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PubMed2003

Antiannexin V autoantibody in thrombophilic Behçet's disease.

We propose that thrombosis in Behçet's syndrome may be due to disruption of the annexin V shield by antiphospholipid antibodies. Measurement of antiannexin V antibodies may be of value in confirming diagnosis and evaluating the risk of venous and arterial thrombosis in patients with Behçet's syndrome. To evaluate the efficiency of antiannexin V antibody in the formation of thrombosis, 53 male patients with Behçet's disease according to international study group criteria were involved in this study. The age range was 20-28 years (mean 23+/-3.4). All of these patients had been taking colchicum. Those taking medications that interfere with antiannexin V autoantibody levels were excluded, and serum samples were taken during the active period. Group I included 26 Behçet's patients with well-documented thrombosis, group II included 27 Behçet's patients without thrombosis, and group III was comprised of 27 healthy controls. There were no statistical differences between the mean concentrations of IgG and IgM antiannexin V autoantibodies in the three groups. The results indicate that these antibodies may not be associated with the pathogenesis of thrombotic events in patients with Behçet's syndrome.

Adult↗
PubMedDate not supplied

Colchicine poisoning.

Colchicine poisoning is an unusual but serious form of drug intoxication. Although relatively uncommon, colchicine poisoning may produce life-threatening systemic effects that must be recognized and treated by the emergency physician. This alkaloid found in Colchicum autumnale is used primarily in the treatment of gout. In toxic doses it produces nausea and vomiting, and bone marrow suppression often leading to sepsis, hypocalcemia, adult respiratory distress syndrome, and direct cardiotoxic effects. Treatment requires early recognition and supportive care including fluid and electrolyte replacement and occasionally blood component replacement therapy. Recent experiments using colchicine-specific antibodies have demonstrated beneficial effects on colchicine intoxication.

Colchicine↗
PubMed2004

Fast determination of colchicine by TLC-densitometry from pharmaceuticals and vegetal extracts.

Colchicine, (S)-N-(5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo-(a(-heptalen-7-yl)-acetamide, is the main alkaloid contained in Colchicum autumnale (meadow saffron). There are known colorimetric, spectrophotometric, volumetric, potentiometric, voltametric, gravimetric and various chromatographic methods for quantitative determination of colchicine, each of them presenting a series of advantages and disadvantages. As an alternative, we proposed the use of a densitometric determination for colchicine allowing the determination of this alkaloid from pharmaceutical products, as well from seeds of meadow saffron. The total alkaloid extract was separated by Thin-Layer Chromatography using Silicagel 60F(254) layers and a mixture of chloroform:acetone:diethylamine (5:4:1) as mobile phase. The same conditions were used for the determination from pharmaceutical products. Densitometric measurements were carried out at the absorption maximum (350 nm) of colchicine, the determinations being made by reflectance and by fluorescence. The peaks were optimized regarding to their area and shape by varying four scanning parameters (slit width and height, number of measurements and scanning speed). We established the calibration plot using pure colchicine in the range 50-600 ng mL(-1). The proposed method could be widely used in the pharmaceutical industry for the quick and accurate quantitative determination of colchicine because it eliminates the interferences given by other bioactive or degradation compounds. The method was characterized by validation parameters (linearity, accuracy, fidelity, sensitivity) and it was established its performances in comparison with an HPLC method and an official quantitative determination from the Romanian Pharmacopoeia X edition respectively.

Chromatography, Thin Layer↗
PubMed1998

Regulation of gelatinase B (MMP-9) in leukocytes by plant lectins.

The stimulatory or inhibitory effects of plant lectins on the production of gelatinase A (MMP-2) and gelatinase B (MMP-9) by mononuclear white blood cells was investigated by substrate zymography. Leukocyte cultures from 24-h old buffy coats were spontaneously activated and produced high levels of gelatinase B. Using such cultures the suppressing activity of the Datura stramonium, Viscum album, Bauhinia purpurea, Triticum aestivum and Maackia amurensis lectins on gelatinase B induction were demonstrated. When fresh leukocyte preparations from single blood donors were used, low levels of gelatinase B were produced. The induction of gelatinase B was confirmed for concanavalin A and phytohaemagglutinin (PHA-L4). In addition, the Urtica dioica, Calystegia sepium, Convolvulus arvensis and Colchicum autumnale lectins were documented as novel and potent inducers of gelatinase B. Since high circulating gelatinase B levels are associated with specific pathologies, including shock syndromes, the acute toxicity of many lectins might be partially mediated or influenced by gelatinase induction.

Cells, Cultured↗
PubMed2003

PFAPA syndrome mimicking familial Mediterranean fever: report of a Turkish child.

The PFAPA (Periodic Fever, Aphthous stomatitis, Pharyngitis, Adenitidis) syndrome is characterized by periodic fever, adenitis, pharyngitis, and aphthous stomatitis. Herein, we present a Turkish child with PFAPA syndrome mimicking familial Mediterranean fever because of a rare presentation. A 9-year-old boy was admitted with recurrent fever, aphthous stomatitis, sore throat, headache, and general body pains, lasting 2 to 3 days since 3.5 years of age. He was completely symptom-free between the attacks. He was diagnosed as having familial Mediterranean fever according to the clinical findings when he was 6 years of age and Colchicum tablet was administrated. Despite colchicines therapy for 8 months, his attacks did not subside; therefore, the drug was discontinued. He had high fever, a painful cervical lymphadenopathy, aphthous stomatitis, and tonsillo-pharyngitis. The patient was then diagnosed as having PFAPA syndrome. He was given a single dose of prednisolone (0.35 mg/kg/dose). His complaints dramatically and completely disappeared 3 h after administration of the drug. During the 8th month of follow-up, a similar febrile attack lasting only 1 day was noted and it was controlled with a single dose of prednisolone (0.5 mg/kg/day). At this writing the patient is in the 12th month of follow-up, and there have been no symptoms after the second attack. In conclusion, our patient shows that PFAPA syndrome can be confused with familial Mediterranean fever. We also would like to emphasize that the typical PFAPA syndrome can be easily diagnosed by detailed history-taking and physical findings.

Child↗
PubMed2005

Determination of colchicine residues in sheep serum and milk using high-performance liquid chromatography combined with electrospray ionization ion trap tandem mass spectrometry.

Colchicine is a naturally occurring alkaloid used in human and veterinary medicine. It shows genotoxicity in in vitro and in vivo systems even at low concentrations. Therefore, no ADI has been established, and colchicine has been included in Annex IV of Council Regulation (EEC) No. 2377/90. No abuse of this drug in intensive livestock farming has yet been reported. However, there may be a natural route of entry for this compound into the food chain when Colchicum autumnale is consumed by animals kept outdoors. To address this concern, we developed and validated a highly sensitive and selective quantitative LC-ESI-MS-MS method for the detection of colchicine in sheep serum and milk. For sample pretreatment, all samples were liquid-liquid extracted with phosphate buffer (pH 8.0) and dichloromethane. LC separation was carried out on an RP C18 column employing a 0.5% formic acid/acetonitrile gradient system. The recoveries in both matrixes at a concentration range from 0.0005 to 1 mg/L were >80% with RSDs of <10%. The applicability of the method was demonstrated in serum and the corresponding milk samples from Albanian sheep. After exposure to C. autumnale, the animals showed clinical signs of intoxication. Significant concentrations (up to 1 mg/L) of the drug were found in serum as well as in milk samples.

Animals↗
PubMed1990

Antitubulin effects of derivatives of 3-demethylthiocolchicine, methylthio ethers of natural colchicinoids, and thioketones derived from thiocolchicine. Comparison with colchicinoids.

Esterification of the phenolic group in 3-demethylthiocolchicine and exchange of the N-acetyl group with other N-acyl groups or a N-carbalkoxy group afforded many compounds which showed superior activity over the parent drug as inhibitors of tubulin polymerization and of the growth of L1210 murine leukemia cells in culture. A comparison of naturally occurring Colchicum alkaloids with thio isosters, obtained by replacing the OMe group at C(10) with a SCH3 group, showed the thio ethers to be invariably more potent in these assays. The comparison included 3-demethylthiodemecolcine prepared from 3-demethylthiocolchicine by partial synthesis. Thiation of thiocolchicine with Lawesson's reagent afforded novel thiotropolones which exhibited high antitubulin activity. Their structures are fully secured by spectral data. Colchicine and several of its analogues show good antitumor effect in mice infected with P388 lymphocytic leukemia, and all of them show high affinity for tubulin and inhibit tubulin polymerization at low concentration. Consequently, antitubulin assays with this class of compounds can serve as valuable prescreens for the initial evaluation of potential antitumor drugs.

Animals↗
PubMed1971

The melanocyte model. Colchicine-like effects of other antimitotic agents.

The effect of various agents that cause metaphase arrest in dividing cells was studied on the rapid reversible darkening of frog skin under the influence of melanocyte-stimulating hormone (MSH). Darkening is due to dispersion of melanin granules in melanocytes and is thought to be accompanied by a gel-to-sol cytoplasmic transformation. After subsequent washing the skin lightens, with aggregation of melanin granules and cytoplasmic gelation. As previously shown with colchicine, preincubation of frog skin with vinblastine, vincristine, or colcemid produced an increase in darkening induced by MSH, as compared to control skins, and a dosage-dependent inhibition of subsequent lightening. Preincubation with each drug, without subsequent MSH, produced a gradual, irreversible, dosage-dependent darkening over several hours. On a molar basis, the relative strength of the various agents was vinblastine > vincristine > colcemid > colchicine; vinblastine was about 100 times stronger than colchicine. Preincubation of frog skin with griseofulvin, followed by washing, had no subsequent effects on darkening or lightening. However, effects similar to those of the Colchicum and Vinca alkaloids were seen if griseofulvin was kept in the ambient media. These effects were rapidly reversible on removal of the drug from the media. These findings support the melanocyte model originally proposed for the action of colchicine, and emphasize certain facts that models of melanin granule movement will have to accommodate.

Animals↗
PubMed2002

Selective cytotoxicity evaluation in anticancer drug screening of fractionated plant extracts.

Chosen to reflect biodiversity in a phylogenetic sense, 100 fractionated plant extracts were screened in vitro for cytotoxicity following extraction and fractionation (polypeptide isolation). Of these 100 extracts, 30 were selected and then characterized preliminarily for antitumor potency and mode of action by testing them on two cell lines and primary cultures of human tumor cells. On the basis of cytotoxicity potency, 10 of the extracts were further characterized for anticancer activity in 10 human tumor cell lines. This final testing resulted in seven potential lead plants with superior evidence of antitumor potential: Colchicum autumnale L. (Colchicaceae), Digitalis lanata Ehrh. and Digitalis purpurea L. (Plantaginaceae), Helleborus cyclophyllus Boiss. (Ranunculaceae), Menyanthes trifoliata L. (Menyanthaceae), and Viola arvensis Murr. and Viola patrinii Ging. (Violaceae). Within a database of antitumor compounds, the activity profiles of the extracts from these seven plants were compared, by correlation analysis, with those of more than 100 other compounds, including 39 standard drugs from different classes of cytotoxic mechanisms. The activity profiles of six of these candidates were uncorrelated with those of the standard drugs, possibly indicating new pathways of drug-mediated cell death.

Antineoplastic Agents, Phytogenic↗
PubMed2006

A concise history of gout and hyperuricemia and their treatment.

First identified by the Egyptians in 2640 BC, podagra (acute gout occurring in the first metatarsophalangeal joint) was later recognized by Hippocrates in the fifth century BC, who referred to it as 'the unwalkable disease'. The term is derived from the Latin word gutta (or 'drop'), and referred to the prevailing medieval belief that an excess of one of the four 'humors'--which in equilibrium were thought to maintain health--would, under certain circumstances, 'drop' or flow into a joint, causing pain and inflammation. Throughout history, gout has been associated with rich foods and excessive alcohol consumption. Because it is clearly associated with a lifestyle that, at least in the past, could only be afforded by the affluent, gout has been referred to as the 'disease of kings'. Although there is evidence that colchicine, an alkaloid derived from the autumn crocus (Colchicum autumnale), was used as a powerful purgative in ancient Greece more than 2000 years ago, its first use as a selective and specific treatment for gout is attributed to the Byzantine Christian physician Alexander of Tralles in the sixth century AD. Uricosuric agents were first used at the end of the 19th century. In the modern era, nonsteroidal anti-inflammatory drugs are usually the drugs of choice for treating acute gout. Perhaps the most important historical advance in the treatment of hyperuricemia was the development of xanthine oxidase inhibitors, which are effective in reducing plasma and urinary urate levels and have been shown to reverse the development of tophaceous deposits.

Arthritis, Gouty↗
PubMedDate not supplied

[Recent plant poisoning in ruminants of northern and eastern Germany. Communication from the practice for the practice].

It is reported of botanical intoxications in 1379 ruminants (dairy cattle, beef cattle and ewes) in north-eastern Germany. The intoxications of these animals were caused by consumption of the following plants: meadow saffron (Colchicum autumnale L.), cowbane (Cicuta virosa L.), sweet clover (Melilotus alba MED.), sheep's sorrel (Rumex acetosella L.), bracken (Pteridium aquilinum KUHN) and St. John's wort (Hypericum perforatum L.). In all the five described cases animals died as a result of plant intoxications. The authors come to the conclusion that periodical inspections of the meadows are necessary, checking the plants in cooperation with veterinary surgeons.

Animals↗
PubMed2002

[Colchicine poisoning by accidental ingestion of the bulbs of Sandersonia aurantiaca: report of a case].

We report a case of colchicine poisoning in an 82-year-old woman. She had suffered from senile dementia and in her confused state ingested two bulbs of Sandersonia aurantiaca (Christmas-bells, Chinese lantern lily). She was admitted complaining of gastrointestinal symptoms, mainly severe watery diarrhea. The duration of her diarrhea was approximately 40 hours. On the 3rd day after ingestion, leukopenia and thrombocytopenia occurred. Although 50 micrograms of granulocyte-colony stimulating factor was administered from the 5th day to the 8th day, her white blood cell count did not increase and revealed nadir (100/microliter) on the 7th day. Her platelet count also revealed nadir on the 7th day. She died of respiratory failure in the early morning of the 9th day. The bulb of Sandersonia was found to contain colchicine at a concentration of 4.7 mg/g, and her serum level of colchicine was 6.3 ng/ml on the 6th day. Colchicine is an alkaroid extractable from the plants like Colchicum autumnale (meadow saffron, autumn crocus), and Gloriosa supra tuber. These plants belong to the lily family. Sandersonia aurantiaca also belongs to the lily family and we found that its bulb contained colchicine. To our knowledge, this is the first report of colchicine poisoning by Sandersonia aurantiaca.

Aged↗
PubMed1976

[The induction of chromosome loss and gain by colchicine (author's transl)].

The fruit fly Drosophila melanogaster is one of the standard systems used for mutagen screening. The colchicine-containing drugs Colchicum-Dispert and Colchysat Burger were fed at extremely low concentrations (1:300 000 and 1:50 000 respectively) to Drosophila females. Among their offspring a remarkably high frequency of aneuploid individuals (XO and XXY flies) were found. These aneuploids correspond karyotypically to the human Ullrich-Turner (XO) and Klinefelter's (XXY) syndromes and result from chromosome loss (XO) and chromosome gain (XXY). The maximum aneuploidy frequency observed after colchicine feeding was 24 times the control value. Depending on their size the aneuploidy frequencies are as great as those obtained by X-irradiation with some hundred or some thousand R.

Aneuploidy↗
PubMedDate not supplied

[Effect of alkaloids from celandine on calcium accumulation and oxidative phosphorylation in mitochondria depending on their DNA intercalating properties].

The effect of principal alkaloids (sanguinarine, chelerythrine, coptisine, chelidonine) of greater celandine Chelidonium majus L., as well as the alkaloids from Colchicum autumnale L. (colchicine and colchamine) on calcium accumulation and oxidative phosphorylation in rat liver mitochondria has been studied. The obtained data were compared with DNA intercalating properties of alkaloids detected by the method of thermodenaturation (DNA melting curve plots). It was found that chelerythrine and sanguinarine blocked absorption and accumulation of calcium cations and inhibited oxidative phosphorylation, while the coptisine significantly diminished those indices. Chelidonine, colchicines and colchamine had no influence on the studied characteristics. The effect of alkaloids upon mitochondria functional state correlated tightly with their DNA intercalating properties: chelerythrine and sanguinarine were strong intercalators, while coptisine was a weak one, and chelidonine, colchicine and colchamine did not interact with DNA and caused no changes in its melting point. Correlation coefficient between the intercalating properties of alkaloids and their inhibition of calcium accumulation was 0.89, and with their oxidative phosphorylation inhibition - 0.93. It is suggested that the effect of studied alkaloids upon functional properties of mitochondria can be mediated by mtDNA.

Alkaloids↗
PubMed1989

[The centennial of the discovery of the antimitotic properties of colchicine].

Pernice, a sicilian pathologist active mainly in Italy (Palermo) from 1884 to 1906, published one hundred years ago the first observation of the mitotic changes observed in two dogs injected with a large dose of tincture of Colchicum. His description of the considerable increase in mitotic figures in the gastric and intestinal mucosa, and the absence of ana-telophases, clearly illustrate the well-known effect of a spindle poison. They were however completely forgotten until 1949. The modern aspect of the action of colchicine on mitosis in relation with the properties of microtubules and their dynamic condition are briefly considered in relation with the history of colchicine in modern cell biology.

Animals↗
PubMed1982

Colchicine poisoning as a mode of suicide.

Two cases of suicide involving colchicine are examined. Colchicine and colchicum preparations have been used for the relief of pain in acute gout and are reported to be effective for the treatment of periodic peritonitis. A method using enzymatic digestion, extraction, and high pressure liquid chromatographic analysis for the extraction and analysis of colchicine in autopsy specimens is described.

Adult↗
PubMed1994

[Plant poisoning cases in Turkey].

In Turkey, the majority of the population live in rural areas where they use wild plants as food and medicine. The confusion of an edible plant with a poisonous one give rise to serious poisoning which may even result in death. The incidence of plant poisoning in Turkey is about 6% and especially high among children between ages of 2 and 11 living in rural areas. The number of species that cause poisoning is around twenty and Hyoscyamus niger (Solanaceae), Colchicum species (Liliaceae), Conium maculatum (Umbelliferae) and Prunus species (Rosaceae) are the most important. Mushroom poisoning is more frequent in spring and fall. The main reasons are their widespread usage as food and the inexperience of the gatherers in distinguishing the edibles from the poisonous. Amanita phalloides, A. verna, A. muscaria, A. pantherina are responsible for severe cases of poisoning.

Adult↗
PubMed1996

[Serious plant poisonings in Switzerland 1966-1994. Case analysis from the Swiss Toxicology Information Center].

AIM: To analyze the types, frequency and severity of plant poisonings in Switzerland over 29 years. METHODS: Retrospective analysis of severe poisonings with toxic plants reported to the Swiss Toxicological Information Center (STIC). Assessment of the causality, severity of symptoms and the types of plants involved. RESULTS: During the period under review the STIC registered 24 950 cases of contact with or ingestion of toxic plant material. In 99.4% of all cases the clinical course was either unknown, asymptomatic or associated with only minor symptoms (no hospitalization). Severe plant poisonings occurred in 152 cases. Detailed analysis was possible in 135 cases (23 children, 112 adults) including 5 lethal cases (all adults). The 24 plants involved produced the following severe symptoms: Atropa belladonna (42 cases): anticholinergic syndrome (42), acute psychosis (33), convulsions (2), coma (2). Heracleum mantegazzianum (18): severe photodermatitis (18). Datura stramonium (17): anticholinergic syndrome (17), psychosis (12), coma (2). Dieffenbachia (11): severe stomatitis (8), corneal lesions (3). Colchicum autumnala (10): diarrhea (10), liver necrosis (9), fatal multiorgan failure (2). Veratrum album (8): bradycardia ( < or = 40/min) (6), shock (5). Aconitum napellus (4): tachyarrhythmia (2), AV-block II/III (2). Aesculus hippocastanum (3): allergy (3), anaphylactic shock (2). Hyoscyamus niger (3): anticholinergic syndrome (3). Ricinus communis (3): diarrhea (3), toxic megacolon (1). Oenanthe crocata (2): convulsions (1), lethal coma (1). Taxus baccata (2): tachyarrhythmia (1), fatal asystole (1). Further single cases with severe poisonings were observed with Arum maculatum, Asarum europaeum, Chrysanthemum vulgare, Cyclamen persicum, Datura suaveolens, Glycyrrhiza glabra, Laburnum anagyroides, Lycopodium, Narcissus pseudonarcissus (lethal aspiration), Nerium oleander, Senecio vulgaris and Vicia faba. CONCLUSIONS: Potential and real intoxications with plant materials occurred in 7.2% of all cases registered at the STIC. However, among all plant cases only 0.6% were severe intoxications requiring hospitalization. Although severe plant intoxications are rare events, a small number of specific plants appear to be mainly responsible for continued serious plant poisoning in Switzerland. The present study has identified the plants with the highest toxicological risks and provides a data base for more rational prevention, diagnosis and treatment of plant poisoning cases in the future.

Adult↗