bluuebunny/crossref_metadata_2025 huggingface dataset:
Polyhedral Monocarbaborane Chemistry. Functionality and Isomerism: Reactions of the [6-Ph-nido-6-CB9H11]- Anion with Aminopyridines NC5H4NH2 to Yield Neutral arachno and closo Ten-Vertex Monocarbaborane Derivatives
Authors: Bullen Neil J. , Kennedy John D.
Published: December 2005

Reaction of NC5H4-2-NH2with the [6-Ph-nido-6-CB9H11]-anion (1) in the presence of hydrated FeCl3gives [6-Ph-9-(NC5H4-2-NH2)-arachno-6-CB9H12] (4) and thence [1-Ph-2-(NC5H4-2-NH2)-closo-1-CB9H8] (5), in which the pyridine substituent is on a boron atom α to the cluster carbon atom. This behaviour contrasts to the reactions of organyl-substituted pyridines NC5H4R to yield neutral 9-pyridinearachnospecies [6-Ph-9-(NC5H4R)-arachno-6-CB9H12] and thence neutral 6-pyridineclosospecies [1-Ph-6-(NC5H4R)-closo-1-CB9H8], in which the pyridine substituent is on a boron atom β to the cluster carbon atom. The chlorinated analogue [1-Ph-2-(NC5H4-2-NH2)-4-Cl-closo-1-CB9H7] (7) is also identified as a minor by-product from the reaction system. Reaction of anion1with NC5H4-4-NH2does not proceed further than [6-Ph-9-(NC5H4-4-NH2)-arachno-6-CB9H12] (8). The 2-NH2compounds4,5and7exhibit intramolecular BH-HN dihydrogen bonding, whereas the 4-NH2compound8exhibits an intermolecular BH-HN dihydrogen-bonded network that involves inversion-related pairs of dihydrogen-bonded chains.
Luminescence of a New Ru(II) Polypyridine Complex Controlled by a Redox-Responsive Protonable Anthra[1,10]phenanthrolinequinone
Authors: Hartl František , Vernier Sandrine , Belser Peter
Published: December 2005

Redox-controlled luminescence quenching is presented for a new Ru(II)-bipyridine complex [Ru(bpy)2(1)]2+ where ligand 1 is an anthra[1,10]phenanthrolinequinone. The complex emits from a short-lived metal-to-ligand charge transfer, 3MLCT state (τ = 5.5 ns in deaerated acetonitrile) with a low luminescence quantum yield (5 × 10-4). The emission intensity becomes significantly enhanced when the switchable anthraquinone unit is reduced to corresponding hydroquinone. On the contrary, chemical one-electron reduction of the anthraquinone moiety to semiquinone in aprotic tetrahydrofuran results in total quenching of the emission.
Thermodynamic and Kinetic Studies of Lanthanide(III) Complexes with H5do3ap (1,4,7,10-Tetraazacyclododecane-1,4,7-triacetic-10-(methylphosphonic Acid)), a Monophosphonate Analogue of H4dota
Authors: Táborský Petr , Lubal Přemysl , Havel Josef , Kotek Jan , Hermann Petr , Lukeš Ivan
Published: December 2005

Solution properties of complexes of a new H4dota-like ligand containing three acetate and one methylphosphonate pendant arms (H5do3ap, H5L) were studied. The ligand exhibits a high last dissociation constant (pKA = 13.83) as a consequence of the presence of phosphonate moiety. In solution, successive attachment of protons leads to several reorganizations of protonation sites and the neutral zwitterionic species H5do3ap has the same solution structure as in the solid state, where the nitrogen atom binding methylphosphonate and the opposite nitrogen atoms are protonated. Stability constants with Na+ and trivalent lanthanide ions (La3+, Ce3+, Eu3+, Gd3+, Lu3+) and Y3+ have been determined. The constants are comparable or higher than those of H4dota due to the higher overall basicity of H5do3ap. Formation of the stable protonated complexes, as well as complexes with the L:M = 1:2 stoichiometry, was proved. Formation and decomplexation kinetics of the Ce3+ and Gd3+ complexes were investigated. The mechanism of formation of the H5do3ap complexes is similar to that observed for H4dota complexes and the complex species with mono- or diprotonated ligand on the cyclen ring are considered as the reaction intermediates. Acid-assisted decomplexation of H5do3ap complexes is faster in comparison with those of H4dota. This is caused by higher basicity of the phosphonate pendant arm and the ring nitrogen atoms, which facilitates the proton transfer from the bulk solution to the nitrogen atoms of cyclen ring.
Self-Assembled Trigonal Prismatic Altitudinal Rotors with Triptycene Paddle Wheels
Authors: Caskey Douglas C. , Wang Bing , Zheng Xiaolai , Michl Josef
Published: December 2005

We describe the synthesis of a trigonal prismatic molecular rotor by self-assembly from paddlewheel carrying molecular rods and trigonal star connectors in a 3:2 ratio. The rod is 9,10-diethynyltriptycene terminated in transversely reactive [Pt(dppp)]+ groups (dppp = 1,3-bis(diphenylphosphino)propane) and the connector is 1,3,5-tris[(4-pyridyl)ethynyl]benzene. The structure of the molecular rotor has been established by 2-D NMR and MS, including diffusion-ordered NMR and collision-induced dissociation.
NOVEL SYNTHESIS OF HIGHLY PHENYL-SUBSTITUTED SPIROBIFLUORENE AND CARBAZOLE DERIVATIVES THROUGH DIELS–ALDER REACTION FOR LIGHT-EMITTING DIODES
Authors: LEE SEUNG EUN , CHO HYUN NAM , JUNG SUNG HYUN , PARK HO CHEOL , LEE CHANG JUNE , PARK JONG WOOK
Published: December 2005

We synthesized and characterized novel highly phenyl-substituted spirobifluorene and carbazole derivatives such as 3,6-bis[(2,3,4,5-tetraphenyl)phenyl]-9-ethylcarbazole (BTPEC); 3,6-bis(7,10-diphenyl-fluoranthene)-9-ethylcarbazole (BDFEC); 2,7-Bis[(2,3,4,5-tetraphenyl)phenyl]-9,9′-spirobifluorene (BTPSF); and 3,6-bis(7,10-diphenyl-fluo-ran-thene)-9,9′-spirobifluorene (BDFSF), through Diels–Alder reaction. BDFEC showed sky blue PL spectrum at 481 nm and BTPSF showed ultra-violet PL spectrum at 374 nm in chloroform solution. Also BTPEC and BDFSF exhibited PL spectrum at around the UV region, 390 and 467 nm.
WHITE-ELECTROLUMINESCENCE DEVICE BASED ON POLYMER/QUANTUM DOT NANOCOMPOSITES
Authors: PARK JONG HYEOK , PARK O OK , KIM JAI KYEONG , YU JAE-WOONG , KIM JUNG YONG , KIM YOUNG CHUL
Published: December 2005

White light emission was obtained from a light-emitting diode prepared from polymer/quantum dot nanocomposites consisting of poly(9,9′-dihexylfluorene-2,7-divinylene-m-phenylenevinylene-stat-p-phenylenevinylene) (PDHFPPV) and CdSe nanoparticles. Blue emission from PDHFPPV and red emission from the nanoparticles, which is triggered by partial excitation energy transfer from PDHFPPV, jointly contribute to white emission of the organic/inorganic hybrid device. Also, the blue-emitting matrix polymer makes the device preparation process simpler due to its high processability. By controlling the blend ratio, we could obtain a pure white color from the hybrid device.
TOWARD EFFICIENT ELECTRON-TRANSPORTING AND BLUE-EMITTING MATERIALS FOR ORGANIC LIGHT-EMITTING DIODES: STRUCTURE AND PHOTOLUMINESCENT PROPERTIES OF SILOLE DERIVATIVES
Authors: KANG YOUNGJIN , PARK JUNGCHEOL , HEO JUN , PARK KI-MIN , AHN JUN-HWAN , JUNG SUNG OUK , KIM YUN-HI , KWON SOON-KI
Published: December 2005

The potential blue-emitting as well as electron-transporting materials, 2,5-bis(3,5-trifluoromethylphenyl)-1,1-dimethyl-3,4-diphenylsilole (silole = silacyclopentadiene) (1) and 2,5-bis(3,5-trifluoromethylphenyl)-1,1-diphenyl-3,4-diphenylsilole (2), were synthesized by the Pd-mediated cross coupling reaction of corresponding bis(pheny-lethynyl)silanes with 1-bromo-3,5-trifluoromethylbenzene via intramolecular reductive cyclization. The structure of 2 was established by single-crystal X-ray diffraction analysis. In crystal structure, the dihedral angle between the functionalized phenyl groups containing CF3 at 2,5-position and central silole ring is about 48.70(6)°, showing the diminution of effective conjugation. These compounds exhibited high thermal stability without degradation up to 200°C. The absorption and photoluminescent properties, and cyclic voltametry have been evaluated. Compounds 1 and 2 in thin films showed intense blue emissions at 464–473 nm, respectively, in photoluminescence (PL). In electrochemistry, the reduction potential of 1 and 2 were at -1.92 and -1.81 V, respectively. The presence of substituents at 2,5′ — and/or 1,1′ — positions of siloe ring affected the LUMO energy levels through σ*–π* conjugation.
INORGANIC–ORGANIC HYBRID PHOTOREFRACTIVE MATERIALS BEARING THE BIFUNCTIONAL CHROMOPHORE
Authors: JUN WOONG GI , YOON HYUK , LEE SEUNG HWAN , KIM JAE HONG , CHOI DONG HOON
Published: December 2005

We prepared the photorefractive composite based on organic–inorganic hybrid materials containing charge-transporting molecules, second-order nonlinear optical chromophore, photosensitizer, and plasticizer either as a side chain unit or a guest molecule. New chromophore was synthesized to contain nonlinear optical chromophore and carbazole in one molecule. The functional chromophores were reacted to isocyanatotriethoxysilane to provide the functional precursor molecules. 2,4,7-Trinitrofluorenone (TNF) was added into the sol-gel materials to induce a charge-transfer complex. We also compared the gain coefficient of the photorefractive samples with the change of the concentration of the plasticizer, determined by two-beam coupling technique.
IRIDIUM COMPLEXES WITH 3-METHYL-2,4-PENTANEDIONE LIGAND FOR ORGANIC ELECTROLUMINESCENT DEVICE
Authors: KIM DONG UK , PAIK SEOUNG-HEY , KIM SUNG-HOON , TAK YOON-HEUNG , KIM SANG-DAE , KIM KI-DONG , JU HUI-JIN , KIM TAE-JEONG , BAEK JEONG-JU , JEONG YOUNG CHUL , PARK LEE SOON , HAN YOON SOO
Published: December 2005

Phosphorescent materials, IR-FPPA1, IR-PPA1 and IR-TPA1 as emission dopants for electroluminescent (EL) devices were synthesized. Three types of devices such as ITO/ NPD/IR-FPPA1 (6%), IR-PPA1 (6%) and IR-TPA1 (6%) in CBP/BCP/Alq/LiF/Al were fabricated. IR-FPPA1, IR-PPA1 and IR-TPA1 exhibited 540 Cd/m2, 6600 Cd/m2 and 590 Cd/m2 with their external quantum efficiency of 1.2%, 8.9% and 3.0% in current densities of 20 mA/cm2, respectively. EL spectra of the IR-FPPA1, IR-PPA1, and IR-TPA1 devices had the band maxima at 490 nm, 535 nm and 615 nm, respectively.
SYNTHESIS AND ELECTRO-OPTICAL PROPERTIES OF BLUE EMITTING POLY(BP-alt-BCV) CONJUGATED POLYMERS
Authors: BAEK JEONG JU , JEONG YOUNG CHUL , PARK LEE SOON , LEE JUNG KYUNG , HAN YOON SOO , KWON YOUNGHWAN
Published: December 2005

A new blue electroluminescent conjugated polymer, poly(BP-alt-BCV), was prepared by Hornor–Emmons polycondensation of [5-carbazol-9-yl-3-(diethoxy-phosphorylmethyl)-2-(2-ethyl-hexyloxy)-benzyl]-phosphonic acid diethyl ester (PHBP) and 4,4′-biphenyldicarboxaldehyde (BPCA) in the presence of tert-BuOK in THF. UV-visible absorption maximum (λmax,UV, π-π* transition) of poly(BP-alt-BCV) was measured at 340 nm. PL maximum (λmax,PL) values of poly(BP-alt-BCV) were obtained at 406 and 430 nm, when excited at its own λmax,UV. It was found that double layer [ITO/poly(BP-alt-BCV)/Alq3 (50 Å)/Al] PLED exhibited maximum EL peak at 440 nm and blue emission (x = 0.1794, y = 0.1878), similar to the NTSC standard blue (x = 0.14, y = 0.08).
LANTHANIDE(III)-CORED SUPRAMOLECULAR COMPLEXES WITH LIGHT-HARVESTING DENDRITIC ARRAYS FOR ADVANCED PHOTONICS APPLICATIONS
Authors: KIM HWAN KYU , BAEK NAM SEOB , OH JAE BUEM , KA JAE-WON , ROH SOO-GYUN , KIM YONG HEE , NAH MIN KOOK , HONG KYUNG-SOO , SONG BOK JOO , ZHOU GUIJIANG
Published: December 2005

We have designed and developed novel lanthanide(III)-cored supramolecular systems with light-harvesting dendritic arrays for advanced photonics applications such as planar waveguide amplifiers, plastic lasers, and light-emitting diodes. The supramolecular ligands, such as naphthalenes and metalloporphyrins, were specially designed and synthesized in order to provide enough coordination sites to form stable lanthanide(III)-chelated complexes. The energy levels of the supramolecular ligands were tailored to maintain the effective energy transfer process from supramolecular ligands to lanthanide(III) ions for getting a higher optical amplification gain. Also, efficient energy transfer pathways for the sensitization of lanthanide ions by supramolecular ligands were investigated, for the first time to the best our knowledge. Furthermore, to enhance the optophysical properties of novel supramolecular systems, aryl ether-functionalized dendrons as photon antennas have been incorporated into lanthanide-cored supramolecular systems, yielding novel lanthanide-cored dendritic materials with efficient site-isolation effect.
THERMALLY STABLE PERFLUORINATED POLYIMIDES WITH PENDANT PERFLUORINATED AROMATIC UNIT FOR PHOTONIC APPLICATIONS
Authors: PARK JIN KYU , SONG BOK JU , LEE DONG-HUN , SONG YOUNG-BAE , OH JAE BUEM , HONG JI-SOOK , KIM HWAN KYU
Published: December 2005

We have designed and synthesized novel thermally stable perfluorinated polyimides with pendant perfluorinated aromatic unit for photonic applications. At first, we developed a new synthetic route to a perfluorinated aromatic diamine by protecting-deprotecting as well as by nucleophilic bromine displacement reactions, affording a new diamine with a pendant perfluorinated aromatic unit. Its chemical structure was identified by 1H- , 19F- and 13C-NMR spectroscopies as well as mass spectrometry. Novel fluorinated polyimides were prepared by condensation polymerization of the present fluorinated diamine with various dianhydrides. The resultant polyimides are thermally stable over 400°C. The refractive index and birefringence of the resultant polyimides are 1.5844 ~ 1.5040 and 0.01 ~ 0.03 at 633 nm, respectively.
SYNTHESIS OF POLY(DIPROPARGYLFLUORENE) BY THE PALLADIUM-CATALYZED CROSS COUPLING REACTION AND ITS LUMINESCENT PROPERTIES
Authors: LEE SANG-GU , KWAK YOUNG-WOO , PARK JONG-WOOK , JIN SUNG-HO , GAL YEONG-SOON
Published: December 2005

Poly(9,9-dipropargylfluorene) [PDPF] was prepared via oxidative coupling reaction of dipropargylfluorene in the presence of (PPh3)2PdCl2/CuI without oxygen in high yield. The polymer structure was characterized by the instrumental methods such as NMR, IR, and UV-visible spectroscopies to have the designed chemical structure. PDPF showed characteristic UV-visible absorption band at 338 nm and blue PL spectrum at 417 nm corresponding to the photon energy of 2.98 eV under the excitation wavelength of 350 nm. The bandgap energy of this material was estimated to be 3.67 eV from the analysis of the absorption edge.
SIMULTANEOUS ACQUISITION OF SIGNALS AND IMAGES: APPLICATIONS IN SPORTS MEDICINE AND NEUROLOGY
Authors: CORAZZA IVAN , BOTTEGHI MATTEO , TERENZIANI CORINNA , ZANNOLI SEBASTIANO , LATESSA PASQUALINO MAIETTA , TENTONI CLAUDIO
Published: December 2005

In some medical applications, the simultaneous acquisition of signals corresponding to physiological parameters and video recording allows a more accurate analysis of the problem and a more complete diagnosis. In rehabilitation, the correlation between parameters of interest (angles, speed, power, EMG) and images of the patient's movements is important to devise an adequate training protocol. In neurology, some pathologies need to be investigated by a comparison of images and EEG signals. Nowadays, commonly used systems are made up of two different apparatuses: one for signals acquisition and one for video recording. They are separate pieces of equipment, and the integration between data and video is possible only to the detriment of information and the possibility to make quantitative analysis. This paper describes a new digital system for the concomitant acquisition of signals and video. It is a low cost instrumentation, PC based and easy-to-use. Data and video are recorded in standard formats and can be analyzed in a post-acquisition stage. The time resolution of the system is given by the video frame rate (25 fps), although an A/D conversion system allows frequencies up to 8000 Hz. The prototype was tested to verify synchronism between data and frames, and differences smaller than the resolution (40 ms) were found. The feasibility of the system was checked in two different applications: rehabilitation training with an isotonic Leg Extension and a daily EEG examination of one patient at the Neurological Institute of Bologna University. Both the applications gave good results in terms of time resolution, synchronism and user-friendliness.
EVALUATION OF THE MAXIMAL THEORETICAL FORCE EXERTED BY THE LEGS, WITH AN ISOTONIC LEG EXTENSION MACHINE
Authors: CORAZZA IVAN , CAROLI ELENA , ZANNOLI SEBASTIANO , ZANNOLI ROMANO , LATESSA PASQUALINO MAIETTA , TENTONI CLAUDIO
Published: December 2005

Evaluating the maximal force exertable by a subject in a particular exercise is an important starting step in setting up rehabilitation and training programs. The current reference procedure is the isokinetic approach, which has some limitations due to poor physiological agreement and high cost of the equipment. This paper describes a method for evaluating maximal force using an isotonic approach. The maximal force value is extrapolated from the linear behavior of the relationship between the force and the maximal velocity at lower loads. The method was applied to a group of 25 students at the Sports Medicine Faculty, University of Bologna using a leg extension AirMachine (919 Tech). Loads were settled adopting a step-up protocol and the maximal velocity was calculated by measuring the instantaneous angle of the lever. The linear correlation coefficient between the settled loads and the maximal velocity ranged between 0.5679 and 0.9980 for the right leg and between 0.6791 and 0.9895 for the left leg, and the maximal estimated force ranged between 26.9 kg and 248.2 kg for the right leg and between 32.6 kg and 221.9 kg for the left leg. The method showed a good feasibility and an acceptable error level, and can be proposed as an alternative to the isokinetic approach.
CONTROL OF ERRORS USING A SIMPLIFIED CLINICAL SETUP FOR MOTION ANALYSIS: ERRORS DUE TO CALIBRATION AND THREE-DIMENSIONAL RECONSTRUCTION
Authors: BERTHONNAUD ERIC , DIMNET JOANNÈS
Published: December 2005

Different systems of motion analysis have been described. They usually associate several cameras with a force platform. They can analyze very sophisticated human movements. They are, however, expensive and require significant technical formation from users. A new system is proposed for simple and standard clinical applications. It uses only two cameras and a coupled force plate delivering only the vertical component of the patient weight and the location of his center of mass. It is inexpensive, simple to use and delivers accurate results. This is obtained through a strict experimental protocol, and a new method of data treatment which allows the control of errors at each step of the successive calculations. This paper describes the new system, the new calibration procedure and the control of errors.
INVERSE DYNAMICS MODELING IN GAIT ANALYSIS: AN APPLICATION
Authors: DAVINELLI MARIO , STAGNI RITA , FANTOZZI SILVIA , CAPPELLO ANGELO
Published: December 2005

A method based on inverse dynamics modeling for the subject specific in vivo evaluation of muscle activity in one subject during the execution of chair rising is being described in this article.

The calculation of net joint loads and moments is performed through the solution of Newton–Euler mechanics applied to each body segment. Accuracy in the calculation of these quantities is a prerequisite for the reliability of the final results. This accuracy depends on several modeling factors: the choice of the inertial parameters data-set was specifically investigated here. This choice did not result in relevantly affecting the accuracy of the calculated net joint loads for stair ascending and descending, thus even more for a slow motor task like chair rising. Thus, the choice of an inertial parameter data set from the literature was acceptable for the specific application. In order to solve the undetermined problem, the method for the estimation of the contribution of each muscle from internal joint loads and moments was based on static optimization. The static optimization allowed for the estimation of the time histories of the force exerted by each muscolo-tendineous modeled actuator. Among these, the Rectus Femoris exerted the maximum force. In conclusion, the preliminary results obtained with the proposed method allowed for obtaining a realistic estimate of the force exerted in vivo by each muscle during the execution of chair rising-sitting motor task. This is promising in gaining a better understanding on the biomechanical role of muscles during every day living motor tasks, and for the planning and evaluation of surgical and/or rehabilitative procedures.
Analysis of glucose metabolism in diabetic rat retinas
Authors: Ola M. Shamsul , Berkich Deborah A. , Xu Yuping , King M. Todd , Gardner Thomas W. , Simpson Ian , LaNoue Kathryn F.
Published: December 2005

This study was conceived in an effort to understand cause and effect relationships between hyperglycemia and diabetic retinopathy. Numerous studies show that hyperglycemia leads to oxidative stress in the diabetic retinas, but the mechanisms that generate oxidative stress have not been resolved. Increased electron pressure on the mitochondrial electron transfer chain, increased generation of cytosolic NADH, and decreases in cellular NADPH have all been cited as possible sources of reactive oxygen species and nitrous oxide. In the present study, excised retinas from control and diabetic rats were exposed to euglycemic and hyperglycemic conditions. Using a microwave irradiation quenching technique to study retinas of diabetic rats in vivo, glucose, glucose-derived metabolites, and NADH oxidation/reduction status were measured. Studying excised retinas in vitro, glycolytic flux, lactate production, and tricarboxylic acid cycle flux were evaluated. Enzymatically assayed glucose 6-phosphate and fructose 6-phosphate were only slightly elevated by hyperglycemia and/or diabetes, but polyols were increased dramatically. Cytosolic NADH-to-NAD ratios were not elevated by hyperglycemia nor by diabetes in vivo or in vitro. Tricarboxylic acid cycle flux was not increased by the diabetic state nor by hyperglycemia. On the other hand, small increases in glycolytic flux were observed with hyperglycemia, but glycolytic flux was always lower in diabetic compared with control animals. An observed decrease in activity of glyceraldehyde-3-phosphate dehydrogenase may be partially responsible for slow glycolytic flux for retinas of diabetic rats. Therefore, it is concluded that glucose metabolism, downstream of hexokinase, is not elevated by hyperglycemia or diabetes. Metabolites upstream of glucose such as the sorbitol pathway (which decreases NADPH) and polyol synthesis are increased.
Cytokine-induced metabolic effects in human adipocytes are independent of endogenous nitric oxide
Authors: Linscheid Philippe , Seboek Dalma , Zulewski Henryk , Scherberich Arnaud , Blau Nenad , Keller Ulrich , Müller Beat
Published: December 2005

Nitric oxide (NO) has been recognized as a potential mediator of inflammation-induced metabolic alterations, including insulin resistance. However, expression mechanisms and potential roles of endothelial and inducible NO synthases (eNOS and iNOS, respectively) in human adipocytes are poorly understood. In the present study, we aimed to analyze several aspects of NO-related gene expression and metabolite synthesis in basal and inflammation-activated human adipocyte models. eNOS mRNA was highly expressed in omental and to a lesser extent in human subcutaneous adipose tissue biopsies, but not in purified adipocytes, in mesenchymal stem cell (MSC)- and in preadipocyte-derived adipocytes, respectively. Trace amounts of iNOS mRNA were detected in adipose tissue samples of donors with abdominal infection, as opposed to noninfected subjects. Interferon-γ, in combination with interleukin-1β or lipopolysaccharide, evoked a transient (4 h < time < 24 h) iNOS mRNA expression in human MSC and preadipocyte-derived adipocytes, respectively. This induction was preceded by cytokine-specific mRNAs. In addition, it was accompanied by an activation of the tetrahydrobiopterin synthesis pathway and by inhibition of peroxisome proliferator-activated receptor-γ2. In contrast to murine 3T3-L1-derived adipocytes, iNOS protein and NO oxidation products remained undetectable in iNOS mRNA-positive human adipocytes. Accordingly, coadministration of NOS inhibitors (i.e., Nω-nitro-l-arginine methyl ester, Nω-monomethyl-l-arginine, and 1400W) had no effects on insulin-mediated glucose uptake and lipolysis. We conclude that, in human adipocytes, endogenous NO is not involved in metabolic regulation during either basal or cytokine-activated conditions.
Endocrine responses to acute and chronic high-altitude exposure (4,300 meters): modulating effects of caloric restriction
Authors: Barnholt Kimberly E. , Hoffman Andrew R. , Rock Paul B. , Muza Stephen R. , Fulco Charles S. , Braun Barry , Holloway Leah , Mazzeo Robert S. , Cymerman Allen , Friedlander Anne L.
Published: December 2005

High-altitude anorexia leads to a hormonal response pattern modulated by both hypoxia and caloric restriction (CR). The purpose of this study was to compare altitude-induced neuroendocrine changes with or without energy imbalance and to explore how energy sufficiency alters the endocrine acclimatization process. Twenty-six normal-weight, young men were studied for 3 wk. One group [hypocaloric group (HYPO), n = 9] stayed at sea level and consumed 40% fewer calories than required to maintain body weight. Two other groups were deployed to 4,300 meters (Pikes Peak, CO), where one group (ADQ, n = 7) was adequately fed to maintain body weight and the other [deficient group (DEF), n = 10] had calories restricted as above. HYPO experienced a typical CR-induced reduction in many hormones such as insulin, testosterone, and leptin. At altitude, fasting glucose, insulin, and epinephrine exhibited a muted rise in DEF compared with ADQ. Free thyroxine, thyroid-stimulating hormone, and norepinephrine showed similar patterns between the two altitude groups. Morning cortisol initially rose higher in DEF than ADQ at 4,300 meters, but the difference disappeared by day 5. Testosterone increased in both altitude groups acutely but declined over time in DEF only. Adiponectin and leptin did not change significantly from sea level baseline values in either altitude group regardless of energy intake. These data suggest that hypoxia tends to increase blood hormone concentrations, but anorexia suppresses elements of the endocrine response. Such suppression results in the preservation of energy stores but may sacrifice the facilitation of oxygen delivery and the use of oxygen-efficient fuels.
Megalin binds and internalizes angiotensin-(1–7)
Authors: Gonzalez-Villalobos Romer , Klassen R. Bryan , Allen Patricia L. , Johanson Kelly , Baker Chasity B. , Kobori Hiroyuki , Navar L. G. , Hammond Timothy G.
Published: December 2005

Megalin is a multiligand receptor heavily involved in protein endocytosis. We recently demonstrated that megalin binds and mediates internalization of ANG II. Although there is a strong structural resemblance between ANG II and ANG-(1–7), their physiological actions and their affinity for the angiotensin type 1 receptor (AT1R) are dissimilar. Therefore, the hypothesis of the present work was to test whether megalin binds and internalizes ANG-(1–7). The uptake of ANG-(1–7) was determined by exposure of confluent monolayers of BN/MSV cells (a model representative of the yolk sac epithelium) to fluorescently labeled ANG-(1–7) (100 nM) and measurement of the amount of cell-associated fluorescence after 4 h by flow cytometry. Anti-megalin antisera and an AT1R blocker (olmesartan) were used to interfere with uptake via megalin and the AT1R, respectively. ANG-(1–7) uptake was prevented by anti-megalin antisera (63%) to a higher degree than olmesartan (13%) ( P < 0.001). In analysis by flow cytometry of binding experiments performed in brush-border membrane vesicles isolated from kidneys of CD-1 mice, anti-megalin antisera interfered with ANG-(1–7) binding more strongly than olmesartan ( P < 0.05 against positive control). Interactions of megalin with ANG-(1–7) at a molecular level were studied by surface plasmon resonance, demonstrating that ANG-(1–7) binds megalin dose and time dependently and with an affinity similar to ANG II. These results show that the scavenger receptor megalin binds and internalizes ANG-(1–7).
Angiotensin II AT2receptors inhibit proximal tubular Na+-K+-ATPase activity via a NO/cGMP-dependent pathway
Authors: Hakam Amer C. , Hussain Tahir
Published: December 2005

Angiotensin II AT2receptors act as a functional antagonist for the AT1receptors in various tissues. We previously reported that activation of the renal AT2receptors promotes natriuresis and diuresis; however, the mechanism is not known. The present study was designed to investigate whether activation of AT2receptors affects the activity of Na+-K+-ATPase (NKA), an active tubular sodium transporter, in the proximal tubules isolated from Sprague-Dawley rats. The AT2receptor agonist CGP-42112 (10−10-10−7M) produced a dose-dependent inhibition of NKA activity (9–38%); the inhibition was attenuated by the presence of the AT2receptor antagonist PD-123319 (1 μM), suggesting the involvement of the AT2receptors. The AT1receptor antagonist losartan (1 μM) did not affect the CGP-42112 (100 nM)-induced inhibition of NKA activity. The presence of guanylyl cyclase inhibitor ODQ (10 μM) and the nitric oxide (NO) synthase inhibitor Nω-nitro-l-arginine methyl ester (l-NAME; 100 μM) abolished the CGP-42112 (100 nM)-induced NKA inhibition. ANG II (100 nM), in the presence of losartan, significantly inhibited NKA activity; the inhibition was attenuated by PD-123319. CGP-42112 also, in a dose-dependent manner, stimulated NO production (∼0–230%) and cGMP accumulation (∼25–100%). The CGP-42112 (100 nM)-induced NO and cGMP increases were abolished by the AT2receptor antagonist PD-123319, ODQ, and l-NAME. The data suggest that the activation of the AT2receptor via stimulation of the NO/cGMP pathway causes inhibition of NKA activity in the proximal tubules. This phenomenon provides a plausible mechanism responsible for the AT2receptor-mediated natriuresis-diuresis in rodents.
Role of fibrillin-1 in hypertensive and diabetic glomerular disease
Authors: Hartner Andrea , Schaefer Liliana , Porst Markus , Cordasic Nada , Gabriel Anke , Klanke Bernd , Reinhardt Dieter P. , Hilgers Karl F.
Published: December 2005

The microfibrillar protein fibrillin-1 is a component of the mesangial matrix. Defects in fibrillin-1 predisposes individuals to vascular damage in Marfan syndrome, but the role of fibrillin-1 in kidney disease is unknown. We hypothesized that fibrillin-1 is involved in hypertensive or diabetic glomerular disease. DOCA-salt hypertension or streptozotocin (STZ) diabetes led to a significant increase in glomerular fibrillin-1 deposition. To test the functional role of fibrillin-1, DOCA hypertension and STZ diabetes were induced in mice homozygous for a mutation leading to a fivefold lower expression of fibrillin-1 (mgR/mgR). Untreated male mgR/mgR mice usually die from aortic dissection during the first 4 mo of life. All DOCA-treated mgR/mgR mice died within 2 wk after onset of DOCA treatment. DOCA-treated heterozygous (mgR/+) and their wild-type littermates displayed similar blood pressure levels, but albuminuria was significantly lower in mgR/+ than in wild-type mice after DOCA treatment. Similarly, STZ diabetic mgR/mgR and mgR/+ developed lower albuminuria than wild-type mice despite higher blood glucose levels in mgR/mgR and mgR/+ compared with wild-type mice. Blood pressure, blood glucose, and albuminuria did not differ among untreated mgR/mgR, mgR/+, and wild-type mice, respectively. In diabetic mgR/+ and mgR/mgR, but not in wild-type mice, an induction of glomerular decorin expression was observed. Thus underexpression of fibrillin-1 predisposes individuals to lethal aortic dissection in the presence of hypertension. On the other hand, albuminuria as a parameter of microvascular damage in hypertension and diabetes was ameliorated in fibrillin-1-underexpressing mice, possibly due to a compensatory upregulation of decorin. We conclude that fibrillin-1 may contribute to glomerular damage in hypertensive and diabetic kidney disease.
Molecular characterization of the mercurial sensitivity of a frog urea transporter (fUT)
Authors: Stewart Gavin S. , Smith Craig P. , Cooper Gordon J.
Published: December 2005

The amphibian urea transporter (fUT) shares many properties with the mammalian urea transporters (UT) derived from UT-A and UT-B genes. The transport of urea by fUT is inhibited by the mercurial agent p-chloromercuribenzenesulfonic acid (pCMBS). We found that in oocytes expressing cRNA encoding fUT, a 5-min preincubation in 0.5 mM mercury chloride (HgCl2) also significantly reduced urea uptake. The transport of urea by fUT was rendered mercury (Hg2+) insensitive by mutating either of the residues C185 or H187, both of which lie within the M-I region (close to the hypothetical UT pore). In oocytes expressing a mixture of the C185 and H187 mutants, Hg2+sensitivity was reestablished. The transport of urea by the mouse UTs mUT-A2 and mUT-A3 was not sensitive to Hg2+. Introducing cysteine residues analogous to that mutated in fUT into mUT-A2 or mUT-A3 did not induce Hg2+sensitivity. Additionally, introducing the double cysteine, histidine mutations into mUT-A2 or mUT-A3 still did not induce Hg2+sensitivity, indicating that a region outside of the M-I region also contributes to the Hg2+-induced block of fUT. Using a series of chimeras formed between UT-A3 and fUT, we found that as well as C185 and H187, residues within the COOH terminal of fUT determine Hg2+sensitivity, and we propose that differences in the folding of this region between fUT and mUT-A2/mUT-A3 allow access of Hg2+to the fUT channel pore.
Endothelin-1 stimulates NO production and inhibits cAMP accumulation in rat inner medullary collecting duct through independent pathways
Authors: Stricklett Peter K. , Hughes Alisa K. , Kohan Donald E.
Published: December 2005

Endothelin-1 (ET-1) inhibition of vasopressin (AVP)-stimulated cAMP accumulation in the collecting duct has been hypothesized to be mediated, at least in part, by nitric oxide (NO). To examine this, the effect of ET-1 on NO production by acutely isolated rat inner medullary collecting duct (IMCD) cell suspensions and the role of NO in mediating ET-1 effects on AVP-stimulated cAMP accumulation were studied. ET-1 dose dependently (first evident at 100 pM ET-1) increased IMCD NO production as determined by DAF-FM fluorescence. ETBreceptor (BQ-788), but not ETAreceptor (BQ-123), antagonism blocked this effect. Nonspecific NO synthase (NOS) inhibitors [ NG-nitro-l-arginine methyl ester (l-NAME) or NG-monomethyl-l-arginine] or NOS-1 inhibitors (SMTC or VNIO) inhibited the ET-1 response, whereas NOS-2 or NOS-3 inhibitors (l-NAA or 1400W) were ineffective. ET-1 also increased cGMP accumulation. ET-1 caused a 35% reduction in AVP-stimulated cAMP levels; however, this response was not affected by l-NAME or SMTC. The addition of l-arginine, NADPH, tetrahydrobiopterin, or tempol (to reduce superoxide-dependent conversion of NO to peroxynitrate) did not affect the response. NO donors (SNAP or spermine NONOate), at concentrations that stimulated DAF-FM fluorescence and increased cGMP levels, did not alter AVP-stimulated cAMP accumulation in the IMCD cell suspensions. In conclusion, ET-1 stimulates IMCD NO production through activation of the ETBreceptor and NOS-1. However, neither ET-1-mediated NO production nor NO donors inhibit AVP-stimulated cAMP accumulation, indicating that NO does not mediate ET-1 inhibition of cAMP production by the IMCD.
Altered Inhibition in Lateral Amygdala Networks in a Rat Model of Temporal Lobe Epilepsy
Authors: Benini Ruba , Avoli Massimo
Published: December 2005

Clinical and experimental evidence indicates that the amygdala is involved in limbic seizures observed in patients with temporal lobe epilepsy. Here, we used simultaneous field and intracellular recordings from horizontal brain slices obtained from pilocarpine-treated rats and age-matched nonepileptic controls (NECs) to shed light on the electrophysiological changes that occur within the lateral nucleus (LA) of the amygdala. No significant differences in LA neuronal intrinsic properties were observed between pilocarpine-treated and NEC tissue. However, spontaneous field activity could be recorded in the LA of 21% of pilocarpine-treated slices but never from NECs. At the intracellular level, this network activity was characterized by robust neuronal firing and was abolished by glutamatergic antagonists. In addition, we could identify in all pilocarpine-treated LA neurons: 1) large amplitude depolarizing postsynaptic potentials (PSPs) and 2) a lower incidence of spontaneous hyperpolarizing PSPs as compared with NECs. Single-shock stimulation of LA networks in the presence of glutamatergic antagonists revealed a biphasic inhibitory PSP (IPSP) in both NECs and pilocarpine-treated tissue. The reversal potential of the early GABAA receptor–mediated component, but not of the late GABAB receptor–mediated component, was significantly more depolarized in pilocarpine-treated slices. Furthermore, the peak conductance of both fast and late IPSP components had significantly lower values in pilocarpine-treated LA cells. Finally, paired-pulse stimulation protocols in the presence of glutamatergic antagonists revealed a less pronounced depression of the second IPSP in pilocarpine-treated slices compared with NECs. Altogether, these findings suggest that alterations in both pre- and postsynaptic inhibitory mechanisms contribute to synaptic hyperexcitability of LA networks in epileptic rats.
Uteroplacental insufficiency affects epigenetic determinants of chromatin structure in brains of neonatal and juvenile IUGR rats
Authors: Ke X. , Lei Q. , James S. J. , Kelleher S. L. , Melnyk S. , Jernigan S. , Yu X. , Wang L. , Callaway C. W. , Gill G. , Chan G. M. , Albertine K. H. , McKnight R. A. , Lane R. H.
Published: December 2005

Intrauterine growth retardation (IUGR) increases the risk of neuroendocrine reprogramming. In the rat, IUGR leads to persistent changes in cerebral mRNA levels. This suggests lasting alterations in IUGR cerebral transcriptional regulation, which may result from changes in chromatin structure. Candidate nutritional triggers for these changes include altered cerebral zinc and one-carbon metabolite levels. We hypothesized that IUGR affects cerebral chromatin structure in neonatal and postnatal rat brains. Rats were rendered IUGR by bilateral uterine artery ligation; controls (Con) underwent sham surgery. At day of life 0 (d0), we measured cerebral DNA methylation, histone acetylation, expression of chromatin-affecting enzymes, and cerebral levels of one-carbon metabolites and zinc. At day of life 21 (d21), we measured cerebral DNA methylation and histone acetylation, as well as the caloric content of Con and IUGR rat breast milk. At d0, IUGR significantly decreased genome-wide and CpG island methylation, as well as increased histone 3 lysine 9 (H3/K9) and histone 3 lysine 14 (H3/K14) acetylation in the hippocampus and periventricular white matter, respectively. IUGR also decreased expression of the chromatin-affecting enzymes DNA methyltransferase 1 (DNMT1), methyl-CpG binding protein 2 (MeCP2), and histone deacetylase (HDAC)1 in association with increased cerebral levels of zinc. In d21 female IUGR rats, cerebral CpG DNA methylation remained lower, whereas H3/K9 and H3/K14 hyperacetylation persisted in hippocampus and white matter, respectively. In d21 male rats, IUGR decreased acetylation of H3/K9 and H3/K14 in these respective regions compared with controls. Despite these differences, caloric, fat, and protein content were similar in breast milk from Con and IUGR dams. We conclude that IUGR results in postnatal changes in cerebral chromatin structure and that these changes are sex specific.
Safety and Tolerability of Ultra-Rush Induction, Less than One Hour, of Sublingual Immunotherapy in Children
Authors: Tripodi S. , Di Rienzo Businco A. , Benincori N. , Scala G. , Pingitore G.
Published: December 2005

Background: The safety and tolerability of sublingual immunotherapy (SLIT) has been documented in allergic patients both in the build-up phase as well as during maintenance, but only two studies have evaluated the occurrence of adverse reactions with an ultra-rush regimen of SLIT induction in a mixed paediatric/adult population. Moreover one of these two studies used a chemically modified extract (allergoid). The aim of the present study was to evaluate the occurrence of immediate or late adverse reactions in allergic children after a very fast (40 min) ultra-rush SLIT induction with two different allergen extract solutions. Methods: We studied 100 children (64 boys, mean age of 9.6 years, range 3.5–16.8), with a history of intermittent/persistent rhinitis and/or intermittent/mild persistent asthma due to inhalant allergens. The ultra-rush build-up phase involved the administration, every 10 min, of increasing doses of the highest-concentration vial of SLIT of two different manufacturers (Anallergo and Stallergènes). Results: All patients completed the treatment, side-effects have been recorded in 19% of the cases: 10% within 1 h after the build-up phase, 7% within 48 h and 2% mixed. A major difference (p = 0.0001) was recorded between Anallergo (6 patients, 8.7%) and Staloral (13 patients, 41.9%), but all the reactions were mild: principally oral symptoms, in 1 case rhinorrhoea and cough, and delayed abdominal pain and diarrhoea in another patient. Conclusions: No severe adverse reactions were observed with this ultra-rush SLIT induction also in the paediatric age; statistical differences have been documented between the two different extracts.
Safety of an Ultra-Rush Immunotherapy Build-Up Schedule with Therapeutic Vaccines Containing Depigmented and Polymerized Allergen Extracts
Authors: Casanovas M. , Martín R. , Jiménez C. , Caballero R. , Fernández-Caldas E.
Published: December 2005

Background: Four administration schedules of immunotherapy have been reported: conventional, cluster, rush and ultra-rush. Objectives: To evaluate the safety and the clinical advantage of using standardized modified allergen extracts in an ultra-rush protocol without premedication and/or hospitalization. Material and Methods: One thousand and sixty-eight patients with rhinoconjunctivitis and/or asthma sensitized to mites and/or pollen were included in a prospective observational study. Patients received a therapeutic vaccine containing depigmented and glutaraldehyde-modified extracts (mites and/or pollens) adsorbed onto alum prescribed by a specialist. The schedule of administration consisted of injecting 0.2 and 0.3 ml of the vial of maximum concentration during the first day of immunotherapy, separated by a time interval of 30 min. All patients reached the maximum dose (0.5 ml) after 2 injections. Tolerance was assessed by recording all side reactions related to immunotherapy, classified according to the criteria of the EAACI. Results: The total number of injections was 2,136. All patients reached the maximum established dose on the 1st day. No premedication was used. Seven clinically relevant local reactions were recorded. The systemic reactions were 5 grade-1 (2 immediate and 3 delayed) and 3 delayed grade-2 reactions. Conclusions: The therapeutic vaccines containing chemically modified extracts can be administered using an alternative ultra-rush schedule in an immunotherapy unit, reaching the maximum dose on the 1st day with 2 injections, without the need of premedication and/or hospitalization.
The Innate Immune System and Its Role in Allergic Disorders
Authors: Vandenbulcke Liesbet , Bachert Claus , van Cauwenberge Paul , Claeys Sofie
Published: December 2005

Background: There has been an increasing prevalence of allergic diseases in the Western world over the last decades. The hygiene hypothesis has been proposed as a possible explanation for this epidemical trend in allergy. A key role in this theory is assigned to the reduced microbial stimulation of the Toll-like receptors (TLRs) in early life, which could lead to a weaker Th1 response and a stronger Th2 response to allergens. The individual immunological response is determined by the interplay between the dose and timing of exposure to endotoxins, other environmental factors and genetic predisposition. In the development and progression of allergic disorders, the innate immune system plays an important role. Objective: In this review, we discuss the paradoxical effects that may appear when the innate immune components are triggered. We review the influence of changes in the gene sequence and TLR expression in relation to the overall pattern of commensals and pathogens. We explored the possibility of alternative stimulations of the immune system by CpG oligodeoxynucleotides and probiotics as therapeutic devices against this endemic disease in Western society. Methods: Selection of papers was based on the importance of their contribution to the understanding of innate immunity and its implications. Results and Conclusion: The innate immune system plays an important role in both the protection against and the enhancement of allergic disorders, but the mechanisms are still unclear. Nevertheless, gene polymorphisms and triggers of the innate immune system provide therapeutic targets for protection against and treatment of allergic disorders.
Immune-Enhancing Role of Vitamin C and Zinc and Effect on Clinical Conditions
Authors: Wintergerst Eva S. , Maggini Silvia , Hornig Dietrich H.
Published: December 2005

Vitamin C concentrations in the plasma and leukocytes rapidly decline during infections and stress. Supplementation of vitamin C was found to improve components of the human immune system such as antimicrobial and natural killer cell activities, lymphocyte proliferation, chemotaxis, and delayed-type hypersensitivity. Vitamin C contributes to maintaining the redox integrity of cells and thereby protects them against reactive oxygen species generated during the respiratory burst and in the inflammatory response. Likewise, zinc undernutrition or deficiency was shown to impair cellular mediators of innate immunity such as phagocytosis, natural killer cell activity, and the generation of oxidative burst. Therefore, both nutrients play important roles in immune function and the modulation of host resistance to infectious agents, reducing the risk, severity, and duration of infectious diseases. This is of special importance in populations in which insufficient intake of these nutrients is prevalent. In the developing world, this is the case in low- and middle-income countries, but also in subpopulations in industrialized countries, e.g. in the elderly. A large number of randomized controlled intervention trials with intakes of up to 1 g of vitamin C and up to 30 mg of zinc are available. These trials document that adequate intakes of vitamin C and zinc ameliorate symptoms and shorten the duration of respiratory tract infections including the common cold. Furthermore, vitamin C and zinc reduce the incidence and improve the outcome of pneumonia, malaria, and diarrhea infections, especially in children in developing countries.