Soy supplementation and role of equol production capability in postmenopausal women using tibolone: effects on cardiovascular risk markers

Tibolone, a synthetic steroid, is effective in the treatment of postmenopausal symptoms. Its cardiovascular safety profile has been questioned, because tibolone reduces the levels of high-density lipoprotein (HDL) cholesterol. Soy-derived isoflavones may offer health benefits, particularly as regards lipids and also other cardiovascular disease (CVD) risk factors. The soy-isoflavone metabolite equol is thought to be the key as regards soy-related beneficial effects. We studied the effects of soy supplementation on various CVD risk factors in postmenopausal monkeys and postmenopausal women using tibolone. In addition, the impact of equol production capability was studied. A total of 18 monkeys received casein/lactalbumin (C/L) (placebo), tibolone, soy (a woman s equivalent dose of 138 mg of isoflavones), or soy with tibolone in a randomized order for 14 weeks periods, and there was a 4-week washout (C/L) in between treatments. Postmenopausal women using tibolone (N=110) were screened by means of a one-week soy challenge to find 20 women with equol production capability (4-fold elevation from baseline equol level) and 20 control women, and treated in a randomized cross-over trial with a soy powder (52 g of soy protein containing 112 mg of isoflavones) or placebo for 8 weeks. Before and after the treatments lipids and lipoproteins were assessed in both monkeys and women. In addition, blood pressure, arterial stiffness, endothelial function, sex steroids, sex hormone-binding globulin (SHBG), and vascular inflammation markers were assessed. A 14% increase in plasma low-density lipoprotein (LDL) + very low-density lipoprotein (VLDL) cholesterol was observed in tibolone-treated monkeys vs. placebo. Soy treatment resulted in a 18% decrease in LDL+VLDL cholesterol, and concomitant supplementation with tibolone did not negate the LDL+VLDL cholesterol-lowering effect of soy. A 30% increase in HDL cholesterol was observed in monkeys fed with soy, whereas HDL cholesterol levels were reduced (48%) after tibolone. Interestingly, Soy+Tibolone diet conserved HDL cholesterol levels. Tibolone alone increased the total cholesterol (TC):HDL cholesterol ratio, whereas it was reduced by Soy or Soy+Tibolone. In postmenopausal women using tibolone, reductions in the levels of total cholesterol and LDL cholesterol were seen after soy supplementation compared with placebo, but there was no effect on HDL cholesterol, blood pressure, arterial stiffness or endothelial function. Soy supplementation decreased the levels of estrone in equol producers, and those of testosterone in the entire study population. No changes were seen in the levels of androstenedione, dehydroepiandrosterone sulfate, or SHBG. The levels of vascular cell adhesion molecule-1 increased, and platelet-selectin decreased after soy treatment, whereas C-reactive protein and intercellular adhesion molecule-1 remained unchanged. At baseline and unrelated to soy treatment, equol producers had lower systolic, diastolic and mean arterial pressures, less arterial stiffness and better endothelial function than non-producers. To conclude, soy supplementation reversed the tibolone-induced fall in HDL cholesterol in postmenopausal monkeys, but this effect was not seen in women taking tibolone. Equol production capability was associated with beneficial cardiovascular changes and thus, this characteristic may offer cardiovascular benefits, at least in women using tibolone.

Thermal behaviours of sulphur-selenium mixtures

The thermal behaviours of sulphur, selenium and their mixtures have been studied over the range 40–450Dagger. It has been shown that the polymerization threshold temperature of sulphur,T Ø, decreases with increasing selenium content and follows the equilibrium copolymerization model proposed by Tobolsky and Owen. The formation of octa-atomic species Se8–xSx, where 8 >x > 4, takes place only after sulphur is in the liquid state. The rate of polymerization is enhanced by the addition of increasing amounts of selenium and this is reflected in the higher polymerization peak temperatures. The X-ray powder diffractograms show that all the sulphur-selenium melts belong to the same phase as that of SeS, though the constituent atoms are randomly distributed.

Vibrational analysis of 1,3-thiazolidine-2-thione and its selenium analogue

The i.r. spectra of 1,3-thiazolidine-2-thione, ?2-selone and their N-deuteriated derivatives have been investigated in the region between 4000 and 20 cm?1. A complete assignment of the fundamental vibrational frequencies has been made based upon the normal coordinate analysis carried out using a simple Urey�Bradley force field supplemented by the valence force constants for the out-of-plane vibrations of the planar molecular skeleton. The proposed assignments are discussed in relation to the group frequencies in structurally related molecules and in terms of the computed potential energy distributions among the symmetry coordinates.

Chronic suppression of testicular function by constant infusion of gonadotropin-releasing hormone agonist and testosterone supplementation in the bonnet monkey (Macaca radiata)

Objective: To study the efficacy of long-term buserelin acetate infusion to desensitize pituitary and block testicular function in adult male monkeys (Macaca radiata). Animals: Proven fertile male monkeys exhibiting normal testicular function. Protocol: Each of the control (n = 5) and experimental monkeys (n = 10) received a fresh miniosmotic pump every 21 days, whereas pumps in controls delivered vehicle of experimentals released 50-mu-g buserelin acetate every 24 hours. On day 170 (renewed every 60 days) a silastic capsule containing crystalline testosterone (T) was implanted in the experimental monkeys. At the end of 3 years, treatment was stopped, and recovery of testicular function and fertility monitored. Results: (1) Treatment resulted in marked reduction of nocturnal but not basal serum T; (2) the pituitary remained desensitized to buserelin acetate throughout the 3-year period; (3) animals were largely azoospermic with occasional oligospermia exhibited by two monkeys; and (4) withdrawal of treatment restored testicular function, with 70% of animals regaining fertility. Conclusion: Long-term infertility (but restorable) can be induced in male monkeys by constant infusion of buserelin acetate and T.

A Change in the 3(10)- to alpha-Helical Transition Point in the Heptapeptides Containing Sulfur and Selenium

Crystal structures of three heptapeptides Boc-Ala-Leu-Aib-XXX-Ala-Leu-Aib-OMe (where XXX = methionine in peptide A, selenomethionine in peptide B, and S-benzyl cysteine in peptide C) reveal mixed 3(10)-/alpha-helical conformations with R factors of 6.94, 5.79, and 5.98, respectively. All the structures were solved in the P2(1)2(1)2(1) space group. 3(10)- to a-helical transitions are observed in all of these peptides. The helices begin as a 3(10)-helical segment at the N-terminus and then transit for peptides A and C at residue Aib(3) carbonyl (O(3)), while for peptide B the transition occurs at residue Leu(2) carbonyl oxygen (O(2)). There are water molecules associated in the crystal of each of these peptides and they form different types of hydrogen bonding patterns in each crystal. The observations suggest that 3(10)- to alpha-helical transition is sequence dependent in these short heptapeptide sequences.

Structural characterization of angiotensin I-converting enzyme in complex with a selenium analogue of captopril

Human somatic angiotensin I-converting enzyme (ACE), a zinc-dependent dipeptidyl carboxypeptidase, is central to the regulation of the renin-angiotensin aldosterone system. It is a well-known target for combating hypertension and related cardiovascular diseases. In a recent study by Bhuyan and Mugesh [Org. Biomol. Chem. (2011) 9, 1356-1365], it was shown that the selenium analogues of captopril (a well-known clinical inhibitor of ACE) not only inhibit ACE, but also protect against peroxynitrite-mediated nitration of peptides and proteins. Here, we report the crystal structures of human testis ACE (tACE) and a homologue of ACE, known as AnCE, from Drosophila melanogaster in complex with the most promising selenium analogue of captopril (SeCap) determined at 2.4 and 2.35 angstrom resolution, respectively. The inhibitor binds at the active site of tACE and AnCE in an analogous fashion to that observed for captopril and provide the first examples of a protein-selenolate interaction. These new structures of tACE-SeCap and AnCE-SeCap inhibitor complexes presented here provide important information for further exploration of zinc coordinating selenium-based ACE inhibitor pharmacophores with significant antioxidant activity.

Effect of selenium addition on the GeTe phase change memory alloys

Compositional dependent investigations of the bulk GeTe chalcogenides alloys added with different selenium concentrations are carried out by X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), electron probe micro-analyzer (EPMA) and differential scanning calorimetry (DSC). The measurements reveal that GeTe crystals are predominant in alloys up to 0.20 at.% of Se content indicating interstitial occupancy of Se in the Ge vacancies. Raman modes in the GeTe alloys changes to GeSe modes with the addition of Se. Amorphousness in the alloy increases with increase of Se and 0.50 at.% Se alloy forms a homogeneous amorphous phase with a mixture of Ge-Se and Te-Se bonds. Structural changes are explained with the help of bond theory of solids. Crystallization temperature is found to be increasing with increase of Se, which will enable the amorphous stability. For the optimum 0.50 at.% Se alloy, the melting temperature has reduced which will reduce the RESET current requirement for the phase change memory applications. (C) 2012 Elsevier B.V. All rights reserved.

Tetraethylammonium Tetraselenotungstate: A Versatile Selenium Transfer Reagent in Organic Synthesis

Organoselenium compounds have attracted intense research owing to their unique biological properties as well as pharmaceutical significance. Progress has been made in developing reagents for incorporation of selenium in an efficient and controlled manner. Herein, we present a review on the recently developed selenium reagent, tetraethylammonium tetraselenotungstate, Et4N](2)WSe4 as a versatile selenium transfer reagent in organic synthesis. Tetraselenotungstate has been successfully used for the synthesis of a number of functionalized diselenides, sugar- and nucleoside-derived diselenides, seleno-cystines, selenohomocystines, selenoamides, selenoureas and sugar- and nucleoside-based cyclic-selenide derivatives. Additionally, this reagent has been employed for the ring opening of aziridines to synthesize a variety of beta-aminodiselenides. A new selena-aza-Payne type rearrangement of aziridinemethanoltosylates mediated by tetraselenotungstate for the synthesis of allyl amines is also discussed.

Selenium adsorption on Au(111) and Ag(111) surfaces: adsorbed selenium and selenide films

Results of a high resolution photoemission and electrochemistry study of Se adsorption Au(111) and Ag(111) surfaces performed by immersion of pristine samples into an aqeuous solution of Na2Se are presented. Cyclic voltammetry on Au shows formation of selenium adsorbed species and the structures observed in reductive desorption are to the atomic and polymeric species observed in XPS. In the case of Au(111) XPS spectra in the Se(3d) region indeed show two main features attributed to Se chemisorbed atomically and polymeric Se-8 features.' Smaller structures due to other types of Se conformations were also observed. The Au(4f) peak line, shape does not show core level, shifts: indicative of Au selenide formation the case of silver, XPS spectra for the Ag(3d) show a broadening of the peak and a deconvolution into Ag-B bulk like Ag-Se components shows that the Ag-Se is located at a lower binding energy, an effect similar to oxidation and sulfidation of Ag. The Se(3d) XPS spectrum is found to be substantially different from the Au case and dominated by atomic type Se due to the selenide, though a smaller intensity Se structure at an energy similar to the Se-8 structure for Au is also observed. Changes in the valence band region. related to Se adsorption are reported.

Selenium in Diketopyrrolopyrrole-based Polymers: Influence on Electronic Properties and Charge Carrier Mobilities

Diketopyrrolopyrrole (DPP)-based pi-conjugated copolymers with thiophene have exceptionally high electron mobilities. This paper investigates electronic properties and charge carrier mobilities of selenophene containing analogues. Two new copolymers, with alternating thiophene DPP (TDPP) and selenophene DPP (SeDPP) units, were synthesized. Two side-chains, hexyl (Hex) and triethylene glycol (TEG) were employed, yielding polymers designated as PTDPPSeDPP-Hex and PTDPPSeDPP-TEG. Selenophene systems have smaller band gaps, with concomitant enhancement of the stability of the reduced state. For both polymers, ambipolar mobilities were observed in organic field-effect transistors (OFET). Grazing incidence X-ray diffraction (GIXD) data indicates preferential edge-on orientation of PTDPPSeDPP-TEG, which leads to superior charge transport properties of the TEG substituted polymer, as compared to its Hex analogue. Time-dependent-density functional theory (TDDFT) calculations corroborate the decrease in the optical band gap with the inclusion of selenophene. Ambipolar charge transport is rationalized by exceptionally wide conduction bands. Delta SCF calculations confirm the larger electron affinity, and therefore the greater stability, of the reduced form of the selenophene-containing DPP polymer in presence of chloroform.

Elastic Properties Of Sulphur And Selenium Doped Ternary PbTe Alloys By First Principles

Lead telluride (PbTe) is an established thermoelectric material which can be alloyed with sulphur and selenium to further enhance the thermoelectric properties. Here, a first principles study of ternary alloys PbSxTe(1-x) and PbSexTe(1-x) (0 <= x <= 1) based on the Virtual Crystal Approximation (VCA) is presented for different ratios of the isoelectronic atoms in each series. Equilibrium lattice parameters and elastic constants have been calculated and compared with the reported data. Anisotropy parameter calculated from the stiffness constants showed a slight improvement in anisotropy of elastic properties of the alloys over undoped PbTe. Furthermore, the alloys satisfied the predicted stability criteria from the elastic constants, showing stable structures, which agreed with the previously reported experimental results.

Combined inhalation and oral supplementation of Vitamin A and Vitamin D: A possible prevention and therapy for tuberculosis

Tuberculosis is continuing as a problem of mankind. With evolution, MDR and XDR forms of tuberculosis have emerged from drug sensitive strain. MDR and XDR strains are resistant to most of the antibiotics, making the management more difficult. BCG vaccine is not providing complete protection against tuberculosis. Therefore new infections are spreading at a tremendous rate. At the present moment there is experimental evidence to believe that Vitamin A and Vitamin D has anti-mycobacterial property. It is in this context, we have hypothesized a host based approach using the above vitamins that can cause possible prevention and cure of tuberculosis with minimal chance of resistance or toxicity. (C) 2015 Elsevier Ltd. All rights reserved.