[Altered collagene characteristics and lysyl oxidase activity in lathyrism].

Experiments were carried out on rats with lathyrism, which was induced by adding semicarbazide (0.075%) into drinking water for 45 days. The data obtained show a 30% reduction in the body weight and an increase in.organ weight coefficients. Semicarbazide intake led to the pelvic limb paralysis, scoliosis, bone tissue degradation, cartilage growth, 46% decrease of the calcium level in the femur. It has been detected essential structural changes in extracellular matrix based on the collagen cross-links reduction. The activity of lysyl oxidase, a key enzyme for the collagen development, showed 5-fold decrease in the aorta tissues. The level of formaldehyde, a nonenzymic cross-links developer, has been measured in the liver tissue by the aldehyde trap (5,5-dimethyleyclohexane-1,3-dione) administration and then fluorimetric determination of formaldimedone. Under semicarbazide load, the formaldehyde level in the liver tissue was reduced by 47%. Therefore, semicarbazide influences not only the enzymic development of aldehyde groups in collagen, but the level of other aldehydes, which can cause cross-links. This experimental model of lathyrism is appropriate for investigation of the lysyl oxidase inhibitors effect on extracellular matrix.

Mechanical properties of fast and slow skeletal muscle with special reference to collagen and endurance training.

The mechanical properties of the slow soleus and the fast rectus femoris muscle under passive stretching were studied in endurance trained, untrained and lathyritic rats, aged 3 months. The soleus muscle with more abundant and cross-linked collagen had higher ultimate tensile strength and tangent modulus compared to the fast rectus femoris muscle which, on the other hand, had higher maximum strain. The inhibition of collagen cross-linking by lathyrism resulted in decreased tensile strength and stiffness, especially in the soleus muscle, whereas endurance training showed the opposite effects. It is supposed that the properties of collagen partly explain the capacity of slow muscles to maintain posture and to perform prolonged dynamic work. The effects of training on the tensile properties further indicate the close relationship between intramuscular collagen and the endurance capacity of muscles.

Collagenase activity of cartilage in rats with experimental lathyrism: a model of bone diseases.

Collagenolytic activity was estimated in skin and joint cartilage of lathyritic rats by means of a biological assay. Lathyrism was induced by feeding beta-aminopropionitrile fumarate for six weeks, and the lathyritic state was confirmed by characteristic radiographic, histomorphologic and biochemical findings. Both tissues in lathyritic animals revealed significantly increased collagenolytic activity in comparison with those of the control animals. Studies were performed using ethylendiaminetetraactate and normal rat serum to determine the origin of inhibition of the collagenolytic system inhibition. Since both agents showed no inhibition of collagenolysis, the highly increased collagenolytic activity in lathyritic skin and joint cartilage appears not to be derived from polymorphonuclear cells nor from serum, but from the tissue itself. Elevation of collagenase activity may be important with respect to the increased neutral salt solubility of collagen and hydroxyproline excretion observed in experimental lathyrism.

Intrinsic enzyme activity associated with tropoelastin.

The presence of an enzyme(s) associated with purified tropoelastin has been established. Results indicate that the enzyme(s) remains closely associated with the soluble elastin throughout the entire purification procedure suggesting that it is very tightly bound. Enzymatic activity is optimum through the pH range 7-9 (37 degrees C) and can be inhibited by disodium ethylenediaminetetraacetate, N-ethylmaleimide, sulfite, soybean trypsin inhibitor and human alpha-1-antitrypsin. The fragmentation pattern appears to be specific and reproducible.

[LDH- and MDH-isoenzymes in the costo-chondral junction in experimental lathyrismus and under additional medication with 6-methyl-prednisolone and O-(beta-hydroxyethyl)-rutosides]. / LDH- und MDH-Isoenzyme in der Knorpel-Knochengrenze der Rippen beim experimentellen Lathyrismus und unter zusätzlicher Medikation von 6-Methyl-Prednisolon und O-(beta-Hydroxyaethyl)-Rutosiden

Several classic studies suggest that experimental lathyrism is not only based on an extracellular distrubance of collagen fibre maturation but on a disturbed cellular energy metabolism. To exemplity this in assessment of skeletal damage the isoenzymes of LDH and MDH on the bone metabolism have been determined. Thus in experimental lathyrism the capacity for glycolysis and for oxidative energy production are significantly diminished in the rib bones and rib cartilage. The resulting reduction of glycoseaminoglycans in the ground substance, thus disturbing the function of the matrix in the formation of collagen fibres. In the bone the lack of mature collagen fibres leads to a mineralisation disturbance because of impaired nucleation function. Thus experimental lathyrism cannot be regarded as a disturbed extracellular collagen metabolism. "Venoruton" could not correct the lathyrogenic disturbance of energy metabolism, but after 3 weeks 6-methyl-prednisolone caused a normalisation of the state of energy metabolism.