80 research outputs found
A Mathematical Model of Oxygen Transport in Skeletal Muscle During Hindlimb Unloading
During hindlimb unloading (HU) dramatic fluid shifts occur within minutes of the suspension, leading to a less precise matching of blood flow to O2 demands of skeletal muscle. Vascular resistance directs blood away from certain muscles, such as the soleus (SOL). The muscle volume gradually reduces in these muscles so that eventually the relative blood flow returns to normal. It is generally believed that muscle volume change is not due to O2 depletion, but a consequence of disuse. However, the volume of the unloaded rat muscle declines over the course of weeks, whereas the redistribution of blood flow occurs immediately. Using a Krogh Cylinder Model, the distribution of O2 was predicted in two skeletal muscles: SOL and gastrocnemius (GAS). Effects of the muscle blood flow, volume, capillary density, and O2 uptake, are included to calculate the pO2 at rest and after 10 min and 15 days of unloading. The model predicts that 32 percent of the SOL muscle tissue has a pO2 1.25 mm Hg within 10 min, whereas the GAS maintains normal O2 levels, and that equilibrium is reached only as the SOL muscle cells degenerate. The results provide evidence that there is an inadequate O2 supply to the mitochondria in the SOL muscle after 10 min HU
Frequency and Distribution of Microcalcifications in Vulnerable Plaque and Their Role in Fibrous Cap Rupture
The Glycocalyx and Its Role in Vascular Physiology and Vascular Related Diseases
Purpose—In 2007 the two senior authors wrote a review on the structure and function of the endothelial glycocalyx layer (Weinbaum in Annu Rev Biomed Eng 9:121–167, 2007). Since then there has been an explosion of interest in this hydrated gel-like structure that coats the luminal surface of endothelial cells that line our vasculature due to its important functions in (A) basic vascular physiology and (B) vascular related diseases. This review will highlight the major advances that have occurred since our 2007 paper.
Methods—A literature search mainly focusing on the role of the glycocalyx in the two major areas described above was performed using electronic databases.
Results—In part (A) of this review, the new formulation of the century old Starling principle, now referred to as the Michel–Weinbaum glycoclayx model or revised Starling hypothesis, is described including new subtleties and physiological ramifications. New insights into mechanotransduction and release of nitric oxide due to fluid shear stress sensed by the glycocalyx are elaborated. Major advances in understanding the organization and function of glycocalyx components, and new techniques for measuring both its thickness and spatio-chemical organization based on super resolution, stochastic optical reconstruction microscopy (STORM) are presented. As discussed in part (B) of this review, it is now recognized that artery wall stiffness associated with hypertension and aging induces glycocalyx degradation, endothelial dysfunction and vascular disease. In addition to atherosclerosis and cardiovascular diseases, the glycocalyx plays an important role in lifestyle related diseases (e.g., diabetes) and cancer. Infectious diseases including sepsis, Dengue, Zika and Corona viruses, and malaria also involve the glycocalyx. Because of increasing recognition of the role of the glycocalyx in a wide range of diseases, there has been a vigorous search for methods to protect the glycocalyx from degradation or to enhance its synthesis in disease environments.
Conclusion—As we have seen in this review, many important developments in our basic understanding of GCX structure, function and role in diseases have been described since the 2007 paper. The future is wide open for continued GCX research
Nanoanalytical analysis of bisphosphonate-driven alterations of microcalcifications using a 3D hydrogel system and in vivo mouse model
Vascular calcification predicts atherosclerotic plaque rupture and cardiovascular events. Retrospective studies of women taking bisphosphonates (BiPs), a proposed therapy for vascular calcification, showed that BiPs paradoxically increased morbidity in patients with prior acute cardiovascular events but decreased mortality in event-free patients. Calcifying extracellular vesicles (EVs), released by cells within atherosclerotic plaques, aggregate and nucleate calcification. We hypothesized that BiPs block EV aggregation and modify existing mineral growth, potentially altering microcalcification morphology and the risk of plaque rupture. Three-dimensional (3D) collagen hydrogels incubated with calcifying EVs were used to mimic fibrous cap calcification in vitro, while an ApoE−/− mouse was used as a model of atherosclerosis in vivo. EV aggregation and formation of stress-inducing microcalcifications was imaged via scanning electron microscopy (SEM) and atomic force microscopy (AFM). In both models, BiP (ibandronate) treatment resulted in time-dependent changes in microcalcification size and mineral morphology, dependent on whether BiP treatment was initiated before or after the expected onset of microcalcification formation. Following BiP treatment at any time, microcalcifications formed in vitro were predicted to have an associated threefold decrease in fibrous cap tensile stress compared to untreated controls, estimated using finite element analysis (FEA). These findings support our hypothesis that BiPs alter EV-driven calcification. The study also confirmed that our 3D hydrogel is a viable platform to study EVmediated mineral nucleation and evaluate potential therapies for cardiovascular calcification
Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142904/1/hep29800.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142904/2/hep29800_am.pd
Genesis and growth of extracellular vesicle-derived microcalcification in atherosclerotic plaques
Clinical evidence links arterial calcification and cardiovascular risk. Finite-element modelling of the stress distribution within atherosclerotic plaques has suggested that subcellular microcalcifications in the fibrous cap may promote material failure of the plaque, but that large calcifications can stabilize it. Yet the physicochemical mechanisms underlying such mineral formation and growth in atheromata remain unknown. Here, by using three-dimensional collagen hydrogels that mimic structural features of the atherosclerotic fibrous cap, and high-resolution microscopic and spectroscopic analyses of both the hydrogels and of calcified human plaques, we demonstrate that calcific mineral formation and maturation results from a series of events involving the aggregation of calcifying extracellular vesicles, and the formation of microcalcifications and ultimately large calcification zones. We also show that calcification morphology and the plaque’s collagen content – two determinants of atherosclerotic plaque stability - are interlinked
Natural convection in a horizontal circular cylinder
In this paper we examine the steady, two-dimensional convective motion which occurs in a horizontal circular cylinder whose wall is non-uniformly heated. One observes several qualitatively different physical phenomena depending on the wall temperature distribution and the value of the Rayleigh number. The low-Rayleigh-number behaviour for the single convective cell heated from below is related to the classical Rayleigh stability problem. The critical Rayleigh number for the single circular cell is approximately five times the value for Rayleigh's multi-celluar configuration. The flow which exhibits a nearly parabolic velocity profile near the critical Rayleigh number, gradually changes to a rigidly-rotating-core behaviour as the Rayleigh number increases. The speed of core rotation is a function of the Prandtl number, whereas the boundary-layer thickness is primarily a function of the Rayleigh number. When the heating is from side to side, the solution shows that as the Rayleigh number increases the core motion is progressively arrested leaving a narrow circulating band of fluid adjacent to the wall. An oblique heating produces a hybrid phenomenon, a low-Rayleigh-number behaviour which is characteristic of the sideways heating case and a high-Rayleigh-number interior motion characteristic of the bottom heating case. To determine the core motion in the high-Rayleigh-number limit, Batchelor's work concerning the uniqueness of incompressible, exactly steady, closed streamline flows with small viscosity is extended to include flows with small thermal conductivity
Fulfilling the Dream: The Importance of Doing What You Believe and Being Taken Seriously
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