bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of intraplaque hemorrhage in atherothrombosis evolution via neutrophil protease enrichment
Authors: Leclercq Anne , Houard Xavier , Philippe Monique , Ollivier Véronique , Sebbag Uriel , Meilhac Olivier , Michel Jean-Baptiste 
Published: September 2007

AbstractThe pathological remodeling of the arterial wall in atherosclerosis involves protease activities, which play a major role in complications via plaque rupture. Circulating leukocytes and particularly neutrophils have been shown to be an independent predictor of recurrent ischemic events. However, neutrophils are poorly documented within atherosclerotic plaques. We hypothesized that intraplaque hemorrhage could convey neutrophils into the lesion, spreading into the necrotic core, thus participating in its protease enrichment. One hundred human carotid endarterectomy specimens were dissected into culprit-stenosing plaques (CPs) and adjacent noncomplicated plaques. Half of CPs exhibited hemorrhage, which was confirmed by the release of hemoglobin. Pro- and active forms of matrix metalloproteinase-9 (MMP-9) were increased in media conditioned by hemorrhagic plaques. Higher levels of lipocalin [neutrophil gelatinase-associated lipocalin (NGAL)]/MMP-9 complexes, specifically released by neutrophils, were also found in conditioned media from plaques with hemorrhage. Immunohistochemical analysis of the corresponding carotid samples showed that neutrophil markers such as elastase, NGAL/MMP-9, CD66b, and proteinase 3 colocalized with blood constituents (i.e., hemoglobin, plasminogen). All markers of neutrophil degranulation were positively correlated in CP-conditioned media (α1-antitrypsin/elastase complexes, myeloperoxidase, and α-defensins), and higher levels came from CPs containing intraplaque hemorrhages. Addition of an elastase inhibitor at the time of incubation led to a decrease in the proMMP-9 activation in CPs, suggesting cross-talk between proteases released by neutrophils. Finally, we found that neovessels observed at the interface between cap and core exhibit an activated endothelium, which may favor leukocyte diapedesis. Our study thus provides evidence for the involvement of neutrophils in plaque vulnerability.
Prediction of human pharmacokinetics – evaluation of methods for prediction of volume of distribution
Authors: Fagerholm Urban 
Published: September 2007

AbstractThe aim was to evaluate and review methods for prediction of the steady-state volume of distribution (VD,ss) of xenobiotics in man. For allometry, ˜30–40% of predictions are classified as incorrect, humans and animals belong to different VD,ss categories for ˜30% of the compounds, maximum prediction errors are large (&gt;10-fold), the b-exponent ranges between −0.2 and 2.2 (averaging ˜0.8–0.9), and &gt;2-fold prediction errors are found for 35% of the substances. The performance is consistent with species differences of binding in and outside the vasculature. The largest errors could potentially lead to very poor prediction of exposure profile and failure in clinical studies. A re-evaluation of allometric scaling of unbound tissue volume of distribution demonstrates that this method is less accurate (27% of predictions &gt;2-fold errors) than a previous evaluation demonstrated. By adding molecular descriptor information, predictions based on animal VD,ss data can be improved. Improved predictions (˜1/10 of allometric errors) can also be obtained by using the relationship between unbound fraction in plasma (fu,pl) and VD,ss for each substance (method suggested by the author). A physiologically-based 4-compartment model (plasma, red blood cells, interstitial fluid and cell volume) together with measured tissue-plasma partitioning coefficients in rats, fu,pl, interstitial-plasma concentration ratio of albumin, organ weight and blood flow data has been successfully applied. Prediction errors for one basic and one neutral drug are only 3–5%. The data obtained with this comparably laboratory-intensive method are limited to these two compounds. A similar approach where predicted tissue partitioning is used, and a computational model, give prediction errors similar to that of allometry. Advantages with these are the suitability for screening and avoidance of animal experiments. The evaluated methods do not account for potential active transport and slow dissociation rates.
Polymeric drug based on sulfanilamide: synthesis, antimicrobial and drug releasing studies
Authors: Reddy C Umamaheswara , Amalraj A , Reddy B S R , Arun A 
Published: September 2007

Abstract
N-((4-amino sulfonyl)phenyl)acrylamide (APA) was synthesized using sulfanilamide and acryloyl chloride in the presence of triethyl amine at 0–5°C. Homo- and co-polymerization of 2-hydroxyethyl acrylate (HEA) and acrylic acid (AA) were done by adopting a solution polymerization technique using methyl ethyl ketone (MEK) as a solvent and benzoyl peroxide (BPO) as a free radical initiator at 70+1°C. All the monomers and polymers were characterized by IR and NMR techniques. These monomers and polymers were tested for their antimicrobial activity against five different ATCC strain microorganisms (Escherichia coli (25922), Pseudomonas aeruginosa (27853), Klebsiella (70063), Salmonella typhi (6539) and Staphylococcus aureus (25923)). The effect of co-monomer, other than the active drug moiety present in the polymeric drug, is discussed. The antimicrobial activity of APA on Gram-positive bacteria was enhanced when copolymerized with AA and HEA. The polymer was made into a film form and that film was used for drug releasing study. The drug releasing rate was monitored by the absorption at 268 nm using a UV spectrophotometer. The effect of pH and the temperature on the drug releasing rate was monitored and found that the releasing rate was dependent on the co-monomer, pH and temperature of the medium.
Biotransformation and mass balance of tipranavir, a nonpeptidic protease inhibitor, when co-administered with ritonavir in Sprague-Dawley rats
Authors: Macha Sreeraj , Chen Linzhi , Norris Stephen H , Philip Elsy , Mao Yanping , Silverstein Helga , Struble Craig , Beers Wendy 
Published: September 2007

AbstractIn this study, tipranavir (TPV) biotransformation and disposition when co-administered with ritonavir (RTV) were characterized in Sprague–Dawley rats. Rats were administered a single intravenous (5 mg kg−1) or oral (10 mg kg−1) dose of [14C]TPV with co-administration of RTV (10 mg kg−1). Blood, urine, faeces and bile samples were collected at specified time-points over a period of 168 h. Absorption of TPV-related radioactivity ranged from 53.2–59.6%. Faecal excretion was on average 86.7% and 82.4% (intravenous) and 75.0% and 82.0% (oral) of dosed radioactivity in males and females, respectively. Urinary excretion was on average 4.06% and 6.73% (intravenous) and 9.71% and 8.28% (oral) of dosed radioactivity in males and females, respectively. In bile-duct-cannulated rats, 39.8% of the dose was recovered in bile. After oral administration, unchanged TPV accounted for the majority of the radioactivity in plasma (85.7–96.3%), faeces (71.8–80.1%) and urine (33.3–62.3%). The most abundant metabolite in faeces was an oxidation metabolite R-2 (5.9–7.4% of faecal radioactivity, 4.4–6.1% of dose). In urine, no single metabolite was found to be significant, and comprised &lt;1% of dose. TPV when co-administered with RTV to rats was mainly excreted in feces via bile and the parent compound was the major component in plasma and faeces.
Effect of a leukotriene inhibitor (MK886) on nitric oxide and hydrogen peroxide production by macrophages of acutely and chronically stressed mice
Authors: Sforcin José Maurício , Nunes Gladston A , Missima Fabiane , Sá-Nunes Anderson , Faccioli Lúcia H 
Published: September 2007

Abstract
We evaluated the effect of a leukotriene inhibitor (MK886) on nitric oxide (NO) and hydrogen peroxide (H2O2) production by peritoneal macrophages of mice subjected to acute and chronic stress. Acute stress was induced by keeping mice immobilized in a tube for 2 h. Chronic stress was induced over a 7-day period by the same method, but with increasing duration of immobilization. The effects of MK886 were investigated in-vitro after incubation with peritoneal macrophages, and in-vivo by submitting mice to stress and treating them daily with MK886. Supernatants of macrophage cultures were collected for NO determination and adherent cells were used for H2O2 determination. Macrophages from mice submitted to acute or chronic stress showed no alterations in H2O2 production. However, macrophages of acutely and chronically stressed mice showed inhibition of NO after incubation with MK886 in-vitro. Administration of MK886 to chronically stressed mice increased generation of H2O2 and inhibited production of NO. Our data suggest an important role of leukotrienes in NO synthesis, which is important in controlling replication of several infectious agents, mainly in stressed and immunosuppressed animals.
Role of intestinal efflux transporters in the intestinal absorption of methotrexate in rats
Authors: Yokooji Tomoharu , Yumoto Ryoko , Nagai Junya , Takano Mikihisa , Yokooji Tomoharu , Murakami Teruo 
Published: September 2007

AbstractThe role of intestinal efflux transporters such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins (MRPs) in intestinal absorption of methotrexate was examined in rats. In everted intestine, the mucosal efflux of methotrexate after application to serosal side was higher in jejunum than ileum, and the efflux in jejunum was suppressed by pantoprazole, a BCRP inhibitor, and probenecid, an MRP inhibitor, but not by verapamil, a P-gp inhibitor. The mucosal methotrexate efflux in ileum was suppressed by pantoprazole, but not by other inhibitors. On the other hand, the serosal efflux of methotrexate after application to mucosal side was greater in ileum than jejunum, and was suppressed by probenecid. In in-vivo rat studies, the intestinal absorption of methotrexate was significantly higher when methotrexate was administered to ileum than jejunum. Pantoprazole increased methotrexate absorption from jejunum and ileum. Probenecid increased the absorption of methotrexate from jejunum but decreased the absorption from ileum, as evaluated by peak plasma methotrexate levels. In conclusion, BCRP and MRPs are involved in the regional difference in absorption of methotrexate along the intestine, depending on their expression sites.
Essential Role of Mitochondrial Function in Adiponectin Synthesis in Adipocytes
Authors: Koh Eun Hee , Park Joong-Yeol , Park Hye-Sun , Jeon Min Jae , Ryu Je Won , Kim Mina , Kim Sun Young , Kim Min-Seon , Kim Seung-Whan , Park In Sun , Youn Jang Hyun , Lee Ki-Up 
Published: September 2007

OBJECTIVE—Adiponectin is an important adipocytokine that improves insulin action and reduces atherosclerotic processes. The plasma adiponectin level is paradoxically reduced in obese individuals, but the underlying mechanism is unknown. This study was undertaken to test the hypothesis that mitochondrial function is linked to adiponectin synthesis in adipocytes.
RESEARCH DESIGN AND METHODS—We examined the effects of rosiglitazone and the measures that increase or decrease mitochondrial function on adiponectin synthesis. We also examined the molecular mechanism by which changes in mitochondrial function affect adiponectin synthesis.
RESULTS—Adiponectin expression and mitochondrial content in adipose tissue were reduced in obese db/db mice, and these changes were reversed by the administration of rosiglitazone. In cultured adipocytes, induction of increased mitochondrial biogenesis (via adenoviral overexpression of nuclear respiratory factor-1) increased adiponectin synthesis, whereas impairment in mitochondrial function decreased it. Impaired mitochondrial function increased endoplasmic reticulum (ER) stress, and agents causing mitochondrial or ER stress reduced adiponectin transcription via activation of c-Jun NH2-terminal kinase (JNK) and consequent induction of activating transcription factor (ATF)3. Increased mitochondrial biogenesis reversed all of these changes.
CONCLUSIONS—Mitochondrial function is linked to adiponectin synthesis in adipocytes, and mitochondrial dysfunction in adipose tissue may explain decreased plasma adiponectin levels in obesity. Impaired mitochondrial function activates a series of mechanisms involving ER stress, JNK, and ATF3 to decrease adiponectin synthesis.
Studies in 3,523 Norwegians and Meta-Analysis in 11,571 Subjects Indicate That Variants in the Hepatocyte Nuclear Factor 4α (HNF4A) P2 Region Are Associated With Type 2 Diabetes in Scandinavians
Authors: Johansson Stefan , Ræder Helge , Eide Stig Å , Midthjell Kristian , Hveem Kristian , Søvik Oddmund , Molven Anders , Njølstad Pål Rasmus 
Published: September 2007

OBJECTIVE— Recent publications have found an association between common variants near the hepatocyte nuclear factor 4α (HNF4A) P2 promoter and type 2 diabetes in some populations but not in others, and the role for HNF4A in type 2 diabetes has remained unclear. In an attempt to address these inconsistencies, we investigated HNF4A single nucleotide polymorphisms (SNPs) in a large population-based sample and included a meta-analysis of published studies.
RESEARCH DESIGN AND METHODS— We genotyped 12 SNPs in the HNF4A region in a Norwegian population–based sample of 1,644 individuals with type 2 diabetes and 1,879 control subjects (the Nord-Trøndelag Health Study [HUNT] 2). We combined our data with all previously published case/control studies and performed a meta-analysis.
RESULTS— Consistent with initial studies, we found a trend toward association for the SNPs rs1884613 (odds ratio [OR] 1.17 [95% CI 1.03–1.35]) and rs2144908 (1.21 [1.05–1.38]) in the P2 region and for rs4812831 (1.21 [1.02–1.44]), located 34 kb downstream of the P2 promoter. Meta-analysis, comprising 12,292 type 2 diabetic case and 15,519 control subjects, revealed a nonsignificant OR of 1.05 (95% CI 0.98–1.12) but with significant heterogeneity between the populations. We therefore performed a subanalysis including only the data for subjects from Scandinavia. Among the 4,000 case and 7,571 control Scandinavian subjects, a pooled OR of 1.14 (1.06–1.23), P = 0.0004, was found for the SNP rs1884613.
CONCLUSIONS— Our results suggest that variation in the HNF4A region is associated with type 2 diabetes in Scandinavians, highlighting the importance of exploring small genetic effects in large, homogenous populations.
Aberrant Endometrial Features of Pregnancy in Diabetic NOD Mice
Authors: Burke Suzanne D. , Dong Hongmei , Hazan Aleah D. , Croy B. Anne 
Published: September 2007

OBJECTIVE—Pregnant diabetic women are at a 4–12 times higher risk for preeclampsia, an urgent acute-onset complication of mid- to late gestation, than normal pregnant women. Hallmarks of preeclampsia are hypertension, proteinuria, and incomplete modification of endometrial spiral arteries. Transient proangiogenic lymphocytes called uterine natural killer (uNK) cells are implicated in human and rodent spiral artery modification. We studied mid- to late gestations in spontaneously type 1 diabetic NOD mice to investigate whether diabetes alters uNK cell homing and/or function.RESEARCH DESIGN AND METHODS—Normoglycemic, pre-diabetic, and diabetic NOD mice and controls were mated. Lymphocytes and endometrial endothelium and decidua were studied histologically and in functional assays.RESULTS—Conception accelerated progression to overt diabetes in NOD females who had limited spiral artery development, heavier placentas, and lighter fetuses displaying numerous birth defects compared with controls. UNK cell numbers were reduced in the decidua basalis of diabetic females, whereas interferon-γ production was elevated. In diabetic NOD mice, decidual expression of the mucosal vascular addressin cell adhesion molecule (MAdCAM)-1 was aberrant in position, whereas vascular cell adhesion molecule (VCAM)-1 expression was reduced. Assays of lymphocyte adhesion to tissue sections under shear forces indicated that diabetes compromises the potential homing functions of both endometrial endothelium and peripheral NK cells.CONCLUSIONS—In diabetes, gestational endometrium has immune and vascular defects that likely contribute to murine fetal loss and birth defects. Analogous problems and preeclampsia in diabetic women may involve similar mechanisms.
Nonisothermal crystallization kinetics and morphology of poly(ethylene terephthalate) modified with poly(lactic acid)
Authors: Acar Işıl , Durmuş Ali , Özgümüş Saadet 
Published: September 2007

AbstractThe nonisothermal crystallization kinetics of poly(ethylene terephthalate) (PET) copolymers modified with poly(lactic acid) (PLA) were investigated with differential scanning calorimetry, and a crystal morphology of the samples was observed with scanning electron microscopy. Waste PET (P100) obtained from postconsumer water bottles was modified with a low‐molecular‐weight PLA. The PET/PLA weight ratio was 90/10 (P90) or 50/50 (P50) in the modified samples. The nonisothermal melt‐crystallization kinetics of the modified samples were compared with those of P100. The segmented block copolymer structure (PET‐b‐PLA‐b‐PET) of the modified samples formed by a transesterification reaction between the PLA and PET units in solution and the length of the aliphatic and aromatic blocks were found to have a great effect on the nucleation mechanism and overall crystallization rate. On the basis of the results of the crystallization kinetics determined by several models (Ozawa, Avrami, Jeziorny, and Liu–Mo) and morphological observations, the crystallization rate of the samples decreased in the order of P50 > P90 > P100, depending on the amount of PLA in the copolymer structure. However, the apparent crystallization activation energies of the samples decreased in the order of P90 > P100 > P50. It was concluded that the nucleation rate and mechanism were affected significantly by the incorporation of PLA into the copolymer structure and that these also had an effect on the overall crystallization energy barrier. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Dose‐dependent pharmacokinetics of a new Na+/H+ exchanger inhibitor KR‐33028 in rats
Authors: Kim Young Hoon , Yoo Sun Dong , Kim You Sun , Lee Kyung Hee , Lee Hye Suk 
Published: September 2007

AbstractThe dose‐dependency of the pharmacokinetics of a new Na+/H+ exchanger inhibitor, KR‐33028 was evaluated in rats after intravenous and oral administration. After intravenous administration of KR‐33028 (1, 5, 10 and 20mg/kg doses), the systemic clearance (Cl) was reduced and AUC was nonlinearly increased as a function of dose. The volume of distribution (Vss), however, remained unchanged as the dose was increased, which was consistent with unaltered plasma protein binding in vitro (unbound fraction = 0.09–0.12). Upon oral administration (2, 10 and 20mg/kg doses), KR‐33028 was rapidly absorbed, and this was consistent with high Caco‐2 Papp values found in vitro. There were nonlinear increases in AUC and Cmax, and the absolute oral bioavailability (F) was significantly increased as the dose was increased (F = 23.3%, 40.7% and 78.2% for 2, 10 and 20mg/kg doses, respectively). The extent of urinary excretion was low for both intravenous (0.5–0.7%) and oral (0.2–0.8%) doses. The reduced systemic clearance and increased oral bioavailability at high doses appears to be due to a saturable first‐pass metabolism. Copyright © 2007 John Wiley & Sons, Ltd.
Physically based animation of sandstorm
Authors: Liu Shiguang , Wang Zhangye , Gong Zheng , Huang Lei , Peng Qunsheng 
Published: September 2007

AbstractThis paper describes a physically based method for modeling and animating sandstorm, a type of disastrous natural phenomenon. The method adopts a relatively stable incompressible multiple fluid model to simulate the motion of air, sand, and dust particles. The wind field of sandstorm is established based on Reynold‐average Navier‐Stokes equations. The sand and dust particle flow is therefore computed taking interaction among the wind, sand, and dust particles into account. To accelerate the modeling process of a dynamic sandstorm scene, a special Multi‐Fluid Solver is designed and implemented on GPU. Various illumination effects of sandstorm scenes can be simulated by spectral sampling scattering calculation. Animations of realistic sandstorms occurring in desert and urban areas based on our model are demonstrated. Compared with the real sandstorm photos, our simulated results are satisfactory. Copyright © 2007 John Wiley & Sons, Ltd.
Asymmetric Organocatalytic Biginelli Reactions: A New Approach To Quickly Access Optically Active 3,4‐Dihydropyrimidin‐2‐(1H)‐ones
Authors: Gong Liu‐Zhu , Chen Xiao‐Hua , Xu Xiao‐Ying 
Published: September 2007

AbstractThe Biginelli reaction, known for over 100 years, is an important multicomponent reaction for accessing dihydropyrimidinones (DHPMs). The individual enantiomers of DHPMs exhibit different or even opposite pharmaceutical activities, which require synthetic methods to easily access the optically pure DHPMs. In recent decades, many efforts have focused on developing procedures for the preparation of optically active Biginelli products. In this article, we will summarize the developments in the synthetic methods to access optically active DHPMs with an emphasis on the recent advances in the asymmetric catalytic Biginelli reactions, along with concepts to design the organocatalytic asymmetric variants.
EMR1, the human homolog of F4/80, is an eosinophil‐specific receptor
Authors: Hamann Jörg , Koning Nathalie , Pouwels Walter , Ulfman Laurien H. , van Eijk Marco , Stacey Martin , Lin Hsi‐Hsien , Gordon Siamon , Kwakkenbos Mark J. 
Published: September 2007

AbstractThe EGF‐TM7 F4/80 is a defining marker of murine macrophage populations. Applying flow cytometric analysis using the newly generated mAb A10, and quantitative real‐time PCR, we here report the surprising observation that the human ortholog of F4/80, EGF‐like module containing mucin‐like hormone receptor (EMR)1, is absent on mononuclear phagocytic cells including monocytes, macrophages, and myeloid dendritic cells. Unexpectedly, we found that EMR1 expression is restricted to eosinophilic granulocytes, where expression is overlapping with the eotaxin receptor CCR3 and the immunoglobulin‐like lectin Siglec‐8. Absence on other leukocytes, including basophils, implies that EMR1 is a highly specific marker for eosinophils in humans.
On the crossing numbers of Cartesian products with trees
Authors: Bokal Drago 
Published: September 2007

AbstractZip product was recently used in a note establishing the crossing number of the Cartesian product K1,n □ Pm. In this article, we further investigate the relations of this graph operation with the crossing numbers of graphs. First, we use a refining of the embedding method bound for crossing numbers to weaken the connectivity condition under which the crossing number is additive for the zip product. Next, we deduce a general theorem for bounding the crossing numbers of (capped) Cartesian product of graphs with trees, which yields exact results under certain symmetry conditions. We apply this theorem to obtain exact and approximate results on crossing numbers of Cartesian product of various graphs with trees. © 2007 Wiley Periodicals, Inc. J Graph Theory 56: 287–300, 2007
Vom Kombinat zum Konzern
Authors: Knörck Constanze 
Published: September 2007

AbstractAnfang der Neunziger Jahre sollte sie noch das Zeiss‐Kombinat in Jena abwickeln. Heute ist Jenoptik ein kerngesundes Unternehmen, das sich nicht mehr um die Bestandssicherung sorgen muss. Seit dem 1. Juli wird das Unternehmen von Dr. Michael Mertin geführt. Andreas Thoß sprach im Interview mit ihm über die neue Jenoptik, Ziele und Strategien.