bluuebunny/crossref_metadata_2025_split huggingface dataset:
N,N‐Dimethylaminopropylsilane: A Case Study on the Nature of Weak Intramolecular Si⋅⋅⋅N Interactions
Authors: Hagemann Michael , Berger Raphael J. F. , Hayes Stuart A. , Stammler Hans‐Georg , Mitzel Norbert W. 
Published: October 2008

AbstractN,N‐Dimethylaminopropylsilane H3Si(CH2)3NMe2was synthesised by the reaction of (MeO)3Si(CH2)3NMe2with lithium aluminium hydride. Its solid‐state structure was determined by X‐ray diffraction, which revealed a five‐membered ring with an Si⋅⋅⋅N distance of 2.712(2) Å. Investigation of the structure by gas‐phase electron diffraction (GED), ab initio and density functional calculations and IR spectroscopy revealed that the situation in the gas phase is more complicated, with at least four conformers present in appreciable quantities. Infrared spectra indicated a possible Si⋅⋅⋅N interaction in the SiH stretching region (2000–2200 cm−1), as the approach of the nitrogen atom in the five‐membered ring weakens the bond to the hydrogen atom in thetransposition. Simulated gas‐phase IR spectra generated from ab initio calculations (MP2/TZVPP) exhibited good agreement with the experimental spectrum. A method is proposed by which the fraction of the conformer with a five‐membered ring can be determined by a least‐squares fit of the calculated to experimental absorption intensities. The abundance of this conformer was determined as 23.7(6) %, in good agreement with the GED value of 24(6) %. The equilibrium Si⋅⋅⋅N distance predicted by theory for the gas‐phase structure was highly variable, ranging from 2.73 (MP2) to 3.15 Å (HF). The value obtained by GED is 2.91(4) Å, which could be confirmed by a scan of the potential‐energy surface at the DF‐LCCSD[T] level of theory. The nature of the weak dative bond in H3Si(CH2)3NMe2can be described in terms of attractive inter‐electronic correlation forces (dispersion) and is also interpreted in terms of the topology of the electron density.
Total Synthesis of Discodermolide: Optimization of the Effective Synthetic Route
Authors: de Lemos Elsa , Porée François‐Hugues , Bourin Arnaud , Barbion Julien , Agouridas Evangelos , Lannou Marie‐Isabelle , Commerçon Alain , Betzer Jean‐François , Pancrazi Ange , Ardisson Janick 
Published: October 2008

AbstractAn efficient and modulable total synthesis of discodermolide (DDM), a unique marine anticancer polyketide is described including related alternative synthetic approaches. Particularly notable is the repeated application of a crotyltitanation reaction to yield homoallylic (Z)‐O‐ene‐carbamate alcohols with excellent selectivity. Advantage was taken of this reaction not only for the stereocontrolled building of the syn–anti methyl–hydroxy–methyl triads of DDM, but also for the direct construction of the terminal (Z)‐diene. Of particular interest is also the installation of the C13C14 (Z)‐double bond through a highly selective dyotropic rearrangement. The preparation of the middle C8–C14 fragment in two sequential stages and its coupling to the C1–C7 moiety was a real challenge and required careful optimization. Several synthetic routes were explored to allow high and reliable yields. Due to the flexibility and robust character of this approach, it might enable a systematic structural variation of DDM and, therefore, the elaboration and exploration of novel discodermolide structural analogues.
Enantioselective determination of mexiletine and its metabolites p‐hydroxymexiletine and hydroxymethylmexiletine in rat plasma by normal‐phase liquid chromatography‐tandem mass spectrometry: Application to pharmacokinetics
Authors: Godoy Ana Leonor Pardo Campos , Parisi Caio Cesar , Marques Maria Paula , Coelho Eduardo Barbosa , Lanchote Vera Lucia 
Published: October 2008

AbstractMexiletine (MEX), hydroxymethylmexiletine (HMM) and p‐hydroxymexiletine (PHM) were analyzed in rat plasma by LC‐MS/MS. The plasma samples were prepared by liquid‐liquid extraction using methyl‐tert‐butyl ether as extracting solvent. MEX, HMM, and PHM enantiomers were resolved on a Chiralpak® AD column. Validation of the method showed a relative standard deviation (precision) and relative errors (accuracy) of less than 15% for all analytes studied. Quantification limits were 0.5 ng ml−1 for the MEX and 0.2 ng ml−1 for the HMM and PHM enantiomers. The validated method was successfully applied to quantify the enantiomers of MEX and its metabolites in plasma samples of rats (n = 6) treated with a single oral dose of racemic MEX. Chirality, 2009. © 2008 Wiley‐Liss, Inc.
Preparation of enantiopure (R)‐hydroxy metabolite of denbufylline using immobilized Lactobacillus kefiri DSM 20587 as a catalyst
Authors: Pȩkala Elżbieta , Burbiel Joachim C. , Müller Christa E. 
Published: October 2008

AbstractLactobacillus kefiri DSM 20587 cells were immobilized in calcium alginate and carrageenan. The immobilized cells were used as biocatalysts for the enantioselective reduction of the methyl ketone group of denbufylline to synthesize the enantiopure (R)‐hydroxy metabolite: (−)‐1,3‐dibutyl‐7‐((2′R)‐hydroxypropyl)‐1H‐purine‐2,6(3H,7H)‐dione (1). The experimental conditions for the biotransformation were optimized. As denbufylline is insoluble in aqueous media, the influence of cosolvents (dimethylsulfoxide (DMSO), acetonitrile) and different concentrations of each solvent in the reaction mixture on the yield and enantiomeric excess of the final biotransformation product was studied. The maximum biotransformation yield (96–98%) and highest enantioselectivity (96% ee) for the obtained metabolite were reached using DMSO as a cosolvent at a concentration of 7.5% (v/v) in the presence of L. kefiri immobilized either in calcium alginate or in carrageenan. The absolute configuration of the stereogenic center of 1 was determined by applying Mosher's method. Chirality 2009. © 2008 Wiley‐Liss, Inc.
Stereoselective pharmacokinetics of diniconazole enantiomers in rabbits
Authors: Wang Qiuxia , Qiu Jing , Zhou Zhiqiang , Cao Aocheng , Wang Xinquan , Zhu Wentao , Dang Ziheng 
Published: October 2008

AbstractDiniconazole [(E)‐(RS)‐1‐(2,4,‐dichlorophenyl)‐4,4‐dimethyl‐2‐(1H‐1,2,4‐triazole‐1‐yl)pent‐1‐en‐3‐ol)] is a potent triazole fungicide. The enantioselective pharmacokinetics of diniconazole enantiomers in rabbits was studied via intravenous (i.v.) injection. The pharmacokinetics and the enantiomer fraction (EF) were determined using normal high‐performance liquid chromatography with diode array detection and a cellulose‐tris‐(3,5‐dimethylphenylcarbamate)‐based chiral stationary phase (CDMPC‐CSP). The time–concentration curves in plasma were fitted by a two‐compartment open mode. The results showed that the concentration of S‐diniconazole in plasma decreased faster than that of R‐diniconazole, and EFs increased with time after administration of racemic diniconazole (rac‐diniconazole). The R‐/S‐enantiomer ratio of the area under the time–plasma concentration curve (AUC0–∞) after administration was 1.52. The total plasma clearance value of S‐enantiomer was 1.57‐fold higher than that of the R‐diniconazole. These results indicate substantial stereoselectivity in the kinetics of diniconazole enantiomers in rabbit. Chirality, 2009. © 2008 Wiley‐Liss, Inc.
Design and Synthesis of Potent and Selective Azaindole‐Based Rho Kinase (ROCK) Inhibitors
Authors: Schirok Hartmut , Kast Raimund , Figueroa‐Pérez Santiago , Bennabi Samir , Gnoth Mark J. , Feurer Achim , Heckroth Heike , Thutewohl Michael , Paulsen Holger , Knorr Andreas , Hütter Joachim , Lobell Mario , Münter Klaus , Geiß Volker , Ehmke Heimo , Lang Dieter , Radtke Martin , Mittendorf Joachim , Stasch Johannes‐Peter 
Published: October 2008

AbstractRho kinase plays a pivotal role in several cellular processes such as vasoregulation, making it a suitable target for the treatment of hypertension and related disorders. We discovered a new compound class of Rho kinase (ROCK) inhibitors containing a 7‐azaindole hinge‐binding scaffold tethered to an aminopyrimidine core. Herein we describe the structure–activity relationships elucidated through biochemical and functional assays. The introduction of suitable substituents at the 3‐position of the bicyclic moiety led to an increase in activity, which was required to design compounds with favorable pharmacokinetic profile. Azaindole32was identified as a highly selective and orally available ROCK inhibitor able to cause a sustained blood pressure reduction in vivo.
Improved fluorescence of indocyanine green in vitro and in vivo after simple cooling procedures
Authors: Boddington Sophie , Sutton Elizabeth J. , Jones Ella , Purcell Derk D. , Henning Tobias D. , Tavri Sidhartha , Meier Reinhard , Sista Akhilesh , Fu Yanjun , Daldrup‐Link Heike 
Published: October 2008

AbstractIndocyanine green (ICG) is a contrast agent used for detecting angiogenesis with optical imaging (OI). The purpose of this study was to investigate whether cooling procedures increase the signal yield of ICG with OI. Test samples of 0.05 and 0.02 mM ICG in 40% DMSO and 60% DMEM underwent OI at four different temperatures (5, 37, 55 and 75°C). In addition, six athymic rats with an antigen‐induced arthritis of the knee and ankle joints underwent OI before and after injection of ICG (10 mg/ml, dose 15 mg/kg) on two separate days with and without cooling of the joints. The fluorescent signals of the test samples and arthritic joints were measured and evaluated for significant differences before and after cooling with a t‐test. In vitro studies showed a strong negative correlation between ICG temperature and fluorescent signal. The mean fluorescent signal of arthritic joints (measured in efficiency) was 0.345 before ICG‐injection, 4.55 after ICG‐injection and before cooling and 9.71 after ICG‐injection and after cooling. The fluorescent signal enhancement of arthritic joints with ICG‐enhanced OI images increased significantly after cooling (p = 0.02). The signal yield of ICG can be significantly increased by cooling the target pathology. The primary underlying cause of the temperature dependence of ICG is enhanced collisional quenching with increasing temperature. This simple cooling method may be immediately helpful to increase the fluorescence signal yield in current ICG‐enhanced OI‐studies in patients. Copyright © 2008 John Wiley & Sons, Ltd.
Phase 2 trial of rituximab plus hyper‐CVAD alternating with rituximab plus methotrexate‐cytarabine for relapsed or refractory aggressive mantle cell lymphoma
Authors: Wang Michael , Fayad Luis , Cabanillas Fernando , Hagemeister Fredrick , McLaughlin Peter , Rodriguez Maria A , Kwak Larry W. , Zhou Yuhong , Kantarjian Hagop , Romaguera Jorge 
Published: October 2008

AbstractBACKGROUND.Relapsed or refractory mantle cell lymphoma has a very poor prognosis. The authors evaluated the response rates and survival times of patients treated with an intense regimen known to be effective against untreated aggressive mantle cell lymphoma: rituximab plus hyper‐CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) alternating with rituximab plus methotrexate‐cytarabine.METHODS.In this prospective, open‐label, phase 2 study, patients received this combination for 6 to 8 cycles. Twenty‐nine patients were evaluable for response.RESULTS.The median number of cycles received was 5 (range, 1‐7 cycles), and the overall response rate was 93% (45% complete response [CR] or CR unconfirmed [CRu] and 48% partial response [PR]). All 5 patients previously resistant to treatment had a response (1 CR, 4 PR), and both patients whose disease did not change in response to prior therapy had PRs. Toxic events occurring in response to the 104 cycles given included neutropenic fever (11%), grade 3 or 4 neutropenia (74%), and grade 3 or 4 thrombocytopenia (63%). There were no deaths from toxicity. At a median follow‐up of 40 months (range, 5‐48 months), the median failure‐free survival time was 11 months with no plateau in the survival curve.CONCLUSIONS.This combination chemotherapy was effective for refractory/relapsed mantle cell lymphoma. Cancer 2008. © 2008 American Cancer Society.
Pathomorphologic evaluation of pulmonary radiofrequency ablation
Authors: Clasen Stephan , Krober Stefan‐Martin , Kosan Bora , Aebert Hermann , Fend Falko , Bomches Andrea , Claussen Claus D. , Pereira Philippe L. 
Published: October 2008

AbstractBACKGROUND.Radiofrequency (RF) ablation is an increasingly applied technique. Promising results of hepatic RF ablation raised expectations of its capabilities for treatment of primary and secondary lung tumors. Because of different thermal and electrical properties of lung tissue, compared with liver tissue, a simple analogy of tissue response is not possible. The authors aimed to evaluate the effectiveness of image‐guided pulmonary RF ablation and to characterize pathomorphology of tissue response.METHODS.RF ablations of 11 pulmonary malignancies in 9 patients were performed under computed tomography (CT)‐guidance. Three days after RF ablation, surgical resection was performed followed by pathologic examination. Specimens were evaluated macroscopically, histologically by hematoxylin and eosin (H & E) staining, terminal deoxy‐nucleotidyl transferase‐mediated nick end‐labeling (TUNEL), and electron microscopy.RESULTS.Tumor tissues and adjacent lung tissues were characterized by double‐strand fragmentation as determined by TUNEL. Ultrastructurally apoptotic bodies were found, indicating apoptotic cells. Criteria for tissue necrosis were not fulfilled by standard histological staining (H & E), showing preserved tissue architecture and only few microscopic cellular details suggestive of tumor regression. Because of DNA fragmentation, as determined by TUNEL and results from electron microscopy, the authors confirmed the tumor tissue to be completely ablated in 10 (90.9%) cases. However, in 2 cases, a safety margin was absent.CONCLUSIONS.CT‐guided pulmonary RF ablation of pulmonary malignancies is a locally effective treatment. Three days after RF ablation, tumor tissue seemed to be thermally fixed still showing characteristics of vital tumor tissue in standard histological staining; however the tissue proved to be in regression toward coagulative necrosis verified ultrastructurally and by TUNEL. Cancer 2008. © 2008 American Cancer Society.
Breast cancer survivors' health‐related quality of life
Authors: Paskett Electra D. , Alfano Catherine M. , Davidson Mario A. , Andersen Barbara L. , Naughton Michelle J. , Sherman Aurora , McDonald Paige Green , Hays Jennifer 
Published: October 2008

AbstractBACKGROUND.Small samples with few minority women and/or the absence of comparisons to peers without cancer histories have limited previous research suggesting racial differences in breast cancer survivors' health‐related quality of life (HRQoL). This study not only compared HRQoL of African American and white breast cancer survivors, but also compared the HRQoL of these women to that of same‐race women with no cancer history.METHODS.Data from the Women's Health Initiative‐Observational Study were used, including 5021 cancer survivors and 88,532 women without a history of cancer. Multivariate regression analyses estimated differences in breast cancer survivors' baseline HRQoL (RAND36), depressive symptoms (CES‐D short‐form), and sleep quality (WHIIRS).RESULTS.African American breast cancer survivors reported worse physical functioning and general health compared with white survivors. Among African Americans, survivors reported worse role limitations due to physical health, pain, general health, and vitality than women without a history of cancer. This was most evident in those with more recent diagnoses. Most significant differences between groups were small in magnitude (Cohen d = .21‐.36).CONCLUSIONS.These results add to the increasing knowledge of cancer disparities by showing that African American women have small, but clinically meaningful, decrements in physical HRQoL compared with white survivors and with African American women without cancer. Because African American women also face diagnosis with higher grade tumors and higher breast cancer mortality, more research is needed to examine the physical and psychosocial experiences of African American breast cancer survivors to elucidate the mechanisms leading to poorer outcomes. Cancer 2008. © 2008 American Cancer Society.
Patient‐reported measurements of oral mucositis in head and neck cancer patients treated with radiotherapy with or without chemotherapy
Authors: Elting Linda S. , Keefe Dorothy M. , Sonis Stephen T. , Garden Adam S. , Spijkervet F. K. L. , Barasch Andrei , Tishler Roy B. , Canty Thomas P. , Kudrimoti Mahesh K. , Vera‐Llonch Montserrat ,   for the Burden of Illness Head and Neck Writing Committee
Published: October 2008

AbstractBACKGROUND.The risk, severity, and patient‐reported outcomes of radiation‐induced mucositis among head and neck cancer patients were prospectively estimated.METHODS.A validated, patient‐reported questionnaire (OMDQ), the FACT quality of life (QOL), and the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scales were used to measure mucositis (reported as mouth and throat soreness), daily functioning, and use of analgesics. Patients were studied before radiotherapy (RT), daily during RT, and for 4 weeks after RT.RESULTS.Contrary to previous reports, the risk of mucositis was virtually identical in the 126 patients with oral cavity or oropharynx tumors (99% overall; 85% grade 3‐4) compared with 65 patients with tumors of the larynx or hypopharynx (98% overall; 77% grade 3‐4). The mean QOL score decreased significantly during RT, from 85.1 at baseline to 69.0 at Week 6, corresponding with the peak of mucositis severity. The mean functional status score decreased by 33% from 18.3 at baseline to 12.3 at Week 6. The impact of mucositis on QOL was proportional to its severity, although even a score of 1 or 2 (mild or moderate) was associated with a significant reduction in QOL (from 93.6 at baseline to 74.7 at Week 6). Despite increases in analgesic use from 34% at baseline to 80% at Week 6, mean mucositis scores exceeded 2.5 at Week 6.CONCLUSIONS.Mucositis occurs among virtually all patients who are undergoing radiation treatment of head and neck cancers. The detrimental effects on QOL and functional status are significant, and opioid analgesia provides inadequate relief. Preventive rather than symptom palliation measures are needed. Cancer 2008. © 2008 American Cancer Society.
Sustained delivery of NT‐3 from lens fiber cells in transgenic mice reveals specificity of neuroprotection in retinal degenerations
Authors: LaVail Matthew M. , Nishikawa Shimpei , Duncan Jacque L. , Yang Haidong , Matthes Michael T. , Yasumura Douglas , Vollrath Douglas , Overbeek Paul A. , Ash John D. , Robinson Michael L. 
Published: October 2008

AbstractSeveral neurotrophic factors (NTFs) are effective in protecting retinal photoreceptor cells from the damaging effects of constant light and slowing the rate of inherited photoreceptor degenerations. It is currently unclear whether, if continuously available, all NTFs can be protective for many or most retinal degenerations (RDs). We used transgenic mice that continuously overexpress the neurotrophin NT‐3 from lens fibers under the control of the αA‐crystallin promoter to test for neuroprotection in light‐damage experiments and in four naturally occurring or transgenically induced RDs in mice. Lens‐specific expression of NT‐3 mRNA was demonstrated both by in situ hybridization in embryos and by reverse‐transcriptase polymerase chain reaction (RT‐PCR) in adult mice. Furthermore, NT‐3 protein was found in abundance in the lens, ocular fluids, and retina by enzyme‐linked immunosorbent assay (ELISA) and immunocytochemistry. Overexpression of NT‐3 had no adverse effects on the structure or function of the retina for up to at least 14 months of age. Mice expressing the NT‐3 transgene were protected from the damaging effects of constant light to a much greater degree than those receiving bolus injections of NT‐3. When the NT‐3 transgene was transferred into rd/rd, Rds/+, Q344ter mutant rhodopsin or Mertk knockout mice, overexpression of NT‐3 had no protective effect on the RDs in these mice. Thus, specificity of the neuroprotective effect of NT‐3 is clearly demonstrated, and different molecular mechanisms are inferred to mediate the protective effect in light‐induced and inherited RDs. J. Comp. Neurol. 511:724–735, 2008. © 2008 Wiley‐Liss, Inc.
Cervical prephrenic interneurons in the normal and lesioned spinal cord of the adult rat
Authors: Lane Michael A. , White Todd E. , Coutts Marcella A. , Jones Alex L. , Sandhu Milapjit S. , Bloom David C. , Bolser Donald C. , Yates Bill J. , Fuller David D. , Reier Paul J. 
Published: October 2008

AbstractAlthough monosynaptic bulbospinal projections to phrenic motoneurons have been extensively described, little is known about the organization of phrenic premotor neurons in the adult rat spinal cord. Because interneurons may play an important role in normal breathing and recovery following spinal cord injury, the present study has used anterograde and transneuronal retrograde tracing to study their distribution and synaptic relations. Exclusive unilateral, first‐order labeling of the phrenic motoneuron pool with pseudorabies virus demonstrated a substantial number of second‐order, bilaterally distributed cervical interneurons predominantly in the dorsal horn and around the central canal. Combined transneuronal and anterograde tracing revealed ventral respiratory column projections to prephrenic interneurons, suggesting that some propriospinal relays exist between medullary neurons and the phrenic nucleus. Dual‐labeling studies with pseudorabies virus recombinants also showed prephrenic interneurons integrated with either contralateral phrenic or intercostal motoneuron pools. The stability of interneuronal pseudorabies virus labeling patterns following lateral cervical hemisection was then addressed. Except for fewer infected contralateral interneurons at the level of the central canal, the number and distribution of phrenic‐associated interneurons was not significantly altered 2 weeks posthemisection (i.e., the point at which the earliest postinjury recovery of phrenic activity has been reported). These results demonstrate a heterogeneous population of phrenic‐related interneurons. Their connectivity and relative stability after cervical hemisection raise speculation for potentially diverse roles in modulating phrenic function normally and postinjury. J. Comp. Neurol. 511:692–709, 2008. © 2008 Wiley‐Liss, Inc.
Comparative analysis of cadherin expression and connectivity patterns in the cerebellar system of ferret and mouse
Authors: Neudert Franziska , Krishna‐K.  , Nuernberger Monique , Redies Christoph 
Published: October 2008

AbstractThe cerebellum shows remarkable variations in the relative size of its divisions among vertebrate species. In the present study, we compare the cerebella of two mammals (ferret and mouse) by mapping the expression of three cadherins (cadherin‐8, protocadherin‐7, and protocadherin‐10) at similar postnatal stages. The three cadherins are expressed differentially in parasagittal stripes in the cerebellar cortex, in the portions of the deep cerebellar nuclei, in the divisions of the inferior olivary nucleus, and in the lateral vestibular nucleus. The expression profiles suggest that the cadherin‐positive structures are interconnected. The expression patterns resemble each other in ferret and mouse, although some differences can be observed. The general resemblance indicates that cerebellar organization is based on a common set of embryonic divisions in the two species. Consequently, the large differences in cerebellar morphology between the two species are more likely caused by differential growth of these embryonic divisions than by differences in early embryonic patterning. Based on the cadherin expression patterns, a model of corticonuclear projection territories in ferret and mouse is proposed. In summary, our results indicate that the cerebellar systems of rodents and carnivores display a relatively large degree of similarity in their molecular and functional organization. J. Comp. Neurol. 511:736–752, 2008. © 2008 Wiley‐Liss, Inc.