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Sample records for artery remodeling insulin

  1. Obesity and carotid artery remodeling

    DEFF Research Database (Denmark)

    Kozakova, M; Palombo, C; Morizzo, C;

    2015-01-01

    BACKGROUND/OBJECTIVE: The present study tested the hypothesis that obesity-related changes in carotid intima-media thickness (IMT) might represent not only preclinical atherosclerosis but an adaptive remodeling meant to preserve circumferential wall stress (CWS) in altered hemodynamic conditions...... and CCA LD (266 healthy subjects with wide range of body weight (24-159 kg)); (B) longitudinal associations between CCA LD and 3-year IMT progression rate (ΔIMT; 571 healthy non-obese subjects without increased cardiovascular (CV) risk); (C) the impact of obesity on CCA geometry and CWS (88 obese...... subjects without CV complications and 88 non-obese subjects matched for gender and age). RESULTS: CCA LD was independently associated with SV that was determined by body size. In the longitudinal study, baseline LD was an independent determinant of ΔIMT, and ΔIMT of subjects in the highest LD quartile was...

  2. A gene-centric study of common carotid artery remodelling

    NARCIS (Netherlands)

    Harrison, Seamus C.; Zabaneh, Delilah; Asselbergs, Folkert W.; Drenos, Fotios; Jones, Gregory T.; Shah, Sonia; Gertow, Karl; Sennblad, Bengt; Strawbridge, Rona J.; Gigante, Bruna; Holewijn, Suzanne; De Graaf, Jacqueline; Vermeulen, Sita; Folkersen, Lasse; van Rij, Andre M.; Baldassarre, Damiano; Veglia, Fabrizio; Talmud, Philippa J.; Deanfield, John E.; Agu, Obi; Kivimaki, Mika; Kumari, Meena; Bown, Matthew J.; Nyyssonen, Kristiina; Rauramaa, Rainer; Smit, Andries J.; Franco-Cereceda, Anders; Giral, Philippe; Mannarino, Elmo; Silveira, Angela; Syvanen, Ann-Christine; de Borst, Gert J.; van der Graaf, Yolanda; de Faire, Ulf; Baas, Annette F.; Blankensteijn, Jan D.; Wareham, Nicholas J.; Fowkes, Gerry; Tzoulaki, Ionna; Price, Jacqueline F.; Tremoli, Elena; Hingorani, Aroon D.; Eriksson, Per; Hamsten, Anders; Humphries, Steve E.

    2013-01-01

    Background: Expansive remodelling is the process of compensatory arterial enlargement in response to atherosclerotic stimuli. The genetic determinants of this process are poorly characterized. Methods: Genetic association analyses of inter-adventitial common carotid artery diameter (ICCAD) in the IM

  3. Artery Remodeling Under Axial Twist in Three Days Organ Culture.

    Science.gov (United States)

    Wang, Guo-Liang; Xiao, Yangming; Voorhees, Andrew; Qi, Ying-Xin; Jiang, Zong-Lai; Han, Hai-Chao

    2015-08-01

    Arteries often endure axial twist due to body movement and surgical procedures, but how arteries remodel under axial twist remains unclear. The objective of this study was to investigate early stage arterial wall remodeling under axial twist. Porcine carotid arteries were twisted axially and maintained for three days in ex vivo organ culture systems while the pressure and flow remained the same as untwisted controls. Cell proliferation, internal elastic lamina (IEL) fenestrae shape and size, endothelial cell (EC) morphology and orientation, as well as the expression of matrix metalloproteinases (MMPs), MMP-2 and MMP-9, and tissue inhibitor of metalloproteinase-2 (TIMP-2) were quantified using immunohistochemistry staining and immunoblotting. Our results demonstrated that cell proliferation in both the intima and media were significantly higher in the twisted arteries compared to the controls. The cell proliferation in the intima increased from 1.33 ± 0.21% to 7.63 ± 1.89%, and in the media from 1.93 ± 0.84% to 8.27 ± 2.92% (p culture, a decrease from the initial 15.58 ± 1.29 degrees. These results demonstrate that axial twist can stimulate artery remodeling. These findings complement our understanding of arterial wall remodeling under mechanical stress resulting from pressure and flow variations. PMID:25503524

  4. The redox state of transglutaminase 2 controls arterial remodeling

    DEFF Research Database (Denmark)

    van den Akker, Jeroen; VanBavel, Ed; van Geel, Remon;

    2011-01-01

    While inward remodeling of small arteries in response to low blood flow, hypertension, and chronic vasoconstriction depends on type 2 transglutaminase (TG2), the mechanisms of action have remained unresolved. We studied the regulation of TG2 activity, its (sub) cellular localization, substrates, ...

  5. Molecular Mechanisms of Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension

    Science.gov (United States)

    Leopold, Jane A.; Maron, Bradley A.

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease that is precipitated by hypertrophic pulmonary vascular remodeling of distal arterioles to increase pulmonary artery pressure and pulmonary vascular resistance in the absence of left heart, lung parenchymal, or thromboembolic disease. Despite available medical therapy, pulmonary artery remodeling and its attendant hemodynamic consequences result in right ventricular dysfunction, failure, and early death. To limit morbidity and mortality, attention has focused on identifying the cellular and molecular mechanisms underlying aberrant pulmonary artery remodeling to identify pathways for intervention. While there is a well-recognized heritable genetic component to PAH, there is also evidence of other genetic perturbations, including pulmonary vascular cell DNA damage, activation of the DNA damage response, and variations in microRNA expression. These findings likely contribute, in part, to dysregulation of proliferation and apoptosis signaling pathways akin to what is observed in cancer; changes in cellular metabolism, metabolic flux, and mitochondrial function; and endothelial-to-mesenchymal transition as key signaling pathways that promote pulmonary vascular remodeling. This review will highlight recent advances in the field with an emphasis on the aforementioned molecular mechanisms as contributors to the pulmonary vascular disease pathophenotype. PMID:27213345

  6. Molecular Mechanisms of Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    Jane A. Leopold

    2016-05-01

    Full Text Available Pulmonary arterial hypertension (PAH is a devastating disease that is precipitated by hypertrophic pulmonary vascular remodeling of distal arterioles to increase pulmonary artery pressure and pulmonary vascular resistance in the absence of left heart, lung parenchymal, or thromboembolic disease. Despite available medical therapy, pulmonary artery remodeling and its attendant hemodynamic consequences result in right ventricular dysfunction, failure, and early death. To limit morbidity and mortality, attention has focused on identifying the cellular and molecular mechanisms underlying aberrant pulmonary artery remodeling to identify pathways for intervention. While there is a well-recognized heritable genetic component to PAH, there is also evidence of other genetic perturbations, including pulmonary vascular cell DNA damage, activation of the DNA damage response, and variations in microRNA expression. These findings likely contribute, in part, to dysregulation of proliferation and apoptosis signaling pathways akin to what is observed in cancer; changes in cellular metabolism, metabolic flux, and mitochondrial function; and endothelial-to-mesenchymal transition as key signaling pathways that promote pulmonary vascular remodeling. This review will highlight recent advances in the field with an emphasis on the aforementioned molecular mechanisms as contributors to the pulmonary vascular disease pathophenotype.

  7. Pulmonary arterial remodeling revealed by microfocal x-ray tomography

    Science.gov (United States)

    Karau, Kelly L.; Molthen, Robert C.; Johnson, Roger H.; Dhyani, Anita H.; Haworth, Steven T.; Dawson, Christopher A.

    2001-05-01

    Animal models and micro-CT imaging are useful for understanding the functional consequences of, and identifying the genes involved in, the remodeling of vascular structures that accompanies pulmonary vascular disease. Using a micro-CT scanner to image contrast-enhanced arteries in excised lungs from fawn hooded rats (a strain genetically susceptible to hypoxia induced pulmonary hypertension), we found that portions of the pulmonary arterial tree downstream from a given diameter were morphometrically indistinguishable. This 'self-consistency' property provided a means for summarizing the pulmonary arterial tree architecture and mechanical properties using a parameter vector obtained from measurements of the contiguous set of vessel segments comprising the longest (principal) pathway and its branches over a range of vascular pressures. This parameter vector was used to characterize the pulmonary vascular remodeling that occurred in rats exposed to a hypoxic (11.5% oxygen) environment and provided the input to a hemodynamic model relating structure to function. The major effect of the remodeling was a longitudinally (pulmonary artery to arterioles) uniform decrease in vessel distensibility that resulted in a 90% increase in arterial resistance. Despite the almost uniform change in vessel distensibility, over 50% of the resistance increase was attributable to vessels with unstressed diameters less than 125 microns.

  8. Efficacy of losartan for improving insulin resistance and vascular remodeling in hemodialysis patients.

    Science.gov (United States)

    Sun, Fang; Song, Yan; Liu, Jing; Ma, Li-Jie; Shen, Yang; Huang, Jing; Zhou, Yi-Lun

    2016-01-01

    Insulin resistance and vascular remodeling are prevalent and predict cardiovascular mortality in hemodialysis patients. Angiotensin II (Ang II) may be involved in both pathogenesis. In the present study, we investigated the effects of the Ang II receptor blocker losartan on insulin resistance, arterial stiffness, and carotid artery structure in hemodialysis patients. Seventy-two hemodialysis patients were randomly assigned to receive either losartan 50 mg qd (n = 36) or β-blocker bisoprolol 5 mg qd (n = 36). At the start and at month 12, ambulatory blood pressure (BP) monitoring, aortic pulse wave velocity (PWV) measurements, and carotid artery ultrasound were performed, and homeostasis model assessment index of insulin resistance (HOMA-IR) was determined. During the study period, bioimpedance method was used to evaluate volume status every 3 months. Home-monitored BPs were measured at least monthly. Ambulatory BP decreased significantly and similarly by either losartan or bisoprolol. Decreases in PWVs in losartan group at the end of month 12 were significantly greater than changes in PWV in bisoprolol group (0.9 ± 0.3 vs. 0.4 ± 0.5 m/s, P = 0.021). Common carotid artery intima-media cross-sectional area decreased significantly only in patients treated with losartan (20.3 ± 4.9 vs. 19.1 ± 5.1 mm(2) , P = 0.001), and HOMA-IR was also reduced in losartan group only (1.9 ± 1.0 vs. 1.7 ± 0.8, P = 0.003). Multiple regression analysis showed significant correlations between changes in PWV and changes in HOMA-IR. With comparable BP-lowering efficacy, losartan achieved better improvement in insulin sensitivity, arterial stiffness, and carotid artery hypertrophy in hemodialysis patients. The regression of arterial stiffness may be in part through attenuation in insulin resistance. PMID:26104969

  9. Pulmonary arterial remodeling in chronic obstructive pulmonary disease is lobe dependent.

    Science.gov (United States)

    Wrobel, Jeremy P; McLean, Catriona A; Thompson, Bruce R; Stuart-Andrews, Christopher R; Paul, Eldho; Snell, Gregory I; Williams, Trevor J

    2013-09-01

    Abstract Pulmonary arterial remodeling has been demonstrated in patients with severe chronic obstructive pulmonary disease (COPD), but it is not known whether lobar heterogeneity of remodeling occurs. Furthermore, the relationship between pulmonary hypertension (PH) and pulmonary arterial remodeling in COPD has not been established. Muscular pulmonary arterial remodeling in arteries 0.10-0.25 mm in diameter was assessed in COPD-explanted lungs and autopsy controls. Remodeling was quantified as the percentage wall thickness to vessel diameter (%WT) using digital image analysis. Repeat measures mixed-effects remodeling for %WT was performed according to lobar origin (upper and lower), muscular pulmonary arterial size (small, medium, and large), and echocardiography-based pulmonary arterial pressure (no PH, mild PH, and moderate-to-severe PH). Lobar perfusion and emphysema indices were determined from ventilation-perfusion and computed tomography scans, respectively. Overall, %WT was greater in 42 subjects with COPD than in 5 control subjects ([Formula: see text]). Within the COPD group, %WT was greater in the upper lobes ([Formula: see text]) and in the small muscular pulmonary arteries ([Formula: see text]). Lobar differences were most pronounced in medium and large arteries. Lobar emphysema index was not associated with arterial remodeling. However, there was a significant positive relationship between the lobar perfusion index and pulmonary arterial remodeling ([Formula: see text]). The presence of PH on echocardiography showed only a trend to a small effect on lower lobe remodeling. The pattern of pulmonary arterial remodeling in COPD is complicated and lobe dependent. Differences in regional blood flow partially account for the lobar heterogeneity of pulmonary arterial remodeling in COPD. PMID:24618551

  10. A gene-centric study of common carotid artery remodelling

    Science.gov (United States)

    Harrison, Seamus C.; Zabaneh, Delilah; Asselbergs, Folkert W.; Drenos, Fotios; Jones, Gregory T.; Shah, Sonia; Gertow, Karl; Sennblad, Bengt; Strawbridge, Rona J.; Gigante, Bruna; Holewijn, Suzanne; De Graaf, Jacqueline; Vermeulen, Sita; Folkersen, Lasse; van Rij, Andre M.; Baldassarre, Damiano; Veglia, Fabrizio; Talmud, Philippa J.; Deanfield, John E.; Agu, Obi; Kivimaki, Mika; Kumari, Meena; Bown, Matthew J.; Nyyssönen, Kristiina; Rauramaa, Rainer; Smit, Andries J.; Franco-Cereceda, Anders; Giral, Philippe; Mannarino, Elmo; Silveira, Angela; Syvänen, Ann-Christine; de Borst, Gert J.; van der Graaf, Yolanda; de Faire, Ulf; Baas, Annette F.; Blankensteijn, Jan D.; Wareham, Nicholas J.; Fowkes, Gerry; Tzoulaki, Ionna; Price, Jacqueline F.; Tremoli, Elena; Hingorani, Aroon D.; Eriksson, Per; Hamsten, Anders; Humphries, Steve E.

    2013-01-01

    Background Expansive remodelling is the process of compensatory arterial enlargement in response to atherosclerotic stimuli. The genetic determinants of this process are poorly characterized. Methods Genetic association analyses of inter-adventitial common carotid artery diameter (ICCAD) in the IMPROVE study (n = 3427) using the Illumina 200k Metabochip was performed. Single nucleotide polymorphisms (SNPs) that met array-wide significance were taken forward for analysis in three further studies (n = 5704), and tested for association with Abdominal Aortic Aneurysm (AAA). Results rs3768445 on Chromosome 1q24.3, in a cluster of protein coding genes (DNM3, PIGC, C1orf105) was associated with larger ICCAD in the IMPROVE study. For each copy of the rare allele carried, ICCAD was on average 0.13 mm greater (95% CI 0.08–0.18 mm, P = 8.2 × 10−8). A proxy SNP (rs4916251, R2 = 0.99) did not, however, show association with ICCAD in three follow-up studies (P for replication = 0.29). There was evidence of interaction between carotid intima-media thickness (CIMT) and rs4916251 on ICCAD in two of the cohorts studies suggesting that it plays a role in the remodelling response to atherosclerosis. In meta-analysis of 5 case–control studies pooling data from 5007 cases and 43,630 controls, rs4916251 was associated with presence of AAA 1.10, 95% CI 1.03–1.17, p = 2.8 × 10−3, I2 = 18.8, Q = 0.30). A proxy SNP, rs4916251 was also associated with increased expression of PIGC in aortic tissue, suggesting that this may the mechanism by which this locus affects vascular remodelling. Conclusions Common variation at 1q24.3 is associated with expansive vascular remodelling and risk of AAA. These findings support a hypothesis that pathways involved in systemic vascular remodelling play a role in AAA development. PMID:23246012

  11. Tissue remodeling of rat pulmonary arteries in recovery from hypoxic hypertension

    OpenAIRE

    Li, Zhuangjie; Huang, Wei; Jiang, Zong Lai; Gregersen, Hans; Fung, Yuan-Cheng

    2004-01-01

    The reversibility of tissue remodeling is of general interest to medicine. Pulmonary arterial tissue remodeling during hypertension induced by hypoxic breathing is well known, but little has been said about the recovery of the arterial wall when the blood pressure is lowered again. We hypothesize that tissue recovery is a function of the oxygen concentration, blood pressure, location on the vascular tree, and time. We measured the changes of blood pressure, vessel lumen, vessel wall thickness...

  12. Buckling Reduces eNOS Production and Stimulates Extracellular Matrix Remodeling in Arteries in Organ Culture.

    Science.gov (United States)

    Xiao, Yangming; Liu, Qin; Han, Hai-Chao

    2016-09-01

    Artery buckling alters the fluid shear stress and wall stress in the artery but its temporal effect on vascular wall remodeling is poorly understood. The purpose of this study was to investigate the early effect of artery buckling on endothelial nitric oxide synthase (eNOS) expression and extracellular matrix remodeling. Bilateral porcine carotid arteries were maintained in an ex vivo organ culture system with and without buckling while under the same physiological pressure and flow rate for 3-7 days. Matrix metalloproteinase-2 (MMP-2), MMP-9, fibronectin, elastin, collagen I, III and IV, tissue inhibitor of metalloproteinase-2 (TIMP-2), and eNOS were determined using Western blotting and immunohistochemistry. Our results showed that MMP-2 expression level was significantly higher in buckled arteries than in the controls and higher at the inner curve than at the outer curve of buckled arteries, while collagen IV content showed an opposite trend, suggesting that artery buckling increased MMP-2 expression and collagen IV degradation in a site-specific fashion. However, no differences for MMP-9, fibronectin, elastin, collagen I, III, and TIMP-2 were observed among the outer and inner curve sides of buckled arteries and straight controls. Additionally, eNOS expression was significantly decreased in buckled arteries. These results suggest that artery buckling triggers uneven wall remodeling that could lead to development of tortuous arteries. PMID:26913855

  13. Vascular-Leukocyte Interactions : Mechanisms of Human Decidual Spiral Artery Remodeling in Vitro

    OpenAIRE

    Hazan, Aleah D.; Smith, Samantha D.; Jones, Rebecca L; Whittle, Wendy; Lye, Stephen J.; Dunk, Caroline E.

    2010-01-01

    Transformation of uterine spiral arteries is critical for healthy human pregnancy. We recently proposed a role for maternal leukocytes in decidual spiral artery remodeling and suggested that matrix metalloprotease (MMP) activity contributed to the destruction of the arterial wall. In the current study we used our first trimester placental-decidual co-culture (PDC) model to define the temporal relationship and test the mechanistic aspects of this process. PDC experiments were assessed by image...

  14. Changes in pulmonary arterial wall mechanical properties and lumenal architecture with induced vascular remodeling

    Science.gov (United States)

    Molthen, Robert C.; Heinrich, Amy E.; Haworth, Steven T.; Dawson, Christopher A.

    2004-04-01

    To explore and quantify pulmonary arterial remodeling we used various methods including micro-CT, high-resolution 3-dimensional x-ray imaging, to examine the structure and function of intact pulmonary vessels in isolated rat lungs. The rat is commonly used as an animal model for studies of pulmonary hypertension (PH) and the accompanying vascular remodeling, where vascular remodeling has been defined primarily by changes in the vessel wall composition in response to hypertension inducing stimuli such as chronic hypoxic exposure (CHE) or monocrotaline (MCT) injection. Little information has been provided as to how such changes affect the vessel wall mechanical properties or the lumenal architecture of the pulmonary arterial system that actually account for the hemodynamic consequences of the remodeling. In addition, although the link between primary forms of pulmonary hypertension and inherited genetics is well established, the role that genetic coding plays in hemodynamics and vascular remodeling is not. Therefore, we are utilizing Fawn-Hooded (FH), Sprague-Dawley (SD) and Brown Norway (BN)rat strains along with unique imaging methods to parameterize both vessel distensibility and lumenal morphometry using a principal pulmonary arterial pathway analysis based on self-consistency. We have found for the hypoxia model, in addition to decreased body weight, increased hematocrit, increased right ventricular hypertrophy, the distensibility of the pulmonary arteries is shown to decrease significantly in the presence of remodeling.

  15. Molecular analysis of arterial remodeling: a novel application of infrared imaging

    Science.gov (United States)

    Herman, Brad C.; Kundi, Rishi; Yamanouchi, Dai; Kent, K. Craig; Liu, Bo; Pleshko, Nancy

    2009-02-01

    Arterial remodeling, i.e. changes in size and/or structure of arteries, plays an important role in vascular disease. Conflicting findings have been reported as to whether an abundance of collagen causes inward or outward remodeling, phenomena that result in either a smaller or larger lumen, respectively. We hypothesize that the amount, type and quality of collagen influence the remodeling response. Here, we create mechanical injury to the rat carotid artery using a balloon catheter, and this leads to inward remodeling. Treatment of the artery with Connective Tissue Growth Factor (CTGF) causes outward remodeling. We investigated the arterial composition in injured CTGF-treated and non-CTGF-treated and sham CTGF-treated and non-CTGF treated arteries 14 days post-injury (n = 7-8 per group) using infrared imaging. A Perkin Elmer Spotlight Spectrum 300 FT-IR microscope was used for data collection. Cross-sections of paraffinembedded arteries were scanned at 2 cm-1 spectral resolution with spatial resolution of 6.25 μm/pixel, and data analyzed using Malvern Instruments ISys 5.0. Post-injury, we found a nearly 50% reduction in the average 1338/AM2 area ratio (correlated to collagen helical integrity). The most dramatic change was a 600% increase in the 1660/1690 peak height ratio, which has previously been related to collagen crosslink maturity. In all cases, CTGF treatment resulted in the observed changes in peak parameters normalized back to control values. Overall, these preliminary studies demonstrate that infrared imaging can provide insight into the underlying molecular changes that contribute to arterial disease.

  16. The impact of exercise training on conduit artery wall thickness and remodeling in chronic heart failure patients

    NARCIS (Netherlands)

    Maiorana, A.J.; Naylor, L.H.; Exterkate, A.; Swart, A.; Thijssen, D.H.J.; Lam, K.; O'Driscoll, G.; Green, D.J.

    2011-01-01

    Exercise training is an important adjunct to medical therapy in chronic heart failure, but the extent to which exercise impacts on conduit artery remodeling is unknown. The aim of this study was to evaluate the impact of aerobic and resistance exercise training modalities on arterial remodeling in p

  17. β Integrins Mediate FAK Y397 Autophosphorylation of Resistance Arteries during Eutrophic Inward Remodeling in Hypertension

    OpenAIRE

    Heerkens, Egidius H.J; Quinn, Lisa; Withers, Sarah B.; Heagerty, Anthony M

    2014-01-01

    Human essential hypertension is characterized by eutrophic inward remodeling of the resistance arteries with little evidence of hypertrophy. Upregulation of αVβ3 integrin is crucial during this process. In order to investigate the role of focal adhesion kinase (FAK) activation in this process, the level of FAK Y397 autophosphorylation was studied in small blood vessels from young TGR(mRen2)27 animals as blood pressure rose and eutrophic inward remodeling took place. Between weeks 4 and 5, thi...

  18. Remodeling lipid metabolism and improving insulin responsiveness in human primary myotubes.

    Directory of Open Access Journals (Sweden)

    Lauren M Sparks

    Full Text Available OBJECTIVE: Disturbances in lipid metabolism are strongly associated with insulin resistance and type 2 diabetes (T2D. We hypothesized that activation of cAMP/PKA and calcium signaling pathways in cultured human myotubes would provide further insight into regulation of lipid storage, lipolysis, lipid oxidation and insulin responsiveness. METHODS: Human myoblasts were isolated from vastus lateralis, purified, cultured and differentiated into myotubes. All cells were incubated with palmitate during differentiation. Treatment cells were pulsed 1 hour each day with forskolin and ionomycin (PFI during the final 3 days of differentiation to activate the cAMP/PKA and calcium signaling pathways. Control cells were not pulsed (control. Mitochondrial content, (14C lipid oxidation and storage were measured, as well as lipolysis and insulin-stimulated glycogen storage. Myotubes were stained for lipids and gene expression measured. RESULTS: PFI increased oxidation of oleate and palmitate to CO(2 (p<0.001, isoproterenol-stimulated lipolysis (p = 0.01, triacylglycerol (TAG storage (p<0.05 and mitochondrial DNA copy number (p = 0.01 and related enzyme activities. Candidate gene and microarray analysis revealed increased expression of genes involved in lipolysis, TAG synthesis and mitochondrial biogenesis. PFI increased the organization of lipid droplets along the myofibrillar apparatus. These changes in lipid metabolism were associated with an increase in insulin-mediated glycogen storage (p<0.001. CONCLUSIONS: Activation of cAMP/PKA and calcium signaling pathways in myotubes induces a remodeling of lipid droplets and functional changes in lipid metabolism. These results provide a novel pharmacological approach to promote lipid metabolism and improve insulin responsiveness in myotubes, which may be of therapeutic importance for obesity and type 2 diabetes.

  19. Calcium antagonist verapamil prevented pulmonary arterial hypertension in broilers with ascites by arresting pulmonary vascular remodeling.

    Science.gov (United States)

    Yang, Ying; Qiao, Jian; Wang, Huiyu; Gao, Mingyu; Ou, Deyuan; Zhang, Jianjun; Sun, Maohong; Yang, Xin; Zhang, Xiaobo; Guo, Yuming

    2007-04-30

    Calcium signaling has been reported to be involved in the pathogenesis of hypertension. Verapamil, one of the calcium antagonists, is used to characterize the role of calcium signaling in the development of pulmonary arterial hypertension syndrome in broilers. The suppression effect of verapamil on pulmonary arterial hypertension and pulmonary vascular remodeling was examined in broilers, from the age of 16 days to 43 days. Our results showed that oral administration of lower dose of verapamil (5 mg/kg body weight every 12 h) prevented the mean pulmonary arterial pressure, the ascites heart index and the erythrocyte packed cell volume of birds at low temperature from increasing, the heart rate from decreasing, and pulmonary arteriole median from thickening, and no pulmonary arteriole remodeling in broilers treated with the two doses of verapamil at low temperature was observed. Our results indicated that calcium signaling was involved in the development of broilers' pulmonary arterial hypertension, which leads to the development of ascites, and we suggest that verapamil may be used as a preventive agent to reduce the occurrence and development of pulmonary arterial hypertension in broilers. PMID:17320074

  20. 20-HETE induces remodeling of renal resistance arteries independent of blood pressure elevation in hypertension.

    Science.gov (United States)

    Ding, Yan; Wu, Cheng-Chia; Garcia, Victor; Dimitrova, Irina; Weidenhammer, Adam; Joseph, Gregory; Zhang, Frank; Manthati, Vijay L; Falck, John R; Capdevila, Jorge H; Schwartzman, Michal L

    2013-09-01

    20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P-450 (Cyp)-derived arachidonic acid metabolite that has been shown to increase smooth muscle contractions and proliferation, stimulate endothelial dysfunction and activation, and promote hypertension. We examined if 20-HETE contributes to microvascular remodeling in hypertension. In Sprague-Dawley rats, administration of the 20-HETE biosynthesis inhibitor HET0016 or the 20-HETE antagonist N-20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE) prevented 5α-dihydrotestosterone (DHT)-induced increases in blood pressure as well as abrogated DHT-induced increases in the media-to-lumen ratio (M/L), media thickness, and collagen IV deposition in renal interlobar arteries. Reserpine prevented blood pressure elevation in DHT-treated rats but did not affect microvascular remodeling (M/L, media thickness, and collagen deposition); under these conditions, treatment with the 20-HETE antagonist attenuated microvascular remodeling, suggesting that 20-HETE contributes to DHT-induced vascular remodeling independent of blood pressure elevation. In Cyp4a14(-/-) mice, which display androgen-driven and 20-HETE-dependent hypertension, treatment with the 20-HETE antagonist abolished remodeling of renal resistance arteries measured as media thickness (24 ± 1 vs. 15 ± 1 μm) and M/L (0.29 ± 0.03 vs. 0.17 ± 0.01). Moreover, in Cyp4a12 transgenic mice in which the expression of Cyp4a12-20-HETE synthase is driven by a tetracycline-sensitive promoter, treatment with doxycycline resulted in blood pressure elevation (140 ± 4 vs. 92 ± 5 mmHg) and a significant increase in remodeling of renal resistance arteries (media thickness: 23 ± 1 vs. 16 ± 1 μm; M/L: 0.39 ± 0.04 vs. 0.23 ± 0.02); these increases were abrogated by cotreatment with 20-HEDE. This study demonstrated that 20-HETE is a key regulator of microvascular remodeling in hypertension; its effect is independent of blood pressure elevation and androgen levels. PMID

  1. Evaluation of coronary artery remodeling in patients with acute coronary syndrome and stable angina by multislice computed tomography

    International Nuclear Information System (INIS)

    Multislice computed tomography (MSCT) was used to evaluate coronary artery remodeling in patients with acute coronary syndrome (ACS) and stable angina (SA). MSCT was performed in 31 patients with ACS and 26 patients with SA and intravascular ultrasound (IVUS) was performed in 28 of these 57 patients. In both the MSCT and IVUS analyses, coronary artery remodeling was assessed by the remodeling index (RI): RI>1.10 was defined as positive coronary artery remodeling (PCAR) and RI<0.95 was defined as negative coronary artery remodeling (NCAR). The RI assessed by MSCT closely correlated with that of IVUS (r=0.86, n=28). The vessel area at the region of maximum luminal narrowing was also comparable between the MSCT and IVUS measurements (r=0.92). PCAR was present in 19 patients (61.3%) with ACS, but in none of the patients with SA (p<0.0001). However, NCAR was present in only 1 patient with ACS (3.2%), but was present in 18 patients (62.9%) with SA. The RI was significantly larger in patients with ACS (1.19±0.18) than in those with SA (0.89±0.10, p<0.0001). MSCT accurately assesses coronary artery remodeling. (author)

  2. Obese children and adolescents have elevated nighttime blood pressure independent of insulin resistance and arterial stiffness

    DEFF Research Database (Denmark)

    Hvidt, Kristian N; Olsen, Michael H; Holm, Jens-Christian;

    2014-01-01

    BACKGROUND: Insulin resistance has been related to elevated blood pressure (BP) in obese children and may adversely affect the vasculature by arterial stiffening. The objective was to investigate whether daytime and nighttime BP were elevated and related to insulin resistance and arterial stiffness...... in obese children and adolescents. METHODS: Ninety-two obese patients aged 10-18 years were compared with 49 healthy control individuals. Insulin resistance was measured as the homeostatic assessment model (HOMA), and arterial stiffness was measured as carotid-femoral pulse wave velocity (cfPWV). RESULTS...... analyses, the higher nighttime BP in the obese group was independent of logHOMA and cfPWV. CONCLUSIONS: Obese children had a higher nighttime BP when compared with the control group independently of insulin resistance and arterial stiffness. No relationship was found between insulin resistance and arterial...

  3. Time course of arterial remodelling in diameter and wall thickness above and below the lesion after a spinal cord injury

    OpenAIRE

    Dick H J Thijssen; de Groot, Patricia C. E.; van den Bogerd, Arne; Veltmeijer, Matthijs; Cable, N. Timothy; Green, Daniel J.; Hopman, Maria T. E.

    2012-01-01

    Physical inactivity in response to a spinal cord injury (SCI) represents a potent stimulus for conduit artery remodelling. Changes in conduit artery characteristics may be induced by the local effects of denervation (and consequent extreme inactivity below the level of the lesion), and also by systemic adaptations due to whole body inactivity. Therefore, we assessed the time course of carotid (i.e. above lesion) and common femoral artery (i.e. below lesion) lumen diameter and wall thickness a...

  4. Impaired flow-induced arterial remodeling in DOCA-salt hypertensive rats

    DEFF Research Database (Denmark)

    Lemkens, Pieter; Nelissen, Jelly; Meens, Merlijn J P M T;

    2012-01-01

    )-salt hypertension in rats, a model for an upregulated endothelin-1 system. Mesenteric small arteries (MrA) were exposed to low blood flow (LF) or high blood flow (HF) for 4 or 7 weeks. The bioavailability of vasoactive peptides was modified by chronic treatment of the rats with the dual neutral endopeptidase (NEP......)/endothelin-converting enzyme (ECE) inhibitor SOL1. After 3 or 6 weeks of hypertension, the MrA showed hypertrophic arterial remodeling (3 weeks: media cross-sectional area (mCSA): 10±1 × 10(3) to 17±2 × 10(3) μm(2); 6 weeks: 13±2 × 10(3) to 24±3 × 10(3) μm(2)). After 3, but not 6, weeks of hypertension, the arterial diameter...... was increased (Ø: 385±13 to 463±14 μm). SOL1 reduced hypertrophy after 3 weeks of hypertension (mCSA: 6 × 10(3)±1 × 10(3) μm(2)). The diameter of the HF arteries of normotensive rats increased (Ø: 463±22 μm) but no expansion occurred in the HF arteries of hypertensive rats (Ø: 471±16 μm). MrA from SOL...

  5. Effect of L-Arginine on Pulmonary Artery Smooth Muscle Cell Apoptosis in Rats with Hypoxic Pulmonary Vascular Structural Remodeling

    Institute of Scientific and Technical Information of China (English)

    Ingrid Karmane SUMOU; Jun-Bao DU; Bing WEI; Chun-Yu ZHANG; Jian-Guang QI; Chao-Shu TANG

    2006-01-01

    This study investigated the effect of L-arginine (L-Arg) on the apoptosis of pulmonary artery smooth muscle cells (PASMC) in rats with hypoxic pulmonary vascular structural remodeling, and its mechanisms. Seventeen Wistar rats were randomly divided into a control group (n=5), a hypoxia group (n=7), and a hypoxia+L-Arg group (n=5). The morphologic changes of lung tissues were observed under optical microscope. Using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphatebiotin nick end labeling assay, the apoptosis of PASMC was examined. Fas expression in PASMC was examined using immunohistochemistry. The results showed that the percentage of muscularized artery in small pulmonary vessels, and the relative medial thickness and relative medial area of the small and median pulmonary muscularized arteries in the hypoxic group were all significantly increased. Pulmonary vascular structural remodeling developed after hypoxia. Apoptotic smooth muscle cells of the small and median pulmonary arteries in the hypoxia group were significantly less than those in the control group. After 14 d of hypoxia, Fas expression by smooth muscle cells of median and small pulmonary arteries was significantly inhibited. L-Arg significantly inhibited hypoxic pulmonary vascular structural remodeling in association with an augmentation of apoptosis of smooth muscle cells as well as Fas expression in PASMC. These results showed that L-Arg could play an important role in attenuating hypoxic pulmonary vascular structural remodeling by upregulating Fas expression in PASMC, thus promoting the apoptosis of PASMC.

  6. Specialized proresolving lipid mediators in patients with coronary artery disease and their potential for clot remodeling.

    Science.gov (United States)

    Elajami, Tarec K; Colas, Romain A; Dalli, Jesmond; Chiang, Nan; Serhan, Charles N; Welty, Francine K

    2016-08-01

    Inflammation in arterial walls leads to coronary artery disease (CAD). Because specialized proresolving lipid mediators (SPMs; lipoxins, resolvins, and protectins) stimulate resolution of inflammation in animal models, we tested whether n-3 fatty acids impact SPM profiles in patients with CAD and promote clot remodeling. Six patients with stable CAD were randomly assigned to either treatment with daily 3.36 g Lovaza for 1 yr or without. Targeted lipid mediator-metabololipidomics showed that both groups had absence of resolvin D1 (RvD1), RvD2, RvD3, RvD5 and resolvin E1-all of which are present in healthy patients. Those not taking Lovaza had an absence of aspirin-triggered resolvin D3 (AT-RvD3) and aspirin-triggered lipoxin B4 (AT-LXB4). Lovaza treatment restored AT-RvD3 and AT-LXB4 and gave levels of RvD6 and aspirin-triggered protectin D1 (AT-PD1) twice as high (resolvin E2 ∼5 fold) as well as lower prostaglandins. Principal component analysis indicated positive relationships for patients with CAD who were receiving Lovaza with increased AT-RvD3, RvD6, AT-PD1, and AT-LXB4 SPMs identified in Lovaza-treated patients with CAD enhanced ∼50% at 1 nM macrophage uptake of blood clots. These results indicate that patients with CAD have lower levels and/or absence of specific SPMs that were restored with Lovaza; these SPMs promote macrophage phagocytosis of blood clots. Together, they suggest that low vascular SPMs may enable progression of chronic vascular inflammation predisposing to coronary atherosclerosis and to thrombosis.-Elajami, T. K., Colas, R. A., Dalli, J., Chiang, N., Serhan, C. N., Welty, F. K. Specialized proresolving lipid mediators in patients with coronary artery disease and their potential for clot remodeling. PMID:27121596

  7. Rosiglitazone reverses endothelial dysfunction but not remodeling of femoral artery in Zucker diabetic fatty rats

    Directory of Open Access Journals (Sweden)

    Onyia Jude E

    2010-05-01

    Full Text Available Abstract Objectives Endothelial dysfunction precedes atherogenesis and clinical complications in type 2 diabetes. The vascular dysfunction in Zucker diabetic fatty (ZDF rats was evaluated at different ages along with the effect of treatment with rosiglitazone (Rosi on endothelial function and mechanical remodeling. Methods The Rosi treatment was given to ZDF rats for 3 weeks. The endothelium-dependent vasodilation and α-adrenoceptor-dependent vasoconstriction of femoral arteries were studied using an ex-vivo isovolumic myograph. The biomechanical passive property of the arteries was studied in Ca2+-free condition. The expressions of endothelial nitric oxide synthase (eNOS, α-adrenoceptor, matrix metalloproteinase 9 (MMP9, and elastase were evaluated. Results Endothelium-dependent vasorelaxation of the femoral artery was blunted at low doses in ZDF rats at 11 weeks of age and attenuated at all doses in ZDF rats at 19 weeks of age. The expression of eNOS was consistent with the endothelium-dependent vasorelaxation. The α-adrenoceptor was activated and the mechanical elastic modulus was increased in ZDF rats at 19 weeks of age. The expressions of α-adrenoceptor, MMP9, and elastase were up regulated in ZDF rats at 19 weeks of age. Rosi treatment for 3 weeks restored endothelium-dependent vasorelaxation and the expression of eNOS and the adrenoceptor activation at the doses below 10-6 mole/L in ZDF rats at 19 weeks of age. Rosi treatment for 3 weeks did not, however, improve the mechanical properties of blood vessel, the expressions of α-adrenoceptor, MMP9, and elastase in ZDF rats. Conclusion The endothelial dysfunction and mechanical remodeling are observed as early as 19 weeks of age in ZDF rat. Rosi treatment for 3 weeks improves endothelial function but not mechanical properties.

  8. Double-balloon remodeling for coil embolization of a primitive trigeminal artery variant aneurysm. A case report.

    Science.gov (United States)

    Takigawa, Tomoji; Suzuki, Kensuke; Sugiura, Yoshiki; Suzuki, Ryotaro; Takano, Issei; Shimizu, Nobuyuki; Tanaka, Yoshihiro; Hyodo, Akio

    2014-01-01

    Here we describe the case of a patient with a wide-necked unruptured aneurysm arising at origin of a persistent primitive trigeminal artery (PTA) variant from the right internal carotid artery (ICA), supplying the territory of the right superior cerebellar artery and the anterior inferior cerebellar artery. To preserve the ICA and the PTA variant, coil embolization of the aneurysm was performed using a double-balloon remodeling technique (HyperForm™ and HyperGlide™ Occlusion Balloon Systems; ev3 Endovascular Inc., Irvine, CA, USA). The association of a PTA variant with an aneurysm is very rare. To our knowledge, this is the first description of the use of coil embolization using double-balloon remodeling to treat a PTA variant aneurysm. This technique permits complete embolization and reduces the risk of cerebral and cerebellar ischemia. PMID:24976091

  9. Treatment with continuous subcutaneous insulin infusion is associated with lower arterial stiffness

    DEFF Research Database (Denmark)

    Vestergaard Rosenlund, Signe; Theilade, Simone; Hansen, Tine Willum;

    2014-01-01

    AIMS: To investigate the relationship between arterial stiffness and insulin treatment mode [continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI)] in type 1 diabetes patients. METHODS: Cross-sectional study, from 2009 to 2011, including 601 Caucasian type 1...

  10. Remodeling of the pulmonary artery induced by metastatic gastric carcinoma: a histopathological analysis of 51 autopsy cases

    International Nuclear Information System (INIS)

    Gastric carcinoma remains the second commonest cause of cancer deaths worldwide. Presence of the carcinoma cell in the pulmonary artery is serious condition that might cause remodeling of the pulmonary artery. The present study conducted detailed histopathological analyses to elucidate how gastric carcinoma cells may affect the structure and hemodynamics of pulmonary arteries. Remodeling of the pulmonary artery was assessed based on measurements of arterial diameters and stenosis rates from the autopsies, and their correlation were also validated. We additionally calculated 95 percent confidential intervals (CIs) for the rate of stenosis in groups of pulmonary arteries of different caliber zones (under 100, 100 to 300, and over 300 micrometer). The right ventricular thickness was measured and examined whether it correlated with the rate of pulmonary arterial stenosis. A total of 4612 autopsy cases were recorded at our institute, among which 168 had gastric carcinoma. Finally, 51 cases of the gastric carcinoma were employed for the study which had carcinoma cells in the lumen of the pulmonary artery. The mean right ventricular wall thickness of these cases was 3.14 mm. There were significant positive associations between the rates of pulmonary arterial stenosis and right ventricular thickness from pulmonary arteries of diameter under 100, 100 to 300, and over 300 micrometer. In these zones, 31, 31, and 33 cases had rates of pulmonary arterial stenosis that were below the lower limit of the 95 percent CI values, respectively. On the other hand, among cases with significant pulmonary stenosis, 17 of 18 cases with stenosis in the over 300 micrometer zone involved pulmonary arteries of both in the under 100 and 100 to 300 micrometer zones. One-third of autopsy with advanced gastric carcinoma had carcinoma cells in lumen of pulmonary artery, but implantation and proliferation may be essential to induce intimal thickening that causes an increasing of pulmonary arterial

  11. Nicorandil prevents right ventricular remodeling by inhibiting apoptosis and lowering pressure overload in rats with pulmonary arterial hypertension.

    Directory of Open Access Journals (Sweden)

    Xiang-Rong Zuo

    Full Text Available BACKGROUND: Most of the deaths among patients with severe pulmonary arterial hypertension (PAH are caused by progressive right ventricular (RV pathological remodeling, dysfunction, and failure. Nicorandil can inhibit the development of PAH by reducing pulmonary artery pressure and RV hypertrophy. However, whether nicorandil can inhibit apoptosis in RV cardiomyocytes and prevent RV remodeling has been unclear. METHODOLOGY/PRINCIPAL FINDINGS: RV remodeling was induced in rats by intraperitoneal injection of monocrotaline (MCT. RV systolic pressure (RVSP was measured at the end of each week after MCT injection. Blood samples were drawn for brain natriuretic peptide (BNP ELISA analysis. The hearts were excised for histopathological, ultrastructural, immunohistochemical, and Western blotting analyses. The MCT-injected rats exhibited greater mortality and less weight gain and showed significantly increased RVSP and RV hypertrophy during the second week. These worsened during the third week. MCT injection for three weeks caused pathological RV remodeling, characterized by hypertrophy, fibrosis, dysfunction, and RV mitochondrial impairment, as indicated by increased levels of apoptosis. Nicorandil improved survival, weight gain, and RV function, ameliorated RV pressure overload, and prevented maladaptive RV remodeling in PAH rats. Nicorandil also reduced the number of apoptotic cardiomyocytes, with a concomitant increase in Bcl-2/Bax ratio. 5-hydroxydecanoate (5-HD reversed these beneficial effects of nicorandil in MCT-injected rats. CONCLUSIONS/SIGNIFICANCE: Nicorandil inhibits PAH-induced RV remodeling in rats not only by reducing RV pressure overload but also by inhibiting apoptosis in cardiomyocytes through the activation of mitochondrial ATP-sensitive K(+ (mitoK(ATP channels. The use of a mitoK(ATP channel opener such as nicorandil for PAH-associated RV remodeling and dysfunction may represent a new therapeutic strategy for the amelioration of RV

  12. Appropriate density of PCL nano-fiber sheath promoted muscular remodeling of PGS/PCL grafts in arterial circulation.

    Science.gov (United States)

    Yang, Xin; Wei, Jianhua; Lei, Delin; Liu, Yanpu; Wu, Wei

    2016-05-01

    Cell-free approach represents a philosophical shift from the prevailing focus on cells in vascular tissue engineering. Porous elastomeric grafts made of poly(glycerol sebacate) (PGS) enforced with polycaprolactone (PCL) nano-fibers degrade rapidly and yield neoarteries nearly free of foreign materials in rat abdominal aorta. However, considering the larger variation of blood pressure and slower host remodeling in human body than in rat, it is important to investigate the in vivo performance of PGS-PCL graft with enhanced mechanical properties, so that optimized arterial grafts could be developed for clinical translation. We acquired increasingly compacted sheath by prolonging the electrospinning period of PCL appropriately, which significantly enforced whole grafts. The rational design of sheath density significantly decreased the risk of dilation, rupture as well as enabling the long-term muscular remodeling. Since 3-12 months after implantation, the PGS grafts with rationally strengthened sheath were remodeled into neoarteries resembled native arteries in the following aspects: high patency rate and even vessel wall thickness; a confluent endothelium and contractile smooth muscle layers; expression of elastin, collagen and glycosaminoglycan; tough and compliant mechanical properties. Although loose sheath may result in rupture of vessel wall, adequate porosity was proved to be essential for sheath structure and directly determined muscular remodeling through M2 macrophage involved constructive remodeling. Therefore, this study confirmed that adequate density of PCL sheath in PGS grafts could initiate stable and high-quality muscular remodeling, which contributes to long-term success in arterial circulation before clinical translation. PMID:26943048

  13. Leukemia Inhibitory Factor (LIF) Inhibition during Mid-Gestation Impairs Trophoblast Invasion and Spiral Artery Remodelling during Pregnancy in Mice.

    Science.gov (United States)

    Winship, Amy; Correia, Jeanne; Zhang, Jian-Guo; Nicola, Nicos A; Dimitriadis, Evdokia

    2015-01-01

    The placenta forms the interface between the maternal and fetal circulation and is critical for the establishment of a healthy pregnancy. Trophoblast cell proliferation, migration and invasion into the endometrium are fundamental events in the initiation of placentation. Leukemia inhibitory factor (LIF) has been shown to promote trophoblast invasion in vitro, however its precise role in trophoblast invasion in vivo is unknown. We hypothesized that LIF would be required for normal trophoblast invasion and spiral artery remodeling in mice. Both LIF and its receptor (LIFRα) co-localized with cytokeratin-positive invasive endovascular extravillous trophoblasts (EVT) in mouse implantation sites during mid-gestation. Temporally blocking LIF action during specific periods of placental development via administration of our unique LIFRα antagonist, PEGLA, resulted in abnormal trophoblast invasion and impaired spiral artery remodeling compared to PEG control. PEGLA-treated mouse decidual vessels were characterized by retention of α-smooth muscle actin (αSMA)-positive vascular smooth muscle cells (VSMCs), while PEG control decidual vessels were remodelled by cytokeratin-positive trophoblasts. LIF blockade did not alter F4/80-positive decidual macrophage numbers between treatment groups, but resulted in down-regulation of decidual transcript levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-10 (IL-10), which are important immune cell activation factors that promote spiral artery remodeling during pregnancy. Our data suggest that LIF plays an important role in trophoblast invasion in vivo and may facilitate trophoblast-decidual-immune cell cross talk to enable adequate spiral artery remodeling. PMID:26479247

  14. Leukemia Inhibitory Factor (LIF Inhibition during Mid-Gestation Impairs Trophoblast Invasion and Spiral Artery Remodelling during Pregnancy in Mice.

    Directory of Open Access Journals (Sweden)

    Amy Winship

    Full Text Available The placenta forms the interface between the maternal and fetal circulation and is critical for the establishment of a healthy pregnancy. Trophoblast cell proliferation, migration and invasion into the endometrium are fundamental events in the initiation of placentation. Leukemia inhibitory factor (LIF has been shown to promote trophoblast invasion in vitro, however its precise role in trophoblast invasion in vivo is unknown. We hypothesized that LIF would be required for normal trophoblast invasion and spiral artery remodeling in mice. Both LIF and its receptor (LIFRα co-localized with cytokeratin-positive invasive endovascular extravillous trophoblasts (EVT in mouse implantation sites during mid-gestation. Temporally blocking LIF action during specific periods of placental development via administration of our unique LIFRα antagonist, PEGLA, resulted in abnormal trophoblast invasion and impaired spiral artery remodeling compared to PEG control. PEGLA-treated mouse decidual vessels were characterized by retention of α-smooth muscle actin (αSMA-positive vascular smooth muscle cells (VSMCs, while PEG control decidual vessels were remodelled by cytokeratin-positive trophoblasts. LIF blockade did not alter F4/80-positive decidual macrophage numbers between treatment groups, but resulted in down-regulation of decidual transcript levels of monocyte chemoattractant protein-1 (MCP-1 and interleukin-10 (IL-10, which are important immune cell activation factors that promote spiral artery remodeling during pregnancy. Our data suggest that LIF plays an important role in trophoblast invasion in vivo and may facilitate trophoblast-decidual-immune cell cross talk to enable adequate spiral artery remodeling.

  15. THE ROLES OF bcl-2 GENE FAMILY IN THE PULMONARY ARTERY REMODELING OF HYPOXIA PULMONARY HYPERTENSION IN RATS

    Institute of Scientific and Technical Information of China (English)

    杨成; 王胜发; 梁桃; 王巨; 王凯; 王柏春

    2001-01-01

    Objective. To investigate the roles of apoptosis in the pulmonary artery remodeling of pulmonary hypertension secondary to hypoxia and illustrate the relative genes expression.Methods. Thirty rats were divided into hypoxia group(10%O2, 8h/d) and normal control group. On the 15th day of hypoxia, pulmonary artery pressure and right ventricular hypertrophy index were measured and pulmonary artery vessels were studied by light microscope. Then terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)technique was used to detect nucleosomal DNA fragmentation of apoptotic cells.In situ hybridization and RT-PCR were used to detect the expression level of bcl-2 and bax.``Results. The pulmonary artery pressure and right ventricular hypertrophy index of hypoxia group were increased significantly, the pulmonary artery wall of hypoxic group become incrassate than control group. Apoptotic cells can be found in lung with hypoxia or without hypoxia. Compared with control group, apoptotic index of hypoxic group decreased significantly. Through the methods of in situ hybridization and RT-PCR, we found the expression of bcl-2 increased whereas bax decreased significantly in the hypoxic group.``Conclusion. The alternation in bcl-2 and bax expression induced by hypoxia play an important role in the pulmonary artery remodeling which is the main pathologic change of pulmonary hypertension secondary to hypoxia.

  16. THE ROLES OF bcl-2 GENE FAMILY IN THE PULMONARY ARTERY REMODELING OF HYPOXIA PULMONARY HYPERTENSION IN RATS

    Institute of Scientific and Technical Information of China (English)

    王巨; 王凯; 王柏春; 杨成; 王胜发; 梁桃

    2001-01-01

    Objective. To investigate the roles of apeptosis in the pulmonary artery remodeling of pulmonary hypertension secondary to hypoxia and illustrate the relative genes expression. Methods. Thirty rats were divided into hypoxia group(10%O2, 8h/d) and normal control group. On the 15th day of hypoxia, pulmonary artery pressure and fight ventricular hypertrophy index were measured and pulmonary artery vessels were studied by light microscope. Then terminal deoxynucleotidyl transferase-mediateddUTP nick-end labeling(TUNEL)technique was used to detect nucleosomal DNA fragmentation of apeptotic cells.In situ hybridization and RT-PCR were used to detect the expression level of bel-2 and bax. Results. The pulmonary artery pressure and right ventricular hypertrophy index of hypoxia group were increased significantly, the pulmonary artery wall of hypoxic group become incrassate than control group. Apeptotic cells can be found in lung with hypoxia or without hypexia. Compared with control group, apeptotic index of hypoxic group decreased significantly. Through the methods of in situ hybridization and RT-PCR, we found the expression of bel-2 increased whereas bax decreased significantly in the hypoxic group. Conclusion. The alternation in bel-2 and bax expression induced by hypoxia play an important role in the pulmonary artery remodeling which is the main pathologic change of p~monary hypertension secondary to hypoxia.

  17. Carotid thin fluttering bands: A new element of arterial wall remodelling? An ultrasound study.

    Science.gov (United States)

    Costanzo, Luca; Sole, Andrea; Tamburino, Corrado; Di Pino, Luigi

    2015-10-01

    Carotid artery ultrasound is a non-invasive and reproducible technique used for early atherosclerotic assessment. Intimal flap has been described in the presence of dissection or mobile plaque rupture, however presence of carotid thin fluttering bands (TFBs) have not been described yet. To investigate frequency, characteristics and impact of TFBs in carotid lumen of patients who underwent carotid ultrasound scan (CUS). 3341 patients were admitted from January 2009 to January 2014. Patients with history of cerebral ischemia (CI) were excluded. In the cases in which TFBs were observed, a 3-months clinical and CUS follow-up (FU) was performed. TFBs were found in 71 patients (2.1%). The mean age was 63.41 ± 11.20 years (range 42-89). All patients showed a mean increase in intima-media thickness. We identified two subgroups: in 22 patients the TFB was related to a carotid plaque while in 49 no carotid plaque was found. TFB mostly originated in the carotid bulb (88.7%) and was similarly located in carotid arteries (49.3% left-side and 50.7% right-side). CUS and clinical FU were available for all patients (mean duration 25.34 months, median 19). CI occurred in none of the patients. TFB disappeared in 13 patients (18.3%) with no sign or symptoms of CI. In 3 of 49 patients without carotid plaque (6.1%), progressive thickening beneath TFB was observed. TFB is a rare finding. Longer FU is needed to evaluate its prognosis. To date, the pathophysiology is unknown, however it could be related to vascular remodeling. PMID:26179862

  18. Early teatment with hepatocyte growth factor improves pulmonary artery and right ventricular remodeling in rats with pulmonary artery hypertension by modulating cytokines expression

    Institute of Scientific and Technical Information of China (English)

    王晓林

    2014-01-01

    Objective To investigate the effect of early treatment with hepatocyte growth factor(HGF)on the cytokine expression and pulmonary artery,right ventricular(RV)remodeling in the rat model of pulmonary artery hypertension(PAH).Methods The rat model of PAH was produced by injecting monocrotaline,and the model rats were randomly divided into empty adenovirus transfection group(MCT group,n=10)and HGF gene transfection group(HGF group,n=10).Another group of rats served as the Sham operation group(Sham group n=10).After 4 weeks of HGF gene transfection,the histological sections of the lungs and right ventricular(RV)

  19. Structural-functional State and feature remodeling of left ventricle in patients with coronary artery disease after revascularization

    OpenAIRE

    ALYAVI ANIS LUTFULLAEVICH; KAMILOVA UMIDA KABIROVNA; TULAGANOVA DILDORA KARIMOVNA; RADJABOVA DIYORA ISKANDAROVNA; SHODIEV JASUR DAVLATOVICH

    2016-01-01

    The article estimated the dynamics of systolic and diastolic function in patients with acute myocardial infarction after myocardial revascularization. The study involved 42 patients with acute myocardial infarction with ST segment elevation up to 6 hours of onset. Primary stenting of the infarct-related artery in patients with acute myocardial infarction with ST segment elevation allows most early as possible to prevent the development of pathological remodeling of the left ventricle compared...

  20. Trophoblast- and Vascular Smooth Muscle Cell-Derived MMP-12 Mediates Elastolysis during Uterine Spiral Artery Remodeling

    OpenAIRE

    Harris, Lynda K.; Smith, Samantha D.; Rosemary J Keogh; Jones, Rebecca L; Philip N Baker; Knöfler, Martin; Cartwright, Judith E.; Whitley, Guy St J; John D Aplin

    2010-01-01

    During the first trimester of pregnancy, the uterine spiral arteries are remodeled, creating heavily dilated conduits that lack maternal vasomotor control but allow the placenta to meet an increasing requirement for nutrients and oxygen. To effect permanent vasodilatation, the internal elastic lamina and medial elastin fibers must be degraded. In this study, we sought to identify the elastolytic proteases involved in this process. Primary first-trimester cytotrophoblasts (CTBs) derived from t...

  1. Pregnancy prevents hypertensive remodeling and decreases myogenic reactivity in posterior cerebral arteries from Dahl salt-sensitive rats : a role in eclampsia?

    NARCIS (Netherlands)

    Aukes, Annet M.; Vitullo, Lisa; Zeeman, Gerda G.; Cipolla, Marilyn J.

    2007-01-01

    Previous studies have demonstrated that pregnancy prevents protective hypertension-induced remodeling of cerebral arteries using nitric oxide synthase (NOS) inhibition to raise mean arterial pressure (MAP). In the present study, we investigated whether this effect of pregnancy was specific to NOS in

  2. Postlipolytic insulin-dependent remodeling of micro lipid droplets in adipocytes

    OpenAIRE

    Ariotti, Nicholas; Murphy, Samantha; Hamilton, Nicholas A; Wu, Lizhen; Green, Kathryn; Nicole L Schieber; Li, Peng; Martin, Sally; Parton, Robert G.

    2012-01-01

    Despite the lipolysis–lipogenesis cycle being a fundamental process in adipocyte biology, very little is known about the morphological changes that occur during this process. The remodeling of lipid droplets to form micro lipid droplets (mLDs) is a striking feature of lipolysis in adipocytes, but once lipolysis ceases, the cell must regain its basal morphology. We characterized mLD formation in cultured adipocytes, and in primary adipocytes isolated from mouse epididymal fat pads, in response...

  3. Maternal carotid remodeling and increased carotid arterial stiffness in normal late-gestational pregnancy as assessed by radio-frequency ultrasound technique

    OpenAIRE

    Yuan, Li-Jun; Xue, Dan; DUAN, YUN-YOU; Cao, Tie-Sheng; Zhou, Ning

    2013-01-01

    Background The adaption of elastic arteries to transient increase in hemodynamic load in normal pregnancy (NP) remains controversial. The purpose of this study was to investigate the NP carotid remodeling and regional arterial stiffness before and after parturition. Methods Fifty-one NP women and 30 age-matched non-pregnant women were included. All women underwent right common carotid artery (RCCA) measurements with MylabTwice ultrasound instrument (Esaote, Italy). Carotid intima-medial thick...

  4. AMPK Activation by Metformin Suppresses Abnormal Extracellular Matrix Remodeling in Adipose Tissue and Ameliorates Insulin Resistance in Obesity.

    Science.gov (United States)

    Luo, Ting; Nocon, Allison; Fry, Jessica; Sherban, Alex; Rui, Xianliang; Jiang, Bingbing; Xu, X Julia; Han, Jingyan; Yan, Yun; Yang, Qin; Li, Qifu; Zang, Mengwei

    2016-08-01

    Fibrosis is emerging as a hallmark of metabolically dysregulated white adipose tissue (WAT) in obesity. Although adipose tissue fibrosis impairs adipocyte plasticity, little is known about how aberrant extracellular matrix (ECM) remodeling of WAT is initiated during the development of obesity. Here we show that treatment with the antidiabetic drug metformin inhibits excessive ECM deposition in WAT of ob/ob mice and mice with diet-induced obesity, as evidenced by decreased collagen deposition surrounding adipocytes and expression of fibrotic genes including the collagen cross-linking regulator LOX Inhibition of interstitial fibrosis by metformin is likely attributable to the activation of AMPK and the suppression of transforming growth factor-β1 (TGF-β1)/Smad3 signaling, leading to enhanced systemic insulin sensitivity. The ability of metformin to repress TGF-β1-induced fibrogenesis is abolished by the dominant negative AMPK in primary cells from the stromal vascular fraction. TGF-β1-induced insulin resistance is suppressed by AMPK agonists and the constitutively active AMPK in 3T3L1 adipocytes. In omental fat depots of obese humans, interstitial fibrosis is also associated with AMPK inactivation, TGF-β1/Smad3 induction, aberrant ECM production, myofibroblast activation, and adipocyte apoptosis. Collectively, integrated AMPK activation and TGF-β1/Smad3 inhibition may provide a potential therapeutic approach to maintain ECM flexibility and combat chronically uncontrolled adipose tissue expansion in obesity. PMID:27207538

  5. Insulin

    Science.gov (United States)

    ... Short Acting Humulin N NPH Human Insulin (Human Insulin Isophane Suspension) Intermediate Acting Novolin N NPH Human Insulin (Human Insulin Isophane Suspension) Intermediate Acting Lantus Insulin Glargine Long Acting ...

  6. Lipogenesis in arterial wall and vascular smooth muscular cells: regulation and abnormalities in insulin-resistance

    Directory of Open Access Journals (Sweden)

    Feugier Patrick

    2009-12-01

    Full Text Available Abstract Background Vascular smooth muscular cells (VSMC express lipogenic genes. Therefore in situ lipogenesis could provide fatty acids for triglycerides synthesis and cholesterol esterification and contribute to lipid accumulation in arterial wall with aging and during atheroma. Methods We investigated expression of lipogenic genes in human and rat arterial walls, its regulation in cultured VSMC and determined if it is modified during insulin-resistance and diabetes, situations with increased risk for atheroma. Results Zucker obese (ZO and diabetic (ZDF rats accumulated more triglycerides in their aortas than their respective control rats, and this triglycerides content increased with age in ZDF and control rats. However the expression in aortas of lipogenic genes, or of genes involved in fatty acids uptake, was not higher in ZDF and ZO rats and did not increase with age. Expression of lipogenesis-related genes was not increased in human arterial wall (carotid endarterectomy of diabetic compared to non-diabetic patients. In vitro, glucose and adipogenic medium (ADM stimulated moderately the expression and activity of lipogenesis in VSMC from control rats. LXR agonists, but not PXR agonist, stimulated also lipogenesis in VSMC but not in arterial wall in vivo. Lipogenic genes expression was lower in VSMC from ZO rats and not stimulated by glucose or ADM. Conclusion Lipogenic genes are expressed in arterial wall and VSMC; this expression is stimulated (VSMC by glucose, ADM and LXR agonists. During insulin-resistance and diabetes, this expression is not increased and resists to the actions of glucose and ADM. It is unlikely that this metabolic pathway contribute to lipid accumulation of arterial wall during insulin-resistance and diabetes and thus to the increased risk of atheroma observed in these situations.

  7. Role of TGF beta signaling in Remodeling of Non-Coronary Artery Aneurysms in Kawasaki disease /

    OpenAIRE

    Lee, Aaron Ming

    2014-01-01

    Coronary artery aneurysms remain a life-threatening complication of Kawasaki disease (KD), the most common form of pediatric acquired heart disease in developed countries (1). Potentially life-threatening coronary artery aneurysms (CAA) develop in 25% of untreated children and 5% of children treated with high dose intravenous immunoglobulin during the acute phase of the self-limited vasculitis (2). Non-coronary artery aneurysms (NCAA) in extra-parenchymal, muscular arteries occur in a minorit...

  8. Potential Biomarkers of Insulin Resistance and Atherosclerosis in Type 2 Diabetes Mellitus Patients with Coronary Artery Disease

    OpenAIRE

    Sharifah Intan Qhadijah Syed Ikmal; Hasniza Zaman Huri; Shireene Ratna Vethakkan; Wan Azman Wan Ahmad

    2013-01-01

    Type 2 diabetes mellitus patients with coronary artery disease have become a major public health concern. The occurrence of insulin resistance accompanied with endothelial dysfunction worsens the state of atherosclerosis in type 2 diabetes mellitus patients. The combination of insulin resistance and endothelial dysfunction leads to coronary artery disease and ischemic heart disease complications. A recognized biological marker, high-sensitivity C-reactive protein, has been used widely to asse...

  9. Tau pathology-dependent remodelling of cerebral arteries precedes Alzheimer's disease-related microvascular cerebral amyloid angiopathy.

    Science.gov (United States)

    Merlini, Mario; Wanner, Debora; Nitsch, Roger M

    2016-05-01

    Alzheimer's disease (AD) is characterised by pathologic cerebrovascular remodelling. Whether this occurs already before disease onset, as may be indicated by early Braak tau-related cerebral hypoperfusion and blood-brain barrier (BBB) impairment found in previous studies, remains unknown. Therefore, we systematically quantified Braak tau stage- and cerebral amyloid angiopathy (CAA)-dependent alterations in the alpha-smooth muscle actin (α-SMA), collagen, and elastin content of leptomeningeal arterioles, small arteries, and medium-sized arteries surrounding the gyrus frontalis medialis (GFM) and hippocampus (HIPP), including the sulci, of 17 clinically and pathologically diagnosed AD subjects (Braak stage IV-VI) and 28 non-demented control subjects (Braak stage I-IV). GFM and HIPP paraffin sections were stained for general collagen and elastin with the Verhoeff-van Gieson stain; α-SMA and CAA/amyloid β (Aβ) were detected using immunohistochemistry. Significant arterial elastin degradation was observed from Braak stage III onward and correlated with Braak tau pathology (ρ = 0.909, 95 % CI 0.370 to 0.990, p leptomeningeal arteries is an early-onset, Braak tau pathology-dependent process unrelated to CAA and AD, which potentially may contribute to downstream CAA-dependent microvascular pathology in AD. PMID:26988843

  10. Successful endothelialization and remodeling of a cell-free small-diameter arterial graft in a large animal model.

    Science.gov (United States)

    Koobatian, Maxwell T; Row, Sindhu; Smith, Randall J; Koenigsknecht, Carmon; Andreadis, Stelios T; Swartz, Daniel D

    2016-01-01

    The large number of coronary artery bypass procedures necessitates development of off-the-shelf vascular grafts that do not require cell or tissue harvest from patients. However, immediate thrombus formation after implantation due to the absence of a healthy endothelium is very likely. Here we present the successful development of an acellular tissue engineered vessel (A-TEV) based on small intestinal submucosa that was functionalized sequentially with heparin and VEGF. A-TEVs were implanted into the carotid artery of an ovine model demonstrating high patency rates and significant host cell infiltration as early as one week post-implantation. At one month, a confluent and functional endothelium was present and the vascular wall showed significant infiltration of host smooth muscle cells exhibiting vascular contractility in response to vaso-agonists. After three months, the endothelium aligned in the direction of flow and the medial layer comprised of circumferentially aligned smooth muscle cells. A-TEVs demonstrated high elastin and collagen content as well as impressive mechanical properties and vascular contractility comparable to native arteries. This is the first demonstration of successful endothelialization, remodeling, and development of vascular function of a cell-free vascular graft that was implanted in the arterial circulation of a pre-clinical animal model. PMID:26561932

  11. Progressive vascular remodelling, endothelial dysfunction and stiffness in mesenteric resistance arteries in a rodent model of chronic kidney disease.

    Science.gov (United States)

    Quek, K J; Boyd, R; Ameer, O Z; Zangerl, B; Butlin, M; Murphy, T V; Avolio, A P; Phillips, J K

    2016-06-01

    Chronic kidney disease (CKD) and hypertension are co-morbid conditions both associated with altered resistance artery structure, biomechanics and function. We examined these characteristics in mesenteric artery together with renal function and systolic blood pressure (SBP) changes in the Lewis polycystic kidney (LPK) rat model of CKD. Animals were studied at early (6-weeks), intermediate (12-weeks), and late (18-weeks) time-points (n=21), relative to age-matched Lewis controls (n=29). At 12 and 18-weeks, LPK arteries exhibited eutrophic and hypertrophic inward remodelling characterised by thickened medial smooth muscle, decreased lumen diameter, and unchanged or increased media cross-sectional area, respectively. At these later time points, endothelium-dependent vasorelaxation was also compromised, associated with impaired endothelium-dependent hyperpolarisation and reduced nitric oxide synthase activity. Stiffness, elastic-modulus/stress slopes and collagen/elastin ratios were increased in 6 and 18-week-old-LPK, in contrast to greater arterial compliance at 12weeks. Multiple linear regression analysis highlighted SBP as the main predictor of wall-lumen ratio (r=0.536, Pdisease. PMID:26771067

  12. Large Artery Remodeling and Dynamics following Simulated Microgravity by Prolonged Head-Down Tilt Bed Rest in Humans

    Directory of Open Access Journals (Sweden)

    Carlo Palombo

    2015-01-01

    Full Text Available The effects of simulated microgravity on the static and dynamic properties of large arteries are still mostly unknown. The present study evaluated, using an integrated vascular approach, changes in structure and function of the common carotid and femoral arteries (CCA and CFA after prolonged head-down tilt bed rest (HDTBR. Ten healthy men were enrolled in a 5-week HDTBR study endorsed by the Italian Space Agency (ASI. Arterial geometry, flow, stiffness, and shear rate were evaluated by ultrasound. Local carotid pulse pressure and wave reflection were studied by applanation tonometry. After five weeks of HDTBR, CFA showed a decrease in lumen diameter without significant changes in wall thickness (IMT, resulting in an inward remodeling. Local carotid pulse pressure decreased and carotid-to-brachial pressure amplification increased. The ratio of systolic-to-diastolic volumetric flow in CFA decreased, whereas in CCA it tended to increase. Indices of arterial stiffness and shear rate did not change during HDTBR, either in CCA or CFA. In summary, prolonged HDTBR has a different impact on CCA and CFA structure and flow, probably depending on the characteristics of the vascular bed perfused.

  13. Role of TGF-β signaling in remodeling of noncoronary artery aneurysms in kawasaki disease

    OpenAIRE

    Lee, AM; Shimizu, C.; Oharaseki, T; K. Takahashi; Daniels, LB; Kahn, A.; Adamson, R.; Dembitsky, W; Gordon, JB; Burns, JC

    2015-01-01

    © 2015 Society for Pediatric Pathology. Coronary artery aneurysms (CAA) remain an important complication of Kawasaki disease (KD), the most common form of pediatric acquired heart disease in developed countries. Potentially life-threatening CAA develop in 25% of untreated children and 5% of children treated with highdose intravenous immunoglobulin during the acute phase of the self-limited vasculitis. Noncoronary artery aneurysms (NCAA) in extraparenchymal, muscular arteries occur in aminorit...

  14. Arterial stiffness in insulin resistance: The role of nitric oxide and angiotensin II receptors

    Directory of Open Access Journals (Sweden)

    Divina G Brillante

    2008-12-01

    Full Text Available Divina G Brillante1, Anthony J O’Sullivan1, Laurence G Howes21St. George Clinical School, University of New South Wales, Kogarah, NSW, Australia; 2Department of Pharmacology and Therapeutics and Department of Cardiology, Griffith and Bond University, Gold Coast Hospital, Southport, QLD, AustraliaAbstract: The insulin resistance syndrome (INSR is associated with increased cardiovascular risk, and affects up to 25% of the Australian population aged >20 years. Increased arterial stiffness has been proposed as a common pathway by which INSR leads to increased cardiovascular risk. We have reviewed the role of nitric oxide (NO and angiotensin II receptors in the modulation of arterial stiffness in the setting of insulin resistance. There is emerging evidence that early stages of INSR may be characterized by increased basal nitric oxide activity and increased activity of non-NO vasodilators such as endothelial derived hyperpolarization factor (EDHF which is manifest by reduced arterial stiffness. Depletion of NO or ineffectiveness of NO mediated vasodilator mechanisms associated with the progression of INSR to type 2 diabetes may result in increased arterial stiffness, which predicts the development of cardiovascular disease. Thus in the early stages of INSR, increased NO and EDHF activity may represent compensatory mechanisms to early vascular damage. The renin-angiotensin system is activated in diseased vascular beds, with up regulation of the two known angiotensin II receptors: the angiotensin II type 1 receptor (AT1R and the angiotensin II type 2 receptor (AT2R. Increased AT1R mediated activity in the vasculature is central to the development of increased arterial stiffness and is enhanced in INSR states. AT2R activity is increased in early in INSR and may contribute to the apparent increase in basal NO activity. AT1R blockade may therefore be valuable treatment for early INSR as antagonism of AT1 receptors would allow angiotensin II to act

  15. Effect of trimetazidine and glucose- insulin-potassium use on myocard during beating heart coronary artery bypass surgery

    OpenAIRE

    Ercan, Abdulkadir; Velioğlu, Yusuf; Ercan, Arzu; Gürbüz, Orçun; Özkan, Hakan; Karal, İlker Hasan; Biçer, Murat; Ener, Serdar

    2011-01-01

    Objectives: This prospective, randomised, controlled, clinical study was planned to determine the effect of trimetazidine and glucose - insulin - potassium (GIK) on myocardial ischemia-rep­erfusion during beating heart coronary artery bypass surgery. Materials and methods: Patients (n=45) with coronary artery disease who required beating heart coronary artery bypass grafting were randomly allocated into three groups. Patients in group 1 (n=15) was recevied trimetazidine (20 mg x 3...

  16. Effect of trimetazidine and glucose- insulin-potassium use on myocard during beating heart coronary artery bypass surgery

    OpenAIRE

    Abdulkadir Ercan; Yusuf Velioğlu; Arzu Ercan; Orçun Gürbüz; Hakan Özkan; İlker Hasan Karal; Murat Biçer; Serdar Ener

    2011-01-01

    Objectives: This prospective, randomised, controlled, clinical study was planned to determine the effect of trimetazidine and glucose - insulin - potassium (GIK) on myocardial ischemia-reperfusion during beating heart coronary artery bypass surgery.Materials and methods: Patients (n=45) with coronary artery disease who required beating heart coronary artery bypass grafting were randomly allocated into three groups. Patients in group 1 (n=15) was recevied trimetazidine (20 mg x 3 per day) 7 da...

  17. Need for insulin to control gestational diabetes is reflected in the ambulatory arterial stiffness index

    Directory of Open Access Journals (Sweden)

    Kärkkäinen Henna

    2013-01-01

    Full Text Available Abstract Background The aim was to evaluate the metabolic profile in conjunction with vascular function using the ambulatory arterial stiffness index (AASI in women with uncomplicated pregnancies and in women with gestational diabetes mellitus (GDM. Methods Plasma glucose, lipids, HOMA –IR (homeostasis model assessment of insulin resistance and AASI, as obtained from 24-hour ambulatory blood pressure monitoring in third trimester pregnancy and at three months postpartum, were measured in three groups of women: controls (N = 32, women with GDM on diet (N = 42 and women with GDM requiring insulin treatment (N = 10. Results Women with GDM had poorer glycemic control and higher HOMA-IR during and after pregnancy and their total and LDL (low density lipoprotein cholesterol levels were significantly higher after pregnancy than in the controls. After delivery, there was an improvement in AASI from 0.26 ± 0.10 to 0.17 ± 0.09 (P = 0.002 in women with GDM on diet, but not in women with GDM receiving insulin whose AASI tended to worsen after delivery from 0.30 ± 0.23 to 0.33 ± 0.09 (NS, then being significantly higher than in the other groups (P = 0.001-0.047. Conclusions Women with GDM had more unfavorable lipid profile and higher blood glucose values at three months after delivery, the metabolic profile being worst in women requiring insulin. Interestingly, the metabolic disturbances at three months postpartum were accompanied by a tendency towards arterial stiffness to increase in women requiring insulin.

  18. Increased oxidative stress and severe arterial remodeling induced by permanent high-flow challenge in experimental pulmonary hypertension

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    Fadel Elie

    2011-09-01

    Full Text Available Abstract Background Involvement of inflammation in pulmonary hypertension (PH has previously been demonstrated and recently, immune-modulating dendritic cells (DCs infiltrating arterial lesions in patients suffering from idiopathic pulmonary arterial hypertension (IPAH and in experimental monocrotaline-induced PH have been reported. Occurrence of perivascular inflammatory cells could be linked to local increase of oxidative stress (OS, as it has been shown for systemic atherosclerosis. The impact of OS on vascular remodeling in PH is still to be determined. We hypothesized, that augmented blood-flow could increase OS and might thereby contribute to DC/inflammatory cell-recruitment and smooth-muscle-cell-proliferation. Methods We applied a monocrotaline-induced PH-model and combined it with permanent flow-challenge. Thirty Sprague-Dawley rats were assigned to following groups: control, monocrotaline-exposure (MCT, monocrotaline-exposure/pneumonectomy (MCT/PE. Results Hemodynamic exploration demonstrated most severe effects in MCT/PE, corresponding in histology to exuberant medial and adventitial remodeling of pulmonary muscular arteries, and intimal remodeling of smaller arterioles; lung-tissue PCR evidenced increased expression of DCs-specific fascin, CD68, proinflammatory cytokines (IL-6, RANTES, fractalkine in MCT/PE and to a lesser extent in MCT. Major OS enzyme NOX-4 was maximal in MCT/PE. Antioxidative stress enzymes Mn-SOD and glutathion-peroxidase-1 were significantly elevated, while HO-1 showed maximal expression in MCT with significant decrease in MCT/PE. Catalase was decreased in MCT and MCT/PE. Expression of NOX-4, but also of MN-SOD in MCT/PE was mainly attributed to a highly increased number of interstitial and perivascular CXCR4/SDF1 pathway-recruited mast-cells. Stress markers malonedialdehyde and nitrotyrosine were produced in endothelial cells, medial smooth muscle and perivascular leucocytes of hypertensive vasculature

  19. Association of Insulin Resistance, Arterial Stiffness and Telomere Length in Adults Free of Cardiovascular Diseases.

    Directory of Open Access Journals (Sweden)

    Irina Strazhesko

    Full Text Available Chronic inflammation and oxidative stress might be considered the key mechanisms of aging. Insulin resistance (IR is a phenomenon related to inflammatory and oxidative stress. We tested the hypothesis that IR may be associated with cellular senescence, as measured by leukocyte telomere length (LTL, and arterial stiffness (core feature of arterial aging, as measured by carotid-femoral pulse wave velocity (c-f PWV.The study group included 303 subjects, mean age 51.8 ±13.3 years, free of known cardiovascular diseases and regular drug consumption. For each patient, blood pressure was measured, blood samples were available for biochemical parameters, and LTL was analyzed by real time q PCR. C-f PWV was measured with the help of SphygmoCor. SAS 9.1 was used for statistical analysis.Through multiple linear regression analysis, c-f PWV is independently and positively associated with age (p = 0.0001 and the homeostasis model assessment of insulin resistance (HOMA-IR; p = 0.0001 and independently negatively associated with LTL (p = 0.0378. HOMA-IR seems to have a stronger influence than SBP on arterial stiffness. In all subjects, age, HOMA-IR, LTL, and SBP predicted 32% of the variance in c-f PWV. LTL was inversely associated with HOMA-IR (p = 0.0001 and age (p = 0.0001. In all subjects, HOMA-IR, age, sex, and SBP predicted 16% of the variance in LTL.These data suggest that IR is associated with cell senescence and arterial aging and could, therefore, become the main target in preventing accelerated arterial aging, besides blood pressure control. Research in telomere biology may reveal new ways of estimating cardiovascular aging and risk.

  20. The effect of menopause on carotid artery remodeling, insulin sensitivity, and plasma adiponectin in healthy women

    DEFF Research Database (Denmark)

    Muscelli, Elza; Kozàkovà, Michaela; Flyvbjerg, Allan;

    2009-01-01

    secretion and sensitivity, plasma adiponectin), and carotid intima-media thickness (IMT) in healthy women. METHODS: In 74 menopausal women (mean age = 51 +/- 3 years, mean duration of menopause = 2.9 +/- 1.2 years) and in 74 nonmenopausal women comparable for age and body mass index (BMI), common carotid...... mathematical modeling. RESULTS: CCA diameter (5.55 +/- 0.46 vs. 5.21+/- 0.51 mm, P < 0.001), CCA IMT (608 +/- 78 vs. 576 +/- 74 microm, P < 0.01) and systolic blood pressure (BP) (117 +/- 12 vs. 113 +/- 11 mm Hg, P < 0.05) were higher in menopausal women, whereas CCA IMT/diameter ratio and IMT in other carotid...

  1. Fasudil, a Rho-kinase inhibitor, prevents intima-media thickening in a partially ligated carotid artery mouse model: Effects of fasudil in flow-induced vascular remodeling

    Science.gov (United States)

    Zhang, Xiangyu; Zhang, Tao; Gao, Fu; Li, Qingle; Shen, Chenyang; Li, Yankui; Li, Wei; Zhang, Xiaoming

    2015-01-01

    Vascular remodeling in response to hemodynamic alterations is a physiological process that requires coordinated signaling between endothelial, inflammatory and vascular smooth muscle cells (VSMCs). Extensive experimental and clinical studies have indicated the critical role of the Ras homolog gene family, member A/Rho-associated kinase (ROCK) signaling pathway in the pathogenesis of cardiovascular disease, where ROCK activation has been demonstrated to promote inflammation and remodeling through inducing the expression of proinflammatory cytokines and adhesion molecules in endothelial cells and VSMCs. However, the role of ROCK in flow-induced vascular remodeling has not been fully defined. The current study aimed to investigate the effect of the ROCK signaling pathway in flow-induced vascular remodeling by comparing the responses to partial carotid artery ligation in mice treated with fasudil (a ROCK inhibitor) and untreated mice. Intima-media thickness and neointima formation were evaluated by morphology. VSMC proliferation and inflammation of the vessel wall were assessed by immunohistochemistry. In addition, the expression levels of ROCK and the downstream effectors of ROCK, myosin light chain (MLC) and phosphorylated-MLC (p-MLC), were quantified by western blot analysis. Following a reduction in blood flow, ROCK1 and p-MLC expression increased in the untreated left common carotid arteries (LCA). Fasudil-treated mice developed a significantly smaller intima-media thickness compared with the untreated mice. Quantitative immunohistochemistry of the fasudil-treated LCA indicated that there was a reduction in proliferation when compared with untreated vessels. There were fewer CD45+ cells observed in the fasudil-treated LCA compared with the untreated LCA. In conclusion, the expression of ROCK was enhanced in flow-induced carotid artery remodeling and ROCK inhibition as a result of fasudil treatment may attenuate flow-induced carotid artery remodeling. PMID:26458725

  2. Auto-amplification of cortisol actions in human carotid atheroma is linked to arterial remodeling and stroke.

    Science.gov (United States)

    Ayari, Hanène; Legedz, Liliana; Lantelme, Pierre; Feugier, Patrick; Randon, Jacques; Cerutti, Catherine; Lohez, Olivier; Scoazec, Jean-Yves; Li, Jacques Yuan; Gharbi-Chihi, Jouda; Bricca, Giampiero

    2014-02-01

    High cortisol and aldosterone levels increase cardiovascular risk, but the respective roles of each hormone within the arterial wall remain controversial. We tested the hypothesis that cortisol production within the arterial wall may contribute to atherosclerotic remodeling and act through illicit activation of the mineralocorticoid receptor (MR). Gene expression studies of the corticoid system components and marker genes of the atherosclerotic process in human carotid atheroma plaque and nearby macroscopically intact tissue (MIT) were considered together with clinical data and compared with pharmacological stimulations of human vascular smooth muscle cells (VSMCs) in contractile or lipid-storing phenotypes. The components of corticoid production and action were present and active within the human carotid wall and VSMCs. Atheroma plaque and lipid-storing VSMCs expressed 11β-hydroxysteroid deshydrogenase-1 (11β-HSD1) at two- to tenfold higher levels than MIT or contractile VSMCs. The 11β-HSD1 expression was stimulated by cortisol and cortisone, especially in lipid-storing VSMCs. MR mRNA level was lower in atheroma and lipid-storing VSMCs and downregulated via MR by fludrocortisone and cortisol. Cortisol upregulated collagen1 and MCP-1 mRNAs via the glucocorticoid receptor (GRα), in both VSMC phenotypes, whereas fludrocortisone stimulated the collagen1 expression only in lipid-storing VSMCs. The GRα mRNA level in MIT was higher in patients with previous stroke and correlated positively with the collagen1 mRNA but negatively with diastolic blood pressure. Local cortisol production by 11β-HSD1, and its action via high parietal GRα could be relevant from the first step of atherosclerotic remodeling and auto-amplify with transdifferentiation of VSMCs during atheroma progression. PMID:23025717

  3. EFFECT OF INFLIXIMAB ON PARAMETERS OF REMODELING OF ARTERIAL BLOODSTREAM, RANKL AND OSTEOPROTEGERIN LEVELS IN PATIENTS WITH RHEUMATOID ARTHRITIS

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    Larisa Aleksandrovna Knyazeva

    2014-02-01

    Full Text Available Objective. To study the effect of infliximab (INF on serum levels of RANKL and osteoprotegerin (OPG, as well as on structural and functional properties of the vascular wall in patients with rheumatoid arthritis (RA.Material and Methods. A total of 79 RA patients who corresponded to the classification criteria ACR (1987 or ACR/EULAR (2010 and were seronegative for IgM rheumatoid factor (RF were examined. The mean age of patients was 43.6±8.5 years. The serum levels of OPG and RANKL were determined by ELISA (Biomedica, Austria; the common carotid arteries (CCAs were visualized using an Acuson X/10 ultrasonic complex equipped with a 7 MHz linear sensor in the β-mode prior to therapy and after 12-month therapy with INF.Results and Discussion. An increased OPG level was observed mostly in patients with RA duration up to 1 year; an increase in RANKL level was pronounced stronger in patients with PA duration over 2 years. The disturbance of structural and functional properties of the arterial bloodstream was revealed, manifesting itself as an increase in the intimamedia complex thickness, diameter and rigidity index of CCA that were stronger pronounced in patients with late onset RA. A correlation analysis showed the presence of reliable relationship between the RANKL and OPG levels and CCA remodeling parameters. INF therapy showed high clinical effectiveness and correction effect on the RANKL/OPG system. In addition, it was accompanied by a reduction of signs of CCA remodeling, which was stronger pronounced in patients with early RA.Conclusion. The results prove the reasonability of using INF at early stages of RA in order to optimize the therapy and achieve more efficient control of cardiovascular complications.

  4. Potential Biomarkers of Insulin Resistance and Atherosclerosis in Type 2 Diabetes Mellitus Patients with Coronary Artery Disease

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    Sharifah Intan Qhadijah Syed Ikmal

    2013-01-01

    Full Text Available Type 2 diabetes mellitus patients with coronary artery disease have become a major public health concern. The occurrence of insulin resistance accompanied with endothelial dysfunction worsens the state of atherosclerosis in type 2 diabetes mellitus patients. The combination of insulin resistance and endothelial dysfunction leads to coronary artery disease and ischemic heart disease complications. A recognized biological marker, high-sensitivity C-reactive protein, has been used widely to assess the progression of atherosclerosis and inflammation. Along with coronary arterial damage and inflammatory processes, high-sensitivity C-reactive protein is considered as an essential atherosclerosis marker in patients with cardiovascular disease, but not as an insulin resistance marker in type 2 diabetes mellitus patients. A new biological marker that can act as a reliable indicator of both the exact state of insulin resistance and atherosclerosis is required to facilitate optimal health management of diabetic patients. Malfunctioning of insulin mechanism and endothelial dysfunction leads to innate immune activation and released several biological markers into circulation. This review examines potential biological markers, YKL-40, alpha-hydroxybutyrate, soluble CD36, leptin, resistin, interleukin-18, retinol binding protein-4, and chemerin, as they may play significant roles in insulin resistance and atherosclerosis in type 2 diabetes mellitus patients with coronary artery disease.

  5. Pulsatile Tinnitus due to a Tortuous Siphon-Like Internal Carotid Artery Successfully Treated by Arterial Remodeling

    Directory of Open Access Journals (Sweden)

    Dirk De Ridder

    2013-01-01

    Full Text Available A patient is described with a right-sided tortuous siphon-like extracranial internal carotid artery leading to highly distressing ipsilateral heart beat synchronous pulsatile tinnitus, scoring 9/10 measuring loudness. Dilating the balloon during the occlusion test in or distal to the siphon-like anomaly reduces the arterial pulsations. Subsequently, surgery is performed using Teflon as an external construct to straighten the siphon-like anomaly. Postoperatively, the pulsations improve to 5/10 in a standing position and disappear during a reclined position. By adding a hearing aid, the pulsations are almost completely gone during a standing position (1/10 and remain absent in a reclined position.

  6. Nicotinamide Adenine Dinucleotide Phosphate Oxidase-Mediated Redox Signaling and Vascular Remodeling by 16α-Hydroxyestrone in Human Pulmonary Artery Cells: Implications in Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Hood, Katie Y; Montezano, Augusto C; Harvey, Adam P; Nilsen, Margaret; MacLean, Margaret R; Touyz, Rhian M

    2016-09-01

    Estrogen and oxidative stress have been implicated in pulmonary arterial hypertension (PAH). Mechanisms linking these systems are elusive. We hypothesized that estrogen metabolite, 16α-hydroxyestrone (16αOHE1), stimulates nicotinamide adenine dinucleotide phosphate oxidase (Nox)-induced reactive oxygen species (ROS) generation and proliferative responses in human pulmonary artery smooth muscle cells (hPASMCs) and that in PAH aberrant growth signaling promotes vascular remodeling. The pathophysiological significance of estrogen-Nox-dependent processes was studied in female Nox1(-/-) and Nox4(-/-) mice with PAH. PASMCs from control subjects (control hPASMCs) and PAH patients (PAH-hPASMCs) were exposed to estrogen and 16αOHE1 in the presence/absence of inhibitors of Nox, cytochrome P450 1B1, and estrogen receptors. Estrogen, through estrogen receptor-α, increased Nox-derived ROS and redox-sensitive growth in hPASMCs, with greater effects in PAH-hPASMCs versus control hPASMCs. Estrogen effects were inhibited by cytochrome P450 1B1 blockade. 16αOHE1 stimulated transient ROS production in hPASMCs, with sustained responses in PAH-hPASMCs. Basal expression of Nox1/Nox4 was potentiated in PAH-hPASMCs. In hPASMCs, 16αOHE1 increased Nox1 expression, stimulated irreversible oxidation of protein tyrosine phosphatases, decreased nuclear factor erythroid-related factor 2 activity and expression of nuclear factor erythroid-related factor 2-regulated antioxidant genes, and promoted proliferation. This was further amplified in PAH-hPASMCs. Nox1(-/-) but not Nox4(-/-) mice were protected against PAH and vascular remodeling. Our findings demonstrate that in PAH-hPASMCs, 16αOHE1 stimulates redox-sensitive cell growth primarily through Nox1. Supporting this, in vivo studies exhibited protection against pulmonary hypertension and remodeling in Nox1(-/-) mice. This study provides new insights through Nox1/ROS and nuclear factor erythroid-related factor 2 whereby 16αOHE1 influences

  7. Diet-induced hyperhomocysteinemia exacerbates vascular reverse remodeling of balloon-injured arteries in rat

    Institute of Scientific and Technical Information of China (English)

    GUO Yan-hong; CHEN Feng-ying; WANG Gui-song; CHEN Li; GAO Wei

    2008-01-01

    Background While hyperhomocysteinemia is associated with an increased risk of cardiovascular diseases,the effect of hyperhomocysteinemia on the vascular adventitia and vessel remodeling has not been clearly demonstrated.We investigated the effect of the hyperhomocysteinemia on adventitial hyperplasia and vascular remodeling following balloon injury in rats and the underlying mechanisms.Methods Rats were fed with diet containing methionine for 4 weeks to increase plasma homocysteine before balloon injury.Vascular geometrical changes were assessed at different time points following balloon injury.The collagen deposition was determined by picrosirius red staining and immunohistochemical staining.Results When compared with normal diet group,moderate hyperhomocysteinemia in methionine diet group significantly exacerbated adventitial hyperplasia at clay 7 and collagen deposition mainly in the adventitia at day 28 following balloon injury.The increased plasma homocysteine level significantly increased collagen deposition in the adventitia.There was a negative correlation (r=0.698;P <0.01) between the luminal area and the collagen content in the adventitia on day 28 following balloon injury.In cultured adventitial fibroblasts isolated from rat aorta,100 μmol/L L-homocysteine (L-Hcy) significantly down-regulated matrix metalloproteinase-2 activity by 43% as determined by in vitro gelatin zymography (P <0.05) and up-regulated the expression of collagen type 1 by 187% (P <0.05) assessed by Western blotting.Conclusions Hyperhomocysteinemia exacerbated vascular constrictive remodeling by accelerated neointima formation and collagen accumulation in the adventitia.Increased collagen deposition may be the underlying mechanism.

  8. The Possible Role of Extravillous Trophoblast-Derived Exosomes on the Uterine Spiral Arterial Remodeling under Both Normal and Pathological Conditions

    Directory of Open Access Journals (Sweden)

    Carlos Salomon

    2014-01-01

    Full Text Available A tenet of contemporary obstetrics is that events that compromise placentation increase the risk of complications of pregnancy and contribute to poor pregnancy outcome. In particular, conditions that affect the invasion of placental cells and remodeling of uterine spiral arteries compromise placental function and the subsequent development of the fetus. Extravillous trophoblast cells (EVTs proliferate and migrate from the cytotrophoblast in the anchoring villi of the placenta and invade the maternal decidua and myometrium. These cells are localised with uterine uterine spiral arteries and are thought to induce vascular remodeling. A newly identified pathway by which EVTs may regulate vascular remodeling within the uterus is via the release of exosomes. Trophoblast cells release exosomes that mediate aspects of cell-to-cell communication. The aim of this brief commentary is to review the putative role of exosomes released from extravillous trophoblast cells in uterine spiral artery remodeling and, in particular, their role in the aetiology of preeclampsia. Placental exosomes may engage in local cell-to-cell communication between the cell constituents of the placenta and contiguous maternal tissues and/or distal interactions, involving the release of placental exosomes into biological fluids and their transport to a remote site of action.

  9. Angioplasty and stenting for severe vertebral artery oriifce stenosis:effects on cerebellar function remodeling veriifed by blood oxygen level-dependent functional magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    Bo Liu; Zhiwei Li; Peng Xie

    2014-01-01

    Vertebral artery oriifce stenting may improve blood supply of the posterior circulation of the brain to regions such as the cerebellum and brainstem. However, previous studies have mainly focused on recovery of cerebral blood lfow and perfusion in the posterior circulation after inter-ventional therapy. This study examined the effects of functional recovery of local brain tissue on cerebellar function remodeling using blood oxygen level-dependent functional magnetic reso-nance imaging before and after interventional therapy. A total of 40 Chinese patients with severe unilateral vertebral artery oriifce stenosis were enrolled in this study. Patients were equally and randomly assigned to intervention and control groups. The control group received drug treat-ment only. The intervention group received vertebral artery oriifce angioplasty and stenting+identical drug treatment to the control group. At 13 days after treatment, the Dizziness Handicap Inventory score was compared between the intervention and control groups. Cerebellar function remodeling was observed between the two groups using blood oxygen level-dependent function-al magnetic resonance imaging. The improvement in dizziness handicap and cerebellar function was more obvious in the intervention group than in the control group. Interventional therapy for severe vertebral artery oriifce stenosis may effectively promote cerebellar function remodeling and exert neuroprotective effects.

  10. Chronic intrauterine pulmonary hypertension increases main pulmonary artery stiffness and adventitial remodeling in fetal sheep

    OpenAIRE

    Dodson, R. Blair; Morgan, Matthew R.; Galambos, Csaba; Hunter, Kendall S.; Abman, Steven H.

    2014-01-01

    Persistent pulmonary hypertension of the newborn (PPHN) is a clinical syndrome that is characterized by high pulmonary vascular resistance due to changes in lung vascular growth, structure, and tone. PPHN has been primarily considered as a disease of the small pulmonary arteries (PA), but proximal vascular stiffness has been shown to be an important predictor of morbidity and mortality in other diseases associated with pulmonary hypertension (PH). The objective of this study is to characteriz...

  11. Arterialization and anomalous vein wall remodeling in varicose veins is associated with upregulated FoxC2-Dll4 pathway.

    Science.gov (United States)

    Surendran, Sumi; S Ramegowda, Kalpana; Suresh, Aarcha; Binil Raj, S S; Lakkappa, Ravi Kumar B; Kamalapurkar, Giridhar; Radhakrishnan, N; C Kartha, Chandrasekharan

    2016-04-01

    Varicose veins of lower extremities are a heritable common disorder. Mechanisms underlying its pathogenesis are still vague. Structural failures such as valve weakness and wall dilatation in saphenous vein result in venous retrograde flow in lower extremities of body. Reflux of blood leads to distal high venous pressure resulting in distended veins. In an earlier study, we observed a positive association between c.-512C>T FoxC2 gene polymorphism and upregulated FoxC2 expression in varicose vein specimens. FoxC2 overexpression in vitro in venous endothelial cells resulted in the elevated mRNA expression of arterial endothelial markers such as Delta-like ligand 4 (Dll4) and Hairy/enhancer-of-split related with YRPW motif protein 2 (Hey2). We hypothesized that an altered FoxC2-Dll4 signaling underlies saphenous vein wall remodeling in patients with varicose veins. Saphenous veins specimens were collected from 22 patients with varicose veins and 20 control subjects who underwent coronary artery bypass grafting. Tissues were processed for paraffin embedding and sections were immunostained for Dll4, Hey2, EphrinB2, α-SMA, Vimentin, and CD31 antigens and examined under microscope. These observations were confirmed by quantitative real-time PCR and western blot analysis. An examination of varicose vein tissue specimens by immunohistochemistry indicated an elevated expression of Notch pathway components, such as Dll4, Hey2, and EphrinB2, and smooth muscle markers, which was further confirmed by gene and protein expression analyses. We conclude that the molecular alterations in Dll4-Hey2 signaling are associated with smooth muscle cell hypertrophy and hyperplasia in varicose veins. Our observations substantiate a significant role for altered FoxC2-Dll4 signaling in structural alterations of saphenous veins in patients with varicose veins. PMID:26808710

  12. JNKs, insulin resistance and inflammation: A possible link between NAFLD and coronary artery disease

    Institute of Scientific and Technical Information of China (English)

    Giovanni Tarantino; Armando Caputi

    2011-01-01

    The incidence of obesity has dramatically increased in recent years. Consequently, obesity and associated disorders such as nonalcoholic fatty liver disease constitute a serious problem. Therefore, the contribution of adipose tissue to metabolic homeostasis has become a focus of interest. In this review, we discuss the latest discoveries that support the role of lipids in nonalcoholic fatty liver disease. We describe the common mechanisms (c-Jun amino-terminal kinases, endoplasmic reticulum stress, unfolded protein response, ceramide, low-grade chronic inflammation) by which lipids and their derivatives impair insulin responsiveness and contribute to inflammatory liver and promote plaque instability in the arterial wall. Presenting the molecular mechanism of lipid activation of pro-inflammatory pathways, we attempt to find a link between nonalcoholic fatty liver disease, metabolic syndrome and cardiovascular diseases. Describing the common mechanisms by which lipid derivatives, through modulation of macrophage function, promote plaque instability in the arterial wall, impair insulin responsiveness and contribute to inflammatory liver and discussing the molecular mechanism of lipid activation of pro-inflammatory pathways, the key roles played by the proliferator-activated receptor and liver X receptor α, nuclear receptors-lipid sensors that link lipid metabolism and inflammation, should be emphasized. Further studies are warranted of anti-inflammatory drugs such as aspirin, anti-interleukin-6 receptors, immune-modulators (calcineurin inhibitors), substances enhancing the expression of heat shock proteins (which protect cells from endoplasmic reticulum stress-induced apoptosis), and anti- c-Jun amino-terminal kinases in well-designed trials to try to minimize the high impact of these illnesses, and the different expressions of the diseases, on the whole population.

  13. Role of TGF-β1/Smads pathway in carotid artery remodeling in renovascular hypertensive rats and prevention by Enalapril and Amlodipine

    Institute of Scientific and Technical Information of China (English)

    Jian-Ling Chen; Qian-Hui Shang; Wei Hu; Chan Liu; Wan-Heng Mao; Hua-Qing Liu

    2012-01-01

    Objective To investigate the role of transforming growth factor-β1 (TGF-β1), Smad2/3 and Smad7 expressions in carotid artery remodeling in renovascular hypertensive rats, and also the therapeutic effect of Enalapril and Amlodipine. Methods The renovascular hypertensive rat (RHR) models with "two-kidney and one-clip" were established, including model group (n = 6), sham-operated group (n = 6), Enalapril group (10 mg/kg per day, n = 6), Amlodipine group (5 mg/kg per day, n = 6) and combination group (Amlodipine 2.5 mg/kg per day + Enalapril 5mg/kg per day, n = 6). The medication were continuous administrated for six weeks. Carotid artery morphological and structural changes in the media were observed by HE staining, Masson staining and immuno histochemical staining. Media thickness (MT), MT and lumen diameter ratio (MT/LD), and the expression levels of media α-smooth muscle actin (α-actin), proliferating cell nuclear antigen (PCNA), TGF-β1, phosphorylated Smad2/3 (p-Smad2/3) and Smad7 in carotid arteries were measured. Results The media of carotid arteries in RHR model group was significantly thickened, the volume of smooth muscle cell was increased, and the array was in disorder; MT, MT/LD, the proliferation index of smooth muscle cell and collagen fiber area percentage of carotid arteries in the model group were significantly higher than those in the sham-operated group (P < 0.01). Compared to sham-operated group, the model group had significantly higher expressions of TGF-β1 and p-Smad2/3 (P < 0.05) and lower Smad7 expression. Both Enalapril and Amlodipine improved smooth muscle hypertrophy and collagen deposition, reduced RHR carotid MT, MT/LD, proliferation index of smooth muscle cell, collagen fiber area percentage and the expressions of TGF-β1 and p-Smad2/3 (P < 0.05), increased Smad7 expression (P < 0.05). Moreover, the combination treatment of Enalapril and Amlodipine had significantly better effects than single Amlodipine group (P < 0.05), but not

  14. A prospective study of glomerular filtration rate and arterial blood pressure in insulin-dependent diabetics with diabetic nephropathy

    DEFF Research Database (Denmark)

    Parving, H H; Smidt, U M; Friisberg, B; Bonnevie-Nielsen, V; Andersen, A R

    1981-01-01

    Glomerular filtration rate (GFR, single bolus 51Cr-EDTA technique), serum creatinine, proteinuria and arterial blood pressure have been measured prospectively in 14 young onset insulin-dependent diabetics selected by of persistent proteinuria (greater than 0.5 g/day) secondary to diabetic...... nephropathy. Twelve of the 14 patients had normal serum creatinine levels. None of the patients received antihypertensive treatment. During the mean observation period of 26 months (range 23 to 33 months) GFR decreased from 107 to 87 ml/min/1.73 m2 (p less than 0.001), serum creatinine remained unchanged: 107....../min/month (range 0.1 to 1.5 ml/min/month). The decrease in GFR did not correlate wih sex, age at onset, duration of diabetes, arterial blood pressure, proteinuria, insulin requirement, postprandial blood glucose or the initial GFR in each individual was constant, but varied considerably between patients. Increase...

  15. The orphan nuclear receptor Nur77 inhibits low shear stress-induced carotid artery remodeling in mice

    OpenAIRE

    Yu, Ying; Cai, Zhaohua; CUI, MINGLI; Nie, Peng; Sun, Zhe; SUN, SHIQUN; CHU, SHICHUN; Wang, Xiaolei; Hu, Liuhua; Yi, Jing; Shen, Linghong; He, Ben

    2015-01-01

    Shear stress, particularly low and oscillatory shear stress, plays a critical pathophysiological role in vascular remodeling-related cardiovascular diseases. Growing evidence suggests that the orphan nuclear receptor Nur77 [also known as TR3 or nuclear receptor subfamily 4, group A, member 1 (NR4A1)] is expressed in diseased human vascular tissue and plays an important role in vascular physiology and pathology. In the present study, we used a mouse model of flow-dependent remodeling by partia...

  16. Involvement of calcium-sensing receptors in hypoxia-induced vascular remodeling and pulmonary hypertension by promoting phenotypic modulation of small pulmonary arteries.

    Science.gov (United States)

    Peng, Xue; Li, Hong-Xia; Shao, Hong-Jiang; Li, Guang-Wei; Sun, Jian; Xi, Yu-Hui; Li, Hong-Zhu; Wang, Xin-Yan; Wang, Li-Na; Bai, Shu-Zhi; Zhang, Wei-Hua; Zhang, Li; Yang, Guang-Dong; Wu, Ling-Yun; Wang, Rui; Xu, Chang-Qing

    2014-11-01

    Phenotype modulation of pulmonary artery smooth muscle cells (PASMCs) plays an important role during hypoxia-induced vascular remodeling and pulmonary hypertension (PAH). We had previously shown that calcium-sensing receptor (CaSR) is expressed in rat PASMCs. However, little is known about the role of CaSR in phenotypic modulation of PASMCs in hypoxia-induced PAH as well as the underlying mechanisms. In this study, we investigated whether CaSR induces the proliferation of PASMCs in small pulmonary arteries from both rats and human with PAH. PAH was induced by exposing rats to hypoxia for 7-21 days. The mean pulmonary arterial pressure (mPAP), right ventricular hypertrophy index (RVI), the percentage of medial wall thickness to the external diameter (WT %), and cross-sectional total vessel wall area to the total area (WA %) of small pulmonary arteries were determined by hematoxylin and eosin (HE), masson trichrome and Weigert's staining. The protein expressions of matrix metalloproteinase (MMP)-2 and MMP-9, the tissue inhibitors of metalloproteinase (TIMP)-3, CaSR, proliferating cell nuclear antigen (PCNA), phosphorylated extracellular signal-regulated kinase (p-ERK), and smooth muscle cell (SMC) phenotype marker proteins in rat small pulmonary arteries, including calponin, SMα-actin (SMAα), and osteopontin (OPN), were analyzed by immunohistochemistry and Western blotting, respectively. In addition, immunohistochemistry was applied to paraffin-embedded human tissues from lungs of normal human and PAH patients with chronic heart failure (PAH/CHF). Compared with the control group, mPAP, RVI, WT % and WA % in PAH rats were gradually increased with the prolonged hypoxia. At the same time, the expressions of CaSR, MMP-2, MMP-9, TIMP-3, PCNA, OPN, and p-ERK were markedly increased, while the expressions of SMAα and calponin were significantly reduced in lung tissues or small pulmonary arteries of PAH rats. Neomycin (an agonist of CaSR) enhanced but NPS2390 (an

  17. AT1 receptor blockade attenuates insulin resistance and myocardial remodeling in rats with diet-induced obesity.

    Directory of Open Access Journals (Sweden)

    Silvio A Oliveira-Junior

    Full Text Available BACKGROUND: Although obesity has been associated with metabolic and cardiac disturbances, the carrier mechanisms for these responses are poorly understood. This study analyzed whether angiotensin II blockade attenuates metabolic and cardiovascular disorders in rats with diet-induced obesity. MATERIAL AND METHODS: Wistar-Kyoto (n = 40 rats were subjected to control (C; 3.2 kcal/g and hypercaloric diets (OB; 4.6 kcal/g for 30 weeks. Subsequently, rats were distributed to four groups: C, CL, OB, and OBL. L groups received Losartan (30 mg/kg/day for five weeks. After this period we performed in vivo glucose tolerance and insulin tolerance tests, and measured triacylglycerol, insulin, angiotensin-converting enzyme activity (ACE, and leptin levels. Cardiovascular analyzes included systolic blood pressure (SBP, echocardiography, myocardial morphometric study, myosin heavy chain composition, and measurements of myocardial protein levels of angiotensin, extracellular signal-regulated (ERK1/2, c-Jun amino-terminal kinases (JNK, insulin receptor subunit β (βIR, and phosphatidylinositol 3-kinase (PI3K by Western Blot. RESULTS: Glucose metabolism, insulin, lipid, and ACE activity disorders observed with obesity were minimized by Losartan. Moreover, obesity was associated with increased SBP, myocardial hypertrophy, interstitial fibrosis and improved systolic performance; these effects were also minimized with Losartan. On a molecular level, OB exhibited higher ERK, Tyr-phosphorylated βIR, and PI3K expression, and reduced myocardial angiotensin and JNK expression. ERK and JNK expression were regulated in the presence of Losartan, while angiotensin, Tyr-βRI, total and Tyr-phosphorylated PI3K expression were elevated in the OBL group. CONCLUSION: Angiotensin II blockade with Losartan attenuates obesity-induced metabolic and cardiovascular changes.

  18. MicroRNA-223 Attenuates Hypoxia-induced Vascular Remodeling by Targeting RhoB/MLC2 in Pulmonary Arterial Smooth Muscle Cells

    Science.gov (United States)

    Zeng, Yan; Zhang, Xiaoying; Kang, Kang; Chen, Jidong; Wu, Zhiqin; Huang, Jinyong; Lu, Wenju; Chen, Yuqin; Zhang, Jie; Wang, Zhiwei; Zhai, Yujia; Qu, Junle; Ramchandran, Ramaswamy; Raj, J. Usha; Wang, Jian; Gou, Deming

    2016-01-01

    There is growing evidence that microRNAs are implicated in pulmonary arterial hypertension (PAH), but underlying mechanisms remain elusive. Here, we identified that miR-223 was significantly downregulated in chronically hypoxic mouse and rat lungs, as well as in pulmonary artery and pulmonary artery smooth muscle cells (PASMC) exposed to hypoxia. Knockdown of miR-223 increased PASMC proliferation. In contrast, miR-223 overexpression abrogated cell proliferation, migration and stress fiber formation. Administering miR-223 agomir in vivo antagonized hypoxia-induced increase in pulmonary artery pressure and distal arteriole muscularization. RhoB, which was increased by hypoxia, was identified as one of the targets of miR-223. Overexpressed miR-223 suppressed RhoB and inhibited the consequent phosphorylation of myosin phosphatase target subunit (MYPT1) and the expression of myosin light chain of myosin II (MLC2), which was identified as another target of miR-223. Furthermore, serum miR-223 levels were decreased in female patients with PAH associated with congenital heart disease. Our study provides the first evidence that miR-223 can regulate PASMC proliferation, migration, and actomyosin reorganization through its novel targets, RhoB and MLC2, resulting in vascular remodeling and the development of PAH. It also highlights miR-223 as a potential circulating biomarker and a small molecule drug for diagnosis and treatment of PAH. PMID:27121304

  19. Effect of trimetazidine and glucose- insulin-potassium use on myocard during beating heart coronary artery bypass surgery

    Directory of Open Access Journals (Sweden)

    Abdulkadir Ercan

    2011-12-01

    Full Text Available Objectives: This prospective, randomised, controlled, clinical study was planned to determine the effect of trimetazidine and glucose - insulin - potassium (GIK on myocardial ischemia-reperfusion during beating heart coronary artery bypass surgery.Materials and methods: Patients (n=45 with coronary artery disease who required beating heart coronary artery bypass grafting were randomly allocated into three groups. Patients in group 1 (n=15 was recevied trimetazidine (20 mg x 3 per day 7 days before surgery. Patients in group 2 (n=15 received GIK infusion after induction of anesthesia through the first 12 hours of intensive care unit convalescence. Patients in group 3 (n=15 were control group. Measurements of blood glucose, circulating creatine kinase MB (CK-MB and Troponin I (TnI concentrations were obtained before surgery, 5 minutes after completion of operation and at 12, 24, and 48 hours postoperatively. Mean pulmonary artery pressure, cardiac index, morbidity and data associated with operation were recorded in all patients preoperatively and postoperatively.Results: Preoperative risk profiles and operative variables were statistically similar when the groups were compared. The concentration of circulating CK-MB and Tn I significantly increased over time after off - pump coronary artery surgery, with no significant intergroup differences. Cardiac index and mean pulmonary artery pressure did not differ significantly between groups.Conclusion: Pretreatment with trimetazidine and GIK infusion protocol were used as an adjunct to ischemic - reperfusion therapy in off - pump coronary artery bypass surgery. These results suggested that pretreatment with trimetazidine and GIK infusion protocol do not significantly reduce ischemic reperfusion damage.

  20. CLINICAL IMPORTANCE OF ENDOTHELIAL DYSFUNCTION AND INSULIN RESISTANCE SYNDROME IN PATIENTS WITH GOUT ASSOCIATED WITH ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    N. N. Kushnarenko

    2015-09-01

    Full Text Available Aim. To study the endothelium status and determine the correlation between endothelial dysfunction and glucose metabolism in men with gout associated with arterial hypertension (HT.Material and methods. Patients (n=175, all are males with gout were enrolled into the study. Ambulatory blood pressure monitoring (ABPM was performed in all patients. Endothelial function was studied in tests with reactive hyperemia (endothelium-dependent reaction and nitroglycerin (endothelium independent reaction in brachial artery by ultrasonic Doppler examination. The level of nitrite-nitrate and endothelin-1 in blood serum was determined by ELISA technique. Fasting blood glucose and oral glucose tolerance tests were performed as well as fasting insulin blood level was determined by immunoenzyme method. Insulin-resistance index (HOMA-IR was calculated. Patients with HOMA- IR>2.77 were considered as insulin-resistant.Results. Patients with gout demonstrated endothelial deterioration associated with activation of nitroxid producing function, elevation in endothelin-1 serum level (1.36 fmol/ml [0.91; 2.32 fmol/ml] vs 0.19 fmol/ml [0.16; 0.27 fmol/ml] in controls, p<0.05 and impairments of endothelium-dependent vasodilation (6.4% [3.3; 7.3%] vs 17.8% [12.7; 23.9%] in controls, p<0.05. The revealed changes were the most marked in patients with gout associated with HT. The correlation between some endothelial dysfunction in- dices and glucose metabolism was observed.Conclusion. ABPM, brachial artery endothelium-dependent vasodilation and glucose metabolism status should be studied in patients with gout. Complex treatment of cardiovascular diseases in patients with gout should include ω-3 polyunsaturated fatty acids, angiotensin receptor antagonists should be used for antihypertensive therapy.

  1. Experimental study of arterialized vein graft remodeling%静脉桥动脉化后桥血管重塑的实验研究

    Institute of Scientific and Technical Information of China (English)

    赵智伟; Abendroth DK; 葛建军; 林敏; 周正春; 王海涛; 孔祥; 刘永志; 邬松; 周经月

    2011-01-01

    Objective To investigate the effect of vein graft arterialization on vein graft remodeling.Methods Thirty SD rats were randomly divided into the AVG group and the CON group.We established vein graft arterialization model using inproved cuff technique in AVG group with the external jugular vein graft to the ipsilateral common carotid artery , but in CON group, only simulated surgical environment, cut and stitched the skin, separated artery and vein without the vein arterialization.Respectively, after 1 week, 2 weeks, 4 weeks vein grafts and the control veins were harvested, and intimal and medial hyperplasia were sdudied by morphological analysis.Results No animal died in two groups.There was only one case of vein occlusion in AVG group at 4 weeks, the patency rate was 93.3% .Intimal and medial of the AVG group were significantly thicker than those of the CON group (P <0.05 or P < 0.01) .Conclusion AVG advances the intimal and medial hyperplasia, and accelerates vein grafts remodeling.%目的 探讨静脉动脉化(AVG)对静脉桥血管结构重塑的影响.方法 将30只SD大鼠随机分为实验组和对照组.实验组采用改良cuff法构建颈AVG模型,对照组仅模拟手术环境,切开和缝合皮肤、分离动静脉,未进行AVG.分别于术后1、2、4周取出静脉桥及对照组颈静脉,进行形态学分析,研究桥血管内膜和中膜的增生变化.结果 2组模型均无动物死亡.4周时实验组1只闭塞,通畅率93.3%.实验组1、2、4周时内膜及中膜均较对照组增厚(P<0.05或<0.01).结论 AVG使静脉桥血管内膜及中膜增生,加快了静脉桥血管的结构重塑.

  2. Diet Induced Obesity Causes Cerebral Vessel Remodeling and Increases the Damage Caused by Ischemic Stroke

    OpenAIRE

    Deutsch, Christian; Portik-Dobos, Vera; Smith, Anita D; Ergul, Adviye; Dorrance, Anne M.

    2009-01-01

    Hypertension, elevated fasting blood glucose and plasma insulin develop in rats fed a high fat (HF) diet. Our goal was to assess the effects of obesity, beginning in childhood, on the adult cardiovascular system. We hypothesized that rats fed a HF diet would have larger ischemic cerebral infarcts and middle cerebral artery (MCA) remodeling. Three-week-old male Sprague Dawley rats were fed a HF (Obese) or control diet for 10 weeks. Cerebral ischemia was induced by MCA occlusion (MCAO). MCA str...

  3. Insulin resistance and associated dysfunction of resistance vessels and arterial hypertension

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren

    2005-01-01

    , calcitonin gene-related peptide, nitric oxide, and other vasodilators, and is most pronounced in the splanchnic area. This provides an effective (although relative) counterbalance to raised arterial blood pressure. Subjects with arterial hypertension (essential, secondary) may become normotensive during the...

  4. Short-Term Esmolol Improves Coronary Artery Remodeling in Spontaneously Hypertensive Rats through Increased Nitric Oxide Bioavailability and Superoxide Dismutase Activity

    Directory of Open Access Journals (Sweden)

    Ana Arnalich-Montiel

    2014-01-01

    Full Text Available The aim of this study was to assess the effects of short-term esmolol therapy on coronary artery structure and function and plasma oxidative stress in spontaneously hypertensive rats (SHR. For this purpose, 14-month-old male SHR were treated for 48 hours with esmolol (SHR-E, 300 μg/kg/min. Age-matched untreated male SHR and Wistar Kyoto rats (WKY were used as hypertensive and normotensive controls, respectively. At the end of intervention we performed a histological study to analyze coronary artery wall width (WW, wall-to-lumen ratio (W/L, and media cross-sectional area (MCSA. Dose-response curves for acetylcholine (ACh and sodium nitroprusside were constructed. We also assessed several plasma oxidative stress biomarkers, namely, superoxide scavenging activity (SOSA, nitrites, and total antioxidant capacity (TAC. We observed a significant reduction in WW (P<0.001, W/L (P<0.05, and MCSA (P<0.01 and improved endothelium-dependent relaxation (AUCSHR-E = 201.2±33 versus AUCSHR = 97.5±21, P<0.05 in SHR-E compared with untreated SHR; no differences were observed for WW, MCSA, and endothelium-dependent relaxation by ACh at higher concentrations (10−6 to 10−4 mol/l for SHR-E with respect to WKY. SOSA (P<0.001 and nitrite (P<0.01 values were significantly higher in SHR-E than in untreated SHR; however, TAC did not increase after treatment with esmolol. Esmolol improves early coronary artery remodeling in SHR.

  5. Adaptations to iron deficiency: cardiac functional responsiveness to norepinephrine, arterial remodeling, and the effect of beta-blockade on cardiac hypertrophy

    Directory of Open Access Journals (Sweden)

    Walker LeeAnn

    2002-01-01

    Full Text Available Abstract Background Iron deficiency (ID results in ventricular hypertrophy, believed to involve sympathetic stimulation. We hypothesized that with ID 1 intravenous norepinephrine would alter heart rate (HR and contractility, 2 abdominal aorta would be larger and more distensible, and 3 the beta-blocker propanolol would reduce hypertrophy. Methods 1 30 CD rats were fed an ID or replete diet for 1 week or 1 month. Norepinephrine was infused via jugular vein; pressure was monitored at carotid artery. Saline infusions were used as a control. The pressure trace was analyzed for HR, contractility, systolic and diastolic pressures. 2 Abdominal aorta catheters inflated the aorta, while digital microscopic images were recorded at stepwise pressures to measure arterial diameter and distensibility. 3 An additional 10 rats (5 ID, 5 control were given a daily injection of propanolol or saline. After 1 month, the hearts were excised and weighed. Results Enhanced contractility, but not HR, was associated with ID hypertrophic hearts. Systolic and diastolic blood pressures were consistent with an increase in arterial diameter associated with ID. Aortic diameter at 100 mmHg and distensibility were increased with ID. Propanolol was associated with an increase in heart to body mass ratio. Conclusions ID cardiac hypertrophy results in an increased inotropic, but not chronotropic response to the sympathetic neurotransmitter, norepinephrine. Increased aortic diameter is consistent with a flow-dependent vascular remodeling; increased distensibility may reflect decreased vascular collagen content. The failure of propanolol to prevent hypertrophy suggests that ID hypertrophy is not mediated via beta-adrenergic neurotransmission.

  6. Insulin resistance and associated dysfunction of resistance vessels and arterial hypertension

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren

    2005-01-01

    vascular resistance, high arterial compliance, increased cardiac output, secondary activation of counterregulatory systems (renin-angiotensin-aldosterone system, sympathetic nervous system, release of vasopressin), and resistance to vasopressors. The vasodilatory state is mediated through adrenomedullin...

  7. Influence of combined antihypertensive and antidepressant therapy on left ventricular remodeling in patients with arterial hypertension, anxiety and depression

    OpenAIRE

    Y. A. Vasyuk; T.V. Dovzenko; E.A. Nesterova; I.A. Sadulaeva; K.V. Tarasova

    2008-01-01

    Aim. To assess influence of combined antihypertensive (captopril or metoprolol) and antidepressant (thianeptin or sertralin) therapy on clinical status, blood pressure (BP) and myocardial function in patients with arterial hypertension (HT) and affective disorders (AD).Material and methods. 106 patients with HT were involved in the study. 64 patients (60,4%) had concomitant AD. All patients were divided into 3 groups. 46 patients with HT and AD were included in the 1-st group. They received m...

  8. Capabilities of Cluster Analysis in Interpretation of 24-Hour Blood Pressure Monitoring Data in Patients with Arterial Hypertension and Left Ventricular Remodeling

    Directory of Open Access Journals (Sweden)

    S.V. Samoyavcheva

    2015-12-01

    Full Text Available The aim of the investigation was to assess the potential of cluster analysis as an additional method of data analysis for 24-hour blood pressure monitoring (BPM in patients with both normal geometry and with various types and extents of remodeling of the left ventricle (LV. Materials and Methods. The investigation included 71 patients, ranging in age from 23 to 71. The inclusion criterion was significant arterial hypertension (AH, while exclusion criteria were symptomatic AH and severe co-morbidity. Body mass, height, waist measurement, body mass index, lipid profile, and glycemic level were determined for each subject in addition to carrying out echocardiography and conventional and cluster analysis of 24-hour BPM data of each. Results. In patient groups with different types of left ventricular hypertrophy (LVH, the conventional analysis demonstrated differences in the standard 24-hour BPM parameters. Development of concentric LVH is associated with the highest average day-time and average night-time blood pressure, pressure-induced loads and blood pressure variability. Eccentric LVH has a pathogenetic link to other factors and is formed under conditions of relatively low blood pressure. The use of cluster analysis allowed to reveal the increased occurrence of systolic-diastolic AH in concentric LVH, and isolated systolic AH and isolated diastolic AH in eccentric LVH. Conclusion. Such an integrated approach to the interpretation of 24-hour BPM results, comprising both conventional and cluster analysis, allows for objectification of the study results and reveals the significant features of AH in patients with different types of LV remodeling.

  9. Caloric restriction-associated remodeling of rat white adipose tissue: effects on the growth hormone/insulin-like growth factor-1 axis, sterol regulatory element binding protein-1, and macrophage infiltration

    OpenAIRE

    Chujo, Yoshikazu; Fujii, Namiki; Okita, Naoyuki; Konishi, Tomokazu; Narita, Takumi; Yamada, Atsushi; Haruyama, Yushi; Tashiro, Kosuke; Chiba, Takuya; Shimokawa, Isao; Higami, Yoshikazu

    2012-01-01

    The role of the growth hormone (GH)-insulin-like growth factor (IGF)-1 axis in the lifelong caloric restriction (CR)-associated remodeling of white adipose tissue (WAT), adipocyte size, and gene expression profiles was explored in this study. We analyzed the WAT morphology of 6–7-month-old wild-type Wistar rats fed ad libitum (WdAL) or subjected to CR (WdCR), and of heterozygous transgenic dwarf rats bearing an anti-sense GH transgene fed ad libitum (TgAL) or subjected to CR (TgCR). Although ...

  10. Impairment of the accumulation of decidual T cells, NK cells, and monocytes, and the poor vascular remodeling of spiral arteries, were observed in oocyte donation cases, regardless of the presence or absence of preeclampsia.

    Science.gov (United States)

    Nakabayashi, Yasushi; Nakashima, Akitoshi; Yoshino, Osamu; Shima, Tomoko; Shiozaki, Arihiro; Adachi, Tomoko; Nakabayashi, Masao; Okai, Takashi; Kushima, Miki; Saito, Shigeru

    2016-04-01

    In oocyte donation (OD) pregnancies, a fetus is a complete allograft to the maternal host and OD pregnancies are an independent risk factor for preeclampsia. Immunocompetent cells contribute to spiral artery remodeling and the failure of this process could contribute to the pathophysiology of preeclampsia. Recent data have shown that impaired autophagy of extravillous trophoblasts (EVT) may induce poor vascular remodeling in preeclampsia. We have studied the distribution of T cells, NK cells and macrophages in the decidua basalis of 14 normotensive OD pregnancies, 5 preeclamptic OD cases, 16 normotensive pregnancy cases, and 13 preeclamptic cases in natural pregnancy or autologous oocyte IVF-ET (NP/IVF). The populations of decidual CD3(+)T cells, CD8(+)T cells, CD4(+)T cells, Foxp3(+)Treg cells, CD56(+)NK cells, and CD68(+) macrophages in preeclampsia were significantly smaller than those in normal pregnancy in NP/IVF. Those frequencies in normotensive OD pregnancies or preeclamptic cases in OD pregnancies were similar to those in preeclamptic cases in NP/IVF. Impaired vascular remodeling was observed in OD pregnancies, regardless of the presence or absence of preeclampsia. The expression of p62, an impaired autophagy marker in EVT of normotensive or preeclamptic OD pregnancies, was significantly higher than that in normal pregnancies in NP/IVF. Immunological change in the decidua basalis and impairment of autophagy in EVT may induce impairment of spiral artery remodeling in OD pregnancies. PMID:26282090

  11. A randomized trial comparing the effect of weight loss and exercise training on insulin sensitivity and glucose metabolism in coronary artery disease

    DEFF Research Database (Denmark)

    Pedersen, Lene Rørholm; Olsen, Rasmus Huan; Jürs, Anders;

    2015-01-01

    AIM: The majority of patients with coronary artery disease (CAD) exhibit abnormal glucose metabolism, which is associated with mortality even at non-diabetic glucose levels. This trial aims to compare the effects of a considerable weight loss and exercise with limited weight loss on glucose...... followed by 2-4 weeks' weight maintenance diet. Glucose tolerance, insulin action, β-cell function and suppression of lipolysis were assessed using a 3-h oral glucose tolerance test. ISI-composite and ISI-HOMA (=1/HOMA-IR) were calculated as surrogate measures of whole-body and hepatic insulin sensitivity...

  12. INFLUENCE OF COMBINED ANTIHYPERTENSIVE AND ANTIDEPRESSANT THERAPY ON LEFT VENTRICULAR REMODELING IN PATIENTS WITH ARTERIAL HYPERTENSION, ANXIETY AND DEPRESSION

    Directory of Open Access Journals (Sweden)

    Y. A. Vasyuk

    2016-01-01

    Full Text Available Aim. To assess influence of combined antihypertensive (captopril or metoprolol and antidepressant (thianeptin or sertralin therapy on clinical status, blood pressure (BP and myocardial function in patients with arterial hypertension (HT and affective disorders (AD.Material and methods. 106 patients with HT were involved in the study. 64 patients (60,4% had concomitant AD. All patients were divided into 3 groups. 46 patients with HT and AD were included in the 1-st group. They received metoprolol or captopril in combination with tianeptine or sertaline. The 2-nd group included 18 patients with HT and AD who received only antihypertensive therapy. The 3-rd group consisted of 42 patients with HT without AD. They also received only antihypertensive therapy.Results. After 6 month therapy patients of the 1-st and the 3-rd groups had more significant clinical improvement and BP reduction (according to 24- hour BP monitoring as well as more farourable structural and functional changes of left ventricular in comparison with patients of the 2-nd group.Conclusion. In patients with HT and concomitant AD combined antihypertensive and antidepressant therapy result in favourable clinical changes, effectively reduce BP, improve left ventricular structure and function.

  13. Superior Mesenteric Artery Syndrome Complicated by Diabetic Ketoacidosis and Graves' Disease in Slowly Progressive Insulin Dependent Diabetes Mellitus (SPIDDM): A Case Report and a Review of the Literature.

    Science.gov (United States)

    Hirai, Hiroyuki; Fukushima, Naotaro; Hasegawa, Koji; Watanabe, Tsuyoshi; Hasegawa, Osamu; Satoh, Hiroaki

    2016-01-01

    A 48-year-old woman with a history of diabetes was admitted for nausea and vomiting with body weight loss. A blood examination revealed high plasma glucose and thyroid hormone levels and metabolic acidosis. She was therefore diagnosed with both diabetic ketoacidosis (DKA) and hyperthyroidism. Nausea and vomiting continued intermittently despite the administration of saline and insulin. The patient was further diagnosed with superior mesenteric artery syndrome (SMAS) after abdominal computed tomography revealed that a horizontal portion of the duodenum was sandwiched between the aorta and the superior mesenteric artery. Clinicians should be vigilant for SMAS in patients with both DKA and hyperthyroidism who present body weight loss. PMID:27477411

  14. Remodeling of Aorta Extracellular Matrix as a Result of Transient High Oxygen Exposure in Newborn Rats: Implication for Arterial Rigidity and Hypertension Risk

    Science.gov (United States)

    Castro, Michele M.; Cloutier, Anik; Bertagnolli, Mariane; Sartelet, Hervé; Germain, Nathalie; Comte, Blandine; Schulz, Richard; DeBlois, Denis; Nuyt, Anne Monique

    2014-01-01

    Neonatal high-oxygen exposure leads to elevated blood pressure, microvascular rarefaction, vascular dysfunction and arterial (aorta) rigidity in adult rats. Whether structural changes are present in the matrix of aorta wall is unknown. Considering that elastin synthesis peaks in late fetal life in humans, and early postnatal life in rodents, we postulated that transient neonatal high-oxygen exposure can trigger premature vascular remodelling. Sprague Dawley rat pups were exposed from days 3 to 10 after birth to 80% oxygen (vs. room air control) and were studied at 4 weeks. Blood pressure and vasomotor response of the aorta to angiotensin II and to the acetylcholine analogue carbachol were not different between groups. Vascular superoxide anion production was similar between groups. There was no difference between groups in aortic cross sectional area, smooth muscle cell number or media/lumen ratio. In oxygen-exposed rats, aorta elastin/collagen content ratio was significantly decreased, the expression of elastinolytic cathepsin S was increased whereas collagenolytic cathepsin K was decreased. By immunofluorescence we observed an increase in MMP-2 and TIMP-1 staining in aortas of oxygen-exposed rats whereas TIMP-2 staining was reduced, indicating a shift in the balance towards degradation of the extra-cellular matrix and increased deposition of collagen. There was no significant difference in MMP-2 activity between groups as determined by gelatin zymography. Overall, these findings indicate that transient neonatal high oxygen exposure leads to vascular wall alterations (decreased elastin/collagen ratio and a shift in the balance towards increased deposition of collagen) which are associated with increased rigidity. Importantly, these changes are present prior to the elevation of blood pressure and vascular dysfunction in this model, and may therefore be contributory. PMID:24743169

  15. Remodeling of aorta extracellular matrix as a result of transient high oxygen exposure in newborn rats: implication for arterial rigidity and hypertension risk.

    Directory of Open Access Journals (Sweden)

    Fanny Huyard

    Full Text Available Neonatal high-oxygen exposure leads to elevated blood pressure, microvascular rarefaction, vascular dysfunction and arterial (aorta rigidity in adult rats. Whether structural changes are present in the matrix of aorta wall is unknown. Considering that elastin synthesis peaks in late fetal life in humans, and early postnatal life in rodents, we postulated that transient neonatal high-oxygen exposure can trigger premature vascular remodelling. Sprague Dawley rat pups were exposed from days 3 to 10 after birth to 80% oxygen (vs. room air control and were studied at 4 weeks. Blood pressure and vasomotor response of the aorta to angiotensin II and to the acetylcholine analogue carbachol were not different between groups. Vascular superoxide anion production was similar between groups. There was no difference between groups in aortic cross sectional area, smooth muscle cell number or media/lumen ratio. In oxygen-exposed rats, aorta elastin/collagen content ratio was significantly decreased, the expression of elastinolytic cathepsin S was increased whereas collagenolytic cathepsin K was decreased. By immunofluorescence we observed an increase in MMP-2 and TIMP-1 staining in aortas of oxygen-exposed rats whereas TIMP-2 staining was reduced, indicating a shift in the balance towards degradation of the extra-cellular matrix and increased deposition of collagen. There was no significant difference in MMP-2 activity between groups as determined by gelatin zymography. Overall, these findings indicate that transient neonatal high oxygen exposure leads to vascular wall alterations (decreased elastin/collagen ratio and a shift in the balance towards increased deposition of collagen which are associated with increased rigidity. Importantly, these changes are present prior to the elevation of blood pressure and vascular dysfunction in this model, and may therefore be contributory.

  16. Enigma interacts with adaptor protein with PH and SH2 domains to control insulin-induced actin cytoskeleton remodeling and glucose transporter 4 translocation

    DEFF Research Database (Denmark)

    Barres, Romain; Grémeaux, Thierry; Gual, Philippe;

    2006-01-01

    and Glut 4 translocation without alterations in proximal insulin signaling. This inhibitory effect was prevented with the deletion of the LIM domains of Enigma. Using time-lapse fluorescent microscopy of green fluorescent protein-actin, we demonstrated that the overexpression of Enigma altered insulin......APS (adaptor protein with PH and SH2 domains) initiates a phosphatidylinositol 3-kinase-independent pathway involved in insulin-stimulated glucose transport. We recently identified Enigma, a PDZ and LIM domain-containing protein, as a partner of APS and showed that APS-Enigma complex plays...

  17. Restenosis and remodeling

    International Nuclear Information System (INIS)

    Percutaneous Transluminal Coronary Angioplasty (PTCA) remains limited by restenosis that occurs in 30 to 50% of patients with coronary artery disease. During the last decade, numerous agents have been used to prevent restenosis. Despite positive results in animal models, no pharmacological therapy has been found to significantly decrease the risk of restenosis in humans. These discrepancies between animal models and clinical situation were probably related to an incomplete understanding of the mechanism of restenosis. Neointimal thickening occurs in response to experimental arterial injury with a balloon catheter. Neointimal formation involves different steps: smooth muscle cell activation, proliferation and migration, and the production of extracellular matrix. The factors that control neointimal hyperplasia include growth factors humoral factors and mechanical factors. Arterial remodeling also plays a major role in the restenosis process. Studies performed in animal and human subjects have established the potentials for 'constrictive remodeling' to reduce the post-angioplasty vessel area, thereby indirectly narrowing the vessel lumen and thus contributing to restenosis. The reduction of restenosis rate in patients with intracoronary stent implantation has been attributed to the preventive effect of stent itself for this negative remodeling. In addition to these mechanism for restenosis, intraluminal or intra-plaque thrombus formation, reendothelialization and apoptosis theories have been introduced and confirmed at least in part

  18. Fasudil, a Rho-kinase inhibitor, prevents intima-media thickening in a partially ligated carotid artery mouse model: Effects of fasudil in flow-induced vascular remodeling

    OpenAIRE

    Zhang, Xiangyu; Zhang, Tao; Gao, Fu; Li, Qingle; Shen, Chenyang; Li, Yankui; Li, Wei; Zhang, Xiaoming

    2015-01-01

    Vascular remodeling in response to hemodynamic alterations is a physiological process that requires coordinated signaling between endothelial, inflammatory and vascular smooth muscle cells (VSMCs). Extensive experimental and clinical studies have indicated the critical role of the Ras homolog gene family, member A/Rho-associated kinase (ROCK) signaling pathway in the pathogenesis of cardiovascular disease, where ROCK activation has been demonstrated to promote inflammation and remodeling thro...

  19. Vascular insulin response is preserved in non-diabetic patients with coronary artery disease, despite endothelial dysfunction

    DEFF Research Database (Denmark)

    Ihlemann, Nikolaj; Rask-Madsen, Christian; Køber, Lars; Torp-Pedersen, Christian

    2004-01-01

    therefore studied the vascular insulin response in patients with CAD. MATERIALS AND METHODS--Nine non-diabetic patients with documented CAD and 31 lean healthy controls were examined. Forearm blood flow was measured by venous occlusion plethysmography. Dose-response studies of acetylcholine (ACh) and sodium...... response is intact in non-diabetic CAD patients in spite of insulin resistance and endothelial dysfunction....

  20. Insulin resistance reduces arterial prostacyclin synthase and eNOS activities by increasing endothelial fatty acid oxidation

    OpenAIRE

    DU, XUELIANG; Edelstein, Diane; Obici, Silvana; Higham, Ninon; Zou, Ming-Hui; Brownlee, Michael

    2006-01-01

    Insulin resistance markedly increases cardiovascular disease risk in people with normal glucose tolerance, even after adjustment for known risk factors such as LDL, triglycerides, HDL, and systolic blood pressure. In this report, we show that increased oxidation of FFAs in aortic endothelial cells without added insulin causes increased production of superoxide by the mitochondrial electron transport chain. FFA-induced overproduction of superoxide activated a variety of proinflammatory signals...

  1. Pharmacodynamic effects of oral contraceptive steroids on biochemical markers for arterial thrombosis. Studies in non-diabetic women and in women with insulin-dependent diabetes mellitus.

    Science.gov (United States)

    Petersen, Kresten Rubeck

    2002-02-01

    Even small increases in the frequency of thrombotic disease in users of OCs have general health impact because of their widespread use, which is currently expanding to potential risk groups. The present investigations were launched to study the effects of OCs containing 20-40 micrograms of EE combined with the latest developed gonane progestogens on biochemical risk markers within metabolic systems involved in the development of arterial thrombotic disease. The studies included evaluation of carbohydrate and lipid metabolism as well as the haemostatic system and were performed in non-diabetic women and in women with IDDM, who are prone to the development of arterial thrombosis. In the evaluation of the carbohydrate metabolism in non-diabetic women, we found no effect on fasting glucose or insulin and no effect on the insulin response to oral glucose in women using monophasic OCs containing EE combined with DSG or GST. This contrasts the evaluation of triphasic OCs containing EE combined with GST or NGT, which increased fasting insulin and reduced insulin sensitivity without affecting the glucose-effectiveness or the beta-cell function. Impaired glucose tolerance developed in 10% of the women after 6 months. These finding suggest that OCs are able to induce a state of insulin resistance, which should be considered in the prescription for women with potential disturbed insulin sensitivity or reduced beta-cell secretory capacity e.g. women with ovarian hyperandrogenism, obesity, previous GDM or perimenopausal women. We found no change in glycaemic control in 22 women with well-regulated IDDM treated with a monophasic combination of EE and GST for one year and none of the women developed microalbuminuria during treatment. In the women with diabetes we observed an increase in fasting levels of triglycerides, a decrease in LDL-cholesterol, and unchanged concentrations of total cholesterol and HDL-cholesterol during treatment. In non-diabetic women treated with the same

  2. Associations of metabolic variables with arterial stiffness in type 2 diabetes mellitus : focus on insulin sensitivity and postprandial triglyceridaemia

    NARCIS (Netherlands)

    van Dijk, RAJM; Bakker, SJL; Scheffer, PG; Heine, RJ; Stehouwer, CDA

    2003-01-01

    Background Type 2 diabetes mellitus is associated with an increased risk of atherothrombotic disease, which may in part be mediated through increased arterial stiffness. We investigated to what extent increased arterial stiffness is associated with cardiovascular risk factors that commonly cluster i

  3. Effect of renin-angiotensin -aldosterone system blockers on myocardial remodeling processes and risk for atrial fibrillation in patients with arterial hypertension

    Directory of Open Access Journals (Sweden)

    O. M. Drapkina

    2014-07-01

    Full Text Available The given review considers the mechanisms underlying the development and maintenance of atrial fibrillations (AF. It is noted that the processes of atrial fibrosis, ion channel remodeling, inflammation, apoptosis, impaired intercellular interactions, and myocardiocyte hypertrophy may give rise to atrial structural and functional changes in AF. The efficacy of angiotensinonverting enzyme inhibitors and angiotensin receptor antagonists is justified in patients with left ventricular systolic dysfunction.

  4. 胰岛素对大鼠心肌梗死后心室重构和心脏功能的影响及其机制%Effects of insulin on ventricular remodeling and cardiac functions after myocardial infarction and its underlying mechanism

    Institute of Scientific and Technical Information of China (English)

    韦广洪; 付锋; 马斌; 薛洋; 李嘉; 张利华

    2013-01-01

    目的:探讨胰岛素对大鼠心肌梗死(MI)后心室重构和心脏功能的影响及其机制.方法:80只成年雄性Sprague-Dawley大鼠行冠状动脉左前降支(LAD)结扎制备MI模型,随机分为5组:即假手术(Sham)组(n=20)、生理盐水对照(MI+ NS)组(n=20)、胰岛素治疗(MI+ Ins)组(n=20)、肿瘤坏死因子α(TNF-α)拮抗剂益赛普治疗(MI+ En)组(n=10)及Ins+ En治疗(MI+ Ins+ En)组(n=10).用ELISA法检测各组大鼠在MI后1周和4周时,心肌及血清TNF-α的水平.超声心动图测定各组大鼠左室射血分数(EF)、缩短分数(FS)和左心室舒张末内径(LVEDD)、左心室收缩末内径(LVESD)、经右颈总动脉插管测定血压(BP)、左室舒张压(LVDP)和最大左室舒张压/收缩压变化速率(±LVdp/dtmax).结果:大鼠MI后心肌中TNF-α增加,Ins治疗可明显降低大鼠心肌中TNF-α的含量(P<0.05,n=6).Ins治疗组大鼠EF、FS、LVDP和±LVdp/dtmax均明显高于对照组(P <0.05,n=10),LVESD明显低于对照组(P<0.05,n=10).与单独En治疗组相比,Ins+ En治疗组大鼠EF、FS、LVDP和±LVdp/dtmax明显升高、LVESD明显降低(P <0.05,n=10).结论:Ins可抑制MI后心室的扩张,改善心脏功能,但其机制不依赖于抑制心肌TNF-α的产生.%AIM: To investigate the effect of insulin treatment on ventricular remodeling and cardiac functions after myocardial infarction (MI) and the underlying mechanism. METHODS: MI models were established by ligation of the left anterior descending coronary artery (LAD). Eighty male adult Sprague Dawley rats were randomly divided into five groups: sham (n = 20) , MI + saline ( n = 20) , MI + insulin (n = 20) , MI + etanercept ( n = 10) , and MI + etanercept + insulin ( n = 10 ) . Serum and myocardial tumor necrosis factor-α (TNF-α) were measured at 1 week and 4 weeks after MI. Left ventricular (LV) fractional shortening ( FS) , ejection fraction ( EF) , LV end-diastolic diameter ( LVEDD) and end-systolic diameter (LVESD) were measured

  5. Insulin Resistance Promotes Early Atherosclerosis via Increased Proinflammatory Proteins and Oxidative Stress in Fructose-Fed ApoE-KO Mice

    Directory of Open Access Journals (Sweden)

    Beatriz Cannizzo

    2012-01-01

    Mice were fed with either a normal chow or a 10% w/v fructose (HF in drinking water over a period of 8 weeks. Thereafter, plasma metabolic parameters, vascular remodeling, atheroma lesion size, inflammatory markers, and NAD(PH oxidase activity in the arteries were determined. HF diet induced a marked increase in plasma glucose, insulin, and triglycerides in ApoE-KO mice, provoked vascular remodeling, enhanced expression of vascular cell-adhesion molecule-1 (VCAM-1 and matrix metalloprotease 9 (MMP-9 and enlarged atherosclerotic lesion in aortic and carotid arteries. NAD(PH oxidase activity was enhanced by fructose intake, and this effect was attenuated by tempol, a superoxide dismutase mimetic, and losartan, an Angiotensin II receptor antagonist. Our study results show that high-fructose-induced insulin resistance promotes a proinflammatory and prooxidant state which accelerates atherosclerotic plaque formation in ApoE-KO mice.

  6. Efeito da L-arginina na neoproliferação intimal e no remodelamento arterial após lesão por balão, em ilíacas de coelhos hipercolesterolêmicos The effect of L-arginine on neointimal proliferation and artery remodeling on an iliac artery lesion caused by a balloon catheter in hypercholesterolemic rabbits

    Directory of Open Access Journals (Sweden)

    José Knopfholz

    2006-10-01

    Full Text Available OBJETIVO: A neoproliferação intimal e o remodelamento têm sido implicados como os maiores fatores causadores de reestenose. O objetivo deste trabalho é estudar a ação da L-arginina por via oral, nesses dois fatores, após lesão por balão, em artérias ilíacas de coelhos hipercolesterolêmicos. MÉTODOS: Foram utilizados dezenove coelhos, que foram divididos em dois grupos: controle (GC e arginina (GA, respectivamente com dezenove e dezessete artérias estudadas. Os animais foram submetidos a lesão por balão de angioplastia, em suas artérias ilíacas, quinze dias após início de dieta hipercolesterolêmica a 2%. A seguir, os animais do GA passaram a receber uma solução de L-arginina, por via oral, na dose de 1 g/kg/dia. Após o sacrifício, no 15º dia após a lesão por balão, procedeu-se a cortes histológicos das artérias, as quais foram coradas e fixadas. Utilizou-se como representativa do desenvolvimento da lesão a razão da área da neoíntima (em mm² pela camada média (em mm². Por sua vez, a razão da área total do vaso em sua porção medial (de maior contato com o balão pela área total do vaso no segmento referencial (de menor contato com o balão foi a definidora do remodelamento. RESULTADOS: A média do espessamento neointimal (NI/M foi de 0,8151±0,2201 no GC e de 0,3296±0,1133 no GA. Não houve diferença entre os tipos de remodelamento entre os dois grupos estudados. CONCLUSÃO: No modelo experimental utilizado, a L-arginina foi capaz de reduzir o espessamento intimal em coelhos hipercolesterolêmicos e não teve ação sobre o remodelamento arterial.OBJECTIVE: It has been implied that neointimal proliferation and remodeling are the major causes of restenosis. The objective of this study is to assess the effect of orally administered L-arginine on these two factors in hypercholesterolemic rabbits that had suffered an injury to their iliac arteries caused by a catheter balloon. METHODS: The study included

  7. Early Onset Inflammation in Pre-Insulin-Resistant Diet-Induced Obese Rats Does Not Affect the Vasoreactivity of Isolated Small Mesenteric Arteries

    DEFF Research Database (Denmark)

    Blædel, Martin; Raun, Kirsten; Boonen, Harrie C M;

    2012-01-01

    myography, we tested the vascular function of isolated small mesenteric arteries. Results: DIO animals had significantly (p <0.05) increased body weight (721.2 ± 6.3 g) compared to age- and sex-matched controls (643.4 ± 14.6 g), as well as a significant increase (p <0.01) in body fat percentage (29.7 ± 1....... Our study aimed to investigate signs of inflammation and their relation to vascular dysfunction in rats receiving a high fat diet. Methods: Diet-induced obese (DIO) rats were used as a model since these rats exhibit a human pre-diabetic pathology. Oral glucose and insulin tolerance tests were......Background: Obesity is an increasing burden affecting developed and emerging societies since it is associated with an increased risk of diabetes and consequent cardiovascular complications. Increasing evidence points towards a pivotal role of inflammation in the etiology of vascular dysfunction...

  8. IGF-1 and Insulin Resistance Are Major Determinants of Common Carotid Artery Thickness in Morbidly Obese Young Patients.

    Science.gov (United States)

    Sirbu, Anca; Nicolae, Horia; Martin, Sorina; Barbu, Carmen; Copaescu, Catalin; Florea, Suzana; Panea, Cristina; Fica, Simona

    2016-03-01

    We assessed the relationship between insulin resistance, serum insulin-like growth factor 1 (IGF-1) levels, and common carotid intima-media thickness (CC-IMT) in morbidly obese young patients. A total of 249 patients (aged 37.9 ± 9.8 years, body mass index [BMI] 45.6 ± 8.3 kg/m(2)) were evaluated (metabolic tests, serum IGF-1 measurements, homeostasis model assessment-insulin resistance [HOMA-IR], and ultrasonographically assessed CC-IMT) in a research program for bariatric surgery candidates. After adjusting for age, gender, BMI, systolic blood pressure, uric acid, antihypertensive and lipid-lowering treatment, metabolic syndrome, and metabolic class, both HOMA-IR and IGF-1 z-score were significantly associated with CC-IMT. These results were confirmed in logistic regression analysis, in which age (β = 1.11, P = .001), gender (β = 3.19, P = .001), HOMA-IR (β = 1.221, P = .005), and IGF-1 z-score (β = 1.734, P = .009) were the only independent determinants of abnormal CC-IMT, presumably modulating the effect of the other risk factors included in the regression. Area under the receiver-operating characteristic curve for the model was 0.841 (confidence interval: 0.776-0.907; P insulin resistance and IGF-1 z-score are significantly associated with CC-IMT, independent of other major cardiovascular risk factors. PMID:26085193

  9. Acetylcholine and bradykinin enhance hypotension and affect the function of remodeled conduit arteries in SHR and SHR treated with nitric oxide donors

    Directory of Open Access Journals (Sweden)

    Gerová M.

    2005-01-01

    Full Text Available Discrepancy was found between enhanced hypotension and attenuated relaxation of conduit arteries in response to acetylcholine (ACh and bradykinin (BK in nitric oxide (NO-deficient hypertension. The question is whether a similar phenomenon occurs in spontaneously hypertensive rats (SHR with a different pathogenesis. Wistar rats, SHR, and SHR treated with NO donors [molsidomine (50 mg/kg or pentaerythritol tetranitrate (100 mg/kg, twice a day, by gavage] were studied. After 6 weeks of treatment systolic blood pressure (BP was increased significantly in experimental groups. Under anesthesia, the carotid artery was cannulated for BP recording and the jugular vein for drug administration. The iliac artery was used for in vitro studies and determination of geometry. Compared to control, SHR showed a significantly enhanced (P < 0.01 hypotensive response to ACh (1 and 10 µg, 87.9 ± 6.9 and 108.1 ± 5.1 vs 35.9 ± 4.7 and 64.0 ± 3.3 mmHg, and BK (100 µg, 106.7 ± 8.3 vs 53.3 ± 5.2 mmHg. SHR receiving NO donors yielded similar results. In contrast, maximum relaxation of the iliac artery in response to ACh was attenuated in SHR (12.1 ± 3.6 vs 74.2 ± 8.6% in controls, P < 0.01. Iliac artery inner diameter also increased (680 ± 46 vs 828 ± 28 µm in controls, P < 0.01. Wall thickness, wall cross-section area, wall thickness/inner diameter ratio increased significantly (P < 0.01. No differences were found in this respect among SHR and SHR treated with NO donors. These findings demonstrated enhanced hypotension and attenuated relaxation of the conduit artery in response to NO activators in SHR and in SHR treated with NO donors, a response similar to that found in NO-deficient hypertension.

  10. Apoptosis, cell proliferation and modulation of cyclin-dependent kinase inhibitor p21(cip1) in vascular remodelling during vein arterialization in the rat.

    Science.gov (United States)

    Borin, Thaiz Ferraz; Miyakawa, Ayumi Aurea; Cardoso, Leandro; de Figueiredo Borges, Luciano; Gonçalves, Giovana Aparecida; Krieger, Jose Eduardo

    2009-06-01

    Neo-intima development and atherosclerosis limit long-term vein graft use for revascularization of ischaemic tissues. Using a rat model, which is technically less challenging than smaller rodents, we provide evidence that the temporal morphological, cellular, and key molecular events during vein arterialization resemble the human vein graft adaptation. Right jugular vein was surgically connected to carotid artery and observed up to 90 days. Morphometry demonstrated gradual thickening of the medial layer and important formation of neo-intima with deposition of smooth muscle cells (SMC) in the subendothelial layer from day 7 onwards. Transmission electron microscopy showed that SMCs switch from the contractile to synthetic phenotype on day 3 and new elastic lamellae formation occurs from day 7 onwards. Apoptosis markedly increased on day 1, while alpha-actin immunostaining for SMC almost disappeared by day 3. On day 7, cell proliferation reached the highest level and cellular density gradually increased until day 90. The relative magnitude of cellular changes was higher in the intima vs. the media layer (100 vs. 2 times respectively). Cyclin-dependent kinase inhibitors (CDKIs) p27(Kip1) and p16(INKA) remained unchanged, whereas p21(Cip1) was gradually downregulated, reaching the lowest levels by day 7 until day 90. Taken together, these data indicate for the first time that p21(Cip1) is the main CDKI protein modulated during the arterialization process the rat model of vein arterialization that may be useful to identify and validate new targets and interventions to improve the long-term patency of vein grafts. PMID:19563615

  11. Short-Term Esmolol Improves Coronary Artery Remodeling in Spontaneously Hypertensive Rats through Increased Nitric Oxide Bioavailability and Superoxide Dismutase Activity

    OpenAIRE

    Arnalich-Montiel, Ana; González, María Carmen; Delgado-Baeza, Emilio; Delgado-Martos, María Jesús; Condezo-Hoyos, Luis; Martos-Rodríguez, Antonia; Rodríguez-Rodríguez, Pilar; Quintana-Villamandos, Begoña

    2014-01-01

    The aim of this study was to assess the effects of short-term esmolol therapy on coronary artery structure and function and plasma oxidative stress in spontaneously hypertensive rats (SHR). For this purpose, 14-month-old male SHR were treated for 48 hours with esmolol (SHR-E, 300  μ g/kg/min). Age-matched untreated male SHR and Wistar Kyoto rats (WKY) were used as hypertensive and normotensive controls, respectively. At the end of intervention we performed a histological study to analyze coro...

  12. Short-Term Esmolol Improves Coronary Artery Remodeling in Spontaneously Hypertensive Rats through Increased Nitric Oxide Bioavailability and Superoxide Dismutase Activity

    OpenAIRE

    Ana Arnalich-Montiel; María Carmen González; Emilio Delgado-Baeza; María Jesús Delgado-Martos; Luis Condezo-Hoyos; Antonia Martos-Rodríguez; Pilar Rodríguez-Rodríguez; Begoña Quintana-Villamandos

    2014-01-01

    The aim of this study was to assess the effects of short-term esmolol therapy on coronary artery structure and function and plasma oxidative stress in spontaneously hypertensive rats (SHR). For this purpose, 14-month-old male SHR were treated for 48 hours with esmolol (SHR-E, 300 μg/kg/min). Age-matched untreated male SHR andWistar Kyoto rats (WKY) were used as hypertensive and normotensive controls, respectively. At the end of intervention we performed a histological study to analyz...

  13. The Associations of High-Density Lipoprotein Subclasses With Insulin and Glucose Levels, Physical Activity, Resting Heart Rate, and Regional Adiposity in Men With Coronary Artery Disease: The Stanford Coronary Risk Intervention Project Baseline Survey

    OpenAIRE

    Williams, Paul T.; Haskell, William L; Vranizan, Karen M; Ronald M. Krauss

    1995-01-01

    We used nondenaturing polyacrylamide gradient gel electrophoresis to examine the associations of high-density lipoprotein (HDL) subclasses with adiposity, physical activity, resting heart rate (an indicator of sympathetic drive), and plasma insulin and glucose levels in 97 men with angiographically documented coronary artery disease. These men neither smoked nor used medications known to affect lipoproteins. The absorbency of protein stain was used as an index of mass concentrations at interv...

  14. Determination of arterial wall shear stress

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The arteries can remodel their structure and function to adapt themselves to the mechanical environment. In various factors that lead to vascular remodeling, the shear stress on the arterial wall induced by the blood flow is of great importance. However, there are many technique difficulties in measuring the wall shear stress directly at present. In this paper, through analyzing the pulsatile blood flow in arteries, a method has been proposed that can determine the wall shear stress quantitatively by measuring the velocity on the arterial axis, and that provides a necessary means to discuss the influence of arterial wall shear stress on vascular remodeling.

  15. Coronary microvascular function, insulin sensitivity and body composition in predicting exercise capacity in overweight patients with coronary artery disease

    DEFF Research Database (Denmark)

    Jürs, Anders; Pedersen, Lene Rørholm; Olsen, Rasmus Huan; Snoer, Martin; Chabanova, Elizaveta; Haugaard, Steen Bendix; Prescott, Eva

    2015-01-01

    BACKGROUND: Coronary artery disease (CAD) has a negative impact on exercise capacity. The aim of this study was to determine how coronary microvascular function, glucose metabolism and body composition contribute to exercise capacity in overweight patients with CAD and without diabetes. METHODS......: Sixty-five non-diabetic, overweight patients with stable CAD, BMI 28-40 kg/m(2) and left ventricular ejection fraction (LVEF) above 35 % were recruited. A 3-hour oral glucose tolerance test was used to evaluate glucose metabolism. Peak aerobic exercise capacity (VO2peak) was assessed by a...... cardiopulmonary exercise test. Body composition was determined by whole body dual-energy X-ray absorptiometry scan and magnetic resonance imaging. Coronary flow reserve (CFR) assessed by transthoracic Doppler echocardiography was used as a measure of microvascular function. RESULTS: Median BMI was 31.3 and 72...

  16. Vascular Function, Insulin Action and Exercise: An Intricate Interplay

    OpenAIRE

    Zheng, Chao; Liu, Zhenqi

    2015-01-01

    Insulin enhances the compliance of conduit arteries, relaxes resistance arterioles to increase tissue blood flow and dilates precapillary arterioles to expand muscle microvascular blood volume. These actions are impaired in the insulin resistant states. Exercise ameliorates endothelial dysfunction and improves insulin responses in insulin resistant patients, but the precise underlying mechanisms remain unclear. The microvasculature critically regulates insulin action in muscle by modulating i...

  17. Growth hormone and insulin-like growth factor-1 in prognosis coronary artery disease in patients with obesity

    Directory of Open Access Journals (Sweden)

    Olga Viktorovna Shpagina

    2014-10-01

    Full Text Available Introduction. In patients with obesity coronary atherosclerosis and chronic heart failure (CHF progress rapidly and have a worse long-term prognosis than those with normal weight.Objective: To investigate the prognostic significance of GH and IGF-1 in the evaluation of cardiovascular risk in patients with obesity.Materials and Methods. The study included 75 men (mean age 55.31±6.32 years, which are overweight or have mild obesity (body mass index (BMI 28.69±3.6 kg/m2. Group 1 included 45 patients (age 56.4±6.29 years, BMI 28.69±3.69 kg/m2, blood pressure 124±10.18/80±4.59 mm Hg who underwent coronary angiography. Group 2 included 30 patients (mean age 53.6 ± 6.1 years, BMI 28.68±3.52 kg/m2, blood pressure 128±9/83±6.81 mm Hg, CAD who are excluded by treadmill test. The coronary artery calcium score was assessed in group 2. All participants were evaluated impaired glucose tolerance (IGT, triglycerides (TG, IGF-1 and GH, LPHD, LPLD, geometry of the heart chambers was assessed by echocardiography.Results. Patients in both groups did not differ in age, BMI, blood pressure. IGF-1 levels were not significantly different among the study groups. High circulating IGF-1 levels were frequently observed in group 1 (р=0.018. A statistically significant association of high IGF-1 observed with obesity (p=0.033, smoking (p=0.049, hypertension (p=0.002, end-diastolic dimension (p=0.045. GH was lower in group 1 compared with group 2 (p=0.046. Serum levels of GH are positively associated with EF (p=0.023 and E/A (p=0.043 and negatively associated with left atrial wall thickness (p=0.025 and coronary artery calcium score (p=0.005.Conclusion: 1. IGF-1 may be a useful indicator to assess the prognosis of CAD and CHF in patients with obesity. 2. Relative GH deficiency was more often associated with severe CAD in patients with obesity.

  18. Influence of insulin resistance on long-term outcomes in patients with coronary artery disease after sirolimus-eluting stent implantation

    Institute of Scientific and Technical Information of China (English)

    ZHAO Liang-ping; L(U) An-kang; SHEN Wei-feng; LIU Hai-feng; MA Xiao-ye; FAN Xiao-ming; ZHANG Qi

    2010-01-01

    Background Insulin resistance(IR)is significantly associated with coronary artery disease and cardiovascular events in patients with or without type 2 diabetes mellitus.This study aimed to evaluate the influence of IR on long-term outcomes of patients undergoing percutaneous coronary intervention(PCI)with sirolimus-eluting stent(SES)implantation.Methods A total of 467 consecutive patients undergoing SES-based PCI were divided into lR group(n=104)and non-IR group(n=363).The patients were followed up for one year.The rate of major adverse cardiac events(MACEs) including death, non-fatal myocardial infarction and recurrent angina pectoris was compared by the log-rank test,and the independent risk factors were identified by the Cox regression analysis.Results MACEs occurred more frequently,and cumulative survival rate was lower in the IR group than in the non-IR group during the follow-up (all P<0.05).IR was an independent risk factor for the occurrence of cardiac death and non-fatal myocardial infarction(OR=2176,95% CI=1.35-5.47,P=0.034).Old age,diabetes,and multi-vessel disease were determinants for recurrent angina pectoris after PCI(P<0.05).Subgroup analysis revealed that IR(OR=3.35,95% CI=1.07-13.59,P=0.013)and multi-vessel disease(OR=2.19,95%CI=1.01-5.14,P=0.044)were independent risk predictors for recurrent angina pectoris in patients with diabetes after PCI.Conclusions IR is associated with reduced MACE-free survival and remains an independent predictor for recurrent angina pectoris after PCI with SES implantation.

  19. Vascular Remodeling in Experimental Hypertension

    Directory of Open Access Journals (Sweden)

    Norma R. Risler

    2005-01-01

    Full Text Available The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts and noncellular (extracellular matrix components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

  20. Insulin Secretagogues

    Science.gov (United States)

    ... Your Body in Balance › Insulin Secretagogues Fact Sheet Insulin Secretagogues March, 2012 Download PDFs English Espanol Editors ... medicines can help you stay healthy. What are insulin secretagogues? Insulin secretagogues (pronounced seh-KREET-ah-gogs) ...

  1. Vascular progenitor cells in arterial remodeling

    OpenAIRE

    Grudzinska, Monika K.

    2011-01-01

    Cardiovascular disease is the leading cause of global mortality and physical disability mainly due to the complications such as myocardial infarction or stroke. Physiological healing reaction takes place in the diseased vessel wall aimed to repair the vessel after an injury. There are two factors essentially important for clinical improvement of vascular diseases. The first one is protection of the vascular damage, and the second one is repair of injured, ischemic and regenerating tissues to ...

  2. Insulin Test

    Science.gov (United States)

    ... especially as a result of taking non-human (animal or synthetic) insulin, these can interfere with insulin testing. In this case, a C-peptide may be performed as an alternative way to evaluate insulin production. Note also that ...

  3. Involvement of peroxisome proliferator-activated receptors in cardiac and vascular remodeling in a novel minipig model of insulin resistance and atherosclerosis induced by consumption of a high-fat/cholesterol diet

    OpenAIRE

    Yongming, Pan; Zhaowei, Cai; Yichao, Ma; Keyan, Zhu; Liang, Chen; Fangming, Chen; Xiaoping, Xu; Quanxin, Ma; Minli, Chen

    2015-01-01

    Background A long-term high-fat/cholesterol (HFC) diet leads to insulin resistance (IR), which is associated with inflammation, atherosclerosis (AS), cardiac sympathovagal imbalance, and cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) and nuclear factor ĸB (NF-κB) are involved in the development of IR-AS. Thus, we elucidated the pathological molecular mechanism of IR-AS by feeding an HFC diet to Tibetan minipigs to induce IR and AS. Methods Male Tibetan minipigs were ...

  4. Mechanism of the Susceptibility of Remodeled Pulmonary Vessels to Drug‐Induced Cell Killing

    OpenAIRE

    Ibrahim, Yasmine F.; Wong, Chi‐Ming; Pavlickova, Ludmila; Liu, Lingling; Trasar, Lobsang; Bansal, Geetanjali; Suzuki, Yuichiro J.

    2014-01-01

    Background Pulmonary arterial hypertension remains a devastating disease without a cure. The major complication of this disease is the abnormal growth of vascular cells, resulting in pulmonary vascular remodeling. Thus, agents, which affect the remodeled vessels by killing unwanted cells, should improve treatment strategies. The present study reports that antitumor drugs selectively kill vascular cells in remodeled pulmonary vessels in rat models of pulmonary hypertension. Methods and Results...

  5. Positive Vascular Remodeling in Culprit Coronary Lesion is Associated With Plaque Composition: An Intravascular Ultrasound-Virtual Histology Study

    OpenAIRE

    Lee, Chung Seop; Seo, Young Hoon; Yang, Dong Ju; Kim, Ki Hong; Park, Hyun Woong; Yuk, Hyung Bin; Lee, Moo-Sik; Kim, Wan-Ho; Kwon, Taek-Geun; Bae, Jang-Ho

    2012-01-01

    Background and Objectives The relationship between the positive remodeling (PR) of a coronary artery and plaque composition has been studied only in a relatively small number of study population or non-culprit lesion. We evaluated the association between coronary plaque composition and coronary artery remodeling in a relatively large number of culprit lesions. Subjects and Methods The study population consisted of 325 consecutive patients with coronary artery disease that underwent intravascu...

  6. Nitric Oxide and Hydrogen Sulfide Regulation of Ischemic Vascular Remodeling.

    Science.gov (United States)

    Yuan, Shuai; Kevil, Christopher G

    2016-02-01

    Blockage or restriction of blood flow through conduit arteries results in tissue ischemia downstream of the disturbed area. Local tissues can adapt to this challenge by stimulating vascular remodeling through angiogenesis and arteriogenesis thereby restoring blood perfusion and removal of wastes. Multiple molecular mechanisms of vascular remodeling during ischemia have been identified and extensively studied. However, therapeutic benefits from these findings and insights are limited due to the complexity of various signaling networks and a lack of understanding central metabolic regulators governing these responses. The gasotransmitters NO and H2 S have emerged as master regulators that influence multiple molecular targets necessary for ischemic vascular remodeling. In this review, we discuss how NO and H2 S are individually regulated under ischemia, what their roles are in angiogenesis and arteriogenesis, and how their interaction controls ischemic vascular remodeling. PMID:26381654

  7. Global gene expression profiling displays a network of dysregulated genes in non-atherosclerotic arterial tissue from patients with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Skov Vibe

    2012-02-01

    Full Text Available Abstract Background Generalized arterial alterations, such as endothelial dysfunction, medial matrix accumulations, and calcifications are associated with type 2 diabetes (T2D. These changes may render the vessel wall more susceptible to injury; however, the molecular characteristics of such diffuse pre-atherosclerotic changes in diabetes are only superficially known. Methods To identify the molecular alterations of the generalized arterial disease in T2D, DNA microarrays were applied to examine gene expression changes in normal-appearing, non-atherosclerotic arterial tissue from 10 diabetic and 11 age-matched non-diabetic men scheduled for a coronary by-pass operation. Gene expression changes were integrated with GO-Elite, GSEA, and Cytoscape to identify significant biological pathways and networks. Results Global pathway analysis revealed differential expression of gene-sets representing matrix metabolism, triglyceride synthesis, inflammation, insulin signaling, and apoptosis. The network analysis showed a significant cluster of dysregulated genes coding for both intra- and extra-cellular proteins associated with vascular cell functions together with genes related to insulin signaling and matrix remodeling. Conclusions Our results identify pathways and networks involved in the diffuse vasculopathy present in non-atherosclerotic arterial tissue in patients with T2D and confirmed previously observed mRNA-alterations. These abnormalities may play a role for the arterial response to injury and putatively for the accelerated atherogenesis among patients with diabetes.

  8. Role of arginase in vessel wall remodeling

    Directory of Open Access Journals (Sweden)

    William eDurante

    2013-05-01

    Full Text Available Arginase metabolizes the semi-essential amino acid L-arginine to L-ornithine and urea. There are two distinct isoforms of arginase, arginase I and II, which are encoded by separate genes and display differences in tissue distribution, subcellular localization, and molecular regulation. Blood vessels express both arginase I and II but their distribution appears to be cell-, vessel-, and species-specific. Both isoforms of arginase are induced by numerous pathologic stimuli and contribute to vascular cell dysfunction and vessel wall remodeling in several diseases. Clinical and experimental studies have documented increases in the expression and/or activity of arginase I or II in blood vessels following arterial injury and in pulmonary and arterial hypertension, aging, and atherosclerosis. Significantly, pharmacological inhibition or genetic ablation of arginase in animals ameliorates abnormalities in vascular cells and normalizes blood vessel architecture and function in all of these pathological states. The detrimental effect of arginase in vascular remodeling is attributable to its ability to stimulate vascular smooth muscle cell and endothelial cell proliferation, and collagen deposition by promoting the synthesis of polyamines and L-proline, respectively. In addition, arginase adversely impacts arterial remodeling by directing macrophages towards an inflammatory phenotype. Moreover, the proliferative, fibrotic, and inflammatory actions of arginase in the vasculature are further amplified by its capacity to inhibit nitric oxide synthesis by competing with nitric oxide synthase for substrate, L-arginine. Pharmacologic or molecular approaches targeting specific isoforms of arginase represent a promising strategy in treating obstructive fibroproliferative vascular disease.

  9. Insulin Injection

    Science.gov (United States)

    ... placed in dosing pens. Be sure you know what type of container your insulin comes in and what other supplies, such as needles, syringes, or pens, ... name and letter on your insulin are exactly what your doctor prescribed.If ... a syringe marked for that type of insulin. Always use the same brand and ...

  10. Oral Insulin

    OpenAIRE

    Kalra Sanjay; Kalra Bharti; Agrawal Navneet

    2010-01-01

    Abstract Oral insulin is an exciting area of research and development in the field of diabetology. This brief review covers the various approaches used in the development of oral insulin, and highlights some of the recent data related to novel oral insulin preparation.

  11. Variations in atherosclerosis and remodeling patterns in aorta and carotids

    Directory of Open Access Journals (Sweden)

    Fuster Valentin

    2010-03-01

    Full Text Available Abstract Background Atherosclerosis is a progressive disease that causes vascular remodeling that can be positive or negative. The evolution of arterial wall thickening and changes in lumen size under current "standard of care" in different arterial beds is unclear. The purpose of this study was to examine arterial remodeling and progression/regression of atherosclerosis in aorta and carotid arteries of individuals at risk for atherosclerosis normalized over a 1-year period. Methods In this study, 28 patients underwent at least 2 black-blood in vivo cardiovascular magnetic resonance (CMR scans of aorta and carotids over a one-year period (Mean 17.8 ± 7.5 months. Clinical risk profiles for atherosclerosis and medications were documented and patients were followed by their referring physicians under current "standard of care" guidelines. Carotid and aortic wall lumen areas were matched across the time-points from cross-sectional images. Results The wall area increased by 8.67%, 10.64%, and 13.24% per year (carotid artery, thoracic aorta and abdominal aorta respectively, p Conclusions Results of this study of multiple vascular beds indicated that different vascular locations exhibited varying progression of atherosclerosis and remodeling as monitored by CMR.

  12. Compensatory Effect between Aortic Stiffening and Remodelling during Ageing.

    Directory of Open Access Journals (Sweden)

    Andrea Guala

    Full Text Available The arterial tree exhibits a complex spatio-temporal wave pattern, whose healthy behaviour depends on a subtle balance between mechanical and geometrical properties. Several clinical studies demonstrated that such a balance progressively breaks down during ageing, when the aorta stiffens and remodels by increasing its diameter. These two degenerative processes however, have different impacts on the arterial wave pattern. They both tend to compensate for each other, thus reducing the detrimental effect they would have had if they had arisen individually. This remarkable compensatory mechanism is investigated by a validated multi-scale model, with the aim to elucidate how aortic stiffening and remodelling quantitatively impact the complex interplay between forward and reflected backward waves in the arterial network. We focus on the aorta and on the pressure at the ventricular-aortic interface, which epidemiological studies demonstrate to play a key role in cardiovascular diseases.

  13. Mechanical stretch augments insulin-induced vascular smooth muscle cell proliferation by insulin-like growth factor-1 receptor

    International Nuclear Information System (INIS)

    Insulin resistance and hypertension have been implicated in the pathogenesis of cardiovascular disease; however, little is known about the roles of insulin and mechanical force in vascular smooth muscle cell (VSMC) remodeling. We investigated the contribution of mechanical stretch to insulin-induced VSMC proliferation. Thymidine incorporation was stimulated by insulin in stretched VSMCs, but not in un-stretched VSMCs. Insulin increased 2-deoxy-glucose incorporation in both stretched and un-stretched VSMCs. Mechanical stretch augmented insulin-induced extracellular signal-regulated kinase (ERK) and Akt phosphorylation. Inhibitors of epidermal growth factor (EGF) receptor tyrosine kinase and Src attenuated insulin-induced ERK and Akt phosphorylation, as well as thymidine incorporation, whereas 2-deoxy-glucose incorporation was not affected by these inhibitors. Moreover, stretch augmented insulin-like growth factor (IGF)-1 receptor expression, although it did not alter the expression of insulin receptor and insulin receptor substrate-1. Insulin-induced ERK and Akt activation, and thymidine incorporation were inhibited by siRNA for the IGF-1 receptor. Mechanical stretch augments insulin-induced VSMC proliferation via upregulation of IGF-1 receptor, and downstream Src/EGF receptor-mediated ERK and Akt activation. Similar to in vitro experiment, IGF-1 receptor expression was also augmented in hypertensive rats. These results provide a basis for clarifying the molecular mechanisms of vascular remodeling in hypertensive patients with hyperinsulinemia. -- Highlights: → Mechanical stretch augments insulin-induced VSMC proliferation via IGF-1 receptor. → Src/EGFR-mediated ERK and Akt phosphorylation are augmented in stretched VSMCs. → Similar to in vitro experiment, IGF-1 receptor is increased in hypertensive rats. → Results provide possible mechanisms of vascular remodeling in hypertension with DM.

  14. Mechanical stretch augments insulin-induced vascular smooth muscle cell proliferation by insulin-like growth factor-1 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Gang [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang (China); Hitomi, Hirofumi, E-mail: hitomi@kms.ac.jp [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Hosomi, Naohisa [Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Kagawa (Japan); Lei, Bai; Nakano, Daisuke [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Deguchi, Kazushi; Mori, Hirohito; Masaki, Tsutomu [Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Ma, Hong [Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang (China); Griendling, Kathy K. [Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA (United States); Nishiyama, Akira [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan)

    2011-10-15

    Insulin resistance and hypertension have been implicated in the pathogenesis of cardiovascular disease; however, little is known about the roles of insulin and mechanical force in vascular smooth muscle cell (VSMC) remodeling. We investigated the contribution of mechanical stretch to insulin-induced VSMC proliferation. Thymidine incorporation was stimulated by insulin in stretched VSMCs, but not in un-stretched VSMCs. Insulin increased 2-deoxy-glucose incorporation in both stretched and un-stretched VSMCs. Mechanical stretch augmented insulin-induced extracellular signal-regulated kinase (ERK) and Akt phosphorylation. Inhibitors of epidermal growth factor (EGF) receptor tyrosine kinase and Src attenuated insulin-induced ERK and Akt phosphorylation, as well as thymidine incorporation, whereas 2-deoxy-glucose incorporation was not affected by these inhibitors. Moreover, stretch augmented insulin-like growth factor (IGF)-1 receptor expression, although it did not alter the expression of insulin receptor and insulin receptor substrate-1. Insulin-induced ERK and Akt activation, and thymidine incorporation were inhibited by siRNA for the IGF-1 receptor. Mechanical stretch augments insulin-induced VSMC proliferation via upregulation of IGF-1 receptor, and downstream Src/EGF receptor-mediated ERK and Akt activation. Similar to in vitro experiment, IGF-1 receptor expression was also augmented in hypertensive rats. These results provide a basis for clarifying the molecular mechanisms of vascular remodeling in hypertensive patients with hyperinsulinemia. -- Highlights: {yields} Mechanical stretch augments insulin-induced VSMC proliferation via IGF-1 receptor. {yields} Src/EGFR-mediated ERK and Akt phosphorylation are augmented in stretched VSMCs. {yields} Similar to in vitro experiment, IGF-1 receptor is increased in hypertensive rats. {yields} Results provide possible mechanisms of vascular remodeling in hypertension with DM.

  15. Immunoregulation of bone remodelling

    Science.gov (United States)

    Singh, Ajai; Mehdi, Abbass A; Srivastava, Rajeshwer N; Verma, Nar Singh

    2012-01-01

    Remodeling, a continuous physiological process maintains the strength of the bones, which maintains a delicate balance between bone formation and resorption process. This review gives an insight to the complex interaction and correlation between the bone remodeling and the corresponding changes in host immunological environment and also summarises the most recent developments occuring in the understanding of this complex field. T cells, both directly and indirectly increase the expression of receptor activator of nuclear factor kB ligand (RANKL); a vital step in the activation of osteoclasts, thus positively regulates the osteoclastogenesis. Though various cytokines, chemikines, transcription factors and co-stimulatory molecules are shared by both skeletal and immune systems, but researches are being conducted to establish and analyse their role and / or control on this complex but vital process. The understanding of this part of research may open new horizons in the management of inflammatory and autoimmune diseases, resulting into bone loss and that of osteoporosis also. PMID:22837895

  16. Disruption of TGF-β signaling in smooth muscle cell prevents flow-induced vascular remodeling

    International Nuclear Information System (INIS)

    Highlights: • TGF-β signaling in SMC contributes to the flow-induced vascular remodeling. • Disruption of TGF-β signaling in SMC can prevent this process. • Targeting SM-specific Tgfbr2 could be a novel therapeutic strategy for vascular remodeling. - Abstract: Transforming growth factor-β (TGF-β) signaling has been prominently implicated in the pathogenesis of vascular remodeling, especially the initiation and progression of flow-induced vascular remodeling. Smooth muscle cells (SMCs) are the principal resident cells in arterial wall and are critical for arterial remodeling. However, the role of TGF-β signaling in SMC for flow-induced vascular remodeling remains unknown. Therefore, the goal of our study was to determine the effect of TGF-β pathway in SMC for vascular remodeling, by using a genetical smooth muscle-specific (SM-specific) TGF-β type II receptor (Tgfbr2) deletion mice model. Mice deficient in the expression of Tgfbr2 (MyhCre.Tgfbr2f/f) and their corresponding wild-type background mice (MyhCre.Tgfbr2WT/WT) underwent partial ligation of left common carotid artery for 1, 2, or 4 weeks. Then the carotid arteries were harvested and indicated that the disruption of Tgfbr2 in SMC provided prominent inhibition of vascular remodeling. And the thickening of carotid media, proliferation of SMC, infiltration of macrophage, and expression of matrix metalloproteinase (MMP) were all significantly attenuated in Tgfbr2 disruption mice. Our study demonstrated, for the first time, that the TGF-β signaling in SMC plays an essential role in flow-induced vascular remodeling and disruption can prevent this process

  17. Disruption of TGF-β signaling in smooth muscle cell prevents flow-induced vascular remodeling

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Fu [Department of Vascular Surgery, Peking University People’s Hospital, Beijing (China); Chambon, Pierre [Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS UMR7104, INSERM U596, ULP, Collége de France) and Institut Clinique de la Souris, ILLKIRCH, Strasbourg (France); Tellides, George [Department of Surgery, Interdepartmental Program in Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, CT (United States); Kong, Wei [Department of Physiology and Pathophysiology, Basic Medical College of Peking University, Beijing (China); Zhang, Xiaoming, E-mail: rmygxgwk@163.com [Department of Vascular Surgery, Peking University People’s Hospital, Beijing (China); Li, Wei [Department of Vascular Surgery, Peking University People’s Hospital, Beijing (China)

    2014-11-07

    Highlights: • TGF-β signaling in SMC contributes to the flow-induced vascular remodeling. • Disruption of TGF-β signaling in SMC can prevent this process. • Targeting SM-specific Tgfbr2 could be a novel therapeutic strategy for vascular remodeling. - Abstract: Transforming growth factor-β (TGF-β) signaling has been prominently implicated in the pathogenesis of vascular remodeling, especially the initiation and progression of flow-induced vascular remodeling. Smooth muscle cells (SMCs) are the principal resident cells in arterial wall and are critical for arterial remodeling. However, the role of TGF-β signaling in SMC for flow-induced vascular remodeling remains unknown. Therefore, the goal of our study was to determine the effect of TGF-β pathway in SMC for vascular remodeling, by using a genetical smooth muscle-specific (SM-specific) TGF-β type II receptor (Tgfbr2) deletion mice model. Mice deficient in the expression of Tgfbr2 (MyhCre.Tgfbr2{sup f/f}) and their corresponding wild-type background mice (MyhCre.Tgfbr2{sup WT/WT}) underwent partial ligation of left common carotid artery for 1, 2, or 4 weeks. Then the carotid arteries were harvested and indicated that the disruption of Tgfbr2 in SMC provided prominent inhibition of vascular remodeling. And the thickening of carotid media, proliferation of SMC, infiltration of macrophage, and expression of matrix metalloproteinase (MMP) were all significantly attenuated in Tgfbr2 disruption mice. Our study demonstrated, for the first time, that the TGF-β signaling in SMC plays an essential role in flow-induced vascular remodeling and disruption can prevent this process.

  18. Autonomic disbalance their relationship with the cardiovascular hiperreactivity, the resistance to the insulin and the high blood pressure. Desequilibrio autonómico simpático su relación con la hiperreactividad cardiovascular, la resistencia a la insulina y a la hipertensión arterial

    Directory of Open Access Journals (Sweden)

    Yosvel Curbelo Pérez

    Full Text Available During many years has been debated the paper of the Autonomous Nervous System in the development of the arterial hypertension, in passing it constitutes one of the important theories that physiologists. Recently some authors have involved the activity of that system with the resistance to the insulin and with other important aspects that influence in the appearance of arterial hypertension. The objective of this work is to contribute new theoretical elements that link the changes of the activity of the Autonomous Nervous System with the presence of cardiovascular hipereactivity and sustained arterial hypertension.

    Durante muchos años se ha debatido sobre el papel del Sistema Nervioso Autónomo en el desarrollo de la hipertensión arterial, de paso constituye una de las teorías importantes que plantean fisiólogos y estudiosos. Más recientemente algunos autores han involucrado la actividad de ese sistema con la resistencia a la insulina y con otros aspectos importantes que influyen en la aparición de hipertensión arterial. El objetivo de este trabajo es aportar nuevos elementos teóricos que vinculan los cambios de la actividad del Sistema Nervioso Autónomo con la presencia de hiperreactividad cardiovascular e hipertensión arterial sostenida.

  19. Arterial Catheterization

    Science.gov (United States)

    ... version AMERICAN THORACIC SOCIETY Patient Information Series Arterial Catheterization An arterial catheter is a thin, hollow tube ... PHYSICIANS: AND COPY Why Do I Need Arterial Catheterization? Common reasons an arterial catheterization is done include: ■ ...

  20. Сharacteristics of flexible elastic properties of the carotid arteries in women with arterial hypertension

    Directory of Open Access Journals (Sweden)

    Коval О.A.

    2013-10-01

    Full Text Available The article presents the results of study of the features of the carotid wall structure using ultrasound scanning with differential measurement of intima and media thickness, as well as characteristics of arterial elasticity in women with hypertension without comorbidities. It is shown that in women with hypertension vascular remodeling occurs mainly in the form of thickening of the intima-media due to increase in the media layer and is associated with remodeling of the left heart. Carotid remodeling in women with hypertension is associated with worsening of vascular elasticity - increased vascular stiffness and decreased distension, wherein correlation analysis has shown that mentioned parameters are mostly associated with thickening of the medial layer of the artery wall and increase of internal diameter of the artery, as well as with increase in left ventricular mass. Ultrasound method of estimating elastic characteristics of arterial vessels is informative, relatively inexpensive and safe.

  1. [THE EFFECTIVENESS OF THE CORRECTION OF ENDOTHELIAL DYSFUNCTION AND REMODELING OF THE BRACHIAL ARTERY WITH CONCENTRIC AND ECCENTRIC LEFT VENTRICULAR HYPERTROPHY IN PATIENTS WITH UNSTABLE ANGINA WITH COMORBID HYPERTENSION].

    Science.gov (United States)

    Denesiuk, E V

    2015-01-01

    The study involved patients with unstable angina (UA), comorbid hypertension (AH), myocardial infarction in 55.5% of cases. Systolic blood pressure was (163.2 ± 1.5) mm Hg. Art., diastolic blood pressure--(101.10 ± 0.67) mm Hg. Art., pulse pressure--(61.1 ± 17.0) mm Hg. Art. Examined patients underwent clinical studies, ECG in 12 conventional leads, echocardiography in M and B modes, Doppler ultrasonography of the brachial artery. To correct the detected change using standard combined therapy: perindopril 5-10 mg/day, bisoprolol--5-10 mg/day, atorvastatin--20 mg/day, acetylsalicylic acid--75-100 mg/day. Monitoring the treatment was carried out at 3; 6 and 12 months. Standard one-year comprehensive treatment of patients with UA with comorbid AH resulted in significant improvement of effective endothelial dysfunction in concentric and eccentric left ventricular hypertrophy in 3; 6 and 12 months, however, regression of hypertrophy brachial artery advancing much less mainly in concentric left ventricular hypertrophy. PMID:27089719

  2. Vascular remodeling as compensatory changes in different degrees of varicocele

    Directory of Open Access Journals (Sweden)

    E. S. Severgina

    2013-01-01

    Full Text Available We investigated biosises obtained from children with different varicocele stages and showed the possibility of remodeling development in different type vein walls. Most typical changes were found in the third type vein walls – multiple rolls, composed of muscular and collagen bundles; in the larger first and second type veins markers of arterialization were seen. These processes are the manifestations of adaptive response, which is connected with elevated venous pressure; they can improve testicular hemodynamic.

  3. Vascular remodeling as compensatory changes in different degrees of varicocele

    Directory of Open Access Journals (Sweden)

    E. S. Severgina

    2014-11-01

    Full Text Available We investigated biosises obtained from children with different varicocele stages and showed the possibility of remodeling development in different type vein walls. Most typical changes were found in the third type vein walls – multiple rolls, composed of muscular and collagen bundles; in the larger first and second type veins markers of arterialization were seen. These processes are the manifestations of adaptive response, which is connected with elevated venous pressure; they can improve testicular hemodynamic.

  4. Die Rolle der Mastzellen im vaskulären Remodelling bei Lungenhochdruck infolge von Linksherzerkrankung

    OpenAIRE

    Hoffmann, Julia

    2012-01-01

    Analyses of functional genomics in PH and associated vascular Remodelling processes identified mast cells as potential targets for novel therapeutic strategies. Mast cells have been implicated in the pathophysiology of lung cancer and asthma but their role in vascular Remodelling and PH remains unclear. Here, we tested the role of mast cells in experimental models of PH owing to left heart disease and pulmonary arterial hypertension using two different approaches. PH with left heart diseas...

  5. mTOR and vascular remodeling in lung diseases: current challenges and therapeutic prospects

    OpenAIRE

    Goncharova, Elena A

    2013-01-01

    Mammalian target of rapamycin (mTOR) is a major regulator of cellular metabolism, proliferation, and survival that is implicated in various proliferative and metabolic diseases, including obesity, type 2 diabetes, hamartoma syndromes, and cancer. Emerging evidence suggests a potential critical role of mTOR signaling in pulmonary vascular remodeling. Remodeling of small pulmonary arteries due to increased proliferation, resistance to apoptosis, and altered metabolism of cells forming the pulmo...

  6. Myocardial Infarction in a Young Female with Palindromic Rheumatism: A Consequence of Negative Remodeling

    Directory of Open Access Journals (Sweden)

    Timothy R. Larsen

    2012-01-01

    Full Text Available Palindromic rheumatism is a rare disease associated with systemic inflammation. Negative or constrictive coronary artery remodeling is typically not seen until the 7th or 8th decade of life. We report a case of a young female with palindromic rheumatism who suffered a non-ST segment elevation myocardial infarction secondary to a flow-limiting lesion that demonstrated negative remodeling by intravascular ultrasound (IVUS.

  7. Newer insulin analogues and inhaled insulin

    OpenAIRE

    Girish C; Manikandan S; Jayanthi M

    2006-01-01

    Diabetes is a metabolic disease with high prevalence worldwide. Exogenous insulin is used in the management of this condition. The development of human insulin has provided tighter control of glycaemia in diabetic patients. Insulin analogues like insulin lispro and aspart were developed to closely match its profile with physiological secretion. The newer additions to this armamentarium are insulin glulisine, insulin detemir and albulin.Insulin glulisine is a short acting analogue with a rapid...

  8. Insulin Injection

    Science.gov (United States)

    ... not use any type of insulin after the expiration date printed on the bottle has passed.Some ... or itching over the whole body shortness of breath wheezing dizziness blurred vision fast heartbeat sweating difficulty ...

  9. No-Regrets Remodeling, 2nd Edition

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-12-01

    No-Regrets Remodeling, sponsored by Oak Ridge National Laboratory, is an informative publication that walks homeowners and/or remodelers through various home remodeling projects. In addition to remodeling information, the publication provides instruction on how to incorporate energy efficiency into the remodeling process. The goal of the publication is to improve homeowner satisfaction after completing a remodeling project and to provide the homeowner with a home that saves energy and is comfortable and healthy.

  10. PARP inhibition and postinfarction myocardial remodeling.

    Science.gov (United States)

    Halmosi, Robert; Deres, Laszlo; Gal, Roland; Eros, Krisztian; Sumegi, Balazs; Toth, Kalman

    2016-08-01

    Coronary artery disease accounts for the greatest proportion of cardiovascular diseases therefore it is the major cause of death worldwide. Its therapeutic importance is indicated by still high mortality of myocardial infarction, which is one of the most severe forms of CVDs. Moreover, the risk of developing heart failure is very high among survivors. Heart failure is accompanied by high morbidity and mortality rate, therefore this topic is in the focus of researchers' interest. After a myocardial infarct, at first ventricular hypertrophy develops as a compensatory mechanism to decrease wall stress but finally leads to left ventricular dilation. This phenomenon is termed as myocardial remodeling. The main characteristics of underlying mechanisms involve cardiomyocyte growth, vessel changes and increased collagen production, in all of which several mechanical stress induced neurohumoral agents, oxidative stress and signal transduction pathways are involved. The long term activation of these processes ultimately leads to left ventricular dilation and heart failure with decreased systolic function. Oxidative stress causes DNA breaks producing the activation of nuclear poly(ADP-ribose) polymerase-1 (PARP-1) enzyme that leads to energy depletion and unfavorable modulation of different kinase cascades (Akt-1/GSK-3β, MAPKs, various PKC isoforms) and thus it promotes the development of heart failure. Therefore inhibition of PARP enzyme could offer a promising new therapeutical approach to prevent the onset of heart failure among postinfarction patients. The purpose of this review is to give a comprehensive summary about the most significant experimental results and mechanisms in postinfarction remodeling. PMID:27392900

  11. Idiopathic Pulmonary Arterial Hypertension: An Avian Model for Plexogenic Arteriopathy and Serotonergic Vasoconstriction

    OpenAIRE

    Wideman, Robert F.; Hamal, Krishna R.

    2011-01-01

    Idiopathic pulmonary arterial hypertension (IPAH) is a disease of unknown cause that is characterized by elevated pulmonary arterial pressure and pulmonary vascular resistance attributable to vasoconstriction and vascular remodeling of small pulmonary arteries. Vascular remodeling includes hypertrophy and hyperplasia of smooth muscle (medial hypertrophy) accompanied in up to 80% of the cases by the formation of occlusive plexiform lesions (plexogenic arteriopathy). Patients tend to be unrespo...

  12. Insulin resistance and exercise tolerance in heart failure patients

    DEFF Research Database (Denmark)

    Snoer, Martin; Monk-Hansen, Tea; Olsen, Rasmus Huan;

    2012-01-01

    Insulin resistance has been linked to exercise intolerance in heart failure patients. The aim of this study was to assess the potential role of coronary flow reserve (CFR), endothelial function and arterial stiffness in explaining this linkage.......Insulin resistance has been linked to exercise intolerance in heart failure patients. The aim of this study was to assess the potential role of coronary flow reserve (CFR), endothelial function and arterial stiffness in explaining this linkage....

  13. Сharacteristics of flexible elastic properties of the carotid arteries in women with arterial hypertension

    OpenAIRE

    Коval О.A.; Zubko I.M.

    2013-01-01

    The article presents the results of study of the features of the carotid wall structure using ultrasound scanning with differential measurement of intima and media thickness, as well as characteristics of arterial elasticity in women with hypertension without comorbidities. It is shown that in women with hypertension vascular remodeling occurs mainly in the form of thickening of the intima-media due to increase in the media layer and is associated with remodeling of the left heart. Carotid re...

  14. A Novel Algorithm to Quantify Coronary Remodeling Using Inferred Normal Dimensions

    Directory of Open Access Journals (Sweden)

    Breno A. A. Falcão

    2015-01-01

    Full Text Available Background:Vascular remodeling, the dynamic dimensional change in face of stress, can assume different directions as well as magnitudes in atherosclerotic disease. Classical measurements rely on reference to segments at a distance, risking inappropriate comparison between dislike vessel portions.Objective:to explore a new method for quantifying vessel remodeling, based on the comparison between a given target segment and its inferred normal dimensions.Methods:Geometric parameters and plaque composition were determined in 67 patients using three-vessel intravascular ultrasound with virtual histology (IVUS-VH. Coronary vessel remodeling at cross-section (n = 27.639 and lesion (n = 618 levels was assessed using classical metrics and a novel analytic algorithm based on the fractional vessel remodeling index (FVRI, which quantifies the total change in arterial wall dimensions related to the estimated normal dimension of the vessel. A prediction model was built to estimate the normal dimension of the vessel for calculation of FVRI.Results:According to the new algorithm, “Ectatic” remodeling pattern was least common, “Complete compensatory” remodeling was present in approximately half of the instances, and “Negative” and “Incomplete compensatory” remodeling types were detected in the remaining. Compared to a traditional diagnostic scheme, FVRI-based classification seemed to better discriminate plaque composition by IVUS-VH.Conclusion:Quantitative assessment of coronary remodeling using target segment dimensions offers a promising approach to evaluate the vessel response to plaque growth/regression.

  15. Cerebral Blood Flow Links Insulin Resistance and Baroreflex Sensitivity

    OpenAIRE

    Ryan, John P.; Sheu, Lei K.; Verstynen, Timothy D.; Onyewuenyi, Ikechukwu C.; Gianaros, Peter J.

    2013-01-01

    Insulin resistance confers risk for diabetes mellitus and associates with a reduced capacity of the arterial baroreflex to regulate blood pressure. Importantly, several brain regions that comprise the central autonomic network, which controls the baroreflex, are also sensitive to the neuromodulatory effects of insulin. However, it is unknown whether peripheral insulin resistance relates to activity within central autonomic network regions, which may in turn relate to reduced baroreflex regula...

  16. Value of Angiotensin-Converting Enzyme and Monoxide Nitrogen in Pathogenesis of Myocardium Remodeling Depending on Genes' Polymorphism of Асе (I/D and eNOS (894T>G in Patients with Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    Sydorchuk L.P.

    2013-03-01

    Full Text Available Introduction: Humans genes mutations in altered social conditions through interaction with environmental factors and harmful habits become an individual risk factor. Objectives: To evaluate Angiotensin-Converting Enzyme (ACE and nitrogen monoxide metabolites (NO/NO2-/NO3- blood levels depending on I/D polymorphism of ACE gene (dbSNP id:rs4646994, 894T>G of Endothelial Nitric Oxide Synthase (eNOS, dbSNP id:rs1799983 in pathogenesis of left ventricular hypertrophy (LVH in patients with Essential Arterial Hypertension (EAH. Methods: 120 screened patients with EAH I-III stages (48.3% – women, 51.7% – men, average age 52.9±9.24 years and 40 healthy persons participated in prospective study. Alleles of polymorphic locus were studied by PCR method. Serum ACE level was detected by ELISA. Plasma NO metabolites levels were determined by colorimetric method. Structural myocardium changes – by EchoCG, ECG. Results analyzed according to the European guidelines ESC/ESH (2009.Results: D-allele presence (ACE associated with high risk of LVH geometric patterns and higher level of ACE. Presence of TT-genotype of eNOS gene (ID/TT-haplotype associated with lower levels of NO metabolites by 14.5% (р<0.05. Homozygous D-allele carriers (regardless of genotypes combination of eNOS gene – DD/TG, DD/GG haplotypes have ACE concentration increased by 18.1% and 17.5%, accordingly (р<0.05. The absence of mutations in haplotypes (II/GG is a protective factor against LVH (OR=0.13, p=0.047, with the lowest level of ACE, followed by higher concentration of NO metabolites (p<0.05. The combination of D+T allele in haplotypes (ID/TG, DD/TG increases the relative risk of LVH and EAH II and III in 1.19-2.25 times (OR=4.75-13.5, p≤0.021-0.001, which is confirmed by severity of clinical course, and increased ACE serum level (DD/TG carriers.Conclusion: Risk groups for eccentric or concentric LVH models are D-allele carriers (ACE gene with highest ACE level and T-allele of e

  17. Arterial stick

    Science.gov (United States)

    ... the main arteries in the forearm (radial and ulnar arteries). The procedure is done as follows: The ... Arteries also have thicker walls and have more nerves. When the needle is inserted, there may be ...

  18. Transcriptome Analysis and Gene Identification in the Pulmonary Artery of Broilers with Ascites Syndrome

    Science.gov (United States)

    Xiao, Qingyang; Guo, Xiaoquan; Zhuang, Yu; Zhang, Caiying; Wang, Tiancheng; Lin, Huayuan; Song, Yalu; Hu, Guoliang; Liu, Ping

    2016-01-01

    Background Pulmonary arterial hypertension, also known as Ascites syndrome (AS), remains a clinically challenging disease with a large impact on both humans and broiler chickens. Pulmonary arterial remodeling presents a key step in the development of AS. The precise molecular mechanism of pulmonary artery remodeling regulating AS progression remains unclear. Methodology/Principal Findings We obtained pulmonary arteries from two positive AS and two normal broilers for RNA sequencing (RNA-seq) analysis and pathological observation. RNA-seq analysis revealed a total of 895 significantly differentially expressed genes (DEGs) with 437 up-regulated and 458 down-regulated genes, which were significantly enriched to 12 GO (Gene Ontology) terms and 4 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways (Padj<0.05) regulating pulmonary artery remodeling and consequently occurrence of AS. These GO terms and pathways include ribosome, Jak-STAT and NOD-like receptor signaling pathways which regulate pulmonary artery remodeling through vascular smooth cell proliferation, inflammation and vascular smooth cell proliferation together. Some notable DEGs within these pathways included downregulation of genes like RPL 5, 7, 8, 9, 14; upregulation of genes such as IL-6, K60, STAT3, STAT5 Pim1 and SOCS3; IKKα, IkB, P38, five cytokines IL-6, IL8, IL-1β, IL-18, and MIP-1β. Six important regulators of pulmonary artery vascular remodeling and construction like CYP1B1, ALDH7A1, MYLK, CAMK4, BMP7 and INOS were upregulated in the pulmonary artery of AS broilers. The pathology results showed that the pulmonary artery had remodeled and become thicker in the disease group. Conclusions/Significance Our present data suggested some specific components of the complex molecular circuitry regulating pulmonary arterial remodeling underlying AS progression in broilers. We revealed some valuable candidate genes and pathways that involved in pulmonary artery remodeling further contributing to the AS

  19. Glucose-stimulated Cdc42 Signaling Is Essential for the Second Phase of Insulin Secretion*

    OpenAIRE

    Wang, Zhanxiang; Oh, Eunjin; Thurmond, Debbie C.

    2007-01-01

    The small Rho family GTPases Cdc42 and Rac1 have each been shown to function in insulin exocytosis and are presumed to function in actin remodeling and insulin granule mobilization. However, whether either GTPase is required for the mobilization phase of insulin release (second phase) and are linked in a common signaling pathway has remained unknown. Here we demonstrate that small interfering RNA-mediated depletion of Cdc42 from isolated islets results in the selective loss of second-phase in...

  20. Effect of hemin on the lung development and pulmonary arterial structural remodeling in congenital diaphragmatic hernia: experiment with rats%血晶素对先天性膈疝大鼠模型胎仔肺发育肺血管重构的影响

    Institute of Scientific and Technical Information of China (English)

    王元祥; 刘文英; 林涵; 徐畅; 唐耘熳; 位永娟; 覃道锐

    2008-01-01

    Objective To assay the effects of prenatal hemin therapy on pulmonary hypoplasia (PH)and pulmonary arterial structural remodeling in congenital diaphragmatic hernia(CDH). Methods Six pregnant female SD rats were randomly divided into 3 equal groups: control group, undergoing gastric perfusion of olive oil once on day 9. 5 and intraperitoneal injection of normal saline on days 11-14: CDH group, undergoing gastric perfusion of nitrofen 125 mg once on day 9. 5 and intraperitoneal injection of normal saline on days 11-14;and hemin group, undergoing gastric perfusion of nitrofen 125 mg once on caesarean section was performed to take out the fetuses to undergo histological examination and image analysis. Results CDH were detected in 28 of the 44(63. 6%)fetuses from the 2 groups receiving nitrofen. The lungs of all CDH group fetuses were hypoplastic, and the fetuses of the hemin group showed improved lung development. The right lung/body weight ratio and pulmonary alveolar area ratio(PAA%)of the hemin group were(16. 6±1. 0)mg/g and(45±6)% respectively, both significantly higher than those of the CDH group[(14. 6±1. 7)mg/g and(28±6)% respectively, P=0. 03 and P<0. 01]. The alveolar septum area ratio(ASA%)of the hemin group was(44±6)%, significantly lower than that of the CDH group[(64±8)%, P<0. 01]. The media thickness percentages(MT%)of pre-acinar artery (PAPA)and intra-acinar artery(IAPA)of the fetuses of the hemin group were(21. 2±2. 2)% and (18. 2±2. 1)% respectively, both significantly lower than those of the CDH group[(24. 3±4. 0)% and (21. 9±3. 9)% respectively, both P<0. 05], which were significantly higher than those of the control group[(20. 0±2. 4)% and(17. 2±2. 3)% respectively, both P<0. 01]. The component ratio of nonmuscularized artery(NMA)in the IAPA level of the hemin group was(78. 2±3. 0)%, significantly higher than that of the CDH group[(72. 8±3. 2)%, P=0. 001]. Conclusion PH and pulmonary arterial structural remodeling are present

  1. Collagen turnover in arterial disease

    OpenAIRE

    Sluijter, J.P.G.

    2004-01-01

    Increased atherosclerotic plaque formation can lead to lumen reduction and finally to lumen obstruction. Percutaneous transluminal angioplasty (PTA) or balloon angioplasty (dilation) are approaches generally used to treat coronary, but also peripheral atherosclerotic disease. Their goal is to restore the blood supply. The repair process or restructuring of the artery after balloon angioplasty comprises two major features, neointimal formation and geometrical remodeling, and results in a decre...

  2. Hyperhomocysteinemia promotes vascular remodeling in vein graph in mice.

    Science.gov (United States)

    Tan, Hongmei; Shi, Chengwei; Jiang, Xiaohua; Lavelle, Muriel; Yu, Caijia; Yang, Xiaofeng; Wang, Hong

    2014-01-01

    This study investigated the role and mechanism of Hyperhomocysteinemia (HHcy) on vascular remodeling in mice. We assessed the effect of HHcy on vascular remodeling using a carotid arterial vein patch model in mice with the gene deletion of cystathionine-beta-synthase (Cbs). Vein grafts were harvested 4 weeks after surgery. Cross sections were analyzed using Verhoeff-van Gieson staining, Masson`s Trichrome staining, and immunostaining for morphological analysis and protein level assessment. The effect of Hcy on collagen secretion was examined in cultured rat aortic smooth muscle cells (RASMC). We found that Cbs-/- mice with severe HHcy exhibited thicker neointima and a higher percentage of luminal narrowing in vein grafts. In addition, severe HHcy increased elastin and collagen deposition in the neointima. Further, severe HHcy increases CD45 positive cells and proliferative cells in vein grafts. Finally, Hcy increases collagen secretion in RASMC. These results demonstrate that HHcy increases neointima formation, elastin and collagen deposition following a carotid arterial vein patch. The capacity of Hcy to promote vascular fibrosis and inflammation may contribute to the development of vascular remodeling. PMID:24896329

  3. Postprandial Vascular Effects of VIAject Compared With Insulin Lispro and Regular Human Insulin in Patients With Type 2 Diabetes

    Science.gov (United States)

    Forst, Thomas; Pfützner, Andreas; Flacke, Frank; Krasner, Alan; Hohberg, Cloth; Tarakci, Eda; Pichotta, Philip; Forst, Senait; Steiner, Solomon

    2010-01-01

    OBJECTIVE Recent studies suggested an impact of prandial insulin delivery on postprandial regulation of tissue blood flow. This study compared the effect of VIAject with human regular insulin and insulin lispro on postprandial oxidative stress and endothelial function in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Fourteen patients (seven men; aged 61.5 ± 1.8 years; duration of diabetes 6.6 ± 4.6 years; A1C 7.2 ± 0.5% [mean ± SEM]) received a prandial injection of VIAject, human regular insulin, and insulin lispro. At baseline and after a standardized liquid meal test (Ensure Plus), the postprandial increases in asymmetric dimethylarginine (ADMA) and nitrotyrosine levels were investigated. In addition, the postprandial effects on microvascular blood flow, skin oxygenation, and vascular elasticity were measured. RESULTS Treatment with VIAject resulted in a significant reduction in the peak postprandial generation of ADMA compared with human insulin and insulin lispro (VIAject −27.3 ± 22.6, human insulin 97.7 ± 24.4, and insulin lispro 66.9 ± 33.9 nmol/l; P < 0.05, respectively). The postprandial increases in nitrotyrosine levels were significantly less after VIAject than after human regular insulin (VIAject −0.22 ± 0.17 vs. human insulin 0.25 ± 0.15 μg/ml; P < 0.05), whereas nitrotyrosine after insulin lispro was in between (insulin lispro 0.09 ± 0.07 μg/ml; NS). In parallel, earlier and more pronounced increases in microvascular blood flow and skin oxygenation were obtained after VIAject compared with those after human insulin or insulin lispro (P < 0.05, respectively). All insulin formulations resulted in comparable improvements in central arterial elasticity. CONCLUSIONS Treatment with VIAject reduced postprandial oxidative stress and improved endothelial function compared with human regular insulin or insulin lispro. PMID:19808913

  4. Expression of insulin-like growth factor-1 mRNA and protein level of corpora striata in ischemic side at the early stage of middle cerebral artery ischemia/reperfusion in rhesus monkeys

    Institute of Scientific and Technical Information of China (English)

    Huanmin Gao; Rui Zhang; Yunliang Guo

    2006-01-01

    BACKGROUND: Insulin-like growth factor-I(IGF-1), as one of the important members of growth factor family,participants in the regulation of many physiological functions and behaviors, having very strong neuroprotective effect. However, the expression of IGF-1 following cerebral ischemia/reperfusion is still disputed.OBJ ECTIVE: To observe the expression of IGF-1 and protein of corpora striata in ischemic side at the early stage of middle cerebral artery ischemia/reperfusion in rhesus monkey.DESIGN: A completely randomized grouping design, controlled animal experimentSETTING: Institute of Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University.MATERIALS: ① Totally 17 rhesus monkeys , of either gender, aged 4 to 5 years, were enrolled . Seven rhesus monkeys observed with gene chip were randomly divided into 2 groups: sham operation group (n=3)and ischemia/reperfusion group (n=4). Ten rhesus monkeys observed with in situ hybridization and immunohistochemistry method were randomly divided into 2 groups: sham operation group (n=3)and ischemia/reperfusion group (n=7). Rhesus monkeys observed under microscope were divided into 2 groups: sham operation group (n=6) and ischamia/reperfusion group (n=11). ② Materials used in the experiment: cresyl violet (Sigma Company, America); immunohistochemical reagent kit ( Huamei Bio-engineering Company); In situ hybridization reagent kit (Boshide Bio-engineering Co. Ltd, Wuhan); 12 800 dots chip (Boxing Company,Shanghai).METHODS: This experiment was carried out at the Institute of Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University from January 2001 to December 2003. ① The onset area of middle cerebral artery was blocked for 2 hours, middle cerebral artery ischemia/reperfusion models were created.② After ischemia/reperfusion for 24 hours, cerebral tissue sections of rhesus monkeys were prepared and stained with cresyl violet. Image analysis was performed with 500IW

  5. Myocardial structure, function and ischaemic tolerance in a rodent model of obesity with insulin resistance.

    Science.gov (United States)

    Wensley, I; Salaveria, K; Bulmer, A C; Donner, D G; du Toit, E F

    2013-11-01

    Obesity and its comorbidities (dyslipidaemia, insulin resistance and hypertension) that together constitute the metabolic syndrome are all risk factors for ischaemic heart disease. Although obesity has been reported to be an independent risk factor for congestive heart failure, whether obesity-induced heart failure develops in the absence of increased afterload (induced by hypertension) is not clear. We have previously shown that obesity with insulin resistance decreases myocardial tolerance to ischaemia-reperfusion, but the mechanism for this decreased tolerance remains unclear. We hypothesize that obesity with insulin resistance induces adverse cardiac remodelling and pump dysfunction, as well as adverse changes in myocardial prosurvival reperfusion injury salvage kinase (RISK) pathway signalling to reduce myocardial tolerance to ischaemia-reperfusion. Wistar rats were fed an obesogenic (obese group) or a standard rat chow diet (control group) for 32 weeks. Echocardiography was performed over the 32 weeks before isolated Langendorff-perfused hearts were subjected to 40 min coronary artery ligation followed by reperfusion, and functional recovery (rate-pressure product), infarct size and RISK pathway function were assessed (Western blot analysis). Obesity with insulin resistance increased myocardial lipid accumulation but had no effect on in vivo or ex vivo left ventricular structure/function. Hearts from obese rats had lower reperfusion rate-pressure products (13115 ± 562 beats min(-1) mmHg for obese rats versus 17781 ± 1109 beats min(-1) mmHg for control rats, P < 0.05) and larger infarcts (36.3 ± 5.6% of area at risk in obese rats versus 14.1 ± 2.8% of area at risk in control rats, P < 0.01) compared with control hearts. These changes were associated with reductions in RISK pathway function, with 30-50 and 40-60% reductions in Akt and glycogen synthase kinase 3 beta (GSK-3β) expression and phosphorylation, respectively, in obese rat hearts compared with

  6. Balloon-assisted coil embolization of a posterior cerebral artery aneurysm via a persistent primitive trigeminal artery: technical note

    Energy Technology Data Exchange (ETDEWEB)

    Schlamann, Marc; Doerfler, Arnd; Forsting, Michael; Wanke, Isabel [University of Essen Medical School, Department of Neuroradiology, Institute of Diagnostic and Interventional Radiology, Essen (Germany); Schoch, Beate [University of Essen Medical School, Department of Neurosurgery, Essen (Germany)

    2006-12-15

    We present a patient with an acutely ruptured, wide-necked aneurysm of the left posterior cerebral artery (PCA) treated with Guglielmi detachable coils using the remodeling technique. Since the left vertebral artery was compressed due to a tumor in the cerebellopontine angle and the right vertebral artery was hypoplastic, we used a carotid artery approach via a persistent primitive trigeminal artery (PPTA) to selectively catheterize the aneurysm. The aneurysm was occluded completely. To our knowledge this is the first case of a wide-necked PCA aneurysm treated via a PPTA and using the remodeling technique. In patients with hypoplastic vertebral arteries and a PPTA, this approach may represent an alternative for selective embolization of posterior circulation aneurysms not amenable to the conventional approach. (orig.)

  7. Alteration in insulin action

    DEFF Research Database (Denmark)

    Tanti, J F; Gual, P; Grémeaux, T;

    2004-01-01

    Insulin resistance, when combined with impaired insulin secretion, contributes to the development of type 2 diabetes. Insulin resistance is characterised by a decrease in insulin effect on glucose transport in muscle and adipose tIssue. Tyrosine phosphorylation of insulin receptor substrate 1 (IR...

  8. Effect of postconditioning on dynamic expression of tenascin-C and left ventricular remodeling after myocardial ischemia and reperfusion

    OpenAIRE

    Taki, Junichi; Inaki, Anri; Wakabayashi, Hiroshi; Matsunari, Ichiro; Imanaka-Yoshida, Kyoko; Ogawa, Kazuma; Hiroe, Michiaki; Shiba, Kazuhiro; Yoshida, Toshimichi; Kinuya, Seigo

    2015-01-01

    Background Tenascin-C (TNC), an extracellular matrix glycoprotein, is expressed transiently in distinct areas in association with active tissue remodeling. This study aimed to explore how ischemic postconditioning (PC) affects myocardial expression of TNC and ventricular remodeling using 125I-labeled anti-TNC antibody (125I-TNC-Ab) in a rat model of ischemia and reperfusion. Methods In control rats (n = 27), the left coronary artery (LCA) was occluded for 30 min followed by reperfusion for 1,...

  9. Newer insulin analogues and inhaled insulin

    Directory of Open Access Journals (Sweden)

    Girish C

    2006-03-01

    Full Text Available Diabetes is a metabolic disease with high prevalence worldwide. Exogenous insulin is used in the management of this condition. The development of human insulin has provided tighter control of glycaemia in diabetic patients. Insulin analogues like insulin lispro and aspart were developed to closely match its profile with physiological secretion. The newer additions to this armamentarium are insulin glulisine, insulin detemir and albulin.Insulin glulisine is a short acting analogue with a rapid onset of action. The antiapoptotic property, mediated through insulin substrate receptor-2 has a favourable protective action on beta cells. Insulin detemir is a long acting analogue, soluble at neutral pH, which reversibly binds to albumin in plasma, prolonging its action. Its lower affinity for insulin receptors necessitates higher doses compared to human insulin. The reduction in body weight is an additional advantage of detemir. A major concern about all newer insulin analogues is their altered mitogenic properties and resultant risk of carcinogenicity on long term use. Albulin is a latest addition of insulin analogue which is under various in vitro and in vivo studies. Inhaled insulin in powder form (Exubera is recently approved by FDA and appears promising.

  10. Nonlinear Dynamics and Analysis of Intracranial Saccular Aneurysms with Growth and Remodeling

    Directory of Open Access Journals (Sweden)

    Manal Badgaish

    2016-01-01

    Full Text Available A new mathematical model for the interaction of blood flow with the arterial wall surrounded by cerebral spinal fluid is developed with applications to intracranial saccular aneurysms. The blood pressure acting on the inner arterial wall is modeled via a Fourier series, the arterial wall is modeled as a spring-mass system incorporating growth and remodeling, and the surrounding cerebral spinal fluid is modeled via a simplified one-dimensional compressible Euler equation with inviscid flow and negligible nonlinear effects. The resulting nonlinear coupled fluid-structure interaction problem is analyzed and a perturbation technique is employed to derive the first-order approximation solution to the system. An analytical solution is also derived for the linearized version of the problem using Laplace transforms. The solutions are validated against related work from the literature and the results suggest the biological significance of the inclusion of the growth and remodeling effects on the rupture of intracranial aneurysms.

  11. Insulin Resistance and Prediabetes

    Science.gov (United States)

    ... Disease Organizations (PDF, 293 KB). Alternate Language URL Insulin Resistance and Prediabetes Page Content On this page: ... Nutrition Points to Remember Clinical Trials What is insulin? Insulin is a hormone made in the pancreas, ...

  12. Insulin Human Inhalation

    Science.gov (United States)

    ... is a short-acting, man-made version of human insulin. Insulin inhalation works by replacing the insulin ... and selegiline (Eldepryl, Emsam, Zelapar); niacin; oral contraceptives (birth control pills); oral medications for diabetes such as pioglitazone ( ...

  13. Concentrated insulins: the new basal insulins

    Directory of Open Access Journals (Sweden)

    Lamos EM

    2016-03-01

    Full Text Available Elizabeth M Lamos,1 Lisa M Younk,2 Stephen N Davis3 1Division of Endocrinology, Diabetes and Nutrition, 2Department of Medicine, University of Maryland School of Medicine, 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA Introduction: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed. Areas covered: This review highlights the published reports of the pharmacokinetic (PK and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market. Conclusion: Humulin-R U500 has a similar onset but longer duration of action compared with U100 regular insulin. Insulin glargine U300 has differential PK/pharmacodynamic effects when compared with insulin glargine U100. In noninferiority studies, glycemic control with degludec U200 and glargine U300 is similar to insulin glargine U100 and nocturnal hypoglycemia is reduced. Concentrated formulations appear to behave as separate molecular entities when compared with earlier U100 insulin analog compounds. In the review of available published data, newer concentrated basal insulins may offer an advantage in terms of reduced intraindividual variability as well as reducing the injection burden in individuals requiring high-dose and large volume insulin therapy. Understanding the PK and pharmacodynamic properties of this new generation of insulins is critical to safe dosing, dispensing, and administration

  14. A possible link between endothelial dysfunction and insulin resistance in hypertension. A LIFE substudy. Losartan Intervention For Endpoint-Reduction in Hypertension

    DEFF Research Database (Denmark)

    Olsen, M H; Andersen, U B; Wachtell, K; Dige-Petersen, H; Ibsen, H

    We wanted to investigate whether insulin resistance and time to steady state during isoglycemic clamp were associated with endothelial dysfunction, peripheral vascular remodeling and forearm blood flow (FBF) in patients with longstanding hypertension....

  15. A possible link between endothelial dysfunction and insulin resistance in hypertension. A LIFE substudy. Losartan Intervention For Endpoint-Reduction in Hypertension

    DEFF Research Database (Denmark)

    Olsen, M H; Andersen, U B; Wachtell, K;

    2000-01-01

    We wanted to investigate whether insulin resistance and time to steady state during isoglycemic clamp were associated with endothelial dysfunction, peripheral vascular remodeling and forearm blood flow (FBF) in patients with longstanding hypertension....

  16. Effects of dynamicly adjusting insulin pump intake to control blood glucose after coronary artery bypass grafting%动态调节胰岛素泵入量在冠状动脉旁路移植术后血糖控制的效果评价

    Institute of Scientific and Technical Information of China (English)

    李娜; 生伟; 尹红

    2015-01-01

    ObjectiveTo discuss the effects of dynamicly adjusting insulin pump intake to control blood glucose after coronary artery bypass grafting(CABG).Methods A total of 121 patients undergoing coronary artery bypass surgery between October 2013 and October 2013 were divided into observation group(n=65)and control group (n=56). Insulin(40U Insulin+20mL normal saline )was infused by micro-pump in observation group,The amount of insulin was increased by 2U/h-4U/h before the meal,the insulin pump dose after two hours was adjusted according to the results of blood glucose.Insulin was infused by micro-pump according to the results of blood glucose in control group.Then the therapeutic effects of the two groups were assessed.Results There was no hypoglycemia occurred in the observation group and 5 cases in the control group,the difference was statistically significant(P<0.05).The blood glucose fluctuation was small and there was no wound infection,but there were 4 cases of wound infection in the control group, the difference was statistically significant(P<0.05).Conclusion Dynamic regulation of insulin pump in the amount of blood glucose control method,can effectively control blood glucose in the range of stability,reduce the incidence of complications after CABG operation,improve surgical treatment effect, and promote the rehabilitation of patients.%目的:探讨冠状动脉旁路移植术(CABG)后动态调节胰岛素泵入量控制血糖的效果。方法2013年10月~2014年10月选取就诊于青岛市市立医院心外科选择CABG的患者121例,随机分为观察组(65例)和对照组(56例),观察组术后给予微量泵持续注射普通胰岛素(40U胰岛素+20mL生理盐水),在患者进食前将胰岛素泵入量调高2~4U/h,在进食2h后,根据血糖结果再调整胰岛素泵入量。对照组根据血糖监测结果调整胰岛素泵入量,比较两组治疗效果。结果观察组术后无低血糖发生,对照组5例,

  17. Arterial Ageing

    OpenAIRE

    Lee, Seung-Jun; Park, Sung-Ha

    2013-01-01

    Arterial ageing is characterized by age associated degeneration and sclerosis of the media layer of the large arteries. However, besides ageing, clinical conditions, which enhance oxidative stress and inflammation act to accelerate the degree of arterial ageing. In this review, we summarized the pathophysiology and contributing factors that accelerate arterial ageing. Among them, we focused on hypertension, the renin-angiotensin-aldosterone system and vascular inflammation which are modifiabl...

  18. Relaxin mediates uterine artery compliance during pregnancy and increases uterine blood flow

    OpenAIRE

    Vodstrcil, Lenka A.; Tare, Marianne; Novak, Jacqueline; Dragomir, Nicoleta; Ramirez, Rolando J.; Wlodek, Mary E.; Conrad, Kirk P.; Parry, Laura J.

    2012-01-01

    Normal pregnancy involves dramatic remodeling of the uterine vasculature, with abnormal vascular adaptations contributing to pregnancy diseases such as preeclampsia. The peptide hormone relaxin is important for the renal and systemic hemodynamic adaptations to pregnancy, and has been shown to increase arterial compliance and outward hypertrophic remodeling. Therefore, we investigated the possibility that relaxin acts on its receptor, RXFP1, to mediate uterine artery compliance in late pregnan...

  19. Effect of exercise on insulin action in human skeletal muscle

    DEFF Research Database (Denmark)

    Richter, Erik; Mikines, K J; Galbo, Henrik;

    1989-01-01

    performed. Increased insulin action on glucose uptake was found in the exercised compared with the rested thigh at mean plasma insulin concentrations of 23, 40, and 410 microU/ml. Furthermore, prior contractions directed glucose uptake toward glycogen synthesis and increased insulin effects on thigh O2......The effect of 1 h of dynamic one-legged exercise on insulin action in human muscle was studied in 6 healthy young men. Four hours after one-legged knee extensions, a three-step sequential euglycemic hyperinsulinemic clamp combined with arterial and bilateral femoral vein catheterization was...... consumption and at some insulin concentrations on potassium exchange. In contrast, no change in insulin effects on limb exchange of free fatty acids, glycerol, alanine or tyrosine were found after exercise. Glycogen concentration in rested vastus lateralis muscle did not increase measurably during the clamp...

  20. Neural remodeling in retinal degeneration.

    Science.gov (United States)

    Marc, Robert E; Jones, Bryan W; Watt, Carl B; Strettoi, Enrica

    2003-09-01

    Mammalian retinal degenerations initiated by gene defects in rods, cones or the retinal pigmented epithelium (RPE) often trigger loss of the sensory retina, effectively leaving the neural retina deafferented. The neural retina responds to this challenge by remodeling, first by subtle changes in neuronal structure and later by large-scale reorganization. Retinal degenerations in the mammalian retina generally progress through three phases. Phase 1 initiates with expression of a primary insult, followed by phase 2 photoreceptor death that ablates the sensory retina via initial photoreceptor stress, phenotype deconstruction, irreversible stress and cell death, including bystander effects or loss of trophic support. The loss of cones heralds phase 3: a protracted period of global remodeling of the remnant neural retina. Remodeling resembles the responses of many CNS assemblies to deafferentation or trauma, and includes neuronal cell death, neuronal and glial migration, elaboration of new neurites and synapses, rewiring of retinal circuits, glial hypertrophy and the evolution of a fibrotic glial seal that isolates the remnant neural retina from the surviving RPE and choroid. In early phase 2, stressed photoreceptors sprout anomalous neurites that often reach the inner plexiform and ganglion cell layers. As death of rods and cones progresses, bipolar and horizontal cells are deafferented and retract most of their dendrites. Horizontal cells develop anomalous axonal processes and dendritic stalks that enter the inner plexiform layer. Dendrite truncation in rod bipolar cells is accompanied by revision of their macromolecular phenotype, including the loss of functioning mGluR6 transduction. After ablation of the sensory retina, Müller cells increase intermediate filament synthesis, forming a dense fibrotic layer in the remnant subretinal space. This layer invests the remnant retina and seals it from access via the choroidal route. Evidence of bipolar cell death begins in

  1. Acute arterial occlusion - kidney

    Science.gov (United States)

    ... arterial thrombosis; Renal artery embolism; Acute renal artery occlusion; Embolism - renal artery ... often result in permanent kidney failure. Acute arterial occlusion of the renal artery can occur after injury ...

  2. Axl, a receptor tyrosine kinase, mediates flow-induced vascular remodeling.

    Science.gov (United States)

    Korshunov, Vyacheslav A; Mohan, Amy M; Georger, Mary A; Berk, Bradford C

    2006-06-01

    Intima-media thickening (IMT) in response to hemodynamic stress is a physiological process that requires coordinated signaling among endothelial, inflammatory, and vascular smooth muscle cells (VSMC). Axl, a receptor tyrosine kinase, whose ligand is Gas6, is highly induced in VSMC after carotid injury. Because Axl regulates cell migration, phagocytosis and apoptosis, we hypothesized that Axl would play a role in IMT. Vascular remodeling in mice deficient in Axl (Axl(-/-)) and wild-type littermates (Axl(+/+)) was induced by ligation of the left carotid artery (LCA) branches maintaining flow via the left occipital artery. Both genotypes had similar baseline hemodynamic parameters and carotid artery structure. Partial ligation altered blood flow equally in both genotypes: increased by 60% in the right carotid artery (RCA) and decreased by 80% in the LCA. There were no significant differences in RCA remodeling between genotypes. However, in the LCA Axl(-/-) developed significantly smaller intima+media compared with Axl(+/+) (31+/-4 versus 42+/-6x10(-6) microm3, respectively). Quantitative immunohistochemistry of Axl(-/-) LCA showed increased apoptosis compared with Axl(+/+) (5-fold). As expected, p-Akt was decreased in Axl(-/-), whereas there was no difference in Gas6 expression. Cell composition also changed significantly, with increases in CD45+ cells and decreases in VSMC, macrophages, and neutrophils in Axl(-/-) compared with Axl(+/+). These data demonstrate an important role for Axl in flow-dependent remodeling by regulating vascular apoptosis and vascular inflammation. PMID:16627783

  3. Chromatin remodeling, development and disease

    International Nuclear Information System (INIS)

    Development is a stepwise process in which multi-potent progenitor cells undergo lineage commitment, differentiation, proliferation and maturation to produce mature cells with restricted developmental potentials. This process is directed by spatiotemporally distinct gene expression programs that allow cells to stringently orchestrate intricate transcriptional activation or silencing events. In eukaryotes, chromatin structure contributes to developmental progression as a blueprint for coordinated gene expression by actively participating in the regulation of gene expression. Changes in higher order chromatin structure or covalent modification of its components are considered to be critical events in dictating lineage-specific gene expression during development. Mammalian cells utilize multi-subunit nuclear complexes to alter chromatin structure. Histone-modifying complex catalyzes covalent modifications of histone tails including acetylation, methylation, phosphorylation and ubiquitination. ATP-dependent chromatin remodeling complex, which disrupts histone-DNA contacts and induces nucleosome mobilization, requires energy from ATP hydrolysis for its catalytic activity. Here, we discuss the diverse functions of ATP-dependent chromatin remodeling complexes during mammalian development. In particular, the roles of these complexes during embryonic and hematopoietic development are reviewed in depth. In addition, pathological conditions such as tumor development that are induced by mutation of several key subunits of the chromatin remodeling complex are discussed, together with possible mechanisms that underlie tumor suppression by the complex

  4. NEWER STRATEGIES FOR INSULIN DELIVERY

    OpenAIRE

    Singh Nisha; Lokwani Priyanka; Kaushik Avinash Yogendraji; Sharma Ritu

    2011-01-01

    Insulin is a proteinaceous hormone produced in the islets of Langerhans in the pancreas and used as a treatment in the diabetes mellitus. Successful oral insulin delivery involves overcoming the enzymatic and physical barriers and taking steps to conserve bioactivity during formulation processing. Newer strategies for insulin delivery include insulin pen injector, Refillable insulin injection pen, Insulin Syringe, Transfersome and Implantable insulin pumps.

  5. Insulin Resistance and Hyperinsulinemia

    OpenAIRE

    Kim, Sun H.; Reaven, Gerald M

    2008-01-01

    OBJECTIVE—Recently, it has been suggested that insulin resistance and hyperinsulinemia can exist in isolation and have differential impacts on cardiovascular disease (CVD). To evaluate this suggestion, we assessed the degree of discordance between insulin sensitivity and insulin response in a healthy, nondiabetic population. RESEARCH DESIGN AND METHODS—Insulin sensitivity was quantified by determining the steady-state plasma glucose (SSPG) concentration during an insulin suppression test in 4...

  6. Autoantibodies against human insulin.

    OpenAIRE

    Wilkin, T J; Nicholson, S.

    1984-01-01

    Sera from 680 non-diabetic subjects with suspected autoimmune disease were screened for 13 different antibodies. Of the 582 sera found to contain these antibodies, nine bound insulin in an IgG specific enzyme linked immunosorbent assay (micro ELISA). Four of the sera bound human, porcine, and bovine insulins and five bound exclusively human insulin. "Cold" human, porcine, and bovine insulins each displaced, in a dose dependent manner, the four sera which bound all three insulins, but only hum...

  7. Vascular remodeling and its role in the pathogenesis of ascites in fast growing commercial broilers.

    Science.gov (United States)

    Nain, S; Wojnarowicz, C; Laarveld, B; Olkowski, A A

    2009-06-01

    This study examined the putative role of blood vessel pathology in the development of ascites in broilers. Major blood vessels (aorta, brachiocephalic arteries, pulmonary arteries, and vena cava) from normal commercial male broiler chickens, and broilers that developed congestive heart failure (CHF) with or without ascites were subjected to gross and microscopic examination. On cross-section, grossly, the arteries from normal broilers and those showing dilated cardiomyopathy without ascites appeared circular, with firm wall tone characteristic of the normal artery. In contrast, the arteries from ascitic broilers appeared flaccid and lacked elasticity, which was evidenced by collapsing, ellipsoid cross-sectional arterial lumen owing to the structural weakness of the arterial walls. Microscopically, ascitic broilers showed thinning or occasionally total loss of elastic elements in the arterial wall, and reduced network density of the structural matrix of the vascular wall, as well as increased thickness of fibers in vena cava. The structural changes seen in the major arteries from ascitic broilers are maladaptive, and as such would definitively impose an increased hemodynamic burden on the already failing heart pump. The changes in veins are indicative of pathological remodeling conducive to increased permeability of the vascular wall, particularly in the situation when a poorly distensible structure is further subjected to wall stress associated with increased pressure and volume overload. Taken together, increased hemodynamic burden and reduced structural density of the venous wall constitute conditions conducive for seepage and accumulation of ascitic fluid. PMID:18947843

  8. Cardiac Remodeling After Atrial Fibrillation Ablation

    Directory of Open Access Journals (Sweden)

    Li-Wei Lo, MD; Shih-Ann Chen, MD

    2013-06-01

    Full Text Available Radiofrequency catheter ablation procedures are considered a reasonable option for patients with symptomatic, drug refractory atrial fibrillation (AF. Ablation procedures have been reported to effectively restore sinus rhythm and provide long-term relief of symptoms. Both electrical and structural remodeling occurs with AF. A reversal of the electrical remodeling develops within 1 week after restoration to sinus rhythm following the catheter ablation. The recovery rate is faster in the right atrium than the left atrium. Reverse structural remodeling takes longer and is still present 2 to 4 months after restoration of sinus rhythm. The left atrial transport function also improves after successful catheter ablation of AF. Left atrial strain surveys from echocardiography are able to identify patients who respond to catheter ablation with significant reverse remodeling after ablation. Pre-procedural delayed enhancement magnetic resonance imaging is also able to determine the degree of atrial fibrosis and is another tool to predict the reverse remodeling after ablation. The remodeling process is complex if recurrence develops after ablation. Recent evidence shows that a combined reverse electrical and structural remodeling occurs after ablation of chronic AF when recurrence is paroxysmal AF. Progressive electrical remodeling without any structural remodeling develops in those with recurrence involving chronic AF. Whether progressive atrial remodeling is the cause or consequence during the recurrence of AF remains obscure and requires further study.

  9. Vascular Stiffness in Insulin Resistance and Obesity

    Directory of Open Access Journals (Sweden)

    Guanghong eJia

    2015-08-01

    Full Text Available Obesity, insulin resistance, and type 2 diabetes are associated with a substantially increased prevalence of vascular fibrosis and stiffness, with attendant increased risk of cardiovascular and chronic kidney disease. Although the underlying mechanisms and mediators of vascular stiffness are not well understood, accumulating evidence supports the role of metabolic and immune dysregulation related to increased adiposity, activation of the renin angiotensin aldosterone system, reduced bioavailable nitric oxide, increased vascular extracellular matrix (ECM and ECM remodeling in the pathogenesis of vascular stiffness. This review will give a brief overview of the relationship between obesity, insulin resistance and increased vascular stiffness to provide a contemporary understanding of the proposed underlying mechanisms and potential therapeutic strategies.

  10. Estradiol Binds to Insulin and Insulin Receptor Decreasing Insulin Binding in vitro

    OpenAIRE

    RobertRoot-Bernstein

    2014-01-01

    Rationale: Insulin resistance associated with hyperestrogenemias occurs in gestational diabetes mellitus, polycystic ovary syndrome, ovarian hyperstimulation syndrome, estrogen therapies, metabolic syndrome and obesity. The mechanism by which insulin and estrogen interact is unknown. We hypothesize that estrogen binds directly to insulin and the insulin receptor producing insulin resistance. Objectives: To determine the binding constants of steroid hormones to insulin, the insulin recepto...

  11. Insulin pumps.

    Science.gov (United States)

    Pickup, J

    2011-02-01

    The last year has seen a continued uptake of insulin pump therapy in most countries. The USA is still a leader in pump use, with probably some 40% of type 1 diabetic patients on continuous subcutaneous insulin infusion (CSII), but the large variation in usage within Europe remains, with relatively high use (> 15%) in, for example, Norway, Austria, Germany and Sweden and low use (companies or funding from national health services, the availability of sufficient diabetes nurse educators and dietitians trained in pump procedures, and clear referral pathways for the pump candidate from general practitioner or general hospital to specialist pump centre. There are now several comprehensive national guidelines on CSII use (see ATTD Yearbook 2009) but more work needs to be done in unifying uptake and ensuring all those who can benefit do so. Technology developments recently include increasing use of pumps with continuous glucose monitoring (CGM) connectivity (see elsewhere in this volume) and the emergence of numerous manufacturers developing so-called 'patch pumps', often for the type 2 diabetes market. Interestingly, the evidence base for CSII in this group is not well established, and for this reason the selected papers on CSII in this section include several in this area. The use of CSII in diabetic pregnancy is a long-established practice, in spite of the lack of evidence that it is superior to multiple daily injections (MDI), and few randomised controlled trials have been done in recent years. Several papers in this field this year continue the debate about the usefulness of CSII in diabetic pregnancy and are reviewed here. It is pleasing to see more research on the psychosocial aspects of CSII during the year, both from the point of view of how psychological beliefs influence outcomes on CSII (is there a type of patient who does particularly well or poorly on CSII?) and how CSII affects psychological factors like mood, behaviour and quality of life. Quality of

  12. Adipose tissue remodeling: its role in energy metabolism and metabolic disorders

    Directory of Open Access Journals (Sweden)

    Sung Sik eChoe

    2016-04-01

    Full Text Available The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue (WAT functions as a key energy reservoir for other organs, whereas the brown adipose tissue (BAT accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secret various hormones, cytokines, and metabolites (termed as adipokines that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic over-nutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response.

  13. Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders.

    Science.gov (United States)

    Choe, Sung Sik; Huh, Jin Young; Hwang, In Jae; Kim, Jong In; Kim, Jae Bum

    2016-01-01

    The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue functions as a key energy reservoir for other organs, whereas the brown adipose tissue accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secrete various hormones, cytokines, and metabolites (termed as adipokines) that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue-resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic overnutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response. PMID:27148161

  14. Estrogen enhances vasoconstrictive remodeling after injury in male rabbits

    Directory of Open Access Journals (Sweden)

    Francisco Y.A.

    2005-01-01

    Full Text Available The complete spectrum of estrogen vascular effects remains unclear. In particular, estrogen effects in the vascular response to profound injury in males have not been explored in detail. Therefore, we submitted 44 male New Zealand rabbits weighing 3.4 ± 0.6 kg to overdistention balloon injury of the right iliac artery. Rabbits were given 17ß-estradiol (5.45 µmol/day, sc or vehicle for 7 days before and 14 days after injury, when the arteries were examined by post-mortem histomorphometry. Arteriographic caliber was assessed in vivo at baseline and before sacrifice. On day 14 after injury, in vivo arteriographic caliber (baseline = 2.44 ± 0.43 mm was decreased by 23.1 ± 0.1% in controls and by 44.5 ± 0.1% in estrogen-treated rabbits (P < 0.001. Neither the neointimal area nor the neointima/media area ratio changed after estrogen treatment. Collagen fraction was increased in the media and neointima of estrogen-treated rabbits vs control (1.38 ± 1.30 vs 0.35 ± 0.67, respectively, P = 0.01. Taken together, these findings suggest that estrogen increased negative vascular remodeling. Transcription of endothelial and inducible nitric oxide synthases (eNOS and iNOS was analyzed by RT-PCR. eNOS mRNA expression was marginally increased after estrogen (P = 0.07 and injury. iNOS mRNA was increased 2- to 3-fold on day 14 after injury. With estrogen treatment, iNOS mRNA increased in uninjured arteries and exhibited a further 5.5-fold increase after injury. We concluded that estrogen increased lumen loss after balloon injury in male rabbits, likely by increased negative remodeling, which may be related to increased iNOS transcriptional rates.

  15. Diabetes Mellitus, ArterialWall, and Cardiovascular Risk Assessment

    OpenAIRE

    Michaela Kozakova; Carlo Palombo

    2016-01-01

    Diabetes mellitus is an independent risk factor for atherothrombotic cardiovascular disease. Adults with diabetes are two to four times more likely to develop heart disease or stroke than adults without diabetes. The two major features of diabetes, i.e., hyperglycemia and insulin-resistance, trigger arterial stiffening and increase the susceptibility of the arterial wall to atherosclerosis at any given age. These pathological changes in the arterial wall may provide a functional and structura...

  16. Intranasal insulin therapy

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, S; Hvidberg, A;

    1995-01-01

    To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover...... randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more...... quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin was...

  17. Generalised insulin oedema after intensification of treatment with insulin analogues

    OpenAIRE

    Adamo, Luigi; Thoelke, Mark

    2013-01-01

    We report a case of generalised insulin oedema after intensification of treatment with genetically modified insulin. This is the first case of generalised oedema in response to treatment with insulin analogues in a patient not insulin naive.

  18. Human insulin genome sequence map, biochemical structure of insulin for recombinant DNA insulin.

    Science.gov (United States)

    Chakraborty, Chiranjib; Mungantiwar, Ashish A

    2003-08-01

    Insulin is a essential molecule for type I diabetes that is marketed by very few companies. It is the first molecule, which was made by recombinant technology; but the commercialization process is very difficult. Knowledge about biochemical structure of insulin and human insulin genome sequence map is pivotal to large scale manufacturing of recombinant DNA Insulin. This paper reviews human insulin genome sequence map, the amino acid sequence of porcine insulin, crystal structure of porcine insulin, insulin monomer, aggregation surfaces of insulin, conformational variation in the insulin monomer, insulin X-ray structures for recombinant DNA technology in the synthesis of human insulin in Escherichia coli. PMID:12769691

  19. The effect of chronic heart failure and type 2 diabetes on insulin-stimulated endothelial function is similar and additive

    DEFF Research Database (Denmark)

    Falskov, Britt; Hermann, Thomas Steffen; Rask-Madsen, Christian; Major-Pedersen, Atheline; Christiansen, Buris; Raunsø, Jakob; Køber, Lars; Torp-Pedersen, Christian; Dominguez, Helena

    2011-01-01

    AIM: Chronic heart failure is associated with endothelial dysfunction and insulin resistance. The aim of this investigation was to study insulin-stimulated endothelial function and glucose uptake in skeletal muscles in patients with heart failure in comparison to patients with type 2 diabetes...... plethysmography. Insulin-stimulated endothelial function was assessed after intra-arterial infusion of insulin followed by co-infusion with serotonin in three different dosages. Forearm glucose uptake was measured during the insulin infusion. RESULTS: Patients with systolic heart failure had impaired insulin...

  20. Levels of Circulating MMCN-151, a Degradation Product of Mimecan, Reflect Pathological Extracellular Matrix Remodeling in Apolipoprotein E Knockout Mice

    DEFF Research Database (Denmark)

    Barascuk, N; Vassiliadis, E; Zheng, Qiuju; Wang, Yu; Wang, W; Larsen, L; Rasmussen, L M; Karsdal, M A

    2011-01-01

    Arterial extracellular matrix (ECM) remodeling by matrix metalloproteinases (MMPs) is one of the major hallmarks of atherosclerosis. Mimecan, also known as osteoglycin has been implicated in the integrity of the ECM. This study assessed the validity of an enzyme-linked immunosorbent assay (ELISA...

  1. Cellular and Molecular Mechanisms of Bone Remodeling*

    OpenAIRE

    Raggatt, Liza J; Partridge, Nicola C

    2010-01-01

    Physiological bone remodeling is a highly coordinated process responsible for bone resorption and formation and is necessary to repair damaged bone and to maintain mineral homeostasis. In addition to the traditional bone cells (osteoclasts, osteoblasts, and osteocytes) that are necessary for bone remodeling, several immune cells have also been implicated in bone disease. This minireview discusses physiological bone remodeling, outlining the traditional bone biology dogma in light of emerging ...

  2. Cardiac electrical remodeling in health and disease

    OpenAIRE

    Cutler, Michael J.; Jeyaraj, Darwin; Rosenbaum, David S.

    2011-01-01

    Electrical remodeling of the heart occurs in response to both functional (i.e. altered electrical activation) and structural (i.e. heart failure, myocardial infarction, etc.) stressors. These electrophysiological changes produce a substrate that is vulnerable to malignant ventricular arrhythmias. Understanding the cellular and molecular mechanisms of electrical remodeling is important in elucidating potential therapeutic targets designed to alter maladaptive electrical remodeling. For example...

  3. Molecular Mechanisms of Insulin Resistance Development

    Directory of Open Access Journals (Sweden)

    Vsevolod Arsen'evich Tkachuk

    2014-05-01

    Full Text Available Insulin resistance (IR is a phenomenon associated with an impaired ability of insulin to stimulate glucose uptake by target cells and to reduce the blood glucose level. A response increase in insulin secretion by the pancreas and hyperinsulinemia are compensatory reactions of the body. The development of IR leads to the inability of target cells to respond to insulin that results in developing type 2 diabetes mellitus (T2DM and metabolic syndrome. For this reason, the metabolic syndrome is defined in practice as a combination of IR with one or more pathologies such as T2DM, arterial hypertension, dyslipidemia, abdominal obesity, non-alcoholic fatty liver disease, and some others. However, a combination of high blood glucose and insulin levels always serves as its physiological criterion.IR should be considered as a systemic failure of the endocrine regulation in the body. Physiological causes of IR are diverse. The main ones are nutritional overload and accumulation of certain lipids and their metabolites in cells, low physical activity, chronic inflammation and stress of various nature, including oxidative and endoplasmic reticulum stress (impairment of damaged protein degradation in the cell. Recent studies have demonstrated that these physiological mechanisms likely act through a single intracellular scenario. This is the impairment of signal transduction from the insulin receptor to its targets via the negative feedback mechanism in intracellular insulin-dependent signaling cascades.This review describes the physiological and intracellular mechanisms of insulin action and focuses on their abnormalities upon IR development. Finally, feasible trends in early molecular diagnosis and therapy of IR are discussed.

  4. Pressão arterial, respostas metabólicas e autonômicas à insulina e infusão de intralipid® em pacientes chagásicos Presión arterial, respuestas metabólicas y autonómicas a la insulina e infusión de intralipid® en pacientes chagásicos Blood pressure, metabolic and autonomic responses to insulin and intralipid® infusion in chagasic patients

    Directory of Open Access Journals (Sweden)

    Claudia Cristina Soares Silva

    2012-03-01

    con la forma indefinida de la Enfermedad de Chagas y 12 voluntarios sanos. RESULTADOS: La presión arterial basal y la frecuencia cardíaca fueron similares en los dos grupos. Los niveles plasmáticos de noradrenalina estaban ligeramente más elevados en el grupo de pacientes chagásicos. Después del Test de Tolerancia a la Insulina (TTI, se produjo una ostensible disminución en la glucosa de los dos grupos. La Infusión de ILH trajo como consecuencia el aumento de la presión arterial en ambos grupos, pero no hubo ningún cambio significativo en la noradrenalina plasmática. El componente de Baja Frecuencia (BF, fue similar y aumentó de forma parecida en ambos grupos. El componente de Alta Frecuencia (AF se presentó con un menor nivel en el grupo chagásico. CONCLUSIONES: Los pacientes con una forma indeterminada de la Enfermedad de Chagas, presentaron un aumento en la actividad simpática al momento basal y una respuesta inadecuada a la insulina. También tuvieron un menor componente de alta frecuencia y de sensibilidad barorrefleja, que fue perjudicado en el momento basal y durante la infusión de intralipid® y heparina.BACKGROUND: Intralipid and heparin infusion results in increased blood pressure and autonomic abnormalities in normal and hypertensive individuals. OBJECTIVE: To evaluate insulin sensitivity and the impact of Intralipid and heparin (ILH infusion on hemodynamic, metabolic, and autonomic response in patients with the indeterminate form of Chagas' disease. METHODS: Twelve patients with the indeterminate form of Chagas' disease and 12 healthy volunteers were evaluated. RESULTS: Baseline blood pressure and heart rate were similar in both groups. Plasma noradrenaline levels were slightly increased in the Chagas' group. After insulin tolerance testing (ITT, a significant decline was noted in glucose in both groups. ILH infusion resulted in increased blood pressure in both groups, but there was no significant change in plasma noradrenaline. The low

  5. I-123-insulin: A new marker for hepatoma

    Energy Technology Data Exchange (ETDEWEB)

    Sodoyez, J.C.; Goffaux, F.S.; Fallais, C.; Bourgeois, P.

    1984-01-01

    Previous studies have demonstrated that carrier-free I-123-Tyr Al4 insulin was taken up by the liver (by a saturable mechanism) and by the kidneys (by a non saturable mechanism). Autoradiographs of rat liver after injection of I-125-insulin showed that binding specifically occurred at the plasma membrane of the hepatocytes. I-123-Insulin binding to the hepatocyte plasma membrane appeared mediated by specific receptors. Indeed it was blocked by antibodies to the insulin receptors and by an excess of native insulin. Futhermore insulin derivatives with low biological potency (proinsulin and desoctapeptide insulin) did not inhibit I-123-insulin binding to the hepatocytes. I-123-Insulin (1.3 mCi) was I.V. injected into a patient in whom the right liver lobe was normal (normal uptake of Tc-99m-colloid sulfur) but the left liver lobe was occupied by a voluminous hepatoma (no uptake of Tc-99m-colloid sulfur). Liver blood supply was also studied by Tc-99m-pyrophosphate-labeled red cells. Computer analysis of the data revealed that compared to the normal liver lobe, binding of I-123-insulin to the hepatoma was more precocious (vascularization through the hepatic artery and not the portal vein), more intense and more prolonged (half-lives were 6 min in the normal liver and 14 min in the hepatoma). These results are consistent with characteristics of hepatoma cells in culture in which high insulin binding capacity contrasts with a markedly decreased insulin degrading activity. It is concluded that I-123-insulin may be used as a specific marker of hepatoma in man.

  6. I-123-insulin: A new marker for hepatoma

    International Nuclear Information System (INIS)

    Previous studies have demonstrated that carrier-free I-123-Tyr Al4 insulin was taken up by the liver (by a saturable mechanism) and by the kidneys (by a non saturable mechanism). Autoradiographs of rat liver after injection of I-125-insulin showed that binding specifically occurred at the plasma membrane of the hepatocytes. I-123-Insulin binding to the hepatocyte plasma membrane appeared mediated by specific receptors. Indeed it was blocked by antibodies to the insulin receptors and by an excess of native insulin. Futhermore insulin derivatives with low biological potency (proinsulin and desoctapeptide insulin) did not inhibit I-123-insulin binding to the hepatocytes. I-123-Insulin (1.3 mCi) was I.V. injected into a patient in whom the right liver lobe was normal (normal uptake of Tc-99m-colloid sulfur) but the left liver lobe was occupied by a voluminous hepatoma (no uptake of Tc-99m-colloid sulfur). Liver blood supply was also studied by Tc-99m-pyrophosphate-labeled red cells. Computer analysis of the data revealed that compared to the normal liver lobe, binding of I-123-insulin to the hepatoma was more precocious (vascularization through the hepatic artery and not the portal vein), more intense and more prolonged (half-lives were 6 min in the normal liver and 14 min in the hepatoma). These results are consistent with characteristics of hepatoma cells in culture in which high insulin binding capacity contrasts with a markedly decreased insulin degrading activity. It is concluded that I-123-insulin may be used as a specific marker of hepatoma in man

  7. Endothelin-1-mediated cerebrovascular remodeling is not associated with increased ischemic brain injury in diabetes

    OpenAIRE

    Li, Weiguo; Kelly-Cobbs, Aisha I.; Mezzetti, Erin M.; Fagan, Susan C; Ergul, Adviye

    2010-01-01

    Diabetes increases the risk as well as the poor outcome of stroke. Matrix metalloprotease (MMP) activation disrupts blood-brain barrier integrity after cerebral ischemia. We have previously shown that type 2 diabetes promotes remodeling of middle cerebral arteries (MCA) characterized by increased media:lumen (M/L) ratio and MMP activity in an endothelin (ET)-1-dependent manner in the Goto-Kakizaki (GK) rat model. In the present study, we examined the effects of ET-1-mediated vascular remodeli...

  8. Levothyroxine replacement therapy in patients with hypothyroidism, blood pressure and myocardial remodeling

    OpenAIRE

    D Kileinicov; Yu Orlov; V Masur; D Platonov; Masur, E.

    2011-01-01

    Our purpose was to investigate the short-term influence of thyroxin replacement therapy on arterial hypertension (AH) and heart remodeling in patients with primary hypothyroidism (PH). 52 patients with PH and AH received basic antihypertensive therapy unchanged during the period of study and individual l-thyroxin titration. All patients underwent echocardiography and daily blood pressure monitoring twice: in decompensation and after reaching euthyroid state in 3–4 months. Decrease in systolic...

  9. Cerebral blood flow links insulin resistance and baroreflex sensitivity.

    Directory of Open Access Journals (Sweden)

    John P Ryan

    Full Text Available Insulin resistance confers risk for diabetes mellitus and associates with a reduced capacity of the arterial baroreflex to regulate blood pressure. Importantly, several brain regions that comprise the central autonomic network, which controls the baroreflex, are also sensitive to the neuromodulatory effects of insulin. However, it is unknown whether peripheral insulin resistance relates to activity within central autonomic network regions, which may in turn relate to reduced baroreflex regulation. Accordingly, we tested whether resting cerebral blood flow within central autonomic regions statistically mediated the relationship between insulin resistance and an indirect indicator of baroreflex regulation; namely, baroreflex sensitivity. Subjects were 92 community-dwelling adults free of confounding medical illnesses (48 men, 30-50 years old who completed protocols to assess fasting insulin and glucose levels, resting baroreflex sensitivity, and resting cerebral blood flow. Baroreflex sensitivity was quantified by measuring the magnitude of spontaneous and sequential associations between beat-by-beat systolic blood pressure and heart rate changes. Individuals with greater insulin resistance, as measured by the homeostatic model assessment, exhibited reduced baroreflex sensitivity (b = -0.16, p < .05. Moreover, the relationship between insulin resistance and baroreflex sensitivity was statistically mediated by cerebral blood flow in central autonomic regions, including the insula and cingulate cortex (mediation coefficients < -0.06, p-values < .01. Activity within the central autonomic network may link insulin resistance to reduced baroreflex sensitivity. Our observations may help to characterize the neural pathways by which insulin resistance, and possibly diabetes mellitus, relates to adverse cardiovascular outcomes.

  10. Giving an insulin injection

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000660.htm Giving an insulin injection To use the sharing features on this ... and syringes. Filling the Syringe - One Type of Insulin Wash your hands with soap and water. Dry ...

  11. Insulin pump (image)

    Science.gov (United States)

    The catheter at the end of the insulin pump is inserted through a needle into the abdominal ... with diabetes. Dosage instructions are entered into the pump's small computer and the appropriate amount of insulin ...

  12. Insulin Lispro Injection

    Science.gov (United States)

    ... not use any type of insulin after the expiration date printed on the bottle has passed.Insulin ... sweating weakness muscle cramps abnormal heartbeat shortness of breath large weight gain in a short period of ...

  13. The Insulin Pump

    OpenAIRE

    Toews, C. J.

    1985-01-01

    Subcutaneous continuous insulin infusion systems deliver insulin at a basal rate designed to keep blood glucose levels normal in the non-fed state. Additional insulin is delivered at meal time. Pumps can provide near optimal control of blood glucose concentrations in selected, highly motivated patients. The pump provides better diabetic control than once daily insulin injections, although several daily injections can provide comparable control. Optimal control with the pump causes some short-...

  14. Insulin aspart pharmacokinetics

    DEFF Research Database (Denmark)

    Rasmussen, Christian Hove; Roge, Rikke Meldgaard; Ma, Zhulin;

    2014-01-01

    Background: Insulin aspart (IAsp) is used by many diabetics as a meal-time insulin to control postprandial glucose levels. As is the case with many other insulin types, the pharmacokinetics (PK), and consequently the pharmacodynamics (PD), is associated with clinical variability, both between and...

  15. Glycosphingolipids and insulin resistance

    NARCIS (Netherlands)

    M. Langeveld; J.F.M.G. Aerts

    2009-01-01

    Obesity is associated with an increased risk for insulin resistance, a state characterized by impaired responsiveness of liver, muscle and adipose tissue to insulin. One class of lipids involved in the development of insulin resistance are the (glyco)sphingolipids. Ceramide, the most simple sphingol

  16. Remodeling dan Repairing Vaskular pada Nefropati Hipertensif

    OpenAIRE

    Rasyid, Haerani; Wijaya, Johnson; Bakri, Syakib

    2011-01-01

    Latar Belakang: Ketidakseimbangan proses remodeling dan repairing vaskular diduga berperan penting pada kekakuan dan ketebalan vaskular yang akhirnya menyebabkan komplikasi hipertensi. Petanda dini komplikasi hipertensi pada ginjal adalah adanya mikroalbuminuria (MA). Tujuan Penelitian: Untuk mengetahui perbedaan konsentrasi TGF-??1 (sebagai petanda remodeling) dan VEGFR-2 (sebagai petanda repairing) pada subyek normotensi, hipertensi normoalbuminuria (NA) dan hipertensi MA. Metode: P...

  17. Multiscale Simulation of Protein Mediated Membrane Remodeling

    OpenAIRE

    Ayton, Gary S.; Voth, Gregory A.

    2009-01-01

    Proteins interacting with membranes can result in substantial membrane deformations and curvatures. This effect is known in its broadest terms as membrane remodeling. This review article will survey current multiscale simulation methodologies that have been employed to examine protein-mediated membrane remodeling.

  18. Nucleosome dynamics during chromatin remodeling in vivo.

    Science.gov (United States)

    Ramachandran, Srinivas; Henikoff, Steven

    2016-01-01

    Precise positioning of nucleosomes around regulatory sites is achieved by the action of chromatin remodelers, which use the energy of ATP to slide, evict or change the composition of nucleosomes. Chromatin remodelers act to bind nucleosomes, disrupt histone-DNA interactions and translocate the DNA around the histone core to reposition nucleosomes. Hence, remodeling is expected to involve nucleosomal intermediates with a structural organization that is distinct from intact nucleosomes. We describe the identification of a partially unwrapped nucleosome structure using methods that map histone-DNA contacts genome-wide. This alternative nucleosome structure is likely formed as an intermediate or by-product during nucleosome remodeling by the RSC complex. Identification of the loss of histone-DNA contacts during chromatin remodeling by RSC in vivo has implications for the regulation of transcriptional initiation. PMID:26933790

  19. Phosphodiesterase 10A upregulation contributes to pulmonary vascular remodeling.

    Science.gov (United States)

    Tian, Xia; Vroom, Christina; Ghofrani, Hossein Ardeschir; Weissmann, Norbert; Bieniek, Ewa; Grimminger, Friedrich; Seeger, Werner; Schermuly, Ralph Theo; Pullamsetti, Soni Savai

    2011-01-01

    Phosphodiesterases (PDEs) modulate the cellular proliferation involved in the pathophysiology of pulmonary hypertension (PH) by hydrolyzing cAMP and cGMP. The present study was designed to determine whether any of the recently identified PDEs (PDE7-PDE11) contribute to progressive pulmonary vascular remodeling in PH. All in vitro experiments were performed with lung tissue or pulmonary arterial smooth muscle cells (PASMCs) obtained from control rats or monocrotaline (MCT)-induced pulmonary hypertensive (MCT-PH) rats, and we examined the effects of the PDE10 inhibitor papaverine (Pap) and specific small interfering RNA (siRNA). In addition, papaverine was administrated to MCT-induced PH rats from day 21 to day 35 by continuous intravenous infusion to examine the in vivo effects of PDE10A inhibition. We found that PDE10A was predominantly present in the lung vasculature, and the mRNA, protein, and activity levels of PDE10A were all significantly increased in MCT PASMCs compared with control PASMCs. Papaverine and PDE10A siRNA induced an accumulation of intracellular cAMP, activated cAMP response element binding protein and attenuated PASMC proliferation. Intravenous infusion of papaverine in MCT-PH rats resulted in a 40%-50% attenuation of the effects on pulmonary hypertensive hemodynamic parameters and pulmonary vascular remodeling. The present study is the first to demonstrate a central role of PDE10A in progressive pulmonary vascular remodeling, and the results suggest a novel therapeutic approach for the treatment of PH. PMID:21494592

  20. Insulin enhances glucose-stimulated insulin secretion in healthy humans

    OpenAIRE

    Bouche, Clara; Lopez, Ximena; Fleischman, Amy; Cypess, Aaron M.; O'Shea, Sheila; Stefanovski, Darko; Bergman, Richard N.; Rogatsky, Eduard; Stein, Daniel T.; Kahn, C. Ronald; Kulkarni, Rohit N.; Goldfine, Allison B.

    2010-01-01

    Islet β-cells express both insulin receptors and insulin-signaling proteins. Recent evidence from rodents in vivo and from islets isolated from rodents or humans suggests that the insulin signaling pathway is physiologically important for glucose sensing. We evaluated whether insulin regulates β-cell function in healthy humans in vivo. Glucose-induced insulin secretion was assessed in healthy humans following 4-h saline (low insulin/sham clamp) or isoglycemic-hyperinsulinemic (high insulin) c...

  1. Thyroid Hormone and Vascular Remodeling.

    Science.gov (United States)

    Ichiki, Toshihiro

    2016-03-01

    Both hyperthyroidism and hypothyroidism affect the cardiovascular system. Hypothyroidism is known to be associated with enhanced atherosclerosis and ischemic heart diseases. The accelerated atherosclerosis in the hypothyroid state has been traditionally ascribed to atherogenic lipid profile, diastolic hypertension, and impaired endothelial function. However, recent studies indicate that thyroid hormone has direct anti-atherosclerotic effects, such as production of nitric oxide and suppression of smooth muscle cell proliferation. These data suggest that thyroid hormone inhibits atherogenesis through direct effects on the vasculature as well as modification of risk factors for atherosclerosis. This review summarizes the basic and clinical studies on the role of thyroid hormone in vascular remodeling. The possible application of thyroid hormone mimetics to the therapy of hypercholesterolemia and atherosclerosis is also discussed. PMID:26558400

  2. Remodelling of choroidal blood flow in radiation choroidopathy

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Hideo; Muraoka, Kanemitsu; Takahashi, Kyoichi; Sutoh, Noriko [Gunma Univ., Maebashi (Japan). School of Medicine

    1997-02-01

    Two males, aged 68 and 34 years each, presented with radiation retinopathy. One had received radiation therapy to the whole brain for intracranial metastasis of lung carcinoma 29 months before. The other underwent surgery and radiation for melanoma of the upper eyelid 15 years before. When examined by indocyanine green angiography. both cases showed vasoocclusive changes in the choroid involving the choriocapillaris and major vessels in the affected fundus area. In one eye with severe retinal vascular lesions in the superior temporal quadrant, the vortex vein in the quadrant had obliterated. The venous blood in this quadrant was drained into the inferior temporal vortex vein crossing the presumed watershed zone temporal to the macula. Collaterals had formed between choroidal arteries and between choroidal veins. These cases illustrate that choroidal vascular lesions may be present in radiation retinopathy, that the former may be more pronounced than the latter and that choroidal vessels may undergo extensive remodelling to compensate for the disturbed choroidal circulation. (author)

  3. Metformin and insulin receptors

    International Nuclear Information System (INIS)

    The authors evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific 125I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific 125I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin. Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects and diabetic patients. Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded

  4. Observations of super early left ventricular remodeling experimental myocardial infarction

    International Nuclear Information System (INIS)

    Purpose: Ventricular remodeling is defined as the changes in the shape and size of the entire left ventricle after acute myocardial infarction (AMI). Many investigators have shown that left ventricular remodeling is related to clinical outcomes, including mortality, that represent the natural history, of the heart failure syndrome. The aim of this study was to demonstrate that it is possible to observe super early left ventricular remodeling by 99mTc-MIBI myocardial imaging in the dog model of acute experimental myocardial infarction. Methods: Experimental subjects: Twenty-three healthy mongrel dogs (14-25 kg) of either sex were studied under general anesthesia (sodium pentobarbital, 30 mg/kg). The left anterior descending (LAD) coronary artery was dissected and ligated between the first and second diagonal branches. Seven dogs died of ventricular fibrillation after the LAD coronary artery ligation. The 16 remaining dogs were divided into two groups: Group A (GA) received 99mTc-MIBI myocardial imaging (n=8): Group B (GB) received 99mTc-MIBI myocardial imaging combined with echocardiography (n=8). 99mTc-MIBI myocardial perfusion imaging :Static 99mTc-MIBI myocardial imaging was taken with ADAC Vertex Dual-head SPECT. 99mTc-MIBI kit was manufactured in Syncor, China. Each dog served as its own control, and was scanned by 99mTc-MIBI myocardial imaging and chocardiography at 48-72 hours before ligation. The mean time of the first acquisition was 21.87 ± 11.03 (14-48) minutes post-operatively in GA, 57.63±22.83 (30-99) minutes for 99mTc-MIBI imaging in GB, 26.00±15.07 (12-50) minutes for echocardiography in GB. Acquisition techniques for Gated SPECT: ECG synchronized data collection: R wave trigger, 8 Frames/Cardiac cycle. Images were gathered by rotating the detectors 180 degrees at 6 degrees per frame. Each frame took 40 seconds. The dog position was supine. The images were acquired and recorded for 6 hours following the LAD coronary artery ligation. After 6 hours

  5. Remodeling in the ischemic heart: the stepwise progression for heart

    Directory of Open Access Journals (Sweden)

    J.G. Mill

    2011-09-01

    Full Text Available Abstract Coronary artery disease is the leading cause of death in the developed world and in developing countries. Acute mortality from acute myocardial infarction (MI has decreased in the last decades. However, the incidence of heart failure (HF in patients with healed infarcted areas is increasing. Therefore, HF prevention is a major challenge to the health system in order to reduce healthcare costs and to provide a better quality of life. Animal models of ischemia and infarction have been essential in providing precise information regarding cardiac remodeling. Several of these changes are maladaptive, and they progressively lead to ventricular dilatation and predispose to the development of arrhythmias, HF and death. These events depend on cell death due to necrosis and apoptosis and on activation of the inflammatory response soon after MI. Systemic and local neurohumoral activation has also been associated with maladaptive cardiac remodeling, predisposing to HF. In this review, we provide a timely description of the cardiovascular alterations that occur after MI at the cellular, neurohumoral and electrical level and discuss the repercussions of these alterations on electrical, mechanical and structural dysfunction of the heart. We also identify several areas where insufficient knowledge limits the adoption of better strategies to prevent HF development in chronically infarcted individuals.

  6. Energetic and spatial constraints of arterial networks

    Directory of Open Access Journals (Sweden)

    Sandro Rossitti

    1995-06-01

    Full Text Available The principle of minimum work (PMW is a parametric optimization model for the growth and adaptation of arterial trees. A balance between energy dissipation due to frictional resistance of laminar flow (shear stress and the minimum volume of the blood and vessel wall tissue is achieved when the vessel radii are adjusted to the cube root of the volumetric flow. The PMW is known to apply over several magnitudes of vessel calibers, and in many different organs, including the brain, in humans and in animals. Animal studies suggest that blood flow in arteries is approximately proportional to the cube of the vessel radius, and that arteries alter their caliber in response to sustained changes of blood flow according to PMW. Remodelling of the retinal arteriolar network to long-term changes in blood flow was observed in humans. Remodelling of whole arterial networks occurs in the form of increase or diminishing of vessel calibers. Shear stress induced endothelial mediation seems to be the regulating mechanism for the maintenance of this optimum blood flow/vessel diameter relation. Arterial trees are also expected to be nearly space filing. The vascular system is constructed in such a way that, while blood vessels occupy only a small percentage of the body volume leaving the bulk to tissue, they also crisscross organs so tightly that every point in the tissue lies on the boundary between an artery and a vein. This review describes how the energetic optimum principle for least energy cost for blood flow is also compatible with the spatial constraints of arterial networks according to concepts derived from fractal geometry.

  7. Analysis of Arterial Mechanics During Head-Down-Tilt Bed Rest

    Science.gov (United States)

    Elliott, Morgan B.; Martin, David S.; Westby, Christian M.; Stenger, Michael B.; Platts, Steven H.

    2014-01-01

    Carotid, brachial, and tibial arteries reacted differently to HDTBR. Previous studies have not analyzed the mechanical properties of the human brachial or anterior tibial arteries. After slight variations during bed-rest, arterial mechanical properties and IMT returned to pre-bed rest values, with the exception of tibial stiffness and PSE, which continued to be reduced post-bed rest while the DC remained elevated. The tibial artery remodeling was probably due to decreased pressure and volume. Resulting implications for longer duration spaceflight are unclear. Arterial health may be affected by microgravity, as shown by increased thoracic aorta stiffness in other ground based simulations (Aubert).

  8. Cerebral blood flow links insulin resistance and baroreflex sensitivity.

    Science.gov (United States)

    Ryan, John P; Sheu, Lei K; Verstynen, Timothy D; Onyewuenyi, Ikechukwu C; Gianaros, Peter J

    2013-01-01

    Insulin resistance confers risk for diabetes mellitus and associates with a reduced capacity of the arterial baroreflex to regulate blood pressure. Importantly, several brain regions that comprise the central autonomic network, which controls the baroreflex, are also sensitive to the neuromodulatory effects of insulin. However, it is unknown whether peripheral insulin resistance relates to activity within central autonomic network regions, which may in turn relate to reduced baroreflex regulation. Accordingly, we tested whether resting cerebral blood flow within central autonomic regions statistically mediated the relationship between insulin resistance and an indirect indicator of baroreflex regulation; namely, baroreflex sensitivity. Subjects were 92 community-dwelling adults free of confounding medical illnesses (48 men, 30-50 years old) who completed protocols to assess fasting insulin and glucose levels, resting baroreflex sensitivity, and resting cerebral blood flow. Baroreflex sensitivity was quantified by measuring the magnitude of spontaneous and sequential associations between beat-by-beat systolic blood pressure and heart rate changes. Individuals with greater insulin resistance, as measured by the homeostatic model assessment, exhibited reduced baroreflex sensitivity (b = -0.16, p mediated by cerebral blood flow in central autonomic regions, including the insula and cingulate cortex (mediation coefficients < -0.06, p-values < .01). Activity within the central autonomic network may link insulin resistance to reduced baroreflex sensitivity. Our observations may help to characterize the neural pathways by which insulin resistance, and possibly diabetes mellitus, relates to adverse cardiovascular outcomes. PMID:24358272

  9. Deficiency of Nox2 prevents angiotensin II-induced inward remodeling in cerebral arterioles

    Directory of Open Access Journals (Sweden)

    Siu-Lung eChan

    2013-06-01

    Full Text Available Angiotensin II is an important determinant of inward remodeling in cerebral arterioles. Many of the vascular effects of angiotensin II are mediated by reactive oxygen species generated from homologues of NADPH oxidase with Nox2 predominating in small arteries and arterioles. Therefore, we tested the hypothesis that superoxide generated by Nox2 plays a role in angiotensin II-induced cerebral arteriolar remodeling. We examined Nox2-deficient and wild-type mice in which a pressor or a non-pressor dose of angiotensin II (1000 or 200 ng/kg/day or saline was infused for 4 weeks via osmotic minipumps. Systolic arterial pressure was measured by a tail-cuff method. Pressure and diameter of cerebral arterioles were measured through an open cranial window in anesthetized mice. Cross-sectional area (by histology and superoxide level (by hydroethidine staining of cerebral arterioles were determined ex vivo. The pressor, but not the non-pressor, dose of angiotensin II significantly increased systolic arterial pressure in both wild-type and Nox2-deficient mice. Both doses of angiotensin II increased superoxide levels and significantly reduced external diameter in maximally dilated cerebral arterioles in wild-type mice. Increased superoxide and inward remodeling were prevented in Nox2-deficient mice. Moreover, only the pressor dose of AngII increased cross-sectional area of arteriolar wall in wild-type mice and was prevented in Nox2-deficient mice. In conclusion, superoxide derived from Nox2-containing NADPH oxidase plays an important role in angiotensin II-mediated inward remodeling in cerebral arterioles. This effect appears to be independent of pressure and different from that of hypertrophy.

  10. Cholinergic Regulation of Airway Inflammation and Remodelling

    Directory of Open Access Journals (Sweden)

    Saeed Kolahian

    2012-01-01

    Full Text Available Acetylcholine is the predominant parasympathetic neurotransmitter in the airways that regulates bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine regulates additional functions in the airways, including inflammation and remodelling during inflammatory airway diseases. Moreover, it has become apparent that acetylcholine is synthesized by nonneuronal cells and tissues, including inflammatory cells and structural cells. In this paper, we will discuss the regulatory role of acetylcholine in inflammation and remodelling in which we will focus on the role of the airway smooth muscle cell as a target cell for acetylcholine that modulates inflammation and remodelling during respiratory diseases such as asthma and COPD.

  11. Insulin and insulin signaling play a critical role in fat induction of insulin resistance in mouse

    OpenAIRE

    Ning, Jie; Hong, Tao; Yang, Xuefeng; Mei, Shuang; Liu, Zhenqi; Liu, Hui-Yu; Cao, Wenhong

    2011-01-01

    The primary player that induces insulin resistance has not been established. Here, we studied whether or not fat can cause insulin resistance in the presence of insulin deficiency. Our results showed that high-fat diet (HFD) induced insulin resistance in C57BL/6 (B6) mice. The HFD-induced insulin resistance was prevented largely by the streptozotocin (STZ)-induced moderate insulin deficiency. The STZ-induced insulin deficiency prevented the HFD-induced ectopic fat accumulation and oxidative s...

  12. Allergy reactions to insulin: effects of continuous subcutaneous insulin infusion and insulin analogues.

    OpenAIRE

    RADERMECKER, Régis; Scheen, André

    2007-01-01

    The purification of animal insulin preparations and the use of human recombinant insulin have markedly reduced the incidence but not completely suppressed the occurrence of insulin allergy manifestations. Advances in technologies concerning the mode of delivery of insulin, i.e. continuous subcutaneous insulin infusion (CSII), and the use of insulin analogues, resulting from the alteration in the amino acid sequence of the native insulin molecule, may influence the immunogenicity and antigenic...

  13. Insulin analogs and cancer

    Directory of Open Access Journals (Sweden)

    Laura eSciacca

    2012-02-01

    Full Text Available Today, insulin analogs are used in millions of diabetic patients. Insulin analogs have been developed to achieve more physiological insulin replacement in terms of time course of the effect. Modifications in the amino acid sequence of the insulin molecule change the pharmacokinetics and pharmacodynamics of the analogs in respect to human insulin. However, these changes can also modify the molecular and biological effects of the analogs. The rapid-acting insulin analogs, lispro, aspart and glulisine, have a rapid onset and shorter duration of action. The long-acting insulin analogs glargine and detemir have a protracted duration of action and a relatively smooth serum concentration profile. Insulin and its analogs may function as growth factors and therefore have a theoretical potential to promote tumor proliferation. A major question is whether analogs have an increased mitogenic activity in respect to insulin. These ligands can promote cell proliferation through many mechanisms like the prolonged stimulation of the insulin receptor, stimulation of the IGF-1 receptor (IGF-1R, prevalent activation of the ERK rather than the AKT intracellular post-receptor pathways. Studies on in vitro models indicate that short-acting analogs elicit molecular and biological effects that are similar to those of insulin. In contrast, long-acting analogs behave differently. Although not all data are homogeneous, both glargine and detemir have been found to have a decreased binding to IR but an increased binding to IGF-1R, a prevalent activation of the ERK pathway, and an increased mitogenic effect in respect to insulin. Recent retrospective epidemiological clinical studies have suggested that treatment with long-acting analogs (specifically glargine may increase the relative risk for cancer. Results are controversial and methodologically weak. Therefore prospective clinical studies are needed to evaluate the possible tumor growth-promoting effects of these insulin

  14. Rat liver insulin receptor

    International Nuclear Information System (INIS)

    Using insulin affinity chromatography, the authors have isolated highly purified insulin receptor from rat liver. When evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions, the rat liver receptor contained the M/sub r/ 125,000 α-subunit, the M/sub r/ 90,000 β-subunit, and varying proportions of the M/sub r/ 45,000 β'-subunit. The specific insulin binding of the purified receptor was 25-30 μg of 125I-insulin/mg of protein, and the receptor underwent insulin-dependent autophosphorylation. Rat liver and human placental receptors differ from each other in several functional aspects: (1) the adsorption-desorption behavior from four insulin affinity columns indicated that the rat liver receptor binds less firmly to immobilized ligands; (2) the 125I-insulin binding affinity of the rat liver receptor is lower than that of the placental receptor; (3) partial reduction of the rat liver receptor with dithiothreitol increases its insulin binding affinity whereas the binding affinity of the placental receptor is unchanged; (4) at optimal insulin concentration, rat liver receptor autophosphorylation is stimulated 25-50-fold whereas the placental receptor is stimulated only 4-6-fold. Conversion of the β-subunit to β' by proteolysis is a major problem that occurs during exposure of the receptor to the pH 5.0 buffer used to elute the insulin affinity column. Proteolytic destruction and the accompanying loss of insulin-dependent autophosphorylation can be substantially reduced by proteolysis inhibitors. In summary, rat liver and human placental receptors differ functionally in both α- and β-subunits. Insulin binding to the α-subunit of the purified rat liver receptor communicates a signal that activates the β-subunit; however, major proteolytic destruction of the β-subunit does not affect insulin binding to the α-subunit

  15. Interleukin-2/Anti-Interleukin-2 Immune Complex Attenuates Cardiac Remodeling after Myocardial Infarction through Expansion of Regulatory T Cells

    OpenAIRE

    Zhipeng Zeng; Kunwu Yu; Long Chen; Weihua Li; Hong Xiao; Zhengrong Huang

    2016-01-01

    CD4+CD25+Foxp3+ regulatory T cells (Treg cells) have protective effects in wound healing and adverse ventricular remodeling after myocardial infarction (MI). We hypothesize that the interleukin- (IL-) 2 complex comprising the recombinant mouse IL-2/anti-IL-2 mAb (JES6-1) attenuates cardiac remodeling after MI through the expansion of Treg. Mice were subjected to surgical left anterior descending coronary artery ligation and treated with either PBS or IL-2 complex. The IL-2 complex significant...

  16. Evaluation of left ventricular remodelling in patients with chronic ischemic heart disease using multislice computer tomography and magnetic resonance tomography

    International Nuclear Information System (INIS)

    The article presents the results of MSCT and MRI of the heart in 57 patients with chronic coronary heart disease. It determined the relationship between structural and functional changes in the left ventricle and the degree of left coronary artery stenosis. Also determined were the link between the ischemic left ventricular remodeling and depth of myocardial damage in patients with coronary heart disease and postinfarction cardiosclerosis. MSCT and MRI are highly reliable imaging technique used to evaluate the infarcted and viable myocardium and post infarct cardiac remodeling process

  17. Concentrated insulins: the new basal insulins

    OpenAIRE

    Lamos EM; Younk LM; Davis SN

    2016-01-01

    Elizabeth M Lamos,1 Lisa M Younk,2 Stephen N Davis3 1Division of Endocrinology, Diabetes and Nutrition, 2Department of Medicine, University of Maryland School of Medicine, 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA Introduction: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with in...

  18. Blood pressure, sodium intake, insulin resistance, and urinary nitrate excretion.

    Science.gov (United States)

    Facchini, F S; DoNascimento, C; Reaven, G M; Yip, J W; Ni, X P; Humphreys, M H

    1999-04-01

    The objective of this study was to investigate the relationships among various humoral factors thought to be involved in the regulation of blood pressure during high NaCl intake. Nineteen healthy subjects underwent sequential 5-day periods ingesting a low-sodium (25 mmol/d) or high-sodium (200 mmol/d) diet. Insulin resistance was assessed by the steady-state plasma glucose concentration at the end of a 3-hour insulin suppression test. Insulin resistance correlated inversely with natriuresis (P=0.04) and directly with increase in weight (P=0.03). The increase in mean arterial pressure associated with the high-sodium diet correlated directly with the gain in weight (P<0.05) and inversely with the increase in urinary nitrate excretion (P<0.0001). In a multiple regression model, more than 2/3 of the variance in mean arterial pressure was accounted for by the gain in weight and change in urinary nitrate excretion. The steady-state plasma glucose concentrations obtained with the 2 diets were similar, indicating that insulin resistance was unaffected by sodium intake. During high sodium intake, plasma renin activity and aldosterone decreased and plasma atrial natriuretic peptide increased; these changes did not correlate with the change in mean arterial pressure, insulin resistance, or change in urinary nitrate excretion. To the extent that urinary nitrate excretion reflects activity of the endogenous nitric oxide system, these results suggest that the salt sensitivity of mean arterial pressure may be related to blunted generation of endogenous nitric oxide. The results also demonstrate that insulin-resistant individuals have an impaired natriuretic response to high sodium intake. PMID:10205239

  19. Classifying insulin regimens

    DEFF Research Database (Denmark)

    Neu, A; Lange, K; Barrett, T;

    2015-01-01

    Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1...... diabetes there is little distinctiveness about concepts and the nomenclature is confusing. Even among experts similar terms are used for different strategies. The aim of our review--based on the experiences of the Hvidoere Study Group (HSG)--is to propose comprehensive definitions for current insulin...... variety of insulin regimens applied in each center, respectively. Furthermore, the understanding of insulin regimens has been persistently different between the centers since more than 20 yr. Not even the terms 'conventional' and 'intensified therapy' were used consistently among all members. Besides the...

  20. Flexibility in insulin prescription

    Science.gov (United States)

    Kalra, Sanjay; Gupta, Yashdeep; Unnikrishnan, Ambika Gopalakrishnan

    2016-01-01

    This communication explores the concept of flexibility, a propos insulin preparations and insulin regimes used in the management of type 2 diabetes. The flexibility of an insulin regime or preparation is defined as their ability to be injected at variable times, with variable injection-meal time gaps, in a dose frequency and quantum determined by shared decision making, with a minimal requirement of glucose monitoring and health professional consultation, with no compromise on safety, efficiency and tolerability. The relative flexibility of various basal, prandial and dual action insulins, as well as intensive regimes, is compared. The biopsychosocial model of health is used to assess the utility of different insulins while encouraging a philosophy of flexible insulin usage. PMID:27186563

  1. Flexibility in insulin prescription.

    Science.gov (United States)

    Kalra, Sanjay; Gupta, Yashdeep; Unnikrishnan, Ambika Gopalakrishnan

    2016-01-01

    This communication explores the concept of flexibility, a propos insulin preparations and insulin regimes used in the management of type 2 diabetes. The flexibility of an insulin regime or preparation is defined as their ability to be injected at variable times, with variable injection-meal time gaps, in a dose frequency and quantum determined by shared decision making, with a minimal requirement of glucose monitoring and health professional consultation, with no compromise on safety, efficiency and tolerability. The relative flexibility of various basal, prandial and dual action insulins, as well as intensive regimes, is compared. The biopsychosocial model of health is used to assess the utility of different insulins while encouraging a philosophy of flexible insulin usage. PMID:27186563

  2. Flexibility in insulin prescription

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2016-01-01

    Full Text Available This communication explores the concept of flexibility, a propos insulin preparations and insulin regimes used in the management of type 2 diabetes. The flexibility of an insulin regime or preparation is defined as their ability to be injected at variable times, with variable injection-meal time gaps, in a dose frequency and quantum determined by shared decision making, with a minimal requirement of glucose monitoring and health professional consultation, with no compromise on safety, efficiency and tolerability. The relative flexibility of various basal, prandial and dual action insulins, as well as intensive regimes, is compared. The biopsychosocial model of health is used to assess the utility of different insulins while encouraging a philosophy of flexible insulin usage.

  3. Transforming Growth Factor-β1 Induces Transdifferentiation of Fibroblasts into Myofibroblasts in Hypoxic Pulmonary Vascular Remodeling

    Institute of Scientific and Technical Information of China (English)

    Yong-Liang JIANG; Ai-Guo DAI; Qi-Fang LI; Rui-Cheng HU

    2006-01-01

    The muscularization of non-muscular pulmonary arterioles is animportant pathological feature of hypoxic pulmonary vascular remodeling. However, the origin of the cells involved in this process is still not well understood. The present study was undertaken to test the hypothesis that transforming growth factor-β 1 (TGF-β 1) can induce transdifferentiation of fibroblasts into myofibroblasts, which might play a key role in the muscularization of non-muscular pulmonary arterioles. It was found that mean pulmonary arterial pressure increased significantly after 7 d of hypoxia. Pulmonary artery remodeling index and right ventricular hypertrophy became evident after 14 d of hypoxia. The distribution of nonmuscular, partially muscular, and muscular vessels was significantly different after 7 d of hypoxia. Immunocytochemistry results demonstrated that the expression of α-smooth muscle actin was increased in intra-acinar pulmonary arteries with increasing hypoxic time. TGF-β1 mRNA expression in pulmonary arterial walls was increased significantly after 14 d of hypoxia, but showed no obvious changes after 3 or 7 d of hypoxia. In pulmonary tunica adventitia and tunica media, TGF-β1 protein staining was poorly positive in control rats, but was markedly enhanced after 3 d of hypoxia, reaching its peak after 7 d of hypoxia. The myofibroblast phenotype was confirmed by electron microscopy, which revealed microfilaments and a well-developed rough endoplasmic reticulum. Taken together, our results suggested that TGF-β1 induces transdifferentiation of fibroblasts into myofibroblasts, which is important in hypoxic pulmonary vascular remodeling.

  4. Etiopathogenesis of insulin autoimmunity.

    OpenAIRE

    Åke Lenmark; Moustakas, Antonis K; Papadopoulos, George K; Norio Kanatsuna

    2012-01-01

    Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (pro)insulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining lymphnodes. Recent data on proinsulin peptide binding to type 1 diabetes-associated HLA-DQ2 and ...

  5. Insulin sensitivity and albuminuria

    DEFF Research Database (Denmark)

    Pilz, Stefan; Rutters, Femke; Nijpels, Giel;

    2014-01-01

    assessed by hyperinsulinemic-euglycemic clamps, expressed as the M/I value. Oral glucose tolerance test-based insulin sensitivity (OGIS), homeostasis model assessment of insulin resistance (HOMA-IR), and urinary albumin-to-creatinine ratio (UACR) were determined at baseline and follow-up. RESULTS...... albuminuria. This finding suggests that reduced insulin sensitivity either is simply related to or might causally contribute to the initial pathogenesis of albuminuria....

  6. AMPK and insulin action

    DEFF Research Database (Denmark)

    Frøsig, Christian; Jensen, Thomas Elbenhardt; Jeppesen, Jacob;

    2013-01-01

    and insulin stimulated glucose uptake in both the soleus and extensor digitorum longus muscle, coinciding with reduced insulin signaling at the level of Akt (pSer473 and pThr308), TBC1D1 (pThr590) and TBC1D4 (pThr642). In contrast to our hypothesis, the impact of ageing and high fat diet on insulin action...

  7. Carotid Artery Screening

    Science.gov (United States)

    ... Resources Professions Site Index A-Z Carotid Artery Screening What is carotid artery screening? Who should consider ... about carotid artery screening? What is carotid artery screening? Screening examinations are tests performed to find disease ...

  8. Maxillary Mucocele with Orbital Floor Remodelling

    OpenAIRE

    Tahrina Salam; Maryam Zamani; Jane Olver

    2012-01-01

    A 79-year-old man presents with signs of an orbital mass. A CT scan revealed a large maxillary mucocele eroding through the orbital floor. Surgical drainage of the mucocele and conservative postoperative care, returned all ophthalmic signs to normal and bony remodelling of the orbital floor was demonstrated. Maxillary mucoceles should be assessed by both ENT and Ophthalmic surgeons. Postoperative remodelling of the orbital floor can be illustrated with serial CT Scans.

  9. Human ultralente insulin.

    OpenAIRE

    Holman, R R; Steemson, J; Darling, P; Reeves, W G; Turner, R.C.

    1984-01-01

    The greater solubility of human insulin and its possible faster action have led to doubts about whether a sufficiently long acting formulation could be produced to provide a basal supply for diabetics. In a double blind crossover study in 18 diabetics human ultralente insulin was as effective as beef ultralente insulin in controlling basal plasma glucose concentrations (median 5.7 mmol/l (103 mg/100 ml) with human and 6.3 mmol/l (114 mg/100 ml) with beef ultralente insulin respectively). Ther...

  10. Binding of insulin to rat pancreatic islets: comparison between pancreatic human insulin and biosynthetic human insulin

    Energy Technology Data Exchange (ETDEWEB)

    Verspohl, E.J.; Ammon, H.P.

    Human pancreatic insulin, biosynthetic human insulin (BHI), and pork insulin were compared in terms of their binding characteristics to insulin receptors on rat pancreatic islets. There was no difference in binding or on biologic effect, i.e., ability to inhibit insulin secretion.

  11. Eccentric exercise decreases maximal insulin action in humans

    DEFF Research Database (Denmark)

    Asp, Svend; Daugaard, J R; Kristiansen, S;

    1996-01-01

    1. Unaccustomed eccentric exercise decreases whole-body insulin action in humans. To study the effects of one-legged eccentric exercise on insulin action in muscle and systemically, the euglycaemic clamp technique combined with arterial and bilateral femoral venous catheterization was used. Seven...... subjects participated in two euglycaemic clamps, performed in random order. One clamp was preceded 2 days earlier by one-legged eccentric exercise (post-eccentric exercise clamp (PEC)) and one was without the prior exercise (control clamp (CC)). 2. During PEC the maximal insulin-stimulated glucose uptake...... over the eccentric thigh was marginally lower when compared with the control thigh, (11.9%, 64.6 +/- 10.3 vs. 73.3 +/- 10.2 mumol kg-1 min-1, P = 0.08), whereas no inter-thigh difference was observed at a submaximal insulin concentration. The glycogen concentration was lower in the eccentric thigh for...

  12. Insulin action in human thighs after one-legged immobilization

    DEFF Research Database (Denmark)

    Richter, Erik; Kiens, Bente; Mizuno, M.;

    1989-01-01

    Insulin action was assessed in thighs of five healthy young males who had one knee immobilized for 7 days by a splint. The splint was not worn in bed. Subjects also used crutches to prevent weight bearing of the immobilized leg. Immobilization decreased the activity of citrate synthase and 3-OH......-acyl-CoA-dehydrogenase in the vastus lateralis muscle by 9 and 14%, respectively, and thigh volume by 5%. After 7 days of immobilization, a two-step euglycemic hyperinsulinemic clamp procedure combined with arterial and bilateral femoral venous catheterization was performed. Insulin action on glucose uptake and tyrosine...... release of the thighs at mean plasma insulin concentrations of 67 (clamp step I) and 447 microU/ml (clamp step II) was decreased by immobilization, whereas immobilization did not affect insulin action on thigh exchange of free fatty acids, glycerol, O2, or potassium. Before and during the clamp step I...

  13. Dynamics of the ethanolamine glycerophospholipid remodeling network.

    Directory of Open Access Journals (Sweden)

    Lu Zhang

    Full Text Available Acyl chain remodeling in lipids is a critical biochemical process that plays a central role in disease. However, remodeling remains poorly understood, despite massive increases in lipidomic data. In this work, we determine the dynamic network of ethanolamine glycerophospholipid (PE remodeling, using data from pulse-chase experiments and a novel bioinformatic network inference approach. The model uses a set of ordinary differential equations based on the assumptions that (1 sn1 and sn2 acyl positions are independently remodeled; (2 remodeling reaction rates are constant over time; and (3 acyl donor concentrations are constant. We use a novel fast and accurate two-step algorithm to automatically infer model parameters and their values. This is the first such method applicable to dynamic phospholipid lipidomic data. Our inference procedure closely fits experimental measurements and shows strong cross-validation across six independent experiments with distinct deuterium-labeled PE precursors, demonstrating the validity of our assumptions. In contrast, fits of randomized data or fits using random model parameters are worse. A key outcome is that we are able to robustly distinguish deacylation and reacylation kinetics of individual acyl chain types at the sn1 and sn2 positions, explaining the established prevalence of saturated and unsaturated chains in the respective positions. The present study thus demonstrates that dynamic acyl chain remodeling processes can be reliably determined from dynamic lipidomic data.

  14. Diagnostic tools assessing airway remodelling in asthma.

    Science.gov (United States)

    Manso, L; Reche, M; Padial, M A; Valbuena, T; Pascual, C

    2012-01-01

    Asthma is an inflammatory disease of the lower airways characterised by the presence of airway inflammation, reversible airflow obstruction and airway hyperresponsiveness and alterations on the normal structure of the airways, known as remodelling. Remodelling is characterised by the presence of metaplasia of mucous glands, thickening of the lamina reticularis, increased angiogenesis, subepithelial fibrosis and smooth muscle hypertrophy/hyperplasia. Several techniques are being optimised at present to achieve a suitable diagnosis for remodelling. Diagnostic tools could be divided into two groups, namely invasive and non-invasive methods. Invasive techniques bring us information about bronchial structural alterations, obtaining this information directly from pathological tissue, and permit measure histological modification placed in bronchi layers as well as inflammatory and fibrotic cell infiltration. Non-invasive techniques were developed to reduce invasive methods disadvantages and measure airway remodelling-related markers such as cytokines, inflammatory mediators and others. An exhaustive review of diagnostic tools used to analyse airway remodelling in asthma, including the most useful and usually employed methods, as well as the principal advantages and disadvantages of each of them, bring us concrete and summarised information about all techniques used to evaluate alterations on the structure of the airways. A deep knowledge of these diagnostic tools will make an early diagnosis of airway remodelling possible and, probably, early diagnosis will play an important role in the near future of asthma. PMID:22236733

  15. Anti-insulin antibody test

    Science.gov (United States)

    Insulin antibodies - serum; Insulin Ab test ... Normally, there are no antibodies against insulin in your blood. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or ...

  16. Alternative Devices for Taking Insulin

    Science.gov (United States)

    ... KB). Alternate Language URL Alternative Devices for Taking Insulin Page Content On this page: What alternative devices ... the skin. [ Top ] What alternative devices for taking insulin are available? Insulin pens provide a convenient, easy- ...

  17. Immunologic and inflammatory mechanisms that drive asthma progression to remodeling

    OpenAIRE

    Broide, David H.

    2008-01-01

    Although histologic features of airway remodeling have been well characterized in asthma, the immunologic and inflammatory mechanisms that drive progression of asthma to remodeling are still incompletely understood. Conceptually, airway remodeling may be due to persistent inflammation and/or aberrant tissue repair mechanisms. It is likely that several immune and inflammatory cell types and mediators are involved in mediating airway remodeling. In addition, different features of airway remodel...

  18. Perivascular adipose tissue control of insulin-induced vasoreactivity in muscle is impaired in db/db mice

    DEFF Research Database (Denmark)

    Meijer, Rick I; Bakker, Wineke; Alta, Caro-Lynn A F;

    2013-01-01

    Microvascular recruitment in muscle is a determinant of insulin sensitivity. Whether perivascular adipose tissue (PVAT) is involved in disturbed insulin-induced vasoreactivity is unknown, as are the underlying mechanisms. This study investigates whether PVAT regulates insulin-induced vasodilation...... in muscle, the underlying mechanisms, and how obesity disturbs this vasodilation. Insulin-induced vasoreactivity of resistance arteries was studied with PVAT from C57BL/6 or db/db mice. PVAT weight in muscle was higher in db/db mice compared with C57BL/6 mice. PVAT from C57BL/6 mice uncovered insulin......-induced vasodilation; this vasodilation was abrogated with PVAT from db/db mice. Blocking adiponectin abolished the vasodilator effect of insulin in the presence of C57BL/6 PVAT, and adiponectin secretion was lower in db/db PVAT. To investigate this interaction further, resistance arteries of AMPKa2(+/+) and AMPKa2...

  19. A Semi-Automated Quantification of Pulmonary Artery Dimensions in Computed Tomography Angiography Images

    OpenAIRE

    Berty, Holly L.; Simon, Marc; Chapman, Brian E.

    2012-01-01

    Quantifying vascular dimensions may provide a non-invasive means of diagnosing a variety of vascular diseases, including pulmonary hypertension, a progressive, potentially fatal disease that results in the remodeling of the pulmonary vasculature. Currently the gold standard for diagnosis of pulmonary hypertension is through right heart catheterization, an invasive and costly procedure. Since pulmonary hypertension is associated with the remodeling of the pulmonary arteries, quantifying vascul...

  20. The Relationship of Body Composition and Coronary Artery Calcification in Apparently Healthy Korean Adults

    OpenAIRE

    Yu, Jung-Hee; Yim, Seo Hyoung; Yu, Su Hyeon; Lee, Ji Yong; Kim, Jong Dae; Seo, Mi Hae; Jeon, Won Seon; Park, Se-Eun; Park, Cheol-Young; Lee, Won-Young; Oh, Ki-Won; Park, Sung-Woo; Rhee, Eun-Jung

    2013-01-01

    Background We investigated the association of coronary artery calcium score (CACS) with body composition and insulin resistance in apparently healthy Korean adults. Methods Nine hundred forty-five participants (mean age, 48.9 years; 628 men) in a medical check-up program were selected for analysis. Body composition was assessed by bioelectrical impedance analysis (BIA). Insulin resistance was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR). The CACS was assess...

  1. Proliferation of pulmonary artery smooth muscle cells in the development of ascites syndrome in broilers induced by low ambient temperature.

    Science.gov (United States)

    Wang, J; Qiao, J; Zhao, L H; Li, K; Wang, H; Xu, T; Tian, Y; Gao, M; Wang, X

    2007-12-01

    Pulmonary vascular remodelling, mainly characterized by arterial medial thickening, is an important pathological feature of broiler ascites syndrome (AS). Since vascular smooth muscle cells (VSMC) form the major cellular component of arterial medial layer, we speculate that VSMC proliferation is one of the causes of pulmonary arterial medial thickening in ascitic broilers. Hence, the present study was designed to investigate the role of VSMC proliferation in pulmonary vascular remodelling in development of AS induced by low ambient temperature. Broilers in control group (22 +/- 1.5 degrees C) and low temperature group (11 +/- 2 degrees C) were sampled every week at 15-50 days of age. Proliferative indexes of VSMC in pulmonary arteries were assessed with proliferating cell nuclear antigen, and the relative medial thickness (RMT) and relative wall area (RWA), as indexes of pulmonary vascular remodelling, were examined by computer-image analysing system. The results showed that the high incidence (18.75%) of AS was induced by low temperature, and a significantly increased VSMC proliferation was observed in pulmonary arteries in the low temperature group at 22-50 days of age (P < 0.05). In addition, RMT and RWA in pulmonary arteries were significantly elevated in the low temperature group from 36 days of age (P < 0.05), indicating that pulmonary vascular remodelling occurred following VSMC proliferation in AS. Our data suggest that proliferation of VSMC may facilitate pulmonary vascular remodelling and have a pivotal role in AS induced by low ambient temperature. PMID:18045340

  2. Diabetes Mellitus, Arterial Wall, and Cardiovascular Risk Assessment

    Science.gov (United States)

    Kozakova, Michaela; Palombo, Carlo

    2016-01-01

    Diabetes mellitus is an independent risk factor for atherothrombotic cardiovascular disease. Adults with diabetes are two to four times more likely to develop heart disease or stroke than adults without diabetes. The two major features of diabetes, i.e., hyperglycemia and insulin-resistance, trigger arterial stiffening and increase the susceptibility of the arterial wall to atherosclerosis at any given age. These pathological changes in the arterial wall may provide a functional and structural background for cardiovascular events. The present paper provides a critical overview of the clinical evidence linking diabetes-related metabolic abnormalities to cardiovascular risk, debates the pathophysiologic mechanisms through which insulin resistance and hyperglycemia may affect the arterial wall, and discusses the associations between vascular biomarkers, metabolic abnormalities and cardiovascular events. PMID:26861377

  3. Cardiac remodelling and RAS inhibition.

    Science.gov (United States)

    Ferrario, Carlos M

    2016-06-01

    Risk factors such as hypertension and diabetes are known to augment the activity and tissue expression of angiotensin II (Ang II), the major effector peptide of the renin-angiotensin system (RAS). Overstimulation of the RAS has been implicated in a chain of events that contribute to the pathogenesis of cardiovascular (CV) disease, including the development of cardiac remodelling. This chain of events has been termed the CV continuum. The concept of CV disease existing as a continuum was first proposed in 1991 and it is believed that intervention at any point within the continuum can modify disease progression. Treatment with antihypertensive agents may result in regression of left ventricular hypertrophy, with different drug classes exhibiting different degrees of efficacy. The greatest decrease in left ventricular mass is observed following treatment with angiotensin converting enzyme inhibitors (ACE-Is), which inhibit Ang II formation. Although ACE-Is and angiotensin receptor blockers (ARBs) provide significant benefits in terms of CV events and stroke, mortality remains high. This is partly due to a failure to completely suppress the RAS, and, as our knowledge has increased, an escape phenomenon has been proposed whereby the human sequence of the 12 amino acid substrate angiotensin-(1-12) is converted to Ang II by the mast cell protease, chymase. Angiotensin-(1-12) is abundant in a wide range of organs and has been shown to increase blood pressure in animal models, an effect abolished by the presence of ACE-Is or ARBs. This review explores the CV continuum, in addition to examining the influence of the RAS. We also consider novel pathways within the RAS and how new therapeutic approaches that target this are required to further reduce Ang II formation, and so provide patients with additional benefits from a more complete blockade of the RAS. PMID:27105891

  4. Characteristics of arterial hypertension in obesity

    Directory of Open Access Journals (Sweden)

    Ivković-Lazar Tatjana A.

    2004-01-01

    Full Text Available Introduction Arterial hypertension is the most frequent cardiovascular disease in obese persons, progressing with time to left ventricular hypertension, often associated with dilatation, diastolic disorders, hearth rhythm disturbance, and generalized atherosclerosis. Etiology The origin of this disease is related to hemodynamic disturbances (increased blood volume, minute volume, mainly due to increased stroke volume accompanied with changes of peripheral resistance, which increases in a later phase. However, metabolic factors are presently considered as primarily responsible for appearance of hypertension, which has rightly obtained the attribute of metabolic hypertension. A key role belongs to insulin, in fact, to insulin resistance and hyperinsulinism. Treatment Awareness of the metabolic basis of arterial hypertension in obesity has resulted in a specific approach to its treatment. The primary treatment includes reduction diet, with a drastic reduction of salt intake and with compulsory physical activity, while concerning medications one should consider converting enzyme inhibitors, alpha1 blockers and calcium channel antagonists. .

  5. Rule-based model of vein graft remodeling.

    Directory of Open Access Journals (Sweden)

    Minki Hwang

    Full Text Available When vein segments are implanted into the arterial system for use in arterial bypass grafting, adaptation to the higher pressure and flow of the arterial system is accomplished thorough wall thickening and expansion. These early remodeling events have been found to be closely coupled to the local hemodynamic forces, such as shear stress and wall tension, and are believed to be the foundation for later vein graft failure. To further our mechanistic understanding of the cellular and extracellular interactions that lead to global changes in tissue architecture, a rule-based modeling method is developed through the application of basic rules of behaviors for these molecular and cellular activities. In the current method, smooth muscle cell (SMC, extracellular matrix (ECM, and monocytes are selected as the three components that occupy the elements of a grid system that comprise the developing vein graft intima. The probabilities of the cellular behaviors are developed based on data extracted from in vivo experiments. At each time step, the various probabilities are computed and applied to the SMC and ECM elements to determine their next physical state and behavior. One- and two-dimensional models are developed to test and validate the computational approach. The importance of monocyte infiltration, and the associated effect in augmenting extracellular matrix deposition, was evaluated and found to be an important component in model development. Final model validation is performed using an independent set of experiments, where model predictions of intimal growth are evaluated against experimental data obtained from the complex geometry and shear stress patterns offered by a mid-graft focal stenosis, where simulation results show good agreements with the experimental data.

  6. Anaphylaxis to protamine masquerading as an insulin allergy.

    Science.gov (United States)

    Kim, R

    1993-01-01

    This is the case of a 62-year-old man referred for the evaluation of insulin allergy. This patient had reacted to the subcutaneous injection of Novolin 70/30 (Squibb, Princeton, N.J.) and Humulin NPH (Eli Lilly, Indianapolis, Ind.). These reactions were characterized by the immediate onset of diffuse pruritic urticaria and angioedema with progression to hypotension as well as a local reaction. Past history also included anaphylactic shock after intravenous administration of protamine sulfate used for heparin reversal during arterial bypass surgery. Immediate hypersensitivty skin testing to protamine containing (NPH) insulin and protamine sulfate USP were strongly positive, while Lente insulin (Eli Lilly, Indianapolis, Ind.) and controls were negative. RAST tests revealed the titers > 24 ng/ml of protamine specific IgE with 98 percent inhibition and 1163 ng/ml of protamine specific IgG with 29 percent inhibition, while levels of insulin specific antibodies were negligible. Subsequently, the patient was treated with non-protamine containing insulin preparation, Lente insulin, without further incident. This study confirms the diagnosis of Type I hypersensitivity to protamine sulfate masquerading as insulin allergy. PMID:8454092

  7. Cocoa, glucose tolerance, and insulin signaling: cardiometabolic protection.

    Science.gov (United States)

    Grassi, Davide; Desideri, Giovambattista; Mai, Francesca; Martella, Letizia; De Feo, Martina; Soddu, Daniele; Fellini, Emanuela; Veneri, Mariangela; Stamerra, Cosimo A; Ferri, Claudio

    2015-11-18

    Experimental and clinical evidence reported that some polyphenol-rich natural products may offer opportunities for the prevention and treatment of type 2 diabetes, due to their biological properties. Natural products have been suggested to modulate carbohydrate metabolism by various mechanisms, such as restoring β-cell integrity and physiology and enhancing insulin-releasing activity and glucose uptake. Endothelium is fundamental in regulating arterial function, whereas insulin resistance plays a pivotal role in pathophysiological mechanisms of prediabetic and diabetic states. Glucose and insulin actions in the skeletal muscle are improved by insulin-dependent production of nitric oxide, favoring capillary recruitment, vasodilatation, and increased blood flow. Endothelial dysfunction, with decreased nitric oxide bioavailability, is a critical step in the development of atherosclerosis. Furthermore, insulin resistance has been described, at least in part, to negatively affect endothelial function. Consistent with this, conditions of insulin resistance are usually linked to endothelial dysfunction, and the exposure of the endothelial cells to cardiovascular risk factors such as hypertension, dyslipidemia, and hyperglycemia is associated with reduced nitric oxide bioavailability, resulting in impaired endothelial-dependent vasodilatation. Moreover, endothelial dysfunction has been described as an independent predictor of cardiovascular risk and events. Cocoa and cocoa flavonoids may positively affect the pathophysiological mechanisms involved in insulin resistance and endothelial dysfunction with possible benefits in the prevention of cardiometabolic diseases. PMID:26126077

  8. A simple way to identify insulin resistance in non-diabetic acute coronary syndrome patients with impaired fasting glucose

    OpenAIRE

    Sayantan Ray; Ashit Kumar Bairagi; Santanu Guha; Satyabrata Ganguly; Debes Ray; Ashis Kumar Basu; Anirban Sinha

    2012-01-01

    Background and Objective: The incidence of coronary artery disease (CAD) is increasing in India. Recent data suggesting insulin resistance can predict cardiovascular disease independently of the other risk factors, such as hypertension, visceral obesity, or dyslipidemia, so a focus on the relation between acute coronary syndrome (ACS) and insulin resistance is relevant. Several studies addressing serum lipoprotein ratios as surrogates for insulin resistance have found promising results. We an...

  9. Relationship of Insulin Sensitivity, Insulin Secretion, and Adiposity With Insulin Clearance in a Multiethnic Population

    OpenAIRE

    Lorenzo, Carlos; Hanley, Anthony J.G.; Wagenknecht, Lynne E; Rewers, Marian J.; Stefanovski, Darko; Goodarzi, Mark O.; Haffner, Steven M

    2012-01-01

    OBJECTIVE We aimed to examine insulin clearance, a compensatory mechanism to changes in insulin sensitivity, across sex, race/ethnicity populations, and varying states of glucose tolerance. RESEARCH DESIGN AND METHODS We measured insulin sensitivity index (S I), acute insulin response (AIR), and metabolic clearance rate of insulin (MCRI) by the frequently sampled intravenous glucose tolerance test in 1,295 participants in the Insulin Resistance Atherosclerosis Study. RESULTS MCRI was positive...

  10. Metabolic programming in the pathogenesis of insulin resistance.

    Science.gov (United States)

    Devaskar, Sherin U; Thamotharan, Manikkavasagar

    2007-06-01

    This review focuses on different animal models of nutrient perturbations, inclusive of restrictive and excessive states mimicking human situations during pregnancy and lactation that cause aberrations in the offspring. These aberrations consist of diminished insulin sensitivity in the presence of defective insulin production. These phenotypic changes are due to altered peripheral tissue post-insulin receptor signaling mechanisms and pancreatic beta-islet insulin synthesis and secretion defects. While these changes during in utero or postnatal life serve as essential adaptations to overcome adverse conditions, they become maladaptive subsequently and set the stage for type 2 diabetes mellitus. Pregnancy leads to gestational diabetes with trans-generational propagation of the insulin resistant phenotype. This is in response to the metabolically aberrant maternal in utero environment, and tissue specific epigenetic perturbations that permanently alter expression of critical genes transmitted to future generations. These heritable aberrations consisting of altered DNA methylation and histone modifications remodel chromatin and affect transcription of key genes. Along with an altered in utero environment, these chromatin modifications contribute to the world-wide epidemic of type 2 diabetes mellitus, with nutrient excess dominating in developed and nutrient restriction in developing countries. PMID:17657604

  11. Insulin Resistance of Puberty.

    Science.gov (United States)

    Kelsey, Megan M; Zeitler, Philip S

    2016-07-01

    Puberty is a time of considerable metabolic and hormonal change. Notably, puberty is associated with a marked decrease in insulin sensitivity, on par with that seen during pregnancy. In otherwise healthy youth, there is a nadir in insulin sensitivity in mid-puberty, and then it recovers at puberty completion. However, there is evidence that insulin resistance (IR) does not resolve in youth who are obese going into puberty and may result in increased cardiometabolic risk. Little is known about the underlying pathophysiology of IR in puberty, and how it might contribute to increased disease risk (e.g., type 2 diabetes). In this review, we have outlined what is known about the IR in puberty in terms of pattern, potential underlying mechanisms and other mediating factors. We also outline other potentially related metabolic changes that occur during puberty, and effects of underlying insulin resistant states (e.g., obesity) on pubertal changes in insulin sensitivity. PMID:27179965

  12. Diabetes, insulin and exercise

    DEFF Research Database (Denmark)

    Richter, Erik; Galbo, H

    1986-01-01

    The metabolic and hormonal adaptations to single exercise sessions and to exercise training in normal man and in patients with insulin-dependent as well as non-insulin-dependent diabetes mellitus are reviewed. In insulin-dependent (type I) diabetes good metabolic control is best obtained...... by a regular pattern of life which will lead to a fairly constant demand for insulin from day to day. Exercise is by nature a perturbation that makes treatment of diabetes difficult: Muscle contractions per se tend to decrease the plasma glucose concentration whereas the exercise-induced response of the so...... not be recommended as a means of improving metabolic control in insulin-dependent diabetes. However, our present knowledge and technology allows the well-informed and cooperative patient to exercise and even to reach the elite level. To achieve this, pre-exercise metabolic control should be optimal and knowledge...

  13. Insulin and the Lung

    DEFF Research Database (Denmark)

    Singh, Suchita; Prakash, Y S; Linneberg, Allan;

    2013-01-01

    , molecular understanding is necessary. Insulin resistance is a strong, independent risk factor for asthma development, but it is unknown whether a direct effect of insulin on the lung is involved. This review summarizes current knowledge regarding the effect of insulin on cellular components of the lung......Obesity, metabolic syndrome, and asthma are all rapidly increasing globally. Substantial emerging evidence suggests that these three conditions are epidemiologically and mechanistically linked. Since the link between obesity and asthma appears to extend beyond mechanical pulmonary disadvantage...... and highlights the molecular consequences of insulin-related metabolic signaling cascades that could adversely affect lung structure and function. Examples include airway smooth muscle proliferation and contractility and regulatory signaling networks that are associated with asthma. These aspects of insulin...

  14. Regulation of the insulin-like growth factor system by insulin in burn patients.

    Science.gov (United States)

    Lang, C H; Fan, J; Frost, R A; Gelato, M C; Sakurai, Y; Herndon, D N; Wolfe, R R

    1996-07-01

    The aim of the present investigation was to determine whether there is a net uptake of insulin-like growth factor I (IGF-I) or IGF-binding proteins (IGFBPs) by the leg after burn injury and to elucidate the regulatory role of insulin exerted on this system under in vivo conditions in burn patients. Studies were performed on nine patients after burn injury (approximately 60% body surface area). Each patient was studied twice during a continuous infusion of a carbohydrate-rich enteral diet. Blood was collected simultaneously from the femoral artery and vein for the measurement of various elements of the IGF system after 7 days of enteral diet alone (basal period) and after 7 days of the enteral diet plus the infusion of insulin (insulin period). Data from these patients were compared to values in age-matched fed healthy volunteers. During the basal period, burn patients demonstrated a significant reduction in the venous concentration of IGF-I and an increase in both IGFBP-1 and -2 compared to control values. Insulin produced a significant 15% increase in the IGF-I concentration in burn patients, but decreased the circulating levels of IGFBP-1 by 50%. The IGF-I and IGFBP-1 concentrations at the end of the insulin period were still significantly different from those in control subjects. Burn patients also exhibited a marked reduction in intact IGFBP-3 and the acid-labile subunit under basal conditions, and these alterations were not reversed by insulin. Under basal conditions, all burn patients had a positive arterio-venous (A-V) difference for IGF-I across the leg. The A-V difference was increased 50% in response to insulin. The net uptake of IGF-I by the leg was 2.4 micrograms/min under basal conditions, and as leg blood flow also tended to increase in response to insulin, IGF-I uptake was elevated more than 3-fold during the insulin period. No A-V difference across the leg was detected for IGFBP-1, -2, or -3 in burn patients. In conclusion, burn injury in humans

  15. Is it dietary insulin?

    Science.gov (United States)

    Vaarala, Outi

    2006-10-01

    In humans the primary trigger of insulin-specific immunity is a modified self-antigen, that is, dietary bovine insulin, which breaks neonatal tolerance to self-insulin. The immune response induced by bovine insulin spreads to react with human insulin. This primary immune response induced in the gut immune system is regulated by the mechanisms of oral tolerance. Genetic factors and environmental factors, such as the gut microflora, breast milk-derived factors, and enteral infections, control the development of oral tolerance. The age of host modifies the immune response to oral antigens because the permeability of the gut decreases with age and mucosal immune response, such as IgA response, develops with age. The factors that control the function of the gut immune system may either be protective from autoimmunity by supporting tolerance, or they may induce autoimmunity by abating tolerance to dietary insulin. There is accumulating evidence that the intestinal immune system is aberrant in children with type 1 diabetes (T1D). Intestinal immune activation and increased gut permeability are associated with T1D. These aberrancies may be responsible for the impaired control of tolerance to dietary insulin. Later in life, factors that activate insulin-specific immune cells derived from the gut may switch the response toward cytotoxic immunity. Viruses, which infect beta cells, may release autoantigens and potentiate their presentation by an infection-associated "danger signal." This kind of secondary immunization may cause functional changes in the dietary insulin primed immune cells, and lead to the infiltration of insulin-reactive T cells to the pancreatic islets. PMID:17130578

  16. Distinct right ventricle remodeling in response to pressure overload in the rat.

    Science.gov (United States)

    Mendes-Ferreira, P; Santos-Ribeiro, D; Adão, R; Maia-Rocha, C; Mendes-Ferreira, M; Sousa-Mendes, C; Leite-Moreira, A F; Brás-Silva, C

    2016-07-01

    Pulmonary arterial hypertension (PAH), the most serious chronic disorder of the pulmonary circulation, is characterized by pulmonary vasoconstriction and remodeling, resulting in increased afterload on the right ventricle (RV). In fact, RV function is the main determinant of prognosis in PAH. The most frequently used experimental models of PAH include monocrotaline- and chronic hypoxia-induced PAH, which primarily affect the pulmonary circulation. Alternatively, pulmonary artery banding (PAB) can be performed to achieve RV overload without affecting the pulmonary vasculature, allowing researchers to determine the RV-specific effects of their drugs/interventions. In this work, using two different degrees of pulmonary artery constriction, we characterize, in full detail, PAB-induced adaptive and maladaptive remodeling of the RV at 3 wk after PAB surgery. Our results show that application of a mild constriction resulted in adaptive hypertrophy of the RV, with preserved systolic and diastolic function, while application of a severe constriction resulted in maladaptive hypertrophy, with chamber dilation and systolic and diastolic dysfunction up to the isolated cardiomyocyte level. By applying two different degrees of constriction, we describe, for the first time, a reliable and short-duration PAB model in which RV adaptation can be distinguished at 3 wk after surgery. We characterize, in full detail, structural and functional changes of the RV in its response to moderate and severe constriction, allowing researchers to better study RV physiology and transition to dysfunction and failure, as well as to determine the effects of new therapies. PMID:27199115

  17. A fly's view of neuronal remodeling.

    Science.gov (United States)

    Yaniv, Shiri P; Schuldiner, Oren

    2016-09-01

    Developmental neuronal remodeling is a crucial step in sculpting the final and mature brain connectivity in both vertebrates and invertebrates. Remodeling includes degenerative events, such as neurite pruning, that may be followed by regeneration to form novel connections during normal development. Drosophila provides an excellent model to study both steps of remodeling since its nervous system undergoes massive and stereotypic remodeling during metamorphosis. Although pruning has been widely studied, our knowledge of the molecular and cellular mechanisms is far from complete. Our understanding of the processes underlying regrowth is even more fragmentary. In this review, we discuss recent progress by focusing on three groups of neurons that undergo stereotypic pruning and regrowth during metamorphosis, the mushroom body γ neurons, the dendritic arborization neurons and the crustacean cardioactive peptide peptidergic neurons. By comparing and contrasting the mechanisms involved in remodeling of these three neuronal types, we highlight the common themes and differences as well as raise key questions for future investigation in the field. WIREs Dev Biol 2016, 5:618-635. doi: 10.1002/wdev.241 For further resources related to this article, please visit the WIREs website. PMID:27351747

  18. The F-actin modifier villin regulates insulin granule dynamics and exocytosis downstream of islet cell autoantigen 512

    Directory of Open Access Journals (Sweden)

    Hassan Mziaut

    2016-08-01

    Conclusion: Our findings show that villin controls the size of the F-actin cages restricting SGs and, thus, regulates their dynamics and availability for exocytosis. Evidence that villin acts downstream of Ica512 also indicates that SGs directly influence the remodeling properties of the cortical actin cytoskeleton for tight control of insulin secretion.

  19. Multidetector computed tomography predictors of late ventricular remodeling and function after acute myocardial infarction

    International Nuclear Information System (INIS)

    Background: Despite advent of rapid arterial revascularization as 1st line treatment for acute myocardial infarction (AMI), incomplete restoral of flow at the microvascular level remains a problem and is associated with adverse prognosis, including pathological ventricular remodeling. We aimed to study the association between multidetector row computed tomography (MDCT) perfusion defects and ventricular remodeling post-AMI. Methods: In a prospective study, 20 patients with ST-elevation AMI, treated by primary angioplasty, underwent arterial and late phase MDCT as well as radionuclide scans to study presence, size and severity of myocardial perfusion defects. Contrast echocardiography was performed at baseline and at 4 months follow-up to evaluate changes in myocardial function and remodeling. Results: Early defects (ED), late defects (LD) and late enhancement (LE) were detected in 15, 7 and 16 patients, respectively and radionuclide defects in 15 patients. The ED area (r = 0.74), and LD area (r = 0.72), and to a lesser extent LE area (r = 0.62) correlated moderately well with SPECT summed rest score. By univariate analysis, follow-up end-systolic volume index and ejection fraction were both significantly related to ED and LD size and severity, but not to LE size or severity. By multivariate analysis, end-systolic volume index was best predicted by LD area (p < 0.05) and ejection fraction by LD enhancement ratio. Conclusions: LD size and severity on MDCT are most closely associated with pathological ventricular remodeling after AMI and may thus play a role in early identification and treatment of this condition

  20. Hepatic Shunting of Eggs and Pulmonary Vascular Remodeling in Bmpr2+/− Mice with Schistosomiasis

    Science.gov (United States)

    Soon, Elaine; Jones, Frances M.; Southwood, Mark R.; Haghighat, Leila; Toshner, Mark R.; Raine, Tim; Horan, Ian; Yang, Peiran; Moore, Stephen; Ferrer, Elisabet; Wright, Penny; Ormiston, Mark L.; White, R. James; Haight, Deborah A.; Dunne, David W.

    2015-01-01

    Rationale: Schistosomiasis is a major cause of pulmonary arterial hypertension (PAH). Mutations in the bone morphogenetic protein type-II receptor (BMPR-II) are the commonest genetic cause of PAH. Objectives: To determine whether Bmpr2+/− mice are more susceptible to schistosomiasis-induced pulmonary vascular remodeling. Methods: Wild-type (WT) and Bmpr2+/− mice were infected percutaneously with Schistosoma mansoni. At 17 weeks postinfection, right ventricular systolic pressure and liver and lung egg counts were measured. Serum, lung and liver cytokine, pulmonary vascular remodeling, and liver histology were assessed. Measurements and Main Results: By 17 weeks postinfection, there was a significant increase in pulmonary vascular remodeling in infected mice. This was greater in Bmpr2+/− mice and was associated with an increase in egg deposition and cytokine expression, which induced pulmonary arterial smooth muscle cell proliferation, in the lungs of these mice. Interestingly, Bmpr2+/− mice demonstrated dilatation of the hepatic central vein at baseline and postinfection, compared with WT. Bmpr2+/− mice also showed significant dilatation of the liver sinusoids and an increase in inflammatory cells surrounding the central hepatic vein, compared with WT. This is consistent with an increase in the transhepatic passage of eggs. Conclusions: This study has shown that levels of BMPR-II expression modify the pulmonary vascular response to chronic schistosomiasis. The likely mechanism involves the increased passage of eggs to the lungs, caused by altered diameter of the hepatic veins and sinusoids in Bmpr2+/− mice. Genetically determined differences in the remodeling of hepatic vessels may represent a new risk factor for PAH associated with schistosomiasis. PMID:26308618

  1. Multidetector computed tomography predictors of late ventricular remodeling and function after acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Lessick, Jonathan, E-mail: j_lessick@rambam.health.gov.il [Cardiology Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Technion-IIT, Haaliya Street, Haifa (Israel); Abadi, Sobhi [Medical Imaging Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Agmon, Yoram [Cardiology Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Technion-IIT, Haaliya Street, Haifa (Israel); Keidar, Zohar [Nuclear Medicine Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Technion-IIT, Haaliya Street, Haifa (Israel); Carasso, Shemi; Aronson, Doron [Cardiology Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Technion-IIT, Haaliya Street, Haifa (Israel); Ghersin, Eduard [Department of Diagnostic Radiology, University of Miami, Miller School of Medicine, Miami, FL (United States); Rispler, Shmuel [Cardiology Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Technion-IIT, Haaliya Street, Haifa (Israel); Sebbag, Anat [Cardiology Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Israel, Ora [Nuclear Medicine Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Technion-IIT, Haaliya Street, Haifa (Israel); Hammerman, Haim; Roguin, Ariel [Cardiology Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Technion-IIT, Haaliya Street, Haifa (Israel)

    2012-10-15

    Background: Despite advent of rapid arterial revascularization as 1st line treatment for acute myocardial infarction (AMI), incomplete restoral of flow at the microvascular level remains a problem and is associated with adverse prognosis, including pathological ventricular remodeling. We aimed to study the association between multidetector row computed tomography (MDCT) perfusion defects and ventricular remodeling post-AMI. Methods: In a prospective study, 20 patients with ST-elevation AMI, treated by primary angioplasty, underwent arterial and late phase MDCT as well as radionuclide scans to study presence, size and severity of myocardial perfusion defects. Contrast echocardiography was performed at baseline and at 4 months follow-up to evaluate changes in myocardial function and remodeling. Results: Early defects (ED), late defects (LD) and late enhancement (LE) were detected in 15, 7 and 16 patients, respectively and radionuclide defects in 15 patients. The ED area (r = 0.74), and LD area (r = 0.72), and to a lesser extent LE area (r = 0.62) correlated moderately well with SPECT summed rest score. By univariate analysis, follow-up end-systolic volume index and ejection fraction were both significantly related to ED and LD size and severity, but not to LE size or severity. By multivariate analysis, end-systolic volume index was best predicted by LD area (p < 0.05) and ejection fraction by LD enhancement ratio. Conclusions: LD size and severity on MDCT are most closely associated with pathological ventricular remodeling after AMI and may thus play a role in early identification and treatment of this condition.

  2. VASCULAR REMODELING AND HEART RATE VARIABILITY IN DIFFERENT ANTIHYPERTENSIVE THERAPIES

    Directory of Open Access Journals (Sweden)

    E. D. Golovanova

    2008-01-01

    Full Text Available Aim. To study the effect of the long-term antihypertensive monotherapy with indapamide (Arifon Retard, 1,5 mg/d, metoprolol tartrate (Egilok Retard, 50 mg/d and combined therapy with indapamide and perindopril (Noliprel Forte, 1 tab/d: perindopril 4 mg and indapamide 1,25 mg on pulse wave velocity (PWV, cardio-ankle vascular index (CAVI and the sympathetic system activity.Material and methods. 88 patients, aged 30-59 y.o. (32 normotensive patients, 56 with arterial hypertension [HT] of 1-2 grades were examined. Biological age (BA was determined by the linear regression and the vascular wall age (VWA was estimated with the use of volume sphygmography (“VaSera-1000”, “Fucuda Denshi”, Japan. 39 patients with HT were randomized into 3 parallel groups with studied therapies lasted for 6 months. PWV, CAVI of the vessels of elastic, muscular and mixed types, blood pressure, measured in upper and lower extremities and heart rate variability (HRV were determined before and at the end of the therapies.Results. BA and VWA were elevated in all of patients with HT as compared with normotensive patients. The reduction in PWV and CAVI of the vessels of elastic and mixed types, HRV increase were found in patients with Arifon Retard monotherapy. Monotherapy with metoprolol significantly improved HVR without any influence on the vascular remodeling. Noliprel Forte significantly decreased in blood pressure in the upper and lower extremities, PWV and CAVI of the vessels of all types, decreased in VWA and increased in parasympathetic drive.Conclusion. Long-term therapy with Arifon Retard and Noliprel Forte resulted in decrease in vascular remodeling and increase in HRV simultaneously with significant antihypertensive effect in patients with HT. Metoprolol low doses therapy resulted in normalization of autonomic drive independently on antihypertensive action.

  3. Adenoviral short hairpin RNA targeting phosphodiesterase 5 attenuates cardiac remodeling and cardiac dysfunction following myocardial infarction in mice

    Institute of Scientific and Technical Information of China (English)

    张健

    2014-01-01

    Objective To observe the impact of PDE5shRNA on cardiac remodeling and heart function following myocardial infarction in mice.Methods Myocardial infarction(MI)was induced in mice by left coronary artery ligation.Mice were randomly assigned to sham operation group(n=6),PDE5shRNA group(n=12),common adenovirus group(n=15)and DMEM group(n=8).Four weeks post-MI,the survival rate was evaluated.

  4. Extracellular Matrix Remodeling of the Umbilical Cord in Pre-eclampsia as a Risk Factor for Fetal Hypertension

    OpenAIRE

    Lech Romanowicz; Zofia Galewska

    2011-01-01

    The human umbilical cord forms a connection between the placenta and the foetus. It is composed of two arteries and one vein surrounded by Wharton's jelly. Pre-eclampsia is accompanied by extensive remodeling of extracellular matrix of umbilical cord. Matrix metalloproteinases (MMPs) are engaged in degradation of extracellular matrix proteins and activation/inactivation of certain cytokines and enzymes. These enzymes will probably play a central role in the release of matrix-embedded cytokine...

  5. HIF-2α-mediated induction of pulmonary thrombospondin-1 contributes to hypoxia-driven vascular remodelling and vasoconstriction

    OpenAIRE

    Labrousse-Arias, David; Castillo-González, Raquel; Rogers, Natasha M.; Torres-Capelli, Mar; Barreira, Bianca; Aragonés, Julián; Cogolludo, Ángel; Isenberg, Jeffrey S.; Calzada, María J.

    2015-01-01

    Aims Hypoxic conditions stimulate pulmonary vasoconstriction and vascular remodelling, both pathognomonic changes in pulmonary arterial hypertension (PAH). The secreted protein thrombospondin-1 (TSP1) is involved in the maintenance of lung homeostasis. New work identified a role for TSP1 in promoting PAH. Nonetheless, it is largely unknown how hypoxia regulates TSP1 in the lung and whether this contributes to pathological events during PAH. Methods and results In cell and animal experiments, ...

  6. Drosophila insulin degrading enzyme and rat skeletal muscle insulin protease cleave insulin at similar sites

    International Nuclear Information System (INIS)

    Insulin degradation is an integral part of the cellular action of insulin. Recent evidence suggests that the enzyme insulin protease is involved in the degradation of insulin in mammalian tissues. Drosophila, which has insulin-like hormones and insulin receptor homologues, also expresses an insulin degrading enzyme with properties that are very similar to those of mammalian insulin protease. In the present study, the insulin cleavage products generated by the Drosophila insulin degrading enzyme were identified and compared with the products generated by the mammalian insulin protease. Both purified enzymes were incubated with porcine insulin specifically labeled with 125I on either the A19 or B26 position, and the degradation products were analyzed by HPLC before and after sulfitolysis. Isolation and sequencing of the cleavage products indicated that both enzymes cleave the A chain of intact insulin at identical sites between residues A13 and A14 and A14 and A15. These results demonstrate that all the insulin cleavage sites generated by the Drosopohila insulin degrading enzyme are shared in common with the mammalian insulin protease. These data support the hypothesis that there is evolutionary conservation of the insulin degrading enzyme and further suggest that this enzyme plays an important role in cellular function

  7. Insulin Resistance and Hypertension

    Institute of Scientific and Technical Information of China (English)

    张建华; 张春秀

    2002-01-01

    Summary: The insulin sensitivity in hypertensive patients with normal glucose tolerance (NGT),impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM) and the insulin resistance(IR) under the disorder of glucose metabolism and hypertension were studied. By glucose toler-ance test and insulin release test, insulin sensitivity index (ISI) and the ratio of area under glucosetolerance curve (AUCG) to area under insulin release curve (AUC1) were calculated and analyzed.The results showed that ISI was decreased to varying degrees in the patients with hypertension,the mildest in the group of NGT with hypertension, followed by the group of IGT without hyper-tension, the group of IGT with hypertension and DM (P=0). There was very significant differ-ence in the ratio of AUCG/AUC1 between the hypertensive patients with NGT and controls (P=0). It was concluded that a significant IR existed during the development of IGT both in hyperten-sion and nonhypertension. The increase of total insulin secretion (AUC1) was associated with non-hypertension simultaneously. IR of the hypertensive patients even existed in NGT and was wors-ened with the deterioration of glucose metabolism disorder, but the AUC1 in the HT groupchanged slightly. A relative deficiency of insulin secretion or dysfunction of β-cell of islet existed inIGT and DM of the hypertensive patients.

  8. A superactive insulin: [B10-aspartic acid]insulin(human).

    OpenAIRE

    Schwartz, G P; Burke, G. T.; Katsoyannis, P G

    1987-01-01

    The genetic basis for a case of familial hyperproinsulinemia has been elucidated recently. It involves a single point mutation in the proinsulin gene resulting in the substitution of aspartic acid for histidine-10 of the B chain of insulin. We have synthesized a human insulin analogue, [AspB10]insulin, corresponding to the mutant proinsulin and evaluated its biological activity. [AspB10]Insulin displayed a binding affinity to insulin receptors in rat liver plasma membranes that was 534 +/- 14...

  9. Aldosterone-Induced Vascular Remodeling and Endothelial Dysfunction Require Functional Angiotensin Type 1a Receptors.

    Science.gov (United States)

    Briet, Marie; Barhoumi, Tlili; Mian, Muhammad Oneeb Rehman; Coelho, Suellen C; Ouerd, Sofiane; Rautureau, Yohann; Coffman, Thomas M; Paradis, Pierre; Schiffrin, Ernesto L

    2016-05-01

    We investigated the role of angiotensin type 1a receptors (AGTR1a) in vascular injury induced by aldosterone activation of mineralocorticoid receptors inAgtr1a(-/-)and wild-type (WT) mice infused with aldosterone for 14 days while receiving 1% NaCl in drinking water. Aldosterone increased systolic blood pressure (BP) by ≈30 mm Hg in WT mice and ≈50 mm Hg inAgtr1a(-/-)mice. Aldosterone induced aortic and small artery remodeling, impaired endothelium-dependent relaxation in WT mice, and enhanced fibronectin and collagen deposition and vascular inflammation. None of these vascular effects were observed inAgtr1a(-/-)mice. Aldosterone effects were prevented by the AGTR1 antagonist losartan in WT mice. In contrast to aldosterone, norepinephrine caused similar BP increase and mesenteric artery remodeling in WT andAgtr1a(-/-)mice.Agtr1a(-/-)mice infused with aldosterone did not increase sodium excretion in response to a sodium chloride challenge, suggesting that sodium retention could contribute to the exaggerated BP rise induced by aldosterone.Agtr1a(-/-)mice had decreased mesenteric artery expression of the calcium-activated potassium channelKcnmb1, which may enhance myogenic tone and together with sodium retention, exacerbate BP responses to aldosterone/salt inAgtr1a(-/-)mice. We conclude that although aldosterone activation of mineralocorticoid receptors raises BP more inAgtr1a(-/-)mice, AGTR1a is required for mineralocorticoid receptor stimulation to induce vascular remodeling and inflammation and endothelial dysfunction. PMID:27045029

  10. KLF5 mediates vascular remodeling via HIF-1α in hypoxic pulmonary hypertension.

    Science.gov (United States)

    Li, Xiaochen; He, Yuanzhou; Xu, Yongjian; Huang, Xiaomin; Liu, Jin; Xie, Min; Liu, Xiansheng

    2016-02-15

    Hypoxic pulmonary hypertension (HPH) is characterized by active vasoconstriction and profound vascular remodeling. KLF5, a zinc-finger transcription factor, is involved in the excessive proliferation and apoptotic resistance phenotype associated with monocrotaline-induced pulmonary hypertension. However, the molecular mechanisms of KLF5-mediated pathogenesis of HPH are largely undefined. Adult male Sprague-Dawley rats were exposed to normoxia or hypoxia (10% O2) for 4 wk. Hypoxic rats developed pulmonary arterial remodeling and right ventricular hypertrophy with significantly increased right ventricular systolic pressure. The levels of KLF5 and hypoxia-inducible factor-1α (HIF-1α) were upregulated in distal pulmonary arterial smooth muscle from hypoxic rats. The knockdown of KLF5 via short-hairpin RNA attenuated chronic hypoxia-induced hemodynamic and histological changes in rats. The silencing of either KLF5 or HIF-1α prevented hypoxia-induced (5%) proliferation and migration and promoted apoptosis in human pulmonary artery smooth muscle cells. KLF5 was immunoprecipitated with HIF-1α under hypoxia and acted as an upstream regulator of HIF-1α. The cell cycle regulators cyclin B1 and cyclin D1 and apoptosis-related proteins including bax, bcl-2, survivin, caspase-3, and caspase-9, were involved in the regulation of KLF5/HIF-1α-mediated cell survival. This study demonstrated that KLF5 plays a crucial role in hypoxia-induced vascular remodeling in an HIF-1α-dependent manner and provided a better understanding of the pathogenesis of HPH. PMID:26702149

  11. Why do anti-inflammatory therapies fail to improve insulin sensitivity?

    Institute of Scientific and Technical Information of China (English)

    Zhan-guo GAO; Jian-ping YE

    2012-01-01

    Chronic inflammation occurs in obese conditions in both humans and animals.It also contributes to the pathogenesis of type 2 diabetes (T2D) through insulin resistance,a status in which the body loses its ability to respond to insulin.Inflammation impairs insulin signaling through the functional inhibition of IRS-1 and PPARy.Insulin sensitizers (such as rosiglitazone and pioglitazone) inhibit inflammation while improving insulin sensitivity.Therefore,anti-inflammatory agents have been suggested as a treatment strategy for insulin resistance.This strategy has been tested in laboratory studies and clinical trials for more than 10 years; however,no significant progress has been made in any of the model systems.This status has led us to re-evaluate the biological significance of chronic inflammation in obesity.Recent studies have consistently asserted that obesity-associated inflammation helps to maintain insulin sensitivity.Inflammation stimulates local adipose tissue remodeling and promotes systemic energy expenditure.We propose that these beneficial activities of inflammation provide an underlying mechanism for the failure of anti-infiammatory therapy in the treatment of insulin resistance.Current literature will be reviewed in this article to present evidence that supports this viewpoint.

  12. Characterization of right ventricular remodeling and failure in a chronic pulmonary hypertension model

    Science.gov (United States)

    Ishikawa, Kiyotake; Hadri, Lahouaria; Santos-Gallego, Carlos; Fish, Kenneth; Hammoudi, Nadjib; Chaanine, Antoine; Torquato, Samantha; Naim, Charbel; Ibanez, Borja; Pereda, Daniel; García-Alvarez, Ana; Fuster, Valentin; Sengupta, Partho P.; Leopold, Jane A.; Hajjar, Roger J.

    2014-01-01

    In pulmonary hypertension (PH), right ventricular (RV) dysfunction and failure is the main determinant of a poor prognosis. We aimed to characterize RV structural and functional differences during adaptive RV remodeling and progression to RV failure in a large animal model of chronic PH. Postcapillary PH was created surgically in swine (n = 21). After an 8- to 14-wk follow-up, two groups were identified based on the development of overt heart failure (HF): PH-NF (nonfailing, n = 12) and PH-HF (n = 8). In both groups, invasive hemodynamics, pressure-volume relationships, and echocardiography confirmed a significant increase in pulmonary pressures and vascular resistance consistent with PH. Histological analysis also demonstrated distal pulmonary arterial (PA) remodeling in both groups. Diastolic dysfunction, defined by a steeper RV end-diastolic pressure-volume relationship and longitudinal strain, was found in the absence of HF as an early marker of RV remodeling. RV contractility was increased in both groups, and RV-PA coupling was preserved in PH-NF animals but impaired in the PH-HF group. RV hypertrophy was present in PH-HF, although there was evidence of increased RV fibrosis in both PH groups. In the PH-HF group, RV sarcoplasmic reticulum Ca2+-ATPase2a expression was decreased, and endoplasmic reticulum stress was increased. Aldosterone levels were also elevated in PH-HF. Thus, in the swine pulmonary vein banding model of chronic postcapillary PH, RV remodeling occurs at the structural, histological, and molecular level. Diastolic dysfunction and fibrosis are present in adaptive RV remodeling, whereas the onset of RV failure is associated with RV-PA uncoupling, defective calcium handling, and hyperaldosteronism. PMID:25158063

  13. Insulin glulisine: insulin receptor signaling characteristics in vivo.

    Science.gov (United States)

    Hennige, Anita M; Lehmann, Rainer; Weigert, Cora; Moeschel, Klaus; Schäuble, Myriam; Metzinger, Elisabeth; Lammers, Reiner; Häring, Hans-Ulrich

    2005-02-01

    In recent years, recombinant DNA technology has been used to design insulin molecules that overcome the limitations of regular insulin in mealtime supplementation. However, safety issues have been raised with these alternatives, as the alteration of the three-dimensional structure may alter the interaction with the insulin and/or IGF-I receptors and therefore lead to the activation of alternate metabolic as well as mitogenic signaling pathways. It is therefore essential to carefully study acute and long-term effects in a preclinical state, as insulin therapy is meant to be a lifelong treatment. In this study, we determined in vivo the insulin receptor signaling characteristics activated by insulin glulisine (Lys(B3), Glu(B29)) at the level of insulin receptor phosphorylation, insulin receptor substrate phosphorylation, and downstream signaling elements such as phosphatidylinositol (PI) 3-kinase, AKT, and mitogen-activated protein kinase. C57BL/6 mice were injected with insulin glulisine or regular insulin and Western blot analysis was performed for liver and muscle tissue. The extent and time course of insulin receptor phosphorylation and activation of downstream signaling elements after insulin glulisine treatment was similar to that of human regular insulin in vivo. Moreover, insulin signaling in hypothalamic tissue determined by PI 3-kinase activity was comparable. Therefore, insulin glulisine may be a useful tool for diabetes treatment. PMID:15677493

  14. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

    Samir Bhattacharya; Debleena Dey; Sib Sankar Roy

    2007-03-01

    Free fatty acids are known to play a key role in promoting loss of insulin sensitivity, thereby causing insulin resistance and type 2 diabetes. However, the underlying mechanism involved is still unclear. In searching for the cause of the mechanism, it has been found that palmitate inhibits insulin receptor (IR) gene expression, leading to a reduced amount of IR protein in insulin target cells. PDK1-independent phosphorylation of PKCε causes this reduction in insulin receptor gene expression. One of the pathways through which fatty acid can induce insulin resistance in insulin target cells is suggested by these studies. We provide an overview of this important area, emphasizing the current status.

  15. Biomechanical Remodeling of the Diabetic Gastrointestinal Tract

    DEFF Research Database (Denmark)

    Zhao, Jingbo; Liao, Donghua; Yang, Jian;

    2010-01-01

    several years, several studies demonstrated that experimental diabetes induces GI morphological and biomechanical remodeling. Following the development of diabetes, the GI wall becomes thicker and the stiffness of the GI wall increases in a time-dependent manner. It is well known that mechanosensitive...... the biomechanical environment of the mechanosensitive nerve endings, therefore, the structure as well as the tension, stress and strain distribution in the GI wall is important for the sensory and motor function. Biomechanical remodeling of diabetic GI tract including alterations of residual strain and increase...

  16. Insulin inhalation: NN 1998.

    Science.gov (United States)

    2004-01-01

    Aradigm Corporation has developed an inhaled form of insulin using its proprietary AERx drug delivery system. The system uses liquid insulin that is converted into an aerosol containing very small particles (1-3 micro in diameter), and an electronic device suitable for either the rapid transfer of molecules of insulin into the bloodstream or localised delivery within the lung. The AERx insulin Diabetes Management System (iDMS), AERx iDMS, instructs the user on breathing technique to achieve the best results. Aradigm Corporation and Novo Nordisk have signed an agreement to jointly develop a pulmonary delivery system for insulin [AERx iDMS, NN 1998]. Under the terms of the agreement, Novo Nordisk has exclusive rights for worldwide marketing of any products resulting from the development programme. Aradigm Corporation will initially manufacture the product covered by the agreement, and in return will receive a share of the overall gross profits from Novo Nordisk's sales. Novo Nordisk will cover all development costs incurred by Aradigm Corporation while both parties will co-fund final development of the AERx device. Both companies will explore the possibilities of the AERx platform to deliver other compounds for the regulation of blood glucose levels. Additionally, the agreement gives Novo Nordisk an option to develop the technology for delivery of agents outside the diabetes area. In April 2001, Aradigm Corporation received a milestone payment from Novo Nordisk related to the completion of certain clinical and product development stages of the AERx drug delivery system. Profil, a CRO in Germany, is cooperating with Aradigm and Novo Nordisk in the development of inhaled insulin. Aradigm and Novo Nordisk initiated a pivotal phase III study with inhaled insulin formulation in September 2002. This 24-month, 300-patient trial is evaluating inhaled insulin in comparison with insulin aspart. Both medications will be given three times daily before meals in addition to basal

  17. IKKβ Is Essential for Adipocyte Survival and Adaptive Adipose Remodeling in Obesity.

    Science.gov (United States)

    Park, Se-Hyung; Liu, Zun; Sui, Yipeng; Helsley, Robert N; Zhu, Beibei; Powell, David K; Kern, Philip A; Zhou, Changcheng

    2016-06-01

    IκB kinase β (IKKβ), a central coordinator of inflammatory responses through activation of nuclear factor-κB (NF-κB), has been implicated as a critical molecular link between inflammation and metabolic disorders; however, the role of adipocyte IKKβ in obesity and related metabolic disorders remains elusive. Here we report an essential role of IKKβ in the regulation of adipose remodeling and adipocyte survival in diet-induced obesity. Targeted deletion of IKKβ in adipocytes does not affect body weight, food intake, and energy expenditure but results in an exaggerated diabetic phenotype when challenged with a high-fat diet (HFD). IKKβ-deficient mice have multiple histopathologies in visceral adipose tissue, including increased adipocyte death, amplified macrophage infiltration, and defective adaptive adipose remodeling. Deficiency of IKKβ also leads to increased adipose lipolysis, elevated plasma free fatty acid (FFA) levels, and impaired insulin signaling. Mechanistic studies demonstrated that IKKβ is a key adipocyte survival factor and that IKKβ protects murine and human adipocytes from HFD- or FFA-elicited cell death through NF-κB-dependent upregulation of antiapoptotic proteins and NF-κB-independent inactivation of proapoptotic BAD protein. Our findings establish IKKβ as critical for adipocyte survival and adaptive adipose remodeling in obesity. PMID:26993069

  18. Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Zinman, Bernard; Philis-Tsimikas, Athena; Cariou, Bertrand;

    2012-01-01

    To compare ultra-long-acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs).......To compare ultra-long-acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs)....

  19. Insulin Resistance and Prediabetes

    Science.gov (United States)

    ... use it for energy. Insulin's Role in Blood Glucose Control When blood glucose levels rise after a meal, ... also helps a person lose weight control blood glucose levels control blood pressure control cholesterol levels People in the ...

  20. Insulin Resistance and Prediabetes

    Science.gov (United States)

    ... Research Training & Career Development Grant programs for students, postdocs, and faculty Research at NIDDK Labs, faculty, and ... it for energy. Insulin's Role in Blood Glucose Control When blood glucose levels rise after a meal, ...

  1. Insulin Augmentation of Glucose-Stimulated Insulin Secretion Is Impaired in Insulin-Resistant Humans

    OpenAIRE

    Halperin, Florencia; Lopez, Ximena; Manning, Raquel; Kahn, C. Ronald; Kulkarni, Rohit Narayan; Goldfine, Allison Braunwald

    2012-01-01

    Type 2 diabetes (T2D) is characterized by insulin resistance and pancreatic β-cell dysfunction, the latter possibly caused by a defect in insulin signaling in β-cells. We hypothesized that insulin’s effect to potentiate glucose-stimulated insulin secretion (GSIS) would be diminished in insulin-resistant persons. To evaluate the effect of insulin to modulate GSIS in insulin-resistant compared with insulin-sensitive subjects, 10 participants with impaired glucose tolerance (IGT), 11 with T2D, a...

  2. Insulin absorption and subcutaneous blood flow in normal subjects during insulin-induced hypoglycemia

    International Nuclear Information System (INIS)

    We studied the effects of insulin-induced hypoglycemia on the absorption of 10 U 125I-labeled soluble human insulin injected sc in the thigh in 10 normal subjects. The disappearance of 125I from the injection site was followed by external gamma-counting. Subcutaneous blood flow (ATBF) was measured concomitantly with the 133Xe washout technique. The plasma glucose nadir [mean, 2.0 +/- 0.1 (+/- SE) mmol/L] occurred at 33 +/- 3 min and resulted in maximal arterial plasma epinephrine concentrations of approximately 6 nmol/L. From 30 min before to 60 min after the glucose nadir the [125I]insulin absorption rate was depressed compared to that during normoglycemia. The first order disappearance rate constants were reduced by approximately 50% (P less than 0.01) during the first 30-min interval after the glucose nadir. During the same period ATBF increased by 100% (P less than 0.05). The results suggest that in normal subjects the absorption of soluble insulin from a sc depot is depressed in connection with hypoglycemia, despite considerably elevated ATBF

  3. Insulin absorption and subcutaneous blood flow in normal subjects during insulin-induced hypoglycemia

    Energy Technology Data Exchange (ETDEWEB)

    Fernqvist-Forbes, E.; Linde, B.; Gunnarsson, R.

    1988-09-01

    We studied the effects of insulin-induced hypoglycemia on the absorption of 10 U /sup 125/I-labeled soluble human insulin injected sc in the thigh in 10 normal subjects. The disappearance of /sup 125/I from the injection site was followed by external gamma-counting. Subcutaneous blood flow (ATBF) was measured concomitantly with the 133Xe washout technique. The plasma glucose nadir (mean, 2.0 +/- 0.1 (+/- SE) mmol/L) occurred at 33 +/- 3 min and resulted in maximal arterial plasma epinephrine concentrations of approximately 6 nmol/L. From 30 min before to 60 min after the glucose nadir the (/sup 125/I)insulin absorption rate was depressed compared to that during normoglycemia. The first order disappearance rate constants were reduced by approximately 50% (P less than 0.01) during the first 30-min interval after the glucose nadir. During the same period ATBF increased by 100% (P less than 0.05). The results suggest that in normal subjects the absorption of soluble insulin from a sc depot is depressed in connection with hypoglycemia, despite considerably elevated ATBF.

  4. Insulin allergy treated with human insulin (recombinant DNA).

    Science.gov (United States)

    De Leeuw, I; Delvigne, C; Bekaert, J

    1982-01-01

    Two insulin-dependent diabetic subjects treated with pork and beef insulin during a period of 6 mo developed severe local reactions. Both patients had an important allergic history (asthma, urticaria, drug reactions, rhinitis). Skin-testing revealed type I allergy to beef and pork insulin. Specific IgE-insulin binding was demonstrated with both insulins. After negative skin testing with NPH Lilly human insulin (recombinant DNA), treatment was started with this compound and remained successful during a period of 6-9 mo. In one patient a local reaction occurred when regular human insulin (recombinant DNA) was added to NPH in order to obtain better control. Skin testing with regular human insulin was positive, but not with NPH human insulin alone. The mechanism of this phenomenon remains unsolved. PMID:6765530

  5. Carotid Artery Disease

    Science.gov (United States)

    ... brain with blood. If you have carotid artery disease, the arteries become narrow, usually because of atherosclerosis. ... one of the causes of stroke. Carotid artery disease often does not cause symptoms, but there are ...

  6. Mesenteric artery ischemia

    Science.gov (United States)

    Mesenteric artery ischemia occurs when there is a narrowing or blockage of one or more of the three major arteries that ... that supply blood to the intestine causes mesenteric ischemia. The arteries that supply blood to the intestines ...

  7. Etiopathogenesis of Insulin Autoimmunity

    Directory of Open Access Journals (Sweden)

    Norio Kanatsuna

    2012-01-01

    Full Text Available Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (proinsulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining lymphnodes. Recent data on proinsulin peptide binding to type 1 diabetes-associated HLA-DQ2 and -DQ8 is reviewed and illustrated by molecular modeling. The importance of the cellular immune reaction involving cytotoxic CD8-positive T cells to kill beta cells through Class I MHC is discussed along with speculations of the possible role of B lymphocytes in presenting the proinsulin autoantigen over and over again through insulin-carrying insulin autoantibodies. In contrast to autoantibodies against other islet autoantigens such as GAD65, IA-2, and ZnT8 transporters, it has not been possible yet to standardize the insulin autoantibody test. As islet autoantibodies predict type 1 diabetes, it is imperative to clarify the mechanisms of insulin autoimmunity.

  8. Conformational Dynamics of Insulin

    Directory of Open Access Journals (Sweden)

    Qing-xin eHua

    2011-10-01

    Full Text Available We have exploited a prandial insulin analogue (insulin lispro, the active component of Humalog®; Eli Lilly and Co. to elucidate the underlying structure and dynamics of insulin as a monomer in solution. Whereas NMR-based modeling recapitulates structural relationships of insulin crystals (T-state protomers, dynamic anomalies are revealed by amide-proton exchange kinetics in D2O. Surprisingly, the majority of hydrogen bonds observed in crystal structures are only transiently maintained in solution, including key T-state-specific inter-chain contacts. Long-lived hydrogen bonds (as defined by global exchange kinetics exist only at a subset of four -helical sites (two per chain flanking an internal disulfide bridge (cystine A20-B19; these sites map within the proposed folding nucleus of proinsulin. The anomalous flexibility of insulin otherwise spans its active surface and may facilitate receptor binding. Because conformational fluctuations promote the degradation of pharmaceutical formulations, we envisage that dynamic re-engineering of insulin may enable design of ultra-stable formulations for humanitarian use in the developing world.

  9. Performance Requirements on Remodeling Apartment Housing and TOPSIS Evaluation

    OpenAIRE

    Jaeho Cho; Jaeyoul Chun

    2015-01-01

    Functional improvement needed in remodeling projects is determined by users in a complex manner since remodeling projects require performance improvement against deterioration. This study defines fundamental Remodeling Performance Criteria (RPC) for apartment housing by referring to performance criteria of both domestic and international performance-related systems. In this case study, performance evaluation of Construction Element Method (CEM) for remodeling projects was conducted based on R...

  10. Insulin degludec and insulin aspart: novel insulins for the management of diabetes mellitus

    OpenAIRE

    Atkin, Stephen; Javed, Zeeshan; Fulcher, Gregory

    2015-01-01

    Patients with type 2 diabetes mellitus require insulin as disease progresses to attain or maintain glycaemic targets. Basal insulin is commonly prescribed initially, alone or with one or more rapid-acting prandial insulin doses, to limit mealtime glucose excursions (a basal–bolus regimen). Both patients and physicians must balance the advantages of improved glycaemic control with the risk of hypoglycaemia and increasing regimen complexity. The rapid-acting insulin analogues (insulin aspart, i...

  11. New predictive model for monitoring bone remodeling

    Czech Academy of Sciences Publication Activity Database

    Bougherara, H.; Klika, Václav; Maršík, František; Mařík, I.; Yahia, L.H.

    95A, č. 1 (2010), s. 9-24. ISSN 1549-3296 R&D Projects: GA ČR GA106/03/1073; GA ČR(CZ) GA106/03/0958 Institutional research plan: CEZ:AV0Z20760514 Keywords : bone remodeling * open system thermodynamics * bone biochemistry Subject RIV: BJ - Thermodynamics Impact factor: 3.044, year: 2010

  12. Link between vitamin D and airway remodeling

    Directory of Open Access Journals (Sweden)

    Berraies A

    2014-04-01

    Full Text Available Anissa Berraies, Kamel Hamzaoui, Agnes HamzaouiPediatric Respiratory Diseases Department, Abderrahmen Mami Hospital, Ariana, and Research Unit 12SP15 Tunis El Manar University, Tunis, TunisiaAbstract: In the last decade, many epidemiologic studies have investigated the link between vitamin D deficiency and asthma. Most studies have shown that vitamin D deficiency increases the risk of asthma and allergies. Low levels of vitamin D have been associated with asthma severity and loss of control, together with recurrent exacerbations. Remodeling is an early event in asthma described as a consequence of production of mediators and growth factors by inflammatory and resident bronchial cells. Consequently, lung function is altered, with a decrease in forced expiratory volume in one second and exacerbated airway hyperresponsiveness. Subepithelial fibrosis and airway smooth muscle cell hypertrophy are typical features of structural changes in the airways. In animal models, vitamin D deficiency enhances inflammation and bronchial anomalies. In severe asthma of childhood, major remodeling is observed in patients with low vitamin D levels. Conversely, the antifibrotic and antiproliferative effects of vitamin D in smooth muscle cells have been described in several experiments. In this review, we briefly summarize the current knowledge regarding the relationship between vitamin D and asthma, and focus on its effect on airway remodeling and its potential therapeutic impact for asthma.Keywords: vitamin D, asthma, airway remodeling, airway smooth muscle, supplementation

  13. Interleukin-20 promotes airway remodeling in asthma.

    Science.gov (United States)

    Gong, Wenbin; Wang, Xin; Zhang, Yuguo; Hao, Junqing; Xing, Chunyan; Chu, Qi; Wang, Guicheng; Zhao, Jiping; Wang, Junfei; Dong, Qian; Liu, Tian; Zhang, Yuanyuan; Dong, Liang

    2014-12-01

    Previous studies have demonstrated that interleukin-20 (IL-20) is a pro-inflammatory cytokine, and it has been implicated in psoriasis, lupus nephritis, rheumatoid arthritis, atherosclerosis, and ulcerative colitis. Little is known about the effects of IL-20 in airway remodeling in asthma. The aim of our study was to demonstrate the function of IL-20 in airway remodeling in asthma. To identify the expression of IL-20 and its receptor, IL-20R1/IL-20R2, in the airway epithelium in bronchial tissues, bronchial biopsy specimens were collected from patients and mice with asthma and healthy subjects and stained with specific antibodies. To characterize the effects of IL-20 in asthmatic airway remodeling, we silenced and stimulated IL-20 in cell lines isolated from mice by shRNA and recombinant protein approaches, respectively, and detected the expression of α-SMA and FN-1 by Western blot analysis. First, overexpression of IL-20 and its receptor, IL-20R1/IL-20R2, was detected in the airway epithelium collected from patients and mice with asthma. Second, IL-20 increased the expression of fibronectin-1 and α-SMA, and silencing of IL-20 in mouse lung epithelial (MLE)-12 cells decreased the expression of fibronectin-1 and α-SMA. IL-20 may be a critical cytokine in airway remodeling in asthma. This study indicates that targeting IL-20 and/or its receptors may be a new therapeutic strategy for asthma. PMID:25028099

  14. Connexin Remodeling Contributes to Atrial Fibrillation

    OpenAIRE

    Michelle M Jennings; J Kevin Donahue

    2013-01-01

    Atrial fibrillation significantly contributes to mortality and morbidity through increased risk of stroke, heart failure and myocardial infarcts. Investigations of mechanisms responsible for the development and maintenance of atrial fibrillation have highlighted the importance of gap junctional remodeling. Connexins 40 and 43, the major atrial gap junctional proteins, undergo considerable alterations in expression and localization in atrial fibrillation, creating an environment conducive to s...

  15. Remodelling of flash furnace for coal firing

    Energy Technology Data Exchange (ETDEWEB)

    Kawai, Z.

    1982-05-01

    The Chichiku Cement Co. has succeeded in re-converting all its cement plants from oil to coal firing system with no impairment at all to production rate or to unit energy consumption. The reconversion wea achieved by remodelling four of its five principal kilns from a system of suspension preheater with calciner to the C-SF kiln system.

  16. MYOCARDIAL REMODELING IN ISCHEMIC HEART DISEASE

    Directory of Open Access Journals (Sweden)

    A. N. Zakirova

    2016-01-01

    Full Text Available Aim. To study the myocardial remodeling features in patients with stable angina depending on disease severity and experienced myocardial infarction (MI.Material and methods. 148 male patients with stable angina were examined and randomized into 3 groups (G1-G3. 52 patients of G1 had angina of I-II functional class (FC. 49 patients of G2 had angina of III FC, and 47 patients of G3 had angina of IV FC. History of MI had 79,5, 87.2 and 92.6% of patients in G1, G2 and G3 respectively. 35 healthy men were included into control group. Coronarography, bicycle ergometry and 24-hour ECG monitoring was performed. Left ventricular (LV function and remodeling was assessed with echocardiography.Results. G3 patients had LV eccentric hypertrophy as a result of postinfarction cardiosclerosis which accompanied with LV systolic dysfunction, a myocardial stress increasing and LV spherification. G1 patients had no any significant disorders of LV systolic function.Conclusion. Severe ischemic heart disease is associated with a dysadaptive remodeling unlike mild ischemic heart disease, which is associated with an adaptive myocardial remodeling.

  17. Re-Modelling as De-Professionalisation

    Science.gov (United States)

    Thompson, Meryl

    2006-01-01

    The article sets out the consequences of the British Government's remodelling agenda and its emphasis on less demarcation, for the professional status of teachers in England. It describes how the National Agreement on Raising Standards and Tackling Workload, reached between five of the six trade unions for teachers and headteachers paves the way…

  18. Association of adiponectin gene polymorphism with adiponectin levels and risk for insulin resistance syndrome

    OpenAIRE

    Jai Prakash; Balraj Mittal; Shally Awasthi; Neena Srivastava

    2015-01-01

    Background: Adiponectin is an abundant adipose tissue-derived protein with anti-atherogenic, anti-inflammatory and antidiabetic properties. Plasma adiponectin levels are decreased in obesity, type 2 diabetes, and coronary artery disease and low adiponectin levels also predict insulin resistance (IR). Methods: Case-control study in which 642 male and female subjects were participated from the North Indian population. Lipid, insulin, leptin and adiponectin level were estimated using standar...

  19. Brachytherapy in coronary artery disease

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ho Chun [Chonnam National University Medicine School, Gwangju (Korea, Republic of)

    2006-04-15

    Coronary artery disease is a leading cause of morbidity and mortality across the world. Percutaneous coronary intervention has become the major technique of revascularization. However, restenosis remains a major limitation of this procedure. Recently the need for repeat intervention due to restenosis, the most vexing long-term failure of percutaneous coronary intervention, has been significantly reduced owing to the introduction to two major advances, intracoronary brachytherapy and the drug-eluting stents, intracoronary brachytherapy has been employed in recent years to prevent restenosis lesions with effective results, principally in in-stent restenosis. Restenosis is generally considered as an excessive form of normal wound healing divided up in processes: elastic recoil, neointimal hyperplasia, and negative vascular remodeling. Restenosis has previously been regarded as a proliferative process in which neointimal thickening, mediated by a cascade of inflammatory mediators and other factors, is the key factor. Ionizing radiation has been shown to decrease the proliferative response to injury in animal models of restenosis. Subsequently, several randomized, double-blind trials have demonstrated that intracoronary brachytherapy can reduce the rates to both angiographic restenosis and clinical event rates in patients undergoing percutaneous coronary intervention for in-stent restenosis. Some problems, such as late thrombosis and edge restenosis, have been identified as limiting factors of this technique. Brachytherapy is a promising method of preventing and treating coronary artery restenosis.

  20. Loss of alveolar membrane diffusing capacity and pulmonary capillary blood volume in pulmonary arterial hypertension

    OpenAIRE

    Farha Samar; Laskowski Daniel; George Deepa; Park Margaret M; Tang WH Wilson; Dweik Raed A; Erzurum Serpil C

    2013-01-01

    Abstract Background Reduced gas transfer in patients with pulmonary arterial hypertension (PAH) is traditionally attributed to remodeling and progressive loss of pulmonary arterial vasculature that results in decreased capillary blood volume available for gas exchange. Methods We tested this hypothesis by determination of lung diffusing capacity (DL) and its components, the alveolar capillary membrane diffusing capacity (Dm) and lung capillary blood volume (Vc) in 28 individuals with PAH in c...

  1. Evidence for cell fusion is absent in vascular lesions associated with pulmonary arterial hypertension

    OpenAIRE

    Majka, S. M.; M. Skokan; Wheeler, L; Harral, J.; Gladson, S.; Burnham, E.; J. E. Loyd; Stenmark, K R; Varella-Garcia, M; West, J.

    2008-01-01

    Pulmonary arterial hypertension (PAH) is a fatal disease associated with severe remodeling of the large and small pulmonary arteries. Increased accumulation of inflammatory cells and apoptosis-resistant cells are contributing factors. Proliferative apoptosis-resistant cells expressing CD133 are increased in the circulation of PAH patients. Circulating cells can contribute to tissue repair via cell fusion and heterokaryon formation. We therefore hypothesized that in the presence of increased l...

  2. Looking to the future: a new decade of pulmonary arterial hypertension therapy

    OpenAIRE

    V.V. McLaughlin

    2011-01-01

    Pulmonary arterial hypertension (PAH) is a severe and debilitating disease characterised by vascular proliferation and remodelling of the small pulmonary arteries, leading to a progressive increase in pulmonary vascular resistance, increased afterload on the right ventricle and, ultimately, right heart failure. Although there is no “cure” for PAH, the availability of targeted therapies over the past decade has led to major advances in the management of PAH, reflected in improvements in surviv...

  3. Therapies for pulmonary arterial hypertension: where are we today, where do we go tomorrow?

    OpenAIRE

    Andrei Seferian; Gérald Simonneau

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a progressive disease characterised by remodelling of small pulmonary arteries leading to an increased pulmonary vascular resistance, right ventricular failure and death. Available treatments try to re-establish the equilibrium on three signalling pathways: the prostacyclin, the endothelin (ET)-1 and the nitric oxide. Prostanoids, such as epoprostenol or treprostinil have a vasodilator, antiproliferative and immunomodulatory effect and, despite the adm...

  4. Are left ventricular mass, geometry and function related to vascular changes and/or insulin resistance in long-standing hypertension? ICARUS: a LIFE substudy

    DEFF Research Database (Denmark)

    Olsen, M H; Hjerkinn, E; Wachtell, K; Høieggen, A; Bella, J N; Nesbitt, S D; Fossum, E; Kjeldsen, S E; Julius, S; Ibsen, H

    2003-01-01

    with essential hypertension and electrocardiographic LV hypertrophy, we measured blood pressure; insulin sensitivity by hyperinsulinaemic euglucaemic clamp; minimal forearm vascular resistance (MFVR) by plethysmography; intima-media cross-sectional area of the common carotid arteries (IMA) by...

  5. Insulin sensitivity and carotid intima-media thickness

    DEFF Research Database (Denmark)

    Kozakova, Michaela; Natali, Andrea; Dekker, Jacqueline;

    2013-01-01

    Despite a wealth of experimental data in animal models, the independent association of insulin resistance with early carotid atherosclerosis in man has not been demonstrated. APPROACH AND RESULTS: We studied a European cohort of 525 men and 655 women (mean age, 44±8 years) free of conditions known...... repeated after 3 years. In men, baseline intima-media thickness in the common carotid artery (CCA-IMT) was significantly higher (P...

  6. Differential Effects of Diet-Induced Dyslipidemia and Hyperglycemia on Mesenteric Resistance Artery Structure and Function in Type 2 Diabetes

    OpenAIRE

    Sachidanandam, Kamakshi; Hutchinson, Jim R.; Elgebaly, Mostafa M.; Mezzetti, Erin M; Wang, Mong-Heng; Ergul, Adviye

    2008-01-01

    Type 2 diabetes and dyslipidemia oftentimes present in combination. However, the relative roles of diabetes and diet-induced dyslipidemia in mediating changes in vascular structure, mechanics, and function are poorly understood. Our hypothesis was that addition of a high-fat diet would exacerbate small artery remodeling, compliance, and vascular dysfunction in type 2 diabetes. Vascular remodeling indices [media/lumen (M/L) ratio, collagen abundance and turnover, and ma...

  7. Molecular biocoding of insulin

    Directory of Open Access Journals (Sweden)

    Lutvo Kuric

    2010-07-01

    Full Text Available Lutvo KuricNovi Travnik, Kalinska, Bosnia and Herzegovina Abstract: This paper discusses cyberinformation studies of the amino acid composition of insulin, in particular the identification of scientific terminology that could describe this phenomenon, ie, the study of genetic information, as well as the relationship between the genetic language of proteins and theoretical aspects of this system and cybernetics. The results of this research show that there is a matrix code for insulin. It also shows that the coding system within the amino acid language gives detailed information, not only on the amino acid “record”, but also on its structure, configuration, and various shapes. The issue of the existence of an insulin code and coding of the individual structural elements of this protein are discussed. Answers to the following questions are sought. Does the matrix mechanism for biosynthesis of this protein function within the law of the general theory of information systems, and what is the significance of this for understanding the genetic language of insulin? What is the essence of existence and functioning of this language? Is the genetic information characterized only by biochemical principles or it is also characterized by cyberinformation principles? The potential effects of physical and chemical, as well as cybernetic and information principles, on the biochemical basis of insulin are also investigated. This paper discusses new methods for developing genetic technologies, in particular more advanced digital technology based on programming, cybernetics, and informational laws and systems, and how this new technology could be useful in medicine, bioinformatics, genetics, biochemistry, and other natural sciences.Keywords: human insulin, insulin model, biocode, genetic code, amino acids

  8. Influence of circulating epinephrine on absorption of subcutaneously injected insulin

    International Nuclear Information System (INIS)

    Effects of epinephrine (Epi) infusion on the absorption of subcutaneously injected 125I-labeled soluble human insulin (10 U) from the thigh or the abdomen were studied in 16 healthy subjects and from the thigh in 10 insulin-dependent diabetic (IDDM) patients. Epi was infused at 0.3 (high dose) or 0.1 (low dose; healthy subjects) nmol.kg-1.min-1 i.v., resulting in arterial plasma Epi levels of approximately 6 and 2 nM, respectively. Saline was infused on a control day. Insulin absorption was measured as disappearance of radioactivity from the injection site and as appearance of plasma immunoreactive insulin (IRI). Adipose tissue blood flow was measured with the 133Xe clearance technique. First-order disappearance rate constants of 125I from the thigh depot decreased approximately 40-50% during the high dose of Epi compared with control (P less than .001). The corresponding decrease from the abdominal depot was approximately 40% (P less than .001), whereas no significant change was found during the low Epi dose. IRI fell compared with control in all groups at the high Epi dose. The Epi-induced depression of insulin absorption occurred despite unaltered or even slightly increased subcutaneous blood flow. The results indicate that circulating Epi at levels seen during moderate physical stress depresses the absorption of soluble insulin from subcutaneous injection sites to an extent that might be important for glycemic control in IDDM patients. Furthermore, dissociation is found between changes in insulin absorption and subcutaneous blood flow during Epi infusion, suggesting that factors other than blood flow may also influence the absorption of subcutaneously injected insulin

  9. Atrial Electrical Remodeling and Sleep Disordered Breathing

    Directory of Open Access Journals (Sweden)

    Adrian Baranchuk; Diego Conde

    2013-08-01

    Full Text Available To the Editor: We read with interest the article from Bitter et al. (1 published in the last volume of JAFIB. This non-systematic review covers some of the most important physiopathological aspects of the link between sleep disordered breathing (SDB and atrial fibrillation (AFib. We do agree with the authors on the role of hypertension, endothelial dysfunction and inflammation. These topics were, to our understanding and perspective, very well covered by the authors on this review. However, despite that the authors mentioned atrial remodeling a couple of times during their review, we are not sure that this topic and specifically atrial electrical remodeling, was properly discussed and referenced. The pathophysiology linking SDB to AF is multifactorial and may involve repetitive hypoxemia, increased sympathetic drive, fluctuations in intrathoracic pressure and systemic inflammation (2. These physiologic changes may induce structural and electrical remodeling serving as a substrate to the development of AFib. An indirect marker for such electrical remodeling is the prolongation of atrial conduction time, represented by increased maximum P-wave duration in the surface ECG. In a prior study, we showed that an increased P-wave duration has been associated with SDB (3. Interatrial block (IAB, defined as a surface P-wave duration > 120 ms, was more prevalent in patients with moderate-severe SDB (34.7% SDB vs. 0% controls, p 25 were independent predictors of maximum P-wave duration (p=0.001 and p<0.001 respectively (3. Another non-invasive method to determine atrial electrical remodeling is the Signal-averaged P-wave (SAPW duration. The SAPW duration represents the average of all P-wave durations in a given number of consecutive heartbeats. We recently postulated that SAPW would be useful to identify atrial electrical remodeling in patients with severe SDB and that treatment with C-PAP for 4-6 weeks may induce reverse atrial electrical remodeling (4

  10. Acute Aerobic Exercise and Plasma Levels of Orexin A, Insulin, Glucose, and Insulin Resistance in Males With Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Alizadeh

    2016-01-01

    Full Text Available Background The endocrine system disruptions are the main factors in metabolic disorders which are due to lifestyle changes, obesity, and aging. Insulin resistance is impaired glucose homeostasis in the presence of insulin and is related to many diseases such as hypertension, coronary artery disease, and type 2 diabetes Objectives This study aimed to investigate the effect of acute aerobic exercise on plasma levels of orexin A, insulin, glucose, and insulin resistance in males with type 2 diabetes. Patients and Methods Twenty subjects (mean age = 45.40 ± 5.42 years, mean weight = 80.91 ± 6.35 kg, body mass index = 25.41 ± 2.76 kg/m2 were randomly assigned into control and experimental groups, involving 10 people in each group. The exercise protocol consisted of one session of acute aerobic exercise on a treadmill at 60% maximal oxygen uptake and the same energy expenditure (300 kcal, which were determined by gas analyzers. Subjects were subjected to samplings before, immediately after, and 24 hours after the acute aerobic exercise. Results The analysis of findings in P ≤ 0.05 indicated that acute aerobic exercise caused a significant increase in plasma levels of orexin A and a significant decrease in plasma levels of glucose immediately after the aerobic activity, but insignificantly affected the plasma levels of insulin and insulin resistance. Conclusions It seems that in people with type 2 diabetes, acute aerobic exercise can decrease the plasma levels of glucose, possibly through increasing orexin A. In addition, negative energy balance is necessary to decrease the levels of insulin and insulin resistance during acute aerobic exercise.

  11. Green tea polyphenols improve cardiac muscle mRNA, and protein levels of signal pathways related to insulin and lipid metabolism and inflammation in insulin-resistant rats

    Science.gov (United States)

    Epidemiologic studies indicate that the consumption of green tea polyphenols (GTP) may reduce the risk of coronary artery disease. To explore the underlying mechanisms of action at the molecular level, we examined the effects of GTP on cardiac mRNA and protein levels of genes involved in insulin an...

  12. Relationship between serum insulin level and age and sex in 980 patients with essential hypertension

    International Nuclear Information System (INIS)

    Objective: To investigate the change of serum insulin level in essential hypertension patients and its relationship with age and sex. Methods: The levels of serum insulin were determined with radioimmunoassay in 980 essential hypertension patients and 120 controls. Results: The levels of serum insulin in the essential hypertension patients were significantly higher than those in the controls (t=4.280, P<0.01). However, there were no significant differences among the levels in different sex and age groups. The same held true for women before and after menopause as well as different stages of hypertension. Conclusion: The average serum insulin level in EH patients was significantly higher than the level in controls, and had positive correlation to mean arterial pressure. But no significant differences were found among different sex and age groups, so serum insulin could be a new independent risk factor of essential hypertension

  13. Distal vessel stiffening is an early and pivotal mechanobiological regulator of vascular remodeling and pulmonary hypertension

    Science.gov (United States)

    Liu, Fei; Haeger, Christina Mallarino; Dieffenbach, Paul B.; Sicard, Delphine; Chrobak, Izabela; Coronata, Anna Maria F.; Suárez Velandia, Margarita M.; Vitali, Sally; Colas, Romain A.; Norris, Paul C.; Marinković, Aleksandar; Liu, Xiaoli; Ma, Jun; Rose, Chase D.; Lee, Seon-Jin; Comhair, Suzy A.A.; Erzurum, Serpil C.; McDonald, Jacob D.; Serhan, Charles N.; Walsh, Stephen R.; Tschumperlin, Daniel J.; Fredenburgh, Laura E.

    2016-01-01

    Pulmonary arterial (PA) stiffness is associated with increased mortality in patients with pulmonary hypertension (PH); however, the role of PA stiffening in the pathogenesis of PH remains elusive. Here, we show that distal vascular matrix stiffening is an early mechanobiological regulator of experimental PH. We identify cyclooxygenase-2 (COX-2) suppression and corresponding reduction in prostaglandin production as pivotal regulators of stiffness-dependent vascular cell activation. Atomic force microscopy microindentation demonstrated early PA stiffening in experimental PH and human lung tissue. Pulmonary artery smooth muscle cells (PASMC) grown on substrates with the stiffness of remodeled PAs showed increased proliferation, decreased apoptosis, exaggerated contraction, enhanced matrix deposition, and reduced COX-2–derived prostanoid production compared with cells grown on substrates approximating normal PA stiffness. Treatment with a prostaglandin I2 analog abrogated monocrotaline-induced PA stiffening and attenuated stiffness-dependent increases in proliferation, matrix deposition, and contraction in PASMC. Our results suggest a pivotal role for early PA stiffening in PH and demonstrate the therapeutic potential of interrupting mechanobiological feedback amplification of vascular remodeling in experimental PH. PMID:27347562

  14. Phosphodiesterase type 5 inhibitors in the treatment of pulmonary arterial hypertension

    OpenAIRE

    Kadriye Kılıçkesmez; M. Serdar Küçükoğlu

    2010-01-01

    The pathology of pulmonary arterial hypertension (PAH) is characterized by vascular vasoconstriction, smooth muscle cell proliferation, and thrombosis. Experimental studies have shown the beneficial effect of phosphodiesterase type 5 (PDE-5) inhibitors on pulmonary vascular remodeling and vasodilatation. Randomized clinical trials in monotherapy or combination therapy have been conducted in PAH with sildenafil and tadalafil which significantly improve clinical status, exercise capacity and he...

  15. Ovarian tumors secreting insulin.

    Science.gov (United States)

    Battocchio, Marialberta; Zatelli, Maria Chiara; Chiarelli, Silvia; Trento, Mariangela; Ambrosio, Maria Rosaria; Pasquali, Claudio; De Carlo, Eugenio; Dassie, Francesca; Mioni, Roberto; Rebellato, Andrea; Fallo, Francesco; Degli Uberti, Ettore; Martini, Chiara; Vettor, Roberto; Maffei, Pietro

    2015-08-01

    Combined ovarian germ cell and neuroendocrine tumors are rare. Only few cases of hyperinsulinism due to ovarian ectopic secretion have been hypothesized in the literature. An ovarian tumor was diagnosed in a 76-year-old woman, referred to our department for recurrent hypoglycemia with hyperinsulinism. In vivo tests, in particular fasting test, rapid calcium infusion test, and Octreotide test were performed. Ectopic hyperinsulinemic hypoglycemia was demonstrated in vivo and hypoglycemia disappeared after hysteroadnexectomy. Histological exam revealed an ovarian germ cell tumor with neuroendocrine and Yolk sac differentiation, while immunostaining showed insulin positivity in neuroendocrine cells. A cell culture was obtained by tumoral cells, testing Everolimus, and Pasireotide. Insulin was detected in cell culture medium and Everolimus and Pasireotide demonstrated their potentiality in reducing insulin secretion, more than controlling cell viability. Nine cases of hyperinsulinism due to ovarian ectopic secretion reported in literature have been reviewed. These data confirm the ovarian tissue potentiality to induce hyperinsulinemic hypoglycemic syndrome after neoplastic transformation. PMID:25896552

  16. Insulin and carbohydrate dysregulation.

    Science.gov (United States)

    Gelato, Marie C

    2003-04-01

    Patients with human immunodeficiency virus receiving highly active antiretroviral therapy (HAART) may experience abnormal body composition changes as well as metabolic abnormalities, including dyslipidemia, increases in triglycerides, low high-density lipoprotein cholesterol levels, and abnormal carbohydrate metabolism, ranging from insulin resistance with and without glucose intolerance to frank diabetes. Whether the body composition changes (i.e., increased visceral adiposity and fat wasting in the peripheral tissues) are linked to abnormalities in carbohydrate metabolism is unclear. The use of HAART with and without therapy with protease inhibitors (PIs) is related to carbohydrate abnormalities and changes in body composition. Regimens that include PIs appear to have a higher incidence of insulin resistance (up to 90%) and diabetes mellitus (up to 40%). The etiology of these abnormalities is not well understood; what is known about insulin and carbohydrate dysregulation with HAART is discussed. PMID:12652377

  17. Insulin C-peptide test

    Science.gov (United States)

    C-peptide ... the test depends on the reason for the C-peptide measurement. Ask your health care provider if ... C-peptide is measured to tell the difference between insulin produced by the body and insulin injected ...

  18. Eosinophil-Mediated Cholinergic Nerve Remodeling

    OpenAIRE

    Durcan, Niamh; Costello, Richard W; McLean, W. Graham; Blusztajn, Jan; Madziar, Beata; Fenech, Anthony G; Hall, Ian P; Gleich, Gerard J.; McGarvey, Lorcan; Walsh, Marie-Therese

    2006-01-01

    Eosinophils are observed to localize to cholinergic nerves in a variety of inflammatory conditions such as asthma, rhinitis, eosinophilic gastroenteritis, and inflammatory bowel disease, where they are also responsible for the induction of cell signaling.Wehypothesized that a consequence of eosinophil localization to cholinergic nerves would involve a neural remodeling process. Eosinophil co-culture with cholinergic IMR32 cells led to increased expression of the M2 muscar...

  19. PHAGOCYTOSIS AND REMODELING OF COLLAGEN MATRICES

    OpenAIRE

    Abraham, Leah C.; Dice, J. Fred; Lee, Kyongbum; Kaplan, David L.

    2007-01-01

    The biodegradation of collagen and the deposition of new collagen-based extracellular matrices are of central importance in tissue remodeling and function. Similarly, for collagen-based biomaterials used in tissue engineering, the degradation of collagen scaffolds with accompanying cellular infiltration and generation of new extracellular matrix is critical for integration of in vitro grown tissues in vivo. In earlier studies we observed significant impact of collagen structure on primary lun...

  20. Cell wall remodeling under abiotic stress

    OpenAIRE

    Tenhaken, Raimund

    2015-01-01

    Plants exposed to abiotic stress respond to unfavorable conditions on multiple levels. One challenge under drought stress is to reduce shoot growth while maintaining root growth, a process requiring differential cell wall synthesis and remodeling. Key players in this process are the formation of reactive oxygen species (ROS) and peroxidases, which initially cross-link phenolic compounds and glycoproteins of the cell walls causing stiffening. The function of ROS shifts after having converted a...

  1. Adipokines and Hepatic Insulin Resistance

    OpenAIRE

    Yu Li; Lin Ding; Waseem Hassan; Daoud Abdelkader; Jing Shang

    2013-01-01

    Obesity is a major risk factor for insulin resistance and type 2 diabetes. Adipose tissue is now considered to be an active endocrine organ that secretes various adipokines such as adiponectin, leptin, resistin, tumour necrosis factor-α, and interleukin-6. Recent studies have shown that these factors might provide a molecular link between increased adiposity and impaired insulin sensitivity. Since hepatic insulin resistance plays the key role in the whole body insulin resistance, clarificatio...

  2. Application of Petri Nets in Bone Remodeling

    Directory of Open Access Journals (Sweden)

    Lingxi Li

    2009-07-01

    Full Text Available Understanding a mechanism of bone remodeling is a challenging task for both life scientists and model builders, since this highly interactive and nonlinear process can seldom be grasped by simple intuition. A set of ordinary differential equations (ODEs have been built for simulating bone formation as well as bone resorption. Although solving ODEs numerically can provide useful predictions for dynamical behaviors in a continuous time frame, an actual bone remodeling process in living tissues is driven by discrete events of molecular and cellular interactions. Thus, an event-driven tool such as Petri nets (PNs, which may dynamically and graphically mimic individual molecular collisions or cellular interactions, seems to augment the existing ODE-based systems analysis. Here, we applied PNs to expand the ODE-based approach and examined discrete, dynamical behaviors of key regulatory molecules and bone cells. PNs have been used in many engineering areas, but their application to biological systems needs to be explored. Our PN model was based on 8 ODEs that described an osteoprotegerin linked molecular pathway consisting of 4 types of bone cells. The models allowed us to conduct both qualitative and quantitative evaluations and evaluate homeostatic equilibrium states. The results support that application of PN models assists understanding of an event-driven bone remodeling mechanism using PN-specific procedures such as places, transitions, and firings.

  3. Metabolic reprogramming and inflammation act in concert to control vascular remodeling in hypoxic pulmonary hypertension.

    Science.gov (United States)

    Stenmark, Kurt R; Tuder, Rubin M; El Kasmi, Karim C

    2015-11-15

    Pulmonary hypertension (PH) is a complex, multifactorial syndrome that remains poorly understood despite decades of research. PH is characterized by profound pulmonary artery (PA) remodeling that includes significant fibro-proliferative and inflammatory changes of the PA adventitia. In line with the emerging concept that PH shares key features with cancer, recent work centers on the idea that PH results from a multistep process driven by reprogramming of gene-expression patterns that govern changes in cell metabolism, inflammation, and proliferation. Data demonstrate that in addition to PA endothelial cells and smooth muscle cells, adventitial fibroblasts from animals with experimental hypoxic PH and from humans with PH (hereafter, termed PH-Fibs) exhibit proinflammatory activation, increased proliferation, and apoptosis resistance, all in the context of metabolic reprogramming to aerobic glycolysis. PH-Fibs can also recruit, retain, and activate naïve macrophages (Mϕ) toward a proinflammatory/proremodeling phenotype through secretion of chemokines, cytokines, and glycolytic metabolites, among which IL-6 and lactate play key roles. Furthermore, these fibroblast-activated Mϕ (hereafter, termed FAMϕ) exhibit aerobic glycolysis together with high expression of arginase 1, Vegfa, and I1lb, all of which require hypoxia-inducible factor 1α and STAT3 signaling. Strikingly, in situ, the adventitial Mϕ phenotype in the remodeled PA closely resembles the Mϕ phenotype induced by fibroblasts in vitro (FAMϕ), suggesting that FAMϕ crosstalk involving metabolic and inflammatory signals is a critical, pathogenetic component of vascular remodeling. This review discusses metabolic and inflammatory changes in fibroblasts and Mϕ in PH with the goal of raising ideas about new interventions to abrogate remodeling in hypoxic forms of PH. PMID:25930027

  4. Extracellular matrix remodelling in response to venous hypertension: proteomics of human varicose veins

    Science.gov (United States)

    Barallobre-Barreiro, Javier; Oklu, Rahmi; Lynch, Marc; Fava, Marika; Baig, Ferheen; Yin, Xiaoke; Barwari, Temo; Potier, David N.; Albadawi, Hassan; Jahangiri, Marjan; Porter, Karen E.; Watkins, Michael T.; Misra, Sanjay; Stoughton, Julianne; Mayr, Manuel

    2016-01-01

    Aims Extracellular matrix remodelling has been implicated in a number of vascular conditions, including venous hypertension and varicose veins. However, to date, no systematic analysis of matrix remodelling in human veins has been performed. Methods and results To understand the consequences of venous hypertension, normal and varicose veins were evaluated using proteomics approaches targeting the extracellular matrix. Varicose saphenous veins removed during phlebectomy and normal saphenous veins obtained during coronary artery bypass surgery were collected for proteomics analysis. Extracellular matrix proteins were enriched from venous tissues. The proteomics analysis revealed the presence of >150 extracellular matrix proteins, of which 48 had not been previously detected in venous tissue. Extracellular matrix remodelling in varicose veins was characterized by a loss of aggrecan and several small leucine-rich proteoglycans and a compensatory increase in collagen I and laminins. Gene expression analysis of the same tissues suggested that the remodelling process associated with venous hypertension predominantly occurs at the protein rather than the transcript level. The loss of aggrecan in varicose veins was paralleled by a reduced expression of aggrecanases. Chymase and tryptase β1 were among the up-regulated proteases. The effect of these serine proteases on the venous extracellular matrix was further explored by incubating normal saphenous veins with recombinant enzymes. Proteomics analysis revealed extensive extracellular matrix degradation after digestion with tryptase β1. In comparison, chymase was less potent and degraded predominantly basement membrane-associated proteins. Conclusion The present proteomics study provides unprecedented insights into the expression and degradation of structural and regulatory components of the vascular extracellular matrix in varicosis. PMID:27068509

  5. Left ventricular remodeling and hypertrophy in patients with aortic stenosis: insights from cardiovascular magnetic resonance

    Directory of Open Access Journals (Sweden)

    Dweck Marc R

    2012-07-01

    Full Text Available Abstract Background Cardiovascular magnetic resonance (CMR is the gold standard non-invasive method for determining left ventricular (LV mass and volume but has not been used previously to characterise the LV remodeling response in aortic stenosis. We sought to investigate the degree and patterns of hypertrophy in aortic stenosis using CMR. Methods Patients with moderate or severe aortic stenosis, normal coronary arteries and no other significant valve lesions or cardiomyopathy were scanned by CMR with valve severity assessed by planimetry and velocity mapping. The extent and patterns of hypertrophy were investigated using measurements of the LV mass index, indexed LV volumes and the LV mass/volume ratio. Asymmetric forms of remodeling and hypertrophy were defined by a regional wall thickening ≥13 mm and >1.5-fold the thickness of the opposing myocardial segment. Results Ninety-one patients (61±21 years; 57 male with aortic stenosis (aortic valve area 0.93±0.32cm2 were recruited. The severity of aortic stenosis was unrelated to the degree (r2=0.012, P=0.43 and pattern (P=0.22 of hypertrophy. By univariate analysis, only male sex demonstrated an association with LV mass index (P=0.02. Six patterns of LV adaption were observed: normal ventricular geometry (n=11, concentric remodeling (n=11, asymmetric remodeling (n=11, concentric hypertrophy (n=34, asymmetric hypertrophy (n=14 and LV decompensation (n=10. Asymmetric patterns displayed considerable overlap in appearances (wall thickness 17±2mm with hypertrophic cardiomyopathy. Conclusions We have demonstrated that in patients with moderate and severe aortic stenosis, the pattern of LV adaption and degree of hypertrophy do not closely correlate with the severity of valve narrowing and that asymmetric patterns of wall thickening are common. Trial registration ClinicalTrials.gov Reference Number: NCT00930735

  6. Insulin-induced localized lipoatrophy:

    OpenAIRE

    Breznik, Vesna; Kokol, Rok; Luzar, Boštjan; Miljković, Jovan

    2013-01-01

    Insulin lipoatrophy is a rare immunologic cutaneous complication in diabetes mellitus that presents with localized subcutaneous fat atrophy at the insulin injection site. We report the case of a 62-year-old woman with type 2 diabetes mellitus that developed localized lipoatrophy on the abdomen after 6 years of therapy with the insulin analogues detemir and aspart.

  7. Cinnamon, glucose and insulin sensitivity

    Science.gov (United States)

    Compounds found in cinnamon not only improve the function of insulin but also function as antioxidants and may be anti-inflammatory. This is very important since insulin function, antioxidant status, and inflammatory response are closely linked; with decreased insulin sensitivity there is also decr...

  8. Central airways remodeling in COPD patients

    Directory of Open Access Journals (Sweden)

    Pini L

    2014-09-01

    Full Text Available Laura Pini,1 Valentina Pinelli,2 Denise Modina,1 Michela Bezzi,3 Laura Tiberio,4 Claudio Tantucci1 1Unit of Respiratory Medicine, Department of Clinical and Experimental Sciences, University of Brescia, 2Department of Respiratory Medicine, Spedali Civili di Brescia, 3Department Bronchoscopy, Spedali Civili di Brescia, 4Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy Background: The contribution to airflow obstruction by the remodeling of the peripheral airways in chronic obstructive pulmonary disease (COPD patients has been well documented, but less is known about the role played by the large airways. Few studies have investigated the presence of histopathological changes due to remodeling in the large airways of COPD patients. Objectives: The aim of this study was to verify the presence of airway remodeling in the central airways of COPD patients, quantifying the airway smooth muscle (ASM area and the extracellular matrix (ECM protein deposition, both in the subepithelial region and in the ASM, and to verify the possible contribution to airflow obstruction by the above mentioned histopathological changes. Methods: Biopsies of segmental bronchi spurs were performed in COPD patients and control smoker subjects and immunostained for collagen type I, versican, decorin, biglycan, and alpha-smooth muscle actin. ECM protein deposition was measured at both subepithelial, and ASM layers. Results: The staining for collagen I and versican was greater in the subepithelial layer of COPD patients than in control subjects. An inverse correlation was found between collagen I in the subepithelial layer and both forced expiratory volume in 1 second and ratio between forced expiratory volume in 1 second and forced vital capacity. A statistically significant increase of the ASM area was observed in the central airways of COPD patients versus controls. Conclusion: These findings indicate that airway remodeling also affects

  9. Insulin Degludec, The New Generation Basal Insulin or Just another Basal Insulin?

    OpenAIRE

    Sami N. Nasrallah; L. Raymond Reynolds

    2012-01-01

    The advances in recombinant DNA technology have led to an improvement in the properties of currently available long-acting insulin analogs. Insulin degludec, a new generation ultra-long-acting basal insulin, currently in phase 3 clinical trials, has a promising future in clinical use. When compared to its rival basal insulin analogs, a longer duration of action and lower incidence of hypoglycemic events in both type 1 and type 2 diabetic patients has been demonstrated.1,2 Its unique mechanism...

  10. Interleukin-2/Anti-Interleukin-2 Immune Complex Attenuates Cardiac Remodeling after Myocardial Infarction through Expansion of Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Zhipeng Zeng

    2016-01-01

    Full Text Available CD4+CD25+Foxp3+ regulatory T cells (Treg cells have protective effects in wound healing and adverse ventricular remodeling after myocardial infarction (MI. We hypothesize that the interleukin- (IL- 2 complex comprising the recombinant mouse IL-2/anti-IL-2 mAb (JES6-1 attenuates cardiac remodeling after MI through the expansion of Treg. Mice were subjected to surgical left anterior descending coronary artery ligation and treated with either PBS or IL-2 complex. The IL-2 complex significantly attenuates ventricular remodeling, as demonstrated by reduced infarct size, improved left ventricular (LV function, and attenuated cardiomyocyte apoptosis. The IL-2 complex increased the percentage of CD4+CD25+Foxp3+ Treg cells, which may be recruited to the infarcted heart, and decreased the frequencies of IFN-γ- and IL-17-producing CD4+ T helper (Th cells among the CD4+Foxp3− T cells in the spleen. Furthermore, the IL-2 complex inhibited the gene expression of proinflammatory cytokines as well as macrophage infiltrates in the infarcted myocardium and induced the differentiation of macrophages from M1 to M2 phenotype in border zone of infarcted myocardium. Our studies indicate that the IL-2 complex may serve as a promising therapeutic approach to attenuate adverse remodeling after MI through expanding Treg cells specifically.

  11. Insulin som trickster

    DEFF Research Database (Denmark)

    Lassen, Aske Juul

    2011-01-01

    grænser nedbrydes i en konstant penetrering af huden, når blodsukkeret måles eller insulinen indsprøjtes. Insulin analyseres som en tricksterfigur, der udøver et grænsearbejde på kroppen, leger med dens kategorier og vender forholdet mellem gift og medicin, frihed og ufrihed, kunstighed og naturlighed...

  12. Polyethyleneglycol RIA (radioimmunoassay) insulin

    International Nuclear Information System (INIS)

    Insulin is a polypeptide hormone of M.W. 6,000 composed of two peptide chains, A and B, jointed by two cross-linked disulphide bonds and synthesized by the beta-cells of the islets of Langerhans of the pancreas. Insulin influences most of the metabolic functions of the body. Its best known action is to lower the blood glucose concentration by increasing the rate at which glucose is converted to glycogen in the liver and muscles and to fat in adipose tissue, by stimulating the rate of glucose metabolism and by depressing gluconeogenesis. Insulin stimulates the synthesis of proteins, DNA and RNA in cells generally, and promotes the uptake of aminoacids and their incorporation into muscle protein. It increases the uptake of glucose in adipose tissue and its conversion into fat and inhibits lipolysis. Insulin primary action is on the cell membrane, where it probably facilitates the transport of glucose and aminoacids into the cells. At the same time it may activate intracellular enzymes such as glycogen synthetase, concerned with glycogen synthesis. (Author)

  13. Estradiol Binds to Insulin and Insulin Receptor Decreasing Insulin Binding in vitro

    Directory of Open Access Journals (Sweden)

    RobertRoot-Bernstein

    2014-07-01

    Methods: Ultraviolet spectroscopy, capillary electrophoresis and NMR demonstrated estrogen binding to insulin and its receptor. Horse-radish peroxidase-linked insulin was used in an ELISA-like procedure to measure the effect of estradiol on binding of insulin to its receptor. Measurements: Binding constants for estrogens to insulin and the insulin receptor were determined by concentration-dependent spectral shifts. The effect of estradiol on insulin-HRP binding to its receptor was determined by shifts in the insulin binding curve. Main Results: Estradiol bound to insulin with a Kd of 12 x 10-9 M and to the insulin receptor with a Kd of 24 x 10-9 M, while other hormones had significantly less affinity. 200 nM estradiol shifted the binding curve of insulin to its receptor 0.8 log units to the right. Conclusions: Estradiol concentrations in many hyperestrogenemic syndromes are sufficient to interfere with insulin binding to its receptor producing significant insulin resistance.

  14. Insulin gene mutations and diabetes

    OpenAIRE

    Nishi, Masahiro; Nanjo, Kishio

    2011-01-01

    Abstract Some mutations of the insulin gene cause hyperinsulinemia or hyperproinsulinemia. Replacement of biologically important amino acid leads to defective receptor binding, longer half‐life and hyperinsulinemia. Three mutant insulins have been identified: (i) insulin Chicago (F49L or PheB25Leu); (ii) insulin Los Angeles (F48S or PheB24Ser); (iii) and insulin Wakayama (V92L or ValA3Leu). Replacement of amino acid is necessary for proinsulin processing results in hyperproinsulinemia. Four t...

  15. Insulin Modifies Honeybee Worker Behavior

    Directory of Open Access Journals (Sweden)

    Christine M. Mott

    2012-10-01

    Full Text Available The insulin signaling pathway has been hypothesized to play a key role in regulation of worker social insect behavior. We tested whether insulin treatment has direct effects on worker honeybee behavior in two contexts, sucrose response thresholds in winter bees and the progression to foraging by summer nurse bees. Treatment of winter worker bees with bovine insulin, used as a proxy for honeybee insulin, increased the bees’ sucrose response threshold. Treatment of summer nurse bees with bovine insulin significantly decreased the age at which foraging was initiated. This work provides further insight into the role of endocrine controls in behavior of in honeybees and insects in general.

  16. On arterial physiology, pathophysiology of vascular compliance, and cardiovascular disease.

    Science.gov (United States)

    Glasser, S P

    2000-01-01

    Traditionally, the main emphasis in hypertension treatment has been on lowering diastolic blood pressure. Recently, this emphasis has been shifting toward systolic blood pressure and pulse pressure, the latter of which might be a better indicator of future clinical events than either blood pressure reading alone or in combination. Increased pulse pressure indicates increased arterial stiffness and hence is commonly seen in older subjects. As patients age and vessels stiffen, there is a resulting loss of arterial compliance, the ability of the vessel to store blood volume temporarily as it is ejected with each systole. The arterial system acts like a Windkessel, or pump, as it converts intermittent flow from the heart into continuous flow to the organs. The process of stiffening occurs via vascular remodeling, a redistribution of the heterogeneous elements of the vascular wall. Endothelial dysfunction can trigger this remodeling process, increasing stiffness, raising blood pressure and pulse pressure, and ultimately leading to atherosclerosis, plaque formation, and attendant clinical events. Because angiotensin-converting enzyme inhibitors and calcium antagonists can restore arterial compliance, they are suitable choices for hypertension treatment when it is complicated by vascular stiffness. PMID:11728285

  17. Clarifying the anatomy of the fifth arch artery

    Directory of Open Access Journals (Sweden)

    Saurabh Kumar Gupta

    2016-01-01

    Full Text Available The artery allegedly forming in the fifth pharyngeal arch has increasingly been implicated as responsible for various vascular malformations in patients with congenitally malformed hearts. Observations from studies on developing embryos, however, have failed to provide support to substantiate several of these inferences such that the very existence of the fifth arch artery remains debatable. To the best of our knowledge, in only a solitary human embryo has a vascular channel been found that truly resembled the artery of the fifth arch. Despite the meager evidence to support its existence, the fifth arch artery has been invoked to explain the morphogenesis of double-barreled aorta, some unusual forms of aortopulmonary communications, and abnormalities of the brachiocephalic arteries. In most of these instances, the interpretations have proved fallible when examined in the light of existing knowledge of cardiac development. In our opinion, there are more plausible alternative explanations for the majority of these descriptions. Double-barreled aorta is more likely to result from retention of the recently identified dorsal collateral channels while abnormalities of brachiocephalic arteries are better explained on the basis of extensive remodeling of aortic arches during fetal development. Some examples of aortopulmonary communications, nonetheless, may well represent persistence of the developing artery of the fifth pharyngeal arch. We here present one such case - a patient with tetralogy of Fallot and pulmonary atresia, in whom the fifth arch artery provided a necessary communication between the ascending aorta and the pulmonary arteries. In this light, we discuss the features we consider to be essential before attaching the tag of "fifth arch artery" to a candidate vascular channel.

  18. Adipocyte lipolysis and insulin resistance.

    Science.gov (United States)

    Morigny, Pauline; Houssier, Marianne; Mouisel, Etienne; Langin, Dominique

    2016-06-01

    Obesity-induced insulin resistance is a major risk factor for the development of type 2 diabetes. Basal fat cell lipolysis (i.e., fat cell triacylglycerol breakdown into fatty acids and glycerol in the absence of stimulatory factors) is elevated during obesity and is closely associated with insulin resistance. Inhibition of adipocyte lipolysis may therefore be a promising therapeutic strategy for treating insulin resistance and preventing obesity-associated type 2 diabetes. In this review, we explore the relationship between adipose lipolysis and insulin sensitivity. After providing an overview of the components of fat cell lipolytic machinery, we describe the hypotheses that may support the causality between lipolysis and insulin resistance. Excessive circulating fatty acids may ectopically accumulate in insulin-sensitive tissues and impair insulin action. Increased basal lipolysis may also modify the secretory profile of adipose tissue, influencing whole body insulin sensitivity. Finally, excessive fatty acid release may also worsen adipose tissue inflammation, a well-known parameter contributing to insulin resistance. Partial genetic or pharmacologic inhibition of fat cell lipases in mice as well as short term clinical trials using antilipolytic drugs in humans support the benefit of fat cell lipolysis inhibition on systemic insulin sensitivity and glucose metabolism, which occurs without an increase of fat mass. Modulation of fatty acid fluxes and, putatively, of fat cell secretory pattern may explain the amelioration of insulin sensitivity whereas changes in adipose tissue immune response do not seem involved. PMID:26542285

  19. Managing diabetes with inhaled insulin

    Directory of Open Access Journals (Sweden)

    Lucy D Mastrandrea

    2012-01-01

    Full Text Available The incidence of diabetes is increasing world-wide. Many individuals with diabetes require insulin to control their blood sugar and prevent both microvascular and macrovascular complications associated with this chronic disease. Current regimens involve delivery of subcutaneous insulin by injection or continuous insulin infusion. One area of research to advance diabetes care is aimed at developing alternate routes of insulin administration that will make daily management less invasive for patients. This review will focus on inhaled insulin, a novel formulation which takes advantage of drug delivery through the pulmonary system. The pharmacology, efficacy, and safety of inhaled insulin will be discussed. In addition, the status of inhaled insulin as a potential therapy for individuals with diabetes will be reviewed.

  20. Insulin degludec for diabetes mellitus.

    Science.gov (United States)

    2013-07-01

    Over the last few years there has been a steady increase in the number of prescriptions dispensed in primary care for intermediate and long-acting insulin analogues and a reduction in prescriptions for biphasic isophane insulin. For example, in England, the volume of intermediate and long-acting insulin analogues in general practice has risen from approximately 650,000 prescriptions per quarter in 2007 to over 850,000 per quarter in 2012.(1) ▾Insulin degludec (Tresiba, Novo Nordisk) is a new long acting basal insulin analogue for the management of diabetes mellitus in adults.(2) Two strengths of insulin degludec (100 units/mL and 200 units/mL) were launched in the UK in February 2013. Here we discuss evidence for the effectiveness and safety of insulin degludec. PMID:23842634

  1. Simultaneous stent expansion/balloon deflation technique to salvage failed balloon remodeling.

    Science.gov (United States)

    Ladner, Travis R; He, Lucy; Davis, Brandon J; Froehler, Michael T; Mocco, J

    2016-04-01

    Herniation, with possible embolization, of coils into the parent vessel following aneurysm coiling remains a frequent challenge. For this reason, balloon or stent assisted embolization remains an important technique. Despite the use of balloon remodeling, there are occasions where, on deflation of the balloon, some coils, or even the entire coil mass, may migrate. We report the successful use of a simultaneous adjacent stent deployment bailout technique in order to salvage coil prolapse during balloon remodeling in three patients. Case No 1 was a wide neck left internal carotid artery bifurcation aneurysm, measuring 9 mm×7.9 mm×6 mm with a 5 mm neck. Case No 2 was a complex left superior hypophyseal artery aneurysm, measuring 5.3 mm×4 mm×5 mm with a 2.9 mm neck. Case No 3 was a ruptured right posterior communicating artery aneurysm, measuring 4 mm×4 mm×4.5 mm with a 4 mm neck. This technique successfully returned the prolapsed coil mass into the aneurysm sac in all cases without procedural complications. The closed cell design of the Enterprise VRD (Codman and Shurtleff Inc, Raynham, Massachusetts, USA) makes it ideal for this bailout technique, by allowing the use of an 0.021 inch delivery catheter (necessary for simultaneous access) and by avoiding the possibility of an open cell strut getting caught on the deflated balloon. We hope this technique will prove useful to readers who may find themselves in a similar predicament. PMID:25801773

  2. Insulin resistance and hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Manuel Romero-Gómez

    2006-01-01

    Insulin resistance is the major feature of the metabolic syndrome and depends on insulin secretion and insulin sensitivity. In chronic hepatitis C, insulin resistance and type 2 diabetes mellitus are more often seen than in healthy controls or chronic hepatitis B patients.Hepatitis C virus (HCV) infection promotes insulin resistance, mainly by increased TNF production together with enhancement of suppressor of cytokine (SOC-3); both events block PI3K and Akt phosphorylation. Two types of insulin resistance could be found in chronic hepatitis C patients: "viral" and "metabolic" insulin resistance. Insulin resistance in chronic hepatitis C is relevant because it promotes steatosis and fibrosis. The mechanisms by which insulin resistance promotes fibrosis progression include: (1) steatosis, (2) hyperleptinemia, (3) increased TNF production, (4) impaired expression of PPARy receptors. Lastly, insulin resistance has been found as a common denominator in patients difficult-to-treat like cirrhotics, overweight, HIV coinfected and Afro-American.Insulin resistance together with fibrosis and genotype has been found to be independently associated with impaired response rate to peginterferon plus ribavirin.Indeed, in genotype 1, the sustained response rate was twice (60%) in patients with HOMA ≤ 2 than patients with HOMA > 2. In experiments carried out on Huh-7cells transfected by full length HCVRNA, interferon alpha blocks HCV replication. However, when insulin (at doses of 128 μU/mL, similar that seen in the hyperinsulinemic state) was added to interferon, the ability to block HCV replication disappeared, and the PKR synthesis was abolished. In summary, hepatitis C promotes insulin resistance and insulin resistance induces interferon resistance,steatosis and fibrosis progression.

  3. Superactive insulin: [B10-aspartic acid]insulin(human)

    International Nuclear Information System (INIS)

    The genetic basis for a case of familial hyperproinsulinemia has been elucidated recently. It involves a single point mutation in the proinsulin gene resulting in the substitution of aspartic acid for histidine-10 of the B chain of insulin. The authors have synthesized a human insulin analogue, [Asp/sup B10/] insulin, corresponding to the mutant proinsulin and evaluated its biological activity. [Asp/sup B10/] Insulin displayed a binding affinity to insulin receptors in rat liver plasma membranes that was 534 +- 146% relative to the natural hormone. In lipogenesis assays, the synthetic analogue exhibited a potency that was 435 +- 144% relative to insulin, which is statistically not different from its binding affinity. Reversed-phase HPLC indicated that the synthetic analogue is more apolar than natural insulin. They suggest that the observed properties reflect changes in the conformation of the analogue relative to natural insulin, which results in a stronger interaction with the insulin receptor. Thus, a single substitution of an amino acid residue of human insulin has resulted in a superactive hormone

  4. Superactive insulin: (B10-aspartic acid)insulin(human)

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, G.P.; Burke, G.T.; Katsoyannis, P.G.

    1987-09-01

    The genetic basis for a case of familial hyperproinsulinemia has been elucidated recently. It involves a single point mutation in the proinsulin gene resulting in the substitution of aspartic acid for histidine-10 of the B chain of insulin. The authors have synthesized a human insulin analogue, (Asp/sup B10/) insulin, corresponding to the mutant proinsulin and evaluated its biological activity. (Asp/sup B10/) Insulin displayed a binding affinity to insulin receptors in rat liver plasma membranes that was 534 +- 146% relative to the natural hormone. In lipogenesis assays, the synthetic analogue exhibited a potency that was 435 +- 144% relative to insulin, which is statistically not different from its binding affinity. Reversed-phase HPLC indicated that the synthetic analogue is more apolar than natural insulin. They suggest that the observed properties reflect changes in the conformation of the analogue relative to natural insulin, which results in a stronger interaction with the insulin receptor. Thus, a single substitution of an amino acid residue of human insulin has resulted in a superactive hormone.

  5. Treatment satisfaction and quality of life with insulin glargine plus insulin lispro compared with NPH insulin plus unmodified human insulin in people with Type 1 diabetes

    OpenAIRE

    Ashwell , SG; Stephens, JW; Witthaus, E; Home, PD; Bradley, Clare

    2008-01-01

    OBJECTIVE— The purpose of this study was to compare quality of life and treatment satisfaction using insulin glargine plus insulin lispro with that using NPH insulin plus unmodified human insulin in adults with type 1 diabetes managed with multiple injection regimens. RESEARCH DESIGN AND METHODS— As part of a 32-week, five-center, two-way crossover study in 56 individuals with type 1 diabetes randomized to evening insulin glargine plus mealtime insulin lispro or to NPH insulin (once or twi...

  6. Relaxin mediates uterine artery compliance during pregnancy and increases uterine blood flow.

    Science.gov (United States)

    Vodstrcil, Lenka A; Tare, Marianne; Novak, Jacqueline; Dragomir, Nicoleta; Ramirez, Rolando J; Wlodek, Mary E; Conrad, Kirk P; Parry, Laura J

    2012-10-01

    Normal pregnancy involves dramatic remodeling of the uterine vasculature, with abnormal vascular adaptations contributing to pregnancy diseases such as preeclampsia. The peptide hormone relaxin is important for the renal and systemic hemodynamic adaptations to pregnancy, and has been shown to increase arterial compliance and outward hypertrophic remodeling. Therefore, we investigated the possibility that relaxin acts on its receptor, RXFP1, to mediate uterine artery compliance in late pregnancy and increase uterine blood flow velocity in rats. RXFP1 was predominantly localized to the tunica media vascular smooth muscle cells in the uterine artery, although receptors were also detected in endothelial cells. Highest expression of Rxfp1 in the uterine artery occurred in estrus and early pregnancy. Isolated uterine arteries from late pregnant rats treated with a monoclonal antibody against circulating relaxin (MCA1) had significantly increased vessel wall stiffness compared with controls, with no reduction in wall thickness. Chronic infusion of relaxin (4 μg/h, osmotic minipump) for 5 d in nonpregnant rats significantly increased uterine artery blood flow velocity. Overall, these data demonstrate a functional role for relaxin in mediating uterine artery compliance in pregnant rats, which may be necessary to maintain adequate uterine blood flow to the uterus and placenta. PMID:22744867

  7. Effect of training on insulin sensitivity of glucose uptake and lipolysis in human adipose tissue

    DEFF Research Database (Denmark)

    Stallknecht, B; Larsen, J J; Mikines, K J; Simonsen, L; Bülow, J; Galbo, H

    2000-01-01

    Training increases insulin sensitivity of both whole body and muscle in humans. To investigate whether training also increases insulin sensitivity of adipose tissue, we performed a three-step hyperinsulinemic, euglycemic clamp in eight endurance-trained (T) and eight sedentary (S) young men...... [insulin infusion rates: 10,000 (step I), 20,000 (step II), and 150,000 (step III) microU x min(-1) x m(-2)]. Glucose and glycerol concentrations were measured in arterial blood and also by microdialysis in interstitial fluid in periumbilical, subcutaneous adipose tissue and in quadriceps femoris muscle...... (glucose only). Adipose tissue blood flow was measured by (133)Xe washout. In the basal state, adipose tissue blood flow tended to be higher in T compared with S subjects, and in both groups blood flow was constant during the clamp. The change from basal in arterial-interstitial glucose concentration...

  8. MicroRNA Expression Signature Is Altered in the Cardiac Remodeling Induced by High Fat Diets.

    Science.gov (United States)

    Guedes, Elaine Castilho; França, Gustavo Starvaggi; Lino, Caroline Antunes; Koyama, Fernanda Christtanini; Moreira, Luana do Nascimento; Alexandre, Juliana Gomes; Barreto-Chaves, Maria Luiza M; Galante, Pedro Alexandre Favoretto; Diniz, Gabriela Placoná

    2016-08-01

    Recent studies have revealed the involvement of microRNAs (miRNAs) in the control of cardiac hypertrophy and myocardial function. In addition, several reports have demonstrated that high fat (HF) diet induces cardiac hypertrophy and remodeling. In the current study, we investigated the effect of diets containing different percentages of fat on the cardiac miRNA expression signature. To address this question, male C57Bl/6 mice were fed with a low fat (LF) diet or two HF diets, containing 45 kcal% fat (HF45%) and 60 kcal% fat (HF60%) for 10 and 20 weeks. HF60% diet promoted an increase on body weight, fasting glycemia, insulin, leptin, total cholesterol, triglycerides, and induced glucose intolerance. HF feeding promoted cardiac remodeling, as evidenced by increased cardiomyocyte transverse diameter and interstitial fibrosis. RNA sequencing analysis demonstrated that HF feeding induced distinct miRNA expression patterns in the heart. HF45% diet for 10 and 20 weeks changed the abundance of 64 and 26 miRNAs in the heart, respectively. On the other hand, HF60% diet for 10 and 20 weeks altered the abundance of 27 and 88 miRNAs in the heart, respectively. Bioinformatics analysis indicated that insulin signaling pathway was overrepresented in response to HF diet. An inverse correlation was observed between cardiac levels of GLUT4 and miRNA-29c. Similarly, we found an inverse correlation between expression of GSK3β and the expression of miRNA-21a-3p, miRNA-29c-3p, miRNA-144-3p, and miRNA-195a-3p. In addition, miRNA-1 overexpression prevented cardiomyocyte hypertrophy. Taken together, our results revealed differentially expressed miRNA signatures in the heart in response to different HF diets. J. Cell. Physiol. 231: 1771-1783, 2016. © 2015 Wiley Periodicals, Inc. PMID:26638879

  9. MYOCARDIAL REMODELING IN ISCHEMIC HEART DISEASE

    OpenAIRE

    A.N. Zakirova; R.G. Oganov; N.E. Zakirova; G. R. Klochkova; F.S. Musina

    2016-01-01

    Aim. To study the myocardial remodeling features in patients with stable angina depending on disease severity and experienced myocardial infarction (MI).Material and methods. 148 male patients with stable angina were examined and randomized into 3 groups (G1-G3). 52 patients of G1 had angina of I-II functional class (FC). 49 patients of G2 had angina of III FC, and 47 patients of G3 had angina of IV FC. History of MI had 79,5, 87.2 and 92.6% of patients in G1, G2 and G3 respectively. 35 healt...

  10. Insulin receptor in Drosophila melanogaster

    Energy Technology Data Exchange (ETDEWEB)

    Petruzzelli, L.; Herrera, R.; Rosen, O.

    1986-05-01

    A specific, high affinity insulin receptor is present in both adult Drosophila and in Drosophila embryos. Wheat germ lectin-enriched extracts of detergent-solubilized membranes from embryos and adults bind insulin with a K/sub d/ of 15 nM. Binding is specific for insulin; micromolar concentrations of proinsulin, IGFI, and IGFII are required to displace bound /sup 125/I-insulin. Insulin-dependent protein tyrosine kinase activity appears during embryogenesis. It is evident between 6 and 12 hours of development, peaks between 12 and 18 hours and falls in the adult. During 0-6 hours of embryogenesis, and in the adult, a specific protein band (Mr = 135,000) is crosslinked to /sup 125/I-insulin. During 6-12 and 12-18 hours of embryogenesis stages in which insulin-dependent protein tyrosine kinase is high, an additional band (Mr = 100,000) becomes crosslinked to /sup 125/I-insulin. Isolation and DNA sequence analysis of genomic clones encoding the Drosophila insulin receptor will be presented as will the characterization of insulin receptor mRNA's during development.

  11. Insulin receptor in Drosophila melanogaster

    International Nuclear Information System (INIS)

    A specific, high affinity insulin receptor is present in both adult Drosophila and in Drosophila embryos. Wheat germ lectin-enriched extracts of detergent-solubilized membranes from embryos and adults bind insulin with a K/sub d/ of 15 nM. Binding is specific for insulin; micromolar concentrations of proinsulin, IGFI, and IGFII are required to displace bound 125I-insulin. Insulin-dependent protein tyrosine kinase activity appears during embryogenesis. It is evident between 6 and 12 hours of development, peaks between 12 and 18 hours and falls in the adult. During 0-6 hours of embryogenesis, and in the adult, a specific protein band (Mr = 135,000) is crosslinked to 125I-insulin. During 6-12 and 12-18 hours of embryogenesis stages in which insulin-dependent protein tyrosine kinase is high, an additional band (Mr = 100,000) becomes crosslinked to 125I-insulin. Isolation and DNA sequence analysis of genomic clones encoding the Drosophila insulin receptor will be presented as will the characterization of insulin receptor mRNA's during development

  12. Insulin and insulin mutants stimulate glucose uptake in rat adipocytes

    Institute of Scientific and Technical Information of China (English)

    姚矢音; 张新堂; 许英镐; 张信娜; 朱尚权

    1999-01-01

    A simple method to determine the in vitro biological activity of insulin by measuring glucose uptake in the rat adipocytes is presented here. In the presence of insulin, the glucose uptake is 5-6 times more than the basal control. And the uptake of D-[3-3H]-glucose is linear as the logarithm of insulin concentration from 0.2 μg/L to 1.0 μg/L. Glucose and 3-O-methyl-glucose inhibit D-[3-3H]-glucose uptake into adipocytes. By this method, the in vitro biological activity of [B2-Lys]-insulin and [B3-Lys]-insulin was measured to be 61.6% and 154% respectively, relative to that of insulin.

  13. Aggravated Cardiac Remodeling post Aortocaval Fistula in Unilateral Nephrectomized Rats.

    Directory of Open Access Journals (Sweden)

    Jie Wu

    Full Text Available Aortocaval fistula (AV in rat is a unique model of volume-overload congestive heart failure and cardiac hypertrophy. Living donor kidney transplantation is regarded as beneficial to allograft recipients and not particularly detrimental to the donors. Impact of AV on animals with mild renal dysfunction is not fully understood. In this study, we explored the effects of AV in unilateral nephrectomized (UNX rats.Adult male Sprague-Dawley (SD rats were divided into Sham (n = 10, UNX (right kidney remove, n = 10, AV (AV established between the levels of renal arteries and iliac bifurcation, n = 18 and UNX+AV (AV at one week after UNX, n = 22, respectively. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, fractional excretion of sodium, albuminuria, plasma creatinine, and cystatin C. Focal glomerulosclerosis (FGS incidence was evaluated by renal histology. Cardiac function was measured by echocardiography and hemodynamic measurements.UNX alone induced compensatory left kidney enlargement, increased plasma creatinine and cystatin C levels, and slightly reduced glomerular filtration rate and increased FGS. AV induced significant cardiac enlargement and hypertrophy and reduced cardiac function and increased FGS, these changes were aggravated in UNX+AV rats.Although UNX only induces minor renal dysfunction, additional chronic volume overload placement during the adaptation phase of the remaining kidney is associated with aggravated cardiac dysfunction and remodeling in UNX rats, suggesting special medical care is required for UNX or congenital monokidney subjects in case of chronic volume overload as in the case of pregnancy and hyperthyroidism to prevent further adverse cardiorenal events in these individuals.

  14. Occlusive Peripheral Arterial Disease

    Science.gov (United States)

    ... erythrocyte sedimentation rate (ESR) and level of C-reactive protein, which is produced only when inflammation is present. ... people with occlusive peripheral arterial disease also have coronary artery disease. Amputation of a limb may be necessary if ...

  15. Application of A Microstructural Constitutive Model of the Pulmonary Artery to Patient-Specific Studies: Validation and Effect of Orthotropy

    OpenAIRE

    Zhang, Yanhang; Dunn, Martin L.; Hunter, Kendall S.; Lanning, Craig; Ivy, D. Dunbar; Claussen, Lori; Chen, S. James; Shandas, Robin

    2007-01-01

    We applied a statistical mechanics based microstructural model of pulmonary artery mechanics, developed from our previous studies of rats with pulmonary arterial hypertension (PAH), to patient-specific clinical studies of children with PAH. Our previous animal studies provoked the hypothesis that increased cross-linking density of the molecular chains may be one biological remodeling mechanism by which the PA stiffens in PAH. This study appears to further confirm this hypothesis since varying...

  16. Differential effects of formoterol on thrombin- and PDGF-induced proliferation of human pulmonary arterial vascular smooth muscle cells

    OpenAIRE

    Goncharova Elena A; Khavin Irene S; Goncharov Dmitry A; Krymskaya Vera P

    2012-01-01

    Abstract Background Increased pulmonary arterial vascular smooth muscle (PAVSM) cell proliferation is a key pathophysiological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PH). The long-acting β2-adrenergic receptor (β2AR) agonist formoterol, a racemate comprised of (R,R)- and (S,S)-enantiomers, is commonly used as a vasodilator in chronic obstructive pulmonary disease (COPD). PH, a common complication of COPD, increases patients’ morbidity and reduces surviv...

  17. Differential effects of formoterol on thrombin- and PDGF-induced proliferation of human pulmonary arterial vascular smooth muscle cells

    OpenAIRE

    Goncharova, Elena A.; Khavin, Irene S; Goncharov, Dmitry A; Vera P Krymskaya

    2012-01-01

    Background Increased pulmonary arterial vascular smooth muscle (PAVSM) cell proliferation is a key pathophysiological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PH). The long-acting β2-adrenergic receptor (β2AR) agonist formoterol, a racemate comprised of (R,R)- and (S,S)-enantiomers, is commonly used as a vasodilator in chronic obstructive pulmonary disease (COPD). PH, a common complication of COPD, increases patients’ morbidity and reduces survival. Recen...

  18. Inhaled tolafentrine reverses pulmonary vascular remodeling via inhibition of smooth muscle cell migration

    Directory of Open Access Journals (Sweden)

    Weissmann Norbert

    2005-11-01

    Full Text Available Abstract Background The aim of the study was to assess the chronic effects of combined phosphodiesterase 3/4 inhibitor tolafentrine, administered by inhalation, during monocrotaline-induced pulmonary arterial hypertension (PAH in rats. Methods CD rats were given a single subcutaneous injection of monocrotaline to induce PAH. Four weeks after, rats were subjected to inhalation of tolafentrine or sham nebulization in an unrestrained, whole body aerosol exposure system. In these animals (i the acute pulmonary vasodilatory efficacy of inhaled tolafentrine (ii the anti-remodeling effect of long-term inhalation of tolafentrine (iii the effects of tolafentrine on the expression profile of 96 genes encoding cell adhesion and extracellular matrix regulation were examined. In addition, the inhibitory effect of tolafentrine on ex vivo isolated pulmonary artery SMC cell migration was also investigated. Results Monocrotaline injection provoked severe PAH (right ventricular systolic pressure increased from 25.9 ± 4.0 to 68.9 ± 3.2 after 4 weeks and 74.9 ± 5.1 mmHg after 6 weeks, cardiac output depression and right heart hypertrophy. The media thickness of the pulmonary arteries and the proportion of muscularization of small precapillary resistance vessels increased dramatically, and the migratory response of ex-vivo isolated pulmonary artery smooth muscle cells (PASMC was increased. Micro-arrays and subsequent confirmation with real time PCR demonstrated upregulation of several extracellular matrix regulation and adhesion genes, such as matrixmetalloproteases (MMP 2, 8, 9, 10, 11, 12, 20, Icam, Itgax, Plat and serpinb2. When chronically nebulized from day 28 to 42 (12 daily aerosol maneuvers, after full establishment of severe pulmonary hypertension, tolafentrine reversed about 60% of all hemodynamic abnormalities, right heart hypertrophy and monocrotaline-induced structural lung vascular changes, including the proportion of pulmonary artery

  19. Combination of Rare Right Arterial Variation with Anomalous Origins of the Vertebral Artery, Aberrant Subclavian Artery and Persistent Trigeminal Artery

    Science.gov (United States)

    Ishihara, H.; San Millán Ruíz, D.; Abdo, G.; Asakura, F.; Yilmaz, H.; Lovblad, K.O.; Rüfenacht, D.A.

    2011-01-01

    Summary A 32-year-old woman hospitalized for subarachnoid hemorrhage showed rare arterial variation on the right side with anomalous origins of the vertebral artery, aberrant subclavian artery and persistent trigeminal artery. Angiography showed the right vertebral artery to originate from the right common carotid artery, the right subclavian artery to arise separately from the descending aorta, and persistent trigeminal artery on the right side. The possible embryonic mechanism of this previously unreported variant combination is discussed. PMID:22005696

  20. On Renal Artery Stenosis

    OpenAIRE

    Eklöf, Hampus

    2005-01-01

    Renal artery stenosis (RAS) is a potentially curable cause of hypertension and azotemia. Besides intra-arterial renal angiography there are several non-invasive techniques utilized to diagnose patients with suspicion of renal artery stenosis. Removing the stenosis by revascularization to restore unobstructed blood flow to the kidney is known to improve and even cure hypertension/azotemia, but is associated with a significant complication rate. To visualize renal arteries with x-ray technique...

  1. The reversal of pulmonary vascular remodeling through inhibition of p38 MAPK-alpha: a potential novel anti-inflammatory strategy in pulmonary hypertension

    OpenAIRE

    Church, Alistair C.; Martin, Damien H.; Wadsworth, Roger; Bryson, Gareth; Fisher, Andrew J.; Welsh, David J.; Peacock, Andrew J

    2015-01-01

    The p38 mitogen-activated protein kinase (MAPK) system is increasingly recognized as an important inflammatory pathway in systemic vascular disease but its role in pulmonary vascular disease is unclear. Previous in vitro studies suggest p38 MAPKα is critical in the proliferation of pulmonary artery fibroblasts, an important step in the pathogenesis of pulmonary vascular remodeling (PVremod). In this study the role of the p38 MAPK pathway was investigated in both in vitro and in vivo models of...

  2. Expression of peptide fragments from proADM and involvement of mitogen-activated protein kinase signaling pathways in pulmonary remodeling induced by high pulmonary blood flow.

    Science.gov (United States)

    Li, Wei; Guo, Aili; Wang, Lijuan; Kong, Qingyu; Wang, Rong; Han, Li; Zhao, Cuifen

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by progressive pulmonary arterial remodeling and right ventricular failure. Despite recent advances in pathophysiological mechanism exploration and new therapeutic approaches, PAH remains a challenging condition. In this study, we investigated the roles of the peptide fragments from proadrenomedullin (proADM) such as adrenomedullin (ADM), adrenotensin (ADT), and proadrenomedullin N-terminal 20 peptide (PAMP) during pulmonary remodeling caused by high pulmonary blood flow, and probed the possible involvement of mitogen-activated protein kinase (MAPK) signal transduction pathways. Sixteen rat models of PAH were artificially established by surgically connecting the left common carotid artery to the external jugular vein. We subcutaneously injected an extracellular signal-regulated protein kinase (ERK1/2) inhibitor, PD98059, in eight rats, treated another eight rats with an equal volume of saline. Eight rats without connections served as the control group. We observed that mRNA expression levels of ADM, stress-activated protein kinase (SAPK), and ERK1/2 were significantly elevated in the shunted rats; furthermore, ERK1/2 levels were significantly inhibited by PD98059. Protein levels of ADM, PAMP, p-SAPK, and p-ERK1/2 were significantly higher ADT was lower, and p-p38 remained unchanged in the rat models compared with the controls. However, the protein expression of both ADM and p-ERK1/2 was significantly inhibited by PD98059. Our results suggest that levels of ADM, ADT, and PAMP respond to pulmonary remodeling, and that activation of the SAPK and ERK1/2 signaling pathways is involved in pulmonary hypertension and artery remodeling caused by high pulmonary blood flow. PMID:25990643

  3. Estimation of pulmonary arterial volume changes in the normal and hypertensive fawn-hooded rat from 3D micro-CT data

    Science.gov (United States)

    Molthen, Robert C.; Wietholt, Christian; Haworth, Steven T.; Dawson, Christopher A.

    2002-04-01

    In the study of pulmonary vascular remodeling, much can be learned from observing the morphological changes undergone in the pulmonary arteries of the rat lung when exposed to chronic hypoxia or other challenges which elicit a remodeling response. Remodeling effects include thickening of vessel walls, and loss of wall compliance. Morphometric data can be used to localize the hemodynamic and functional consequences. We developed a CT imaging method for measuring the pulmonary arterial tree over a range of pressures in rat lungs. X-ray micro-focal isotropic volumetric imaging of the arterial tree in the intact rat lung provides detailed information on the size, shape and mechanical properties of the arterial network. In this study, we investigate the changes in arterial volume with step changes in pressure for both normoxic and hypoxic Fawn-Hooded (FH) rats. We show that FH rats exposed to hypoxia tend to have reduced arterial volume changes for the same preload when compared to FH controls. A secondary objective of this work is to quantify various phenotypes to better understand the genetic contribution of vascular remodeling in the lungs. This volume estimation method shows promise in high throughput phenotyping, distinguishing differences in the pulmonary hypertensive rat model.

  4. Selective intra-arterial calcium stimulation with hepatic venous sampling for preoperative localization of insulinomas

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Yon Mi; Do, Young Soo; Lee, Moon Kyu; Shin, Sung Wook; Liu, Wei Chiang; Choo; Sung Wook; Choo, In wook [Sungkyunkwan University School of Mecidine, Seoul (Korea, Republic of)

    2003-06-01

    To determine the value of selective intra-arterial calcium stimulation with hepatic venous sampling using serum insulin and C-peptide gradients for the preoperative localization of insulinomas. Seven consecutive patients [three men and four women aged 15-77 (mean, 42.7) years] with hypoglycemia underwent selective intra-arterial calcium stimulation in conjunction with hepatic venous sampling. Insulin gradients were calculated by an individual blinded to all other preoperative imaging studies and operative findings. In all patients except one, C-peptide gradients were also analyzed. The results were compared with the preoperative findings of ultrasonography, computed tomography, arteriography and endoscopic ultrasonography, as well as with the intraoperative findings of ultrasonography and palpation at surgery. Eight insulinomas (mean diameter, 12.5 mm) were diagnosed after surgery. In six patients, the calcium stimulation test with insulin gradients allowed accurate localization of the pathologic source of insulin secretion. Both C-peptide and insulin gradients substantially increased diagnostic accuracy. In one patient, C-peptide gradients were more helpful than insulin gradients for tumor localization. Selective intra-arterial calcium stimulation with hepatic venous sampling is a highly accurate and safe method for the preoperative localization of insulinomas. Additional C-peptide gradients seem be helpful in assessing tumor location, but further study is needed.

  5. Selective intra-arterial calcium stimulation with hepatic venous sampling for preoperative localization of insulinomas

    International Nuclear Information System (INIS)

    To determine the value of selective intra-arterial calcium stimulation with hepatic venous sampling using serum insulin and C-peptide gradients for the preoperative localization of insulinomas. Seven consecutive patients [three men and four women aged 15-77 (mean, 42.7) years] with hypoglycemia underwent selective intra-arterial calcium stimulation in conjunction with hepatic venous sampling. Insulin gradients were calculated by an individual blinded to all other preoperative imaging studies and operative findings. In all patients except one, C-peptide gradients were also analyzed. The results were compared with the preoperative findings of ultrasonography, computed tomography, arteriography and endoscopic ultrasonography, as well as with the intraoperative findings of ultrasonography and palpation at surgery. Eight insulinomas (mean diameter, 12.5 mm) were diagnosed after surgery. In six patients, the calcium stimulation test with insulin gradients allowed accurate localization of the pathologic source of insulin secretion. Both C-peptide and insulin gradients substantially increased diagnostic accuracy. In one patient, C-peptide gradients were more helpful than insulin gradients for tumor localization. Selective intra-arterial calcium stimulation with hepatic venous sampling is a highly accurate and safe method for the preoperative localization of insulinomas. Additional C-peptide gradients seem be helpful in assessing tumor location, but further study is needed

  6. [Intensified insulin therapy and insulin micro-pumps during pregnancy].

    Science.gov (United States)

    Galuppi, V

    1994-06-01

    Before conception and during pregnancy in diabetic patients, every possible effort should be made in order to obtain a good, if not perfect, metabolic control and to warrant maternal and fetal health. Multiple daily injections are required to achieve a very strict glucose regulation in pregnant patients with insulin-dependent diabetes mellitus. The most usual intensive insulin administration patterns require 3 premeal doses of short-acting insulin and 1 (at bedtime) or 2 (one in the morning and one at bedtime) injections of intermediate or slow-acting insulin. As an alternative choice, insulin pumps allow a continuous subcutaneous infusion with short-acting insulin according to a basal rate which cover the insulin need during the night and between meals. Premeal and presnack surges of insulin are administrated by the patient herself. Home glucose monitoring must be used to adjust insulin doses. Target glucose levels every diabetic pregnant woman should try to achieve are lower than in non-pregnant women: fasting glycaemia should be below 100 mg/dl, 1 hour post-prandial value below 140 mg/dl and 2 hour post-prandial level below 120 mg/dl. The stricter the control and treatment goals are, the more frequently hypoglycaemia may occur. Hypoglycaemia may be harmful especially for patients with severe diabetic complications and may affect the fetus. Therefore, every pregnant diabetic woman should receive individualized treatment and glycaemic goals according to her clinical features, her compliance and her social and cultural background. PMID:7968932

  7. Peripheral Artery Disease

    Science.gov (United States)

    ... or atherectomy may be used to help improve blood flow. What is peripheral artery disease (PAD)? How is peripheral artery disease evaluated? How ... PAD are diabetes, smoking, high cholesterol and high blood pressure. Most cases occur in ... is peripheral artery disease evaluated? Several imaging tests can be used to ...

  8. Retinal artery occlusion

    Science.gov (United States)

    ... artery occlusion; Branch retinal artery occlusion; CRAO; BRAO Images Retina References Sanborn GE, Magargal LE. Arterial obstructive disease ... A.M. Editorial team. Related MedlinePlus Health Topics ... audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among ...

  9. Abnormal bone remodelling in inflammatory arthritis

    Science.gov (United States)

    Bogoch, Earl R.; Moran, Erica

    1998-01-01

    Osteopenia is responsible for substantial comorbidity in patients suffering from rheumatoid arthritis and is an important factor in the surgical management of joint disease. In animal models of bone loss stimulated by inflammatory arthritis, increased bone remodelling and altered microstructure of bone have been documented. The subchondral bone plate near the joint surface is narrow and perforated by vascular inflammatory invasion, and in the shaft the thin cortices are weakened by giant resorption defects. Biomechanical tests and a mathematical model of bone strength suggest that cortical defects, much larger than those found in normal osteonal remodelling, are principally responsible for the experimentally observed loss of strength. Similarly, these defects may explain the increased femoral fracture risk in rheumatoid arthritis. The osteoclast, the cell resorbing bone, is demonstrated in increased number and activity in rheumatoid arthritis and in animal models. Bisphosphonates, drugs that inhibit osteoclast function, have been shown experimentally to reduce both focal and generalized osteopenia and to prevent loss of bone strength. Bisphosphonates also protect articular cartilage from damage characteristic of inflammatory arthritis. The mechanism of chondroprotection may be prevention of subchondral bone resorption by the osteoclast and also an altered distribution of bone marrow cells. Thus, bisphosphonates, currently in clinical use for other bone metabolic diseases, appear to have potential as prophylaxis and treatment for osteopenia and joint damage in inflammatory arthritis. PMID:9711159

  10. Histamine in regulation of bone remodeling processes

    Directory of Open Access Journals (Sweden)

    Marek Wiercigroch

    2013-08-01

    Full Text Available Bone remodeling is under autocrine, paracrine, endocrine and central nervous system control. One of the potential endogenous factors affecting bone remodeling is histamine, an endogenous amine which acts as a mediator of allergic reactions and neuromediator, and induces production of gastric acid. Histamine H1 receptor antagonists are widely used in the treatment of allergic conditions, H2 receptor antagonists in peptic ulcer disease, and betahistine (an H3 receptor antagonist and H1 receptor agonist is used in the treatment of Ménière’s disease.Excess histamine release in mastocytosis and allergic diseases may lead to development of osteoporosis. Clinical and population-based studies on the effects of histamine receptor antagonists on the skeletal system have not delivered unequivocal results.Expression of mRNA of histamine receptors has been discovered in bone cells (osteoblasts and osteoclasts. Histamine synthesis has been demonstrated in osteoclast precursors. Histamine increases bone resorption both by direct effects on osteoclast precursors and osteoclasts, and indirectly, by increasing the expression of RANKL in osteoblasts. In in vivo studies, H1 and H2 receptor antagonists exerted protective effects on the bone tissue, although not in all experimental models. In the present article, in vitro and in vivo studies conducted so far, concerning the effects of histamine and drugs modifying its activity on the skeletal system, have been reviewed.

  11. [Histamine in regulation of bone remodeling processes].

    Science.gov (United States)

    Wiercigroch, Marek; Folwarczna, Joanna

    2013-01-01

    Bone remodeling is under autocrine, paracrine, endocrine and central nervous system control. One of the potential endogenous factors affecting bone remodeling is histamine, an endogenous amine which acts as a mediator of allergic reactions and neuromediator, and induces production of gastric acid. Histamine H₁ receptor antagonists are widely used in the treatment of allergic conditions, H₂ receptor antagonists in peptic ulcer disease, and betahistine (an H₃ receptor antagonist and H₁ receptor agonist) is used in the treatment of Ménière's disease. Excess histamine release in mastocytosis and allergic diseases may lead to development of osteoporosis. Clinical and population-based studies on the effects of histamine receptor antagonists on the skeletal system have not delivered unequivocal results. Expression of mRNA of histamine receptors has been discovered in bone cells (osteoblasts and osteoclasts). Histamine synthesis has been demonstrated in osteoclast precursors. Histamine increases bone resorption both by direct effects on osteoclast precursors and osteoclasts, and indirectly, by increasing the expression of RANKL in osteoblasts. In in vivo studies, H₁ and H₂ receptor antagonists exerted protective effects on the bone tissue, although not in all experimental models. In the present article, in vitro and in vivo studies conducted so far, concerning the effects of histamine and drugs modifying its activity on the skeletal system, have been reviewed. PMID:24018454

  12. Epithelial Cell Apoptosis and Lung Remodeling

    Institute of Scientific and Technical Information of China (English)

    Kazuyoshi Kuwano

    2007-01-01

    Lung epithelium is the primary site of lung damage in various lung diseases. Epithelial cell apoptosis has been considered to be initial event in various lung diseases. Apoptosis signaling is classically composed of two principle pathways. One is a direct pathway from death receptor ligation to caspase cascade activation and cell death. The other pathway triggered by stresses such as drugs, radiation, infectious agents and reactive oxygen species is mediated by mitochondria. Endoplasmic reticulum has also been shown to be the organelle to mediate apoptosis.Epithelial cell death is followed by remodeling processes, which consist of epithelial and fibroblast activation,cytokine production, activation of coagulation pathway, neoangiogenesis, re-epithelialization and fibrosis.Epithelial and mesenchymal interaction plays important roles in these processes. Further understanding of apoptosis signaling and its regulation by novel strategies may lead to effective treatments against various lung diseases. We review the recent advances in the understanding of apoptosis signaling and discuss the involvement of apoptosis in lung remodeling.

  13. Atrial remodeling, fibrosis, and atrial fibrillation.

    Science.gov (United States)

    Jalife, José; Kaur, Kuljeet

    2015-08-01

    The fundamental mechanisms governing the perpetuation of atrial fibrillation (AF), the most common arrhythmia seen in clinical practice, are poorly understood, which explains in part why AF prevention and treatment remain suboptimal. Although some clinical parameters have been identified as predicting a transition from paroxysmal to persistent AF in some patients, the molecular, electrophysiological, and inflammation changes leading to such a progression have not been described in detail. Oxidative stress, atrial dilatation, calcium overload, inflammation, microRNAs, and myofibroblast activation are all thought to be involved in AF-induced atrial remodeling. However, it is unknown to what extent and at which time points such alterations influence the remodeling process that perpetuates AF. Here we postulate a working model that might open new pathways for future investigation into mechanisms of AF perpetuation. We start from the premise that the progression to AF perpetuation is the result of interplay among manifold signaling pathways with differing kinetics. Some such pathways have relatively fast kinetics (e.g., oxidative stress-mediated shortening of refractory period); others likely depend on molecular processes with slower kinetics (e.g., transcriptional changes in myocyte ion channel protein expression mediated through inflammation and fibroblast activation). We stress the need to fully understand the relationships among such pathways should one hope to identify novel, truly effective targets for AF therapy and prevention. PMID:25661032

  14. Sox17 is indispensable for acquisition and maintenance of arterial identity

    Science.gov (United States)

    Corada, Monica; Orsenigo, Fabrizio; Morini, Marco Francesco; Pitulescu, Mara Elena; Bhat, Ganesh; Nyqvist, Daniel; Breviario, Ferruccio; Conti, Valentina; Briot, Anais; Iruela-Arispe, M. Luisa; Adams, Ralf H.; Dejana, Elisabetta

    2013-10-01

    The functional diversity of the arterial and venous endothelia is regulated through a complex system of signalling pathways and downstream transcription factors. Here we report that the transcription factor Sox17, which is known as a regulator of endoderm and hemopoietic differentiation, is selectively expressed in arteries, and not in veins, in the mouse embryo and in mouse postnatal retina and adult. Endothelial cell-specific inactivation of Sox17 in the mouse embryo is accompanied by a lack of arterial differentiation and vascular remodelling that results in embryo death in utero. In mouse postnatal retina, abrogation of Sox17 expression in endothelial cells leads to strong vascular hypersprouting, loss of arterial identity and large arteriovenous malformations. Mechanistically, Sox17 acts upstream of the Notch system and downstream of the canonical Wnt system. These data introduce Sox17 as a component of the complex signalling network that orchestrates arterial/venous specification.

  15. Insulin Degludec, The New Generation Basal Insulin or Just another Basal Insulin?

    Science.gov (United States)

    Nasrallah, Sami N; Reynolds, L Raymond

    2012-01-01

    The advances in recombinant DNA technology have led to an improvement in the properties of currently available long-acting insulin analogs. Insulin degludec, a new generation ultra-long-acting basal insulin, currently in phase 3 clinical trials, has a promising future in clinical use. When compared to its rival basal insulin analogs, a longer duration of action and lower incidence of hypoglycemic events in both type 1 and type 2 diabetic patients has been demonstrated.1,2 Its unique mechanism of action is based on multihexamer formation after subcutaneous injection. This reportedly allows for less pharmacodynamic variability and within-subject variability than currently available insulin analogs, and a duration of action that is over 24 hours.3 The lack of proof of carcinogenicity with insulin degludec is yet another factor that would be taken into consideration when choosing the optimal basal insulin for a diabetic individual.4 A formulation of insulin degludec with insulin aspart, Insulin degludec 70%/aspart 30%, may permit improved flexibly of dosing without compromising glycemic control or safety.5. PMID:22879797

  16. Roles of Caveolin-1 in Angiotensin II-Induced Hypertrophy and Inward Remodeling of Cerebral Pial Arterioles.

    Science.gov (United States)

    Umesalma, Shaikamjad; Houwen, Frederick Keith; Baumbach, Gary L; Chan, Siu-Lung

    2016-03-01

    Angiotensin II (Ang II) is a major determinant of inward remodeling and hypertrophy in pial arterioles that may have an important role in stroke during chronic hypertension. Previously, we found that epidermal growth factor receptor is critical in Ang II-mediated hypertrophy that may involve caveolin-1 (Cav-1). In this study, we examined the effects of Cav-1 and matrix metalloproteinase-9 (MMP9) on Ang II-mediated structural changes in pial arterioles. Cav-1-deficient (Cav-1(-/-)), MMP9-deficient (MMP9(-/-)), and wild-type mice were infused with either Ang II (1000 ng/kg per minute) or saline via osmotic minipumps for 28 days (n=6-8 per group). Systolic arterial pressure was measured by a tail-cuff method. Pressure and diameter of pial arterioles were measured through an open cranial window in anesthetized mice. Cross-sectional area of the wall was determined histologically in pressurized fixed pial arterioles. Expression of Cav-1, MMP9, phosphorylated epidermal growth factor receptor, and Akt was determined by Western blotting and immunohistochemistry. Deficiency of Cav-1 or MMP9 did not affect Ang II-induced hypertension. Ang II increased the expression of Cav-1, phosphorylated epidermal growth factor receptor, and Akt in wild-type mice, which was attenuated in Cav-1(-/-) mice. Ang II-induced hypertrophy, inward remodeling, and increased MMP9 expression in pial arterioles were prevented in Cav-1(-/-) mice. Ang II-mediated increases in MMP9 expression and inward remodeling, but not hypertrophy, were prevented in MMP9(-/-) mice. In conclusion, Cav-1 is essential in Ang II-mediated inward remodeling and hypertrophy in pial arterioles. Cav-1-induced MMP9 is exclusively involved in inward remodeling, not hypertrophy. Further studies are needed to determine the role of Akt in Ang II-mediated hypertrophy. PMID:26831194

  17. Gestational Diabetes Mellitus: Insulinic Management

    OpenAIRE

    Magon, Navneet; Seshiah, Veerasamy

    2014-01-01

    Diabetic pregnancies have attendant risks. Adverse fetal, neonatal, and maternal outcomes in a diabetic pregnancy can be avoided by optimum glycemic control. Most pregnancies with GDM can be managed with non-insulinic management, which includes medical nutrition therapy. However, many necessitate concomitant insulinic management. The new insulin analogs present undoubted advantages in reducing the risk of hypoglycemia, mainly during the night, and in promoting a more physiologic glycemic prof...

  18. Protein Crystal Recombinant Human Insulin

    Science.gov (United States)

    1994-01-01

    The comparison of protein crystal, Recombiant Human Insulin; space-grown (left) and earth-grown (right). On STS-60, Spacehab II indicated that space-grown crystals are larger and of greater optical clarity than their earth-grown counterparts. Recombiant Human Insulin facilitates the incorporation of glucose into cells. In diabetics, there is either a decrease in or complete lack of insulin, thereby leading to several harmful complications. Principal Investigator is Larry DeLucas.

  19. Cell factories for insulin production

    OpenAIRE

    Baeshen, Nabih A.; Baeshen, Mohammed N; Sheikh, Abdullah; Bora, Roop S; Mohamed Morsi M. Ahmed; Ramadan, Hassan A I; Saini, Kulvinder Singh; Redwan, Elrashdy M.

    2014-01-01

    The rapid increase in the number of diabetic patients globally and exploration of alternate insulin delivery methods such as inhalation or oral route that rely on higher doses, is bound to escalate the demand for recombinant insulin in near future. Current manufacturing technologies would be unable to meet the growing demand of affordable insulin due to limitation in production capacity and high production cost. Manufacturing of therapeutic recombinant proteins require an appropriate host org...

  20. Nutritional Modulation of Insulin Resistance

    OpenAIRE

    Weickert, Martin O.

    2012-01-01

    Insulin resistance has been proposed as the strongest single predictor for the development of Type 2 Diabetes (T2DM). Chronic oversupply of energy from food, together with inadequate physical activity, have been recognized as the most relevant factors leading to overweight, abdominal adiposity, insulin resistance, and finally T2DM. Conversely, energy reduced diets almost invariably to facilitate weight loss and reduce abdominal fat mass and insulin resistance. However, sustained weight loss i...

  1. Dual neural endopeptidase/endothelin-converting [corrected] enzyme inhibition improves endothelial function in mesenteric resistance arteries of young spontaneously hypertensive rats

    DEFF Research Database (Denmark)

    Lemkens, Pieter; Nelissen, Jelly; Meens, Merlijn J P M T;

    2012-01-01

    through cleavage of big ET1 by endothelin-converting enzyme (ECE) and neutral endopeptidase (NEP). METHOD: We investigated whether the dual NEP/ECE inhibitor SOL1 improves resistance artery function and structure in 12 weeks old spontaneously hypertensive rats (SHRs) and whether arterial structural...... impaired in SHRs. Chronic SOL1 treatment did not restore this response. CONCLUSION: Thus chronic SOL1 treatment during the development of hypertension in SHRs has no effect on blood pressure but improves several aspects of endothelium-dependent vasomotor responses but not arterial remodeling.......BACKGROUND: Endothelin-1 (ET1) is a potent vasoconstrictor peptide with pro-mitogenic and pro-inflammatory properties and is therefore of interest in the development of endothelial dysfunction, endothelium-dependent flow-related remodeling, and hypertension-related remodeling. ET1 can be formed...

  2. Ventricular structure, function, and mechanics at high altitude: chronic remodeling in Sherpa vs. short-term lowlander adaptation

    OpenAIRE

    Stembridge, Mike; Ainslie, Philip N; Hughes, Michael G.; Stöhr, Eric J.; Cotter, James D.; Nio, Amanda Q. X.; Shave, Rob

    2014-01-01

    Short-term, high-altitude (HA) exposure raises pulmonary artery systolic pressure (PASP) and decreases left-ventricular (LV) volumes. However, relatively little is known of the long-term cardiac consequences of prolonged exposure in Sherpa, a highly adapted HA population. To investigate short-term adaptation and potential long-term cardiac remodeling, we studied ventricular structure and function in Sherpa at 5,050 m (n = 11; 31 ± 13 yr; mass 68 ± 10 kg; height 169 ± 6 cm) and lowlanders at s...

  3. Impact of Drug-Eluting Stents Among Insulin-Treated Diabetic Patients A Report from the NHLBI Dynamic Registry

    Science.gov (United States)

    Mulukutla, Suresh R.; Vlachos, Helen A.; Marroquin, Oscar C.; Selzer, Faith; Holper, Elizabeth M.; Abbott, J. Dawn; Laskey, Warren K.; Williams, David O.; Smith, Conrad; Anderson, William D.; Lee, Joon S.; Srinivas, Vankeepuram; Kelsey, Sheryl F.; Kip, Kevin E.

    2009-01-01

    Objective To evaluate the safety and efficacy of drug-eluting stents (DES) compared with bare metal stents (BMS) in patients with insulin-treated and non-insulin-treated diabetes. Background Diabetes is a powerful predictor of adverse events following percutaneous coronary interventions (PCI), and insulin-treated diabetic patients have worse outcomes. DES are efficacious among patients with diabetes; however, their safety and efficacy, compared to BMS, among insulin-treated versus non-insulin-treated diabetic patients is not well established. Methods Using the NHLBI Dynamic Registry, we evaluated 1-year outcomes of insulin-treated (n=817) and non-insulin-treated (n=1749) patients with diabetes who underwent PCI with DES versus BMS. Results The use of DES, compared to BMS, was associated with a lower risk for repeat revascularization for both non-insulin-treated patients (adjusted HR=0.59, 95% CI 0.45–0.76) and insulin-treated subjects (adjusted HR=0.63, 95% CI 0.44–0.90). With respect to safety in the overall diabetic population, DES use was associated with a reduction of death or MI (adjusted HR=0.75, 95% CI 0.58–0.96). However, this benefit was confined to the population of non-insulin-treated patients (adjusted HR=0.57, 95% CI 0.41–0.81). Among insulin-treated patients, there was no difference in death or MI risk between DES- and BMS-treated patients (adjusted HR=0.95, 95% CI 0.65–1.39). Conclusions Drug-eluting stents are associated with lower risk for repeat revascularization compared with BMS in treating coronary artery disease among patients with either insulin-treated or non-insulin-treated diabetes. In addition, DES use is not associated with any significant increased safety risk compared to BMS. These findings suggest that DES should be the preferred strategy for diabetic patients. CONDENSED ABSTRACT Insulin-treated patients with diabetes mellitus have worse outcomes following percutaneous coronary intervention (PCI) compared with non-insulin

  4. Straining mode-dependent collagen remodeling in engineered cardiovascular tissue

    NARCIS (Netherlands)

    Rubbens, M.P.; Mol, A.; Marion, M.H. van; Hanemaaijer, R.; Bank, R.A.; Baaijens, F.P.T.; Bouten, C.V.C.

    2009-01-01

    Similar to native cardiovascular tissues, the mechanical properties of engineered cardiovascular constructs depend on the composition and quality of the extracellular matrix, which is a net result of matrix remodeling processes within the tissue. To improve tissue remodeling, and hence tissue mechan

  5. Duplication of hepatic artery

    Directory of Open Access Journals (Sweden)

    Saeed Muhammad

    2001-01-01

    Full Text Available Background: The hepatic arterial anatomy is aberrant in almost 33-41% of individuals. The variant arterial anatomy recognized during routine cadaveric dissection offers great learning potential. Such findings provide an alternative perspective to view common morphology and its structural and functional importance. These impart the concept of patient individuality and subsequent individualization of medical and surgical therapies. Adequate knowledge of normal and abnormal arterial anatomy is essential for peripancreatic surgery and liver transplantation. Aims of the study: To report on hepatic artery variations observed in the dissecting room and to find out the macroscopic pattern of varied human hepatic arterial vascularization by cadaveric dissection. Patients and Methods: Twenty human cadavers of caucasian origin were dissected to study the source and topographic pattern of hepatic arterial supply. Results: Nineteen cadavers exhibited typical hepatic arterial supply from the celiac axis. Only one female body out of twenty cadavers exhibited a dual arterial supply to all parts of liver and gallbladder. One artery originated from the celiac axis whereas the other was given off by the superior mesenteric artery. Conclusion: No doubt, aberrant hepatic vascularization should be assessed preoperatively by invasive and noninvasive techniques to avoid fatal complications, but we favour careful dissection over angiography as a means of defining the arterial anatomy.

  6. Impaired dopamine D1 receptor-mediated vasorelaxation of mesenteric arteries in obese Zucker rats

    OpenAIRE

    Fu, Jinjuan; Han, Yu; Wang, Hongyong; Wang, Zhen; Liu, Yukai; Chen, Xingjian; Cai, Yue; Guan, Weiwei; Yang, Di; Asico, Laureano D.; ZHOU, Lin; Jose, Pedro A; Zeng, Chunyu

    2014-01-01

    Background Obesity plays an important role in the pathogenesis of hypertension. Renal dopamine D1-like receptor-mediated diuresis and natriuresis are impaired in the obese Zucker rat, an obesity-related hypertensive rat model. The role of arterial D1 receptors in the hypertension of obese Zucker rats is not clear. Methods Plasma glucose and insulin concentrations and blood pressure were measured. The vasodilatory response of isolated mesenteric arteries was evaluated using a small vessel myog...

  7. Phenylacetic acid and arterial vascular properties in patients with chronic kidney disease stage 5 on hemodialysis therapy

    DEFF Research Database (Denmark)

    Scholze, Alexandra; Jankowski, Vera; Henning, Lars;

    2007-01-01

    Phenylacetic acid (PAA) is a recently described uremic toxin that inhibits inducible nitric oxide synthase expression and plasma membrane calcium ATPase and may therefore also be involved in remodeling of arteries. Such vascular effects have not been evaluated yet in patients with chronic kidney...... disease stage 5....

  8. Acute occlusion of the left subclavian artery with artery dissection

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Subclavian steal syndrome is cerebral or brain stem ischemia resulting from diversion of blood flow from the basilar artery to the subclavian artery, which is caused by occlusive disease of either the subclavian artery or the innominate artery before they branch off at the vertebral artery. In the patients with subclavian steal syndrome the subclavian artery is fed by retrograde flow from the vertebral artery via the carotids and the circle of Willis.

  9. Human insulin prepared by recombinant DNA techniques and native human insulin interact identically with insulin receptors.

    OpenAIRE

    Keefer, L M; Piron, M A; DE MEYTS, P.

    1981-01-01

    Human insulin synthesized from A and B chains separately produced in Escherichia coli from cloned synthetic genes (prepared by the Eli Lilly Research Laboratories, Indianapolis, IN) was characterized by examining its interaction with human cultured lymphocytes, human circulating erythrocytes in vitro, and isolated rat fat cells. The binding behavior of the biosynthetic insulin with human cells was indistinguishable from that of native human or porcine insulins, with respect to affinity, assoc...

  10. SIRT2 regulates insulin sensitivity in insulin resistant neuronal cells.

    Science.gov (United States)

    Arora, Amita; Dey, Chinmoy Sankar

    2016-06-10

    Insulin resistance in brain is well-associated with pathophysiology of deficits in whole-body energy metabolism, neurodegenerative diseases etc. Among the seven sirtuins, SIRT2 is the major deacetylase expressed in brain. Inhibition of SIRT2 confers neuroprotection in case of Parkinson's disease (PD) and Huntington's disease (HD). However, the role of this sirtuin in neuronal insulin resistance is not known. In this study, we report the role of SIRT2 in regulating insulin-sensitivity in neuronal cells in vitro. Using approaches like pharmacological inhibition of SIRT2, siRNA mediated SIRT2 knockdown and over-expression of wild-type and catalytically-mutated SIRT2, we observed that downregulation of SIRT2 ameliorated the reduced activity of AKT and increased insulin-stimulated glucose uptake in insulin resistant neuro-2a cells. The data was supported by over expression of catalytically-inactive SIRT2 in insulin-resistant human SH-SY5Y neuronal cells. Data highlights a crucial role of SIRT2 in regulation of neuronal insulin sensitivity under insulin resistant condition. PMID:27163642

  11. Improved insulin sensitivity after exercise: focus on insulin signaling

    DEFF Research Database (Denmark)

    Frøsig, Christian; Richter, Erik

    2009-01-01

    After a single bout of exercise, the ability of insulin to stimulate glucose uptake is markedly improved locally in the previously active muscles. This makes exercise a potent stimulus counteracting insulin resistance characterizing type 2 diabetes (T2D). It is believed that at least part of the ...

  12. Monoclonal antibodies to the human insulin receptor block insulin binding and inhibit insulin action.

    OpenAIRE

    Roth, R A; Cassell, D J; Wong, K. Y.; Maddux, B A; Goldfine, I D

    1982-01-01

    Antibodies to the insulin receptor were prepared in BALB/c mice by immunization with IM-9 human lymphocytes, a cell type that has a large number of plasma membrane insulin receptors. The spleens of these mice were then removed, and their lymphocytes were fused to a mouse myeloma cell line, FO cells. After screening over 1,200 resulting hybrids, one stable hybrid was obtained that produced IgG1 antibodies directed towards the insulin receptor. This antibody blocked 125I-labeled insulin binding...

  13. Total adiponectin and adiponectin multimeric complexes in relation to weight loss-induced improvements in insulin sensitivity in obese women

    DEFF Research Database (Denmark)

    Polak, J.; Kovacova, Z.; Holst, C.;

    2008-01-01

    AIM: Adiponectin increases insulin sensitivity, protects arterial walls against atherosclerosis, and regulates glucose metabolism, and is decreased in obese, insulin resistant, and type 2 diabetic patients. Adiponectin circulates in plasma as high, medium, and low molecular weight forms (HMW, MMW......, and LMW). The HMW form was suggested to be closely associated with insulin sensitivity. This study investigated whether diet-induced changes in insulin sensitivity were associated with changes in adiponectin multimeric complexes. SUBJECTS: Twenty obese women with highest and twenty obese women with...... kcal/d less than energy requirements). Plasma HMW, MMW, and LMW forms of adiponectin were quantified using Western blot method. RESULTS: LCD induced comparable weight reduction in responders and non-responders by 8.2 and 7.6 kg. Homeostasis model assessment insulin resistance index decreased by 48...

  14. Metoprolol compared to carvedilol deteriorates insulin-stimulated endothelial function in patients with type 2 diabetes - a randomized study

    DEFF Research Database (Denmark)

    Kveiborg, Britt; Hermann, Thomas S; Major-Pedersen, Atheline; Christiansen, Buris; Rask-Madsen, Christian; Raunsø, Jakob; Køber, Lars; Torp-Pedersen, Christian; Dominguez, Helena

    2010-01-01

    AIM: Studies of beta blockade in patients with type 2 diabetes have shown inferiority of metoprolol treatment compared to carvedilol on indices of insulin resistance. The aim of this study was to examine the effect of metoprolol versus carvedilol on endothelial function and insulin......-stimulated endothelial function in patients with type 2 diabetes. METHOD: 24 patients with type 2 diabetes were randomized to receive either 200 mg metoprolol succinate or 50 mg carvedilol daily. Endothelium-dependent vasodilation was assessed by using venous occlusion plethysmography with increasing doses of intra......-arterial infusions of the agonist serotonin. Insulin-stimulated endothelial function was assessed after co-infusion of insulin for sixty minutes. Vaso-reactivity studies were done before and after the two-month treatment period. RESULTS: Insulin-stimulated endothelial function was deteriorated after treatment with...

  15. Class IIa histone deacetylases affect neuronal remodeling and functional outcome after stroke.

    Science.gov (United States)

    Kassis, Haifa; Shehadah, Amjad; Li, Chao; Zhang, Yi; Cui, Yisheng; Roberts, Cynthia; Sadry, Neema; Liu, Xianshuang; Chopp, Michael; Zhang, Zheng Gang

    2016-06-01

    We have previously demonstrated that stroke induces nuclear shuttling of class IIa histone deacetylase 4 (HDAC4). Stroke-induced nuclear shuttling of HDAC4 is positively and significantly correlated with improved indices of neuronal remodeling in the peri-infarct cortex. In this study, using a rat model for middle cerebral artery occlusion (MCAO), we tested the effects of selective inhibition of class IIa HDACs on functional recovery and neuronal remodeling when administered 24hr after stroke. Adult male Wistar rats (n = 15-17/group) were subjected to 2 h MCAO and orally gavaged with MC1568 (a selective class IIa HDAC inhibitor), SAHA (a non-selective HDAC inhibitor), or vehicle-control for 7 days starting 24 h after MCAO. A battery of behavioral tests was performed. Lesion volume measurement and immunohistochemistry were performed 28 days after MCAO. We found that stroke increased total HDAC activity in the ipsilateral hemisphere compared to the contralateral hemisphere. Stroke-increased HDAC activity was significantly decreased by the administration of SAHA as well as by MC1568. However, SAHA significantly improved functional outcome compared to vehicle control, whereas selective class IIa inhibition with MC1568 increased mortality and lesion volume and did not improve functional outcome. In addition, MC1568 decreased microtubule associated protein 2 (MAP2, dendrites), phosphorylated neurofilament heavy chain (pNFH, axons) and myelin basic protein (MBP, myelination) immunoreactivity in the peri-infarct cortex. Quantitative RT-PCR of cortical neurons isolated by laser capture microdissection revealed that MC1568, but not SAHA, downregulated CREB and c-fos expression. Additionally, MC1568 decreased the expression of phosphorylated CREB (active) in neurons. Taken together, these findings demonstrate that selective inhibition of class IIa HDACs impairs neuronal remodeling and neurological outcome. Inactivation of CREB and c-fos by MC1568 likely contributes to

  16. Vinpocetine suppresses pathological vascular remodeling by inhibiting vascular smooth muscle cell proliferation and migration.

    Science.gov (United States)

    Cai, Yujun; Knight, Walter E; Guo, Shujie; Li, Jian-Dong; Knight, Peter A; Yan, Chen

    2012-11-01

    Abnormal vascular smooth muscle cell (SMC) activation is associated with various vascular disorders such as atherosclerosis, in-stent restenosis, vein graft disease, and transplantation-associated vasculopathy. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. However, its role in pathological vascular remodeling remains unexplored. Herein, we show that systemic administration of vinpocetine significantly reduced neointimal formation in carotid arteries after ligation injury. Vinpocetine also markedly decreased spontaneous remodeling of human saphenous vein explants in ex vivo culture. In cultured SMCs, vinpocetine dose-dependently suppressed cell proliferation and caused G1-phase cell cycle arrest, which is associated with a decrease in cyclin D1 and an increase in p27Kip1 levels. In addition, vinpocetine dose-dependently inhibited platelet-derived growth factor (PDGF)-stimulated SMC migration as determined by the two-dimensional migration assays and three-dimensional aortic medial explant invasive assay. Moreover, vinpocetine significantly reduced PDGF-induced type I collagen and fibronectin expression. It is noteworthy that PDGF-stimulated phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), but not protein kinase B, was specifically inhibited by vinpocetine. Vinpocetine powerfully attenuated intracellular reactive oxidative species (ROS) production, which largely mediates the inhibitory effects of vinpocetine on ERK1/2 activation and SMC growth. Taken together, our results reveal a novel function of vinpocetine in attenuating neointimal hyperplasia and pathological vascular remodeling, at least partially through suppressing ROS production and ERK1/2 activation in SMCs. Given the safety profile of vinpocetine, this study provides insight into the therapeutic potential of vinpocetine in proliferative vascular disorders. PMID:22915768

  17. Effects of Perindopril on Left Ventricular Remodeling and Osteopontin Expression in Rats With Myocardial Infarction

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    To observe the effects of perindopril on left ventricular remodeling and myocardial osteopontin expression in rats with myocardial infarction. Methods In this study male adult SD rats were randomly divided into 3groups: sham-operation group, MI-saline group and MI-perindopril group. Left anterior descending artery was ligated to generate myocardial infarction. Perindopril (2 mg/kg body weight/day) was administered from the next day of MI.Four weeks later, left ventricular diameter (LVEDD and LVESD) and left ventricular ejection fraction was estimated with echocardiography, LVSP, LVEDP and ± dp/dtmax was detected with hemodynamic measurement, cardiomyocyte diameter and interstitial fibrosis infiltration were evaluated with histological methods, and myocardium osteopontin protein expression level was detected with western blot. Results ①Compared with the sham-operation group, all rats with MI developed significant systolic and diastolic dysfunction, as was indicated by decreased LVEF, LVSP and ± dp/dtmax, as well as increased LVEDP. ②Rats with MI showed significantly dilated left ventricles and higher ventricular weight / body weight ratio, significantly increased cardiomyocyte diameter and marked interstitial fibrosis in the non-infarction area. ③Perindopril treatment partly prevented cardiac dysfunction and left ventricular remodeling as indicated by the parameters mentioned above. ④No osteopontin protein was detected in myocardium of sham-operation rats. In rats with MI, high level osteopontin protein expression was significantly inhibited by perindopril treatment. Conclusions In rats with MI, perindopril treatment significantly prevented left ventricular remodeling and myocardium osteopontin protein expression.

  18. Metabolomic heterogeneity of pulmonary arterial hypertension.

    Directory of Open Access Journals (Sweden)

    Yidan Zhao

    Full Text Available Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH, the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH.

  19. Insulin resistance, insulin sensitization and inflammation in polycystic ovarian syndrome

    Directory of Open Access Journals (Sweden)

    Dhindsa G

    2004-04-01

    Full Text Available It is estimated that 5-10% of women of reproductive age have polycystic ovarian syndrome (PCOS. While insulin resistance is not part of the diagnostic criteria for PCOS, its importance in the pathogenesis of PCOS cannot be denied. PCOS is associated with insulin resistance independent of total or fat-free body mass. Post-receptor defects in the action of insulin have been described in PCOS which are similar to those found in obesity and type 2 diabetes. Treatment with insulin sensitizers, metformin and thiazolidinediones, improve both metabolic and hormonal patterns and also improve ovulation in PCOS. Recent studies have shown that PCOS women have higher circulating levels of inflammatory mediators like C-reactive protein, tumour necrosis factor- , tissue plasminogen activator and plasminogen activator inhibitor-1 (PAI-1 . It is possible that the beneficial effect of insulin sensitizers in PCOS may be partly due to a decrease in inflammation.

  20. In vivo characterization of insulin uptake by dog renal cortical epithelium

    International Nuclear Information System (INIS)

    In vivo 125I-labeled insulin uptake by dog renal tubular epithelium was studied using the single-pass multiple indicator dilution (MID) method and analyzed by a computer-assisted model of transcapillary exchange and substrate-cell interaction. Anesthetized dogs received an intrarenal arterial bolus of multiple tracers: [3H]dextran greater than 70 kDa (plasma reference), [14C]inulin (extracellular reference), and 125I-insulin. Rapid serial sampling of the renal venous and urine outflows was performed. The renal venous outflow curves of 125I-insulin fell below [14C]inulin implying postglomerular extraction and antiluminal membrane (ALM) uptake. The fractional urine recovery of 125I-insulin was less than 0.03, indicating luminal tubular uptake of filtered hormone. After intravenous infusion of unlabeled insulin, repeat MID runs with tracer revealed saturable ALM uptake as evidenced by the 125I-insulin renal venous outflow curves approaching [14C]inulin. Luminal tubular uptake was unchanged and therefore unsaturable. The 125I-insulin renal venous data were studied using three mathematical models, incorporating postglomerular reversible binding, irreversible binding or transport. The best fit was obtained using the transport model. The modeling analysis is consistent with either uptake into a virtual epithelial membrane space (i.e., insulin never enters the cell but binds to or is distributed along the ALM) or insulin actually enters the intracellular compartment. In vivo uptake of 125I-insulin ALM is characterized by a Km of 15.44 nM

  1. Multiscale Bone Remodelling with Spatial P Systems

    CERN Document Server

    Cacciagrano, Diletta; Merelli, Emanuela; Tesei, Luca; 10.4204/EPTCS.40.6

    2010-01-01

    Many biological phenomena are inherently multiscale, i.e. they are characterized by interactions involving different spatial and temporal scales simultaneously. Though several approaches have been proposed to provide "multilayer" models, only Complex Automata, derived from Cellular Automata, naturally embed spatial information and realize multiscaling with well-established inter-scale integration schemas. Spatial P systems, a variant of P systems in which a more geometric concept of space has been added, have several characteristics in common with Cellular Automata. We propose such a formalism as a basis to rephrase the Complex Automata multiscaling approach and, in this perspective, provide a 2-scale Spatial P system describing bone remodelling. The proposed model not only results to be highly faithful and expressive in a multiscale scenario, but also highlights the need of a deep and formal expressiveness study involving Complex Automata, Spatial P systems and other promising multiscale approaches, such as ...

  2. Matrix Remodeling in Pulmonary Fibrosis and Emphysema.

    Science.gov (United States)

    Kulkarni, Tejaswini; O'Reilly, Philip; Antony, Veena B; Gaggar, Amit; Thannickal, Victor J

    2016-06-01

    Pulmonary fibrosis and emphysema are chronic lung diseases characterized by a progressive decline in lung function, resulting in significant morbidity and mortality. A hallmark of these diseases is recurrent or persistent alveolar epithelial injury, typically caused by common environmental exposures such as cigarette smoke. We propose that critical determinants of the outcome of the injury-repair processes that result in fibrosis versus emphysema are mesenchymal cell fate and associated extracellular matrix dynamics. In this review, we explore the concept that regulation of mesenchymal cells under the influence of soluble factors, in particular transforming growth factor-β1, and the extracellular matrix determine the divergent tissue remodeling responses seen in pulmonary fibrosis and emphysema. PMID:26741177

  3. Renovascular hypertension causes cerebral vascular remodeling

    Institute of Scientific and Technical Information of China (English)

    Yamei Tang; Xiangpen Li; Yi Li; Qingyu Shen; Xiaoming Rong; Ruxun Huang; Ying Peng

    2011-01-01

    Renovascular hypertensive rats (RHRs) were developed using the 2-kidney, 2-clip method. All RHRs at 10 weeks displayed high permeability of the cerebral surface blood vessels. Vascular casts of the RHRs showed that the vascular network was sparse. The arterioles of the RHRs at 10 weeks had smaller lumen diameters, but thicker vessel walls with hyalinosis formation compared with control animals. The endothelial cell membrane appeared damaged, and microthrombus formed. After ischemia, the infarction size was larger in RHRs than in control animals. These results suggest that cerebral arterioles in RHRs underwent structural remodeling. High blood pressure may aggravate the severity of brain injury in cerebral ischemia and affect the recovery of ischemia.

  4. Arterial pulse wave velocity, inflammatory markers, pathological GH and IGF states, cardiovascular and cerebrovascular disease

    Directory of Open Access Journals (Sweden)

    Michael R Graham

    2008-12-01

    Full Text Available Michael R Graham1, Peter Evans2, Bruce Davies1, Julien S Baker11Health and Exercise Science Research Unit, Faculty of Health Sport and Science, University of Glamorgan, Pontypridd, Wales, United Kingdom; 2Royal Gwent Hospital, Newport, Gwent, United KingdomAbstract: Blood pressure (BP measurements provide information regarding risk factors associated with cardiovascular disease, but only in a specific artery. Arterial stiffness (AS can be determined by measurement of arterial pulse wave velocity (APWV. Separate from any role as a surrogate marker, AS is an important determinant of pulse pressure, left ventricular function and coronary artery perfusion pressure. Proximal elastic arteries and peripheral muscular arteries respond differently to aging and to medication. Endogenous human growth hormone (hGH, secreted by the anterior pituitary, peaks during early adulthood, declining at 14% per decade. Levels of insulin-like growth factor-I (IGF-I are at their peak during late adolescence and decline throughout adulthood, mirror imaging GH. Arterial endothelial dysfunction, an accepted cause of increased APWV in GH deficiency (GHD is reversed by recombinant human (rh GH therapy, favorably influencing the risk for atherogenesis. APWV is a noninvasive method for measuring atherosclerotic and hypertensive vascular changes increases with age and atherosclerosis leading to increased systolic blood pressure and increased left ventricular hypertrophy. Aerobic exercise training increases arterial compliance and reduces systolic blood pressure. Whole body arterial compliance is lowered in strength-trained individuals. Homocysteine and C-reactive protein are two infl ammatory markers directly linked with arterial endothelial dysfunction. Reviews of GH in the somatopause have not been favorable and side effects of treatment have marred its use except in classical GHD. Is it possible that we should be assessing the combined effects of therapy with rhGH and rh

  5. PNPLA3 mediates hepatocyte triacylglycerol remodeling.

    Science.gov (United States)

    Ruhanen, Hanna; Perttilä, Julia; Hölttä-Vuori, Maarit; Zhou, You; Yki-Järvinen, Hannele; Ikonen, Elina; Käkelä, Reijo; Olkkonen, Vesa M

    2014-04-01

    The I148M substitution in patatin-like phospholipase domain containing 3 (PNPLA3(I148M)) determines a genetic form of nonalcoholic fatty liver disease. To elucidate the mode of PNPLA3 action in human hepatocytes, we studied effects of WT PNPLA3 (PNPLA3(WT)) and PNPLA3(I148M) on HuH7 cell lipidome after [(13)C]glycerol labeling, cellular turnover of oleic acid labeled with 17 deuterium atoms ([D17]oleic acid) in triacylglycerols (TAGs), and subcellular distribution of the protein variants. PNPLA3(I148M) induced a net accumulation of unlabeled TAGs, but not newly synthesized total [(13)C]TAGs. Principal component analysis (PCA) revealed that both PNPLA3(WT) and PNPLA3(I148M) induced a relative enrichment of TAGs with saturated FAs or MUFAs, with concurrent enrichment of polyunsaturated phosphatidylcholines. PNPLA3(WT) associated in PCA with newly synthesized [(13)C]TAGs, particularly 52:1 and 50:1, while PNPLA3(I148M) associated with similar preexisting TAGs. PNPLA3(WT) overexpression resulted in increased [D17]oleic acid labeling of TAGs during 24 h, and after longer incubations their turnover was accelerated, effects not detected with PNPLA3(I148M). PNPLA3(I148M) localized more extensively to lipid droplets (LDs) than PNPLA3(WT), suggesting that the substitution alters distribution of PNPLA3 between LDs and endoplasmic reticulum/cytosol. This study reveals a function of PNPLA3 in FA-selective TAG remodeling, resulting in increased TAG saturation. A defect in TAG remodeling activity likely contributes to the TAG accumulation observed in cells expressing PNPLA3(I148M). PMID:24511104

  6. [Medication of the month. Insulin glargine (Lantus)].

    Science.gov (United States)

    Scheen, A J

    2004-02-01

    Insulin glargine (Lantus) is a human insulin analogue produced by recombinant DNA technology and recently launched by Aventis. Modification of the human insulin molecule at position A21 and at the C-terminus of the B-chain results in the formation of a stable compound that is soluble at pH 4.0, but forms amorphous microprecipitates in subcutaneous tissue (pH > 7,4) from which small amounts of insulin glargine are gradually released. The plasma concentration versus time profile of insulin glargine is therefore relatively constant over 24 hours as compared to conventional human insulins, especially NPH. This allows once-daily injection as basal insulin therapy, at any moment of the clock time (but if possible at the same time from day to day). Reproducibility of plasma insulin levels is also improved with insulin glargine as compared to human NPH insulin. Insulin glargine administration should be combined to rapid insulin injections, before each meal in order to control postprandial hyperglycaemia, or with oral antidiabetic agents in type 2 diabetes. The pharmacokinetic properties of insulin glargine allow an easier titration of basal insulin dose, which should facilitate adequate blood glucose control while decreasing the risk of hypoglycaemia, especially during night time. Insulin glargine use is safe with no increased antigenicity, immunogenicity or mitogenicity reactions as compared to human insulin. Optimal use of this new insulin analogue should be integrated in a global management of the diabetic patient as well as in a new culture of insulin therapy. PMID:15112902

  7. Co-associations between insulin sensitivity and measures of liver function, subclinical inflammation, and hematology.

    Science.gov (United States)

    Godsland, Ian F; Johnston, Desmond G

    2008-09-01

    Clustering of risk factors for coronary heart disease and diabetes is well established, particularly in relation to insulin resistance. To determine whether evaluation of risk factor clustering will contribute to risk assessment, it is first necessary to discriminate co-association between risk factors from correlation. We undertook this in a large homogenous group, using a sophisticated measure of insulin sensitivity and a broad range of risk factors. Cross-sectional analysis of an occupational cohort using regression and factor analyses was performed. Subjects were 472 apparently healthy white men. The main outcome measures were insulin sensitivity, S(I), by minimal model analysis of the intravenous glucose tolerance test plus liver function and hematologic variables, including the inflammation indices, leukocyte count, and erythrocyte sedimentation rate. The S(I) correlated independently with serum gamma-glutamyl transferase (GGT), aspartate transaminase, and alkaline phosphatase activities; blood pressure; leukocyte count; and erythrocyte sedimentation rate (P GGT activity (loadings >0.40). Mean arterial pressure was not a feature (loading 0.29), neither were indices of subclinical inflammation. In apparently healthy men, blood pressure and indices of subclinical inflammation do not cluster with other insulin resistance-related risk factors, despite correlating with insulin sensitivity. In contrast, both GGT activity and uric acid concentrations correlated with insulin sensitivity and co-associated with insulin resistance-related risk factors and are therefore components of a true risk factor cluster. PMID:18702943

  8. ALK7 Gene Polymorphism is Associated with Metabolic Syndrome Risk and Cardiovascular Remodeling

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wenchao; Wang, Hui; Zhang, Wei [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Lv, Ruijuan [Department of Emergency, Qilu Hospital of Shandong University, Jinan (China); Wang, Zhihao [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Department of Geriatrics, Qilu Hospital of Shandong University, Jinan (China); Shang, Yuanyuan; Zhang, Yun; Zhong, Ming [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Chen, Yuguo; Tang, Mengxiong, E-mail: tangmengxiongsdu8@163.com [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Department of Emergency, Qilu Hospital of Shandong University, Jinan (China)

    2013-08-15

    Activin receptor-like kinase 7 (ALK7) is a type I receptor for the TGF-β superfamily and has recently been demonstrated to play an important role in the maintenance of metabolic homeostasis. To investigate the association of the ALK7 gene polymorphism with metabolic syndrome (MetS) and cardiovascular remodeling in MetS patients. The single nucleotide polymorphism rs13010956 in the ALK7 gene was genotyped in 351 Chinese subjects undergoing carotid and cardiac ultrasonography. The associations of the ALK7 gene polymorphism with the MetS phenotype, MetS parameters, and cardiovascular ultrasonic features were analyzed. The rs13010956 polymorphism in the ALK7 gene was found to be significantly associated with the MetS phenotype in females (p < 0.05) and was also significantly associated with blood pressure in the total (p < 0.05) and female populations (p < 0.01). Further analysis revealed that rs13010956 was associated with mean intima-media thickness of the carotid arteries in females (p < 0.05). After control for body mass index, blood pressure, fasting blood glucose, and triglycerides, rs13010956 was also found to be significantly associated with left ventricular mass index in the total (p < 0.05) and female populations (p < 0.05). Our findings suggested that the ALK7 gene polymorphism rs13010956 was significantly associated with MetS risk in females and may be involved in cardiovascular remodeling in MetS patients.

  9. Effects of losartan on ventricular remodeling in experimental infarction in rats

    Directory of Open Access Journals (Sweden)

    Zornoff Leonardo A. M.

    2000-01-01

    Full Text Available OBJECTIVE: To evaluate the effects of losartan on ventricular remodeling and on survival after myocardial infarction in rats. METHODS: After surgical occlusion of left coronary artery, 84 surviving male Wistar rats were divided into two groups: LO treated with losartan (20mg/kg/day, n=33 and NT (n=51, without medication. After 3 months, we analyzed mortality; ventricular to body mass ratio (VM /BM; myocardial hydroxyproline concentration (HOP; isovolumetric pressure, +dp/dt, -dp/dt, and diastolic volume/left ventricle mass ratio (VO/LV. RESULTS: Mortality was: LO = 22%, and NT = 47% (p0.05. The V0/LV values (median were 0.24 mL/g in group LO and 0.31 mL/g in group NT (p<0.05 compared to NT group. There were no differences between the groups for +dp/dt and -dp/dt parameters. CONCLUSION: 1- The use of losartan myocardial infarction causes an attenuation of ventricular remodeling, bringing about an increased survival, an attenuation of ventricular hypertrophy and dilation, and an improvement of the isovolumetric pressure; 2- the treatment does not modify the myocardial collagen concentration.

  10. Effect of Wenxin Granule on Ventricular Remodeling and Myocardial Apoptosis in Rats with Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Aiming Wu

    2013-01-01

    Full Text Available Aim. To determine the effect of a Chinese herbal compound named Wenxin Granule on ventricular remodeling and myocardial apoptosis in rats with myocardial infarction (MI. Methods. Male Sprague-Dawley (SD rats were randomly divided into four groups: the control group, the model group, the metoprolol group, and the Wenxin Granule group (WXKL group with sample size (n of 7 rats in each group. An MI model was established in all rats by occlusion of the left anterior descending coronary artery (the control group was without occlusion. Wenxin Granule (1.35 g/kg/day, metoprolol (12 mg/kg/day, and distilled water (5 mL/kg/day for the control and model groups were administered orally for 4 weeks. Ultrasonic echocardiography was used to examine cardiac structural and functional parameters. Myocardial histopathological changes were observed using haematoxylin and eosin (H&E dyeing. Myocardial apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL staining. Serum angiotensin II (Ang II concentration was measured using the enzyme-linked immunosorbent assay (ELISA. Results. It was found that Wenxin Granule could partially reverse ventricular remodeling, improve heart function, alleviate the histopathological damage, inhibit myocardial apoptosis, and reduce Ang II concentration in rats with MI. Conclusions. The results of the current study suggest that Wenxin Granule may be a potential alternative and complementary medicine for the treatment of MI.

  11. Ranolazine reduces remodeling of the right ventricle and provoked arrhythmias in rats with pulmonary hypertension.

    Science.gov (United States)

    Liles, John T; Hoyer, Kirsten; Oliver, Jason; Chi, Liguo; Dhalla, Arvinder K; Belardinelli, Luiz

    2015-06-01

    Pulmonary arterial hypertension (PAH) is a progressive disease that often results in right ventricular (RV) failure and death. During disease progression, structural and electrical remodeling of the right ventricle impairs pump function, creates proarrhythmic substrates, and triggers for arrhythmias. Notably, RV failure and lethal arrhythmias are major contributors to cardiac death in patients with PAH that are not directly addressed by currently available therapies. Ranolazine (RAN) is an antianginal, anti-ischemic drug that has cardioprotective effects in experimental and clinical settings of left-sided heart dysfunction. RAN also has antiarrhythmic effects due to inhibition of the late sodium current in cardiomyocytes. We therefore hypothesized that RAN could reduce the maladaptive structural and electrical remodeling of the right ventricle and could prevent triggered ventricular arrhythmias in the monocrotaline rat model of PAH. Indeed, in both in vivo and ex vivo experimental settings, chronic RAN treatment reduced electrical heterogeneity (right ventricular-left ventricular action potential duration dispersion), shortened heart-rate corrected QT intervals in the right ventricle, and normalized RV dysfunction. Chronic RAN treatment also dose-dependently reduced ventricular hypertrophy, reduced circulating levels of B-type natriuretic peptide, and decreased the expression of fibrotic markers. In addition, the acute administration of RAN prevented isoproterenol-induced ventricular tachycardia/ventricular fibrillation and subsequent cardiovascular death in rats with established PAH. These results support the notion that RAN can improve the electrical and functional properties of the right ventricle, highlighting its potential benefits in the setting of RV impairment. PMID:25770134

  12. Effect of carvedilol on cardiac function and left ventricular remodeling in rats after acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    张军; 贾国良; 王海昌

    2003-01-01

    Objective: To observe the effect of carvedilol injection on left ventricular function and collagen remodeling in rat with myocardial infarction. Methods: Sixty rats with a model of myocardial infarction were randomly divided into nine groups. The rats of therapeutical group were treated with carvedilol injection (2 mg/d intraperitoneal injection) and/or captopil (2 g/L drinking water). Acute myocardial infarction (AMI) group did not receive drug treatment. The animals were sacrificed at 4 weeks and 8 weeks after coronary artery ligation. The levels of plasma angiotensin Ⅱ and plasma aldosterone and left ventricle function were determined at different time. The collagen content and the ratio of type I and Ⅲ collagen of noninfarcted area were also assessed. Results: Compared with AMI group, the levels of plasma and myocardium angiotensin Ⅱ and plasma aldosterone in both carvedilol and captopil group decreased at the eighth week (P<0.05). In addition, carvedilol improved systolic and diastolic function (P<0.05). Compared with sham group, both collagen content and the ratio of type Ⅰ/Ⅲ collagen of noninfarcted area increased in AMI4 and AMI8 group (P<0.05). The hydroxyproline levels and the ratio of type Ⅰ/Ⅲ collagen significantly decreased after carvedilol and/or captopil treatment , compared with AMI group at 4 or 8 week (P<0.05). Conclusion: Carvedilol can improve cardiac function after myocardial infarction and has beneficial effect on left ventricular remodeling.

  13. ALK7 Gene Polymorphism is Associated with Metabolic Syndrome Risk and Cardiovascular Remodeling

    International Nuclear Information System (INIS)

    Activin receptor-like kinase 7 (ALK7) is a type I receptor for the TGF-β superfamily and has recently been demonstrated to play an important role in the maintenance of metabolic homeostasis. To investigate the association of the ALK7 gene polymorphism with metabolic syndrome (MetS) and cardiovascular remodeling in MetS patients. The single nucleotide polymorphism rs13010956 in the ALK7 gene was genotyped in 351 Chinese subjects undergoing carotid and cardiac ultrasonography. The associations of the ALK7 gene polymorphism with the MetS phenotype, MetS parameters, and cardiovascular ultrasonic features were analyzed. The rs13010956 polymorphism in the ALK7 gene was found to be significantly associated with the MetS phenotype in females (p < 0.05) and was also significantly associated with blood pressure in the total (p < 0.05) and female populations (p < 0.01). Further analysis revealed that rs13010956 was associated with mean intima-media thickness of the carotid arteries in females (p < 0.05). After control for body mass index, blood pressure, fasting blood glucose, and triglycerides, rs13010956 was also found to be significantly associated with left ventricular mass index in the total (p < 0.05) and female populations (p < 0.05). Our findings suggested that the ALK7 gene polymorphism rs13010956 was significantly associated with MetS risk in females and may be involved in cardiovascular remodeling in MetS patients

  14. Carotid body, insulin and metabolic diseases: unravelling the links

    Directory of Open Access Journals (Sweden)

    Silvia V Conde

    2014-10-01

    Full Text Available The carotid bodies (CB are peripheral chemoreceptors that sense changes in arterial blood O2, CO2 and pH levels. Hypoxia, hypercapnia and acidosis activate the CB, which respond by increasing the action potential frequency in their sensory nerve, the carotid sinus nerve (CSN. CSN activity is integrated in the brain stem to induce a panoply of cardiorespiratory reflexes aimed, primarily, to normalize the altered blood gases, via hyperventilation, and to regulate blood pressure and cardiac performance, via sympathetic nervous system (SNS activation. Besides its role in the cardiorespiratory control the CB has been proposed as a metabolic sensor implicated in the control of energy homeostasis and, more recently, in the regulation of whole body insulin sensitivity. Hypercaloric diets cause CB overactivation in rats, which seems to be at the origin of the development of insulin resistance and hypertension, core features of metabolic syndrome and type 2 diabetes. Consistent with this notion, CB sensory denervation prevents metabolic and hemodynamic alterations in hypercaloric feed animal. Obstructive sleep apnoea (OSA is another chronic disorder characterized by increased CB activity and intimately related with several metabolic and cardiovascular abnormalities. In this manuscript we review in a concise manner the putative pathways linking CB chemoreceptors deregulation with the pathogenesis of insulin resistance and arterial hypertension. Also, the link between chronic intermittent hypoxia (CIH and insulin resistance is discussed. Then, a final section is devoted to debate strategies to reduce CB activity and its use for prevention and therapeutics of metabolic diseases with an emphasis on new exciting research in the modulation of bioelectronic signals, likely to be central in the future.

  15. Cardiovascular function, compliance, and connective tissue remodeling in the turtle, Trachemys scripta, following thermal acclimation.

    Science.gov (United States)

    Keen, Adam N; Shiels, Holly A; Crossley, Dane A

    2016-07-01

    Low temperature directly alters cardiovascular physiology in freshwater turtles, causing bradycardia, arterial hypotension, and a reduction in systemic blood pressure. At the same time, blood viscosity and systemic resistance increase, as does sensitivity to cardiac preload (e.g., via the Frank-Starling response). However, the long-term effects of these seasonal responses on the cardiovascular system are unclear. We acclimated red-eared slider turtles to a control temperature (25°C) or to chronic cold (5°C). To differentiate the direct effects of temperature from a cold-induced remodeling response, all measurements were conducted at the control temperature (25°C). In anesthetized turtles, cold acclimation reduced systemic resistance by 1.8-fold and increased systemic blood flow by 1.4-fold, resulting in a 2.3-fold higher right to left (R-L; net systemic) cardiac shunt flow and a 1.8-fold greater shunt fraction. Following a volume load by bolus injection of saline (calculated to increase stroke volume by 5-fold, ∼2.2% of total blood volume), systemic resistance was reduced while pulmonary blood flow and systemic pressure increased. An increased systemic blood flow meant the R-L cardiac shunt was further pronounced. In the isolated ventricle, passive stiffness was increased following cold acclimation with 4.2-fold greater collagen deposition in the myocardium. Histological sections of the major outflow arteries revealed a 1.4-fold higher elastin content in cold-acclimated animals. These results suggest that cold acclimation alters cardiac shunting patterns with an increased R-L shunt flow, achieved through reducing systemic resistance and increasing systemic blood flow. Furthermore, our data suggests that cold-induced cardiac remodeling may reduce the stress of high cardiac preload by increasing compliance of the vasculature and decreasing compliance of the ventricle. Together, these responses could compensate for reduced systolic function at low temperatures in

  16. VASCULAR REMODELING IN HYPERTENSION: ANGIOGENESIS FEATURES

    Directory of Open Access Journals (Sweden)

    L. A. Haisheva

    2014-07-01

    Full Text Available Aim — cross-sectional study of changes in various segments of the vascular bed in arterial hypertension (AH, defining the role of inducers and inhibitors of angiogenesis in these processes.Materials and methods. The study included 99 patients with arterial hypertension of I–II degree, average age of 63.2 ± 2.6 years, diseaseduration 9.2 ± 7.2 years.Results. It was found that patients with arterial hypertension have disorders in all segments of vascular bed: endothelial dysfunction (highvWF, microcirculatory disorders, and increased pulse wave velocity (PWV of elastic-type vessels. The level of angioginesis factors doesnot depend on such parameters as gender, age, body mass index. Smoking and duration of hypertension influence on vascular endothelialgrowth factor raise and endostatin levels are higher in patients with family history of cardiovascular diseases. Duration of disease is directlycorrelated with microcirculatory disorders and the PWV, correlation between microcirculatory disorders and pulse wave velocity indicatetheir common processes.

  17. Role of insulin hormone in modulation of inflammatory phenomena

    Directory of Open Access Journals (Sweden)

    Antonio Di Petta

    2011-09-01

    Full Text Available Evidence demonstrates the involvement of hormones in thedevelopment of inflammatory response. Inflammation evokes markedstructural alterations of microvasculature, besides migration ofleukocytes from microcirculation to the site of lesion. These alterations are caused primarily by release or activation of endogenous mediators, in which hormones play an integral role in this regulatory system. Binding sites for many hormones may be characterized by vascular structures and hematogenous cells involved with the inflammatory response. Quantitative alterations of inflammatory events involving the decrease in microvascular response to inflammatory mediators, deficiency in the leukocyte-endothelium interaction, reduction of cell concentration in the inflammatory exudate, and failure of the phagocyte function of mononuclear cells were observed in insulindeficient states. Therefore, inflammation is not merely a local response, but rather a process controlled by hormones in which insulin plays an essential role in modulation of these phenomena, and assures tissue repair and remodeling within the limits of normality.

  18. Effect of Cocaine on Pulmonary Vascular Remodeling and Hemodynamics in Human Immunodeficiency Virus-Transgenic Rats.

    Science.gov (United States)

    Dalvi, Pranjali; Spikes, Leslie; Allen, Julie; Gupta, Vijayalaxmi G; Sharma, Himanshu; Gillcrist, Marion; Montes de Oca, Jamison; O'Brien-Ladner, Amy; Dhillon, Navneet K

    2016-08-01

    Human immunodeficiency virus (HIV)-related pulmonary arterial hypertension has been found to be more prevalent in intravenous drug users. Our earlier cell-culture findings reported down-regulation of bone morphogenetic protein receptors (BMPRs) in combination with enhanced proliferation of human pulmonary arterial smooth muscle cells (PASMCs) in the presence of HIV-Trans-activator of transcription (Tat) and cocaine compared with either treatment alone. Here, we report physiologic evidence of significant increases in mean pulmonary arterial pressure in HIV-transgenic (Tg) rats intraperitoneally administered 40 mg/kg body weight cocaine (HIV-cocaine group) once daily for 21 days when compared with HIV-Tg rats given saline (HIV group) or wild-type (WT) Fischer 334 rats treated with (WT-cocaine group) and without cocaine (WT group). In addition, right ventricle systolic pressure was also found to be significantly higher in the HIV-cocaine rats compared with the WT group. Significant down-regulation in protein expression of BMPR-2 and BMPR-1B was observed in total lung extract from HIV-cocaine rats compared with the other three groups. Furthermore, the PASMCs isolated from HIV-cocaine rats demonstrated a higher level of proliferation and lower levels of apoptosis compared with cells isolated from other rat groups. Interestingly, corroborating our earlier cell-culture findings, we observed higher expression of BMPR-2 and BMPR-1B messenger RNA and significantly lower levels of BMPR-2 and BMPR-1B protein in HIV-cocaine PASMCs compared with cells isolated from all other groups. In conclusion, our findings support an additive effect of cocaine and HIV on smooth muscle dysfunction, resulting in enhanced pulmonary vascular remodeling with associated elevation of mean pulmonary arterial pressure and right ventricle systolic pressure in HIV-Tg rats exposed to cocaine. PMID:26820592

  19. Additional disulfide bonds in insulin

    DEFF Research Database (Denmark)

    Vinther, Tine N; Pettersson, Ingrid; Huus, Kasper;

    2015-01-01

    -chain is flexible and can adapt multiple conformations. We examined how well disulfide bond predictions algorithms could identify disulfide bonds in this region of insulin. In order to identify stable insulin analogues with additional disulfide bonds, which could be expressed, the Cβ cut-off distance had...... higher yields in comparison to analogues with additional disulfide bonds that were more difficult to predict. In contrast, addition of the fourth disulfide bond rendered all analogues resistant to fibrillation under stress conditions and all stable analogues bound to the insulin receptor with picomolar...... predicts four additional four disulfide insulin analogues which could be expressed. Although the location of the additional disulfide bonds is only slightly shifted, this shift impacts both stability and activity of the resulting insulin analogues....

  20. The chromatin remodeler SPLAYED regulates specific stress signaling pathways.

    Directory of Open Access Journals (Sweden)

    Justin W Walley

    2008-12-01

    Full Text Available Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD is required for the expression of selected genes downstream of the jasmonate (JA and ethylene (ET signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks.

  1. Cardiovascular effects of basal insulins

    Directory of Open Access Journals (Sweden)

    Mannucci E

    2015-07-01

    Full Text Available Edoardo Mannucci,1 Stefano Giannini,2 Ilaria Dicembrini1 1Diabetes Agency, Careggi Teaching Hospital, Florence, 2Section of Endocrinology, Department of Biomedical Clinical and Experimental Sciences, University of Florence and Careggi University Hospital, Florence, Italy Abstract: Basal insulin is an important component of treatment for both type 1 and type 2 diabetes. One of the principal aims of treatment in patients with diabetes is the prevention of diabetic complications, including cardiovascular disease. There is some evidence, although controversial, that attainment of good glycemic control reduces long-term cardiovascular risk in both type 1 and type 2 diabetes. The aim of this review is to provide an overview of the potential cardiovascular safety of the different available preparations of basal insulin. Current basal insulin (neutral protamine Hagedorn [NPH], or isophane and basal insulin analogs (glargine, detemir, and the more recent degludec differ essentially by various measures of pharmacokinetic and pharmacodynamic effects in the bloodstream, presence and persistence of peak action, and within-subject variability in the glucose-lowering response. The currently available data show that basal insulin analogs have a lower risk of hypoglycemia than NPH human insulin, in both type 1 and type 2 diabetes, then excluding additional harmful effects on the cardiovascular system mediated by activation of the adrenergic system. Given that no biological rationale for a possible difference in cardiovascular effect of basal insulins has been proposed so far, available meta-analyses of publicly disclosed randomized controlled trials do not show any signal of increased risk of major cardiovascular events between the different basal insulin analogs. However, the number of available cardiovascular events in these trials is very small, preventing any clear-cut conclusion. The results of an ongoing clinical trial comparing glargine and degludec with

  2. Studies on insulin receptor, 2

    International Nuclear Information System (INIS)

    The present study is to investigate an influence of starvation and high fat diet on insulin receptor of the plasma membrane by means of radioreceptor assay using 125I-labelled insulin. Male guinea pigs of Hartley strain were employed for the starvation study, and 125I-insulin binding capacity on the plasma membrane of the liver and kidney was determined at 24, 48 and 72 hours of the fast after the last meal. Male rats of Wistar strain were employed for the high fat study where the diet containing 35% of butter was fed ad libitum for 38 or 68 days. The animals were killed at the fast of 12 hours, and 125I-insulin binding capacity on the plasma membrane of the liver was determined. The results obtained are summarized as follows: 1) An increase in 125I-insulin binding capacity on the plasma membrane of the liver and kidney was observed by the starvation for 24 to 72 hours. 2) The mechanism of the increase by starvation was considered to be different by the organs; it was due to an increase in number of insulin receptor in the liver, and due to an increase in affinity of insulin receptor in the kidney. 3) In non-obese rats fed with high fat diet, the number of insulin receptor on the liver plasma membrane showed a decrease, and this observation clearly indicated that the decrease in number of the receptor did not depend on the obesity. 4) Obese rats also fed with high fat diet presented a decrease in number of insulin receptor without an elevation of insulin levels in the circulating blood. This indicated that at least in the obese rats fed with high fat diet, the decrease in number of the receptor was not due to hyperinsulinemia. (author)

  3. INSULIN RESISTANCE AND CAROTID ATHEROSCLEROSIS IN 221 PATIENTS WITH POTENTIAL HYPERGLYCEMIA

    Institute of Scientific and Technical Information of China (English)

    Bo Yang; Tian-de Li; Jin-song Wang; Guang Zhi; Wen-sheng Jin; Yong Xu

    2005-01-01

    Objective To investigate the relationship between insulin resistance and carotid atherosclerosis in patients with potential hyperglycemia.Methods A total of 221 patients were recruited among those with potential hyperglycemia. All participants underwent physical examination, medical history interview, and 75 g oral glucose tolerance test. Venous blood was sampled for measurement of insulin and cholesterol levels. The intima-media thickness (IMT) in bilateral common carotid arteries was observed by B-mode ultrasound. Insulin resistance index was calculated by homeostasis model assessment (HOMA-IR).Subjects were stratified in quintiles according to HOMA-IR values. Risk factors and atherosclerotic parameters were analyzed.Results With HOMA-IR value increase, incidence of impaired glucose tolerance, diabetes mellitus, hypertension, and coronary artery disease increased, the levels of triglyceride (TG), low density lipoprotein cholesterol (LDL-C), fasting plasma glucose, 2 hour plasma glucose, and fasting insulin increased as well, while the level of high density lipoprotein cholesterol (HDL-C) decreased. Meanwhile, all atherosclerotic parameters increased. Multivariate regression analysis showed that TG, total cholesterol, HDL-C, LDL-C levels, and In(HOMA-IR) were related to IMT, hence were risk factors for IMT increase.Conchsion Insulin resistance is implicated in atherogenesis.

  4. Remodeling of endogenous mammary epithelium by breast cancer stem cells.

    Science.gov (United States)

    Parashurama, Natesh; Lobo, Neethan A; Ito, Ken; Mosley, Adriane R; Habte, Frezghi G; Zabala, Maider; Smith, Bryan R; Lam, Jessica; Weissman, Irving L; Clarke, Michael F; Gambhir, Sanjiv S

    2012-10-01

    Poorly regulated tissue remodeling results in increased breast cancer risk, yet how breast cancer stem cells (CSC) participate in remodeling is unknown. We performed in vivo imaging of changes in fluorescent, endogenous duct architecture as a metric for remodeling. First, we quantitatively imaged physiologic remodeling of primary branches of the developing and regenerating mammary tree. To assess CSC-specific remodeling events, we isolated CSC from MMTV-Wnt1 (mouse mammary tumor virus long-term repeat enhancer driving Wnt1 oncogene) breast tumors, a well studied model in which tissue remodeling affects tumorigenesis. We confirm that CSC drive tumorigenesis, suggesting a link between CSC and remodeling. We find that normal, regenerating, and developing gland maintain a specific branching pattern. In contrast, transplantation of CSC results in changes in the branching patterns of endogenous ducts while non-CSC do not. Specifically, in the presence of CSC, we identified an increased number of branches, branch points, ducts which have greater than 40 branches (5/33 for CSC and 0/39 for non-CSC), and histological evidence of increased branching. Moreover, we demonstrate that only CSC implants invade into surrounding stroma with structures similar to developing mammary ducts (nine for CSC and one for non-CSC). Overall, we demonstrate a novel approach for imaging physiologic and pathological remodeling. Furthermore, we identify unique, CSC-specific, remodeling events. Our data suggest that CSC interact with the microenvironment differently than non-CSC, and that this could eventually be a therapeutic approach for targeting CSC. PMID:22899386

  5. Celiac Artery Compression Syndrome

    Directory of Open Access Journals (Sweden)

    Mohammed Muqeetadnan

    2013-01-01

    Full Text Available Celiac artery compression syndrome is a rare disorder characterized by episodic abdominal pain and weight loss. It is the result of external compression of celiac artery by the median arcuate ligament. We present a case of celiac artery compression syndrome in a 57-year-old male with severe postprandial abdominal pain and 30-pound weight loss. The patient eventually responded well to surgical division of the median arcuate ligament by laparoscopy.

  6. Popliteal artery entrapment syndrome.

    LENUS (Irish Health Repository)

    O'Leary, D P

    2010-01-01

    Popliteal artery entrapment syndrome is a rare abnormality of the anatomical relationship between the popliteal artery and adjacent muscles or fibrous bands in the popliteal fossa. The following is a case report of a 19 year old female, in whom popliteal artery entrapment syndrome was diagnosed, and successfully treated surgically. A review of literature is also presented and provides details on how PAES is classified, diagnosed both clinically and radiologically, and treated surgically.

  7. Coeliac artery compression syndrome

    OpenAIRE

    OKTAY, Özgür; MEMİŞ, Ahmet; Parildar, Mustafa; Oran, İsmail

    2003-01-01

    Celiac artery compression syndrome, also called median arcuate ligament compression syndrome, causes gastrointestinal ischemia secondary to compression of the proximal portion of the celiac artery just beyond its origin by the median arcuate ligament of the diaphragm. This syndrome is frequently demonstrated on aortography performed in patients without complaints of intestinal angina. Isolated stenosis or even occlusion of the celiac artery is always compensated for by collateral circul...

  8. Human relaxin gene expression delivered by bioreducible dendrimer polymer for post-infarct cardiac remodeling in rats.

    Science.gov (United States)

    Lee, Young Sook; Choi, Joung-Woo; Oh, Jung-Eun; Yun, Chae-Ok; Kim, Sung Wan

    2016-08-01

    In consensus, myocardial infarction (MI) is defined as irreversible cell death secondary to prolonged ischemia in heart. The aim of our study was to evaluate the therapeutic potential of anti-fibrotic human Relaxin-expressing plasmid DNA with hypoxia response element (HRE) 12 copies (HR1) delivered by a dendrimer type PAM-ABP polymer G0 (HR1/G0) after MI on functional, hemodynamic, geometric, and cardiac extracellular matrix (ECM) remodeling in rats. HR1/G0 demonstrated significantly improved LV systolic function, hemodynamic parameters, and geometry on 1 wk and 4 wks after MI in rats, compared with I/R group. The resolution of regional wall motional abnormalities and the increased blood flow of infarct-related coronary artery supported functional improvements of HR1/G0. Furthermore, HR1/G0 polyplex showed favorable post-infarct cardiac ECM remodeling reflected on the favorable cardiac ECM compositions. Overall, this is the first study, which presented an advanced platform for the gene therapy that reverses adverse cardiac remodeling after MI with a HR1 gene delivered by a bioreducible dendrimer polymer in the cardiac ECM. PMID:27174688

  9. Osteoblast recruitment routes in human cancellous bone remodeling

    DEFF Research Database (Denmark)

    Kristensen, Helene B; Levin Andersen, Thomas; Marcussen, Niels;

    2014-01-01

    It is commonly proposed that bone forming osteoblasts recruited during bone remodeling originate from bone marrow perivascular cells, bone remodeling compartment canopy cells, or bone lining cells. However, an assessment of osteoblast recruitment during adult human cancellous bone remodeling is...... lacking. We addressed this question by quantifying cell densities, cell proliferation, osteoblast differentiation markers, and capillaries in human iliac crest biopsy specimens. We found that recruitment occurs on both reversal and bone-forming surfaces, as shown by the cell density and osterix levels on...

  10. Coronary artery bypass surgery in the diabetic patient.

    LENUS (Irish Health Repository)

    Maher, M

    2012-02-03

    Coronary artery and peripheral occlusive arterial disease frequently complicate diabetes mellitus, with death due to atherosclerotic coronary artery disease being three times more likely in diabetic compared to non-diabetic patients. The profile of 32 diabetic patients and 32 matched controls who underwent coronary artery bypass (CABG) is studied and their early and late postoperative outcomes are described. The mean age was 61 +\\/- 1 year in both groups. The diabetic group comprised 26 non-insulin dependent and 6 insulin dependent diabetics, who had a mean duration of diabetes of 8.5 years (range 2 months--35 years). The median number of grafts per patient performed in the diabetic group and the control group was 3.5 and 3 respectively. There was no mortality in the series, however considerably greater wound morbidity rates were encountered in the diabetic group when compared to matched controls. One renal transplant patient in the diabetic group suffered irreversible acute tubular necrosis and became dialysis dependent post-operatively. Longterm follow-up showed no longterm mortality in either group, with full relief of angina achieved in 75% of diabetic patients compared with 87.5% of matched controls. In addition diabetic patients suffered greater longterm cardiac morbidity than the control group (21.8% versus 12.5%). The results of this study suggest that CABG is a safe operation for the diabetic patient. Diabetic patients receive satisfactory symptomatic relief of angina, but suffer increased perioperative wound complications and greater incidence of longterm cardiac morbidity.

  11. The Role of Insulin, Insulin Growth Factor, and Insulin-Degrading Enzyme in Brain Aging and Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Claude Messier

    2005-01-01

    Full Text Available Most brain insulin comes from the pancreas and is taken up by the brain by what appears to be a receptor-based carrier. Type 2 diabetes animal models associated with insulin resistance show reduced insulin brain uptake and content. Recent data point to changes in the insulin receptor cascade in obesity-related insulin resistance, suggesting that brain insulin receptors also become less sensitive to insulin, which could reduce synaptic plasticity. Insulin transport to the brain is reduced in aging and in some animal models of type 2 diabetes; brain insulin resistance may be present as well. Studies examining the effect of the hyperinsulinic clamp or intranasal insulin on cognitive function have found a small but consistent improvement in memory and changes in brain neuroelectric parameters in evoked brain potentials consistent with improved attention or memory processing. These effects appear to be due to raised brain insulin levels. Peripheral levels of Insulin Growth Factor-I (IGF-I are associated with glucose regulation and influence glucose disposal. There is some indication that reduced sensitivity to insulin or IGF-I in the brain, as observed in aging, obesity, and diabetes, decreases the clearance of Aβ amyloid. Such a decrease involves the insulin receptor cascade and can also increase amyloid toxicity. Insulin and IGF-I may modulate brain levels of insulin degrading enzyme, which would also lead to an accumulation of Aβ amyloid.

  12. Imaging the vertebral artery

    Energy Technology Data Exchange (ETDEWEB)

    Tay, Keng Yeow; U-King-Im, Jean Marie; Trivedi, Rikin A.; Higgins, Nicholas J.; Cross, Justin J.; Antoun, Nagui M. [Addenbrooke' s Hospital and University of Cambridge, Department of Radiology, Cambridge (United Kingdom); Davies, John R.; Weissberg, Peter L. [Addenbrooke' s Hospital and University of Cambridge, Division of Cardiovascular Medicine, Cambridge (United Kingdom); Gillard, Jonathan H. [Addenbrooke' s Hospital and University of Cambridge, Department of Radiology, Cambridge (United Kingdom); Addenbrooke' s Hospitald, University Department of Radiology, Cambridge (United Kingdom)

    2005-07-01

    Although conventional intraarterial digital subtraction angiography remains the gold standard method for imaging the vertebral artery, noninvasive modalities such as ultrasound, multislice computed tomographic angiography and magnetic resonance angiography are constantly improving and are playing an increasingly important role in diagnosing vertebral artery pathology in clinical practice. This paper reviews the current state of vertebral artery imaging from an evidence-based perspective. Normal anatomy, normal variants and a number of pathological entities such as vertebral atherosclerosis, arterial dissection, arteriovenous fistula, subclavian steal syndrome and vertebrobasilar dolichoectasia are discussed. (orig.)

  13. Peripheral artery disease - legs

    Science.gov (United States)

    ... if they have a history of: Abnormal cholesterol Diabetes Heart disease (coronary artery disease) High blood pressure ( hypertension ) Kidney disease involving hemodialysis Smoking Stroke ( cerebrovascular disease )

  14. Effects of Buyang Huanwu Decoction on Ventricular Remodeling and Differential Protein Profile in a Rat Model of Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Ying Chun Zhou

    2012-01-01

    Full Text Available Buyang Huanwu decoction (BYHWD is a well-known and canonical Chinese medicine formula from “Correction on Errors in Medical Classics” in Qing dynasty. Here, we show that BYHWD could alleviate the ventricular remodeling induced by left anterior descending (LAD artery ligation in rats. BYHWD treatment (18 g/kg/day decreased heart weight/body weight (HW/BW, left ventricle (LV dimension at end diastole (LVDd and increased LV ejection fraction (LVEF and LV fractional shortening (LVFS significantly compared to model group at the end of 12 weeks. The collagen volume of BYHWD group was more significantly decreased than that of model group. Proteomic analysis showed that atrial natriuretic factor (ANF was downregulated; heat shock protein beta-6 (HSPB6 and peroxiredoxin-6 (PRDX6 were upregulated in BYHWD-treated group among successfully identified proteins. The apoptotic index (AI was reduced by BYHWD accompanied by decreased expression of Bax and caspase 3 activity, increased Bcl-2/Bax ratio, and phosphorylation of HSPB6 compared to that of model group. Taken together, these results suggest that BYHWD can alleviate ventricular remodeling induced by LAD artery ligation. The antiremodeling effects of BYHWD are conferred by decreasing AI through affecting multiple targets including increased Bcl-2/Bax ratio and decreased caspase 3 activity that might be via upregulated PRDX6, phosphorylation of HSPB6 and subsequently reduction of ANF.

  15. Effects of buyang huanwu decoction on ventricular remodeling and differential protein profile in a rat model of myocardial infarction.

    Science.gov (United States)

    Zhou, Ying Chun; Liu, Bin; Li, Ying Jia; Jing, Lin Lin; Wen, Ge; Tang, Jing; Xu, Xin; Lv, Zhi Ping; Sun, Xue Gang

    2012-01-01

    Buyang Huanwu decoction (BYHWD) is a well-known and canonical Chinese medicine formula from "Correction on Errors in Medical Classics" in Qing dynasty. Here, we show that BYHWD could alleviate the ventricular remodeling induced by left anterior descending (LAD) artery ligation in rats. BYHWD treatment (18 g/kg/day) decreased heart weight/body weight (HW/BW), left ventricle (LV) dimension at end diastole (LVDd) and increased LV ejection fraction (LVEF) and LV fractional shortening (LVFS) significantly compared to model group at the end of 12 weeks. The collagen volume of BYHWD group was more significantly decreased than that of model group. Proteomic analysis showed that atrial natriuretic factor (ANF) was downregulated; heat shock protein beta-6 (HSPB6) and peroxiredoxin-6 (PRDX6) were upregulated in BYHWD-treated group among successfully identified proteins. The apoptotic index (AI) was reduced by BYHWD accompanied by decreased expression of Bax and caspase 3 activity, increased Bcl-2/Bax ratio, and phosphorylation of HSPB6 compared to that of model group. Taken together, these results suggest that BYHWD can alleviate ventricular remodeling induced by LAD artery ligation. The antiremodeling effects of BYHWD are conferred by decreasing AI through affecting multiple targets including increased Bcl-2/Bax ratio and decreased caspase 3 activity that might be via upregulated PRDX6, phosphorylation of HSPB6 and subsequently reduction of ANF. PMID:23049607

  16. Impaired glutathione redox system paradoxically suppresses angiotensin II-induced vascular remodeling.

    Directory of Open Access Journals (Sweden)

    Kazuma Izawa

    Full Text Available BACKGROUND: Angiotensin II (AII plays a central role in vascular remodeling via oxidative stress. However, the interaction between AII and reduced glutathione (GSH redox status in cardiovascular remodeling remains unknown. METHODS: In vivo: The cuff-induced vascular injury model was applied to Sprague Dawley rats. Then we administered saline or a GSH inhibitor, buthionine sulfoximine (BSO, 30 mmol/L in drinking water for a week, subsequently administered 4 more weeks by osmotic pump with saline or AII (200 ng/kg/minute to the rats. In vitro: Incorporation of bromodeoxyuridine (BrdU was measured to determine DNA synthesis in cultured rat vascular smooth muscle cells (VSMCs. RESULTS: BSO reduced whole blood GSH levels. Systolic blood pressure was increased up to 215 ± 4 mmHg by AII at 4 weeks (p<0.01, which was not affected by BSO. Superoxide production in vascular wall was increased by AII and BSO alone, and was markedly enhanced by AII+BSO. The left ventricular weight to body weight ratio was significantly increased in AII and AII+BSO as compared to controls (2.52 ± 0.08, 2.50 ± 0.09 and 2.10 ± 0.07 mg/g respectively, p<0.05. Surprisingly, the co-treatment of BSO totally abolished these morphological changes. Although the vascular circumferential wall stress was well compensated in AII, significantly increased in AII+BSO. The anti-single-stranded DNA staining revealed increasing apoptotic cells in the neointima of injured arteries in BSO groups. BrdU incorporation in cultured VSMCs with AII was increased dose-dependently. Furthermore it was totally abolished by BSO and was reversed by GSH monoethyl ester. CONCLUSIONS: We demonstrated that a vast oxidative stress in impaired GSH redox system totally abolished AII-induced vascular, not cardiac remodeling via enhancement of apoptosis in the neointima and suppression of cell growth in the media. The drastic suppression of remodeling may result in fragile vasculature intolerable to mechanical

  17. Prevalence of breast arterial calcification in hypertensive patients

    Energy Technology Data Exchange (ETDEWEB)

    Cetin, M. E-mail: muzuncetin@yahoo.comakdeniz9999@ttent.net.tr; Cetin, R.; Tamer, N

    2004-01-01

    AIM: To determine the age-specific prevalence of breast arterial calcifications in patients with systemic hypertension. METHODS: The mammograms and patient records of 2406 women who underwent screening or diagnostic mammography were reviewed retrospectively. Mammograms were evaluated for the presence of arterial calcification and results were coded. Hypertension was defined as use of anti-hypertensive agents and diabetes was defined as use of oral hypoglycaemic agents or insulin. RESULTS: The prevalence of breast arterial calcification among hypertensives (17.6%) was lower than among diabetics (25.4%). The prevalence in the non-diabetic, non-hypertensive group was lowest (7.3%). The prevalence increased with age in all three groups. The highest prevalence was found in diabetics older than 60 years (81.8%). Breast arterial calcification was not found among women younger than 40 years. CONCLUSION: Breast arterial calcification is associated with hypertension and prevalence increases with age. Breast arterial calcification on mammograms may indicate unsuspected hypertension especially in non-diabetic patients.

  18. Prevalence of breast arterial calcification in hypertensive patients

    International Nuclear Information System (INIS)

    AIM: To determine the age-specific prevalence of breast arterial calcifications in patients with systemic hypertension. METHODS: The mammograms and patient records of 2406 women who underwent screening or diagnostic mammography were reviewed retrospectively. Mammograms were evaluated for the presence of arterial calcification and results were coded. Hypertension was defined as use of anti-hypertensive agents and diabetes was defined as use of oral hypoglycaemic agents or insulin. RESULTS: The prevalence of breast arterial calcification among hypertensives (17.6%) was lower than among diabetics (25.4%). The prevalence in the non-diabetic, non-hypertensive group was lowest (7.3%). The prevalence increased with age in all three groups. The highest prevalence was found in diabetics older than 60 years (81.8%). Breast arterial calcification was not found among women younger than 40 years. CONCLUSION: Breast arterial calcification is associated with hypertension and prevalence increases with age. Breast arterial calcification on mammograms may indicate unsuspected hypertension especially in non-diabetic patients

  19. Calcium antagonists, diltiazem and nifedipine, protect broilers against low temperature-induced pulmonary hypertension and pulmonary vascular remodeling.

    Science.gov (United States)

    Yang, Ying; Gao, Mingyu; Guo, Yuming; Qiao, Jian

    2010-08-01

    This study was designed to determine whether calcium antagonists, diltiazem and nifedipine, can depress low temperature-induced pulmonary hypertension (PH) in broilers (also known as ascites) and to characterize their efficacy on hemodynamics and pulmonary artery function. Chicks were randomly allocated into six experimental groups and orally administered with vehicle, 5.0 mg/kg body weight (BW)/12 h nifedipine or 15.0 mg/kg BW/12 h diltiazem from 16 to 43 days of age under low temperature. The mean pulmonary arterial pressure (mPAP), the ascites heart index (AHI), the erythrocyte packed cell volume (PCV) and the relative percentage of medial pulmonary artery thickness were examined on days 29, 36 and 43. The data showed that administration of diltiazem protected broilers from low temperature-induced pulmonary hypertension and vascular remodeling. Although nifedipine prevented mPAP from increasing during the early stage, it did not suppress the development of PH during the late stage and did not keep heart rate (HR), PCV, AHI and the thickness of pulmonary small artery smooth muscle layer at the normal levels. Taken together, our results showed that diltiazem can effectively prevent low temperature-induced pulmonary hypertension in broilers with fewer side-effects and may be a potential compound for the prevention of this disease in poultry industry. PMID:20662820

  20. 21 CFR 522.1160 - Insulin.

    Science.gov (United States)

    2010-04-01

    ...) of insulin. (2) Each mL of protamine zinc recombinant human insulin suspension contains 40 IU of... control has been attained. (B) Protamine zinc recombinant human insulin. Administer an initial dose of 0.1... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Insulin. 522.1160 Section 522.1160 Food and...

  1. Influence of insulin antibodies on pharmacokinetics and bioavailability of recombinant human and highly purified beef insulins in insulin dependent diabetics.

    OpenAIRE

    Gray, R S; Cowan, P.; Di Mario, U.; Elton, R A; Clarke, B F; Duncan, L J

    1985-01-01

    Sixteen insulin dependent diabetics of long standing, with undetectable fasting plasma C peptide concentrations, and eight non-diabetic controls were each infused intravenously with biosynthetic human and highly purified beef insulin (1 mU/kg/min) while euglycaemia was maintained by a Biostator. No difference was observed between the two insulins in respect of insulin pharmacokinetics or biological action. The diabetics showed appreciable insulin resistance, manifested by a 40% reduction in t...

  2. Variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects

    International Nuclear Information System (INIS)

    The aim of this study was to assess regional and global variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects and to evaluate potentially responsible factors. Twenty men with a mean age of 64 years, no history of cardiovascular disease, and normal blood pressure, bicycle exercise test, electrocardiogram and echocardiography were studied [P(coronary artery disease) <5%]. Whole-body insulin sensitivity and insulin-stimulated myocardial glucose uptake were measured during hyperinsulinaemic euglycaemic glucose clamp with fluorine-18 fluorodeoxyglucose, and myocardial rest and hyperaemic blood flow during dipyridamole infusion were measured with nitrogen-13 ammonia and positron emission tomography in 16 left ventricular myocardial segments. Intra-individual and inter-individual variability of insulin-stimulated myocardial glucose uptake [relative dispersion = (standard deviation/mean)] was 13% and 29% respectively. Although inter-individual variability of glucose uptake and blood flow at rest was of the same magnitude, no correlation was found between these measures. Regional and global insulin-stimulated myocardial glucose uptake correlated linearly with whole-body insulin sensitivity (r=0.51, P<0.05 and r=0.56, P<0.01). The strongest independent association by multivariate linear regression analysis was found between myocardial glucose uptake and hyperaemic blood flow (r=0.63, P<0.005). We conclude that in healthy elderly subjects, insulin-stimulated myocardial glucose uptake is homogeneous throughout the left ventricle, but has moderate inter-individual variability. Inter-individual variability of insulin-stimulated myocardial glucose uptake is primarily explained by variability in coronary vascular reactivity and tissue insulin sensitivity. (orig.)

  3. Alternative routes of insulin delivery

    Institute of Scientific and Technical Information of China (English)

    Ranjith K. Krishnankutty; Aju Mathew; Saikiran K. Sedimbi; Shrikumar Suryanarayan; Carani B. Sanjeevi

    2009-01-01

    Parenteral route of insulin administration has been the mode of treatment for all Type 1 diabetics and Type 2 diabetics with complications. Patient compliance has really been a major concern for this route of administration. Several alternative routes of administration are under consideration for effective glycemic control, including oral, inhaled, buccal, nasal, and patch routes. One of the approaches involving inhaled insulin has now reached the market. Several other candidates may reach the market in the near future, the promising one being oral insulin.

  4. Cutaneous allergy to human (recombinant DNA) insulin.

    Science.gov (United States)

    Grammer, L C; Metzger, B E; Patterson, R

    1984-03-16

    p6 report two cases of cutaneous allergy to human (recombinant DNA) insulin. Each patient had a history of systemic allergic reactions to porcine insulin and was at least as reactive to human as to porcine insulin by end-point cutaneous titration. Both patients' insulin allergy was managed with animal insulins and both have done well. Our experience with these two patients indicates that human insulin (rDNA) should not be expected to be efficacious in all patients with systemic allergy to insulin. PMID:6366262

  5. Mammary remodelling and metabolic activity in dairy goats

    DEFF Research Database (Denmark)

    Safayi, Sina

    ) differences between PP and MP animals with respect to milk production and lactation persistency may be related to differences in mammary growth and remodelling also during lactation, 2) the factors responsible for interfering with mammary remodelling in continuous lactation throughout the dry period into the...... present thesis aimed to address the hypotheses that 1) differences between PP and MP animals with respect to milk production and lactation persistency may be related to differences in mammary growth and remodelling also during lactation, 2) the factors responsible for interfering with mammary remodelling...... be effectively renewed as one lactation comes to an end and prior to onset of the next lactation. Generally, the level of milk production and the changes in milk yield over the course of lactation depend on three main factors: 1) the number of MEC, which in turn is affected by the balance between the...

  6. New ways of insulin delivery.

    Science.gov (United States)

    Heinemann, L

    2010-02-01

    When Exubera (EXU), the first inhaled insulin formulation to make it through the clinical development process, was introduced to the market some years ago it was hoped that this would be the first in a series of novel insulin formulations applied by this route. In addition, it was hoped that inhaled insulin would pave the way for other alternative routes of insulin administration (ARIA), i.e. oral insulin, nasal insulin or transdermal insulin to mention only some of the different attempts that have been studied in the last 90 years. The failure of EXU, i.e. its withdrawal from the market due to insufficient market success, was followed by the cessation of nearly all other attempts to develop inhaled insulin formulations. Currently there is only one company (MannKind) which moves sturdily ahead with their Technosphere insulin. This company has submitted an NDA for their product recently and hopes to bring it to the market by the end of 2010 or early 2011. Even if the product is able to pass the approval hurdles in the USA and Europe, this does not guarantee that it will become a market success. Many diabetologists were sceptical about the need/advantages of inhaled insulin/EXU from the start and the introduction of this product has raised even more scepticism. Reports about 'side effects' (development of lung cancer in patients treated with EXU) of inhaled insulin are also not helpful, even if the causality of the appearance of cancer with this type of insulin therapy is not proven. One of the very negative consequences of stopping EXU are the huge financial losses to Pfizer. The managers in charge in other pharmaceutical companies and also most venture capitalists are reluctant to invest in ARIA nowadays. This in turn means that many of the small companies that try to develop new forms of insulin administration have issues when they try to find a big brother and/or sufficient financial support. Clearly the economic crisis has further aggravated this issue. One can

  7. Deep trophoblast invasion and spiral artery remodelling in the placental bed of the lowland gorilla

    DEFF Research Database (Denmark)

    Pijnenborg, R; Vercruysse, L; Carter, Anthony Michael

    2011-01-01

    chimpanzee, we postulated the occurrence of deep invasion in gorilla pregnancy. Tissues were processed for histology (PAS, orcein), lectin staining (Ulex europaeus agglutinin 1) and immunohistochemistry (cytokeratin 7/17, α-actin). A specimen of young but undetermined gestational age included deep placental...

  8. Deep trophoblast invasion and spiral artery remodelling in the placental bed of the chimpanzee

    DEFF Research Database (Denmark)

    Pijnenborg, R; Vercruysse, L; Carter, Anthony Michael

    2011-01-01

    -actin, as well as Ulex europaeus agglutinin 1 (UEA1) lectin staining, in this archival material. In both specimens interstitial trophoblast invasion had occurred in both decidua and myometrium. Because of a lack of published data on fetal growth for this species, fetal sizes (7cm and 13cm) could not be...

  9. Cutaneous remodeling and photorejuvenation using radiofrequency devices

    Directory of Open Access Journals (Sweden)

    Elsaie Mohamed

    2009-01-01

    Full Text Available Radio frequency (RF is electromagnetic radiation in the frequency range of 3-300GHz. The primary effects of RF energy on living tissue are considered to be thermal. The goal of the new devices based on these frequency ranges is to heat specific layers of the skin. The directed use of RF can induce dermal heating and cause collagen degeneration. Wound healing mechanisms promote the remodeling of collagen and wound contraction, which ultimately clinically enhances the appearance of mild to moderate skin laxity. Preliminary studies have reported efficacy in the treatment of laxity that involves the periorbital area and jowls. Because RF energy is not dependent on specific chromophore interaction, epidermal melanin is not at risk of destruction and treatment of all skin types is possible. As such, radiofrequency-based systems have been used successfully for nonablative skin rejuvenation, atrophic scar revision and treatment of unwanted hair, vascular lesions and inflammatory acne. The use of RF is becoming more popular, although a misunderstanding exists regarding the mechanisms and limitations of its actions. This concise review serves as an introduction and guide to many aspects of RF in the non ablative rejuvenation of skin.

  10. Remodeling of alveolar septa after murine pneumonectomy.

    Science.gov (United States)

    Ysasi, Alexandra B; Wagner, Willi L; Bennett, Robert D; Ackermann, Maximilian; Valenzuela, Cristian D; Belle, Janeil; Tsuda, Akira; Konerding, Moritz A; Mentzer, Steven J

    2015-06-15

    In most mammals, removing one lung (pneumonectomy) results in the compensatory growth of the remaining lung. In mice, stereological observations have demonstrated an increase in the number of mature alveoli; however, anatomic evidence of the early phases of alveolar growth has remained elusive. To identify changes in the lung microstructure associated with neoalveolarization, we used tissue histology, electron microscopy, and synchrotron imaging to examine the configuration of the alveolar duct after murine pneumonectomy. Systematic histological examination of the cardiac lobe demonstrated no change in the relative frequency of dihedral angle components (Ends, Bends, and Junctions) (P > 0.05), but a significant decrease in the length of a subset of septal ends ("E"). Septal retraction, observed in 20-30% of the alveolar ducts, was maximal on day 3 after pneumonectomy (P alveolar duct diameter ratio (Dout:Din) was significantly lower 3 days after pneumonectomy compared to all controls except for the detergent-treated lung (P surface tension within the alveolar duct, resulting in a new equilibrium at a higher total energy and lower surface area. The spatial and temporal association of these microstructural changes with postpneumonectomy lung growth suggests that these changes represent an early phase of alveolar duct remodeling. PMID:26078396

  11. The effect of rowing on endothelial function and insulin action in healthy controls and in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Olsen, D B; Scheede-Bergdahl, C; Reving, D;

    2011-01-01

    with T2DM (n=9) and matched controls (n=8). Before and after training (30 min every other day), all subjects underwent sequential graded brachial artery infusions of non-insulin vasodilators (acetylcholine; sodium nitroprusside; adenosine). Forearm blood flow was improved by training in controls...

  12. Redox Regulation of Insulin Degradation by Insulin-Degrading Enzyme

    OpenAIRE

    Cordes, Crystal M.; Bennett, Robert G.; Siford, Gerri L.; Hamel, Frederick G.

    2011-01-01

    Insulin-degrading enzyme (IDE) is a thiol sensitive peptidase that degrades insulin and amyloid β, and has been linked to type 2 diabetes mellitus and Alzheimer's disease. We examined the thiol sensitivity of IDE using S-nitrosoglutathione, reduced glutathione, and oxidized glutathione to distinguish the effects of nitric oxide from that of the redox state. The in vitro activity of IDE was studied using either partially purified cytosolic enzyme from male Sprague-Dawley rats, or purified rat ...

  13. Inhaled insulin: overview of a novel route of insulin administration

    OpenAIRE

    Lucy D Mastrandrea

    2010-01-01

    Lucy D MastrandreaDepartment of Pediatrics, School of Medicine and Biochemical Sciences, University at Buffalo, Buffalo, NY, USAAbstract: Diabetes is a chronic disease characterized by inadequate insulin secretion with resulting hyperglycemia. Diabetes complications include both microvascular and macrovascular disease, both of which are affected by optimal diabetes control. Many individuals with diabetes rely on subcutaneous insulin administration by injection or continuous infusion to contro...

  14. Medical therapies for pulmonary arterial hypertension.

    Science.gov (United States)

    Pulido, Tomas; Zayas, Nayeli; de Mendieta, Maitane Alonso; Plascencia, Karen; Escobar, Jennifer

    2016-05-01

    Pulmonary Arterial hypertension (PAH) is a chronic and progressive disease characterized by an increase in pulmonary vascular resistance due to severe remodeling of the small pulmonary arteries. In PAH, the endothelial cells fail to maintain their homeostatic balance, with the consequent impaired production of vasodilators and over-expression of vasoconstrictors and proliferators. Current treatment of PAH is based on the discovery of three main pathways of endothelial dysfunction (prostacyclin, nitric oxide and endothelin-1), and includes drugs such as prostacyclin analogs, phosphodiesterase-5 inhibitors and endothelin receptor antagonists (ERAs). Recently approved drugs that act through these classic pathways include riociguat (cyclic GMP stimulator) and macitentan (a tissue specific dual ERA). However, several new drugs and new pathways are under study. New targeted therapies include tyrosine kinase inhibitors, Rho kinase inhibitors and serotonin receptor blockers. There are now ten drugs approved for the treatment of PAH that, alone or in combination, have changed the natural history of this disease. The new drugs will allow us to further modified the patients' life expectancy and move towards a cure. PMID:26791159

  15. Remodeling of the bone material containing microcracks: A theoretical analysis

    Science.gov (United States)

    Ramtani, S.; Zidi, M.

    1999-12-01

    The question is, what happens when the bone loses its ability for load-driven adaptation, when damage is no longer repaired as it seems to be the case for bone loss associated with age, medication or disease? In this study, we tempt to show how damage can influence the remodeling process. A thermodynamic theoretical framework is therefore provided as a basis for a consistent formulation of bone remodeling involving a chemical reaction and mass transfer between two constituents in presence of microcracks.

  16. Collagen scaffold remodeling by human mesenchymal stem cells

    OpenAIRE

    Han, SJ; Chan, BP

    2011-01-01

    Type I collagen has been widely used as scaffold for tissue engineering because of its excellent biocompatibility and negligible immunogenicity. We previously have developed a collagen microencapsulation technology entrapping many cells including human mesenchymal stem cells (hMSCs) in microspheres made of nanofibrous collagen meshwork. Nevertheless, little is understood about how stem cells interact with and remodel the collagen meshwork. This study aims to investigate collagen remodeling by...

  17. The relationship between eosinophilia and airway remodelling in mild asthma

    OpenAIRE

    Wilson, S J; Rigden, H.M.; Ward, J. A.; Laviolette, M.; Jarjour, N N; Djukanović, R.

    2013-01-01

    Background Eosinophilia is a marker of corticosteroid responsiveness and risk of exacerbation in asthma; although it has been linked to submucosal matrix deposition, its relationship with other features of airway remodelling is less clear. Objective The aim of this study was to investigate the relationship between airway eosinophilia and airway remodelling. Methods Bronchial biopsies from subjects (n = 20 in each group) with mild steroid-naïve asthma, with either low (0–0....

  18. Bilateral popliteal arterial dissection.

    Science.gov (United States)

    Chen, Po-Liang; Ko, Shih-Yu; Tan, Ken-Hing

    2012-01-01

    A clinical feature of bilateral popliteal arterial dissection without involving the descending aorta, bilateral iliac, as well as femoral arteries has never been reported in the past literature. We report a 56-year-old man with hypertension and coronary artery disease who presented to our emergency department with complaints of bilateral knee pain after long-distance walking. Physical examination was notable for elevated blood pressure, but there was no palpable pulsation over dorsalis pedis arteries on his feet. Laboratory evaluation revealed a d-dimer level of 35.2 mg/L (FEU) on the day of the test and 1.2 mg/L one and a half months ago (normal level, <0.55). These findings were suggestive of a recent-onset peripheral arterial occlusive disorder. Computed tomography of the aorta showed bilateral popliteal arterial dissection with arterial intimal flap. Abdominal aorta, bilateral iliac, and femoral arteries remained intact with only arteriosclerotic change. Minimally invasive endovascular stent grafting was then performed. The patient had an uneventful recovery. PMID:21106320

  19. Effect of Intensive Blood Pressure Control on Cardiovascular Remodeling in Hypertensive Patients with Nephrosclerosis

    Directory of Open Access Journals (Sweden)

    Otelio Randall

    2013-01-01

    Full Text Available Pulse pressure (PP, a marker of arterial system properties, has been linked to cardiovascular (CV complications. We examined (a association between unit changes of PP and (i composite CV outcomes and (ii development of left-ventricular hypertrophy (LVH and (b effect of mean arterial pressure (MAP control on rate of change in PP. We studied 1094 nondiabetics with nephrosclerosis in the African American Study of Kidney Disease and Hypertension. Subjects were randomly assigned to usual MAP goal (102–107 mmHg or a lower MAP goal (≤92 mmHg and randomized to beta-blocker, angiotensin converting enzyme inhibitor, or calcium channel blocker. After covariate adjustment, a higher PP was associated with increased risk of CV outcome (RR = 1.28, CI = 1.11–1.47, P<0.01 and new LVH (RR = 1.26, CI = 1.04–1.54, P=0.02. PP increased at a greater rate in the usual than in lower MAP groups (slope ± SE: 1.08 ± 0.15 versus 0.42 ± 0.15 mmHg/year, P=0.002, but not by the antihypertensive treatment assignment. Observations indicate that control to a lower MAP slows the progression of PP, a correlate of cardiovascular remodeling and complications, and may be beneficial to CV health.

  20. Rapamycin attenuates hypoxia-induced pulmonary vascular remodeling and right ventricular hypertrophy in mice

    Directory of Open Access Journals (Sweden)

    Tillmanns Harald H

    2007-02-01

    Full Text Available Abstract Background Chronic hypoxia induces pulmonary arterial hypertension (PAH. Smooth muscle cell (SMC proliferation and hypertrophy are important contributors to the remodeling that occurs in chronic hypoxic pulmonary vasculature. We hypothesized that rapamycin (RAPA, a potent cell cycle inhibitor, prevents pulmonary hypertension in chronic hypoxic mice. Methods Mice were held either at normoxia (N; 21% O2 or at hypobaric hypoxia (H; 0.5 atm; ~10% O2. RAPA-treated animals (3 mg/kg*d, i.p. were compared to animals injected with vehicle alone. Proliferative activity within the pulmonary arteries was quantified by staining for Ki67 (positive nuclei/vessel and media area was quantified by computer-aided planimetry after immune-labeling for α-smooth muscle actin (pixel/vessel. The ratio of right ventricle to left ventricle plus septum (RV/[LV+S] was used to determine right ventricular hypertrophy. Results Proliferative activity increased by 34% at day 4 in mice held under H (median: 0.38 compared to N (median: 0.28, p = 0.028 which was completely blocked by RAPA (median HO+RAPA: 0.23, p = 0.003. H-induced proliferation had leveled off within 3 weeks. At this time point media area had, however, increased by 53% from 91 (N to 139 (H, p Conclusion Therapy with rapamycin may represent a new strategy for the treatment of pulmonary hypertension.

  1. YKL-40 a new biomarker in patients with acute coronary syndrome or stable coronary artery disease

    DEFF Research Database (Denmark)

    Wang, Y.Z.; Ripa, R.S.; Johansen, J.S.; Gabrielsen, A.; Steinbruchel, D.A.; Friis, Jørn Torp; Bindslev, L.; Haack-Sorensen, M.; Jørgensen, Erik; Kastrup, J.

    2008-01-01

    Background. YKL-40 is involved in remodelling and angiogenesis in non-cardiac inflammatory diseases. Aim was to quantitate plasma YKL-40 in patients with ST-elevation myocardial infarction (STEMI) or stable chronic coronary artery disease (CAD), and YKL-40 gene activation in human myocardium....... Methods and results. We included 73 patients: I) 20 patients with STEMI; II) 28 patients with stable CAD; III) 15 CAD patients referred for coronary by-pass surgery. YKL-40 mRNA expression was measured in myocardium subtended by stenotic or occluded arteries and areas with no apparent disease; and IV) 10...

  2. Current european regulatory perspectives on insulin analogues

    OpenAIRE

    Enzmann Harald G; Weise Martina

    2011-01-01

    Abstract Insulin analogues are increasingly considered as an alternative to human insulin in the therapy of diabetes mellitus. Insulin analogues (IAs) are chemically different from human insulin and may have different pharmacokinetic or pharmacodynamic properties. The significance of the modifications of the insulin molecule for the safety profile of IAs must be considered. This review describes the regulatory procedure and the expectations for the scientific content of European marketing aut...

  3. Insulin resistance and Alzheimer’s disease

    OpenAIRE

    de la Monte, Suzanne M.

    2009-01-01

    Emerging data demonstrate pivotal roles for brain insulin resistance and insulin deficiency as mediators of cognitive impairment and neurodegeneration, particularly Alzheimer’s disease (AD). Insulin and insulin-like growth factors (IGFs) regulate neuronal survival, energy metabolism, and plasticity, which are required for learning and memory. Hence, endogenous brain-specific impairments in insulin and IGF signaling account for the majority of AD-associated abnormalities. However, a second maj...

  4. Changes in the structure-function relationship of elastin and its impact on the proximal pulmonary arterial mechanics of hypertensive calves

    OpenAIRE

    Lammers, Steven R.; Kao, Phil H.; Qi, H. Jerry; Hunter, Kendall; Lanning, Craig; Albietz, Joseph; Hofmeister, Stephen; Mecham, Robert; Stenmark, Kurt R.; Shandas, Robin

    2008-01-01

    Extracellular matrix remodeling has been proposed as one mechanism by which proximal pulmonary arteries stiffen during pulmonary arterial hypertension (PAH). Although some attention has been paid to the role of collagen and metallomatrix proteins in affecting vascular stiffness, much less work has been performed on changes in elastin structure-function relationships in PAH. Such work is warranted, given the importance of elastin as the structural protein primarily responsible for the passive ...

  5. Cell Matrix Remodeling Ability Shown by Image Spatial Correlation

    Directory of Open Access Journals (Sweden)

    Chi-Li Chiu

    2013-01-01

    Full Text Available Extracellular matrix (ECM remodeling is a critical step of many biological and pathological processes. However, most of the studies to date lack a quantitative method to measure ECM remodeling at a scale comparable to cell size. Here, we applied image spatial correlation to collagen second harmonic generation (SHG images to quantitatively evaluate the degree of collagen remodeling by cells. We propose a simple statistical method based on spatial correlation functions to determine the size of high collagen density area around cells. We applied our method to measure collagen remodeling by two breast cancer cell lines (MDA-MB-231 and MCF-7, which display different degrees of invasiveness, and a fibroblast cell line (NIH/3T3. We found distinct collagen compaction levels of these three cell lines by applying the spatial correlation method, indicating different collagen remodeling ability. Furthermore, we quantitatively measured the effect of Latrunculin B and Marimastat on MDA-MB-231 cell line collagen remodeling ability and showed that significant collagen compaction level decreases with these treatments.

  6. Denervation in Femoral Artery-Ligated Hindlimbs Diminishes Ischemic Recovery Primarily via Impaired Arteriogenesis

    OpenAIRE

    Cen, Yinghuan; Liu, Junfeng; Qin, Yuansen; Liu, Ruiming; Wang, Huijin; Zhou, Yu; Wang, Shenming; Hu, Zuojun

    2016-01-01

    Aims Multiple factors regulate arteriogenesis. Peripheral nerves play a crucial role in vascular remodeling, but the function of peripheral nerves during arteriogenesis is obscure. Our study investigated the contribution of denervation to arteriogenesis during post-ischemic recovery from hindlimb femoral artery ligation. Methods and Results Sprague-Dawley rats were randomly allocated into four groups of normal control (NC), hindlimb ischemia (HI), hindlimb ischemia with denervation (HID) and ...

  7. Characterization of proximal pulmonary arterial cells from chronic thromboembolic pulmonary hypertension patients

    Directory of Open Access Journals (Sweden)

    Quarck Rozenn

    2012-03-01

    Full Text Available Abstract Background Chronic thromboembolic pulmonary hypertension (CTEPH is associated with proximal pulmonary artery obstruction and vascular remodeling. We hypothesized that pulmonary arterial smooth muscle (PASMC and endothelial cells (PAEC may actively contribute to remodeling of the proximal pulmonary vascular wall in CTEPH. Our present objective was to characterize PASMC and PAEC from large arteries of CTEPH patients and investigate their potential involvement in vascular remodeling. Methods Primary cultures of proximal PAEC and PASMC from patients with CTEPH, with non-thromboembolic pulmonary hypertension (PH and lung donors have been established. PAEC and PASMC have been characterized by immunofluorescence using specific markers. Expression of smooth muscle specific markers within the pulmonary vascular wall has been studied by immunofluorescence and Western blotting. Mitogenic activity and migratory capacity of PASMC and PAEC have been investigated in vitro. Results PAEC express CD31 on their surface, von Willebrand factor in Weibel-Palade bodies and take up acetylated LDL. PASMC express various differentiation markers including α-smooth muscle actin (α-SMA, desmin and smooth muscle myosin heavy chain (SMMHC. In vascular tissue from CTEPH and non-thromboembolic PH patients, expression of α-SMA and desmin is down-regulated compared to lung donors; desmin expression is also down-regulated in vascular tissue from CTEPH compared to non-thromboembolic PH patients. A low proportion of α-SMA positive cells express desmin and SMMHC in the neointima of proximal pulmonary arteries from CTEPH patients. Serum-induced mitogenic activity of PAEC and PASMC, as well as migratory capacity of PASMC, were increased in CTEPH only. Conclusions Modified proliferative and/or migratory responses of PASMC and PAEC in vitro, associated to a proliferative phenotype of PASMC suggest that PASMC and PAEC could contribute to proximal vascular remodeling in CTEPH.

  8. In vivo and in vitro measurements of pulmonary arterial stiffness: A brief review

    OpenAIRE

    Tian, Lian; Chesler, Naomi C.

    2012-01-01

    During the progression of pulmonary hypertension (PH), proximal pulmonary arteries (PAs) undergo remodeling such that they become thicker and the elastic modulus increases. Both of these changes increase the vascular stiffness. The increase in pulmonary vascular stiffness contributes to increased right ventricular (RV) afterload, which causes RV hypertrophy and eventually failure. Studies have found that proximal PA stiffness or its inverse, compliance, is strongly related to morbidity and mo...

  9. Hypertrophy and hyperplasia of smooth muscle cells of small intramyocardial arteries in spontaneously hypertensive rats.

    Science.gov (United States)

    Amann, K; Gharehbaghi, H; Stephen, S; Mall, G

    1995-01-01

    Hearts of stroke-prone spontaneously hypertensive rats (SHR) were investigated by means of stereology and were compared with those of normotensive. Wistar-Kyoto controls. At the age of 9 months, hypertensive rats showed cardiac hypertrophy, marked myocardial fibrosis, activation of nonvascular interstitium, focal myocytial degeneration, reduction of capillarization, and microarteriopathy of small intramyocardial arteries. Stereologically, a significant increase in the total left ventricular arterial wall volume (+180% versus controls) was found in SHR hearts. By using new stereological techniques, the orientator and the nucleator, we investigated whether this significant increase in total left ventricular arterial wall volume was due to hyperplasia of smooth muscle cells in addition to the process of vascular smooth muscle cell hypertrophy that is common in SHR. Additionally, the nuclear size and ratio of cell volume to nuclear volume were determined using another new stereological technique, the selector. The stereological data indicate a significant increase in mean cell and nuclear volumes as well as in the total number of left ventricular arterial smooth muscle cells of SHR. Additionally, the total length of intramyocardial arteries was also significantly increased in hypertensive rats. The volume and number of arterial smooth muscle cells per arterial length were significantly (P < .001 and P < .05, respectively) higher in SHR than in normotensive controls. Thus, we conclude that hypertrophy and hyperplasia of smooth muscle cells are involved in intramyocardial arterial growth processes in hypertensive heart remodeling.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7843743

  10. Influence of nutrient restriction and melatonin supplementation of pregnant ewes on maternal and fetal pancreatic digestive enzymes and insulin-containing clusters.

    Science.gov (United States)

    Keomanivong, F E; Lemley, C O; Camacho, L E; Yunusova, R; Borowicz, P P; Caton, J S; Meyer, A M; Vonnahme, K A; Swanson, K C

    2016-03-01

    Primiparous ewes (n=32) were assigned to dietary treatments in a 2×2 factorial arrangement to determine effects of nutrient restriction and melatonin supplementation on maternal and fetal pancreatic weight, digestive enzyme activity, concentration of insulin-containing clusters and plasma insulin concentrations. Treatments consisted of nutrient intake with 60% (RES) or 100% (ADQ) of requirements and melatonin supplementation at 0 (CON) or 5 mg/day (MEL). Treatments began on day 50 of gestation and continued until day 130. On day 130, blood was collected under general anesthesia from the uterine artery, uterine vein, umbilical artery and umbilical vein for plasma insulin analysis. Ewes were then euthanized and the pancreas removed from the ewe and fetus, trimmed of mesentery and fat, weighed and snap-frozen until enzyme analysis. In addition, samples of pancreatic tissue were fixed in 10% formalin solution for histological examination including quantitative characterization of size and distribution of insulin-containing cell clusters. Nutrient restriction decreased (P⩽0.001) maternal pancreatic mass (g) and α-amylase activity (U/g, kU/pancreas, U/kg BW). Ewes supplemented with melatonin had increased pancreatic mass (P=0.03) and α-amylase content (kU/pancreas and U/kg BW). Melatonin supplementation decreased (P=0.002) maternal pancreatic insulin-positive tissue area (relative to section of tissue), and size of the largest insulin-containing cell cluster (P=0.04). Nutrient restriction decreased pancreatic insulin-positive tissue area (P=0.03) and percent of large (32 001 to 512 000 µm2) and giant (⩾512 001 µm2) insulin-containing cell clusters (P=0.04) in the fetus. Insulin concentrations in plasma from the uterine vein, umbilical artery and umbilical vein were greater (P⩽0.01) in animals receiving 100% requirements. When comparing ewes to fetuses, ewes had a greater percentage of medium insulin-containing cell clusters (2001 to 32 000 µm2) while fetuses

  11. Hemodynamics and right-ventricle functional characteristics of a swine carotid artery-jugular vein shunt model of pulmonary arterial hypertension: An 18-month experimental study.

    Science.gov (United States)

    Wu, Ji; Luo, Xiaoju; Huang, Yuanyuan; He, Yun; Li, Zhixian

    2015-10-01

    The continuous changes in pulmonary hemodynamic properties and right ventricular (RV) function in pulmonary arterial hypertension (PAH) have not been fully characterized in large animal model of PAH induced by a carotid artery-jugular vein shunt. A minipig model of PAH was induced by a surgical anastomosis between the left common carotid artery and the left jugular vein. The model was validated by catheter examination and pathologic analyses, and the hemodynamic features and right-ventricle functional characteristics of the model were continuously observed by Doppler echocardiography. Of the 45 minipigs who received the surgery, 27 survived and were validated as models of PAH, reflected by mean pulmonary artery pressure ≥25 mmHg, and typical pathologic changes of pulmonary arterial remodeling and RV fibrosis. Non-invasive indices of pulmonary hemodynamics (pulmonary artery accelerating time and its ratio to RV ventricular ejection time) were temporarily increased, then reduced later, similar to changes in tricuspid annular displacement. The Tei index of the RV was elevated, indicating a progressive impairment in RV function. Surgical anastomosis between carotid artery and jugular vein in a minipig is effective to establish PAH, and non-invasive hemodynamic and right-ventricle functional indices measured by Doppler echocardiography may be used as early indicators of PAH. PMID:25595189

  12. Insulin delivery methods: Past, present and future.

    Science.gov (United States)

    Shah, Rima B; Patel, Manhar; Maahs, David M; Shah, Viral N

    2016-01-01

    Many patients with advanced type 2 diabetes mellitus (T2DM) and all patients with T1DM require insulin to keep blood glucose levels in the target range. The most common route of insulin administration is subcutaneous insulin injections. There are many ways to deliver insulin subcutaneously such as vials and syringes, insulin pens, and insulin pumps. Though subcutaneous insulin delivery is the standard route of insulin administration, it is associated with injection pain, needle phobia, lipodystrophy, noncompliance and peripheral hyperinsulinemia. Therefore, the need exists for delivering insulin in a minimally invasive or noninvasive and in most physiological way. Inhaled insulin was the first approved noninvasive and alternative way to deliver insulin, but it has been withdrawn from the market. Technologies are being explored to make the noninvasive delivery of insulin possible. Some of the routes of insulin administration that are under investigation are oral, buccal, nasal, peritoneal and transdermal. This review article focuses on the past, present and future of various insulin delivery techniques. This article has focused on different possible routes of insulin administration with its advantages and limitation and possible scope for the new drug development. PMID:27014614

  13. Pulmonary Arterial Stiffness: Toward a New Paradigm in Pulmonary Arterial Hypertension Pathophysiology and Assessment.

    Science.gov (United States)

    Schäfer, Michal; Myers, Cynthia; Brown, R Dale; Frid, Maria G; Tan, Wei; Hunter, Kendall; Stenmark, Kurt R

    2016-01-01

    Stiffening of the pulmonary arterial bed with the subsequent increased load on the right ventricle is a paramount feature of pulmonary hypertension (PH). The pathophysiology of vascular stiffening is a complex and self-reinforcing function of extracellular matrix remodeling, driven by recruitment of circulating inflammatory cells and their interactions with resident vascular cells, and mechanotransduction of altered hemodynamic forces throughout the ventricular-vascular axis. New approaches to understanding the cell and molecular determinants of the pathophysiology combine novel biopolymer substrates, controlled flow conditions, and defined cell types to recapitulate the biomechanical environment in vitro. Simultaneously, advances are occurring to assess novel parameters of stiffness in vivo. In this comprehensive state-of-art review, we describe clinical hemodynamic markers, together with the newest translational echocardiographic and cardiac magnetic resonance imaging methods, to assess vascular stiffness and ventricular-vascular coupling. Finally, fluid-tissue interactions appear to offer a novel route of investigating the mechanotransduction processes and disease progression. PMID:26733189

  14. Cardiovascular effects of basal insulins.

    Science.gov (United States)

    Mannucci, Edoardo; Giannini, Stefano; Dicembrini, Ilaria

    2015-01-01

    Basal insulin is an important component of treatment for both type 1 and type 2 diabetes. One of the principal aims of treatment in patients with diabetes is the prevention of diabetic complications, including cardiovascular disease. There is some evidence, although controversial, that attainment of good glycemic control reduces long-term cardiovascular risk in both type 1 and type 2 diabetes. The aim of this review is to provide an overview of the potential cardiovascular safety of the different available preparations of basal insulin. Current basal insulin (neutral protamine Hagedorn [NPH], or isophane) and basal insulin analogs (glargine, detemir, and the more recent degludec) differ essentially by various measures of pharmacokinetic and pharmacodynamic effects in the bloodstream, presence and persistence of peak action, and within-subject variability in the glucose-lowering response. The currently available data show that basal insulin analogs have a lower risk of hypoglycemia than NPH human insulin, in both type 1 and type 2 diabetes, then excluding additional harmful effects on the cardiovascular system mediated by activation of the adrenergic system. Given that no biological rationale for a possible difference in cardiovascular effect of basal insulins has been proposed so far, available meta-analyses of publicly disclosed randomized controlled trials do not show any signal of increased risk of major cardiovascular events between the different basal insulin analogs. However, the number of available cardiovascular events in these trials is very small, preventing any clear-cut conclusion. The results of an ongoing clinical trial comparing glargine and degludec with regard to cardiovascular safety will provide definitive evidence. PMID:26203281

  15. Transcatheter arterial infusing chemotherapy for advanced malignant pancreatic islet cell tumors: four cases report

    International Nuclear Information System (INIS)

    Objective: To explore the clinical efficacy of transcatheter arterial infusion (TAI) chemotherapy for advanced malignant pancreatic islet cell tumors. Methods: Four patients (3 malignant insulin tumors, 1 non-functional malignant pancreatic islet cell tumor) with unresectable advanced malignant tumors were carried out TAI via celiac artery. The three malignant insulin tumors with multiple hepatic metastases were further performed with transcatheter arterial chemoembolization (TACE). The therapeutic cycles were repeated with intervals of 1-2 months. Results: Eleven therapeutic cycles (mean 2.8)were accomplished in 4 cases. Follow-up for 2-8 months, the clinical PR were achieved in three cases, furthermore with SD in one case. The clinical uprising blood glucose became normal in all three cases, and the abdominal distention and bellyache were relieved in the patient with non-functional malignant pancreatic islet cell tumor. No serious adverse effects occurred. Conclusions: TAI for unresectable advanced malignant pancreatic islet cell tumors is safe and effective. (authors)

  16. Exogenous spermine inhibits the proliferation of human pulmonary artery smooth muscle cells caused by chemically-induced hypoxia via the suppression of the ERK1/2- and PI3K/AKT-associated pathways

    OpenAIRE

    WEI, CAN; Li, Hong-zhu; Wang, Yue-Hong; Peng, Xue; SHAO, HONG-JIANG; Li, Hong-xia; Bai, Shu-zhi; Lu, Xiao-Xiao; Wu, Ling-Yun; Wang, Rui; Xu, Chang-qing

    2015-01-01

    Pulmonary vascular remodeling is a significant pathological feature of hypoxia-induced pulmonary hypertension (HPH), while pulmonary artery smooth muscle cell (PASMC) proliferation plays a leading role in pulmonary vascular remodeling. Spermine (Sp), a polyamine, plays a critical role in periodic cell proliferation and apoptosis. The present study was conducted to observe the association between hypoxia-induced PASMC proliferation and polyamine metabolism, and to explore the effects of exogen...

  17. A retrospective database analysis of insulin use patterns in insulin-naïve patients with type 2 diabetes initiating basal insulin or mixtures

    OpenAIRE

    Bonafede, Machaon MK; Kalsekar, Anupama; Pawaskar, Manjiri; Ruiz, Kimberly M; Torres, Amelito M; Kelly, Karen R.; Curkendall, Suellen M

    2010-01-01

    Objective: To describe insulin persistence among patients with type 2 diabetes initiating insulin therapy with basal insulin or insulin mixtures and determine factors associated with nonpersistence. Research design and methods: The Thomson Reuters MarketScan® databases were used to retrospectively analyze insulin-naïve patients with type 2 diabetes by initiating insulin therapy. Insulin use was described using a variety of measures. The persistence to insulin was described using both a gap-ba...

  18. Diabetes due to secretion of a structurally abnormal insulin (insulin Wakayama). Clinical and functional characteristics of [LeuA3] insulin.

    OpenAIRE

    Nanjo, K; Sanke, T; Miyano, M; Okai, K.; Sowa, R; Kondo, M.; Nishimura, S; Iwo, K; Miyamura, K; Given, B D

    1986-01-01

    We have identified a non-insulin-dependent diabetic patient with fasting hyperinsulinemia (90 microU/ml), an elevated insulin:C-peptide molar ratio (1.68; normal, 0.05-0.20), normal insulin counterregulatory hormone levels, and an adequate response to exogenously administered insulin. Insulin-binding antibodies were absent from serum, erythrocyte insulin receptor binding was normal, and greater than 90% of circulating immunoreactive insulin coeluted with 125I-labeled insulin on gel filtration...

  19. Reduced immunoreactivities of B-type natriuretic peptide in pulmonary arterial hypertension rats after ranolazine treatment.

    Science.gov (United States)

    Lee, Jae Chul; Kim, Kwan Chang; Choe, Soo Young; Hong, Young Mi

    2016-03-01

    Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by sustained increase in the pulmonary arterial pressure and excessive thickening and remodeling of the distal small pulmonary arteries. During disease progression, structural remodeling of the right ventricular (RV) impairs pump function, creates pro-arrhythmic substrates and triggers for arrhythmias. Notably, RV failure and lethal arrhythmias are major contributors to cardiac death in PAH that are not directly addressed by currently available therapies. Ranolazine (RAN) is an anti-anginal, anti-ischemic drug that has cardioprotective effects of heart dysfunction. RAN also has anti-arrhythmic effects due to inhibition of the late sodium current in cardiomyocytes. Therefore, we hypothesized that RAN could reduce the mal-adaptive structural remodeling of the RV, and prevent triggered ventricular arrhythmias in the monocrotaline-induced rat model of PAH. RAN reduced ventricular hypertrophy, reduced levels of B-type natriuretic peptide, and decreased the expression of fibrosis. In addition, RAN prevented cardiovascular death in rat model of PAH. These results support the notion that RAN can improve the functional properties of the RV, highlighting its potential benefits in the setting of heart impairment. PMID:27051563

  20. Diabetes, insulin and cancer risk

    Directory of Open Access Journals (Sweden)

    Xi-Lin Yang

    2012-01-01

    Full Text Available There is a consensus that both type 1 and type 2 diabetes are associated with a spectrum of cancers but the underlying mechanisms are largely unknown. On the other hand, there are ongoing debates about the risk association of insulin use with cancer. We have briefly reviewed recent related research on exploration of risk factors for cancer and pharmacoepidemiological investigations into drug use in diabetes on the risk of cancer, as well as the current understanding of metabolic pathways implicated in intermediary metabolism and cellular growth. Based on the novel findings from the Hong Kong Diabetes Registry and consistent experimental evidence, we argue that use of insulin to control hyperglycemia is unlikely to contribute to increased cancer risk and that dysregulations in the AMP-activated protein kinase pathway due to reduced insulin action and insulin resistance, the insulin-like growth factor-1 (IGF-1-cholesterol synthesis pathway and renin-angiotensin system, presumably due to reduced insulin secretion and hyperglycemia, may play causal roles in the increased risk of cancer in diabetes. Further exploration into the possible causal relationships between abnormalities of these pathways and the risk of cancer in diabetes is warranted.