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Biomedical subjects

M Mian

Publications and source records attributed to M Mian.

At least 73 records · Page 4Linked to original sources

Effects of diacerein on the quantity and phagocytic activity of thioglycollate-elicited mouse peritoneal macrophages.

Diacerein (DAR: 1,8-diacetoxy-9,10-dioxo-dihydroanthracene-3-carboxylic acid) is an anthraquinone drug which displays anti-inflammatory effects in experimental animals and antirheumatic activity in humans. The drug was administered for orally for four consecutive days to mice injected intraperitoneally with thioglycollate. The following dose levels of DAR were used: 2.5, 5 and 10 mg/kg/day. At the end of the experimental period the macrophage content of peritoneal exudate was dose-dependent and significantly lower in DAR-treated mice compared with animals that were given saline orally. The macrophages isolated from the peritoneal exudate of mice that received DAR displayed a dose-dependent reduced phagocytosis. The effects of DAR were found to be similar to those of indometacin and dexamethasone, which were used as reference drugs. The ability of DAR to interfere with macrophage functioning may contribute to its overall therapeutic activity.

Animals↗

Rhein reduces proteoglycan loss during the autolytic breakdown of cultured cartilage.

Rhein (R: 1,8-dihydroxy-3-carboxyanthraquinone) is the active metabolite of the drug diacerhein (DAR), an anthraquinone molecule which has recently been proposed for the long-term treatment of osteoarthrosis. In the present study we have examined the effects of rhein, as compared to indomethacin or hydrocortisone, on an in-vitro model of cartilage degradation, represented by the autolytic breakdown of the articular cartilage excised from rabbit knee and cultured for seven days. During this period there is a spontaneous loss of proteoglycans. At the end of the period we measured the amount of proteoglycans which remained bound to the cartilage. The samples treated with R revealed dose-dependent modifications in the amounts of cartilage-bound proteoglycans, with a 40% increase as compared with non-treated samples at the dose of 7 x 10(-5) M. We conclude that R shows a protective effect on the articular cartilage, and that at least a part of the beneficial effect that DAR has shown in the course of clinical trials in osteoarthrosis may be due to direct effects of its active metabolite (R) on cartilaginous tissue.

Animals↗

Serum interleukin-2 receptor levels measured by enzyme immunoassay in heart and kidney transplanted patients.

IL-2R serum concentrations were assayed by a sandwich enzyme immunoassay method in order to ascertain if the measurement of the soluble form of IL-2R can be considered a useful marker of allograft rejection in heart and kidney transplanted patients. Serum IL-2R levels increased significantly compared to pre-operated values (1129 +/- 215 U/ml vs. 592 +/- 209 U/ml, p less than 0.01) in six heart-transplanted patients during acute rejection crises documented by clinical findings and endomyocardial biopsy, and returned to baseline levels after successful treatment (544 +/- 395 U/ml vs. 1129 +/- 215 U/ml, p less than 0.01). Moreover, we observed that severe bacterial (n = 5) or viral (n = 2) infections were also accompanied by a significant increase of IL-2R serum levels in heart-transplanted patients (1076 +/- 263 U/ml vs. 486 +/- 146 U/ml, p less than 0.01 in bacterial, and 1290 +/- 368 U/ml vs. 370 +/- 85 U/ml in viral infections). In the six patients with renal transplant, the mean pre-operative IL-2R level was also elevated (1507 +/- 203 U/ml). A 1.5-4 fold increase of IL-2R levels has been observed at the beginning of both acute rejection and clinically evident infection. Our data show that the serum concentration of IL-2R is increased in heart and kidney transplanted patients during allograft rejection crisis. However, the information gained with this assay must be cautiously interpreted because an increase of IL-2R concentrations can also indicate bacterial or viral infections.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PAF-induced histamine release in the isolated perfused rat kidney.

The platelet-activating factor (PAF) has been shown to stimulate the release of prostaglandins, leukotrienes and 5HT from a number of cell types. In this work we studied the effects of bolus injections of PAF on the isolated perfused rat kidney. Results showed histological damage at the proximal-tubule level and a significant histamine release.

Animals↗

The protective action of a water poor in calcium on the liver and digestive apparatus of guinea-pigs chronically treated with 9-alpha-fluoro-16-beta-methylprednisolone.

An evaluation was made of the possibility of exerting a protective action by administering natural water with a very low saline content, equal to 22 mg/l (oligomineral water), during the course of prolonged treatment with 9-alpha-fluoro-16-beta-methylprednisolone. The study was carried out using guinea-pigs (66 animals in all, of both sexes, clinically healthy, and of standard weight), which were divided into four groups which received, respectively: 9-alpha-fluoro-16-beta-methylprednisolone and aqua fontis, 9-alpha-fluoro-16-beta-methylprednisolone and oligomineral water, aqua fontis by itself, and oligomineral water by itself. Examinations carried out after thirty-four days of experimentation showed that the histomorphological damage to the liver and the digestive apparatus caused by the cortisonic therapy appeared to be considerably reduced and possibly eliminated when this therapy was combined with adequate administration of oligomineral water, such as the one considered in the present experiment.

Animals↗

The protective action of a water poor in calcium on the kidney of guinea-pigs treated with 9-alpha-fluoro-16-beta-methylprednisolone.

A series of experiments was conducted on guinea-pigs treated with 9-alpha-fluoro-16-beta-methylprednisolone in order to evaluate the histomorphological damage to the renal parenchyma. Animals that were subjected at the same time to hydropinic therapy based on a mineral water with a very low saline content (oligomineral waters) exhibited far less damage than the control group which received aqua fontis.

Animals↗

The use of waters with a low saline content (oligomineral waters) in the feeding of babies.

The problem of the dilution of foodstuffs for early infancy is discussed, with particular reference to artificial milks. The authors briefly consider the influence of calcium salts in the course of curdling, both for milks enriched with such salts and in diluted milks, as well as the importance of a correct well-dosed saline content in the diet for the early stages of infancy. They then control experimentally, using scalar dilutions (1:100; 1:1000; 1:5000) of pepsin at a known titre, the coagulation of commercial powdered milk and of fresh cow's milk, diluted with various types of mineral waters (chlorinated-sodic oligomineral water; bicarbonate-calcic oligomineral water; bicarbonate-alkaline-terrous mineral water).

Animals↗

Adriamycin, aclacinomycin and thepirubicin intracardiac distribution examined by fluorescence microscopy.

Male Wistar rats received adriamycin, aclacinomycin or thepirubicin at a dose of 4 mg/kg b.w. by slow infusion. Cardiac tissue sections were examined by fluorescence microscopy to evaluate the distribution of the three anthracyclines. The nuclei regularly exhibited a stronger coloring with respect to the cytoplasm for all three drugs. Adriamycin cytoplasm fluoresced intensely, unlike aclacinomycin and thepirubicin. Our results indicate a lower uptake of these last two molecules into cardiac tissue, thus suggesting a different pharmacokinetic profile which might account for their lower cardiotoxicity.

Aclarubicin↗

Skin penetration of CoQ10 in the rat.

Skin penetration of coenzyme Q10 (CoQ10) was investigated after topical treatment in the rat. The drug was suspended in olive oil and administered at two different concentrations. Coenzyme levels were found to be directly related to the concentrations employed and the contact time. CoQ10 topical treatment might therefore be proposed as a good pharmacological tool in dermatology and cosmetology.

Absorption↗

Plasma and tissue concentrations of coenzyme Q10 in the rat after its oral administration.

Coenzyme Q10 (CoQ10) kinetics was investigated in rat tissues after oral treatment. CoQ10 passes quickly from plasma into the tissue examined, reaching levels higher than physiological ones; the liver shows the maximal CoQ10 concentrations. Our results indicate that oral treatment makes it possible to obtain good tissue levels of CoQ10 that might be of clinical value against endogenous CoQ10 insufficiencies due either to pathological alterations and/or to drug administration.

Administration, Oral↗

Plasma and tissue concentrations of coenzyme Q10 in the rat after intravenous administration by a microsphere delivery system or in a new type of solution.

Coenzyme Q10 (CoQ10) distribution into rat liver, heart, kidney, and plasma was investigated after intravenous administration in microsphere delivery system and in solution. The liver represented the target organ for this compound in both cases. Higher plasma levels of CoQ10 were achieved after solution treatment. No significant differences were detected in the other tissues examined.

Animals↗

N-acetyl-beta-glucosaminidase (NAG) and alpha-glycosidase released by PAF in isolated perfused rat kidney.

The action of PAF is involved in various biological activities, including alterations at the renal level. Previous experiments of ours have shown that PAF is capable of inducing histamine release at this level, and causing histological damage in the isolated perfused rat kidney. On the basis of these observations, the same experimental model was used to evaluate the release of enzymes such as NAG and alpha-glycosidase, which are precocious markers of renal damage. Results show that both NAG and alpha-glycosidase increase after PAF administration.

Acetylglucosaminidase↗

Aclacinomycin tissue distribution in the rat.

This study was undertaken to investigate aclacinomycin distribution in the rat, using a method based on the histofluorescence of tissues treated in vivo with anthracyclines. The target organs were the kidney, lung and pancreas; a fainter fluorescence was also detected in the heart compared with adriamycin due to a quantitatively different fixing of the two anthracyclines. Our findings revealed a preferential uptake into the cell nucleus in all tissues examined except the adrenal gland medulla where a slight fluorescence appeared only in the cytoplasm.

Aclarubicin↗

Rhein: an anthraquinone that modulates superoxide anion production from human neutrophils.

Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid), the active metabolite of diacetylrhein, which has been reported as an effective antirheumatic drug in man, inhibited superoxide anion production from human neutrophils challenged with N-formylmethionyl-leucyl-phenylalanine (FMLP: IC50, 2 x 10(-5) M) and A23186 (IC50, 10(-5) M), but not with phorbol myristate acetate. In the same concentration range (10(-6)-10(-3) M), the drug did not affect oxy-radical production by a cell-free hypoxanthine-xanthine oxidase system and exerted weak inhibitory effects on FMLP-evoked lysosomal enzyme release. Rhein inhibitory effects on neutrophil functioning may contribute to the overall therapeutic activity of the parent drug, diacetylrhein.

Adult↗

Histological changes and histamine release induced by dactimicin in isolated perfused rat kidney.

The nephrotoxicity of aminoglycosides has been the object of numerous works of research showing that different molecules belonging to the same family of antibiotics can exert their toxic action in different ways. The aim of the present research was to evaluate the nephrotoxicity of dactimicin (DTC), a recently synthesized aminoglycoside antibiotic, as compared to gentamicin (GTM), amikacin (AMK) and fortimicin (FTM). The experimental model used was the isolated perfused rat kidney, and the parameters evaluated were histamine release and histological findings. The results showed that GTM was able to induce a significantly higher release of histamine than AMK, FTM, or DTC. AMK provoked a higher level of histamine release than FTM or DTC, although the differences between the three were not significant. Histological preparations obtained with GTM revealed large-scale lesions, which however were less detectable with AMK, and much less with DTC.

Aminoglycosides↗

Experimental studies on diacerhein: effects on the phagocytosis of neutrophil cells from subcutaneous carrageenan-induced exudate.

Diacerhein (DAR), a new drug which is particularly suitable for the treatment of osteoarthritis, was studied for its interference with the phagocytic capacity of cells coming from exudates of subcutaneous carrageenan oedema and from the peripheral blood of Sprague-Dawley rats. DAR was found to inhibit phagocytosis in both types of cells examined. This finding indicates that DAR may exert its action by means of a direct effect on the cells involved in the inflammatory process.

Animals↗

Studies in vitro on the effects of rhein on the chemotaxis of human leukocytes.

Rhein (R: 1,8-dihydroxy-3-carboxyanthraquinone) is the active metabolite of the drug diacetylrhein (DAR), an anthraquinone molecule which has recently been proposed for the long-term treatment of osteoarthrosis. Its action mechanism in rheumatic pathology has not been fully explained. It is known that DAR, while not inhibiting the formation of prostaglandins, inhibits certain proteolytic enzymes, and acts on phlogistic cells by lysosomal enzymic and superoxide-anion modifications. Moreover DAR modifies phagocytic functions and the motility of cells. This paper is a contribution to the clarification of the last point, namely the effect of rhein on cell motility. It reports that in vitro no effect of R on random migration was found, but instead a double inhibiting effect on chemotaxis (i.e. a low-dosage and a high-dosage effect). Furthermore, R did not modify the inhibition or induce modification of chemotaxis by vinblastine. Finally R cancelled the stimulating effect of ionic potassium. The results thus indicate that R acts on the chemotaxis of the leukocytes with a complex action at different doses. The action mechanism is probably due to a membrane effect, since rhein (R) did not modify the chemotaxis-inhibiting activity of vinblastine but did interfere with the stimulating effect of K+.

Anthraquinones↗