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.

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.

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.

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.

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.

Estimating prevalence of osteoporosis: examples from industrialized countries.

UNLABELLED: In nine industrialized countries in North America, Europe, Japan, and Australia, country-specific osteoporosis prevalence (estimated from published data) at the total hip or hip/spine ranged from 9 to 38 % for women and 1 to 8 % for men. In these countries, osteoporosis affects up to 49 million individuals. PURPOSE: Standardized country-specific prevalence estimates are scarce, limiting our ability to anticipate the potential global impact of osteoporosis. This study estimated the prevalence of osteoporosis in several industrialized countries (USA, Canada, five European countries, Australia, and Japan) using the World Health Organization (WHO) bone mineral density (BMD)-based definition of osteoporosis: BMD T-score assessed by dual-energy x-ray absorptiometry ≤-2.5. METHODS: Osteoporosis prevalence was estimated for males and females aged 50 years and above using total hip BMD and then either total hip or spine BMD. We compiled published location-specific data, using the National Health and Nutrition Examination Survey (NHANES) III age and BMD reference groups, and adjusted for differences in disease definitions across sources. Relevant NHANES III ratios (e.g., male to female osteoporosis at the total hip) were applied where data were missing for countries outside the USA. Data were extrapolated from geographically similar countries as needed. Population counts for 2010 were used to estimate the number of individuals with osteoporosis in each country. RESULTS: For females, osteoporosis prevalence ranged from 9 % (UK) to 15 % (France and Germany) based on total hip BMD and from 16 % (USA) to 38 % (Japan) when spine BMD data were included. For males, prevalence ranged from 1 % (UK) to 4 % (Japan) based on total hip BMD and from 3 % (Canada) to 8 % (France, Germany, Italy, and Spain) when spine BMD data were included. CONCLUSIONS: Up to 49 million individuals met the WHO osteoporosis criteria in a number of industrialized countries in North America, Europe, Japan, and Australia.

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.

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.

Epidemiology of systemic lupus erythematosus: a comparison of worldwide disease burden.

Systemic lupus erythematosus (SLE) is a disease of multifactorial etiology. Quantifying the burden of SLE across different countries can clarify the role of genetic, environmental and other causative factors in the natural history of the disease, and to understand its clinical and societal consequences. The aim of this study is to summarize data on SLE incidence and prevalence in the USA, Europe, Asia, and Australia. An extensive review of electronic resources (PubMed and MedLine) and medical journals was conducted to identify published studies on SLE incidence and prevalence over the period of 1950-early 2006. Researchers in the countries of interest provided additional information on the epidemiology of SLE. The incidence and prevalence of SLE varies considerably across the countries. The burden of the disease is considerably elevated among non-white racial groups. There is a trend towards higher incidence and prevalence of SLE in Europe and Australia compared to the U.S.A. In Europe, the highest prevalence was reported in Sweden, Iceland and Spain. There are marked disparities in SLE rates worldwide. This variability may reflect true differences across populations, or result from methodological differences of studies. The true geographic, racial, and temporal differences in SLE incidence and prevalence may yield important clues to the etiology of disease.

Multisystem evaluations of the long-term effects of tibolone on postmenopausal monkeys.

This long-term study (2 years) was designed to compare the effects of tibolone (LoTib at 0.05 mg/kg and HiTib at 0.2 mg/kg) with those of conjugated equine oestrogens (CEE) alone (0.042 mg/kg) and CEE continuously combined with medroxyprogesterone acetate (MPA) (0.167 mg/kg) on coronary artery atherosclerosis, bone, mammary gland and uterus in ovariectomised cynomolgus monkeys fed a moderately atherogenic diet. Despite reductions in plasma concentrations of high density lipoprotein cholesterol in tibolone-treated monkeys, there was no exacerbation of coronary artery atherosclerosis. Tibolone was equivalent to, or slightly better than, CEE and CEE + MPA in protecting against postmenopausal bone loss and loss of bone strength. Tibolone also resulted in less stimulation of breast and endometrial tissue compared with CEE and CEE + MPA. In conclusion, the results suggest that tibolone is a cardiovascular-safe treatment that is effective for the prevention of osteoporosis and that may have advantages over CEE or CEE + MPA with regard to endometrial and breast safety.

Influence of estradiol on cortisol secretion in ovariectomized cynomolgus macaques (Macaca fascicularis).

In an investigation of cortisol secretion in fully mature, ovariectomized cynomolgus monkeys (Macaca fascicularis), we compared monkeys that were given either placebo (OVX, n = 26) or 17beta estradiol (E(2 )) (EST, n = 26) in a daily oral dose. Serum cortisol concentrations were measured prior to the experimental manipulation and 3, 6, 9, and 12 months following initiation of treatment. Pretreatment cortisol values did not differ between groups. Assessment of the treatment period values revealed that cortisol concentrations were significantly higher ( approximately 10%) in the EST than in the OVX monkeys. Cortisol also varied significantly across periods of sampling. This time-dependent variation was attributable to elevations in months 6 and 9 (when daylight was generally long), relative to months 3 and 12 (when daylight was relatively short). The modest stimulatory effect of estrogen on corticosteroid production observed in this study is consistent with what has been seen in women, and contrasts with the more robust effects observed in New World monkeys. The possible relationship between season and cortisol secretion observed here has not been previously described in monkeys.

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.

Premenopausal social status and hormone exposure predict postmenopausal atherosclerosis in female monkeys.

OBJECTIVE: To determine whether premenopausal social subordination in female monkeys predicts postmenopausal atherosclerosis, and whether any such effect is altered by chronic exposure to contraceptive steroids or postmenopausal hormone replacement. METHODS: One hundred seventy-seven (177) premenopausal cynomolgus monkeys (Macaca fascicularis) housed in social groups of five or six were fed an atherogenic diet that, for half of the animals, also contained an oral contraceptive (OC). Individuals were judged socially dominant or subordinate based on behavioral observations. After 26 months animals were oophorectomized, biopsied for iliac atherosclerosis, and for the next 36 months were fed one of three atherogenic diets containing soy protein: 1) phytoestrogen-free; 2) phytoestrogens intact; and 3) phytoestrogen-free plus conjugated equine estrogens. Plasma lipids and menstrual cyclicity were also assessed. Finally, all animals were necropsied and the extent of atherosclerosis measured in the coronary and iliac arteries. RESULTS: The interaction of premenopausal social status and OC exposure predicted postmenopausal coronary artery atherosclerosis (P =.02). Subordinate animals not receiving OCs developed twice the coronary atherosclerosis of similarly untreated dominants (P <.01), an outcome mitigated by premenopausal OC exposure (P <.01). These effects occurred across postmenopausal treatment groups and independent of variation in plasma lipids. The same associations were observed in the iliac arteries, and, to a similar extent, both pre- and post-menopausally. Hormone data suggest that untreated premenopausal subordinates may have been estrogen deficient. CONCLUSION: Premenopausal social subordination exacerbates postmenopausal atherosclerosis, an effect possibly mediated by estrogen deficiency and shown here to be prevented by premenopausal OC exposure. These results occur irrespective of postmenopausal treatment.

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.