bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient new cationic liposome formulation for systemic delivery of small interfering RNA silencing tumor necrosis factor α in experimental arthritis
Authors: Khoury Maroun , Louis‐Plence Pascale , Escriou Virginie , Noel Danièle , Largeau Céline , Cantos Céline , Scherman Daniel , Jorgensen Christian , Apparailly Florence 
Published: May 2006

AbstractObjectiveTumor necrosis factor α (TNFα) is among the most prominent cytokines in rheumatoid arthritis (RA) and is secreted mainly by macrophages. A direct method for restoring the immunologic balance in RA is use of small interfering RNA (siRNA) for silencing the TNFα transcript. The aim of this study was to determine the therapeutic effect of systemic administration of TNFα siRNA in an experimental model of RA, optimizing its delivery using new liposome formulations.MethodsMurine macrophages were transfected with siRNA targeting TNFα, and expression was measured. The therapeutic effect in collagen‐induced arthritis (CIA) was assessed after intravenous delivery of TNFα siRNA. Delivery was optimized using a carrier DNA for complexation with the cationic liposome RPR209120/DOPE. Levels of TNFα and other cytokines were measured in sera and joint tissue–conditioned media. Biodistribution was determined using a fluorescent siRNA.ResultsIn vitro, TNFα siRNA efficiently and specifically modulated the expression of TNFα at both the messenger RNA and protein levels. In vivo, complete cure of CIA was observed when TNFα siRNA was administered weekly, complexed with the liposome and combined with carrier DNA. Inhibition (50–70%) of articular and systemic TNFα secretion was detected in the siRNA‐injected groups, which correlated with a decrease in the levels of interleukin‐6 and monocyte chemotactic protein 1. The main organs targeted by siRNA were the liver and spleen; the addition of liposome RPR209120 and carrier DNA significantly increased organ uptake.ConclusionWe demonstrated the efficiency of systemic delivery of siRNA designed to silence TNFα in CIA, using a liposome carrier system as a way to address the methodologic limitations in vivo.
Transdermal fentanyl for improvement of pain and functioning in osteoarthritis: A randomized, placebo‐controlled trial
Authors: Langford Richard , McKenna Frank , Ratcliffe Stuart , Vojtassák Jozef , Richarz Ute 
Published: May 2006

AbstractObjectiveAlthough common treatments for osteoarthritis (OA) pain, such as nonsteroidal antiinflammatory drugs (NSAIDs), simple analgesics, and weak opioids, provide relief in some cases, they fail to control pain or are poorly tolerated in many cases. Strong opioids have been used to successfully treat several types of noncancer pain but have rarely been tested in controlled studies. Therefore, we tested the effects of transdermal fentanyl (TDF) in patients with moderate‐to‐severe OA pain, in a placebo‐controlled study.MethodsThe cohort comprised patients with radiologically confirmed OA of the hip or knee (meeting the American College of Rheumatology criteria) requiring joint replacement and with moderate‐to‐severe pain that had been inadequately controlled by weak opioids. The patients were randomized to receive TDF or placebo for 6 weeks after a 1‐week pretreatment run‐in phase. During study treatment, previously prescribed NSAIDs and simple analgesics were continued, but weak opioids were discontinued. All patients had access to paracetamol and metoclopramide. Pain was recorded on a visual analog scale (VAS), and function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).ResultsData were available for 399 patients (202 receiving TDF, 197 receiving placebo), of whom 199 (50%) completed the study. TDF provided significantly better pain relief than placebo, as demonstrated by the primary outcome measure (area under the curve for VAS scores −20 in the TDF group versus −14.6 in the placebo group; P = 0.007). TDF was also associated with significantly better overall WOMAC scores and pain scores. The most common adverse events were nausea, vomiting, and somnolence, and these occurred more often in the TDF group.ConclusionTDF can reduce pain and improve function in patients with knee or hip OA.
Relationship of serum paraoxonase 1 activity and paraoxonase 1 genotype to risk of systemic lupus erythematosus
Authors: Tripi Laura M. , Manzi Susan , Chen Qi , Kenney Margaret , Shaw Penny , Kao Amy , Bontempo Franklin , Kammerer Candace , Kamboh M. Ilyas 
Published: May 2006

AbstractObjectiveLow serum paraoxonase 1 (PON1) activity determined with paraoxon as substrate has been found to be associated with coronary artery disease. This study was undertaken to examine the relationship of PON1 activity and genotype to risk of systemic lupus erythematosus (SLE).MethodsThe impact of 7 PON1 single‐nucleotide polymorphisms (SNPs) was analyzed in relation to PON1 activity, SLE risk, lupus nephritis, antiphospholipid antibody (aPL) positivity, and carotid vascular disease in 380 SLE patients (334 white, 46 black) and 497 controls (455 white, 42 black).ResultsCompared with findings in controls, PON1 activity with paraoxon substrate was reduced both in white lupus patients (mean ± SEM 618.9 ± 24.0 units/liter versus 719.6 ± 24.6 units/liter; P = 0.007) and in black lupus patients (991.1 ± 82.7 units/liter versus 1,164.3 ± 101.4 units/liter; P = 0.2711). Low PON1 activity in SLE was not associated with the occurrence of aPL, carotid vascular disease, or the use of immunosuppressive drugs. In multiple regression analyses, the Q192R SNP was found to be independently associated with PON1 activity and explained 28% and 41% of the variation in PON1 activity in white patients and black patients, respectively. Stratification of the lupus sample by presence (n = 81) or absence (n = 247) of renal disease revealed significant associations with 3 promoter SNPs, with odds ratios of 3.82 (95% confidence interval [95% CI] 1.49–9.82, P = 0.005), 3.41 (95% CI 1.35–8.61, P = 0.009), and 2.17 (95% CI 1.01–4.68, P = 0.049).ConclusionTo our knowledge, this is the first study to assess the role of PON1 activity in SLE risk in a large biracial sample from the US. Our data indicate that low PON1 activity determined with paraoxon substrate is independently associated with SLE and that certain PON1 SNPs are associated with lupus nephritis.
Noggin haploinsufficiency differentially affects tissue responses in destructive and remodeling arthritis
Authors: Lories Rik J. U. , Daans Melina , Derese Inge , Matthys Patrick , Kasran Ahmad , Tylzanowski Przemko , Ceuppens Jan L. , Luyten Frank P. 
Published: May 2006

AbstractObjectiveThe balance between destruction and homeostatic or reparative responses determines the outcome of arthritis. Increasing evidence suggests a role for signaling pathways, essential for development and growth, in the maintenance of tissue homeostasis and attempts at repair. Inappropriate activation of such pathways may also have a role in disease progression. We undertook this study to determine the effect of shifting the balance in bone morphogenetic protein (BMP) signaling in different mouse models of arthritis.MethodsEndogenous levels of noggin, a BMP antagonist, were reduced using heterozygous noggin+/LacZ mice in a model of inflammation‐driven destruction (methylated bovine serum albumin [mBSA]–induced monarthritis), a model of systemic autoimmune arthritis (collagen‐induced arthritis [CIA]), and a model of joint ankylosis (spontaneous arthritis in DBA/1 mice). In addition, we studied BMP inactivation by adenoviral noggin overexpression in destructive arthritis. Cartilage damage and activation of BMP signaling were studied by digital image analysis using Safranin O sulfated glycosaminoglycan staining and immunohistochemistry for phosphorylated Smads (Smads 1, 5, and 8), respectively.ResultsNoggin haploinsufficiency provided protection for articular cartilage against destruction in mBSA‐induced arthritis. Antagonist overexpression rendered cartilage more vulnerable in this model. Noggin gene transfer in knees affected by CIA also enhanced cartilage damage. Haploinsufficiency did not affect CIA, but noggin+/LacZ mice had an increased number of CD4‐positive cells with normal immune responses. In noggin+/LacZ DBA/1 mice with spontaneous arthritis, we observed delayed progression from cartilage to bone formation.ConclusionTight spatiotemporal control of BMP signaling appears to be critical in the response of joint tissues in models of arthritis.
Increase in circulating endothelial precursors by atorvastatin in patients with systemic sclerosis
Authors: Kuwana Masataka , Kaburaki Junichi , Okazaki Yuka , Yasuoka Hidekata , Kawakami Yutaka , Ikeda Yasuo 
Published: May 2006

AbstractObjectiveTo evaluate whether atorvastatin can increase bone marrow–derived circulating endothelial precursors (CEPs) and improve the vascular symptoms in patients with systemic sclerosis (SSc; scleroderma).MethodsThe study was designed as an open‐label, prospective study involving 14 patients with SSc who received 10 mg/day of atorvastatin for 12 weeks and were followed up for the subsequent 4 weeks. CEPs were quantified at weeks 0 (pretreatment), 4, 8, 12 (during treatment), and 16 (posttreatment) by cell sorting followed by 3‐color flow cytometry. Raynaud's phenomenon variables, global measures, and psychological scales as well as circulating angiogenic factors and endothelial activation/injury markers were serially assessed. The potential of CEPs to differentiate into mature endothelial cells was examined in cultures with angiogenic stimuli.ResultsNone of the patients experienced an adverse event, but 1 dropped out because of an excessive decrease in serum total cholesterol. Atorvastatin treatment resulted in a 1.7‐ to 8.0‐fold increase in CEPs from baseline levels (P < 0.0001), but the numbers returned to within baseline levels at posttreatment. However, 8 patients (62%) experienced a gradual decrease in the number of CEPs, even while taking atorvastatin. Variables indicating the extent of Raynaud's phenomenon improved significantly, and up‐regulated levels of angiogenic factors and vascular endothelial activation/injury markers decreased significantly during atorvastatin treatment. These variables returned to within baseline levels after discontinuation of the drug. In contrast, atorvastatin failed to improve the in vitro maturation potential of CEPs.ConclusionThe results of this pilot study suggest that atorvastatin treatment can increase CEPs and may be effective in improving Raynaud's phenomenon, even in SSc patients who have CEP dysfunction intrinsically.
Abnormal microvascular response is localized to the digits in patients with systemic sclerosis
Authors: Murray A. K. , Moore T. L. , King T. A. , Herrick A. L. 
Published: May 2006

AbstractObjectiveTo investigate the hypothesis that cutaneous microvascular perfusion of the dorsum of the hand (in response to local heating) and distal phalanx (in response to occlusion) is impaired in patients with systemic sclerosis (SSc) compared with healthy controls.MethodsTwenty‐nine patients with SSc and 29 control subjects were recruited. Perfusion was monitored using novel dual‐wavelength laser Doppler imaging, allowing measurement of both smaller (capillaries) and larger (thermoregulatory) vessels. Postacclimatization, a baseline dorsum scan (red or green wavelength) was performed. A heating pad was placed on the dorsum (total stimulus time 6 minutes at 34–40°C), and following removal of the pad, baseline wavelength scans were performed until perfusion returned to baseline values. This was then repeated for the second wavelength. The maximum perfusion increase due to heating (PEAK1) and area under the perfusion–time curve (AUC) were determined. In addition, scans (both wavelengths) of the index finger were performed prior to and during 2 minutes of suprasystolic occlusion, and the response upon occlusion release was monitored with single‐point laser Doppler. The decrease in perfusion due to occlusion (from preocclusion baseline values) (%DECREASE) and the maximum increase (from baseline perfusion values under occlusion) in hyperemic perfusion upon removal of occlusion (PEAK/OCC) were calculated.ResultsPEAK1 and AUC values were not significantly different between patients and controls, as assessed with either wavelength. A significant difference between groups was found in the %DECREASE values with the green, but not the red, wavelength. A significant between‐group difference was also found in PEAK/OCC values, using both wavelengths.ConclusionThis study suggests that SSc has no effect on microvascular perfusion in the dorsum of the hand, and that the abnormal microvascular response is localized to the digits, affecting both smaller and larger vessels.
Exposure to ELF magnetic and ELF‐modulated radiofrequency fields: The time course of physiological and cognitive effects observed in recent studies (2001–2005)
Authors: Cook C.M. , Saucier D.M. , Thomas A.W. , Prato F.S. 
Published: May 2006

AbstractIn 2002, we published a review of the cognitive and physiological effects of extremely low frequency magnetic fields (ELF MFs) and ELF‐modulated radiofrequency fields associated with mobile phones. Since the original preparation of that review, a significant number of studies have been published using techniques such as electroencephalography, event‐related potentials and positron emission tomography to investigate electromagnetic field effects upon human physiology and various measures of performance (cognitive, perceptual, behavioral). We review these recent studies, and when effects were observed, we reference the time course of observed effects (immediate or delayed). In our concluding remarks, we discuss a number of variables that are not often considered in human bioelectromagnetics studies, such as personality, individual differences and the specific laterality of ELF MF and mobile phone exposure over the brain. We also consider the sensitivity of various physiological assays and performance measures in the study of biological effects of electromagnetic fields. Bioelectromagnetics 27:613–627, 2006. © 2006 Wiley‐Liss, Inc.
Stress reducing regulative effects of integrated mental training with self‐hypnosis on the secretion of dehydroepiandrosterone sulfate (DHEA‐S) and cortisol in plasma: a pilot study
Authors: Johansson Benny , Uneståhl Lars‐Eric 
Published: May 2006

AbstractEarly observations have shown that preventive educational efforts towards experience of stress entail advantages in terms of improved well‐being, health and performance. We examined the influence in healthy subjects of self‐hypnosis and mental training taught in group sessions, with individual training in between according to a standard protocol, and integrated in daily life and work for six months, on the alteration in plasma concentration of the stress hormone cortisol and the ‘anti ageing’ hormone dehydroepiandrosterone sulfate (DHEA‐S). DHEA‐S and cortisol were analysed in twelve healthy men and women, with six individuals randomly divided equally between experimental and control groups. In the experimental group DHEA‐S was significantly increased by 16% (P < 0.05), whereas plasma DHEA‐S in controls followed an expected age‐related decline. Cortisol was reduced by 12.3% (P < 0.05) in the experimental group, but remained unchanged in the control group. The ratio between plasma concentrations of DHEA‐S and cortisol that reflects stress‐related alteration in the adrenal secretion between androgens and glucocorticoids, increased significantly by 27.8% (P < 0.05) in the experimental group with a reduction of 8,2% in controls. The increase in plasma DHEA‐S under experimental conditions was equivalent to a range normally found in individuals 5 to 10 years younger. Copyright © 2006 British Society of Experimental & Clinical Hypnosis. Published by John Wiley & Sons, Ltd.
Triplet MLCT Photosensitization of the Ring‐Closing Reaction of Diarylethenes by Design and Synthesis of a Photochromic Rhenium(I) Complex of a Diarylethene‐Containing 1,10‐Phenanthroline Ligand
Authors: Ko Chi‐Chiu , Kwok Wai‐Ming , Yam Vivian Wing‐Wah , Phillips David Lee 
Published: May 2006

AbstractSynthesis of the diarylethene‐containing ligand L1 based on Suzuki cross‐coupling reaction between thienyl boronic acid and the dibromophenanthroline ligand is reported. On coordination to the rhenium(I) tricarbonyl complex system, the photochromism of L1 could be photosensitized and consequently extended from intraligand excitation at λ≤340 nm in the free ligand to metal‐to‐ligand charge‐transfer (MLCT) excitation at λ≤480 nm in the complex. The photochromic reactions were studied by 1H NMR, UV/Vis, and steady‐state emission spectroscopy. Photosensitization was further probed by ultrafast transient absorption and time‐resolved emission spectroscopy. The results provided direct evidence that the formation of the closed form by the MLCT‐sensitized photochromic process was derived from the 3MLCT excited state. This supports the photosensitization mechanism, which involves an intramolecular energy‐transfer process from the 3MLCT to the 3IL(L1) state that initiated the ring‐closure reaction. The photophysical and electrochemical properties of the complex were also investigated.
The Reaction Mechanism of a Complex Intercalation System: In Situ X‐ray Diffraction Studies of the Chemical and Electrochemical Lithium Intercalation in Cr4TiSe8
Authors: Behrens Malte , Kiebach Ragnar , Ophey Jannes , Riemenschneider Oliver , Bensch Wolfgang 
Published: May 2006

AbstractThe intercalation reaction between Cr4TiSe8and Li was investigated from a kinetic and an electrochemical perspective. The structural phase transition from monoclinic to trigonal symmetry was probed by in situ energy‐dispersive X‐ray diffraction (in situ EDXRD) for chemical intercalation with butyllithium (BuLi). A change in the kinetic mechanism was detected for the reaction at room temperature; this was interpreted in terms of a trend from phase boundary control to diffusion control. A single diffusion‐controlled mechanism is obeyed at 60 °C. The electrochemical measurements and the corresponding in situ X‐ray diffraction (in situ XRD) data revealed that the monoclinic host is intercalated up to the composition Lix≈0.1Cr4TiSe8before the characteristic phase transition starts. The monoclinic phase undergoes complex structural changes in the following two‐phase regime. Owing to the co‐existence of two phases, the cell potential is constant for 0.1<x<0.7 and 0.9<x<3.0. The subsequent intercalation into the trigonal phase leads to a pronounced increase in the cell volume of the trigonal phase that stops atx≈0.8. At this point, the complete reduction of TiIVgives rise to a voltage drop of the cell potential. XANES measurements revealed that the reduction of TiIVoccurs prior to the reduction of CrIII.
Helically Chiral Ferrocene Peptides Containing 1′‐Aminoferrocene‐1‐Carboxylic Acid Subunits as Turn Inducers
Authors: Barišić Lidija , Čakić Mojca , Mahmoud Khaled A. , Liu You‐nian , Kraatz Heinz‐Bernhard , Pritzkow Hans , Kirin Srećko I. , Metzler‐Nolte Nils , Rapić Vladimir 
Published: May 2006

AbstractWe present a detailed structural study of peptide derivatives of 1′‐aminoferrocene‐1‐carboxylic acid (ferrocene amino acid, Fca), one of the simplest organometallic amino acids. Fca was incorporated into di‐ to pentapeptides withD‐ andL‐alanine residues attached to either the carboxy or amino group, or to both. Crystallographic and spectroscopic studies (circular dicroism (CD), IR, and NMR) of about two dozen compounds were used to gain a detailed insight into their structures in the solid state as well as in solution. Four derivatives were characterized by single‐crystal X‐ray analysis, namely Boc‐Fca‐Ala‐OMe (16), Boc‐Fca‐D‐Ala‐OMe (17), Boc‐Fca‐β‐Ala‐OMe (18), and Boc‐Ala‐Fca‐Ala‐Ala‐OMe (21) (Boc=tert‐butyloxycarbamyl). CD spectroscopy is an extremely useful tool to elucidate the helical chirality of the metallocene core. Unlike in all other known ferrocene peptides, the helical chirality of the ferrocene is governed solely by the chirality of the amino acid attached to the N terminus of Fca. Depending on the degree of substitution of both cyclopentadiene (Cp) rings, different hydrogen‐bonding patterns are realized.1H NMR and IR spectroscopy, together with the results from X‐ray crystallography, give detailed information regarding not only the hydrogen‐bonding patterns of the compounds, but also the equilibria between different conformers in solution. Differences in chemical shifts of NH protons in dimethyl sulfoxide ([D6]DMSO) and CDCl3, that is, the variation ratio (vr), is used for the first time as a measure of the hydrogen‐bonding strength of individual CO⋅⋅⋅HN bonds in ferrocenoyl peptides. In dipeptides with one intramolecular hydrogen bond between the pendant chains, for example, in dipeptide16, an equilibrium between hydrogen‐bonded and open forms is observed, as testified by a vr value of around 0.5. Higher peptides, such as tetrapeptide21, are able to form two intramolecular hydrogen bonds stabilizing one single conformation in CDCl3solution (vr≈0). Due to the low barrier of Cp‐ring rotation, new and unnatural hydrogen‐bonding patterns are emerging. The systematic work described herein lays a solid foundation for the rational design of metallocene peptides with unusual structures and properties.
Amide‐Based Molecular Knots as Platforms for Fluorescent Switches
Authors: Passaniti Paolo , Ceroni Paola , Balzani Vincenzo , Lukin Oleg , Yoneva Albena , Vögtle Fritz 
Published: May 2006

AbstractA series of amide‐based molecular knots equipped selectively with fluorescent dansyl and/or pyrenesulfonyl moieties were synthesized from the readily available tris(allyloxy)knotane. UV/Vis absorption spectra, emission spectra, and the emission lifetimes of the fluorescent knotanes were investigated in chloroform at 298 K. The absorption spectra of the knotanes correspond to those of mixtures of their UV‐active constituents. The fluorescence quantum yields and lifetimes of the dansyl and pyrenesulfonyl moieties are partly quenched by the knotane platform. In the KN(Da)2(Py) species, the fluorescent excited state of the dansyl units (λmax=510 nm) lies at lower energy than the fluorescent excited state of the pyrenesulfonyl unit (λmax=385 nm), the emission of which is accordingly quenched with sensitization of the dansyl fluorescence. In the KN(Ao)2(Da), KN(Ao)(Da)2, and KN(Da)3 species, the addition of acids causes the protonation of their dansyl units with a consequent decrease in the intensity of the dansyl band at 510 nm and appearance of the emission band of the protonated dansyl unit (λmax=340 nm). Each dansyl unit of KN(Ao)(Da)2 and KN(Da)3 undergoes the independent protonation. In these incompletely protonated knotanes the fluorescence of the protonated dansyl units is partly quenched by nonprotonated ones. These processes can be quantitatively reversed upon addition of a base. In KN(Da)2(Py), an increase of the fluorescence of its pyrenesulfonyl group is observed when the dansyl groups are protonated. The results obtained show that the readily available and easily functionalizable amide‐knotanes can be used as an interesting scaffold to obtain fluorescent switches.