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1.
Intern Med J ; 53(4): 540-549, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-34668307

RESUMO

BACKGROUND: There is an absence of clinically relevant epidemiological data in regional Australia pertaining to haematological malignancies. AIM: To determine the incidence and geographical variation of haematological malignancies in North Queensland using a clinically appropriate disease classification. METHODS: Retrospective, observational study of individual patient data records of all adults diagnosed with a haematological malignancy between 2005 and 2014 and residing within The Townsville Hospital Haematology catchment region. We report descriptive summaries, incidence rates and incidence-rate ratios of haematological malignancies by geographic regions. RESULTS: One thousand, five hundred and eighty-one haematological malignancies (69% lymphoid, 31% myeloid) were diagnosed over the 10-year study period. Descriptive data are presented for 58 major subtypes, as per the WHO diagnostic classification of tumours of haemopoietic and lymphoid tissues. The overall median age at diagnosis was 66 years with a male predominance (60%). We demonstrate a temporal increase in the incidence of haematological malignancies over the study period. We observed geographical variations in the age-standardised incidence rates per 100 000 ranging from 0.5 to 233.5. Our data suggest an increased incidence rate ratio for haematological malignancies in some postcodes within the Mackay area compared with other regions. CONCLUSION: The present study successfully reports on the incidence of haematological malignancies in regional Queensland using a clinically meaningful diagnostic classification system and identifies potential geographic hotspots. We advocate for such contemporary, comprehensive and clinically meaningful epidemiological data reporting of blood cancer diagnoses in wider Australia. Such an approach will have significant implications towards developing appropriate data-driven management strategies and public health responses for haematological malignancies.


Assuntos
Neoplasias Hematológicas , Neoplasias , Adulto , Humanos , Masculino , Idoso , Feminino , Estudos Retrospectivos , Queensland/epidemiologia , Neoplasias Hematológicas/epidemiologia , Neoplasias/epidemiologia , Incidência
2.
Intern Med J ; 50(2): 214-221, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32037713

RESUMO

BACKGROUND: The Townsville Hospital is a tertiary hospital in North Queensland with one of the largest regional transplant centres in Australia, performing primarily autologous haemopoietic stem cell transplants (HSCT) for various haematological malignancies. AIMS: This single-centre, retrospective, observational study aims to describe the activity and outcomes of autologous HSCT at The Townsville Hospital between 2003 and 2017 to verify safety standards. METHODS: Patient-level data were collected, including demographics, frequency and indication for transplant, conditioning, current clinical status and cause of death. Key outcomes included overall survival, non-relapse mortality, incidence of therapy-related neoplasm and causes of death. Progression-free survival in the multiple myeloma (MM) subgroup was also assessed. RESULTS: There were 319 autologous HSCT in 286 patients, with a median age of 58 years (range 14-71 years); 62% of patients were male. Indications for transplantation were: MM 53.7%, non-Hodgkin lymphoma 29.4%, Hodgkin lymphoma 5.0% and other 11.9%. Causes of death were: disease progression/relapse (65.2%), second malignancy (17.0%), infection (9.8%) and other (8.0%). Non-relapse mortality was 1.2% (95% confidence interval 0.4-3.0) and 3.2% (1.7-5.7) at 100 days and 1 year, respectively, post-HSCT. Overall survival at 2 years was 81.0% (73.8-86.4) for MM and 69.6% (58.8-78.1) for non-Hodgkin lymphoma. The median progression-free survival in the MM cohort was 3.3 years. CONCLUSION: The Townsville Hospital transplant centre provides an important transplant service in regional Queensland, with outcomes comparable to national data. We reported a relatively high rate of second malignancy as a cause of death.


Assuntos
Transplante de Células-Tronco Hematopoéticas/mortalidade , Doença de Hodgkin/cirurgia , Linfoma não Hodgkin/cirurgia , Mieloma Múltiplo/cirurgia , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Queensland/epidemiologia , Estudos Retrospectivos , Transplante Autólogo , Adulto Jovem
3.
Neuroimage Clin ; 22: 101776, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30927605

RESUMO

BACKGROUND: Effects of beta-amyloid accumulation on neuronal function precede the clinical manifestation of Alzheimer's disease (AD) by years and affect distinct cognitive brain networks. As previous studies suggest a link between beta-amyloid and dysregulation of excitatory and inhibitory neurotransmitters, we aimed to investigate the impact of GABA and glutamate on beta-amyloid related functional connectivity. METHODS: 29 cognitively unimpaired old-aged adults (age = 70.03 ±â€¯5.77 years) were administered 11C-Pittsburgh Compound B (PiB) positron-emission tomography (PET), and MRI at 7 Tesla (7T) including blood oxygen level dependent (BOLD) functional MRI (fMRI) at rest for measuring static and dynamic functional connectivity. An advanced 7T MR spectroscopic imaging (MRSI) sequence based on the free induction decay acquisition localized by outer volume suppression' (FIDLOVS) technology was used for gray matter specific measures of GABA and glutamate in the posterior cingulate and precuneus (PCP) region. RESULTS: GABA and glutamate MR-spectra indicated significantly higher levels in gray matter than in white matter. A global effect of beta-amyloid on functional connectivity in the frontal, occipital and inferior temporal lobes was observable. Interactive effects of beta-amyloid with gray matter GABA displayed positive PCP connectivity to the frontomedial regions, and the interaction of beta-amyloid with gray matter glutamate indicated positive PCP connectivity to frontal and cerebellar regions. Furthermore, decreased whole-brain but increased fronto-occipital and temporo-parietal dynamic connectivity was found, when GABA interacted with regional beta-amyloid deposits in the amygdala, frontal lobe, hippocampus, insula and striatum. CONCLUSIONS: GABA, and less so glutamate, may moderate beta-amyloid related functional connectivity. Additional research is needed to better characterize their interaction and potential impact on AD.


Assuntos
Envelhecimento/fisiologia , Peptídeos beta-Amiloides/metabolismo , Cerebelo/fisiologia , Córtex Cerebral/fisiologia , Ácido Glutâmico/metabolismo , Substância Cinzenta/fisiologia , Neuroimagem/métodos , Ácido gama-Aminobutírico/metabolismo , Idoso , Envelhecimento/metabolismo , Compostos de Anilina , Cerebelo/diagnóstico por imagem , Cerebelo/metabolismo , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Conectoma/métodos , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/metabolismo , Humanos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Tomografia por Emissão de Pósitrons/métodos , Tiazóis
4.
Neuroimage ; 174: 308-316, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29548847

RESUMO

The accumulation of ß-amyloid plaques is a hallmark of Alzheimer's disease (AD), and recently published data suggest that increased brain iron burden may reflect pathologies that synergistically contribute to the development of cognitive dysfunction. While preclinical disease stages are considered most promising for therapeutic intervention, the link between emerging AD-pathology and earliest clinical symptoms remains largely unclear. In the current study we therefore investigated local correlations between iron and ß-amyloid plaques, and their possible association with cognitive performance in healthy older adults. 116 older adults (mean age 75 ±â€¯7.4 years) received neuropsychological testing to calculate a composite cognitive score of performance in episodic memory, executive functioning, attention, language and communication. All participants were scanned on a combined PET-MRI instrument and were administered T1-sequences for anatomical mapping, quantitative susceptibility mapping (QSM) for assessing iron, and 18F-Flutemetamol-PET for estimating ß-amyloid plaque load. Biological parametric mapping (BPM) was used to generate masks indicating voxels with significant (p < 0.05) correlation between susceptibility and 18F-Flutemetamol-SUVR. We found a bilateral pattern of clusters characterized by a statistical relationship between magnetic susceptibility and 18F-Flutemetamol-SUVR, indicating local correlations between iron and ß-amyloid plaque deposition. For two bilateral clusters, located in the frontal and temporal cortex, significant relationships (p<0.05) between local ß-amyloid and the composite cognitive performance score could be observed. No relationship between whole-cortex ß-amyloid plaque load and cognitive performance was observable. Our data suggest that the local correlation of ß-amyloid plaque load and iron deposition may provide relevant information regarding cognitive performance of healthy older adults. Further studies are needed to clarify pathological correlates of the local interaction of ß-amyloid, iron and other causes of altered magnetic susceptibility.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Cognição , Ferro/metabolismo , Placa Amiloide/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Compostos de Anilina , Benzotiazóis , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons
5.
Eur J Vasc Endovasc Surg ; 54(2): 203-211, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28587797

RESUMO

OBJECTIVE/BACKGROUND: Endovascular first is the preferred therapy approach to critical limb ischaemia (CLI). However, in spite of new endovascular techniques, bypass surgery still plays an important role, especially in patients with complex anatomy in whom endovascular therapy is not considered feasible, or has failed. The goal of this study was to analyse the outcomes of prosthetic or autologous vein for femoropopliteal (P3) bypasses performed under the abovementioned conditions. METHODS: A retrospective analysis of patients who underwent a femoropopliteal (P3) bypass for CLI (March 2007-December 2015) was conducted. Endovascular therapy was not possible. Patency rates, limb salvage, major adverse limb event (MALE) free survival, and survival after 5 years were analysed. RESULTS: In total, 151 cases were included in the analysis (rest pain 35.8%, ulcer/gangrene 64.3%). The graft material was autologous vein in 76 cases (vein group) and heparin bonded expanded polytetrafluoroethylene (HePTFE) in 75 cases (HePTFE group). Indications, risk factors, previous revascularisation procedures, and runoff vessels were similar in both groups. Thirty day mortality was 6.6% in the vein group and 5.3% in the HePTFE group (p = .508), early graft occlusion (6.6% vs. 5.3%; p = .508) and 30 day major amputation rate (0% vs. 2.7%; p = .245) were similar between the two groups. Overall primary patency was 51.7% (55.5% [vein group] vs. 51.7% [HePTFE group]; p = .897) and overall secondary patency was 64.2% (74.6% [vein group] vs. 55.6% [HePTFE group]; p = .119), all without significance after 5 years. However, limb salvage (79.1%) was significantly different (90.0% [vein group] vs. 62.9% [HePTFE group]; p = .021). Survival was similar between the groups (47.3% vs. 42.9%; p = .582) as well as MALE free survival (69.4% vs. 55.0%; p = .348). CONCLUSION: Bypasses to the below knee popliteal artery show good results in patients with CLI unsuitable for endovascular therapy. Vein is still the first line graft material.


Assuntos
Anticoagulantes/administração & dosagem , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Materiais Revestidos Biocompatíveis , Artéria Femoral/cirurgia , Heparina/administração & dosagem , Isquemia/cirurgia , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/cirurgia , Politetrafluoretileno , Artéria Poplítea/cirurgia , Veias/transplante , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica , Anticoagulantes/efeitos adversos , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Estado Terminal , Intervalo Livre de Doença , Feminino , Artéria Femoral/fisiopatologia , Heparina/efeitos adversos , Humanos , Isquemia/diagnóstico , Isquemia/mortalidade , Isquemia/fisiopatologia , Estimativa de Kaplan-Meier , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Artéria Poplítea/fisiopatologia , Modelos de Riscos Proporcionais , Desenho de Prótese , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Transplante Autólogo , Resultado do Tratamento , Grau de Desobstrução Vascular
6.
Australas J Dermatol ; 58(4): e160-e170, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28295176

RESUMO

UV radiation exposure is the major contributor to photocarcinogenesis and photoageing. Reducing UV radiation exposure can be achieved by using adequate sunscreen preparations. The use of sunscreen can significantly reduce the incidence of squamous cell carcinoma, actinic keratoses and invasive melanoma. In the Australian market over 900 sunscreen products are available, each with their own brand, formulation and ingredients. It can be difficult for dermatologists and consumers to determine which are the most effective and appropriate products to use. We discuss the specific active ingredients found in sunscreen formulations available in Australia, their mode of protection, photostability, solubility, and side-effects and the methods used by the Therapeutic Goods Administration to determine the ratings and efficacy of each sunscreen.


Assuntos
Compostos Inorgânicos/farmacologia , Compostos Orgânicos/farmacologia , Fator de Proteção Solar , Protetores Solares/química , Protetores Solares/farmacologia , Animais , Austrália , Dermatite de Contato/etiologia , Sistema Endócrino/efeitos dos fármacos , Humanos , Compostos Inorgânicos/efeitos adversos , Nanopartículas/efeitos adversos , Compostos Orgânicos/efeitos adversos , Veículos Farmacêuticos , Protetores Solares/efeitos adversos , Protetores Solares/normas
8.
Surgeon ; 15(2): 69-75, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26164740

RESUMO

OBJECTIVE: In this study we analyzed the outcome of tibial and peroneal venous and heparin-bonded expanded polytetrafluoroethylene (HePTFE) bypasses in diabetics with critical limb ischemia (CLI). We aimed to verify our hypothesis that HePTFE grafts will achieve acceptable 1-year patency and limb salvage results in patients who lack an adequate vein. METHODS: We conducted a retrospective analysis for all diabetics who underwent tibial bypass surgery in our department between October 2007 and October 2012. The study includes 97 grafts. All these patients were not suited for an endovascular therapy. We used autologous veins in 56 cases (Vein-Group) and HePTFE grafts in 41 cases (HePTFE-Group). Study endpoints were primary and secondary patency, limb salvage, and survival at 2 years postoperatively. RESULTS: Risk factors and indications were similar in both groups. The comparison between HePTFE- and Vein-Group showed significantly different patency rates. At 2 years, primary patency was 39.3% in HePTFE-Group vs. 78.5% in Vein-Group (P = .003) and secondary patency was 47.4% vs. 81.9% (P = .002). Limb salvage at 2 years was 79.3% vs. 87.4% (P = .073) and survival was 64.6% vs. 62.9% (P = .593) at the 2-year mark, with no significant differences. 30-days mortality, graft occlusion and major amputation rate showed no significant differences, either. CONCLUSIONS: This study shows that HePTFE bypasses are a viable option for diabetics undergoing tibial bypass surgery when no adequate vein is available.


Assuntos
Anticoagulantes/uso terapêutico , Prótese Vascular , Angiopatias Diabéticas/cirurgia , Heparina/uso terapêutico , Extremidade Inferior/irrigação sanguínea , Politetrafluoretileno , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
9.
Sci Rep ; 6: 35514, 2016 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-27748454

RESUMO

Quantitative Susceptibility Mapping (QSM) MRI at 7 Tesla and 11-Carbon Pittsburgh-Compound-B PET were used for investigating the relationship between brain iron and Amyloid beta (Aß) plaque-load in a context of increased risk for Alzheimer's disease (AD), as reflected by the Apolipoprotein E ε4 (APOE-e4) allele and mild cognitive impairment (MCI) in elderly subjects. Carriers of APOE-e4 with normal cognition had higher cortical Aß-plaque-load than non-carriers. In MCI an association between APOE-e4 and higher Aß-plaque-load was observable both for cortical and subcortical brain-regions. APOE-e4 and MCI was also associated with higher cortical iron. Moreover, cerebral iron significantly affected functional coupling, and was furthermore associated with increased Aß-plaque-load (R2-adjusted = 0.80, p < 0.001) and APOE-e4 carrier status (p < 0.001) in MCI. This study confirms earlier reports on an association between increased brain iron-burden and risk for neurocognitive dysfunction due to AD, and indicates that disease-progression is conferred by spatial colocalization of brain iron deposits with Aß-plaques.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Disfunção Cognitiva/metabolismo , Ferro/metabolismo , Idoso , Idoso de 80 Anos ou mais , Apolipoproteína E4/genética , Encéfalo/patologia , Estudos de Casos e Controles , Disfunção Cognitiva/diagnóstico por imagem , Demografia , Feminino , Heterozigoto , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Tomografia por Emissão de Pósitrons , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/patologia
10.
Biomedicines ; 4(3)2016 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-28536387

RESUMO

Pancreatic cancer is an aggressive disease with a five year survival rate of less than 5%, which is associated with late presentation. In recent years, research into nanomedicine and the use of nanoparticles as therapeutic agents for cancers has increased. This article describes the latest developments in the use of nanoparticles, and evaluates the risks and benefits of nanoparticles as an emerging therapy for pancreatic cancer. The Preferred Reporting Items of Systematic Reviews and Meta-Analyses checklist was used. Studies were extracted by searching the Embase, MEDLINE, SCOPUS, Web of Science, and Cochrane Library databases from inception to 18 March 2016 with no language restrictions. Clinical trials involving the use of nanoparticles as a therapeutic or prognostic option in patients with pancreatic cancer were considered. Selected studies were evaluated using the Jadad score for randomised control trials and the Therapy CA Worksheet for intervention studies. Of the 210 articles found, 10 clinical trials including one randomised control trial and nine phase I/II clinical trials met the inclusion criteria and were analysed. These studies demonstrated that nanoparticles can be used in conjunction with chemotherapeutic agents increasing their efficacy whilst reducing their toxicity. Increased efficacy of treatment with nanoparticles may improve the clinical outcomes and quality of life in patients with pancreatic cancer, although the long-term side effects are yet to be defined. The study registration number is CRD42015020009.

11.
Gene Ther ; 22(8): 628-35, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25871827

RESUMO

The leishmaniases are a complex of vector-borne diseases caused by protozoan parasites of the genus Leishmania. LEISHDNAVAX is a multi-antigen, T-cell epitope-enriched DNA vaccine candidate against human leishmaniasis. The vaccine candidate has been proven immunogenic and showed prophylactic efficacy in preclinical studies. Here, we describe the safety testing of LEISHDNAVAX in naive mice and rats, complemented by the demonstration of tolerability in Leishmania-infected mice. Biodistribution and persistence were examined following single and repeated intradermal (i.d.) administration to rats. DNA vectors were distributed systemically but did not accumulate upon repeated injections. Although vector DNA was cleared from most other tissues within 60 days after the last injection, it persisted in skin at the site of injection and in draining lymph nodes. Evaluation of single-dose and repeated-dose toxicity of the vaccine candidate after i.d. administration to naive, non-infected mice did not reveal any safety concerns. LEISHDNAVAX was also well tolerated in Leishmania-infected mice. Taken together, our results substantiate a favorable safety profile of LEISHDNAVAX in both naive and infected animals and thus, support the initiation of clinical trials for both preventive and therapeutic applications of the vaccine.


Assuntos
Leishmaniose/imunologia , Vacinas de DNA/efeitos adversos , Animais , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Vetores Genéticos , Leishmaniose/prevenção & controle , Camundongos Endogâmicos BALB C , Ratos Wistar , Vacinas de DNA/administração & dosagem , Vacinas de DNA/uso terapêutico
12.
Int J Surg ; 13: 261-266, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25528633

RESUMO

BACKGROUND: Endovascular recanalization has become the accepted first-line treatment strategy for most lower extremity arterial occlusions, especially in patients with critical limb ischemia (Rutherford 4-6). Prior endovascular interventions have been described as risk factors for the outcome of subsequent lower extremity bypass surgery. The effect on subsequent tibial and peroneal bypasses is controversial. We analyzed the impact of prior endovascular lower extremity revascularization procedures on the short- and mid-term results of femoro-tibial and femoro-peroneal bypasses. METHODS: A retrospective analysis was conducted of all patients who had undergone tibial or peroneal bypass surgery after prior endovascular interventions (PEI-Group, n=40) of the same extremity in our department from October 2007 to October 2012. We compared this group with a group of patients who had received a tibial or peroneal bypass as primary revascularization procedure (BF-Group, n=93) during the same period of time because primary endovascular therapy had been deemed unfeasible in those cases. Indication in all cases was critical limb ischemia; the median age was 78 years (range 50-90 years), 45.1% were diabetics, and 42.9% were female. The graft material was autologous vein in 80 cases and HePTFE in 53 cases. Endpoints of the analysis were primary and secondary patency rates, limb salvage and survival at 2 years postoperatively. RESULTS: At 2 years overall primary patency was 68.4%, secondary patency was 69.5%, limb salvage was 83.6% and survival was 62.6%. Primary patency for the BF-Group was 74.3% vs. 55.1% for the PEI-Group (P=.310) at 2 years; secondary patency was 74.6% vs. 59.1% (P=.268). Prior endovascular intervention did not have any significant effects on limb salvage (83.7% vs. 83.6%; P=.470) or survival rates (61.0% vs. 65.0%; P=.258) at the 2-year mark, either. There were no significant differences in graft occlusion, death and major amputation rates within the first 30 postoperative days. Except for male gender, there were no significant differences in risk factors and indications between the two groups. CONCLUSIONS: Prior endovascular intervention of femoro-tibial vessels does not have a negative impact on the outcome of subsequent tibial or peroneal bypass surgery in patients with critical limb ischemia.


Assuntos
Arteriopatias Oclusivas/cirurgia , Procedimentos Endovasculares/métodos , Isquemia/cirurgia , Extremidade Inferior/irrigação sanguínea , Enxerto Vascular/métodos , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica , Estudos de Coortes , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Salvamento de Membro/métodos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento , Enxerto Vascular/efeitos adversos , Grau de Desobstrução Vascular
13.
Mol Psychiatry ; 18(3): 358-68, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22688190

RESUMO

Serum antibodies against amyloid-ß peptide (Aß) in humans with or without diagnosis of Alzheimer's disease (AD) indicate the possibility of immune responses against brain antigens. In an unbiased screening for antibodies directed against brain proteins, we found in AD patients high serum levels of antibodies against the neuronal cytoskeletal protein ankyrin G (ankG); these correlated with slower rates of cognitive decline. Neuronal expression of ankG was higher in AD brains than in nondemented age-matched healthy control subjects. AnkG was present in exosomal vesicles, and it accumulated in ß-amyloid plaques. Active immunization with ankG of arcAß transgenic mice reduced brain ß-amyloid pathology and increased brain levels of soluble Aß(42). AnkG immunization induced a reduction in ß-amyloid pathology, also in Swedish transgenic mice(.) Anti-ankG monoclonal antibodies reduced Aß-induced loss of dendritic spines in hippocampal ArcAß organotypic cultures. Together, these data established a role for ankG in the human adaptive immune response against resident brain proteins, and they show that ankG immunization reduces brain ß-amyloid and its related neuropathology.


Assuntos
Doença de Alzheimer/imunologia , Doença de Alzheimer/prevenção & controle , Anquirinas/imunologia , Encéfalo/patologia , Vacinação , Doença de Alzheimer/sangue , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/toxicidade , Animais , Anquirinas/metabolismo , Anticorpos/sangue , Anticorpos Monoclonais/farmacologia , Encéfalo/metabolismo , Células Cultivadas , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Humanos , Camundongos , Camundongos Transgênicos , Neurônios/citologia , Fragmentos de Peptídeos/metabolismo , Placa Amiloide/metabolismo
14.
Transl Psychiatry ; 2: e183, 2012 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-23149447

RESUMO

Pathogenic amyloid-ß peptide precursor (APP) mutations clustered around position 693 of APP-position 22 of the Aß sequence--are commonly associated with congophilic amyloid angiopathy (CAA) and intracerebral hemorrhages. In contrast, the Osaka (E693Δ) intra-Aß APP mutation shows a recessive pattern of inheritance that leads to AD-like dementia despite low brain amyloid on in vivo positron emission tomography imaging. Here, we investigated the effects of the Osaka APP mutation on Aß accumulation and deposition in vivo using a newly generated APP transgenic mouse model (E22ΔAß) expressing the Osaka mutation together with the Swedish (K670N/M671L) double mutation. E22ΔAß mice exhibited reduced α-processing of APP and early accumulation of intraneuronal fibrillar Aß oligomers associated with cognitive deficits. In line with our in vitro findings that recombinant E22Δ-mutated Aß peptides form amyloid fibrils, aged E22ΔAß mice showed extracellular CAA deposits in leptomeningeal cerebellar and cortical vessels. In vitro results from thioflavin T aggregation assays with recombinant Aß peptides revealed a yet unknown antiamyloidogenic property of the E693Δ mutation in the heterozygous state and an inhibitory effect of E22Δ Aß42 on E22Δ Aß40 fibrillogenesis. Moreover, E22Δ Aß42 showed a unique aggregation kinetics lacking exponential fibril growth and poor seeding effects on wild-type Aß aggregation. These results provide a possible explanation for the recessive trait of inheritance of the Osaka APP mutation and the apparent lack of amyloid deposition in E693Δ mutation carriers.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Encéfalo , Placa Amiloide , Fatores Etários , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Comportamento Animal , Encéfalo/metabolismo , Encéfalo/patologia , Angiopatia Amiloide Cerebral/genética , Angiopatia Amiloide Cerebral/metabolismo , Modelos Animais de Doenças , Camundongos , Camundongos Transgênicos , Mutação , Placa Amiloide/metabolismo , Placa Amiloide/patologia
15.
Dement Geriatr Cogn Disord ; 33(6): 416-22, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22814208

RESUMO

BACKGROUND: Early diagnosis of Alzheimer's disease (AD) may be corroborated by imaging of beta-amyloid plaques using positron emission tomography (PET). Here, we performed an add-on questionnaire study to evaluate the relevance of florbetaben imaging (BAY 949172) in diagnosis and consecutive management of probable AD patients. METHODS: AD patients with a clinical diagnosis in accordance with the NINCDS-ADRDA criteria or controls were imaged using florbetaben. Referring physicians were asked on a voluntary basis about their confidence in initial diagnosis, significance of PET imaging results, and their anticipated consequences for future patient care. RESULTS: 121 questionnaires for probable AD patients and 80 questionnaires for controls were evaluated. In 18% of patients who had initially received the diagnosis of probable AD, PET scans were rated negative, whereas in controls 18% of scans were positive. An increase in confidence in the initial diagnosis was frequently reported (80%). Imaging results had a significant impact on the intended patient care, as judged by the referring physicians; this was most prominent in those patients with a contradicting scan and/or a low confidence in the initial diagnosis. CONCLUSION: Florbetaben amyloid imaging increases the overall confidence in diagnosis of AD and may frequently influence clinical decisions and patient management.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Padrões de Prática Médica , Idoso , Idoso de 80 Anos ou mais , Peptídeos beta-Amiloides/metabolismo , Compostos de Anilina , Encéfalo/diagnóstico por imagem , Tomada de Decisões , Diagnóstico Precoce , Feminino , Humanos , Masculino , Planejamento de Assistência ao Paciente , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Estilbenos
16.
Opt Express ; 20(11): 12610-21, 2012 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-22714248

RESUMO

We have rationally designed two-dimensional Au and Ag hole arrays for high performing surface plasmon resonance (SPR) sensing. The figure-of-merit (FOM), which is defined as sensitivity/linewidth, is found to be highly geometry-dependent. For sensitivity, we find it is equal to the period of array when exciting low order surface plasmon modes at low incident angle. Therefore, increasing period improves sensitivity. On the other hand, narrow linewidth can be obtained from small hole size so that the radiative decay loss is minimized. By using a pair of orthogonally oriented polarizer and analyzer, the signal-to-noise ratio (SNR) can be greatly enhanced due to the elimination of the nonresonant reflection background. As a proof of our strategy, we have obtained FOM larger than 100/RIU and SNR higher than 110 from Au arrays. Our results show the importance of understanding the basic properties of surface plasmon polaritons in order to systematically optimize the performance of the plasmonic system for a given application.


Assuntos
Desenho Assistido por Computador , Metais/química , Modelos Teóricos , Refratometria/instrumentação , Ressonância de Plasmônio de Superfície/instrumentação , Transdutores , Simulação por Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Luz , Espalhamento de Radiação
17.
Nanotoxicology ; 6: 847-56, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22022996

RESUMO

Gold nanorods (Au-NRs) have attracted enormous interest due to their size and unique optical properties. Many studies have demonstrated their use in biomedical systems. However, their potential toxicity is not fully understood. This study evaluated the effects of the Au-NRs (15 nM × 64 nM) coated with CTAB (cetyltrimethylammonium bromide) or PEG (polyethylene glycol) in human erythrocytes on the induction of haemolysis and erythroptosis. In our study, erythroptosis (also known as eryptosis) was determined systematically through the measurement of feature events of apoptosis by flow cytometry. We found that the CTAB- and PEG-coated Au-NRs up to 0.5 nM did not cause severe haemolysis. However, the CTAB-Au-NRs were more toxic than the PEG-Au-NRs. The toxicity of the CTAB-Au-NRs was largely due to the CTAB residues from desorption or incomplete purification. Mechanistically, cytosolic Ca(2+) ions seem to be the key mediator in the eryptosis/erythroptosis mediated by the CTAB or CTAB-Au-NRs while caspase-3 and reactive oxygen species did not contribute much to the process.


Assuntos
Apoptose/efeitos dos fármacos , Compostos de Cetrimônio/toxicidade , Eritrócitos/efeitos dos fármacos , Ouro/química , Nanotubos/toxicidade , Polietilenoglicóis/toxicidade , Caspase 3/metabolismo , Cetrimônio , Eritrócitos/enzimologia , Hemólise/efeitos dos fármacos , Humanos , Técnicas In Vitro , Estresse Oxidativo/efeitos dos fármacos
18.
Meat Sci ; 88(3): 531-4, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21388752

RESUMO

In a retrospective study on the microbiology of minced meat from small food businesses supplying directly to the consumer, the relative contribution of meat supplier, meat species and outlet where meat was minced was assessed by "Classification and Regression Tree" (CART) analysis. Samples (n=888) originated from 129 outlets of a single supermarket chain. Sampling units were 4-5 packs (pork, beef, and mixed pork-beef). Total aerobic counts (TACs) were 5.3±1.0 log CFU/g. In 75.6% of samples, E. coli were <1 log CFU/g. The proportion of "unsatisfactory" sample sets [as defined in Reg. (EC) 2073/2005] were 31.3 and 4.5% for TAC and E. coli, respectively. For classification according to TACs, the outlet where meat was minced and the "meat supplier" were the most important predictors. For E. coli, "outlet" was the most important predictor, but the limit of detection of 1 log CFU/g was not discriminative enough to allow further conclusions.


Assuntos
Técnicas de Tipagem Bacteriana , Bactérias Aeróbias Gram-Negativas/classificação , Produtos da Carne/classificação , Produtos da Carne/microbiologia , Modelos Estatísticos , Animais , Bovinos , Contagem de Colônia Microbiana , Escherichia coli/classificação , Escherichia coli/isolamento & purificação , União Europeia , Manipulação de Alimentos/métodos , Inspeção de Alimentos/legislação & jurisprudência , Abastecimento de Alimentos/economia , Doenças Transmitidas por Alimentos/prevenção & controle , Bactérias Aeróbias Gram-Negativas/isolamento & purificação , Produtos da Carne/economia , Produtos da Carne/normas , Indústria de Embalagem de Carne , Análise de Regressão , Estudos Retrospectivos , Empresa de Pequeno Porte/legislação & jurisprudência , Sus scrofa
19.
ACS Nano ; 4(1): 432-8, 2010 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-20028101

RESUMO

We study surface plasmon polariton lifetimes in two-dimensional arrays of blind holes on gold surfaces. The lifetimes are determined from the line widths of the resonant dips appearing in the specular reflection spectra. We find a strong dependence of lifetimes on the resonant wavelength and the hole geometry. Through both experiments and numerical simulations, we analyze the validity of the Rayleigh approximation and also explore the range of wavelengths and geometric parameters where it fails. Finally, we show that, within the range of geometries and wavelengths considered in our experiments, the behavior of surface plasmon polariton lifetimes can be understood as resulting from the interplay between the intrinsic metal absorption and the scattering of surface waves by single isolated holes.

20.
Phys Rev Lett ; 103(7): 073401, 2009 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-19792643

RESUMO

We present an experimental study of the thermodynamics of free, size-selected water cluster anions consisting of 48 and 118 molecules. The measured caloric curves of the clusters are bulklike at low temperatures but show a well-defined, particle-size specific transition at 93+/-3 K for (H2O)48- and 118+/-3 K for (H2O)118-. At the transition temperature the heat capacity strongly increases, which marks the onset of melting.

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