bluuebunny/crossref_metadata_2025 huggingface dataset:
Seasonal enrichment and depletion of Hg and SO4 in Little Rock Lake: relationship to seasonal changes in atmospheric deposition
Authors: Watras C J , Morrison K A , Kratz T K
Published: November 2002

Hg and SO4 are priority pollutants in fresh waters throughout the northern hemisphere; both have atmospheric sources associated with anthropogenic emissions to the lower troposphere. Although depositional change has had a demonstrable impact on lakes over decadal time scales, effects over shorter time scales remain uncertain. To better understand the responsiveness of lakes to changing pollutant inputs, we examined the coupling of water chemistry to atmospheric deposition over time scales of weeks to years in Little Rock Lake. The results indicate that the lake is tightly coupled to its air shed with respect to Hg. The annual cycle of Hg in surface waters closely tracks the annual cycle of Hg in precipitation. For SO4, the annual cycle in lake water is damped and not in phase with the cycle of atmospheric deposition because of more intense internal recycling. These observations are in keeping with the residence times of Hg and S in lake water (Hg in months; S in years). Nevertheless, because atmospheric deposition is the dominant source of both pollutants, trends in lake water track trends in precipitation over a decadal time scale. Thus, remote lakes may be highly responsive to short term changes in Hg deposition, whereas responses to SO4 deposition may be more gradual.
Microbial utilization of dissolved organic carbon leached from riparian litterfall
Authors: McArthur Michael D , Richardson John S
Published: November 2002

Dissolved organic carbon (DOC) in aquatic systems is abundant and used within stream food webs, but DOC quality is rarely studied. DOC in the leachates from the litter of five tree species (red alder, Alnus rubra; vine maple, Acer circinatum; western red cedar, Thuja plicata; western hemlock, Tsuga hetrophylla; and Douglas-fir, Pseudotsuga menziesii) were assessed for their chemistry and relative ability to support growth of heterotrophic, stream bacteria. Bacterial growth was measured using [3H]leucine incorporated into protein over 24 h of exposure to nutrient-amended leachates. Bacterial growth was greatest in deciduous and western red cedar leachates, controlling for DOC concentration. Bacterial growth rates on most leachates were greatest after 1 h and then declined in a negative exponential pattern. The DOC less than 10 kDa supported lower bacterial growth rates than DOC from whole leachates on a per milligram DOC basis. The DOC C:N atomic ratio was the best predictor of bacterial growth (r2 = 0.84). DOC release from western hemlock needles increased linearly during 7 days of leaching, whereas most red alder and western red cedar DOC was released after 1 and 2 days, respectively. Successional changes in composition of riparian forest trees may influence the stream microbial productivity based on the changes in dissolved organic carbon.
Ligand scrambling reactions of cyano(thione)gold(I) complexes and determination of their equilibrium constants
Authors: Ahmad Saeed , Isab Anvarhusein A , Perzanowski Herman P
Published: November 2002

Ligand scrambling reactions in cyano(thione)gold(I) complexes ([>C=S-Au-CN]) to form [Au(>C=S)2]+ and [Au(CN)2] species have been investigated for a series of thiones in DMSO using 13C and 15N NMR spectroscopy. Rapid approach to equilibrium occurred and resulted in distinct signals for the [>C=S-Au-CN] and [Au(CN)2] complexes, both in 13C and 15N NMR. Equilibrium constants (Keq) were determined for scrambling of all the complexes by integrating the CN resonances in the 13C NMR recorded at 298 K. The influence of various factors (initial concentration, ionic strength, temperature, and solvent polarity) on the Keq value was examined for a representative complex (ImtAuCN (Imt = Imidazolidine-2-thione)).Key words: cyanogold(I) complexes, thiones, ligand scrambling, NMR, Keq.
Aspects of the hydrolysis of formamide: revisitation of the water reaction and determination of the solvent deuterium kinetic isotope effect in base
Authors: Slebocka-Tilk H , Sauriol F , Monette Martine , Brown R S
Published: November 2002

A study of the hydrolysis of formamide is reported with the aims of isolating the water reaction for hydrolysis from the acid and base hydrolysis terms and determining the solvent deuterium kinetic isotope effect (dkie) on base-catalyzed hydrolysis. Respective activation parameters (ΔHand ΔS) of (17.0 ± 0.4) kcal mol1and (18.8 ± 1.3) cal mol1K1for the acid reaction and (17.9 ± 0.2) kcal mol1and (11.1 ± 0.5) cal mol1K1for the base reaction were determined from Eyring plots of the second-order rate constants over the range of 27120°C. Kinetic studies at the minima of the pH/rate profiles in the pH range from 5.6 to 6.2 in MES buffers at 56°C, and in the pH range of 4.256.87 in acetate and phosphate buffers at 120°C are reported. At 56°C the available data fit the expression k56obs= 0.00303[H3O+] + 0.032[HO] + (3.6 ± 0.1) × 109, while at 120°C the data fit k120obs= (0.15 ± 0.02)[H3O+] + (3.20 ± 0.24)[HO] + (1.09 ± 0.29) × 106. Preliminary experimental estimates of Ea(ln A) of 22.5 kcal mol1(15.03) for the water rate constant (kw) are calculated from an Arrhenius plot of the 56 and 120°C data giving an estimated kwof 1.1 × 1010s1(t1/2= 199 years) at 25°C. Solvent dkie values of kOH/kOD= 1.15 and 0.77 ± 0.06 were determined at [OL] = 0.075 and 1.47 M, respectively. The inverse value is determined under conditions where the the first step of the reaction dominates and is analyzed in terms of a rate-limiting attack of OL.Key words: formamide, activation parameters, water reaction, acid and base hydrolysis, solvent kinetic isotope effect.
An ab initio investigation of scandium chloro complexes
Authors: Pye Cory C , Corbeil Christopher R
Published: November 2002

A series of geometry, frequency, and energy calculations of chloroaquascandium(III) complexes were carried out at up to the MP2/6-31+G* level. A thorough examination of all species up to and including hexacoordinate species, and with up to six chlorides, was carried out. The structures of the complexes are compared with experimental data where available. The solution chemistry of scandium(III) in the presence of chloride is discussed.Key words: scandium, aqua complexes, chloro complexes, ab initio.
Reactions of 1,3-dipolar aldazines and ketazines with the dipolarophile dimethyl acetylenedicarboxylate
Authors: El-Alali Abdullah , Al-Kamali Ahmed S
Published: November 2002

The prepared aldazines (aldehyde azines) and ketazines (ketone azines) were allowed to react with 2 mol of the acetylene derivative. The first products formed were pentalene azine derivatives, which in some cases underwent skeletal rearrangment into acyclic tetraene azines. The latter underwent, in the case of some aldazine products, further skeletal rearrangment into N-allyl pyrazoles. The occurence of these rearrangments is dependant on the nature of the aldehydes or ketones used.Key words: dimethyl acetylenedicarboxylate (DMAD), aldazines, ketazines, N-allyl pyrazoles.
One-pot sequential PausonKhand reaction  transfer hydrogenation
Authors: Hätzelt André , Laschat Sabine
Published: November 2002

The PausonKhand reaction of norbornene (1) and phenylacetylene (2) and subsequent RuCl2(PPh3)3-catalyzed transfer hydrogenation of the resulting enone (3) can be carried out in a one-pot sequence if the base is added after an induction period. The desired ketones (4a, 4b) were obtained in good yield as a mixture of diastereomers (diastereomeric ratio (dr.) 58:42). The relative rates of both the Pauson-Khand reaction and the transfer hydrogenation are decreased by a factor of 2 in the sequence, as compared with the isolated reactions.Key words: PausonKhand reaction, transfer hydrogenation.
Radiolysis of liquid water: An attempt to reconcile Monte-Carlo calculations with new experimental hydrated electron yield data at early times
Authors: Muroya Yusa , Meesungnoen Jintana , Jay-Gerin Jean-Paul , Filali-Mouhim Abdelali , Goulet Thomas , Katsumura Yosuke , Mankhetkorn Samlee
Published: November 2002

A re-examination of our Monte-Carlo modeling of the radiolysis of liquid water by low linear-energy-transfer (LET ~ 0.3 keV µm1) radiation is undertaken herein in an attempt to reconcile the results of our simulation code with recently revised experimental hydrated electron (eaq) yield data at early times. The thermalization distance of subexcitation electrons, the recombination cross section of the electrons with their water parent cations prior to thermalization, and the branching ratios of the different competing mechanisms in the dissociative decay of vibrationally excited states of water molecules were taken as adjustable parameters in our simulations. Using a global-fit procedure, we have been unable to find a set of values for those parameters to simultaneously reproduce (i) the revised eaq yield of 4.0 ± 0.2 molecules per 100 eV at "time zero" (that is, a reduction of ~20% over the hitherto accepted value of 4.8 molecules per 100 eV), (ii) the newly measured eaq decay kinetic profile from 100 ps to 10 ns, and (iii) the time-dependent yields of the other radiolytic species H, OH, H2, and H2O2 (up to ~1 µs). The lowest possible limiting "time-zero" yield of eaq that we could in fact obtain, while ensuring an acceptable agreement between all computed and experimental yields, was ~4.4 to 4.5 molecules per 100 eV. Under these conditions, the mean values of the electron thermalization distance and of the geminate electroncation recombination probability, averaged over the subexcitation electron "entry spectrum," are found to be equal to ~139 Å and ~18%, respectively. These values are to be compared with those obtained in our previous simulations of liquid water radiolysis, namely ~88 Å and ~5.5%, respectively. Our average electron thermalization distance is also to be compared with the typical size (~6480 Å) of the initial hydrated electron distributions estimated in current deterministic models of "spur" chemistry. Finally, our average probability for geminate electroncation recombination agrees well with an estimated value of ~15% recently reported in the literature. In conclusion, this work shows that an adaptation of our calculations to a lower hydrated electron yield at early times is possible, but also suggests that the topic is not closed. Further measurements of the eaq yields at very short times are needed. Key words: liquid water, radiolysis, electroncation geminate recombination, electron thermalization distance, hydrated electron (eaq), eaq decay kinetics, time-dependent molecular and radical yields, Monte-Carlo simulations.
Alkoxide-functionalized cyclopentadienyl complexes of yttrium containing a two-carbon tether
Authors: Gendron Roland AL , Berg David J , Barclay Tosha
Published: November 2002

The ligand C5H4(CH2CH2CArF2OH) (3) (ArF = 3,5-C6H3(CF3)2) was prepared in two steps, from the iodo ester ICH2CH2CO2Me by way of the cyclopentadienyl ester C5H5CH2CH2CO2Me (2), in 55% overall yield. Thermal reaction of 3 with {Y[N(SiMe3)2]2(THF)2(µ-Cl)}2 afforded the neutral chloride complex {η5:η1-C5H4[CH2CH2C(O)(3,5-C6H3(CF3)2)2]}YCl{THF}n (5a: n = 2, 5b: n = 1). Metathesis reactions of 5 with 1 equiv of NaN(SiMe3)2, LiO-2,6-t-Bu2C6H3, and LiCH(SiMe3)2 afforded {η5:η1-C5H4[CH2CH2C(O)(3,5-C6H3(CF3)2)2]}Y{N(SiMe3)2}{THF}n (6), {η5:η1-C5H4[CH2CH2C(O)(3,5-C6H3(CF3)2)2]}Y{O-2,6-t-Bu2C6H3}{THF}n (7), and {η5:η1-C5H4[CH2CH2C(O)(3,5-C6H3(CF3)2)2]}Y{CH(SiMe3)2}{THF}n (8), respectively, (a: n = 2, b: n = 1). Exposure of the bis(THF) solvates to reduced pressure resulted in desolvation to the mono(THF) adducts for 58. The solid state structure of 6b was established by X-ray crystallography. In addition, formation of a spirocyclic ether (C4H6CH2CH2C(O)(3,5-C6H3(CF3)2)2 4), obtained by the intramolecular cyclization of ligand 3, was confirmed by X-ray crystallography. Key words: yttrium, organometallic, cyclopentadienyl, X-ray, alkoxide, chelate, alkyl, hybrid ligand, NMR, cyclization.
Structural and conformational studies of 5-(1H-pyrrol-2-ylmethylene)-substituted imidazolidine-2,4-diones and thiazolidine-2,4-diones
Authors: Dios Alfonso de , de la Puente Maria Luz , Rivera-Sagredo Alfonso , Espinosa Juan Felix
Published: November 2002

Some imidazolidine-2,4-dione (hydantoin) and thiazolidine-2,4-dione (TZD) derivatives with a 1H-pyrrol-2-ylmethylene substituent at the 5-position (18) have been synthesized via an aldol condensation reaction. A mixture of Z- and E- stereoisomers was obtained, as confirmed by HPLC and NMR studies. Assignment of the stereochemistry was achieved through chemical shift knowledge, NOE, and 3JH,C data. The conformation of the molecules depends on the configuration at the double bond. While the (NH,C cis) form is the most stable conformer for the E-isomer, the (NH,C trans) form is the preferred conformer for the Z-isomer. The temperature coefficients of the NH pyrrole protons reveal the existence of an intramolecular hydrogen bond for the E-isomers.Key words: hydantoin, TZD, NMR spectroscopy, conformational analysis, temperature coefficient.
L'échelle pKHBde basicité de liaison hydrogène des amines tertiaires aliphatiques
Authors: Graton Jérôme , Besseau François , Berthelot Michel , Raczynska Ewa D , Laurence Christian
Published: November 2002

The hydrogen bond acceptor strength of 40 tertiary amines has been measured by Fourier transform  infrared (FTIR) spectrometry from their 1:1 complexation constant towards 4-fluorophenol in CCl4at 25°C (the pKHBscale). Also measured was the frequency shift, Δν(OH), of the ν(OH) band of methanol hydrogen-bonded to these amines. The comparison of the thermodynamic hydrogen bond basicity scale, pKHB, with the spectroscopic one, Δν(OH), and with the Brønsted pKascale, points to the great sensitivity of pKHBto steric effects. The pKHBscale of tertiary amines extends from 2.71 for quinuclidine to 0.34 for N,N-diisopropyl-3-pentylamine. The main factors governing this important variation (17 kJ·mol1on the Gibbs energy scale) are the electron-withdrawing inductive effect and various kinds of steric effects (e.g., opening of the CNC angles and hindrance to OH fixation on the nitrogen lone pair). Infrared (IR) spectra show the attachment of 4-fluorophenol to the nitrile nitrogen of Me2NCH2C[Formula: see text]N and Me2NCH2CH2C[Formula: see text]N, to the oxygen of N-methylmorpholine, and to the π electrons of (HC[Formula: see text]CCH2)3N and (PhCH2)3N, in addition to the attachment to the amino nitrogen. In (PhCH2)3N, the electron-withdrawing effect of the three benzyl substituents and, mainly, the very important congestion of the nitrogen lone pair reduce the nitrogen hydrogen-bond basicity almost to nothing, so that tribenzylamine, a nitrogen Brønsted base, turns to a π base in hydrogen bonding. From this example, the large differences between the pKHBand pKascales of organic bases are emphasized.Key words: basicity, hydrogen bonding, tertiary amines, pKHBscale.
Synthesis of heteronuclear bifunctional Lewis acids by transmetalation of 1,8-bis(trimethylstannyl)naphthalene with BCl3
Authors: Schulte Marcus , Gabbaï François P
Published: November 2002

Reaction of 1,8-bis(trimethylstannyl)naphthalene (1) with an excess of BCl3 at 78°, followed by warming to 0°C, results in the exclusive formation of the novel bifunctional Lewis acid 1-(chlorodimethylstannyl)-8-(dichloroboryl)naphthalene (2), a compound in which a boryl and a stannyl moiety coexist at the peri-positions of a naphthalene core. At elevated temperature compound 2 undergoes a chloridemethyl exchange, which affords 1-(dichloromethylstannyl)-8-(chloromethylboryl)naphthalene (3). Compounds 2 and 3 have been characterized by multi-nuclear NMR spectroscopy. The single crystal X-ray analysis for compound 3 reveals a sterically crowded structure with an essentially trigonal planar boron center, and a tin center pentacoordinated in a [4+1]-fashion. Upon exposure to traces of water, compound 3 is converted into the borinic acid derivative 1-(dichloromethylstannyl)-8-(hydroxymethylboryl)naphthalene (4), which has been characterized by multi-nuclear NMR spectroscopy and single crystal X-ray analysis.Key words: multidentate Lewis acids, organoboranes, organostannanes.
Ambulatory Electrocardiographic Evidence of Transmural Dispersion of Repolarization in Patients With Long-QT Syndrome Type 1 and 2
Authors: Viitasalo Matti , Oikarinen Lasse , Swan Heikki , Väänänen Heikki , Glatter Kathy , Laitinen Päivi J. , Kontula Kimmo , Barron Hal V. , Toivonen Lauri , Scheinman Melvin M.
Published: November 2002

Background—

Transmural dispersion of repolarization (TDR) may be related to the genesis of torsade de pointes (TdP) in patients with the long-QT (LQT) syndrome. Experimentally, LQT2 models show increased TDR compared with LQT1, and β-adrenergic stimulation increases TDR in both models. Clinically, LQT1 patients experience symptoms at elevated heart rates, but LQT2 patients do so at lower rates. The interval from T-wave peak to T-wave end (TPE interval) is the clinical counterpart of TDR. We explored the relationship of TPE interval to heart rate and to the presence of symptoms in patients with LQT1 and LQT2.

Methods and Results—

We reviewed Holter recordings from 90 genotyped subjects, 31 with LQT1, 28 with LQT2, and 31 from unaffected family members, to record TPE intervals by use of an automated computerized program. The median TPE interval was greater in LQT2 (112±5 ms) than LQT1 (91±2 ms) or unaffected (86±3 ms) patients (
P
<0.001 for all group comparisons), and the maximal TPE values differed as well. LQT1 patients showed abrupt increases in TPE values at RR intervals from 600 to 900 ms, but LQT2 patients did so at RR intervals from 600 to 1400 ms (longest RR studied). Asymptomatic and symptomatic patients showed similar TDRs.

Conclusions—

TDR is greater in LQT2 than in LQT1 patients. LQT1 patients showed a capacity to increase TDR at elevated heart rates, but LQT2 patients did so at a much wider rate range. The magnitude of TDR is not related to a history of TdP.
Paradoxical Effect of Sibutramine on Autonomic Cardiovascular Regulation
Authors: Birkenfeld Andreas L. , Schroeder Christoph , Boschmann Michael , Tank Jens , Franke Gabi , Luft Friedrich C. , Biaggioni Italo , Sharma Arya M. , Jordan Jens
Published: November 2002

Background—

Sibutramine, a serotonin and norepinephrine transporter blocker, is widely used as an adjunctive obesity treatment. Norepinephrine reuptake inhibition with sibutramine conceivably could exacerbate arterial hypertension and promote cardiovascular disease.

Methods and Results—

In 11 healthy subjects (7 men, age 27±2 years, body mass index 23.1±0.7 kg/m
2
), we compared the effect of sibutramine or matching placebo (ingested 26, 14, and 2 hours before testing) on cardiovascular responses to autonomic reflex tests and to a graded head-up tilt test. In addition, we tested sibutramine in combination with metoprolol. Testing was conducted in a double-blind and crossover fashion. Supine systolic blood pressure was 113±3 mm Hg with placebo, 121±3 mm Hg with sibutramine (
P
<0.001 versus placebo), and 111±2 mm Hg with the combination of sibutramine and metoprolol. Similarly, sibutramine increased upright blood pressure. Sibutramine substantially increased upright heart rate. This effect was abolished with metoprolol. The blood pressure response to cold pressor and handgrip testing was attenuated with sibutramine compared with placebo. Furthermore, sibutramine decreased low-frequency oscillations of blood pressure and plasma norepinephrine concentrations in the supine position.

Conclusions—

The cardiovascular effect of the antiobesity drug sibutramine results from a complex interaction of peripheral and central nervous system effects. The inhibitory clonidine-like action of sibutramine on the central nervous system attenuates the peripheral stimulatory effect. Our findings strongly suggest that current concepts regarding the action of sibutramine on the sympathetic nervous system should be reconsidered.
Elevated Numbers of Tissue-Factor Exposing Microparticles Correlate With Components of the Metabolic Syndrome in Uncomplicated Type 2 Diabetes Mellitus
Authors: Diamant Michaela , Nieuwland Rienk , Pablo Renée F. , Sturk Augueste , Smit Jan W.A. , Radder Jasper K.
Published: November 2002

Background—

Type 2 diabetes is associated with accelerated atherosclerosis. Because cell-derived microparticles support coagulation and inflammation, they may be involved in atherogenesis. We characterized circulating microparticles both in patients with uncomplicated, well-regulated type 2 diabetes and in healthy subjects, as well as their relationship with coagulation and metabolic control.

Methods and Results—

Microparticles were isolated from plasma, stained with annexin V, cell-specific monoclonal antibodies (MoAbs) and a MoAb directed against tissue factor (TF), and analyzed by flow cytometry. Microparticle numbers and origin were comparable in the two groups, but the median number of TF-positive microparticles was twice as high in patients than in controls (
P
=0.018). Patients had higher percentages of TF-positive microparticles from T-helper cells (
P
=0.045), granulocytes (
P
=0.004), and platelets (
P
=0.002). Subpopulations of TF-positive microparticles from platelets and T-helper cells exposed granulocytic markers. Correlations were found between the numbers of various TF-positive microparticle subpopulations and body mass index, fasting plasma glucose and insulin, or tumor necrosis factor-α and serum HDL cholesterol. Microparticles from patients generated less thrombin in vitro (
P
=0.007). Microparticle numbers did not correlate with in vivo coagulation markers prothrombin fragment F
1+2
and thrombin-antithrombin complexes.

Conclusions—

TF, possibly of granulocytic origin, is exposed on microparticle subpopulations in asymptomatic patients with well-regulated type 2 diabetes. TF-positive microparticles are associated with components of the metabolic syndrome but not with coagulation. Thus, TF on microparticles may be involved in processes other than coagulation, including transcellular signaling or angiogenesis.
Maturation-Dependent Acquired Coronary Structural Alterations and Atherogenesis in the Dahl Sodium-Sensitive Hypertensive Rat
Authors: Kiefer Charles R. , McKenney James B. , Trainor Jane F. , Snyder L. Michael
Published: November 2002

Background—

The Dahl sodium-sensitive hypertensive rat exhibits atherogenic lesions after the initiation of a high-sodium/high-fat diet. This study was designed to gauge the effect of a preadolescent high-fat diet on the postadolescent rate of atherogenesis after supplementation of the diet with sodium.

Methods and Results—

Fifty-three Dahl S male rats were assigned to 2 dietary groups for the postweaning to early adolescence period (3 to 12 weeks): 29 to a standard diet (low-fat/low-sodium) and 24 to a high-fat/low-sodium diet. At age 9 weeks (just after puberty), animals from the high-fat group exhibited a relatively diminished density of coronary elastic fibers. There was no evidence of either lipid or monocytic infiltration of the subendothelial space. At age 12 weeks, most or all of the remaining animals in both groups were switched to a high-sodium/high-fat diet and were sampled through the following 8 weeks for the appearance of arterial lipid. After the switch, the high-fat–conditioned animals developed more extensive atherosclerotic pathological lesions more rapidly than their prepubertal standard-diet counterparts. The importance of the animal’s stage of maturation in this effect was underscored by the observation that delaying onset of the high-fat diet to early adolescence resulted in no ultimate difference from the pubertal controls in elastic fiber density.

Conclusions—

The maturation-dependent high-fat conditioning of these postweanling rats correlated with an accelerated rate of atherogenesis on the initiation of the high-sodium/high-fat diet, possibly as a direct result of an alteration in arterial elasticity.
Potential Role of Autoantibodies Belonging to the Immunoglobulin G-3 Subclass in Cardiac Dysfunction Among Patients With Dilated Cardiomyopathy
Authors: Staudt Alexander , Böhm Marko , Knebel Fabian , Grosse Yvonne , Bischoff Claudia , Hummel Astrid , Dahm Johannes B. , Borges Adrian , Jochmann Nicoline , Wernecke Klaus D. , Wallukat Gerd , Baumann Gert , Felix Stephan B.
Published: November 2002

Background—

Immunoadsorption capable of removing circulating autoantibodies represents an additional therapeutic approach in dilated cardiomyopathy (DCM). The role played by autoantibodies belonging to the immunoglobulin (Ig) subclass G-3 in cardiac dysfunction remains to be elucidated.

Methods and Results—

Patients with DCM (left ventricular ejection fraction <30%) participated in this case-control study. Nine patients underwent immunoadsorption with protein A (low affinity to IgG-3), and 9 patients were treated with anti-IgG, which removes all IgG subclasses. Immunoadsorption was performed in 4 courses at 1-month intervals until month 3. In the 2 groups, immunoadsorption induced comparable reduction of total IgG (>80%). IgG-3 was effectively eliminated only by anti-IgG adsorption (eg, during the first immunoadsorption course; protein A, −37±4%; anti-IgG, −89±3%;
P
<0.001 versus protein A). The β
1
-receptor autoantibody was effectively reduced only by anti-IgG (
P
<0.01 versus protein A). Hemodynamics did not change in the protein A group. In the anti-IgG group during the first immunoadsorption course, cardiac index increased from 2.3±0.1 to 3.0±0.1 L · min
−1
· m
−2
(
P
<0.01 versus protein A). After 3 months, before the last immunoadsorption course, cardiac index was 2.2±0.1 L · min
−1
· m
−2
in the protein A group and 3.0±0.2 L · min
−1
· m
−2
in the anti-IgG group (
P
<0.01 versus protein A). Left ventricular ejection fraction increased only in the anti-IgG group (
P
<0.05 versus protein A).

Conclusions—

Autoantibodies belonging to IgG-3 may play an important role in cardiac dysfunction of DCM. The removal of antibodies of the IgG-3 subclass may represent an essential mechanism of immunoadsorption in DCM.
Effects of Valsartan on Circulating Brain Natriuretic Peptide and Norepinephrine in Symptomatic Chronic Heart Failure
Authors: Latini Roberto , Masson Serge , Anand Inder , Judd Dianne , Maggioni Aldo P. , Chiang Yann-Tong , Bevilacqua Maurizio , Salio Monica , Cardano Paola , Dunselman Peter H.J.M. , Holwerda Nicolaas J. , Tognoni Gianni , Cohn Jay N.
Published: November 2002

Background—

Brain natriuretic peptide (BNP) and norepinephrine (NE) are strongly related to severity of and are independent predictors of outcome in heart failure. The long-term effects of angiotensin receptor blockers on BNP and NE in heart failure patients are not known.

Methods and Results—

Both BNP and NE were measured in 4284 patients randomized to valsartan or placebo in the Valsartan Heart Failure Trial (Val-HeFT) at baseline and 4, 12, and 24 months after randomization. The effects of valsartan were tested by ANCOVA, controlling for baseline values and concomitant ACE inhibitors and/or β-blockers. BNP and NE concentrations were similar at baseline in the 2 groups and were decreased by valsartan starting at 4 months and up to 24 months. BNP increased over time in the placebo group. At the end point, least-squares mean (±SEM) BNP increased from baseline by 23±5 pg/mL in the placebo group (n=1979) but decreased by 21±5 pg/mL (n=1940) in the valsartan group (
P
<0.0001). NE increased by 41±6 pg/mL (n=1979) and 12±6 pg/mL (n=1941) for placebo and valsartan, respectively (
P
=0.0003). Concomitant therapy with both ACE inhibitors and β-blockers significantly reduced the effect of valsartan on BNP but not on NE (
P
for interaction=0.0223 and 0.2289, respectively).

Conclusions—

In Val-HeFT, the largest neurohormone study in patients with symptomatic chronic heart failure, BNP and NE rose over time in the placebo group. Valsartan caused sustained reduction in BNP and attenuated the increase in NE over the course of the study. These neurohormone effects of valsartan are consistent with the clinical benefits reported in Val-HeFT.
Reduced Progression of Early Carotid Atherosclerosis After Antibiotic Treatment and
Chlamydia pneumoniae
Seropositivity
Authors: Sander Dirk , Winbeck Kerstin , Klingelhöfer Jürgen , Etgen Thorleif , Conrad Bastian
Published: November 2002

Background—

Chlamydia pneumoniae
(Cp) infection has been associated with atherosclerosis, and a beneficial effect of antibiotic therapy on future cardiovascular events was described.

Methods and Results—

We evaluated the effect of roxithromycin therapy (150 mg twice daily for 30 days) on the progression of the intima-to-media thickness (IMT) of the common carotid artery using duplex ultrasonography in a prospective and randomized trial with a follow-up of 2 years in 272 consecutive patients with ischemic stroke aged over 55 years in whom the first IMT measurement and Cp testing (IgG and IgA) were performed at least 3 years before the roxithromycin treatment. Cp IgG antibodies (≥1:64) were initially found in 123 (45%) patients and IgA antibodies (≥1:16) in 112 (41%) patients. During the 3 years before antibiotic therapy, Cp-positive patients showed an enhanced IMT progression, even after adjustment for other cardiovascular risk factors (0.12 [95% CI, 0.11 to 0.14] versus 0.07 [0.05 to 0.09] mm/year;
P
<0.005). The 62 Cp-positive patients given roxithromycin showed a significantly decreased IMT progression after 2 years compared with the Cp-positive patients without therapy (0.07 [0.045 to 0.095] versus 0.11 [0.088 to 0.132] mm/year;
P
<0.01). No significant difference in the occurrence of future cardiovascular events was found between both groups during follow-up. No change of IMT was observed in Cp-negative patients given roxithromycin (n=74) compared with those without therapy (0.06 [0.03 to 0.09] versus 0.07 [0.05 to 0.09] mm/year).

Conclusions—

Our findings suggest a positive impact of antibiotic therapy on early atherosclerosis progression in Cp-seropositive patients with cerebrovascular disease.
β
2
Integrin-Dependent Neutrophil Adhesion Induced by Minimally Modified Low-Density Lipoproteins Is Mainly Mediated by F
2
-Isoprostanes
Authors: Fontana Luigi , Giagulli Cinzia , Cominacini Luciano , Pasini Anna Fratta , Minuz Pietro , Lechi Alessandro , Sala Angelo , Laudanna Carlo
Published: November 2002

Background—

Oxidation of LDL produces a series of biologically active, oxidized lipids. Among them, isoprostanes, and in particular iPF
2α
-III, seem to be crucial in mediating some of the key cellular events seen in myocardial ischemia-reperfusion injury.

Methods and Results—

Minimally modified LDL (MM-LDL) triggers a dose-dependent, very rapid neutrophil adhesion to human fibrinogen. Rapid adhesion triggering correlates with degree of LDL oxidation and accumulation of isoprostanes. Isoprostanes accumulated in MM-LDL are major determinants of the proadhesive effect of oxidized LDL, as shown by experiments of receptor functional deletion. Moreover, evidence is provided of expression on human neutrophils of a biological active isoprostane receptor distinct from the classical thromboxane A
2
receptor.

Conclusions—

These data suggest that isoprostanes are major contributors to the proadhesive effect induced by MM-LDL on neutrophils and provide additional evidence for the involvement of isoprostanes in the pathogenesis of myocardial ischemia/reperfusion injury.
Relation of Ejection Fraction and Inducible Ventricular Tachycardia to Mode of Death in Patients With Coronary Artery Disease
Authors: Buxton Alfred E. , Lee Kerry L. , Hafley Gail E. , Wyse D. George , Fisher John D. , Lehmann Michael H. , Pires Luis A. , Gold Michael R. , Packer Douglas L. , Josephson Mark E. , Prystowsky Eric N. , Talajic Mario R.
Published: November 2002

Background—

Fifty percent of deaths in patients with coronary disease occur suddenly. Although many factors correlate with increased mortality, there is little information regarding the influence of these factors on mode of death. As such, optimum methods to determine patients most likely to benefit from implantable defibrillator therapy are unclear.

Methods and Results—

We analyzed the relation of ejection fraction and inducible ventricular tachyarrhythmias to mode of death in all 1791 patients enrolled in the Multicenter Unsustained Tachycardia Trial who did not receive antiarrhythmic therapy. Total mortality and arrhythmic deaths/cardiac arrests occurred more frequently in patients with ejection fraction <30% than in those with ejection fraction of 30% to 40%. The percentage of deaths classified as arrhythmic was similar in patients with ejection fraction <30% or ≥30%. The relative contribution of arrhythmic events to total mortality was significantly higher in patients with inducible tachyarrhythmia (58% of deaths in inducible patients versus 46% in noninducible patients,
P
=0.004). The higher percentage of events that were arrhythmic among patients with inducible tachyarrhythmia appeared more distinct among patients with an ejection fraction ≥30% (61% of events were arrhythmic among inducible patients with ejection fraction ≥30% and only 42% among noninducible patients,
P
=0.002).

Conclusions—

Both low ejection fraction and inducible tachyarrhythmias identify patients with coronary disease at increased mortality risk. Ejection fraction does not discriminate between modes of death, whereas inducible tachyarrhythmia identifies patients for whom death, if it occurs, is significantly more likely to be arrhythmic, especially if ejection fraction is ≥30%.
Perivascular Superoxide Anion Contributes to Impairment of Endothelium-Dependent Relaxation
Authors: Rey Federico E. , Li Xiao-Chun , Carretero Oscar A. , Garvin Jeffrey L. , Pagano Patrick J.
Published: November 2002

Background—

Like endothelial and smooth muscle cells, vascular adventitial fibroblasts contain a substantial NAD(P)H oxidase superoxide anion (O
2
−
)-generating system activated by angiotensin II (Ang II). Based on the ability of nitric oxide (NO·) to diffuse rapidly through tissue and the fast reaction rate of NO· and O
2
−
, we postulated that the interaction between NO· and adventitial NAD(P)H oxidase–derived O
2
−
contributes to impairment of endothelium-dependent relaxation (EDR).

Methods and Results—

C57Bl/6 mouse abdominal aortas were simultaneously perfused intraluminally and suffused adventitially with physiological buffer at 37°C. After constricting the vessels with phenylephrine, an acetylcholine dose-response curve was obtained while monitoring changes in diameter by videomicroscopy. Endogenous O
2
−
was increased by treating the adventitial side of the aortas with Ang II (10 pmol/L), leading to impairment of EDR. EDR impairment was reversed by adventitial suffusion of superoxide dismutase (SOD) of aortas from wild-type mice. Ang II–treated aortas from gp91

phox
−/−

mice, which lack significant adventitial O
2
−
, exhibited greater EDR and were not affected by SOD. Adventitially suffused SOD failed to penetrate the media, indicating that the effects of SOD were localized to the adventitia. Adventitial application of the O
2
−
-generating system xanthine/xanthine oxidase or the potent NO scavenger oxyhemoglobin impaired EDR.

Conclusions—

O
2
−
derived from adventitial gp91

phox

-based NAD(P)H oxidase contributes to impairment of the action of endothelium-derived NO·.
Interaction between wear processes and limit cycle oscillations of a control surface with free-play non-linearity
Authors: Safi S A , Kelly D W , Archer R D
Published: November 2002

This paper provides a detailed study of a non-linear aeroelastic phenomenon first addressed by Safi et al., i.e. coupling a model for wear in mechanical linkages to the aeroelastic response of a non-linear wing—aileron or stabilizer—elevator system. The aeroelastic behaviour of these systems with free-play structural non-linearity in the control surface restoring moment is examined. The underlying dynamics and deterioration of the system due to ageing are investigated. Extensive numerical simulations are performed using Wagner' function to evaluate the aerodynamic forces. The resulting equations are integrated numerically to give time histories of the airfoil—aileron motion. Regions of limit cycle oscillations (LCOs) and chaotic vibration are identified well below the linear flutter speed. Finally qualitative and quantitative wear analyses are presented to provide relationships to predict the depth of wear in the mechanical connections experiencing LCOs. The problem is shown to be coupled with an accelerating wear rate as the free play develops.
Modelling and Analysing Impacts of Wind Power on Transient Stability of Power Systems
Authors: Slootweg J.G. , Kling W.L.
Published: November 2002

This paper considers the impact of increasingly large numbers of wind turbine generators on the stability of power grid networks. Most modern wind turbines do not have conventional grid coupled synchronous generators, as is the case with most other technologies for electrical power generation. Instead, squirrel cage induction generators are used, or generators that are grid coupled with power electronic converters. Consequently, wind turbines interact with the power system in a way that differs from conventional generators. In the paper, the interaction between wind turbines and the power system is investigated using simulations of a widely used representative dynamics test system in which a high wind power penetration is assumed. It is concluded that the impact of wind power on power system transient stability varies much when either constant or variable speed wind turbines are used.
Local Wind Climate within and Downwind of Large Offshore Wind Turbine Clusters
Authors: Frandsen Sten , Barthelmie Rebecca
Published: November 2002

This Note reviews presentations made at a meeting for experts, held at the Risø Laboratory, concerning possible approaches to improving understanding of local wind climates within large offshore wind farms and particularly their impact on downwind wind farms. Such effects are detectable both within and beyond the boundaries of each windfarm, which typically has 10 to 100 large turbines of rotor diameter up to 80 m and hub-heights between 60 and 80 m.
Influence of nonspecific brain and plasma binding on CNS exposure: implications for rational drug discovery
Authors: Cory Kalvass J. , Maurer Tristan S.
Published: November 2002

Relative plasma, brain and cerebrospinal fluid (CSF) exposures and unbound fractions in plasma and brain were examined for 18 proprietary compounds in rats. The relationship between in vivo brain‐to‐plasma ratio and in vitro plasma‐to‐brain unbound fraction (fu) was examined. In addition, plasma fu and brain fu were examined for their relationship to in vivo CSF‐to‐plasma and CSF‐to‐brain ratios, respectively. Findings were delineated based on the presence or absence of active efflux. Finally, the same comparisons were examined in FVB vs. MDR 1a/1b knockout mice for a selected P‐glycoprotein (Pgp) substrate. For the nine compounds without indications of active efflux, predictive correlations were observed between ratios of brain‐to‐plasma exposure and plasma‐to‐brain fu (r2 = 0.98), CSF‐to‐brain exposure vs. brain fu (r2 = 0.72), and CSF‐to‐plasma exposure vs. plasma fu (r2 = 0.82). For the nine compounds with indications of active efflux, nonspecific binding data tended to over predict the brain‐to‐plasma and CSF‐to‐plasma exposure ratios. Interestingly, CSF‐to‐brain exposure ratio was consistently under predicted by brain fu for this set. Using a select Pgp substrate, it was demonstrated that the brain‐to‐plasma exposure ratio was identical to that predicted by plasma‐to‐brain fu ratio in MDR 1a/1b knockout mice. In FVB mice, plasma‐to‐brain fu over predicted brain‐to‐plasma exposure ratio to the same degree as the difference in brain‐to‐plasma exposure ratio between MDR 1a/1b and FVB mice. Consistent results were obtained in rats, suggesting a similar kinetic behavior between species. These data illustrate how an understanding of relative tissue binding (plasma, brain) can allow for a quantitative examination of active processes that determine CNS exposure. The general applicability of this approach offers advantages over species‐ and mechanism‐specific approaches. Copyright © 2002 John Wiley & Sons, Ltd.
Pharmacokinetics of SB‐247083, a potent and selective endothelinA receptor antagonist, in the rat, dog, and monkey
Authors: Ward Keith W. , Azzarano Leonard M. , Morgan Jayme A. , Gould Michael J. , Perng Cherng‐Yih , Souder Pamela R. , Lundberg David , Smith Brian R.
Published: November 2002

The endothelins (ET) are among the most potent vasoconstrictors identified to date, and have been implicated in such diseases as renal failure, pulmonary hypertension, atherosclerosis, and congestive heart failure. There is currently interest in developing selective antagonists of the ET‐A subtype receptor, and one such antagonist is SB‐247083 ((E)‐[1‐butyl‐5‐[2‐(2‐carboxyphenyl) methoxy‐4‐chlorophenyl]‐1H‐pyrazole‐4‐yl]‐2‐[5‐methoxydihydrobenzofuran‐6‐yl]methyl]‐2‐propionic acid). This investigation was conducted to evaluate the preclinical pharmacokinetics of SB‐247083. Clearance of SB‐247083 was low to moderate in the rat and monkey, and high in the dog. Oral bioavailability of SB‐247083 administered as a solid formulation of the free acid was 24% in the rat, but low in the dog (4%) and the monkey (2%). An extensive in vitro salt form and formulation screen resulted in the identification of a formulation containing the monoarginyl salt with improved dissolution properties. This formulation provided a 2‐ to 4‐fold increase in oral bioavailability in each of the preclinical species. In the dog, this improvement was reversed by the pre‐administration of 0.1 N HCl to normalize the achlorhydric fasting dog stomach. These data show that SB‐247083 may have suitable drug properties for progression in development. Copyright © 2002 John Wiley & Sons, Ltd.
CD157, the Janus of CD38 but with a unique personality
Authors: Ortolan Erika , Vacca Paola , Capobianco Andrea , Armando Enrico , Crivellin Federico , Horenstein Alberto , Malavasi Fabio
Published: November 2002

CD157 is a pleiotropic ectoenzyme which belongs to the CD38 family and to the growing number of leukocyte surface molecules known to act independently as both receptors and enzymes. A 45‐kDa surface structure with a GPI anchor, the CD157 molecule displays two distinct domains in its extracellular component. The first is implicated in the enzymic activities of the molecule and the second features adhesion/signalling properties. CD157 shares several characteristics with CD38, including a similar amino acid sequence and enzymic functions. Both molecules are involved in the metabolism of NAD+, and the CD157 gene is synthenic on 4p15 with CD38, with which it also shares a unique genomic organization. Their conservation in phylogeny is striking evidence for their relevance in the life and death cycle of the cell. Copyright © 2002 John Wiley & Sons, Ltd.
Agonists of proteinase‐activated receptor 2 induce TNF‐αsecretion from astrocytoma cells
Authors: Kim Mi‐Sun , Jo Hyun , Um Jae‐Young , Yi Jin‐Mu , Kim Dae‐Ki , Choi Suck‐Chei , Kim Tae‐Hyun , Nah Yong‐Ho , Kim Hyung‐Min , Lee Young‐Mi
Published: November 2002

Proteinase‐activated receptor 2 (PAR2) is cleaved and activated by trypsin or mast cell tryptase, and may play an important role in inflammation. We have investigated the potential of PAR2 agonists to modulate TNF‐α secretion from human astrocytoma cell line CCF‐STTG1. We found that CCF‐STTG1 expresses PAR2 by RT‐PCR and Western blot analysis. Agonists such as trypsin, the peptide SLIGKV‐NH2 (corresponding to the PAR2 tethered ligand), or mast cell tryptase directly signal to CCF‐STTG1 to stimulate secretion of TNF‐α but do not stimulate in the presence of soybean trypsin inhibitor (SBTI) or VKGILS‐NH2 (reverse peptide). The secretion of TNF‐α by trypsin was significantly blocked by pretreatment with either 50 μM PD98059 or 1 μM SB203580. Furthermore, trypsin stimulated the activation of extracellular signal‐regulated kinase (ERK) and p38 MAP kinase homologue in CCF‐STTG1 without any detectable activation of c‐Jun N‐terminal kinase (JNK). These results show that trypsin may induce TNF‐α secretion following activation of ERK and p38 via PAR2 in CCF‐STTG1. Copyright © 2002 John Wiley & Sons, Ltd.
Monitoring the response to rTMS in depression with visual analog scales
Authors: Grunhaus Leon , Dolberg Ornah T. , Polak Dana , Dannon Pinhas N.
Published: November 2002

Visual analog scales (VAS) administered on a daily basis provide a fast and reliable method for assessing clinical change during transcranial magnetic stimulation (TMS). We treated 40 patients with major depression with TMS and assessed their clinical condition with VAS. Response to TMS was defined with the Hamilton rating scale for depression and the Global assessment of function scale. Nineteen patients of 40 were responders to TMS (when the whole sample was considered) whereas 17 of 29 responded when only the non‐psychotic patients were considered. Patients who eventually responded to TMS demonstrated early changes in the VAS scores. We conclude that monitoring with VAS scores can detect early response to TMS. Copyright © 2002 John Wiley & Sons, Ltd.
Safety and efficacy of high dose of venlafaxine XL in treatment resistant major depression
Authors: Mbaya P.
Published: November 2002

Aim

The aim of the study was to look at efficacy and the safety profile of high dose (450–600 mg) venlafaxine XL in five patients with treatment resistant major depressive illness.

Methods

Five patients with treatment resistant depression were treated with high dose venlafaxine XL. Efficacy was evaluated using the Montgomery–Asberg depression rating scale (MADRS), the 21‐item Hamilton rating scale for depression (HAM‐D‐21) and the clinical global impressions (CGI) scale. Level of functioning was evaluated by social adaptation self‐evaluation scale (SASS). Body weight, supine pulse and blood pressure were recorded.

Results

The response rate was based on a 50% decrease in MADRS and HAM‐D scores between weeks 1 and 24. There was a more than 50% decrease in MADRS scores in 3 of 5 patients and 4 of 5 patients in HAM‐D scores. There was a trend to improvement of SASS scores in three of the study patients and in two of them the mean scores were within the normal range. Supine pulse and blood pressure remained stable in four patients, except in one patient where there was a slight increase although the final reading at week 24 was normal. Weight was relatively stable in all three patients where it was recorded, but in one patient there was a slight increase which may have been due to an atypical neuroleptic the patient was taking at the time.

Conclusion

High dose venlafaxine was safe, well tolerated and effective in this small number of severe treatment resistant patients with major depression and it also improved social functioning. Copyright © 2002 John Wiley & Sons, Ltd.