bluuebunny/crossref_metadata_2025 huggingface dataset:
Decreased transfusion needs associated with hydroxyurea therapy in Algerian patients with thalassemia major or intermedia
Authors: Bradai Mohamed , Pissard Serge , Abad Mohand Tayeb , Dechartres Agnes , Ribeil Jean‐Antoine , Landais Paul , De Montalembert Mariane
Published: July 2007

BACKGROUND: Studies of evolution of transfusion requirements in thalassemic patients treated with hydroxyurea have produced somewhat conflicting results, especially in patients with thalassemia major. Our aims were to determine the proportion of good responders to hydroxyurea in a population of transfusion‐dependent thalassemic patients and to identify the factors associated with a decrease of transfusion needs.

STUDY DESIGN AND METHODS: Hydroxyurea treatment was initiated in 9 patients with thalassemia intermedia (TI) and 45 with thalassemia major (TM). Patients received transfusions when their hemoglobin (Hb) levels dropped below 6 g per dL. A decrease in annual transfusion requirements greater than 70 percent defined a good response, between 40 and 70 percent a partial response, and smaller than 40 percent no response.

RESULTS: The response was good in 8 (90%) patients with TI and 20 (44.5%) with TM, partial in 9 (20%) patients with TM, and absent in 1 (10%) with TI and 16 (35.5%) with TM. In TM patients, transfusion needs decreased by 56 percent over the first year of hydroxyurea treatment. By univariate analysis, a better response to hydroxyurea was associated with older age at the first transfusion (p = 0.02), higher prehydroxyurea Hb (p = 0.0004), codon 6(–A) mutation (p = 0.002), TI (p = 0.03), and history of splenectomy (p = 0.05). Xmn1–/– was associated with a worse response (p = 0.0001). By multivariate analysis, a better response was associated with the Xmn1 polymorphism (p = 0.008).

CONCLUSION: Hydroxyurea may be an alternative to transfusions for TI patients as well as for TM patients in countries that have limited blood supplies.
Intravenous immunoglobulin utilization in the Canadian Atlantic provinces: a report of the Atlantic Collaborative Intravenous Immune Globulin Utilization Working Group
Authors: Constantine Maggie M. , Thomas Wanda , Whitman Lucinda , Kahwash Eiad , Dolan Sean , Smith Susan , Caudle Christopher J. , Burton Erica , Anderson David R.
Published: July 2007

BACKGROUND: Intravenous immunoglobulin (IVIG) use for labeled and unlabeled indications is growing steadily. By use of a collaborative regional strategy, baseline IVIG usage and appropriateness of utilization were determined for Atlantic Canada. The effectiveness of strategies designed to optimize utilization was also studied.

STUDY DESIGN AND METHODS: A regional working group was created to monitor IVIG utilization for a 2‐year period in the four Canadian Atlantic Provinces. A registry of IVIG was created. Assessment of indication appropriateness was determined with national and provincial guidelines along with expert clinical opinion. To optimize IVIG use, IVIG guidelines and feedback reports were distributed to stakeholders. Appropriateness of IVIG use was compared over the course of the study.

RESULTS: The leading indications for IVIG use were idiopathic thrombocytopenic purpura (17.3%), primary immune deficiency conditions (14.9%), and chronic idiopathic demyelinating polyneuropathy (11.8%). The leading prescribing specialists were neurologists (32.2%) and hematologists (26.1%). A total of 37.1 percent of IVIG usage was in accordance with labeled indications. After optimization strategies were implemented, there was little change in labeled use. There was a 4.2 percent decrease in unlabeled use not supported by evidence (p < 0.001).

CONCLUSIONS: A regional collaborative strategy for monitoring IVIG use was established. Most of the IVIG use was for labeled or appropriate indications. The majority of unlabeled use was supported by the medical literature. Strategies to optimize IVIG utilization were associated with a decrease in inappropriate IVIG use and a plateau in IVIG utilization compared to the rest of the country.
Single‐Center Randomized Evaluation of Paclitaxel‐Eluting Versus Conventional Stent in Acute Myocardial Infarction (SELECTION)
Authors: CHECHI TANIA , VITTORI GUIDO , BIONDI ZOCCAI GIUSEPPE G.L. , VECCHIO SABINE , FALCHETTI ELENA , SPAZIANI GAIA , BALDERESCHI GIORGIO , GIGLIOLI CRISTINA , VALENTE SERAFINA , MARGHERI MASSIMO
Published: July 2007

Objectives:

To evaluate the superiority of the paclitaxel‐eluting stent (PES) in reducing neointimal hyperplasia (NIH) over its corresponding bare metal stent (BMS) during primary percutaneous coronary intervention (PCI).

Background:

Primary PCI with stent implantation is the repercussion strategy of choice for ST‐elevation myocardial infarction (STEMI); nonetheless restenosis rate is still high. Drug‐eluting stents have been proven to reduce restenosis rate in many settings, but their use during primary PCI is still controversial.

Methods:

Consecutive patients with STEMI <12 hours were randomized to receive PES or BMS. The primary end‐point was the percentage of the stent volume obstructed by neointimal proliferation (NIH) measured by intravascular ultrasound (IVUS) at a 7‐month angiographic follow‐up. Secondary end‐points were binary restenosis rate and major adverse cardiac events (MACE, i.e., death, nonfatal myocardial infarction, and target lesion revascularization).

Results:

Eighty patients with STEMI were randomized into the PES or BMS group. Patients were well matched for baseline characteristics and the index procedure was always successful. In‐hospital and 1‐month MACE were 2.5% per group. NIH at 7 months was 4.6% versus 20% (P< 0.01), late lumen loss 0.1 versus 1.01 mm (P = 0.01). MACE were 7.5% versus 42.5% (P = 0.001) with no difference in death and recurrent myocardial infarction rates. Late‐acquired incomplete stent apposition (ISA) rate was 5.1% versus 2.7% (P = 0.65). One subacute stent thrombosis was reported in each group.

Conclusions:

PES was superior to its corresponding BMS in reducing NIH in the STEMI setting without any increase in early and long‐term clinical adverse events.
Melatonin increases cleavage rate of porcine preimplantation embryos in vitro
Authors: Rodriguez‐Osorio N. , Kim I. J. , Wang H. , Kaya A. , Memili E.
Published: July 2007

Abstract:  Melatonin has been used to promote in vitro embryo development in different species. This study determined the effects of melatonin on in vitro porcine embryo development; in particular, cleavage rate, blastocyst rate, and blastocyst cell number. Starting 5 hr after insemination, porcine zygotes were cultured in porcine zygote medium 3 (PZM‐3) culture medium supplemented with melatonin at increasing concentrations (10−12 m, 10−9 m, 10−6 m, 10−3 m). Melatonin at a concentration of 10−9 m had a positive effect on cleavage rates, while the highest concentration of melatonin (10−3 m) significantly decreased cleavage rates. Although blastocyst rates were not increased by 10−9 m melatonin, blastocyst cell numbers were significantly higher for embryos subjected to 10−9 m melatonin. The expression levels of the pro‐apoptotic gene BAX and anti‐apoptotic gene BCL2L1 in blastocysts were not affected by the presence of melatonin in the culture medium. To further study the protective properties of 10−9 m melatonin against stressful conditions, hydrogen peroxide (0.01 mm) and heat (40°C) were used during embryo culture. The addition of melatonin to embryos subjected to 40°C for 3 hr increased cleavage rates, but had no protective effect for embryos subjected to 0.01 mm H2O2, probably because the physiological levels of melatonin could not counteract the pharmacological levels of H2O2. Our data indicate that 10−9 m melatonin has a positive effect on porcine embryo cleavage rates and blastocyst total cell numbers and it might have a protective effect against heat stress.
PTCH germline mutations in Chinese nevoid basal cell carcinoma syndrome patients
Authors: Li T‐J , Yuan J‐W , Gu X‐M , Sun L‐S , Zhao H‐S
Published: July 2007

Objectives:  PTCH, the human homologue of the Drosophila segment polarity gene, patched, has been identified as the gene responsible for nevoid basal cell carcinoma syndrome. The aim of this study was to investigate PTCH gene mutation in Chinese patients with nevoid basal cell carcinoma syndrome.

Materials and methods:  DNA was isolated from both odontogenic keratocyst tissue and peripheral blood of five patients with syndrome and one patient with only multiple odontogenic keratocysts, and mutational analysis of the PTCH gene performed by direct sequencing after amplification of all 23 exons by polymerase chain reaction (PCR).

Results:  A previously reported germline mutation (c.2619C>A) was identified in two familial cases involving the mother and the daughter, with the mother also carrying a novel somatic mutation (c.361_362insGAGC). Three novel germline PTCH mutations (c.1338_1339insGCG, c.331delG and c.1939A>T) were detected in three unrelated patients with syndrome. The patient with multiple odontogenic keratocysts who failed to fulfill the diagnostic criteria of the syndrome also carried a novel germline mutation (c.317T>G).

Conclusion:  The frequent germline PTCH mutations detected in our series provide further evidence for the crucial role of PTCH in the pathogenesis of nevoid basal cell carcinoma syndrome in Chinese.
Structure–activity and High‐content Imaging Analyses of Novel Tubulysins
Authors: Wang Zhiyong , McPherson Peter A. , Raccor Brianne S. , Balachandran Raghavan , Zhu Guangyu , Day Billy W. , Vogt Andreas , Wipf Peter
Published: July 2007

The synthesis and biological evaluation of three tubulysin analogs provides the first structure–activity relationship in this family of potent cytotoxic myxobacteria metabolites. Most importantly, the labile N,O‐acetal at N14 is not essential for biological activity. Further, structural simplifications are possible without abolishing biological activities. The N‐terminal amino acid can be replaced with N‐methylsarcosine, and the configuration at the acetoxy‐bearing stereocenter at C11 is important but not critical for almost all aspects of the biological profile. Our data encourage further development of these compounds as potential therapeutic agents in cancer treatment.
Preparation of CIGSS Thin-Film Solar Cells by Rapid Thermal Processing
Authors: Kulkarni Sachin S. , Shirolikar Jyoti S. , Dhere Neelkanth G.
Published: July 2007

Rapid thermal processing (RTP) provides a way to rapidly heat substrates to an elevated temperature to perform relatively short duration processes, typically less than 2–3min long. RTP can be utilized to minimize the process cycle time without compromising process uniformity, thus eliminating a bottleneck in CuIn1−xGaxSe2−ySy (CIGSS) module fabrication. Some approaches have been able to realize solar cells with conversion efficiencies close or equal to those for conventionally processed solar cells with similar device structures. A RTP reactor for preparation of CIGSS thin films on 10cm×10cm substrates has been designed, assembled, and tested at the Florida Solar Energy Center’s PV Materials Lab. This paper describes the synthesis and characterization of CIGSS thin-film solar cells by the RTP technique. Materials characterization of these films was done by scanning electron microscopy, x-ray energy dispersive spectroscopy, x-ray diffraction, Auger electron spectroscopy, electron probe microanalysis, and electrical characterization was done by current–voltage measurements on soda lime glass substrates by the RTP technique. Encouraging results were obtained during the first few experimental sets, demonstrating that reasonable solar cell efficiencies (up to 9%) can be achieved with relatively shorter cycle times, lower thermal budgets, and without using toxic gases.
Design and Performance of a Prototype Thermophotovoltaic System
Authors: Astle Chris J. , Kovacik Gary J. , Heidrick Ted R.
Published: July 2007

A prototype thermophotovoltaic (TPV) system, utilizing a cylindrical radiant burner, and GaSb cells, was assembled and tested. A unique combination of nine-layer dielectric and quartz-214 optical filtering components was utilized to minimize circuit heating, and increase emitter temperature. An evaluation of the performance of each of the spectral filtering components, and a mapping of energy losses throughout the system are provided for burner firing rates ranging from 6kW to 9kW. Fuel to electric conversion efficiency for this prototype TPV system was found to increase linearly from 1.2% at 6kW to 1.5% at 9kW. This corresponded to power densities ranging from 0.07W∕cm2 at 6kW to 0.13W∕cm2 at 9kW Areas that require additional improvement in order to increase system efficiency are addressed.
Common Sequence Polymorphisms Shaping Genetic Diversity inArabidopsis thaliana
Authors: Clark Richard M. , Schweikert Gabriele , Toomajian Christopher , Ossowski Stephan , Zeller Georg , Shinn Paul , Warthmann Norman , Hu Tina T. , Fu Glenn , Hinds David A. , Chen Huaming , Frazer Kelly A. , Huson Daniel H. , Schölkopf Bernhard , Nordborg Magnus , Rätsch Gunnar , Ecker Joseph R. , Weigel Detlef
Published: July 2007

The genomes of individuals from the same species vary in sequence as a result of different evolutionary processes. To examine the patterns of, and the forces shaping, sequence variation inArabidopsis thaliana, we performed high-density array resequencing of 20 diverse strains (accessions). More than 1 million nonredundant single-nucleotide polymorphisms (SNPs) were identified at moderate false discovery rates (FDRs), and ∼4% of the genome was identified as being highly dissimilar or deleted relative to the reference genome sequence. Patterns of polymorphism are highly nonrandom among gene families, with genes mediating interaction with the biotic environment having exceptional polymorphism levels. At the chromosomal scale, regional variation in polymorphism was readily apparent. A scan for recent selective sweeps revealed several candidate regions, including a notable example in which almost all variation was removed in a 500-kilobase window. Analyzing the polymorphisms we describe in larger sets of accessions will enable a detailed understanding of forces shaping population-wide sequence variation inA. thaliana.
Response to Comment on "Redefining the Age of Clovis: Implications for the Peopling of the Americas"
Authors: Waters Michael R. , Stafford Thomas W.
Published: July 2007

Haynes
et al
. misrepresent several aspects of our study. Our revised dates and other archaeological data imply that Clovis does not represent the earliest occupation of the Americas, and we offered both human migration and technology diffusion as hypotheses to explain the expansion of Clovis. We stand by the data and conclusions presented in our original report.
Genetic Diversity in Honey Bee Colonies Enhances Productivity and Fitness
Authors: Mattila Heather R. , Seeley Thomas D.
Published: July 2007

Honey bee queens mate with many males, creating numerous patrilines within colonies that are genetically distinct. The effects of genetic diversity on colony productivity and long-term fitness are unknown. We show that swarms from genetically diverse colonies (15 patrilines per colony) founded new colonies faster than swarms from genetically uniform colonies (1 patriline per colony). Accumulated differences in foraging rates, food storage, and population growth led to impressive boosts in the fitness (i.e., drone production and winter survival) of genetically diverse colonies. These results further our understanding of the origins of polyandry in honey bees and its benefits for colony performance.
Intra- and Intermolecular Band Dispersion in an Organic Crystal
Authors: Koller G. , Berkebile S. , Oehzelt M. , Puschnig P. , Ambrosch-Draxl C. , Netzer F. P. , Ramsey M. G.
Published: July 2007

The high crystallinity of many inorganic materials allows their band structures to be determined through angle-resolved photoemission spectroscopy (ARPES). Similar studies of conjugated organic molecules of interest in optoelectronics are often hampered by difficulties in growing well-ordered and well-oriented crystals or films. We have grown crystalline films of uniaxially oriented sexiphenyl molecules and obtained ARPES data. Supported by density-functional calculations, we show that, in the direction parallel to the principal molecular axis, a quasi–one-dimensional band structure of a system of well-defined finite size develops out of individual molecular orbitals. In contrast, perpendicular to the molecules, the band structure reflects the periodicity of the molecular crystal, and continuous bands with a large dispersion were observed.
Fragile Frontiers in the Abyss
Authors: Van Dover Cindy Lee
Published: July 2007

The Silent Deep
. The Discovery, Ecology, and Conservation of the Deep Sea.
By Tony Koslow
. University of Chicago Press, Chicago, 2007. 292 pp. $35, £22.50. ISBN 9780226451251. University of New South Wales Press, Sydney, Australia. Aus $49.95. ISBN 9780868404158.

Koslow describes how and what we have learned of abyssal organisms and ecologies as well as the threats human activities pose to this ecosystem.
Immunoglobulins G, M, and A againstSporothrix schenckiiExoantigens in Patients with Sporotrichosis before and during Treatment with Itraconazole
Authors: Almeida-Paes Rodrigo , Pimenta Monique Amorim , Monteiro Paulo Cezar F. , Nosanchuk Joshua D. , Zancopé-Oliveira Rosely Maria
Published: July 2007

Sporotrichosis is an important subcutaneous mycosis, with an increasing worldwide incidence. However, few data are available regarding the immunological aspects ofSporothrix schenckiiinfection, particularly the humoral responses to the fungus. In this study we measured immunoglobulin G (IgG), IgM, and IgA in sera from 41 patients with sporotrichosis before antifungal treatment and from another 35 patients with sporotrichosis during itraconazole treatment by using a recently describedS. schenckiiexoantigen enzyme-linked immunosorbent assay (ELISA). More than 95% of patients had detectable IgA antibodies, and more than 85% had IgM and IgG antibodies before treatment. The number of patients with IgG antibodies increased to 91% during treatment. Conversely, significantly fewer samples from treated patients were positive for IgM (71%) and IgA (89%). Overall, 78% of patients had detectable levels of all isotypes tested at diagnosis, and this percentage dropped to 62.9% in patients receiving itraconazole. Testing of all three isotypes improved the sensitivity; at least two isotypes were detected in 93% of patients before and 89% after treatment. The reactivity of 94 sera from patients with other diseases and healthy individuals was also tested. Cross-reactivity occurred in 33% of the heterologous sera. Most of them were positive only in one isotype, 8.5% were positive for at least two isotypes, and only one serum (1.1%) was positive for the three isotypes. Antibodies produced duringS. schenckiiinfection are diverse, and we demonstrate that an exoantigen ELISA for the detection of combinations of IgA, IgG, and IgM antibodies is a highly sensitive and specific diagnostic assay for sporotrichosis.
Similarity of Bacterial Populations in Saliva from African-American Mother-Child Dyads
Authors: Li Yihong , Ismail Amid I. , Ge Yao , Tellez Marisol , Sohn Woosung
Published: July 2007

Using PCR-based denaturing gradient gel electrophoresis analyses of oral bacterial samples in 20 mother-child dyads, this study demonstrated a high degree of similarity of bacterial compositions between the mothers and their children; the two may share as much as 94% of their oral bacterial spectra, including cariogenic species.
Assessment of Use of Microsatellite Polymorphism Analysis for Improving Spatial Distribution Tracking of
Echinococcus multilocularis
Authors: Knapp J. , Bart J. M. , Glowatzki M. L. , Ito A. , Gerard S. , Maillard S. , Piarroux R. , Gottstein B.
Published: July 2007

Alveolar echinococcosis (AE)—caused by the cestode
Echinococcus multilocularis
—is a severe zoonotic disease found in temperate and arctic regions of the northern hemisphere. Even though the transmission patterns observed in different geographical areas are heterogeneous, the nuclear and mitochondrial targets usually used for the genotyping of
E. multilocularis
have shown only a marked genetic homogeneity in this species. We used microsatellite sequences, because of their high typing resolution, to explore the genetic diversity of
E. multilocularis
. Four microsatellite targets (EmsJ, EmsK, and EmsB, which were designed in our laboratory, and NAK1, selected from the literature) were tested on a panel of 76
E. multilocularis
samples (larval and adult stages) obtained from Alaska, Canada, Europe, and Asia. Genetic diversity for each target was assessed by size polymorphism analysis. With the EmsJ and EmsK targets, two alleles were found for each locus, yielding two and three genotypes, respectively, discriminating European isolates from the other groups. With NAK1, five alleles were found, yielding seven genotypes, including those specific to Tibetan and Alaskan isolates. The EmsB target, a tandem repeated multilocus microsatellite, found 17 alleles showing a complex pattern. Hierarchical clustering analyses were performed with the EmsB findings, and 29 genotypes were identified. Due to its higher genetic polymorphism, EmsB exhibited a higher discriminatory power than the other targets. The complex EmsB pattern was able to discriminate isolates on a regional and sectoral level, while avoiding overdistinction. EmsB will be used to assess the putative emergence of
E. multilocularis
in Europe.
Evaluation of Replication and Pathogenicity of Avian Influenza A H7 Subtype Viruses in a Mouse Model
Authors: Joseph Tomy , McAuliffe Josephine , Lu Bin , Jin Hong , Kemble George , Subbarao Kanta
Published: July 2007

Avian influenza A H7 subtype viruses pose a significant threat to human health because of their ability to transmit directly from domestic poultry to humans and to cause disease and, sometimes, death. Although it is important to develop vaccines against viruses of this subtype, very limited information is available on the immune response and pathogenesis of H7 viruses in animal models such as mice and ferrets. Ten H7 viruses were selected for possible vaccine development on the basis of their phylogenetic relationships and geographical locations. The virulence of the 10 viruses for mice and the immunogenicity of the viruses in mice and ferrets were evaluated to study the extent of antigenic relatedness and the level of cross-reactivity of antibodies. Most of the viruses showed similar patterns of cross-reactivity with mouse and ferret antisera. The Eurasian viruses elicited broadly cross-reactive antibodies that neutralized viruses from both Eurasian and North American lineages, but the converse was not true. A subset of the viruses was also evaluated for the ability to replicate and cause disease in BALB/c mice following intranasal administration. H7 subtype viruses were able to infect mice without adaptation and manifested different levels of lethality and kinetics of replication. On the basis of phylogenetic data, induction of broadly cross-neutralizing antibodies in mouse and ferret antisera, and their ability to replicate in mice, we have selected A/Netherlands/219/03 (subtype H7N7) and A/chicken/BC/CN-7/04 (subtype H7N3) viruses for vaccine development. The mouse model can be used for the preclinical evaluation of these vaccines against H7 subtype viruses.
A Functional Ubiquitin-Specific Protease Embedded in the Large Tegument Protein (ORF64) of Murine Gammaherpesvirus 68 Is Active during the Course of Infection
Authors: Gredmark Sara , Schlieker Christian , Quesada Victor , Spooner Eric , Ploegh Hidde L.
Published: July 2007

All herpesviruses contain a ubiquitin (Ub)-specific cysteine protease domain embedded within their large tegument protein, based on homology with the corresponding sequences of UL36 from herpes simplex virus type 1 and M48 from murine cytomegalovirus. This type of activity has yet to be demonstrated for cells infected with a gammaherpesvirus. By activity-based profiling, we show that the large tegument protein of murine gammaherpesvirus (MHV-68) ORF64 (273 kDa) is a functional deubiquitinating protease, as assessed by tandem mass spectrometry of adducts in extracts from MHV-68-infected cells that had been labeled with ubiquitin vinylmethylester, a ubiquitin-based active site-directed probe. The recombinantly expressed amino-terminal segment of ORF64 displays deubiquitinating activity toward Ub C-terminal 7-amido-4-methylcoumarin in vitro. The findings reported here for MHV-68 ORF64 extend those made for the alpha- and betaherpesvirus families and are consistent with an important, conserved enzymatic function of the tegument protein.
Mitochondrial role in ischemia–reperfusion of rat hearts exposed to high-K+cardioplegia and clonazepam: energetic and contractile consequences
Authors: Consolini A.E. , Ragone M.I. , Conforti P. , Volonté M.G.
Published: July 2007

The role of the mitochondrial Na/Ca-exchanger (mNCX) in hearts exposed to ischemia–reperfusion (I/R) and pretreated with cardioplegia (CPG) was studied from a mechano-calorimetric approach. No-flow ischemia (ISCH) and reperfusion (REP) were developed in isolated rat hearts pretreated with 10 µmol/L clonazepam (CLZP), an inhibitor of the mNCX, and (or) a high K+– low Ca2+solution (CPG). Left ventricular end diastolic pressure (LVEDP), pressure development during beats (P), and the steady heat release (Ht) were continuously measured and muscle contents of ATP and PCr were analyzed at the end of REP. During REP, Htincreased more than P, reducing muscle economy (P/Ht) and the ATP content. CPG induced an increase in P recovery during REP (to 90% ± 10% of preISCH) with respect to nonpretreated hearts (control, C, to 64% ± 10%, p < 0.05). In contrast, CLZP reduced P recovery of CPG-hearts (50% ± 6.4%, p < 0.05) and increased LVEDP in C hearts. To evaluate effects on sarcoplasmic reticulum (SR) function, ischemic hearts were reperfused with 10 mmol/L caffeine –36 mmol/L Na (C – caff – low Na). It increased LVEDP, which afterwards slowly relaxed, whereas Htincreased (by about 6.5 mW/g). CLZP sped up the relaxation with higher ΔHt, C – caff – low Na produced higher contracture and lower Htin perfused than in ischemic hearts. Values of ΔHtwere compared with reported fluxes of Ca2+-transporters, suggesting that mitochondria may be in part responsible for the ΔHtduring C – caff – low Na REP. Results suggest that ISCH–REP reduced the SR store for the recovery of contractility, but induced Ca2+movement from the mitochondria to the SR stores. Also, mitochondria and SR are able to remove cytosolic Ca2+during overloads (as under caffeine), through the mNCX and the uniporter. CPG increases Ca2+cycling from mitochondria to the SR, which contributes to the higher recovery of P. In contrast, CLZP produces a deleterious effect on ISCH–REP associated with higher heat release and reduced resynthesis of high energy phosphates, which suggests the induction of mitochondrial Ca cycling and uncoupling.
Investigation of the vasorelaxant effects of 3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole (YC-1) and diethylamine/nitric oxide (DEA/NO) on the human radial artery used as coronary bypass graft
Authors: Berkan Ocal , Bagcivan Ihsan , Kaya Tijen , Yildirim Kemal , Yildirim Sahin , Doğan Kasım
Published: July 2007

The radial artery (RA) is used as a spastic coronary bypass graft. This study was designed to investigate the mechanism of vasorelaxant effects of YC-1 (3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole), a nitric oxide (NO)-independent soluble guanylate cyclase (sGC) activator, and DEA/NO (diethylamine/nitric oxide), a NO-nucleophile adduct, on the human RA. RA segments (n = 25) were obtained from coronary artery bypass grafting patients and were divided into 3–4 mm vascular rings.Using the isolated tissue bath technique, the endothelium-independent vasodilatation function was tested in vitro by the addition of cumulative concentrations of YC-1 (10−10 to 3 × 10−7 mol/L) and DEA/NO (10−8 to 3 × 10−5 mol/L) following vasocontraction by phenylephrine in the presence or absence of 10−5 mol/L ODQ (1H-(1,2,4)oxadiazole(4,3-a)quinoxalin-1-one), the selective sGC inhibitor, 10−7 mol/L iberiotoxin, a blocker of Ca2+-activated K+ channels, or 10−5 mol/L ODQ plus 10−7 mol/L iberiotoxin. We also evaluated the effect of YC-1 and DEA/NO on the cGMP levels in vascular rings obtained from human radial artery (n = 6 for each drug). YC-1 (10−10 to 3 × 10−7 mol/L) and DEA/NO (10−8 to 3 × 10−5 mol/L) caused the concentration-dependent vasorelaxation in RA rings precontracted with phenylephrine (10−5 mol/L) (n = 20 for each drug). Pre-incubation of RA rings with ODQ, iberiotoxin, or ODQ plus iberiotoxin significantly inhibited the vasorelaxant effect of YC-1, but the inhibitor effect of ODQ plus iberiotoxin was significantly more than that of ODQ and iberiotoxin alone (p < 0.05). The vasorelaxant effect of DEA/NO almost completely abolished in the presence of ODQ and iberiotoxin plus ODQ, but did not significantly change in the presence of iberiotoxin alone (p > 0.05). The pEC50 value of DEA/NO was significantly lower than those for YC-1 (p < 0.01), with no change Emax values in RA rings. In addition, YC-1-stimulated RA rings showed more elevation in cGMP than that of DEA/NO (p < 0.05). These findings indicate that YC-1 is a more potent relaxant than DEA/NO in the human RA. The relaxant effects of YC-1 could be due to the stimulation of the sGC and Ca2+-sensitive K+channels, whereas the relaxant effects of DEA/NO could be completely due to the stimulation of the sGC. YC-1 and DEA/NO may be effective as vasodilator for the short-term treatment of perioperative spasm of coronary bypass grafts.
The effects of chronic trimetazidine treatment on mechanical function and fatty acid oxidation in diabetic rat hearts
Authors: Onay-Besikci Arzu , Guner Sahika , Arioglu Ebru , Ozakca Isil , Ozcelikay A. Tanju , Altan V. Melih
Published: July 2007

Clinical and experimental evidence suggest that increased rates of fatty acid oxidation in the myocardium result in impaired contractile function in both normal and diabetic hearts. Glucose utilization is decreased in type 1 diabetes, and fatty acid oxidation dominates for energy production at the expense of an increase in oxygen requirement. The objective of this study was to examine the effect of chronic treatment with trimetazidine (TMZ) on cardiac mechanical function and fatty acid oxidation in streptozocin (STZ)-diabetic rats. Spontaneously beating hearts from male Sprague–Dawley rats were subjected to a 60-minute aerobic perfusion period with a recirculating Krebs–Henseleit solution containing 11 mmol/L glucose, 100 μU/mL insulin, and 0.8 mmol/L palmitate prebound to 3% bovine serum albumin (BSA). Mechanical function of the hearts, as cardiac output × heart rate (in (mL/min)·(beats/min)·10–2), was deteriorated in diabetic (73 ± 4) and TMZ-treated diabetic (61 ± 7) groups compared with control (119 ± 3) and TMZ-treated controls (131 ± 6). TMZ treatment increased coronary flow in TMZ-treated control (23 ± 1 mL/min) hearts compared with untreated controls (18 ± 1 mL/min). The mRNA expression of 3-ketoacyl-CoA thiolase (3-KAT) was increased in diabetic hearts. The inhibitory effect of TMZ on fatty acid oxidation was not detected at 0.8 mmol/L palmitate in the perfusate. Addition of 1 μmol/L TMZ 30 min into the perfusion did not affect fatty acid oxidation rates, cardiac work, or coronary flow. Our results suggest that higher expression of 3-KAT in diabetic rats might require increased concentrations of TMZ for the inhibitory effect on fatty acid oxidation. A detailed kinetic analysis of 3-KAT using different concentrations of fatty acid will determine the fatty acid inhibitory concentration of TMZ in diabetic state where plasma fatty acid levels are increased.
Dexamethasone-induced insulin resistance is associated with increased connexin 36 mRNA and protein expression in pancreatic rat islets
Authors: Rafacho A. , Roma L.P. , Taboga S.R. , Boschero A.C. , Bosqueiro J.R.
Published: July 2007

Augmented glucose-stimulated insulin secretion (GSIS) is an adaptive mechanism exhibited by pancreatic islets from insulin-resistant animal models. Gap junction proteins have been proposed to contribute to islet function. As such, we investigated the expression of connexin 36 (Cx36), connexin 43 (Cx43), and the glucose transporter Glut2 at mRNA and protein levels in pancreatic islets of dexamethasone (DEX)-induced insulin-resistant rats. Study rats received daily injections of DEX (1 mg/kg body mass, i.p.) for 5 days, whereas control rats (CTL) received saline solution. DEX rats exhibited peripheral insulin resistance, as indicated by the significant postabsorptive insulin levels and by the constant rate for glucose disappearance (KITT). GSIS was significantly higher in DEX islets (1.8-fold in 16.7 mmol/L glucose vs. CTL, p < 0.05). A significant increase of 2.25-fold in islet area was observed in DEX vs. CTL islets (p < 0.05). Cx36 mRNA expression was significantly augmented, Cx43 diminished, and Glut2 mRNA was unaltered in islets of DEX vs. CTL (p < 0.05). Cx36 protein expression was 1.6-fold higher than that of CTL islets (p < 0.05). Glut2 protein expression was unaltered and Cx43 was not detected at the protein level. We conclude that DEX-induced insulin resistance is accompanied by increased GSIS and this may be associated with increase of Cx36 protein expression.
PARTICLE MESH HYDRODYNAMICS FOR ASTROPHYSICS SIMULATIONS
Authors: CHATELAIN PHILIPPE , COTTET GEORGES-HENRI , KOUMOUTSAKOS PETROS
Published: July 2007

We present a particle method for the simulation of three dimensional compressible hydrodynamics based on a hybrid Particle-Mesh discretization of the governing equations. The method is rooted on the regularization of particle locations as in remeshed Smoothed Particle Hydrodynamics (rSPH).

The rSPH method was recently introduced to remedy problems associated with the distortion of computational elements in SPH, by periodically re-initializing the particle positions and by using high order interpolation kernels.

In the PMH formulation, the particles solely handle the convective part of the compressible Euler equations. The particle quantities are then interpolated onto a mesh, where the pressure terms are computed. PMH, like SPH, is free of the convection CFL condition while at the same time it is more efficient as derivatives are computed on a mesh rather than particle-particle interactions. PMH does not detract from the adaptive character of SPH and allows for control of its accuracy. We present simulations of a benchmark astrophysics problem demonstrating the capabilities of this approach.
ELECTROKINETIC SLIP FLOW OF MICROFLUIDICS IN TERMS OF STREAMING POTENTIAL BY A LATTICE BOLTZMANN METHOD: A BOTTOM-UP APPROACH
Authors: FU XIN , LI BAOMING , ZHANG JUNFENG , TIAN FUZHI , KWOK DANIEL Y.
Published: July 2007

In traditional computational fluid dynamics, the effect of surface energetics on fluid flow is often ignored or translated into an arbitrary selected slip boundary condition in solving the Navier-Stokes equation. Using a bottom-up approach, we show in this paper that variation of surface energetics through intermolecular theory can be employed in a lattice Boltzmann method to investigate both slip and non-slip phenomena in microfluidics in conjunction with the description of electrokinetic phenomena for electrokinetic slip flow. Rather than using the conventional Navier-Stokes equation with a slip boundary condition, the description of electrokinetic slip flow in microfluidics is manifested by the more physical solid-liquid energy parameters, electrical double layer and contact angle in the mean-field description of the lattice Boltzmann method.
EXACT NONSPHERICAL RADIATING COLLAPSE
Authors: GHOSH S. G. , DESHKAR D. W.
Published: July 2007

We study the junction conditions for a nonspherical collapsing radiating star consisting of a shearing fluid undergoing radial heat flow with outgoing radiation. Radiation of the system is described by the plane symmetric version of the Vaidya solution. Junction conditions which match the collapse solutions to an exterior Vaidya metric show that, at the boundary, the pressure is proportional to the magnitude of the heat flow vector. Physical quantities, analogous to spherical symmetry related to the local conservation of momentum and surface redshift, are also obtained. Finally, exact gravitational collapse solutions, for both shear and shear-free cases, have been obtained by integrating a field equation.
LOCAL LAPLACIAN DETAIL LEARNING FOR FACE AGING MANIPULATION
Authors: SONG MINGLI , WANG HUIQIONG , CHEN CHUN
Published: July 2007

Face aging is a challenging work in image processing and computer animation field. In this paper, a novel local image Laplacian differential method is proposed to learn this complex face transformation. Firstly, together with the facial feature points correspondence, we extract the aging facial details from example face and apply to the target one by a global and a local Laplacian skin aging model respectively, and the latter makes the results more realistic in our experiment. Then, the skin color and hair style adjustments are carried out to simulate the aging process completely, making the results look more competitive and natural. Our experiment shows that our method is robust and appreciable.
A NEW BLIND ATTACK PROCEDURE FOR DCT-BASED IMAGE ENCRYPTION WITH SPECTRUM LEARNING
Authors: LI WEIHAI , YUAN YUAN
Published: July 2007

It is an important problem nowadays to ensure the security of encrypted multimedia contents on the Internet. In this paper, a new blind attack procedure called NZCA is proposed to decrypt images that are encrypted by DCT-based methods. It threatens almost all existing DCT-based image encryption methods without the need of knowing the encryption algorithm details. The parameters of the NZCA can be adaptively selected via unsupervised learning with spectrum analysis of image projection. The effectiveness of the NZCA has been quantitatively evaluated by comparing the decrypted images with the edge sketches of original images. Our experiments on a number of real-world images show that NZCA is very powerful. Furthermore, we point out that a special form of inter-block shuffle, full inter-block shuffle (FIBS), is immune to the NZCA. Hence we suggest that all DCT-based image encryption methods for JPEG, MPEG, H.26x, etc. employ the FIBS so as to enhance the security.
Ouabain stimulates protein kinase B (Akt) phosphorylation in opossum kidney proximal tubule cells through an ERK-dependent pathway
Authors: Khundmiri Syed J. , Amin Vishal , Henson Jeff , Lewis John , Ameen Mohamed , Rane Madhavi J. , Delamere Nicholas A.
Published: July 2007

Endogenous cardiotonic glycosides bind to the inhibitory binding site of the plasma membrane sodium pump (Na+/K+-ATPase). Plasma levels of endogenous cardiotonic glycosides increase in several disease states, such as essential hypertension and uremia. Low concentrations of ouabain, which do not inhibit Na+/K+-ATPase, induce cell proliferation. The mechanisms of ouabain-mediated response remain unclear. Recently, we demonstrated that in opossum kidney (OK) proximal tubular cells, low concentrations of ouabain induce cell proliferation through phosphorylation of protein kinase B (Akt) in a calcium-dependent manner. In the present study, we identified ERK as an upstream kinase regulating Akt activation in ouabain-stimulated cells. Furthermore, we provide evidence that low concentrations of ouabain stimulate Na+/K+-ATPase-mediated 86Rb uptake in an Akt-, ERK-, and Src kinase-dependent manner. Ouabain-mediated ERK phosphorylation was inhibited by blockade of intracellular calcium release, calcium entry, tyrosine kinases, and phospholipase C. Pharmacological inhibition of phosphoinositide-3 kinase and Akt failed to inhibit ouabain-stimulated ERK phosphorylation. Ouabain-mediated Akt phosphorylation was inhibited by U0126, a MEK/ERK inhibitor, suggesting that ouabain-mediated Akt phosphorylation is dependent on ERK. In an in vitro kinase assay, active recombinant ERK phosphorylated recombinant Akt on Ser473. Moreover, transient transfection with constitutively active MEK1, an upstream regulator of ERK, increased Akt phosphorylation and activation, whereas overexpression of constitutively active Akt failed to stimulate ERK phosphorylation. Ouabain at low concentrations also promoted cell proliferation in an ERK-dependent manner. These findings suggest that ouabain-stimulated ERK phosphorylation is required for Akt phosphorylation on Ser473, cell proliferation, and stimulation of Na+/K+-ATPase-mediated 86Rb uptake in OK cells.
Hydrogen sulfide downregulates the aortic l-arginine/nitric oxide pathway in rats
Authors: Geng Bin , Cui Yuying , Zhao Jing , Yu Fang , Zhu Yi , Xu Geyang , Zhang Zhiwen , Tang Chaoshu , Du Junbao
Published: July 2007

The aim of the present study was to investigate the effect of hydrogen sulfide (H2S) signaling by nitric oxide (NO) in isolated rat aortas and cultured human umbilical vein endothelial cells (HUVECs). Both administration of H2S and NaHS, as well as endogenous H2S, reduced NO formation, endothelial nitric oxide synthase (eNOS) activity, eNOS transcript abundance, and l-arginine (l-Arg) transport (all P < 0.01). The kinetics analysis of eNOS activity and l-Arg transport showed that H2S reduced Vmax values (all P < 0.01) without modifying Km parameters. Use of selective NOS inhibitors verified that eNOS [vs. inducible NOS (iNOS) and neuronal NOS (nNOS)] was the specific target of H2S regulation. H2S treatment (100 μmol/l) reduced Akt phosphorylation and decreased eNOS phosphorylation at Ser1177. H2S reduced l-Arg uptake by inhibition of a system y+ transporter and decreased the CAT-1 transcript. H2S treatment reduced protein expression of eNOS but not of nNOS and iNOS. Pinacidil (KATP channel opener) exhibited the similar inhibitory effects on the l-Arg/NOS/NO pathway. Glibenclamide (KATP channel inhibitor) partly blocked the inhibitory effect of H2S and pinacidil. An in vivo experiment revealed that H2S downregulated the vascular l-Arg/eNOS/NO pathway after intraperitoneal injection of NaHS (14 μmol/kg) in rats. Taken together, our findings suggest that H2S downregulates the vascular l-Arg/NOS/NO pathway in vitro and in vivo, and the KATP channel could be involved in the regulatory mechanism of H2S.
Interaction of apolipoprotein AIV with cholecystokinin on the control of food intake
Authors: Lo Chun Min , Zhang Dian Ming , Pearson Kevin , Ma Liyun , Sun William , Sakai Randall R. , Davidson W. Sean , Liu Min , Raybould Helen E. , Woods Stephen C. , Tso Patrick
Published: July 2007

Apolipoprotein AIV (apo AIV) and cholecystokinin (CCK) are peptides that act both peripherally and centrally to reduce food intake by decreasing meal size. The present study examined the effects of intraperitoneally administered bolus doses of recombinant apo AIV, CCK-8, and a combination of subthreshold doses of apo AIV and CCK on 4-h food intake in rats that were fasted overnight. Apo AIV at 100 μg/kg reduced food intake significantly relative to the saline control for 1 h, as did doses of CCK-8 at or above 0.125 μg/kg. Doses of apo AIV (50 μg/kg) or CCK (0.06 μg/kg) alone had no effect on food intake. However, when these subthreshold doses of apo AIV and CCK were administered together, the combination produced a significant inhibition of food intake relative to saline controls ( P < 0.001), and the duration of the effect was longer than that caused by the administration of either apo AIV or CCK alone. The satiation effect produced by CCK-8 + apo AIV was attenuated by lorglumide, a CCK1 receptor antagonist. We conclude that, whereas the intraperitoneal administration of doses of either recombinant apo AIV or CCK at or above threshold levels reduces food intake, the coadministration of subthreshold doses of the two peptides is highly satiating and works via CCK1 receptor.
Probiotics potentiate IL-6 production in IL-1β-treated Caco-2 cells through a heat shock-dependent mechanism
Authors: Reilly Natasha , Poylin Vitaliy , Menconi Michael , Onderdonk Andrew , Bengmark Stig , Hasselgren Per-Olof
Published: July 2007

IL-6 may exert anti-inflammatory and protective effects in intestinal mucosa and enterocytes. The influence of probiotics on mucosal and enterocyte IL-6 production is not known. We tested the hypothesis that the probiotic bacteria Lactobacillus paracasei and Lactobacillus plantarum regulate IL-6 production in intestinal epithelial cells. Cultured Caco-2 cells were treated with 1 ng/ml of IL-1β in the absence or presence of different concentrations of L. paracasei or L. plantarum followed by measurement of IL-6 production. The role of heat shock response was examined by determining the expression of heat shock protein 70 (hsp70) and hsp27, by downregulating their expression with small interfering RNA (siRNA), or by treating cells with quercetin. Treatment of the Caco-2 cells with IL-1β resulted in increased IL-6 production, confirming previous reports from this laboratory. Probiotics alone did not influence IL-6 production, but the addition of probitoics to IL-1β-treated cells resulted in a substantial augmentation of IL-6 production. Treatment of the Caco-2 cells with live L. paracasei increased cellular levels of hsp70 and hsp27 and the potentiating effect on IL-6 production was inhibited by quercetin and by hsp70 or hsp27 siRNA. Results suggest that probiotics may enhance IL-6 production in enterocytes subjected to an inflammatory stimulus and that this effect may, at least in part, be heat shock dependent.
The HIF-1 response to simulated ischemia in mouse skeletal muscle cells neither enhances glycolysis nor prevents myotube cell death
Authors: Dehne Nathalie , Kerkweg Uta , Otto Teresa , Fandrey Joachim
Published: July 2007

Hypoxia-inducible factor (HIF) plays an important role in regulating gene expression in response to ischemia. Although activation of HIF-1 in muscle tissue was found during ischemia in vivo, the meaning and mechanisms in isolated cells are still incompletely understood. We studied activation of HIF-1 in skeletal muscle cells cultured in either their undifferentiated myoblast state or differentiated into myotubes. HIF-1 was activated in myoblasts and myotubes by hypoxia and simulated ischemia. Induction of adrenomedullin mRNA and, to a lesser extent, VEGF mRNA correlated well with the induction of HIF-1α protein in both cell types. Enzymes of glycolysis-like lactate dehydrogenase and pyruvate kinase showed upregulation of their mRNA only under hypoxic conditions but not during simulated ischemia. Phosphofructokinase mRNA showed no significant upregulation at all. Although HIF-1 was activated in myotubes during simulated ischemia, myotubes died preceded by a loss of ATP. Myoblasts survived simulated ischemia with no decrease in ATP or ATP turnover. Furthermore, pharmacological inhibition of HIF-1 hydroxylases by dimethyloxalylglycine (DMOG) increased HIF-1α accumulation and significantly upregulated the expression of adrenomedullin, VEGF, lactate dehydrogenase, and pyruvate kinase in myoblasts and myotubes. However, DMOG provided no protection from cell death. Our data indicate that HIF-1, although activated in myotubes during simulated ischemia, cannot protect against the loss of ATP and cell viability. In contrast, myoblasts survive ischemia and thus may play an important role during regeneration and HIF-1-induced revascularization.