Neurosurgery. 2003 Feb;52(2):381-7; discussion 387.
Intraneural colchicine inhibition of adenoviral and adeno-associated viral vector remote spinal cord gene delivery.

Boulis NM, Willmarth NE, Song DK, Feldman EL, Imperiale MJ.

Department of Neurosurgery, The Cleveland Clinic Foundation, Lerner Research Institute, Cleveland, Ohio 44195, USA. bouliscf.org

OBJECTIVE: The mechanism of remote viral gene delivery to the spinal cord is unknown. The present experiment demonstrates that intraneural injection of colchicine is capable of inhibiting remote delivery of both adenoviral and adeno-associated viral (AAV) vectors, implicating axonal transport in this process. METHODS: The right sciatic nerves of adult Sprague-Dawley rats were injected with phosphate-buffered saline (PBS) (n = 5) or 10 (n = 7) or 100 (n = 4) microg colchicine. Two days later, the nerves of all animals were initially injected with 1.2 x 10(7) plaque-forming units of Ad5RSVntLac-Z. Two separate groups were injected concurrently with vector and PBS (n = 5) or 10 microg colchicine (n = 5). In a second experiment, the right sciatic nerves of CD1 mice were preinjected with PBS (n = 6) or 10 microg colchicine (n = 5). Two days later, the nerves were injected with rAAVCAG-EGFPwpre (an adeno-associated vector carrying the green fluorescent protein gene). In both experiments, sciatic nerves and spinal cords were removed and analyzed for gene expression. RESULTS: Sciatic nerve vector injection resulted in expression in both the nerve injection site and neuronal cell bodies located predominantly in the ipsilateral ventral horn. Analysis of variance revealed a significant treatment effect for 10 and 100 microg intraneural colchicine with inhibition of remote adenoviral delivery at 10 microg and blockade of remote delivery at 100 microg (P < 0.001). Colchicine injection concurrent with and before vector injection had similar inhibitory effects. Two-way analysis of variance revealed significant colchicine inhibition of remote delivery in both adenovirus- and AAV-injected animals (P < 0.003) but no dose-by-vector interaction, suggesting that both vectors are equally inhibited by colchicine. CONCLUSION: Colchicine inhibits remote spinal cord delivery of adeno-associated and adenoviral vectors in a dose-dependent manner, suggesting that remote delivery is dependent on retrograde axonal transport.


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Eur J Pediatr. 2000 Dec;159(12):895-7.
Near fatal acute colchicine intoxication in a child. A case report.

Goldbart A, Press J, Sofer S, Kapelushnik J.

Paediatric Department B, Soroka University Medical Centre, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

An 8-year-old child with familial Mediterranean fever exhibited signs of colchicine intoxication while receiving prophylactic doses of the drug. She developed gastrointestinal, central nervous system, cardiovascular and haematological disturbances. Over 2 months she had been drinking high doses of natural grapefruit juice which, combined with long-term colchicine therapy and a viral upper respiratory tract infection, increased her susceptibility to the drug. CONCLUSION: To the best of our knowledge, this is the first time colchicine intoxication in this age group has been described in the English literature.


Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11131346&dopt=Abstract colchicine



Acta Univ Palacki Olomuc Fac Med. 2000;143:47-50.
Effect of colchicine and its derivatives on the expression of selected isoforms of cytochrome P450 in primary cultures of human hepatocytes.

Dvorak Z, Ulrichova J, Modriansky M, Maurel P.

Institute of Medical Chemistry and Biochemistry, Medical Faculty, Palacky University Olomouc, Hnevotinska 3, 77515 Olomouc, Czech Republic.

The study addressed the effect of colchicine and its derivatives on the protein levels of cytochrome P450 (CYP) 1A2, 2A6, 3A4, 2C9/19, and 2E1 isoforms. Primary human hepatocyte culture was the model of choice. Levels of individual CYP isoforms were detected using immunoblotting. Colchicine caused an increase of CYP2E1 protein content, colchiceine and N-deacetylcolchiceine induced isoforms CYP2C9, 2E1 and 3A4 whereas colchicoside induced CYP2C9 and 2E1. The levels of CYP1A2 and 2A6 were unaffected by any of tested compounds. Demecolcine and 3-demethylcolchicine had no effect on any studied P450 isoform. Since colchicine is an exclusive substrate of CYP3A4 whereas it induces CYP2E1, there is a suspicion rather at protein stabilization than at gene induction concerning induction origin.


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Cell Tissue Res. 2000 Dec;302(3):391-5.
Induction of apoptosis by colchicine in taste bud and epithelial cells of the mouse circumvallate papillae.

Takeda M, Suzuki Y, Obara N, Nagai Y.

Department of Anatomy, School of Dentistry, Health Sciences University of Hokkaido, Tobetsu, Ishikari, Hokkaido 061-0293, Japan. matakedoku-iryo-u.ac.jp

Apoptotic cells in the taste buds and epithelia of mouse circumvallate papillae after colchicine treatment were examined by the methods of in situ DNA nick-end labeling, immunocytochemistry, and electron microscopy. After colchicine treatment, numerous positive cells appeared in the taste buds by DNA nick-end labeling, and some epithelial cells in the basal and suprabasal layers in and around the circumvallate papillae also revealed positive staining. Condensed and fragmented nuclei with a high density were occasionally found in the taste bud cells and in the basal and suprabasal layer epithelial cells by electron-microscopic observation. An immunocytochemical reaction for tubulin revealed weak staining in taste bud cells, because of the depolymerization of microtubules, and a decrease of the microtubules in the taste bud cells was observed by electron microscopy. These results indicate that colchicine treatment of mice induces the apoptosis of taste bud and epithelial cells in the circumvallate papillae and dorsal epithelial cells around the circumvallate papillae.


Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11151451&dopt=Abstract colchicine