bluuebunny/crossref_metadata_2025 huggingface dataset:
Directed Synthesis of a Heterobimetallic Complex Based on a Novel Unsymmetric Double‐Schiff‐Base Ligand: Preparation, Characterization, Reactivity and Structures of Hetero‐ and Homobimetallic Nickel(II) and Zinc(II) Complexes
Authors: Roth Arne , Buchholz Axel , Rudolph Manfred , Schütze Eileen , Kothe Erika , Plass Winfried
Published: December 2007

A series of bimetallic zinc(II) and nickel(II) complexes based on the novel dinucleating unsymmetric double‐Schiff‐base ligand benzoic acid [1‐(3‐{[2‐(bispyridin‐2‐ylmethylamino)ethylimino]methyl}‐2‐hydroxy‐5‐methylphenyl)methylidene]hydrazide (H2bpampbh) has been synthesized and structurally characterized. The metal centers reside in two entirely different binding pockets provided by the ligand H2bpampbh, a planar tridentate [ONO] and a pentadentate [ON4] compartment. The utilized ligand H2bpampbh has been synthesized by condensation of the single‐Schiff‐base proligand Hbpahmb with benzoic acid hydrazide. The reaction of H2bpampbh with two equivalents of either zinc(II) or nickel(II) acetate yields the homobimetallic complexes [Zn2(bpampbh)(μ,η1‐OAc)(η1‐OAc)] (ZnZn) and [Ni2(bpampbh)(μ‐H2O)(η1‐OAc)(H2O)](OAc) (NiNi), respectively. Simultaneous presence of one equivalent zinc(II) and one equivalent nickel(II) acetate results in the directed formation of the heterobimetallic complex [NiZn(bpampbh)(μ,η1‐OAc)(η1‐OAc)] (NiZn) with a selective binding of the nickel ions in the pentadentate ligand compartment. In addition, two homobimetallic azide‐bridged complexes [Ni2(bpampbh)(μ,η1‐N3)]ClO4 (NiNi(N3)) and [Ni2(bpampbh)(μ,η1‐N3)(MeOH)2](ClO4)0.5(N3)0.5 (NiNi(N3)(MeOH)2) were synthesized. In all complexes, the metal ions residing in the pentadentate compartment adopt a distorted octahedral coordination geometry, whereas the metal centers placed in the tridentate compartment vary in coordination number and geometry from square‐planar (NiNi(N3)) and square‐pyramidal (ZnZn and NiZn), to octahedral (NiNi and NiNi(N3)(MeOH)2). In the case of complex NiNi(N3) this leads to a mixed‐spin homodinuclear nickel(II) complex. All compounds have been characterized by means of mass spectrometry as well as IR and UV/Vis spectroscopies. Magnetic susceptibility measurements show significant zero‐field splitting for the nickel‐containing complexes (D=2.9 for NiZn, 2.2 for NiNi(N3), and 0.8 cm−1 for NiNi) and additionally a weak antiferromagnetic coupling (J=−1.4 cm−1) in case of NiNi. Electrochemical measurements and photometric titrations reveal a strong Lewis acidity of the metal center placed in the tridentate binding compartment towards external donor molecules. A significant superoxide dismutase reactivity against superoxide radicals was found for complex NiNi.
Emergence is coupled to scope, not level
Authors: Ryan Alex J.
Published: December 2007

Since its application to systems, emergence has been explained in terms of levels of observation. This approach has led to confusion, contradiction, and incoherence. When the concept of level is replaced by a framework of scope, resolution and state, this confusion is dissolved. We find that emergent properties are determined by the relationship between the scope of macrostate and microstate descriptions. This is formally demonstrated with mathematical examples, including the nonorientable, one sided and one edged emergent properties of the Mbius strip. Emergent properties are identified as nonlocal, because of spatially or temporally extended structure. This establishes normative definitions of emergent properties and emergence, which make sense of previous descriptive definitions of emergence. The central insight that emergence is coupled to scope means that emergence is objective, in the sense that it is independent of the knowledge of the observer. This framework is then used to identify fundamental limits to our ability to capture emergence in formal systems, and propose an alternative approach towards identifying system boundaries.© 2007 Wiley Periodicals, Inc. Complexity, 2007
Chemoenzymatic Synthesis and Chemical Recycling of Sustainable Polyurethanes
Authors: Yanagishita Yoshio , Kato Makoto , Toshima Kazunobu , Matsumura Shuichi
Published: December 2007

Two novel types of chemically recyclable ester‐containing polyurethanes, namely, a diol‐diacid‐type poly(diester‐urethane) (PDEU) and a hydroxy acid type poly(ester‐urethane) (PEU), were prepared by a green synthetic route that avoids the use of hazardous diisocyanate. The urethane linkage was introduced by the reaction of ethylene carbonate with amino alcohols and amino acids to form urethanediol and urethane‐containing hydroxy acids, respectively. The urethanediol underwent polymerization with dimethyl adipate in the presence of lipase to produce a high‐molecular‐weight PDEU, while PEU was prepared by the lipase‐catalyzed direct polycondensation of the urethane‐containing hydroxy acid monomer. The periodic introduction of ester linkages into the polyurethane chain afforded primary biodegradation points and chemically recyclable segments. Both PDEU and PEU were readily degraded in the presence of lipase into oligomers which were readily repolymerized in the presence of the same enzyme.
Photochemical Conversion of Solar Energy
Authors: Balzani Vincenzo , Credi Alberto , Venturi Margherita
Published: December 2007

Energy is the most important issue of the 21st century. About 85 % of our energy comes from fossil fuels, a finite resource unevenly distributed beneath the Earth’s surface. Reserves of fossil fuels are progressively decreasing, and their continued use produces harmful effects such as pollution that threatens human health and greenhouse gases associated with global warming. Prompt global action to solve the energy crisis is therefore needed. To pursue such an action, we are urged to save energy and to use energy in more efficient ways, but we are also forced to find alternative energy sources, the most convenient of which is solar energy for several reasons. The sun continuously provides the Earth with a huge amount of energy, fairly distributed all over the world. Its enormous potential as a clean, abundant, and economical energy source, however, cannot be exploited unless it is converted into useful forms of energy. This Review starts with a brief description of the mechanism at the basis of the natural photosynthesis and, then, reports the results obtained so far in the field of photochemical conversion of solar energy. The “grand challenge” for chemists is to find a convenient means for artificial conversion of solar energy into fuels. If chemists succeed to create an artificial photosynthetic process, “…︁ life and civilization will continue as long as the sun shines!”, as the Italian scientist Giacomo Ciamician forecast almost one hundred years ago.
Unintentional parathyroidectomy during total thyroidectomy
Authors: Manouras Andreas , Markogiannakis Haridimos , Lagoudianakis Emmanuel , Antonakis Pantelis , Genetzakis Michael , Papadima Artemis , Konstantoulaki Eleftheria , Papanikolaou Dimitrios , Kekis Panagiotis
Published: December 2007

Background.

Unintentional parathyroidectomy during thyroidectomy has been evaluated in a few studies. Moreover, the impact of the surgeon's experience and operative technique has not been evaluated. Our aim was to identify the incidence of unintentional parathyroidectomy during total thyroidectomy, its clinical consequences, and factors affecting its occurrence.

Methods.

We reviewed all total thyroidectomies during a 2‐year period. Patients were categorized into 2 groups: those with unintentional parathyroidectomy (parathyroidectomy group) and those without unintentional parathyroidectomy (no‐parathyroidectomy group).

Results.

Incidental parathyroidectomy occurred in 100 (19.7%) of the 508 patients. The groups were comparable in age, thyroid weight and pathology, operative time, surgeon experience (high/low volume), operative technique (suture‐ligation, LigaSure, or Ultracision), postoperative calcium, and transient hypocalcemia. No permanent hypocalcemia occurred. However, 11% of the parathyroidectomy group was men compared with 22% of the no‐parathyroidectomy group (p =.002).

Conclusions.

Unintentional parathyroidectomy, although common, has no clinical consequences. Unlike surgeon's experience and operative technique, patient sex was the only factor affecting its occurrence. © 2007 Wiley Periodicals, Inc. Head Neck, 2008
The impact of absenteeism on the quality of assembly line production: The importance of a specialization requirement
Authors: Mateo Ricardo
Published: December 2007

Absenteeism among manual workers is without doubt one of the most significant factors that affect the functioning of assembly lines. It is a widely held view that high levels of absenteeism have negative repercussions on the quality and costs of operations. According to the scientific theory of work, workers who temporarily stand in for their absent colleagues affect production quality levels because of a lack of work specialization and experience. However, new and sophisticated automation can eliminate the effect of absenteeism on assembly line production. This article gathered more than 960,000 products produced by different levels of absenteeism. The effects of absenteeism on the quality of products in assembly lines over the course of one year were analyzed. In contrast to established thinking, the empirical evidence presented here confirms that absenteeism does not always produce problems in the quality of products. This evidence can be explained by the need for specialization among manual workers has been reduced by the invention of more sophisticated and specialized machinery. © 2007 Wiley Periodicals, Inc.
Esophageal cancer and body mass index: Results from a prospective study of 220,000 men in China and a meta‐analysis of published studies
Authors: Smith Margaret , Zhou Maigeng , Whitlock Gary , Yang Gonghuan , Offer Alison , Hui Gei , Peto Richard , Huang Zhengjing , Chen Zhengming
Published: December 2007

Several epidemiological studies have reported on the association between body mass index (BMI) and risk of esophageal cancer, but these were mostly in Western populations where many are overweight or obese. There is little direct evidence about the relationship in China where the mean BMI is relatively low and the disease rate is high. We examined the data from a population‐based prospective study of 220,000 Chinese men aged 40–79 without a previous history of cancer (mean BMI 21.7 kg/m2), which included 1,082 esophageal cancer deaths during 10 years of follow‐up. Adjusted hazard ratios for death from esophageal cancer by baseline BMI category were calculated using Cox proportional hazards models. Even among men with good self‐assessed health and BMI ≥ 18.5 kg/m2, there was a strong inverse association between BMI and death from esophageal cancer, with each 5 kg/m2higher BMI associated with 25% (95%CI: 11–36%) lower esophageal cancer mortality. This inverse association persisted when analysis was restricted to men who had never smoked or when the first 5 years of follow‐up were excluded. The strength of the relationship was consistent with the pooled estimate for squamous cell carcinoma of the esophagus in a meta‐analysis of prospective studies (31% lower relative risk per 5 kg/m2higher BMI; 95% CI: 25–37%), but contrasted with that for adenocarcinoma which showed a positive association with BMI. Together, these data provide reliable evidence that in many populations low BMI is associated with an increased risk of squamous cell carcinoma of the esophagus. © 2007 Wiley‐Liss, Inc.
Interaction between antioxidant vitamin supplementation and cigarette smoking during radiation therapy in relation to long‐term effects on recurrence and mortality: A randomized trial among head and neck cancer patients
Authors: Meyer François , Bairati Isabelle , Fortin André , Gélinas Michel , Nabid Abdenour , Brochet François , Têtu Bernard
Published: December 2007

There has been concern that the efficacy of radiation therapy may be reduced when patients smoke or take antioxidant vitamins during treatment. Cancer prevention trials with beta carotene supplements documented adverse effects only among smokers. We conducted a randomized trial with alpha tocopherol (400 IU/day) and beta carotene (30 mg/day) supplements among 540 head and neck cancer (HNC) patients treated by radiation therapy. We examined whether smoking during radiation therapy modified the effects of the supplementation on HNC recurrence and on mortality. During the follow‐up, 119 patients had a HNC recurrence and 179 died. Cox models were used to test the interaction between smoking and supplementation and to estimate the hazard ratios (HR) for HNC recurrence and death associated with the supplementation. Cigarette smoking either before or after radiation therapy did not modify the effects of the supplementation. In contrast, the interactions between supplementation and cigarette smoking during radiation therapy were statistically significant for HNC recurrence (p = 0.03), all‐cause mortality (p = 0.02) and mortality from the initial HNC (p = 0.04). Among cigarette smokers, the HR were 2.41 (95% CI: 1.25–4.64) for recurrence, 2.26 (95% CI: 1.29–3.97) for all‐cause mortality and 3.38 (95% CI: 1.11–10.34) for HNC mortality. All corresponding HR among nonsmokers were close to 1. These results could best be explained by the hypothesis that the combined exposures reduced the efficacy of radiation therapy. Particular attention should be devoted to prevent patients from both smoking and taking antioxidant supplements during radiation therapy. © 2007 Wiley‐Liss, Inc.
The impact of tobacco smoking and alcohol drinking on survival of patients with non‐Hodgkin lymphoma
Authors: Talamini Renato , Polesel Jerry , Spina Michele , Chimienti Emanuela , Serraino Diego , Zucchetto Antonella , Zanet Ernesto , Franceschi Silvia , Tirelli Umberto
Published: December 2007

Tobacco smoking and alcohol consumption have not been clearly related to the risk of non‐Hodgkin lymphoma (NHL), and the impact of these two factors on survival of NHL patients has received little attention. Cases were 268 subjects with incident histologically‐confirmed NHL, admitted as inpatients to the Division of Medical Oncology, between 1983 and 2002. These individuals were enrolled as cases in case‐control studies conducted at the same institution over the same period. For all patients clinical (histological subtype, major prognostic factors and treatment) and epidemiological data (smoking and drinking habits) were available. Survival analysis was performed using Kaplan‐Meier methods. Hazard ratio (HR) was estimated by Cox proportional hazard model. Compared to never smokers, patients who smoked ≥20 cigarettes/day had higher risks of death (HR = 1.70, 95% confidence interval (CI): 1.06–2.73) and lower survivals at 5 years (60 and 46%, respectively). Likewise, patients who drunk ≥4 drinks/day showed 1.69‐fold higher probability of death (95% CI: 1.04–2.76) in comparison to drinkers of <2 drinks/day (5‐year survival: 47 and 67%, respectively). When combining exposure to alcohol and tobacco, no excess of death emerged in light drinkers (<4 drinks/day), irrespective of their smoking habits, but higher risks of death emerged among heavy drinkers. In the present study, heavy tobacco smoking, and particularly, heavy alcohol drinking were associated with poor survival in NHL patients. Our findings strongly encourage physicians to advice NHL patients to stop smoking and diminish alcohol consumption to obtain improvements in the course of NHL. © 2007 Wiley‐Liss, Inc.
Evidence that senescent human prostate epithelial cells enhance tumorigenicity: Cell fusion as a potential mechanism and inhibition by p16INK4a and hTERT
Authors: Bhatia Bobby , Multani Asha S. , Patrawala Lubna , Chen Xin , Calhoun‐Davis Tammy , Zhou Jianjun , Schroeder Lisa , Schneider‐Broussard Robin , Shen Jianjun , Pathak Sen , Chang Sandy , Tang Dean G.
Published: December 2007

Normal human prostate (NHP) epithelial cells undergo senescence in vitro and in vivo but the potential role of senescent NHP cells in prostate tumorigenesis remain unclear. Here we show that senescent NHP cells enhance the in vivo tumorigenicity of low‐tumorigenic LNCaP prostate cancer and low/non‐tumorigenic subset of cells (called L cells) isolated from multiple bulk‐cultured prostate (and other) cancer cell lines. Subsequent studies suggest cell–cell fusion as a potential mechanism for senescent NHP cell‐enhanced tumor development. Using fluorescently tagged tumor cells and/or NHP cells, we find that NHP cells, like fibroblasts, can undergo fusion with unfractionated tumor cells or the L cells. Using 293T‐L cells as the model cell system, we verify NHP and 293T‐L cell fusion by using differential RT‐PCR, karyotyping, and gene expression analyses. Further experiments demonstrate that senescent NHP cells that have lost progenitor markers, accumulated p16INK4a (p16) protein expression, and acquired the AR mRNA expression, appear to be the preferential fusion targets. Strikingly, the tumorigenicity of the NHP/293T‐L hybrid cells was inhibited by exogenous p16 as well as hTERT. Chromosomal analyses revealed that hTERT probably inhibited the in vivo tumorigenicity by maintaining genomic stability. These results suggest that senescent NHP cells, like senescent fibroblasts, may promote tumor development and that one of the mechanisms underlying the senescent NHP cell‐enhanced tumorigenicity could be through cell fusion. © 2007 Wiley‐Liss, Inc.
Does inhibition of degradation of hypoxia‐inducible factor (HIF) α always lead to activation of HIF? lessons learnt from the effect of proteasomal inhibition on HIF activity
Authors: Kaluz Stefan , Kaluzová Milota , Stanbridge Eric J
Published: December 2007

At the cellular level hypoxia induces transcriptional response that is mediated by the transcription factor hypoxia‐inducible factor (HIF). HIF is regulated at the level of its α subunit by 2‐oxoglutarate (2OG)‐dependent oxygenases that hydroxylate specific prolyl and asparaginyl residues of HIF‐α, affecting its stability and activity, respectively. In the presence of O2, the α subunit is degraded in a complex process with several distinct steps. In the first step, the degradation process is initiated by prolyl hydroxylases (PHDs). In the second step, the von Hippel‐Lindau (VHL)/E3 ligase complex recognizes the hydroxylated HIF‐α and mediates its polyubiquitylation by the ubiquitin‐conjugating enzyme E2. In the third step, the polyubiquitylated HIF‐α is translocated to the proteasome where it is degraded. Degradation of HIF‐α can be inhibited at any of the three levels either by various pharmacological inhibitors or due to inactivation of genes whose products regulate the HIF system. The emerging data about inactivation of HIF under conditions of proteasomal inhibition prompted us to provide an overview contrasting the outcome of inhibition at various stages of the degradative pathway for HIF activity. J. Cell. Biochem. 104: 536–544, 2008. © 2007 Wiley‐Liss, Inc.
Renal and carotid vascular resistance assessed with Doppler sonography
Authors: Ohta Yuko , Fujii Koji , Ibayashi Setsuro , Matsumura Kiyoshi , Tsuchihashi Takuya , Kitazono Takanari , Ooboshi Hiroaki , Kamouchi Masahiro , Hirakata Hideki , Ogata Toshiyasu , Kuroda Junya , Iida Mitsuo
Published: December 2007

Purpose

Resistance index (RI) is widely used for the evaluation of circulatory resistance and atherosclerosis with Doppler sonography, but differences in RI among vascular beds have not been fully elucidated. The present study was designed to evaluate the relationship between renal and carotid artery RI and to compare their relative risk factors for an increase in RI.

Methods

One hundred eighty‐five inpatients who underwent sonographic assessment of the renal and carotid arteries were enrolled in the study.

Results

Multivariate analyses revealed that age, pulse pressure (PP), and serum glucose level were positively correlated, whereas diastolic blood pressure (DBP) and creatinine clearance were negatively correlated with the RI of the interlobar arteries. Sex (male) and PP correlated positively, whereas DBP correlated negatively with the RI of the common carotid artery (CCA). The RI of the interlobar arteries was positively associated with that of the CCA, even after adjustment for major cardiovascular risk factors.

Conclusions

These findings suggest that RI of the renal and carotid arteries increase in parallel to a certain extent. On the other hand, risk factors for the increase of RI of the carotid and renal arteries differed in part, suggesting that specific control of respective risk factors may also be needed to prevent vascular damage in each vascular bed. © 2007 Wiley Periodicals, Inc. J Clin Ultrasound, 2008
MR angiography of the pedal arteries with gadobenate dimeglumine, a contrast agent with increased relaxivity, and comparison with selective intraarterial DSA
Authors: Kreitner Karl‐Friedrich , Kunz R. Peter , Herber Sascha , Martenstein Sonja , Dorweiler Bernhard , Dueber Christoph
Published: December 2007

Purpose

To compare gadobenate dimeglumine (Gd‐BOPTA)–enhanced MR angiography (i.e., contrast‐enhanced MRA [CE‐MRA]) of the pedal vasculature with selective digital subtraction angiography (DSA) in patients with peripheral arterial occlusive disease (PAOD).

Materials and Methods

A total of 22 patients with PAOD were prospectively examined at 1.5T. For contrast enhancement, 0.1 mmol/kg body weight of Gd‐BOPTA were applied. MRA consisted of dynamic imaging with acquisition of six consecutive data sets. Acquisition time for each data set was 24 seconds, voxel size was 1.0 × 1.0 × 1.3 mm3. A total of 20 out of 22 patient underwent selective DSA, two patients fine‐needle DSA. DSA and MRA were performed within seven days. Image analysis was independently done by two observers with assessment of overall image quality, motion artifacts, detection of patent vessel segments of the distal calf and pedal vessels, and the number of patent metatarsal arteries. After four weeks, a consensus reading of DSA images was done. A second consensus reading of CE‐MRA was performed after a further six weeks.

Results

Consensus readings of MRA and DSA revealed higher image quality and fewer motion artifacts for MRA (P = 0.021 and P = 0.008, respectively, sign test); interobserver agreement was good (κ = 0.78) for image quality, and moderate (κ = 0.46) for motion artifacts. There were no differences between CE‐MRA and DSA in detecting patent vessel segments with a high degree of agreement (κ = 0.89), and interobserver agreement for MRA was substantial (κ = 0.89). Significantly more vessels were assessed as partially occluded on DSA than on CE‐MRA (P = 0.004). There was a good agreement between DSA and CE‐MRA for assessment of relevant vessel stenosis (κ = 0.61); interobserver agreement for MRA was good (κ = 0.65). CE‐MRA detected significantly more patent metatarsal arteries than did DSA (P < 0.001).

Conclusion

Gd‐BOPTA–enhanced MRA is comparable to DSA for assessment of the pedal vasculature, and is able to delineate significantly more patent vessels without segmental occlusions and more metatarsal arteries than selective DSA. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Improvement in the reproducibility of region of interest using an auditory feedback loop: A pilot assessment using dynamic contrast‐enhanced (DCE) breast MR images
Authors: Chun Hee , Clymer Bradley , Sammet Steffen , Koch Regina M. , Stevens Robert , Knopp Michael V.
Published: December 2007

Purpose

To augment traditional visual data perception of complex multiparametric imaging data sets by adding auditory feedback to improve the delineation of regions of interest (ROIs) in tumor assessment in dynamic contrast‐enhanced (DCE) MRI.

Materials and Methods

In addition to conventional display methodologies, we have created an application window which interfaces with audio output using dynamically loadable sound modules, providing goodness of fit (GF) information through auditory feedback. We have assessed effectiveness of conveying sound information with three independent readers on eight DCE‐MR breast image data sets. The assessment was based on either conventional visual only mode or combined visual plus auditory mode. For statistical comparison between two sensory approaches, interobserver repeatability was measured with three different criteria.

Results

Adding auditory feedback improves repeatability significantly (P< 0.01), and the enhanced sensory approach had higher repeatability than visual only mode in visually complex breast tumor cases. However, in easy and moderate cases, visual only mode was more reproducible than the combined mode with very high significance (P< 0.001).

Conclusion

Adding auditory information to visual based image analysis for identifying tumor ROIs provides higher interobserver repeatability for analyzing complex multidimensional/multiparametric medical image data sets with visually difficult lesions to delineate. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Measurement of longitudinal (T1) relaxation in the human lung at 3.0 Tesla with tissue‐based and regional gradient analyses
Authors: Nichols Michael B. , Paschal Cynthia B.
Published: December 2007

Purpose

The purpose of this study is to measure the longitudinal (T1) relaxation time of human lung parenchyma at 3.0 Tesla (T), independent of large vessel signal, and to examine T1 as a function of position in gravitational, isogravitational, and radial planes.

Materials and Methods

Sixteen subjects were imaged. A series of 16–20 turbo field echo images was acquired over a 6‐s period after the application of a single nonselective inversion (180°) pulse. Tissue‐based segmentation was used to separate parenchymal tissue from large pulmonary vascular tissue in the resulting images. Time‐intensity curves for each tissue type were constructed and spin‐lattice relaxation time was determined by line‐fitting the time‐intensity curves. The lung slice was divided into 10 regions of interest in the gravitational, isogravitational, and radial directions and regional T1 versus position gradient analyses were performed.

Results

The T1 relaxation time of human lung parenchyma at 3.0T was determined to be 1374 ± 226 ms, while the T1 of blood in large pulmonary vessels was 1623 ± 236 ms. Whole lung T1 was found to be 1397 ± 214 ms. T1 of lung parenchyma was found to be significantly shorter than the T1 of blood in large pulmonary vessels and whole lung T1. No regional gradient was seen in the gravitational or isogravitational directions, but a significant gradient was seen in the radial direction. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Fragmentation of aromatic sulfonamides in electrospray ionization mass spectrometry: elimination of SO2 via rearrangement
Authors: Sun Mingjiang , Dai Wenning , Liu David Q.
Published: December 2007

Arylsulfonamides are attractive pharmacophores for drug candidates. Fragmentation behaviors of selected aromatic sulfonamides were investigated using electrospray ionization mass spectrometry in the positive ion mode. Some of the sulfonamides afforded unique loss of 64 (loss of SO2) ions upon collision‐induced dissociation followed by intramolecular rearrangements in the gas phase. This SO2 elimination‐rearrangement pathway leading to the generation of [M + H − SO2]+ ions appeared to be susceptible to substitutions on the aromatic (Ar) ring that would affect the Arsulfur bond strength and the stability of the partially positive charge developed at the ipso position upon bond dissociation. Electron withdrawing groups such as chlorine attached to the aromatic ring at ortho position seem to promote the SO2 extrusion. Although this fragmentation pathway in atmospheric pressure ionization MS is less predictable than in electron impact MS, it is a frequently encountered reaction. The absence of this fragmentation pathway in some of the arylsulfonamides indicates that other factors such as nucleophilicity of the nitrogen may also play a role in the process. With respect to the site of attachment of the migrating NR′R″, ipso‐substitution on the aromatic ring is evident since this fragmentation mechanism is operative in the fully ortho‐substituted arylsulfonamides. Copyright © 2007 John Wiley & Sons, Ltd.
Posaconazole (Noxafil, SCH 56592), a new azole antifungal drug, was a discovery based on the isolation and mass spectral characterization of a circulating metabolite of an earlier lead (SCH 51048)
Authors: Nomeir Amin A. , Pramanik Birendra N. , Heimark Larry , Bennett Frank , Veals John , Bartner Peter , Hilbert Maryjane , Saksena Anil , McNamara Paul , Girijavallabhan Viyyoor , Ganguly Ashit K. , Lovey Raymond , Pike Russell , Wang Haiyan , Liu Yi‐Tsung , Kumari Pramila , Korfmacher Walter , Lin Chin‐Chung , Cacciapuoti Anthony , Loebenberg David , Hare Roberta , Miller George , Pickett Cecil
Published: December 2007

Posaconazole (SCH 56592) is a novel triazole antifungal drug that is marketed in Europe and the United States under the trade name ‘Noxafil’ for prophylaxis against invasive fungal infections. SCH 56592 was discovered as a possible active metabolite of SCH 51048, an earlier lead. Initial studies have shown that serum concentrations determined by a microbiological assay were higher than those determined by HPLC from animals dosed with SCH 51048. Subsequently, several animals species were dosed with 3H‐SCH 51048 and the serum was analyzed for total radioactivity, SCH 51048 concentration and antifungal activity. The antifungal activity was higher than that expected based on SCH 51048 serum concentrations, confirming the presence of active metabolite(s). Metabolite profiling of serum samples at selected time intervals pinpointed the peak that was suspected to be the active metabolite. Consequently, 3H‐SCH 51048 was administered to a large group of mice, the serum was harvested and the metabolite was isolated by extraction and semipreparative HPLC. LC‐MS/MS analysis suggested that the active metabolite is a secondary alcohol with the hydroxyl group in the aliphatic side chain of SCH 51048. All corresponding monohydroxylated diastereomeric mixtures were synthesized and characterized. The HPLC retention time and LC‐MS/MS spectra of the diastereomeric secondary alcohols of SCH 51048 were similar to those of the isolated active metabolite. Finally, all corresponding individual monohydroxylated diasteriomers were synthesized and evaluated for in vitro and in vivo antifungal potencies, as well as pharmacokinetics. SCH 56592 emerged as the candidate with the best overall profile. Copyright © 2007 John Wiley & Sons, Ltd.
Glutathione content as a potential mediator of the vulnerability of cultured fetal cortical neurons to ethanol‐induced apoptosis
Authors: Maffi Shivani Kaushal , Rathinam Mary Latha , Cherian Priscilla P. , Pate William , Hamby‐Mason Rhoda , Schenker Steven , Henderson George I.
Published: December 2007

Ethanol ingestion during pregnancy elicits damage to the developing brain, some of which appears to result from enhanced apoptotic death of neurons. A consistent characteristic of this phenomenon is a highly differing sensitivity to ethanol within specific neuron populations. One possible explanation for this “selective vulnerability” could be cellular variations in glutathione (GSH) homeostasis. Prior studies have illustrated that ethanol elicits apoptotic death of neurons in the developing brain, that oxidative stress may be an underlying mechanism, and that GSH can be neuroprotective. In the present study, both multiphoton microscopy and flow cytometry demonstrate a striking heterogeneity in GSH content within cortical neuron populations. Ethanol differentially elicits apoptotic death and oxidative stress in these neurons. When neuron GSH content is reduced by treatment with butathione sulfoxamine, the ethanol‐mediated enhancement of reactive oxygen species is exacerbated. Sorting of cells into high‐ and low‐GSH populations further exemplifies ethanol‐mediated oxidative stress whereby apoptotic indices are preferentially elevated in the low‐GSH population. Western blot analysis of the low‐GSH subpopulations shows higher ethanol‐mediated expression of active caspase 3 and 24‐kDa PARP‐1 fragments compared with the high‐GSH subpopulation. In addition, neuronal content of 4‐hydroxynonenal adducts is higher in low‐GSH neurons in response to ethanol. These studies suggest that GSH content is an important predictor of neuronal sensitivity to ethanol‐mediated oxidative stress and subsequent cell death. The data support the proposition that the differences in proapoptotic responses to ethanol within specific neuron populations reflect a heterogeneity of neuron GSH content. © 2007 Wiley‐Liss, Inc.
Postnatal developmental regulation of Bcl‐2 family proteins in brain mitochondria
Authors: Soane Lucian , Siegel Zachary T. , Schuh Rosemary A. , Fiskum Gary
Published: December 2007

Although it has been long recognized that the relative balance of pro‐ and antiapoptotic Bcl‐2 proteins is critical in determining the susceptibility to apoptotic death, only a few studies have examined the level of these proteins specifically at mitochondria during postnatal brain development. In this study, we examined the age‐dependent regulation of Bcl‐2 family proteins using rat brain mitochondria isolated at various postnatal ages and from the adult. The results indicate that a general down‐regulation of most of the proapoptotic Bcl‐2 proteins present in mitochondria occurs during postnatal brain development. The multidomain proapoptotic Bax, Bak, and Bok are all expressed at high levels in mitochondria early postnatally but decline in the adult. Multiple BH3‐only proteins, including direct activators (Bid, Bim, and Puma) and the derepressor BH3‐only protein Bad, are also present in immature brain mitochondria and are down‐regulated in the adult brain. Antiapoptotic Bcl‐2 family members are differentially regulated, with a shift from high Bcl‐2 expression in immature mitochondria to predominant Bcl‐xL expression in the adult. These results support the concept that developmental differences in upstream regulators of the mitochondrial apoptotic pathway are responsible for the increased susceptibility of cells in the immature brain to apoptosis following injury. © 2007 Wiley‐Liss, Inc.
Inflammation: A new candidate in modulating adult neurogenesis
Authors: Das Sulagna , Basu Anirban
Published: December 2007

Any pathological perturbation to the brain provokes a cascade of molecular and cellular events, which manifests in the form of microglial activation and release of various proinflammatory molecules. This eventually culminates in a profound neuroinflammatory reaction that characterizes the brain's response to stress, injury, or infection. The inflammatory cascade is an attempt by the system to eliminate the challenge imposed on the brain, clear the system of the dead and damaged neurons, and rescue the normal functioning of this vital organ. However, during the process of microglial activation, the proinflammatory mediators released exert certain detrimental effects, and neural stem cells and progenitor cells are likely to be affected. Here we review how the proliferation, maturation, and migration of the neural stem cells are modulated under such an inflammatory condition. The fate of the noncommitted neural stem cells and its differentiation potency are often under strict regulation, and these proinflammatory mediators seem to disrupt this critical balance and finely tune the neurogenesis pattern in the two niches of neurogenesis, the subventricular zone and the subgranular zone of the hippocampus. Moreover, the migration ability of these stem cells, which is important for localization to the proper site, is also affected in a major way by the chemokines released following inflammation. © 2007 Wiley‐Liss, Inc.
Multifaceted roles of sphingosine‐1‐phosphate: How does this bioactive sphingolipid fit with acute neurological injury?
Authors: Singh Indrapal N. , Hall Edward D.
Published: December 2007

Sphingosine‐1‐phosphate (Sph‐1‐P) is an essential bioactive sphingolipid metabolite that has currently become the focus of intense interest. Sph‐1‐P is generated by the enzyme sphingosine kinase (SphK) in response to diverse stimuli, including growth factors, cytokines, and G‐protein‐coupled receptor (GPCR) agonists. Its precursor, sphingosine (Sph), is produced from the precursor ceramide (Cer) via a ceramidase (CDase) that is released from membrane sphingomyelin (SPM) by sphingomyelinases (SMase). Accumulating evidence indicates that Sph‐1‐P is the key regulatory lipid involved in the metabolism of sphingolipids and is involved in the control of numerous aspects of cell physiology, including mitogenesis, differentiation, migration, and apoptosis. These actions of Sph‐1‐P are mediated by a family of high‐affinity S1P receptors, named S1P1–5, which are coupled differentially via Gi, Gq, G12/13, and Rho to multiple effector systems, including adenylate cyclase, phospholipases C (PLC) and D (PLD), extracellular‐signal‐regulated kinase, c‐Jun N‐terminal kinase, p38 mitogen‐activated protein kinase, and nonreceptor tyrosine kinases. In this Review, we accumulate available evidence implying that sphingolipid signaling may represent a novel neuroprotective target to counteract the pathophysiology of acute brain and spinal cord injury in regard to apoptotic cell death mechanisms, mitochondrial dysfunction, lipid hydrolysis, and oxidative damage mechanisms. Furthermore, we discuss how Sph‐1‐P agonist approaches might be expected to increase the resistance of the central nervous system to injury by promoting neurotrophic activity, neurogenesis, and angiogenesis. On the other hand, antagonists of certain Sph‐1‐P‐related activity might possess proregenerative effects via promotion of neurite growth and inhibition of astrogliotic scarring. © 2007 Wiley‐Liss, Inc.
Local organization of water and its effect on the structural heterogeneities in room‐temperature ionic liquid/H2O mixtures
Authors: Fazio B. , Triolo A. , Di Marco G.
Published: December 2007

Fourier‐transform infrared and Raman spectroscopies have been used to investigate the role played by water on the structural organization of 1‐butyl‐3‐methyl‐imidazolium tetrafluoroborate and H2O mixtures, over a wide composition range at room temperature. Our measurements provide clear experimental evidence of the prompt association between ‘free’ water molecules and anions at very small water contents. Moreover, in the case of higher water contents, we obtain indications of the local aggregation of water molecules in the network. Such an aggregation is found to occur even before the saturation of all the anions that are available for H‐bonding. We propose that the water clusters favour the organization of ionic liquid in the polar network, where they are embedded, and the aggregation of hydrophobic alkyl tails in a micelle‐like structure. When mixtures with water molar fraction exceeding 0.7 are considered, this local organization starts to weaken owing to the gradual break up of the ion‐pair interactions. Copyright © 2007 John Wiley & Sons, Ltd.
Raman spectroscopic study of the uranyl carbonate mineral voglite
Authors: Frost Ray L. , Čejka Jiří , Ayoko Godwin A. , Dickfos Marilla J.
Published: December 2007

Raman spectroscopy, complemented with infrared spectroscopy, was used to study the uranyl carbonate mineral voglite. The mineral has the formula Ca2Cu2+ [(UO2)(CO3)3](CO3)•6H2O, and bands attributed to these vibrating units are readily identified in the Raman spectrum. Symmetric stretching modes at 836 and 1094 cm−1 are assigned to ν1(UO2)2+ and ν1(CO3)2− units, respectively. The ν3 antisymmetric stretching modes of (UO2)2+ are not observed in the Raman spectrum but may be readily observed in the infrared spectrum at 898 cm−1. The ν3 antisymmetric stretching mode of (CO3)2− is observed in the Raman spectrum at 1369 cm−1 as a low intensity band as is also the ν3(CO3)2− infrared modes at 1362, 1425, 1509 and 1566 cm−1. No ν2(CO3)2− Raman bending modes are observed for voglite. The Raman band at 749 cm−1 and the two infrared bands at 747 and 709 cm−1 are assigned to the ν4(CO3)2− bending modes. UO bond and OH…O bond lengths in the structure of voglite were inferred from the infrared and Raman spectra. Copyright © 2007 John Wiley & Sons, Ltd.
Synthesis and Raman spectroscopic characterisation of hydrotalcite with CO32− and (MoO4)2− anions in the interlayer
Authors: Palmer Sara J. , Frost Ray L. , Ayoko Godwin , Nguyen Tai
Published: December 2007

Raman spectroscopy has been used to characterise synthetic mixed carbonate and molybdate hydrotalcites of formula Mg6Al2(OH)16((CO3)2−,(MoO4)2−)·4H2O. The spectra have been used to assess the molecular assembly of the cations and anions in the hydrotalcite structure. The spectra may be conveniently subdivided into spectral features on the basis of the carbonate anion, the molybdate anion, the hydroxyl units and water units. Bands are assigned to the hydroxyl stretching vibrations of water. Three types of carbonate anions are identified: (1) carbonate hydrogen‐bonded to water in the interlayer, (2) carbonate hydrogen‐bonded to the hydrotalcite hydroxyl surface, (3) free carbonate anions. It is proposed that the water is highly structured in the hydrotalcite, as it is hydrogen bonded to both the carbonate and the hydroxyl surface. The spectra have been used to assess the contamination of carbonate in an open reaction vessel in the synthesis of a molybdate hydrotalcite of formula Mg6Al2(OH)16((CO3)2−, (MoO4)2−)·4H2O. Bands are assigned to carbonate and molybdate anions in the Raman spectra. Importantly, the synthesis of hydrotalcites from solutions containing molybdate provides a mechanism for the removal of this oxy‐anion. Copyright © 2007 John Wiley & Sons, Ltd.
Raman spectroscopic characterization of cinnabarin produced by the fungus Pycnoporus sanguineus (Fr.) Murr.
Authors: de Oliveira Luiz F. C. , Le Hyaric Mireille , Berg Marcela M. , de Almeida Mauro V. , Edwards Howell G. M.
Published: December 2007

Raman spectroscopy with 1064 nm laser excitation is used here to identify the chemical composition of the extracts obtained from Pycnoporus sanguineus fungus, in comparison with the data produced from the red fungus itself. Polar and non‐polar solvents were used to separate cinnabarin and ergosterol, respectively, the main components of each extract. The Raman spectra of the extracts are dominated by specific vibrational modes that can be related to these components; in the case of ergosterol the main bands are those assignable to CH stretching and deformation along with bands related to the aryl skeletal rings. The cinnabarin fraction, on the other hand, gives a Raman spectrum where the most important bands are those related to NH2 bending (1510 cm−1) and C quinonoid stretching (1647 cm−1) modes. The Raman spectrum obtained directly from the fungus shows similarity with the cinnabarin fraction, in agreement with the literature information from extracts that cinnabarin is the most significant component present in the red fungus. This result highlights the potential of Raman spectroscopic techniques for the monitoring of the fungus extraction process undertaken in small industries. Copyright © 2007 John Wiley & Sons, Ltd.
Adolescent obsessive compulsive disorder heralding chorea‐acanthocytosis
Authors: Walterfang Mark , Yucel Murat , Walker Ruth , Evans Andrew , Bader Benedikt , Ng Ashley , Danek Adrian , Mocellin Ramon , Velakoulis Dennis
Published: December 2007

We describe one male and one female patient who each developed childhood/adolescent obsessive‐compulsive disorder as a prelude to the development of a typical picture of chorea‐acanthocytosis (ChAc). In each patient, the caudate nucleus showed dramatic atrophy. The role of the caudate in compulsive phenomena, and the predilection for neurological disorders with onset in adolescence to present as major mental illness, is discussed. On the basis of the current evidence and previous findings, we suggest that ChAc can be understood as a disorder whose clinical presentation reflects an interaction between the disease process and the individual's neurodevelopmental stage with both initial interrupted neurodevelopment, and supervening neurodegeneration. © 2007 Movement Disorder Society
4‐Hydroxynonenal: A membrane lipid oxidation product of medicinal interest
Authors: Poli G. , Schaur R.J. , Siems W.G. , Leonarduzzi G.
Published: December 2007

A comprehensive focus on 4‐hydroxynonenal (HNE) as candidate molecule in a variety of pathophysiological conditions occurring in humans is here provided. Despite an active, now well characterized, metabolism in most cells and tissues, HNE can be easily detected and quantified by means of several methods, although with different sensitivity. Measurements of HNE and/or stable metabolites in biological fluids are already applied as lipid peroxidation/oxidative stress markers in a huge number of human disease processes, often sustained by inflammatory reactions. A primary involvement of this aldehydic product of membrane lipid oxidation in inflammation‐related events, as well as in regulation of cell proliferation and growth, in necrotic or apoptotic cell death, appears supported by its marked ability to modulate several major pathways of cell signaling and, consequently, gene expression. The actual knowledge of HNE reactivity, metabolism, signaling and modulatory effect in the various human organs should provide a solid background to the investigation of the aldehyde's contribution to the pathogenesis of human major chronic diseases and would likely promote advanced and oriented applications not only in diagnosis and prevention but also in molecular treatment of human diseases. © 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 4, 569–631, 2008
On optimality of parallel MRI reconstruction in k‐space
Authors: Samsonov Alexey A.
Published: December 2007

Parallel MRI reconstruction in k‐space has several advantages, such as tolerance to calibration data errors and efficient non‐Cartesian data processing. These benefits largely accrue from the approximation that a given unsampled k‐space datum can be synthesized from only a few local samples. In this study, several aspects of parallel MRI reconstruction in k‐space are studied: the design of optimized reconstruction kernels, the effect of regularization on image error, and the accuracy of different k‐space–based parallel MRI methods. Reconstruction of parallel MRI data in k‐space is posed as the problem of approximating the pseudoinverse with a sparse matrix. The error of the approximation is used as an optimization criterion to find reconstruction kernels optimized for the given coil setup. An efficient algorithm for automatic selection of reconstruction kernels is described. Additionally, a total error metric is introduced for validation of the reconstruction kernel and choice of regularization parameters. The new methods yield reduced reconstruction and noise errors in both simulated and real data studies when compared with existing methods. The new methods may be useful for reduction of image errors, faster data processing, and validation of parallel MRI reconstruction design for a given coil system and k‐space trajectory. Magn Reson Med, 2007. © 2007 Wiley‐Liss, Inc.
Atypical facet of Möbius syndrome: Association with facioscapulohumeral muscular dystrophy
Authors: Kolski Hanna K. , Leonard Norma J. , Lemmers Richard J.L.F. , Bamforth John S.
Published: December 2007

We describe a patient with facioscapulohumeral muscular dystrophy (FSHD) associated with Möbius syndrome and congenital ophthalmoplegia. This 7‐year‐old girl had profound limitation of extraocular movements since birth, congenital facial diplegia, neonatal hypotonia, and progressive limb‐girdle weakness. FSHD genetic testing revealed a pathogenic haplotype with a D4Z4 repeat of 30 kb. The father carries the same allele, although is minimally affected. This unusual case expands the genotypic–phenotypic spectrum of FSHD. Muscle Nerve, 2007