis], or no antisocial behavioral syndrome at baseline. METHOD: Face-to-face interviews (n = 34 653). Psychiatric disorders were assessed using the Alcohol Use Disorder and Associated Disabilities Interview Schedule - DSM-IV Version. Health-related QOL was assessed using the Short-Form 12-Item Health Survey, version 2 (SF-12v2). Other outcomes included past-year Perceived Stress Scale-4 (PSS-4) scores, employment, receipt of Supplemental Security Income (SSI), welfare, and food stamps, and participation in social relationships. RESULTS: Antisocial personality disorder and AABS predicted poorer employment, financial dependency, social relationship, and physical health outcomes. Relationships of antisociality to SSI and food stamp receipt and physical health scales were modified by baseline age. Both antisocial syndromes predicted higher PSS-4, AABS predicted lower SF-12v2 Vitality, and ASPD predicted lower SF-12v2 Social Functioning scores in women. CONCLUSION: Similar prediction of QOL by ASPD and AABS suggests limited utility of requiring CD before age 15 to diagnose ASPD. Findings underscore the need to improve prevention and treatment of antisocial syndromes.


Assuntos
Transtorno da Personalidade Antissocial/psicologia , Qualidade de Vida/psicologia , Adolescente , Adulto , Idoso , Distribuição de Qui-Quadrado , Emprego/psicologia , Feminino , Nível de Saúde , Humanos , Relações Interpessoais , Entrevista Psicológica , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Análise de Regressão , Estados Unidos , Adulto Jovem
14.
Biochemistry (Mosc) ; 77(5): 419-24, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22813582

RESUMO

The brain is protected by a physiological blood-brain barrier (BBB) against toxins and some metabolites circulating in the blood. At the same time, the BBB limits penetration into the brain of many neuroactive drugs. Efficient ways to increase BBB permeability for delivery of drugs of different chemical nature into the brain are unknown. This work deals with delivery into the brain of 10(-2) M dopamine, a substance that does not penetrate the BBB under normal circumstances. It was studied in two independent experiments: (i) penetration of (3)H-labeled dopamine from its mixture with 10(-5) M H2O2 into hypothalamus and striatum structures of intact rat brain, and (ii) effect of unlabeled dopamine from a mixture with H(2)O(2) on the rat motor activity in a haloperidol catalepsy model. It was shown that (i) at the third minute after nasal application of the dopamine + H(2)O(2) mixture, the dopamine level increases 45-fold in the hypothalamus and almost 30-fold in the striatum and (ii) motility of animals in the catalepsy haloperidol model is recovered 90 sec after intranasal introduction of dopamine. No such effects were observed after replacement of H(2)O(2) by 0.9% NaCl solution. Thus, it was shown on the example of dopamine that its introduction into the nasal cavity simultaneously with H(2)O(2) provides for rapid delivery of the drug into the brain. These results expand our knowledge concerning the biological role of exoROS in modulating BBB permeability and may contribute to the development of a new therapeutic strategy for neurological diseases.


Assuntos
Barreira Hematoencefálica/metabolismo , Ácido 3,4-Di-Hidroxifenilacético/análise , Administração Intranasal , Animais , Catalepsia/induzido quimicamente , Catalepsia/metabolismo , Catalepsia/patologia , Cromatografia Líquida de Alta Pressão , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Dopamina/análise , Dopamina/farmacologia , Dopaminérgicos/análise , Dopaminérgicos/farmacologia , Haloperidol/toxicidade , Peróxido de Hidrogênio/farmacologia , Hipotálamo/metabolismo , Marcação por Isótopo , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Trítio/química
15.
Plant Biol (Stuttg) ; 24(1): 3-8, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34569131

RESUMO

A plant's associated biota plays an integral role in its metabolism, nutrient uptake, stress tolerance, pathogen resistance and other physiological processes. Although a virome is an integral part of the phytobiome, a major contradiction exists between the holobiont approach and the practical need to eradicate pathogens from agricultural crops. In this review, we discuss grapevine virus control, but the issue is also relevant for numerous other crops, including potato, cassava, citrus, cacao and other species. Grapevine diseases, especially viral infections, cause main crop losses. Methods have been developed to eliminate viruses and other microorganisms from plant material, but elimination of viruses from plant material does not guarantee protection from future reinfection. Elimination of viral particles in plant material could create genetic drift, leading in turn to an increase in the occurrence of pathogenic strains of viruses. A possible solution may be a combination of virus elimination and plant propagation in tissue culture with in vitro vaccination. In this context, possible strategies to control viral infections include application of plant resistance inducers, cross protection and vaccination using siRNA, dsRNA and viral replicons during plant 'cleaning' and in vitro propagation. The experience and knowledge accumulated in human immunization can help plant scientists to develop and employ new methods of protection, leading to more sustainable and healthier crop production.


Assuntos
Vírus de Plantas , Biotecnologia , Produtos Agrícolas , Doenças das Plantas , Vacinação
16.
Br J Cancer ; 105(11): 1708-18, 2011 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-22045188

RESUMO

BACKGROUND: The best current xenograft model of multiple myeloma (MM) in immune-deficient non-obese diabetic/severe-combined immunodeficient mice is costly, animal maintenance is complex and several weeks are required to establish engraftment and study drug efficacy. More practical in vivo models may reduce time and drug development cost. We recently described a rapid low-cost xenograft model of human blood malignancies in pre-immune turkey. Here, we report application of this system for studying MM growth and the preclinical assessment of anticancer therapies. METHODS: Cell lines and MM patient cells were injected intravenously into embryonic veins on embryonic day 11 (E11). Engraftment of human cells in haematopoietic organs was detected by quantitative real-time polymerase chain reaction, immunohistochemistry, flow cytometry and circulating free light chain. RESULTS: Engraftment was detected after 1 week in all embryos injected with cell lines and in 50% of those injected with patient cells. Injection of bortezomib or lenalinomide 48 h after cell injection at therapeutic levels that were not toxic to the bone marrow dramatically reduced MM engraftment. CONCLUSION: The turkey embryo provides a practical, xenograft system to study MM and demonstrates the utility of this model for rapid and affordable testing therapeutics in vivo. With further development, this model may enable rapid, inexpensive personalised drug screening.


Assuntos
Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Mieloma Múltiplo/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Animais , Medula Óssea/efeitos dos fármacos , Ácidos Borônicos/farmacologia , Bortezomib , Linhagem Celular Tumoral , Embrião não Mamífero , Citometria de Fluxo/métodos , Humanos , Transplante de Neoplasias , Pirazinas/farmacologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Perus
17.
Am J Transplant ; 11(11): 2379-87, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21967703

RESUMO

Hepatitis C virus (HCV) causes progressive liver fibrosis in liver transplant recipients and is the principal cause of long-term allograft failure. The antifibrotic effects of sirolimus are seen in animal models but have not been described in liver transplant recipients. We reviewed 1274 liver recipients from 2002 to 2010 and identified a cohort of HCV recipients exposed to sirolimus as primary immunosuppression (SRL Cohort) and an HCV Control Group of recipients who had never received sirolimus. Yearly protocol biopsies were done recording fibrosis stage (METAVIR score) with biopsy compliance of >80% at both year one and two. In an intent-to-treat analysis, the SRL Cohort had significantly less advanced fibrosis (stage ≥2) compared to the HCV Control Group at year one (15.3% vs. 36.2%, p < 0.0001) and year two (30.1% vs. 50.5%, p = 0.001). Because sirolimus is sometimes discontinued for side effects, the SRL Cohort was subgroup stratified for sirolimus duration, showing progressively less fibrosis with longer sirolimus duration. Multivariate analysis demonstrated sirolimus as an independent predictor of minimal fibrosis at year one, and year two. This is the first study among liver transplant recipients with recurrent HCV to describe the positive impact of sirolimus in respect of reduced fibrosis extent and rate of progression.


Assuntos
Hepatite C/prevenção & controle , Transplante de Fígado/efeitos adversos , Sirolimo/uso terapêutico , Adulto , Infecções por Citomegalovirus/etiologia , Progressão da Doença , Feminino , Rejeição de Enxerto/etiologia , Hepacivirus/efeitos dos fármacos , Hepatite C/etiologia , Humanos , Terapia de Imunossupressão/métodos , Cirrose Hepática/epidemiologia , Cirrose Hepática/etiologia , Cirrose Hepática/virologia , Transplante de Fígado/patologia , Masculino , Pessoa de Meia-Idade , Sirolimo/administração & dosagem
18.
Nat Cell Biol ; 2(5): 296-301, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10806481

RESUMO

In Drosophila photoreceptors, phospholipase C (PLC) and other signalling components form multiprotein structures through the PDZ scaffold protein INAD. Association between PLC and INAD is important for termination of responses to light; the underlying mechanism is, however, unclear. Here we report that the maintenance of large amounts of PLC in the signalling membranes by association with INAD facilitates response termination, and show that PLC functions as a GTPase-activating protein (GAP). The inactivation of the G protein by its target, the PLC, is crucial for reliable production of single-photon responses and for the high temporal and intensity resolution of the response to light.


Assuntos
Proteínas de Ligação ao GTP/metabolismo , Isoenzimas/metabolismo , Fosfolipases Tipo C/metabolismo , Visão Ocular/fisiologia , Animais , Drosophila , Regulação Enzimológica da Expressão Gênica , Resposta ao Choque Térmico/fisiologia , Isoenzimas/genética , Mutagênese/fisiologia , Técnicas de Patch-Clamp , Fenótipo , Fosfolipase C beta , Estimulação Luminosa , Células Fotorreceptoras de Invertebrados/enzimologia , Fosfolipases Tipo C/genética
19.
Nat Med ; 1(7): 661-6, 1995 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7585148

RESUMO

The rapid increase in Pseudomonas (Burkholderia) cepacia infection in cystic fibrosis (CF) patients suggests epidemic transmission, but the degree of transmissibility remains controversial as conflicting conclusions have been drawn from studies at different CF centres. This report provides the first DNA sequence-based documentation of a divergent evolutionary lineage of P. cepacia associated with CF centre epidemics in North America (Toronto) and Europe (Edinburgh). The involved epidemic clone encoded and expressed novel cable (Cbl) pili that bind to CF mucin. The sequence of the cblA pilin subunit gene carried by the epidemic isolates proved to be invariant. Although it remains to be determined how many distinct, highly transmissible lineages exist, our results provide both a DNA sequence and chromosomal fingerprint that can be used to screen for one such particularly infectious, transatlantic clone.


Assuntos
Infecções por Burkholderia/epidemiologia , Burkholderia cepacia/isolamento & purificação , Infecção Hospitalar/epidemiologia , Fibrose Cística/complicações , Surtos de Doenças , Pneumonia Bacteriana/epidemiologia , Sequência de Aminoácidos , Aderência Bacteriana , Proteínas da Membrana Bacteriana Externa/genética , Infecções por Burkholderia/complicações , Infecções por Burkholderia/microbiologia , Infecções por Burkholderia/transmissão , Burkholderia cepacia/efeitos dos fármacos , Burkholderia cepacia/genética , Burkholderia cepacia/patogenicidade , Criança , Infecção Hospitalar/complicações , Infecção Hospitalar/microbiologia , Impressões Digitais de DNA , DNA Bacteriano/genética , Suscetibilidade a Doenças , Proteínas de Fímbrias , Fímbrias Bacterianas/fisiologia , Marcadores Genéticos , Hospitais Especializados , Humanos , Dados de Sequência Molecular , América do Norte/epidemiologia , Filogenia , Pneumonia Bacteriana/complicações , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/transmissão , Polimorfismo de Fragmento de Restrição , Escócia/epidemiologia , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico
20.
Ultrasound Obstet Gynecol ; 37(3): 324-7, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20812377

RESUMO

OBJECTIVE: To examine the diagnostic precision of ultrasound examination for placenta accreta in women with placenta previa and to compare the morbidity associated with accreta to that of previa alone. METHODS: This was a retrospective cohort study of all women with previa with/without accreta examined at the University of California, San Francisco (UCSF) between 2002 and 2008. The sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of ultrasound examination for the diagnosis of accreta were calculated and compared with results from similar studies in the literature. Univariable analysis was used to compare clinical outcomes. RESULTS: The PPV of an ultrasound diagnosis of accreta was 68% and NPV was 98%. Ultrasound had a sensitivity of 89.5%. Compared with previa alone, accreta had an odds ratio (OR) of 89.6 (95% CI, 19.44-412.95) for estimated blood loss > 2 L, an OR of 29.6 (95% CI, 8.20-107.00) for transfusion and an OR of 8.52 (95% CI, 2.58-28.11) for length of hospital stay > 4 days. CONCLUSION: Placenta accreta is associated with greater morbidity than is placenta previa alone. Ultrasound examination is a good diagnostic test for accreta in women with placenta previa. This is consistent with most other studies in the literature.


Assuntos
Recesariana/efeitos adversos , Placenta Acreta/diagnóstico por imagem , Placenta Prévia/diagnóstico por imagem , Hemorragia Pós-Parto/diagnóstico por imagem , Estudos de Coortes , Feminino , Humanos , Histerectomia , Placenta Acreta/etiologia , Placenta Prévia/etiologia , Hemorragia Pós-Parto/etiologia , Valor Preditivo dos Testes , Gravidez , Estudos Retrospectivos , Fatores de Risco , São Francisco , Sensibilidade e Especificidade , Ultrassonografia Pré-Natal/métodos
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