Correction: A hexagonal Ni6 cluster protected by 2-phenylethanethiol for catalytic conversion of toluene to benzaldehyde.

Correction for 'A hexagonal Ni6 cluster protected by 2-phenylethanethiol for catalytic conversion of toluene to benzaldehyde' by Anthony M. S. Pembere et al., Phys. Chem. Chem. Phys., 2019, 21, 17933-17938.

A hexagonal Ni6 cluster protected by 2-phenylethanethiol for catalytic conversion of toluene to benzaldehyde.

We have synthesized single crystals of a 2-phenylethanethiol-protected Ni6 nanocluster, namely Ni6(C8H9S)12, which shows a hexagonal metallic core structure and reasonable stability. Interestingly this cluster is found to be an excellent candidate for the catalytic oxidation of toluene to benzaldehyde, with 100% conversion and 91% selectivity, showing application potential as an aromatic aldehyde in industry. Using DFT calculations, we rationalize the catalytic reaction mechanism for the conversion of toluene to benzaldehyde, and demonstrate that the presence of H2O2 initiates the Ni6 cluster via a highly exothermic step to form a Ni6O* intermediate which then results in active sites for the oxidation of toluene. What is interesting is that the likely steric geometry matching of the six-ring Ni6 core, a dozen phenylethanethiol ligands and the aromatic reactant toluene could attain a synergistic effect to facilitate the production of benzaldehyde free of catalyst support.

How Partial Atomic Charges and Bonding Orbitals Affect the Reactivity of Aluminum Clusters with Water?

We present here a further insight on the hydrogen evolution reactions (HER) of aluminum clusters with one and multiple water molecules. Along with natural bond orbital (NBO) and frontier molecular orbital (FMO) analysis, we compared the reactivities of both anionic and neutral Al13, Al12, Al7, and Al6 clusters with water in gas phase. It is found that electron flow interactions between these typical Al clusters and H2O initiate their reactions, allowing varied charge distribution on the cluster. With an emphasis on the typical Al6 cluster, we checked out the reactive intermediates, activated complexes, transition states, bond breaking and stereochemistry for it to react with two and four water molecules, respectively. The kinetic- and thermodynamic- allowed reaction pathways are coincident with the experimental observation of Al n(OH)4- being dominant products for Al n- clusters reacting with water. It is illustrated how additional water molecules function as catalysts enabling strengthened HER activity.

Cohort study of malignancies and hospitalized infectious events in treated and untreated patients with psoriasis and a general population in the United States.

BACKGROUND: Psoriasis is associated with risk of malignancy. Some psoriasis treatments may increase the risk of hospitalized infectious events (HIEs). OBJECTIVES: To evaluate rates of malignancies and HIEs in patients with psoriasis. METHODS: This retrospective cohort study utilized data from MarketScan(®) databases. Cohorts included adult general population (GP), patients with psoriasis, and patients with psoriasis treated with nonbiologics, adalimumab, etanercept, infliximab or phototherapy. Outcomes included incidence rates (IRs) per 10 000 person-years observation (PYO) for all malignancies excluding nonmelanoma skin cancer (NMSC), lymphoma, NMSC, and per 10 000 person-years of exposure (PYE) for HIEs. RESULTS: Incidence rates [95% confidence interval (CI)] for all malignancies except NMSC were 129 (127-130) and 142 (135-149) for GP (PYO = 51 071 587) and psoriasis (PYO = 119 432) cohorts, respectively; 10·9 (10·5-11·3) and 12·9 (10·9-14·8) for lymphoma; and 145 (144-147) and 180 (173-188) for NMSC. Rates for all malignancies excluding NMSC were similar among treatments but variable for lymphoma and NMSC. IRs (95% CI) for HIEs were 332 (256-408) for the nonbiologic cohort (PYE = 3528); 288 (206-370) for etanercept (PYE = 6563); 325 (196-455) for adalimumab (PYE = 2772); 521 (278-765) for infliximab (PYE = 1058); and 334 (242-427) for phototherapy (PYE = 1797). IRs for HIEs were lowest for etanercept and higher in patients on baseline systemic corticosteroids across treatment cohorts. CONCLUSIONS: Malignancy rates were higher in patients with psoriasis than the GP, but these treatments did not appear to increase malignancy risk.

Incidence rates of malignancies and hospitalized infectious events in patients with psoriasis with or without treatment and a general population in the U.S.A.: 2005-09.

BACKGROUND: Rates of malignancies and hospitalized infectious events (HIEs) among psoriasis patients are higher than in the general population, but it is unclear if higher rates are associated with the underlying inflammatory state, treatments or both. OBJECTIVES: To assess the incidence of malignancies and HIEs in a healthy US population, a psoriasis population, and four treated psoriasis populations. METHODS: Using a US claims database, we identified a general population, a psoriasis cohort, and four treatment cohorts [non-biologic systemics, etanercept, other TNF blockers (adalimumab, infliximab) and phototherapy] to assess the incidence of lymphomas, nonmelanoma skin cancer (NMSC), all malignancies (excluding NMSC), and HIEs, standardized for age and sex. RESULTS: Among 40 987 patients with psoriasis, 11% were prescribed non-biologics, 15% etanercept, 6% other TNF blockers and 11% phototherapy. For all cancers, the psoriasis population rate (114/10 000 person-years) was 20% greater than the rate found in the general population (95/10 000 person-years). For NMSC, the psoriasis population rate (129/10 000 person-years) was 65% greater than the general population rate (78/10 000 person-years). The incidence rate for each treatment modality was lower than the overall psoriasis cohort, except for phototherapy. There was little difference in the rates of lymphomas. NMSC rates were higher among patients treated with phototherapy. HIE rates ranged from 165/10 000 person-years for the phototherapy group to 262/10 000 person-years for the other anti-TNF group. CONCLUSIONS: Patients with psoriasis appear to have higher rates of malignancy and HIE than the general population, with little difference in rates between the treatment methods, except for a higher rate of cancer among those receiving phototherapy.

Cobalt group transition metals (TM: Co, Rh, Ir) coordination of S-doped porphyrins (TM_S@PPR) as sensors for molecular SO2 gas adsorption: a DFT and QTAIM study.

CONTEXT: The intricate challenges posed by SO2 gas underscore the imperative for meticulous monitoring and detection due to its adverse effects on health, the environment, and equipment integrity. Hence, this research endeavors to delve deeply into the intricate realm of transition-metals functionalized sulfur-doped porphyrins (S@PPR) surfaces through a comprehensive computational study. The electronic properties revealed that upon adsorption, Ir_S@PPR surface reflects the least energy gap of 0.109 eV at the O-site of adsorptions, indicating an increase in electrical conductivity which is a better adsorption trait. Owing to the negative adsorption energy observed, the adsorption behavior is described as chemisorption, with the greatest adsorption energy of - 10.306 eV for Ir_S@PPR surface at the S-site of adsorption. Based on the mechanistic attributes, iridium-functionalized S@PPR surface is a promising detecting material towards the sensing of SO2 gas. This report will provide useful insight for experimental researchers in selecting and engineering materials to be used as detectors for SO2 gas pollutant. METHOD: All theoretical investigations were carried out using density functional theory (DFT), calculated at PW6B95-D3/GenECP/Def2svp/LanL2DZ computational method.

A data-guided approach for the evaluation of zeolites for hydrogen storage with the aid of molecular simulations.

CONTEXT: This study employs a data-guided approach to evaluate zeolites for hydrogen storage, utilizing molecular simulations. The development of efficient and practical hydrogen storage materials is crucial for advancing clean energy technologies. Zeolites have shown promise as potential candidates due to their unique porous structure and tunable properties. However, the selection and design of suitable zeolites for hydrogen storage remain challenging. Therefore, this work aims to address this materials science question by utilizing molecular simulations and data-guided approaches to evaluate zeolites' performance for hydrogen storage. The results obtained from this study provide valuable insights into the evaluation of zeolites for hydrogen storage. Through molecular simulations, we analyze the adsorption behavior of hydrogen molecules in various zeolite structures. The performance of different zeolite frameworks in terms of hydrogen storage capacity, adsorption energy, and diffusion properties is assessed. Linde type A zeolite (LTA) had the highest capacity with a hydrogen capacity of 4.8wt% out of the 233 investigated zeolites. Furthermore, we investigate the influence of different factors such as mass (M), density (D), helium void fraction (HVF), accessible pore volume (APV), gravimetric surface area (GSA), and largest overall cavity diameter (Di) on the hydrogen storage performance of zeolites. The results show that Di, D, and M have a negative effect on the percentage weight capacity, while GSA and VSA have the highest positive contribution to the percentage weight. This study, therefore, provides new insights into the factors that affect their hydrogen storage capacity by exhibiting the importance of considering multiple factors when evaluating the performance of zeolites and demonstrates the potential of combining different computational methods to provide a more comprehensive understanding of materials. The current study contributes to the understanding of zeolite-based materials for hydrogen storage applications, aiding in the development of more efficient and practical hydrogen storage systems. METHODS: Computational techniques were employed to investigate the hydrogen storage properties of zeolites. Molecular simulations were performed using classical force fields and molecular dynamics methods. The calculations were carried out at a force field level of theory with the GGA functional. To accurately capture the thermodynamics and kinetics of hydrogen adsorption, enhanced sampling techniques such as Monte Carlo simulations and molecular dynamics with metadynamics were utilized. We employed Grand Canonical Monte Carlo (GCMC) simulations to model hydrogen adsorption in zeolite structures for hydrogen storage. Our approach involved performing a substantial number of Monte Carlo steps (10,000) to ensure system equilibration and precise results. We defined a cutoff distance for particle interactions as 12.5 Ǻ and considered 0.000e framework charge per cell and 0.000e sorbate charge in energy calculations. The choice of an appropriate simulation cell size (50 × 50 × 50) Ǻ was crucial, mirroring real-world conditions. We specified lower and upper fugacity values (1 to 10 atm) to capture the range of gas pressures in the simulations. These methodical steps collectively enabled us to accurately model hydrogen adsorption within zeolites, forming the core of our hydrogen storage evaluation. In this research, we utilized DFT calculations to thoroughly investigate the interactions between zeolites and hydrogen. We employed pseudopotentials to describe electron behavior in zeolite systems, choosing them in line with DFT norms and basis set compatibility. Our simulation cell design replicated zeolite periodicity and eliminated boundary effects. Pre-geometry optimization was performed with HyperChem29, ensuring stable conformations with strict convergence criteria. We utilized 6-31 + G(d) and LanL2DZ basis sets for light and heavy atoms, aligning with field standards for computational efficiency and precision. A machine learning algorithm was used to rank the importance of various structural features such as mass (M), density (D), helium void fraction (HVF), accessible pore volume (APV), gravimetric surface area (GSA), and largest overall cavity diameter (Di) and how they affect the capacity of the zeolites. Machine learning analysis was performed with the Scikit-learn library, an open-source Python tool. We employed a range of machine learning models, including SVMs, random forests, and neural networks, primarily for data analysis and feature extraction. Pearson correlation analysis, a classical statistical technique, was used to evaluate linear relationships between variables and assess the strength and direction of these relationships. It served as a complementary tool to understand the interplay of variables in our dataset, distinguishing it from machine learning algorithms. Further quantum chemical calculations were also performed to calculate the adsorption energy, global reactivity electronic descriptors, and natural bond orbital analysis in order to provide insights into the interaction of the zeolites with hydrogen. The simulations and data analysis were performed using BIOVIA material studio software, Gaussian, and Origin Pro software.

Mechanism and dynamics of Baeyer-Villiger oxidation of furfural to maleic anhydride in presence of H2O2 and Au clusters.

CONTEXT: The increasing demand for fuels and chemicals in the world has prompted the exploration of various forms of renewable energy resources. Using C5-based furfural as the platform to replace the fossil energy resources is greatly attractive because of its abundance and environmental friendliness. Here we study the activity, selectivity, and possible reaction pathways for the Baeyer-Villiger oxidation of furfural over small Au clusters using hydrogen peroxide as oxidant. Furfural reacts with hydrogen peroxide in the presence of the catalysts with 93% selectivity towards maleic anhydride. Natural population analysis, frontier molecular orbital analysis, and spectroscopic analysis are used to illustrate the interaction mechanism between C5H4O2, H2O2, and Au. Reaction pathways leading to the formation of maleic anhydride are also explored. The reaction of C5H4O2 with H2O2 in the absence of a catalyst bears a relatively high transition state energy barrier of 2.98 eV for the first step involving absorption of H atom of H2O2 on the -OH group of C5H4O2. This is in agreement with the blank experiment where there were rare oxidation products observed in the absence of the metal cluster catalysts. On the other hand, transition state energies in the presence of the Au metal clusters are lower and the most feasible pathway is where the substrate and H2O2 co-bind on the Au catalyst and H2O2 molecule transfers an oxygen to the substrate, leading to the cleavage of the O-O bond. METHODS: DFT calculations were done with B3PW91 functional. 6-311G(df, p) basis set was used for C, O, and H and aug-cc-pVDZ-PP was used for gold atoms. Gaussian 09 software was used for the calculations. Multiwfn 3.7 dev was used for the quantum theory of atoms-in-molecules (QTAIM) investigations.

Molecular simulation of Cu, Ag, and Au-decorated Si-doped graphene quantum dots (Si@QD) nanostructured as sensors for SO2 trapping.

In view of the numerous environmental hazards and health challenges linked to sulfur (iv) oxide (SO2), an indirect greenhouse gas, and the resultant need to develop efficient gas nanosensor devices, this research had as its principal focus on the theoretical evaluation of the gas sensing potential of metals: Ag, Au and Cu functionalized silicon-doped quantum dots (Si@QD) for the detection and adsorption of SO2 gas investigated using the first-principles density functional theory (DFT) computation at the B3LYP-D3(BJ)/def2-SVP level of theory. Eight (8) possible adsorption modes: SO2_O_Si@QD, SO2_O_Ag_Si@QD, SO2_O_Au_Si@QD, SO2_O_Cu_Si@QD, SO2_S_Si@QD, SO2_S_Ag_Si@QD, SO2_S_Au_Si@QD, and SO2_S_Cu_Si@QD were considered based on SO2 interactions with the studied materials at the -S and -O sites of the SO2 molecule. The counterpoise correction (BSSE) showed that five of the eight interactions had favorable Ead + BSSE values ranging from -0.31 to -1.98 eV. All the eight interactions were observed to be thermodynamically favorable with ΔG and ΔH ranging from -129.01 to -200.24 kcal/mol and -158.26 to -229.73 kcal/mol respectively. Results from the topology analysis reveal that van der Waals forces occurred the greatest at the gas-sensor interphase while SO2_S_ Cu_Si@QD is predicted to have the highest sensing potency based on the conductivity and recovery time estimations. These results confirm the potential efficient feasibility of real-world device application of the metals (Ag, Au, Cu) functionalized Si-doped QDs.

Single-atoms (N, P, S) encapsulation of Ni-doped graphene/PEDOT hybrid materials as sensors for H2S gas applications: intuition from computational study.

This comprehensive study was dedicated to augmenting the sensing capabilities of Ni@GP_PEDOT@H2S through the strategic functionalization with nitrogen, phosphorus, and sulfur heteroatoms. Governed by density functional theory (DFT) computations at the gd3bj-B3LYP/def2svp level of theory, the investigation meticulously assessed the performance efficacy of electronically tailored nanocomposites in detecting H2S gas-a corrosive byproduct generated by sulfate reducing bacteria (SRB), bearing latent threats to infrastructure integrity especially in the oil and gas industry. Impressively, the analysed systems, comprising Ni@GP_PEDOT@H2S, N_Ni@GP_PEDOT@H2S, P_Ni@GP_PEDOT@H2S, and S_Ni@GP_PEDOT@H2S, unveiled both structural and electronic properties of noteworthy distinction, thereby substantiating their heightened reactivity. Results of adsorption studies revealed distinct adsorption energies (- 13.0887, - 10.1771, - 16.8166, and - 14.0955 eV) associated respectively with N_Ni@GP_PEDOT@H2S, P_Ni@GP_PEDOT@H2S, S_Ni@GP_PEDOT@H2S, and Ni@GP_PEDOT systems. These disparities vividly underscored the diverse strengths of the adsorbed H2S on the surfaces, significantly accentuating the robustness of S_Ni@GP_PEDOT@H2S as a premier adsorbent, fuelled by the notably strong sulfur-surface interactions. Fascinatingly, the sensor descriptor findings unveiled multifaceted facets pivotal for H2S detection. Ultimately, molecular dynamic simulations corroborated the cumulative findings, collectively underscoring the pivotal significance of this study in propelling the domain of H2S gas detection and sensor device innovation.

Synthesis, characterization, and theoretical studies of the photovoltaic properties of novel reactive azonitrobenzaldehyde derivatives.

All dyes conduct but at different degrees of absorption; it is interesting to study the degree of conductivity and absorptivity of novel reactive azo-dyes in respect to dye-sensitized solar cells (DSSCs) to ascertain their viability for such applications. In this study, four novel reactive azo-dyes were experimentally synthesized from p-aminobenzaldehyde, 4-amino-3-nitrobenzaldehyde, and aniline through series of condensation and coupling reactions. The various functional groups, molecular connectivities, and molecular weight of the various fragments of the synthesized dyes were elucidated using the GC-MS, FT-IR, UV-vis, and NMR respectively. The experimentally determined structures were modeled and investigated using density functional theory (DFT) and time-dependent density functional theory (TD-DFT) approaches to computationally compute the electronic structure properties, reactivity, absorption and solvatochromism in four different phases: gas, ethanol, acetone, and water, and the photovoltaic properties for possible applications in dye-sensitized solar cells (DSSCs). By comparing the HOMO (E H) and the LUMO (E L) energies from the results obtained demonstrates that dye D has the highest E L energy value of -2.48 eV with a relatively lowest E H energy value of -5.63 eV such that it lies underneath the conduction band edge of TiO2 which is necessary to enable charge regeneration. Pi-electron delocalization was observed from the natural bond orbital (NBO) calculations between the different aromatic rings with dye B and A having the relatively highest and least second-order stabilization energies between σ* → σ* and LP* → LP interacting orbitals respectively. It is also observed in all the solvents that the Gibbs free energy of injection (ΔG inject) is greater than 0.2 eV and hence, all the studied azo structures in the four phases provided efficient electron injection and light harvesting efficiency (LHE), however, the value of ΔG inject for dyes B and D is greatest in all the four phases and thus, provided the highest electron injection of all the dyes. From the fact-findings of quantum theory of atoms-in-molecules (QTAIM), dyes A and C have extra-stability due to their relatively high numbers of intramolecular H-bond interactions along with some additional intra-atomic bonding between atoms within the studied compounds. Hence, all the four dyes are good for DSSCs applications.

Persistence and switching patterns among women with varied osteoporosis medication histories: 12-month results from POSSIBLE US.

UNLABELLED: During the first year of Prospective Observational Scientific Study Investigating Bone Loss Experience (POSSIBE US), many women transitioned (i.e., discontinued or switched) from their baseline osteoporosis medication. Participants not on stable therapy at entry, with side effects, and with poor physical status were at higher risk of transitioning. Understanding factors associated with persistence may lead to improved outcomes. INTRODUCTION: Postmenopausal osteoporosis (PMO) medication use patterns may differ by treatment history and drug class. We describe these patterns among patients in primary care settings using patient-reported data. METHODS: Data from 3,006 participants of the POSSIBLE US were used to estimate the probability of a baseline PMO medication transition (i.e., discontinuation or switch) and hazard ratios (HRs) for predictors of these transitions. RESULTS: One year after study entry, the probability of persisting with a baseline medication was 66% (95% CI: 64-68%). After adjusting for age and osteoporosis diagnosis, factors at entry independently associated with a higher risk of baseline medication transition were treatment status cohort, side effect severity, and OPAQ-SV physical function score. Compared to participants stable on therapy at entry, others had a higher risk, ranging from HR = 1.59 (95% CI: 1.36-1.85) for those new to therapy to HR = 2.00 (95% CI: 1.27-3.15) for those who recently augmented therapy at entry. Participants reporting moderate (HR = 1.31, 95% CI: 1.09-1.57) or severe (HR = 1.88, 95% CI: 1.49-2.39) side effects had a higher risk than those not reporting side effects. Participants reporting Osteoporosis Assessment Questionnaire-Short Version physical function scores in the lowest tertile had a higher risk (HR = 1.27, 95% CI: 1.07-1.52) than those reporting scores in the highest tertile. CONCLUSION: Baseline osteoporosis medication transitions were common in the first year of POSSIBLE US. Participants not on stable therapy at entry, or who reported severe side effects, or had poor physical health status were at higher risk for these transitions.

Estrogenic soybean isoflavones and chronic disease Risks and benefits.

Many edible plants contain natural estrogens called phytoestrogens. These compounds possess mixed estrogen agonist-antagonist properties that are organ-specific in vivo. We have focused on estrogenic soybean isoflavones because of their potential extensive dietary availability. In this article, we review the clinical and experimental evidence for the possible benefits and risks of ingestion of estrogenic isoflavones throughout the life span, and highlight areas needing further elucidation.

Lack of effect of raloxifene on coronary artery atherosclerosis of postmenopausal monkeys.

Raloxifene has been shown to have estrogen agonist effects on bone and cholesterol metabolism while having estrogen antagonist effects on mammary gland and uterus. Reported here are the results of a study to determine whether raloxifene had the estrogen agonist effect of inhibiting coronary artery atherogenesis and to compare its effects with those of traditional conjugated equine estrogens (CEE) treatment. Ovariectomized (surgically postmenopausal) cynomolgus monkeys were fed a moderately atherogenic diet and treated with a placebo, raloxifene (1 mg/kg x day), raloxifene (5 mg/kg x day), or CEE (Premarin) at a dose that mimicked that of 0.625 mg/day in women. The effects of raloxifene on plasma lipid concentrations were generally comparable to those reported in postmenopausal women treated with raloxifene: reductions in low density lipoprotein cholesterol concentrations and no significant effects on high density lipoprotein cholesterol. We found no evidence that raloxifene had an estrogen agonist effect on coronary arteries. Treatment with CEE resulted in about a 70% reduction in coronary artery plaque size relative to that in the placebo group, whereas neither the low nor the high dose of raloxifene had an effect on coronary artery plaque size. The low dose raloxifene group had about 2 times more atherosclerosis and the high dose group had about 3 times more atherosclerosis than the CEE group.

Inhibition of postmenopausal atherosclerosis progression: a comparison of the effects of conjugated equine estrogens and soy phytoestrogens.

Experimental evidence was sought concerning whether soy phytoestrogens (SPEs) inhibit postmenopausal atherosclerosis progression/extent and, if so, their effectiveness relative to traditional estrogen replacement therapy. Premenopausal cynomolgus monkeys were fed a moderately atherogenic diet (26 months) to induce atherosclerosis. After ovariectomy, the moderately atherogenic diet was continued, and they were treated (36 months) with a control diet (soy protein depleted of SPEs), a diet containing SPEs in soy protein isolate, or a diet containing SPE-depleted soy protein with conjugated equine estrogens (CEE; Premarin) added. SPE effects on plasma lipids were better than those of CEE (higher high density lipoprotein cholesterol and no increase in triglyceride). Relative to the control group, CEE treatment inhibited (P = 0.0001), and SPE treatment partially inhibited (P = 0.10) the progression of atherosclerosis (common iliac artery atherosclerosis before and after treatment). CEE-treated monkeys had much less coronary artery atherosclerosis than the controls (P = 0.0002), whereas SPE-treated monkeys were intermediate in lesion extent between the controls and the CEE-treated animals (P = 0.02). Both CEE and SPE significantly reduced the extent of common carotid and internal carotid artery atherosclerosis, and the two treatment groups were not significantly different.

A comparison of tibolone and conjugated equine estrogens effects on coronary artery atherosclerosis and bone density of postmenopausal monkeys.

This study compared the effects of tibolone, a tissue-specific compound for the treatment of climacteric symptoms and the prevention of osteoporosis, with those of conjugated equine estrogens (CEE) with and without medroxyprogesterone (MPA) on bone mineral density and coronary atherosclerosis (CAA) of postmenopausal cynomolgus monkeys. The groups were tibolone [two doses were used, 0.05 mg/kg (LoTib) and 0.2 mg/kg (HiTib)], CEE (0.042 mg/kg), CEE (0.042 mg/kg) plus MPA (0.167 mg/kg given continuously), and a control group given no treatment for 2 yr. Compared with no treatment, bone mineral density was higher by 6.3% (P = 0.0004) in the LoTib group and by 9.5% (P = 0.02) in the HiTib group compared with 4.3% (P = 0.12) for CEE and 4.5% (P = 0.10) for CEE+MPA. Plasma high density lipoprotein cholesterol was reduced by 49% with HiTib and by 34% with LoTib. There were no differences in CAA between control and HiTib (P = 0.60) or LoTib (P = 0.58). CEE and CEE+MPA both reduced CAA by about 62% (CEE vs. control, P = 0.02; CEE+MPA vs. control, P = 0.01). Despite adverse effects of tibolone on plasma lipoprotein concentrations, there was no increase in CAA, suggesting that tibolone is a cardiovascular-safe treatment for climacteric symptoms and the prevention of osteoporosis.

Effects of soy isoflavones on atherosclerosis: potential mechanisms.

It has long been recognized that coronary heart disease rates are lower in Japan, where soy consumption is common, than in Western countries. In experimental studies, atherosclerosis was reduced in animals fed diets containing soy protein compared with those fed diets with animal protein. Recently, several lines of evidence have suggested that the components of soy protein that lower lipid concentrations are extractable by alcohol (eg, the isoflavones genistein and daidzein). We recently evaluated the relative effect of the soy protein versus the alcohol-extractable components of soy on cardiovascular disease and its risk factors. Young male and female cynomolgus monkeys were fed diets that contained either 1) casein-lactalbumin as the source of protein (casein), 2) soy protein isolate from which the isoflavones were alcohol extracted (SPI-), or 3) isoflavone-intact soy protein (SPI+). The SPI+ group had significant improvements in LDL cholesterol and HDL cholesterol. Only HDL cholesterol was significantly improved in the SPI- group males compared with the casein group. The casein group had the most atherosclerosis, the SPI+ group had the least, and the SPI- group was intermediate but did not differ significantly from the casein group. Potential mechanisms by which soy isoflavones might prevent atherosclerosis include a beneficial effect on plasma lipid concentrations, antioxidant effects, antiproliferative and antimigratory effects on smooth muscle cells, effects on thrombus formation, and maintenance of normal vascular reactivity.

Effect of atherogenic diet on lipoprotein lipase activity in cynomolgus monkeys.

Cynomolgus monkeys (Macaca fascicularis) fed monkey chow (n = 10) had a mean +/- SD post-heparin plasma lipoprotein lipase (LPL) activity level (14.7 +/- 5.5 units/ml) similar to that found in human beings (15.7 +/- 3.9 units/ml). However, the hepatic triglyceride lipase (H-TGL) in these monkeys was extremely low (0.5 +/- 0.3 units/ml) when compared with that in human beings (10.9 +/- 4.3 units/ml). The consumption of isocaloric atherogenic diets (0.2 mg cholesterol/Cal) with either saturated (P/S = 0.34) or polyunsaturated (P/S = 2.2) fat led to increased LPL activity levels (27.6 +/- 6.5 and 28.8 +/- 16.1 units/ml, respectively) and the accumulation of plasma low density lipoprotein cholesterol (LDL-C). The results indicate that cholesterol-containing atherogenic diets with either primarily saturated or polyunsaturated fat have similar potential for the increase of LPL activity. However, it is not clear whether the high dietary cholesterol content represents an obligatory component for the increase of LPL. We speculate that the high level of LPL in cynomolgus monkeys when fed a cholesterol-rich, high fat diet could be a contributing factor to the accumulation of excessive plasma LDL-C.

Effects of chronic hormone replacement on the renin-angiotensin system in cynomolgus monkeys.

OBJECTIVE: To characterize the effects of estrogen, estrogen combined with progestin, and no treatment in ovariectomized cynomolgus monkeys during long-term reproductive hormone replacement. METHODS: Forty-five surgically postmenopausal cynomolgus monkeys fed a lipid-lowering diet were administered a conjugated equine estrogen (Premarin, 7.2 micrograms/day for the first 8 months, then 166 micrograms/day for the remaining 22 months), alone or in combination with 650 micrograms/day medroxyprogesterone acetate (Cycrin) for 30 months, or left with no hormone replacement therapy. Animals were anesthetized with ketamine-pentobarbital, and samples were taken for measurements of plasma renin activity, angiotensin converting enzyme activity, and angiotensin peptides, angiotensin I (Ang I), angiotensin II (Ang II), and angiotensin-(1-7) [Ang-(1-7)]. RESULTS: Chronic replacement therapy with estrogen resulted in a significant elevation of the plasma renin activity [11.7 +/- 2.0 ng/ml per h control versus 22.8 +/- 4.6 ng/ml per h with estrogen (P < 0.05) versus 32.8 +/- 4.9 ng/ml per h with combination therapy (P < 0.01)], whereas estrogen or combination therapy caused a significant reduction in angiotensin converting enzyme activity [229 +/- 8 nmol/ml per min control versus 189 +/- 10 nmol/ml per min with estrogen (P < 0.05) versus 196 +/- 11 nmol/ml per min with combination therapy (P < 0.05)]. Both of these changes in angiotensin processing enzymes observed during replacement therapy resulted in significant increases in plasma Ang I levels [46.7 +/- 12.5 pg/ml control versus 175.5 +/- 65.9 pg/ml with estrogen (P < 0.05) and 561.7 +/- 373.6 pg/ml with combination therapy (P < 0.05)]. Plasma Ang II and Ang-(1-7) levels were not significantly changed. The mean blood pressure did not change with either treatment. CONCLUSION: These studies reveal that, although chronic estrogen replacement activates renin activity and Ang I, it causes a shift in the processing of angiotensin peptides such that the concurrent reduction in angiotensin converting enzyme activity leads to unchanged plasma Ang II levels. Thus, the potentially harmful effects of estrogen-induced hyperreninemia are balanced by its actions interfering with the formation of the vasoactive product Ang II.

Effects of long-term hormone replacement and of tibolone on choline acetyltransferase and acetylcholinesterase activities in the brains of ovariectomized, cynomologus monkeys.

We examined long-term effects of low and high doses of tibolone, conjugated equine estrogens, and conjugated equine estrogens plus medroxyprogesterone acetate on choline acetyltransferase and acetylcholinesterase activities within different regions of the brain in cynomologus monkeys. All treatments were administered for 2 years. None of the treatments produced significant increases in either choline acetyltransferase or acetylcholinesterase in any of eight brain regions analyzed. In contrast, treatment with conjugated equine estrogens plus medroxyprogesterone acetate, but not conjugated equine estrogens alone, produced significant reductions in both choline acetyltransferase and acetylcholinesterase in the medial septum/diagonal band of Broca compared with untreated controls. Treatment with tibolone also resulted in significant reductions in both choline acetyltransferase and acetylcholinesterase in the medial septum/diagonal band of Broca, and this effect was dose-related. These findings are the first to report the effects of long-term therapies used by postmenopausal women on cholinergic measures in the primate brain. The findings are consistent with recent reports in rats, and suggest that any positive effects of long-term estrogen or hormone replacement therapy on cognitive processes are probably not due to significant effects on choline acetyltransferase or acetylcholinesterase activities.