bluuebunny/crossref_metadata_2025 huggingface dataset:
Formation of stable nanoparticles via electrostatic complexation between sodium caseinate and gum arabic
Authors: Ye Aiqian , Flanagan John , Singh Harjinder
Published: February 2006

The formation of electrostatic complexes between sodium caseinate and gum arabic (GA) was studied as a function of pH (2.0–7.0), using slow acidification in situ with glucono‐δ‐lactone (GDL) or titration with HCl. The colloidal behavior of the complexes under specific conditions was investigated using absorbance measurements (at 515 or 810 nm) and dynamic light scattering (DLS). In contrast to the sudden increase in absorbance and subsequent precipitation of sodium caseinate solutions at pH < 5.4, the absorbance values of mixtures of sodium caseinate and GA increased to a level that was dependent on GA concentration at pH 5.4 (pHc). The absorbance values remained constant with further decreases in pH until a sudden increase in absorbance was observed (at pH∅︁1). The pH∅︁1 was also dependent upon the GA concentration. Dynamic light scattering (DLS) data showed that the sizes of the particles formed by the complexation of sodium caseinate and GA between pHc and pH∅︁1 were between 100 and 150 nm and these nanoparticles were visualized using negative staining transmission electron microscopy (TEM). Below pH∅︁1, the nanoparticles associated to form larger particles, causing phase separation. ζ‐Potential measurements of the nanoparticles and chemical analysis after phase separation showed that phase separation was a consequence of charge neutralization. The formation of complexes between sodium caseinate and GA was inhibited at high ionic strength (>50 mM NaCl). It is postulated that the structure of the nanoparticles comprises an aggregated caseinate core, protected from further aggregation by steric repulsion of one, or more, electrostatically attached GA molecules. © 2006 Wiley Periodicals, Inc. Biopolymers 82: 121–133, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Structure and pH sensitivity of the transmembrane segment 3 of rhodopsin
Authors: Madathil Sineej , Furlinski Georgi , Fahmy Karim
Published: February 2006

Activation of G protein–coupled receptors (GPCRs) originates in ligand‐induced protein conformational changes that are transmitted to the cytosolic receptor surface. In the photoreceptor rhodopsin, and possibly other rhodopsin‐like GPCRs, protonation of a carboxylic acid in the conserved E(D)RY motif at the cytosolic end of transmembrane helix 3 (TM3) is coupled to receptor activation. Here, we have investigated the structure of synthetic peptides derived from rhodopsin TM3. Polarized FTIR spectroscopy reveals a helical structure of a 31‐mer TM3 peptide reconstituted into PC vesicles with a large tilt of 40–50° of the helical axis relative to the membrane normal. Helical structure is also observed for the TM3 peptide in detergent micelles and depends on pH, especially in the C‐terminal sequence. In addition, the fluorescence emission of the single tyrosine of the D(E)RY motif in the TM3 peptide exhibits a pronounced pH sensitivity that is abolished when Glu is replaced by Gln, demonstrating that protonation of the conserved Glu side chain affects the structure in the environment of the D(E)RY motif of TM3. The pH regulation of the C‐terminal TM3 structure may be an intrinsic feature of the E(D)RY motif in other class I receptors, allowing the coupling of protonation and conformation of membrane‐exposed residues in full‐length GPCRs. © 2006 Wiley Periodicals, Inc. Biopolymers 82:329–333, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Enzymatic hydrolysis of polysaccharide‐rich particulate organic waste
Authors: He Pin‐Jing , Lü Fan , Shao Li‐Ming , Pan Xiu‐Jiang , Lee Duu‐Jong
Published: January 2006

Hydrolysis of organic particulates in rapid fermentative processes can be inhibited. The volatile fatty acids (VFA) released during fermentation reduce pH. Whether VFA or the drop in pH inhibits hydrolysis is unclear. The effects of pH and acetate on the enzymatic hydrolysis of a potato sample that contains both carbohydrate and protein were studied at fixed pH (5–9) in the presence/absence of 20 g/L of acetate. Experimental results showed that the effects of pH and acetate on the hydrolysis of carbohydrate differed from those on the hydrolysis of protein. Numerous kinetic models fitted the hydrolysis data obtained during the first 40 h of hydrolysis when inhibitory effects were insignificant. The Chen‐Hashimoto model was used herein to fit the hydrolysis data obtained during 144 h of reaction. Also, the non‐competitive inhibition model of three inhibitors (H+, OH−, total/undissociated/dissociated acetate) successfully described the inhibition of the hydrolysis of both carbohydrate and protein. © 2006 Wiley Periodicals, Inc.
Lipid peroxidation and total antioxidant status in patients with breast cancer
Authors: Erten Şener Derya , Gönenç Aymelek , Akıncı Melih , Torun Meral
Published: January 2006

Oxidative stress is considered to be involved in the pathophysiology of all cancers. The aim of this study is to examine oxidative stress and antioxidant status in patients with breast cancer by evaluation of the serum levels of total antioxidant capacity (TAC) and lipid peroxidation products as malondialdehyde (MDA) and lipid hydroperoxide and to investigate the relationship between these parameters, oxidative stress and serum lipids and lipoproteins. In our study, serum TAC, MDA, lipid hydroperoxide, HDL‐cholesterol, VLDL‐cholesterol, LDL‐cholesterol, total cholesterol, triacylglycerol (TAG), albumin and uric acid levels of 56‐breast cancer patients in different clinical stages and 18 healthy women were determined. Significantly lower‐levels of TAC were detected in patients with breast cancer in comparison to controls (2.01 ± 0.01 mmol/l and 2.07 ± 0.03 mmol/l, respectively, p < 0.05). Serum MDA levels of the patients were higher compared to the controls (3.64 ± 0.25 µM and 2.72 ± 0.22 µM, respectively, p < 0.05). No significant difference between lipid hydroperoxide levels of patients and controls was found (0.33 ± 0.05 µM and 0.32 ± 0.01 µM, respectively, p > 0.05). These data show that lower TAC and higher MDA levels i.e. increased oxidative stress may be related to breast cancer. Copyright © 2006 John Wiley & Sons, Ltd.
Protective effect of cerebrocrast on rat brain ischaemia induced by occlusion of both common carotid arteries
Authors: Brīede Janïna , Duburs Gunárs
Published: January 2006

Diabetes mellitus is accompanied by several cardiovascular complications including atherosclerosis, cerebral ischaemia and stroke. We examined the neuroprotective effect of a 1,4‐dihydropyridine derivative cerebrocrast (C, a new antidiabetic agent, synthesized in the Latvian Institute of Organic Synthesis) on the level of ATP in the brain, and on changes of the EEG and ECG, as well as blood pressure parameters in anaesthetized Wistar male rats before and during 10‐min occlusion of both common carotid arteries. Cerebrocrast was administered i.v. at doses of 1.0 and 10 µg/kg in the v. femoralis 20 min prior to ischaemia. After 10‐min ischaemia animals were decapitated and the brain was immediately frozen in liquid nitrogen and subsequently used for analysis of changes of ATP contention.

Cerebrocrast, administered at doses of 1.0 and 10 µg/kg 20 min prior to occlusion of both common carotid arteries, completely prevented a fall in the ATP content of brain compared with the control rats. In control rats the content of ATP in brain during ischaemia decreased from 2.77 ± 0.22 (basal level) to 1.74 ± 0.20 µmol/g as a result of ischaemia. By administration of cerebrocrast 20 min before occlusion of the arteries, the content of ATP in the brain remained at the level of preischaemia (1.0 µg/kg C + ischaemia 2.82 ± 0.36; 10 µg/kg C + ischaemia 2.42 ± 0.22 µmol/g). Analysis of EEG parameters both before and during 10 min of occlusion showed that at a C dose of 1.0 µg/kg before occlusion produced a regular alpha rhythm during ischaemia and prevented cerebral bioelectric activity from significant changes. The depression of basal rhythm was observed at a C dose of 10 µg/kg during ischaemia in two rats out of six as well as an increase in the ECG ST segment above the isoelectric line. Blood pressure was decreased by about 10–20 mm Hg.

We propose that pretreatment of rats with cerebrocrast at doses of 1.0 or 10 µg/kg 20 min prior to ischaemia can prevent ischaemic damage of rat brain, maintain necessary energy consumption, promote ATP production in brain cells, and prevent significant changes in EEG and ECG parameters. These properties are important in diabetes mellitus and its evoked cardiovascular complications as stroke, ischaemia, etc. Copyright © 2006 John Wiley & Sons, Ltd.
The α‐to‐β Conformational Transition of Alzheimer's Aβ‐(1–42) Peptide in Aqueous Media is Reversible: A Step by Step Conformational Analysis Suggests the Location of β Conformation Seeding
Authors: Tomaselli Simona , Esposito Veronica , Vangone Paolo , van Nuland Nico A. J. , Bonvin Alexandre M. J. J. , Guerrini Remo , Tancredi Teodorico , Temussi Piero A. , Picone Delia
Published: January 2006

Current views of the role of β‐amyloid (Aβ) peptide fibrils range from regarding them as the cause of Alzheimer's pathology to having a protective function. In the last few years, it has also been suggested that soluble oligomers might be the most important toxic species. In all cases, the study of the conformational properties of Aβ peptides in soluble form constitutes a basic approach to the design of molecules with “antiamyloid” activity. We have experimentally investigated the conformational path that can lead the Aβ‐(1–42) peptide from the native state, which is represented by an α helix embedded in the membrane, to the final state in the amyloid fibrils, which is characterized by β‐sheet structures. The conformational steps were monitored by using CD and NMR spectroscopy in media of varying polarities. This was achieved by changing the composition of water and hexafluoroisopropanol (HFIP). In the presence of HFIP, β conformations can be observed in solutions that have very high water content (up to 99 % water; v/v). These can be turned back to α helices simply by adding the appropriate amount of HFIP. The transition of Aβ‐(1–42) from α to β conformations occurs when the amount of water is higher than 80 % (v/v). The NMR structure solved in HFIP/H2O with high water content showed that, on going from very apolar to polar environments, the long N‐terminal helix is essentially retained, whereas the shorter C‐terminal helix is lost. The complete conformational path was investigated in detail with the aid of molecular‐dynamics simulations in explicit solvent, which led to the localization of residues that might seed β conformations. The structures obtained might help to find regions that are more affected by environmental conditions in vivo. This could in turn aid the design of molecules able to inhibit fibril deposition or revert oligomerization processes.
A CD14 Domain with Lipopolysaccharide‐Binding and ‐Neutralizing Activity
Authors: Voss Söhnke , Welte Stefan , Fotin‐Mleczek Mariola , Fischer Rainer , Ulmer Artur J. , Jung Günther , Wiesmüller Karl‐Heinz , Brock Roland
Published: January 2006

The interaction of lipopolysaccharide with CD14 plays a key role in signaling that activates an early defense against pathogens but also contributes to the development of sepsis and septic shock. Here we have mapped the entire 356‐amino‐acid protein with synthetic 20‐amino‐acid peptides and have identified a new lipopolysaccharide‐binding domain with a strong LPS‐neutralizing activity. Moreover, analysis of the structure–activity relationship of this peptide, which corresponds to amino acids 81–100 of human CD14, revealed that leucines 87, 91, and 94 are essential for these activities. The functional relevance of these residues was confirmed by cellular expression of mutant CD14 proteins that are no longer able to bind LPS. Furthermore, the peptide provided a basis for the generation of highly soluble analogues with stronger lipopolysaccharide‐neutralizing activity.
Determination of Operating Conditions for Controlled Batch Cooling Crystallization
Authors: Yang G. , Louhi‐Kultanen M. , Sha Z. , Kallas J.
Published: January 2006

In batch cooling crystallization, the supersaturation courses, obtained at different operating conditions, directly influence the crystallization kinetics. Therefore, the product sizes obtained strongly depend on the operating conditions. In order to control the supersaturation level during batch processes, a cooling model was introduced which included the seeding conditions, cooling rate, batch time, and crystallization kinetics. The cooling profiles, which maintain the different constant levels of supersaturation, were, therefore, predicted by numerically solving the model equation. Furthermore, the mean product sizes, obtained with the different specified cooling profiles, were simulated using the mass balance and the moment transformation of the population balance. Based on the simulation results, the relationship between the operating conditions, the supersaturation level, and product size was established. Hence, a strategy to select the appropriate operating conditions, in order to meet the required mean product size, was demonstrated. The results highlight that, by using the developed strategy, the batch cooling crystallization can be operated at optimal conditions, e.g., short batch time, slow cooling rate, or low seed loading. A potassium dihydrogen phosphate (KDP) system was selected for the case study.
Raman Spectroscopy – A Powerful Tool for the Quantitative Determination of the Composition of Polymorph Mixtures: Application to CaCO3 Polymorph Mixtures
Authors: Dandeu A. , Humbert B. , Carteret C. , Muhr H. , Plasari E. , Bossoutrot J. M.
Published: January 2006

Raman spectroscopy is an ideal method for identifying polymorphs, because it provides excellent fingerprint spectra specific to each crystal structure. Currently, Raman spectroscopy is successfully used for the quantitative polymorphic analysis of calcium carbonate only in the case of binary mixtures. When a third polymorph is present in the mixture, errors in the quantitative determination increase due to the difficulty in discriminating the different phases in the Raman spectra. In the present work, a new method is developed for mixtures containing more than two polymorphs and tested in the case of vaterite, aragonite, and calcite mixtures of different compositions. It is proved that Raman spectroscopy is a powerful, accurate, and reliable technique for quantitative determination of polymorph mixtures of calcium carbonate. The method can be used for other compounds exhibiting multiple polymorphs.
Utilization of Focused Beam Reflectance Measurement in the Control of Crystal Size Distribution in a Batch Cooled Crystallizer
Authors: Barthe S. , Rousseau R. W.
Published: January 2006

Controlling crystal size distribution (CSD) is important to downstream processing and to product quality. The distribution can be characterized by a mean or dominant size and the spread about the mean or dominant size. The development of tools leading to the control of the distribution in a batch crystallizer is the main topic of the present study. An experimentally based control scheme was implemented for batch cooling crystallization of paracetamol from ethanol solutions. Estimates of the CSD in the batch crystallizer were obtained by applying a model of the octahedral paracetamol crystals to a chord length distribution (CLD) obtained from focused beam reflectance measurement (FBRM) and Lasentec software. The model estimates showed reasonably good agreement with results obtained from sieve analyses performed at the end of the runs.
Factors Affecting Metal Removal in Mixed Sulfide Precipitation
Authors: Lewis A. , Swartbooi A.
Published: January 2006

Sulfide precipitation of nickel and cobalt was investigated in three reactors: batch, seeded fluidized bed with an aqueous sulfide source, and bubble column with a gaseous sulfide source. In terms of metal removal and settling rate, the sulfide system is more efficient than either hydroxide or carbonate. In the batch system, the kinetics of the nickel and cobalt sulfide precipitation reactions are first order in metal and sulfide concentrations. Metal removals of approximately 90 % were achieved, but when excess sulfide was used the removals decreased, probably due to the formation of aqueous polysulfide species. In the fluidized bed, significant fines were measured, due to homogeneous nucleation and attrition. It was concluded that this reactor configuration is not suitable for these very high supersaturation levels. Using a gaseous sulfide source reduced the supersaturation and the measured metal removal improved.
Validation of a Model for Multiple Agglomeration
Authors: Cameirão A. , Espitalier F. , David R. , Rouleau L.
Published: January 2006

A two‐step agglomeration model is developed for the crystallization of a zeolite. It accounts for the crystallization of crystallites from the amorphous phase and the subsequent growth and agglomeration processes. The model explains the morphology of agglomerates with multiple structures, which were obtained. When porosity of the secondary agglomerates is introduced in the model, the agreement with experimental data is largely improved.
Precipitation of L‐Glutamic Acid: Determination of Nucleation Kinetics
Authors: Schöll J. , Vicum L. , Müller M. , Mazzotti M.
Published: January 2006

This work presents a new procedure to determine the nucleation kinetics during the reactive precipitation of an organic substance. The new method has been applied to the pH‐shift precipitation of L‐glutamic acid upon mixing of an aqueous monosodium glutamate solution with hydrochloric acid. The induction time has been measured precisely in a stirred batch reactor by the combination of two in‐situ measurement techniques, namely ATR‐FTIR spectroscopy (attenuated total reflection Fourier Transform technique) and Focused Beam Reflectance Measurement (FBRM). It is shown that ATR‐FTIR is a suitable tool to measure the concentrations of the different L‐glutamic acid ions, and can be used to determine the starting time of the process when the desired supersaturation is established in the reactor. The onset of particle formation is detected through FBRM. The precipitated polymorph is identified using in‐situ Raman spectroscopy and Particle Vision & Measurement (PVM). Finally, the induction time is used together with the independently measured growth kinetics to determine the nucleation rate.
Factors Affecting the Polymorphic Outcome of Glycine Crystals Constrained on Patterned Substrates
Authors: Lee A. Y. , Lee I. S. , Myerson A. S.
Published: January 2006

The primary goal of crystallization process is to generate particles with controlled size, shape and solid form, and the desired chemical purity. Many different types of approaches including molecular level strategies have been devised and employed to control the final structure of crystals. One promising approach is the utilization of self‐assembled monolayers (SAMs) as templates. Recently, we reported that single glycine crystals can nucleate on patterned metallic square islands, with the size and morphology of the particles controlled by the dimensions of the islands or the concentration of the solution. Herein, the effect of the solution concentration on the polymorphic outcome of glycine crystals confined to hydrophilic metallic islands is investigated. Furthermore, we examine how variations in the solvent evaporation rate can impact the polymorph distribution of glycine.
Purification of Phosphoric Acid from Waste Acid Etchant using Layer Melt Crystallization
Authors: Kim K.‐J.
Published: January 2006

Spent acid etchant is the corrosive waste coming from the etching process of semiconductor manufacturing plants. This waste solution consists of phosphoric acid, nitric acid and acetic acid, and includes various toxic metallic impurities. In this work, the recovery of phosphoric acid from the waste etchant was conducted by removal of metallic impurities, nitric acid, and acetic acid, using static melt crystallization. The effect of cooling rate, amount of seeds, subcooling, and sweating on the distribution coefficient was investigated. Nitric acid and acetic acid were successfully removed by single‐stage layer crystallization. The quantity of metallic impurities of the purified phosphoric acid was 1/1000 times smaller than that of the crude etchant.
Investigation of Precipitation of Calcium Carbonate at High Supersaturations
Authors: Schlomach J. , Quarch K. , Kind M.
Published: January 2006

The formation mechanism of precipitated calcium carbonate from aqueous solution under industrial conditions (high supersaturation) was investigated in a semi‐batch and in a continuous mixing nozzle process. The influence of potassium hydroxide and magnesium chloride on crystal modification and particle size were investigated in both processes. Rheological properties of the magnesium stabilized amorphous gel structure have been measured. A similarity between the formation process of calcium carbonate and precipitated silica has been proven.
Synthesis and Pharmacological Evaluation of 8‐ and 9‐Substituted Benzolactam‐V8 Derivatives as Potent Ligands for Protein Kinase C, a Therapeutic Target for Alzheimer's Disease
Authors: Mach Ulrich R. , Lewin Nancy E. , Blumberg Peter M. , Kozikowski Alan P.
Published: January 2006

A central element in the pathophysiology of Alzheimer's disease (AD) is the formation of amyloid plaques, which result from abnormal processing of the amyloid precursor protein (APP). The processing of APP is largely provided by three key enzymes, namely the α‐, β‐, and γ‐secretases. As the latter two contribute to the formation of neurotoxic Aβ fragments while α‐secretase does not, a decrease in the amyloidogenic products can be brought about either by inhibition of the β‐ and γ‐secretases or through the activation of α‐secretase. It is now known that the activation of protein kinase C (PKC) enhances α‐secretase activity and therefore represents a possible target for the development of agents urgently needed for the treatment of this devastating neurodegenerative disorder. In the present study, new benzolactam‐V8‐based PKC activators were synthesized and tested for their binding affinity toward PKCα. All compounds tested showed binding values in the nanomolar concentration range. In accordance with previous publications, 9‐substitution dramatically increased PKC binding affinity in comparison with the corresponding 8‐substituted analogues. In addition to the location of the side chain on the aromatic ring, the binding affinities of these benzolactams were found to depend on the orientation, length, and electronic properties of this appendage. An interesting decrease in binding affinity was found for the 9‐thienyl analogue 13, suggesting adverse electronic interactions of the sulfur atom with PKC or parts of the cellular membrane.
Plasma Edge Physics with B2‐Eirene
Authors: Schneider R. , Bonnin X. , Borrass K. , Coster D. P. , Kastelewicz H. , Reiter D. , Rozhansky V. A. , Braams B. J.
Published: January 2006

The B2‐Eirene code package was developed to give better insight into the physics in the scrape‐off layer (SOL), which is defined as the region of open field‐lines intersecting walls. The SOL is characterised by the competition of parallel and perpendicular transport defining by this a 2D system. The description of the plasma‐wall interaction due to the existence of walls and atomic processes are necessary ingredients for an understanding of the scrape‐off layer. This paper concentrates on understanding the basic physics by combining the results of the code with experiments and analytical models or estimates. This work will mainly focus on divertor tokamaks, but most of the arguments and principles can be easily adapted also to other concepts like island divertors in stellarators or limiter devices.

The paper presents the basic equations for the plasma transport and the basic models for the neutral transport. This defines the basic ingredients for the SOLPS (Scrape‐Off Layer Plasma Simulator) code package. A first level of understanding is approached for pure hydrogenic plasmas based both on simple models and simulations with B2‐Eirene neglecting drifts and currents. The influence of neutral transport on the different operation regimes is here the main topic. This will finish with time‐dependent phenomena for the pure plasma, so‐called Edge Localised Modes (ELMs). Then, the influence of impurities on the SOL plasma is discussed. For the understanding of impurity physics in the SOL one needs a rather complex combination of different aspects. The impurity production process has to be understood, then the effects of impurities in terms of radiation losses have to be included and finally impurity transport is necessary. This will be introduced with rising complexity starting with simple estimates, analysing then the detailed parallel force balance and the flow pattern of impurities. Using this, impurity compression and radiation instabilities will be studied. This part ends, combining all the elements introduced before, with specific, detailed results from different machines. Then, the effect of drifts and currents is introduced and their consequences presented. Finally, some work on deriving scaling laws for the anomalous turbulent transport based on automatic edge transport code fitting procedures will be described. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Effects of sulfonylureas on mitochondrial ATP‐sensitive K+channels in cardiac myocytes: implications for sulfonylurea controversy
Authors: Sato Toshiaki , Nishida Hirofumi , Miyazaki Masaru , Nakaya Haruaki
Published: January 2006

Background

Mitochondrial ATP‐sensitive K+(mitoKATP) channel plays a key role in cardioprotection. Hence, a sulfonylurea that does not block mitoKATPchannels would be desirable to avoid damage to the heart. Accordingly, we examined the effects of sulfonylureas on the mitoKATPchannel and mitochondrial Ca2+overload.

Methods

Flavoprotein fluorescence in rabbit ventricular myocytes was measured to assay mitoKATPchannel activity. The mitochondrial Ca2+concentration was measured by loading cells with rhod‐2.

Results

The mitoKATPchannel opener diazoxide (100 µM) reversibly increased flavoprotein oxidation to 31.8 ± 4.3% (n= 5) of the maximum value induced by 2,4‐dinitrophenol. Glimepiride (10 µM) alone did not oxidize the flavoprotein, and the oxidative effect of diazoxide was unaffected by glimepiride (35.4 ± 3.2%,n= 5). Similarly, the diazoxide‐induced flavoprotein oxidation was unaffected both by gliclazide (10 µM) and by tolbutamide (100 µM). Exposure to ouabain (1 mM) for 30 min produced mitochondrial Ca2+overload, and the intensity of rhod‐2 fluorescence increased to 197.4 ± 7.2% of baseline (n= 11). Treatment with diazoxide significantly reduced the ouabain‐induced mitochondrial Ca2+overload (149.6 ± 5.1%,n= 11,p< 0.05versusouabain alone), and the effect was antagonized by the mitoKATPchannel blocker 5‐hydroxydecanoate (189.8 ± 27.8%,n= 5) and glibenclamide (193.1 ± 7.7%,n= 8). On the contrary, cardioprotective effect of diazoxide was not abolished by glimepiride (141.8 ± 7.8%,n= 6), gliclazide (139.0 ± 9.4%,n= 5), and tolbutamide (141.1 ± 4.5%,n= 7).

Conclusions

Our results indicate that glimepiride, gliclazide, and tolbutamide have no effect on mitoKATPchannel, and do not abolish the cardioprotective effects of diazoxide. Therefore, these sulfonylureas, unlike glibenclamide, do not interfere with the cellular pathways that confer cardioprotection. Copyright © 2006 John Wiley & Sons, Ltd.
The Epoxy‐Ramberg–Bäcklund Reaction (ERBR): A Sulfone‐Based Method for the Synthesis of Allylic Alcohols
Authors: Evans Paul , Johnson Paul , Taylor Richard J. K.
Published: January 2006

The epoxy‐Ramberg–Bäcklund reaction (ERBR) is outlined, in which α,β‐epoxy sulfones are converted into a range of mono‐, di‐ and tri‐substituted allylic alcohols, on treatment with base. Modification of this method enabled the preparation of enantio‐enriched allylic alcohols following the diastereoselective epoxidation of enantio‐enriched vinyl sulfones that were accessed efficiently from the chiral pool. The scope, optimisation and limitations of the ERBR as a method for the preparation of allylic alcohols are discussed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Palladium‐ and Copper‐Mediated Direct C‐2 Arylation of Azoles — Including Free (NH)‐Imidazole, ‐Benzimidazole and ‐Indole — Under Base‐Free and Ligandless Conditions
Authors: Bellina Fabio , Cauteruccio Silvia , Rossi Renzo
Published: January 2006

The first palladium‐ and copper‐mediated C‐2 arylations of thiazole, oxazole, N‐methylimidazole and N‐arylimidazoles, as well as of free (NH)‐imidazole, ‐benzimidazole and ‐indole, with aryl iodides under ligandless and base‐free conditions are described. Complete selectivity has been achieved under these unprecedented conditions, which allow the use of substrates containing base‐sensitive groups, such the NH groups of imidazole, benzimidazole or indole, without their prior protection. No N‐arylation products were detected in the arylation of free (NH)‐imidazole, ‐benzimidazole and ‐indole. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Gold Catalysis: Evidence for the In‐situ Reduction of Gold(III) During the Cyclization of Allenyl Carbinols
Authors: Hashmi A. Stephen K. , Blanco M. Carmen , Fischer Dirk , Bats Jan W.
Published: January 2006

Products of an oxidative coupling were obtained in the gold(III)‐catalyzed cycloisomerization of tertiary allenyl carbinols. The absence of reduced organic products and an increase of these coupling products with the amount of gold(III) catalyst suggests that gold(III) is reduced in situ, possibly to gold(I) catalysts which were also shown to be active for these transformations. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Prefrontal modulation of working memory performance in brain injury and disease
Authors: Hillary Frank G. , Genova Helen M. , Chiaravalloti Nancy D. , Rypma Bart , DeLuca John
Published: January 2006

The inter‐related cognitive constructs of working memory (WM) and processing speed are fundamental components to general intellectual functioning in humans. Importantly, both WM and processing speed are highly susceptible to disruption in cases of brain injury, neurologic illness, and even in normal aging. A goal of this article is to summarize and critique the functional imaging studies of speeded working memory in neurologically impaired populations. This review focuses specifically on the role of the lateral prefrontal cortex in mediating WM performance and integrates the relevant WM literature in healthy adults with the current findings in the clinical literature. One important finding emerging from a summary of this literature is the dissociable contributions made by ventrolateral and dorsolateral prefrontal cortex (VLPFC and DLPFC) in guiding performance on tasks of WM. Throughout this review, it is shown that when cerebral resources are challenged, it is DLPFC, and often right DLPFC specifically, that plays a critical role in modulating WM functioning. In addition, this article will examine the relationship between task performance and brain activation across studies to clarify the role of increased DLPFC activity in clinical samples. Finally, explanations are offered for the observed increased DLPFC activation and the potentially unique role of right DLPFC in mediating WM performance during periods of cerebral challenge. Hum. Brain Mapp, 2006. © 2006 Wiley‐Liss, Inc.
Syntheses of some new 1H‐pyrazole, pyridazin‐3(2H)‐one, and oxazin‐4‐one derivatives
Authors: Akbaş Esvet , Aslanoǧlu Furgan
Published: January 2006

The new 1H‐pyrazole‐3‐carboxylic acid 2, pyridazin‐3(2H)‐one 3, and their various derivatives were prepared by the reactions of the 4‐benzoyl‐5‐phenyl‐2,3‐dihydro‐2,3‐furandione 1 and 2,5‐dichlorophenylhydrazine. Pyrazolo[3,4‐d]pyridazine 7 was obtained from cyclization of the pyrazole‐3‐carboxylic acid 2 with 2,5‐dichlorophenylhydrazine. The reaction of 1 and pyrazole‐3‐carbonitriles 6 gave the new oxazin‐4‐one 9 derivatives. The structures of compounds were characterized on the basis of elemental analyses, mass, IR, 1H, and 13C NMR spectra. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:8–12, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20170
Diastereoselective cycloalkylation of phosphoryl and thiophosphoryl acetonitriles by α,ψ‐dihalogenalkanes under phase transfer catalysis conditions
Authors: Odinets I. L. , Vinogradova N. M. , Lyssenko K. A. , Petrovskii P. V. , Mastryukova T. A. , Röschenthaler G‐V.
Published: January 2006

Cycloalkylation of phosphoryl and thiophosphoryl acetonitriles 2 by α,ψ‐dihalogenalkanes was found to proceed diastereoselectively under phase transfer catalytic conditions yielding 1‐(phosphoryl)‐2‐methyl‐cycloalkane carbonitriles as trans‐isomers with identical configuration of asymmetric cyclic carbon atoms (RC* RC*). In the case of additional asymmetric phosphorus atom in the starting substrate, trans‐isomers are formed as a mixture of diastereomers differing in the configuration of the phosphorus atom (SP* RC* RC* and RP* RC* RC*). © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:13–21, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20186
The iodine atom transfer addition reaction (I‐ATRA) initiated by AIBN: Optimization, scope and radical reaction pathways
Authors: Bałczewski Piotr , Szadowiak Aldona , Białas Tomasz
Published: January 2006

Optimization of reaction conditions (alkene, halide, solvent, stoichiometry, manners of the reagents addition, and reaction time) of the I‐ATRA reactions involving 1‐iodoalkylphosphonates was carried out. GC–MS–CI/EI analyses showed main and side products of this reaction and the corresponding radical reaction pathways leading to products derived from phosphorus and nonphosphorus containing iodides, as well as explained the source of hydrogen in radical reduction processes accompanying the I‐ATRA reaction. Synthesis of some 3‐iodoalkyl and 3‐iodoalkenylphosphonates was also presented based on the optimized procedure. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:22–35, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20187
Complexes of esters of ethylenediphosphonic acid with lanthanide nitrates—synthesis and structure
Authors: Haupt Erhard T. K. , Kopf Jürgen , Petrova Jordanka , Arabadzhiev Vladislav , Momchilova Snezhana
Published: January 2006

The lanthanide complexes L2Ln(NO3)3 (3) and L′ 3[Ln(NO3)3]2 (5) (Stewart and Siddall III. J Inorg Nucl Chem 1971, 33, 2965–2970) were obtained, where L is the tetraethyl ester of ethylenediphosphonic acid (2), L′ is the tetraisopropyl ester of ethylenediphosphonic acid (4), and Ln is La, Ce, Sm, Eu, and Er. In extension of a former study, they were characterized additionally with NMR spectroscopy. In contrast to the compounds of type 3, the erbium complex of the ligand L is consistent with the formula L3[Er(NO3)3]2. The crystal structure of the complex 3a (Ln = La) is determined by single crystal X‐ray diffraction. The complex is found to crystallize in the monoclinic space group C2/c with a = 15.1415(4) Å, b = 14.9749(4) Å, c = 18.3887(5) Å, β = 114.129(1)ˆ, T = 153 K, V = 3805.2(2) Å3, Z = 4, ρcalc = 1.622 g/cm3, R1 = 0.023, R2w = 0.058, S = 1.08 for all 6823 reflections. The complex 3a consists of polymer chains with bridged bidentate phosphonate ligands. The lanthanum atom is coordinated by ten oxygen atoms, six of them from the three bidentate nitrate ions, and four from the two phosphonate ligands. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:36–46, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20188
Therapy of Hepatitis B — Viral Suppression or Eradication?
Authors: Perrillo Robert P.
Published: January 2006

The practicing clinician is currently faced with a number of treatment options for chronic hepatitis B. Beginning in 1998 with the licensing of lamivudine and subsequently adefovir, the treatment paradigm shifted from 4 to 6 months of conventional alfa interferon to a year of nucleoside analog therapy. However, prolonged treatment with nucleoside analogs is often needed to optimize virological response. Recently, a 48-week regimen of pegylated interferon for hepatitis B e antigen (HBeAg)-positive and HBeAg-negative chronic hepatitis B has been shown to be effective, and long-term nucleoside analog therapy has been demonstrated to maintain viral suppression. These findings have added to the complexity of decision-making and have raised questions about whether a finite course of pegylated interferon or nucleoside analog therapy, with possible long-term maintenance, is better as first-line therapy. Each of these fundamentally different approaches has advantages and limitations, and both have a place in the therapeutic armamentarium against chronic hepatitis B. Long-term therapy with nucleoside analogs, however, raises a number of practical concerns that have not been fully addressed as of yet. I will present evidence in support of the recommendation that antiviral therapy should ideally be directed toward achieving the highest rate of viral clearance with the shortest interval of treatment.
Therapy of Hepatitis C: From Empiricism to Eradication
Authors: Pawlotsky Jean-Michel
Published: January 2006

The complications of chronic hepatitis C virus infection can be prevented by antiviral therapy. The initial choice of interferon alfa and, subsequently, ribavirin as potential treatments for chronic hepatitis C was empirical. Nevertheless, the combination of pegylated interferon alfa and ribavirin has become the standard treatment of chronic hepatitis C. Since the advent of interferon-based therapy, enormous progress has been made in understanding the mechanisms of treatment efficacy and failure, and in everyday patient management. The principal advances are: a better understanding of hepatitis C virus steady-state kinetics and the antiviral mechanisms of interferon and ribavirin; easier treatment decisions thanks to novel assays to assess liver disease severity and the virological characteristics of infection; a better use of virological tests to tailor therapy; a better management of adverse effects; a better understanding of virological treatment failure; and a better management of “special” populations, including patients with decompensated cirrhosis and end-stage liver disease, liver transplant recipients, hemodialysis patients and renal transplant recipients, human immunodeficiency virus-coinfected patients, intravenous drug users and patients on opiate replacement therapy, or virological non responders to previous therapies. Steady-state HCV kinetics offers several potential targets for new drugs. These targets should ideally be hit simultaneously in order to achieve viral eradication within a reasonable time frame. Future drugs for HCV infection will belong to four main categories, including new interferons, alternatives to ribavirin, specific HCV inhibitors, and immune modulators. New treatments and vaccines might make it possible to eradicate HCV in the future.
Mirtazapine naturalistic depression study (in Sweden)—MINDS(S): clinical efficacy and safety
Authors: Wålinder Jan , Prochazka Jiri , Odén Anders , Sjödin Ingemar , Dahl Marja‐Liisa , Ahlner Johan , Bengtsson Finn
Published: January 2006

Objective

To study how implementation of a naturalistic trial design for mirtazapine treatment in major depressive disorder for six (up to 12) months could be used and evaluated by means of clinical efficacy and safety.

Method

An open‐labelled, prospective, multicenter, non‐comparative trial was conducted during a 2‐year period in patients with major depression according to DSM‐IV treated in psychiatric departments and primary care in Sweden. Minimal inclusion and exclusion criteria were used in order to diminish the potential patient selection bias. Maximum flexibility of the dosage of mirtazapine was allowed, and clinical assessments included MADRS, CGI, vital signs and spontaneous reporting of adverse events.

Results

192 patients were found eligible and enrolled in the study. A significant improvement in depressive symptoms according to MADRS and CGI was observed including particularly marked sleep improvement early in the treatment. Slight increases in body weight and BMI were observed. The investigational drug was well tolerated overall.

Conclusion

The clinical efficacy and safety of mirtazapine found in this naturalistic setting is in line with previously reported data on mirtazapine in traditional controlled clinical trials. The results confirm that the naturalistic study design facilitated conduct of the trial. The authors suggest that this type of study design should also be applied to other antidepressant drugs that are frequently prescribed in the general population. Copyright © 2006 John Wiley & Sons, Ltd.
Physics of polypeptide multilayer films
Authors: Haynie Donald T.
Published: January 2006

Polypeptide multilayer films are promising for the development of coatings for implant devices, biosensors, and artificial cells. This paper discusses aspects of the physics of these films. Three sub‐topics in the physics of peptide adsorption in multilayer film assembly covered here are peptide structure at the film/solid support interface, adsorbed layer thickness, and dynamics of peptide adsorption. A synopsis of work in these areas is preceded by an introduction to the subject and a review of some aspects of polymer theory. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
Mechanical and morphological characterization of homogeneous and bilayered poly(2‐hydroxyethyl methacrylate) scaffolds for use in CNS nerve regeneration
Authors: Carone Terrance W. , Hasenwinkel Julie M.
Published: January 2006

Homogeneous and bilayered macroporous poly(2‐hydroxyethyl methacrylate), p(HEMA), hydrogel scaffolds were examined as possible matrices for nerve regeneration in the CNS. An important issue to consider for a CNS scaffold is that it must be able to closely mimic the natural tissue it is replacing, while remaining intact, and mechanically stable enough to allow for regenerating axons to elongate through it. Phase‐separated homogeneous and bilayered p(HEMA) scaffolds were fabricated, by varying water, crosslinking, and initiating agents; all of which directly affected the mechanical properties of the polymer. An increase in water concentration resulted in a decrease in the modulus for a given crosslinking and initiating concentration for all homogenous scaffolds, but the same result was not evident in the bilayered scaffolds. The distinct regions within the bilayered scaffolds generate a matrix, containing both a highly porous region with modulus values representative of spinal cord tissue, as well as a nonporous region that provides overall mechanical stability to the entire implant. The overall result is a composite matrix for possible use in CNS nerve regeneration, which mimics the mechanical properties of spinal tissue, but can withstand the forces that it will be subjected to in the injury site. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006
TP53 and p16INK4A, but not H‐KI‐Ras, are involved in tumorigenesis and progression of pleomorphic adenomas
Authors: Augello Claudia , Gregorio Valter , Bazan Viviana , Cammareri Patrizia , Agnese Valentina , Cascio Sandra , Corsale Simona , Calò Valentina , Gullo Arianna , Passantino Rita , Gargano Grazia , Bruno Loredana , Rinaldi Gaetana , Morello Vincenza , Gerbino Aldo , Tomasino Rosa Maria , Macaluso Marcella , Surmacz Eva , Russo Antonio
Published: January 2006

The putative role of TP53 and p16INK4A tumor suppressor genes and Ras oncogenes in the development and progression of salivary gland neoplasias was studied in 28 cases of pleomorphic adenomas (PA), 4 cases of cystic adenocarcinomas, and 1 case of carcinoma ex‐PA. Genetic and epigenetic alterations in the above genes were analyzed by Polymerase Chain Reaction/Single Strand Conformational Polymorphism (PCR/SSCP) and sequencing and by Methylation Specific‐PCR (MS‐PCR). Mutations in TP53 were found in 14% (4/28) of PAs and in 60% (3/5) of carcinomas. Mutations in H‐Ras and K‐Ras were identified in 4% (1/28) and 7% (2/28) of PAs, respectively. Only 20% (1/5) of carcinomas screened displayed mutations in K‐Ras. p16INK4A promoter hypermethylation was found in 14% (4/28) of PAs and 100% (5/5) carcinomas. All genetic and epigenetic alterations were detected exclusively in the epithelial and transitional tumor components, and were absent in the mesenchymal parts. Our analysis suggests that TP53 mutations and p16INK4A promoter methylation, but not alterations in the H‐Ras and K‐Ras genes, might be involved in the malignant progression of PA into carcinoma. © 2006 Wiley‐Liss, Inc.
Cerebrospinal fluid tau, Aß, and phosphorylated tau protein for the diagnosis of Alzheimer's disease
Authors: Formichi Patrizia , Battisti Carla , Radi Elena , Federico Antonio
Published: January 2006

The diagnosis of AD is still largely based on exclusion criteria of secondary causes and other forms of dementia with similar clinical pictures, than the diagnostic accuracy of AD is low. Improved methods of early diagnosis are needed, particularly because drugs treatment is more effective in the early stages of the disease. Recent research focused the attention to biochemical diagnostic markers (biomarkers) and according to the proposal of a consensus group on biomarkers, three candidate CSF markers reflecting the pathological AD processes, have recently been identified: total tau protein (t‐tau), amyloid ß(1–42) protein (Aß42), and tau protein phosphorylated at AD‐specific epitopes (p‐tau). Several articles report reduced CSF levels of Aß42 and increased CSF levels of t‐tau and p‐tau in AD; the sensitivity and specificity of these data are able for discrimination of AD patients from controls. However, the specificity for other dementias is low. According to the literature analysis reported in the present review, we can conclude that the combination of the CSF markers and their ratios may significantly increase the specificity and the accuracy of AD diagnosis. © 2006 Wiley‐Liss, Inc.
Human glioblastoma ADF cells express tyrosinase, L‐tyrosine hydroxylase and melanosomes and are sensitive to L‐tyrosine and phenylthiourea
Authors: Bonfigli Antonella , Zarivi Osvaldo , Colafarina Sabrina , Cimini Anna Maria , Ragnelli Anna Maria , Aimola Pierpaolo , Natali Pier Giorgio , Cerù Maria Paola , Amicarelli Fernanda , Miranda Michele
Published: January 2006

Melanocytes and neuroblasts share the property of transforming L‐tyrosine through two distinct metabolic pathways leading to melanogenesis and catecholamine synthesis, respectively. While tyrosinase (TYR) activity has been shown to be expressed by neuroblastoma it remains to be established as to whether also glioblastomas cells are endowed with this property. We have addressed this issue using the human continuous glioblastoma cell line ADF. We demonstrated that these cells possess tyrosinase as well as L‐tyrosine hydroxylase (TH) activity and synthesize melanosomes. Because the two pathways are potentially cyto‐genotoxic due to production of quinones, semiquinones, and reactive oxygen species (ROS), we have also investigated the expression of the peroxisomal proliferators activated receptor α (PPARα) and nuclear factor‐kB (NFkB) transcription factor as well the effect of L‐tyrosine concentration on cell survival. We report that L‐tyrosine down‐regulates PPARα expression in ADF cells but not neuroblastoma and that this aminoacid and phenylthiourea (PTU) induces apoptosis in glioblastoma and neuroblastoma. © 2006 Wiley‐Liss, Inc.