bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Apoptosis Coincides with Onset of Involution in Infantile Hemangioma
Authors: RAZON MARIA J. , KRÄLING BIRGIT M. , MULLIKEN JOHN B. , BISCHOFF JOYCE 
Published: January 2010

ABSTRACTObjective: Hemangioma is an endothelial cell tumor that grows rapidly during infancy and regresses slowly during childhood. However, little is known about the natural history of this common tumor. To gain insight into the cellular mechanisms that underlie the switch from uncontrolled growth to involution of endothelium, we investigated the extent of cellular apoptosis versus proliferation in hemangioma specimens that spanned the natural life cycle of the tumor.Methods: We analyzed apoptosis and cellular proliferation in frozen sections from 16 hemangioma specimens using the TUNEL assay to detect apoptotic cells and the Ki67 antigen to detect dividing cells.Results: Apoptosis was low in proliferative phase hemangiomas but increased fivefold in involutive phase specimens obtained from children one to four years of age. Immunofluorescence double‐labeling experiments showed that at least one third of the apoptotic cells were endothelial. As expected, cellular proliferation was high in specimens up to 2 years of age but decreased significantly thereafter. Apoptosis was consistently low in nine normal skin tissues (newborn to 4 years of age) obtained from discarded pathology specimens.Conclusions: These results suggest that increased apoptosis during the second year of life can offset cellular proliferation and may be involved in initiating regression of hemangioma.
Expression of Zonula Occludens and Adherens Junctional Proteins in Human Venous and Arterial Endothelian Cells: Role of Occludin in Endothelial Solute Barriers
Authors: KEVIL CHRISTOPHER G. , OKAYAMA NAOTSUKA , TROCHA STEVEN D. , KALOGERIS THEODORE J. , COE LAURA L. , SPECIAN ROBERT D. , DAVIS CHRISTOPHER P. , ALEXANDER J. STEVEN 
Published: January 2010

ABSTRACTObjective: The purpose of this study was to correlate the expression of occludin and VE‐cadherin with the solute barrier properties of arterial and venous endothelial monolayers.Methods: Immunofluorescent confocal and traditional microscopy were used to determine junctional protein localization in endothelium in vivo and in vitro respectively, and western and northern analysis used to determine protein and gene expression levels. Permeability of endothelial monolayers was examined under normal, low calcium, and cytochalasin‐D treatment conditions. Antisense oligonucleotide experiments for occludin were performed to determine the contribution of occluding to solute barrier.Results: Occludin protein in endothelial monolayers in more concentrated in arterial junctions than in venous junctions both in vivo and in vitro. Arterial endothelial cells express 18‐fold more occluding protein and nine times more occluding mRNA compared to venous endothelial cells. In vivo, both endothelial cells demonstrate VE‐cadherin staining; in vitro, only venous endothelial cells express VE‐cadherin protein and mRNA. Occludin antisense experiments suggest that both arterial and venous barrier properties are due to these different amounts of occluding expression. Venous barrier was remarkably sensitive to low extracellular calcium, while arterial barrier was more sensitive to cytochalasin‐D.Conclusions: These findings suggest strongly that arterial and venous endothelial barrier reflects the level of expression of different adhesion molecules and that modulation of these proteins, especially occluding, may regulate the level of endothelial solute barrier.
Superoxide Dismutase Restores Impaired Histamine‐Induced Increase in Venular Macromolecular Efflux During Diabetes Mellitus
Authors: MAYHAN WILLIAM G. , SHARPE GLENDA M. 
Published: January 2010

ABSTRACTThe goal of this study was to determine the role of oxygen radicals in impaired histamine‐induced increases in venular macromolecular efflux from the hamster cheek pouch. We used intravital fluorescent microscopy and fluorescein isothio‐cynate dextran (FITC‐dextran; MW = 70 K) to examine macromolecular extravasation from post‐capillary venules in nondiabetic and diabetic (2–4 weeks after injection of streptozoticin) hamsters in response to histamine. Increases in extravasation of macromolecules were quantitated by counting venular leaky sites and by calculating clearance (ml/s × 10−6) of FITC‐dextran‐70 K. In non‐diabetic hamsters, superfusion with histamine (1.0 and 5.0 µM) increased venular leaky sites from 0 ± 0 to 17 ± 6 and 35 ± 6 per 0.11 cm2, respectively. In addition, clearance of FITC‐dextran‐70 K increased during superfusion with histamine. In contrast, superfusion with histamine did not increase the formation of venular leaky sites (0 ± 0) or clearance of FITC‐dextran‐70 K in diabetic hamsters. Next, we examined whether alterations in histamine‐induced increases in macromolecular efflux in diabetic hamsters may be related to the production of oxygen radicals. We examined whether exogenous application of superoxide dismutase (150 U/ml) could restore impaired histamine‐induced increases in macromolecular extravasation in diabetic hamsters. Application of superoxide dismutase did not alter histamine‐induced increases in venular leaky sites or clearance of FITC‐dextran‐70 K in nondiabetic hamsters. However, application of superoxide dismutase restored histamine‐induced increases in leaky site formation and clearance of FITC‐dextran‐70 K in diabetic hamsters towards that observed in nondiabetic hamsters. These findings suggest that oxygen radical formation appears to contribute to impaired macromolecular efflux in response to histamine during short‐term diabetes mellitus.
A β‐Actin Isotype Is Present in Rat Cardiac Endothelial Cells But Not in Cardiac Myocytes
Authors: GLYN MATTHEW C.P. , WARD BARBARA J. 
Published: January 2010

ABSTRACTObjective: Active constriction in cardiac capillary endothelial cells (CCECs) is controversial. It is thought by many researchers that CCECs are not actively involved in constriction; others believe that these cells do contribute some of the force required for capillary constriction. Because actin is a major component of most contractile mechanisms responsible for changing cell shape, we compared two probes as potential monitors of actin distribution in CCECs in situ.Methods: We used SDS‐PAGE, Western blotting, electron microscopy, conventional epifluorescence and confocal microscopy to evaluate an antibody against non‐muscle β‐actin and fluorescently labeled phalloidin to detect actin in CCECs.Results: Fluorescently labeled phalloidin detected actin in cardiac muscle and faintly in CCECs. The antibody probe detected non‐muscle β‐actin in CCECs. However, this actin isotype did not occur in cardiac myocytes. In endothelial cells non‐muscle β‐actin was concentrated at the cell periphery, and arranged as bundles of fibers, not as typical stress fibers.Conclusions: Phalloidin is not suitable as a probe to monitor actin distribution in CCEC's in situ. The antibody is a potentially useful tool in monitoring the actin cytoskeleton and determining the capacity of CCECs for active vasoconstriction in vivo. Non‐muscle β‐actin in CCECs is arranged in filament bundles which are not typical stress fibers.
Endothelin Mediates a Component of the Enhanced Myogenic Responsiveness Of Arterioles From Hypertensive Rats
Authors: FALCONE JEFF C. , MEININGER GERALD A. 
Published: January 2010

ABSTRACTObjective: To determine if the enhanced pressure‐induced constriction of arterioles isolated from hypertensive rats is mediated by the endothelium.Methods: We utilized isolated, cannulated first‐order arterioles (80 to 110 µm, i.d.) from the rat cremaster muscle of spontaneously hypertensive (SHR) and normotensive (WKY) rats. Arteriolar diameter was measured in response to changes in intraluminal pressures as well as various pharmacological agents in the presence and absence of an intact endothelial cell lining.Results: All arterioles developed intrinsic tone (approximately 74% of passive). Pressure‐diameter relationships over a pressure range of 30 to 170 cm H2O demonstrated that the myogenic response of arterioles derived from both WKY and SHR was not dependent upon an intact endothelium. However, at higher pressures (>170 cm H2O) the ability of the denuded arteriole from the SHR to maintain a constricted diameter was completely abolished. Treatment of arterioles from the SHR having intact endothelium with diclofenac (10−5 M; 30 min) to inhibit the effect of cyclooxygenase had no effect on the high pressure constriction. In contrast, application of BQ‐123 (10−7 M; 30 min), an ET‐A receptor blocker used to inhibit vascular smooth muscle responses to endothelin, completely abolished the arteriolar constriction at higher pressures.Conclusions: Therefore, in the hypertensive, arteriolar vasomotor responses to changes in intraluminal pressure is due to at least two mechanisms; one that is intrinsic to vascular smooth muscle (i.e., myogenic) and a second that involves an endothelial cell release of endothelin.
The Pancreas as a Source of Cardiovascular Cell Activating Factors
Authors: KISTLER ERIK B. , HUGLI TONY E. , SCHMID‐SCHÖNBEIN GEERT W. 
Published: January 2010

ABSTRACTObjective: Physiological shock leads to elevated levels of plasma factors that activate circulating leukocytes and endothelial cells, thereby compromising microvascular functions. The nature and source of these plasma‐derived activators are unknown. To examine the possible origin of these factors, we homogenized rat internal organs and measured their activity on cardiovascular cells in vivo and in vitro.Methods: Fresh tissue samples from small intestine, spleen, heart, liver, kidney, adrenals, and pancreas were homogenized. Their ability to induce leukocyte pseudopod formation and nitroblue tetrazolium (NBT) reduction was tested and their impact in vivo on blood pressure, survival, and microvascular cell injury was examined.Results: A dramatic increase (p < 0.001) in leukocyte activation compared to controls was observed with pancreas homogenate but not with homogenates from the other organs. Leukocyte activation was induced by homogenates of other tissues only after prior incubation with substimulatory concentrations of pancreatic homogenate. Pancreatic serine proteases, trypsin and chymotrypsin, which did not stimulate leukocytes, also generated activity from other tissues. Leukocyte pseudopod formation could be significantly inhibited by adding the serine protease inhibitor 6‐amidino‐2‐naphthyl p‐guanidinobenzoate dimethanesulfonate (ANGD) during tissue homogenization (p < 0.001). Injection of pancreatic homogenate into rats led to increased plasma hydrogen peroxide levels and an instantaneous drop in mean arterial pressure that was often lethal. These responses were prevented by prior infusion of ANGD (p < 0.001). Intravital microscopy of the rat mesentery confirmed that superfusion of filtered pancreatic homogenate leads to significant increases in cell death (p < 0.05), as detected by propidium iodide, and hydrogen peroxide formation (p < 0.05), as determined by dichlorofluorescein diacetate (DCFH) fluorescence.Conclusion: These results suggest that pancreatic enzymes attack tissue and generate cellular activators that are associated with organ dysfunction in shock.
Requirement of Arteriovenular Pairing for Increased Capillary Filtration During Acute Inflammation
Authors: BARNIDGE JASON , HARRIS NORMAN R. 
Published: January 2010

ABSTRACTObjective: The purpose of this study was to determine whether the leukocyte chemoattractant N‐formyl methionyl‐leucyl‐phenylalanine (FMLP) increases capillary fluid filtration rate (Jv/S), and if so, to determine whether the mechanism involves arteriovenular communication.Methods: Intravital microscopy was used in the rat mesentery to measure capillary Jv/S by a micro‐occlusion technique. FMLP was locally superfused through a micropipette near vessels in three different arrangements: 1) near a venule in close pairing with the arteriole feeding the monitored capillary, 2) near an unpaired arteriole feeding the capillary, or 3) near an unpaired venule draining the capillary. In separate experiments, arteriolar hydrostatic pressure (downstream of arteriovenular pairing sites exposed to FMLP) was measured with a micropressure system.Results: FMLP increased capillary Jv/S when applied to arteriovenular pairing sites, but not when applied to unpaired arterioles or venules. Micropressure measurements in paired arterioles remained essentially constant during FMLP exposure, suggesting that the increase in Jv/S is primarily due to increased capillary permeability.Conclusions: With FMLP applied locally to stimulate leukocytes, arteriovenular pairing is required to observe an increase in capillary filtration rate.
Contribution of Extrinsic Factors and Intrinsic Vascular Alterations to Reduced Arteriolar Reactivity with High‐Salt Diet and Hypertension
Authors: FRISBEE JEFFERSON C. , SYLVESTER FRANCIS A. , LOMBARD JULIAN H. 
Published: January 2010

ABSTRACTObjective: To determine whether the impaired relaxation of skeletal muscle arterioles of rats on high‐salt diet or with reduced renal mass hypertension (RRM‐HT) represents intrinsic alterations to microvessels alone, or whether extravascular influences also contribute to reduced dilator responses.Methods: Normotensive (NT) Sprague‐Dawley rats were fed low‐salt (LS) or high‐salt (HS) diets, and RRM‐HT rats were fed HS diet for 4–6 weeks. In situ and isolated cremaster muscle first‐order arterioles (1A) were examined using television microscopy, and a video micrometer was used to measure diameter changes in response to acetylcholine (ACH), cholera toxin (CT), and sodium nitroprusside (SNP).Results: Compared to normotensive low‐salt (NT‐LS) rats, responses of 1A to the agonists were reduced in normotensive high‐salt (NT‐HS) and RRM‐HT rats. Arteriolar reactivity to the agonists in NT‐LS rats and in NT‐HS rats was not different between in situ and in vitro environments. However, in RRM‐HT rats, the reactivity of 1A to each agonist was greater in isolated arterioles than in in situ arterioles.Conclusions: These results suggest that the impaired response of skeletal muscle arterioles to vasodilator stimuli in normotensive rats on high‐salt diet primarily reflects alterations to microvessels alone, while reduced dilator responses in RRM‐HT rats represent a combination of extravascular influences and intrinsic alterations to arterioles themselves.
Roles of Endothelial Cell Migration and Apoptosis in Vascular Remodeling during Development of the Central Nervous System
Authors: HUGHES SUZANNE , CHAN‐LING TAILOI 
Published: January 2010

ABSTRACTObjective: To examine the roles of apoptosis, macrophages, and endothelial cell migration in vascular remodeling during development of the central nervous system.Methods: The terminal deoxynucleotide transferase‐mediated dUTP nick end labeling (TUNEL) technique was combined with Griffonia simplicifolia isolectin B4 histochemistry to detect apoptotic endothelial cells in retinal whole‐mount preparations derived from rats at various stages of postnatal development as well as from rat pups exposed to hyperoxia. Macrophages were detected by immunohistochemistry with the monoclonal antibody ED1, and proliferating endothelial cells were identified by incorporation of bromodeoxyuridine.Results: Only small numbers of TUNEL‐positive endothelial cells were detected during normal development of the retinal vasculature, with the apoptotic cell density in the inner plexus peaking during the first postnatal week and decreasing markedly during the second week, at a time when vessel retraction was widespread. Neither apoptotic endothelial cells nor macrophages were apparent at sites of initiation of vessel retraction. TUNEL‐positive endothelial cells were observed in vessels destined to remain. Hyperoxia induced excessive vessel withdrawal, resulting in the generation of isolated vascular segments containing apoptotic endothelial cells. A topographical analysis showed low numbers of proliferating endothelial cells at sites of angiogenesis whereas vascular proliferation was increased in the adjacent inner plexus.Conclusions: Endothelial cell apoptosis and macrophages do not initiate vessel retraction, but rather contribute to the removal of redundant cells throughout the vasculature. We suggest that vessel retraction is mediated by endothelial cell migration and that endothelial cells derived from retracting vascular segments are redeployed in the formation of new vessels. Only when retraction results in compromised circulation and redeployment is not possible, does endothelial cell apoptosis occur.
Interaction of Endothelin‐1 and Nitric Oxide in Endothelial Barrier Failure in the Cat Hindlimb
Authors: PORTER LINDA P. , McNAMEE JAMES E. , WOLF MATTHEW B. 
Published: January 2010

ABSTRACTObjective: To determine the interactions of endothelin‐1 (ET‐1) and nitric oxide (NO) in the regulation of endothelial barrier function in skeletal muscle.Methods: The protein sieving coefficient (1 − σf) was measured as an index of microvascular permeability in the isolated, perfused cat hindlimb preparation. The measurement was made to determine 1) the effects of ET‐1 and NO on basal permeability by blocking the ETAreceptor with BQ123 and NO production with the NO‐synthase inhibitorsl‐NAME orl‐NMMA; 2) if elevated NO (SNAP) affects permeability; and 3) the interaction of ET‐1 and NO by ascertaining if NO‐synthase inhibition or elevated NO can block the ET‐1‐induced permeability increases. Additionally, vascular resistance was determined under these conditions to see if increased microvascular pressures or increased shear stress might play a role in the permeability changes.Results: Blocking either the ETAreceptor or basal NO production did not affect basal permeability. Likewise, raising NO levels did not affect this permeability. Blocking the ETAreceptor blocked the ability of ET‐1 to cause a profound barrier failure. Increased NO also could block this ET‐1‐induced effect. Blocking the ETAreceptor or elevating NO blocked the 2.5‐fold increase in vascular resistance induced by ET‐1.Conclusions: Since the ETAreceptor does not reside on skeletal muscle endothelium, it is not likely that ET‐1 acts directly on the endothelium to produce its effects. It could act through 1) increases in shear stress secondary to an ET‐1‐induced vasoconstriction; 2) ET‐1‐induced increases in microvascular pressure sufficient to cause an inflammatory reaction; or 3) stimulation of other cell types, such as leukocytes, to release inflammatory mediators that could damage the endothelium.
Transport of Viral‐Size Particulate Matter after Intravenous versus Intralymphatic Entry
Authors: FOKIN ALEXANDER A. , ROBICSEK FRANCIS , MASTERS THOMAS N. 
Published: January 2010

ABSTRACTObjective: Investigation of the transport of viral‐size particles after intravenous versus intralymphatic injection and the functional validity of lymphatico‐venous communications.Methods: In the canine model, [99mTc] sulfur colloid particles (100–200 nm) were injected into either the principal vein or into the main lymphatic channel exposed at the paw. Samples of blood and lymph were collected at the groin from the cannulated femoral vein and from a major lymphatic vessel. Parameters including particle arrival time, concentration, flux, and accumulation were determined for a 45‐minute period using gamma counting.Results: After intralymphatic injection, particles arrived in the venous blood in an average of 4 seconds. The mean arrival time of particles in the lymph after intravenous injection was 25.4 ± 6.44 minutes. Intralymphatic injection increased lymph flow and enhanced particle transport. Concentration values in the venous blood after intralymphatic injection and in lymph after intravenous injection were comparable. Flux values depended primarily on flow conditions. Particle accumulation in the lymph after intravenous injection was delayed, but continued to increase throughout the experiment.Conclusions: There are functional lymphatico‐venous communications at the very peripheral level under physiological conditions, which allow rapid transport of viral‐size particulate matter between the two pathways and may contribute to the spread of viral infection.
Therapeutic Management of Chronic Venous Insufficiency: Microcirculation as a Target
Authors: BERGAN JOHN J. , SCHMID‐SCHÖNBEIN GEERT W. 
Published: January 2010

ABSTRACTChronic venous insufficiency, in its most severe manifestations as well as in its mild form, is linked to venous valve failure, weakness of the venous wall, and leukocyte‐endothelial interactions all of which lead to cutaneous and subcutaneous tissue changes. These in turn are related to venous hypertension‐induced leukocyte activation, which may provide a target for pharmacotherapeutic intervention. Currently, surgical attack is focused on correction of the sources of venous hypertension, but it is felt that this provides a crude method that hopefully will be replaced by more precise pharmacological interventions.
Biological Properties of Flavonoids Pertaining to Inflammation
Authors: MANTHEY JOHN A. 
Published: January 2010

ABSTRACTChronic venous insufficiency (CVI) is accompanied by a marked inflammatory response that is thought to contribute to the development and progression of the disorder. While compression therapy has long been considered the standard treatment for CVI, recent studies suggest that treatment with flavonoids may also be beneficial. The purpose of this review is to summarize how plant flavonoids attenuate inflammation and the immune response through their inhibition of important regulatory enzymes. Certain flavonoids are potent inhibitors of the production of prostaglandins, a group of powerful proinflammatory signaling molecules. Studies have shown that this effect is due to flavonoid inhibition of key enzymes involved in prostaglandin biosynthesis (i.e., lipoxygenase, phospholipase, and cyclooxygenase). Flavonoids also inhibit phosphodiesterases involved in cell activation. Much of this effect is upon the biosynthesis of protein cytokines that mediate adhesion of circulating leukocytes to sites of injury. The protein kinases are another class of regulatory enzymes affected by flavonoids. The inhibition of kinases is due to the competitive binding of flavonoids with ATP at catalytic sites on the enzymes. These modes of inhibition provide the mechanisms by which flavonoids inhibit the inflammation response and suggest that this class of molecules may be effective in the treatment of CVI.
Micronized Purified Flavonoid Fraction and the Treatment of Chronic Venous Insufficiency: Microcirculatory Mechanisms
Authors: SMITH PHILIP D. COLERIDGE 
Published: January 2010

ABSTRACTThe standard treatments for venous diseases of the lower limb include compression bandaging and stockings as well as surgical removal of varicose veins. There is a number of conditions in which these conventional treatments are ineffective, particularly in the management of leg ulceration. Drug treatments for healing venous leg ulcers have yet to be developed to the stage of good clinical efficacy, but may assist in the management of patients. Flavonoid drugs have been widely used in the management of the symptoms of venous disease for many years and have recently been studied in some detail to assess their effects on the microcirculation. Work in animal models of ischemia/reperfusion (I/R) show that micronized purified flavonoid fraction (MPFF) modulates leukocyte adhesion and prevents endothelial damage. Similar biochemical effects have been observed in patients with venous disease and may explain the efficacy of this drug in the management of edema and other symptoms of venous disease. There is some evidence that MPFF promotes venous leg ulcer healing.