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We report a computational study of the structural and energetic properties of water clusters and singly-charged water cluster anions containing from 20 to 573 water molecules. We have used both a classical and a quantum description of the molecular degrees of freedom. Water intra and inter-molecular interactions have been modelled through the SPC/F model, while the water-excess electron interaction has been described via the well-known Turi-Borgis potential. We find that in general the quantum effects of the water degrees of freedom are small, but they do influence the cluster-size at which the excess electron stabilises inside the cluster, which occurs at smaller cluster sizes when quantum effects are taken into consideration.

We report the first study on the thermal behavior of the stiffness of individual carbon nanotubes, which is achieved by measuring the resonance frequency of their fundamental mechanical bending modes. We observe a reduction of the Young's modulus over a large temperature range with a slope -(173±65)  ppm/K in its relative shift. These findings are reproduced by two different theoretical models based on the thermal dynamics of the lattice. These results reveal how the measured fundamental bending modes depend on the phonons in the nanotube via the Young's modulus. An alternative description based on the coupling between the measured mechanical modes and the phonon thermal bath in the Akhiezer limit is discussed.

Introduction and Aims: An inlet patch (IP) is the presence of gastric columnar epithelium outside of the stomach. No studies have been conducted in Mexico on that pathology. The aim of the present study was to determine the prevalence of esophageal IP and the clinical characteristics of the patients that present it., Materials and Methods: A cross-sectional study was conducted that included consecutive patients referred for endoscopy within the time frame of September 2015 to May 2016. The patients answered a questionnaire, and high-definition endoscopy with digital chromoendoscopy was performed. The prevalence of IP was identified. The chi-square test was used to compare the clinical characteristics between patients that presented with esophageal IP and those without it., Results: A total of 239 patients were included in the study. Their mean age was 53 years, and 130 (54.4%) were women. IP was found in 26 patients (10.9%), 15 of whom were men (57.7%). The main reason for referral to endoscopy was gastroesophageal reflux disease, present in 69.2% of the patients with IP and in 55.9% without IP (p=.19). The most common symptoms were heartburn and regurgitation. The former was present in 69.2% of the patients with IP and in 59.1% without IP (p=.32), and the latter was present in 65.4% of the patients with IP and 69.1% without IP (p=.7). Extraesophageal manifestation distribution was: cough in 46.2% of the patients with IP and 38% without IP (p=.45) and dysphonia in 54% with IP and 47% without IP (p=.53). Twenty-three percent of the patients with IP had Barrett's esophagus, as did 23% without IP (p=.99)., Conclusions: The prevalence of IP was high. The primary referral diagnosis was gastroesophageal reflux disease. No differences were found in relation to symptoms or the presence of Barrett's esophagus between the patients with and without IP., (Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.)

We consider the problem of how a condensed molecular system approaches equilibrium, focusing on the particular case of water. We show, by means of extensive molecular dynamics simulations, that the existence of different types of degrees of freedom affects the dynamics of equilibration, and this influence is made most obvious in the system's temperature. When equipartition of energy does not hold in the initial, nonequilibrium state, the instantaneous temperature can be up to a few degrees lower than that observed under equipartition conditions, resulting in a Mpemba-like effect. Though our study considers water in particular, our findings apply more generally to condensed molecular systems.

Background: There are no studies on the factors associated with gastroesophageal reflux disease (GERD) relapse in primary care patients., Aim: To identify the risk factors associated with GERD relapse in primary care patients that responded adequately to short-term treatment with a proton pump inhibitor., Patients and Methods: A cohort study was conducted that included GERD incident cases. The patients received treatment with omeprazole for 4 weeks. The ReQuest questionnaire and a risk factor questionnaire were applied. The therapeutic success rate and relapse rate were determined at 4 and 12 weeks after treatment suspension. A logistic regression analysis of the possible risk factors for GERD relapse was carried out., Results: Of the 83 patient total, 74 (89.16%) responded to treatment. Symptoms recurred in 36 patients (48.64%) at 4 weeks and in 13 patients (17.57%) at 12 weeks, with an overall relapse rate of 66.21%. The OR multivariate analysis (95% CI) showed the increases in the possibility of GERD relapse for the following factors at 12 weeks after treatment suspension: basic educational level or lower, 24.95 (1.92-323.79); overweight, 1.76 (0.22-13.64); obesity, 0.25 (0.01-3.46); smoking, 0.51 (0.06-3.88); and the consumption of 4-12 cups of coffee per month, 1.00 (0.12-7.84); citrus fruits, 14.76 (1.90-114.57); NSAIDs, 27.77 (1.12-686.11); chocolate, 0.86 (0.18-4.06); ASA 1.63 (0.12-21.63); carbonated beverages, 4.24 (0.32-55.05); spicy food 7-16 times/month, 1.39 (0.17-11.17); and spicy food ≥ 20 times/month, 4.06 (0.47-34.59)., Conclusions: The relapse rate after short-term treatment with omeprazole was high. The consumption of citrus fruits and NSAIDs increased the possibility of GERD relapse., (Copyright © 2016 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.)

We describe a robust and efficient chain-of-states method for computing Minimum Energy Paths (MEPs) associated to barrier-crossing events in poly-atomic systems, which we call the acceleration method. The path is parametrized in terms of a continuous variable t ∈ [0, 1] that plays the role of time. In contrast to previous chain-of-states algorithms such as the nudged elastic band or string methods, where the positions of the states in the chain are taken as variational parameters in the search for the MEP, our strategy is to formulate the problem in terms of the second derivatives of the coordinates with respect to t, i.e., the state accelerations. We show this to result in a very simple and efficient method for determining the MEP. We describe the application of the method to a series of test cases, including two low-dimensional problems and the Stone-Wales transformation in C60.

Saturated and trans fatty acids have been associated with the risk to develop cardiovascular diseases. However, health-promoting effects are associated with consumption of anhydrous milk fat (AMF) and ruminant trans fatty acids, such as conjugated linoleic acid (CLA) and vaccenic acid (VA) contained in the lipid fraction of milk and dairy products. The purpose of this study was to evaluate the effect of AMF naturally enriched with CLA and VA in spontaneously hypertensive rats (SHR), using sterculic oil to inhibit the conversion of VA into CLA. The administration of AMF to SHR during 7 weeks exerted beneficial effects on cardiovascular risk biomarkers (reduction of insulin, blood lipids, increase of adiponectin). When sterculic oil was included, some parameters were further ameliorated (reduction of insulin, increase of adiponectin). Sterculic oil alone reduced body weight and adiposity, and improved blood pressure, adiponectin and triglyceride levels.

We report large-scale first-principles simulations of melting of four different phases of Li at pressures ranging from 0 to 50 GPa. We find excellent agreement with existing experimental data at low pressures, and confirm that above 10 GPa the melting line develops a negative slope, in parallel to what occurs for Na at 30 GPa. Surprisingly, our results indicate that the melting temperature of the bcc phase is always higher than that of fcc Li, suggesting the intriguing possibility of the existence of a narrow field of bcc stability separating the fcc and liquid phases, as predicted by Alexander and McTague [Phys. Rev. Lett. 41, 702 (1978)].

The amphiphillic character, that is, the capacity to simultaneously attract and repel water, has been traditionally reserved to organic molecules such as phospholipids and surfactants, containing both hydrophilic and hydrophobic groups within the same molecule. However, this general concept can be extended to artificial structures such as micrometer-sized particles, the so-called Janus particles, and patterned surfaces. Here we provide an example of an amphiphillic crystalline solid, l-alanine, by combining atomic force microscopy measurements performed on two different cleavage surfaces showing contrasting behaviors when exposed to water vapor, with computer simulations that allow us to clarify the dipolar origin of this behavior. Although we take l-alanine as an example, our results should apply quite generally to dipolar molecular crystals.

The path integral formulation has been combined with several methods to determine free energies of quantum many-body systems, such as adiabatic switching and reversible scaling. These techniques are alternatives to the standard thermodynamic integration method. A quantum Einstein crystal is used as a model to demonstrate the accuracy and reliability of these free energy methods in quantum simulations. Our main interest focuses on the calculation of the melting temperature of Ne at ambient pressure, taking into account quantum effects in the atomic dynamics. The free energy of the solid was calculated by considering a quantum Einstein crystal as reference state, while for the liquid, the reference state was defined by the classical limit of the fluid. Our findings indicate that, while quantum effects in the melting temperature of this system are small, they still amount to about 6% of the melting temperature, and are therefore not negligible. The particle density as well as the melting enthalpy and entropy of the solid and liquid phases at coexistence is compared to results obtained in the classical limit and also to available experimental data.

Although the capacity of recombinant FSH alone to induce folliculogenesis is undisputed, many believe that follicular recruitment in women over 38 years old could be improved by supplementing rFSH with human menopausal gonadotrophin (HMG). The present study sought to determine whether recombinant LH could reproduce the effect of HMG in women over 38 years during ovulation induction. Fifty-eight patients received rFSH (225 IU/day) supplemented with one ampoule of HMG (75 IU of FSH/75 IU of LH/HCG per day) for 5 days. Another 36 patients received rFSH (300 IU/day) supplemented with one ampoule of rLH (75 IU/day), also for 5 days. Both groups of patients received similar amounts of rFSH (1500 IU), LH/HCG (375 IU) and rLH (375 IU) and recruited a similar number of follicles as counted on day 6 (4.07 +/- 3.1 in the HMG group versus 3.7 +/- 3.2 in the LH group respectively) or on the day that human chorionic gonadotrophin (HCG) was indicated (6.5 +/- 2.7 versus 5.8 +/- 2.5 respectively). Ovarian stimulation was shorter, but not significantly so, in the group of patients receiving rFSH + HMG (10.5 +/- 1.7 days) than in the group of patients treated with rFSH +/- rLH (12 +/- 1.8 days). Significantly more MII oocytes were seen in the group treated with rFSH + rLH than in the group treated with rFSH + HMG (93.1 versus 75.3%, P < 0.05). With respect to pregnancy rates, 14/54 (26%) patients receiving rFSH + HMG and 16/34 (47%) patients receiving rFSH + rLH had a positive serum HCG. No significant difference in the number of miscarriages was observed between the two groups. In conclusion, the present results seem to indicate that rLH could be the HMG component that aids early follicular recruitment.

In this Letter we present a calculation of the temperature-pressure phase diagram of Si in a range of pressures covering from -5 to 20 GPa and temperatures up to the melting point. The phase boundaries and triple points between the diamond, liquid, beta-Sn, and Si34 clathrate phases are reported. We have employed efficient simulation techniques to calculate free energies and to numerically integrate the Clausius-Clapeyron equation, combined with a tight-binding model capable of an accuracy comparable to that of first-principles methods. The resulting phase diagram agrees well with the available experimental data.

Background: We aimed to assess the efficacy of a GnRH antagonist in intrauterine insemination (IUI) cycles to increase number of mature ovulatory follicles and pregnancy rates., Methods: Prospective randomized study. Women (18-38 years old) with primary/secondary infertility were included. Eighty-two patients were randomly assigned to controlled ovarian stimulation (COS) consisting of rFSH + GnRH antagonist or rFSH alone., Results: A non-significant increase in the total amount of rFSH was seen in the GnRH antagonist group (707+/-240 IU) with respect to the control group (657+/-194 IU). The number of mature follicles (> or =16 mm) was significantly higher in the GnRH antagonist group than in the control group (2.4+/-1.4 versus 1.7+/-1.2, P<0.05). Pregnancy rates were significantly increased in the group of patients receiving the GnRH antagonist (38%) compared to the control group (14%). The only non-single pregnancy (triplets) occurred in the antagonist group., Conclusions: In this preliminary study, adding the GnRH antagonist to the COS protocol for IUI cycles significantly increased pregnancy rates. Nevertheless, these results may not be associated directly with the antagonist itself but with the fact that more mature ovulatory follicles are present by the day of the hCG. Finally, the risk for multiple gestations needs to be carefully evaluated.

We studied the effect of boron supplement on experimental osteopenia caused by strenuous exercise in 93- d-old female Wistar rats. A control group of 15 rats was not manipulated. The exercise group of 30 rats was divided into 2 groups of 15 rats each, one that was fed a diet supplemented with 50 mg/kg of boron in the form of Na(2)B(4)O(7), and other that, did not receive a boron supplement. The length and weight were determined in the femur and fifth lumbar vertebra and the bone mineral content and density were assessed through densitometry, and trabecular bone volume, trabecular number, trabecular thickness, and trabecular separation with histomorphometry. The femur length and weight, and vertebra weight, and femur and vertebra bone mineral content and density were significantly lower and the trabecular separation was higher in the exercise group than in the others (p < 0.005 in all). The femur weight, bone mineral content and density, trabecular bone volume and trabecular thickness, were significantly higher in the exercise plus boron group (p < 0.005 to 0.0001). It was concluded that boron preserves bone mass in rats that have been exposed to intense exercise.

Weight and gonadal status are the main determinants of bone mass in women. Because of this it is important to study which influences it more. The effect of weight (expressed as body mass index, BMI) and gonadal status of women on total-body bone mineral content (TBBMC) and regional bone mineral content (BMC) was investigated. A total of 373 normal women (mean age 48.9 +/- 13.4 years) were studied: 171 postmenopausal women (mean age 59.3 +/- 9.5 years; years since menopause 11.3 +/- 6.7 years); 76 perimenopausal women (mean age 48.9 +/- 2.2 years); and 126 premenopausal women (mean age 34.7 +/- 7.4 years). In all the women, TBBMC and regional BMC were determined by dual-energy X-ray absorptiometry. Also biochemical markers of bone metabolism (total alkaline phosphatase and tartrate-resistant acid phosphatase) and serum estrone and estradiol were determined. When the women were stratified by gonadal status and BMI, thin women (BMI <20 kg/m2) had significantly lower TBBMC and regional BMC, lower gonadal steroid concentration and higher levels of biochemical markers than overweight (BMI 25-30 kg/m2) and obese (BMI >30 kg/m2) women, regardless of gonadal status. Overweight and obese women had findings suggestive of increased parathyroid activity, but greater bone mass. Weight rather than gonadal steroid concentration is the main determinant of bone mass in women regardless of gonadal status.

Objective: After tubal ligation, normal bone mass in the presence of gonadal deficit has been reported. These incongruent results motivated us to examine the topic., Study Design: Bone mass was assessed by densitometry and ultrasonography 60 days after surgery on 100-day-old female Wistar rats. Fifteen Wistar rats with uterine horn ligation (TL) were compared with 15 unoperated, 15 with a sham uterine horn ligation (Sham-TL), and 15 ovariectomized (OVX), using ANOVA and a correlation test to determine the relations between results., Results: Femoral and vertebral bone mass were significantly lower in the OVX y TL groups than in unoperated and controls groups (P<0.0001)., Conclusions: Our study revealed significantly lower axial and peripheral bone mass in rats with uterine horn ligation.

Background: A study was carried out over a 24-month interval to determine if an initial measurement of serum tartrate-resistant acid phosphatase would be predictive of bone mass loss quantified by dual-energy X-ray absorptiometry, as total bone mineral content and total bone mineral content corrected for weight., Design: Sixty-two women were studied (at onset: mean age 59.7 +/- 8.9 years, 10.8 +/- 8.8 years since menopause; at conclusion: mean age 61.9 +/- 8.8 and 13.0 +/- 8.7 since menopause)., Results: A paired Wilcoxon test showed a small, but significant, increase in weight (P < 0.05) and decrease in height (P < 0.05). Total bone mineral content and total bone mineral content corrected for weight decreased (P < 0.005 and 0.0001, respectively). Serum tartrate-resistant acid phosphatase increased (P < 0.005). Single-regression analysis showed that the per cent bone mass loss observed between the first and second body bone mineral content measurements correlated negatively with the first serum tartrate-resistant acid phosphatase determination (r = -0.62, P < 0.0001). Changes in tartrate-resistant acid phosphatase correlated negatively with changes in total bone mineral content (r = -0.79, P < 0.0001). In a multiple regression analysis of per cent change in bone mass against initially important variables such as age, years since menopause, weight, and tartrate-resistant acid phosphatase, only tartrate-resistant acid phosphatase was significant (P < 0.0001). The sensitivity and specifity of tartrate-resistant acid phosphatase for evaluating bone loss were 86% and 78%, respectively, and the area under the curve was of 0.83 (95% CI 0.71-0.95)., Conclusion: These results show that a simple measurement of serum tartrate-resistant acid phosphatase can help to predict the potential rate of bone mass loss in women.

Study Design: A cross-sectional study., Objective: To clarify the existing controversy with regard to whether paraplegic patients suffer a loss of bone mass in the upper limbs., Setting: Madrid, Spain., Methods: We evaluated bone mass by phalangeal ultrasonography in 35 male patients with paraplegia (mean age 49+/-12 years), and 25(OH)D3 and PTH to exclude the presence of osteomalacia and secondary hyperparathyroidism. Spasticity was evaluated according to the Ashworth scale. Patients were compared with a control group of 35 healthy male subjects (mean age 48+/-13 years)., Results: The patients had lower 25(OH)D3 levels and amplitude-dependent speed of sound (Ad-SOS) than controls (both P<0.001), and higher PTH levels (P<0.05). There was a statistically significant negative association between PTH and 25(OH)D3 levels (r=-0.52, P<0.0001, CI -0.73 to -0.22) and between 25(OH)D3 and injury duration (r=0.34, P<0.05, CI -0.60 to -0.01). There was no correlation between Ad-SOS values, levels of PTH or 25(OH)D3, and the injury duration. No significant difference in Ad-SOS values was found in patients grouped according to low-to-normal 25(OH)D3 level or according to normal-to-high PTH level. There were no differences in relation to muscle tone. Only alkaline phosphatase and tartrate-resistant acid phosphatase levels were higher in patients than in controls (both P<0.001)., Conclusion: Paraplegic patients had a loss of phalangeal bone mass that was unrelated to the levels of vitamin D or PTH, or to muscle tone, so it seems to be related to increased bone resorption rather than to deficient bone formation.

Background and Aims: To determine bone mass using quantitative phalangeal bone ultrasound in young coeliac patients after a long-term gluten-free diet., Subjects: A total of 99 patients with coeliac disease (CD) (52 girls, mean age 15.5 +/- 9.7 years; 47 boys, mean age 14.4 +/- 8.4 years) and 44 healthy subjects matched for age, weight and height (26 girls, mean age 18.4 +/- 9.9 years; 18 boys, mean age 16.3 +/- 11.2 years) were included in the study., Methods: Bone status was assessed using an ultrasound device that measures amplitude-dependent speed of sound (Ad-SoS) in metres per second. Measurements were made on the phalanges (II-V) of the non-dominant hand, and an average value was computed. Nutrient intake was assessed using a 7-day record., Results: Analysis of variance (ANOVA) and the unpaired t-test showed that the intake of phosphates (P < 0.05), proteins, fat and carbohydrates (P < 0.005 in all) was higher in patients than in controls. No significant difference in Ad-SoS was found between patients and controls (95% CI -10.9 to 60.6) in the overall group, in girls or boys, or in patients following a gluten-free diet strictly or partially. In the patients, only age (beta 4.01, 95% CI 1.84-6.16, P < 0.0005) and weight (beta 2.62, 95% CI 1.53-3.70, P < 0.0001) showed a significant positive relation with Ad-SoS., Conclusions: In patients with CD, gluten-free diet and increased nutritional intake were accompanied by normal bone mass values as determined by ultrasound on phalanges.

Rationale and Objectives: In an experimental study in 40 rat femurs, the authors correlated the amplitude-dependent speed of bone ultrasound (Ad-SOS) with the bone mineral content and density and with the bone trabecular connectivity: trabecular bone volume, trabecular number, trabecular thickness, and trabecular separation to evaluate and compare the usefulness of the Ad-SOS to determine bone quantity and/or quality., Methods: Bone mineral content and density were determined with dual-energy x-ray absorptiometry. Trabecular connectivity was determined with histomorphometric techniques., Results: There was a strong correlation between the Ad-SOS and the other parameters studied, with a particularly high positive correlation with trabecular bone volume and trabecular thickness, and an inverse correlation with trabecular separation. The correlation was weaker with the bone mineral content and bone mineral density and with the trabecular number. For the trabecular separation, the correlation was significant in all cases, but it was negative., Conclusions: Bone ultrasound, in this case Ad-SOS, defines the quality of the bone in terms of trabecular architecture rather than bone density; however, this conclusion is valid only for the rat femur model that the authors used.

We observed the effects of sodium bicarbonate supplement on bone mass in rats on strenuous treadmill training. Sixty female Wistar rats (93-days-old; mean initial weight 261 +/- 16 g) were studied. One group of 15 rats was killed at the beginning of the experiments (basal control group), while another group of 15 rats was not manipulated (Exer-NaB-). Another group of 15 rats was exercised but did not receive sodium bicarbonate (Exer+NaB-), while the final group of 15 rats exercised and received sodium bicarbonate (Exer+NaB+) at a dose of 0.05 mg/kg/day, administered by esophageal catheter on exercise days. These rats were killed at the end of 11 weeks. Femoral and vertebral length, weight, and bone mineral content (BMC) and density (BMD) were measured. According to ANOVA with the Tukey-Kramer test, femur length and weight, vertebral weight, femur BMC and BMD, vertebral BMC and BMD and the ratio between femur and vertebral BMC and final body weight, and plasma bicarbonate were lower in the basal control and Exer+NaB- groups than in the two other groups (P < 0.005-0.0001). Overall, there was a positive correlation between femur and vertebral BMC and femur BMC and length (P < 0.0001 for all). Only in the Exer+NaB- group was there a positive association between plasma bicarbonate levels and femur length (r = 0.78; P < 0.0005). Our study demonstrates the adverse effects of strenuous exercise on bone, and the usefulness of sodium bicarbonate supplements in preventing and minimized these effects.

Aims: The influence of eating habits on bone mass is a controversial topic. We have use ultrasound to search for the relationships between nutrients and bone density., Methods: A total of 228 women (mean age 48.9 +/- 13.7 years) were studied, and divided according to their gonadal status (pre-, peri- and postmenopausal women). The dietary intake was recorded for 7 days, and their bone mass was measured by phalangeal amplitude-dependent speed of sound (Ad-SOS). ANOVA was made to examine the differences according to gonadal status. To determine the possible correlation between Ad-SOS and nutrient intake, partial correlations, adjusted for important confounding variables, were done., Results: With partial correlations, there was no correlation of Ad-SOS with the nutrients studied here., Conclusion: We find no correlation of bone mass as measured by Ad-SOS with the most common nutrients and trace minerals, either for the participants as a whole or according to gonadal status., (Copyright 2001 S. Karger AG, Basel)

The behavior of phalangeal bone ultrasound was studied, measured by amplitude-dependent speed of sound (Ad-SOS) in meters per second, in 324 normal women (mean age 48.9 +/- 13.7 years) classified by gonadal status (premenopausal, perimenopausal and postmenopausal) and body mass index (BMI, thin, normal, overweight and obese). Ad-SOS differed significantly with gonadal status and BMI (p<0.0001 for all). In the overall group of women, Ad-SOS correlated negatively with age (r=-0.84, p<0.0001), weight (r=-0.16, p<0.005), BMI (r=-0.27, p<0.0001), and tartrate-resistant acid phosphatase concentration (TRAP) (r=-0.35, p<0.0001). The negative correlation remained significant in the groups separated by gonadal status, but to a lesser extent. After adjusting for confounding variables such as age and weight, Ad-SOS was dependent on age (but not on weight or BMI) in the overall group of women and in the gonadal status groups. In conclusion, Ad-SOS values differed significantly with gonadal status and BMI, and correlated negatively with TRAP. The plot of Ad-SOS against age differed significantly with gonadal status as well as BMI.

Objective: The effect of a copper supplement on preventing bone mass loss induced by ovariectomy in rats was investigated., Design: Three groups of fifteen 100-day-old female Wistar rats, each with a mean initial weight of approximately 260 g per animal, were selected for a 30-day experiment. One group of 15 ovariectomized rats was fed a diet supplemented with 15 mg of copper per kilogram of feed. The other two groups: 15 ovariectomized and 15 Sham- ovariectomized rats did not receive the supplement. Morphometric (weight and length) and densitometric studies with dual-energy x-ray absorptiometry were performed on the whole femur and the fifth lumbar vertebra of each animal at the end of the 30-day period., Results: The ovariectomized rat group fed a diet supplemented with copper did not show the bone mass loss at the axial (fifth lumbar vertebra) or peripheral (femur) level that was evidenced in the ovariectomized group., Conclusions: The results of the measurement of axial and peripheral bones show that a supplement of copper may have a potential therapeutic application in the treatment and prevention of involutional osteoporosis.

Objective: This paper studied the influence of several gynecological factors (years since menopause (YSM), age at menarche and gynecological age or reproductive life) simultaneously with anthropometric factors as determinants of bone mass in 189 healthy postmenopausal women., Methods: Bone mass was determined by peripheral quantitative computed tomography., Results: An overall evaluation showed that YSM correlated negatively with trabecular and cortical bone density (BMDTrab and BMDCorti) (P<0.05 in both cases). Age at menarche correlated negatively with BMDCorti (P<0.05) and gynecological age correlated positively with BMDTrab (P<0.05). Classifying the women according to their body mass index (BMI), the YSM correlation persisted in those subjects whose BMI was >25 kg/m(2), and in age at menarche and gynecological age of women whose BMI was <25 kg/m(2) (P<0.05). After separating women according to their age at menarche, their gynecological age and BMI, the only significant difference that persisted was in BMDTrab which was lower in the group with gynecological age <33 years, with a BMI <25 kg/m(2) (P=0.020). Parity and smoking had no impact on our results. By multiple regression, with BMD as the dependent variable and the gynecological factors as independent variables, we only observed significance between YSM and BMDCorti (P<0.005). The same was observed after separating women according to their BMI in the >25 kg/m(2) group (P<0.05)., Conclusions: Our data stress the importance of YSM on BMDTrab and BMDCorti, of age at menarche on BMDCorti and of gynecological age on BMDTrab. However, YSM is the gynecological factor that mainly determines BMD. The differences observed between measurements taken with pQCT and other methods commonly used to estimate bone mass indicate that results obtained with one technique cannot be extrapolated to other methods.

Background: The objective of the study was to evaluate bone mass status (as measured by bone ultrasound) in patients on anticonvulsant therapy, and the influence that Vitamin D administration exerts over it., Materials and Methods: We measured and compared the basal serum levels of 25(OH)D3, parathyroid hormone (PTH), and phalangeal bone ultrasound (Ad-SOS), in 30 adult patients who were taking anticonvulsant drugs, with a control group of similar age and sex. We then gave the patients a large oral dose of 3 mg (120.000 UI) of 25(OH)D3, and repeated the measurements after one month., Results: Basal 25(OH)D3 and Ad-SOS values were significantly lower, and PTH values significantly higher (P< 0.0001 in all), in the patient group. The low Ad-SOS values for the patients were independent of the treatment, but directly related to basal 25(OH)D3 levels (r = 0.45, P<0.01). There was a negative association between PTH and 25(OH)D3 (r = -0.64, P<0.0001), and no correlation between PTH y Ad-SOS (r = -0.20, p NS). After ingestion of the large dose of the vitamin D, the patient group registered a significant (P<0.0001) increase in 25(OH)D3 levels, their Ad-SOS values increased (P<0.0001) nearly to the mean basal value of the control group, and PTH decreased significantly (P<0.0001)., Conclusions: These findings justify the need to assure adequate vitamin D intake in patients being treated with anticonvulsants, independently of the treatment, age, sex, and activity status, in order to prevent osteomalacia.

Objective: The aim of this study was to examine the effect of manganese (Mn) alone and with the addition of copper (Cu) in the inhibition of osteopenia induced by ovariectomy (OVX) in rats. STUDY CONDITIONS: Four lots of 100-day-old female Wistar rats were divided into experimental groups of 15 each. One group received a diet supplemented with 40 mg/kg of Mn per kilogram of feed (OVX+Mn). The second group received the same diet as the first, but with an additional 15 mg/kg of copper (OVX+Mn+Cu). The third group of 15 OVX and the fourth group of 15 Sham-OVX received no supplements. At the conclusion of the 30-day experiment, the rats were slaughtered and their femurs and fifth lumbar vertebrae were dissected. Femoral and vertebral length were measured with caliper and bones were weighed on a precision balance. The bone mineral content (BMC) and bone density (BMD) of the femur (F-BMC, mg and F-BMD, mg/cm(2)) and the fifth lumbar vertebra (V-BMC, mg and V-BMD, mg/cm(2)) were measured separately with dual energy X-ray absorptiometry., Results: The F-BMD, mg/cm(2) was lower in the OVX than in the Sham-OVX group (P<0.0001) and in the other two groups receiving mineral supplements (P<0.005 in both). F-BMC, mg was significantly lower in the OVX group than in the other three (P<0.0001 in all cases). Calculations for V-BMC, mg and V-BMD, mg/cm(2) are similar to findings in the femur., Conclusions: These data show that a Mn supplement is an effective inhibitor of loss of bone mass after OVX, both on the axial and the peripheral levels, although this effect is not enhanced with the addition of Cu.

The effect of silicon (Si) supplement on preventing bone mass loss induced by ovariectomy (OVX) in rats was investigated. Three groups of 15, 100-day-old female Wistar rats each, with a mean initial weight of approximately 260 g per animal, were selected for the present study. One of the experimental group consisting of 15 OVX rats was fed a diet supplemented with 500 mg of Si per kg of feed (Si + OVX). The other two groups consisting of 15 OVX and 15 sham-OVX rats did not receive these supplements. Morphometric (weight and length) and densitometric studies with dual-energy X-ray absorptiometry were performed on the whole femur and 5th lumbar vertebra of each animal 30 days after the experiment. The Si + OVX rats did not show a loss of bone mass induced by OVX at axial level (5th lumbar vertebra) or periphery (femur). Nonetheless, a significant increase (ANOVA with Bonferroni/Dunn post hocs test) of longitudinal development of the femur (P < 0.0001) was patent. These results, obtained through the measurements of axial and peripheral bones, warrant closer scrutiny in connection with the Si inhibitory effect on bone mass loss as well as the stimulatory effect on bone formation. Both actions, namely, inhibition of resorption and stimulation of formation, infer that Si may have a potential therapeutic application in the treatment of involutive osteoporosis.

The effects of salmon calcitonin and clodronate were compared in ovariectomised rats. Sixty female Wistar rats ( 260 g in weight) were fed the same diet and had the same living conditions. The rats were divided into the following groups: 15 rats with sham ovariectomy and no drug treatment (Sham-OVX); 45 rats with bilateral ovariectomy subdivided into 15 rats not receiving drug treatment (OVX group), 15 rats treated with subcutaneous salmon calcitonin, 2 U/kg/day every 2 days (OVX + CT group) and 15 rats treated with subcutaneous clodronate, 5 mg/kg/day every 2 days (OVX + Cl group). Sixty days after surgery, the rats were sacrificed and their femurs and fifth lumbar vertebrae were dissected and cleaned of soft tissue. Femur length, vertebral height, and bone mineral content and bone mineral density of the femur and fifth lumbar vertebra by dual-energy X-ray absorptiometry were measured. Calcitonin had a significant and stronger effect in preventing ovariectomy-induced osteopenia in the femur (OVX + CT vs OVX groups, p < 0.0001); both calcitonin and clodronate had a significant effect on the fifth lumbar vertebra, which was greater in the calcitonin group (OVX + CT vs OVX + Cl groups, p<0.005). These findings indicate that calcitonin has a protective effect on both the axial (trabecular bone) and peripheral (cortical bone) skeletons, but clodronate only has a protective effect on the axial skeleton.

Objective: To report two cases of monozygotic twinning after IVF-blastocyst transfer., Design: Case report., Setting: Private practice in an assisted reproductive technology clinic., Patient(s): Two women treated with IVF-ET at the blastocyst stage., Intervention(s): Pituitary down-regulation with luteal leuprolide acetate, ovulation induction with gonadotropins, IVF, sequential culture, blastocyst transfer, and P for luteal support., Main Outcome Measure(s): Levels of hCG, pelvic ultrasound examination, amniocentesis, obstetric follow-up, and cesarean section., Result(s): Two intrauterine monozygotic twin pregnancies occurred after IVF and blastocyst transfer. One of them was complicated by fetus-to-fetus transfusion syndrome and was delivered preterm by cesarean section; the other woman had a normal pregnancy and vaginal delivery., Conclusion(s): Monozygotic multiple gestations may be increased in IVF blastocyst transfers. The potential obstetric complications of this type of pregnancy should be discussed with patients.

The effect of promethazine on bone is debated. We studied the effect of promethazine on bone and the mechanism of action involved by densitometric and histomorphometric measurements in female Wistar rats (100 days old, mean weight 25 +/- 20 g). A control group of 15 rats was not manipulated. An experimental group of 15 rats were ovariectomized (OVX) at 100 days of life and fed a diet supplemented with 4.8 mg/kg promethazine hydrochloride (OVX + Prom). The group that underwent OVX and a group of 15 rats that underwent sham ovariectomy (Sham-OVX) were not treated with promethazine. After 30 days, all the rats were killed. Their femur and 5th lumbar vertebra were dissected and cleaned of soft tissue. Femoral length and vertebral height were measured with a caliper and bones were weighed on a precision balance. The bone mineral content (BMC) and bone mineral density (BMD) of the whole right femurs and 5th lumbar vertebras were measured by dual-energy X-ray absorptiometry (DXA). Trabecular bone volume (Cn-BV-TV%), trabecular number (Tb-N mm(-1)), trabecular thickness (Tb-Th microm), and trabecular separation (Tb-Sp microm) were measured in the femurs by histomorphometric study of nondecalcified bone. Our results showed that promethazine significantly inhibited postovariectomy loss of bone mass (P < 0. 0001) by significantly reducing bone resorption, as shown by the smaller trabecular spaces observed in the treated OVX rats (P < 0. 0001).

We administered a potassium bicarbonate supplement to rats on strenuous treadmill training in order to determine the effect on bone mass and the metabolic acidosis seen with this type of training. A sample of 45 93-day-old female Wistar rats with a mean initial weight of 267 +/- 17 g were studied. The control group (15 rats) was not exercised or given potassium bicarbonate (Ex- PB-). The experimental group (30 rats) was randomly divided into two subgroups of 15 rats each, one that exercised and did not receive potassium bicarbonate (Ex+ PB-) and one that exercised and received potassium bicarbonate (Ex+ PB+), at a dose of 0.05 mg/kg/day administered by esophageal catheter on exercise days. Training consisted of treadmill running on 5 out of 7 days for a period of 11 weeks. Running time, treadmill speed, and the percent grade were gradually increased until week 7, then maintained until rats were sacrificed at the ened of 11 weeks. The bone mineral content (BMC) and bone mineral density (BMD) of the whole right femur and 5th lumbar vertebra were measured. Femoral and vertebral length were also measured. Femur length, weight, BMC, and BMD, and femur BMC/final weight ratio, and vertebral weight, BMD, and BMC, and vertebral BMC/final weight ratio were lower in the Ex+ PB- group than in either the controls or the Ex+ PB+ group (P < 0.01-P < 0.0001); the length of the 5th lumbar vertebra did not differ between groups.

Rationale and Objectives: The authors determined the effect of obesity on measurements of amplitude-dependent speed of bone ultrasound (Ad-SOS [m/sec]) and compared them to the total body bone mineral content (TBBMC/g)., Methods: A total of 25 women were studied (mean age 41.8 +/- 10.2 years). In all the subjects, body mass index (BMI) exceeded 30 kg/m2 (range, 31.12-47.47 kg/m2); mean body weight was 104 +/- 17 kg. Ad-SOS was measured at the proximal phalanges and TBBMC in whole body with dual-energy x-ray absorptiometry., Results: Correlation study (Fisher's r to z) showed that Ad-SOS correlated negatively with weight (r = -0.85, P < 0.0001) and with TBBMC (r = -0.71, P < 0.0001). The correlation between TBBMC and weight was r = 0.76, P < 0.0001. Body fat percentage correlated partially with TBBMC (r = 0.40, P < 0.05) and negatively with Ad-SOS (r = -0.75, P < 0.0001). When the correlation test was adjusted for weight (partial correlation), the correlation between Ad-SOS and TBBMC was not significant (r = -0.21, P = NS), and the correlation between Ad-SOS and weight continued to be inversely significant (r = -0.67, P < 0.0001)., Conclusions: The results showed a clearly negative effect of weight on Ad-SOS measurements and indicated the limitations of this technique when employed in overweight and obese patients. Broad-band ultrasound attenuation and speed of sound, two commonly measured variables in bone ultrasound studies, may be differently affected by soft tissue.

The ability of alprazolam to diminish cortisol response and favor ovarian function could make it useful in the prevention of osteopenia in athletes in selected cases. A sample of 45 female Wistar rats, all 93 days old and with a mean initial weight of 267 +/- 17 g, were studied. Rats were exposed to a high-performance level of exercise and were divided into two groups-one group received an alprazolam supplement and one did not-and compared with controls to determine the effect of alprazolam on bone mass as measured by dual-energy X-ray absorptiometry (DKA). Exercise consisted of treadmill running on 5 out of 7 days during a period of 11 weeks. A steep grade treadmill inclination was used to stimulate high-intensity muscle activity. Final inclination was 17.5 degrees and treadmill speed was 45 cm/second. Upon completion of the experiment, all the rats were killed and the femur and 5th lumbar vertebra were dissected and cleaned. Length, weight, bone mineral content (BMC), and density (BMD) of the whole right femur and 5th lumbar vertebra were measured. In the exercise only group (no alprazolam), the length, weight, BMC, BMD, and femur BMC/final rat weight ratio of the femur, and the vertebral weight, vertebral BMD and BMC, and vertebral BMC/final rat weight ratio were lower than in the control and the exercise-alprazolam groups (P < 0.0167 - < 0.0001). Alprazolam preserves bone mass in rats exposed to intense exercise.

Objective: To evaluate the effect of surgical uterine retroversion on bone mass in rats., Study Design: Forty-five female Wistar rats were assigned randomly to three groups: 15 unmanipulated rats, 15 rats that underwent uterine retroversion, and 15 rats that underwent sham uterine retroversion (exposure of the uterus to air followed by closure of the abdominal cavity). Sixty days later the rats were killed and their femurs were dissected. Femurs were weighed and measured, and femoral bone mineral content (BMC) and bone mineral density (BMD) were determined by dual energy X-ray absorptiometry., Results: In the group of rats that underwent uterine retroversion, BMC, BMD, and BMC corrected for final body weight were significantly lower (P<0.001) than in the unmanipulated control and sham uterine retroversion groups., Conclusion: Our findings indicate that uterine retroversion induced a loss of bone mass. We could not determine the mechanism of bone loss; in our opinion, these problem merits further investigations, which currently occupy our interest.

Objective: The T score of the cortical and trabecular bone compartments (T score of BMDTrab and T score of BMDCorti) was calculated in healthy postmenopausal women to determine which bone compartment loses more bone mass., Material and Methods: A total 134 healthy postmenopausal women (mean age 55.1 +/- 6.4 years) and 67 healthy premenopausal women (mean age 36.0 +/- 8.6 years) were studied. Determinations were made using peripheral quantitative computed tomography (pQCT) of the nondominant forearm. The postmenopausal women were divided into groups by years since menopause (YSM): two early postmenopausal groups: < 5 YSM and 6-10 YSM; and two late postmenopausal groups: 11-20 YSM and > 20 YSM., Results: There was a significant correlation between the T score of BMDTrab and the T score of BMDCorti (P < 0.0001). Both correlated negatively and significantly with age (P < 0.001 and P < 0.0001, respectively) and neither correlated with weight. The Wilcoxon test showed no significant differences between the trabecular and cortical T scores in the overall group of women. By YSM, only the > 20 YSM group showed significant differences (P < 0.005). The ANOVA post hoc Bonferroni/Dunn test showed a significant difference in the T score of BMDTrab by YSM only in the < 5 YSM versus 11-20 YSM groups (P = 0.007) and in the < 5 YSM versus > 20 YSM groups (P < 0.0001). The T score of BMDCorti by YSM differed significantly only between the < 5 YSM versus 11-20 YSM groups (P < 0.0001) and between the 11-20 YSM and > 20 YSM groups (P < 0.005)., Conclusion: In contrast with what has been postulated in recent studies, our results showed that postmenopausal bone loss was similar in the cortical and trabecular bone compartments in the first 20 years after menopause. Trabecular bone loss was greater than cortical bone loss in late menopause (> 20 years).

Objective: Longitudinal changes in bone mass were evaluated with use of ultrasonography and bone remodeling markers in 40 normal pregnant women in relation to their calcium intake., Study Design: The study took place at the University of Alcalá Hospital in Madrid. Biochemical markers of bone remodeling and ultrasonographic bone propagation velocity in the proximal phalanxes of fingers 2 to 5 were measured in all three trimesters of pregnancy. Wilcoxon, unpaired and paired t tests, and analysis of variance were used., Results: Ultrasonographic bone propagation velocity (meters per second) was lower in the second and third trimesters of pregnancy (p < 0.0001) compared with the respective preceding trimesters and in the third trimester in the overall group of pregnant women. Tartrate-resistant acid phosphatase and alkaline phosphatase levels increased significantly (p < 0.0001) in parallel with the ultrasonographic bone propagation velocity decrease., Conclusions: Gestation was accompanied by a reduction in ultrasonographic bone propagation velocity that was greater in women with low calcium intake.

The hypothesis that a zinc (Zn) deficit may cause osteopenia in athletes is well founded. In rats exposed to strenuous exercise, we evaluated the effect of a zinc supplement on femoral and vertebral bone mass determined by dual-energy X-ray absorptiometry. Four lots of 93-day-old female Wistar rats were studied. A control group of 30 rats were not manipulated (Zn- Ex- group). The experimental group of 40 rats was fed a diet supplemented with an additional 20% of Zn/kg of feed; this group was divided into two groups of 20 rats each, one that did not exercise (Zn+ Ex-) and one that did (Zn+ Ex+). A group of 15 rats exercised but did not receive a zinc supplement (Zn- Ex+ group). Training consisted of treadmill running for 5 out of 7 days over an 11-week period. Initial speed, running time, and treadmill speed were increased gradually. Analysis of variance with the Bonferroni/Dunn test showed that the length, weight, bone mineral content (BMC), and bone mineral density (BMD) of the femur were less in the Zn- Ex+ group than in the others (p < 0.008), and the weight, BMC, and BMD of the fifth lumbar vertebra also were lower in the Zn- Ex+ group than in the others (p < 0.008). These findings confirm the adverse effects of strenuous exercise (treadmill running) on bone tissue in rats and the effectiveness of zinc supplementation in preventing it.

Three techniques of bone mass measurement were evaluated in the diagnosis of postmenopausal osteoporosis; the overlap in the measurements and the capacity for discriminating was determined among 51 postmenopausal normal (mean age 66.6 +/- 8.4 years) and 42 postmenopausal osteoporotic women (mean age 68.5 +/- 7.5 years). All bone mass was evaluated by total body bone mineral content (BMCTB), density (BMDTB), ultrasound bone velocity (UBV) in proximal phalanxes 2-5 of the nondominant hand (UBV = mean value of all ultrasound measurements), and peripheral quantitative computed tomography of the nondominant forearm (pQCT). BMCTB was found to be significantly better (P < 0.0001) for diagnosing postmenopausal osteoporosis than the other methods; both cortical and trabecular pQCT measurements were more discriminating than the corresponding UBV measurements (P < 0.001). T-score values in normals, subjects versus osteoporotic ones were BMCTB -1.15 +/- 0.79 versus -3.17 +/- 0.74; BMDTB -1.01 +/- 0.97 versus -3.28 +/- 0.81; UBV -1.51 +/- 1.02 versus -2.34 +/- 1.21; trabecular-pQCT -0.40 +/- 0.72 versus -1.57 +/- 0.37; cortical-pQCT -1.00 +/- 0.87 versus -2.67 +/- 0.53; and total-pQCT -0.65 +/- 1.01 versus -2.34 +/- 0.27, respectively. The overlap in values between the postmenopausal normal and postmenopausal osteoporotic groups was 50% with UBV, 6% with BMCTB, 9% with BMDTB, 25% with cortical pQCT, and 42% with trabecular pQCT. BMCTB, BMDTB, UBV, and pQCT correlated well with each other as measurements of bone mass, but BMCTB was more discriminating than the other measurements in the diagnosis of osteoporosis.

The influence of body mass index (BMI) on T scores for total body bone mineral content (TBBMC) and regional bone mineral content (RBMC) was studied in 186 healthy women: 100 postmenopausal, 35 perimenopausal, and 51 premenopausal. The three groups were divided by BMI >25 kg/m2 and BMI <25 kg/m2 and the postmenopausal women were further subdivided by years since menopause (YSM): <10, 10-20, and >20. Tartrate-resistant acid phosphatase (TRAP) concentration was higher in perimenopausal and postmenopausal women with BMI <25 kg/m2 (P < 0.001). T scores for TBBMC and for axial or peripheral RBMC differed (P < 0.05 in all) between women with BMI >25 kg/m2 and BMI <25 kg/m2. The rate of perimenopausal and postmenopausal age-related slope of BMC, as reflected in all measurements, differed with BMI. In the overall group of women, the T score for TBBMC correlated significantly with BMI (r = 0.46, P < 0.0001); this correlation increased when adjusted for age (r = 0.62, P < 0.0001). BMI correlated with TRAP only in postmenopausal women (r = 0.57, P < 0. 0001). Yearly TBBMC decline was twice as high in postmenopausal women with BMI <25 kg/m2 (P = 0.0004) than in those with BMI >25 kg/m2; the decline of trunk RBMC was more significant (P < 0.0001). These findings confirm the influence of BMI and gonadal status on bone mass.

Changes in total body bone mineral content (BMCTB) and density (BMDTB), and the T-score of BMCTB and (BMDTB) were evaluated in relation to the number of vertebral fractures in women with postmenopausal osteoporosis for the purpose of defining deviations in these parameters that could be predictive of the occurrence of vertebral fracture. The study group consisted of 62 women diagnosed with postmenopausal osteoporosis. All of them had two or more spinal fractures. Regression analysis of the number of fractures against each parameter studied indicated that the following were predictive of the risk of fracture: a reduction of -0.5 in the T-score of both BMCTB and BMDTB (P < 0.0001) and a loss of about 135 g of BMCTB or 0. 058 g/cm2 of BMDTB (P < 0.0001). The fact that such changes were found during the follow-up of women with osteoporosis highlights the importance of bone mass measurements during follow-up.

The effect of electromagnetic fields on bone is debated. In an experimental study of this effect, we compared two lots of growing female rates (both lots n = 15, age 3 weeks, average weight 23.2 +/- 3.3 g), one of which was exposed to a 3-mT, 100-Hz, Helmholtz-type electromagnetic field for 24 hours a day for 30 days, and the other of which served as the control. Bone development and bone mass were evaluated by morphometry, densitometry, and histomorphometry. The rats were killed at 30 days and weighed. The right femurs were dissected, measured, and weighed; bone densitometry was used to determine femoral bone mineral content (BMC) and density (BMD), and histomorphometry of the nondecalcified bone was used to determine trabecular bone volume (Cn-BV-TV%), number (Tb-N mm) and thickness (Tb-Th microm), intertrabecular space (Tb-Sp microm) and growth cartilage thickness (Gc-Th microm). In the rats exposed to the electromagnetic field, BMC and BMD (P = 0.019 and P = 0.002, respectively) and Cn-BV-TV, Tb-N, Tb-Th (P = 0.005, P = 0.036, and P = 0.027, respectively) all were decreased, whereas Tb-Sp was increased (P = 0.002). There were no significant differences in initial and final body weight, or in final femur weight, femur length, and GC-Th. These findings indicate that electromagnetic fields of the type used here reduced bone formation and increased bone resorption without affecting bone development in rats.

Eighty-one women were studied longitudinally to measure trabecular bone mineral density (BMDTrab) and cortical bone mineral density (BMDCorti) in the distal radius by peripheral quantitative computed tomography (pQCT) at intervals of about 1 year and to calculate the rate of percent change/year. Fifty-three women were naturally postmenopausal [mean age 63.3 +/- 5.3 years, age at menopause 50.7 +/- 3.8 years, 13 years since menopause (YSM)] and 28 had been ovariectomized (mean age 52.7 +/- 5.8 years, age at menopause 39.5 +/- 5.0 years, 13 YSM). There was no difference between groups (ANOVA) in the rate of percent change/years in BMDTrab (p = 0.692), but there was in BMDCorti (p = 0.020). When the women who had either gained or lost bone mass were compared (chi-square test), only BMDCorti differed significantly (p = 0.018). Considering > -2.5% change/years as the limit for rapid bone mass loss, BMDTrab values showed that 43% of the naturally postmenopausal women and 42.7% of the ovariectomized women had rapid bone loss (p ns). On the basis of BMDCorti values, 45% of the naturally postmenopausal women and 28.4% of the ovariectomized women had rapid bone loss (p = 0.018). Height, weight, body mass index (BMI), age, YSM, and years of reproductive life did not differ (ANOVA) between the women who gained or lost either BMDTrab or BMDCorti. Using Fisher's r to z and partial correlation adjusted for age and YSM of the percent change/year in BMDTrab and BMDCorti in the overall group and in each menopausal group, only BMDCorti differed.

The effect of exposure to lead on the longitudinal development of bone and on bone mass was studied in rats. A group of 35, 50-day-old female Wistar rats was divided into a control group of 15 rats and an experimental group of 20 rats fed a diet supplemented with 17 mg of lead acetate per kg feed for 50 days. Total body bone densitometry (TBBMC) was performed the day before ending the 50-day experiment. On day 50, all rats were killed and their right femur and 5th lumbar vertebra were dissected. The bones were cleaned of soft tissue and femoral length and vertebral length were measured with a caliper and all bones were weighed on a precision scale. Final body weight (P < 0.05), TBBMC (P < 0.005), and femur weight (P < 0.005) were significantly lower in the control group. Femur length did not differ between groups, but the length of the 5th lumbar vertebra was greater in the control group (P < 0.05). Histomorphometry of the femur showed that Cn-BV/TV, Tb-N, Tb-Th were lower (P < 0.05 in all) and Tb-Sp was higher (P < 0.05) in the group given the lead-supplemented diet. These findings suggested lead-induced inhibition of axial bone development and a histomorphometric decrease in bone mass, produced mainly by enhanced resorption, and a densitometric increase in bone mass, produced by lead accumulation in bone.

The effect of exposure to lead on the longitudinal development of the femur and of its cartilage growth plate was studied in rats. A group of forty-five 50-day-old female Wistar rats was divided into a control group of 20 rats and an experimental group of 25 rats fed a diet supplemented with 17 mg of lead acetate per kilogram of feed for 50 days. On Day 50 all rats were killed and their right femurs were dissected. The femurs were cleaned of soft tissue and femoral lengths were measured with a Vernier caliper and thickness of growth cartilage (GPC-Th micron) by histomorphometry. Final body weights were significantly (P < 0.05) lower in the control group than in the rats given the lead-supplemented diet. Femur length did not differ between groups. Histomorphometry of the femur showed that the thickness of growth cartilage was higher (P < 0.05) in the control group. These findings suggested lead-induced inhibition of growth plate development. The growth plate may be one of the key target tissues accounting for the adverse effects of chronic lead exposure on skeletal development.

Rationale and Objectives: The authors studied premenopausal, perimenopausal, and postmenopausal women to determine if ultrasound bone velocity (UBV) on proximal phalanges of women reflect bone changes related to gonadal status and age., Methods: A total of 166 healthy women-64 postmenopausal women (mean age 58.7 +/- 9.4 years), 41 perimenopausal women (mean age 49.5 +/- 2.9 years), and 61 premenopausal women (mean age 36.8 +/- 7.1 years)-were studied. All the women underwent UBV study of the 2nd to 5th proximal phalanges on the nondominant hand and the mean value of all ultrasound measurements was calculated., Results: The postmenopausal women had a UBV that differed significantly, one-way analysis of variance, from that of the perimenopausal women and premenopausal women (both P < 0.001). The UBV measurements of the perimenopausal women differed significantly from those of the premenopausal women (P < 0.01). Simple linear regression analysis of the relation between UBV and age showed that this was significant and negative in the overall group of women (r = -0.69; P < 0.0001), significant in the perimenopausal (r = -0.66; P < 0.001) and postmenopausal women (r = -0.69; P < 0.001) and nonsignificant in the premenopausal women (r = 0.08; P not significant). In the postmenopausal women, the correlation between UBV and years since menopause was larger (r = -0.71; P < 0.0001) than the correlation between UBV and chronological age., Conclusions: Ultrasound bone velocity of the phalanx, as a method for measuring changes in bone with age, has a precision that makes it possible to detect changes in bone mass in perimenopausal women and may perform similarly to other bone mass measurements.

In experimental studies of bone in rats, two morphometric indices reflecting bone density have been proposed, the bone robusticity index and bone weight/bone length index. In rats, the bone mineral content (BMC) and bone mineral density (BMD) of a selected bone can be determined using dual-energy X-ray absorptiometry (DXA); bone volume can be measured by histomorphometry and other techniques. This study was undertaken to compare two morphometric indices (bone robusticity and bone weight/bone length) with the results of DXA and histomorphometry. Forty female Wistar rats (100 days old, mean weight 239+/-12 g) were studied: 20 controls and 20 ovariectomized rats (OVX). The morphometric indices and BMD differed significantly (Friedman test) in the overall group of rats; no differences were observed in the control group, but significant differences were apparent in the OVX group (p<0.0001). The morphometric indices correlated more closely with BMC than with BMD; the femur length/ femur weight index had closer correlations than the robusticity index. Nonetheless, both morphometric indices differed significantly from BMD determined by DXA under abnormal conditions, which makes them unreliable for use in these circumstances.

Since Ras proteins are essential intermediates of some insulin-like growth factor I (IGF-I)/insulin signaling pathways, we examined whether Ras proteins mediate the IGF-I-induced uncoupling protein expression. Additionally, the role of Ras proteins on IGF-I and IGF-I receptor expression was studied. IGF-I treatment of fetal brown adipocytes cotransfected with inducible gene constructs of SV40 large T antigen (SV40LTag) and a transforming ras gene induced uncoupling protein expression (UCP) in the absence of expression of the transfected genes. The expression of the dexamethasone-inducible transforming ras gene alone or in combination with the Zn-inducible SV40LTag mimicked the IGF-I effect inducing UCP expression and IGF-I did not induce it further. However, the expression of the Zn-inducible SV40LTag did not increase UCP expression in the absence of IGF-I. Expression of the transfected ras oncogene also induced IGF-I and IGF-I receptor mRNAs, whereas expression of SV40LTag did not increase them. Specific IGF-I binding was also specifically increased by expression of the transfected ras oncogene but was not affected by expression of the SV40LTag construct. These results indicate that Ras proteins mediate the IGF-I-induced effect on UCP expression and play a role in the expression of IGF-I and IGF-I receptor. Therefore, an IGF-I autocrine/paracrine loop might be implicated in the process of thermogenic differentiation of brown adipose tissue by a new mechanism unlike that induced by norepinephrine.

Having observed that serum beta(2)-microglobulin concentration correlates with serum tartrate-resistant acid phosphatase (TRAP) concentration in postmenopausal osteoporosis, and that metacarpal endosteal diameter is dependent on bone resorption, we correlated the two biochemical parameters with the radiographic parameter to determine if beta(2)-microglobulin behaves like a biological marker of bone remodelling. In 105 women (mean age 68 +/- 4 years) consisting of 60 normal postmenopausal women and 55 osteoporotic postmenopausal women, there was a significant positive correlation between metacarpal endosteal diameter and these two biochemical values (r = 0.66 with beta(2)-microglobulin and r = 0.68 with TRAP in the osteoporotic postmenopausal women; r = 0.48 with beta(2)-microglobulin and r = 0.56 with TRAP in the normal postmenopausal women; P < 0.001 for all comparisons). All three measurements were significantly higher (P < 0.001) in the osteoporotic postmenopausal women than in the normal postmenopausal women. These findings show that serum beta(2)-microglobulin behaves like a biological marker of remodelling.