No abstract

Many pro-inflammatory pathways leading to arthritis have global effects on the immune system rather than only acting locally in joints. The reason behind the regional and patchy distribution of arthritis represents a longstanding paradox. Here we show that biomechanical loading acts as a decisive factor in the transition from systemic autoimmunity to joint inflammation. Distribution of inflammation and erosive disease is confined to mechano-sensitive regions with a unique microanatomy. Curiously, this pathway relies on stromal cells but not adaptive immunity. Mechano-stimulation of mesenchymal cells induces CXCL1 and CCL2 for the recruitment of classical monocytes, which can differentiate into bone-resorbing osteoclasts. Genetic ablation of CCL2 or pharmacologic targeting of its receptor CCR2 abates mechanically-induced exacerbation of arthritis, indicating that stress-induced chemokine release by mesenchymal cells and chemo-attraction of monocytes determines preferential homing of arthritis to certain hot spots. Thus, mechanical strain controls the site-specific localisation of inflammation and tissue damage in arthritis.

Hypothermic machine perfusion (HMP) is experiencing a revival in organ preservation due to the limitations of static cold storage and the need for better preservation of expanded criteria donor organs. For livers, perfusion protocols are still poorly defined, and damage of sinusoidal endothelial cells and heterogeneous perfusion are concerns. In this study, an electrical model of the human liver blood circulation is developed to enlighten internal pressure and flow distributions during HMP. Detailed vascular data on two human livers, obtained by combining vascular corrosion casting, micro-CT-imaging and image processing, were used to set up the electrical model. Anatomical data could be measured up to 5--6 vessel generations in each tree and showed exponential trend lines, used to predict data for higher generations. Simulated flow and pressure were in accordance with literature data. The model was able to simulate effects of pressure-driven HMP on liver hemodynamics and reproduced observations such as flow competition between the hepatic artery and portal vein. Our simulations further indicate that, from a pure biomechanical (shear stress) standpoint, HMP with low pressures should not result in organ damage, and that fluid viscosity has no effect on the shear stress experienced by the liver microcirculation in pressure-driven HMP.

Angiogenesis, i.e. the development and growth of blood vessels, is a major topic of research as it plays an important role in normal development and in various pathologies. Recent evidence revealed the existence of different mechanisms of blood vessel growth, including sprouting and intussusceptive angiogenesis, vascular mimicry, and blood vessel cooption. The latter two have only been observed in tumor growth, but sprouting and intussusceptive angiogenesis also occur in healthy, physiologically growing tissues. Despite this variety of angiogenic mechanisms, most of the current research is focused on the mechanism of sprouting angiogenesis because this mechanism was first described and because most existing experimental models are related to sprouting angiogenesis. Consequently, the mechanism of intussusceptive angiogenesis is often overlooked in angiogenesis research. Here, the mechanism of intussusceptive angiogenesis is reviewed and the current techniques and models for investigating intussusceptive angiogenesis are summarized. In addition, other mechanisms of vascular growth are briefly reviewed.

This paper gives an overview of the anatomical localization and histological characteristics of the tonsils that are present in ten conventional domestic animal species, including the sheep, goat, ox, pig, horse, dog, cat, rabbit, rat, and pigeon. Anatomical macrographs and histological images of the tonsils are shown. Six tonsils can be present in domestic animals, that is, the lingual, palatine, paraepiglottic, pharyngeal, and tubal tonsils and the tonsil of the soft palate. Only in the sheep and goat, all six tonsils are present. Proper tonsils are absent in the rat, and pigeon. In the rabbit, only the palatine tonsils can be noticed, whereas the pig does not present palatine tonsils. The paraepiglottic tonsils lack in the ox, horse, and dog. In addition, the dog and cat are devoid of the tubal tonsil and the tonsil of the soft palate.