Home About us Contact
|
Home About us Contact | ||
|
|
||
Venules
Kinds of Venules Selected AbstractsVascular response to laser photothermolysis as a function of pulse duration, vessel type, and diameter: Implications for port wine stain laser therapyLASERS IN SURGERY AND MEDICINE, Issue 2 2002Sol Kimel PhD Abstract Background and Objective Treatment of port wine stains (PWS) by photothermolysis can be improved by optimizing laser parameters on an individual patient basis. We have studied the critical role of pulse duration (tp) on the treatment efficacy. Study Design/Materials and Methods The V-beam laser (Candela) allowed changing tp over user-specified discrete values between 1.5 and 40 milliseconds by delivering a series of 100 microsecond spikes. For the 1.5 and 3 millisecond pulses, three spikes were observed at intervals tp/2 and for tp,,,6 milliseconds, four spikes separated by tp/3. The ScleroPlus laser (Candela) has a smooth output over its fixed 1.5 milliseconds duration. Blood vessels in the chick chorioallantoic membrane (CAM) were irradiated at fixed wavelength (595 nm), spot size (7 mm), radiant exposure (15 Jcm,2), and at variable tp. The CAM contains an extensive microvascular network ranging from capillaries with diameter D,<,30 ,m to blood vessels of D,,,120 ,m. The CAM assay allows real-time video documentation, and observation of blood flow in pre-capillary arterioles (A) and post-capillary venules (V). Vessel injury was graded from recorded videotapes. Mathematical modeling was developed to interpret results of vessel injury when varying tp and D. A modified thermal relaxation time was introduced to calculate vessel wall temperature following laser exposure. Results Arterioles. For increasing tp, overall damage was found to decrease. For fixed tp, damage decreased with vessel size. Venules. For all D, damage was smaller than for corresponding arterioles. There was no dependence of damage on tp. For given tp, no variation of damage with D was observed. Photothermolysis due to spiked (V-beam) vs. smooth (Scleroplus) delivery of laser energy at fixed tp (1.5 milliseconds), showed similar vessel injuries for al values of D (P>0.05). Conclusions The difference between initial arteriole and venule damage could be explained by the threefold higher absorption coefficient at 595 nm in (oxygen-poor!) arterioles. In human patients, PWS consist of ectatic venules (characterized by higher absorption), so that these considerations favor the use of 595-nm irradiation for laser photothermolysis. For optimal treatment of PWS it is proposed that tp be between 0.1 and 1.5 milliseconds. This is based on a modified relaxation time ,d,, defined as the time required for heat conduction into the full thickness of the vessel wall, which is assumed to have a thickness ,D ,,0.1D. The corresponding ,d, will be a factor of about six smaller than given in the literature. For vessels with D between 30 and 300 ,m, ,d, ranges from 0.1 to 1.5 milliseconds. Lasers Surg. Med. 30:160,169, 2002. © 2002 Wiley-Liss, Inc. [source] Losartan and Ozagrel Reverse Retinal Arteriolar Constriction in Non-Obese Diabetic MiceMICROCIRCULATION, Issue 5 2008Seungjun Lee ABSTRACT Objective: Reductions in retinal blood flow are observed early in diabetes. Venules may influence arteriolar constriction and flow; therefore, we hypothesized that diabetes would induce the constriction of arterioles that are in close proximity to venules, with the constriction mediated by thromboxane and angiotensin II. Methods: Using nonobese diabetic (NOD) mice, retinal measurements were performed three weeks following the age at which glucose levels exceeded 200 mg/dL, with accompanying experiments on age-matched normoglycemic NOD mice. The measurements included retinal arteriolar diameters and red blood cell velocities and were repeated following an injection of the thromboxane synthase inhibitor, ozagrel. Mice were subdivided into equal groups and given drinking water with or without the angiotensin II receptor antagonist, losartan. Results: Retinal arterioles were constricted in hyperglycemic mice, with a significant reduction in flow. However, not all arterioles were equally affected; the vasoconstriction was limited to arterioles that were in closer proximity to venules. The arteriolar vasoconstriction (mean arteriolar diameters = 51 ± 1 vs. 61 ± 1 , m in controls; p < 0.01) was eliminated by both ozagrel (61 ± 2 , m) and losartan (63 ± 2 , m). Conclusions: Venule-dependent arteriolar vasoconstriction in NOD mice is mediated by thromboxane and/or angiotensin II. [source] Microvascular Thrombosis Models in Venules and Arterioles In VivoMICROCIRCULATION, Issue 3 2005ROLANDO E. RUMBAUT MD ABSTRACT Platelets are intimately involved in hemostasis and thrombosis. Under physiological conditions, circulating platelets do not interact with microvascular walls. However, in response to microvascular injury, platelet adhesion and subsequent thrombus formation may be observed in venules and arterioles in vivo. Numerous intravital video microscopy techniques have been described to induce and monitor the formation of microvascular thrombi. The mechanisms of microvascular injury vary widely among different models. Some models induce platelet activation with minimal effects on endothelium, others induce endothelial inflammation or injury, while other models lead to thrombus formation associated with endothelial denudation. The molecular mechanisms mediating platelet,vessel wall adhesive interactions differ among various models. In some instances, differences in responses between venules and arterioles are described that cannot be explained solely by hemodynamic factors. Several models for induction of microvascular thrombosis in vivo are outlined in this review, with a focus on the mechanisms of injury and thrombus formation, as well as on differences in responses between venules and arterioles. Recognizing these characteristics should help investigators select an appropriate model for studying microvascular thrombosis in vivo. [source] GlcNAc6ST-1-mediated decoration of MAdCAM-1 protein with L-selectin ligand carbohydrates directs disease activity of ulcerative colitisINFLAMMATORY BOWEL DISEASES, Issue 5 2009Motohiro Kobayashi MD Abstract Background: A diffuse lymphocyte infiltrate is 1 of the characteristic features of ulcerative colitis (UC). Such lymphocyte recruitment requires lymphocyte rolling mediated by L-selectin ligand carbohydrates (6-sulfo sialyl Lewis X-capped O -glycans) and/or mucosal addressin cell adhesion molecule 1 (MAdCAM-1) expressed on high endothelial venule (HEV)-like vessels. The present study was undertaken to elucidate the role of MAdCAM-1 posttranslationally modified ("decorated") with L-selectin ligand carbohydrates in UC pathogenesis and consequent clinical outcomes. Methods: Biopsy specimens composed of active and remission phases of UC as well as normal colonic mucosa were immunostained for CD34, MAdCAM-1, and MECA-79, and the immunostained sections were quantitatively analyzed. Reverse-transcriptase polymerase chain reaction (RT-PCR) was carried out to evaluate transcripts of MAdCAM-1 and N -acetylglucosamine-6- O -sulfotransferases (GlcNAc6STs). CHO and Lec2 cells transfected with CD34 and MAdCAM-1 together with enzymes involved in L-selectin ligand carbohydrate biosynthesis were analyzed by immunofluorescence, FACS, and Western blotting to characterize the biochemical properties of GlcNAc6STs. Results: The number of MAdCAM-1+ vessels was increased in UC, with no significant difference between active and remission phases. An increased ratio of MECA-79+ to MAdCAM-1+ vessels with preferential GlcNAc6ST-1 transcripts was observed in the active phase of UC compared to the remission phase. MAdCAM-1 protein was colocalized with L-selectin ligand carbohydrates at the luminal surface of HEV-like vessels in situ. GlcNAc6ST-1 preferentially utilizes MAdCAM-1 as a scaffold protein for GlcNAc-6- O -sulfation in L-selectin ligand carbohydrate biosynthesis. Conclusions: UC disease activity is not regulated by expression of MAdCAM-1 protein itself, but rather by GlcNAc6ST-1-mediated decoration of MAdCAM-1 protein with L-selectin ligand carbohydrates. (Inflamm Bowel Dis 2008) [source] P-selectin mediates leukocyte rolling in concanavalin-A-induced hepatitisLIVER INTERNATIONAL, Issue 5 2005Sandra March Abstract: Concanavalin- A (Con-A)-induced hepatitis is an experimental model of human autoimmune hepatitis characterized by leukocyte activation and infiltration of the liver. The aim of the present study was to evaluate the role of P-selectin on leukocyte,endothelial interactions within the hepatic microvasculature in response to Con-A. Methods: The study was performed in P-selectin-deficient mice and wild-type mice pretreated with anti-P-selectin blocking monoclonal antibody (mAb) or vehicle. After 2 h of Con-A (20 mg/kg i.v.) or PBS administration, leukocyte rolling and adhesion and the index of sinusoidal perfusion were evaluated using the intravital microscopy technique in the liver. Apoptosis was determined by flow cytometry analysis of caspase-3 activity assayed on freshly isolated hepatocytes. Results: Con-A induced a significant increase in leukocyte rolling, mainly located at the central venule (2.1±0.4 vs 0.6±0.2 cells/min in wild-type mice treated with vehicle) and less marked, but still significant, in portal venules. This was associated with a significant increase in leukocyte adhesion. In P-selectin-deficient mice treated with Con-A, leukocyte rolling in portal and central venules was markedly reduced. However, leukocyte adhesion was only partially attenuated. A few sinusoids were perfused in wild-type mice treated with Con-A (26%). The percentage of perfused sinusoids was significantly higher in P-selectin-deficient mice (45%; P<0.05 vs wild-type). Similar effects were noted after the simultaneous injection of Con-A and anti-P-selecting mAb in wild-type mice. After Con-A treatment, apoptosis was markedly reduced in isolated hepatocytes of P-selectin-deficent mice (37±7% vs 75±5% in wild type). Conclusion: The results of this intravital microscopy study clearly demonstrate that P-selectin is involved in the initial leukocyte rolling that leads to the development of Con-A-induced liver injury. [source] Morphological mechanisms for regulating blood flow through hepatic sinusoidsLIVER INTERNATIONAL, Issue 1 2000Robert S. McCuskey Abstract: This review summarizes what is known about the various morphological sites that regulate the distribution of blood flow to and from the sinusoids in the hepatic microvascular system. These sites potentially include the various segments of the afferent portal venules and hepatic arterioles, the sinusoids themselves, and central and hepatic venules. Given the paucity of smooth muscle in the walls of these vessels, various sinusoidal lining cells have been suggested to play a role in regulating the diameters of sinusoids and influencing the distribution and velocity of blood flow in these vessels. While sinusoidal endothelial cells have been demonstrated to be contractile and to exhibit sphincter function, attention has recently focused on the perisinusoidal stellate cell as the cell responsible for controlling the sinusoidal diameter. A very recent study, however, suggested that the principal site of vasoconstriction elicited by ET-1 was the pre-terminal portal venule. This raised the question of whether or not the diameters of sinusoids might decrease due to passive recoil when inflow is reduced or eliminated and intra-sinusoidal pressure falls. In more recent in vivo microscopic studies, clamping of the portal vein dramatically reduced sinusoidal blood flow as well as the diameters of sinusoids. The sinusoidal lumens rapidly returned to their initial diameters upon restoration of portal blood flow suggesting that sinusoidal blood pressure normally distends the sinusoidal wall which can recoil when the pressure drops. Stellate cells may be responsible for this reaction given the nature of their attachment to parenchymal cells by obliquely oriented microprojections from the lateral edges of their subendothelial processes. This suggests that care must be exercised when interpreting the mechanism for the reduction of sinusoidal diameters following drug administration without knowledge of changes occurring to the portal venous and hepatic inflow. [source] Inhibition of Leukocyte Adherence Enables Venular Control of Capillary Perfusion in Streptozotocin-Induced Diabetic RatsMICROCIRCULATION, Issue 8 2004KAVITHA NELLORE ABSTRACT Objective: Vasoactive molecules can diffuse from venules to dilate closely paired arterioles and enhance capillary perfusion. Venular control of capillary flow has been found to be dependent on nitric oxide (NO), which might be scavenged rapidly in diabetic microvasculature due to the presence of activated leukocytes. This study attempts to improve venular control of capillary flow using fucoidan, which inhibits venular leukocyte adhesion. Methods: Microvascular red blood cell velocity was measured in the mesentery of streptozotocin-induced diabetic rats, with and without fucoidan treatment, and in normal rats. Arteriolar pathways leading to branching capillaries were videotaped to measure the percent of the surrounding area occupied by a venule (% pairing). Microvascular wall NO was measured using fluorescent diaminofluorescein-2-diacetate in diabetic rats, with and without fucoidan treatment. Results: In normal rats, close pairing of venules to arterioles resulted in faster capillary flow. However, after 4,5 weeks of diabetes, the correlation between capillary velocity and % pairing was no longer significant. Capillary velocity and % pairing decreased , 50% in comparison to normal rats. Treatment of diabetic rats with fucoidan restored venular control of capillary flow and increased NO levels. Conclusion: Leukocyte-derived mediators that scavenge NO may lead to inadequate venular control of capillary flow in diabetes. [source] Anandamide mediates hyperdynamic circulation in cirrhotic rats via CB1 and VR1 receptorsBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2006L Moezi Background and purpose: Hyperdynamic circulation and mesenteric hyperaemia are found in cirrhosis. To delineate the role of endocannabinoids in these changes, we examined the cardiovascular effects of anandamide, AM251 (CB1 antagonist), AM630 (CB2 antagonist) and capsazepine (VR1 antagonist), in a rat model of cirrhosis. Experimental approach: Cirrhosis was induced by bile duct ligation. Controls underwent sham operation. Four weeks later, diameters of mesenteric arteriole and venule (intravital microscopy), arterial pressure, cardiac output, systemic vascular resistance and superior mesenteric artery (SMA) flow were measured after anandamide, AM251 (with or without anandamide), AM630 and capsazepine administration. CB1, CB2 and VR1 receptor expression in SMA was assessed by western blot and RT-PCR. Key results: Anandamide increased mesenteric vessel diameter and flow, and cardiac output in cirrhotic rats, but did not affect controls. Anandamide induced a triphasic arterial pressure response in controls, but this pattern differed markedly in cirrhotic rats. Pre-administration of AM251 blocked the effects of anandamide. AM251 (without anandamide) increased arterial pressure and systemic vascular resistance, constricted mesenteric arterioles, decreased SMA flow and changed cardiac output in a time-dependent fashion in cirrhotic rats. Capsazepine decreased cardiac output and mesenteric arteriolar diameter and flow, and increased systemic vascular resistance in cirrhotic rats, but lacked effect in controls. Expression of CB1 and VR1 receptor proteins were increased in cirrhotic rats. AM630 did not affect any cardiovascular parameter in either group. Conclusions and implications: These data suggest that endocannabinoids contribute to hyperdynamic circulation and mesenteric hyperaemia in cirrhosis, via CB1 - and VR1-mediated mechanisms. British Journal of Pharmacology (2006) 149, 898,908. doi:10.1038/sj.bjp.0706928 [source] Retinal oxygenation in diabetic retinopathyACTA OPHTHALMOLOGICA, Issue 2009SH HARDARSON Purpose Diabetic retinopathy (DR) is believed to cause retinal tissue hypoxia by damaging retinal capillaries. The purpose of this study was to examine the effect of diabetic retinopathy on oxygen saturation in retinal arterioles and venules. Methods The retinal oximeter (Oxymap ehf., Reykjavik, Iceland) is composed of a fundus camera, beam splitter and light filters. Specialized software calculates relative oxygen saturation from light absorption at two wavelengths of light (605nm and 586nm). One first or second degree temporal arteriole and venule were measured in one eye of 31 healthy individual and 28 patients with diabetic retinopathy. The diabetic patients had background DR (n=6), macular oedema (n=7), untreated preproliferative or proliferative DR (n=7) or stable proliferative DR after treatment (n=8). Statistical analyses were performed with an unpaired t-test, one-way ANOVA and Dunnett's post test. Results Retinal arteriolar saturation was 93±4% (n=31, mean±SD) in healthy subjects and 101±6% (n=28) in patients with DR (p<0.0001). Retinal venular saturation was 58±6% in healthy subjects and 67±8% in diabetic patients (p<0.0001). Arteriolar and venular saturation was higher in all subgroups of diabetic patients (see methods) than in healthy subjects. Conclusion Increased oxygen saturation in retinal vessels in diabetic retinopathy, also found by other researchers, is consistent with poor distribution of blood and oxygen to the retinal tissue rather than decreased total retinal blood flow. Poor distribution of oxygen may be caused by capillary dropouts and shunts as well as thickening of the capillary walls. Commercial interest [source] 5-Hydroxytryptamine-induced microvascular pressure transients in lungs of anaesthetized rabbitsACTA PHYSIOLOGICA, Issue 2 2001N. Sen We determined lung microvascular pressure transients induced by 5-hydroxytryptamine (5HT), by the micropuncture technique. We mechanically ventilated anaesthetized (halothane 0.8%), open-chested rabbits, in which we recorded pulmonary artery (PA), left atrial (LA) and carotid artery pressures and cardiac output. For 4-min periods of stopped ventilation, we constantly inflated the lung with airway pressure of 7 cmH2O, then micropunctured the lung to determine pressures in arterioles and venules of 20,25 ,m diameter. An intravenous bolus infusion of 5HT (100 ,g), increased total pulmonary vascular resistance by 59%. Prior to 5HT infusion, the arterial, microvascular and venous segments comprised 30, 50 and 19% of the total pulmonary vascular pressure drop, respectively. However 14 s after 5HT infusion, the PA-arteriole pressure difference (arterial pressure drop) increased 46%, while the venule-LA pressure difference (venous pressure drop) increased >100%. The arteriole,venule pressure difference (microvascular pressure drop) was abolished. The increase in the arterial pressure drop was maintained for 4.8 min, whereas the increased venous pressure drop reverted to baseline in <1 min. We conclude that in the rabbit lung in situ, a 5HT bolus causes sustained arterial constriction and a strong but transient venous constriction. [source] Early expression of endomucin on endothelium of the mouse embryo and on putative hematopoietic clusters in the dorsal aortaDEVELOPMENTAL DYNAMICS, Issue 3 2001Gertrud Brachtendorf Abstract Endomucin is a recently identified sialomucin that is specifically expressed on endothelium of the adult mouse. Here, we have analysed the expression of endomucin during development of the vascular system by immunohistochemistry by using three monoclonal antibodies (mAb). We demonstrate that two of the mAb, V.5C7 and V.1A7, recognize epitopes on the nonglycosylated protein, because they recognize the antigen when it is synthesized as a bacterial fusion protein and when it is in vitro translated in a membrane-free reticulocyte lysate. During in vitro differentiation of embryonic stem cells to endothelial cells, endomucin is expressed at day 6 after onset of differentiation, 1 day later than PECAM-1. During differentiation of the mouse embryo, endomucin is first detected at E8.0 in all embryonic blood vessels detectable at this stage but is absent in blood islands of the yolk sac. Analysing the paraaortic-splanchnopleura (P-SP) region and the aorta-gonad-mesonephros (AGM) region as sites of intraembryonic hematopoiesis, we found that endothelium of the dorsal aorta is brightly positive for endomucin at E8.5,9.0 and at E11.5. At later stages and in the adult aorta, endothelial staining is strongly reduced and confined to focal areas. Cell clusters associated with the luminal surface of the endothelium of the dorsal aorta could be stained for endomucin and for CD34. At a later stage (E15.5) single leukocytes in the lumen of large venules were stained for endomucin. We conclude that endomucin is an early endothelial-specific antigen that is also expressed on putative hematopoietic progenitor cells. © 2001 Wiley-Liss, Inc. [source] ENDOSCOPIC IDENTIFICATION OF HELICOBACTER PYLORI GASTRITIS IN CHILDRENDIGESTIVE ENDOSCOPY, Issue 2 2010Nao Hidaka Aim:, The role of endoscopic findings in deciding whether to biopsy the gastric mucosa of children remains unclear. The present study attempted, for the first time, to identify the value of endoscopic features for diagnosis of Helicobacter pylori (Hp) infection in children. Methods:, Hp status of consecutive children receiving esophagogastroduodenoscopy (EGD) was established by combinations of histology, 13C-urea breath test, and serum Hp immunoglobulin (Ig)G antibody. After routine EGD using a conventional endoscope, the presence of RAC (regular arrangement of collecting venules) was scored by close observation, which was carried out at two sites of lower corpus lesser curvature and upper corpus greater curvature. RAC-positive was defined as the presence of minute red points in a regular pattern. Antral nodularity was also scored as present/absent. Results:, Eighty-seven consecutive children (38 boys, median age 13 years, range 9,15 years) were evaluated; 25 (29%) were Hp positive. Antral nodularity was seen in 21 (84%) all of whom were Hp positive. The RAC-negative pattern based on examination of the upper and lower corpus yielded a sensitivity, specificity, positive predictive value and negative predictive value for the presence of Hp infection of 100%, 90%, 81%, and 100%. Magnifying endoscopy confirmed that the RAC pattern corresponded to collecting venules in the gastric corpus. Conclusions:, The absence of RAC pattern suggests that gastric mucosa biopsies should be taken despite otherwise normal-appearing gastric mucosa for the diagnosis of Hp infection in children. [source] ENDOSCOPIC MICROVASCULAR ARCHITECTURE OF THE PORTAL HYPERTENSIVE GASTRIC MUCOSA ON NARROW BAND IMAGINGDIGESTIVE ENDOSCOPY, Issue 3 2007Seishu Hayashi Background:, We evaluated the endoscopic microvascular architecture of the gastric mucosa in portal hypertension patients using the prototype of narrow band imaging (NBI). Material and Methods:, The study included 103 Helicobacter pylori -negative patients with chronic liver disease (22 without portal hypertension (group 1), 81 with portal hypertension (group 2)). Results:, (i) Abnormality of collecting venules, reddening mucosa, red spots, a mosaic-like pattern, and gastric antral vascular ectasia (GAVE) were observed on the gastric mucosa, and an obscure change in collecting venules (73% vs 14%; P < 0.001), reddening mucosa (49% vs 5%; P < 0.001), red spots (36% vs 5%; P < 0.01) and a mosaic-like pattern (40% vs 5%; P < 0.01) were more frequently observed in group 2 than in group 1. (ii) On magnifying endoscopy with NBI, the mucosa with an obscure change in collecting venules was demonstrated as dilation of the capillaries surrounding the gastric pits in various degrees, and reddening mucosa was observed as extended and swollen gastric pits and various degrees of dilated and convoluted capillaries surrounding the gastric pits. Red spots were demonstrated as extended and swollen gastric pits, dilated and convoluted capillaries surrounding the gastric pits, and intramucosal hemorrhage around these capillaries. GAVE was recognized as partial and marked dilatation of the capillaries surrounding the gastric pits. Conclusion:, Abnormality of collecting venules, swelling of gastric pits, dilatation of capillaries surrounding the gastric pits, intramucosal hemorrhage around capillaries, and partial and marked dilatation of the capillaries were observed on the gastric mucosa in portal hypertension patients. [source] Circulation in normal and inflamed dental pulpENDODONTIC TOPICS, Issue 1 2007ELLEN BERGGREEN In the pulp, arteries branch into a capillary network before they leave the pulp as venules through the apical foramina. The tissue has low compliance, as it is enclosed in dentin, and has a relatively high blood flow and blood volume. The interstitial fluid pressure (IFP) and colloid osmotic pressure are relatively high whereas the net driving blood pressure is low. The high pulsatile IFP is probably the major force for propelling lymph in the dental pulp. Vasodilation in neighboring tissue as well as arteriovenous (AV) shunts in the pulp itself can contribute to a fall in total and coronal pulpal blood flow, respectively. The pulp blood flow is under nervous, humoral, and local control. Inflammatory vascular responses, vasodilation, and increased vessel permeability induce an increase in IFP that can be followed by a temporarily impaired blood flow response. Lipopolysaccharides (LPS) from bacteria may cause endothelial activation in the pulp, leading to vasoconstriction and reduced vascular perfusion. Lymphatic vessels are identified with specific lymphatic markers in the pulp but so far, little is known about their function. Because of the special circulatory conditions in the pulp, there are several clinical implications that need to be considered in dental treatment. Received 13 February 2009; accepted 28 August 2009. [source] The polysaccharide fucoidan inhibits microvascular thrombus formation independently from P- and l -selectin function in vivoEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2000Thorlacius Background Adhesion molecules of the selectin family (mainly P- and L-selectin) have been suggested to mediate interactions between platelets, leukocytes and endothelial cells in thrombus formation. The polysaccharide fucoidan has anticoagulative properties, but is also able to bind and block the function of the selectins. Here, we investigated in vivo (i) if fucoidan can prevent microvascular thrombus formation, and (ii) whether this is potentially mediated by the inhibition of P-and/or L-selectin. Materials and Methods For this purpose, we used intravital microscopy in the mouse cremaster microcirculation in which thrombosis was induced photochemically by light exposure to individual arterioles and venules after intravenous (i.v.) injection of FITC-dextran. Results We found that intravenous administration of fucoidan significantly prolonged the time required for complete occlusion in arterioles and venules by almost seven- and nine-fold, respectively. In contrast, treatment with monoclonal antibodies against P- and L-selectin had no effect on the development of microvascular thrombosis. Fucoidan and also the anti-P-selectin antibody completely inhibited baseline venular leukocyte rolling in the cremaster muscle, indicating that these treatment regimes abolished P-selectin function. Importantly, fucoidan and the anti-P-selectin antibody had no effect on systemic platelet and leukocyte counts. On the other hand, we found that fucoidan treatment significantly altered coagulation parameters, including prothrombin time (Quick percentage), activated partial thromboplastin time (APTT) and thrombin clotting time (TCT), which may explain the potent in vivo anticoagulative effect of fucoidan observed here. Conclusions Taken together, our novel findings suggest that fucoidan effectively prevents microvascular thrombus formation induced by endothelial damage in arterioles and venules in vivo. This protective effect of fucoidan is not attributable to inhibition of P- and L -selectin function but may instead be related to the anticoagulative capacity of fucoidan. [source] T lymphocyte rolling and recruitment into peripheral lymph nodes is regulated by a saturable density of L-selectin (CD62L)EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2007Elena Galkina Dr. Abstract L-selectin mediates tethering and rolling of lymphocytes in high endothelial venules (HEV) of lymph nodes (LN) and of leukocytes at inflammatory sites. We used transgenic mice expressing varying levels of wild-type or a non-cleavable mutant form of L-selectin on T cells to determine the relationship between L-selectin density, tethering and rolling, and migration into LN. T cells expressing supraphysiological levels of either wild-type or non-cleavable L-selectin showed rolling parameters similar to C57BL/6 T cells in hydrodynamic flow assays and during rolling in Peyer's patch HEV. In contrast, PMA- or antigen-activated T cells and L-selectin+/, T cells expressing subphysiological levels of L-selectin showed reduced numbers of rolling cells with increased rolling velocity. Short-term homing studies showed that elevated expression of L-selectin above physiological levels had no effect on T cell migration to LN; however, low L-selectin expression resulted in reduced T cell homing to LN. Thus, T lymphocyte migration into LN is regulated by the density of cell surface L-selectin. In addition, there is a saturable density of L-selectin required for optimal homing to PLN in C57BL/6 mice, the L-selectin level on circulating naive T cells promotes optimal homing, and increased expression above saturating levels promotes no further increase in T cell recruitment. [source] Comparison of High Resolution Magnifying Endoscopy and Standard Videoendoscopy for the Diagnosis of Helicobacter pylori Gastritis in Routine Clinical Practice: A Prospective StudyHELICOBACTER, Issue 1 2009Can Gonen Abstract Background:, It has been shown that standard endoscopic features often labeled as gastritis has a poor correlation with histopathology. Recently, high resolution magnifying endoscopy has been reported to be an effective method to diagnose gastritis. The aim of the present study was to compare standard endoscopy with magnifying endoscopy for the diagnosis of Helicobacter pylori gastritis, and to determine whether gastritis can be diagnosed based on findings at magnification endoscopy. Materials and Methods:, A total of 129 patients were enrolled into the study. Erythema, erosions, prominent area gastrica, nodularity, and regular arrangement of collecting venules (RAC) were investigated by standard endoscopy. Standard endoscopy was followed by magnifying endoscopy in all patients, and repeated in 55 patients after indigo carmine spraying. Results:, None of the standard endoscopic features showed a sensitivity of more than 70% for H. pylori gastritis, except RAC pattern analysis. Absence of a corporal RAC pattern had 85.7% sensitivity and 82.8% specificity for predicting H. pylori infection. Under magnification, the sensitivity and specificity of regular corporal pattern (regular collecting and capillary vascular structures with gastric pits resembling pinholes) for predicting normal histology were 90.3% and 93.9%, respectively. Loss of collecting venules, or both collecting and capillary structures was correlated with chronic inflammation and activity. With the progression of mucosal atrophy, irregular collecting venules became visible. The values for irregularly arranged antral ridge pattern for the prediction of antral gastritis were 89.3% and 65.2%, respectively. Indigo carmine staining increased sensitivity and specificity up to 97.6% and 100% for corporal gastritis, and up to 88.4% and 75.0% for antral gastritis, respectively. Indigo carmine staining significantly increases the detection of intestinal metaplasia. Conclusions:, High resolution magnifying is superior to standard endoscopy for the diagnosis of H. pylori gastritis, and identification of specific histopathologic features such as atrophy and intestinal metaplasia seems possible. [source] Discrimination of Normal Gastric Mucosa from Helicobacter pylori Gastritis using Standard Endoscopes and a Single Observation Site: Studies in Children and Young AdultsHELICOBACTER, Issue 2 2004Yoshiko Nakayama ABSTRACT Background., In the Helicobacter pylori -negative normal stomach, collecting venules are visible in the gastric corpus as numerous minute points. This finding has been termed ,regular arrangement of collecting venules' (RAC). The aim of the present study was to investigate the reliability of the presence of the RAC pattern for discrimination of normal gastric mucosa from H. pylori gastritis in pediatric patients. Methods., Fifty-two consecutive children, adolescents and young adults (male:female 24 : 28; median age 15 years, range 8,29 years) referred for endoscopy and assessed for H. pylori infection were prospectively studied. The lower lesser curvature of the corpus near the incisura was evaluated for the RAC pattern using a standard endoscope with the tip close to, but not in contact with, the gastric surface. Gastric biopsies were taken after the endoscopic observation. Results., In all the 29 RAC-positive patients, active H. pylori gastritis was absent, whereas H. pylori gastritis was found in 20 of 23 RAC-negative patients (86.9%). Conclusions., Identification of the RAC pattern at the lower lesser curvature of the corpus using close observation with a standard endoscope proved to be an effective and practical marker to discriminate normal histology from H. pylori gastritis among both children and young adults. Absence of the RAC pattern should prompt gastric mucosal biopsies despite otherwise normal-appearing gastric mucosa. [source] Induction of cellular resistance against Kupffer cell,derived oxidant stress: A novel concept of hepatoprotection by ischemic preconditioningHEPATOLOGY, Issue 2 2003Rolf J. Schauer Ischemic preconditioning (IP) triggers protection of the liver from prolonged subsequent ischemia. However, the underlying protective mechanisms are largely unknown. We investigated whether and how IP protects the liver against reperfusion injury caused by Kupffer cell (KC)-derived oxidants. IP before 90 minutes of warm ischemia of rat livers in vivo significantly reduced serum alanine aminotransferase (AST) levels and leukocyte adherence to sinusoids and postsinusoidal venules during reperfusion. This protective effect was mimicked by postischemic intravenous infusion of glutathione (GSH), an antioxidative strategy against KC-derived H2O2. Interestingly, no additional protection was achieved by infusion of GSH to preconditioned animals. These findings and several additional experiments strongly suggest IP mediated antioxidative effects: IP prevented oxidant cell injury in isolated perfused rat livers after selective KC activation by zymosan. Moreover, IP prevented cell injury and pertubations of the intracellular GSH/GSSG redox system caused by direct infusion of H2O2 (0.5 mmol/L). IP-mediated resistance against H2O2 could neither be blocked by the adenosine A2a antagonist DMPX nor mimicked by A2a agonist CGS21680. In contrast, H2O2 resistance was abolished by the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580, but induced when p38 MAPK was directly activated by anisomycin. In conclusion, we propose a novel concept of hepatoprotection by IP: protection of liver cells by enhancing their resistance against KC-derived H2O2. Activation of p38 MAPK and preservation of the intracellular GSH/oxidized glutathione (GSSG) redox system, but not adenosine A2a receptor stimulation, seems to be pivotal for the development of H2O2 resistance in preconditioned livers. [source] Regulatory processes interacting to maintain hepatic blood flow constancy: Vascular compliance, hepatic arterial buffer response, hepatorenal reflex, liver regeneration, escape from vasoconstrictionHEPATOLOGY RESEARCH, Issue 11 2007W. Wayne Lautt Constancy of hepatic blood flow (HBF) is crucial for several homeostatic roles. The present conceptual review focuses on interrelated mechanisms that act to maintain a constant HBF per liver mass. The liver cannot directly control portal blood flow (PF); therefore, these mechanisms largely operate to compensate for PF changes. A reduction in PF leads to reduced intrahepatic distending pressure, resulting in the highly compliant hepatic vasculature passively expelling up to 50% of its blood volume, thus adding to venous return, cardiac output and HBF. Also activated immediately upon reduction of PF are the hepatic arterial buffer response and an HBF-dependent hepatorenal reflex. Adenosine is secreted at a constant rate into the small fluid space of Mall which surrounds the terminal branches of the hepatic arterioles, portal venules and sensory nerves. The concentration of adenosine is regulated by washout into the portal venules. Reduced PFreduces the washout and the accumulated adenosine causes dilation of the hepatic artery, thus buffering the PF change. Adenosine also activates hepatic sensory nerves to cause reflex renal fluid retention, thus increasing circulating blood volume and maintaining cardiac output and PF. If these mechanisms are not able to maintain total HBF, the hemodynamic imbalance results in hepatocyte proliferation, or apoptosis, by a shear stress/nitric oxide-dependent mechanism, to adjust total liver mass to match the blood supply. These mechanisms are specific to this unique vascular bed and provide an excellent example of multiple integrative regulation of a major homeostatic organ. [source] Structure, lymphatic vascularization and lymphocyte migration in mucosa-associated lymphoid tissueIMMUNOLOGICAL REVIEWS, Issue 1 2003Giacomo Azzali Summary:, In this review, we consider the morphological aspects and topographical arrangement of gut-associated lymphoid tissue (GALT) (solitary and aggregate lymph nodules or Peyer's patches) and of vermiform appendix in the human child and in some mammals. The spatial arrangement of the vessels belonging to apparatus lymphaticus periphericus absorbens (ALPA) and of blood vessels within each lymphoid follicle as well as the ultrastructural characteristics of the lymphatic endothelium with high absorption capacity are considered. Particular attention is also paid to the morphological and biomolecular mechanisms inducing lymphocyte transendothelial migration to the bloodstream by means of lymphatic vessels as well as their passage from blood into lymphoid tissue through the high endothelial venules (HEVs). The preferential transendothelial passage of lymphocytes and polymorphonuclear neutrophils within ALPA vessels of the interfollicular area does not occur following the opening of intercellular contacts, but rather it occurs by means of ,intraendothelial channels'. In HEVs, on the contrary, the hypothesis is plausible that lymphocyte transendothelial migration into lymphoid tissue occurs through a channel-shaped endothelial invagination entirely independent of interendothelial contacts. The lymph of ALPA vessels of the single Peyer's patch is conveyed into precollector lymphatic vessels and into prelymph nodal collectors, totally independent of the ALPA vessels of the gut segments devoid of lymphoid tissue. The quantitative distribution of T lymphocytes in the lymph of mucosal ALPA vessels suggests a prevalent function of fluid uptake, whereas a reservoir and supply function is implicated for the vessels of interfollicular area. The precollector lymphatic vessels and prelymph nodal collectors are considered to be vessels with low absorption capacity, whose main function is lymph conduction and flow. [source] Monocytes in the rat: Phenotype and function during acute allograft rejectionIMMUNOLOGICAL REVIEWS, Issue 1 2001Birte Steiniger Summary: Cells of the monocyte/macrophage system originate from the bone marrow, reach the organs via the blood, immigrate through post-capillary venules and further differentiate into organ-specific tissue macrophages. In rats and other species, activated monocytes/macrophages aggravate autoimmune reactions, rejection of non-vascularized allografts and chronic allograft rejection. It is very likely that they also contribute to acute allograft destruction. So far it has been impossible to distinguish the function of monocytes from that of macrophages, because cell phenotypes and their alterations upon activation are ill-defined. We have thus begun to characterize the ex vivo phenotype and function of rat monocytes in the normal state and during renal allograft rejection. Monocytes are recovered from both the central and the marginal blood pool by perfusing either the recipient's circulation or the allograft vasculature. Rat monocytes have a unique surface phenotype. During allograft rejection or after infusion of interferon-, they up-regulate class II MHC molecules, CD161 (NKR-P1A), CD62L and CD8, while CD4 and CD43 are down-modulated. Activated perfusate monocytes exert increased in vitro cytotoxicity against tumour targets, which differs from that of NK cells. We speculate that activated monocytes contribute to kidney allograft destruction by directly damaging endothelial cells or by promoting intravascular coagulation. [source] The Fps/Fes kinase regulates leucocyte recruitment and extravasation during inflammationIMMUNOLOGY, Issue 4 2007Sean A. Parsons Summary Fps/Fes and Fer comprise a distinct subfamily of cytoplasmic protein-tyrosine kinases, and have both been implicated in the regulation of innate immunity. Previous studies showed that Fps/Fes-knockout mice were hypersensitive to systemic lipopolysaccharide (LPS) challenge, and Fer-deficient mice displayed enhanced recruitment of leucocytes in response to localized LPS challenge. We show here for the first time, a role for Fps in the regulation of leucocyte recruitment to areas of inflammation. Using the cremaster muscle intravital microscopy model, we observed increased leucocyte adherence to venules, and increased rates and degrees of transendothelial migration in Fps/Fes-knockout mice relative to wild-type animals subsequent to localized LPS challenge. There was also a decreased vessel wall shear rate in the post-capillary venules of LPS-challenged Fps/Fes-knockout mice, and an increase in neutrophil migration into the peritoneal cavity subsequent to thioglycollate challenge. Using flow cytometry to quantify the expression of surface molecules, we observed prolonged expression of the selectin ligand PSGL-1 on peripheral blood neutrophils from Fps/Fes-knockout mice stimulated ex vivo with LPS. These observations provide important insights into the observed in vivo behaviour of leucocytes in LPS-challenged Fps/Fes-knockout mice and provide evidence that the Fps/Fes kinase plays an important role in the innate immune response. [source] Down-regulation of endothelial adhesion molecules and leukocyte adhesion by treatment with superoxide dismutase is beneficial in chronic immune experimental colitisINFLAMMATORY BOWEL DISEASES, Issue 10 2005Joaquim Seguí PhD Abstract Modulation of adhesion molecule expression that govern trafficking of leukocytes into the inflamed intestine is envisioned as a new strategy for treatment of inflammatory bowel disease (IBD). This study was designed to determine the impact of reducing oxidative stress on adhesion molecules expression and leukocyte recruitment in experimental chronic colitis. For that purpose, colitic interleukin-10 knockout and wild-type mice were studied. Groups of animals were treated with Cu/Zn superoxide dismutase (SOD1) 13 mg/kg/d or vehicle for either 7 or 14 days. Expression of vascular cell adhesion molecule-1 and mucosal addressin cell adhesion molecule-1 were determined; leukocyte-endothelial cell interactions in colonic venules were studied with intravital microscopy; and changes in colon pathology and biomarkers of colitis severity were determined. Development of colitis was associated with a marked increase in endothelial vascular cell adhesion molecule-1 and mucosal addressin cell adhesion molecule-1 expression, which were significantly reduced by treatment with SOD1. The increase in leukocyte rolling and adhesion in colonic venules of colitic mice were significantly reduced by administration of SOD1. This treatment markedly reduced colonic lipid hydroperoxidation, myeoloperoxidase activity, and plasma levels of serum amyloid A protein and resulted in significant, although modest, reductions in histologic damage score. The therapeutic value of SOD1 when administered prophylactically was assessed in the dextran sulfate sodium model of colitis with similar positive results. These results indicate that SOD1 affords significant amelioration of colonic inflammatory changes in experimental colitis. Down-regulation of adhesion molecule expression, reduction of lipid hydroperoxidation, and recruitment of leukocytes into the inflamed intestine contribute to this beneficial effect. [source] Age-dependent histoarchitectural changes in human lymph nodes: an underestimated process with clinical relevance?JOURNAL OF ANATOMY, Issue 5 2010Catarina Hadamitzky Abstract Experimental evidence indicates that lymph nodes in humans undergo alterations during ageing. This is clinically important because of the crucial role of these organs in the immune system and their lymph reabsorption and drainage function. Although some age-related changes in lymph node histoarchitecture have been described, they are seldom taken into account in traditional depictions of lymph nodes. Recently introduced clinical procedures, such as intranodal vaccination or lymph node transplantation, have demonstrated the need for an accurate knowledge of these degenerative processes. In this study, superficial inguinal lymph nodes were obtained from 41 deceased patients between 17 and 98 years old. To minimize immunological influences, such as chronic diseases, specimens were only obtained from forensic pathology autopsies. An immunohistochemical analysis was carried out, on the basis of which lymph node degeneration was scored according to the numbers of lymphocytes and high endothelial venules, and degree of fibrosis and lipomatosis. We observed an age-dependent tendency towards the replacement of areas populated with diverse immune cells by connective tissue. Paradoxically, these changes were also detected in some of the nodes from younger age groups. In conclusion, lymph nodes can display degenerative changes that are mainly age-related and often diverge from the common description found in textbooks. These alterations should be taken into account when dealing with lymph nodes diagnostically and therapeutically in clinical practice. [source] Endotoxin translocation in two models of experimental acute pancreatitisJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2003C. Vasilescu Abstract To test the hypothesis that endotoxin is absorbed from the gut into the circulation in rats with experimental acute pancreatitis we studied two different animal models. In the first model necrotizing pancreatitis was induced by the ligation of the disatl bilio-pancreatic duct while in the second, experimental oedematous acute pancreatitis was induced by subcutaneous injections of caerulein. In both experiments, in the colon of rats with acute pancreatitis endotoxin from Salmonella abortus equi was injected. Endotoxin was detected by immunohistochemistry in peripheral organs with specific antibodies. The endotoxin was found only in rats with both acute pancreatitis and endotoxin injected into the colon and not in the control groups. The distribution of endotoxin in liver at 3 and 5 days was predominantly at hepatocytes level around terminal hepatic venules, while in lung a scattered diffuse pattern at the level of alveolar macrophages was identified. A positive staining was observed after 12 hours in the liver, lung, colon and mesenteric lymph nodes of rats with both caerulein pancreatitis and endotoxin injected into the colon. We conclude that the experimental acute pancreatitis leads to early endotoxin translocation from the gut lumen in the intestinal wall and consequent access of gut-derived endotoxin to the mesenteric lymph nodes, liver and lung. [source] Characteristic endoscopic and magnified endoscopic findings in the normal stomach without Helicobacter pylori infectionJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 1 2002KAZUYOSHI YAGI Abstract Background and Aims: The aim of this study was to clarify the endoscopic features of the Helicobacter pylori (H. pylori) -free stomach by examining the arrangement of minute points visible on the corpus. Since these points were clarified by magnifying endoscopy as collecting venules, this finding was termed ,regular arrangement of collecting venules (RAC)'. The findings from more endoscopic studies are presented and the differences between magnified views of the normal and H. pylori -infected corpus and antrum are described in particular. Methods: The study group consisted of 557 patients who were subjected to endoscopy and checked for H. pylori. The RAC in each patient was assessed. Magnifying endoscopy in 301 patients was used to examine the corpus and in 94 patients to examine the antrum. Results: One hundred and fifty-eight patients had normal stomachs without H. pylori. We diagnosed 389 patients with H. pylori gastritis. In 10 patients H. pylori was not detected, but inflammation was present. Of the 158 patients with H. pylori -negative normal stomachs, 151 had RAC. As a determinant of the normal stomach without H. pylori infection, the presence of RAC had 93.8% sensitivity and 96.2% specificity. All 30 patients with H. pylori -negative normal stomachs had a well-defined ridge pattern (wDRP) on the antrum as observed under magnifying endoscopy. As a determinant of the normal stomach without H. pylori infection, wDRP had a specificity of 100%, but a sensitivity of only 54.5%. Conclusions: The presence of RAC is characteristic of a normal stomach without H. pylori. Magnified views of the normal antrum were different from that of the normal corpus. [source] Ranking the contributing risk factors in venous thrombosis in terms of therapeutic potential: Virchow's triad revisitedJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 2 2006Masaki Kiyomura Abstract Aim: Thromboemoblism is an attendant feature of a variety of pathological conditions. We reconsidered Virchow's pathogenetic triad of stasis, humoral factors and vascular wall pathologies in the light of platelet behavior in vivo. Methods: Rat mesenteric microcirculation was examined by intravital microscopy. After isolated rat platelets had been injected i.v. into rats, their behavior in venules was examined under the following conditions: stasis from pressure, hemoconcentration from erythropoietin injections, or endothelial damage from tumor necrosis factor-,. Results: In the endothelial damage group, platelets displayed transient adhesion and rolling, while some platelets exhibited stationary adhesion to venular endothelium. The stasis and hemoconcentration groups exhibited only a slight change in adhesive response. Conclusion: Endothelial dysfunction appears to be the most important contributing factor in the development of venous thrombosis. As such, targeting this dysfunction is suggested for therapeutic intervention. [source] Polymicrobial sepsis and endotoxemia promote microvascular thrombosis via distinct mechanismsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2010K. N. PATEL Summary.,Background:,We reported recently that endotoxemia promotes microvascular thrombosis in cremaster venules of wild-type mice, but not in mice deficient in toll-like receptor 4 (TLR4) or von Willebrand factor (VWF). Objective:,To determine whether the clinically relevant model of polymicrobial sepsis induced by cecal ligation/perforation (CLP) induces similar responses via the same mechanisms as endotoxemia. Methods:,We used a light/dye-injury model of thrombosis in the cremaster microcirculation of wild-type mice and mice deficient in toll-like receptor-4 (C57BL/10ScNJ), toll-like receptor 2 (TLR2), or VWF. Mice underwent CLP or sham surgery, or an intraperitoneal injection of endotoxin (LPS) or saline. In the CLP model, we assessed the influence of fluid replacement on thrombotic responses. Results:,Both CLP and LPS enhanced thrombotic occlusion in wild-type mice. In contrast to LPS, CLP enhanced thrombosis in TLR4- and VWF-deficient strains. While TLR2-deficient mice did not demonstrate enhanced thrombosis following CLP, LPS enhanced thrombosis in these mice. LPS, but not CLP, increased plasma VWF antigen relative to controls. Septic mice, particularly those undergoing CLP, developed significant hemoconcentration. Intravenous fluid replacement with isotonic saline prevented the hemoconcentration and prothrombotic responses to CLP, though fluids did not prevent the prothrombotic response to LPS. Conclusions:,Polymicrobial sepsis induced by CLP and endotoxemia promote microvascular thrombosis via distinct mechanisms; enhanced thrombosis induced by CLP requires TLR2 but not TLR4 or VWF. The salutary effects of intravenous fluid replacement on microvascular thrombosis in polymicrobial sepsis remain to be characterized. [source] Formation of platelet strings and microthrombi in the presence of ADAMTS-13 inhibitor does not require P-selectin or ,3 integrinJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 3 2007A. K. CHAUHAN Summary. Background:,Ultra-large von Willebrand factor (ULVWF) and the receptor P-selectin are released from endothelial Weibel,Palade bodies during injury or inflammation. VWF mediates platelet adhesion and P-selectin promotes leukocyte rolling. ADAMTS-13 limits the duration of platelet adhesion by cleaving the ULVWF. In the absence of ADAMTS-13, long VWF filaments decorated with platelets form. Recent in vitro studies suggested that P-selectin might anchor these platelet strings to endothelium, but whether the same mechanism exists in vivo remains to be elucidated. Methods:,We address the role of P-selectin and ,3 integrin in platelet string formation in vivo using intravital microscopy by infusing inhibitory ADAMTS-13 antibody in P-selectin-/- and ,3 -deficient mice and activating the endothelium by injecting histamine. Results:,We show that inhibition of ADAMTS-13 combined with endothelial activation leads to similar extents of platelet string formation in wild-type, P-selectin- and integrin ,3 -deficient mice. Further, in venules the platelet strings can coalesce into VWF-platelet aggregates. This process utilizes neither the platelet ,3 integrin nor P-selectin. We also show in vitro that platelets can act as a bridge between the VWF fibers and that VWF can self-associate even in areas devoid of platelets. Conclusions:,The formation or retention of the platelet strings does not require P-selectin or the endothelial VWF receptor ,v,3. Furthermore, in the presence of low ADAMTS-13 activity, VWF-dependent and ,IIb,3 -independent platelet clustering occurs in veins, as has been shown at high arterial shear rates. Our study further supports the importance of regulation of VWF multimer size upon secretion from Weibel,Palade bodies. [source] | ||||||||||||||||||||||||||||||||||