bluuebunny/crossref_metadata_2025 huggingface dataset:
Delayed neural network degeneration after neonatal hypoxia‐ischemia
Authors: Stone Brian S. , Zhang Jiangyang , Mack Devin W. , Mori Susumu , Martin Lee J. , Northington Frances J.
Published: December 2008

Objective

Clinical magnetic resonance studies show delayed and ongoing neurodegeneration after neonatal hypoxia‐ischemia (HI), but the mechanisms and timing of this neurodegeneration remain unclear. We used ex vivo diffusion tensor imaging (DTI) and brain neuropathology to determine whether selective injury to white matter tracts occurs after neonatal HI in mice resulting in neural system–associated attrition in remote regions and at delayed times.

Methods

The Rice–Vannucci model (unilateral carotid ligation + 45 minutes of hypoxia FiO2 = 0.08) was used to cause brain injury in postnatal day 7 (p7) C57BL6 mice, and ex vivo DTI and correlative neuropathology were performed at p8, p11, p15, p21, p28, and p42.

Results

DTI provides excellent contrast visualization of unmyelinated white matter in the immature mouse brain. Severe ipsilateral injury to the hippocampus is seen with both histopathology and diffusion‐weighted magnetic resonance imaging 24 hours after injury. Injury to axons is evident 24 hours after HI in the hippocampal alveus. By p11 and continuing until p28, the ipsilateral fimbria fornix degenerates. At p15, there is injury and loss of axons entering the ipsilateral septal nucleus followed by ipsilateral septal atrophy. Volume loss in the hippocampus is rapid and severe, but is subacute and significantly slower in the ipsilateral septum. Neonatal HI also interrupts the normal developmental increase in fractional anisotropy in the ipsilateral fimbria but not in the contralateral fimbria from p8 to p42.

Interpretation

In neonatal brain, there is progressive systems‐preferential injury after HI. DTI allows unparalleled visualization of this neural network–associated attrition so that it can be followed longitudinally in developing brain. Ann Neurol 2008;64:535–546
Umbilical cord blood transplantation for juvenile metachromatic leukodystrophy
Authors: Pierson Tyler Mark , Bonnemann Carsten G. , Finkel Richard S. , Bunin Nancy , Tennekoon Gihan I.
Published: December 2008

Three siblings with metachromatic leukodystrophy underwent umbilical cord blood transplantation at different stages of disease. Neuroimaging, nerve conduction studies, neurological examinations, and neuropsychological examinations were used to measure outcome over 2 years. After transplant, the oldest sibling experienced disease progression. His two siblings had near or total resolution of signal abnormalities on neuroimaging. Their neuropsychological testing remained stable, and nerve conduction studies have shown improvement. These results indicate pretransplantation neurological examinations may be the most significant predictor of outcome after transplant. To our knowledge, this report is the first to document neurological outcome of metachromatic leukodystrophy treated by umbilical cord blood transplantation. Ann Neurol 2008;64:583–587
Die C‐C‐Kreuzkupplung nach Liebeskind und Srogl
Authors: Prokopcová Hana , Kappe C. Oliver
Published: December 2008

Über Schwefel zum Erfolg: Die Kreuzkupplung von organischen Schwefelverbindungen mit Boronsäuren unter neutralen Bedingungen in Gegenwart eines Palladium(0)‐Katalysators und einer stöchiometrischen Menge eines Kupfer(I)‐Cofaktors hat sich als wertvolle C‐C‐Verknüpfungsmethode etabliert (siehe Schema). Diese basenfreie Kupplung verläuft nach einem beispiellosen Mechanismus und hat deutliche Vorteile, wenn andere Pd0‐katalysierte Verfahren versagen.

magnified image

Um die Fülle an bereits bekannten hoch selektiven und zuverlässigen Methoden zur C‐C‐Bindungsknüpfung zu ergänzen, besteht ein wachsendes Interesse an der Entwicklung neuer Verfahren mit einer veränderten oder orthogonalen Reaktivität. Liebeskind und Srogl beschrieben 2000 eine übergangsmetallkatalysierte Kreuzkupplung von Thioestern mit Boronsäuren zur Synthese von Ketonen unter neutralen Bedingungen. Diese desulfurierende Kreuzkupplung verläuft unter Palladium(0)‐Katalyse mit stöchiometrischem Kupfer(I)‐Zusatz, folgt einem beispiellosen Mechanismus und ist auf eine Reihe von Organoschwefelderivaten und nucleophilen Organometallreagentien anwendbar. Hier betrachten wir neuere Anwendungen dieser faszinierenden Reaktion in der organischen Synthese. Besondere Berücksichtigung finden Fälle, bei denen herkömmliche Methoden der C‐C‐Bindungsbildung versagt haben.
Synthesis, structure, and phase behavior of new chiral liquid‐crystalline polysiloxanes based on mesogenic menthyl monomers
Authors: Zhang Bao‐Yan , Hu Jian‐She , Ren Shi‐Chao , Liu Cong
Published: December 2008

Six new chiral monomers (M1–M6), and their corresponding side chain polymers (P1–P6) containing menthyl groups were synthesized. The chemical structures of M1–M6 were characterized with FTIR and 1H NMR. The structure–property relationships of the monomers and polymers obtained are discussed. The mesomorphic properties and phase behavior were investigated by differential scanning calorimetry, thermogravimetric analysis, polarizing optical microscopy, and X‐ray diffraction measurements. Some compounds containing menthyl groups formed mesophase when a flexible spacer was inserted between the mesogenic core and the menthyl groups by reducing the steric hindered effect. The monomers M1, M4, and M5 did not reveal mesomorphic properties because of the weaker rigid core or the longer flexible terminal groups, whereas M2, M3, and M6 all revealed cholesteric phase. Except P4 and P5, the homopolymers P1–P3 and P6 showed a smectic A phase. In addition, melting, glass transition temperature, or clearing temperature increased, and the mesophase temperature range widened with increasing the rigidity of mesogenic core or decreasing the length of the flexible spacer. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Environmental impact of razor clam harvesting using salt in Ria Formosa lagoon (Southern Portugal) and subsequent recovery of associated benthic communities
Authors: Constantino Rita , Gaspar Miguel B. , Pereira Fábio , Carvalho Susana , Cúrdia João , Matias Domitília , Monteiro Carlos C.
Published: December 2008

Razor clams are found in different habitats ranging from sheltered systems (e.g. lagoons and estuaries) to open coasts. They are distributed worldwide and comprise a small number of species of high economic value. Depending on the specific habitat and species exploited, different mechanical and hand‐harvesting techniques are employed. While the environmental effects resulting from mechanized methods have been described by several authors, the impacts caused by traditional hand‐harvesting methods remain unknown. Therefore, a study was undertaken in Ria Formosa lagoon (South of Portugal) addressing the environmental effects resulting from harvestingSolen marginatuswith salt.

No significant impact on the sediment was found; the main effect was an increase in salinity after covering the area with salt, which decreased rapidly with the flood tide and after a few hours had returned to pre‐harvesting levels.

No effects on benthic communities were observed, with similar fluctuation patterns recorded in control and experimental areas, the observed differences being attributed to the natural variability of benthic populations.

Based on the results obtained in the present study, a razor clam fishery using salt in intertidal areas can be considered environmentally ‘friendly’.

Copyright © 2008 John Wiley & Sons, Ltd.
Structures, dynamics and stability of reef fish assemblages in non‐reefal coral communities in Hong Kong, China
Authors: Tam Tze‐Wai , Ang Put O.
Published: December 2008

A detailed study on the spatial and temporal patterns of reef fish assemblages associated with non‐reefal coral communities at A Ma Wan (AMW) and A Ye Wan (AYW) in Tung Ping Chau, Hong Kong, China, was carried out using an underwater visual census method from January 1998 to December 1999.

The study identified a total of 106 species (76 genera in 39 families) of fish in the study sites, in which 88 species were recorded in AMW and 78 species in AYW. Seasonal patterns in the abundance and species richness of all reef fishes and most of the frequently encountered families/trophic groups in both study sites were observed. Seasonal fluctuation of macroalgae, the influence of recruitment of larvae, and the possible seasonal variation in the behaviour of fish may all contribute to these observed seasonal patterns.

Multidimensional scaling (MDS) ordinations demonstrated that there were spatial variations in the fish community structures within and between sites. Such spatial patterns were possibly related to the spatial variation of the coral community structures in the study sites. The ordinations also showed that the fish community structures in the study sites were not seasonally stable. Such temporal instability of the fish community structures may be partly due to habitat isolation among the fish communities around the island.

These results imply that preservation and enhancement of habitat connectivity of the coral communities should be one of the main conservation strategies for the reef fish communities of Tung Ping Chau, and those of Hong Kong in general. This strategy may be equally applicable to other non‐reefal coral communities elsewhere around the world.

Copyright © 2008 John Wiley & Sons, Ltd.
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

The 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

BACKGROUND: 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

BACKGROUND: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

Incidence 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

Inorganic 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

Mammals 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

α‐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

Arteriovenous 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

Background: 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

Objectives: 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

Paravalvular 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

β‐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

A 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

Several 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

To 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.
How to Extend the Use of Grid‐Based Interaction Energy Maps from Chemistry to Biotopics
Authors: Caron Giulia , Nurisso Alessandra , Ermondi Giuseppe
Published: December 2008

Many computational tools routinely used in chemistry could successfully be applied to the biosciences since protein–protein and protein–ligand interactions are governed by the laws of chemistry. This paper shows that it is possible to extend the use of existing computational tools from their traditional application field (e.g.chemistry) to culturally‐related research areas by the implementation of simple but well‐designed utilities. In particular, a computational strategy obtained by combining GRID (the program originally designed by Peter Goodford, and now distributed by Molecular Discovery Ltd.) and BIOCUBE4mf (an application freely available atwww.casmedchem.unito.it) was used to a) characterize the surface properties of the cavity of theBacillus anthracisprotective antigen heptameric prepore; b) suggest how to design mutagenesis experiments; c) quantitatively show the selectivity of the KvAP channel for K+over Na+ions and d) rationalize the pharmacokinetic behavior of 1,4‐DHP third‐generation drugs.
Virtual Screening and Biological Characterization of Novel Histone Arginine Methyltransferase PRMT1 Inhibitors
Authors: Heinke Ralf , Spannhoff Astrid , Meier Rene , Trojer Patrick , Bauer Ingo , Jung Manfred , Sippl Wolfgang
Published: December 2008

Lysine and arginine methyltransferases participate in the posttranslational modification of histones and regulate key cellular functions. Protein arginine methyltransferase 1 (PRMT1) has been identified as an essential component of mixed lineage leukemia (MLL) oncogenic complexes, revealing its potential as a novel therapeutic target in human cancer. The first potent arginine methyltransferase inhibitors were recently discovered by random‐ and target‐based screening approaches. Herein we report virtual and biological screening for novel inhibitors of PRMT1. Structure‐based virtual screening (VS) of the Chembridge database composed of 328 000 molecules was performed with a combination of ligand‐ and target‐based in silico approaches. Nine inhibitors were identified from the top‐scored docking solutions; these were experimentally tested using human PRMT1 and an antibody‐based assay with a time‐resolved fluorescence readout. Among several aromatic amines, an aliphatic amine and an amide were also found to be active in the micromolar range.
Indoor tanning use among adolescents in the US, 1998 to 2004
Authors: Cokkinides Vilma , Weinstock Martin , Lazovich DeAnn , Ward Elizabeth , Thun Michael
Published: December 2008

BACKGROUND:

A recent meta‐analysis found that indoor tanning use before the age of 35 years increases the risk of melanoma, supporting policies to restrict indoor tanning use among adolescents. The objectives of the current study were to provide a national assessment of prevalence and trends of indoor tanning use among US adolescents, to examine changes in the prevalence of indoor tanning use from 1998 to 2004 in relation to state policies on minors' access, and to assess the prevalence of burns, rashes, and infections among users.

METHODS:

Two cross‐sectional population‐based surveys of US youths ages 11 to 18 years and their parents/guardians conducted in 1998 (N = 1196) and 2004 (N = 1613) used identical questions to assess use of indoor tanning and correlates of this behavior.

RESULTS:

The prevalence of indoor tanning use by adolescents within the past year changed little from 1998 to 2004 (10% to 11%). In states with policies regarding minors' access to indoor tanning, the prevalence stayed the same or decreased from 1998 to 2004, whereas it increased in states without such policies. Neither trend was found to be statistically significant. Youth tanning attitudes, parental indoor tanning use, and parents' permission were strongly associated with youth use of indoor tanning. Fifty‐eight percent of users reported burns from indoor tanning.

CONCLUSIONS:

The presence of state legislation restricting minors' access to indoor tanning appears to have limited effectiveness, perhaps because most states' policies permit use with parental consent. Multipronged approaches are needed to reduce indoor tanning use in youths. Cancer 2009. Published 2008 by the American Cancer Society.
Hydrogen Molecules Trapped in Interstitial Host Channels of α‐Hydroquinone
Authors: Yoon Ji‐Ho , Lee Yun‐Je , Park Jeasung , Kawamura Taro , Yamamoto Yoshitaka , Komai Takeshi , Takeya Satoshi , Han Sang Sup , Lee Jong‐Won , Lee Yongjae
Published: December 2008

Easy come, easy go: Hydroquinone forms a channel structure of cages with hydrogen‐bonded hexagons. These may provide an ideal route for the fast inclusion and facile release of hydrogen molecules (see figure), which can lead to reversible hydrogen storage under mild conditions.

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Vaporisation of a Dicationic Ionic Liquid
Authors: Lovelock Kevin R. J. , Deyko Alexey , Corfield Jo‐Anne , Gooden Peter N. , Licence Peter , Jones Robert G.
Published: December 2008

Highest heat of vaporization yet: The dicationic ionic liquid [C3(C1Im)2][Tf2N]2 evaporates as a neutral ion triplet. These neutral ion triplets can then be ionised to form singly and doubly charged ions. The mass spectrum exhibits the dication attached to one remaining anion, and the naked dication itself (see picture).

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Analysis and modeling of growing budding yeast populations at the single cell level
Authors: Porro Danilo , Vai Marina , Vanoni Marco , Alberghina Lilia , Hatzis Christos
Published: December 2008

Model organisms and in particular the budding yeast Saccharomyces cerevisiae have been instrumental in advancing our understanding of cell cycle progression. The asymmetric division of the budding yeast and the tight coupling between cell growth and division have challenged the theoretical understanding of the cell size structure of growing yeast populations. Past efforts have centered on modeling the steady‐state theoretical age distribution for asymmetric division from which a cell size distribution can be derived assuming dispersion of cell size within each age class. Different developments, especially in the field of flow cytometry, allowed the determination of a number of cellular properties and their joint distributions for the entire population and the different subpopulations as well. A new rigorous framework for modeling directly the dynamics of size distributions of structured yeast populations has been proposed, which readily extends to modeling of more complex conditions, such as transient growth. Literature on the structure of growing yeast populations and modeling of cell cycle progression is reviewed. © 2008 International Society for Advancement of Cytometry
Cancer therapeutics: reflections on natural killer cells
Authors: Gurwitz David
Published: December 2008

Cancer remains a leading cause of death globally, including in developing countries. In spite of the introduction of several new drugs to the anti‐cancer arsenal in recent years, including monoclonal antibodies and selective tyrosine kinase inhibitors blocking the action of cancer‐promoting hormones, full remission remains exceptional in many common cancers including lung, pancreas, and stomach cancers. One aspect of cancer therapeutics that remains mostly neglected is developing drugs for promoting the capacity of the innate immune system, most notably the natural killer cells, to recognize and destroy cancer cells. Minimizing the inhibition of natural killer cells' cytotoxic activity by current cancer therapeutics also deserves further consideration in cancer research. Better understanding of the physiology of the immune cells, in particular of factors regulating the action and differentiation of natural killer cells and their migration into tumor tissues, seems worthy of more in‐depth research toward developing new cancer drugs. In this context, the potential of selective cannabinoid receptor agonists and fatty acid amid hydrolase inhibitors as immune‐enhancing drugs deserves extra attention. Drug Dev Res 69:285–288, 2008. © 2008 Wiley‐Liss, Inc.
New cancer drugs targeting the biosynthesis of estrogens and androgens
Authors: Poirier Donald
Published: December 2008

The enzymes involved in the synthesis of steroids are very interesting therapeutic targets. By reducing the levels of androgens and estrogens that stimulate the proliferation of cancer cells, a potent and selective inhibitor of a key‐steroidogenic enzyme may become an alternative or a complementary strategy to the use of an antiandrogen or an antiestrogen for the treatment of prostate cancer or breast and endometrial cancers, respectively. Five enzymes, namely 17α‐hydroxylase 17α‐lyase, aromatase, 17β‐hydroxysteroid dehydrogenases, 5α‐reductases, and steroid sulfatase were especially studied and found to be interesting targets for the development of inhibitors as potential cancer drugs. The present review will summarize the role of these five enzymes and their inhibitors with a special highlight about the molecules more recently reported in the literature and exhibiting dual therapeutic action. Drug Dev Res 69:304–318, 2008. © 2008 Wiley‐Liss, Inc.
Top NOTCH targets: notch signaling in cancer
Authors: Jun H. Toni , Stevens Jennitte , Kaplan‐Lefko Paula
Published: December 2008

The evolutionarily conserved Notch signaling pathway controls diverse events such as cell fate determination, proliferation, apoptosis, and stem cell maintenance. Dysregulation of this pathway has been implicated as a causative event in multiple cancers, including T‐cell acute lymphoblastic leukemia (T‐ALL), where mutation of Notch1 occurs in >50% of patients. Although mutation has not been observed in solid tumors, changes in expression of ligands and receptors, as well as pathway modulators, may play a role in pathogenesis. More recent evidence suggests that Notch signaling is also critical in tumor angiogenesis. We review the data that support the development of therapeutics to target the Notch pathway for the treatment of cancer. Drug Dev Res 69:319–328, 2008. © 2008 Wiley‐Liss, Inc.
Integrin αvβ3‐targeted cancer therapy
Authors: Liu Zhaofei , Wang Fan , Chen Xiaoyuan
Published: December 2008

Anti‐angiogenesis is a promising strategy for the treatment of cancer. Integrins, consisting of two noncovalently bound transmembrane α and β subunits, are an important molecular family involved in tumor angiogenesis. The blockade of integrin signaling has been demonstrated to be efficient to inhibit tumor growth, angiogenesis, and metastasis. Among all the integrins, αvβ3 seems to be the most important one during tumor angiogenesis. The inhibition of integrin αvβ3 signaling with antibodies, peptides, peptidomimetics, and other antagonists has great potential in the treatment of cancer. In addition, integrin αvβ3 is highly expressed on activated endothelial cells, new‐born vessels as well as some tumor cells, but is not present in resting endothelial cells and most normal organ systems, making it a suitable target for anti‐angiogenic therapy. In this article we will review the role of integrin αvβ3 in angiogenesis, present recent progress in the use of integrin αvβ3 antagonists and integrin‐targeted delivery systems as potential cancer therapeutics, and discuss future perspectives. Drug Dev Res 69:329–339, 2008. © 2008 Wiley‐Liss, Inc.
EGFR inhibition in the treatment of non‐small cell lung cancer
Authors: Gerber David E.
Published: December 2008

Epidermal growth factor receptor (EGFR) inhibitors have introduced the concept of targeted therapy to the treatment of non‐small cell lung cancer (NSCLC). These agents appear most effective in patients with tumors that are highly dependent on EGFR signaling pathways, a population that disproportionately includes females, nonsmokers, individuals of East Asian origin, and patients with adenocarcinoma histology. Currently available EGFR‐inhibiting drugs include the tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib, and lapatinib, which are administered orally and interfere with the intracellular tyrosine kinase domain, and the monoclonal antibodies (mAbs) cetuximab and panitumumab, which are administered intravenously and interfere with extracellular ligand binding. While the use of EGFR TKIs as monotherapy prolongs survival in metastatic NSCLC, they have demonstrated no benefit when added to conventional, cytotoxic chemotherapy. In contrast, the anti‐EGFR mAb cetuximab appears most effective when combined with chemotherapy or radiation. Despite dramatic initial responses to treatment in some cases, NSCLC eventually becomes resistant to EGFR inhibition. Possible mechanisms include secondary mutations that interfere with drug binding, oncogenic pathways driven by other receptor tyrosine kinases, and independent activity of downstream signaling molecules. Efforts to overcome such resistance include irreversibly binding EGFR TKIs, multi‐targeted TKIs, and combinations with chemotherapy, radiation, and other targeted therapies. Drug Dev Res 69:359–372, 2008 © 2008 Wiley‐Liss, Inc.
Summary of ‘Continuous heparin infusion to prevent thrombosis and catheter occlusion in neonates with peripherally placed percutaneous central venous catheters’
Authors: Shah P. S. , Shah V. S.
Published: December 2008

This is a summary of a Cochrane review, published in this issue of EBCH, first published as: Shah PS, Shah VS. Continuous heparin infusion to prevent thrombosis and catheter occlusion in neonates with peripherally placed percutaneous central venous catheters. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD002772. DOI: 10.1002/14651858.CD002772.pub3.

Further information for this Cochrane review is available in this issue of EBCH in the accompanying Commentary and Characteristics and Key Findings Tables. Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration