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Intrinsic Defects (intrinsic + defect)
Selected AbstractsIs postprandial hypertriglyceridaemia in relatives of type 2 diabetic subjects a consequence of insulin resistance?EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2005A. Kriketos Abstract Background, Higher postprandial triglyceride responses reported in first degree relatives of people with type 2 diabetes (REL) were postulated to be the result of an early, possibly intrinsic, defect in oral lipid handling. The postprandial triglyceride response to high fat meals (HFM) in normal subjects is reduced by the insulin response to dietary carbohydrate (CHO) in the meal. The aims of this study were to examine whether (1) insulin resistance is associated with an intrinsic defect in triglyceride handling in insulin-resistant REL and (2) insulin resistance is associated with altered triglyceride handling after HFM with high CHO content. Materials and methods, Postprandial responses to a HFM in normolipidaemic, normoglycaemic REL were compared with subjects without a family history of diabetes mellitus (CON). Over 6 h, the insulin, glucose, triglyceride and nonesterified fatty acid (NEFA) responses after a high fat (80 g fat), low CHO (HFM-LC; 20 g CHO, 4250 kJ) meal and a high fat, high CHO (HFM-HC; 100 g CHO, 5450 kJ) meal were examined. Results, The 10 (7F/3M) REL were significantly more insulin-resistant, determined by glucose infusion during a hyperinsulinaemic euglycaemic clamp than the 10 (5F/5M) CON (glucose infusion rate 44·6 ± 4·9 vs. 60·0 ± 4·8 µmol min,1 kg FFM,1, P = 0·037). Subjects were similar for age and body mass index (BMI). The triglyceride increments after the HFM-LC were similar in both, peaking at 180,240 min (,0·77 ± 0·11 mmol L,1), demonstrating no postprandial defect in REL, despite insulin resistance. There was a significantly lower postprandial triglyceride response in CON following the HFM-HC compared with the HFM-LC, but not in REL. In contrast, the higher insulin level during the HFM-HC was associated with significantly greater NEFA level suppression than in the HFM-LC (2·13 ± 0·51 vs. 0·70 ± 0·35 mmol L,1, P = 0·03), only in the REL. Conclusions, These results are inconsistent with a primary aetiological role for postprandial hypertriglyceridaemia in already insulin resistant type 2 diabetic REL, but raise the possibility that this potentially atherogenic manifestation is secondary to insulin resistance lessening VLDL production and/or release from the liver. [source] Aging does not reduce the hepatocyte proliferative response of mice to the primary mitogen TCPOBOPHEPATOLOGY, Issue 4 2004Giovanna M. Ledda-Columbano It has been shown that the magnitude of DNA synthesis and the time at which maximal DNA synthesis occurs after two-thirds partial hepatectomy (PH) is greatly reduced in the liver of aged rodents compared to young animals. This reduction could represent an intrinsic defect in proliferation or a more specialized change in the response to PH. We therefore evaluated the proliferative capacity of hepatocytes in aged animals, following treatment with primary liver mitogens. We show that treatment of 12-month-old CD-1 mice with the hepatomitogen 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) caused an increase in hepatocyte proliferation similar to that seen in young (8-week-old) mice. The labeling index was 82% in the livers of aged mice versus 76% in young animals. Histological observation demonstrated that the number of hepatocytes entering mitoses was similar in both groups; the mitotic indices were 2.5 per thousand and 2.7 per thousand, respectively. Additional experiments showed that the timing of DNA synthesis and M phase were nearly identical in both aged and young mice. Stimulation of hepatocyte DNA synthesis was associated with increased expression of several cell cycle-associated proteins (cyclin D1, cyclin A, cyclin B1, E2F, pRb, and p107); all were comparable in aged mice and young mice. TCPOBOP treatment also increased expression of the Forkhead Box transcription factor m1b (Foxm 1b) to a similar degree in both groups. In conclusion, hepatocytes retain their proliferative capacity in old age despite impaired liver regeneration. These findings suggest that therapeutic use of mitogens would alleviate the reduction in hepatocyte proliferation observed in the elderly. (Hepatology 2000;40:981,988). [source] Is insulin resistance caused by defects in insulin's target cells or by a stressed mind?DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2005Jonas Burén Abstract The importance of understanding insulin action is emphasized by the increasing prevalence of insulin resistance in various populations and by the fact that it plays an important pathophysiological role in many common disorders, for example, diabetes, obesity, hypertension and dyslipidemia. The primary factors responsible for the development of insulin resistance are so far unknown, although both genetic and environmental factors are involved. The genetic defects responsible for the common forms of insulin resistance, for example, in type 2 diabetes, are largely unidentified. Some studies from our group as well as by other investigators suggest that cellular insulin resistance is reversible and that it may be secondary to factors in the in vivo environment. These may include insulin-antagonistic action of hormones like catecholamines, glucocorticoids, sex steroids and adipokines as well as dysregulation of autonomic nervous activity and they could contribute to the early development of insulin resistance. Some of these factors can directly impair glucose uptake capacity and this might be due to alterations in key proteins involved in insulin's intracellular signaling pathways. This article briefly summarizes proposed mechanisms behind cellular and whole-body insulin resistance. In particular, we question the role of intrinsic defects in insulin's target cells as primary mechanisms in the development of insulin resistance in type 2 diabetes and we suggest that metabolic and neurohormonal factors instead are the main culprits. Copyright © 2005 John Wiley & Sons, Ltd. [source] Altered distribution of natural killer cell subsets identified by CD56, CD27 and CD70 in primary and chronic human immunodeficiency virus-1 infectionIMMUNOLOGY, Issue 2 2008Kehmia Titanji Summary Human natural killer (NK) (CD3, CD56+) cells can be divided into two functionally distinct subsets, CD3, CD56dim and CD3, CD56bright. We analysed the distribution of NK cell subsets in primary and chronic human immunodeficiency virus-1 (HIV-1) infection, to determine if HIV infection stage may influence the subset distribution. In primary infection, contrary to chronic infection, the CD3, CD56dim subset was expanded compared to healthy controls. We also studied the effect of antiretroviral therapy administered early in infection and found that NK cell subset distribution was partially restored after 6 months of antiretroviral therapy in primary infection, but not normalized. Recently, NK cells have been divided into CD27, and CD27+ subsets with different migratory and functional capacity and CD27-mediated NK cell activation has been described in mice. We therefore investigated whether CD27 and/or CD70 (CD27 ligand) expression on NK cells, and thus the distribution of these novel NK subsets, was altered in HIV-1-infected patients. We found up-regulated expression of both CD27 and CD70 on NK cells of patients, resulting in higher proportions of CD27high and CD70high NK cells, and this phenomenon was more pronounced in chronic infection. Experiments conducted in vitro suggest that the high interleukin-7 levels found during HIV-1 infection may participate in up-regulation of CD70 on NK cell subsets. Imbalance of NK cell subsets and up-regulated expression of CD27 and CD70 initiated early in HIV-1 infection may indicate NK cell activation and intrinsic defects initiated by HIV-1 to disarm the innate immune response to the virus. [source] 2D mapping of the response of CVD diamond X-ray detectors: defects and device dynamicsPHYSICA STATUS SOLIDI (A) APPLICATIONS AND MATERIALS SCIENCE, Issue 11 2004M. J. Guerrero Abstract To investigate the influence of intrinsic defects in polycrystalline CVD diamond, we have used a micro-focused X-ray beam to induce local photo-currents in solid state ionisation chambers. The device behaviour was studied as a function of the defect level populations. This microscopic study of the X-ray sensitivity was then performed using varying initial states of the devices as well as varying device temperatures. These measurements, coupled with the study of the temporal evolution of the photocurrent as a function of the temperature, seemed to demonstrate the existence of highly localised regions that may detrimentally affect the overall device response. This may demonstrate that the imperfections CVD diamond devices exhibit may be caused by extremely localised point defects. (© 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Electron paramagnetic resonance and electron-nuclear double resonance of nonequivalent Yb3+ centers in stoichiometric lithium niobatePHYSICA STATUS SOLIDI (B) BASIC SOLID STATE PHYSICS, Issue 1 2009Galina Malovichko Abstract Lithium niobate crystals doped with ytterbium were studied using Electron Paramagnetic Resonance (EPR) and Electron Nuclear Double Resonance (ENDOR). The tremendous narrowing of EPR lines in nearly stoichiometric samples, when compared to those in congruent samples, allowed us to distinguish nine non-equivalent centers, as well as line splitting caused by the hyperfine interaction of ytterbium electrons with the nuclear spins of two magnetic isotopes, 171Yb and 173Yb. Eight of the nine centers are described for the first time. It was found that three of the centers have axial C3 symmetry, and all others have the lowest C1 symmetry due to the presence of intrinsic defects and/or charge compensation defects in the near neighborhood of Yb3+. Characteristics of the g -tensor for all of the centers and hyperfine tensors for axial centers were determined. The ENDOR observations of Nb nuclei in the nearest neighborhood of Yb13+ gave direct evidence that the dominated axial Yb1 center has no charge compensator in its nearest surroundings (distant charge compensation mechanism). Both the EPR and ENDOR data for the main axial ytterbium center are explained by a supposition that Yb3+ ions substitute for Li+. Possible models for low-symmetry centers are discussed. The obtained numerous spectroscopic parameters can be used as cornerstones for model calculations of Yb3+ centers in lithium niobate. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Identification of intrinsic defects in SiC: Towards an understanding of defect aggregates by combining theoretical and experimental approachesPHYSICA STATUS SOLIDI (B) BASIC SOLID STATE PHYSICS, Issue 7 2008Michel Bockstedte Abstract In SiC, mobile point defects may form thermally stable clusters and aggregates, such as di-vacancies or carbon interstitial complexes. Although predicted by theory, experimental evidence of such clusters became available only recently. Combining theoretical and experimental approaches, the unique identification of the di-vacancy, the carbon vacancy-antisite complex with the spin resonance centers P6/P7 and SI5 was recently achieved. In this way also the di-carbon and tri-carbon antisites with the photoluminiscence centers P,T and U, HT3 and HT4, respectively were identified. The two identified vacancy complexes show distinct properties: while the di-vacancy, like the silicon vacancy possesses a high-spin ground state, the carbon vacancy,antisite complex, like the carbon vacancy, is a Jahn,Teller center. These effects consistently explain the complex properties of the spin resonance spectra and are discussed in detail for the isolated vacancies. The aggregation of vacancies proved to be relevant in the explantation of the kinetic deactivation of nitrogen in co-implanted SiC. This and further evidence for defect aggregates underline the relevance of this notion. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Graphite under the magnetic force microscopePHYSICA STATUS SOLIDI (B) BASIC SOLID STATE PHYSICS, Issue 11 2007T. L. Makarova Abstract In search for magnetically active carbon structures, we have undertaken the magnetic force microscopy study of intrinsic defects at the surface of highly oriented pyrolytic graphite. Most of the observed defects, such as ridges and cleavage edges, are found magnetically inert. However, some of the observed sharp cleavage edges do show magnetic activity , a built-in surface magnetization, which reveals itself as the magnetic force gradient signal sensitive to the polarity of the tip magnetization. These results indicate the existence of a defect related magnetism at room temperature on graphite surface. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] EPR of Nd3+ in congruent and nearly stoichiometric lithium niobatePHYSICA STATUS SOLIDI (B) BASIC SOLID STATE PHYSICS, Issue 2 2006G. Malovichko Abstract Lithium niobate crystals doped with neodymium were studied with the help of electron paramagnetic resonance, EPR in the temperature range of 4.2,20 K. Tremendous narrowing of the EPR lines in nearly stoichiometric samples in comparison with congruent ones allowed us to distinguish four non-equivalent centers, as well as line splitting caused by hyperfine interaction of neodymium electrons with nuclear spins of both magnetic isotopes 143Nd and 145Nd. It is shown that one of the centers has axial C3 symmetry, whereas all others have lowest C1 symmetry due to presence of intrinsic defects or/and charge compensation defects in the near neighborhood of Nd3+. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Deep level transient spectroscopy and TEM analysis of defects in Eu implanted GaNPHYSICA STATUS SOLIDI (C) - CURRENT TOPICS IN SOLID STATE PHYSICS, Issue 7 2005A. Colder Abstract Deep level transient spectroscopy (DLTS) and transmission electron microscopy (TEM) are used to study europium implanted gallium nitride layers. The implantation was realised at room temperature in the random and channeled geometries. From DLTS, we determine intrinsic defects with associated levels located in the band gap (below the conduction band). Besides, we point out a new electron trap named Eu2. Its associated level is located at about Ec ,0.36 eV and the defect is probably related to the europium rare-earth ion. TEM investigation shows a difference in structure caused by changing the geometry of implantation. The random implanted sample contains numerous planar defects. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] High temperature does not alter fatigability in intact mouse skeletal muscle fibresTHE JOURNAL OF PHYSIOLOGY, Issue 19 2009Nicolas Place Intense activation of skeletal muscle results in fatigue development, which involves impaired function of the muscle cells resulting in weaker and slower contractions. Intense muscle activity also results in increased heat production and muscle temperature may rise by up to ,6°C. Hyperthermia is associated with impaired exercise performance in vivo and recent studies have shown contractile dysfunction and premature fatigue development in easily fatigued muscle fibres stimulated at high temperatures and these defects were attributed to oxidative stress. Here we studied whether fatigue-resistant soleus fibres stimulated at increased temperature show premature fatigue development and whether increasing the level of oxidative stress accelerates fatigue development. Intact single fibres or small bundles of soleus fibres were fatigued by 600 ms tetani given at 2 s intervals at 37°C and 43°C, which is the highest temperature the muscle would experience in vivo. Tetanic force in the unfatigued state was not significantly different at the two temperatures. With 100 fatiguing tetani, force decreased by ,15% at both temperatures; the free cytosolic [Ca2+] (assessed with indo-1) showed a similar ,10% decrease at both temperatures. The oxidative stress during fatigue at 43°C was increased by application of 10 ,m hydrogen peroxide or tert-butyl hydroperoxide and this did not cause premature fatigue development. In summary, fatigue-resistant muscle fibres do not display impaired contractility and fatigue resistance at the highest temperature that mammals, including humans, would experience in vivo. Thus, intrinsic defects in fatigue-resistant muscle fibres cannot explain the decreased physical performance at high temperatures. [source] Determinants of Placental VascularityAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2004Donald S. Torry Problem:, Vascular growth during implantation and placentation is critical for successful gestation and it is thought that vascular insufficiencies during placentation contribute to a number of obstetrical complications. However, relatively little is known regarding the regulation of angiogenesis in the placenta. Method of study:, We review literature concerning the potential significance of inadequate placental vascularity as a contributor to the obstetrical complications of spontaneous abortion, fetal growth restriction and preeclampsia. Gene expression assays were used to compare fluctuations of placenta growth factor (PlGF) and PlGF receptor expression in normal and preeclamptic trophoblast in vitro. Results:, Studies have shown that common obstetrical complications manifest altered placental vascularity. Both intrinsic defects (gene knockouts) and extrinsic factors (O2 tension, cytokines, etc) may be responsible for the defects. Some of these factors have been shown to influence trophoblast vascular endothelial growth factor (VEGF)/PlGF expression suggesting this particular family of angiogenic proteins play an important role in placental angiogenesis. Conclusion:, Placental vascularization reflects a complex interaction of regulatory factors. Understanding the regulation of vascular growth in the placenta will provide much needed insight into placenta-related vascular insufficiencies. [source] | |||||||||||||