bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics of the analogs at C3 and C5 ofm‐nifedipine in beagle dogs
Authors: Yang Zhi‐fu , Zhou Si‐yuan , Yang Tie‐hong , Liu Xin‐you , Mei Qi‐bing 
Published: December 2008

AbstractThe prototype 1,4‐dihydropyridine (1,4‐DHP) nifedipine, indicated for the management of hypertension and angina pectoris, has disadvantages including photodegradation and a short half‐life. Several newer 1,4‐DHPs, includingm‐nifedipine and its analogs at the C3, C5 position such as MN9201, MN9202 and MN9203, have been designed to offset these problems. The aim of this study was to investigate the pharmacokinetic characteristics of these derivatives to provide reference for their further evaluation and modification. Derivatives were intravenously bolus administered to beagle dogs. The drug concentration in the plasma was determined by the HPLC method. The pharmacokinetic parameters were calculated by the non‐compartmental method. The analysis of variance (ANOVA) was used to compare the pharmacokinetic parameters of the derivatives. The results showed that the area under the curve from time zero to the last sampling time (AUC0‐t) ofm‐nifedipine, MN9201, MN9202 and MN9203 was 45.1 ± 13.6, 51.7 ± 15.2, 70 ± 16 and 62 ± 12.4 µmol/l*min, respectively. The elimination half‐life (t1/2) was 98 ± 24, 129 ± 55, 190 ± 21 and 92 ± 25min, respectively. Thet1/2of MN9202 was significantly longer than those of the others (p<0.05 orp<0.01). These results suggest that the length of the carbon chain at the C3 or C5 position in the derivatives had a marked effect on its metabolism, and M9202 is a promising new drug candidate worth further evaluation. Copyright © 2008 John Wiley & Sons, Ltd.
Plasma zinc concentrations of mothers and the risk of oral clefts in their children in Utah
Authors: Munger Ronald G. , Tamura Tsunenobu , Johnston Kelley E. , Feldkamp Marcia L. , Pfister Roxane , Carey John C. 
Published: December 2008

AbstractBACKGROUND: The role of maternal zinc nutrition in human oral clefts (OCs) is unclear. We measured plasma zinc concentrations (PZn) of case and control mothers to evaluate the associations between PZn and risk of OCs with and without other malformations. METHODS: Case mothers were ascertained by the Utah Birth Defects Network and control mothers were selected from Utah birth certificates by matching for child gender and delivery month and year. Maternal blood was collected >1 year after the last pregnancy. PZn was available for 410 case mothers who were divided into four subgroups: isolated cleft lip with or without cleft palate (CL/P‐I, n = 231), isolated cleft palate (CP‐I, n = 74), CL/P with other malformations (CLP‐M, n = 42), and CP with other malformations (CP‐M, n = 63). PZn was available for 447 control mothers. The mean age of children at blood sampling was 3.7 years for all cases combined and 4.3 years for controls. RESULTS: Mean PZns of all groups were similar, and low PZn (<11.0 μmol/L) was found in 59% of cases and 62% of controls. Risk of OCs did not vary significantly across PZn quartiles for the four subgroups individually and all OC groups combined. CONCLUSIONS: We previously reported that poor maternal zinc status was a risk factor for OCs in the Philippines, where OC prevalence is high and maternal PZn is low. In Utah, however, no such association was found, suggesting that poor maternal zinc status may become a risk factor only when zinc status is highly compromised. Birth Defects Research (Part A), 2009. © 2008 Wiley‐Liss, Inc.
Maternal vasoactive exposures, amniotic bands, and terminal transverse limb defects
Authors: Werler Martha M. , Bosco Jaclyn L. F. , Shapira Stuart K. 
Published: December 2008

AbstractBACKGROUND:Limb reduction deficiencies that are accompanied by amniotic bands (AB‐Ls) and terminal transverse limb deficiencies (TLDs) have each been attributed to vascular disruption; for the former, however, it is not clear if amniotic bands are the primary cause of or are secondary to vascular disruption. If amniotic bands are secondary to vascular disruption, then a shared pathogenesis for each case group might be exhibited by similar risk factors.METHODS:We evaluated maternal age, education, race/ethnicity, parity, pregnancy wantedness, and vasoactive exposures among 139 AB‐L and 373 TLD cases, using interview data collected from mothers in 10 states by the National Birth Defects Prevention Study. Vasoactive exposures included maternal cigarette smoking and use of decongestants, nonsteroid anti‐inflammatory drugs, and antihypertensive drugs in the periconceptional period.RESULTS:Increased risk estimates were observed for Black mothers (OR 2.5; 95% CI: 1.5–4.1) and nulliparous mothers (2.1; 1.4–3.0) in relation to AB‐L, while neither was associated with TLD. Hispanic women (1.4; 1.0–1.9) and those not wanting the pregnancy (1.5; 1.1–2.1) had increased risks of TLD, but not AB‐L. Maternal cigarette smoking and aspirin use each increased the risk of AB‐L, but not TLD; while decongestants and possibly antihypertensive medications increased the risk of TLD, but not AB‐L.CONCLUSIONS:The lack of consistent findings for the two case groups suggests that AB‐L and TLD may be distinct entities. The inconsistencies also suggest that these vasoactive exposures may not be markers for vascular disruption or that vascular disruption may not play a major role in the pathogenesis of these two types of limb deficiencies. Birth Defects Research (Part A), 2009. © 2008 Wiley‐Liss, Inc.
Early‐life environment, developmental immunotoxicology, and the risk of pediatric allergic disease including asthma
Authors: Dietert Rodney R. , Zelikoff Judith T. 
Published: December 2008

AbstractIncidence of childhood allergic disease including asthma (AD‐A) has risen since the mid‐20th century with much of the increase linked to changes in environment affecting the immune system. Childhood allergy is an early life disease where predisposing environmental exposures, sensitization, and onset of symptoms all occur before adulthood. Predisposition toward allergic disease (AD) is among the constellation of adverse outcomes following developmental immunotoxicity (DIT; problematic exposure of the developing immune system to xenobiotics and physical environmental factors). Because novel immune maturation events occur in early life, and the pregnancy state itself imposes certain restrictions on immune functional development, the period from mid‐gestation until 2 years after birth is one of particular concern relative to DIT and AD‐A. Several prenatal‐perinatal risk factors have been identified as contributing to a DIT‐mediated immune dysfunction and increased risk of AD. These include maternal smoking, environmental tobacco smoke, diesel exhaust and traffic‐related particles, heavy metals, antibiotics, environmental estrogens and other endocrine disruptors, and alcohol. Diet and microbial exposure also significantly influence immune maturation and risk of allergy. This review considers (1) the critical developmental windows of vulnerability for the immune system that appear to be targets for risk of AD, (2) a model in which the immune system of the DIT‐affected infant exhibits immune dysfunction skewed toward AD, and (3) the lack of allergy‐relevant safety testing of drugs and chemicals that could identify DIT hazards and minimize problematic exposure of pregnant women and children. Birth Defects Res (Part B) 2008. © 2008 Wiley‐Liss, Inc.
Phosphate: Known and potential roles during development and regeneration of teeth and supporting structures
Authors: Foster Brian L. , Tompkins Kevin A. , Rutherford R. Bruce , Zhang Hai , Chu Emily Y. , Fong Hanson , Somerman Martha J. 
Published: December 2008

AbstractInorganic phosphate (Pi) is abundant in cells and tissues as an important component of nucleic acids and phospholipids, a source of high‐energy bonds in nucleoside triphosphates, a substrate for kinases and phosphatases, and a regulator of intracellular signaling. The majority of the body's Pi exists in the mineralized matrix of bones and teeth. Systemic Pi metabolism is regulated by a cast of hormones, phosphatonins, and other factors via the bone‐kidney‐intestine axis. Mineralization in bones and teeth is in turn affected by homeostasis of Pi and inorganic pyrophosphate (PPi), with further regulation of the Pi/PPi ratio by cellular enzymes and transporters. Much has been learned by analyzing the molecular basis for changes in mineralized tissue development in mutant and knock‐out mice with altered Pi metabolism. This review focuses on factors regulating systemic and local Pi homeostasis and their known and putative effects on the hard tissues of the oral cavity. By understanding the role of Pi metabolism in the development and maintenance of the oral mineralized tissues, it will be possible to develop improved regenerative approaches. Birth Defects Research (Part C) 84:281–314, 2008. © 2008 Wiley‐Liss, Inc.
Mammalian regeneration and regenerative medicine
Authors: Muneoka Ken , Allan Christopher H. , Yang Xiaodong , Lee Jangwoo , Han Manjong 
Published: December 2008

AbstractMammals are generally considered to be poor regenerators, yet there are a handful of mammalian models that display a robust ability to regenerate. One such system is the regenerating tips of digits in both humans and mice. In vitro studies of regenerating fetal human and mouse digit tips display both anatomical and molecular similarities, indicating that the mouse digit is a clinically relevant model. At the same time, genetic studies on mouse digit tip regeneration have identified signaling pathways required for the regeneration response that parallel those known to be important for regeneration in lower vertebrates. In addition, recent studies establish that digit tip regeneration involves the formation of a blastema that shares similarities with the amphibian blastema, thus establishing a conceptual bridge between clinical application and basic research in regeneration. In this review we discuss how the study of endogenous regenerating mammalian systems is enhancing our understanding of regenerative mechanisms and helping to shed light on the development of therapeutic strategies in regenerative medicine. Birth Defects Research (Part C) 84:265–280, 2008. © 2008 Wiley‐Liss, Inc.
Pathogenic Mutations Shift the Equilibria of α‐Synuclein Single Molecules towards Structured Conformers
Authors: Brucale Marco , Sandal Massimo , Di Maio Selena , Rampioni Aldo , Tessari Isabella , Tosatto Laura , Bisaglia Marco , Bubacco Luigi , Samorì Bruno 
Published: December 2008

Abstractα‐synuclein (α‐Syn) is an abundant brain protein whose mutations have been linked to early‐onset Parkinson's disease (PD). We recently demonstrated, by means of a single‐molecule force spectroscopy (SMFS) methodology, that the conformational equilibrium of monomeric wild‐type (WT) α‐Syn shifts toward β‐containing structures in several unrelated conditions linked to PD pathogenicity. Herein, we follow the same methodology previously employed for WT α‐Syn to characterize the conformational heterogeneity of pathological α‐Syn mutants A30P, A53T, and E46K. Contrary to the bulk ensemble‐averaged spectroscopies so far employed to this end by different authors, our single‐molecule methodology monitored marked differences in the conformational behaviors of the mutants with respect to the WT sequence. We found that all the mutants have a much higher propensity than the WT to adopt a monomeric compact conformation that is compatible with the acquiring of β structure. Mutants A30P and A53T show a similar conformational equilibrium that is significantly different from that of E46K. Another class of conformations, stabilized by mechanically weak interactions (MWI), shows a higher variety in the mutants than in the WT protein. In the A30P mutant these interactions are relatively stronger, and therefore the corresponding conformations are possibly more structured. The more structured and globular conformations of the mutants can explain their higher propensity to aggregate with respect to the WT.
Pulmonary arterial hypertension and right heart failure—A late‐onset complication after cardiac catheterization
Authors: Koch Beate , Ewert Ralf , Puls Ralf , Gläser Sven 
Published: December 2008

AbstractArteriovenous fistula is a possible complication of diagnostic procedures requiring arterial femoral catheterization. Late onset manifestation is reported rarely. An impressive case of severe pulmonary arterial hypertension and consecutive right heart failure caused by an arteriovenous fistula between the common iliac artery and the distal inferior caval vein manifesting four years after cardiac catheterization in described. © 2009 Wiley‐Liss, Inc.
Percutaneous closure of patent foramen ovale for migraine headaches refractory to medical treatment
Authors: Wahl Andreas , Praz Fabien , Findling Oliver , Nedeltchev Krassen , Schwerzmann Markus , Tai Tony , Windecker Stephan , Mattle Heinrich P. , Meier Bernhard 
Published: December 2008

AbstractBackground: Patent foramen ovale (PFO) has been linked to migraine, and several retrospective studies reported an improvement in migraine prevalence or frequency after PFO closure for other reasons, mostly for secondary prevention of paradoxical embolism or following diving accidents. We investigated the outcome of patients undergoing PFO closure solely for migraine headaches refractory to medical treatment. Methods: Seventeen patients (age 44 ± 12 years; 76% female; one atrial septal aneurysm) underwent percutaneous PFO closure using the Amplatzer PFO Occluder (AGA Medical Corporation, Golden Valley, MN). An 18‐mm device was used in two patients, a 25‐mm device in 13, and a 35‐mm device in two. The interventions were solely guided by fluoroscopy, without intraprocedural echocardiography. Results: All implantation procedures were successful. There were no peri‐procedural complications. Contrast transesophageal echocardiography after Valsalva maneuver at 6 months showed complete PFO closure in 16 patients (94%), whereas a minimal residual shunt persisted in one (6%). During 2.7 ± 1.5 years of follow‐up, no deaths and no embolic events occurred. After PFO closure, migraine headaches disappeared in four patients (24%), and improved in eight additional patients (47%). Three patients (18%) reported a decrease of their headaches by 75%, three patients (18%) a decrease of 50%, and two patients (12%) a decrease of 25%, while headaches remained unchanged in five patients (29%). No patient experienced worsening headaches. Moreover, the prevalence of migraine with aura decreased from 82 to 24% (P = 0.002). Conclusions: These results suggest that percutaneous PFO closure durably alters the spontaneous course of shunt associated migraine. © 2009 Wiley‐Liss, Inc.
Multivessel drug‐eluting stenting and impact of diabetes mellitus—A report from the EVENT registry
Authors: Novack Victor , Tsyvine Daniel , Cohen David J. , Pencina Michael , Dubin Joseph , Dehghani Hossein , Kleiman Neal S. , Cutlip Donald E. 
Published: December 2008

AbstractObjectives: To compare clinical outcomes in patients with and without diabetes after multivessel percutaneous coronary intervention (PCI). Background: Diabetes is associated with significantly worse outcomes after multivessel PCI and coronary bypass surgery is recommended as the preferred option for these patients. Methods and Results: The Evaluation of Drug Eluting Stents and Ischemic Events registry is a multicenter evaluation of acute and 1 year outcomes in unselected patients undergoing PCI since approval of drug‐eluting stents (DES). Major adverse cardiac events (MACE) were defined as all cause mortality, myocardial infarction, or repeat revascularization and rate was estimated by Kaplan‐Meier method and compared using log‐rank. The independent correlates of MACE were determined using Cox proportional hazards regression. Of 4,819 nonemergency native coronary DES procedures, 1,595 (33.1%) were in patients with diabetes and 722 (11.7%) involved >1 vessel. Of patients undergoing multivessel procedures, diabetes was present in 256 (35.5%). One year after multivessel PCI, MACE was similar for patients with or without diabetes (22.3% versus 21.2%, log‐rank test P = 0.85). The independent correlates of 1 year MACE were female sex (Hazard ratio [HR], 1.58, 95% CI 1.14–2.20), ejection fraction (HR 0.74 per group [<25%, 26–35%, 36–50%, and >50%], 95%CI 0.59–0.94) and number of stents (HR 1.20 per stent, 95%CI 1.04–1.38) but not diabetes (HR 1.00, 95% CI 0.71–1.39). Conclusions: Multivessel DES is performed commonly in patients with diabetes with outcomes at 1 year similar to patients without diabetes. Longer follow‐up is required to more fully evaluate the safety and effectiveness of this strategy. © 2009 Wiley‐Liss, Inc.
Percutaneous closure of a periprosthetic leakage after mitral valve reoperation due to recurrent endocarditis
Authors: Kuehl Matthias , Schreieck Juergen , Burgstahler Christof 
Published: December 2008

AbstractParavalvular leakage following the atrioventricular valve replacement, though mostly harmless with insignificant morbidity, can result in heart failure and significant hemolysis that requires treatment. Reoperation is still the treatment of choice, but there is a high risk of recurrence, especially in patients with a history of endocarditis and/or those who have already undergone reoperation for paravalvular leakage. Recently, percutaneous closure of perivalvular leaks with occluders or coils have become an alternative to surgery. However, up to now, the collective of patients who benefit from this approach still has to be defined. Here, we present a case of a highly symptomatic 64‐year‐old male with severe hemolysis caused by paravalvular leakages after reoperation of a mechanical mitral valve replacement due to recurrent endocarditis. © 2009 Wiley‐Liss, Inc.
Highly Enantioselective Synthesis of Linear β‐Amino Alcohols
Authors: Métro Thomas‐Xavier , Gomez Pardo Domingo , Cossy Janine 
Published: December 2008

Abstractβ‐Amino alcohols derived from α‐amino acids have been extensively used as a powerful source of chirality. Transforming the alcohol moiety into a good leaving group has allowed the rearrangement of these β‐amino alcohols and the introduction of a large number of nucleophiles through the anchimeric participation of the nitrogen atom. An overview on the recent progress realized on the rearrangement of these β‐amino alcohols in the presence of (CF3CO)2O and H2SO4 is reported.
Enantioselective Synthesis of Functionalized Nitrocyclopropanes by Organocatalytic Conjugate Addition of Bromonitroalkanes to α,β‐Unsaturated Enones
Authors: Lv Jian , Zhang Jiaming , Lin Zhu , Wang Yongmei 
Published: December 2008

AbstractA general enantioselective synthesis of functionalized nitrocyclopropanes by organocatalytic conjugate addition of a variety of bromonitroalkanes to α,β‐unsaturated enone systems is presented. The process, efficiently catalyzed by the salts of 9‐amino‐9‐deoxyepiquinine 1 d serves as a powerful approach to the preparation of synthetically and biologically important cyclopropanes with high levels of enantio‐ and diastereoselectivities. Since only 0.6 equivalents of bromonitromethane are used as a reagent, (S)‐2 e is obtained enantiomerically pure by employing chiral 1 d as a highly efficient catalyst for its kinetic resolution (97 % ee at 51 % conversion, selectivity s=120).
Synthesis of Structurally Well‐Defined Telechelic Polymers by Organostibine‐Mediated Living Radical Polymerization: In Situ Generation of Functionalized Chain‐Transfer Agents and Selective ω‐End‐Group Transformations
Authors: Yamago Shigeru , Yamada Takeshi , Togai Manabu , Ukai Yuu , Kayahara Eiichi , Pan Na 
Published: December 2008

AbstractSeveral organostibine chain‐transfer agents possessing polar functional groups have been prepared by the reactions of azo initiators and tetramethyldistibine (1). Carbon‐centered radicals thermally generated from the azo initiators were trapped by 1 to yield the corresponding organostibine chain‐transfer agents. The high yields observed in the synthesis of the chain‐transfer agents strongly suggest that distibines have excellent radicophilic reactivity. As the reactions proceeded under neutral conditions, functional groups that are incompatible with ionic conditions were incorporated into the chain‐transfer agents. The chain‐transfer agents were used in living radical polymerization to synthesize the corresponding α‐functionalized polymers. As the functional groups in the chain‐transfer agents did not interfere with the polymerization reaction, well‐controlled polymers possessing number‐average molecular weights (Mns) predetermined by the monomer/transfer agent ratios were synthesized with low polydispersity indices (PDIs). The organostibanyl ω‐polymer ends were transformed into a number of different functional groups by radical‐coupling, radical‐addition, and oxidation reactions. Therefore, it was possible to synthesize well‐controlled telechelic polymers with the same and also with different functional groups at their α‐ and ω‐polymer ends. Distibine 1 was also found to increase PDI control in the living radical polymerization of styrene and methyl methacrylate (MMA) using a purified organostibine chain‐transfer agent. Well‐controlled poly(methyl methacrylate)s with Mn values ranging from 10 000 to 120 000 with low PDIs (1.05–1.15) were synthesized by the addition of a catalytic amount of 1. The results have been attributed to the high reactivity of distibine 1 towards polymer‐end radicals, which are spontaneously deactivated to yield organostibine dormant species.
Breaking the Mirror: pH‐Controlled Chirality Generation from a meso Ligand to a Racemic Ligand
Authors: Zhang Lei , Zhang Jian , Li Zhao‐Ji , Qin Ye‐Yan , Lin Qi‐Pu , Yao Yuan‐Gen 
Published: December 2008

AbstractTo study the conversion from a meso form to a racemic form of tetrahydrofurantetracarboxylic acid (H4L), seven novel coordination polymers were synthesized by the hydrothermal reaction of Zn(NO3)2⋅6 H2O with (2S,3S,4R,5R)‐H4L in the presence of 1,10‐phenanthroline (phen), 2,2′‐bipyridine (2,2′‐bpy), or 4,4′‐bipyridine (4,4′‐bpy): [Zn2{(2S,3S,4R,5R)‐L}(phen)2(H2O)]⋅2 H2O (1), [Zn4{(2S,3R,4R,5R)‐L}{(2S,3S,4S,5R)‐L}(phen)2(H2O)2] (2), [Zn2{(2S,3S,4R,5R)‐L}(H2O)2]⋅H2O (3), [Zn4{(2S,3R,4R,5R)‐L}{(2S,3S,4S,5R)‐L} (2,2′‐bpy)2(H2O)2]⋅2 H2O (4), [Zn2 {(2S,3S,4R,5R)‐L}(2,2′‐bpy)(H2O)] (5), [Zn4{(2S,3R,4R,5R)‐L}{(2S,3S,4S,5R)‐L} (4,4′‐bpy)2(H2O)2] (6), and [Zn2 {(2S,3S,4R,5R)‐L}(4,4′‐bpy)(H2O)]⋅ 2 H2O (7). These complexes were obtained by control of the pH values of reaction mixtures, with an initial of pH 2.0 for 1, 2.5 for 2, 4, and 6, and 4.5 for 3, 5, and 7, respectively. The expected configuration conversion has been successfully realized during the formation of 2, 4, and 6, and the enantiomers of L, (2S,3R,4R,5R)‐L and (2S,3S,4S,5R)‐L, are trapped in them, whereas L ligands in the other four complexes retain the original meso form, which indicates that such a conversion is possibly pH controlled. Acid‐catalyzed enol–keto tautomerism has been introduced to explain the mechanism of this conversion. Complex 1 features a simple 1D metal–L chain that is extended into a 3D supramolecular structure by π–π packing interactions between phen ligands and hydrogen bonds. Complex 2 has 2D racemic layers that consist of centrosymmetric bimetallic units, and a final 3D supramolecular framework is formed by the interlinking of these layers through π–π packing interactions of phen. Complex 3 is a 3D metal–organic framework (MOF) involving meso‐L ligands, which can be regarded as (4,6)‐connected nets with vertex symbol (45.6)(47.68). Complexes 4 and 5 contain 2D racemic layers and (6,3)‐honeycomb layers, respectively, both of which are combined into 3D supramolecular structures through π–π packing interactions of 2,2′‐bpy. The structure of complex 6 is a 2D network formed by 4,4′‐bpy bridging 1D tubes, which consist of metal atoms and enantiomers of L. These layers are connected through hydrogen bonds to give the final 3D porous supramolecular framework of 6. Complex 7 is a 3D MOF with novel (3,4,5)‐connected (63)(42.64)(42.66.82) topology. The thermal stability of these compounds was also investigated.