Walls Of Blood Capillaries Research Articles

Pulsatile flow of biviscous fluid through a tube of varying cross-section

In this paper, a pulsatile flow of a biviscous fluid in a circular tube of varying cross-section has been considered for investigation. The study helps to draw the characteristics of blood, the pressure drop and the wall shear stress on the inner wall of small blood vessels and capillaries where suction/injection velocity arises and Reynolds number is very low. The effects of Reynolds number, apparent viscosity coefficient and leakage parameter on the streamlines, pressure drop and wall shear stress have been discussed and shown graphically for suction and injection, respectively. The wall of the tube is supposed to be permeable and a normal velocity of the fluid at the wall is prescribed to consider the fluid exchange across the wall. Both analytic and numerical solutions are given. Using the perturbation technique, we analyze the problem for low Reynolds numbers and small oscillation amplitude. Lastly, the simulations are given to demonstrate the effectiveness and excellent tracking performance of the proposed control scheme.

SUBMICROSCOPIC CHANGES IN HEMOCAPILLARIES OF ADRENAL GLAND AND PANCREATIC ISLETS OF LANGERHANS IN CASES OF IMMOBILIZATION STRESS WITH UNDERLYING HYPOTHYROIDISM

Background. Today, among the increasing number of various diseases, stress is a trigger in the development of diseases and mortality among the population. Objective. To establish submicroscopic changes in the hemocapillaries of the islets of Langerhans of the pancreas and adrenal glands in the presence of immobilization stress with underlying hypothyroidism. Methods. The experiment was carried out on 20 mature white male rats. Hypothyroidism was modeled by daily per os injection with a probe of the pharmacopoeial mercazole thyreostatics at a dose of 25 mg/kg for 21 days. Acute immobilization stress was modeled by tying the experimental rats in a supine position in 4 limbs without restricting head mobility for 3 hours. The study was conducted 2 hours later (anxiety stage) after the end of the stress impact. The material was collected for electron microscopy and tissue processing was performed according to generally accepted methods. Results. Electron microscopic examination of the blood capillaries of the islets of Langerhans in the pancreas and the hemocapillaries of the adrenal cortex after the action of the stress factor in cases of hypothyroidism showed slightly enlarged lumens and moderate perivascular edema. The basement membrane was moderately thickened but clearly contoured. Endotheliocyte nuclei were mostly hypertrophied, euchromatin was uniformly located in the nucleoplasm, and nucleoli were defined. The karyolemma was clearly contoured, the number of nuclear pores was small, and the perinuclear lumen was locally widened. Endoplasmic reticulum with moderately expanded and short tubules, moderately thickened cisterns of the Golgi complex were observed in the cytoplasm of endotheliocytes. There were two types of mitochondria: hypertrophied with an electron-light matrix, single cristae, and with clear visible cristae and a moderately electron-dense matrix. In addition to the capillaries mentioned above, there were also single narrowed microvessels that had perivascular edema and vaguely contoured fenestrae. Conclusions. When modeling a stressor in cases of hypothyroidism, structural changes of all components of the walls of blood capillaries of the pancreas and adrenal glands take place.

Vascular permeability in patients with portal hypertension before and after surgery

The issue of the passage of protein substances through the walls of blood capillaries is controversial.

Manufacturing a Bone Marrow-On-A-Chip Using Maskless Photolithography.

The bone marrow (BM) is a complex microenvironment in which hematopoietic stem and progenitor cells (HSPCs) interact with multiple cell types that regulate their quiescence, growth, and differentiation. These cells constitute local niches where HSPCs are confined and subjected to specific set of physical and biochemical cues. Endothelial cells forming the walls of blood capillaries have been shown to establish a vascular niche, whereas osteoblasts lying along the bone matrix organize the endosteal niche with distinct and specific impact on HSPC fate. The observation of the interaction of HSPCs with niche cells, and the investigation of its impact on HSPCs behavior in vivo is hindered by the opacity of the bone matrix. Therefore, various experimental strategies have been devised to reconstitute in vitro the interaction of HSPCs with distinct sets of BM-derived cells. In this chapter, we present a method to manufacture a pseudo BM-on-a-chip with separated compartments mimicking the vascular and the endosteal niches. Such a configuration with connected but distant compartments allowed the investigation of the specific contribution of each niche to the regulation of HSPC behavior. We describe the microfabrication of the chip with a maskless photolithography method that allows the iterative improvement of the geometric design of the chip in order to optimize the adaptation of the multicellular architecture to the specific aim of the study. We also describe the loading and culture of the various cell types in each compartment.

Seasonal effect in expression of AQP1, AQP3 and AQP5 in skin of Murrah buffaloes.

Aquaporins are transmembrane protein channels which are known to help the passage of water and solutes across the cell membranes. AQP1, AQP3 and AQP5 are isoforms of aquaporin known to aid in transepithelial water movement. AQP3 is also known to aid in glycerol transport. The present study was conducted to investigate the role of AQP1, AQP3 and AQP5 in thermoregulation of buffaloes by probing the expression of the genes in skin of buffaloes during different season viz. winter, spring and summer. The skin tissue samples were collected from the neck region of Murrah buffaloes (n=12) and analyzed for gene expression by RT-PCR and immunolocalization. The physiological responses including respiration rate, rectal temperature and neck skin temperature observed during summer were significantly higher than winter and spring seasons. The study revealed the expression of AQP1, AQP3 and AQP5 genes in skin samples. The relative mRNA expressions of AQP1, AQP3 and AQP5 in skin relative to spring season were 1.41±0.47, 1.95±0.22 and 6.77±1.02 folds during summer which were significantly higher than other seasons. The up-regulation of the expression of the studied AQPs were concomitant with the increase in physiological responses including skin temperature and sweating rate during summer. During summer season, AQP1 were mostly immunolocalized in the walls of skin blood capillaries, while AQP3 were observed mostly in the epidermal layer of the skin. The immunolocalization of AQP5 were mostly observed in the secretory glands of skin. The up-regulation of AQP1, AQP3 and AQP5 in skin during summer season indicates their role in thermoregulation of buffaloes.

The possible alleviating effect of saffron on chlorpyrifos experimentally induced cardiotoxicity: Histological, immunohistochemical and biochemical study

IntroductionPesticides are responsible for many occupational health hazards among farmers in developing countries. Chlorpyrifos (CPF) is one of the broad-spectrum organophosphorus (OP) insecticides used for agricultural, domestic and industrial purposes. Aim of the workThe present study was designed to examine the effects of CPF on cardiac muscles and to evaluate the possible protective role of crocin using biochemical and histological methods with the intention to recognize the molecular tools of its probable cardioprotective effects. Materials and methodsThirty-six adult male albino rats were used in this study and were divided into 4 equal groups (9 rats each): negative control group, positive control group, CPF treated group and CPF & crocin treated group. The heart was removed for histological and immunohistochemical studies. ResultsStained sections of cardiac muscle fibers of group III with H&E revealed remarkable histological changes in the form of disorganization of the fibers with increase in the interstitial spaces between these fibers. Congested dilated blood capillaries could be observed with extravasation of the red blood cells leading to interstitial hemorrhage. Focal areas of mononuclear cellular infiltration could be seen in the interstitial tissue. A number of cardiac fibers achieved pale acidophilic vacuolated sarcoplasm while others achieved dark homogenous acidophilic sarcoplasm. Some nuclei were peripherally situated and pyknotic while others were centrally situated and encircled with halos. Apparently increased masses of collagen fibers among the cardiac muscle fibers and around the congested dilated blood vessels with the presence of focal parts of extensive collagen fiber deposition were noticed in Mallory-stained sections of group III. Strong positive immunoreactions in the endomysium and perimysium of the cardiac fibers, along with the walls of blood capillaries and in interstitial cells, could be detected in immunohistochemical staining sections of group III with vimentin antibody. Immunoreactivity to caspase 3 was higher in the sarcoplasm of the cardiac fibers of group III compared to that of control group. A highly significant decrease in the cardiac level of SOD and CAT; however, a highly significant increase in MDA level was noted between the control groups and CPF treated group.Additionally, there was a significant improvement of the chemical and histological representations of group IV, and these improvement pictures were toward the normal. ConclusionThe study concludes that crocin can alleviate the toxic effect of chlorpyrifos caused by oxidative stress on cardiac muscle.

Predicting different adhesive regimens of circulating particles at blood capillary walls

A fundamental step in the rational design of vascular targeted particles is the firm adhesion at the blood vessel walls. Here, a combined lattice Boltzmann–immersed boundary model is presented for predicting the near-wall dynamics of circulating particles. A moving least squares algorithm is used to reconstruct the forcing term accounting for the immersed particle, whereas ligand-receptor binding at the particle–wall interface is described via forward and reverse probability distributions. First, it is demonstrated that the model predicts with good accuracy the rolling velocity of tumor cells over an endothelial layer in a microfluidic channel. Then, particle–wall interactions are systematically analyzed in terms of particle geometries (circular, elliptical with aspect ratios 2 and 3), surface ligand densities (0.3, 0.5, 0.7 and 0.9), ligand-receptor bond strengths (1 and 2) and Reynolds numbers (Re = 0.01, 0.1 and 1.0). Depending on these conditions, four different particle–wall interaction regimens are identified, namely not adhering, rolling, sliding and firmly adhering particles. The proposed computational strategy can be efficiently used for predicting the near-wall dynamics of particles with arbitrary geometries and surface properties and represents a fundamental tool in the rational design of particles for the specific delivery of therapeutic and imaging agents.

Distinctive actions of connexin 46 and connexin 50 in anterior pituitary folliculostellate cells.

Folliculostellate cell gap junctions establish a network for the transmission of information within the anterior pituitary. Connexins make up gap junction channels. Changes in connexin (Cx) turnover modify gap junction-mediated intercellular communication. We have reported that cytokines and hormones influence Cx43 turnover and coupling in folliculostellate cells and in the folliculostellate cell line TtT/GF. In addition, the expression of different connexins alters intercellular communication and connexins may have functions besides cell coupling. Here we assessed the expression, turnover and subcellular localization of Cx46 and Cx50 in the anterior pituitary and TtT/GF cells. Then, we assessed the impact of various natural (lactation, annual reproductive cycle, bFGF) and pathological (autoimmune orchitis, diabetes/obesity) conditions associated with altered anterior pituitary hormone secretion on Cx46 and Cx50. Anterior pituitary Cx46 and Cx50 expression and subcellular distribution were cell-dependent. Cx46 was expressed by folliculostellate, TtT/GF and endocrine cells. In the cytoplasm, Cx46 was chiefly associated with lysosomes. Variously sized Cx46 molecules were recovered exclusively in the TtT/GF cell nuclear fraction. In the nucleus, Cx46 co-localized with Nopp-140, a nucleolar factor involved in rRNA processing. Neither cytoplasmic nor nuclear Cx46 and Cx43 co-localized. Cx50 localized to folliculostellate and TtT/GF cells, and to the walls of blood capillaries, not to endocrine cells. Cx50 was cytoplasmic and associated with the cell membrane, not nuclear. Cx50 did not co-localize with Cx46 but it co-localized in the cytoplasm and co-immunoprecipitated with Cx43. Cx46 and Cx50 responses to various physiological and pathological challenges were different, often opposite. Cx46 and Cx43 expression and phosphorylation profiles differed in the anterior pituitary, whereas Cx50 and Cx43 were similar. The data suggest that Cx46 participates to cellular growth and proliferation and that Cx50, together with Cx43, contributes to folliculostellate cell coupling.

Neurovascular coupling during cortical spreading depolarization and -depression.

Cortical spreading depolarizations (CSDs) are self-propagating waves of transient loss of neuronal transmembrane ion gradients, followed by prolonged suppression of neuronal activity (spreading depression). CSDs emerge spontaneously in animal models of traumatic brain injury,1 subarachnoid hemorrhage,2 and in focal ischemia3 where they are associated with infarct growth.4 In humans, CSDs have been demonstrated in traumatic brain injury,5 subarachnoid hemorrhage,6,7 and malignant hemispheric stroke,8 and they are believed to be the brain mechanism underlying migraine aura.9 CSDs are associated with dramatic changes in cerebral blood flow (CBF). During the depolarization phase of CSDs induced in healthy and well-perfused brain tissue in animal models, an early hyperemic response is observed, typically followed by prolonged oligemia after the neuronal repolarization. Despite the initial CBF increase, tissue hypoxia may develop in more distant territories of capillary supply.10,11 Similar CBF changes have been observed in patients with migraine aura.12–14 In the injured brain, CSDs can be accompanied by severe initial CBF reduction instead of a CBF increase during the depolarization phase, termed spreading ischemia.15 When this inverse hemodynamic response is observed, the energy-dependent recovery from CSD is delayed in a characteristic fashion, indicating a severe mismatch between oxygen supply and demand2 and a high risk of tissue damage.16 In rat and cat models of focal ischemia, CSD-related CBF transients range from monophasic, positive CBF responses in peri-ischemic tissue, over biphasic transients in mildly ischemic tissue, to negative CBF transients in more severe ischemia.17–19 During CSD in animal models, capillary flow patterns become severely disturbed.10,20,21 The passage of a CSD causes erythrocytes in some capillaries to reduce their speed, whereas other capillaries reveal 4-fold increases in flow or higher. …

Ultrasound-mediated local drug and gene delivery using nanocarriers.

With the development of nanotechnology, nanocarriers have been increasingly used for curative drug/gene delivery. Various nanocarriers are being introduced and assessed, such as polymer nanoparticles, liposomes, and micelles. As a novel theranostic system, nanocarriers hold great promise for ultrasound molecular imaging, targeted drug/gene delivery, and therapy. Nanocarriers, with the properties of smaller particle size, and long circulation time, would be advantageous in diagnostic and therapeutic applications. Nanocarriers can pass through blood capillary walls and cell membrane walls to deliver drugs. The mechanisms of interaction between ultrasound and nanocarriers are not clearly understood, which may be related to cavitation, mechanical effects, thermal effects, and so forth. These effects may induce transient membrane permeabilization (sonoporation) on a single cell level, cell death, and disruption of tissue structure, ensuring noninvasive, targeted, and efficient drug/gene delivery and therapy. The system has been used in various tissues and organs (in vitro or in vivo), including tumor tissues, kidney, cardiac, skeletal muscle, and vascular smooth muscle. In this review, we explore the research progress and application of ultrasound-mediated local drug/gene delivery with nanocarriers.

Histological and Immunohistochemical Study on Human Placental Tissue in Normal Pregnancy and Preeclampsia

Background: Preeclampsia is a serious disorder affecting the mother. It may be responsible for more than 50,000 maternal deaths worldwide each year. It is a major killer of both mother and fetus. Aim: To demonstrate the morphological changes of human placental tissue in pre-eclamptic pregnancies compared with the normal by using histological and immunohistochemical techniques. Materials & Methods: Twenty pregnant women were included in this study. 10 of them were diagnosed as having moderate pre-eclampsia and considered as the pre-eclamptic (PE) group, while 10 women were clinically normal and considered as the control group. Placental specimens were obtained after either vaginal delivery or caesarian section and processed for H&E and Masson's trichrome stains, as well as for immunohistochemical stains for eNOS and HIF-1α. Morphometric measurement of number of syncytial knots, area % of collagen fibers, eNOS and HIF-1α.were done followed by statistical analysis. Results: PE group revealed thickened wall of fetal blood capillaries, crowded degenerating villi with decreased intervillous spaces, intravillous and perivillous fibrinoid deposition. Numerous syncytial knots and exfoliated trophoblast cells were also observed. There was thickened layer of subchorionic fibrinoid. Increased area% of collagen fibers, HIF-1α. immunoreactivity and decreased area% of eNOS immunoexpression were found. Conclusions: As evidenced by the previous results, this study concluded various placental changes detected by histological and histochemical techniques. The findings have clarified a significant correlation between eNOS and HIF-1α immunoexpression and pre-eclampsia. Whether this relation is causal or effect relationship, this may need further investigations for better management and avoidance of consequences of pre-eclampsia.

Reassessing cerebrospinal fluid (CSF) hydrodynamics: A literature review presenting a novel hypothesis for CSF physiology

The traditional model of cerebrospinal fluid (CSF) hydrodynamics is being increasingly challenged in view of recent scientific evidences. The established model presumes that CSF is primarily produced in the choroid plexuses (CP), then flows from the ventricles to the subarachnoid spaces, and is mainly reabsorbed into arachnoid villi (AV). This model is seemingly based on faulty research and misinterpretations. This literature review presents numerous evidence for a new hypothesis of CSF physiology, namely, CSF is produced and reabsorbed throughout the entire CSF-Interstitial fluid (IF) functional unit. IF and CSF are mainly formed and reabsorbed across the walls of CNS blood capillaries. CP, AV and lymphatics become minor sites for CSF hydrodynamics. The lymphatics may play a more significant role in CSF absorption when CSF-IF pressure increases. The consequences of this complete reformulation of CSF hydrodynamics may influence applications in research, publications, including osteopathic manual treatments.

Study of Stress Induced Failure of the Blood-gas Barrier and the Epithelial-epithelial Cells Connections of the Lung of the Domestic Fowl, Gallus gallus Variant Domesticus after Vascular Perfusion.

Complete blood-gas barrier breaks (BGBBs) and epithelial-epithelial cells connections breaks (E-ECCBs) were enumerated in the lungs of free range chickens, Gallus gallus variant domesticus after vascular perfusion at different pressures. The E-ECCBs surpassed the BGBBs by a factor of ~2. This showed that the former parts of the gas exchange tissue were structurally weaker or more vulnerable to failure than the latter. The differences in the numbers of BGBBs and E-ECCBs in the different regions of the lung supplied with blood by the 4 main branches of the pulmonary artery (PA) corresponded with the diameters of the blood vessels, the angles at which they bifurcated from the PA, and the positions along the PA where they branched off. Most of the BGBBs and the E-ECCBs occurred in the regions supplied by the accessory- and the caudomedial branches: the former is the narrowest branch and the first blood vessel to separate from the PA while the latter is the most direct extension of the PA and is the widest. The E-ECCBs appeared to separate and fail from tensing of the blood capillary walls, as the perfusion- and intramural pressures increased. Compared to the mammalian lungs on which data are available, i.e., those of the rabbit, the dog, and the horse, the blood-gas barrier of the lung of free range chickens appears to be substantially stronger for its thinness.

Osmium impregnation detection of pulmonary intravascular fat in sudden death: A study of 65 cases

Pulmonary fat embolism is widely recognised in forensic pathology. Pulmonary fat embolism requires mobilisation of free fat, entry of free fat into the circulation and lodging of fat globules in fine venous capillaries. This paradigm of fat embolisation has been used to support the evidence of antemortem fat depot disruption when the presence of intravascular fat is confirmed at autopsy. However, sporadic reports of intravascular fat in various medical conditions, which contradict the above mechanism, have opened questions about the alternative pathogenesis. In this study, 65 cases of sudden deaths were examined for the presence of pulmonary intravascular fat (PIF) by osmium impregnation. Cases were selected based on the criteria that were designed to eliminate the possible confounding effect from medical intervention or postmortem changes. Slides were graded based on their ease of search and only the fat droplets confined by the blood vessel or capillary wall were considered as a positive finding. The results show surprisingly high PIF incidences of varying degrees in all the categories of sudden deaths. Further study is needed to devise criteria for diagnosis of fatal fat embolism since the histological appearance of the high-grade PIF in natural sudden death may not be easily distinguishable from the traumatic fat embolism.

C224 肺内のガス交換に関する工学的研究(OS-13: 生体熱工学)

Numerical calculations were carried out to reveal both velocity and oxygen concentration fields around a red blood cell. It is well-known that the cell changes its shape and orientation, as it flows in a capillary. The mass and momentum conservation equations for the blood plasma were solved along with the oxygen transport equation. The effects of the shape of the red blood cell on the velocity and oxygen concentration fields are numerically investigated using a numerical model consisting of the blood plasma, red cell and capillary wall.

On the Future Development of Optimally-Sized Lipid-Insoluble Systemic Therapies for CNS Solid Tumors and Other Neuropathologies

It remains a challenge to deliver effective concentrations of therapeutics into CNS pathologies, which is primarily due to the fact that current and investigational CNS therapeutics are suboptimally-sized to accumulate to effective concentrations in individual diseased CNS tissue cells. The blood-CNS barrier of blood capillary microvasculature within neuropathologic tissues is known to be permeable to lipid-insoluble macromolecules in a wide-spectrum of neuropathologies. In the case of CNS solid tumor tissue blood capillaries, the physiological upper limit of pore size to the transcapillary passage of spherical lipid-insoluble macromolecules is approximately 12 nanometers, and systemically administered imageable dendrimer nanoparticles within the 7 to 10 nanometer size range accumulate to therapeutic concentrations in solid tumors since this size range of particles maintain peak blood concentrations for several hours. In preliminary pre-clinical studies, it has recently been shown that one intravenous dose of small molecule chemotherapy-conjugated imageable dendrimer nanoparticles within the 7 to 10 nanometer size range, with doxorubicin bound to the particle exterior via acid-labile covalent linkages, is effective at regressing orthotopic rodent malignant gliomas. Although it is foreseeable that such drug-conjugated imageable nanoparticles within the 7 to 10 nanometer size range will be effective theranostic agents for the concurrent treatment (i.e. neutron capture therapy) and imaging (i.e. magnetic resonance) of solid tumor disease, the issue of maintaining a neutralized particle exterior following the attachment of cationic drugs will need to be addressed to eliminate cationic charge-mediated nanoparticle toxicity to blood capillary walls. In this review, the ultrastructural basis for blood capillary microvascular permeability to lipid-insoluble macromolecules is discussed, and the importance of delineating the precise physiologic upper limits of pore size in the blood capillary microvasculature of other CNS pathologies, including neurodegenerative, inflammatory and ischemic CNS diseases, is emphasized. The discussion herein will serve as guide for the future development of optimally-sized, non-toxic and non-immunogenic lipid-insoluble systemic therapies, which should be the focus of future patent applications and patents on CNS drug development.

MULTISCALE MODELING OF FLUID AND SOLUTE TRANSPORT IN SOFT TISSUES AND MICROVESSELS

This study focuses on the movement of particles and extracellular fluid in soft tissues and microvessels. It analyzes modeling applications in biological and physiological fluids at a range of different length scales: from between a few tens to several hundred nanometers, on the endothelial glycocalyx and its effects on interactions between blood and the vessel wall; to a few micrometers, on movement of blood cells in capillaries and transcapillary exchange; to a few millimetres and centimetres, on extracellular matrix deformation and interstitial fluid movement in soft tissues. Interactions between blood cells and capillary wall are discussed when the sizes of the two are of the same order of magnitude, with the glycocalyx on the endothelial and red cell membranes being considered. Exchange of fluid, solutes, and gases by microvessels are highlighted when capillaries have counter-current arrangements. This anatomical feature exists in a number of tissues and is the key in the renal medulla on the urinary concentrating mechanism. The paper also addresses an important phenomenon on the transport of macromolecules. Concentration polarization of hyaluronan on the synovial lining of joint cavities is presented to demonstrate how the mechanism works in principle and how model predictions agree to experimental observations quantitatively.

Physiologic upper limits of pore size of different blood capillary types and another perspective on the dual pore theory of microvascular permeability.

BackgroundMuch of our current understanding of microvascular permeability is based on the findings of classic experimental studies of blood capillary permeability to various-sized lipid-insoluble endogenous and non-endogenous macromolecules. According to the classic small pore theory of microvascular permeability, which was formulated on the basis of the findings of studies on the transcapillary flow rates of various-sized systemically or regionally perfused endogenous macromolecules, transcapillary exchange across the capillary wall takes place through a single population of small pores that are approximately 6 nm in diameter; whereas, according to the dual pore theory of microvascular permeability, which was formulated on the basis of the findings of studies on the accumulation of various-sized systemically or regionally perfused non-endogenous macromolecules in the locoregional tissue lymphatic drainages, transcapillary exchange across the capillary wall also takes place through a separate population of large pores, or capillary leaks, that are between 24 and 60 nm in diameter. The classification of blood capillary types on the basis of differences in the physiologic upper limits of pore size to transvascular flow highlights the differences in the transcapillary exchange routes for the transvascular transport of endogenous and non-endogenous macromolecules across the capillary walls of different blood capillary types.MethodsThe findings and published data of studies on capillary wall ultrastructure and capillary microvascular permeability to lipid-insoluble endogenous and non-endogenous molecules from the 1950s to date were reviewed. In this study, the blood capillary types in different tissues and organs were classified on the basis of the physiologic upper limits of pore size to the transvascular flow of lipid-insoluble molecules. Blood capillaries were classified as non-sinusoidal or sinusoidal on the basis of capillary wall basement membrane layer continuity or lack thereof. Non-sinusoidal blood capillaries were further sub-classified as non-fenestrated or fenestrated based on the absence or presence of endothelial cells with fenestrations. The sinusoidal blood capillaries of the liver, myeloid (red) bone marrow, and spleen were sub-classified as reticuloendothelial or non-reticuloendothelial based on the phago-endocytic capacity of the endothelial cells.ResultsThe physiologic upper limit of pore size for transvascular flow across capillary walls of non-sinusoidal non-fenestrated blood capillaries is less than 1 nm for those with interendothelial cell clefts lined with zona occludens junctions (i.e. brain and spinal cord), and approximately 5 nm for those with clefts lined with macula occludens junctions (i.e. skeletal muscle). The physiologic upper limit of pore size for transvascular flow across the capillary walls of non-sinusoidal fenestrated blood capillaries with diaphragmed fenestrae ranges between 6 and 12 nm (i.e. exocrine and endocrine glands); whereas, the physiologic upper limit of pore size for transvascular flow across the capillary walls of non-sinusoidal fenestrated capillaries with open 'non-diaphragmed' fenestrae is approximately 15 nm (kidney glomerulus). In the case of the sinusoidal reticuloendothelial blood capillaries of myeloid bone marrow, the transvascular transport of non-endogenous macromolecules larger than 5 nm into the bone marrow interstitial space takes place via reticuloendothelial cell-mediated phago-endocytosis and transvascular release, which is the case for systemic bone marrow imaging agents as large as 60 nm in diameter.ConclusionsThe physiologic upper limit of pore size in the capillary walls of most non-sinusoidal blood capillaries to the transcapillary passage of lipid-insoluble endogenous and non-endogenous macromolecules ranges between 5 and 12 nm. Therefore, macromolecules larger than the physiologic upper limits of pore size in the non-sinusoidal blood capillary types generally do not accumulate within the respective tissue interstitial spaces and their lymphatic drainages. In the case of reticuloendothelial sinusoidal blood capillaries of myeloid bone marrow, however, non-endogenous macromolecules as large as 60 nm in diameter can distribute into the bone marrow interstitial space via the phago-endocytic route, and then subsequently accumulate in the locoregional lymphatic drainages of tissues following absorption into the lymphatic drainage of periosteal fibrous tissues, which is the lymphatic drainage of myeloid bone marrow. When the ultrastructural basis for transcapillary exchange across the capillary walls of different capillary types is viewed in this light, it becomes evident that the physiologic evidence for the existence of aqueous large pores ranging between 24 and 60 nm in diameter in the capillary walls of blood capillaries, is circumstantial, at best.

A computational model relating changes in cerebral blood volume to synaptic activity in neurons

Brain imaging methods, and in particular fMRI (functional Magnetic Resonance Imaging), do not detect neural activity directly, but rather changes in blood flow and oxygenation in neighboring blood vessels, this being the BOLD (Blood Oxygenation Level Dependent) effect. We have constructed a model of the steps leading from neural activity to increased blood flow in arterioles, in which astrocytes play a crucial role. Glutamate released from neuronal synapses binds to metabotropic receptors on the astrocyte processes that ensheath these synapses. This initiates a calcium wave that travels along the endfeet of astrocytes that abut the endothelial cells forming the walls of blood capillaries; this calcium wave is propagated by the extracellular diffusion of ATP (adenosine triphosphate) that acts on metabotropic purinergic receptors on the astrocytes. A further second messenger (taken to be nitric oxide) relays this signal to the smooth muscle cells forming the outer walls of arterioles, and the subsequent wave of hyperpolarization reduces calcium influx and allows relaxation of the muscle cells and hence increased blood flow. The model gives results that are in agreement with experimental measurements of blood volume changes in the arterioles in the visual cortex of optically stimulated cats.

Modeling fibrin aggregation in blood flow with discrete-particles.

Excessive clotting can cause bleeding over a vast capillary area. We study the mesoscopic dynamics of clotting by using the fluid particle model. We assume that the plasma consists of fluid particles containing fibrin monomers, while the red blood cells and capillary walls are modeled with elastic mesh of "solid" particles. The fluid particles interact with each other with a short-ranged, repulsive dissipative force. The particles containing fibrin monomers have a dual character. The polymerization of fibrin monomers into hydrated fibrins is modeled by the change of the interactions between fluid particles from repulsive to attractive forces. This process occurs with a probability being an increasing function of the local density. We study the blood flow in microscopic capillary vessels about 100 microm long and with diameters in order of 10 microm. We show that the model of polymerization reflects clearly the role played by fibrins in clotting. Due to the density fluctuations caused the by the high acceleration, the fibrin chains are produced within a very short time (0.5 ms). Fibrin aggregation modifies the rheological properties of blood, slows down the incipient flow, and entraps the red blood cells, thus forming dangerous clots.