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Effect of C3a and C5a anaphylatoxins on guinea-pig isolated blood vessels.

Four major guinea-pig blood vessels were isolated and studied in vitro for their contractile responses to anaphylatoxins C3a and C5a. Both peptides were assayed in the 10(-9) to 10(-7) M range and their effects were parallel, although C3a was less potent and more tachyphylactic than C5a. The most responsive blood vessel, relative to a histamine maximal response, was the portal vein, followed by the pulmonary artery and the thoracic aorta. The abdominal vena cava did not respond to either C3a or C5a. Participation of secondary mediators in the vasoconstrictor effect of C3a and C5a was assessed by exposing portal veins and pulmonary arteries to specific inhibitors. The four drugs were: indomethacin, a cyclooxygenase inhibitor; pyrilamine, an antagonist of H1 receptors for histamine; FPL55712, an antagonist of the leukotriene component of slow-reacting substance of anaphylaxis; and phentolamine, an alpha adrenergic blocker. This pharmacological analysis suggests that prostaglandin-like substances mediate most of the anaphylatoxin vasoconstrictor effects, with a biologically significant participation of leukotrienes in the case of C3a and histamine in the case of C5a. High variability between individual tissue responses to the anaphylatoxins was investigated in terms of previous exposure to activated complement. Cobra venom factor (200 micrograms) was injected i.v. in five guinea pigs 2 hr before sacrifice. This treatment reduced the serum concentration of C3 and C5 to 9 and 32%, respectively, as compared with saline-treated animals. The portal vein excised from the cobra venom factor-treated animals exhibited reduced sensitivities to C3a, but showed normal response to C5a. The selective desensitization to C3a after complement activation in vivo is presumably related to the highly tachyphylactic effect of C3a on blood vessels.

Anaphylatoxins↗

[Development of blood vessels in the human eyeball].

Blood vessels of 167 eyeballs of human embryos and fetuses have been studied, using macro- microscopical, histological and morphometrical methods. Time of appearance and differentiation of blood vessels in the eye anlage has been determined. Topography and architecture of the vitreous body artery are described in detail, as well as the vascular tunic of the lens and the pupil membrane. Regularities and time of reversal development of the vascular formations mentioned are followed during the whole intrauterine development. The data obtained add to extend our knowledge on the role of disturbances of the normal morphogenesis of the eyeball blood bed in pathogenesis of its congenital diseases.

Arteries↗

Myogenic Akt signaling regulates blood vessel recruitment during myofiber growth.

Blood vessel recruitment is an important feature of normal tissue growth. Here, we examined the role of Akt signaling in coordinating angiogenesis with skeletal muscle hypertrophy. Hypertrophy of C2C12 myotubes in response to insulin-like growth factor 1 or insulin and dexamethasone resulted in a marked increase in the secretion of vascular endothelial growth factor (VEGF). Myofiber hypertrophy and hypertrophy-associated VEGF synthesis were specifically inhibited by the transduction of a dominant-negative mutant of the Akt1 serine-threonine protein kinase. Conversely, transduction of constitutively active Akt1 increased myofiber size and led to a robust induction of VEGF protein production. Akt-mediated control of VEGF expression occurred at the level of transcription, and the hypoxia-inducible factor 1 regulatory element was dispensable for this regulation. The activation of Akt1 signaling in normal mouse gastrocnemius muscle was sufficient to promote myofiber hypertrophy, which was accompanied by an increase in circulating and tissue-resident VEGF levels and high capillary vessel densities at focal regions of high Akt transgene expression. In a rabbit hind limb model of vascular insufficiency, intramuscular activation of Akt1 signaling promoted collateral and capillary vessel formation and an accompanying increase in limb perfusion. These data suggest that myogenic Akt signaling controls both fiber hypertrophy and angiogenic growth factor synthesis, illustrating a mechanism through which blood vessel recruitment can be coupled to normal tissue growth.

Animals↗

Sturge-Weber syndrome: altered blood vessel fibronectin expression and morphology.

Sturge-Weber syndrome presents with vascular malformations of the brain, skin, and eye. Fibronectin has potent effects on angiogenesis, vessel remodeling, and vessel innervation density. To determine fibronectin expression in the blood vessels of Sturge-Weber syndrome brain and skin tissue and to quantify the density and circumference of Sturge-Weber syndrome blood vessels by type compared with controls, we performed in situ hybridization for fibronectin messenger ribonucleic acid (RNA) expression on six Sturge-Weber syndrome cortical brain samples, six epilepsy brain samples, skin from two port-wine stain skin lesions, and two normal skin samples from two subjects with Sturge-Weber syndrome. Fibronectin messenger RNA was expressed in blood vessels and endothelial cells in the parenchyma of both Sturge-Weber syndrome and control brain tissues and in skin samples. Fibronectin expression was significantly reduced by 23% in the Sturge-Weber syndrome meningeal vessels compared with the epilepsy controls (P < .01). Fibronectin expression was significantly increased by 19% in the Sturge-Weber syndrome parenchymal vessels compared with the epilepsy controls (P < .05). No difference was found in the expression of fibronectin in port-wine stain skin blood vessels. The density of leptomeningeal blood vessels in the Sturge-Weber syndrome brain tissue samples was 45% greater than in the epilepsy samples (P < .05). Blood vessel circumference was significantly decreased in the Sturge-Weber syndrome meningeal vessels compared with the controls (27%; P < .05). When blood vessels from different brain regions were compared, fibronectin expression was decreased in Sturge-Weber syndrome meningeal vessels and was increased in the parenchymal vessels. Altered blood vessel fibronectin expression in Sturge-Weber syndrome could contribute to abnormal vascular structure and function in this disorder.

Brain↗

Tissue engineering: creation of long-lasting blood vessels.

The construction of stable blood vessels is a fundamental challenge for tissue engineering in regenerative medicine. Although certain genes can be introduced into vascular cells to enhance their survival and proliferation, these manipulations may be oncogenic. We show here that a network of long-lasting blood vessels can be formed in mice by co-implantation of vascular endothelial cells and mesenchymal precursor cells, by-passing the need for risky genetic manipulations. These networks are stable and functional for one year in vivo.

Animals↗

Blood vessel implantation into ischemic bone.

Blood vessel implantation, core decompression, and core decompression plus cancellous bone grafting were compared in 36 adult mongrel dogs to evaluate their relative effectiveness in revascularizing an ischemic femoral head. Each of the methods resulted in a reversal of the ischemic changes to varying degrees. Blood vessel implantation resulted in increased new bone formation at the site of vessel implantation but no significant revascularization in the peripheral portion of the femoral head. The method of creating avascular necrosis of the femoral head of the canine, as described by Hori, was studied in a controlled fashion. Although ischemic changes were noted in our hands, the model failed to produced findings consistent with avascular necrosis.

Angiography↗

Prevalence, morphology, and topography of blood vessels in herniated disc tissue. A comparative immunocytochemical study.

STUDY DESIGN: Ninety disc herniations removed during surgery were studied by immunocytochemistry, using two different endothelial cell markers, to study the prevalence, morphology, and topography of blood vessels in disc herniations. OBJECTIVES: To increase the specific localization of even very small blood vessels present in disc herniations by using specific antibodies to endothelial cells; to study blood vessels comparatively with two different endothelial cell antibodies, comparing their prevalence; and to study blood vessel morphology and topographic relationships of blood vessels to other tissue elements, particularly disc cells. SUMMARY OF BACKGROUND DATA: In many previous macroscopic studies and in studies using conventional histologic methodology, blood vessels have been observed in degenerated and injured intervertebral discs. In a smaller patient sample, the authors previously observed blood vessels in approximately 80% of disc herniations by immunocytochemistry, the blood vessels co-localizing with macrophage cells. Many of these blood vessels are the product of very active neovascularization after disc tissue injury. The presence of such blood vessels has not, however, been studied in greater detail or in larger patient samples. Immunocytochemistry offers superior visualization and more specific localization and was thus used in the present study. METHODS: Thin frozen sections from 90 disc herniations were immunostained in parallel with von Willebrand factor and Ulex europaeus antibodies, both of which localize endothelial cells specifically. Indirect immunocytochemistry by avidin-biotin-peroxidase complex or alkaline phosphatase-antialkaline phosphatase were used for immunolocalization. Blood vessels were classified as being: +, abundant: (+), very few; or +, totally absent. RESULTS: The prevalence of blood vessels in disc herniations was found in 82 of 90 (91%) disc herniations with von Willebrand factor antibody and in 75 of 90 (83%) disc herniations with Ulex europaeus antibody. In 59 disc herniations (66%), blood vessels were observed with both antibodies in parallel, whereas they were observed with neither antibody in only six of 90 disc herniations. Furthermore, the ratio of abundant to very few blood vessels was 73:9 with von Willebrand factor antibody and 63:12 with Ulex europaeus antibody, further supporting the abundance of blood vessels in disc herniations. Blood vessels were most prevalent in sequestrated discs, but they were also observed in six of eight protrusions. Dense blood vessel networks were observed to penetrate the disc tissue, and blood vessels were also present in areas of inflammatory cell infiltration. Topographically, blood vessels were, on several occasions and with both antibodies, seen to pass close by or to surround disc cells. CONCLUSIONS: By immunocytochemistry with endothelial cell markers, blood vessels can be observed to be numerous, and their prevalence in herniated discs is very high, presumably as a result of a very intense neovascularization process after the disc injury. A close apposition to disc cells may suggest attempts to increase the nutrition of these cells and will influence the metabolism of the cells.

Adolescent↗

The effect of surgery and severe injury on blood vessels.

This paper evolves from our previous work that developed a blood vessel model based on the way in which the total tension within the blood vessel wall varies with pressure due to the interaction of specific ions. We use the previous outcomes to examine the diameter of rat middle cerebral arteries (MCAs) as a function of pressure. The MCAs were isolated at 2 h, 1 and 5 days following sham injury and severe traumatic brain injury (TBI). First, we are able to quantify the diameter versus pressure curve in a way that yields three parameters. One of these parameters is the diameter at zero pressure that incorporates properties of the blood vessel walls and the vascular smooth muscle cells. The other two parameters are associated with the myogenic response and the myogenic tone. These parameters enable us to characterize, from the MCAs as a function of pressure in a calcium buffer, each blood vessel into one of three distinct distributions. One of these distributions reflects the optimum conditions. From our data with our blood vessel model, we demonstrate the effect of sham injury on the way in which blood vessels respond to pressure change that appears to recover over time with a half-life of about 40 h. In contrast, severe TBI greatly affects the blood vessel with no indication of recovery over the five-day monitoring period.

Animals↗

Combined conventional transmission, scanning, and high-voltage electron microscopy of the same blood vessel for the study of targeted inflammatory cells in blood-brain barrier inflammation.

The microvasculature of brains and spinal cords from mice subjected to chronic relapsing experimental autoimmune encephalomyelitis (CREAE) was studied using three different electron microscopic techniques. Blood vessels were initially examined by scanning electron microscopy. This allowed for the investigation of topographical changes of the luminal aspects of endothelial cells (ECs) and identification of targeted inflammatory cells (ICs) attached to the ECs. The same blood vessel areas with attached ICs examined by scanning electron microscopy were subsequently trimmed, processed for routine conventional transmission electron microscopy, and plastic embedded. Thin (80 nm) sections were cut and evaluated. Semithick (0.5-0.75 microns) serial sections of this material were examined by high-voltage electron microscopy. Data presented here described a useful technique for combining several ultrastructural techniques that permits simultaneous topographic and cross-sectional examination of selected regions of individual blood vessels or specifically targeted ICs.

Animals↗

[Human chagasic placenta: structural and cytochemical changes of blood vessels].

Various authors have demonstrated that coronary blood vessels could have some participation in the pathogenesis of the cardiac alterations of Chagas' disease. The purpose of this work was to detect structural and cytochemical modifications of blood vessels in human chagasic placentas at term with optical and electron microscopy due their possible participation in the pathogenesis of the congenital transmission of the disease. In two of the six chagasic placentas at term from pregnant women with positive serology, there was diminution and occlusion of the lumen of the chorionic villi blood vessels, with hialine aspect of their walls. An increase of acid phosphatase activity in the endothelium was also observed with electron microscopy. The diminished blood vessel lumen could be due to smooth muscle and endothelium participation.

Chagas Disease↗

Determination of the mechanical properties of the different layers of blood vessels in vivo.

The structure and materials of the blood vessel wall are layered. This article presents the principle of a method to determine the mechanical properties of the different layers in vivo. In vivo measurement begets in vivo data and avoids pitfalls of in vitro tests of dissected specimens. With the proposed method, we can measure vessels of diameters 100 microns and up and obtain data on vascular smooth muscles and adventitia. To derive the full constitutive equations, one must first determine the zero-stress state, obtain the morphometric data on the thicknesses of the layers, and make mechanical measurements in the neighborhood of the zero-stress state. Then eight small perturbation experiments are done on earth blood vessel in vivo to determine eight incremental elastic moduli of the two layers of the blood vessel wall. The calculation requires the morphometric data and the location of the neutral axis. The experiments are simple, the interpretation is definitive, but the analysis is somewhat sophisticated. The method will yield results that are needed to assess the stress and strain in the tissues of the blood vessel. The subject is important because blood vessels remodel themselves significantly and rapidly when their stress and strain deviate from their homeostatic values, and because cell proliferation, differentiation, adhesion, contraction, and locomotion depend on stress and strain in the tissue.

Animals↗

Preoperative assessment of blood vessel involvement in patients with pancreatic cancer.

The major prerequisite for resection of a pancreatic tumor is non-involvement of large blood vessels. Preoperative assessment of blood vessel infiltration may prevent unnecessary surgery. The aim of our study was to investigate the accuracy of endoscopic ultrasonography (EUS) in diagnosis of pancreatic cancer and in preoperative staging. Thirteen patients (7 females, 6 males; mean age 64 years) with a pancreatic tumor, but no evidence of distant metastases, underwent EUS and computerized tomography (CT) in order to assess blood vessel involvement by the tumor. The results were compared with intraoperative findings in 12 patients and with postmortem findings in 1 patient. A tumor was demonstrated by EUS in 12 patients and was confirmed at surgery in all 12 patients. In one patient no tumor was demonstrated by EUS, although a tumor was visible by CT; no tumor was found at surgery. In two patients CT failed to demonstrate a pancreatic tumor that was demonstrated by EUS; at surgery a tumor was detected in both patients. EUS detected blood vessel involvement in seven patients, which was confirmed at surgery in six of them. In the other six patients surgery confirmed the EUS finding of no blood vessel involvement. CT detected blood vessel involvement in two patients only. The overall accuracy of EUS and CT for detecting the tumor was 100% and 77% respectively, and for blood vessel involvement 92% and 61% respectively. In conclusion, EUS is an accurate procedure for preoperative assessment of blood vessel involvement in patients with pancreatic cancer. This procedure may enable the selection of those patients who may benefit from surgery, and should be part of the evaluation of patients with pancreatic cancer who are candidates for curative surgery.

Adenocarcinoma↗

Use of anti-basement membrane antibodies to distinguish blood vessel capillaries from lymphatic capillaries.

A new method has been developed for identifying blood vessel capillaries and distinguishing them from lymphatic capillaries. Highly purified antibodies to two ubiquitous components of basement membrane--Type IV collagen and laminin--were applied to fresh-frozen and formalin-fixed tissue sections rich in blood vessel capillaries (granulation tissue), rich in lymphatic channels (small intestine and mesentery), and rich in both (skin, lung, and breast). Staining patterns were evaluated using standard immunofluorescence and immunoperoxidase techniques. Blood vessel capillaries contained intact basement membranes with linear staining for both Type IV collagen and laminin. Lymphatic capillaries, in contrast, uniformly lacked immunoreactivity with antibodies to these basement membrane components. These lymphatic capillaries, which were indistinguishable from blood vessel capillaries in both size (cross-sectional area) and shape (vessel eccentricity), were confirmed as lymphatics by dye injection studies. Our immunohistological technique detected 7-10 times more blood vessels than hematoxylin and eosin staining. Both benign and vessels than hematoxylin and eosin staining. Both benign and malignant tumors of blood vessel endothelium including two capillary hemangiomas and two angiosarcomas demonstrated extracellular linear staining for both Type IV collagen and laminin, whereas two lymphangiomas and two lymphangiectasias were negative. This method then provides a sensitive technique for detecting blood vessel capillaries in tissue sections and a reliable means of distinguishing blood vessel capillaries from lymphatic capillaries. This method may also aid in the identification of tumors whose origin is blood vessel endothelium.

Animals↗

Confocal microscopy study of nerves and blood vessels in untreated and treated port wine stains: preliminary observations.

BACKGROUND AND OBJECTIVE: Vascular ectasia in port wine stain birthmarks (PWS) might result from reduced innervation with loss of autonomic stimulation. We investigated this theory and evaluated nerve and blood vessel density, and mean blood vessel size in untreated and treated PWS skin. METHODS: Skin biopsy specimens were obtained from uninvolved skin, untreated PWS, PWS with a good response to laser treatment and PWS with a poor response to laser treatment. Confocal microscopy was performed to determine nerve and blood vessel density, and mean blood vessel size. RESULTS: Nerve density was significantly decreased in all PWS sites compared to uninvolved skin. Mean blood vessel diameter was larger in untreated compared to treated PWS. PWS with a good response to treatment had decreased nerve density but blood vessel density and mean diameter was relatively normal. PWS with a poor response to treatment had decreased nerve density but increased blood vessel density and mean blood vessel diameter compared to normal skin. CONCLUSION: Nerve density was decreased in all evaluated PWS sites and this may be a factor in lesion pathogenesis. PWS blood vessel size correlated with pulsed dye laser response and may prove to be a useful prognostic indicator of therapeutic outcome.

Adult↗

Elastin in blood vessels.

Elastin fibres give blood vessels important rheological properties, such as the postsystolic elastic recoil. The age-dependent increase of Ca2+ and lipid content, and elastolytic degradation of the fibres progressively impairs their function and produces circulating elastin peptides. Their interaction with the elastin receptor on smooth muscle cells induces not only increased cell-elastin fibre adhesion and endothelium-dependent vasorelaxation but also the release of lytic enzymes and oxygen free radicals from monocytes penetrating the vascular wall during atherogenesis. The age-dependent 'uncoupling' of the receptor has been shown to be involved in the loss of Ca2+ homeostatic mechanisms and the progressive calcification of the vessel wall.

Aging↗

[Aging changes in conjunctival blood vessels].

The relation of the changes in the conjunctival blood vessels to the age were studied in a group of 217 persons aged 20 to 79 years. All persons suffering from arterial hypertension, diabetes, systemic diseases and manifested forms of arteriosclerosis were excluded. It has been proved that examination of the conjunctival blood vessels by means of the slot-lamp facilitates the study of the changes in the microscopic blood vessels in relation to the age. Most conspicuous was the increase of the meander course of the blood vessels, also the increasing number of blood vessels is more frequent in the group of older persons. Clusters of vessels and a narrowing of the diameter of the arterioles was seen only in persons over fifty years of age. The "upright" course of the arterioles was found only in individual cases and without any special dependence to age. Sacculations on the small veins and microaneurysms on the arterioles were not observed in any of the examined group of healthy persons.

Adult↗

Injuries to major blood vessels during endoscopy.

Major blood vessel injury is a true emergency during endoscopic procedures. Too often, fear of litigation quashes the opportunity to assess the cause and learn from the experience of others. Frequently, only through a medicolegal review can such events be evaluated. A review of 47 such cases highlighted several key lessons. Proper technique for inserting the Veress needle, laparoscopic cannula, and open cannulas can prevent most accidents. If standard precautions during insertion are breached, safety shields on disposable cannula sleeves may not prevent or reduce the risk of major vessel injury. Distorted anatomy or steep Trendelenburg position may increase the risk. Retroperitoneal hematomas require exploratory laparotomy for proper assessment. Dissections around the great vessels of the pelvis require the same methods and precautions during laparoscopy as during laparotomy.

Blood Vessels↗

A comparative stereologic and ultrastructural study of blood vessels in odontogenic keratocysts and dentigerous cysts.

Blood vessels were investigated both stereologically and ultrastructurally in keratocyst and dentigerous cyst. The volume and surface densities of blood vessels in 15 keratocysts and dentigerous cysts were analyzed stereologically. No significant differences were found between them using these parameters, suggesting that their overall vascularity may be similar. However, the ultrastructural study showed marked differences between blood vessels in these two types of cysts. It was observed that fenestrated capillaries were found only in keratocysts. In addition, degeneration of endothelial lining associated with thrombosis was also a prominent feature of this cyst. While ruptured endothelium, narrow lumen and Weibel-Palade bodies were characteristic of vessels in dentigerous cyst. The presence of fenestrated capillaries in keratocyst and not in dentigerous cyst might indicate a rapid transfer of fluid to meet the demand of the relatively active proliferating epithelium, which may be promoted by growth factors released from platelets in those thrombosed vessels.

Arterioles↗