Steady-state kinetic studies with the polysulfonate U-9843, an HIV reverse transcriptase inhibitor

The tetramer of ethylenesulfonic acid (U-9843) is a potent inhibitor of HIV-1 RT^* and possesses excellent antiviral activity at nontoxic doses in HIV-1 infected lymphocytes grown in tissue culture. Kinetic studies of the HIV-1 RT-catalyzed RNA-directed DNA polymerase activity were carried out in order to determine if the inhibitor interacts with the template: primer or the deoxyribonucleotide triphosphate (dNTP) binding sites of the polymerase. Michaelis-Menten kinetics, which are based on the establishment of a rapid equilibrium between the enzyme and its substrates, proved inadequate for the analysis of the experimental data. The data were thus analyzed using steady-state Briggs-Haldane kinetics assuming that the template:primer binds to the enzyme first, followed by the binding of the dNTP and that the polymerase is a processive enzyme. Based on these assumptions, a velocity equation was derived which allows the calculation of all the specific forward and backward rate constants for the reactions occurring between the enzyme, its substrates and the inhibitor. The calculated rate constants are in agreement with this model and the results indicated that U-9843 acts as a noncompetitive inhibitor with respect to both the template:primer and dNTP binding sites. Hence, U-9843 exhibits the same binding affinity for the free enzyme as for the enzyme-substrate complexes and must inhibit the RT polymerase by interacting with a site distinct from the substrate binding sites. Thus, U-9843 appears to impair an event occurring after the formation of the enzyme-substrate complexes, which involves either an event leading up to the formation of the phosphoester bond, the formation of the ester bond itself or translocation of the enzyme relative to its template:primer following the formation of the ester bond.     

Nucleolus organizer region location and ‘ring’ chromosomes in the bharal

Summary Silver-staining has been used to identify the nucleolus organizer regions (NORs) in the bharal. These show homology with sheep, goat, cattle and aoudad. The association of the NORs on both telomeres of chromosome 3 results in a ring chromosome.     

Hemolymph volume determination in the tomato fruitworm,Heliothis zea

Summary The hemolymph volume ofHeliothis zea larvae was determined by the amaranth dye method and found to vary from 28 to 288 l. It averaged 30.6% of b.wt, a value comparable to that obtained with C¹⁴ inulin. Amaranth became evenly distributed in the hemocoele in 3–5 min.     

Neuroleptic-induced prolactin rise: Influence of pharmacological alterations of different neurotransmitter systems

Summary Oral administration of 2 neuroleptic drugs, haloperidol and LR511 induced in male rats a marked, dose-dependent and sustained rise of plasma prolactin.     

A study on the effects of some drugs on DOCA induced hypertension in the rat

Chronic treatment with various drugs reduced the increase in arterial blood pressure, the ventricular hypertrophy and the thickening of pulmonary arterial and arteriolar walls.     

Effect of ethidium bromide onDrosophila melanogaster andDrosophila simulans

Summary Ethidium bromide was fed toD. melanogaster andD. simulans males in order to test its toxic capacity and potency for the induction of dominant lethals. Our results show that ethidium bromide has a high toxicity and likewise produces dominant lethals to a significant extent in both species, but more effectively inD. melanogaster.     

Starfish saponins. Part 101. Further 24-O-glycosidated steroids from the starfishHacelia attenuata

Summary On the basis of comparative spectral data, the structures of 3 novel steroidal glycosides from the Mediterranean starfishHacelia attenuata have been elucidated as3, 4 and5. These are further examples of a novel group of 24-O-glycosidated steroids recently encountered in the same species and in the Pacific speciesProtoreaster nodosus.Part 9. L. Minale, C. Pizza, R. Riccio and F. Zollo, Experientia39 (1983) 567. This contribution is part of the Progetto Finalizzato Chimica fine e secondaria del C.N.R., Roma.Acknowledgments. We thank Prof. K. Nakanishi, Columbia University, New York, for FD-mass spectral analyses, the Centro Interfacoltà di Metodologie Chimico-Fisiche for 270 MHz NMR facilities, and Miss R. Aquino for part of the experimental work.     

Is prostacyclin subserving a vasodilator effect of methoxamine involving alpha adrenoreceptors?

The influence of methoxamine on the contractile tension of isolated rat abdominal aorta, and on its capacity to produce a platelet antiaggregating substance, were explored. Methoxamine stimulated platelet antiaggregation and diminished arterial tone. The last action was blocked by phentolamine as well as by inhibitors of cyclo-oxygenase and prostacyclinsynthetase.