PubMed · 6637009
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K H Kimbel. 1983-09-10. [Do we need combination preparations?].. https://pubmed.ncbi.nlm.nih.gov/6637009/
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New information on the high resolution structure of the membrane proton pump, transhydrogenase, now provides a framework for understanding kinetic descriptions of the enzyme. Here, we have studied redox reactions catalyzed by mixtures of the recombinant NAD(H)-binding component (dI) of Rhodospirillum rubrum transhydrogenase, and the recombinant NADP(H)-binding component (dIII) of either the R. rubrum enzyme or the human enzyme. By recording changes in the fluorescence emission of native and engineered Trp residues, the rates of the redox reaction with physiological nucleotides have been measured under stopped-flow conditions, for the first time. Rate constants for the binding reaction between NAD(+)/NADH and the R. rubrum dI.dIII complex are much greater than those between nucleotide and isolated dI. For the redox step between the physiological nucleotides on the R. rubrum dI. dIII complex, the rate constant in the forward direction, k(f) approximately 2900 s(-1), and that for the reverse reaction, k(r) approximately 110 s(-1). Comparisons with reactions involving an analogue of NAD(H) indicate that the rate constants at this step are strongly affected by the redox driving force.
Small angle X-ray scattering (SAXS) and photon correlation spectroscopy (PCS) are two methods to measure particle sizes in the order of 10 nm magnitude, which can be used to characterize reversed micellar systems, in this case reverse micelles consisting of lecithin and isopropyl myristate (IPM). In this study these micelles are loaded with different concentrations of the amphiphilic anti-glaucoma drug timolol maleate (TM). The PCS results are consistent with those yielded by SAXS, showing a decrease of particle size with higher TM concentration. In addition, SAXS is capable to give information about the particle shape. This kind of evaluation yields an ellipsoidal shape for micelles with low drug loads, which transform into nearly spherical micelles at higher drug concentrations.
The hypothalamic gonadotrophin-releasing hormone (GnRH) stimulates synthesis and secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH) by the gonadotrophic cells of the pituitary. The mechanisms of action of GnRH antagonists and of agonists is completely different. Due tot competitive blockage of GnRH receptors by antagonist administration, LH (and to a lesser extent FSH) levels drop rapidly. Moreover pituitary function normalizes immediately following cessation of medication. The direct and rapid action of GnRH antagonists, the dose dependent suppression of LH and FSH and the rapid restoration of hypophyseal function after cessation of the use of antagonists may shorten and simplify in-vitro fertilization, with less chance of side effects or complications. Further studies are required to decide whether antagonists can usefully be applied for other gynecological indications such as the polycystic ovary syndrome. The possibilities of profitable long term treatment will increase considerably if it proves possible to develop a sustained action formulation.