RESUMO
We present a radiology-pathology case series of 3 patients with coronavirus disease 2019 (COVID-19) with acute ischemic stroke due to fulminant carotid thrombosis overlying mild atherosclerotic plaque and propose a novel stroke mechanism: COVID-associated carotid atherothrombosis.
Assuntos
Doenças das Artérias Carótidas/virologia , Trombose das Artérias Carótidas/etiologia , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Acidente Vascular Cerebral/etiologia , Idoso , Betacoronavirus , COVID-19 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Placa Aterosclerótica/patologia , Fatores de Risco , SARS-CoV-2RESUMO
OBJECTIVES: Recent studies have shown that systemic injection of rapamycin can prevent the development of osteoarthritis (OA)-like changes in human chondrocytes and reduce the severity of experimental OA. However, the systemic injection of rapamycin leads to many side effects. The purpose of this study was to determine the effects of intra-articular injection of Torin 1, which as a specific inhibitor of mTOR which can cause induction of autophagy, is similar to rapamycin, on articular cartilage degeneration in a rabbit osteoarthritis model and to investigate the mechanism of Torin 1's effects on experimental OA. METHODS: Collagenase (type II) was injected twice into both knees of three-month-old rabbits to induce OA, combined with two intra-articular injections of Torin 1 (400 nM). Degeneration of articular cartilage was evaluated by histology using the Mankin scoring system at eight weeks after injection. Chondrocyte degeneration and autophagosomes were observed by transmission electron microscopy. Matrix metallopeptidase-13 (MMP-13) and vascular endothelial growth factor (VEGF) expression were analysed by quantitative RT-PCR (qPCR).Beclin-1 and light chain 3 (LC3) expression were examined by Western blotting. RESULTS: Intra-articular injection of Torin 1 significantly reduced degeneration of the articular cartilage after induction of OA. Autophagosomes andBeclin-1 and LC3 expression were increased in the chondrocytes from Torin 1-treated rabbits. Torin 1 treatment also reduced MMP-13 and VEGF expression at eight weeks after collagenase injection. CONCLUSION: Our results demonstrate that intra-articular injection of Torin 1 reduces degeneration of articular cartilage in collagenase-induced OA, at least partially by autophagy activation, suggesting a novel therapeutic approach for preventing cartilage degeneration and treating OA.Cite this article: N-T. Cheng, A. Guo, Y-P. Cui. Intra-articular injection of Torin 1 reduces degeneration of articular cartilage in a rabbit osteoarthritis model. Bone Joint Res 2016;5:218-224. DOI: 10.1302/2046-3758.56.BJR-2015-0001.
RESUMO
In many parts of human body, air-filled spaces are components of normal anatomical structures, such as nasopharynx and paranasal sinuses, and the inclusion of these spaces in radiation treatment fields may create inhomogeneous dose distribution, due to the loss of scattering electron equilibrium, the lack of backscatter and the alteration in primary beam attenuation. Accurate determination or measurement of dose in the region of irregular air spaces has been experimentally difficult. However, tumors growing on the surface of the air cavities do cause serious concern by conscientious radiation therapists and physicist about the possibility of underdose. Using the models of simulated air cavities, combined air cavity and air channel, and taking measurement with a small window parallel plate ionization chamber in solid phantoms, it is found that the air spaces in the human body will cause underdose or overdose at the exit air space surface for 10MV X-ray and Co-60 r-ray. Surface dose were evaluated by a gain/loss factors (G/L) which was defined as the ratio of exit air space surface dose and the dose measured in a same but homogeneous phantom. The G/L factors are greater than 1.0 (overdose) where the air spaces are much smaller than radiation field sizes and are less than 1.0 (underdose) in extreme situations where the air spaces are larger than radiation field sizes and where the scattered volume of cavity wall in the treatment fields in also small. In addition, these effects of overdose and underdose are enhanced by increasing air space thickness and higher photon energy. We suggest that the radiation therapists and clinical physicists be cautious in applying these useful guidelines for treatment planning.
Assuntos
Doses de Radiação , Radioisótopos de Cobalto , Humanos , Modelos Estruturais , Raios XRESUMO
A radiation beam incident on an irregular or sloping surface produces skewing of isodose curves and may give rise to unacceptable nonuniformity of the dose distribution within the target volume or cause excessive irradiation of sensitive tissues. The concept of using a compensator, first introduced by Ellis, to circumvent the skewness of isodose curves was elegant. Other workers followed suit elaborating further and extending the procedures. The treatment of chest wall tumors is of special interest and compensators were frequently used in their management. The compensators of aluminum and copper were systematically examined for 6 and 10 MV X-rays. Compensating thickness ratios was determined from equivalent dose measurement at compensating depth by placing compensator at the regular blocking tray for maintaining the skin sparing feature of high energy photon beams. The compensator must compensate not only for the reduction of the primary beam attenuation due to tissue deficit, but also for the loss of scattering by the missing tissues. It was found that the compensating thickness ratios (CTR) was not a constant value and was dependent on the tissue deficit, field size, compensating depth and the material of compensator, but was independent of the energy. As the tissue deficit is increased, the CTR decreases, since the loss of scattering for the deficit volume can be compensated by the lowered attenuation of the compensator. As the field size is increased, the CTR decreases. From the study of central axis depth dose for various deficit thickness, normalized at the median plane of no tissue deficit, it was found that compensator can compensate the dose accurately to one depth only and the compensation to other depth is approximate, and that the compensating error is increased with greater tissue deficit and further depth. The effectiveness of the compensating system with a stair-step polystyrene phantom representative of varying tissue deficits over a small treatment field (20 cm x 20 cm) was also studied with film dosimetry and the error was within 3%. The compensator thickness ratios must be measured in different radiation beams from different treatment machines and in different irradiation conditions because there are major difference between the CTR data obtained directly from experiments and the data besed on calculation from attenuation coefficient mu, physical density rho or electronic density, rho e. The specific CTR reported for aluminum and copper in the literature should only be used as a guideline.