potassium-permanganate and Calcinosis

Calcinosis cutis is a disorder caused by abnormal deposits of calcium phosphate in the skin and is observed in diverse disorders. Myo-inositol hexaphosphate (InsP(6)) is a diet-dependent molecule found in all mammalian fluids and tissues, which exhibits an extraordinary capacity as a crystallization inhibitor of calcium salts.. To establish the effects of topically administered InsP(6) cream on artificially provoked dystrophic calcifications in soft tissues.. Fourteen male Wistar rats were randomly assigned into two groups: control and treated groups. Rats were fed with an InsP(6)-free or phytate diet. Plaque formation was induced by subcutaneous injection of 0.1% KMnO(4) solution. From 4 days before plaque induction to the end of the experiment, control rats were treated topically with a standard cream, whereas treated rats were treated with the same cream with 2% InsP(6) or phytate (as sodium salt). Calcification of plaques was allowed to proceed for 10 days. InsP(6) in urine was determined. The plaques were excised and weighed.. It was found that when InsP(6) was administered topically through a moisturizing cream (2% InsP(6)-rich), the plaque size and weight were notably and significantly reduced compared with the control group (1.6 +/- 1.1 mg InsP(6)-treated, 26.7 +/- 3.0 mg control). The InsP(6) urinary levels for animals treated with the InsP(6)-enriched cream were considerably and significantly higher than those found in animals treated topically with the cream without InsP(6) (16.96 +/- 4.32 mg L(-1) InsP(6)-treated, 0.06 +/- 0.03 mg L(-1) control).. This demonstrates the important capacity of InsP(6) as a crystallization inhibitor and also demonstrates that it is possible to propose topical use as a new InsP(6) administration route.

Topics: Administration, Cutaneous; Animals; Calcinosis; Male; Ointments; Phytic Acid; Potassium Permanganate; Rats; Rats, Wistar; Skin Diseases

Myo-inositol hexaphosphate (InsP6) is an abundant component of plant seeds. It is also found in significant levels in blood and mammalian tissues, but they are totally dependent on their dietary intake. In the present paper, we describe studies on the effect of InsP6 on a model of dystrophic calcification, which was chemically induced by subcutaneous injection of a 0.1% KMnO4 solution. Male Wistar rats were randomly divided into four groups for treatment over 31 days. A: animals consuming a purified diet in which InsP6 was absent but to which 1% of InsP6 (as sodium salt) was added. In this group, the InsP6 plasma levels (0.393 +/- 0.013 microM) were similar to those observed in rats consuming a standard diet. B: animals consuming only the purified diet in which InsP6 was absent. In this case the InsP6 plasma levels decreased (0.026 +/- 0.006 microM); C: animals consuming the same purified diet as group B but received daily subcutaneous injections of 50 microg kg(-1) etidronate during the last 14 days. In this case the InsP6 plasma levels were also very low (0.025 +/- 0.007 microM); D: animals consuming the same diet as group B but a 6% of carob germ (InsP6 rich product) was added. The InsP6 plasma levels (0.363 +/- 0.035 microM) were also similar to those observed in rats consuming a standard diet. After 21 days plaque formation was induced. Calcification plaques were allowed to proceed for 10 days, after which the plaque material present was excised, dried and weighed. It was found that the presence of myo-inositol hexaphosphate (phytate) in plasma at normal concentrations (0.3-0.4 microM) clearly inhibited the development of dystrophic calcifications in soft tissues. These results demonstrates that myo-inositol hexaphosphate acts as an inhibitor of calcium salt crystallization.

Topics: Administration, Oral; Animals; Calcinosis; Diet; Disease Models, Animal; Etidronic Acid; Injections, Subcutaneous; Male; Phytic Acid; Pilot Projects; Potassium Permanganate; Rats; Rats, Wistar

Monocyte chemotactic protein-1 (MCP-1) and related molecules constitute the C-C class of the beta chemokine supergene family with inflammatory properties. However, the exact role, function, and implication in inflammatory diseases remain to be determined. Here we report that subcutaneous injections (0.2 ml) of a saturated water solution (1:40) of potassium permanganate crystals induces the generation of granuloma tissue at the site of injection in the rat, and reaches its peak of formation after 1 week. The size and weight of the granulomas were increased by i.p. lipopolysaccharide (LPS) (6 microgram/200 microliter) and inhibited by intraperitoneal (i.p.) dexamethasone (Dxs) 300 microgram/200 microliter) treatments in rats, injected 18 hours before sacrifice. Moreover, steady-state levels of MCP-1 mRNA in the granuloma tissue (control), were strongly generated. Rats treated i.p. with LPS produced an increase of MCP-1 mRNA in the granuloma tissue compared with controls (i.p. PBS-treated) whereas in animals treated with Dxs, there was a decrease in (P < 0.05) in formation of mRNA protein. When the granuloma tissues were homogenized the generation of MCP-1 was found in the supernatants. The level of MCP-1 was higher (P < 0.05) in the LPS-treated animals and lower (P < 0.05) in the Dxs group compared with the controls (treated with PBS). Similar results were obtained in the serum and in minced granuloma tissue where samples were further incubated in vitro with LPS (100 ng/ml) overnight. A Strong increase (P < 0.01) in MCP-1 in all samples was detected, but not in the minced granuloma tissue from Dxs-treated animals. Our data demonstrate that calcified tissue from chronic inflammation induced by KMnO4 generates MCP-1 gene expression and translation, an effect increased by LPS and decreased by Dxs.

Topics: Animals; Calcinosis; Chemokine CCL2; Gene Expression Regulation; Granuloma; Lipopolysaccharides; Male; Potassium Permanganate; Protein Biosynthesis; Rats; Rats, Wistar; RNA, Messenger

The subcutaneous injection of mast cell degranulators in the mouse is followed by calcification of fibres of the Panniculus Carnosus muscle. This reaction is seen in damaged fibres adjacent to a central zone of complete necrosis. Calcification of muscle fibres is also seen after the injection of KMnO4 but this uniformly affects the fibres at the site of reaction. Quantitative studies of the latter model and qualitative studies of the former show that treatments with the diphosphonates EHDP and Cl2MDP do not influence the calcific responses. It is suggested that the inducing chemicals interact with the muscle fibre membrane causing membrane dysfunction and a resultant influx of calcium ions. It has been proposed that this is a pathogenetic mechanism in various myopathies and that prevention of net calcium ion influx might form a basis for treatment. In this context, the results of the present experiments suggest that the diphosphonates would be unlikely to efficacious in this regard.

Topics: Animals; Calcinosis; Clodronic Acid; Etidronic Acid; Hexadimethrine Bromide; Male; Mice; Muscles; Muscular Diseases; p-Methoxy-N-methylphenethylamine; Polymyxin B; Potassium Permanganate

The subcutaneous injection of small quantities of LaCl3 and CeCl3 was followed by calcification of the dorsal fascia in mice. The calcification reaction was shown by separate positive histochemical tests for calcium ions (the chloranilic acid reaction) and phosphate (the von Kossa reaction). The injection of cadmium chloride and stannous salts caused damage to and a positive von Kossa reaction in the fibres of the panniculus carnosus muscle. The significance and specificity of the histochemical tests was determined by X-ray microprobe analysis of tissues injected with the above salts and other salts known to cause either combined chloranilic acid and von Kossa positive reactions or isolated von Kossa positive reactions in mouse skin. The pathogenesis of the reactions produced by LaCl3, CeCl3 and KMnO4 was studied by applying histochemical tests to tissues recovered at timed intervals after injection. The reactions produced by LaCl3 and CeCl3 were similar and occurred in the dorsal fascia with positive VK reactions occurring first after 18 followed by positive CA reactions after 24 hr. The distribution of these reactions suggested a haematogenous origin for the constituent ions. The injection of KMnO4 in a much higher dose caused damage to the skin and particularly the fibres of the panniculus carnosus muscle. In contrast to the other salts, the calcific reaction occurred in association with these fibres, showing equally positive von Kossa and chloranilic acid reactions from the early stages.

Topics: Animals; Calcinosis; Chlorides; Fascia; Male; Mice; Potassium Permanganate; Salts; Skin; Skin Diseases

Hydroxyapatite crystal deposition is thought to play a role in the inflammatory episodes of osteoarthritis. A plaque of hydroxyapatite crystals was produced by local subcutaneous injection of a potassium permanganate solution. Transmission electron microscopy with X-ray energy spectroscopy was used to identify the crystal deposits as hydroxyapatite. The effects of dexamethasone, indomethacin, ethane 1-hydroxy-1, 1-diphosphonate (EHDP) and dichloromethylene diposphonate (Cl2MDP) on the development of the apatite plaque was studied. EHDP strongly inhibited the apatite deposition. Cl2MDP slowed the natural resorption of the apatite plaque. Dexamethasone and indomethacin failed to affect the crystal deposition process. The results suggest that EHDP could inhibit crystal deposition in the osteoarthritic joint and that Cl2MDP might have a role in slowing apatite crystal shedding from osteoarthritic cartilage and so reduce the synovitis seen in Osteoarthritis.

Topics: Animals; Calcinosis; Clodronic Acid; Dexamethasone; Disease Models, Animal; Etidronic Acid; Hydroxyapatites; Indomethacin; Male; Osteoarthritis; Potassium Permanganate; Rats; Spectrophotometry, Infrared; Time Factors

The subcutaneous injection into mice of small quantities of lead salts resulted in calcification of the dorsal fascia. Other reputed calcergens failed to produce a similar reaction. However, the injection of Zn Cl2 and KMn O4 in high doses caused damage to, and subsequent calcification of the panniculus carnosus muscle.

Topics: Animals; Calcinosis; Fascia; Lead; Male; Mice; Muscles; Potassium Permanganate; Salts; Zinc

Mineralized plaques, which develop at the site of repeated subcutaneous injections of 100 mug KMnO4/0.2 H2O in rats, were investigated by electron microscopy. The newly formed, delineated, white plaque tissue at the injection site consisted of numerous, mostly unaltered fibroblasts and collagen fibers, without participation of inflammatory cells. Some signs of cell injury were found in the center of the lesions. Numerous, irregularly distributed, small, mineralized foci were seen near the fibroblasts. These were formed by aggregation of small needle-like units (50 A in diameter and 0.05-2.0 mum long). These needle-shaped units were found either in vesicular, cell derived structures, considered to be shed cell fragments, or on collagen fibers. Intramitochondrial deposits of such needle like units were seen frequently. Fusion of smaller mineralized foci to larger plaques occured and then needle-shaped units were seen at the periphery of the electron-dense lesions. Hypotheses concerning the mechanism of experimental cutaneous calcinosis (soft tissue mineralization) are discussed and related to the findings of this study. Probable intracellular crystal deposition and mineralization in cell-derived structures were shown for the first time in topical cutaneous calcinosis.

Topics: Animals; Calcinosis; Cell Membrane; Collagen; Connective Tissue; Fibroblasts; Inclusion Bodies; Mitochondria; Potassium Permanganate; Rats; Skin; Skin Diseases

Topics: Anaphylaxis; Animals; Calcinosis; Calciphylaxis; Calcium; Calcium Chloride; Cerium; Connective Tissue; Dextrans; Dihydrotachysterol; Edema; Egg White; Female; Iron-Dextran Complex; Lead; Mast Cells; Polymyxins; Potassium Permanganate; Rats; Triamcinolone

Topics: Animals; Autoradiography; Calcinosis; Calcium; Cornea; Corneal Injuries; Dihydrotachysterol; Epithelium; Eye Diseases; Fibroblasts; Freezing; Guinea Pigs; Histocytochemistry; Injections; Potassium Permanganate; Rabbits; Radiography; Radioisotopes; Rats; Time Factors

Topics: Animals; Calcinosis; Calciphylaxis; Connective Tissue; Edema; Female; Mast Cells; Potassium Permanganate; Purpura; Rats; Salicylates; Skin Diseases

Topics: Anaphylaxis; Animals; Calcinosis; Calciphylaxis; Connective Tissue; Dihydrotachysterol; Edema; Female; Foot Diseases; Formaldehyde; Hemorrhage; Inflammation; Ischemia; Lead; Necrosis; Pharmacology; Potassium Permanganate; Rats; Serotonin; Stress, Physiological; Thrombosis

Topics: Acetates; Animals; Calcinosis; Calciphylaxis; Calcium Chloride; Cerium; Chlorides; Female; Lead; Metals; Potassium Permanganate

Topics: Age Factors; Alkaline Phosphatase; Animals; Calcinosis; Female; Fibroblasts; Glycosaminoglycans; Histocytochemistry; Male; Microscopy, Electron; Potassium Permanganate; Rats; Skin Diseases

Topics: Alkaline Phosphatase; Animals; Calcinosis; Calciphylaxis; Diphosphates; Female; Male; Potassium Permanganate; Radiography; Rats; Skin Diseases

Topics: Calcinosis; Calciphylaxis; Dihydrotachysterol; Pharmacology; Potassium Permanganate; Rats; Research; Sclerosis; Trachea

Topics: Calcification, Physiologic; Calcinosis; Calcium, Dietary; Diet; Phosphates; Potassium Permanganate; Rats; Research