Stress distribution in the trochlear notch

n 16 cadaver humeroulnar joints, the distribution of subchondral mineralisation was assessed by CT osteoabsorptiometry and the position and size of the contact areas by polyether casting under loads of 10 N to 1280 N. Ulnas with separate olecranon and coronoid cartilaginous surfaces showed matching bicentric patterns of mineralisation. Under small loads there were separate contact areas on the olecranon and coronoid surfaces; these areas merged centrally as the load increased. They occupied as little as 9% of the total articular surface at 10 N and up to 73% at 1280 N. Ulnas with continuous cartilaginous surfaces also had density patterns with two maxima but those were less prominent, and in these specimens the separate contact areas merged at lower loads. The findings indicate a physiological incongruity of the articular surfaces which may serve to optimise the distribution of stress

Physiological incongruity of the humero-ulnar joint

Investigations into the distribution of subchondral bone density in the human elbow have suggested that the geometry of the trochlear notch deviates from a perfect fit with the trochlea, and that the load is transmitted ventrally and dorsally rather than through the centre of the humero-ulnar joint. We therefore decided to make a quantitative assessment of the degree of incongruity between the two components in 15 human specimens (age distribution 60 to 93 years) with different types of joint surface. Polyether casts of the joint cavity were prepared under loads of 10,40,160 and 640 N. The thickness of the casts was then measured at 50 predetermined points, and an area distribution of the width of the joint space represented in a two-dimensional template of the trochlear notch. The reproducibility of this procedure was tested by image analysis. At a load of 10 N, only a narrow space was present ventrally and dorsally in the joint, but in the depths of the trochlear notch a width of 0.5 to 1 mm was recorded in the centre, and up to 3 mm at its medial and lateral edges. Specimens with continuous articular cartilage showed a lower degree of incongruity than those with a divided articular surface. As the load was increased to 640 N, however, the original incongruity between the articular surfaces disappeared almost completely. The joint surfaces became more congruous, probably because of the viscoelastic properties of the articular cartilage and the subchondral bone, and the contact areas merged in the centre of the joint. It is suggested that this physiological incongruity brings about an optimal distribution of stress over the articular surface during the transmission of the load, and it may lead to better nourishment of the articular cartilage by providing intermittent mechanical stimulation and circulation of the synovial fluid

Islets of Langerhans Are Protected from Inflammatory Cell Recruitment during Reperfusion of Rat Pancreas Grafts

Background: Ischemia/reperfusion (I/R) injury plays a pivotal role in the development of graft pancreatitis, with ischemia time representing one of its crucial factors. However, it is unclear, whether exocrine and endocrine tissue experience similar inflammatory responses during pancreas transplantation (PTx). This study evaluated inflammatory susceptibilities of islets of Langerhans (ILH) and exocrine tissue after different preservation periods during early reperfusion. Methods: PTx was performed in rats following 2 h (2h-I) or 18 h (18h-I) preservation. Leukocyte-endothelial cell interactions (LEI) were analyzed in venules of acinar tissue and ILH in vivo over 2 h reperfusion. Nontransplanted animals served as controls. Tissue samples were analyzed by histomorphometry. Results: In exocrine venules leukocyte rolling predominated in the 2h-I group. In the 18h-I group, additionally, high numbers of adherent leukocytes were found. Histology revealed significant edema formation and leukocyte extravasation in the 18h-I group. Notably, LEI in postcapillary venules of ILH were significantly lower. Leukocyte rolling was only moderately enhanced and few leukocytes were found adherent. Histology revealed minor leukocyte extravasation. Conclusion: Ischemia time contributes decisively to the extent of the I/R-injury in PTx. However, ILH have a significantly lower susceptibility towards I/R, even when inflammatory reactions in adjacent exocrine tissue are evident. Copyright (C) 2010 S. Karger AG, Base

GSH Attenuates Organ Injury and Improves Function after Transplantation of Fatty Livers

Ischemia-reperfusion injury (IRI) is increased after transplantation of steatotic livers. Since those livers are increasingly used for transplantation, protective strategies must be developed. Reactive oxygen species (ROS) play a key role in hepatic IRI. In lean organs, glutathione (GSH) is an efficient scavenger of ROS, diminishing IRI. The aim of this study was to evaluate whether GSH also protects steatotic allografts from IRI following transplantation. Fatty or lean livers were explanted from 10-week-old obese or lean Zucker rats and preserved (obese 4 h, lean 24 h) in hypothermic University of Wisconsin solution. Arterialized liver transplantation was then performed in lean syngeneic Zucker rats. Recipients of fatty livers were treated with GSH (200 mu mol/h/kg) or saline during reperfusion (2 h, n = 5). Parameters of hepatocellular damage and bile flow were measured. Transplantation of steatotic livers enhanced early reperfusion injury compared to lean organs as measured by increased aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase plasma levels. Bile flow was also reduced in steatotic grafts. Intravenous administration of GSH effectively decreased liver damage in fatty allografts and resulted in improved bile flow. Intravenous application of GSH effectively reduces early IRI in steatotic allografts and improves recovery of these marginal donor organs following transplantation. Copyright (C) 2010 S. Karger AG, Base

Therapeutic T cells induce tumor-directed chemotaxis of innate immune cells through tumor-specific secretion of chemokines and stimulation of B16BL6 melanoma to secrete chemokines

Background: The mechanisms by which tumor-specific T cells induce regression of established metastases are not fully characterized. In using the poorly immunogenic B16BL6-D5 (D5) melanoma model we reported that T cell-mediated tumor regression can occur independently of perforin, IFN-gamma or the combination of both. Characterization of regressing pulmonary metastases identified macrophages as a major component of the cells infiltrating the tumor after adoptive transfer of effector T cells. This led us to hypothesize that macrophages played a central role in tumor regression following T-cell transfer. Here, we sought to determine the factors responsible for the infiltration of macrophages at the tumor site. Methods: These studies used the poorly immunogenic D5 melanoma model. Tumor-specific effector T cells, generated from tumor vaccine-draining lymph nodes (TVDLN), were used for adoptive immunotherapy and in vitro analysis of chemokine expression. Cellular infiltrates into pulmonary metastases were determined by immunohistochemistry. Chemokine expression by the D5 melanoma following co-culture with T cells, IFN-gamma or TNF-alpha was determined by RT-PCR and ELISA. Functional activity of chemokines was confirmed using a macrophage migration assay. T cell activation of macrophages to release nitric oxide (NO) was determined using GRIES reagent. Results: We observed that tumor-specific T cells with a type 1 cytokine profile also expressed message for and secreted RANTES, MIP-1 alpha and MIP-1 beta following stimulation with specific tumor. Unexpectedly, D5 melanoma cells cultured with IFN-gamma or TNF-alpha, two type 1 cytokines expressed by therapeutic T cells, secreted Keratinocyte Chemoattractant (KC), MCP-1, IP-10 and RANTES and expressed mRNA for MIG. The chemokines released by T cells and cytokine-stimulated tumor cells were functional and induced migration of the DJ2PM macrophage cell line. Additionally, tumor-specific stimulation of wt or perforin-deficient (PKO) effector T cells induced macrophages to secrete nitric oxide (NO), providing an additional effector mechanism for T cell-mediated tumor regression. Conclusion: These data suggest two possible sources for chemokine secretion that stimulates macrophage recruitment to the site of tumor metastases. Both appear to be initiated by T cell recognition of specific antigen, but one is dependent on the tumor cells to produce the chemokines that recruit macrophages