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Selected AbstractsOCTN2 is associated with carnitine transport capacity of rat skeletal musclesACTA PHYSIOLOGICA, Issue 1 2010Y. Furuichi Abstract Aim:, Carnitine plays an essential role in fat oxidation in skeletal muscles; therefore carnitine influx could be crucial for muscle metabolism. OCTN2, a sodium-dependent solute carrier, is assumed to transport carnitine into various organs. However, OCTN2 protein expression and the functional importance of carnitine transport for muscle metabolism have not been studied. We tested the hypothesis that OCTN2 is expressed at higher levels in oxidative muscles than in other muscles, and that the carnitine uptake capacity of skeletal muscles depends on the amount of OCTN2. Methods:, Rat hindlimb muscles (soleus, plantaris, and the surface and deep portions of gastrocnemius) were used for Western blotting to detect OCTN2. Tissue carnitine uptake was examined by an integration plot analysis using l -[3H]carnitine as a tracer. Tissue carnitine content was determined by enzymatic cycling methods. The percentage of type I fibres was determined by histochemical analysis. Results:, OCTN2 was detected in all skeletal muscles although the amount was lower than that in the kidney. OCTN2 expression was significantly higher in soleus than in the other skeletal muscles. The amount of OCTN2 was positively correlated with the percentage of type I fibres in hindlimb muscles. The integration plot analysis revealed a positive correlation between the uptake clearance of l -[3H]carnitine and the amount of OCTN2 in skeletal muscles. However, the carnitine content in soleus was lower than that in other skeletal muscles. Conclusion:, OCTN2 is functionally expressed in skeletal muscles and is involved in the import of carnitine for fatty acid oxidation, especially in highly oxidative muscles. [source] The causes, consequences and detection of publication bias in psychiatryACTA PSYCHIATRICA SCANDINAVICA, Issue 4 2000Simon M. Gilbody Objective: Publication bias threatens the validity of published research, although this topic has received little attention in psychiatry. The purpose of this article is to produce a systematic overview of the causes and consequences of publication bias and to summarize the available methods with which it is detected and corrected. Method: Empirical evidence for the existence of publication bias is reviewed and the following methods are applied to an illustrative case example from psychiatry: funnel plot analysis; the ,file drawer method'; linear regression techniques; rank correlation; ,trim and fill'. Results: Small studies are particularly susceptible to publication and related bias. All methods to detect publication bias depend upon the availability of a number of individual studies with a range of sample sizes. Unfortunately, large numbers of studies of varying sample size are not always available in many areas of psychiatric research. Conclusion: Where possible researchers should always test for the presence of publication bias. The problem of publication bias will not be solved by anything other than a prospective trials register. [source] Native and subunit molecular mass and quarternary structure of the hemoglobin from the primitive branchiopod crustacean Triops cancriformisFEBS JOURNAL, Issue 17 2006Morgane Rousselot Many branchiopod crustaceans are endowed with extracellular, high-molecular-weight hemoglobins whose exact structural characteristics have remained a matter of conjecture. By using a broad spectrum of techniques, we provide precise and coherent information on the hemoglobin of one of the phylogenetically ,oldest' extant branchiopods, the tadpole shrimp Triops cancriformis. The hemoglobin dissociated under reducing conditions into two subunits, designated TcHbA and TcHbB, with masses of 35 775 ± 4 and 36 055 ± 4 Da, respectively, determined by ESI-MS. Nonreducing conditions showed only two disulfide-bridged dimers, a homodimer of TcHbA, designated D1 (71 548 ± 5 Da), and the heterodimer D2 (71 828 ± 5 Da). Carbamidomethylation of free SH groups revealed the presence of three cysteines per subunit and indicated one intrasubunit and one intersubunit disulfide bridge. Ultracentrifugation and light-scattering experiments under nondenaturating conditions yielded mass estimates that suggested an uneven number of 17 subunits forming the native hemoglobin. This unrealistic number resulted from the presence of two size classes (16-mer and 18-mer), which were recognized by native PAGE and Ferguson plot analysis. ESI-MS revealed three hemoglobin isoforms with masses of 588.1 kDa, 662.0 kDa, and 665.0 kDa. The 16-mer and the smaller 18-mer species are supposed to be composed of TcHbA only, given the dominance of this subunit type in SDS/PAGE. Transmission electron microscopy of negatively stained specimens showed a population of compact molecules with geometrical extensions of 14, 16 and 9 nm. The proposed stoichiometric model of quarternary structure provides the missing link to achieve a mechanistic understanding of the structure,function relationships among the multimeric arthropodan hemoglobins. [source] Comparison of different methodologies for CD4 estimation in a clinical settingHIV MEDICINE, Issue 4 2008S Jeganathan Objective To compare flow cytometry assays, using traditional dual platform (DP) or newer single platform (SP) for CD4 enumeration. Method Records of subjects enrolled in four separate clinical trials using the same central laboratory [SP methodology (Trucount)] were reviewed retrospectively. Eighteen subjects had 60 matching contemporaneous samples at multiple timepoints. Results DP flow cytometry yielded higher CD4 counts in 50/60 assays (83%). CD4 count and percentage by the two methods showed strong correlation for the counts (r=0.965, P<0.0001) and percentages (r=0.959, P<0.0001). Bland,Altman plot analysis showed that the limits of variation were within agreeable limits of ±2SD in 56/60 (93.3%) samples tested. Twenty-five (42%) samples had a difference of >50 cells/,L. Of these six (24%) exceeded 100 cells. Conclusion This study is in agreement with previous reports of strong correlation between DP and SP flow cytometry. This review found differences in CD4 counts in a high proportion of samples tested highlighting the importance for clinicians to be aware of such differences when interpreting results from the two methods. [source] Effects of zotepine and olanzapine on noradrenaline transporter in cultured bovine adrenal medullary cellsHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 7 2005Reiji Yoshimura Abstract Background Previously, it was demonstrated that the inhibitory effects of atypical antipsychotic drugs such as clozapine and risperidone on noradrenaline transporter (NAT) might in part be associated with their clinical profile. The present study examined the effects of zotepine on NAT in the cells and compared them with those of olanzapine. Materials and Methods Adrenal medullary cells were isolated by a method of collagenase digestion of slices of fresh bovine adrenal medulla and the cells were plated at a density of 4,×,106 cells. Cells were incubated with [3H]noradrenaline (NA) in the presence or absence of zotepine or olanzapine. The amount of radioactivity taken into the cells was counted by a liquid scintillation counter. Plasma membranes of bovine adrenal medulla were prepared, and the binding of [3H]desipramine (DMI) was determined by incubating the membrane suspension in binding buffer together with zotepine or olanzapine. Specific binding of [3H] DMI was defined as that binding which was inhibited by nisoxetine. Results Both zotepine (10,1000,ng/ml) and olanzapine (10,1000,ng/ml) decreased [3H]NA uptake in a concentration-dependent manner. The IC50 values of zotepine and olanzapine on [3H]NA uptake were 10,±,4 and 14,±,8,ng/ml, respectively. Eadie-Hofstee analysis of [3H]NA uptake showed that treatment with zotepine and olanzapine decreased the Vmax of uptake without changing the Km. Both zotepine (10,1000,ng/ml) and olanzapine (30,1000,ng/ml) inhibited [3H]DMI binding in a concentration-dependent manner. The IC50 values of zotepine and olanzapine on [3H]DMI binding were 50,±,18, and 120,±,38,ng/ml, respectively. Scatchard plot analysis of [3H]DMI binding showed that zotepine and olanzapine decreased the Bmax of binding without altering the Kd. Conclusions The inhibitory effects of zotepine and olanzapine might be responsible in part for their clinical profile. Copyright © 2005 John Wiley & Sons, Ltd. [source] Evaluation of a new automated enzyme fluoroimmunoassay using recombinant plasmid dsDNA for the detection of anti-dsDNA antibodies in SLEJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 5 2002D. Villalta Abstract ELISA methods to detect anti-double-stranded DNA (anti-dsDNA) antibodies are highly sensitive, but are less specific for the diagnosis of SLE than the immunofluorescence test on Crithidia luciliae (CLIFT) and the Farr assay because they also detect low-avidity antibodies. This study evaluated the specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of a new automated fluoroimmunoassay (EliA dsDNA; Pharmacia, Freiburg, Germany). We compared the results with those obtained using a commercial CLIFT and an in-house anti-dsDNA IgG ELISA method, and verified its putative ability to detect only high-avidity anti-dsDNA antibodies. Sera from 100 SLE patients and 120 controls were studied. The control group included 20 healthy donors, 70 patients with other rheumatic diseases (32 systemic sclerosis (SSc); 18 primary Sjögren syndrome (pSS), 20 rheumatoid arthritis (RA)), and 30 patients with various infectious diseases (ID). Anti-dsDNA avidity was estimated using an ELISA method based upon the law of mass action, and a simplified Scatchard plot analysis for data elaboration; the apparent affinity constant (Kaa) was calculated and expressed as arbitrary units (L/U). Sensitivity, specificity, PPV, and NPV for SLE were 64%, 95.8%, 93.8% and 72.7%, respectively, for the EliA anti-dsDNA assay; 55%, 99.2%, 98.5%, and 68.8%, respectively, for the CLIFT; and 64%, 93.3%, 90.6%, and 72.3%, respectively, for the in-house ELISA. Although EliA anti-dsDNA was positive mainly in SLE patients with high- (Kaa>80 L/U) and intermediate- (Kaa 30,80 L/U) avidity antibodies (45.3% and 49.9%, respectively), it was also positive in five (7.8%) SLE patients with low-avidity anti-dsDNA antibodies, and five controls (three SSc, one pSS, and one ID) (mean Kaa = 16.4 ± 9.04 L/U). In conclusion, EliA anti-dsDNA assay showed a higher sensitivity than the CLIFT, and a good specificity and PPV for SLE. Its putative ability to detect only high-avidity anti-dsDNA antibodies remains questionable. J. Clin. Lab. Anal. 16:227,232, 2002. © 2002 Wiley-Liss, Inc. [source] Anomeric information obtained from a series of synthetic trisaccharides using energy resolved mass spectraJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 6 2007Shusaku Daikoku Abstract The majority of structural investigations of oligosaccharides based on mass spectrometry use naturally occurring oligosaccharides, which do not allow extracting any common feature associated with anomeric structures and linkage positions. In order to address the issue to find such characteristics possibly contained in oligosaccharide structure, a synthetic combinatorial trisaccharide library was analyzed. The trisaccharides used in the analysis consisted of L -fucose, D -galactose and D -glucose, in which individual glycosidic linkages existed in either ,- or ,-anomers. The analysis of energy-resolved mass spectra (ERMS) and the scattered plot analysis of some parameters obtained from ERMS for a series of trisaccharides revealed that lower activation energy was required for the dissociation of ,-glycosides of these sugars compared to those of the corresponding ,-anomers. It is suggested that this finding may be useful in structural analysis of natural oligosaccharides. Copyright © 2007 John Wiley & Sons, Ltd. [source] Detection of human sapovirus by real-time reverse transcription-polymerase chain reactionJOURNAL OF MEDICAL VIROLOGY, Issue 10 2006Tomoichiro Oka Abstract Sapovirus (SaV) is an agent of gastroenteritis for humans and swine, and is divided into five distinct genogroups (GI,GV) based on its capsid gene sequences. Typical methods of SaV detection include electron microscopy (EM), enzyme-linked immunosorbent assay (ELISA), and reverse transcription-polymerase chain reaction (RT-PCR). A novel TaqMan-based real-time RT-PCR assay was developed that is sensitive and has the ability to detect the broad range of genetically diverse human SaV strains. A nucleotide alignment of 10 full-length SaV genome sequences was subjected to similarity plot analysis, which indicated that the most conserved site was the polymerase-capsid junction in open reading frame 1 (ORF1). Based on multiple alignments of the 27 available sequences encoding this junction, we designed sets of primers and TaqMan MGB probes that detect human SaV GI, GII, GIV, and GV sequences in a single tube. The reactivity was confirmed with SaV GI, GII, GIV, and GV control plasmids, and the efficiency ranged from 2.5,×,107 to 2.5,×,101 copies per tube. Analysis using clinical stool specimens revealed that the present system was capable of detecting SaV GI, GII, GIV, and GV sequences, and no cross-reactivity was observed against other enteric viruses, including norovirus (NoV), rotavirus, astrovirus, and adenovirus. This is the first real-time RT-PCR system that could detect all genogroups of human sapoviruses. J. Med. Virol. 78:1347,1353, 2006. © 2006 Wiley-Liss, Inc. [source] Quantitative analysis of first-pass contrast-enhanced myocardial perfusion MRI using a patlak plot method and blood saturation correctionMAGNETIC RESONANCE IN MEDICINE, Issue 2 2009Takashi Ichihara Abstract The objectives of this study were to develop a method for quantifying myocardial K1 and blood flow (MBF) with minimal operator interaction by using a Patlak plot method and to compare the MBF obtained by perfusion MRI with that from coronary sinus blood flow in the resting state. A method that can correct for the nonlinearity of the blood time,signal intensity curve on perfusion MR images was developed. Myocardial perfusion MR images were acquired with a saturation-recovery balanced turbo field-echo sequence in 10 patients. Coronary sinus blood flow was determined by phase-contrast cine MRI, and the average MBF was calculated as coronary sinus blood flow divided by left ventricular (LV) mass obtained by cine MRI. Patlak plot analysis was performed using the saturation-corrected blood time,signal intensity curve as an input function and the regional myocardial time,signal intensity curve as an output function. The mean MBF obtained by perfusion MRI was 86 ± 25 ml/min/100 g, showing good agreement with MBF calculated from coronary sinus blood flow (89 ± 30 ml/min/100 g, r = 0.74). The mean coefficient of variation for measuring regional MBF in 16 LV myocardial segments was 0.11. The current method using Patlak plot permits quantification of MBF with operator interaction limited to tracing the LV wall contours, registration, and time delays. Magn Reson Med, 2009. © 2009 Wiley-Liss, Inc. [source] Concomitant polymorphic behavior of di-,-thiocyanato-,2N:S;,2S:N -bis[bis(tri- p -fluorophenylphosphine-,P)silver(I)]ACTA CRYSTALLOGRAPHICA SECTION B, Issue 1 2010Bernard Omondi The structures of two polymorphs, both monoclinic P21/n [polymorph (I)] and P21/c [polymorph (II)], of di-,-thiocyanato-,2N:S;,2S:N -bis[bis(tri- p -fluorophenylphosphine-,P)silver(I)] complexes have been determined at 100,K. In both polymorphs the complex has a dinuclear structure where the silver(I) coordinates to two phosphine ligands and two bridging thiocyanate anions to form complexes with distorted tetrahedral geometry. Polymorph (I) has just one half of the [Ag2(SCN)2{P(4-FC6H4)3}4] molecule at (0, ½, 0) from the origin in the asymmetric unit. Polymorph (II) has one and a half molecules of [Ag2(SCN)2{P(4-FC6H4)3}4] in the asymmetric unit; the half molecule is situated at (0, 1, ½), while the full molecule is located at (1/3, ½, 1/3) from the origin. The Ag,P bond distances range from 2.4437,(4) to 2.4956,(7),Å in both polymorphs. The Ag,S distances are 2.5773,(7),Å in (I) and 2.5457,(5), 2.5576,(5) and 2.5576,(5),Å in (II). The full molecule in polymorph (II) has slightly shorter Ag,N bond distances [2.375,(1) and 2.367,(2),Å] compared with the half molecules in both polymorphs [2.409,(2),Å in (II) and 2.395,(2),Å in (I)]. The two polymorphs are compared using r.m.s. overlay calculations as well as half-normal probability plot analysis. [source] Isomorphism in monomeric 1:3 complexes of silver(I) salts with tri- p -tolylphosphineACTA CRYSTALLOGRAPHICA SECTION B, Issue 6 2009Bernard Omondi Reaction of silver(I) salts with three equivalents of tri- p -tolylphosphine in CH3CN resulted in a series of isomorphous complexes [AgX{P(4-MeC6H4)3}3] (X = Br, SCN, ClO4). These complexes all crystallize in the orthorhombic space group Pna21. The complexes with X = Br, SCN are distorted tetrahedral around the silver(I) atom, whereas the ClO4, complex is distorted trigonal planar around the silver. The new complexes are compared with each other using r.m.s. overlay calculations as well as half-normal probability plot analysis and with the previously reported isomorphous chloride, bromide as well as the non-isomorphous iodide complexes. [source] Intermethod Reliability of Real-time Versus Delayed Videotaped Evaluation of a High-fidelity Medical Simulation Septic Shock ScenarioACADEMIC EMERGENCY MEDICINE, Issue 9 2009Justin B. Williams MD Abstract Objectives:, High-fidelity medical simulation (HFMS) is increasingly utilized in resident education and evaluation. No criterion standard of assessing performance currently exists. This study compared the intermethod reliability of real-time versus videotaped evaluation of HFMS participant performance. Methods:, Twenty-five emergency medicine residents and one transitional resident participated in a septic shock HFMS scenario. Four evaluators assessed the performance of participants on technical (26-item yes/no completion) and nontechnical (seven item, five-point Likert scale assessment) scorecards. Two evaluators provided assessment in real time, and two provided delayed videotape review. After 13 scenarios, evaluators crossed over and completed the scenarios in the opposite method. Real-time evaluations were completed immediately at the end of the simulation; videotape reviewers were allowed to review the scenarios with no time limit. Agreement between raters was tested using the intraclass correlation coefficient (ICC), with Cronbach's alpha used to measure consistency among items on the scores on the checklists. Results:, Bland-Altman plot analysis of both conditions revealed substantial agreement between the real-time and videotaped review scores by reviewers. The mean difference between the reviewers was 0.0 (95% confidence interval [CI] = ,3.7 to 3.6) on the technical evaluation and ,1.6 (95% CI = ,11.4 to 8.2) on the nontechnical scorecard assessment. Comparison of evaluations for the videotape technical scorecard demonstrated a Cronbach's alpha of 0.914, with an ICC of 0.842 (95% CI = 0.679 to 0.926), and the real-time technical scorecard demonstrated a Cronbach's alpha of 0.899, with an ICC of 0.817 (95% CI = 0.633 to 0.914), demonstrating excellent intermethod reliability. Comparison of evaluations for the videotape nontechnical scorecard demonstrated a Cronbach's alpha of 0.888, with an ICC of 0.798 (95% CI = 0.600 to 0.904), and the real-time nontechnical scorecard demonstrated a Cronbach's alpha of 0.833, with an ICC of 0.714 (95% CI = 0.457 to 0.861), demonstrating substantial interrater reliability. The raters were consistent in agreement on performance within each level of training, as the analysis of variance demonstrated no significant differences between the technical scorecard (p = 0.176) and nontechnical scorecard (p = 0.367). Conclusions:, Real-time and videotaped-based evaluations of resident performance of both technical and nontechnical skills during an HFMS septic shock scenario provided equally reliable methods of assessment. [source] A new class of potent matrix metalloproteinase 13 inhibitors for potential treatment of osteoarthritis: Evidence of histologic and clinical efficacy without musculoskeletal toxicity in rat modelsARTHRITIS & RHEUMATISM, Issue 7 2009Vijaykumar M. Baragi Objective Matrix metalloproteinases (MMPs) have long been considered excellent targets for osteoarthritis (OA) treatment. However, clinical utility of broad-spectrum MMP inhibitors developed for this purpose has been restricted by dose-limiting musculoskeletal side effects observed in humans. This study was undertaken to identify a new class of potent and selective MMP-13 inhibitors that would provide histologic and clinical efficacy without musculoskeletal toxicity. Methods Selectivity assays were developed using catalytic domains of human MMPs. Freshly isolated bovine articular cartilage or human OA cartilage was used in in vitro cartilage degradation assays. The rat model of monoiodoacetate (MIA),induced OA was implemented for assessing the effects of MMP-13 inhibitors on cartilage degradation and joint pain. The surgical medial meniscus tear model in rats was used to evaluate the chondroprotective ability of MMP-13 inhibitors in a chronic disease model of OA. The rat model of musculoskeletal side effects (MSS) was used to assess whether selective MMP-13 inhibitors have the joint toxicity associated with broad-spectrum MMP inhibitors. Results A number of non,hydroxamic acid,containing compounds that showed a high degree of potency for MMP-13 and selectivity against other MMPs were designed and synthesized. Steady-state kinetics experiments and Lineweaver-Burk plot analysis of rate versus substrate concentration with one such compound, ALS 1-0635, indicated linear, noncompetitive inhibition, and Dixon plot analysis from competition studies with a zinc chelator (acetoxyhydroxamic acid) and ALS 1-0635 demonstrated nonexclusive binding. ALS 1-0635 inhibited bovine articular cartilage degradation in a dose-dependent manner (48.7% and 87.1% at 500 nM and 5,000 nM, respectively) and was effective in inhibiting interleukin-1,, and oncostatin M,induced C1,C2 release in human OA cartilage cultures. ALS 1-0635 modulated cartilage damage in the rat MIA model (mean ± SEM damage score 1.3 ± 0.3, versus 2.2 ± 0.4 in vehicle-treated animals). Most significantly, when treated twice daily with oral ALS 1-0635, rats with surgically induced medial meniscus tear exhibited histologic evidence of chondroprotection and reduced cartilage degeneration, without observable musculoskeletal toxicity. Conclusion The compounds investigated in this study represent a novel class of MMP-13 inhibitors. They are mechanistically distinct from previously reported broad-spectrum MMP inhibitors and do not exhibit the problems previously associated with these inhibitors, including selectivity, poor pharmacokinetics, and MSS liability. MMP-13 inhibitors exert chondroprotective effects and can potentially modulate joint pain, and are, therefore, uniquely suited as potential disease-modifying osteoarthritis drugs. [source] Inconsistency of Reported Uremic Toxin ConcentrationsARTIFICIAL ORGANS, Issue 8 2007Natalie Meert Abstract:, Discrepancies in reported uremic toxin concentrations were evaluated for 78 retention solutes. For this analysis, 378 publications were screened. Up to eight publications per toxin were retained. The highest and the lowest reported concentrations, as well as the median reported concentration were registered. The ratio between the highest and the lowest (H/L) concentrations and, for some solutes, also the ratio between the highest and the median (H/M) concentrations were calculated. The compounds were arbitrarily subdivided into three groups based on their H/L ratio: group A, H/L < 3 (n = 33); group B, 3 < H/L < 8.5 (n = 20); and group C, H/L > 8.5 (n = 25). Solutes of groups A and B showed a low to intermediate scatter, suggesting a homogeneity of reported data. Group C showed a more substantial scatter. For at least 10 compounds of group C, extremely divergent concentrations were registered (H/M > 5.5) using scatter plot analysis. For all solutes of groups A and B, the highest reported concentration could be used as a reference. For some solutes of group C and for the compounds showing a divergent scatter analysis, however, more refined directives should be followed. [source] Mechanism of tyrosinase inhibition by deoxyArbutin and its second-generation derivativesBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2008S. Chawla Summary Background, Disorders, such as age spots, melasma and hyperpigmentation at sites of actinic damage, emanate from the augmentation of an increased amount of epidermal melanin. Objectives, The ineptness of current therapies in treating these conditions, as well as high cytotoxicity, mutagenicity, poor skin penetration and low stability of skin-depigmenting formulations led us to investigate new compounds that meet the medical requirements for depigmentation agents. We have shown previously that the tyrosinase inhibitor deoxyArbutin (dA) is a more effective and less toxic skin lightener than hydroquinone (HQ). Methods, The efficacy and reversibility of dA and its derivatives on inhibiting tyrosine hydroxylase and DOPAoxidase was assessed using standard assays. Results, dA and its second-generation derivatives inhibit tyrosine hydroxylase and DOPAoxidase activities of tyrosinase dose dependently thereby inhibiting melanin synthesis in intact melanocytes, when used at concentrations that retain 95% cell viability in culture. This depigmenting effect was completely reversible when the compounds were removed. Tyrosinase inhibition was also observed in vitro when tested using human and purified mushroom tyrosinase, establishing that they are direct enzyme inhibitors. Lineweaver,Burk reciprocal plot analysis using mushroom tyrosinase illustrated that dA and its derivatives are more robust competitive inhibitors than HQ, when tyrosine is used as substrate. Conclusions, Thus, dA and its second-generation derivatives, which inhibit melanogenesis at safe concentrations by specifically acting on the tyrosinase enzyme at a post-translational level, are promising agents to ameliorate hyperpigmented lesions or lighten skin. [source] Transglutaminase differentially regulates growth signalling in rat perivenous and periportal hepatocytesCELL PROLIFERATION, Issue 3 2006A. Maruko PPH and PVH subpopulations have been isolated using the digitonin/collagenase perfusion technique. DNA synthesis was assessed by [3H] thymidine incorporation into hepatocytes. The assay for binding of [125I] EGF to cultured hepatocytes was analysed by Scatchard plot analysis. Pretreatment with the TG2 inhibitor monodansylcadaverine (MDC) greatly increased EGF-induced DNA synthesis in both PPH and PVH. Furthermore, [125I] EGF binding studies in PVH treated with MDC indicated that high-affinity EGF receptor expression was markedly up-regulated, whereas in PPH, there was no significant effect. Treatment with retinoic acid (RA), an inducer of TG2 expression, significantly decreased EGF-induced DNA synthesis in both PPH and PVH. Binding studies in the presence of RA revealed that the high-affinity EGF receptor was down-regulated and completely absent in both PPH and PVH. These results suggest that TG2 was involved in the differential growth capacities of PPH and PVH through down-regulation of high-affinity EGF receptors. [source] ,-Adrenoceptor agonists for the treatment of vasovagal syncope: a meta-analysis of worldwide published dataACTA PAEDIATRICA, Issue 7 2009Ying Liao Abstract Aim:, The present study was aimed at evaluating present randomized controlled trials (RCTs) regarding the effect of ,-adrenoceptor agonists on vasovagal syncope (VVS). Methods:, According to inclusion and exclusion criteria, articles were selected from medical electronic databases. RCTs were then assessed based on the Juni assessment, and meta-analysis was completed using the Review Manager 4.2 software. Indication to further evaluate effects was the recurrence of syncope during follow-up treatment or a response in the head-up tilt test (HUT) after treatment. The results were stated as odd ratio (OR), with a 95% confidence interval (CI) and a p < 0.05 significant level. Results:, In total, six RCTs were selected. Funnel plot analysis showed possible publication bias. Meta-analysis of the six RCTs, including all 165 patients in the treatment group and 164 patients in the control group, indicated that ,-adrenoceptor agonists were more effective than placebos in treating VVS (OR = 0.21, 95% CI: 0.06,0.77, p = 0.02). The further, weighted independent t- test disclosed that the weighted mean percentage of responders for midodrine (76.3%± 7.7%) was significantly higher than that for etilefrine (65.5%± 15.4%) (t = 5.863, p < 0.001). Conclusion:, The currently published RCTs support that ,-adrenoceptor agonists might be effective for VVS. Midodrine can be regarded as a better choice compared with etilefrine. [source] Decrease in heart rate variability with overtraining: assessment by the Poincaré plot analysisCLINICAL PHYSIOLOGY AND FUNCTIONAL IMAGING, Issue 1 2004Laurent Mourot Summary Numerous symptoms have been associated with the overtraining syndrome (OT), including changes in autonomic function. Heart rate variability (HRV) provides non-invasive data about the autonomic regulation of heart rate in real-life conditions. The aims of the study were to: (i) characterize the HRV profile of seven athletes (OA) diagnosed as suffering of OT, compared with eight healthy sedentary (C) and eight trained (T) subjects during supine rest and 60° upright, and (ii) compare the traditional time- and frequency-domain analysis assessment of HRV with the non-linear Poincaré plot analysis. In the latter each R-R interval is plotted as a function of the previous one, and the standard deviations of the instantaneous (SD1) and long-term R-R interval variability are calculated. Total power was higher in T than in C and OA both in supine (1158 ± 1137, 6092 ± 3554 and 2970 ± 2947 ms2 for C, T and OA, respectively) and in upright (640 ± 499, 1814 ± 806 and 1092 ± 712 ms2 for C, T and OA, respectively; P<0·05) positions. In supine position, indicators of parasympathetic activity to the sinus node were higher in T compared with C and OA (high-frequency power: 419·1 ± 381·2, 1105·3 ± 781·4 and 463·7 ± 715·8 ms2 for C, T and OA, respectively; P<0·05; SD1: 29·5 ± 18·5, 75·2 ± 17·2 and 37·6 ± 27·5 for C, T and OA, respectively; P<0·05). OA had a marked predominance of sympathetic activity regardless of the position (LF/HF were 0·47 ± 0·35, 0·47 ± 0·50 and 3·96 ± 5·71 in supine position for C, T and OA, respectively, and 2·09 ± 2·17, 7·22 ± 6·82 and 12·04 ± 10·36 in upright position for C, T and OA, respectively). The changes in HRV indexes induced by the upright posture were greater in T than in OA. The shape of the Poincaré plots allowed the distinction between the three groups, with wide and narrow shapes in T and OA, respectively, compared with C. As Poincaré plot parameters are easy to compute and associated with the ,width' of the scatter gram, they corroborate the traditional time- and frequency-domain analysis. We suggest that they could be used to indicate fatigue and/or prevent OT. [source] Meta analysis of the treatment-related factors of external apical root resorptionORTHODONTICS & CRANIOFACIAL RESEARCH, Issue 2 2004GR Segal Structured Abstract Authors , Segal GR, Schiffman PH, Tuncay OC Objective , To elucidate possible treatment-related etiological factors , such as, duration of treatment and apical displacement , for external root resorption. Design , Meta-analysis of the available English-language literature. Inclusion & Exclusion Criteria , Papers with a sample size >10, fixed appliances, pre- and post-operative radiographs, and apical displacement recorded were included. History of trauma, prior root resorption and endodontic treatment were excluded. Appropriateness of these selections was tested with a ,funnel plot' analysis. Outcome Measure , Correlations between root resorption, apical displacement, and treatment duration. Results , Mean apical root resorption was strongly correlated with total apical displacement (r = 0.822) and treatment duration (r = 0.852). Conclusion , The treatment-related causes of root resorption appear to be the total distance the apex had moved and the time it took. [source] | ||||||||||||||||