The estrogenic responses to clomiphene in the different cell types of the rat uterus: morphometrical evaluation

The present study was designed to investigate the dose-response of clomiphene on several estrogenic responses in the immature rat uterus and to compare it to available data on estradiol-17 beta. A dissociation was demonstrated among the different estrogenic responses induced by clomiphene. Very high doses of clomiphene were needed to induce the 6-h uterine eosinophilia and deep endometrial edema, and maximal response levels were not reached at any dose studied. On the contrary, many genomic responses were induced with much lower doses of clomiphene, and maximal response levels were reached with at least the two highest doses of clomiphene. This dissociation is in agreement with the existence of separate groups of responses that are mediated by multiple and independent mechanisms of estrogen action involving different kind of receptors. Luminal epithelial, glandular epithelial, and myometrial hypertrophies were also found to differ with regard to the dose needed to induce this response in each cell type. The dissociation between genomic responses of the different uterine cell types supports the hypothesis of different estrogen receptors for each kind of cell. Clomiphene induces mitoses in the different cell types, but the proportion of mitoses in the cell types was different from that described for estradiol. It is suggested that these differences are also due to differences between receptors involved in cell proliferation.     

Glutamic acid-dihydrogen phosphate hydrogen-bonded networks: their proton polarizability as a function of cations present. Infrared investigations.

Glutamic acid [(L-glu)n] + dihydrogen phosphate systems are studied by infrared (IR) spectroscopy dried and hydrated at 75% relative humidity, as a function of both the phosphate-glutamic acid residue (Pi/glu) ratio and the type of cations present. It is shown that the glutamic acid groups form hydrogen-bonded chains with the phosphates. In these chains the positive charge fluctuates, and they show very large proton polarizability which increases in the series Li+,Na+,K+ systems. These chains are cross-linked via phosphate-phosphate hydrogen bonds, in which the proton is almost localized at one Pi. The comparison of the (L-glu)n + dihydrogen phosphate systems with the results obtained earlier in the case of (L-glu)n + hydrogen phosphate systems shows that the behavior of (L-glu)n + Pi systems strongly depends on the pH. Only with decreasing pH the conducting chains are formed. Finally, a hypothesis is discussed with regard to the charge conduction in the F0 subunit of the H+-ATPase in mitochondria.     

Effect of cycling on final mixed culture fate

Cycling in feed substrate concentration and dilution rate is examined as a means of modifying the final fate of a mixed culture. It is shown for the case where the specific growth rate of one species is always greater than that of the second that no cycling strategy will provide the desired extinction of the faster growing species unless time delay is included in the modeling. To account for the time lag in adjusting organism metabolic activities to environmental changes, an adaptability parameter is introduced. Numerical simulations are carried out and an operating diagram indicating the conditions under which the desired extinction occurs is constructed. Cycling in feed substrate concentration and dilution rate are both found to produce the desired result.     

A model for growth of Saccharomyces cerevisiae containing a recombinant plasmid in selective media

A major problem in the use of plasmids as recombinant vectors is the problem of plasmid-free cell generation from plasmid shedding and subsequent growth. A common technique for controlling the population of plasmidfree cells is the use of selective media against these cells using an auxotrophic host and a plasmid that has the ability to produced the essential metabolite. A distributed model describing the growth of Saccharomyces cerevisiae containing a recombinant plasmid in selective media was developed. The model allows for growth and production of a metabolite by the plasmid-carrying strain and growth of the plasmid-free cells on resulting metabolite concentrations. Through a determination of system constants and numerical solution to the equations, experimental batch and continuous culture results for cell concentration transients could be simulated by the model. The results indicated that despite selective pressure, plasmid-free cell growth was significant.     

Mathematical analysis of two-phase mass transfer in a batch reactor for the chemical transformation of a steroid

A reactor is described for the conversion of the slightly water-soluble steroid testosterone (T) to 4-androstene-3, 17-dione (4-AD) by enzyme in the presence of excess cofactor. Since the enzyme is subject to substrate inhibition, reaction rates are strong functions of aqueous substrate concentration. High concentrations of the substrate, testosterone, per unit reactor volume are maintained within poly(dimethylsiloxane) beads that are suspended in the aqueous enzyme solution. Mass transfer (controlled by bead size, polymer to water volume ratio, enzyme loading) is used to control the degree and rate of conversion. The reactor dynamics are predicted over a wide range of reaction conditions. The product steroid is recovered in the polymeric beads from the enzyme solution.     

Tip size of ion-exchanger based K+-selective microelectrodes. I. Effects on selectivity

Double-barreled ion-exchanger based K+-selective microelectrodes (K+ ISMs) of a variety of tip diameters were used to study the dependency of ion selectivity upon tip size. The selectivity of K+ ISMs depended on tip size and barrel configuration. Within the range of tip diameters tested (approximately 0.5-6 micron) all K+ ISMs constructed of two barrels glued side by side ("figure-eight glass") exhibited sensitivity to K+ and NH4+. Figure-eight K+ ISMs with tip diameters less than 1.5 micron were not sensitive to tetramethylammonium, tetraethylammonium, or choline, whereas K+ ISMs with tip diameters greater than or equal to 1.5 micron sensed all of the quaternary amines. Tip size dependent selectivity was not present in K+ ISMs made from thick septum theta glass. The explanation for tip size dependent changes in ion selectivity is unknown but a discussion of theoretical possibilities is given.     

Ethanol vapours above lacrimal fluid in the rabbit

Ethanol was administered intravenously to rabbits. The concentration of ethanol, determined by gas chromatographic analysis, in lacrimal fluid was shown to reflect the concentration in plasma. The vapour above lacrimal fluid was analyzed in situ by the use of a small resistivity sensor that measures ethanol vapours. After a dose of approximately 750 mg/kg, the metabolic rates of ethanol determined by gas chromatographic analysis of plasma (226 +/- 13 mg.kg-1.h-1) and by eye ethanol vapour analysis (210 +/- 8 mg.kg-1.h-1) were virtually identical. The data suggest that ethanol eye vapour analysis may be an attractive, noninvasive method for the determination of ethanol in animals.     

Two-phase pulsatile flows through porous conical tubes of small diameters. Modelisation of the blood microcirculation

A theoretical study concerning two-component fluid pulsating flow through porous conical ducts is presented. The model corresponds to blood flows through small diameter porous conical vessels. This approach is based on a finite difference method. The physical hypothesis used were based on findings from simultaneous visualization methods. The influence of geometrical, hydrodynamical and structural parameters is systematically examined and related to velocity profiles, hydrostatic pressure.     

Synthesis of 5'-O-beta-D-glucopyranosyl and 5'-O-beta-D-galactopyranosyl derivatives of ribavirin

The synthesis of 5'-O-beta-D-glucopyranosyl and 5'-O-beta-D-galactopyranosyl derivatives (13 and 15, respectively) of the antiviral agent ribavirin are described. Direct glycosylation of 2',3'-O-isopropylideneribavirin with either tetra-O-acetyl-alpha-D-glucopyranosyl bromide (4) or tetra-O-acetyl-alpha-D-galactopyranosyl bromide (8) under Koenigs-Knorr conditions (i.e., silver carbonate, silver perchlorate, and Drierite in dichloromethane) followed by O-deacetylation of the reaction product gave the corresponding ortho esters. However, treatment of 2',3'-di-O-acetyl-5'-O-tritylribavirin (11) with 4 under the Bredereck modification of the Koenigs-Knorr reaction (i.e., silver perchlorate and Drierite in nitromethane) and subsequent deacetylation furnished the desired 1-(5-O-beta-D-glucopyranosyl-beta-D-ribofuranosyl)-1,2,4-triazole-3-carb oxamide (13). Similarly, reaction of 11 with 8 in the presence of AgClO4, and deprotection of the condensation product, gave 5'-O-beta-D-galactopyranosylribavirin (15). The beta-anomeric configuration of the D-glucosyl and D-galactosyl groups of 13 and 15 was assigned by 1H-n.m.r. studies.