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1.
Science ; 373(6551): 198-204, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244410

RESUMO

Mars' sedimentary rock record preserves information on geological (and potential astrobiological) processes that occurred on the planet billions of years ago. The Curiosity rover is exploring the lower reaches of Mount Sharp, in Gale crater on Mars. A traverse from Vera Rubin ridge to Glen Torridon has allowed Curiosity to examine a lateral transect of rock strata laid down in a martian lake ~3.5 billion years ago. We report spatial differences in the mineralogy of time-equivalent sedimentary rocks <400 meters apart. These differences indicate localized infiltration of silica-poor brines, generated during deposition of overlying magnesium sulfate-bearing strata. We propose that destabilization of silicate minerals driven by silica-poor brines (rarely observed on Earth) was widespread on ancient Mars, because sulfate deposits are globally distributed.

2.
J Geophys Res Planets ; 125(8): e2019JE006295, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32999799

RESUMO

The Curiosity rover's exploration of rocks and soils in Gale crater has provided diverse geochemical and mineralogical data sets, underscoring the complex geological history of the region. We report the crystalline, clay mineral, and amorphous phase distributions of four Gale crater rocks from an 80-m stratigraphic interval. The mineralogy of the four samples is strongly influenced by aqueous alteration processes, including variations in water chemistries, redox, pH, and temperature. Localized hydrothermal events are evidenced by gray hematite and maturation of amorphous SiO2 to opal-CT. Low-temperature diagenetic events are associated with fluctuating lake levels, evaporative events, and groundwater infiltration. Among all mudstones analyzed in Gale crater, the diversity in diagenetic processes is primarily captured by the mineralogy and X-ray amorphous chemistry of the drilled rocks. Variations indicate a transition from magnetite to hematite and an increase in matrix-associated sulfates suggesting intensifying influence from oxic, diagenetic fluids upsection. Furthermore, diagenetic fluid pathways are shown to be strongly affected by unconformities and sedimentary transitions, as evidenced by the intensity of alteration inferred from the mineralogy of sediments sampled adjacent to stratigraphic contacts.

3.
J Muscle Res Cell Motil ; 38(2): 201-214, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28634643

RESUMO

Caffeine is a highly catabolic dietary stimulant. High caffeine concentrations (1-10 mM) have previously been shown to inhibit protein synthesis and increase protein degradation in various mammalian cell lines. The purpose of this study was to examine the effect of short-term caffeine exposure on cell signaling pathways that regulate protein metabolism in mammalian skeletal muscle cells. Fully differentiated C2C12 skeletal myotubes either received vehicle (DMSO) or 5 mM caffeine for 6 h. Our analysis revealed that caffeine promoted a 40% increase in autolysosome formation and a 25% increase in autophagic flux. In contrast, caffeine treatment did not significantly increase the expression of the skeletal muscle specific ubiquitin ligases MAFbx and MuRF1 or 20S proteasome activity. Caffeine treatment significantly reduced mTORC1 signaling, total protein synthesis and myotube diameter in a CaMKKß/AMPK-dependent manner. Further, caffeine promoted a CaMKII-dependent increase in myostatin mRNA expression that did not significantly contribute to the caffeine-dependent reduction in protein synthesis. Our results indicate that short-term caffeine exposure significantly reduced skeletal myotube diameter by increasing autophagic flux and promoting a CaMKKß/AMPK-dependent reduction in protein synthesis.


Assuntos
Autofagia/efeitos dos fármacos , Cafeína/efeitos adversos , Fibras Musculares Esqueléticas/metabolismo , Proteínas Musculares/efeitos dos fármacos , Músculo Esquelético/metabolismo , Biossíntese de Proteínas/efeitos dos fármacos , Humanos , Proteínas Musculares/metabolismo
4.
J Geophys Res Planets ; 122(12): 2510-2543, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29497589

RESUMO

The Mars Science Laboratory Curiosity rover performed coordinated measurements to examine the textures and compositions of aeolian sands in the active Bagnold dune field. The Bagnold sands are rounded to subrounded, very fine to medium sized (~45-500 µm) with ≥6 distinct grain colors. In contrast to sands examined by Curiosity in a dust-covered, inactive bedform called Rocknest and soils at other landing sites, Bagnold sands are darker, less red, better sorted, have fewer silt-sized or smaller grains, and show no evidence for cohesion. Nevertheless, Bagnold mineralogy and Rocknest mineralogy are similar with plagioclase, olivine, and pyroxenes in similar proportions comprising >90% of crystalline phases, along with a substantial amorphous component (35% ± 15%). Yet Bagnold and Rocknest bulk chemistry differ. Bagnold sands are Si enriched relative to other soils at Gale crater, and H2O, S, and Cl are lower relative to all previously measured Martian soils and most Gale crater rocks. Mg, Ni, Fe, and Mn are enriched in the coarse-sieved fraction of Bagnold sands, corroborated by visible/near-infrared spectra that suggest enrichment of olivine. Collectively, patterns in major element chemistry and volatile release data indicate two distinctive volatile reservoirs in Martian soils: (1) amorphous components in the sand-sized fraction (represented by Bagnold) that are Si-enriched, hydroxylated alteration products and/or H2O- or OH-bearing impact or volcanic glasses and (2) amorphous components in the fine fraction (<40 µm; represented by Rocknest and other bright soils) that are Fe, S, and Cl enriched with low Si and adsorbed and structural H2O.

5.
Am J Surg ; 213(3): 534-538, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27863718

RESUMO

BACKGROUND: The impact of immediate breast reconstruction on the time to first adjuvant therapy is controversial. METHODS: Retrospective study design comparing time to first treatment in women undergoing mastectomy with and without immediate reconstruction in a community cancer center. RESULTS: Seventy-six cases fit inclusion criteria of which 44 (58%) underwent mastectomy with immediate reconstruction. Women undergoing immediate reconstruction were younger, had more bilateral mastectomies and had fewer prior breast procedures. The median time to first adjuvant therapy was longer in the immediate reconstruction group [80.5days (36-343) versus 53.5 days (18-96), p = 0.003]. Fifteen of 44 patients had the start of adjuvant treatment over 90 days after resection, 14 of whom (93%) had immediate reconstruction versus 1 (7%) who did not (p = 0.01). CONCLUSION: In this study immediate breast reconstruction was associated with a longer time to first adjuvant treatment, with adjuvant therapies being more likely delayed over 90 days.


Assuntos
Neoplasias da Mama/terapia , Mamoplastia , Mastectomia , Tempo para o Tratamento , Fatores Etários , Institutos de Câncer , Quimioterapia Adjuvante , Centros Comunitários de Saúde , Feminino , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Radioterapia Adjuvante , Estudos Retrospectivos
6.
Biochem Biophys Res Commun ; 480(1): 61-68, 2016 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-27717822

RESUMO

Caffeine is a widely consumed stimulant that has previously been shown to promote cytotoxic stress and even cell death in numerous mammalian cell lines. Thus far there is little information available regarding the toxicity of caffeine in skeletal muscle cells. Our preliminary data revealed that treating C2C12 myotubes with 5 mM caffeine for 6 h increased nuclear fragmentation and reduced basal and maximal oxygen consumption rate (OCR) in skeletal myotubes. The purpose of this study was to further elucidate the pathways by which caffeine increased cell death and reduced mitochondrial respiration. We specifically examined the role of c-Jun N-terminal kinase (JNK), which has previously been shown to simultaneously increase caspase-dependent cell death and reduce mitochondrial respiration in other mammalian cell lines. We found that caffeine promoted a dose-dependent increase in cell death in multinucleated myotubes but did not in mononucleated myoblasts. The addition of 10 µM Z-DEVD-FMK, a specific inhibitor of executioner caspases, completely inhibited caffeine-dependent cell death. Further, the addition of 400 µM dantrolene, a specific ryanodine receptor (RYR) inhibitor, prevented the caffeine-dependent increase in cell death and the reduction in basal and maximal OCR. We also discovered that caffeine treatment significantly increased the phosphorylation of JNK and that the addition of 30 µM SP600125 (JNKi), a specific JNK inhibitor, partially attenuated caffeine-induced cell death without preventing the caffeine-dependent reduction in basal and maximal OCR. Our results suggest that JNK partially mediates the increase in caspase-dependent cell death but does not contribute to reduced mitochondrial respiration in caffeine-treated skeletal muscle cells. We conclude that caffeine increased cell death and reduced mitochondrial respiration in a calcium-dependent manner by activating the RYR and promoting reticular calcium release.


Assuntos
Cafeína/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Mitocôndrias/efeitos dos fármacos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Animais , Antracenos/farmacologia , Cafeína/toxicidade , Caspase 3/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular , Dantroleno/farmacologia , Relação Dose-Resposta a Droga , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Camundongos , Mitocôndrias/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Inibidores de Proteínas Quinases/farmacologia
7.
Express Polym Lett ; 10(5): 430-437, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-32206095

RESUMO

In this study, electrospun polycaprolactone (PCL) fibers are plasma-treated and chemically conjugated with cholesteryl succinyl silane (CSS). In addition to Raman spectroscopy, an immobilization study of DiO as a fluorescent probe of lipid membranes provides evidence supporting the CSS coating of plasma-treated PCL fibers. Further, anti-CD20 antibodies are used as a model protein to evaluate the potential of lipid-mediated protein immobilization as a mechanism to functionalize the CSS-PCL fiber scaffolds. Upon anti-CD20 functionalization, the CSS-PCL fiber scaffolds capture Granta-22 cells 2.4 times more than the PCL control does, although the two fiber scaffolds immobilize a comparable amount of anti-CD20. Taken together, results from the present study demonstrate that the CSS coating and CSS-mediated antibody immobilization offers an appealing strategy to functionalize electrospun synthetic polymer fibers and confer cell-specific functions on the fiber scaffolds, which can be mechanically robust but often lack biological functions.

8.
Osteoporos Int ; 26(8): 2175-84, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25876880

RESUMO

UNLABELLED: Calcium use was common and remained high among women on osteoporosis therapy. Use of calcium-supplemented pharmacologic therapy increased from 65.1 to 76.0% in these women (mean follow-up, 27.5 months). Over 12 months, calcium discontinuation was fairly similar among women using calcium only (23.7%) and women supplementing pharmacologic therapy with calcium (22.5%). INTRODUCTION: Calcium has an important role in bone health. This study describes calcium use and persistence in a postmenopausal osteoporosis treatment cohort. METHODS: Subject-reported calcium use was analyzed for 3,722 participants of the Prospective Observational Scientific Study Investigating Bone Loss Experience (POSSIBLE US(TM)) who used calcium either as their sole osteoporosis treatment (calcium only) or to supplement pharmacologic osteoporosis therapy (supplementers). Descriptive analyses were conducted. Kaplan-Meier methods were used to estimate the probability of discontinuing calcium therapy, and logistic regression was used to assess associations (age-adjusted odds ratios) between healthy behaviors and calcium use. RESULTS: At entry, there were 711 calcium-only subjects and 1,960 of 3,011 subjects on pharmacologic osteoporosis therapy also supplementing with calcium (supplementers). The percentage of supplementers increased from 65.1 to 76.0% during follow-up (mean, 27.5 months). During the first 12 months on study, the probability of calcium discontinuation was 23.7% (95 % confidence interval [CI], 20.7 - 27.0) among calcium-only subjects and 22.5% (95% CI, 20.7-24.5) among supplementers. Supplementers who discontinued pharmacologic therapy were more likely to discontinue calcium than supplementers who continued pharmacologic therapy (34.9 versus 14.8%). Overall 54.2% of calcium-only subjects who discontinued calcium and 42.3% of supplementers who discontinued calcium resumed calcium use during follow-up. Regular exercise was positively correlated with calcium use at study entry. CONCLUSIONS: Calcium supplementation in pharmacologically treated subjects increased over time. Persistence with calcium was high. Discontinuation of pharmacologic osteoporosis therapy was associated with an increased likelihood of discontinuing calcium use.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Cálcio/administração & dosagem , Osteoporose Pós-Menopausa/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Cálcio/uso terapêutico , Estudos de Coortes , Suplementos Nutricionais , Quimioterapia Combinada , Uso de Medicamentos/estatística & dados numéricos , Feminino , Seguimentos , Comportamentos Relacionados com a Saúde , Humanos , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Autorrelato
9.
IUCrJ ; 1(Pt 6): 514-22, 2014 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-25485131

RESUMO

The Mars Science Laboratory landed in Gale crater on Mars in August 2012, and the Curiosity rover then began field studies on its drive toward Mount Sharp, a central peak made of ancient sediments. CheMin is one of ten instruments on or inside the rover, all designed to provide detailed information on the rocks, soils and atmosphere in this region. CheMin is a miniaturized X-ray diffraction/X-ray fluorescence (XRD/XRF) instrument that uses transmission geometry with an energy-discriminating CCD detector. CheMin uses onboard standards for XRD and XRF calibration, and beryl:quartz mixtures constitute the primary XRD standards. Four samples have been analysed by CheMin, namely a soil sample, two samples drilled from mudstones and a sample drilled from a sandstone. Rietveld and full-pattern analysis of the XRD data reveal a complex mineralogy, with contributions from parent igneous rocks, amorphous components and several minerals relating to aqueous alteration. In particular, the mudstone samples all contain one or more phyllosilicates consistent with alteration in liquid water. In addition to quantitative mineralogy, Rietveld refinements also provide unit-cell parameters for the major phases, which can be used to infer the chemical compositions of individual minerals and, by difference, the composition of the amorphous component.

10.
Biochem Biophys Res Commun ; 453(3): 411-8, 2014 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-25268764

RESUMO

Caffeine has been shown to promote calcium-dependent activation of AMP-activated protein kinase (AMPK) and AMPK-dependent glucose and fatty acid uptake in mammalian skeletal muscle. Though caffeine has been shown to promote autophagy in various mammalian cell lines it is unclear if caffeine-induced autophagy is related to the calcium-dependent activation of AMPK. The purpose of this study was to examine the role of calcium-dependent AMPK activation in regulating caffeine-induced autophagy in mammalian skeletal muscle cells. We discovered that the addition of the AMPK inhibitor Compound C could significantly reduce the expression of the autophagy marker microtubule-associated protein 1 light chain 3b-II (LC3b-II) and autophagic vesicle accumulation in caffeine treated skeletal muscle cells. Additional experiments using pharmacological inhibitors and RNA interference (RNAi) demonstrated that the calcium/calmodulin-activated protein kinases CaMKKß and CaMKII contributed to the AMPK-dependent expression of LC3b-II and autophagic vesicle accumulation in a caffeine dose-dependent manner. Our results indicate that in skeletal muscle cells caffeine increases autophagy by promoting the calcium-dependent activation of AMPK.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia/efeitos dos fármacos , Cafeína/farmacologia , Cálcio/metabolismo , Músculo Esquelético/efeitos dos fármacos , Animais , Linhagem Celular , Ativação Enzimática , Camundongos , Músculo Esquelético/citologia , Músculo Esquelético/enzimologia
11.
Science ; 343(6169): 1243480, 2014 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-24324271

RESUMO

Sedimentary rocks at Yellowknife Bay (Gale crater) on Mars include mudstone sampled by the Curiosity rover. The samples, John Klein and Cumberland, contain detrital basaltic minerals, calcium sulfates, iron oxide or hydroxides, iron sulfides, amorphous material, and trioctahedral smectites. The John Klein smectite has basal spacing of ~10 angstroms, indicating little interlayer hydration. The Cumberland smectite has basal spacing at both ~13.2 and ~10 angstroms. The larger spacing suggests a partially chloritized interlayer or interlayer magnesium or calcium facilitating H2O retention. Basaltic minerals in the mudstone are similar to those in nearby eolian deposits. However, the mudstone has far less Fe-forsterite, possibly lost with formation of smectite plus magnetite. Late Noachian/Early Hesperian or younger age indicates that clay mineral formation on Mars extended beyond Noachian time.


Assuntos
Meio Ambiente Extraterreno/química , Sedimentos Geológicos/química , Marte , Minerais/química , Óxido Ferroso-Férrico/análise , Óxido Ferroso-Férrico/química , Sedimentos Geológicos/análise , Minerais/análise , Silicatos/análise , Silicatos/química , Compostos de Silício/análise , Compostos de Silício/química
12.
Science ; 341(6153): 1238932, 2013 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-24072925

RESUMO

The Mars Science Laboratory rover Curiosity scooped samples of soil from the Rocknest aeolian bedform in Gale crater. Analysis of the soil with the Chemistry and Mineralogy (CheMin) x-ray diffraction (XRD) instrument revealed plagioclase (~An57), forsteritic olivine (~Fo62), augite, and pigeonite, with minor K-feldspar, magnetite, quartz, anhydrite, hematite, and ilmenite. The minor phases are present at, or near, detection limits. The soil also contains 27 ± 14 weight percent x-ray amorphous material, likely containing multiple Fe(3+)- and volatile-bearing phases, including possibly a substance resembling hisingerite. The crystalline component is similar to the normative mineralogy of certain basaltic rocks from Gusev crater on Mars and of martian basaltic meteorites. The amorphous component is similar to that found on Earth in places such as soils on the Mauna Kea volcano, Hawaii.

13.
Science ; 341(6153): 1239505, 2013 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-24072928

RESUMO

The Rocknest aeolian deposit is similar to aeolian features analyzed by the Mars Exploration Rovers (MERs) Spirit and Opportunity. The fraction of sand <150 micrometers in size contains ~55% crystalline material consistent with a basaltic heritage and ~45% x-ray amorphous material. The amorphous component of Rocknest is iron-rich and silicon-poor and is the host of the volatiles (water, oxygen, sulfur dioxide, carbon dioxide, and chlorine) detected by the Sample Analysis at Mars instrument and of the fine-grained nanophase oxide component first described from basaltic soils analyzed by MERs. The similarity between soils and aeolian materials analyzed at Gusev Crater, Meridiani Planum, and Gale Crater implies locally sourced, globally similar basaltic materials or globally and regionally sourced basaltic components deposited locally at all three locations.

14.
Interv Neuroradiol ; 17(2): 137-46, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21696650

RESUMO

A significant percentage of children with hemangiomas may have PHACES syndrome which refers to the association of posterior fossa malformations, facial hemangiomas, arterial cerebrovascular abnormalities, cardiovascular anomalies, eye abnormalities and ventral defects like sternal clefting or supraumbilical raphe. A variety of factors have led to under diagnosis of PHACES syndrome in the past including lack of awareness and limited imaging modalities. Also, patients with PHACES syndrome with arterial cerebrovascular abnormalities can present with acute ischemic stroke. However, these patients usually present before one year of age. We describe a 29-year-old woman with no history of cerebrovascular disease who initially presented with symptoms of a stroke and was subsequently diagnosed to have PHACES syndrome exhibiting an array of multiple unusual imaging findings. We also discuss the current literature and recommendations about PHACES syndrome.


Assuntos
Coartação Aórtica/patologia , Transtornos Cerebrovasculares/patologia , Fossa Craniana Posterior/anormalidades , Anormalidades do Olho/patologia , Hemangioma/patologia , Síndromes Neurocutâneas/patologia , Adulto , Coartação Aórtica/diagnóstico por imagem , Angiografia Cerebral , Transtornos Cerebrovasculares/diagnóstico por imagem , Fossa Craniana Posterior/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Anormalidades do Olho/diagnóstico por imagem , Feminino , Humanos , Síndromes Neurocutâneas/diagnóstico por imagem , Tomografia Computadorizada por Raios X
15.
J Phys Chem A ; 114(23): 6550-7, 2010 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-20499911

RESUMO

The calculated electron density distribution for orpiment, As(2)S(3), reveals that As-S, S-S, and As-As bond paths are associated with the experimental interlayer directed bonded interactions detected in a combined infrared and Raman study. The successful modeling of the infrared- and Raman-determined interlayer bonded interactions together with bond paths and the structuralization of a variety of inorganic molecules in terms of "key-lock" bond path mainstays support the argument that van der Waals forces in inorganic molecular crystals are directional.

16.
Osteoporos Int ; 21(10): 1769-80, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20101492

RESUMO

UNLABELLED: During the first year of Prospective Observational Scientific Study Investigating Bone Loss Experience (POSSIBE US), many women transitioned (i.e., discontinued or switched) from their baseline osteoporosis medication. Participants not on stable therapy at entry, with side effects, and with poor physical status were at higher risk of transitioning. Understanding factors associated with persistence may lead to improved outcomes. INTRODUCTION: Postmenopausal osteoporosis (PMO) medication use patterns may differ by treatment history and drug class. We describe these patterns among patients in primary care settings using patient-reported data. METHODS: Data from 3,006 participants of the POSSIBLE US were used to estimate the probability of a baseline PMO medication transition (i.e., discontinuation or switch) and hazard ratios (HRs) for predictors of these transitions. RESULTS: One year after study entry, the probability of persisting with a baseline medication was 66% (95% CI: 64-68%). After adjusting for age and osteoporosis diagnosis, factors at entry independently associated with a higher risk of baseline medication transition were treatment status cohort, side effect severity, and OPAQ-SV physical function score. Compared to participants stable on therapy at entry, others had a higher risk, ranging from HR = 1.59 (95% CI: 1.36-1.85) for those new to therapy to HR = 2.00 (95% CI: 1.27-3.15) for those who recently augmented therapy at entry. Participants reporting moderate (HR = 1.31, 95% CI: 1.09-1.57) or severe (HR = 1.88, 95% CI: 1.49-2.39) side effects had a higher risk than those not reporting side effects. Participants reporting Osteoporosis Assessment Questionnaire-Short Version physical function scores in the lowest tertile had a higher risk (HR = 1.27, 95% CI: 1.07-1.52) than those reporting scores in the highest tertile. CONCLUSION: Baseline osteoporosis medication transitions were common in the first year of POSSIBLE US. Participants not on stable therapy at entry, or who reported severe side effects, or had poor physical health status were at higher risk for these transitions.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Substituição de Medicamentos/estatística & dados numéricos , Osteoporose Pós-Menopausa/tratamento farmacológico , Idoso , Conservadores da Densidade Óssea/efeitos adversos , Uso de Medicamentos/estatística & dados numéricos , Escolaridade , Métodos Epidemiológicos , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/etnologia , Osteoporose Pós-Menopausa/fisiopatologia , Resultado do Tratamento
17.
Osteoporos Int ; 21(7): 1215-26, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19798460

RESUMO

UNLABELLED: In this Phase 2 study of postmenopausal women with low bone, arzoxifene (a selective estrogen receptor modulator (SERM)) significantly reduced bone turnover marker levels and increased bone mineral density (BMD) versus placebo. Arzoxifene generally had greater effects on bone turnover and BMD than raloxifene, a SERM in current clinical use. Arzoxifene's safety profile appeared similar to raloxifene. INTRODUCTION: This 6-month, Phase 2, double-blind, placebo- and raloxifene-controlled study was designed to assess the effects of arzoxifene on bone turnover and overall safety in postmenopausal women with low bone mass. METHODS: Postmenopausal women (N = 219; mean age, 59 years) with a T-score between -1 and -2.5 were randomly assigned to daily arzoxifene 5, 10, 20, or 40 mg, raloxifene 60 mg, or placebo. All received daily calcium. RESULTS: All arzoxifene doses significantly reduced osteocalcin (primary endpoint), type 1 collagen C-telopeptide, bone specific alkaline phosphatase, and procollagen type I amino-terminal propeptide versus placebo, and increased lumbar spine BMD. Arzoxifene generally had greater effects on bone turnover and BMD than raloxifene. Arzoxifene decreased cholesterol, low-density lipoprotein cholesterol, and fibrinogen versus placebo. Endometrial thickness change with arzoxifene was not significantly different from placebo or raloxifene; no cases of endometrial hyperplasia or adenocarcinoma were observed. Adverse event reporting with arzoxifene was similar to that with raloxifene, as were hot flush and night sweat reporting. CONCLUSIONS: Arzoxifene suppressed bone turnover and increased BMD. Within the limitations of this study, the endometrial safety profile of arzoxifene appeared similar to that of raloxifene. While no clear dose effect was evident, arzoxifene 20 and 40 mg/day appeared the optimal doses for reducing bone turnover.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Lipídeos/sangue , Osteoporose Pós-Menopausa/tratamento farmacológico , Piperidinas/uso terapêutico , Tiofenos/uso terapêutico , Idoso , Biomarcadores/sangue , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , Remodelação Óssea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Endométrio/efeitos dos fármacos , Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/fisiopatologia , Piperidinas/administração & dosagem , Piperidinas/efeitos adversos , Cloridrato de Raloxifeno/uso terapêutico , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Tiofenos/administração & dosagem , Tiofenos/efeitos adversos , Sistema Vasomotor/efeitos dos fármacos , Sistema Vasomotor/fisiopatologia
18.
J Phys Chem A ; 113(4): 736-49, 2009 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-19123777

RESUMO

Bond paths, local energy density properties, and Laplacian, L(r) = -wedge(2)rho(r), composite isosurfaces of the electron density distributions were calculated for the intramolecular and intermolecular bonded interactions for molecular solids of As(2)O(3) and AsO(2) composition, an As(2)O(5) crystal, a number of arsenate molecules, and the arsenic metalloid, arsenolamprite. The directed intermolecular van der Waals As-O, O-O, and As-As bonded interactions are believed to serve as mainstays between the individual molecules in each of the molecular solids. As-O bond paths between the bonded atoms connect Lewis base charge concentrations and Lewis acid charge depletion domains, whereas the O-O and As-As paths connect Lewis base pair and Lewis acid pair domains, respectively, giving rise to sets of intermolecular directed bond paths. The alignment of the directed bond paths results in the periodic structures adopted by the arsenates. The arrangements of the As atoms in the claudetite polymorphs of As(2)O(3) and the As atoms in arsenolamprite are similar. Like the As(2)O(3) polymorphs, arsenolamprite is a molecular solid connected by relatively weak As-As intermolecular directed van der Waals bond paths between the layers of stronger As-As intramolecular bonded interactions. The bond critical point and local energy density properties of the intermolecular As-As bonded interactions in arsenolamprite are comparable with the As-As interactions in claudetite I. As such, the structure of claudetite I can be viewed as a stuffed derivative of the arsenolamprite structure with O atoms between pairs of As atoms comprising the layers of the structure. The cubic structure adopted by the arsenolite polymorph can be understood in terms of sets of directed acid-base As-O and base-base O-O pair domains and bond paths that radiate from the tetrahedral faces of its constituent molecules, serving as face-to-face key-lock mainstays in forming a periodic tetrahedral array of molecules rather than one based on some variant of close packing. The relatively dense structure and the corrugation of the layers in claudetite I can also be understood in terms of directed van der Waals As-O bonded interactions. Our study not only provides a new basis for understanding the crystal chemistry and the structures of the arsenates, but it also calls for a reappraisal of the concept of van der Waals bonded interactions, how the structures of molecular solids are viewed, and how the molecules in these solids are bonded in a periodic structure.

19.
Appl Spectrosc ; 62(7): 766-72, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18935826

RESUMO

The first observation of the vibrational spectrum of the synthetic pyroxene Li-kosmochlor (LiCrSi2O6) is reported herein. The Raman and visible spectra are reported as a function of pressure. Though the pyroxene retains its P21/c symmetry, changes in the Raman spectra are observed between 6.8 and 7.7 GPa, possibly due to the formation of an additional bond between Li and O3 or some other transition that retains the mineral's P21/c space group. Splitting of the peak appearing at approximately 700 cm(-1), used to characterize the P21/c phase in other studies, is not observed. Comparison is made with the Raman spectra of LiAlSi2O6 and LiFeSi2O6 in the P21/c phase and the visible spectra of NaCrSi2O6 at high pressures.


Assuntos
Minerais/química , Análise Espectral Raman/métodos , Luz , Pressão , Espalhamento de Radiação
20.
J Phys Chem A ; 112(37): 8811-23, 2008 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-18714960

RESUMO

Bond critical point (bcp) and local energy density properties for the electron density (ED) distributions, calculated with first-principle quantum mechanical methods for divalent transition metal Mn-, Co-, and Fe-containing silicates and oxides are compared with experimental model ED properties for tephroite, Mn 2SiO 4, fayalite, Fe 2SiO 4, and Co 2SiO 4 olivine, each determined with high-energy synchrotron single-crystal X-ray diffraction data. Trends between the experimental bond lengths, R(M-O), (M = Mn, Fe, Co), and the calculated bcp properties are comparable with those observed for non-transition M-O bonded interactions. The bcp properties, local total energy density, H( r c), and bond length trends determined for the Mn-O, Co-O, and Fe-O interactions are also comparable. A comparison is also made with model experimental bcp properties determined for several Mn-O, Fe-O, and Co-O bonded interactions for selected organometallic complexes and several oxides. Despite the complexities of the structures of the organometallic complexes, the agreement between the calculated and model experimental bcp properties is fair to good in several cases. The G( r c)/rho( r c) versus R(M-O) trends established for non-transition metal M-O bonded interactions hold for the transition metal M-O bonded interactions with G( r c)/rho( r c) increasing in value as H( r c) becomes progressively more negative in value, indicating an increasing shared character of the interaction as G( r c)/rho( r c) increases in value. As observed for the non-transition metal M-O bonded interactions, the Laplacian, nabla (2)rho( r c), increases in value as rho( r c) increases and as H( r c) decreases and becomes progressive more negative in value. The Mn-O, Fe-O, and Co-O bonded interactions are indicated to be of intermediate character with a substantial component of closed-shell character compared with Fe-S and Ni-S bonded interactions, which show greater shared character based on the | V( r c)|/ G( r c) bond character indicator. The atomic charges conferred on the transition metal atoms for the three olivines decrease with increasing atomic number from Mn to Fe to Co as the average M-O bond lengths decrease from 2.219 to 2.168 to 2.128 A, respectively.

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