Category:
Bunion; Basic Sciences/Biologics
Introduction/Purpose:
It is generally accepted that failure of the medial supporting soft tissue structure of the metatarsophalangeal joint plays an ...important role in the development of hallux valgus. The metatarsosesamoid ligament (MSL), a component of the medial soft tissue, is an important structure that connects the metatarsal head and the sesamoid complex. The sesamoid complex works as a dynamic stabilizer of the metatarsal head. We hypothesized that the failure of the medial MSL causes instability of the first metatarsal bone, which leads to hallux valgus deformities. Therefore, the present study aimed to describe the detailed structure and degenerative findings of MSL and to clarify the mechanical stress of the MSL enthesis, considering the mechanism of failure of the medial supporting soft tissue structure.
Methods:
The first metatarsal heads and sesamoid bones with soft tissue were collected from twelve cadavers. Serial 4-μm thick section4-μm intervals and stained with toluidine blue (Fig. 1a). We described the detailed histological structures and degenerative findings of MSL. In addition, morphometric comparisons were made between the medial and lateral MSL entheses at the metatarsal head to evaluate the mechanical stress they. First, we measured the thickness of the uncalcified fibrocartilage (UF thickness) following a protocol adopted previously (Fig. 1b). Second, the degree of irregularity of the interface between the zones of calcified fibrocartilage and bone (CFB) at each enthesis was assessed as the ratio between the lengths of the CFB and the enthesis (CFB/ E ratio) (Fig. 1c). The differences in these parameters were evaluated using the paired T test and Wilcoxon signed-rank test (P < 0.05).
Results:
We identified that the MSL entheses were fibrocartilaginous entheses, which consisted of four tissue zones. The region in which the MSL wraps around the articular surface of the metatarsal head contains a metachromatic area accompanied by fibrocartilage cells at the deep surface of the MSL, called the sesamoid fibrocartilage. At the MSL enthesis, pathological findings indicating enthesopathy were observed. One specimen showed the tear of the MSL at the wrap around region. The MSL enthesis tear was observed in two specimens with hallux valgus. Both UF thickness (P = 0.12, effect size r = 0.89) and CFB/E ratio (P = 0.17, effect size d = 0.35) were significantly greater in the medial MSL enthesis than those in the lateral MSL enthesis.
Conclusion:
In the present study, the MSL showed enthesis protecting structures such as enthesis fibrocartilage which contributes to dissipating bending forces during insertional angle change, complexed CFB interface which guards an enthesis against shearing forces and wrap around region which contributes to dissipating the shearing force to the enthesis. However, the medial MSL subject to the greater forces and the degenerative findings of enthesopathy were observed. On top of that, all four hallux valgus specimens with sesamoid complex dislocation showed MSL enthesis tear. Enthesopathy, particularly at the medial MSL, may be the cause of hallux valgus.
Abstract
INTRODUCTION
Brain arteriovenous malformations (bAVMs) are a rupture-prone tangle of blood vessels with direct shunting between arterial and venous circulations. The mechanisms contributing ...to bAVM pathogenesis in sporadic lesions remains elusive. Studies have focused on endothelial cells and the contributions of other cell types have yet to be studied. Pericytes are multi-functional cells which regulate brain angiogenesis and vascular stability. Here, we analyze the abundance of brain pericytes and their association with vascular changes in human bAVMs
METHODS
bAVMs and non-vascular lesion epilepsy tissue were surgically resected. Immunofluorescent staining was performed to quantify pericytes (platelet derived growth factor receptor beta (PDGFRbeta) and N-aminopeptidase (CD13)) and hemoglobin. Hemosiderin deposits were quantified with Prussian blue staining. Syngo-iFlow processing was utilized to measure blood flow on pre-intervention angiograms.
RESULTS
>Immunofluorescent analysis demonstrated a 68% reduction in vascular pericyte number in bAVMs (P < 0.01). Analysis demonstrated 52% and 50% reduction in the vascular surface area covered by CD13- and PDGFRbeta-positive pericyte cell processes, respectively, in bAVMs (P < 0.01). Reductions in pericyte coverage were greatest in ruptured bAVMs (P < 0.05), and correlated negatively with microhemorrhage-derived extravascular hemoglobin in unruptured cases (CD13: r = −0.93, P < 0.01; PDGFRbeta: r = −0.87, P < 0.01). A similar negative correlation was observed with pericyte coverage and Prussian-blue positive hemosiderin deposits. Pericyte coverage correlated positively with mean transit time of blood flow through the bAVM nidus (CD13: r = 0.60, P < 0.05; PDGFRbeta: r = 0.63, P < 0.05).
CONCLUSION
Pericytes are reduced in sporadic bAVMs and are lowest in cases with prior rupture or with greatest mircohemorrhage burden. Pericytes also correlate with rate of blood flow through the bAVM nidus. This suggests that pericytes are associated with and may contribute to vascular fragility and hemodynamic changes in bAVMs Future studies are needed to better characterize the role of pericytes in AVM pathogenesis.
An abstract of a study by Richman et al to determine the pathogenesis of anti-muscle-specific kinase (MuSK) myasthenia is presented. Animals immunized with 100 pg of MuSK 60 deve1oped severe ...progressive weakness starting at day 16, with 100% mortality by day 27. The weakness was associated with high MuSK antibody titers, weight loss, axial muscle wasting, and decrementing compound muscle action potentials. Light and electron microscopy demonstrated fragmented NMJs with varying degrees of postsynaptic muscle end plate destruction along with abnormal nerve terminals, lack of registration between end plates and nerve terminals, local axon sprouting. and extrajunctional dispersion of cholinesterase activity. They conclude that their findings support the role of MuSK antibodies in the human disease, demonstrate the role of MuSK not only in the developrnent of the NMJ but also in the maintenance of the mature synapse, and demonstrate involvement of this disease in both presynaptic and postsynaptic components of the NMJ.
Immune Thrombocytopenia Abadi Uri; Yarchovsky-Dolberg Osnat; Ellis, Martin H
Clinical and applied thrombosis/hemostasis,
07/2015, Letnik:
21, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Immune thrombocytopenia (ITP) is a rare autoimmune disorder with an incidence of 3 to 5 per 100 000 individuals. In children, the disease is self-limited and is most commonly virus related (acute ...ITP) whereas in adults, the disease is typically chronic. The age distribution of adult ITP displays 2 peaks; the first in younger adults aged 18 to 40 with a female predominance and the second in people aged older than 60 with men and women affected equally. Our approach to ITP has evolved over the past several years: there has been a change in nomenclature and ITP now denotes “immune thrombocytopenia” (the “I” no longer denoting “idiopathic”) and “purpura” no longer features in the name of the disease; new insights into the pathogenesis of ITP have revealed the importance of impaired megakaryocytopoiesis in the condition; underlying mechanisms of secondary ITP have been elucidated and finally novel thrombopoietic agents have been shown to be effective in the treatment of ITP in randomized clinical trials. In this article, we review important recent advances in the pathogenesis and treatment of ITP.
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