bluuebunny/crossref_metadata_2025_split huggingface dataset:
Motivation for lifestyle changes to improve health in people with impaired glucose tolerance
Authors: Hansen Elisabeth , Landstad Bodil J. , Hellzén Ove , Svebak Sven 
Published: December 2010

Scand J Caring Sci; 2011; 25; 484–490

Motivation for lifestyle changes to improve health in people with impaired glucose tolerance Aim:  To identify factors that could have motivational significance for lifestyle change to facilitate the reduction of Impaired Glucose Tolerance (IGT) and, consequently, the risk of having type 2 diabetes.Methods:  Eighteen people living in a municipality in central Norway participated in the study. A large‐scale public health screening study had defined them as people with IGT. The participants took part in a semi‐structured interview that focused on four aspects of everyday lifestyle: (1) structure and rhythm, (2) physical health, (3) physical activity and (4) social relations.Results:  The interviews showed that the participants in the study changed their priorities regarding daily living. Results indicated four domains of motivational factors that appeared as significant for lifestyle changes. The participants attributed great significance to their physical health and were strongly motivated to prevent disease development by improvement of everyday structure and rhythm, reduction of sickness risk, activity level and social relation. Research indicates, however, that lasting lifestyle changes take time and that health care support must be adapted to the individual in light of their social setting.Conclusion:  Persons with IGT appear to benefit from lifestyle changes along four dimensions of motivational significance: Structure and rhythm, Sickness concerns, Activity levels, Social relations. This means that attention needs to be more carefully tailored the individual along these four dimensions than has been the case in traditional health care.
Resistance of skin fibroblasts to peroxide and UV damage predicts hearing loss in aging mice
Authors: Miller Richard A. , Dolan David , Han Melissa , Kohler William , Schacht Jochen 
Published: December 2010

SummaryThose mice whose skin‐derived primary fibroblast cell lines resist lethal injury induced by hydrogen peroxide or UV light show lower age‐related decline in hearing. Skin cell lines may provide an easily accessible surrogate index of intrinsic stress resistance that varies among individuals and influences the pace of neurosensory decline in aging mice.
Trapping and dissociation of propafenone derivatives in HERG channels
Authors: Windisch A , Timin EN , Schwarz T , Stork‐Riedler D , Erker T , Ecker GF , Hering S 
Published: December 2010

BACKGROUND AND PURPOSEHumanether‐a‐go‐gorelated gene (HERG) channel inhibitors may be subdivided into compounds that are trapped in the closed channel conformation and others that dissociate at rest. The structural peculiarities promoting resting state dissociation from HERG channels are currently unknown. A small molecule‐like propafenone is efficiently trapped in the closed HERG channel conformation. The aim of this study was to identify structural moieties that would promote dissociation of propafenone derivatives.EXPERIMENTAL APPROACHHumanether‐a‐go‐gorelated gene channels were heterologously expressed in Xenopus oocytes and potassium currents were recorded using the two‐microelectrode voltage clamp technique. Recovery from block by 10 propafenone derivatives with variable side chains, but a conserved putative pharmacophore, was analysed.KEY RESULTSWe have identified structural determinants of propafenone derivatives that enable drug dissociation from the closed channel state. Propafenone and four derivatives with ‘short’ side chains were trapped in the closed channel. Five out of six bulky derivatives efficiently dissociated from the channel at rest. One propafenone derivative with a similar bulk but lacking an H‐bond acceptor in this region was trapped. Correlations were observed between molecular weight and onset of channel block as well as between pKaand recovery at rest.CONCLUSION AND IMPLICATIONSThe data show that extending the size of a trapped HERG blocker‐like propafenone by adding a bulky side chain may impede channel closure and thereby facilitate drug dissociation at rest. The presence of an H‐bond acceptor in the bulky side chain is, however, essential.
Animal modelling of traumatic brain injury in preclinical drug development: where do we go from here?
Authors: Marklund Niklas , Hillered Lars 
Published: December 2010

Traumatic brain injury (TBI) is the leading cause of death and disability in young adults. Survivors of TBI frequently suffer from long‐term personality changes and deficits in cognitive and motor performance, urgently calling for novel pharmacological treatment options. To date, all clinical trials evaluating neuroprotective compounds have failed in demonstrating clinical efficacy in cohorts of severely injured TBI patients. The purpose of the present review is to describe the utility of animal models of TBI for preclinical evaluation of pharmacological compounds. No single animal model can adequately mimic all aspects of human TBI owing to the heterogeneity of clinical TBI. To successfully develop compounds for clinical TBI, a thorough evaluation in several TBI models and injury severities is crucial. Additionally, brain pharmacokinetics and the time window must be carefully evaluated. Although the search for a single‐compound, ‘silver bullet’ therapy is ongoing, a combination of drugs targeting various aspects of neuroprotection, neuroinflammation and regeneration may be needed. In summary, finding drugs and prove clinical efficacy in TBI is a major challenge ahead for the research community and the drug industry. For a successful translation of basic science knowledge to the clinic to occur we believe that a further refinement of animal models and functional outcome methods is important. In the clinical setting, improved patient classification, more homogenous patient cohorts in clinical trials, standardized treatment strategies, improved central nervous system drug delivery systems and monitoring of target drug levels and drug effects is warranted.LINKED ARTICLESThis article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visithttp://dx.doi.org/10.1111/bph.2011.164.issue‐4
Role of angiotensin II receptor subtype activation in cognitive function and ischaemic brain damage
Authors: Horiuchi Masatsugu , Mogi Masaki 
Published: December 2010

Recent clinical studies have demonstrated that angiotensin II type 1 (AT1) receptor blockers (ARBs) reduce the onset of stroke, stroke severity and the incidence and progression of Alzheimer's disease and dementia. We can expect that ARBs exert these effects by both AT1receptor blockade and angiotensin II type 2 (AT2) receptor stimulation. Moreover, recent experimental results support the notion that AT2receptor stimulation with AT1receptor blockade could contribute to protection against ischaemic brain damage at least partly due to an increase in cerebral blood flow and decrease in oxidative stress, and prevent cognitive decline. Cellular therapy has been focused on as a new therapeutic approach to restore injured neurons. In this context, it has been reported that AT2receptor stimulation enhances neurite outgrowth and decreases neural damage, thereby enhancing neurogenesis. Moreover, additional beneficial effects of ARBs with an AT1receptor blocking action with a partial peroxisome proliferator‐activated receptor (PPAR)‐γ agonistic effect have been reported, and interaction of AT2receptor activation and PPAR‐γ might be involved in these ARBs' effects. This article reviews the effects of regulation of activation of angiotensin II receptor subtypes on ischaemic brain damage and cognitive function, focusing on the effects of AT2receptor stimulation.LINKED ARTICLESThis article is one of a set of reviews submitted toBJPin connection with talks given at the September 2010 meeting of the International Society of Hypertension in Vancouver, Canada. To view the other articles in this collection visithttp://dx.doi.org/10.1111/j.1476‐5381.2011.01235.x,http://dx.doi.org/10.1111/j.1476‐5381.2011.01260.xandhttp://dx.doi.org/10.1111/j.1476‐5381.2011.01366.x
Ca2+entry following P2X receptor activation induces IP3receptor‐mediated Ca2+release in myocytes from small renal arteries
Authors: Povstyan Oleksandr V , Harhun Maksym I , Gordienko Dmitri V 
Published: December 2010

BACKGROUND AND PURPOSEP2X receptors mediate sympathetic control and autoregulation of the renal circulation triggering contraction of renal vascular smooth muscle cells (RVSMCs) via an elevation of intracellular Ca2+concentration ([Ca2+]i). Although it is well‐appreciated that the myocyte Ca2+signalling system is composed of microdomains, little is known about the structure of the [Ca2+]iresponses induced by P2X receptor stimulation in vascular myocytes.EXPERIMENTAL APPROACHESUsing confocal microscopy, perforated‐patch electrical recordings, immuno‐/organelle‐specific staining, flash photolysis and RT‐PCR analysis we explored, at the subcellular level, the Ca2+signalling system engaged in RVSMCs on stimulation of P2X receptors with the selective agonistαβ‐methylene ATP (αβ‐meATP).KEY RESULTSRT‐PCR analysis of single RVSMCs showed the presence of genes encoding inositol 1,4,5‐trisphosphate receptor type 1(IP3R1) and ryanodine receptor type 2 (RyR2). The amplitude of the [Ca2+]itransients depended onαβ‐meATP concentration. Depolarization induced by 10 µmol·L−1αβ‐meATP triggered an abrupt Ca2+release from sub‐plasmalemmal (‘junctional’) sarcoplasmic reticulum enriched with IP3Rs but poor in RyRs. Depletion of calcium stores, block of voltage‐gated Ca2+channels (VGCCs) or IP3Rs suppressed the sub‐plasmalemmal [Ca2+]iupstroke significantly more than block of RyRs. The effect of calcium store depletion or IP3R inhibition on the sub‐plasmalemmal [Ca2+]iupstroke was attenuated following block of VGCCs.CONCLUSIONS AND IMPLICATIONSDepolarization of RVSMCs following P2X receptor activation induces IP3R‐mediated Ca2+release from sub‐plasmalemmal (‘junctional’) sarcoplasmic reticulum, which is activated mainly by Ca2+influx through VGCCs. This mechanism provides convergence of signalling pathways engaged in electromechanical and pharmacomechanical coupling in renal vascular myocytes.
Geranylated flavanone tomentodiplacone B inhibits proliferation of human monocytic leukaemia (THP‐1) cells
Authors: Kollár Peter , Bárta Tomáš , Závalová Veronika , Šmejkal Karel , Hampl Aleš 
Published: December 2010

BACKGROUND AND PURPOSEPaulownia tomentosa is a rich source of geranylated flavanones, some of which we have previously shown to have cytotoxic activity. To identify members of this class of compounds with cytostatic effects, we assessed the effects of the geranylated flavanone tomentodiplacone B (TOM B) on cell cycle progression and cell cycle regulatory pathways of THP‐1 human monocytic leukaemia cells.EXPERIMENTAL APPROACHCell viability was measured by dye exclusion and proliferation by WST‐1 assays; cell cycle was monitored by flow cytometry. Regulatory proteins were assessed by immunoprecipitation and kinase assays, and Western blotting.KEY RESULTSTomentodiplacone B had no effect during the first 24 h of cell growth at concentrations between 1 and 2.5 µM, but inhibited cell growth in a dose‐dependent manner at concentrations of 5 µM or higher. Growth inhibition during the first 24 h of exposure to TOM B was not accompanied by cytotoxicity as cells were accumulated in G1 phase dose‐dependently. This G1 phase accumulation was associated with down‐regulation of cyclin‐dependent kinase 2 activity and also protein levels of cyclins E1 and A2. However, key stress‐related molecules (γ‐H2AX, p53 and p21) were not induced, suggesting that TOM B acts by directly inhibiting the cyclin‐dependent kinase 2 signalling pathway rather than initiating DNA damage or cellular stress.CONCLUSIONS AND IMPLICATIONSOur study provides the first evidence that TOM B directly inhibits proliferation of human monocytic leukaemia cells, and thus is a potential anticancer agent, preventing leukaemia cells from progressing from G1 phase into DNA synthesis.
New perspectives regarding β2‐adrenoceptor ligands in the treatment of asthma
Authors: Walker JKL , Penn RB , Hanania NA , Dickey BF , Bond RA 
Published: December 2010

In the last two decades several significant changes have been proposed in the receptor theory that describes how ligands can interact with G protein‐coupled receptors (GPCRs). Here we briefly summarize the evolution of receptor theory and detail recent prominent advances. These include: (i) the existence of spontaneously active GPCRs that are capable of signalling even though they are unoccupied by any ligand; (ii) the discovery of ligands that can inactivate these spontaneously active receptors; (iii) the notion that a ligand may simultaneously activate more than one GPCR signalling pathway; and (iv) the notion that certain ligands may be able to preferentially direct receptor signalling to a specific pathway. Because the data supporting these receptor theory ideas are derived primarily from studies using artificial expression systems, the physiological relevance of these new paradigms remains in question. As a potential example of how these new perspectives in receptor theory relate to drug actions and clinical outcomes, we discuss their relevance to the recent controversy regarding the chronic use of β2‐adrenoceptor agonists in the treatment of asthma.LINKED ARTICLESThis article is part of a themed issue on Respiratory Pharmacology. To view the other articles in this issue visithttp://dx.doi.org/10.1111/bph.2011.163.issue‐1
Minerals in Dialysis Therapy: An Introduction
Authors: Weisberg Lawrence S. , Zanger Ron 
Published: December 2010

The 180 l of glomerular filtrate formed each day contain some 1100 g (2.5 pounds) of sodium chloride, of which only 5–10 g are excreted in the urine – 95% is reabsorbed by the tubules. Some 425 g (nearly a pound) of sodium bicarbonate and 145 g of glucose are filtered, and more than 99% of both are reabsorbed. Also filtered, only to be reabsorbed, are substantial quantities of potassium, calcium, magnesium, phosphate, sulfate, amino acids, vitamins, and many other substances valuable to the body.It is no exaggeration to say that the composition of the blood is determined not by what the mouth takes in but by what the kidneys keep: they are the master chemists of our internal environment, which, so to speak, they manufacture in reverse by working it over completely some fifteen times a day…Our bones, muscles, glands, even our brains are called upon to do only one kind of physiological work, but our kidneys are called upon to perform an innumerable variety of operations. Bones can break, muscles can atrophy, glands can loaf, even the brain can go to sleep, without immediately endangering our survival; but should the kidneys fail to manufacture the proper kind of blood neither bone, muscle, gland nor brain could carry on (1).
Thrombectomy of Arteriovenous Dialysis Grafts with Early Failure: Is it Worthwhile?
Authors: Mudunuri Vijay , O’Neal Jeremy C. , Allon Michael 
Published: December 2010

AbstractArteriovenous dialysis grafts are prone to frequent thrombosis, which can be treated either percutaneously or surgically. To assess the outcomes of grafts treated for early thrombosis, we retrospectively queried a prospective, computerized database, and identified all grafts placed over a 5‐year period that required thrombectomy within 60 days of creation. Technical success was defined as the immediate restoration of graft patency. Primary patency was calculated from thrombectomy to the next intervention, and cumulative graft survival from thrombectomy to permanent graft failure. Of 709 grafts placed, 98 grafts (14%) clotted within 60 days of creation, including 63 (9%) within 30 days of graft creation, and 35 (5%) at 31–60 days after creation. Most (95%) of grafts clotting within 30 days of creation underwent surgical thrombectomy, whereas 71% of those clotting at 31–60 days underwent percutaneous thrombectomy. The immediate technical success was 82% and 80% in grafts undergoing thrombectomy at <30 vs. 31–60 days (p = 0.76). The median primary patency was 11 and 23 days (p = 0.46), and the median cumulative graft survival was 27 and 163 days, respectively (p = 0.29). In conclusion, thrombectomy within 60 days of graft creation is associated with poor primary and cumulative graft patency, and may not be worthwhile.
Safety of Low Volume Iodinated Contrast Administration for Arteriovenous Fistula Intervention in Chronic Kidney Disease Stage 4 or 5 Utilizing a Bicarbonate Prophylaxis Strategy
Authors: Eisenhart Elizabeth , Benson Scott , Lacombe Patricia , Himmelfarb Jonathan , Zimmerman Robert , Schimelman Brad , Parker Mark G. 
Published: December 2010

AbstractEfforts to increase the number of functioning arteriovenous fistulas in chronic kidney disease (CKD) stages 4 and 5 have been impacted by concerns about the risk for contrast‐induced nephropathy during diagnostic and interventional procedures for poorly developed fistulas. We conducted a prospective observational study of low volume iodinated contrast administration for fistulography and angioplasty in a CKD stage 4 and stage 5 population pretreated with a sodium bicarbonate protocol. Acute kidney injury was assessed by change in serum creatinine and urinary neutrophil‐gelatinase associated lipocalcin (NGAL). Only 1/18 patients (5.5%) developed acute kidney injury as defined by change in serum creatinine 48 hours after contrast exposure. No patients demonstrated significant change in urinary NGAL at 3 or 48 hours after procedure, nor did any require acute initiation of dialysis. Fistulography alone, or with angioplasty, utilizing a low volume of iodinated contrast and sodium bicarbonate solution for prophylaxis, appears to be safe in the CKD stages 4 and 5 population.
The relationship between alloimmunization and posttransfusion granulocyte survival: experience in a chronic granulomatous disease cohort
Authors: Heim K.F. , Fleisher T.A. , Stroncek D.F. , Holland S.M. , Gallin J.I. , Malech H.L. , Leitman S.F. 
Published: December 2010

BACKGROUND: The efficacy of granulocyte transfusions in patients with HLA alloimmunization is uncertain. A flow cytometric assay using dihydrorhodamine 123 (DHR), a marker for cellular NADPH oxidase activity, was used to monitor the differential survival of transfused oxidase‐positive granulocytes in alloimmunized patients with chronic granulomatous disease (CGD).STUDY DESIGN AND METHODS: Ten patients with CGD and serious infections were treated with daily granulocyte transfusions derived from steroid and granulocyte–colony‐stimulating factor–stimulated donors. The proportion of neutrophils with intact oxidase activity was quantitated by DHR fluorescence on samples drawn before and 1 hour after transfusion. The incidence of acute transfusion reactions was correlated with the results of DHR fluorescence and biweekly HLA serologic screening assays.RESULTS: Eight of 10 patients experienced acute adverse reactions in association with granulocyte transfusions. Four had only chills and/or fever, and four experienced respiratory compromise; all eight exhibited HLA alloimmunization. Mean (±SD) oxidase‐positive cell recovery was 19.7 ± 17.4% (n = 15 transfusions) versus 0.95 ± 1.59% (n = 16) in the absence and presence of HLA allosensitization, respectively (p < 0.01). Greater than 1% in vivo recovery of DHR‐enhancing donor granulocytes was strongly correlated with lack of HLA alloimmunization.CONCLUSION: The ability to detect DHR‐positive donor granulocytes by flow cytometry is strongly correlated with absence of HLA alloimmunization and lack of acute reactions to granulocyte transfusions in patients with CGD. If HLA antibodies are present and the survival of donor granulocytes is low by DHR analysis, transfusions should be discontinued, avoiding a therapy associated with high risk and unclear benefit.
A validation study of new cryopreservation bags for implementation in a blood and marrow transplant laboratory
Authors: Pomper Gregory J. , Wilson Emily , Isom Scott , Hurd David D. 
Published: December 2010

BACKGROUND: A new cryopreservation bag for hematopoietic cell transplantation requires validation as a safe alternative to the bag currently being used in the laboratory.STUDY DESIGN AND METHODS: The new bag was validated using both laboratory and clinical criteria. Laboratory validation proceeded using paired samples of mononuclear cells processed using standard procedures. Cells cryopreserved in the new and old bags were compared for viability, cell counts, CD34 enumeration, colony‐forming unit assays, and bag integrity. After completion of laboratory investigations, engraftment with the new bags was followed and compared to historical engraftment using the old bags.RESULTS: There were no significant differences between the old and new bags detected using laboratory studies. Bag integrity was equivalent. The validation data suggested impaired cell function after cryopreservation in the new bags, but there were no significant differences in engraftment potential using either material. Days to engraftment was longer using the new bags, but statistical analysis revealed an association with CD34 dose and not with cryopreservation bag type.CONCLUSION: The new bags were noninferior to the old bags. A change in cryopreservation bag type may appear to affect cell function and potentially affect engraftment. Multiple analyses may be needed to understand the effect of cell processing changes.
Glycine and Taurine Equally Prevent Fatty Livers from Kupffer Cell‐Dependent Injury: AnIn VivoMicroscopy Study
Authors: BRUNS HELGE , WATANPOUR INGO , GEBHARD MARTHA‐MARIA , FLECHTENMACHER CHRISTA , GALLI UWE , SCHULZE‐BERGKAMEN HENNING , ZORN MARKUS , BÜCHLER MARKUS W. , SCHEMMER PETER 
Published: December 2010

Please cite this paper as: Bruns, Watanpour, Gebhard, Flechtenmacher, Galli, Schulze‐Bergkamen, Zorn, Büchler and Schemmer (2011). Glycine and Taurine Equally Prevent Fatty Livers from Kupffer Cell‐Dependent Injury: AnIn VivoMicroscopy Study.Microcirculation 18(3), 205–213.AbstractBackground: IRI still is a major problem in liver surgery due to warm ischemia and organ manipulation. Steatosis is not only induced by diabetes, hyperalimentation, alcohol and toxins, but also chemotherapy given before resection. Since steatotic livers are prone to Kupffer cell‐dependent IRI, protection of steatotic livers is of special interest. This study was designed to compare the effect of taurine and glycine on IRI in steatotic livers.Materials and Methods: Steatosis was induced with ethanol (7 g/kg b.w.; p.o.) in female SD rats. Ten minutes after inactivation of Kupffer cells with taurine or glycine (300 mM; i.v.), left liver lobes underwent 60 minutes of warm ischemia. Controls received the same volume of valine (300 mM; i.v.) or normal saline. After reperfusion, white blood cell‐endothelial interactions and latex‐bead phagocytosis by Kupffer cells were investigated. Liver enzymes were measured to estimate injury. For statistical analysis, ANOVA and Student’st‐test were used.Results: Glycine and taurine significantly decreased leukocyte‐ and platelet‐endothelium interactions and latex‐bead phagocytosis (p < 0.05). Liver enzymes were significantly lower after glycine and taurine (p < 0.05).Conclusions: This study shows that preconditioning with taurine or glycine is equally effective in preventing injury to fatty livers most likely via Kupffer cell‐dependent mechanisms.