HIV protease inhibitory bis-benzamide cyclic ureas: a quantitative structure-activity relationship analysis

A series of N,N'-disubstituted cyclic urea 3-benzamides has been synthesized and evaluated for HIV protease inhibition and antiviral activity. Some of these benzamides have been shown to be potent inhibitors of HIV protease with Ki < 0.050 nM and IC90 < 20 nM for viral replication and, as such, may be useful in the treatment of AIDS. The synthesis and quantitative structure-activity relationship for this benzamide series will be discussed.     

FDTD analysis of probe-fed cylindrical dielectric resonator antennaoperating in fundamental broadside mode

An analysis of a cylindrical dielectric resonator antenna operating at the fundamental broadside mode using the finite-difference time-domain (FDTD) method is presented. Good agreement between theoretical and experimental results on the input impedance of the DR antenna is obtained. The effects of the probe length, feed position and the dielectric constant on the input impedance are presented     

Cardiovascular responses to intracerebroventricular injection of GABA in renovascular hypertensive rats

Effects of central GABAergic stimulation on cardiovascular function were evaluated in 2-kidney, 1-clip (2K1C) renovascular hypertensive rats (RVHR). Intracerebroventricular injection (icv) of GABA (100 and 200 micrograms) reduced blood pressure (BP) to a greater degree in RVHR as compared with sham-operated controls, and the greatest response was seen in RVHR 4 wk after operation (4 wk-RVHR). In addition, a decreased sensitivity of baroreflex was observed in 4 wk-RVHR, and was improved by icv GABA. Pretreatment with icv captopril (200 micrograms) only reduced BP moderately in 4 wk-RVHR, but attenuated remarkably the depressor effect of GABA. On the contrary, pretreatment with ip captopril was less effective in attenuating the depressor effect of GABA. Our results indicated that RVHR was deficient in central GABAergic inhibition on BP control, for GABAergic stimulation reduced BP to a greater degree and improves the decreased sensitivity of baroreflex in RVHR; the depressor effect of GABA is mediated, at least in part, by inhibiting brain angiotensin system.     

Photoreflectance study of GaAs and GaAs/GaAlAs single quantum wells grown on (001) Si substrates

The optical features associated with biaxially strained bulk GaAs and three GaAs/GaAlAs quantum wells (QWs), with widths of 52 Å, 120 Å and 200 Å, grown on (001) Si have been studied using photoreflectance at 300 K and 77 K. The ordering and/or separation of the light- and heavy-hole quantum transitions in the QWs can be tuned by altering the width of the well.     

Immunohistochemistry of matrix metalloproteinases (MMP), their substrates, and their inhibitors (TIMP) during trophoblast invasion in the human placenta

The invasion of extravillous trophoblast cells into the maternal endometrium is one of the key events in human placentation. The ability of these cells to infiltrate the uterine wall and to anchor the placenta to it as well as their ability to infiltrate and to adjust utero-placental vessels to pregnancy depends, among other things, on their ability to secrete enzymes that degrade the extracellular matrix. Most of the latter enzymes belong to the family of matrix metalloproteinases. Their activity is regulated by the tissue inhibitors of matrix metalloproteinases. We have studied the distribution patterns of matrix metalloproteinases-1, -2, -3, and -9 and their inhibitors TIMP-1 and TIMP-2 as compared to the distribution of their substrates along the invasive pathway of extravillous trophoblast of 1st, 2nd, and 3rd trimester placentas by means of light microscopy on paraffin and cryostat sections as well as at the ultrastructural level (only 3rd trimester placenta). The comparison of different methods proved to be necessary, since the immunohistochemical distribution patterns of these soluble enzymes are considerably influenced by the pretreatment of tissues. All three methods revealed immunoreactivities of both, proteinases and their inhibitors, not only intracellularly in the extravillous trophoblast but also extracellularly in its surrounding matrix, the distribution patterns depending on the stage of pregnancy and on the degree of differentiation of trophoblast cells along their invasive pathway. Within the extracellular matrix, immunolocalization of matrix metalloproteinases as well as their inhibitors showed a specific relation to certain extracellular matrix molecules.     

Effect of the vascular endothelium on norepinephrine-induced contractions in uterine radial arteries from the nonpregnant and pregnant human uterus

OBJECTIVE: Our purpose was to investigate the role of the endothelium in the human uterine arterial response to norepinephrine in the nonpregnant and pregnant states. STUDY DESIGN: Tissue was obtained from six pregnant and six nonpregnant women undergoing cesarean section or hysterectomy. Uterine radial arteries were isolated and subjected to norepinephrine dose-response curves with and without intact endothelium. RESULTS: Responses were obtained over a dose range of 10(-8) to 10(-4) norepinephrine. Initially there was no difference between vessels from pregnant and nonpregnant patients, but removal of the endothelium significantly increased the response in vessels from pregnant women. Addition of nitro-L-arginine methyl ester when the endothelium was intact did not alter the dose-response curves. CONCLUSIONS: In pregnancy human uterine radial arteries are more sensitive to norepinephrine than during the nonpregnant state. This increase is countered by an endothelium-derived relaxing factor. The factor is unlikely to be nitric oxide.     

Physiological and biochemical characteristics of the ethyl tiglate production pathway in the yeast Saprochaete suaveolens

A yeast identified as Saprochaete suaveolens was investigated for its capacity to produce a large panel of flavouring molecules. With a production of 32 compounds including 28 esters, S. suaveolens seems to be a good producer of fruity flavours and fragrances and especially of unsaturated esters, such as ethyl tiglate. Physiological and biochemical analyses were performed in this study in an attempt to comprehend the metabolic route to the formation of this compound. We show that the accumulation of ethyl tiglate by S. suaveolens is specifically induced by isoleucine. However, and contrary to S. cerevisiae, which harbours a classical Ehrlich pathway leading to the production of 2‐methylbutanol from isoleucine, our results provide phenotypic and enzymological evidence of ethyl tiglate biosynthesis in S. suaveolens through the catabolism of this amino acid by the β‐oxidation pathway, which generates tiglyl‐CoA as a probable intermediate. A kinetic analysis of this flavour molecule during growth of S. suaveolens on glucose and isoleucine showed a phase of production of ethyl tiglate that culminated concurrently with isoleucine exhaustion, followed by a disappearance of this compound, likely due to reassimilation by the yeast. Copyright © 2014 John Wiley & Sons, Ltd.     

Preparation, isolation, analysis, and characterization of 3-benzo[a]pyrenyl-beta-D-glucopyranosiduronic acid: a metabolite of 3-hydroxybenzo[a]pyrene with potentially high carcinogenic activity

The aglycone, 3-hydroxybenzo[a]pyrene, was metabolized to 3-benzo[a]pyrenyl-beta-D-glucopyranosiduronic acid in the presence of uridine 5'-diphosphoglucuronic acid and rabbit liver microsomes. The course of the biosynthetic reaction was followed by fluorimetry and reverse-phase, paired-ion high pressure liquid chromatography (HPLC). Also, the HPLC system was used to analyze for glucuronide and 3-hydroxybenzo[a]pyrene during the isolation procedure. The existence of a glucuronide of 3-hydroxybenzo[a]pyrene was determined by radiotracer and enzymic techniques, utilizing the HPLC system. Field desorption and direct inlet mass spectral techniques were used to characterize the 3-hydroxybenzo[a]pyrene glucuronide.