Longitudinal Psychological Distress After Malignant Brain Tumor Diagnosis: A Multilevel Analysis of Patients and Their Caregivers.

Objective: Malignant brain tumors are associated with debilitating symptoms and a poor prognosis, resulting in high psychological distress for patients and caregivers. There is a lack of longitudinal studies investigating psychological distress in this group. This study evaluated fear of progression (FoP), anxiety and depression in patients and their caregivers in the 6 months following malignant brain tumor diagnosis.

Asymmetric transfer hydrogenation of 1-naphthyl ketones by an ansa-Ru(II) complex of a DPEN-SO2N(Me)-(CH2)2(η(6)-p-Tol) combined ligand.

The first second-generation designer Ru(II) catalyst 1b featuring an enantiopure N,C-(N-ethylene-N-methyl-sulfamoyl)-tethered (DPEN-κ(2)N,N')/η(6)-toluene hybrid ligand is introduced. Using an S/C = 1000 in HCO2H-Et3N 5:2 transfer hydrogenation medium, secondary 1-naphthyl alcohols are obtained in up to >99.9% ee under mild conditions.

In-line reaction monitoring of entacapone synthesis by Raman spectroscopy and multivariate analysis.

In-line Raman spectroscopy and multivariate analysis were used to monitor Knoevenagel condensation reaction, the final step in preparation of drug entacapone. By applying a fiber optical Raman probe immersed into a reaction vessel Raman spectra of the reaction mixture were recorded in situ during the entacapone synthesis in toluene, heptane and isobutyl acetate. Due to the complexity of the measured spectra, the obtained data were analyzed and interpreted by means of principal component analysis.

Sphingolipid bases. A revisitation of the O-methyl derivatives of sphingosine. Isolation and characterization of diacetate derivatives, with revised 13C nuclear magnetic resonance assignments for D-erythro-sphingosine.

As described by Carter et al. (J. Biol.

Inhibitors of sterol synthesis. Metabolism-based design and construction of a new analog of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one and its effects in cultured mammalian cells and in rats.

3 beta-Hydroxy-5 alpha-cholest-8(14)-en-15-one (I) is a potent regulator of cholesterol metabolism. In the present study, the 7 alpha-methyl-25,26,26,26,27,27,27-heptafluoro analog (X) of I has been synthesized with the goal of blocking not only the side chain oxidation of I but also its conversion to cholesterol. X was prepared in seven steps from the known 7 alpha-methyl analog (IX) of I.

Inhibitors of sterol synthesis. Effects of a new fluorinated analog of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one in rats.

3 beta-Hydroxy-25,26,26,26,27,27,27-heptafluoro-5 alpha-cholest-8(14)-en-15-one (VII), an analog of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one (I) in which conversion to 26- and 25-oxygenated metabolites is blocked by the F7-substitution, was administered to male Sprague-Dawley rats at levels of from 0.025 to 0.15% by weight in a ground chow diet.

Inhibitors of sterol synthesis: effects of a 7 alpha-alkyl analog of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in cultured mammalian cells and on serum cholesterol levels and other parameters in rats.

The 7 alpha-methyl analog (II) of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15- one (I) was prepared by chemical synthesis and evaluated with respect to its effects on HMG-CoA reductase activity in CHO-K1 cells and on serum cholesterol levels in rats. The 7 alpha-methyl substitution had no detectable effect on the potency of I in lowering HMG-CoA reductase activity in the cultured cells. In contrast, the 7 alpha-methyl substitution had a marked effect on the action of I in the suppression of food consumption in rats.

Inhibitors of sterol synthesis. Tritium-labeled 26-hydroxycholesterol of high specific activity from a byproduct of the Clemmensen reduction of diosgenin.

(25R)-26-Hydroxycholesterol (I) was synthesized in six steps from (22Z,25R)-cholesta-5,22-diene-3 beta,26-diol (II) in 31% overall yield. The 26-tert-butyldiphenylsilyl ether of II was converted via its 3 beta-tosylate to (22Z,25R)-6 beta-methoxy-26-(tert- butyldiphenylsilyloxy)-3 alpha,5-cyclo-5 alpha-cholest-22-ene (V). Removal of the 26-silyl group of V gave (22Z,25R)-6 beta-methoxy-3 alpha,5-cyclo-5 alpha-cholest-22-en-26-ol, which was hydrogenated over platinum oxide and then hydrolyzed to I.

D-erythro-sphingosine lowers 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in Chinese hamster ovary cells.

D-Erythro-sphingosine lowered the levels of HMG-CoA reductase activity in CHO-K1 cells. Significant suppression of reductase activity was observed at 5 microM, 10 microM, and 15 microM concentrations of the sphingolipid base and approximately 50% lowering was found at 10 microM. In contrast, L-threo-sphingosine had no effect on the levels of reductase activity under the conditions studied.

Inhibitors of sterol synthesis. Metabolism of [2,4-3H]5 alpha-cholest-8(14)-en-3 beta-ol-15-one after oral administration to a nonhuman primate.

5 alpha-Cholest-8(14)-en-3 beta-ol-15-one is a potent inhibitor of cholesterol biosynthesis which has significant hypocholesterolemic activity upon oral administration to rodents and nonhuman primates. In the present study the metabolism of the 15-ketosterol has been investigated after the oral administration of a mixture of [2,4-3H]5 alpha-cholest-8(14)-en-3 beta-ol-15-one and [4-14C]cholesterol to 8 baboons. Blood samples were obtained at 4, 8, 12, 16, and 24 h after administration of the labeled sterols.

Inhibitors of sterol synthesis. Morphological studies in rats after dietary administration of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one, a potent hypocholesterolemic compound.

The morphological effects of short-term (9 days) dietary administration (0.1% in a laboratory chow diet) of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one, a novel regulator of cholesterol metabolism with significant hypocholesterolemic activity, has been studied in young male rats. Control animals included rats fed the basal diet ad libitum and a series of rats pair-fed to the individual experimental animals.

Concerning the chemical synthesis of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one, a novel regulator of cholesterol metabolism.

A four-step synthesis of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one (I) from 7-dehydrocholesterol is described. This synthesis, which is efficient and suitable for kilogram scale work, was carried out in a 33% overall average yield (39% overall best yield). A major byproduct of the hydrolysis of 3 beta-benzoyloxy-14 alpha,15 alpha-epoxy-5 alpha-cholest-7-ene to I was found to be the ring C aromatic sterol 12-methyl-18-nor-5 alpha-cholesta-8,11,13-trien-3 beta-ol.

Inhibitors of sterol synthesis. A major role of chylomicrons in the metabolism of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one in the rat.

The metabolism of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one (I), a potent regulator of cholesterol (Chol) metabolism which has significant hypocholesterolemic activity upon oral administration to animals, has been investigated in male rats. After intragastric administration of [2,4-3H] I and [4-14C]Chol in triolein to intestinal lymph duct-cannulated rats, most of the 3H of the lymph was associated with chylomicrons. Most of the 3H in the chylomicrons was associated with fatty acid esters of I and the oleate ester represented the major species of the esters of I.

Inhibitors of sterol synthesis. Metabolism of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one after intravenous administration to bile duct-cannulated rats.

The metabolism of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one has been studied after intravenous administration to bile duct-cannulated rats. Very rapid and substantial conversion of the 15-ketosterol to polar biliary metabolites was observed in both male and female rats. For example, upon intravenous injection of [4-14C]5 alpha-cholest-8(14)-en-3 beta-ol-15-one to male bile duct-cannulated rats, approximately 86% of the administered 14C was recovered in bile in the first 38 h.

Inhibitors of sterol synthesis. Metabolism of [2,4-3H]5 alpha-cholest-8(14-)-en-3 beta-ol-15-one after intravenous administration to a nonhuman primate.

The metabolism of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one, a potent inhibitor of cholesterol synthesis with marked hypocholesterolemic activity, has been studied after the intravenous administration of a mixture of [2,4-3H]5 alpha-cholest-8(14)-en-3 beta-ol-15-one and [4-14C] cholesterol to a baboon. The levels of 3H in plasma which was associated with the free 15-ketosterol decreased very rapidly (T1/2 approximately 9 min) after injection of the labeled sterol. By 4 h, the level of the [3H]15-ketosterol in plasma was negligible.

Inhibitors of sterol synthesis. Effect of dietary 5 alpha-cholest-8(14)-en-3 beta-ol-15-one on ACAT activity of jejunal microsomes of the rat.

Dietary administration (0.1% in a chow diet for 8 days) of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one, a potent inhibitor of sterol biosynthesis with marked hypocholesterolemic action, to rats caused a 77% reduction in the levels of acyl co-enzyme A:cholesterol acyl transferase activity of jejunal microsomes relative to those observed in pair-fed control animals. No differences were observed in mean levels of cholesterol concentration in jejunal microsomes of experimental and pair-fed control animals.

5 alpha-Cholest-8(14)-en-3 beta-ol-15-one. In vivo conversion to cholesterol upon oral administration to a nonhuman primate.

The metabolism of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one (I), a potent inhibitor of cholesterol synthesis with marked hypocholesteremic activity, has been studied in a nonhuman primate. A mixture of [2,4-3H]-I and [4-14C]-cholesterol was administered to a male baboon in the form of a feedball. Blood was samples at 4, 8, 12, 16, and 24 hr.

Inhibitors of sterol synthesis. Dietary administration of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one inhibits the intestinal absorption of cholesterol in lymph-cannulated rats.

The effect of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one, a potent inhibitor of cholesterol synthesis with marked hypocholesterolemic activity, on the intestinal absorption of exogenous cholesterol has been studied in lymph-cannulated rats. Administration of the 15-ketosterol at a level of 0.05% in a rat chow diet for 10 days was associated with a marked decrease (-64%) in the absorption of cholesterol.

5 alpha-Cholest-8(14)-en-3 beta-ol-15-one lowers serum cholesterol and induces profound changes in the levels of lipoprotein cholesterol and apoproteins in monkeys fed a diet of moderate cholesterol content.

5 alpha-Cholest-8(14)-en-3 beta-ol-15-one has been found to have significant hypocholesterolemic activity upon oral administration at a daily dosage of 75 mg/kg of body weight to Rhesus monkeys fed a diet of moderate cholesterol (Chol) content [0.19 mg/kcal (1 cal = 4.184 J) of diet].

5 alpha-Cholest-8(14)-en-3 beta-ol-15-one, a potent inhibitor of sterol biosynthesis, lowers serum cholesterol and alters distributions of cholesterol in lipoproteins in baboons.

5 alpha-Cholest-8(14)-en-3 beta-0l-15-one has been found to have significant hypocholesterolemic action on oral administration to baboons at dosages of 50 and 75 mg/kg of body weight. The 15-ketosterol decreased the levels of total serum cholesterol and low density lipoprotein plus very low density lipoprotein (LDL/VLDL) cholesterol and the percentage of total cholesterol associated with LDL/VLDL and increased the percentage of total cholesterol associated with high density lipoprotein (HDL). Moreover, administration of the steroid was associated with an absolute increase in the concentration of HDL cholesterol in those animals with low HDL levels (or with a low percentage of total serum cholesterol in the HDL fraction.

Sterol synthesis: a simple method for the isolation of zymosterol (5 alpha-cholesta-8, 24-dien-3 beta-ol) from yeast and spectral properties of zymosterol.

A relatively simple method is described for the isolation of zymosterol (5 alpha-cholesta-8, 24-dien-3 beta-ol) of high purity from baker's yeast. Also presented are detailed spectral properties, including 13C NMR spectral analyses, of zymosterol and its acetate derivative.

Isolation of a novel lipid hapten, cytolipin S, from rat spleen.

Antisera against rat erythrocytes contain agglutinins directed against unknown lipid determinants. Complement-fixation shows more reactivity with lipid extracts of rat spleen than of other rat tissues. The isolation of the reactive lipid from rat spleen, cytolipin S, is described.