bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of a Perfluorochemical Emulsion on the Rat Hepatic Mixed Function Oxidase System
Authors: Ravis William R , Ramakanth Swayampakula , Brzozowski Diane M , Hamrick Maynard E 
Published: April 2011

Abstract
The perfluorochemical components of synthetic oxygen transporting emulsions may persist in hepatic tissue. After a single 30% blood exchange with the perfluorochemical emulsion, Fluosol-DA 20%, the effects on the microsomal metabolism of 7-methoxycoumarin and 7-ethoxycoumarin were studied over a 9 week period. Fluosol-DA treated animals were compared with controls (sham) and hetastarch-treated controls. Changes in dealkylase activities were compared with induction by phenobarbitone and 3-methylcholanthrene. The liver to body weight ratio increased by 49% in Fluosol-DA-treated rats over the controls at 1 week and the microsomal protein was increased in the Fluosol-DA-treated rats after 4 and 9 weeks. Fluosol-DA treatment induced 7-methoxycoumarin demethylase with peak differences occurring at 1 week and a Vmax 75% greater than controls. Fluosol-DA was a more potent inducer of demethylase than phenobarbitone. In addition, 7-ethoxycoumarin de-ethylase was induced by Fluosol-DA with a peak induction at 4 weeks. The Vmax at 4 weeks in Fluosol-DA-treated rats was 122% greater than control. In this case, Fluosol-DA produced less induction in de-ethylase than 3-methylcholanthrene. These studies show that Fluosol-DA induces more than one form of cytochrome P450 and the effects resemble those of phenobarbitone more than those of 3-methylcholanthrene. Hetastarch, a plasma expander, did not affect liver weights, microsomal protein content, or the cytochrome P450 system.
Studies on an Oral Iron Chelator: 1,2-Dimethyl-3-hydroxy-pyrid-4-one (DMHP). Mechanism of Intestinal Absorption in Rabbits
Authors: Railkar Aruna M , Awni Walid M , Camp Richard J , Rahman Yueh-Erh 
Published: April 2011

Abstract
Over the last 30 years, desferrioxamine has been the only iron chelator in clinical use. This chelator is expensive and must be given by injection. A new class of chelators, namely 1-alkyl-2-methyl-3-hydroxypyrid-4-ones, have been shown to be orally effective. Using 1,2 dimethyl-3-hydroxy-pyrid-4-one (DMHP), we have carried out a study to clarify the mechanism of intestinal absorption of this new class of drug, using an in-situ system of the intestine from rabbit. The major site of DMHP absorption is in the intestine and is linear with increasing drug concentration. DMHP absorption per unit length of jejunum and ileum is similar; however, due to the larger surface area of jejunum, the absorption by ileum segment is more effective per unit surface. l-Proline, l-tryptophan (amino acids), 2-deoxyglucose, and sodium iodoacetate (metabolic inhibitors) have no effect on DMHP absorption, but l-phenylalanine, an amino acid with a 6-member carbon ring, significantly inhibits the DMHP absorption from the intestinal segment. We conclude that the mechanism of DMHP absorption in the intestine is mainly by simple passive diffusion based on the linear relationship found between drug concentration and absorption. However, the inhibitive effect of l-phenylalanine suggests that the co-existence of a facilitated uptake cannot be ruled out.
Accumulation of 5-Ethyl-2′-deoxyuridine and its 5,6-Dihydro Prodrugs in Murine Lung and its Potential Clinical Application
Authors: Cheraghali A Majid , Morin Kevin W , Kumar Rakesh , Knaus Edward E , Wiebe Leonard I 
Published: April 2011

Abstract
The accumulation of 5-ethyl-2′-deoxyuridine (EDU), (–)-trans-(5S, 6S)-5-bromo-5-ethyl-6-methoxy-5,6-dihydro-2′-deoxyuridine [(5S, 6S)-BMEDU], (+)-trans-(5R, 6R)-5-bromo-5-ethyl-6-methoxy-5,6-dihydro-2′-deoxyuridine [(5R, 6R)-BMEDU], (+)-trans-(5.R, 6R)-5-bromo-5-ethyl-6-ethoxy-5, 6-dihydro-2′-deoxyuridine (BEEDU), (+)-trans-(5R, 6R)-5-bromo-5-ethyl-6-ethoxy-5,6-dihydro-5′-O-valeryl-2′- deoxyuridine (VBEEDU) and (+)-trans-(5R, 6R)-5-bromo-5-ethyl-6-ethoxy-5,6-dihydro-3′-5′-di-O-valeryl-2′-deoxyuridine (DVBEEDU) in lung and other tissues was investigated in male Balb-C mice following intravenous injection of the corresponding 4-14C-labelled compounds.
EDU showed a rapid distribution into liver and lung immediately after injection, and the overall levels of radioactivity in blood, liver and lung were similar. The distribution of radioactivity in lung after injection of [4-14C](5S, 6S)-BMEDU and [4–14C](5R, 6R)-BMEDU were substantially different from one another and also from that of [4-14C]EDU. The radioactivity level present in lung samples after injection of both [4-14C](5S, 6S)-BMEDU and [4-14C](5R, 6R)-BMEDU was substantially higher than that in blood samples. Radioactivity levels present in lung samples taken at 18 min after injection of [4-14C]BEEDU were significantly higher (P &lt; 0·05) than those for liver and blood samples. Although the radioactivity present in lung samples after injection of [4-14C]VBEEDU was significantly higher (P &lt; 0·05) than those of liver and blood samples, [4-14C]VBEEDU did not provide a higher radioactivity level in lung samples than did [4-14C]BEEDU. The level of radioactivity in lung samples following injection of [4-14C]DVBEEDU was also higher than that of blood samples. EDU undergoes glycosidic bond cleavage to form EU in lung following intravenous injection into Balb-C mice.
The concentrations of EDU and 5-ethyluracil (EU) following intravenous injection of EDU, and its prodrugs BEEDU and VBEEDU, were quantitated in lung and blood samples. In contrast to lung samples, EU was not detected in blood samples at 120 min post injection of EDU. The concentrations of both EDU and EU in lung tissues after injection of BEEDU and VBEEDU were substantially higher than those in blood samples.
Pharmacological Profile of Rat Pleurisy Induced by Bothrops jararaca Venom
Authors: Búrigo A C , Calixto J B , Medeiros Y S 
Published: April 2011

Abstract
Bothrops jararaca venom (30 μg/site) triggered a marked inflammatory reaction in the pleural cavity that was long-lasting and reproducible.
In the first 1 h after pleurisy induction, a significant decrease of total and differential cell count was observed in comparison with control values, despite the gradual enhancement of fluid leakage. A significant increase of cell migration was observed after 3 h of pleurisy induction, due to mononuclear and neutrophil cells that peaked 8 h later and this was followed by a gradual decrease, remaining elevated up to 24 h. In parallel with cell influx, a significant increase of fluid leakage that peaked between 1 and 8 h was observed, being completely abolished after 12 h following pleurisy induction. This inflammatory response was not associated in parallel with significant changes in circulating leucocyte cells and it was significantly inhibited by compound 48/80, cyproheptadine, pyrilamine, dexamethasone, indomethacin and phenidone. Preheating of the venom (100C) caused a significant decrease of both leakage of fluid and cell migration in the pleural cavity 8 h after pleurisy induction. Previous exposure to the venom (30 μg/site, 5 days before) produced a significant decrease of both cell migration and fluid leakage 4 h after triggering pleurisy with the same dose of the venom. Otherwise, prior daily treatment with the venom (10 μg/site, 4 days) resulted only in marked fluid leakage reduction 1 h after treating the animals with BJV (30 μg/site).
These results show that the venom elicits pro-inflammatory effects in the rat pleural cavity which involve the participation of several mediators, including histamine, 5−hydroxytryptamine and products of arachidonic pathways.
Regioselectivity and Substrate Concentration-dependency of Involvement of the CYP2D Subfamily in Oxidative Metabolism of Amitriptyline and Nortriptyline in Rat Liver Microsomes
Authors: Masubuchi Yasuhiro , Iwasa Takashi , Fujita Shoichi , Suzuki Tokuji , Horie Toshiharu , Narimatsu Shizuo 
Published: April 2011

Abstract
Kinetic analysis of the metabolism of amitriptyline and nortriptyline using liver microsomes from Wistar rats showed that more than one enzyme was involved in each reaction except for monophasic amitriptyline N-demethylation. The Vmax values particularly in the high-affinity sites for E-10-hydroxylation of both drugs were larger than those for Z-10-hydroxylations. Their E- and Z-10-hydroxylase activities in Dark-Agouti rats, which are deficient for CYP2D1, were significantly lower than those in Wistar rats at a lower substrate concentration (5 μM). The strain difference was reduced at a higher substrate concentration (500 μM). A similar but a smaller strain difference was also observed in nortriptyline N-demethylase activity, and a pronounced sex difference (male &gt; female) was observed in N-demethylation of both drugs in Wistar and Dark-Agouti rats. The reactions with the strain difference were inhibited concentration-dependently by sparteine, a substrate of the CYP2D subfamily, and an antibody against a CYP2D isoenzyme. The profiles of these decreased metabolic activities corresponded to that of the lower metabolic activities in Dark-Agouti rats.
These results indicated that a cytochrome P450 isozyme in the CYP2D subfamily was involved in E- and Z- 10-hydroxylations of amitriptyline and nortriptyline in rat liver microsomes as a major isozyme in a low substrate concentration range. It seems likely that the CYP2D enzyme contributes to nortriptyline N-demethylation.
Potential Irreversible Ligands for Opioid Receptors. Cinnamoyl Derivatives of β-Naltrexamine
Authors: Derrick Ian , Lewis John W , Moynihan Humphrey A , Broadbear Jillian , Woods James H 
Published: April 2011

Abstract
Cinnamoyl derivatives of β-naltrexamine (β-NTA) have been prepared and evaluated as potential irreversible opioid antagonists.
In receptor binding assays, isolated tissue preparations and mouse antinociception assays the p-methylcinnamoyl derivative BU42 was similar to the standard opioid ligand β-funaltrexamine (β-FNA). The main features were reversible κ agonism and irreversible μ antagonism. Surprisingly the p-chlorocinnamoyl derivative BU59 showed only modest competitive antagonist activity in-vivo despite appearing to bind irreversibly to μ receptors in the guinea-pig ileum (GPI) preparation. BU60, the dihydrocinnamoyl analogue of BU59, like BU59 displayed reversible κ agonism in GPI but in mouse antinociception assays its agonism was mediated by κ and β receptors rather than κ.
The surprising changes of profile attributable to substitution in the aromatic ring of the cinnamoylamido group in this small series suggests that a larger range of substituted cinnamoylamido derivatives should be studied to further elucidate the effects of Michael acceptor activity and other factors.
Knowledge, attitude and practices of Qatari patients with type 2 diabetes mellitus
Authors: Kheir Nadir , Greer William , Yousif Adil , Al Geed Hajer , Al Okkah Randa 
Published: April 2011

Abstract

Objectives
Patient compliance with their medications and their ability for self-management in type 2 diabetes mellitus (T2DM) is a growing cause of concern to healthcare providers. Knowledge about diabetes, attitude towards the condition and time management with respect to the condition (practice), collectively known as KAP, are known to affect compliance and play an important part in diabetes management. We aimed to describe the knowledge, attitude, practice and psychological status of adult Qatari patients with T2DM, and to explore the interaction between these and other patient-related factors which could impact on the ability of the patients to manage their diabetes and to achieve desirable health outcomes.

Methods
A questionnaire (the Diabetes Habits and Beliefs Questionnaire, DHBQ) was used to investigate the level and relationship between knowledge, attitude, general practice and psychological status of patients with T2DM. The data was collected in face-to-face interviews with patients visiting the diabetic clinic at a tertiary hospital in Qatar during the period January 2008 to March 2009.

Key findings
There were significant differences in attitude and knowledge between educational levels. Knowledge and attitude were highly correlated and the psychological status of the patient was positively associated with both knowledge and attitude. There was generally poor practice of regularly inspecting feet to detect signs of neuropathy, taking medication in relation to meals, modifying doses when necessary and setting goals for therapy.

Conclusions
The data provided can assist pharmacists and other healthcare practitioners in tailoring educational programmes aimed at improving diabetes control.
A combined Fuzzy and Naïve Bayesian strategy can be used to assign event codes to injury narratives
Authors: Marucci-Wellman H , Lehto M , Corns H 
Published: April 2011

BackgroundBayesian methods show promise for classifying injury narratives from large administrative datasets into cause groups. This study examined a combined approach where two Bayesian models (Fuzzy and Naïve) were used to either classify a narrative or select it for manual review.MethodsInjury narratives were extracted from claims filed with a worker's compensation insurance provider between January 2002 and December 2004. Narratives were separated into a training set (n=11,000) and prediction set (n=3,000). Expert coders assigned two-digit Bureau of Labor Statistics Occupational Injury and Illness Classification event codes to each narrative. Fuzzy and Naïve Bayesian models were developed using manually classified cases in the training set. Two semi-automatic machine coding strategies were evaluated. The first strategy assigned cases for manual review if the Fuzzy and Naïve models disagreed on the classification. The second strategy selected additional cases for manual review from the Agree dataset using prediction strength to reach a level of 50% computer coding and 50% manual coding.ResultsWhen agreement alone was used as the filtering strategy, the majority were coded by the computer (n=1,928, 64%) leaving 36% for manual review. The overall combined (human plus computer) sensitivity was 0.90 and positive predictive value (PPV) was >0.90 for 11 of 18 2-digit event categories. Implementing the 2nd strategy improved results with an overall sensitivity of 0.95 and PPV >0.90 for 17 of 18 categories.ConclusionsA combined Naïve-Fuzzy Bayesian approach can classify some narratives with high accuracy and identify others most beneficial for manual review, reducing the burden on human coders.
DISCRETE SYMMETRY AND STABILITY IN HAMILTONIAN DYNAMICS
Authors: BOUNTIS TASSOS , CHECHIN GEORGE , SAKHNENKO VLADIMIR 
Published: April 2011

In the present tutorial we address a problem with a long history, which remains of great interest to date due to its many important applications: It concerns the existence and stability of periodic and quasiperiodic orbits in N-degree of freedom Hamiltonian systems and their connection with discrete symmetries. Of primary importance in our study is what we call nonlinear normal modes (NNMs), i.e. periodic solutions which represent continuations of the system's linear normal modes in the nonlinear regime. We examine questions concerning the existence of such solutions and discuss different methods for constructing them and studying their stability under fixed and periodic boundary conditions. In the periodic case, we find it particularly useful to approach the problem through the discrete symmetries of many models, employing group theoretical concepts to identify a special type of NNMs which we call one-dimensional "bushes". We then describe how to use linear combinations of s ≥ 2 such NNMs to construct s-dimensional bushes of quasiperiodic orbits, for a wide variety of Hamiltonian systems including particle chains, a square molecule and octahedral crystals in 1, 2 and 3 dimensions. Next, we exploit the symmetries of the linearized equations of motion about these bushes to demonstrate how they may be simplified to study the destabilization of these orbits, as a result of their interaction with NNMs not belonging to the same bush. Applying this theory to the famous Fermi Pasta Ulam (FPU) chain, we review a number of interesting results concerning the stability of NNMs and higher-dimensional bushes, which have appeared in the recent literature. We then turn to a newly developed approach to the analytical and numerical construction of quasiperiodic orbits, which does not depend on the symmetries or boundary conditions of our system. Using this approach, we demonstrate that the well-known "paradox" of FPU recurrences may in fact be explained in terms of the exponential localization of the energies Eq of NNM's being excited at the low part of the frequency spectrum, i.e. q = 1, 2, 3, …. These results indicate that it is the stability of these low-dimensional compact manifolds called q-tori, that is related to the persistence or FPU recurrences at low energies. Finally, we discuss a novel approach to the stability of orbits of conservative systems, expressed by a spectrum of indices called GALI k, k = 2, …, 2N, by means of which one can determine accurately and efficiently the destabilization of q-tori, leading, after very long times, to the breakdown of recurrences and, ultimately, to the equipartition of energy, at high enough values of the total energy E.
MULTIVALUED GENERALIZATIONS OF THE FRANKL–PACH THEOREM
Authors: HEGEDŰS GÁBOR , RÓNYAI LAJOS 
Published: April 2011

In [On disjointly representable sets, Combinatorica4 (1984) 39–45] Frankl and Pach proved the following uniform version of Sauer's lemma. Let n,d,s be natural numbers such thatd ≤ n, s + 1 ≤ n/2. Let [Formula: see text] be an arbitrary d-uniform set system such that [Formula: see text] does not shatter an s + 1-element set, then[Formula: see text] We prove here two generalizations of the above theorem to n-tuple systems. To obtain these results, we use Gröbner basis methods, and describe the standard monomials of Hamming spheres.
ATTRACTOR FLOWS IN st2 BLACK HOLES
Authors: ROYCHOWDHURY RAJU 
Published: April 2011

Following the same treatment of Bellucci et al. we obtain, the hitherto unknown general solutions of the radial attractor flow equations for extremal black holes, both for non-BPS with non-vanishing and vanishing central charge Z for the so-called st2 model, the minimal rank-two [Formula: see text] symmetric supergravity in d = 4 space-time dimensions. We also make useful comparisons with results that already exist in literature, and introduce the fake supergravity (first-order) formalism to be used in our analysis. An analysis of the BPS bound all along the non-BPS attractor flows and of the marginal stability of corresponding D-brane charge configurations has also been presented.
LIN28B Polymorphisms Influence Susceptibility to Epithelial Ovarian Cancer
Authors: Permuth-Wey Jennifer , Kim Donghwa , Tsai Ya-Yu , Lin Hui-Yi , Chen Y. Ann , Barnholtz-Sloan Jill , Birrer Michael J. , Bloom Gregory , Chanock Stephen J. , Chen Zhihua , Cramer Daniel W. , Cunningham Julie M. , Dagne Getachew , Ebbert-Syfrett Judith , Fenstermacher David , Fridley Brooke L. , Garcia-Closas Montserrat , Gayther Simon A. , Ge William , Gentry-Maharaj Aleksandra , Gonzalez-Bosquet Jesus , Goode Ellen L. , Iversen Edwin , Jim Heather , Kong William , McLaughlin John , Menon Usha , Monteiro Alvaro N.A. , Narod Steven A. , Pharoah Paul D.P. , Phelan Catherine M. , Qu Xiaotao , Ramus Susan J. , Risch Harvey , Schildkraut Joellen M. , Song Honglin , Stockwell Heather , Sutphen Rebecca , Terry Kathryn L. , Tyrer Jonathan , Vierkant Robert A. , Wentzensen Nicolas , Lancaster Johnathan M. , Cheng Jin Q. , Sellers Thomas A. ,   on behalf of the Ovarian Cancer Association Consortium (OCAC)
Published: April 2011

Abstract
Defective microRNA (miRNA) biogenesis contributes to the development and progression of epithelial ovarian cancer (EOC). In this study, we examined the hypothesis that single nucleotide polymorphisms (SNP) in miRNA biogenesis genes may influence EOC risk. In an initial investigation, 318 SNPs in 18 genes were evaluated among 1,815 EOC cases and 1,900 controls, followed up by a replicative joint meta-analysis of data from an additional 2,172 cases and 3,052 controls. Of 23 SNPs from 9 genes associated with risk (empirical P &lt; 0.05) in the initial investigation, the meta-analysis replicated 6 SNPs from the DROSHA, FMR1, LIN28, and LIN28B genes, including rs12194974 (G&gt;A), an SNP in a putative transcription factor binding site in the LIN28B promoter region (summary OR = 0.90, 95% CI: 0.82–0.98; P = 0.015) which has been recently implicated in age of menarche and other phenotypes. Consistent with reports that LIN28B overexpression in EOC contributes to tumorigenesis by repressing tumor suppressor let-7 expression, we provide data from luciferase reporter assays and quantitative RT-PCR to suggest that the inverse association among rs12194974 A allele carriers may be because of reduced LIN28B expression. Our findings suggest that variants in LIN28B and possibly other miRNA biogenesis genes may influence EOC susceptibility. Cancer Res; 71(11); 3896–903. ©2011 AACR.
CD24 Offers a Therapeutic Target for Control of Bladder Cancer Metastasis Based on a Requirement for Lung Colonization
Authors: Overdevest Jonathan B. , Thomas Shibu , Kristiansen Glen , Hansel Donna E. , Smith Steven C. , Theodorescu Dan 
Published: April 2011

AbstractMetastasis is lethal in most bladder cancer patients. Expression of CD24, a glycosyl phosphatidylinositol (GPI)-linked sialoglycoprotein and cancer stem cell marker, is associated with metastatic progression in multiple cancer types, yet the role of CD24 in this process remains unclear. While developing a murine model of human metastatic bladder cancer, we observed that tumor cell CD24 expression correlated with a propensity to metastasize to the lung. Our immunohistochemical evaluation of 60 paired primary and metastatic human bladder cancer samples revealed increased intensity (P &lt; 0.001) and frequency (P &lt; 0.001) of CD24 expression in metastases. To directly evaluate the role of CD24 in metastatic colonization, we manipulated CD24 expression in human bladder cancer cell lines using short hairpin RNA depletion, cDNA overexpression, and fluorescence-activated cell sorting selection. Although suppression of CD24 reduced acute tumor cell retention in the lungs of mice inoculated intravenously with cancer cells, this differential retention was no longer apparent after 24 hours, prompting us to evaluate the role of CD24 in lung colonization. Here, CD24 was found necessary for subsequent development of lung metastases. We next treated clinically detectable lung metastases in mice with anti-CD24 antibody and observed reduced tumor growth and prolonged survival. These findings suggest that CD24 is a lynchpin of metastatic progression and a promising therapeutic target for antimetastatic therapy. Cancer Res; 71(11); 3802–11. ©2011 AACR.