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1.
Neuropathol Appl Neurobiol ; 43(5): 409-418, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27664944

RESUMO

INTRODUCTION: Microinfarcts, small ischaemic foci common in ageing brain, are associated with dementia and gait dysfunction. We determined their relationship with dementia, mobility and cerebrovascular disease in an older population-representative brain donor cohort. These data on microinfarcts were evaluated in relation to pathological assessments of clinically significant cerebral small vessel disease (SVD). METHODS: Microinfarcts were assessed in the MRC Cognitive Function and Ageing Study (n = 331). Nine brain areas were staged according to the number of areas affected. RESULTS: 36% of brains showed at least 1 microinfarct. Higher cortical microinfarct stage was associated with dementia at death (OR 1.41, 95% CI 1.02; 1.96, P = 0.038), whilst cortical and subcortical microinfarct stages were associated with impaired mobility (OR 1.36, 95% CI 1.05-1.74; P 0.018) and falls (OR 1.96, 95% CI 1.11-3.43; P = 0.02). Adding data on microinfarcts to a definition of SVD, based on white matter lesions (WMLs), lacunes and significant arteriosclerosis, were assessed by comparing area under ROC curve (AUC) with and without microinfarcts. SVD was significantly related to dementia status with or without inclusion of microinfarcts. Modelling potential pathological definitions of SVD to predict dementia or impaired mobility indicated optimal prediction using combined assessment of WMLs, lacunes and microinfarcts. CONCLUSION: Cortical (dementia) and subcortical microinfarcts (impaired mobility) are related to diverse clinical outcomes. Optimal pathological assessment of significant SVD in brain ageing is achieved based on WMLs, lacunes and microinfarcts and may not require subjective assessment of the extent and severity of arteriosclerosis.


Assuntos
Infarto Encefálico/epidemiologia , Encéfalo/patologia , Doenças de Pequenos Vasos Cerebrais/patologia , Idoso , Idoso de 80 Anos ou mais , Autopsia , Estudos de Coortes , Demência/epidemiologia , Demência/patologia , Feminino , Humanos , Masculino , Limitação da Mobilidade , Prevalência
2.
Faraday Discuss ; 200: 75-100, 2017 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-28581558

RESUMO

Halogens (Cl, Br) have a profound influence on stratospheric ozone (O3). They (Cl, Br and I) have recently also been shown to impact the troposphere, notably by reducing the mixing ratios of O3 and OH. Their potential for impacting regional air-quality is less well understood. We explore the impact of halogens on regional pollutants (focussing on O3) with the European grid of the GEOS-Chem model (0.25° × 0.3125°). It has recently been updated to include a representation of halogen chemistry. We focus on the summer of 2015 during the ICOZA campaign at the Weybourne Atmospheric Observatory on the North Sea coast of the UK. Comparisons between these observations together with those from the UK air-quality network show that the model has some skill in representing the mixing ratios/concentration of pollutants during this period. Although the model has some success in simulating the Weybourne ClNO2 observations, it significantly underestimates ClNO2 observations reported at inland locations. It also underestimates mixing ratios of IO, OIO, I2 and BrO, but this may reflect the coastal nature of these observations. Model simulations, with and without halogens, highlight the processes by which halogens can impact O3. Throughout the domain O3 mixing ratios are reduced by halogens. In northern Europe this is due to a change in the background O3 advected into the region, whereas in southern Europe this is due to local chemistry driven by Mediterranean emissions. The proportion of hourly O3 above 50 nmol mol-1 in Europe is reduced from 46% to 18% by halogens. ClNO2 from N2O5 uptake onto sea-salt leads to increases in O3 mixing ratio, but these are smaller than the decreases caused by the bromine and iodine. 12% of ethane and 16% of acetone within the boundary layer is oxidised by Cl. Aerosol response to halogens is complex with small (∼10%) reductions in PM2.5 in most locations. A lack of observational constraints coupled to large uncertainties in emissions and chemical processing of halogens make these conclusions tentative at best. However, the results here point to the potential for halogen chemistry to influence air quality policy in Europe and other parts of the world.

3.
Neuropathol Appl Neurobiol ; 40(3): 258-69, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23678850

RESUMO

INTRODUCTION: Magnetic resonance imaging (MRI) cerebral microbleeds (CMB) arise from ferromagnetic haemosiderin iron assumed to derive from extravasation of erythrocytes. Light microscopy of ageing brain frequently reveals foci of haemosiderin from single crystalloids to larger, predominantly perivascular, aggregates. The pathological and radiological relationship between these findings is not resolved. METHODS: Haemosiderin deposition and vascular pathology in the putamen were quantified in 200 brains donated to the population-representative Medical Research Council Cognitive Function and Ageing Study. Molecular markers of gliosis and tissue integrity were assessed by immunohistochemistry in brains with highest (n = 20) and lowest (n = 20) levels of putamen haemosiderin. The association between haemosiderin counts and degenerative and vascular brain pathology, clinical data, and the haemochromatosis (HFE) gene H63D genotype were analysed. The frequency of MRI CMB in 10 cases with highest and lowest burden of putamen haemosiderin, was compared using post mortem 3T MRI. RESULTS: Greater putamen haemosiderin was significantly associated with putaminal indices of small vessel ischaemia (microinfarcts, P < 0.05; arteriolosclerosis, P < 0.05; perivascular attenuation, P < 0.001) and with lacunes in any brain region (P < 0.023) but not large vessel disease, or whole brain measures of neurodegenerative pathology. Higher levels of putamen haemosiderin correlated with more CMB (P < 0.003). CONCLUSIONS: The MRI-CMB concept should take account of brain iron homeostasis, and small vessel ischaemic change in later life, rather than only as a marker for minor episodes of cerebrovascular extravasation. These data are of clinical relevance, suggesting that basal ganglia MRI microbleeds may be a surrogate for ischaemic small vessel disease rather than exclusively a haemorrhagic diathesis.


Assuntos
Isquemia Encefálica/patologia , Encéfalo/patologia , Hemossiderina/análise , Putamen/patologia , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Putamen/química
4.
Water Sci Technol ; 69(4): 775-82, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24569276

RESUMO

The most widely used methods for sludge blanket measurements are based on acoustic or optic principles. In operation, both methods are expensive and often maintenance-intensive. Therefore a novel, reliable and simple method for sludge blanket measurement is proposed. It is based on the differential pressure measurement in the sludge zone compared with the differential pressure in the clear water zone, so that it is possible to measure the upper and the lower sludge level in a tank. Full-scale tests of this method were done in the secondary clarifier at the waste water treatment plant in Hecklingen, Germany. The result shows a good approximation of the manually measured sludge level.


Assuntos
Reatores Biológicos , Esgotos , Arquitetura de Instituições de Saúde , Modelos Teóricos , Fatores de Tempo
5.
Neuropathol Appl Neurobiol ; 39(7): 788-99, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23421725

RESUMO

AIMS: Calcium dyshomeostasis is implicated in the pathogenesis of several neurodegenerative disorders including Alzheimer's disease. However, much of the previous research has focused on changes in neuronal calcium signalling. In a recent microarray study we identified dysregulation of several key signalling pathways including the Ca(2+) signalling pathway in astrocytes as Alzheimer-type pathology developed. In this study we sought to determine the expression of calpain-10 and calcium/calmodulin-dependent kinase alpha (CamKIIα) in relation to Alzheimer-type pathology in a population-based study. METHODS: Using post mortem temporal cortex samples derived from the Medical Research Council Cognitive Function and Ageing Study (MRC-CFAS) ageing brain cohort we examined calpain-10 and CamKIIα gene and protein expression using quantitative polymerase chain reaction and immunohistochemistry. RESULTS: We demonstrate that astrocytic expression of calpain-10 is up-regulated, and CamKIIα down-regulated with increasing Braak stage. Using immunohistochemistry we confirm protein expression of calpain-10 in astrocytes throughout the temporal cortex and demonstrate that calpain-10 immunoreactivity is correlated with both local and global measures of Alzheimer-type pathology. In addition, we identify a subpopulation of calpain-10 immunoreactive interlaminar astrocytes that extend processes deep into the cortex. CamKIIα is predominantly neuronal in localization and is associated with the presence of diffuse plaques in the ageing brain. DISCUSSION: Dysregulated expression of key calcium signalling molecules occurs with progression of Alzheimer-type pathology in the ageing brain, highlighting the need for further functional studies of astrocytic calcium signalling with respect to disease progression.


Assuntos
Envelhecimento , Doença de Alzheimer/patologia , Astrócitos/metabolismo , Encéfalo/patologia , Cálcio/metabolismo , Adolescente , Adulto , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios/metabolismo , Placa Amiloide/metabolismo , Adulto Jovem
6.
HNO ; 61(2): 102-7, 2013 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-23241856

RESUMO

Dynamic rehabilitation of vocal fold paralysis (VFP) should receive more emphasis in the future. In unilateral immobility with signs of atrophy and wide glottal gap, non-selective reinnervation with ansa cervicalis may become an alternative to augmentation and thyroplasty. For bilateral VFP progress has been made in the concepts of selective reinnervation and neurostimulation (pacing). These new therapies have the potential to restore near normal respiration-without compromising the voice quality-and may contribute to the development of larynx transplantation surgery.


Assuntos
Terapia por Estimulação Elétrica/métodos , Laringoplastia/tendências , Regeneração Nervosa , Nervos Periféricos/transplante , Paralisia das Pregas Vocais/terapia , Prega Vocal/cirurgia , Distúrbios da Voz/terapia , Humanos , Paralisia das Pregas Vocais/complicações , Prega Vocal/inervação , Distúrbios da Voz/etiologia
7.
Pneumologie ; 66(4): 212-7, 2012 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-22477481

RESUMO

BACKGROUND: PET/CT investigation with 18F-fluorodeoxyglucose (FDG) has a high sensitivity (89 - 100 %) and good specificity (79 - 95 %) for the diagnosis of NSCLC. Currently, it is mainly used in preoperative staging. This leads in approximately 15 % of these cases to the diagnosis of metastatic disease that was neither clinically suspected nor seen in previously performed conventional imaging. We hypothesised that including these cases in the palliative stage IV group would have an influence on overall survival. AIM: The aim of this study was to compare the overall survival (OS) of patients with stage IV NSCLC who underwent FDG-PET/CT staging with patients in whom conventional imaging procedures were performed. METHODS: We analysed the OS of all stage IV NSCLC patients diagnosed in our clinic in 2009 (n = 254), 96/254 (38 %) patients were staged with PET/CT and 158/254 (62 %) with conventional imaging (CT group). Survival data were compared by Kaplan-Meier statistics. RESULTS: Patients in the PET/CT group were younger (65 ± 11) than in the CT group (68 ± 10 years; p = 0.008). The median OS of all patients was 246 (range: 217 - 275) days; 338 (range: 247 - 429) days in the PET/CT group and 207 (range: 161 - 253) days in the CT group (p = 0.001), stating a difference of 131 days (4.4 months) in median OS. CONCLUSION: The use of FDG-PET/CT staging mainly in the preoperative setting leads to stage migration of patients with a better prognosis into the worst stage (IV) and thus longer survival within this subgroup. This survival benefit is unrelated to treatment and needs to be addressed in future studies.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Fluordesoxiglucose F18 , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Tomografia por Emissão de Pósitrons/estatística & dados numéricos , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prevalência , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Sensibilidade e Especificidade , Análise de Sobrevida , Taxa de Sobrevida
8.
Neuropathol Appl Neurobiol ; 36(1): 25-40, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19422529

RESUMO

AIMS: Increasing evidence suggests a role for oxidative damage to DNA in brain ageing and in neurodegenerative disorders, including Alzheimer's disease. Most studies have focussed on the reduced capacity for DNA repair by neurones, and have not taken into account the effect of oxidative stress on astrocytes, and their contribution to pathology. METHODS: We examined levels of oxidative stress, DNA damage and DNA repair mechanisms in astrocytes in a population-based sample derived from the Medical Research Council Cognitive Function and Ageing Neuropathology Study. RESULTS: We demonstrate wide variation in parameters for oxidative stress and DNA damage in astrocytes in the ageing population. We show that there is a significant reduction (P = 0.002) in the lipid peroxidation marker malondialdehyde with increasing Braak stage in Alzheimer's disease. Furthermore, we demonstrate that expression of the DNA damage-associated molecules H2AX and DNA-dependent protein kinase do not increase with increasing Braak stage, rather there is evidence of a nonsignificant reduction in DNA-dependent protein kinase expression by neurones and astrocytes, and in H2AX by neurones with increasing levels of Alzheimer's type pathology. CONCLUSIONS: These findings suggest that the changes in oxidative stress and the astrocyte DNA damage response are not accounted for as an accumulating effect due to established Alzheimer-type pathology. We hypothesize that astrocyte damage, leading to impaired function, may contribute to the development of ageing brain pathology in some individuals.


Assuntos
Envelhecimento/patologia , Astrócitos/patologia , Encéfalo/patologia , Dano ao DNA/fisiologia , Estresse Oxidativo/fisiologia , 8-Hidroxi-2'-Desoxiguanosina , Idoso , Doença de Alzheimer/patologia , Astrócitos/metabolismo , Western Blotting , Proteína Quinase Ativada por DNA/biossíntese , Desoxiguanosina/análogos & derivados , Desoxiguanosina/biossíntese , Histonas/biossíntese , Humanos , Imuno-Histoquímica , Neurônios/metabolismo , Neurônios/patologia
9.
Brain ; 132(Pt 5): 1324-34, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19321462

RESUMO

Deposits of abnormally phosphorylated tau protein are found in numerous neurodegenerative disorders; the 'tauopathies', which include Alzheimer's and Pick's diseases, but tau pathology is also found in the ageing brain. Variation in tau pathology in brain ageing and its relationship to development of tauopathies and cognitive impairment remains unclear. We aimed to determine the extent and pattern of spread of tau pathology in the hippocampus, a susceptible region important in dementia and milder states of memory impairment, using hippocampal samples from the elderly population-based Medical Research Council Cognitive Function and Ageing Study neuropathology cohort. Tau deposition was assessed in hippocampal anatomical sub-regions using the AT8 antibody to phosphorylated tau and isoform-specific antibodies to 3 and 4-repeat tau (RD3 and RD4). Abeta pathology was also assessed. In this population sample, which includes the full ageing spectrum from individuals with no cognitive impairment to those with dementia satisfying clinico-pathology criteria for Alzheimer's disease, we have demonstrated a high prevalence at death of tau pathology. AT8, Abeta, RD3 and RD4 showed similar regional distribution and increased RD3 was noted in late-stage ghost tangles. Abeta was shown to be a poor explanatory variable for tau pathology. Tau deposition progressed in a hierarchical manner. Hippocampal input regions and projection zones (such as lateral entorhinal cortex, CA1/subiculum border and outer molecular layer of dentate) were initially affected, with anterograde progression though the hippocampal circuitry. Six hippocampal tau anatomical stages were defined, each linking projectionally to their adjacent stages, suggesting spread of tau malfunction through neuroanatomical pathways in hippocampal ageing. These stages were significantly associated with dementia, and may provide a clinically useful tool in the clinico-pathological assessment of dementia and mild cognitive impairment.


Assuntos
Envelhecimento/metabolismo , Doença de Alzheimer/metabolismo , Hipocampo/química , Proteínas tau/análise , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/patologia , Envelhecimento/psicologia , Doença de Alzheimer/patologia , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/análise , Peptídeos beta-Amiloides/metabolismo , Distribuição de Qui-Quadrado , Cognição , Progressão da Doença , Córtex Entorrinal/química , Córtex Entorrinal/metabolismo , Córtex Entorrinal/patologia , Feminino , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Imuno-Histoquímica , Estudos Longitudinais , Masculino , Vias Neurais/fisiologia , Proteínas tau/metabolismo
10.
Philos Trans R Soc Lond B Biol Sci ; 375(1810): 20190513, 2020 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-32892733

RESUMO

During the summer of 2018, a widespread drought developed over Northern and Central Europe. The increase in temperature and the reduction of soil moisture have influenced carbon dioxide (CO2) exchange between the atmosphere and terrestrial ecosystems in various ways, such as a reduction of photosynthesis, changes in ecosystem respiration, or allowing more frequent fires. In this study, we characterize the resulting perturbation of the atmospheric CO2 seasonal cycles. 2018 has a good coverage of European regions affected by drought, allowing the investigation of how ecosystem flux anomalies impacted spatial CO2 gradients between stations. This density of stations is unprecedented compared to previous drought events in 2003 and 2015, particularly thanks to the deployment of the Integrated Carbon Observation System (ICOS) network of atmospheric greenhouse gas monitoring stations in recent years. Seasonal CO2 cycles from 48 European stations were available for 2017 and 2018. Earlier data were retrieved for comparison from international databases or national networks. Here, we show that the usual summer minimum in CO2 due to the surface carbon uptake was reduced by 1.4 ppm in 2018 for the 10 stations located in the area most affected by the temperature anomaly, mostly in Northern Europe. Notwithstanding, the CO2 transition phases before and after July were slower in 2018 compared to 2017, suggesting an extension of the growing season, with either continued CO2 uptake by photosynthesis and/or a reduction in respiration driven by the depletion of substrate for respiration inherited from the previous months due to the drought. For stations with sufficiently long time series, the CO2 anomaly observed in 2018 was compared to previous European droughts in 2003 and 2015. Considering the areas most affected by the temperature anomalies, we found a higher CO2 anomaly in 2003 (+3 ppm averaged over 4 sites), and a smaller anomaly in 2015 (+1 ppm averaged over 11 sites) compared to 2018. This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'.


Assuntos
Atmosfera/análise , Ciclo do Carbono , Dióxido de Carbono/análise , Secas , Ecossistema , Europa (Continente)
11.
Ann Oncol ; 20(4): 666-73, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19153121

RESUMO

BACKGROUND: To compare capecitabine/cisplatin with 5-fluorouracil/cisplatin as first-line treatment for advanced gastric cancer (AGC). PATIENTS AND METHODS: In this randomised, open-label, phase III study, patients received cisplatin (80 mg/m(2) i.v. day 1) plus oral capecitabine (1000 mg/m(2) b.i.d., days 1-14) (XP) or 5-FU (800 mg/m(2)/day by continuous infusion, days 1-5) (FP) every 3 weeks. The primary end point was to confirm noninferiority of XP versus FP for progression-free survival (PFS). RESULTS: A total of 316 patients were randomised to XP (n = 160) or FP (n = 156). In the per-protocol population, median PFS for XP (n = 139) versus FP (n = 137) was 5.6 versus 5.0 months. The primary end point was met with an unadjusted hazard ratio (HR) of 0.81 [95% confidence interval (CI) 0.63-1.04, P < 0.001 versus noninferiority margin of 1.25]. Median overall survival was 10.5 versus 9.3 months for XP versus FP (unadjusted HR = 0.85, 95% CI 0.64-1.13, P = 0.008 versus noninferiority margin of 1.25). The most common treatment-related grade 3/4 adverse events in XP versus FP patients were as follows: neutropenia (16% versus 19%), vomiting (7% versus 8%), and stomatitis (2% versus 6%). CONCLUSIONS: XP showed significant noninferiority for PFS versus FP in the first-line treatment of AGC. XP can be considered an effective alternative to FP.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida
12.
Neuroscience ; 158(2): 845-55, 2009 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-19010398

RESUMO

Stress induced by early life social isolation leads to long-lasting alterations in stress responses and serotonergic activity. Corticotropin-releasing factor (CRF) is a neurotransmitter that mediates stress responses and alters serotonergic activity. We tested the hypothesis that the stress of early life isolation enhances responses to CRF in adulthood by determining the effect of CRF infusions into the dorsal raphe nucleus (dRN) on 5-HT release in the nucleus accumbens (NAc) of adult rats using in vivo microdialysis. Juvenile male rats were either isolated or housed in groups of three for a 3-week period beginning on postnatal day 21 after which, all rats were group-reared for an additional 2 weeks. Following the isolation/re-socialization procedure, infusion of 100 ng CRF into the dRN decreased 5-HT release in the NAc of group-reared rats. This treatment did not significantly affect 5-HT release in the NAc of isolation-reared animals. In contrast, infusion of 500 ng CRF into the dRN transiently increased 5-HT release in the NAc of both group-reared and isolated animals with isolated animals showing a more prolonged serotonergic response. Western blot and immunofluorescent staining for CRF receptors in the dRN showed that CRF(2) receptor levels were increased in the dRN of isolation-reared animals when compared with group-reared rats. Taken together, the results suggest that isolation during the early part of development causes alterations in both CRF receptor levels and CRF-mediated serotonergic activity. These effects may underlie the increased sensitivity to stress observed in isolates.


Assuntos
Hormônio Liberador da Corticotropina/farmacologia , Hormônios/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Isolamento Social/psicologia , Animais , Animais Recém-Nascidos , Comportamento Animal , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica em Archaea/efeitos dos fármacos , Regulação da Expressão Gênica em Archaea/fisiologia , Masculino , Microdiálise , Ratos , Ratos Sprague-Dawley , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Serotonina/metabolismo
13.
Neuroscience ; 158(2): 412-25, 2009 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-18992791

RESUMO

Salmonids establish social hierarchies as a result of aggressive social interactions. The establishment of dominant or subordinate status is strongly linked to neuroendocrine responses mediated through the stress axis. In this study, we tested the effects of introcerebroventricular (icv) corticotropin releasing factor (CRF) on the behavioral outcome, plasma cortisol and monoamine function in trout subjected to a socially aggressive encounter. Rainbow trout were treated with an icv injection of artificial cerebrospinal fluid (aCSF), 500 or 2000 ng ovine CRF, or not injected. Fish were allowed to interact with a similarly sized conspecific for 15 min. Following the behavioral interaction, plasma cortisol and central monoamine concentrations were analyzed. Trout treated with CRF were victorious in approximately 66% of the aggressive encounters against aCSF-treated opponents. Trout injected with CRF exhibited a reduction in the total number of attacks and decreased latency to attack. When trout were divided into winners and losers, only victorious CRF-treated fish exhibited a reduced latency to attack and fewer retreats. Social stress increased cortisol levels in both winners and losers of aggressive interaction. This effect was enhanced with the additional stress incurred from icv injection of aCSF. However, icv CRF in addition to social stress decreased plasma cortisol in both winners and losers. While aggression stimulated significant changes in serotonergic and dopaminergic activity, the magnitude and direction were dependent on limbic brain region, CRF dose, and outcome of social aggression. With broad effects on aggressive behavior, anxiety, stress responsiveness, and central monoaminergic activity, CRF plays an important role in modulating the behavioral components of social interaction.


Assuntos
Agressão/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Monoaminas Biogênicas/metabolismo , Hormônio Liberador da Corticotropina/farmacologia , Reação de Fuga/efeitos dos fármacos , Análise de Variância , Animais , Encéfalo/anatomia & histologia , Encéfalo/metabolismo , Química Encefálica/efeitos dos fármacos , Hormônio Liberador da Corticotropina/metabolismo , Relação Dose-Resposta a Droga , Hierarquia Social , Hidrocortisona/sangue , Injeções Intraventriculares/métodos , Relações Interpessoais , Oncorhynchus mykiss , Tempo de Reação/efeitos dos fármacos
14.
Dement Geriatr Cogn Disord ; 27(5): 465-73, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19420941

RESUMO

BACKGROUND: The cellular pathology of astrocytes in brain ageing and their role in modulating the brain's response to neurodegenerative pathology remain incompletely understood. METHODS: Using quantitative ELISA, we have investigated glial fibrillary acidic protein (GFAP) expression in the population-based neuropathology cohort of the Medical Research Council Cognitive Function and Ageing Study to determine: (1) the population variation in the astroglial hypertrophic response, (2) its relationship to the presence of Alzheimer-type pathology, and (3) its association with cognition. RESULTS: Increasing GFAP was found with increasing Braak stage, levels increasing even at early stages. Within Braak stages, GFAP did not differ between demented and non-demented individuals, but there was greater variance in GFAP in the demented. Possession of ApoE epsilon4 was associated with slightly increased GFAP levels (not significant) for given amyloid beta protein loads. CONCLUSION: In a population-based sample, increasing gliosis precedes development of Alzheimer lesions. Population variation in GFAP with varying Alzheimer lesion burdens suggests that they are not the only driver for astrogliosis. GFAP was not independently predictive of dementia, but the variation in astrocytic responses may be a factor modulating brain responses to neurodegenerative pathology.


Assuntos
Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Química Encefálica/fisiologia , Encéfalo/crescimento & desenvolvimento , Demência/metabolismo , Demência/patologia , Proteína Glial Fibrilar Ácida/metabolismo , Idoso , Envelhecimento/fisiologia , Doença de Alzheimer/genética , Peptídeos beta-Amiloides/metabolismo , Apolipoproteína E4/metabolismo , Astrócitos/patologia , Química Encefálica/genética , Estudos de Coortes , Demência/genética , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Genótipo , Gliose/patologia , Humanos , Imuno-Histoquímica , Masculino
15.
Int J STD AIDS ; 20(11): 799-800, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19833696

RESUMO

Chain of evidence (COE) sampling is a legal concept demonstrating the journey of a sample from origin to court. Positive sexually transmitted infection (STI) results may have importance in criminal proceedings and require a demonstrated COE for them to be used as admissible evidence. A retrospective case-notes review of female sexual assault patients was carried out to review COE sampling in two clinics. Three hundred and eighteen patients underwent sexual health screening and COE sampling was indicated in 58 (18%). COE sampling was carried out in 44 (92%) of 48 indicated cases at the Haven (a dedicated sexual assault centre) and five (50%) of 10 at the Ambrose King Centre (a sexual health clinic). COE protocols should be in place in both sexual assault referral centres and sexual health clinics. In specialist clinics, with well-established guidelines and trained dedicated staff, COE sampling standards can be achieved.


Assuntos
Auditoria Clínica , Busca de Comunicante/métodos , Delitos Sexuais/legislação & jurisprudência , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/transmissão , Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Manejo de Espécimes , Reino Unido
16.
Pharmazie ; 64(2): 142-4, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19320289

RESUMO

A new flavonol glycoside, kaempferol-3,4'-di-O-beta-glucopyranoside-7-O-alpha-rhamno-pyranoside, was isolated from the ethanolic extract of the whole fresh plant of Iberis amara L., an European plant used in gastrointestinal medicine. The structure was established by a combination of 1D and 2D NMR techniques (COSY, HSQC, HMBC, NOESY) as well as UV, IR and mass spectral data.


Assuntos
Brassicaceae/química , Flavonoides/química , Cromatografia Líquida de Alta Pressão , Flavonoides/isolamento & purificação , Espectroscopia de Ressonância Magnética , Extratos Vegetais/química , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta
17.
Int J STD AIDS ; 19(8): 557-8, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18663045

RESUMO

Mental health issues following sexual assault in young people are common but early intervention may improve outcome. A retrospective case-note review of 58 female patients aged between 13 and 18 attending The Haven Whitechapel, a sexual assault referral centre, demonstrated past emotional problems in 72% of those seen, and current emotional problems in 95% of those being followed up. Fifteen percent were already involved with adolescent mental health services (AMHS). All patients requiring and not already receiving input were referred to AMHS or in-house. Of 23 patients referred to AMHS, eight (35%) were accepted and the patients attended, seven (30%) were accepted but did not attend, six (26%) were declined and the outcome of two referrals was unknown. The prevalence of emotional problems and inconsistent referral outcomes demonstrate a need for closer links with AMHS, clearer referral criteria and improved referral pathways.


Assuntos
Serviços de Saúde do Adolescente , Transtornos Mentais/epidemiologia , Serviços de Saúde Mental , Encaminhamento e Consulta , Delitos Sexuais , Adolescente , Serviços de Saúde do Adolescente/estatística & dados numéricos , Humanos , Transtornos Mentais/etiologia , Transtornos Mentais/terapia , Serviços de Saúde Mental/estatística & dados numéricos , Prevalência , Encaminhamento e Consulta/estatística & dados numéricos , Delitos Sexuais/psicologia
18.
Int J STD AIDS ; 19(7): 482-3, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18574123

RESUMO

Survivors of sexual assault can access treatment and care within genitourinary (GU) medicine services by attending walk-in, booked or a dedicated clinic. Haven Whitechapel the local Sexual Assault Referral Centre (SARC) provides a forensic and aftercare service. A team was set up to ensure efficient communication and clear referral pathways between the centres. This service was audited after eight months of joint working. A retrospective case note review of women attending between August and March 2007 was undertaken. Sixty-nine women were referred to the dedicated clinic. Vaginal rape was reported by 80% of the women. Offer of forensic medical examination documented in 71% presenting within the forensic timeframe. Emergency contraception was offered to 75% of the women. HIV-acquisition risk was documented in 70%. Seventy-eight percent had a sexually transmitted infection screen at their first visit. An HIV test was done to 41% of the women; all were found to be negative. Sixty-two percent women attended follow-up. GU medicine staff should receive specific training in sexual assault. We recommend that GU medicine services and SARC work in partnership to improve the care of victims of sexual assault who access general GU medicine services.


Assuntos
Instituições de Assistência Ambulatorial/estatística & dados numéricos , Delitos Sexuais/psicologia , Delitos Sexuais/estatística & dados numéricos , Infecções Sexualmente Transmissíveis/prevenção & controle , Sobreviventes/estatística & dados numéricos , Adolescente , Adulto , Anticoncepção Pós-Coito , Feminino , Doenças Urogenitais Femininas/diagnóstico , Doenças Urogenitais Femininas/prevenção & controle , Infecções por HIV/diagnóstico , Infecções por HIV/prevenção & controle , Humanos , Londres , Pessoa de Meia-Idade , Estupro/estatística & dados numéricos , Medição de Risco , Infecções Sexualmente Transmissíveis/diagnóstico
19.
Phys Rev E ; 97(4-1): 043210, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29758670

RESUMO

The ion-ion dynamical structure factor and the equation of state of warm dense aluminum in a two-temperature quasiequilibrium state, with the electron temperature higher than the ion temperature, are investigated using molecular-dynamics simulations based on ion-ion pair potentials constructed from a neutral pseudoatom model. Such pair potentials based on density functional theory are parameter-free and depend directly on the electron temperature and indirectly on the ion temperature, enabling efficient computation of two-temperature properties. Comparison with ab initio simulations and with other average-atom calculations for equilibrium aluminum shows good agreement, justifying a study of quasiequilibrium situations. Analyzing the van Hove function, we find that ion-ion correlations vanish in a time significantly smaller than the electron-ion relaxation time so that dynamical properties have a physical meaning for the quasiequilibrium state. A significant increase in the speed of sound is predicted from the modification of the dispersion relation of the ion acoustic mode as the electron temperature is increased. The two-temperature equation of state including the free energy, internal energy, and pressure is also presented.

20.
Int J STD AIDS ; 18(1): 61-2, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17326866

RESUMO

A regional audit was undertaken to evaluate current practice in the management of survivors of sexual assault (SA) seen in genitourinary (GU) medicine clinics in the North Thames. The majority of the survivors were women. Most were fast-tracked, or seen in dedicated SA clinics. Over 60% of staff had specific training in management of SA. Core services provided included screening and treatment for sexually transmitted infections, emotional support, emergency contraception and hepatitis B vaccination. The sexual health needs of these survivors of SA are being met by most clinics. The development and use of a standardized care proforma across the region may be a means to further improve the care provided.


Assuntos
Anticoncepção Pós-Coito , Estupro , Infecções Sexualmente Transmissíveis/terapia , Apoio Social , Adolescente , Adulto , Instituições de Assistência Ambulatorial , Inglaterra , Feminino , Ginecologia , Humanos , Masculino , Infecções Sexualmente Transmissíveis/diagnóstico , Inquéritos e Questionários , Urologia
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