Multivariated variance analysis applied to biological experiments: An analysis with curves of rats teeth growth as influenced by colchicine

The evaluation of the growth of incisor teeth of rats as influenced by colchicine (doses of 25, 50, 100 and 200 μg/kg) injected during 10 and 18 days is performed using a multivariated variance analysis, which allowed a global view of the results, showing that: there are differences in the growth of teeth of control group (untreated rats) and those treated with colchicine, in the measurements made at the 4th, 7th and 10th days of experiment); there is no difference in the growth of the teeth between the groups treated during 10 and 18 days, except in the measurements made at the 7th day; there is no influence of the doses of colchicine in the group treated during 10 days and in the group treated during 18 days - only at the 7th day is observed an influence of the doses used; and there was no significant interaction between treatment and days of measurement, showing the similarity of the groups during the experiment.

Autoradiographic investigation of effects of high-dose colchicine on dentinogenesis in rat incisors

Twelve female Wistar rats received 1.5 mg/kg of colchicine (CLC) intravenously. Control animals were similarly injected with isotonic saline solution. The animals were killed 5 h, 24 h, 3 days and 7 days after injection. Ninety minutes prior to sacrifice, all animals received an intraperitoneal injection of 3H-proline. Autoradiograms of maxillary incisors showed that CLC increased the retention of the labeled precursor in the odontoblasts. It was also shown that the odontoblasts in the different sectors of the rat incisor present different sensitivities to the CLC action.

A method for chromosome preparations from large fish specimens using in vitro short-term treatment with colchicine

This paper describes a new technique for preparing mitotic fish chromosomes using short-term in vitro treatment with colchicine. The results show that a large number of good quality metaphases (many suitable for chromosome banding) can be obtained by this technique, which requires an average of 1 h and 30 min for all steps. The procedure considerably reduces the time normally required for chromosome preparations in fish.

Direct effects of colchicine on myocardial function: studies in hypertrophied and failing spontaneously hypertensive rats

The aging spontaneously hypertensive rat (SHR) is a model in which the transition from chronic stable left ventricular hypertrophy to overt heart failure can be observed. Although the mechanisms for impaired function in hypertrophied and failing cardiac muscle from the SHR have been studied, none accounts fully for the myocardial contractile abnormalities. The cardiac cytoskeleton has been implicated as a possible cause for myocardial dysfunction. If an increase in microtubules contributes to dysfunction, then myocardial microtubule disruption by colchicine should promote an improvement in cardiac performance. We studied the active and passive properties of isolated left ventricular papillary muscles from 18- to 24-month-old SHR with evidence of heart failure (SHR-F, n=6), age-matched SHR without heart failure (SHR-NF, n=6), and age-matched normotensive Wistar-Kyoto rats (WKY, n=5). Mechanical parameters were analyzed before and up to 90 minutes after the addition of colchicine (10(-5), 10(-4), and 10(-3) mol/L). In the baseline state, active tension (AT) developed by papillary muscles from the WKY group was greater than for SHR-NF and SHR-F groups (WKY 5.69+/-1.47 g/mm2 [mean+/-SD], SHR-NF 3.41+/-1.05, SHR-F 2.87+/-0.26; SHR-NF and SHR-F P<0.05 versus WKY rats). The passive stiffness was greater in SHR-F than in the WKY and SHR-NF groups (central segment exponential stiffness constant, Kcs: SHR-F 70+/-25, SHR-NF 44+/-17, WKY 41+/-13 [mean+/-SD]; SHR-F P<0.05 versus SHR-NF and WKY rats). AT did not improve after 10, 20, and 30 minutes of exposure to colchicine (10(-5), 10(-4), and 10(-3) mol/L) in any group. In the SHR-F group, AT and passive stiffness did not change after 30 to 90 minutes of colchicine exposure (10(-4) mol/L). In summary, the data in this study fail to demonstrate improvement of intrinsic muscle function in SHR with heart failure after colchicine. Thus, in the SHR there is no evidence that colchicine-induced cardiac microtubular depolymerization affects the active or passive properties of hypertrophied or failing left ventricular myocardium.

Effect of Colchicine on Myocardial Injury Induced by Trypanosoma cruzi in Experimental Chagas Disease

Background: The hallmark of Chagas disease (CD) is multifocal myocarditis and extensive fibrosis. We investigated the potential effect of colchicine on myocardial remodeling in experimental CD. Methods and Results: One hundred Syrian hamsters were randomly divided into noninfected untreated control (CG), noninfected control treated with colchicine (COLG 0.4 mg kg(-1) d(-1) by gavage), infected (IG), and infected treated with colchicine (ICOLG, 0.4 mg kg(-1) d(-1)) groups. The interstitial collagen volume fraction (ICVF) was evaluated by videomorphometry with picrosirius red staining. The gelatinolytic activities of matrix metalloproteinase (MMP) 2 were examined with the use of zymography. Myocarditis was described according to the Dallas criteria. Statistical comparisons were performed with parametric analysis of variance and Tukey test. ICVF (%) accumulation was attenuated in infected colchicine-treated animals in the left (CG 0.81 +/- 0.13, COLG 0.85 +/- 0.13, IG: 1.35 +/- 0.31,* ICOLG 1.06 +/- 0.19; *P < .05 compared with ICOLG) and right ventricles (CG 1.4 +/- 0.36, COLG 1.26 +/- 0.14, IG 1.97 +/- 0.058,* ICOLG: 1.52 +/- 0.23; *P < .05 compared with ICOLG). A significant increase in MMP-2 enzymatic activity (UA) was observed in ICOLG (17,432.8*) compared with GC (3731.6), COLG (2,792.6), and IG (4,286.3; *P < .001). In IG, 66% of animals had myocarditis compared with only 49% in ICOLG. Conclusions: Colchicine had a protective effect on myocardium, indicated by decreased interstitial myocardial fibrosis, increased intensity of MMP-2, and attenuated myocardial inflammation. (J Cardiac Fail 2012;18:654-659)

[In Medea's gardens--two tales of colchicine]

Colchicine is a highly active alkaloid used in the treatment of acute inflammatory syndromes such as Mediterranean fever, M. Behçet or gouty arthritis. The two cases we present here illustrate exemplarily the pros and contras of colchicine therapy. In the first case, colchicine was successfully given for recurrent febrile attacks due to acute rheumatic fever. The second patient unfortunately had a fatal colchicine intoxication. The pharmacology of colchicine, the clinical features associated with overdose and the options for treatment are discussed. Colchicine should not be given in combination with macrolides, especially in patients with renal insufficiency.

Effect of colchicine and amiprophos-methyl on the production of in vitro doubled haploid onion plants and correlation assessment between ploidy level and stomatal size

Doubled haploid onion (Allium cepa L.) plants allow the production of completely homozygous lines for a later production of hybrids. The haploid plants are normally produced using in vitro gynogenesis. The obtained haploid plantlets must be treated with different agents for doubling chromosomes. It is necessary to adjust the concentration and the length of treatment of the doubling agent. In this case, the effect of 250 and 500 mg.L-1 colchicine and 15.2; 30 and 60 mg.L- 1 amiprophos-methyl during 24 and 48 h was assessed over the rate of onion haploid plantlets chromosome doubling. The best duplication treatment was 250 mg.L-1 colchicine for 48 h, which yielded 100% of doubled haploid plants. On the other hand, a positive correlation resulted from the ploidy level and stomatal size, and a negative correlation between the level of ploidy and stomatal density. Significant differences between the stomatal length, width and density in haploid and doubled haploid plantlets were observed. An economical and quick method to test ploidy level in onion plantlets is proposed through the measurement of stomatal size and density.

Colchicine in agriculture, medicine, biology, and chemistry

Includes bibliographies.

The biology of breast tumor progression : acquisition of hormone independence and resistance to cytotoxic drugs

Many breast tumors appear to follow a predictable clinical pattern, being initially responsive to endocrine therapy and to cytotoxic chemotherapy but ultimately exhibiting a phenotype resistant to both modalities. Using the MCF-7 human breast cancer cell line as an example of an 'early' phenotype (estrogen and progesterone receptor positive, steroid responsive, low metastatic potential), we have isolated and characterized a series of hormone-independent but hormone-responsive variants (MIII and MCF7/LCC1). However, these variants remain responsive to both antiestrogens and cytotoxic drugs (methotrexate and colchicine). MIII and MCF7/LCCl cells appear to mimic some of the critical aspects of the early progression to a more aggressive phenotype. An examination of the phenotype of these cells suggests that some hormone-independent breast cancer cells are derived from hormone-dependent parental cells. The development of a hormone-independent phenotype can arise independently of acquisition of a cytotoxic drug resistant phenotype.

Microtubulin binding sites as target for developing anticancer agents

Microtubules (MTs) play important and diverse roles in eukaryotic cells. Their function and biophysical properties have made α−and β−tubulin, the main components of MTs, the subject of intense study. Interfering with normal MT dynamics, for example, by the addition of tubulin ligands, can cause the cell great distress and affect MT stability and functions, including mitosis, cell motion and intracellular organelle transport. It has been shown in the literature that tubulin is an important target molecule for developing anticancer drugs. Tubulin binding molecules have generated considerable interest after the successful introduction of the taxanes into clinical oncology and the widespread use of the vinca alkaloids vincristine and vinblastine. These compounds inhibit cell mitosis by binding to the protein tubulin in the mitotic spindle and preventing polymerization into the MTs. This mode of action is also shared with other natural agents eg colchicine and podophyllotoxin. However various tubulin isotypes have shown resistance to taxanes and other MT agents. Therefore, there is a strong need to design and develop new natural analogs as antimitotic agents to interact with tubulin at sites different from those of vinca alkaloids and taxanes. This minireview provides SAR on several classes of antimitotic agents reported in the literature. The structures and data given are essential to the scientists who are involved in drug design and development in the field of anticancer drugs.

Novel ANKH amino terminus mutation (Pro5Ser) associated with early-onset calcium pyrophosphate disease with associated phosphaturia

This report describes a 32-year-old woman presenting since childhood with progressive calcium pyrophosphate disease (CPPD), characterized by severe arthropathy and chondrocalcinosis involving multiple peripheral joints and intervertebral disks. Because ANKH mutations have been previously described in familial CPPD, the proband's DNA was assessed at this locus by direct sequencing of promoter and coding regions and revealed 3 sequence variants in ANKH. Sequences of exon 1 revealed a novel isolated nonsynonymous mutation (c.13 C>T), altering amino acid in codon 5 from proline to serine (CCG>TCG). Sequencing of parental DNA revealed an identical mutation in the proband's father but not the mother. Subsequent clinical evaluation demonstrated extensive chondrocalcinosis and degenerative arthropathy in the proband's father. In summary, we report a novel mutation, not previously described, in ANKH exon 1, wherein serine replaces proline, in a case of early-onset severe CPPD associated with metabolic abnormalities, with similar findings in the proband's father.

Tubulin synthesis and auxin-induced root initiation in phaseolus

The auxin-induced formation of roots in the hypocotyls of Phaseolus vulgaris can be prevented by treatment with actinomycin D, colchicine or cytochalasin B if applied within 40 hr of initiation. Shortly after auxin pretreatment, there is an increase in translatable messenger RNA activity. Analysis of the labelled cell-free products indicate, among other changes, a striking increase in a protein co-migrating with tubulin, in the case of RNA isolated from indolebutyric acid (IBA) pretreated hypocotyls. An increase in tubulin content in vivo can also be demonstrated on the basis of SDS-polyacrylamide gel analysis of membrane proteins and functional assays for tubulin polymerization. An increase in the synthesis of tubulin in vivo can also be demonstrated after IBA pretreatment. In addition, the auxin is also able to promote tubulin polymerization when added in vitro. It is suggested that tubulin synthesis and microtubule assembly are early events in auxin-mediated root differentiation.