Kidney damage in extracorporeal shock wave lithotripsy: a numerical approach for different shock profiles

In shock-wave lithotripsy—a medical procedure to fragment kidney stones—the patient is subjected to hypersonic waves focused at the kidney stone. Although this procedure is widely applied, the physics behind this medical treatment, in particular the question of how the injuries to the surrounding kidney tissue arise, is still under investigation. To contribute to the solution of this problem, two- and three-dimensional numerical simulations of a human kidney under shock-wave loading are presented. For this purpose a constitutive model of the bio-mechanical system kidney is introduced, which is able to map large visco-elastic deformations and, in particular, material damage. The specific phenomena of cavitation induced oscillating bubbles is modeled here as an evolution of spherical pores within the soft kidney tissue. By means of large scale finite element simulations, we study the shock-wave propagation into the kidney tissue, adapt unknown material parameters and analyze the resulting stress states. The simulations predict localized damage in the human kidney in the same regions as observed in animal experiments. Furthermore, the numerical results suggest that in first instance the pressure amplitude of the shock wave impulse (and not so much its exact time-pressure profile) is responsible for damaging the kidney tissue.     

On the propagation of a wave front in viscoelastic arteries

In formulating a mathematical model of the arterial system, the one-dimensional flow approximation yields realistic pressure and flow pulses in the proximal as well as in the distal regions of a simulated arterial conduit, provided that the viscoelastic damping induced by the vessel wall is properly taken into account. Models which are based on a purely elastic formulation of the arterial wall properties are known to produce shocklike transitions in the propagating pulses which are not observed in man under physiological conditions. The viscoelastic damping characteristics are such that they are expected to reduce the tendency of shock formation in the model. In order to analyze this phenomenon, the propagation of first and second-order pressure waves is calculated with the aid of a wave front expansion, and criteria for the formation of shocks are derived. The application of the results to the human arterial system show that shock waves are not to be expected under normal conditions, while in case of a pathologically increased pressure rise at the root of the aorta, shocklike transitions may develop in the periphery. In particular, it is shown that second-order waves never lead to shock formation in finite time for the class of initial conditions and mechanical wave guides which are of interest in the mammalian circulation.     

Melanin Granule Models for the Processes of Laser-Induced Thermal Damage in Pigmented Retinal Tissues. I. Modeling of Laser-Induced Heating of Melanosomes and Selective Thermal Processes in Retinal Tissues

The computer modeling was applied for investigation of the processes of laser-induced tissue damage. The melanin granule models for the processes of laser-induced thermal damage and the results of computer modeling of the optical, thermophysical, and thermochemical processes during selective laser interaction with melanoprotein granules (melanosomes) in retinal pigment epithelium are presented in this paper. Physical-mathematical model and system of equations are formulated which describe thermal interaction processes for “short” laser pulses of duration t _p<10⁻⁶ s and for “ long’ pulses of duration t _p10⁻⁶ s. Results of numerical simulation of the processes give the space–time distributions of temperature and degrees of thermodenaturation of the protein molecules inside and around melanosomes and in the volume of irradiated tissues. Energy absorption, heat transfer and thermochemical (thermodenaturation, coagulation) processes occurring during the interaction of laser pulses with pigmented spherical and spheroidal granules in heterogeneous tissues are theoretically investigated. The possibility for selective interaction of short laser pulses with pigmented granules is discussed which results in the formation of denaturation microregions inside and near the pigmented granules (granular thermodenaturation) without origination of a continuous macroscopic thermodenaturation lesion in tissue. Analytical model of heating of single spherical and spheroidal granule under laser pulse is presented. Simple equations for time dependencies of particle temperature are obtained. The presented results are of essential interest for laser applications in and can be used for investigation of laser interaction with pigmented tissues in different fields of laser medicine.     

Finite element modelling of radial shock wave therapy for chronic plantar fasciitis

Therapeutic use of high-amplitude pressure waves, or shock wave therapy (SWT), is emerging as a popular method for treating musculoskeletal disorders. However, the mechanism(s) through which this technique promotes healing are unclear. Finite element models of a shock wave source and the foot were constructed to gain a better understanding of the mechanical stimuli that SWT produces in the context of plantar fasciitis treatment. The model of the shock wave source was based on the geometry of an actual radial shock wave device, in which pressure waves are generated through the collision of two metallic objects: a projectile and an applicator. The foot model was based on the geometry reconstructed from magnetic resonance images of a volunteer and it comprised bones, cartilage, soft tissue, plantar fascia, and Achilles tendon. Dynamic simulations were conducted of a single and of two successive shock wave pulses administered to the foot. The collision between the projectile and the applicator resulted in a stress wave in the applicator. This wave was transmitted into the soft tissue in the form of compression–rarefaction pressure waves with an amplitude of the order of several MPa. The negative pressure at the plantar fascia reached values of over 1.5 MPa, which could be sufficient to generate cavitation in the tissue. The results also show that multiple shock wave pulses may have a cumulative effect in terms of strain energy accumulation in the foot.     

Amyloid-β Decreases Nitric Oxide Production in Cultured Retinal Neurons: A Possible Mechanism for Synaptic Dysfunction in Alzheimer’s Disease?

The neurotoxicity of the amyloid-β peptide (Aβ) appears to be, at least in part, related to pathological activation of glutamate receptors by Aβ aggregates. However, the downstream signaling pathways leading to neurodegeneration are still incompletely understood. Hyperactivation of nitric oxide synthase (NOS) and increased nitric oxide (NO) production have been implicated in excitotoxic neuronal damage caused by overactivation of glutamate receptors, and it has been suggested that increased NO levels might also play a role in neurotoxicity in Alzheimer’s disease. We have examined the effect of blockade of NO production on the neurotoxicity instigated by Aβ₄₂ and by elevated concentrations of glutamate in chick embryo retinal neurons in culture. Results showed that l-nitroarginine methyl ester, a potent inhibitor of all NOS isoforms, had no protective effect against neuronal death induced by either Aβ₄₂ (20 μM) or glutamate (1 mM). Surprisingly, at short incubation times both Aβ and glutamate decreased NO production in retinal neuronal cultures in the absence of neuronal death. Thus, excitotoxic insults induced by Aβ and glutamate cause inhibition rather than activation of NO synthase in retinal neurons, suggesting that cell death induced by Aβ or glutamate is not related to increased NO production. On the other hand, considering the role of NO in long term potentiation and synaptic plasticity, the decrease in NO levels instigated by Aβ and glutamate suggests a possible mechanism leading to synaptic failure in AD.     

Real‐time monitoring of incision profile during laser surgery using shock wave detection

Lack of sensory feedback during laser surgery prevents surgeons from discerning the exact location of the incision, which increases duration and complexity of the treatment. In this study we demonstrate a new method for monitoring of laser ablation procedures. Real‐time tracking of the exact three dimensional (3D) lesion profile is accomplished by detection of shock waves emanating from the ablation spot and subsequent reconstruction of the incision location using time‐of‐flight data obtained from multiple acoustic detectors. Here, incisions of up to 9 mm in depth, created by pulsed laser ablation of fresh bovine tissue samples, were successfully monitored in real time. It was further observed that, by utilizing as little as 12 detection elements, the incision profile can be characterized with accuracy below 0.5 mm in all three dimensions and in good agreement with histological examinations. The proposed method holds therefore promise for delivering high precision real‐time feedback during laser surgeries. (© 2013 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)     

Extension of Bacillus endospore gas dynamic heating studies to multiple species and test conditions

Aims: Shock wave–induced damage to a variety of Bacillus endospore species is studied for a wide range of postshock temperatures and test times in oxidative and non‐oxidative gas environments. Methods and Results: Bacillus atrophaeus and Bacillus subtilis endospores are nebulized into an aqueous aerosol, loaded into the Stanford aerosol shock tube (SAST) and subjected to shock waves of controlled strength. Endospores experience uniform test temperatures between 500 and 1000 K and pressures ranging from 2 to 7 atm, for either a short test time (～2·5 ms) or a relatively long test time (～45 ms). During this process, the bioaerosol is observed using in situ laser absorption and scattering diagnostics. Additionally, shock‐treated samples are extracted for ex situ analysis including viability plating and flow cytometry. For short test times, results are consistent with previous studies; all endospore species begin to lose the ability to form colonies when shock‐heated to temperatures above 500 K, while significant breakdown in morphology is observed for postshock temperatures above 700 K. Oxidative bath gases did not affect viability losses or morphological breakdown rates. Experiments with extended postshock test time showed increased viability loss with minimal morphological damage for shocks between 600 and 700 K. Conclusions: Genetic differences between B. subtilis and B. atrophaeus endospores do not confer noticeable gains in resistance to shock heating. Oxidative environments do not exacerbate shock‐induced damage to endospores. Extended test time experiments reinforce our hypothesis that a temperature/time‐dependent inactivation mechanism that does not involve morphological breakdown exists at low‐to‐moderate postshock temperatures. Significance and Impact of the Study: The methodology and experiments described in this paper extend the study of the interactions of endospores with shock/blast waves to new species and environmental conditions.     

A new model for laser-induced thermal damage in the retina

We describe a new model for laser-induced retinal damage. Our treatment is prompted by the failure of the traditional approach to accurately describe the image size dependence of laser-induced retinal injuries and by a recently reported study which demonstrated that laser injuries to the retina might not appear for up to 48 h post exposure. We propose that at threshold a short-duration, laser-induced, temperature rise melts the membrane of the melanosomes found in the pigmented retinal epithelial cells. This results in the generation of free radicals which initiate a slow chain reaction. If more than a critical number of radicals are generated then cell death may occur at a time much later than the return of the retina to body temperature. We show that the equations consequent upon this mechanism result in a good fit to the recent image size data although more detailed experimental data for rate constants of elementary reactions is still required. This paper contributes to the current understanding of damage mechanisms in the retina and may facilitate the development of new treatments to mitigate laser injuries to the eye. The work will also help minimize the need for further animal experimentation to set laser eye safety standards. Unemployed; no address available.     

Cytoplasmic molecular delivery with shock waves: importance of impulse

Cell permeabilization using shock waves may be a way of introducing macromolecules and small polar molecules into the cytoplasm, and may have applications in gene therapy and anticancer drug delivery. The pressure profile of a shock wave indicates its energy content, and shock-wave propagation in tissue is associated with cellular displacement, leading to the development of cell deformation. In the present study, three different shock-wave sources were investigated; argon fluoride excimer laser, ruby laser, and shock tube. The duration of the pressure pulse of the shock tube was 100 times longer than the lasers. The uptake of two fluorophores, calcein (molecular weight: 622) and fluorescein isothiocyanate-dextran (molecular weight: 71,600), into HL-60 human promyelocytic leukemia cells was investigated. The intracellular fluorescence was measured by a spectrofluorometer, and the cells were examined by confocal fluorescence microscopy. A single shock wave generated by the shock tube delivered both fluorophores into approximately 50% of the cells (p < 0.01), whereas shock waves from the lasers did not. The cell survival fraction was >0.95. Confocal microscopy showed that, in the case of calcein, there was a uniform fluorescence throughout the cell, whereas, in the case of FITC-dextran, the fluorescence was sometimes in the nucleus and at other times not. We conclude that the impulse of the shock wave (i.e., the pressure integrated over time), rather than the peak pressure, was a dominant factor for causing fluorophore uptake into living cells, and that shock waves might have changed the permeability of the nuclear membrane and transferred molecules directly into the nucleus.     

Modeling the pre- and post-synaptic components involved in the synaptic modification between cones and horizontal cells in carp retina

In retinal synapses between cones and luminosity type horizontal cells (LHC), it was previously found in this laboratory that repetitive red flashes progressively strengthened the LHC’s response to red flash, whereas weakened the LHC’s response to green flash; repetitive green flash remarkably depressed the LHC’s red response, but caused little changes in the cell’s green response. However, the detailed mechanisms underlying these phenomena are not entirely clear. In the present study, based on an ion-channel model described mainly in the form of Hodgkin–Huxley equations, possible mechanisms of the short-term synaptic modification are investigated. The simulation results suggest that: (1) the auto-enhancement effect might be induced by the Ca²⁺-dependent process on the post-synaptic AMPA receptors, which could lead to changes of the ionic channel’s properties; (2) the asymmetric response to red- and green-flashes and the mutual-chromatic suppression effects might be attributed to the regulatory effects on the presynaptic glutamate release.     

Dose‐dependent study of effects of 532‐nm continuous wave laser on rat skin: A mechanistic insight

Visible lasers emitting in the green spectral region are being routinely employed in various medical and defense fields namely treatment of pigmented lesions, tattoo inks, port wine stains, dazzling the target or mob dispersal. Despite their increasing applications, lasers also tend to pose occupational hazards to operators, ancillary personnel, individuals undergoing laser therapies. This study was aimed at investigating the effects of different doses of 532‐nm continuous wave laser on rat skin. The present study demonstrated that higher fluences of 532‐nm continuous wave (CW) laser induces significant tissue damage through induction of tumor necrosis factor‐α, cyclooxygenase‐2, tumor protein (p53), PARP 1, caspase3 which in turn leads to tissue damage and cell death. Furthermore, level of heat shock proteins, pAkt were found up‐regulated as a cope up response to laser‐induced stress. On the basis of the findings, irradiation with 532‐nm CW laser up to 2.5 J/cm² was found within the safe exposure limits. Thus, it is probably the first attempt to demonstrate the tissue damage induced by 532‐nm CW laser on skin, which may help in choosing safe laser dose for certain skin‐based applications and evolving methods to ameliorate laser‐inflicted injuries.     

Global and Ocular Hypothermic Preconditioning Protect the Rat Retina from Ischemic Damage

Retinal ischemia could provoke blindness. At present, there is no effective treatment against retinal ischemic damage. Strong evidence supports that glutamate is implicated in retinal ischemic damage. We investigated whether a brief period of global or ocular hypothermia applied 24 h before ischemia (i.e. hypothermic preconditioning, HPC) protects the retina from ischemia/reperfusion damage, and the involvement of glutamate in the retinal protection induced by HPC. For this purpose, ischemia was induced by increasing intraocular pressure to 120 mm Hg for 40 min. One day before ischemia, animals were submitted to global or ocular hypothermia (33°C and 32°C for 20 min, respectively) and fourteen days after ischemia, animals were subjected to electroretinography and histological analysis. Global or ocular HPC afforded significant functional (electroretinographic) protection in eyes exposed to ischemia/reperfusion injury. A marked alteration of the retinal structure and a decrease in retinal ganglion cell number were observed in ischemic retinas, whereas global or ocular HPC significantly preserved retinal structure and ganglion cell count. Three days after ischemia, a significant decrease in retinal glutamate uptake and glutamine synthetase activity was observed, whereas ocular HPC prevented the effect of ischemia on these parameters. The intravitreal injection of supraphysiological levels of glutamate induced alterations in retinal function and histology which were significantly prevented by ocular HPC. These results support that global or ocular HPC significantly protected retinal function and histology from ischemia/reperfusion injury, probably through a glutamate-dependent mechanism.     

Numerical simulation of blood and interstitial flow through a solid tumor

A theoretical framework is presented for describing blood flow through the irregular vasculature of a solid tumor. The tumor capillary bed is modeled as a capillary tree of bifurcating segments whose geometrical construction involves deterministic and random parameters. Blood flow along the individual capillaries accounts for plasma leakage through the capillary walls due to the transmural pressure according to Sterling’s law. The extravasation flow into the interstitium is described by Darcy’s law for a biological porous medium. The pressure field developing in the interstitium is computed by solving Laplace’s equation subject to derived boundary conditions at the capillary vessel walls. Given the arterial, venous, and tumor surface pressures, the problem is formulated as a coupled system of integral and differential equations arising from the interstitium and capillary flow transport equations. Numerical discretization yields a system of linear algebraic equations for the interstitial and capillary segment pressures whose solution is found by iterative methods. Results of numerical computations document the effect of the interstitial hydraulic and vascular permeability on the fractional plasma leakage. Given the material properties, the fractional leakage reaches a maximum at a particular grade of the bifurcating vascular tree.     

Colliding saccades evoked by frontal eye field stimulation: artifact or evidence for an oculomotor compensatory mechanism underlying double-step saccades?

 What happens when the goal is changed before the movement is executed? Both the double-step and colliding saccade paradigms address this issue as they introduce a discrepancy between the retinal images of targets in space and the commands generated by the oculomotor system necessary to attain those targets. To maintain spatial accuracy under such conditions, transformations must update ‘retinal error’ as eye position changes, and must also accommodate neural transmission delays in the system so that retinal and eye position information are temporally aligned. Different hypotheses have been suggested to account for these phenomena, based on observations of dissociable cortical and subcortical compensatory mechanisms. We now demonstrate how a single compensatory mechanism can be invoked to explain both double-step and colliding saccade paradigm results, based on the use of a damped signal of change in position that is used in both cases to update retinal error and, thereby, account for intervening movements. We conclude that the collision effect is not an artifact, but instead reveals a compensatory mechanism for saccades whose targets appear near the onset of a preceding saccade. Received: 14 February 1996/Accepted in revised form: 17 September 1996     

Shock wave treatment in medicine

Extracorporeal shock wave therapy in orthopedics and traumatology is still a young therapy method. Since the last few years the development of shock wave therapy has progressed rapidly. Shock waves have changed the treatment of urolithiasis substantially. Today shock waves are the first choice to treat kidney and urethral stones. Urology has long been the only medical field for shock waves in medicine. Meanwhile shock waves have been used in orthopedics and traumatology to treat insertion tendinitis, avascular necrosis of the head of femur and other necrotic bone alterations. Another field of shock wave application is the treatment of tendons, ligaments and bones on horses in veterinary medicine. In the present paper we discuss the basic theory and application of shock waves and its history in medicine. The idea behind using shock wave therapy for orthopedic diseases is the stimulation of healing in tendons, surrounding tissue and bones. This is a completely different approach compared to urology where shock waves are used for disintegration     

Bacillus endospore resistance to gas dynamic heating

Aim: To develop a novel laboratory procedure for the study of shock wave‐induced damage to Bacillus endospores. Methods and Results: Bacillus atrophaeus endospores are nebulized into an aerosol, loaded into the stanford aerosol shock tube and subjected to shock waves of controlled strength. Endospores experience uniform test temperatures between 500 and 1000 K and pressures ranging from 2 to 7 atm, for a relatively short time (2–3 ms). During this process, the bioaerosol is observed using in situ laser absorption and scattering diagnostics. Additionally, shock‐treated samples are extracted for ex situ analysis including viability plating, flow cytometry and SEM imaging. Measurements indicate that endospores lose the ability to form colonies when heated to test temperatures above 500 K while significant breakdown in morphology is observed at test temperatures above 750 K. Conclusion: These results demonstrate the disruption of essential biochemical pathways or biomolecules prior to the onset of significant endospore morphological deterioration. Significance and Impact of the Study: This novel laboratory approach to study the interaction of endospores with shock waves provides an experimental means to investigate the mechanisms of endospore resistance to rapid heating. In addition, this methodology allows for the direct simulation of a blast wave–bioaerosol interaction in an atmospheric environment.     

Pressure wave propagation in fluid-filled co-axial elastic tubes. Part 1: Basic theory

Our work is motivated by ideas about the pathogenesis of syringomyelia. This is a serious disease characterized by the appearance of longitudinal cavities within the spinal cord. Its causes are unknown, but pressure propagation is probably implicated. We have developed an inviscid theory for the propagation of pressure waves in co-axial, fluid-filled, elastic tubes. This is intended as a simple model of the intraspinal cerebrospinal-fluid system. Our approach is based on the classic theory for the propagation of longitudinal waves in single, fluid-filled, elastic tubes. We show that for small-amplitude waves the governing equations reduce to the classic wave equation. The wave speed is found to be a strong function of the ratio of the tubes' cross-sectional areas. It is found that the leading edge of a transmural pressure pulse tends to generate compressive waves with converging wave fronts. Consequently, the leading edge of the pressure pulse steepens to form a shock-like elastic jump. A weakly nonlinear theory is developed for such an elastic jump.     

Modelling Dictyostelium discoideum morphogenesis: the culmination

The culmination of the morphogenesis of the cellular slime mould Dictyostelium discoideum involves complex cell movements which transform a mound of cells into a globule of spores on a slender stalk. We show that cyclic AMP signalling and differential adhesion, combined with cell differentiation and slime production, are sufficient to produce the morphogenetic cell movements which lead to culmination. We have simulated the process of culmination using a hybrid cellular automata/partial differential equation model. With our model we have been able to reproduce the main features that occur during culmination, namely the straight downward elongation of the stalk, its anchoring to the substratum and the formation of the long thin stalk topped by the spore head. We conclude that the cyclic AMP signalling system is responsible for the elongation and anchoring of the stalk, but in a roundabout way: pressure waves that are induced by the chemotaxis towards cyclic AMP squeeze the stalk through the cell mass. This mechanism forces the stalk to elongate precisely in the direction opposite to that of the chemotactically moving cells. The process turns out to be ‘guided’ by inactive ‘pathfinder’ cells, which form the tip of the stalk. We show that the entire development is enacted by means of the aforementioned building blocks. This means that no global gradients or different modes of chemotaxis are needed to complete the culmination. MPEG movies of the simulations are available on-line: http://www-binf.bio. uu.nl/stan/bmb.