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1.
Nanoscale ; 16(19): 9625, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38699844

RESUMO

Correction for 'Magnetic aerogels from FePt and CoPt3 directly from organic solution' by L. Schoske et al., Nanoscale, 2024, 16, 4229-4238, https://doi.org/10.1039/D3NR05892A.

2.
Nanoscale ; 16(8): 4229-4238, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38345355

RESUMO

Here the synthesis of magnetic aerogels from iron platinum and cobalt platinum nanoparticles is presented. The use of hydrazine monohydrate as destabilizing agent triggers the gelation directly from organic solution, and therefore a phase transfer to aqueous media prior to the gelation is not necessary. The aerogels were characterized through Transmission Electron Microscopy, Scanning Electron Microscopy, Powder X-Ray Diffraction Analysis and Argon Physisorption measurements to prove the formation of a porous network and define their compositions. Additionally, magnetization measurements in terms of hysteresis cycles at 5 K and 300 K (M-H-curves) as well as zero field cooled-field cooled measurements (ZFC-FC measurements) of the dried colloids and the respective xero- and aerogels were performed, in order to analyze the influence of the gelation process and the network structure on the magnetic properties.

3.
Ann Oncol ; 34(1): 111-120, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36208697

RESUMO

BACKGROUND: Genomic analysis of circulating tumor DNA (ctDNA) is increasingly incorporated into the clinical management of patients with advanced cancer. Beyond tumor profiling, ctDNA analysis also can enable calculation of circulating tumor fraction (TF), which has previously been found to be prognostic. While most prognostic models in metastatic cancer are tumor type specific and require significant patient-level data, quantification of TF in ctDNA has the potential to serve as a pragmatic, tumor-agnostic prognostic tool. PATIENTS AND METHODS: This study utilized a cohort of patients in a nationwide de-identified clinico-genomic database with metastatic castration-resistant prostate cancer (mCRPC), metastatic breast cancer (mBC), advanced non-small-cell lung cancer (aNSCLC), or metastatic colorectal cancer (mCRC) undergoing liquid biopsy testing as part of routine care. TF was calculated based on single-nucleotide polymorphism aneuploidy across the genome. Clinical, disease, laboratory, and treatment data were captured from the electronic health record. Overall survival (OS) was evaluated by TF level while controlling for relevant covariables. RESULTS: A total of 1725 patients were included: 198 mCRPC, 402 mBC, 902 aNSCLC, and 223 mCRC. TF ≥10% was highly correlated with OS in univariable analyses for all cancer types: mCRPC [hazard ratio (HR) 3.3, 95% confidence interval (CI) 2.04-5.34, P < 0.001], mBC (HR 2.4, 95% CI 1.71-3.37, P < 0.001), aNSCLC (HR 1.68, 95% CI 1.34-2.1, P < 0.001), and mCRC (HR 2.11, 95% CI 1.39-3.2, P < 0.001). Multivariable assessments of TF had similar point estimates and CIs, suggesting a consistent and independent association with survival. Exploratory analysis showed that TF remained consistently prognostic across a wide range of cutpoints. CONCLUSIONS: Plasma ctDNA TF is a pragmatic, independent prognostic biomarker across four advanced cancers with potential to guide clinical conversations around expected treatment outcomes. With further prospective validation, ctDNA TF could be incorporated into care paradigms to enable precision escalation and de-escalation of cancer therapy based on patient-level tumor biology.


Assuntos
Neoplasias da Mama , Carcinoma Pulmonar de Células não Pequenas , DNA Tumoral Circulante , Neoplasias Pulmonares , Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , Biomarcadores Tumorais , Prognóstico , Neoplasias de Próstata Resistentes à Castração/terapia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Feminino
4.
Polymers (Basel) ; 13(12)2021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34199206

RESUMO

The macromolecular dynamics of dendronized copolymer membranes (PECHs), obtained by chemical modification of poly(epichlorohydrin) with the dendron 3,4,5-tris[4-(n-dodecan-1-yloxy)benzyloxy] benzoate, was investigated. In response to a thermal treatment during membrane preparation, these copolymers show an ability to change their shape, achieve orientation, and slightly crystallize, which was also observed by CP-MAS NMR, XRD, and DSC. The phenomenon was deeply analyzed by dielectric thermal analysis. The dielectric spectra show the influence of several factors such as the number of dendritic side groups, the orientation, their self-assembling dendrons, and the molecular mobility. The dielectric spectra present a sub-Tg dielectric relaxation, labelled as γ, associated with the mobility of the benzyloxy substituent of the dendritic group. This mobility is not related to the percentage of these lateral chains but is somewhat hindered by the orientation of the dendritic groups. Unlike other less complex polymers, the crystallization was dismantled before the appearance of the glass transition (αTg). Only after that, clearing transition (αClear) can be observed. The PECHs were flexible and offered a high free volume, despite presenting a high degree of modifications. However, the molecular mobility is not independent in each phase and the self-assembling dendrons can be eventually fine-tuned according to the percentage of grafted groups.

5.
J Comp Pathol ; 163: 1-5, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30213367

RESUMO

Feline injection site sarcomas (FISS) were first described in the early 1990s. Despite extensive research, the pathogenesis of these tumours has not been elucidated conclusively. Their appearance and the marked increase in their incidence has been mainly connected to the injection of vaccines, and it is assumed that a chronic inflammatory reaction at the injection site triggers subsequent malignant transformation. The role of alum-based adjuvants has been discussed, but is controversial. The present study of the Swiss Feline Cancer Registry (SFCR) with data from 2009 to 2014 revealed a marked decrease of the incidence of fibrosarcomas compared with the previous observation period. Notably, this drop occurred after a non-adjuvanted feline leukaemia virus vaccine was introduced in Switzerland in 2007. This observation, together with the previous findings of the SFCR, further supports the notion that alum-adjuvanted vaccines are involved in the genesis of FISS and that non-adjuvanted vaccines might be safer for cats.


Assuntos
Doenças do Gato/patologia , Reação no Local da Injeção/veterinária , Sarcoma/veterinária , Neoplasias de Tecidos Moles/veterinária , Animais , Gatos , Reação no Local da Injeção/patologia , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Suíça
6.
Am J Physiol Gastrointest Liver Physiol ; 314(4): G517-G536, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29167114

RESUMO

Glutamine (Gln) is the most concentrated amino acid in blood and considered conditionally essential. Its requirement is increased during physiological stress, such as malnutrition or illness, despite its production by muscle and other organs. In the malnourished state, Gln has been suggested to have a trophic effect on the exocrine pancreas and small intestine. However, the Gln transport capacity, the functional relationship of these two organs, and the potential role of the Gln-glutamate (Glu) cycle are unknown. We observed that pancreatic acinar cells express lower levels of Glu than Gln transporters. Consistent with this expression pattern, the rate of Glu influx into acinar cells was approximately sixfold lower than that of Gln. During protein restriction, acinar cell glutaminase expression was increased and Gln accumulation was maintained. Moreover, Glu secretion by acinar cells into pancreatic juice and thus into the lumen of the small intestine was maintained. In the intestinal lumen, Glu absorption was preserved and Glu dehydrogenase expression was augmented, potentially providing the substrates for increasing energy production via the TCA cycle. Our findings suggest that one mechanism by which Gln exerts a positive effect on exocrine pancreas and small intestine involves the Gln metabolism in acinar cells and the secretion of Glu into the small intestine lumen. The exocrine pancreas acinar cells not only avidly accumulate Gln but metabolize Gln to generate energy and to synthesize Glu for secretion in the pancreatic juice. Secreted Glu is suggested to play an important role during malnourishment in sustaining small intestinal homeostasis. NEW & NOTEWORTHY Glutamine (Gln) has been suggested to have a trophic effect on exocrine pancreas and small intestine in malnourished states, but the mechanism is unknown. In this study, we suggest that this trophic effect derives from an interorgan relationship between exocrine pancreas and small intestine for Gln-glutamate (Glu) utilization involving the uptake and metabolism of Gln in acinar cells and secretion of Glu into the lumen of the small intestine.


Assuntos
Células Acinares/metabolismo , Enterócitos/metabolismo , Glutamina , Intestino Delgado , Desnutrição/metabolismo , Pâncreas Exócrino , Animais , Transporte Biológico/fisiologia , Dieta com Restrição de Proteínas , Glutamato Desidrogenase/metabolismo , Glutamina/sangue , Glutamina/metabolismo , Intestino Delgado/metabolismo , Intestino Delgado/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Pâncreas Exócrino/metabolismo , Pâncreas Exócrino/fisiopatologia , Suco Pancreático/metabolismo , Ratos , Ratos Wistar
7.
Heredity (Edinb) ; 118(2): 193-201, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27703154

RESUMO

Numerous landscape genomic studies have identified single-nucleotide polymorphisms (SNPs) and genes potentially involved in local adaptation. Rarely, it has been explicitly evaluated whether these environmental associations also hold true beyond the populations studied. We tested whether putatively adaptive SNPs in Arabidopsis halleri (Brassicaceae), characterized in a previous study investigating local adaptation to a highly heterogeneous environment, show the same environmental associations in an independent, geographically enlarged set of 18 populations. We analysed new SNP data of 444 plants with the same methodology (partial Mantel tests, PMTs) as in the original study and additionally with a latent factor mixed model (LFMM) approach. Of the 74 candidate SNPs, 41% (PMTs) and 51% (LFMM) were associated with environmental factors in the independent data set. However, only 5% (PMTs) and 15% (LFMM) of the associations showed the same environment-allele relationships as in the original study. In total, we found 11 genes (31%) containing the same association in the original and independent data set. These can be considered prime candidate genes for environmental adaptation at a broader geographical scale. Our results suggest that selection pressures in highly heterogeneous alpine environments vary locally and signatures of selection are likely to be population-specific. Thus, genotype-by-environment interactions underlying adaptation are more heterogeneous and complex than is often assumed, which might represent a problem when testing for adaptation at specific loci.


Assuntos
Adaptação Fisiológica/genética , Arabidopsis/genética , Clima , Interação Gene-Ambiente , Polimorfismo de Nucleotídeo Único , Alelos , Genes de Plantas , Genética Populacional , Genótipo , Geografia , Modelos Lineares , Modelos Genéticos , Seleção Genética
8.
J Comp Pathol ; 155(2-3): 156-170, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27406312

RESUMO

This study is based on the Swiss Canine Cancer Registry, comprising 121,963 diagnostic records of dogs compiled between 1955 and 2008, in which 63,214 (51.83%) animals were diagnosed with tumour lesions through microscopical investigation. Adenoma/adenocarcinoma (n = 12,293, 18.09%) was the most frequent tumour diagnosis. Other common tumour diagnoses were: mast cell tumour (n = 4,415, 6.50%), lymphoma (n = 2,955, 4.35%), melanocytic tumours (n = 2,466, 3.63%), fibroma/fibrosarcoma (n = 2,309, 3.40%), haemangioma/haemangiosarcoma (n = 1,904, 2.80%), squamous cell carcinoma (n = 1,324, 1.95%) and osteoma/osteosarcoma (n = 842, 1.24%). The relative occurrence over time and the most common body locations of those tumour diagnoses are presented. Analyses of the influence of age, breed, body size, sex and neutering status on tumour development were carried out using multiple logistic regression. In certain breeds/breed categories the odds ratios (ORs) for particular tumours were outstandingly high: the boxer had higher ORs for mast cell tumour and haemangioma/haemangiosarcoma, as did the shepherd group for haemangioma/haemangiosarcoma, the schnauzer for squamous cell carcinoma and the rottweiler for osteoma/osteosarcoma. In small dogs, the risk of developing mammary tumours was three times higher than in large dogs. However, small dogs were less likely to be affected by many other tumour types (e.g. tumours of the skeletal system). Examination of the influence of sex and neutering status on tumour prevalence showed that the results depend on the examination method. In all sampling groups the risk for female dogs of developing adenoma/adenocarcinoma was higher than for male dogs. Females had a lower risk of developing haemangioma/haemangiosarcoma and squamous cell carcinoma than males. Neutered animals were at higher risk of developing specific tumours outside the genital organs than intact animals. The sample size allows detailed insight into the influences of age, breed, body size, sex and neutering status on canine tumour development. In many cases, the analysis confirms the findings of other authors. In some cases, the results are unique or contradict other studies, implying that further investigations are necessary.


Assuntos
Doenças do Cão/epidemiologia , Doenças do Cão/patologia , Neoplasias/veterinária , Sistema de Registros , Animais , Cães , Feminino , Masculino
9.
J Comp Pathol ; 154(2-3): 195-210, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26922257

RESUMO

Cancer registries are valuable sources for epidemiological research investigating risk factors underlying different types of cancer incidence. The present study is based on the Swiss Feline Cancer Registry that comprises 51,322 feline patient records, compiled between 1965 and 2008. In these records, 18,375 tumours were reported. The study analyses the influence of sex, neutering status, breed, time and age on the development of the most common tumour types and on their locations, using a multiple logistic regression model. The largest differences between breeds were found in the development of fibrosarcomas and squamous cell carcinomas, as well as in the development of tumours in the skin/subcutis and mammary gland. Differences, although often small, in sex and neutering status were observed in most analyses. Tumours were more frequent in middle-aged and older cats. The sample size allowed detailed analyses of the influence of sex, neutering status, breed and age. Results of the study are mainly consistent with previous analyses; however, some results cannot be compared with the existing literature. Further investigations are necessary, since feline tumours have not been investigated in depth to date. More accurate comparisons would require the definition of international standards for animal cancer registries.


Assuntos
Doenças do Gato/epidemiologia , Fatores Etários , Animais , Gatos , Feminino , Incidência , Masculino , Sistema de Registros , Fatores de Risco , Fatores Sexuais
10.
J Comp Pathol ; 153(4): 266-77, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26422414

RESUMO

Cancer is one of the leading causes of death in companion animals. Information on the epidemiology of cancer is instrumental for veterinary practitioners in patient management; however, spontaneously arising tumours in companion animals also resemble those in man and can provide useful data in combating cancer. Veterinary cancer registries for cats are few in number and have often remained short-lived. This paper presents a retrospective study of tumours in cats in Switzerland from 1965 to 2008. Tumour diagnoses were coded according to topographical and morphological keys of the International Classification of Oncology for Humans (ICD-O-3). Correlations between breed, sex and age were then examined using a multiple logistic regression model. A total of 18,375 tumours were diagnosed in 51,322 cats. Of these, 14,759 (80.3%) tumours were malignant. Several breeds had significantly lower odds ratios for developing a tumour compared with European shorthair cats. The odds of a cat developing a tumour increased with age, up to the age of 16 years, and female cats had higher risk of developing a tumour compared with male cats. Skin (4,970; 27.05%) was the most frequent location for tumours, followed by connective tissue (3,498; 19.04%), unknown location (2,532; 13.78%) and female sexual organs (1,564; 8.51%). The most common tumour types were epithelial tumours (7,913; 43.06%), mesenchymal tumours (5,142; 27.98%) and lymphoid tumours (3,911; 21.28%).


Assuntos
Doenças do Gato/epidemiologia , Neoplasias/veterinária , Sistema de Registros , Animais , Gatos , Neoplasias/epidemiologia , Estudos Retrospectivos , Suíça
11.
J Nanobiotechnology ; 13: 49, 2015 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-26253109

RESUMO

Recent studies report promising results regarding extracorporeal magnetic separation-based blood purification for the rapid and selective removal of disease-causing compounds from whole blood. High molecular weight compounds, bacteria and cells can be eliminated from blood within minutes, hence offering novel treatment strategies for the management of intoxications and blood stream infections. However, risks associated with incomplete particle separation and the biological consequences of particles entering circulation remain largely unclear. This article discusses the promising future of magnetic separation-based purification while keeping important safety considerations in mind.


Assuntos
Segurança do Sangue/métodos , Patógenos Transmitidos pelo Sangue/isolamento & purificação , Circulação Extracorpórea/métodos , Magnetismo/métodos , Nanopartículas de Magnetita/química , Animais , Humanos , Interleucinas/sangue , Interleucinas/isolamento & purificação , Preparações Farmacêuticas/sangue , Preparações Farmacêuticas/isolamento & purificação , Toxinas Biológicas/sangue , Toxinas Biológicas/isolamento & purificação
12.
J Comp Pathol ; 152(2-3): 161-71, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25824119

RESUMO

Diagnostic records are a key feature of any cancer epidemiology, prevention or control strategy for man and animals. Therefore, the information stored in human and animal cancer registries is essential for undertaking comparative epidemiological, pathogenic and therapeutic research. This study presents the Swiss Canine Cancer Registry, containing case data compiled between 1955 and 2008. The data consist of pathology diagnostic records issued by three veterinary diagnostic laboratories in Switzerland. The tumours were classified according to the guidelines of the International Classification of Oncology for Humans on the basis of tumour type, malignancy and body location. The dogs were classified according to breed, age, sex, neuter status and place of residence. The diagnostic data were correlated with data on the Swiss general dog population and the incidence of cancer in dogs was thus investigated. A total of 67,943 tumours were diagnosed in 121,963 dogs and 47.07% of these were malignant. The most common tumour location was the skin (37.05%), followed by mammary glands (23.55%) and soft tissue (13.66%). The most common tumour diagnoses were epithelial (38.45%), mesenchymal (35.10%) and lymphoid tumours (13.23%). The results are compared with data in other canine registries and similarities in tumour distribution and incidence are noted. It is hoped that this study will mark the beginning of continuous registration of dog tumours in Switzerland, which, in turn, will serve as a reference for research in the fields of animal and human oncology.


Assuntos
Doenças do Cão/epidemiologia , Neoplasias/veterinária , Sistema de Registros , Animais , Cães , Neoplasias/epidemiologia , Estudos Retrospectivos , Suíça/epidemiologia
13.
Neuroscience ; 292: 71-80, 2015 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-25701708

RESUMO

BACKGROUND AND PURPOSE: In vivo imaging of inflammatory processes is a valuable tool in stroke research. We here investigated the combination of two imaging modalities in the chronic phase after cerebral ischemia: magnetic resonance imaging (MRI) using intravenously applied ultra small supraparamagnetic iron oxide particles (USPIO), and positron emission tomography (PET) with the tracer [(11)C]PK11195. METHODS: Rats were subjected to permanent middle cerebral artery occlusion (pMCAO) by the macrosphere model and monitored by MRI and PET for 28 or 56 days, followed by immunohistochemical endpoint analysis. To our knowledge, this is the first study providing USPIO-MRI data in the chronic phase up to 8 weeks after stroke. RESULTS: Phagocytes with internalized USPIOs induced MRI-T2(∗) signal alterations in the brain. Combined analysis with [(11)C]PK11195-PET allowed quantification of phagocytic activity and other neuroinflammatory processes. From 4 weeks after induction of ischemia, inflammation was dominated by phagocytes. Immunohistochemistry revealed colocalization of Iba1+ microglia with [(11)C]PK11195 and ED1/CD68 with USPIOs. USPIO-related iron was distinguished from alternatively deposited iron by assessing MRI before and after USPIO application. Tissue affected by non-phagocytic inflammation during the first week mostly remained in a viably vital but remodeled state after 4 or 8 weeks, while phagocytic activity was associated with severe injury and necrosis accordingly. CONCLUSIONS: We conclude that the combined approach of USPIO-MRI and [(11)C]PK11195-PET allows to observe post-stroke inflammatory processes in the living animal in an intraindividual and longitudinal fashion, predicting long-term tissue fate. The non-invasive imaging methods do not affect the immune system and have been applied to human subjects before. Translation into clinical applications is therefore feasible.


Assuntos
Isquemia Encefálica/imunologia , Encéfalo/imunologia , Acidente Vascular Cerebral/imunologia , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/patologia , Proteínas de Ligação ao Cálcio/metabolismo , Radioisótopos de Carbono , Doença Crônica , Modelos Animais de Doenças , Compostos Férricos , Imuno-Histoquímica , Infarto da Artéria Cerebral Média , Isoquinolinas , Imageamento por Ressonância Magnética , Masculino , Proteínas dos Microfilamentos/metabolismo , Microglia/patologia , Microglia/fisiologia , Fagocitose/fisiologia , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Ratos Wistar , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia
14.
ScientificWorldJournal ; 2014: 452089, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25401140

RESUMO

BACKGROUND: Radiotherapy (RT) in patients with pancreatic cancer is still a controversial subject and its benefit in inoperable stages of locally advanced pancreatic cancer (LAPC), even after induction chemotherapy, remains unclear. Modern radiation techniques such as image-guided radiotherapy (IGRT) and intensity-modulated radiotherapy (IMRT) may improve effectiveness and reduce radiotherapy-related toxicities. METHODS: Patients with LAPC who underwent radiotherapy after chemotherapy between 09/2004 and 05/2013 were retrospectively analyzed with regard to preradiation chemotherapy (PRCT), modalities of radiotherapy, and toxicities. Progression-free (PFS) and overall survival (OS) were estimated by Kaplan-Meier curves. RESULTS: 15 (68%) women and 7 men (median age 64 years; range 40-77) were identified. Median duration of PRCT was 11.1 months (range 4.3-33.0). Six patients (27%) underwent conventional RT and 16 patients (73%) advanced IMRT and IGRT; median dosage was 50.4 (range 9-54) Gray. No grade III or IV toxicities occurred. Median PFS (estimated from the beginning of RT) was 5.8 months, 2.6 months in the conventional RT group (conv-RT), and 7.1 months in the IMRT/IGRT group (P = 0.029); median OS was 11.0 months, 4.2 months (conv-RT), and 14.0 months (IMRT/IGRT); P = 0.141. Median RT-specific PFS for patients with prolonged PRCT > 9 months was 8.5 months compared to 5.6 months for PRCT < 9 months (P = 0.293). This effect was translated into a significantly better median RT-specific overall survival of patients in the PRCT > 9 months group, with 19.0 months compared to 8.5 months in the PRCT < 9 months group (P = 0.049). CONCLUSIONS: IGRT and IMRT after PRCT are feasible and effective options for patients with LAPC after prolonged preradiation chemotherapy.


Assuntos
Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/radioterapia , Radioterapia Guiada por Imagem/métodos , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Antineoplásicos/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico , Estudos Retrospectivos
15.
Neuroimage ; 94: 250-262, 2014 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-24657778

RESUMO

Brain function critically relies on the supply with energy substrates (oxygen and glucose) via blood flow. Alterations in energy demand as during neuronal activation induce dynamic changes in substrate fluxes and blood flow. To study the complex system that regulates cerebral metabolism requires the combination of methods for the simultaneous assessment of multiple parameters. We developed a multimodal imaging device to combine positron emission tomography (PET) with laser speckle imaging (LSI) and RGB reflectometry (RGBR). Depending on the radiotracer, PET provides 3-dimensional quantitative information of specific molecular processes, while LSI and RGBR measure cerebral blood flow (CBF) and hemoglobin oxygenation at high temporal and spatial resolution. We first tested the functional capability of each modality within our system and showed that interference between the modalities is negligible. We then cross-calibrated the system by simultaneously measuring absolute CBF using (15)O-H2O PET (CBF(PET)) and the inverse correlation time (ICT), the LSI surrogate for CBF. ICT and CBF(PET) correlated in multiple measurements in individuals as well as across different animals (R(2)=0.87, n=44 measurements) indicating that ICT can be used for absolute quantitative assessment of CBF. To demonstrate the potential of the combined system, we applied it to cortical spreading depression (CSD), a wave of transient cellular depolarization that served here as a model system for neurovascular and neurometabolic coupling. We analyzed time courses of hemoglobin oxygenation and CBF alterations coupled to CSD, and simultaneously measured regional uptake of (18)F-2-fluoro-2-deoxy-D-glucose ((18)F-FDG) used as a radiotracer for regional glucose metabolism, in response to a single CSD and to a cluster of CSD waves. With this unique combination, we characterized the changes in cerebral metabolic rate of oxygen (CMRO2) in real-time and showed a correlation between (18)F-FDG uptake and the number of CSD waves that passed the local tissue. Finally, we examined CSD spontaneously occurring during focal ischemia also referred to as peri-infarct depolarization (PID). In the vicinity of the ischemic territory, we observed PIDs that were characterized by reduced CMRO2 and increased oxygen extraction fraction (OEF), indicating a limitation of oxygen supply. Simultaneously measured PET showed an increased (18)F-FDG uptake in these regions. Our combined system proved to be a novel tool for the simultaneous study of dynamic spatiotemporal alterations of cortical blood flow, oxygen metabolism and glucose consumption under normal and pathologic conditions.


Assuntos
Mapeamento Encefálico/instrumentação , Encéfalo/metabolismo , Glucose/metabolismo , Microscopia Confocal/instrumentação , Oxigênio/metabolismo , Fotometria/instrumentação , Tomografia por Emissão de Pósitrons/instrumentação , Animais , Isquemia Encefálica/metabolismo , Circulação Cerebrovascular , Colorimetria/instrumentação , Depressão Alastrante da Atividade Elétrica Cortical/fisiologia , Desenho de Equipamento , Análise de Falha de Equipamento , Ratos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Distribuição Tecidual , Imagens com Corantes Sensíveis à Voltagem/instrumentação
16.
Curr Mol Med ; 14(2): 246-54, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24467204

RESUMO

The caspases are a family of ubiquitously expressed cysteine proteases best known for their roles in programmed cell death. However, caspases play a number of other roles in vertebrates. In the case of caspase-8, loss of expression is an embryonic lethal phenotype, and caspase-8 plays roles in suppressing cellular necrosis, promoting differentiation and immune signaling, regulating autophagy, and promoting cellular migration. Apoptosis and migration require localization of caspase-8 in the periphery of the cells, where caspase-8 acts as part of distinct biosensory complexes that either promote migration in appropriate cellular microenvironments, or cell death in inappropriate settings. In the cellular periphery, caspase-8 interacts with components of the focal adhesion complex in a tyrosine-kinase dependent manner, promoting both cell migration in vitro and metastasis in vivo. Mechanistically, caspase-8 interacts with components of both focal adhesions and early endosomes, enhancing focal adhesion turnover and promoting rapid integrin recycling to the cell surface. Clinically, this suggests that the expression of caspase-8 may not always be a positive prognostic sign, and that the role of caspase-8 in cancer progression is likely context-dependent.


Assuntos
Caspase 8/metabolismo , Movimento Celular/fisiologia , Animais , Apoptose/genética , Apoptose/fisiologia , Caspase 8/genética , Movimento Celular/genética , Humanos
17.
Phys Chem Chem Phys ; 16(21): 9700-12, 2014 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-24419644

RESUMO

An overview is given on advanced magnetic resonance strategies and techniques, both nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR), as applied to nanostructured soft matter. In addition, the combination of the two forms of spectroscopy to enhance signal intensity in NMR by means of dynamic nuclear polarization (DNP) is described. It is shown how these techniques can provide unique information on the structure of soft matter as well as the local dynamics of the constituents. Examples of recent applications are described, including dendronized and thermoresponsive polymers, hydrogels, synthetic and bio-inspired polymers, as well as polypeptides and biopolymers.

18.
Cancer Radiother ; 17(7): 664-7, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24176665

RESUMO

PURPOSE: This study investigated image-guided patient positioning during frameless, mask-based, single-fraction stereotactic radiosurgery of intracranial lesions and intrafractional translational and rotational variations in patient positions. PATIENTS AND METHODS: A non-invasive head and neck thermoplastic mask was used for immobilization. The Exactrac/Novalis Body system (BrainLAB AG, Germany) was used for kV X-ray imaging guided positioning. Intrafraction displacement data, obtained by imaging after each new table position, were evaluated. RESULTS: There were 269 radiosurgery treatments performed on 190 patients and a total of 967 setups within different angles. The first measured error after each table rotation (mean 2.6) was evaluated (698 measurements). Intrafraction translational errors were (1 standard deviation [SD]) on average 0.8, 0.8, and 0.7mm for the left-right, superior-inferior, and anterior-posterior directions, respectively, with a mean 3D-vector of 1.0mm (SD 0.9mm) and a range from -5mm to +5mm. On average, 12%, 3%, and 1% of the translational deviations exceeded 1, 2, and 3mm, respectively, in the three directions. CONCLUSION: The range of intrafraction patient motion in frameless image-guided stereotactic radiosurgery is often not fully mapped by pre- and post-treatment imaging. In the current study, intrafraction motion was assessed by performing measurements at several time points during the course of stereotactic radiosurgery. It was determined that 12% of the intrafraction values in the three dimensions are above 1mm, the usual safety margin applied in stereotactic radiosurgery.


Assuntos
Neoplasias Encefálicas/cirurgia , Radiocirurgia/métodos , Radioterapia Guiada por Imagem , Humanos , Imobilização/instrumentação , Posicionamento do Paciente , Estudos Prospectivos
19.
Adv Exp Med Biol ; 789: 427-433, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23852525

RESUMO

We demonstrate a system for the simultaneous imaging of cortical blood flow and haemoglobin oxygenation by laser speckle contrast analysis (LASCA) and RGB reflectometry. The sensitivity of the system was tested by observing changes of haemoglobin oxygenation and blood flow in rats in response to ischaemic stroke, hypercapnia, hyperoxia, hypoxia, cortical spreading depression and cortical activation following forepaw stimulation.


Assuntos
Córtex Cerebral/irrigação sanguínea , Circulação Cerebrovascular/fisiologia , Hemoglobinas/metabolismo , Animais , Depressão Alastrante da Atividade Elétrica Cortical/fisiologia , Diagnóstico por Imagem/métodos , Hipercapnia/metabolismo , Hipercapnia/fisiopatologia , Hiperóxia/metabolismo , Hiperóxia/fisiopatologia , Lasers , Oxigênio/metabolismo , Ratos , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/fisiopatologia
20.
Int J Cosmet Sci ; 35(5): 448-57, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23651429

RESUMO

OBJECTIVE: Stem cells have the ability to renew themselves and differentiate into various cell types. For this reason, numerous research groups have been studying these cells for their therapeutic potential. Some of the therapies, however, are not producing the expected results because of contamination by other cell types, especially by fibroblasts. In the cosmetic industry, stem cells are used to test the efficacy of anti-ageing and rejuvenation products. The purpose of this work was to gain a better understanding of the differences in phenotype, in gene expression associated with stem cells, in the pattern of cell surface proteins and in the differentiation capacity of adipose-derived stem cells, of skin-derived stem cells and of commercially available fibroblasts. METHODS: In this study, we compared fibroblasts with mesenchymal stem cells derived from bone marrow, skin (dermis) and adipose tissue, to assess the differentiation potential of fibroblasts. Dermal and adipose stem cells were isolated from aesthetic surgery patients, and fibroblasts were obtained from a commercial source. The following parameters were used in this study: immunophenotypic profile (positive: CD29, CD73, CD90 and CD105; negative: CD14, CD45 and HLA-DR); differentiation into osteoblastic, chondrogenic and adipogenic cell types; and PCR array to analyse the gene expression of cells isolated from different culture passages. RESULTS: Fibroblasts express the same cell immunophenotypic markers, as well as the genes that are known to be expressed in stem cells, and were shown to be expressed also in adipose and dermis stem cells. Fibroblasts are also able to differentiate into the three cell lineages mentioned above, that is, adipocytes, osteocytes and chondrocytes. CONCLUSION: Human dermal fibroblasts have a potential to adhere to plastic surfaces and differentiate into other cell types. However, for stem cells intended to be used in cosmetics, experiments conducted with contaminated fibroblasts may produce poor or even falsely negative results for the efficacy of the active ingredient or formulation and thus conceal their promising effects as anti-ageing and skin rejuvenation products.


Assuntos
Tecido Adiposo/citologia , Fibroblastos/citologia , Células-Tronco Mesenquimais/citologia , Pele/citologia , Tecido Adiposo/fisiologia , Diferenciação Celular/fisiologia , Feminino , Fibroblastos/fisiologia , Citometria de Fluxo , Humanos , Imunofenotipagem , Células-Tronco Mesenquimais/fisiologia , RNA/química , RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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