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PubMed1981

Vascular permeability and transvascular fluid and protein transport in the dog lung.

We used steady state lymph-to-plasma concentration ratios of six endogenous protein fractions (effective hydrodynamic radii of 37, 40, 44, 53, 100, and 120 A) to estimate pulmonary capillary permeability characteristics. Pulmonary lymph was collected from an afferent lymphatic to the left tracheobronchial lymph node, and left atrial pressure was elevated in steps until the lymphatic protein concentration obtained a constant value. Lymph flow and transvascular protein flux increased with each increase in left atrial pressure. Convective flux was the predominant mode of transport for the smaller fractions, and solvent-drag reflection coefficients increased as lymph flow increased. This dependency on lymph flow (capillary filtration) indicates a heteroporous membrane system. For lymph flows greater than five times control, the solvent-drag reflection coefficients were: 0.59 +/- 0.11, 0.52 +/- 0.06, 0.66 +/- 0.05, 0.70 +/- 0.05, 1.01 +/- 0.04, and 1.05 +/- 0.03 for the six fractions. Osmotic reflection coefficients estimated from the minimal lymph-to-plasma concentration ratios were: 0.50 +/- 0.03, 0.59 +/- 0.02, 0.67 +/- 0.04, 0.72 +/- 0.03, 0.94 +/- 0.01, and 0.96 +/- 0.01 for the six protein fractions. The osmotic reflection coefficients are consistent with a two- "pore" exchange model possessing equivalent pore radii of 80 and 200 A. Theoretical considerations indicate that only the two largest protein fractions (100 A and 120 A radii) achieved filtration-independent concentrations in pulmonary lymph, even at the highest filtration rates. This suggests that the reported osmotic reflection coefficients of the four small protein fractions underestimate their true values.

Animals↗
PubMed1977

Advantages of a combination of proteolytic enzymes, flavonoids and ascorbic acid in comparison with non-steroid anti-inflammatory agents.

The action of a combination of chymotrypsin-trypsin + flavonoids + ascorbic acid (zymolean) has been compared with that of 7 non-steroid anti-inflammatory substances in 4 tests: a histamine induced wheal, dextran and carrageenin induced edemas, and permeability to Evans blue in the peritoneal cavity. 1. The non-steroid anti-inflammatory substances, which reduce markedly the carrageenin induced edema, are active against peritoneal permeability, but bring about almost no decrease in the effects of histamine and dextran. 2. The combination studied is effective in all of the techniques. 3. The reduction of capillary permeability induced by histamine is due to the action of flavonoids and ascorbic acid. 4. The action of the proteolytic enzymes, administered by duodenal route, on the one hand, and that of hesperidin-methylchalcone + methyl-4-esculetol + ascorbic acid on the other, accumulate to reduce the two types of edema. 5. The effect against permeability in the peritoneum seems to exerted by the combination of the flavonoids + ascorbic acid. 6. The combination studied, therefore, shows a more complete spectrum of action than the non-steroid anti-inflammatory substances against initial symptoms of inflammation.

Animals↗
PubMed1993

The effect of alpha human atrial natriuretic peptide on plasma volume and vascular permeability in normotensive subjects.

Low dose infusion of alpha human atrial natriuretic peptide (ANP) has been shown to cause a shift of intravascular fluid to the interstitial space. No studies have been reported on the effect of ANP on capillary permeability to plasma proteins. We studied the effect of low dose ANP (2.5 pmol/kg.min) or equal volume of saline control when infused over 90 min, on plasma volume, transcapillary escape rate of intravascular albumin, and the rate of reentry of albumin to the vascular space in eight normal subjects. Intravenous injection of 125I-human serum albumin was used for measurement of plasma volume and intravascular albumin escape rate. A significant ANP-induced fall in plasma volume (P < 0.01) was observed. Transcapillary escape rate of intravascular albumin when corrected for concurrent plasma volume changes showed a significantly greater escape during ANP infusion than during saline control (P < 0.05). The mean +/- SEM changes in plasma albumin concentration were +0.36 +/- 0.22 g/L.h during ANP infusion and -0.46 +/- 0.50 g/L.h during placebo. Plasma sodium, red cell volume, and urinary albumin and radioactivity remained unchanged. The mass of albumin reentering the circulation per hour showed no significant difference between the 2 days. In summary, low dose ANP infusion in healthy subjects caused a shift of plasma water and electrolytes from the circulation, with albumin escape as a secondary phenomenon.

Adult↗
PubMed2004

Studies on the anti-inflammatory effects of Clerodendron trichotomum Thunberg leaves.

Clerodendron trichotomum Thunberg Leaves (CTL) have been used for centuries in Chinese folk medicine for their anti-inflammatory properties. We have studied the anti-inflammatory effects of CTL extracts in rats, mice and in Raw 264.7 cells. 1 mg/kg solutions of the 30% and 60% methanol extracts of CTL were used and a 1 mg/kg of indomethacin was used as a positive anti-inflammatory standard; these were then administrated to rats. Carrageenan was injected subcutaneously to induce hind paw edema in rats. The result of carrageenan-induced rat paw oedema showed that a 1 mg/kg of the 30%, and 60% methanol fraction of CTL and 1 mg/kg of indomethacin inhibited the hind paw edema by 19.5%, 23.0%, and 20.5% respectively. The effect of CTL on inflammation in mice by a capillary permeability assay was examined by detecting Evans blue leakage from capillaries after the intraperitoneal injection of acetic acid, a potent inflammatory stimulus. The 60% methanol fraction of CTL inhibited Evans blue dye leakage by 47.0%, which was 10% higher than that of the inhibition of 1 mg/kg of indomethacin. Also, the 60% methanol fraction of CTL suppressed the prostaglandin E2 (PGE2) generation in RAW 264.7 macrophage cells after treatment with lipopolysaccharide (LPS) by as much as the inhibition of 1 mg/kg of indomethacin and this led to the synthesis of PGE2 by COX-2 induction. The inhibition of the carrageenan-induced rat paw oedema, vascular permeability and the PGE2 generation demonstrates that the 60% methanol fraction of CTL contains a potent anti-inflammatory activity.

Acetic Acid↗
PubMed1995

Quantitative analysis of dynamic Gd-DTPA enhancement in breast tumors using a permeability model.

The MRI signal enhancement in a breast tumor, measured as a function of time after a bolus injection of Gd-DTPA, may contain enough information to differentiate malignant from benign tissue. We find a physiological model for measuring capillary permeability and leakage space (P. S. Tofts, A. G. Kermode, measurement of the blood-brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts. Magn. Reson. Med. 17, 357-367 (1991)) fits the data well. The enhancement curve is particularly sensitive to the preinjection T1 of the tumor, the dose, and the time of injection. This model may provide a means of characterizing the pathophysiology of breast tumors from the Gd-DTPA enhancement curve.

Breast↗
PubMed1985

Endothelial fenestral diaphragms: a quick-freeze, deep-etch study.

The route by which water, solutes, and macromolecules traverse the endothelial cell has long been a subject of study for both physiologists and cell biologists. Recent physiologic studies describe a slit-shaped pore (5.1-5.7-nm wide) as the communicating channel, although no channel of such dimensions has been visible in electron microscopic preparations. That this channel should be found within the fenestral diaphragm has long been suggested. In this report, by the aid of a new technique in tissue processing, we are able to demonstrate a possible morphologic correlate within the fenestral diaphragm of fenestrated capillaries. Quick-freezing and deep-etching of whole tissue blocks allows the sublimation of water from the endothelial pores, thus leaving the channels through the diaphragms empty and readily replicated with a platinum-carbon shadow. The structure of the diaphragm was revealed thus to be composed of radial fibrils of 7 nm in diameter, interweaving in a central mesh, and creating by their geometric distribution, wedge-shaped channels around the periphery of the pore. The average channel had a maximum arc length of 5.46 nm. Fenestrated endothelia from various tissues, including endocrine and exocrine pancreas, adrenal cortex, and kidney peritubular capillaries, displayed the same diaphragmatic structure, whereas continuous capillaries in muscle had no such diaphragm. Photographic augmentation of electron micrographs of etched replicas displayed marked enhancement at n = 8, confirming an octagonal symmetry of the fenestral diaphragm. Finally, cationic ferritin, clearly visible as a marker after etching, heavily bound to the flowerlike structure within the fenestral pore. We conclude that the fenestral diaphragm contains the structure responsible for fenestrated capillary permeability and that the communicating channel has the shape of a wedge.

Animals↗
PubMed1989

Histamine release induced by proteolytic digests of human serum albumin: isolation and structure of an active peptide from pepsin treatment.

Treatment of human serum albumin with a proteolytic enzyme such as pepsin, alpha-chymotrypsin, cathepsin D or trypsin generated histamine releasing peptides. A low-molecular weight peptide (P-1) responsible for releasing histamine was isolated from peptic digests of human serum albumin by affinity chromatography on heparin-Ultrogel and reversed-phase high performance liquid chromatography. The amino acid sequence of the P-1 was estimated to be V-R-Y-T-K-K-V-P-Q-V-S-T-P-T-L by Edman degradation. The sequence determined appears to correspond to residues 409-423 of human serum albumin. Peptide P-1 produced dose-related histamine release from isolated rat mast cells in the concentration range of 1-50 microM. The intradermal injection of the P-1 (0.5 micrograms) increased capillary permeability in rats. This response was blocked by the antihistamine diphenhydramine.

Animals↗
PubMed1990

[An ultrastructural investigation of changes in hypoxia in the subependymal layer of the newborn rabbit].

Fetal and neonatal hypoxia is suggested as a noticeable risk factor related to the occurrence of subependymal hemorrhages. To investigate the cause of newborn subependymal hemorrhages, a 0 day old newborn rabbit was exposed to either 5 or 10 minutes hypoxia by N2 box. After exposure, the brain was observed by optical and electric microscope using horseradish peroxidase (HRP) as the protein tracer to study the change in the capillary permeability. The result obtained were as follows: 1) In the newborn rabbit blood gas analysis, PO2 (mmHg) decreased more in the 5 and 10 min hypoxia groups than the control group which used the N2 box. pH and BE changes were similar to PO2 (mmHg). On the other hand, PCO2 (mmHg) increased proportionately. These results indicated that this hypoxic method changed blood gas and caused acidosis. 2) In the optical microscopic examination, the 0 day old newborn rabbit brain was found to have a thin subependymal layer. We could not find obvious subependymal hemorrhage using optical microscope. 3) In the electric microscopic examination, HRP was found in the cavity of the brain capillary at the subependymal layer and was slightly incorporated into the pinocytic vesicle of the lumen on the control. Since the tight junction filled the roll out, HRP was not found outside the capillary. 4) The 5 min hypoxia group caused astrocyte foot swelling, edema and slight opening of the tight opening of the tight junction. HRP was passed through the tight junction, but not outside the capillary. 5) The 10 min hypoxia group caused destruction of astrocyte and edema around the capillary. The tight junction was more opened than in the 5 min hypoxia group and HRP leaked out of the capillary through the tight junction. From the findings mentioned above, it is suggested that our hypoxic model increased permeability of the capillary in subependymal layers and that this change might be the first ultrastructural change before the onset of subependymal hemorrhages.

Animals↗
PubMed1997

Electron microscopic demonstrations of filamentous molecular sieve plugs in capillary fenestrae.

The permeability of capillaries is usually explained with reference to "small pores," permeable to water and small solutes, and "large pores," permeable to proteins. Fenestrated capillaries are far more permeable to water and small solutes than nonfenestrated capillaries; moreover, the permeability is highest in the capillaries with the most fenestrae. This suggests that the small pores reside in the fenestral diaphragms; however, no such pores have been illustrated using electron microscopy. In an attempt to clarify this controversy, fenestrated capillaries in the small intestine, stomach, and kidney of the rat were reinvestigated by electron microscopy. A new method of vascular perfusion-fixation was employed, which included the use of glutaraldehyde dissolved in an oxygen-carrying blood substitute (fluorocarbon) and delivered by a peristaltic pump controlled by pressure feedback. The investigation disclosed a prominent endocapillary surface coat, about 50-100 nm thick, and the existence of bush-like filamentous sieve plugs in the fenestrae. Each filamentous plug was composed of 20-40 filaments, each filament measuring 300-400 nm in length and 5-10 nm in thickness. The filamentous plugs have tentatively been named fascinae fenestrae, because they resemble fascines and may also function as such.

Actin Cytoskeleton↗
PubMed1980

Mechanism of glucagon-induced intestinal secretion.

The effects of local intra-arterial glucagon infusion on transcapilary, lymphatic, and transmucosal fluid and protein fluxes were studied in autoperfused segments of cat ileum. The glucagon infusions resulted in a significant increase in intestinal blood flow, lymph flow, capillary filtration coefficient, capillary pressure, interstitial volume, and interstitial fluid pressure. Precapillary resistance and the pre-to-postcapillary resistance ratio decreased during the glucagon infusion. The transcapillary oncotic pressure gradient and the osmotic reflection coefficient were reduced, suggesting that capillary permeability is significantly increased with glucagon. Ultrastructural analysis of tissue samples acquired during the infusion of higher doses of glucagon indicates disruption of the mucosal membrane. An glucagon indicates disruption of the mucosal membrane. An alteration in mucosal structure is supported by the appearance of plasma proteins in the secreted fluid. The results of this study indicate that glucagon-induced intestinal secretion results from an alteration in capillary fluid balance, i.e., an increased capillary pressure and permeability.

Animals↗
PubMed2000

Vascular permeability factor/vascular endothelial growth factor in nasal polyps.

Although the aetiology of polyps is still, for the most part, unknown, the disease is known to involve tissue oedema. Vascular permeability/vascular endothelial growth factor (VPF/VEGF) is a major inducer of angiogenesis and capillary permeability. This study investigated VPF/VEGF expression in biopsies of nasal polyps from 39 patients and in healthy nasal mucosa from 10 patients by immunohistochemical staining. Staining for VPF/VEGF in the mucosal surface and in the glandular epithelium of nasal polyps was weaker than in normal controls. In two patients, strong staining for VPF/VEGF was found in a granular pattern in mast cells, while the mast cells in other polyposis patients appeared to be largely degranulated. VPF/VEGF was not seen in the mast cells of control patients. Although expression of VPF/VEGF was not increased in the epithelium of the nasal polyps, VPF/VEGF secreted from mast cells may take part in nasal polyp formation.

Adolescent↗
PubMed1999

Pulmonary capillary sieving of hetastarch is not altered by LPS-induced sepsis.

BACKGROUND: Gram-negative lipopolysaccharide (LPS) has been demonstrated to increase pulmonary capillary permeability as judged by the increased flow of protein-rich lymph from the lungs of sheep infused with LPS. This finding suggests that LPS-injured pulmonary capillaries might be less restrictive than uninjured capillaries to the filtration of large hetastarch molecules. Hetastarch has a broad molecular mass spectrum (35-1,500 kilodaltons (kDa)), and one way to test the restrictiveness of pulmonary capillaries is to measure the size of the largest hetastarch molecules that cross the microvascular barrier and enter the lymph. To evaluate the effects of LPS, we compared hetastarch molecular distributions in the lung lymph of normal and LPS-injured sheep. METHODS: Adult sheep (38.2 +/- 0.8 kg) were surgically prepared for the collection of lung lymph, with study initiation after a 5- to 7-day recovery period. Hetastarch (6%) was infused (10 mL/kg) 24 hours before study to allow for stabilization of the hetastarch molecular distribution. On the day of study, LPS (Escherichia coli lipopolysaccharide, 2 microg/kg; n = 6) was infused, and plasma and lymph samples were collected for 12 hours. An additional group of animals not infused with LPS (n = 6) served as controls. Hetastarch molecular distributions in plasma and lymph were measured by using high performance size exclusion chromatography. RESULTS: In control sheep, the largest hetastarch molecules in lymph averaged 861 +/- 18 kDa (mean +/- SEM) (plasma, 1,065 +/- 18 kDa). In LPS-treated sheep, the largest hetastarch molecules in lymph averaged 845 +/- 19 kDa (not significant vs. normal) (plasma, 1,025 +/- 14 kDa). Hetastarch concentrations in plasma and lung lymph of normal sheep, respectively, were 0.61 +/- 0.05% and 0.34 +/- 0.07%. In LPS-treated sheep, hetastarch concentrations in plasma and lymph were 0.56 +/- 0.08 (not significant vs. normal) and 0.29 +/- 0.07, respectively (p < or = 0.05). Lymph concentrations were lower after LPS because of increased lymph flows (19.9 +/- 5.4 mL/30 min, compared with 3.6 +/- 0.8 mL/30 min in normal sheep). CONCLUSION: Our results suggest that LPS does not alter the diameter of the largest pores perforating the walls of pulmonary capillaries. Rather, the number of these pores in the capillary wall appears to be increased. This increase would explain why lymph flows rise after LPS with little change in the lymph protein concentration. Our results are also consistent with a filtration model in which capillaries are assumed to be perforated by small pores (protein reflection coefficient = 1) as well as large pores (protein reflection coefficient = 0).

Animals↗
PubMed1997

Potassium and thallium uptake in dog myocardium.

UNLABELLED: We sought to ascertain the rates and mechanisms of uptake of markers for regional myocardial blood flows. METHODS: The rates of exchange of potassium and thallium across capillary walls and cell membranes in isolated blood-perfused dog hearts were estimated from multiple indicator dilution curves recorded for 131I-albumin, 42K and 201Tl from the coronary sinus outflow following injection into arterial inflow. Analysis involved fitting the observed dilution curves with a model composed of a capillary-interstitial fluid-cell exchange region and nonexchanging larger vessels. RESULTS: Capillary permeability surface products (PSc) for potassium and thallium were similar, 0.82 +/- 0.33 (mean +/- s.d., n = 19) and 0.87 +/- 0.32 ml min-1 g-1 (n = 24) with a ratio for simultaneous pairs of 1.02 +/- 0.27 (n = 19). For the myocardial cells, PSpc averaged 3.7 +/- 3.1 ml min-1 g-1 (n = 19) for K+ and 9.5 +/- 3.9 (n = 24) for Tl+; the ratio of potassium to thallium averaged 0.40 +/- 0.19 (n = 18), thereby omitting a single high value for potassium. This high cellular influx for thallium is interpreted as due to its passage through ionic channels for both Na+ and K+. CONCLUSION: The high permeabilities and large volumes of distribution make thallium and potassium among the best ionic deposition markers for regional flow. Their utility for this purpose is compromised by significant capillary barrier limitation retarding uptake; so regional flow is underestimated modestly in high-flow regions particularly.

Animals↗
PubMed1969

The action of glucosulphone [N,N'-di (glucose sodium sulphonate) of 4,4'-diaminodiphenyl sulphone] on pancreatic kallikrein.

1. The effects of sulphone have been studied on kinin production in dog plasma and on capillary permeability in the skin of rabbits.2. Dog plasma was used as a substrate for pancreatic kallikrein in vitro and the addition of sulphone caused an inhibition of kinin production, which was dependent on the concentration of the drug.3. The increased vascular permeability produced in vivo by intradermal injections of kallikrein was partially inhibited by sulphone injected intravenously. The same doses of sulphone also inhibited the increase in permeability produced by bradykinin and histamine in the skin of rabbits.

Animals↗
PubMed1979

Capillary diffusion capacity for I-131 and capillary filtration rate in female patients with idiopathic oedema.

In female patients with idiopathic oedema the capillary filtration rate and capillary diffusion capacity for I-131 were studied in lower-limb muscles and subcutaneous tissue. The capillary filtration rate averaged 0.276 ml/100 ml per minute, and the capillary diffusion capacity for I-131 averaged 9.8 mol/(mol/ml) per 100 g per minute in the gastroonemius muscle and 8.7 mol/(mol/ml) per 100 g per minute in the lower-limb subcutaneous tissue. All of these figures are statistically significantly higher than the corresponding control findings. The results are compatible with the concept of disturbed capillary permeability, and etiopathogenetic factor of idiopathic oedema.

Adolescent↗
PubMed1977

Transcapillary exchange of 14C-inulin by free diffusion in channels of fused vesicles.

Capillary permeability for the extracellular, hydrophilic indicator 14C-inulin, was determined in the autoperfused cat gastrocnemius muscle by bolus injection, venous sampling expts. The capillary diffusion capacity, CDC (the permeability-surface are product, PS), was 0.84 ml/100 g-min, and capillary extraction, E, was 0.307 at a plasma flow of 4.0 ml/100 g-min as average values of 7 expts. Results were compared with 51Cr-EDTA and 57Co-B12 data of previous studies. The findings imply that 14C-inulin is not subject to restricted diffusion across the continuous capillary membranes of skeletal muscle as compared to 51Cr-EDTA as well as 57Co-B12. These hydrophilic indicators pass the capillary barrier at rates proportional to their respective free diffusion coefficients in water. The Pappenheimer equivalent pore radius estimate of 30 A (or slit width of 37 A) and the Karnovsky 40 A interendothelial slit width are inconsistent with the present data which imply a much larger pore size. The transendothelial channel system of fused vesicles is a possible morphological equivalent for the present findings which support the general theory that capillaries of continuous type exhibit similar permeation characteristics regardless of the tissue in which they are located. By kinetic black-box analysis the extravascular distribution volume for 14C-inulin in skeletal muscle was found to be 13.0 ml/100 g. The data indicate that 51Cr-EDTA, which has about the same molecular radius as sucrose, and 14C-inulin have identical extravascular volumes of distribution and that both molecules presumably enter the sarcoplasmic reticulum.

Animals↗
PubMedDate not supplied

The gliovascular interphase in irradiated brain tissue. Electron microscopic investigations. Horseradish peroxidase transport.

The gliovascular interphase in irradiated brain tissue. Electron microscopic investigations. Horseradish peroxidase transport. Acta physiol. pol., 1979, 30 (4): 455--468. The gliovascular junction which is the morphological element of the blood-brain barrier was studied. For damaging the barrier 44 Wistar rats received single dose of 800 rads of gamma radiation from Co60. The observations were carried out in electron microscope and capillary permeability was tested by means of horseradish peroxidase. It was found that: astrocytes play a significant role in the normal function of the barrier maintaining efficient active transport, the capillary vessel is a barrier to transport of macromolecular substances which cannot pass into the brain tissue under normal conditions.

Animals↗
PubMed2003

Selective opening of the blood-tumor barrier by a nitric oxide donor and long-term survival in rats with C6 gliomas.

OBJECT: The response of brain tumors to systemic chemotherapy is limited by the blood-tumor barrier (BTB). Nitric oxide (NO) has been implicated in the regulation of vascular permeability and blood flow. The authors evaluated the effects of exogenous NO, which was released from a short-acting NO donor (Proli/NO), and those of NO metabolites on the capillary permeability of tumors and normal brain tissue by using quantitative autoradiography in a C6 glioma model in rats. METHODS: The Proli/NO was infused at a wide dose range (10(-2) to 10(-12) M) either intravenously or into the internal carotid artery (ICA) and demonstrated substantial tumor-selective increases in blood-brain barrier (BBB) permeability in response to various-sized tracers ([14C]aminoisobutyric acid, [14C]sucrose, [14C]dextran). Internal carotid artery or intravenous administration of sodium nitrite had a comparable effect on BTB permeability. The NO effect on microvascular permeability could be obtained without causing hemodynamic side effects. The effect of NO on the efficacy of carboplatin chemotherapy was investigated in intracerebral C6 gliomas. Simultaneous intravenous infusions of Proli/NO (10(-6) M) and carboplatin (20 mg/kg) led to long-term survival in 40% of rats harboring intracerebral C6 gliomas compared with control animals receiving ICA or intravenous infusions of carboplatin, Proli/NO, or vehicle alone. No residual tumor was demonstrated on histological or magnetic resonance imaging studies performed in rats treated with Proli/NO and carboplatin, and no toxicity was observed. CONCLUSIONS: This new approach demonstrated the in vivo efficacy and safety of NO and nitrite in enhancing the delivery of systemically delivered radiolabeled tracers and carboplatin into rat gliomas. The NO-induced tumor-selective BBB disruption and intravenous carboplatin chemotherapy may be more efficacious than current chemotherapy strategies against brain tumors.

Animals↗