The role of the 51 integrin as mechanotransducer in dynamically compressed tissue-engineered cartilage constructs

Abstract onl

The role of the 51 integrin as mechanotransducer in dynamically compressed tissue-engineered cartilage constructs

Abstract onl

The alpha5beta1 integrin as mechanotransducer in chondrocytes

Mechanical loading has been proposed as a mechanism for improving the functionality of engineered cartilage tissue. However, the precise mechanotransduction pathways are unknown. Recent studies have shown that integrins can act as mechanoreceptors in articular cartilage. In this study, we examined the role of integrin a5ß1 in the anoregulation of both ECM gene expression and ECM protein synthesis in tissue-engineered hondrocyte/agarose constructs. Chondrocytes, isolated and seeded in 3% agarose constructs, were compressed at 0.33 and 1 Hz, in the presence or absence of GRGDSP (a blocker for integrin a5ß1). mRNA levels for aggrecan, collagen II and MMP-3 were determined at several time points up to 24 hours post-stimulation. Cell viability, DNA and sGAG content were determined at several time points up to 28 days post-stimulation. mRNA levels for all genes were upregulated upon loading, except for collagen II, loaded at 0.33 Hz. Incubation with GRGDSP counteracted upregulation. sGAG levels were significantly lower in constructs loaded at 0.33 Hz compared to the unstrained control at day 28. In contrast, loading at 1 Hz caused a significant increase in sGAG deposition at this timepoint, which was counteracted by blocking the a5ß1 integrin. We conclude that the a5ß1 integrin acts as a mechanotransducer in the regulation of both ECM gene expression and matrix biosynthesis for chondrocytes seeded in agarose under the loading regimes applied. However, this regulation appears frequency dependent

Remifentanil in the intensive care unit: tolerance and acute withdrawal syndrome after prolonged

SEDATION in the intensive care unit should be minimized to reduce the duration of mechanical ventilation and its related complications.1 The drug regimen would ideally allow rapid awakening, to perform neurologic and respiratory evaluation on a daily basis.2,3 In this context, remifentanil, with its unique pharmacokinetic profile, should be considered an agent of choice.4,5 However, acute tolerance and even hyperalgesic response have been observed after opioid administration.6-8 In addition, withdrawal syndrome after cessation of opioid-based sedation has been seen in the intensive care unit setting.9-11 We report three cases of severe and fast-onset withdrawal syndrome, with signs of acute tolerance, after remifentanil-based sedation of between 2 and 30 days' duration, requiring reintroduction of remifentanil and then tapering over 24-48

Reconstruction of an average cortical column in silico

The characterization of individual neurons by Golgi and Cajal has been the basis of neuroanatomy for a century. A new challenge is to anatomically describe, at cellular resolution, complete local circuits that can drive behavior. In this essay, we review the possibilities to obtain a model cortical column by using in vitro and in vivo pair recordings, followed by anatomical reconstructions of the projecting and target cells. These pairs establish connection modules that eventually may be useful to synthesize an average cortical column in silico. Together with data on sensory evoked neuronal activity measured in vivo, this will allow to model the anatomical and functional cellular basis of behavior based on more realistic assumptions than previously attempted

The role of integrin alpha5beta1 mechanotransducer in chondrocytes embedded in agarose

Abstract only

The role of integrin alpha5beta1 mechanotransducer in chondrocytes embedded in agarose

Abstract only