Prediction of aqueous solubility of heteroatom-containing organic compounds from molecular structure.

The use of quantitative structure-property relationships (QSPRs) to predict aqueous solubilities (log S) of heteroatom-containing organic compounds from their molecular structure is presented. Three data sets are examined. Data set 1 contains 176 compounds having one or more nitrogen atoms with some oxygen (log S[mol/L] range is -7.41 to 0.96). Data set 2 contains 223 compounds having one or more oxygen atoms, with no nitrogen (log S[mol/L] range is -8.77 to 1.57). Data set 3 contains all 399 compounds from sets 1 and 2 (log S/mol/L] range is -8.77 to 1.57). After descriptor generation and feature selection, multiple linear regression (MLR) and computational neural network (CNN) models are developed for aqueous solubility prediction. The best results were obtained with nonlinear CNN models. Root-mean-square (rms) errors for training with the three data sets ranged from 0.3 to 0.6 log units. All models were validated with external prediction sets, with the rms errors ranging from 0.6 log units to 1.5 log units.

Worker dose analysis based on real time dosimetry.

Real time dosimetry was used to analyze nuclear medicine technologist dose from performing positron emission tomography clinical imaging procedures. The purpose was to identify which tasks in the procedure were the greatest contributors to dose. Results identified the patient positioning task as the single largest source of technologist dose, followed by measurement and administration of the radioactive drug. The dosimetry method appears suitable for any work situation where it is not clear whether task modification or installation of shielding will better reduce worker dose.

Contractility of intrarenal arteries in Goldblatt hypertensive rabbits.

The present investigation contractile responses of microdissected intrarenal arcuate arteries from sham-operated rabbits and two-kidney, one clip Goldblatt hypertensive rabbits at 2 and 12 weeks after procedure. Arcuate arteries from both kidneys of the sham-operated rabbits and stenotic and nonstenotic kidneys of the Goldblatt hypertensive rabbits were studied. Mean arterial blood pressures of the sham-operated and Goldblatt hypertensive rabbits were 72 +/- 2 and 85 +/- 2, and 130 +/- 3 and 125 +/- 4 mm Hg at 2 weeks and 12 weeks, respectively. In vitro isometric contractile force measurements were made with a small-artery myograph. Responses to graded concentrations of norepinephrine were evoked in the arcuate arteries, and the maximum active force was developed and -log EC50 was determined. At 2 weeks after procedure, the maximum responses of the vessels from the left kidney of the sham-operated rabbits and those from the stenotic left kidney of the Goldblatt hypertensive rabbits did not differ. The responses of the vessels from the right kidney of the sham-operated rabbits did not differ from those of the nonstenotic right kidney of the hypertensive rabbits. A markedly depressed maximum response of the vessels from the nonstenotic kidney of the hypertensive as compared with the right kidney of the sham-operated rabbits was found at 12 weeks after procedure, whereas the vessels from the stenotic kidney of the hypertensive and the left kidney of the sham-operated rabbits exhibited almost identical maximal responses. Responses to U 46619 were similarly affected in the two groups of rabbits. Cold-induced contractile responses of the arcuate arteries from the nonstenotic kidney of the hypertensive rabbits did not differ from those of the sham-operated rabbits at the 12-week interval.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of intrarenal arterial adrenergic receptors in renovascular hypertension.

alpha-Adrenergic receptor subtypes were investigated using [3H]prazosin, an alpha 1 selective antagonist, and the alpha 2 selective antagonist [3H]rauwolscine in a smooth muscle plasma membrane enriched microsomal fraction prepared from rabbit intrarenal arterial vasculature. Both radioligands displayed single components on Scatchard analysis. The specific binding of [3H]prazosin was of high affinity (0.54 +/- 0.04 nM) with a maximum binding capacity (Bmax) of 212 +/- 15 fmol/mg protein. The maximum number of [3H]rauwolscine binding sites was 64 +/- 4 fmol/mg of protein with a dissociation constant (Kd) of 5.60 +2- 0.27 nM. Binding of both radioligands was rapid, saturable, and specific. alpha 1- and alpha 2-adrenergic receptors in the intrarenal arterial membrane preparation were also characterized at 2-, 4-6-, and 10-12-week intervals during the course of development and maintenance of chronic two-kidney, one clip (2K1C) Goldblatt hypertension and in age-matched sham-operated normotensive control rabbits. The alpha 1-adrenergic receptor affinity for [3H]prazosin binding in hypertensive rabbits was significantly increased in the stenotic, but not contralateral, kidney at 2 weeks; however, at 6 weeks the receptor affinity of both kidneys was significantly increased compared with those of the normotensive control group. No difference in alpha 1-adrenergic receptor affinity was seen at 12 weeks, and there were no changes in Bmax at any of the weekly intervals. Neither the Kd, nor Bmax, for [3H]rauwolscine in either kidney showed a significant difference between hypertensive rabbits and normotensive control rabbits. These studies demonstrate the existence in the rabbit intrarenal arterial vasculature of binding sites with alpha 1- and alpha 2-adrenergic receptor specificity.(ABSTRACT TRUNCATED AT 250 WORDS)