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At least 1,135 records · Page 63Linked to original sources
PubMed1997

Expression of nitric oxide synthase in hypothalamic nuclei following axonal injury or colchicine treatment.

Nitric oxide (NO) has recently gained much attention due to its apparently double-edged role in neuronal injury. This study was aimed at elucidating neuronal nitric oxide synthase (nNOS) expression in the brain after two types of injury, namely axonal transection and colchicine treatment. The neurosecretory hypothalamo-pituitary pathway served as a model for the reaction of central neurons to these two types of injury. Axonal transection, i.e., pituitary stalk section, resulted in a qualitative increase in NOS content in the supraoptic and paraventricular nuclei. In these nuclei, there was also an increase in the number of NOS-expressing neurons after the operation. Surprisingly, in the periventricular nucleus, a strong decrease in the number of NOS-positive magnocellular neurons was observed in the anterior part of the nucleus. Intracerebroventricular injection of colchicine resulted in an increase in the cell count in the paraventricular nucleus, while the other nuclei remained unchanged. Our results suggest that axonal injury results in an increase in nNOS expression in the major neurosecretory nuclei, while the periventricular nucleus shows the opposite reaction. Colchicine treatment has an effect similar to that of axotomy in the major neurosecretory nuclei, suggesting that an increase in NOS expression may be induced by interrupted axonal transport. In the periventricular nucleus, the decrease in the number of NOS-containing neurons suggests differences among hypothalamic NOS-containing neuron groups in response to neuronal injury.

Animals↗
PubMed1989

Effects of colchicine treatment on the cholinergic septohippocampal system.

The influence of hippocampal target cells on the septohippocampal cholinergic system was studied using immunocytochemical and autoradiographic procedures. The destruction of dentate granular cells by colchicine injection promotes a significant increase in the density of acetylcholinesterase staining and cholinergic-muscarinic receptors in the zone denervated by the terminal axons of granular cells, which supports the hypothesis of a proliferation of cholinergic fibers in CA3. In the septal region the number of choline acetyl transferase positive cells was significantly lower (by 23%) ipsilaterally to the colchicine injection as compared to the contralateral side; when the hippocampus is almost completely destroyed by colchicine treatment this cell loss is more important (by over 50%). The present results agree with those of earlier studies and suggest that target-derived trophic factors are important for the maintenance of the basal forebrain cholinergic system and that the fascia dentata provides a significant source of such factors.

Acetylcholine↗
PubMed1986

Effects of the new mitotic inhibitor pyrimidinsulfone NY 4137 on human cells in vitro and on colchicine binding to tubulin.

The effect of 2-(2-thenyl)sulfonyl-5-bromopyrimidine (NY 4137) on cells of the human line NHIK 3025 was investigated. It was shown that NY 4137 induces cell cycle specific inhibition in metaphase. A dose-dependent prolongation of metaphase was found and the fraction of cells able to escape metaphase arrest declined gradually as the concentration of NY 4137 increased. A total block in metaphase was achieved with 0.016 mM and higher concentrations of NY 4137. Interphase was also prolonged in cells treated with 0.016 mM. Inhibition of valine incorporation by NY 4137 was also found to be dose-dependent. Following a 2-h exposure to 0.2 mM NY 4137 valine incorporation was inhibited by 80-85%. Inhibition of colchicine and vincristine binding to purified tubulin was also investigated. Double reciprocal plot and gel filtration chromatography showed that NY 4137 competitively inhibited colchicine binding to DEAE-cellulose purified tubulin. NY 4137 had no effect on vincristine binding to tubulin. The binding of NY 4137 to tubulin at or near the colchicine binding site may be responsible for the metaphase arrest.

Binding Sites↗
PubMed1994

Pharmacokinetics and absolute bioavailability of colchicine after i.v. and oral administration in healthy human volunteers and elderly subjects.

The pharmacokinetics of colchicine were studied in six healthy male and four elderly female volunteers after i.v. and oral administration. Plasma samples were collected over 72 h and assayed for colchicine by a specific and sensitive radioimmunoassay. Plasma concentration-time curves were fitted using a three-compartmental model after i.v. administration of 0.5 mg (healthy volunteers) and 1 mg (elderly group) colchicine. The first distribution half-life (t1/2 lambda 1) was short: 9.2 min in healthy volunteers and 3.0 min in the elderly group; the second distribution half-life (t1/2 lambda 2) was of the same order for both groups, 1.2 h. Plasma elimination half-lives were also in the same range: 30 h for healthy volunteers versus 34 h for the elderly subjects. Mean residence time was also in the same range in the two groups: 27 h in healthy volunteers and 21 h for elderly subjects. The volume of distribution (Vz) was 6.7 l.kg-1 for the healthy group and 6.3 l.kg-1 for the elderly group, while Vss was smaller: 4.2 l.kg-1 for healthy volunteers and 2.9 l.kg-1 for elderly subjects. Total body clearance was 10.5 l.h-1 for healthy and 5.5 l.h-1 for elderly subjects. After oral administration of 1 mg, lag-time was 14 min in healthy volunteers and 11 min in elderly subjects. Maximal plasma concentration was 5.5 ng.ml-1 at 62 min in the healthy group, while in the elderly group Cmax was 12 ng.ml-1 at 87 min. Mean absolute bioavailability of the tablet was the same in both groups, 44% for healthy volunteers and 45% for elderly subjects.

Administration, Oral↗
PubMed1988

Fine-structural localization of neuropeptide tyrosine (NPY)-like immunoreactivity in the neuronal somata of colchicine-pretreated celiac ganglia of rats.

In colchicine-pretreated cells of sympathetic ganglia, intensely NPY-immunoreactive material was localized within vacuoles and vesicles of the disorganized, widely dispersed Golgi apparatus. Intensely positive large granular vesicles, which are known to be one of major storage sites of various peptides in the autonomic nerve endings, were essentially unobserved in the perikaryal cytoplasm. The present finding provides evidence that one pool of NPY-like immunoreactivity is localized in the Golgi apparatus of colchicine-pretreated as well as normal sympathetic ganglion cells. It is also clear that visualization of NPY-immunoreactive somata by colchicine-pretreatment in the sympathetic ganglia is due to the accumulation of the neuropeptide in the disorganized Golgi stacks instead of increased amount of the large granular vesicles containing NPY.

Animals↗
PubMed1984

Effects of colchicine and cytochalasin B on hypertonicity-induced changes in toad urinary bladder.

Coincident with an increase in the water permeability of toad urinary bladder induced by serosal hypertonicity, a transformation of the ridge-like surface structures of the granular cells into individual microvillous structures occurs. This study was initiated to establish whether the transformation is mediated by the cytoskeletal network and, thus, can be prevented by disruption of microtubule-microfilament function with colchicine or cytochalasin B (CB). Scanning electron microscopy revealed the characteristic branching ridges on granular cells of control bladder incubated with colchicine or CB. In contrast, transformation of ridges to discrete microvilli was observed in experimental bladders exposed to serosal hypertonicity alone or in combination with either colchicine or CB. These results suggest that the mechanism underlying hypertonicity-induced surface changes which are associated with increased water permeability does not involve either microtubules or microfilaments.

Animals↗
PubMed1982

The effects of cytochalasin B and colchicine on the morphogenesis of mitochondria in Drosophila hydei during meiosis and early spermiogenesis. An in vitro study.

Morphogenesis of mitochondria in male germ cells in cultivated cytocysts begins in early prophase I at which time mitochondria thicken and become ordered along the spindle apparatus during meiosis. At the end of the second meiotic division they aggregate to form the Nebenkern. In the presence of colchicine or cytochalasin B mitochondria are able to begin differentiation, although the correct course of meiosis is not guaranteed. In medium supplemented with colchicine they undergo normal thickening but do not aggregate, in a pattern known from untreated cultures. This may indicate that microtubules are involved in the aggregation process of mitochondria as colchicine is known to inhibit microtubule formation. Moreover, in cell cultures treated with cytochalasin B mitochondrial aggregation does occur; it is concluded that microfilaments, which are sensitive to cytochalasin B, do not play a detectable role in the aggregation of mitochondria.

Animals↗
PubMed1976

Colchicine effects on neurosecretory neurons and other hypothalamic and hypophysial cells, with special reference to changes in the cytoplasmic membranes.

The morphological effects of colchicine on the entire neurosecretory (NS) tract and on various hypothalamic nuclei have been studied. The perturbations in axonal flow, indicated by the accumulation of NS material, coincide with fragmentation of the cytoplasmic membranes, i.e. the Golgi apparatus and the endoplasmic reticulum, whereas the neurotubules remain relatively well preserved. Autophagic destruction of NS material is observed along the entire length of the NS fibres. The rapid and systematic changes in the axoplasmic reticulum, known to store calcium, lead us to envisage a role for this system-similar to that of the sarcoplasmic reticulum-in controlling the transport of NS vesicles. The junctional zone between the stalk and the neural lobe seems to play a particular role in the transport of NS material to the posthypophysial terminals of the NS axons. Colchicine provokes an increase in dense-cored vesicles in most of the neurons of the other hypothalamic nuclei studied: arcuate, suprachiasmatic, periventricular and ventromedial. Membranous alterations are also observed in these sites. Colchicine administered to animals which were hypothyroid, castrated or adrenalectomized, reveals stimulated neurons, identified by their excessive content of dense-cored vesicles. These neurons display no specific localization, for they occur in all hypothalamic nuclei, irrespective of the stimulation. The frequency of stimulation of neurons of the periventricular nucleus is striking.

Animals↗
PubMed1981

3H-fucose incorporation into bone following exposure to parathyroid hormone, dibutyryl cyclic-AMP and colchicine.

Radioautographic and scintillation counting procedures were used to examine the effect of parathyroid hormone (PTH), dibutyryl cyclic-AMP (DB-cAMP), and colchicine on the incorporation of 3H-fucose into macromolecular material in organ cultures of bone. Radioautography demonstrated 3H-fucose incorporation into bone cells, with the heaviest uptake occurring in osteoclasts. A minimal incorporation occurred in pre-osteoblasts and osteoblasts of the osteogenic periosteum, and in fibroblasts of the fibrous periosteum. PTH appeared to produce a heavier label in association with osteoclasts while decreasing the limited labeling associated with cells of the osteogenic and fibrous periosteum. DB-cAMP and colchicine both markedly reduced the labeling associated with osteoclasts, while the minimal labeling of other bone cells remained. By contrast, scintillation counting results indicated that PTH had little or no effect on 3H-fucose incorporation, while DB-cAMP and colchicine considerably reduced the amount of labeled macromolecular material. The incorporation of 3H-fucose into glycoproteins and the role of glycoproteins are discussed.

Animals↗
PubMed1987

Reduced excitatory effect of kainic acid on rat CA3 hippocampal pyramidal neurons following destruction of the mossy projection with colchicine.

Rats were injected unilaterally with colchicine in the dentate gyrus of the dorsal hippocampus. Two weeks later, under urethane anesthesia, extracellular recordings were obtained on both sides from pyramidal neurons of the CA1 and of the CA3 regions of the dorsal hippocampus. Microiontophoresis was used to assess the responsiveness of these neurons to kainate, glutamate and ibotenate. The colchicine injection produced a nearly complete destruction of the granule cells of the ipsilateral dentate gyrus and of their mossy fiber projections to CA3 without apparently affecting other hippocampal neurons. On the lesioned side, the potency of kainate in activating CA3 pyramidal neurons was reduced by 94% compared to the same neurons on the intact side. However, the excitatory effect of glutamate was unchanged and that of ibotenate only slightly reduced. Kainate was 80 times more potent in activating CA3 than CA1 pyramidal neurons on the intact side, whereas this ratio had dropped to 2.6 on the lesioned side. The selective decrease of the effectiveness of kainate in activating CA3 pyramidal neurons following the colchicine lesion suggests that this amino acid, but not glutamate and ibotenate, produces most of its excitatory effect in the intact CA3 region by releasing (an) excitatory neurotransmitter(s) from mossy fibers terminals, the nature of which remains to be identified.

Animals↗
PubMed1981

The effect of colchicine on the intracellular transport of 3H-fucose-labelled glycoproteins in the absorptive cells of cultured human small-intestinal tissue. An autoradiographical and biochemical study.

The effect of colchicine on the intracellular transport of 3H-fucose-labelled glycoproteins in the absorptive cells of cultured biopsy specimens of the human intestine was investigated by light- and electron-microscopical autoradiography and by biochemical methods. The results showed a decrease in the radioactivity of the cell coat on the microvilli and an increase in the Golgi apparatus and in the apical vesicles and tubules. This divergence is attributed to a colchicine-induced impairment of the normal transport of cell-coat glycoproteins from the Golgi apparatus, via the apical vesicles and tubules, to the apex of the cell. The radioactivity of the lysosome-like bodies in the absorptive cells cultured with colchicine also increased. This finding supports a crinophagic function of these organelles in the degradation of excess cell-coat material.

Biological Transport↗
PubMed1990

Effect of colchicine on lysosomal structures in maturation-ameloblasts of the rat incisor.

The lysosomal systems in maturation-ameloblasts affected by colchicine were examined using trimetaphosphatase cytochemistry. Demineralized segments of rat incisor were incubated for trimetaphosphatase. At all time intervals, lysosomal structures exhibited reduced enzyme reactivity and were clustered in the Golgi region of the cell. Both ruffle-ended and smooth-ended ameloblasts maintained essentially normal morphology up to 4 h after colchicine injection, except for some migration of organelles. After 8 h, the ruffled border was markedly modified and the associated dense granular material was no longer present. Changes in the lysosomal system and ruffled border indicate interference by colchicine with a putative resorptive function of the maturation-ameloblasts.

Acid Anhydride Hydrolases↗
PubMed1994

Epidermolysis bullosa acquisita--successful treatment with colchicine.

The treatment of epidermolysis bullosa acquisita (EBA) is difficult and often disappointing. We report on the successful treatment of two EBA patients with colchicine. The drug was administered orally at an initial dose of 2 mg/day. After 2 weeks of therapy a dramatic improvement was observed. Most of the cutaneous and buccal mucosal lesions had healed and both of the patients were able to go about their normal daily activities. In the first patient the disease was refractory to dapsone alone or combined with steroids. In the second patient no other treatment was tried. After 6 months a maintenance dose of 1 mg/day colchicine was given. The disease had remained stable in both patients at the time of writing for more than 8 months. No side effects were observed. We suggest that colchicine may be a helpful and safe drug for patients with EBA.

Administration, Oral↗
PubMed1982

Lack of correlation between trace metal staining and trace metal content of the rat hippocampus following colchicine microinjection.

Following the intrahippocampal injection of colchicine, the trace metal staining with Timm's method is shown to change in the hippocampus. The histochemical examinations were supplemented with atomic absorption spectrophotometric measurement of the trace metals (Zn, Fe, Cu). It was found that intrahippocampal colchicine treatment induces the temporary disappearance of the trace metal staining of the pyramidal cells of the regio superior, while there is a considerable reduction in the staining in the granular cells of the area dentata and in their mossy fibre terminals. Simultaneously, in contrast with the histochemical results, quantitative studies on the trace metal levels showed that colchicine does not lead to evacuation of the trace metals from the hippocampal formation. The combined atomic absorption and trace metal staining investigations prove that there is no correlation between the trace metal staining and the quantitative amounts of the trace metals.

Animals↗
PubMed1983

Colchicine-light effects on growth and mitotic behaviour in germinating lettuce achenes.

Root and shoot growth were severely suppressed in colchicine-pretreated lettuce achenes germinated in the dark and under illumination of 150 lux. Abnormal nuclear morphology rather than normal-appearing restitution nuclei was evident in these drug-pretreated achenes, there being no evidence of normal mitotic behaviour or cytokinetic activity in the root and shoot tissues examined. Root extension and lateral root meristem differentiation were evident in colchicine-pretreated achenes germinated under an illumination of 3000 lux, normal-appearing anaphase figures and cytokinetic activity being evident in both the primary root apices and lateral root meristems. Thus, the growth and mitotic behaviour of germinating colchicine-pretreated lettuce achenes were observed to be influenced significantly by the environmental light intensity in which germination occurred.

Cell Division↗
PubMed1990

Effects of colchicine on central and peripheral nerve terminals of the locust Schistocerca gregaria.

The treatment of locusts (Schistocerca gregaria) with colchicine leads to various changes in the ultrastructure of both central and peripheral nerve terminals. These changes include a marked reduction in synaptic vesicle density, which is further enhanced following stimulation. There are also increased numbers of coated pits and membraneous cisternae together with enlarged terminal areas and disruption of mitochondrial ultrastructure. The capacity of isolated central nerve terminals (synaptosomes) to take up the radiolabelled transmitter precursor [3H]-choline is enhanced following in vivo treatment of locusts with colchicine, whilst in vitro treatment leads to a reduction in choline uptake. The results are discussed with regard to the postulated effects of colchicine on axoplasmic transport.

Animals↗
PubMed1982

Gastrointestinal effects of long-term colchicine therapy in patients with recurrent polyserositis (familial mediterranean fever).

Twelve patients with recurrent polyserositis (RP, familial Mediterranean fever) on colchicine prophylaxis (1.0-2.0 mg daily) for three years or more were evaluated for the presence of gastrointestinal effects possibly attributable to the drug. Two patients had bulky stools, two others had transient diarrhea, and one had heartburn. Serum vitamin B12, calcium, and carotene levels were normal in all cases, and D-xylose absorption was normal in 11 of the 12. Three patients had mild steatorrhea (7.5, 7.9, and 9.9 g daily). Jejunal biopsies from these and a fourth patient with bulky stools but normal fecal fat excretion showed no abnormal histological changes. However, (Na + K)-ATPase activity was significantly decreased in all four cases. Colchicine had to be discontinued in only one of the 12 cases. It is concluded that mild steatorrhea and enzyme inhibition may occur in patients on long-term colchicine prophylaxis and that careful periodic observations for this and other adverse effects is imperative in such patients.

Adolescent↗
PubMed1978

Colchicine inhibition of ADH effect on frog skin permeability.

ADH and AMPc enhance both thiourea unidirectional fluxes in frog skin. This effect is completely abolished by colchicine pretreatment. The ADH increase of thiourea discharge with or without colchicine led us to suppose that colchicine does not directly affect ADH action on outer membrane permeability, but exerts its effects on a site which is limiting for the ADH action on transepithelial permeability.

Animals↗