Reversibility

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Reversibility

  • good reversibility
  • potential reversibility


  • Selected Abstracts


    Reversibility of estrogenic sex changes in zebrafish (Danio Rerio),

    ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2009
    Mia G. Larsen
    Abstract Development of male zebrafish (Danio rerio) courtship behavior was studied following estrogenic disruption of sexual differentiation. Sixty zebrafish were exposed at 28C to 5 ng/L (nominal concentration) of 17,-ethinylestradiol (EE2) from the egg stage until adulthood at four months of age, resulting in a female-biased sex ratio. Twenty-five EE2 -exposed phenotypic female zebrafish were subsequently held in clean water for eight months. During this period, eight phenotypic males developed. These phenotypic males demonstrated significant behavioral aberrations and a low fertilization rate compared to control males. [source]


    Improving the ON/OFF Ratio and Reversibility of Recording by Rational Structural Arrangement of Donor,Acceptor Molecules

    ADVANCED FUNCTIONAL MATERIALS, Issue 5 2010
    Ying Ma
    Abstract Organic molecules with donor,acceptor (D,A) structure are an important type of material for nanoelectronics and molecular electronics. The influence of the electron donor and acceptor units on the electrical function of materials is a worthy topic for the development of high-performance data storage. In this work, the effect of different D,A structures (namely D,,,A,,,D and A,,,D,,,A) on the electronic switching properties of triphenylamine-based molecules is investigated. Devices based on D,,,A,,,D molecules exhibit excellent write,read,erase characteristics with a high ON/OFF ratio of up to 106, while that based on A,,,D,,,A molecules exhibit irreversible switching behavior with an ON/OFF ratio of about (3.2,×,101),(1,×,103). Moreover, long retention time of the high conductance state and low threshold voltage are observed for the D,A switching materials. Accordingly, stable and reliable nanoscale data storage is achieved on the thin films of the D,A molecules by scanning tunneling microscopy. The influence of the arrangement of the D and A within the molecular backbone disclosed in this study will be of significance for improving the electronic switching properties (ON/OFF current ratio and reversibility) of new molecular systems, so as to achieve more efficient data storage through appropriate design strategies. [source]


    Role of Chronic Infection and Inflammation in the Gastrointestinal Tract in the Etiology and Pathogenesis of Idiopathic Parkinsonism

    HELICOBACTER, Issue 4 2005
    Part 1: Eradication of Helicobacter in the Cachexia of Idiopathic Parkinsonism
    ABSTRACT Background., Neuronal damage in idiopathic parkinsonism may be in response to ubiquitous occult infection. Since peptic ulceration is prodromal, Helicobacter is a prime candidate. Aim., To consider the candidature of Helicobacter in parkinsonism with cachexia. Methods., We explore the relationship between being underweight and inflammatory products in 124 subjects with idiopathic parkinsonism and 195 controls, and present the first case-series evidence of efficacy of Helicobacter eradication, in parkinsonism advanced to the stage of cachexia. Results., Association of a low body mass index with circulating interleukin-6 was specific to parkinsonism (p = .002), unlike that with antibodies against Helicobacter vacuolating-toxin and cytotoxicity-associated gene product (p < .04). Marked reversibility in both cachexia and disability of idiopathic parkinsonism followed Helicobacter heilmannii eradication in one case, Helicobacter pylori eradication in another, follow-up being , 3.5 years. The latter presented with postprandial bloating, and persistent nausea: following eradication, radioisotope gastric-emptying returned towards normal, and upper abdominal symptoms regressed. Reversibility of their cachexia/disability contrasts with the outcome of anti- Helicobacter therapy where eradication repeatedly failed (one case), and in non- Helicobacter gastritis (three cases). Anti-parkinsonian medication remained constant. Intestinal absorption and barrier function were normal in all. Conclusion., Categorization, according to presence or absence of Helicobacter infection, was a useful therapeutic tool in late idiopathic parkinsonism. [source]


    Reversibility of hepatic fibrosis in treated genetic hemochromatosis: A study of 36 cases,

    HEPATOLOGY, Issue 2 2006
    Ludivine Falize
    The current study was undertaken to assess whether fibrosis could regress under venesection therapy in patients with C282Y homozygous genetic hemochromatosis. The 36 patients studied were recruited from a subfile of our database consisting of 125 C282Y homozygotes with either severe fibrosis or cirrhosis (F3 or F4 fibrosis stage, respectively, according to the METAVIR grading system). The second liver biopsy was performed for management of liver cancer, extrahepatic surgery, or assessment of liver fibrosis. All paired biopsies were reviewed by two pathologists without knowledge of clinical data. Among the 13 patients who had F3 fibrosis on their initial liver biopsy, 3 had F0, 6 had F1, and 2 had F2 on their second liver biopsy. Among the 23 patients with cirrhosis on their initial liver biopsy, 1 had F0, 4 had F1, 3 had F2, and 2 had F3 on their second liver biopsy. When defining regression of fibrosis as a decrease of at least 2 METAVIR units, fibrosis regressed in 9 of 13 (69%) F3 and in 8 of 23 (35%) F4. When the ratio of gammaglobulins (g/L) to (platelets [n/mm3] × prothrombin activity [%]) was greater than 7.5, fibrosis never regressed. In conclusion, these data extend the concept of regression of fibrosis to patients with treated genetic hemochromatosis and suggest that some simple biochemical tests would be predictive of further regression of fibrosis as a result of venesection therapy. If confirmed on larger series, this could modify the ultrasound screening policy of hepatocellular carcinoma in genetic hemochromatosis. (HEPATOLOGY 2006;44:472,477.) [source]


    Reversibility of the Perovskite-to-Fluorite Phase Transformation in Lead-Based Thin and Ultrathin Films,

    ADVANCED MATERIALS, Issue 8 2008
    Geoff L. Brennecka
    As film thicknesses decrease below 50 nm, control of cation stoichiometry in Pb-based dielectrics becomes increasingly difficult, a problem that is exacerbated by interaction with technologically important Pt bottom electrodes. Post-crystallization annealing in a Pb-rich atmosphere is shown to be a general technique to reversibly convert low-permittivity Pb-deficient fluorite into ferroelectric high-permittivity stoichiometric perovskite with outstanding dielectric properties (see figure). [source]


    A Mutation in Mitochondrial Complex I Increases Ethanol Sensitivity in Caenorhabditis elegans

    ALCOHOLISM, Issue 4 2003
    Ernst-Bernhard Kayser
    Background: The gene gas-1 encodes the 49-kDa subunit of complex I of the mitochondrial electron transport chain in Caenorhabditis elegans. A mutation in gas-1 profoundly increases sensitivity to ethanol and decreases complex I-dependent metabolism in mitochondria. Methods: Mitochondria were isolated from wild-type and gas-1 strains of C. elegans. The effects of ethanol on complex I-, II-, and III-dependent oxidative phosphorylation were measured for mitochondria from each strain. Reversibility of the effects of ethanol was determined by measuring oxidative phosphorylation after removal of mitochondria from 1.5 M ethanol. The effects of ethanol on mitochondrial structure were visualized with electron microscopy. Results: We found that ethanol inhibited complex I,, II,, and III,dependent oxidative phosphorylation in isolated wild-type mitochondria at concentrations that immobilize intact worms. It is important to note that the inhibitory effects of ethanol on mitochondria from either C. elegans or rat skeletal muscle were reversible even at molar concentrations. Complex I activity was lower in mitochondria from gas-1 animals than in mitochondria from wild-type animals at equal ethanol concentrations. Complex II activity was higher in gas-1 than in wild-type mitochondria at all concentrations of ethanol. No difference was seen between the strains in the sensitivity of complex III to ethanol. Conclusions: The difference in ethanol sensitivities between gas-1 and wild-type nematodes results solely from altered complex I function. At the respective concentrations of ethanol that immobilize whole animals, mitochondria from each strain of worms displayed identical rates of complex I-dependent state 3 respiration. We conclude that a threshold value of complex I activity controls the transition from mobility to immobility of C. elegans. [source]


    Reversibility of ,Secondary Hypercalcitoninemia' After Kidney Transplantation

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2005
    Kyra A. Borchhardt
    Whether the increase of calcitonin (CT) concentration in patients with chronic kidney disease (CKD) is reversible or not after kidney transplantation is not known. We examined the effect of kidney transplantation on basal and pentagastrin-stimulated CT in CKD patients with elevated screening CT levels. Before transplantation, the median basal CT concentration of 17 patients was 31 pg/mL (13,76), and decreased to 8 pg/mL (4,28) at 23 months (2,34) after kidney transplantation (p < 0.00005). The maximum concentration of pentagastrin-stimulated CT was 63 pg/mL (25,110) before transplantation and decreased to 20 pg/mL (8,91) (p < 0.00005) thereafter. There was a linear association between CT and calcium as well as between phosphorus and parathyroid hormone at the time of screening. After transplantation, CT correlated with serum creatinine. Therefore, the increase of CT concentration in patients with impaired kidney function presumably reflects ,secondary hypercalcitoninemia' due to C-cell hyperactivity. [source]


    Crystal Symmetry and the Reversibility of Martensitic Transformations.

    CHEMINFORM, Issue 19 2004
    Kaushik Bhattacharya
    No abstract is available for this article. [source]


    Reversibility of acute intermediate phase bilirubin encephalopathy

    ACTA PAEDIATRICA, Issue 10 2009
    Thor Willy Ruud Hansen
    Abstract Aim:, To show the potential for reversing acute intermediate to advanced phase bilirubin encephalopathy. Methods:, Case studies. Results:, Six extremely jaundiced infants had symptoms of intermediate to advanced phase acute bilirubin encephalopathy. The infants were treated aggressively. Two patients had brain magnetic resonance imaging showing increased signals in the globus pallidus. On follow-up, all infants are neurologically normal. Conclusions:, Intermediate-to-advanced stage acute bilirubin encephalopathy may occasionally be reversible. These cases provide a strong argument in favour of rapid and aggressive intervention in infants presenting with extreme jaundice and neurological symptoms. [source]


    Rapid assessment and safe management of severe pulmonary hypertension with milrinone during orthotopic liver transplantation

    CLINICAL TRANSPLANTATION, Issue 4 2010
    Kyota Fukazawa
    Fukazawa K, Poliac LC, Pretto EA. Rapid assessment and safe management of severe pulmonary hypertension with milrinone during orthotopic liver transplantation. Clin Transplant 2010: 24: 515,519. © 2009 John Wiley & Sons A/S. Abstract:, The incidence of porto-pulmonary hypertension (PPHN) in patients with end stage liver disease is 8.5%. Evidence indicates that proceeding with orthotopic liver transplantation (OLT) in patients diagnosed with severe PPHN (mean pulmonary artery pressure [mPAP] > 45 mmHg) at the time of OLT surgery is associated with high perioperative mortality. We describe a case of severe PPHN that was diagnosed by right heart catheterization at the time of surgery. We quickly determined the reversibility of PPHN with a bolus of milrinone and proceeded with OLT. Further episodes of pulmonary hypertension were successfully managed with continuous milrinone infusion and transesophageal echocardiography monitoring. Reversibility via vasodilator trial after identification of high pulmonary artery pressures (PAP) may be an important indication of the feasibility of OLT. Milrinone may be useful for the rapid identification of the reversibility of high PAP and may be an effective agent to control abrupt increases in PAP during OLT. [source]


    Reducing threats to species: threat reversibility and links to industry

    CONSERVATION LETTERS, Issue 4 2010
    Laura R. Prugh
    Abstract Threats to species' persistence are typically mitigated via lengthy and costly recovery planning processes that are implemented only after species are at risk of extinction. To reduce overall threats and minimize risks to species not yet imperiled, a proactive and broad-scale framework is needed. Using data on threats to imperiled species in Canada to illustrate our approach, we link threats to industries causing the harm, thus providing regulators with quantitative data that can be used directly in cost-benefit and risk analyses to broadly reduce threat levels. We then show how ranking the ease of threat abatement and reversal assists prioritization by identifying threats that are easiest to mitigate as well as threats that are possible to abate but nearly impossible to reverse. This new framework increases the usefulness of widely available threat data for preventative conservation and species recovery. [source]


    The sources of skill in seriating cups in children, monkeys and apes

    DEVELOPMENTAL SCIENCE, Issue 1 2002
    Dorothy M. Fragaszy
    Is a concept of either reversibility or of hierarchical forms of combination necessary for skilled seriation? We examined this question by presenting seriating cups to adult capuchin monkeys and chimpanzees and to 11-, 16- and 21-month-old children. Capuchins and chimpanzees consistently created seriated sets with five cups, and placed a sixth cup into a previously seriated set. Children of all three ages created seriated five-cup sets less consistently than the capuchins and chimpanzees, and were rarely able to place a sixth cup into a seriated set. Twenty-one-month-olds produced more structures containing three or more cups than did the younger age groups, and these children also achieved seriated sets more frequently. Within all participant groups, success at seriating five cups was associated with the frequency of combining three or more cups, regardless of form. The ability to integrate multiple elements in persistent combinatorial activity is sufficient for the emergence of seriation in young children, monkeys and apes. Reliance on particular methods of combination and a concept of reversibility are later refinements that can enhance skilled seriation. [source]


    Recreational ecstasy use and the neurotoxic potential of MDMA: current status of the controversy and methodological issues

    DRUG AND ALCOHOL REVIEW, Issue 3 2006
    MICHAEL LYVERS
    Abstract The controversy over possible MDMA-induced serotonergic neurotoxicity in human recreational ecstasy users is examined critically in light of recent research findings. Although the designs of such studies have improved considerably since the 1990s, the evidence to date remains equivocal for a number of reasons, including (1) inconsistent findings on the existence and reversibility of persistent ecstasy-related serotonergic and cognitive deficits; (2) lack of clear association between changes in brain imaging measures and functional deficits attributed to MDMA-induced neurotoxicity; (3) the contribution of concomitant cannabis or other drug use to both brain imaging abnormalities and cognitive deficits; (4) methodological shortcomings such as failure to adequately match samples of ecstasy users and controls; (5) the questionable relevance of animal models of MDMA-induced neurotoxicity to typical human patterns of ecstasy use; and (6) the potential role of inherent pre-drug deficits in serotonergic systems, impulse control and executive cognitive function that may predispose to excessive use of drugs including ecstasy. Given the retrospective nature of nearly all studies of ecstasy users to date, the controversy over whether MDMA has ever caused neurotoxicity or cognitive deficit in human ecstasy users is likely to continue for some time without resolution. [source]


    Paste Electrode Based on Short Single-Walled Carbon Nanotubes and Room Temperature Ionic Liquid: Preparation, Characterization and Application in DNA Detection

    ELECTROANALYSIS, Issue 12 2008
    Xuzhi Zhang
    Abstract A paste electrode (SWNT&RTIL PE) has been prepared using carboxylic group-functionalized short single-walled carbon nanotubes (SWNTs) mixed with 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6, one kind of room temperature ionic liquid, RTIL). Its electrochemical behavior was investigated by cyclic voltammetry and electrochemical impedance spectroscopy in comparison with the paste electrode using mineral oil as a binder. Results highlighted the advantages of the paste electrode: not only higher conductivity, but also lower potential separation (,Ep), higher peak current (ip) and better reversibility towards dopamine (DA), methylene blue (MB) and K3[Fe(CN)6]. The SWNT&RTIL PE could be used to detect the number of guanine bases and adenine bases contents in per mol oligonucleotides according to the current response in the range of 0.05,2.0,nM. Based on the current response of guanine bases, oligonucleotides could be detected sensitively in the B,R buffer solution with a detection limit of 9.9,pM. The heterogeneous electron transfer rate constant (ks) of guanine bases contents in the oligonucleotides was investigated and its value was 0.90,s,1. In essence the SWNT&RTIL PE showed high sensitivity, reliability, stability and reproducibility for the detection of DNA. [source]


    Electrochemical Behavior of Catecholamines and Related Compounds at In Situ Surfactant Modified Carbon Paste Electrodes

    ELECTROANALYSIS, Issue 2-3 2007
    M.Carmen Blanco-López
    Abstract The voltammetric characteristics of catecholamines: epinephrine (E) and norepinephrine (NE) and related compounds: isoproterenol, metanephrine, L -dopa, methyldopa, vanillylmandelic acid (VMA), and homovanillic acid (HVA) at unmodified and in situ surfactant- modified carbon paste electrodes were comparatively evaluated. For the basic and amphoteric compounds the modification of the electrode surface with submicellar concentrations of anionic surfactants (sodium dodecylsulfate, sodium decylsulfate or sodium dodecylsulfonate) produce an important current enhancement in its oxidation and reduction peak current together with the improvement in the reversibility of the processes. These effects were explained in basis on electrostatic and hydrophobic interactions. On the other hand, the oxidation of acidic metabolites, HVA and VMA, was studied at electrodes modified in situ with cationic surfactants. Under certain conditions the surfactant could stabilise some of the electrochemical reaction intermediates, thus explaining the different voltammetric behaviour of HVA and VMA. [source]


    Glutathione Peroxidase-Based Amperometric Biosensor for the Detection of S -Nitrosothiols

    ELECTROANALYSIS, Issue 21 2006
    Mustafa Musameh
    Abstract A new biosensor is described for the detection of S -nitrosothiols (RSNOs) based on their decomposition by immobilized glutathione peroxidase (GPx), an enzyme containing selenocysteine residue that catalytically produces nitric oxide (NO) from RSNOs. The enzyme is entrapped at the distal tip of a planar amperometric NO sensor. The new biosensor shows good sensitivity, linearity, reversibility, and response times towards various RSNO species in PBS buffer, pH,7.4 . In most cases, the response time is less than 5,min, and the response is linear up to 6 ,M of the tested RSNO species. The lowest detection limit is obtained for S -nitrosocysteine (CysNO), at approx. 0.2,,M. The biosensor's sensitivity is not affected by the addition of EDTA as a chelating agent; an advantage over other potential catalytic enzymes that contain copper ion centers, such as CuZn-superoxide dismutase and xanthine oxidase. However, lifetime of the new sensor is limited, with sensitivity decrease of 50% after two days of use. Nonetheless, the new amperometric GPx based RSNO sensor could prove useful for detecting relative RSNO levels in biological samples, including whole blood. [source]


    Dramatic Effects of Ionic Liquid on Platinum Electrode Surface and Electron-Transfer Rates of meso -Tetraphenylporphyrins

    ELECTROANALYSIS, Issue 12 2006
    Afsaneh Safavi
    Abstract The effect of addition of a room temperature ionic liquid, 1-butyl-3-methyl imidazolium hexafluorophosphate [bmim][PF6], on the electrochemical behavior of different free-base para-substituted meso -tetraphenylporphyrins in dichloromethane solution has been studied using cyclic voltammetric technique. It has been found that the ionic liquid has the ability to regenerate platinum electrode surface and improves the reversibility of electrode processes. This has been true for the case of all the porphyrins studied. [source]


    Nanodiamond Thin Film Electrodes: Metal Electro-Deposition and Stripping Processes

    ELECTROANALYSIS, Issue 3 2003
    Hian, Lau Chi
    Abstract The properties of a nanodiamond thin film deposit formed on titanium substrates in a microwave-plasma enhanced CVD process, are investigated for applications in electroanalysis. The nanodiamond deposit consists of intergrown nano-sized platelets of diamond with a high sp2 carbon content giving it high electrical conductivity and electrochemical reactivity. Nanodiamond thin film electrodes (of approximately 2,,m thickness) are characterized by electron microscopy and electrochemical methods. First, for a reversible one electron redox system, Ru(NH3)63+/2+, nanodiamond is shown to give well-defined diffusion controlled voltammetric responses. Next, metal deposition processes are shown to proceed on nanodiamond with high reversibility and high efficiency compared to processes reported on boron-doped diamond. The nucleation of gold is shown to be facile at edge sites, which are abundant on the nanodiamond surface. For the deposition and stripping of both gold and copper, a stripping efficiency (the ratio of electro-dissolution charge to electro-deposition charge) of close to unity is detected even at low concentrations of analyte. The effect of thermal annealing in air is shown to drastically modify the electrode characteristics probably due to interfacial oxidation, loss of active sp2 sites, and loss of conductivity. [source]


    Sorption irreversibility of 1,4-dichlorobenzene in two natural organic matter,rich geosorbents

    ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2009
    Michael Sander
    Abstract Hysteresis, a frequently observed phenomenon in sorption studies, is inconsistent with the key assumption of sorption reversibility in most fate and bioavailability models. Therefore, a study of the underlying causes of hysteresis is essential. Carbon-radiolabeled 1,4-dichlorobenzene (DCB) isotope tracer exchange was carried out at select points along the isotherms of DCB in a brown coal and a peat soil, holding total DCB concentration constant. Tracer exchange was performed both in the forward (sorption) and reverse (desorption) directions at the bulk sorption points and in the desorption direction at the corresponding bulk desorption points. Bulk DCB isotherms showed concentration-dependent hysteresis. However, tracer reequilibration in all cases was consistent with free exchange between sorbed and aqueous-phase molecules. These results rule out common experimental artifacts and demonstrate that sorption of bulk DCB is truly hysteretic (i.e., irreversible). The differences in rates between bulk and tracer sorption and desorption are consistent with the coupling of bulk DCB diffusion to other processes that retard equilibration, which we assign to matrix swelling or shrinking. Hysteresis is attributed to matrix deformation,specifically, to inelastic expansion and creation of voids accommodating sorbate molecules in the matrix, which leads to enhanced affinity in the desorption step. Comparing the results to previous results for naphthalene in the coal, we find that irreversible effects are similar for DCB and naphthalene in the coal but differ for DCB between the two sorbents. An explanation based on the different physical properties of these sorbents is provided. Solid-phase extraction of equilibrated DCB with Tenax® revealed a highly desorption-resistant fraction. While too small to account for the observed hysteresis, this fraction may represent molecules that become trapped as the matrix collapses and simultaneously stiffens during abrupt desorption. [source]


    Effects of ethynylestradiol on the reproductive physiology in zebrafish (Danio rerio): Time dependency and reversibility

    ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2002
    Kris Van den Belt
    Abstract Environmental pollution with natural or synthetic estrogens may pose a serious threat to reproduction of wildlife species. This study describes the effects of 17-,-ethynylestradiol (EE2) on fish reproductive organs in a laboratory model. Adult zebrafish were semistatically exposed to nominal concentrations of 0, 10, and 25 ng/L EE2 for 24 d and then transferred to EE2-free medium. Gonadosomatic index (GSI), plasma vitellogenin concentration (VTG), and histology of the gonads (control and 10 ng/L only) were examined as a function of time. It was found that EE2 has an adverse impact on both male and female reproductive organs. Notably in females, gonadal changes were observed through histological evaluation after 3 d of exposure to 10 ng/L EE2, and this was followed by a reduction of GSI at day 6 of exposure. In males, a reduction of GSI and altered testis histology was found after 24 d of exposure to 10 ng/L. The observed effects on the ovary after EE2 exposure, combined with complete recovery after 24 d, is considered to be triggered by feedback at the level of the pituitary. In both males and females, VTG was induced in response to EE2 and normalized during the recovery period. The observed correlation between VTG and ovarian somatic index (OSI) demonstrates that excessive VTG induction may be predictive for adverse effects of EE2 on ovarian function in female zebrafish. These results indicate that long-term stimulation by synthetic estrogens such as EE2 might impair reproductive function in zebrafish in a reversible manner. [source]


    Early detection and prevention of delirium in older patients with cancer

    EUROPEAN JOURNAL OF CANCER CARE, Issue 5 2004
    K. MILISEN phd, rn 1
    Delirium poses a common and multifactorial complication in older patients with cancer. Delirium independently contributes to poorer clinical outcomes and impedes communication between patients with cancer, their family and health care providers. Because of its clinical impact and potential reversibility, efforts for prevention, early recognition or prompt treatment are critical. However, nurses and other health care providers often fail to recognize delirium or misattribute its symptoms to dementia, depression or old age. Yet, failure to determine an individual's risk for delirium can initiate the cascade of negative events causing additional distress for patients, family and health care providers alike. Therefore, parameters for determining an individual's risk for delirium and guidelines for the routine and systematic assessment of cognitive functioning are provided to form a basis for the prompt and accurate diagnosis of delirium. Guidelines for the prevention and treatment of delirium are also discussed. [source]


    Lenalidomide and dexamethasone for the treatment of refractory/relapsed multiple myeloma: dosing of lenalidomide according to renal function and effect on renal impairment

    EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2010
    Meletios A. Dimopoulos
    Abstract Objectives:, Lenalidomide and dexamethasone (LenDex) is an active regimen for relapsed/refractory multiple myeloma (MM). However, there is limited data for the effect of LenDex on renal impairment (RI) and on renal reversibility. Patients & Methods:, Fifty consecutive patients with relapsed/refractory MM received LenDex in 28-d cycles. Median lines of previous therapies were 2 (range: 1,6). Lenalidomide was administered on days 1,21 according to creatinine clearance (CrCl), while dexamethasone was given at a dose of 40 mg on days 1,4 and 15,18 for the first four cycles and only on days 1,4 thereafter. Results:, Twelve patients (24%) had RI at baseline, defined as CrCl < 50 mL/min. Most patients were pretreated with either thalidomide or bortezomib and > 50% of them were refractory to both drugs. At least partial response was documented in 60.5% and 58% of patients with and without RI. Median progression-free survival (PFS) and overall survival (OS) for all patients was 9 and 16 months, respectively. RI was not associated with an inferior PFS or OS. There were no differences in the incidence of adverse events among patients with and without RI. Three of 12 patients with RI (25%) achieved complete renal response and two (16%) achieved minor renal response with LenDex. Conclusions:, We conclude that LenDex is an active treatment even in heavily pretreated MM. With dosing of lenalidomide according to renal function, LenDex can be administered to patients with RI (who may not have other treatment options) without excessive toxicity. Furthermore, LenDex may improve the renal function in approximately 40% of patients with RI. [source]


    Synthesis, X-ray Crystal Structures and Electrochemistry of (Indenyl)ruthenium Complexes Containing dppf and Heterocyclic Thiolato/Thione Ligands

    EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 1 2008
    Sin Yee Ng
    Abstract A number of (indenyl)ruthenium complexes containing dppf [1,1,-bis(diphenylphosphanyl)ferrocene] and heterocyclic thiolato/thione ligands have been synthesized. All the complexes were fully characterized by microanalytical and spectroscopic techniques, together with X-ray diffraction analyses for those containing the benzothiazolato (thiolato) and the thiadiazole (thione) ligands. Cyclic voltammetry (CV) experiments indicated that these complexes can be oxidized in three one-electron processes at positive potentials. Differences in chemical reversibility observed during variable-temperature CV experiments indicated that it was likely that the oxidation processes occurred at two electronically noncommunicating sites within the molecules. One site could be assigned as the oxidation of the Ru ion (two one-electron processes), whilst the second site was assigned as the oxidation of the dppf (one one-electron process). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source]


    Amino-phosphanes in RhI -Catalyzed Hydroformylation: New Mechanistic Insights Using D2O as Deuterium-Labeling Agent

    EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 1 2006
    Jacques Andrieu
    Abstract In previous work, we have demonstrated that the dangling amino group in amino-phosphane ligands increases the rate of Rh-catalyzed styrene hydroformylation as a function of the amino group basicity and of the distance between the P and N functions. We now report additional stereochemical and mechanistic insights resulting from new catalytic experiments performed with Rh-,-P,N catalytic systems in the presence of D2O. In addition to the expected D0 product, the formation of the ,-D1 aldehyde, PhCH(CH2D)CHO was observed in all cases by 1H and 13C NMR spectroscopy, indicating that H/D exchange occurs for the rhodium-hydride complex. Minor amounts of a ,-D2 product, PhCH(CHD2)CHO, were also formed under certain conditions, demonstrating the reversibility of the olefin coordination step. The composition of the aldehyde mixture is slightly affected by the nature of the catalytic precursor or the P,N ligand used. In the specific case of the ,-P,N ligand [,-P,N = (SAr,SC)-Ph2PCH{o -C6H4Cl(Cr(CO)3)}NHPh], in combination with the [RhCl(COD)]2 precatalyst, products PhCD(CH3)CHO (,-D1) and PhCD(CH2D)CHO (,,,-D2) were also produced. This result suggests a reversible deprotonation assisted by an intramolecular H-bonding interaction between the dangling ammonium function and the carbonyl moiety. This isotopic exchange process decreases the asymmetric induction from 14 to 7,% ee when using the enantiopure version of this ligand. Aldehydes bearing a D atom on the formyl group, e.g. PhCH(CH3)CDO, were never observed. The latter observation excludes protonolysis of the rhodium-acyl intermediate as the aldehyde forming step. In addition, it also excludes a bimolecular reaction involving the rhodium-acyl and rhodium-hydride intermediates.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source]


    Chronic cocaine sensitizes striatal GABAergic synapses to the stimulation of cannabinoid CB1 receptors

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2007
    Diego Centonze
    Abstract Behavioural studies indicate that cannabinoid receptors are implicated in cocaine addiction. The synaptic underpinning of cocaine,cannabinoid receptor interaction is however, obscure. We have studied electrophysiologically the sensitivity of cannabinoid receptors modulating synaptic transmission in the striatum of rats exposed to cocaine. One-day treatment with cocaine did not modify the synaptic response to HU210, a cannabinoid CB1 receptor agonist. Seven days cocaine-treatment, conversely, caused conditioned place preference, and sensitized striatal GABAergic synapses to the presynaptic effect of cannabinoid CB1 receptor stimulation. The cannabinoid receptor-induced modulation of glutamate transmission was unaltered by cocaine. Furthermore, the effects of chronic cocaine on cannabinoid-mediated regulation of striatal GABA synapses were attenuated one week after the discontinuation of cocaine, and absent two weeks later, indicating the progressive reversibility of the adaptations of cannabinoid system during abstinence of drug consumption. Our data support the concept that modulation of cannabinoid receptors might be useful against drug abuse. [source]


    ,-Conotoxin CVIB differentially inhibits native and recombinant N- and P/Q-type calcium channels

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2007
    Leonid Motin
    Abstract ,-Conotoxins are routinely used as selective inhibitors of different classes of voltage-gated calcium channels (VGCCs) in excitable cells. In the present study, we examined the potent N-type VGCC antagonist ,-conotoxin CVID and non-selective N- and P/Q-type antagonist CVIB for their ability to block native VGCCs in rat dorsal root ganglion (DRG) neurons and recombinant VGCCs expressed in Xenopus oocytes. ,-Conotoxins CVID and CVIB inhibited depolarization-activated whole-cell VGCC currents in DRG neurons with pIC50 values of 8.12 ± 0.05 and 7.64 ± 0.08, respectively. Inhibition of Ba2+ currents in DRG neurons by CVID (, 66% of total) appeared to be irreversible for >,30 min washout, whereas Ba2+ currents exhibited rapid recovery from block by CVIB (, 80% within 3 min). The recoverable component of the Ba2+ current inhibited by CVIB was mediated by the N-type VGCC, whereas the irreversibly blocked current (, 22% of total) was attributable to P/Q-type VGCCs. ,-Conotoxin CVIB reversibly inhibited Ba2+ currents mediated by N- (CaV2.2) and P/Q- (CaV2.1), but not R- (CaV2.3) type VGCCs expressed in Xenopus oocytes. The ,2,1 auxiliary subunit co-expressed with CaV2.2 and CaV2.1 reduced the sensitivity of VGCCs to CVIB but had no effect on reversibility of block. Determination of the NMR structure of CVIB identified structural differences to CVID that may underlie differences in selectivity of these closely related conotoxins. ,-Conotoxins CVIB and CVID may be useful as antagonists of N- and P/Q-type VGCCs, particularly in sensory neurons involved in processing primary nociceptive information. [source]


    Repeated restraint stress suppresses neurogenesis and induces biphasic PSA-NCAM expression in the adult rat dentate gyrus

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2003
    Kara Pham
    Abstract Chronic restraint stress has been shown to induce structural remodelling throughout the interconnected dentate gyrus-CA3 fields. To find out how this stressor affects the rate of adult hippocampal neurogenesis, we subjected rats to acute or chronic restraint stress and assessed the proliferation, survival and differentiation of newly born cells in the dentate gyrus. We also examined polysialylated neural cell adhesion molecule expression, a molecule normally expressed in immature neurons and important for morphological plasticity. The results show that acute restraint stress did not change either the proliferation of dentate gyrus precursor cells or the expression of polysialylated neural cell adhesion molecule, whereas 3 weeks of chronic restraint stress suppressed proliferation by 24% and increased polysialylated neural cell adhesion molecule expression by 40%. The study was extended for an additional 3 weeks to trace the survival and development of the cells born after the initial 3 weeks of restraint. Rats subjected to 6 weeks of daily restraint stress exhibited suppressed cell proliferation and attenuated survival of the recently born cells after the extended time course, resulting in a 47% reduction of granule cell neurogenesis. Furthermore, 6 weeks of chronic stress significantly reduced the total number of granule cells by 13% and the granule cell layer volume by 5%. Expression of polysialylated neural cell adhesion molecule followed a biphasic time course, displaying a significant up-regulation after 3 weeks of daily restraint stress that was lost after 6 weeks of stress. These studies may help us understand the basis for hippocampal shrinkage and raise questions about the ultimate reversibility of the effects of chronic stress. [source]


    Effective inhibition of melanosome transfer to keratinocytes by lectins and niacinamide is reversible

    EXPERIMENTAL DERMATOLOGY, Issue 7 2005
    Amanda Greatens
    Abstract:, Skin pigmentation results in part from the transfer of melanized melanosomes synthesized by melanocytes to neighboring keratinocytes. Plasma membrane lectins and their glycoconjugates expressed by these epidermal cells are critical molecules involved in this transfer process. In addition, the derivative of vitamin B3, niacinamide, can inhibit melanosome transfer and induce skin lightening. We investigated the effects of these molecules on the viability of melanocytes and keratinocytes and on the reversibility of melanosome-transfer inhibition induced by these agents using an in vitro melanocyte,keratinocyte coculture model system. While lectins and neoglycoproteins could induce apoptosis in a dose-dependent manner to melanocytes or keratinocytes in monoculture, similar dosages of the lectins, as opposed to neoglycoproteins, did not induce apoptosis to either cell type when treated in coculture. The dosages of lectins and niacinamide not affecting cell viability produced an inhibitory effect on melanosome transfer, when used either alone or together in cocultures of melanocytes,keratinocytes. Cocultures treated with lectins or niacinamide resumed normal melanosome transfer in 3 days after removal of the inhibitor, while cocultures treated with a combination of lectins and niacinamide demonstrated a lag in this recovery. Subsequently, we assessed the effect of niacinamide on facial hyperpigmented spots using a vehicle-controlled, split-faced design human clinical trial. Topical application of niacinamide resulted in a dose-dependent and reversible reduction in hyperpigmented lesions. These results suggest that lectins and niacinamide at concentrations that do not affect cell viability are reversible inhibitors of melanosome transfer. [source]


    Bacterial IscU is a well folded and functional single domain protein

    FEBS JOURNAL, Issue 11 2004
    Salvatore Adinolfi
    Iron,sulfur clusters are widely represented in most organisms, but the mechanism of their formation is not fully understood. Of the two main proteins involved in cluster formation, NifS/IscS and NifU/IscU, only the former has been well studied from a structural point of view. Here we report an extensive structural characterization of Escherichia coli IscU. We show by a variety of physico-chemical techniques that E. coli IscU construct can be expressed to high purity as a monomeric protein, characterized by an ,, fold with high ,-helix content. The high melting temperature and the reversibility of the thermal unfolding curve (as measured by CD spectroscopy) hint at a well ordered stable fold. The excellent dispersion of cross peaks in the 1H- 15N correlation spectrum is consistent with these observations. Monomeric E. coli IscU is able to provide a scaffold for Iron,sulfur cluster assembly, but has no direct interaction with either Fe(II) or Fe(III) ions, suggesting the need of further partners to achieve a stable interaction. [source]


    Intracellular trafficking and release of intact edible mushroom lectin from HT29 human colon cancer cells

    FEBS JOURNAL, Issue 7 2000
    Lu-Gang Yu
    Our previous studies have shown that the Gal,1,3GalNAc,- (Thomsen,Friedenreich antigen)-binding lectin from the common edible mushroom Agaricus bisporus (ABL) reversibly inhibits cell proliferation, and this effect is a consequence of inhibition of nuclear localization sequence-dependent nuclear protein import after ABL internalization [Yu, L.G., Fernig, D.G., White, M.R.H., Spiller, D.G., Appleton, P., Evans, R.C., Grierson, I., Smith, J.A., Davies, H., Gerasimenko, O.V., Petersen, O.H., Milton, J.D. & Rhodes, J.M. (1999) J. Biol. Chem.274, 4890,4899]. Here, we have investigated further the intracellular trafficking and fate of ABL after internalization in HT29 human colon cancer cells. Internalization of 125I-ABL occurred within 30 min of the lectin being bound to the cell surface. Subcellular fractionation after pulse labelling of the cells with 125I-ABL for 2 h at 4 °C followed by culture of the cells at 37 °C demonstrated a steady increase in radioactivity in a crude nuclear extract. The radioactivity in this extract reached a maximum after 10 h and declined after 20 h. Release of ABL from the cell, after pulse labelling, was assessed using both fluorescein isothiocyanate-labelled ABL and 125I-ABL and was slow, with a t1/2 of 48 h. Most of the 125I-ABL both inside cells and in the medium remained intact, as determined by trichloroacetic acid precipitation and SDS/PAGE, and after 48 h only 22 ± 2% of ABL in the medium and 14 ± 2% inside the cells was degraded. This study suggests that the reversibility of the antiproliferative effect of ABL is associated with its release from cells after internalization. The internalization and subsequent slow release, with little degradation of ABL, reflects the tendency of lectins to resist biodegradation and implies that other endogenous or exogenous lectins may be processed in this way by intestinal epithelial cells. [source]