WorldWideScience

Sample records for pioglitazone enhances collateral

  1. Enhancing pancreatic Beta-cell regeneration in vivo with pioglitazone and alogliptin.

    Directory of Open Access Journals (Sweden)

    Hao Yin

    Full Text Available AIMS/HYPOTHESIS: Pancreatic beta-cells retain limited ability to regenerate and proliferate after various physiologic triggers. Identifying therapies that are able to enhance beta-cell regeneration may therefore be useful for the treatment of both type 1 and type 2 diabetes. METHODS: In this study we investigated endogenous and transplanted beta-cell regeneration by serially quantifying changes in bioluminescence from beta-cells from transgenic mice expressing firefly luciferase under the control of the mouse insulin I promoter. We tested the ability of pioglitazone and alogliptin, two drugs developed for the treatment of type 2 diabetes, to enhance beta-cell regeneration, and also defined the effect of the immunosuppression with rapamycin and tacrolimus on transplanted islet beta mass. RESULTS: Pioglitazone is a stimulator of nuclear receptor peroxisome proliferator-activated receptor gamma while alogliptin is a selective dipeptidyl peptidase IV inhibitor. Pioglitazone alone, or in combination with alogliptin, enhanced endogenous beta-cell regeneration in streptozotocin-treated mice, while alogliptin alone had modest effects. In a model of syngeneic islet transplantation, immunosuppression with rapamycin and tacrolimus induced an early loss of beta-cell mass, while treatment with insulin implants to maintain normoglycemia and pioglitazone plus alogliptin was able to partially promote beta-cell mass recovery. CONCLUSIONS/INTERPRETATION: These data highlight the utility of bioluminescence for serially quantifying functional beta-cell mass in living mice. They also demonstrate the ability of pioglitazone, used either alone or in combination with alogliptin, to enhance regeneration of endogenous islet beta-cells as well as transplanted islets into recipients treated with rapamycin and tacrolimus.

  2. Enhancement of canine coronary collateral flow by nafazatrom.

    Science.gov (United States)

    Fiedler, V B; Mardin, M

    1986-11-04

    The ability of oral nafazatrom treatment (10 mg/kg) 2 h preceding occlusion of the left anterior descending coronary artery for 6 h to limit expansion of myocardial injury was studied in anaesthetized canine hearts. Collateral blood flow was obtained with a load line analysis, employing aortic pressure, post-stenotic coronary pressure, and retrograde coronary flow from the occluded vessel. Contractile changes in the subendocardial ischemic perfused muscles were measured with ultrasonic techniques. Infarct size was determined post-mortem by a biochemical staining method and excision of necrosis. Post-stenotic coronary pressure was slightly below aortic pressure in both groups before coronary occlusion, and fell to 29 and 27% of aortic pressure in vehicle- and drug-treated hearts, respectively, after the insult. Retrograde flow was 2.4 +/- 0.6 vs. 4.1 +/- 0.7 ml/min in tylose- or nafazatrom-treated hearts. Collateral flow amounted to 1.5 +/- 0.06 vs. 2.5 +/- 0.04 ml/min in controls and drug-protected hearts. Contractility (dP/dtmax) and the %-segment shortening were greater in the ischaemic myocardium after nafazatrom treatment. Infarct size was 38 +/- 5.2 vs. 17 +/- 3.4 g/100 g left ventricle in the vehicle controls and nafazatrom group, respectively. Nafazatrom reduced infarct size by 46%. Besides other mechanisms, this was due to improved %-segment shortening and increased periinfarction collateral blood supply to jeopardized but viable myocardium. The drug may be of value in ischaemic heart disease as shown by the enhanced regional myocardial perfusion and improved contractility.

  3. Retrospective analysis of intravertebral collateral enhancement in patients with central venous obstruction

    Energy Technology Data Exchange (ETDEWEB)

    Simeone, F.J.; Chang, Connie Y.; Huang, Ambrose J.; Kattapuram, Susan V.; Bredella, Miriam A.; Torriani, Martin [Massachusetts General Hospital and Harvard Medical School, Division of Musculoskeletal Imaging and Intervention, Department of Radiology, Boston, MA (United States); Bennett, Debbie L. [Saint Louis University School of Medicine, Department of Radiology, Saint Louis, MO (United States)

    2016-02-15

    To compare prevalence and patterns of intravertebral collateral enhancement in patients with and without central venous obstruction (CVO). Chest CTs performed between 1/1/2000 and 12/15/2012 with reports containing terms indicating CVO were identified. All contrast enhanced CTs were examined for the presence of CVO and collateral venous pathways. If intravertebral collateral enhancement was present, the pattern was recorded as nodular, linear, or both. In 209 suspected cases of CVO, 53 (25 %) were confirmed with obstruction and 156 (75 %) were without obstruction. In patients with CVO, 47 % (25/53) demonstrated collateral venous flow through an intravertebral marrow pathway compared to 5 % (8/156) of patients without CVO (P < 0.0001). The most common level of enhancement was the upper thoracic spine, involving only the vertebral body. Nodular, linear, and combined nodular-linear enhancement patterns were seen with similar frequency. Nodular intravertebral collateral enhancement was mistaken for sclerotic metastases in 33 % (3/9) of cases. Intravertebral collateral enhancement was seen in almost half the patients with CVO and when nodular enhancement is present, it is important to differentiate between metastatic lesions and enhancement related to CVO. (orig.)

  4. Pioglitazone enhances mitochondrial biogenesis and ribosomal protein biosynthesis in skeletal muscle in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Skov, Vibe; Glintborg, Dorte; Knudsen, Steen

    2008-01-01

    Insulin resistance is a common metabolic abnormality in women with PCOS and leads to an elevated risk of type 2 diabetes. Studies have shown that thiazolidinediones (TZDs) improve metabolic disturbances in PCOS patients. We hypothesized that the effect of TZDs in PCOS is, in part, mediated...... by changes in the transcriptional profile of muscle favoring insulin sensitivity. Using Affymetrix microarrays, we examined the effect of pioglitazone (30 mg/day for 16 weeks) on gene expression in skeletal muscle of 10 obese women with PCOS metabolically characterized by a euglycemic-hyperinsulinemic clamp....... Moreover, we explored gene expression changes between these PCOS patients before treatment and 13 healthy women. Treatment with pioglitazone improved insulin-stimulated glucose metabolism and plasma adiponectin, and reduced fasting serum insulin (all P

  5. Collateral Ventilation to Congenital Hyperlucent Lung Lesions Assessed on Xenon-Enhanced Dynamic Dual-Energy CT: an Initial Experience

    Energy Technology Data Exchange (ETDEWEB)

    Goo, Hyun Woo; Yang, Dong Hyun; Kim, Nam Kug; Park, Seung Il; Kim, Dong Kwan; Kim, Ellen Ai Rhan [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2011-02-15

    We wanted to evaluate the resistance to collateral ventilation in congenital hyperlucent lung lesions and to correlate that with the anatomic findings on xenon-enhanced dynamic dual-energy CT. Xenon-enhanced dynamic dual-energy CT was successfully and safely performed in eight children (median age: 5.5 years, 4 boys and 4 girls) with congenital hyperlucent lung lesions. Functional assessment of the lung lesions on the xenon map was done, including performing a time-xenon value curve analysis and assessing the amplitude of xenon enhancement (A) value, the rate of xenon enhancement (K) value and the time of arrival value. Based on the A value, the lung lesions were categorized into high or low (A value > 10 Hounsfi eld unit [HU]) resistance to collateral ventilation. In addition, the morphologic CT findings of the lung lesions, including cyst, mucocele and an accessory or incomplete fissure, were assessed on the weighted-average CT images. The xenon-enhanced CT radiation dose was estimated. Five of the eight lung lesions were categorized into the high resistance group and three lesions were categorized into the low resistance group. The A and K values in the normal lung were higher than those in the low resistance group. The time of arrival values were delayed in the low resistance group. Cysts were identified in five lesions, mucocele in four, accessory fissure in three and incomplete fissure in two. Either cyst or an accessory fissure was seen in four of the five lesions showing high resistance to collateral ventilation. The xenon-enhanced CT radiation dose was 2.3 {+-} 0.6 mSv. Xenon-enhanced dynamic dual-energy CT can help visualize and quantitate various degrees of collateral ventilation to congenital hyperlucent lung lesions in addition to assessing the anatomic details of the lung

  6. Investigation of the antibacterial activity of pioglitazone

    Directory of Open Access Journals (Sweden)

    Alzoubi KH

    2011-09-01

    Full Text Available Majed M Masadeh1, Nizar M Mhaidat2, Sayer I Al-Azzam2, Karem H Alzoubi21Department of Pharmaceutical Technology; 2Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, JordanPurpose: To evaluate the antibacterial potential of pioglitazone, a member of the thiazolidinediones class of drugs, against Gram-positive (Streptococcus pneumoniae and Gram-negative (Escherichia coli and Klebsiella pneumoniae bacteria.Methods: Susceptibility testing was done using the antibiotic disk diffusion method and the minimal inhibitory concentration (MIC of pioglitazone was measured according to the broth micro incubation standard method.Results: Pioglitazone induced a dose-dependent antibacterial activity in which the optimal concentration was 80 µM. Furthermore, results indicated that while E. coli was sensitive (MIC = 31.25 ± 3.87 mg/L to pioglitazone-induced cytotoxicity, S. pneumoniae and K. pneumoniae were resistant (MIC = 62.5 ± 3.77 mg/L and MIC = 62.5 ± 4.14 mg/L, respectively. Moreover, pretreatment of bacteria with a suboptimal concentration of pioglitazone (40 µM before adding amoxicillin, cephalexin, co-trimoxazole, or ciprofloxacin enhanced the antibacterial activity of all agents except co-trimoxazole. This enhancing effect was particularly seen against K. pneumoniae.Conclusion: These results indicate the possibility of a new and potentially important pioglitazone effect and the authors’ ongoing studies aim to illustrate the mechanism(s by which this antibacterial effect is induced.Keywords: pioglitazone, susceptibility testing, antibiotics, diabetes 

  7. Sphingosine-1-Phosphate Receptor-1 Selective Agonist Enhances Collateral Growth and Protects against Subsequent Stroke.

    Directory of Open Access Journals (Sweden)

    Masahiko Ichijo

    Full Text Available Collateral growth after acute occlusion of an intracranial artery is triggered by increasing shear stress in preexisting collateral pathways. Recently, sphingosine-1-phosphate receptor-1 (S1PR1 on endothelial cells was reported to be essential in sensing fluid shear stress. Here, we evaluated the expression of S1PR1 in the hypoperfused mouse brain and investigated the effect of a selective S1PR1 agonist on leptomeningeal collateral growth and subsequent ischemic damage after focal ischemia.In C57Bl/6 mice (n = 133 subjected to unilateral common carotid occlusion (CCAO and sham surgery. The first series examined the time course of collateral growth, cell proliferation, and S1PR1 expression in the leptomeningeal arteries after CCAO. The second series examined the relationship between pharmacological regulation of S1PR1 and collateral growth of leptomeningeal anastomoses. Animals were randomly assigned to one of the following groups: LtCCAO and daily intraperitoneal (i.p. injection for 7 days of an S1PR1 selective agonist (SEW2871, 5 mg/kg/day; sham surgery and daily i.p. injection for 7 days of SEW2871 after surgery; LtCCAO and daily i.p. injection for 7 days of SEW2871 and an S1PR1 inverse agonist (VPC23019, 0.5 mg/kg; LtCCAO and daily i.p. injection of DMSO for 7 days after surgery; and sham surgery and daily i.p. injection of DMSO for 7 days. Leptomeningeal anastomoses were visualized 14 days after LtCCAO by latex perfusion method, and a set of animals underwent subsequent permanent middle cerebral artery occlusion (pMCAO 7 days after the treatment termination. Neurological functions 1 hour, 1, 4, and 7 days and infarction volume 7 days after pMCAO were evaluated.In parallel with the increase in S1PR1 mRNA levels, S1PR1 expression colocalized with endothelial cell markers in the leptomeningeal arteries, increased markedly on the side of the CCAO, and peaked 7 days after CCAO. Mitotic cell numbers in the leptomeningeal arteries increased after

  8. Enhanced collateral growth by double transplantation of gene-nucleofected fibroblasts in ischemic hindlimb of rats.

    Directory of Open Access Journals (Sweden)

    Ziyang Zhang

    Full Text Available BACKGROUND: Induction of neovascularization by releasing therapeutic growth factors is a promising application of cell-based gene therapy to treat ischemia-related problems. In the present study, we have developed a new strategy based on nucleofection with alternative solution and cuvette to promote collateral growth and re-establishment of circulation in ischemic limbs using double transplantation of gene nucleofected primary cultures of fibroblasts, which were isolated from rat receiving such therapy. METHODS AND RESULTS: Rat dermal fibroblasts were nucleofected ex vivo to release bFGF or VEGF165 in a hindlimb ischemia model in vivo. After femoral artery ligation, gene-modified cells were injected intramuscularly. One week post injection, local confined plasmid expression and transient distributions of the plasmids in other organs were detected by quantitative PCR. Quantitative micro-CT analyses showed improvements of vascularization in the ischemic zone (No. of collateral vessels via micro CT: 6.8±2.3 vs. 10.1±2.6; p<0.05. Moreover, improved collateral proliferation (BrdU incorporation: 0.48±0.05 vs. 0.57±0.05; p<0.05 and increase in blood perfusion (microspheres ratio: gastrocnemius: 0.41±0.10 vs. 0.50±0.11; p<0.05; soleus ratio: soleus: 0.42±0.08 vs. 0.60±0.08; p<0.01 in the lower hindlimb were also observed. CONCLUSIONS: These results demonstrate the feasibility and effectiveness of double transplantation of gene nucleofected primary fibroblasts in producing growth factors and promoting the formation of collateral circulation in ischemic hindlimb, suggesting that isolation and preparation of gene nucleofected cells from individual accepting gene therapy may be an alternative strategy for treating limb ischemia related diseases.

  9. Combined use of bFGF and GDF-5 enhances the healing of medial collateral ligament injury

    Energy Technology Data Exchange (ETDEWEB)

    Saiga, Kenta [Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikatacho, Kitaku, Okayama 700-8558 (Japan); Furumatsu, Takayuki, E-mail: matino@md.okayama-u.ac.jp [Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikatacho, Kitaku, Okayama 700-8558 (Japan); Yoshida, Aki; Masuda, Shin; Takihira, Shota [Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikatacho, Kitaku, Okayama 700-8558 (Japan); Abe, Nobuhiro [Department of Intelligent Orthopaedic System Development, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikatacho, Kitaku, Okayama 700-8558 (Japan); Ozaki, Toshifumi [Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikatacho, Kitaku, Okayama 700-8558 (Japan)

    2010-11-12

    Research highlights: {yields} bFGF/GDF-5 treatment increases cellular proliferation and migration of MCL fibroblasts. {yields} bFGF/GDF-5 hydrogels stimulate the healing of MCL injury in vivo. {yields} bFGF/GDF-5 hydrogels stimulate Col1a1 expression and type I collagen synthesis. {yields} Combined use of bFGF/GDF-5 enhances MCL healing. -- Abstract: Basic fibroblast growth factor (bFGF) and growth and differentiation factor (GDF)-5 stimulate the healing of medial collateral ligament (MCL) injury. However, the effect of isolated and combined use of bFGF/GDF-5 remains still unclear. We investigated cellular proliferation and migration responding to bFGF/GDF-5 using rabbit MCL fibroblasts. Rabbit MCL injury was treated by bFGF and/or GDF-5 with peptide hydrogels. Gene expression and deposition of collagens in healing tissues were evaluated. bFGF/GDF-5 treatment additively enhanced cell proliferation and migration. bFGF/GDF-5 hydrogels stimulated Col1a1 expression without increasing Col3a1 expression. Combined use of bFGF/GDF-5 stimulated type I collagen deposition and the reorganization of fiber alignment, and induced better morphology of fibroblasts in healing MCLs. Our study indicates that combined use of bFGF/GDF-5 might enhance MCL healing by increasing proliferation and migration of MCL fibroblasts, and by regulating collagen synthesis and connective fiber alignment.

  10. Pioglitazone promotes preadipocyte proliferation by downregulating p16{sup Ink4a}

    Energy Technology Data Exchange (ETDEWEB)

    Hasan, Arif U. [Department of Cardiorenal Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793 (Japan); Ohmori, Koji, E-mail: komori@med.kagawa-u.ac.jp [Department of Cardiorenal Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793 (Japan); Hashimoto, Takeshi [Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793 (Japan); Kamitori, Kazuyo; Hirata, Yuko [Department of Cell Physiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793 (Japan); Ishihara, Yasuhiro; Okamoto, Naoko; Noma, Takahisa [Department of Cardiorenal Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793 (Japan); Kosaka, Hiroaki [Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793 (Japan); Tokuda, Masaaki [Department of Cell Physiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793 (Japan); Kohno, Masakazu [Department of Cardiorenal Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793 (Japan)

    2011-07-29

    Highlights: {yields} Mechanisms for preadipocyte hyperplasia by pioglitazone, a PPAR{gamma} agonist, are shown. {yields} Pioglitazone promotes cell-cycle of 3T3-L1 preadipocytes and increases their number. {yields} Pioglitazone downregulates a cyclin dependent kinase inhibitor, p16{sup Ink4a}. {yields} PPAR{gamma} transrepresses p16{sup Ink4a} gene in preadipocytes, which pioglitazone enhances. -- Abstract: Pioglitazone, a synthetic ligand of peroxisome proliferator-activated receptor (PPAR){gamma}, causes preadipocyte proliferation through a mechanism which still remains elusive. Here, to address the mechanism, we investigated the effects of PPAR{gamma} and pioglitazone on the kinetics of cyclin-dependent kinase inhibitors, especially with p16{sup Ink4a} (p16) centered, by employing 3T3-L1 preadipocytes. Pioglitazone promoted preadipocyte proliferation by increasing S and G{sub 2}/M cell-cycle entry, which was accompanied by decreased p16 mRNA expression. PPAR{gamma} overexpression along with the luciferase reporter assay confirmed that PPAR{gamma} was crucial for the downregulation of p16 mRNA transcription, and that the action was augmented by pioglitazone. Thus, pioglitazone exerted cell-cycle dependent promoting effect on preadipocyte proliferation, of which mechanisms include p16-downregulation through PPAR{gamma}.

  11. Prominent porto-systemic collateral pathways in patients with portal hypertension: demonstration by gadolinium-enhanced magnetic resonance angiography; Vias colaterais porto-sistemicas exuberantes em portadores de hipertensao portal: demonstracao pela angiografia por ressonancia magnetica com gadolinio

    Energy Technology Data Exchange (ETDEWEB)

    Caldana, Rogerio Pedreschi; Bezerra, Alexandre Araujo Sergio; Cecin, Alexnadre Oliveira; Souza, Luis Ronan Marques Ferreira de; Goldman, Susan Menasce; D' Ippolito, Giuseppe; Szejnfeld, Jacob [Universidade Federal de Sao Paulo (UNIFESP/EPM), Sao Paulo, SP (Brazil). Dept. de Diagnostico por Imagem]. E-mail: rogercal@uol.com.br

    2003-03-01

    To demonstrate the usefulness of gadolinium-enhanced magnetic resonance angiography in the evaluation of prominent porto-systemic collateral pathways. We reviewed the images from 40 patients with portal hypertension studied with gadolinium-enhanced magnetic resonance angiography and selected illustrative cases of prominent porto-systemic collateral pathways. The scans were performed using high field equipment (1.5 Tesla) and a 3 D volume technique. Image were obtained after intravenous injection of paramagnetic contrast media using a power injector. Magnetic resonance angiography demonstrated with precision the porto-systemic collateral pathways, particularly when investigating extensive territories or large vessels. The cases presented show the potential of this method in the investigation of patients with portal hypertension. Gadolinium-enhanced magnetic resonance angiography is a useful method for the evaluation of patients with portal hypertension and prominent collateral pathways. (author)

  12. The effect of pioglitazone on aldosterone and cortisol production in HAC15 human adrenocortical carcinoma cells.

    Science.gov (United States)

    Pan, Zhi-qiang; Xie, Ding; Choudhary, Vivek; Seremwe, Mutsa; Tsai, Ying-Ying; Olala, Lawrence; Chen, Xunsheng; Bollag, Wendy B

    2014-08-25

    Pioglitazone belongs to the class of drugs called thiazolidinediones (TZDs), which are widely used as insulin sensitizers in the treatment of diabetes. A major side effect of TZDs is fluid retention. The steroid hormone aldosterone also promotes sodium and fluid retention; however, the effect of pioglitazone on aldosterone production is controversial. We analyzed the effect of pioglitazone alone and in combination with angiotensin II (AngII) on the late rate-limiting step of adrenocortical steroidogenesis in human adrenocortical carcinoma HAC15 cells. Treatment with pioglitazone for 24 h significantly increased the expression of CYP11B2 and enhanced AngII-induced CYP11B2 expression. Despite the observed changes in mRNA levels, pioglitazone significantly inhibited AngII-induced aldosterone production and CYP11B2 protein levels. On the other hand, pioglitazone stimulated the expression of the unfolded protein response (UPR) marker DDIT3, with this effect occurring at early times and inhibitable by the PPARγ antagonist GW9962. The levels of DDIT3 (CHOP) and phospho-eIF2α (Ser51), a UPR-induced event that inhibits protein translation, were also increased. Thus, pioglitazone promotes CYP11B2 expression but nevertheless inhibits aldosterone production in AngII-treated HAC15 cells, likely by blocking global protein translation initiation through DDIT3 and phospho-eIF2α. In contrast, pioglitazone promoted AngII-induced CYP11B1 expression and cortisol production. Since cortisol enhances lipolysis, this result suggests the possibility that PPARs, activated by products of fatty acid oxidation, stimulate cortisol secretion to promote utilization of fatty acids during fasting. In turn, the ability of pioglitazone to stimulate cortisol production could potentially underlie the effects of this drug on fluid retention.

  13. Collateral ventilation quantification using xenon-enhanced dynamic dual-energy CT: Differences between canine and swine models of bronchial occlusion

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Ah; Goo, Jin Mo; Park, Sang Joon; Lee, Chang Hyun; Park, Chng Min [Dept. of Radiology, Seoul National University College of Medicine and Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul (Korea, Republic of)

    2015-06-15

    The aim of this study was to evaluate whether the difference in the degree of collateral ventilation between canine and swine models of bronchial obstruction could be detected by using xenon-enhanced dynamic dual-energy CT. Eight mongrel dogs and six pigs underwent dynamic dual-energy scanning of 64-slice dual-source CT at 12-second interval for 2-minute wash-in period (60% xenon) and at 24-second interval for 3-minute wash-out period with segmental bronchus occluded. Ventilation parameters of magnitude (A value), maximal slope, velocity (K value), and time-to-peak (TTP) enhancement were calculated from dynamic xenon maps using exponential function of Kety model. A larger difference in A value between parenchyma was observed in pigs than in dogs (absolute difference, -33.0 +/- 5.0 Hounsfield units [HU] vs. -2.8 +/- 7.1 HU, p = 0.001; normalized percentage difference, -79.8 +/- 1.8% vs. -5.4 +/- 16.4%, p = 0.0007). Mean maximal slopes in both periods in the occluded parenchyma only decreased in pigs (all p < 0.05). K values of both periods were not different (p = 0.892) in dogs. However, a significant (p = 0.027) difference was found in pigs in the wash-in period. TTP was delayed in the occluded parenchyma in pigs (p = 0.013) but not in dogs (p = 0.892). Xenon-ventilation CT allows the quantification of collateral ventilation and detection of differences between canine and swine models of bronchial obstruction.

  14. Pioglitazone Improves Mitochondrial Function in the Remnant Kidney and Protects against Renal Fibrosis in 5/6 Nephrectomized Rats

    Directory of Open Access Journals (Sweden)

    Li Sun

    2017-08-01

    Full Text Available Pioglitazone is a type of peroxisome proliferator-activated receptor γ (PPARγ agonist and has been demonstrated to be effective in chronic kidney diseases (CKD treatment. However, the underlying mechanism involved in the renoprotection of pioglitazone has not been fully revealed. In the present study, the renoprotective mechanism of pioglitazone was investigated in 5/6 nephrectomized (Nx rats and TGF-β1-exposed HK-2 cells. Pioglitazone attenuated renal injury and improved renal function, as examined by 24 h urinary protein, blood urea nitrogen and plasma creatinine in Nx rats. Renal fibrosis and enhanced expressions of profibrotic proteins TGF-β1, fibronectin and collagen I caused by Nx were significantly alleviated by pioglitazone. In addition, pioglitazone protected mitochondrial functions by stabilizing the mitochondrial membrane potential, inhibiting ROS generation, maintaining ATP production and the activities of complexes I and III, and preventing cytochrome C leakage from mitochondria. Pioglitazone also upregulated the expression levels of ATP synthase β, COX I and NDUFB8, which were downregulated in the kidney of Nx rats and TGF-β1-exposed HK-2 cells. Furthermore, pioglitazone increased fusion proteins Opa-1 and Mfn2 expressions and decreased fission protein Drp1 expression. The results imply that pioglitazone may exert the renoprotective effects through modulating mitochondrial electron transport chain and mitochondrial dynamics in CKD. Finally, these recoveries were completely or partly inhibited by GW9662, which suggests that these effects at least partly PPARγ dependent. This study provides evidence for the pharmacological mechanism of pioglitazone in the treatment of CKD.

  15. Current clinical evidence on pioglitazone pharmacogenomics

    Directory of Open Access Journals (Sweden)

    Marina eKawaguchi-Suzuki

    2013-11-01

    Full Text Available Pioglitazone is the most widely used thiazolidinedione and acts as an insulin-sensitizer through activation of the Peroxisome Proliferator-Activated Receptor-γ (PPARγ. Pioglitazone is approved for use in the management of type 2 diabetes mellitus, but its use in other therapeutic areas is increasing due to pleiotropic effects. In this hypothesis article, the current clinical evidence on pioglitazone pharmacogenomics is summarized and related to variability in pioglitazone response. How genetic variation in the human genome affects the pharmacokinetics and pharmacodynamics of pioglitazone was examined. For pharmacodynamic effects, hypoglycemic and anti-atherosclerotic effects, risks of fracture or edema, and the increase in body mass index in response to pioglitazone based on genotype were examined. The genes CYP2C8 and PPARG are the most extensively studied to date and selected polymorphisms contribute to respective variability in pioglitazone pharmacokinetics and pharmacodynamics. We hypothesized that genetic variation in pioglitazone pathway genes contributes meaningfully to the clinically observed variability in drug response. To test the hypothesis that genetic variation in PPARG associates with variability in pioglitazone response, we conducted a meta-analysis to synthesize the currently available data on the PPARG p.Pro12Ala polymorphism. The results showed that PPARG 12Ala carriers had a more favorable change in fasting blood glucose from baseline as compared to patients with the wild-type Pro12Pro genotype (p=0.018. Unfortunately, findings for many other genes lack replication in independent cohorts to confirm association; further studies are needed. Also, the biological functionality of these polymorphisms is unknown. Based on current evidence, we propose that pharmacogenomics may provide an important tool to individualize pioglitazone therapy and better optimize therapy in patients with T2DM or other conditions for which pioglitazone

  16. Pioglitazone and cancer: angel or demon?

    Science.gov (United States)

    Kostapanos, Michael S; Elisaf, Moses S; Mikhailidis, Dimitri P

    2013-01-01

    After the withdrawal of troglitazone and rosiglitazone, pioglitazone remains the sole thiazolidinedione (TZD) still available. Pioglitazone is efficacious in improving glycemic control and reduce the risk of cardiovascular events. Although generally well-tolerated, pioglitazone was withdrawn by some national medicines agencies (e.g. in France and Germany) due to reports of increased incidence of bladder cancer. In this article, we review the literature on the association between pioglitazone and cancer in several sites, including the bladder. Pioglitazone, like other TZDs, increased differentiation, inhibited growth and proliferation, while provoked apoptosis in various cancer cells, including bladder cancer, in vitro and in vivo. However, a rat-specific carcinogenic effect of pioglitazone on the bladder was noted in vivo. Clinical data for the risk of various cancer sites mostly come from observational studies and are subject to bias. An increased risk for bladder cancer by pioglitazone was suggested by retrospective analyses. This risk was associated with the time of exposure and the age, by identifying 24 months and 65 years, respectively, as time 'thresholds' above which this risk becomes relevant. In contrast, no increased risk for bladder cancer was associated with pioglitazone in randomized clinical trials. Pioglitazone was associated with increased incidence of melanoma and non-Hodgkin lymphoma and decreased risk of renal cancer in one cohort study. These findings need to be re-evaluated on a prospective basis. There is no convincing evidence that pioglitazone increases or decreases the risk of cancer in other sites. In contrast, it was suggested that this drug may be useful either in the treatment of cancer complications or as an adjunct to chemotherapeutic agents. Considering the clinical benefit from the use of pioglitazone it is reasonable to wait until data from ongoing clinical trials are available before reaching definitive conclusions. Nevertheless

  17. COMPARISON OF METFORMIN AND PIOGLITAZONE IN PCOS

    Directory of Open Access Journals (Sweden)

    Archana V.

    2013-04-01

    Full Text Available ABSTRACT: OBJECTIVES: To compare and evaluate the effects of metformin and pioglitazone on insulin resistance, ovulation and hyperandrogenis m in women with PCOS. METHODS: Total 180 patients were included in this double blind cont rolled trial between 18 to 30 years. These women were randomly allocated in two groups. After t aking written consent they were treated with either metformin or pioglitazone for 6 months a nd pretreatment versus post treatment clinical and biochemical variables were analysed an d compared. RESULTS: After treatment with metformin and pioglitazone around 50- 55 % women in both group achieved menstrual cycle regularity , and ovulation was restored in 44 % and 55 % in patients on metformin and pioglitazone respectively. Both group showed decline i n F-G score. Decrease in serum cholesterol was seen in both groups , but was more pr onounced with pioglitazone. Effect on insulin resistance and hyperinsulinemia was assessed by measuring pre and post treatment fasting serum insulin levels . Fall in serum insuli n level was more with pioglitazone and 48 % women became normoinsulinemic after treatment with pioglitazone as compared to 12 % with metformin. Rise in serum SHBG and fall in LH level was more remarkable with pioglitazone (p value < 0.05.

  18. Collateral Intimate Partner Homicide

    OpenAIRE

    Emily Meyer; Lori Post

    2013-01-01

    Collateral intimate partner homicide (CIPH) is an underinvestigated genre of intimate partner violence (IPV) where an individual(s) connected to the IPV victim is murdered. We conducted a content analysis of a statewide database of CIPH newspaper articles (1990-2007). Out of 111 collateral murder victims, there were 84 IPV female focal victims and 84 male perpetrators. The most frequently reported CIPH decedent was the...

  19. Usage of pioglitazone at Medanta, the Medicity

    Directory of Open Access Journals (Sweden)

    Ambrish Mithal

    2014-01-01

    Full Text Available Pioglitazone improves glycemic control by acting as an insulin sensitizer and is used in the management of Type 2 diabetes mellitus. Pioglitazone has recently been at the center of a controversy with regards to its safety. There is no clear consensus on how, when and in what dose the drug should be used in the management of diabetes. We have summarized our strategy on pioglitazone use in Type 2 diabetes in a large private tertiary care center - Medanta, the Medicity- which may help in generating further thought about positioning of this anti-diabetic molecule. We use pioglitazone as the fourth in the pecking order of oral anti-diabetic agents. We typically use pioglitazone in a dose of 15 mg/day. We avoid using pioglitazone with insulin. We do not use pioglitazone under following situations: In the presence of significant or proven cardiac disease, in patients who are struggling with their weight or need to lose weight, in patients at high risk for osteoporotic fractures, in patients with macular edema, in patients with pre-existing bladder cancer and would discontinue in case hematuria or any other symptom of bladder cancer develops. We continue to use the drug in patients well controlled on it without any evident side-effects or contraindications.

  20. Usage of pioglitazone at Medanta, the Medicity.

    Science.gov (United States)

    Mithal, Ambrish; Kaur, Parjeet; Bansal, Beena; Mishra, Sunil Kumar; Wasir, Jasjeet S; Jevalikar, Ganesh; Mahendru, Shama

    2014-01-01

    Pioglitazone improves glycemic control by acting as an insulin sensitizer and is used in the management of Type 2 diabetes mellitus. Pioglitazone has recently been at the center of a controversy with regards to its safety. There is no clear consensus on how, when and in what dose the drug should be used in the management of diabetes. We have summarized our strategy on pioglitazone use in Type 2 diabetes in a large private tertiary care center - Medanta, the Medicity- which may help in generating further thought about positioning of this anti-diabetic molecule. We use pioglitazone as the fourth in the pecking order of oral anti-diabetic agents. We typically use pioglitazone in a dose of 15 mg/day. We avoid using pioglitazone with insulin. We do not use pioglitazone under following situations: In the presence of significant or proven cardiac disease, in patients who are struggling with their weight or need to lose weight, in patients at high risk for osteoporotic fractures, in patients with macular edema, in patients with pre-existing bladder cancer and would discontinue in case hematuria or any other symptom of bladder cancer develops. We continue to use the drug in patients well controlled on it without any evident side-effects or contraindications.

  1. Administration of pioglitazone alone or with alogliptin delays diabetes onset in UCD-T2DM rats.

    Science.gov (United States)

    Cummings, Bethany P; Bettaieb, Ahmed; Graham, James L; Stanhope, Kimber; Haj, Fawaz G; Havel, Peter J

    2014-04-01

    There is a need to identify strategies for type 2 diabetes prevention. Therefore, we investigated the efficacy of pioglitazone and alogliptin alone and in combination to prevent type 2 diabetes onset in UCD-T2DM rats, a model of polygenic obese type 2 diabetes. At 2 months of age, rats were divided into four groups: control, alogliptin (20 mg/kg per day), pioglitazone (2.5 mg/kg per day), and alogliptin+pioglitazone. Non-fasting blood glucose was measured weekly to determine diabetes onset. Pioglitazone alone and in combination with alogliptin lead to a 5-month delay in diabetes onset despite promoting increased food intake and body weight (BW). Alogliptin alone did not delay diabetes onset or affect food intake or BW relative to controls. Fasting plasma glucose, insulin, and lipid concentrations were lower and adiponectin concentrations were threefold higher in groups treated with pioglitazone. All treatment groups demonstrated improvements in glucose tolerance and insulin secretion during an oral glucose tolerance test with an additive improvement observed with alogliptin+pioglitazone. Islet histology revealed an improvement of islet morphology in all treatment groups compared with control. Pioglitazone treatment also resulted in increased expression of markers of mitochondrial biogenesis in brown adipose tissue and white adipose tissue, with mild elevations observed in animals treated with alogliptin alone. Pioglitazone markedly delays the onset of type 2 diabetes in UCD-T2DM rats through improvements of glucose tolerance, insulin sensitivity, islet function, and markers of adipose mitochondrial biogenesis; however, addition of alogliptin at a dose of 20 mg/kg per day to pioglitazone treatment does not enhance the prevention/delay of diabetes onset.

  2. Loan collaterals and collateral substitutes in rural finance: a review ...

    African Journals Online (AJOL)

    Loan collaterals and collateral substitutes in rural finance: a review. ... Subscription or Fee Access ... Poor farm households and other microentrepreneurs have difficulties in obtaining loans from banks and other financial institutions because ... of non-traditional methods of loan security referred to as collateral substitutes.

  3. Collateral Intimate Partner Homicide

    Directory of Open Access Journals (Sweden)

    Emily Meyer

    2013-04-01

    Full Text Available Collateral intimate partner homicide (CIPH is an underinvestigated genre of intimate partner violence (IPV where an individual(s connected to the IPV victim is murdered. We conducted a content analysis of a statewide database of CIPH newspaper articles (1990-2007. Out of 111 collateral murder victims, there were 84 IPV female focal victims and 84 male perpetrators. The most frequently reported CIPH decedent was the focal victim’s new partner (30%; 45% of focal victims were themselves killed. News reports framed CIPH as the unexpected result of interpersonal conflict, despite evidence of a systematic pattern of coercion and violence that capitulated in murder.

  4. Effects of pioglitazone in familial combined hyperlipidaemia.

    NARCIS (Netherlands)

    Abbink-Zandbergen, E.J.; Graaf, J. de; Haan, J.H.A. de; Heerschap, A.; Stalenhoef, A.F.H.; Tack, C.J.J.

    2006-01-01

    OBJECTIVES: Familial combined hyperlipidaemia (FCH) is associated with insulin resistance. We hypothesized that pioglitazone treatment of FCH patients might increase insulin sensitivity, but may also improve serum lipid levels, body fat distribution, intramyocellular lipids (IMCL) and endothelial fu

  5. Effect of raw Radix Rehmanniae on the pharmacokinetics of pioglitazone in rats.

    Science.gov (United States)

    Shi, Zhan; Gao, Jingwen; Yuan, Yuemei; Zhu, Shuzhen; Yao, Meicun

    2014-05-01

    Raw Radix Rehmanniae (RRR) is a frequently used traditional Chinese medicine in the treatment of diabetes mellitus according to the statistics on all of the anti-diabetic formulas recorded in New National Traditional Chinese Medicine. Pioglitazone and RRR may be co-administrated for presumably enhanced therapeutic effects because of the common indications. Therefore, the aim of the study was to evaluate the effect of RRR on the pharmacokinetics of pioglitazone in healthy rats and type 2 diabetic rats. The pharmacokinetic effect of RRR on pioglitazone was studied in healthy rats and type 2 diabetic rats. A validated UPLC-MS/MS method was used to analyze the concentration of pioglitazone in blood samples. The pharmacokinetic parameters were calculated using non-compartmental analyses by Winnonlin 5.0.1. In healthy group, the pre-treatment of RRR significantly (Ppioglitazone; whereas in T2DM group, significant increase of C(max) and decrease of V/F and T½ were found after the rats were pre-treated with RRR. However, AUC(0-t) and CL/F remained unchanged in both healthy group and T2DM group. In conclusion, co-administration with RRR could alter the pharmacokinetic profiles of pioglitazone to statistically significant levels.

  6. Relevant incidental findings at abdominal multi-detector contrast-enhanced computed tomography:A collateral screening?

    Institute of Scientific and Technical Information of China (English)

    Luca; Maria; Sconfienza; Giovanni; Mauri; Claudia; Muzzupappa; Alessandro; Poloni; Michele; Bandirali; Anastassia; Esseridou; Stefania; Tritella; Francesco; Secchi; Giovanni; Di; Leo; Francesco; Sardanelli

    2015-01-01

    AIM: To investigate the prevalence of relevant incidental findings(RIFs) detected during routine abdominal contrast-enhanced computed tomography(Ce CT).METHODS: We retrospectively evaluated the reports of a consecutive series of abdominal Ce CT studies performed between January and May 2013. For each report, patients’ age and sex, admission as inpatient or outpatient, clinical suspicion as indicated by the requesting physician, availability of a previous abdominal examination, and name of the reporting radiologist were recorded. Based on the clinical suspicion, the presence and features of any RIFs(if needing additional workup) was noted.RESULTS: One thousand forty abdominal Ce CT were performed in 949 patients(528 males, mean age 66 ±14 years). No significant difference was found between inpatients and outpatients age and sex distribution(P > 0.472). RIFs were found in 195/1040(18.8%) Ce CT [inpatients = 108/470(23.0%); outpatients = 87/570(15.2%); P = 0.002]. RIFs were found in 30/440(6.8%) Ce CT with a previous exam and in 165/600(27.5%) without a previous exam(P < 0.001). Radiologists’ distribution between inpatients or outpatients was significantly different(P < 0.001). RIFs prevalence increased with aging, except for a peak in 40-49 year group. Most involved organs were kidneys, gallbladder, and lungs.CONCLUSION: A RIF is detected in 1/5 patients undergoing abdominal Ce CT. Risk of overdiagnosis should be taken into account.

  7. The relationship of serum erythropoietin level with coronary collateral grade.

    Science.gov (United States)

    Sahinarslan, Asife; Yalcin, Ridvan; Kocaman, Sinan Altan; Ercin, Ugur; Tanalp, Ali Cevat; Topal, Salih; Bukan, Neslihan; Boyaci, Bulent; Cengel, Atiye

    2011-01-01

    Erythropoietin has been shown to induce neovascularization and protect against ischemic vascular injury. We investigated whether a higher serum erythropoietin (EPO) level is related to better coronary collateral vessel grade. Ninety-nine patients with stable angina pectoris who have at least 1 coronary stenosis of equal to or greater than 70% at coronary angiography were prospectively enrolled. Serum EPO and vascular endothelial growth factor (VEGF) levels were studied. Coronary collateral degree was graded according to the Rentrop method. Patients with grade 2-3 collateral degree were included in the good collateral group and formed Group I. The patients with grade 0-1 collateral degree were included in the poor collateral group and formed Group II. The serum EPO level was significantly higher in the good collateral group (17.3 ± 9.3 mU/mL vs 11.7 ± 5.0 mU/mL; P < 0.001). There was also a positive correlation between serum EPO level and Rentrop score (r = 0.39; P < 0.001). In multivariate analysis, serum EPO level (odds ratio [OR] 1.336; 95% confidence interval [CI], 1.120-1.593; P = 0.001), oxygen saturation (OR 0.638; 95% CI, 0.422-0.963; P = 0.033) and presence of chronic total occlusion (CTO) (OR 26.7; 95% CI, 3.874-184.6; P = 0.001) were independently related to well-developed coronary collaterals. Higher serum EPO level is related to better coronary collateral development. Erythropoietin may have a positive effect on the development of collaterals and may provide a new agent for the treatment strategies to enhance coronary collateral vessel development. Copyright © 2011 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  8. Pioglitazone

    Science.gov (United States)

    ... following: atorvastatin (Lipitor, in Caduet), gemfibrozil (Lopid), hormonal contraceptives (birth control pills, patches, rings, implants, and injections), insulin or other medications to treat ...

  9. Pioglitazone in adult rats reverses immediate postnatal overfeeding-induced metabolic, hormonal, and inflammatory alterations.

    Science.gov (United States)

    Boullu-Ciocca, S; Tassistro, V; Dutour, A; Grino, M

    2015-12-01

    Immediate postnatal overfeeding in rats, obtained by reducing the litter size, results in early-onset obesity. Such experimental paradigm programs overweight, insulin resistance, dyslipidemia, increased adipose glucocorticoid metabolism [up-regulation of glucocorticoid receptor (GR) and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)], and overexpression of proinflammatory cytokines in mesenteric adipose tissue (MAT) in adulthood. We studied the effects of pioglitazone, a PPARγ agonist, treatment on the above-mentioned overfeeding-induced alterations. Nine-month-old rats normofed or overfed during the immediate postnatal period were given pioglitazone (3 mg/kg/day) for 6 weeks. Pioglitazone stimulated weight gain and induced a redistribution of adipose tissue toward epididymal location with enhanced plasma adiponectin. Treatment normalized postnatal overfeeding-induced metabolic alterations (increased fasting insulinemia and free fatty acids) and mesenteric overexpression of GR, 11β-HSD11, CD 68, and proinflammatory cytokines mRNAs, including plasminogen-activator inhibitor type 1. Mesenteric GR mRNA levels correlated positively with mesenteric proinflammatory cytokines mRNA concentrations. In vitro incubation of MAT obtained from overfed rats demonstrated that pioglitazone induced a down-regulation of GR gene expression and normalized glucocorticoid-induced stimulation of 11β-HSD1 and plasminogen-activator inhibitor type 1 mRNAs. Our data show for the first time that the metabolic, endocrine, and inflammatory alterations induced by early-onset postnatal obesity can be reversed by pioglitazone at the adulthood. They demonstrate that pioglitazone, in addition to its well-established effect on adipose tissue redistribution and adiponectin secretion, reverses programing-induced adipose GR, 11β-HSD1, and proinflammatory cytokines overexpression, possibly through a GR-dependent mechanism.

  10. Effect of pioglitazone treatment in a patient with secondary multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Pershadsingh Harrihar A

    2004-04-01

    Full Text Available Abstract Background Ligands of the peroxisome proliferator-activated receptor-gamma (PPARγ induce apoptosis in activated T-lymphocytes and exert anti-inflammatory effects in glial cells. Preclinical studies have shown that the thiazolidinedione pioglitazone, an FDA-approved PPARγ agonist used to treat type 2 diabetes, delays the onset and reduces the severity of clinical symptoms in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS. We therefore tested the safety and therapeutic potential of oral pioglitazone in a patient with secondary MS. Case presentation The rationale and risks of taking pioglitazone were carefully explained to the patient, consent was obtained, and treatment was initiated at 15 mg per day p.o. and then increased by 15 mg biweekly to 45 mg per day p.o. for the duration of the treatment. Safety was assessed by measurements of metabolic profiles, blood pressure, and edema; effects on clinical symptoms were assessed by measurement of cognition, motor function and strength, and MRI. Within 4 weeks the patient exhibited increased appetite, cognition and attention span. After 12 months treatment, body weight increased from 27.3 to 35.9 kg (32% and maintained throughout the duration of the study. Upper extremity strength and coordination improved, and increased fine coordination was noted unilaterally after 8 months and bilaterally after 15 months. After 8 months therapy, the patient demonstrated improvement in orientation, short-term memory, and attention span. MRIs carried out after 10 and 18 months of treatment showed no perceptible change in overall brain atrophy, extent of demyelination, or in Gd-enhancement. After 3.0 years on pioglitazone, the patient continues to be clinically stable, with no adverse events. Conclusions In a patient with secondary progressive MS, daily treatment with 45 mg p.o. pioglitazone for 3 years induced apparent clinical improvement without adverse events

  11. Cardioprotective effect of pioglitazone in diabetic and non-diabetic rats subjected to acute myocardial infarction involves suppression of AGE-RAGE axis and inhibition of apoptosis.

    Science.gov (United States)

    Khodeer, Dina M; Zaitone, Sawsan A; Farag, Noha E; Moustafa, Yasser M

    2016-05-01

    Insulin resistance increases risk of cardiovascular diseases. This work investigated the protective effect of pioglitazone on myocardial infarction (MI) in non-diabetic and diabetic rats, focusing on its role on advanced glycated endproducts (AGEs) and cardiac apoptotic machinery. Male rats were divided into 2 experiments: experiment I and II (non-diabetic and diabetic rats) were assigned as saline, MI (isoproterenol, 85 mg/kg, daily), and MI+pioglitazone (5, 10, and 20 mg/kg). Injection of isoproterenol in diabetic rats produced greater ECG disturbances compared to non-diabetic rats. Treatment with pioglitazone (5 mg/kg) reduced the infarct size and improved some ECG findings. Pioglitazone (10 mg/kg) enhanced ECG findings, improved the histopathological picture and downregulated apoptosis in cardiac tissues. Whereas the higher dose of pioglitazone (20 mg/kg) did not improve most of the measured parameters but rather worsened some of them, such as proapoptotic markers. Importantly, a positive correlation was found between serum AGEs and cardiac AGE receptors (RAGEs) versus caspase 3 expression in the two experiments. Therefore, the current effect of pioglitazone was, at least in part, mediated through downregulation of AGE-RAGE axis and inhibition of apoptosis. Consequently, these data suggest that pioglitazone, at optimized doses, may have utility in protection from acute MI.

  12. Pioglitazone:A review of analytical methods

    Institute of Scientific and Technical Information of China (English)

    N. Satheeshkumar; S. Shantikumar; R. Srinivas

    2014-01-01

    Pioglitazone is an oral anti-hyperglycemic agent. It is used for the treatment of diabetes mellitus type 2. It selectively stimulates nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-gamma). It was the tenth-best-selling drug in the U.S. in 2008. This article examines published analytical methods reported so far in the literature for the determination of pioglitazone in biological samples and pharmaceutical formulations. They include various techniques like electrochemical methods, spectrophotometry, capillary electrophoresis, high-performance liquid chromatography, liquid chromatography-electrospray ionization-tandem mass spectrometry and high-performance thin layer chromatography.

  13. Collateralized debt obligations (CDOs

    Directory of Open Access Journals (Sweden)

    Dragosavac Miloš

    2012-01-01

    Full Text Available Collateralized debt obligations (CDOs were issued in 1987 by bankers at Drexel Burnham Lambert Inc. A decade later, CDOs became the leading power on the credit derivative markets, on which the value of derivative assets was derived from the value of other assets. However, unlike options and credit swamps, CDOs are not real, which means that they are constructed, and sometimes even the construction of their construction. CDOs were made to satisfy different types of investors, at one end, there is low-risk with low-income, and at the other, high-risk with high-income. By 2007, following the bubble burst on the US real estate market, losses on the CDO market started to expand. By 2008, the crisis on the CDO market turned into what we call today 'the global financial crisis.' CDOs are 'in the heart' of the crisis, and even wider. Our attempt is to reveal the mechanism of collateralized debt obligations (CDOs and the way in which CDOs expanded the negative effects of the present global financial crisis.

  14. Impaired insulin activation and dephosphorylation of glycogen synthase in skeletal muscle of women with polycystic ovary syndrome is reversed by pioglitazone treatment

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Højlund, Kurt; Andersen, Nicoline Resen

    2008-01-01

    . No significant abnormalities in GSK-3alpha or -3beta were found in PCOS subjects. Pioglitazone treatment improved insulin-stimulated glucose metabolism and GS activity in PCOS (all P ... of GS including absent dephosphorylation at sites 2+2a contributes to insulin resistance in skeletal muscle in PCOS. The ability of pioglitazone to enhance insulin sensitivity, in part, involves improved insulin action on GS activity and dephosphorylation at NH2-terminal sites....

  15. Pioglitazone-induced Pulmonary Injury in a Very Elderly Patient.

    Science.gov (United States)

    Katayama, Kohta; Kumagai, Ryo; Isono, Momoko; Fujihara, Kazuya; Yagyu, Hiroaki; Ohara, Gen; Kagohashi, Katsunori; Satoh, Hiroaki

    2016-01-01

    An 85-year-old woman with diabetes mellitus was admitted to our hospital due to progressive dyspnea. Two months previously, pioglitazone had been newly prescribed for diabetes management. Bilateral ground-glass opacities and progressive respiratory deterioration suggested respiratory failure due to a drug-induced lung injury. With discontinuation of pioglitazone and the administration of a corticosteroid, an improvement in her respiratory condition was achieved, although sequelae remained in some areas of the lungs. Results of drug-induced lymphocyte stimulation tests were positive for pioglitazone. Resumption of other drugs did not reinduce the lung injury. Therefore, a diagnosis of pioglitazone-induced lung injury was made. Although pioglitazone-induced lung injury is very rare, clinicians should keep it in mind when pioglitazone is used.

  16. Pioglitazone suppresses advanced glycation end product-induced expression of plasminogen activator inhibitor-1 in vascular smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    Xiaochen Yuan; Naifeng Liu

    2011-01-01

    Advanced glycation end products (AGEs) play an important role in vascular complications of diabetes, including fibrinolytic abnormalities.Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARΥ) agonist, has recently been shown to reduce circulating plasminogen activator inhibitor-1 (PAI-1) levels in diabetes mellitus. In the present study, we investigated the effects of pioglitazone on the expression of local PAI-1 in rat vascular smooth muscle cells (VSMCs) induced by AGEs and the underlying mechanism. The result showed that AGEs could enhance the PAI-1 expression by 5.1-fold in mRNA and 2.7-fold in protein level, as evaluated by real-time RT-PCR and Western blotting,respectively. Pioglitazone was found to down-regulate the AGE-stimulated PAI-1 expression in VSMCs. However, these inhibitory effects were partially attenuated by the PPARΥ antagonist, GW9662. Furthermore, we found that AGEs induced a rapid increase in phosphorylation and activation of extracellular signal-regulated protein kinase 1/2 (ERK 1/2). The ERK kinase inhibitor, UO126, partially prevented the induction of PAI-1 by AGEs. Moreover, pioglitazone was also found to inhibit the phosphorylation of ERKi/2. Taken together, it was concluded that pioglitazone could inhibit AGE-induced PAI-1 expression, which was mediated by the ERK1/2 and PPARΥ pathways. Our findings suggestedpioglitazone had a therapeutic potential in improving fibrinolytic activity, and consequently preventing thromboembolic complications of diabetes and cardiovascular disease.

  17. Pioglitazone attenuates cardiac fibrosis and hypertrophy in a rat model of diabetic nephropathy.

    Science.gov (United States)

    Elrashidy, Rania A; Asker, Mervat E; Mohamed, Hoda E

    2012-09-01

    Pioglitazone has been demonstrated to have beneficial effects on cardiovascular outcomes. However, little is known about its effect on cardiac remodeling associated with diabetic nephropathy. Therefore, this study was designed to study the effects of pioglitazone on cardiac fibrosis and hypertrophy in a rat model of diabetic nephropathy. For this purpose, male Wistar albino rats were randomly assigned into 4 groups (n = 10 per group): normal (N) group, diabetic (D) group, diabetic nephropathic (DN) group received an equal amount of vehicle (0.5% carboxy methyl cellulose), and diabetic nephropathic group treated by oral administration of pioglitazone (10 mg/kg per d) for 4 weeks. Diabetic nephropathy was induced by subtotal nephrectomy plus streptozotocin (STZ) injection. The results revealed that DN rats showed excessive deposition of collagen fibers in their cardiac tissue, along with a marked myocyte hypertrophy. This was associated with a dramatic upregulation of cardiac transforming growth factor-β1 (TGF-β1) gene. Furthermore, the gene expression of matrix metalloproteinase 2 (MMP-2) decreased, while the gene expression of tissue inhibitor of metalloproteinase 2 (TIMP-2) increased in the hearts of DN rats. In addition, enhanced lipid peroxidation and myocardial injury, evidenced by a significant increase in their serum creatine kinase-MB level were observed in DN rats. All these abnormalities were ameliorated by pioglitazone administration. Our findings suggest that upregulation of cardiac TGF-β1 gene along with the imbalance between MMP-2 and TIMP-2 expressions is critically involved in cardiac fibrosis associated with diabetic nephropathy. Pioglitazone can ameliorate cardiac remodeling by suppressing the gene expression of TGF-β1 and regulating the MMP-2/TIMP-2 system.

  18. Taurine and pioglitazone attenuate diabetes-induced testicular damage by abrogation of oxidative stress and up-regulation of the pituitary-gonadal axis.

    Science.gov (United States)

    Abd El-Twab, Sanaa M; Mohamed, Hanaa M; Mahmoud, Ayman M

    2016-06-01

    Chronic hyperglycemia is associated with impairment of testicular function. The current study aimed to investigate the protective effects and the possible mechanisms of taurine and pioglitazone against diabetes-induced testicular dysfunction in rats. Diabetes was induced by streptozotocin injection. Both normal and diabetic rats received taurine (100 mg/kg) or pioglitazone (10 mg/kg) orally and daily for 6 weeks. Diabetic rats showed a significant (P Taurine and pioglitazone alleviated hyperglycemia, decreased pro-inflammatory cytokines, and increased circulating levels of insulin, testosterone, LH, and FSH. Gene and protein expression of LH and FSH receptors and cytochrome P450 17α-hydroxylase (CYP17) was significantly (P taurine and pioglitazone. In addition, taurine and pioglitazone significantly decreased lipid peroxidation and DNA damage, and enhanced activity of the antioxidant enzymes in testes of diabetic rats. In conclusion, taurine and pioglitazone exerted protective effects against diabetes-induced testicular damage through attenuation of hyperglycemia, inflammation, oxidative stress and DNA damage, and up-regulation of the pituitary/gonadal axis.

  19. Pioglitazone, a specific ligand of peroxisome proliferator-activated receptor-gamma, protects pancreas against acute cerulein-induced pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Peter C Konturek; Artur Dembinski; Zygmunt Warzecha; Grzegorz Burnat; Piotr Ceranowicz; Eckhart G Hahn; Marcin Dembinski; Romana Tomaszewska; Stanislaw J Konturek

    2005-01-01

    AIM: To determine the effect of pioglitazone, a specific peroxisome proliferator-activated receptor-γ (PPARγ)ligand, on the development of acute pancreatitis (AP) and on the expression of heat shock protein 70 (HSP70) in the pancreas.METHODS: AP was induced in rats by subcutaneous infusion of cerulein for 5 h. Pancreatic blood flow was measured by laser Doppler flowmetry. Plasma lipase activity, interleukin-1β (IL-1β) and IL-10 were determined.Pancreatic weight and histology were evaluated and pancreatic DNA synthesis and blood flow as well as pancreatic mRNA for IL-1β and HSP70 were assessed in rats treated with pioglitazone alone or in combination with cerulein.RESULTS: Pioglitazone administered (10-100 mg/kg I.g.)30 min before cerulein, attenuated dose-dependently the pancreatic tissue damage in cerulein-induced pancreatitis (CIP) as demonstrated by the improvement of pancreatic histology, reduction in plasma lipase activity,plasma concentration of pro-inflammatory IL-1β and its gene expression in the pancreas and attenuation of the pancreatitis-evoked fall in pancreatic blood flow. CIP increased pancreatic HSP70 mRNA and protein expression in the pancreas and this effect was enhanced by pioglitazone treatment.CONCLUSION: Pioglitazone attenuates CIP and the beneficial effect of this pioglitazone is multifactorial probably due to its anti-inflammatory activities, to the suppression of IL-1β and to the overexpression of HSP70.PPARγ ligands could represent a new therapeutic option in the treatment of AP.

  20. Pioglitazone, a specific ligand of peroxisome proliferator-activated receptor-gamma, protects pancreas against acute cerulein-induced pancreatitis

    Science.gov (United States)

    Konturek, Peter C; Dembinski, Artur; Warzecha, Zygmunt; Burnat, Grzegorz; Ceranowicz, Piotr; Hahn, Eckhart G; Dembinski, Marcin; Tomaszewska, Romana; Konturek, Stanislaw J

    2005-01-01

    AIM: To determine the effect of pioglitazone, a specific peroxisome proliferator-activated receptor-γ (PPARγ) ligand, on the development of acute pancreatitis (AP) and on the expression of heat shock protein 70 (HSP70) in the pancreas. METHODS: AP was induced in rats by subcutaneous infusion of cerulein for 5 h. Pancreatic blood flow was measured by laser Doppler flowmetry. Plasma lipase activity, interleukin-1β (IL-1β) and IL-10 were determined. Pancreatic weight and histology were evaluated and pancreatic DNA synthesis and blood flow as well as pancreatic mRNA for IL-1β and HSP70 were assessed in rats treated with pioglitazone alone or in combination with cerulein. RESULTS: Pioglitazone administered (10-100 mg/kg i.g.) 30 min before cerulein, attenuated dose-dependently the pancreatic tissue damage in cerulein-induced pancreatitis (CIP) as demonstrated by the improvement of pancreatic histology, reduction in plasma lipase activity, plasma concentration of pro-inflammatory IL-1β and its gene expression in the pancreas and attenuation of the pancreatitis-evoked fall in pancreatic blood flow. CIP increased pancreatic HSP70 mRNA and protein expression in the pancreas and this effect was enhanced by pioglitazone treatment. CONCLUSION: Pioglitazone attenuates CIP and the beneficial effect of this pioglitazone is multifactorial probably due to its anti-inflammatory activities, to the suppression of IL-1β and to the overexpression of HSP70. PPARγ ligands could represent a new therapeutic option in the treatment of AP. PMID:16419161

  1. The impact of pioglitazone on bladder cancer and cardiovascular events.

    Science.gov (United States)

    Lee, Esther J; Marcy, Todd R

    2014-08-01

    Type 2 diabetes mellitus (T2DM) is a chronic condition with increasing prevalence and severe complications. Thiazolidinediones have been marketed since 1997 and are effective glucose-lowering drugs, but individual drugs within the class have been linked to serious adverse effects that resulted in the removal of troglitazone from the market, restrictions to rosiglitazone's use, and a warning added to pioglitazone's label. In 2007, a meta-analysis linked rosiglitazone to myocardial infarction (MI). Pioglitazone does not appear to share this risk. To the contrary, pioglitazone may reduce risk for MI. However, retrospective evaluations have increasingly linked pioglitazone to a higher risk of bladder cancer that appears to be time- and dose-dependent. Pioglitazone remains a medication appropriate for consideration in the management of T2DM; however, clinicians and patients should weigh its risks compared with alternatives, with a regular review of risks.

  2. Collateral sensitivity of antibiotic-resistant microbes.

    Science.gov (United States)

    Pál, Csaba; Papp, Balázs; Lázár, Viktória

    2015-07-01

    Understanding how evolution of microbial resistance towards a given antibiotic influences susceptibility to other drugs is a challenge of profound importance. By combining laboratory evolution, genome sequencing, and functional analyses, recent works have charted the map of evolutionary trade-offs between antibiotics and have explored the underlying molecular mechanisms. Strikingly, mutations that caused multidrug resistance in bacteria simultaneously enhanced sensitivity to many other unrelated drugs (collateral sensitivity). Here, we explore how this emerging research sheds new light on resistance mechanisms and the way it could be exploited for the development of alternative antimicrobial strategies.

  3. Dynamics of the Collateral Encyclopedia

    DEFF Research Database (Denmark)

    Thellefsen, Torkild Leo; Sørensen, Bent; Thellefsen, Martin Muderspach

    2015-01-01

    Both Umberto Eco and Charles S. Peirce have been concerned with the notion of background knowledge. Eco refers to background knowledge as the encyclopedia; Peirce’s term of reference is collateral experience. The aim of this article is to investigate the degree to which these two concepts...... are comparable. We focus on one major metaphysical issue, viz. the fact that Eco defines collateral experience, which is the first step in any process of cognition, as private, whereas Peirce, as a realist, would never accept the concept of private thoughts, feelings, etc. We suggest that freeing collateral...... experience from its nominalistic nomenclature makes possible a comparison and synthesis of Eco’s and Peirce’s conceptions when seen from the perspectives of their cognitive type, nuclear type, and molar content....

  4. Central bank operating frameworks and collateral markets

    OpenAIRE

    Bank for International Settlements

    2015-01-01

    Collateral markets have become increasingly important as demand for collateral assets has increased in recent years, driven by changing market practices and an evolving regulatory landscape. This report explores whether and how the design of central banks' operational frameworks influences private collateral markets, including collateral availability, pricing, related market practices, and market performance under stress. It studies these issues by reviewing available information from a range...

  5. Pioglitazone Improves Survival In Patients With Cancer: The Hypothesis

    Directory of Open Access Journals (Sweden)

    Banshi Saboo

    2015-12-01

    Full Text Available Pioglitazone is currently the only thiazolidinedione approved by regulatory agencies worldwide for the treatment of type 2 diabetes mellitus (T2DM. The use of pioglitazone in patients with T2DM has been limited because earlier studies showed moderate weight gain and an increased incidence of heart failure, osteoporotic fractures, and bladder cancer. However, new studies have shown that pioglitazone improves both systolic and diastolic left ventricular function and that there is no association between pioglitazone and bladder cancer. Furthermore, pioglitazone is associated with a reduced risk of all-cause mortality in patients with T2DM. Pioglitazone was also found to reduce the incidence of lung, head and neck, breast, colorectal, and hepatocellular cancer. There is tremendous preclinical evidence that links thiazolidinediones with anti-cancer effects. Three possible mechanisms of anti-proliferative effects induced by peroxisome proliferator activated receptor gamma (PPARG agonists emerge: 1 activation of PPARG and epidermal growth factor receptor, which actives several intracellular pathways involved in carcinogenesis; 2 increase in serum adiponectin levels and decrease in serum leptin levels, which are associated with lower cancer risk and more favorable outcomes in patients with cancer; 3 modulate insulin-like growth factor 1 (IGF-1 receptor signaling by decreasing IGF-1 levels and increasing the expression of IGF binding protein 1. To date, there are no prospective, placebo-controlled trials that have analyzed the efficacy of pioglitazone in chemotherapy and chemoprevention. Only one ongoing study has shown that pioglitazone has an excellent capability of eradicating quiescent leukemia stem cells in patients with chronic myeloid leukemia and achieving a complete molecular response. Current evidence supports our theory that future case-control studies examining pioglitazone as chemotherapy, or adjuvant chemotherapy, should be performed in

  6. Expression of REST4 in human gliomas in vivo and influence of pioglitazone on REST in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Huan [Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008 (China); Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078 (China); Gao, Zhangfeng [Department of Neurosurgery, Second Xiangya Hospital of Central South University, Changsha 410008 (China); Wu, Nayiyuan; Zeng, Liu; Tang, Xinyue; Chen, Xiaoping; Liu, Zhaoqian; Zhang, Wei; Wang, Liansheng [Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008 (China); Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078 (China); Li, Zhi, E-mail: lizhi489@163.com [Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008 (China); Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078 (China)

    2015-08-07

    The repressor element-1 (RE1) silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) has an irreplaceable role during the differentiation of neurons. REST has multiple splice variants which link to various types of cancer. Previous work had highlighted the role of REST in glioma, where the expression of REST is enhanced. But whether alternative splicing of REST is expressed in glioma has not been described. Here, we show that a specific isoform REST4 is expressed in glioma specimens, and will influence the mRNA level of REST in vivo. Peroxisome proliferator-activated receptor-γ (PPARγ) agonists have a role of antineoplastic in various tumor cells, which including glioma cells. Moreover, study indicated that PPARγ agonist pioglitazone can promote alternative splicing of REST pre-mRNA. In this study, we selected pioglitazone as a tool drug to explore whether the role of pioglitazone in anti-glioma is mediated by regulating REST expression or promoting alternative splicing of REST in glioma cells. Results show that pioglitazone can inhibit proliferation and induce apoptosis of glioma cell in vitro, which may be mediated by down-regulating REST mRNA level but not by inducing alternative splicing of REST pre-mRNA. Our study firstly reports the expression of REST4 in glioma tissue samples. And we recommend that pioglitazone, which can reduce the expression level of REST, represents a promising drug for therapy of glioma. - Highlights: • A specific isoform REST4 is expressed in glioma specimens in vivo. • REST4 will influence the mRNA level of REST in vivo. • Pioglitazone can inhibit proliferation and induce apoptosis of glioma cells. • The role of pioglitazone in anti-glioma may be mediated by down-regulating REST.

  7. Anti-diabetes drug pioglitazone ameliorates synaptic defects in AD transgenic mice by inhibiting cyclin-dependent kinase5 activity.

    Directory of Open Access Journals (Sweden)

    Jinan Chen

    Full Text Available Cyclin-dependent kinase 5 (Cdk5 is a serine/threonine kinase that is activated by the neuron specific activators p35/p39 and plays many important roles in neuronal development. However, aberrant activation of Cdk5 is believed to be associated with the pathogenesis of several neurodegenerative diseases, including Alzheimer's disease (AD and Parkinson's disease (PD. Here in the present study, enhanced Cdk5 activity was observed in mouse models of AD; whereas soluble amyloid-β oligomers (Aβ, which contribute to synaptic failures during AD pathogenesis, induced Cdk5 hyperactivation in cultured hippocampal neurons. Inhibition of Cdk5 activity by pharmacological or genetic approaches reversed dendritic spine loss caused by soluble amyloid-β oligomers (Aβ treatment. Interestingly, we found that the anti-diabetes drug pioglitazone could inhibit Cdk5 activity by decreasing p35 protein level. More importantly, pioglitazone treatment corrected long-term potentiation (LTP deficit caused by Aβ exposure in cultured slices and pioglitazone administration rescued impaired LTP and spatial memory in AD mouse models. Taken together, our study describes an unanticipated role of pioglitazone in alleviating AD and reveals a potential therapeutic drug for AD curing.

  8. Effects of pioglitazone mediated activation of PPAR-γ on CIDEC and obesity related changes in mice.

    Directory of Open Access Journals (Sweden)

    Bilal Haider Shamsi

    Full Text Available OBJECTIVE: Obesity is a metabolic disorder that can lead to high blood pressure, increased blood cholesterol and triglycerides, insulin resistance, and diabetes mellitus. The aim was to study the effects of pioglitazone mediated sensitization of peroxisome proliferator-activated receptor gamma (PPAR-γ on the relationship of Cell death-inducing DFFA-like effector C (CIDEC with obesity related changes in mice. METHODS: Sixty C57B/L6 mice weighing 10-12g at 3 weeks of age were randomly divided into 3 groups. Mice in Group 1 were fed on normal diet (ND while Group 2 mice were given high fat diet (HFD, and Group 3 mice were given high fat diet and treated with Pioglitazone (HFD+P. Body weight, length and level of blood sugar were measured weekly. Quantitative real-time PCR, fluorescence microscopy, and ELISA were performed to analyze the expression of CIDEC and PPAR-γ in visceral adipose tissue (VAT and subcutaneous adipose tissue (SAT. RESULTS: Body weight and length of mice increased gradually with time in all groups. Blood sugar in HFD mice started to increase significantly from the mid of late phase of obesity while pioglitazone attenuated blood sugar level in HFD+P mice. The mRNA expressions and protein levels of PPAR-γ and CIDEC genes started to increase in HFD mice as compared to ND mice and decreased gradually during the late phase of obesity in VAT. Pioglitazone enhanced the expression of PPAR-γ and CIDEC genes in HFD+P mice even during the late phase of obesity. CONCLUSION: It is insinuated that VAT is associated with late phase obesity CIDEC decrease and insulin resistance, while pioglitazone enhances CIDEC through activation of PPAR-γ, increases its expression, and decreases lipolysis, hence preventing an increase of blood sugar in mice exposed to HFD.

  9. Understanding Collateral Evolution in Linux Device Drivers

    DEFF Research Database (Denmark)

    Padioleau, Yoann; Lawall, Julia Laetitia; Muller, Gilles

    2006-01-01

    no tools to help in this process, collateral evolution is thus time consuming and error prone.In this paper, we present a qualitative and quantitative assessment of collateral evolution in Linux device driver code. We provide a taxonomy of evolutions and collateral evolutions, and use an automated patch......-analysis tool that we have developed to measure the number of evolutions and collateral evolutions that affect device drivers between Linux versions 2.2 and 2.6. In particular, we find that from one version of Linux to the next, collateral evolutions can account for up to 35% of the lines modified in such code....

  10. Understanding Collateral Evolution in Linux Device Drivers

    DEFF Research Database (Denmark)

    Padioleau, Yoann; Lawall, Julia Laetitia; Muller, Gilles

    2006-01-01

    no tools to help in this process, collateral evolution is thus time consuming and error prone.In this paper, we present a qualitative and quantitative assessment of collateral evolution in Linux device driver code. We provide a taxonomy of evolutions and collateral evolutions, and use an automated patch......-analysis tool that we have developed to measure the number of evolutions and collateral evolutions that affect device drivers between Linux versions 2.2 and 2.6. In particular, we find that from one version of Linux to the next, collateral evolutions can account for up to 35% of the lines modified in such code....

  11. A brief etymology of the collateral circulation.

    Science.gov (United States)

    Faber, James E; Chilian, William M; Deindl, Elisabeth; van Royen, Niels; Simons, Michael

    2014-09-01

    It is well known that the protective capacity of the collateral circulation falls short in many individuals with ischemic disease of the heart, brain, and lower extremities. In the past 15 years, opportunities created by molecular and genetic tools, together with disappointing outcomes in many angiogenic trials, have led to a significant increase in the number of studies that focus on: understanding the basic biology of the collateral circulation; identifying the mechanisms that limit the collateral circulation's capacity in many individuals; devising methods to measure collateral extent, which has been found to vary widely among individuals; and developing treatments to increase collateral blood flow in obstructive disease. Unfortunately, accompanying this increase in reports has been a proliferation of vague terms used to describe the disposition and behavior of this unique circulation, as well as the increasing misuse of well-ensconced ones by new (and old) students of collateral circulation. With this in mind, we provide a brief glossary of readily understandable terms to denote the formation, adaptive growth, and maladaptive rarefaction of collateral circulation. We also propose terminology for several newly discovered processes that occur in the collateral circulation. Finally, we include terms used to describe vessels that are sometimes confused with collaterals, as well as terms describing processes active in the general arterial-venous circulation when ischemic conditions engage the collateral circulation. We hope this brief review will help unify the terminology used in collateral research.

  12. Breast varices: imaging findings of an unusual presentation of collateral pathways in superior vena caval syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Oezdemir, Ayseguel E-mail: aozdemir@tip.gazi.edu.tr; Ilgit, Erhan T.; Konus, Oeznur L.; Cetin, Meltem; Oezsunar, Yelda

    2000-11-01

    Imaging findings are presented of an unusual pathway of collateral circulation consisting of bilateral and diffuse dilated breast veins from a patient with long standing superior vena caval syndrome. The main importance of this case is the extent of the collateral development through the breast veins, serving as the major pathway of collateral circulation. Identification of this unusual collateral development, which resembles breast varices, was performed with contrast-enhanced chest CT scans, digital subtraction venography, color Doppler ultrasonography, and mammographic studies. Collateral development was secondary to a long segment idiopathic venous occlusion involving bilateral subclavian and brachiocephalic veins as well as vena cava superior. We conclude that dilated breast veins when detected on any imaging modality should raise the suspicion of central venous obstruction.

  13. An experimental study of pioglitazone in treating vascular dementia

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To compare the therapeutic effects of different doses of pioglitazone,a kind of peroxisome proliferator-activated receptor γ(PPARγ)agonist,on vascular dementia and explore how pioglitazone affects cerebral ischemia.Methods Modified Pulsinelli's vessel ligation was used to establish a vascular dementia model in rats.Recognition,learning and memory were evaluated by Morris's water maze test.Immunoenzyme staining was used to determine the number of nerve cells.Immunofluorescence double-staining was u...

  14. Pioglitazone use and the risk of bladder cancer.

    Science.gov (United States)

    Kuo, Hsin-Wei; Tiao, Mao-Meng; Ho, Shu-Chen; Yang, Chun-Yuh

    2014-02-01

    This study aimed to identify the risk association between pioglitazone exposure and bladder cancer. A nested case-control study was performed using a representative database randomly sampled from National Health Insurance enrollees. The source cohort consisted of newly diagnosed diabetic patients from 1997 to 2009. Cases were identified as those with a diagnosis of bladder cancer from 2002 to 2009. For each case, four matched control individuals were randomly selected. A multiple logistic regression model was used to estimate the relative magnitude of risk in relation to the use of pioglitazone. In total, 259 cases and 1036 controls were identified. The prevalent use of pioglitazone is similar in cases and controls (adjusted odds ratio, 1.20; 95% confidence interval, 0.58-2.49). Compared to nonusers, these values were 1.08 (0.41-2.88) for those with cumulative pioglitazone use ≤ 8268 mg and 1.35 (0.48-3.79) for those with cumulative pioglitazone use > 8268 mg. This study does not provide support for the risk association between pioglitazone exposure and bladder cancer. Further confirmation is needed due to the limitation of small case number with relatively shorter exposure duration and lower cumulative dose.

  15. Pioglitazone, a PPARγ agonist, provides comparable protection to angiotensin converting enzyme inhibitor ramipril against adriamycin nephropathy in rat.

    Science.gov (United States)

    Ochodnicky, Peter; Mesarosova, Lucia; Cernecka, Hana; Klimas, Jan; Krenek, Peter; Goris, Maaike; van Dokkum, Richard P E; Henning, Robert H; Kyselovic, Jan

    2014-05-05

    Peroxisome proliferator-activated receptor γ (PPARγ) agonists have been shown to ameliorate diabetic nephropathy, but much less are known about their effects in non-diabetic nephropathies. In the present study, metabolic parameters, blood pressure, aortic endothelial function along with molecular and structural markers of glomerular and tubulointerstitial renal damage, were studied in a rat model of normotensive nephropathy induced by adriamycin and treated with PPARγ agonist pioglitazone (12mg/kg, po), angiotensin converting enzyme (ACE) inhibitor ramipril (1mg/kg, po) or their combination. Pioglitazone had no effect on systolic blood pressure, marginally reduced glycemia and improved aortic endothelium-dependent relaxation. In the kidney, pioglitazone prevented the development of proteinuria and focal glomerulosclerosis to the similar extent as blood-pressure lowering ramipril. Renoprotection provided by either treatment was associated with a reduction in the cortical expression of profibrotic plasminogen activator inhibitor-1 and microvascular damage-inducing endothelin-1, and a limitation of interstitial macrophage influx. Treatment with PPARγ agonist, as well as ACE inhibitor comparably affected renal expression of the renin-angiotensin system (RAS) components, normalizing increased renal expression of ACE and enhancing the expression of Mas receptor. Interestingly, combined pioglitazone and ramipril treatment did not provide any additional renoprotection. These results demonstrate that in a nondiabetic renal disease, such as adriamycin-induced nephropathy, PPARγ agonist pioglitazone provides renoprotection to a similar extent as an ACE inhibitor by interfering with the expression of local RAS components and attenuating related profibrotic and inflammatory mechanisms. The combination of the both agents, however, does not lead to any additional renal benefit.

  16. Differential impact of diabetes mellitus type II and arterial hypertension on collateral artery growth and concomitant macrophage accumulation.

    Science.gov (United States)

    Ito, Wulf D; Lund, Natalie; Sager, Hendrik; Becker, Wiebke; Wenzel, Ulrich

    2015-01-01

    Diabetes mellitus type II and arterial hypertension are major risk factors for peripheral arterial disease and have been considered to reduce collateral growth (arteriogenesis). Collateral growth proceeds through different stages. Vascular proliferation and macrophage accumulation are hallmarks of early collateral growth. We here compare the impact of arterial hypertension and diabetes mellitus type II on collateral proliferation (Brdu incorporation) and macrophage accumulation (ED 2 staining) as well as collateral vessel function (collateral conductance) in a rat model of peripheral vascular disease (femoral artery occlusion), diabetes mellitus type II (Zucker fatty diabetic rats and Zucker lean rat controls) and arterial hypertension (induced via clip placement around the right renal arteriy). We furthermore tested the impact of monocyte chemoattractant protein-1 (MCP‑1) on collateral proliferation and macrophage accumulation in these models Diabetic animals showed reduced vascular proliferation and macrophage accumulation, which however did not translate into a change of collateral conductance. Hypertensive animals on the contrary had reduced collateral conductances without altered macrophage accumulation and only a marginal reduction in collateral proliferation. Infusion of MCP‑1 only enhanced vascular proliferation in diabetic animals. These findings illustrate that impaired monocyte/macrophage recruitment is responsible for reduced collateral growth under diabetic conditions but not in arterial hypertension suggesting that diabetes mellitus in particular affects early stages of collateral growth whereas hypertension has its impact on later remodeling stages. Successful pro-arteriogenic treatment strategies in a patient population that presents with diabetes mellitus and arterial hypertension need to address different stages of collateral growth and thus different molecular and cellular targets simultaneously.

  17. Asymmetric dimethylarginine and coronary collateral vessel development.

    Science.gov (United States)

    Kocaman, Sinan Altan; Sahinarslan, Asife; Biberoglu, Gursel; Hasanoglu, Alev; Akyel, Ahmet; Timurkaynak, Timur; Cengel, Atiye

    2008-11-01

    Nitric oxide (NO) plays a major role in collateral vessel development. Asymmetric dimethylarginine (ADMA) that is an endogenous inhibitor of NO synthesis may impair the effective coronary collateral vessel development. The aim of this study was to evaluate the relationship between plasma ADMA level and coronary collateral vessel development. The patients with a greater than or equal to 95% obstruction in at least one epicardial coronary artery were included in the study. Degree of coronary collateral development was determined according to Rentrop method. Patients with grade 2-3 collateral development were regarded as good collateral group and formed group I. The patients with grade 0-1 collateral development were regarded as poor collateral group and were included in group II. Group III that had been formed as a control group included the patients with a normal coronary angiogram. We compared the plasma ADMA, symmetric dimethylarginine, L-arginine/ADMA ratio among three groups. Seventy-four patients have been included in the study. Patients with good collateral development had lower plasma ADMA level in comparison with patients with poor collateral development (0.41+/-0.25 micromol/l vs. 0.70+/-0.23 micromol/l, P=0.001) and had similar plasma ADMA levels with the patients who have normal coronary arteries. When we compared L-arginine/ADMA ratio between good and poor collateral groups, we found that the patients with higher L-arginine/ADMA ratio have significantly better collateral development (270.8+/-168.0 vs. 120.9+/-92.1, P<0.001). In the analyses comparing Rentrop score with ADMA level and L-arginine/ADMA ratio, there were significant correlations (r=-0.444, P=0.008 and r=0.553, P=0.001, respectively). In multivariate analysis, ADMA level (odds ratio, 0.009; 95% confidence interval, 0.000-0.466, P=0.020) and L-arginine/ADMA ratio (odds ratio, 1.010; 95% confidence interval, 1.001-1.020, P=0.032) were independent predictors of collateral development. Increased

  18. Multiple coil closure of isolated aortopulmonary collateral

    Directory of Open Access Journals (Sweden)

    Padhi Sumanta

    2010-01-01

    Full Text Available A 7-month-old girl was diagnosed to have large aortopulmonary collateral during evaluation for congestive heart failure. There was no other evidence of cardiopulmonary disease. The collateral was successfully closed with multiple coils delivered sequentially. We describe the issues associated during closure of the aortopulmonary collateral in this case. To the best of our knowledge, this is the first reported case of large aortopulmonary collateral presenting with heart failure in an otherwise structurally normal heart that was closed successfully with multiple coils delivered sequentially.

  19. Pioglitazone inhibition of lipopolysaccharide-induced nitric oxide synthase is associated with altered activity of p38 MAP kinase and PI3K/Akt

    Directory of Open Access Journals (Sweden)

    Hunter Randy

    2008-01-01

    Full Text Available Abstract Background Previous studies have suggested that peroxisome proliferator activated receptor-gamma (PPAR-γ-mediated neuroprotection involves inhibition of microglial activation and decreased expression and activity of inducible nitric oxide synthase (iNOS; however, the underlying molecular mechanisms have not yet been well established. In the present study we explored: (1 the effect of the PPAR-γ agonist pioglitazone on lipopolysaccharide (LPS-induced iNOS activity and nitric oxide (NO generation by microglia; (2 the differential role of p38 mitogen-activated protein kinase (p38 MAPK, c-Jun NH(2-terminal kinase (JNK, and phosphoinositide 3-kinase (PI3K on LPS-induced NO generation; and (3 the regulation of p38 MAPK, JNK, and PI3K by pioglitazone. Methods Mesencephalic neuron-microglia mixed cultures, and microglia-enriched cultures were treated with pioglitazone and/or LPS. The protein levels of iNOS, p38 MAPK, JNK, PPAR-γ, PI3K, and protein kinase B (Akt were measured by western blot. Different specific inhibitors of iNOS, p38MAPK, JNK, PI3K, and Akt were used in our experiment, and NO generation was measured using a nitrite oxide assay kit. Tyrosine hydroxylase (TH-positive neurons were counted in mesencephalic neuron-microglia mixed cultures. Results Our results showed that pioglitazone inhibits LPS-induced iNOS expression and NO generation, and inhibition of iNOS is sufficient to protect dopaminergic neurons against LPS insult. In addition, inhibition of p38 MAPK, but not JNK, prevented LPS-induced NO generation. Further, and of interest, pioglitazone inhibited LPS-induced phosphorylation of p38 MAPK. Wortmannin, a specific PI3K inhibitor, enhanced p38 MAPK phosphorylation upon LPS stimulation of microglia. Elevations of phosphorylated PPAR-γ, PI3K, and Akt levels were observed with pioglitazone treatment, and inhibition of PI3K activity enhanced LPS-induced NO production. Furthermore, wortmannin prevented the inhibitory effect of

  20. Regulation of insulin degrading enzyme activity by obesity-associated factors and pioglitazone in liver of diet-induced obese mice.

    Directory of Open Access Journals (Sweden)

    Xiuqing Wei

    Full Text Available Insulin degrading enzyme (IDE is a potential drug target in the treatment of type 2 diabetes (T2D. IDE controls circulating insulin through a degradation-dependent clearance mechanism in multiple tissues. However, there is not sufficient information about IDE regulation in obesity. In this study, we test obesity-associated factors and pioglitazone in the regulation of IDE in diet-induced obese (DIO C57BL/6 mice. The enzyme activity and protein level of IDE were increased in the liver of DIO mice. Pioglitazone (10 mg/kg/day administration for 2 months significantly enhanced the enzyme activity (75%, protein (180% and mRNA (100% of IDE in DIO mice. The pioglitazone-induced changes were coupled with 50% reduction in fasting insulin and 20% reduction in fasting blood glucose. The mechanism of IDE regulation in liver was investigated in the mouse hepatoma cell line (Hepa 1c1c7 cells, in which pioglitazone (5 µM increased IDE protein and mRNA in a time-dependent manner in an 8 h study. Free fatty acid (palmitate 300 µM induced IDE protein, but reduced the mRNA. Glucagon induced, and TNF-α decreased IDE protein. Insulin did not exhibit any activity in the same condition. In summary, pioglitazone, FFA and glucagon directly increased, but TNF-α decreased the IDE activity in hepatocytes. The results suggest that IDE activity is regulated in liver by multiple factors in obesity and pioglitazone may induce IDE activity in the control of T2D.

  1. Toxicological evaluation of subchronic use of pioglitazone in mice

    Directory of Open Access Journals (Sweden)

    Said Said Elshama

    2016-07-01

    Full Text Available Objective(s: Pioglitazone (Actos is one of the most controversial recent oral antidiabetic drugs. It was originally authorized in the European Union in 2000, and approved as an oral monotherapy for overweight second type of diabetic patients in 2002. It belongs to the thiazolidinedione group which some of its members have been withdrawn from the market due to the hepatotoxicity or cardiotoxicity effects.This studyinvestigates sub-chronic use of pioglitazone induced toxicity in mice by the assessment of renal and liver function tests, cardiac enzymes, and some hematological indices with histological changes of liver, kidney, heart, and bladder. Materials and Methods: 120 albino mice were divided into four groups; 30 in each. The first group (control received water, second (diabetic group received alloxan only, while the third and the fourth groups received alloxan with 200 and 400 mg/kg/day of pioglitazone, respectively for 90 days. Results: Prolonged use of pioglitazone induced significant abnormalities of hepatic, renal, and cardiac biomarkers and some hematological indices associated with histopathological changes in the liver, kidney, heart, and bladder that increased based on administered dose. Conclusion: Subchronic use of pioglitazone leads to hepatic, renal, cardiac, hematological, and bladder affection depending on the applied dose.

  2. Temporal patterns of blood flow and nitric oxide synthase expression affect macrophage accumulation and proliferation during collateral growth

    Directory of Open Access Journals (Sweden)

    Sager Hendrik B

    2010-09-01

    Full Text Available Abstract Background The involvement of collateral blood flow/fluid shear stress, nitric oxide (NO, and macrophages during collateral growth (arteriogenesis is established, but their interplay remains paradoxical. Methods In order to further elucidate the "fluid shear stress/NO/macrophage" paradox, we investigated the time course of collateral blood flow (using a Doppler flow probe and NOS expression (immunohistochemistry, Western blot in growing rat collateral vessels after femoral artery occlusion and their impact on macrophage recruitment and collateral proliferation (immunohistochemistry, angiographies. Results (values are given as mean ± standard error of mean Early after occlusion, collateral blood flow was significantly reduced (pre- 90.0 ± 4.5 vs. post-occlusion 62.5 ± 5.9 μl/min; p p p p Conclusions We propose the following resolution of the "fluid shear stress/NO/macrophage" paradox: Collateral blood flow and NOS expression are initially reduced during arteriogenesis allowing macrophages to accumulate and therewith enhancing collateral proliferation. After homing of macrophages (24 h after occlusion, collateral blood flow and NOS expression recover in order to join the effects of macrophages for restoring blood flow.

  3. 12 CFR 725.19 - Collateral requirements.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Collateral requirements. 725.19 Section 725.19 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS NATIONAL CREDIT UNION ADMINISTRATION CENTRAL LIQUIDITY FACILITY § 725.19 Collateral requirements. (a)...

  4. 28 CFR 104.47 - Collateral sources.

    Science.gov (United States)

    2010-07-01

    ... compensation, including life insurance, pension funds, death benefits programs, and payments by Federal, State... determining the appropriate value of offsets for pension funds, life insurance and similar collateral sources... contingencies may or may not occur. In cases where the recipients of collateral source compensation are...

  5. Spectrophotometric estimation of pioglitazone hydrochloride in tablet dosage form

    Directory of Open Access Journals (Sweden)

    Basniwal Pawan

    2008-01-01

    Full Text Available Two simple, rapid, and precise methods - linear regression equation (LRE and standard absorptivity - were developed and validated for the estimation of pioglitazone hydrochloride in tablet dosage form. The maximum absorbance (lmax of pioglitazone hydrochloride was found to be 269.8 nm in methanol:water:hydrochloric acid (250:250:1. Beer-Lambert law was obeyed in the concentration range of 10-50 µg/ml, and the standard absorptivity was found to be 253.97 dl/g/cm. Both the methods were validated for linearity, accuracy, precision (days, analysts, and instrument variation, and robustness (solvent composition. The numerical values for all parameters lie within the acceptable limits. Pioglitazone hydrochloride was estimated in the range of 99.58-99.97% by LRE method and 100.25-100.75% by standard absorptivity method. At 99% confidence limit, the F-test value for the methods was found to be 1.8767.

  6. Effect of Pioglitazone on Plasma Levels of Phenytoin in Rats

    Directory of Open Access Journals (Sweden)

    Abolghasem Jouyban

    2013-10-01

    Full Text Available Introduction: Interaction between drugs represents a major clinical concern for health care professionals and their patients. Patients affected by both type 2 diabetes and epilepsy may be prescribed pioglitazone and an anti-epileptic drug such as phenytoin  concurrently. The aim of this study was to consider the interaction of pioglitazone with phenytoin in an experimental model. According to the result of this study, concurrent use of phenytoin and pioglitazone in clinic may cause therapeutic failure of phenytoin which may cause seizures and during seizures the cardiac function may be affected. Material and Methods: Two groups of rats were treated for 30 days. In group 1 (control group saline (10 ml/kg and phenytoin   (30 mg/kg were administered daily by intragastric gavage. In group 2 (test group , pioglitazone (10 mg/kg was administered daily 60 minutes before phenytoin  (30 mg/kg. Two hours after the last intragastric gavage, animals were anesthetized with ether and 2 ml of blood was drawn from the heart into a syringe containing Ethylenediaminetetraacetic (EDTA, and phenytoin  concentration in rat plasma was determined by High performance liquid chromatography (HPLC.The study consisted of 2 groups of 10 male adult Wistar rats. Results: Compared with control group, concurrent use of pioglitazone and phenytoin   was associated with significantly lower mean plasma concentrations of phenytoin : 2.08 ± 0.03  µg/ml VS 1.2 ± 0.02  µg/ml. Conclusion: Concurrent use of pioglitazone and phenytoin was associated with a significant decrease in plasma concentration of phenytoin in this experimental model. In clinic, this interaction may cause seizures and it has been shown that both cardiac and respiratory functions may affected by seizures.

  7. Influence of drug transporters and stereoselectivity on the brain penetration of pioglitazone as a potential medicine against Alzheimer's disease.

    Science.gov (United States)

    Chang, Kai Lun; Pee, Hai Ning; Yang, Shili; Ho, Paul C

    2015-03-11

    Pioglitazone is currently undergoing clinical trials for treatment of Alzheimer's disease (AD). However, poor brain penetration remains an obstacle to development of the drug for such intended clinical uses. In this study, we demonstrate that the inhibition of P-glycoprotein (P-gp) significantly increases brain penetration of pioglitazone, whereas inhibition of breast cancer resistance protein (BCRP) has little effect. We also investigate the stereoselectivity of pioglitazone uptake in the brain. When mice were dosed with racemic pioglitazone, the concentration of (+)-pioglitazone was 46.6% higher than that of (-)-pioglitazone in brain tissue and 67.7% lower than that of (-)-pioglitazone in plasma. Dosing mice with pure (+)-pioglitazone led to a 76% increase in brain exposure levels compared to those from an equivalent dose of racemic pioglitazone. Pure (+)-pioglitazone was also shown to have comparable amyloid-lowering capabilities to the racemic pioglitazone in an in vitro AD model. These results suggest that P-gp may act as a stereoselective barrier to prevent pioglitazone entry into the brain. Dosing with (+)-pioglitazone instead of the racemic mixture may result in higher levels of brain exposure to pioglitazone, thus potentially improving the development of pioglitazone treatment of AD.

  8. Peripheral Biomarkers of Parkinson's Disease Progression and Pioglitazone Effects.

    Science.gov (United States)

    Simon, David K; Simuni, Tanya; Elm, Jordan; Clark-Matott, Joanne; Graebner, Allison K; Baker, Liana; Dunlop, Susan R; Emborg, Marina; Kamp, Cornelia; Morgan, John C; Ross, G Webster; Sharma, Saloni; Ravina, Bernard

    2015-01-01

    Pioglitazone, an oral hypoglycemic agent, recently failed to show promise as a disease-modifying agent in a 44-week phase 2 placebo-controlled study in 210 Parkinson's disease (PD) subjects. We analyzed peripheral biomarkers, including leukocyte PGC-1α and target gene expression, plasma interleukin 6 (IL-6) as a marker of inflammation, and urine 8-hydroxydeoxyguanosine (8OHdG) as a marker of oxidative DNA damage. Baseline or changes from baseline in biomarker levels were not associated with the rate of progression of PD. Pioglitazone did not significantly alter biomarker levels. Other agents that more effectively target these mechanisms remain of potential interest as disease modifying therapies in PD.

  9. Cannabis, Collaterals, and Coronary Occlusion

    Directory of Open Access Journals (Sweden)

    Kalpa De Silva

    2011-01-01

    Full Text Available A 51-year-old gentleman, who regularly smoked cannabis, presented with chest pain and diaphoresis. He was haemodynamically stable. ECG showed ST depression, inferiorly, and 1 mm ST elevation in lead aVR. Emergent coronary angiography showed thrombotic occlusion of the left main coronary artery (LMCA, the dominant RCA provided Rentrop grade II collaterals to the LAD. The LMCA was successfully reopened by deployment of a bare-metal stent. Animal heart models suggest that endogenous cannibinoids may cause ischaemic preconditioning. This case suggests that the severity of ischaemia, and hence ECG changes and haemodynamic consequences following an acute occlusion of the LMCA, can be ameliorated by coronary collateralisation and possibly by preconditioning of the myocardium.

  10. A review of pioglitazone HCL and glimepiride in the treatment of type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Mozhgan Dorkhan

    2007-11-01

    Full Text Available Mozhgan Dorkhan, Anders FridDepartment of Clinical Sciences, Division of Diabetes and Endocrinology, Lund University, Malmö University Hospital, SwedenAbstract: Type 2 diabetes (T2D is a progressive disorder with a consistent and steady increase in glycosylated hemoglobin (HbA1c over time associated with enhanced risk of micro- and macrovascular complications and a substantial reduction in life expectancy. There are three major pathophysiologic abnormalities associated with T2D: impaired insulin secretion, excessive hepatic glucose output, and insulin resistance in skeletal muscle, liver, and adipose tissue. These defects have been treated in clinical praxis by use of oral insulin secretagogues (sulfonylureas/glinides or insulin, biguanides, and thiazolidinediones (TZDs respectively. Pioglitazone HCL is an insulin sensitizer in the TZD family and glimepiride is an insulin secretagogue in the SU family. This article reviews mechanisms of action and clinical data behind the use of these two commonly used oral hypoglycemic agents with documented efficacy and good safety profile of once-daily administration, alone or in combination with insulin or metformin, in the management of T2D in terms of glycemic and non-glycemic effects, tolerability and side effects, and impact on vascular health.Keywords: pioglitazone, glimepiride, type 2 diabetes, thiazolidinediones, sulfonylureas

  11. Effect of pioglitazone treatment on behavioral symptoms in autistic children

    Directory of Open Access Journals (Sweden)

    Edelson Stephen M

    2007-01-01

    Full Text Available Abstract Introduction Autism is complex neuro-developmental disorder which has a symptomatic diagnosis in patients characterized by disorders in language/communication, behavior, and social interactions. The exact causes for autism are largely unknown, but is has been speculated that immune and inflammatory responses, particularly those of Th2 type, may be involved. Thiazolidinediones (TZDs are agonists of the peroxisome proliferator activated receptor gamma (PPARγ, a nuclear hormone receptor which modulates insulin sensitivity, and have been shown to induce apoptosis in activated T-lymphocytes and exert anti-inflammatory effects in glial cells. The TZD pioglitazone (Actos is an FDA-approved PPARγ agonist used to treat type 2 diabetes, with a good safety profile, currently being tested in clinical trials of other neurological diseases including AD and MS. We therefore tested the safety and therapeutic potential of oral pioglitazone in a small cohort of children with diagnosed autism. Case description The rationale and risks of taking pioglitazone were explained to the parents, consent was obtained, and treatment was initiated at either 30 or 60 mg per day p.o. A total of 25 children (average age 7.9 ± 0.7 year old were enrolled. Safety was assessed by measurements of metabolic profiles and blood pressure; effects on behavioral symptoms were assessed by the Aberrant Behavior Checklist (ABC, which measures hyperactivity, inappropriate speech, irritability, lethargy, and stereotypy, done at baseline and after 3–4 months of treatment. Discussion and evaluation In a small cohort of autistic children, daily treatment with 30 or 60 mg p.o. pioglitazone for 3–4 months induced apparent clinical improvement without adverse events. There were no adverse effects noted and behavioral measurements revealed a significant decrease in 4 out of 5 subcategories (irritability, lethargy, stereotypy, and hyperactivity. Improved behaviors were inversely

  12. Acute development of collateral circulation and therapeutic prospects in ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    Eri Iwasawa; Masahiko Ichijo; Satoru Ishibashi; Takanori Yokota

    2016-01-01

    In acute ischemic stroke, collateral circulation plays an important role in maintaining blood lfow to the tissue that is at risk of progressing into ischemia, and in increasing the successful recanalization rate with-out hemorrhagic transformation. We have reported that well-developed collateral circulation is associated with smaller infarct volume and better long-term neurological outcome, and it disappears promptly once the effective recanalization is achieved. Contrary to the belief that collateral vessels develop over time in chronic stenotic condition, there exists a phenomenon that collateral circulation develops immediately in acute stenosis or occlusion of the arteries and it seems to be triggered by lfuid shear stress, which occurs be-tween the territories of stenotic/occluded arteries and those fed by surrounding intact arteries. We believe that this acute development of collateral circulation is a target of novel therapeutics in ischemic stroke and refer our recent attempt in enhancing collateral circulation by modulating sphingosine-1-phosphate recep-tor 1, which is a known shear-stress mechanosensing protein.

  13. Use of pioglitazone in the treatment of diabetes: effect on cardiovascular risk.

    Science.gov (United States)

    Zou, Cong; Hu, Honglin

    2013-01-01

    Pioglitazone and other thiazolidinediones (TZDs) initially showed great promise as unique receptor-mediated oral therapy for type 2 diabetes, but a host of serious side effects, primarily cardiovascular, have limited their utility. It is crucial at this point to perform a risk- benefit analysis to determine what role pioglitazone should play in our current treatment of type 2 diabetes and where the future of this class of drugs is headed. This review provides a comprehensive overview of the present literature. Clinical data currently available indicate that pioglitazone is an effective and generally well-tolerated treatment option for use in patients with type 2 diabetes. Pioglitazone can still reduce adverse cardiovascular risk.

  14. Possible link of pioglitazone with bladder cancer in Japanese patients with type 2 diabetes.

    Science.gov (United States)

    Fujimoto, Kanta; Hamamoto, Yoshiyuki; Honjo, Sachiko; Kawasaki, Yukiko; Mori, Kanako; Tatsuoka, Hisato; Matsuoka, Atsuko; Wada, Yoshiharu; Ikeda, Hiroki; Fujikawa, Jun; Koshiyama, Hiroyuki

    2013-02-01

    We retrospectively examined the frequency of bladder cancer in Japanese patients with type 2 diabetes in relation to use of pioglitazone. Among a total of 663 patients identified to be taking pioglitazone, 9 had bladder cancer (1.36%). Overall the hazard ratio of 1.75 [95% CI: 0.89-3.45] for pioglitazone for bladder cancer was not significant. However the prevalence of bladder cancer was 2.10% in patients taking pioglitazone for less than 24 months which was significant increased (HR 2.73 [95% CI: 1.11-6.72]).

  15. Linagliptin and pioglitazone combination therapy versus monotherapy with linagliptin or pioglitazone: A randomised, double-blind, parallel-group, multinational clinical trial.

    Science.gov (United States)

    Nauck, Michael Albrecht; di Domenico, Maximiliano; Patel, Sanjay; Kobe, Maureen; Toorawa, Robert; Woerle, Hans-Juergen

    2016-07-01

    Linagliptin plus pioglitazone single-pill combinations were evaluated. Patients (n = 936) with insufficient glycaemic control, despite lifestyle interventions, were randomised for 30 weeks to either monotherapy with linagliptin 5 mg; pioglitazone 15, 30 or 45 mg; or single-pill combination with linagliptin 5 mg plus pioglitazone 15, 30 or 45 mg. An extension (⩽54 weeks) planned to evaluate linagliptin plus pioglitazone 30 or 45 mg single-pill combinations was not completed due to a protocol amendment. Adjusted mean (95% confidence interval) differences in HbA1c change from baseline at week 30 for linagliptin plus pioglitazone 15, 30 and 45 mg were -0.17% (-0.41, 0.07), -0.37% (-0.60, -0.14) and -0.41% (-0.64, -0.18) versus pioglitazone monotherapies, respectively, and -0.44% (-0.67, -0.20), -0.68% (-0.91, -0.44) and -0.89% (-1.12, -0.66) versus linagliptin monotherapy, respectively. Single-pill combinations were generally well tolerated. Hypoglycaemia frequency was ⩽1.5% per group. Linagliptin plus pioglitazone combinations were efficacious, with safety profiles comparable to the individual monotherapies.

  16. Impact of Slow Blood Filling via Collaterals on Infarct Growth: Comparison of Mismatch and Collateral Status

    Science.gov (United States)

    Son, Jeong Pyo; Lee, Mi Ji; Kim, Suk Jae; Chung, Jong-Won; Cha, Jihoon; Kim, Gyeong-Moon; Chung, Chin-Sang; Lee, Kwang Ho; Bang, Oh Young

    2017-01-01

    Background and Purpose Perfusion-diffusion mismatch has been evaluated to determine whether the presence of a target mismatch helps to identify patients who respond favorably to recanalization therapies. We compared the impact on infarct growth of collateral status and the presence of a penumbra, using magnetic resonance perfusion (MRP) techniques. Methods Consecutive patients who were candidates for recanalization therapy and underwent serial diffusion-weighted imaging (DWI) and MRP were enrolled. A collateral flow map derived from MRP source data was generated by automatic post-processing. The impact of a target mismatch (Tmax>6 s/apparent diffusion coefficient (ADC) volume≥1.8, ADC volume10 s for ADC volume<100 mL) on infarct growth was compared with MR-based collateral grading on day 7 DWI, using multivariate linear regression analysis. Results Among 73 patients, 55 (75%) showed a target mismatch, whereas collaterals were poor in 14 (19.2%), intermediate in 36 (49.3%), and good in 23 (31.5%) patients. After adjusting for initial severity of stroke, early recanalization (P<0.001) and the MR-based collateral grading (P=0.001), but not the presence of a target mismatch, were independently associated with infarct growth. Even in patients with a target mismatch and successful recanalization, the degree of infarct growth depended on the collateral status. Perfusion status at later Tmax time points (beyond the arterial phase) was more closely correlated with collateral status. Conclusions Patients with good collaterals show a favorable outcome in terms of infarct growth, regardless of the presence of a target mismatch pattern. The presence of slow blood filling predicts collateral status and infarct growth. PMID:28030891

  17. Effects and Potential Mechanisms of Pioglitazone on Lipid Metabolism in Obese Diabetic KKAy Mice

    Directory of Open Access Journals (Sweden)

    Jun Peng

    2014-01-01

    Full Text Available This study aimed to analyze the effects and potential mechanisms of pioglitazone on triglyceride and cholesterol metabolism in obese diabetic KKAy mice. Pioglitazone was orally administered to KKAy mice over 30 days. Compared to C57BL/6J mice, KKAy mice developed obvious insulin resistance, hepatic steatosis, and hyperlipidemia. Pioglitazone treatment resulted in deteriorated microvesicular steatosis and elevated hepatic triglyceride levels, though plasma triglyceride and free fatty acid levels were reduced by the treatment, compared to nontreated KKAy mice. Plasma alanine aminotransferase activities were also significantly increased. Additionally, pioglitazone increased plasma concentrations of total cholesterol, HDL-cholesterol, and LDL-cholesterol but decreased hepatic cholesterol. Gene expression profiling revealed that pioglitazone stimulated hepatic peroxisome proliferator-activated receptor gamma hyperactivity, and induced the upregulation of adipocyte-specific and lipogenesis-related genes but downregulated of genes involved in triglyceride lipolysis and fatty acid β-oxidation. Pioglitazone also regulated the genes expression of hepatic cholesterol uptake and excretion, such as low density lipoprotein receptor (LDL-R and scavenger receptor type-BI (SR-BI. These results suggested that pioglitazone could induce excessive hepatic triglyceride accumulation, thus aggravating liver steatosis and lesions in KKAy mice. Furthermore, pioglitazone may suppress the clearance of serum cholesterol from the liver predominantly through inhibition of LDL-R and SR-BI expression, thus increasing the plasma cholesterol.

  18. Effect of method of preparation on pioglitazone HCl-β-cyclodextrin inclusion complexes

    Directory of Open Access Journals (Sweden)

    Beloshe Shrikant

    2010-01-01

    Full Text Available Pioglitazone HCl is an antidiabetic agent with poor aqueous solubility. Inclusion complexes of pioglitazone HCl were prepared with β-cyclodextrin using various methods (physical mixing, kneading method, co-precipitation. The main aim of the present invention is to study the effect of the method of preparation on the dissolution profiles of pioglitazone HCl-β-Cyclodextrin inclusion complexes . The phase solubility profile of pioglitazone HCl with β-cyclodextrin was classified as AL-type and stability constant with 1:1 molar ratio was 115.45, calculated from the phase solubility diagram. Formation of the inclusion complex between pioglitazone HCl and β-cyclodextrin was confirmed by the Fourier Transform Infrared (FT-IR spectroscopy. The dissolution profile of inclusion complexes were determined and compared with those of pioglitazone HCl alone and its physical mixtures. The dissolution rate of the pioglitazone HCl-β-cyclodextrin inclusion complex prepared by the co-precipitation method was six times higher when compared with the pure drug. The method of complexation of pioglitazone HCl in β-CD increased the dissolution rate of the drug in the following order: Coppt > KM > PM >Drug.

  19. Pioglitazone has a dubious bladder cancer risk but an undoubted cardiovascular benefit.

    Science.gov (United States)

    Ryder, R E J

    2015-03-01

    On 8 April 2014, a US jury ordered Takeda and Eli Lilly to pay $9 bn in punitive damages after finding that they had concealed the cancer risks associated with pioglitazone. By contrast, on 28 August 2014, the long-awaited outcome of the 10-year Kaiser Permanente Northern California study was announced. That study was specifically designed to investigate whether patients exposed to pioglitazone were at an increased risk of bladder cancer and found no association; thus, at last, the controversial issue has been resolved. A review, in retrospect, of the story of the proposed link between pioglitazone and bladder cancer reveals flaws at every stage. In 2012, a BMJ editorial, in keeping with some other contemporary reports, stated 'it can confidently be assumed that pioglitazone increases the risk of bladder cancer'. Examination of the information which led to such a statement shows that: 1) the pre-clinical findings of bladder cancer in male rats is not indicative of human risk; 2) there is no association between bladder cancer and pioglitazone in randomized controlled trials, once cases that could not plausibly be related to treatment are removed; and 3) the observational studies that have suggested a link have over-extrapolated from the data: pioglitazone-treated patients had more risk factors for bladder cancer than those not treated with pioglitazone. Meanwhile careful study of randomized controlled trials shows evidence of cardiovascular benefit from pioglitazone in Type 2 diabetes, a condition which results, more than anything, in premature cardiovascular death and morbidity.

  20. Pioglitazone increases the glycolytic efficiency of human Sertoli cells with possible implications for spermatogenesis.

    Science.gov (United States)

    Meneses, M J; Bernardino, R L; Sá, R; Silva, J; Barros, A; Sousa, M; Silva, B M; Oliveira, P F; Alves, M G

    2016-10-01

    Pioglitazone is a synthetic agonist for the nuclear receptor peroxisome proliferator-activated receptor γ used to treat type 2 diabetes mellitus. Recently we reported that antidiabetic drugs regulate the nutritional support of spermatogenesis by Sertoli cells. Herein, we investigate the effects of pioglitazone on human Sertoli cells metabolism. Human Sertoli cells were cultured in the presence of pioglitazone (1, 10, 100μM). Protein levels of phosphofructokinase 1, lactate dehydrogenase, hexokinase, glucose transporters (GLUT1, GLUT2, GLUT3), monocarboxylate transporter 4 and oxidative phosphorylation complexes were determined by Western blot. Lactate dehydrogenase and alanine aminotransferase activity were assessed and metabolite production and consumption determined by proton nuclear magnetic resonance. Mitochondrial membrane potential was also determined. Glucose consumption more than doubled in human Sertoli cells stimulated with pioglitazone 100μM. Mitochondrial complex II protein levels increased 50% with exposure to pioglitazone (100μM) in human Sertoli cells, though mitochondrial membrane potential was decreased by 32%. The pharmacological concentration of pioglitazone (10μM) almost doubled lactate production and established crucial correlations among key intervenient of glycolysis. Moreover, in the same concentration, alanine aminotransferase decreased more than 80%. Our results suggest that pioglitazone (10μM) increases the efficiency of the glycolytic flux and lactate production by human Sertoli cells, which is essential to sustain and preserve the spermatogenic event. Thus, pioglitazone may improve male fertility and thus, be considered a suitable antidiabetic drug for men in reproductive age.

  1. 7 CFR 762.142 - Servicing related to collateral.

    Science.gov (United States)

    2010-01-01

    ... collateral. (6) Ensure the loan and the collateral are protected in the event of foreclosure, bankruptcy... not be released unless it is being replaced and business assets will not be released for use as a gift...

  2. Pioglitazone promotes preadipocyte proliferation by downregulating p16(Ink4a).

    Science.gov (United States)

    Hasan, Arif U; Ohmori, Koji; Hashimoto, Takeshi; Kamitori, Kazuyo; Hirata, Yuko; Ishihara, Yasuhiro; Okamoto, Naoko; Noma, Takahisa; Kosaka, Hiroaki; Tokuda, Masaaki; Kohno, Masakazu

    2011-07-29

    Pioglitazone, a synthetic ligand of peroxisome proliferator-activated receptor (PPAR)γ, causes preadipocyte proliferation through a mechanism which still remains elusive. Here, to address the mechanism, we investigated the effects of PPARγ and pioglitazone on the kinetics of cyclin-dependent kinase inhibitors, especially with p16(Ink4a) (p16) centered, by employing 3T3-L1 preadipocytes. Pioglitazone promoted preadipocyte proliferation by increasing S and G(2)/M cell-cycle entry, which was accompanied by decreased p16 mRNA expression. PPARγ overexpression along with the luciferase reporter assay confirmed that PPARγ was crucial for the downregulation of p16 mRNA transcription, and that the action was augmented by pioglitazone. Thus, pioglitazone exerted cell-cycle dependent promoting effect on preadipocyte proliferation, of which mechanisms include p16-downregulation through PPARγ. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Reduced serum dipeptidyl peptidase-IV after metformin and pioglitazone treatments.

    Science.gov (United States)

    Lenhard, James M; Croom, Dallas K; Minnick, Dana T

    2004-11-05

    Dipeptidyl peptidase-IV (DPP-IV) regulates metabolism by degrading incretins involved in nutritional regulation. Metformin and pioglitazone improve insulin sensitivity whereas glyburide promotes insulin secretion. Zucker diabetic rats were treated with these antidiabetic agents for 2 weeks and DPP-IV activity and expression were determined. Serum DPP-IV activity increased whereas tissue activity decreased as the rats aged. Treatment of rats with metformin, pioglitazone, and glyburide did not alter DPP-IV mRNA expression in liver or kidney. Metformin and pioglitazone significantly (PMetformin, pioglitazone, and glyburide had no effect on serum DPP-IV activity in vitro, indicating these are not competitive DPP-IV inhibitors. We propose the in vivo inhibitory effects observed with metformin and pioglitazone on serum DPP-IV activity results from reduced DPP-IV secretion.

  4. Coronary collaterals improve prognosis in patients with ischemic heart disease

    NARCIS (Netherlands)

    J.J. Regieli; J.W. Jukema; H.M. Nathoe; A.H. Zwinderman; S. ng; D.E. Grobbee; Y. van der Graaf; P.A. Doevendans

    2009-01-01

    BACKGROUND: The recruitment of coronary collateral vessels results from an endogenous adaptation to ischemic heart disease (IHD). Presence of collaterals may exert protection at the time of acute or chronic obstructive coronary disease. The protective role of collaterals in patients with extensive c

  5. Impaired insulin-stimulated phosphorylation of Akt and AS160 in skeletal muscle of women with polycystic ovary syndrome is reversed by pioglitazone treatment

    DEFF Research Database (Denmark)

    Højlund, Kurt; Glintborg, Dorte; Andersen, Nicoline Resen

    2008-01-01

    OBJECTIVE: Insulin resistance in skeletal muscle is a major risk factor for type 2 diabetes in women with polycystic ovary syndrome (PCOS). However, the molecular mechanisms underlying skeletal muscle insulin resistance and the insulin-sensitizing effect of thiazolidinediones in PCOS in vivo...... in muscle of PCOS patients. Akt phosphorylation at Ser473 and Thr308 correlated positively with R(d) and NOGD in the insulin-stimulated state. Serum free testosterone was inversely related to insulin-stimulated R(d) and NOGD in PCOS. Importantly, the pioglitazone-mediated improvement in insulin....... CONCLUSIONS: Impaired insulin signaling through Akt and AS160 in part explains insulin resistance at the molecular level in skeletal muscle in PCOS, and the ability of pioglitazone to enhance insulin sensitivity involves improved signaling through Akt and AS160. Moreover, our data provide correlative evidence...

  6. Debt capacity of real estate collateral

    NARCIS (Netherlands)

    Giambona, E.; Golec, J.; Schwienbacher, A.

    2014-01-01

    We study whether real estate assets have a greater positive influence on firm leverage than other tangible assets. Using a large sample of COMPUSTAT firms, we find a significant positive relation between tangibility and leverage in general, and the relation is strongest for real estate collateral.

  7. Trade credit, collateral liquidation and borrowing constraints

    NARCIS (Netherlands)

    Fabbri, D.; Menichini, A.M.C.

    2009-01-01

    The paper proposes a model of collateralized bank and trade credit. Firms use a two-input technology. Assuming that the supplier is better able to extract value from existing assets and has an information advantage over other creditors, the paper derives a series of predictions. (1) Financially

  8. 31 CFR 202.6 - Collateral security.

    Science.gov (United States)

    2010-07-01

    ... 202.6 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE DEPOSITARIES AND FINANCIAL AGENTS OF THE FEDERAL... depositary authorized to perform services under § 202.3(b) must pledge collateral security in the amount...

  9. 12 CFR 614.4240 - Collateral definitions.

    Science.gov (United States)

    2010-01-01

    ...) Real property means all interests, benefits, and rights inherent in the ownership of real estate. (r... income and/or other collateral, absent the real estate, and the decision to extend credit was, in fact... staff evaluator from another Farm Credit System institution only if the employing institution is not...

  10. 30 CFR 800.21 - Collateral bonds.

    Science.gov (United States)

    2010-07-01

    ... appraisal conducted by a certified appraiser; and (iii) Proof of possession and title to the real property.... (a) Collateral bonds, except for letters of credit, cash accounts, and real property, shall be... by a bank organized or authorized to do business in the United States; (2) Letters of credit shall...

  11. Characterization of pioglitazone cyclodextrin complexes: Molecular modeling to in vivo evaluation

    Science.gov (United States)

    Bramhane, Dinesh M.; Kulkarni, Preethi A.; Martis, Elvis A. F.; Pissurlenkar, Raghuvir R. S.; Coutinho, Evans C.; Nagarsenker, Mangal S.

    2016-01-01

    Aims: The objective of present study was to study the influence of different β-cyclodextrin derivatives and different methods of complexation on aqueous solubility and consequent translation in in vivo performance of Pioglitazone (PE). Material and Methods: Three cyclodextrins: β-cyclodextrin (BCD), hydroxypropyl-β-cyclodextrin (HPBCD) and Sulfobutylether-7-β-cyclodextrin (SBEBCD) were employed in preparation of 1:1 Pioglitazone complexes by three methods viz. co-grinding, kneading and co-evaporation. Complexation was confirmed by phase solubility, proton NMR, Fourier Transform Infrared spectroscopy, Differential Scanning Calorimetry (DSC) and X-Ray diffraction (XRD). Mode of complexation was investigated by molecular dynamic studies. Pharmacodynamic study of blood glucose lowering activity of PE complexes was performed in Alloxan induced diabetic rat model. Results: Aqueous solubility of PE was significantly improved in presence of cyclodextrin. Apparent solubility constants were observed to be 254.33 M–1 for BCD-PE, 737.48 M–1 for HPBCD-PE and 5959.06 M–1 for SBEBCD-PE. The in silico predictions of mode of inclusion were in close agreement with the experimental proton NMR observation. DSC and XRD demonstrated complete amorphization of crystalline PE upon inclusion. All complexes exhibited >95% dissolution within 10 min compared to drug powder that showed <40% at the same time. Marked lowering of blood glucose was recorded for all complexes. Conclusion: Complexation of PE with different BCD significantly influenced its aqueous solubility, improved in vitro dissolution and consequently translated into enhanced pharmacodynamic activity in rats PMID:27134470

  12. Characterization of pioglitazone cyclodextrin complexes: Molecular modeling to in vivo evaluation

    Directory of Open Access Journals (Sweden)

    Dinesh M Bramhane

    2016-01-01

    Full Text Available Aims: The objective of present study was to study the influence of different β-cyclodextrin derivatives and different methods of complexation on aqueous solubility and consequent translation in in vivo performance of Pioglitazone (PE. Material and Methods: Three cyclodextrins: β-cyclodextrin (BCD, hydroxypropyl-β-cyclodextrin (HPBCD and Sulfobutylether-7-β-cyclodextrin (SBEBCD were employed in preparation of 1:1 Pioglitazone complexes by three methods viz. co-grinding, kneading and co-evaporation. Complexation was confirmed by phase solubility, proton NMR, Fourier Transform Infrared spectroscopy, Differential Scanning Calorimetry (DSC and X-Ray diffraction (XRD. Mode of complexation was investigated by molecular dynamic studies. Pharmacodynamic study of blood glucose lowering activity of PE complexes was performed in Alloxan induced diabetic rat model. Results: Aqueous solubility of PE was significantly improved in presence of cyclodextrin. Apparent solubility constants were observed to be 254.33 M–1 for BCD-PE, 737.48 M–1 for HPBCD-PE and 5959.06 M–1 for SBEBCD-PE. The in silico predictions of mode of inclusion were in close agreement with the experimental proton NMR observation. DSC and XRD demonstrated complete amorphization of crystalline PE upon inclusion. All complexes exhibited >95% dissolution within 10 min compared to drug powder that showed <40% at the same time. Marked lowering of blood glucose was recorded for all complexes. Conclusion: Complexation of PE with different BCD significantly influenced its aqueous solubility, improved in vitro dissolution and consequently translated into enhanced pharmacodynamic activity in rats

  13. Effects of pioglitazone and metformin on vascular endothelial function in patients with type 2 diabetes treated with sulfonylureas.

    Science.gov (United States)

    Naka, Katerina K; Papathanassiou, Katerina; Bechlioulis, Aris; Pappas, Konstantinos; Kazakos, Nikolaos; Kanioglou, Chryssanthi; Kostoula, Aggeliki; Vezyraki, Patra; Makriyiannis, Demetrios; Tsatsoulis, Agathocles; Michalis, Lampros K

    2012-01-01

    Pioglitazone and metformin are insulin sensitisers used for the treatment of T2DM. The effects of pioglitazone and metformin on endothelial function, assessed by FMD, in T2DM patients treated with sulfonylureas were compared. Patients were randomised to receive pioglitazone (n = 15) 30 mg once daily or metformin (n = 16) 850 mg twice daily for six months. Pioglitazone significantly decreased fasting insulin, HbA(1C) and HOMA-IR (p pioglitazone, compared with metformin, did not reach significance (p = 0.11). Treatment-induced changes in FMD were not associated with the effects of the two insulin sensitisers on glycaemic control or insulin resistance. The beneficial effects of pioglitazone and metformin on endothelial function in T2DM patients did not differ greatly. Larger studies are needed to explore whether a potentially greater benefit with pioglitazone may exist.

  14. Effects of pioglitazone on platelet P2Y12-mediated signalling in clopidogrel-treated patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Suryadevara, Siva; Ueno, Masafumi; Tello-Montoliu, Antonio; Ferreiro, Jose Luis; Desai, Bhaloo; Rollini, Fabiana; Box, Lyndon C; Zenni, Martin; Guzman, Luis A; Bass, Theodore A; Angiolillo, Dominick J

    2012-11-01

    Patients with type 2 diabetes mellitus (T2DM) have impaired clopidogrel-induced antiplatelet effects, which may be in part attributed to their reduced sensitivity to insulin and consequently, results in upregulation of the P2Y12 signalling pathway. It has been hypothesised that insulin sensitising strategies may enhance clopidogrel-mediated P2Y12 inhibitory effects. The aim of this pilot pharmacodynamics (PD) study was to assess the impact of pioglitazone on clopidogrel-mediated P2Y12 inhibitory effects in patients with T2DM. This was a prospective, randomised, double-blind, placebo-controlled, cross-over PD study. Patients with T2DM and stable coronary artery disease on maintenance aspirin and clopidogrel were randomised to receive either pioglitazone 30 mg or matching placebo daily for 14 days. PD assessments were measured at baseline, 14 days after randomisation, at the end of the wash-out period, and 14 days after cross-over. The primary endpoint measure was maximal platelet aggregation (MPA) to 20 μM adenosine diphosphate (ADP) as assessed by light transmittance aggregometry (LTA). Flow cytometric analysis of vasodilator-stimulated phosphoprotein phosphorylation (VASP-PRI), and VerifyNow P2Y12 testing were also performed. A total of 15 randomised patients completed the study. MPA to 20 μM ADP (primary endpoint) was not significantly different with pioglitazone compared with placebo (49.53 ± 4.76 vs. 52.52 ± 3.89%; p = 0.594). Similarly, other PD measures did not differ significantly between the groups. In conclusion, in patients with T2DM on maintenance aspirin and clopidogrel therapy, the adjunctive use of pioglitazone does not result in enhanced inhibition of platelet P2Y12 mediated signalling.

  15. Effects of PPARg agonist pioglitazone on rat hepatic fibrosis

    Institute of Scientific and Technical Information of China (English)

    Guang-Jin Yuan; Ming-Liang Zhang; Zuo-Jiong Gong

    2004-01-01

    AIM: To investigate effects of pioglitazone on rat hepatic fibrosis and to explore its mechanism.METHODS: Rat hepatic fibrosis was induced by carbon tet:achloride (CCl4). Forty Sprague-Dawley rats were divided randomly into 4 groups: control, model, and two treatment (PⅠ, PⅡ) groups. Except for rats in control group, all rats were given subcutaneous injection of 400 mL/L CCl4, twice a wk for 8 wk. Rats in PⅠ and PⅡ groups were also treated with pioglitazone of 3 mg/kg, daily via gastrogavage beginning on the 1st day and at the end of the 2nd week,administration of CCl4 respectively. Liver functions (ALT,AST), serum fibrotic markers (HA, LN, PCⅢ) and hepatic hydroxyproline (HP) concentration were determined respectively. Histochemical staining of formalin-fixed liver sections with HE, Masson-Trichrome, and immunohistochemical staining for α-smooth muscle actin (α-SMA) were performed.Modified Knodell and Chevallier semi-quantitative scoring system (SSS) was used to evaluate necroinflammatory activity and fibrosis degree.RESULTS: Compared with model group, pioglitazone significantly reduced the serum levels of ALT, AST, HA, LN and PCⅢ (P<0.05 or <0.01). The HP concentrations in PⅠ (210.90±24.07 μg/g), and PⅡ (257.36±30.55 μg/g) groups were also lower than those in model group (317.80±36.44 μg/g) (P<0.01). Histologic examination showed that PⅠ and PⅡ groups had milder hepatocellular degeneration, necrosis and infiltration of inflammatory cells, and thinner or less fibrotic septa than did model group. The scores for necroinflammation in PⅠ (2.80±1.03), and PⅡ (3.00±1.05) groups were significantly reduced as compared with model group (4.88±2.30) (P<0.05 or <0.01); the fibrosis scores in PⅠ (3.40±1.65), and PⅡ (4.60±1.35) groups were also markedly lower than those in model group (7.00±3.21)(P<0.05 or <0.01). Immunohistochemical staining showed that expression of α-SMA in PⅠ and PⅡ groups was ameliorated

  16. Pioglitazone attenuates tactile allodynia and thermal hyperalgesia in mice subjected to peripheral nerve injury.

    Science.gov (United States)

    Maeda, Takehiko; Kiguchi, Norikazu; Kobayashi, Yuka; Ozaki, Masanobu; Kishioka, Shiroh

    2008-11-01

    To clarify the role of peroxisome proliferator activated receptor gamma (PPARgamma) in neuropathic pain, we examined the effect of pioglitazone, a PPARgamma agonist, on tactile allodynia and thermal hyperalgesia in a neuropathic pain model. Mice were subjected to partial sciatic nerve ligation (PSL) and given pioglitazone (1 - 25 mg/kg, p.o.) once daily. PPARgamma was distributed in the neurons of the dorsal root ganglion and the dorsal horn of the spinal cord and in the adipocytes at the epineurium of the sciatic nerve in naive mice. PSL elicited tactile allodynia and thermal hyperalgesia for two weeks. Administration of pioglitazone for the first week after PSL attenuated thermal hyperalgesia and tactile allodynia, which was dose-dependent and blocked by GW9662 (2 mg/kg, i.p.), a PPARgamma antagonist. Administration of pioglitazone for the second week also relieved tactile allodynia, but administration one week before PSL had no effect. A single administration of pioglitazone to mice on day 7 of PSL did not alter tactile allodynia and thermal hyperalgesia. PSL-induced upregulation of tumor necrosis factor-alpha and interleukin-6, which are essential for neuropathic pain, was suppressed by pioglitazone for the first week. This suggests that pioglitazone alleviates neuropathic pain through attenuation of proinflammatory cytokine upregulation by PPARgamma stimulation.

  17. Pioglitazone does not affect vascular or inflammatory responses after endotoxemia in humans.

    Science.gov (United States)

    Schaller, G; Kolodjaschna, J; Pleiner, J; Mittermayer, F; Kapiotis, S; Schmetterer, L; Wolzt, M

    2008-08-01

    PPARgamma agonists have been proposed to exert more than metabolic benefits, particularly by anti-inflammatory mechanisms. We hypothesized that pioglitazone might modulate inflammatory and vascular responses to lipopolysaccharide (LPS). In a placebo-controlled parallel-group study in 18 healthy male subjects, the E. coli endotoxin model of inflammation (20 IU/kg i. v.) was employed to test the effect of 60 mg pioglitazone over nine days on inflammatory cytokines. Macrovascular function and microvascular blood flow were assessed by brachial artery ultrasound and retinal blood flow parameters, respectively. Pioglitazone increased brachial artery diameter by 5.6% but had no effect on other outcome parameters under resting conditions. LPS increased cytokine levels to peak concentrations of 91.3+/-22.5 ng/ml (IL-6), 261.4+/-60.0 ng/ml (TNFalpha), and 524.5+/-15.3 ng/ml (VCAM-1). The endotoxin caused microvascular vasodilation and increased retinal white blood cell flux, while baseline brachial artery diameter remained unchanged. Pioglitazone had no effect on inflammatory cytokine or adhesion molecule release but mitigated LPS-induced hypotension (p<0.05). Neither brachial artery function nor microvascular blood flow was altered by pioglitazone. In conclusion, acute immune reactions to LPS are not affected by pioglitazone, which exerts subtle vascular effects alone and during endotoxemia. The anti-inflammatory properties of short-term pioglitazone to endotoxins in healthy subjects are therefore limited.

  18. Direct inhibitory effects of pioglitazone on hepatic fetuin-A expression.

    Directory of Open Access Journals (Sweden)

    Akinobu Ochi

    Full Text Available Fetuin-A, a circulating glycoprotein synthesized in the liver, is involved in insulin resistance and type 2 diabetes. However, regulation of fetuin-A synthesis has remained obscure. We previously reported that pioglitazone treatment significantly reduced serum fetuin-A levels in patients with type 2 diabetes. To clarify whether pioglitazone can directory inhibit hepatic fetuin-A synthesis, we investigated the effects of pioglitazone on fetuin-A expression both in vitro and in vivo. Pioglitazone treatment suppressed mRNA and protein expression of fetuin-A in Fao hepatoma cells. Interestingly, rosiglitazone but not metformin, also inhibited fetuin-A expression. In addition, GW 9662, an inhibitor of peroxisome proliferator-activated receptor (PPAR γ, reversed pioglitazone-induced suppression of fetuin-A, suggesting that thiazolidinedione derivatives may have common characteristics with regard to fetuin-A suppression, possibly through PPARγactivation. Finally, oral administration of pioglitazone to mice for 8 weeks resulted in suppression of hepatic fetuin-A mRNA. These findings suggest that pioglitazone may partially ameliorate insulin resistance through its direct inhibitory effects on fetuin-A expression in the liver.

  19. Treatment with pioglitazone is associated with decreased preprandial ghrelin levels: a randomized clinical trial.

    Science.gov (United States)

    Taslimi, Shervin; Esteghamati, Alireza; Rashidi, Armin; Tavakkoli, Hosein Moin; Nakhjavani, Manouchehr; Kebriaee-Zadeh, Abbas

    2013-02-01

    The effects of metformin and pioglitazone on ghrelin, a physiologic regulator of appetite and food intake, have not been clearly established. In a randomized clinical trial, we randomly assigned 60 type 2 diabetic patients to either metformin (Group A; n=30) or pioglitazone (Group B; n=30) treatment groups. The groups were similar in their baseline characteristics. A standard fasting 75 g oral glucose tolerance test was performed at time zero before starting metformin or pioglitazone, and 3 months later. After 3 months of treatment, pioglitazone, but not metformin, was significantly associated with weight gain. Both groups experienced a significant reduction in fasting plasma glucose (ppioglitazone group had a significant reduction in preprandial ghrelin levels after treatment (ppioglitazone on ghrelin was independent of changes in body weight, body mass index, glucose control, insulin resistance, and plasma insulin. In conclusion, treatment with pioglitazone is associated with a decrease in preprandial ghrelin levels and therefore, the weight gain and increased food intake related to pioglitazone use cannot be explained by its effects on ghrelin. The effect of pioglitazone on ghrelin is independent of changes in body weight, body mass index, plasma insulin, insulin resistance, or glucose control.

  20. Direct inhibitory effects of pioglitazone on hepatic fetuin-A expression.

    Science.gov (United States)

    Ochi, Akinobu; Mori, Katsuhito; Emoto, Masanori; Nakatani, Shinya; Morioka, Tomoaki; Motoyama, Koka; Fukumoto, Shinya; Imanishi, Yasuo; Koyama, Hidenori; Ishimura, Eiji; Inaba, Masaaki

    2014-01-01

    Fetuin-A, a circulating glycoprotein synthesized in the liver, is involved in insulin resistance and type 2 diabetes. However, regulation of fetuin-A synthesis has remained obscure. We previously reported that pioglitazone treatment significantly reduced serum fetuin-A levels in patients with type 2 diabetes. To clarify whether pioglitazone can directory inhibit hepatic fetuin-A synthesis, we investigated the effects of pioglitazone on fetuin-A expression both in vitro and in vivo. Pioglitazone treatment suppressed mRNA and protein expression of fetuin-A in Fao hepatoma cells. Interestingly, rosiglitazone but not metformin, also inhibited fetuin-A expression. In addition, GW 9662, an inhibitor of peroxisome proliferator-activated receptor (PPAR) γ, reversed pioglitazone-induced suppression of fetuin-A, suggesting that thiazolidinedione derivatives may have common characteristics with regard to fetuin-A suppression, possibly through PPARγactivation. Finally, oral administration of pioglitazone to mice for 8 weeks resulted in suppression of hepatic fetuin-A mRNA. These findings suggest that pioglitazone may partially ameliorate insulin resistance through its direct inhibitory effects on fetuin-A expression in the liver.

  1. Effect of creatine and pioglitazone on Hk-2 cell line cisplatin nephrotoxicity.

    Science.gov (United States)

    Genc, Gurkan; Kilinc, Veli; Bedir, Abdulkerim; Ozkaya, Ozan

    2014-08-01

    Cisplatin is a chemotherapeutic agent, which is used in the treatment of various solid organ cancers, and its main dose limiting side effect of cisplatin is nephrotoxicity. The aim of this study is to investigate the role of pioglitazone and creatine on cisplatin nephrotoxicity in vitro. Real-time cell analyzer system (RTCA) was used for real-time and time-dependent analysis of the cellular response of HK-2 cells following incubation with cisplatin and combination with creatine or pioglitazone hydrochloride. First, half-maximal inhibitory concentrations (IC50) of cisplatin, creatine and pioglitazone were calculated by RTCA system. Afterwards creatine and pioglitazone was administered with serial dilutions under RTCA system. IC50 dose for cisplatin was 7.69 M × 10(-5) at 24th hour and 3.93 M × 10(-6) at 48th hour. IC50 dose for pioglitazone was 1.61 M × 10(-3) at 24th hour and 2.85 M × 10(-4) at 48th hour. Although cells were treated the dose of 40,225 mM creatine, IC50 dose could not been reached. Neither pioglitazone nor creatine had additional protective effect in any dose. Consequently, beneficial effect of creatine and pioglitazone on cisplatin-induced cell death could not be found. Further studies and clinical trials are needed to evaluate the effect of different doses of these drugs in cisplatin-induced nephrotoxicity.

  2. Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo.

    Science.gov (United States)

    Bogacka, Iwona; Xie, Hui; Bray, George A; Smith, Steven R

    2005-05-01

    Thiazolidenediones such as pioglitazone improve insulin sensitivity in diabetic patients by several mechanisms, including increased uptake and metabolism of free fatty acids in adipose tissue. The purpose of the present study was to determine the effect of pioglitazone on mitochondrial biogenesis and expression of genes involved in fatty acid oxidation in subcutaneous fat. Patients with type 2 diabetes were randomly divided into two groups and treated with placebo or pioglitazone (45 mg/day) for 12 weeks. Mitochondrial DNA copy number and expression of genes involved in mitochondrial biogenesis were quantified by real-time PCR. Pioglitazone treatment significantly increased mitochondrial copy number and expression of factors involved in mitochondrial biogenesis, including peroxisome proliferator-activated receptor (PPAR)-gamma coactivator-1alpha and mitochondrial transcription factor A. Treatment with pioglitazone stimulated the expression of genes in the fatty acid oxidation pathway, including carnitine palmitoyltransferase-1, malonyl-CoA decarboxylase, and medium-chain acyl-CoA dehydrogenase. The expression of PPAR-alpha, a transcriptional regulator of genes encoding mitochondrial enzymes involved in fatty acid oxidation, was higher after pioglitazone treatment. Finally, the increased mitochondrial copy number and the higher expression of genes involved in fatty acid oxidation in human adipocytes may contribute to the hypolipidemic effects of pioglitazone.

  3. Pioglitazone and the risk of bladder cancer: An Indian retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Sunil Gupta

    2015-01-01

    Full Text Available Aim: To determine whether pioglitazone is associated with an increased risk of bladder cancer among Indian type 2 diabetic patients. Methods: A retrospective data analysis of 2222 type 2 diabetic patients was conducted. The study subjects were divided into two equal groups: 1111 pioglitazone users and 1111 pioglitazone non-users. The safety of pioglitazone therapy was analyzed in terms of occurrence of bladder and other types of cancers along with its efficacy in terms of glycemic control. Parameters for assessing safety were duration of disease, duration of usage and total dose of pioglitazone consumed across age groups, glycemic control, obesity and family history of any cancer. Bladder cancer prevalence was analyzed on the basis of urinary cytology, urine routine and microscopy, hematuria, urinary nuclear matrix protein 22 analysis and ultrasonography. Results: Of the 2222 cases analysed, there was no evidence of bladder cancer in any of the studied groups, (p=not significant which was also evident among 1111 patients on Pioglitazone therapy with a cumulative dose consumption of 2737 mg to 1,31,400 mg. On subgroup analysis, there was no evidence of bladder cancer amongst patients with age >60 years, duration of diabetes > 10 years and uncontrolled diabetics (HbA1c >8% with cumulative pioglitazone consumption of >28,000 mg. A significant number of patients achieved good glycemic control (HbA1c <7.5% with pioglitazone therapy. Conclusion: Pioglitazone therapy was not associated with occurrence of bladder cancer among Indian type 2 diabetic patients and demonstrated good glycemic control.

  4. The bioflavonoid quercetin synergises with PPAR-γ agonist pioglitazone in reducing angiotensin-II contractile effect in fructose-streptozotocin induced diabetic rats.

    Science.gov (United States)

    Kunasegaran, Thubasni; Mustafa, Mohd Rais; Murugan, Dharmani Devi; Achike, Francis I

    2016-06-01

    This study investigated the effects of combined minimal concentrations of quercetin and pioglitazone on angiotensin II-induced contraction of the aorta from fructose-streptozotocin (F-STZ)-induced type 2 diabetic rats and the possible role of superoxide anions (O2(-)) and nitric oxide (NO) in their potential therapeutic interaction. Contractile responses to Ang II of aortic rings from Sprague-Dawley (SD) and F-STZ rats were tested following pre-incubation of the tissues in the vehicle (DMSO; 0.05%), quercetin (Q, 0.1 μM), pioglitazone (P, 0.1 μM) or their combination (P + Q; 0.1 μM each). The amount of superoxide anion was evaluated by lucigenin-enhanced chemiluminescence and dihydroethidium fluorescence, and NO by assay of total nitrate/nitrite, and 4-Amino-5-Methylamino-2',7'-Difluorofluorescein (DAF-FM) diacetate. The synergistic reduction of Ang II-induced contraction of diabetic but not normal aorta with minimally effective concentrations of P + Q occurs through inhibiting O2(-) and increasing NO bioavailability. This finding opens the possibility of maximal vascular protective/antidiabetic effects with low dose pioglitazone combined with quercetin, thus minimizing the risk of adverse effects.

  5. Acquired portosystemic collaterals: anatomy and imaging*

    Science.gov (United States)

    Leite, Andréa Farias de Melo; Mota Jr., Américo; Chagas-Neto, Francisco Abaeté; Teixeira, Sara Reis; Elias Junior, Jorge; Muglia, Valdair Francisco

    2016-01-01

    Portosystemic shunts are enlarged vessels that form collateral pathological pathways between the splanchnic circulation and the systemic circulation. Although their causes are multifactorial, portosystemic shunts all have one mechanism in common-increased portal venous pressure, which diverts the blood flow from the gastrointestinal tract to the systemic circulation. Congenital and acquired collateral pathways have both been described in the literature. The aim of this pictorial essay was to discuss the distinct anatomic and imaging features of portosystemic shunts, as well as to provide a robust method of differentiating between acquired portosystemic shunts and similar pathologies, through the use of illustrations and schematic drawings. Imaging of portosystemic shunts provides subclinical markers of increased portal venous pressure. Therefore, radiologists play a crucial role in the identification of portosystemic shunts. Early detection of portosystemic shunts can allow ample time to perform endovascular shunt operations, which can relieve portal hypertension and prevent acute or chronic complications in at-risk patient populations. PMID:27777479

  6. Acquired portosystemic collaterals: anatomy and imaging

    Energy Technology Data Exchange (ETDEWEB)

    Leite, Andrea Farias de Melo; Mota Junior, Americo, E-mail: andreafariasm@gmail.com [Instituto de Medicina Integral Professor Fernando Figueira de Pernambuco (IMIP), Recife, PE (Brazil); Chagas-Neto, Francisco Abaete [Universidade de Fortaleza (UNIFOR), Fortaleza, CE (Brazil); Teixeira, Sara Reis; Elias Junior, Jorge; Muglia, Valdair Francisco [Universidade de Sao Paulo (FMRP/USP), Ribeirao Preto, SP (Brazil). Faculdade de Medicina

    2016-07-15

    Portosystemic shunts are enlarged vessels that form collateral pathological pathways between the splanchnic circulation and the systemic circulation. Although their causes are multifactorial, portosystemic shunts all have one mechanism in common - increased portal venous pressure, which diverts the blood flow from the gastrointestinal tract to the systemic circulation. Congenital and acquired collateral pathways have both been described in the literature. The aim of this pictorial essay was to discuss the distinct anatomic and imaging features of portosystemic shunts, as well as to provide a robust method of differentiating between acquired portosystemic shunts and similar pathologies, through the use of illustrations and schematic drawings. Imaging of portosystemic shunts provides subclinical markers of increased portal venous pressure. Therefore, radiologists play a crucial role in the identification of portosystemic shunts. Early detection of portosystemic shunts can allow ample time to perform endovascular shunt operations, which can relieve portal hypertension and prevent acute or chronic complications in at-risk patient populations. (author)

  7. Pioglitazone Randomised Italian Study on Metabolic Syndrome (PRISMA): effect of pioglitazone with metformin on HDL-C levels in Type 2 diabetic patients.

    Science.gov (United States)

    Genovese, S; Passaro, A; Brunetti, P; Comaschi, M; Cucinotta, D; Egan, C G; Chinea, B; Bravi, F; Di Pietro, C

    2013-09-01

    Previous evidence indicates that pioglitazone may improve dyslipidemia in patients with Type 2 diabetes mellitus (T2DM). The primary objective of this study was to evaluate the effect of either pioglitazone or placebo with metformin on levels of serum HDL cholesterol (HDL-C) in patients with T2DM. A secondary objective evaluated changes in metabolic syndrome (MS)-specific parameters. This multicenter, double-blind, randomized study was performed in patients with T2DM treated with metformin and hemoglobin A1c (HbA1c) levels between 6-8%, central obesity and reduced HDL-C. MS was evaluated from global changes in parameter values and expressed as a single factorial score following multivariate analysis of each parameter. 213 patients (110 in the pioglitazone group and 103 in the placebo group) were available for intention-to-treat analysis. Pioglitazone-treated patients showed a significant increase in HDL-C compared to placebo group (6.3 mg/dl vs 3.0 mg/dl; pHDL-C and the reduction of insulin resistance and atherogenic LDL subfractions), support findings from the PROactive trial, where pioglitazone showed pleiotropic effects and reduced death, fatal myocardial infarction (MI) and non-fatal MI in T2DM patients with MS. Furthermore, medication used in this study showed good tolerability.

  8. Pioglitazone-induced congestive heart failure and pulmonary edema in a patient with preserved ejection fraction.

    Science.gov (United States)

    Jearath, Vaneet; Vashisht, Rajan; Rustagi, Vipul; Raina, Sujeet; Sharma, Rajesh

    2016-01-01

    Pioglitazone-induced heart failure is known in patients with underlying heart disease, but is not well documented in patients with normal left ventricular function. Pioglitazone has been very popular as it is an insulin sensitizer and insulin resistance is prevalent among Indians. Fluid retention exacerbates pre-existing heart failure or precipitates heart failure in a patient with underlying left ventricular dysfunction. However, pathogenesis of heart failure in a patient with normal left ventricular function is not known. Probably it is due to dose-related effect on pulmonary endothelial permeability, rather than alterations in left ventricular mass or ejection fraction. We report a patient who developed congestive heart failure and pulmonary edema with normal left ventricular function within 1 year of starting pioglitazone therapy. We have to be careful in monitoring all possible side effects during followup when patients are on pioglitazone therapy.

  9. Pioglitazone-induced congestive heart failure and pulmonary edema in a patient with preserved ejection fraction

    Science.gov (United States)

    Jearath, Vaneet; Vashisht, Rajan; Rustagi, Vipul; Raina, Sujeet; Sharma, Rajesh

    2016-01-01

    Pioglitazone-induced heart failure is known in patients with underlying heart disease, but is not well documented in patients with normal left ventricular function. Pioglitazone has been very popular as it is an insulin sensitizer and insulin resistance is prevalent among Indians. Fluid retention exacerbates pre-existing heart failure or precipitates heart failure in a patient with underlying left ventricular dysfunction. However, pathogenesis of heart failure in a patient with normal left ventricular function is not known. Probably it is due to dose-related effect on pulmonary endothelial permeability, rather than alterations in left ventricular mass or ejection fraction. We report a patient who developed congestive heart failure and pulmonary edema with normal left ventricular function within 1 year of starting pioglitazone therapy. We have to be careful in monitoring all possible side effects during followup when patients are on pioglitazone therapy. PMID:27127397

  10. Pioglitazone treatment increases spontaneous growth hormone (GH) secretion and stimulated GH levels in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Støving, René Klinkby; Hagen, Claus

    2005-01-01

    and improved insulin sensitivity during pioglitazone treatment may affect GH secretion. OBJECTIVE: The objective of the study was to investigate the effect of pioglitazone on GH levels in PCOS. DESIGN: Thirty insulin-resistant PCOS patients were randomized to either 16 wk pioglitazone (30 mg/d) or placebo...... treatment. Before and after intervention, levels of fasting insulin, GH, total IGF-I, free IGF-I, IGF binding protein-1, IGF-II, free fatty acids, testosterone, and SHBG were measured. Patients underwent whole-body dual x-ray absorptiometry scans, pyridostigmine-GHRH tests, and 24-h 20-min integrated blood...... sampling for measurement of GH. RESULTS: Peak GH and area under the curve for GH in pyridostigmine-GHRH tests and 24-h mean GH concentrations and pulsatile GH secretion significantly increased after pioglitazone treatment. No significant changes were observed in GH pulse frequency, pulse duration...

  11. Pioglitazone-induced congestive heart failure and pulmonary edema in a patient with preserved ejection fraction

    Directory of Open Access Journals (Sweden)

    Vaneet Jearath

    2016-01-01

    Full Text Available Pioglitazone-induced heart failure is known in patients with underlying heart disease, but is not well documented in patients with normal left ventricular function. Pioglitazone has been very popular as it is an insulin sensitizer and insulin resistance is prevalent among Indians. Fluid retention exacerbates pre-existing heart failure or precipitates heart failure in a patient with underlying left ventricular dysfunction. However, pathogenesis of heart failure in a patient with normal left ventricular function is not known. Probably it is due to dose-related effect on pulmonary endothelial permeability, rather than alterations in left ventricular mass or ejection fraction. We report a patient who developed congestive heart failure and pulmonary edema with normal left ventricular function within 1 year of starting pioglitazone therapy. We have to be careful in monitoring all possible side effects during followup when patients are on pioglitazone therapy.

  12. Dynamics of collateral circulation in progressive asymptomatic carotid disease.

    Science.gov (United States)

    Moll, F L; Eikelboom, B C; Vermeulen, F E; van Lier, H J; Schulte, B P

    1986-03-01

    Inadequacy of collateral arterial flow is the major risk factor for hemispheric infarction in association with spontaneous occlusion of the ipsilateral carotid artery. This prospective study was designed to measure the adaptation of collateral cerebral circulation through the circle of Willis in patients in whom a unilateral carotid stenosis of hemodynamic consequence develops asymptomatically. The collateral cerebral potential is assessed by ocular pneumoplethysmography (OPG) during proximal common carotid artery compression, measuring the collateral ophthalmic artery pressure (COAP). During an average follow-up of almost 3 years (maximum more than 7 years), 45 patients showed asymptomatic development of a unilateral hemodynamically significant carotid stenosis according to OPG evidence. In these patients the mean index COAP/brachial artery pressure did not change on the side of stenosis progression (p greater than 0.05). The developed carotid stenosis had only reduced collateral circulation to the contralateral hemisphere. The risk of inadequate collateral cerebral circulation remained during progression of asymptomatic extracranial arterial obstructive disease.

  13. Pioglitazone (Actos) and bladder cancer: Legal system triumphs over the evidence.

    Science.gov (United States)

    Davidson, Mayer B

    2016-08-01

    In preclinical studies, pioglitazone was associated with bladder cancer in male rats (but not in female rats, mice dogs or monkeys). Because of this association, the Federal Drug Administration requested a large 10year epidemiological study to evaluate whether there was an association between bladder cancer and exposure to pioglitazone in patients. A 5-year interim report published in 2011 showed no significant association between ever vs never exposure to the drug but a significant association in patients exposed to pioglitazone for >2years. Importantly, the final 10year report did not confirm the 5year interim report finding no association between bladder cancer and pioglitazone, even after >4years of exposure to the drug. However, as would be expected, following the 5-year interim report, many epidemiological studies were carried out and civil litigation lawsuits began to be filed. Of the 23 epidemiological studies that have been published to date, 18 showed no association between bladder cancer and pioglitazone (5 with a combination of rosiglitazone and pioglitazone). Of the five that did show a significant association with pioglitazone, three could not be confirmed in the same population and in one of them there were significantly more risk factors for bladder cancer in the patients exposed to pioglitazone. In the fourth one, a significant association became non-significant when patients >79years were included. In the fifth one, detection bias was a major flaw. Currently, >11,000 legal cases have been filed, many of which claim emotional distress due to the fear of bladder cancer. To limit their legal costs, the pharmaceutical company has established a 2.4 billion dollar settlement pool. So much for evidence-based medicine.

  14. Long-term pioglitazone therapy improves arterial stiffness in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Harashima, Keiichiro; Hayashi, Junichi; Miwa, Takashi; Tsunoda, Tooru

    2009-06-01

    Pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, not only improves insulin resistance and glycemic control, but may also have additional beneficial vascular effects in patients with type 2 diabetes mellitus. We investigated whether pioglitazone had an influence on arterial stiffness, which is an independent predictor of cardiovascular events, in 204 patients with type 2 diabetes mellitus. A prospective, nonrandomized, open-label trial was performed that involved 41 patients treated with pioglitazone, 46 patients receiving sulfonylureas, 67 patients on insulin, and 50 patients on diet/exercise only. The follow-up period was 56 +/- 3 months. Arterial stiffness was evaluated by using the arterial stiffness index (ASI), which was based on analysis of the pulse wave amplitude pattern obtained during automated blood pressure measurement in the upper limb. The 4 groups had a similar baseline ASI, which was greater than the reference range in each group. Although antidiabetic therapies improved hemoglobin A(1c) and low-density lipoprotein cholesterol, ASI only decreased significantly in the pioglitazone group. Thus, pioglitazone improved abnormal arterial stiffness in patients with type 2 diabetes mellitus via a mechanism beyond the metabolic improvement. These findings may have important clinical implications in the use of pioglitazone in patients with type 2 diabetes mellitus.

  15. The association of pioglitazone and urinary tract disease in type 2 diabetic Taiwanese: bladder cancer and chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Mei-Yueh Lee

    Full Text Available OBJECTIVE: Although studies have shown an association between pioglitazone and bladder cancer, the associated factors have not been identified. The aim of this study was to investigate the factors that may link pioglitazone to bladder cancer. MATERIALS AND METHODS: In total, 34,970 study subjects were identified from the National Health Insurance Research Database in 2003 with follow-up from 2005 to 2009. The demographic characteristics of patients who had used and had never used pioglitazone, including age, sex, diabetes duration, urinary tract disease, nephropathy, bladder cancer, and cumulative dose and duration of pioglitazone therapy, were analyzed using the χ2 test. Cox proportional hazard regression models were used to determine the independent effects of pioglitazone on bladder cancer and newly developed chronic kidney disease. RESULTS: Among 3,497 ever users and 31,473 never users of pioglitazone, the respective incident cases of bladder cancer were 12 (0.4% and 72 (0.2%, and for newly developed chronic kidney disease 245 (8.1% and 663 (2.3%, respectively. Ever use of pioglitazone [1.59(1.32-1.91], cumulative dose of pioglitazone 10,500 mg [1.34 (1.04-1.73], and duration of therapy 12 months [1.39 (1.09-1.76] were associated with the development of chronic kidney disease. CONCLUSIONS: There was no association of pioglitazone use with bladder cancer development, however, there was an association with an increased risk of newly developed chronic kidney disease.

  16. Mortgage Finance and Security of Collateral

    DEFF Research Database (Denmark)

    Haldrup, Karin

    2011-01-01

    Developing economies face a gigantic lack of financing for urbanization due to the absence of formal and transparent property markets. The paper discuss the interference between mortgage finance and collateral security by using the Danish mortgage financing model as an example, because of its 200...... years long history, and because the system is recommended as an option in emerging markets and as a possible model for remedying failures in mature housing finance markets. It is suggested that development policies in land administration need to be revised in order to support a widening of credit...

  17. Transvenous closure of large aortopulmonary collateral

    Directory of Open Access Journals (Sweden)

    Parag W Barwad

    2014-01-01

    Full Text Available Aortopulmonary collaterals (APCs are occluded either preoperatively or at the time of cardiac surgery in patients with pulmonary atresia and ventricular septal defect (PAVSD. If left untreated, APCs are an important cause of deterioration in the early postoperative period. We present here an unusual case with a large residual APC causing refractory low-output state in the early postoperative period. Usual arterial approach failed due to extensive angulation with ostial narrowing. The large residual APC was successfully closed with an Amplatzer duct occluder (ADO device delivered through the transvenous route.

  18. Financing with Receivables: Factoring, Securitization and Collateral

    Directory of Open Access Journals (Sweden)

    Ioana Benea

    2013-11-01

    Full Text Available Short term financing is vital for the financial survival of any company, because very often they are facing deficits of cash during their activity. Therefore a company has to identify the optimal solutions in order to cover those (temporary deficits. A good solution to this problem is the financing with receivables using factoring, securitization and collateral. In this paper we try to analyze how this types of financing works and which are their advantages and costs. Also, we developed a reasoning pattern in order to evaluate the best receivables financing alternative for the Romanian companies.

  19. 12 CFR 614.4250 - Collateral evaluation standards.

    Science.gov (United States)

    2010-01-01

    ... and procedures. Such a collateral evaluation shall be identified as either a collateral valuation or a...) Potential liabilities, including those associated with any hazardous waste or other environmental concerns... requested minimum valuation or specific valuation or approval of a loan. (b) For purposes of...

  20. IRT parameter estimation with response times as collateral information

    NARCIS (Netherlands)

    Linden, W.J. van der; RKlein Entink, R.H.; Fox, J.-P.

    2010-01-01

    Hierarchical modeling of responses and response times on test items facilitates the use of response times as collateral information in the estimation of the response parameters. In addition to the regular information in the response data, two sources of collateral information are identified: (a) the

  1. Collateral Informant Assessment in Alcohol Use Research Involving College Students

    Science.gov (United States)

    Hagman, Brett T.; Cohn, Amy M.; Noel, Nora E.; Clifford, Patrick R.

    2010-01-01

    Objective: This study examined the associations between college students' self-reported alcohol use and corresponding collateral reports and identified factors that influence agreement between both sets of reports. Participants/Methods: Subject-collateral pairs (N = 300) were recruited from undergraduate psychology courses. Results: Data yielded…

  2. Effects of pioglitazone and fenofibrate co-administration on bone biomechanics and histomorphometry in ovariectomized rats.

    Science.gov (United States)

    Smith, Susan Y; Samadfam, Rana; Chouinard, Luc; Awori, Malaika; Bénardeau, Agnes; Bauss, Frieder; Guldberg, Robert E; Sebokova, Elena; Wright, Matthew B

    2015-11-01

    Pioglitazone, the peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist is an effective therapy for type 2 diabetes, but has been associated with increased risk for bone fracture. Preclinical studies suggest that PPAR-α agonists (e.g., fenofibrate) increase bone mineral density/content, although clinical data on bone effects of fibrates are lacking. We investigated the effects of pioglitazone (10 mg/kg/day) and fenofibrate (25 mg/kg/day) on bone strength and bone histomorphometric parameters in osteopenic ovariectomized (OVX) rats. An additional group of rats received a combination of pioglitazone + fenofibrate to mimic the effects of a dual PPAR-α/γ agonist. The study consisted of a 13-week treatment phase followed by a 6-week treatment-free recovery period. Pioglitazone significantly reduced biomechanical strength at the lumbar spine and femoral neck compared with rats administered fenofibrate. Co-treatment with pioglitazone + fenofibrate had no significant effect on bone strength in comparison with OVX vehicle controls. Histomorphometric analysis of the proximal tibia revealed that pioglitazone suppressed bone formation and increased bone resorption at both cancellous and cortical bone sites relative to OVX vehicle controls. In contrast, fenofibrate did not affect bone resorption and only slightly suppressed bone formation. Discontinuation of pioglitazone treatment, both in the monotherapy and in the combination therapy arms, resulted in restoration of bone formation and resorption rates, demonstrating reversibility of effects. The above data support the concept that dual activation of PPAR-γ and PPAR-α attenuates the negative effects of PPAR-γ agonism on bone strength.

  3. Beneficial effects of pioglitazone on retardation of persistent atrial fibrillation progression in diabetes mellitus patients.

    Science.gov (United States)

    Liu, Bing; Wang, Jiancheng; Wang, Guoxing

    2014-01-01

    This study aimed to explore the effects of pioglitazone treatment on progression from persistent atrial fibrillation (AF) to permanent atrial fibrillation in diabetes mellitus (DM) patients and to investigate the possible mechanisms involved in those effects.A total of 146 diabetes mellitus (DM) patients with firstly identified persistent AF were selected. Seventy patients were randomized into the pioglitazone (30 mg/day) group and 76 into the placebo group. Pro-collagen type I carboxyterminal peptide (PICP), advanced glycation end products (AGEs), and angiotensin II were assayed and left atrial diameter (LA diameter) was measured at the first presence of persistent AF, and at 6 and 14 months of follow-up. The time point of identification of permanent AF and the incidence of permanent AF in the patients were all recorded.Thirty-seven (49%) of the 76 patients in the placebo group and 21 (30%) of the 70 patients in the pioglitazone group progressed to permanent AF (P = 0.028). No significant differences existed in the follow-up time (20.5 ± 3.97 months for pioglitazone group versus 20.9 ± 4.14 months for placebo group) between the two groups (P = 0.535). In the pioglitazone group, no significant change was found in angiotensin II level. The PICP level did not change significantly at 6-months of follow-up, but decreased significantly at 14-months of follow-up (P = 0.032). The AGE (P = 0.037 at 6-month follow-up, P pioglitazone treatment may decrease the incidence of permanent AF in DM patients with persistent AF, which may be associated with the suppressing effect of pioglitazone on AGEs.

  4. Effect of low dose pioglitazone on glycemic control and insulin resistance in Type 2 diabetes: A randomized, double blind, clinical trial.

    Science.gov (United States)

    Rajagopalan, Sujit; Dutta, Pinaki; Hota, Debasish; Bhansali, Anil; Srinivasan, Anand; Chakrabarti, Amitava

    2015-09-01

    This study shows that pioglitazone 7.5 mg/day as an add-on therapy in Southeast Asian patients with Type 2 diabetes is safer and equally efficacious as the 15- and 30-mg doses of pioglitazone. Hence it is prudent to start pioglitazone therapy at a lower dose of 7.5 mg/day.

  5. The Enhanced Driver’s License: Collateral Gains or Collateral Damage?

    Science.gov (United States)

    2012-12-01

    95 Advancements in recent decades have reduced the size and cost of RFID technology and as such, have increased the number of purposes ( supply ... chain management, tracking livestock, controlling building access) to include access control for the border.96 The first recorded use RFID technology...purpose of storing the biometric facial image capture—quality images 180 " Samsung Announces High

  6. Beneficial effects of canagliflozin in combination with pioglitazone on insulin sensitivity in rodent models of obese type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Yoshinori Watanabe

    Full Text Available Despite its insulin sensitizing effects, pioglitazone may induce weight gain leading to an increased risk of development of insulin resistance. A novel sodium glucose co-transporter 2 (SGLT2 inhibitor, canagliflozin, provides not only glycemic control but also body weight reduction through an insulin-independent mechanism. The aim of this study was to investigate the combined effects of these agents on body weight control and insulin sensitivity.Effects of combination therapy with canagliflozin and pioglitazone were evaluated in established diabetic KK-Ay mice and prediabetic Zucker diabetic fatty (ZDF rats.In the KK-Ay mice, the combination therapy further improved glycemic control compared with canagliflozin or pioglitazone monotherapy. Furthermore, the combination significantly attenuated body weight and fat gain induced by pioglitazone and improved hyperinsulinemia. In the ZDF rats, early intervention with pioglitazone monotherapy almost completely prevented the progressive development of hyperglycemia, and no further improvement was observed by add-on treatment with canagliflozin. However, the combination significantly reduced pioglitazone-induced weight gain and adiposity and improved the Matsuda index, suggesting improved whole-body insulin sensitivity.Our study indicates that combination therapy with canagliflozin and pioglitazone improves insulin sensitivity partly by preventing glucotoxicity and, at least partly, by attenuating pioglitazone-induced body weight gain in two different obese diabetic animal models. This combination therapy may prove to be a valuable option for the treatment and prevention of obese type 2 diabetes.

  7. Beneficial effects of canagliflozin in combination with pioglitazone on insulin sensitivity in rodent models of obese type 2 diabetes.

    Science.gov (United States)

    Watanabe, Yoshinori; Nakayama, Keiko; Taniuchi, Nobuhiko; Horai, Yasushi; Kuriyama, Chiaki; Ueta, Kiichiro; Arakawa, Kenji; Senbonmatsu, Takaaki; Shiotani, Masaharu

    2015-01-01

    Despite its insulin sensitizing effects, pioglitazone may induce weight gain leading to an increased risk of development of insulin resistance. A novel sodium glucose co-transporter 2 (SGLT2) inhibitor, canagliflozin, provides not only glycemic control but also body weight reduction through an insulin-independent mechanism. The aim of this study was to investigate the combined effects of these agents on body weight control and insulin sensitivity. Effects of combination therapy with canagliflozin and pioglitazone were evaluated in established diabetic KK-Ay mice and prediabetic Zucker diabetic fatty (ZDF) rats. In the KK-Ay mice, the combination therapy further improved glycemic control compared with canagliflozin or pioglitazone monotherapy. Furthermore, the combination significantly attenuated body weight and fat gain induced by pioglitazone and improved hyperinsulinemia. In the ZDF rats, early intervention with pioglitazone monotherapy almost completely prevented the progressive development of hyperglycemia, and no further improvement was observed by add-on treatment with canagliflozin. However, the combination significantly reduced pioglitazone-induced weight gain and adiposity and improved the Matsuda index, suggesting improved whole-body insulin sensitivity. Our study indicates that combination therapy with canagliflozin and pioglitazone improves insulin sensitivity partly by preventing glucotoxicity and, at least partly, by attenuating pioglitazone-induced body weight gain in two different obese diabetic animal models. This combination therapy may prove to be a valuable option for the treatment and prevention of obese type 2 diabetes.

  8. Beneficial Effects of Canagliflozin in Combination with Pioglitazone on Insulin Sensitivity in Rodent Models of Obese Type 2 Diabetes

    Science.gov (United States)

    Watanabe, Yoshinori; Nakayama, Keiko; Taniuchi, Nobuhiko; Horai, Yasushi; Kuriyama, Chiaki; Ueta, Kiichiro; Arakawa, Kenji; Senbonmatsu, Takaaki; Shiotani, Masaharu

    2015-01-01

    Background Despite its insulin sensitizing effects, pioglitazone may induce weight gain leading to an increased risk of development of insulin resistance. A novel sodium glucose co-transporter 2 (SGLT2) inhibitor, canagliflozin, provides not only glycemic control but also body weight reduction through an insulin-independent mechanism. The aim of this study was to investigate the combined effects of these agents on body weight control and insulin sensitivity. Methods Effects of combination therapy with canagliflozin and pioglitazone were evaluated in established diabetic KK-Ay mice and prediabetic Zucker diabetic fatty (ZDF) rats. Results In the KK-Ay mice, the combination therapy further improved glycemic control compared with canagliflozin or pioglitazone monotherapy. Furthermore, the combination significantly attenuated body weight and fat gain induced by pioglitazone and improved hyperinsulinemia. In the ZDF rats, early intervention with pioglitazone monotherapy almost completely prevented the progressive development of hyperglycemia, and no further improvement was observed by add-on treatment with canagliflozin. However, the combination significantly reduced pioglitazone-induced weight gain and adiposity and improved the Matsuda index, suggesting improved whole-body insulin sensitivity. Conclusions Our study indicates that combination therapy with canagliflozin and pioglitazone improves insulin sensitivity partly by preventing glucotoxicity and, at least partly, by attenuating pioglitazone-induced body weight gain in two different obese diabetic animal models. This combination therapy may prove to be a valuable option for the treatment and prevention of obese type 2 diabetes. PMID:25615826

  9. Pioglitazone Lowers Serum Retinol Binding Protein 4 by Suppressing its Expression in Adipose Tissue of Obese Rats

    Directory of Open Access Journals (Sweden)

    Chaoyu Zhu

    2015-01-01

    Full Text Available Background/Aims: Pioglitazone, a peroxisome proliferator-activated receptor γ activator, is clinically used to treat insulin resistance. However, the underlying mechanism of pioglitazone's action remains unclear. We investigated whether, and how, pioglitazone modulates serum level of retinol binding protein 4 (RBP4, an adipocytokine associated with obesity and insulin resistance. Methods: Insulin sensitivity was determined by oral glucose tolerance test, and RBP4 expression was detected by RT-PCR and Western blotting. Results: Pioglitazone treatment significantly decreased serum RBP4 levels in obese rats, which was correlated with reduced body weight and increased insulin sensitivity. Moreover, pioglitazone greatly decreased RBP4 mRNA and protein levels in adipose tissue but not in the liver. Consistently, pioglitazone treatment significantly reduced RBP4 protein expression in 3T3-L1 adipocytes but not in HepG2 cells. Conclusion: These results demonstrate that pioglitazone inhibits the level of serum RPB4 by suppressing RBP4 expression in adipose tissue of obese rats, suggesting that inhibiting RBP4 expression in adipocytes may provide a mechanism by which pioglitazone improves insulin sensitivity in insulin-resistant subjects.

  10. Protective effect of pioglitazone on kidney injury in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Xiao-Hui Peng; Pei-Yu Liang; Shan-Ji Ou; Xiong-Bing Zu

    2014-01-01

    Objective:To investigate the protective effect of pioglitazone on kidney injury in diabetic rat model and its mechanisms.Methods:Forty healthySpragueDawley rats were selected and randomly divided into five groups, with8 rats in each group.GroupA served as control group and were administered with sterile citrate buffer(i.p.) as placebo.GroupsB,C,D andE rats were injected(i.p.) with streptozotocin to induce typeⅠdiabetes.Diabetic rats inGroupB were intragastrically administered with sterile saline solution alone.GroupsC,D andE rats were intragastrically given pioglitazone hydrochloride suspension at doses of10,20,30 mg/kg per day, respectively.After eight weeks of treatment, all rats were anesthetized and blood was withdrawn from the abdominal aortic for detection of hemoglobinA1c, serum creatinine(SCr) and blood urea nitrogen(BUN) levels.Rats were then sacrificed and the left kidney was excised for calculation of kidney hypertrophy index(KHI), observation of renal pathological changes using light microscope and electron microscope.Mean glomerular cross-sectional areas(MGA), mean glomerular volume (MGV), glomerular basement membrane thickness and foot process fusion ratio were calculated. RT-PCR was employed for detection of podocalyxin(PCX) protein expression.Results:Results showed that levels of hemoglobinA1c,BUN,SCr inGroupsB,C,D andE rats were significantly higher than those inGroupA(P<0.05), whileBUN andSCr levels in rats ofGroupsC,D andE were significantly lower than those inGroupB(P<0.05).KHI,MGA andMGV levels were significantly higher inGroupsB,C,D andE rats than those inGroupA(P<0.05);KHI andMGA levels inGroup B rats were significantly higher than those inGroupsC,D andE(P<0.05) andMGV inGroups D andE was significantly lower than that inGroupsB andC(P<0.05).Histology study showed normal glomerulus structure, morphology, volume, endothelial cells and mesangial cells as well as clear glomerular capillary inGroupA rats.Renal mesangial matrix proliferation and

  11. Pentoxifylline and melatonin in combination with pioglitazone ameliorate experimental non-alcoholic fatty liver disease.

    Science.gov (United States)

    Zaitone, Sawsan; Hassan, Neven; El-Orabi, Naglaa; El-Awady, El-Sayed

    2011-07-15

    Insulin resistance, oxidative stress and cytokine imbalance are key pathophysiological mechanisms in non-alcoholic fatty liver disease (NAFLD). This study aimed at evaluating the effect of treatment with the insulin sensitizer, pioglitazone, the tumor necrosis factor-α inhibitor, pentoxifylline, and the antioxidant, melatonin and their combinations in rats with NAFLD. Rats were fed a high-fat diet (HFD) for eight weeks to induce NAFLD. For an additional eight weeks, rats were fed the HFD along with pioglitazone, pentoxifylline, melatonin alone or in combination. Liver index and insulin resistance index were calculated. Serum liver enzyme activities, total cholesterol, triglycerides and tumor necrosis factor-α (TNF-α) were determined. Tissue triglycerides, malondialdehyde and reduced glutathione were measured and liver injury was evaluated by histopathological examination. HFD induced severe hepatic steatosis, inflammation and fibrosis. In addition, liver index, insulin resistance index, activities of liver enzymes and serum level of total cholesterol, triglycerides and TNF-α were elevated. This was coupled with an increase in tissue triglycerides, malondialdehyde and depletion of reduced glutathione. Pioglitazone, pentoxifylline and melatonin, alone or in combination; reduced the insulin resistance index, activities of liver enzymes, hepatic malondialdehyde and increased hepatic reduced glutathione level. Pentoxifylline led to a decrease in serum TNF-α level, however, pioglitazone and melatonin reduced serum total cholesterol and triglycerides. In conclusion, data in this study indicate that pentoxifylline and melatonin can be used as promising adjuvant therapies to pioglitazone in the clinical management of NAFLD.

  12. Pioglitazone Suppresses CXCR7 Expression To Inhibit Human Macrophage Chemotaxis through Peroxisome Proliferator-Activated Receptor γ.

    Science.gov (United States)

    Zhao, Duo; Zhu, Zhicheng; Li, Dan; Xu, Rihao; Wang, Tiance; Liu, Kexiang

    2015-11-17

    Cardiovascular disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Pioglitazone, the widely used thiazolidinedione, is shown to be efficient in the prevention of cardiovascular complications of T2DM. In this study, we report that pioglitazone inhibits CXCR7 expression and thus blocks chemotaxis in differentiated macrophage without perturbing cell viability or macrophage differentiation. In addition, pioglitazone-mediated CXCR7 suppression and chemotaxis inhibition occur via activating peroxisome proliferator-activated receptor γ (PPARγ) but not PPARα in differentiated macrophage. More importantly, pioglitazone therapy-induced PPARγ activation suppresses CXCR7 expression in human carotid atherosclerotic lesions. Collectively, our data demonstrate that pioglitazone suppresses CXCR7 expression to inhibit human macrophage chemotaxis through PPARγ.

  13. Effects of red mold dioscorea with pioglitazone, a potentially functional food, in the treatment of diabetes

    Directory of Open Access Journals (Sweden)

    Chien-Li Chen

    2015-12-01

    Full Text Available The prevalence of type 2 diabetes mellitus is increasing rapidly, and its treatment with pioglitazone is likely to induce rhabdomyolysis. We aimed to determine the effect of cotreatment with pioglitazone and red mold dioscorea (RMD produced by Monascus purpureus NTU 568 on pancreas function in streptozotocin (STZ-induced diabetic rats. In diabetic rats fed RMD, RMD with pioglitazone, and pioglitazone alone, insulin concentrations increased significantly by 18.6–40.4%, 64.0–100.0%, and 52.8%, respectively, compared with that in the diabetic group (p < 0.05. Oral glucose tolerance was impaired in the STZ-induced diabetic group within 4 weeks, however, oral glucose tolerance in rats treated with RMD or RMD with pioglitazone improved after 4 weeks, 6 weeks, and 8 weeks. Findings from this study might lend support to the use of RMD as a novel functional food for the prevention of diabetes.

  14. Collateral lessons from recent acute ischemic stroke trials.

    Science.gov (United States)

    Liebeskind, David S

    2014-05-01

    Numerous acute ischemic stroke trials have recently published detailed results, providing an opportunity to consider the role of collaterals in stroke pathophysiology and their influential effect on patient outcomes. Safety and Efficacy of NeuroFlo Technology in Ischemic Stroke (SENTIS), the largest randomized controlled trial of device therapy to date, tested the potential augmentation of collateral perfusion. SYNTHESIS Expansion, Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE), and Interventional Management of Stroke (IMS) III chronicled the saga of endovascular therapy trialed against medical treatment for acute ischemic stroke. These recent randomized studies, however, largely neglect current device technology available for endovascular therapy as advanced by the TREVO2 and SOLITAIRE™(TM) FR With the Intention For Thrombectomy (SWIFT) studies. Such exhaustive efforts in recent trials have failed to introduce a new treatment for stroke that unequivocally improves patient outcomes. Collateral perfusion is widely recognized to vary across individuals in any population and exerts a dramatic effect on baseline variables including the time course of ischemic injury, stroke severity, imaging findings, and therapeutic opportunities. Similarly, collaterals have been recognized to influence recanalization, reperfusion, hemorrhagic transformation, and subsequent neurological outcomes after stroke. Collateral lessons may be gleaned from these trials, to expand consideration of overall study results and perhaps most importantly, alter ongoing and new trials in development. Detailed analyses of available information on collaterals from these trials demonstrate that collaterals may be more influential than the choice of treatment modality or intervention.

  15. Morphological patterns of the collateral sulcus in the human brain.

    Science.gov (United States)

    Huntgeburth, Sonja C; Petrides, Michael

    2012-04-01

    The collateral sulcal complex is an important landmark on the medial surface of the temporal lobe. Anteriorly, it delineates the limbic regions of the parahippocampal gyrus from the visual-processing areas of the fusiform gyrus. Posteriorly, it continues into the occipital lobe, bearing no relationship to the memory-related limbic regions. Given the considerable extent of the sulcus and functional heterogeneity of the surrounding cortex, an investigation of the morphology of this sulcus was carried out to examine whether it is continuous or a series of sulcal parts, i.e. independent sulci classified together under the name collateral sulcus. We investigated the collateral sulcal complex using magnetic resonance images taking into account the three-dimensional nature of the brain. Our examination demonstrated three separate sulcal segments: (i) an anterior segment, the rhinal sulcus, delineating the uncus from the adjacent temporal neocortex, (ii) a middle segment, the collateral sulcus proper, forming the lateral border of the posterior parahippocampal cortex, and (iii) a caudal segment, the occipital extent of the collateral sulcus, within the occipital lobe. Three relationships exist between the rhinal sulcus and collateral sulcus proper, only one being clearly identifiable from the surface. Posteriorly, the collateral sulcus proper and the occipital collateral sulcus, although appearing continuous on the brain surface, can be separated in the depth of the sulcus in all cases. These results provide quantification of the location and variability within standard stereotaxic space for the three collateral sulcus segments that could be used to aid accurate identification of functional activation peaks derived from neuroimaging studies.

  16. Transarterial chemoembolization through collateral vessels in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Hye; Han, Joon Koo; Chung, Jin Wook; Park, Jae Hyung; Han, Man Chung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1993-11-15

    We performed 70 procedures of transarterial chemoembolization (TAE) through extrahepatic collateral vessels (n=27) or parasitic feeders (n=18) in 45 hepatocellular carcinoma patients. The collaterals developed after interruption of the hepatic artery due to repeated TAE (n=17), surgical ligation (n=7)and primary celiac occlusion (n=3). Radiologic findings suggest the existence of parasitic or collateral supply for hepatocellular carcinoma were 1) a focal defect of Lipiodol retention on CT or plain film after TAE via the hepatic artery, 2) dilated and tortuous vessels around the mass on angiography, 3) persistent elevation of the level of serum alpha-fetoprotein or continuous clinical symptoms in spite of sufficient devascularization of the tumor via the hepatic artery, and 4) radiological findings of direct invasion into adjacent organ. The sites of the catheter placement were the inferior phrenic artery(n=19), omental branches(n=16), periportal collaterals (n=6), pancreaticodenal arcade (n=3), gastroduodenal artery(n=3), internal mammary artery (n=2), intercosal artery (n=2), lateral thoracic artery (n=1), bronchial artery (n=1), and colic branches (n=1). Masses feeded by the inferior phrenic and chest wall collaterals were usually located at the dome area of the liver, and the omental and gastroduodenal collaterals developed in the masses located at the inferior tip of the liver. After TAE via collateral vessels, 37 patients underwent follow-up study. In 18 cases(48%), the tumor favorably responded to TAE. Specific complications of collateral TAE were epigastric soreness (n=10), severe shoulder pain (n=4), and embolization of the spinal artery during embolization through the intercostal artery (n=1). In conclusion, various extrahepatic collateals are important alternative or addition routes for effective chemoembolization in patients with advanced hepatoma, and early recognition of the parasitic supply and the effort to perform TAE via collaterals is very

  17. Pioglitazone improves the cardio-ankle vascular index in patients with type 2 diabetes mellitus treated with metformin

    Directory of Open Access Journals (Sweden)

    Ohira M

    2014-07-01

    Full Text Available Masahiro Ohira,1 Takashi Yamaguchi,1 Atsuhito Saiki,1 Noriko Ban,1 Hidetoshi Kawana,1 Ayako Nagumo,1 Takeyoshi Murano,2 Kohji Shirai,3 Ichiro Tatsuno1 1Center for Diabetes, Endocrinology and Metabolism, 2Department of Clinical Laboratory Medicine, 3Department of Vascular Function, Sakura Hospital, Toho University Medical Center, Chiba, Japan Background: Type 2 diabetes is known to be associated with elevated cardiovascular mortality. Pioglitazone improves blood pressure (BP and pulse wave velocity (PWV, which is an arterial stiffness parameter. Arterial stiffness is closely associated with cardiovascular disease. However, PWV is correlated with BP. The cardio-ankle vascular index (CAVI reflects arterial stiffness independent of BP. Pioglitazone improves PWV but reduces blood pressure. The aim of this study was to re-evaluate the effect of pioglitazone on arterial stiffness with CAVI. Methods: Sixty patients with type 2 diabetes mellitus and already on 500 mg/day of metformin received add-on therapy of pioglitazone 15 mg/day or glimepiride 1 mg/day for 6 months, during which time changes in their metabolic parameters and CAVI were observed. Results: After 6 months of treatment, both pioglitazone (n=30 and glimepiride (n=30 improved fasting blood glucose and glycated hemoglobin. The changes in fasting blood glucose and glycated hemoglobin between the two groups were greater in the pioglitazone group. Systolic and diastolic BP was decreased in both groups, with no significant between-group differences. Only pioglitazone increased serum adiponectin levels, and the change in adiponectin between the pioglitazone and glimepiride groups was significantly different. CAVI was decreased significantly by pioglitazone but remained unchanged after treatment with glimepiride. The change in CAVI between the two groups was significantly different. Conclusion: These results suggest that pioglitazone improves CAVI, a BP-independent arterial stiffness parameter

  18. Pioglitazone ameliorates the lowered exercise capacity and impaired mitochondrial function of the skeletal muscle in type 2 diabetic mice.

    Science.gov (United States)

    Takada, Shingo; Hirabayashi, Kagami; Kinugawa, Shintaro; Yokota, Takashi; Matsushima, Shouji; Suga, Tadashi; Kadoguchi, Tomoyasu; Fukushima, Arata; Homma, Tsuneaki; Mizushima, Wataru; Masaki, Yoshihiro; Furihata, Takaaki; Katsuyama, Ryoichi; Okita, Koichi; Tsutsui, Hiroyuki

    2014-10-05

    We have reported that exercise capacity is reduced in high fat diet (HFD)-induced diabetic mice, and that this reduction is associated with impaired mitochondrial function in skeletal muscle (SKM). However, it remains to be clarified whether the treatment of diabetes ameliorates the reduced exercise capacity. Therefore, we examined whether an insulin-sensitizing drug, pioglitazone, could improve exercise capacity in HFD mice. C57BL/6J mice were fed a normal diet (ND) or HFD, then treated with or without pioglitazone (3 mg/kg/day) to yield the following 4 groups: ND+vehicle, ND+pioglitazone, HFD+vehicle, and HFD+pioglitazone (n=10 each). After 8 weeks, body weight, plasma glucose, and insulin in the HFD+vehicle were significantly increased compared to the ND+vehicle group. Pioglitazone normalized the insulin levels in HFD-fed mice, but did not affect the body weight or plasma glucose. Exercise capacity determined by treadmill tests was significantly reduced in the HFD+vehicle, and this reduction was almost completely ameliorated in HFD+pioglitazone mice. ADP-dependent mitochondrial respiration, complex I and III activities, and citrate synthase activity were significantly decreased in the SKM of the HFD+vehicle animals, and these decreases were also attenuated by pioglitazone. NAD(P)H oxidase activity was significantly increased in the HFD+vehicle compared with the ND+vehicle, and this increase was ameliorated in HFD+pioglitazone mice. Pioglitazone improved the exercise capacity in diabetic mice, which was due to the improvement in mitochondrial function and attenuation of oxidative stress in the SKM. Our data suggest that pioglitazone may be useful as an agent for the treatment of diabetes mellitus.

  19. Pulmonary artery agenesis associated with coronary collaterals among adults.

    Science.gov (United States)

    Darwazah, Ahmad K; Alhaddad, Imad A

    2016-07-16

    Unilateral agenesis of the pulmonary artery is a rare congenital anomaly, which commonly involves the right side. Cases are associated with systemic collaterals, that may also rarely arise from the coronary arteries.Two adult patients are presented with a right pulmonary artery agenesis associated with collaterals from the right coronary artery. The implications of such an anomaly on pulmonary artery pressure and lung pathology differs among both cases. The association of coronary collaterals is rare and its implication is variable among various patients.

  20. Prevention of diabetes with pioglitazone in ACT NOW: physiologic correlates.

    Science.gov (United States)

    Defronzo, Ralph A; Tripathy, Devjit; Schwenke, Dawn C; Banerji, Maryann; Bray, George A; Buchanan, Thomas A; Clement, Stephen C; Gastaldelli, Amalia; Henry, Robert R; Kitabchi, Abbas E; Mudaliar, Sunder; Ratner, Robert E; Stentz, Frankie B; Musi, Nicolas; Reaven, Peter D

    2013-11-01

    We examined the metabolic characteristics that attend the development of type 2 diabetes (T2DM) in 441 impaired glucose tolerance (IGT) subjects who participated in the ACT NOW Study and had complete end-of-study metabolic measurements. Subjects were randomized to receive pioglitazone (PGZ; 45 mg/day) or placebo and were observed for a median of 2.4 years. Indices of insulin sensitivity (Matsuda index [MI]), insulin secretion (IS)/insulin resistance (IR; ΔI0-120/ΔG0-120, ΔIS rate [ISR]0-120/ΔG0-120), and β-cell function (ΔI/ΔG × MI and ΔISR/ΔG × MI) were calculated from plasma glucose, insulin, and C-peptide concentrations during oral glucose tolerance tests at baseline and study end. Diabetes developed in 45 placebo-treated vs. 15 PGZ-treated subjects (odds ratio [OR] 0.28 [95% CI 0.15-0.49]; P IGT > T2DM) was associated with improvements in insulin sensitivity (OR 0.61 [95% CI 0.54-0.80]), IS (OR 0.61 [95% CI 0.50-0.75]), and β-cell function (ln IS/IR index and ln ISR/IR index) (OR 0.26 [95% CI 0.19-0.37]; all P < 0.0001). Of the factors measured, improved β-cell function was most closely associated with final glucose tolerance status.

  1. Effects of Collateral Pledges in Reducing Credit Risks - Confronting Banks in Jordan, as Lending Institutions

    Directory of Open Access Journals (Sweden)

    Dr. Ahmad Z.  Siam

    2007-01-01

    Full Text Available he research aims at investigating the effects of Collaterals pledges in reducing credit Risks .To achieve research goals data were collected from all commercial banks operating in Jordan. Research concluded that banks in Jordan use collaterals effectively and in a wide range, and collaterals size have a direct impact on credit risk. Credit risk differs with collaterals.

  2. 13 CFR 120.1850 - Will the Collateral be held by SBA?

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Will the Collateral be held by SBA... Loan Program) § 120.1850 Will the Collateral be held by SBA? Yes, SBA or its expressly authorized agent... all Collateral for SISMBD Loans in a custodial account. Certificates held as Collateral must be...

  3. Protective Effects of Vildagliptin against Pioglitazone-Induced Bone Loss in Type 2 Diabetic Rats

    Science.gov (United States)

    Kwak, Kyung Min; Kim, Ju-Young; Yu, Seung Hee; Lee, Sihoon; Kim, Yeun Sun; Park, Ie Byung; Kim, Kwang-Won; Lee, Kiyoung

    2016-01-01

    Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model. We randomly divided 12-week-old male Zucker Diabetic Fatty (ZDF) rats into four groups; control, vildagliptin, pioglitazone, and vildagliptin and pioglitazone combination. Animals in each group received the respective treatments for 5 weeks. We performed an intraperitoneal glucose tolerance test (IPGTT) before and after treatment. BMD and the trabecular micro-architecture were measured by DEXA and micro CT, respectively, at the end of the treatment. The circulating levels of active GLP-1, bone turnover markers, and sclerostin were assayed. Vildagliptin treatment significantly increased BMD and trabecular bone volume. The combination therapy restored BMD, trabecular bone volume, and trabecular bone thickness that were decreased by pioglitazone. The levels of the bone formation marker, osteocalcin, decreased and that of the bone resorption marker, tartrate-resistant acid phosphatase (TRAP) 5b increased in the pioglitazone group. These biomarkers were ameliorated and the pioglitazone-induced increase in sclerostin level was lowered to control values by the addition of vildagliptin. In conclusion, our results indicate that orally administered vildagliptin demonstrated a protective effect on pioglitazone-induced bone loss in a type 2 diabetic rat model. PMID:27997588

  4. Effects of pioglitazone on serum leptin and adiponectin in polycystic ovary syndrome patients with insulin resistance

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To investigate the effects of pioglitazone on serum leptin and adiponectin in polycystic ovary syndrome(PCOS)patients with insulin resistance(IR).Methods Thirty-five PCOS patients with IR were treated with pioglitazone 15mg/d for 12 weeks.The results of ovulation induction were observed.The changes of fasting plasma glucose(FPG),fasting serum insulin(FINS),serum levels of leptin,adiponectin,follicle-stimulating hormone(FSH),luteinizing hormone(LH),testosterone(T)and blood fat were examined at the ...

  5. Effect of pioglitazone on glucose metabolism and luteinizing hormone secretion in women with polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Hermann, Anne Pernille; Andersen, Marianne

    2006-01-01

    OBJECTIVE: To thoroughly examine the mechanisms for insulin resistance in polycystic ovary syndrome (PCOS) and to evaluate the effects of pioglitazone treatment on insulin resistance, beta-cell function, LH secretion, and glucose metabolism. DESIGN: Randomized, blinded, placebo-controlled study....... SETTING: Outpatient clinic, at a university hospital in Denmark. PATIENT(S): Thirty obese women with PCOS and 14 weight-matched healthy females. INTERVENTION(S): Sixteen weeks of blinded treatment with pioglitazone (30 mg/d) or placebo. MAIN OUTCOME MEASURE(S): Fasting blood samples, 24-hour 20-minute...

  6. Intracranial pressure elevation reduces flow through collateral vessels and the penetrating arterioles they supply. A possible explanation for 'collateral failure' and infarct expansion after ischemic stroke.

    Science.gov (United States)

    Beard, Daniel J; McLeod, Damian D; Logan, Caitlin L; Murtha, Lucy A; Imtiaz, Mohammad S; van Helden, Dirk F; Spratt, Neil J

    2015-05-01

    Recent human imaging studies indicate that reduced blood flow through pial collateral vessels ('collateral failure') is associated with late infarct expansion despite stable arterial occlusion. The cause for 'collateral failure' is unknown. We recently showed that intracranial pressure (ICP) rises dramatically but transiently 24 hours after even minor experimental stroke. We hypothesized that ICP elevation would reduce collateral blood flow. First, we investigated the regulation of flow through collateral vessels and the penetrating arterioles arising from them during stroke reperfusion. Wistar rats were subjected to intraluminal middle cerebral artery (MCA) occlusion (MCAo). Individual pial collateral and associated penetrating arteriole blood flow was quantified using fluorescent microspheres. Baseline bidirectional flow changed to MCA-directed flow and increased by >450% immediately after MCAo. Collateral diameter changed minimally. Second, we determined the effect of ICP elevation on collateral and watershed penetrating arteriole flow. Intracranial pressure was artificially raised in stepwise increments during MCAo. The ICP increase was strongly correlated with collateral and penetrating arteriole flow reductions. Changes in collateral flow post-stroke appear to be primarily driven by the pressure drop across the collateral vessel, not vessel diameter. The ICP elevation reduces cerebral perfusion pressure and collateral flow, and is the possible explanation for 'collateral failure' in stroke-in-progression.

  7. Pricing a Collateralized Derivative Trade with a Funding Value Adjustment

    Directory of Open Access Journals (Sweden)

    Chadd B. Hunzinger

    2015-01-01

    Full Text Available The 2008 credit crisis changed the manner in which derivative trades are conducted. One of these changes is the posting of collateral in a trade to mitigate the counterparty credit risk. Another is the realization that banks are not risk-free and, as a result, cannot borrow at the risk-free rate any longer. The latter led banks to introduced the controversial adjustment to derivative prices, known as a funding value adjustment (FVA, which is interlinked with the posting of collateral. In this paper, we extend the Cox, Ross and Rubinstein (CRR discrete-time model to include collateral and FVA. We prove that this derived model is a discrete analogue of Piterbarg’s partial differential equation (PDE, which describes the price of a collateralized derivative. The fact that the two models coincide is also verified by numerical implementation of the results that we obtain.

  8. Pioglitazone attenuates the severity of sodium taurocholate-induced severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Ping Xu; Xiao-Jiang Zhou; Ling-Quan Chen; Jiang Chen; Yong Xie; Long-Hua Lv; Xiao-Hua Hou

    2007-01-01

    AIM: To determine the effect of pioglitazone, a specific peroxisome proliferator-activated receptor-γ (PPARγ)ligand, on development of severe acute pancreatitis (SAP) and expression of nuclear factor-kappa B (NF-κB)and intercellular adhesion molecule-1 (ICAM-1) in the pancreas.METHODS: Male Sprague-Dawley (SD) rats (160-200 g)were randomly allocated into three groups (n = 18in each group): severe acute pancreatitis group,pioglitazone group, sham group. SAP was induced by retrograde infusion of 1 mL/kg body weight 5% sodium taurocholate (STC) into the biliopancreatic duct of male SD rats. Pioglitazone was injected intraperitoneally two hours piror to STC infusion. Blood and ascites were obtained for detecting amylase and ascitic capacity. Pancreatic wet/dry weight ratio, expression of NF-κB and ICAM-1 in pancreatic tissues were detected by immunohistochemical staining. Pancreatic tissue samples were stained with hematoxylin and eosin (HE)for routine optic microscopy.RESULTS: Sham group displayed normal pancreatic structure. SAP group showed diffuse hemorrhage,necrosis and severe edema in focal areas of pancreas.There was obvious adipo-saponification in abdominal cavity. Characteristics such as pancreatic hemorrhage,necrosis, severe edema and adipo-saponification were found in pioglitazone group, but the levels of those injuries were lower in pioglitazone group than those in SAP group. The wet/dry pancreatic weight ratio,ascetic capacity, serum and ascitic activities of anylase in the SAP group were significantly higher than those in the sham group and pioglitazone group respectively (6969.50 ± 1368.99 vs 2104.67 ± 377.16, 3.99 ± 1.22 vs 2.48 ± 0.74, P < 0.01 or P < 0.05). According to Kusske criteria, the pancreatic histologic score showed that interstitial edema, inflammatory infiltration,parenchyma necrosis and parenchyma hommorrhage in SAP group significantly differed from those in the sham group and pioglitazone group (7.17 ± 1.83 vs 0.50 ±0.55, 7

  9. A randomized, double blind, placebo-controlled trial of pioglitazone in combination with riluzole in amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Luc Dupuis

    Full Text Available BACKGROUND: Pioglitazone, an oral anti-diabetic that stimulates the PPAR-gamma transcription factor, increased survival of mice with amyotrophic lateral sclerosis (ALS. METHODS/PRINCIPAL FINDINGS: We performed a phase II, double blind, multicentre, placebo controlled trial of pioglitazone in ALS patients under riluzole. 219 patients were randomly assigned to receive 45 mg/day of pioglitazone or placebo (one: one allocation ratio. The primary endpoint was survival. Secondary endpoints included incidence of non-invasive ventilation and tracheotomy, and slopes of ALS-FRS, slow vital capacity, and quality of life as assessed using EUROQoL EQ-5D. The study was conducted under a two-stage group sequential test, allowing to stop for futility or superiority after interim analysis. Shortly after interim analysis, 30 patients under pioglitazone and 24 patients under placebo had died. The trial was stopped for futility; the hazard ratio for primary endpoint was 1.21 (95% CI: 0.71-2.07, p = 0.48. Secondary endpoints were not modified by pioglitazone treatment. Pioglitazone was well tolerated. CONCLUSION/SIGNIFICANCE: Pioglitazone has no beneficial effects on the survival of ALS patients as add-on therapy to riluzole. TRIAL REGISTRATION: Clinicaltrials.gov NCT00690118.

  10. Pioglitazone prescription increases risk of bladder cancer in patients with type 2 diabetes: an updated meta-analysis.

    Science.gov (United States)

    He, Shiyao; Tang, Yu-hong; Zhao, Guobin; Yang, Xiaolong; Wang, Dehou; Zhang, Ye

    2014-03-01

    Pioglitazone is widely used for glycemic control in patients with type 2 diabetes mellitus, but evidence regarding the association between pioglitazone and bladder cancer risk is confusing. A systematic search of databases was carried out, and other relevant papers were also identified. Then, the analyses were conducted according to the PRISMA and MOOSE guidelines. After quality assessment, nine datasets from 10 available studies were included on the basis of inclusion criteria. The incidence of bladder cancer among pioglitazone ever users and never users, pooled from four cohort and one randomized studies, were 84.51 and 66.68 per 100,000 person-years, respectively. Nine studies representing 2,596,856 diabetic patients were recognized as eligible for overall study; the result suggested an increased risk of bladder cancer in patients exposed to pioglitazone. A persistent significance was detected after being adjusted by age, gender, and use of other diabetes medications. Subgroup analyses indicated that the significantly increased incidence of bladder cancer was found in men, but not in women. Additionally, the analyses addressing increasing exposure to pioglitazone observed a dose-response relation between exclusive ever use of pioglitazone and bladder cancer in terms of cumulative duration of use and cumulative dosage. With some limitations, our results suggest an increased risk of bladder cancer in diabetic patients using pioglitazone, especially for men with long-term and high-dose exposure. Additional studies are needed to provide more precise evidences to support our results.

  11. Pioglitazone treatment reduces adipose tissue inflammation through reduction of mast cell and macrophage number and by improving vascularity.

    Directory of Open Access Journals (Sweden)

    Michael Spencer

    Full Text Available Adipose tissue in insulin resistant subjects contains inflammatory cells and extracellular matrix components. This study examined adipose pathology of insulin resistant subjects who were treated with pioglitazone or fish oil.Adipose biopsies were examined from nine insulin resistant subjects before/after treatment with pioglitazone 45 mg/day for 12 weeks and also from 19 subjects who were treated with fish oil (1,860 mg EPA, 1,500 mg DHA daily. These studies were performed in a clinical research center setting.Pioglitazone treatment increased the cross-sectional area of adipocytes by 18% (p = 0.01, and also increased capillary density without affecting larger vessels. Pioglitazone treatment decreased total adipose macrophage number by 26%, with a 56% decrease in M1 macrophages and an increase in M2 macrophages. Mast cells were more abundant in obese versus lean subjects, and were decreased from 24 to 13 cells/mm(2 (p = 0.02 in patients treated with pioglitazone, but not in subjects treated with FO. Although there were no changes in total collagen protein, pioglitazone increased the amount of elastin protein in adipose by 6-fold.The PPARγ agonist pioglitazone increased adipocyte size yet improved other features of adipose, increasing capillary number and reducing mast cells and inflammatory macrophages. The increase in elastin may better permit adipocyte expansion without triggering cell necrosis and an inflammatory reaction.

  12. A comparison of glycemic control, water retention, and musculoskeletal effects of balaglitazone and pioglitazone in diet-induced obese rats

    DEFF Research Database (Denmark)

    Henriksen, Kim; Byrjalsen, Inger; Nielsen, Rasmus H

    2009-01-01

    : vehicle, pioglitazone 10 mg/kg, pioglitazone 30 mg/kg, balaglitazone 5 mg/kg, balaglitazone 10 mg/kg. At day -7, 21 and 42 fasting serum samples were collected and whole body tissue composition was evaluated by MR scanning. Food intake and bodyweights were monitored during the study period. At day 42...... of equipotent glucose lowering concentrations of the partial PPARgamma agonist balaglitazone and the full agonist pioglitazone in male diet-induced obese rats, to investigate effects on bone formation, fluid retention and fat accumulation. Sixty male dio induced obese rats were divided into five categories...

  13. Plasma osteoprotegerin is associated with testosterone levels but unaffected by pioglitazone treatment in patients with polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Glintborg, D; Hermann, Pernille; Rasmussen, Lars Melholt;

    2013-01-01

    Objective Increased osteoprotegerin (OPG) levels are associated with increased cardiovascular risk and decreased bone resorption. Pioglitazone treatment reduces the inflammatory state but may decrease bone mineral density. OPG levels during pioglitazone treatment have not previously been evaluated...... in polycystic ovary syndrome (PCOS). Research design and methods Plasma OPG levels were measured in 30 PCOS patients before and after randomized treatment with 30 mg pioglitazone/placebo for 16 weeks. Fourteen age and BMI matched healthy women were included as controls. Clinical and hormonal evaluations...

  14. PPAR-γ agonist pioglitazone affects rat gouty arthritis by regulating cytokines.

    Science.gov (United States)

    Wang, R-C; Jiang, D-M

    2014-08-28

    The objective was to study peroxisome proliferator-activated receptor gamma (PPARγ) agonist pioglitazone regulation effect and its mechanism of expression of cytokines on acute gouty arthritis synovial in rats. Rats with unilateral ankle were injected with artificial monosodium urate (MSU) crystals to make the acute gouty arthritis model. Taking the synovium 48 h after the injection of MSU and using RT-PCR, we assessed the effect of pioglitazone (20 mg·kg(-1)·day(-1), oral administration) on synovial expression, by detecting tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interferon-γ (IFN-γ). The pioglitazone treatment group showed synovial expression of TNF-α, and IFN-γ was significantly lower than in the control group; the inhibition rates were 78.5 and 60.4%. The IL-1 expression difference was not statistically significant between the two groups. Pioglitazone has anti-inflammatory effects on acute gouty arthritis by inhibiting the expression of TNF-α and IFN-γ.

  15. Pioglitazone treatment restores in vivo muscle oxidative capacity in a rat model of diabetes

    NARCIS (Netherlands)

    Wessels, B.; Ciapaite, J.; van den Broek, N. M. A.; Houten, S. M.; Nicolay, K.; Prompers, J. J.

    2015-01-01

    Aim: To determine the effect of pioglitazone treatment on in vivo and ex vivo muscle mitochondrial function in a rat model of diabetes. Methods: Both the lean, healthy rats and the obese, diabetic rats are Zucker Diabetic Fatty (ZDF) rats. The homozygous fa/fa ZDF rats are obese and diabetic. The he

  16. Effect of pioglitazone on the abrogated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart

    Directory of Open Access Journals (Sweden)

    Dhiraj Mittal

    2016-01-01

    Conclusion: Cardioprotective effect of IPC gets lost in hyperlipidemic rat heart. The results suggest that perfusion of pioglitazone restored the cardioprotective effect of IPC in hyperlipidemic rat heart, an effect that may be via PI3K and mTOR.

  17. Efficacy and safety of colesevelam in combination with pioglitazone in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Rosenstock, J; Truitt, K E; Baz-Hecht, M; Ford, D M; Tao, B; Chou, H S

    2014-12-01

    Colesevelam improves glycemic control in patients with type 2 diabetes when added to existing metformin-, sulfonylurea-, or insulin-based regimens. We evaluated colesevelam's effects in subjects on stable pioglitazone-based therapy. This 24-week multicenter, double-blind, randomized, placebo-controlled study enrolled adults with type 2 diabetes who had suboptimal glycemic control [HbA1c ≥ 58 mmol/mol (7.5%) and ≤ 80 mmol/mol (9.5%)] on pioglitazone (30 or 45 mg) with or without 1-2 other oral antidiabetes medications. Subjects were randomized to colesevelam 3.8 g/day (n = 280) or placebo (n = 282) added to existing pioglitazone-based therapy. Primary efficacy variable was mean change in HbA1c from baseline to Week 24. Secondary variables included safety and tolerability, fasting plasma glucose changes, glycemic responses, and lipid profile. Tertiary variables included lipid particle profile changes by nuclear magnetic resonance. Colesevelam decreased HbA1c [least-squares mean treatment difference, - 3.5 mmol/mol (- 0.32%); p diabetes inadequately controlled with pioglitazone-based therapy, add-on colesevelam therapy improved glycemic control and lipid parameters and was well tolerated. ClinicalTrials.gov identifier: NCT00789750.

  18. Combination of Vildagliptin and Pioglitazone in Experimental Type 2 Diabetes in Male Rats.

    Science.gov (United States)

    Refaat, Rowaida; Sakr, Ahmed; Salama, Mona; El Sarha, Ashgan

    2016-09-01

    Preclinical Research The majority of studies on vildagliptin and pioglitazone have focused on their combination in glycemic control. The aim of the present study was to investigate their effects in combination on (i) hyperglycemia-induced oxidative stress and inflammation and (ii) on organs involved in the pathophysiology of diabetes, pancreas, kidney and liver. Type 2 diabetes was induced using low-dose streptozotocin in male Wistar rats. Diabetic rats were treated for 4 weeks, with vildagliptin (10 mg/kg/day), pioglitazone (10 mg/kg/day) and their combination. Diabetic rats showed elevated fasting serum glucose, fasting serum insulin, serum transaminases together with a deleterious lipid profile and elevated serum creatinine and urea concentrations. Serum levels of the inflammatory markers tumor necrosis factor-α (TNF-α) and nitrite/nitrate were also elevated compared to normal rats. Oxidative stress was manifested by lowered hepatic reduced glutathione (GSH) and increased malondialdehyde (MDA) levels. Pancreatic sections from diabetic rats showed degenerated islets with poorly maintained architecture that was prevented by drug treatment. Pioglitazone was generally more effective than vildagliptin in the studied parameters except for the lipid profile where the effect of both drugs was comparable and for the liver enzymes and renal parameters where vildagliptin was more effective. The combination of vildagliptin and pioglitazone produced superior effects than either drug alone. Drug Dev Res 77 : 251-257, 2016. © 2016 Wiley Periodicals, Inc.

  19. 'Wellbeing': a collateral casualty of modernity?

    Science.gov (United States)

    Carlisle, Sandra; Henderson, Gregor; Hanlon, Phil W

    2009-11-01

    In the now vast empirical and theoretical literature on wellbeing knowledge of the subject is provided mainly by psychology and economics, where understanding of the concept are framed in very different ways. We briefly rehearse these, before turning to some important critical points which can be made about this burgeoning research industry, including the tight connections between the meanings of the concept with the moral value systems of particular 'modern' societies. We then argue that both the 'science' of wellbeing and its critique are, despite their diversity, re-connected by and subsumed within the emerging environmental critique of modern consumer society. This places concerns for individual and social wellbeing within the broader context of global human problems and planetary wellbeing. A growing number of thinkers now suggest that Western society and culture are dominated by materialistic and individualistic values, made manifest at the political and social levels through the unending pursuit of economic growth, and at the individual level by the seemingly endless quest for consumer goods, regardless of global implications such as broader environmental harms. The escalating growth of such values is associated with a growing sense of individual alienation, social fragmentation and civic disengagement and with the decline of more spiritual, moral and ethical aspects of life. Taken together, these multiple discourses suggest that wellbeing can be understood as a collateral casualty of the economic, social and cultural changes associated with late modernity. However, increasing concerns for the environment have the potential to counter some of these trends, and in so doing could also contribute to our wellbeing as individuals and as social beings in a finite world.

  20. Evaluation of exposure to pioglitazone and risk of prostate cancer: a nested case–control study

    Science.gov (United States)

    Boxall, Naomi; Bennett, Dimitri; Hunger, Matthias; Dolin, Paul; Thompson, Paula L

    2016-01-01

    Objectives Investigate potential association between pioglitazone exposure and risk of prostate cancer. Research design and methods Nested, matched case–control study. UK primary care data (Clinical Practice Research Datalink (CPRD) GOLD) linked to inpatient (Hospital Episode Statistics (HES)) and cancer registry (National Cancer Information Network (NCIN)) data. English men aged ≥40 years diagnosed with type 2 diabetes mellitus, January 1, 2001 to January 5, 2015. Cases, with prostate cancer diagnosis, matched with up to 4 controls by age, cohort entry date and region. ORs for association of exposure to pioglitazone to incident prostate cancer, adjusted for potential confounders. Results From a cohort of 47 772 men with 243 923 person-years follow-up, 756 definite cases of prostate cancer were identified. Incidence was 309.9/100 000 person-years (95% CI 288.6 to 332.8). Pioglitazone use was not associated with prostate cancer risk; adjusted OR 0.759, 95% CI 0.502 to 1.148. Analyses showed no difference when possible cases, prostate cancer in CPRD GOLD only, included (adjusted OR 0.726, 95% CI 0.510 to 1.034). No association when adjusted for channeling bias (OR 0.778, 95% CI 0.511 to 1.184) or limited to an index date prior to July 1, 2011 (adjusted OR 0.508, 95% CI 0.294 to 0.879), despite prostate-specific antigen screening occurring more frequently among cases than controls (81.6% of 756 definite cases cf. 24.2% of 2942 controls (ppioglitazone use, increasing pioglitazone dose or increasing time since initiation. Conclusions In this real-world, nested matched case–control study, exposure to pioglitazone was not associated with increased risk of prostate cancer. PMID:28074141

  1. Comparison clinical and metabolic effects of metformin and pioglitazone in polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Karoon Shahebrahimi

    2016-01-01

    Full Text Available Introduction: Polycystic ovary syndrome (PCOS is one of the most common endocrine disorders in women. PCOS comprises a broad spectrum of anomalies, including hyperandrogenism, chronic anovulation, obesity, and infertility. Insulin resistance and its compensatory hyperinsulinemia play a key role in the pathogenicity of PCOS. This study compares the effects of 2 types of insulin sensitizer drugs, metformin and pioglitazone, on clinical, metabolic, and endocrine characteristics of women with PCOS. Methods: In this randomized clinical trial, 56 women with PCOS (ages 20–49 years were treated orally with either metformin (500 mg 3 times daily or pioglitazone (30 mg daily for 3 months. Clinical (body weight, blood pressure [BP], and body mass index and laboratory indices (fasting blood sugar [FBS], serum triglyceride [TG], cholesterol, low-density lipoprotein, high-density lipoprotein, insulin, testosterone, and dehydroepiandrosterone [DHEA] were measured before and after therapy. Data were analyzed by Chi-square and McNemar's tests. Results: Significant decreases were seen after treatment with metformin in extent of hair loss (P = 0.008, wrist circle (P = 0.011, weight (P = 0.047, diastolic BP (P = 0.023, and DHEA (P = 0.035. A significant decrease in TG was seen with pioglitazone treatment (P = 0.047. In both groups, significant decreases in acne, menstrual disturbance, FBS, and serum insulin were seen. Conclusion: There is a significant amelioration of endocrine and metabolic indices with pioglitazone in PCOS patients. Although we were not able to recommend one treatment regime over the other, pioglitazone offers a useful, alternate treatment in women with PCOS who are not able to tolerate metformin.

  2. Comparison clinical and metabolic effects of metformin and pioglitazone in polycystic ovary syndrome

    Science.gov (United States)

    Shahebrahimi, Karoon; Jalilian, Nasrin; Bazgir, Nasrin; Rezaei, Mansour

    2016-01-01

    Introduction: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. PCOS comprises a broad spectrum of anomalies, including hyperandrogenism, chronic anovulation, obesity, and infertility. Insulin resistance and its compensatory hyperinsulinemia play a key role in the pathogenicity of PCOS. This study compares the effects of 2 types of insulin sensitizer drugs, metformin and pioglitazone, on clinical, metabolic, and endocrine characteristics of women with PCOS. Methods: In this randomized clinical trial, 56 women with PCOS (ages 20–49 years) were treated orally with either metformin (500 mg 3 times daily) or pioglitazone (30 mg daily) for 3 months. Clinical (body weight, blood pressure [BP], and body mass index) and laboratory indices (fasting blood sugar [FBS], serum triglyceride [TG], cholesterol, low-density lipoprotein, high-density lipoprotein, insulin, testosterone, and dehydroepiandrosterone [DHEA]) were measured before and after therapy. Data were analyzed by Chi-square and McNemar's tests. Results: Significant decreases were seen after treatment with metformin in extent of hair loss (P = 0.008), wrist circle (P = 0.011), weight (P = 0.047), diastolic BP (P = 0.023), and DHEA (P = 0.035). A significant decrease in TG was seen with pioglitazone treatment (P = 0.047). In both groups, significant decreases in acne, menstrual disturbance, FBS, and serum insulin were seen. Conclusion: There is a significant amelioration of endocrine and metabolic indices with pioglitazone in PCOS patients. Although we were not able to recommend one treatment regime over the other, pioglitazone offers a useful, alternate treatment in women with PCOS who are not able to tolerate metformin. PMID:27867884

  3. Toll-like Receptor 4 Signaling Pathway in the Protective Effect of Pioglitazone on Experimental Immunoglobulin A Nephropathy

    Directory of Open Access Journals (Sweden)

    Jia-Nan Zou

    2017-01-01

    Conclusions: Our study proves that inflammation mediated by TLR4 signaling pathway is involved in the progression of IgAN in rat models. Moreover, pioglitazone can inhibit the expression of TLR4 in IgAN.

  4. Middle cerebral artery stenosis associated with moyamoya pattern collateralization

    Directory of Open Access Journals (Sweden)

    Randall Edgell

    2010-11-01

    Full Text Available Background and Purpose: Moyamoya disease is a well described phenomenon presenting with terminal internal carotid artery occlusion and rete pattern of collateralization around the occlusion. The development of moyamoya-like collaterals secondary to isolated middle cerebral artery stenosis or occlusion and the natural history of this entity in Caucasians have not been well described. Methods: Cerebral angiograms and CT angiograms performed between August 2004 and August of 2006 demonstrating moyamoya collateralization at a single US center were retrospectively reviewed. All cases of middle cerebral artery stenosis associated with a rete pattern of collateralization were included in this series. Demographic, clinical, and angiographic data were obtained. Results: There were 3 cases of middle cerebral artery stenosis associated with a moyamoya pattern of collateralization. The average age of the patients was 36 years old, 2 were male, and all were Caucasian. All patients presented with ischemic symptoms. The average degree of stenosis was 91%. No stenosis was seen in the supraclinoid internal carotid arteries or elsewhere in the intracranial vasculature. Conclusion: We describe a moyamoya-like pattern of anastomosis associated with isolated severe middle cerebral artery stenosis or occlusion in Caucasians.

  5. Free carnitine and acylcarnitines in obese patients with polycystic ovary syndrome and effects of pioglitazone treatment

    DEFF Research Database (Denmark)

    Vigerust, Natalya Filipchuk; Bohov, Pavol; Bjørndal, Bodil;

    2012-01-01

    To determine fasting and insulin-stimulated levels of carnitine precursors, total and free carnitine, and acylcarnitines, and evaluate the impact of pioglitazone treatment in obese patients with polycystic ovary syndrome (PCOS).......To determine fasting and insulin-stimulated levels of carnitine precursors, total and free carnitine, and acylcarnitines, and evaluate the impact of pioglitazone treatment in obese patients with polycystic ovary syndrome (PCOS)....

  6. Pioglitazone is an effective treatment for patients with post-stroke depression combined with type 2 diabetes mellitus.

    Science.gov (United States)

    Hu, Yaozhi; Xing, Haiyan; Dong, Xiaomeng; Lu, Wenxian; Xiao, Xinxing; Gao, Lilin; Cui, Minghu; Chen, Jinbo

    2015-09-01

    The antidepressive effects of the antidiabetic medicine, pioglitazone, were recently reported in several studies. These effects may ameliorate the depressive symptoms of patients with post-stroke depression (PSD). The present study aimed to evaluate the antidepressive effect of pioglitazone in patients with PSD combined with type 2 diabetes. A total of 118 consecutive patients with stroke who had depression were studied for an average of 3 months. The Diagnostic and Statistical Manual of Mental Disorders (fourth edition) was used to assess whether a patient was depressed or not. The severity of depression was evaluated by the Hamilton depression rating scale (HAMD). In accordance with their HAMD scores, the 118 patients were divided into a severe depression group (n=40) and a mild and moderate (MM) depression group (n=78). These subjects were then divided into pioglitazone [30 mg once daily (qd)] and metformin (0.5 g twice daily) subgroups. All patients were given fluoxetine (20 mg qd). Follow-up evaluations, which included HAMD scores, activities of daily living (ADL) scores, fasting blood glucose (FBG) levels and fasting insulin (FINS) levels, were conducted on the first and third month following the beginning of the treatment. In the MM depression group, the HAMD score in the pioglitazone subgroup was lower than that in the metformin subgroup following treatment for 1 or 3 months. In the severe depression group, the HAMD score in the pioglitazone subgroup was lower than that in the metformin subgroup following 3 months of treatment. The FINS levels of the pioglitazone subgroup gradually decreased in the 3 months of treatment. No noticeable improvement was observed in the ADL scores and FBG values. In conclusion, the results of the current study demonstrate that pioglitazone effectively decreased HAMD scores and FINS values in patients with PSD, suggesting that pioglitazone may be useful for the treatment of patients with PSD combined with type 2 diabetes.

  7. Efficacy and tolerability of pioglitazone in patients with type 2 diabetes mellitus: comparison with other oral antihyperglycaemic agents.

    Science.gov (United States)

    Derosa, Giuseppe

    2010-10-22

    Diabetes mellitus is a debilitating disease that is estimated to affect 366 million people by the year 2030. Type 2 diabetes mellitus (T2DM) is characterized by a progressive decline in pancreatic β-cell function and increased insulin resistance, and accounts for approximately 90% of people with diabetes. Oral antihyperglycaemic agents are extensively used in the treatment of T2DM. Thiazolidinediones are insulin sensitizers developed specifically for T2DM, which act via activation of peroxisome proliferator-activated receptors (PPARs). Pioglitazone is a thiazolidinedione that displays high affinity for PPARγ(1) and PPARγ(2), which are predominately expressed in adipose tissue. This review examines the published literature comparing the efficacy and tolerability of pioglitazone with other oral antihyperglycaemic agents in the treatment of patients with T2DM. Glycosylated haemoglobin, fasting glucose, insulin parameters and β-cell function are all improved with pioglitazone treatment, with efficacy similar to third-generation sulfonylureas, metformin and dipeptidyl peptidase-4 inhibitors. Pioglitazone reduces vascular risk and inflammatory markers, and improves carotid intima media thickness independent of its glycaemic effect. When compared with rosiglitazone, pioglitazone is associated with a reduction in the risk of hospitalization for acute myocardial infarction. Blood pressure is reduced and lipid profiles are favourably improved with pioglitazone; however, an increased risk for the development/exacerbation of heart failure, which is related to the increased incidence of oedema due to fluid retention, and fractures remain a concern. A low incidence of hypoglycaemia is observed with pioglitazone, especially compared with sulfonylureas. In conclusion, pioglitazone is an effective oral antihyperglycaemic agent with additional cardiovascular and lipid benefits that allows for the successful management of patients with T2DM.

  8. Collateral vessels in moyamoya disease : comparison of MR and MRA with conventional angiography

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Joo Eun; Yoon, Dae Young; Yi, Jeong Geun; Kim, Ho Chul; Choi, Chul Sun; Bae, Sang Hoon [Hallym University College of Medicine, Choonchun (Korea, Republic of)

    1998-01-01

    To determine the value of magnetic resonance imaging (MR) and magnetic resonance angiography (MRA) in assessing collateral vessels of moyamoya disease. Twenty-four patients with moyamoya disease who underwent MR, 3D TOF MRA, and conventional angiography participated in this study. Two radiologists working independently and with no knowledge of the angiographic findings, interpreted the MR and MRA images. To determine the presence of parenchymal and leptomeningeal collaterals (48 hemispheres) and transdural collaterals (38 hemispheres in 19 patients were depicted by angiography of the external carotid), the findings were compared with those of angiography. Parenchymal, leptomeningeal, and transdural collaterals were depicted by conventional angiography in 34 (71%), 32 (67%), and 11 (29%) hemispheres respectively. The sensitivity and specificity of MR/MRA for collateral vessels were 79.1/88.1 % for parenchymal collaterals, 72.1/88.1 % for leptomeningeal collaterals, and 0.1/18.1 % for transdural collaterals, respectively. Respective sensitivity and specificity of MR/MRA were 88.94/94.1% for leptomeningeal collaterals, and 18.93/55.1 % for transdural collaterals, when the prominent posterior cerebral and external carotid artery were regarded as secondary signs of leptomeningeal and transdural collateral vessels. In moyamoya disease, MR and MRA are useful imaging modalities for the assessment of collateral vessels. The prominent posterior cerebral artery and external carotid artery can be useful secondary signs of leptomeningeal and transdural collateral vessels. (author). 18 refs., 2 figs.

  9. Pioglitazone protects against cisplatin induced nephrotoxicity in rats and potentiates its anticancer activity against human renal adenocarcinoma cell lines.

    Science.gov (United States)

    Mahmoud, Mona F; El Shazly, Shimaa M

    2013-01-01

    Cisplatin-induced nephrotoxicity is a serious problem that limits its use in cancer treatment. The present study aimed to investigate the renal protective capacity of pioglitazone to reduce the cisplatin- induced nephrotoxicity. The underlying suggested mechanism(s) and whether this nephroprotective effect (if any) interferes with the cytotoxic effect of cisplatin on cancer cells were also investigated. Pioglitazone, Bisphenol A diglycidyl ether, BADGE, IP injected (Peroxisome proliferator- activated receptor gamma (PPAR-γ) antagonist), or their combination were administered to rats one hour before cisplatin injection. Moreover, their effects on the cell viability of human renal adenocarcinoma cell models (ACHN) were studied. The obtained results showed that pioglitazone improved the renal function, structural changes, renal malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (NF-κB) genes expression in cisplatin injected rats. It increased both renal reduced glutathione (GSH) content and PPAR-γ gene expression. In contrast to the data obtained by prior administration of BADGE. Pioglitazone also potentiated the cytotoxic effect of cisplatin on human renal adenocarcinoma cells and this effect was abolished by BADGE co administration. In conclusion, these results suggested that pioglitazone protected against cisplatin- induced nephrotoxicity through its interaction with PPAR-γ receptors and antioxidant effects. Furthermore, pioglitazone did not interfere but rather potentiated the cytotoxic effects of cisplatin on human renal adenocarcinoma cells.

  10. Coefficient of beta-cell failure in patients with type 2 diabetes treated with pioglitazone or acarbose.

    Science.gov (United States)

    Göke, B; Lübben, G; Bates, P C

    2004-02-01

    A new method of assessing the coefficient of failure of pancreatic beta-cells from any index of glycaemia has been proposed. This method of analysis has been used to assess data on HbA1c and fasting glucose concentrations from a randomised study comparing pioglitazone with acarbose. Patients were treated for 26 weeks with either pioglitazone 45 mg once daily or acarbose 300 mg/day as 3 equal doses. Plasma HbA1c concentration was measured every two months and fasting glucose was measured monthly. The coefficient of failure was determined for each patient from the slope of the least squares regression line over time. The coefficient of failure from HbA1c was - 2.65 +/- 2.13 %/year with pioglitazone and - 1.25 +/- 3.11 %/year with acarbose, indicating improved beta-cell function in each case. The coefficient of failure was improved to a significantly greater extent with pioglitazone ( P Coefficient of failure from fasting blood glucose also showed a greater improvement with pioglitazone (- 53.1 +/- 95.0 mg/dl/year) than with acarbose (- 29.9 +/- 142.5 mg/dl/year; p = 0.049). The coefficient of failure showed a significantly greater improvement of beta-cell function with pioglitazone than with acarbose during 26 weeks of treatment.

  11. Effect of Chronic Pioglitazone Treatment on Hepatic Gene Expression Profile in Obese C57BL/6J Mice.

    Science.gov (United States)

    Jia, Chunming; Huan, Yi; Liu, Shuainan; Hou, Shaocong; Sun, Sujuan; Li, Caina; Liu, Quan; Jiang, Qian; Wang, Yue; Shen, Zhufang

    2015-05-29

    Pioglitazone, a selective ligand of peroxisome proliferator-activated receptor gamma (PPARγ), is an insulin sensitizer drug that is being used in a number of insulin-resistant conditions, including non-alcoholic fatty liver disease (NAFLD). However, there is a discrepancy between preclinical and clinical data in the literature and the benefits of pioglitazone treatment as well as the precise mechanism of action remain unclear. In the present study, we determined the effect of chronic pioglitazone treatment on hepatic gene expression profile in diet-induced obesity (DIO) C57BL/6J mice in order to understand the mechanisms of NAFLD induced by PPARγ agonists. DIO mice were treated with pioglitazone (25 mg/kg/day) for 38 days, the gene expression profile in liver was evaluated using Affymetrix Mouse GeneChip 1.0 ST array. Pioglitazone treatment resulted in exacerbated hepatic steatosis and increased hepatic triglyceride and free fatty acids concentrations, though significantly increased the glucose infusion rate in hyperinsulinemic-euglycemic clamp test. The differentially expressed genes in liver of pioglitazone treated vs. untreated mice include 260 upregulated and 86 downregulated genes. Gene Ontology based enrichment analysis suggests that inflammation response is transcriptionally downregulated, while lipid metabolism is transcriptionally upregulated. This may underlie the observed aggravating liver steatosis and ameliorated systemic insulin resistance in DIO mice.

  12. The influence of nicotine on pioglitazone encapsulation into carbon nanotube: the investigation of molecular dynamic and density functional theory.

    Science.gov (United States)

    Zaboli, Maryam; Raissi, Heidar

    2017-02-01

    In this work, molecular dynamics simulations of the insertion of pioglitazone into the nanotube with chirality (10, 10) at 400 K and 1 bar in the presence and absence of nicotine molecules and in different drug concentrations have been studied. The main aim is consideration of the effect of nicotine in the drug encapsulation process. The results indicate that encapsulation of pioglitazone could be attributed to the water flow via van der Waals and hydrophilic interactions. Because of the existence of the partial π-π interactions between aromatic rings of pioglitazone and the conjugated aromatic rings of nanotube, pioglitazone molecule can enter inside the nanotube. Some physical properties such as hydrogen bonding, number of contacts, also, the diffusion coefficient of the pioglitazone and water molecules, and variation of the center of mass have been calculated during the simulation. Furthermore, computing the electronic structure has also been done on model systems for quantitative determination of the adsorption energy (Eads). The B3LYP/6-31G* level calculations on four different configurations of pioglitazone/carbon nanotube (CNT) and nicotine/CNT show that the interaction of drug with the inside of the nanotube is stronger than the other forms.

  13. Collateral branching of long-distance cortical projections in monkey.

    Science.gov (United States)

    Rockland, Kathleen S

    2013-12-15

    Collateralization of individual cortical axons is well documented for rodents but less so for monkeys, where double retrograde tracer experiments have tended to find only small numbers of neurons projecting to two different injection sites. Evidence from both double label and single axon studies, however, suggests that in specific projection systems the number of neurons with collateralized axons can be 10% or greater. These include feedback projections from temporal areas (but less so those from V4 and MT/V5). Single-axon analyses show that many parietal neurons branch to multiple targets. Except for giant Meynert cells in area V1, feedforward projections from early visual areas have only a small number of neurons with branching axons. Why only some neurons collateralize, what determines branch points and projection foci, and how this impacts network organization are largely unknown. Deciphering the branching code might offer new perspectives on space-time organization at the network level.

  14. Documenting and Automating Collateral Evolutions in Linux Device Drivers

    DEFF Research Database (Denmark)

    Padioleau, Yoann; Lawall, Julia Laetitia; Hansen, Rene Rydhof

    2008-01-01

    The internal libraries of Linux are evolving rapidly, to address new requirements and improve performance. These evolutions, however, entail a massive problem of collateral evolution in Linux device drivers: for every change that affects an API, all dependent drivers must be updated accordingly....... Because Linux programmers are accustomed to manipulating program modifications in terms of patch files, this tool uses a language based on the patch syntax to express transformations, extending patches to semantic patches. Coccinelle preserves the coding style of the original driver, as would a human...... programmer. We have evaluated our approach on 62 representative collateral evolutions that were previously performed manually in Linux 2.5 and 2.6. On a test suite of over 5800 relevant driver files, the semantic patches for these collateral evolutions update over 93% of the files completely...

  15. Documenting and Automating Collateral Evolutions in Linux Device Drivers

    DEFF Research Database (Denmark)

    Padioleau, Yoann; Lawall, Julia Laetitia; Hansen, Rene Rydhof

    2008-01-01

    The internal libraries of Linux are evolving rapidly, to address new requirements and improve performance. These evolutions, however, entail a massive problem of collateral evolution in Linux device drivers: for every change that affects an API, all dependent drivers must be updated accordingly....... Because Linux programmers are accustomed to manipulating program modifications in terms of patch files, this tool uses a language based on the patch syntax to express transformations, extending patches to semantic patches. Coccinelle preserves the coding style of the original driver, as would a human...... programmer. We have evaluated our approach on 62 representative collateral evolutions that were previously performed manually in Linux 2.5 and 2.6. On a test suite of over 5800 relevant driver files, the semantic patches for these collateral evolutions update over 93% of the files completely...

  16. Vascular collateralization along ventriculoperitoneal shunt catheters in moyamoya disease.

    Science.gov (United States)

    Singla, Amit; Lin, Ning; Ho, Allen L; Scott, R Michael; Smith, Edward R

    2013-06-01

    Surgically created openings such as bur holes can serve as avenues for the development of collateral blood supply to the brain in patients with moyamoya disease. When such collateralization occurs through preexisting shunt catheter sites, the potential exists for perioperative stroke if these vessels are damaged during revision of a ventricular catheter for shunt malfunction. In this paper the authors report on a series of patients with a history of ventriculoperitoneal (VP) shunts who later developed moyamoya disease and were found to have spontaneous transdural collateral vessels at ventricular catheter sites readily visualized on diagnostic angiography. A consecutive surgical series of 412 patients with moyamoya disease treated at Boston Children's Hospital from 1990 to 2010 were reviewed to identify patients with concomitant moyamoya and a VP shunt. The clinical records and angiograms of these patients were reviewed to determine the extent of bur hole collaterals through the shunt site. Three patients were identified who had VP shunts placed for hydrocephalus and subsequently developed moyamoya disease. All 3 patients demonstrated spontaneous transdural collaterals at the ventricular catheter bur hole, as confirmed by angiography during the workup for moyamoya disease. No patients required subsequent revision of their ventricular catheters following the diagnosis of moyamoya. All patients have remained stroke free and clinically stable following pial synangiosis. Although the association of moyamoya and shunted hydrocephalus is rare, it may present a significant potential problem for the neurosurgeon treating a shunt malfunction in this patient population, because shunt bur holes may become entry sites for the ingrowth of significant cortical transdural collateral blood supply to the underlying brain. Shunt revision might therefore be associated with an increased risk of postoperative stroke or operative-site hemorrhage in this population if this

  17. Pioglitazone is equally effective for diabetes prevention in older versus younger adults with impaired glucose tolerance.

    Science.gov (United States)

    Espinoza, Sara E; Wang, Chen-Pin; Tripathy, Devjit; Clement, Stephen C; Schwenke, Dawn C; Banerji, Mary Ann; Bray, George A; Buchanan, Thomas A; Henry, Robert R; Kitabchi, Abbas E; Mudaliar, Sunder; Stentz, Frankie B; Reaven, Peter D; DeFronzo, Ralph A; Musi, Nicolas

    2016-12-01

    To determine the efficacy of pioglitazone to prevent type 2 diabetes in older compared to younger adults with pre-diabetes. Six hundred two participants with impaired glucose tolerance (IGT) were randomized in double blind fashion to placebo or pioglitazone for diabetes prevention in the ACT NOW study (NEJM 364:1104-1115, 2011). Cox proportional hazard regression was used to compare time to development of diabetes over a mean of 2 years between older (≥61 years) and younger participants. We compared effects of pioglitazone versus placebo on metabolic profiles, inflammatory markers, adipokines, β cell function (disposition index), insulin sensitivity (Matsuda index), and body composition by ANOVA. Diabetes incidence was reduced by 85 % in older and 69 % in younger subjects (p = 0.41). β cell function (disposition index) increased by 35.0 % in the older and 26.7 % in younger subjects (p = 0.83). Insulin sensitivity (Matsuda index) increased by 3.07 (5.2-fold) in older and by 2.54 (3.8-fold) in younger participants (p = 0.58). Pioglitazone more effectively increased adiponectin in older versus younger subjects (22.9 ± 3.2 μg/mL [2.7-fold] vs. 12.7 ± 1.4 μg/mL [2.2-fold], respectively; p = 0.04). Younger subjects tended to have a greater increase in whole body fat mass compared to older subjects (3.6 vs. 3.1 kg; p = 0.061). Younger and older subjects had similar decreases in bone mineral density (0.018 ± 0.0071 vs. 0.0138 ± 0.021 g/cm(2)). Younger and older pre-diabetic adults taking pioglitazone had similar reductions in conversion to diabetes and older adults had similar or greater improvements in metabolic risk factors, demonstrating that pioglitazone is useful in preventing diabetes in older adults.

  18. Pioglitazone and bladder cancer in human studies: is it diabetes itself, diabetes drugs, flawed analyses or different ethnicities?

    Science.gov (United States)

    Tseng, Chin-Hsiao

    2012-03-01

    This article reviews human observations on pioglitazone and bladder cancer risk. The PROspective pioglitAzone Clinical Trial In macroVascular Events trial showed an imbalance in bladder cancer between users of pioglitazone and placebo (14 versus six cases, p = 0.069). However, after excluding bladder cancer probably ascribed to other etiology, a blind assessment concluded that the imbalance might not be related to pioglitazone. Epidemiologic studies conducted in the United States and France using insurance databases independently suggested that pioglitazone use for >2 years might confer a 20%-40% higher risk. Another study evaluating bladder cancer risk in diabetic patients using the National Health Insurance in Taiwan did not find any incident bladder cancer case among 422 pioglitazone users for a follow-up of up to 3 years. Because observational studies may suffer from selection and information bias, and inadequate adjustment for confounders may inflate the estimated risk, causal inference from these studies should be interpreted with caution. While investigating cancer risk associated with a medication, indication bias should also be attended, especially when the medication is used at a late stage of the disease. Because pioglitazone is usually a second or third line antidiabetic agent, the users are always characterized by older age, longer diabetes duration, poorer glycemic control, and higher rates of complications and comorbidities. Biased estimates will also result if these differences are not appropriately addressed in the analyses. Current evidence neither concludes nor excludes a causal role of pioglitazone on bladder cancer. Clinical trials aiming at evaluating the risk of cancer associated with a medication is not ethical and may not be expected to provide an answer on the issue of pioglitazone-related bladder cancer. However, a meta-analysis using all available clinical trials to compare the bladder cancer risk between pioglitazone and comparators

  19. Vascular endothelial growth factor and hypoxia-inducible factor-1α gene polymorphisms and coronary collateral formation in patients with coronary chronic total occlusions

    Directory of Open Access Journals (Sweden)

    Vincent Amoah

    2016-06-01

    Full Text Available Introduction: We evaluated the association between two single nucleotide polymorphisms of the vascular endothelial growth factor gene and one of the hypoxia-inducible factor-1α gene and the degree of coronary collateral formation in patients with a coronary chronic total occlusion. Methods: Totally, 98 patients with symptomatic coronary artery disease and a chronic total occlusion observed during coronary angiography were recruited. Genotyping of two vascular endothelial growth factor promoter single nucleotide polymorphisms (−152G>A and −165C>T and the C1772T single nucleotide polymorphism of hypoxia-inducible factor-1α were performed using polymerase chain reaction and restriction fragment length polymorphism analysis. The presence and extent of collateral vessel filling was scored by blinded observers using the Rentrop grade. Results: We found no association between the vascular endothelial growth factor −152G>A, −165C>T and hypoxia-inducible factor-1α −1772C>T with the presence and filling of coronary collateral vessels. A history of percutaneous coronary intervention and transient ischaemic attack/cerebrovascular accident were associated with the presence of enhanced collateral vessel formation following binary logistic regression analysis. Conclusion: The study findings suggest that coronary collateral formation is not associated with the tested polymorphic variants of vascular endothelial growth factor and hypoxia-inducible factor-1α in patients with symptomatic coronary artery disease and the presence of a chronic total occlusion.

  20. 7 CFR 1421.106 - Warehouse-stored marketing assistance loan collateral.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Warehouse-stored marketing assistance loan collateral... Marketing Assistance Loans § 1421.106 Warehouse-stored marketing assistance loan collateral. (a) A commodity may be pledged as collateral for a warehouse-stored marketing assistance loan in the...

  1. RP-HPLC METHOD FOR SIMULTANEOUS ESTIMATION OF SEXAGLIPTIN AND PIOGLITAZONE IN TABLETS

    Directory of Open Access Journals (Sweden)

    M.Sarat

    2012-05-01

    Full Text Available A simple, selective, accurate high Performance Liquid Chromatographic (HPLC method was developed and validated for the analysis of Sexagliptin and Pioglitazone. Chromatographic separation achieved isocratically on a C18 column [Use Inertsil C18, 5m , 150 mm x 4.6 mm] utilizing a mobile phase of acetonitrile/phosphate buffer (60:40, v/v, pH 7.0 at a flow rate of 0.8 ml/min with UV detection at 260nm.Aceclofenac was used as an internal standard. The retention time of Sexagliptin, pioglitazone and aceclofenac was 2.48, 4.45 and 6.34 min respectively. The developed method was validated in terms of accuracy, precision, linearity, limit of detection, limit of quantitation.This study aimed at developing and validating an HPLC method, being simple, accurate and selective, and the proposed method can be used for the estimation of these drugs in combined dosage forms.

  2. [Insulin sensitizer--anti-diabetic drugs, metformin and pioglitazone that can improve insulin resistance].

    Science.gov (United States)

    Korenaga, Masaaki; Kawaguchi, Koutaro; Korenaga, Keiko; Uchida, Kouichi; Sakaida, Iso

    2006-06-01

    Nonalcoholic steatohepatitis (NASH), which is considered the hepatic manifestation of the metabolic syndrome is an increasingly cause of chronic liver disease in Japan. NASH is finally lead to liver cirrhosis and hepatocellular carcinoma as viral hepatitis, therefore, medical treatment should be considered, when NASH occurs. Treatment of patients with metabolic syndrome has been focused on the management of associated conditions such as obesity, hyperlipidemia, hypertension and hyperinsulinemia. Insulin resistance, that could accelerate liver inflammation and fibrosis by up-regulation of TNFa seems to be most important factor in many cases of NASH. The insulin-sensitizing drugs, which were biguanides (metformin) and thiazolidinediones (pioglitazone) have been shown to correct not only insulin resistance but also steatosis and inflammation in the liver. Metformin and pioglitazone might be useful drugs against NASH, however further investigations were needed.

  3. Pioglitazone: a valuable component of combination therapy for type 2 diabetes mellitus.

    Science.gov (United States)

    Papanas, Nikolaos; Katsiki, Niki; Hatzitolios, Apostolos I; Maltezos, Efstratios

    2011-07-01

    Several classes of drugs have been developed to treat type 2 diabetes mellitus (T2DM). Pioglitazone is now the only thiazolidinedione approved for the treatment of T2DM and can be administered in combination with metformin, sulfonylureas, exenatide, dipeptidyl peptidase 4 (DPP-4) inhibitors or insulin. It improves glycemic control with an extremely low incidence of hypoglycemia. In addition to reducing insulin resistance, it may also improve pancreatic beta-cell secretory function. Moreover, it exhibits a variety of favorable pleiotropic effects. The latter include anti-inflammatory, antioxidant, vasoprotective, antihypertensive and hypolipidemic actions. Finally, this agent has been shown to improve experimental diabetic neuropathy and alleviate neuropathic pain, as well as decreasing urinary albumin excretion in patients with diabetes. Thus, pioglitazone emerges as a valuable hypoglycemic agent for combination therapy in T2DM. Importantly, however, patients should be appropriately selected, especially to avoid those with heart failure, in order to minimize adverse events attributable to water retention.

  4. Pioglitazone could induce remission in major depression: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Colle R

    2016-12-01

    Full Text Available Romain Colle,1,* Delphine de Larminat,1,* Samuel Rotenberg,1 Franz Hozer,1 Patrick Hardy,1 Céline Verstuyft,2 Bruno Fève,3,* Emmanuelle Corruble1,* 1Psychiatry Department, Hôpital Bicêtre, INSERM, UMR S1178, University Paris-Sud, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France; 2Molecular Genetic, Pharmacogenetics and Hormonology Department, Hôpital Bicêtre, INSERM UMR_S1184, Centre IMVA, University Paris-Sud, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France; 3Endocrinology Department, INSERM UMR_S938, Hôpital Saint-Antoine, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire ICAN, Sorbonne Universités, Université Pierre et Marie Curie, Assistance Publique des Hôpitaux de Paris, Paris, France *These authors contributed equally to this work Background: Pioglitazone, a selective agonist of the nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-γ, prescribed for the treatment of type 2 diabetes, could have antidepressant properties. However, its potential to induce remission of major depressive episodes, the optimal clinical target for an antidepressant drug, is a matter of concern. Indeed, only one out of four double-blind randomized controlled trials show higher remission rates with pioglitazone than with control treatments. Hence, the main aim of this study was to perform a meta-analysis of the efficacy of pioglitazone for the treatment of MDE, focusing on remission rates.Methods: Four double-blind randomized controlled trials, comprising 161 patients with an MDE, were included in this meta-analysis. Pioglitazone was studied either alone (one study or as add-on therapy to conventional treatments (antidepressant drugs or lithium salts. It was compared either to placebo (three studies or to metformin (one study. Remission was defined by a Hamilton Depression Rating Scale score <8 after treatment.Results: Pioglitazone could induce higher remission

  5. 12 CFR 950.9 - Pledged collateral; verification.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Pledged collateral; verification. 950.9 Section 950.9 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOME LOAN BANK ASSETS AND OFF-BALANCE... benefit and subject to the Bank's control and direction. (2) A Bank shall take any steps necessary...

  6. Stiffness of the healing medial collateral ligament of the mouse.

    NARCIS (Netherlands)

    Gijssen, Y.; Sierevelt, I.N.; Kooloos, J.G.M.; Blankevoort, L.

    2004-01-01

    The knee joints of mice can serve as a model for studying knee ligament properties. The goal of our study was to measure the structural stiffness of the medial collateral ligament (MCL) of the murine knee. A tensile test was developed for this purpose. First 84 femur-MCL-tibia complexes of

  7. Endobronchial Valves for Emphysema without Interlobar Collateral Ventilation

    NARCIS (Netherlands)

    Klooster, Karin; ten Hacken, Nick H T; Hartman, Jorine E.; Kerstjens, Huib A. M.; van Rikxoort, Eva M.; Slebos, Dirk-Jan

    2015-01-01

    BACKGROUND Bronchoscopic lung-volume reduction with the use of one-way endobronchial valves is a potential treatment for patients with severe emphysema. To date, the benefits have been modest but have been hypothesized to be much larger in patients without interlobar collateral ventilation than in

  8. Imaging findings of unusual intra- and extrahepatic portosystemic collaterals

    Energy Technology Data Exchange (ETDEWEB)

    Ito, K. [Department of Radiology, Yamaguchi University School of Medicine, Yamaguchi (Japan)], E-mail: itokatsu@med.kawasaki-m.ac.jp; Fujita, T.; Shimizu, A.; Sasaki, K.; Tanabe, M.; Matsunaga, N. [Department of Radiology, Yamaguchi University School of Medicine, Yamaguchi (Japan)

    2009-02-15

    We describe unusual portosystemic shunts demonstrated using computed tomography (CT) and magnetic resonance imaging (MRI), including gallbladder varices, aberrant left gastric vein to left portal vein collaterals, intrahepatic and transhepatic portosystemic venous shunt, and mesenteric varices. Familiarity with the CT and MRI features of unusual portosystemic shunts will help in making the correct diagnosis for affected patients.

  9. Pioglitazone, quercetin and hydroxy citric acid effect on hepatic biomarkers in Non Alcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Krishna Mohan Surapaneni

    2014-01-01

    Full Text Available Background: Non alcoholic steatohepatitis (NASH, severe form of diseases belonging to the spectrum of the Non alcoholic fatty liver disease (NAFLD. It is an asymptomatic disease which leads to fibrosis and finally to cirrhosis, an end stage liver disease. Objective: To study the effect of pioglitazone, quercetin and hydroxy citric acid on hepatic biomarkers and various biochemical parameters in experimentally induced non alcoholic steatohepatitis (NASH. Materials and Methods: Male Wister rats were divided into 8 groups. The activities of alkaline phosphatase (ALP, aspartate transaminase (AST, alanine transaminase (ALT, lactate dehydrogenase (LDH and γ-Glutamyl Transferase (GGT were assayed in serum. The levels of various other biochemical parameters such as serum albumin, total bilirubin, creatinine, urea, uric acid and glucose were also estimated in experimental NASH. Results: The NASH group produced severe liver injury by significantly increasing the serum levels of ALT, AST, GGT and LDH compared with that of the control. However, the experimental NASH rats treated with pioglitazone, with quercetin and with hydroxy citric acid showed an obvious decrease in ALT, AST, GGT and LDH levels when compared with that of NASH induced group. A significant increase in the levels of albumin, creatinine, urea, uric acid, glucose and total bilirubin was noticed in experimentally induced NASH group (group 2 when compared to rats in control group (group 1. Conclusion: It could be inferred from this study that, pioglitazone, quercetin and hydroxy citric acid may afford protection to the liver against NASH, as evidenced by the results of this study on the levels of various biochemical parameters such as glucose, urea, uric acid, creatinine and bilirubin. Whereas from the results of hepatic marker enzymes, it is evident that optimal protection was observed after quercetin treatment against experimental NASH whereas pioglitazone and hydroxy citric acid also

  10. Formulation and Evaluation of Multilayered Tablets of Pioglitazone Hydrochloride and Metformin Hydrochloride

    Directory of Open Access Journals (Sweden)

    Y. Ankamma Chowdary

    2014-01-01

    Full Text Available In the treatment of type 2 diabetes mellitus a continuous therapy is required which is a more complex one. As in these patients there may be a defect in both insulin secretion and insulin action exists. Hence, the treatment depends on the pathophysiology and the disease state. In the present study, multilayered tablets of pioglitazone hydrochloride 15 mg and metformin hydrochloride 500 mg were prepared in an attempt for combination therapy for the treatment of type 2 diabetes mellitus. Pioglitazone HCl was formulated as immediate release layer to show immediate action by direct compression method using combination of superdisintegrants, namely, crospovidone and avicel PH 102. Crospovidone at 20% concentration showed good drug release profile at 2 hrs. Metformin HCl was formulated as controlled release layer to prolong the drug action by incorporating hydrophilic polymers such as HPMC K4M by direct compression method and guar gum by wet granulation method in order to sustain the drug release from the tablets and maintain its integrity so as to provide a suitable formulation. The multilayered tablets were prepared after carrying out the optimization of immediate release layer and were evaluated for various precompression and postcompression parameters. Formulation F13 showed 99.97% of pioglitazone release at 2 hrs in 0.1 N HCl and metformin showed 98.81% drug release at 10 hrs of dissolution in 6.8 pH phosphate buffer. The developed formulation is equivalent to innovator product in view of in vitro drug release profile. The results of all these evaluation tests are within the standards. The procedure followed for the formulation of these tablets was found to be reproducible and all the formulations were stable after accelerated stability studies. Hence, multilayered tablets of pioglitazone HCl and metformin HCl can be a better alternative way to conventional dosage forms.

  11. Protective effect of pioglitazone, a PPARγ agonist against acetaminophen-induced hepatotoxicity in rats.

    Science.gov (United States)

    Gupta, Gaurav; Krishna, Gopala; Chellappan, Dinesh Kumar; Gubbiyappa, Kumar Shiva; Candasamy, Mayuren; Dua, Kamal

    2014-08-01

    Acetaminophen has a reasonable safety profile when consumed in therapeutic doses. However, it could induce hepatotoxicity and even acute liver failure when taken at an overdose. Pioglitazone, PPARγ ligand, is clinically tested and used in treatment of diabetes. PPARγ is a key nuclear hormone receptor of lipid metabolisms and regulates several gene transcriptions associated with differentiation, growth arrest, and apoptosis. The aim of our study was to evaluate the hepatoprotective activity of pioglitazone on acetaminophen-induced hepatotoxicity and to understand the relationship between the PPARγ and acetaminophen-induced hepato injury. For the experiment, Sprague-Dawley rats (160-180 g) were used and divided into four groups. Groups I and II were normal and experimental controls, respectively. Groups III and IV received the pioglitazone 20 mg/kg for 10 days. Hepatotoxicity was induced in Groups II and III on the eighth day with acetaminophen (i.p. 350 mg/kg body weight). The hepatoprotective effect was evaluated by performing an assay of the total protein, total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and α-fetoprotein as well as glutathione peroxidase, lipid peroxidation, catalase, superoxide dismutase, and glutathione transferase and liver histopathology. The assay results were presented as mean and standard error of mean for each group. The study group was compared with the control group by one-way ANOVA test. A p value of hepatotoxicity. Liver histopathological examination showed that pioglitazone administration antagonized acetaminophen -induced liver pathological damage. Various biochemical estimations of different hepatic markers and antioxidant enzymes and histopathological studies of liver tissues glimpse a support to its significant hepatoprotective activity on acetaminophen -induced hepatotoxicity.

  12. Pioglitazone administration alters ovarian gene expression in aging obese lethal yellow mice

    Directory of Open Access Journals (Sweden)

    Weber Mitch

    2008-03-01

    Full Text Available Abstract Background Women with polycystic ovary syndrome (PCOS are often treated with insulin-sensitizing agents, e.g. thiazolidinediones (TZD, which have been shown to reduce androgen levels and improved ovulatory function. Acting via peroxisome proliferator-activated receptor (PPAR gamma, TZD alter the expression of a large variety of genes. Lethal yellow (LY; C57BL/6J Ay/a mice, possessing a mutation (Ay in the agouti gene locus, exhibit progressive obesity, reproductive dysfunction, and altered metabolic regulation similar to women with PCOS. The current study was designed to test the hypothesis that prolonged treatment of aging LY mice with the TZD, pioglitazone, alters the ovarian expression of genes that may impact reproduction. Methods Female LY mice received daily oral doses of either 0.01 mg pioglitazone (n = 4 or an equal volume of vehicle (DMSO; n = 4 for 8 weeks. At the end of treatment, ovaries were removed and DNA microarrays were used to analyze differential gene expression. Results Twenty-seven genes showed at least a two-fold difference in ovarian expression with pioglitazone treatment. These included leptin, angiopoietin, angiopoietin-like 4, Foxa3, PGE1 receptor, resistin-like molecule-alpha (RELM, and actin-related protein 6 homolog (ARP6. For most altered genes, pioglitazone changed levels of expression to those seen in untreated C57BL/6J(a/a non-mutant lean mice. Conclusion TZD administration may influence ovarian function via numerous diverse mechanisms that may or may not be directly related to insulin/IGF signaling.

  13. Effects of pioglitazone on expressions of matrix metalloproteinases 2 and 9 in kidneys of diabetic rats

    Institute of Scientific and Technical Information of China (English)

    董凤芹; 李红; 蔡卫民; 陶君; 李群; 阮昱; 郑芬萍; 张哲

    2004-01-01

    Background The changes in matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expressions were examined in the kidneys of diabetic rats to investigate the degradative pathway of collagen type Ⅳ (C-Ⅳ) and the protective effects of pioglitazone on an experimental model of diabetic nephropathy.Methods In 54 SD rats used in our study, 18 served as normal controls. Diabetes mellitus was induced in 36 age- and weight-matched rats by intraperitoneal injection of streptozotocin (70 mg/kg); 18 of the diabetic rats were allocated at random to receive pioglitazone (20 mg*kg-1*d-1) in their drinking water and 18 served as diabetic controls. Rats were killed after 2, 4, or 8 weeks of treatment. Kidneys were examined pathomorphologically and the expressions of MMP-2, MMP-9, and C-Ⅳ were analyzed by immunohistochemistry, and the results were quantified by image analysis techniques.Results Diabetes mellitus was associated with a decrease in the expression of MMP-2 in the glomeruli (P0.05, vs control). The expression of MMP-9 did not show any change when comparing the three groups (P>0.05, vs control). STZ-diabetic rats were also associated with an increase in the expression of C-Ⅳ in the glomeruli and the interstitium (P<0.05, vs control). All diabetes-associated changes in MMP-2 expression were attenuated by pioglitazone treatment in association with reduced C-Ⅳ accumulation. Conclusions These results indicate that a decrease in MMP-2 expression in the glomeruli of diabetic rats may lead to impairment of C-Ⅳ degradation and contribute to the matrix accumulation in diabetic nephropathy. Pioglitazone treatment, which can attenuate the decrease of glomerular MMP-2 and the increase of C-Ⅳ degradation, has curative effects on diabetic nephropathy.

  14. DEVELOPMENT AND EVALUATION OF MICROBALLOONS OF PIOGLITAZONE HYDROCHLORIDE USING EUDRAGIT S-100

    OpenAIRE

    Nishant S. Gandhi et al.

    2012-01-01

    ABSTRACTKeywords:Pioglitazone hydrochloride,Eudragit S-100,Solvent diffusion evaporation,Floating microspheres,Polymer: Drug ratioCorrespondence to Author:Nishant GandhiOld Power House Road, Ramnagar, Gondia, Maharashtra, IndiaVarious approaches have been used to retain the dosage form in the stomach as a way of increasing the gastric residence time (GRT), including floatation systems; high-density systems; mucoadhesive systems; magnetic systems; unfoldable, extendible, or swellable systems;...

  15. PROactive 07: pioglitazone in the treatment of type 2 diabetes: results of the PROactive study

    Directory of Open Access Journals (Sweden)

    Erl

    2007-09-01

    Full Text Available Erland Erdmann1, John Dormandy2, Robert Wilcox3, Massimo Massi-Benedetti4, Bernard Charbonnel51University of Cologne, Cologne, Germany; 2Department of Clinical Vascular Research, St Georges Hospital, London, UK; 3Department of Cardiovascular Medicine, Queen’s Medical Centre, University Hospital, Nottingham, UK; 4University of Perugia, Medicine and Metabolic Diseases, Perugia, Italy; 5Clinique d’Endocrinologie, Hôtel Dieu, Nantes Cedex 1, FranceAbstract: Patients with type 2 diabetes face an increased risk of macrovascular disease compared to those without. Significant reductions in the risk of major cardiovascular events can be achieved with appropriate drug therapy, although patients with type 2 diabetes remain at increased risk compared with non-diabetics. The thiazolidinedione, pioglitazone, is known to offer multiple, potentially antiatherogenic, effects that may have a beneficial impact on macrovascular outcomes, including long-term improvements in insulin resistance (associated with an increased rate of atherosclerosis and improvement in the atherogenic lipid triad (low HDL-cholesterol, raised triglycerides, and a preponderance of small, dense LDL particles that is observed in patients with type 2 diabetes. The recent PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive study showed that pioglitazone can reduce the risk of secondary macrovascular events in a high-risk patient population with type 2 diabetes and established macrovascular disease. Here, we summarize the key results from the PROactive study and place them in context with other recent outcome trials in type 2 diabetes.Keywords: pioglitazone, macrovascular disease, type 2 diabetes, secondary prevention

  16. Pioglitazone alleviates cardiac and vascular remodelling and improves survival in monocrotaline induced pulmonary arterial hypertension.

    Science.gov (United States)

    Behringer, Arnica; Trappiel, Manuela; Berghausen, Eva Maria; Ten Freyhaus, Henrik; Wellnhofer, Ernst; Odenthal, Margarete; Blaschke, Florian; Er, Fikret; Gassanov, Natig; Rosenkranz, Stephan; Baldus, Stephan; Kappert, Kai; Caglayan, Evren

    2016-04-01

    Pulmonary arterial hypertension (PAH) is a fatal disease with limited therapeutic options. Pathophysiological changes comprise obliterative vascular remodelling of small pulmonary arteries, elevated mean pulmonary arterial systolic pressure (PASP) due to elevated resistance of pulmonary vasculature, adverse right ventricular remodelling, and heart failure. Recent findings also indicate a role of increased inflammation and insulin resistance underlying the development of PAH. We hypothesized that treatment of this condition with the peroxisome proliferator-activated receptor-γ (PPARγ) activator pioglitazone, known to regulate the expression of different genes addressing insulin resistance, inflammatory changes, and vascular remodelling, could be a beneficial approach. PAH was induced in adult rats by a single subcutaneous injection of monocrotaline (MCT). Pioglitazone was administered for 2 weeks starting 3 weeks after MCT-injection. At day 35, hemodynamics, organ weights, and -indices were measured. We performed morphological and molecular characterization of the pulmonary vasculature, including analysis of the degree of muscularization, proliferation rates, and medial wall thickness of the small pulmonary arteries. Furthermore, markers of cardiac injury, collagen content, and cardiomyocyte size were analyzed. Survival rates were monitored throughout the experimental period. Pioglitazone treatment improved survival, reduced PASP, muscularization of small pulmonary arteries, and medial wall thickness. Further, MCT-induced right ventricular hypertrophy and fibrosis were attenuated. This was accompanied with reduced cardiac expression of brain natriuretic peptide, as well as decreased cardiomyocyte size. Finally, pulmonary macrophage content and osteopontin gene expression were attenuated. Based on the beneficial impact of pioglitazone, activation of PPARγ might be a promising treatment option in PAH.

  17. Additive Renoprotection by Pioglitazone and Fenofibrate against Inflammatory, Oxidative and Apoptotic Manifestations of Cisplatin Nephrotoxicity: Modulation by PPARs.

    Science.gov (United States)

    Helmy, Mai M; Helmy, Maged W; El-Mas, Mahmoud M

    2015-01-01

    Nephrotoxicity is a major side effect for the antineoplastic drug cisplatin. Here, we employed pharmacological, biochemical, and molecular studies to investigate the role of peroxisome proliferator-activated receptors (PPARs) in cisplatin nephrotoxicity. Rats were treated with a single i.p. dose of cisplatin (5 mg/kg) alone or combined with pioglitazone (PPARγ agonist), fenofibrate (PPARα agonist), pioglitazone plus fenofibrate, or thalidomide (Tumor necrosis factor-α inhibitor; TNF-α). Cisplatin nephrotoxicity was evidenced by rises in renal indices of functional (blood urea nitrogen, BUN, and creatinine), inflammatory (TNF-α, interleukin 6, IL-6), oxidative (increased malondialdehyde, MDA, and decreased superoxide dismutase, SOD and nitric oxide metabolites, NOx), apoptotic (caspase 3), and histological (glomerular atrophy, acute tubular necrosis and vacuolation) profiles. Cisplatin effects were partly abolished upon concurrent exposure to pioglitazone, fenofibrate, or thalidomide; more renoprotection was observed in rats treated with pioglitazaone plus fenofibrate. Immunostaining showed that renal expressions of PPARα and PPARγ were reduced by cisplatin and restored to vehicle-treated values after simultaneous treatment with pioglitazone or fenofibrate. Fenofibrate or pioglitazone renoprotection remained unaltered after concurrent blockade of PPARα (GW6471) and PPARγ (GW9662), respectively. To complement the rat studies, we also report that in human embryonic kidney cells (HEK293 cells), increases caused by cisplatin in inflammatory, apoptotic, and oxidative biomarkers were (i) partly improved after exposure to pioglitazone, fenofibrate, or thalidomide, and (ii) completely disappeared in cells treated with a combination of all three drugs. These data establish that the combined use of pioglitazone and fenofibrate additively improved manifestations of cisplatin nephrotoxicity through perhaps GW6471/GW9662-insensitive mechanisms.

  18. FORMULATION AND EVALUATION OF MUCOADHESIVE MICROSPHERES OF PIOGLITAZONE HYDROCHLORIDE USING A NATURAL POLYMER

    Directory of Open Access Journals (Sweden)

    Mobeen Mohd.

    2015-04-01

    Full Text Available The objective of the present investigation was to design a controlled release dosage form for a thiazolidinedione oral hypoglycemic drug i.e., pioglitazone hydrochloride employing a natural polymer. The present study was also aimed to increase the biological half-life by developing it in the form of sustained release microspheres. The present study aimed at employing a natural polymer in formulating the mucoadhesive microspheres and estimate its effect over the controlled release of the drug from the formulation. The microspheres of pioglitazone hydrochloride were prepared by employing sodium alginate as a cell forming polymer and by using a natural bio-adhesive polymer viz. goru gum in the ratios of 1:1, 1:1.5 and 1:2, by orifice ion gelation method with varying concentrations of calcium chloride. Six batches of microspheres (MS1 – MS6 were prepared. The microspheres were evaluated for various micromeritic properties and it was observed that all the batches exhibited free-flowing properties. Scanning electron microscopy results showed that the microspheres were almost spherical in shape and discrete. The FTIR results showed that there were no interactions between the drug and the excipients. The in vitro release profile indicated that all the batches of microspheres showed controlled and prolonged drug release over an extended period, with acceptable release kinetics. The work demonstrated that among all the formulations of microspheres, the microspheres of the formulation MS4 are promising candidates for the sustained release of pioglitazone hydrochloride.

  19. Pioglitazone halts axonal degeneration in a mouse model of X-linked adrenoleukodystrophy.

    Science.gov (United States)

    Morató, Laia; Galino, Jorge; Ruiz, Montserrat; Calingasan, Noel Ylagan; Starkov, Anatoly A; Dumont, Magali; Naudí, Alba; Martínez, Juan José; Aubourg, Patrick; Portero-Otín, Manuel; Pamplona, Reinald; Galea, Elena; Beal, M Flint; Ferrer, Isidre; Fourcade, Stéphane; Pujol, Aurora

    2013-08-01

    X-linked adrenoleukodystrophy is a neurometabolic disorder caused by inactivation of the peroxisomal ABCD1 transporter of very long-chain fatty acids. In mice, ABCD1 loss causes late onset axonal degeneration in the spinal cord in association with locomotor disability resembling the most common phenotype in patients, adrenomyeloneuropathy. Increasing evidence indicates that oxidative stress and bioenergetic failure play major roles in the pathogenesis of X-linked adrenoleukodystrophy. In this study, we aimed to evaluate whether mitochondrial biogenesis is affected in X-linked adrenoleukodystrophy. We demonstrated that Abcd1 null mice show reduced mitochondrial DNA concomitant with downregulation of mitochondrial biogenesis pathway driven by PGC-1α/PPARγ and reduced expression of mitochondrial proteins cytochrome c, NDUFB8 and VDAC. Moreover, we show that the oral administration of pioglitazone, an agonist of PPARγ, restored mitochondrial content and expression of master regulators of biogenesis, neutralized oxidative damage to proteins and DNA, and reversed bioenergetic failure in terms of ATP levels, NAD+/NADH ratios, pyruvate kinase and glutathione reductase activities. Most importantly, the treatment halted locomotor disability and axonal damage in X-linked adrenoleukodystrophy mice. These results lend support to the use of pioglitazone in clinical trials with patients with adrenomyeloneuropathy and reveal novel molecular mechanisms of action of pioglitazone in neurodegeneration. Future studies should address the effects of this anti-diabetic drug on other axonopathies in which oxidative stress and mitochondrial dysfunction are contributing factors.

  20. Pioglitazone and alogliptin combination therapy in type 2 diabetes: a pathophysiologically sound treatment.

    Science.gov (United States)

    Triplitt, Curtis; Cersosimo, Eugenio; DeFronzo, Ralph A

    2010-09-07

    Insulin resistance and islet (beta and alpha) cell dysfunction are major pathophysiologic abnormalities in type 2 diabetes mellitus (T2DM). Pioglitazone is a potent insulin sensitizer, improves pancreatic beta cell function and has been shown in several outcome trials to lower the risk of atherosclerotic and cardiovascular events. Glucagon-like peptide-1 deficiency/resistance contributes to islet cell dysfunction by impairing insulin secretion and increasing glucagon secretion. Dipeptidyl peptidase-4 (DPP-4) inhibitors improve pancreatic islet function by augmenting glucose-dependent insulin secretion and decreasing elevated plasma glucagon levels. Alogliptin is a new DPP-4 inhibitor that reduces glycosylated hemoglobin (HbA(1c)), is weight neutral, has an excellent safety profile, and can be used in combination with oral agents and insulin. Alogliptin has a low risk of hypoglycemia, and serious adverse events are uncommon. An alogliptin-pioglitazone combination is advantageous because it addresses both insulin resistance and islet dysfunction in T2DM. HbA(1c) reductions are significantly greater than with either monotherapy. This once-daily oral combination medication does not increase the risk of hypoglycemia, and tolerability and discontinuation rates do not differ significantly from either monotherapy. Importantly, measures of beta cell function and health are improved beyond that observed with either monotherapy, potentially improving durability of HbA(1c) reduction. The alogliptin-pioglitazone combination represents a pathophysiologically sound treatment of T2DM.

  1. Safety profiling of pioglitazone and telmisartan combination by sub-chronic toxicity study in rat.

    Science.gov (United States)

    Sengupta, Pinaki; Das, Arindam; Ibrahim, Fuzianna; Mandal, Uttam Kumar; Chatterjee, Bappaditya; Mahmood, Syed; Das, Sreemoy Kanti; Kifayatullah, Muhammad

    2016-11-01

    It has been reported that the major cause of mortality in diabetes is cardiovascular diseases and contribution of hypertension is significant in this context. Pioglitazone, a thiazolidinedione class of therapeutic agent is used to treat type 2 diabetes mellitus. Telmisartan, an angiotensin receptor blocker antihypertensive has been reported to have beneficial effect if co-administered with pioglitazone for the management of diabetes complications. The present research work aims to evaluate the safety/toxicity profile of this combination in rat model. The investigation was carried out after co-administering the drugs to the rats for 28 days at three dose levels of 50, 100 and 150 mg/kg covering low to high dose ranges. Various hematological and biochemical parameters were studied in addition to the histopathology of the major organs in order to evaluate the toxicity profile of the combination. Absence of mortality and histopathological changes as well as unaltered hematological and biochemical parameters was observed. This preliminary investigation concludes that the combination of pioglitazone and telmisartan can primarily be stated as safe in animals, even at the dose level which is several folds higher than the intended human dose. Thus, this combination can be explored in future to develop a rational therapy regimen to treat hypertensive diabetic patients.

  2. Imaging of a glucose analog, calcium and NADH in neurons and astrocytes: dynamic responses to depolarization and sensitivity to pioglitazone.

    Science.gov (United States)

    Pancani, Tristano; Anderson, Katie L; Porter, Nada M; Thibault, Olivier

    2011-12-01

    Neuronal Ca(2+) dyshomeostasis associated with cognitive impairment and mediated by changes in several Ca(2+) sources has been seen in animal models of both aging and diabetes. In the periphery, dysregulation of intracellular Ca(2+) signals may contribute to the development of insulin resistance. In the brain, while it is well-established that type 2 diabetes mellitus is a risk factor for the development of dementia in the elderly, it is not clear whether Ca(2+) dysregulation might also affect insulin sensitivity and glucose utilization. Here we present a combination of imaging techniques testing the disappearance of the fluorescent glucose analog 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) as an indication of glycolytic activity in neurons and astrocytes. Our work shows that glucose utilization at rest is greater in neurons compared to astrocytes, and ceases upon activation in neurons with little change in astrocytes. Pretreatment of hippocampal cultures with pioglitazone, a drug used in the treatment of type 2 diabetes, significantly reduced glycolytic activity in neurons and enhanced it in astrocytes. This series of experiments, including Fura-2 and NADH imaging, provides results that are consistent with the idea that Ca(2+) levels may rapidly alter glycolytic activity, and that downstream events beyond Ca(2+) dysregulation with aging, may alter cellular metabolism in the brain.

  3. Collateral blood vessels in acute ischemic stroke: a physiological window to predict future outcomes.

    Science.gov (United States)

    Alves, Heitor Castelo Branco Rodrigues; Pacheco, Felipe Torres; Rocha, Antonio J

    2016-08-01

    Collateral circulation is a physiologic pathway that protects the brain against ischemic injury and can potentially bypass the effect of a blocked artery, thereby influencing ischemic lesion size and growth. Several recent stroke trials have provided information about the role of collaterals in stroke pathophysiology, and collateral perfusion has been recognized to influence arterial recanalization, reperfusion, hemorrhagic transformation, and neurological outcomes after stroke. Our current aim is to summarize the anatomy and physiology of the collateral circulation and to present and discuss a comprehensible review of the related knowledge, particularly the effects of collateral circulation on the time course of ischemic injury and stroke severity, as well as imaging findings and therapeutic implications.

  4. The PPAR-γ agonist pioglitazone modulates inflammation and induces neuroprotection in parkinsonian monkeys

    Directory of Open Access Journals (Sweden)

    Swanson Christine R

    2011-08-01

    Full Text Available Abstract Background Activation of the peroxisome proliferator-activated receptor gamma (PPAR-γ has been proposed as a possible neuroprotective strategy to slow down the progression of early Parkinson's disease (PD. Here we report preclinical data on the use of the PPAR-γ agonist pioglitazone (Actos®; Takeda Pharmaceuticals Ltd. in a paradigm resembling early PD in nonhuman primates. Methods Rhesus monkeys that were trained to perform a battery of behavioral tests received a single intracarotid arterial injection of 20 ml of saline containing 3 mg of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP. Twenty-four hours later the monkeys were assessed using a clinical rating scale, matched accordingly to disability, randomly assigned to one of three groups [placebo (n = 5, 2.5 (n = 6 or 5 (n = 5 mg/kg of pioglitazone] and their treatments started. Three months after daily oral dosing, the animals were necropsied. Results We observed significant improvements in clinical rating score (P = 0.02 in the animals treated with 5 mg/kg compared to placebo. Behavioral recovery was associated with preservation of nigrostriatal dopaminergic markers, observed as higher tyrosine hydroxylase (TH putaminal optical density (P = 0.011, higher stereological cell counts of TH-ir (P = 0.02 and vesicular monoamine transporter-2 (VMAT-2-ir nigral neurons (P = 0.006. Stereological cell counts of Nissl stained nigral neurons confirmed neuroprotection (P = 0.017. Pioglitazone-treated monkeys also showed a dose-dependent modulation of CD68-ir inflammatory cells, that was significantly decreased for 5 mg/kg treated animals compared to placebo (P = 0.018. A separate experiment to assess CSF penetration of pioglitazone revealed that 5 mg/kg p.o. induced consistently higher levels than 2.5 mg/kg and 7.5 mg/kg. p.o. Conclusions Our results indicate that oral administration of pioglitazone is neuroprotective when administered early after inducing a

  5. The effects of the PPAR-gamma gonist pioglitazone on plasma concentrations of circulating vasoactive factors in type II diabetes mellitus

    NARCIS (Netherlands)

    de Boer, R. A.; Martens, F. M. A. C.; Kuipers, I.; Boomsma, F.; Visseren, F. L. J.

    2010-01-01

    The use of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist pioglitazone, which is registered as an oral antidiabetic drug, has consistently been associated with a decrease in blood pressure (BP) of about 3-5 mm Hg. The present study evaluates the effects of pioglitazone tre

  6. Effect of pioglitazone on muscle sympathetic nerve activity in type 2 diabetes mellitus with α-glucosidase inhibitor.

    Science.gov (United States)

    Kobayashi, Daisuke; Takamura, Masayuki; Murai, Hisayoshi; Usui, Soichiro; Ikeda, Tatsunori; Inomata, Jun-ichiro; Takashima, Shin-ichiro; Kato, Takeshi; Furusho, Hiroshi; Takeshita, Yumie; Ota, Tsuguhito; Takamura, Toshinari; Kaneko, Shuichi

    2010-12-08

    Activation of the sympathetic nervous system is augmented in patients with type 2 diabetes mellitus (DM). Pioglitazone, an anti-diabetic drug, improves insulin resistance, but its influence on sympathetic nerve activity is not clear. To identify the relationship between insulin resistance and sympathetic activity, we examined muscle sympathetic nerve activity (MSNA) in controlled type 2 DM patients with alpha-glucosidase inhibitor (GI). We measured MSNA and calculated homeostasis model assessment of insulin resistance index (HOMA-IR) in twelve DM patients treated with alpha-GI and thirteen age-matched healthy subjects. In DM patients with alpha-GI, all parameters were reexamined after three months of treatment with pioglitazone. MSNA and HOMA-IR were significantly greater in DM patients with alpha-GI compared to healthy subjects. Hemoglobin A1c did not differ in DM patients before and after pioglitazone. However, pioglitazone significantly decreased MSNA in DM patients compared with alpha-GI (21.7±5.2 vs. 32.0±6.8 burst/min, ppioglitazone was similar to that in healthy subjects. HOMA-IR significantly decreased after pioglitazone, and a significant relationship was found between the absolute change in MSNA and HOMA-IR (r=0.65, ppioglitazone provides an additional effect on inhibition of sympathetic nerve activity.

  7. Gender differences in non-glycemic responses to improved insulin sensitivity by pioglitazone treatment in patients with type 2 diabetes.

    Science.gov (United States)

    Arnetz, Lisa; Dorkhan, Mozhgan; Alvarsson, Michael; Brismar, Kerstin; Ekberg, Neda Rajamand

    2014-04-01

    Excess cortisol and GH induce insulin resistance, a central feature of type 2 diabetes (T2D). To study whether the insulin sensitizer pioglitazone affects basal cortisol levels and the GH-IGF-I axis in patients with T2D. Forty-eight patients with T2D (men/women = 28:20, age 61 ± 1 years, BMI 31 ± 0.6 kg/m(2)) were treated for 26 weeks with pioglitazone 30-45 mg daily in addition to their preexisting therapy. Insulin, proinsulin, HbA(1c), IGF-I, IGFBP-1, and basal cortisol were analyzed before and after treatment. Pioglitazone decreased proinsulin/insulin ratio and HbA(1c) decreased (HbA(1c) from 7.8 ± 0.2 to 6.6 ± 0.2% in men and from 7.6 ± 0.2 to 6.1 ± 0.2% in women, p pioglitazone increased IGF-I regardless of gender and in women also increased basal cortisol. Increased IGF-I may contribute to improved insulin sensitivity after treatment. There seems to be gender differences in treatment responses to pioglitazone on lipid metabolism and basal cortisol, perhaps correcting different mechanisms of insulin resistance between genders.

  8. Determinants of leptomeningeal collateral flow in stroke patients with a middle cerebral artery occlusion

    Energy Technology Data Exchange (ETDEWEB)

    Seeters, Tom van; Velthuis, Birgitta K. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Biessels, Geert Jan; Kappelle, L.J. [University Medical Center Utrecht, Department of Neurology, Brain Center Rudolf Magnus, Utrecht (Netherlands); Graaf, Yolanda van der [University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht (Netherlands); Collaboration: on behalf of the Dutch acute stroke study (DUST) investigators

    2016-10-15

    Poor leptomeningeal collateral flow is related to worse clinical outcome in acute ischemic stroke, but the factors that determine leptomeningeal collateral patency are largely unknown. We explored the determinants of leptomeningeal collateral flow and assessed their effect on the relation between leptomeningeal collateral flow and clinical outcome. We included 484 patients from the Dutch acute stroke study (DUST) with a middle cerebral artery (MCA) occlusion. The determinants of poor leptomeningeal collateral flow (≤50 % collateral filling) were identified with logistic regression. We calculated the relative risk (RR) of poor leptomeningeal collateral flow in relation to poor clinical outcome (90-day modified Rankin Scale 3-6) using Poisson regression and assessed whether the determinants of leptomeningeal collateral flow affected this relation. Leptomeningeal collateral flow was poor in 142 patients (29 %). In multivariable analyses, higher admission glucose level (odds ratio (OR) 1.1 per mmol/L increase (95 % CI 1.0-1.2)), a proximal MCA occlusion (OR 1.9 (95 % CI 1.3-3.0)), and an incomplete posterior circle of Willis (OR 1.7 (95 % CI 1.1-2.6)) were independently related to poor leptomeningeal collateral flow. Poor leptomeningeal collateral flow was related to poor clinical outcome (unadjusted RR 1.7 (95 % CI 1.4-2.0)), and this relation was not affected by the determinants of leptomeningeal collateral flow. Our study shows that admission glucose level, a proximal MCA occlusion, and an incomplete ipsilateral posterior circle of Willis are determinants of leptomeningeal collateral flow that represent a combination of congenital, acquired, and acute factors. After adjustment for these determinants, leptomeningeal collateral flow remains related to clinical outcome. (orig.)

  9. Low dose pioglitazone does not affect bone formation and resorption markers or bone mineral density in streptozocin-induced diabetic rats.

    Science.gov (United States)

    Tsirella, E; Mavrakanas, T; Rager, O; Tsartsalis, S; Kallaras, K; Kokkas, B; Mironidou-Tzouveleki, M

    2012-04-01

    Our study aims to investigate the effect of a low-dose pioglitazone regimen on bone mineral density and bone formation-resorption markers in control and diabetic rats. Wistar rats were divided into 4 groups: non-diabetic controls, control rats receiving pioglitazone (3 mg/kg), streptozocin-treated diabetic rats (50 mg/kg), diabetic rats treated with pioglitazone (3 mg/kg). The duration of the experiment was 8 weeks. Diabetes in our rats was associated with weight loss, increased urinary calcium excretion and reduced plasma osteocalcin levels. Diabetes mellitus did not affect bone mineral density. Pioglitazone administration had no impact on bone formation and resorption markers levels and did not modify bone mineral density in the four studied groups. Pioglitazone at the 3 mg/kg dose was not associated with significant skeletal complications in our experimental model.

  10. Anti-pruritic activity of pioglitazone on serotonin-induced scratching in mice: possible involvement of PPAR-gamma receptor and nitric oxide.

    Science.gov (United States)

    Shafizadeh, Milad; Rajaba, Armin; Imran khan, Muhammad; Ostadhadi, Sattar; Rastegar, Hosein; Dehpour, Ahmadreza

    2014-12-05

    Pioglitazone is a member of peroxisome proliferator-activated receptor gamma (PPARγ) agonists, particularly used in management of type II diabetes. However it also has effects in some dermatological disorders. The current study was designed to investigate the effects of oral administration of pioglitazone and the association of nitric oxide, in serotonin-induced scratching in mice. In order to produce the scratching activity, serotonin (141 nm/site) was administered intradermally in the nape of the neck. Pioglitazone in concentrations of 10, 20, 40 and 80 mg/kg, was peroral administered (p.o) as a single dose, 4 h before the serotonin injection. PPAR-γ antagonist, GW9662 (2 mg/kg, i.p); a non-specific nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 1 mg/kg, i.p); or a nitric oxide precursor, L-arginine (100 mg/kg, i.p.); adminstrated 15 min before pioglitazone were analyzed for anti-scratching activity. Results obtained showed that pioglitazone (40 and 80 mg/kg, p.o) reduced the scratching in a dose-dependent manner. GW9662 inverted the anti-scratching effect of pioglitazone (80 mg/kg). Acute dose of L-NAME (1 mg/kg, i.p) also prevented the anti-scratching property of pioglitazone (80 mg/kg, p.o); although L-arginine was used in sub-effective dose (100 mg/kg, i.p), however it potentiated the anti-scratching behavior when co-injected with pioglitazone (20 mg/kg, p.o). The results indicate that acute pioglitazone has an anti-scratching effect on serotonin-induced scratching in mice. It is concluded that anti-scratching outcome of acute pioglitazone is initiated via activation of PPAR-γ receptor and to some extent by the NO pathway.

  11. Collateral Lethality: A new therapeutic strategy in oncology.

    Science.gov (United States)

    Muller, Florian L; Aquilanti, Elisa A; DePinho, Ronald A

    2015-11-01

    Genomic deletion of tumor suppressor genes (TSG) is a rite of passage for virtually all human cancers. The synthetic lethal paradigm has provided a framework for the development of molecular targeted therapeutics that are functionally linked to the loss of specific TSG functions. In the course of genomic events that delete TSGs, a large number of genes with no apparent direct role in tumor promotion also sustain deletion as a result of chromosomal proximity to the target TSG. In this perspective, we review the novel concept of "collateral lethality", which has served to identify cancer-specific therapeutic vulnerabilities resulting from co-deletion of passenger genes neighboring TSG. The large number of collaterally deleted genes, playing diverse functions in cell homeostasis, offers a rich repertoire of pharmacologically targetable vulnerabilities presenting novel opportunities for the development of personalized anti-neoplastic therapies.

  12. Anti-diabetic properties of a non-conventional radical scavenger, as compared to pioglitazone and exendin-4, in streptozotocin-nicotinamide diabetic mice.

    Science.gov (United States)

    Novelli, Michela; Canistro, Donatella; Martano, Manuela; Funel, Niccola; Sapone, Andrea; Melega, Simone; Masini, Matilde; De Tata, Vincenzo; Pippa, Anna; Vecoli, Cecilia; Campani, Daniela; De Siena, Rocco; Soleti, Antonio; Paolini, Moreno; Masiello, Pellegrino

    2014-04-15

    We previously showed that the innovative radical scavenger bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate (IAC) improves metabolic dysfunctions in a diabetic mouse model. Here, we compared the in vivo effects of IAC with those of the anti-diabetic drugs pioglitazone (PIO) and exendin-4 (EX-4). Diabetes was induced in C57Bl/6J mice by streptozotocin and nicotinamide administration. Paralleled by healthy controls, diabetic animals (D) were randomly assigned to four groups and treated daily for 7 consecutive weeks: D+saline, ip; D+IAC 30mg/kgb.w., ip; D+PIO 10mg/kgb.w. per os; and D+EX-4, 50μg/kgb.w., ip. Our results show that IAC reduced basal hyperglycemia and improved glucose tolerance better than PIO or EX-4. Interestingly, in the heart of diabetic mice, IAC treatment normalized the increased levels of GSSG/GSH ratio and thiobarbituric acid reactive substances, indexes of oxidative stress and damage, while PIO and EX-4 were less effective. As supported by immunohistochemical data, IAC markedly prevented diabetic islet β-cell reduced density, differently from PIO and EX-4 that had only a moderate effect. Interestingly, in diabetic animals, IAC treatment enhanced the activity of pancreatic-duodenal homeobox 1 (PDX-1), an oxidative stress-sensitive transcription factor essential for maintenance of β-cell function, as evaluated by quantification of its nuclear immunostaining, whereas PIO or EX-4 treatments did not. Altogether, these observations support the improvement of the general redox balance and β-cell function induced by IAC treatment in streptozotocin-nicotinamide diabetic mice. Furthermore, in this model, the correction of diabetic alterations was better obtained by treatment with the radical scavenger IAC than with pioglitazone or exendin-4.

  13. Potentiation of indomethacin-induced anti-inflammatory response by pioglitazone in carrageenan-induced acute inflammation in rats: Role of PPARγ receptors.

    Science.gov (United States)

    Houshmand, Gholamreza; Mansouri, Mohammad Taghi; Naghizadeh, Bahareh; Hemmati, Ali Asghar; Hashemitabar, Mahmoud

    2016-09-01

    This study aimed to assess the interaction between anti-inflammatory effects of pioglitazone (peroxysome proliferator activated receptor-gamma (PPARγ) agonist, PGL), and indomethacin (cyclooxygenase (COX) inhibitor, IND) and to evaluate the possible underlying mechanisms. Paw edema induced by carrageenan was used to induce inflammation. Different doses of IND (0.3-10mg/kg) and PGL (1-20mg/kg) alone or in combination were administered intraperitoneally to rats. Paw tissue levels of PPARγ, COX-2, and prostaglandin E2 and serum levels of TNF-α and IL-10 were also estimated. Doses of IND and PGL showed a statistically significant anti-inflammatory effect. Combination of a non-effective dose of IND (0.3mg/kg) with increasing doses of PGL (1-10mg/kg) resulted in potentiated anti-inflammation and vise versa. IND, PGL and the combination were able to reduce the COX-2, PGE2 contents and TNF-α level. Moreover, all these treatments caused elevation in PPARγ levels and IL-10 levels. However, when the rats were pre-treated with GW-9662 (a selective PPARγ antagonist), all the anti-inflammation and alterations in the biochemical factors were antagonized. These results showed that PGL markedly enhanced the anti-inflammatory activity of IND and this effect mediated partly at least, through PPARγ. Possible mechanisms of the interaction were that PGL stimulates the PPARγ and inhibits COX-2 by those cytokines that trigger the PPARγ and also inhibit COX-2. This study suggests that combination therapy with pioglitazone and indomethacin may provide an alternative for the clinical control of inflammation especially in patients with diabetes.

  14. The peroxisome proliferator-activated receptor-γ agonist pioglitazone protects against cisplatin-induced renal damage in mice.

    Science.gov (United States)

    Jesse, Cristiano R; Bortolatto, Cristiani F; Wilhelm, Ethel A; Roman, Silvane Souza; Prigol, Marina; Nogueira, Cristina W

    2014-01-01

    Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists not only improve metabolic abnormalities of diabetes and consequent diabetic nephropathy, but they also protect against non-diabetic kidney disease in experimental models. Here, we investigated the effect of PPAR-γ agonist pioglitazone against acute renal injury on a cisplatin model in mice. Nephrotoxicity was induced by a single intraperitoneal (i.p.) injection of cisplatin (10 mg kg(-1)). Pioglitazone was administered for six consecutive days in doses of 15 or 30 mg kg(-1)  day(-1), per os (p.o.), starting 3 days before cisplatin injection. Cisplatin treatment to mice induced a marked renal failure, characterized by a significant increase in serum urea and creatinine levels and alterations in renal tissue architecture. Cisplatin exposure induced oxidative stress as indicated by decreased levels of non-enzymatic antioxidant defenses [glutathione (GSH) and ascorbic acid levels] and components of the enzymatic antioxidant defenses [superoxide dismutase (SOD), catalase (CAT) glutathione peroxidase (GPx), glutathione reductase (GR) and and glutathione S-transferase(GST) activities)] in renal tissue. Administration of pioglitazone markedly protected against the increase in urea and creatinine levels and histological alterations in kidney induced by cisplatin treatment. Pioglitazone administration ameliorated GSH and ascorbic acid levels decreased by cisplatin exposure in mice. Pioglitazone protected against the inhibition of CAT, SOD, GPx, GR and GST activities induced by cisplatin in the kidneys of mice. These results indicated that pioglitazone has a protective effect against cisplatin-induced renal damage in mice. The protection is mediated by preventing the decline of antioxidant status. The results have implications in use of PPAR-γ agonists in human application for protecting against drugs-induced nephrotoxicity.

  15. HPLC-DAD Method for the Pharmacokinetic Interaction Study of Atorvastatin with Pioglitazone and Cholestyramine in Wistar Rats.

    Science.gov (United States)

    Sharma, Ritesh N; Pancholi, Shyam S

    2014-01-01

    Carotid intima-media thickness is used as a surrogate marker for cardiovascular complications in diabetes mellitus. The combination of atorvastatin and pioglitazone was found to be effective in reducing the thickness of the carotid intima-media layer. The method of RP-HPLC coupled with a diode array detector (DAD) was developed for the pharmacokinetic interaction study of atorvastatin with pioglitazone and cholestyramine, respectively, in Wistar rats. Atorvastatin (ATR) and pioglitazone (PIO) were resolved on a C18 column with a mobile phase composed of 48% methanol, 19% acetonitrile, and 33% 10 mM ammonium formate (v/v/v; pH 3.5±0.3, by formic acid) and a 260 nm detection wavelength on the diode array detector. The method was validated according to international standards with good reproducibility and linear response; mean (r) 0.9987 and 0.9972 to ATR and PIO, respectively. The coefficients of variation of intra- and interassay precision ranged between 4.95-8.12 and 7.29-9.67, respectively. Pharmacokinetic parameters were determined in rats following an oral administration of atorvastatin in the presence and absence of pioglitazone and also with cholestyramine. Compared with the control given atorvastatin alone, the Cmax and AUC of atorvastatin were merely unchanged in rats with the co-administration of pioglitazone, while they decreased by nearly 21 and 15%, respectively, with the concurrent use of cholestyramine. There were no significant changes in Tmax and the plasma half-life (T1/2 ) of atorvastatin in both cases. The performed experiment demonstrated that the presented method was suitable for the estimation and pharmacokinetic interaction study of atorvastatin with pioglitazone and cholestyramine in Wistar rat plasma.

  16. Pioglitazone inhibits the expression of matrix metalloproteinase-9, a protein involved in diabetes-associated wound healing.

    Science.gov (United States)

    Zhang, Jun; Huang, Xiaoyuan; Wang, Lingfeng

    2014-08-01

    Matrix metalloproteinase-9 (MMP-9) is a protein involved in diabetes-associated wound healing. The present study aimed to determine whether pioglitazone, an agonist of peroxisome proliferator-activated receptor‑γ (PPAR-γ), inhibits the expression of MMP-9. HaCaT cells at a density of 6x105 cells/well were seeded into 6-well plates in medium and were cultured for 24 h. The cells were then treated with bovine serum albumin (BSA) only or advanced glycation end‑product (AGE)-BSA (50, 100, 200, 300 or 400 µg/ml), with or without pioglitazone (0.5 or 1 µM). The effects of AGE-BSA on cell viability were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The levels of MMP-9 secreted into the medium were detected by an enzyme-linked immunosorbent assay. The mRNA and protein levels were analyzed by quantitative polymerase chain reaction (qPCR) and western blot analysis, respectively. AGEs are able to increase the level of MMP-9 mRNA in HaCaT cells and the levels of MMP-9 protein secreted into the medium. Pioglitazone (0.5 or 1 µΜ) significantly inhibited the levels of MMP-9 in the treated HaCaT cells. Pioglitazone (0.5 or 1 µΜ) also suppressed the levels of MMP-9 in the cell culture medium. Pioglitazone at concentrations of 0.5 and 1 µΜ significantly suppressed the levels of MMP-9 mRNA to 20 or 8%, respectively. These results suggest that pioglitazone is able to effectively suppress the expression of MMP-9 via a transcriptional mechanism.

  17. Pioglitazone ameliorates memory deficits in streptozotocin-induced diabetic mice by reducing brain β-amyloid through PPARY activation

    Institute of Scientific and Technical Information of China (English)

    Li-ping LIU; Tian-hua YAN; Li-ying JIANG; Wei HU; Meng HU; Chao WANG; Qian ZHANG

    2013-01-01

    Aim:To examine the effects of pioglitazone,a PPARY agonist,on memory performance and brain amyloidogenesis in streptozotocin (STZ)-induced diabetic mice.Methods:ICR male mice were injected with STZ (150 mg/kg,iv) to induce experimental diabetes.Pioglitazone (9 and 18 mg·kg1-d-1,po) was administered for 6 weeks.Passive avoidance and Morris water maze (MWM) tests were used to evaluate cognitive function.The blood glucose and serum insulin levels were detected using the glucose oxidase method and an ELISA assay,respectively.β-amyloid (Aβ),β-amyloid precursor protein (APP),β-amyloid precursor protein cleaving enzyme 1 (BACE1),NF-κB p65,the receptor for advanced glycation end products (RAGE) and PPARy in the brains were analyzed using Western blotting assays.Results:The STZ-induced diabetic mice characterized by hyperglycemia and hypoinsulinemia performed poorly in both the passive avoidance and MWM tests,accompanied by increased Aβ1-40/Aβ1-42,APP,BACE1,NF-κB p65 and RAGE levels and decreased PPARy level in the hippocampus and cortex.Chronic pioglitazone treatment significantly ameliorated the memory deficits of STZ-induced diabetic mice,and suppressed expression of APP,BACE1,RAGE and NF-κB p65,and activated PPARy in the hippocampus and cortex.However,pioglitazone did not significantly affect blood glucose and insulin levels.Conclusion:Pioglitazone ameliorates memory deficits in STZ-induced diabetic mice by reducing brain Aβ level via activation of PPARy,which is independent of its effects on blood glucose and insulin levels.The results suggest that pioglitazone may be used for treating the cognitive dysfunction in type 1 diabetes mellitus.

  18. Collateral flow averts hemorrhagic transformation after endovascular therapy for acute ischemic stroke.

    Science.gov (United States)

    Bang, Oh Young; Saver, Jeffrey L; Kim, Suk Jae; Kim, Gyeong-Moon; Chung, Chin-Sang; Ovbiagele, Bruce; Lee, Kwang Ho; Liebeskind, David S

    2011-08-01

    Collaterals sustain the ischemic penumbra to limit growth of the infarct core before revascularization, yet the impact of baseline collateral flow on hemorrhagic transformation (HT) after endovascular therapy remains unknown. A collaborative study from 2 stroke centers in distinct geographic regions included 222 consecutive patients who received endovascular therapy for acute cerebral ischemia. The influence of collaterals on HT was analyzed in distinct case scenarios relative to baseline collateral grade at angiography (0 to 1 versus 2 to 4) and recanalization (Thrombolysis in Myocardial Ischemia scale, 0 to 1 versus 2 to 3): good collaterals and successful recanalization (n=98), poor collaterals with successful recanalization (n=43), good collaterals and no recanalization(n=46), and poor collaterals and no recanalization (n=35). HT after endovascular therapy occurred in 103 (46.4%) patients; 42 (18.9%) were symptomatic. HT was more frequently observed in patients with poor collaterals and recanalization than in other groups (P=0.048). When revascularization was achieved, patients with poorer collaterals were more likely to have symptomatic worsening with HT (r=-0.181, P=0.032). Multiple logistic regression analysis identified aggressive treatment (OR, 2.558 for Merci clot retrieval; 95% CI, 1.153 to 5.678; OR, 3.618 for combined fibrinolytics and mechanical therapy; 95% CI, 1.551 to 8.437; and OR, 2.085 for intravenous thrombolysis before endovascular therapy; 95% CI, 1.096 to 3.969), poor collaterals and recanalization (OR, 2.666; 95% CI, 1.163 to 6.113), and serum glucose levels (OR, 1.007; 95% CI, 1.000 to 1.014) as independent predictors of HT. Angiographic grade of collateral flow strongly influences the rate of HT after therapeutic recanalization for acute ischemic stroke. Collateral status readily available from baseline angiography may therefore refine therapeutic decision-making in acute cerebral ischemia.

  19. The effect of pioglitazone and resistance training on body composition in older men and women undergoing hypocaloric weight loss.

    Science.gov (United States)

    Shea, M Kyla; Nicklas, Barbara J; Marsh, Anthony P; Houston, Denise K; Miller, Gary D; Isom, Scott; Miller, Michael E; Carr, J Jeffrey; Lyles, Mary F; Harris, Tamara B; Kritchevsky, Stephen B

    2011-08-01

    Age-related increases in ectopic fat accumulation are associated with greater risk for metabolic and cardiovascular diseases, and physical disability. Reducing skeletal muscle fat and preserving lean tissue are associated with improved physical function in older adults. PPARγ-agonist treatment decreases abdominal visceral adipose tissue (VAT) and resistance training preserves lean tissue, but their effect on ectopic fat depots in nondiabetic overweight adults is unclear. We examined the influence of pioglitazone and resistance training on body composition in older (65-79 years) nondiabetic overweight/obese men (n = 48, BMI = 32.3 ± 3.8 kg/m(2)) and women (n = 40, BMI = 33.3 ± 4.9 kg/m(2)) during weight loss. All participants underwent a 16-week hypocaloric weight-loss program and were randomized to receive pioglitazone (30 mg/day) or no pioglitazone with or without resistance training, following a 2 × 2 factorial design. Regional body composition was measured at baseline and follow-up using computed tomography (CT). Lean mass was measured using dual X-ray absorptiometry. Men lost 6.6% and women lost 6.5% of initial body mass. The percent of fat loss varied across individual compartments. Men who were given pioglitazone lost more visceral abdominal fat than men who were not given pioglitazone (-1,160 vs. -647 cm(3), P = 0.007). Women who were given pioglitazone lost less thigh subcutaneous fat (-104 vs. -298 cm(3), P = 0.002). Pioglitazone did not affect any other outcomes. Resistance training diminished thigh muscle loss in men and women (resistance training vs. no resistance training men: -43 vs. -88 cm(3), P = 0.005; women: -34 vs. -59 cm(3), P = 0.04). In overweight/obese older men undergoing weight loss, pioglitazone increased visceral fat loss and resistance training reduced skeletal muscle loss. Additional studies are needed to clarify the observed gender differences and evaluate how these changes in body composition influence functional status.

  20. Cardiac Outcomes After Ischemic Stroke or Transient Ischemic Attack: Effects of Pioglitazone in Patients With Insulin Resistance Without Diabetes Mellitus.

    Science.gov (United States)

    Young, Lawrence H; Viscoli, Catherine M; Curtis, Jeptha P; Inzucchi, Silvio E; Schwartz, Gregory G; Lovejoy, Anne M; Furie, Karen L; Gorman, Mark J; Conwit, Robin; Abbott, J Dawn; Jacoby, Daniel L; Kolansky, Daniel M; Pfau, Steven E; Ling, Frederick S; Kernan, Walter N

    2017-05-16

    Insulin resistance is highly prevalent among patients with atherosclerosis and is associated with an increased risk for myocardial infarction (MI) and stroke. The IRIS trial (Insulin Resistance Intervention after Stroke) demonstrated that pioglitazone decreased the composite risk for fatal or nonfatal stroke and MI in patients with insulin resistance without diabetes mellitus, after a recent ischemic stroke or transient ischemic attack. The type and severity of cardiac events in this population and the impact of pioglitazone on these events have not been described. We performed a secondary analysis of the effects of pioglitazone, in comparison with placebo, on acute coronary syndromes (MI and unstable angina) among IRIS participants. All potential acute coronary syndrome episodes were adjudicated in a blinded fashion by an independent clinical events committee. The study cohort was composed of 3876 IRIS participants, mean age 63 years, 65% male, 89% white race, and 12% with a history of coronary artery disease. Over a median follow-up of 4.8 years, there were 225 acute coronary syndrome events, including 141 MIs and 84 episodes of unstable angina. The MIs included 28 (19%) with ST-segment elevation. The majority of MIs were type 1 (94, 65%), followed by type 2 (45, 32%). Serum troponin was 10× to 100× upper limit of normal in 49 (35%) and >100× upper limit of normal in 39 (28%). Pioglitazone reduced the risk of acute coronary syndrome (hazard ratio, 0.71; 95% confidence interval, 0.54-0.94; P=0.02). Pioglitazone also reduced the risk of type 1 MI (hazard ratio, 0.62; 95% confidence interval, 0.40-0.96; log-rank P=0.03), but not type 2 MI (hazard ratio, 1.05; 95% confidence interval, 0.58-1.91; P=0.87). Similarly, pioglitazone reduced the risk of large MIs with serum troponin >100× upper limit of normal (hazard ratio, 0.44; 95% confidence interval, 0.22-0.87; P=0.02), but not smaller MIs. Among patients with insulin resistance without diabetes mellitus

  1. Formulation and development of self-microemulsifying drug delivery system of pioglitazone hydrochloride

    Directory of Open Access Journals (Sweden)

    Jyotsana R. Madan

    2014-01-01

    Full Text Available Self-microemulsifying drug delivery system (SMEDDS is a promising system for the Biopharmaceutics Classification System (BCS class II drugs. The current research aimed to improve the dissolution of poorly water-soluble antidiabetic drug pioglitazone HCl by formulating it in SMEDDS. Liquid SMEDDS of pioglitazone HCl were formulated with Capmul MCM C8 and oleic acid as oil phase, Cremophor RH 40 and Tween 80 as surfactant phase, and Transcutol P as cosurfactant phase after screening various vehicles. The prepared formulations were evaluated for self-emulsifying ability and phase diagram was constructed to optimize the system. These systems were further characterized for globule size, effect of pH and robustness, zeta potential, drug content, viscosity, self-emulsification time, polydispersity index, % transmittance, thermodynamic stability, surface morphology, and drug release. The system was robust to different pH media and dilution volumes. The optimized system possessed a mean globule size of 122.2 nm, zeta potential around -22.9 mV, drug content 99.66 ± 0.47%, viscosity 0.8874 ± 0.026 cP, emulsification time 38 s, polydispersity index value of 0.5, and transmittance value of 99.3 ± 0.6%. Drug release in hydrochloric acid buffer pH 2 was found to be 99.35 ± 0.38%. More than three-fold increase in dissolution characteristics of pioglitazone HCl in SMEDDS was observed as compared to pure and marketed formulation. Liquid SMEDDS filled in hard gelatin capsule (HGC shell was found to be compatible. Stability studies show there was no sign of phase separation or precipitation and no change in drug content was observed.

  2. FGF-4 gene therapy GENERX--Collateral Therapeutics.

    Science.gov (United States)

    2002-01-01

    Collateral Therapeutics and Schering AG in Germany are developing a gene therapy product, GENERX for coronary artery disease. Based on the terms of the agreement, Schering or its affliates will be responsible for conducting and financing phase II/III clinical trials which are currently underway in the US and Europe. In particular, Berlex Labs (the US subsidiary of Schering AG), is involved in developing the gene therapy in the US. GENERX is an angiogenic gene therapy which triggers the production of a protein that stimulates new blood vessel growth providing an alternative route for blood to bypass clogged and blocked arteries in the heart. GENERX involves a one-time, non-surgical delivery of an adenovirus vector containing the human fibroblast growth factor-4 (FGF-4) into coronary arteries via a standard catheter. The FGF-4 gene was licensed from New York University. Collateral Therapeutics has been granted a US patent for "gene transfer-mediated angiogenesis therapy" for the nonsurgical administration of angiogenic genes for coronary and peripheral vascular disease. The patented technology has been licensed from the University of California. Collateral and Berlex have initiated pivotal phase IIb/III trials with GENERX in the US and Europe. The US-based study will evaluate the safety and efficacy of GENERX in patients with stable exertional angina due to coronary artery disease. The European-based study will evaluate patients with advanced coronary artery disease who are not considered candidates for interventions such as angioplasty and bypass surgery and/or patients who are unlikely to have positive outcomes from such interventions. Both studies, of a multicentre, randomised, double-blind and placebo-controlled design, will evaluate 2 dose levels of GENERX which will be non-surgically administered to the heart via intracoronary infusion through a standard cardiac catheter. Collateral also plans to develop a non-surgical gene therapy product using the FGF-4 gene

  3. [Analysis of the meridian-collateral theoretical framework and the conceptual annotation of YANG Shangshan].

    Science.gov (United States)

    Zhang, Jianbin

    2016-02-01

    When classifying and compiling Huangdi Neijing (The Yellow Emperor's Inner Classic), YANG Shangshan had constructed the systematic framework of the meridian-collateral theory. It has been found in the investigation of Huangdi Neijing Taisu (Grand Simplicity of The Yellow Emperor's Inner Classic) that YANG Shangshan constructed the meridian-collateral systematic framework on the foundation of meridian theory. This framework includes two parts. One is the twelve meridians and the other one is the eight extra meridians, in which, the divergent meridians are derived from the regular meridians, and the collaterals, the cutaneous regions of meridians, genjie and biaoben are attributive to the regular meridians. The theory of the jingjin of meridians should be different from meridian-collateral system. YANG Shangshan constructed and annotated the meridian-collateral system, interpreting his unique thinking and analytic foundation. Being one of the forms of meridian-collateral theory at the early stage, YANG Shangshan's discovery deserves to be considered.

  4. [Science of Meridians, Collaterals and Acupoints--Exploration on teaching method of meridian syndromes].

    Science.gov (United States)

    Wang, Yinping; Zhang, Zongquan; Wang, Wenlin; Yuan, Limin

    2015-04-01

    Meridian syndromes are the required basic knowledge for mastering Science of Meridians, Collaterals and Acupoints but have not brought the adequate attention on the teaching program. The writers discovered' that the content of this section occupied a decisive role for developing the students' clinical thinking ability and, stimulating their interests to learn classical TCM theories. It's necessary to enhance the importance on meridian syndromes during teaching program. The teaching program was discussed in three aspects, named workshop pattern, competitive pattern and multimedia pattern. This teaching method may improve students' interests in the study on classical TCM theories, deepen the understanding on knowledge and motivate students' learning autonomy so that the teaching quality can be improved.

  5. Effect of pioglitazone on in-stent restenosis after coronary drug-eluting stent implantation: a meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Ming-duo Zhang

    Full Text Available In-stent restenosis (ISR remains a common life-threatening complication and some studies have shown that pioglitazone can reduce the incidence of ISR in patients with drug-eluting stents (DES implantation. We conducted a meta-analysis to assess the effect of pioglitazone in preventing ISR after DES implantation.Randomized controlled trials (RCTs investigating the effects of pioglitazone for ISR after DES implantation were identified by systematic searches of multiple online databases and manual searches of related reference lists of identified trials through May 2014. The primary endpoint was the rate of ISR. Secondary endpoints included minimum lumen diameter, percentage stenosis of stented vessels, late loss, in-stent neointimal volume, target vessel revascularization (TVR, target lesion revascularization, myocardial infarction, stent thrombosis and death.Five studies, comprising 255 pioglitazone-treated patients and 245 controls, were identified in the current meta-analysis. Pioglitazone did not significantly reduce the rate of ISR (P = 0.20 with low heterogeneity (I2 = 13.3%, P = 0.32. For the secondary outcomes, pioglitazone did not substantially affect the pooled estimates of these endpoints except late loss (P = 0.01 and TVR (P = 0.04.The limited evidence indicates that pioglitazone does not demonstrate markedly beneficial effect in patients subjected to coronary DES implantation. However, the results should be interpreted with care given the small sample size. Further large-scale RCTs are needed.

  6. Risk of bladder cancer among patients with diabetes treated with a 15 mg pioglitazone dose in Korea: a multi-center retrospective cohort study.

    Science.gov (United States)

    Jin, Sang-Man; Song, Sun Ok; Jung, Chang Hee; Chang, Jin-Sun; Suh, Sunghwan; Kang, Seung Min; Jung, Inkyung; Park, Cheol-Young; Kim, Jae Hyeon; Cho, Jae Hyoung; Lee, Byung-Wan

    2014-02-01

    It has not yet been determined whether chronic exposure to relatively low doses of pioglitazone increases risk of bladder cancer. We aimed to assess the risk of bladder cancer associated with pioglitazone in Korean patients. This was a retrospective cohort study of diabetic patients who had ≥ 2 clinic visits between November 2005 and June 2011 at one of four tertiary referral hospitals in Korea. A prevalent case-control analysis nested within the cohort was conducted to further adjust confounders. A total of 101,953 control patients and 11,240 pioglitazone-treated patients were included, in which there were 237 and 30 cases of incidental bladder cancer (64.9 and 54.9 per 100,000 person-years; age, sex-adjusted HR 1.135, 95% confidence interval [CI] 0.769-1.677), respectively. In the prevalent case-control analysis nested within the cohort, use of pioglitazone for a duration of > 6 months, but not ever use of pioglitazone, was associated with an increased rate of bladder cancer as compared to never use of pioglitazone. In conclusion, we failed to exclude the possible association between use of pioglitazone for a duration of > 6 months and bladder cancer.

  7. Comparison of metabolic profile and adiponectin level with pioglitazone versus voglibose in patients with type-2 diabetes mellitus associated with metabolic syndrome.

    Science.gov (United States)

    Fujitaka, Keisuke; Otani, Hajime; Jo, Fusakazu; Jo, Hiromi; Nomura, Emiko; Iwasaki, Masayoshi; Nishikawa, Mitsushige; Iwasaka, Toshiji

    2011-01-01

    Type 2 diabetes mellitus (T2DM) associated with metabolic syndrome (MetS) represents a high risk of cardiovascular disease. We compared the effect of early intervention with pioglitazone versus voglibose on physical and metabolic profiles and serum adiponectin level in patients with T2DM associated with MetS. Sixty patients who were diagnosed for the first time as T2DM associated with MetS were analyzed for insulin sensitivity, lipid profile, serum adiponectin and systemic inflammation. Those patients were randomly assigned to oral pioglitazone group (n = 30) or voglibose group (n = 30) in addition to conventional diet and exercise training. Body mass index and waist circumference did not change in the pioglitazone group, whereas these physical parameters significantly decreased in the voglibose group during a 6-month follow-up period. However, glycosylated hemoglobin, fasting plasma glucose, and HOMA-IR more significantly decreased in the pioglitazone group. The level of serum adiponectin especially high-molecular weight adiponectin markedly increased in the pioglitazone group. Moreover, high sensitive CRP significantly decreased only in the pioglitazone group. These results suggest that voglibose is superior in improving obesity, while pioglitazone is superior in ameliorating insulin sensitivity and increasing serum adiponectin in patients with an early stage of T2DM associated with MetS.

  8. Effect of the Interaction between Recanalization and Collateral Circulation on Functional Outcome in Acute Ischaemic Stroke.

    Science.gov (United States)

    Mangiafico, Salvatore; Saia, Valentina; Nencini, Patrizia; Romani, Ilaria; Palumbo, Vanessa; Pracucci, Giovanni; Consoli, Arturo; Rosi, Andrea; Renieri, Leonardo; Nappini, Sergio; Limbucci, Nicola; Inzitari, Domenico; Gensini, Gian Franco

    2014-12-01

    Identification of patients with acute ischaemic stroke who could most benefit from arterial recanalization after endovascular treatment remains an unsettled issue. Although several classifications of collateral circulation have been proposed, the clinical role of collaterals is still debated. We evaluated the effect of the collateral circulation in relation to recanalization as a predictor of clinical outcome. Data were prospectively collected from 103 patients consecutively treated for proximal middle cerebral or internal carotid artery occlusion. The collateral circulation was evaluated with a novel semiquantitative-qualitative score, the Careggi collateral score (CCS), in six grades. Both CCS and recanalization grades (TICI) were analysed in relation to clinical outcome. A statistical analysis was performed to evaluate the effect of interaction between recanalization and collateral circulation on clinical outcome. Out of the 103 patients, 37 (36.3%) had poor collaterals, and 65 (63.7%) had good collaterals. Patients with good collaterals had lower basal National Institute of Health Stroke Scale (NIHSS), more distal occlusion, smaller lesions at 24h CT scan and better functional outcome. After multivariate analysis, the interaction between recanalization and collateral grades was significantly stronger as a predictor of good outcome (OR 6.87, 95% CI 2.11-22.31) or death (OR 4.66, 95%CI 1.48-14.73) compared to the effect of the single variables. Collaterals showed an effect of interaction with the recanalization grade in determining a favourable clinical outcome. Assessment of the collateral circulation might help predict clinical results after recanalization in patients undergoing endovascular treatment for acute ischaemic stroke.

  9. Infarction Distribution Pattern in Acute Stroke May Predict the Extent of Leptomeningeal Collaterals

    Science.gov (United States)

    Verma, Rajeev Kumar; Gralla, Jan; Klinger-Gratz, Pascal Pedro; Schankath, Adrian; Jung, Simon; Mordasini, Pasquale; Zubler, Christoph; Arnold, Marcel; Buehlmann, Monika; Lang, Matthias F.

    2015-01-01

    Objective The aim of this study was to evaluate whether the distribution pattern of early ischemic changes in the initial MRI allows a practical method for estimating leptomeningeal collateralization in acute ischemic stroke (AIS). Methods Seventy-four patients with AIS underwent MRI followed by conventional angiogram and mechanical thrombectomy. Diffusion restriction in Diffusion weighted imaging (DWI) and correlated T2-hyperintensity of the infarct were retrospectively analyzed and subdivided in accordance with Alberta Stroke Program Early CT score (ASPECTS). Patients were angiographically graded in collateralization groups according to the method of Higashida, and dichotomized in 2 groups: 29 subjects with collateralization grade 3 or 4 (well-collateralized group) and 45 subjects with grade 1 or 2 (poorly-collateralized group). Individual ASPECTS areas were compared among the groups. Results Means for overall DWI-ASPECTS were 6.34 vs. 4.51 (well vs. poorly collateralized groups respectively), and for T2-ASPECTS 9.34 vs 8.96. A significant difference between groups was found for DWI-ASPECTS (p<0.001), but not for T2-ASPECTS (p = 0.088). Regarding the individual areas, only insula, M1-M4 and M6 showed significantly fewer infarctions in the well-collateralized group (p-values <0.001 to 0.015). 89% of patients in the well-collateralized group showed 0–2 infarctions in these six areas (44.8% with 0 infarctions), while 59.9% patients of the poor-collateralized group showed 3–6 infarctions. Conclusion Patients with poor leptomeningeal collateralization show more infarcts on the initial MRI, particularly in the ASPECTS areas M1 to M4, M6 and insula. Therefore DWI abnormalities in these areas may be a surrogate marker for poor leptomeningeal collaterals and may be useful for estimation of the collateral status in routine clinical evaluation. PMID:26327519

  10. Infarction Distribution Pattern in Acute Stroke May Predict the Extent of Leptomeningeal Collaterals.

    Directory of Open Access Journals (Sweden)

    Rajeev Kumar Verma

    Full Text Available The aim of this study was to evaluate whether the distribution pattern of early ischemic changes in the initial MRI allows a practical method for estimating leptomeningeal collateralization in acute ischemic stroke (AIS.Seventy-four patients with AIS underwent MRI followed by conventional angiogram and mechanical thrombectomy. Diffusion restriction in Diffusion weighted imaging (DWI and correlated T2-hyperintensity of the infarct were retrospectively analyzed and subdivided in accordance with Alberta Stroke Program Early CT score (ASPECTS. Patients were angiographically graded in collateralization groups according to the method of Higashida, and dichotomized in 2 groups: 29 subjects with collateralization grade 3 or 4 (well-collateralized group and 45 subjects with grade 1 or 2 (poorly-collateralized group. Individual ASPECTS areas were compared among the groups.Means for overall DWI-ASPECTS were 6.34 vs. 4.51 (well vs. poorly collateralized groups respectively, and for T2-ASPECTS 9.34 vs 8.96. A significant difference between groups was found for DWI-ASPECTS (p<0.001, but not for T2-ASPECTS (p = 0.088. Regarding the individual areas, only insula, M1-M4 and M6 showed significantly fewer infarctions in the well-collateralized group (p-values <0.001 to 0.015. 89% of patients in the well-collateralized group showed 0-2 infarctions in these six areas (44.8% with 0 infarctions, while 59.9% patients of the poor-collateralized group showed 3-6 infarctions.Patients with poor leptomeningeal collateralization show more infarcts on the initial MRI, particularly in the ASPECTS areas M1 to M4, M6 and insula. Therefore DWI abnormalities in these areas may be a surrogate marker for poor leptomeningeal collaterals and may be useful for estimation of the collateral status in routine clinical evaluation.

  11. M-type potassium channels modulate Schaffer collateral-CA1 glutamatergic synaptic transmission.

    Science.gov (United States)

    Sun, Jianli; Kapur, Jaideep

    2012-08-15

    Previous studies have suggested that muscarinic receptor activation modulates glutamatergic transmission. M-type potassium channels mediate the effects of muscarinic activation in the hippocampus, and it has been proposed that they modulate glutamatergic synaptic transmission. We tested whether M1 muscarinic receptor activation enhances glutamatergic synaptic transmission via the inhibition of the M-type potassium channels that are present in Schaffer collateral axons and terminals. Miniature excitatory postsynaptic currents (mEPSCs) were recorded from CA1 pyramidal neurons. The M1 receptor agonist, NcN-A-343, increased the frequency of mEPSCs, but did not alter their amplitude. The M-channel blocker XE991 and its analogue linopirdine also increased the frequency of mEPSCs. Flupirtine, which opens M-channels, had the opposite effect. XE991 did not enhance mEPSCs frequency in a calcium-free external medium. Blocking P/Q- and N-type calcium channels abolished the effect of XE991 on mEPSCs. These data suggested that the inhibition of M-channels increases presynaptic calcium-dependent glutamate release in CA1 pyramidal neurons. The effects of these agents on the membrane potentials of presynaptic CA3 pyramidal neurons were studied using current clamp recordings; activation of M1 receptors and blocking M-channels depolarized neurons and increased burst firing. The input resistance of CA3 neurons was increased by the application of McN-A-343 and XE991; these effects were consistent with the closure of M-channels. Muscarinic activation inhibits M-channels in CA3 pyramidal neurons and its efferents – Schaffer collateral, which causes the depolarization, activates voltage-gated calcium channels, and ultimately elevates the intracellular calcium concentration to increase the release of glutamate on CA1 pyramidal neurons.

  12. Effect of pioglitazone on arterial baroreflex sensitivity and sympathetic nerve activity in patients with acute myocardial infarction and type 2 diabetes mellitus.

    Science.gov (United States)

    Yokoe, Hiroshi; Yuasa, Fumio; Yuyama, Reisuke; Murakawa, Kousuke; Miyasaka, Yoko; Yoshida, Susumu; Tsujimoto, Satoshi; Sugiura, Tetsuro; Iwasaka, Toshiji

    2012-06-01

    Pioglitazone has been shown to reduce the occurrence of fatal and nonfatal myocardial infarction (MI) in type 2 diabetes mellitus (DM). However, the mechanisms of such favorable effects remain speculative. The aim of this study was to investigate the effect of pioglitazone on arterial baroreflex sensitivity (BRS) and muscle sympathetic nerve activity (MSNA) in 30 DM patients with recent MI. Patients were randomly assigned to those taking pioglitazone (n = 15) and those not taking pioglitazone (n = 15) at 4 weeks after the onset of MI. BRS, MSNA, calculated homeostasis model assessment of insulin resistance index (HOMA-IR), and plasma adiponectin were measured at baseline and after 12 weeks. Pioglitazone increased plasma adiponectin (from 6.9 ± 3.3 μg/dL to 12.2 ± 7.1 μg/dL) and reduced HOMA-IR (from 4.0 ± 2.2 to 2.1 ± 0.9). In the pioglitazone group, MSNA decreased significantly (from 37 ± 7 bursts/min to 25 ± 8 bursts/min) and BRS increased significantly (from 6.7 ± 3.0 to 9.9 ± 3.2 ms/mm Hg) after 12 weeks. Furthermore, a significant relationship was found between the change in MSNA and HOMA-IR (r = 0.6, P = 0.042). Thus, pioglitazone decreased the sympathetic nerve traffic through the improvement of insulin resistance in DM patients with recent MI, which indicate that the sympathoinhibitory effects of pioglitazone may, at least in part, have contributed to the beneficial effects of pioglitazone.

  13. Metabolic and other effects of pioglitazone as an add-on therapy to metformin in the treatment of polycystic ovary syndrome (PCOS).

    Science.gov (United States)

    Valsamakis, Georgios; Lois, Kostas; Kumar, Sudhesh; Mastorakos, George

    2013-01-01

    Insulin resistance is a key pathogenic defect of the clustered metabolic disturbances seen in polycystic ovary syndrome (PCOS). Metformin is an insulin sensitizer acting in the liver and the peripheral tissues that ameliorates the metabolic and reproductive defects in PCOS. In addition, pioglitazone is an insulin sensitizer used in diabetes mellitus type 2 (T2DM), improving insulin resistance (IR) in adipose tissue and muscles. In T2DM, these drugs are also used as a combined treatment due to their "add-on effect" on insulin resistance. Although the beneficial role of troglitazone (a member of the thiazolidinediones (TZDs) family) in PCOS has been shown in the past, currently only pioglitazone is available in the market. A few small randomized controlled trials have directly compared the effectiveness of pioglitazone in women with PCOS, while there are a limited number of small studies that support the beneficial metabolic add-on effect of pioglitazone on metformin-treated PCOS women as compared to metformin or pioglitazone monotherapy. These findings suggest a potentially promising role for combined pioglitazone/metformin treatment in the management of PCOS in metformin-resistant patients. In view of recent concerns regarding pioglitazone usage and its associated health risk, we aim to compare the pros and cons of each drug regarding their metabolic and other hormonal effects in women with PCOS and to explore the possible beneficial effect of combined therapy in certain cases, taking into consideration the teratogenic effect of pioglitazone. Finally, we discuss the need for a randomized controlled trial that will evaluate the metabolic and other hormonal effects of combined metformin/pioglitazone treatment in PCOS with selective treatment targets.

  14. Effect of pioglitazone on outcome following curative treatment for hepatocellular carcinoma in patients with hepatitis C virus infection: A prospective study.

    Science.gov (United States)

    Sumie, Shuji; Kawaguchi, Takumi; Kawaguchi, Atsushi; Kuromatsu, Ryoko; Nakano, Masahito; Satani, Manabu; Yamada, Shingo; Okamura, Shusuke; Yonezawa, Yuko; Kakuma, Tatsuyuki; Torimura, Takuji; Sata, Michio

    2015-01-01

    Pioglitazone is an insulin sensitizer used for the treatment of diabetes mellitus (DM). DM with insulin resistance is a risk factor for hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) infection. We aimed to investigate the effects of pioglitazone on HCC recurrence following treatment in HCV-infected patients. Between 2009 and 2011, 85 HCV-infected HCC patients who underwent curative treatment were enrolled in this prospective study. Among 45 patients with type 2 DM, 27 were administered pioglitazone (pioglitazone group) following treatment. The remaining 58 patients were assigned to the control group. The primary outcome was recurrence-free survival. Changes in insulin resistance and serum adiponectin levels resulting from pioglitazone treatment were also assessed. In the whole analysis (n=85), no significant difference in recurrence-free survival was observed between the pioglitazone and control groups. However, in a spline model analysis of DM patients, a decreased risk of HCC recurrence was associated with increased body weight in patients with a body mass index (BMI) ≥23; this association became significant at BMI ≥24 (hazard ratio=0.17; 95% confidence interval: 0.03-0.95). In addition, significantly decreased homeostasis model assessment for insulin resistance values (P=0.002) and significantly increased serum high-molecular-weight adiponectin levels (Ppioglitazone treatment. Although pioglitazone did not suppress HCC recurrence in the whole analysis, it inhibited HCC recurrence in overweight HCV-infected diabetic patients. Moreover, pioglitazone improved insulin resistance and adipocytokine levels. Thus, pioglitazone may suppress HCC recurrence, which is associated with glucose and fat metabolism disorders.

  15. In vitro-in vivo evaluation of fast-dissolving tablets containing solid dispersion of pioglitazone hydrochloride

    Directory of Open Access Journals (Sweden)

    Vinay Pandit

    2012-01-01

    Full Text Available Investigation of in vitro/in vivo behavior of fast-dissolving tablets containing solid dispersions of pioglitazone hydrochloride (PIO is the focus of the present research work. The effect of various hydrophilic polymers on the aqueous solubility of PIO was studied. Poly vinyl pyrrolidine K 30 (PVPK 30 carrier was selected and solid dispersions were prepared by various methods. Evaluation of solid dispersion for percentage yield, drug content, solubility, and Fourier Transform Infrared-indicated kneading method was most appropriate. Furthermore, the dissolution studies exhibited an enhancement in drug dissolution. One-way ANOVA of in vitro data suggested that there was significant (P ≤ 0.05 difference in dissolution profile of PIO solid dispersion when compared with pure drug and commercial product. Infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction performed on solid dispersion indicated lack of physicochemical interaction between the drug and the carrier. The selected formulation is compressed into fast-dissolving tablets which were further evaluated for tablet properties and in vitro drug release. In vivo studies of pure drug, selected formulation, and marketed product were carried out in male Wistar rats and pharmacokinetic parameters were calculated using Kinetica software 2000. The best formulation has shown T max of 1 hour which was highly significant (P < 0.01 when compared with pure drug and marketed formulation. Therefore, the solid dispersions prepared by kneading method using PVPK 30 as hydrophilic carrier can be successfully used for improvement of dissolution of PIO and resulted in faster onset of action as indicated by in vivo studies.

  16. The Effectiveness of Liraglutide in Nonalcoholic Fatty Liver Disease Patients with Type 2 Diabetes Mellitus Compared to Sitagliptin and Pioglitazone

    Directory of Open Access Journals (Sweden)

    Takamasa Ohki

    2012-01-01

    Full Text Available Background. Liraglutide leading to improve not only glycaemic control but also liver inflammation in non-alcoholic fatty liver disease (NAFLD patients. Aims. The aim of this study is to elucidate the effectiveness of liraglutide in NAFLD patients with type 2 diabetes mellitus (T2DM compared to sitagliptin and pioglitazone. Methods. We retrospectively enrolled 82 Japanese NAFLD patients with T2DM and divided into three groups (liraglutide: N = 26, sitagliptin; N = 36, pioglitazone; N = 20. We compared the baseline characteristics, changes of laboratory data and body weight. Results. At the end of follow-up, ALT, fast blood glucose, and HbA1c level significantly improved among the three groups. AST to platelet ratio significantly decreased in liraglutide group and pioglitazone group. The body weight significantly decreased in liraglutide group (81.8 kg to 78.0 kg, <0.01. On the other hands, the body weight significantly increased in pioglitazone group and did not change in sitagliptin group. Multivariate regression analysis indicated that administration of liraglutide as an independent factor of body weight reduction for more than 5% (OR 9.04; 95% CI 1.12–73.1, =0.04. Conclusions. Administration of liraglutide improved T2DM but also improvement of liver inflammation, alteration of liver fibrosis, and reduction of body weight.

  17. Improvement of cardiovascular risk markers by pioglitazone is independent from glycemic control - Results from the pioneer study

    NARCIS (Netherlands)

    Pfutzner, A; Marx, N; Lubben, G; Langenfeld, M; Walcher, D; Konrad, T; Forst, T

    2005-01-01

    OBJECTIVES This study was performed to assess whether the anti-inflammatory and antiatherogenic effects of pioglitazone suggested by animal experiments are reproducible in man and independent from improvements in metabolic control. BACKGROUND Type 2 diabetes is associated with increased cardiovascul

  18. Different effects of thiazolidinediones on cardiovascular risk in patients with type 2 diabetes mellitus: pioglitazone versus rosiglitazone.

    Science.gov (United States)

    Simó, R; Rodriguez, A; Caveda, E

    2010-07-02

    Cardiovascular disease remains the primary cause of mortality for patients with type 2 diabetes, which is characterized by insulin resistance. The thiazolidinediones (TZDs), also known as glitazones, are one of the pharmacological approaches to improve insulin sensitivity. At present, there are two available TZDs: pioglitazone and rosiglitazone. The common target of action for TZDs is the nuclear peroxisome proliferator-activated receptor-gamma (PPAR-gamma) that regulates the gene transcription involved in adipocyte differentiation and glucose and lipid metabolism. TZDs have shown similar effects on glycemic control, as well as on weight gain, fluid retention, increased risk of heart failure, and leg and forearm fractures. However, TZDs have differential effects on cardiovascular disease. This article will review the differential effects of pioglitazone and rosiglitazone on cardiovascular risk factors and outcomes, as well as the potential differences between them. Based upon available evidence, pioglitazone has a beneficial effect on cardiovascular disease. By contrast, it seems that rosiglitazone increases cardiovascular risk. The difference in lipid profile may be the main factor accounting for the superiority of pioglitazone in reducing cardiovascular risk.

  19. The effectiveness of liraglutide in nonalcoholic fatty liver disease patients with type 2 diabetes mellitus compared to sitagliptin and pioglitazone.

    Science.gov (United States)

    Ohki, Takamasa; Isogawa, Akihiro; Iwamoto, Masahiko; Ohsugi, Mitsuru; Yoshida, Haruhiko; Toda, Nobuo; Tagawa, Kazumi; Omata, Masao; Koike, Kazuhiko

    2012-01-01

    BACKGROUND. Liraglutide leading to improve not only glycaemic control but also liver inflammation in non-alcoholic fatty liver disease (NAFLD) patients. AIMS. The aim of this study is to elucidate the effectiveness of liraglutide in NAFLD patients with type 2 diabetes mellitus (T2DM) compared to sitagliptin and pioglitazone. METHODS. We retrospectively enrolled 82 Japanese NAFLD patients with T2DM and divided into three groups (liraglutide: N = 26, sitagliptin; N = 36, pioglitazone; N = 20). We compared the baseline characteristics, changes of laboratory data and body weight. RESULTS. At the end of follow-up, ALT, fast blood glucose, and HbA1c level significantly improved among the three groups. AST to platelet ratio significantly decreased in liraglutide group and pioglitazone group. The body weight significantly decreased in liraglutide group (81.8 kg to 78.0 kg, P pioglitazone group and did not change in sitagliptin group. Multivariate regression analysis indicated that administration of liraglutide as an independent factor of body weight reduction for more than 5% (OR 9.04; 95% CI 1.12-73.1, P = 0.04). CONCLUSIONS. Administration of liraglutide improved T2DM but also improvement of liver inflammation, alteration of liver fibrosis, and reduction of body weight.

  20. Protective effects of fish oil and pioglitazone on pancreatic tissue in obese KK mice with type 2 diabetes.

    Science.gov (United States)

    Iizuka, Yuzuru; Kim, Hyounju; Izawa, Takuya; Sakurai, Koji; Hirako, Satoshi; Wada, Masahiro; Matsumoto, Akiyo

    2016-12-01

    n-3 Polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have protective effects against the pancreatic β-cell dysfunction through several mechanisms. Thiazolidines are insulin sensitizers and are used in treating patients with type 2 diabetes. Our previous study demonstrated that a combination of fish oil, which is rich with EPA and DHA, and pioglitazone exerts beneficial effects on obesity and diabetes through their actions on the liver and adipose tissue. However, it remains largely unknown whether such combination therapy affects the pancreas. To answer this question, KK mice, which serve as a model for obesity and type 2 diabetes, were treated for 8 weeks with fish oil and pioglitazone. The combined regimen suppressed pancreatic islet hypertrophy (mean islet area decreased by an average of 49% vs. control) compared with mice treated with fish oil or pioglitazone alone (decreased by an average of 21% and 32% vs. control, respectively). Compared with the controls, individual or combined treatment significantly increased the percentage of β-cell area in the pancreatic islets, significantly decreased endoplasmic reticulum stress, and reduced the percentage of apoptotic cell death in the pancreatic islets. These findings suggest that fish oil and/or pioglitazone prevents β-cell dysfunction by improving the insulin resistance and decreasing the ER stress.

  1. Revitalization of pioglitazone: the optimum agent to be combined with a sodium-glucose co-transporter-2 inhibitor.

    Science.gov (United States)

    DeFronzo, R A; Chilton, R; Norton, L; Clarke, G; Ryder, R E J; Abdul-Ghani, M

    2016-05-01

    The recently completed EMPA-REG study showed that empagliflozin significantly decreased the major adverse cardiac events (MACE) endpoint, which comprised cardiovascular death, non-fatal myocardial infarction (MI) and stroke, in patients with high-risk type 2 diabetes (T2DM), primarily through a reduction in cardiovascular death, without a significant decrease in either MI or stroke. In the PROactive study, pioglitazone decreased the MACE endpoint by a similar degree to that observed in the EMPA-REG study, through a marked reduction in both recurrent MI and stroke and a modest reduction in cardiovascular death. These observations suggest that pioglitazone might be an ideal agent to combine with empagliflozin to further reduce cardiovascular events in patients with high-risk diabetes as empagliflozin also promotes salt/water loss and would be expected to offset any fluid retention associated with pioglitazone therapy. In the present paper, we provide an overview of the potential benefits of combined pioglitazone/empagliflozin therapy to prevent cardiovascular events in patients with T2DM.

  2. DEVELOPMENT AND EVALUATION OF MICROBALLOONS OF PIOGLITAZONE HYDROCHLORIDE USING EUDRAGIT S-100

    Directory of Open Access Journals (Sweden)

    Nishant S. Gandhi et al.

    2012-01-01

    Full Text Available ABSTRACTKeywords:Pioglitazone hydrochloride,Eudragit S-100,Solvent diffusion evaporation,Floating microspheres,Polymer: Drug ratioCorrespondence to Author:Nishant GandhiOld Power House Road, Ramnagar, Gondia, Maharashtra, IndiaVarious approaches have been used to retain the dosage form in the stomach as a way of increasing the gastric residence time (GRT, including floatation systems; high-density systems; mucoadhesive systems; magnetic systems; unfoldable, extendible, or swellable systems; and superporous hydrogel systems. The aim of this study was to prepare and evaluate floating microspheres of Pioglitazone hydrochloride for the prolongation of gastric residence time. The microspheres were prepared by emulsion solvent diffusion-evaporation method using Eudragit S-100. A full factorial design was applied to optimize the formulation. Preliminary studies revealed that the concentration of polymer and stirring speed significantly affected the characteristics of floating microspheres. The optimum batch of microspheres exhibited some rough surfaces with good flow and packing properties, prolonged sustained drug release, remained buoyant for more than 10 hrs, high entrapment efficiency upto 89%w/w. Scanning electron microscopy confirmed the hollow structure with particle size in the order of 270 µm. The studies revealed that decrease in particle size of the microspheres increase the drug release from the floating microspheres. The results of 32 full factorial design revealed that the Polymer: Drug (P: D ratio (X1 and stirring speed (X2 significantly affected drug entrapment efficiency, percentage release after 8 h and particle size of microspheres.

  3. Development and optimization of novel controlled-release pioglitazone provesicular powders using 3² factorial design.

    Science.gov (United States)

    Shukr, Marwa H; Eltablawy, Nadia A

    2015-02-01

    This work aimed at studying a novel controlled drug delivery proniosomal formulation of pioglitazone for treatment of diabetes type-2. The effects of independent variables like type of surfactant and ratio of surfactants/cholesterol were studied using 3(2) factorial design. The provesicular powders were characterized regarding their encapsulation efficiency, vesicle size, morphology, and in vitro drug release. The revealed optimal provesicular powder was exposed to stability testing and in vivo performance evaluation. Results showed that F6 was selected as the optimal formulation, and its in vivo hypoglycemic effect on normal healthy and STZ-induced diabetic albino rats was investigated. F6 proniosomal formulation exhibited a significantly higher % decrease (56.18 % for STZ-induced diabetic albino rats) of blood glucose level (BGL) than Actos® (32. % for STZ-induced diabetic albino rats). Higher % decrease of BGL with longer t max and lower AUC0-24 confirms the development of a successful proniosomal pioglitazone formulation.

  4. Liquid Chromatographic Determination of Pioglitazone in Pharmaceuticals, Serum and Urine Samples

    Directory of Open Access Journals (Sweden)

    Shahnaz Perveen

    2011-12-01

    Full Text Available A rapid and reliable analytical method based on high-performance liquid chromatography (HPLC with UV detection (221nm has been developed for the determination of the anti-hyperglycemic agent Pioglitazone in pharmaceutical formulations and biological fluids (serum and urine after clean-up with solid-phase extraction. Chromatographic separation was achieved with a Chromolith® Performance RP-18e (100×4.6mm column using mobile phase composition of acetonitrile: mixed phosphate buffer (pH 2.5; 10mM (30:70, v/v with a flow rate of 2.0mL/min. The total run time was 2 min. under optimized conditions. The calibration curve was found to be linear in the range of 1-10 µg mL-1 with regression coefficient of 0.9996, and the lower limit of detection 72 ng/20µL injection. The method has been validated for the system suitability, linearity, precision and accuracy, limits of detection, specificity, stability and robustness. The %recovery of Pioglitazone in pharmaceutical formulations was found to be 104.7%. The assay has been applied successfully to the pharmaceutical Tablet samples and biological fluids (serum and urine of healthy volunteers.

  5. Regulation of Diet-Induced Adipose Tissue and Systemic Inflammation by Salicylates and Pioglitazone

    Science.gov (United States)

    Kamei, Nozomu; Shimada, Takeshi; Liu, Libin; Moore, Kristin; Woo, Ju Rang; Shoelson, Steven E.; Lee, Jongsoon

    2013-01-01

    It is increasingly accepted that chronic inflammation participates in obesity-induced insulin resistance and type 2 diabetes (T2D). Salicylates and thiazolidinediones (TZDs) both have anti-inflammatory and anti-hyperglycemic properties. The present study compared the effects of these drugs on obesity-induced inflammation in adipose tissue (AT) and AT macrophages (ATMs), as well as the metabolic and immunological phenotypes of the animal models. Both drugs improved high fat diet (HFD)-induced insulin resistance. However, salicylates did not affect AT and ATM inflammation, whereas Pioglitazone improved these parameters. Interestingly, HFD and the drug treatments all modulated systemic inflammation as assessed by changes in circulating immune cell numbers and activation states. HFD increased the numbers of circulating white blood cells, neutrophils, and a pro-inflammatory monocyte subpopulation (Ly6Chi), whereas salicylates and Pioglitazone normalized these cell numbers. The drug treatments also decreased circulating lymphocyte numbers. These data suggest that obesity induces systemic inflammation by regulating circulating immune cell phenotypes and that anti-diabetic interventions suppress systemic inflammation by normalizing circulating immune phenotypes. PMID:24376593

  6. Pioglitazone--do we really need it to manage type 2 diabetes?

    Science.gov (United States)

    Sinha, Binayak; Ghosal, Samit

    2013-01-01

    Over the last few years a number of important drugs like rofecoxib, rosiglitazone, gatifloxacin (in diabetics) have lost their position in disease management. The newest controversy revolves around Pioglitazone, a thiozolidindione, which improves insulin sensitivity and is reputed to have cardioprotective actions, but is riddled with several controversies related to weight gain, distal fractures of long bones, recent reports of bladder cancer and others. There are now new groups of drugs, which have been introduced with stringent FDA approval. These include DPP-4 inhibitors, GLP-1 analogues and bromocriptine (old wine in a new bottle). Early in 2013 we are also looking at the launch of another new agent - SGLT-2 inhibitors. These newer agents are associated with not only a significant glucose lowering effect but also positive extra-glycaemic benefits principally in the areas of hypoglycaemia and weight gain. This raises a very important question - do we really need such a controversial agent when such a plethora of agents are available to us with possibly better metabolic profile than pioglitazone? This review addresses this highly contentious area dissecting the pros and cons as we see it.

  7. Alogliptin in combination with metformin and pioglitazone for the treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Holland, Daniel Q; Neumiller, Joshua J

    2014-01-01

    Alogliptin is a selective dipeptidyl peptidase-4 inhibitor recently marketed for once-daily administration in the treatment of type 2 diabetes mellitus (T2DM). Fixed-dose combinations of alogliptin with both metformin and pioglitazone are also commercially available, providing a measure of convenience in addition to an effective mode of delivering combination therapy to improve glycemic control. Alogliptin has been studied clinically as initial therapy in treatment-naïve patients with T2DM and as initial therapy or add-on in combination with other antidiabetic agents. Clinical trial data with alogliptin demonstrate clinical efficacy in terms of glycosylated hemoglobin A1c and fasting plasma glucose reductions when used both as monotherapy and as a component of two- or three-drug combination regimens for the treatment of T2DM. Extensive Phase II and Phase III clinical trial data support the use of alogliptin in combination with metformin and pioglitazone. Glycemic reduction with both combinations is similar to the sum of the respective monotherapies, with adverse event rates similar - or more moderate - than those observed with up-titration of monotherapy or the addition of other antihyperglycemic agents.

  8. A Validated Adsorptive Stripping Voltammetric Determination of Antidiabetic Agent Pioglitazone HCl in Tablets and Biological Fluids

    Science.gov (United States)

    Al-Arfaj, Nawal Ahmad; Al-Abdulkareem, Eman Abdullah; Aly, Fatma Ahmad

    2008-01-01

    Square-wave adsorptive cathodic stripping voltammetry was used to determine pioglitazone HCl in Britton Robinson buffer of pH5. The adsorptive cathodic peak was observed at -1.5 V vs. Ag/AgCl. The peak response was characterized with respect to pH, supporting electrolyte, frequency, scan increment, pulse-amplitude, accumulation potential and pre-concentration time. Under optimal conditions, the peak current is proportional to the concentration of pioglitazone HCl, and a linear calibration graphs were obtained within the concentration levels of 10-8 and 10-4 M following different accumulation time periods (0-300 s). The obtained results were analyzed and the statistical parameters were calculated. The detection limit is 8.08 × 10-9 M (3.17 ng ml-1) using 300 s pre-concentration time, whereas the quantitative limit is 2.45 × 10-8 M (9.63 ng ml-1). The proposed method was applied to assay the drug in pharmaceutical formulations and biological fluids. The pharmacokinetic parameters of drug in human plasma were estimated as: Cmax=785.8 ng ml-1, tmax=1.5 h, Ke=0.125 h-1 and t1/2=8 h which are favorably compared with those reported in literature. PMID:23675103

  9. Plasma Catestatin: A Useful Biomarker for Coronary Collateral Development with Chronic Myocardial Ischemia

    Science.gov (United States)

    Xu, Weixian; Yu, Haiyi; Li, Weihong; Gao, Wei; Guo, Lijun; Wang, Guisong

    2016-01-01

    Backgrounds Catestatin is an endogenous multifunctional neuroendocrinepeptide. Recently, catestatin was discovered as a novel angiogenic cytokine. The study was to investigate the associations between endogenous catestatin and coronary collateral development among the patients with chronic myocardial ischemia. Methods Thirty-eight patients with coronary artery chronic total occlusions (CTO) (CTO group) and 38 patients with normal coronary arteries (normal group) were enrolled in the series. Among the patients with CTO, coronary collateral development was graded according to the Rentrop score method. Rentrop score 0–1 collateral development was regarded as poor collateral group and 2–3 collateral development was regarded as good collateral group. Plasma catestatin level and vascular endothelial growth factor (VEGF) were measured by ELISA kits. Results The plasma catestatin levels in CTO group were significantly higher than that in normal group (1.97±1.01 vs 1.36±0.97ng/ml, p = 0.009). In the CTO group, the patients with good collateral development had significantly higher catestatin and VEGF levels than those with poor collateral development (2.36±0.73 vs 1.61±1.12 ng/ml, p = 0.018; 425.23±140.10 vs 238.48±101.00pg/mL, pCTO. However, there is no correlations between plasma catestatin levels and VEGF (r = -0.06, p = 0.744). In the multiple linear regression models, plasma catestatin level was one of the independent factors of coronary collateral development after adjustment for confounders. Conclusions Plasma catestatin was associated with coronary collateral developments. It may be a useful biomarker for coronary collateral development and potential target for therapeutic angiogenesis in patients with CTO. PMID:27304618

  10. Pioglitazone can ameliorate insulin resistance in low-dose streptozotocin and high sucrose-fat diet induced obese rats

    Institute of Scientific and Technical Information of China (English)

    Shi-ying DING; Zhu-fang SHEN; Yue-teng CHEN; Su-juan SUN; Quan Liu; Ming-zhi XIE

    2005-01-01

    Aim: To investigate the effect of the peroxisome proliferator-activator receptor (PPAR)-γ agonist, pioglitazone, on insulin resistance in low-dose streptozotocin and high sucrose-fat diet induced obese rats. Methods: Normal female Wistar rats were injected intraperitoneally with low-dose streptozotocin (STZ, 30 mg/kg) and fed with a high sucrose-fat diet for 8 weeks. Pioglitazone (20 mg/kg) was administered orally to the obese and insulin-resistant rats for 28 d. Intraperitoneal glucose tolerance tests, insulin tolerance tests and gluconeogenesis tests were carried out over the last 14 d. At the end of d 28 of the treatment, serums were collected for biochemical analysis. Glucose transporter 4 (GLUT4) and insulin receptor substrate-1 (IRS-1) protein expression in the liver and skeletal muscle were detected using Western blotting. Results: Significant insulin resistance and obesity were observed in low-dose STZ and high sucrose-fat diet induced obese rats. Pioglitazone (20 mg/kg) treatment significantly decreased serum insulin,triglyceride and free fatty acid levels, and elevated high density lipoprotein-cholesterol (HDL-C) levels. Pioglitazone also lowered the lipid contents in the liver and muscles of rats undergoing treatment. Gluconeogenesis was inhibited and insulin sensitivity was improved markedly. The IRS-1 protein contents in the liver and skeletal muscles and the GLUT4 contents in skeletal muscle were elevated significantly. Conclusion: The data suggest that treatment with pioglitazone improves insulin sensitivity in low-dose STZ and high sucrose-fat diet induced obese rats. The insulin sensitizing effect may be associated with ameliorating lipid metabolism, reducing hyperinsulinemia, inhibiting gluconeogenesis, and increasing IRS-1 and GLUT4 protein expression in insulin-sensitive tissues.

  11. The Peroxisome Proliferator Activated Receptor‐γ Pioglitazone Improves Vascular Function and Decreases Disease Activity in Patients With Rheumatoid Arthritis

    Science.gov (United States)

    Marder, Wendy; Khalatbari, Shokoufeh; Myles, James D.; Hench, Rita; Lustig, Susan; Yalavarthi, Srilakshmi; Parameswaran, Aishwarya; Brook, Robert D.; Kaplan, Mariana J.

    2013-01-01

    Background Rheumatoid arthritis (RA) is associated with heightened mortality due to atherosclerotic cardiovascular disease (CVD). Inflammatory pathways in RA negatively affect vascular physiology and promote metabolic disturbances that contribute to CVD. We hypothesized that the peroxisome proliferator activated receptor‐γ (PPAR‐γ) pioglitazone could promote potent vasculoprotective and anti‐inflammatory effects in RA. Methods and Results One hundred forty‐three non‐diabetic adult RA patients (76.2% female, age 55.2±12.1 [mean±SD]) on stable RA standard of care treatment were enrolled in a randomized, double‐blind placebo controlled crossover trial of 45 mg daily pioglitazone versus placebo, with a 3‐month duration/arm and a 2‐month washout period. Pulse wave velocity of the aorta (PWV), brachial artery flow mediated dilatation (FMD), nitroglycerin mediated dilatation (NMD), microvascular endothelial function (reactive hyperemia index [RHI]), and circulating biomarkers of inflammation, insulin resistance, and atherosclerosis risk all were quantified. RA disease activity was assessed with the 28‐Joint Count Disease Activity Score (DAS‐28) C‐reactive protein (CRP) and the Short Form (36) Health Survey quality of life questionnaire. When added to standard of care RA treatment, pioglitazone significantly decreased pulse wave velocity (ie, aortic stiffness) (P=0.01), while FMD and RHI remained unchanged when compared to treatment with placebo. Further, pioglitazone significantly reduced RA disease activity (P=0.02) and CRP levels (P=0.001), while improving lipid profiles. The drug was well tolerated. Conclusions Addition of pioglitazone to RA standard of care significantly improves aortic elasticity and decreases inflammation and disease activity with minimal safety issues. The clinical implications of these findings remain to be established. Clinical Trial Registration URL: ClinicalTrials.gov Unique Identifier: NCT00554853. PMID:24252844

  12. Pioglitazone, a PPARγ agonist rescues depression associated with obesity using chronic unpredictable mild stress model in experimental mice.

    Science.gov (United States)

    Kurhe, Yeshwant; Mahesh, Radhakrishnan

    2016-06-01

    Pioglitazone, a peroxisome proliferator activated receptor gamma (PPARγ) agonist belonging to thiazolidinedione class, is mainly used in diabetes mellitus. Obese subjects are twice likely to become depressed than non-obese individuals. The biological mechanisms linking depression with obesity still remain poorly understood and there is immense need for better therapeutic intervention against such co-morbid disorders. The present study investigates the effect of pioglitazone on the chronic unpredictable mild stress (CUMS) induced depression in obese mice by using behavioral tests and biochemical estimations. Mice were fed with high fat diet (HFD) for 14 weeks and were further subjected to different stress procedures for 28 days to induce depressive behavior. Animals were administered orally with pioglitazone (30 mg/kg p.o.)/escitalopram (10 mg/kg p.o.)/vehicle (10 ml/kg p.o.) daily from day 15-28. Various behavioral paradigms such as sucrose preference test, forced swim test (FST), tail suspension test (TST) and elevated plus maze (EPM) were performed. Biochemical estimations including plasma glucose, total cholesterol, triglycerides, and total proteins were performed. The data obtained from behavioral assays and biochemical assessments indicated that obese animals exhibited severe depressive-like behavior compared to non-obese animals. Furthermore, obese animals subjected to CUMS worsen the depressive behavior compared to obese control animals. Repetitive treatment with pioglitazone reversed the CUMS induced behavioral and biochemical alterations in HFD fed obese mice which atleast in part may be mediated through improving altered plasma glucose. The study suggests that pioglitazone needs further attention with respect to molecular mechanisms that could provide a better therapeutic strategy against depression associated with obesity.

  13. Pioglitazone, a PPARγ agonist rescues depression associated with obesity using chronic unpredictable mild stress model in experimental mice

    Directory of Open Access Journals (Sweden)

    Yeshwant Kurhe

    2016-06-01

    Full Text Available Pioglitazone, a peroxisome proliferator activated receptor gamma (PPARγ agonist belonging to thiazolidinedione class, is mainly used in diabetes mellitus. Obese subjects are twice likely to become depressed than non-obese individuals. The biological mechanisms linking depression with obesity still remain poorly understood and there is immense need for better therapeutic intervention against such co-morbid disorders. The present study investigates the effect of pioglitazone on the chronic unpredictable mild stress (CUMS induced depression in obese mice by using behavioral tests and biochemical estimations. Mice were fed with high fat diet (HFD for 14 weeks and were further subjected to different stress procedures for 28 days to induce depressive behavior. Animals were administered orally with pioglitazone (30 mg/kg p.o./escitalopram (10 mg/kg p.o./vehicle (10 ml/kg p.o. daily from day 15–28. Various behavioral paradigms such as sucrose preference test, forced swim test (FST, tail suspension test (TST and elevated plus maze (EPM were performed. Biochemical estimations including plasma glucose, total cholesterol, triglycerides, and total proteins were performed. The data obtained from behavioral assays and biochemical assessments indicated that obese animals exhibited severe depressive-like behavior compared to non-obese animals. Furthermore, obese animals subjected to CUMS worsen the depressive behavior compared to obese control animals. Repetitive treatment with pioglitazone reversed the CUMS induced behavioral and biochemical alterations in HFD fed obese mice which atleast in part may be mediated through improving altered plasma glucose. The study suggests that pioglitazone needs further attention with respect to molecular mechanisms that could provide a better therapeutic strategy against depression associated with obesity.

  14. Time-resolved assessment of collateral flow using 4D CT angiography in large-vessel occlusion stroke

    Energy Technology Data Exchange (ETDEWEB)

    Froelich, Andreas M.J.; Wolff, Sarah Lena; Psychogios, Marios N.; Schramm, Ramona; Knauth, Michael; Schramm, Peter [University Medical Centre Goettingen, Department of Neuroradiology, Goettingen (Germany); Klotz, Ernst [Computed Tomography H IM CR R and D PA, Siemens AG, Forchheim (Germany); Wasser, Katrin [University Medical Centre Goettingen, Department of Neurology, Goettingen (Germany)

    2014-02-15

    In acute stroke patients with large vessel occlusion, collateral blood flow affects tissue fate and patient outcome. The visibility of collaterals on computed tomography angiography (CTA) strongly depends on the acquisition phase, but the optimal time point for collateral imaging is unknown. We analysed collaterals in a time-resolved fashion using four-dimensional (4D) CTA in 82 endovascularly treated stroke patients, aiming to determine which acquisition phase best depicts collaterals and predicts outcome. Early, peak and late phases as well as temporally fused maximum intensity projections (tMIP) were graded using a semiquantitative regional leptomeningeal collateral score, compared with conventional single-phase CTA and correlated with functional outcome. The total extent of collateral flow was best visualised on tMIP. Collateral scores were significantly lower on early and peak phase as well as on single-phase CTA. Collateral grade was associated with favourable functional outcome and the strength of this relationship increased from earlier to later phases, with collaterals on tMIP showing the strongest correlation with outcome. Temporally fused tMIP images provide the best depiction of collateral flow. Our findings suggest that the total extent of collateral flow, rather than the velocity of collateral filling, best predicts clinical outcome. (orig.)

  15. Collateral methotrexate resistance in cisplatin-selected murine leukemia cells

    Directory of Open Access Journals (Sweden)

    Bhushan A.

    1999-01-01

    Full Text Available Resistance to anticancer drugs is a major cause of failure of many therapeutic protocols. A variety of mechanisms have been proposed to explain this phenomenon. The exact mechanism depends upon the drug of interest as well as the tumor type treated. While studying a cell line selected for its resistance to cisplatin we noted that the cells expressed a >25,000-fold collateral resistance to methotrexate. Given the magnitude of this resistance we elected to investigate this intriguing collateral resistance. From a series of investigations we have identified an alteration in a membrane protein of the resistant cell as compared to the sensitive cells that could be the primary mechanism of resistance. Our studies reviewed here indicate decreased tyrosine phosphorylation of a protein (molecular mass = 66 in the resistant cells, which results in little or no transfer of methotrexate from the medium into the cell. Since this is a relatively novel function for tyrosine phosphorylation, this information may provide insight into possible pharmacological approaches to modify therapeutic regimens by analyzing the status of this protein in tumor samples for a better survival of the cancer patients.

  16. Studies on linearty and assay using RP-HPLC and UV-visible spectroscopy for the drugs oxcarbazepine and pioglitazone before and after expiry period

    National Research Council Canada - National Science Library

    Suganya, S; Bright, A; Devi, T.S. Renuga

    2012-01-01

    .... In the present investigation RP-HPLC and UV-Visible spectroscopic methods are employed for estimation of drugs oxcarbazepine and pioglitazone in tablet dosage form before expiry period and 10-12 months after its expiry...

  17. HPLC method development, validation and its application to investigate in vitro effect of pioglitazone on the availability of H1 receptor antagonists

    Directory of Open Access Journals (Sweden)

    Agha Zeeshan Mirza

    2017-02-01

    Full Text Available The method has been developed and validated for the simultaneous determination of pioglitazone and H1-receptor antagonists (fexofenadine, cetirizine and levocetirizine in formulations and human serum. Utilizing HPLC techniques, an assay was designed to determine the in vitro effects of pioglitazone on H1-receptor antagonists. Obtained results were verified using the UV spectrophotometric technique. First-derivative values versus concentrations were used to plot calibration curves of these drugs and were found to similar with the HPLC data. The availability of pioglitazone remained unchanged in absence or presence of fexofenadine, cetirizine and levocetirizine. This in vitro analysis confirms the harmless co-administration of pioglitazone and H1-receptor antagonists, and can serve as the foundation for designing further in vivo studies.

  18. Laparoscopic umbilical hernia repair in the presence of extensive paraumbilical collateral veins: A case report

    NARCIS (Netherlands)

    S.S. Lases (Seilenna); H.H. Eker (Hasan); E.G.J.M. Pierik; P. Klitsie (Pieter); B. de Goede (Barry); M.P.F.V. Peeters; G. Kazemier (Geert); J.F. Lange (Johan)

    2011-01-01

    textabstractA patient with an umbilical hernia presenting with collateral veins in the abdominal wall and umbilicus is a case that every hernia surgeon has to deal with occasionally. Several underlying diseases have been described to provoke collateral veins in the abdominal wall. However, the treat

  19. Circulating MicroRNAs Characterizing Patients with Insufficient Coronary Collateral Artery Function

    NARCIS (Netherlands)

    Hakimzadeh, Nazanin; Nossent, A Yaël; van der Laan, Anja M; Schirmer, Stephan H; de Ronde, Maurice W J; Pinto-Sietsma, Sara-Joan; van Royen, Niels; Quax, Paul H A; Höfer, Imo E.|info:eu-repo/dai/nl/267105649; Piek, Jan J

    2015-01-01

    BACKGROUND: Coronary collateral arteries function as natural bypasses in the event of coronary obstruction. The degree of collateral network development significantly impacts the outcome of patients after an acute myocardial infarction (AMI). MicroRNAs (miRNAs, miRs) have arisen as biomarkers to ide

  20. Relationship between haemodynamic impairment and collateral blood flow in carotid artery disease

    DEFF Research Database (Denmark)

    Hartkamp, Nolan S; Petersen, Esben T; Chappell, Michael A

    2017-01-01

    is influenced at brain tissue level by the existence of primary and/or secondary collateral. Eighty-eight patients with steno-occlusive ICA disease and 29 healthy controls underwent MR examination. The presence of collaterals was determined with time-of-flight, two-dimensional phase contrast MRA and territorial...

  1. 13 CFR 123.11 - Does SBA require collateral for any of its disaster loans?

    Science.gov (United States)

    2010-01-01

    ... any of its disaster loans? 123.11 Section 123.11 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Overview § 123.11 Does SBA require collateral for any of its disaster loans? Generally, SBA will not require that you pledge collateral to secure a disaster home loan or a...

  2. Tests of Ex Ante Versus Ex Post Theories of Collateral Using Private and Public Information

    NARCIS (Netherlands)

    Berger, A.N.; Frame, W.S.; Ioannidou, V.

    2010-01-01

    Collateral is a widely used, but not well understood, debt contracting feature. Two broad strands of theoretical literature explain collateral as arising from the existence of either ex ante private information or ex post incentive problems between borrowers and lenders. However, the extant

  3. SmPL: A Domain-Specific Language for Specifying Collateral Evolutions in Linux Device Drivers

    DEFF Research Database (Denmark)

    Padioleau, Yoann; Lawall, Julia Laetitia; Muller, Gilles

    2007-01-01

    identifying the affected files and modifying all of the code fragments in these files that in some way depend on the changed interface. We have studied the collateral evolution problem in the context of Linux device drivers. Currently, collateral evolutions in Linux are mostly done manually using a text...

  4. 7 CFR 1980.443 - Collateral, personal and corporate guarantees and other requirements.

    Science.gov (United States)

    2010-01-01

    ... the percentage to be applied in the analysis are to be based on the realizable value of the accounts... receivable, cash or special cash collateral accounts, marketable securities and cash surrender value of life... the loan balance without adequate consideration for the value of that collateral....

  5. 46 CFR 308.522 - Collateral deposit fund, letter of transmittal, Form MA-302.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Collateral deposit fund, letter of transmittal, Form MA-302. 308.522 Section 308.522 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY... Collateral deposit fund, letter of transmittal, Form MA-302. The standard form of letter of transmittal...

  6. 76 FR 35141 - Protection of Cleared Swaps Customer Contracts and Collateral; Conforming Amendments to the...

    Science.gov (United States)

    2011-06-16

    ... corrects the formatting of text and charts published in the Federal Register of June 09, 2011 (76 FR 33818), regarding Protection of Cleared Swaps Customer Contracts and Collateral; Conforming Amendments to the... Collateral; Conforming Amendments to the Commodity Broker Bankruptcy Provisions; Correction AGENCY:...

  7. 7 CFR 1980.444 - Appraisal of property serving as collateral.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 14 2010-01-01 2009-01-01 true Appraisal of property serving as collateral. 1980.444 Section 1980.444 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING... Program § 1980.444 Appraisal of property serving as collateral. (a) Appraisal reports prepared...

  8. 10 CFR 611.108 - Perfection of liens and preservation of collateral.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Perfection of liens and preservation of collateral. 611.108 Section 611.108 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS ADVANCED TECHNOLOGY... determines are required to preserve the collateral. The cost of such contracts may be charged to the Borrower....

  9. Circulating MicroRNAs Characterizing Patients with Insufficient Coronary Collateral Artery Function

    NARCIS (Netherlands)

    Hakimzadeh, Nazanin; Nossent, A Yaël; van der Laan, Anja M; Schirmer, Stephan H; de Ronde, Maurice W J; Pinto-Sietsma, Sara-Joan; van Royen, Niels; Quax, Paul H A; Höfer, Imo E.; Piek, Jan J

    2015-01-01

    BACKGROUND: Coronary collateral arteries function as natural bypasses in the event of coronary obstruction. The degree of collateral network development significantly impacts the outcome of patients after an acute myocardial infarction (AMI). MicroRNAs (miRNAs, miRs) have arisen as biomarkers to ide

  10. 13 CFR 123.513 - Does SBA require collateral on its Military Reservist EIDL?

    Science.gov (United States)

    2010-01-01

    ... Military Reservist EIDL? 123.513 Section 123.513 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION DISASTER LOAN PROGRAM Military Reservist Economic Injury Disaster Loans § 123.513 Does SBA require collateral on its Military Reservist EIDL? SBA will not generally require you to pledge collateral to...

  11. Transcatheter embolization of extensive left gastric artery collaterals presenting with massive upper gastrointestinal bleed.

    Science.gov (United States)

    Saddekni, Souheil; Abdel-Aal, Ahmed Kamel; Oser, Rachel F; Underwood, Edgar; Bag, Asim

    2012-08-01

    We report a case of extensive left gastric artery collaterals that were formed in the region of gastric fundus due to splenic artery occlusion and resulted in massive hematemesis. These collaterals were thought to be portosystemic collaterals related to portal hypertension during upper endoscopy study and single-phase venous computed tomography studies. The collaterals were treated by transcatheter endovascular coil embolization. Our case highlights the importance of recognizing and differentiating left gastric artery collaterals from gastric venous varices as a cause of hematemesis since the treatment approach for each condition is totally different. It also introduces the feasibility of percutaneous left gastric artery embolization as a treatment for this condition, without the need for surgical splenectomy and partial gastrectomy which have a higher mortality and morbidity.

  12. Collateral blood vessels in acute ischemic stroke: a physiological window to predict future outcomes

    Directory of Open Access Journals (Sweden)

    Heitor Castelo Branco Rodrigues Alves

    2016-01-01

    Full Text Available ABSTRACT Collateral circulation is a physiologic pathway that protects the brain against ischemic injury and can potentially bypass the effect of a blocked artery, thereby influencing ischemic lesion size and growth. Several recent stroke trials have provided information about the role of collaterals in stroke pathophysiology, and collateral perfusion has been recognized to influence arterial recanalization, reperfusion, hemorrhagic transformation, and neurological outcomes after stroke. Our current aim is to summarize the anatomy and physiology of the collateral circulation and to present and discuss a comprehensible review of the related knowledge, particularly the effects of collateral circulation on the time course of ischemic injury and stroke severity, as well as imaging findings and therapeutic implications.

  13. De-novo collateral formation following acute myocardial infarction: Dependence on CCR2⁺ bone marrow cells.

    Science.gov (United States)

    Zhang, Hua; Faber, James E

    2015-10-01

    Wide variation exists in the extent (number and diameter) of native pre-existing collaterals in tissues of different strains of mice, with supportive indirect evidence recently appearing for humans. This variation is a major determinant of the wide variation in severity of tissue injury in occlusive vascular disease. Whether such genetic-dependent variation also exists in the heart is unknown because no model exists for study of mouse coronary collaterals. Also owing to methodological limitations, it is not known if ischemia can induce new coronary collaterals to form ("neo-collaterals") versus remodeling of pre-existing ones. The present study sought to develop a model to study coronary collaterals in mice, determine whether neo-collateral formation occurs, and investigate the responsible mechanisms. Four strains with known rank-ordered differences in collateral extent in brain and skeletal muscle were studied: C57BLKS>C57BL/6>A/J>BALB/c. Unexpectedly, these and 5 additional strains lacked native coronary collaterals. However after ligation, neo-collaterals formed rapidly within 1-to-2 days, reaching their maximum extent in ≤7 days. Rank-order for neo-collateral formation differed from the above: C57BL/6>BALB/c>C57BLKS>A/J. Collateral network conductance, infarct volume(-1), and contractile function followed this same rank-order. Neo-collateral formation and collateral conductance were reduced and infarct volume increased in MCP1(-/-) and CCR2(-/-) mice. Bone-marrow transplant rescued collateral formation in CCR2(-/-) mice. Involvement of fractalkine➔CX3CR1 signaling and endothelial cell proliferation were also identified. This study introduces a model for investigating the coronary collateral circulation in mice, demonstrates that neo-collaterals form rapidly after coronary occlusion, and finds that MCP➔CCR2-mediated recruitment of myeloid cells is required for this process.

  14. Pioglitazone improves reversal learning and exerts mixed cerebrovascular effects in a mouse model of Alzheimer's disease with combined amyloid-β and cerebrovascular pathology.

    Directory of Open Access Journals (Sweden)

    Panayiota Papadopoulos

    Full Text Available Animal models of Alzheimer's disease (AD are invaluable in dissecting the pathogenic mechanisms and assessing the efficacy of potential new therapies. Here, we used the peroxisome proliferator-activated receptor gamma agonist pioglitazone in an attempt to rescue the pathogenic phenotype in adult (12 months and aged (>18 months bitransgenic A/T mice that overexpress a mutated human amyloid precursor protein (APPSwe,Ind and a constitutively active form of transforming growth factor-β1 (TGF-β1. A/T mice recapitulate the AD-related cognitive deficits, amyloid beta (Aβ and cerebrovascular pathologies, as well as the altered metabolic and vascular coupling responses to increased neuronal activity. Pioglitazone normalized neurometabolic and neurovascular coupling responses to sensory stimulation, and reduced cortical astroglial and hippocampal microglial activation in both age groups. Spatial learning and memory deficits in the Morris water maze were not rescued by pioglitazone, but reversal learning was improved in the adult cohort notwithstanding a progressing Aβ pathology. While pioglitazone preserved the constitutive nitric oxide synthesis in the vessel wall, it unexpectedly failed to restore cerebrovascular reactivity in A/T mice and even exacerbated the dilatory deficits. These data demonstrate pioglitazone's efficacy on selective AD hallmarks in a complex AD mouse model of comorbid amyloidosis and cerebrovascular pathology. They further suggest a potential benefit of pioglitazone in managing neuroinflammation, cerebral perfusion and glucose metabolism in AD patients devoid of cerebrovascular pathology.

  15. Replicate study design in bioequivalency assessment, pros and cons: bioavailabilities of the antidiabetic drugs pioglitazone and glimepiride present in a fixed-dose combination formulation.

    Science.gov (United States)

    Karim, Aziz; Zhao, Zhen; Slater, Margaret; Bradford, Dawn; Schuster, Jennifer; Laurent, Aziz

    2007-07-01

    An open-label, randomized, 2-sequence, 4-period crossover (7-day washout period between treatment), replicate design study was conducted in 37 healthy subjects to assess intersubject and intrasubject variabilities in the peak (Cmax) and total (AUC) exposures to 2 oral antidiabetic drugs, pioglitazone and glimepiride, after single doses of 30 mg pioglitazone and 4 mg glimepiride, given under fasted state, as commercial tablets coadministered or as a single fixed-dose combination tablet. Variabilities for AUC(infinity) for coadministered and fixed-dose combination treatments were similar: 16% to 19% (intra) and 23% to 25% (inter) for pioglitazone and 18% to 19% (intra) and 29% to 30% for glimepiride (inter, excluding 1 poor metabolizer). Fixed-dose combination/coadministered least squares mean ratios of >or=0.86 and the 90% confidence intervals of these ratios for pioglitazone and glimepiride of between 0.80 and 1.25 for Cmax, AUC(lqc), and AUC(infinity) met the bioequivalency standards. Gender analysis showed that women showed mean of 16% and 30% higher exposure than men for glimepiride (excluding 1 poor metabolizer) and pioglitazone, respectively. There was considerable overlapping in the AUC(infinity) values, making gender-dependent dosing unnecessary. Patients taking pioglitazone and glimepiride as cotherapy may replace their medication with a single fixed-dose combination tablet containing these 2 oral antidiabetic drugs.

  16. Comparison of the efficacy of cardamom (Elettaria cardamomum with pioglitazone on dexamethasone-induced hepatic steatosis, dyslipidemia, and hyperglycemia in albino rats

    Directory of Open Access Journals (Sweden)

    G M Nitasha Bhat

    2015-01-01

    Full Text Available To evaluate the efficacy of cardamom with pioglitazone on dexamethasone-induced hepatic steatosis, dyslipidemia, and hyperglycemia in albino rats. There were four groups of 6 rats each. First group received dexamethasone alone in a dose of 8 mg/kg intraperitoneally for 6 days to induce metabolic changes and considered as dexamethasone control. Second group received cardamom suspension 1 g/kg/10 mL of 2% gum acacia orally 6 days before dexamethasone and 6 days during dexamethasone administration. Third group received pioglitazone 45 mg/kg orally 6 days before dexamethasone and 6 days during dexamethasone administration. Fourth group did not receive any medication and was considered as normal control. Fasting blood sugar, lipid profile, blood sugar 2 h after glucose load, liver weight, liver volume were recorded, and histopathological analysis was done. The effects of cardamom were compared with that of pioglitazone. Dexamethasone caused hepatomegaly, dyslipidemia and hyperglycemia. Both pioglitazone and cardamom significantly reduced hepatomegaly, dyslipidemia, and hyperglycemia (P < 0.01. Reduction of blood sugar levels after glucose load was significant with pioglitazone in comparison to cardamom (P < 0.01. Cardamom has comparable efficacy to pioglitazone in preventing dexamethasone-induced hepatomegaly, dyslipidemia, and fasting hyperglycemia.

  17. Long-term effects of pioglitazone on first attack of ischemic cerebrovascular disease in older people with type 2 diabetes: A case-control study in Taiwan.

    Science.gov (United States)

    Lai, Shih-Wei; Lin, Hsien-Feng; Lin, Cheng-Li; Liao, Kuan-Fu

    2016-08-01

    Long-term studies demonstrating the effect of pioglitazone use on primary prevention of ischemic cerebrovascular disease in older people with type 2 diabetes mellitus are lacking. This study investigated the relationship between pioglitazone use and first attack of ischemic cerebrovascular disease in Taiwan.We conducted a case-control study using the database of the Taiwan National Health Insurance Program. There were 2359 type 2 diabetic subjects aged ≥65 years with newly diagnosed ischemic cerebrovascular disease from 2005 to 2011 as the case group and 4592 sex- and age-matched, randomly selected type 2 diabetic subjects aged ≥65 years without ischemic cerebrovascular disease as the control group. The odds ratio (OR) with 95% confidence interval (CI) of ischemic cerebrovascular disease associated with pioglitazone use was measured by the multivariable unconditional logistic regression model.After adjustment for confounding factors, the multivariable logistic regression analysis disclosed that the adjusted ORs of first attack of ischemic cerebrovascular disease associated with cumulative duration of using pioglitazone were 3.34 for pioglitazone use does not have a protective effect on primary prevention for ischemic cerebrovascular disease among older people with type 2 diabetes mellitus during the first 3 years of use. Whether using pioglitazone for >3 years would have primary prevention for ischemic cerebrovascular disease needs a long-term research to prove.

  18. Suppressive effect of pioglitazone, a PPAR gamma ligand, on azoxymethane-induced colon aberrant crypt foci in KK-Ay mice.

    Science.gov (United States)

    Ueno, Toshiya; Teraoka, Naoya; Takasu, Shinji; Nakano, Katsuya; Takahashi, Mami; Yamamoto, Masafumi; Fujii, Gen; Komiya, Masami; Yanaka, Akinori; Wakabayashi, Keiji; Mutoh, Michihiro

    2012-01-01

    Obesity is an established risk factor for colorectal cancer. Pioglitazone is a peroxisome proliferator- activated receptor γ(PPARγ) agonist that induces differentiation in adipocytes and induces growth arrest and/or apoptosis in vitro in several cancer cell lines. In the present study, we investigated the effect of pioglitazone on the development of azoxymethane-induced colon aberrant crypt foci (ACF) in KK-Ay obesity and diabetes model mice, and tried to clarify mechanisms by which the PPARγ ligand inhibits ACF development. Administration of 800 ppm pioglitazone reduced the number of colon ACF / mouse to 30% of those in untreated mice and improved hypertrophic changes of adipocytes in KK-Ay mice with significant reduction of serum triglyceride and insulin levels. Moreover, mRNA levels of adipocytokines, such as leptin, monocyte chemoattractant protein-1 and plasminogen activator inhibitor-1, in the visceral fat were decreased. PCNA immunohistochemistry revealed that pioglitazone treatment suppressed cell proliferation in the colorectal epithelium with elevation of p27 and p53 gene expression. These results suggest that pioglitazone prevented obesity-associated colon carcinogenesis through improvement of dysregulated adipocytokine levels and high serum levels of triglyceride and insulin, and increase of p27 and p53 mRNA levels in the colorectal mucosa. These data indicate that pioglitazone warrants attention as a potential chemopreventive agent against obesity-associated colorectal cancer.

  19. Modulating effects of omega-3 fatty acids and pioglitazone combination on insulin resistance through toll-like receptor 4 in type 2 diabetes mellitus.

    Science.gov (United States)

    Eraky, Salma M; Abdel-Rahman, Noha; Eissa, Laila A

    2017-06-17

    Toll-like receptor 4 (TLR-4) plays important roles in innate immunity. Changes in the reduction-oxidation balance of tissues can lead to a pro-inflammatory state and insulin resistance. An action thought to be mediated by TLRs. Omega-3 fatty acids and Peroxisome Proliferator Activated Receptor gamma (PPAR-γ) agonists as pioglitazone are used for decreasing inflammation. The aim of this study is to investigate the anti-diabetic effects of combining omega -3 fatty acid with pioglitazone on type 2 diabetes, and the modifying effects on TLR-4. Type 2 diabetes was induced in male Sprague-Dawley rats by combination of high fat diet and low dose streptozotocin (35mg/kg). Diabetic rats were treated with omega-3 fatty acids (10% W/W diet), pioglitazone (20mg/kg), and their combination for 4 weeks. Omega-3 fatty acids and the combination treatment significantly decreased TLR-4 activation. Omega-3 fatty acids, pioglitazone, and their combination significantly decreased TLR-4 mRNA expression, hepatic malondialdehyde, total cholesterol and triglycerides levels, compared to diabetic group. Pioglitazone and the combination significantly decreased blood glucose levels and improved insulin resistance. In conclusion, combining omega-3 fatty acids with pioglitazone showed potential effects in lowering blood glucose levels and improving lipid profile and insulin resistance. Such effects are mediated through modulation of TLR-4. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Effects of bed-time insulin versus pioglitazone on abdominal fat accumulation, inflammation and gene expression in adipose tissue in patients with type 2 diabetes.

    Science.gov (United States)

    Hartemann-Heurtier, Agnès; Halbron, Marine; Golmard, Jean-Louis; Jacqueminet, Sophie; Bastard, Jean-Philippe; Rouault, Christine; Ayed, Amine; Pieroni, Laurence; Clément, Karine; Grimaldi, André

    2009-10-01

    Intra-abdominal fat (IAF) and inflammatory markers are correlated with cardio-vascular risk. We compared the impact of bed-time insulin versus pioglitazone treatment on these parameters in type 2 diabetic (T2D) patients. Twenty-eight T2D patients poorly controlled with metformin and sulfonylurea were randomized to receive add-on therapy with pioglitazone or bed-time NPH insulin. IAF and subcutaneous fat (SCF) content, systemic low-grade inflammation level and expression of inflammation related genes in SCF, were measured before and after 24 weeks of treatment. Insulin and pioglitazone resulted in a significant decrease in HbA1c (-1.6% and -1.2%, respectively) and a significant increase in total body fat mass (1+/-2.3 and 3.3+/-2.7 kg, respectively). There was no change in IAF content after both treatments whereas significant increase in SCF content was only seen after pioglitazone treatment (pinsulin). hsCRP level decreased after pioglitazone and ferritin level decreased after insulin treatment. No change in mRNA expression of inflammation related genes was found after either treatment. This suggests that a 24-week treatment with pioglitazone or bed-time insulin has a similar impact on intra-abdominal fat mass and systemic low-grade inflammation.

  1. [Synopsis about the hypothesis of "information channel" of channel-collateral system].

    Science.gov (United States)

    Chang, Xi-Lang

    2008-10-01

    The author of the present paper founded a theorem about the "incompleteness of single channel structure" (nerve, blood vessel, lymphatic, interspace, aperture, etc.) through quantitative and qualitative analysis about the economic information channel in the human body, which eliminates the probability of single channel structure in the information channel of channel (meridian)-collateral system. After comprehensive analysis on the current researches, the author puts forward a neodoxy, i.e., the body "information channel" structure of the channel-collateral system, mainly follows the distribution regularity of systemic statistics, and is not a single specific entity; various layers of the information channel in the main stems of the channel-collaterals are composed of optimized structure tissues. Hence, the structure of this information channel of channel-collateral system is an overall-optimized, sequential and compatible systemic structure. From this neodoxy, the author brings forward a working principle of channel-collaterals, which is supported theoretically by bio-auxology. The longitudinal distribution of the main stems of meridian-collaterals is considered to result from that in the process of the animal evolution, in the animals moving forward, the microscopic complicated movement of intracorporeal information and energy molecules is related to the forward macroscopic and non-uniform movement of organism in trans-measure. Its impulse and kinetic momentum forms a main vector in the longitudinal direction of the body (the direction of the main stem of channel-collaterals). In order to adapt to and utilize natural regularities, the main stems of the channel-collaterals gradually differentiate and evolve in the living organism, forming a whole system. The "hypothesis of biological origin of channel-collateral system" and "that of information channel of the channel-collaterals in the body" constitute a relatively complete theoretical system framework.

  2. The association of circulating monocyte count with coronary collateral growth in patients with diabetes mellitus.

    Science.gov (United States)

    Kocaman, Sinan Altan; Sahinarslan, Asife; Akyel, Ahmet; Timurkaynak, Timur; Boyaci, Bulent; Cengel, Atiye

    2010-03-01

    The status of inflammation may affect the collateral development in patients with diabetes mellitus (DM). Monocytes were found to have an important role in collateral growth in animal studies. We aimed to investigate the possible association of circulating monocyte count with collateral development in patients with DM and severe coronary artery disease (CAD). We enrolled 134 consecutive patients with DM who had > or =95 stenosis in at least one major coronary artery and investigated the relationship between circulating monocyte count and collateral growth. When we analyzed the coronary angiograms of eligible patients, we found that 64 of them had good collateral growth and 70 had poor collateral growth according to the Cohen-Rentrop method. The monocyte count was significantly different between good and poor collateral growth groups (643 +/- 184 vs. 479 +/- 143 per mm(3), P < 0.001). In the analysis comparing the Rentrop score with the Gensini score and circulating monocyte count, we found significant correlations (r = 0.293, P = 0.001 and r = 0.455, P < 0.001, respectively). The duration of ischemic symptoms tended to be longer in the good collateral group (1.9 +/- 4.1 vs. 0.8 +/- 1.3 years, P = 0.079). The Gensini score was also correlated with the duration of myocardial ischemic symptoms (r = 0.299, P = 0.004). Multivariate analysis revealed an increased monocyte count in the good collateral group [odds ratio (OR), 5.726; 95% confidence interval (CI), 1.817-18.040, P = 0.003, the cut-off value for monocyte was defined as 550 cell/mm(3)]. The increased circulating monocyte count in diabetic patients was evidently related to good coronary collateral growth. This finding may be potentially important in clinical and basic cardiovascular medicine.

  3. Relationship Between Collateral Status, Contrast Transit, and Contrast Density in Acute Ischemic Stroke.

    Science.gov (United States)

    Kawano, Hiroyuki; Bivard, Andrew; Lin, Longting; Spratt, Neil J; Miteff, Ferdinand; Parsons, Mark W; Levi, Christopher R

    2016-03-01

    Collateral circulation is recognized to influence the life expectancy of the ischemic penumbra in acute ischemic stroke. The best method to quantify collateral status on acute imaging is uncertain. We aimed to determine the relationship between visual collateral status, quantitative collateral assessments, baseline computed tomographic perfusion measures, and tissue outcomes on follow-up imaging. Sixty-six consecutive patients with acute ischemic stroke clinically eligible for recanalization therapy and with M1 or M2 middle cerebral artery occlusion were evaluated. We compared the visual collateral scoring with measures of contrast peak time delay and contrast peak density. We also compared these measures for their ability to predict perfusion lesion and infarct core volumes, final infarct, and infarct growth. Shorter contrast peak time delay (P=0.041) and higher contrast peak density (P=0.002) were associated with good collateral status. Shorter contrast peak time delay correlated with higher contrast peak density (β=-4.413; P=0.037). In logistic regression analysis after adjustment for age, sex, onset-computed tomographic time, and occlusion site, higher contrast peak density was independently associated with good collateral status (P=0.009). Multiple regression analysis showed that higher contrast peak density was an independent predictor of smaller perfusion lesion volume (P=0.029), smaller ischemic core volume (P=0.044), smaller follow-up infarct volume (P=0.005), and smaller infarct growth volume (P=0.010). Visual collateral status, contrast peak density, and contrast peak time delay were inter-related, and good collateral status was strongly associated with contrast peak density. Contrast peak density in collateral vessel may be an important factor in tissue fate in acute ischemic stroke. © 2016 American Heart Association, Inc.

  4. Effects of sitagliptin or metformin added to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients.

    Science.gov (United States)

    Derosa, Giuseppe; Maffioli, Pamela; Salvadeo, Sibilla A T; Ferrari, Ilaria; Ragonesi, Pietro D; Querci, Fabrizio; Franzetti, Ivano G; Gadaleta, Gennaro; Ciccarelli, Leonardina; Piccinni, Mario N; D'Angelo, Angela; Cicero, Arrigo F G

    2010-06-01

    The aim of the study was to compare the effects of the addition of sitagliptin or metformin to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients on body weight, glycemic control, beta-cell function, insulin resistance, and inflammatory state parameters. One hundred fifty-one patients with uncontrolled type 2 diabetes mellitus (glycated hemoglobin [HbA(1c)] >7.5%) in therapy with pioglitazone 30 mg/d were enrolled in this study. We randomized patients to take pioglitazone 30 mg plus sitagliptin 100 mg once a day, or pioglitazone 15 mg plus metformin 850 mg twice a day. We evaluated at baseline and after 3, 6, 9, and 12 months these parameters: body weight, body mass index, HbA(1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), homeostasis model assessment beta-cell function index, fasting plasma proinsulin (Pr), Pr/FPI ratio, adiponectin, resistin (R), tumor necrosis factor-alpha (TNF-alpha), and high-sensitivity C-reactive protein. A decrease of body weight and body mass index was observed with metformin, but not with sitagliptin, at the end of the study. We observed a comparable significant decrease of HbA(1c), FPG, and PPG and a significant increase of homeostasis model assessment beta-cell function index compared with baseline in both groups without any significant differences between the 2 groups. Fasting plasma insulin, fasting plasma Pr, Pr/FPI ratio, and HOMA-IR values were decreased in both groups even if the values obtained with metformin were significantly lower than the values obtained with sitagliptin. There were no significant variations of ADN, R, or TNF-alpha with sitagliptin, whereas a significant increase of ADN and a significant decrease of R and TNF-alpha values were recorded with metformin. A significant decrease of high-sensitivity C-reactive protein value was obtained in both groups without any

  5. Medial collateral ligament reconstruction in the baseball Pitcher's elbow.

    Science.gov (United States)

    Erne, Holger C; Zouzias, Ioannis C; Rosenwasser, Melvin P

    2009-08-01

    Pitchers are prone to elbow injuries because of high and repetitive valgus stresses on the elbow. The anterior bundle of the medial ulnar collateral ligament (MCL) of the elbow is the primary restraint and is often attenuated with time, leading to functional incompetence and ultimate failure. Pitchers with a history of medial elbow pain, reduced velocity, and loss of command may have an MCL injury in evolution. Physical examination and imaging can confirm the diagnosis. Treatment begins with rest and activity modification. All medial elbow pain is not MCL injury. Surgery is considered only for talented athletes who wish to return to competitive play and may include elite scholastic and other collegiates and professionals. The technique for MCL reconstruction was first described in 1986. Many variations have been offered since then, which can result in predictable outcomes, allowing many to return to the same level of competitive play.

  6. On Security of Collateral in Danish Mortgage Finance

    DEFF Research Database (Denmark)

    Haldrup, Karin

    2017-01-01

    on the balance principle that assigns risks and responsibility to market players in a self-disciplinary manner and protected the mortgage banks against cash flow mismatches even during deep crisis, as history attests. It is shown how property registers and effective enforcement have created transparent property......Specialized mortgage intermediaries in Denmark have for over two hundred years provided owners and buyers of real property wide access to credit. The present paper sets out to explore the safeguards that nurtured development of a robust, market based financing system and a deep mortgage market....... Observations are made on the nature of collateral performance in respect to property rights, mortgage law and market development in search of general features of required institutional arrangements. The robustness of the Danish mortgage finance system is largely accredited to the securitization model based...

  7. Stress changes of lateral collateral ligament at different

    Directory of Open Access Journals (Sweden)

    ZHONG Yan-lin

    2011-04-01

    Full Text Available 【Abstract】 Objective: To create a 3-dimensional finite element model of knee ligaments and to analyse the stress changes of lateral collateral ligament (LCL with or without displaced movements at different knee flexion conditions. Methods: A four-major-ligament contained knee specimen from an adult died of skull injury was prepared for CT scanning with the detectable ligament insertion footprints, locations and orientations precisely marked in advance. The CT scanning images were converted to a 3-dimensional model of the knee with the 3-dimensional reconstruction technique and transformed into finite element model by the software of ANSYS. The model was validated using experimental and numerical results obtained by other scientists. The natural stress changes of LCL at five different knee flexion angles (0°, 30°, 60°, 90°, 120° and under various motions of anterior-posterior tibial translation, tibial varus rotation and internal-external tibial rotation were measured. Results: The maximum stress reached to 87%-113% versus natural stress in varus motion at early 30° of knee flexions. The stress values were smaller than the peak value of natural stress at 0° (knee full extension when knee bending was over 60° of flexion in anterior-posterior tibial translation and internal-external rotation. Conclusion: LCL is vulnerable to varus motion in almost all knee bending positions and susceptible to anterior- posterior tibial translation or internal-external rotation at early 30° of knee flexions. Key words: Knee joint; Collateral ligaments; Finite element analysis

  8. Effects of intensive insulin therapy alone and in combination with pioglitazone on body weight, composition, distribution and liver fat content in patients with type 2 diabetes.

    Science.gov (United States)

    Shah, P K; Mudaliar, S; Chang, A R; Aroda, V; Andre, M; Burke, P; Henry, R R

    2011-06-01

    To evaluate the effects of intensive insulin therapy alone and with added pioglitazone on body weight, fat distribution, lean body mass (LBM) and liver fat in type 2 diabetic patients. Twenty-five insulin-treated, obese patients with type 2 diabetes were randomized to addition of pioglitazone 45 mg (n = 12) or placebo (n = 13) and treated intensively for 12-16 weeks. Dual-energy X-ray absorptiometry/abdominal computed tomography scans were performed before/after treatment. LBM, visceral/subcutaneous adipose tissue (VAT/SAT) and liver/spleen (L/S) attenuation ratios were measured pre-/posttreatment (a ratio insulin alone and insulin + pioglitazone significantly improved glycaemic control (7.8 ± 0.3 to 7.2 ± 0.3% and 7.6 ± 0.3 to 7.1 ± 0.4%, respectively). Body weight gain was greater with insulin + pioglitazone (4.9 ± 4.5 kg) versus insulin therapy alone (1.7 ± 0.7 kg). SAT increased significantly with pioglitazone + insulin therapy (393.9 ± 48.5 to 443.2 ± 56.7 cm(2) , p insulin therapy alone (412.9 ± 42.5 to 420.8 ± 43.8 cm(2) ). VAT decreased non-significantly in both groups (240.3 ± 41.7 to 223.8 ± 38.1 cm(2) with insulin + pioglitazone and 266.6 ± 27.4 to 250.5 ± 22.2 cm(2) with insulin therapy). LBM increased significantly by 1.92 ± 0.74 kg with insulin + pioglitazone treatment. The L/S attenuation ratio in the placebo + insulin group decreased from 1.08 ± 0.1 to 1.04 ± 0.1 (p = ns) and increased from 1.00 ± 0.1 to 1.08 ± 0.05 (p = 0.06) in the pioglitazone + insulin group. Intensification of insulin therapy in type 2 diabetic patients causes modest weight gain and no change in body fat distribution, LBM or liver fat. In contrast, the addition of pioglitazone, at equivalent glycaemia, increases weight gain, fat mass and SAT; increases LBM and tends to decrease liver fat. These changes in fat distribution may contribute to the beneficial effects of pioglitazone, despite greater weight gain. Published 2011. This article is a US Government work

  9. Laparoscopic umbilical hernia repair in the presence of extensive paraumbilical collateral veins: a case report.

    Science.gov (United States)

    Lases, Seilenna S; Eker, Hasan H; Pierik, Engelbertus G J M; Klitsie, Pieter J; de Goede, Barry; Peeters, Mark P F M Vrancken; Kazemier, Geert; Lange, Johan F

    2011-12-01

    A patient with an umbilical hernia presenting with collateral veins in the abdominal wall and umbilicus is a case that every hernia surgeon has to deal with occasionally. Several underlying diseases have been described to provoke collateral veins in the abdominal wall. However, the treatment strategy should be uniform. We herein report a case of a successful laparoscopic umbilical hernia repair in a patient with collateral veins in the abdominal wall and umbilicus. A 63-year-old man was referred to the surgical outpatient clinic with a large symptomatic umbilical hernia and collateral veins in the abdominal wall, secondary to an occlusion of both common iliac veins. Because of collateral veins in the umbilicus and the size of the hernial defect, he was offered laparoscopic hernia repair without compromising these veins. Because of the extensive abdominal wall collaterals, duplex sonography vein mapping was performed preoperatively to mark a safe collateral-free area for trocar introduction. The defect was repaired by mesh prosthesis.

  10. Lateral collateral ligament deficiency of the elbow joint: A modeling approach.

    Science.gov (United States)

    Rahman, Munsur; Cil, Akin; Bogener, James W; Stylianou, Antonis P

    2016-09-01

    A computational model capable of predicting the effects of lateral collateral ligament deficiency of the elbow joint would be a valuable tool for surgical planning and prediction of the long-term consequences of ligament deficiency. The purpose of this study was to simulate lateral collateral ligament deficiency during passive flexion using a computational multibody elbow joint model and investigate the effects of ligament insufficiency on the kinematics, ligament loads, and articular contact characteristics (area, pressure). The elbow was placed initially at approximately 20° of flexion and a 345 mm vertical downward motion profile was applied over 40 s to the humerus head. The vertical displacement induced flexion from the initial position to a maximum flexion angle of 135°. The study included simulations for intact, radial collateral ligament deficient, lateral ulnar collateral ligament deficient, and combined radial and lateral ulnar collateral ligament deficient elbow. For each condition, relative bone kinematics, contact pressure, contact area, and intact ligament forces were predicted. Intact and isolated radial collateral ligament deficient elbow simulations were almost identical for all observed outcomes. Minor differences in kinematics, contact area and pressure were observed for the isolated lateral ulnar collateral ligament deficient elbow compared to the intact elbow, but no elbow dislocation was detected. However, sectioning both ligaments together induced substantial differences in kinematics, contact area, and contact pressure, and caused complete dislocation of the elbow joint. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1645-1655, 2016.

  11. Determinants and prognostic significance of collaterals in patients undergoing coronary revascularization.

    Science.gov (United States)

    Nathoe, Hendrik M; Koerselman, Jeroen; Buskens, Erik; van Dijk, Diederik; Stella, Pieter R; Plokker, Thijs H W; Doevendans, Pieter A F M; Grobbee, Diederick E; de Jaegere, Peter P T

    2006-07-01

    There is evidence that coronary collaterals improve the prognosis in patients with acute myocardial infarction (MI). However, there is limited clinical information on the protective role of collaterals in patients with stable coronary artery disease. This information may help risk stratification and the development of novel therapies, such as arteriogenesis and angiogenesis. The relation between collaterals and cardiac death or MI at 1 year after coronary revascularization was studied in 561 patients who were enrolled in a randomized study that compared stent implantation with bypass grafting. Collaterals were assessed on an angiogram using Rentrop's classification and considered present with a Rentrop grade >1. Unadjusted and adjusted odds ratios for cardiac death or MI at 1 year were calculated using univariate and multivariate regression analyses. In addition, determinants of collaterals were assessed using univariate and multivariate analyses. Collaterals were present in 176 patients (31%). The adjusted odds ratio of cardiac death or infarction was 0.18 (95% confidence interval 0.04 to 0.78) in the presence of collaterals. Independent determinants of collaterals were age (odds ratio 0.97, 95% confidence interval 0.95 to 0.99), multivessel disease (odds ratio 1.60, 95% confidence interval 1.02 to 2.51), impaired ventricular function (odds ratio 1.85, 95% confidence interval 1.04 to 3.29), type C lesion (odds ratio 3.72, 95% confidence interval 2.33 to 5.95), and stenosis severity >90% (odds ratio 9.08, 95% confidence interval 4.65 to 17.73). In conclusion, in patients with a low risk profile, the presence of collaterals protects against cardiac death and MI at 1 year after coronary revascularization. Variables that reflect the duration and severity of the atherosclerotic and ischemic burden determine their presence.

  12. Collateral blood flow in different cerebrovascular hierarchy provides endogenous protection in cerebral ischemia.

    Science.gov (United States)

    Luo, Chuanming; Liang, Fengyin; Ren, Huixia; Yao, Xiaoli; Liu, Qiang; Li, Mingyue; Qin, Dajiang; Yuan, Ti-Fei; Pei, Zhong; Su, Huanxing

    2016-11-15

    Collateral blood flow as vascular adaptions to focal cerebral ischemia is well recognized. However, few studies directly investigate the dynamics of collateral vessel recruitment in vivo and little is known about the effect of collateral blood flow in different cerebrovascular hierarchy on the neuropathology after focal ischemic stroke. Here, we report that collateral blood flow is critically involved in blood vessel compensations following regional ischemia. We occluded a pial arteriole using femtosecond laser ablating under the intact thinned skull and documented the changes of collateral flow around the surface communication network and between the surface communication network and subsurface microcirculation network using in vivo two photon microscopy imaging. Occlusion of the pial arteriole apparently increased the diameter and collateral blood flow of its leptomeningeal anastomoses, which significantly reduced the cortical infarction size. This result suggests that the collateral flow via surface communicating network connected with leptomeningeal anastomoses could greatly impact on the extent of infarction. We then further occluded the target pial arteriole and all of its leptomeningeal anastomoses. Notably, this type of occlusion led to reversals of blood flow in the penetrating arterioles mainly proximal to the occluded pial arteriole in a direction from the subsurface microcirculation network to surface arterioles. Interesting, the cell death in the area of ischemic penumbra was accelerated when we performed occlusion to cease the reversed blood flow in those penetrating arterioles, suggesting that the collateral blood flow from subsurface microcirculation network exerts protective roles in delaying cell death in the ischemic penumbra. In conclusion, we provide the first experimental evidence that collateral blood vessels at different cerebrovascular hierarchy are endogenously compensatory mechanisms in brain ischemia. This article is protected by

  13. Leptomeningeal collateralization in acute ischemic stroke: Impact on prominent cortical veins in susceptibility-weighted imaging

    Energy Technology Data Exchange (ETDEWEB)

    Verma, Rajeev K., E-mail: rajeev.verma@insel.ch [University Institute for Diagnostic and Interventional Neuroradiology, Inselspital, University of Bern, Bern (Switzerland); Hsieh, Kety; Gratz, Pascal P.; Schankath, Adrian C.; Mordasini, Pasquale; Zubler, Christoph; Kellner-Weldon, Frauke [University Institute for Diagnostic and Interventional Neuroradiology, Inselspital, University of Bern, Bern (Switzerland); Jung, Simon [Department of Neurology, Inselspital, University of Bern, Bern (Switzerland); Schroth, Gerhard; Gralla, Jan; El-Koussy, Marwan [University Institute for Diagnostic and Interventional Neuroradiology, Inselspital, University of Bern, Bern (Switzerland)

    2014-08-15

    Background: The extent of hypoperfusion is an important prognostic factor in acute ischemic stroke. Previous studies have postulated that the extent of prominent cortical veins (PCV) on susceptibility-weighted imaging (SWI) reflects the extent of hypoperfusion. Our aim was to investigate, whether there is an association between PCV and the grade of leptomeningeal arterial collateralization in acute ischemic stroke. In addition, we analyzed the correlation between SWI and perfusion-MRI findings. Methods: 33 patients with acute ischemic stroke due to a thromboembolic M1-segment occlusion underwent MRI followed by digital subtraction angiography (DSA) and were subdivided into two groups with very good to good and moderate to no leptomeningeal collaterals according to the DSA. The extent of PCV on SWI, diffusion restriction (DR) on diffusion-weighted imaging (DWI) and prolonged mean transit time (MTT) on perfusion-imaging were graded according to the Alberta Stroke Program Early CT Score (ASPECTS). The National Institutes of Health Stroke Scale (NIHSS) scores at admission and the time between symptom onset and MRI were documented. Results: 20 patients showed very good to good and 13 patients poor to no collateralization. PCV-ASPECTS was significantly higher for cases with good leptomeningeal collaterals versus those with poor leptomeningeal collaterals (mean 4.1 versus 2.69; p = 0.039). MTT-ASPECTS was significantly lower than PCV-ASPECTS in all 33 patients (mean 1.0 versus 3.5; p < 0.00). Conclusions: In our small study the grade of leptomeningeal collateralization correlates with the extent of PCV in SWI in acute ischemic stroke, due to the deoxyhemoglobin to oxyhemoglobin ratio. Consequently, extensive PCV correlate with poor leptomeningeal collateralization while less pronounced PCV correlate with good leptomeningeal collateralization. Further SWI is a very helpful tool in detecting tissue at risk but cannot replace PWI since MTT detects significantly more ill

  14. Genetic variation in retinal vascular patterning predicts variation in pial collateral extent and stroke severity

    Science.gov (United States)

    Prabhakar, Pranay; Zhang, Hua; Chen, De; Faber, James E.

    2015-01-01

    The presence of a native collateral circulation in tissues lessens injury in occlusive vascular diseases. However, differences in genetic background cause wide variation in collateral number and diameter in mice, resulting in large variation in protection. Indirect estimates of collateral perfusion suggest wide variation also exists in humans. Unfortunately, methods used to obtain these estimates are invasive and not widely available. We sought to determine if differences in genetic background in mice result in variation in branch-patterning of the retinal arterial circulation, and if these differences predict strain-dependent differences in pial collateral extent and severity of ischemic stroke. Retinal patterning metrics, collateral extent, and infarct volume were obtained for 10 strains known to differ widely in collateral extent. Multivariate regression was conducted and model performance assessed using K-fold cross-validation. Twenty-one metrics varied with strain (placunarity, optimality) predicted collateral number and diameter across 7 regression models, with the best model closely predicting (p<0.0001) number (± 1.2-3.4 collaterals, K-fold R2=0.83-0.98), diameter (± 1.2-1.9μm, R2=0.73-0.88) and infarct volume (± 5.1 mm3, R2=0.85-0.87). These metrics obtained for the middle cerebral artery tree in a subset of the above strains also predicted (p<0.0001) collateral number and diameter and diameter, although with less strength (K-fold R2=0.61-0.78) and 0.60-0.86, respectively). Thus, differences in arterial branch-patterning in the retina and the MCA trees are specified by genetic background and predict variation in collateral extent and stroke severity. If also true in human retina, and since genetic variation in cerebral collaterals extends to other tissues at least in mice, a similar “retinal predictor index” could serve as a non-or minimally invasive biomarker for collateral extent in brain and other tissues. This could aid prediction of severity

  15. Injuries to the Collateral Ligaments of the Metacarpophalangeal Joint of the Thumb, Including Simultaneous Combined Thumb Ulnar and Radial Collateral Ligament Injuries, in National Football League Athletes.

    Science.gov (United States)

    Werner, Brian C; Belkin, Nicole S; Kennelly, Steve; Weiss, Leigh; Barnes, Ronnie P; Rodeo, Scott A; Warren, Russell F; Hotchkiss, Robert N

    2017-01-01

    Thumb collateral ligament injuries occur frequently in the National Football League (NFL). In the general population or in recreational athletes, pure metacarpophalangeal (MCP) abduction or adduction mechanisms yield isolated ulnar collateral ligament (UCL) and radial collateral ligament (RCL) tears, respectively, while NFL athletes may sustain combined mechanism injury patterns. To evaluate the incidence of simultaneous combined thumb UCL and RCL tears among all thumb MCP collateral ligament injuries in NFL athletes on a single team. Case series; Level of evidence, 4. A retrospective review of all thumb injuries on a single NFL team from 1991 to 2014 was performed. All players with a thumb MCP collateral ligament injury were included. Collateral ligament injuries were confirmed by review of both physical examination findings and magnetic resonance imaging. Player demographics, surgical details, and return-to-play data were obtained from the team electronic medical record and surgeons' records. A total of 36 thumbs in 32 NFL players were included in the study, yielding an incidence of 1.6 thumb MCP collateral ligament injuries per year on a single NFL team. Of these, 9 thumbs (25%) had a simultaneous combined UCL and RCL tear injury pattern confirmed on both physical examination and MRI. The remaining 27 thumbs (75%) were isolated UCL injuries. All combined UCL/RCL injuries required surgery due to dysfunction from instability; 63.0% of isolated UCL injuries required surgical repair ( P = .032) due to continued pain and dysfunction from instability. Repair, when required, was delayed until the end of the season. All players with combined UCL/RCL injuries and isolated UCL injuries returned to play professional football the following season. Simultaneous combined thumb UCL and RCL tear is a previously undescribed injury pattern that occurred in 25% of thumb MCP collateral ligament injuries on a single NFL team over a 23-year period. All players with combined thumb UCL

  16. Pioglitazone utilization, efficacy & safety in Indian type 2 diabetic patients: A systematic review & comparison with European Medicines Agency Assessment Report

    Directory of Open Access Journals (Sweden)

    Sarayu A Pai

    2016-01-01

    Interpretation & conclusions: In India, probably due to lower dose, lower background incidence of bladder cancer and smaller sample size in epidemiological studies, association of bladder cancer with pioglitazone was not found to be significant. Reporting of CTs and adverse drug reactions to Clinical Trials Registry of India and Pharmacovigilance Programme of India, respectively, along with compliance studies with warning given in package insert and epidemiological studies with larger sample size are needed.

  17. PPAR-γ2 and PTPRD gene polymorphisms influence type 2 diabetes patients' response to pioglitazone in China

    Institute of Scientific and Technical Information of China (English)

    Qi PEI; Zhao-qian LIU; Qiong HUANG; Guo-ping YANG; Ying-chun ZHAO; Ji-ye YIN; Min SONG; Yi ZHENG; Zhao-hui MO; Hong-hao ZHOU

    2013-01-01

    Aim: To investigate the influence of peroxisome proliferator-activated receptor y2 (PPAR-Y2) gene polymorphism rs1801282 and protein tyrosine phosphatase receptor type D (PTPRD) gene polymorphism rs17584499 on the occurrence of type 2 diabetes and pioglitazone efficacy in a Chinese Han population.Methods: One hundred ninety seven type 2 diabetes patients and 212 healthy controls were enrolled.Among them,67 type 2 diabetes patients were administered pioglitazone (30 mg/d,po) for 3 months.All the subjects were genotyped for genetic variants in PPAR-γ2 and PTPRD using MALDI-TOF mass spectrometry.Fasting plasma glucose,postprandial plasma glucose,glycated hemoglobin,serum triglyceride,total cholesterol,low-density and high-density lipoprotein-cholesterol were determined.Results: The PPAR-y2 gene rs1801282 polymorphism was significantly associated with type 2 diabetes susceptibility (OR=0.515,95% CI 0.268-0.990) and the PTPRD gene rs17584499 polymorphism was also significantly associated with type 2 diabetes (OR=1.984,95% Cl 1.135-3.469) in a dominant model adjusted for age,gender and BMI.After pioglitazone treatment for 3 months,the type 2 diabetes patients with PPAR-γ2 rs1801282 CG genotypes significantly showed higher differential values of postprandial plasma glucose and serum triglyceride compared with those with rs1801282 CC genotype.The patients with PTPRD rs17584499 CT+TT genotypes showed significantly lower differential value of postprandial plasma glucose compared to those with rs17584499 CC genotype.Conclusion: Diabetes risk alleles in PPAR-y2 (rs1801282) and PTPRD (rs17584499) are associated with pioglitazone therapeutic efficacy.

  18. Adiponectin gene polymorphism rs2241766 T/G is associated with response to pioglitazone treatment in type 2 diabetic patients from southern China.

    Directory of Open Access Journals (Sweden)

    Hong Yang

    Full Text Available INTRODUCTION: Insulin sensitizing drugs such as pioglitazone are not uniformly treatment effective among individual type 2 diabetic patients. Here, the relationship of pioglitazone efficacy to single nucleotide polymorphisms (SNP of the adiponectin gene, a critical gene directly regulated by the drug, was examined in a cohort of Chinese Han type 2 diabetic patients. METHODS: Eighty type 2 diabetic patients were treated with pioglitazone (15 mg/day for 12 weeks without interruption of their current therapeutic regimen. Fasting plasma glucose, fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR, and glycated hemoglobin (HbA1c% were collected both prior to and following pioglitazone treatment. Response to pioglitazone was defined as a decrease of at least 15% in HbA1c% levels. Three regions of the adiponectin gene containing SNPs (promoter, intron 2 and exon 2, and exon 3 were amplified and sequenced to determine genotype. RESULTS: Serum adiponectin levels were significantly increased (p<0.001 whereas fasting plasma glucose, fasting insulin, HOMA-IR, and HbA1c% values were significantly decreased relative to baseline measurements (p<0.001. Response of patients with TG and TT genotypes at rs2241766 (exon2; 52.9% vs. 12.7%, respectively p = 0.001 was statistically significant relative to all other patients. Amongst rs2241766 TG and TT patients, the mean decrease in HbA1c% levels was greater where the genotype was TG (1.15±0.80 vs. 0.52±0.64, p = 0.001. CONCLUSIONS: The adiponectin gene polymorphism rs2241766 T/G is associated with pioglitazone efficacy in type 2 diabetic patients, and status of the polymorphism may be an important clinical factor to consider prior to pioglitazone treatment.

  19. Pioglitazone inhibits the expression of nicotinamide adenine dinucleotide phosphate oxidase and p38 mitogen-activated protein kinase in rat mesangial cells

    Institute of Scientific and Technical Information of China (English)

    WANG Shan; YE Shan-dong; SUN Wen-jia; HU Yuan-yuan

    2013-01-01

    Background Oxidative Stress and p38 mitogen-activated protein kinase (p38MAPK) play a vital role in renal fibrosis.Pioglitazone can protect kidney but the underlying mechanisms are less clear.The purpose of this study was to investigate the effect of pioglitazone on oxidative stress and whether the severity of oxidative stress was associated with the phosphorylation level of p38MAPK.Methods Rat mesangial cells were cultured and randomly assigned to control group,high glucose group and pioglitazone group.After 48-hour exposure,the supernatants and ceils were collected.The protein levels of p22phox,p47phox,phosphorylated p38MAPK,total p38MAPK were measured by Western blotting.The gene expressions of p22phox,p47phox were detected by RT-PCR.The levels of intracellular reactive oxygen species (ROS) were determined by flow cytometry.The levels of superoxide dismutase (SOD) and maleic dialdehyde (MDA) in the supernatant were determined respectively.Results Compared with the control group,the expression levels of p22phox,p47phox,phospho-p38 and ROS significantly increased,activity of SOD decreased in high glucose group,while the level of MDA greatly increased (P <0.01).Pioglitazone significantly suppressed p22phox,p47phox expressions and oxidative stress induced by high glucose.The expressions of p22phox,p47phox,phospho-p38MAPK and ROS generation were markedly reduced after pioglitazone treatment (P <0.05).The activity of SOD in the the supernatant increased (P <0.05),while the level of MDA decreased greatly by pioglitazone (P <0.05).The level of oxidative stress was associated with the phosphorylation level of p38MAPK (P <0.01).Conclusion Pioglitazone can inhibit oxidative stress through suppressing NADPH oxidase expression and p38MAPK phosphorylation.

  20. The Effects of Sub-Chronic Treatment with Pioglitazone on the Septic Mice Mortality in the Model of Cecal Ligation and Puncture: Involvement of Nitric Oxide Pathway

    Directory of Open Access Journals (Sweden)

    Hamed Shafaroodi

    2015-10-01

    Full Text Available Sepsis is a systemic inflammatory response syndrome caused by an infection and remains as a major challenge in health care. Many studies have reported that pioglitazone may display anti-inflammatory effects. This study was designed to evaluate the effect of subchronic treatment with pioglitazone on high-grade septic mice survival and nitrergic system involvement. Diffused sepsis was induced by cecal ligation and puncture (CLP surgery in male NMRI mice (20-30 g. Pioglitazone (5,10 and 20 mg/kg was administered by gavage daily for 5 days prior to surgery. Nitric oxide involvement was assessed by sub-chronic administration of a non-selective nitric oxide synthase inhibitor, L-NAME and a selective inducible nitric oxide synthase inhibitor, aminoguanidine. TNF-α  and IL-1β plasma levels were measured by ELISA. Pioglitazone (10 and 20 mg/kg significantly improved survival rate in septic mice. The chronic intraperitoneally co-administration of L-NAME (0.5 mg/kg, daily or aminoguanidine (1 mg/kg, daily with a daily dose of pioglitazone, 5 mg/kg, significantly increased the survival rate. This survival improving effect was accompanied by a significant reduction in pro-inflammatory cytokines TNF-α and IL-1β plasma levels. In conclusion, sub-chronic pioglitazone treatment can improve survival in mouse sepsis model by CLP. Inhibition of nitric oxide release, probably through inducible nitric oxide synthase at least in part is responsible for this effect. Suppression of TNF-α and IL-1β could be another mechanism in pioglitazone-induced survival improving effect in septic mice.

  1. The Effects of Sub-Chronic Treatment with Pioglitazone on the Septic Mice Mortality in the Model of Cecal Ligation and Puncture: Involvement of Nitric Oxide Pathway.

    Science.gov (United States)

    Shafaroodi, Hamed; Hassanipour, Mahsa; Mousavi, Zahra; Rahimi, Nastaran; Dehpour, Ahmad Reza

    2015-10-01

    Sepsis is a systemic inflammatory response syndrome caused by an infection and remains as a major challenge in health care. Many studies have reported that pioglitazone may display anti-inflammatory effects. This study was designed to evaluate the effect of subchronic treatment with pioglitazone on high-grade septic mice survival and nitrergic system involvement. Diffused sepsis was induced by cecal ligation and puncture (CLP) surgery in male NMRI mice (20-30 g). Pioglitazone (5,10 and 20 mg/kg) was administered by gavage daily for 5 days prior to surgery. Nitric oxide involvement was assessed by sub-chronic administration of a non-selective nitric oxide synthase inhibitor, L-NAME and a selective inducible nitric oxide synthase inhibitor, aminoguanidine. TNF-α  and IL-1β plasma levels were measured by ELISA. Pioglitazone (10 and 20 mg/kg) significantly improved survival rate in septic mice. The chronic intraperitoneally co-administration of L-NAME (0.5 mg/kg, daily) or aminoguanidine (1 mg/kg, daily) with a daily dose of pioglitazone, 5 mg/kg, significantly increased the survival rate. This survival improving effect was accompanied by a significant reduction in pro-inflammatory cytokines TNF-α and IL-1β plasma levels. In conclusion, sub-chronic pioglitazone treatment can improve survival in mouse sepsis model by CLP. Inhibition of nitric oxide release, probably through inducible nitric oxide synthase at least in part is responsible for this effect. Suppression of TNF-α and IL-1β could be another mechanism in pioglitazone-induced survival improving effect in septic mice.

  2. Pioglitazone does not increase the risk of type II diabetes in patients with bladder cancer: A retrospective study.

    Science.gov (United States)

    Dong, Youhong; Wang, Anping

    2016-07-01

    The aim of the retrospective study was to analyze the effect of pioglitazone on the expression of tumor tissue inflammation factor interleukin (IL)-8, macrophage colony-stimulating factor (M-CSF) and vascular endothelial growth factor (VEGF) of type II diabetes in bladder cancer patients. In addition, whether there was a correlation between pioglitazone and the occurrence of male bladder cancer was also investigated. In total, 42 male cases diagnosed with type II diabetes secondary to bladder cancer were selected. Forty male cases, with simplex type II diabetes but not with bladder cancer, served as the control. Tumor biopsy specimens were collected to detect the expression levels of IL-8, M-CSF and VEGF. The results showed that the expression of IL-8, M-CSF and VEGF of the simplex diabetes group was significantly lower than that of the secondary to tumor group (Ppioglitazone, duration of diabetes, average fasting blood sugar and glycated hemoglobin levels, was not statistically significant. Multivariable logistic regression analysis revealed that the expression levels of IL-8, M-CSF and VEGF were independent risk factors for the occurrence of bladder cancer (Ppioglitazone (P>0.05). In conclusion, oral pioglitazone may not increase the risk of type II diabetes patients with bladder cancer. However, the occurrence of bladder cancer be associated with the increasing expression levels of IL-8, M-CSF and VEGF.

  3. Formulation and evaluation of sustained release matrix tablets of pioglitazone hydrochloride using processed Aloe vera mucilage as release modifier

    Directory of Open Access Journals (Sweden)

    Manoj Choudhary

    2015-01-01

    Full Text Available Background: Natural gums and mucilage which hydrates and swells on contact with aqueous media are used as additives in the formulation of hydrophilic drug delivery system. Aim: The purpose of this study was to develop a new monolithic matrix system for complete delivery of Pioglitazone hydrochloride (HCl, in a zero-order manner over an extended time period using processed Aloe vera gel mucilage (PAG as a release modifier. Materials and Methods: The matrices were prepared by dry blending of selected ratios of polymer and ingredients using direct compression technique. Physicochemical properties of dried powdered mucilage of A. vera were studied. Various formulations of pioglitazone HCl and A. vera mucilage were prepared using different drug: Polymer ratios viz., 1:1, 1:2, 1:3, 1:4, 1:5 for PAG by direct compression technique. Results: The formulated matrix tablets were found to have better uniformity of weight and drug content with low statistical deviation. The swelling behavior and in vitro release rate characteristics were also studied. Conclusion: The study proved that the dried A. vera mucilage can be used as a matrix forming material for controlled release of Pioglitazone HCl matrix tablets.

  4. The role of peroxisome proliferator-activated receptor and effects of its agonist, pioglitazone, on a rat model of optic nerve crush: PPARγ in retinal neuroprotection.

    Directory of Open Access Journals (Sweden)

    Juming Zhu

    Full Text Available It has been shown that peroxisome proliferators-activated receptor gamma (PPARγ is beneficial for central nervous system injury. However its role on optic nerve injury remains unknown. In the present study, we examined the change of PPARγ expression in rat retina following optic nerve injury and investigated the effect of pioglitazone (Pio, a PPARγ agonist, on retinal ganglion cells (RGCs neuroprotection using a rat optic nerve crush (ONC model. Our results showed that PPARγ mRNA and protein levels were increased after ONC, and most of PPARγ-immunoreactive cells colocalized with Müller cells. Pio treatment significantly enhanced the number of surviving RGCs and inhibited RGCs apoptosis induced by ONC. However, when PPARγ antagonist GW9662 was used, these neuroprotective effects were abolished. In addition, pio attenuated Müller cell activation after ONC. These results indicate that PPARγ appears to protect RGCs from ONC possibly via the reduction of Müller glial activation. It provides evidence that activation of PPARγ may be a potential alternative treatment for RGCs neuroprotection.

  5. Incidentally detected right pulmonary artery agenesis with right coronary artery collateralization.

    Science.gov (United States)

    Mikaberidze, Nino; Goldberg, Ythan; Khosraviani, Khashayar; Taub, Cynthia

    2014-01-01

    Unilateral pulmonary artery agenesis (UPAA) with pulmonary hypoplasia is a rare congenital anomaly. We describe a 71-year old male who was incidentally diagnosed with the right UPAA and a hypoplastic right lung supplied by collateralized right coronary.

  6. Heterotrophic denitrification vs. autotrophic anammox – quantifying collateral effects on the oceanic carbon cycle

    National Research Council Canada - National Science Library

    Koeve, W; Kähler, P

    2010-01-01

    .... Recently, it has been suggested that the trophic nature of pelagic N2 -production may have additional, "collateral" effects on the carbon cycle, where heterotrophic denitrification provides a shallow...

  7. Resolution of bilateral moyamoya associated collateral vessel aneurysms: Rationale for endovascular versus surgical intervention

    Directory of Open Access Journals (Sweden)

    Sepideh Amin-Hanjani

    2014-01-01

    Full Text Available Background: Management of aneurysms associated with deep collateral vessels in moyamoya disease is challenging both from an endovascular and a surgical standpoint. Difficulties with access or localization, and compromise of the collateral circulation with subsequent ischemia are the primary concerns, making direct obliteration potentially unfeasible or risky. Alternatively, superficial temporal artery-middle cerebral artery bypass is another potential strategy for resolution of these aneurysms. Case Description: Presented are the findings and management for a patient with moyamoya disease and bilateral deep collateral vessel aneurysms, successfully treated with endovascular obliteration following a right-sided hemorrhage and subsequently with bypass for an unruptured but growing contralateral aneurysm. Conclusions: A rationale and approach to management is outlined, as derived from review of the current literature and the illustrative case with bilateral collateral vessel aneurysms.

  8. Use of collateral sensitivity networks to design drug cycling protocols that avoid resistance development

    DEFF Research Database (Denmark)

    Imamovic, Lejla; Sommer, Morten

    2013-01-01

    New drug deployment strategies are imperative to address the problem of drug resistance, which is limiting the management of infectious diseases and cancers. We evolved resistance in Escherichia coli toward 23 drugs used clinically for treating bacterial infections and mapped the resulting...... and select against drug resistance development. We identified hundreds of such drug sets and demonstrated that the antibiotics gentamicin and cefuroxime can be deployed cyclically such that the treatment regimen selected against resistance to either drug. We then validated our findings with related bacterial...... collateral sensitivity and resistance profiles, revealing a complex collateral sensitivity network. On the basis of these data, we propose a new treatment framework-collateral sensitivity cycling-in which drugs with compatible collateral sensitivity profiles are used sequentially to treat infection...

  9. Hypoglycaemia with oral antidiabetic drugs: results from prescription-event monitoring cohorts of rosiglitazone, pioglitazone, nateglinide and repaglinide.

    Science.gov (United States)

    Vlckova, Veronika; Cornelius, Victoria; Kasliwal, Rachna; Wilton, Lynda; Shakir, Saad A W

    2009-01-01

    Hypoglycaemia is an acute complication associated with intensive treatment of patients with diabetes mellitus. This complication poses a major challenge in diabetes management. Furthermore, severe hypoglycaemia may be life threatening. Although hypoglycaemia is more often associated with insulin treatment, oral hypoglycaemic agents have the potential to trigger hypoglycaemia. The aim of this study was to quantify the incidence of hypoglycaemic events and to describe the pattern of these incident events during the first 9 months of treatment with four oral antidiabetic drugs, rosiglitazone, pioglitazone, nateglinide and repaglinide, prescribed in general practice in England. We used data collected for prescription-event monitoring (PEM) studies of rosiglitazone, pioglitazone, nateglinide and repaglinide. PEM is an observational, non-interventional, incept cohort study. Observation time for each patient and incidence rate (IR) per 1000 patient-years of treatment for hypoglycaemia was calculated for each drug cohort. Smoothed hazard estimates were plotted over time. Case/non-case analysis was performed to describe and compare patients who had at least one hypoglycaemic event in the first 9 months of treatment with those who did not. The total number of patients included in the analysis was 14,373, 12,768, 4,549 and 5,727 in rosiglitazone, pioglitazone, nateglinide and repaglinide cohorts, respectively. From these, 276 patients experienced at least one episode of hypoglycaemia. The IR was between 50% and 100% higher in patients receiving treatment with meglitinides compared with those treated with the thiazolidinediones (TZDs) [IR = 9.94, 9.64, 15.71 and 20.32 per 1,000 patient-years for rosiglitazone, pioglitazone, nateglinide and repaglinide, respectively]. The plot of the hazard function and the estimated shape parameter from the Weibull regression model showed that pioglitazone, nateglinide and repaglinide had non-constant (decreasing) hazards over time, whereas

  10. Efficacy of pioglitazone on glycemic control and carotid intima-media thickness in type 2 diabetes patients with inadequate insulin therapy.

    Science.gov (United States)

    Yasunari, Eisuke; Takeno, Kageumi; Funayama, Hideaki; Tomioka, Setsuko; Tamaki, Motoyuki; Fujitani, Yoshio; Kawamori, Ryuzo; Watada, Hirotaka; Hirose, Takahisa

    2011-01-24

    Aims/Introduction:  The present study was designed to determine the effects of pioglitazone on glycemic control and atherosclerosis in patients with poorly controlled type 2 diabetes on insulin therapy.   The study was a prospective, randomized controlled trial involving 48 patients with inadequately controlled type 2 diabetes treated with insulin. We assigned patients to oral pioglitazone titrated from 15-30 mg (n = 22) or no pioglitazone (n = 26), to be taken in addition to their glucose-lowering drugs and other medications. Daily insulin doses and numbers were recorded during the study period.   The adjusted mean glycosylated hemoglobin (HbA1c) values decreased significantly by 1.13 ± 1.50% and 0.55 ± 0.76% in the pioglitazone and control groups, respectively. Significant decrease of HbA1c level was observed in the pioglitazone group compared with the control group (P < 0.05). The insulin dose lowered by 0.04 ± 0.10 units/kg/day in the pioglitazone group and increased by 0.03 ± 0.10 units/kg/day in the control group (P < 0.05). The number of insulin injections decreased by 0.1 ± 0.6 times/day in the pioglitazone group and increased by 0.2 ± 0.4 times/day in the control group (P < 0.05). The carotid intima-media thickness estimated by B-mode echography was carried out in both groups and decreased significantly at the end-point only in the pioglitazone group, relative to the baseline.   These findings show that pioglitazone is useful in improving glycemic control and preventing the progression of atherosclerosis in poorly-controlled type 2 diabetics on insulin therapy. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00064.x, 2010).

  11. Three-month treatment with pioglitazone reduces circulating C1q-binding adiponectin complex to total-adiponectin ratio, without changes in body mass index, in people with type 2 diabetes.

    Science.gov (United States)

    Nakatsuji, Hideaki; Kishida, Ken; Kobayashi, Hironori; Funahashi, Tohru; Shimomura, Iichiro

    2013-01-01

    We measured circulating C1q-binding adiponectin (C1q-APN) levels before and after 3-month treatment with pioglitazone in people with type 2 diabetes. The results indicate 3-month treatment with pioglitazone reduces circulating levels of C1q-APN/total-adiponectin ratio without changes in body mass index.

  12. Trans-illuminated laser speckle imaging of collateral artery blood flow in ischemic mouse hindlimb

    OpenAIRE

    Meisner, Joshua K.; Niu, Jacqueline; Sumer, Suna; Price, Richard J.

    2013-01-01

    Abstract. The mouse ischemic hindlimb model is used widely for studying collateral artery growth (i.e., arteriogenesis) in response to increased shear stress. Nonetheless, precise measurements of regional shear stress changes along individual collateral arteries are lacking. Our goal is to develop and verify trans-illumination laser speckle flowmetry (LSF) for this purpose. Studies of defibrinated bovine blood flow through tubes embedded in tissue-mimicking phantoms indicate that trans-illumi...

  13. Coronary collateral circulation in patients of coronary ectasia with significant coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Po-Chao Hsu

    Full Text Available OBJECTIVES: Patients with coronary ectasia (CE usually have coexisting coronary stenosis resulting in myoischemia. Coronary collateral plays an important role in protecting myocardium from ischemia and reducing cardiovascular events. However, limited studies investigate the role of CE in coronary collaterals development. METHODS: We evaluated 1020 consecutive patients undergoing coronary angiography and 552 patients with significant coronary artery disease (SCAD, defined as diameter stenosis more than 70%, were finally analyzed. CE is defined as the ectatic diameter 1.5 times larger than adjacent reference segment. Rentrop collateral score was used to classify patients into poor (grades 0 and 1 or good (grades 2 and 3 collateral group. RESULTS: 73 patients (13.2% had CE lesions which were most located in the right coronary artery (53.4%. Patients with CE had a lower incidence of diabetes (43.8% vs 30.1%, p = 0.03, higher body mass index (25.4±3.5 vs 26.7±4.6, p = 0.027 and poorer coronary collateral (58.2% vs 71.2%, p = 0.040. Patients with poor collateral (n = 331 had a higher incidence of CE (15.7% vs 9.5%, p = 0.040 and fewer diseased vessels numbers (1.96±0.84 vs 2.48±0.69, p<0.001. Multivariate analysis showed diabetes (odd ratio (OR 0.630, p = 0.026, CE (OR = 0.544, p = 0.048, and number of diseased vessels (OR = 2.488, p<0.001 were significant predictors of coronary collaterals development. CONCLUSION: The presence of CE was associated with poorer coronary collateral development in patients with SCAD.

  14. Posterior intercostal artery tortuosity and collateral branch points: a cadaveric study.

    Science.gov (United States)

    Shurtleff, E; Olinger, A

    2012-11-01

    Publications report observing tortuosity in the posterior intercostal arteries of elderly patients. Studies also describe the size and course of the collateral intercostal arteries. This information is clinically significant when performing thoracentesis and video-assisted thorascopic surgery. To the best of our knowledge, no studies have examined arterial tortuosity or described collateral artery origins relative to bony landmarks. The purpose of this study was to define a safe surgical zone for thoracic access using palpable external bony landmarks. A total of 348 intercostal spaces (3rd-8th) of 29 male and female embalmed cadavers were dissected from the vertebral body to the mid-axillary line to observe the posterior intercostal artery and its collateral branch. The origins of the collateral intercostal arteries relative to the midline of thoracic spinous processes were measured. Mild to moderate tortuosity (arterial curves covering 25- -50% of the intercostal space) was observed in at least one posterior intercostal artery in the majority of cadavers. The origins of the collateral intercostal arteries were variable relative to the midline. Additional collateral intercostal arteries distal to the primary collateral branch were observed, most commonly in the 5th intercostal space, which is used in video-assisted thorascopic surgery and thoracentesis. Tortuosity is common in the 3rd to the 8th posterior intercostal arteries, especially in individuals over the age of 60 years. Given the findings of this study, we recommend that any procedure involving placement of a surgical instrument into these intercostal spaces does so at least 120 mm lateral to the midline of the spinous processes. We also recommend pre-procedure ultrasound (intercostal scan) of the posterior and collateral intercostal arteries when performing non-emergent thoracentesis and video-assisted thorascopic surgery, particularly in patients over 60 years of age.

  15. Pioglitazone Upregulates Angiotensin Converting Enzyme 2 Expression in Insulin-Sensitive Tissues in Rats with High-Fat Diet-Induced Nonalcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2014-01-01

    Full Text Available Background and Aim. Thiazolidinediones (TZDs can improve hepatic steatosis in nonalcoholic steatohepatitis (NASH. Angiotensin (Ang II, the primary effector of renin-angiotensin system (RAS, plays vital roles in the development and progression of NASH. And some AngII-mediated effects can be regulated by TZDs. Angiotensin-converting enzyme (ACE 2, a new component of RAS, can degrade Ang II to attenuate its subsequent physiological actions. We aimed to evaluate the effects of TZDs on ACE2 expression in insulin-sensitive tissues in NASH rats. Methods. Forty rats were divided into the normal control, high-fat diet (HFD, pioglitazone control, and HFD plus pioglitazone groups. After 24 weeks of treatment, we evaluated changes in liver histology and tissue-specific ACE2 expression. Results. ACE2 gene and protein expression was significantly greater in liver and adipose tissue in the HFD group compared with normal control group, while was significantly reduced in skeletal muscle. Pioglitazone significantly reduced the degree of hepatic steatosis compared with the HFD group. Pioglitazone significantly increased ACE2 protein expression in liver, adipose tissue, and skeletal muscle compared with the HFD group. Conclusions. Pioglitazone improves hepatic steatosis in the rats with HFD-induced NASH and upregulates ACE2 expression in insulin-sensitive tissues.

  16. Leptin replacement improves postprandial glycemia and insulin sensitivity in human immunodeficiency virus-infected lipoatrophic men treated with pioglitazone: a pilot study.

    Science.gov (United States)

    Magkos, Faidon; Brennan, Aoife; Sweeney, Laura; Kang, Eun Seok; Doweiko, John; Karchmer, Adolf W; Mantzoros, Christos S

    2011-07-01

    Highly active antiretroviral therapy (HAART)-induced lipoatrophy is characterized by hypoleptinemia and insulin resistance. Evidence suggests that pioglitazone and recombinant methionyl human leptin (metreleptin) administration has beneficial effects in human immunodeficiency virus (HIV)-infected lipoatrophic patients. This proof-of-concept study aimed at evaluating whether the combination of metreleptin and pioglitazone has favorable effects, above and beyond pioglitazone alone, on both metabolic outcomes and peripheral lipoatrophy in HIV-infected patients on HAART. Nine HIV-positive men with at least 6 months of HAART exposure, clinical evidence of lipoatrophy, and low leptin concentrations (≤4 ng/mL) were placed on pioglitazone treatment (30 mg/d per os) and were randomized to receive either metreleptin (0.04 mg/kg subcutaneously once daily; n = 5) or placebo (n = 4) for 3 months in a double-blinded fashion. Compared with placebo, metreleptin reduced fasting serum insulin concentration, increased adiponectin concentration, reduced the homeostasis model assessment index of insulin resistance, and attenuated postprandial glycemia in response to a mixed meal (all P ≤ .02), but did not affect trunk and peripheral fat mass. HIV control was not affected, and no major adverse effects were observed. Metreleptin administration in HIV-positive, leptin-deficient patients with lipoatrophy treated with pioglitazone improves postprandial glycemia and insulin sensitivity. Results from this pilot study should be confirmed in larger clinical trials.

  17. Risk of cardiovascular disease and all-cause mortality among diabetic patients prescribed rosiglitazone or pioglitazone: a meta-analysis of retrospective cohort studies

    Institute of Scientific and Technical Information of China (English)

    CHEN Xin; YANG Li; ZHAI Suo-di

    2012-01-01

    Background The difference of cardiovascular effects between rosiglitazone and pioglitazone treatment for diabetic patients has not been thoroughly studied.We performed a meta-analysis to compare the risk of cardiovascular adverse effects in patients with type 2 diabetes treated with rosiglitazone compared to pioglitazone.Methods The Cochrane Library,PubMed,and Embase were searched to identify retrospective cohort studies assessing cardiovascular outcomes with rosiglitazone and pioglitazone.Meta-analysis of retrospective cohort studies was conducted using RevMan 5.0 software to calculate risk ratios.Results Of the 74 references identified,eight studies involving 945 286 patients fit the inclusion criteria for the analysis.The results of meta-analyses showed that,compared with pioglitazone,rosiglitazone therapy significantly increased the risk of myocardial infarction (risk ratios (RR) 1.17,95% confidence interval (CI) 1.04-1.32; P=0.01),the risk of heart failure (RR 1.18,95% CI 1.02-1.36; P=0.03),and total mortality (RR 1.13,95% CI 1.08-1.20; P <0.00001).Conclusion Compared with pioglitazone,rosiglitazone was associated with an increased risk of myocardial infarction,heart failure,and all-cause mortality in diabetic patients.

  18. Pioglitazone upregulates angiotensin converting enzyme 2 expression in insulin-sensitive tissues in rats with high-fat diet-induced nonalcoholic steatohepatitis.

    Science.gov (United States)

    Zhang, Wei; Xu, Yi-Zhi; Liu, Bo; Wu, Rong; Yang, Ying-Ying; Xiao, Xiao-Qiu; Zhang, Xia

    2014-01-01

    Thiazolidinediones (TZDs) can improve hepatic steatosis in nonalcoholic steatohepatitis (NASH). Angiotensin (Ang) II, the primary effector of renin-angiotensin system (RAS), plays vital roles in the development and progression of NASH. And some AngII-mediated effects can be regulated by TZDs. Angiotensin-converting enzyme (ACE) 2, a new component of RAS, can degrade Ang II to attenuate its subsequent physiological actions. We aimed to evaluate the effects of TZDs on ACE2 expression in insulin-sensitive tissues in NASH rats. Forty rats were divided into the normal control, high-fat diet (HFD), pioglitazone control, and HFD plus pioglitazone groups. After 24 weeks of treatment, we evaluated changes in liver histology and tissue-specific ACE2 expression. ACE2 gene and protein expression was significantly greater in liver and adipose tissue in the HFD group compared with normal control group, while was significantly reduced in skeletal muscle. Pioglitazone significantly reduced the degree of hepatic steatosis compared with the HFD group. Pioglitazone significantly increased ACE2 protein expression in liver, adipose tissue, and skeletal muscle compared with the HFD group. Pioglitazone improves hepatic steatosis in the rats with HFD-induced NASH and upregulates ACE2 expression in insulin-sensitive tissues.

  19. Genotype Phenotype Correlation of Genetic Polymorphism of PPAR Gamma Gene and Therapeutic Response to Pioglitazone in Type 2 Diabetes Mellitus- A Pilot Study

    Science.gov (United States)

    Sankaran, Ramalingam; Ramalingam, Sudha; Sairam, Thiagarajan; Somasundaram, LS

    2016-01-01

    Introduction Pro12Ala polymorphism is a missense mutation at codon 12 in peroxisome proliferator-activated receptor γ gene (PPARG). This polymorphism is known to be associated with increased insulin sensitivity. Pioglitazone, a thiazolidinedione, is an anti-diabetic drug which acts as an agonist at PPAR γ receptor. Aim To determine the association between Pro12Ala polymorphism of the PPARG and variation in therapeutic response to the PPARγ agonist, pioglitazone. Materials and Methods The study was done as a hospital based pilot project in 30 patients with type 2 diabetes mellitus, on treatment with sulfonylurea or metformin but without adequate glycaemic control. They were started on pioglitazone as add on therapy for a period of 12 weeks. The participants were categorized as responders and non-responders based on the change in HbA1C level after 12 weeks. Pro12Ala polymorphism was analysed by polymerase chain reaction-restriction fragment length polymorphism. Statistical Analysis Logistic regression analysis was done to evaluate the associations between age, baseline body weight, BMI, waist circumference, waist-hip ratio and Pro12Ala variants with the response to pioglitazone. The p-valuePro12Ala polymorphism and glycaemic response to pioglitazone. PMID:27042481

  20. Effects of long-term pioglitazone treatment on peripheral and central markers of aging.

    Directory of Open Access Journals (Sweden)

    Eric M Blalock

    Full Text Available BACKGROUND: Thiazolidinediones (TZDs activate peroxisome proliferator-activated receptor gamma (PPARgamma and are used clinically to help restore peripheral insulin sensitivity in Type 2 diabetes (T2DM. Interestingly, long-term treatment of mouse models of Alzheimer's disease (AD with TZDs also has been shown to reduce several well-established brain biomarkers of AD including inflammation, oxidative stress and Abeta accumulation. While TZD's actions in AD models help to elucidate the mechanisms underlying their potentially beneficial effects in AD patients, little is known about the functional consequences of TZDs in animal models of normal aging. Because aging is a common risk factor for both AD and T2DM, we investigated whether the TZD, pioglitazone could alter brain aging under non-pathological conditions. METHODS AND FINDINGS: We used the F344 rat model of aging, and monitored behavioral, electrophysiological, and molecular variables to assess the effects of pioglitazone (PIO-Actos(R a TZD on several peripheral (blood and liver and central (hippocampal biomarkers of aging. Starting at 3 months or 17 months of age, male rats were treated for 4-5 months with either a control or a PIO-containing diet (final dose approximately 2.3 mg/kg body weight/day. A significant reduction in the Ca(2+-dependent afterhyperpolarization was seen in the aged animals, with no significant change in long-term potentiation maintenance or learning and memory performance. Blood insulin levels were unchanged with age, but significantly reduced by PIO. Finally, a combination of microarray analyses on hippocampal tissue and serum-based multiplex cytokine assays revealed that age-dependent inflammatory increases were not reversed by PIO. CONCLUSIONS: While current research efforts continue to identify the underlying processes responsible for the progressive decline in cognitive function seen during normal aging, available medical treatments are still very limited

  1. Coronary collateral circulation:Effects on outcomes of acute anterior myocardial infarction after primary percutaneous coronary intervention

    Institute of Scientific and Technical Information of China (English)

    Bin Wang; Ya-Ling Han; Yi Li; Quan-Min Jing; Shou-Li Wang; Ying-Yan Ma; Geng Wang; Bo Luan; Xiao-Zeng Wang

    2011-01-01

    Background To investigate the effects of collateral coronary circulation on the outcome of the patients with anterior myocardial infarction (NII) with left anterior desending artery occlusion abruptly.Methods Data of 189 patients with acute anterior MI who had a primacy percutaneous coronary intervention (PCI) in the fast 12 h from the onset of symptoms between January 2004 and December 2008 were retrospective analyzed.Left anterior descending arteries (LAD) of all patients were occluded.LADs were reopened with primary PCL According to the collateral circulation,all patients were classified to two groups:no collateral group (n=111),patients without angiographic collateral filling of LAD or side branches (collateral index 0) and collateral group (n=78),and patients with angiographic collateral filling of LAD or side branches (collateral index 1,2 or 3).At one year's follow-up,the occurrence of death,reinfarction,stent thrombosis (ST),target vessel revascularization and readmission because of heart failure were observed.Results At one year,the mortality was lower in patients with collateral circulation compared with those without collateral circulation (1% vs.8%,P=0.049),whereas there were no differences in the occurrence of reinfarction,ST,target vessel revascularization and readmission because of heart failure.The occurrence of composite of endpoint was lower in patients with collateral circulation compared with those without collateral circulation (12% vs.26%; P=0.014).Conclusions Pre-exist collateral circulation may prefigure the satisfactory prognosis to the patients with acute anterior MI after primary PCI in the fast 12 h of MI onset.

  2. COLLATERAL'S IMPORTANCE IN SMES FINANCING: WHAT IS THE BANKS RESPONSE? SOME EVIDENCE FOR ROMANIA

    Directory of Open Access Journals (Sweden)

    Petria Nicolae

    2011-07-01

    Full Text Available Searching for funding, SMEs managers face various obstacles arising from information asymmetry, lack of experience, severe market conditions, and insufficient or unsatisfactory collaterals for banks (OECD 2006; Badulescu and Badulescu 2010; OECD 2000 and 2004; Lin and Sun 2006; Toivanen and Cresy, 2000. The collateral issue is extensively discussed in literature preventing moral hazard, the alignment the interests (Stiglitz and Weiss 1981:393-410; Chan and Thakor 1987:345-363; Jimenez and Saurina 2004, a means to discipline the borrowers behaviour (ex post given the existence of a credible threat (Aghion and Bolton 1992:473-494, or even banking behaviour on the market (Manove et al. 2001:726-744, Argentiero 2009. In the same time we find that the perception of firms, revealed by National Bank of Romania (NBR 2010 survey data, show that banks still use the collateral as a measure of pressure, in special in crisis times. For an important part of managers, the bank increased the level of required collateral for existing, renewing or new credits, asking for new covenants, revealing a paradox of crisis time: while the bank loans remained the favourite method of external financing needs of business, the banks often reduce their availability. Although the bank loan remains the favorite mean to support the growth ambitions, the higher level of collateral or lending costs are seen as principal obstacles by the majority of manager in EU. According to NBR survey, the influence of risk factors related to collateral had a climax at the end of 2008 and 2009, when the banks have tightened the requirement for loan guarantee. Using National Bank of Romania (NBR 2010 survey data, we show that the banks still use the collateral as a measure of pressure, in special in crisis times. For an important part of managers, the bank increased the level of required collateral for existing, renewing or new credits, asking for new covenants, revealing a paradox of crisis time

  3. Pharmacokinetics of pioglitazone, a thiazolidinedione derivative, in male Naeini (Iranian fat-tailed) sheep

    DEFF Research Database (Denmark)

    Ghoreishi, Sayed Mehdi; Rajaian, H.; Sheykhzade, Majid

    2012-01-01

    Pioglitazone (PGT) belongs to thiazolidinedione (TZD) family or insulin sensitizers that are potent ligands for peroxisome proliferator activated receptor gamma and are used in the treatment of type 2 diabetes mellitus. It has been shown that injection of TZD in cattle has some useful effects....../kg) was administered to five male sheep. Blood samples were collected at various time intervals, and PGT concentration was measured by a validated high-performance liquid chromatography method. The data obtained were best fitted into a two-compartment model for the IV route, and non-compartmental approach for oral...... route. The bioavailability of PGT was obtained to be approximately 62%. After IV injection of PGT, the elimination half-life (t 1/2ß), the volume of distribution at steady-state (V ss) and the elimination rate constant (k el) were obtained to be 4.04±0.88 h, 0.30±0.06 L/kg and 0.47±0.09 h-1...

  4. Pioglitazone for the treatment of type 2 diabetes in patients inadequately controlled on insulin

    Directory of Open Access Journals (Sweden)

    Stanley S Schwartz

    2010-07-01

    Full Text Available Stanley S SchwartzDiabetes Disease Management at the University of Pennsylvania, Penn Presbyterian Medical Center, Philadelphia Heart Institute, Philadelphia, Pennsylvania, USAAbstract: Insulin resistance and impaired beta-cell function are primary defects that occur early in the course of development of type 2 diabetes. Insulin resistance leads to hyperinsulinemia in order to maintain normal glucose tolerance. In most cases of type 2 diabetes, beta-cell dysfunction develops subsequent to the development of insulin resistance, and it is not until such beta-cell dysfunction develops that any abnormality in glucose tolerance is seen. Insulin resistance is a primary defect in type 2 diabetes. The risk of coronary heart disease is significantly increased in patients with type 2 diabetes. Cardiovascular disease causes 80% of all diabetic mortality, and in 75% of those cases, it is a result of coronary atherosclerosis. These points provide a rationale for early and aggressive management of cardiovascular risk in patients with diabetes. Thiazolidinediones represent an effective tool for targeting some features of this increased risk as they decrease insulin resistance and can prevent and/or delay diabetes progression.Keywords: pioglitazone, type 2 diabetes, insulin

  5. Pioglitazone, a Peroxisome Proliferator-Activated Receptor γ Agonist, Suppresses Rat Prostate Carcinogenesis

    Science.gov (United States)

    Suzuki, Shugo; Mori, Yukiko; Nagano, Aya; Naiki-Ito, Aya; Kato, Hiroyuki; Nagayasu, Yuko; Kobayashi, Mizuho; Kuno, Toshiya; Takahashi, Satoru

    2016-01-01

    Pioglitazone (PGZ), a peroxisome proliferator-activated receptor γ agonist, which is known as a type 2 diabetes drug, inhibits cell proliferation in various cancer cell lines, including prostate carcinomas. This study focused on the effect of PGZ on prostate carcinogenesis using a transgenic rat for an adenocarcinoma of prostate (TRAP) model. Adenocarcinoma lesions as a percentage of overall lesions in the ventral prostate were significantly reduced by PGZ treatment in a dose-dependent manner. The number of adenocarcinomas per given area in the ventral prostate was also significantly reduced by PGZ treatment. The Ki67 labeling index in the ventral prostate was also significantly reduced by PGZ. Decreased cyclin D1 expression in addition to the inactivation of both p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)κB were detected in PGZ-treated TRAP rat groups. In LNCaP, a human androgen-dependent prostate cancer cell line, PGZ also inhibited cyclin D1 expression and the activation of both p38 MAPK and NFκB. The suppression of cultured cell growth was mainly regulated by the NFκB pathway as detected using specific inhibitors in both LNCaP and PC3, a human androgen-independent prostate cancer cell line. These data suggest that PGZ possesses a chemopreventive potential for prostate cancer. PMID:27973395

  6. Effect of pioglitazone versus insulin glargine on cardiac size, function, and measures of fluid retention in patients with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Groop Leif

    2009-03-01

    Full Text Available Abstract Background Both insulin and thiazolidinediones (TZDs are effective in the treatment of hyperglycaemia and amelioration of insulin resistance in type 2 diabetes but have side effects including weight gain and fluid retention. The use of TZDs has been further hampered by the risk of adverse cardiovascular events including heart failure. The present study evaluated the effect of pioglitazone or insulin glargine on cardiac function and size as well as on surrogate markers of fluid retention such as weight, haemoglobin and natriuretic peptides. Methods Thirty patients with inadequate glycaemic control on metformin and sulfonylurea were randomised to receive add-on therapy with insulin glargine or pioglitazone for 26 weeks. Echocardiographic data and blood samples were collected from the two groups before the start of the treatment and after 26 weeks. Left ventricular end-diastolic and left atrial end-systolic volumes were quantified, weight measured and blood samples analyzed. Results After 26 weeks of treatment, the changes in HbA1c, weight and haemoglobin were similar between the two groups. HDL increased significantly in the pioglitazone group. While there was an increase in natriuretic peptides in the pioglitazone group (NT-proBNP 11.4 ± 19.6 to 22.8 ± 44.0, p = 0.046, the difference between the treatment groups was not significant. Left ventricular end-diastolic volume increased by 11% and left atrial end-systolic volume by 17% in the pioglitazone group (Both, p Conclusion This randomised pilot-study showed that six-month treatment with pioglitazone induced significant increases in natriuretic peptides and alterations of cardiac size. These changes were not observed with insulin glargine, which also is known to induce fluid retention. Larger randomised trials are warranted to confirm these findings.

  7. Protective effect of pioglitazone on cardiomyocyte apoptosis in low-dose streptozotocin & high-fat diet-induced type-2 diabetes in rats

    Directory of Open Access Journals (Sweden)

    Uma Bhandari

    2015-01-01

    Full Text Available Background & objectives: Cardiomyocyte apoptosis is one of the pathologic phenomena associated with diabetes and related conditions including obesity, insulin resistance and hyperlipidaemia. In the present study, the protective effects of pioglitazone on cardiomyocyte apoptosis was evaluated in experimental diabetes induced by low dose of streptozoticin (STZ combined with high fat diet (HFD in rats. Methods: Male Wistar rats (150-200 g were injected with low-dose STZ (45 mg/kg, i.v., single dose and orally fed with a HFD (20 g/day/rat for a period of 28 days and simultaneously treated with pioglitazone (20 mg/kg/p.o. for a period of 21 days (from 8 th day to 28 th day. On 29 th day blood was collected, serum separated and used for biochemical parameters. Heart tissue was used for cardiomyocyte apoptosis measurement and also for histopathological examination. Results: Pioglitazone treatment resulted in a decrease in cardiomyocyte apoptosis as revealed by a decrease in cardiac caspase-3, lactate dehydrogenase (LDH levels and DNA fragmentation, and an increase in Na+K+ATPase levels in diabetic rats. Cardiac histology of diabetic control rats showed dense focal fatty infiltration in the myocardial cells whereas normal architecture with regular morphology and well preserved cytoplasm was observed with pioglitazone treatment. Pioglitazone treatment significantly reduced the heart rate, mean arterial blood pressure, body mass index (BMI and levels of serum glucose, leptin, insulin, HOMA-IR, total cholesterol (TC and triglycerides (TGs, apoliproprotein-B glycosylated haemoglobin (HbA1c levels and atherogenic index, and increased the levels of serum high density lipoprotein cholesterol (HDL-C and cardiac antioxidant enzymes. Interpretation & conclusions: The present study results suggest that pioglitazone possesses cardiac anti-apoptotic potential in diabetic rat model and can be further explored for its use for treatment of diabetic cardiomyopathy.

  8. Pioglitazone-induced increase in the stearoyl-CoA desaturation index and fat accumulation in rat muscles are not related to lipoprotein lipase activity.

    Science.gov (United States)

    Ochiai, Masaru; Matsuo, Tatsuhiro

    2013-01-01

    Muscular insulin resistance is a characteristic of obesity and type 2 diabetes, but little is known about fatty acid (FA) metabolism in insulin-resistant skeletal muscle. In this study, we investigated the effects of the repeated administration of the PPAR-γ agonist pioglitazone on fat accumulation, FA composition, and stearoyl-CoA desaturase (SCD) index in rat tissues. Seventeen 4-week-old male Wistar rats were divided into control (C, n = 9) and pioglitazone treatment (P, n = 8) groups, and all the rats were fed a high-fat and high-sucrose diet for 8 weeks. Vehicle or pioglitazone (3 mg/kg) was orally administered daily to rats in the C group and P group, respectively. In the eighth week of the test period, an oral glucose tolerance test (OGTT) was performed after 12 h fasting. At the end of the test period, serum, liver, perirenal adipose tissue, and skeletal muscles were removed after 12 h fasting. The fasting serum and plasma glucose concentrations and OGTT glucose and insulin levels were significantly lower, while the serum adiponectin concentration was significantly higher in the P group than in the C group. Pioglitazone administration increased fat accumulation in the various muscle types examined, perirenal adipose tissue, and brown adipose tissue (BAT), but decreased fat accumulation in the liver. Pioglitazone administration increased the SCD indices for the muscles, perirenal adipose tissue, and liver, but not those of BAT. The lipoprotein lipase (LPL) activity of the BAT and perirenal adipose tissue, but not the muscles, was higher in the P group than in the C group. These results indicate that pioglitazone administration improved glucose tolerance and increased fat accumulation and SCD indices in the muscles and adipose tissues of rats. The increased fat accumulation was closely correlated with LPL activity in both adipose tissues, but not in the muscles.

  9. Genetic dissection of the Canq1 locus governing variation in extent of the collateral circulation.

    Directory of Open Access Journals (Sweden)

    Shiliang Wang

    Full Text Available BACKGROUND: Native (pre-existing collaterals are arteriole-to-arteriole anastomoses that interconnect adjacent arterial trees and serve as endogenous bypass vessels that limit tissue injury in ischemic stroke, myocardial infarction, coronary and peripheral artery disease. Their extent (number and diameter varies widely among mouse strains and healthy humans. We previously identified a major quantitative trait locus on chromosome 7 (Canq1, LOD = 29 responsible for 37% of the heritable variation in collateral extent between C57BL/6 and BALB/c mice. We sought to identify candidate genes in Canq1 responsible for collateral variation in the cerebral pial circulation, a tissue whose strain-dependent variation is shared by similar variation in other tissues. METHODS AND FINDINGS: Collateral extent was intermediate in a recombinant inbred line that splits Canq1 between the C57BL/6 and BALB/c strains. Phenotyping and SNP-mapping of an expanded panel of twenty-one informative inbred strains narrowed the Canq1 locus, and genome-wide linkage analysis of a SWRxSJL-F2 cross confirmed its haplotype structure. Collateral extent, infarct volume after cerebral artery occlusion, bleeding time, and re-bleeding time did not differ in knockout mice for two vascular-related genes located in Canq1, IL4ra and Itgal. Transcript abundance of 6 out of 116 genes within the 95% confidence interval of Canq1 were differentially expressed >2-fold (p-value<0.05÷150 in the cortical pia mater from C57BL/6 and BALB/c embryos at E14.5, E16.5 and E18.5 time-points that span the period of collateral formation. CONCLUSIONS: These findings refine the Canq1 locus and identify several genes as high-priority candidates important in specifying native collateral formation and its wide variation.

  10. Morphology of the medial collateral ligament of the knee

    Directory of Open Access Journals (Sweden)

    Gill Thomas J

    2010-09-01

    Full Text Available Abstract Background Quantitative knowledge on the anatomy of the medial collateral ligament (MCL is important for treatment of MCL injury and for MCL release during total knee arthroplasty (TKA. The objective of this study was to quantitatively determine the morphology of the MCL of human knees. Methods 10 cadaveric human knees were dissected to investigate the MCL anatomy. The specimens were fixed in full extension and this position was maintained during the dissection and morphometric measurements. The outlines of the insertion sites of the superficial MCL (sMCL and deep MCL (dMCL were digitized using a 3D digitizing system. Results The insertion areas of the superficial MCL (sMCL were 348.6 ± 42.8 mm2 and 79.7 ± 17.6 mm2 on the tibia and femur, respectively. The insertion areas of the deep MCL (dMCL were 63.6 ± 13.4 mm2 and 71.9 ± 14.8 mm2 on the tibia and femur, respectively. The distances from the centroids of the tibial and femoral insertions of the sMCL to the tibial and femoral joint line were 62.4 ± 5.5 mm and 31.1 ± 4.6 mm, respectively. The distances from the centroids of dMCL in the tibial insertion and the femoral insertion to the tibial and femoral joint line were 6.5 ± 1.3 mm and 20.5 ± 4.2 mm, respectively. The distal portion of the dMCL (meniscotibial ligament - MTL was approximately 1.7 times wider than the proximal portion of the dMCL (meniscofemoral ligament - MFL, whereas the MFL was approximately 3 times longer than the MTL. Conclusions The morphologic data on the MCL may provide useful information for improving treatments of MCL-related pathology and performing MCL release during TKA.

  11. A cost-effectiveness analysis of pioglitazone plus metformin compared with rosiglitazone plus metformin from a third-party payer perspective in the US.

    Science.gov (United States)

    St Charles, Meaghan; Minshall, Michael E; Pandya, Bhavik J; Baran, Robert W; Tunis, Sandra L

    2009-06-01

    The long-term cost-effectiveness of using pioglitazone plus metformin (Actoplusmet dagger) compared with rosiglitazone plus metformin (Avandamet double dagger) in treating type 2 diabetes (T2DM) was assessed from a US third-party payer perspective. Clinical efficacy (change in HbA(1c) and lipids) and baseline cohort parameters were extracted from a 12-month, randomized clinical trial (Derosa et al., 2006) evaluating the efficacy and tolerability of pioglitazone versus rosiglitazone, both in addition to metformin, in adult T2DM patients with insufficient glucose control (n = 96). A Markov-based model was used to project clinical and economic outcomes over 35 years, discounted at 3% per annum. Costs for complications were taken from published sources. Base-case assumptions were assessed through several sensitivity analyses. Outcomes included incremental life-years, quality-adjusted life-years (QALYs), total direct medical costs, cumulative incidence of complications and associated costs, and incremental cost-effectiveness ratios (ICERs). Compared to rosiglitazone plus metformin, pioglitazone plus metformin was projected to result in a modest improvement in 0.187 quality-adjusted life-years. Over patients' lifetimes, total direct medical costs were projected to be marginally lower with pioglitazone plus metformin (difference -$526.), largely due to reduced CVD complication costs. While costs were higher among renal, ulcer/amputation/neuropathy, and eye complications in the pioglitazone plus metformin group, the cost savings for CVD complications outweighed their economic impact. Pioglitazone plus metformin was found to be a dominant long-term treatment strategy in the US compared to rosiglitazone plus metformin. Sensitivity analyses showed findings to be robust under almost all scenarios, including short-term time horizons, 6% discounting, removal of individual lipid parameters, and modifications of patient cohort to more closely represent a US T2DM population

  12. Analysis of Case Reports of Pioglitazone's Adverse Drug Reaction%吡格列酮的不良反应病例报告分析

    Institute of Scientific and Technical Information of China (English)

    曾艳; 李晓玲; 王育琴

    2011-01-01

    Objective:To review and analyze the case reports of pioglitazone' s adverse drug reactions to provide reference for rational and safe use of pioglitazone. Method: Reactions Weekly was searched for case reports with the key word ' pioglitazone' , types of ADRs of the case reports were classified and the patients' clinical characteristics, types and outcome of ADRs were analyzed. Result:41 case reports of ADRs associated with pioglitazone were found. 41 patients consisted of 21 males, 19 females and 1 unidentified, and were aged 30 -82 years with a pioglitazone' s dosage 15 -45 mg per day and its duration from 1 week to 2 years. Their ADRs were involved in many systems such as cardiovascular system, respiratory system and biliary system. Except for 1 patient with unaquired outcome, 8 patients died, the rest recovered after pioglitazone' s discontinuation with or without therapy. Conclusion: Pioglitazone could induce severe adverse reactions such as heart failure and liver failure. The medical staff should monitor ADR as they used piolitazone.%目的:对吡格列酮药品不良反应(ADR)病例报告进行回顾分析,为临床合理安全使用提供参考.方法:以"pioglitazone"为检索词检索Reactions Weekly,将检索到的ADR病例报告分类,分别提取患者的临床特征及ADR类型、转归等信息,进行统计分析.结果:检索到与吡格列酮相关ADR病例报告41份.41名患者中男21例,女19例,1名性别不明.年龄30-82岁,吡格列酮剂量15-45 mg·d-1,疗程1周-2年.发生ADR分别涉及心血管系统、呼吸系统、肝胆系统等多个系统/器官.41名患者中1名转归不明,8名死亡,其余患者停药后或停药经治疗后好转或痊愈.结论:吡格列酮引起的心衰、肝衰竭等ADR会给患者带来较大危害,甚至危及到生命.医务人员在使用吡格列酮的同时,要关注其ADR.

  13. The peroxisome proliferator-activated receptor γ agonist pioglitazone preserves bone microarchitecture in experimental arthritis by reducing the interleukin-17-dependent osteoclastogenic pathway.

    Science.gov (United States)

    Koufany, Meriem; Chappard, Daniel; Netter, Patrick; Bastien, Claire; Weryha, Georges; Jouzeau, Jean-Yves; Moulin, David

    2013-12-01

    To investigate the effect of pioglitazone on inflammation-induced bone loss and changes in bone microarchitecture in rats with adjuvant-induced arthritis (AIA), focusing on the contribution of interleukin-17 (IL-17) and the balance of RANKL and osteoprotegerin (OPG). Male Lewis rats sensitized with Freund's complete adjuvant were treated orally for 21 days with 30 mg/kg/day of pioglitazone or vehicle. Arthritis severity was evaluated by clinical and histologic examination. Bone mineral density (BMD) was assessed by dual x-ray absorptiometry. The therapeutic effect of pioglitazone on changes of the bone architecture was determined by micro-computed tomography (micro-CT). Levels of RANKL, OPG, and IL-17 were determined by serum immunoassay and by synovial tissue immunohistochemistry. Messenger RNA for IL-17 and retinoic acid receptor-related orphan nuclear receptor γt (RORγt) was evaluated by quantitative reverse transcription-polymerase chain reaction and IL-17 promoter activity by gene-reporter assay. Micro-CT analysis revealed that pioglitazone treatment reduced arthritis severity and bone erosion scores and increased BMD in comparison to vehicle treatment. Cortical bone thickness was preserved, although the major beneficial effect of pioglitazone was on indices of the trabeculae, especially trabecular separation. Pioglitazone reduced the ratio of RANKL to OPG, in both the serum and the inflamed synovium. Circulating levels of IL-17 were significantly reduced by pioglitazone treatment, as were the percentages of IL-17-positive cells, mainly polymorphonuclear cells, in the inflamed synovium. Induction of IL-17 was strictly dependent on the binding of RORγt to IL-17 promoter, and lentiviral overexpression of peroxisome proliferator-activated receptor γ (PPARγ) reduced the expression of RORγt. Pioglitazone decreased the level of inflammatory bone destruction and protected the bone microarchitecture in rats with AIA by controlling the circulating and local

  14. STUDY ON ESSENCE OF CHANNEL AND COLLATERAL COURSES%经络路线的实质研究

    Institute of Scientific and Technical Information of China (English)

    谢浩然

    2007-01-01

    @@ The channels and collateral courses are longitudinal and horizontal passages of liquid and gas between fascia along channels and collaterals,their forms are band-shaped lines of natural winding with different thicknesses,which are approximate to the classical connective lines between the classical channels and collaterals and aeupoints (il lustrated lines),and similar to the lines of needling response propagating along channels and band-shaped lines of isotope tracing along channels.The followings are about studies on structures,channel-qi,the pathway of qi,regulation and essence of channel and collateral courses.

  15. Pioglitazone ameliorates nonalcoholic steatohepatitis by down-regulating hepatic nuclear factor-kappa B and cyclooxygenases-2 expression in rats

    Institute of Scientific and Technical Information of China (English)

    ZHAO Jia-sheng; ZHU Feng-shang; LIU Su; YANG Chang-qing; CHEN Xi-mei

    2012-01-01

    Background Pioglitazone is effective in nonalcoholic steatohepatitis (NASH),but the mechanisms of action are not completely understood.This study was designed to investigate the effects of pioglitazone on hepatic nuclear factor-kappa B (NF-κB) and cyclooxygenases-2 (COX-2) expression in NASH rats.Methods Thirty Sprague-Dawley male rats were randomly assigned to a control group (n=10),NASH group (n=10),and pioglitazone treatment group (n=10).Liver tissues were processed for histology by hematoxylin & eosin and Masson stained.Serum alanine aminotransferase (ALT),cholesterol,triglyceride,fasting blood glucose (FBG),fasting insulin (FINS) levels and biochemical parameters of antioxidant enzyme activities,tumor necrosis factor alpha (TNF-α),prostaglandin E2 (PGE2) levels in serum and liver were measured.The mRNA and protein expression of peroxisome proliferator-activated receptor gamma (PPARy),NF-κB and COX-2 were determined by real-time polymerase chain reaction,Westem blotting and immunohistochemistry.One-way analysis of variance (ANOVA) and Wilcoxon's signed-rank test was used for the statistical analysis.Results There were severe steatosis,moderate inflammatory cellular infiltration and fibrosis in NASH rats.After pioglitazone treatment,steatosis,inflammation and fibrosis were significantly improved compared with the NASH group(X2=20.40,P <0.001; )X2=20.17,P <0.001; X2=13.98,P=0.002).Serum ALT,cholesterol,triglyceride,FBG,FINS levelswere significantly elevated in the NASH group (P <0.05).In the NASH group,total anti-oxidation competence (T-AOC),superoxide dismutase (SOD),catalase (CAT),glutathione peroxidase (GSH-PX) and malondialdehyde (MDA) levels inserum and liver were conspicuous disordered than those parameters in the control group.Meanwhile,TNF-α and PGE2levels in serum and liver were significantly increased compared with the control group.Immunohistochemistry showedNF-KB and COX-2 expression in liver was significantly elevated.However,PPARy level

  16. Impact of alogliptin and pioglitazone on lipid metabolism in islets of prediabetic and diabetic Zucker Diabetic Fatty rats.

    Science.gov (United States)

    Cai, Ying; Lydic, Todd A; Turkette, Thomas; Reid, Gavin E; Olson, L Karl

    2015-05-01

    Prolonged exposure of pancreatic beta (β) cells to elevated glucose and free fatty acids (FFA) as occurs in type 2 diabetes results in loss of β cell function and survival. In Zucker Diabetic Fatty (ZDF) rats, β cell failure is associated with increased triacylglyceride (TAG) synthesis and disruption of the glycerolipid/FFA (GL/FFA) cycle, a critical arm of glucose-stimulated insulin secretion (GSIS). The aim of this study was to determine the impact of activation of PPARγ and increased incretin action via dipeptidyl-peptidase inhibition using pioglitazone and/or alogliptin, respectively, on islet lipid metabolism in prediabetic and diabetic ZDF rats. Transition of control prediabetic ZDF rats to diabetes was associated with reduced plasma insulin levels, reduced islet insulin content and GSIS, reduced stearoyl-CoA desaturase 2 (SCD 2) expression, and increased islet TAG, diacylglyceride (DAG) and ceramides species containing saturated FA. Treatment of prediabetic ZDF rats with a combination of pioglitazone and alogliptin, but not individually, prevented the transition to diabetes and was associated with marked lowering of islet TAG and DAG levels. Pioglitazone and alogliptin, however, did not restore SCD2 expression, the degree of FA saturation in TAG, DAG or ceramides, islet insulin content, or lower ceramide levels. These findings are consistent with activation of PPARγ and increased incretin action working in concert to restore GL/FFA cycle in β cells of ZDF rats. Restoration of the GL/FFA cycle without correcting islet FA desaturation, production of islet ceramides, and/or insulin sensitivity, however, may place these islets at risk for β cell failure.

  17. Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on background metformin and pioglitazone

    OpenAIRE

    Forst, T; Guthrie, R.; Goldenberg, R; Yee, J.; Vijapurkar, U; Meininger, G; Stein, P.

    2014-01-01

    Aim The efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, was evaluated in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and pioglitazone. Methods In this randomized, double-blind, phase 3 study, patients (N = 342) received canagliflozin 100 or 300 mg during a 26-week, placebo-controlled, core period and a 26-week, active-controlled extension in which placebo-treated patients were switched to sitagliptin 100 mg. Efficacy ...

  18. Trans-illuminated laser speckle imaging of collateral artery blood flow in ischemic mouse hindlimb.

    Science.gov (United States)

    Meisner, Joshua K; Niu, Jacqueline; Sumer, Suna; Price, Richard J

    2013-09-01

    The mouse ischemic hindlimb model is used widely for studying collateral artery growth (i.e., arteriogenesis) in response to increased shear stress. Nonetheless, precise measurements of regional shear stress changes along individual collateral arteries are lacking. Our goal is to develop and verify trans-illumination laser speckle flowmetry (LSF) for this purpose. Studies of defibrinated bovine blood flow through tubes embedded in tissue-mimicking phantoms indicate that trans-illumination LSF better maintains sensitivity with an increasing tissue depth when compared to epi-illumination, with an ∼50% reduction in the exponential decay of the speckle velocity signal. Applying trans-illuminated LSF to the gracilis muscle collateral artery network in vivo yields both improved sensitivity and reduced noise when compared to epi-illumination. Trans-illuminated LSF images reveal regional differences in collateral artery blood velocity after femoral artery ligation and are used to measure an ∼2-fold increase in the shear stress at the entrance regions to the muscle. We believe these represent the first direct measurements of regional shear stress changes in individual mouse collateral arteries. The ability to capture deeper vascular signals using a trans-illumination configuration for LSF may expand the current applications for LSF, which could have bearing on determining how shear stress magnitude and direction regulate arteriogenesis.

  19. Increased circulating monocyte count is related to good collateral development in coronary artery disease.

    Science.gov (United States)

    Kocaman, Sinan Altan; Arslan, Uğur; Tavil, Yusuf; Okuyan, Hizir; Abaci, Adnan; Cengel, Atiye

    2008-04-01

    Monocytes have been shown to take an important role in collateral growth in animal studies. The aim of the study was to investigate the relation of circulating monocyte count with collateral development in patients with severely stenotic CAD. Patients who had > or =95% stenosis in at least one major coronary artery were included in the study. Coronary angiograms of 210 eligible patients from our database were analyzed again and 103 of them had good and 107 had poor collateral development according to Cohen-Rentrop method. Only the monocyte count was found to be significantly different between two groups (671+/-218 mm(-3) versus 522+/-195 mm(-3), p<0.001) when multivariate analysis was performed and an increased monocyte count was observed in the good collateral group (Odds ration [OR], 2.918; 95% confidence interval [CI], 1.281-6.648, p=0.011). This study in which the relationship between monocyte count in blood and collateral development was disclosed has a potential importance in clinical and basic cardiovascular medicine.

  20. Prevention of the collapse of pial collaterals by remote ischemic perconditioning during acute ischemic stroke.

    Science.gov (United States)

    Ma, Junqiang; Ma, Yonglie; Dong, Bin; Bandet, Mischa V; Shuaib, Ashfaq; Winship, Ian R

    2017-08-01

    Collateral circulation is a key variable determining prognosis and response to recanalization therapy during acute ischemic stroke. Remote ischemic perconditioning (RIPerC) involves inducing peripheral ischemia (typically in the limbs) during stroke and may reduce perfusion deficits and brain damage due to cerebral ischemia. In this study, we directly investigated pial collateral flow augmentation due to RIPerC during distal middle cerebral artery occlusion (MCAo) in rats. Blood flow through pial collaterals between the anterior cerebral artery (ACA) and the MCA was assessed in male Sprague Dawley rats using in vivo laser speckle contrast imaging (LSCI) and two photon laser scanning microscopy (TPLSM) during distal MCAo. LSCI and TPLSM revealed that RIPerC augmented collateral flow into distal MCA segments. Notably, while control rats exhibited an initial dilation followed by a progressive narrowing of pial arterioles 60 to 150-min post-MCAo (constricting to 80-90% of post-MCAo peak diameter), this constriction was prevented or reversed by RIPerC (such that vessel diameters increased to 105-110% of post-MCAo, pre-RIPerC diameter). RIPerC significantly reduced early ischemic damage measured 6 h after stroke onset. Thus, prevention of collateral collapse via RIPerC is neuroprotective and may facilitate other protective or recanalization therapies by improving blood flow in penumbral tissue.

  1. Development of collateral vessels: A new paradigm in CAM angiogenesis model.

    Science.gov (United States)

    Gatne, Dipti P; Mungekar, Snehal; Addepalli, Veeranjaneyulu; Mohanraj, Krishnapriya; Ghone, Sanjeevani A; Rege, Nirmala N

    2016-01-01

    The chorioallantoic membrane (CAM) assay is one of the most widely used models to study angiogenesis. In this study, collateral vessel development is reported in CAM assay useful in analysis of angiogenesis. Four days old white Leghorn fertilized chicken eggs were inoculated with vehicle, standard or test angiogenesis inhibitor using standard protocol. Central vessel growth was seen tapering down and collateral vessels were developed from the lower side of the chorioallantoic membrane moving upward in 12 days old standard or test treated CAMs. In the absence of the central vessel, collateral blood supply helped in survival of embryos. Hence, development of collateral vessels was used for ranking of blood vessels and angiogenesis in addition to well-known standard parameters related to central vessel. The finding could differentiate molecules inhibiting angiogenesis with or without collateralization which is crucial in anti-angiogenic therapy used for cardiovascular diseases and cancer. This study proposes a new avenue to distinguish pro-angiogenic molecules from anti-angiogenic ones as well as anti-angiogenic molecules which may or may not support alternative vascularization pathway that would have great impact on future angiogenic and anti-angiogenic therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. The role of VEGF and KDR polymorphisms in moyamoya disease and collateral revascularization.

    Directory of Open Access Journals (Sweden)

    Young Seok Park

    Full Text Available We conducted a case-control study to investigate whether vascular endothelial growth factor (VEGF -2578, -1154, -634, and 936 and kinase insert domain containing receptor (KDR -604, 1192, and 1719 polymorphisms are associated with moyamoya disease. Korean patients with moyamoya disease (n = 107, mean age, 20.9±15.9 years; 66.4% female and 243 healthy control subjects (mean age, 23.0±16.1 years; 56.8% female were included. The subjects were divided into pediatric and adult groups. Among the 64 surgical patients, we evaluated collateral vessel formation after 2 years and divided patients into good (collateral grade A or poor (collateral grade B and C groups. The frequencies and distributions of four VEGF (-2578, -1154, -634, and 936 and KDR (-604, 1192, and 1719 polymorphisms were assessed from patients with moyamoya disease and compared to the control group. No differences were observed in VEGF -2578, -1154, -634, and 936 or KDR -604, 1192, and 1719 polymorphisms between the control group and moyamoya disease group. However, we found the -634CC genotype occurred less frequently in the pediatric moyamoya group (p = 0.040 whereas the KDR -604C/1192A/1719T haplotype increased the risk of pediatric moyamoya (p = 0.024. Patients with the CC genotype of VEGF -634 had better collateral vessel formation after surgery. Our results suggest that the VEGF -634G allele is associated with pediatric moyamoya disease and poor collateral vessel formation.

  3. Treatment of Ulnar Collateral Ligament Tears of the Elbow

    Science.gov (United States)

    Erickson, Brandon J.; Bach, Bernard R.; Verma, Nikhil N.; Bush-Joseph, Charles A.; Romeo, Anthony A.

    2017-01-01

    Background: Ulnar collateral ligament (UCL) tears have become common, and UCL reconstruction (UCLR) is currently the preferred surgical treatment method for treating UCL tears. Purpose/Hypothesis: The purpose of this study was to review the literature surrounding UCL repair and determine the viability of new repair techniques for treatment of UCL tears. We hypothesized that UCL repair techniques will provide comparable results to UCLR for treatment of UCL tears. Study Design: Systematic review and meta-analysis; Level of evidence, 4. Methods: A systematic review was registered with PROSPERO and performed with PRISMA guidelines using 3 publicly available free databases. Biomechanical and clinical outcome investigations reporting on UCL repair with levels of evidence 1 through 4 were eligible for inclusion. Descriptive statistics were calculated for each study and parameter/variable analyzed. Results: Of the 46 studies eligible, 4 studies (3 clinical and 1 biomechanical) were included. There were 92 patients (n = 92 elbows; 61 males [62.3%]; mean age, 21.9 ± 4.7 years) included in the clinical studies, with a mean follow-up of 49 ± 14.4 months. Eighty-six percent of repairs performed were on the dominant elbow, and 38% were in college athletes. Most UCL repairs (66.3%) were performed via suture anchors. After UCL repair, 87.0% of patients were able to return to sport. Overall, 94.9% of patients scored excellent/good on the Andrews-Carson score. Patients who were able to return to sport after UCL repair did so within 6 months after surgery. Biomechanically, when UCL repair was compared with the modified Jobe technique, the repair group showed significantly less gap formation than the reconstruction group. Conclusion: In patients for whom repair is properly indicated, UCL repair provides similar return-to-sport rates and clinical outcomes with shorter return-to-sport timing after repair compared with UCL reconstruction. Future outcome studies evaluating UCL repair

  4. SmPL: A Domain-Specific Language for Specifying Collateral Evolutions in Linux Device Drivers

    DEFF Research Database (Denmark)

    Padioleau, Yoann; Lawall, Julia Laetitia; Muller, Gilles

    2007-01-01

    identifying the affected files and modifying all of the code fragments in these files that in some way depend on the changed interface. We have studied the collateral evolution problem in the context of Linux device drivers. Currently, collateral evolutions in Linux are mostly done manually using a text...... editor, possibly with the help of tools such as grep. The large number of Linux drivers, however, implies that this approach is time-consuming and unreliable, leading to subtle errors when modifications are not done consistently. In this paper, we propose a transformation language, SmPL, to specify...... collateral evolutions. Because Linux programmers are accustomed to exchanging, reading, and manipulating program modifications in terms of patches, we build our language around the idea and syntax of a patch, extending patches to semantic patches. Udgivelsesdato: January 3...

  5. Effect of polymers and media type on extending the dissolution of amorphous pioglitazone and inhibiting the recrystallization from a supersaturated state.

    Science.gov (United States)

    Shi, Nian-Qiu; Yao, Jing; Wang, Xing-Lin

    2014-08-01

    Amorphous forms of crystalline drug are widely utilized for bioavailability enhancement of low solubility drugs in the pharmaceutical industry. Polymers have been found to be effective crystallization inhibitors for amorphous forms in solid states during storage or in liquid states during dissolution process. The dissolution and crystallization behaviors of these amorphous forms in the presence or absence of polymers are still far from adequately understood especially in different dissolution environments. The objective of this study was to investigate the effects of polymers and media type on extending the dissolution of amorphous pioglitazone and inhibiting the recrystallization from a supersaturated state. Polyvinylpyrrolidone K30 (PVPK30), polyvinylpyrrolidone K90 (PVPK90), polyethylene glycol 6000 (PEG6000), polyethylene-polypropylene glycol 188 (F-68), hydroxypropylmethylcellulose (HPMC) and beta-cyclodextrin (β-CD) were employed to understand these behaviors changes because these polymers were used widely. Three solutions including neutral water and phosphate buffer solutions (PBS, pH6.8 and pH7.4) were adopted as dissolution media to determine the behaviors changes comprehensively. In the presence of polymers, dissolution and solubility were extended to different degrees in three media. Polymers can delay the crystallization routes dependently of the medium type. Buffer salts in media reduced the dissolution and accelerated the crystallization process. Crystallization inhibition of these polymers was strongly dependent on the type and pH of media. HPMC displayed the strongest crystallization inhibition effects, resulting in the greatest degree of maintaining a supersaturated state that can sustain most effectively for biologically relevant timeframes.

  6. Pioglitazone, an anti-diabetic drug requires sustained MAPK activation for its anti-tumor activity in MCF7 breast cancer cells, independent of PPAR-γ pathway.

    Science.gov (United States)

    Kole, Labanyamoy; Sarkar, Mrinmoy; Deb, Anwesha; Giri, Biplab

    2016-02-01

    The thiazolidinedione (TZD) class of peroxisome proliferator-activated receptor gamma (PPAR-γ) ligands are known for their ability to induce adipocyte differentiation, to increase insulin sensitivity including anticancer properties. But, whether or not upstream events like MAPK activation or PPAR-γ signaling are involved or associated with this anticancer activity is not well understood in breast cancer cells. The role of MAPK and PPAR pathways during the pioglitazone (Pio) induced PPAR-γ independent anticancer activity in MCF7 cells has been focused here. The anticancer activity of Pio has been investigated in breast cancer cells in vitro. Anti-tumor effects were assessed by alamar blue assay, Western blot analysis, cell cycle analysis, and annexin V-FITC/PI binding assay by flow cytometry, Hoechst staining and luciferase assay. The anticancer activity of Pio is found to be correlating with the up regulation of CDKIs (p21/p27) and down regulation of CDK-4. This study demonstrates that the induction of CDKIs by Pio is due to the sustained activation of MAPK. The Pio-mediated activation of MAPK is transmitted to activate ELK-1 and the related anti-proliferation is blocked by MEK inhibitor (PD-184352). Pio suppresses the proliferation of MCF7 cells, at least partly by a PPAR-γ-independent mechanism involving the induction of p21 which in turn requires sustained activation of MAPK. These findings implicate the utility of Pio in the treatment of PPAR positive or negative human cancers and the development of a new class of compounds to enhance the effectiveness of Pio. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  7. Subcellular structural plasticity caused by the absence of the fast Ca2+ buffer calbindin D-28k in recurrent collaterals of cerebellar Purkinje neurons

    Directory of Open Access Journals (Sweden)

    David eOrduz

    2014-11-01

    Full Text Available Purkinje cells (PC control spike timing of neighboring PC by their recurrent axon collaterals. These synapses underlie fast cerebellar oscillations and are characterized by a strong facilitation within a time window of <20 ms during paired-pulse protocols. PC express high levels of the fast Ca2+ buffer protein calbindin D-28k (CB. As expected from the absence of a fast Ca2+ buffer, presynaptic action potential-evoked [Ca2+]i transients were previously shown to be bigger in PC boutons of young (second postnatal week CB-/- mice, yet IPSC mean amplitudes remained unaltered in connected CB-/- PC. Since PC spine morphology is altered in adult CB-/- mice (longer necks, larger spine head volume, we summoned that morphological compensation/adaptation mechanisms might also be induced in CB-/- PC axon collaterals including boutons. In these mice, biocytin-filled PC reconstructions revealed that the number of axonal varicosities per PC axon collateral was augmented, mostly confined to the granule cell layer. Additionally, the volume of individual boutons was increased, evidenced from z-stacks of confocal images. EM analysis of PC-PC synapses revealed an enhancement in active zone (AZ length by approximately 23%, paralleled by a higher number of docked vesicles per AZ in CB-/- boutons. Moreover, synaptic cleft width was larger in CB-/- (23.8 ± 0.43 nm compared to wild type (21.17 ± 0.39 nm synapses. We propose that the morphological changes, i.e. the larger bouton volume, the enhanced AZ length and the higher number of docked vesicles, in combination with the increase in synaptic cleft width likely modifies the GABA release properties at this synapse in CB-/- mice. We view these changes as adaptation/homeostatic mechanisms to likely maintain (preserve characteristics of synaptic transmission in the absence of the fast Ca2+ buffer CB. Our study provides further evidence on the functioning of the Ca2+ homeostasome.

  8. Extrahepatic collaterals and liver damage in embolotherapy for ruptured hepatic artery pseudoaneurysm following hepatobiliary pancreatic surgery

    Institute of Scientific and Technical Information of China (English)

    Yoshitsugu Tajima; Tamotsu Kuroki; Ryuji Tsutsumi; Ichiro Sakamoto; Masataka Uetani; Takashi Kanematsu

    2007-01-01

    AIM: To evaluate the effects of extrahepatic collaterals to the liver on liver damage and patient outcome after embolotherapy for the ruptured hepatic artery pseudoaneurysm following hepatobiliary pancreatic surgery.METHODS: We reviewed 9 patients who underwent transcatheter arterial embolization (TAE) for the ruptured hepatic artery pseudoaneurysm following major hepatobiliary pancreatic surgery between June 1992 and April 206. We paid special attention to the extrahepatic arterial collaterals to the liver which may affect post-TAE liver damage and patient outcome.RESULTS: The underlying diseases were all malignancies, and the surgical procedures included hepatopancreatoduodenectomy in 2 patients, hepatic resection with removal of the bile duct in 5, and pancreaticoduodenectomy in 2. A total of 11 pseudoaneurysm developed: 4in the common hepatic artery, 4 in the proper hepatic artery, and 3 in the right hepatic artery. Successful hemostasis was accomplished with the initial TAE in all patients, except for 1. Extrahepatic arterial pathways to the liver, including the right inferior phrenic artery, the jejunal branches, and the aberrant left hepatic artery,were identified in 8 of the 9 patients after the completion of TAE. The development of collaterals depended on the extent of liver mobilization during the hepatic resection,the postoperative period, the presence or absence of an aberrant left hepatic artery, and the concomitant arterial stenosis adjacent to the pseudoaneurysm. The liver tolerated TAE without significant consequences when at least one of the collaterals from the inferior phrenic artery or the aberrant left hepatic artery was present. One patient, however, with no extrahepatic collaterals died of liver failure due to total liver necrosis 9 d after TAE.CONCLUSION: When TAE is performed on ruptured hepatic artery pseudoaneurysm, reduced collateral pathways to the liver created by the primary surgical procedure and a short postoperative interval may

  9. Comparative effects of pioglitazone and rosiglitazone on plasma levels of soluble receptor for advanced glycation end products in type 2 diabetes mellitus patients.

    Science.gov (United States)

    Oz Gul, Ozen; Tuncel, Ercan; Yilmaz, Yusuf; Ulukaya, Engin; Gul, Cuma Bulent; Kiyici, Sinem; Oral, Arzu Yilmaztepe; Guclu, Metin; Ersoy, Canan; Imamoglu, Sazi

    2010-01-01

    Low levels of soluble receptor for advanced glycation end products (sRAGE) have been associated with the occurrence of vascular complications in patients with type 2 diabetes mellitus. Preliminary evidence has suggested that thiazolidinediones have the ability to modulate circulating levels of this molecule in the hyperglycemic milieu. The aim of this pilot study was to assess the differential effect of 2 different thiazolidinediones-pioglitazone and rosiglitazone-on plasma levels of sRAGE in type 2 diabetes mellitus patients. Sixty type 2 diabetes mellitus subjects were randomly assigned to receive pioglitazone (30 mg/d, n = 19), rosiglitazone (4 mg/d, n = 20), or placebo (medical nutrition therapy, n = 21) for 12 weeks. Changes in plasma glucose, glycosylated hemoglobin, insulin resistance (homeostasis model assessment), total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and sRAGE were evaluated at baseline and after 12 weeks. At 12 weeks, the pioglitazone (P diabetes mellitus patients, pioglitazone-but not rosiglitazone-significantly raised sRAGE, which may contribute to its antiatherogenic effects.

  10. The Adipose Tissue Endocrine Mechanism of the Prophylactic Protective Effect of Pioglitazone in High-Fat Diet-Induced Insulin Resistance

    National Research Council Canada - National Science Library

    Gong, Y; Li, J; Li, C; Mu, Y; Xiao, Y; Tian, H; Pan, C; Liu, Y

    2012-01-01

    ...), or a high-fat diet plus treatment with pioglitazone (P group). Glucose tolerance and insulin resistance were tested at weeks 10 and 11 after starting the diet and, at week 12, adipose, liver and skeletal muscle tissue samples were taken...

  11. A Pilot Trial of Pioglitazone HCl and Tretinoin in ALS: Cerebrospinal Fluid Biomarkers to Monitor Drug Efficacy and Predict Rate of Disease Progression

    Directory of Open Access Journals (Sweden)

    Todd D. Levine

    2012-01-01

    Full Text Available Objectives. To determine if therapy with pioglitazone HCl and tretinoin could slow disease progression in patients with ALS. Levels of tau and pNFH in the cerebrospinal fluid were measured to see if they could serve as prognostic indicators. Methods. 27 subjects on stable doses of riluzole were enrolled. Subjects were randomized to receive pioglitazone 30 mg/d and tretinoin 10 mg/BID for six months or two matching placebos. ALSFRS-R scores were followed monthly. At baseline and at the final visit, lumbar punctures (LPs were performed to measure cerebrospinal fluid (CSF biomarker levels. Results. Subjects treated with tretinoin, pioglitazone, and riluzole had an average rate of decline on the ALSFRS-R scale of −1.02 points per month; subjects treated with placebo and riluzole had a rate of decline of -.86 (P=.18. Over six months of therapy, CSF tau levels decreased in subjects randomized to active treatment and increased in subjects on placebo. Further higher levels of pNF-H at baseline correlated with a faster rate of progression. Conclusion. ALS patients who were treated with tretinoin and pioglitazone demonstrated no slowing on their disease progression. Interestingly, the rate of disease progression was strongly correlated with levels of pNFH in the CSF at baseline.

  12. Independent predictors of retrograde failure in CTO-PCI after successful collateral channel crossing.

    Science.gov (United States)

    Suzuki, Yoriyasu; Muto, Makoto; Yamane, Masahisa; Muramatsu, Toshiya; Okamura, Atsunori; Igarashi, Yasumi; Fujita, Tsutomu; Nakamura, Shigeru; Oida, Akitsugu; Tsuchikane, Etsuo

    2017-07-01

    To evaluate factors for predicting retrograde CTO-PCI failure after successful collateral channel crossing. Successful guidewire/catheter collateral channel crossing is important for the retrograde approach in percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). A total of 5984 CTO-PCI procedures performed in 45 centers in Japan from 2009 to 2012 were studied. The retrograde approach was used in 1656 CTO-PCIs (27.7%). We investigated these retrograde procedures to evaluate factors for predicting retrograde CTO-PCI failure even after successful collateral channel crossing. Successful guidewire/catheter collateral crossing was achieved in 77.1% (n = 1,276) of 1656 retrograde CTO-PCI procedures. Retrograde procedural success after successful collateral crossing was achieved in 89.4% (n = 1,141). Univariate analysis showed that the predictors for retrograde CTO-PCI failure were in-stent occlusion (OR = 1.9829, 95%CI = 1.1783 - 3.3370 P = 0.0088), calcified lesions (OR = 1.9233, 95%CI = 1.2463 - 2.9679, P = 0.0027), and lesion tortuosity (OR = 1.5244, 95%CI = 1.0618 - 2.1883, P = 0.0216). On multivariate analysis, lesion calcification was an independent predictor of retrograde CTO-PCI failure after successful collateral channel crossing (OR = 1.3472, 95%CI = 1.0614 - 1.7169, P = 0.0141). The success rate of retrograde CTO-PCI following successful guidewire/catheter collateral channel crossing was high in this registry. Lesion calcification was an independent predictor of retrograde CTO-PCI failure after successful collateral channel crossing. Devices and techniques to overcome complex CTO lesion morphology, such as lesion calcification, are required to further improve the retrograde CTO-PCI success rate. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Selective cortical control of information flow through different intraspinal collaterals of the same muscle afferent fiber.

    Science.gov (United States)

    Eguibar, J R; Quevedo, J; Jiménez, I; Rudomin, P

    1994-04-18

    We have analyzed in the anesthetized cat the effects of electrical stimulation of the cerebral cortex on the intraspinal threshold of two collaterals belonging to the same muscle spindle or tendon organ afferent fiber. The results obtained provide, for the first time, direct evidence showing that the motor cortex is able to modify, in a highly selective manner, the synaptic effectiveness of individual collaterals of the same primary afferent fiber. This presynaptic control could function as a mechanism that allows funneling of information to specific groups of spinal neurons in the presence of extensive intraspinal branching of the afferent fibers.

  14. Who died? The murder of collaterals related to intimate partner conflict.

    Science.gov (United States)

    Dobash, Russell P; Dobash, R Emerson

    2012-06-01

    Using data from the Murder in Britain Study, the authors focus on murders that are related to intimate partner conflict but involve the killing of a person other than the intimate partner. Intimate partner collateral murders (IPCM) include children, allies, and new partners. The findings expand the number and types of murder associated with intimate partner conflict, characterize the three main types of collaterals, compare the childhood and adulthood of the perpetrators of intimate partner murder [IPM] (n = 104) and IPCM (n = 62), and reflect similarities and differences. Various disciplinary approaches are reflected in the research design, data collection, findings, and conclusions.

  15. A randomized placebo-controlled study on the effects of pioglitazone on cortisol metabolism in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Hermann, Anne Pernille; Hagen, Claus

    2009-01-01

    OBJECTIVE: To investigate possible effects of insulin-sensitizing treatment on cortisol metabolism in insulin-resistant patients with polycystic ovary syndrome (PCOS). DESIGN: Randomized placebo-controlled study. SETTING: Academic tertiary care medical center. PATIENT(S): Thirty insulin-resistant......OBJECTIVE: To investigate possible effects of insulin-sensitizing treatment on cortisol metabolism in insulin-resistant patients with polycystic ovary syndrome (PCOS). DESIGN: Randomized placebo-controlled study. SETTING: Academic tertiary care medical center. PATIENT(S): Thirty insulin......-resistant PCOS patients. INTERVENTION(S): Sixteen weeks of pioglitazone (30 mg/day) or placebo treatment. MAIN OUTCOME MEASURE(S): Twenty-four-hour 20 min integrated blood sampling for measurement of cortisol and 24 h urinary excretion of steroid metabolites. Relative 5alpha-reductase activity was evaluated...... levels. Delta A/E ratio inversely correlated with Delta IGF-I and Delta peak GH during GH stimulation tests. No significant changes were measured in T, DHT, DHEA, DHEAS, 24 h mean cortisol, or urinary excretion of steroid metabolites. CONCLUSION(S): Pioglitazone decreased relative 5alpha...

  16. Development, optimization and in vitro-in vivo evaluation of pioglitazone- loaded jackfruit seed starch-alginate beads.

    Science.gov (United States)

    Nayak, Amit Kumar; Pal, Dilipkumar; Hasnain, Saquib Md

    2013-10-01

    The present investigation describes development and optimization of pioglitazone-loaded jackfruit seed starch (JFSS)-alginate beads by ionotropic-gelation using 3(2) factorial design. The effect of polymer-blend ratio and CaCl2 concentration on the drug encapsulation efficiency (DEE, %), and cumulative drug release after 10 hours (R10h, %) was optimized. The DEE (%) of these beads were 64.80 ± 1.92 to 94.07 ± 3.82 % with sustained in vitro drug release of 64.± 1.83 to 92.66 ± 4.54 % over 10 hours. The in vitro drug release from these beads followed controlled-release pattern with super case-II transport. Particle size range of these beads was 0.77 ± 0.04 to 1.24 ± 0.09 mm. The beads were also characterized by SEM and FTIR. The swelling of these beads was influenced by pH of the test medium. The optimized pioglitazone-loaded JFSS-alginate beads showed significant hypoglycemic effect in alloxan-induced diabetic rats over prolonged period after oral administration.

  17. A COMPARATIVE STUDY OF ROSIGLITAZONE AND PIOGLITAZONE TO EVALUATE THE CARDIOVASCULAR EFFECTS IN HIGH FRUCTOSE DIET INDUCED HYPERTENSIVE RATS

    Directory of Open Access Journals (Sweden)

    Arghya Biswas et al

    2012-09-01

    Full Text Available Thiazolidinediones (TZDs were widely used for the treatment of type 2 diabetes. Recent studies have shown that TZDs have paradoxical effects on cardiovascular diseases. The objective of the present study was to investigate the effect of TZDs (Rosiglitazone and Pioglitazone in High Fructose Diet (HFD induced hypertension in rats. HFD was given for 14 weeks. After 8 weeks of hypertension induction period, treatment phase was started with Rosiglitazone (ROSI 10 and 30 mg/kg, p.o. and Pioglitazone (PIO 10 and 30 mg/kg, p.o. to the respective groups which were continued till 6 weeks. Systolic Blood Pressure (SBP was measured weekly and serum glucose, triglyceride, cholesterol and HDL-C were measured at the end of study period. In HFD fed rats hypertension was observed after 8 weeks. Treatment with the test drugs significantly reversed the changes in serum enzyme levels as well as SBP made by HFD feeding compared to the control group. The study concludes that TZDs possess antihypertensive effect as exhibited in the present experimental settings.

  18. 46 CFR 308.525 - Application for decrease in amount of cash collateral fund, Form MA-305.

    Science.gov (United States)

    2010-10-01

    ... fund, Form MA-305. 308.525 Section 308.525 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF... Insurance § 308.525 Application for decrease in amount of cash collateral fund, Form MA-305. Application for decrease in the amount of the cash collateral deposit fund shall be made on Form MA-305, which may...

  19. 12 CFR 221.117 - When bank in “good faith” has not relied on stock as collateral.

    Science.gov (United States)

    2010-01-01

    ... the margin stock as collateral,” contained in paragraph (2)(iv) of the definition of indirectly... because of fluctuations in market value of the stock, but instead was payable on one or more fixed... stock as collateral. 221.117 Section 221.117 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED)...

  20. Distribution of collateral fibers in the monkey cervical spinal cord detected with diffusion-weighted magnetic resonance imaging

    DEFF Research Database (Denmark)

    Lundell, Henrik; Nielsen, Jens Bo; Ptito, Maurice

    2011-01-01

    in the white matter of the spinal cord is an invalid assumption due to collateral fibers. We also demonstrate that (ii) collateral fibers can be resolved as distinct peaks in the water diffusion propagator in white matter using multi-fiber models. Finally, we show that (iii) crossing fibers are mainly located...

  1. Effects of exenatide, insulin, and pioglitazone on liver fat content and body fat distributions in drug-naive subjects with type 2 diabetes.

    Science.gov (United States)

    Bi, Yan; Zhang, Bing; Xu, Wen; Yang, Huijie; Feng, Wenhuan; Li, Cuiliu; Tong, Guoyu; Li, Ming; Wang, Xin; Shen, Shanmei; Zhu, Bin; Weng, Jianping; Zhu, Dalong

    2014-10-01

    Ectopic accumulation of lipids in nonadipose tissues plays a primary role in the pathogenesis of type 2 diabetes mellitus (T2DM). This study was to examine the effects of exenatide, insulin, and pioglitazone on liver fat content and body fat distributions in T2DM. Thirty-three drug-naive T2DM patients (age 52.7 ± 1.7 years, HbA1c 8.7 ± 0.2 %, body mass index 24.5 ± 0.5 kg/m(2)) were randomized into exenatide, insulin, or pioglitazone for 6 months. Intrahepatic fat (IHF), visceral fat (VF), and subcutaneous fat (SF) were measured using proton nuclear magnetic resonance spectroscopy. Plasma tumor necrosis factor α (TNFα) and adiponectin were assayed by ELISA. HbA1c declined significantly in all three groups. Body weight, waist, and serum triglycerides decreased with exenatide. After interventions, IHF significantly reduced with three treatments (exenatide Δ = -68 %, insulin Δ = -58 %, pioglitazone Δ = -49 %). Exenatide reduced VF (Δ = -36 %) and SF (Δ = -13 %), and pioglitazone decreased VF (Δ = -30 %) with no impact on SF, whereas insulin had no impact on VF or SF. Levels of TNFα (exenatide/insulin/pioglitazone) decreased, and levels of adiponectin (exenatide/pioglitazone) increased. Analysis showed that ΔIHF correlated with ΔHbA1c and Δweight. Besides, ΔIHF correlated with Δtriglycerides and ΔTNFα, but the correlations fell short of significance after BMI adjustment. By linear regression analysis, ΔHbA1c alone explained 41.5 % of the variance of ΔIHF, and ΔHbA1c + Δweight explained 57.6 % of the variance. Liver fat content can be significantly reduced irrespective of using exenatide, insulin, and pioglitazone. Early glycaemic control plays an important role in slowing progression of fatty liver in T2DM.

  2. Modification of MCF-10A cells with pioglitazone and serum-rich growth medium increases soluble factors in the conditioned medium, likely reducing BT-474 cell growth.

    Science.gov (United States)

    Khoo, Boon Yin; Miswan, Noorizan; Balaram, Prabha; Nadarajan, Kalpanah; Elstner, Elena

    2012-01-01

    In the present study, we aimed to preincubate MCF-10A cells with pioglitazone and/or serum-rich growth media and to determine adhesive and non-adhesive interactions of the preincubated MCF-10A cells with BT-474 cells. For this purpose, the MCF-10A cells were preincubated with pioglitazone and/or serum-rich growth media, at appropriate concentrations, for 1 week. The MCF-10A cells preincubated with pioglitazone and/or serum-rich growth media were then co-cultured adhesively and non-adhesively with BT-474 cells for another week. Co-culture of BT-474 cells with the preincubated MCF-10A cells, both adhesively and non-adhesively, reduced the growth of the cancer cells. The inhibitory effect of the preincubated MCF-10A cells against the growth of BT-474 cells was likely produced by increasing levels of soluble factors secreted by the preincubated MCF-10A cells into the conditioned medium, as immunoassayed by ELISA. However, only an elevated level of a soluble factor distinguished the conditioned medium collected from the MCF-10A cells preincubated with pioglitazone and serum-rich growth medium than that with pioglitazone alone. This finding was further confirmed by the induction of the soluble factor transcript expression in the preincubated MCF-10A cells, as determined using real-time PCR, for the above phenomenon. Furthermore, modification of the MCF-10A cells through preincubation did not change the morphology of the cells, indicating that the preincubated cells may potentially be injected into mammary fat pads to reduce cancer growth in patients or to be used for others cell-mediated therapy.

  3. STUDIES ON LINEARTY AND ASSAY USING RP-HPLC AND UV-VISIBLE SPECTROSCOPY FOR THE DRUGS OXCARBAZEPINE AND PIOGLITAZONE BEFORE AND AFTER EXPIRY PERIOD

    Directory of Open Access Journals (Sweden)

    S. Suganya, A. Bright and T.S. Renuga Devi*

    2012-06-01

    Full Text Available The standard for stability and quality of drugs for approval of marketing, are assured by testing and systematic evaluation using different analytical techniques. The drugs are tested in pharma analytical lab involving analysts associated spectra, chromatogram etc , and the results are analyzed leading to fixation of expiry dates. Once the drug crosses its expiry period, its potency is lost and it deteriorates, not only decreasing in therapeutic activity but also turning to be toxic. In the present investigation RP-HPLC and UV-Visible spectroscopic methods are employed for estimation of drugs oxcarbazepine and pioglitazone in tablet dosage form before expiry period and 10-12 months after its expiry. Chromatography was carried out on a C-18 column using a mobile phase of 0.05M KH2PO4 and 0.5 ml Triethylamine buffer solution: methanol: acetonitrile (60:20:20 v/v for oxcarbazepine. The flow rate was 1ml/min with detection at 254nm. For pioglitazone a mobile phase of 0.02 M KH2PO4 buffer: acetonitrile (50:50v/v was used. The flow rate was 2ml/min with detection at 270nm.The calibration curves obtained using HPLC method was linear in the range 160 - 240μgml-1 for oxcarbazepine and 170-280 μgml-1 for pioglitazone. The calibration curves obtained using UV-Visible spectroscopy was linear in the range 10-30 μgml-1 for oxcarbazepine and 10-34 μgml-1 for pioglitazone. Assays of oxcarbazepine found using HPLC technique before expiry was 152.05mg/tablet and after expiry were 138.50mg/tablet. For pioglitazone, before expiry it was 30.85mg/tablet and after expiry 27.60mg/tablet. This was substantiated using UV-Visible spectroscopy.

  4. Influence of health warnings on the use of rosiglitazone and pioglitazone in an area of Spain: A time-series study

    Directory of Open Access Journals (Sweden)

    Eduardo Carracedo-Martínez

    2016-08-01

    Full Text Available Background: Throughout 2007 and January 2008, several glitazones health warnings were published on rosiglitazone myocardial infarction risk. The impact of such warnings on glitazones prevalence of utilization has been extensively studied in the United States but only in one European country (England, which has showed different pattern from US studies. The aim of this study is to evaluate the impact of such safety warnings on glitazones utilization in an area of another European country. Methods: We calculated the number of defined daily doses per thousand inhabitants per day of glitazones each month during the period from 2006 to 2008 in a health area of Spain. We analyzed the data graphically and through a segmented regression analysis. Results: Rosiglitazone defined daily doses per thousand inhabitants per day were growing before the safety warnings, after the warnings a change in trend occurred and rosiglitazone utilization showed a downturn slope. Pioglitazone defined daily doses per thousand inhabitants per day were stable before the safety warnings, and a linear growth was observed after the safety warnings. Throughout the study period, rosiglitazone defined daily doses per thousand inhabitants per day were higher than pioglitazone defined daily doses per thousand inhabitants per day until near the end of 2008. Conclusion: Despite the fact that cardiovascular warnings affected rosiglitazone and not pioglitazone, rosiglitazone was more utilized than pioglitazone until near the end of 2008 which is a pattern similar to the one found in another European studies in England, but very different from studies in the United States, where rosiglitazone was less utilized than pioglitazone from the first month after rosiglitazone cardiovascular safety warnings.

  5. Pioglitazone normalizes insulin signaling in the diabetic rat retina through reduction in tumor necrosis factor α and suppressor of cytokine signaling 3.

    Science.gov (United States)

    Jiang, Youde; Thakran, Shalini; Bheemreddy, Rajini; Ye, Eun-Ah; He, Hui; Walker, Robert J; Steinle, Jena J

    2014-09-19

    Dysfunctional insulin signaling is a key component of type 2 diabetes. Little is understood of the effects of systemic diabetes on retinal insulin signaling. A number of agents are used to treat patients with type 2 diabetes to normalize glucose levels and improve insulin signaling; however, little has been done to investigate the effects of these agents on retinal insulin signal transduction. We hypothesized that pioglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) agonist, would normalize retinal insulin signal transduction through reduced tumor necrosis factor α (TNFα) and suppressor of cytokine signaling 3 (SOCS3) activities in whole retina and retinal endothelial cells (REC) and Müller cells. To test this hypothesis, we used the BBZDR/Wor type 2 diabetic rat model, as well as REC and Müller cells cultured in normoglycemia and hyperglycemic conditions, to investigate the effects of pioglitazone on TNFα, SOCS3, and downstream insulin signal transduction proteins. We also evaluated pioglitazone's effects on retinal function using electroretinogram and markers of apoptosis. Data demonstrate that 2 months of pioglitazone significantly increased electroretinogram amplitudes in type 2 diabetic obese rats, which was associated with improved insulin receptor activation. These changes occurred in both REC and Müller cells treated with pioglitazone, suggesting that these two cell types are key to insulin resistance in the retina. Taken together, these data provide evidence of impaired insulin signaling in type 2 diabetes rats, which was improved by increasing PPARγ activity. Further investigations of PPARγ actions in the retina may provide improved treatment options.

  6. A single dose of PPARγ agonist pioglitazone reduces cortical oxidative damage and microglial reaction following lateral fluid percussion brain injury in rats.

    Science.gov (United States)

    Pilipović, Kristina; Župan, Željko; Dolenec, Petra; Mršić-Pelčić, Jasenka; Župan, Gordana

    2015-06-03

    Neuroprotective actions of the peroxisome proliferator-activated receptor-γ (PPARγ) agonists have been observed in various animal models of the brain injuries. In this study we examined the effects of a single dose of pioglitazone on oxidative and inflammatory parameters as well as on neurodegeneration and the edema formation in the rat parietal cortex following traumatic brain injury (TBI) induced by the lateral fluid percussion injury (LFPI) method. Pioglitazone was administered in a dose of 1mg/kg at 10min after the brain trauma. The animals of the control group were sham-operated and injected by vehicle. The rats were decapitated 24h after LFPI and their parietal cortices were analyzed by biochemical and histological methods. Cortical edema was evaluated in rats sacrificed 48h following TBI. Brain trauma caused statistically significant oxidative damage of lipids and proteins, an increase of glutathione peroxidase (GSH-Px) activity, the cyclooxygenase-2 (COX-2) overexpression, reactive astrocytosis, the microglia activation, neurodegeneration, and edema, but it did not influence the superoxide dismutase activity and the expressions of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha in the rat parietal cortex. Pioglitazone significantly decreased the cortical lipid and protein oxidative damage, increased the GSH-Px activity and reduced microglial reaction. Although a certain degree of the TBI-induced COX-2 overexpression, neurodegeneration and edema decrease was detected in pioglitazone treated rats, it was not significant. In the injured animals, cortical reactive astrocytosis was unchanged by the tested PPARγ agonist. These findings demonstrate that pioglitazone, administered only in a single dose, early following LFPI, reduced cortical oxidative damage, increased antioxidant defense and had limited anti-inflammatory effect, suggesting the need for further studies of this drug in the treatment of TBI.

  7. Changes in bone biological markers after treatment of Iranian diabetic patients with pioglitazone: No relation to polymorphism of PPAR-γ (Pro12Ala).

    Science.gov (United States)

    Namvaran, Fatemeh; Rahimi-Moghaddam, Parvaneh; Azarpira, Negar; Dabbaghmanesh, Mohammad Hossien; Bakhshayeshkaram, Marzieh; Namvaran, Mohamad Mahdi

    2013-04-01

    Thiazolidinediones (TZDs) improves insulin sensitivity by activating the peroxisome proliferator-activated receptor γ (PPAR-g). We aimed to study any association between variation in bone biochemical markers and single nucleotide polymorphism (SNP) in PPAR-γ (Pro12Ala) and investigate if these genetic variants affect bone turnover markers in Iranian diabetic population before and after treatment with pioglitazone. A total of 101 patients (type 2 diabetic (T2D) were treated for 12 weeks with pioglitazone (15 mg/day). Bone Biological markers, osteocalcin, and C-terminal telopeptide of type 1 collagen (CTx) were measured before and after pioglitazone therapy. We genotyped 128 nondiabetic controls and 101 T2D patients as well. Pro12Ala polymorphism in PPAR-γ was done by real-time polymerase chain reaction (RT-PCR) using TaqMan assay. There were statistically significant differences in allele frequencies of Pro12Ala while comparing the controls with T2D subjects. Ala frequency was 7 vs 3%, P = 0.036 and genotypic frequency of Pro/Ala was 5.94 vs 14.06%, P = 0.04. After treatment, the homeostasis model of assessment of insulin resistance (HOMA-IR) as a maker of insulin resistance was significantly decreased (P < 0.001). In respect of bone turnover markers, CTx values decreased and osteocalcin significantly increased. (P < 0.001). Our findings did not reveal a significant association between this polymorphism and bone turnover markers after pioglitazone treatment. The reduced insulin resistance might be the reason that CTx values decreased and osteocalcin increased significantly after short-term pioglitazone treatment. These findings suggest the need for further studies on the possible role of insulin in regulation of bone metabolism.

  8. Changes in bone biological markers after treatment of Iranian diabetic patients with pioglitazone: No relation to polymorphism of PPAR-γ (Pro12Ala

    Directory of Open Access Journals (Sweden)

    Fatemeh Namvaran

    2013-01-01

    Full Text Available Background: Thiazolidinediones (TZDs improves insulin sensitivity by activating the peroxisome proliferator-activated receptor γ (PPAR-g. We aimed to study any association between variation in bone biochemical markers and single nucleotide polymorphism (SNP in PPAR-γ (Pro12Ala and investigate if these genetic variants affect bone turnover markers in Iranian diabetic population before and after treatment with pioglitazone. Materials and Methods: A total of 101 patients (type 2 diabetic (T2D were treated for 12 weeks with pioglitazone (15 mg/day. Bone Biological markers, osteocalcin, and C-terminal telopeptide of type 1 collagen (CTx were measured before and after pioglitazone therapy. We genotyped 128 nondiabetic controls and 101 T2D patients as well. Pro12Ala polymorphism in PPAR-γ was done by real-time polymerase chain reaction (RT-PCR using TaqMan assay. Results: There were statistically significant differences in allele frequencies of Pro12Ala while comparing the controls with T2D subjects. Ala frequency was 7 vs 3%, P = 0.036 and genotypic frequency of Pro/Ala was 5.94 vs 14.06%, P = 0.04. After treatment, the homeostasis model of assessment of insulin resistance (HOMA-IR as a maker of insulin resistance was significantly decreased ( P < 0.001. In respect of bone turnover markers, CTx values decreased and osteocalcin significantly increased. ( P < 0.001. Conclusion: Our findings did not reveal a significant association between this polymorphism and bone turnover markers after pioglitazone treatment. The reduced insulin resistance might be the reason that CTx values decreased and osteocalcin increased significantly after short-term pioglitazone treatment. These findings suggest the need for further studies on the possible role of insulin in regulation of bone metabolism.

  9. HPLC法测定吡格列酮二甲双胍片中盐酸吡格列酮的有关物质%HPLC method for determinnation of the related substances of Pioglitazone hydrochloride of Pioglitazone Metformin Tablets

    Institute of Scientific and Technical Information of China (English)

    雍春; 赵琛

    2012-01-01

    摘要:目的:建立吡格列酮二甲双胍片中盐酸吡格列酮有关物质的高效液相色谱方法。方法:采用为依利特c18色谱柱(250×4.6mm,5um);以水-乙腈-乙酸=550:450:1.2(用氨试液调节pH值至5.8)作为流动相;检测波长为225nm。结果:三批样品(BE1101、BE1102、BE1103)盐酸吡格列酮单个杂质(%)分别为0.15、0.14、0.14;有关物质(%)分别为0.22、0.21、0.21。结论:采用HPLC法测定盐酸吡格列酮有关物质方法简便,结果准确可靠,二甲双胍无干扰。%Purpose: To establish an RP- HPLC method for determinnation of the related substances of Pioglitazone hydrochloride of Pioglitazone Metformin Tablets . Methods: The separation was performed on an Elite C18 column (250 × 4.6 mm, 5 um); and the mobile phase consisted of water - acetonitrile - acetic acid = 550:450:1.2 (ammonia solution adjusted to pH 5.8).The detection was set at 225nm. Results: The three batches of samples (BE1101,BE1102,BE1103) hydrochloride pioglitazone single impurity (%) were 0.15,0.14,0.14; related substances (%) were 0.22,0.21,0.21. Conclusion: the method for determination of pi- oglitazone hydrochloride related substances method is simple, accurate and reliable, metformin no interference.

  10. Functional anatomy of the lateral collateral ligament complex of the elbow

    DEFF Research Database (Denmark)

    Seki, Atsuhito; Olsen, Bo Sanderhoff; Jensen, Steen Lund

    2002-01-01

    A previous anatomic study has revealed that the lateral collateral ligament (LCL) complex of the elbow has a Y-shaped configuration, which consists of a superior, an anterior, and a posterior band. The LCL complex, including the annular ligament, functions as a 3-dimensional (3D) Y-shaped structu...

  11. Direct quantitative assessment of the peripheral artery collateral circulation in patients undergoing angiography.

    Science.gov (United States)

    Traupe, Tobias; Ortmann, Jana; Stoller, Michael; Baumgartner, Iris; de Marchi, Stefano F; Seiler, Christian

    2013-08-13

    Despite the fact that numerous studies have pursued the strategy of improving collateral function in patients with peripheral artery disease, there is currently no method available to quantify collateral arterial function of the lower limb. Pressure-derived collateral flow index (CFIp, calculated as (occlusive pressure-central venous pressure)/(aortic pressure-central venous pressure); pressure values in mm Hg) of the left superficial femoral artery was obtained in patients undergoing elective coronary angiography using a combined pressure/Doppler wire (n=30). Distal occlusive pressure and toe oxygen saturation (Sao2) were measured for 5 minutes under resting conditions, followed by an exercise protocol (repetitive plantar-flexion movements in supine position; n=28). In all patients, balloon occlusion of the superficial femoral artery over 5 minutes was painless under resting conditions. CFIp increased during the first 3 minutes from 0.451±0.168 to 0.551±0.172 (P=0.0003), whereas Sao2 decreased from 98±2% to 93±7% (P=0.004). Maximal changes of Sao2 were inversely related to maximal CFIp (r(2)=0.33, P=0.003). During exercise, CFIp declined within 1 minute from 0.560±0.178 to 0.393±0.168 (Psupply-demand mismatch via collaterals or, alternatively, a steal phenomenon. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT01742455.

  12. CUDA-based acceleration of collateral filtering in brain MR images

    Science.gov (United States)

    Li, Cheng-Yuan; Chang, Herng-Hua

    2017-02-01

    Image denoising is one of the fundamental and essential tasks within image processing. In medical imaging, finding an effective algorithm that can remove random noise in MR images is important. This paper proposes an effective noise reduction method for brain magnetic resonance (MR) images. Our approach is based on the collateral filter which is a more powerful method than the bilateral filter in many cases. However, the computation of the collateral filter algorithm is quite time-consuming. To solve this problem, we improved the collateral filter algorithm with parallel computing using GPU. We adopted CUDA, an application programming interface for GPU by NVIDIA, to accelerate the computation. Our experimental evaluation on an Intel Xeon CPU E5-2620 v3 2.40GHz with a NVIDIA Tesla K40c GPU indicated that the proposed implementation runs dramatically faster than the traditional collateral filter. We believe that the proposed framework has established a general blueprint for achieving fast and robust filtering in a wide variety of medical image denoising applications.

  13. Comparing Main and Collateral Effects of Extinction and Differential Reinforcement of Alternative Behavior

    Science.gov (United States)

    Petscher, Erin Seligson; Bailey, Jon S.

    2008-01-01

    This study evaluated the effects and collateral effects of extinction (EXT) and differential reinforcement of alternative behavior (DRA) interventions with inappropriate vocalizations and work refusal. Both interventions have been used frequently to reduce problem behaviors. The benefits of these interventions have been established yet may be…

  14. Assessment of collateral artery function and growth in a pig model of stepwise coronary occlusion

    NARCIS (Netherlands)

    de Groot, Daphne; Grundmann, Sebastian; Timmers, Leo; Pasterkamp, Gerard; Hoefer, Imo E.

    2011-01-01

    de Groot D, Grundmann S, Timmers L, Pasterkamp G, Hoefer IE. Assessment of collateral artery function and growth in a pig model of stepwise coronary occlusion. Am J Physiol Heart Circ Physiol 300: H408-H414, 2011. First published October 15, 2010; doi: 10.1152/ajpheart.00070.2010.-Therapeutic stimul

  15. Functional Enabling and Physiotherapeutic Treatment of Sportsmen after Injuring Collateral Ligaments of Knee Joint

    Directory of Open Access Journals (Sweden)

    Vukosav Joksimović

    2007-05-01

    Full Text Available Ligamental compound of knee joint represents in mechanical terms, the most complex joint ligamental concatenation. According to seriousness and occurrence of damage, injuries of collateral ligaments can be divided into three degrees. Aim of paper was monitoring and evaluation of results of physiotherapeutic treatment in sportsmen with collateral ligaments injury (CLs of knee joint. The paper comprises 54 sportsmen over the period of four years aged from 16 to 32. Results of paper: 40% (74% injured collateral ligaments while playing game, during football game and 14 (26% while training, 43 (79,6% had collateral ligament injuries of right leg and 11 (20,4% of left leg. In 20( 37% it was a fi rst (1 st degree injury, in 26(48,1 % - second (2nd degree and in 8 (14% third (3rd degree injury. Treatment was conducted over three phases: fi rst - the phase of immobilization ( 2- 6 weeks with K.T.H. of free extremities. Second - the phase of removing immobilization, cryo T.h in combination with available electro- procedures. Third phase was enabling for high- risk physical activities. Results of paper have been classifi ed into four groups: excellent result was observed in 41 ( 76% sportsmen, good in 6 (11 % and satisfactory in 2( 3,8%. Conclusion: Illustrated results obtained on the basis of functional research and after completed rehabilitation allow us to recommend this rehabilitation program as on of the most effi cient ways in treatment of such serious injuries.

  16. Collateral sensitivity to cisplatin in KB-8-5-11 drug-resistant cancer cells.

    LENUS (Irish Health Repository)

    Doherty, Ben

    2014-01-01

    KB-8-5-11 cells are a drug-resistant cervical cell model that overexpresses ABCB1 (P-glycoprotein). KB-8-5-11 has become sensitive to non-ABCB1 substrate cisplatin. Understanding the mechanism of collateral sensitivity to cisplatin may lead to biomarker discovery for platinum sensitivity in patients with cancer.

  17. Collateral ligament reconstruction of the chronic thumb injury with bio-tenodesis screw fixation

    DEFF Research Database (Denmark)

    Gvozdenovic, Robert; Boeckstyns, Michel

    2014-01-01

    We describe a new technique for the reconstruction of chronic lesions of the collateral ligaments of the metacarpophalangeal ligaments of the thumb, using a Bio-Tenodesis screw for the fixation of a tendon graft in a triangular manner with proximal apex and allowing early mobilization, starting 2...

  18. Prognostic value of collateral circulation in patients with unilateral middle cerebral artery occlusion

    Institute of Scientific and Technical Information of China (English)

    梅雨晴

    2014-01-01

    Objective To investigate the characteristics of the collateral circulation in patients with acute cerebral infarction after the middle cerbral artery(MCA)occlusion,and to evaluate its prognostic value.Methods Consecutive series of 118 patients with first-ever stroke after MCA occlusions subjects were retrieved from our hospital and Nanjing Stroke Registry Program between April 2010 and

  19. 45 CFR 1336.67 - Security and collateral: Responsibilities of the Loan Administrator.

    Science.gov (United States)

    2010-10-01

    ...) As a Credit Factor. The availability of collateral security normally is considered an important... interests which may be taken by the lender include, but are not limited to, liens on real or personal... the replacement value of the property secured (whichever is less) must be taken naming the lender...

  20. Gene therapy during cardiac surgery: role of surgical technique to minimize collateral organ gene expression.

    Science.gov (United States)

    Katz, Michael G; Swain, JaBaris D; Fargnoli, Anthony S; Bridges, Charles R

    2010-12-01

    Effective gene therapy for heart failure has not yet been achieved clinically. The aim of this study is to quantitatively assess the cardiac isolation efficiency of the molecular cardiac surgery with recirculating delivery (MCARD™) and to evaluate its efficacy as a means to limit collateral organ gene expression. 10(14) genome copies (GC) of recombinant adeno-associated viral vector 6 encoding green fluorescent protein under control of the cytomegalovirus promoter was delivered to the nine arrested sheep hearts. Blood samples were assessed using real-time quantitative polymerase chain reaction (RT QPCR). Collateral organ gene expression was assessed at four-weeks using immunohistochemical staining. The blood vector GC concentration in the cardiac circuit during complete isolation trended from 9.59±0.73 to 9.05±0.65 (log GC/cm(3)), and no GC were detectable in the systemic circuit (P800-fold (P99% isolation efficiency. Conversely, incomplete isolation resulted in equalization of vector GC concentration in the circuits, leading to robust collateral organ gene expression. MCARD™ is an efficient, clinically translatable myocardial delivery platform for cardiac specific gene therapy. The cardiac surgical techniques utilized are critically important to limit collateral organ gene expression.

  1. PRINSIP 6C (CHARACTER, CAPACITY, CAPITAL, CONDITION OF ECONOMY, COLLATERAL DAN CONSTRAINT DALAM WIRAUSAHA MAHASISWA

    Directory of Open Access Journals (Sweden)

    Henny Sri Astuty

    2015-04-01

    Full Text Available Abstrak: Prinsip 6C (Character, Capacity, Capital, Condition of Economy, Collateral dan Constraint dalam Wirausaha Mahasiswa. Kegiatan wirausaha yang sekarang banyak dilakukan oleh mahasiswa memiliki sisi positif maupun negatif, dari yang berhasil kuliah dan wirausahanya hingga yang gagal semuanya. Untuk ini diperlukan pemahaman tentang prinsip enam C (character, capacity, capital, condition of economy, collateral and constraint yang akan membantu mahasiswa sebagai bekal dalam melakukan kegiatan usahanya. Banyak faktor yang diperoleh dalam prinsip ini yaitu aspek manajemen, pemasaran, produksi, dan keuangan. Kata Kunci: prinsip 6c, wirausaha, mahasiswa Abstract: 6C Principles (Character, Capacity, Capital, Condition of Economy, Collateral and Constraint in Entrepreneurial Students. Entrepreneurial activity that is widely performed by students has two different stories. Some of them are successful on the other hand, the rest of them are fail. Accordingly, it is required an understanding of the 6C principles of the six C (character, capacity, capital, condition of economy, collateral and constraints which will help the students as a preparation in conducting their business activities. Many factors obtained in this principle namely: management, marketing, production, and financial aspects. Keywords: 6C principles, entrepreneurs, students

  2. 78 FR 66621 - Protection of Collateral of Counterparties to Uncleared Swaps; Treatment of Securities in a...

    Science.gov (United States)

    2013-11-06

    ... staff, held a roundtable to discuss individual customer collateral protection with respect to cleared... Commission, through its staff, also met extensively with market participants both prior to and following... provide that turnover of control shall be made promptly upon presentation of a statement in writing...

  3. 吡格列酮对缺血-再灌注损伤大鼠皮质神经元的保护作用%Protective effect of pioglitazone and the role on the cultured cortical neuron after ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    黄昭; 王思荣; 刘继云

    2009-01-01

    Objective To explore the protective effect of proliferator activated receptor-γ (PPAR-γ)activator pioglitazone on the expression of inflammatory cytokines in cultured cortical neurons after ischemia-reperfusion injury and its mechanism. Method The ischemie-reperfusion model was established by deprivating both glucose an oxygen in medium and then gave them back. Medium or that with pioglitazone was added at the beginning of reperfusion. The MTT values of neurons were determined in control or treatment groups, ANOVA was used to detect the expression of PPAR-γ. The expression of tumor necrosis factors-α(TNF-α) and interleukin-lβ(IL-lβ) were detected by Western Blotting. Results Compared to control group, the markedly reduction of MTT values and enhanced expression of PPAR-γ, TNF-a and IL-1β was observed in the ischemia-reperfusion neurons (P < 0.05). After they were treated by pioglitazone, the reduction of MTT values and enhanced expression of TNF-a and IL-1β were prominently reversed by the further activation of PPAR-γ ( P < 0.05). Conclusions Treatment of PPAR-γ activator pioglitazone has protective effect on neurons after ischemia-reperfusion injury. Its mechanism may be associated with the inhibition of inflammation after injury.%目的 探讨过氧化物酶增值物激活受体-γ(PPAR-γ)及其激活剂噻唑烷二酮类药物-吡格列酮(pioglitazone)对缺血.再灌注损伤大鼠皮质神经元肿瘤坏死因子(TNF-α)、白介素(IL-1β)表达的影响.方法 采用原代培养的皮质神经元,通过去除培养液中的糖和氧,模拟缺血缺氧,恢复糖氧供给模拟再灌注.再灌注时分别加用普通培养或含吡格列酮20 μmol/L培养基分别再培养6 h后,以上各组及正常细胞组均采用RT-PCR检测PPAR-γ mRNA表达,MTT法检测细胞活性,同时免疫蛋白印记法检测TNF-α,IL-β蛋白表达.统计学采用单因素方差分析进行统计处理.结果 与正常细胞对照组相比,缺血-再灌注组细

  4. Pioglitazone improves insulin sensitivity, reduces visceral fat and stimulates lipolysis in non diabetic dialyzed patients

    Directory of Open Access Journals (Sweden)

    Anne Zanchi

    2012-06-01

    Full Text Available Insulin resistance is common in dialyzed patients and is associated with increased mortality and protein-energy wasting. The aim of this study was to investigate the effect of pioglitazone (PIO, a powerful insulin sensitizer, on insulin sensitivity, body composition and adipose tissue metabolism, in dialyzed patients. A double blind randomized cross-over study was performed in non diabetic dialysis patients. Each patient followed 2 treatment phases of 16 weeks, starting either with oral PIO 45 mg/d or placebo (PL, and then switched to the other phase. At the end of each phase, patients underwent hyperinsulinemic euglycemic clamps, dual energy X-ray absorptiometry, an abdominal CT, and extensive plasma biochemical analysis. Twelve patients including 8 HD (59.6±4.4 y and 4 PD patients (43.5±3.6 y were recruited. Nine patients completed both phases and 3 patients dropped out (renal transplantation/2 HD and peritonitis/1 PD. PIO was safe and well tolerated. Under PIO, insulin sensitivity improved, as assessed by increased total glucose disposal rate (1.98±0.24 for PIO versus 1.58±0.12 umol/kg/min for PL, p<0.05, and reduced glucose endogenous hepatic production. PIO did not affect post-dialysis body weight, total fat and lean body mass, but significantly reduced visceral adipose tissue (VAT area and the VAT/SAT (subcutaneous adipose tissue ratio. HDL-cholesterol significantly increased. PIO decreased CRP (3.96±1.44 mg/l vs 7.88±2.56, p<0.05, plasma leptin, and dramatically reduced leptin/adiponectin ratio. Glycerol turnover, circulating glycerol and non esterified fatty acids were paradoxically increased. In conclusion, the improvement in insulin sensitivity by PIO, in non diabetic dialyzed patients, was associated with favorable metabolic effects, reduction in inflammation and body fat redistribution. The stimulation of systemic lipolysis was a surprising finding which may reflect adipose tissue remodeling and/or a paradoxical lypolitic

  5. Vector-induced NT-3 expression in rats promotes collateral growth of injured corticospinal tract axons far rostral to a spinal cord injury.

    Science.gov (United States)

    Weishaupt, N; Mason, A L O; Hurd, C; May, Z; Zmyslowski, D C; Galleguillos, D; Sipione, S; Fouad, K

    2014-07-11

    Rewiring the injured corticospinal tract (CST) by promoting connections between CST axons and spared neurons is a strategy being explored experimentally to achieve improved recovery of motor function after spinal cord injury (SCI). Reliable interventions to promote and direct growth of collaterals from injured CST axons are in high demand to promote functionally relevant detour pathways. A promising tool is neurotrophin-3 (NT-3), which has shown growth-stimulating and chemo-attractive effects for spared CST axons caudal to a CST lesion. Yet, efforts to promote growth of injured CST axons rostral to a SCI with NT-3 have been less successful to date. Evidence indicates that immune activation in the local growth environment, either intrinsic or induced by the endotoxin lipopolysaccharide (LPS), can play a decisive role in the CST's responsiveness to NT-3. Here, we test the potential of NT-3 as a tool to enhance and direct collateral growth from the injured CST rostral to a SCI (1) using long-term expression of NT-3 by adeno-associated viral vectors, (2) with and without stimulating the immune system with LPS. Our results indicate that inducing a growth response from injured CST axons into a region of vector-mediated NT-3 expression is possible in the environment of the spinal cord rostral to a SCI, but seems dependent on the distance between the responding axon and the source of NT-3. Our findings also suggest that injured CST axons do not increase their growth response to NT-3 after immune activation with LPS in this environment. In conclusion, this is to our knowledge the first demonstration that NT-3 can be effective at promoting growth of injured CST collaterals far rostral to a SCI. Making NT-3 available in close proximity to CST target axons may be the key to success when using NT-3 to rewire the injured CST in future investigations.

  6. Dopamine D2 Receptors Regulate Collateral Inhibition between Striatal Medium Spiny Neurons

    Science.gov (United States)

    van der Goes, Marie-Sophie; Partridge, John G.; Vicini, Stefano

    2013-01-01

    The principle neurons of the striatum are GABAergic medium spiny neurons (MSNs), whose collateral synapses onto neighboring neurons play critical roles in striatal function. MSNs can be divided by dopamine receptor expression into D1-class and D2-class MSNs, and alterations in D2 MSNs are associated with various pathological states. Despite overwhelming evidence for D2 receptors (D2Rs) in maintaining proper striatal function, it remains unclear how MSN collaterals are specifically altered by D2R activation. Here, we report that chronic D2R stimulation regulates MSN collaterals in vitro by presynaptic and postsynaptic mechanisms. We used corticostriatal cultures from mice in which MSN subtypes were distinguished by fluorophore expression. Quinpirole, an agonist for D2/3 receptors, was used to chronically activate D2Rs. Quinpirole increased the rate and strength of collateral formation onto D2R-containing MSNs as measured by dual whole-cell patch-clamp recordings. Additionally, these neurons were more sensitive to low concentrations of GABA and exhibited an increase in gephyrin puncta density, suggesting increased postsynaptic GABAA receptors. Last, quinpirole treatment increased presynaptic GABA release sites, as shown by increased frequency of sIPSCs and mIPSCs, correlating with increased VGAT (vesicular GABA transporter) puncta. Combined with the observation that there were no detectable differences in sensitivity to specific GABAA receptor modulators, we provide evidence that D2R activation powerfully transforms MSN collaterals via coordinated presynaptic and postsynaptic alterations. As the D2 class of MSNs is highly implicated in Parkinson's disease and other neurological disorders, our findings may contribute to understanding and treating the changes that occur in these pathological states. PMID:23986243

  7. Evaluation of portosystemic collaterals by MDCT-MPR imaging for management of hemorrhagic esophageal varices

    Energy Technology Data Exchange (ETDEWEB)

    Kodama, Hideaki [Department of Medicine and Molecular Science, Division of Frontier Medical Science, Graduate School of Biomedical Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551 (Japan); Aikata, Hiroshi, E-mail: aikata@hiroshima-u.ac.jp [Department of Medicine and Molecular Science, Division of Frontier Medical Science, Graduate School of Biomedical Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551 (Japan); Takaki, Shintaro; Azakami, Takahiro; Katamura, Yoshio; Kawaoka, Tomokazu; Hiramatsu, Akira; Waki, Koji; Imamura, Michio; Kawakami, Yoshiiku; Takahashi, Shoichi [Department of Medicine and Molecular Science, Division of Frontier Medical Science, Graduate School of Biomedical Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551 (Japan); Toyota, Naoyuki; Ito, Katsuhide [Department of Radiology, Division of Medical Intelligence and Informatics, Programs for Applied Biomedicine, Graduate School of Biomedical Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551 (Japan); Chayama, Kazuaki [Department of Medicine and Molecular Science, Division of Frontier Medical Science, Graduate School of Biomedical Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551 (Japan)

    2010-11-15

    Objective: To study the correlation between changes in portosystemic collaterals, evaluated by multidetector-row computed tomography imaging using multiplanar reconstruction (MDCT-MPR), and prognosis in patients with hemorrhagic esophageal varices (EV) after endoscopic treatment. Methods: Forty-nine patients with primary hemostasis for variceal bleeding received radical endoscopic treatment: endoscopic injection sclerotherapy (EIS) or endoscopic variceal ligation (EVL). Patients were classified according to the rate of reduction in feeding vessel diameter on MDCT-MPR images, into the narrowing (n = 24) and no-change (n = 25) groups. We evaluated changes in portosystemic collaterals by MDCT-MPR before and after treatment, and determined rebleeding and survival rates. Results: The left gastric and paraesophageal (PEV) veins were recognized as portosystemic collaterals in 100 and 80%, respectively, of patients with EV on MDCT-MPR images. The rebleeding rates at 1, 2, 3, and 5 years after endoscopic treatment were 10, 15, 23, and 23%, respectively, for the narrowing group, and 17, 24, 35, and 67%, respectively, for the no-change group (P = 0.068). Among no-change group, the rebleeding rate in patients with large PEV was significantly lower than that with small PEV (P = 0.027). The rebleeding rate in patients with small PEV of the no-change group was significantly higher than that in the narrowing group (P = 0.018). There was no significant difference in rebleeding rates between the no-change group with a large PEV and narrowing group (P = 0.435). Conclusion: Changes in portosystemic collaterals evaluated by MDCT-MPR imaging correlate with rebleeding rate. Evaluation of portosystemic collaterals in this manner would provide useful information for the management of hemorrhagic EV.

  8. Role of Genetic Variation in Collateral Circulation in the Evolution of Acute Stroke: A Multimodal Magnetic Resonance Imaging Study.

    Science.gov (United States)

    Kao, Yu-Chieh Jill; Oyarzabal, Esteban A; Zhang, Hua; Faber, James E; Shih, Yen-Yu Ian

    2017-03-01

    No studies have determined the effect of differences in pial collateral extent (number and diameter), independent of differences in environmental factors and unknown genetic factors, on severity of stroke. We examined ischemic tissue evolution during acute stroke, as measured by magnetic resonance imaging and histology, by comparing 2 congenic mouse strains with otherwise identical genetic backgrounds but with different alleles of the Determinant of collateral extent-1 (Dce1) genetic locus. We also optimized magnetic resonance perfusion and diffusion-deficit thresholds by using histological measures of ischemic tissue. Perfusion, diffusion, and T2-weighted magnetic resonance imaging were performed on collateral-poor (congenic-Bc) and collateral-rich (congenic-B6) mice at 1, 5, and 24 hours after permanent middle cerebral artery occlusion. Magnetic resonance imaging-derived penumbra and ischemic core volumes were confirmed by histology in a subset of mice at 5 and 24 hours after permanent middle cerebral artery occlusion. Although perfusion-deficit volumes were similar between strains 1 hour after permanent middle cerebral artery occlusion, diffusion-deficit volumes were 32% smaller in collateral-rich mice. At 5 hours, collateral-rich mice had markedly restored perfusion patterns showing reduced perfusion-deficit volumes, smaller infarct volumes, and smaller perfusion-diffusion mismatch volumes compared with the collateral-poor mice (Pstroke onset. © 2017 American Heart Association, Inc.

  9. Superior vena cava syndrome associated with right-to left shunt through systemic-to-pulmonary venous collaterals

    Energy Technology Data Exchange (ETDEWEB)

    Juan, Yu Hsiang; Saboo, Sachin S.; Anand, Vishal; Chatzizisis, Yiannis S.; Steigner, Michael L. [Brigham and Women' s Hospital, Harvard Medical School, Boston (United States); Lin, Yu Ching [Chang Gung Memorial Hospital, Keelung and Chang Gung University, Keelung (China)

    2014-04-15

    Superior vena cava (SVC) obstruction is associated with the gradual development of venous collaterals. We present a rare form of systemic-to-pulmonary subpleural collateral pathway that developed in the bridging subpleural pulmonary veins in a 54-year-old woman with complete SVC obstruction. This uncommon collateral pathway represents a rare form of acquired right-to-left shunt due to previous pleural adhesions with an increased risk of stroke due to right-to-left venous shunting, which requires lifelong anticoagulation.

  10. Visualization of periventricular collaterals in moyamoya disease with flow-sensitive black-blood magnetic resonance angiography: preliminary experience.

    Science.gov (United States)

    Funaki, Takeshi; Fushimi, Yasutaka; Takahashi, Jun C; Takagi, Yasushi; Araki, Yoshio; Yoshida, Kazumichi; Kikuchi, Takayuki; Miyamoto, Susumu

    2015-01-01

    Fragile abnormal collaterals in moyamoya disease, known as "moyamoya vessels," have rarely been defined. While flow-sensitive black-blood magnetic resonance angiography (FSBB-MRA) is a promising technique for visualizing perforating arteries, as of this writing no other reports exist regarding its application to moyamoya disease. Six adults with moyamoya disease underwent FSBB-MRA. It depicted abnormal collaterals as extended lenticulostriate, thalamic perforating, or choroidal arteries, which were all connected to the medullary or insular artery in the periventricular area and supplied the cortex. This preliminary case series illustrates the potential for FSBB-MRA to reveal abnormal moyamoya vessels, which could be reasonably defined as periventricular collaterals.

  11. TLR4/NF-κB signal pathway mediates pioglitazone protecting human vascular endothelial cells against visfantin-induced injury%TLR4/NF-κB信号转导通路介导吡格列酮在内脂素诱导内皮细胞炎症损伤过程中作用机制的探讨

    Institute of Scientific and Technical Information of China (English)

    何晓乐; 刘军; 张航向; 王宁; 徐荣; 杨洁; 王晓明

    2015-01-01

    Objective To determine the effect of pioglitazone on visfantin-induced inflammatory injury in human vascular endothelial cells and investigate the underlying signal pathway of pioglitazone in improving endothelial functions. Methods Human umbilical vein endothelial cells (HUVECs) were treated by different concentrations of visfantin. Then Western blotting was used to detect the expression of Toll-like receptor4 (TLR4), intercellular cell adhesion molecule-1 (ICAM-1), nuclear factor-κB (NF-κB) and inhibitor of NK- κB-α (IκB-α). Their expression levels were measured again after the cells were respectively exposed to the agonist of peroxisome proliferator activated receptor gamma (PPARγ), pioglitazone. Results Compared with the control group, visfantin enhanced the expression of ICAM-1 in a dose-dependent manner, and also induced TLR4 up-regulation and IκB-α down-regulation (P<0.05), with visfantin at dose of 1×10-5mol/L showing the strongest effect. However, pioglitazone inhibited the above effects of visfatin in a dose-dependent manner, with dose of 20 µmol/L having the maximal effect. Conclusion Pioglitazone exerts protective effect on visfantin-induced inflammatory injury in human vascular endothelial cells, which may be due to its blocking TLR4/NF-κB signal pathway.%目的:观察吡格列酮对内脂素诱导人脐静脉内皮细胞(HUVECs)炎症损伤过程中的影响,探讨吡格列酮改善内皮功能的信号转导机制。方法将HUVECs随机分组,给予不同浓度的内脂素进行诱导,运用蛋白印迹法(Western blotting)检测各组细胞Toll样受体4(TLR4)、细胞间黏附分子-1(ICAM-1)、核因子-κB(NF-κB)和NK-κB抑制蛋白α(IκB-α)的表达;再给予过氧化物酶体增殖物激活受体γ(PPARγ)激动剂吡格列酮,观察各组指标表达变化。结果与正常对照组相比,内脂素呈浓度依赖性地增加ICAM-1含量,下调IκB-α蛋白的表达,同时上调TLR4

  12. METHOD DEVELOPMENT AND VALIDATION OF METFORMIN, GLIMEPIRIDE AND PIOGLITAZONE IN TABLET DOSAGE FORM BY RP-HPLC

    Directory of Open Access Journals (Sweden)

    M Suchitra

    2013-08-01

    Full Text Available A rapid RP-HPLC method was developed and validated for simultaneous estimation of metformin, glimepiride and pioglitazone from pharmaceutical dosage forms. A sensitive chromatographic separation was accomplished on C18 column (100 × 4.6 mm, 5 µ with mobile phase consisting of Methanol: phosphate buffer (pH 3.6 adjusted with ortho phosphoric acid in the ratio of 75:25 v/v, at a flow rate of 1.0 ml / min and monitored at 238 nm. The developed method was validated in terms of accuracy, precision, linearity and limit of detection, limit of quantification, robustness and solution stability. The proposed method can be used for the routine estimation of these drugs in combined pharmaceutical dosage forms.

  13. Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on background metformin and pioglitazone

    Science.gov (United States)

    Forst, T; Guthrie, R; Goldenberg, R; Yee, J; Vijapurkar, U; Meininger, G; Stein, P

    2014-01-01

    Aim The efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, was evaluated in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and pioglitazone. Methods In this randomized, double-blind, phase 3 study, patients (N = 342) received canagliflozin 100 or 300 mg during a 26-week, placebo-controlled, core period and a 26-week, active-controlled extension in which placebo-treated patients were switched to sitagliptin 100 mg. Efficacy comparisons for canagliflozin versus placebo at week 26 are reported, with no comparisons versus sitagliptin at week 52 (sitagliptin used to maintain double-blind and control for safety). Safety data are reported for canagliflozin and placebo/sitagliptin. Results Canagliflozin 100 and 300 mg significantly lowered haemoglobin A1c (HbA1c) compared with placebo at week 26 (−0.89%, −1.03% and −0.26%; p canagliflozin 100 and 300 mg were maintained at week 52 (−0.92% and −1.03%). Relative to placebo, both canagliflozin doses significantly reduced body weight (−2.5 and −3.5 kg), fasting plasma glucose and systolic blood pressure (BP) at week 26 (p canagliflozin 100 and 300 mg and placebo/sitagliptin; AE-related discontinuation and serious AE rates were low. Incidences of genital mycotic infections and AEs related to osmotic diuresis and volume depletion were higher with canagliflozin than placebo/sitagliptin. Conclusion Canagliflozin improved glycaemic control, reduced body weight and systolic BP, and was generally well tolerated in patients with T2DM on metformin and pioglitazone over 52 weeks. PMID:24528605

  14. Different skeletal effects of the peroxisome proliferator activated receptor (PPAR)alpha agonist fenofibrate and the PPARgamma agonist pioglitazone.

    Science.gov (United States)

    Syversen, Unni; Stunes, Astrid K; Gustafsson, Björn I; Obrant, Karl J; Nordsletten, Lars; Berge, Rolf; Thommesen, Liv; Reseland, Janne E

    2009-03-30

    All the peroxisome proliferator activated receptors (PPARs) are found to be expressed in bone cells. The PPARgamma agonist rosiglitazone has been shown to decrease bone mass in mice and thiazolidinediones (TZDs) have recently been found to increase bone loss and fracture risk in humans treated for type 2 diabetes mellitus. The aim of the study was to examine the effect of the PPARalpha agonist fenofibrate (FENO) and the PPARgamma agonist pioglitazone (PIO) on bone in intact female rats. Rats were given methylcellulose (vehicle), fenofibrate or pioglitazone (35 mg/kg body weight/day) by gavage for 4 months. BMC, BMD, and body composition were measured by DXA. Histomorphometry and biomechanical testing of excised femurs were performed. Effects of the compounds on bone cells were studied. The FENO group had higher femoral BMD and smaller medullary area at the distal femur; while trabecular bone volume was similar to controls. Whole body BMD, BMC, and trabecular bone volume were lower, while medullary area was increased in PIO rats compared to controls. Ultimate bending moment and energy absorption of the femoral shafts were reduced in the PIO group, while similar to controls in the FENO group. Plasma osteocalcin was higher in the FENO group than in the other groups. FENO stimulated proliferation and differentiation of, and OPG release from, the preosteoblast cell line MC3T3-E1. We show opposite skeletal effects of PPARalpha and gamma agonists in intact female rats. FENO resulted in significantly higher femoral BMD and lower medullary area, while PIO induced bone loss and impairment of the mechanical strength. This represents a novel effect of PPARalpha activation.

  15. Different skeletal effects of the peroxisome proliferator activated receptor (PPARα agonist fenofibrate and the PPARγ agonist pioglitazone

    Directory of Open Access Journals (Sweden)

    Nordsletten Lars

    2009-03-01

    Full Text Available Abstract Background All the peroxisome proliferator activated receptors (PPARs are found to be expressed in bone cells. The PPARγ agonist rosiglitazone has been shown to decrease bone mass in mice and thiazolidinediones (TZDs have recently been found to increase bone loss and fracture risk in humans treated for type 2 diabetes mellitus. The aim of the study was to examine the effect of the PPARα agonist fenofibrate (FENO and the PPARγ agonist pioglitazone (PIO on bone in intact female rats. Methods Rats were given methylcellulose (vehicle, fenofibrate or pioglitazone (35 mg/kg body weight/day by gavage for 4 months. BMC, BMD, and body composition were measured by DXA. Histomorphometry and biomechanical testing of excised femurs were performed. Effects of the compounds on bone cells were studied. Results The FENO group had higher femoral BMD and smaller medullary area at the distal femur; while trabecular bone volume was similar to controls. Whole body BMD, BMC, and trabecular bone volume were lower, while medullary area was increased in PIO rats compared to controls. Ultimate bending moment and energy absorption of the femoral shafts were reduced in the PIO group, while similar to controls in the FENO group. Plasma osteocalcin was higher in the FENO group than in the other groups. FENO stimulated proliferation and differentiation of, and OPG release from, the preosteoblast cell line MC3T3-E1. Conclusion We show opposite skeletal effects of PPARα and γ agonists in intact female rats. FENO resulted in significantly higher femoral BMD and lower medullary area, while PIO induced bone loss and impairment of the mechanical strength. This represents a novel effect of PPARα activation.

  16. Management of Medial Collateral Ligament Injury During Primary Total Knee Arthroplasty: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Paul Della Torre, MD

    2014-07-01

    Full Text Available Medial collateral ligament injury during primary total knee arthroplasty is a recognised complication potentially resulting in valgus instability, suboptimal patient outcomes and a higher rate of revision or reoperation. Options for management include primary repair with or without augmentation, reconstruction or immediate conversion to prosthesis with greater constraint, in conjunction with various postoperative rehabilitation protocols. Inconsistent recommendations throughout the orthopaedic literature have made the approach to managing this complication problematic. The objective of this study was to review the available literature to date comparing intraoperative and postoperative management options for primary total knee arthroplasty complicated by recognised injury to the medial collateral ligament. This systematic literature review was prospectively registered with PROSPERO (#CRD42014008866 and performed in accordance with PRISMA guidelines including a PRISMA flow diagram. Five articles satisfied the inclusion criteria. Each was a retrospective, observational cohort or case series with small numbers reported, inconsistent methodology and incompletely reported outcomes. Four of the five studies managing medial collateral ligament injury during total knee arthroplasty (47/84 patients with direct repair with or without autograft augmentation reported good outcomes with no revision or reoperation required for symptomatic instability over a follow-up period of 16 months to almost 8 years. The fifth study with a follow-up to 10 years and a high rate of conversion to unlinked semi constrained total knee arthroplasty implant (30/37 patients reported a greater incidence of revision due to instability, in patients in whom the medial collateral ligament injury was directly repaired without added constraint. Overall balance of evidence is in favour of satisfactory outcomes without symptomatic instability following direct repair with or without

  17. Predictors of Ulnar Collateral Ligament Reconstruction in Major League Baseball Pitchers.

    Science.gov (United States)

    Whiteside, David; Martini, Douglas N; Lepley, Adam S; Zernicke, Ronald F; Goulet, Grant C

    2016-09-01

    Ulnar collateral ligament (UCL) reconstruction surgeries in Major League Baseball (MLB) have increased significantly in recent decades. Although several risk factors have been proposed, a scientific consensus is yet to be reached, providing challenges to those tasked with preventing UCL injuries. To identify significant predictors of UCL reconstruction in MLB pitchers. Case control study; Level of evidence, 3. Demographic and pitching performance data were sourced from public databases for 104 MLB pitchers who underwent UCL reconstruction surgery and 104 age- and position-matched controls. These variables were compared between groups and inserted into a binary logistic regression to identify significant predictors of UCL reconstruction. Two machine learning models (naïve Bayes and support vector machine) were also employed to predict UCL reconstruction in this cohort. The binary linear regression model was statistically significant (χ(2)(12) = 33.592; P = .001), explained 19.9% of the variance in UCL reconstruction surgery, and correctly classified 66.8% of cases. According to this model, (1) fewer days between consecutive games, (2) a smaller repertoire of pitches, (3) a less pronounced horizontal release location, (4) a smaller stature, (5) greater mean pitch speed, and (6) greater mean pitch counts per game were all significant predictors of UCL reconstruction. More specifically, an increase in mean days between consecutive games (odds ratio [OR], 0.685; 95% CI, 0.542-0.865) or number of unique pitch types thrown (OR, 0.672; 95% CI, 0.492-0.917) was associated with a significantly smaller likelihood of UCL reconstruction. In contrast, an increase in mean pitch speed (OR, 1.381; 95% CI, 1.103-1.729) or mean pitches per game (OR, 1.020; 95% CI, 1.007-1.033) was associated with significantly higher odds of UCL reconstruction surgery. The naïve Bayes classifier predicted UCL reconstruction with an accuracy of 72% and the support vector machine classifier with an

  18. Blood flow and vascular reactivity in collaterally perfused brain tissue. Evidence of an ischemic penumbra in patients with acute stroke

    DEFF Research Database (Denmark)

    Olsen, T S; Larsen, B; Herning, M;

    1983-01-01

    ischemic low flow areas were a constant finding in the collaterally perfused tissue. In 6 of the patients, the collaterally perfused part of the brain had low flow values comparable to those of an "ischemic penumbra" (viable, but functionally depressed brain tissue due to inadequate perfusion......In a group of 48 patients with completed stroke, 8 patients had viable collaterally perfused brain tissue which was accessible for rCBF recordings with a two dimensional technique. All 8 had deep subcortical infarcts on CT-scan, and angiographic occlusion of the arteries normally supplying...... the infarcted territory. The brain tissue overlying the deep infarcts appeared normal on CT-scan and was supplied by collateral circulation. rCBF was measured in all within 72 hours after the stroke. The intra-carotid Xe-133 injection method and a 254 multidetector camera were used to study rCBF. Relatively...

  19. Spatially Interpolated Disease Prevalence Estimation Using Collateral Indicators of Morbidity and Ecological Risk

    Directory of Open Access Journals (Sweden)

    Peter Congdon

    2013-10-01

    Full Text Available This paper considers estimation of disease prevalence for small areas (neighbourhoods when the available observations on prevalence are for an alternative partition of a region, such as service areas. Interpolation to neighbourhoods uses a kernel method extended to take account of two types of collateral information. The first is morbidity and service use data, such as hospital admissions, observed for neighbourhoods. Variations in morbidity and service use are expected to reflect prevalence. The second type of collateral information is ecological risk factors (e.g., pollution indices that are expected to explain variability in prevalence in service areas, but are typically observed only for neighbourhoods. An application involves estimating neighbourhood asthma prevalence in a London health region involving 562 neighbourhoods and 189 service (primary care areas.

  20. Outcome review on the percutaneous release of the proximal interphalangeal joint accessory collateral ligaments

    Directory of Open Access Journals (Sweden)

    Sonja Cerovac

    2009-10-01

    Full Text Available The percutaneous release of accessory collateral ligaments was introduced in 1986 as a safe and quick procedure to be attempted before open, more extensive joint release in the treatment of proximal interphalangeal joint flexion contracture. Our study analyzed the long-term results and patient satisfaction following a percutaneous release in 30 joints after a mean follow-up period of 34 months. In one half of cases the preoperative joint flexion deformity was reduced from 78° to 34°. The best results were observed in patients with osteoarthritis and stiff, immobilized joints. In patients with inflammatory arthritides, marked intraoperative correction was maintained rarely, joint contractures recurred early, and patients were unsatisfied. There were no intraoperative complications. Percutaneous release of the accessory collateral ligaments can produce a long lasting correction of the joint contracture, but careful patient selection and strict postoperative rehabilitation are essential for favorable outcome.

  1. [Practice on the case-based teaching innovation of Science of Meridians, Collaterals and Acupoints].

    Science.gov (United States)

    Yin, Zhen-Jin; Zhang, Shu-Feng; Yan, Yuan-Jie; Bao, Hong-Ling; Wang, Bei-Bei

    2012-12-01

    The case-based teaching method which is applied to the teaching of Science of Meridians, Collaterals and Acupoints is discussed in this paper, in which the typical cases such as the growth of the acupuncture-moxibustion eminent physicians, the application of acupoints by the eminent physicians and the experiences in the acupoint combination are integrated. The students are instructed to launch the clinical practical activity through establishing the clinical base of Science of Meridians, Collaterals and Acupoints, in association with the true cases. It is proved that the case-based teaching method can promote the training of the manipulation techniques of the students and the inheritance of the experiences of eminent physicians in higher education.

  2. Posttraumatic incarceration of medial collateral ligament into knee joint with anterior cruciate ligament injury

    Institute of Scientific and Technical Information of China (English)

    Sunil Gurpur Kini; Karel du Pre; Warwick Bruce

    2015-01-01

    Medial collateral ligament of the knee is an important coronal stabiliser and often injured in isolation or as combination of injuries.The article reports a case of incarcerated medial collateral ligament (MCL) injury in combination with anterior cruciate ligament (ACL) injury in 20 year old male who presented to us 4 weeks after injury.Clinical examination and MRI was correlated to complete ACL tear with torn distal MCL and incarceration into the joint.Patient was taken up for ACL hamstring graft reconstruction with mini-arthrotomy and repair of the torn MCL.Patient was followed up with dedicated rehabilitation protocol with good functional results.At one year follow-up, patient exhibited full range of motion with negative Lachman, Pivot shift and valgus stress tests.This article highlights the rare pattern of MCL tear and also reviews the literature on this pattern of injury.

  3. Placement of a port catheter through collateral veins in a patient with central venous occlusion.

    Science.gov (United States)

    Teichgräber, Ulf Karl-Martin; Streitparth, Florian; Gebauer, Bernhard; Benter, Thomas

    2010-04-01

    Long-term utilization of central venous catheters (CVCs) for parenteral nutrition has a high incidence of central venous complications including infections, occlusions, and stenosis. We report the case of a 31-year-old woman presenting with a malabsorption caused by short gut syndrome due to congenital aganglionic megacolon. The patient developed a chronic occlusion of all central neck and femoral veins due to long-term use of multiple CVCs over more than 20 years. In patients with central venous occlusion and venous transformation, the implantation of a totally implanted port system by accessing collateral veins is an option to continue long-term parenteral nutrition when required. A 0.014-in. Whisper guidewire (Terumo, Tokyo) with high flexibility and steerability was chosen to maneuver and pass through the collateral veins. We suggest this approach to avoid unfavorable translumbar or transhepatic central venous access and to conserve the anatomically limited number of percutaneous access sites.

  4. Portal hypertension: Imaging of portosystemic collateral pathways and associated image-guided therapy.

    Science.gov (United States)

    Bandali, Murad Feroz; Mirakhur, Anirudh; Lee, Edward Wolfgang; Ferris, Mollie Clarke; Sadler, David James; Gray, Robin Ritchie; Wong, Jason Kam

    2017-03-14

    Portal hypertension is a common clinical syndrome, defined by a pathologic increase in the portal venous pressure. Increased resistance to portal blood flow, the primary factor in the pathophysiology of portal hypertension, is in part due to morphological changes occurring in chronic liver diseases. This results in rerouting of blood flow away from the liver through collateral pathways to low-pressure systemic veins. Through a variety of computed tomographic, sonographic, magnetic resonance imaging and angiographic examples, this article discusses the appearances and prevalence of both common and less common portosystemic collateral channels in the thorax and abdomen. A brief overview of established interventional radiologic techniques for treatment of portal hypertension will also be provided. Awareness of the various imaging manifestations of portal hypertension can be helpful for assessing overall prognosis and planning proper management.

  5. IMATERALISASI JAMINAN BENDA DALAM BENTUK CASH COLLATERAL SEBAGAI JAMINAN PROYEK INFRA STRUKTUR MELALUI MEKANISME SWIFT

    Directory of Open Access Journals (Sweden)

    Tarsisius Murwaji

    2013-01-01

    Full Text Available The construction of infrastructure projects require large expenses. The cost for the project loan is usually derived from international banks. Legal issues, among others: we do not guarantee the legal system conducive to use in large financing; corporate body and banking institutions we considered to be of international standard, and our le-gal system is regarded as the country risk. The other hand many people of Indonesia who have collateral material, usually pure gold (precious metals that have been diimaterialization and included in the accounts of foreign banks. Such guarantees may be used as the basis of the issuance of bank guarantees and through the mechanism of Society Worldwide Interbank Financial Telecommunications (SWIFT can be used as loan collateral banks in Indonesia.

  6. IMATERALISASI JAMINAN BENDA DALAM BENTUK CASH COLLATERAL SEBAGAI JAMINAN PROYEK INFRA STRUKTUR MELALUI MEKANISME SWIFT

    Directory of Open Access Journals (Sweden)

    Tarsisius Murwaji

    2013-10-01

    Full Text Available The construction of infrastructure projects require large expenses. The cost for the project loan is usually derived from international banks. Legal issues, among others: we do not guarantee the legal system conducive to use in large financing; corporate body and banking institutions we considered to be of international standard, and our le-gal system is regarded as the country risk. The other hand many people of Indonesia who have collateral material, usually pure gold (precious metals that have been diimaterialization and included in the accounts of foreign banks. Such guarantees may be used as the basis of the issuance of bank guarantees and through the mechanism of Society Worldwide Interbank Financial Telecommunications (SWIFT can be used as loan collateral banks in Indonesia. Key words: bank guaranty, SWIFT, security law, international banking system

  7. Association of pioglitazone treatment with decreased bone mineral density in obese premenopausal patients with polycystic ovary syndrome: a randomized, placebo-controlled trial

    DEFF Research Database (Denmark)

    Glintborg, D.; Andersen, Mikael; Hagen, C.;

    2008-01-01

    .948-1.341) g/cm(2) (average decline 1.1%) and femoral neck 0.966 (0.767-1.217) vs. 0.952 (0.760-1.192) g/cm(2) (average decline 1.4%), both P ..., sex hormones, and body composition. CONCLUSION: Pioglitazone treatment was followed by decreased lumbar and hip BMD and decreased measures of bone turnover in a premenopausal study population relatively protected from bone mineral loss Udgivelsesdato: 2008/5...

  8. Improved Insulin Sensitivity during Pioglitazone Treatment Is Associated with Changes in IGF-I and Cortisol Secretion in Type 2 Diabetes and Impaired Glucose Tolerance.

    Science.gov (United States)

    Arnetz, Lisa; Rajamand Ekberg, Neda; Höybye, Charlotte; Brismar, Kerstin; Alvarsson, Michael

    2013-01-01

    Background. Hypercortisolism and type 2 diabetes (T2D) share clinical characteristics. We examined pioglitazone's effects on the GH-IGF-I and HPA axes in men with varying glucose intolerance. Methods. 10 men with T2D and 10 with IGT received pioglitazone 30-45 mg for 12 weeks. OGTT with microdialysis in subcutaneous adipose tissue and 1 μg ACTH-stimulation test were performed before and after. Glucose, insulin, IGF-I, IGFBP1, and interstitial measurements were analyzed during the OGTT. Insulin sensitivity was estimated using HOMA-IR. Results. HOMA-IR improved in both groups. IGF-I was initially lower in T2D subjects (P = 0.004) and increased during treatment (-1.4 ± 0.5 to -0.5 ± 0.4 SD; P = 0.007); no change was seen in IGT (0.4 ± 39 SD before and during treatment). Fasting glycerol decreased in T2D (P = 0.038), indicating reduced lipolysis. Fasting cortisol decreased in T2D (400 ± 30 to 312 ± 25 nmol/L; P = 0.041) but increased in IGT (402 ± 21 to 461 ± 35 nmol/L; P = 0.044). Peak cortisol was lower in T2D during treatment (599 ± 32 to 511 ± 43, versus 643 ± 0.3 to 713 ± 37 nmol/L in IGT; P = 0.007). Conclusions. Pioglitazone improved adipose tissue and liver insulin sensitivity in both groups. This may explain increased IGF-I in T2D. Pioglitazone affected cortisol levels in both groups but differently, suggesting different mechanisms for improving insulin sensitivity between T2D and IGT.

  9. Liquid Chromatographic Methods for the Determination of Vildagliptin in the Presence of its Synthetic Intermediate and the Simultaneous Determination of Pioglitazone Hydrochloride and Metformin Hydrochloride

    OpenAIRE

    El-Bagary, Ramzia I.; Elkady, Ehab F.; Ayoub, Bassam M.

    2011-01-01

    Two reversed-phase liquid chromatographic (RP-LC) methods are described for the determination of two binary mixtures of hypoglycemic agents. In the first method, vildagliptin (VDG) was determined in the presence of 3-amino-1-adamantanol (AAD), a synthetic intermediate and impurity of VDG. In the second method, pioglitazone hydrochloride (PGZ) and metformin hydrochloride (MET) were simultaneously determined in their binary mixture. Chromatographic separation in the two methods was achieved on ...

  10. Effect of Pioglitazone on Serum Uric Acid Levels in Newly Diagnosed, Drug-Naïve Patients with Type 2 Diabetes.

    Science.gov (United States)

    Kutoh, Eiji; Hori, Tadataka

    2012-12-05

    Objectives. The aim of this study was to investigate the effect of pioglitazone on serum uric acid (UA) levels and several diabetic parameters in drug-naïve subjects with type 2 diabetes mellitus (T2DM). Patients and Methods. The patients (n = 68) received 7.5-30 mg/day pioglitazone monotherapy. They were divided into three groups based on their baseline UA levels (low, medium, and high). These parameters were followed for 12 weeks. Results. At baseline, HbA1c and fasting blood glucose (FBG) levels were in negative proportion to those of UA, while homeostasis model assessment-beta (HOMA-B) levels were in proportion to those of UA. Insulin, homeostasis model assessment-R (HOMA-R), and body mass index (BMI) levels had a tendency to be in proportion to those of UA. While similar glycemic effects were observed in all the groups, UA levels significantly decreased in the high UA group while they insignificantly increased in the low UA group. Multiple regression analysis revealed that the baseline UA level and age were the significant determinants for the changes of UA levels. In the high UA group, significant decreases of insulin and HOMA-R levels were observed, and their changes (Δ) were significantly correlated with those of UA. Other parameters including insulin, HOMA-R, HOMA-B, and BMI were also differentially regulated between these groups. Conclusions. These results indicate that (1) while similar glycemic effects were observed, distinct regulations of UA and other diabetic parameters were observed with pioglitazone depending on the baseline UA levels; (2) pioglitazone downregulated hyperuricemia by possibly relieving insulin resistance; and (3) the level of UA together with other parameters might provide some diabetic characteristics of the subjects.

  11. PPARγ agonist pioglitazone improves cerebellar dysfunction at pre-Aβ deposition stage in APPswe/PS1dE9 Alzheimer's disease model mice

    Energy Technology Data Exchange (ETDEWEB)

    Toba, Junya; Nikkuni, Miyu [Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Ishizeki, Masato [Laboratory for Neurophysiology, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Yoshii, Aya; Watamura, Naoto [Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Inoue, Takafumi [Laboratory for Neurophysiology, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Ohshima, Toshio, E-mail: ohshima@waseda.jp [Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan)

    2016-05-13

    Alzheimer's disease (AD) is one of the best known neurodegenerative diseases; it causes dementia and its pathological features include accumulation of amyloid β (Aβ) and neurofibrillary tangles (NFTs) in the brain. Elevated Cdk5 activity and CRMP2 phosphorylation have been reported in the brains of AD model mice at the early stage of the disease, but the significance thereof in human AD remains unelucidated. We have recently reported that Aβ accumulation in the cerebellum of AD model APPswe/PS1dE9 (APP/PS1) mice, and cerebellar dysfunctions, such as impairment of motor coordination ability and long-term depression (LTD) induction, at the pre-Aβ accumulation stage. In the present study, we found increased phosphorylation levels of CRMP2 as well as increased p35 protein levels in the cerebellum of APP/PS1 mice. Interestingly, we show that pioglitazone, an agonist of peroxisome proliferator-activated receptor γ, normalized the p35 protein and CRMP2 phosphorylation levels in the cerebellum. Impaired motor coordination ability and LTD in APP/PS1 mice were ameliorated by pioglitazone treatment at the pre-Aβ accumulation stage. These results suggest a correlation between CRMP2 phosphorylation and AD pathophysiology, and indicate the effectiveness of pioglitazone treatment at the pre-Aβ accumulation stage in AD model mice. -- Highlights: •Phosphorylation level of CRMP2 increased in the cerebellum of APP/PS1 mice. •p35 protein levels increased in the cerebellum of APP/PS1 mice. •Pioglitazone treatment improved cerebellar dysfunction of APP/PS1 mice.

  12. FLAIR vascular hyperintensities and dynamic 4D angiograms for the estimation of collateral blood flow in posterior circulation occlusion

    Energy Technology Data Exchange (ETDEWEB)

    Foerster, Alex; Wenz, Holger; Kerl, Hans Ulrich; Al-Zghloul, Mansour; Habich, Sonia; Groden, Christoph [University of Heidelberg, Department of Neuroradiology, Universitaetsmedizin Mannheim, Mannheim (Germany)

    2014-09-15

    The objectives of this paper are to assess collateral blood flow in posterior circulation occlusion by MRI-based approaches (fluid-attenuated inversion recovery (FLAIR) vascular hyperintensities (FVHs), collateralization on dynamic 4D angiograms) and investigate its relation to ischemic lesion size and growth. In 28 patients with posterior cerebral artery (PCA) and 10 patients with basilar artery (BA) occlusion, MRI findings were analyzed, with emphasis on distal FVH and collateralization on dynamic 4D angiograms. In PCA occlusion, distal FVH was observed in 18/29 (62.1 %), in BA occlusion, in 8/10 (80 %) cases. Collateralization on dynamic 4D angiograms was graded 1 in 8 (27.6 %) patients, 2 in 1 (3.4 %) patient, 3 in 12 (41.4 %) patients, and 4 in 8 (27.6 %) patients with PCA occlusion and 0 in 1 (10 %) patient, 2 in 3 (30 %) patients, 3 in 1 (10 %) patient, and 4 in 5 (50 %) patients with BA occlusion. FVH grade showed neither correlation with initial or follow-up diffusion-weighted image (DWI) lesion size nor DWI-perfusion-weighted imaging (PWI) mismatch ratio. Collateralization on dynamic 4D angiograms correlated inversely with initial DWI lesion size and moderately with the DWI-(PWI) mismatch ratio. The combination of distal FVH and collateralization grade on dynamic 4D angiograms correlated inversely with initial as well as follow-up DWI lesion size and highly with the DWI-PWI mismatch ratio. In posterior circulation occlusion, FVH is a frequent finding, but its prognostic value is limited. Dynamic 4D angiograms are advantageous to examine and graduate collateral blood flow. The combination of both parameters results in an improved characterization of collateral blood flow and might have prognostic relevance. (orig.)

  13. Endovascular therapy of ruptured distal anterior choroidal artery aneurysm associated with moyamoya pattern collateralization secondary to middle cerebral artery occlusion

    Directory of Open Access Journals (Sweden)

    Hidenori Oishi

    2013-01-01

    Full Text Available We report a case of a ruptured distal anterior choroidal artery (AChoA aneurysm associated with moyamoya pattern collateralization secondary to the middle cerebral artery occlusion. Patient was successfully treated with the coil embolization of the distal AChoA. This case supports the feasibility and efficacy of the endovascular therapy for the distal AChoA aneurysms in patients with MCA occlusion with moyamoya pattern collateralization.

  14. Post traumatic osteoma of tibial insertion of medial collateral ligament of knee joint.

    Science.gov (United States)

    Shanker, V S; Gadikoppula, S; Loeffler, M D

    1998-03-01

    Two cases are presented of post traumatic para-articular osteoma developing at the site of tibial attachment of the medial collateral ligament of knee joint. These occurred after injuries sustained while playing football and in one case the ossified mass was treated with surgical excision for unresolved symptoms after conservative measures. A comparison is made with Pellegrini Stieda disease, which is a similar affection of the femoral insertion of the medial ligament of the knee joint.

  15. Post traumatic osteoma of tibial insertion of medial collateral ligament of knee joint

    OpenAIRE

    Shanker, V. S.; Gadikoppula, S.; Loeffler, M. D.

    1998-01-01

    Two cases are presented of post traumatic para-articular osteoma developing at the site of tibial attachment of the medial collateral ligament of knee joint. These occurred after injuries sustained while playing football and in one case the ossified mass was treated with surgical excision for unresolved symptoms after conservative measures. A comparison is made with Pellegrini Stieda disease, which is a similar affection of the femoral insertion of the medial ligament of the knee joint....

  16. Relation between prognosis and collateral circulation or recanalization in occlusive cerebral vascular diseases

    Energy Technology Data Exchange (ETDEWEB)

    Saito, Yuko (Tokyo Women' s Medical Coll. (Japan))

    1982-09-01

    CT images and angiograms were compared, in occlusive cerebral vascular diseases with complete stroke in the region of internal carotid artery, and following subjects were discussed. 1) Relation between size of final low density area on CT and prognosis. 2) Effectiveness of collateral circulation and recanalization to the low density area on CT in the territory of occluded artery. For the subject 1,100 cases of infarction of the region of middle cerebral artery were chosen at random, and the prognosis was compared with the size of low density area on CT. For the subject 2,186 cases of infarction in the region on internal carotid artery were selected, and CT images and angiograms were compared, considering the duration between stroke and angiography. With these studies, following conclusions were obtained. There is tendency that cases with the smaller low density areas on CT have the better prognosis. The low density on CT appears inside of the territory of the occluded artery. When there is neither collateral circulation nor recanalization, appearance of the low density on CT is not avoided. Collateral circulation or recanalization is able to rescue the affected area from appearance of low density on CT, even if it is formed later than 6 hours after ictus. The critical period when collateral circulation or recanalization effects on the involved area is variable depending on each cases, but it is suspected to be 24 or 72 hours after onset. Blood supply which begins later than 73 hours after occlusion of artery does not effect on the involved area.

  17. Blood ammonia levels in liver cirrhosis: a clue for the presence of portosystemic collateral veins

    OpenAIRE

    Tripodi Francesca; Milan Graziella; de Leone Annalisa; Giaquinto Sabrina; Esposito Pasquale; Citro Vincenzo; Tarantino Giovanni; Cirillo Michele; Lobello Roberto

    2009-01-01

    Abstract Background Portal hypertension leads to the formation of portosystemic collateral veins in liver cirrhosis. The resulting shunting is responsible for the development of portosystemic encephalopathy. Although ammonia plays a certain role in determining portosystemic encephalopathy, the venous ammonia level has not been found to correlate with the presence or severity of this entity. So, it has become partially obsolete. Realizing the need for non-invasive markers mirroring the presenc...

  18. Blood ammonia levels in liver cirrhosis: a clue for the presence of portosystemic collateral veins

    Directory of Open Access Journals (Sweden)

    Tripodi Francesca

    2009-03-01

    Full Text Available Abstract Background Portal hypertension leads to the formation of portosystemic collateral veins in liver cirrhosis. The resulting shunting is responsible for the development of portosystemic encephalopathy. Although ammonia plays a certain role in determining portosystemic encephalopathy, the venous ammonia level has not been found to correlate with the presence or severity of this entity. So, it has become partially obsolete. Realizing the need for non-invasive markers mirroring the presence of esophageal varices in order to reduce the number of endoscopy screening, we came back to determine whether there was a correlation between blood ammonia concentrations and the detection of portosystemic collateral veins, also evaluating splenomegaly, hypersplenism (thrombocytopenia and the severity of liver cirrhosis. Methods One hundred and fifty three consecutive patients with hepatic cirrhosis of various etiologies were recruited to participate in endoscopic and ultrasonography screening for the presence of portosystemic collaterals mostly esophageal varices, but also portal hypertensive gastropathy and large spontaneous shunts. Results Based on Child-Pugh classification, the median level of blood ammonia was 45 mcM/L in 64 patients belonging to class A, 66 mcM/L in 66 patients of class B and 108 mcM/L in 23 patients of class C respectively (p The grade of esophageal varices was concordant with venous ammonia levels (rho 0.43, p Conclusion Identifying cirrhotic patients with high blood ammonia concentrations could be clinically useful, as high levels would lead to suspicion of being in presence of collaterals, in clinical practice of esophageal varices, and pinpoint those patients requiring closer follow-up and endoscopic screening.

  19. The Cost of Collateralized Borrowing in the Colombian Money Market: Does Connectedness Matter?

    OpenAIRE

    Constanza Martínez; Carlos León

    2014-01-01

    Under the view that the market is a weighted and directed network (Barabási, 2003), this document is a first attempt to model the Colombian money market within a spatial econometrics framework. By estimating two standard spatial econometric models, we study the cost of collateralized borrowing (i.e. sell/buy backs) among Colombian financial institutions, and its relationship with the effects induced by traditional variables (leverage, size and borrowing levels), and by spatial variables resul...

  20. Treatment of Ischemic Apoplexy Based on the Theory of "Lingering Illness Affecting Collaterals"

    Institute of Scientific and Technical Information of China (English)

    Feng Lingmei; Sun Yan; Duan Shumin

    2007-01-01

    @@ Ischemic apoplexy, also called ischemic cerebrovascular disease (including cerebral thrombosis, cerebral embolism and transient cerebral ischemic attack), belongs to the TCM category of "wind-stroke syndrome". The increasingly high incidence of the disease has imposed serious influence on life quality of people. Based on the theory of "lingering illness affecting collaterals", we have treated the disease by acupuncture and oral administration of leech capsule and centipede capsule,with good therapeutic results reported as follows.

  1. Common polymorphisms of the peroxisome proliferator-activated receptor-gamma (Pro12Ala) and peroxisome proliferator-activated receptor-gamma coactivator-1 (Gly482Ser) and the response to pioglitazone in Chinese patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Hsieh, Ming-Chia; Lin, Kun-Der; Tien, Kai-Jen; Tu, Shih-Te; Hsiao, Jeng-Yueh; Chang, Shun-Jen; Lin, Shiu-Ru; Shing, Shih-Jang; Chen, Hung-Chun

    2010-08-01

    We investigated the effects of the common polymorphisms in the peroxisome proliferator-activated receptor-gamma (PPAR-gamma; Pro12Ala) and in PPAR-gamma coactivator-1(PGC-1; Gly482Ser) genes on the response to pioglitazone in Chinese with type 2 diabetes mellitus. A total of 250 patients with type 2 diabetes mellitus were treated with pioglitazone (30 mg/d) for 24 weeks without a change in previous medications. All patients were genotyped for the PPAR-gamma Pro12Ala and PGC-1 Gly482Ser polymorphisms. The Ala12Ala and Pro12Ala genotypes (26.0% vs 13.5%, P = .025) and Ala allele (15.6% vs 7.3%, P = .008) were significantly more frequent in pioglitazone responders than in nonresponders. The distribution of PGC-1 genotypes and alleles was not significantly different between responders and nonresponders. The decrease in fasting glucose (50.4 +/- 52.2 vs 43.3 +/- 51.7 mg/dL, P Pro12Ala and Ala12Ala) than in those without the allele (Pro12Pro). Baseline fasting glucose and triglyceride levels were related to the response of pioglitazone. Only the PPAR-gamma Pro12Ala polymorphism was found to be associated with the response of pioglitazone by multiple logistic regression analysis. The PPAR-gamma Pro12Ala gene polymorphism is associated with the response to pioglitazone in Chinese patients with type 2 diabetes mellitus. These findings may be helpful for targeted treatment of diabetes by identifying patients who are likely to respond to pioglitazone. Copyright 2010 Elsevier Inc. All rights reserved.

  2. Geraniol, alone and in combination with pioglitazone, ameliorates fructose-induced metabolic syndrome in rats via the modulation of both inflammatory and oxidative stress status.

    Directory of Open Access Journals (Sweden)

    Sherehan M Ibrahim

    Full Text Available Geraniol (GO potent antitumor and chemopreventive effects are attributed to its antioxidant and anti-inflammatory properties. In the current study, the potential efficacy of GO (250 mg/kg in ameliorating metabolic syndrome (MetS induced by fructose in drinking water was elucidated. Moreover, the effect of pioglitazone (5 and 10 mg/kg; PIO and the possible interaction of the co-treatment of GO with PIO5 were studied in the MetS model. After 4 weeks of treatment, GO and/or PIO reduced the fasting blood glucose and the glycemic excursion in the intraperitoneal glucose tolerance test. GO and PIO5/10 restrained visceral adiposity and partly the body weight gain. The decreased level of peroxisome proliferator activated receptor (PPAR-γ transcriptional activity in the visceral adipose tissue of MetS rats was increased by single treatment regimens. Though GO did not affect MetS-induced hyperinsulinemia, PIO5/10 lowered it. Additionally, GO and PIO5/10 suppressed glycated hemoglobin and the receptor for advanced glycated end products (RAGE. These single regimens also ameliorated hyperuricemia, the disrupted lipid profile, and the elevated systolic blood pressure evoked by MetS. The rise in serum transaminases, interleukin-1β, and tumor necrosis factor-α, as well as hepatic lipid peroxides and nitric oxide (NO was lowered by the single treatments to different extents. Moreover, hepatic non-protein thiols, as well as serum NO and adiponectin were enhanced by single regimens. Similar effects were reached by the combination of GO with PIO5; however, a potentiative interaction was noted on fasting serum insulin level, while synergistic effects were reflected as improved insulin sensitivity, as well as reduced RAGE and triglycerides. Therefore, GO via the transcriptional activation of PPAR-γ reduces inflammation and free radical injury produced by MetS. Thereby, these effects provide novel mechanistic insights on GO management of MetS associated critical

  3. The efficacy of methotrexate plus pioglitazone vs. methotrexate alone in the management of patients with plaque-type psoriasis: a single-blinded randomized controlled trial.

    Science.gov (United States)

    Lajevardi, Vahide; Hallaji, Zahra; Daklan, Soroush; Abedini, Robabeh; Goodarzi, Azadeh; Abdolreza, Mona

    2015-01-01

    Recently, thiazolidinediones have shown to be efficacious with a favorable safety profile when used in the treatment of chronic plaque-type psoriasis. The aim of this study was to evaluate and compare the efficacy and safety of a combination of methotrexate plus pioglitazone and methotrexate alone in plaque-type psoriasis. A total of 44 adult patients with plaque-type psoriasis were included in the study. Patients were randomized to treatment with methotrexate alone (group A) or methotrexate plus pioglitazone (group B) for 16 weeks. The primary efficacy outcome measure was psoriasis area and severity index (PASI) score change between the study groups at week 16 relative to baseline. The secondary efficacy outcome measure was dermatology life quality index (DLQI) score change between the two groups at week 16 relative to baseline. The PASI 75 score was also measured. After 16 weeks of therapy, the percentage of reduction in the mean PASI score was 70.3% in group B and 60.2% in group A. PASI 75 was achieved in 14 patients (63.6%) in group B compared with two patients (9.1%) in group A within 16 weeks, which was significant (P methotrexate in plaque-type psoriasis, as demonstrated by a reduction in the mean PASI scores. In terms of DLQI, there was no extra benefit by the addition of pioglitazone to methotrexate therapy.

  4. Effect of pioglitazone combined with cyproterone acetate on the reproductive hormone level and insulin resistance of patients with polycystic ovary syndrome

    Institute of Scientific and Technical Information of China (English)

    Hong-Wei Hao; Dong-Zhen Liu

    2015-01-01

    Objective: To analyze the effect of Pioglitazone combined with cyproterone acetate on the reproductive hormone level and insulin resistance of patients with polycystic ovary syndrome. Methods: 96 patients with the polycystic ovary syndrome in our hospital were randomly divided into observation group and controlgroup two groups, each of 48 cases. The control group was treated with the treatment of cyproterone acetate, observation group was treated with pioglitazone combined with cyproterone acetate treatment. The clinical efficacy of two groups were compared. The serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T) and fasting plasma glucose (FBG), fasting insulin (FINS) level before and after treatment and calculate the insulin resistance index (IR) were observed. Results: After treatment, serum FSH, LH and T levels of two groups were significantly lower than that before treatment (P0.05). FBG, FINS and IR of the patients in the observation group were significantly lower than the control group (P<0.05). Conclusion: pioglitazone combined with cyproterone acetate has significant therapeutic effect on polycystic ovary syndrome, can effectively improve the patients with insulin resistance and reproductive hormone disorder.

  5. Clinical effect of addition of beraprost sodium to pioglitazone treatment on the blood glucose levels in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Chen, T; Kusunoki, M; Sato, D; Tsutsui, H; Nakamura, T; Miyata, T; Oshida, Y

    2013-11-01

    In recent years, the number of patients with type 2 diabetes mellitus caused by insulin resistance has continued to increase in Japan. Insulin resistance is considered to be closely related to the risk of cardiovascular diseases and atherosclerotic diseases, represented by arteriosclerosis obliterans (ASO). Therefore, improvement of insulin resistance is one of the important strategies in the treatment of type 2 diabetes mellitus. At present, α-glucosidase inhibitors, incretin-related drugs, and thiazolidinediones are among the most important oral hypoglycemic drugs used to improve insulin resistance. In this study, the effect of beraprost sodium, a prostaglandin I2 derivative, in the treatment of type 2 diabetes mellitus was investigated. In type 2 diabetic patients with ASO who were under treatment with pioglitazone, additional treatment with beraprost sodium exerted a significant synergistic effect in reducing the serum HbA1c levels as compared to treatment with pioglitazone alone. This result indicates that concomitant administration of pioglitazone and beraprost sodium may be useful in the treatment of diabetes -mellitus.

  6. Efficacy and safety of pioglitazone added to alogliptin in Japanese patients with type 2 diabetes mellitus: a multicentre, randomized, double-blind, parallel-group, comparative study.

    Science.gov (United States)

    Kaku, K; Katou, M; Igeta, M; Ohira, T; Sano, H

    2015-12-01

    A phase IV, multicentre, randomized, double-blind, parallel-group, comparative study was conducted in Japanese subjects with type 2 diabetes mellitus (T2DM) who had inadequate glycaemic control, despite treatment with alogliptin in addition to diet and/or exercise therapy. Subjects with glycated haemoglobin (HbA1c) concentrations of 6.9-10.5% were randomized to receive 16 weeks' double-blind treatment with pioglitazone 15 mg, 30 mg once daily or placebo added to alogliptin 25 mg once daily. The primary endpoint was the change in HbA1c from baseline at the end of treatment period (week 16). Both pioglitazone 15 and 30 mg combination therapy resulted in a significantly greater reduction in HbA1c than alogliptin monotherapy [-0.80 and -0.90% vs 0.00% (the least squares mean using analysis of covariance model); p Pioglitazone/alogliptin combination therapy was effective and generally well tolerated in Japanese subjects with T2DM and is considered to be useful in clinical settings.

  7. Local control of information flow in segmental and ascending collaterals of single afferents.

    Science.gov (United States)

    Lomelí, J; Quevedo, J; Linares, P; Rudomin, P

    1998-10-08

    In the vertebrate spinal cord, the activation of GABA(gamma-amino-butyric acid)-releasing interneurons that synapse with intraspinal terminals of sensory fibres leading into the central nervous system (afferent fibres) produces primary afferent depolarization and presynaptic inhibition. It is not known to what extent these presynaptic mechanisms allow a selective control of information transmitted through specific sets of intraspinal branches of individual afferents. Here we study the local nature of the presynaptic control by measuring primary afferent depolarization simultaneously in two intraspinal collaterals of the same muscle spindle afferent. One of these collaterals ends at the L6-L7 segmental level in the intermediate nucleus, and the other ascends to segment L3 within Clarke's column, the site of origin of spinocerebellar neurons. Our results indicate that there are central mechanisms that are able to affect independently the synaptic effectiveness of segmental and ascending collaterals of individual muscle spindle afferents. Focal control of presynaptic inhibition thus allows the intraspinal branches of afferent fibres to function as a dynamic assembly that can be fractionated to convey information to selected neuronal targets. This may be a mechanism by which different spinal postsynaptic targets that are coupled by sensory input from a common source could be uncoupled.

  8. The relationship between mean platelet volume and coronary collateral vessels in patients with acute coronary syndromes

    Directory of Open Access Journals (Sweden)

    Gaurav Singhal

    2016-01-01

    Full Text Available Background: Elevated mean platelet volume (MPV has been proposed as a risk factor for coronary artery disease (CAD and is associated with poor clinical outcome in acute coronary syndrome (ACS. However, some studies have contradictory findings. Hence, we aimed to evaluate the association of MPV with the presence of coronary collateral vessel (CCV in patients with ACS. Objective: To find MPV value in ACS patients and to find the predictive value of MPV in the spectrum of CAD and to examine whether levels of MPV predict the presence of CCVs. Methods: A total of 180 patients with first ACS were included in the study. MPV was measured. All patients underwent coronary angiography to know disease severity and CCVs. The CCVs are graded according to the Rentrop scoring system and according to coronary angiography results; patients were divided into two groups as Group 1 (poor CCV and Group 2 (good CCV. Results: The MPV was 10.74 ± 2 fl in poor collateral group patients and 11.01 ± 1.7 fl in good collateral group (P = 0.421. The presence of CCV was not significantly associated with high levels of MPV. MPV value did not show any prediction of the spectrum of CAD. Conclusion: MPV on admission was not associated with the development of CCV positively in patients with ACS. Furthermore, it is not associated with a number of vessel involvements.

  9. Renovascular hypertension due to insufficient collateral flow in segmental artery occulusion

    Energy Technology Data Exchange (ETDEWEB)

    Park, Y. H.; Lee, S. Y.; Kim, S. H.; Sohn, H. S.; Chung, S. K. [College of Medicine, The Catholic Univ. of Korea, Seoul (Korea, Republic of)

    2001-07-01

    We report a case in which a 33-year-old woman with renovascular hypertension due to insufficient collateral flow in segmental renal artery occlusion demonstrated abnormality on captopril renal scintigram. Baseline renal scintigram with DTPA showed normal perfusion and excretion in left kidney and captopril renal scintigram with DTPA showed a focal area of decreased perfusion and delayed clearance in lower half of left kidney, suggesting segmental renal artery stenosis. Selective left renal arteriography showed complete obstruction in proximal portion of anterior segmental artery with multiple small collateral vessels from posterior segmental artery and capsular artery and delayed opacification in lower half of left kidney. These findings are suggestive of segmental hypoperfusion due to insufficient collateral blood flow resulting to positive captopril response. Patient's blood pressure have been controlled well with ACE (angiotensin converting enzyme) inhibitor and calcium channel blocker for 2 year. Follow-up baseline renal scintigram with MAG3 showed normal perfusion and excretion in left kidney and captopril renal scintigram with MAG3 showed a focal area of decreased perfusion and delayed clearance in lower lateral portion of left kidney, which was smaller size than that of previous renal scintigram. And captopril renal scintigram with DMSA demonstrated a small area of decreased DMSA uptake on this lesion compared to baseline DMSA scintigram.

  10. [Does ST-elevation in stress ECG depend on the extent of collateral circulation?].

    Science.gov (United States)

    Bettinger, R; Wendt, T; Klepzig, H; Kaltenbach, M

    1993-01-01

    As a possible cause of exercise-induced ST-elevation in patients without myocardial infarction, a poor or absent coronary circulation to the poststenotic coronary segment was postulated. To check this thesis, we examined 10 patients (pts.) with ST-elevation, respectively, ST-depression and comparable coronary status (coronary score 12 vs. 12; mean stenosis diameter 86 vs. 85%) and exercise parameters (work load 150 vs. 137.5 Watts; exercise duration 2.8 vs 3.5 min) with regard to their collateral circulation. In the group with ST-elevation there were nine pts. with severe proximal stenosis of the left anterior descending artery (LAD) and one pt. with a stenosis in the middle third of the right coronary artery. The 10 patients with ST-depression had a proximal stenosis in the LAD. The extent of the angiographically seen collaterals was equal in both groups. As a result, this study demonstrates that the size of the collateral circulation has no influence on the exercise-induced ST-elevation. The most plausible cause of exercise-induced ST-elevation is a functional decrease of the lumen of a severe stenosis.

  11. Is CT-based perfusion and collateral imaging sensitive to time since stroke onset?

    Directory of Open Access Journals (Sweden)

    Smriti eAgarwal

    2015-04-01

    Full Text Available Abstract PurposeCT-based perfusion and collateral imaging is increasingly used in the assessment of patients with acute stroke. Time of stroke onset is a critical factor in determining eligibility for and benefit from thrombolysis. Animal studies predict that the volume of ischemic penumbra decreases with time. Here we evaluate if CT is able to detect a relationship between perfusion or collateral status, as assessed by CT and time since stroke onset.Materials and MethodsWe studied fifty-three consecutive patients with proximal vessel occlusions, mean (SD age of 71.3 (14.9 years at a mean (SD of 125.2 (55.3 minutes from onset, using whole-brain CT perfusion (CTp imaging. Penumbra was defined using voxel-based thresholds for cerebral blood flow (CBF and mean transit time (MTT; core was defined by cerebral blood volume (CBV. Normalized penumbra fraction was calculated as Penumbra volume /(Penumbra volume +Core volume for both CBF and MTT (PenCBF and PenMTT, respectively. Collaterals were assessed on CT angiography (CTA. CTp ASPECTS score was applied visually, lower scores indicating larger lesions. ASPECTS ratios were calculated corresponding to penumbra fractions.ResultsBoth PenCBF and PenMTT showed decremental trends with increasing time since onset (Kendall’s tau-b=-0.196, p=0.055, and -0.187, p=0.068, respectively. The CBF/CBV ASPECTS ratio, which showed a relationship to PenCBF (Kendall’s tau-b=0.190, p=0.070, decreased with increasing time since onset (Kendall’s tau-b=-0.265, p=0.006. Collateral response did not relate to time (Kendall’s tau-b=-0.039, p=0.724.ConclusionEven within 4.5hrs since stroke onset, a decremental relationship between penumbra and time, but not between collateral status and time, may be detected using perfusion CT imaging. The trends that we demonstrate merit evaluation in larger datasets to confirm our results, which may have potential wider applications e.g. in the setting of strokes of unknown onset time.

  12. Pioglitazone enhances expression of genes involved in mitochondrial oxidative metabolism in skeletal muscle of women with polycystic ovary syndrome (PCOS)

    DEFF Research Database (Denmark)

    Skov, Vibe

    Aims                Polycystic ovary syndrome (PCOS) is a common endocrine disorder in premenopausal women and is associated with insulin resistance increasing the risk for developing type 2 diabetes mellitus. Studies have shown that thiazolidinediones (TZD) improve metabolic disturbances in PCOS...

  13. Vertebral body enhancement mimicking sclerotic osseous lesions in the setting of bilateral brachiocephalic vein thrombosis.

    Science.gov (United States)

    Berritto, Daniela; Abboud, Salim; Kosmas, Christos; Riherd, Daniel; Robbin, Mark

    2015-02-01

    Contrast enhancement of the vertebral body marrow may be seen secondary to collateral venous blood flow via the vertebral venous plexus in the setting of superior vena cava obstruction. We report a 48-year-old woman presenting with bilateral brachiocephalic vein obstruction and multilevel thoracic spine hyperdensities as seen on venous-phase CT angiography (CTA), initially concerning for sclerotic neoplastic lesions. A contrast-enhanced CT of the neck obtained 1 day prior to the chest CTA did not demonstrate any osseous abnormality, and inspection of the chest CTA demonstrated filling of perivertebral venous collateral vessels. The abnormal vertebral body enhancement was therefore feltsecondary to retrograde collateral venous flow via the basivertebral venous plexus in the setting of functional SVC obstruction. Vertebral body enhancement should be considered in patients with thoracic central venous obstruction when enhancement or apparent sclerosis of the vertebral bodies is seen on CTA.

  14. Anti-inflammatory effect of pioglitazone on insulin sensitivity and vascular endothelial cell function of patients with metabolic syndrome%吡格列酮抗炎作用对代谢综合征患者胰岛素敏感性、血管内皮细胞功能的影响

    Institute of Scientific and Technical Information of China (English)

    卢辉和; 黎叶飞; 盛臻强; 王毅

    2012-01-01

    目的 研究吡格列酮对伴糖耐量减低(IGT)的代谢综合征(MS)患者血管内皮细胞功能的影响.方法 对30例伴IGT的MS患者采用吡格列酮45 mg/d治疗8周.在治疗前后分别测定胰岛素敏感度检测指数(QU ICKI)、肱动脉内皮依赖性舒张功能(FMD)和硝酸甘油诱导的非内皮依赖性舒张功能(NID),高敏C反应蛋白(hs-CRP)改变.结果 治疗后FMD明显改善(P<0.01),QUICKI指数升高(P<0.05); hs-CRP水平降低(P<0.01).结论 吡格列酮能明显改善IGT的MS患者的血管内皮细胞功能,其机制可能与改善体内胰岛素抵抗,抑制慢性炎症反应有关.%Objective To explore the beneficial effects of pioglitazone on endothelial function in metabolic syndrome (MS) patients with impaired glucose tolerance (IGT). Methods Thirty MS patients with IGT were administrated pioglitazone (45 mg/d) for eight weeks. The quantitative insulin sensitivity check index (QUICKI), endotheliurrrdependent vasodilation (flow-mediated vasodilation, FMD) and endothelium-independent vasodilation (nitroglycerineinduced vasodilation, NID) were measured in the brachial artery by high resolution ultrasound technique were measured before and after treatment respectively. The changes of hsCRP were assessed as well. Results After treatment, the levels of FMD, QUICKI and hsCRP were improved significantly (P<0. 05, P<0. 01). Conclusion Pioglitazone treatment improves endothelial vasodilator function in MS patients via enhancing insulin sensitivity and inhibition of chronic inflammation.

  15. Lobeglitazone and pioglitazone as add-ons to metformin for patients with type 2 diabetes: a 24-week, multicentre, randomized, double-blind, parallel-group, active-controlled, phase III clinical trial with a 28-week extension.

    Science.gov (United States)

    Jin, S-M; Park, C-Y; Cho, Y M; Ku, B J; Ahn, C W; Cha, B-S; Min, K W; Sung, Y A; Baik, S H; Lee, K W; Yoon, K-H; Lee, M-K; Park, S W

    2015-06-01

    We aimed to compare the efficacy and safety of lobeglitazone and pioglitazone as add-ons to metformin in patients with type 2 diabetes. Patients who were inadequately controlled by metformin were randomized and treated once daily with either lobeglitazone (0.5 mg, n = 128) or pioglitazone (15 mg, n = 125) for 24 weeks, with a 28-week extension trial of lobeglitazone treatment in patients who consented. The primary endpoint was the change in glycated haemoglobin (HbA1c) concentration from baseline to week 24. At week 24, the mean change from baseline in HbA1c was -0.74% for the lobeglitazone group and -0.74% for the pioglitazone group, with a mean difference of 0.01% [95% confidence interval (CI) of difference, -0.16 to 0.18]. The effects of lobeglitazone on lipid variables and the adverse events associated with lobeglitazone were similar to those observed with pioglitazone. Lobeglitazone was not inferior to pioglitazone as an add-on to metformin in terms of their efficacy and safety.

  16. Research on the protection effect of pioglitazone for non-alcoholic fatty liver disease (NAFLD) in rats

    Institute of Scientific and Technical Information of China (English)

    XU Ping; ZHANG Xing-guo; LI You-ming; YU Chao-hui; XU Lei; XU Gen-yun

    2006-01-01

    Objective: The prevalence of non-alcoholic fatty liver disease (NAFLD) has markedly increased. Insulin resistance has been implicated in the pathogenesis of NAFLD. This study was aimed at observing the relationship between insulin resistance and NAFLD, and evaluating the role of pioglitazone (PGZ) acting as insulin-sensitizing agents in the prevention and treatment of rat fatty liver induced by high fat feeding. Methods: The rats were separated randomly into 6 groups: model group I were fed high simultaneous with high fat diet for 8 weeks after high fat feeding for 8 weeks, control group Ⅱ were fed normal food for 16 weeks.The rats were sacrificed after 8 weeks and 16 weeks respectively. Liver weight, body weight, serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), tumor necrosis factor alpha (TNL-α), fasting blood glucose (FBG), fasting plasma insulin (FINS), HOMA (homeostasis model assessment) insulin resistance index (HOMA-IR), and the liver histology of rats of all groups were assayed. Results: After 8 weeks, the liver in model group I showed typical steatosis, accompanied with mild to moderate lobular inflammatory cell infiltration, liver indexes and serum levels of ALT,AST, ALP, TNF-α were significantly increased (P<0.05) compared with control group I. Whereas, the degree of hepatic injury was attenuated in PGZ prevention group, liver indexes and serum levels of ALT, ALP were significantly decreased (P<0.05)compared with model group Ⅰ. After 16 weeks, notable steatosis, and lobular inflammation were observed in model group Ⅱ rat liver, while the degree of hepatic injury was attenuated in the PGZ treatment group. Liver index, serum levels of ALT, AST, ALP,FINS and HOMA-IR were significantly increased (P<0.05) in model group Ⅱ compared with control group Ⅱ. Whereas, in PGZ treatment group, serum levels of AST and FINS showed decreasing tendency, liver indexes, serum levels of ALT

  17. Variants of Rab GTPase-Effector Binding Protein-2 Cause Variation in the Collateral Circulation and Severity of Stroke.

    Science.gov (United States)

    Lucitti, Jennifer L; Sealock, Robert; Buckley, Brian K; Zhang, Hua; Xiao, Lin; Dudley, Andrew C; Faber, James E

    2016-12-01

    The extent (number and diameter) of collateral vessels varies widely and is a major determinant, along with arteriogenesis (collateral remodeling), of variation in severity of tissue injury after large artery occlusion. Differences in genetic background underlie the majority of the variation in collateral extent in mice, through alterations in collaterogenesis (embryonic collateral formation). In brain and other tissues, ≈80% of the variation in collateral extent among different mouse strains has been linked to a region on chromosome 7. We recently used congenic (CNG) fine mapping of C57BL/6 (B6, high extent) and BALB/cByJ (BC, low extent) mice to narrow the region to a 737 Kb locus, Dce1. Herein, we report the causal gene. We used additional CNG mapping and knockout mice to narrow the number of candidate genes. Subsequent inspection identified a nonsynonymous single nucleotide polymorphism between B6 and BC within Rabep2 (rs33080487). We then created B6 mice with the BC single nucleotide polymorphism at this locus plus 3 other lines for predicted alteration or knockout of Rabep2 using gene editing. The single amino acid change caused by rs33080487 accounted for the difference in collateral extent and infarct volume between B6 and BC mice attributable to Dce1. Mechanistically, variants of Rabep2 altered collaterogenesis during embryogenesis but had no effect on angiogenesis examined in vivo and in vitro. Rabep2 deficiency altered endosome trafficking known to be involved in VEGF-A→VEGFR2 signaling required for collaterogenesis. Naturally occurring variants of Rabep2 are major determinants of variation in collateral extent and stroke severity in mice. © 2016 American Heart Association, Inc.

  18. Studies on intracranial collateral circulation with multi-slice CT angiography in patients with symptomatic cerebral artery stenosis

    Directory of Open Access Journals (Sweden)

    Shu-qing ZHOU

    2011-06-01

    Full Text Available Objective To explore the features of intracranial collateral circulation in patients with symptomatic cerebral artery stenosis.Method Ninety-four patients with ischemic cerebrovascular disease admitted from Apr.2004 to Jun.2009 were involved in present study.All the patients were examined with cerebral multi-slice CT angiography,and the features of cerebral artery stenosis and intracranial collateral circulation were evaluated using maximum intensity projection(MIP and volume rendering(VR images of CT angiography.Result Of the 94 patients involved,48 were diagnosed as cerebral artery stenosis,including 29 cases of cerebral infarction,18 of transient ischemic attack(TIA and 1 of moyamoya disease(MMD.Among the 14 cases of severe cerebral artery stenosis or occlusion,cerebral infarction was found in 6 cases with lesser intracranial collateral vessels(including massive cerebral infarction in 4 cases and watershed infarction in 2 cases,and focal infarction of central semi-ovale in 1 case and TIA in 7 cases were found with abundant intracranial collateral vessels.Multiple lacunar infarction was found in 22 cases of mild or moderate cerebral artery stenosis,but there was no significant correlation between the stenosed arteries and infarction sites.Abundant intracranial collateral vessels were found in one patient with Moyamoya disease but no infarction was observed.Conclusions Intracranial collateral circulation plays an important role of compensation in patients with severe cerebral artery stenosis or occlusion.Cerebral angiography with multi-slice CT is of great significance in evaluation of cerebral artery stenosis and intracranial collateral circulation.

  19. Simple Atomic Absorption Spectroscopic and Spectrophotometric Methods for Determination of Pioglitazone Hydrochloride and Carvedilol in Pharmaceutical Dosage Forms

    Directory of Open Access Journals (Sweden)

    Afaf A. Abdelmonem

    2014-01-01

    Full Text Available This study represents simple atomic absorption spectroscopic and spectrophotometric methods for determination of pioglitazone hydrochloride (PGZ-HCl and carvedilol (CRV based on formation of ion-pair associates between drugs and inorganic complex, bismuth(III tetraiodide (Method A and between drugs and organic acidic dyes, fast green and orange G (Method B. Method A is based on formation of ion-pair associate between drugs and bismuth(III tetraiodide in acidic medium to form orange-red ion-pair associates, which can be quantitatively determined by two different procedures. The formed ion-pair associate is extracted by methylene chloride, dissolved in acetone, dried, and then decomposed by hydrochloric acid, and bismuth content is determined by direct atomic absorption spectrometric technique (Procedure 1 or extracted by methylene chloride, dissolved in acetone, and quantified spectrophotometrically at 490 nm (Procedure 2. Method B is based on formation of ion-pair associate between drugs and either fast green dye or orange G dye in acidic medium to form ion-pair associates. The formed ion-pair associate is extracted by methylene chloride and quantified spectrophotometrically at 630 nm (for fast green dye method or 498 nm (for orange G dye method. Optimal experimental conditions have been studied. Both methods are applied for determination of the drugs in tablets without interference.

  20. EFFECT OF PIOGLITAZONE ON HEPATIC ULTRA-STRUCTURE AND METABOLIC CHANGES INDUCED BY A HIGH SUCROSE DIET IN RATS

    Directory of Open Access Journals (Sweden)

    Mohamed D. Morsy

    2014-01-01

    Full Text Available Pioglitazone (Pio is a PPAR-γ agonist insulin sensitizer has anti-inflammatory activity. Our novel aspect was to investigate its hepatic anti-inflammatory activity at the level of ultra-structure and enzymatic changes in a high sucrose diet animal model. Forty male Sprague Dawley rats were divided into four equal groups: Control; control Pio; high sucrose diet; high sucrose diet Rio treated groups. Fourteen weeks later, serum glucose, insulin, lipogram, gamma glutamyle transferase, alanine transaminase, aspartate transaminase, alkaline phosphatase, fetuin-A and adiponectin levels were measured. Hepatic tissue homogenate levels of tumor necrosis factor-α, interleukin-6 and myeloperoxidase activity were determined. Microscopic and ultra-structure hepatic changes were conducted in all animal groups. Administration of Pio in HS+Pio group reduced significantly the hepatic inflammatory markers and the hepatic enzymes compared with HS group. Both light and electron microscopic examination revealed a great improvement of the hepatic tissue with Pio treatment. This study suggested that Pio treatment in obesity; in addition to insulin sensitizing activity; could protect the liver from the development of hepatic inflammation induced by a high sucrose diet not only at the enzymatic but also at ultra-structure levels.

  1. Local release of pioglitazone (a peroxisome proliferator-activated receptor γ agonist) accelerates proliferation and remodeling phases of wound healing.

    Science.gov (United States)

    Sakai, Shigeki; Sato, Keisuke; Tabata, Yasuhiko; Kishi, Kazuo

    2016-01-01

    Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily known for its anti-inflammatory and macrophage differentiation effects, as well as its ability to promote fat cell differentiation and reduce insulin resistance. Pioglitazone (Pio) is a PPARγ agonist used clinically as an anti-diabetic agent for improving insulin sensitivity in patients with diabetes. The objective of this study was to develop a drug delivery system (DDS) for the local release of Pio to promote wound healing. Pio of low aqueous solubility was water-solubilized by micelles formed from gelatin grafted with L-lactic acid oligomers, and incorporated into a biodegradable gelatin hydrogel. An 8-mm punch biopsy tool was used to prepare two skin wounds on either side of the midline of 8-week-old mice. Wounds were treated by the hydrogels with (Pio-hydrogel group) or without (control group) Pio, and the wound area were observed 1, 4, 7, and 14 days after treatment. In addition, a protein assay and immunohistological stain were performed to determine the effects of the Pio-hydrogel on inflammation and macrophage differentiation. The Pio-hydrogels promote wound healing. Moreover, Western blotting analysis demonstrated that treatment with Pio-hydrogels resulted in decreased levels of the cytokines MIP-2 and TGF-β, and increased levels of glucose-regulating adiponectin. It is concluded that Pio-incorporated hydrogels promote the proliferation and remodeling phases of wound healing, and may prove to be effective as wound dressings.

  2. The neuroprotective benefit from pioglitazone (PIO) addition on the alpha lipoic acid (ALA)-based treatment in experimental diabetic rats.

    Science.gov (United States)

    Jin, Heung Yong; Lee, Kyung Ae; Wu, Jin Zu; Baek, Hong Sun; Park, Tae Sun

    2014-12-01

    In this study, we investigated the combined effect of pioglitazone (PIO) with alpha lipoic acid (ALA) on the peripheral nerves of diabetic rats. Animals were divided into 8 groups (N = 6-8) and designated according to ALA (100 mg/kg/day) and PIO (10 mg/kg/day) treatment: Normal, Normal + ALA, Normal + PIO, Normal + ALA + PIO, DM, DM + ALA, DM + PIO, and DM + ALA + PIO. After 24 weeks, current perception threshold, mechanical allodynia, oxidative stresses, intraepidermal nerve fiber density (IENFD), and axonal morphology in the sciatic nerve were compared among groups. IENFD in the DM + ALA + PIO group was significantly less reduced than in other DM groups (7.61 ± 0.52 vs. 5.62 ± 0.96, 5.56 ± 0.60, and 7.10 ± 0.70 for DM, DM + ALA, and DM + PIO, respectively P diabetes. Moreover, PIO can be preferentially considered when additional glucose-lowering agent is required in DPN patients treated with ALA.

  3. Pioglitazone, a PPARγ agonist, inhibits growth and invasion of human hepatocellular carcinoma via blockade of the rage signaling.

    Science.gov (United States)

    Yang, Yuan; Zhao, Ling-Hao; Huang, Bo; Wang, Ruo-Yu; Yuan, Sheng-Xian; Tao, Qi-Fei; Xu, Yong; Sun, Han-Yong; Lin, Chuan; Zhou, Wei-Ping

    2015-12-01

    Pioglitazone (PGZ), a synthetic PPARγ ligand, is known to have anti-tumor activity. However, it is unclear how it acts against hepatocellular carcinoma (HCC). We hypothesized that the pathological receptor for advanced glycation end products (RAGE) is involved in the PGZ anti-tumor process. To test this notion, human primary HCC tissues and corresponding adjacent non-cancerous tissues (ANCT) from 75 consecutive cases were analyzed. The expression and clinical significance of RAGE was assessed by immunohistochemical assay through tissue microarray. After HCC cells were pretreated with different concentrations of PGZ, cell proliferation, apoptosis, cell invasion, and cell cycle distribution were evaluated by multiple assays. The results showed that, the positive expression of RAGE was significantly higher in HCC tissues than in ANCT (66.7% vs. 36.0%, P RAGE, NF-κB, HMGB1, p38MAPK, Ki-67, MMP-2, and CyclinD1. Furthermore, knockdown of RAGE or NF-κB by siRNA effectively suppressed cell proliferation and invasion, and mediated the inhibitory effects of PGZ in HCC cells. Taken together, our findings suggest that, RAGE is overexpressed in human HCC tissues, and is closely associated with the pathological staging and tumor invasion of HCC. In addition, PGZ as a PPARγ agonist may inhibit growth and invasion of HCC cells via blockade of the RAGE signaling. © 2014 Wiley Periodicals, Inc.

  4. MitoNEET Is a Uniquely Folded 2Fe-2S Outer Mitochondrial Membrane Protein Stabilized By Pioglitazone

    Energy Technology Data Exchange (ETDEWEB)

    Paddock, M.L.; Wiley, S.E.; Axelrod, H.L.; Cohen, A.E.; Roy, M.; Abresch, E.C.; Capraro, D.; Murphy, A.N.; Nechushtai, R.; Dixon, J.E.; Jennings, P.A.; /UC, San Diego /SLAC, SSRL /Hebrew U.

    2007-10-19

    Iron-sulfur (Fe-S) proteins are key players in vital processes involving energy homeostasis and metabolism from the simplest to most complex organisms. We report a 1.5 Angstrom x-ray crystal structure of the first identified outer mitochondrial membrane Fe-S protein, mitoNEET. Two protomers intertwine to form a unique dimeric structure that constitutes a new fold to not only the {approx}650 reported Fe-S protein structures but also to all known proteins. We name this motif the NEET fold. The protomers form a two-domain structure: a {beta}-cap domain and a cluster-binding domain that coordinates two acid-labile 2Fe-2S clusters. Binding of pioglitazone, an insulin-sensitizing thiazolidinedione used in the treatment of type 2 diabetes, stabilizes the protein against 2Fe-2S cluster release. The biophysical properties of mitoNEET suggest that it may participate in a redox-sensitive signaling and/or in Fe-S cluster transfer.

  5. A novel method to assess pial collateralization from stroke perfusion MRI: subdividing T{sub max} into anatomical compartments

    Energy Technology Data Exchange (ETDEWEB)

    Potreck, Arne; Seker, Fatih; Hoffmann, Angelika; Pfaff, Johannes; Bendszus, Martin; Heiland, Sabine; Pham, Mirko [Heidelberg University Hospital, Department of Neuroradiology, Heidelberg (Germany); Nagel, Simon [Heidelberg University Hospital, Department of Neurology, Heidelberg (Germany)

    2017-02-15

    To develop and validate a quantitative and observer-independent method to evaluate pial collateral circulation by DSC-perfusion MRI and test whether this novel method delivers diagnostic information which is redundant to or independent from conventional penumbra imaging by the mismatch approach. We retrospectively identified 47 patients with M1 occlusion who underwent MR diffusion/perfusion imaging and mechanical thrombectomy at our facility. By automated registration and segmentation, T{sub max} delays were attributed specifically to the pial, cortical and parenchymal compartments. The resulting pial volumes at delay were defined as the pial T{sub max} map-assessed collateral score (TMACS) and correlated with gold standard digital subtraction angiography (DSA). Mismatch ratio was assessed by conventional penumbra defining MRI criteria. Strong correlation was found between TMACS and angiographically assessed collateral score (Pearson ρ = -0.74, p < 0.001). In multiple logistic regression, both good collaterals according to TMACS [OR 4.3 (1.1-19, p = 0.04)] and mismatch ratio ≥ 3.5 [OR 12.3 (1.88-249, p = 0.03)] were independent predictors of favourable clinical outcome. Perfusion delay in the pial compartment, as evaluated by TMACS, closely reflects the extent of pial collaterals in gold-standard DSA. TMACS and mismatch ratio were found to be complementary predictors of a favourable clinical outcome, each adding independent predictive information. (orig.)

  6. Dynamic change of collateral flow varying with distribution of regional blood flow in acute ischemic rat cortex

    Science.gov (United States)

    Wang, Zhen; Luo, Weihua; Zhou, Fangyuan; Li, Pengcheng; Luo, Qingming

    2012-12-01

    Cerebral blood flow (CBF) is critical for the maintenance of cerebral function by guaranteed constant oxygen and glucose supply to brain. Collateral channels (CCs) are recruited to provide alternatives to CBF to ischemic regions once the primary vessel is occluded during ischemic stroke. However, the knowledge of the relationship between dynamic evolution of collateral flow and the distribution of regional blood flow remains limited. In this study, laser speckle imaging was used to assess dynamic changes of CCs and regional blood flow in a rat cortex with permanent middle cerebral artery occlusion (MCAo). We found that CCs immediately provided blood flow to ischemic territories after MCAo. More importantly, there were three kinds of dynamic changes of CCs during acute stroke: persistent CC, impermanent CC, and transient CC, respectively, related to different distributions of regional blood flow. Although there was the possible occurrence of peri-infarct depolarization (PID) during ischemia, there was no obvious significance about the onset time and duration of CCs between rats with and without PID. These results suggest that the initial arising of CCs does not ensure their persistence, and that collateral flow could be varied with distribution of regional blood flow in acute ischemic stroke, which may facilitate the understanding of collateral recruitment and promote the development of collateral therapeutics in the future.

  7. Infrared Thermal Imaging in Patients with Medial Collateral Ligament Injury of the Knee - A Retrospective Study

    Directory of Open Access Journals (Sweden)

    HyunJung Yang

    2014-12-01

    Full Text Available Objectives: Digital infrared thermographic imaging (DITI has been used widely for various inflammatory diseases, circulatory diseases, skin diseases, musculoskeletal diseases and cancers. In cases of ligament injury, obviously the temperature of the damaged area increases due to local inflammation; however, whether the temperature also increases due to DITI has not been determined. The purpose of the present study was to identify whether or not the changes of temperature in patient’s with medial collateral ligament injury were really due to infrared thermography and to determine the applicability of DITI for assessing ligament injuries. Methods: Twenty patient’s who underwent DITI for a medial collateral ligament injury from September 2012 to June 2014 were included in the current study. The thermographic images from the patient’s knees were divided to cover seven sub-areas: the middle of the patella, and the inferomedial, the inferolateral, the superomedial, the superolateral, the medial, and the lateral regions of patella. The temperatures of the seven regions were measured, and the temperature differences between affected and unaffected regions were analyzed by using the Wilcoxon signed rank test. Results: The 20 patient’s were composed of 14 women (70% and 6 men (30%, with a mean age of 62.15 ± 15.71 (mean ± standard deviation (SD years. The temperature of the affected side, which included the middle of the patella, and the inferomedial, the superomedial, the superolateral, and the medial regions, showed a significant increase compared to that of the unaffected side (P < 0.05. The inferolateral and the lateral regions showed no significant changes. Conclusion: Our study results suggest that DITI can show temperature changes if a patient has a ligament injury and that it can be applied in the evaluation of a medial collateral ligament injury.

  8. A Technique of Superficial Medial Collateral Ligament Reconstruction Using an Adjustable-Loop Suspensory Fixation Device.

    Science.gov (United States)

    Deo, Shaneel; Getgood, Alan

    2015-06-01

    This report describes superficial medial collateral ligament reconstruction of the knee using a novel method of graft fixation with the ACL Tightrope RT (Arthrex, Naples, FL). After tibial fixation with either a standard interference screw or staple, femoral fixation of the semitendinosus tendon is performed with the adjustable-loop suspensory fixation device, which allows for both initial graft tensioning and re-tensioning after cyclical knee range of motion. This provides the ability for the graft to accommodate for resultant soft-tissue creep and stress relaxation, thereby allowing for optimal soft-tissue tension and reduction in laxity at the end of the procedure.

  9. Lateral collateral ligament reconstruction for chronic varus instability of the hallux interphalangeal joint.

    Science.gov (United States)

    Cho, Jaeho

    2014-01-01

    Chronic varus instability of the hallux interphalangeal joint is a rare injury, and only a few reports of this injury have been published. In some studies, this injury has been related to taekwondo. Taekwondo is an essential martial art in the Korean military. We have described a case of varus instability of the hallux interphalangeal joint in a professional soldier who had practiced taekwondo for 5 years and the surgical outcome after reconstruction of the lateral collateral ligament with the fourth toe extensor tendon.

  10. Wikileaks: costruire la trasparenza - Analisi del video “Collateral Murder”

    Directory of Open Access Journals (Sweden)

    Isabella Pezzini

    2014-12-01

    Full Text Available L’articolo esamina la strategia comunicativa adottata da Wikileaks in occasione della diffusione del video “Collateral murder” (3 aprile 2010, in cui denunciava il comportamento dell’aviazione americana nella guerra in Iraq e si proponeva come un nuovo soggetto della controcomunicazione globale. Analizzando i modi in cui il video fu costruito a partire dalle registrazioni delle azioni militari sottratte agli stessi USA, emerge il rovesciamento narrativo che Wikileaks riuscì a ottenere, presentando la propria struttura come il vero Destinante custode dei valori condivisi dall’opinione pubblica mondiale, smascherando viceversa gli USA come Antidestinante.

  11. Surgical Management and Treatment of the Anterior Cruciate Ligament/Medial Collateral Ligament Injured Knee.

    Science.gov (United States)

    Dale, Kevin M; Bailey, James R; Moorman, Claude T

    2017-01-01

    The medial collateral ligament (MCL) is the most commonly injured ligament of the knee. The anterior cruciate ligament (ACL) is the most commonly injured ligament in conjunction with the MCL. Most MCL injuries can be treated nonoperatively, whereas the ACL often requires reconstruction. A good physical examination is essential for diagnosis, whereas radiographs and MRI of the knee confirm diagnosis and help guide treatment planning. Preoperative physical therapy should be completed before surgical management to allow for return of knee range of motion and an attempt at MCL healing.

  12. Collateral damage-free debridement using 193nm ArF laser

    Science.gov (United States)

    Wynne, James J.; Felsenstein, Jerome M.; Trzcinski, Robert; Zupanski-Nielsen, Donna; Connors, Daniel P.

    2011-03-01

    Burn eschar and other necrotic areas of the skin and soft tissue are anhydrous compared to the underlying viable tissue. A 193 nm ArF excimer laser, emitting electromagnetic radiation at 6.4 eV at fluence exceeding the ablation threshold, will debride such necrotic areas. Because such radiation is strongly absorbed by aqueous chloride ions through the nonthermal process of electron photodetachment, debridement will cease when hydrated (with chloride ions) viable tissue is exposed, avoiding collateral damage to this tissue. Such tissue will be sterile and ready for further treatment, such as a wound dressing and/or a skin graft.

  13. 64-row multidetector computed tomography portal venography of gastric variceal collateral circulation

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To study characteristics of collateral circulation of gastric varices (GVs) with 64-row multidetector computer tomography portal venography (MDCTPV).METHODS:64-row MDCTPV with a slice thickness of 0.625 mm and a scanning field from 2 cm above the tracheal bifurcation to the lower edge of the kidney was performed in 86 patients with GVS diagnosed by endoscopy. The computed tomography protocol included unenhanced,arterial and portal vein phases. The MDCTPV was performed on an AW4.3 workstation. GVs were c...

  14. Polymorphism of peroxisome proliferator-activated receptor γ (PPARγ) Pro12Ala in the Iranian population: relation with insulin resistance and response to treatment with pioglitazone in type 2 diabetes.

    Science.gov (United States)

    Namvaran, Fatemeh; Azarpira, Negar; Rahimi-Moghaddam, Parvaneh; Dabbaghmanesh, Mohammad Hossein

    2011-12-05

    The peroxisome proliferator-activated receptor γ (PPARγ) has important effects on insulin sensitivity, obesity and diabetes. Pioglitazone improves insulin sensitivity by activating PPARγ. In view of inter-individual variability in therapeutic response to pioglitazone, this study was designed to search for an association between type 2 diabetes mellitus and Pro12Ala single-nucleotide polymorphism (SNP) in PPARγ (SNP rs1801282) and to investigate whether these genetic variants affect pioglitazone response in an Iranian population. A total of 101 patients with type 2 diabetes were treated for 12 weeks with pioglitazone (15 mg/day). Paraclinical parameters were measured before and after therapy. We genotyped 128 control participants without diabetes and all patients with type 2 diabetes. The Pro12Ala polymorphism in PPARγ was detected with real-time PCR. The Ala allele was found in 7% of the control participants vs. 3% of those with type 2 diabetes (P=0.04). The genotypic frequencies of Pro/Ala were 14.06% in the former group vs. 5.94% in the latter (P=0.036). There were significant changes in some laboratory values and biochemical markers of insulin sensitivity after pioglitazone therapy. The Pro12Ala polymorphism was associated with significant changes in insulin-to-glucose ratio after treatment (P=0.015 and P=0.005). Our findings suggest that in carriers of the 12Ala variant, pioglitazone significantly reduced the risk of type 2 diabetes, and in diabetic patients with the Pro12Ala genotype, the therapeutic response to treatment was better than in patients with the Pro12Pro genotype, although the difference between groups did not reach statistical significance. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Collateral vessel presence in branch and central retinal vein occlusions and their impact on visual acuity and anatomical gains: a retrospective analysis.

    Science.gov (United States)

    Singh, Rishi P; Lee, Tamara J; Yau, Linda; Rubio, Roman G

    2014-11-01

    To evaluate the incidence of collateral vessel formation and to determine their impact on best-corrected visual acuity and central foveal thickness in patients with branch or central retinal vein occlusion (BRVO, CRVO) receiving 0.3 mg or 0.5 mg of ranibizumab, or sham. This retrospective analysis was performed in patients with macular edema secondary to retinal vein occlusion who received 6 monthly intravitreal injections of ranibizumab (0.3 mg or 0.5 mg), or sham, followed by 6 months of as-needed treatment. Collateral vessel presence, change from baseline best-corrected visual acuity, and change from baseline central foveal thickness were assessed at baseline and months 3, 6, 9, and 12. At month 12, 19.6% of BRVO patients receiving sham/0.5 mg and 16.7% receiving ranibizumab (0.3 mg and 0.5 mg pooled) manifested collaterals at the disk, whereas 48.2% and 47.2% displayed collaterals within the retina, respectively. In CRVO patients, 57.9% and 59.2% of all groups manifested collaterals on the disk, respectively, whereas 12.1% and 15.1% displayed collaterals within the retina. Mean best-corrected visual acuity gain in ranibizumab-treated BRVO and CRVO patients was similar, irrespective of collaterals within the retina ( P > 0.05; CRVO: P > 0.05). The location of collaterals differed between retinal vein occlusion subtypes and ranibizumab treatment did not affect collateral vessel incidence. The presence of collaterals did not seem to impact best-corrected visual acuity gains at month 12 in both BRVO and CRVO patients receiving ranibizumab, whereas generally greater central foveal thickness reductions were observed with presence of collaterals in BRVO patients.

  16. 二甲双胍配伍吡格列酮治疗2型糖尿病临床效果及安全性分析%Metformin Combined with Pioglitazone Treatment in Type 2 Diabetes Mellitus Clinical Efficacy and Safety Analysis

    Institute of Scientific and Technical Information of China (English)

    梁文杰

    2013-01-01

    Objective:To explore the combination of metformin pioglitazone treatment in type 2 diabetes:clinical efficacy and safety. Methods:100 cases of patients with type 2 diabetes were randomly divided into the observation group and the control group with 50 cases in each group, the observation group was treated with pioglitazone metformin treatment regimens, controls individually using metformin treatment, a total of16 weeks treatment. Treatment in the two groups were observed before and after fasting, postprandial glucose and insulin sensitivity in2h, adverse reactions and other indexes, comparing the two groups of clinical curative effect analysis of metformin, pioglitazone treatment in type 2diabetes mellitus with safety. Results: The observation group efficiency is 96%, the effective rate of control group was76%, between the two groups, the observation group was better than the control group, the difference was significant ( P0.05). Conclusion:Combined pioglitazone and metformin in treating type 2 diabetes mellitus, can effectively control FPG,2h postprandial plasma glucose, enhanced insulin sensitivity, improve insulin resistance, the effect is better than the single use of metformin, and the security is good.%  目的:探讨二甲双胍配伍吡格列酮治疗2型糖尿病临床效果及其安全性。方法:将我院100例2型糖尿病患者随机分为观察组和对照组各50例,观察组采用二甲双胍配伍吡格列酮治疗方案,对照组单独使用二甲双胍治疗,共治疗16周。观察两组治疗前后空腹、餐后2h血糖及胰岛素敏感性、不良反应等指标,对比两组临床疗效,分析二甲双胍配伍吡格列酮治疗2型糖尿病的安全性。结果:观察组有效率为96.0%,对照组有效率为76.0%,两组疗效对比,观察组明显优于对照组,差异具有显著性(P0.05)。结论:吡格列酮联合二甲双胍治疗2型糖尿病,能有效地控制FPG、餐后2h血糖水平,增强胰

  17. Effects of pioglitazone on the expression of AdipoR mRNA of aorta in hyperlipidemia rats%吡格列酮对高脂血症大鼠主动脉脂联素受体mRNA表达的影响

    Institute of Scientific and Technical Information of China (English)

    徐玉顺; 沈思钰; 蔡辉

    2012-01-01

    ), and the serum APN in Pio group was obviously increased (P<0. 05). Treatment with pioglitazone enhanced the mRNA expression of both AdipoRl and AdipoR2(P<0. 05 or P<0. 01). Conclusions Decreased expression of AdipoR may involve in vascular impairment in rats with high-fat diet induced hyperlipidemia. Pioglitazone may exerte a significant vascular protective effect in hyperlipidemia rats, which may relate to increased serum APN and expression of AdipoR in vascular wall and contribute to their anti-atherosclerosis effect.

  18. Coronary collaterals

    NARCIS (Netherlands)

    Koerselman, Jeroen

    2004-01-01

    Cardiovascular diseases, in particular coronary artery disease, are the leading cause of death and disease in industrialized countries. Atherosclerotic changes of the arterial vessel wall constitute one of the major causes for the occurrence of cardiovascular disease. Important risk factors for

  19. Coronary collaterals

    NARCIS (Netherlands)

    Koerselman, Jeroen

    2004-01-01

    Cardiovascular diseases, in particular coronary artery disease, are the leading cause of death and disease in industrialized countries. Atherosclerotic changes of the arterial vessel wall constitute one of the major causes for the occurrence of cardiovascular disease. Important risk factors for card

  20. Cardiovascular safety of rosiglitazone and pioglitazone%罗格列酮和吡格列酮的心血管安全性

    Institute of Scientific and Technical Information of China (English)

    卢宇; 马德琳; 余学锋

    2015-01-01

    Rosiglitazone and pioglitazone belong to thiazolidinediones( TZD)insulin sensitizers, mainly used for the treatment of type 2 diabetes. Rosiglitazone was restricted to use or withdrawn from the market due to possibly increased cardiovascular events in 2010,and then was released for insufficient evidence in 2013. The large prospective clinical trial and Meta-analysis indicated that pioglitazone has cardiovascular protective effect,since the drug reduced risk of myocardial infarction/stroke/death of patients with type 2 diabetes. The different cardiovascular risk of rosiglitazone and pioglitazone maybe related to the differences in effect on lipid metabolism or in gene regulation.%罗格列酮和吡格列酮同属为噻唑烷二酮类胰岛素增敏剂,主要用于2型糖尿病的治疗。罗格列酮因可能增加心血管事件风险于2010年被限用(美国)或禁用(欧洲),2013年又因增加心血管事件风险证据不足被解禁。吡格列酮上市后的大型前瞻性临床研究和Meta分析结果显示,该药可以使2型糖尿病患者心肌梗死/中风/死亡的风险降低,从而被认为有心血管保护作用。罗格列酮和吡格列酮心血管风险的差异,可能与它们对2型糖尿病患者脂代谢影响的不同有关,也可能与其基因调控的不同有关。

  1. Chemoembolization of Extrahepatic Collateral Arteries for Treatment of Hepatocellular Carcinoma in the Caudate Lobe of the Liver

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Sungmin; Kim, Hyo-Cheol, E-mail: angiointervention@gmail.com; Chung, Jin Wook; Jung, Hyun-Seok; Hur, Saebeom; Lee, Myungsu; Jae, Hwan Jun [Seoul National University Hospital, Department of Radiology, Seoul National University College of Medicine, Institute of Radiation Medicine, Seoul National University Medical Research Center, and Clinical Research Institute (Korea, Republic of)

    2015-04-15

    PurposeThis study was designed to evaluate the efficacy and safety in performing chemoembolization of extrahepatic collateral arteries (EHC) for hepatocellular carcinoma (HCC) located in the caudate lobe.MethodsBetween January 2006 and November 2013, chemoembolization via EHC was performed in 35 patients with 35 caudate HCCs. Preprocedural and follow-up CT or MR scans, angiographic images, and medical records were reviewed retrospectively in consensus. Chi-square analysis was used to evaluate the relationship between tumor characteristics and type of EHC and that between tumor response and the characteristics of the tumor and chemoembolization.ResultsIn 31 (88.6 %) patients, EHCs supplying the caudate HCC originated from the right inferior phrenic artery (RIPA). The remaining four HCCs were supplied by the gastroduodenal artery, dorsal pancreatic artery, and right and left gastric arteries. Superselective catheterization of tumor-feeding vessels from the EHC was achieved in 27 patients (77.1 %). There were no major complications. Individual tumor response supplied by the EHC at follow-up contrast-enhanced CT were as follows: complete response (n = 18), partial response (n = 9), stable disease (n = 3), and progressive disease (n = 3). Non-RIPA EHCs were significantly more common in patients who had previously received chemoembolization via the RIPA (50 %) than those who had not (6.5 %; P = 0.01). There was no significant predictive factor associated with tumor response.ConclusionsHCC in the caudate lobe can be supplied by several EHCs. Chemoembolization via these arteries can be performed safely and effectively.

  2. Asymmetric varus and valgus stability of the anatomic cadaver knee and the load sharing between collateral ligaments and bearing surfaces.

    Science.gov (United States)

    Wang, Xiaonan; Malik, Aamer; Bartel, Donald L; Wickiewicz, Thomas L; Wright, Timothy

    2014-08-01

    Knee joint stability is important in maintaining normal joint motion during activities of daily living. Joint instability not only disrupts normal motion but also plays a crucial role in the initiation and progression of osteoarthritis. Our goal was to examine knee joint coronal plane stability under varus or valgus loading and to understand the relative contributions of the mechanisms that act to stabilize the knee in response to varus-valgus moments, namely, load distribution between the medial and lateral condyles and the ligaments. A robot testing system was used to determine joint stability in human cadaveric knees as described by the moment versus angular rotation behavior under varus and valgus loads at extension and at 30 deg and 90 deg of flexion. The anatomic knee joint was more stable in response to valgus than varus moments, and stability decreased with flexion angle. The primary mechanism for providing varus-valgus stability was the redistribution of the contact force on the articular surfaces from both condyles to a single condyle. Stretching of the collateral ligaments provided a secondary stabilizing mechanism after the lift-off of a condyle occurred. Compressive loads applied across the knee joint, such as would occur with the application of muscle forces, enhanced the ability of the articular surface to provide varus-valgus moment, and thus, helped stabilize the joint in the coronal plane. Coupled internal/external rotations and anteroposterior and medial-lateral translations were variable and in the case of the rotations were often as large as the varus-valgus rotations created by the applied moment.

  3. Aortopulmonary collateral flow is related to pulmonary artery size and affects ventricular dimensions in patients after the fontan procedure.

    Directory of Open Access Journals (Sweden)

    Heiner Latus

    Full Text Available BACKGROUND: Aortopulmonary collaterals (APCs are frequently found in patients with a single-ventricle (SV circulation. However, knowledge about the clinical significance of the systemic-to-pulmonary shunt flow in patients after the modified Fontan procedure and its potential causes is limited. Accordingly, the aim of our study was to detect and quantify APC flow using cardiovascular magnetic resonance (CMR and assess its impact on SV volume and function as well as to evaluate the role of the size of the pulmonary arteries in regard to the development of APCs. METHODS: 60 patients (mean age 13.3 ± 6.8 years after the Fontan procedure without patent tunnel fenestration underwent CMR as part of their routine clinical assessment that included ventricular functional analysis and flow measurements in the inferior vena cava (IVC, superior vena cava (SVC and ascending aorta (Ao. APC flow was quantified using the systemic flow estimator: (Ao - (IVC + SVC. Pulmonary artery index (Nakata index was calculated as RPA + LPA area/body surface area using contrast enhanced MR angiography. The patient cohort was divided into two groups according to the median APC flow: group 1 0.495 l/min/m(2. RESULTS: Group 1 patients had significant smaller SV enddiastolic (71 ± 16 vs 87 ± 25 ml/m(2; p=0.004 and endsystolic volumes (29 ± 11 vs 40 ± 21 ml/m(2; p=0.02 whereas ejection fraction (59 ± 9 vs 56 ± 13%; p=0.38 differed not significantly. Interestingly, pulmonary artery size showed a significant inverse correlation with APC flow (r=-0.50, p=0.002. CONCLUSIONS: Volume load due to APC flow in Fontan patients affected SV dimensions, but did not result in an impairment of SV function. APC flow was related to small pulmonary artery size, suggesting that small pulmonary arteries represent a potential stimulus for the development of APCs.

  4. 吡格列酮对大鼠脑出血后脑组织细胞凋亡及自由基水平的影响%Effects of Pioglitazone on Cell Apoptosis and Free Radical Levels in Brain Tissue of Rats withIntracerebral Hemorrhage

    Institute of Scientific and Technical Information of China (English)

    韩宁; 吴丹红; 黄菲菲; 孙姬

    2012-01-01

    Aim: To investigate the protective effect of pioglitazone on intracerebral hemorrhage in rats and its possible mechanism. Methods: A total of 72 male SD rats were divided randomly into six groups. Intervention group 1 (n=12): Pioglitazone peroxisome proliferator-activated receptor gamma(PPAR7 activator) were gastrically administrated 6 h before modeling, and the original dosages were maintained after modeling. Intervention group 2 (n=12): Pioglitazone were gastrically administrated 6 h before modeling, and were withdrawn after modeling. Intervention group 3 (n=12): The drugs were not given before modeling, and were gastrically administrated after modeling. Model group 4 (n=12): The drags were not given before and after modeling. Sham operation group (n=12): The rats were performed with needling insertion without injection. Normal group (n=12) was set up. The dose of gastrically administrated pioglitazone was 15 mg·kg-1d-1. Rats in each group were sacrificed at 72 h after operation. Biochemical detection of the superoxide dismutase (SOD) and malondialdehyde (MDA) concentration of brain tissue were performed. The Western blot was used to determine the PPARy and caspase-3 protein expression in brain tissue. HE and TUNEL staining were used to observe the brain edema and apoptosis respectively. Results: PPARy activator pioglitazone could significantly reduce the extent of brain edema and inflammatory cell infiltration of the brain tissue in rats at 72 h after cerebral hemorrhage, as well as reduce the number of apoptotic cells in brain tissue, and enhance the SOD activity and increase the expression of PPARy, and caspase-3 protein in brain tissue, and inhibit the MDA levels. The effect of prophylactic administration of piogiitazone before cerebral hemorrhage was better than that of the treatment after hemorrhage. Conclusion: PPARy activator pioglitazone can relieve the hemorrhagic brain injury in the rat brain, and protect the brain, possibly by increasing the PPARy

  5. Corruption of coronary collateral growth in metabolic syndrome: Role of oxidative stress.

    Science.gov (United States)

    Pung, Yuh Fen; Chilian, William M

    2010-12-26

    The myocardium adapts to ischemic insults in a variety of ways. One adaptation is the phenomenon of acute preconditioning, which can greatly ameliorate ischemic damage. However, this effect wanes within a few hours and does not confer chronic protection. A more chronic adaptation is the so-called second window of preconditioning, which enables protection for a few days. The most potent adaptation invoked by the myocardium to minimize the effects of ischemia is the growth of blood vessels in the heart, angiogenesis and arteriogenesis (collateral growth), which prevent the development of ischemia by enabling flow to a jeopardized region of the heart. This brief review examines the mechanisms underlying angiogenesis and arteriogenesis in the heart. The concept of a redox window, which is an optimal redox state for vascular growth, is discussed along with signaling mechanisms invoked by reactive oxygen species that are stimulated during ischemia-reperfusion. Finally, the review discusses of some of the pathologies, especially the metabolic syndrome, that negatively affect collateral growth through the corruption of redox signaling processes.

  6. Medial collateral ligament knee sprains in college football. Brace wear preferences and injury risk.

    Science.gov (United States)

    Albright, J P; Powell, J W; Smith, W; Martindale, A; Crowley, E; Monroe, J; Miller, R; Connolly, J; Hill, B A; Miller, D

    1994-01-01

    In this prospective, multiinstitutional analysis of medial collateral ligament sprains in college football players, we categorized 987 previously uninjured study subjects according to frequency of wearing preventive knee braces, studied the patterns by which 47 of 100 injuries occurred to unbraced knees, and identified several extrinsic, sport-specific risk factors shared for both braced and unbraced knees. The attendance, brace wear choice, position, string, and session of each participant were recorded daily; medial collateral ligament sprains were reported whenever tissue damage was confirmed. Both the likelihood of wearing braces and risk of injury without them was highly dependent on session (games/practices), position group (line, linebacker/tight end, skill), and string group (players/nonplayers). Subjects wearing braces often faced a high injury risk to their unbraced knees, a finding compatible with the opinion that braces were a necessary evil, best worn when concern over danger of injury outweighed desire for speed and agility. It is concluded that to avoid misinterpretations due to the confounding influence of brace wear selection bias, accurate investigation of daily brace wear patterns is required. Then, before considing the impact of preventive knee braces, a repartitioning of the data base is essential to assure that only similar groups will be compared.

  7. Corruption of coronary collateral growth in metabolic syndrome: Role of oxidative stress

    Science.gov (United States)

    Pung, Yuh Fen; Chilian, William M

    2010-01-01

    The myocardium adapts to ischemic insults in a variety of ways. One adaptation is the phenomenon of acute preconditioning, which can greatly ameliorate ischemic damage. However, this effect wanes within a few hours and does not confer chronic protection. A more chronic adaptation is the so-called second window of preconditioning, which enables protection for a few days. The most potent adaptation invoked by the myocardium to minimize the effects of ischemia is the growth of blood vessels in the heart, angiogenesis and arteriogenesis (collateral growth), which prevent the development of ischemia by enabling flow to a jeopardized region of the heart. This brief review examines the mechanisms underlying angiogenesis and arteriogenesis in the heart. The concept of a redox window, which is an optimal redox state for vascular growth, is discussed along with signaling mechanisms invoked by reactive oxygen species that are stimulated during ischemia-reperfusion. Finally, the review discusses of some of the pathologies, especially the metabolic syndrome, that negatively affect collateral growth through the corruption of redox signaling processes. PMID:21191543

  8. Splenic artery aneurysm: a diagnostic challenge in the setting of extensive portal venous collaterals

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, Grace S.; Vo, Nghia J.; Ishak, Gisele E.; Swanson, Jonathan O.; Otto, Randolph K. [University of Washington, Seattle Children' s Hospital, Department of Radiology, Seattle, WA (United States)

    2010-07-15

    We present a 16-year-old boy with autoimmune liver disease and longstanding portal hypertension in whom a CT arteriogram demonstrated a large aneurysm arising from the distal, extra-parenchymal portion of the splenic artery. Because of its location adjacent to multiple venous collaterals, the aneurysm was indistinguishable from splenic varices on initial imaging with Doppler sonography and on portal venous-phase CT. There is an increased risk of rupture of splenic artery aneurysms in the post-liver transplant period, with high associated mortality, and therefore diagnosis of splenic artery aneurysm prior to liver transplantation is clinically important. It is quite possible that the diagnosis of splenic artery aneurysm in this case would have been missed in the absence of dedicated arterial-phase imaging. As radiologists strive to reduce radiation exposure in children, this case highlights a potential diagnostic pitfall of both Doppler sonography and venous or single-acquisition arterial/venous-phase CT angiogram in children with venous collaterals and an undiagnosed splenic artery aneurysm. (orig.)

  9. Transcriptional changes in sensory ganglia associated with primary afferent axon collateral sprouting in spared dermatome model

    Directory of Open Access Journals (Sweden)

    Benjamin J. Harrison

    2015-12-01

    Full Text Available Primary afferent collateral sprouting is a process whereby non-injured primary afferent neurons respond to some stimulus and extend new branches from existing axons. Neurons of both the central and peripheral nervous systems undergo this process, which contributes to both adaptive and maladaptive plasticity (e.g., [1–9]. In the model used here (the “spared dermatome” model, the intact sensory neurons respond to the denervation of adjacent areas of skin by sprouting new axon branches into that adjacent denervated territory. Investigations of gene expression changes associated with collateral sprouting can provide a better understanding of the molecular mechanisms controlling this process. Consequently, it can be used to develop treatments to promote functional recovery for spinal cord injury and other similar conditions. This report includes raw gene expression data files from microarray experiments in order to study the gene regulation in spared sensory ganglia in the initiation (7 days and maintenance (14 days phases of the spared dermatome model relative to intact (“naïve” sensory ganglia. Data has been deposited into GEO (GSE72551.

  10. Myeloperoxidase targets oxidative host attacks to Salmonella and prevents collateral tissue damage.

    Science.gov (United States)

    Schürmann, Nura; Forrer, Pascal; Casse, Olivier; Li, Jiagui; Felmy, Boas; Burgener, Anne-Valérie; Ehrenfeuchter, Nikolaus; Hardt, Wolf-Dietrich; Recher, Mike; Hess, Christoph; Tschan-Plessl, Astrid; Khanna, Nina; Bumann, Dirk

    2017-01-23

    Host control of infections crucially depends on the capability to kill pathogens with reactive oxygen species (ROS). However, these toxic molecules can also readily damage host components and cause severe immunopathology. Here, we show that neutrophils use their most abundant granule protein, myeloperoxidase, to target ROS specifically to pathogens while minimizing collateral tissue damage. A computational model predicted that myeloperoxidase efficiently scavenges diffusible H2O2 at the surface of phagosomal Salmonella and converts it into highly reactive HOCl (bleach), which rapidly damages biomolecules within a radius of less than 0.1 μm. Myeloperoxidase-deficient neutrophils were predicted to accumulate large quantities of H2O2 that still effectively kill Salmonella, but most H2O2 would leak from the phagosome. Salmonella stimulation of neutrophils from normal and myeloperoxidase-deficient human donors experimentally confirmed an inverse relationship between myeloperoxidase activity and extracellular H2O2 release. Myeloperoxidase-deficient mice infected with Salmonella had elevated hydrogen peroxide tissue levels and exacerbated oxidative damage of host lipids and DNA, despite almost normal Salmonella control. These data show that myeloperoxidase has a major function in mitigating collateral tissue damage during antimicrobial oxidative bursts, by converting diffusible long-lived H2O2 into highly reactive, microbicidal and locally confined HOCl at pathogen surfaces.

  11. Comparative evaluation of effects of combined oral anti-diabetic drugs (sulfonylurea plus pioglitazone and sulfonylurea plus metformin over lipid parameters in type 2 diabetic patients

    Directory of Open Access Journals (Sweden)

    Sukanta Sen

    2013-06-01

    Full Text Available Background: Type 2 diabetes is as