Bone Perfusion Alterations in Chronic Kidney Disease

Indiana University-Purdue University Indianapolis (IUPUI)Patients with chronic kidney disease (CKD) are at an alarming risk of fracture and cardiovascular disease-associated mortality. There is a critical need to better understand the underlying mechanism driving altered cardiovascular and skeletal homeostasis, as well as any connection between the two. CKD has been shown to have negative effects on many vascular properties including endorgan perfusion. Surprisingly, exploration of skeletal perfusion and vasculature has not been undertaken in CKD. Alterations in bone perfusion are linked to dysregulation of bone remodeling and mass in multiple conditions. An understanding of the detrimental impact of CKD on bone perfusion is a crucial step in understanding bone disease in these patients. The goal of this series of studies was to test the global hypothesis that skeletal perfusion is altered in CKD and that alterations can be modulated through treatments that affect metabolic dysfunction. These studies utilized a rat model of CKD to conduct metabolic assessments, bone perfusion measurements, bone imaging studies, and isolated vessel reactivity experiments. Our results showed that animals with CKD had higher levels of parathyroid hormone (PTH), leading to substantial bone resorption. Bone perfusion measurements showed CKD-induced elevations in cortical bone perfusion with levels progressing alongside CKD severity. Conversely we show that marrow perfusion was lower in advanced CKD. PTH suppression therapy in animals with CKD resulted in the normalization of cortical bone perfusion and cortical bone mass, but did not normalize marrow bone perfusion. These results show a clear association between bone deterioration and altered bone perfusion in CKD. While the relationship of altered bone perfusion and bone deterioration in CKD necessitates further work, these results indicate that determining the mechanisms of bone perfusion alterations and whether they are drivers, propagators, or consequences of skeletal deterioration in CKD could help untangle a key player in CKD-induced bone alterations

What Animal Models Have Taught Us About the Safety and Efficacy of Bisphosphonates in Chronic Kidney Disease

Purpose of Review Bisphosphonates (BPs) have long been the gold-standard anti-remodeling treatment for numerous metabolic bone diseases. Since these drugs are excreted unmetabolized through the kidney, they are not recommended for individuals with compromised kidney function due to concerns of kidney and bone toxicity. The goal of this paper is to summarize the preclinical BP work in models of kidney disease with particular focus on the bone, kidney, and vasculature. Recent Findings Summative data exists showing positive effects on bone and vascular calcifications with minimal evidence for bone or kidney toxicity in animal models. Summary Preclinical data suggest it may be worthwhile to take a step back and reconsider the use of bisphosphonates to lessen skeletal/vascular complications associated with compromised kidney function

Chaos in Shear Flows

Almost 25 years ago Lorenz published his seminal study on the existence of a strange attractor in the phase space of a severely truncated model system arising from the hydrodynamical equations describing two-dimensional convection. Nearly a century ago Poincare published his famous treatise Les Methodes Noovelles de la Mecaniaue Celeste (1892) in which the possible complexity of behavior in nonintegrable, conservative systems was first envisioned. Both these works address an age old puzzle: How do apparently stochastic outputs arise from an entirely deterministic system subject to non-stochastic inputs

Measuring Topological Chaos

The orbits of fluid particles in two dimensions effectively act as topological obstacles to material lines. A spacetime plot of the orbits of such particles can be regarded as a braid whose properties reflect the underlying dynamics. For a chaotic flow, the braid generated by the motion of three or more fluid particles is computed. A ``braiding exponent'' is then defined to characterize the complexity of the braid. This exponent is proportional to the usual Lyapunov exponent of the flow, associated with separation of nearby trajectories. Measuring chaos in this manner has several advantages, especially from the experimental viewpoint, since neither nearby trajectories nor derivatives of the velocity field are needed.Comment: 4 pages, 6 figures. RevTeX 4 with PSFrag macro

Assessment of regional bone tissue perfusion in rats using fluorescent microspheres

Disturbances in bone blood flow have been shown to have deleterious effects on bone properties yet there remain many unanswered questions about skeletal perfusion in health and disease, partially due to the complexity of measurement methodologies. The goal of this study was use fluorescent microspheres in rats to assess regional bone perfusion by adapting mouse-specific fluorescent microsphere protocol. Ten fifteen-week old Sprague Dawley rats were injected with fluorescent microspheres either via cardiac injection (n = 5) or via tail vein injection (n = 5). Femora and tibiae were harvested and processed to determine tissue fluorescence density (TFD) which is proportional to the number of spheres trapped in the tissue capillaries. Right and left total femoral TFD (2.77 ± 0.38 and 2.70 ± 0.24, respectively) and right and left tibial TFD (1.11 ± 0.26 and 1.08 ± 0.34, respectively) displayed bilateral symmetry in flow when assessed in cardiac injected animals. Partitioning of the bone perfusion into three segments along the length of the bone showed the distal femur and proximal tibia received the greatest amount of perfusion within their respective bones. Tail vein injection resulted in unacceptably low TFD levels in the tibia from 4 of the 5 animals. In conclusion this report demonstrates the viability of cardiac injection of fluorescent microspheres to assess bone tissue perfusion in rats

Rain, power laws, and advection

Localized rain events have been found to follow power-law size and duration distributions over several decades, suggesting parallels between precipitation and seismic activity [O. Peters et al., PRL 88, 018701 (2002)]. Similar power laws are generated by treating rain as a passive tracer undergoing advection in a velocity field generated by a two-dimensional system of point vortices.Comment: 7 pages, 4 figure

Zoledronate treatment has different effects in mouse strains with contrasting baseline bone mechanical phenotypes

Aref, M. W., McNerny, E. M. B., Brown, D., Jepsen, K. J., & Allen, M. R. (2016). Zoledronate treatment has different effects in mouse strains with contrasting baseline bone mechanical phenotypes. Osteoporosis International : A Journal Established as Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 27(12), 3637–3643. https://doi.org/10.1007/s00198-016-3701-

Visualizing Structural Balance in Signed Networks

Network visualization has established as a key complement to network analysis since the large variety of existing network layouts are able to graphically highlight different properties of networks. However, signed networks, i.e., networks whose edges are labeled as friendly (positive) or antagonistic (negative), are target of few of such layouts and none, to our knowledge, is able to show structural balance, i.e., the tendency of cycles towards including an even number of negative edges, which is a well-known theory for studying friction and polarization. In this work we present Structural-balance-viz: a novel visualization method showing whether a connected signed network is balanced or not and, in the latter case, how close the network is to be balanced. Structural-balance-viz exploits spectral computations of the signed Laplacian matrix to place network's nodes in a Cartesian coordinate system resembling a balance (a scale). Moreover, it uses edge coloring and bundling to distinguish positive and negative interactions. The proposed visualization method has characteristics desirable in a variety of network analysis tasks: Structural-balance-viz is able to provide indications of balance/polarization of the whole network and of each node, to identify two factions of nodes on the basis of their polarization, and to show their cumulative characteristics. Moreover, the layout is reproducible and easy to compare. Structural-balance-viz is validated over synthetic-generated networks and applied to a real-world dataset about political debates confirming that it is able to provide meaningful interpretations