Surgical menopause impact on vaginal mechanical properties.

Menopause exacerbates visual dysfunction in experimental glaucoma

SummaryA large animal model to study cancellous bone loss and the effect of various therapeutic agents following oestrogen deficiency-related bone loss is needed. Following double fluorochrome labeling at the time of surgery, six and 12 months later, static and dynamic histomorphometry was performed on undecalcified sections of the iliac crests of 16 mature (4 to 5-yearold) ewes following ovariectomy (OVX; n = 8) or sham-operation (Sham; n = 8). We found a slight decrease in bone mass associated with oestrogen deficiency as indicated by a statistically significant increase in trabecular separation (Tb.Sp: +14%, p <0.05) and decrease in wall thickness (W.Th: -10%, p <0.05) in the OVX group. However, at six months, we saw evidence of complete cessation of bone formation in both OVX and Sham animals. At that time there was a statistically significant (p <0.05) decline in the following parameters in both the Sham and OVX animals respectively: osteoid surface (OS: -79%, -77%), osteoid thickness (O.Th: -40%, -30%), flat osteoblasts (Fl.Ob.S: -87%, -94%), cuboidal osteoblasts (Cu.Ob.S: -88%, -65%), osteoid surface as a percentage of the total cancellous bone perimeter (OS/BS: -82%, -80%), osteoblast surface as a percentage of total cancellous bone surface (Ob.S/BS: -94%, -77%), mineralizing surface as a percentage of double labels plus half single labels (MS/OS: -44%, -42%), osteoid volume as a percentage of total area of mineralized bone plus osteoid (OV/TV: -88%, -88%), osteoid as a percentage of mineralized bone (OV/BV: -87%, -86%), osteoid maturation time (Omt: -27%, -35%), bone formation rate, surface referent (BFR/BS: -90%, -87%), bone formation rate, volume referent (BFR/BV: -89%, -86%), and bone formation rate, tissue referent (BFR/TV: -91%, -88%). The data was compared to static and dynamic histomorphometry of three intact ewes (similar age, breed, source) whose biopsies were taken two months after the second biopsies in the present study. The data indicate that there is a slight loss of trabecular bone following OVX but we are unable to explain the dramatic depression of bone turnover with little change in bone resorption. The data resembles the response seen when sheep are given daily doses of methylprednisolone. We speculate that this phenomenon may be a response to endogenous corticosteroid release in a response to stresses of transport, and surgery. A seasonal effect may be another explanation fro these changes, whereas dietary alteration (e. g. poisonous plants), hormonal changes or response to changes in physical activity are unlikely causes.A large animal model to study cancellous bone loss and effect of various therapeutic agents following oestrogen deficiency – related bone loss is needed. Following double fluorochrome labeling at the time of surgery, six and 12 months later, static and dynamic histomorphome-try was performed on undecal-cified sections of the iliac crests of 16 mature (4 to 5-year-old) ewes following ovariectomy (OVX; n = 8) or sham-operation (Sham; n = 8). A slight decrease in bone mass associated with oestrogen deficiency was seen but there was also evidence of complete cessation of bone formation in both OVX and Sham animals. The data resembles the responses seen when sheep are given daily doses of methylpednisolone and may be a response to endogenous corticosteroid release. A seasonal effect may be another explanation for these changes, whereas dietary alteration (e. g. poisonous plants), hormonal changes or response to changes in physical activity are unlikely causes.

Studies were undertaken to determine whether ovariectomy (ovx) would alter the ability of female rats to adapt to low dietary Ca intake by exhibiting an in duodenal active Ca transport. Intact and ovx female rats were fed diets containing 1.5, 0.50, or 0.02% Ca prior to measuring active Ca transport using everted duodenal sacs in vitro. In some experiments, ovx animals were pair-fed to intact animals of the same age consuming the same diet. When ovx animals were allowed to eat ad lib, we found that both growth rate and duodenal active Ca transport increased relative to age-matched, intact controls. However, when growth of ovx animals was maintained at the control rate by pair-feeding, ovx per se did not affect intestinal active Ca transport. Ovx did not alter circulating levels of 1,25-dihydroxyvitamin D (1,25(OH)2D). We found that intact females responded to the low-Ca (0.02%) diet with increased circulating 1,25(OH)2D levels and increased intestinal active Ca transport. Ovx animals exhibited the same increase in circulating concentrations of 1,25(OH)2D in response to low-Ca diet, but did not demonstrate increased duodenal active Ca transport. When ovx animals consumed the diet ad lib, they became larger and exhibited higher Ca transport rates than intact animals fed the high-Ca diet, but there was no difference in Ca transport between ovx animals fed diets containing different Ca contents. The results of these experiments demonstrate that in female rats, the ability to adapt to altered dietary Ca intake is dependent on intact ovarian function and is not necessarily directly related to circulating concentrations of 1,25(OH)2D.

The effect of ovarian steroids and photoperiod on body fat stores and uncoupling protein 2 in the marsupial Sminthopsis crassicaudata

Metabolomics is an important component of system biology complementing genomics, transcriptomis, and proteomics. The project is to determine the effects of 6-month green tea polyphenols (GTP) supplementation on the serum and muscle metabolome in middle-aged ovariectomized (OVX) rats. 39 SD (6-mo-old) rats were sham-operated (n=13) or OVX (n=26). Both sham and OVX animals received no GTP for 6 months. The remaining OVX animals were provided 1.5% w/v GTP in drinking water for 6 months. Endogenous metabolites in serum and muscle were measured using NMR-based metabolomics. Compared to the sham animals, the OVX animals had the following observation in serum: (1) suppressed glucose metabolites and Krebs cycle (decreases in acetate, acetoacetate, acetone, glycerol, glucose, lactate, pyruvate, citrate, succinate and fumarate), (2) altered amino acids metabolites (decreases in alanine, asparagine, glutamine, isoleucine, leucine, valine, tryptophan, lysine, proline, seruine and threonine; increases in glutamate, glycine, phenylalanine and tyrosine), and (3) reduced lipid metabolites (decreases in myo-inositol). The similar trend in serum of OVX animals was also observed in that of muscle of OVX animals. Intriguingly, compared to the OVX animals, 6-month GTP supplementation to the OVX-treated animals reversed the negative impacts of ovariectomy on the middle-aged rats in terms of metabolites of glucose, Kerbs cycle, amino acids, and lipids. The results suggest that chronic GTP supplementation to the OVX animals affects whole-body metabolism, as shown in serum and muscle. Study supported by NIH/NCCAM AT006691.

Objective To compare β-endorphin and allopregnanolone levels and their response to a 2-week oral estrogen treatment with conjugated equine estrogens (CEE) in young ovariectomized (ovx) and in healthy aged female rats. Design Prospective study. Setting Animal laboratory in an academic environment. Animal(s) Twenty-four young ovx and 24 healthy aged female Wistar rats were treated with CEE. Three 8-rat control groups (cycling, ovx, and aged rats) were also included. Intervention(s) Treated rats underwent 14-day oral treatment with three doses of CEE: 0.1 mg/kg/day, 0.5 mg/kg/day, and 2 mg/kg/day. Main outcome measure(s) Cerebral and peripheral β-endorphin and allopregnanolone levels. Result(s) Beta-endorphin levels were lower in aged vs. cycling and ovx control rats. In brain and serum allopregnanolone levels were lower in aged vs. cycling control rats, whereas in the adrenals they were higher in aged vs. cycling animals. In the hypothalamus and anterior pituitary allopregnanolone levels were lower in ovx vs. aged animals. In both ovx and aged animals, CEE treatment reverted the effects of ovariectomy and aging, in a dose-dependent manner. Conclusion(s) Aging is associated with a decrease in cerebral and peripheral β-endorphin and allopregnanolone. In hypoestrogenic rats, CEE treatment restores allopregnanolone and β-endorphin content; this indicates a role for these compounds as neuroendocrine mediators of the effects of estrogens.

To evaluate how aging and estrogen deficiency influence the success rate of Sandblasted Titanium (Ti/SA) implants, the osteointegration of Ti/SA rods was studied in the cortical and trabecular bone of 5 young, 5 aged and 5 ovariectomized (OVX) sheep. The characterization of the host bone by transiliac biopsies of the iliac crest showed a progressive rarefaction of trabecular bone in aged and OVX animals when compared to young ones. A significant reduction, both in cortical and trabecular bone, of the osteointegration rate of Ti/SA rods in the presence of estrogen deficiency compared to young animals was observed, while only a minor reduction was observed in aged animals. These results were confirmed by the pushout test in cortical bone. Bone quality affected the biological response of bone to Ti/SA implants in both trabecular and cortical bone; consequently, strategies to maximize the bone osteogenic properties of osteoporotic patients should be adopted.

The common practice of freezing meniscal allograft tissue is limited due to the formation of damaging ice crystals. Vitrification, which eliminates the formation of damaging ice crystals, may allow the mechanical properties of meniscal allograft tissue to be maintained during storage and long-term preservation. The primary objective of this study was to investigate the differences between fresh, frozen, and vitrified porcine lateral menisci examining compressive mechanical properties in the axial direction. Unconfined compressive stress-relaxation testing was conducted to quantify the mechanical properties of fresh, frozen and vitrified porcine lateral menisci. The compressive mechanical properties investigated were peak and equilibrium stress, secant, instantaneous and equilibrium modulus, percent stress-relaxation, and relaxation time constants from three-term Prony series. Frozen menisci exhibited inferior compressive mechanical properties in comparison with fresh menisci (significant differences in peak and equilibrium stress, and secant, instantaneous and equilibrium modulus) and vitrified menisci (significant differences in peak stress, and secant and instantaneous modulus). Interestingly, fresh and vitrified menisci exhibited comparable compressive mechanical properties (stress, modulus and relaxation parameters). These findings are significant because (1) vitrification was successful in maintaining mechanical properties at values similar to fresh menisci, (2) compressive mechanical properties of fresh menisci were characterized providing a baseline for future research, and (3) freezing affected mechanical properties confirming that freezing should be used with caution in future investigations of meniscal mechanical properties. Vitrification was superior to freezing for preserving compressive mechanical properties of menisci which is an important advance for vitrification as a preservation option for meniscal allograft transplantation.

Monitoring individual morphological changes over time in ovariectomized rats by in vivo micro-computed tomography

The androgenic anabolic steroid nandrolone decanoate prevents osteopenia and inhibits bone turnover in ovariectomized cynomolgus monkeys

Reduced estrogen levels occurring during menopause in woman are accompanied by a variety of disorders, e. g., hot flushes, depressions, osteoporosis, increase of body weight, and reduced movement drive. In this study we investigated the combined effects of physical activity, estradiol substitution, and a phytoestrogen-rich diet on bone mineral density, increase of body weight, and movement drive in an animal model. Ovariectomized (OVX) female Wistar rats were either fed an isoflavone-rich diet (IRD) or substituted with 17beta-estradiol (E2) for 3 months. Sham-operated rats (Sham) and vehicle-treated OVX animals served as controls. One half of the animals had the opportunity of voluntary wheel running. OVX rats displayed an eight times lower movement activity than Sham animals. E2 treatment, but not IRD, significantly increased the movement activity of OVX rats. During 3 months the lowest increase of body weight was observed in Sham animals, the highest rate in OVX animals. Along with running activity E2 treatment, but not IRD, also lowered the increase of body weight significantly compared to OVX animals. Bone mineral density (BMD) in the trabecular area of the tibia was strongly reduced in OVX rats compared to Sham animals. In contrast to IRD, E2 substitution resulted in a protection of BMD in this area compared to OVX animals. Our data demonstrate that body weight, movement drive, and BMD are positively influenced by E2. The steroid estrogen acts in the trabecular area of the tibia in a bone-protective manner, increases movement drive and antagonizes the increase of body weight. All these effects could not be observed in animals fed an isoflavone-rich diet.

Parity is the leading risk factor for the development of pelvic organ prolapse. To assess the impact of pregnancy and delivery on vaginal tissue, researchers commonly use nonhuman primate (NHP) and rodent models. The purpose of this study was to evaluate the ewe as an alternative model by investigating the impact of parity on the ewe vaginal mechanical properties and collagen structure. Mechanical properties of 15 nulliparous and parous ewe vaginas were determined via uniaxial tensile tests. Collagen content was determined by hydroxyproline assay and collagen fiber thickness was analyzed using picrosirius red staining. Outcome measures were compared using Independent samples t or Mann-Whitney U tests. ANOVA (Gabriel's pairwise post-hoc test) or the Welch Alternative for the F-ratio (Games Howell post-hoc test) was used to compare data with previously published NHP and rodent data. Vaginal tissue from the nulliparous ewe had a higher tangent modulus and tensile strength compared with the parous ewe (p < 0.025). The parous ewe vagina elongated 42 % more than the nulliparous ewe vagina (p = 0.015). No significant differences were observed in collagen structure among ewe vaginas. The tangent modulus of the nulliparous ewe vagina was not different from that of the NHP or rodent (p = 0.290). Additionally, the tangent moduli of the parous ewe and NHP vaginas did not differ (p = 0.773). Parity has a negative impact on the mechanical properties of the ewe vagina, as also observed in the NHP. The ewe may serve as an alternative model for studying parity and ultimately prolapse development.

Stimulation and inhibition of bone formation: use of peripheral quantitative computed tomography in the mouse <i>in vivo</i>

The long-time stress relaxation was examined for poly(styrene)-poly(ethylene- co-butylene)-polystyrene triblock copolymer with asymmetric composition in the microphase separated state. Stress relaxation data from a parallel plate rheometer were extended to very long times by using a newly built compression instrument. Three properties were measured, the relaxation time spectrum, the equilibrium modulus, and the instantaneous modulus. Relaxation experiments over several months (without zero drift) allowed determination of extremely long relaxation times as found in soft solids and in liquids near the gel point. In this way, we can distinguish solid from liquid behavior within the experimental time frame. The BCC lattice structure of the test polymer behaves as liquid except at low temperature where an equilibrium modulus was observed in an experiment that lasted over a period of 4 months. The corresponding instantaneous modulus was observed to be constant for the same material and for the same time period.

Comparison of single-phase isotropic elastic and fibril-reinforced poroelastic models for indentation of rabbit articular cartilage