The effects of cyclophosphamide were studied 2, 5 and 9 days after terminating a two-week every-second-day intraperitoneal medication in young, male rats. The cytostatic effect was assessed by counting white blood cells (WBC) in arterial blood. WBC counts were reduced by 72% of control values at 2 days and regained normal values at 9 days after an overshooting leucocytosis at 5 days. Compared to control animals, the treated rats had significantly reduced body weights, metaphyseal bending strength and longitudinal growth of the femur at all time intervals observed. The torsional strength of the femur diaphysis and the strength of wounded skin were not affected at 2 days, but significantly reduced at 5 and 9 days. The tensile strength of intact skin was not found to be affected by the drug. From the 5th to the 9th day after ending medication, the curves for control and treated animals were assuming parallel slopes regarding metaphyseal bone strength, longitudinal bone growth and tensile strength of wounds. This may indicate reversion of the drug effects approximately one week after terminating medication.

No abstract

The metabolism of collagen and mineral was studied during a nine‐day postmedicational period in young, male rats receiving high‐dose intraperitoneal cyclophosphamide treatment every second day for 12 days. Two days after ending medication the white blood cell counts (WBC) were reduced by about 70%. Both synthesis and solubility of collagen were suppressed by the present medication 2 days after termination of treatment. This suppression continued throughout the 9‐day postmedicational period in bones, whereas in connective tissue of porous, ceramic implants both total collagen and the amount of salt soluble collagen regained normal values 9 days after cessation of treatment. Increased mineralization was found 2 days after ending medication and this high degree of mineralization persisted during the postmedicational period studied. Serum albumin levels were reduced and no increases were detected during the postmedicational period. The suggestion is made that the general protein synthesis is affected by high‐dose cyclophosphamide administration.

I . Mechanical properties and hydroxyproline content of connective tissue in porous ceramic implants. Acta path. microbiol. sand. Sect. A. 87: 193-200. 1979.'The present study describes a model applying ceramic implants (A 1203) for iri i ' i i~ studies of connective tissue regeneration. Two types of implants have been developed: a one-piece model for histological examination and chemical analyses. and a two-piece implant which can also be used for mechanical testing of connective tissue. When these were implanted subcutaneously on the back of rats. a correlation was found between the mechanical strength and the hydroxyproline content of connective tissue in the implants. The peak synthesis occurred between the 7th and the 14th day after implantation, and a plateau was reached for both strength-increases and hydroxyproline-formation between the 14th and the 2lst days. For histological examination. the implants were embedded in plastic materials and prepared as hard tissue specimens. The model presented can be applied to study connective tissue regeneration in normal and pathological conditions. including studies of the effects of various drugs on connective tissue.

The effects of low (5 mg/kg × 7) and high (20 or 30 mg/kg × 7) doses of cyclophosphamide on the formation an solubility of collagen in subcutaneous, porous implants, bones and incisional skin wounds were studied in young, male rats. At the 5 mg/kg schedule, effects from the drug were only detected as an increased solubility of collagen in implant connective tissue. At the 20 mg/kg schedule, there was a significant reduction of the synthesis and solubility of collagen in bones and in skin wounds. The 30 mg/kg schedule significantly depressed all the parameters studied except the specific activity of hydroxyproline in implants. Collagen stability seems to be impaired at low dose levels, whereas one of the main effects of high doses appears to be inhibition of collagen synthesis.