The disposition of the enantiomers of oxaprotiline has been investigated after single 100 mg oral doses of racemic 14C-labelled oxaprotiline X HCl in two healthy subjects. Absorption was complete. Peak blood concentrations of total 14C were 804 and 1010 ng equiv. g-1 after 4-6 h in the two subjects. After 9 days 85 and 80 per cent of the dose were excreted in urine, and a total of 93 and 87 per cent were found in the excreta. Mean peak blood concentrations of unchanged S(+)- and R(-)-oxaprotiline amounted to 25 and 10 ng g-1 before, and 474 and 422 ng g-1 after acid hydrolysis (free plus O-glucuronide). The mean blood half-lives of the S(+) and R(-) isomers were 22 and 23 h. Direct O-glucuronidation is the major metabolic pathway and N-demethylation a minor one. The former is more marked with the S(+) isomer and the latter with the R(-) isomer. For oxaprotiline, the AUC-ration of S(+) to R(-) was 2.2 before and 1.4 after hydrolysis. For desmethyl oxaprotiline the corresponding ration was 0.8 after hydrolysis. In urine, 0.8 and 0.5 per cent of total 14C were present as unchanged S(+)- and R(-)-oxaprotiline. After acid hydrolysis of the O-glucuronides, the enantiomers account for 44.7 and 37.1 per cent. The O-glucuronides of S(+)- and R(-)-desmethyl oxaprotiline account for 4.6 and 5.7 per cent.
We developed a two-site chemiluminescence immunoassay for human vascular endothelial growth factor (VEGF). The assay recognized both VEGF121 and VEGF165 isoforms, but had no detectable cross-reactivity with platelet-derived growth factor or placenta growth factor. The range of detection was between 30 ng/L and 30 micrograms/L VEGF. Inter- and intraassay variations were 8.2-8.3% and 7.2-7.6%, respectively. VEGF concentrations were measured in the cytosolic extracts of 45 ovarian and 142 primary breast tumors. The amount of VEGF in the ovarian tumors (median = 0.46 ng/mg total protein, range 0-15.8 ng/mg) was significantly (P = 0.03) higher compared with the breast tumors (median = 0.24 ng/mg total protein, range 0-12.3 ng/mg). In 32 and 7 extracts of normal breast tissues adjacent and distant to the tumors, respectively, VEGF concentrations were significantly much lower (P < 0.0001). The detection of substantial amounts of VEGF in two invasive tumors (compared with normal tissues) suggests that the assay should be a useful tool for investigating the prognostic value of VEGF in breast and ovarian carcinomas and for selecting patients for future anti-VEGF therapy.
To quantitatively determine tricyclic antidepressant agents, we used a combined gas chromatograph/mass spectrometer system, and deuterium-labeled internal standards. Recovery exceeds 95% and the coefficient of variation is less than 4% for human whole-blood samples supplemented with 5 to 15 ng of clomipramine hydrochloride or 20 to 60 ng of dehydroimipramine hydrogen fumarate per milliliter. For both amines, the detection limit is 0.3 mug/liter; Six healthy volunteers who received a single oral dose of 50 mg of clomipramine hydrochloride showed peak drug concentrations in the blood 3 to 5 h after administration, ranging between 14.4 and 30.1 mug/liter. Plasma/whole blood concentration ratios varied from 0.70 to 1.20, and the cumulative renal elimination from 0 to 72 h is less than 0.2% of the dose. This method is suitable for in vivo bioavailability studies of unchanged clomipramine, dehydroimipramine, and imipramine after a single oral dose of as little as 25 mg.
This case report illustrates the presence of intranodal thyroid tissues in ipsilateral cervical lymph nodes after hemithyroidectomy for multinodular goiter in an adolescent patient. It highlights the rare radiological finding of thyroid tissues within cervical lymph nodes detected by ultrasonography and computed tomography, which is a great mimicker of nodal metastasis.
1. The disposition and metabolism of oxprenolol have been investigated in two healthy male volunteers, following a single 160 mg oral dose of racemic 14C-labelled oxprenolol.2. Absorption was rapid and complete. Peak blood concentrations of total radioactivity were 8.83 and 8.21 nmol.g−1 after 1 and 1.5 h in the two subjects. After 4 days 93.4 and 81.90% of the dose was excreted in urine, and a total of 96.6 and 84.5% found in the excreta.3. Mean peak blood concentrations of unchanged R(+)—and S(—)—oxprenolol were 0.83 and 0.81 nmol.g−1. Maximal concentrations of the glucuronides of the R(+)—and S(—)—isomers were 1.98 and 3.51 nmol.g−1. The mean half-lives of both oxprenolol enantiomers were 1.8 h, those of their glucuronides were 3.2h (R(+)) and 4.6h (S(—)).4. Unchanged oxprenolol and the oxprenolol glucuronides constituted 11.4 and 66.5% of the area under the blood concentration-time curve (AUC, 0–24 h) of total radioactivity. The AUC-ratio of R(+) to S(—) was 1.19 for free oxprenolol and 0–36 for the glucuronides. Free metabolites II-X represented together 4.3% of 14C-AUC, and their glucuronides 15.2%.5. In urine, 1.8 and 1.0% of the total radioactivity was present as unchanged R(+)—and S(—)—oxprenolol, respectively. The glucuronides of the enantiomers accounted for 24.5 and 26.5%. The percentages of free 4- and 5- hydroxy oxprenolol were 0.7 and 2.4% while those of their glucuronides were 12.3 and 7.5%. Metabolites IV-X constituted together 6.2% in free form and 5.3% in conjugated form.6. In conclusion, the good mass balances in blood and urine has enabled the comprehensive and quantitative description of the metabolic fate of oxprenolol in man. Oxprenolol is extensively metabolized, direct O-glucuronidation being the major metabolic pathway and oxidative reactions minor ones. The disposition of the oxprenolol enantiomers revealed no remarkable stereoselective differences.
This case report presents serous atrophy of bone marrow (SABM) in a cachexic patient with metastatic squamous cell carcinoma who had undergone radiotherapy. The unique magnetic resonance imaging (MRI) findings of SABM, known as the “flip-flop” phenomenon, were observed in both the irradiated and nonirradiated areas, a finding previously unreported in the literature. The report highlighted the characteristic features of SABM in various MRI sequences, which can be easily misinterpreted as technical errors, leading to unnecessary repetition of MRIs.
Abstract The reaction of CO 2 with GRIGNARD reagents carrying an ether grouping in a sterically suitable position can be directed to afford predominantly either the carboxylic acid or the symmetrical ketone. Thus, the magnesiumorganic compounds prepared from chloromethyl‐methyl ether, benzyl‐chloromethyl ether and 2‐methoxy‐bromobenzene, upon treatment with CO 2 under appropriate conditions give the corresponding ketones in excellent yield. An attempt is made to rationalize this finding from a mechanistic viewpoint. The easily accessible 1,3‐bis(benzyloxy)‐acetone represents a convenient intermediate for an efficient and simple synthesis of glycerol.
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