The effects of dynamic loading on the intervertebral disc

Loading is important to maintain the balance of matrix turnover in the intervertebral disc (IVD). Daily cyclic diurnal assists in the transport of large soluble factors across the IVD and its surrounding circulation and applies direct and indirect stimulus to disc cells. Acute mechanical injury and accumulated overloading, however, could induce disc degeneration. Recently, there is more information available on how cyclic loading, especially axial compression and hydrostatic pressure, affects IVD cell biology. This review summarises recent studies on the response of the IVD and stem cells to applied cyclic compression and hydrostatic pressure. These studies investigate the possible role of loading in the initiation and progression of disc degeneration as well as quantifying a physiological loading condition for the study of disc degeneration biological therapy. Subsequently, a possible physiological/beneficial loading range is proposed. This physiological/beneficial loading could provide insight into how to design loading regimes in specific system for the testing of various biological therapies such as cell therapy, chemical therapy or tissue engineering constructs to achieve a better final outcome. In addition, the parameter space of 'physiological' loading may also be an important factor for the differentiation of stem cells towards most ideally 'discogenic' cells for tissue engineering purpose.

A novel interface for hybrid mock circulations to evaluate ventricular assist devices

This paper presents a novel mock circulation for the evaluation of ventricular assist devices (VADs), which is based on a hardware-in-the-loop concept. A numerical model of the human blood circulation runs in real time and computes instantaneous pressure, volume, and flow rate values. The VAD to be tested is connected to a numerical-hydraulic interface, which allows the interaction between the VAD and the numerical model of the circulation. The numerical-hydraulic interface consists of two pressure-controlled reservoirs, which apply the computed pressure values from the model to the VAD, and a flow probe to feed the resulting VAD flow rate back to the model. Experimental results are provided to show the proper interaction between a numerical model of the circulation and a mixed-flow blood pump.

Contrast-enhanced transcranial Doppler ultrasound for diagnosis of patent foramen ovale

The suspected cause of clinical manifestations of patent foramen ovale (PFO) is a transient or a permanent right-to-left shunt (RLS). Contrast-enhanced transcranial Doppler ultrasound (c-TCD) is a reliable alternative to transesophageal echocardiography (TEE) for diagnosis of PFO, and enables also the detection of extracardiac RLS. The air-containing echo contrast agents are injected intravenously and do not pass the pulmonary circulation. In the presence of RLS, the contrast agents bypass the pulmonary circulation and cause microembolic signals (MES) in the basal cerebral arteries, which are detected by TCD. The two main echo contrast agents in use are agitated saline and D-galactose microparticle solutions. At least one middle cerebral artery (MCA) is insonated, and the ultrasound probe is fixed with a headframe. The monitored Doppler spectra are stored for offline analysis (e.g., videotape) of the time of occurrence and number of MES, which are used to assess the size and functional relevance of the RLS. The examination is more sensitive, if both MCAs are investigated. In the case of negative testing, the examination is repeated using the Valsalva maneuver. Compared to TEE, c-TCD is more comfortable for the patient, enables an easier assessment of the size and functional relevance of the RLS, and allows also the detection of extracardiac RLS. However, c-TCD cannot localize the site of the RLS. Therefore, TEE and TCD are complementary methods and should be applied jointly in order to increase the diagnostic accuracy for detecting PFO and other types of RLS.

Extracts of Lindera obtusiloba induce antifibrotic effects in hepatic stellate cells via suppression of a TGF-beta-mediated profibrotic gene expression pattern

Liver fibrosis is characterized by high expression of the key profibrogenic cytokine transforming growth factor (TGF)-beta and the natural tissue inhibitor of metalloproteinases (TIMP)-1, leading to substantial accumulation of extracellular matrix. Liver fibrosis originates from various chronic liver diseases, such as chronic viral hepatitis that, to date, cannot be treated sufficiently. Thus, novel therapeutics, for example, those derived from Oriental medicine, have gained growing attention. In Korea, extracts prepared from Lindera obtusiloba are used for centuries for treatment of inflammation, improvement of blood circulation and prevention of liver damage, but experimental evidence of their efficacy is lacking. We studied direct antifibrotic effects in activated hepatic stellate cells (HSCs), the main target cell in the fibrotic liver. L. obtusiloba extract (135 mug/ml) reduced the de novo DNA synthesis of activated rat and human HSCs by about 90%, which was not accompanied by cytotoxicity of HSC, primary hepatocytes and HepG2 cells, pointing to induction of cellular quiescence. As determined by quantitative polymerase chain reaction, simultaneous treatment of HSCs with TGF-beta and L. obtusiloba extract resulted in reduction of TIMP-1 expression to baseline level, disruption of the autocrine loop of TGF-beta autoinduction and increased expression of fibrolytic matrix metalloproteinase (MMP)-3. In addition, L. obtusiloba reduced gelatinolytic activity of HSC by interfering with profibrogenic MMP-2 activity. Since L. obtusiloba extract prevented intracellular oxidative stress experimentally induced by tert-butylhydroperoxide, we concluded that the direct antifibrotic effect of L. obtusiloba extract might be mediated by antioxidant activity. Thus, L. obtusiloba, traditionally used in Oriental medicine, may complement treatment of chronic liver disease.