bluuebunny/crossref_metadata_2025 huggingface dataset:
Guidelines on nutritional management in Japanese patients with liver cirrhosis from the perspective of preventing hepatocellular carcinoma
Authors: Suzuki Kazuyuki , Endo Ryujin , Kohgo Yutaka , Ohtake Takaaki , Ueno Yoshiyuki , Kato Akinobu , Suzuki Kazutomo , Shiraki Ryo , Moriwaki Hisataka , Habu Daiki , Saito Masaki , Nishiguchi Shuhei , Katayama Kazuhiro , Sakaida Isao ,   for the Japanese Nutritional Study Group for Liver Cirrhosis 2008
Published: June 2012

Aim:  The Japanese Nutritional Study Group for Liver Cirrhosis (JNUS) was assembled in 2008 with the support of a Health Labor Sciences Research Grant from the Ministry of Health, Labor and Welfare of Japan. The goal of the study group was to propose new nutritional guidelines for Japanese patients with liver cirrhosis (LC), with the aim of preventing hepatocellular carcinoma.

Methods:  Between 2008 and 2010, the member investigators of JNUS conducted various clinical and experimental studies on nutrition on LC. These included anthropometric studies, a questionnaire study on daily nutrient intake, clinical trials, experimental studies using animal models, re‐evaluation of previous publications and patient education. Over this 3‐year period, the group members regularly discussed the nutritional issues related to LC, and a proposal was finally produced.

Results:  Based on the results of JNUS projects and discussions among the members, general recommendations were made on how Japanese patients with LC should be managed nutritionally. These recommendations were proposed with a specific regard to the prevention of hepatocarcinogenesis.

Conclusion:  The new JNUS guidelines on nutritional management for Japanese patients with LC will be useful for the actual nutritional management of patients with LC. The JNUS members hope that these guidelines will form the basis for future discussions and provide some direction in nutritional studies in the field of hepatology.
Utilisation of community pharmacists by the general public in Malaysia
Authors: Chua Siew Siang , Lim Kien Ping , Lee Hong Gee
Published: June 2012

Objectives

The study was conducted to assess how the general public in the Klang Valley, Malaysia, utilised community pharmacists.

Methods

This was a prospective observational study which documented interactions between community pharmacists and their customers. A researcher was stationed in 10 participating community pharmacies around the Klang Valley to observe and record all the interactions, using a structured data-collection form.

Keys findings

Interactions between 1914 customers and the pharmacists of the 10 community pharmacies were recorded. A total of 2199 requests were made by these customers. The main types of request were for medications by brand name (32.2%), advice on minor health problems (25.9%) and for health supplements (11.7%). Only 65 prescriptions were received by the community pharmacies; that is, fewer than two prescriptions per pharmacy per day. The pharmacists provided counselling for only 54.4% of the requests where a medication or health supplement was dispensed. Counselling by pharmacist was significantly associated with the type of request (P < 0.001).

Conclusions

The main reason for the general public to visit a community pharmacy in Malaysia was to purchase a particular medication. Few prescriptions were filled at community pharmacies in Malaysia, indicating the under-utilisation of community pharmacists as a safety net for prescribed medications in primary care.
Blood flow in internal carotid and vertebral arteries during orthostatic stress
Authors: Sato Kohei , Fisher James P. , Seifert Thomas , Overgaard Morten , Secher Niels H. , Ogoh Shigehiko
Published: June 2012

It remains unclear whether orthostatic stress evokes regional differences in cerebral blood flow. The present study compared blood flow in the internal carotid (ICA) and vertebral arteries (VA) during orthostatic stress (60 deg head‐up tilt; HUT) in six healthy young men. The ICA and VA blood flow were measured using Doppler ultrasonography. Dynamic cerebral autoregulation was also determined during supine (Supine) and HUT conditions, from the rate of regulation (RoR) in cerebrovascular conductance of the ICA and VA during acute hypotension induced by the release of bilateral thigh‐cuffs. The HUT decreased ICA blood flow by −9.4 ± 1.7% (P < 0.01 versus Supine), leaving ICA conductance unchanged. In contrast, there was no significant difference in VA blood flow between Supine and HUT, and VA conductance increased (+12.9 ± 0.8%, P < 0.01). In addition, dynamic cerebral autoregulation in both the ICA and VA was attenuated during HUT, and the magnitude of the attenuation in RoR was greater in the VA [0.25 ± 0.03 s−1 Supine versus 0.16 ± 0.02 s−1 HUT (−33.9 ± 5.8%); P < 0.05] compared with the ICA [0.23 ± 0.02 s−1 Supine versus 0.20 ± 0.03 s−1 HUT (−10.6 ± 13.4%); P > 0.05]. These data indicate that orthostatic stress evokes regional differences in cerebral blood flow and possible differences in dynamic cerebral autoregulation between two main brain vascular areas in response to an acute change in blood pressure during orthostatic stress.
Lubricant Effect on the Micro-Tribological Behavior of Magnetic Coating Formulations—Part 2: Comparison of the Results for the Miscellaneous Lubricants
Authors: Farahat Khedr Medhat S.
Published: June 2012

The magnetic tape industry applies a mixture of stearic acid/butylstearate as a lubricant mixture in their formulation. This lubricant system has several disadvantageous points since it enhances corrosion to the GMR head, due to the existence of the stearic acid free carboxylic group; also, it is not chemically bonded to the tape surface and can freely leave the tape surface in time, leading to inferior winding/unwinding performance of the tape. In this work, we pursue our challenging task for finding a better lubricant(s) to resolve the problems with the current commercial lubricant system. We also continue working with the hypothesized model test sample which imitates the features for the real magnetic tape surface. The goal of this series of work is to correlate between the chemical structures for the miscellaneous lubricants and their micro-tribological behavior at the interface between the sample and reference guide surfaces.
Fractal Theory Applied to Evaluate the Tribological Performances of Two Greases Demonstrated in Four-Ball Tests
Authors: Luen Liou Jeng , Hsing Sun Yi , Fin Lin Jen , Chiu Yueh-Ling , Hulang Yih-Chyun
Published: June 2012

In the present study, two commercial greases with different rheological properties were subjected to four-ball tests to identify their performance in anti-wear and anti-scuffing. A wear test machine equipped with a data acquisition system was used to collect and analyze the experimental data of electrical contact resistance (ECR) and friction torque (Tf). Fractal theory was used to deal with the signals of the above two parameters simultaneously. The fractal dimension (Ds) and topothesy (G) of the signals were used to establish their magnitude in relation to the tribological parameters, such as worn surface roughness and friction coefficients. The variations in the fractal parameters can be used to determine the possibility of surface scuffing under the given operating conditions. The frictional energy required for surface scuffing decreases with increasing normal load. Worn surface roughness (Ra) that varies with test time depends strongly on the amount of oxide residual on the worn surface. If the oxide amount increases with time, the surface roughness decreases, which increases the fractal dimension and topothesy of ECR. For grease, the time starting the net growth of oxides is thus the governing factor for variations in worn surface roughness. The fractal dimension of friction coefficients varied in a narrow range regardless of scuffing. However, scuffing in the wear process affected the topothesy of the friction coefficient. The fractal analysis of friction coefficients is an efficient method for determining the possibility of scuffing that arises at contact surfaces during the wear testing processes.
The
lin-4
MicroRNA Targets the LIN-14 Transcription Factor to Inhibit Netrin-Mediated Axon Attraction
Authors: Zou Yan , Chiu Hui , Domenger Dorothée , Chuang Chiou-Fen , Chang Chieh
Published: June 2012

A microRNA instructs neurons when to stop axonal pathfinding.
The Transcription Factor TFEB Links mTORC1 Signaling to Transcriptional Control of Lysosome Homeostasis
Authors: Roczniak-Ferguson Agnes , Petit Constance S. , Froehlich Florian , Qian Sharon , Ky Jennifer , Angarola Brittany , Walther Tobias C. , Ferguson Shawn M.
Published: June 2012

The nuclear translocation of a transcription factor that promotes lysosomal biogenesis is inhibited when lysosomal function is adequate.
Two Gases Required for Vasodilation and Angiogenesis
Authors: Wong Wei
Published: June 2012

Nitric oxide and hydrogen sulfide signaling converge to promote cGMP-dependent processes in endothelial cells.
Pharmacokinetics of Colistin in Cerebrospinal Fluid after Intraventricular Administration of Colistin Methanesulfonate
Authors: Imberti Roberto , Cusato Maria , Accetta Giovanni , Marinò Valeria , Procaccio Francesco , Del Gaudio Alfredo , Iotti Giorgio A. , Regazzi Mario
Published: June 2012

Intraventricular colistin, administered as colistin methanesulfonate (CMS), is the last resource for the treatment of central nervous system infections caused by panresistant Gram-negative bacteria. The doses and daily regimens vary considerably and are empirically chosen; the cerebrospinal fluid (CSF) pharmacokinetics of colistin after intraventricular administration of CMS has never been characterized. Nine patients (aged 18 to 73 years) were treated with intraventricular CMS (daily doses of 2.61 to 10.44 mg). Colistin concentrations were measured using a selective high-performance liquid chromatography (HPLC) assay. The population pharmacokinetics analysis was performed with the P-Pharm program. The pharmacokinetics of colistin could be best described by the one-compartment model. The estimated values (means ± standard deviations) of apparent CSF total clearance (CL/Fm, where Fm is the unknown fraction of CMS converted to colistin) and terminal half-life (
t
1/2λ
) were 0.033 ± 0.014 liter/h and 7.8 ± 3.2 h, respectively, and the average time to the peak concentration was 3.7 ± 0.9 h. A positive correlation between CL/Fm and the amount of CSF drained (range 40 to 300 ml) was observed. When CMS was administered at doses of ≥5.22 mg/day, measured CSF concentrations of colistin were continuously above the MIC of 2 μg/ml, and measured values of trough concentration (
C
trough
) ranged between 2.0 and 9.7 μg/ml. Microbiological cure was observed in 8/9 patients. Intraventricular administration of CMS at doses of ≥5.22 mg per day was appropriate in our patients, but since external CSF efflux is variable and can influence the clearance of colistin and its concentrations in CSF, the daily dose of 10 mg suggested by the Infectious Diseases Society of America may be more prudent.
Examining the Role of Actin-Plasma Membrane Association in Pseudomonas aeruginosa Infection and Type III Secretion Translocation in Migratory T24 Epithelial Cells
Authors: Bridge Dacie R. , Martin Karen H. , Moore Elizabeth R. , Lee Wendy M. , Carroll James A. , Rocha Claudia L. , Olson Joan C.
Published: June 2012

The opportunistic pathogen
Pseudomonas aeruginosa
targets wounded epithelial barriers, but the cellular alteration that increases susceptibility to
P. aeruginosa
infection remains unclear. This study examined how cell migration contributes to the establishment of
P. aeruginosa
infections using (i) highly migratory T24 epithelial cells as a cell culture model, (ii) mutations in the type III secretion (T3S) effector ExoS to manipulate
P. aeruginosa
infection, and (iii) high-resolution immunofluorescent microscopy to monitor ExoS translocation. ExoS includes both GTPase-activating (GAP) and ADP-ribosyltransferase (ADPRT) activities, and
P. aeruginosa
cells expressing wild-type ExoS preferentially bound to the leading edge of T24 cells, where ExoS altered leading-edge architecture and actin anchoring in conjunction with interrupting T3S translocation. Inactivation of ExoS GAP activity allowed
P. aeruginosa
to be internalized and secrete ExoS within T24 cells, but as with wild-type ExoS, translocation was limited in association with disruption of actin anchoring. Inactivation of ExoS ADPRT activity resulted in significantly enhanced T3S translocation by
P. aeruginosa
cells that remained extracellular and in conjunction with maintenance of actin-plasma membrane association. Infection with
P. aeruginosa
expressing ExoS lacking both GAP and ADPRT activities resulted in the highest level of T3S translocation, and this occurred in conjunction with the entry and alignment of
P. aeruginosa
and ExoS along actin filaments. Collectively, in using ExoS mutants to modulate and visualize T3S translocation, we were able to (i) confirm effector secretion by internalized
P. aeruginosa
, (ii) differentiate the mechanisms underlying the effects of ExoS GAP and ADPRT activities on
P. aeruginosa
internalization and T3S translocation, (iii) confirm that ExoS ADPRT activity targeted a cellular substrate that interrupted T3S translocation, (iv) visualize the ability of
P. aeruginosa
and ExoS to align with actin filaments, and (v) demonstrate an association between actin anchoring at the leading edge of T24 cells and the establishment of
P. aeruginosa
infection. Our studies also highlight the contribution of ExoS to the opportunistic nature of
P. aeruginosa
infection through its ability to exert cytotoxic effects that interrupt T3S translocation and
P. aeruginosa
internalization, which in turn limit the
P. aeruginosa
infectious process.
Role of the Agr-Like Quorum-Sensing System in Regulating Toxin Production by Clostridium perfringens Type B Strains CN1793 and CN1795
Authors: Chen Jianming , McClane Bruce A.
Published: June 2012

Clostridium perfringens
type B causes enteritis and enterotoxemia in domestic animals. By definition, these bacteria must produce alpha toxin (CPA), beta toxin (CPB) and epsilon toxin (ETX) although most type B strains also produce perfringolysin O (PFO) and beta2 toxin (CPB2). A recently identified Agr-like quorum-sensing (QS) system in
C. perfringens
controls all toxin production by surveyed type A, C, and D strains, but whether this QS is involved in regulating toxin production by type B strains has not been explored. Therefore, the current study introduced
agrB
null mutations into type B strains CN1795 and CN1793. Both type B
agrB
null mutants exhibited reduced levels of CPB, PFO, and CPA in their culture supernatants, and this effect was reversible by complementation. The reduced presence of CPB in culture supernatant involved decreased
cpb
transcription. In contrast, the
agrB
null mutants of both type B strains retained wild-type production levels of ETX and CPB2. In a Caco-2 cell model of enteritis, culture supernatants of the type B
agrB
null mutants were less cytotoxic than supernatants of their wild-type parents. However, in an MDCK cell
in vitro
model for enterotoxemic effects, supernatants from the
agrB
null mutants or wild-type parents were equally cytotoxic after trypsin activation. Coupling these and previous results, it is now evident that strain-dependent variations exist in Agr-like QS system regulation of
C. perfringens
toxin production. The cell culture results further support a role for trypsin in determining which toxins contribute to disease involving type B strains.
Roles of Inflammatory Caspases during Processing of Zebrafish Interleukin-1β in Francisella noatunensis Infection
Authors: Vojtech Lucia N. , Scharping Nicole , Woodson James C. , Hansen John D.
Published: June 2012

The interleukin-1 family of cytokines are essential for the control of pathogenic microbes but are also responsible for devastating autoimmune pathologies. Consequently, tight regulation of inflammatory processes is essential for maintaining homeostasis. In mammals, interleukin-1 beta (IL-1β) is primarily regulated at two levels, transcription and processing. The main pathway for processing IL-1β is the inflammasome, a multiprotein complex that forms in the cytosol and which results in the activation of inflammatory caspase (caspase 1) and the subsequent cleavage and secretion of active IL-1β. Although zebrafish encode orthologs of IL-1β and inflammatory caspases, the processing of IL-1β by activated caspase(s) has never been examined. Here, we demonstrate that in response to infection with the fish-specific bacterial pathogenFrancisella noatunensis, primary leukocytes from adult zebrafish display caspase-1-like activity that results in IL-1β processing. Addition of caspase 1 or pancaspase inhibitors considerably abrogates IL-1β processing. As in mammals, this processing event is concurrent with the secretion of cleaved IL-1β into the culture medium. Furthermore, two putative zebrafish inflammatory caspase orthologs, caspase A and caspase B, are both able to cleave IL-1β, but with different specificities. These results represent the first demonstration of processing and secretion of zebrafish IL-1β in response to a pathogen, contributing to our understanding of the evolutionary processes governing the regulation of inflammation.
Development of a deletion and genetic linkage map for the 5A and 5B chromosomes of wheat (Triticum aestivum)
Authors: Gadaleta A. , Giancaspro A. , Giove S.L. , Zacheo S. , Incerti O. , Simeone R. , Colasuonno P. , Nigro D. , Valè G. , Cattivelli L. , Stanca M. , Blanco A.
Published: June 2012

The aims of the present study were to provide deletion maps for wheat ( Triticum aestivum L.) chromosomes 5A and 5B and a detailed genetic map of chromosome 5A enriched with popular microsatellite markers, which could be compared with other existing maps and useful for mapping major genes and quantitative traits loci (QTL). Physical mapping of 165 gSSR and EST–SSR markers was conducted by amplifying each primer pair on Chinese Spring, aneuploid lines, and deletion lines for the homoeologous group 5 chromosomes. A recombinant inbred line (RIL) mapping population that is recombinant for only chromosome 5A was obtained by crossing the wheat cultivar Chinese Spring and the disomic substitution line Chinese Spring-5A dicoccoides and was used to develop a genetic linkage map of chromosome 5A. A total of 67 markers were found polymorphic between the parental lines and were mapped in the RIL population. Sixty-three loci and the Q gene were clustered in three linkage groups ordered at a minimum LOD score of 5, while four loci remained unlinked. The whole genetic 5A chromosome map covered 420.2 cM, distributed among three linkage groups of 189.3, 35.4, and 195.5 cM. The EST sequences located on chromosomes 5A and 5B were used for comparative analysis against Brachypodium distachyon (L.) P. Beauv. and rice ( Oryza sativa L.) genomes to resolve orthologous relationships among the genomes of wheat and the two model species.
Bone Mineralization in Celiac Disease
Authors: Larussa Tiziana , Suraci Evelina , Nazionale Immacolata , Abenavoli Ludovico , Imeneo Maria , Luzza Francesco
Published: June 2012

Evidence indicates a well-established relationship between low bone mineral density (BMD) and celiac disease (CD), but data on the pathogenesis of bone derangement in this setting are still inconclusive. In patients with symptomatic CD, low BMD appears to be directly related to the intestinal malabsorption. Adherence to a strict gluten-free diet (GFD) will reverse the histological changes in the intestine and also the biochemical evidence of calcium malabsorption, resulting in rapid increase of BMD. Nevertheless, GFD improves BMD but does not normalize it in all patients, even after the recovery of intestinal mucosa. Other mechanisms of bone injury than calcium and vitamin D malabsorption are thought to be involved, such as proinflammatory cytokines, parathyroid function abnormalities, and misbalanced bone remodeling factors, most of all represented by the receptor activator of nuclear factor B/receptor activator of nuclear factor B-ligand/osteoprotegerin system. By means of dual-energy X-ray absorptiometry (DXA), it is now rapid and easy to obtain semiquantitative values of BMD. However, the question is still open about who and when submit to DXA evaluation in CD, in order to estimate risk of fractures. Furthermore, additional information on the role of nutritional supplements and alternative therapies is needed.
Sensorineural Hearing Loss due to Air Bag Deployment
Authors: Ohki Masafumi , Ishikawa Jyunichi , Tahara Atsushi
Published: June 2012

Deployment of the air bag in a passenger vehicle accident rarely causes otologic injuries. However, sensorineural hearing loss induced by air bag deployment is extremely rare, with only a few cases reported in the English literature. A 38-year-old man involved in a traffic accident while driving his car at 40 km/hour presented with right sensorineural hearing loss and tinnitus, without associated vertigo. Pure-tone audiometry demonstrated elevated thresholds of 30 dB and 25 dB at 4 kHz and 8 kHz, respectively, on the right side. Air bag deployment in car accidents is associated with the risk of development of sensorineural hearing loss.
Factor V-Leiden Mutation: A Common Risk Factor for Venous Thrombosis among Lebanese Patients
Authors: Kreidy Raghid
Published: June 2012

Aim. Lebanon exhibits one of the highest prevalences of factor V-Leiden (FVL) in the world (14.4%). The aim of this study is to evaluate the incidence of FVL mutation among Lebanese patients with lower extremity venous thrombosis.Material and Methods. From January 2003 to January 2011, 283 consecutive Lebanese patients, diagnosed with deep venous thrombosis (DVT) by duplex scan, were retrospectively reviewed. FVL mutation was tested among patients with conditions highly suggestive of hypercoagulation states (65 patients).Results. FVL mutation was detected among 56.9% of patients, 68.6% of patients younger than 50 years, and 43.4% of patients older than 50 years (). FVL mutation was commonly reported in young adults, in patients with pregnancy, estrogen drugs, recurrent DVT, and resistance to anticoagulation.Conclusion. The high rate of FVL mutation observed among Lebanese patients with venous thrombosis is related to the high prevalence of this mutation in the Lebanese population. Thrombophilia screening should be tailored to accommodate a population's risk factor. In countries with high prevalence of FVL, this mutation should be screened among patients younger than 50 years and patients with situations highly suggestive of hypercoagulation states.
Electrochemical Deposition and Formation Mechanism of Single-Crystalline Cu2O Octahedra on Aluminum
Authors: Du Q. T. , Tan J. S. , Wang Q. T. , Li C. Y. , Liu X. H. , Cai R. S. , Ding Y. H. , Wang Y. Q.
Published: June 2012

A simple electrochemical deposition was developed to synthesize the cuprous oxide (Cu2O) octahedra on aluminum foils. The average edge length of the octahedra is about 300 nm. The chemical composition of the octahedra was determined using energy dispersive X-ray spectroscopy and electron energy-loss spectroscopy. The microstructure of the octahedra was investigated using transmission electron microscopy. The formation mechanism of the octahedra is proposed.
Fanconi Anemia Proteins and Their Interacting Partners: A Molecular Puzzle
Authors: Kaddar Tagrid , Carreau Madeleine
Published: June 2012

In recent years, Fanconi anemia (FA) has been the subject of intense investigations, primarily in the DNA repair research field. Many discoveries have led to the notion of a canonical pathway, termed the FA pathway, where all FA proteins function sequentially in different protein complexes to repair DNA cross-link damages. Although a detailed architecture of this DNA cross-link repair pathway is emerging, the question of how a defective DNA cross-link repair process translates into the disease phenotype is unresolved. Other areas of research including oxidative metabolism, cell cycle progression, apoptosis, and transcriptional regulation have been studied in the context of FA, and some of these areas were investigated before the fervent enthusiasm in the DNA repair field. These other molecular mechanisms may also play an important role in the pathogenesis of this disease. In addition, several FA-interacting proteins have been identified with roles in these “other” nonrepair molecular functions. Thus, the goal of this paper is to revisit old ideas and to discuss protein-protein interactions related to other FA-related molecular functions to try to give the reader a wider perspective of the FA molecular puzzle.
Severe Hypothyroidism Causing Pre-Eclampsia-Like Syndrome
Authors: Inversetti Annalisa , Serafini Audrey , Manzoni Marco F. , Dolcetta Capuzzo Anna , Valsecchi Luca , Candiani Massimo
Published: June 2012

Objective.Analyzing and managing pre-eclampsia-like syndrome due to severe hypothyroidism.Methods.Presentation of a case of severe hypothyroidism due to Hashimoto’s syndrome, associated with a severe early-onset preeclampsia-like syndrome, managed in our Gynecology Department.Results.Severe pre-eclampsia led to miscarriage at 24 weeks of gestational age in a 42-year-old woman, although we attempted to correct hypothyroidism with increasing doses of levothyroxine and liothyronine sodium.Conclusion.Recognizing pre-eclampsia-like syndrome caused by overt hypothyroidism from other forms of pregnancy-induced hypertension is essential for choosing the correct treatment.
Advanced Nursing Directives: Integrating Validated Clinical Scoring Systems into Nursing Care in the Pediatric Emergency Department
Authors: deForest Erin Kate , Thompson Graham Cameron
Published: June 2012

In an effort to improve the quality and flow of care provided to children presenting to the emergency department the implementation of nurse-initiated protocols is on the rise. We review the current literature on nurse-initiated protocols, validated emergency department clinical scoring systems, and the merging of the two to create Advanced Nursing Directives (ANDs). The process of developing a clinical pathway for children presenting to our pediatric emergency department (PED) with suspected appendicitis will be used to demonstrate the successful integration of validated clinical scoring systems into practice through the use of Advanced Nursing Directives. Finally, examples of 2 other Advanced Nursing Directives for common clinical PED presentations will be provided.
Potential Inaccuracies in Chloride Measurements in Patients with Severe Metabolic Acidosis
Authors: Makiishi Tetsuya , Nishimura Naomasa , Yoshioka Keiko , Yamamoto Shinya , Mitsuhashi Ryuichi , Maeda Sayako , Konishi Takashi , Hirose Kunihiko
Published: June 2012

Background. To address the cause(s) of the significant differences in chloride (Cl-) concentrations between point-of-care blood gas analyzers and central laboratory analyzers.Methods. Cl-concentrations measured simultaneously by a blood gas analyzer (ABL800 FLEX) and a central laboratory analyzer (Hitachi7600) were collected in patients with severe acidemia (pH<7.20) (n=32) and were examined for correlations between differences in Cl-and factors associated with the acid-base status. Cl-concentrations were measured with both analyzers for samples with different concentrations of lactate, inorganic phosphate, or bicarbonate (HCO3   −).Results. The differences in Cl-concentrations were correlated withHCO3   −concentrations (r=0.72,P<0.0001) and anion gap (r=0.69,P<0.0001). Only the addition ofHCO3   −proportionately increased Cl-levels measured by a Hitachi7600, but it did not affect those measured by an ABL800FLEX.Conclusion. Cl-measurements with some analyzers may be influenced byHCO3   −concentrations, which could result in the observed discrepancies.
A Small-Molecule Inhibitor of Glucose Transporter 1 Downregulates Glycolysis, Induces Cell-Cycle Arrest, and Inhibits Cancer Cell Growth In Vitro and In Vivo
Authors: Liu Yi , Cao Yanyan , Zhang Weihe , Bergmeier Stephen , Qian Yanrong , Akbar Huzoor , Colvin Robert , Ding Juan , Tong Lingying , Wu Shiyong , Hines Jennifer , Chen Xiaozhuo
Published: June 2012

The functional and therapeutic importance of the Warburg effect is increasingly recognized, and glycolysis has become a target of anticancer strategies. We recently reported the identification of a group of novel small compounds that inhibit basal glucose transport and reduce cancer cell growth by a glucose deprivation–like mechanism. We hypothesized that the compounds target Glut1 and are efficacious in vivo as anticancer agents. Here, we report that a novel representative compound WZB117 not only inhibited cell growth in cancer cell lines but also inhibited cancer growth in a nude mouse model. Daily intraperitoneal injection of WZB117 at 10 mg/kg resulted in a more than 70% reduction in the size of human lung cancer of A549 cell origin. Mechanism studies showed that WZB117 inhibited glucose transport in human red blood cells (RBC), which express Glut1 as their sole glucose transporter. Cancer cell treatment with WZB117 led to decreases in levels of Glut1 protein, intracellular ATP, and glycolytic enzymes. All these changes were followed by increase in ATP-sensing enzyme AMP-activated protein kinase (AMPK) and declines in cyclin E2 as well as phosphorylated retinoblastoma, resulting in cell-cycle arrest, senescence, and necrosis. Addition of extracellular ATP rescued compound-treated cancer cells, suggesting that the reduction of intracellular ATP plays an important role in the anticancer mechanism of the molecule. Senescence induction and the essential role of ATP were reported for the first time in Glut1 inhibitor–treated cancer cells. Thus, WZB117 is a prototype for further development of anticancer therapeutics targeting Glut1-mediated glucose transport and glucose metabolism. Mol Cancer Ther; 11(8); 1672–82. ©2012 AACR.
The Your Disease Risk Index for Colorectal Cancer Is an Inaccurate Risk Stratification Tool for Advanced Colorectal Neoplasia at Screening Colonoscopy
Authors: Schroy Paul C. , Coe Alison M. , Mylvaganam Shamini R. , Ahn Lynne B. , Lydotes Maria A. , Robinson Patricia A. , Davis Julie T. , Chen Clara A. , Ashba Jacqueline , Atkinson Michael L. , Colditz Graham A. , Heeren Timothy C.
Published: June 2012

Tailoring the use of screening colonoscopy based on the risk of advanced colorectal neoplasia (ACN) could optimize the cost-effectiveness of colorectal cancer (CRC) screening. Our goal was to assess the accuracy of the Your Disease Risk (YDR) CRC risk index for stratifying average risk patients into low- versus intermediate/high-risk categories for ACN. The YDR risk assessment tool was administered to 3,317 asymptomatic average risk patients 50 to 79 years of age just before their screening colonoscopy. Associations between YDR-derived relative risk (RR) scores and ACN prevalence were examined using logistic regression and χ2 analyses. ACN was defined as a tubular adenoma ≥1 cm, tubulovillous or villous adenoma of any size, and the presence of high-grade dysplasia or cancer. The overall prevalence of ACN was 5.6%. Although YDR-derived RR scores were linearly associated with ACN after adjusting for age and gender (P = 0.033), the index was unable to discriminate “below average” from “above/average” risk patients [OR, 1.01; 95% confidence interval (CI), 0.75–1.37]. Considerable overlap in rates of ACN was also observed between the different YDR risk categories in our age- and gender-stratified analyses. The YDR index lacks accuracy for stratifying average risk patients into low- versus intermediate/high-risk categories for ACN. Cancer Prev Res; 5(8); 1044–52. ©2012 AACR.
Impact of Cilostazol on Restenosis After Percutaneous Coronary Balloon Angioplasty
Authors: Tsuchikane Etsuo , Fukuhara Atsunori , Kobayashi Tohru , Kirino Motohiro , Yamasaki Keita , Kobayashi Tomoko , Izumi Masahiro , Otsuji Satoru , Tateyama Hitone , Sakurai Makoto , Awata Nobuhisa
Published: June 2012

Background
—Restenosis after percutaneous transluminal coronary (balloon) angioplasty (PTCA) remains a major drawback of the procedure. We previously reported that cilostazol, a platelet aggregation inhibitor, inhibited intimal proliferation after directional coronary atherectomy and reduced the restenosis rate in humans. The present study aimed to determine the effect of cilostazol on restenosis after PTCA.

Methods and Results
—Two hundred eleven patients with 273 lesions who underwent successful PTCA were randomly assigned to the cilostazol (200 mg/d) group or the aspirin (250 mg/d) control group. Administration of cilostazol was initiated immediately after PTCA and continued for 3 months of follow-up. Quantitative coronary angiography was performed before PTCA and after PTCA and at follow-up. Reference diameter, minimal lumen diameter, and percent diameter stenosis (DS) were measured by quantitative coronary angiography. Angiographic restenosis was defined as DS at follow-up >50%. Eligible follow-up angiography was performed in 94 patients with 123 lesions in the cilostazol group and in 99 patients with 129 lesions in the control group. The baseline characteristics and results of PTCA showed no significant difference between the 2 groups. However, minimal lumen diameter at follow-up was significantly larger (1.65±0.55 vs 1.37±0.58 mm;
P
<0.0001) and DS was significantly lower (34.1±17.8% vs 45.6±19.3%;
P
<0.0001) in the cilostazol group. Restenosis and target lesion revascularization rates were also significantly lower in the cilostazol group (17.9% vs 39.5%;
P
<0.001 and 11.4% vs 28.7%;
P
<0.001).

Conclusions
—Cilostazol significantly reduces restenosis and target lesion revascularization rates after successful PTCA.
Effect of Hypertension on Mortality in Pima Indians
Authors: Sievers Maurice L. , Bennett Peter H. , Roumain Janine , Nelson Robert G.
Published: June 2012

Background
—The effect of hypertension on mortality was examined in 5284 Pima Indians, 1698 of whom had type 2 diabetes at baseline or developed it during follow-up.

Methods and Results
—During a median follow-up of 12.2 years (range, 0.01 to 24.8 years), 470 nondiabetic subjects and 488 diabetic subjects died. In the nondiabetic subjects, 45 of the deaths were due to cardiovascular disease, 208 to other natural causes, and 217 to external causes; in the diabetic subjects, 106 of the deaths were due to cardiovascular disease, 85 to diabetic nephropathy, 226 to other natural causes, and 71 to external causes. In the nondiabetic subjects, after adjusting for age, sex, body mass index, and serum cholesterol concentration in a proportional hazards model, hypertension predicted death from cardiovascular disease (death rate ratio [DRR]=2.8; 95% CI, 1.4 to 5.6;
P
=0.003). In the diabetic subjects, after additional adjustment for duration of diabetes, plasma glucose concentration, and proteinuria, hypertension strongly predicted deaths from diabetic nephropathy (DRR=3.5; 95% CI, 1.7 to 7.2;
P
<0.001), but it had little effect on deaths from cardiovascular disease (DRR=1.4; 95% CI, 0.88 to 2.3;
P
=0.15).

Conclusions
—We propose that the weak relationship between hypertension and cardiovascular disease in diabetic Pima Indians is not because of a diminished effect of hypertension on cardiovascular disease in diabetes, but because of a relatively greater effect of hypertension on the progression of diabetic nephropathy. Factors that may account for this finding in Pima Indians include a younger age at onset of type 2 diabetes, a low frequency of heavy smoking, favorable lipoprotein profiles and, possibly, enhanced susceptibility to renal disease.
Rapamycin Reverses Chronic Graft Vascular Disease in a Novel Cardiac Allograft Model
Authors: Poston Robert S. , Billingham Margaret , Hoyt E. Grant , Pollard Jeffrey , Shorthouse Randi , Morris Randall E. , Robbins Robert C.
Published: June 2012

Background
—Chronic graft vascular disease (CGVD) in cardiac allografts has been defined as a slowly evolving vasculopathy unresponsive to conventional immunosuppression. We compared 4 rodent models of CGVD to evaluate the reproducibility of CGVD in heart allografts. Rapamycin (Rapa) and cyclosporine (CSA) were then used to treat CGVD.

Methods and Results
—Hearts were harvested and placed heterotopically into allogenic recipients. CGVD scores of PVG allografts from ACI recipients treated with CSA on days 1 through 10 were significantly elevated on day 90 (n=16) compared with other models (immunosuppression used): (1) Lewis to F344 recipients (CSA), (2) Brown Norway to Lewis (FK506), and (3) DA to Wistar-Firth (methylprednisolone, azathioprine, CSA). Although delayed (day 60 to 90) CSA treatment had no effect (n=6), delayed Rapa (3 mg · kg
−1
· d
−1
IP) reversed CGVD in PVG grafts (0.22±0.19 on day 90, n=6). ACI isografts showed no evidence of CGVD (n=6) at day 90. Immunohistochemistry of PVG grafts revealed perivascular infiltrates consisting of CD4
+
T cells and limited numbers of macrophages persisting up to day 90. Flow cytometry demonstrated increased levels of anti-donor antibody at day 90, which was significantly inhibited by Rapa treatment.

Conclusions
—PVG grafts developed a significant increase in CGVD without evidence of ongoing myocardial rejection. This CGVD appeared to be mediated by both cellular and humoral mechanisms, given CD4
+
perivascular infiltrates and increased levels of anti-donor antibody. The anti-CGVD effectiveness of Rapa during a period in which there was little myocardial cellular infiltrate supports a novel mechanism of effect such as smooth muscle or B-cell inhibition.
Comparison of Candesartan, Enalapril, and Their Combination in Congestive Heart Failure
Authors: McKelvie R. S. , Yusuf S. , Pericak D. , Avezum A. , Burns R. J. , Probstfield J. , Tsuyuki R. T. , White M. , Rouleau J. , Latini R. , Maggioni A. , Young J. , Pogue J.
Published: June 2012

Background
—We investigated the effects of candesartan (an angiotensin II antagonist) alone, enalapril alone, and their combination on exercise tolerance, ventricular function, quality of life (QOL), neurohormone levels, and tolerability in congestive heart failure (CHF).

Methods and Results
—Seven hundred sixty-eight patients in New York Heart Association functional class (NYHA-FC) II to IV with ejection fraction (EF) <0.40 and a 6-minute walk distance (6MWD) <500 m received either candesartan (4, 8, or 16 mg), candesartan (4 or 8 mg) plus 20 mg of enalapril, or 20 mg of enalapril for 43 weeks. There were no differences among groups with regard to 6MWD, NYHA-FC, or QOL. EF increased (
P
=NS) more with candesartan-plus-enalapril therapy (0.025±0.004) than with candesartan alone (0.015±0.004) or enalapril alone(0.015±0.005). End-diastolic (EDV) and end-systolic (ESV) volumes increased less with combination therapy (EDV 8±4 mL; ESV 1±4 mL;
P
<0.01) than with candesartan alone (EDV 27±4 mL; ESV 18±3 mL) or enalapril alone (EDV 23±7 mL; ESV 14±6 mL). Blood pressure decreased with combination therapy (6±1/4±1 mm Hg) compared with candesartan or enalapril alone (
P
<0.05). Aldosterone decreased (
P
<0.05) with combination therapy (23.2±5.3 pg/mL) at 17 but not 43 weeks compared with candesartan (0.7±7.8 pg/mL) or enalapril (−0.8±11.3 pg/mL). Brain natriuretic peptide decreased with combination therapy (5.8±2.7 pmol/L;
P
<0.01) compared with candesartan (4.4±3.8 pmol/L) and enalapril alone (4.0±5.0 pmol/L).

Conclusions
—Candesartan alone was as effective, safe, and tolerable as enalapril. The combination of candesartan and enalapril was more beneficial for preventing left ventricular remodeling than either candesartan or enalapril alone.
Aerobic Exercise Training Can Reverse Age-Related Peripheral Circulatory Changes in Healthy Older Men
Authors: Beere Polly A. , Russell Stuart D. , Morey Miriam C. , Kitzman Dalane W. , Higginbotham Michael B.
Published: June 2012

Background
—The age-related decline in maximal oxygen consumption is attenuated by habitual aerobic exercise. However, the relative effects of training on central and peripheral responses to exercise in older subjects are not known. The present study assessed the contribution of central and peripheral responses to the age-associated decline in peak oxygen consumption and compared the effect of exercise training in healthy older and younger subjects.

Methods and Results
—Ten older and 13 younger men underwent invasive measurement of central and peripheral cardiovascular responses during an upright, staged cycle exercise test before and after a 3-month period of exercise training with cycle ergometry. At baseline, cardiac output and AV oxygen difference during exercise were significantly lower in older subjects. With training, the older and younger groups increased maximal oxygen consumption by 17.8% and 20.2%, respectively. Peak cardiac output was unchanged in both groups. Systemic AV oxygen difference increased 14.4% in the older group and 14.3% in the younger group and accounted for changes in peak oxygen consumption. Peak leg blood flow increased by 50% in older subjects, whereas the younger group showed no significant change. There was no change in peak leg oxygen extraction in the older group, but in the younger group, leg AV oxygen difference increased by 15.4%.

Conclusions
—These findings suggest that the age-related decline in maximal oxygen consumption results from a reversible deconditioning effect on the distribution of cardiac output to exercising muscle and an age-related reduction in cardiac output reserve.
Alcohol Consumption and Stroke Incidence in Male Smokers
Authors: Leppälä Jaana M. , Paunio Mikko , Virtamo Jarmo , Fogelholm Rainer , Albanes Demetrius , Taylor Philip R. , Heinonen Olli P.
Published: June 2012

Background
—Studies on alcohol consumption and incidences of stroke subtypes have suggested distinct dose-response relationships. Blood pressure and HDL cholesterol mediate the effect of alcohol on coronary heart disease, but similar evidence on cerebrovascular diseases is not available.

Methods and Results
—We studied the risk of stroke in 26 556 male cigarette smokers 50 to 69 years of age without history of stroke. The men were categorized as nondrinkers, light (≤24 g/d), moderate (25 to 60 g/d), or heavy (>60 g/d) drinkers. A total of 960 men suffered from incident stroke: 83 with subarachnoid and 95 with intracerebral hemorrhage, 733 with cerebral infarction, and 49 with unspecified stroke. The adjusted relative risk of subarachnoid hemorrhage was 1.0 in light drinkers, 1.3 in moderate drinkers, and 1.6 in heavy drinkers compared with nondrinkers. The respective relative risks of intracerebral hemorrhage were 0.8, 0.6, and 1.8; of cerebral infarction, 0.9, 1.2, and 1.5. Systolic blood pressure attenuated the effect of alcohol consumption in all subtypes of stroke, whereas HDL cholesterol strengthened the effect of alcohol in subarachnoid hemorrhage and cerebral infarction but attenuated the effect in intracerebral hemorrhage.

Conclusions
—Alcohol consumption may have a distinct dose-response relationship within each stroke subtype—linear in subarachnoid hemorrhage, U-shaped in intracerebral hemorrhage, and J-shaped in cerebral infarction—but further studies are warranted. Systolic blood pressure and HDL cholesterol seem to mediate the effect of alcohol on stroke incidence, but evidently additional mechanisms are involved.
Dietary Lipid Lowering Reduces Tissue Factor Expression in Rabbit Atheroma
Authors: Aikawa Masanori , Voglic Sami J. , Sugiyama Seigo , Rabkin Elena , Taubman Mark B. , Fallon John T. , Libby Peter
Published: June 2012

Background
—The mechanisms by which lipid lowering reduces the incidence of acute thrombotic complications of coronary atheroma in clinical trials remains unknown. Tissue factor (TF) overexpressed in atheroma may accelerate thrombus formation at the sites of plaque disruption. A cell surface cytokine CD40 ligand (CD40L) enhances TF expression in vitro.

Methods and Results
—To test the hypothesis that lipid lowering reduces TF expression and activity, we produced atheroma in rabbit aortas by balloon injury and cholesterol feeding for 4 months (Baseline group, n=15), followed by either a chow diet (Low group, n=10) or a continued high-cholesterol diet for 16 months (High group, n=5). Immunolocalization of TF, CD40L, and its receptor CD40 was quantified by computer-assisted color image analysis. Macrophages in atheroma of the Baseline and High groups strongly expressed TF. Intimal smooth muscle cells and endothelial cells also contained immunoreactive TF. Regions of expression of CD40L and CD40 colocalized with TF. Protein expression of TF diminished substantially in the Low group in association with reduced expression of CD40L and CD40. In situ binding of TF to factors VIIa and X, detected by digoxigenin-labeled factors VIIa and X, colocalized with TF protein in atheroma and decreased after lipid lowering. We also determined reduced TF biological activity in the Low group by use of a chromogenic assay. The level of TF mRNA detected by reverse transcription–polymerase chain reaction also decreased after lipid lowering.

Conclusions
—These results suggest decreased expression and activity of TF as a novel mechanism of reduced incidence of thrombotic complications of atherosclerosis by lipid lowering.
Circulating Levels of Secretory Type II Phospholipase A
2
Predict Coronary Events in Patients with Coronary Artery Disease
Authors: Kugiyama Kiyotaka , Ota Yasutaka , Takazoe Keiji , Moriyama Yasushi , Kawano Hiroaki , Miyao Yuji , Sakamoto Tomohiro , Soejima Hirofumi , Ogawa Hisao , Doi Hideki , Sugiyama Seigo , Yasue Hirofumi
Published: June 2012

Background
—The circulating levels of secretory nonpancreatic type II phospholipase A
2
(sPLA
2
) are increased in various chronic inflammatory diseases and the increase in the levels correlates with the disease severity. sPLA
2
may possibly play a role in atherogenesis and is highly expressed in atherosclerotic arterial walls that are known to have inflammatory features. Thus, this study prospectively examined whether circulating levels of sPLA
2
may have a significant risk and prognostic values in patients with coronary artery disease (CAD).

Methods and Results
—Plasma levels of sPLA
2
were measured in 142 patients with CAD and in 93 control subjects by a radioimmunoassay. The sPLA
2
levels had a significant and positive relations with serum levels of C-reactive protein, a marker of systemic inflammation, and with the number of the traditional coronary risk factors associated with individuals. Multivariate logistic regression analysis showed that higher levels of sPLA
2
(>246 ng/dL; 75th percentile of sPLA
2
distribution in controls) were a significant and independent risk factor for the presence of CAD. In multivariate Cox hazard analysis, the higher levels of sPLA
2
were a significant predictor of developing coronary events (ie, coronary revascularization, myocardial infarction, coronary death) during a 2-year follow-up period in patients with CAD independent of other risk factors, including CRP levels, an established inflammatory predictor.

Conclusions
—The increase in circulating levels of sPLA
2
is a significant risk factor for the presence of CAD and predicts clinical coronary events independent of other risk factors in patients with CAD; these results may reflect possible relation of sPLA
2
levels with inflammatory activity in atherosclerotic arteries.