bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct Assessments of the Antioxidant Effects of Propofol Medium Chain Triglyceride/Long Chain Triglyceride on the Brain of Stroke-prone Spontaneously Hypertensive Rats Using Electron Spin Resonance Spectroscopy
Authors: Kobayashi Kyo , Yoshino Fumihiko , Takahashi Shun-Suke , Todoki Kazuo , Maehata Yojiro , Komatsu Tomoko , Yoshida Kazu-Ichi , Lee Masaichi-Chang-Il
Published: August 2008

Background

Antioxidant anesthetics such as propofol (2,6-diisopropylphenol) directly inhibit lipid peroxidation via the generation of reactive oxygen species. Currently, there are no other studies regarding the direct effects of propofol medium chain triglyceride/long chain triglyceride (MCT/LCT) on reactive oxygen species generation or in experimental models of reactive oxygen species-induced oxidative stress in the brain.

Methods

The authors investigated the effects of propofol MCT/LCT on reactive oxygen species (hydroxyl radical or superoxide) by electron spin resonance spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide. The effects of propofol MCT/LCT on oxidative stress in the brain of Wistar-Kyoto rats or stroke-prone spontaneously hypertensive rats were investigated by using an in vivo L-band electron spin resonance system to monitor the decay rate of 3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl as a nitroxyl spin probe.

Results

These studies provided direct evidence that propofol MCT/LCT inhibited hydroxyl radical generation, but not superoxide generation. Regarding the hydroxyl radical from the Fenton system, it is likely to be due to the scavenging effects of vehicle. Anesthesia with propofol MCT/LCT reduced the degree of the high oxidative stress in the brain of stroke-prone spontaneously hypertensive rats.

Conclusion

The current data show that propofol, mixed with clinical reagents (propofol MCT/LCT), resulted in the down-regulation of high oxidative stress due to scavenging hydroxyl radical, as demonstrated by in vitro or in vivo electron spin resonance analysis. These results led to reduced levels of hydroxyl radical, formed by brain injury such as stroke, and may therefore provide advantages for neuroprotection during anesthesia for craniotomy, e.g., in cases of brain disease.
Using Permutation Entropy to Measure the Electroencephalographic Effects of Sevoflurane
Authors: Li Xiaoli , Cui Suyuan , Voss Logan J.
Published: August 2008

Background

Approximate entropy (AE) has been proposed as a measure of anesthetic drug effect in electroencephalographic data. Recently, a new method called permutation entropy (PE) based on symbolic dynamics was also proposed to measure the complexity in an electroencephalographic series. In this study, the AE and PE were applied to electroencephalographic recordings for revealing the effect of sevoflurane on brain activity. The dose-response relation of PE during sevoflurane anesthesia was compared with that of AE.

Methods

Nineteen patients' electroencephalographic data were collected during the induction of general anesthesia with sevoflurane. PE and AE were applied to the electroencephalographic recordings, and the performance of both measures was assessed by pharmacokinetic-pharmacodynamic modeling and prediction probability. To ensure an accurate complexity measure of electroencephalographic recordings, a wavelet-based preprocessor was built in advance.

Results

Both PE and AE could distinguish between the awake and anesthetized states and were highly correlated to each other (r = 0.8, P = 0.004). The pharmacokinetic-pharmacodynamic model adequately described the dose-response relation between PE and AE and sevoflurane effect site concentration. The coefficient R between PE and effect site concentration was 0.89 +/- 0.07 for all patients, compared with 0.60 +/- 0.14 for AE. Prediction probabilities of 0.86 +/- 0.04 and 0.79 +/- 0.09 for PE and AE showed that PE has a stronger ability to differentiate between the awake and anesthetic states.

Conclusion

The results show that PE can estimate the sevoflurane drug effect more effectively than AE. This method could be applied to design a new electroencephalographic monitoring system to estimate sevoflurane anesthetic drug effect.
Novel Ryanodine Receptor Mutation That May Cause Malignant Hyperthermia
Authors: Kaufmann Alexius , Kraft Birgit , Michalek-Sauberer Andrea , Weigl Lukas G.
Published: August 2008

Background

Malignant hyperthermia (MH) is a hypermetabolic condition caused by a genetic disposition leading to increased Ca release from the sarcoplasmic reticulum after exposure to triggering agents. In the authors' ongoing evaluation of patients undergoing MH testing in Austria, they detected a family with a new variant of the ryanodine receptor 1. Guidelines suggest that genetic tests are possible only for individuals from families in which the mutations are known. The aim of this study was to provide functional data that establish a potential link between this new variant and susceptibility to MH, and thus enable application in genetic tests.

Methods

Messenger RNA was isolated from skeletal muscle cells grown in culture and used for synthesis of complementary DNA, which served as a template for 23 polymerase chain reactions. The sequences of all reaction products were analyzed. Functional studies in differentiated muscle cells included the Ca releasing activity of caffeine and 4-chloro-m-cresol. The authors measured the intracellular Ca concentration and, in combined patch clamp-Ca detection experiments, the voltage dependence of the Ca release.

Results

In a single family, the authors found a transition from a highly conserved thymine to cysteine at position 11953, leading to the exchange of tryptophan to arginine at position 3985. This variant was absent in 100 MH-nonsusceptible individuals. Functionally, cells carrying this variant were more sensitive to caffeine and 4-chloro-m-cresol than wild-type cells and showed a shift in the voltage-dependent Ca release to more negative potentials.

Conclusion

These data document a role of the new W3985R variant in MH susceptibility.
Low-tidal-volume Mechanical Ventilation Induces a Toll-like Receptor 4–dependent Inflammatory Response in Healthy Mice
Authors: Vaneker Michiel , Joosten Leo A. , Heunks Leo M. A. , Snijdelaar Dirk G. , Halbertsma Feico J. , van Egmond Jan , Netea Mihai G. , van der Hoeven Johannes G. , Scheffer Gert Jan
Published: August 2008

Background

Mechanical ventilation (MV) can induce ventilator-induced lung injury. A role for proinflammatory pathways has been proposed. The current studies analyzed the roles of Toll-like receptor (TLR) 4 and TLR2 involvement in the inflammatory response after MV in the healthy lung.

Methods

Wild-type (WT) C57BL6, TLR4 knockout (KO), and TLR2 KO mice were mechanically ventilated for 4 h. Bronchoalveolar lavage fluid was analyzed for presence of endogenous ligands. Lung homogenates were used to investigate changes in TLR4 and TLR2 expression. Cytokines were measured in lung homogenate and plasma, and leukocytes were counted in lung tissue.

Results

MV significantly increased endogenous ligands for TLR4 in bronchoalveolar lavage fluid and relative messenger RNA expression of TLR4 and TLR2 in lung tissue. In lung homogenates, MV in WT mice increased levels of keratinocyte-derived chemokine, interleukin (IL)-1alpha, and IL-1beta. In TLR4 KO mice, MV increased IL-1alpha but not IL-1beta, and the increase in keratinocyte-derived chemokine was less pronounced. In plasma, MV in WT mice increased levels of IL-6, keratinocyte-derived chemokine, and tumor necrosis factor alpha. In TLR4 KO mice, MV did not increase levels of IL-6 or tumor necrosis factor alpha, and the response of keratinocyte-derived chemokine was less pronounced. MV in TLR2 KO mice did not result in different cytokine levels compared with WT mice. In WT and TLR2 KO mice, but not in TLR4 KO mice, MV increased the number of pulmonary leukocytes.

Conclusions

The current study supports a role for TLR4 in the inflammatory reaction after short-term MV in healthy lungs. Increasing the understanding of the innate immune response to MV may lead to future treatment advances in ventilator-induced lung injury, in which TLR4 may serve as a therapeutic target.
Perineural Administration of Dexmedetomidine in Combination with Bupivacaine Enhances Sensory and Motor Blockade in Sciatic Nerve Block without Inducing Neurotoxicity in Rat
Authors: Brummett Chad M. , Norat Mary A. , Palmisano John M. , Lydic Ralph
Published: August 2008

Background

The current study was designed to test the hypothesis that high-dose dexmedetomidine added to local anesthetic would increase the duration of sensory and motor blockade in a rat model of sciatic nerve blockade without causing nerve damage.

Methods

Thirty-one adult Sprague-Dawley rats received bilateral sciatic nerve blocks with either 0.2 ml bupivacaine, 0.5%, and 0.5% bupivacaine plus 0.005% dexmedetomidine in the contralateral extremity, or 0.2 ml dexmedetomidine, 0.005%, and normal saline in the contralateral extremity. Sensory and motor function were assessed by a blinded investigator every 30 min until the return of normal sensory and motor function. Sciatic nerves were harvested at either 24 h or 14 days after injection and analyzed for perineural inflammation and nerve damage.

Results

High-dose dexmedetomidine added to bupivacaine significantly enhanced the duration of sensory and motor blockade. Dexmedetomidine alone did not cause significant motor or sensory block. All of the nerves analyzed had normal axons and myelin at 24 h and 14 days. Bupivacaine plus dexmedetomidine showed less perineural inflammation at 24 h than the bupivacaine group when compared with the saline control.

Conclusion

The finding that high-dose dexmedetomidine can safely improve the duration of bupivacaine-induced antinociception after sciatic nerve blockade in rats is an essential first step encouraging future studies in humans. The dose of dexmedetomidine used in this study may exceed the sedative safety threshold in humans and could cause prolonged motor blockade; therefore, future work with clinically relevant doses is necessary.
Intracarotid Delivery of Drugs
Authors: Joshi Shailendra , Meyers Phillip M. , Ornstein Eugene
Published: August 2008

The major efforts to selectively deliver drugs to the brain in the past decade have relied on smart molecular techniques to penetrate the blood-brain barrier, whereas intraarterial drug delivery has drawn relatively little attention. Meanwhile, rapid progress has been made in the field of endovascular surgery. Modern endovascular procedures can permit highly targeted drug delivery by the intracarotid route. Intracarotid drug delivery can be the primary route of drug delivery or it could be used to facilitate the delivery of smart neuropharmaceuticals. There have been few attempts to systematically understand the kinetics of intracarotid drugs. Anecdotal data suggest that intracarotid drug delivery is effective in the treatment of cerebral vasospasm, thromboembolic strokes, and neoplasms. Neuroanesthesiologists are frequently involved in the care of such high-risk patients. Therefore, it is necessary to understand the applications of intracarotid drug delivery and the unusual kinetics of intracarotid drugs.
Radiofrequency Applications to Dorsal Root Ganglia
Authors: Malik Khalid , Benzon Honorio T. , Warner David S. , Warner Mark A.
Published: August 2008

Application of radiofrequency currents to the dorsal root ganglia, in the treatment of various pain syndromes, has been clinically practiced for more than 30 yr. The clinical efficacy and the safety of this technique, however, remain poorly understood. The authors reviewed the literature on this modality of pain relief to determine its clinical efficacy, safety, and mechanisms of action. The two modalities in common clinical use were pulsed and continuous mode radiofrequency. These techniques were generally found to be safe, and the majority of the observational studies reported their clinical efficacy. Five randomized controlled trials evaluated their clinical use; these trials were relatively short-termed and small in size, and their results were variable. The mechanism of action of these techniques was unclear. Larger controlled clinical trials evaluating the long-term effects of these techniques and basic science research to determine their precise mode of action are needed.
Identification of cis-acting sites for condensin loading onto budding yeast chromosomes
Authors: D’Ambrosio Claudio , Schmidt Christine Katrin , Katou Yuki , Kelly Gavin , Itoh Takehiko , Shirahige Katsuhiko , Uhlmann Frank
Published: August 2008

Eukaryotic chromosomes reach their stable rod-shaped appearance in mitosis in a reaction dependent on the evolutionarily conserved condensin complex. Little is known about how and where condensin associates with chromosomes. Here, we analyze condensin binding to budding yeast chromosomes using high-resolution oligonucleotide tiling arrays. Condensin-binding sites coincide with those of the loading factor Scc2/4 of the related cohesin complex. The sites map to tRNA and other genes bound by the RNA polymerase III transcription factor TFIIIC, and ribosomal protein and SNR genes. An ectopic B-box element, recognized by TFIIIC, constitutes a minimal condensin-binding site, and TFIIIC and the Scc2/4 complex promote functional condensin association with chromosomes. A similar pattern of condensin binding is conserved along fission yeast chromosomes. This reveals that TFIIIC-binding sites, including tRNA genes, constitute a hitherto unknown chromosomal feature with important implications for chromosome architecture during both interphase and mitosis.
Tumorigenic activity and therapeutic inhibition of Rheb GTPase
Authors: Mavrakis Konstantinos J. , Zhu Hong , Silva Ricardo L.A. , Mills John R. , Teruya-Feldstein Julie , Lowe Scott W. , Tam Wayne , Pelletier Jerry , Wendel Hans-Guido
Published: August 2008

The AKT–mTOR pathway harbors several known and putative oncogenes and tumor suppressors. In a phenotypic screen for lymphomagenesis, we tested candidate genes acting upstream of and downstream from mTOR in vivo. We find that Rheb, a proximal activator of mTORC1, can produce rapid development of aggressive and drug-resistant lymphomas. Rheb causes mTORC1-dependent effects on apoptosis, senescence, and treatment responses that resemble those of Akt. Moreover, Rheb activity toward mTORC1 requires farnesylation and is readily blocked by a pharmacological inhibitor of farnesyltransferase (FTI). In Pten-deficient tumor cells, inhibition of Rheb by FTI is responsible for the drug’s anti-tumor effects, such that a farnesylation-independent mutant of Rheb renders these tumors resistant to FTI therapy. Notably, RHEB is highly expressed in some human lymphomas, resulting in mTORC1 activation and increased sensitivity to rapamycin and FTI. Downstream from mTOR, we examined translation initiation factors that have been implicated in transformation in vitro. Of these, only eIF4E was able to enhance lymphomagenesis in vivo. In summary, the Rheb GTPase is an oncogenic activity upstream of mTORC1 and eIF4E and a direct therapeutic target of farnesyltransferase inhibitors in cancer.
Plant hormone receptors: new perceptions
Authors: Spartz Angela K. , Gray William M.
Published: August 2008

Plant growth and development require the integration of a variety of environmental and endogenous signals that, together with the intrinsic genetic program, determine plant form. Central to this process are several growth regulators known as plant hormones or phytohormones. Despite decades of study, only recently have receptors for several of these hormones been identified, revealing novel mechanisms for perceiving chemical signals and providing plant biologists with a much clearer picture of hormonal control of growth and development.
Genetic identification of yeast 18S rRNA residues required for efficient recruitment of initiator tRNAMet and AUG selection
Authors: Dong Jinsheng , Nanda Jagpreet S. , Rahman Hafsa , Pruitt Margaret R. , Shin Byung-Sik , Wong Chi-Ming , Lorsch Jon R. , Hinnebusch Alan G.
Published: August 2008

High-resolution structures of bacterial 70S ribosomes have provided atomic details about mRNA and tRNA binding to the decoding center during elongation, but such information is lacking for preinitiation complexes (PICs). We identified residues in yeast 18S rRNA critical in vivo for recruiting methionyl tRNAiMet to 40S subunits during initiation by isolating mutations that derepress GCN4 mRNA translation. Several such Gcd− mutations alter the A928:U1389 base pair in helix 28 (h28) and allow PICs to scan through the start codons of upstream ORFs that normally repress GCN4 translation. The A928U substitution also impairs TC binding to PICs in a reconstituted system in vitro. Mutation of the bulge G926 in h28 and certain other residues corresponding to direct contacts with the P-site codon or tRNA in bacterial 70S complexes confer Gcd− phenotypes that (like A928 substitutions) are suppressed by overexpressing tRNAiMet. Hence, the nonconserved 928:1389 base pair in h28, plus conserved 18S rRNA residues corresponding to P-site contacts in bacterial ribosomes, are critical for efficient Met-tRNAiMet binding and AUG selection in eukaryotes.
Aberrant Rheb-mediated mTORC1 activation and Pten haploinsufficiency are cooperative oncogenic events
Authors: Nardella Caterina , Chen Zhenbang , Salmena Leonardo , Carracedo Arkaitz , Alimonti Andrea , Egia Ainara , Carver Brett , Gerald William , Cordon-Cardo Carlos , Pandolfi Pier Paolo
Published: August 2008

The mammalian target of rapamycin (mTOR) represents a critical signaling crossroad where pathways commonly disrupted in cancer converge. We report here that Rheb GTPase, the upstream activator of the mTOR complex 1 (mTORC1) is amplified in human prostate cancers. We demonstrate that Rheb overexpression promotes hyperplasia and a low-grade neoplastic phenotype in the mouse prostate while eliciting a concomitant senescence response and a negative feedback loop limiting Akt activation. Importantly, we show that Pten haploinsufficiency cooperates with Rheb overexpression to markedly promote prostate tumorigenesis. We conclude that Rheb acts as a proto-oncogene in the appropriate genetic milieu and signaling context.
C. elegans dauer formation and the molecular basis of plasticity
Authors: Fielenbach Nicole , Antebi Adam
Published: August 2008

Because life is often unpredictable, dynamic, and complex, all animals have evolved remarkable abilities to cope with changes in their external environment and internal physiology. This regulatory plasticity leads to shifts in behavior and metabolism, as well as to changes in development, growth, and reproduction, which is thought to improve the chances of survival and reproductive success. In favorable environments, the nematode Caenorhabditis elegans develops rapidly to reproductive maturity, but in adverse environments, animals arrest at the dauer diapause, a long-lived stress resistant stage. A molecular and genetic analysis of dauer formation has revealed key insights into how sensory and dietary cues are coupled to conserved endocrine pathways, including insulin/IGF, TGF-β, serotonergic, and steroid hormone signal transduction, which govern the choice between reproduction and survival. These and other pathways reveal a molecular basis for metazoan plasticity in response to extrinsic and intrinsic signals.
Noncyclic Notch activity in the presomitic mesoderm demonstrates uncoupling of somite compartmentalization and boundary formation
Authors: Feller Juliane , Schneider Andre , Schuster-Gossler Karin , Gossler Achim
Published: August 2008

To test the significance of cyclic Notch activity for somite formation in mice, we analyzed embryos expressing activated Notch (NICD) throughout the presomitic mesoderm (PSM). Embryos expressing NICD formed up to 18 somites. Expression in the PSM of Hes7, Lfng, and Spry2 was no longer cyclic, whereas Axin2 was expressed dynamically. NICD expression led to caudalization of somites, and loss of Notch activity to their rostralization. Thus, segmentation and anterior–posterior somite patterning can be uncoupled, differential Notch signaling is not required to form segment borders, and Notch is unlikely to be the pacemaker of the segmentation clock.
Study of an RNA helicase implicates small RNA–noncoding RNA interactions in programmed DNA elimination in Tetrahymena
Authors: Aronica Lucia , Bednenko Janna , Noto Tomoko , DeSouza Leroi V. , Siu K.W. Michael , Loidl Josef , Pearlman Ronald E. , Gorovsky Martin A. , Mochizuki Kazufumi
Published: August 2008

Tetrahymena eliminates micronuclear-limited sequences from the developing macronucleus during sexual reproduction. Homology between the sequences to be eliminated and ∼28-nucleotide small RNAs (scnRNAs) associated with an Argonaute family protein Twi1p likely underlies this elimination process. However, the mechanism by which Twi1p–scnRNA complexes identify micronuclear-limited sequences is not well understood. We show that a Twi1p-associated putative RNA helicase Ema1p is required for the interaction between Twi1p and chromatin. This requirement explains the phenotypes of EMA1 KO strains, including loss of selective down-regulation of scnRNAs homologous to macronuclear-destined sequences, loss of H3K9 and K27 methylation in the developing new macronucleus, and failure to eliminate DNA. We further demonstrate that Twi1p interacts with noncoding transcripts derived from parental and developing macronuclei and this interaction is greatly reduced in the absence of Ema1p. We propose that Ema1p functions in DNA elimination by stimulating base-pairing interactions between scnRNAs and noncoding transcripts in both parental and developing new macronuclei.
Role of Failure Modes on Energy Absorption in Unidirectional PMC Tubes
Authors: Abdel-Haq M. , Newaz G. M.
Published: August 2008

The primary focus of this investigation was to study the effect of failure modes on key energy absorption parameters including the initial peak load ( Ppeak), the drop in the peak load and the sustained crushing load ( Pavg.) in the crushing process of unidirectional polymer matrix composite (PMC) tubes under quasi-static conditions. The failure modes of interest are the axial cracks, the transverse cracks and delamination. The roles of initiators with different radii and external constraints were carefully analyzed in the context of primary failure modes using a real time image acquisition system. The results for fiberglass/polyester tubes showed that the failure modes play a critical role on the load-deflection ( P-) response of the tubes and their corresponding specific energy absorption (SEA). In addition, it was possible to control the failure modes for better crushing performance by using external constraints combined with initiators.
Material Characterization of FGM Plates Using Elastic Waves and an Inverse Procedure
Authors: Liu G. R. , Han X. , Lam K. Y.
Published: August 2008

A computational inverse procedure is presented for characterization of the material properties of functionally graded materials (FGMs) using the surface displacement response of the plate. Amodified hybrid numerical method is first developed combining some existing techniques to compute the wave field in an FGM plate for given material properties and their variation in the thickness direction. The modified HNM allows a linear variation of material properties in the element in the thickness direction. This is to reduce the number of elements needed to model the material variation of FGM. The modified HNM is proven more efficient than the original HNM. The high efficiency paves the way for inverse procedure. The reconstruction of the material properties of FGM plates is performed using an inverse procedure of nonlinear least squares method. Numerical examples are presented to demonstrate the present procedure for material characterization of FGM plates. The present procedure can recover accurately the material properties of an FGM with an initial guess of up to 40% off from their true values.
The Influence of Embedded Optical Fibres on the Fatigue Damage Progress in Quasi-Isotropic CFRP Laminates
Authors: Surgeon M. , Wevers M.
Published: August 2008

Embedded optical fibre sensors have in the last decade been introduced as possible candidates for continuous damage monitoring in loaded composite structures. However, incorporation of foreign bodies like optical fibres in laminated structures can lead to substantial microstructural disturbances, stress concentrations and degradations in mechanical properties. Optical fibres were embedded in the different interfaces of a quasi-isotropic CFRP laminate which was subsequently tested in interrupted tension-tension fatigue. During each interruption the damage state of the samples was quantified by using penetrant enhanced microfocus radiography. The results were compared to earlier results obtained during continuous fatigue testing is which the number of cycles to fracture and the stiffness degradation were monitored. The main conclusion is that some optical fibre configurations can affect the fatigue properties by weakening the 0°-plies or accelerating the damage evolution. These results are the first to demonstrate a faster damage evolution caused by embedded optical fibres.
Fitting dynamical X-ray diffraction data over the World Wide Web
Authors: Stepanov Sergey , Forrest Rebecca
Published: August 2008

The first implementation of fitting X-ray Bragg diffraction profiles from strained multilayer crystals at a remote web-based X-ray software server is presented. The algorithms and the software solutions involved in the process are described. The suggested technology can be applied to a wide range of scientific research and has the potential to promote remote collaborations across scientific communities.
In situultra-small-angle X-ray scattering study of the solution-mediated formation and growth of nanocrystalline ceria
Authors: Allen Andrew J. , Hackley Vincent A. , Jemian Pete R. , Ilavsky Jan , Raitano Joan M. , Chan Siu-Wai
Published: August 2008

Results are presented for anin situsynchrotron-based ultra-small-angle X-ray scattering (USAXS) study of the solution-mediated formation and growth of nanocrystalline ceria (n-CeO2) using a new remote-controlled, isothermal, circulating fluid flow cell. The fluid flow mitigates or reduces X-ray beam-induced damage, air bubbles or particulate flocculation within the bulk solution, but prevents any coarse particulates that do form from settling out from suspension. Combined with the large-scale range accessible in USAXS studies, the flow cell has enabled measurement,in situand in real time, of structural characteristics from 10 Å to a few micrometres in size as a function of the changing physical and chemical conditions. By applying a multi-component model, the nanoparticle formation and growth component has been identified. Control and online monitoring of flow rate, temperature and pH suspension conditions have permitted real-time studies of the formation and growth of the individual n-CeO2particles from homogeneous dilute solution over several hours. Aspects of the nanoparticle nucleation and growth are revealed that have not been observed directly in measurements on this system.
4,4′-(Propane-1,3-diyl)dipiperidinium sulfate monohydrate
Authors: Yang E , Song Xu-Chun , Zhuang Rong-Qiang
Published: August 2008

In the title compound, C13H28N2
2+·SO4
2−·H2O, extensive hydrogen-bonding interactions between the protonated 4,4′-(propane-1,3-diyl)dipiperidinium ions, the sulfate anions and the water molecules lead to a three-dimensional pillared and layered structure with the 4,4′-(propane-1,3-diyl)dipiperidinium ions acting as the pillars.
1,4-Diazoniabicyclo[2.2.2]octane terephthalate
Authors: Yang E , Song Xu-Chun , Zhu Jian-Wei
Published: August 2008

In the title compound, C6H14N2+·C8H4O4
2−, the protonated 1,4-diazoniabicyclo[2.2.2]octane cations and the deprotonated terephthalate anions are alternately linked by N—H...O hydrogen bonds into chains.
4-Amino-3,5-di-2-pyridyl-4H-1,2,4-triazole
Authors: Ramos Silva Manuela , Silva Joana A. , Martins Nuno D. , Matos Beja Ana , Sobral Abilio J. F. N.
Published: August 2008

In the crystal structure of the title compound, C12H10N6, the molecules deviate slightly from planarity. The plane of the central triazole ring makes angles of 6.13 (9) and 3.28 (10)° with the pyridyl ring planes. Intramolecular N—H...N interactions form six-membered closed rings. The crystal packing also shows weak C—H...π and C—H...N interactions.
Bis(2,4,6-triamino-1,3,5-triazin-1-ium) bis(4-hydroxypyridine-2,6-carboxylato)cuprate(II) hexahydrate
Authors: Ramos Silva Manuela , Motyeian Elham , Aghabozorg Hossein , Ghadermazi Mohammad
Published: August 2008

In the title compound, (C3H7N6)2[Cu(C7H3NO5)2]·6H2O, the coordination geometry of the CuII atom can be described as distorted octahedral. The equatorial plane is defined by four O atoms from two 4-hydroxypyridine-2,6-dicarboxylate ligands. The axial positions are occupied by the N atoms of the same ligands. There is an extensive three-dimensional hydrogen-bond network reinforcing crystal cohesion.
(2,4-Dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylato-κ2
O
4,O
5)(4-oxido-2-oxo-1,2-dihydropyrimidine-5-carboxylato-κ2
O
4,O
5)bis(1,10-phenanthroline-κ2
N,N′)yttrium(III) dihydrate
Authors: Xiong Wei , Xing Huihui , Su Yan , Chen Zilu
Published: August 2008

In the title compound, [Y(C5H2N2O4)(C5H3N2O4)(C12H8N2)2]·2H2O, the YIII ion lies on a twofold rotation axis and exhibits a distorted square-antiprismatic coordination geometry. It is chelated by two 1,10-phenanthroline ligands, a 2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate monoanion and a 4-oxido-2-oxo-1,2-dihydropyrimidine-5-carboxylate dianion. The H atom involved in an N—H...N hydrogen bond between the 1,2-dihydropyrimidine units has half occupancy and is disordered around a twofold rotation axis.
(4-Oxido-2-oxo-1,2-dihydropyrimidine-5-carboxylato-κ2
O
4,O
5)(4-oxido-2-oxo-1,2-dihydropyrimidin-3-ium-5-carboxylato-κ2
O
4,O
5)bis(1,10-phenanthroline-κ2
N,N′)gadolinium(III) dihydrate
Authors: Xiong Wei , Xing Huihui , Su Yan , Chen Zilu
Published: August 2008

The title compound, [Gd(C5H2N2O4)(C5H3N2O4)(C12H8N2)2]·2H2O, was obtained from a solvothermal reaction of 2,4-dihydroxypyrimidine-5-carboxylic acid (H3iso), GdCl3·6H2O and 1,10-phenanthroline (phen). The GdIII ion is located on a twofold rotation axis and is coordinated by four N atoms from two chelating phen ligands and four O atoms (5-carboxylate and 4-oxido O atoms) from H2iso− and Hiso2− ligands. The molecules are linked into a three-dimensional network by N—H...O, N—H...N and O—H...O hydrogen bonds. The H atom involved in an N—H...N hydrogen bond is disordered around a twofold rotation axis with half occupancy.
3-(2-Hydroxyphenyl)-5-(2-methoxyphenyl)-1H-pyrazole
Authors: Hasan Aurangzeb , Ikram Sumera , Badshah Amir , Bolte Michael , Zia Mehwash
Published: August 2008

The title compound, C16H14N2O2, was derived from 1-(2-hydroxyphenyl)-3-(2-methoxyphenyl)propane-1,3-dione. The molecule is essentially planar (r.m.s. deviation for all non-H atoms = 0.089 Å). Two intramolecular hydrogen bonds stabilize the molecular conformation and one N—H...O hydrogen bond stabilizes the crystal structure.
(3aS,7S,9aS,9bR)-3a,6,6,9a-Tetramethyl-2-oxoperhydronaphtho[2,1-b]furan-7-yl acetate
Authors: Huang Qing-Chun , Li Bo-Gang , Xie Yi-Peng , Yu Kai-Bei , Zhang Guo-Lin
Published: August 2008

The title compound (common name: 3β-acetoxy-8-epi-sclareolide), C18H28O4, is a sclareolide derivative, which was synthesized from 9(11)-en-3β-acetoxy-8-epi-sclareolide. In the molecular structure, the two six-membered rings display chair conformations and the five-membered ring displays an envelope conformation. Weak intermolecular C—H...O hydrogen bonding is present in the crystal structure.
2-Methyl-3-phenylsulfonyl-5-propyl-1-benzofuran
Authors: Choi Hong Dae , Seo Pil Ja , Son Byeng Wha , Lee Uk
Published: August 2008

The title compound, C18H18O3S, was prepared by the oxidation of 2-methyl-3-phenylsulfanyl-5-propyl-1-benzofuran with 3-chloroperoxybenzoic acid. The phenyl ring makes a dihedral angle of 81.74 (6)° with the plane of the benzofuran fragment. The crystal structure is stabilized by C—H...π interactions between a methyl H atom and the phenyl ring of the phenylsulfonyl substituent from a neighbouring molecule, and by intermolecular C—H...O interactions.
Perchlorato[N,N,N′,N′-tetrakis(2-pyridylmethyl)cyclohexane-1,2-diamine]manganese(II) perchlorate
Authors: Hwang In-Chul , Ha Kwang
Published: August 2008

The asymmetric unit of the title compound, [Mn(ClO4)(C30H34N6)]ClO4, consists of a cationic [Mn(ClO4)(C30H34N6)]+ complex and a perchlorate anion. In the complex, the Mn2+ ion is seven-coordinated in an approximately pentagonal–bipyramidal environment by six N atoms from the hexadentate N,N,N′,N′-tetrakis(2-pyridylmethyl)cyclohexane-1,2-diamine (tpdach) ligand and one O atom from a perchlorate anion. The complex displays intermolecular π–π interactions between adjacent pyridine rings (centroid-to-centroid distance 4.133 Å). Moreover, there are weak intra- and intermolecular C—H...O hydrogen bonds. The Cl atom and two O atoms of the perchlorate are disordered, with a site-occupancy factor of 0.59 (2) for the major component.
Bis(μ-biphenyl-2,2′-dicarboxylato)bis[(2,2′-bipyridine)copper(II)]
Authors: Guo Hong-Xu , Liang Min , Lin Bin , Wang Qing-Hua , Li Xi-Zhong
Published: August 2008

The title compound, [Cu2(C14H8O4)2(C10H8N2)2], is a centrosymmetric binuclear copper(II) complex, with a Cu...Cu separation of 6.136 (16) Å. The Cu atom displays a cis-CuN2O2 square-planar geometry, although two long (> 2.43 Å) Cu...O contacts complete a distorted cis-CuN2O4 octahedron. Extensive C—H...O hydrogen bonds link the molecules into a three-dimensional network.
BaCo2(AsO4)2
Authors: Đordević Tamara
Published: August 2008

Suitable single crystals of the title compound, barium dicobalt(II) bis[orthoarsenate(V)], were prepared under hydrothermal conditions. This phase belongs to a series of compounds with general formula AM
2(XO4)2, where A = alkaline earth metal, M = Mg or a divalent first-row transition element, and X = P, As or V. BaCo2(AsO4)2 is isotypic with BaNi2(XO4)2 (X = P, V or As) and is characterized by brucite-like sheets of edge-sharing CoO6 octahedra (3 symmetry) parallel to (001), with one-third of the octahedral positions being vacant. The sheets are capped above and below by AsO4 tetrahedra (3 symmetry) and are interconnected by distorted BaO12 cuboctahedra (\overline{3} symmetry).
N,N′-Bis[(E)-2-Benzylidenepropylidene]ethane-1,2-diamine
Authors: Khalaji Aliakbar Dehno , Ng Seik Weng
Published: August 2008

The two independent molecules in the asymmetric unit of the title Schiff base, C22H24N2, lie across centers of inversion. The C=N double bonds are in a trans configuration.
N-(2-Hydroxyphenyl)-4-nitrophthalimide
Authors: Mansor Shahirah , Zakaria Norzalida , Ariffin Azhar , Ng Seik Weng
Published: August 2008

Molecules of the title compound, C14H8N2O5, are linked by a hydroxy–amide O—H...O hydrogen bond into a linear chain. The hydroxy group is disordered over two positions of the benzene ring in an approximate 0.57:0.43 ratio.
N′-[1-(2-Hydroxy-5-methylphenyl)ethylidene]benzenesulfonohydrazide
Authors: Laila Musalem , Ali Hapipah M. , Puvaneswary Subramaniam , Robinson Ward T. , Ng Seik Weng
Published: August 2008

The two independent molecules in the asymmetric unit of the title compound, C15H16N2O3S, are each linked by an N—H...Osulfonyl hydrogen bond into a linear chain that runs along the shortest axis of the triclinic unit cell. The hydroxy groups are engaged in intramolecular hydrogen bonding and the amino N atom shows pyramidal coordination.
{5,5′-Dihydroxy-2,2′-[o-phenylenebis(nitrilomethylidyne)]diphenolato}nickel(II) dihydrate
Authors: Fun Hoong-Kun , Kia Reza , Mirkhani Valiollah , Zargoshi Hasan
Published: August 2008

In the title complex, [Ni(C20H14N2O4)]·2H2O, the NiII ion is in an essentially square-planar geometry involving an N2O2 atom set of the tetradentate Schiff base ligand. The Ni atom lies on a crystallographic twofold rotation axis. The asymmetric unit contains one half-molecule of the complex and a water molecule. An intermolecular O—H...O hydrogen bond forms a four-membered ring, producing an R
1
2(4) ring motif involving a bifurcated hydrogen bond to the phenolate O atoms of the complex molecule. In the crystal structure, molecules are linked by π–π stacking interactions, with centroid–centroid distances in the range 3.5750 (11)–3.7750 (11) Å. As a result of the twofold symmetry, the central benzene ring makes the same dihedral angle of 15.75 (9)° with the two outer benzene rings. The dihedral angle between the two hydroxyphenyl rings is 13.16 (5)°. In the crystal structure, molecules are linked into infinite one-dimensional chains by directed four-membered O—H...O—H interactions along the c axis and are further connected by C—H...O and π–π stacking into a three-dimensional network. An interesting feature of the crystal structure is the short Ni...O, O...O and N...N interactions which are shorter than the sum of the van der Waals radii of the relevant atoms. The crystal structure is stabilized by intermolecular O—H...O and C—H...O hydrogen bonds and by π–π stacking interactions.
Methyl 6-methoxycarbonylmethyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate
Authors: Kettmann Viktor , Světlík Jan , Veizerová Lucia
Published: August 2008

The title compound, C15H16N2O5, belongs to the class of monastrol-type anti-cancer agents and was selected for crystal structure determination in order to determine the conformational details needed for subsequent structure–activity relationship studies. The central tetrahydropyrimidine ring has a flat-envelope conformation. The 4-phenyl group occupies a pseudo-axial position and is inclined at an angle of ca 90° to the mean plane of the heterocyclic ring. Of the two methyl ester groups, one (in the 5-position) is in a coplanar and the other (in the 6-position) in a perpendicular orientation with respect to the heterocyclic plane. The coplanar 5-ester group has its carbonyl bond oriented cis with respect to the pyrimidine C=C double bond. By comparison of the structural results for the present compound with those determined previously for its diethyl analogue, we have identified the molecular factors which control the dual course of the Biginelli reaction with salicylaldehyde. The crystal structure is dominated by two hydrogen bonds which link the molecules into chains of dimers.
Aquadipicrato(tetraethylene glycol)gadolinium(III) picrate methanol hemisolvate
Authors: Kusrini Eny , Saleh Muhammad Idiris , Kia Reza , Fun Hoong-Kun
Published: August 2008

The asymmetric unit of the title compound [systematic name: aquabis(2,4,6-trinitrophenolato)(3,6,9-trioxaundecane-1,11-diol)gadolinium(III) 2,4,6-trinitrophenolate methanol hemisolvate], [Gd(C6H2N3O7)2(C8H18O5)(H2O)](C6H2N3O7)·0.5CH4O, contains two crystallographically independent GdIII complex cations with two uncoordinated picrate anions and one methanol molecule. Each GdIII atom has nine coordination sites occupied by five O atoms of tetraethylene glycol as a pentadentate ligand, one O atom of a water molecule and three O atoms of the two picrate anions as bidentate and monodentate ligands. The geometry is distorted tricapped trigonal prismatic. The mean planes of the two coordinated mono- and bidentate picrate ligands to the GdIII center are almost perpendicular to each other, as indicated by the dihedral angles of 89.92 (8) and 86.60 (8)° in the two complex cations. The ions are arranged in a two-dimensional network parallel to the ac plane. Short O...O and N...O contacts between the nitro groups, intramolecular C—H...O hydrogen bonds, intermolecular O—H...O, O—H...N and C—H...O hydrogen bonds, and two π–π interactions between benzene rings [centroid–centroid distances = 3.8073 (10)–3.9831 (10) Å] are observed. The methanol solvent molecule is disordered over two positions, with site-occupancy factors of ca 0.6 and 0.4.
Different pathotypes of the sunflower downy mildew pathogen Plasmopara halstedii all contain isometric virions†
Authors: HELLER‐DOHMEN MARION , GÖPFERT JENS C. , HAMMERSCHMIDT RAY , SPRING OTMAR
Published: August 2008

Eight pathotypes of Plasmopara halstedii were screened to investigate the occurrence of virions and the potential viral influence on the pathogenicity of the sunflower downy mildew pathogen. In 23 of 26 P. halstedii isolates derived from eight countries in Europe, North America and South America, virions were detected by transmission electron microscopy. By contrast, there were no ultrastructural indications of virus‐like particles in eight other related Oomycetes. The virions of representative P. halstedii isolates were morphologically and biochemically characterized and compared among each other. Regardless of their host's pathotypes, the geographical origin of the isolate and the sensitivity towards the fungicide metalaxyl, the viral characters obtained were uniform. The virions were isometric and measured approximately 37 nm in diameter. One polypeptide of c. 36 kDa and two segments of single‐stranded RNA (3.0 and 1.6 kb) were detected. Both viral RNA segments were detected by capillary electrophoresis in the three remaining P. halstedii isolates where virions were undetectable by transmission electron microscopy. Virus‐specific primers for the 1.6 kb‐segment were synthesized and used to determine and compare a partial sequence of the viral coat protein among virions of different P. halstedii pathotypes. In all tested isolates, fragments of 0.7 kb were amplified which were directly sequenced. Sequence variation was insignificant. As both less aggressive and more aggressive P. halstedii isolates contained virions, the presence or absence of virions could not explain the diverse aggressiveness of the downy mildew pathogen towards sunflower. Moreover, the results indicated that pathogenicity of P. halstedii was not related to variation in morphological or biochemical characters of the virions.
Evaluation of the pharmacokinetics of digoxin in healthy subjects receiving etoricoxib
Authors: Schwartz Jules I. , Agrawal Nancy G. B. , Wehling Martin , Musser Bret J. , Gumbs Carol P. , Michiels Nicole , De Smet Marina , Wagner John A.
Published: August 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Digoxin is a well‐recognized inotropic agent with a narrow therapeutic index.

• Nonsteroidal anti‐inflammatory drugs, including the selective cyclooxygenase‐2 inhibitor etoricoxib, are very likely to be used in patients receiving digoxin due to the similar populations requiring the drugs.

• Digoxin drug interactions should be assessed and described to clinicians when new drugs become available.

WHAT THIS STUDY ADDS

• This study is the first to provide the practitioner with a detailed description of the influence of etoricoxib on the pharmacokinetics of digoxin.

• Due to the methods used, it shows that etoricoxib does not interfere with P‐glycoprotein in the kidney, a method of digoxin disposition.

• In addition, this paper provides confidence to the practitioner that there will be no clinically important reason to avoid the combination of the two drugs.

AIMS

Digoxin is a commonly prescribed cardiac glycoside with a narrow therapeutic index. The aim was to investigate whether the cyclooxygenase‐2 selective nonsteroidal anti‐inflammatory drug etoricoxib affects the steady‐state pharmacokinetics of digoxin.

METHODS

This was a double‐blind, randomized, placebo‐controlled, two‐period cross‐over study. In each period, 14 healthy volunteers ranging in age from 21 to 35 years received oral digoxin 0.25 mg daily and were randomized to either etoricoxib 120 mg or matching placebo tablets once daily for 10 days. Trough digoxin plasma concentrations were analysed by linear regression to examine digoxin accumulation over time.

RESULTS

The geometric mean ratios (etoricoxib/placebo) for AUC0–24h, Cmax and urinary excretion were 1.06 (90% confidence interval 0.97, 1.17), 1.33 (1.21, 1.46) and 1.10 (1.00, 1.20), respectively. The median (range) for digoxin Tmax (h) values with etoricoxib and placebo were 0.5 (0.5, 1.5) and 1.0 (0.5, 1.5), respectively. Steady‐state digoxin plasma concentrations were achieved by day 7 in each treatment period. No serious adverse experiences were reported.

CONCLUSIONS

Although etoricoxib 120 mg did produce an approximately 33% increase in digoxin Cmax, this increase does not appear to be clinically meaningful, as cardiotoxicity with digoxin has been associated with elevations in steady‐state rather than peak concentrations. From these results, it appears that etoricoxib does not cause any changes in digoxin steady‐state pharmacokinetics that would necessitate a dose adjustment.
The effect of SLCO1B1 polymorphism on repaglinide pharmacokinetics persists over a wide dose range
Authors: Kalliokoski Annikka , Neuvonen Mikko , Neuvonen Pertti J. , Niemi Mikko
Published: August 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Organic anion transporting polypeptide 1B1 is an influx transporter expressed on the basolateral membrane of hepatocytes.

• A common single nucleotide polymorphism, c.521T→C (p.Val174Ala), of the SLCO1B1 gene has been associated with increased plasma repaglinide concentrations in healthy volunteers.

• Previous studies at low repaglinide doses have suggested that the effect of SLCO1B1 c.521T→C polymorphism on the pharmacokinetics of repaglinide could be dose‐dependent.

WHAT THIS STUDY ADDS

• Repaglinide peak plasma concentration and area under the plasma concentration–time curve increased linearly along with repaglinide dose ranging from 0.25 to 2 mg in both the predominant c.521TT and rare c.521CC genotype group.

• The effect of SLCO1B1 c.521T→C polymorphism on repaglinide pharmacokinetics persists over a wide dose range.

AIMS

To establish whether the effect of SLCO1B1[encoding organic anion transporting polypeptide 1B1 (OATP1B1)] c.521T→C (p.Val174Ala) polymorphism on the pharmacokinetics of repaglinide is dose‐dependent.

METHODS

Twelve healthy volunteers with the SLCO1B1 c.521TT genotype (controls) and eight with the c.521CC genotype ingested a single 0.25‐, 0.5‐, 1‐ or 2‐mg dose of repaglinide in a dose‐escalation study with a wash‐out period of ≥1 week.

RESULTS

The mean area under the plasma concentration–time curve from time 0 to infinity (AUC0–∞) of 0.25, 0.5, 1 or 2 mg repaglinide was 82% (95% confidence interval 47, 125), 72% (24, 138), 56% (24, 95) or 108% (59, 171) (P ≤ 0.001) larger in participants with the SLCO1B1 c.521CC genotype than in those with the c.521TT genotype, respectively. Repaglinide peak plasma concentration and AUC0–∞ increased linearly along with repaglinide dose in both genotype groups (r > 0.88, P < 0.001). There was a tendency towards lower blood glucose concentrations after repaglinide administration in the participants with the c.521CC genotype than in those with the c.521TT genotype.

CONCLUSIONS

The effect of SLCO1B1 c.521T→C polymorphism on the pharmacokinetics of repaglinide persists throughout the clinically relevant dose range.