Endothelial dysfunction and menopause: is exercise an effective countermeasure?

Cardiovascular disease is the leading cause of death in women. There is a dramatic rise in risk factors for cardiovascular disease during the menopausal transition that is independent of aging. Endothelial dysfunction is an early hallmark of developing cardiovascular disease and has been shown to increase across the stages of menopause. Exercise is considered one of the most effective lifestyle therapies to maintain and improve endothelial function. However, accumulating evidence suggests that exercise does not have the same benefit on endothelial function in menopausal women as it does in other populations, and factors associated with menopause likely influence the endothelial responsiveness to exercise. This review will detail the current available evidence on endothelial dysfunction, exercise, and menopause, including mechanisms that may mediate the accumulating endothelial dysfunction in women with menopause, the impact of exercise on endothelial function in women, and whether regular exercise is an effective therapeutic and prevention strategy to maintain endothelial function with menopause. We conclude that the effect of exercise on endothelial function differs according to menopausal stage and cardiovascular disease risk burden. Finally, we will address critical gaps in the literature with the goal of identifying future research directions to improve healthy aging in women.

The effects of aerobic training and age on plasma sICAM-1.

Chronic low-grade systemic inflammation plays a role in the development of cardiovascular (CV) disease. Habitual endurance exercise training reduces the risk of CV disease in part through anti-inflammatory mechanisms. The purpose of this study was to investigate the effects of age, endurance training status, and their interaction on pro-inflammatory plasma cytokines involved in the pathogenesis of CV disease. Subjects were BMI-matched young (25±3 years; endurance trained: n=9, sedentary: n=11) and older (62±5 years; endurance-trained: n=12, sedentary: n=11) men. Plasma cytokine concentrations were determined by multiplex cytometric bead assay. Soluble intercellular adhesion molecule-1 (sICAM-1) levels were 40% higher in sedentary older men compared to young sedentary subjects (P=0.048), but they were not different between the young and older trained men. Furthermore, sICAM-1 levels were negatively correlated with maximal oxygen uptake (V˙O2max; r= - 0.38, P=0.01) across all subjects. There were no significant differences among the groups in plasma concentrations of monocyte chemoattractant protein-1 (MCP-1), soluble tumor necrosis-α receptor (sTNFR), soluble CD40 ligand (sCD40L), or resistin. We conclude that habitual endurance training is associated with an attenuated age-related increase in plasma sICAM-1.

Effect of veneering technique on the fracture resistance of zirconia fixed dental prostheses.

To compare the fracture resistance of zirconia 3-unit posterior fixed dental prostheses (FDPs) frameworks veneered with different veneering materials and techniques before and after artificial ageing. Forty-eight zirconia 3-unit FDPs, representing a missing first molar, were adhesively cemented on human teeth. The zirconia frameworks were randomly distributed according to the veneering materials and techniques into three groups, each containing 16 samples: group LV (layering technique/Vintage ZR), group LZ (layering technique/ZIROX) and group PP (CAD/CAM and press-over techniques/PressXZr). Half of each group was artificially aged through dynamic loading and thermocycling to simulate 5 years of clinical service. Afterwards, all specimens were tested for fracture resistance using compressive load. An analysis of variance (anova) was used to assess the effect of veneering ceramic and artificial ageing on fracture resistance (P < 0·05). Except for one minor cohesive chipping in group LV1, all specimens survived artificial ageing. The mean fracture resistance values (in Newton) of different non-aged (± s.d.)/aged (± s.d.) groups were as follows: LV0 2034 (± 401)/LV1 1625 (± 291); LZ0 2373 (± 718)/LZ1 1769 (± 136); and PP0 1959 (± 453)/PP1 1897 (± 329). Artificial ageing significantly reduced the fracture resistance in groups veneered with the layering technique (P < 0·05), whereas no significant effect was found in specimens veneered with the CAD/CAM and press-over techniques. All tested systems have the potential to withstand occlusal forces applied in the posterior region. The combination of the CAD/CAM and press-over techniques for the veneering process improved the overall stability after artificial ageing, relative to the layering technique.

Nitro-oxidative stress biomarkers in active and inactive men.

Oxidative stress markers are novel factors shown to be related to cardiovascular (CVD) risk. We examined the effects of long-term exercise, age, and their interaction on plasma oxidized LDL (ox-LDL), nitrotyrosine, and myeloperoxidase (MPO) levels, all biomarkers of oxidative stress, and determined their association with plasma nitric oxide (NOx) levels as an index of NO bioavailability. Older (62±2 yr) active men (n=12) who had exercised for >30 years and young (25±4 yr) active men (n=7) who had exercised for >3 years were age- and BMI-matched to older (n=11) and young (n=8) inactive men. Young subjects had lower plasma nitrotyrosine levels than older subjects (P=0.047). Young inactive subjects had higher ox-LDL levels than either the young active (P=0.042) or the older active (P=0.041) subjects. In addition, plasma oxidative stress levels, particularly ox-LDL, were correlated with various conventional plasma lipoprotein-lipid levels, and in older subjects were associated with Framingham risk score (r=0.49, P=0.015). We found no relationships between plasma oxidative stress markers and NOx levels. The findings suggest that a sedentary lifestyle may be associated with higher ox-LDL levels and that the levels of oxidative stress markers are related to levels of other conventional CVD risk factors and overall CVD risk.

Partition of tocopheryl glucopyranoside into liposome membranes studied by fluorescence methods.

Vitamin E is poorly soluble in aqueous solutions. Enhanced physiological activity is expected from synthesized glycosidic tocopherol derivatives. We investigated binding, location and interactions of newly synthesized DL-alpha-tocopheryl beta D glucopyranoside (II) in phosphatidylcholine liposomes using fluorescence emission, anisotropy and lifetime methods. In liposomes emission maximum and fluorescence lifetime of glucoside were similar to those observed in methanol. High fluorescence anisotropy value indicates that tocopheryl glucoside is located in restricted mobility region of the membrane. Thermodynamic calculation indicated efficient partition of (II) into membrane. The energy minimization calculations of electrostatic potential distribution of (II) and solvation energies performed with Gaussian program confirmed strong affinity of glucosidic moiety for ionic interactions and supported proposed model of interactions. The all obtained data indicate that DL-alpha-tocopheryl beta-glucoside is embedded into the membrane interior whereas sugar moiety protrudes above the water/lipid interface of the membrane surface.

Glycosidic moiety changes the spectroscopic properties of dl-alpha-tocopherol in DMSO/water solution and in organic solvents.

In this study we estimated how conjugation with a sugar moiety influences the spectral properties of tocopherol and relate the spectroscopic properties of glycosides to solvent properties such as viscosity and polarity. Spectroscopic properties (absorption, fluorescence, fluorescence anisotropy and fluorescence lifetime) of three dl-alpha-tocopheryl glycosides (dl-alpha-tocopheryl orthoacetate derivative and glycosides of dl-alpha-tocopherol model compounds: 2,2,5,7,8-pentamethyl-6-chromanol and Trolox) were studied in DMSO/water solution. In all investigated compounds dissolved in DMSO/water mixture the absorption and emission maxima were blue-shifted. The fluorescence lifetimes were longer compared with those obtained for the parent compounds, except for the Trolox glucoside, in which it was shorter. The observed effect is connected with an increase in the electronic energy in the ground state due to electron rearrangement in the chromanol system caused by interaction with the sugar moiety. The extent of the spectral shift is related to the sugar moiety substituted at the phenolic oxygen rather than to substitution at the 2a position in the chromanol ring. The fluorescent properties of dl-alpha-tocopheryl glucoside in organic solvents were measured. The Stokes shift was related to the orientational polarizability of the solvents. The study of viscosity suggested two different mechanisms explaining the results observed in a low- and high-viscosity environment. The results indicated the fundamental role of interactions between the chromophore and sugar moiety in a low-viscosity environment. The results obtained at high values of viscosity are discussed in terms of a frictional boundary solvent-solute interaction model.

Gas chromatographic retention indices of trimethylsilyl derivatives of mono- and diglycerides on capillary columns with non-polar stationary phases.

Mono- and diglycerides play an important role in the metabolism of plants and animals. They are usually constitutive elements of complex mixtures and are not always as main components, which considerably hinder the identification of these analytes. This work communicates about a synthesis of a wide range of esters of glycerol and aliphatic C(6)-C(20) acids and presents gas chromatographic characteristics of 32 compounds in the form of the most reproducible parameters-linear-programmed retention indices on high-performance capillary columns with non-polar stationary phases. The article also presents mass spectra for a series of those glycerides which were not characterized earlier by these parameters.

The cleavage of vitamin E galactoside in the rat tissue homogenates.

The stability of alpha-tocopheryl beta-galactoside in the presence of endogenous galactosidases in selected tissue homogenates (liver, kidney, ileum and brain) was estimated. High degree release of alpha-tocopherol from alpha-tocopheryl beta-galactoside in tissues of ileum, kidney and brain was observed (82%, 75% and 72%, increase above endogenous alpha-tocopherol, respectively). A possible enzymatic mechanism of the galactoside decomposition was proposed.

[Stereolithography as an additive technique in dentistry]. / Stereolithographie als generatives Verfahren in der Zahntechnik.

3D-CAD constructions offer the application of CAM-techniques for the fabrication of dental restorations. CNC-units are generally used for milling and grinding. However, the application of new additive working technology enables the construction of 3D-solid models. In the field of rapid prototyping (RP), the process of "three-dimensional printing" allows the fabrication of patterns for the lost-wax casting technique from materials such as wax or resin. This paper describes the use of a light-curing fluid resin in combination with a UV-light projection in means of stereolithography (SL). The presented CAM unit (Perfactory, DeltaMed, D-Friedberg) reduces processing times of large casting patterns by using CAD constructions. This concept focuses on the advancement of the common casting technique in dental technology by application of CAD/CAM technology.

Determinants of erythropoietin release in response to short-term hypobaric hypoxia.

We measured blood erythropoietin (EPO) concentration, arterial O(2) saturation (Sa(O(2))), and urine PO(2) in 48 subjects (32 men and 16 women) at sea level and after 6 and 24 h at simulated altitudes of 1,780, 2,085, 2,454, and 2,800 m. Renal blood flow (Doppler) and Hb were determined at sea level and after 6 h at each altitude (n = 24) to calculate renal O(2) delivery. EPO increased significantly after 6 h at all altitudes and continued to increase after 24 h at 2,454 and 2,800 m, although not at 1,780 or 2,085 m. The increase in EPO varied markedly among individuals, ranging from -41 to 400% after 24 h at 2,800 m. Similar to EPO, urine PO(2) decreased after 6 h at all altitudes and returned to baseline by 24 h at the two lowest altitudes but remained decreased at the two highest altitudes. Urine PO(2) was closely related to EPO via a curvilinear relationship (r(2) = 0.99), although also with prominent individual variability. Renal blood flow remained unchanged at all altitudes. Sa(O(2)) decreased slightly after 6 h at the lowest altitudes but decreased more prominently at the highest altitudes. There were only modest, albeit statistically significant, relationships between EPO and Sa(O(2)) (r = 0.41, P < 0.05) and no significant relationship with renal O(2) delivery. These data suggest that 1) the altitude-induced increase in EPO is "dose" dependent: altitudes > or =2,100-2,500 m appear to be a threshold for stimulating sustained EPO release in most subjects; 2) short-term acclimatization may restore renal tissue oxygenation and restrain the rise in EPO at the lowest altitudes; and 3) there is marked individual variability in the erythropoietic response to altitude that is only partially explained by "upstream" physiological factors such as those reflecting O(2) delivery to EPO-producing tissues.

Synthesis and hypolipidemic and antiplatelet activities of alpha-asarone isomers in humans (in vitro), mice (in vivo), and rats (in vivo).

A series of alpha-asarone isomers was synthesized and investigated for their hypolipidemic and antiplatelet activity. Considering the hypolipidemic activity in rats at a dose of 80 mg/kg/day, some isomers were more potent than clofibrate at 150 mg/kg. Compound 3 was one of the most active agents elevating the HDL cholesterol level by 56% and lowering the LDL cholesterol level by 46.8% in rats after 7 days of administration. The activities of the platelet aggregation test in vitro were significant but lower than those of the reference substances (indomethacine and acetylsalicylic acid). In the pulmonary thromboembolic in vivo test in mice, two compounds (alpha-asarone (6) and compound 4) produced significant antithrombotic effects at 100 mg/kg, namely 44% and 52% protection against lung microembolia, respectively. alpha-Asarone derivatives form a new group of potential hypolipidemic and/or antithrombotic agents. The compounds 3, 4, and 6 may serve as lead substances whose structural modifications may result in original drugs.

13C CP MAS NMR study of 6-O-(beta-D-glucopyranosyl)- and 6-O-(beta-D-mannopyranosyl)-d-alpha-tocopherols.

13C NMR CP MAS data for three glycosyl alpha-tocopherol derivatives are reported. The values of delta = delta(solution) - delta(solid state) provided information about rigid and conformationally flexible fragments of alpha-tocopherol molecule and the sugar moieties.

Strength and mode of failure of single implant all-ceramic abutment restorations under static load.

The strength and mode of failure of three different designs of custom-made all-ceramic implant abutments fabricated by milling of In-Ceram sintered ceramic blocks were compared with the conventional CeraOne system under static load. Four test groups were formed with different locations of abutment screws. In three test groups, In-Ceram crowns were fabricated for placement on the all-ceramic abutments, and in one test group, a veneer porcelain was fired directly on the abutment; crowns in the control group were fabricated using the CeraOne system. Ten-mm-long Brånemark implants were placed into a brass block that allowed loading at a 30-degree angle to the long axis. The test group in which the veneer porcelain was fired directly on the all-ceramic abutments was the weakest, and it showed fractures at a mean value of 236 N. The fracture strength of the three other test groups was dependent on the extension of the crown margin relative to the location of the screw head. The test group that had the screw on the top compressing the entire ceramic abutment showed a mean value of 422 N that was similar to the results that were achieved with the CeraOne system (427 N). The weakest link in the all-ceramic single implant restorations was the abutment screw in which the bending began at approximately 190 N.

[Thrombolytic therapy in arterial thrombosis producing acute ischemia of the lower limbs]. / Leczenie trombolityczne zakrzepicy tetnic powodujacej ostre niedokrwienie konczyn dolnych.

Efficiency of the thrombolytic therapy in the acute arterial thrombosis (producing an acute ischemia of the lower limbs) with streptokinase has been assessed in 35 patients treated in the selected departments of vascular surgery in Poland. Complete recovery has been noted in 9 patients (25.7%) in whom limb functioning with detectable peripheral pulse have been restored. An improvement has been achieved in 12 (34.3%) patients and moderate result in 4 (11.4%) patients. The limb has been amputated in 7 (20%) patients, and 3 patients (8.6%) died. Similar results have been observed in case of ischemia of duration period below 12 hours, between 12 and 24 hours, and between 24 and 72 hours. The results have been worse when thrombolytic therapy was introduced after 72 hours.