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Biomedical subjects

H Oxlund

Publications and source records attributed to H Oxlund.

At least 91 records · Page 5Linked to original sources

Biochemical studies of normal and keratoconus corneas.

Keratoconus corneas are characterized by a reduced mechanical stability. The mechanical strength depends primarily on the collagen. In the present study the cross-linking pattern is analysed because it is important for the mechanical properties; an analysis of the amino acids of the collagen is included. Surprisingly, we did not find any change in the cross-linking pattern of collagen from keratoconus corneas compared to normal corneas. Neither did we find any difference in the composition of amino acids of the collagens. Thus no alteration was found in the molecular structure which could explain the marked reduction in the mechanical stability of keratoconus corneas.

Adolescent↗

Effect of D-penicillamine on the mechanical properties of aorta, muscle tendon and skin in rats.

The biomechanical properties of rat aorta, muscle tendon and skin were studied after daily D-penicillamine treatment (500 mg/kg) for 5, 10 and 42 days. D-Penicillamine treatment for 5 days resulted in increased aortic extensibility. After long-term treatment the aorta exhibited a shift towards decreased extensibility and increased stiffness at small 'stress' values. Simultaneously the dry weight and diameter of the aortic samples were increased after D-penicillamine treatment for 42 days. After correction of the mechanical parameters for the increased amount of tissue of the samples, the stiffness at small 'stress' values was still increased and the mechanical stability at high 'stress' values retained. This is in contrast to the marked reduction in the strength of muscle tendon and skin of the same animals after D-penicillamine treatment for 42 days. This study demonstrates that a primary increase in the extensibility of aorta may elicit a reactive formation of vascular connective tissue. It is proposed that aortic smooth muscle cells are activated by an increased pulsatile distension of the vessel wall secondary to the early effect of D-penicillamine on collagen and elastin. The resulting excess deposition of collagen and elastin leads to increased stiffness, which may in turn increase the susceptibility of the aortic wall to hemodynamic injury. Consequently D-penicillamine may not as proposed counteract the development of atherosclerosis.

Animals↗

D-penicillamine-induced angiopathy in rats. Changes in aortic collagen, glycosaminoglycans, DNA and RNA in rats treated with D-penicillamine.

Male Sprague-Dawley rats were treated with D-penicillamine (D-pen) in doses of 100, 250 or 500 mg/kg per day for 10, 32, 42 or 70 days. In addition animals were examined 28 days after withdrawal from 42 day's treatment with D-pen at 100 or 500 mg/kg per day. Pair-fed rats served as controls. The changes in aortic collagen, glycosaminoglycans (GAGs), DNA and RNA were studied. D-Pen had a dose- and time-related solubilizing effect on aortic collagen, which regained normal resistance to extraction within 28 days after cessation of the treatment. In contrast, D-pen caused a progressive accumulation of hydroxyproline (Hyp) in the aortic wall during and after treatment, probably mediated by an increased number of matrix synthesizing cells, as judged by augmentation of the DNA content in the presence of unaltered Hyp/DNA and RNA/DNA ratios. The relative amount of type III collagen was increased after 500 mg/kg per day D-pen for 10 and 42 days. High doses of D-pen increased the percentage of water in the aortic wall and reduced the ratio of Hyp to total tissue protein, suggesting an increased content of water-binding substances. This was confirmed by GAG accumulation. Hyaluronic acid (HA) and chondroitin 4,6-sulphate (CHS) were predominant after 32 and 42 days, whereas CHS, heparan sulphate (HS) and dermatan sulphate (DS) prevailed after 70 days of treatment. These observations suggest that processes of repair and regeneration are elicited secondary to the inhibitory effect of D-pen on aortic collagen and elastin crosslinking. Hypertrophy of the vessel wall may imply an increased rigidity, resulting in further increase of the susceptibility to haemodynamic injury.

Animals↗

Changes in mechanical properties, thermal stability, reducible cross-links and glycosyl-lysines in rat skin induced by corticosteroid treatment.

The effects of systemic cortisol treatment on the biophysical and biochemical properties of skin were investigated. Rats were injected sc with cortisol for 14, 60 and 120 days and samples of lumbar skin were studied. Corticosteroids exert a biphasic effect on the strength of skin: 1) a relatively fast increase in the strength and stability, caused by an increased collagen cross-linking and 2) an inhibited collagen synthesis which ultimately results in a thinning of the skin and a decrease of collagen content consistent with clinical observations. The thermal stability is increased indicating an increased proportion of thermostable cross-links in skin collagen. No changes are observed in the percentage type III collagen with respect to type I collagen. Increased amounts of glucose attached to the epsilon-amino group of lysine residues in the collagen are found after long-term treatments, an alteration which may play a role in hampering the tissue functions.

Age Factors↗

Long term local cortisol treatment of tendons and the indirect effect on skin. An experimental study in rats.

The mechanical properties of muscle tendon after long term local cortisol treatment were studied as well as those of skin with regard to possible systemic effects. Rats received cortisol injections 10 mg/kg into each hind limb, around the peroneal tendons every third day for 55 days. A control group was injected in the same way, but with saline. The local cortisol treatment did not alter the mechanical properties of the peroneous longus tendon, even though its dry weight and hydroxyproline content was reduced. A systemic effect on skin from the dorsum was observed. The thickness and hydroxyproline content were reduced, and in spite of that, the strength of the skin specimens increased. The hydroxyproline/nitrogen ratio in purified, insoluble skin collagen was not changed after the cortisol treatment. Two different effects of corticosteroids on collagenous tissues are suggested to act here: (1) within the first one to two weeks corticosteroids induce a relatively fast increase in the stability of the collagenous tissue, (2) followed by a progressive thinning and reduction in collagen of the tissue, caused mainly by an inhibited collagen synthesis. Thus the strength of the muscle tendon is not reduced, even though its collagen content is reduced after local cortisol treatment for 55 days.

Animals↗

On fundamental and phenomenological models, structure and mechanical properties of collagen, elastin and glycosaminoglycan complexes.

This paper reviews the structure (from molecular to macroscopic level) of collagen, elastin and glycosaminoglycans, with special reference to their functional properties and to how their behavior can be elucidated from in vitro manipulations of the tissues by biochemical means. Modes to analyse the mechanical behavior are briefly discussed and exemplified by data from reconstituted collagenous "tissue". It is concluded that the basic equation for the "non-linear elasticity" component in Fung's law (and for the reconstituted "tissue" a modification of it) is a powerful tool for analysis of the physiological range of the stress-strain curve. Further, enzymatic "dissection" of one tissue element at a time provides a valuable method for the analysis of tissue element interactions. This approach is illustrated with data from aortic tissue. It is shown that the mechanical properties of the aorta depend on the interaction between elasticity and collagenous elements and that the strength of the tissue is not derived from its collagen fibers per se.

Animals↗

The biochemical properties of tendon and skin as influenced by long term glucocorticoid treatment and food restriction.

The influence of long term systemic glucocorticoid treatment and food restriction on the mechanical properties of muscle tendons and skin was investigated. A group of male, albino rabbits received prednisolone intramuscularly for 63 days. Another group was food restricted to achieve the same weight loss as the prednisolone treated group. The untreated control group had free access to food and water. Peroneus tertius and longus tendons and strip specimens of lumbal skin were tested in a materials testing machine. Long term prednisolone treatment reduced the dry weights of the muscle tendons, with no change in collagen content and "stress"-strain parameters. The elastic stiffness measured after exhaustion of the viscosity in the tendons was found to be increased. The collagen content of skin was reduced, which resulted in a weakening of the skin as such. However, the extensibility of the skin strips was reduced and the maximum "stress" value, i.e. load value normalized to collagen content, was increased. The food restriction did not change the mechanical properties of muscle tendons. For skin the collagen content was reduced and so were the maximum load and "stress" values after food restriction. It is concluded that both long term glucocorticoid treatment and food restriction reduce the amount of collagen and strength of skin, consistent with clinical experiences. However, in long term glucocorticoid treatment the remaining collagen has increased stability, probably caused by a changed cross-linking pattern, in contrast to a reduced stability of skin collagen in food restriction. Skin is thus influenced more easily than muscle tendon.

Animals↗

Biomechanical changes in connective tissues induced by experimental diabetes.

The biomechanical properties of skin and aorta were studied in rats with experimental (streptozotocin) diabetes. After 30 days of diabetes the collagen content of the skin was diminished by 30%. By biomechanical testing collagen from diabetic rats was found to exhibit increased stiffness and strength: maximal stiffness was increased by 20% and the strain at maximum stress was decreased by 10%. Insulin treatment prevented all changes. No differences were found between aortic specimens from diabetic and normal rats.

Animals↗

Changes in the biomechanical properties of skin and aorta induced by corticotrophin treatment.

The work presented here is an investigation of the effect of elevated levels of corticosteroids on the biophysical properties of skin, aorta and muscle tendon. Rats were given corticotrophin injections for 10, 30 and 60 days to elevate the level of plasma endogenous corticosteroids. The corticotrophin treatments did not change the water or collagen content of specimens from dorsal skin, thoracic aorta and peroneal muscle tendons, tested mechanically. Changes became evident after longer treatment times. For both skin and aorta, the tensile strength, elastic stiffness and failure energy were increased after 60 days of treatment. The corticotrophin treatment did not influence the mechanical properties of muscle tendons. Complete reversibility of changes in the mechanical properties induced by 30 days of corticotrophin treatment was found after an additional period of 30 days of saline injections. This study indicates that an increased level of plasma corticosteroids elicited by corticotrophin treatment may increase the stiffness of the connective tissue of the organism. In the aorta this results in loss of capacitive function with increased haemodynamic strain on the aortic wall.

Adrenocorticotropic Hormone↗

The influence of adrenalectomy on the biomechanical properties of collagenous structures of rats in the post-partum phase.

Pregnancy influences the functional properties of both genital and extragenital connective tissues. The sex hormones induce a major part of these changes but also corticosteroids may play a role, as their concentration is elevated during pregnancy and early post-partum. The biomechanical properties of the pubic symphysis, muscle tendon and skin of intact and adrenalectomized rats during the first ten days of the post-partum phase were investigated. For the pubic symphysis and the muscle tendon of the intact animals there was a decrease of the stiffness in the early post-partum phase followed by a restoration. For the adrenalectomized animals there was no such initial decrease, which indicates that relaxation during pregnancy has been less pronounced. However, the strength of muscle tendons from the adrenalectomized animals was markedly decreased during the post-partum phase. The stiffness of the skin from the intact animals was increased in the early post-partum period. The increase was also found in adrenalectomized animals, but here the strength and stiffness were not only restored to the intact level but became further reduced during the post-partum period. It seems therefore that the adrenal glands not only participate in the development of adaptive changes during pregnancy, but also play a role in the stabilization of extragenital connective tissues in the post-partum phase.

Adrenal Glands↗

The influence of a local injection of cortisol on the mechanical properties of tendons and ligaments and the indirect effect on skin.

The effects of local cortisol treatment on the mechanical properties of muscle tendon and ligament in rats were studied. In addition to the local effects, possible systemic effects as reflected in the properties of the skin, remote from the site of the injection, were investigated. Two groups of rats were given cortisol injections, 20 mg/kg, every third day for 24 days. In one of the groups the injections were given bilaterally around the peroneal tendons and in the other they were given into both knee joint cavities. Specimens from the peroneal tendons, the posterior cruciate ligament with bone attachments, and strips of skin from the dorsum, were tested in a materials testing machine. The local treatment resulted in increased "tensile strength" of the peroneus brevis tendon and increased maximum load and stiffness of the peroneus longus tendon with no change in the collagen content in any of the samples. The posterior cruciate ligament always broke at one of the two sites of attachment to the bone and the maximum load value at these points was decreased after local cortisol treatment. The systemic effects of this local cortisol treatment on the skin were decreased thickness and fat content, increased collagen concentration and higher "tensile strength" and failure energy. From this study it is concluded that local cortisol injections for 24 days increase the strength and stiffness of muscle tendons, but decrease the strength of the bone attachments of ligaments. This treatment also results in a systemic effect which shows itself as increased strength of the skin remote from the site of the injections.

Animals↗

The roles of hyaluronic acid, collagen and elastin in the mechanical properties of connective tissues.

Biomechanical testing of connective tissue is usually done on whole tissue. Studies of the mechanical properties of each component of the tissue, however, are important for elucidating the connection between the functional properties and the molecular structure. Enzymic degradation of one component at a time followed by mechanical testing was employed. The specificity of enzymes used was ascertained with mechanical tests on collagen films from purified, reconstituted collagen after enzymic treatment. The study shows that collagen is the component which is mainly responsible for the tensile strength of skin and aorta, while the toe-part of the 'stress'-strain curve of aorta is determined by both elastin and collagen. The hyaluronic acid does not seem to play any role in the static mechanical properties of skin and aorta as evaluated by means of the present method.

Animals↗

Seasonal variations in the biophysical properties of rabbit aorta and its susceptibility to arteriosclerosis.

The physiological variations in the mechanical properties of rabbit aortae in relation to the periods of hair shedding were studied. The load-strain curves of the eight proximal thoracic segment in 15 shedding and 15 non-shedding male albino rabbits were analysed. The slope of the curves (tangent of the angle between the linear region of the load-strain curve and the strain axis) was decreased in the shedding animals compared to that of the non-shedding animals and the toe of the load-strain curves was significantly lower towards the x-axis in the shedding animals. The observations indicate a lower stiffness, that is increased elasticity, of the aortae of rabbits during hair shedding. The increased elasticity during hair shedding may explain the previously reported resistance to experimental arteriosclerosis caused by the hemodynamic strain elicited by exposure to systemic hypoxia. A decrease in the aortic content of collagen and of sulfated glycosaminoglycans, and an increase in the content of hyaluronic acid, may be of importance in the alterations of the mechanical properties of rabbit aorta during hair shedding.

Animals↗

The influence of cortisol on wound healing of the skin and distant connective tissue response.

The effect of moderate dosage cortisol treatment on healing wounds and on the response in skin distant to the wounds was investigated. The stress-strain characteristics of a skin wound and intact skin specimens were examined. Also, skin thickness, water content and collagen content were measured. Cortisol treatment resulted in reduced extensibility and increased stiffness for ten day wounds, but unchanged failure energies; for 20 day wounds, failure energies were reduced, indicating reduced ability to withstand rupturing forces. Thus, the mechanical properties of healing wounds under moderate dosage, long term corticosteroid treatment were found to be slightly impaired. A systemic effect of wounding at day 10 resulted in decreased stiffness and increased collagen content of the skin distant to the wound.

Animals↗