bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Dietary Restriction on Mitochondrial Dysfunction in Aginga
Authors: FEUERS RITCHIE J.
Published: February 2006

ABSTRACT: Age‐associated alterations in the mitochondrial electron transport system (ETS) may lead to free radical generation and contribute to aging. The complexes of the ETS were screened spectrophotometrically in gastrocnemius of young (10 month) as well as older (20 and 26 month) B6C3F1 female mice fed an ad libitum (AL) diet or a restricted (DR) in total calories diet (40% less food than AL mice). The activities of complexes I, III, and IV decreased significantly by 62%, 54%, and 74%, respectively, in old AL mice (AL20) compared to young AL mice (AL10). Complexes I, III, and IV from DR10 mice had activities that were significantly lower than those seen in AL10 mice (suggesting a lower total respiratory rate or improved efficiency). By contrast, complex II activity did not decrease with age (actually increased, but not significantly) in AL20 mice. Complex II was decreased across age in DR mice. Km for ubiquinol‐2 of complex III was significantly increased in AL10 animals (0.33 mM vs. 0.26 mM in DR10 mice) and was further increased with aging (0.44 mM in AL20 vs. 0.17 mM in DR20 mice). This suggests obstruction of binding, inhibition of electron flow in aging, which could yield premature product release as a free radical. Total complex IV by Vmax was highest in AL10 mice, but the proportion of complex as high‐affinity sites was lower (69%) than in either DR10 (80%) or DR20 (80%). The percentage of high‐affinity sites decreased to only 45% in AL20 mice, and Vmax was reduced by 75 percent. In AL26 mice high‐affinity sites decreased to 33 percent. At physiologic concentration of reduced cytochrome c, significant dysfunction of complex IV in AL20 or AL26 mice would be expected with obstruction of overall electron transport. The age‐associated loss of activity and function of complexes I, III, and IV may contribute to increased free radical production. Lack of sufficient DNA repair in mitochondria and juxtaposition to the ETS adds to susceptibility and accumulation of mtDNA and other mitochondrial macromolecular damage. DR seems to retard this deterioration of mitochondrial respiratory function by preserving enzymatic activities and function.
Mitochondrial Decay in Aging: Reversal through Supplementation of Acetyl‐l‐Carnitine and N‐tert‐Butyl‐α‐phenyl‐nitronea
Authors: HAGEN TORY M. , WEHR CAROL M. , AMES BRUCE N.
Published: February 2006

ABSTRACT: We show that mitochondrial function in the majority of hepatocytes isolated from old rats (24 mo) is significantly impaired. Mitochondrial membrane potential, cardiolipin levels, respiratory control ratio, and overall cellular O2 consumption decline, and the level of oxidants increases. To examine whether dietary supplementation of micronutrients that may have become essential with age could reverse the decline in mitochondrial function, we supplemented the diet of old rats with 1% (w/v) acetyl‐l‐carnitine (ALCAR) in drinking water. ALCAR supplementation (1 month) resulted in significant increases in cellular respiration, mitochondrial membrane potential, and cardiolipin values. However, supplementation also increased the rate of oxidant production, indicating that the efficiency of mitochondrial electron transport had not improved. To counteract the potential increase in oxidative stress, animals were administered N‐tert‐butyl‐a‐phenyl‐nitrone (30 mg/kg) (PBN) with or without ALCAR. Results showed that PBN significantly lowered oxidant production as measured by 2,7′‐dichlorofluorescin diacetate (DCFH), even when ALCAR was coadministered to the animals. Thus, dietary supplementation with ALCAR, particularly in combination with PBN, improves mitochondrial function without a significant increase in oxidative stress.
Mitochondrial Free Radical Production and Aging in Mammals and Birdsa
Authors: BARJA GUSTAVO
Published: February 2006

ABSTRACT: The mitochondrial rate of oxygen radical (ROS) production is negatively correlated with maximum life span potential (MLSP) in mammals following the rate of living theory. In order to know if this relationship is more than circumstantial, homeothermic vertebrates with MLSP different from that predicted by the body size and metabolic rate of the majority of mammals (like birds and primates) must be studied. Birds are unique because they combine a high rate of basal oxygen consumption with a high MLSP. Heart, brain, and lung mitochondrial ROS production and free radical leak (percent of total electron flow directed to ROS production) are lower in three species of birds of different orders than in mammals of similar body size and metabolic rate. This suggests that the capacity to show a low rate of ROS production is a general characteristic of birds. Using substrates and inhibitors specific for different segments of the respiratory chain, the main ROS generator site (responsible for those bird‐mammalian differences) in state 4 has been localized at complexes I and III in heart mitochondria and only at complex I in nonsynaptic brain mitochondria. In state 3, complex I is the only generator in both tissues. The results also suggest that the iron‐sulphur centers are the ROS generators of complex I. A general mechanism that allows pigeon mitochondria to show a low rate of ROS production can be the capacity to maintain a low degree of reduction of the ROS generator site. In heart mitochondria, this is supplemented with a low rate of oxygen consumption physiologically compensated with a comparatively higher heart size. A low rate of free radical production near DNA, together with a high rate of DNA repair, can be responsible for the slow rate of accumulation of DNA damage and thus the slow aging rate of longevous animals.
Oxidative Damage in the Senescence‐accelerated Mouse
Authors: MORI AKITANE , UTSUMI KOZO , LIU JIANKANG , HOSOKAWA MASANORI
Published: February 2006

ABSTRACT: The senescence‐accelerated mouse (SAM) exhibited a shortened life span (about 18 months) and early manifestation of various signs of senescence, including changes in physical activity, skin, and spinal curvature. The mechanism of senescence acceleration in SAM is thought to be related to free radical damage. Oxidative phosphorylation was estimated in liver mitochondria from SAMPS and the senescence‐resistant subtrain, SAMR1. The respiratory control ratio decreased during aging, and the ATP/O, an index of ATP synthesis, was depressed at 18 months of age in SAMPS. DNP‐dependent uncoupled respiration in liver mitochondria was markedly decreased, and active uptake of calcium was markedly dysfunctional with aging. These findings suggest that the functional disorders in mitochondria may be closely related to the shorter life span of SAMPS. White‐footed (WF) mice can live at least to 5.5 years, when some animals are still capable of reproducing and their external body condition remains healthy. The mitochondrial functions were examined in the same way as in the SAM experiments. However, no particular finding responsible for their longevity was observed in WF mice at 3 and 12 months old. More comprehensive examinations on more aged WF mice are needed for explanation of their greater longevity.
Membrane and Receptor Modifications of Oxidative Stress Vulnerability in Aging: Nutritional Considerations
Authors: JOSEPH J. A. , DENISOVA N. , FISHER D. , SHUKITT‐HALE B. , BICKFORD P. , PRIOR R. , CAO G.
Published: February 2006

ABSTRACT:Evidence suggests that oxidative stress (OS) may contribute to the pathogenesis of age‐related decrements in neuronal function and that OS vulnerability increases as a function of age. In addition to decreased endogenous protection, increases in OS vulnerability may result from changes in membrane lipids and distribution of receptor subtype. Using a PC‐12 cell model system, we have shown that H2O2or dopamine (DA) exposure induced deficits in the cell's ability to clear (extrude/sequester, E/S) Ca2+that are similar to those seen in aging. When plasma membrane concentrations of sphingomyelin (SPM) were used, the SPM metabolite, sphingosine‐1‐phosphate was increased to the same levels as those seen in aging, and enhancement of OS‐induced decreases in calcium E/S following KCL depolarization was observed. Differential decreases in CA2+E/S were also seen following DA‐induced OS in COS‐7 cells transfected with one of five muscarinic receptor subtypes. Cells transfected with either M1, M2, or M4 receptors showed significantly greater vulnerability to OS (as expressed by greater decrements in calcium E/S and cell death) than those transfected with M3 or M5 receptors. The vitamin E analogue, Trolox, and the nitrone‐trapping agent, PBN, were not effective in altering E/S decrements but were effective in preventing cell death 24 h after OS exposure. These findings suggest that putative regional (e.g., striatum and hippocampus) increases in OS vulnerability and loss of neuronal function in aging may be dependent upon membrane SPM concentration and receptor subtype. In related studies, attempts were made to determine whether increased OS protection via nutritional increases in antioxidant levels in rats [using diets supplemented with vitamin E (500 IU/kg), strawberry extracts (9.4 g/kg dried aqueous extract, DAE), spinach (6.7 g/kg DAE), or blueberry extracts (10 g/kg DEA for six weeks)] would protect against exposure to 100% O2 (a model of accelerated neuronal aging). Results indicated that these diets were effective in preventing OS‐induced decrements in several parameters (e.g., nerve growth factor decreases), suggesting that although there may be increases in OS vulnerability in aging, phytochemicals present in antioxidant‐rich foods may be beneficial in reducing or retarding the functional central nervous system deficits seen in aging or oxidative insult.
Redox Regulation of the Caspases during Apoptosisa
Authors: HAMPTON MARK B. , FADEEL BENGT , ORRENIUS STEN
Published: February 2006

ABSTRACT: Apoptosis is now widely recognized as being a distinct process of importance both in normal physiology and pathology. In the current paradigm for apoptotic cell death, the activity of a family of proteases, caspases, related to interleukin‐1β‐converting enzyme (ICE) orchestrates the multiple downstream events, such as cell shrinkage, membrane blebbing, glutathione (GSH) efflux, and chromatin degradation that constitute apoptosis. Recent studies suggest that mitochondria could be the principle sensor and that the release of mitochondrial factors, such as cytochrome c, is the critical event governing the fate of the cell. One of the most reproducible inducers of apoptosis is mild oxidative stress, although it is unclear how an oxidative stimulus can activate the caspase cascade. Oxidative modification of proteins and lipids has also been observed in cells undergoing apoptosis in response to nonoxidative stimuli, suggesting that intracellular oxidation may be a general feature of the effector phase of apoptosis. The caspases themselves are cysteine‐dependent enzymes and, as such, appear to be redox sensitive. Indeed, our recent work on hydrogen peroxide‐mediated apoptosis suggests that prolonged or excessive oxidative stress can actually prevent caspase activation. A physiological example of this is the NADPH oxidase‐derived oxidants generated by stimulated neutrophils that prevent caspase activation in these cells. Pursuant to these findings, stimulated neutrophils appear to use a specialized caspase‐independent pathway to initiate phosphatidylserine (PS) exposure and subsequent phagocytic clearance. The possible implications of these dual roles for reactive oxygen species in apoptosis, that is, induction and inhibition of caspases, are discussed in the present review.
Combined Exercise and Dietary Intervention to Optimize Body Composition in Aging
Authors: SINGH MARIA A. FIATARONE
Published: February 2006

ABSTRACT: Concomitant losses of skeletal muscle and bone mass along with gradual accretion of adipose tissue typify usual human aging. Recent investigations have attempted to modify these processes with various combinations of dietary and exercise intervention in older adults. Complete nutritional supplements given with weight‐lifting exercise have been shown to augment muscle and fat gains in healthy older men, but have merely suppressed habitual dietary intake when administered to frail sedentary elders, and have not altered body composition responses to strength training in this population. Protein supplementation at twice the RDA does not improve skeletal muscle function or increase muscle mass in healthy elderly weight lifters compared to those on a normal diet. Calcium supplementation during one year of aerobic training has an independent beneficial effect on cortical bone density at the femoral neck in postmenopausal women, whereas the exercise is associated with trabecular bone increases in the lumbar vertebrae. Hypocaloric dieting, with or without aerobic exercise, results in losses of weight, fat and lean mass in obese elderly men and women. By contrast, resistance training during hypocaloric dieting augments lean mass while further reducing fat mass. Low protein, isoenergetic diets result in muscle atrophy in older women. Current studies will determine the ability of resistance training to offset these catabolic effects on skeletal muscles of a low‐protein (0.6 g/kg/day) diet prescribed for elderly with chronic renal failure. More long‐term studies of efficacy and feasibility of diet and exercise combinations are needed in the aged to optimize the potential for healthful shifts in body composition.
Recycling and Redox Cycling of Phenolic Antioxidants
Authors: KAGAN V. E. , TYURINA Y. Y.
Published: February 2006

ABSTRACT: Effectiveness of phenolic antioxidants in protecting against oxidative stress depends on their reactivity towards reactive oxygen species and the reactivity of the antioxidant phenoxyl radicals towards critical biomolecules. Reduction of phenoxyl radicals by intracellular reductant (ascorbate, thiols) as well as by enzymes or intermediates of electron transport (e.g., in mitochondria and the endoplasmic reticulum) recycles phenolic antioxidants, thus enhancing antioxidant protection. Several cascades may be involved in physiologically relevant recycling of vitamin E from its phenoxyl radicals. The two major ones are dihydrolipoic acid → (GSH) → ascorbate, and enzymes of electron transport → coenzyme Q. Importantly, phenoxyl radicals of vitamin E are not directly reduced by intracellular thiols. By contrast, a number of natural phenolic compounds that act as very effective scavengers of reactive oxygen species and organic radicals, may generate reactive secondary radicals of antioxidants. These secondary radicals react and modify critical intracellular targets (lipids, proteins, and DNA). As a result, the role of these phenolic compounds as biological antioxidants may be limited because of their ability to cause cyto‐and genotoxic effects. Typical examples are some estrogens and phenolic drugs (e.g., the antitumor drug, etoposide) that can protect lipids but oxidize GSH and protein sulf‐hydryls. Moreover, phenoxyl radicals produced in the course of radical scavenging by some phenolic compounds (e.g., phenol) are capable of oxidizing both proteins and lipids. Hence, reactivity of phenoxyl radicals should be considered as a critical factor in the development of new antioxidant protectants.
The Chemistry and Biological Effects of Flavonoids and Phenolic Acidsa
Authors: CROFT KEVIN D.
Published: February 2006

ABSTRACT: Flavonoids and phenolic acids are widely distributed in higher plants and form part of the human diet. Recent interest in these substances has been stimulated by the potential health benefits arising from the antioxidant activity of these polyphenolic compounds. This review outlines the basic chemistry, biosynthesis, and structure‐activity relationships of these compounds with respect to their antioxidant activity. Although there is considerable in vitro evidence establishing antioxidant activity for polyphenolics found in the diet, there are few studies in humans on the absorption and bioavailability of these compounds. The possible in vivo antioxidant effects of the flavonoids is even less well understood. For example, controlled human intervention studies with beverages, such as red wine, that are rich in polyphenolic compounds, have yielded conflicting results. Our own work and that of others suggests that the final effects of such beverages may be a balance between the well‐described prooxidant effects of alcohol and its metabolism and the antioxidant effects of the polyphenolic constituents. There is a need for further studies to increase our understanding of the absorption and in vivo biological effects of this family of compounds.
The Antioxidant and Biological Properties of the Carotenoidsa
Authors: KRINSKY NORMAN I.
Published: February 2006

ABSTRACT: Much effort has been expended in evaluating the relative antioxidant potency of carotenoid pigments in both in vitro and in vivo experiments. It is quite clear that in vitro, carotenoids can inhibit the propagation of radical‐initiated lipid peroxidation, and thus fulfill the definition of antioxidants.

When it comes to in vivo systems, it has been much more difficult to obtain solid experimental evidence that carotenoids are acting directly as biological antioxidants. In fact, under nonphysiological circumstances, carotenoids may act as prooxidants. These results can be modified by altering the oxidant stress, the cellular or subcellular system, the type of animal, and environmental conditions, such as oxygen tension. Results of this type raise the question as to whether it is still appropriate to group the carotenoids with such antioxidant vitamins as vitamin E and vitamin C. Thus, the biological properties of the carotenoids may be much more related to the products of the interaction of carotenoids with oxidant stress, that is, such breakdown products as apocarotenoids and retinoids.
Structural and Functional Changes in Proteins Induced by Free Radical‐mediated Oxidative Stress and Protective Action of the Antioxidants N‐tert‐Butyl‐α‐phenylnitrone and Vitamin Ea
Authors: BUTTERFIELD D. ALLAN , KOPPAL TANUJA , HOWARD BEVERLY , SUBRAMANIAM RAM , HALL NATHAN , HENSLEY KENNETH , YATIN SERVET , ALLEN KERRY , AKSENOV MICHAEL , AKSENOVA MARINA , CARNEY JOHN
Published: February 2006

ABSTRACT: The free radical theory of aging proposes that reactive oxygen species (ROS) cause oxidative damage over the lifetime of the subject. It is the cumulative and potentially increasing amount of accumulated damage that accounts for the dysfunctions and pathologies seen in normal aging. We have prevously demonstrated that both normal rodent brain aging and normal human brain aging are associated with an increase in oxidative modification of proteins and in changes in plasma membrane lipids. Several lines of investigation indicate that one of the likely sources of ROS is the mitochondria. There is an increase in oxidative damage to the mitochondrial genome in aging and a decreased expression of mitochondrial mRNA in aging. We have used a multidisciplinary approach to the characterization of the changes that occur in aging and in the modeling of brain aging, both in vitro and in vivo. Exposure of rodents to acute normobaric hyperoxia for up to 24 h results in oxidative modifications in cytosolic proteins and loss of activity for the oxidation‐sensitve enzymes glutamine synthetase and creatine kinase. Cytoskeletal protein spin labeling also reveals synaptosomal membrane protein oxidation following hyperoxia. These changes are similar to the changes seen in senescent brains, compared to young adult controls. The antioxidant spin‐trapping compound N‐tert‐butyl‐α‐phenylnitrone (PBN) was effective in preventing all of these changes. In a related study, we characterized the changes in brain protein spin labeling and cytosolic enzyme activity in a series of phenotypically selected senescence‐accelerated mice (SAMP), compared to a resistant line (SAMR1) that was derived from the same original parents. In general, the SAM mice demonstrated greater oxidative changes in brain proteins. In a sequel study, a group of mice from the SAMP8‐sensitive line were compared to the SAMR1‐resistant mice following 14 days of daily PBN treatment at a dose of 30 mg/kg. PBN treatment resulted in an improvement in the cytoskeletal protein labeling toward that of the normal control line (SAMR1). The results of these and related studies indicate that the changes in brain function seen in several different studies may be related to the progressive oxidation of critical brain proteins and lipids. These components may be critical targets for the beneficial effects of gerontotherapeutics both in normal aging and in disease of aging.
Formation of the Placenta and Extraembryonic Membranes
Authors: CROSS JAMES C.
Published: February 2006

ABSTRACT: In eutherian mammals, the first cell types that are specified during embryogenesis are committed to form extraembryonic (placenta and fetal membranes) rather than embryonic structures. The trophoblast cell lineage, for example, forms at the morula‐to‐blastocyst transition: cells at the periphery of the morula become trophoblast, whereas cells on the inside remain undifferentiated embryonic ectoderm, which later gives rise to the fetus as well as the endodermal and mesodermal components of the placenta and extraembryonic membranes. Genetic studies in mice are beginning to identify growth factors and cell adhesion molecules that mediate interactions between cell types that are essential for morphogenesis of the placenta and fetal membranes, as well as transcription factors that control the differentiation of extraembryonic cell types.
Common Molecular Pathways in Skeletal Morphogenesis and Repair
Authors: FERGUSON CRISTIN M. , MICLAU THEODORE , HU DIANE , ALPERN EYTAN , HELMS JILL A.
Published: February 2006

ABSTRACT: The formation of bone is a continual process in vertebrate development, initiated during fetal development and persisting in adulthood in the form of remodeling and repair. The remarkable capacity of skeletal tissues to regenerate has led to the hypothesis that the molecular signaling pathways regulating skeletogenesis are shared during fetal development and adult wound healing. A number of key regulatory pathways that are required for endochondral ossification during fetal development are described, and their reintroduction in fracture repair demonstrated. Secreted proteins such as Sonic and Indian hedgehog exert their effect on pattern formation and chondrogenesis in the appendicular skeleton, partly through regulation of molecules such as bone morphogenic proteins (Bmps) and parathyroid hormone‐related peptide (PTHrP). Once chondrocytes have matured and hypertrophied, they undergo apoptosis and are replaced by bone; the transcription factor Cbfal plays a critical role in this process of chondrocyte differentiation and ossification. Analyses of the expression patterns of these genes during fracture healing strongly suggest that they play equivalent roles in adult wound repair. Knowledge acquired through the study of fetal skeletogenesis will undoubtedly contribute to an understanding of fracture repair, and subsequently guide the development of biologically based therapeutic interventions.
Structural and Genetic Analysis of Laminin‐Nidogen Interaction
Authors: MAYER ULRIKE , KOHFELDT EDDIE , TIMPL RUPERT
Published: February 2006

ABSTRACT: High‐affinity binding of nidogen to laminins involves a single binding site on the laminin γ1 chain and is thus a property shared by almost all laminin isoforms. This binding mediates the connection of laminins to the collagen IV network, perlecan and other proteins and is considered to be an essential step in the stabilization of basement membranes. Nidogen binding has been located to a single LE module (γ1III4) by recombinant analysis. Site‐directed mutagenesis and X‐ray crystallography demonstrated that three amino acids (Asp, Asn, Val) in loop a of γ1III4 are crucial for binding and are supported by some other residues. A restricted complementary binding region seems to exist on nidogen domain G3. A mutant laminin γ1 chain gene that lacks the region encoding γ1III4 was prepared in mouse embryonic stem (ES) cells by homologous recombination. ES cells homozygous for this defect were shown to assemble laminin‐1 into a cruciform structure and to secrete it properly. Yet the mutant laminin failed to associate with nidogen. The mutant ES cells were still able to form embryoid bodies with a similar differentiated histology as the wild type. Immunofluorescence, however, indicated an impaired deposition of nidogen into basement membrane‐like structures.
Modulation of Cell‐Extracellular Matrix Interactionsa
Authors: SECHLER JAN L. , CORBETT SIOBHAN A. , WENK MELISSA B. , SCHWARZBAUER JEAN E.
Published: February 2006

ABSTRACT: Changes in extracellular matrix (ECM) structure and composition, such as occur during morphogenesis, can have important regulatory effects on cell behavior. Two fibronectin (FN)‐based systems have been developed to dissect how cells respond to different types of ECM. One system mimics the provisional matrix of the wound and is composed of FN cross‐linked into a fibrin clot matrix. Unlike cells on FN alone, cells on an FN‐fibrin matrix are smaller with cortical distribution of actin filaments and membrane ruffles. Addition of the ECM protein tenascin to the FN‐fibrin matrix induces a different cell morphology. Thus, matrix composition can have profound effects on cell phenotype. Cells also interact with FN while assembling it into a fibrillar matrix. Using recombinant FNs, a domain that is required for normal progression of FN fibril formation has been identified. During assembly of this recombinant matrix, formation of actin stress fibers and focal adhesions is delayed, demonstrating that changes in FN matrix structure can affect intracellular organization and activation of signaling pathways.
The Significance of Matrix Metalloproteinases during Early Stages of Tumor Progressiona
Authors: LOCHTER ANDRÉ , STERNLICHT MARK D. , WERB ZENA , BISSELL MINA J.
Published: February 2006

ABSTRACT: Matrix metalloproteinases (MMPs) orchestrate tissue remodeling and play diverse roles during organ development. They are produced excessively during the course of various pathological conditions, including solid tumors. An important function of MMPs during tumor progression is to provide the proteolytic activity that is necessary both for tumor cells to invade extracellular matrix (ECM) and for neovascularization of tumor tissue by endothelial cells. Recently, independent studies in transgenic animals suggest that MMPs may, in addition, promote very early stages of tumor progression. To investigate this possibility further, we have analyzed the consequences of MMP overexpression in functionally normal and nontumorigenic mouse mammary epithelial cells in culture. Our observations demonstrate that the MMP stromelysin‐1 (SL‐1) triggers an epigenetic molecular program in mammary epithelial cells that results in a number of phenotypic alterations that eventually culminate in the generation of a malignant tumor‐cell phenotype.
Laminin Isoforms and Epithelial Development
Authors: EKBLOM MARJA , FALK MATS , SALMIVIRTA KATRIINA , DURBEEJ MADELEINE , EKBLOM PETER
Published: February 2006

ABSTRACT: Several different approaches suggest that basement‐membrane assembly is important for epithelial development. Basement membranes contain isoforms of collagen IV, proteoglycans, and noncollagenous glycoproteins such as the laminins and nidogens. The expression and role of laminins for epithelial morphogenesis is reviewed. Laminins are large heterotrimeric proteins composed of α, β, and γ chains. Many major epithelial laminins and their receptors have been identified recently, and, the extracellular protein‐protein interactions that drive basement‐membrane assembly are beginning to be understood. Three laminin α‐chains are typically made by epithelial, α1, α3, and α5. Three major epithelial heterotrimers can at present be distinguished‐laminin‐1 (α1β1γ1), laminin‐5 (α3β3γ2), and laminin‐10 (α5β1γ1)‐but other heterotrimers may exist in epithelia. Laminins containing either α1 or α3 chains are largely limited to epithelia, whereas the α5 is also found in endothelial and muscle basement membranes, particularly in the adult. Some epithelial cell types express several laminin α‐chains, so it is relevant to test how the different laminins affect epithelial cells. Laminins interact with integrin type of receptors on the cell surface, but binding to other proteins has also recently been demonstrated. Two important recent discoveries are the identification of dystroglycan as a major laminin receptor in muscle and epithelia, and nidogen as a high‐affinity laminin‐binding protein important for basement‐membrane assembly. Antibody perturbation experiments suggest these protein‐protein interactions are important for epithelial morphogenesis.
The Future of Biothermal Engineeringa
Authors: CHATO JOHN C. , LEE RAPHAEL C.
Published: February 2006

ABSTRACT: This is a report on a three‐day workshop held at the Allerton House of the University of Illinois. The first day consisted of invited tutorials on topics related to biothermal engineering: biological structures, analysis of microvascular heat transfer, temperature measurement, cryobiology and cryosurgery, burns, and industrial and consumer applications.

The rest of the workshop consisted of discussions in ‘small groups and in plenary sessions dealing with relevant topics. Although the discussions endeavored to be as comprehensive as possible, the specific topics were selected by the participants based on their expertise and interests.

The main areas examined were:

Instrumentation

Priority applications

Mathematical modeling

Thermal injury

The reliable measurement of the temperature distribution inside the living tissue is still the premier problem of instrumentation although the measurement of other parameters, such as properties, blood perfusion or heat flux, is also of great importance.

The most important applications are medical, industrial, consumer, agricultural, space, and military. The degree of sophistication needed in the analysis of specific problems varies a great deal from relatively simple heat conduction models to complicated ones including blood perfusion, anisotropy, and the influence of large blood vessels. For many applications new experimental data are still needed.

There have been significant advances in the modeling of living tissue with increasing understanding of its thermal behavior. The consensus was, however, that the models will always have to be tissue or organ specific and some new models are still to be developed.

A new thermal injury classification for biological systems which has more meaning at the cellular and molecular level is needed to provide predictive value.

Although not all aspects of biothermal engineering were covered, the findings of this workshop give a rather comprehensive overview of the field. It is the strong consensus of the participants that a periodic review of this type is of great benefit not only to the participants but to all workers in this field.
Mathematical Simulation of Heat Transfer Process in Skin Cover at Burn Injury
Authors: ENALEJEV R. Sh. , KACHALKIN W. A.
Published: February 2006

ABSTRACT: The results of an investigation regarding the correlation between contact thermal burns and temperature profile in skin cover of bioobject are given in this work. Simple temperature criterion of burns appearance is determined on the basis of modeling of heat transfer process. The physical model of skin and critical temperature criterion are suggested for estimation of heat protecting properties of material for clothes.
Computer Simulation of Heat and Mass Transfer in Tissue During High‐Intensity Long‐Range Laser Irradiation
Authors: DIRECTOR L. B. , FRID S. E. , MENDELEEV V. YA. , SCOVOROD'KO S. N.
Published: February 2006

ABSTRACT:Three‐dimensional transient finite difference numerical model of the biological tissue irradiated by powerful laser beam is developed. It is used to simulate the thermal behavior of tissue assuming that radiation wavelength is chosen to give rise for volumetric heat sources. A three‐dimensional seven‐flow model is used to calculate radiation propagation. Evaporation and burn‐out of tissue resulting in a through hole along the axis of the beam are taken into account. Besides the water boiling and corresponding changes of thermal and optical tissue properties the model takes into account one of the heat steam transfer mechanisms. Estimates are carried out for the effects of diffusion transfer and vaporization of water from the tissue surface. Kinetics of protein denaturation process are calculated by Arrenius equation. The problem is solved numerically using discrete grid technique and adaptive time‐step control algorithm.
Laser Ultrasonic Transport of Drugs in Living Tissues
Authors: ZHAROV VLADIMIR P. , LATYSHEV ALEXEI S.
Published: February 2006

ABSTRACT: This paper deals with non‐invasive erbium: yttrium aluminium garnet (Er:YAG) laser drug delivery methods, i.e. laser optoacoustic (OA) impregnation, enhanced laser OA impregnation, laser injection, and laser OA injection. Preliminary in vitro experiments on stratum corneum laser ablation, enhanced diffusion, brilliant green laser injection into both gelatinous gel and an autopsy piglet skin, and research on laser OA injection have been conducted. The vacuum suction mechanism of laser drug injection is discussed.
On the Thermal Efficiency of Cold‐Stressed Fingers
Authors: SHITZER AVRAHAM
Published: February 2006

ABSTRACT: Thermal efficiency of cold‐stressed finger‐tips during cold induced vasodilatation (CIVD) is considered. The actual heat loss from the finger‐tip is compared to either the minimal or the maximal heat losses. The actual heat loss is estimated by integrating the area under the time‐temperature curve of the finger‐tip. The minimal heat loss is estimated by extrapolating an exponential approximation of finger‐tip temperature until it reaches a certain minimal value. The value used in this study is 5°C, which is the pain threshold. The maximal heat loss is calculated by assuming finger‐tip temperature to be maintained at its initial value throughout the cold exposure. These quantities were calculated for a series of exposures involving two environmental conditions of gloved subjects: Tdry bulb=− 17.2°C, Tdew point=− 25.1°C (cold‐dry) and Tdry bulb= 0°C, Tdew point= ‐8.4°C (cold‐wet). Thermal efficiency was in the range of 0.40 ‐ 0.85 for the minimal heat loss value (ηmin) and 0.22 ‐ 0.72 for the maximal heat loss value (ηmax). Weak linear relationships between the two definitions of the thermal efficiencies and the total duration of the CIVD phase was indicated. The thermal efficiency based on minimal heat loss indicated an inverse relation with the total duration of the CIVD phase. This contradiction could be reconciled by the application of the common concept of “coefficient of performance”. Considerable inter‐ and intra‐subjects variability was found.
Measurement of Thermal Diffusivity of Bovine Aorta Subject to Finite Deformationa
Authors: DOSS DAVID J. , HUMPHREY JAY D. , WRIGHT NEIL T.
Published: February 2006

ABSTRACT:The flash thermal diffusivity measurement technique is applied to tissue for the first time. Making use of its minimal contact with the specimen, the flash technique is extended to allow for well‐defined, biaxial, finite strain. As an example application, the radial component of thermal diffusivity of bovine descending aorta is measuredin vitroas a function of equibiaxial stretch, at room temperature. Data analysis is accomplished using a Marquardt algorithm coupled with a finite difference solution of the thermal diffusion equation. Extension of this method to measure simultaneously three orthogonal components of diffusivity, at different levels of temperature, is discussed.
The Effect of Turbulent Fluctuation of Air on Thermal Sensation
Authors: SUGAI KIYOMI , MAEKAWA HIROSHI , KOBAYASHI MUTSUO , TAKANO TSUYOSHI , KOMORIYA SATOSHI
Published: February 2006

ABSTRACT: The palm of right hand was alternately exposed to turbulent and laminar flows of air with the same velocity, to investigate the effect of turbulent velocity fluctuation on thermal sensation. It could be quantitatively shown for the first time, by measuring subjective sensations, that the turbulent velocity fluctuation had the effect of causing the air temperature to be felt lower than that of the laminar flow. The results of heat transfer experiments using an aluminum disk as a model of the palm suggested that the difference in thermal sensation for the two air flows was generally ascribable to the difference in heat transfer coefficient from the skin of the palm caused by the turbulent velocity fluctuation. The hypothesis that the temperatures of the turbulent and laminar flows of air with the same velocity would be felt the same when heat loses from the skin to the two air flows were equal, was supported by the results of these experiments.
Structure and Growth of Tumors: The Effect of Cartesian, Cylindrical, and Spherical Geometries
Authors: RIZWAN‐UDDIN  , SAEED IBRAHIM M.
Published: February 2006

ABSTRACT: We present results of numerical simulations of a mathematical model simulating mass transfer in the development of a tumor, resulting in its encapsulation and lobulation. A modified generation term that reflects the population pressure on growth leads to nodular tumor growth. Simulations have been carried out in one dimensional Cartesian, cylindrical, and spherical geometries. Important differences between the three cases have been found. Simulation results in spherical geometry suggest the lobes near the center of the tumor to be larger than those near the capsule wall.
Concentration Polarization of Low Density Lipoproteins (LDL) in the Arterial Systema
Authors: FATOURAEE NASSER , DENG XIAOYAN , DE CHAMPLAIN ALAIN , GUIDOIN ROBERT
Published: February 2006

ABSTRACT: The atherogenic lipid concentration at the luminal surface of a blood vessel may vary according to its location in the arterial tree because of regional differences in wall shear rate, blood pressure, and vascular permeability. We therefore hypothesized that these local variations in the luminal surface lipid concentration may contribute to the localization of atherosclerosis. To verify this hypothesis, the transport of low‐density lipoproteins from flowing blood to the arterial wall was studied numerically under both steady‐state and pulsatile flow conditions. Numerical analysis predicted that “concentration polarization” of LDL may occur in the arterial system under these conditions. In contrast to steady‐state flow conditions, the luminal surface LDL concentration varied with time in a cardiac cycle. However, its time‐average value was slightly higher than the corresponding value under steady‐state flow conditions. The time‐average value of the luminal surface LDL concentration was 5 to 14% greater than the bulk concentration in a straight segment of an artery. The luminal surface LDL concentration at the arterial wall was flow‐dependent, varying linearly with the filtration rate through the vessel wall and inversely with wall shear rate. This may therefore have some significant implications for the pathogenesis and localization of vascular disorders.
A Model Of Low‐Temperature Water Transport For Hepatocyte Spheroidsa
Authors: KORNISKI BRIAN , HUBEL ALLISON
Published: February 2006

ABSTRACT: Spheroids are multicellular aggregates that exhibit a more tissue‐like morphology and function when compared to monolayer cultures of the same cells. Hepatocyte spheroids are presently under investigation for use in an artificial liver. The ability to cryopreserve hepatocyte spheroids is essential for their clinical and commercial application. A multicompartment model was formulated to predict water content as a function of temperature during freezing. The theoretical predictions of water transport indicate that there will be spatial differences in water content of the spheroid during freezing and that due to the rapid decrease in water transport with decreasing temperature, the undercooling of the intracellular solution during freezing will increase steadily. These results indicate that conventional freezing of hepatocyte spheroids will be difficult to accomplish due to transport limitations in the spheroids.
Non‐Linear Microscale Alterations in Membrane Transport by Electropermeabilizationa
Authors: GOWRISHANKAR T. R. , CHEN WEI , LEE RAPHAEL C.
Published: February 2006

ABSTRACT: The purpose of this study was to quantify the changes in cell membrane conductance in response to electropermeabilization, which may elucidate the mechanisms of tissue injury resulting from high‐voltage electrical shock. A high‐speed, space‐clamp and voltage‐clamp experimental configuration was used. The pulse parameters of an imposed transmembrane potential that are instrumental in membrane properties alteration were precisely controlled. The dynamics of the non‐linear electroporation response was characterized.
Things We Do Not Know about Cryopreservation of Biological Organs
Authors: TANASAWA ICHIRO
Published: February 2006

ABSTRACT: This article is intended to summarize the state‐of‐the‐art of cryopreservation of biological organs by raising eight questions to be answered. Brief answers and comments are given to each of the questions. Although they never are sufficient for complete understanding of the phenomena occurring in cryopreservation, they might be useful for letting us know better what we sould do next.
Three‐Dimensional Behavior of Ice Crystals and Biological Cells during Freezing of Cell Suspensionsa
Authors: ISHIGURO HIROSHI , KOIKE KAZUHITO
Published: February 2006

ABSTRACT:Behavior of ice crystals and human red blood cells during extracellular‐freezing was investigated in three‐dimensions using a confocal laser scanning microscope(CLSM), which noninvasively produces tomograms of biological materials. Physiological saline and physiological saline with 2.4M glycerol were used for suspension. Various cooling rates for directional solidification were used for distinctive morphology of the ice crystals. Addition of acridine orange as a fluorescent dye into the cell suspension enabled ice crystal, cells and unfrozen solution to be distinguished by different colors. The results indicate that the microscopic structure is three‐dimensional for flat, cellular, and dendritic solid‐liquid interfaces and that a CLSM is very effective in studying three‐dimensional structure during the freezing of cell suspensions.
A continuous hybrid microwave heating process for producing rapid and uniform rewarming of cryopreserved tissues
Authors: ZHANG QIONG , JACKSON TOM H. , UNGAN AYDIN
Published: February 2006

ABSTRACT: This study investigated use of a continuous hybrid microwave heating process for producing rapid and uniform heating of cryopreserved tissues. This process combines volumetric energy deposition by microwaves with convective surface heating to produce increased warming rates. Moreover, such a combination of heating techniques introduces additional parameters which can be varied in order to obtain better control of the heating process. In order to evaluate the effectiveness of a continuous hybrid heating scheme, a numerical simulation was developed which solved for electric and temperature fields within a microwave resonant cavity containing beef tissue. The simulation accounted for the temperature dependence of cryopreserved tissue's dielectric properties through an iterative scheme which can simulate thermal runaway. The simulation indicated that a continuous hybrid heating heating process could produce uniform warming at rates which would be unobtainable by conventional microwave heating.
Effects on Rapid Cooling of Small Samples in Quenchinga
Authors: CAO QIAN , HUA TSE‐CHAO
Published: February 2006

ABSTRACT: Rapid cooling of small samples is necessary both to cryofixation for electron microscopy and to vitrification for cryopreservation. Several effects on the cooling rates of small samples quenched into liquid nitrogen were studied, including the diameter of samples, the subcooling of liquid nitrogen, the quenching speed, and the quenching distance. The heat flux is up to 1.4 × 106 W/m2; the cooling rate is also up to 8200 K/s at the CHF point of boiling curves for sphere of diameter 0.287 mm quenching into subcooled liquid nitrogen. It is also found that if the time of sample moving inside the liquid nitrogen is not longer than the time required for forming stable vapor in the liquid, the quenching boiling heat transfer is not influenced by the quenching speed. Several equations for calculating heat flux of samples are also presented.
Cryopreservation and Transplantation of Dog Tracheaa
Authors: ZHAO HENG , HUA TSE‐CHAO , ZHOU YUN‐ZHONG , WANG QI‐FENG , YANG YI , BAO LI‐LI
Published: February 2006

ABSTRACT: In order to meet the need of trachea transplantation for clinical application, it is important to research the methods of cryopreservation and transplantation of trachea, By the thermal analyses and thermal control techniques, combined with electron microscopy, the effects of cooling and warming rates with different concentrations of cryoprotective agents were studied. Also the transplantation technique was studied, eighty five percent (17/20) of the dogs were survival after the transplantation with cryopreserved tracheas.
Biophysics Of Freezing In Liver Of The Freeze‐Tolerant Wood Frog, R. Sylvaticaa
Authors: BARRAT PAUL R. , DEVIREDDY RAMACHANDRA V. , STOREY KENNETH B. , BISCHOF JOHN C.
Published: February 2006

ABSTRACT: This study investigates the water transport characteristics during freezing in the liver tissue of the freezetolerant wood frog Rana sylvatica. Experiments were performed using both low temperature microscopy and a differential scanning calorimeter (DSC). Tissue samples were cooled at 2 and 5°C/min by a “two‐step” freezing technique to end temperatures of ‐4, ‐6, ‐8, ‐10, and ‐20°C, followed by a slam cooling (>1000°C/min) step. Stereological analysis of the low temperature microscopy results leads to the conclusions that 74% of the control tissue is cellular (26% vascular), Vb (osmotically inactive cell volume) is 0.4Vo and the Krogh cylinder dimensions are: distance between adjacent sinusoid centers, ΔX = 64 μm, original sinusoid (vascular) radius, rvo= 18.4 μm and length of the Krogh cylinder, L = 0.71 μm (assuming a single isolated hepatocyte cell diameter of 16 μm). A parallel study was also done using the DSC at 2 and 5°C/min, and the measured heat releases from the tissue were used to calculate water transport data. Both techniques confirmed that tissue cooled at 5°C/min does not dehydrate completely, but does so when cooled at 2°C/min. By curve fitting a model to 5°C/rain water transport data from both techniques the biophysical parameters of water transport were obtained: Lpg = 1.76 μm/min‐atm and ELp = 75.5 Kcal/mol. A modified Krogh model was used to account for the fact that ∼24% of the hepatocytes were found not to be in direct contact with the vasculature. This model was then used to explain the experimentally measured water retention in some cells on the basis of different volumetric responses to dehydration of cells directly adjacent to vascular spaces and cells at least one cell removed from the vascular spaces.