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[Intra-arterial infusion chemotherapy with side-hole catheter for primary and metastatic liver, bile duct, and pancreas cancers].

Dislodgement and obstruction of catheter inserted into the artery are great hazards for the hepatic artery infusion chemotherapy. To prevent dislodgement, a new Anthron-coated catheter with a side hole was applied for the treatment of 32 patients with primary and metastatic liver cancer, bile duct cancer and pancreas cancer. The tip of the catheter was advanced deep into the gastroduodenal artery, proper or right hepatic artery, or splenic artery. Anti-cancer drugs were administered through the proximal side hole for targeting cancer. If necessary, the gastroduodenal artery was occluded with a metal coil. No dislodgement or obstruction of the catheter was noticed in the 32 patients thus treated. The new Anthron-coated catheter with a side hole proved to be useful for prevention of catheter dislodgement and accomplishment of long-term intra-arterial infusion chemotherapy.

Aged↗

[A study of complications of hepatic arterial infusion catheter].

We studied complications of the infusion catheter, which were implanted in the hepatic artery under laparotomy, and then connected with an implantable infuser port in patients with hepatocellular carcinoma (n = 32) and metastatic liver tumor (n = 11). Infuse-A-Port catheter was used for 31 cases (A group), and Anthron P-U catheter for 12 cases (B group). In B group, the cannulation method was changed; the catheter was placed in the hepatic artery via the gastroduodenal artery, which was ligated and cut to prevent kinks in the catheter. In the A group, 17 cases (54.8%) showed complications such as dislocation of the catheter tip (7 cases) including penetrating duodenal ulcer (2 cases), arterial occlusion (6 cases), injury of catheter (2 cases) and occlusion of the infuser port (2 cases). One case, however, having a fistula between the hepatic artery and the duodenum, died of sudden massive bleeding. In the B group, 3 cases (25.0%) showed complications such as dislocation of the catheter tip (1 case) and arterial occlusion (2 cases). The catheter in B group lasted longer than that in A group. Thus, our cannulation technique using Anthron P-U catheter may decrease the catheter complications.

Catheters, Indwelling↗

Dermal absorption and metabolism of the antipsoriatic drug dithranol triacetate.

Percutaneous absorption, excretion kinetics, and metabolism of dithranol triacetate (2) have been investigated in Wistar rats. By the use of two differently labelled molecules--3H in the anthracene nucleus and 14C in the acetoxy groups of 2, resp.--the fate of the different parts of the dithranol triacetate molecule could be followed. After injection, large amounts of 2 are cleaved under the influence of enzymes into acetate and dithranol. These deacetylated metabolites lose half their 3H label with formation of 3H2O. In urine, 1,8-diacetoxy-9-anthrone, 1-acetoxy-8-hydroxy-9-anthrone, 1,8-dihydroxy-9,10-anthraquinone and its diacetate were found as metabolites. After dermal application, unchanged 2 is practically not absorbed at all. Arylesterases which, according to in vitro studies, are present in or on the skin, hydrolyse dithranol triacetate to give free dithranol. Up to 33% of the latter are absorbed from under an occlusive dressing. Dithranol triacetate, therefore, shows pro-drug characteristics for the treatment of psoriasis.

Administration, Oral↗

Carbohydrate malabsorption is minimal in school-age cystic fibrosis children.

Fifteen school-age cystic fibrosis children, participating in a year-long nutritional management study, were hospitalized at six-month intervals for balance studies during which they continued "free-choice" diets and their usual enzyme supplementation. Stools were analyzed for fat and protein by conventional methods and for carbohydrate using a recently validated anthrone method. Despite persistent fat and protein malabsorption, less than 1% of ingested carbohydrate was lost intact in the stools. Comparison of baseline and placebo balance studies showed fecal excretion of carbohydrate to be independent of intake, in contrast to the fat and protein results. Using a thin-layer chromatography method capable of detecting microgram quantities of urinary organic acids, no short-chain fatty acids were detected in the stool. Further exploration of carbohydrate as a dietary energy source for this patient group with increased energy demands should be pursued.

Adolescent↗

A potentiometric method for the determination of the iodine-binding capacity of glycogen.

The experimental conditions in the potentiometric method for the determination of the iodine-binding capacity (Ib) of starch and amylose [R. L. Bates, D. French, and R. E. Rundle (1943) J. Amer. Chem. Soc. 65, 142-148] were not suitable for glycogen because of the much lower affinity for iodine of the latter. This difficulty was overcome by titration of small volume with both the iodine and glycogen at high concentration. Using the concentration cell circuit Pt electrode-blank-bridge-glycogen-Pt electrode, small increments of standard iodine solution were added to the blank solution and each was titrated to null by adding iodine to the glucogen solution [G. A. Gilbert and J. V. R. Marriott (1948) Trans. Faraday Soc. 44, 84-93]. Glycogen was determined by an anthrone-sulfuric acid method [F. W. Fales (1951) J. Biol. Chem. 193, 113-124]. Glycogens with Ib's ranging from 1.8 to 5.3% were observed.

Animals↗

A micromethod for the enzymatic estimation of the degree of glycogen ramification.

A comparison of methods for the evaluation of glycogen content in liver tissue of rats has been carried out by determining the recoveries in the differential ethanol precipitation of glycogen from alkaline tissue digests as well as the actual quantitative equivalence between glycogen content and actual glucose measured. Hydrolytic/enzymatic methods gave lower results than non-specific chemical methods such as anthrone. These lower values, combined with the losses in the purification process resulted in much lower glycogen estimations than the actual estimated tissue content. A method has been devised for the measurement of glycogen ramification in small liver tissue samples, using neutral periodate oxidation of the molecule, followed by determination of the formic acid evolved from the branch ends with formic acid dehydrogenase. The method gave results very similar to the classical methods in which the acid formed is measured titrimetrically. Rat liver tissue contained a mean 323 +/- 69 mmol of glucose equivalents of glycogen per gram of tissue; this glycogen had a mean chain length of 11.4 +/- 0.8 units.

Animals↗

Tyrosine kinase inhibitors, emodin and its derivative repress HER-2/neu-induced cellular transformation and metastasis-associated properties.

We have previously shown that emodin suppresses tyrosine kinase activity of HER-2/neu-encoded p185neu receptor tyrosine kinase. In this study, we examine the relationship between the chemical structure and the activity of emodin and nine derivatives, and identified that one methyl, one hydroxy, and one carbonyl functional groups are critical for the biological activities of emodin. We also found that one of the derivatives 10-(4-acetamidobenzylidene)-9-anthrone (DK-V-47) is more effective than emodin in repressing the tyrosine phosphorylation of p185neu and in inhibiting the proliferation and transformation of HER-2/neu-overexpressing human breast cancer cells. Using mutation-activated HER-2/neu transformed 3T3 cells, we also investigated whether emodin and DK-V-47 can inhibit malignant transformation induced solely by the HER-2/neu oncogene. We found that DK-V-47 is more potent than emodin in suppressing transformation phenotypes of activated HER-2/neu transformed 3T3 cells including anchorage-dependent and -independent growth, metastasis-associated properties. These results clearly indicate that the inhibition of p185neu tyrosine kinase by both emodin and DK-V-47 is capable of suppressing the HER-2/neu associated transformed phenotypes including the ability to induce metastatic potential. Our results also support the chemotherapeutic implications of the use of either emodin or DK-V-47 to target HER-2/neu-overexpressing cancer cells.

3T3 Cells↗

The combination between hemolysins and red cells or ghosts, as studied with a radioactive lysin and with new color reactions.

The quantity of a radioactive hemolysin, sodium dodecyl sulfonate-S(35), taken up by red cells from concentrations too small to produce hemolysis varies with the lysin concentration, and does so in a way which can be described by an adsorption isotherm. Attempts to use color reactions or surface tension measurements to determine the quantity of digitonin, saponin, and the bile salts taken up by red cells from hypolytic concentrations have failed, principally because chromogenic, and also surface-active, substances are liberated from the cells when the lysin is added. Color reactions with the anthrone reagent show that digitonin and saponin are both taken up by or fixed to red cell ghosts; the extent of the uptake, however, is uncertain, again because of the liberation of chromogenic substances. Comparison of the results of the various methods which measure the apparent amount of lysin fixed, or utilized in reactions between lysins and red cells or ghosts show discrepancies between results given by direct methods (measurement of radioactivity or of color) and indirect methods (addition of a second population after lysis of a first, and dependence of the position of the asymptote of the time-dilution curve on the number of red cells). The discrepancies are traceable to the inhibitory effects of substances liberated from the red cells or ghosts. The ease with which a lysin, once taken up by red cells, can be detached by diluting the system determines the extent to which the hemolytic reaction is "progressive," but has no observed connection with the quantity taken up in the first place. There is now ample evidence that lysis in systems containing simple hemolysins is a process involving two stages in time and two phases, and that it is usually complicated by reactions between the hemolysin and liberated inhibitory material.

Anthracenes↗

Effect of senna is not mediated by platelet-activating factor.

The effect of in vivo treatment with senna was examined on the ex vivo formation of platelet-activating factor (PAF) by small and large intestine of rat, mouse and guinea pig. A single or a prolonged oral administration of senna (60-240 mg/kg) to animals did not increase intestinal PAF content. Nor did senna increase the intraluminal release of acid phosphatase. A similar result was obtained in the colonic tissue of rat perfused in vitro with rhein (1-500 micrograms/ml) or rhein anthrone (1-500 micrograms/ml). In contrast, a single oral administration of phenolphthalein (20 mg/kg), bile salts (20 mg/kg) or magnesium sulfate (30 mg/kg) to rats increased intestinal PAF content. Magnesium sulfate also increased the intraluminal release of acid phosphatase. Colonic tissue of rats perfused in vitro with calcium ionophore A23187 (10 micrograms/ml) formed large amounts of PAF and acid phosphatase. PAF stimulates intestinal motility and secretion and mediates gut damage while acid phosphatase is a marker of cellular damage. Therefore, our data suggest that senna is well tolerated in animals and PAF does not mediate senna-induced laxation.

Acid Phosphatase↗

Acidogenic potential and total salivary carbohydrate content of expectorants following the consumption of some cereal-based foods and fruits.

The acidogenic potential of a group of popular cereal-based foods and fruits and total carbohydrate content of salivary expectorants following their consumption were assessed using an indwelling electrode with telemetry and the anthrone method. Paired t tests indicated that sorbitol did not cause the plaque pH to fall as low as any of the test foods (p <0.05) but there was no significant difference between sucrose and the test foods. Only the fruits produced less acid than sucrose. The breakfast cereals tended to yield the highest levels of total carbohydrate in the salivary expectorants although a greater percentage of original carbohydrate was retained after rice and bread. These results suggest the important effect of carbohydrate retention on plaque pH response.

Acids↗

[Biologically active substances isolated from Hypericum attenuatum Choisy].

Four dianthrones, two oxymethylanthraquinones, two reductive forms of anthraquinones and five flavonoids have been isolated from the plant source Hypericum attenuatum Choisy (Guttiferae) firstly investigated for these substances contents. Dianthrones pseudohypericin, protohypericin, protopseudohypericin, oxymethylanthraquinones frangulaemodin, frangulin, reductive anthraquinones emodin anthrone, emodin anthranol, and flavonoids quercetin, quercitrin, isoquercitrin, rutin have been identified for the first time. High hyperoside contents in herb of Hypericum attenuatum is established.

Anthracenes↗

[Study of luminescence ability of organic white light emitting diode by light conversion].

An organic luminescence material of white light was investigated. The organic luminescence film was made by heating and melting method. The film consists of riboflavin, anthrone derivative, and linear low-density polyethylene. The results show that the spectra of luminescence films were affected by weight ratio and heating time of the made films. The spectra were wide band from green light to red light. The organic white light emitting diodes made of this film have super performance.

Anthracenes↗

Laxatives and intestinal epithelial cells: a morphological study of epithelial cell damage and proliferation.

Experimental studies indicate that anthranoid laxatives may induce epithelial damage. In addition they induce the release of prostaglandins. Epithelial cell damage and release of prostaglandins are two pathways by which epithelial cell proliferation could be influenced. Other laxatives including fermentable laxatives like lactulose may also influence large intestine cell proliferation by the trophic effect of the fermentation products such as short chain fatty acids. For these reasons an in vitro study was performed on human intestinal epithelial cells in culture to investigate the direct damaging effect of rhein anthrone. Ultrastructural examination showed a dose dependent direct damage. In addition an in vivo study in rats was performed to compare the short and long term effect of sennosides, bisacodyl, sodium picosulphate and lactulose on epithelial cell proliferation in the ileum and large intestine. Cell proliferation was examined by the BrdUrd labeling technique after 2, 6 and 12 weeks of continuous treatment. Studies in control animals show that the Labeling Index (LI) is higher in the caecum compared with other segments of the colon, and higher in the ileum than in the colon. Treatment with sennosides, bisacodyl and sodium picosulphate does not influence the LI in the ileum and induces no statistically significant increase of the LI when the treated groups are compared with the control group at the end of the study. The proliferative pattern along the crypts remains unchanged with all the laxatives throughout the study. It appears therefore that 'contact' laxatives have no major influence on ileal and colonic epithelial cell proliferation.

Animals↗

Quantification of fecal carbohydrates by near-infrared reflectance analysis.

Established methods for quantitative analysis of fecal carbohydrates (CHO) are time consuming, require unpopular sample handling, and are therefore rarely performed. The aim of this study was to evaluate the efficiency, validity, and practicability of near-infrared reflectance analysis (NIRA), compared with standard methods for measurement of fecal CHO. Excretion of fecal CHO was cross- validated spectrophotometrically with the anthrone method. Fecal CHO concentrations ranged form 2.7 to 24.5 g/kg wet weight. Methods comparison showed linear regression over the entire range of diagnostic relevance with a correlation coefficient of 0.869 (S(y/x) +/- 0.31). Repeated measurements from the same stool collections obviated the need for homogenization. These results indicate that NIRA may be a new, reliable, and accurate test in the diagnosis of CHO malabsorption.

Adolescent↗

[The mechanism of action of sennosides].

A review of the recent progress in the study of the mode of action of the sennosides, the active constituents of the senna drug, is presented. An interaction between rhein anthrone, the active metabolite of the sennosides, and the immune cells of the colon is suggested as a base for laxative activity.

Animals↗

Skin tumorigenesis by initiators and promoters of different chemical structures in lines of mice selectively bred for resistance (Car-r) or susceptibility (Car-s) to two-stage skin carcinogenesis.

Carcinogenesis-resistant (Car-R) and carcinogenesis-susceptible (Car-S) mice were obtained applying a bi-directional selective breeding approach to a two-stage skin carcinogenesis protocol, using 9,10-dimethyl-1,2-benzanthracene (DMBA) as initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as promoter. Sixteen generations of selection produced a remarkable interline difference in responsiveness to two-stage skin carcinogenesis between Car-R and Car-S: identical DMBA (25 microgram) and TPA (5 microgram) doses induced papillomas in 100% of Car-S compared with 3.3% of Car-R mice and maximal responses of 14.3 or 0.03 papillomas/mouse, respectively, despite the shorter promotion applied to Car-S (49 vs. 208 days). To define the factors determining this great difference, Car-R and Car-S mice were challenged by initiators/promoters chemically unrelated to those used for selection. Both lines were subjected to either initiation by N-methyl-N-nitrosourea (MNU) followed by TPA promotion, or promotion by benzoyl peroxide, or 1,8-dihydroxy-3-methyl-9-anthrone (chrysarobin) following DMBA initiation. Initiation with MNU induced a 10-fold tumour incidence in Car-S compared with Car-R mice, and a 32-fold difference in tumour induction rate. The 2 lines also differed markedly in susceptibility to benzoyl peroxide promotion: Car-S mice initiated with 25 microgram DMBA and promoted with 7.5 mg benzoyl peroxide showed a 12-fold tumour incidence and a 103-fold tumour induction rate compared with the corresponding Car-R group. Both lines, however, were refractory to chrysarobin promotion. The progression of papillomas to carcinomas was examined in all Car-S groups. The incidence of mice that developed carcinomas was 57% in MNU-initiated mice. Benzoyl peroxide was also able to promote carcinoma development in Car-S mice, though with a lower incidence (30.4%) than TPA.

9,10-Dimethyl-1,2-benzanthracene↗

Anthralin derivatives--inhibition of 5-lipoxygenase--antipsoriatic efficacy.

Inhibition of 5-lipoxygenase by anthralin (1) and 41 derivatives is determined: the acids 38 and 39, the lactones 40-42 and 9-anthrone (8) are the most potent inhibitors, the lactone 41 reaching the efficacy of nordihydroguaiaretic acid (NDGA). The results were correlated with the hydrophilic/lipophilic balance of the test compounds and their clinical efficacy as far as known. There is no correlation between the "minimum structure" of Krebs and Schaltegger concerning antipsoriatic activity and the inhibitory effects against 5-lipoxygenase.

Animals↗

Anthralin: chemical instability and glucose-6-phosphate dehydrogenase inhibition.

The chemical stability of the antipsoriatic drug, anthralin (1,8-dihydroxy-9-anthrone), in solution has been studied using high-performance liquid chromatographic analysis. The time course for decomposition in solution has been correlated with that of the inhibition of glucose-6-phosphate dehydrogenase, one of the most widely documented biochemical properties associated with anthralin. Solutions of anthralin in aqueous buffer (37 degrees, pH 7.5, under light protection) completely within 4 hr giving the 10,10'-dimer (40%), no detectable 1,8-dihydroxy-9,10-anthraquinone, and a greatly increased potency of inhibition of glucose-6-phosphate dehydrogenase. This increased inhibitory potency could not be explained by formation of the dimer which, like anthralin and its quinone, were shown to be only weak inhibitors of the enzyme. In acetone solution exposed to light and air, anthralin decomposed completely within 4 days, in part via the dimer as intermediate. The final solution had the characteristic color of anthralin-brown, contained the quinone (20%), and like decomposed aqueous solutions of anthralin, completely inhibited glucose-6-phosphate dehydrogenase. The results show that neither anthralin, nor either of its two identified decomposition products, is the potent toxic species against glucose-6-phosphate dehydrogenase.

Acetone↗