[Potential influence of nutrition with supplements on healthy and arthritic joints. II. Nutritional quantity, supplements, contamination]. / Potentielle Einflüsse der Nahrung samt Zusatzstoffen auf gesunde und arthrotische Gelenke. II. Nahrungsquantität, Zusatzstoffe, Kontaminationen.

A short period of fasting leads, in the mouse, to usually reversible damage to chondrocytes and in patients with rheumatoid arthritis often to a temporary improvement. Slight hypo-alimentation and a low-caloric diet reduce the spontaneous development of osteo-arthritis in the mouse, whereas a high-caloric diet promotes the disease. In man, mice, and, in particular, fattened animals, obesity is often associated with forms of osteo-arthritis. In such cases, it may be assumed that metabolic damage to cartilage is involved as well as damage due to weight-bearing forces. Elderly people, i.e., persons with a predisposition to osteo-arthritis, often suffer from a generalized vitamin deficiency. Vitamins E, B2, and C have been shown to exert an inhibitory effect on osteo-arthritis in animals, and it has been found that supplementation therapy, particularly with vitamin E and the combination of vitamins B1, B6, and B12, can exert a beneficial effect on the symptomatology of human degenerative joint disease. Mineral deficits in calcium, zinc and selenium (Kashin-Beck disease; endemic osteo-arthritis deformans) can provoke skeletal damage in humans and animals. On the other hand, calcium, iron, and copper have been reported to give rise to storage diseases, in some cases with involvement of articular cartilage. There have been indications that chondrotoxic damage may result from food contaminants. So far very little is known about the influence of phytopharmacodynamic substances (other than derivatives of rutin and rhein) on osteo-arthritis. The large gaps in our knowledge of the chondrotropic properties of the constituents of food and common stimulants underline the need for further investigations.

[Potential effects of nutrition including additives on healthy and arthrotic joints. I. Basic dietary constituents]. / Potentielle Einflüsse der Nahrung samt Zusatzstoffen auf gesunde und arthrotische Gelenke. I. Grundnahrungsstoffe.

Owing to the methodological difficulties involved, none of the studies so far published on the influence of diet on human osteo-arthritis has been fully comprehensive. We have therefore compiled a series of experimental observations--including some of our own--in the mouse and other species that have a bearing on this subject. Fats with a high content of saturated fatty acids, such as pork fat, greatly favored the development of spontaneous osteo-arthritis in the mouse, as also did cholesterol. Cottonseed oil and olive oil showed less tendency to do so. The highly unsaturated linoleic acid antagonized the effect of pork fat. Other vegetable oils and also fish oil exerted an anti-inflammatory and antinociceptive action in experimental animals. Foodstuffs rich in carbohydrates only promoted the development of degenerative joint disease in predisposed mice. Hyperglycemia (diabetes mellitus) constitutes a risk factor for the development of osteo-arthritis in humans as well as in mice and rats. A low-protein diet led to dysplasia of the hip joint in the dog; a high-protein diet inhibited the development of osteo-arthritis in the mouse, but promoted inflammation in volunteers. Disturbances of protein metabolism such as alkaptonuria can initiate degenerative processes in the joints of humans and animals.

[Effect of riboflavin (vitamin B2) on spontaneous gonarthrosis in the mouse]. / Einfluss von Riboflavin (Vitamin B2) auf die spontane Gonarthrose der Maus.

Male mice of the C57 black strain were given 1 mg/kg body weight of riboflavin (vitamin B2) in their drinking water daily for 4 months, in addition to the vitamin B2 contained in their standard pellet feed. Controls received the standard feed only. Histological examination of the joints at the end of the experiment showed that the incidence of gonarthrosis in the group given supplementary riboflavin was less than half that found in the controls; the number of mice with bilateral gonarthrosis was also considerably smaller, and the severity of the lesions less marked. Signs of physiological degeneration in the epiphyseal cartilage of the femoral and tibial condyles were only marginally less pronounced than in the controls. The notable inhibitory effect of riboflavin, which is known to promote regenerative processes, on osteoarthritis was compared with that of drugs stimulating wound healing, e.g. flavonoids, tribenoside, and zinc sulfate. These latter substances were also found to exert a similar inhibitory effect on spontaneous gonarthrosis in the mouse.

[Etiopathogenetic significance of bone changes in spontaneous gonarthritis in the mouse]. / Atiopathogenetische Bedeutung von Knochenveränderungen bei der spontanen Gonarthrose der Maus.

In the C57 Black, STR/IN and MAGf strains of mice, which are prone to develop spontaneous osteo-arthritis of the knee, histomorphological examinations were made of the osseous parts of the joint. It was found that the number of animals with osteo-arthritis and with degenerative changes in the epiphyseal growth zone increases with age. There is nevertheless evidently no interrelation between the two phenomena. The same applies to the occurrence of osteoporosis and degenerative joint disease, since male C57 Black mice, for example, develop osteo-arthritis of the knee relatively often, but develop osteoporosis much more rarely, while the opposite is observed in the females. Moreover, among the juvenile joint degenerations in the STR/IN and MAGf strains, a high percentage of osteo-arthritis of the knee is found, but only a few instances of osteoporosis. The majority of the (relatively rare) idiopathic condylar necroses coincide with osteo-arthritis of the knee, but not vice versa. The development of osteosclerosis and degenerative cartilaginous defects is mostly (possibly always) a sequela and not the cause of osteo-arthritis of the knee. Malpositions are often associated with the development of osteo-arthritis of the knee. The C57 Black strain exhibits a certain tendency to develop genu valgum, and the STR/IN strain almost regularly shows genu varum; no distinct tendency is detectable in MAGf mice. Like the osteophytes, the enlarged menisci with obligatory ossification centres invariably seen in conjunction with osteoarthritis apparently help to compensate for the condylar incongruence caused by the degenerative process, prevent partial dislocations, and hence improve the stability of the joint.

[Proliferative and metaplastic reactions as tentative reparatory processes in spontaneous arthritis in the mouse]. / Proliferative und metaplastische Reaktionen als tentative reparatorische Prozesse bei der spontanen Arthrose der Maus.

Performing histo-morphologic studies of knee joints in several hundred mice of the strains C57 black, STR/1N and MAGf, showing a disposition for spontaneous osteo-arthrosis, we found tentative reparative processes in many cases. There was a proliferation of cartilage and of the synovial membrane, mostly in the peripheral parts of the joints. The proliferating tissues were apparently moving towards an existing osteo-arthrotic focus. However, since cartilage and synovial tissues often became necrotic at the central, weight-bearing part of the joint they generally did not reach the defect. However, in a number of mice there were mostly small superficial defects in the joint cartilage filled with connective tissue of several grades of maturity. These regenerating spots were generally found in connection with the proliferating synovial membrane. In other animals there were fibrous vascularized pannus-like tissues, moving from the synovial membrane over the still normal cartilage towards a mostly centrally localized osteo-arthrotic ulcer. The pannus, like the inflammatory proliferating synovial membrane, often contained cartilaginous detritus. Attempts to regenerate arthrotic defects directly by local neoformation of cartilage, e.g. at the facies patellae of the femur, remained mostly without much success, showing only poor isles of chondrocytes, partially in cluster form. Interestingly, the menisci, like the synovial membrane, generally take part in the osteo-arthrotic process, also showing severe destructive alterations and rather often signs of regeneration, sometimes with cluster formation.

Effect of O-(beta-hydroxyethyl)-rutoside on wound healing in the rat.

The administration of O-(beta-hydroxyethyl)-rutoside in 11 daily doses of 300--400 mg/kg p.o. stimulates wound healing by granulation in the rat. The preparation may counteract the inhibitory effect of prednisone on the formation of granulation tissue. In five doses of 300--1,000 mg/kg daily p.o. it augments the tensile strength of cicatricial tissue to a statistically significant degree.

[Promoting and inhibitory influences of tribenoside and acetylsalicylic acid on spontaneous arthrosis in the mouse (author's transl)]. / Fördernde und hemmende Einflüsse von Tribenosid und Acetylsalicylsäure auf die spontane Arthrose der Maus.

Tribenoside administered in moderate doses over periods of three or ten months, inhibited the development of spontaneous arthrosis in mice of the C 57 black strain. Acetylsalicylic acid administered once daily in oral doses of 50 and 150 mg/kg for five months, had a distinctly promoting effect on the development of the same arthrosis. Attention is drawn to certain common features in the activity spectra of the two drugs, but especially also to their opposite effects on mucopolysaccharide metabolism and on regenerative processes which are promoted by tribenoside but inhibited by acetylsalicylic acid.

Effect of C 21 524-Su (pirprofen) on spontaneous osteoarthrosis in the mouse.

Mice of the C57 Black strain, aged 11-12 weeks, were treated once daily on 5 days a week for 4 months with C 21 524-Su (pirprofen) in doses of 10 and 30 mg/kg p.o. In this genetically predisposed strain of mice, increases in the incidence of gonarthrosis have been observed after the administration of certain anti-inflammatory agents such as acetylsalicylic acid. Radiography and in particular exact histological examination of the knee joints revealed, however, that neither the overall incidence nor the severity of osteoarthrosis was greater in the mice treated with C 21 524-Su than in the controls. On the contrary, in the treated animals there was a tendency for the incidence and the intensity of gonarthrosis to be lower.

[Preventive effect of tribenoside in spontaneous arthrosis of the mouse]. / Untersuchungen zur Frage einer prophylaktischen Wirkung von Tribenosid auf die spontane Arthrose der Maus

Tribenoside, a D-glucofuranose derivative, was administered prophylactically over a period of ten months to six-month-old mice of the C 57 Black strain (Animal Breeding Unit, Sisseln), which are known to have a predisposition to spontaneous gonarthrosis. The preparation was given once daily for five consecutive days every other week in doses of 100 or 300 mg/kg p.o. At the end of the treatment period, serial sections of both knee joints were examined. In the placebo-treated controls, arthrotic lesions of varying severity were found in 97% of the specimens. In the animals given tribenoside in either dosage arthrotic lesions were significantly less frequent and less severe. The number of animals with bilateral gonarthrosis and of those with proliferative changes was also significantly or highly significantly smaller in the groups treated with tribenoside than in the controls. The only indication of a dose-related effect of the preparation was the fact that arthrosis of the most severe grade was present in fewer animals in the group treated with the higher dose. At present, the mechanism of action responsible for the protective effect of tribenoside demonstrated once again in these experiments cannot be clearly defined.

[Influence of tribenoside on spontaneous osteoarthrosis in mice (author's transl)]. / Einfluss von Tribenosid auf die spontane Arthrose der Maus

1. In 15- to 21-month-old male mice of the C 57 black strain that had been treated with a placebo (olive oil), the incidence of gonarthrosis was found to be 19% in the youngest and 61% in the older animals. If the very early stages are included, the incidences range from 36% to 65%. 2. Only the most severe degrees of arthrosis could be diagnosed radiographically; mild stages were only detectable by histological examination under the light-microscope. 3. The motility of the older animals severely affected with arthrosis (as measured by reference to their ability to run over a grid) was for the most part limited. 4. The percentage of mice with gonarthrosis was diminished by treatment with ethyl-3,5,6-tri-O-benzyl-D-glucofuranoside (tribenoside, Glyvenol) in doses of 150, 500 or 1200 mg/kg p.o. weekly over a period of three months. Comparison of the animals that had received tribenoside with those given the placebo (olive oil) revealed that the incidence of lesions was 36-60% less in the former. If the very early stages of arthrosis were included in the evaluation, the differences were statistically significant (P less than 0.05) at the two higher dose-levels. 5. Under the given experimental conditions, no clear-cut dose-effect relation on the part of tribenoside was demonstrable, since the youngest animals with the least marked arthrosis were treated with the smallest dose of the preparation and the older animals, in which the incidence of arthrosis was higher, with the larger doses.

Suitability of the C57 black mouse as an experimental animal for the study of skeletal changes due to ageing, with special reference to osteo-arthrosis and its response to tribenoside.

Histological studies in male C57 black mice revealed a high incidence (39-61%) of osteo-arthrotic changes in the knee joint from about the 17th month of life. In animals of the same strain aged 15 1/2 months the incidence was only 19%. The incidence of gonarthroses in 16-month-old female mice was considerably lower (4%). In male mice aged 17-20 months, the oral administration of tribenoside in doses of 500 and 1,200 mg/kg weekly led to a significant (p less than 0.05) reduction in the overall arthrotic involvement. A possible relation between the effect of tribenoside and other anti-inflammatory agents on osteo-arthroses in the mouse and their influence on mucopolysaccharide metabolism in connective tissue is discussed. The incidence of the formation of gaps in the epiphyseal growth zones and of osteoporosis of the femur and tibia in the same strain increases distinctly with advancing age. Except in animals treated with the highest dosage tested, in which there was a significant decrease in the development of osteoporosis, tribenoside in the range of doses used had no influence on these skeletal changes.

Regeneration-promoting properties of tribenoside in Amblystoma mexicanum.

Tribenoside in a dose of 100 mg/kg i.p. significantly accelerates the regeneration of puncture wounds in the caudal membrane of Amblystoma mexicanum. A dose of 200 mg/kg exerts a less-pronounced vulnerary effect and is occasionally toxic. Tribenoside also stimulates regeneration in this species when added to bath fluid in a concentration of 1:400,000 (exposure for 6 h daily). A concentration of 1:200,000 is less effective and has a slightly irritant effect on the tissue. 14 days after operation, the rate of mitosis in the regenerative blastema is distinctly greater than that demonstrable in the normal integument of the axolotl. The number of cell divisions in the regenerating tissue is not significantly altered by tribenoside in a concentration of 1:400,000. The possible involvement of other mechanisms in the stimulated regeneration observed after treatment with tribenoside is discussed.

Cross-polarized target signature measurements.

Cross-polarized laser scattering cross sections were measured for twenty-four different paint samples as a function of scattering angle at four visible krypton laser frequencies. The relative magnitudes of the measured cross sections at the four frequencies were used to define a multispectral signature vector for each paint sample. Measured data confirmed the theoretical prediction that the direction of the cross-polarized multispectral signature vector is independent of the scattering geometry.