bluuebunny/crossref_metadata_2025 huggingface dataset:
Tardive dyskinesia and glucid metabolism
Authors: Brousse Georges , Meary Alexandre , Mouret Jacques , Blanc Olivier , Hueber Thierry , Lemoine Philippe , Llorca Pierre‐Michel , Lachaux Bernard
Published: June 2007

A role of insulin‐dependent diabetes in the onset of tardive dyskinesia has been reported and relies on weak physiopathological evidence.

Objective

To study the relationship between the occurrence of tardive dyskinesia and variations in glucose levels in a population of patients under typical antipsychotic treatment.

Methods

Sixty‐nine patients with a schizophrenic disorder and who had been receiving continuous neuroleptic treatment for at least 2 years were included. Tardive dyskinesias were assessed by the Abnormal Involuntary Movements Scale (AIMS) and glucose levels by glucose oxidase method.

Results

No significant differences in values of fasting glucose (FG) levels, post‐prandial glucose (PPG) levels and glycosylated haemoglobin between the groups with and without tardive dyskinesia were found. In the sub‐group with normal FG, comparison of post‐prandial delta glucose levels (difference between PPG and FG) between the two group with and without tardive dyskinesia showed a significant difference (p < 0.05). This comparison also showed a correlation between post‐prandial delta glucose levels and the AIMS score in the group with tardive dyskinesia (r = 0.482, p < 0.05).

Conclusion

Glucose metabolism could be involved in patients with tardive dyskinesia. Various factors outside antipsychotic treatment can favour a disturbance of glucose metabolism, which may not be severe. Copyright © 2007 John Wiley & Sons, Ltd.
Cytotoxic action of phorbol esters on human pancreatic cancer cells
Authors: Bond Jane A. , Gescher Andreas J. , Verschoyle Richard D. , Lemoine Nicholas R. , Errington Rachel , Wiltshire Marie , Smith Paul J. , Wynford‐Thomas David
Published: June 2007

We previously showed that phorbol esters are cytotoxic to human thyroid epithelial cells expressing a mutant RAS oncogene. Here we explore the generality of this finding using cells derived from pancreatic cancer, which, like thyroid, shows a high frequency of RAS mutation, but is a much greater cause of cancer mortality. The response to phorbol myristate acetate (PMA) and related agents was assessed on a panel of 9 pancreatic cancer cell lines, using a range of assays for cell growth and death in vitro and in vivo. In most lines, PMA induced non‐apoptotic cell death which was, surprisingly, independent of its “classic” target, protein kinase C. With 24 hr exposure, the IC50 in the most sensitive line (Aspc‐1) was <1 ng/ml (1.6 nM), with survival undetectable at concentrations ≥≥16 nM, and after only 1 hr exposure the IC50 was still ≤≤16 nM. Interestingly, the efficacy of a second phorbol ester, phorbol dibutyrate, was much lower, and the PMA analogue bryostatin‐1, which is in clinical trials against other tumour types, was totally inactive. Pre‐treatment of Aspc‐1 cells with PMA before subcutaneous inoculation into nude mice prevented, or greatly retarded, subsequent xenograft tumour growth. Furthermore, treatment of established tumours with a single peri‐tumoral injection of PMA induced extensive cell death and arrested tumour development. Taken together with recent Phase 1 clinical studies, these data suggest that activity against pancreatic cancer will be attainable by systemic administration of PMA, and point to potential novel therapeutic targets for this highly aggressive cancer. © 2007 Wiley‐Liss, Inc.
DNA global hypomethylation in squamous cell head and neck cancer associated with smoking, alcohol consumption and stage
Authors: Smith Ian M. , Mydlarz Wojciech K. , Mithani Suhail K. , Califano Joseph A.
Published: June 2007

Epigenetic changes have been implicated in the pathogenesis of solid tumors, including head and neck squamous cell carcinoma (HNSCC). Prior efforts have primarily examined regional promoter hypermethylation as a silencer of tumor suppressor gene expression. To analyze the global state of methylation in the HNSCC genome, we utilize pyrosequencing of repetitive elements (LINEs) to compare the state of global methylation in HNSCC to normal aerodigestive mucosa. 137 samples (119 HNSCC tumors and 18 normal mucosal tissues) were digested to extract DNA and subjected to bisulfite treatment. Treated DNA was amplified using PCR primers for the repetitive LINEs sequence and produced a heterogeneous sample of products, from many genomic loci. These products were pyrosequenced to quantitatively evaluate their global genomic methylation status. HNSCC specimens showed global hypomethylation, with a mean level of genomic methylation of 46.8% methylated with a standard deviation of 9.0. Conversely, the normal upper airway mucosa had a global methylation level of 54.0 and a standard deviation of 4.6 (Mann–Whitney p value < 0.001). The tumor specimens also showed an increasing degree of hypomethylation associated with advanced tumor stage (ANOVA p‐value of 0.003). About 67% of HNSCC's are globally hypomethylated when evaluated against the minimum level of methylation in the normal mucosal specimens. Degree of global hypomethylation was associated with smoking history, alcohol use and stage in univariate analysis (p‐value 0.02), however, only HNSCC diagnosis remained significant on multivariate analysis. Despite the presence of regional promoter hypermethylation, HNSCC demonstrates global genomic hypomethylation. The effects of stage, alcohol use and smoking on global hypomethylation were not independently significant. © 2007 Wiley‐Liss, Inc.
CD4+CD25hi regulatory T‐cell frequency correlates with persistence of human papillomavirus type 16 and T helper cell responses in patients with cervical intraepithelial neoplasia
Authors: Molling Johan W. , de Gruijl Tanja D. , Glim Judith , Moreno Maria , Rozendaal Lawrence , Meijer Chris J.L.M. , van den Eertwegh Alfons J.M. , Scheper Rik J. , von Blomberg Mary E. , Bontkes Hetty J.
Published: June 2007

CD4+CD25hiCTLA4+FoxP3+ regulatory T cells (Treg) have been shown to maintain immune tolerance against self antigens and increased circulating frequencies have been reported in various types of cancers. Circulating invariant natural killer T‐cells (iNKT) are reduced in cancer patients and low iNKT frequency is related to poor prognosis. It is not yet clear whether high Treg numbers and low iNKT cell numbers pose an increased risk for the progression of premalignant lesions or whether Treg and iNKT cell numbers are influenced by dysplasia. We therefore studied prospectively the relation between iNKT cell and Treg frequencies and the natural course of human papillomavirus type 16 (HPV16) induced pre‐malignant cervical dysplasia in 82 patients who participated in a nonintervention cohort study of women with abnormal cytology. Treg frequencies were significantly increased in women who had persistent HPV16 infection. Within the HPV16 persistence group there was no difference in Treg frequencies among patients who developed a CIN3 lesion and patients who did not progress to CIN3. Furthermore, Treg frequencies were increased in patients who had detectable HPV16 E7 specific IL‐2 producing T‐helper cells, which suggests a causal role of HPV infection in Treg development in parallel with HPV16 specific T helper cells. No evidence was found for a role for iNKT cells in persistence of HPV16 and progression of HPV16 induced CIN lesions. However, HPV‐persistence‐associated Tregs may explain the inefficacy of concomitant persistence associated immunity and may contribute to subsequent progression to neoplasia. © 2007 Wiley‐Liss, Inc.
Relationship between ornithine decarboxylase levels in anaplastic gliomas and progression‐free survival in patients treated with DFMO–PCV chemotherapy
Authors: Levin Victor A. , Jochec Jacob L. , Shantz Lisa M. , Aldape Kenneth D.
Published: June 2007

The purpose of this study was to assess the relationship between progression‐free survival (PFS) in patients treated with DFMO + PCV (procarbazine, CCNU, vincristine) chemotherapy for malignant gliomas with tumor cell ornithine decarboxylase (ODC) activity. Formalin‐fixed slides were obtained for study patients with anaplastic gliomas (AGs) and glioblastoma treated on protocol DM92‐035. ODC levels were measured using an antibody to ODC coupled to Alexa 647 dye (Ab‐ODC‐Alexa 647). Ab‐ODC‐Alexa 647 intensity in transgenic murine hearts of differing ODC activity was used to calculate ODC activity in tumor cell nucleoplasm. In total, tumor specimens for 31 of 114 (27%) patients treated on the AG strata and 10 patients from the GBM strata were obtained. We found that tumor ODC level heterogeneity increased with increasing tumor malignancy. In a Cox proportional hazards model, PFS was found to be inversely related to median tumor ODC activity, with an unadjusted hazard ratio for median ODC group (>3.3 vs. ≤3.3 nmol/30 min/μg protein) of 5.8 (p < 0.0001); a median PFS of 522 weeks for patients with AGs with median ODC activity ≤ 3.3 and 31 weeks for the 8 AG and 10 glioblastoma patients with ODC activity > 3.3 nmol/30 min/μg protein. Of AG tumors in which ODC activity was evaluated, 26% had ODC levels > 3.3 nmol/30 min/μg protein. This study shows that Ab‐ODC‐Alexa 647 fluorescence intensity can be used as a surrogate marker of ODC biochemical activity in AGs and can predict PFS to DFMO‐based chemotherapy. © 2007 Wiley‐Liss, Inc.
Lymphocyte radiosensitivity in BRCA1 and BRCA2 mutation carriers and implications for breast cancer susceptibility
Authors: Barwell Julian , Pangon Laurent , Georgiou Anne , Kesterton Ian , Langman Caroline , Arden‐Jones Audrey , Bancroft Elizabeth , Salmon Ashi , Locke Imogen , Kote‐Jarai Zsofia , Morris Joanna R. , Solomon Ellen , Berg Jonathan , Docherty Zoe , Camplejohn Richard , Eeles Rosalind , Hodgson Shirley V.
Published: June 2007

There is conflicting evidence as to whether individuals who are heterozygous for germ‐line BRCA1 or BRCA2 mutations have an altered phenotypic cellular response to irradiation. To investigate this, chromosome breakage and apoptotic response were measured after irradiation in peripheral blood lymphocytes from 26 BRCA1 and 18 BRCA2 mutation carriers without diagnosed breast cancer, and 38 unaffected age, ethnically and sex‐matched controls. To assess the role of BRCA1 and BRCA2 in homologous recombination, an S phase enrichment chromosome breakage assay was used. BrdUrd incorporation studies allowed verification of the correct experimental settings. We found that BRCA1 mutation carriers without cancer had increased chromosome breaks as well as breaks and gaps per cell post irradiation using the classical G2 assay (p = 0.01 and 0.004, respectively) and the S phase enrichment assay (p = 0.01 and 0.01, respectively) compared to age‐matched unaffected controls. BRCA2 mutation carriers without cancer had increased breaks as well as breaks and gaps per cell post irradiation using the S phase enrichment assay (p = 0.045 and 0.012, respectively). No difference was detected using the G2 assay (p = 0.88 and 0.40 respectively). BRCA1 and BRCA2 mutation carriers had normal cell cycle kinetics and apoptotic response to irradiation compared to age‐matched controls. Our results show a demonstrable impairment in irradiation induced DNA repair in women with heterozygous germline BRCA1 and BRCA2 mutations prior to being diagnosed with breast cancer. © 2007 Wiley‐Liss, Inc.
ATM sequence variants associate with susceptibility to non‐small cell lung cancer
Authors: Yang Hushan , Spitz Margaret R. , Stewart David J. , Lu Charles , Gorlov Ivan P. , Wu Xifeng
Published: June 2007

ATM gene mutations have been implicated in many human cancers. However, the role of ATM polymorphisms in lung carcinogenesis is largely unexplored. We conducted a case‐control analysis of 556 Caucasian non‐small‐cell lung cancer (NSCLC) patients and 556 controls frequency‐matched on age, gender and smoking status. We genotyped 11 single nucleotide polymorphisms of the ATM gene and found that compared with the wild‐type allele‐containing genotypes, the homozygous variant genotypes of ATM08 (rs227060) and ATM10 (rs170548) were associated with elevated NSCLC risk with ORs of 1.55 (95% CI: 1.02–2.35) and 1.51 (0.99–2.31), respectively. ATM haplotypes and diplotypes were inferred using the Expectation‐Maximization algorithm. Haplotype H5 was significantly associated with reduced NSCLC risk in former smokers with an OR of 0.47 (0.25–0.96) compared with the common H1 haplotype. Compared with the H1–H2 diplotype, H2–H2 and H3–H4 diplotypes were associated with increased NSCLC risk with ORs of 1.58 (0.99–2.54) and 2.29 (1.05–5.00), respectively. We then evaluated genotype–phenotype correlation in the control group using the comet assay to determine DNA damage and DNA repair capacity. Compared with individuals with at least 1 wild‐type allele, the homozygous variant carriers of either ATM08 or ATM10 exhibited significantly increased DNA damage as evidenced by a higher mean value of the radiation‐induced olive tail moment (ATM08: 4.86 ± 2.43 vs. 3.79 ± 1.51, p = 0.04; ATM10: 5.14 ± 2.37 vs. 3.79 ± 1.54, p = 0.01). Our study presents the first epidemiologic evidence that ATM genetic variants may affect NSCLC predisposition, and that the risk‐conferring variants might act through down‐regulating the functions of ATM in DNA repair activity upon genetic insults such as ionizing radiation. © 2007 Wiley‐Liss, Inc.
Zinc toxicity alters mitochondrial metabolism and leads to decreased ATP production in hepatocytes
Authors: Lemire Joseph , Mailloux Ryan , Appanna Vasu D.
Published: June 2007

Although zinc (Zn) is a known environmental toxicant, its impact on the cellular energy‐producing machinery is not well established. This study investigated the influence of this divalent metal on the oxidative ATP producing network in human hepatocellular carcinoma (HepG2) cells. Zn‐challenged cells contained more oxidized proteins and lipids compared with control cells. Zn severely impeded mitochondrial functions by inhibiting aconitase, α‐ketoglutarate dehydrogenase, isocitrate dehydrogenase‐NAD+ dependent, succinate dehydrogenase and cytochrome C oxidase Zn‐exposed cells had a disparate mitochondrial metabolism compared with the control cells and produced significantly less ATP. However, the expression of isocitrate dehydrogenase‐NADP+ dependent was more prominent in cells treated with Zn. Hence, Zn‐induced pathologies may be due to the inability of the mitochondria to generate energy effectively. Copyright © 2007 John Wiley & Sons, Ltd.
The antioxidant and pro‐oxidant activity of vitamin C and trolox in vitro: a comparative study
Authors: Poljšak Borut , Raspor Peter
Published: June 2007

The antioxidant and pro‐oxidant properties of ascorbic acid (vitamin C) and the water‐soluble analogue of α‐tocopherol (trolox) were compared. Trolox has advantages over α‐tocopherol, the latter being only lipid‐soluble due to the presence of a carboxyl group in lieu of a phytol chain which imparts trolox with water solubility. Trolox is used as a standard antioxidant in biochemical studies against which the antioxidant capacity of compounds is compared. Although ascorbic acid and tocopherols possess strong antioxidant properties, they might also exhibit pro‐oxidant properties in the presence of free transition metals. Thus, reactions detailed in this study were performed in the presence of Cr(VI) in an effort to investigate the potential of ascorbic acid and trolox to generate hydroxyl radicals in a Fenton‐like reaction. Results obtained were derived from reactions containing the same concentration of ascorbic acid and trolox under identical experimental conditions. Hydroxyl radical formation was observed in the reaction of Cr(VI) with ascorbic acid resulting from ascorbic acid auto‐oxidation and H2O2 formation. Hydroxyl radical formation was only detected in the reaction mixture containing Cr(VI) and trolox following the addition of H2O2. Copyright © 2007 John Wiley & Sons, Ltd.
Captan: Transition from ‘B2’ to ‘not likely’. How pesticide registrants affected the EPA Cancer Classification Update
Authors: Gordon Elliot
Published: June 2007

On 24 November 2004 EPA changed the cancer classification of captan from a ‘probable human carcinogen’ (Category B2) to ‘not likely’ when used according to label directions. The new cancer classification considers captan to be a potential carcinogen at prolonged high doses that cause cytotoxicity and regenerative cell hyperplasia. These high doses of captan are many orders of magnitude above those likely to be consumed in the diet, or encountered by individuals in occupational or residential settings. This revised cancer classification reflects EPA's implementation of their new cancer guidelines.

The procedures involved in the reclassification effort were agreed upon with EPA and involved an Independent Transparent Review as it related to four components that formed the basis of the original 1986 B2 classification: mouse tumors; rat tumors; mutagenicity; and structural similarity to other carcinogens.

A Peer Review Panel organized and administered by Toxicology Excellence for Risk Assessment (TERA) met on 2–3 September 2003. The Panel concluded that captan acted through a non‐mutagenic threshold mode of action that required prolonged irritation of the duodenal villi as the initial key event.

EPA's Cancer Assessment Review Committee (CARC) met on 9 June 2004 and endorsed the Peer Review findings. EPA intended to have the FIFRA Scientific Advisory Panel (SAP) consider the basis for this reclassification but found the science was robust and judged that a SAP review was not warranted.

Using the revised classification, the margin of exposure is approximately 1,200,000, supporting the ‘not likely’ characterization. Copyright © 2007 John Wiley & Sons, Ltd.
Urinary excretion of toluene diisocyanates in rats following dermal exposure
Authors: Yeh Hui‐Jung , Lin Wei‐Chao , Shih Tung‐Sheng , Tsai Perng‐Jy , Wang Shan‐Tair , Chang Ho‐Yuan
Published: June 2007

Toluene diisocyanates (TDI) are commonly used in polyurethane (PU)‐related products. TDIs have been documented as the leading cause of occupational asthma. Skin exposure to TDI in the workplace is common. However, no studies in the literature have investigated the exact biomarker concentration profile for skin TDI absorption through any in vivo animal studies. In this study a rat model was used to evaluate the TDI skin absorption to explore the dose‐response pattern and to determine the kinetic characteristics of urinary toluene diamine (U‐TDA) during skin exposure. TDIs were topically exposed on the dorsum of rat skin at 0.2%, 1% and 5%. Consecutive urine samples were collected for 6 days and U‐TDA were analysed using GC/ECD. It was demonstrated in this rat study that absorption of 2,4‐ and 2,6‐TDI through skin contact is possible. A clear dose‐dependent skin absorption relationship for 2,4‐ and 2,6‐TDI was demonstrated by the AUC, Cmax findings and accumulative amounts (r ≥ 0.968). U‐TDA concentration profiles in 6‐day consecutive urine samples fit well in the first‐order kinetics, although higher order kinetics could not be excluded for the high dose. The apparent half‐lives for excretory urinary TDA were about 20 h consistent at various skin exposures. It is concluded that skin absorption of TDI was confirmed in a rat model and a clear dose‐dependent skin absorption relationship for 2,4‐ and 2,6‐TDI was demonstrated. Excretory U‐TDA concentrations in 6‐day consecutive urine samples via skin exposure reveal the first‐order kinetics and the half‐lives were about 20 h. Copyright © 2007 John Wiley & Sons, Ltd.
Preliminary investigation of changes in the sexually dimorphic nucleus of the rat medial preoptic area following prenatal exposure to fenitrothion
Authors: Struve Melanie F. , Turner Katie J. , Dorman David C.
Published: June 2007

In vitro, the organophosphate insecticide fenitrothion is a potent competitive androgen receptor antagonist, whereas in vivo it affects the development of the male rat reproductive system. The purpose of this pilot study was to determine whether prenatal exposure to fenitrothion affects development of the rat sexually dimorphic nucleus of the medial preoptic area (SDN‐POA). Pregnant rats (n = 5–6 litters/group) were orally dosed with corn oil (vehicle) or fenitrothion (20 or 25 mg kg−1 day−1) from gestation day (GD) 12–21. Offspring were euthanized after reaching sexual maturity (females 60–65 days old and males 96–105 days old) and the SDN‐POA volumes determined for two rats/sex/litter. Tremors, increased lacrimation and decreased body weight gain were observed in dams from both fenitrothion exposure groups. Reproductive effects in male offspring, including reduced anogenital distance on postnatal day (PND) 1 and increased retention of areolae (PND 13) were observed following fenitrothion exposure at these dose levels. These effects did not persist into adulthood. There was a dose‐related increase in the SDN‐POA volume in males and a dose‐related decrease in SDN‐POA volume in females exposed to fenitrothion. These SDN‐POA volume changes contrast with those seen with flutamide, another potent anti‐androgen, and suggest that fenitrothion may have mixed endocrine effects on the developing brain. Copyright © 2007 John Wiley & Sons, Ltd.
Thimerosal distribution and metabolism in neonatal mice: comparison with methyl mercury
Authors: Zareba Grazyna , Cernichiari Elsa , Hojo Rieko , Nitt Scott Mc , Weiss Bernard , Mumtaz Moiz M. , Jones Dennis E. , Clarkson Thomas W.
Published: June 2007

Thimerosal, which releases the ethyl mercury radical as the active species, has been used as a preservative in many currently marketed vaccines throughout the world. Because of concerns that its toxicity could be similar to that of methyl mercury, it is no longer incorporated in many vaccines in the United States. There are reasons to believe, however, that the disposition and toxicity of ethyl mercury compounds, including thimerosal, may differ substantially from those of the methyl form. The current study sought to compare, in neonatal mice, the tissue concentrations, disposition and metabolism of thimerosal with that of methyl mercury. ICR mice were given single intramuscular injections of thimerosal or methyl mercury (1.4 mg Hg kg−1) on postnatal day 10 (PND 10). Tissue samples were collected daily on PND 11–14. Most analysed tissues demonstrated different patterns of tissue distribution and a different rate of mercury decomposition. The mean organic mercury in the brain and kidneys was significantly lower in mice treated with thimerosal than in the methyl mercury‐treated group. In the brain, thimerosal‐exposed mice showed a steady decrease of organic mercury levels following the initial peak, whereas in the methyl mercury‐exposed mice, concentrations peaked on day 2 after exposure. In the kidneys, thimerosal‐exposed mice retained significantly higher inorganic mercury levels than methyl mercury‐treated mice. In the liver both organic and inorganic mercury concentrations were significantly higher in thimerosal‐exposed mice than in the methyl mercury group. Ethyl mercury was incorporated into growing hair in a similar manner to methyl mercury. The data showing significant kinetic differences in tissue distribution and metabolism of mercury species challenge the assumption that ethyl mercury is toxicologically identical to methyl mercury. Copyright © 2007 John Wiley & Sons, Ltd.
Protection of multiple antioxidants Chinese herbal medicine on the oxidative stress induced by adriamycin chemotherapy
Authors: Qin Xu‐Jun , He Wei , Hai Chun‐Xu , Liang Xin , Liu Rui
Published: June 2007

Adriamycin is an effective anthracycline anti‐tumor antibiotic. However, the clinical use of adriamycin has been restricted by its serious side effects. Some reports indicated that the side effects of adriamycin could cause systemic injury, in which reactive oxygen species (ROS) play an important role. ROS are a large family of oxygen free radical and non‐free radical active oxygen‐containing molecules, including superoxide radical, hydrogen peroxide and hydroxyl radical, which contribute to oxidative stress. Although antioxidant treatment is a promising method to prevent the side effects, protection by a single antioxidant is limited. The Chinese herbal medicine ANTIOXIN is a multiple antioxidant that can effectively block oxidative stress. It was hypothesized that ANTIOXIN could effectively reduce the side effects of adriamycin. A rat tumor model with a transplanted tumor in the liver was treated with adriamycin and ANTIOXIN was used as a protection. Oxidative stress and antioxidant enzymes were evaluated. The results showed that adriamycin chemotherapy increased the level of malondialdehyde (MDA), nitrogen oxide (NO) and decreased the activities of total superoxide dismutase (T‐SOD), manganese superoxide dismutase (MnSOD), catalase (CAT), glutathione (GSH) and total antioxidant capacity (TAC). Adriamycin chemotherapy also decreased the expression of Bcl‐2, increased the expression of iNOS and cell apoptosis in the liver and kidney. Multiple antioxidants ANTIOXIN had an antagonistic effect on these changes and significantly decreased the mortality of the experimental rats. These data demonstrated that adriamycin chemotherapy could cause oxidative stress to the whole body, on which multiple antioxidants based on the theory of ‘multiple antioxidant chain’ had effective protection. Copyright © 2007 John Wiley & Sons, Ltd.
On the independence number of the Erdős‐Rényi and projective norm graphs and a related hypergraph
Authors: Mubayi Dhruv , Williford Jason
Published: June 2007

The Erdős‐Rényi and Projective Norm graphs are algebraically defined graphs that have proved useful in supplying constructions in extremal graph theory and Ramsey theory. Their eigenvalues have been computed and this yields an upper bound on their independence number. Here we show that in many cases, this upper bound is sharp in the order of magnitude. Our result for the Erdős‐Rényi graph has the following reformulation: the maximum size of a family of mutually non‐orthogonal lines in a vector space of dimension three over the finite field of order q is of order q3/2. We also prove that every subset of vertices of size greater than q2/2 + q3/2 + O(q) in the Erdős‐Rényi graph contains a triangle. This shows that an old construction of Parsons is asymptotically sharp. Several related results and open problems are provided. © 2007 Wiley Periodicals, Inc. J Graph Theory 56: 113–127, 2007
Synthesis of carbon‐14‐labeled isotopomer of 6‐(4‐methanesulfonylphenyl)‐5‐[4‐(2‐piperidin‐1‐yl‐ethoxy)phenoxy]‐naphthalen‐2‐ol HCL salt (LY2066948‐[14C] HCL salt)
Authors: Kuo Fengjiun , Clodfelter Dean K. , Priest Tamara R.
Published: June 2007

Carbon‐14‐labeled 6‐(4‐methanesulfonylphenyl)‐5‐[4‐(2‐piperidin‐1‐yl‐ethoxy)phenoxy]naphthalen‐2‐ol, a novel selective estrogen receptor modulator (SERM) was synthesized. The key component, 6‐methoxy‐1‐tetralone‐[carbonyl‐14C], was synthesized from 3‐(3‐methoxyphenyl)‐propionic acid via an intra‐molecular Friedel–Crafts acylation of 4‐(3‐methoxyphenyl)butanoic acid‐[carboxy‐14C]. A palladium catalyzed alpha‐keto arylation of 6‐methoxy‐1‐tetralone with 4‐methanesulfonyl‐phenyl bromide, followed by a sequence of bromination, DDQ dehydrogenation, aryl Ullmann reaction, and demethylation with BBr3 gave the desired product LY2066948‐[14C]. Copyright © 2007 John Wiley & Sons, Ltd.
Mid-infrared radiation spatial profile delivered by COP/Ag hollow glass waveguide
Authors: Němec M , Jelínková H , Fibrich M , Koranda P , Miyagi M , Iwai K , Shi Y-W , Matsuura Y
Published: June 2007

The modification of mid-infrared radiation spatial profile caused by COP/Ag hollow glass waveguide was investigated. The four laser systems – flashlamp pumped Er:YAG, Tm:YAG, and diode pumped Tm:YAG, and Tm:YAP laser sources – generating radiation in free-running regime were designed and constructed. The cyclic olefin polymer-coated silver hollow glass waveguide having an inner diameter of 700 μm and length up to 1.3 m was used as a delivery system base. The changes of beam spatial structures through the transfer system are presented. For Er:YAG laser the waveguide system was also investigated for bent cases. The energy transmission characteristics were measured for all systems.
Comparative study of photodegradation of three hematoporphyrin derivative: Photofrin®, Photogem®, and Photosan®
Authors: Ferreira J , Menezes P F C , Kurachi C , Sibata C H , Allison R R , Bagnato V S
Published: June 2007

We report the photodegradation of the three different photosensitizers derived from hematoporphyrin. In this paper we use the term phototransformation for describing the photodegradation or photobleaching process. This photodegradation alters the fluorescence during illumination. The rate of fluorescence variation was normalized to the solution absorption and the photon energy, resulting in the determination of the necessary number of photons to be absorbed to induce photosensitizer phototransformation. The parameter for rate of the molecules decay, the photon fluence rate and optical properties of the solution, allow us to determine the photosensitizer stability in solution during illumination. The results show that the order of susceptibility for phototransformation rate is: Photofrin® ≅ Photogem® < Photosan®. This difference in the phototransformation rate for Photosan® can be explained by the high proportion of aggregates in solution that inhibit the photo-oxidative process that impede the singlet oxygen formation. We hypothesize that there is a correlation between phototransformation rate and photodynamic efficacy witch is governed by singlet oxygen formation responsible by most relevant reaction for the photodynamic induction of cell death.
Laser frequency stabilization using selective reflection from a vapor cell with a half-wavelength thickness
Authors: Gazazyan E A , Papoyan A V , Sarkisyan D , Weis A
Published: June 2007

We have experimentally studied the selective reflection spectra of a circularly-polarized laser beam from a sub-micrometric Rb vapor cell with a thickness L around λ/2 (λ = 780 nm being the laser wavelength tuned to the D2line) in the presence of a longitudinal magnetic field. Based on the results of these studies, we propose a new method for the tunable locking of the diode laser frequency, which does not require frequency modulation nor complex electronics. The experimental realization of the technique has demonstrated its effectiveness and its competitiveness with the known DAVVL-type methods.
Interaction of Polyelectrolytes with Proteins, 3
Authors: Shalova Irina N. , Naletova Irina N. , Saso Luciano , Muronetz Vladimir I. , Izumrudov Vladimir A.
Published: June 2007

The ability of quaternized polyamines (poly‐N‐alkyl‐4‐vinylpyridinium bromides possessing a number, m, of methylene groups in the N‐alkyl substituent or a degree of alkylation, β, and n,n‐ionene bromides) to suppress the thermoaggregation of glyceraldehyde‐3‐phosphate dehydrogenase increased in the order m = 1 < 3 < 5, β = 95 < 85 < 70 $\ll$ 45 < 35 < 20 and n = 3 < 6 < 10, which agrees well with the increase, in the same order, in the hydrophobicity of the chains. Complexing suppressed thermoaggregation, but not thermodenaturation of the enzyme, which was even encouraged by the polycations and occurred at room temperature when the most efficient suppressor (with β = 20) was used. The adverse effect was reduced by the addition of sodium chloride which destroyed the complex and resulted in a noticeable reactivation.

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New Polymeric Materials with Interferential Optical Properties
Authors: Ghannam Leïla , Garay Hélène , François Jeanne , Billon Laurent
Published: June 2007

Nature provides a wide pallet of colors but also a wide number of fascinating optical phenomena such as nacre or interferential effects, which can be observed in insect wings and shellfish. The origin of such effects is attributed to the presence of highly ordered arrangements in Nature's materials. The aim of this paper is to focus some new approaches and advances for creating interferential optical phenomena as observed in nature by tuning or modeling the polymer architectures or organization.

A relatively simple method is described to prepare organic/inorganic hybrid pigments constituted of mica platelets and adsorbed polymer layers. It is shown that the color of mica is changed upon polymer adsorption, and when one of the copolymer sequences includes a dye, its color is influenced by the chemical properties of the mica surface. Moreover, a new facile route is presented to obtain highly ordered surfaces using ionomer macromolecular designs synthesized in one step by controlled radical polymerization. The preparation of films with very regular pore size and spatial organization is successfully realized by using ionomer solutions. An original property of these films with an iridescent color obtained by light diffraction as a result of the optical interferences of sunlight with the periodic honeycomb structures is presented.

All these new materials based on polymeric controlled structures can reproduce nature by creating an optical interferential and iridescent material, which offers new fascinating applications as original bio‐mimetic materials on inorganic surfaces.

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Price rigidity and flexibility: recent theoretical developments
Authors: Levy Daniel
Published: June 2007

The price system, the adjustment of prices to changes in market conditions, is the primary mechanism by which markets function and by which the three most basic questions get answered: what to produce, how much to produce and for whom to produce. To the behaviour of price and price system, therefore, have fundamental implications for many key issues in microeconomics and industrial organization, as well as in macroeconomics and monetary economics. In microeconomics, managerial economics, and industrial organization, economists focus on the price system efficiency. In macroeconomics and monetary economics, economists focus on the extent to which nominal prices fail to adjust to changes in market conditions. Nominal price rigidities play a particularly important role in modern monetary economics and in the conduct of monetary policy because of their ability to explain short‐run monetary non‐neutrality. The behaviour of prices, and in particular the extent of their rigidity and flexibility, therefore, is of central importance in economics. This introductory essay briefly summarizes the eight studies of price rigidity that are included in this special issue. Copyright © 2007 John Wiley & Sons, Ltd.
Classical and nonclassical symmetries for a Kuramoto–Sivashinsky equation with dispersive effects
Authors: Bruzón M. S. , Gandarias M. L. , Camacho J. C.
Published: June 2007

We apply the Lie‐group formalism and the nonclassical method due to Bluman and Cole to deduce symmetries of the generalized Kuramoto–Sivashinsky equation with dispersive effects. We make a full analysis of the symmetry reductions and we prove that the nonclassical method applied to the equation leads to new reductions, which cannot be obtained by Lie classical symmetries. Some new solutions can be derived. Copyright © 2007 John Wiley & Sons, Ltd.
Antigenotoxic effects of the phytoestrogen pelargonidin chloride and the polyphenol chlorogenic acid
Authors: Abraham Suresh K. , Schupp Nicole , Schmid Ursula , Stopper Helga
Published: June 2007

Pelargonidin (PEL), a common anthocyanidin with estrogenic activity, was tested in HL‐60 cells for its genotoxicity and possible antigenotoxic effects against 4‐nitroquinoline 1‐oxide (NQO), a potent mutagen and carcinogen which induces oxidative stress. To take into account potential interactions between phytochemicals within normal human nutrition, we evaluated a combination of PEL with the nonestrogenic phytochemical chlorogenic acid (CLA), one of the most abundant polyphenols in the human diet. PEL (⪇2 μM) and CLA (⪇800 μM) were nongenotoxic in the micronucleus test. We observed significant antigenotoxic effects against NQO with both compounds, but no additive interaction of PEL and CLA. Comet assay results showed a nonsignificant reduction in NQO‐induced DNA damage with both compounds and their combination. Flow cytometric analysis of oxidative stress revealed significant protection against NQO‐induced oxidative stress by PEL, CLA, and their combination. Furthermore, PEL and CLA prevented the NQO‐induced reduction in GSH level. This could be a mechanism for the observed reduction in genotoxicity. In conclusion, the phytoestrogen PEL revealed antioxidative and antigenotoxic properties in HL‐60 cells, but no significant additive interaction with the abundant nutritional polyphenol CLA under the tested conditions.
In vitro and in vivo metabolism of the soy isoflavone glycitein
Authors: Rüfer Corinna E. , Maul Ronald , Donauer Eva , Fabian Eric J. , Kulling Sabine E.
Published: June 2007

Glycitein (GLY) is a major isoflavone of soy germ which is used as a functional ingredient to enrich foods with isoflavones as well as a component of soy supplements. Since data on the metabolism of GLY are incomplete, the in vitro phase I metabolism of GLY using rat liver microsomes, human liver microsomes (HLM), as well as human fecal flora was investigated. Furthermore, the in vivo metabolism has been studied after administration of GLY to Sprague–Dawley rats. The identification of the formed metabolites has been elucidated using HPLC/DAD, HPLC/API‐ES MS, GC/MS, as well as reference compounds. With respect to the phase I metabolism, GLY has been converted to ten metabolites by liver microsomes of Aroclor‐induced Wistar rats with 8‐hydroxy(OH)‐GLY as the main metabolite. HLM converted GLY to six metabolites with 8‐OH‐GLY and 6‐OH‐daidzein (DAI) being the major products. No sex‐related differences were observed in each system. Intestinal metabolism of GLY led to four metabolites with 6‐OH‐DAI as the main product. The in vivo metabolism in rat urine after single‐dose administration of GLY resulted in the identification of three oxidative and two bacterial metabolites as well as the demethylation product 6‐OH‐DAI as the main metabolite.
Helical and random coil conformations of N‐propargylamide polymer and copolymers
Authors: Deng Jianping , Chen Bo , Zhang Zhigang , Yang Wantai
Published: June 2007

An N‐propargylamide monomer, CHCCH2NHCOC(CH3)2CH2CH3 (monomer 9), was polymerized in the presence of (nbd)Rh+B−(C6H5)4 (nbd represents norbornadiene) in CH2Cl2, CHCl3, tetrahydrofuran or dimethylformamide, to provide polymers with moderate number‐average molecular weights (Mn = 8700–12 100 g mol−1) in high yields (≥92%). The resulting poly(N‐propargylamide) (polymer 9) dissolves almost completely in CHCl3 (>95%). According to the UV‐visible spectra, measured at various temperatures, polymer 9 forms relatively stable helices over a wide temperature range (35–65 °C). Moreover, it exhibits reversible conformational transitions from an ordered helix to a random coil. On copolymerization of monomer 9 with CHCCH2NHCO(CH2)3CH3 (monomer 4) or CHCCH2NHCO(CH2)7CH3 (monomer 8), the solubility of polymer 9 improves noticeably. All the copolymers form helices under the experimental conditions. From the viewpoint of monomers 4 and 8, copolymerization with monomer 9 is favorable in terms of the copolymers forming helices. These findings reveal that the helical content and thermodynamic stability of the helices formed in the copolymers are likely to be controlled by selecting a suitable comonomer and by adjusting the composition of the copolymer. Copyright © 2007 Society of Chemical Industry
Pharmacological doses of dietary curcumin increase colon epithelial cell proliferation in vivo in rats
Authors: Kim Sylvia Jeewon , Hellerstein Marc K.
Published: June 2007

Although curcumin has preventive actions in animal models of colon cancer, whether the mechanism of action is through anti‐proliferation in normal environment is not clearly understood. Here, we studied the effects of chemopreventive doses of curcumin on the proliferation rate of colon epithelial cells (CEC), using a recently developed stable isotope – mass spectrometric method for measuring DNA synthesis rate. Adult male F344 rats were given diets containing 0, 2 and 4% curcumin for 5 weeks. 4% 2H2O was given in drinking water to label DNA, after a priming bolus, for 4 days prior to sacrifice. The isotopic enrichment of the deoxyribose moiety of deoxyadenosine from DNA was measured by gas chromatography – mass spectrometry. Cell cycle analysis was performed after propidium iodide staining of CECs. Curcumin administration did not reduce but instead resulted in dose‐dependent increases in CEC proliferation rate (p < 0.05) for 2% and 4% curcumin vs 0%). The length of the colon crypts and the fraction of cells in S‐phase were also increased in the 2% and 4% curcumin groups (p < 0.05). Thus, pharmacological doses of curcumin increase CEC proliferation rate and pool size in normal rats. Reduction of CEC proliferation therefore cannot explain the proposed chemopreventive actions of curcumin in colon cancer. Copyright © 2007 John Wiley & Sons, Ltd.
Thymoquinone decreases AGE‐induced NF‐κB activation in proximal tubular epithelial cells
Authors: Sayed Ahmed Amir Radwan , Morcos Michael
Published: June 2007

The inhibitory effects of thymoquinone (TQ) on activation of the redox‐sensitive transcription factor nuclear factor kappa B (NF‐κB) and interleukin‐6 (IL‐6) were studied in vitro. Human proximal tubular epithelial cells (pTECs) were cultivated and stimulated with advanced glycation end products (AGEs) and the effects of TQ were studied. A significant reduction of AGE‐induced NF‐κB‐activation and Il‐6 expression was observed. This points to potential antioxidative qualities of TQ. Copyright © 2007 John Wiley & Sons, Ltd.
Prophylaxis effect of Trigonella foenum graecum L. seeds on renal stone formation in rats
Authors: Laroubi Amine , Touhami Mohammed , Farouk Loubna , Zrara Ibtissam , Aboufatima Rachida , Benharref Ahmmed , Chait Abderrahman
Published: June 2007

Despite considerable progress in medical therapy, there is no satisfactory drug to treat kidney stones. Therefore, the current study aimed to look for an alternative by using Trigonella foenum graecum (Tfg) on nephrolithiasic rats as a preventive agent against the development of kidney stones, which is commonly used in Morocco as a phytotherapeutic agent. The inhibitory effect of the aqueous extract of Tfg seeds was examined on the formation of calcium oxalate renal stones induced by ethylene glycol (EG) with ammonium chloride. At the end of the experiment all kidneys were removed and examined microscopically for possible crystal/stone locations and the total calcium amount in the renal tissue was evaluated. The blood was recovered to determine the levels of calcium, phosphorus, creatinine and urea. The results showed that the amount of calcification in the kidneys and the total calcium amount of the renal tissue in rats treated with Tfg were significantly reduced compared with the untreated group. Consequently, Tfg may be a useful agent in the treatment of patients with calcic urolithiasis. Copyright © 2007 John Wiley & Sons, Ltd.
Effect of oriental herbal prescription Guan‐Xin‐Er‐Hao on coronary flow in healthy volunteers and antiapoptosis on myocardial ischemia‐reperfusion in rat models
Authors: Zhao Jianlei , Huang Xi , Tang Wenfu , Ren Ping , Xing Zhihua , Tian Xinqiao , Zhu Zhengyan , Wang Yonggang
Published: June 2007

Ischemic heart disease (IHD) is the main cause of death and a major public health problem in the world. The traditional herbal medicinal formula Guan‐Xin‐Er‐Hao (GXEH) has been used in China and East Asia for the treatment of coronary heart disease, however, the underlying cardioprotection mechanisms remain unclear. To make clear the antiischemic mechanism involved, GXEH was orally administered to 15 healthy volunteers. Heart rates (HR), blood pressure and coronary flow (CF) velocity before and 1 h after a single oral dose of GXEH were observed and compared. It was demonstrated that the oral administration of GXEH increased CF acutely in a dose‐dependent manner without modification of systemic hemodynamic parameters. Moreover, the myocardial protection function of GXEH was also experimentally examined in ischemia‐reperfusion (I/R) rat models. Apoptosis was measured quantitatively by the terminal transferase UTP nick end‐labeling (TUNEL) method and confirmed by caspase‐3 activity. The infarct size and TUNEL‐positive cells of GXEH‐treated group (20 g/kg) were reduced significantly, which was consistent with the decreased caspase‐3 activity. These suggest that GXEH protects hearts from ischemia injury by increasing CF and reduces infarct size by inhibiting myocardial apoptosis. Copyright © 2007 John Wiley & Sons, Ltd.
Modulation of postsynaptic potentials in rat cortical neurons by valerian extracts macerated with different alcohols: involvement of adenosine A1‐ and GABAA‐receptors
Authors: Sichardt K. , Vissiennon Z. , Koetter U. , Brattström A. , Nieber K.
Published: June 2007

Valeriana officinalis (valerian) is used traditionally as a mild sedative. Research into valerian is sparse, and studies differ greatly with respect to design, measures and preparations used. This study compares the action of a methanol (M‐E), ethanol (E‐E) and an extract macerated with ethylacetate (EA‐E) from roots of valerian (Valeriana officinalis L., Valerianaceae) on postsynaptic potentials (PSPs) in cortical neurons.

Intracellular recordings were performed in rat brain slice preparations containing pyramidal cells of the cingulate cortex. PSPs were induced by electrical field stimulation.

The M‐E induced strong inhibition in the concentration range 0.1–15 mg/mL, whereas the E‐E (1–10 mg/mL) did not influence significantly the PSPs. The maximum inhibition induced by the M‐E was completely antagonized by 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX, 0.1 µm), an antagonist on the adenosine A1 receptor. Contrary to the M‐E, the EA‐E (10 mg/mL) induced an increase of the PSPs, which was completely blocked by the GABAA receptor antagonist picrotoxin (100 µm).

The data suggest that activation of adenosine A1 and GABAA receptors is mediated by different components within the valerian extract. The two mechanisms may contribute independently to the sleep‐inducing effect of valerian. Copyright © 2007 John Wiley & Sons, Ltd.
Development of analytic energy gradient method in nuclear orbital plus molecular orbital theory
Authors: Hoshino Minoru , Tsukamoto Yasuhiro , Nakai Hiromi
Published: June 2007

This study formulates the analytic energy gradients in the Hartree‐Fock calculations of the NOMO theory, which simultaneously determines nuclear and electronic wave functions without the Born‐Oppenheimer approximation. The formulations correspond to the translation‐ and rotation‐contaminated (TRC), translation‐free (TF), and translation‐ and rotation‐free (TRF) treatments. The optimizations of the orbital centers for several diatomic molecules, which have been performed by using the analytic energy gradients, have given the averaged nuclear distances {R0} reflecting the quantum effects of nuclei and the anharmonicity of the potential energy surfaces. The numerical assessments have clarified that the effects of eliminating the translational and rotational contaminations, i.e., the TRF effects are important to improve the evaluations of {R0}, especially for the molecules including hydrogen atoms. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2007