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  • 1
    Electronic Resource
    Electronic Resource
    Effect of clodronate on established collagen-induced arthritis in rats (1995)
    Springer
    Inflammation research 44 (1995), S. 258-263 
    Details
    ISSN: 1420-908X
    Keywords: Collagen-induced arthritis ; Clodronate ; Inflammation ; Histology ; Biochemical variables
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The collagen-induced arthritis model in rats was used to study the effect of disodium clodronate on inflammation and destruction of tarsal, metatarsal, and interphalangeal bones and joints. Female DA rats were immunized with heterologous type II collagen. Fourteen days after immunization, rats with similar scores were assigned to the different experimental groups. They were treated subcutaneously either with saline (controls) or with clodronate at doses of 12.5 and 25 mg/kg/day five times a week for 2 weeks. Clinical signs of arthritis including the severity of paw swelling were assessed weekly. At the time of killing, histological features of the non-decalcified tarsus with tarsal, tarsometatarsal and interphalangeal joints were assessed for inflammatory soft-tissue, articular, and bone changes. All the arthritic control rats developed severe arthritis as shown by the total histological scores of the hindpaw. The treatment with clodronate (25 mg/kg) decreased clinical signs of arthritis, the activity of the collagen-degrading lysosomal enzyme,β-N-acetylglucosaminidase, in inflamed hindpaw tissue, serum osteocalcin level and serum cross-linked telopeptide of type I collagen level. Histological evaluation indicated moderate arthritis in 29% of the rats and severe arthritis in 71%. The results show that clodronate given therapeutically to arthritic rats, induced with type II collagen, suppresses the intensity of inflammation and bone lesions in the tibiotarsal and tarsometatarsal regions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01782979
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  • 2
    Electronic Resource
    Electronic Resource
    A comparison of clodronate and indomethacin in the treatment of adjuvant arthritis (1997)
    Springer
    Inflammation research 46 (1997), S. 79-85 
    Details
    ISSN: 1420-908X
    Keywords: Key words: Adjuvant arthritis — Clodronate — Indomethacin — Inflammation — Histopathology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Objective and Design: The therapeutic effects of an anti-resorptive agent, clodronate, were compared with the effects of an anti-inflammatory agent, indomethacin, in rat adjuvant arthritis after therapy and after a follow-up time of two weeks. ¶Subjects: Eighty-one male Lewis rats, 6–7 weeks old, were immunized with heat-killed mycobacteria. ¶Treatment: Fourteen days after immunization the animals were treated either with clodronate (50 mg/kg/day, subcutaneously), indomethacin (3 mg/kg/day, orally) or saline (controls) for two weeks. ¶Methods: Clinical signs of arthritis including the severity of paw swelling were assessed, biochemical variables were mea-sured, and histological features of the non-decalcified tarsus with ankle, intertarsal and tarsometatarsal joints were evaluated for inflammatory soft-tissue, articular, and bone changes. ¶Results: The results indicated that clodronate and indomethacin suppressed significantly the intensity of inflammation, activity of 〈beta〉-N-acetylglucosaminidase in inflamed hindpaw tissue, serum ICTP (cross-linked carboxyterminal telopeptide of type I collagen) level and bone lesions in the tibiotarsal region. The level of serum osteocalcin was also significantly decreased by clodronate. The inhibitory effect of clodronate against arthritic bone changes occurred, however, earlier and was slightly more potent than the effect of indomethacin, while indomethacin was slightly more effective in reducing paw swelling. Both drugs preserved their therapeutic effects during the follow-up time of two weeks. ¶Conclusions: Clodronate and indomethacin have fairly similar efficacy in suppressing the intensity of joint swelling and preventing bone lesions in adjuvant arthritic rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s000110050093
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  • 3
    Electronic Resource
    Electronic Resource
    Biliary excretion of diazepam and its metabolites in man after repeated oral doses (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 209-212 
    Details
    ISSN: 1432-1041
    Keywords: Diazepam ; diazepam metabolites ; conjugates ; biliary excretion ; renal excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The concentration of free and conjugated diazepam, of its major demethylated metabolite, N-demethyldiazepam, and of its hydroxylated metabolites, N-methyloxazepam and oxazepam, were measured by a GLC-method in plasma, bile and urine following four nightly doses of diazepam 10 mg. Ten patients with a T-tube in the common bile duct after choledochotomy (Group I) were studied and 12 patients after cholecystectomy (Group II). Twelve hours after drug administration, the mean total concentration of diazepam in bile was 1/23 that in plasma. Similarly, during 9–10 h only low concentrations of diazepam were found in the urine, and in both urine and bile only the unconjugated drug was found. The principal metabolite of diazepam in plasma was N-demethyldiazepam. In bile an average of 77% of the total amount of N-demethyldiazepam was in the conjugated form, and its total concentration was half that in plasma. In urine N-demethyldiazepam was mainly in the conjugated form. No hydroxylated metabolites of diazepam were found in plasma. Oxazepam was the metabolite found in bile and urine in the next highest concentration after N-demethyldiazepam. In the urine it was mainly conjugated, but in bile only a mean of 35% was conjugated. Both in bile and urine, N-methyloxazepam was found only intermittently and in low concentration. Diazepam and all of its common metabolites were measured in human bile, and the concentrations found were too low to produce a clinically significant enterohepatic circulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609863
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  • 4
    Electronic Resource
    Electronic Resource
    Challenging models of elastic collisions with a computer simulation
    Amsterdam : Elsevier
    Computers and Education 20 (1993), S. 1-9 
    Details
    ISSN: 0360-1315
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Education
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0360-1315(93)90065-Q
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  • 5
    Electronic Resource
    Electronic Resource
    Clodronate Prevents Bone Loss in Aged Ovariectomized Rats (1997)
    Springer
    Calcified tissue international 61 (1997), S. 151 -157 
    Details
    ISSN: 1432-0827
    Keywords: Key words: Osteopenia — Aged rat — Clodronate — Histomorphometry — Biomechanics.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract. The purpose of this study was to investigate the ability of clodronate to prevent ovariectomy (OVX)-induced osteopenia in aged rats. Fourteen-month-old female Sprague-Dawley rats (n = 166) were randomized into six groups. One group was sacrificed at the start of the study, four groups were ovariectomized, and one group was sham-operated (Sham). The OVX rats were given subcutaneously either vehicle (veh) or clodronate at doses of 3, 7, or 25 mg/kg once a week for 3 months, and the Sham rats were given the vehicle. At all dose levels clodronate inhibited trabecular bone loss in the distal femur and in the fourth lumbar vertebral body (L4), and decreased bone resorption as evidenced by urinary deoxypyridinoline excretion. The lowest dose of clodronate preserved serum osteocalcin and endosteal bone formation of secondary spongiosa in L4 at the level of the Sham/veh group. The OVX-induced increase in periosteal bone formation of femoral diaphysis was unaffected by two smaller doses of clodronate, but was decreased to the level of Sham rats after the highest dose. After 3 mg/kg clodronate, the percentage of femoral cortical bone area and the mean relative cortical thickness were higher compared with the OVX/veh group. There was a good positive correlation between the maximum load in three-point bending of the tibia and tibial ash weight. Normal lamellar pattern of newly formed cancellous and cortical bone was found after clodronate treatment. No signs of adverse accumulation of osteoid or any deleterious effect on mechanical strength of long bones and lumbar vertebrae were found.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002239900314
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  • 6
    Electronic Resource
    Electronic Resource
    Effect of clodronate on established adjuvant arthritis (1994)
    Springer
    Rheumatology international 14 (1994), S. 139-147 
    Details
    ISSN: 1437-160X
    Keywords: Adjuvant arthritis ; Clodronate ; Inflammation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The rat adjuvant arthritis model was used to study the effect of disodium clodronate on inflammation and destruction of tarsal bones and joints. Male Lewis rats were given an intradermal injection of mycobacteria. Fourteen days after immunization, rats with similar scores were assigned to the different experimental groups. They were treated subcutaneously either with saline (controls) or with clodronate at doses of 12.5 and 25 mg/kg/day five times a week for 2 weeks. Clinical signs of arthritis including the severity of paw swelling were assessed weekly. At the time of sacrifice, histological features of the non-decalcified tarsus with ankle, intertarsal and tarsometatarsal joints were assessed for inflammatory soft-tissue, articular and bone changes. The total histological score of the hindpaw indicated that 58% of the control rats developed moderate arthritis and 42%, severe arthritis. The treatment with clodronate (25 mg/kg) decreased clinical signs of arthritis and the activity of the collagen-degrading lysosomal enzyme, β-N-acetylglu-cosaminidase, in inflamed hindpaw tissue. Histological evaluation indicated moderate arthritis in 83%, but no severe arthritis. The lower dose of clodronate also decreased the severity of the disease; the decrease was, however, statistically insignificant. The results show that clodronate given therapeutically to adjuvant arthritic rats suppresses the intensity of the inflammation and prevents secondary articular and bone lesions in the tibiotarsal region.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00579699
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