bluuebunny/crossref_metadata_2025 huggingface dataset:
Worker Produced Health Education Material for the Construction Trades
Authors: Roter Debra L. , Rudd Rima E. , Keogh James , Robinson Betty
Published: April 2008

There is broad acceptance of the philosophic foundations of health education as grounded in the collaborative model of client and professional partnership. In practice. however, this partnership is largely dominated by the professional side. Workers may be particularly sensitive to professional domination as issues associated with health promotion vs. safety and health programs at the workplace are often politicized. This polarization is particularly evident in the area of asbestos-related hazard prevention, reduction, and education. Using asbestos hazards as the unifying theme, we participated in a program to facilitate active participation of workers in the production of their own occupational health education materials through the use of the photonovel. Representatives from some seven building trade locals worked with a staff to produce a twenty-four-page photonovel for their co-workers. A random sample of 500 members of building trades locals received either a copy of the photonovel or a popular NCI asbestos pamphlet with an evaluation questionnaire. Differences between the groups were evident in favor of the photonovel in readability, factual recall, general credibility, and attitudes toward future involvement in health and safety issues.
Using the Arts and Literature in Health Education
Authors: McDonald Marian , Antunez Giovanni , Gottemoeller Megan
Published: April 2008

The article explores and defines how the arts and literature can be used to advance health education. The authors examine the historical role of the arts and literature in social change, and more recently in educational and clinical settings. The use of the arts and literature in health education is examined in relationship to health education theory. Six ways the arts and literature can be utilized in health education practice are delineated, with numerous recent examples. The authors discuss the growing body of health promotion experience which draws on cultural vehicles, including examples of evaluated programs. The authors discuss the relevance of the arts and literature for health education in urban settings, arguing that the arts can serve to promote diversity and build unity. The article concludes with lessons from using the arts to conduct community assessment in a Latino community in metropolitan New Orleans.
Comparing Powerpoint Experts' and University Students' Opinions about Powerpoint Presentations
Authors: MacKiewicz Jo
Published: April 2008

Technical communication instructors want to help students, as well as professionals, design effective PowerPoint presentations. Toward this end, I compare the advice of academic and industry experts about effective PowerPoint presentation design to survey responses from university students about slide text, visual elements, animations, and other issues related to PowerPoint presentation design and delivery. Based on this comparison, I suggest some topics, such as PowerPoint's Slide Sorter view, that technical communication instructors and other presentation instructors might address when they cover presentations in their classes or seminars.
Scientific and Pragmatic Challenges for Bridging Education and Neuroscience
Authors: Varma Sashank , McCandliss Bruce D. , Schwartz Daniel L.
Published: April 2008

Educational neuroscience is an emerging effort to integrate neuroscience methods, particularly functional neuroimaging, with behavioral methods to address issues of learning and instruction. This article consolidates common concerns about connecting education and neuroscience. One set of concerns is scientific: in-principle differences in methods, data, theory, and philosophy. The other set of concerns is pragmatic: considerations of costs, timing, locus of control, and likely payoffs. The authors first articulate the concerns and then revisit them, reinterpreting them as potential opportunities. They also provide instances of neuroscience findings and methods that are relevant to education. The goal is to offer education researchers a window into contemporary neuroscience to prepare them to think more specifically about the prospects of educational neuroscience.
An Ecology Metaphor for Educational Policy Analysis: A Call to Complexity
Authors: Weaver-Hightower Marcus B.
Published: April 2008

Educational policy might productively be conceptualized with an ecology metaphor. Each policy, thus considered, exists within a complex system that reflects varied international, national, regional, and local dynamics. Using this metaphor provides policy analysts with a view of the regularities and irregularities of any policy, its process, its texts, its reception, and its degree of implementation. The characteristics of policy ecologies alert analysts to the possibilities of great transformation, for good or ill, and give them a way to conceptualize how such transformations occur. Perhaps most important, using an ecology metaphor suggests specific ways that progressive researchers might positively intervene in the policy process.
Standard Errors of Equating for the Percentile Rank–Based Equipercentile Equating With Log-Linear Presmoothing
Authors: Wang Tianyou
Published: April 2008

Holland and colleagues derived a formula for analytical standard error of equating using the δ-method for the kernel equating method. Extending their derivation, this article derives an analytical standard error of equating procedure for the conventional percentile rank–based equipercentile equating with log-linear smoothing. This procedure is illustrated with real test data and is evaluated using both the bootstrap and the parametric bootstrap (simulation) methods for three different equating designs.
The Mean Filtration Pressure of Leukocyte Suspensions and Its Relation to the Passage of Leukocytes through Nuclepore Filters and Capillary Networks
Authors: EPPIHIMER M. J. , LIPOWSKY H. H.
Published: April 2008

Objective: To quantitatively evaluate the deformability of bulk suspensions of leukocytes (WBCs), account for the variance of individual cell mechanical properties, and deduce the potential for WBC entrapment within the capillary network in response to alterations in cell properties.

Methods: The transient washout of WBCs initially trapped under low perfusion pressure in 5‐μm pores of Nuclepore filters was analyzed for a 0.2‐ml bolus of WBCs (derived from hamsters) with equal numbers of filter pores and cells, to characterize the statistical distribution of pressures, pyield, required to dislodge the cells. Contributions of the variance in WBC diameter, pore diameter, and cremaster muscle capillary diameter to pyield were estimated with a WBC cortical shell model and an analysis of the probability function of the ratio of WBC to pore diameter, Λ.

Results: For normal WBCs, pyield exhibited a log‐normal distribution with mean ((pyield)) of 0.59 cmH2O. Incubation of cells in cytochalasin‐B reduced (pyield) almost 50%, whereas phorbol myristate acetate increased (pyield) twofold. Incubation in N‐formyl‐methiolnyl‐leucyl‐phenylalanine had no significant effect on (pyield), as polymorphonuclear cells became permanently trapped in the filter. The fluorescent dyes acridine orange, acridine red, and tetramethylrhodamine isothiocyanate increased (pyield) as much as 10‐fold, whereas steady‐flow filtration methods showed no alteration. Analysis of the distribution of Λ revealed that due to their smaller pore diameters, in vitro filtration methods may overestimate in vivo values of (pyield) by almost twofold.

Conclusions: The transient filtration of WBC suspensions appears to be much more sensitive to subtle alterations in WBC deformability than steady‐flow methods and may provide greater insight into the determinants of capillary perfusion. Estimates of (pyield) are comparable to those obtained with micropipettes and permit analysis of substantially greater numbers of cells within a sample. Fluorescence labeling techniques should be used with caution, as they may dramatically alter cell properties to an extent undetectable by direct in vivo observations.
An Adenosine Agonist Increases Blood Flow and Density of Capillary Branches in the Optic Tectum of Xenopus laevis Tadpoles
Authors: Jen Shyian Charcha , Rovainen Carl M.
Published: April 2008

Objective: To test the hypothesis that adenosine can increase capillary densities in developing brain tissue.

Methods: Transparent tadpoles of albino Xenopus laevis were exposed to adenosine agonists, mainly 5′‐N‐ethylcarboxamidoadenosine (NECA), and to antagonists, mainly 8‐phenyltheophylline (8PT) in aquarium water. After 2 weeks in drugs, networks of blood vessels on the dorsal surface of the optic tectum were scanned in vivo by videomicroscopy. Densities of surface capillaries and venules, of deep branches, and of deep perfused capillaries were calculated.

Results: NECA initially dilated brain blood vessels and chronically increased blood flow by a simple subjective index. 8PT diminished diameters and prevented the subjective flow increase. Chronic 3 μM NECA significantly increased densities of total deep branches from pial vessels into the tectum.

Conclusions: In an in vivo amphibian assay, NECA dilated brain capillaries and venules and increased their flow and density. Adenosine was present chemically and increased during metabolic stress. These results are consistent with adenosine as a metabolic signal for growth of blood vessels during brain development. In addition, it appeared that short‐term dilation and flow increase in tectal capillaries in acute NECA was followed over a period of weeks in chronic NECA by vascular remodeling and return of diameters to normal.
Fluid Flow Modulates Vascular Endothelial Cytosolic Calcium Responses to Adenine Nucleotides
Authors: Shen Jian , Luscinskas Francis W. , Gimbrone Michael A , Dewey C. Forbes
Published: April 2008

Objective: To determine whether fluid flow influences the action of soluble vasoactive agonists on vascular endothelium.

Methods: Confluent monolayers of bovine aortic endothelial cells (BAEC) were cultured on glass coverslips, prelabeled with the Ca2+‐sensitive dye fura‐2, and placed in a parallel‐plate flow chamber designed to generate defined laminar fluid flow. Cytosolic free Ca2+ concentration ([Ca2+];) in individual BAEC was monitored during perfusion with medium containing adenine nucleotide under defined flow conditions.

Results: Continuous perfusion with ATP (0.3–3.0 μM) or ADP (0.1–1.0 μM) evoked repetitive oscillations in [Ca2+]; in individual BAEC. The frequency of the [Ca2+]; oscillations was dependent on both nucleotide concentration and levels of applied shear stress; at constant bulk concentration of nucleotide, the frequency increased with shear stress. Stopping flow in the continuous presence of agonists immediately extinguished the oscillatory response. Elimination of extracellular Ca2+ did not inhibit the [Ca2+]; oscillations. In the presence of nonhydrolyzable nucleotide analog, ATPγS or ADPβS, application of flow resulted in similar shear‐dependent [Ca2+]; oscillations, suggesting that flow modulation of the [Ca2+]; response was not simply due to depletion of ATP or ADP in the vicinity of BAEC monolayers as a result of hydrolysis of nucleotides by ectonucleotidases.

Conclusions: These findings suggest that local hemodynamic conditions may modulate the action of vasoactive agents on the vascular endothelium in vivo.
Acidic Fibroblast Factor Induction of Cyclooxygenase II in Rabbit Cardiac Muscle Microvessel Endothelial Cells: Mediation by Protein Kinase C
Authors: Moatter Tariq , Gerritsen Mary E.
Published: April 2008

Objective: To determine if the novel cyclooxygenase, COX II, was induced by acidic fibroblast growth factor (aFGF) in rabbit cardiac muscle microvessel (RCME) endothelial cells and to determine the role of protein kinase C (PKC) activation in the mediation of the aFGF induction of COX activity.

Methods: Cultured RCME cells were treated with aFGF (200 ng/ml). Induction of COX II activity was assessed by determination of COX activity (PGE2 production), by immunoprecipitation of metabolically labeled COX II, and by Northern analyses. The role of PKC was assessed using phorbol myristate acetate and PKC inhibitors and by determination of PKC activity in cytosol and membrane fractions of RCME cells treated with aFGF and phorbol myristate acetate.

Results: aFGF selectively induced COX II protein and mRNA. Protein kinase C activation was implicated in the transduction of the effects of aFGF for the following reasons: (1) phorbol myristate acetate (PMA), a direct activator of protein kinase C, was a potent inducer of COX II mRNA, COX activity and synthesis of COX II protein. (2) H‐7, an inhibitor of PKC, but not the inactive control, HA‐1004, blocked aFGF induction of COX II mRNA, COX II protein synthesis, and COX activity. Two additional inhibitors of PKC, calphostin C and staurosporine, also inhibited aFGF induction of COX activity. (3) Downregulation of PKC by overnight incubation with 1 μM PMA blocked subsequent induction of COX II protein synthesis by aFGF. (4) aFGF treatment of RCME cells resulted in the translocation of PKC activity from the cytosol to the membrane fraction. However, aFGF, at concentrations that elicited COX II, neither induced Ca2+ mobilization from intracellular stores nor increased the accumulation of inositol phosphates.

Conclusion: aFGF induces COX II in RCME and this response in mediated, at least in part, by protein kinase C activation. However, aFGF mediated activation of PKC activation must stimulate this kinase through a pathway of signal transduction distinct from inositol phospholipid accumulation or elevation of intracellular Ca2+.
Desensitization of 5HT2 Receptors by Protein Kinase C Activation in Distal Pulmonary Vascular Smooth Muscle Cells in Culture
Authors: Weng Weili , Reynolds Ian J. , Jani Jitesh P. , Blaskovich Michelle , Sebti Said M. , Davies Paul , Pitt Bruce R.
Published: April 2008

Objective: Although acute and chronic roles of microvascular smooth muscle cells as effectors of pulmonary vascular resistance and remodeling are well appreciated, relatively little is known regarding the direct effects of neurohumoral agents on these cells. We recently reported that microvascular smooth muscle cells isolated from distal rat lung (RPC) express mRNA and binding sites for 5HT2 receptors. The objective of the current study was to determine if protein kinase C (PKC) affected 5HT‐induced changes in intracellular calcium and phosphoinositide metabolism in RPC.

Methods: 5HT‐induced changes in intracellular calcium ([Ca2+]i) in single RPC were determined microspectrofluorometrically using the calcium‐sensitive dye, Fura‐2.

Results: Phorbol 12‐myristate 13‐acetate (PMA: 100 nM) caused a rapid desensitization of 5HT‐induced increases in [Ca2+]i. Staurosporine, a putative PKC inhibitor, abolished the PMA‐induced desensitization. Downregulation of PKC with prolonged (24 hr) PMA exposure also abolished subsequent PMA‐induced desensitization of 5HT response. Neither short‐ nor long‐term exposure of RPC to PMA affected binding of [125I]LSD. Activation of PKC by PMA was associated, however, with complete inhibition of 5HT‐induced increases in intracellular inositol monophosphate.

Conclusions: These data are consistent with PKC causing desensitization of 5HT2 receptors by affecting elements of signal transduction and uncoupling receptor‐G protein complex from phospholipase C in RPC.
Cellular Aspects of Transvascular Exchange: A 40‐Year Perspective
Authors: Renkin Eugene M.
Published: April 2008

Study of the microcirculation began with microscopic anatomy in the 17th century, but it was not until the mid‐19th century that the concept of microcirculatory exchange was developed, in association with the great expansion in knowledge of physical chemistry and cell biology. In the first half of the 20th century, the roles of diffusion and osmosis (ultrafiltration) were put on a quantitative foundation and the physiological basis for regulation of the microcirculation was established. During the past 40 years, our understanding of transvascular exchange has been deepened and widened through two major developments: 1) the application of electron microscopy to the study of microvascular structure and 2) the use of sophisticated physical and mathematical models of passive transport processes to analyze and interpret experimental data. In the past few years, the focus of microvascular research has been returning to cell biology and the role of endothelial cells in controlling transvascular exchange. The 21st century holds promise of many exciting new developments.
Ischemia/Reperfusion‐Induced Granulocyte Influx is a Multistep Process Mediated by Mast Cells
Authors: Kanwar Samina , Kubes Paul
Published: April 2008

Objective: The influx of polymorphonuclear leukocytes (PMNs) that occurs at the onset of reperfusion of postischemic tissue is a multistep mechanism that includes initial rolling of PMNs, a progressive reduction in PMN rolling velocity, and ultimately PMN adhesion and emigration. In this study we assessed whether mast cells play a role in reperfusion‐induced PMN recruitment with emphasis on PMN rolling, adhesion, and emigration.

Methods: Cat small intestinal venules were visualized using intravital microscopy during control, 60 min of ischemia (intestinal blood flow 20% of control), and 60 min of reperfusion in untreated and cromolyn‐ (mast cell stabilizer) pretreated animals.

Results: Between 1 and 5 min of reperfusion, there was a very dramatic rise in PMN rolling which persisted for the next 60 min. In cromolyn‐pretreated animals, the flux of rolling PMNs increased in the very early (5 min) reperfusion period, but by 10 min the number of rolling leukocytes was significantly reduced, an event that persisted for the next 60 min. PMNs rolled at a velocity of 40% of control values for the first 10 min of reperfusion without a change in hemodynamic values but returned toward control values by 60 min of reperfusion. An identical velocity profile was observed for the cromolyn‐treated animals. In untreated animals, PMN adhesion and emigration was significantly increased throughout the reperfusion period, whereas the cromolyn‐pretreated animals had reduced adhesion (60 min of reperfusion) and a reduced rate of emigration throughout the reperfusion period.

Conclusions: Interstitial mast cells contribute significantly to the multistep recruitment (rolling, adhesion, and emigration) of PMNs from blood to postischemic tissues and raise the possibility that antiallergy agents such as cromolyn may be a useful form of therapy in the postischemic intestine.
The Influence of Flow and Hematocrit on the Laser Doppler Flux Signal from the Surface of the Perfused Pig Liver
Authors: WHEATLEY ANTHONY M. , HICKMAN ROSEMARY
Published: April 2008

Objective: We tested the hypothesis that the measurement volume of the laser Doppler flowmeter (LDF) is too small to provide reliable quantitative estimates of total liver blood flow of large mammals, such as the pig.

Methods: In a perfused pig liver, the influence of changing (i) hepatic arterial (HA) and portal venous flows individually (n = 9), (ii) HA flow at fixed portal venous flow (50%, 70%, and 100% expected total liver blood flow), and (iii) hematocrit (0–30%) at fixed total liver blood flow on LDF flux was tested (n = 8).

Results: Linearity of LDF with hepatic arterial flow and portal venous flow was confirmed; however, the slope of the regression lines was higher for hepatic artery [1.92 ± 0.60 (SD)] than portal vein perfused livers (0.66 ± 0.34; P < 0.001). With portal venous flow at 50% and 70% total liver blood flow, changing hepatic arterial flow produced linear LDF versus flow responses, but at 100% total liver blood flow, linearity was achieved in only 6/9 livers. The coefficient of variation for the slopes of regression lines was always > 30%. At constant total liver blood flow (100 ml/min per 100 g), LDF response decreased linearly by a factor of about 2 on changing the hematocrit from 30% to 5% and markedly fell as the hematocrit was further decreased to zero.

Conclusions: These results suggest that (i) the LDF flux signal from the liver surface provides a poor measure of hepatic microcirculatory blood flow during changes in total liver blood flow as the LDF responds with about three times greater sensitivity to changes in hepatic arterial than in portal venous flow, and (ii) when hematocrit is falling, LDF may underestimate hepatic perfusion to a significant extent. In addition, due to high measurement variability, the LDF flux signal cannot be quantified in absolute perfusion units.
Nitric Oxide Mediates C5a‐Induced Vasodilation in the Small Intestine
Authors: LUO HONG Y. , WEAD WILLIAM B. , YANG SAI , WILSON MARK A. , Harris Patrick D.
Published: April 2008

Objective: This study was designed to investigate the microvascular responses of the small intestine to complement C5a and to define the role of nitric oxide in the C5a‐induced response.

Methods: Male Sprague–Dawley rats were anesthetized with pentobarbital, and a loop of small intestine was exteriorized and suffused with Krebs solution. The diameters of large and small arterioles of the small intestinal wall were measured with in vivo videomicroscopy following the application of experimental mediators. Four 1‐hr C5a dose‐response trials were performed (10−14 M, 10−12 M, 10−10 M, and 10−8 M). Then, we completed acetylcholine dose‐response curves with and without Nω‐nitro‐L‐arginine (N‐Arg) to document the adequacy of nitric oxide synthase inhibition. The microvascular response to the topical application of C5a (10−12 M) was recorded in the presence of 2 × 10−4 M N‐Arg. Additionally, experiments of C5a‐induced response with N‐Arg were repeated in the presence of L‐arginine (L‐Arg; the precursor of nitric oxide synthesis) or with systemic administration of superoxide dismutase (SOD).

Results: (1) C5a induces a dose‐dependent vasodilation in the small intestine, and the maximal vasodilation occurs in A3 arterioles at C5a concentration of 10−12 M; (2) N‐Arg inhibits the Ach‐induced vasodilation in the rat small intestine; and (3) L‐Arg or SOD partially reverses the inhibitory effect of N‐Arg.

Conclusions: Nitric oxide mediates the C5a‐induced vasodilation in small intestinal microvessels. Superoxide is, at least partially, responsible for the vasoconstrictor response to C5a in the presence of N‐Arg.
Gene‐Targeted Mice in Leukocyte Adhesion Research
Authors: LEY KLAUS
Published: April 2008

Physiologic and inflammatory leukocyte trafficking are controlled by adhesion molecules on leukocytes and endothelial cells. These adhesion molecules can be grouped into four major families: integrins, immunoglobulinlike molecules, selectins, and glycoproteins serving as selectin ligands. The recent advent of gene‐targeting technology in embryonal stem cells has prompted the production of mutant mice that lack individual adhesion molecules or combinations thereof. Such gene‐targeted mice permit studies into the roles of adhesion molecules in acute and chronic inflammation and of the regulation and interplay between different sets of adhesion receptors in vivo. Microcirculatory studies have been indispensable to our understanding of the importance of certain adhesion molecules for different steps of leukocyte recruitment in vivo. Targeting new genes and investigating mice with combined adhesion‐molecule deficiencies will help to further clarify the molecular mechanisms of leukocyte trafficking in health and disease. This article reviews the insight gained through using adhesion molecule‐deficient mice, emphasizing the role of microcirculatory studies in this research.
Activation‐Dependent Isolation and Culture of Murine Pulmonary Microvascular Endothelium
Authors: GERRITSEN MARY E. , SHEN CHIEN‐PING , MCHUGH MARK C. , ATKINSON WILLIAM J. , KIELY JEANNE‐MARIE , MILSTONE DAVID S. , LUSCINSKAS FRANCIS W. , GIMBRONE MICHAEL A.
Published: April 2008

Objective: Establish a reproducible method for the isolation and cultivation of murine pulmonary microvascular endothelium. To this end, we exploited the localized pattern of microvascular endothelial activation induced in vivo by inflammatory stimuli to isolate a subpopulation of endothelium for in vitro study.

Methods: Immunohistochemical analyses of the pulmonary vasculature of mice treated systemically with gram‐negative bacterial endotoxin (LPS) demonstrated selective expression of VCAM‐1 (CD106) in the endothelial lining of small collecting veins, venules, septal capillaries, and, infrequently, small arteries, which was not observed in control mice. Single cell suspensions prepared by enzymatic dissociation of peripheral lobular tissues dissected from the lungs of LPS‐stimulated mice were incubated with a phycoerythrin‐conjugated antimouse VCAM‐1 monoclonal antibody (MK 1.91). Cells expressing this antigen were isolated by sterile fluorescence‐activated cell sorting (FACS). Positive cell populations were collected and cultured for 1–2 weeks. When confluent, these primary cultures were further FACS enriched for endothelium, positively selecting for cells incorporating a fluorescent derivative of acetylated low density lipoprotein (Di‐I‐Ac‐LDL).

Results: The resulting population of cells (mouse lung endothelial cells, MLEC) were uniformly positive for the endothelial markers von Willebrand factor, thrombomodulin, and Dil‐Ac‐LDL uptake. MLEC readily formed tube‐like structures when cultured on Matrigel and spontaneously demonstrated a sprouting phenotype on fibronectin or collagen matrices. MLEC retained responsiveness to cytokines (IL‐1α, IL‐1β, TNFα, IFNγ) up to at least eight passages from primary culture and demonstrated upregulation of E‐selectin (CD62E) and P‐selectin (CD62P) mRNA as early as 2 hr after LPS stimulation. Characteristic temporal expression patterns of cell surface E‐selectin (maximal at 4 hr and declining toward baseline by 24 hr), VCAM‐1 (maximal at 6–8 hr and remaining elevated for 24–48 hr), and ICAM‐1 (maximal at 6–8 hr and maintained at 24 hr) were observed when cultured MLEC were treated with recombinant murine TNFα or recombinant human (rh) IL‐1α or rhIL‐1β. The rolling, adhesion, and transmigration of human polymorphonuclear leukocytes was markedly increased on cytokine‐activated MLEC monolayers under defined flow conditions.

Conclusion: The strategy of activation‐dependent isolation allows for the reproducible selection of a specific subset of microvascular endothelial cells for in vitro
Pulmonary Microvascular Pressure Profile During Development of Hydrostatic Edema
Authors: NEGRINI DANIELA
Published: April 2008

Objective: To measure, in intact closed chest, the pressure in the pulmonary microvasculature during transition to mild interstitial edema.

Methods: In anesthetized spontaneously breathing rabbits, the pulmonary artery and left atrium were cannulated. Pleural windows were prepared to view the superficial pulmonary microvascular network through the intact parietal pleura. After intravenous infusion of 96.4 ± 12.3 ml of saline at a rate of 0.5 ml/kg h, the hydraulic pressure in the pulmonary microvessels (15–240 μm in diameter) were measured using glass pipettes driven through the pleural window and connected to a servonull system.

Results: After saline, plasma protein concentration decreased from 6 ± 1 to 4.8 ± 0.5 g/dl; pulmonary arterial and left atrial pressures averaged 22.3 ± 6.4 and 2.3 ± 2 cm H2O in control and 23.1 ± 4.2 and 4.2 ± 2 cm H2O after infusion. After saline loading, 16.4% of total pressure drop occurred from pulmonary artery to 80‐μm arterioles, 60.3% in 30–80‐μm arterioles, 6.9% from 30‐μm arterioles to 30‐μm venules and 16.4% in the downstream segment.

Conclusions: Mild interstitial edema induced, with respect to control, constriction of small arterioles and capillary recruitment to maintain a low capillary pressure. Hence, in initial edema, pulmonary circulation prevents further fluid filtration, acting like an intrinsic safety factor to delay development of severe edema.
Heterogeneity of Red Blood Cell Velocity in Skeletal Muscle Decreases with Increased Flow
Authors: TYML KAREL , CHENG LINONG
Published: April 2008

Objective: Effective material exchange between blood and tissue depends on the heterogeneity of microvascular flow. The objective was to address inconsistencies between intravital studies regarding this dependency. We tested the hypothesis that heterogeneity of red blood cell velocity (VRBC) in capillary beds varies with the strength of metabolic stimulus and with capillary bed geometry.

Methods: We used videomicroscopy to measure VRBC in a bed of 10–24 capillaries at the surface of extensor digitorum longus (EDL) muscle in anesthetized rats. The coefficient of variation (CV = standard deviation/mean; an index of spatial heterogeneity) was computed in the same bed before and after (i) 1, 2, 4, or 8 Hz supramaximal muscle contraction or (ii) adenosine superfusion (10−7–10−3 M). Beds with or without arteriolar—venular capillary shunts were used.

Results: Although control VRBC differed between beds (shunt: 232 μm/s; no shunt: 130 μm/s), the percentage increases in postcontraction VRBC did not (range: 111–326%). In both beds, control CV varied greatly (overall range: 28–117%) and 2–8 Hz muscle contractions reduced CV significantly by 25%. Similar results were obtained for adenosine. In confirmatory experiments using the rat cremaster muscle, contractions (4 Hz) and adenosine (10−4 M) also reduced CV. Based on all data, CV = 63–0.022 VRBC (r = 0.82, P < 0.001).

Conclusions: The heterogeneity of VRBC decreased with metabolic stress, regardless of capillary bed geometry. We propose that both the large variability in control CV and the relatively shallow dependence of CV on velocity could be responsible for the present inconsistencies between intravital studies.
Microvascular Architecture and Exchange in Synovial Joints
Authors: LEVICK J. R.
Published: April 2008

The microcirculation of the synovial lining of joints displays many fascinating adaptations to function. One primary function is to supply nutrients to the avascular cartilage, whose chondrocytes are metabolically active but are relatively vast distances from the nearest capillary (> 1 cm in the center of a human knee). Exchange is facilitated by a high density of fenestrated capillaries situated very close to the synovial surface (an arrangement disrupted in rheumatoid synovium) with fenestrations preferentially oriented toward the joint cavity. Even so, diffusion alone is too slow to supply central chondrocytes with glucose. The problem is solved by the synovial microcirculation generating intra‐articular fluid (synovial fluid) that transports glucose by convection during joint movement. Synovial fluid is a plasma ultrafiltrate into which hyaluronan has been secreted, and it also serves to lubricate the joint.

The joint cavity offers unusually easy access to the interstitial side of the microcirculation because the synovial cell layer is discontinuous, with an interstitial matrix between capillary and joint cavity. This allows the experimental study of the effect of the extravascular Starling “forces” (hydraulic and colloid osmotic pressure) on fluid exchange. One unexpected outcome has been the finding that a substantial part of the hydraulic resistance to fluid transport between blood and joint cavity resides in the series interstitial layer rather than in the capillary wall. Another is that, under appropriate boundary conditions (joint angle, etc.) fluid can simultaneously filter into the cavity in some regions (synovium directly overlying capillaries) and out of the cavity into subsynovium in other regions (synovium in the mesh space between capillaries) to produce a turnover of synovial fluid.
Autoradiographic Assessment of Blood Flow Heterogeneity in the Hamster Heart
Authors: STAPLETON DWIGHT D. , MOFFETT TYLER C. , RASKIN DENIS G. , BASSINGTHWAIGHTE JAMES B.
Published: April 2008

Objective: Provide regional flow measurement in the hearts of small mammals using a new, higher‐resolution technique based on the deposition of a molecular marker.

Methods: We determined the instantaneous extraction and retention of the “molecular microsphere” radiolabeled desmethylimipramine in retrogradely perfused hamster hearts. In a separate series of experiments, autoradiography was used to measure regional myocardial deposition densities in hamster hearts of about 0.5 g with spatial area resolution of 16 × 16 μm.

Results: Radiolabeled desmethylimipramine is almost 100% extracted during a single transcapillary passage and is retained in the tissue for many minutes. Autoradiographic images demonstrated a spatial flow heterogeneity with standard deviations of 31 ± 4% of the mean flow (N = 5) in 16 × 16 × 20‐μm3 voxels. This is equivalent to the projections made using fractal relationships from cruder observations obtained with microspheres in the hearts of baboons, sheep, and rabbits.

Conclusion: Autoradiography using a molecular deposition marker provides quantitative information on myocardial flow heterogeneities with resolution at the size of cardiac myocytes. Because the regions resolved are smaller than the volume of regions supplied by single arterioles, the results must slightly exaggerate the true heterogeneity of regional flows.
The Role of Mechanical Stresses in Microvascular Remodeling
Authors: Skalak Thomas C. , Price Richard J.
Published: April 2008

The microvasculature is an extremely adaptable structure that is capable of architectural and functional adjustments in response to multiple biochemical and mechanical stimuli. Inadequate or inappropriate adjustments often result in pathophysiology. Recent work has brought increasing recognition of the importance of microvascular remodeling in widespread disease states such as hypertension, tumor growth, diabetes, and progressive coronary artery occlusion. Much work has been done to characterize the cells and molecules with putative roles in microvascular remodeling, but little is known regarding the mechanotransduction processes that might link hemodynamic stresses such as wall shear stress and circumferential wall stress to structural and functional changes in vivo. Two primary approaches have been employed: in vitro studies that use cultured cells and allow molecular biologic analysis of signaling pathways and gene expression; and in vivo experiments aimed at understanding vessel adaptations in the intact tissue. This article reviews the structural adaptations exhibited by microvessels and the information available from in vitro and in vivo approaches. The formation of new arterioles in intact tissues is examined in detail as an example of integrative work, and the prospects for new technologies are discussed. This is a time of great opportunity for bidirectional exchange between basic in vitro advances and in vivo experimentation. This exchange will be essential in generating new understanding of the role of mechanical stresses in microvascular remodeling.
Conservation of Flow Demonstrated Using the Two‐Slit Velocimeter and Cross Correlator in Epiilluminated Surface Microvessels of the Mouse Brain
Authors: Rosenblum William I.
Published: April 2008

Objective: To validate the use of two‐slit velocimetry in an epiilluminated microvascular bed by demonstrating conservation of flow and to compare this validation with that provided by the literature for transilluminated beds.

Methods: The brain surface vessels of mice were epiilluminated with a mercury lamp and observed with a Leitz Ultrapak objective (22X) and dipping cone. The internal diameters were measured with an ocular micrometer. The Instrumentation for Physiology and Medicine (IPM) velocimeter and cross correlator were used to measure red blood cell (RBC) velocity at the centerline of 17 different microvascular branch points. The velocity in the feeding arteriole and each branch or in the tributaries and draining venule were used, together with the respective diameters, to calculate flow in each vessel. Findings in the arterioles and venules were combined, because the results were the same in either set of vessels.

Results: Flow in the main vessel (nl/sec) = 0.97 (sum of flow in branches or tributaries) +2. The correlation coefficient was 0.95. The relationship was not significantly different from an ideal slope of unity. However, in individual bifurcations the sum of flows in branches or tributaries deviated by as much as 40% from predicted values.

Conclusions: On the average, conservation of flow was present. The deviations from conservation at individual bifurcations were similar to those reported by others who utilized transilluminated beds. Thus, when conservation of flow is the validating criterion, the two‐slit technique used with epiillumination is not less valid than when used with transillumination.
Transvascular and Interstitial Migration of Neutrophils in Rat Mesentery
Authors: Ohashi K. L. , Tung D. K.‐L. , Wilson J. , Zweifach B. W. , Schmid‐Schönbein G. W.
Published: April 2008

Objective: The consequential implications of the leukocyte‐endothelial cell adhesion reaction, as well as the subsequent migratory activity of the leukocytes within the interstitium proper, are currently known only in general phenomenological terms. Our objective was to carry out a detailed quantitative analysis of transendothelial and interstitial migration.

Method: We incorporated several new features, such as the video recording of time‐lapse photography in conjunction with the time history of individual leukocytes under the influence of representative stimulators and inhibitors. The mesentery was suffused with the chemical activator N‐formyl‐met‐leu‐phe (fMLP, 5 ± 10−8 M) and histamine (10−6 M) for periods up to 3 h. This leads to an attachment of neutrophils preferentially to the walls of small postcapillary venules followed by migration into the adjacent interstitium.

Results: The time interval between the initial neutrophil adhesion to the luminal side of the venules and their first appearance on the abluminal side of the venule wall was about 25 min. The time interval for the actual physical migration across the endothelium was only about 1‐2 min. There was an initial increase in the number of neutrophils migrating across the wall per unit time after the application of fMLP. However, this effect then gradually decreased over the course of 1 h. In the extravascular tissue, the neutrophils appeared to migrate along random pathways with an average trajectory away from the venular wall. When histamine (1 μM) was applied topically in conjunction with fMLP, the overall migratory flux across the venular wall increased, although the cells migrated comparatively short distances into the interstitium. After pretreatment with phalloidin (25 μg/kg), an actin cross‐linking agent, neutrophil adhesion and migration in response to fMLP stimulation was reduced. The mast cell stimulator 48/80 (25 mg/ml) resulted in rapid degranulation, which was accompanied by an insignificant increase in neutrophil diapedesis. After fMLP stimulation there was reduced neutrophil emigration in the presence of mast cell inhibitors, such as lodoxamide (1 μg/kg) and ketotifin (1 μg/kg).

Conclusions: Our results demonstrate that both the endothelial cells and interstitial mast cells are involved in the rate of transvascular migration of leukocytes across postcapillary venules and into the interstitium.
Regulation of the Gene‐Encoding Angiotensin II Receptor in Vascular Tissue
Authors: Wang Donna H. , Du Yong , Yao Aqing
Published: April 2008

Specific angiotensin (Ang)‐dependent mechanisms significantly contribute to vascular development and function, and to the pathophysiology of hypertension. The effects of Ang II are mediated by binding to specific receptors. The focus of most studies has been changes in vascular function and structure in response to Ang II. Relatively little is known regarding the molecular basis of changes in the vascular Ang II receptor. We have recently found that, without altering blood pressure, Ang II infusion at a dose of 25 ng · kg · min−1 decreases expression of the gene‐encoding Ang II type 1 (AT1) receptor in both the aorta and resistant arteries. This suggests that exogenous Ang II negatively regulates AT1 mRNA expression in these tissues. Furthermore, hypertension induced by reduced renal mass plus high salt intake upregulates AT1 mRNA expression in the hypertrophied aorta and heart. In this model, the reduction of Ang II formation by captopril without decreasing blood pressure prevents the increase in AT1 mRNA in the aorta but not in the heart. This suggests that the regulation of AT1 gene expression in the heart may be pressure‐dependent while there is an Ang II‐dependent mechanism operant in the aorta. The precise tissue‐specific control mechanisms for AT1 gene expression remain to be defined.
A New Method for Blood Velocimetry in the Microcirculation
Authors: Hitt Darren L. , Lowe Mary L. , Tincher Juvena R. , Watters J. Michael
Published: April 2008

We describe a simple new method for computing two‐dimensional velocity vector fields of blood flows in microvascular networks. This method, known as optical flow, requires a time sequence of two or more images obtained by a process such as conventional videomicroscopy. There is no need to distinguish individual cells provided clear variations in the light intensity levels are present in the images. The result of the computation reveals the velocity distribution in the microvascular network and the geometry of the blood vessels. Although various implementations of the optical flow technique exist, we have found that the spatial correlation algorithm of Anandan performs best for microcirculatory flows. This report is an introduction to the application of optical flow to the microcirculation and provides instructions on how to obtain and run the codes.
Control Mechanisms of Retinal Vein Pressure: Evaluation in the Cat Using an In Situ Infusion Micropipette
Authors: Attariwala R. , Glucksberg M. R.
Published: April 2008

Objective: Previous work in our laboratory has shown that retinal vein pressure is significantly greater than intraocular pressure in the cat. Our purpose here is to evaluate the potential of an active mechanism being responsible for the control of vein pressure in the cat retina.

Methods: A double‐lumen, concentric barrel micropipette assembly designed for operation within the eye of a spontaneously breathing anesthetized cat was developed. The micropipette, initially filled with hypertonic saline for use with a servonull pressure measuring system, was used to determine intravascular pressure. With the tip of the micropipette still situated in the lumen of the vessel the solution in the micropipette was exchanged for papaverine, a potent smooth muscle dilator. Following vasodilation in the distal portion of a major retinal vein, the papaverine was exchanged for hypertonic saline and intravascular pressures were measured in the dilated vessel.

Results: Microinjection of papaverine caused visible dilation of the major retinal vein downstream from the site of microinjection. This indicates a relaxation of the smooth muscle yet papaverine caused no change in measured retinal vein pressure.

Conclusions: Vein pressure in the cat retina is maintained above intraocular pressure by mechanisms other than active control. A passive high‐resistance segment resides somewhere within the optic nerve possibly within the lamina cribosa or prelaminar region.
Theoretical Studies of Steady‐State Transcapillary Exchange in Countercurrent Systems
Authors: Wang W. , Parker K. H. , Michel C. C.
Published: April 2008

Objective: As a first step in modeling microvascular exchange in the renal medulla, we developed mathematical models to explore the effects of blood flow, permeability, and anatomical arrangement of microvessels on the steady‐state distribution of solute in the blood and the interstitial fluid (ISF).

Methods: Single capillaries and countercurrent capillary loops were used to model microvessels that were surrounded by a secretory epithelium over either the whole or part of the capillary length. Solute concentration in the vessels and the ISF were derived analytically. We also derived approximate solutions that ignored axial diffusion of solute.

Results: The full and approximate solutions were in good agreement with data based on measurements in the renal medulla. Model results revealed that concentration in the ISF falls rapidly with distance beyond the region of solute secretion and equilibrates with the concentration in capillaries, even with countercurrent exchange between the two limbs of the capillary loop. The ratio of the product of the permeability and area to the flow of the afferent limb, γ1, is an important parameter. When γ1 > 4, countercurrent exchange in a capillary loop facilitates a greater ISF concentration gradient than with a single capillary. Changes in flow also have a greater effect on this gradient.

Conclusion: The model of countercurrent exchange presented here not only demonstrates the sensitivity of interstitial concentration gradients of solute to flow through capillary loops but also reveals the importance of the absolute value of γ1 in determining the magnitude and direction of these gradients.
Induction of Cyclooxygenase‐2 Following Anoxic Stress in Piglet Cerebral Arteries
Authors: Busija David W. , Thore Clara , Beasley Tracy , Bari Ferenc
Published: April 2008

Objective: Ischemic stress causes damage to cerebrovascular endothelium and alters arteriolar responses to prostanoid‐dependent stimuli. However, effects of ischemic stress on cyclooxygenase (COX) levels in endothelium are unclear. We examined the effect of ischemia and reperfusion and asphyxia and reventilation on production of COX isoforms in cerebral vascular endothelium.

Methods: Neonatal pigs were exposed to global ischemia (n= 4) or asphyxia (n= 3) for 5–10 min. Following 2–6 h of recovery, the animals were killed, and the cerebral arteries and arterioles were removed. Cerebral arteries and arterioles were also removed from untreated control animals (n= 1) and from time control animals (n= 3). Cerebral vessels were fixed in 4% formalin and paraffin embedded, and constitutive and inducible COX (COX‐1 and COX‐2, respectively) levels were assessed using indirect immunofluorescence.

Results: Hemotoxylin and eosin staining indicated that anoxic stress leads to enlargement of endothelial cells. Immunofluorescence for COX‐1 in endothelium was minimal in cerebral arteries and arterioles from control animals and did not show an increase in animals exposed to anoxic stress. Similarly, cerebral vessels from control animals showed little immunostaining for COX‐2. In contrast, immunofluorescence for COX‐2 was greatly increased in cerebral arteries and arterioles from animals exposed to asphyxia or ischemia.

Conclusions: We conclude that anoxic stress increases COX‐2 but not COX‐1 levels in cerebral endothelium.
Oxidative Stress During Platelet‐Activating Factor‐Induced Microvascular Dysfunction
Authors: Kurose Iwao , Argenbright Lawrence W. , Wolf Robert , Granger D. Neil
Published: April 2008

Objective: To assess the potential contribution of hydrogen peroxide (H2O2) to the leukocyte‐endothelial cell adhesion and increased microvascular permeability (to fluorescein isothiocyanate [FITC]‐albumin) observed in rat mesenteric venules exposed to platelet‐activating factor (PAF).

Methods: The production of oxidants derived from H2O2 in mesenteric tissue was monitored using the H2O2‐sensitive fluorochrome, dihydrorhodamine 123 (DHR). PAF elicited a rapid increase in both the rate of albumin extravasation and oxidation of DHR, which was followed by an increased adherence and emigration of leukocytes in postcapillary venules.

Results: The PAF‐induced oxidation of DHR, leukocyte‐endothelial cell interactions, and albumin leakage were attenuated by treatment with either catalase or dimethylthiourea. Treatment with monoclonal antibody directed against either CD11b/CD18 on leukocytes or ICAM‐1 on endothelial cells attenuated the PAF‐induced oxidative stress, albumin leakage, and leukocyte‐endothelial cell adhesion.

Conclusions: These findings indicate that most of the oxidants generated in mesenteric tissue exposed to PAF results from the accumulation of activated leukocytes.