Endothelium Of Blood Capillaries Research Articles

THE INFLUENCE OF A PERIPHERAL TUMOR ON THE BEHAVIOR OF ANIMALS AND THE STRUCTURE OF NEURONS IN THE PREFRONTAL CORTEX

Melanoma is the most aggressive of the common forms of skin cancer. Proinflammatory cytokines produced by the tumor and delivered via the circulatory and lymphatic systems can lead to damage to the structures of the central nervous system. Damage to the blood-brain barrier and the endothelium of blood capillaries can cause dysfunction of neurons in the cerebral cortex, induce changes in neural plasticity, cognitive functions and result in the development of depression. Depression is observed in 20% of the cancer patients, and it affects quality of life, treatment effectiveness and survival. Depression has been linked to damage to the prefrontal cortex, which plays an important role in many brain functions, including cognition, emotion regulation, motivation and sociability.

Effect of the First Feeding on Enterocytes of Newborn Rats.

The transcytosis of lipids through enterocytes occurs through the delivery of lipid micelles to the microvilli of enterocytes, consumption of lipid derivates by the apical plasma membrane (PM) and then their delivery to the membrane of the smooth ER attached to the basolateral PM. The SER forms immature chylomicrons (iChMs) in the ER lumen. iChMs are delivered at the Golgi complex (GC) where they are subjected to additional glycosylation resulting in maturation of iChMs. ChMs are secreted into the intercellular space and delivered into the lumen of lymphatic capillaries (LCs). The overloading of enterocytes with lipids induces the formation of lipid droplets inside the lipid bilayer of the ER membranes and transcytosis becomes slower. Here, we examined components of the enterocyte-to-lymphatic barriers in newly born rats before the first feeding and after it. In contrast to adult animals, enterocytes of newborns rats exhibited apical endocytosis and a well-developed subapical endosomal tubular network. These enterocytes uptake membranes from amniotic fluid. Then these membranes are transported across the polarized GC and secreted into the intercellular space. The enterocytes did not contain COPII-coated buds on the granular ER. The endothelium of blood capillaries situated near the enterocytes contained only a few fenestrae. The LCs were similar to those in adult animals. The first feeding induced specific alterations of enterocytes, which were similar to those observed after the lipid overloading of enterocytes in adult rats. Enlarged chylomicrons were stopped at the level of the LAMP2 and Neu1 positive post-Golgi structures, secreted, fused, delivered to the interstitial space, captured by the LCs and transported to the lymph node, inducing the movement of macrophages from lymphatic follicles into its sinuses. The macrophages captured the ChMs, preventing their delivery into the blood.

Recirculation and adaptation secrete enzymes of digestive glands

The glands of the digestive tract secrete secrets, secretions and excretions into their ducts, into the cavity of organs, into the lymph and blood fl ow. A signifi cant part of the secreted hydrolytic enzymes is absorbed from the small intestine into the lymph and circulating bloodstream. The enzymes found in the blood plasma in free and adsorbed by its proteins, corpuscular elements, the endothelium of blood capillaries, inhibitors are rectifi ed by the glandulocytes of the glands into the chyme, take multiple participation in the hydrolysis of food nutrients and secretions, that is, they are recycled in the macroorganism. Hydrolases have the properties of signaling molecules, have regulatory and modulating eff ects on the processes of secretion and recreation of enzymes, on the organization of food and chyme motility adapted to the nutrient composition of food intake. In the urgent enzymatic adaptation of the secretion of the digestive glands, an essential role is played by the principle of the morphofunctional organization of the activity of the digestive secretory- transport modules. Each of them has specialized sensory, conductive aff erent and eff erent elements, and in the gland itself — specialized microregions and a system of secretion ducts with a microreservoir- valve apparatus.

On the mechanisms of damaging effect of diabetogenic chelators on the endothelium of blood capillaries in pancreatic islets

Authors showed that administration of diabetic zinc binders (DZC) to animals is accompanied not only by destruction and death of B cells, but also by the development of morphological changes in the capillaries of pancreatic islets at the site of contact with B cells (destruction of the capillary endothelium sites, change in the shape of the capillary lumen, erythrocytes adhesion, perivascular edema, hyperemia). Vascular changes are usually late complications of diabetes. To answer the question: are the described changes in islet capillaries a late complication of diabetes (1) or is it the result of the direct damaging effect of DZC (2) , low doses of DZC that do not cause diabetes in animals are used, forming a toxic zinc-dithizone complex only at B-pole cells in contact with the capillary wall. It was shown that in this case, the capillary wall is damaged in the absence of diabetes, which indicates a direct damaging effect of DZC not only on B-cells but also on the endothelium of islet capillaries. This is not a direct cause of the development of these forms of diabetes, but may be accompanied by circulatory disorders in pancreatic islets and a worsening of the course of the disease.

Age-related changes in blood capillary endothelium of human dental pulp: an ultrastructural study.

To describe the ultrastructural changes that occur in pulpal blood capillaries as a result of ageing. Thirty samples of healthy dental pulps were obtained from functional human permanent teeth. Two age groups were examined: young (10-17 years) and old (>60 years). The teeth were extracted under local anaesthesia using mepivacaine without adrenaline (Scandonest 3%, Septodont, Saint-Maur des Fossés, France) and split longitudinally in a bench press. The pulps were gently removed, immersed in fixative solution, sectioned and processed by conventional transmission electron microscopic techniques. Micrographs were taken from the endothelium, and the whole capillary area of each vessel was examined. In young pulps, the endothelial cell layer was characterized by the presence of numerous pinocytotic vesicles and microvesicles, RER cisterns, free ribosomes, a small Golgi complex, centrioles, microtubules, microfilaments and mitochondria. In the endothelial cell cytoplasm of older pulpal vessels, pinocytotic vesicles and microvesicles, as well as microfilaments, were more numerous. In addition, lipid-like vacuoles, monogranular glycogen granules and extensive Golgi complexes with dilated cisterns were also present. Weibel-Palade bodies were observed in both age groups without showing variations related with age. The results obtained in capillaries of aged pulpal tissue suggest that the endothelium experiences morphological changes that could be associated with advancing age.

Ultrastructural changes in fat cells and blood capillaries of the mammary gland in starved mice.

The effects of starvation on fat cells and blood capillaries of the first abdomino-inguinal mammary gland in mice were investigated by light and transmission electron microscopy. The body weight of starved mice abruptly decreased to approximately 70% of that of controls at 3 days of starvation and, thereafter, gradually decreased. In adipose tissues of mammary stroma, multilocular fat cells increased in number and clustered during starvation to a glandular appearance at 6 days. Collagen fibers increased in amount around mammary ducts and buds. By electron microscopy, multilocular fat cells possessed numerous mitochondria, small lipid droplets, and plasmalemmal vesicles, while endothelial cells of the blood capillaries showed numerous pinocytotic vesicles plus short marginal folds and microvillous processes. These observations prove that the number of pinocytotic vesicles in blood capillary endothelium is closely related with the increased amount of lipid of fat cells in the mammary gland during starvation.

Ultrastructural changes in endothelium of blood capillaries in canine myocardial ischemia and reperfusion injury

Ultrastructural changes in endothelium of blood capillaries in canine myocardial ischemia and reperfusion injury

Laminin, type IV collagen, and fibronectin in normal and cryptorchid human testes. An immunohistochemical study

An immunohistochemical study of laminin, type IV collagen, and fibronectin was carried out in the testes of normal men and in the cryptorchid and contralateral scrotal testes of cryptorchid men from 2 to 40 years of age. The integrated optical density (IOD) per unit area of the lamina propria was measured in the immunostained sections. Fibronectin was found throughout the thickness of the lamina propria of the seminiferous tubules and in the interstitial connective tissue. No differences between normal and cryptorchid testes were found. Laminin was observed in the innermost part of the lamina propria of the seminiferous tubules and surrounding the endothelium of blood capillaries from infancy. No differences were found between normal and cryptorchid testes in the prepubertal period. In adult cryptorchid testes, laminin formed more numerous and deeper invaginations towards the seminiferous epithelium than in normal adult testes. Type IV collagen appeared throughout the thickness of the lamina propria of normal testes as well as in the wall of interstitial blood vessels. From infancy, the lamina propria of seminiferous tubules, but not blood vessel walls, showed lesser immunostaining for type IV collagen and a lower IOD of this component than did control tests from men of the same age. No differences between unilateral and bilateral cryptorchidism were found. The contralateral scrotal testes of cryptorchid males showed intermediate immunostaining for type IV collagen between that of normal control testes and that of cryptorchid testes. These findings suggest that the lamina propria of seminiferous tubules is lesioned at an early age in both cryptorchid and contralateral scrotal testes of cryptorchid men.

Lymphoscintigraphy: Radiopharmaceutical selection and methods

Lymphoscintigraphy offers the clinician unique access to lymph nodes and lymphatics which otherwise may be unavailable for evaluation by noninvasive means. By deposition of a radioactive lymphoscintigraphic agent in a tissue whose lymphatic drainage requires definition or whose lymph nodes require evaluation, both dynamic and static functional information concerning the patency and anatomy of lymph vessels and nodes may be obtained. There is currently a broad range of radiopharmaceuticals available for lymphoscintigraphy. They fall into 3 ma.jor categories: radiocolloids, radiolabeled macromolecules, and within the macromolecule category, monoclonal antibodies for tumor detection. Uptake into lymphatic vessels is presumed to occur by a common mechanism. Radiolabeled colloids or macromolecules may either enter lymph channels through lymphatic capillaries passively or, in the case of colloids, be phagocytosed by macrophages and transported within lymphatic channels. Depending upon the size of the macromolecule, some blood capillary uptake is believed to occur from the injection site causing higher blood background levels. However, the absence of a basement membrane in lymphatic vessel endothelium permits entrance of molecules into the lymphatics which are excluded by blood capillary endothelium (Wahl et al., 1987). Colloidal particles are trapped in macrophages within the lymph nodes (Peyton, 1981). The accumulation of radiocolloid or radiolabeled macromolecules will depend upon the presence of a functionally intact node. Replacement of nodes by tumor or recent surgery in the area drained by the lymph node group may affect the ability of a lymph node to accumulate the particle or molecule. The nonspecific macromolecules (99”Tclabeled noncolloidal human serum albumin and 99mTc-labeled dextran) generally demonstrate a shorter residence time in the nodes than colloids. Some radiolabeled particles or molecules will pass beyond the draining nodes, eventually draining into the venous system, and, finally, becoming trapped in the reticuloendothelial system. From the lymphatics, access by the macromolecules is eventually gained to the venous system where blood pool activity and renal activity due to clearance through the kidneys may be seen. The selection of the lymphoscintigraphic agent depends upon the information required from the study. Historically, radiocolloids were the first lymphoscintigraphic agents used. Sage et al. (1964) and Fee et al. (1978) used [198Au]gold colloid to study lymphedema and melanoma, respectively. The radioactive gold colloid provided an ideally sized particle (2-10 nm) which permitted relatively rapid clearance from injection sites into lymphatic channels. However, the long physical half-life (2.7 d) and fl radiation emission severely limited the amount of radioactivity which could be administered. Even with the usually administered dose of 15OpCi (5.6 MBq) radiation necrosis at the injection site was reported (Osborne et al., 1983). Ultimately, gold colloid was abandoned because of the unacceptable dosimetry. 99”Tc-sulfur colloid offered an alternative. Although the physical half-life emission characteristics were more suited to human use and y camera imaging, the larger particle size (100 nm to 2 pm) meant that significant numbers of the colloid particles either failed to enter the lymphatic system or entered very slowly. Clearance from the injection site of only 30% over several hours is typical. Thus, in theory, because change in the distribution of this radiocolloid occurs more slowly, dynamic imaging should be less satisfactory with this preparation. Nonetheless, primary lymphedema as well as dermal lymphatic drainage have been explored using this radiocolloid. One alternative has been to filter 99mTc-sulfur colloid through a millipore filter (Sacks et al., 1983). This provides a smaller particle ( -=I 220 nm). %Tc--rhenium colloid provides an average sized particle of 40 nm. Although not available in the U.S., it has been used for lymphoscintigraphy in Europe. In the mid-1960s, Garzon (1965) developed a method to make *Tc-antimony trisulfide colloid. The average particle size of 12 nm is more suited to

Comparative study of lymphatics and bllod vessels.

Two methods were used to distinguish between lymphatic capillaries and blood capillaries at the light microscopic level: in one toluidine blue sections were embedded in epoxy resin following arterial perfusion-fixation, and in the other an immunohistochemical technique used basement membrane antisera (laminin, type IV collagen and fibronectin antisera) in indirect immunoperoxidase and immunogold-silver staining (IGSS) methods. The precise immunolocation of these basement membrane components around these capillaries was examined electron microscopically by pre-embedding immunoperoxidase and post-embedding immunogold techniques. The toluidine blue sections showed two types of capillaries: one with blue-stained lumens and the other with vacant lumens. Conventional electron microscopy revealed that capillaries with blue-stained lumens are lymphatic capillaries and capillaries with vacant lumens are blood capillaries by their fine structural characteristics. Immunohistochemical techniques using laminin or type IV collagen antiserum in both the immunoperoxidase and IGSS methods showed blood capillaries with continuous and linear reactions and lymphatic capillaries with absent or weak reactions beneath the endothelium. Immunostaining of fibronectin antiserum was observed nonspecifically around both types of capillaries and in connective tissue. Fine granular products in the IGSS method were in sharper contrast against the background and were more intensely stained and thinner than the DAB reaction products demonstrated by the immunoperoxidase method. Immunoelectron microscopy revealed greater immunoreactivity of laminin and type IV collagen antisera in the lamina densa around blood capillaries than in that around lymphatic capillaries. A striking feature was the presence of fibronectin antiserum in the intracellular organelles of blood capillary endothelium and on the surface of fibroblasts. In conclusion, toluidine blue staining following arterial perfusion-fixation is a useful technique for experimental pathologists, and the IGSS method using laminin and type IV collagen antisera is a practical light microscopic method of distinguishing between lymphatic capillaries and blood capillaries.

Distribution of cell surface charges on mesothelium and lymphatic endothelium

The distribution of anionic sites on the luminal surfaces of the peritoneal mesothelium and lymphatic endothelium was investigated by injecting cationized ferritin (CF) intraperitoneally. After washing with phosphate-buffered saline, the diaphragm was fixed and processed for electron microscopy. CF label occurred in discontinuous patches along the mesothelial surface. Microvilli were heavily marked and often closely applied to the mesothelial surface. The intercellular cleft was also heavily labeled. The luminal aspect of the lymphatic endothelium was more extensively labeled, with the marker occurring in long discontinuous dense bands. The clefts of lymphatic endothelial intercellular junctions were extensively labeled especially along regions where cells were loosely apposed. The existence of a high density of anionic sites on membranes at the intercellular junctions of both mesothelial and lymphatic endothelial cells represent a salient feature which is very different from binding in blood capillary endothelium. The presence of a high density of anionic sites along the intercellular clefts of adjacent cells may play a role in the rapid movement of small solutes and molecules from interstitial spaces into the lymphatic lumen.

Transendothelial channels in fenestrated endometrial blood capillaries of rats

Three types of transendothelial channels are described in the endothelium of blood capillaries in the endometrium of the rat. It is postulated that they may function as pores draining interstitial fluid to the venous blood.

Increase in the rough endoplasmic reticulum in capillary endothelial cells and pericytes in hyperplastic rat thyroid glands.

Observatios were made on the rough endoplasmic reticulum (RER) of the blood capillary endothelium, pericytes, and lymphatic endothelium in the course of studies of changes occurring in the thryoid gland during the development of thyroid hyperplasia. To induce the hyperplasia, Fischer rats were fed a goitrogen (thiouracil) an a low iodine diet for various time intervals from 3-100 days. Thyroid glands were fixed by perfusion with glutaryldehyde and embedded in Epon. A noticeable increase in the RER in the capillary endothelium was seen by 3 days. This increase was very pronounced by 7 days and persisted in many cells at 100 days. The RER response was also pronounced in pericytes. In the lymphatic endothelium, however, the increase in RER was barely perceptible. These results suggest that capillary endothelium and pericytes have protein synthetic and secretory functions of an unknown nature that become strongly activated in stimulated thyroid glands.

The passage of macromolecules across inflamed capillary endothelium via large vacuoles

It was found that ferritin molecules are transported across inflamed blood capillary endothelium in large vacuoles as well as in small vesicles. Ferritin could be seen leaving such organelles, attached to the ablumenal plasma membranes, 30 to 60 sec after it had been injected into the blood, and well before there was any buildup of the tracer in the tissues adjacent to the endothelium.

Quantitative ultrastructural morphometry of blood capillary endothelium in skeletal muscle: Effect of venous pressure

Rat hindquarter preparations were perfused with a plasma substitute for 20 min at high venous pressure (+10 cm H 2O; HVP rats) or low venous pressure (−4 cm H 2O; LVP rats). Perfusion-fixed specimens for electron microscopy were obtained from the rectus femoris, biceps femoris, tibialis anterior, and gastrocnemius (medial head) muscles. Endothelial thickness and frequency of plasmalemmal vesicles (luminal, abluminal, and free vesicles) were assessed on randomly selected capillaries. Mean endothelial thickness was: HVP, 0.26 μm; LVP, 0.28 μm ( P < 0.02). In both groups the abluminal vesicles outnumbered the luminal ones ( P < 0.01), by 35% (LVP) and by 8% (HVP). This difference in abluminal vesicle excess was significant ( P < 0.01). There were no statistically demonstrable differences between the groups in luminal or free vesicle counts per unit luminal surface area or in total vesicle count per unit cytoplasmic volume. The depletion of abluminal vesicles in HVP rats conformed quantitatively with a concept of vesicle membrane incorporation into the plasmalemma proper at pressure-induced capillary dilatation. Provided that the vesicular turnover rate does not change with pressure, the net effect of the reduction in size of the abluminal vesicle population could be an augmented vesicle-bound transendothelial transport of macromolecules from the capillaries to the interstitium. The study indicates that vesicular transport should be regarded as a balance, influenced by hemodynamics, between two separate transport processes in the respective directions.

The dimensions and numbers of small vesicles in blood capillary endothelium in the hind legs of dogs, and their relation to vascular permeability.

SUMMARYThe dimensions and numbers of vesicles were determined in the blood capillary endothelium of the gastrocnemii muscle of dogs. These results permitted more accurate calculations of the number of vesicles crossing the endothelium in one direction/sec/(μm2 (∼6·2), and of the median vesicular attachment time (∼8 sec). The probability of fusion occurring when a vesicle contacts a plasma membrane (α= 0·004) was unchanged: hence it was concluded, from the mean cellular width (0·21 μm) and the calculated cytoplasmic viscosity (∼0·1 poise), that ∼49% of the vesicles starting from one side reached the other one, and that their median transit time was ∼1 sec.

Transport of large molecules from plasma to interstitial fluid and lymph in dogs.

Transport of large molecules from plasma to interstitial fluid and lymph in dogs.

The dimensions and numbers of small vesicles in cells, endothelial and mesothelial and the significance of these for endothelial permeability.

SUMMARYMeasurements were made of the diameters, numbers and other parameters of small, smooth‐surfaced vesicles in the endothelium of blood capillaries and lymphatics, and in the mesothelial cells of the diaphragms of mice. Some measurements were also made on the aortic endothelium. With a few exceptions, there were no morphological differences between the various sites.It was found that between 25% and 35% of the non‐nuclear cell volume was composed of vesicles, whose membranes accounted for about 55% of their volumes. Their internal volumes were ∼ 70,000 nm3, totalling ∼ 0·04 μm3/μm2 of luminal surface area. For each 1 μm2 there were ∼ 135 vesicles attached to each surface membrane of the cell, and between ∼ 200 and ∼ 350 vesicles lying free in the cytoplasm. There was probably a slight amount of shrinkage during the preparation of the material, and the true linear dimensions were probably ∼ 105% of those actually observed. Thus the values for the internal volumes were probably ∼ 85,000 nm3 and ∼005 μm3 respectively; the vesicular numbers were probably ∼ 125 attached to each surface and between ∼ 175 and ∼ 300 free.The vesicles attached to the plasma membranes often had quite long stalks; these were estimated to be ∼ 30 nm at the moment of rupture. Thus the vesicles must be released an appreciable distance away from the membrane. This modifies the conclusions of Shea &amp; Karnovsky (1966), since it can now be shown that Brownian movement alone is capable of accounting for the release of the vesicles, their movements within the cells and their transportation of material.By combining these results with others estimating the endothelial permeability coefficients, it can be calculated that the average free lifetime of a vesicle is ∼1½ sec, from union with one plasma membrane to the next. It can also be shown that the average time of such an attachment is ∼ 2½ sec. There are many possible sources of error relating to these measurements; they must only be regarded as tentative. It appears likely, however, that they are of about the correct order of magnitude as they accord well with other data.