Although the precise etiology of low back pain is disputed, degeneration of the intervertebral disc is believed to play an important role. Many animal models have been described which reproduce the changes found in degenerative disc disease, but none allow for efficient, large-scale testing of purported therapeutic agents. The purpose of this study was to develop a simple animal model resembling degenerative disc disease using the intervertebral discs found in the tails of rats. The proximal two intervertebral discs in the tails of 20 rats were injected with either chondroitinase ABC or control (phosphate buffered saline, PBS). The tails were harvested at 2 weeks, and measurements were made of intervertebral disc height (measured radiographically and histologically), biomechanics (stiffness, hysteresis, and residual deformation), and histologic appearance. Treatment with chondroitinase ABC resulted in a significant loss in intervertebral disc height (radiographic intervertebral disc height, p = 0.001 ; histologic intervertebral disc height, p < 0.001) and significant increases in all biomechanical parameters (stiffness, p < 0.001; hysteresis, p = 0.006; residual deformation, p = 0.004) compared to PBS controls. Intervertebral discs treated with chondroitinase ABC had significantly lower histologic grades for each grading category (nucleus pulposus (NP), annulus fibrosus, and proteoglycan staining) compared to controls. The results of injury with chondroitinase ABC were similar to the findings in degenerative disc disease: reduced intervertebral disc height, diminished proteoglycan content, loss of N P cells, and increased stiffness of the disc. Thus, the model appears to be a reasonable tool for the preliminary in vivo evaluation of proposed treatments for degenerative disc disease.
Objective: To determine if blood levels of 25-hydroxyvitamin D (25-D) or its active metabolite, 1,25-dihydroxyvitamin D (1,25-D), are lower in women at the time of first diagnosis of breast cancer than in comparable women without breast cancer. Design: This was a clinic-based case-control study with controls frequency-matched to cases on race, age, clinic and month of blood drawing. Setting: University-based breast referral clinics. Subjects: One hundred and fifty-six women with histologically documented adenocarcinoma of the breast and 184 breast clinic controls. Results: There were significant mean differences in 1,25-D levels (pmol ml) between breast cancer cases and controls; white cases had lower 1,25-D levels than white controls (mean difference Ϯ SE: −11.08 Ϯ 0.76), and black cases had higher 1,25-D levels than black controls (mean difference Ϯ SE: 4.54 Ϯ 2.14), although the number of black women in the study was small. After adjustment for age, assay batch, month of blood draw, clinic and sample storage time, the odds ratio (95% confidence interval, CI) for lowest relative to highest quartile was 5.2 (95% CI 2.1, 12.8) for white cases and controls. The association in white women was stronger in women above the median age of 54 than in younger women, 4.7 (95% CI 2.1, 10.2) vs. 1.5 (95% CI 0.7, 3.0). There were no case-control differences in 25-D levels in either group. Conclusions: These data are consistent with a protective effect of 1,25-D for breast cancer in white women.
The kidneys are thought to be the only organs capable of 1 alpha-hydroxylation of vitamin D and its metabolites. We have examined the in vivo conversion of 3H-(25,26)-25-hydroxyvitamin D3(25OHD3) to 3H-(25,26)-1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] in vitamin D-deficient, pregnant and nonpregnant rats. As expected, nephrectomy of nonpregnant, vitamin D-deficient rats prevented the conversion of 25OHD3 to 1 alpha,25(OH)2D3. In contrast, nephrectomy of pregnant, vitamin D-deficient rats reduced but did not abolish the formation of 1 alpha,25(OH)2D3 from its precursor. The identity of the radioactive metabolite formed from 3H-25OHD3 which circulated in nephrectomized, pregnant rats was established as 1 alpha,25(OH)2D3 by comigration with synthetic 1 alpha,25(OH)2D3 on high-pressure liquid chromatography. The simultaneous absence of 1 alpha,25(OH)2D3 in the fetal kidneys indicated that the site of 1 alpha-hydroxylation after nephrectomy of the pregnant rat was probably extra-renal in origin. Two sites of 1 alpha-hydroxylation of 25OHD3, one renal and the other extra-renal, either fetoplacental or maternal, may exist in the pregnant, vitamin D-deficient rat.
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