bluuebunny/crossref_metadata_2025 huggingface dataset:
Consumo de alimentos de risco e proteção para doenças cardiovasculares entre funcionários públicos
Authors: Neumann Africa Isabel de la Cruz Perez , Shirassu Mirian Matsura , Fisberg Regina Mara
Published: April 2006

OBJETIVO: Descrever o consumo de alimentos de risco e proteção para doenças cardiovasculares segundo escolaridade e renda familiar entre funcionários públicos. MÉTODOS: Realizou-se inquérito epidemiológico entre funcionários de sedes de secretarias estaduais do município de São Paulo, ambos os sexos, acima de 18 anos por meio de amostra aleatória (n=1 271) representativa do total de 4 665. Foram obtidas informações socioeconômicas, de estilo de vida e consumo alimentar, bem como morbidades referidas. O consumo alimentar foi avaliado por meio do questionário de freqüência alimentar. RESULTADOS: Verificou-se a presença dos fatores de risco: sedentarismo (88%), sobrepeso/obesidade (36%), tabagismo (27%) e doenças do aparelho circulatório (30%). A média do consumo de alimentos de risco - ricos em gorduras saturadas, sódio e açúcares - foi estatisticamente maior entre os indivíduos de escolaridade fundamental e de renda familiar até três salários mínimos. Quanto aos alimentos protetores - fontes de fibra dietética, vitaminas, minerais, ácidos graxos insaturados e monoinsaturados, e fitoquímicos - a média de consumo foi estatisticamente maior entre os funcionários de escolaridade superior e renda superior a seis salários mínimos. CONCLUSÃO: Entre os indivíduos com nível de escolaridade fundamental e menor renda familiar há predominância de consumo de alimentos de risco para doenças cardiovasculares, além de outros fatores de risco associados. Os programas de intervenção devem priorizar tal segmento da população.
Efeito de um hidrolisado de proteínas de soro de leite e de seus peptídeos na proteção de lesões ulcerativas da mucosa gástrica de ratos
Authors: Pacheco Maria Teresa Bertoldo , Bighetti Érica , Antônio Márcia , Carvalho João Ernesto de , Rosaneli Caroline Filla , Sgarbieri Valdemiro Carlos
Published: April 2006

OBJETIVO: Avaliar a atividade do hidrolisado das proteínas de soro de leite bovino e uma fração de peptídeos de baixo peso molecular (peso molecular <1kDa), na proteção do epitélio da mucosa do estômago de ratos Wistar adultos contra o processo ulcerativo, induzidos por três diferentes agentes. MÉTODOS: Nesse estudo foram utilizados os modelos de indução de úlcera pelo antiinflamatório indometacina (30mg/kg de peso), por etanol absoluto (1ml/animal) e por estresse causado por imobilização e frio (4ºC/2h) em ratos Wistar adultos. RESULTADO: O hidrolisado protéico de soro de leite foi obtido por tratamento com pancreatina, ao grau de hidrólise de 20%, e fracionado em membrana de fluxo tangencial com faixa de corte de 1kDa, para obtenção de uma fração contendo peptídeos de baixo peso molecular denominada peptídeos do hidrolisado protéico de soro (<1kDa). A administração aguda do hidrolisado protéico de soro, de acordo com o modelo etanol, resultou em 65,5% de redução dos índices de lesões ulcerativas, sendo obtida 77,4% de inibição em dose dupla. CONCLUSÃO: O efeito citoprotetor dos peptídeos de baixo peso molecular foi mais elevado para o modelo de indução por antiinflamatório, em relação ao hidrolisado integral, tanto em dose única como em dupla (53,1% e 71,6% de redução dos índices de lesões ulcerativas, respectivamente). Não foi constatada atividade protetora em modelos de úlcera induzidos por estresse.
O modelo transteorético aplicado ao consumo de frutas e hortaliças em adolescentes
Authors: Oliveira Maria do Carmo Fontes de , Duarte Gisele Kuhlmann
Published: April 2006

OBJETIVO: Identificar a relação entre dois constructos do Modelo Transteorético - estágios e processos de mudança - quanto ao consumo de frutas e de hortaliças por adolescentes. MÉTODOS: Em desenho transversal, foi aplicado um questionário a 61 adolescentes, verificando que o uso do processo autoliberação se distinguiu significativamente (p<0,05) em todos os estágios de mudança no consumo de frutas e de hortaliças. RESULTADO: O processo suporte social apresentou diferenças significativas (p<0,05) no seu uso entre estágios pré-contemplação/contemplação e preparação apenas no consumo de frutas. Quanto ao uso do processo auto-reavaliação, foram encontradas diferenças significativas (p<0,05) entre os estágios pré-contemplação/contemplação e preparação no consumo de hortaliças. CONCLUSÃO: Concluiu-se que alguns processos específicos de mudança eram utilizados pelos adolescentes ao se moverem por meio dos estágios de mudança. Intervenções empregando tais processos devem ser realizadas para possibilitar avanços nos estágios de mudança do consumo de frutas e de hortaliças.
Sistema multimídia de apoio à decisão em procedimentos de higiene para unidades de alimentação e nutrição
Authors: Antunes Maria Aparecida , Andrade Nélio José , Silva Carlos Arthur Barbosa , Azeredo Raquel Monteiro Cordeiro , Lopes Franceline Aparecida
Published: April 2006

É objetivo deste estudo desenvolver um sistema multimídia com a finalidade de subsidiar a melhoria de procedimentos de higiene em Unidades de Alimentação e Nutrição. O sistema Clean Up, composto de várias bases de conhecimento e informações interligadas e organizadas em módulos foi avaliado por 30 usuários que responderam ao teste de aceitação baseado na Escala Likert modificada, com os atributos próprios de escala hedônica, com notas de 1 a 9, para classificação que varia de "extremamente bom" a "extremamente ruim". A partir dos dados coletados foram calculadas a moda e os valores máximo e mínimo das notas para cada atributo julgado pelos avaliadores. A nota 8 foi a mais freqüente, classificando os módulos como "muito bom", segundo a escala Likert. É também função do multimídia entreter o usuário. As cores, sons, filmes, imagens devem surpreender e criar expectativas positivas, aumentando a vontade de explorar o conteúdo durante a aquisição do conhecimento.
Abiotic factors influencing tropical dry forests regeneration
Authors: Ceccon Eliane , Huante Pilar , Rincón Emanuel
Published: April 2006

Tropical dry forests represent nearly half the tropical forests in the world and are the ecosystems registering the greatest deterioration from the anthropogenic exploitation of the land. This paper presents a review on the dynamics of tropical dry forests regeneration and the main abiotic factors influencing this regeneration, such as seasonal nature, soil fertility and humidity, and natural and anthropic disturbances. The main purpose is to clearly understand an important part of TDF succession dynamics.
Characterization of isoforms of activin receptor-interacting protein 2 that augment activin signaling
Authors: Liu Z H , Tsuchida K , Matsuzaki T , Bao Y L , Kurisaki A , Sugino H
Published: April 2006

Activin type II receptors (ActRIIs) including ActRIIA and ActRIIB are serine/threonine kinase receptors that form complexes with type I receptors to transmit intracellular signaling of activins, nodal, myostatin and a subset of bone morphogenetic proteins. ActRIIs are unique among serine/threonine kinase receptors in that they associate with proteins having PSD-95, Discs large and ZO-1 (PDZ) domains. In our previous studies, we reported specific interactions of ActRIIs with two independent PDZ proteins named activin receptor-interacting proteins 1 and 2 (ARIP1 and ARIP2). Overexpression of both ARIP1 and ARIP2 reduce activin-induced transcription. Here, we report the isolation of two isoforms of ARIP2 named ARIP2b and 2c. ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. ARIP2 and its isoforms have one PDZ domain in the NH2-terminal region, and interact with ActRIIA. Although PDZ domains containing GLGF motifs of ARIP2b and 2c are identical to that of ARIP2, their COOH-terminal sequences differ from that of ARIP2. Interestingly, unlike ARIP2, overexpression of ARIP2b or 2c did not affect ActRIIA internalization. ARIP2b/2c inhibit inhibitory actions of ARIP2 on activin signaling. ARIP2 is widely distributed in mouse tissues. ARIP2b/2c is expressed in more restricted tissues such as heart, brain, kidneys and liver. Our results indicate that although both ARIP2 and ARIP2b/2c interact with activin receptors, they regulate ActRIIA function in a different manner.
Growth differentiation factor-9 has divergent effects on proliferation and steroidogenesis of bovine granulosa cells
Authors: Spicer L J , Aad P Y , Allen D , Mazerbourg S , Hsueh A J
Published: April 2006

In addition to gonadotropins, steroidogenesis and proliferation of granulosa cells during follicular development are controlled by a number of intraovarian factors including growth differentiation factor-9 (GDF-9), bone morphogenetic protein-4 (BMP-4), and IGF-I. The objective of this study was to determine the effect of GDF-9 and BMP-4 and their interaction with IGF-I and FSH on ovarian granulosa cell function in cattle. Granulosa cells from small (1–5 mm) and large (8–22 mm) follicles were collected from bovine ovaries and cultured for 48 h in medium containing 10% fetal calf serum and then treated with various hormones in serum-free medium for an additional 48 h. We evaluated the effects of GDF-9 (150–600 ng/ml) and BMP-4 (30 ng/ml) during a 2-day exposure on hormone-induced steroidogenesis and cell proliferation. In FSH plus IGF-I-treated granulosa cells obtained from small follicles, 300 ng/ml GDF-9 reduced (P<0.05) progesterone production by 15% and 600 ng/ml GDF-9 completely blocked (P<0.01) the IGF-I-induced increase in progesterone production. In comparison, 300 and 600 ng/ml GDF-9 decreased (P<0.05) estradiol production by 27% and 71% respectively, whereas 150 ng/ml GDF-9 was without effect (P>0.10). Treatment with 600 ng/ml GDF-9 increased (P<0.05) numbers (by 28%) of granulosa cells from small follicles. In the same cells treated with FSH but not IGF-I, co-treatment with 600 ng/ml GDF-9 decreased (P<0.05) progesterone production (by 28%), increased (P<0.05) cell numbers (by 60%), and had no effect (P>0.10) on estradiol production. In FSH plus IGF-I-treated granulosa cells obtained from large follicles, GDF-9 caused a dose-dependent decrease (P<0.05) in IGF-I-induced progesterone (by 13–48%) and estradiol (by 20–51%) production. In contrast, GDF-9 increased basal and IGF-I-induced granulosa cell numbers by over 2-fold. Furthermore, treatment with BMP-4 also inhibited (P<0.05) steroidogenesis by 27–42% but had no effect on cell numbers. To elucidate downstream signaling pathways, granulosa cells from small follicles were transfected with similar to mothers against decapentaplegics (Smad) binding element (CAGA)- or BMP response element (BRE)-promoter reporter constructs. Treatment with GDF-9 (but not BMP-4) activated the Smad3-induced CAGA promoter activity, whereas BMP-4 (but not GDF-9) activated the Smad1/5/8-induced BRE promoter activity. We have concluded that bovine granulosa cells are targets of both GDF-9 and BMP-4, and that oocyte-derived GDF-9 may simultaneously promote granulosa cell proliferation and prevent premature differentiation of the granulosa cells during growth of follicles, whereas theca-derived BMP-4 may also prevent premature follicular differentiation.
The ternary IGF complex influences postnatal bone acquisition and the skeletal response to intermittent parathyroid hormone
Authors: Yakar Shoshana , Bouxsein Mary L , Canalis Ernesto , Sun Hui , Glatt Vaida , Gundberg Caren , Cohen Pinchas , Hwang David , Boisclair Yves , LeRoith Derek , Rosen Clifford J
Published: April 2006

The role of circulating IGF-I in skeletal acquisition and the anabolic response to PTH is not well understood. We generated IGF-I-deficient mice by gene deletions of IGF ternary complex components including: (1) liver-specific deletion of the IGF-I gene (LID), (2) global deletion of the acid-labile (ALS) gene (ALSKO), and (3) both liver IGF-I and ALS inactivated genes (LA). Twelve-week-old male control (CTL), LID, ALSKO, and LA mice were treated with vehicle (VEH) or human PTH(1–34) for 4 weeks. VEH-treated IGF-I-deficient mice (i.e. LID, ALSKO and LA mice) exhibited reduced cortical cross-sectional area (P = 0.001) compared with CTL mice; in contrast, femoral trabecular bone volume fractions (BV/TV) of the IGF-I-deficient mice were consistently greater than CTL (P<0.01). ALSKO mice exhibited markedly reduced osteoblast number and surface (P<0.05), as well as mineral apposition rate compared with other IGF-I-deficient and CTL mice. Adherent bone marrow stromal cells, cultured in β-glycerol phosphate and ascorbic acid, showed no strain differences in secreted IGF-I. In response to PTH, there were both compartment- and strain-specific effects. Cortical bone area was increased by PTH in CTL and ALSKO mice, but not in LID or LA mice. In the trabecular compartment, PTH increased femoral and vertebral BV/TV in LID, but not in ALSKO or LA mice. In conclusion, we demonstrated that the presentation of IGF-I as a circulating complex is essential for skeletal remodeling and the anabolic response to PTH. We postulate that the ternary complex itself, rather than IGF-I alone, influences bone acquisition in a compartment-specific manner (i.e. cortical vs trabecular bone).
Peroxisome proliferator-activated receptors in reproductive tissues: from gametogenesis to parturition
Authors: Froment P , Gizard F , Defever D , Staels B , Dupont J , Monget P
Published: April 2006

Peroxisome proliferator-activated receptors (PPARα, PPARβ/δ and PPARγ) are a family of nuclear receptors that are activated by binding of natural ligands, such as polyunsaturated fatty acids or by synthetic ligands. Synthetic molecules of the glitazone family, which bind to PPARγ, are currently used to treat type II diabetes and also to attenuate the secondary clinical symptoms frequently associated with insulin resistance, including polycystic ovary syndrome (PCOS). PPARs are expressed in different compartments of the reproductive system (hypothalamus, pituitary, ovary, uterus and testis). Conservative functions of PPARs in mammalian species could be suggested through several in vivo and in vitro studies, especially in the ovary and during placental development. Several groups have described a strong expression of PPARγ in ovarian granulosa cells, and glitazones modulate granulosa cell proliferation and steroidogenesis in vitro. All these recent data raise new questions about the biologic actions of PPARs in reproduction and their use in therapeutic treatments of fertility troubles such as PCOS or endometriosis. In this review, we first describe the roles of PPARs in different compartments of the reproductive axis (from male and female gametogenesis to parturition), with a focus on PPARγ. Secondly, we discuss the possible molecular mechanisms underlying the effect of glitazones on PCOS. Like other ‘insulin sensitizer’ molecules, such as metformin, glitazones may in fact act directly on ovarian cells. Finally, we discuss the eventual actions of PPARs as mediators of environmental toxic substances for reproductive function.
Sublethal toxicity of trace metals to larvae of the blacklip abalone,Haliotis rubra
Authors: Gorski Jacquelle , Nugegoda Dayanthi
Published: April 2006

The availability of literature regarding sublethal and chronic toxicity of heavy metals to early life stages of marine species is restricted to a few species of invertebrate mollusks. The early life stage of abalone, an important gastropod both environmentally and commercially, has been involved in limited research investigating the effects of heavy metal toxicity. Fertilized eggs of Haliotis rubra were exposed to a range of dissolved nominal concentrations of cadmium, copper, iron, lead, mercury, and zinc in individual solutions for 48 h. After 48 h of exposure, the test was completed by recording survival success and morphological abnormalities of veliger larvae in each heavy metal treatment. The mean 48-h median effective concentrations affecting normal morphological development of veliger larvae determined in this test shows a decreasing order of toxicity of copper (7 μg/L), mercury (21 μg/L), zinc (35 μg/L), iron (4,102 μg/L), cadmium (4,515 μg/L), and lead (5,111 μg/L).
Effects of pulsed copper exposures on early life-stagePimephales promelas
Authors: Bearr Jonathan S. , Diamond Jerry , Latimer Henry , Bowersox Marcus
Published: April 2006

Effects of pulsed copper exposures were investigated using Pimephales promelas aged less than 24 h in short-term chronic testing (7 or 14 d) with moderately hard synthetic water. Concentrations tested were between the species mean chronic value (22 μg/L at a hardness of 100 mg/L as CaCO3) and the 7-d continuous exposure EC50 for survival (40 μg/L) to examine exposures that were not acutely toxic and representative of actual wastewater discharge permit exceedences. Factors tested included pulse duration, recovery time between pulses, and pulse frequency. Survival was the main endpoint affected in all treatments (analysis of variance, p < 0.05). Effects on fish biomass, independent of survival effects, were observed in only 2 of 86 treatments examined. Fish survival was negatively affected at average copper concentrations between 7 and 50% of the 7-d continuous exposure EC50. Exposures having a 48- to 96-h recovery time between pulses had less effect on fish survival than did treatments with shorter (12–24 h) or longer (>120 h) recovery times. Results suggest that the criteria averaging periods used in the United States, and the averaging periods typically used in wastewater discharge permit limits for copper, may not protect against effects of certain pulsed exposures.
Organohalogen contaminants and metabolites in beluga whale (Delphinapterus leucas) liver from two Canadian populations
Authors: McKinney Melissa A. , De Guise Sylvain , Martineau Daniel , Béland Pierre , Lebeuf Michel , Letcher Robert J.
Published: April 2006

Contaminants described as organochlorines (OCs; e.g., polychlorinated biphenyls [PCBs]) are present in tissues of marine mammals, including beluga whales (Delphinapterus leucas), but the complexity of contaminant exposure often is not fully known. The PCBs, OC pesticides, polybrominated diphenyl ether (PBDE) flame retardants, methylsulfonyl (MeSO2)- and hydroxy (OH)-PCB metabolites, and OH-PBDEs and methoxylated (MeO)-PBDEs were determined in the liver of beluga whales from two Canadian populations: the St. Lawrence Estuary (SLB; n = 6), and western Hudson Bay in the Canadian Arctic (CAB; n = 11). The ΣPCB, ΣDDT, and ΣPBDE concentrations were higher (p < 0.05) in SLB versus CAB. Of 18 detectable OH-PCBs in SLB (mainly 4-OH-CB107, 4-OH-CB112, and 4′-OH-CB120), only 4′-OH-CB120 was found in CAB. The ΣOH-PCB concentrations were less than 0.2% of the ΣPCBs in both populations but were higher (p < 0.05) in SLB (65 ± 22 ng/g lipid wt) than in CAB (3.1 ± 0.5 ng/g lipid wt). The ΣMeSO2-PCB concentrations were higher in SLB (3,801 ± 1,322 ng/g lipid wt) relative to CAB (77 ± 23 ng/g lipid wt) and were 11 and 4%, respectively, of the ΣPCB concentrations. Of the 15 OH-PBDEs, only two congeners were detectable, but not quantifiable (notably 2′-OH-BDE 68 and 6-OH-BDE 47), in animals from both populations. Of the 15 MeO-PBDEs, 4′-MeO-BDE 17 and 6-MeO-BDE 47 in the SLB (n = 2) and 2′-MeO-BDE 68 and 6-MeO-BDE 47 in the CAB (n = 2) had concentrations from 20 to 100 ng/g lipid weight. The OH-PBDEs and MeO-PBDEs most likely are of natural origin and accumulated in beluga whales, whereas the OH-PCBs and MeSO2-PCBs are metabolites derived from accumulated PCBs. Canadian beluga whale liver contains previously unidentified organohalogen contaminants and metabolites and, thus, a complexity of contaminant exposure that may be impacting the health of Canadian beluga whale populations.
Effects of exposure duration and recovery time during pulsed exposures
Authors: Zhao Yuan , Newman Michael C.
Published: April 2006

In pulsed toxicant exposures, the concentration, duration, and frequency of pulses can change through time. However, the conventional median lethal concentration (LC50) method cannot adequately predict the effects of pulsed exposure, because it is associated with fixed exposure duration and constant concentration and does not include postexposure (latent) mortality. Many studies that tried to address the effects of pulsed exposure only provided qualitative or semiquantitative predictions. Survival time experiments conducted here quantified the effect of exposure duration on latent mortality, and the effect of recovery time between two pulses on mortality during a second pulse also was examined. This was done by exposing amphipods (Hyalella azteca) to two contrasting toxicants, copper sulfate (CuSO4) and sodium pentachlorophenol (NaPCP). In the exposure duration experiments, the amphipods were exposed to two toxicant concentrations for three durations. No significant effect of duration on latent mortality was detected within the experimental range; however, duration still may need to be considered under other conditions. In the recovery time experiments, the amphipods were provided four recovery times, and their survivals during the second exposure were modeled. Recovery time had a significant effect on the second-exposure mortality. Given enough time, the amphipods could recover to a state similar to their original toxicant resistance state. The complete recovery time for CuSO4 was fivefold longer than that for NaPCP. It is important to quantify the effects of latent mortality, pulse duration and concentration, and recovery time for pulsed exposures. Survival analysis provides a better way to address these issues than does the conventional LC50 method.
Sensitivity of brain cholinesterase activity to diazinon (BASUDIN 50EC) and fenobucarb (BASSA 50EC) insecticides in the air-breathing fishChanna striata(Bloch, 1793)
Authors: Van Cong Nguyen , Phuong Nguyen Thanh , Bayley Mark
Published: April 2006

With the expansion of agricultural areas within the Mekong River Delta in Vietnam, a concurrent, dramatic increase has occurred in agrochemical usage. To date, little consideration has been given to the negative impacts of this agricultural activity on the aquatic resources of the region. Both acute toxicity and subacute effects on brain cholinesterase (ChE) of two of the most commonly used insecticides, diazinon and fenobucarb, on adult native snakehead (Channa striata) were evaluated in a static, nonrenewable system, the environmental parameters of which, such as dissolved oxygen, water temperature, and pH, fluctuated similarly to field conditions. Four levels of insecticides, from 0.008 to 0.52 mg/L (for diazinon) and from 0.11 to 9.35 mg/L (for fenobucarb), were tested to assess the effects on the brain ChE activity of the snakehead up to 30 and 10 d for diazinon and fenobucarb, respectively. Diazinon was highly toxic to this fish species, with a 96-h median lethal concentration (LC50) of only 0.79 mg/L, and it also caused long-term ChE inhibition, with activity still significantly inhibited by 30% after 30 d for the three highest concentrations. Fenobucarb was less toxic to this species, with a 96-h LC50 of 11.4 mg/L. Fenobucarb caused more rapid ChE inhibition but also rapid recovery. The results of the present study indicate an urgent need to regulate the usage of these pesticides in the Mekong River Delta.
Acute and chronic effects of pulse exposure ofDaphnia magnato dimethoate and pirimicarb
Authors: Andersen Tobias Henrik , Tjørnhøj Rikke , Wollenberger Leah , Slothuus Tina , Baun Anders
Published: April 2006

Short-term ( <48 h) and long-term (21 d) effects of dimethoate and pirimicarb were studied in Daphnia magna exposed to pulses of 0.5 to 8 h in duration. During a 21-d postexposure observation period, the following parameters were monitored: Mortality, mobility, day for first offspring, animal size, weight of offspring and adults, and number of offspring produced. In general, animals exposed to a single pulse of dimethoate or pirimicarb regained mobility after 24 to 48 h in clean media. Animals exposed to repeated pulses of dimethoate did not recover mobility during a 48-h postexposure observation period, and mortality was significantly increased. Animals exposed to two pulses of pirimicarb showed less recovery of mobility compared with those exposed to one pulse. Exposure of D. magna to 30 mg/L of dimethoate or 100 μg/L of pirimicarb for 2 to 6 h resulted in a significant reduction in the number of offspring and in the average weight of offspring. The average body length was reduced after pulse exposure to 30 mg/L of dimethoate for 3 h or 70 μg/L of pirimicarb for 4 h, and these exposure concentrations caused a delay in the day for first offspring at exposure durations of 2 to 6 h. The most important new findings in the present study are that short-term (<4 h) pulse exposure of neonates to acetylcholinesterase-inhibiting pesticides caused reproductive damage in D. magna and that repeated-pulse exposure significantly increased mortality in animals that apparently had recovered after a single-pulse exposure.
Genetic overlap between P300, P50, and duration mismatch negativity
Authors: Hall Mei Hua , Schulze Katja , Bramon Elvira , Murray Robin M. , Sham Pak , Rijsdijk Frühling
Published: April 2006

Mismatch Negativity (MMN), P300, and P50 suppression event‐related potential (ERP) components measure intermediate stages of information processing but little is known of how they relate to each other genetically. The present study used multivariate genetic model fitting analytic techniques in 46 monozygotic and 32 dizygotic twin pairs. P300, P50 suppression, and MMN were recorded using a 19‐channel electroencephalograph (EEG). Zygosity was determined using DNA genotyping. Little evidence for either genetic or environmental association between each of the three ERP paradigms was found. This result suggests that P300, MMN, and P50 suppression serve to evaluate different brain information processing functions that may be mediated by distinct neurobiological mechanisms which in turn are influenced by different sets of genes. Within paradigm, P300 amplitude and latency shared about half of their genetic effects. © 2006 Wiley‐Liss, Inc.
Synthesis and Anticoagulant Activities of Substituted 2,4‐Diketochromans, Biscoumarins, and Chromanocoumarins
Authors: Manolov Ilia , Maichle‐Moessmer Caecilia , Nicolova Irina , Danchev Nicolay
Published: April 2006

Different substituted 2,4‐diketochromans, biscoumarins, and chromanocoumarins are the final products when 4‐hydroxycoumarin and aromatic aldehydes containing hydroxyl group in o‐, m,‐ or p‐position condense in boiling ethanol. We synthesized 14 compounds. Three of them are described for the first time. The X‐ray crystal structure analysis of 3‐[6‐oxo‐(6H, 7H)‐benzopyrano[4,3‐b]benzopyran‐7‐yl]‐4‐hydroxy‐2H‐1‐benzopyran‐2‐one 1 confirmed the structure of this compound. Acute toxicity studies of the compounds were performed on mice by oral and intraperitoneal administration. A comparative pharmacological study of the in vivo anticoagulant effect of the derivatives with respect to warfarin showed that the synthesized compounds have different anticoagulant activities. The most prospective compounds are 3‐(3′‐hydroxybenzylidene)‐2,4‐diketochroman 4 and 3,3′‐(2‐pyridylmethylene)‐bis‐4‐hydroxy‐2H‐1‐benzopyran‐2‐one 11 with low toxicity and dose‐dependent anticoagulant activity in vivo.
The Weighted Generalized Estimating Equations Approach for the Evaluation of Medical Diagnostic Test at Subunit Level
Authors: Lin Carol Y. , Barnhart Huiman X. , Kosinski Andrzej S.
Published: April 2006

Sensitivity and specificity are common measures used to evaluate the performance of a diagnostic test. A diagnostic test is often administrated at a subunit level, e.g. at the level of vessel, ear or eye of a patient so that the treatment can be targeted at the specific subunit. Therefore, it is essential to evaluate the diagnostic test at the subunit level. Often patients with more negative subunit test results are less likely to receive the gold standard tests than patients with more positive subunit test results. To account for this type of missing data and correlation between subunit test results, we proposed a weighted generalized estimating equations (WGEE) approach to evaluate subunit sensitivities and specificities. A simulation study was conducted to evaluate the performance of the WGEE estimators and the weighted least squares (WLS) estimators (Barnhart and Kosinski, 2003) under a missing at random assumption. The results suggested that WGEE estimator is consistent under various scenarios of percentage of missing data and sample size, while the WLS approach could yield biased estimators due to a misspecified missing data mechanism. We illustrate the methodology with a cardiology example. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Detection of Overexpressed COX‐2 in Precancerous Lesions of Hamster Pancreas and Lungs by Molecular Imaging: Implications for Early Diagnosis and Prevention
Authors: Schuller Hildegard M. , Kabalka George , Smith Gary , Mereddy Arjun , Akula Murthy , Cekanova Maria
Published: April 2006

The enzyme cyclooxygenase‐2 (COX‐2) is overexpressed in many cancers, cardiovascular disease, neurodegenerative disorders, and arthritis. Selective inhibitors of COX‐2 have been developed as therapeutics or preventive agents for these diseases. However, recent reports have revealed a significant increase in cardiovascular mortality in long‐term users of the COX‐2 inhibitors Vioxx and Celebrex, emphasizing the need for noninvasive tests that allow the identification of individuals whose COX‐2 levels are overexpressed prior to assignment to treatment with these drugs. In this study, we have prepared a radioiodinated analogue of the selective COX‐2 inhibitor celecoxib, and verified its binding to the COX‐2 enzyme in vitro. Biodistribution studies in hamsters demonstrated significantly higher levels of radiotracer in animals treated with the tobacco carcinogen NNK in lung, pancreas, and liver. Assessment of COX‐2 levels by whole‐body planar nuclear imaging two hours after injection of the radiotracer was suggestive of a distinct increase in COX‐2 in the pancreas and liver of a hamster treated for 10 weeks with NNK, in the lungs and liver of a second animal, and in the liver only, in two additional animals from the same treatment group. Immunostains showed selective overexpression of COX‐2 in pre‐neoplastic lesions of the pancreas and lungs in only those animals that showed tracer accumulation in these organs and in the livers of all NNK‐treated hamsters. Immunostains for COX‐1 yielded detectable reactions in the intestinal epithelium but not in pancreas, lungs, or liver, supporting the specificity of the tracer for COX‐2. Our data provide proof of principle for the hypothesis that molecular imaging with radiolabeled COX‐2 inhibitors can be used for the noninvasive monitoring of overexpressed COX‐2 levels.
Cancer‐specific survival and predictors of prostate‐specific antigen recurrence and survival in patients with seminal vesicle invasion after radical prostatectomy
Authors: Secin Fernando P. , Bianco Fernando J. , Vickers Andrew J. , Reuter Victor , Wheeler Thomas , Fearn Paul A. , Eastham James A. , Scardino Peter T.
Published: April 2006

BACKGROUND

The objectives of the current study were to determine the long‐term biochemical recurrence (BCR) and cancer‐specific survival (CSS) rates for men with seminal vesicle invasion (SVI) and to identify risk factors for freedom from BCR and CSS in patients who received treatment in the prostate‐specific antigen era and who had SVI identified at the time of radical prostatectomy (RP).

METHODS

Prospective clinical, pathologic, and outcome data were collected for 5377 men who underwent RP between June 1983 and August 2004. There were 936 patients who were excluded because they received treatment before RP. Multivariable analysis was used to identify the factors that predicted BCR and CSS.

RESULTS

Among 4441 eligible patients, 387 patients (8.7%) had SVI, and 91 of those 387 patients (24%) had lymph node involvement (LNI). In total, 210 patients experienced BCR. For patients without LNI, the 10‐year and 15‐year freedom from BCR rates were 36% and 32%, respectively, and the corresponding CSS rates were 89% and 81%, respectively. For the 91 men who had SVI and LNI, the 10‐year BCR‐free probability was 10%, but the 10‐year CSS probability was 74%. By 10 years, patients with LNI were 3 times more likely to die from cancer than from other causes; nonetheless, 66% of patients were alive despite their advanced stage. The preoperative prostate‐specific antigen level, extracapsular extension, LNI, and Gleason grade were associated independently with BCR. Gleason scores of 8 to 10 and LNI were significant predictors of CSS.

CONCLUSIONS

SVI does not invariably signal BCR or death from cancer in patients who undergo RP and pelvic lymph node dissection. Fifteen years later, approximately 33% of men with SVI and negative lymph nodes are expected remain free of BCR, and CSS was surprisingly good. Cancer 2006. © 2006 American Cancer Society.
Phase I/II study of a combined gemcitabine, etoposide, and cisplatin chemotherapy regimen for metastatic urothelial carcinoma
Authors: Tsukamoto Tetsuro , Yonese Junji , Ohkubo Yuhei , Fukui Iwao
Published: April 2006

BACKGROUND

The authors attempted to determine the maximum tolerated dose (MTD) of gemcitabine in combination with etoposide and cisplatin as a chemotherapy regimen and investigated the safety and antitumor activity with the recommended doses of gemcitabine with etoposide and cisplatin for patients with metastatic urothelial carcinoma.

METHODS

Patients age 75 years or younger with measurable lesions, creatinine clearance ≥50 mL per minute, and adequate bone marrow and hepatic function were studied. Etoposide and cisplatin were given on Days 1 through 3 at fixed doses of 75 mg/m2 and 25 mg/m2, respectively, and gemcitabine was given on Days 1, 8, and 15. In the Phase I component, gemcitabine was administered at increasing doses from 600 mg/m2. Cycles were repeated every 28 days unless progressive disease was encountered.

RESULTS

In Phase I, with the initially fixed doses of etoposide and cisplatin, the MTD of gemcitabine could not be determined because of the occurrence of dose‐limiting toxicity at Level 1 in all 3 patients. When the doses of etoposide and cisplatin were modified to 60 mg/m2 and 20 mg/m2, respectively, the MTD of gemcitabine was 1000 mg/m2. Next, 19 additional patients were entered into Phase II with the recommended gemcitabine dose of 800 mg/m2, and 20 patients in all were treated at this dose level. The main toxicity was bone marrow suppression, with Grade 3 or 4 neutropenia and thrombocytopenia recognized in 20 patients (100%) and 14 patients (70%), respectively, although no toxic deaths occurred. In total, all 31 patients at all dose levels had an assessable response, with 6 complete responses and 15 partial responses observed, for an overall response rate of 67.7%. Patients who had visceral metastasis had a significantly worse response rate than patients who had lymph node metastasis alone (50.0% vs. 78.9%; P = .042). The response rate (66.7%) for 21 patients who received prior chemotherapy was not different from that for 10 chemotherapy‐naive patients. The median survival for all patients was 13.1 months, and 4 patients survived for >2 years with no evidence of disease. Patients younger than age 65 years had significantly better survival than patients age 65 years or older (P = .026).

CONCLUSIONS

Although bone marrow toxicity was considerable, combination chemotherapy with gemcitabine, etoposide, and cisplatin appeared to be very active in patients with urothelial carcinoma and may be especially promising for younger patients, although further study is warranted. Cancer 2006. © 2006 American Cancer Society.
A comparison of ProOsteon, DBX, and collagraft in a rabbit model
Authors: Leupold John A. , Barfield William R. , An Yuehuei H. , Hartsock Langdon A.
Published: April 2006

Many bone graft substitutes (BGSs) have been developed and are commercially available. These products differ in the tailoring of their properties, including size, form, osteoconductivity, osteoinductivity, and resorption kinetics. Differential enhancement of these properties may optimize the performance of these materials for varying applications. BGSs offer an opportunity to lessen morbidity of harvesting and use of autogenous and/or allograft bone. The purpose of this study is to quantitatively compare the magnitude of bony ingrowth and biodegradation of different commercially available BGS materials in a rabbit femoral defect model. BGSs from each of three classes (ceramic (ProOsteon), demineralized bone matrix (DBX), and composite (Collagraft)) were implanted in cylindrical defects in bilateral femoral condyles of 12 adult New Zealand White rabbits. Each of the three BGS materials and the empty controls were compared. The specimens were harvested at 3 months postimplantation for radiographic and histologic evaluation. Histomorphometry yielded resorption of graft material remaining in the index defect. Magnitude of bony ingrowth was assessed based on an 8‐bit 256 densitometry model. Histomorphometric analysis of the data demonstrated statistical differences in the resorption and magnitude of bony ingrowth of the three BGS materials. The three BGS were significantly different for ingrowth (p = 0.046) when using the Wilcoxon Test. The ceramic graft material averaged 47% bony ingrowth. Rabbit‐based DBX material showed extensive osseous ingrowth (35%) and the composite graft material demonstrated significant bony ingrowth (56%). The control, as anticipated, showed the least amount of bony ingrowth (29%). Fisher's Exact Test yielded statistical differences (p = 0.0003) when comparisons for resorption were conducted. An ideal BGS material should be biocompatible, be able to withstand the local load environment for a given application, degrade in concert with bony replacement, and be both osteoinductive and osteoconductive. This in‐vivo, head‐to‐head comparison of three commercially available BGS materials in an animal model compares these characteristics and demonstrates differences between them, which may act as a guide in the use of these products in human applications. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
A novel polymer for potential use in a trileaflet heart valve
Authors: Gallocher Siobhain L. , Aguirre Andres F. , Kasyanov Vladimir , Pinchuk Leonard , Schoephoerster Richard T.
Published: April 2006

A novel polyolefin, poly(styrene‐b‐isobutylene‐b‐styrene) (Quatromer™), is being proposed as a viable polymer for use in trileaflet heart valves because of its oxidative stability. The current study was designed to assess the polymer's hemocompatibility and mechanical durability. Mechanical characterization included static tensile tests and dynamic tension–tension and bending fatigue tests, where the properties of isotropic and composite (polypropylene (PP) embedded) Quatromer specimens were compared with those of a polyurethane (PUR) approved for cardiovascular applications. It was found that by embedding PP fibers into the Quatromer matrix, the tensile and fatigue properties of the polymer could be improved, making them comparable, if not better than the PUR. The thrombotic potential of Quatromer was compared with the PUR, glutaraldehyde‐fixed porcine valve material, and a positive and negative control by measuring platelet deposition with radiolabeled platelets in a parallel plate flow configuration. The porcine valve material was found to have significantly higher platelet deposition under all flow regimes, while no significant difference existed between Quatromer and PUR. In conclusion, Quatromer is shown to have suitable hemocompatibility and mechanical durability for use in polymer trileaflet heart valves, and fiber reinforcement can effectively be used to tailor the mechanical properties. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Film from peroxidation of an amino phospholipid and its biocompatibility
Authors: Wang Hua‐Jie , Liu Xin‐Ming , Ji Li‐Wen , Ma Dong‐Lan , Ren Qiushi , Wang Jin‐Ye
Published: April 2006

A new kind of phospholipid product with fluorescence was derived from autoxidation of an aminophospholipid, L‐α‐phosphatidylethanolamine dilinoleoyl in solid film state. Atomic force microscopy showed that the film product was composed of round and elliptical vesicles with diameters of about 20–45 nm. The product was difficult to dissolve in water and most organic solvents. Fourier transform infrared spectroscopy, solid‐state 13C NMR, and solid‐state 31P NMR indicated that the unsaturated double carbon bond decreased with the reaction, and polymerization within/between phospholipid molecules occurred. Endothelial cells from human vein seeded onto the film showed the highest proliferating activity compared with seeding onto Corning culture plate, glass plate, or phospholipid film with phosphorylcholine head group, as evaluated by 3‐(4,5‐timethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide assay (p < 0.001). The hemocompatibility of the film was also assessed by platelet adhesion and protein adsorption. The results suggest that the product has potential applications as a new biomaterial coating. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Diagnostic functional MRI: Illustrated clinical applications and decision‐making
Authors: Bartsch Andreas Joachim , Homola György , Biller Armin , Solymosi László , Bendszus Martin
Published: April 2006

Functional magnetic resonance imaging (fMRI) has become a popular research tool, yet its use for diagnostic purposes and actual treatment planning has remained less widespread. The literature yields rather sparse evidence‐based data on clinical fMRI applications and accordant decision‐making. Notwithstanding, blood oxygenation level dependent (BOLD)‐ and arterial spin labeling (ASL)‐fMRI can be judiciously combined with perfusion measurements, electroencephalographic (EEG) recordings, diffusion‐weighted imaging (DWI), and fiber tractographies to assist clinical decisions. In this article we provide an overview of clinical fMRI applications based on illustrative examples. Assessment of cochlear implant candidates by fMRI is covered in some detail, and distinct reference is made to particular challenges imposed by brain tumors, other space‐occupying lesions, cortical dysplasias, seizure disorders, and vascular malformations. Specific strategies, merits, and pitfalls of analyzing and interpreting diagnostic fMRI studies in individual patients are highlighted. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Report on a multicenter fMRI quality assurance protocol
Authors: Friedman Lee , Glover Gary H.
Published: April 2006

Temporal stability during an fMRI acquisition is very important because the blood oxygen level‐dependent (BOLD) effects of interest are only a few percent in magnitude. Also, studies involving the collection of groups of subjects over time require stable scanner performance over days, weeks, months, and even years. We describe a protocol designed by one of the authors that has been tested for several years within the context of a large, multicenter collaborative fMRI research project (FIRST‐BIRN). A full description of the phantom, the quality assurance (QA) protocol, and the several calculations used to measure performance is provided. The results obtained with this protocol at multiple sites over time are presented. These data can be used as benchmarks for other centers involved in fMRI research. Some issues with the various protocol measures are highlighted and discussed, and possible protocol improvements are also suggested. Overall, we expect that other fMRI centers will find this approach to QA useful and this report may facilitate developing a similar QA protocol locally. Based on the findings reported herein, the authors are convinced that monitoring QA in this way will improve the quality of fMRI data. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Principles of magnetic resonance assessment of brain function
Authors: Norris David G.
Published: April 2006

MRI has advanced to being one of the major tools for the assessment of brain function. This review article examines the basic principles that underpin these measurements. The main emphasis is on the characteristics and detection of blood oxygen level dependent (BOLD) contrast. In the first part of the article the relationship between BOLD, blood flow, blood oxygen, and the rate of metabolic consumption of oxygen is described. The four contrast mechanisms that contribute to the BOLD signal change, namely extravascular static and dynamic dephasing, intravascular T2‐like changes, and the intravascular frequency offset effect are described in terms of their spatial localization and relative contributions to the BOLD signal. The current model of changes in blood flow being an indirect consequence of synaptic input to a region is presented. The second section of the article deals with the imaging characteristics of BOLD in terms of the attainable spatial resolution and linear system characteristics. In the third section, practical BOLD imaging is examined for choice of pulse sequence, resolution, echo time (TE), repetition time (TR), and flip angle. The final section touches on other MRI approaches that are relevant to cognitive neuroimaging, in particular the measurement of blood flow, blood volume, resting state fluctuations in the BOLD signal, and measures of connectivity using diffusion tensor imaging and fiber‐tracking. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Gene‐mediated osteogenic differentiation of stem cells by bone morphogenetic proteins‐2 or ‐6
Authors: Zachos Terri A. , Shields Kathleen M. , Bertone Alicia L.
Published: April 2006

Bone marrow–derived mesenchymal stem cells (BMDMSC) hold promise for targeted osteogenic differentiation and can be augmented by delivery of genes encoding bone morphogenetic proteins (BMP). The feasibility of promoting osteogenic differentiation of BMDMSC was investigated using two BMP genes in monolayer and three‐dimensional alginate culture systems. Cultured BMDMSC were transduced with E1‐deleted adenoviral vectors containing either human BMP2 or BMP6 coding sequence under cytomegalovirus (CMV) promoter control [17:1 multiplicities of infection (moi)] and either sustained in monolayer or suspended in 1 mL 1.2% alginate beads for 22 days. Adenovirus (Ad)‐BMP‐2 and Ad‐BMP‐6 transduction resulted in abundant BMP‐2 and BMP‐6 mRNA and protein expression in monolayer culture and BMP‐2 protein expression in alginate cultures. Ad‐BMP‐2 and Ad‐BMP‐6 transduced BMDMSC in monolayer had earlier and robust alkaline phosphatase‐positive staining and mineralization and were sustained for a longer duration with better morphology scores than untransduced or Ad‐β‐galactosidase‐transduced cells. Ad‐BMP‐2‐ and, to a lesser degree, Ad‐BMP‐6‐transduced BMDMSC suspended in alginate demonstrated greater mineralization than untransduced cells. Gene expression studies at day 2 confirmed an inflammatory response to the gene delivery process with upregulation of interleukin 8 and CXCL2. Upregulation of genes consistent with response to BMP exposure and osteogenic differentiation, specifically endochondral ossification and extracellular matrix proteins, occurred in BMP‐transduced cells. These data support that transduction of BMDMSC with Ad‐BMP‐2 or Ad‐BMP‐6 can accelerate osteogenic differentiation and mineralization of stem cells in culture, including in three‐dimensional culture. BMP‐2–transduced stem cells suspended in alginate culture may be a practical carrier system to support bone formation in vivo. BMP‐6 induced a less robust cellular response than BMP‐2, particularly in alginate culture. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res