Chem Res Toxicol. 2002 Sep;15(9):1174-8.
Evaluation of commercial ginkgo and echinacea dietary supplements for colchicine using liquid chromatography-tandem mass spectrometry.

Li W, Sun Y, Fitzloff JF, van Breemen RB.

Department of Medicinal Chemistry and Pharmacognosy, UIC/NIH Center for Botanical Dietary Supplements Research, College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612, USA.

In response to concerns that commercial dietary supplements containing Ginkgo biloba (ginkgo) and Echinacea purpurea, Echinacea angustifolia, or Echinacea pallida (echinacea) might be contaminated with colchicine, a highly selective and sensitive assay was developed for colchicine that is based on high-performance liquid chromatography-tandem mass spectrometry (LC-MS-MS). The method utilizes reversed-phase HPLC separation of compounds in a methanolic extract of the dietary supplement or botanical sample followed by positive ion electrospray ionization with collision-induced dissociation and multiple reaction monitoring of three characteristic fragmentation pathways of the protonated molecule of colchicine, m/z 400 --> 358, 400 --> 326, and 400 --> 310. The minimal detectable concentration of colchicine using this assay was 10 pg on-column, which is equivalent to 20 ppb colchicine in a 0.5 g ginkgo leaf sample. The method was validated by analyzing 0.5 g samples spiked with colchicine and determining the recovery. A total of 26 commercial ginkgo and echinacea dietary supplements were purchased from pharmacies in Chicago, IL, and analyzed for colchicine. In contrast to a recent report, no colchicine was detected in any of the samples. In addition, authenticated ginkgo leaves were collected, assayed, and found to contain no colchicine, which is consistent with the botanical literature. On the basis of the results obtained using this new LC-MS-MS assay, which is more sensitive and more selective than previously published methods for colchicine, we find no cause for concern regarding colchicine contamination of ginkgo or echinacea dietary supplements.


Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12230411&dopt=Abstract colchicine



J Cell Sci. 2002 Oct 1;115(Pt 19):3747-56.
Meiotic telomere clustering is inhibited by colchicine but does not require cytoplasmic microtubules.

Cowan CR, Cande WZ.

Department of Plant and Microbial Biology, University of California - Berkeley, Berkeley, CA 94720-3200, USA.

Telomere clustering, the defining feature of the bouquet, is an almost universal feature of meiotic prophase, yet its mechanism remains unknown. The microtubule-depolymerizing agent colchicine was found to inhibit bouquet formation. Telomeres in colchicine-treated cells remained scattered in the nuclear periphery, whereas untreated cells exhibited a prominent telomere cluster. Colchicine administered after the bouquet had formed did not affect telomere dispersal. The effect of colchicine on bouquet formation appeared to be separable from its effect on cytoplasmic microtubules; amiprophos methyl, a highly effective plant microtubule-depolymerizing drug, did not affect telomere clustering. Inhibition of bouquet formation was limited to colchicine and the related drug podophyllotoxin out of the variety of microtubule-depolymerizing drugs tested, suggesting that the target involved in bouquet formation has a structural specificity.


Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12235285&dopt=Abstract colchicine



Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13096-101. Epub 2002 Sep 16.
Topical colchicine selection of keratinocytes transduced with the multidrug resistance gene (MDR1) can sustain and enhance transgene expression in vivo.

Pfutzner W, Terunuma A, Tock CL, Snead EK, Kolodka TM, Gottesman MM, Taichman L, Vogel JC.

Dermatology Branch, Building 10/Room 12N260, National Cancer Institute, National Institutes of Health, 10 Center Drive, MSC 1908, Bethesda, MD 20892-1908, USA.

For skin gene therapy, achieving prolonged high-level gene expression in a significant percentage of keratinocytes (KC) is difficult because we cannot selectively target KC stem cells. We now demonstrate that topical colchicine treatment can be used to select, in vivo, KC progenitor cells transduced with the multidrug resistance gene (MDR1). When human skin equivalents containing MDR1-transduced KC were grafted onto immunocompromised mice, topical colchicine treatments significantly increased (7-fold) the percentage of KC expressing MDR1, compared to vehicle-treated controls, for up to 24 wk. Topical colchicine treatment also significantly enhanced the amount of MDR1 protein expressed in individual KC. Furthermore, quantitative real-time PCR analysis of MDR1 transgene copy number demonstrates that topical colchicine treatment selects and enriches for KC progenitor cells in the skin that contain and express MDR1. For clinical skin gene therapy applications, this in vivo selection approach promises to enhance both the duration and expression level of a desired therapeutic gene in KC, by linking its expression to the MDR1 selectable marker gene.


Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12235361&dopt=Abstract colchicine



Clin Exp Rheumatol. 2002 Jul-Aug;20(4 Suppl 26):S13-6.
Colchicine neuromyopathy: a report of six cases.

Altiparmak MR, Pamuk ON, Pamuk GE, Hamuryudan V, Ataman R, Serdengecti K.

Department of Nephrology, Cerrahpasa Medical School, University of Istanbul, Turkey. gepamuahoo.com

Colchicine has been in use for therapeutic purposes for many years. It can, however, cause subacute onset muscle and peripheral nerve toxicity in patients with chronic renal failure. In this report we describe 6 patients who developed neuromyopathy after the administration of colchicine. All patients presented with proximal muscle weakness, elevated serum creatine kinase (CK) levels, and neuropathy and/or myopathy on electromyography (EMG). The diagnosis of colchicine toxicity was confirmed in all cases by the normalization of CK levels and EMG after discontinuation of the drug. Toxicity developed in 4 renal failure patients on therapeutic doses of the drug, while one patient took a massive dose for suicidal reasons, and the other was on high-dose therapy. Patients using colchicine--especially those with renal failure--should be warned about the side effects of the drug and physicians should be careful in the administration of the drug.


Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12371628&dopt=Abstract colchicine