bluuebunny/crossref_metadata_2025 huggingface dataset:
Lesões por esforços repetitivos/distúrbios osteomusculares relacionados ao trabalho em cirurgiões-dentistas
Authors: Regis Filho Gilsée Ivan , Michels Glaycon , Sell Ingeborg
Published: January 2007

As patologias denominadas genericamente de Lesões por Esforços Repetitivos (LERs)/Distúrbios Osteomusculares Relacionados ao Trabalho (DORTs), apresentando sinais e sintomas de inflamações dos músculos, tendões, fáscias e nervos dos membros superiores, cintura escapular e pescoço, entre outros, têm chamado a atenção não só pelo aumento da sua incidência mas por existirem evidências de sua associação com o ritmo de trabalho. O exercício profissional obriga que cirurgiões-dentistas utilizem na execução das tarefas os membros superiores e estruturas adjacentes, freqüentemente com repetitividade de um mesmo padrão de movimento, compressão mecânica das estruturas localizadas na região, assumindo posturas incorretas, utilizando força excessiva e ainda, na maioria dos casos, trabalhando sob pressão temporal. O presente estudo utilizou o método epidemiológico transversal para buscar evidências da existência da relação entre as tarefas executadas pelo cirurgião-dentista e as LERs/DORTs. Os estudos empíricos revelaram presença de associação estatisticamente significante entre os dois sexos e as patologias. O sexo feminino apresenta mais lesões que o masculino. Ombro/braço (39,40%), punho/mão (18,30%) e pescoço (17,20%) são as regiões mais afetadas. Finalmente, o presente estudo é mais um indicativo de que as tarefas executadas estão expondo esses profissionais a um risco considerável de adquirir LERs/DORTs.
Desigualdade no tratamento à fratura proximal de fêmur no Rio de Janeiro
Authors: Pinheiro Rejane Sobrino , Travassos Cláudia , Gamerman Dani
Published: January 2007

OBJETIVO: O objetivo deste trabalho é analisar a existência de variações na indicação terapêutica a pacientes com fratura proximal de fêmur entre os hospitais conveniados com o SUS e entre pacientes socialmente distintos. MÉTODO: Foram analisados os dados do SIH-SUS dos hospitais do município do Rio de Janeiro, 1994-1995. RESULTADO: A análise multivariada mostrou que as chances de cirurgia foram maiores para as mulheres (OR=1,53, IC95%1,18-1,99); menores para os hospitais federais (OR = 0,21, IC95% 0,10-0,41), estaduais (OR =0,07, IC95% 0,04-0,12) e municipais (OR=0,11, IC95% 0,07-0,18), em comparação com o hospital privado contratado pelo SUS; foram menores nas emergências (OR=0,31, IC95% 0,19-0,48); e foram maiores nos hospitais localizados em áreas mais privilegiadas (OR=1,68, IC95% 1,52-1,86). CONCLUSÃO: A configuração dos mercados variou com o perfil dos hospitais e pacientes, e a indicação de cirurgia foi associada a fatores não relacionados com a necessidade, mostrando diferenças no acesso ao tratamento adequado.
Uso de testes complementares para avaliação do congelamento do sêmen de bodes submetidos ao manejo de fotoperíodo artificial
Authors: Santos Anselmo Domingos Ferreira , Torres Ciro Alexandre Alves , Fonseca Jeferson Ferreira da , Borges Álan Maia , Guimarães José Domingos , Costa Eduardo Paulino da , Rovay Herbert
Published: January 2007

O congelamento do sêmen de bodes das raças Alpina e Saanen submetidos ao manejo de fotoperíodo artificial foi avaliado por meio dos testes de termorresistência (TTR), hiposmótico (HOST) e de integridade do acrossoma. Foram utilizados oito machos caprinos (quatro da raça Alpina e quatro da raça Saanen) de duas idades diferentes (jovens e adultos). A qualidade do sêmen durante as etapas do congelamento foi superior em bodes jovens de ambas as raças. Avaliada pelo TTR, a motilidade do sêmen fresco apresentou longevidade pós-descongelamento. Os resultados de motilidade espermática, obtidos imediatamente após o descongelamento, tiveram reflexos positivos sobre o TTR, indicando que os sêmens que apresentaram maior motilidade pós-coleta (86,2% vs 79,3%) e pós-descongelamento (37,7% vs 32,0%) tiveram maior longevidade seminal. Os resultados do HOST, tanto para o sêmen fresco quanto para o congelado, não diferiram entre raças e idades. Houve redução na porcentagem de espermatozóides íntegros após o congelamento e descongelamento do sêmen dos animais da raça Alpina e dos adultos Saanen. Houve redução superior a 14% nos valores do HOST para o sêmen congelado em relação aos valores observados para o sêmen fresco (38,0 vs 52,0%, respectivamente). A motilidade espermática progressiva mostrou maior sensibilidade à criopreservação que a integridade da membrana espermática, indicando que a motilidade espermática é mais afetada pelo processo de congelamento que a membrana plasmática. A integridade do acrossoma não foi influenciada pelo descongelamento. Os índices de danos acrossomais (edema, desprendimento parcial e até perda total de acrossoma) mostraram-se dentro do padrão aceitável (44,5%), tanto no pós-descongelamento como após o término do TTR.
Produção de carne de bovinos contemporâneos, machos e fêmeas, terminados em confinamento
Authors: Coutinho Filho José Luiz Viana , Peres Roberto Molinari , Justo Célio Luiz
Published: January 2007

Avaliaram-se os desempenhos produtivo e econômico de bovinos de corte submetidos a dietas para terminação em confinamento. Foram utilizados 28 bovinos jovens da raça Santa Gertrudis, 14 machos não-castrados e 14 fêmeas, distribuídos em um delineamento experimental inteiramente casualizado, em baias individuais. A alimentação foi fornecida de acordo com as exigências para ganho de peso em terminação. As variáveis estudadas foram afetadas pelo sexo. O ganho de peso médio diário foi de 1,80 e 1,22 kg/animal/dia; a conversão alimentar, de 5,61 e 7,18 kg MS/kg de ganho de peso; o rendimento de carcaça, de 55,61 e 52,75%; e a ingestão de MS, de 10,08 e 8,87 kg MS/dia, respectivamente, para machos e fêmeas. A avaliação das carcaças indicou melhor rendimento para os machos, mas as fêmeas foram superiores quanto à porcentagem de traseiro especial e de seus principais cortes comerciais. Na avaliação econômica, o custo com alimentação para produzir uma arroba de carcaça foi de R$ 33,95 para os machos e R$ 37,02 para as fêmeas.
Características da carcaça de cordeiros alimentados com dietas contendo diferentes níveis de fibra em detergente neutro
Authors: Pires Cleber Cassol , Galvani Diego Barcelos , Carvalho Sérgio , Cardoso Adriano Ramos , Gasperin Bernardo Garziera
Published: January 2007

Este estudo foi conduzido com o objetivo de avaliar o efeito de diferentes níveis de FDN na dieta sobre as características de carcaça de cordeiros confinados e abatidos com 30 kg de PV. Foram utilizados 20 cordeiros machos, não-castrados, cruza Ile de France x Texel, distribuídos aleatoriamente em quatro tratamentos (25, 31, 37 e 43% de FDN na dieta). O volumoso utilizado foi silagem de sorgo híbrido (AG 2005 E) e o concentrado foi composto de milho desintegrado, farelo de soja, sal comum, calcário calcítico e fosfato bicálcico. As dietas foram isoprotéicas (17% de PB) e as características avaliadas foram: peso de carcaça quente (PCQ), peso de carcaça fria (PCF), rendimento de carcaça quente (RCQ), rendimento de carcaça fria (RCF), índice de quebra ao resfriamento (IQ), área de olho-de-lombo (AOL), espessura de gordura subcutânea (EG), comprimento da carcaça (CC), largura da perna (LP), profundidade do peito (PPEITO), comprimento de perna (CPERNA), peso e proporção de perna, paleta, costilhar e pescoço e pesos e proporções de osso, músculo e gordura da perna dos cordeiros. O aumento do nível de FDN nas dietas reduziu linearmente o PCQ, PCF, RCQ, RCF e o peso de costilhar. Houve efeito quadrático do nível de FDN sobre o CPERNA. As demais variáveis analisadas não foram influenciadas pelos níveis de FDN das dietas.
Ecoescleroterapia com microespuma em varizes tronculares primárias
Authors: Figueiredo Marcondes , Araújo Salustiano Pereira de , Penha-Silva Nilson
Published: January 2007

OBJETIVO: Avaliar o tratamento de varizes tronculares primárias por ecoescleroterapia com microespuma. MÉTODOS: A amostra foi constituída de 25 membros de seis pacientes do sexo masculino e 19 do sexo feminino, com incompetência das veias safenas magna (21 membros) ou parva (quatro membros). Eles foram avaliados de acordo com a classificação clínica, etiológica, anatômica e fisiopatológica (CEAP) e classificados nos graus C³ (10 membros), C4 (seis membros), C5 (cinco membros) e C6 (quatro membros). A microespuma (5 ml), preparada pela mistura de 1 ml de polidocanol a 3% e 5 ml de ar, era injetada na veia do paciente, em posição de Trendelenburg, com monitoração por ultra-sonografia com Doppler colorido. Os membros eram enfaixados com atadura inelástica por 3 dias; depois disso, os pacientes usavam meias elásticas, 30-40 mmHg, 3/4 ou 7/8, durante 3 meses. A eficiência do tratamento foi avaliada pelo escore clínico da classificação CEAP para dor, edema e claudicação e pelas alterações ultra-sonográficas 12 meses depois. Os escores clínicos antes e depois do tratamento foram comparados pelo teste de Wilcoxon. RESULTADOS: Houve diminuição significante nos escores clínicos (P < 0,05) e sucesso terapêutico, com oclusão total e recanalização parcial sem refluxo, em 84% dos casos. Do total, 16% dos casos apresentaram recanalização parcial, com refluxo, ou recanalização completa. CONCLUSÃO: A ecoescleroterapia, método simples, de baixo custo, que dispensa internação e anestesia, mostrou ser promissora no tratamento de varizes tronculares primárias.
Fluoride intake from drinking water and dentifrice by children living in a tropical area of Brazil
Authors: Omena Leila Maria F. , Silva Milton F. de A. , Pinheiro Cleone Calheiros , Cavalcante Jairo C. , Sampaio Fábio Correia
Published: January 2007

OBJECTIVE: To assess fluoride (F-) intake from water and toothpaste by children aged 18 to 36 months and to monitor the F- concentrations in the drinking water system in a tropical city of Brazil. METHODS: Children (n=58) aged 18-36 months, all lifetime residents of Penedo, state of Alagoas, Brazil, participated in this study. Water F- analyses were carried out in 7 different occasions at least a week apart. For 2 days all the water drunk by each child was accounted for. Fluoride intake from water for each child was estimated using the mean F- concentration of water in 7 different occasions. Fluoride intake from toothpaste was estimated by subtracting the recovered post-brushing F- from the original amount placed in the toothbrush. The F- intake from water and toothpaste was estimated by dividing the total amount of F- ingested by the weight of each child. RESULTS: The mean F- concentration in the drinking water was 0.94 ppm (mean range 0.78-1.1 ppm), which is above the 0.7 ppm recommended for this area of Brazil. Mean total F- intake from water and toothpaste was 0.128 mg F-/Kg Body Weight/day. The daily means of F- intake from water and toothpaste were 0.021 and 0.107 mg F-/Kg Body Weight, respectively. Ninety six percent of children showed F- intake above 0.07 mg F-/Kg Body Weight/day. CONCLUSIONS: Children in Penedo are at risk for developing dental fluorosis due to high F- intake from fluoridated toothpastes. Water fluoridation showed low contribution to the total F- intake. However, high water F- concentrations in the water indicate the need of surveillance of the artificial water fluoridation system.
Minimally Invasive Approaches for Diagnosis and Treatment of Early-Stage Breast Cancer
Authors: Vlastos Georges , Verkooijen Helena M.
Published: January 2007

Learning Objectives

After completing this course, the reader will be able to: Describe the minimally invasive approaches to breast cancer diagnosis and treatment.List the strengths and weaknesses of minimally invasive diagnostic and treatment procedures.Select appropriate patients for minimally invasive approaches to breast cancer diagnosis and treatment.

CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Disseminated Malignancy Misdiagnosed as Thrombotic Thrombocytopenic Purpura: A Report of 10 Patients and a Systematic Review of Published Cases
Authors: Francis Kristin K. , Kalyanam Nalini , Terrell Deirdra R. , Vesely Sara K. , George James N.
Published: January 2007

Learning Objectives

After completing this course, the reader will be able to: List the diagnostic criteria for thrombotic thrombocytopenic purpura.Describe how occult disseminated malignancy can mimic the clinical features of thrombotic thrombocytopenic purpura.Identify the clinical clues that indicate additional diagnostic evaluation for possible malignancy in a patient with suspected thrombotic thrombocytopenic purpura.

CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Cancer Statistics, Trends, and Multiple Primary Cancer Analyses from the Surveillance, Epidemiology, and End Results (SEER) Program
Authors: Hayat Matthew J. , Howlader Nadia , Reichman Marsha E. , Edwards Brenda K.
Published: January 2007

Learning Objectives

After completing this course, the reader will be able to: Discuss the evolving changes in the following cancer-related measures: median age at diagnosis, incidence rate, death rate, lifetime risk, survival, and prevalence.Explain important concepts affecting occurrence of multiple primary cancers at various cancer sites.Describe the impact of the growing and aging population on the future number of cancer cases by age at diagnosis.

CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
The Continuum of Care: A Paradigm for the Management of Metastatic Colorectal Cancer
Authors: Goldberg Richard M. , Rothenberg Mace L. , Van Cutsem Eric , Benson Al B. , Blanke Charles D. , Diasio Robert B. , Grothey Axel , Lenz Heinz-Josef , Meropol Neal J. , Ramanathan Ramesh K. , Becerra Carlos H. Roberto , Wickham Rita , Armstrong Delma , Viele Carol
Published: January 2007

Learning Objectives

After completing this course, the reader should be able to: Discuss recent progress in the treatment of patients with advanced colorectal cancer.Define the continuum-of-care approach and how it may differ from our current approach to the treatment of patients with advanced colorectal cancer.Identify key factors in treatment selection for patients with advanced colorectal cancer.Explain the impact of each active drug in the treatment of advanced colorectal cancer and the impact of treatment with multiple agents over the course of the disease.

CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Increased expression of HSP70 by colon cancer cells is not always associated with access to the dendritic cell cross-presentation pathway
Authors: Matera Lina , Forno Sarah , Galetto Alessandra , Moro Francesco , Garetto Stefano , Mussa Antonio
Published: January 2007

Dendritic cells (DCs) are highly specialized antigen-presenting cells endowed with the unique ability to not only present exogenous antigens upon exposure to MHC II, but also to cross-present these upon exposure to MHC I. This property was exploited to generate the tumor-specific CD8 cytotoxic lymphocyte (CTL) response in DCs-based cancer vaccine protocols. In this context, the source of tumor antigens remains a critical challenge. A crude tumor in the context of danger signals is believed to represent an efficient source of tumor antigens (TAs) for DCs loading. In our previous work, increased DCs cross-presentation of antigens from necrotic gastric carcinoma cells paralleled up-regulation of the heat shock protein hsp70. We studied the expression of hsp70 on primary colon carcinoma cells and its relevance in the cross-priming of anti-tumor CTL by tumor-loaded DCs. Hsp70 was expressed on all three of the tumors studied, but was never detected in the peritumoral normal mucosa (NM). The uptake of the tumor induced a trend towards down-modulation of the monocyte-specific marker CD14, but had no effect on the chemokine receptors CCR4 and CCR7. The IFN-γ enzyme-linked immunospot assay (ELIspot) showed cross-priming of CTL by tumor-loaded but not NM-loaded DCs in four of the six cases studied. The CTL response generated in DC+tumor cultures was directed towards the tumor, but not towards NM, and it was characterized by refractoriness to polyclonal (Ca ionophores, PKC activators) stimuli. Of the three CTL-generating tumors, only one expressed hsp70. This data indicates a tumor-specific expression of hsp70, but does not support its relevance in the DC cross-presentation of TAs.
Reassessment of holoprosencephaly–diencephalic hamartoblastoma (HDH) association
Authors: Castori Marco , Douzgou Sofia , Silvestri Evelina , Encha‐Razavi Férechté , Dallapiccola Bruno
Published: January 2007

We report on a 23‐week fetus with a hypothalamic hamartoma, lobar holoprosencephaly, right anophthalmia, and facial asymmetry, features which are consistent with theholoprosencephaly–diencephalichamartoblastoma (HDH) association. In an attempt to better delineate HDH, we reviewed 19 published patients with similar features. The HDH clinical spectrum ranges from classic holoprosencephaly with micro/anophthalmia, multiple additional findings in non‐contiguous structures and early lethality, to isolated microforms of holoprosencephaly. Associated cephalic features mainly include cortical/neuronal migration defects (39%), meningeal anomalies (28%), brainstem/posterior fossa malformations (22%), dysmorphic ears (41%), facial asymmetry (35%), and hypoplastic mandible (29%). Fifty‐three percent of patients have additional extra‐cephalic malformations, for example, vertebral/rib segmentation defects (50%), hypo/aplastic lungs (38%), congenital heart defect (29%), and urinary anomalies (29%). HDH shows etiological heterogeneity, that is, teratogenic exposure, chromosome imbalances, autosomal recessive as well as dominant “de novo” mutations. Several features could directly result from a disruptive sequence caused by an early hamartoma which alters the development of forebrain, hindbrain, meninges, and 1st–2nd branchial arches, although the pleiotropic action of genetic/environmental factors cannot be excluded. HDH does not emerge as a distinct syndrome, but other hypotheses, including separate conditions within a common pathway and the developmental field defect theory, are discussed. © 2007 Wiley‐Liss, Inc.
Family‐based and case‐control studies reveal no association oflipocalin‐type prostaglandin D2 synthasewith schizophrenia
Authors: Ruano Dina , Macedo António , Soares Maria João , Valente José , Azevedo Maria Helena , Pato Carlos , Hutz Mara Helena , Gama Clarissa S. , Lobato Maria Inês , Belmonte‐de‐Abreu Paulo , Heutink Peter , Palha Joana Almeida
Published: January 2007

Several observations point to the involvement of disturbed lipid biology in schizophrenia. Reduced response to niacin flushing test, which involves vasodilatation induced by prostaglandin D2 (PGD2), is among the evidences, together with decreased CSF levels of lipocalin‐type prostaglandin D2 synthase (PTGDS), the enzyme responsible for the synthesis of PGD2 in the brain. Since PTGDS is also a carrier for lipophilic molecules such as retinoids and thyroid hormones, altered PTGDS levels might influence both PGD2‐mediated signaling, and vitamin A and thyroid hormone availability. To test whether genetic variants ofPTGDSare involved in the etiology of schizophrenia, we searched for variants in the coding and regulatory regions of the gene. We identified four previously described polymorphisms. Using two case‐control samples from Portugal and Brazil, none of the polymorphisms tested was associated with the disease. In addition, no transmission distortion was observed in an independent parents‐offspring sample from the Azorean Islands. Our data do not support the involvement of thePTGDSgene in the etiology of schizophrenia. © 2007 Wiley‐Liss, Inc.
Kling and the “critical”: Social informatics and critical informatics
Authors: Day Ronald E.
Published: January 2007

The article discusses Rob Kling's notion of the critical and how this term is embodied in Kling's social informatics and in works of other authors, which we identify as belonging to critical informatics. Issues of method and the notion of the empirical are discussed. The importance of such analyses in regard to social life and professional education is discussed.
Regulation of male traits by testosterone: implications for the evolution of vertebrate life histories
Authors: Hau Michaela
Published: January 2007

The negative co‐variation of life‐history traits such as fecundity and lifespan across species suggests the existence of ubiquitous trade‐offs. Mechanistically, trade‐offs result from the need to differentially allocate limited resources to traits like reproduction versus self‐maintenance, with selection favoring the evolution of optimal allocation mechanism. Here I discuss the physiological (endocrine) mechanisms that underlie optimal allocation rules and how such rules evolve. The hormone testosterone may mediate life‐history trade‐offs due to its pleiotropic actions in male vertebrates. Conservation in the actions of testosterone in vertebrates has prompted the ‘evolutionary constraint hypothesis,’ which assumes that testosterone signaling mechanisms and male traits evolve as a unit. This hypothesis implies that the actions of testosterone are similar across sexes and species, and only the levels of circulating testosterone concentrations change during evolution. In contrast, the ‘evolutionary potential hypothesis’ proposes that testosterone signaling mechanisms and male traits evolve independently. In the latter scenario, the linkage between hormone and traits itself can be shaped by selection, leading to variation in trade‐off functions. I will review recent case studies supporting the evolutionary potential hypothesis and suggest micro‐evolutionary experiments to unravel the mechanistic basis of life‐history evolution. BioEssays 29: 133–144, 2007. © 2007 Wiley Periodicals, Inc.
DNA barcoding in animal species: progress, potential and pitfalls
Authors: Waugh John
Published: January 2007

Despite 250 years of work in systematics, the majority of species remains to be identified. Rising extinction rates and the need for increased biological monitoring lend urgency to this task. DNA sequencing, with key sequences serving as a “barcode”, has therefore been proposed as a technology that might expedite species identification. In particular, the mitochondrial cytochrome c oxidase subunit 1 gene has been employed as a possible DNA marker for species and a number of studies in a variety of taxa have accordingly been carried out to examine its efficacy. In general, these studies demonstrate that DNA barcoding resolves most species, although some taxa have proved intractable. In some studies, barcoding provided a means of highlighting potential cryptic, synonymous or extinct species as well as matching adults with immature specimens. Higher taxa, however, have not been resolved as accurately as species. Nonetheless, DNA barcoding appears to offer a means of identifying species and may become a standard tool. BioEssays 29: 188–197, 2007. © 2007 Wiley Periodicals, Inc.
Identification of behavioral function in public schools and a clarification of terms
Authors: Kates‐McElrath Kelly , Agnew Maria , Axelrod Saul , Bloh Christopher L.
Published: January 2007

The discipline‐related component of Individuals with Disabilities Education Act (IDEA) requires that schools conduct a Functional Behavioral Assessment (FBA) when a student's behavior disrupts the educational environment and/or results in suspension from school. Applied behavior analysts often make a distinction between the terms functional assessment/functional behavioral assessment, and functional analysis yet there exists no consensus on how that distinction should be made. A relevant review of the literature was conducted to identify research articles using functional analysis or functional assessment methodology in public school settings in an effort to identify the specific procedures employed by each. Results of the review support the existence of a discrepancy between proposed and actual school‐based assessment models, as well as other claims regarding functional assessment research. We address the problem of distinguishing between the terms assessment and analysis as they relate to procedures employed to determine behavioral function of students exhibiting aberrant behavior. A clarification of terms is proposed. Copyright © 2007 John Wiley & Sons, Ltd.
The long term successful treatment of the aggressive/destructive behaviors of a preadolescent with autism
Authors: Foxx Richard M. , Meindl James
Published: January 2007

A program was developed for reducing the aggressive/destructive behavior of a 13‐year‐old boy with autism. All previous interventions had been ineffective. The program included a high density of positive reinforcement, tokens, choice making, response cost, overcorrection, and physical restraint. Treatment occurred in a self‐contained classroom at a school for children with special needs. All of the boy's aggressive/destructive behaviors were reduced to at or near zero levels and these effects have been maintained for over a year. He has made excellent progress in a number of academic areas. Copyright © 2007 John Wiley & Sons, Ltd.
Liquid chromatography–mass spectrometry method for the determination of venlafaxine in human plasma and application to a pharmacokinetic study
Authors: Wei Zhang , Bing‐ren Xiang , Cai‐yun Wang
Published: January 2007

A sensitive and selective liquid chromatographic–mass spectrometric (LC–MS) method for the determination of venlafaxine in human plasma has been developed. Samples were prepared using liquid–liquid extraction and analyzed on a C18 column interfaced with a triple quadrupole mass spectrometer. Positive electrospray ionization was employed as the ionization source. The mobile phase was methanol–water containing 10 mmol/L ammonium acetate, pH 7.9 adjusted with aqueous ammonia (80:20, v/v) at the flow rate of 1.0 mL/min. The analyte and internal standard clozapine were both detected by use of selected ion monitoring mode. The method was linear in the concentration range of 1.0–200.0 ng/mL. The lower limit of quantification (LLOQ) was 1.0 ng/mL. The intra‐ and inter‐day relative standard deviation across three validation runs over the entire concentration range was less than 10.1%. The accuracy determined at three concentrations (5.0, 50.0 and 150.0 ng/mL for venlafaxine) was within ±10.0% in terms of relative error (RE). The method was successfully applied for the evaluation of pharmacokinetic profiles of venlafaxine capsule in 20 healthy volunteers. The results show AUC, Tmax, Cmax and T1/2 between the testing formulation and reference formulation have no significant difference (p > 0.05). Relative bioavailability was 103.4 ± 14.1%. Copyright © 2007 John Wiley & Sons, Ltd.
HPLC method for the determination and pharmacokinetic studies of four triterpenoids in rat plasma after oral administration of Ganoderma lucidum extract
Authors: Wang Xiaoming , Liu Rongxia , Sun Jianghao , Guan Shuhong , Yang Min , Bi Kaishun , Guo Dean
Published: January 2007

Four major triterpenoids (ganoderic acids C2, B, K and H) in rat plasma after oral administration of G. lucidum extract were analyzed quantitatively by high‐performance liquid chromatography (HPLC). Plasma samples taken from rats were acidified with hydrochloric acid and extracted with dichloromethane–ethyl acetate (90:10). The chromatographic separation was achieved on an Agilent Zorbax SB‐C18 column (250 × 4.6 mm, 5 µm) at 35°C, with a linear gradient of acetonitrile and 0.03% aqueous phosphoric acid (v/v), at a flow rate of 1.0 mL/min. The four triterpenoids and internal standard (hydrocortisone) were detected at a wavelength 252 nm. All calibration curves showed good linearity (r2 > 0.99) within test ranges. The relative deviation of this method was less than 10% for intra‐ and inter‐day assays, and the accuracy ranged from 89 to 108%. The extract recovery for the four triterpenoids and internal standard ranged from 95 to 67%, and the QC samples were found to be stable according to the results of the stability study. This is the first report on determination of the major triterpenoids in rat plasma after oral administration of G. lucidum extract and the results provided a firm basis for clarifying the pharmacological effect of G. lucidum and evaluating the clinical applications of this medicinal fungus. Copyright © 2007 John Wiley & Sons, Ltd.
Diurnal rhythm of the chromatin protein Hmgb1 in rat photoreceptors is under circadian regulation
Authors: Hoppe George , Rayborn Mary E. , Sears Jonathan E.
Published: January 2007

Hmgb1 belongs to a family of structure‐specific DNA binding proteins with DNA chaperone‐like properties that mediate chromatin remodeling in a wide range of nuclear processes including regulation of transcription, DNA repair, genome stability, and stress response. A diurnal oscillation of Hmgb1 at the protein level occurs in rat retinal photoreceptor cells and to a lesser extent in bipolar neurons. Expression of Hmgb1 was least at night at Zeitgeber time (ZT) 18 and maximal in the middle of the lights‐on period (ZT6). Since rhythmic expression of Hmgb1 protein in photoreceptors continued in complete darkness, it is likely under control of a circadian clock. Within photoreceptor nuclei, Hmgb1 colocalized with acetylated histone H3, a marker of euchromatin. Outside the nucleus a distinct smaller‐sized isoform of Hmgb1 was present in photoreceptor inner segments and bound to a membrane fraction with characteristics of endoplasmic reticulum membranes. The rhythmic expression of Hmgb1 protein may underlie the circadian change in chromatin remodeling in addition to histone acetylation. J. Comp. Neurol. 501:219–230, 2007. © 2007 Wiley‐Liss, Inc.
Luminescent Eu(III) and Gd(III) Trisbipyridine Cryptates: Experimental and Theoretical Study of the Substituent Effects
Authors: Guillaumont Dominique , Bazin Hervé , Benech Jean‐Marc , Boyer Marion , Mathis Gérard
Published: January 2007

Synthesis, absorption spectra and luminescence properties of a series of lanthanide trisbipyridine cryptates Ln⊂RBpy⋅RBpy⋅RBpy, where Ln=Eu, Gd and R=H, COOH, COOCH3, CONH(CH2)2NH2 are described. Comparison of the unsubstituted parent compound with the substituted compounds shows that bipyridine substitution doesn′t alter significantly the photophysical properties of the lanthanide cryptate. The absorption maximum is slightly red‐shifted when three bipyridines are substituted, whereas substituting one bipyridines has a negligible effect on the absorption spectra. The experimental triplet state energy is between 21 600 and 22 100 cm−1 for the series of compounds and the luminescence lifetimes at 77 K are between 0.5 and 0.8 ms in H2O and equal to 1.7 ms in D2O. The experimental characterizations are completed by DFT and TD‐DFT calculations to assess the ability of these approaches to predict absorption maxima, triplet state energies and structural parameters of lanthanide cryptates and to characterize the electronic structure of the excited states. The calculations on the unsubstituted parent and substituted compounds show that absorption maxima and lowest 3ππ* triplet state energies can be accurately determined from density functional theory (DFT) and time‐dependent (TD) DFT calculations.
Endothelial cells in peripheral blood of healthy subjects and patients with metastatic carcinomas
Authors: Rowand Jason L. , Martin Grace , Doyle Gerald V. , Miller M. Craig , Pierce Michael S. , Connelly Mark C. , Rao Chandra , Terstappen Leon W. M. M.
Published: January 2007

Background:

A lack of standardized assays and consensus of cell definition has lead to a wide variation in the reported range of circulating endothelial cells (CECs).

Methods:

An automated rare cell analysis system was used to enumerate nucleated, CD146+/CD105+/CD45− CECs in 4 mL of blood.

Results:

Recoveries of spiked HUVECs were linear over a range of 0–1,241 cells (R2 ≥ 0.99) with recoveries of ≥70% at each spike level. Correlation coefficient values for interoperator variability and duplicate sample variation were (R2 = 0.99 and 0.90), respectively. Correlation of CEC counts between tubes 1–2 and 2–3 drawn from the same subject in sequence differed (R2 = 0.48 and 0.63, respectively). The normal CEC reference range established in 249 healthy donors was 1–20 CECs/mL blood. CEC counts were significantly higher in the 206 metastatic carcinoma patients (P < 0.0001).

Conclusion:

CECs can be accurately and reproducibly enumerated in blood and are elevated in metastatic carcinomas compared with healthy donors. Phlebotomy procedures can affect endothelial cell counts. © 2007 International Society for Analytical Cytology
Versican proteolysis mediates myocardial regression during outflow tract development
Authors: Kern Christine B. , Norris Russell A. , Thompson Robert P. , Argraves W. Scott , Fairey Sarah E. , Reyes Leticia , Hoffman Stanley , Markwald Roger R. , Mjaatvedt Corey H.
Published: January 2007

An important phase of cardiac outflow tract (OFT) formation is the remodeling of the distal region of the common outlet in which the myocardial sleeve is replaced by with smooth muscle. Here we demonstrate that expression of the proteoglycan versican is reduced before the loss of myocardium from the distal cardiac outlet concomitant with an increase in production of the N‐terminal cleavage fragment of versican. To test whether versican proteolysis plays a role in OFT remodeling, we determined the effects of adenoviral‐mediated expression of a versican isoform devoid of known matrix metalloproteinase cleavage sites (V3) and an N‐terminal fragment of versican (G1). V3 expression promoted an increase in thickness of the proximal OFT myocardial layer independent of proliferation. In contrast, the G1 domain caused thinning and interruptions of the OFT myocardium. These in vivo findings were consistent with findings using cultured primary cardiomyocytes showing that the V3 promoted myocardial cell–cell association while the G1 domain caused a loss of myocardial cell–cell association. Taken together, we conclude that intact versican and G1‐containing versican cleavage products have opposing effects on myocardial cells and that versican proteolysis may facilitate the loss of distal myocardium during OFT remodeling. Developmental Dynamics 236:671–683, 2007. © 2007 Wiley‐Liss, Inc.
A tuberculosis vaccine based on phosphoantigens and fusion proteins induces distinct γδ and αβ T cell responses in primates
Authors: Cendron Delphine , Ingoure Sophie , Martino Angelo , Casetti Rita , Horand Françoise , Romagné François , Sicard Hélène , Fournié Jean‐Jacques , Poccia Fabrizio
Published: January 2007

Phosphoantigens are mycobacterial non‐peptide antigens that might enhance the immunogenicity of current subunit candidate vaccines for tuberculosis. However, their testing requires monkeys, the only animal models suitable for γδ T cell responses to mycobacteria. Thus here, the immunogenicity of 6‐kDa early secretory antigenic target‐mycolyl transferase complex antigen 85B (ESAT‐6‐Ag85B) (H‐1 hybrid) fusion protein associated or not to a synthetic phosphoantigen was compared by a prime‐boost regimen of two groups of eight cynomolgus. Although phosphoantigen activated immediately a strong release of systemic Th1 cytokines (IL‐2, IL‐6, IFN‐γ, TNF‐α), it further anergized blood γδ T lymphocytes selectively. By contrast, the hybrid H‐1 induced only memory αβ T cell responses, regardless of phosphoantigen. These latter essentially comprised cytotoxic T lymphocytes specific for Ag85B (on average + 430 cells/million PBMC) and few IFN‐γ‐secreting cells (+ 40 cells/million PBMC, equally specific for ESAT‐6 and for Ag85B). Hence, in macaques, a prime‐boost with the H‐1/phosphoantigen subunit combination induces two waves of immune responses, successively by γδ T and αβ T lymphocytes.
Aqueous‐Mediated N‐Alkylation of Amines
Authors: Singh Chingakham B. , Kavala Veerababurao , Samal Akshaya K. , Patel Bhisma K.
Published: January 2007

Direct N‐alkylation of primary amines to secondary/tertiary amines and of secondary amines to tertiary amines has been achieved in excellent yields by employing alkyl, benzylic and allylic halides in the presence of NaHCO3 in an aqueous medium at an elevated temperature. Amines of differentstereoelectronic nature react with ease with different halides. The selective formation of secondary amines and the formation of three different substituted tertiary amines are some of the interesting features of this methodology. Reaction in an aqueous medium, operationally convenient conditions, excellent yields and innocuous byproducts, and the absence of transition‐metal catalysts, expensive bases, solid supports and the formation of undesired quaternary ammonium salts makes this method a green chemical process. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Novel Synthesis of Carbamate‐Linked Oligosaccharides by a Modified Curtius Rearrangement
Authors: Sawada Daisuke , Sasayama Shinya , Takahashi Hideyo , Ikegami Shiro
Published: January 2007

We describe a novel stereospecific synthesis of various carbamate‐linked disaccharides using sugar carboxylic acids and sugar alcohols by a modified Curtius rearrangement. Furthermore, we applied this method to the synthesis of carbamate‐linked oligosaccharides including a dendritic molecule. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Composition of the essential oil of Teucrium ramosissimum Desf. (Lamiaceae) from Tunisia
Authors: Hachicha Souleima F. , Skanji Thouraya , Barrek Sami , Ghrabi Zeineb G. , Zarrouk Hédi
Published: January 2007

The essential oil from aerial parts of Teucrium ramosissimum Desf. (Lamiaceae), endemic to North Africa, was isolated by steam distillation and analysed by gas chromatography (GC) and gas chromatography–mass spectrometry (GC–MS). Seventy‐four components were identified; the essential oil was mainly composed of sesquiterpene hydrocarbons and oxygenated sesquiterpenes at nearly the same amounts (41.9% and 42.3%, respectively). δ‐Cadinene (19.97%), α‐cadinol (9.93%) and germacradien‐4‐α‐1‐ol (8.68%) were the major compounds. Copyright © 2007 John Wiley & Sons, Ltd.
Effects of base excision repair gene polymorphisms on pancreatic cancer survival
Authors: Li Donghui , Li Yanan , Jiao Li , Chang David Z. , Beinart Garth , Wolff Robert A. , Evans Douglas B. , Hassan Manal M. , Abbruzzese James L.
Published: January 2007

To explore the association between single nucleotide polymorphisms of DNA repair genes and overall survival of patients with pancreatic cancer, we conducted a study in 378 cases of pancreatic adenocarcinoma who were treated at The University of Texas M. D. Anderson Cancer Center between February 1999 and October 2004 and were followed up to April 2006. Genotypes were determined using genomic DNA and the MassCode method. Overall survival was analyzed using the Kaplan–Meier plot, log‐rank test and Cox regression. We observed a strong effect of the POLB A165G and T2133C genotypes on overall survival. The median survival time (MST) was 35.7 months for patients carrying at least 1 of the 2 homozygous variant POLB GG or CC genotypes, compared with 14.8 months for those carrying the AA/AG or TT/TC genotypes (p = 0.02, log rank test). The homozygous variants of hOGG1 G2657A, APEX1 D148E and XRCC1 R194W polymorphisms all showed a weak but significant effect on overall survival as demonstrated by either log rank test or multivariate COX regression after adjusting for other potential confounders. In combined genotype analysis, a predominant effect of the POLB homozygous variants on survival was observed. When POLB was not included in the model, a slightly better survival was observed among those carrying none of the adverse genotypes than those carrying at least one of the adverse genotypes. These observations suggest that polymorphisms of base excision repair genes significantly affect the clinical outcome of patients with pancreatic cancer. These observations need to be confirmed in a larger study of homogenous patient population. © 2007 Wiley‐Liss, Inc.
Antitumor activity of ALK1 in pancreatic carcinoma cells
Authors: Ungefroren Hendrik , Schniewind Bodo , Groth Stephanie , Chen Wen‐Bin , Müerköster Susanne Sebens , Kalthoff Holger , Fändrich Fred
Published: January 2007

In this study, the authors investigated the expression of activin receptor‐like kinase 1 (ALK1) in pancreatic carcinoma and evaluated its potential role as a tumor suppressor in vitro and in vivo. Endogenous ALK1 expression was demonstrated by immunohistochemistry in both pancreatic tumor tissue and peritumoral normal tissue from 6 patients and by RT‐PCR in 8/12 established pancreatic cancer cell lines. Ectopic expression of a constitutively active (ca) ALK1 mutant in TGF‐β sensitive PANC‐1 and COLO‐357 cells augmented transcriptional activation of a Smad2/3 responsive reporter, and slowed down basal growth in vitro. Both effects were further enhanced by TGF‐β/ALK5 stimulation, suggesting largely independent nuclear Smad signaling by both type I receptors. Upon orthotopic transplantation of PANC‐1‐caALK1 into immunodeficient mice, tumor size was strongly reduced and was associated with a lower microvessel density in the PANC‐1‐caALK1‐derived tumors. In vitro, this mutant efficiently blocked TGF‐β‐induced epithelial‐to‐mesenchymal transdifferentiation and suppressed TGF‐β/ALK5‐mediated activation of the p38 MAPK pathway. Mechanistically, caALK1 silenced MyD118, an immediate TGF‐β target gene whose protein product, GADD45β, couples Smad signaling to p38 activation. These results show that ALK1 activation in pancreatic tumor cells is antioncogenic by inducing ALK5‐independent growth inhibition and by blocking TGF‐β/ALK5‐mediated epithelial‐to‐mesenchymal transdifferentiation and, possibly, invasion and metastatic progression. © 2007 Wiley‐Liss, Inc.
Formation of depurinating N3Adenine and N7Guanine adducts by MCF‐10F cells cultured in the presence of 4‐hydroxyestradiol
Authors: Saeed Muhammad , Rogan Eleanor , Fernandez Sandra V. , Sheriff Fathima , Russo Jose , Cavalieri Ercole
Published: January 2007

Metabolic conversion of endogenous estrogens, estradiol (E2) and estrone (E1), to the catechol estrogens 4‐hydroxyE1(E2) [4‐OHE1(E2)] has been implicated in the initiation of cancer in rodents and humans. Evidence collected in our laboratories has shown that 4‐OHE1(E2) are enzymatically oxidized to E1(E2)‐3,4‐quinones [E1(E2)‐3,4‐Q], which have the potential to damage DNA by forming predominantly depurinating adducts, 4‐OHE1(E2)‐1‐N3Ade and 4‐OHE1(E2)‐1‐N7Gua, leading to the accumulation of mutations and probably cell transformation. The human breast epithelial cell line MCF‐10F has been transformed by treatment with E2or 4‐OHE2. We have used MCF‐10F cells to study the presence of adducts and conjugates after treatment with 4‐OHE2. To mimic the intermittent exposure of breast cells to endogenous estrogens, MCF‐10F cells were treated with 1 μM 4‐OHE2for a 24‐h period at 72, 120, 192 and 240 h postplating. Culture media were collected at each point, extracted by solid‐phase extraction and analyzed by HPLC connected with a multichannel electrochemical detector and/or ultraperformance liquid chromatography/tandem mass spectrometry. Media from successive treatments with 4‐OHE2showed the formation of methoxy and cysteine conjugates, and the depurinating adducts 4‐OHE1(E2)‐1‐N3Ade. The amount of 4‐OHE1(E2)‐1‐N3Ade adducts was higher after the third treatment; smaller amounts of the 4‐OHE1(E2)‐1‐N7Gua adducts were detected after the second and third treatments. These results demonstrate that MCF‐10F cells oxidize 4‐OHE2to E1(E2)‐3,4‐Q, which react with DNA to form the depurinating N3Ade and N7Gua adducts. This DNA damage can play an important role in the 4‐OHE2‐induced mutations and transformation of MCF‐10F cells to malignant cells. © 2007 Wiley‐Liss, Inc.
Multiple histone deacetylases repress tumor suppressor gene ARHI in breast cancer
Authors: Feng Weiwei , Lu Zhen , Luo Robert Z. , Zhang Xiaohong , Seto Edward , Liao Warren S.‐L. , Yu Yinhua
Published: January 2007

ARHI is a maternally imprinted tumor suppressor gene that is expressed in normal breast and ovarian epithelial cells but not in most breast and ovarian cancers. Our earlier studies showed that histone deacetylases (HDACs) in complexes with transcription factors E2F1 and E2F4 play an important role in downregulating ARHI expression in breast cancer cells. To determine which HDAC or HDACs are responsible for repressing ARHI, we cotransfected vectors expressing HDACs 1–11 with an ARHI/luciferase reporter into SKBr3 and MCF‐7 breast cancer cells. Expression of multiple HDACs consistently reduced ARHI promoter activity in a dose‐dependent manner. We also found that the expression level of HDACs 1–3 was higher in breast cancer cell lines than in normal breast epithelial cells. In agreement with their repressive function, depletion of HDACs 1, 3 and 11 not only significantly increased the ARHI promoter activity of the transfected reporter but also activated the transcription of the endogenous ARHI gene. Furthermore, depletion or inhibition of HDACs by small interfering RNA of HDAC11 or by trichostatin A, respectively, increased E2F acetylation. Chromatin immunoprecipitation assays revealed that HDACs 1 and 3 are bound to the ARHI promoter. Taken together, our results suggest that the activity of multiple HDACs contributes to the repression of the ARHI tumor suppressor gene in breast cancer cells. Since HDAC inhibitors are now being used to treat breast cancer, the reactivation of ARHI in these cancer cells may serve as a new biomarker with which to monitor the treatment effects. © 2007 Wiley‐Liss, Inc.
Somatic mutations at the trinucleotide repeats of androgen receptor gene in male hepatocellular carcinoma
Authors: Yeh Shiou‐Hwei , Chiu Chi‐Ming , Chen Chi‐Ling , Lu Shu‐Fen , Hsu Hey‐Chi , Chen Ding‐Shinn , Chen Pei‐Jer
Published: January 2007

Androgen and androgen receptor (AR) have long been implicated in liver carcinogenesis, especially for the male dominance feature. However, whether AR gene could occur in somatic mutations that might contribute to this process has not yet been studied. DNA sequencing and genotyping were conducted for detecting the genetic aberrations of AR gene in 257 primary hepatocellular carcinomas (HCCs) and also the dysplastic nodules (DN) from another 11 patients. Twenty‐one AR somatic mutations causing amino acid changes were identified in HCC and even in the precancerous DN. The missense somatic mutations of AR were rare in HCC (2 cases) but the trinucleotide repeat (TNR) changes, both at (CAG)n and (GGC)n, was a more common one (19 cases). Notably, all these mutations occurred in male patients and most TNR changes belonged to the contraction type (15 out of 19 cases, 78.9%), which has been reported to associate with increased AR transcriptional activity. Most samples with TNR changes did not show microsatellite instability, suggesting a different cause for these TNR mutations. Although no significant correlation was identified between AR mutations and the clinicopathologic parameters, we found the (CAG)n length significantly shorter in hepatitis B virus (HBV)(+) HCCs than in HBV(−) HCCs and the (GGC)n length significantly correlates with the overall survival. In conclusion, the mis‐sense somatic mutations of AR were rare in HCC but the TNR change was a more common one, which exclusively occurred in males. Moreover, the length of TNR carried clinical significance in special HCC group. © 2007 Wiley‐Liss, Inc.