Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Capillary Permeability”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,135 records · Page 63Linked to original sources

Use of [3H]methylglucose and [14C]iodoantipyrine to determine kinetic parameters of glucose transport in rat brain.

Local maximal velocities of transport (Tmax) and the half-maximum transport constants (KT) for glucose transport across the blood-brain barrier have been determined in local regions of the brain in normal conscious rats. [14C]iodoantipyrine and [3H]methylglucose were infused together intravenously for 2 min in rats with plasma glucose concentrations maintained at different levels, and the time courses of the tracer levels in arterial blood were measured. Local 14C and 3H concentrations were then measured in tissue samples dissected from the frozen brains. By comparing the transport-limited uptake of [3H]methylglucose with the blood flow-limited uptake of [14C]iodoantipyrine, the value of m, a factor between 0 and 10 that accounts for diffusion and/or transport limitations, was derived, and from the equation, m = 1 - PS/F (where PS is capillary permeability-surface area product and F is cerebral blood flow), the permeability-capillary surface area for methylglucose was calculated (S. S. Kety. Pharmacol. Rev. 3: 1-41, 1951). Values for Tmax and KT for glucose were calculated by application of Michaelis-Menten kinetic relationships adapted for the competition for transport between glucose and methylglucose. Tmax was determined in three representative gray structures and one white structure of the brain: Tmax was 5.3 +/- 0.3 (SD) mumol.g-1.min-1 in the gray structures and 4.3 mumol.g-1.min-1 in the white structure. KT was 3.6 +/- 0.4 (SD) mM in the gray structures and 5.9 mM in the white structure. This approach allows the simultaneous determination of local values of Tmax and KT for glucose and the rates of blood flow in various regions of the brain in conscious animals.

3-O-Methylglucose↗

[Drugs for veno-lymphatic insufficiency].

Treatment of venous and lymphatic insufficiency of the lower limbs is based on 3 components: elastic support, venotonic drugs and radical treatments (surgery or sclerotherapy) of insufficient veins. Venotonic drugs have specific indications limited to functional impairment: heavy feeling in the legs, pain and impatience in the evening. There are different categories of venolymphatic drugs. Flavonoids have various pharmacological actions, most notably an increase in venous tone, reduction of capillary permeability and increase of capillary resistance. Choice of a venotonic drug is funded on knowledge of pharmacodynamics and pharmacokinetics of the molecule, critical evaluation of clinical studies, physician's personal experience and drug cost. Venotonic drugs are useful when venous insufficiency leads to functional manifestations. They are especially the treatment of heavy leg syndromes during warm seasons when elastic support is uncomfortable.

Adenosine Diphosphate↗

Cerebrovascular responses to soman: time and dose dependent effects.

The effects of convulsant and subconvulsant doses of soman on cerebral blood flow (rCBF) and permeability-capillary surface area products (rPS) were examined in 15 brain regions at 1 hr, 24 hr and 1 week after injection in male, Sprague-Dawley rats. Brain histology was examined 3 days after injection. A convulsant dose of soman (70 micrograms/kg, sc) produced large increases in blood flow in all brain regions 1 hr after injection. Such elevations were still observed in 7/15 brain regions 1 day later and in 2/15 regions (septal area and basal ganglia) 1 week later. Similarly, rPS was significantly elevated in every brain region at 1 hr after injection, in 11/15 brain regions at 24 hr, and 4/15 regions 1 week later. Blood pressure peaked at 1 hr and remained well above control levels (115 mm Hg) for 5 hr after drug administration. A subconvulsant dose of soman (33 micrograms/kg) led to a significant, though less dramatic increase in blood flow in all brain regions within 1 hr but not at 1 day or 1 week after injection. In contrast, rPS increases were generally small except in hind-brain structures at 1 hr and 1 day after agent injection. By 1 week however, rPS values appeared to be rising generally and were significantly elevated in the olfactory bulbs and tubercle, as well as hindbrain regions. At this dose, blood pressures were unchanged from control levels (110-120 mm Hg) at all time periods. At 72 hr following injection of a convulsant dose of soman, severe and extensive cellular changes were found in 11/17 regions. After a subconvulsant dose, such abnormalities were still observed in 6/17 brain regions. The data strongly indicate that soman exposure can produce prolonged regional effects on cerebrovascular functions and neuronal integrity even in the absence of physiologic or behavioral evidence of seizure activity or sustained elevations of blood pressure.

Animals↗

[Effects of methylprednisolone on tumor-induced brain edema].

Local cerebral blood flow (LCBF), local cerebral glucose utilization (LCGU) and capillary permeability were studied in rats with tumor-induced brain edema. Moreover, effects of methylprednisolone on these physiological parameters were studied to analyse a possible role of steroid on treatment of peritumoral brain edema. A cubic millimeter pellet of Walker 256 tumor was transplanted to the left sensorimotor cortex of the rat brain. Animals were randomly divided into two groups. One group was treated with methylprednisolone (15 mg/kg/day) for 5 days starting at 5 days after tumor inoculation, and the other group received no treatment. These rats were used for autoradiographic study at 10 days after tumor inoculation. Local CBF, LCGU and capillary permeability were measured with 14C-iodoantipyrine, 14C-deoxyglucose and 14C-alphaaminoisobutyric acid, respectively. In the untreated group, LCBF and LCGU were widely depressed in the cortex and deep structures of the hemisphere ipsilateral to the tumor. Of the methylprednisolone treated animals LCBF and LCGU were significantly better than that of untreated animals. Capillary permeability of the untreated animals were highly increased in the viable part of the tumor. Some increase was also noted in the peripheral edge of the tumor and adjacent brain. In the methylprednisolone treated groups, capillary permeability was significantly lower than that in untreated group. The data suggest that methylprednisolone decreases capillary permeability in the viable part of the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The role of vascular endothelial growth factor and interleukins in the pathogenesis of severe ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is a dramatic complication of ovulation induction. In its most severe form, OHSS is characterized by massive cystic enlargement of the ovaries associated with third space fluid shift, resulting in the formation of ascites and pleural effusion. Ascites developes because of increased peritoneal capillary permeability. In this study we examined the role of vascular endothelial growth factor (VEGF) and interleukins in the pathogenesis of increased capillary permeability. VEGF is a member of the family of heparin binding proteins that act directly on endothelial cells to induce proliferation and angiogenesis. VEGF mRNA and protein are expressed by human ovarian granulosa and theca cells late in follicular development and subsequent to ovulation by granulosa and theca cells. Therefore, VEGF is ideally positioned to provoke the increased permeability of theca blood vessels that occurs shortly before ovulation. Hybridization studies in the rat and primate ovary have demonstrated VEGF mRNA expression predominantly after the luteinizing hormone (LH) surge known to be essential for OHSS. The gonadotrophin-releasing hormone antagonist results in a decreased mRNA expression, implying such expression is dependent on LH. The expression of VEGF mRNA has been recently shown to be enhanced by human chorionic gonadotrophin (HCG) in a dose- and time-dependent fashion. These studies confirm the timely association between VEGF and HCG that has been clinically known for many years to be integral in the development of OHSS. VEGF concentrations in serum, peritoneal fluid and follicular fluid of patients at risk for OHSS have been shown to be significantly related to the development of the syndrome. Furthermore, the kinetics of VEGF in the plasma of patients who actually develop severe OHSS are closely correlated with the clinical course of the syndrome and with certain biological characteristics of OHSS and of capillary leakage, such as leukocytosis and increased hematocrit. Studies on ascitic fluid from patients with sever OHSS have proved that VEGF is the major capillary permeability agent. Incubation with VEGF antiserum decreased the vascular permeability activity by 70%. Interleukin-2 (IL-2) is the first of a series of lymphocytotrophic hormones to be recognized as pivotal for the regulation of immune response. However, hard data to confirm its central role in the pathogenesis of OHSS are still lacking, despite the fact that some preliminary studies suggest a positive association between the pooled follicular fluid IL-2 concentration and the development of OHSS. IL-6 is a mediator of the acute phase response to injury, a systemic reaction characterized by leukocytosis, increased vascular permeability and increased synthesis of acute phase proteins by the liver. Significantly higher serum and ascites IL-6 concentrations were seen in OHSS patients. The immunohistochemical localization pattern suggested that IL-6 is LH or HCG dependent. However, the use of IL-6 as a predictor for the occurrence of OHSS has not been successful. The kinetics of IL-6 in patients with severe OHSS are correlated with the clinical symptoms and the biochemical parameters known to be associated with the severity of the syndrome, suggesting a possible role for IL-6. Further molecular biology studies similar to those performed on VEGF are needed to confirm if this interleukin is central in the cascade of events. IL-8 is a chemoattractant, activating cytokine and a potent angiogenic agent. The peritoneal fluid levels is increased in patients with severe OHSS; its concentration in peritoneal fluid is increased inpatients with severe OHSS. The place of this interleukin in the cascade of events is as yet undetermined and further studies are needed. In conclusion, molecular biology and clinical studies strongly suggest that VEGF is the principal mediator by which HCG might increase capillary permeability in OHSS.

Animals↗

Molecular cloning of capillary permeability-increasing enzyme-2 from Agkistrodon caliginosus (Korean viper).

The gene of capillary permeability-increasing enzyme-2 (CPI enzyme-2) was cloned from the cDNA library of Agkistrodon caliginosus and its nucleotide sequence was determined. Its sequence indicates that CPI enzyme-2 is synthesized as a pre-zymogen of 258 amino acid residues, including a putative secretory signal peptide of 18 amino acids and a proposed zymogen peptide of 6 amino acids. The amino terminal sequence deduced from the cDNA sequence was exactly consistent with that of CPI enzyme-2 except for the substitution of an amino acid (Gly27-->Ser). The open reading frame is very similar to those of plasminogen activator and thrombin-like proteases cloned from other snakes. The clone encoding CPI enzyme-2 belongs to the serine protease family. The active site of the enzyme is highly conserved at His41, Asp86 and Ser180. Its possible glycosylation sites, Asn-X-Thr/Ser, are located at amino acid residues 20-22, 55-57, 79-81 and 97-99.

Agkistrodon↗

Large capillary fluid permeability in skeletal muscle and skin of man as a basis for rapid beneficial fluid transfer between tissue and blood.

Our previous studies strongly indicate that the capillary filtration coefficient (CFC) in skeletal muscle and skin of man is much larger than previously believed, or about 0.050 ml min-1 100 ml-1 mmHg-1. The hypothesis that this large capillary fluid permeability is a factor of primary importance for plasma volume control was approached. Experimental hypovolaemia induced by lower body negative pressure (LBNP of 70-95 cmH2O) was associated with a rapid net fluid gain from the studied upper arm into the circulation of 0.17 ml min-1 100 ml-1 tissue. The transcapillary driving force for this fluid transfer, probably caused by adrenergic adjustment of vascular resistance, with a decline of capillary pressure, was relatively small, or 1.7 mmHg on average. CFC was instead very high during LBNP, increasing from a control value of 0.054 +/- 0.004 (SE) to no less than 0.097 +/- 0.007 ml min-1 100 ml-1 mmHg-1, probably reflecting an increased number of effectively perfused capillaries. It is suggested that the large capillary fluid permeability in skeletal muscle and skin of man, with large tissue mass and fluid reservoir, may be of great functional importance for plasma volume control after blood loss and also in other (patho)physiological situations. As demonstrated, it can thus permit rapid transfer of large fluid volumes into the circulation and, perhaps of special importance, with only small transcapillary driving force (capillary pressure decline).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

Effect of TYB-2285 on peritoneal anaphylaxis in passively sensitized rats.

1. The effect of TYB-2285, a novel anti-inflammatory drug, was investigated on passive peritoneal anaphylaxis in rats, and compared with disodium cromoglycate (DSCG), amlexanox, ketotifen fumarate and tranilast. 2. As parameters of passive peritoneal anaphylaxis, histamine release into the peritoneal cavity and capillary permeability elicited by ascitis were measured. 3. TYB-2285 (10 mg/kg), when given intraperitoneally at 0.5, 1 and 2 min before antigen challenge, inhibited anaphylactic histamine release by 36.2%, 57.5% and 52.6%, respectively. TYB-2285 also inhibited capillary permeability by 20.9%, 57.6% and 49.0%, respectively. 4. DSCG (10 mg/kg), given intraperitoneally 0.5 min before challenge, inhibited histamine release and capillary permeability by 79.6% and 57.6%, respectively. 5. Amlexanox (10 mg/kg), given intraperitoneally 0.5 min before challenge, inhibited histamine release and capillary permeability by 85.6% and 74.8%, respectively. 6. A time-course study showed that TYB-2285 (30 mg/kg) was effective for 30 min after oral administration. A dose-response study suggested that the inhibitory effect of TYB-22585 (postoperatively) on histamine release during PPA reached a plateau at 10 mg/kg. 7. In passive peritoneal anaphylaxis in vitro, TC-1121 and TC-1122, metabolites of TYB-2285, inhibited antigen-induced histamine release at 10(-7) to 10(-5) M in a dose-dependent manner, whereas TYB-2285 itself and other major metabolites of TYB-2285, TC-286 and TC-326, did not inhibit histamine release, even at 10(-4) M.

Anaphylaxis↗

Tumor necrosis factor-alpha-induced gelatinase B causes delayed opening of the blood-brain barrier: an expanded therapeutic window.

Proteolytic damage is a late event in the molecular cascade initiated by brain injury. Earlier, we proposed that matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA) are important in secondary brain injury. We have shown that intracerebral injection of activated 72-kDa type IV collagenase (gelatinase A) opens the blood-brain barrier, and that during hemorrhagic brain injury there is endogenous production of 92-kDa type IV collagenase (gelatinase B) and uPA. Therefore, to study the functional link between proteolytic enzymes and blood-brain barrier damage, we induced MMP expression by infusing tumor necrosis factor-alpha (TNF) intracerebrally in rats. Initially, the effect on capillary permeability of increasing doses of TNF, using [14C]sucrose uptake, was measured. Then, the time-course of the capillary permeability change was studied at 4, 16, 24 and 72 h. Expression of MMP and uPA was measured by zymography at 24 h after TNF injection and compared to saline-injected controls. A dose-dependent increase in capillary permeability was seen 24 h after TNF injection. Maximal uptake of [14C]sucrose occurred at 24 h compared to saline-injected controls (P < 0.05). Zymography showed production of gelatinase B, which was significantly greater than in saline-injected controls at 24 h (P < 0.05). Batimastat, a synthetic inhibitor to metalloproteinases, reduced sucrose uptake at 24 h (P < 0.0001), and was effective even when given 6 h after TNF (P < 0.01). Thus, gelatinase B is the intermediate substance linking TNF to modulation of capillary permeability. Agents that interfere with transcription of proteolytic enzymes or block their action may reduce delayed capillary injury, extending the therapeutic window.

Animals↗

Simultaneous Determination of Two-Phase Relative Permeability and Capillary Pressure of Porous Rocks from Steady-State Flow Experiments: Accounting for Gravitational Forces and Fluid Compressibility.

A methodology for simultaneously measuring two-phase relative permeability and capillary pressure of porous rock samples from steady-state flow experiments, reported by Virnovsky et al. in 1995, is considered. The method requires measuring pressure drops in individual fluid phases across a rock sample. This paper studies the role of gravitational forces, neglected in the original derivation of the method. Direct numerical simulations of steady-state vertical flow experiments, performed over a typical range of rocks and flow parameters, show that the error caused by neglecting gravitational forces in the original method, is acceptable even for extremely high ( approximately 10(-10) m2) permeability samples. Thus, if multiphase flow measurements are performed on vertical samples, the gravitational force can be neglected for estimating relative permeability and capillary pressure. An extension of this method to the case of compressible fluids is presented. Copyright 1998 Academic Press.

Journal Article↗

Microvascular effects of selective prostaglandin analogues in the eye with special reference to latanoprost and glaucoma treatment.

Prostaglandin F(2alpha) analogues have recently been introduced on the market for glaucoma treatment. While these drugs have a well-documented intraocular pressure reducing effect only a limited number of studies have been published regarding their effects on the microvasculature in the eye. Since many naturally occurring prostaglandins have marked effects on the cardiovascular system it is conceivable that synthetic prostaglandins used as glaucoma drugs may exert microvascular effects in the eye, even if they exhibit receptor selectivity. Latanoprost, the active principle of Xalatan((R)) eye drops, is a selective FP prostanoid receptor agonist, and much of the paper is focused on the microvascular effects of latanoprost and some closely related prostaglandin analogues. The purpose of the paper is to review the literature on the microvascular effects of prostaglandins in the eye, and to present some unpublished data on the effects of selective prostaglandin analogues. Most of the prostaglandin analogues studied exhibit selectivity for the FP prostanoid receptor. Results from studies with the following prostaglandin analogues are presented in the paper: PGF(2alpha)-isopropyl ester (PGF(2alpha)-IE), 17-phenyl-18,19,20-trinor-PGF(2alpha)-isopropyl ester (17-phenyl-PGF(2a)-IE), 15-keto-17-phenyl-18,19, 20-trinor-PGF(2alpha)-isopropyl ester (15-keto-17-phenyl-PGF(2a)-IE), 13,14-dihydro-17-phenyl-18,19,20-trinor-PGF(2alpha)-isopropy l ester (latanoprost), 13,14-dihydro-15R,S-17-phenyl-18,19, 20-trinor-PGF(2alpha)-isopropyl ester (PhXA34), 17-phenyl-18,19, 20-trinor-PGE(2)-isopropyl ester (17-phenyl-PGE(2)-IE), and 19R-hydroxy-PGE(2) (19R-OH-PGE(2)). The regional blood flow has been determined with radioactively labelled microspheres, the blood volume with (51)Cr labelled erythrocytes and the capillary permeability to albumin with (125)I and (131)I labelled albumin. PGF(2alpha)-IE has been shown to exert marked microvascular effects in the rabbit anterior segment including vasodilatation, increased capillary permeability, and a breakdown of the blood-aqueous barrier. 17-phenyl-PGF(2alpha)-IE, 15-keto-17-phenyl-PGF(2alpha)-IE, and PhXA34/latanoprost exerted significantly less vasodilatory effect, and little effect on capillary permeability was seen with the FP receptor agonists when studied with Evans blue. Intravenous administration of PhXA34 at a dose range of 1-100 microg/kg b.w. had no consistent effect on the regional blood flow in the eye indicating that FP receptors in the ocular blood vessels are not expressed in the rabbit, or alternatively are not functionally coupled to regulation of vascular tone. In cats topical application of PGF(2alpha)-IE had no significant effect the on the regional blood flow in cannulated eyes. No blood flow experiments were performed in intact eyes with PGF(2alpha)-IE. 17-phenyl-PGF(2alpha)-IE and latanoprost caused some vasodilation in the anterior segment. None of the analogues had any significant effect on the blood volume in the ocular tissues, but an increase in capillary permeability to albumin was seen in several tissues of the eye. However, in the eyelid, nictitating membrane and conjunctiva exposed to high concentrations of the prostaglandins no or only little leakage of albumin was detected. It appears that the intraocular microvasculature in the cat exhibits some sensitivity to FP prostanoid receptor agonists. (ABSTRACT TRUNCATED)

Animals↗