Alternate Pathways of Steroid Biosynthesis and the Origin, Metabolism, and Biological Effects of Ring B Unsaturated Estrogens
Ronald Hobkirk in Steroid Biochemistry, 1979
To assist in the identification of the metabolites represented by the radioactivity found in the urine, three males ingested large amounts of nonradioactive equilin and 3-day combined urine collections were partitioned as described before (Figure 14). The phenolic fractions from this urine were added to those from the urine collected in the earlier experiment in which the 6,9-3H-equilin was given as a single bolus. The combined extracts were purified on a 600-g Celite® partition column using the system heptane: benzene: methanol: water (10:5:8:2). The pattern of radioactivity found in the column fractions is shown in Figure 25. A small amount of radioactive material was found in fractions 300 to 400 from which equilin and equilenin were isolated and identified. No radioactivity was found in the position of 17α-dihydroequilin, but a relatively large amount was found in the position of 17β-dihydroequilin and 17β-dihydroequilenin. The largest portion of the radioactive material was found in fractions 1500 +, indicating that it consists of a very polar compound or group of compounds. In contrast, the pregnant mare does not metabolize equilin to materials more polar than dihydroequilin or dihydroequilenin (Figure 26). Other differences in the metabolites found in the mare include the presence of a large amount of nonreduced equilin and a significant amount of 17α-dihydroequilin. From the human urine, equilin, equilenin, 17β-dihydroequilin, and 17β-dihydroequilenin have been isolated and their radiochemical purity established (Table 20).
The Diagnosis and Management of Lipoprotein Disorders
Jack L. Leahy, Nathaniel G. Clark, William T. Cefalu in Medical Management of Diabetes Mellitus, 2000
Pravastatin therapy is usually started at 10 or 20 mg daily at bedtime, and can be increased to 40 mg. Its structure is similar to lovastatin, except it is given as the open acid form and has a hydroxyl group attached to it, making it a more polar compound with greater liver selectivity. It is a fungal metabolite, and is produced by fermentation. It was approved in the United States in 1991. It has been successfully given in combination with gemfibrozil as well as with cyclospo- rine. Pravastatin at 40 mg/day has been reported to lower LDL-C 28%, total mortality 46%, fatal and nonfatal CHD 62%, and stroke 62% in over 1800 patients with atherosclerosis (PLAC I, PLAC II; REGRESS, KAPS) (14). Pravastatin at 40 mg/day reduced LDL-C 26%, total mortality 22%, fatal and nonfatal myocardial infarction (MI) 31%, and need for angioplasty or bypass surgery 37% in middle- aged men with moderate hypercholesterolemia without documented CHD in the large (n = 6595) prospective West Scotland Study (32). Pravastatin at 40 mg/day lowered LDL-C 26%, fatal and nonfatal MI 24%, bypass 26%, angioplasty 23%, fatal MI 37%, and stroke 31% in post-MI patients with LDL cholesterol values in the range of 115-174 mg/dL, (mean 137 mg/dL) in the Cholesterol and Recurrent Events (CARE) trial (n = 4159) (30). This study also indicated no significant benefit if baseline LDL-C values were less than 125 mg/dL, with no significant benefit on total mortality. In the large prospective Australian LIPID trial, 9013 men and women with CHD with total cholesterol values between 155 and 271 mg/dL were randomized to pravastatin 40 mg/day or placebo. Total, CHD, and stroke mortality were significandy reduced by 23,24, and 20% in the drug group versus the placebo group (24).
Local Anesthetics and Additives
Bernard J. Dalens, Jean-Pierre Monnet, Yves Harmand in Pediatric Regional Anesthesia, 2019
Morphine-6-glucuronide is a minor metabolite in man under normal circumstances, but it has been reported to produce prolonged analgesic effects in animals when injected by various routes (including systemic administration).128 Both morphine-3-glucuronide and morphine-6-glucuronide are able to produce narcotic effects when they are injected directly into the central nervous system.128 This must be kept in mind when high blood levels of drug are maintained for long periods, since even the most polar compound can penetrate any membrane barrier, including the blood/brain barrier.
An Investigation of the Antiproliferative Effect of Rhododendron luteum Extract on Cervical Cancer (HeLa) Cells via Nrf2 Signaling Pathway
Published in Nutrition and Cancer, 2022
Ibrahim Turan, Selim Demir, Serap Ozer Yaman, Deniz Canbolat, Ahmet Mentese, Yuksel Aliyazicioglu
A 2′‑7′‑dichlorodihydrofluorescein diacetate (H2DCFDA) fluorescent probe was used to measure the intracellular generation of ROS (31). This probe is a stable and non-polar compound capable of easy dispersion into cells. After the probe enters the cell, the acetate groups in the structure are cut by intracellular esterases, and the resulting DCFDA is trapped in the cells (32). When DCFDA interacts with ROS within the cell, it emits a highly fluorescent radiance. The intensity of the fluorescence intensity is therefore proportional to the amount of ROS produced in the cells (31, 32). Whether the RLE has the potential to generate ROS in the HeLa cells was evaluted using the fluorometric method. HeLa (5 × 103 cells/well) cells were seeded into a black-walled 96-well cell culture plate and were allowed to attach overnight. The cells were then incubated with various concentrations of RLE (10–40 µg/mL) for 12 h, followed by washing with phosphate buffer saline and loading with 10 µM H2DCFDA for 30 min. Treatment of 1 mM H2O2 for 30 min was used as a positive control. ROS generation was quantified using a plate reading fluorometer (Molecular Devices SpectraMax Paradigm Multi-Mode, Sunnyvale, CA, USA; ex: 480 nm, em: 530 nm), and the results were expressed as relative ROS production compared to untreated control cells (31).
Micellar solubilization of poorly water-soluble drugs: effect of surfactant and solubilizate molecular structure
Published in Drug Development and Industrial Pharmacy, 2018
Zahari Vinarov, V. Katev, D. Radeva, S. Tcholakova, N. D. Denkov
Therefore, the major aim of this article is to clarify the link between the surfactant molecular structure and drug solubilization capacity by studying systematically the effect of 19 different surfactants on the solubility of two hydrophobic drugs of different polarity: fenofibrate and danazol. These two drugs were chosen as they both have solubility-limited absorption (BCS class II) and have similar molecular mass (361 and 338 g/mol for fenofibrate and danazol, respectively), which allows us to compare the effect of drug molecular structure on micellar solubilization. In addition, the model non-polar compound androstane was also studied to clarify the specific role of the ion–dipole interactions for the solubilization capacity of charged surfactant micelles. To gain additional information about the drug–surfactant interactions, the locus of fenofibrate solubilization inside the micelles of different surfactants was studied by UV absorption spectroscopy.
Composition of aerosols from thermal degradation of flavors used in ENDS and tobacco products
Published in Inhalation Toxicology, 2022
Philip J. Kuehl, Jacob D. McDonald, Derek T. Weber, Andrey Khlystov, Matthew A. Nystoriak, Daniel J. Conklin
Filters and XAD-4 resin were loaded together into accelerated solvent extractor (ASE, Dionex, Sunnyvale, CA) cells and spiked with the following deuterated internal standards: naphthalene-d8, biphenyl-d10, acenaphthene-d10, phenanthrene-d10, anthracene-d10, pyrene-d12, benz(a)anthracene-d12, chrysene-d12, benzo(k)fluoranthene-d12, benzo(e)pyrene-d12, benzo(a)pyrene-d12, perylene-d12, benzo(ghi)perylene-d12 coronene-d12, hexanoic-d11 acid, succinic-d4 acid, decanoic-d19 acid, adipic-d10 acid, suberic-d12 acid, homovanillic-2,2-d2 acid, myristic-d27 acid, heptadecanoic-d33 acid, oleic-9,10-d2 acid, and tetradecanedioic-d24 acid (CDN Isotopes, Quebec, Canada) and benzoic-d5 acid, levoglucosan-d7, and cholesterol-2,2,3,4,4,6-d6 (Cambridge Isotope Laboratories, Inc., Andover, MA, USA) Parameters for ASE extraction were: temperature: 80 °C, solvents: 150 mL of dichloromethane followed by 150 mL of acetone, pressure: 1500 psi, extraction time for each solvent: 15 min. After extraction, samples were pre-concentrated to 1 mL with a rotary evaporator (Rotavapor R-124, BÜCHI, New Castle, DE, USA ) under gentle vacuum at 35 ± 2 C. The extracts were then filtered with a 0.2-µm pore size polytetrafluoroethylene membrane syringe filters (Whatman, Florham Park, NJ, USA), and transferred into 2-mL volume amber glass vials. The extracts were split into two parts for PAH and polar compound analysis.
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