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Biomedical subjects

B Gerdin

Publications and source records attributed to B Gerdin.

At least 163 records · Page 9Linked to original sources

Angiotensin converting enzyme dependent and non-dependent effects of a fibrinogen-derived pentapeptide on microvascular permeability in rat skin.

A permeability-increasing pentapeptide, termed peptide 6A, derived from plasmin-degraded human fibrinogen and known to potentiate the increase in microvascular permeability caused by bradykinin was investigated concerning its angiotensin converting enzyme (A.C.E.) related effects. When applied to a rat skin model together with a specific inhibitor of this enzyme, peptide 6A showed a potentiated effect after 30 min. but not after 5 min. The same was also true for bradykinin. These findings suggest that the degradation rate of these peptides is decreased with resulting prolongation of the period of leakage, when the action of A.C.E. is opposed. It is deduced that peptide 6A may act as a partial antagonist of this enzyme in the rat skin model. Addition of peptide 6A to a mixture of bradykinin together with inhibitors of the enzymes degrading bradykinin before application to the rat skin, significantly augmented the extravasation of 125I-albumin. These findings are consistent with data indicating that peptide 6A is a prostacyclin-releaser able to induce vasodilation. This effect of peptide 6A on the microcirculation seems to be separate from its angiotensin converting enzyme-related effects.

Animals↗

Inhibitory effect of the flavonoid O-(beta-hydroxyethyl)-rutoside on increased microvascular permeability induced by various agents in rat skin.

Flavonoids are used clinically in conditions with inflammatory oedema. The effects of a clinically employed flavonoid preparation, O-(beta-hydroxyethyl)-rutoside, in this paper abbreviated 'HR', were studied in a rat skin model designed to evaluate the leakage of 125I-labelled human serum albumin after intracutaneous injection of substances increasing microvascular permeability. Intravenous injection of 25-500 mg HR/kg body weight (b.w.) 30 min before administration of permeability-increasing agents gave a dose-related attenuation of the permeability increase due to histamine, bradykinin and fibrin degradation products. The maximum inhibitory effect of HR was observed at 250 mg/kg b.w.. Treatment with the beta 2-receptor agonist terbutaline also reduced the increased permeability. This effect of HR and terbutaline included reduction of oedema due to formaldehyde, citrate and dextran 70. The effect of terbutaline was counteracted by the beta-receptor blocker propanolol. The effect of HR on blood flow in the skin, determined as clearance of 133Xe, was not considered important as an explanation for its inhibition of microvascular permeability.

Animals↗

Enhancement of the permeability-increasing effect of bradykinin and substance P by a peptide derived from fibrinogen.

Two low molecular weight fibrin(ogen) degradation products, 6A (Ala-Arg-Pro-Ala-Lys) and 6D (Ser-Gln-Leu-Gln-Lys-Val-Pro-Pro-Glu-Trp-Lys) that are known to increase vascular permeability were injected together with bradykinin, substance P, neurotensin, histamine or tuftsin into the dorsal skin of rats. Effects on microvascular permeability were evaluated as leakage of intravenously injected 125I-labelled human serum albumin to tissues. It was found that peptide 6A potentiated the leakage caused by bradykinin and also, to a minor extent, that caused by substance P over a 30 min period, but not of any other substance. Peptide 6D increased bradykinin-induced leakage to a lower degree than did peptide 6A. Thus, it is shown that products resulting from fibrinolysis exert a selective effect upon the action of bradykinin and of substance P.

Animals↗

Myocardial infarction without coronary occlusion. A morphologic study in sheep.

The macroscopic, histologic and enzyme-histochemical characteristics of the myocardial lesion obtained after heating of a thermoprobe in a branch of the left coronary artery in sheep is reported. In 13 sheep such myocardial lesions were produced distal to the location of the thermoprobe. Alterations were observed in accordance with generally accepted morphologic criteria for myocardial infarction. The coronary artery branch in which the thermoprobe was located showed erythrocyte and platelet aggregates immediately after the heating episode, which disappeared within a few min, as demonstrated by coronary arteriography. Injection of radiolabelled microspheres into the coronary circulation after induction of the myocardial lesion, cryosectioning of the heart and autoradiography revealed a lack of blood flow in the damaged myocardial region. We consider this new method a suitable tool for further studies on the complex pathology involved in the development of myocardial infarction.

Animals↗

Use of 125I-labeled human serum albumin for quantitation of microvascular permeability in rat skin: reevaluation of an old method for studies on substances with an enhancing effect on microvascular permeability.

A method of determining the leakage of 125I-labeled human serum albumin in the plasma into a standardized area of rat skin to study the effects of intracutaneous application of vasoactive substances on microvascular permeability, was reevaluated. The effect is expressed as a quotient (Q) between the amount of labeled albumin in the test area and that in an area injected with buffer. This calculation is simple and as reliable as more complicated expressions of activity. Within a limited dose range, linear/log dose-response curves can be obtained after application of histamine or bradykinin. Locally injected 125I-labeled human serum albumin is eliminated very slowly from rat skin and determination of the amount of radiolabeled albumin in skin after an intravenous injection therefore represents leakage from the vascular compartments. The potentialities and advantages of this method in pharmacological studies are stressed.

Adenosine↗

Protective effect of angiotensin II inhibition on acute renal failure after intravascular coagulation in the rat.

Infusion of thrombin and the fibrinolysis inhibitor tranexamic acid during ether anaesthesia in the rat gives rise to fibrin deposition in the renal glomeruli. This resulted in renal insufficiency as indicated by an increase in the serum urea nitrogen, reduction in the renal blood flow and patchy cortical necrosis in the kidneys. The plasma renin activity was elevated initially probably due to the ether anaesthesia. Infusion of the angiotensin II antagonist saralasin prevented the renal insufficiency if it was given during the thrombin infusion but not if it was given afterwards. The deposition of fibrin in the kidneys was also reduced. The results indicate that angiotensin II is involved in the pathogenesis of the renal injury.

Acute Kidney Injury↗

Structure-activity studies on synthetic analogs to vasoactive peptides derived from human fibrinogen.

Counterparts to two vasoactive peptides previously isolated from fibrin(ogen) degraded by plasmin (EC 3.4.21.7) were synthesized by the solid phase procedure. The synthetic undecapeptide (Ser-Gln-Leu-Gln-Lys-Val-Pro-Pro-Glu-Trp-Lys) was isolated in a homogeneous state by chromatography on Sephadex G-25 and DEAE-Sepharose CL-6B and the pentapeptide (Ala-Arg-Pro-Ala-Lys) by chromatography on BioGel P-6 and column zone electrophoresis. The effect of these two peptides and of fifteen analogs to the pentapeptide on microvascular permeability in rat skin was investigated. The two synthetic counterparts were as potent as the natural peptides. With respect to the analogs, the influence of different functional groups was first studied. This was followed by attempts to minimize the active structure, induce or relieve rigidity of the peptide back-bone or otherwise accomplish modifications by a change in chirality at critical positions. Our results show that the tetrapeptide Arg-Pro-Ala-Lys has the same effect on microvascular permeability as the pentapeptide in the assay system used. Basic amino acids at both ends, as well as a proline residue adjacent to the N-terminal amino acid appear important for full or essentially full activity. On the other hand, substitution of the Ala at position 4 with several other amino acids did not result in a significant loss in biological potency.

Capillary Permeability↗

Comparison between predicted cause of death and cause of death found at autopsy in medicolegal autopsy material.

The question whether an autopsy could have been omitted without adversely affecting diagnostic accuracy in cases in which an unnatural death was not suspected, was investigated by evaluating data from the files of cases handled in 1977 at the Government Department of Forensic Medicine in Uppsala in which the police had requested a simple medicolegal examination. The police report and the result of an external examination were evaluated blindly and cases divided into three groups. In 95 cases (12%) no autopsy, in 360 cases (45%) a partial autopsy, and in 346 cases (43%) a complete autopsy was considered necessary. In three of the 95 cases and in four of the 360 cases a wrong diagnosis was made. In 59 cases (7%) a complete medicolegal examination was performed. In 21 of the latter the circumstances of death were obscure and in 11 of these an unnatural cause of death was found. The investigation confirms that all cases must be handled by skilled medicolegal experts, that the extent of the medicolegal examination can well be assessed by the physician in charge, and that the autopsy procedure can be simplified in many cases and omitted in some, especially in a situation where resources are limited, without significantly affecting diagnostic accuracy in the individual case. However this policy adversely affects scientific studies on larger autopsy material.

Autopsy↗

Effect of alpha-receptor blockade on the rate of fibrin elimination from the rat lung.

In rats with pharmacologically blocked alpha-receptor sites intravascular coagulation was induced by an intravenous injection of thrombin. The fibrin elimination from the lungs was greatly delayed in rats treated with the alpha-receptor blocking agent phenoxybenzamine one hour before the thrombin injection; whereas, in rats given the same substance 48 hours before this injection, no influence on fibrin elimination was seen. Infusion of albumin counteracted the effect on fibrin elimination in the former rats. A synergistic effect of phenoxybenzamine and the fibrinolysis inhibitor AMCA on the elimination of fibrin from the lungs was found. Circulatory mechanisms seem most reasonably to underlie the effect of phenoxybenzamine on fibrin elimination. No changes in fibrinolysis parameters were observed.

Adrenergic alpha-Antagonists↗

Pulmonary microembolism during and after aortic cross-clamping in heparinized and non-heparinized pigs.

The occurrence of pulmonary microembolism after aortic clamping and declamping was investigated in 21 young pigs. The prophylactive effect of heparin was also examined. Eight animals were heparinized, while 13 did not receive heparin. In 15 pigs the plasma concentration of fibrinogen was determined before, during and after clamping of the aorta. External detection of 51Cr-labelled platelets and 125I-labelled fibrinogen was performed. Lung tissue from these animals was homogenized and analysed for radioactivity. Specimens were taken from the lungs of all animals for morphological investigation. A significant decrease in plasma fibrinogen concentration was noted during the aortic clamping in non-heparinized animals. Morphological studies of lung tissue revealed numerous fibrin/platelet thrombi, leukocyte and platelet aggregates, atelectases and bleedings. In homogenized lung tissue, areas with elevated radioactivity were found, indicating fibrin/platelet entrapment. No such changes were seen in pigs pretreated with heparin. It was found that pulmonary microembolism occurs frequently after aortic clamping if heparin is not given at an early stage of the procedure.

Animals↗