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Titolo:
A combination of subtherapeutic doses of chemically modified doxycycline (CMT-8) and a bisphosphonate (clodronate) inhibits bone loss in the ovariectomized rat: A dynamic histomorphometric and gene expression study
Autore:
Ramamurthy, NS; Bain, S; Liang, CT; Barnes, J; Llavaneras, A; Liu, Y; Puerner, D; Strachan, MJ; Golub, LM;
Indirizzi:
SUNY Stony Brook, Sch Dent Med, Stony Brook, NY 11794 USA SUNY Stony Brook Stony Brook NY USA 11794 Med, Stony Brook, NY 11794 USA Skeletech Inc, Kirkland, WA USA Skeletech Inc Kirkland WA USASkeletech Inc, Kirkland, WA USA Cent Univ Venezuela, Caracas, Venezuela Cent Univ Venezuela Caracas Venezuela niv Venezuela, Caracas, Venezuela NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA NIA Baltimore MD USA 21224NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA Natl Hlth Res Inst, Taipei, Taiwan Natl Hlth Res Inst Taipei TaiwanNatl Hlth Res Inst, Taipei, Taiwan
Titolo Testata:
CURRENT MEDICINAL CHEMISTRY
fascicolo: 3, volume: 8, anno: 2001,
pagine: 295 - 303
SICI:
0929-8673(200102)8:3<295:ACOSDO>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
MODIFIED NONANTIMICROBIAL TETRACYCLINE; PERIODONTAL-DISEASES; PARATHYROID-HORMONE; INDUCED OSTEOPENIA; TRABECULAR BONE; CORTICAL BONE; GROWING RATS; AGED RATS; ESTROGEN; APOPTOSIS;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Ramamurthy, NS SUNY Stony Brook, Sch Dent Med, Stony Brook, NY 11794 USA SUNY Stony Brook Stony Brook NY USA 11794 ok, NY 11794 USA
Citazione:
N.S. Ramamurthy et al., "A combination of subtherapeutic doses of chemically modified doxycycline (CMT-8) and a bisphosphonate (clodronate) inhibits bone loss in the ovariectomized rat: A dynamic histomorphometric and gene expression study", CURR MED CH, 8(3), 2001, pp. 295-303

Abstract

Recent studies have demonstrated that tetracyclines can reduce bone loss in the ovariectomized (OVX) rat model of osteoporosis. In the current study,a non-antimicrobial, chemically modified doxycycline (CMT-8), alone or in combination with a bisphosphonate (Clodronate), was evaluated in this model. Forty-two, 6month old. female rats were randomly assigned to the following groups, (6/ group): a) sham/vehicle, b) OVX/vehicle; c) OVX/1 mg/day CMT-8; d) OVX/2 mg/day CMT-8, e) OVX/1 mg/week Clodronate; and f) OVX/1 mg/day CMT-8 + 1 mg/week Clodronate, CMT-8 was administered by oral gavage, Clodronate injected S/C. Following sham surgery or OVX, the rats were treated for90 days with CMT-8 or vehicle alone, injected at three different times with fluorochrome labels, the rats were sacrificed, and the tibiae excised foranalysis by dynamic bone histomorphometry. Femurs were aseptically removedand analyzed for collagen, collagenase and osteopontin mRNAs by Northern and dot blot analysis. As expected, OVX decreased trabecular bone volume (BV/TV by 73.8% vs. sham p<.01), and also reduced trabecular thickness, numbers, and increased spacing. Done loss in the OVX animals was partially prevented with either 2 mg/day CMT-8 or 1 mg/wk Clodronate (p<.01), while the mg/day CMT-8 had no effect. Interestingly, the efficacy of the combination therapy of CMT-8 and Clodronate was significantly better than either treatmentby itself; maintaining bone mass and structural indices at levels identical to sham values. OVX rats mRNA for collagen, collagenase and osteopontin were elevated indicating high-turnover bone loss. Only COMBO therapy significantly reduced the collagenase and osteopontin mRNA. In summary, CMT-8 mono-therapy (2 mg) alone partially inhibited bone loss in this animal model ofosteoporosis. However, 1mgday (CMT-8) monotherapy had no effect on bone loss or bone mRNA levels and when combined with Clodronate, interacted to increase efficacy. Thus, a combination of a suboptimal dose of CMT-8 and a bisphosphonate appears to increase the amount of bone by suppressing resorption in a model of osteoporosis.

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Documento generato il 05/04/20 alle ore 22:56:56