The principle of regulation in biology--from bone to eating behavior.

Cell physiology and molecular biology typically follow a reductionistic approach in science. In the last decade, molecular principles and pathogenetic factors involved in the development of many diseases have been successfully discovered. Therefore, early biological concepts based on systemic and cybernetic thoughts have been largely overshadowed by these more recent molecular and pathogenetic factors. This review highlights discoveries on bone development and hypothalamic controlled feeding and eating behavior with a cybernetic and systemic perspective. Interestingly, ancient ideas on bone development and hypothalamic function are still reasonable considerations to embed new molecular discoveries into a systemic concept of principles organizing nature.     

Obstructive and restrictive spirometric patterns: fixed cut-offs for FEV1/FEV6 and FEV6.

The purpose of this study was to determine fixed cut-off points for forced expiratory volume in one second (FEV(1))/FEV(6) and FEV(6) as an alternative for FEV(1)/forced vital capacity (FVC) and FVC in the detection of obstructive and restrictive spirometric patterns, respectively. For the study, a total of 11,676 spirometric examinations, which took place on Caucasian subjects aged between 20-80 yrs, were analysed. Receiver-operator characteristic curves were used to determine the FEV(1)/FEV(6) ratio and FEV(6) value that corresponded to the optimal combination of sensitivity and specificity, compared with the commonly used fixed cut-off term for FEV(1)/FVC and FVC. The data from the current study indicate that FEV(1)/ FEV(6) <73% and FEV(6) <82% predicted can be used as a valid alternative for the FEV(1)/FVC <70% and FVC <80% pred cut-off points for the detection of obstruction and restriction, respectively. The statistical analysis demonstrated very good, overall, agreement between the two categorisation schemes. For the spirometric diagnosis of airway obstruction (prevalence of 45.9%), FEV(1)/FEV(6) sensitivity and specificity were 94.4 and 93.3%, respectively; the positive and negative predictive values were 92.2 and 95.2%, respectively. For the spirometric detection of a restrictive pattern (prevalence of 14.9%), FEV(6) sensitivity and specificity were 95.9 and 98.6%, respectively; the positive and negative predictive values were 92.2 and 99.3%, respectively. This study demonstrates that forced expiratory volume in one second/forced expiratory volume in six seconds <73% and forced expiratory volume in six seconds <82% predicted, can be used as valid alternatives to forced expiratory volume in one second/forced vital capacity <70% and forced vital capacity <80% predicted, as fixed cut-off terms for the detection of an obstructive or restrictive spirometric pattern in adults.     

Modifying integra as a regeneration template in deep tissue planes.

Contour defects resulting in deformity caused by lack of tissue can be improved by conventional surgery using autologous tissue, but there is always a donor site morbidity. Integra has been available since the early 1980's for use in acute burns and more recently in reconstruction. It has been shown histologically to act as a tissue regeneration template. The regenerated dermis is buried under an autologous thin split-skin graft. In this study, the principle of burying Integra (without the silicone layer) has been applied to deep tissue defects in 12 reconstructive cases. Such regenerated tissues survive at least 3 years after burying. Modification to the technique to avoid visible edges are being developed.     

Particulate endocytosis mediates biological responses of human mesenchymal stem cells to titanium wear debris.

Continual loading and articulation cycles undergone by metallic (e.g., titanium) alloy arthroplasty prostheses lead to liberation of a large number of metallic debris particulates, which have long been implicated as a primary cause of periprosthetic osteolysis and postarthroplasty aseptic implant loosening. Long-term stability of total joint replacement prostheses relies on proper integration between implant biomaterial and osseous tissue, and factors that interfere with this integration are likely to cause osteolysis. Because multipotent mesenchymal stem cells (MSCs) located adjacent to the implant have an osteoprogenitor function and are critical contributors to osseous tissue integrity, when their functions or activities are compromised, osteolysis will most likely occur. To date, it is not certain or sufficiently confirmed whether MSCs endocytose titanium particles, and if so, whether particulate endocytosis has any effect on cellular responses to wear debris. This study seeks to clarify the phenomenon of titanium endocytosis by human MSCs (hMSCs), and investigates the influence of endocytosis on their activities. hMSCs incubated with commercially pure titanium particles exhibited internalized particles, as observed by scanning electron microscopy and confocal laser scanning microscopy, with time-dependent reduction in the number of extracellular particles. Particulate endocytosis was associated with reduced rates of cellular proliferation and cell-substrate adhesion, suppressed osteogenic differentiation, and increased rate of apoptosis. These cellular effects of exposure to titanium particles were reduced when endocytosis was inhibited by treatment with cytochalasin D, and no significant effect was seen when hMSCs were treated only with conditioned medium obtained from particulate-treated cells. These findings strongly suggest that the biological responses of hMSCs to wear debris are triggered primarily by the direct endocytosis of titanium particulates, and not mediated by secreted soluble factors. In this manner, therapeutical approaches that suppress particle endocytosis could reduce the bioreactivity of hMSCs to particulates, and enhance long-term orthopedic implant prognosis by minimizing wear-debris periprosthethic osteolysis.