Treatment with alendronate prevents fractures in women at highest risk: results from the Fracture Intervention Trial

BACKGROUND: The efficacy of antiresorptive therapy in preventing fractures in women at highest fracture risk, such as very elderly women or those with severe osteoporosis, is uncertain. PARTICIPANTS AND METHODS: Using data from a double-blind, randomized, placebo-controlled clinical trial that enrolled 2027 postmenopausal women aged 55 to 81 years with low femoral neck bone mineral density (BMD) and existing vertebral fractures, we examined the consistency of the effect of treatment with alendronate sodium in preventing fractures within a priori-specified risk subgroups defined at baseline by age, bone density, number of preexisting vertebral fractures, and history of postmenopausal fracture. The women were randomized to oral administration of alendronate or placebo and followed up for an average of 2.9 years. The initial dose of alendronate sodium was 5 mg/d; the dosage was increased from 5 to 10 mg/d at 24 months. New vertebral fractures, the primary end point of this arm of the trial, were defined by morphometry as a decrease of 20% and at least 4 mm in any vertebral height between baseline and a follow-up radiograph at 36 months. Incident clinical fractures, the secondary end point, included nonspine and clinical (symptomatic) vertebral fractures. All clinical fractures were confirmed with x-ray film reports or, in the case of clinical vertebral fractures, x-ray films. RESULTS: Overall, there was a 47% significant reduction in risk of new vertebral fractures in the alendronate group compared with the placebo group. The reduction in risk of new vertebral fracture was consistent across fracture risk categories including age (relative risk [RR], 0.49 in women < 75 years compared with 0.62 in those > or = 75 years), BMD (RR, 0.54 in women with a femoral neck BMD < 0.59 g/cm2 [median] compared with 0.53 in those with a BMD > or = 0.59 g/cm2), and number of preexisting vertebral fractures (RR, 0.58 in women with 1 vertebral fracture compared with 0.52 in those with > or = 2). The overall significant 28% reduction in risk of incident clinical fractures in the alendronate group compared with the placebo group was also observed within these subgroups. Compared with the number of lower-risk women, a similar or smaller number of high-risk women needed to be treated to prevent 1 fracture. For example, 8 women aged 75 years or older compared with 9 women younger than 75 years, or 4 women with 2 or more existing vertebral fractures compared with 16 women with 1 existing vertebral fracture, needed to be treated with alendronate for 5 years to prevent 1 new vertebral fracture. CONCLUSIONS: Alendronate effectively reduces fracture risk in postmenopausal women with vertebral fractures and low BMD, including those women at highest risk because of advanced age or severe osteoporosis. Since the risk reductions observed with alendronate treatment were consistent within fracture risk categories, more fractures were prevented by treating women at highest risk.     

Neutral endopeptidase inhibition increases the potency of ANP in isolated rat pulmonary resistance vessels and isolated blood perfused lungs

We have investigated the effects of the neutral endopeptidase inhibitor, SCH 42354, on the vasoreactivity of atrial natriuretic peptide (ANP) in rat isolated pulmonary resistance vessels (PRV) and isolated perfused lungs (IPL). PRV (n = 37) were mounted onto the jaws of a myograph and precontracted with PGF2alpha (100 mu M). Concentration-responses to ANP (0.17 to 340 nM) were determined before and after the addition of SCH 42354 (10, 30 and 100 nM). Each concentration of SCH 42354 caused a significant increase in potency (- log EC50) of ANP in isolated PRV. Lungs from normoxic rats (n = 13) were isolated and perfused with whole blood. An increase in pulmonary artery pressure was achieved by ventilating with an hypoxic gas mixture and concentration-responses obtained by incremental additions of ANP (40 nM to 12 mu M), before and after the addition of SCH 42354 (100 nM). SCH 42354 significantly increased the potency (- log EC50) of ANP in the rat IPL. ANP is partly metabolized by NEP. That an inhibitor of NEP increased the potency of ANP in isolated pulmonary vessels, and in isolated perfused whole lungs, suggested that SCH 42354 may be having a local action within the pulmonary vasculature.     

Effect of Feathery Mottle Virus Infection on Sweet Potato Sensory Properties

Four sets of sweet potato clones obtained by meristem tip culture were used to investigate the effect of feathery mottle virus (FMV) infection on the appearance, sensory quality and chemical composition of the storage roots. This study, encompassing four generations, indicated that FMV infection had a slight effect on carbohydrate metabolism but no effect on the polyphenoloxidase-phenol system. Flavor and texture profile analyses indicated that for one clone, FMV-infected roots were more desirable when baked than healthy roots. Considering the study as a whole, FMV infection did not appear to adversely affect sweet potato sensory properties. Clones produced from the same parent by meristem tip culture might have different compositional and sensory properties.     

Effects of amount of whole cottonseed on intake, digestibility, and physiological responses of dairy cows

In Experiment 1, 27 lactating cows were fed complete rations ad libitum of 0, 15, and 30% whole cottonseed to examine the effects on intake, digestibility, blood gases, and blood metabolites. Dry matter intake declined linearly with increased cottonseed, but because of greater energy density, calculated net energy for lactation intake was not depressed significantly. Ether extract, crude protein, and calcium digestibility increased with cottonseed in the diet. Respiration rates declined with dry matter intake and increased cottonseed feeding; some blood gases were influenced by cottonseed feeding but not in a detrimental way. No data among 13 blood metabolites indicated effects of gossypol toxicity with 30% whole cottonseed in the diet. In Experiment 2, 24 dry, nonpregnant Holstein cows were offered complete rations ad libitum of 15, 35, and 55% whole cottonseed to measure responses in intake, respiration rates, and blood metabolites. The highest cottonseed diet significantly depressed intake of both dry matter and calculated net energy for lactation. Maximum dry matter from cottonseed eaten by an individual was 8.4 kg/d (average for 1 wk). Respiration rates declined parallel to intake. No evidence for gossypol toxicity was seen among data of 11 metabolites in blood.     

Downward comparison, prejudice, and evaluations of others: Effects of self-esteem and threat.

In two studies, we explored the effects of trait self-esteem and threats to the self-concept on evaluations of others. In Study 1, subjects high, moderate, and low in self-esteem received either success, failure, or no feedback on a test and later evaluated three pairs of targets: ingroups and outgroups based on a minimal intergroup manipulation, those who scored above average and those who scored below average on the test, and themselves and the average college student. Study 2 explored the effects of self-esteem and threat on ingroup favoritism in a real-world setting, campus sororities. Together, the results of these studies indicate that individuals high in self-esteem, but not those low in self-esteem, respond to threats to the self-concept by derogating outgroups relative to the ingroup when the group boundaries have evaluative implications. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Characterization of a lectin-like protein isolated from Lachesis muta snake venom

A lectin-like protein was isolated from L. muta venom by gel filtration on BIO Gel P-100 followed by column Chromatography on DEAE-sephades A-50. The protein eluted at 0.4 M Nacl in 0.01 Tris pH 7.3 and exhibited agglutinin activity toward 0+ human erythrocytes. The protein is a dimer with Mr 28 kDa. Amino acid analysis revealed high content of tryptophan and acid recidues and low content of cysteine and methionine residues. No neutral carbohydrates and sialic acid were detected. Circular dichroic spectrum shows 78% of B structure and 1% of alpha structure. In vitro experiments with erythrocytes from rat, rabbit and dog revealed strong agglutination while red blood cells from mice, sheep and goat were not agglutinated. In vivo experiments using anesthetized rats, a sharp and prolonged fall in the blood pressure was observed at protein dose of 1.5 mg/kg. Double dose of protein caused the death of the animal.     

The design of robots and intelligent manipulators using modern composite materials

The operating speed and endpoint positional accuracy of existing industrial manipulators are limited by the inertial and stiffness characteristics of the articulating members of the robot's mechanical linkage. This limitation may be overcome by developing members having high structural stiffness and strength with low mass, and this has been recognized for some time. These characteristics can be obtained by fabricating the moving members of manipulators in fiber reinforced composite materials. In order to establish a basis for the dynamic analysis of robots fabricated in viscoelastic composites, a variational theorem is developed herein. A preliminary comparative study is then undertaken for manipulators manufactured in a graphite-epoxy composite material and also steel in order to demonstrate some of the advantages to be accrued from this proposed new design philosophy.     

Distal dorsal forearm flap

Reinstatement and spontaneous recovery of previously extinguished nicotine-taking behavior were examined in rats. Male subjects were trained to self-administer nicotine (30 microg/kg per infusion, IV; one 60-min session per day for 3 weeks). Extinction sessions were then given for 5-10 days during which saline was substituted for nicotine. Subsequently, in the first set of tests for nicotine seeking, the reinstatement of lever presses that previously delivered nicotine was examined after priming injections of saline and nicotine (75, 150 and 300 microg/kg, SC; and 30 and 60 microg/kg, IV). In the second set of tests for nicotine-seeking, rats were tested after an additional 21-day drug-free period during which they were not exposed to the self-administration chambers (a test for the spontaneous recovery of drug seeking), and after priming injections of nicotine (150 and 300 microg/kg, SC). Reinstatement of extinguished food-reinforced behavior after exposure to nicotine was also determined. Priming injections of nicotine reinstated nicotine seeking regardless of the route of administration. In addition, previously extinguished nicotine seeking recovered spontaneously after a 21-day period during which rats were not exposed to the drug-taking environment. Nicotine also reinstated extinguished food-reinforced behavior in rats with a history of nicotine self-administration, but not in drug-naive rats. The present results extend previous work with opioid and stimulant drugs on reinstatement of drug seeking by the self-administered drug. It also appears that, as with other positive reinforcers, the mere passage of time is a sufficient condition for the spontaneous recovery of extinguished nicotine seeking.     

Tolerance of volunteers to cyclosporine A-dilauroylphosphatidylcholine liposome aerosol

Cyclosporine A (CsA) in liposomes of dilauroylphosphatidylcholine (DLPC), containing 118 micrograms of CsA/L of aerosol with a particle size of 1.6 to 1.7 micron diameter, was inhaled by 10 nonsmoking, normal volunteers each for 45 min. Aerosol was administered through an Aerotech II nebulizer (CIS-US, Inc., Bedford, MA) mouthpiece. Eight of the 10 volunteers had tracheal irritation and intermittent coughing following exposure. FEV1 and FVC values were mildly reduced, but returned to normal in 1 h. Blood chemical and hematologic values were unchanged at any time point after as opposed to before inhalation. Nine of the 10 volunteers later inhaled DLPC only, administered through the nebulizer mouthpiece. There was no change in FEV1 or FVC values, and there was no coughing or tracheal irritation. Subsequently, five of the volunteers who had previously had respiratory reactions inhaled CsA-DLPC liposome aerosol for 45-min, but through a mouth-only face mask. There was no tracheal irritation, coughing, or changes in spirometric measures. Blood concentrations of CsA at 15 min after the 45-min inhalation with a face mask averaged 83 +/- 42 ng/ml (mean +/- SD). At 24 h after treatment, CsA was undetectable in blood of the initial 10 volunteers. These studies indicate that CsA-DLPC liposome aerosol can be safely explored as a treatment for patients with moderately severe asthma.