Search

A cultured network of neurons coupled with a multi-electrode-array (MEA) recording system has been a useful platform for investigating various issues in neuroscience and engineering. The neural activity supported by the system can be sensitive to environmental fluctuations, for example, in the medium’s nutrient composition, ph, and temperature, and to mechanical disturbances, yet this issue has not been the subject. Especially, a normal practice in maintaining neuronal cell cultures involves an intermittent sequence of medium exchanges, typically at a time interval of a few days, and one such sudden medium exchange is unavoidably accompanied by many unintended disturbances. Here, based on a quantitative time-series analysis of synchronized bursting events, we explicitly demonstrate that such a medium exchange can, indeed, bring a huge change in the existing neural activity. Subsequently, we develop a medium perfusion-stirring system and an ideal protocol that can be used in conjunction with a MEA recording system, providing long-term stability. Specifically, we systematically evaluate the effects of medium stirring and perfusion rates. Unexpectedly, even some vigorous mechanical agitations do not have any impacts on neural activity. On the other hand, too much replenishment (e.g., 1.8 ml/day for a 1.8-ml dish) of neurobasal medium results in an excitotoxicity.

Purpose – The purpose of this paper is to present the computational model of the neonate’s brain cooling process. The main aim of the analysis is to tune the developed computational model, make it convergent and representing the hypothermia therapy reasonably. To find the appropriate model parameters the trial of an inverse analysis, based on the standard least-square method, is performed. Having partially validated model the number of numerical simulations are carried out to compare their results with measurements made during real therapy. Design Methodology Approach – The geometrical model of the newborn’s body is built using MRI and CT scans utilizing Mimics software and the Design Modeler while Ansys Fluent with its User Defined Function capability was used to implement the whole model and to carry out simulations. To model the bioheat transfer the Pennes bioheat equation is applied. In the mathematical model blood perfusion rate, metabolic heat generation rate as well as the arterial blood temperatur...

The influence of perfusion rate at the early phase of continuous cultivation on growth characteristics of CHO cells produ cing the therapeutic IgG1 and on the glycan profile of the produced MAb has been examined. It was established that non-optimal perfusion acceleration values caused some deviations from the normal transition of the cell culture to a steady-state phase of the process. For example, an excessive acceleration rate resulted in exceeding the maximum cell concentration that can be supported by cell culture medium. The cell growth was therefore limited and their viability dramatically decreased. The further recovery of growth and viability took a few days and reduced the economic efficiency of the process. Too low perfusion acceleration rate caused metabolic modifications in cell culture that affected its specific productivity and the quality of the synthesized protein. In particular, we observed the decrease in the target MAb fucosylation that could have a negative effect on the protein safety profile. In addition, the proliferation rate slowed down and cell volume increased by 2-2.5 times

This study aimed to simulate heat transfer in thermal equilibrium in the canine knee joint. We analyzed the impact of different values of blood perfusion available in the literature and considered blood perfusion rates. The geometric models of canine knee joints were created from a photographic record of a cross section of an anatomical part. Two geometric models were developed: one without the epidermis and one with the epidermis. A heat diffusion equation was used to model the heat transfer phenomenon. Numerical simulations of the canine knee in a thermal neutrality condition were performed using the ANSYS-CFX® program. The simulation results were compared with experimental in vivo data. The smaller percentage differences between the experimental and simulated in vivo results were found in simulations that used the blood flow rate as a function of temperature. The computer simulation proved to be a good alternative to evaluate the temperature of biological tissues.

Background & Aim The FDA approval of Novartis‘ Kymriah and Gilead‘s Yescarta chimeric antigen receptors (CAR)-T cell products in 2017 was a landmark announcement for the cellular immunotherapy field. But despite the excitement, manufacturing of these cell-based therapeutics still remains challenging and expensive. Whereas commercial cell therapy production requires robust and consistent manufacturing platforms, many processes are still highly variable and consist of manual handling steps. Rocking motion (RM) bioreactors are an attractive tool for the expansion of sensitive cells such as CAR-T cells, allowing for automated process control and reducing costs connected to traditional manual process steps. In this work, we compare T cell expansion in a RM bioreactor to classical, static cultures. Furthermore, we aim to improve culture productivity by optimized perfusion feeding in the RM bioreactor. Methods, Results & Conclusion Using human primary T cells enriched from cryopreserved PBMC from healthy donors as a model, we performed T cell expansion in static bags in a CO2 incubator in comparison to expansion in the BIOSTAT® RM TX using Flexsafe® RM TX bags. Keeping other culture parameters such as cell seeding density, medium and feeding constant, we evaluated cell growth, viability and T cell surface markers. In a second step, bioreactor cultures were further optimized by improved perfusion feeding based on glucose and lactate measurements. Our data show that expansion in a rocking motion bioreactor yields comparable or even higher cell growth than expansion in static cultures. Furthermore, in a simple approach based on measurements of glucose and lactate, bioreactor productivity was increased by using an improved perfusion feeding regime, resulting in cell concentrations of almost 5 × 107 c/ml. Further optimization of the expansion process and bioreactor productivity is envisioned by improving the feeding strategy. Based on spent medium analysis, we expect to reduce the perfusion rate and replenish depleted components with bolus additions of those components. In conclusion, RM bioreactors are promising platforms for cell therapy manufacturing processes. The BIOSTAT® RM TX platform allows for incorporation of online monitoring and process automation, thereby reducing labor and COG for manufacturing of commercial cell therapy products.

This paper introduces a non-invasive, contrast-enhanced ultrasound (CEUS) infusion method to quantify the health of viable donor livers. The method uses the infusion of microbubbles and their destruction and subsequent replenishment to measure the perfusion rate in the liver microvasculature. The proposed method improves on the previous parameter extraction approaches applied to the flash-replenishment technique by addressing the effects of the microbubble mixing within the perfusate bath and destruction rate. By doing so, the tissue perfusion rate can be extracted from the data even though the microbubble concentration is not constant throughout image acquisition. The measured changes in the tissue perfusion rate showed that CEUS infusion is a viable biomarker for assessing liver health.

Proliferation characteristics of CHO-K1 cells were investigated under a variety of medium perfusion rate conditions in a microfluidic perfusion cell culture platform. Five microcavities of $$800\,\upmu \hbox {m}~(w)\,\times \,800\,\upmu \hbox {m}~(l)\,\times \,400\,\upmu \hbox {m}~(h)$$ were adopted in order to minimize or isolate the shear effects on cell surfaces. Microchannels of $$800\,\upmu \hbox {m}~(w)\,\times \,3.5\,\hbox {mm}~(l)\,\times \,100\,\upmu \hbox {m}~(h)$$ serially connecting these microcavities created flow contractions and expansions repeatedly, resulting in two different diffusion and convection timescales through the platform. Average shear stresses on the bottom of microcavity were both numerically and analytically estimated, and medium flow was operated at rates where shear stress is below $$\sim$$ 2 mPa. Proliferation rates of CHO-K1 cells were investigated based both on population groups derived from the number of initially seeded cells and on the microcavity locations. Population groups showed minimal influences on proliferation rates, while proliferation rates increased clearly with medium perfusion rates. Strong effects of microcavity locations were observed on proliferation at $$\hbox {Pe}\,\ge \,45$$ . Such effects were analyzed by investigating the relationships of reaction, diffusion, and convection timescales associated with perfusion conditions. The ratio of diffusion timescale and convection timescale was suggested as a guideline to estimate the upper limit of perfusion rate in microfluidic perfusion cell culture platform.

Kinetic analysis is a tool used to glean additional information from positron emission tomography (PET) data by exploiting the dynamics of tissue metabolism. The standard irreversible and reversible two compartment models used in kinetic analysis were initially developed to analyse brain PET data. The application of kinetic analysis to PET of the liver presents the opportunity to move beyond the generic standard models and develop physiologically informed pharmacokinetic models that incorporate structural and functional features in particular to the liver. In this paper, we develop a new compartment model, called the tubes model, which is informed by the liver׳s sinusoidal architecture, high fractional blood volume, high perfusion rate, and large hepatocyte surface area facing the space of Disse. The tubes model distributes tracer between the blood and intracellular compartments in more physiologically faithful proportions than the standard model, producing parametric images with improved contrast between healthy and neoplastic tissue.

A 2D transmission line matrix model is used to study thermal transfer in living tissues exposed to laser energy. Damage size because of thermal coagulation in thermal treatment of benign prostate hyperplasia is determined quantitatively. Results show a quasilinear dependency of blood perfusion on temperature at the beginning of coagulation. Immediately thereafter, blood perfusion decreases considerably until it shuts down when the tissue under investigation has been coagulated. Increase in perfusion rate ω leads to high values of t100, which is the time required to reach a primary zone temperature of about 100i¾?C, and reflects the increased cooling created by perfusion. The transmission line matrix numerical model predicts the coagulation damage contours; that way, it has a clinical interest in therapy as an aid for clinicians because damage cannot be easily measured within patients. Results are validated through comparison with other researches. Copyright © 2014 John Wiley & Sons, Ltd.

This paper presents simulations of controlled hypothermia for the human head in view of improving the hypothermia process. We study the effect of head parameters, such as thickness of each region of the head (scalp, bone, gray matter, and white matter) heat generation rate, and blood perfusion rate, and the Peltier element cooling temperature on the behavior of the overall head cooling through induced controlled hypothermia. Two models are presented: one without heat generation rate and blood perfusion rate and the other—a more advanced model—with both heat generation rate and blood perfusion rate included. The results are described and discussed.

Sonication with fast scanning method can generate homogeneous lesions without complex planning. But when the target region is large, switching focus too fast will reduce the heat accumulation, the margin of which may not ablated. Furthermore, high blood perfusion rate will reduce this maximum volume that can be ablated. Therefore, fast scanning method may not be applied to large volume tumor. To expand the therapy scope, this study combines the fast scan method with multiple mode strategy. Through simulation and experiment, the feasibility of this new strategy is evaluated and analyzed.

Laser Doppler flowmetry (LDF) has been applied for the assessment of variation in blood microflows in patients with rheumatic diseases and healthy volunteers. Oscillations of peripheral blood microcirculation observed by LDF have been analyzed utilizing a wavelet transform. A higher amplitude of blood microflow oscillations has been observed in a high frequency band (over 0.1 Hz) in patients with rheumatic diseases. Oscillations in the high frequency band decreased in healthy volunteers in response to the cold pressor test, whereas lower frequency pulsations prevailed in patients with rheumatic diseases. A higher perfusion rate at normal conditions was observed in patients, and a weaker response to cold stimulation was observed in healthy volunteers. Analysis of blood microflow oscillations has a high potential for evaluation of mechanisms of blood flow regulation and diagnosis of vascular abnormalities associated with rheumatic diseases.

Ozdemir H, Memisoglu A, Alp-Unkar Z, Arcagok B, Bilgen H, Turan S, Ozek E. Persistent hyperglycemia in a neonate: Is it a complication of therapeutic hypothermia? Turk J Pediatr 2017; 59: 193-196. The aim of this report is to present a newborn with persistent hyperglycemia requiring insulin therapy as a possible complication of therapeutic hypothermia. A term appropriate for gestational age (AGA) female infant, was born by emergency cesarean section due to abruption of placenta and was resuscitated and intubated in the delivery room. Whole body cooling was initiated according to standard cooling criteria. The patient`s blood glucose increased up to 250 mg/dl on a glucose perfusion rate of 6 mg/kg/min after the second day of cooling. Insulin therapy was started due to persistent hyperglycemia and continued for 17 days. As it has been reported in adults after therapeutic cooling, persistent hyperglycemia attributed to hypothermia can also complicate therapeutic hypothermia in neonates.

Breast cancer is one of the leading cancer and the second leading cause of death in women worldwide. It can occur when cancer develops in breast tumor. The tumor tissue has generally higher metabolic and blood perfusion rate than normal tissue. It then causes the temperature rise in the in-vivo breast tissue. Previous researchers have studied the temperature profiles on the breast skin surface only with and without tumor. The aim of the present work is to study the temperature distribution profiles in the layers of breast tissue with and without tumor along the direction from aerola to the body core. Breast tumor can be occurred in any layers of breast tissue but most of the cancer cells are normally developed in glandular layer. So, the study is carried out based on the tumor in glandular layer. Pennes bio-heat equation is used to study the temperature variation in the layers of breast tissue. In the study, it is observed that the location and size of the tumor has significant effect on the breast tissue temperature.

Online and non-invasive quantification of critical tissue engineering (TE) construct quality attributes in TE bioreactors is indispensable for the cost-effective up-scaling and automation of cellular construct manufacturing. However, appropriate monitoring techniques for cellular constructs in bioreactors are still lacking. This study presents a generic and robust approach to determine cell number and metabolic activity of cell-based TE constructs in perfusion bioreactors based on single oxygen sensor data in dynamic perfusion conditions. A data-based mechanistic modeling technique was used that is able to correlate the number of cells within the scaffold (R(2) = 0.80) and the metabolic activity of the cells (R(2) = 0.82) to the dynamics of the oxygen response to step changes in the perfusion rate. This generic non-destructive measurement technique is effective for a large range of cells, from as low as 1.0 × 10(5) cells to potentially multiple millions of cells, and can open-up new possibilities for effective bioprocess monitoring.

In this paper, the temperature variation and consequent thermal stress and deformation during hypothermic perfusion are numerically investigated. Hypothermic perfusion is the first step of preservation techniques that washes out of the vascular system and provides the supply of substrates and cools the kidney to the preservation temperature. A three-dimensional (3D) finite element analysis using the anatomical CAD model of kidney is developed to accurately simulate the hypothermic perfusion process. Based on the temperature field, the time evolution of thermal stress and deformation distribution are obtained. In addition, we analyze the effect on the thermal stress and deformation which cannot be easily acquired through clinical experiments. The results indicate that the thermal effects of large blood vessels could remarkably affect the temperature, thermal stress and deformation distributions. Increasing the perfusion rate could enlarge the thermal deformation, which causes the injury to the kidney. These results provide a guideline to the basic and applied research for the thermal effect on the hypothermic perfusion of kidney.

Continuous processes such as perfusion processes can offer advantages compared to fed‐batch or batch processes in bio‐processing: improved product quality (e.g. for labile products), increased product yield, and cost savings. In this work, a semi‐perfusion process was established in shake flasks and transferred to an automated small‐scale bioreactor by daily media exchange via centrifugation based on an existing fed‐batch process platform. At first the development of a suitable medium and feed composition, the glucose concentration required by the cells and the cell‐specific perfusion rate were investigated in shake flasks as the conventional scale‐down system. This lead to an optimized process with a threefold higher titer of 10 g/L monoclonal antibody compared to the standard fed‐batch. To proof the suitability and benefit as a small‐scale model, the established semi‐perfusion process was transferred to an automated small‐scale bioreactor with improved pH and dissolved oxygen control. The average specific productivity improved from 24.16 pg/(c*d) in the fed‐batch process and 36.04 pg/c*d in the semi‐perfusion shake flask to 38.88 pg/(c*d) in the semi‐perfusion process performed in the controlled small‐scale bioreactor, thus illustrating the benefits resulting from the applied semi‐perfusion approach, especially in combination with controlled DO and pH settings. © 2019 The Authors. Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 35: e2757, 2019.

Presence of a tumor and its characteristics like location, size and properties are estimated. Estimation is based on the measurement of the skin surface temperature of the breast. Consideration is given to a 2-D breast tissue infected with a tumor. Heat transfer in the breast tissue modeled using the Pennes bioheat equation is solved by the finite volume method. Skin surface temperature profile of the breast is characteristic of the tumor location, its size and grade. In the inverse analysis, the objective function is minimized using the genetic algorithm. Exact estimation is obtained if one parameter is estimated at a time. However, the accuracies are acceptable even when blood perfusion rate, location and size are estimated simultaneously.

Structural blood networks and blood perfusion rate of a tumor impact the manner in which cryosurgery is carried. In locations where complex vascular systems exist, the freezing temperature of the cryoprobes must account for these additional heat sources while maximizing the eradication of cancer cells. In this study, a computational cryo-freezing model that incorporates a simplified mathematical description of the vascular morphology has been constructed. Complex vascular network with varied blood flows were simplified and modeled as tree-like branched fractal network. The present work evolved a simplified and time-saving methodology to accurately simulate complex blood vessel network in order to reduce simulation tediousness and computational cost. A thermal freezing algorithm has been employed to generate transient temperature profiles, to visualize isotherms in the anatomical region of interest and to provide essential information the ice-front propagation. Extensive experimental validation of the proposed model has been performed with good agreement of up to 4.3%. Effects of combining cryosurgery with advanced nanotechnology to better regulate ice-ball development within a biological tissue were quantitatively investigated. Depending on the thermal properties of different nanoparticles, they could either enhance heat conduction or retard freezing to minimize unintended cryoinjury to the neighboring tissue. Hence, key results have confirmed that while certain nanoparticles act as therapeutic freezing agents that promote cryoablation, others are capable of protecting surrounding healthy tissue.

Extreme environmental and physiological conditions present challenges for thermal processes in body tissues including multi-layered human eye. A mathematical model has been formulated in this direction to study the thermal behavior of the human eye in relation with the change in blood perfusion, porosity, evaporation and environmental temperatures. In this study, a comprehensive thermal analysis has been performed on the multi-layered eye using Pennes' bio-heat equation with appropriate boundary and interface conditions. The variational finite element method and MATLAB software were used for the solution purpose and simulation of the results. The thermoregulatory effect due to blood perfusion rate, porosity, ambient temperature and evaporation at various regions of human eye was illustrated mathematically and graphically. The main applications of this model are associated with the medical sciences while performing laser therapy and other thermoregulatory investigation on human eye.

The multi-dimensional impact of physical exercise upon psychology and behavioural science is linked to the manifest healthbeneficial expressions of physical exercise over individuals’ life-cycles, whether normal or in ill-health, may be encapsulated within several domains of welfare: (i) exercise and academic and other cognitive performances, (ii) exercise and the developmental trajectory, (iii) exercise for the alleviation of affective disorders, and (iv) the epigenetic manifestations of physical exercise. Surprisingly, the effects of exercise may be determined relatively quickly: just eight weeks of pre-season training on body composition, physical fitness, anaerobic capacity, and isokinetic strength in collegiate taekwondo athletes in endurance gave improvements on all these parameters, as assessed by relative peak power and anaerobic capacity and angular velocity [1]. Psychological well-being, cognitive, emotional, motor, behavioral, clinical, recuperative, epigenetic and health domains all make considerable impact upon individuals’ propensity for and compliance with regular exercise and physical activity and vice versa throughout the lifespan development [2-16]. Accordingly, physical exercise is viewed as a “scaffolding” construct that buttresses against illness and damage incurred under conditions, such as traumatic brain injury, clinical depression, developmental disorders or neurodegenerative diseases and aging, by shaping conditions for construction, damage control and reconstruction. It furnishes ongoing processes that are maintained across the lifespan through the applications and development of complementary, alternative biomarkers and neural networks for the attainment of selected functions and performances [17,18]. For example, [19], using data from the ageing population of the “Betula” study (Umea, Sweden) have shown that (i) higher levels of physical activity score were related to greater connectivity in the posterior default-mode network, (ii) higher levels of physical activity score were related to larger gray matter volume of the posterior cingulate cortex, and (iii) higher levels of physical activity score were related to higher perfusion rate within the posterior cingulate cortex.

Laser speckle imaging was used to monitor blood flow dynamics during and after vascular-targeted photodynamic therapy (V-PDT). The results show that blood flow and blood perfusion rate was decreased after V-PDT, while the blood flow in veins could be partially increased after treatment. This study suggest that the LSI system hold the potential for quantitative assessment of vascular damage for V-PDT.

A fed-batch process for the production of biosimilar monoclonal antibody was developed. Since the brand product is produced by perfusion process, the impact of process change from perfusion to fed-batch on product quality and cell performance was evaluated. Perfusion culture was performed at 0.47–1.00 (v/v/d) perfusion rate by spin-filter method with 15–17 μm mesh. Culture parameters such as pH (6.8–7.2), dissolved oxygen (40–70% air saturation), temperature (37 °C) and agitation speed (250 rpm) were applied in both culture modes. In terms of cell performance, volumetric productivity increased 3.7 times while process performance increased 7.5 times in fed-batch culture due to 10 times higher scalability. Considering the glycosylation pattern and charge variants, no significant changes in product quality were observed upon process change, although intact IgG level slightly decreased in fed-batch mode. The change of production media showed more effect on glycosylation patterns than the operation in different culture modes. Furthermore, there were no differences in biological activity, including TNFα, FcγRIIIa, and C1q-binding affinity. Through a scale-up study from 3 L to 12,500 L, it was confirmed that cell performance and product quality could be maintained. In conclusion, product quality of the fed-batch process was comparable to that of the reference product.

Aims Recurrences of ventricular fibrillation (VF) during cardiopulmonary resuscitation (CPR) are associated with a reduced chance of survival. The effect of VF during CPR on the myocardium is unknown. We tested the hypothesis that VF during simulated CPR reduces the restoration of the myocardial energy state and contractile function. Methods and results Twelve porcine hearts were isolated and perfused with the pig's own blood. First, cardiac oxygen consumption was measured by blood gas analysis. Secondly, we simulated sudden cardiac arrest by VF (7 min VF, zero flow) followed by simulated CPR (7 min, 0.3 mL/g/min perfusion rate) in the absence and presence of VF [six hearts were maintained in VF (VF-group), six were defibrillated (defib-group)]. The VF increased the cardiac oxygen consumption by 71% (0.87 +/- 0.12 vs. 1.49 +/- 0.14 mu mol O-2/g/min; mean +/- SEM, P

Cerebral microdialysis is a chemical detection method capable of identifying and simultaneously sampling a wide range of substances in the micromilieu of the monitoring probe. The interstitial space of biological tissues and fluids is sampled through a thin fenestrated dialysis catheter inserted into the brain. The technique has been reported in patients with Parkinson's disease. However, the procedure is not widely used by neurosurgeons, possibly owing to unclear indications and poor effective benefits, mostly secondary to significant pitfalls. In spite of the feasibility of microdialysis in humans, many factors can affect the quality of the process. Possible pitfalls include improperly designed probe, probe insertion effects, ineffective perfusion rate, issues to optimize stabilization period, and insufficient volume sample. This article reviews those key technical features necessary for performing microdialysis in humans during deep brain stimulation for Parkinson's Disease.

BACKGROUND: The progressive deterioration of red blood cell (RBC) rheologic properties during refrigerated storage may reduce the clinical efficacy of transfusion of older units. STUDY DESIGN AND METHODS: This article describes the development of a microfluidic device designed to test the rheologic properties of stored RBCs by measuring their ability to perfuse an artificial microvascular network (AMVN) comprised of capillary-size microchannels arranged in a pattern inspired by the real microvasculature. In the AMVN device, the properties of RBCs are evaluated by passing a 40% hematocrit suspension of RBCs through the network and measuring the overall perfusion rate. RESULTS: The sensitivity of the AMVN device to the storage-induced change in rheologic properties of RBCs was tested using five prestorage leukoreduced RBC units stored in AS-1 for 41 days. The AMVN perfusion rate for stored RBCs was 26 ± 4% (19%-30%) lower than for fresh RBCs. Washing these stored RBCs in saline improved their performance by 41 ± 6% (the AMVN perfusion rate for washed stored RBCs was still 15 ± 2% lower than for fresh RBCs). CONCLUSIONS: The measurements performed using the AMVN device confirm a significant decline in the rheologic properties of RBCs in units nearing expiration and demonstrate the sensitivity of the device to these storage-induced changes. The AMVN device may be useful for testing the effect of new storage conditions, additive solutions, and rejuvenation strategies on the rheologic properties of stored RBCs in vitro.

We report on a pumpless cell culture chip in which a constant medium perfusion rate is maintained by balanced droplet dispensing. Previous chips had a decreasing perfusion rate due to the decreasing hydraulic-head difference between the inlet and drain. However, the present chip maintains a constant medium perfusion rate due to the constant between the inlet and drain maintained by balanced droplet dispensing. The perfusion rate Q was measured to be 0.1-/min with a maximum deviation and error of 9.96% and 6.92%, respectively. In the perfusion culture (Q = 0.1-/min), the maximum growth-rate of H358 cells was measured to be per day, which is 1.9 times higher than that of a static culture. The perfusion culture also resulted in higher cell viability than a static culture. The present chip offers a favorable environment with a high growth-rate and viability and thus has potential for use in the integrated cell culture system.

The purpose of this study was to examine with the help of thermal imaging the heat effects caused by the non-ionizing radiation of mobile phone and the protective properties of the MRETNylon polymer device in neutralizing or eliminating the thermal effects in the body. The current study shows that the exposure of human subjects to the microwave radiation of cellular phone results in the measured increase of the body temperature. It also showed that the installation of the MRET-Nylon protective device on a RF phone significantly reduced or negated the thermal effects caused by RF phone and even leaded to the cooling pattern comparing to the standard cool-down state. Those result are well correlated with the accepted physical model which explains the relationship between the elevation of the body temperature with increased specific absorption rate of electromagnetic radiation (SAR) and increased blood perfusion rate (Green’s function) usually following the human body exposure to EMR.

We investigated the disposition of ARTCEREB® irrigation and perfusion solution (Artcereb) during intrathecal perfusion in a lateral ventricle-cisternal perfusion model in conscious rats. In this perfusion model, the perfusion rate was set at 0.35 ml/kg/h, taking into consideration the clinical perfusion rate (500 ml/60 kg/d). The influence of Artcereb on electrolytes in cerebrospinal fluid (CSF) and blood were then investigated. After 24 h of ventriculocisternal perfusion with Artcereb using the push-pull method, output of K(+), Na(+) and Cl(-) to the cistern magna was very similar to input of these electrolytes in Artcereb infused intraventricularly. Recovery rates of K(+), Na(+) and Cl(-) after perfusion were 102%, 105% and 100% when calculated using the recovered perfusion solution. In addition, concentrations of K(+), Na(+) and Cl(-) in blood remained almost constant at near baseline levels throughout perfusion. Thus, intrathecally perfused Artcereb did not affect electrolyte balance in the CSF and blood. To confirm the dynamics of Artcereb distribution, a whole body autoradiography study was performed at 1 and 6 h after perfusion with ¹⁴C-inulin-added Artcereb. Radioactivity was detected in the entire CSF space of the brain, and the cribriform plate in the nasal cavity, and the cerebrospinal cavity. Radioactivity was observed in the bladder, thus suggesting that some ¹⁴C-inulin was transferred to the bloodstream via a physiological route, and was excreted renally.

In magnetic nanoparticle hyperthermia for cancer treatment, controlling the heat distribution and temperature elevations is an immense challenge in clinical applications. It is expected for treatment quality to understand the heat transport occurring in biological tissue. The non-Fourier thermal behavior in biological tissue has been experimentally observed. This work uses the thermal wave model to predict the temperature excess occurring in a two-layer concentric spherical tissue with the heat source of Gaussian distribution. The solutions to the hyperbolic bio-heat equation with the space-dependent source term in the spherical coordinate system are presented. The influences of relaxation time, blood perfusion rate, and heating strength on the thermal response in tumor and normal tissue are discussed.

The development of microfluidic hydrogels is an attractive method to generate continuous perfusion, induce vascularization, increase solute delivery, and ultimately improve cell viability. However, the transport processes in many in vitro studies still have not been realized completely. To address this problem, we have developed a microchanneled hydrogel with different collagen type I concentrations of 1, 2, and 3 wt% and assessed its physical properties and obtained diffusion coefficient of nutrient within the hydrogel. It is well known that microchannel geometry has critical role in maintaining stable perfusion rate. Therefore, in this study, a computational modeling was applied to simulate the 3D microfluidic hydrogel and study the effect of geometric parameters such as microchannel diameters and their distance on the nutrient diffusion. The simulation results showed that the sample with 3 channels with a diameter of 300 μm has adequate diffusion rates and efficiency (56%). Moreover, this system provides easy control and continuous perfusion rate during 5 days of cell culturing. The simulation results were compared with experimental data, and a good correlation was observed for nutrient profiles and cell viability across the hydrogel.

A hybridoma producing monoclonal antibody (MAb) specific for enrofloxacin was cultivated in a 2-L stirred-tank bioreactor in various modes and the performances of each mode were compared. In batch mode, a maximum viable cell and MAb concentration of 9.21 × 10 5 cells mL −1 and 67.3 mg L −1 , respectively, were obtained. When the hybridoma was cultivated in a fed-batch culture with the addition of specific nutrients, no improvement in either the viable cell number or MAb concentration was observed. On the other hand, an increase in the production of toxic metabolites, i.e. ammonia and lactate, was observed with growth inhibition of the hybridoma cells occurring at ammonia and lactate concentrations of 2.0 mM and 2.0 g L −1 , respectively. However, the best performance of hybridoma cultivation was achieved in a perfusion culture mode using a spin filter, which was installed in the stirred-tank reactor as a cell retention device with a perfusion rate of 0.80 vvd. Under these conditions a steady viable cell concentration of 1.57 × 10 6 cells mL −1 was obtained within five days with an overall productivity and yield of 73.7 mg L −1 d −1 and 61.4 mg d −1 , respectively, which was a significant increase over that attained with the batch process.

Intermittent energy application seems to have positive effects in achieving necrotic zones. We analyzed different pulse periods (PPs) to optimize this method. A radiofrequency alternating current was delivered via a triple-needle applicator (3 cm distance of each needle) introduced into freshly procured bovine liver. The open applicator system was constantly perfused with physiological NaCl solution (3×80 ml/h, power output was constant 90 W). Radiofrequency current was fed to the individual needle in turn of varying PPs (1, 2, 5, and 7 s) over 15 min. Each experimental run comprised a total of 30 applications and temperature was recorded over time. The largest necrotic diameters were found at PP 1 s (relevant: shortest axial diameter/D in the center of the lesion: 9.27 cm, SD±0.97 cm) (PP 2 s D=8.65 cm, SD±0.95 cm, p=0.021; PP 5 s D=8.35 cm, SD±0.95 cm, p=0.001; PP 7 s D=8.18 cm, SD±0.79 cm, p=0.0001). Neither doubling the perfusion rate nor raising the concentration of the perfusion liquid led at PP 1 s to increased necrotic diameters (p=0.82). Our study shows that reducing the PP to 1 s of an open perfused intermittent radiofrequency ablation system produces significantly larger coagulation volumes in explanted liver tissue reaching necrotic diameters over 9 cm. Neither doubling perfusion rates nor higher concentrated perfusion liquid increase necrotic diameters.

The living tissue self-regulation is considered as an example of the general problem of adapting and self-sustaining of active fractal systems of biological, ecological, and social nature. A distinctive feature of such systems is the absence of a unified governing center. Their self-regulation is based on cooperative distributed interaction between all elements. A mathematical description of the response of the vascular network in individual organs to local effects is developed. A model for self-processing of information about the state of cellular tissue and cooperative interaction of blood vessels under distributed control of blood circulation in the vascular network is formulated. The law of conservation of, in particular, blood and transported chemical compounds at the nodes of the vascular network plays a key role in the description of these processes. The arterial and venous beds are assumed to be of the tree form. The vascular network behavior is described in terms of the individual response of blood vessels to the concentration of activator in blood flowing through them. The equations obtained are solved numerically. First, it is shown in the first approximation that the blood perfusion rate is a local function of the activator concentration in the cellular tissue, which is due to the hierarchical structure of the vascular network. Second, a fundamental difference is found between the threshold of individual vessel response to the concentration of activator in blood and the threshold response of the vascular network as a whole to the presence of activator in the cellular tissue. Third, it is shown that the blood perfusion rate can be essentially nonuniform in space. Fourth, the nonlocal dependence of perfusion rate on activator concentration is found to change its form with increasing activator concentration.

Recently, hyperthermia has been investigated as an alternate therapy for the treatment of tumors. This paper explored the feasibility of preferential hyperthermia as a method of treating deep seated tumors. The overall goal of this research was to determine theoretically if preferential heating could be used to attain the desired thermal dose (DTD) for a two cm diameter tumor. The simulations in this work show that, when using a single rod insert, the model cannot provide enough energy for an entire 2 cm diameter tumor to receive the DTD. However, when using an enhanced design model with multiple (4) rods inserts, the DTD could be attained in a tumor up to 3.5 cm in diameter. This study involved using the model a spherical 2 cm tumor, assuming the tumor is located in deep tissue with a constant perfusion rate and no major blood vessels nearby. This tumor was placed in the center of a cube of healthy tissue. To achieve the preferential heating of the tumor, a rod insert was placed in the center of the tumor and microwave energy was applied to the insert (in the form of volumetric heating). The thermal modeling of this system was based on the Pennes Bioheat equation with a maximum temperature limitation of 80 ◦ C. Additional enhanced design models were also examined. These models include 2 cm and 4 cm tumors with four rod inserts symmetrically placed about the tumor and a 4 cm tumor model using a single rod insert with antennae attached to insert to increase energy distribution to the tumor. The simulations show that only the enhanced design cases with four rods inserts can achieve the DTD for an entire 2 cm tumor. The main purpose of this research was to determine if a minimally invasive treatment system using one or more rod inserts could be used to preferentially heat (and attain the DTD) a 2 cm diameter (or larger) tumor. Achieving the DTD for a 2 cm or larger tumor was important because currently the maximum diameter tumor that can be treated via hyperthermia is approximately

The heat transfer mechanism of tongue was investigated on the basis of experimental and theoretical research. Firstly, the relationship between tongue temperature and blood perfusion was obtained from animal experiment that mainly carried out on porcine tongue, subordinate on human tongue. Secondly, a one-dimensional variable coefficients second-order inhomogeneous heat transfer equation is developed by simplifying tongue as fin cube and the analytical solution is got. The results show that the change regulations of temperature by blood perfusion rate are the same in human and porcine tongue, and also, there is a good agreement between calculation and experimental results. When checking the model with corresponding properties of human tongue, the result is also satisfied. In conclusion, predicting temperature distribution of tongue is feasible with the fin cube model.

Present surgical techniques are rarely relying on intestinal intramural vascular anastomoses; however, this could open new limits in reconstructive surgery. Our aim was to study the efficacy of the antimesenteric and the longitudinal intramural vascular anastomoses in a porcine model.Five minipigs were used. Antimesenteric anastomoses: jejunal loops were detubularized by cutting along the antimesenteric line (Control), in the middle between the mesenteric and antimesenteric border (Group 1) and close to the mesenteric line (Group 2). Mucosal microcirculation (red blood cell velocity, perfusion rate) was recorded with orthogonal polarization spectral imaging (Cytoscan A/R) at the long edge of the detubularized bowel. Longitudinal anastomoses: records were made on a continuous jejunal loop following antimesenteric incision, detubularization, and subsequent ligation of 2, 4, and 6 neighboring vasa recta in the middle of the loop. The same study was repeated on the free end of completely divided jejunal segments with ligation of 2, 4, or 6 vasa recta.Antimesenteric anastomoses: There was no statistically significant difference in red blood cell velocity and perfusion rate between Control and Groups 1 and 2. Longitudinal anastomoses: The red blood cell velocity dropped significantly, while the perfusion rate did not change significantly after ligation of 4 vasa recta in the continuous loop. In the loop with a free end, however, both parameters decreased significantly after ligation of four vessels.It is safe to rely on antimesenteric intramural anastomoses but strong limitation of longitudinal intramural vascular anastomoses should be considered in intestinal reconstructions.

Purpose: This study investigates the influence of blood perfusion variability within a tumour and the surrounding healthy tissue during nanoparticle-assisted thermal therapy. It seeks to define ideal therapeutic parameters for a wide range of perfusion rates to attain the desired thermal damage. Material and methods: Pennes’ bioheat model and the Arrhenius model are used to evaluate the thermal damage for a two-dimensional tumour surrounded by healthy tissue. A wide range of tumour perfusion rates were modelled, ranging from moderate to high perfusion in both a homogenously and a heterogeneously perfused tumour. Results: For low perfusion rates, a temporal variation in blood perfusion does not critically influence the thermal damage. For moderately and highly perfused tumours, temporal variation in blood perfusion extends the thermal damage zone by 25–52% compared to a constant perfusion rate. For the tumour size and perfusion conditions under consideration, the ideal therapeutic parameters were found to be irradiation intensity of 1 W/cm2, and irradiation duration of 105–150 s, for a nanoparticle volume fraction of 0.001%. Conclusions: It is concluded for low perfusion rates that due to shorter therapeutic duration, nanoparticle-assisted thermal therapy is relatively insensitive to changes in the perfusion rate during the therapy. For moderately and highly perfused tumours, a constant perfusion under-predicts the real thermal damage zone. This study concludes that for moderately and highly perfused tumours the spatial as well as temporal blood perfusion dynamics should be carefully accounted for to get a realistic estimate of thermal damage zone.

BACKGROUND The aim of this research was to study the effectiveness of perfusion of intact ovine ovaries with different rates of perfusion and time-period elapsed between extraction of these ovaries and the beginning of perfusion. METHODS Ovaries were perfused through the arteria ovarica (ovarian arteries) with culture medium supplemented with 5% bovine calf serum, 6% dimethyl sulfoxide, 6% ethylene glycol, 0.15M sucrose, Indian ink, and 100 IU/mL heparin at room temperature (22 degrees C). In the first cycle of experiments, ovaries (n = 96) were perfused for 60 minutes just after extraction of ovaries at the following rates of perfusion (mL/hour): 150, 100, 75, 50, 25, 12.5, and 6.3. In the second cycle of experiments, ovaries (n = 26) were perfused at a rate of 25 mL/hour for 60 minutes after extraction of ovaries and their storage at room temperature for 2, 3, 4, and 5 hours, for groups 1, 2, 3, and, 4, respectively. Successful perfusion of blood vessels was detected visible by a blue coloration of the ovarian tissues. RESULTS The first cycle of experiments showed that the optimal perfusion rates were 50 mL/hour and 25 mL/hour. In the second cycle of experiments, good perfusion of ovaries was established at a perfusion rate of 25 mL/hour for the ovaries of groups when 2 and 3 hours had elapsed after extraction. CONCLUSIONS Effective perfusion of ovine intact ovaries with vascular pedicle was established using freezing medium at room temperature at the rate of perfusion of 25 mL/hour or 50 mL/hour. The ovaries must be perfused not later than 3 hours after the death of animals.

Acoustic cell filters operate at high separation efficiencies with minimal fouling and have provided a practical alternative for up to 200 L/d perfusion cultures. However, the operation of cell retention systems depends on several settings that should be adjusted depending on the cell concentration and perfusion rate. The impact of operating variables on the separation efficiency performance of a 10-L acoustic separator was characterized using a factorial design of experiments. For the recirculation mode of separator operation, bioreactor cell concentration, perfusion rate, power input, stop time and recirculation ratio were studied using a fractional factorial 2(5-1) design, augmented with axial and center point runs. One complete replicate of the experiment was carried out, consisting of 32 more runs, at 8 runs per day. Separation efficiency was the primary response and it was fitted by a second-order model using restricted maximum likelihood estimation. By backward elimination, the model equation for both experiments was reduced to 14 significant terms. The response surface model for the separation efficiency was tested using additional independent data to check the accuracy of its predictions, to explore robust operation ranges and to optimize separator performance. A recirculation ratio of 1.5 and a stop time of 2 s improved the separator performance over a wide range of separator operation. At power input of 5 W the broad range of robust high SE performance (95% or higher) was raised to over 8 L/d. The reproducible model testing results over a total period of 3 months illustrate both the stable separator performance and the applicability of the model developed to long-term perfusion cultures.