The binding of purified, ferritin-labeled soybean seed lectin to the cell surfaces of Rhizobium japonicum 31 lb 138 has been examined by whole mount, thin section, and freeze-etch electron ...microscopy. The ferritin-labeled lectin binds in a biochemically specific manner to the capsular material of this bacterium. The lectin does not bind to the outer membranes of the cells or to flagella. Labeled lectin binds to sites throughout the capsular structure, although the density of labeling is somewhat greater on the outer surface of the capsule. Some cells appear to be partially encapsulated. Preservation of the capsular material proved difficult, and methods for retaining most of the capsular material were developed.
Our search for water-soluble quinazoline TS inhibitors that are transported into cells via the RFC, but are not substrates for FPGS, led us to the synthesis of dipeptide analogues of ICI 198583 ...diglutamate. Although a number of dipeptide analogues were active against isolated TS and L1210 cells in vitro, lack of in vivo stability was a problem. This was circumvented by the synthesis of modified dipeptides where either the alpha-carboxyl of the second amino acid was removed (alpha'-COOH) e.g. -L-glu-GABA or where the second amino acid was the unnatural D-enantiomer e.g.-L-glu-D-glu. Further studies were performed with the -L-glu-D-glu and its 7-CH3, 2'F modified analogue, demonstrating that they use the RFC for cell entry but are not active through polyglutamate formation. The latter compound was tested against experimental tumour models and found to have good activity.
The bioequivalence of etoposide phosphate, a prodrug of etoposide, to etoposide was assessed in a randomized, crossover study in 29 patients with histologically established solid tumors that had ...failed conventional treatment. Cohorts of patients received one treatment course each of etoposide and etoposide phosphate which consisted of a 100 mg/m2 per day etoposide equivalent dose infused i.v. over 1 hr on a Day 1 to 5 schedule of treatment. The second course was administered 21 days later or on recovery of blood cell counts. Plasma and urine samples were collected over 24 hr on Day 1 of each course and assayed for etoposide content by a validated HPLC/UV method. Resulting data were subjected to noncompartmental pharmacokinetic analysis. Hematology profiles were obtained by collecting blood samples prior to the first course and twice a week after each course. The pharmacodynamics and pharmacokinetics of etoposide were virtually identical after the two treatments. The point estimates (90% confidence intervals) for nadir WBC, granulocytes, hemoglobin, and platelets expressed as % decrease from the baseline, and for the pharmacokinetic parameters, Cmax, and AUC0 infinity, after intravenous etoposide phosphate relative to etoposide were 100% (96%, 105%), 97% (91%, 103%), 95% (82%, 109%), 95% (84%, 106%), 107% (101%, 113%), and 113% (107%, 119%), respectively. Therefore, etoposide phosphate is bioequivalent to etoposide based on pharmacokinetic and pharmacodynamic assessments.
Cherts and porcelanites of Late Mesozoic to Cainozoic age, recovered at many sites in all major ocean basins by the Deep Sea Drilling Project, contain both quartz and disordered cristobalite as the ...principal silica phases. The cristobalite is identified as opal-CT and occurs as spherical microcrystalline aggregates of bladed crystals (= lepispheres) that evidently formed by a solution step. This material represents a metastable intermediate stage in the conversion of amorphous biogenous and hydro-thermal silica to quartz. Opal-CT also occurs in siliceous formations on land, both sedimentary and volcanic, but only in those of post-Jurassic ages. Many older cherts now composed entirely of quartz may also have formed from such an intermediate phase but all traces of such a precursor have been removed by recrystallization.
1 The disposition of cyclophosphamide was investigated in a group of myeloma patients. 2 Marked changes in clearance and volume of distribution of cyclophosphamide occurred between investigations. 3 ...The observed changes in disposition did not correlate with biochemical estimates of renal and hepatic function or plasma protein status.
Guanabenz (2,6-dichlorobenzylidene-amino-guanidine) is a centrally acting antihypertensive drug whose mechanism of action is via alpha2 adrenoceptors or, more likely, imidazoline receptors. Guanabenz ...is marketed as an antihypertensive agent in human medicine (Wytensin tablets, Wyeth Pharmaceuticals). Guanabenz has reportedly been administered to racing horses and is classified by the Association of Racing Commissioners International as a class 3 foreign substance. As such, its identification in a postrace sample may result in significant sanctions against the trainer of the horse. The present study examined liquid chromatographic/tandem quadrupole mass spectrometric (LC-MS/MS) detection of guanabenz in serum samples from horses treated with guanabenz by rapid i.v. injection at 0.04 and 0.2 mg/kg. Using a method adapted from previous work with clenbuterol, the parent compound was detected in serum with an apparent limit of detection of approximately 0.03 ng/ml and the limit of quantitation was 0.2 ng/ml. Serum concentrations of guanabenz peaked at approximately 100 ng/ml after the 0.2 mg/kg dose, and the parent compound was detected for up to 8 hours after the 0.04 mg/kg dose. Urine samples tested after administration of guanabenz at these dosages yielded evidence of at least one glucuronide metabolite, with the glucuronide ring apparently linked to a ring hydroxyl group or a guanidinium hydroxylamine. The LC-MS/MS results presented here form the basis of a confirmatory test for guanabenz in racing horses.
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