Identification of Dipeptidyl-Peptidase (DPP)5 and DPP7 in Porphyromonas endodontalis, Distinct from Those in Porphyromonas gingivalis.

Science.gov (United States)

Nishimata, Haruka; Ohara-Nemoto, Yuko; Baba, Tomomi T; Hoshino, Tomonori; Fujiwara, Taku; Shimoyama, Yu; Kimura, Shigenobu; Nemoto, Takayuki K

2014-01-01

Dipeptidyl peptidases (DPPs) that liberate dipeptides from the N-terminal end of oligopeptides are crucial for the growth of Porphyromonas species, anaerobic asaccharolytic gram negative rods that utilize amino acids as energy sources. Porphyromonas endodontalis is a causative agent of periapical lesions with acute symptoms and Asp/Glu-specific DPP11 has been solely characterized in this organism. In this study, we identified and characterized two P. endodontalis DPPs, DPP5 and DPP7. Cell-associated DPP activity toward Lys-Ala-4-methylcoumaryl-7-amide (MCA) was prominent in P. endodontalis ATCC 35406 as compared with the Porphyromonas gingivalis strains ATCC 33277, 16-1, HW24D1, ATCC 49417, W83, W50, and HNA99. The level of hydrolysis of Leu-Asp-MCA by DPP11, Gly-Pro-MCA by DPP4, and Met-Leu-MCA was also higher than in the P. gingivalis strains. MER236725 and MER278904 are P. endodontalis proteins belong to the S9- and S46-family peptidases, respectively. Recombinant MER236725 exhibited enzymatic properties including substrate specificity, and salt- and pH-dependence similar to P. gingivalis DPP5 belonging to the S9 family. However, the kcat/Km figure (194 µM-1·sec-1) for the most potent substrate (Lys-Ala-MCA) was 18.4-fold higher as compared to the P. gingivalis entity (10.5 µM-1·sec-1). In addition, P. endodontalis DPP5 mRNA and protein contents were increased several fold as compared with those in P. gingivalis. Recombinant MER278904 preferentially hydrolyzed Met-Leu-MCA and exhibited a substrate specificity similar to P. gingivalis DPP7 belonging to the S46 family. In accord with the deduced molecular mass of 818 amino acids, a 105-kDa band was immunologically detected, indicating that P. endodontalis DPP7 is an exceptionally large molecule in the DPP7/DPP11/S46 peptidase family. The enhancement of four DPP activities was conclusively demonstrated in P. endodontalis, and remarkable Lys-Ala-MCA-hydrolysis was achieved by qualitative and quantitative

Novel combination treatment of type 2 diabetes DPP-4 inhibition + metformin

Directory of Open Access Journals (Sweden)

Bo Ahrén

2008-04-01

Full Text Available Bo AhrénDepartment of Clinical Sciences, Division of Medicine, Lund University, Lund, SwedenAbstract: Inhibition of dipeptidyl peptidase-4 (DPP-4 as a novel therapy for type 2 diabetes is based on prevention of the inactivation process of bioactive peptides, the most important in the context of treatment of diabetes of which is glucagon-like peptide-1 (GLP-1. Most clinical experience with DPP-4 inhibition is based on vildagliptin (GalvusR, Novartis and sitagliptin (JanuviaR, Merck. These compounds improve glycemic control both in monotherapy and in combination with other oral hyperglycemic agents. Both have also been shown to efficiently improve glycemic control when added to ongoing metformin therapy in patients with inadequate glycemic control. Under that condition, they reduce HbA1c levels by 0.65%–1.1% (baseline HbA1c 7.2–8.7% in studies up to 52 weeks of duration in combination versus continuous therapy with metformin alone. Sitagliptin has also been examined in initial combination therapy with metformin have; HbA1c was reduced by this combination by 2.1% (baseline HbA1c 8.8% after 24 weeks of treatment. Both fasting and prandial glucose are reduced by DPP-4 inhibition in combination with metformin in association with improvement of insulin secretion and insulin resistance and increase in concentrations of active GLP-1. The combination of DPP-4 inhibition and metformin has been shown to be highly tolerable with very low risk of hypoglycemia. Hence, DPP-4 inhibition in combination with metformin is an efficient, safe and tolerable combination therapy for type 2 diabetes.Keywords: DPP-4 inhibition, sitagliptin, vildagliptin, metformin, type 2 diabetes

Reversible reduction of nevirapine plasma concentrations during rifampicin treatment in patients coinfected with HIV-1 and tuberculosis.

Science.gov (United States)

Matteelli, Alberto; Saleri, Nuccia; Villani, Paola; Bonkoungou, Victor; Carvalho, Anna Cristina C; Kouanda, Seni; Sanou, Marie J; Simporé, Jacques; Monno, Laura; Carosi, Giampiero; Regazzi, Mario; Dembele, Mathurin

2009-09-01

Nevirapine (NVP) plasma levels are reduced in patients receiving rifampicin (RFM) for tuberculosis (TB) treatment. We determined variations over time of the pharmacokinetic parameters of NVP in patients who receive RFM. HIV-1-infected patients with CD4+ T-lymphocyte count NVP. Full NVP pharmacokinetic curves were calculated at 4 (T1) and 10 weeks (T2) of combined therapy and at 4 (T3) and 26 weeks after termination of anti-TB therapy. In 16 enrolled subjects, the median value of the area under the curve of NVP was reduced by 25.6% at T1 compared with NVP alone (43.7 vs. 58.7 microg x mL(-1) x h(-1); P = 0.02). The reduction was only 7.5% at T2 (54.3 vs. 58.7 microg x mL(-1) x h(-1); P = 0.17). The median C trough was reduced of 19.5% at T1 compared with T3 (3.3 vs. 4.2 microg/mL; P = 0.02) and of 7.1% at T2 compared with T3 (3.9 vs. 4.2 microg/mL; P = 0.17). The proportion of subjects with C trough values NVP during concomitant RFM treatment substantially decreases over time.

Stimulation of intestinal growth and function with DPP-IV inhibition in a mouse short bowel syndrome model

DEFF Research Database (Denmark)

Sueyoshi, Ryo; Ignatoski, Kathleen M Woods; Okawada, Manabu

2014-01-01

, and 7 days followed by 23 days washout period. Adaptive response was assessed by morphology, intestinal epithelial cell (IEC) proliferation (PCNA), epithelial barrier function (transepithelial resistance), RT-PCR for intestinal transport proteins, GLP-2R, and IGF-1R, and GLP-2 plasma levels. Glucose-stimulated...... sodium transport was assessed for intestinal absorptive function. Seven days of DPP4-I treatment facilitated an increase in GLP-2R levels, intestinal growth, and IEC proliferation. Treatment led to differential effects over time with greater absorptive function early, and enhanced proliferation at later...... time points. Interestingly, 7 day treatment followed by 23 days of non-treatment showed continued adaptation. DPP-IV-I enhanced IEC proliferative action up to 90-days post-resection, but this action seemed to peak by 30 days, as did GLP-2 plasma levels. Thus, use of DPP4-I treatment may prove...

Trust No. 728 FIPATERM; Fideicomiso No. 728 FIPATERM

Energy Technology Data Exchange (ETDEWEB)

Comision Federal de Electricidad (CFE)

2005-07-01

The FIPATERM is an agency of the Administracion Publica Paraestatal, created to administer economic resources destined to programs or projects benefiting the economy or the social welfare of the country. It is a legally constituted trust and it has the aim, among others, of developing support programs for the energy saving by means of financing actions for energy diagnoses, substitution of low efficiency air conditioning equipment and refrigerators by ones of high efficiency, as well as heat insulation of house ceilings. The trust Num. 728 FIPATERM, has as its main aim, to design actions tending to the saving and efficient use of the electrical energy in benefit of the clients of Comision Federal de Electricidad (CFE), contracted in domestic tariff. In order to carry out the aims of the Trust Num. 728, the Program of Electrical Energy Saving was implemented -which for advertising purposes was denominated: Programa de Ahorro Sistematico Integral (ASI) [Spanish] El FIPATERM es un organismo de la Administracion Publica Paraestatal, creado para administrar recursos economicos destinados a programas o proyectos que beneficien la economia o el bienestar social del pais. Es un fideicomiso legalmente constituido y que tiene como fin entre otros, desarrollar programas de apoyo al ahorro de energia financiando acciones de diagnosticos energeticos, sustitucion de aparatos de aire acondicionado y refrigeradores de baja eficiencia por alta eficiencia, asi como aislamiento termico de techos de vivienda. El fideicomiso Num. 728 FIPATERM, tiene como fin principal, disenar acciones tendientes al ahorro y uso eficiente de la energia electrica en beneficio de los clientes de la Comision Federal de Electricidad (CFE), contratados en tarifa domestica. Para llevar a cabo los fines del Fideicomiso Num. 728, se implemento el Programa de Ahorro de Energia Electrica, mismo que para fines publicitarios se denomino: Programa de Ahorro Sistematico Integral (ASI)

Predicting DPP-IV inhibitors with machine learning approaches

Science.gov (United States)

Cai, Jie; Li, Chanjuan; Liu, Zhihong; Du, Jiewen; Ye, Jiming; Gu, Qiong; Xu, Jun

2017-04-01

Dipeptidyl peptidase IV (DPP-IV) is a promising Type 2 diabetes mellitus (T2DM) drug target. DPP-IV inhibitors prolong the action of glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP), improve glucose homeostasis without weight gain, edema, and hypoglycemia. However, the marketed DPP-IV inhibitors have adverse effects such as nasopharyngitis, headache, nausea, hypersensitivity, skin reactions and pancreatitis. Therefore, it is still expected for novel DPP-IV inhibitors with minimal adverse effects. The scaffolds of existing DPP-IV inhibitors are structurally diversified. This makes it difficult to build virtual screening models based upon the known DPP-IV inhibitor libraries using conventional QSAR approaches. In this paper, we report a new strategy to predict DPP-IV inhibitors with machine learning approaches involving naïve Bayesian (NB) and recursive partitioning (RP) methods. We built 247 machine learning models based on 1307 known DPP-IV inhibitors with optimized molecular properties and topological fingerprints as descriptors. The overall predictive accuracies of the optimized models were greater than 80%. An external test set, composed of 65 recently reported compounds, was employed to validate the optimized models. The results demonstrated that both NB and RP models have a good predictive ability based on different combinations of descriptors. Twenty "good" and twenty "bad" structural fragments for DPP-IV inhibitors can also be derived from these models for inspiring the new DPP-IV inhibitor scaffold design.

Structural Biology and Molecular Modeling in the Design of Novel DPP-4 Inhibitors

Science.gov (United States)

Scapin, Giovanna

Inhibition of dipeptidyl peptidase IV (DPP-4) is a promising new approach for the treatment of type 2 diabetes. DPP-4 is the enzyme responsible for inactivating the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP), two hormones that play important roles in glucose homeostasis. The potent, orally bioavailable and highly selective small molecule DPP-4 inhibitor sitagliptin has been approved by the FDA as novel drug for the treatment of type 2 diabetes. The comparison between the binding mode of sitagliptin (a β-amino acid) and that of a second class of inhibitors (α-amino acid-based) initially led to the successful identification and design of structurally diverse and highly potent DPP-4 inhibitors. Further analysis of the crystal structure of sitagliptin bound to DPP-4 suggested that the central β-amino butanoyl moiety could be replaced by a rigid group. This was confirmed by molecular modeling, and the resulting cyclohexylamine analogs were synthesized and found to be potent DPP-4 inhibitors. However, the triazolopyrazine was predicted to be distorted in order to fit in the binding pocket, and the crystal structure showed that multiple conformations exist for this moiety. Additional molecular modeling studies were then used to improve potency of the cyclohexylamine series. In addition, a 3-D QSAR method was used to gain insight for reducing off-target DPP-8/9 activities. Novel compounds were thus synthesized and found to be potent DPP-4 inhibitors. Two compounds in particular were designed to be highly selective against off-target "DPP-4 Activity- and/or Structure Homologues" (DASH) enzymes while maintaining potency against DPP-4.

Efficacy of the dual PI3K and mTOR inhibitor NVP-BEZ235 in combination with imatinib mesylate against chronic myelogenous leukemia cell lines

Directory of Open Access Journals (Sweden)

Xin P

2017-04-01

Full Text Available Pengliang Xin, Chuntuan Li, Yan Zheng, Qunyi Peng, Huifang Xiao, Yuanling Huang, Xiongpeng Zhu Department of Haematology, First Hospital of Quanzhou Affiliated to Fujian Medical University, Licheng, Quanzhou, Fujian Province, China Background: Phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR pathway is a therapy target of cancer. We aimed to confirm the effect of dual PI3K/mTOR inhibitor NVP-BEZ235 on proliferation, apoptosis, and autophagy of chronic myelogenous leukemia (CML cells and sensitivity of tyrosine kinase inhibitor in vitro.Methods: Two human CML cell lines, K562 and KBM7R (T315I mutant strain, were used. The proliferation of CML cells was detected by MTS (Owen’s reagent assay. Cell cycle and apoptosis assay were examined by flow cytometric analysis. The phosphorylation levels and the expression levels were both evaluated by Western blot analysis. NVP-BEZ235 in combination with imatinib was also used to reveal the effect on proliferation and apoptosis.Results: NVP-BEZ235 significantly inhibited the proliferation in a time- and dose-dependent manner, and the half-maximal inhibitory concentration values of NVP-BEZ235 inhibiting the proliferation of K562 and KBM7R were 0.37±0.21 and 0.43±0.27 µmol/L, respectively, after 48 h. Cell apoptosis assay showed that NVP-BEZ235 significantly increased the late apoptotic cells. Cell cycle analysis indicated that the cells were mostly arrested in G1/G0 phase after treatment by NVP-BEZ235. In addition, results also found that, after treatment by NVP-BEZ235, phosphorylation levels of Akt kinase and S6K kinase significantly reduced, and the expression levels of cleaved caspase-3 significantly increased; meanwhile, the expression levels of caspase-3, B-cell lymphoma-2, cyclin D1, and cyclin D2 significantly decreased, and the ratio of LC3II/LC3I was significantly increased with increased LC3II expression level. Moreover, imatinib in combination with NVP-BEZ235

Curcumin significantly enhances dual PI3K/Akt and mTOR inhibitor NVP-BEZ235-induced apoptosis in human renal carcinoma Caki cells through down-regulation of p53-dependent Bcl-2 expression and inhibition of Mcl-1 protein stability.

Directory of Open Access Journals (Sweden)

Bo Ram Seo

Full Text Available The PI3K/Akt and mTOR signaling pathways are important for cell survival and growth, and they are highly activated in cancer cells compared with normal cells. Therefore, these signaling pathways are targets for inducing cancer cell death. The dual PI3K/Akt and mTOR inhibitor NVP-BEZ235 completely inhibited both signaling pathways. However, NVP-BEZ235 had no effect on cell death in human renal carcinoma Caki cells. We tested whether combined treatment with natural compounds and NVP-BEZ235 could induce cell death. Among several chemopreventive agents, curcumin, a natural biologically active compound that is extracted from the rhizomes of Curcuma species, markedly induced apoptosis in NVP-BEZ235-treated cells. Co-treatment with curcumin and NVP-BEZ235 led to the down-regulation of Mcl-1 protein expression but not mRNA expression. Ectopic expression of Mcl-1 completely inhibited curcumin plus NVP-NEZ235-induced apoptosis. Furthermore, the down-regulation of Bcl-2 was involved in curcumin plus NVP-BEZ235-induced apoptosis. Curcumin or NVP-BEZ235 alone did not change Bcl-2 mRNA or protein expression, but co-treatment reduced Bcl-2 mRNA and protein expression. Combined treatment with NVP-BEZ235 and curcumin reduced Bcl-2 expression in wild-type p53 HCT116 human colon carcinoma cells but not p53-null HCT116 cells. Moreover, Bcl-2 expression was completely reversed by treatment with pifithrin-α, a p53-specific inhibitor. Ectopic expression of Bcl-2 also inhibited apoptosis in NVP-BE235 plus curcumin-treated cells. In contrast, NVP-BEZ235 combined with curcumin did not have a synergistic effect on normal human skin fibroblasts and normal human mesangial cells. Taken together, combined treatment with NVP-BEZ235 and curcumin induces apoptosis through p53-dependent Bcl-2 mRNA down-regulation at the transcriptional level and Mcl-1 protein down-regulation at the post-transcriptional level.

Minor drug-resistant HIV type-1 variants in breast milk and plasma of HIV type-1-infected Ugandan women after nevirapine single-dose prophylaxis.

Science.gov (United States)

Pilger, Daniel; Hauser, Andrea; Kuecherer, Claudia; Mugenyi, Kizito; Kabasinguzi, Rose; Somogyi, Sybille; Harms, Gundel; Kunz, Andrea

2011-01-01

Nevirapine single-dose (NVP-SD) reduces mother-to-child transmission of HIV type-1 (HIV-1), but frequently induces resistance mutations in the HIV-1 genome. Little is known about drug-resistant HIV-1 variants in the breast milk of women who have taken NVP-SD. Blood and breast milk samples of 39 HIV-1-infected Ugandan women were taken 6-12 weeks after NVP-SD intake. Samples were analysed by population sequencing and allele-specific real-time PCR (AS-PCR) with detection limits for NVP-resistant HIV-1 variants (K103N and Y181C) of D n = 5, G n = 2 and C n = 1). A total of 7 (37%) and 10 (53%) women carried NVP-resistant virus in breast milk and plasma, respectively. Overall, 71% (5/7) women with NVP-resistant HIV-1 in breast milk displayed >1 drug-resistant variant. Resistance in breast milk was higher at week 6 (6/13 samples [46%]) compared with week 12 (1/6 samples [17%]). In total, 10 drug-resistant populations harbouring the K103N and/or Y181C mutation were detected in the 19 breast milk samples; 7 (70%) were caused by resistant minorities (< 5% of the total HIV-1 population). In the four women with drug-resistant virus in both plasma and breast milk, the mutation patterns differed between the two compartments. Minor populations of drug-resistant HIV-1 were frequently found in breast milk of Ugandan women after exposure to NVP-SD. Further studies need to explore the role of minor drug-resistant variants in the postnatal transmission of (resistant) HIV-1.

Identification of Dipeptidyl-Peptidase (DPP)5 and DPP7 in Porphyromonas endodontalis, Distinct from Those in Porphyromonas gingivalis

OpenAIRE

Nishimata, Haruka; Ohara-Nemoto, Yuko; Baba, Tomomi T.; Hoshino, Tomonori; Fujiwara, Taku; Shimoyama, Yu; Kimura, Shigenobu; Nemoto, Takayuki K.

2014-01-01

Dipeptidyl peptidases (DPPs) that liberate dipeptides from the N-terminal end of oligopeptides are crucial for the growth of Porphyromonas species, anaerobic asaccharolytic gram negative rods that utilize amino acids as energy sources. Porphyromonas endodontalis is a causative agent of periapical lesions with acute symptoms and Asp/Glu-specific DPP11 has been solely characterized in this organism. In this study, we identified and characterized two P. endodontalis DPPs, DPP5 and DPP7. Cell-ass...

7 CFR 58.728 - Cooking the batch.

Science.gov (United States)

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Cooking the batch. 58.728 Section 58.728 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Procedures § 58.728 Cooking the batch. Each batch of cheese within the cooker, including the optional...

Hydrophilic porous magnetic poly(GMA-MBAA-NVP) composite microspheres containing oxirane groups: An efficient carrier for immobilizing penicillin G acylase

Energy Technology Data Exchange (ETDEWEB)

Xue, Ping; Su, Weiguang, E-mail: weiguangsu@nxu.edu.cn; Gu, Yaohua; Liu, Haifeng; Wang, Julan

2015-03-15

Magnetic hydrophilic polymeric microspheres containing oxirane groups were prepared by inverse suspension polymerization of glycidyl methacrylate (GMA), N, N′-methylene bisacrylamide (MBAA) and N-vinyl pyrrolidone (NVP) in the existence of formamide, which were denoted as magnetic poly(GMA-MBAA-NVP) microspheres. The magnetic poly(GMA-MBAA-NVP) microspheres were characterized by scanning electron microscopy (SEM), FT-IR spectroscopy, X-ray diffraction (XRD), vibrating sample magnetometer (VSM) and so on. The results showed that poly(GMA-MBAA-NVP) microspheres possessed well spherical shape, narrow size distribution, abundant porous structure, reactive oxirane groups and superparamagnetic properties. Formamide used in the present work served as a modifier, a dispersant and a porogen to form final porous polymer microspheres. The penicillin G acylase (PGA) was covalently immobilized onto the magnetic microspheres through the reaction between the amino groups of enzyme and the oxirane groups on the microspheres for producing 6-aminopenicillanic acid (6-APA). The effects of GMA/NVP ratio and crosslink density on the activity of immobilized PGA were investigated. The highest apparent activity, enzyme loading and coupling yield of immobilized PGA were 821 IU/g, 65.3 mg/g and 42.3% respectively when the mass ratio of GMA/NVP was 1:1 and crosslink density was 60%. Compared with the free PGA, immobilized PGA showed a wider range of pH value and reaction temperature. The relative activity and reaction rate of immobilized PGA remained almost constant after 20 recycles. The magnetic poly(GMA-MBAA-NVP) microspheres would be very promising carriers for immobilizing enzymes in industrial application. - Highlights: • The magnetic poly(GMA-MBAA-NVP) microspheres were successfully synthesized. • Formamide served as a modifier, a dispersant and a porogen to form microspheres. • The magnetic microspheres were highly efficient carriers for immobilizing PGA. • Immobilized PGA

32 CFR 728.93 - Chart of adjuncts.

Science.gov (United States)

2010-07-01

... 32 National Defense 5 2010-07-01 2010-07-01 false Chart of adjuncts. 728.93 Section 728.93 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY PERSONNEL MEDICAL AND DENTAL CARE FOR ELIGIBLE PERSONS AT NAVY MEDICAL DEPARTMENT FACILITIES Adjuncts to Medical Care § 728.93 Chart of...

Hydrophilic porous magnetic poly(GMA-MBAA-NVP) composite microspheres containing oxirane groups: An efficient carrier for immobilizing penicillin G acylase

Science.gov (United States)

Xue, Ping; Su, Weiguang; Gu, Yaohua; Liu, Haifeng; Wang, Julan

2015-03-01

Magnetic hydrophilic polymeric microspheres containing oxirane groups were prepared by inverse suspension polymerization of glycidyl methacrylate (GMA), N, N‧-methylene bisacrylamide (MBAA) and N-vinyl pyrrolidone (NVP) in the existence of formamide, which were denoted as magnetic poly(GMA-MBAA-NVP) microspheres. The magnetic poly(GMA-MBAA-NVP) microspheres were characterized by scanning electron microscopy (SEM), FT-IR spectroscopy, X-ray diffraction (XRD), vibrating sample magnetometer (VSM) and so on. The results showed that poly(GMA-MBAA-NVP) microspheres possessed well spherical shape, narrow size distribution, abundant porous structure, reactive oxirane groups and superparamagnetic properties. Formamide used in the present work served as a modifier, a dispersant and a porogen to form final porous polymer microspheres. The penicillin G acylase (PGA) was covalently immobilized onto the magnetic microspheres through the reaction between the amino groups of enzyme and the oxirane groups on the microspheres for producing 6-aminopenicillanic acid (6-APA). The effects of GMA/NVP ratio and crosslink density on the activity of immobilized PGA were investigated. The highest apparent activity, enzyme loading and coupling yield of immobilized PGA were 821 IU/g, 65.3 mg/g and 42.3% respectively when the mass ratio of GMA/NVP was 1:1 and crosslink density was 60%. Compared with the free PGA, immobilized PGA showed a wider range of pH value and reaction temperature. The relative activity and reaction rate of immobilized PGA remained almost constant after 20 recycles. The magnetic poly(GMA-MBAA-NVP) microspheres would be very promising carriers for immobilizing enzymes in industrial application.

32 CFR 728.13 - Application for care.

Science.gov (United States)

2010-07-01

... Duty § 728.13 Application for care. Possession of an ID card (a green colored DD 2 (with letter suffix... 32 National Defense 5 2010-07-01 2010-07-01 false Application for care. 728.13 Section 728.13 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY PERSONNEL MEDICAL AND DENTAL CARE...

The Vildagliptin Experience - 25 Years Since the Initiation of the Novartis Glucagon-like Peptide-1 Based Therapy Programme and 10 Years Since the First Vildagliptin Registration.

Science.gov (United States)

Foley, James E; Ahrén, Bo

2017-08-01

The discovery of the incretin hormone glucagon like peptide-1 (GLP-1), and its usefulness in the treatment of type 2 diabetes mellitus (T2DM) followed by the finding that dipeptidyl peptidase-4 (DPP-4) inhibition prevents GLP-1 inactivation, led to the discovery of DPP-728. In 1999, studies with DPP-728 established the first proof-of-concept that DPP-4 inhibition improves glycaemic control in patients with T2DM. Further efforts to improve the binding kinetics of DPP-728 resulted in the discovery of vildagliptin (LAF237). In the last 20 years, a plethora of studies conducted by Novartis in collaboration with external investigators has demonstrated the mechanism of action of vildagliptin and its efficacy as monotherapy and as an add-on therapy for patients with T2DM. The studies establish that vildagliptin is a selective DPP-4 inhibitor that blocks GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) inactivation, thereby prolonging their action, resulting in improved glycaemic control. This review aims to discuss the discovery and development of vildagliptin, with an emphasis on mechanism of action and clinical efficacy.

DPP-4 inhibitor des-F-sitagliptin treatment increased insulin exocytosis from db/db mice {beta} cells

Energy Technology Data Exchange (ETDEWEB)

Nagamatsu, Shinya, E-mail: shinya@ks.kyorin-u.ac.jp [Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611 (Japan); Ohara-Imaizumi, Mica; Nakamichi, Yoko; Aoyagi, Kyota; Nishiwaki, Chiyono [Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611 (Japan)

2011-09-09

Highlights: {yields} Anti-diabetic new drug, DPP-4 inhibitor, can affect the insulin exocytosis. {yields} DPP-4 inhibitor treatment altered syntaxin 1 expression. {yields} Treatment of db/db mice with DPP-4 inhibitor increased insulin release. -- Abstract: Incretin promotes insulin secretion acutely. Recently, orally-administered DPP-4 inhibitors represent a new class of anti-hyperglycemic agents. Indeed, inhibitors of dipeptidyl peptidase-IV (DPP-4), sitagliptin, has just begun to be widely used as therapeutics for type 2 diabetes. However, the effects of sitagliptin-treatment on insulin exocytosis from single {beta}-cells are yet unknown. We therefore investigated how sitagliptin-treatment in db/db mice affects insulin exocytosis by treating db/db mice with des-F-sitagliptin for 2 weeks. Perfusion studies showed that 2 weeks-sitagliptin treatment potentiated insulin secretion. We then analyzed insulin granule motion and SNARE protein, syntaxin 1, by TIRF imaging system. TIRF imaging of insulin exocytosis showed the increased number of docked insulin granules and increased fusion events from them during first-phase release. In accord with insulin exocytosis data, des-F-sitagliptin-treatment increased the number of syntaxin 1 clusters on the plasma membrane. Thus, our data demonstrated that 2-weeks des-F-sitagliptin-treatment increased the fusion events of insulin granules, probably via increased number of docked insulin granules and that of syntaxin 1 clusters.

DPP6 domains responsible for its localization and function.

Science.gov (United States)

Lin, Lin; Long, Laura K; Hatch, Michael M; Hoffman, Dax A

2014-11-14

Dipeptidyl peptidase-like protein 6 (DPP6) is an auxiliary subunit of the Kv4 family of voltage-gated K(+) channels known to enhance channel surface expression and potently accelerate their kinetics. DPP6 is a single transmembrane protein, which is structurally remarkable for its large extracellular domain. Included in this domain is a cysteine-rich motif, the function of which is unknown. Here we show that this cysteine-rich domain of DPP6 is required for its export from the ER and expression on the cell surface. Disulfide bridges formed at C349/C356 and C465/C468 of the cysteine-rich domain are necessary for the enhancement of Kv4.2 channel surface expression but not its interaction with Kv4.2 subunits. The short intracellular N-terminal and transmembrane domains of DPP6 associates with and accelerates the recovery from inactivation of Kv4.2, but the entire extracellular domain is necessary to enhance Kv4.2 surface expression and stabilization. Our findings show that the cysteine-rich domain of DPP6 plays an important role in protein folding of DPP6 that is required for transport of DPP6/Kv4.2 complexes out of the ER. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

32 CFR 728.71 - Ex-service maternity care.

Science.gov (United States)

2010-07-01

... 32 National Defense 5 2010-07-01 2010-07-01 false Ex-service maternity care. 728.71 Section 728.71... FOR ELIGIBLE PERSONS AT NAVY MEDICAL DEPARTMENT FACILITIES Other Persons § 728.71 Ex-service maternity... certified by medical authorities that the pregnancy existed prior to entry into service (EPTE), maternity...

The Dual PI3K/mTOR Inhibitor NVP-BEZ235 Is a Potent Inhibitor of ATM- and DNA-PKCs-Mediated DNA Damage Responses

Directory of Open Access Journals (Sweden)

Bipasha Mukherjee

2012-01-01

Full Text Available Inhibitors of PI3K/Akt signaling are being actively developed for tumor therapy owing to the frequent mutational activation of the PI3K-Akt-mTORC1 pathway in many cancers, including glioblastomas (GBMs. NVP-BEZ235 is a novel and potent dual PI3K/mTOR inhibitor that is currently in phase 1/2 clinical trials for advanced solid tumors. Here, we show that NVP-BEZ235 also potently inhibits ATM and DNA-PKcs, the two major kinases responding to ionizing radiation (IR-induced DNA double-strand breaks (DSBs. Consequently, NVP-BEZ235 blocks both nonhomologous end joining and homologous recombination DNA repair pathways resulting in significant attenuation of DSB repair. In addition, phosphorylation of ATMtargets and implementation of the G2/M cell cycle checkpoint are also attenuated by this drug. As a result, NVP-BEZ235 confers an extreme degree of radiosensitization and impairs DSB repair in a panel of GBM cell lines irrespective of their Akt activation status. NVP-BEZ235 also significantly impairs DSB repair in a mouse tumor model thereby validating the efficacy of this drug as a DNA repair inhibitor in vivo. Our results, showing that NVP-BEZ235 is a potent and novel inhibitor of ATM and DNA-PKcs, have important implications for the informed and rational design of clinical trials involving this drug and also reveal the potential utility of NVP-BEZ235 as an effective radiosensitizer for GBMs in the clinic.

The novel orally bioavailable inhibitor of phosphoinositol-3-kinase and mammalian target of rapamycin, NVP-BEZ235, inhibits growth and proliferation in multiple myeloma

International Nuclear Information System (INIS)

Baumann, Philipp; Mandl-Weber, Sonja; Oduncu, Fuat; Schmidmaier, Ralf

2009-01-01

NVP-BEZ235 is a new inhibitor of phosphoinositol-3-kinase (PI3 kinase) and mammalian target of rapamycin (mTOR) whose efficacy in advanced solid tumours is currently being evaluated in a phase I/II clinical trial. Here we show that NVP-BEZ235 inhibits growth in common myeloma cell lines as well as primary myeloma cells at nanomolar concentrations in a time and dose dependent fashion. Further experiments revealed induction of apoptosis in three of four cell lines. Inhibition of cell growth was mainly due to inhibition of myeloma cell proliferation, as shown by the BrdU assay. Cell cycle analysis revealed induction of cell cycle arrest in the G1 phase, which was due to downregulation of cyclin D1, pRb and cdc25a. NVP-BEZ235 inhibited phosphorylation of protein kinase B (Akt), P70S6k and 4E-BP-1. Furthermore we show that the stimulatory effect of CD40-ligand (CD40L), insulin-like growth factor 1 (IGF-1), interleukin-6 (IL-6) and conditioned medium of HS-5 stromal cells on myeloma cell growth is completely abrogated by NVP-BEZ235. In addition, synergism studies revealed synergistic and additive activity of NVP-BEZ235 together with melphalan, doxorubicin and bortezomib. Taken together, inhibition of PI3 kinase/mTOR by NVP-BEZ235 is highly effective and NVP-BEZ235 represents a potential new candidate for targeted therapy in multiple myeloma

DPP4 inhibitors promote biological functions of human endothelial progenitor cells by targeting the SDF-1/CXCR4 signaling pathway

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Liu Feng

2016-01-01

Full Text Available Dipeptidyl peptidase 4 (DPP4 inhibitors(oral hypoglycemic agentshave beneficial effects during the early stages of diabetes. In this study, we evaluated the role of DPP4inhibitorsonthe biological functions of cultured human endothelial progenitor cells (EPCs. After treating EPCs with the DPP4 inhibitors sitagliptin and vildagliptin, we examined the mRNA expression of DPP4, vascular endothelial growth factor (VEGF,VEGF receptor 2 (VEGFR-2,endothelial nitric oxide synthase (eNOS, caspase-3,stromal cell-derived factor-1 (SDF-1, chemokine (C-X-C motif receptor 4 (CXCR4 were measured by RT-PCR. The protein expression of SDF-1 and CXCR4 was determined by Western blot; cell proliferation was tested by the MTT method, and DPP4 activity was determined by a DPP4 assay. Our results revealed that DPP4 expression and activity were inhibited following the treatment with various doses of DPP4 inhibitors. Cell proliferation and the expression of VEGF, VEGFR-2andeNOS were up regulated, while cell apoptosis was inhibited by DPP4 inhibitors in a dose-dependent manner. DPP4 inhibitors activated the SDF-1/CXCR4 signaling pathway, shown by the elevated expression of SDF-1/CXCR4. This further proved that after the SDF-1/CXCR4 signaling pathway was blocked by its inhibitor ADM3100, the effects of DPP4 inhibitors on the proliferation and apoptosis, and the expression of VEGF, VEGFR-2and eNOS of EPCs were significantly reduced. These findings suggest that DPP4 inhibitors promote the biological functions of human EPCs by up regulating the SDF-1/CXCR4 signaling pathway.

Early and late effects of the DPP-4 inhibitor vildagliptin in a rat model of post-myocardial infarction heart failure

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van Gilst Wiek H

2011-09-01

Full Text Available Abstract Background Progressive remodeling after myocardial infarction (MI is a leading cause of morbidity and mortality. Recently, glucagon-like peptide (GLP-1 was shown to have cardioprotective effects, but treatment with GLP-1 is limited by its short half-life. It is rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4, an enzyme which inhibits GLP-1 activity. We hypothesized that the DPP-4 inhibitor vildagliptin will increase levels of GLP-1 and may exert protective effects on cardiac function after MI. Methods Sprague-Dawley rats were either subjected to coronary ligation to induce MI and left ventricular (LV remodeling, or sham operation. Parts of the rats with an MI were pre-treated for 2 days with the DPP-4 inhibitor vildagliptin (MI-Vildagliptin immediate, MI-VI, 15 mg/kg/day. The remainder of the rats was, three weeks after coronary artery ligation, subjected to treatment with DPP-4 inhibitor vildagliptin (MI-Vildagliptin Late, MI-VL or control (MI. At 12 weeks, echocardiography and invasive hemodynamics were measured and molecular analysis and immunohistochemistry were performed. Results Vildagliptin inhibited the DPP-4 enzymatic activity by almost 70% and increased active GLP-1 levels by about 3-fold in plasma in both treated groups (p Conclusion Vildagliptin increases the active GLP-1 level via inhibition of DPP-4, but it has no substantial protective effects on cardiac function in this well established long-term post-MI cardiac remodeling model.

The HSP90 inhibitor NVP-AUY922 radiosensitizes by abrogation of homologous recombination resulting in mitotic entry with unresolved DNA damage.

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Shane Zaidi

Full Text Available Heat shock protein 90 (HSP90 is a molecular chaperone responsible for the conformational maintenance of a number of client proteins that play key roles in cell cycle arrest, DNA damage repair and apoptosis following radiation. HSP90 inhibitors exhibit antitumor activity by modulating the stabilisation and activation of HSP90 client proteins. We sought to evaluate NVP-AUY922, the most potent HSP90 inhibitor yet reported, in preclinical radiosensitization studies.NVP-AUY922 potently radiosensitized cells in vitro at low nanomolar concentrations with a concurrent depletion of radioresistance-linked client proteins. Radiosensitization by NVP-AUY922 was verified for the first time in vivo in a human head and neck squamous cell carcinoma xenograft model in athymic mice, as measured by delayed tumor growth and increased surrogate end-point survival (p = <0.0001. NVP-AUY922 was shown to ubiquitously inhibit resolution of dsDNA damage repair correlating to delayed Rad51 foci formation in all cell lines tested. Additionally, NVP-AUY922 induced a stalled mitotic phenotype, in a cell line-dependent manner, in HeLa and HN5 cell lines irrespective of radiation exposure. Cell cycle analysis indicated that NVP-AUY922 induced aberrant mitotic entry in all cell lines tested in the presence of radiation-induced DNA damage due to ubiquitous CHK1 depletion, but resultant downstream cell cycle effects were cell line dependent.These results identify NVP-AUY922 as the most potent HSP90-mediated radiosensitizer yet reported in vitro, and for the first time validate it in a clinically relevant in vivo model. Mechanistic analysis at clinically achievable concentrations demonstrated that radiosensitization is mediated by the combinatorial inhibition of cell growth and survival pathways, ubiquitous delay in Rad51-mediated homologous recombination and CHK1-mediated G(2/M arrest, but that the contribution of cell cycle perturbation to radiosensitization may be cell line

Diabetes Prevention Program (DPP)

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... Blood Institute (NHLBI) and National Cancer Institute (NCI), began funding a third phase of DPPOS—proposed to ... such as in group settings and over the internet. Ancillary studies of DPP and DPPOS data – Researchers ...

The DPP4 Inhibitor Linagliptin Protects from Experimental Diabetic Retinopathy.

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Dietrich, Nadine; Kolibabka, Matthias; Busch, Stephanie; Bugert, Petra; Kaiser, Ulrike; Lin, Jihong; Fleming, Thomas; Morcos, Michael; Klein, Thomas; Schlotterer, Andrea; Hammes, Hans-Peter

2016-01-01

Dipeptidyl peptidase 4 (DPP4) inhibitors improve glycemic control in type 2 diabetes, however, their influence on the retinal neurovascular unit remains unclear. Vasculo- and neuroprotective effects were assessed in experimental diabetic retinopathy and high glucose-cultivated C. elegans, respectively. In STZ-diabetic Wistar rats (diabetes duration of 24 weeks), DPP4 activity (fluorometric assay), GLP-1 (ELISA), methylglyoxal (LC-MS/MS), acellular capillaries and pericytes (quantitative retinal morphometry), SDF-1a and heme oxygenase-1 (ELISA), HMGB-1, Iba1 and Thy1.1 (immunohistochemistry), nuclei in the ganglion cell layer, GFAP (western blot), and IL-1beta, Icam1, Cxcr4, catalase and beta-actin (quantitative RT-PCR) were determined. In C. elegans, neuronal function was determined using worm tracking software. Linagliptin decreased DPP4 activity by 77% and resulted in an 11.5-fold increase in active GLP-1. Blood glucose and HbA1c were reduced by 13% and 14% and retinal methylglyoxal by 66%. The increase in acellular capillaries was diminished by 70% and linagliptin prevented the loss of pericytes and retinal ganglion cells. The rise in Iba-1 positive microglia was reduced by 73% with linagliptin. In addition, the increase in retinal Il1b expression was decreased by 65%. As a functional correlate, impairment of motility (body bending frequency) was significantly prevented in C. elegans. Our data suggest that linagliptin has a protective effect on the microvasculature of the diabetic retina, most likely due to a combination of neuroprotective and antioxidative effects of linagliptin on the neurovascular unit.

The DPP4 Inhibitor Linagliptin Protects from Experimental Diabetic Retinopathy.

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Nadine Dietrich

Full Text Available Dipeptidyl peptidase 4 (DPP4 inhibitors improve glycemic control in type 2 diabetes, however, their influence on the retinal neurovascular unit remains unclear.Vasculo- and neuroprotective effects were assessed in experimental diabetic retinopathy and high glucose-cultivated C. elegans, respectively. In STZ-diabetic Wistar rats (diabetes duration of 24 weeks, DPP4 activity (fluorometric assay, GLP-1 (ELISA, methylglyoxal (LC-MS/MS, acellular capillaries and pericytes (quantitative retinal morphometry, SDF-1a and heme oxygenase-1 (ELISA, HMGB-1, Iba1 and Thy1.1 (immunohistochemistry, nuclei in the ganglion cell layer, GFAP (western blot, and IL-1beta, Icam1, Cxcr4, catalase and beta-actin (quantitative RT-PCR were determined. In C. elegans, neuronal function was determined using worm tracking software.Linagliptin decreased DPP4 activity by 77% and resulted in an 11.5-fold increase in active GLP-1. Blood glucose and HbA1c were reduced by 13% and 14% and retinal methylglyoxal by 66%. The increase in acellular capillaries was diminished by 70% and linagliptin prevented the loss of pericytes and retinal ganglion cells. The rise in Iba-1 positive microglia was reduced by 73% with linagliptin. In addition, the increase in retinal Il1b expression was decreased by 65%. As a functional correlate, impairment of motility (body bending frequency was significantly prevented in C. elegans.Our data suggest that linagliptin has a protective effect on the microvasculature of the diabetic retina, most likely due to a combination of neuroprotective and antioxidative effects of linagliptin on the neurovascular unit.

Synthesis and structure-activity relationship of N-alkyl Gly-boro-Pro inhibitors of DPP4, FAP, and DPP7.

Science.gov (United States)

Hu, Yi; Ma, Lifu; Wu, Min; Wong, Melissa S; Li, Bei; Corral, Sergio; Yu, Zhizhou; Nomanbhoy, Tyzoon; Alemayehu, Senaiet; Fuller, Stacy R; Rosenblum, Jonathan S; Rozenkrants, Natasha; Minimo, Lauro C; Ripka, William C; Szardenings, Anna K; Kozarich, John W; Shreder, Kevin R

2005-10-01

The structure-activity relationship of various N-alkyl Gly-boro-Pro derivatives against three dipeptidyl peptidases (DPPs) was studied. In a series of N-cycloalkyl analogs, DPP4 and fibroblast activation protein-alpha (FAP) optimally preferred N-cycloheptyl whereas DPP7 tolerated even larger cycloalkyl rings. Gly alpha-carbon derivatization of N-cyclohexyl or N-(2-adamantyl) Gly-boro-Pro resulted in a significant decrease in potency against all the three DPPs.

Thorium and uranium redox-active ligand complexes; reversible intramolecular electron transfer in U(dpp-BIAN)2/ U(dpp-BIAN)2(THE)

Energy Technology Data Exchange (ETDEWEB)

Schelter, Eric John [Los Alamos National Laboratory; Wu, Ruilian [Los Alamos National Laboratory; Scott, Brian L [Los Alamos National Laboratory; Thompson, Joe D [Los Alamos National Laboratory; Batista, Enrique R [Los Alamos National Laboratory; Morris, David E [Los Alamos National Laboratory; Kiplinger, Jaqueline L [Los Alamos National Laboratory

2008-01-01

Actinide complexes of the redox-active ligand dpp-BIAN{sup 2-} (dpp-BIAN = bis(2,6-diisopropylphenyl)acenaphthylene), An(dpp-BIAN){sub 2}(THF){sub n} (An = Th, n = 1; An = U, n = 0, 1) have been prepared. Solid-state magnetic and single-crystal X-ray data for U(dpp-BIAN){sub 2}(THF){sub n} show when n = 0, the complex exists in an f{sup 2}-{pi}*{sup 4} configuration; whereas an intramolecular electron transfer occurs for n = 1, resulting in an f{sup 3}-{pi}*{sup 3} ground configuration. The magnetic data also indicate that interconversion between the two forms of the complex is possible, limited only by the ability of THF vapor to penetrate the solid on cooling of the sample. Spectroscopic data indicate the complex exists solely in the f{sup 2}-{pi}*{sup 4} form in solution, evidenced by the appearance of only small changes in the electronic absorption spectra of the U(dpp-BIAN){sub 2} complex on titration with THF and by measurement of the solution magnetic moment m d{sub 8}-tetrahydrofuran using Evans method. Electrochemistry of the complexes is reported, with small differences observed in wave potentials between metals and in the presence of THF. These data represent the first example of a well-defined, reversible intramolecular electron transfer in an f-element complex and the second example of oxidation state change through dative interaction with a metal ion.

DIPEPTIDYL PEPTIDASE 4 (DPP-4 INHIBITORS FOR THE TREATMENT OF TYPE 2 DIABETES MELLITUS

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Erna Kristin

2016-12-01

Diabetes mellitus (DM merupakan penyakit kronis yang menyebabkan sekitar 1,5 juta kematian pada tahun 2012 menurut Organisasi Kesehatan Dunia (WHO. DM tipe 2 (DMT2 banyaknya 90% dari keseluruhan DM di seluruh dunia. Prevalensi DMT2 meningkat karena obesitas. Pedoman klinis merekomendasikan penggunaan metformin sebagai pengobatan lini pertama kecuali ada kontraindikasi, maka bisa diikuti dengan penambahan 1 atau 2 OADs, seperti sulfonilurea (SU, inhibitor alpha-glucosidase, atau thiazolidinediones (TZD. Baru-baru ini, obat baru golongan dipeptidyl peptidase 4 (DPP-4 inhibitor telah ditambahkan ke algoritma pengobatan. Dipeptidyl peptidase 4 (DPP-4 inhibitor inhibitor adalah kelas obat antidiabetes oral yang menghambat DPP-4 enzim. Sitagliptin, saxagliptin, vildagliptin dan linagliptin yang merupakan golongan dipeptidyl peptidase-4 (DPP-4 inhibitor tersedia untuk pengobatan diabetes tipe 2 di Indonesia dan banyak negara lainnya. DPP-4 inhibitor memiliki khasiat glikemik yang setara. DPP-4 inhibitor menghasilkan peningkatan moderat hemoglobin terglikasi (A1C. Namun uji coba head-to-head jumlahnya terbatas, dan tidak ada data tentang penggunaan penggunaan jangka panjang (lebih dari dua tahun keamanan, kematian, komplikasi diabetes, atau kualitas-hidup pasien. Meskipun DPP-inhibitor tidak digunakan sebagai terapi awal untuk mayoritas pasien dengan diabetes tipe 2, DPP-4 inhibitor dapat digunakan sebagai terapi tambahan di tipe 2 pasien diabetes yang tidak toleran, ada kontraindikasi, atau tidak terkontrol dengan penggunaan metformin, sulfonilurea, atau thiazolidinediones. Peran sebenarnya dari DPP-4 inhibitor di antara beberapa obat lainnya untuk DMT2 tidak begitu jelas. Hanya ada sejumlah kecil studi jangka panjang pada DPP-4 inhibitor menilai penurunan glikemik, kemanjuran, kejadian kardiovaskular, kematian, atau keamanan. Pada pasien dengan gagal ginjal (perkiraan laju filtrasi glomerulus [eGFR] <30 mL / menit kronis dapat menggunakan DPP-4 inhibitor, linagliptin

48 CFR 728.105-1 - Advance payment bonds.

Science.gov (United States)

2010-10-01

... GENERAL CONTRACTING REQUIREMENTS BONDS AND INSURANCE Bonds 728.105-1 Advance payment bonds. (a) Generally, advance payment bonds will not be required in connection with USAID contracts containing an advance... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Advance payment bonds. 728...

32 CFR 728.33 - Nonavailability statement (DD 1251).

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2010-07-01

... 32 National Defense 5 2010-07-01 2010-07-01 false Nonavailability statement (DD 1251). 728.33... Dependents of the Uniformed Services § 728.33 Nonavailability statement (DD 1251). (a) General. Per DODINST.... The following provisions are applicable to nonemergency inpatient care only. A DD 1251 is not required...

40 CFR 52.728 - Control strategy: Nitrogen dioxide. [Reserved

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2010-07-01

... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Control strategy: Nitrogen dioxide. [Reserved] 52.728 Section 52.728 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR...: Nitrogen dioxide. [Reserved] ...

Synthesis, pharmacological evaluation and molecular docking studies of pyrimidinedione based DPP-4 inhibitors as antidiabetic agents

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Jha, Vibhu; Bhadoriya, Kamlendra Singh

2018-04-01

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of newly developed antidiabetic drugs that bock DPP-4. DPP-4 is responsible for degradation of incretins harmones such as GLP-1 (Glucagon like Peptide) and GIP (Gastric inhibitory polypeptide) that maintain blood-glucose level. Pyrimidinedione based compounds were designed and synthesized for DPP-4 inhibitory activity. These heterocycles were designed by taking Alogliptin as a reference DPP-4 inhibitors and synthesized as N-methylated and N-benzylated pyrimidinediones. These compounds were subjected to DPP-4 assay, five out of nine synthesized compounds have shown in vitro DPP-4 inhibitory activity in significant range. Further, molecular docking studies of these compounds were performed on DPP-4 subunit and compared with natural DPP-4 inhibitors like Flavone, Resveratrol, Quercetin, Diprotin A. Docking studies have led to the conclusion that there are some identical amino acid interactions as Tyr 666 and Tyr 662, seen in both synthesized compounds and natural DPP-4 inhibitors. This study completely gives a good scope for further derivatisation and optimization of synthesized compounds to get clinical candidate as DPP-4 inhibitor for antidiabetic activity.

Early and late effects of the DPP-4 inhibitor vildagliptin in a rat model of post-myocardial infarction heart failure

Science.gov (United States)

2011-01-01

Background Progressive remodeling after myocardial infarction (MI) is a leading cause of morbidity and mortality. Recently, glucagon-like peptide (GLP)-1 was shown to have cardioprotective effects, but treatment with GLP-1 is limited by its short half-life. It is rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4), an enzyme which inhibits GLP-1 activity. We hypothesized that the DPP-4 inhibitor vildagliptin will increase levels of GLP-1 and may exert protective effects on cardiac function after MI. Methods Sprague-Dawley rats were either subjected to coronary ligation to induce MI and left ventricular (LV) remodeling, or sham operation. Parts of the rats with an MI were pre-treated for 2 days with the DPP-4 inhibitor vildagliptin (MI-Vildagliptin immediate, MI-VI, 15 mg/kg/day). The remainder of the rats was, three weeks after coronary artery ligation, subjected to treatment with DPP-4 inhibitor vildagliptin (MI-Vildagliptin Late, MI-VL) or control (MI). At 12 weeks, echocardiography and invasive hemodynamics were measured and molecular analysis and immunohistochemistry were performed. Results Vildagliptin inhibited the DPP-4 enzymatic activity by almost 70% and increased active GLP-1 levels by about 3-fold in plasma in both treated groups (p vildagliptin, either early or late, did not reverse cardiac remodeling. ANP (atrial natriuretic peptide) and BNP (brain natriuretic peptide) mRNA levels were significantly increased in all 3 MI groups, but no significant reductions were observed in both vildagliptin groups. Vildagliptin also did not change cardiomyocyte size or capillary density after MI. No effects were detected on glucose level and body weight in the post-MI remodeling model. Conclusion Vildagliptin increases the active GLP-1 level via inhibition of DPP-4, but it has no substantial protective effects on cardiac function in this well established long-term post-MI cardiac remodeling model. PMID:21955567

32 CFR 728.42 - NATO.

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2010-07-01

... § 728.42 NATO. (a) NATO SOFA nations. Belgium, Canada, Denmark, Federal Republic of Germany, France, Greece, Iceland, Italy, Luxembourg, the Netherlands, Norway, Portugal, Spain, Turkey, the United Kingdom...

Association of DPP4 Gene Polymorphisms with Type 2 Diabetes Mellitus in Malaysian Subjects.

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Radwan H Ahmed

Full Text Available Genetic polymorphisms of the Dipeptidyl Peptidase 4 (DPP4 gene may play a role in the etiology of type 2 diabetes mellitus (T2DM. This study aimed to investigate the possible association of single nucleotide polymorphisms (SNPs of the DPP4 gene in Malaysian subjects with T2DM and evaluated whether they had an effect on the serum levels of soluble dipeptidyl peptidase 4 (sDPP-IV.Ten DPP4 SNPs were genotyped by TaqMan genotyping assays in 314 subjects with T2DM and 235 controls. Of these, 71 metabolic syndrome (MetS subjects were excluded from subsequent analysis. The odds ratios (ORs and their 95% confidence interval (CIs were calculated using multiple logistic regression for the association between the SNPs of DPP4 and T2DM. In addition, the serum levels of sDPP-IV were investigated to evaluate the association of the SNPs of DPP4 with the sDPP-IV levels.Dominant, recessive, and additive genetic models were employed to test the association of DPP4 polymorphisms with T2DM, after adjusting for age, race, gender and BMI. The rs12617656 was associated with T2DM in Malaysian subjects in the recessive genetic model (OR = 1.98, p = 0.006, dominant model (OR = 1.95, p = 0.008, and additive model (OR = 1.63, p = 0.001. This association was more pronounced among Malaysian Indians, recessive (OR = 3.21, p = 0.019, dominant OR = 3.72, p = 0.003 and additive model (OR = 2.29, p = 0.0009. The additive genetic model showed that DPP4 rs4664443 and rs7633162 polymorphisms were associated with T2DM (OR = 1.53, p = 0.039, and (OR = 1.42, p = 0.020, respectively. In addition, the rs4664443 G>A polymorphism was associated with increased sDPP-IV levels (p = 0.042 in T2DM subjects.DPP4 polymorphisms were associated with T2DM in Malaysian subjects, and linked to variations in sDPP-IV levels. In addition, these associations were more pronounced among Malaysian Indian subjects.

Renal Effects of DPP-4 Inhibitors: A Focus on Microalbuminuria

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Martin Haluzík

2013-01-01

Full Text Available Incretin-based therapies represent one of the most promising options in type 2 diabetes treatment owing to their good effectiveness with low risk of hypoglycemia and no weight gain. Other numerous potential beneficial effects of incretin-based therapies have been suggested based mostly on experimental and small clinical studies including its beta-cell- and vasculo-protective actions. One of the recently emerged interesting features of dipeptidyl peptidase-4 (DPP-4 inhibitors is its possible protective effect on the diabetic kidney disease. Here, we review the renal effects of DPP-4 inhibitors with special focus on its influence on the onset and progression of microalbuminuria, as presence of microalbuminuria represents an important early sign of kidney damage and is also associated with increased risk of hypoglycemia and cardiovascular complications. Mechanisms underlying possible nephroprotective properties of DPP-4 inhibitors include reduction of oxidative stress and inflammation and improvement of endothelial dysfunction. Effects of DPP-4 inhibitors may be both glucagon-like peptide-1 (GLP-1 dependent and independent. Ongoing prospective studies focused on the nephroprotective effects of DPP-4 inhibitors will further clarify its possible role in the prevention/attenuation of diabetic kidney disease beyond its glucose lowering properties.

Identification of residues on human receptor DPP4 critical for MERS-CoV binding and entry

Energy Technology Data Exchange (ETDEWEB)

Song, Wenfei [Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084 (China); Wang, Ying [Comprehensive AIDS Research Center, Research Center for Public Health, School of Medicine, Tsinghua University, Beijing 100084 (China); Wang, Nianshuang; Wang, Dongli [Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084 (China); Guo, Jianying; Fu, Lili [Comprehensive AIDS Research Center, Research Center for Public Health, School of Medicine, Tsinghua University, Beijing 100084 (China); Shi, Xuanling, E-mail: shixuanlingsk@tsinghua.edu.cn [Comprehensive AIDS Research Center, Research Center for Public Health, School of Medicine, Tsinghua University, Beijing 100084 (China)

2014-12-15

Middle East respiratory syndrome coronavirus (MERS-CoV) infects host cells through binding the receptor binding domain (RBD) on its spike glycoprotein to human receptor dipeptidyl peptidase 4 (hDPP4). Here, we report identification of critical residues on hDPP4 for RBD binding and virus entry through analysis of a panel of hDPP4 mutants. Based on the RBD–hDPP4 crystal structure we reported, the mutated residues were located at the interface between RBD and hDPP4, which potentially changed the polarity, hydrophobic or hydrophilic properties of hDPP4, thereby interfering or disrupting their interaction with RBD. Using surface plasmon resonance (SPR) binding analysis and pseudovirus infection assay, we showed that several residues in hDPP4–RBD binding interface were important on hDPP4–RBD binding and viral entry. These results provide atomic insights into the features of interactions between hDPP4 and MERS-CoV RBD, and also provide potential explanation for cellular and species tropism of MERS-CoV infection. - Highlights: • It has been demonstrated that MERS-CoV infects host cells through binding its envelope spike (S) glycoprotein to the host cellular receptor dipeptidyl peptidase 4 (DPP4). • To identify the critical residues on hDPP4 for RBD binding and virus entry, we constructed a panel of hDPP4 mutants based on structure-guided mutagenesis. • Using surface plasmon resonance (SPR) binding analysis and pseudovirus infection assay, we showed that several residues on hDPP4 had significant impacts on virus/receptor interactions and viral entry. • Our study has provided new insights into the features of interactions between hDPP4 and MERS-CoV RBD, and provides potential explanation for cellular and species tropism of MERS-CoV infection.

Specificity of the second binding protein of the peptide ABC-transporter (Dpp) of Lactococcus lactis IL1403

NARCIS (Netherlands)

Sanz, Y; Toldra, F; Renault, P; Poolman, B

2003-01-01

The genome sequence of Lactococcus lactis IL1403 revealed the presence of a putative peptide-binding protein-dependent ABC-transporter (Dpp). The genes for two peptide-binding proteins (dppA and dppP) precede the membrane components, which include two transmembrane protein genes (dppB and dppC) and

32 CFR 728.51 - General provisions-the “Economy Act.”

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2010-07-01

... 32 National Defense 5 2010-07-01 2010-07-01 false General provisions-the âEconomy Act.â 728.51 Section 728.51 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY PERSONNEL MEDICAL AND DENTAL CARE FOR ELIGIBLE PERSONS AT NAVY MEDICAL DEPARTMENT FACILITIES Beneficiaries of Other Federal Agencies § 728.51 General provisions—th...

Human DPP III – Keap1 Interactions: A Combined Experimental And Computational study

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Mario Gundić

2016-06-01

Full Text Available Kelch-like ECH associated protein 1 (Keap1 is a cellular sensor for oxidative stress and a negative regulator of the transcription factor Nrf2. Keap1 and Nrf2 control expression of nearly 500 genes with diverse cytoprotective functions and the Nrf2-Keap1 signaling pathway is a major regulator of cytoprotective responses to oxidative and electrophilic stress. It was found that the metallopeptidase dipeptidyl peptidase III (DPP III contributes to Nrf2 activation by binding to Keap1, probably by binding to the Kelch domain, and thereby influences Nrf2 activity in cancer. We here first determined that the KD of the DPP III-Kelch domain complex is in the submicromolar range. In order to elucidate the molecular details of the DPP III – Kelch interaction we then built models of the complex between human DPP III and the Keap1 Kelch domain and performed coarse-grained and atomistic simulations of the complexes. In the most stable complexes, the ETGE motif in the DPP III flexible loop binds near the central pore of the six-blade β-propeller Kelch domain. According to the preliminary HD exchange experiments DPP III binds to the more unstructured end of Kelch domain. According to the results of MD simulations DPP III binding to the Kelch domain does not influence the overall DPP III structure or the long-range domain fluctuations. We can conclude that DPP III forms the stable complexes with the Keap1 Kelch domain by inserting the flexible loop into the entrance to the central pore of the six blade β-propeller Kelch domain at its more unstructured, N-terminus. This work is licensed under a Creative Commons Attribution 4.0 International License.

Iro/IRX transcription factors negatively regulate Dpp/TGF-β pathway activity during intestinal tumorigenesis.

Science.gov (United States)

Martorell, Òscar; Barriga, Francisco M; Merlos-Suárez, Anna; Stephan-Otto Attolini, Camille; Casanova, Jordi; Batlle, Eduard; Sancho, Elena; Casali, Andreu

2014-11-01

Activating mutations in Wnt and EGFR/Ras signaling pathways are common in colorectal cancer (CRC). Remarkably, clonal co-activation of these pathways in the adult Drosophila midgut induces "tumor-like" overgrowths. Here, we show that, in these clones and in CRC cell lines, Dpp/TGF-β acts as a tumor suppressor. Moreover, we discover that the Iroquois/IRX-family-protein Mirror downregulates the transcription of core components of the Dpp pathway, reducing its tumor suppressor activity. We also show that this genetic interaction is conserved in human CRC cells, where the Iro/IRX proteins IRX3 and IRX5 diminish the response to TGF-β. IRX3 and IRX5 are upregulated in human adenomas, and their levels correlate inversely with the gene expression signature of response to TGF-β. In addition, Irx5 expression confers a growth advantage in the presence of TGF-β, but is selected against in its absence. Together, our results identify a set of Iro/IRX proteins as conserved negative regulators of Dpp/TGF-β activity. We propose that during the characteristic adenoma-to-carcinoma transition of human CRC, the activity of IRX proteins could reduce the sensitivity to the cytostatic effect of TGF-β, conferring a growth advantage to tumor cells prior to the acquisition of mutations in TGF-β pathway components. © 2014 The Authors.

32 CFR 728.58 - Federal Aviation Agency (FAA) beneficiaries.

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2010-07-01

... 32 National Defense 5 2010-07-01 2010-07-01 false Federal Aviation Agency (FAA) beneficiaries. 728... Federal Agencies § 728.58 Federal Aviation Agency (FAA) beneficiaries. (a) Beneficiaries. Air Traffic Control Specialists (ATCS) of the FAA when appropriate authorization has been furnished by the FAA...

Comparative Study of 17-AAG and NVP-AUY922 in Pancreatic and Colorectal Cancer Cells: Are There Common Determinants of Sensitivity?

Science.gov (United States)

Mayor-López, Leticia; Tristante, Elena; Carballo-Santana, Mar; Carrasco-García, Estefanía; Grasso, Silvina; García-Morales, Pilar; Saceda, Miguel; Luján, Juan; García-Solano, José; Carballo, Fernando; de Torre, Carlos; Martínez-Lacaci, Isabel

2014-10-01

The use of heat shock protein 90 (Hsp90) inhibitors is an attractive antineoplastic therapy. We wanted to compare the effects of the benzoquinone 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin) and the novel isoxazole resorcinol-based Hsp90 inhibitor NVP-AUY922 in a panel of pancreatic and colorectal carcinoma cell lines and in colorectal primary cultures derived from tumors excised to patients. PANC-1, CFPAC-1, and Caco-2 cells were intrinsically resistant to 17-AAG but sensitive to NVP-AUY922. Other cellular models were sensitive to both inhibitors. Human epidermal growth factor receptor receptors and their downstream signaling pathways were downregulated in susceptible cellular models, and concurrently, Hsp70 was induced. Intrinsic resistance to 17-AAG did not correlate with expression of ATP-binding cassette transporters involved in multidrug resistance. Some 17-AAG-resistant, NVP-AUY922-sensitive cell lines lacked quinone oxidoreductase 1 (NQO1) enzyme and activity. However, colorectal LoVo cells still responded to both drugs in spite of having undetectable levels and activity of NQO1. Pharmacological and biologic inhibition of NQO1 did not confer resistance to 17-AAG in sensitive cell lines. Therefore, even though 17-AAG sensitivity is related to NQO1 protein levels and enzymatic activity, the absence of NQO1 does not necessarily convey resistance to 17-AAG in these cellular models. Moreover, NVP-AUY922 does not require NQO1 for its action and is a more potent inhibitor than 17-AAG in these cells. More importantly, we show in this report that NVP-AUY922 potentiates the inhibitory effects of chemotherapeutic agents, such as gemcitabine or oxaliplatin, and other drugs that are currently being evaluated in clinical trials as antitumor agents.

Double incretin receptor knockout (DIRKO) mice reveal an essential role for the enteroinsular axis in transducing the glucoregulatory actions of DPP-IV inhibitors

DEFF Research Database (Denmark)

Hansotia, Tanya; Baggio, Laurie L; Delmeire, Dominique

2004-01-01

with GIPR(-/-) or GLP-1R(-/-) mice. Similarly, glucose-stimulated insulin secretion and the response to forskolin were well preserved in perifused DIRKO islets. Although the dipeptidyl peptidase-IV (DPP-IV) inhibitors valine pyrrolidide (Val-Pyr) and SYR106124 lowered glucose and increased plasma insulin...

Ultrafast Excited-State Dynamics of Diketopyrrolopyrrole (DPP)-Based Materials: Static versus Diffusion-Controlled Electron Transfer Process

KAUST Repository

Alsulami, Qana

2015-06-25

Singlet-to-triplet intersystem crossing (ISC) and photoinduced electron transfer (PET) of platinum(II) containing diketopyrrolopyrrole (DPP) oligomer in the absence and presence of strong electron-acceptor tetracyanoethylene (TCNE) were investigated using femtosecond and nanosecond transient absorption spectroscopy with broadband capabilities. The role of platinum(II) incorporation in those photophysical properties was evaluated by comparing the excited-state dynamics of DPP with and without the metal centers. The steady-state measurements reveal that platinum(II) incorporation facilitates dramatically the interactions between DPP-Pt(acac) and TCNE, resulting in charge transfer (CT) complex formation. The transient absorption spectra in the absence of TCNE reveal ultrafast ISC of DPP-Pt(acac) followed by their long-lived triplet state. In the presence of TCNE, PET from the excited DPP-Pt(acac) and DPP to TCNE, forming the radical ion pairs. The ultrafast PET which occurs statically from DPP-Pt(acac) to TCNE in picosecond regime, is much faster than that from DPP to TCNE (nanosecond time scale) which is diffusion-controlled process, providing clear evidence that PET rate is eventually controlled by the platinum(II) incorporation.

Ultrafast Excited-State Dynamics of Diketopyrrolopyrrole (DPP)-Based Materials: Static versus Diffusion-Controlled Electron Transfer Process

KAUST Repository

Alsulami, Qana; Aly, Shawkat Mohammede; Goswami, Subhadip; Alarousu, Erkki; Usman, Anwar; Schanze, Kirk S.; Mohammed, Omar F.

2015-01-01

Singlet-to-triplet intersystem crossing (ISC) and photoinduced electron transfer (PET) of platinum(II) containing diketopyrrolopyrrole (DPP) oligomer in the absence and presence of strong electron-acceptor tetracyanoethylene (TCNE) were investigated using femtosecond and nanosecond transient absorption spectroscopy with broadband capabilities. The role of platinum(II) incorporation in those photophysical properties was evaluated by comparing the excited-state dynamics of DPP with and without the metal centers. The steady-state measurements reveal that platinum(II) incorporation facilitates dramatically the interactions between DPP-Pt(acac) and TCNE, resulting in charge transfer (CT) complex formation. The transient absorption spectra in the absence of TCNE reveal ultrafast ISC of DPP-Pt(acac) followed by their long-lived triplet state. In the presence of TCNE, PET from the excited DPP-Pt(acac) and DPP to TCNE, forming the radical ion pairs. The ultrafast PET which occurs statically from DPP-Pt(acac) to TCNE in picosecond regime, is much faster than that from DPP to TCNE (nanosecond time scale) which is diffusion-controlled process, providing clear evidence that PET rate is eventually controlled by the platinum(II) incorporation.

The dual PI3K/mTOR inhibitor NVP-BEZ235 induces tumor regression in a genetically engineered mouse model of PIK3CA wild-type colorectal cancer.

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Jatin Roper

Full Text Available To examine the in vitro and in vivo efficacy of the dual PI3K/mTOR inhibitor NVP-BEZ235 in treatment of PIK3CA wild-type colorectal cancer (CRC.PIK3CA mutant and wild-type human CRC cell lines were treated in vitro with NVP-BEZ235, and the resulting effects on proliferation, apoptosis, and signaling were assessed. Colonic tumors from a genetically engineered mouse (GEM model for sporadic wild-type PIK3CA CRC were treated in vivo with NVP-BEZ235. The resulting effects on macroscopic tumor growth/regression, proliferation, apoptosis, angiogenesis, and signaling were examined.In vitro treatment of CRC cell lines with NVP-BEZ235 resulted in transient PI3K blockade, sustained decreases in mTORC1/mTORC2 signaling, and a corresponding decrease in cell viability (median IC(50 = 9.0-14.3 nM. Similar effects were seen in paired isogenic CRC cell lines that differed only in the presence or absence of an activating PIK3CA mutant allele. In vivo treatment of colonic tumor-bearing mice with NVP-BEZ235 resulted in transient PI3K inhibition and sustained blockade of mTORC1/mTORC2 signaling. Longitudinal tumor surveillance by optical colonoscopy demonstrated a 97% increase in tumor size in control mice (p = 0.01 vs. a 43% decrease (p = 0.008 in treated mice. Ex vivo analysis of the NVP-BEZ235-treated tumors demonstrated a 56% decrease in proliferation (p = 0.003, no effects on apoptosis, and a 75% reduction in angiogenesis (p = 0.013.These studies provide the preclinical rationale for studies examining the efficacy of the dual PI3K/mTOR inhibitor NVP-BEZ235 in treatment of PIK3CA wild-type CRC.

20 CFR 404.728 - Evidence a marriage has ended.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Evidence a marriage has ended. 404.728... DISABILITY INSURANCE (1950- ) Evidence Evidence of Age, Marriage, and Death § 404.728 Evidence a marriage has ended. (a) When evidence is needed that a marriage has ended. If you apply for benefits as the insured...

Association of DPP4 Gene Polymorphisms with Type 2 Diabetes Mellitus in Malaysian Subjects

OpenAIRE

Ahmed, Radwan H.; Huri, Hasniza Zaman; Al-Hamodi, Zaid; Salem, Sameer D.; Al-absi, Boshra; Muniandy, Sekaran

2016-01-01

Background Genetic polymorphisms of the Dipeptidyl Peptidase 4 (DPP4) gene may play a role in the etiology of type 2 diabetes mellitus (T2DM). This study aimed to investigate the possible association of single nucleotide polymorphisms (SNPs) of the DPP4 gene in Malaysian subjects with T2DM and evaluated whether they had an effect on the serum levels of soluble dipeptidyl peptidase 4 (sDPP-IV). Method Ten DPP4 SNPs were genotyped by TaqMan genotyping assays in 314 subjects with T2DM and 235 co...

The DPP-4 inhibitor vildagliptin impacts the gut microbiota and prevents disruption of intestinal homeostasis induced by a Western diet in mice.

Science.gov (United States)

Olivares, Marta; Neyrinck, Audrey M; Pötgens, Sarah A; Beaumont, Martin; Salazar, Nuria; Cani, Patrice D; Bindels, Laure B; Delzenne, Nathalie M

2018-05-25

Dipeptidyl peptidase 4 (DPP-4) inhibitors are agents designed to increase the half-life of incretins. Although they are administered orally, little is known about their effects on the gut microbiota and functions, despite the fact that some bacteria present in the gut microbiota exhibit DPP-4-like activity. Our objective was to study the impact of the DPP-4 inhibitor vildagliptin on gut functions and the intestinal ecosystem in a murine model of obesity induced by a Western diet (WD). Twenty seven male C57BL/6J mice were randomised to receive a control diet, a WD (45% kJ from fat and 17% kJ from sucrose) or a WD + vildagliptin (0.6 mg/ml in drinking water) for 8 weeks. Vildagliptin significantly reduced DPP-4 activity in the caecal content and faeces. Vildagliptin impacted on the composition of the gut microbiota and its metabolic activity. It mainly decreased Oscillibacter spp. (a direct effect independent of DPP-4 activity was shown on cultured O. valericigenes), increased Lactobacillus spp. and propionate, and reduced the ligands of Toll-like receptors 2 and 4. Vildagliptin protected against the reductions in crypt depth and ileal expression of antimicrobial peptides induced by the WD. In the liver, the expression of immune cell populations (Cd3g and Cd11c [also known as Itgax]) and cytokines was decreased in the WD + vildagliptin-fed mice compared with the WD-fed group. Ex vivo exposure of precision-cut liver slices to vildagliptin showed that this response was not related to a direct effect of the drug on the liver tissue. Our study is the first to consider the DPP-4-like activity of the gut microbiota as a target of DPP-4 inhibition. We propose that vildagliptin exerts beneficial effects at the intestinal level in association with modulation of gut microbiota, with consequences for hepatic immunity. If relevant in humans, this could open new therapeutic uses of DPP-4 inhibition to tackle gut dysfunctions in different pathophysiological contexts. The

30 CFR 250.266 - After receiving the DPP or DOCD, what will MMS do?

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false After receiving the DPP or DOCD, what will MMS do? 250.266 Section 250.266 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR... Decision Process for the Dpp Or Docd § 250.266 After receiving the DPP or DOCD, what will MMS do? (a...

Reduced Graphene Oxide Decorated Na3V2(PO43 Microspheres as Cathode Material With Advanced Sodium Storage Performance

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Hezhang Chen

2018-05-01

Full Text Available Reduced graphene oxide (rGO sheet decorated Na3V2(PO43 (NVP microspheres were successfully synthesized by spray-drying method. The NVP microspheres were embedded by rGO sheets, and the surface of the particles were coated by rGO sheets and amorphous carbon. Thus, the carbon conductive network consisted of rGO sheets and amorphous carbon generated in the cathode material. NVP microspheres decorated with different content of rGO (about 0, 4, 8, and 12 wt% were investigated in this study. The electrochemical performance of NVP exhibited a significant enhancement after rGO introduction. The electrode containing about 8 wt% rGO (NVP/G8 showed the best rate and cycle performance. NVP/G8 electrode exhibited the discharge capacity of 64.0 mAh g−1 at 70°C, and achieved high capacity retention of 95.5% after cycling at 10°C for 100 cycles. The polarization of the electrode was inhibited by the introduction of rGO sheets. Meanwhile, compared with the pristine NVP electrode, NVP/G8 electrode exhibited small resistance and high diffusion coefficient of sodium ions.

Physiological and pharmacological mechanisms through which the DPP-4 inhibitor sitagliptin regulates glycemia in mice

DEFF Research Database (Denmark)

Waget, Aurélie; Cabou, Cendrine; Masseboeuf, Myriam

2011-01-01

Inhibition of dipeptidyl peptidase-4 (DPP-4) activity improves glucose homeostasis through a mode of action related to the stabilization of the active forms of DPP-4-sensitive hormones such as the incretins that enhance glucose-induced insulin secretion. However, the DPP-4 enzyme is highly expres...

Teneligliptin Decreases Uric Acid Levels by Reducing Xanthine Dehydrogenase Expression in White Adipose Tissue of Male Wistar Rats

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Chihiro Moriya

2016-01-01

Full Text Available We investigated the effects of teneligliptin on uric acid metabolism in male Wistar rats and 3T3-L1 adipocytes. The rats were fed with a normal chow diet (NCD or a 60% high-fat diet (HFD with or without teneligliptin for 4 weeks. The plasma uric acid level was not significantly different between the control and teneligliptin groups under the NCD condition. However, the plasma uric acid level was significantly decreased in the HFD-fed teneligliptin treated rats compared to the HFD-fed control rats. The expression levels of xanthine dehydrogenase (Xdh mRNA in liver and epididymal adipose tissue of NCD-fed rats were not altered by teneligliptin treatment. On the other hand, Xdh expression was reduced significantly in the epididymal adipose tissue of the HFD-fed teneligliptin treated rats compared with that of HFD-fed control rats, whereas Xdh expression in liver did not change significantly in either group. Furthermore, teneligliptin significantly decreased Xdh expression in 3T3-L1 adipocytes. DPP-4 treatment significantly increased Xdh expression in 3T3-L1 adipocytes. With DPP-4 pretreatment, teneligliptin significantly decreased Xdh mRNA expression compared to the DPP-4-treated 3T3-L1 adipocytes. In conclusion, our studies suggest that teneligliptin reduces uric acid levels by suppressing Xdh expression in epididymal adipose tissue of obese subjects.

Boro-norleucine as a P1 residue for the design of selective and potent DPP7 inhibitors.

Science.gov (United States)

Shreder, Kevin R; Wong, Melissa S; Corral, Sergio; Yu, Zhizhou; Winn, David T; Wu, Min; Hu, Yi; Nomanbhoy, Tyzoon; Alemayehu, Senaiet; Fuller, Stacy R; Rosenblum, Jonathan S; Kozarich, John W

2005-10-01

Dipeptide-based inhibitors with C-substituted (alkyl or aminoalkyl) alpha-amino acids in the P2 position and boro-norleucine (boro-Nle) in the P1 position were synthesized. Relative to boro-proline, boro-Nle as a P1 residue was shown able to significantly dial out DPP4, FAP, DPP8, and DPP9 activity. Dab-boro-Nle (4g) proved to be the most selective and potent DPP7 inhibitor with a DPP7 IC50 value of 480 pM.

Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes

DEFF Research Database (Denmark)

Herman, Gary A; Bergman, Arthur; Stevens, Catherine

2006-01-01

CONTEXT: In response to a meal, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are released and modulate glycemic control. Normally these incretins are rapidly degraded by dipeptidyl peptidase-4 (DPP-4). DPP-4 inhibitors are a novel class of oral antihyperglyce......CONTEXT: In response to a meal, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are released and modulate glycemic control. Normally these incretins are rapidly degraded by dipeptidyl peptidase-4 (DPP-4). DPP-4 inhibitors are a novel class of oral...... antihyperglycemic agents in development for the treatment of type 2 diabetes. The degree of DPP-4 inhibition and the level of active incretin augmentation required for glucose lowering efficacy after an oral glucose tolerance test (OGTT) were evaluated. OBJECTIVE: The objective of the study was to examine...... concentrations; and sitagliptin pharmacokinetics. RESULTS: Sitagliptin dose-dependently inhibited plasma DPP-4 activity over 24 h, enhanced active GLP-1 and GIP levels, increased insulin/C-peptide, decreased glucagon, and reduced glycemic excursion after OGTTs administered at 2 and 24 h after single oral 25...

32 CFR 728.102 - Care from other than Federal sources.

Science.gov (United States)

2010-07-01

... MEDICAL AND DENTAL CARE FOR ELIGIBLE PERSONS AT NAVY MEDICAL DEPARTMENT FACILITIES Reservists-Continued Treatment, Return to Limited Duty, Separation, or Retirement for Physical Disability § 728.102 Care from... 32 National Defense 5 2010-07-01 2010-07-01 false Care from other than Federal sources. 728.102...

Characterization of five ECF sigma factors in the genome of Pseudomonas syringae pv. syringae B728a.

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Poulami Basu Thakur

Full Text Available Pseudomonas syringae pv. syringae B728a, a bacterial pathogen of bean, utilizes large surface populations and extracellular signaling to initiate a fundamental change from an epiphytic to a pathogenic lifestyle. Extracytoplasmic function (ECF sigma (σ factors serve as important regulatory factors in responding to various environmental signals. Bioinformatic analysis of the B728a genome revealed 10 ECF sigma factors. This study analyzed deletion mutants of five previously uncharacterized ECF sigma factor genes in B728a, including three FecI-type ECF sigma factors (ECF5, ECF6, and ECF7 and two ECF sigma factors placed in groups ECF11 and ECF18. Transcriptional profiling by qRT-PCR analysis of ECF sigma factor mutants was used to measure expression of their associated anti-sigma and outer membrane receptor proteins, and expression of genes associated with production of extracellular polysaccharides, fimbriae, glycine betaine and syringomycin. Notably, the B728aΔecf7 mutant displayed reduced swarming and had decreased expression of CupC fimbrial genes. Growth and pathogenicity assays, using a susceptible bean host, revealed that none of the tested sigma factor genes are required for in planta growth and lesion formation.

The Effect of DPP-4 Inhibitors on Metabolic Parameters in Patients with Type 2 Diabetes

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Eun Yeong Choe

2014-06-01

Full Text Available BackgroundWe evaluated the effects of two dipeptidyl peptidase-4 (DPP-4 inhibitors, sitagliptin and vildagliptin, on metabolic parameters in patients with type 2 diabetes mellitus.MethodsA total of 170 type 2 diabetes patients treated with sitagliptin or vildagliptin for more than 24 weeks were selected. The patients were separated into two groups, sitagliptin (100 mg once daily, n=93 and vildagliptin (50 mg twice daily, n=77. We compared the effect of each DPP-4 inhibitor on metabolic parameters, including the fasting plasma glucose (FPG, postprandial glucose (PPG, glycated hemoglobin (HbA1c, and glycated albumin (GA levels, and lipid parameters at baseline and after 24 weeks of treatment.ResultsThe HbA1c, FPG, and GA levels were similar between the two groups at baseline, but the sitagliptin group displayed a higher PPG level (P=0.03. After 24 weeks of treatment, all of the glucose-related parameters were significantly decreased in both groups (P=0.001. The levels of total cholesterol and triglycerides were only reduced in the vildagliptin group (P=0.001, although the sitagliptin group received a larger quantity of statins than the vildagliptin group (P=0.002.The mean change in the glucose- and lipid-related parameters after 24 weeks of treatment were not significantly different between the two groups (P=not significant. Neither sitagliptin nor vildagliptin treatment was associated with a reduction in the high sensitive C-reactive protein level (P=0.714.ConclusionVildagliptin and sitagliptin exert a similar effect on metabolic parameters, but vildagliptin exerts a more potent beneficial effect on lipid parameters.

Changes in Adenosine Deaminase Activity in Patients with Type 2 Diabetes Mellitus and Effect of DPP-4 Inhibitor Treatment on ADA Activity

Science.gov (United States)

Lee, Jae-Geun; Kang, Dong Gu; Yu, Jung Re; Kim, Youngree; Kim, Jinsoek; Koh, Gwanpyo

2011-01-01

Background Dipeptidyl peptidase 4 (DPP-4, also known as CD26) binds with adenosine deaminase (ADA) to activate T lymphocytes. Here, we investigated whether ADA activity is specifically affected by treatment with DPP-4 inhibitor (DPP4I) compared with other anti-diabetic agents. Methods Fasting ADA activity, in addition to various metabolic and biochemical parameters, were measured in 262 type 2 diabetes mellitus (T2DM) patients taking various anti-diabetic agents and in 46 non-diabetic control subjects. Results ADA activity was increased in T2DM patients compared with that in non-diabetic control subjects (mean±standard error, 23.1±0.6 U/L vs. 18.6±0.8 U/L; PADA activity was correlated with fasting plasma glucose (r=0.258, P9%) showed significantly increased ADA activity (21.1±0.8 U/L vs. 25.4±1.6 U/L; PADA activity in T2DM patients did not differ from those of other oral anti-diabetic agents or insulin. T2DM patients on metformin monotherapy showed a lower ADA activity (20.9±1.0 U/L vs. 28.1±2.8 U/L; PADA activity is increased in T2DM patients compared to that in non-diabetic patients, is positively correlated with blood glucose level, and that DPP4I has no additional specific effect on ADA activity, except for a glycemic control- or HbA1c-dependent effect. PMID:21738897

Changes in Adenosine Deaminase Activity in Patients with Type 2 Diabetes Mellitus and Effect of DPP-4 Inhibitor Treatment on ADA Activity.

Science.gov (United States)

Lee, Jae-Geun; Kang, Dong Gu; Yu, Jung Re; Kim, Youngree; Kim, Jinsoek; Koh, Gwanpyo; Lee, Daeho

2011-04-01

Dipeptidyl peptidase 4 (DPP-4, also known as CD26) binds with adenosine deaminase (ADA) to activate T lymphocytes. Here, we investigated whether ADA activity is specifically affected by treatment with DPP-4 inhibitor (DPP4I) compared with other anti-diabetic agents. Fasting ADA activity, in addition to various metabolic and biochemical parameters, were measured in 262 type 2 diabetes mellitus (T2DM) patients taking various anti-diabetic agents and in 46 non-diabetic control subjects. ADA activity was increased in T2DM patients compared with that in non-diabetic control subjects (mean±standard error, 23.1±0.6 U/L vs. 18.6±0.8 U/L; PADA activity was correlated with fasting plasma glucose (r=0.258, P9%) showed significantly increased ADA activity (21.1±0.8 U/L vs. 25.4±1.6 U/L; PADA activity in T2DM patients did not differ from those of other oral anti-diabetic agents or insulin. T2DM patients on metformin monotherapy showed a lower ADA activity (20.9±1.0 U/L vs. 28.1±2.8 U/L; PADA activity is increased in T2DM patients compared to that in non-diabetic patients, is positively correlated with blood glucose level, and that DPP4I has no additional specific effect on ADA activity, except for a glycemic control- or HbA1c-dependent effect.

Alogliptin: a new addition to the class of DPP-4 inhibitors

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Radha Andukuri

2009-07-01

Full Text Available Radha Andukuri, Andjela Drincic, Marc RendellDivision of Endocrinology, Department of Medicine, Creighton University School of Medicine, Omaha, Nebraska, USABackground: Alogliptin is an oral antihyperglycemic agent that is a selective inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4. Inhibition of DPP-4 elevates levels of the incretin hormones glucagon-like peptide (GLP-1 and glucose-dependent insulinotropic polypeptide (GIP by preventing their degradation.Objective: To review the evolution of alogliptin and its pharmacokinetics, pharmacodynamics, clinical efficacy and adverse effects. In addition, we compared alogliptin to other DPP-4 inhibitors.Methods: A comprehensive literature search was performed using the term ‘alogliptin’. Original research articles and review articles as well as scientific abstracts were included. Results: Alogliptin raises postprandial levels of GLP-1. It has excellent bioavailability exhibiting a median Tmax ranging from 1 to 2 hours and a mean half-life of 12.4 to 21.4 hours across all doses. When given as monotherapy, mean hemoglobin A1c (HbA1c reductions achieved were 0.5% to 0.6%. Combination therapy yielded similar reductions (−0.5% with metformin, −0.6% with glyburide, −0.8% with pioglitazone and –0.6% with insulin. Administration of alogliptin does not promote weight loss but has not resulted in weight gain. The agent is relatively well tolerated with few adverse effects, the major finding being a marginally higher rate of skin events, primarily pruritus.Conclusions: Alogliptin causes significant reductions in HbA1c when used alone or in combination with other oral agents in patients with type 2 diabetes similar to other DPP-4 inhibitors in current clinical use. The side effect profile also does not differ from that of other DPP-4 inhibitors. However, long-term studies are necessary before the place of alogliptin in the management of type 2 diabetes can be established.Keywords: alogliptin, DPP

Comparison between SGLT2 inhibitors and DPP4 inhibitors added to insulin therapy in type 2 diabetes: a systematic review with indirect comparison meta-analysis.

Science.gov (United States)

Min, Se Hee; Yoon, Jeong-Hwa; Hahn, Seokyung; Cho, Young Min

2017-01-01

Both sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors can be used to treat patients with type 2 diabetes mellitus (T2DM) that is inadequately controlled with insulin therapy, and yet there has been no direct comparison of these two inhibitors. We searched MEDLINE, EMBASE, LILACS, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov through June 2015. Randomized controlled trials published in English that compare SGLT2 inhibitor plus insulin (SGLT2i/INS) with placebo plus insulin or DPP4 inhibitor plus insulin (DPP4i/INS) with placebo plus insulin in patients with T2DM were selected. Data on the study characteristics, efficacy and safety outcomes were extracted. We compared the efficacy and safety between SGLT2i/INS and DPP4i/INS indirectly with covariates adjustment. Risk of potential bias was assessed. Fourteen eligible randomized controlled trials comprising 6980 patients were included (five SGLT2 inhibitor studies and nine DPP4 inhibitor studies). Covariate-adjusted indirect comparison using meta-regression analyses revealed that SGLT2i/INS achieved greater reduction in HbA 1c [weighted mean difference (WMD) -0.24%, 95% confidence interval (CI) -0.43 to -0.05%], fasting plasma glucose (WMD -18.0 mg/dL, 95% CI -28.5 to -7.6 mg/dL) and body weight (WMD -2.38 kg, 95% CI -3.18 to -1.58 kg) from baseline than DPP4i/INS without increasing the risk of hypoglycaemia (relative risks 1.19, 95% CI 0.78 to 1.82). Sodium glucose cotransporter 2 inhibitors achieved better glycaemic control and greater weight reduction than DPP4 inhibitors without increasing the risk of hypoglycaemia in patients with T2DM that is inadequately controlled with insulin. There has been no direct comparison of SGLT2 inhibitors and DPP4 inhibitors in patients with T2DM inadequately controlled with insulin therapy. In this study, we performed indirect meta-analysis comparing SGLT2 inhibitors and DPP4 inhibitors added to insulin

Triplet State Formation in Photovoltaic Blends of DPP-Type Copolymers and PC71BM

KAUST Repository

Ochsmann, Julian R.; Chandran, Deepak; Gehrig, Dominik W.; Anwar, Husna; Madathil, Pramod Kandoth; Lee, Kwang-Sup; Laquai, Fré dé ric

2015-01-01

The exciton dynamics in pristine films of two structurally related low-bandgap diketopyrrolopyrrole (DPP)-based donor–acceptor copolymers and the photophysical processes in bulk heterojunction solar cells using DPP copolymer:PC71BM blends

The persistent inhibitory properties of saxagliptin on renal dipeptidyl peptidase-4: Studies with HK-2 cells in vitro and normal rats in vivo

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Masako Uchii

2017-11-01

Full Text Available Saxagliptin, a potent and selective DPP-4 inhibitor, exhibits a slow dissociation from DPP-4. We investigated the sustained effects of saxagliptin on renal DPP-4 activity in a washout study using renal tubular (HK-2 cells, and in a pharmacodynamic study using normal rats. In HK-2 cells, the inhibitory potency of saxagliptin on DPP-4 activity persisted after washout, while that of sitagliptin was clearly reduced. In normal rats, a single treatment of saxagliptin or sitagliptin inhibited the plasma DPP-4 activity to similar levels. The inhibitory action of saxagliptin on the renal DPP-4 activity was retained, even when its inhibitory effect on the plasma DPP-4 activity disappeared. However, the inhibitory action of sitagliptin on the renal DPP-4 activity was abolished in correlation with the inhibition of the plasma DPP-4 activity. In situ staining showed that saxagliptin suppressed the DPP-4 activity in both glomerular and tubular cells and its inhibitory effects were significantly higher than those of sitagliptin. Saxagliptin exerted a sustained inhibitory effect on the renal DPP-4 activity in vitro and in vivo. The long binding action of saxagliptin in renal tubular cells might involve the sustained inhibition of renal DPP-4.

Commercial broth microdilution panel validation and reproducibility trials for NVP PDF-713 (LBM 415), a novel inhibitor of bacterial peptide deformylase.

Science.gov (United States)

Fritsche, T R; Moet, G J; Jones, R N

2004-09-01

NVP PDF-713 (LBM 415) is a peptide deformylase inhibitor being progressed into clinical trials. Dry-form broth microdilution panels of NVP PDF-713 were compared to reference MIC panels of 552 recent clinical isolates. Most (99.2%) dry-form MIC results were within +/- 1 log(2) dilution of the reference panel MICs. Of the bacteria tested, Streptococcus pneumoniae and Haemophilus influenzae showed a bias towards higher and lower MICs, respectively. Same-day and between-day reproducibility tests showed that 98.9% and 96.7% of MIC values, respectively, were within +/- 1 log(2) dilution step, thereby demonstrating a high degree of reliability of the dry-form MIC product for clinical studies.

The effect of malnutrition on the pharmacokinetics and virologic outcomes of lopinavir, efavirenz and nevirapine in food insecure HIV-infected children in Tororo, Uganda.

Science.gov (United States)

Bartelink, Imke H; Savic, Rada M; Dorsey, Grant; Ruel, Theodore; Gingrich, David; Scherpbier, Henriette J; Capparelli, Edmund; Jullien, Vincent; Young, Sera L; Achan, Jane; Plenty, Albert; Charlebois, Edwin; Kamya, Moses; Havlir, Diane; Aweeka, Francesca

2015-03-01

Malnutrition may impact the pharmacokinetics (PKs) of antiretroviral medications and virologic responses in HIV-infected children. The authors therefore evaluated the PK of nevirapine (NVP), efavirenz (EFV) and lopinavir (LPV) in associations with nutritional status in a cohort of HIV-infected Ugandan children. Sparse dried blood spot samples from Ugandan children were used to estimate plasma concentrations. Historical PK data from children from 3 resource-rich countries (RRC) were utilized to develop the PK models. Concentrations in 330 dried blood spot from 163 Ugandan children aged 0.7-7 years were analyzed in reference to plasma PK data (1189 samples) from 204 children from RRC aged 0.5-12 years. Among Ugandan children, 48% was malnourished (underweight, thin or stunted). Compared to RRC, Ugandan children exhibited reduced bioavailability of EFV and LPV; 11% (P=0.045) and 18% (P=0.008), respectively. In contrast, NVP bioavailability was 46% higher in Ugandan children (PChildren receiving LPV, EFV or NVP had comparable risk of virologic failure. Among children on NVP, low height and weight for age Z scores were associated with reduced risk of virologic failure (P=0.034, P=0.068, respectively). Ugandan children demonstrated lower EFV and LPV and higher NVP exposure compared to children in RRC, perhaps reflecting the consequence of malnutrition on bioavailability. In children receiving NVP, the relation between exposure, malnutrition and outcome turned out to be marginally significant. Further investigations are warranted using more intensive PK measurements and adequate adherence assessments, to further assess causes of virologic failure in Ugandan children.

DPP4 deficiency exerts protective effect against H2O2 induced oxidative stress in isolated cardiomyocytes.

Directory of Open Access Journals (Sweden)

Hui-Chun Ku

Full Text Available Apart from the antihyperglycemic effects, DPP4 inhibitors and GLP-1 molecules are involved in the preservation of cardiac functions. We have demonstrated that DPP4-deficient rats possess resistance to endotoxemia and ischemia/reperfusion stress. However, whether the decrease of DPP4 activity simply augmented the GLP-1 signaling or that such decrease resulted in a change of cellular function remain unclear. Accordingly, we investigated the responses of H(2O(2-induced oxidative stress in adult wild-type and DPP4-deficient rats isolated cardiomyocytes. The coadministration of GLP-1 or DPP4 inhibitor was also performed to define the mechanisms. Cell viability, ROS concentration, catalase activity, glucose uptake, prosurvival, proapoptotic signaling, and contractile function were examined after cells exposed to H(2O(2. DPP4-deficient cardiomyocytes were found to be resistant to H(2O(2-induced cell death via activating AKT signaling, enhancing glucose uptake, preserving catalase activity, diminishing ROS level and proapoptotic signaling. GLP-1 concentration-dependently improved cell viability in wild-type cardiomyocyte against ROS stress, and the ceiling response concentration (200 nM was chosen for studies. GLP-1 was shown to decrease H(2O(2-induced cell death by its receptor-dependent AKT pathway in wild-type cardiomyocytes, but failed to cause further activation of AKT in DPP4-deficient cardiomyocytes. Acute treatment of DPP4 inhibitor only augmented the protective effect of low dose GLP-1, but failed to alter fuel utilization or ameliorate cell viability in wild-type cardiomyocytes after H(2O(2 exposure. The improvement of cell viability after H(2O(2 exposure was correlated with the alleviation of cellular contractile dysfunction in both DPP4-deficient and GLP-1 treated wild-type cardiomyocytes. These findings demonstrated that GLP-1 receptor-dependent pathway is important and exert protective effect in wild-type cardiomyocyte. Long term loss of

Identification of novel dipeptidyl peptidase IV (DPP-IV) inhibitory peptides in camel milk protein hydrolysates.

Science.gov (United States)

Nongonierma, Alice B; Paolella, Sara; Mudgil, Priti; Maqsood, Sajid; FitzGerald, Richard J

2018-04-01

Nine novel dipeptidyl peptidase IV (DPP-IV) inhibitory peptides (FLQY, FQLGASPY, ILDKEGIDY, ILELA, LLQLEAIR, LPVP, LQALHQGQIV, MPVQA and SPVVPF) were identified in camel milk proteins hydrolysed with trypsin. This was achieved using a sequential approach combining liquid chromatography tandem mass spectrometry (LC-MS/MS), qualitative/quantitative structure activity relationship (QSAR) and confirmatory studies with synthetic peptides. The most potent camel milk protein-derived DPP-IV inhibitory peptides, LPVP and MPVQA, had DPP-IV half maximal inhibitory concentrations (IC 50 ) of 87.0 ± 3.2 and 93.3 ± 8.0 µM, respectively. DPP-IV inhibitory peptide sequences identified within camel and bovine milk protein hydrolysates generated under the same hydrolysis conditions differ. This was linked to differences in enzyme selectivity for peptide bond cleavage of camel and bovine milk proteins as well as dissimilarities in their amino acid sequences. Camel milk proteins contain novel DPP-IV inhibitory peptides which may play a role in the regulation of glycaemia in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

32 CFR 728.14 - Pay patients.

Science.gov (United States)

2010-07-01

... Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY PERSONNEL MEDICAL AND DENTAL CARE FOR ELIGIBLE PERSONS AT NAVY MEDICAL DEPARTMENT FACILITIES Members of the Uniformed Services on Active Duty § 728.14 Pay patients. Care is provided on a reimbursable basis to: Coast Guard active duty officers...

Attenuation of renovascular damage in Zucker diabetic fatty rat by NWT-03, an egg protein hydrolysate with ACE- and DPP4-inhibitory Activity.

Directory of Open Access Journals (Sweden)

Yumei Wang

Full Text Available BACKGROUND: Dipeptidyl peptidase 4 (DPP4 and angiotensin-converting enzyme (ACE are important target enzymes in glycemic control and renovascular protection. Here, we studied the effect of NWT-03, an egg protein hydrolysate with DPP4- and ACE-inhibitory activity, on renovascular damage in Zucker diabetic fatty (ZDF rats. Comparisons were made to rats treated with vildagliptin (VIL, included as a positive control for the effect of DPP4 inhibition. METHODS: ZDF rats received NWT-03 (1 g/kg/day or VIL (3 mg/kg/day from 10 to 25 weeks of age. Metabolic and renal functions were assessed; the kidney was removed for histological analysis of glomerulosclerosis and expression of pro-inflammatory/fibrotic markers (RT-PCR and Western blotting; and the aorta was removed for studies of endothelium-dependent relaxation (EDR. FINDINGS: Hyperinsulinemic ZDF rats typically developed signs of type-2 diabetes and renovascular damage, as evidenced by albuminuria, glomerulosclerosis, and impaired EDR. Neither NWT-03 nor VIL improved metabolic parameters; for VIL, this was despite a 5-fold increase in glucagon-like peptide (GLP-1 levels. NWT-03 and VIL both reduced renal interleukin (Il-1β/Il-13 mRNA expression and glomerulosclerosis. However, only NWT-03 additionally decreased renal tumor necrosis factor (TNF-α mRNA and P22(phox protein expression, reduced albuminuria, and restored aortic EDR. Indomethacin added to the organ bath instantly improved aortic EDR, indicating a role for cyclooxygenase (COX-derived contractile prostanoids in opposing relaxation in ZDF rats. This indomethacin effect was reduced by NWT-03, but not by VIL, and coincided with decreased renal COX-1/2 protein expression. CONCLUSION AND INTERPRETATION: Long-term supplementation with the egg protein hydrolysate NWT-03 attenuated renovascular damage in this preclinical rat model of type 2 diabetes. A comparison to the DPP4-inhibitor VIL suggests that the effects of NWT-03 were related to both

The cardiovascular safety trials of DPP-4 inhibitors, GLP-1 agonists, and SGLT2 inhibitors.

Science.gov (United States)

Secrest, Matthew H; Udell, Jacob A; Filion, Kristian B

2017-04-01

In this paper, we review the results of large, double-blind, placebo-controlled randomized trials mandated by the US Food and Drug Administration to examine the cardiovascular safety of newly-approved antihyperglycemic agents in patients with type 2 diabetes. The cardiovascular effects of dipeptidyl peptidase-4 (DPP-4) inhibitors remain controversial: while these drugs did not reduce or increase the risk of primary, pre-specified composite cardiovascular outcomes, one DPP-4 inhibitor (saxagliptin) increased the risk of hospitalization for heart failure in the overall population; another (alogliptin) demonstrated inconsistent effects on heart failure hospitalization across subgroups of patients, and a third (sitagliptin) demonstrated no effect on heart failure. Evidence for cardiovascular benefits of glucagon-like peptide-1 (GLP-1) agonists has been similarly heterogeneous, with liraglutide and semaglutide reducing the risk of composite cardiovascular outcomes, but lixisenatide having no reduction or increase in cardiovascular risk. The effect of GLP-1 agonists on retinopathy remains a potential concern. In the only completed trial to date to assess a sodium-glucose cotransporter-2 (SGLT2) inhibitor, empagliflozin reduced the risk of composite cardiovascular endpoints, predominantly through its impact on cardiovascular mortality and heart failure hospitalization. Copyright © 2017 Elsevier Inc. All rights reserved.

Characterization of a Decapentapletic Gene (AccDpp from Apis cerana cerana and Its Possible Involvement in Development and Response to Oxidative Stress.

Directory of Open Access Journals (Sweden)

Guilin Li

Full Text Available To tolerate many acute and chronic oxidative stress-producing agents that exist in the environment, organisms have evolved many classes of signal transduction pathways, including the transforming growth factor β (TGFβ signal pathway. Decapentapletic gene (Dpp belongs to the TGFβ superfamily, and studies on Dpp have mainly focused on its role in the regulation of development. No study has investigated the response of Dpp to oxidative pressure in any organism, including Apis cerana cerana (A. cerana cerana. In this study, we identified a Dpp gene from A. cerana cerana named AccDpp. The 5΄ flanking region of AccDpp had many transcription factor binding sites that relevant to development and stress response. AccDpp was expressed at all stages of A. cerana cerana, with its highest expression in 15-day worker bees. The mRNA level of AccDpp was higher in the poison gland and midgut than other tissues. Furthermore, the transcription of AccDpp could be repressed by 4°C and UV, but induced by other treatments, according to our qRT-PCR analysis. It is worth noting that the expression level of AccDpp protein was increased after a certain time when A. cerana cerana was subjected to all simulative oxidative stresses, a finding that was not completely consistent with the result from qRT-PCR. It is interesting that recombinant AccDpp restrained the growth of Escherichia coli, a function that might account for the role of the antimicrobial peptides of AccDpp. In conclusion, these results provide evidence that AccDpp might be implicated in the regulation of development and the response of oxidative pressure. The findings may lay a theoretical foundation for further genetic studies of Dpp.

32 CFR 728.44 - Members of security assistance training programs, foreign military sales, and their ITO...

Science.gov (United States)

2010-07-01

..., foreign military sales, and their ITO authorized dependents. 728.44 Section 728.44 National Defense... § 728.44 Members of security assistance training programs, foreign military sales, and their ITO... patient is an ITO authorized dependent), grade or rate, country of origin, diagnosis, type of elective...

A comparison of effects of DPP-4 inhibitor and SGLT2 inhibitor on lipid profile in patients with type 2 diabetes.

Science.gov (United States)

Cha, Seon-Ah; Park, Yong-Moon; Yun, Jae-Seung; Lim, Tae-Seok; Song, Ki-Ho; Yoo, Ki-Dong; Ahn, Yu-Bae; Ko, Seung-Hyun

2017-04-13

Previous studies suggest that dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium glucose cotransporter 2 (SGLT2) inhibitors have different effects on the lipid profile in patients with type 2 diabetes. We investigated the effects of DPP-4 inhibitors and SGLT2 inhibitors on the lipid profile in patients with type 2 diabetes. From January 2013 to December 2015, a total of 228 patients with type 2 diabetes who were receiving a DPP-4 inhibitor or SGLT2 inhibitor as add-on therapy to metformin and/or a sulfonylurea were consecutively enrolled. We compared the effects of DPP-4 inhibitors and SGLT2 inhibitors on the lipid profile at baseline and after 24 weeks of treatment. To compare lipid parameters between the two groups, we used the analysis of covariance (ANCOVA). A total of 184 patients completed follow-up (mean age: 53.1 ± 6.9 years, mean duration of diabetes: 7.1 ± 5.7 years). From baseline to 24 weeks, HDL-cholesterol (HDL-C) levels were increased by 0.5 (95% CI, -0.9 to 2.0) mg/dl with a DPP-4 inhibitor and by 5.1 (95% CI, 3.0 to 7.1) mg/dl with an SGLT2 inhibitor (p = 0.001). LDL-cholesterol (LDL-C) levels were reduced by 8.4 (95% CI, -14.0 to -2.8) mg/dl with a DPP-4 inhibitor, but increased by 1.3 (95% CI, -5.1 to 7.6) mg/dl with an SGLT2 inhibitor (p = 0.046). There was no significant difference in the mean hemoglobin A1c (8.3 ± 1.1 vs. 8.0 ± 0.9%, p = 0.110) and in the change of total cholesterol (TC) (p = 0.836), triglyceride (TG) (p = 0.867), apolipoprotein A (p = 0.726), apolipoprotein B (p = 0.660), and lipoprotein (a) (p = 0.991) between the DPP-4 inhibitor and the SGLT2 inhibitor. The SGLT2 inhibitor was associated with a significant increase in HDL-C and LDL-C after 24 weeks of SGLT2 inhibitor treatment in patients with type 2 diabetes compared with those with DPP-4 inhibitor treatment in this study. This study was conducted by retrospective medical record review.

Understanding SOL plasma turbulence by interchange motions

Czech Academy of Sciences Publication Activity Database

Horáček, Jan; Pitts, R. A.; Nielsen, A.H.; Garcia, O.E.

2007-01-01

Roč. 52, č. 16 (2007), s. 192-193 ISSN 0003-0503. [Annual meeting of the division of plasma physics/49th./. Orlando , 12.11.2007-16.11.2007] Grant - others:-(XE) European Training fellowships and Grants (Euratom), EDGETURB Institutional research plan: CEZ:AV0Z20430508 Keywords : tokamak * plasma * scrape-off layer * turbulence * interchange instability Subject RIV: BL - Plasma and Gas Discharge Physics http://meetings.aps.org/Meeting/DPP07/Event/70125

The Dipeptidyl Peptidases 4, 8, and 9 in Mouse Monocytes and Macrophages: DPP8/9 Inhibition Attenuates M1 Macrophage Activation in Mice.

Science.gov (United States)

Waumans, Yannick; Vliegen, Gwendolyn; Maes, Lynn; Rombouts, Miche; Declerck, Ken; Van Der Veken, Pieter; Vanden Berghe, Wim; De Meyer, Guido R Y; Schrijvers, Dorien; De Meester, Ingrid

2016-02-01

Atherosclerosis remains the leading cause of death in Western countries. Dipeptidyl peptidase (DPP) 4 has emerged as a novel target for the prevention and treatment of atherosclerosis. Family members DPP8 and 9 are abundantly present in macrophage-rich regions of atherosclerotic plaques, and DPP9 inhibition attenuates activation of human M1 macrophages in vitro. Studying this family in a mouse model for atherosclerosis would greatly advance our knowledge regarding their potential as therapeutic targets. We found that DPP4 is downregulated during mouse monocyte-to-macrophage differentiation. DPP8 and 9 expression seems relatively low in mouse monocytes and macrophages. Viability of primary mouse macrophages is unaffected by DPP4 or DPP8/9 inhibition. Importantly, DPP8/9 inhibition attenuates macrophage activation as IL-6 secretion is significantly decreased. Mouse macrophages respond similarly to DPP inhibition, compared to human macrophages. This shows that the mouse could become a valid model species for the study of DPPs as therapeutic targets in atherosclerosis.

Measurements of Electron Temperature and Density Profiles of Plasmas Produced by Nike KrF Laser for Laser Plasma Instability (LPI) Research

Science.gov (United States)

Oh, Jaechul; Weaver, J. L.; Obenschain, S. P.; Schmitt, A. J.; Kehne, D. M.; Karasik, M.; Chan, L.-Y.; Serlin, V.; Phillips, L.

2012-10-01

ExperimentsfootnotetextJ. Oh, et al, GO5.4, APS DPP (2010).^,footnotetextJ. L. Weaver, et al, GO5.3, APS DPP (2010). using Nike KrF laser observed LPI signatures from CH plasmas at the laser intensities above ˜1x10^15 W/cm^2. Knowing spatial profiles of temperature (Te) and density (ne) in the underdense coronal region (0 Nike LPI experiment, a side-on grid imaging refractometer (GIR)footnotetextR. S. Craxton, et al, Phys. Fluids B 5, 4419 (1993). is being deployed for measuring the underdense plasma profiles. The GIR will resolve Te and ne in space taking a 2D snapshot of probe laser (λ= 263 nm, δt = 10 psec) beamlets (50μm spacing) refracted by the plasma at a selected time during the laser illumination. Time-resolved spectrometers with an absolute-intensity-calibrated photodiode array and a streak camera will simultaneously monitor light emission from the plasma in spectral ranges relevant to Raman (SRS) and two plasmon decay (TDP) instabilities. The experimental study of effects of the plasma profiles on the LPI initiation will be presented.

30 CFR 250.251 - If I propose activities in the Alaska OCS Region, what planning information must accompany the DPP?

Science.gov (United States)

2010-07-01

... Region, what planning information must accompany the DPP? 250.251 Section 250.251 Mineral Resources... Region, what planning information must accompany the DPP? If you propose development and production activities in the Alaska OCS Region, the following planning information must accompany your DPP: (a...

INTERACTION OF LASER RADIATION WITH MATTER. LASER PLASMA High-power EUV (13.5 nm) light source

Science.gov (United States)

Borisov, Vladimir M.; Borisova, Galina N.; Vinokhodov, Aleksandr Yu; Zakharov, S. V.; Ivanov, Aleksandr S.; Kiryukhin, Yurii B.; Mishchenko, Valentin A.; Prokof'ev, Aleksandr V.; Khristoforov, Oleg B.

2010-10-01

Characteristics of a discharge-produced plasma (DPP) light source in the spectral band 13.5±0.135 nm, developed for Extreme Ultra Violet (EUV) lithography, are presented. EUV light is generated by DPP in tin vapour formed between rotating disk electrodes. The discharge is ignited by a focused laser beam. The EUV power 1000 W/(2π sr) in the spectral band 13.5±0.135 nm was achieved with input power about of ~63 kW to the plasma at a pulse repetition rate ~7 kHz . The results of numerical simulation are compared with the experimental data.

Discovery of DPP IV inhibitors by pharmacophore modeling and QSAR analysis followed by in silico screening.

Science.gov (United States)

Al-Masri, Ihab M; Mohammad, Mohammad K; Taha, Mutasem O

2008-11-01

Dipeptidyl peptidase IV (DPP IV) deactivates the natural hypoglycemic incretin hormones. Inhibition of this enzyme should restore glucose homeostasis in diabetic patients making it an attractive target for the development of new antidiabetic drugs. With this in mind, the pharmacophoric space of DPP IV was explored using a set of 358 known inhibitors. Thereafter, genetic algorithm and multiple linear regression analysis were employed to select an optimal combination of pharmacophoric models and physicochemical descriptors that yield selfconsistent and predictive quantitative structure-activity relationships (QSAR) (r(2) (287)=0.74, F-statistic=44.5, r(2) (BS)=0.74, r(2) (LOO)=0.69, r(2) (PRESS) against 71 external testing inhibitors=0.51). Two orthogonal pharmacophores (of cross-correlation r(2)=0.23) emerged in the QSAR equation suggesting the existence of at least two distinct binding modes accessible to ligands within the DPP IV binding pocket. Docking experiments supported the binding modes suggested by QSAR/pharmacophore analyses. The validity of the QSAR equation and the associated pharmacophore models were established by the identification of new low-micromolar anti-DPP IV leads retrieved by in silico screening. One of our interesting potent anti-DPP IV hits is the fluoroquinolone gemifloxacin (IC(50)=1.12 muM). The fact that gemifloxacin was recently reported to potently inhibit the prodiabetic target glycogen synthase kinase 3beta (GSK-3beta) suggests that gemifloxacin is an excellent lead for the development of novel dual antidiabetic inhibitors against DPP IV and GSK-3beta.

Soluble DPP-4 up-regulates toll-like receptors and augments inflammatory reactions, which are ameliorated by vildagliptin or mannose-6-phosphate.

Science.gov (United States)

Lee, Dong-Sung; Lee, Eun-Sol; Alam, Md Morshedul; Jang, Jun-Hyeog; Lee, Ho-Sub; Oh, Hyuncheol; Kim, Youn-Chul; Manzoor, Zahid; Koh, Young-Sang; Kang, Dae-Gil; Lee, Dae Ho

2016-02-01

Studies have shown that dipeptidyl peptidase-4 (DPP-4) inhibitors have anti-inflammatory effects. Soluble DPP-4 (sDPP-4) has been considered as an adipokine of which actions need to be further characterized. We investigated the pro-inflammatory actions of sDPP-4 and the anti-inflammatory effects of DPP-4 inhibition, using vildagliptin, as an enzymatic inhibitor, and mannose-6-phosphate (M6P) as a competitive binding inhibitor. In lipopolysaccharide (LPS)-stimulated RAW264.7 cells, vildagliptin suppressed the increased expression of inducible nitric oxide synthase (iNOS) and phosphorylated JNK (pJNK), activation of the NF-κB pathway, and the resultant NO and proinflammatory cytokine production. Although sDPP-4 alone did not affect the protein level of iNOS or pJNK or the production of NO in RAW264.7 cells, it did amplify iNOS expression, NO responses, and proinflammatory cytokine production in LPS-stimulated RAW264 cells. As a probable mechanism, we found that sDPP-4 caused dose-dependent increases in the expression levels of toll-like receptor 4 (TLR4) and TLR2 in RAW264.7 cells, and that these alterations were inhibited by vildagliptin, M6P, or bisindolylmaleimide II, a protein kinase C inhibitor. Either vildagliptin or M6P suppressed iNOS expression and NO and cytokine production in LPS+DPP-4-co-stimulated macrophages, while combined treatment of the co-stimulated cells with both agents had increased anti-inflammatory effects compared with either treatment alone. Intravenous injection of sDPP-4 to C57BL/6J mice increased the expression of both TLRs in kidney and white adipose tissues. Our findings suggest that sDPP-4 enhances inflammatory actions via TLR pathway, while DPP-4 inhibition with either an enzymatic or binding inhibitor has anti-inflammatory effects. Copyright © 2015 Elsevier Inc. All rights reserved.

Lower dipeptidyl peptidase-4 following exercise training plus weight loss is related to increased insulin sensitivity in adults with metabolic syndrome.

Science.gov (United States)

Malin, Steven K; Huang, Hazel; Mulya, Anny; Kashyap, Sangeeta R; Kirwan, John P

2013-09-01

Dipeptidyl peptidase-4 (DPP-4) is a circulating glycoprotein that impairs insulin-stimulated glucose uptake and is linked to obesity and metabolic syndrome. However, the effect of exercise on plasma DPP-4 in adults with metabolic syndrome is unknown. Therefore, we determined the effect of exercise on DPP-4 and its role in explaining exercise-induced improvements in insulin sensitivity. Fourteen obese adults (67.9±1.2 years, BMI: 34.2±1.1kg/m(2)) with metabolic syndrome (ATP III criteria) underwent a 12-week supervised exercise intervention (60min/day for 5 days/week at ∼85% HRmax). Plasma DPP-4 was analyzed using an enzyme-linked immunosorbent assay. Insulin sensitivity was measured using the euglycemic-hyperinsulinemic clamp (40mU/m(2)/min) and estimated by HOMA-IR. Visceral fat (computerized tomography), 2-h glucose levels (75g oral glucose tolerance), and basal fat oxidation as well as aerobic fitness (indirect calorimetry) were also determined before and after exercise. The intervention reduced visceral fat, lowered blood pressure, glucose and lipids, and increased aerobic fitness (PExercise improved clamp-derived insulin sensitivity by 75% (PExercise training reduces plasma DPP-4, which may be linked to elevated insulin sensitivity and fat oxidation. Maintaining low plasma DPP-4 concentrations is a potential mechanism whereby exercise plus weight loss prevents/delays the onset of type 2 diabetes in adults with metabolic syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

Discovery of Novel Tricyclic Heterocycles as Potent and Selective DPP-4 Inhibitors for the Treatment of Type 2 Diabetes

Energy Technology Data Exchange (ETDEWEB)

Wu, Wen-Lian; Hao, Jinsong; Domalski, Martin; Burnett, Duane A.; Pissarnitski, Dmitri; Zhao, Zhiqiang; Stamford, Andrew; Scapin, Giovanna; Gao, Ying-Duo; Soriano, Aileen; Kelly, Terri M.; Yao, Zuliang; Powles, Mary Ann; Chen, Shiying; Mei, Hong; Hwa, Joyce (Merck)

2016-05-12

In our efforts to develop second generation DPP-4 inhibitors, we endeavored to identify distinct structures with long-acting (once weekly) potential. Taking advantage of X-ray cocrystal structures of sitagliptin and other DPP-4 inhibitors, such as alogliptin and linagliptin bound to DPP-4, and aided by molecular modeling, we designed several series of heterocyclic compounds as initial targets. During their synthesis, an unexpected chemical transformation provided a novel tricyclic scaffold that was beyond our original design. Capitalizing on this serendipitous discovery, we have elaborated this scaffold into a very potent and selective DPP-4 inhibitor lead series, as highlighted by compound 17c.

Purification, identification and molecular mechanism of two dipeptidyl peptidase IV (DPP-IV) inhibitory peptides from Antarctic krill (Euphausia superba) protein hydrolysate.

Science.gov (United States)

Ji, Wei; Zhang, Chaohua; Ji, Hongwu

2017-10-01

Dipeptidyl peptidase IV (DPP-IV) played an important role in blood glucose regulation. Inhibition of DPP-IV may improve glycemic control in diabetics by preventing the rapid breakdown of incretin hormones and prolonging their physiological action. In this study, Antarctic krill (Euphausia superba) protein was hydrolyzed using animal proteolytic enzymes. The hydrolysate was purified sequentially by ultrafiltration, gel filtration chromatography and reversed phase high-performance liquid chromatography (RP-HPLC). DPP-IV inhibitory activity of the fractions achieved from Antarctic krill protein was determined by DPP-IV screening reagent kit. Two purified peptides were identified by Xevo G2-XS QTof mass spectrometer (QTOF-MS). One peptide purified was Ala-Pro (AP) with IC 50 values of 0.0530mg/mL, the other Ile-Pro-Ala (IPA) with IC 50 values of 0.0370mg/mL. They both exhibited strong DPP-IV inhibitory activity. The molecular docking analysis revealed that DPP-IV inhibition by AP and IPA was mainly due to formation of a strong interaction surface force with the 91-96 and 101-105 amino acids of the DPP-IV. Our results suggested that the protein hydrolysate from Antarctic krill can be considered as a promising natural source of DPP-IV inhibitory peptides in the management of diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical trial simulation methods for estimating the impact of DPP-4 inhibitors on cardiovascular disease

Directory of Open Access Journals (Sweden)

Schuetz CA

2015-06-01

Full Text Available Charles Andy Schuetz,1 Siew Hwa Ong,2 Matthias Blüher3 1Evidera Inc., Bethesda, MD, USA; 2Novartis Pharma AG, Basel, Switzerland; 3Department of Medicine, University of Leipzig, Leipzig, Germany Introduction: Dipeptidyl peptidase-4 (DPP-4 inhibitors are a class of oral antidiabetic agents for the treatment of type 2 diabetes mellitus, which lower blood glucose without causing severe hypoglycemia. However, the first cardiovascular (CV safety trials have only recently reported their results, and our understanding of these therapies remains incomplete. Using clinical trial simulations, we estimated the effectiveness of DPP-4 inhibitors in preventing major adverse cardiovascular events (MACE in a population like that enrolled in the SAVOR-TIMI (the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus – Thrombolysis in Myocardial Infarction 53 trial. Methods: We used the Archimedes Model to simulate a clinical trial of individuals (N=11,000 with diagnosed type 2 diabetes and elevated CV risk, based on established disease or multiple risk factors. The DPP-4 class was modeled with a meta-analysis of HbA1c and weight change, pooling results from published trials of alogliptin, linagliptin, saxagliptin, sitagliptin, and vildagliptin. The study treatments were added-on to standard care, and outcomes were tracked for 20 years. Results: The DPP-4 class was associated with an HbA1c drop of 0.66% (0.71%, 0.62% and a weight drop of 0.14 (-0.07, 0.36 kg. These biomarker improvements produced a relative risk (RR for MACE at 5 years of 0.977 (0.968, 0.986. The number needed to treat to prevent one occurrence of MACE at 5 years was 327 (233, 550 in the elevated CV risk population. Conclusion: Consistent with recent trial publications, our analysis indicates that DPP-4 inhibitors do not increase the risk of MACE relative to the standard of care. This study provides insights about the long-term benefits of DPP-4 inhibitors and

32 CFR 728.12 - Extent of care.

Science.gov (United States)

2010-07-01

... § 728.12 Extent of care. Members who are away from their duty stations or are on duty where there is no... providing authorization for non-Federal care at DHHS expense. (b) Maternity episode for active duty female... facilities (once the mother has been admitted to the USMTF) from funds available for care of active duty...

32 CFR 728.73 - Applicants for enlistment or reenlistment in the Armed Forces, and applicants for enlistment in...

Science.gov (United States)

2010-07-01

... 32 National Defense 5 2010-07-01 2010-07-01 false Applicants for enlistment or reenlistment in the Armed Forces, and applicants for enlistment in the reserve components. 728.73 Section 728.73 National... ELIGIBLE PERSONS AT NAVY MEDICAL DEPARTMENT FACILITIES Other Persons § 728.73 Applicants for enlistment or...

Sex differences in apolipoprotein A1 and nevirapine-induced toxicity

OpenAIRE

Aline Marinho; Clara Dias; Alexandra Antunes; Umbelina Caixas; Teresa Branco; Matilde Marques; Emília Monteiro; Sofia Pereira

2014-01-01

Nevirapine (NVP) is associated with severe liver and skin toxicity through sulfotransferase (SULT) bioactivation of the phase I metabolite 12-hydroxy-NVP [1–3]. The female sex, a well-known risk factor for NVP-induced toxicity, is associated with higher SULT expression [4] and lower plasma levels of 12-hydroxy-NVP [3]. Interestingly, apolipoprotein A1 (ApoA1) increases SULT2B1 activity and ApoA1 synthesis is increased by NVP [5, 6]. Herein, we explore the effect of ApoA1 levels on NVP metabol...

Reduced energy conservation law for magnetized plasma

International Nuclear Information System (INIS)

Sosenko, P.P.; Decyk, V.K.

1994-01-01

A global energy conservation law for a magnetized plasma is studied within the context of a quasiparticle description. A reduced energy conservation law is derived for low-frequency, as compared to the gyromagnetic frequency, plasma motions with regard to both non-uniform mean flows and fluctuations in the plasma. The mean value of plasma energy is calculated and sufficient stability conditions for non-equilibrium plasmas are derived. (orig.)

Crystallization and preliminary X-ray diffraction studies of the putative haloalkane dehalogenase DppA from Plesiocystis pacifica SIR-I

International Nuclear Information System (INIS)

Bogdanović, Xenia; Hesseler, Martin; Palm, Gottfried J.; Bornscheuer, Uwe T.; Hinrichs, Winfried

2010-01-01

The crystallization and preliminary X-ray diffraction studies of DppA from P. pacifica SIR-I are reported. DppA from Plesiocystis pacifica SIR-I is a putative haloalkane dehalogenase (EC 3.8.1.5) and probably catalyzes the conversion of halogenated alkanes to the corresponding alcohols. The enzyme was expressed in Escherichia coli BL21 and purified to homogeneity by ammonium sulfate precipitation and reversed-phase and ion-exchange chromatography. The DppA protein was crystallized by the vapour-diffusion method and protein crystals suitable for data collection were obtained in the orthorhombic space group P2 1 2 1 2. The DppA crystal diffracted X-rays to 1.9 Å resolution using an in-house X-ray generator

Pharmacovigilance Evaluation of the Association Between DPP-4 Inhibitors and Heart Failure: Stimulated Reporting and Moderation by Drug Interactions.

Science.gov (United States)

Fadini, Gian Paolo; Sarangdhar, Mayur; Avogaro, Angelo

2018-04-01

In the SAVOR-TIMI trial, the risk of heart failure (HF) was increased by 27% in T2D patients randomized to the dipeptidyl peptidase-4 inhibitor (DPP4i) saxagliptin. Other studies have provided inconsistent results regarding this association. Herein, we performed a pharmacovigilance analysis of the rate of HF associated with DPP4is, focusing on stimulated reporting and moderation by drug-drug interactions. We mined the FDA adverse event (AE) reporting system (FAERS) from 2004q1 to 2017q3, including a total of 9906,642 AE reports. Rates (/1000 reports) of HF within the reports for DPP4is and reports for other antidiabetic drugs were calculated for the period up to 2013q3 (date of publication of the SAVOR-TIMI trial results) and from 2013q4 to 2017q3. Analyses were refined by filtering according to therapeutic area, concomitant diseases and drugs, and competing AEs. The rate of HF among the AE reports filed for DPP4is significantly increased after 2013q3, especially for saxagliptin. When compared to non-insulin non-glitazone antidiabetic drugs, the proportional reporting ratio (PRR) of HF for DPP4is was 0.62 (95% CI 0.56-0.68) up to 2013q3 and 2.12 (95% CI 1.96-2.28) from 2013q4 to 2017q3. This stimulated reporting was consistent in subanalyses based on the presence/absence of cardiac disorders and after controlling for competing AEs. The rate of HF among AE reports for DPP4is was modestly moderated by the concomitant use of metformin (- 15%) and strongly moderated by the concomitant use of SGLT2 inhibitors (- 63%), even after excluding competing AEs. Within the FAERS, the association between HF and DPP4is was biased by stimulated reporting, implying that the publication of the SAVOR-TIMI trial and the subsequent regulatory warnings primed clinicians to report HF events in DPP4i users as drug-related AEs. The rate of HF associated with DPP4is was moderated when they were used in combination with SGLT2 inhibitors.

Combination therapy with DPP-4 inhibitors and pioglitazone in type 2 diabetes: theoretical consideration and therapeutic potential

Directory of Open Access Journals (Sweden)

Nasser Mikhail

2008-12-01

Full Text Available Nasser MikhailEndocrinology Division, Olive View-UCLA Medical Center, David-Geffen School of Medicine, CA, USAAbstract: Sitagliptin and vildagliptin represent a new class of anti-diabetic agents that enhance the action of incretin hormones through inhibition of dipeptidyl peptidase-4 (DPP-4, the enzyme that normally inactivates incretin hormones. Because of their distinct mechanism of action, DPP-4 inhibitors can be used as add-on therapy to other classes of drugs for treatment of type 2 diabetes. The objective of this review is to critically evaluate clinical trials of sitagliptin and vildagliptin in combination with pioglitazone. The addition of either sitagliptin or vildagliptin to ongoing pioglitazone therapy is associated with reduction in average hemoglobin A1c (HbA1c levels of approximately 0.7% compared with placebo and 1% compared with baseline after 24 weeks. When started concomitantly in drug-naïve patients, the combination of pioglitazone 30 mg and vildagliptin 100 mg qd reduces HbA1c by 1.9% after 24 weeks, compared with 1.1% with pioglitazone monotherapy. In general, the addition of DPP-4 inhibitors to pioglitazone was well tolerated, did not increase the incidence of hypoglycemia, and did not substantially worsen the weight-gain induced by pioglitazone. The combination of sitagliptpin or vildagliptin with pioglitazone can be a useful therapeutic approach in patients with type 2 diabetes who cannot tolerate metformin or a sulfonylurea.Keywords: incretins, sitagliptin, vildagliptin, dipeptidyl peptidase inhibitors, pioglitazone, type 2 diabetes

32 CFR 728.3 - General restrictions and priorities.

Science.gov (United States)

2010-07-01

... AND DENTAL CARE FOR ELIGIBLE PERSONS AT NAVY MEDICAL DEPARTMENT FACILITIES General § 728.3 General... domiciliary care. Routine dental care, other than dental prosthesis or orthodontia, may be rendered on a space...) Priorities. When care cannot be rendered to all eligible beneficiaries, the priorities in the following chart...

Cultural adaptation of a peer-led lifestyle intervention program for diabetes prevention in India: the Kerala diabetes prevention program (K-DPP).

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Mathews, Elezebeth; Thomas, Emma; Absetz, Pilvikki; D'Esposito, Fabrizio; Aziz, Zahra; Balachandran, Sajitha; Daivadanam, Meena; Thankappan, Kavumpurathu Raman; Oldenburg, Brian

2018-01-04

Type 2 diabetes mellitus (T2DM) is now one of the leading causes of disease-related deaths globally. India has the world's second largest number of individuals living with diabetes. Lifestyle change has been proven to be an effective means by which to reduce risk of T2DM and a number of "real world" diabetes prevention trials have been undertaken in high income countries. However, systematic efforts to adapt such interventions for T2DM prevention in low- and middle-income countries have been very limited to date. This research-to-action gap is now widely recognised as a major challenge to the prevention and control of diabetes. Reducing the gap is associated with reductions in morbidity and mortality and reduced health care costs. The aim of this article is to describe the adaptation, development and refinement of diabetes prevention programs from the USA, Finland and Australia to the State of Kerala, India. The Kerala Diabetes Prevention Program (K-DPP) was adapted to Kerala, India from evidence-based lifestyle interventions implemented in high income countries, namely, Finland, United States and Australia. The adaptation process was undertaken in five phases: 1) needs assessment; 2) formulation of program objectives; 3) program adaptation and development; 4) piloting of the program and its delivery; and 5) program refinement and active implementation. The resulting program, K-DPP, includes four key components: 1) a group-based peer support program for participants; 2) a peer-leader training and support program for lay people to lead the groups; 3) resource materials; and 4) strategies to stimulate broader community engagement. The systematic approach to adaptation was underpinned by evidence-based behavior change techniques. K-DPP is the first well evaluated community-based, peer-led diabetes prevention program in India. Future refinement and utilization of this approach will promote translation of K-DPP to other contexts and population groups within India as

30 CFR 250.244 - What geological and geophysical (G&G) information must accompany the DPP or DOCD?

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What geological and geophysical (G&G... Operations Coordination Documents (docd) § 250.244 What geological and geophysical (G&G) information must accompany the DPP or DOCD? The following G&G information must accompany your DPP or DOCD: (a) Geological...

Teneligliptin: a DPP-4 inhibitor for the treatment of type 2 diabetes

Directory of Open Access Journals (Sweden)

Kishimoto M

2013-05-01

Full Text Available Miyako KishimotoDepartment of Diabetes and Metabolic Medicine, Center Hospital, Tokyo, Japan; Diabetes and Metabolism Information Center, Diabetes Research Center, National Center for Global Health and Medicine, Tokyo, JapanAbstract: Dipeptidyl peptidase-4 (DPP-4 inhibitors have recently emerged as a new class of antidiabetic that show favorable results in improving glycemic control with a minimal risk of hypoglycemia and weight gain. Teneligliptin, a novel DPP-4 inhibitor, exhibits a unique structure characterized by five consecutive rings, which produce a potent and long-lasting effect. Teneligliptin is currently used in cases showing insufficient improvement in glycemic control even after diet control and exercise or a combination of diet control, exercise, and sulfonylurea- or thiazolidine-class drugs. In adults, teneligliptin is orally administered at a dosage of 20 mg once daily, which can be increased up to 40 mg per day. Because the metabolites of this drug are eliminated via renal and hepatic excretion, no dose adjustment is necessary in patients with renal impairment. The safety profile of teneligliptin is similar to those of other available DPP-4 inhibitors. However, caution needs to be exercised when administering teneligliptin to patients who are prone to QT prolongation. One study has reported that the postprandial blood glucose-lowering effects of teneligliptin administered prior to breakfast were sustained throughout the day, and the effects observed after dinner were similar to those observed after breakfast or lunch. Thus, although clinical data for this new drug are limited, this drug shows promise in stabilizing glycemic fluctuations throughout the day and consequently suppressing the progression of diabetic complications. However, continued evaluation in long-term studies and clinical trials is required to evaluate the efficacy and safety of the drug as well as to identify additional indications for its clinical use

Triplet State Formation in Photovoltaic Blends of DPP-Type Copolymers and PC71BM

KAUST Repository

Ochsmann, Julian R.

2015-04-29

The exciton dynamics in pristine films of two structurally related low-bandgap diketopyrrolopyrrole (DPP)-based donor–acceptor copolymers and the photophysical processes in bulk heterojunction solar cells using DPP copolymer:PC71BM blends are investigated by broadband transient absorption (TA) pump-probe experiments covering the vis–near-infrared spectral and fs–μs dynamic range. The experiments reveal surprisingly short exciton lifetimes in the pristine poly­mer films in conjunction with fast triplet state formation. An in-depth analysis of the TA data by multivariate curve resolution analysis shows that in blends with fullerene as acceptor ultrafast exciton dissociation creates charge carriers, which then rapidly recombine on the sub-ns timescale. Furthermore, at the carrier densities created by pulsed laser excitation the charge carrier recombination leads to a substantial population of the polymer triplet state. In fact, virtually quantitative formation of triplet states is observed on the sub-ns timescale. However, the quantitative triplet formation on the sub-ns timescale is not in line with the power conversion efficiencies of devices indicating that triplet state formation is an intensity-dependent process in these blends and is reduced under solar illumination conditions, as free charge carriers can be extracted from the photoactive layer in devices.

Increased radiosensitivity and radiothermosensitivity of human pancreatic MIA PaCa-2 and U251 glioblastoma cell lines treated with the novel Hsp90 inhibitor NVP-HSP990

International Nuclear Information System (INIS)

Milanović, Dušan; Firat, Elke; Grosu, Anca Ligia; Niedermann, Gabriele

2013-01-01

Heat shock Protein 90 (Hsp90) is a molecular chaperone that folds, stabilizes, and functionally regulates many cellular proteins involved in oncogenic signaling and in the regulation of radiosensitivity. It is upregulated in response to stress such a heat. Hyperthermia is a potent radiosensitizer, but induction of Hsp90 may potentially limit its efficacy. Our aim was to investigate whether the new Hsp90 inhibitor NVP-HSP990 increases radiosensitivity, thermosensitivity and radiothermosensitivity of human tumor cell lines. U251 glioblastoma and MIA PaCa-2 pancreatic carcinoma cells were used. To determine clonogenic survival, colony forming assays were performed. Cell viability and proliferation were assesed by Trypan blue staining. Cell cycle and apoptosis analyses were performed by flow cytometry. DAPI staining was used to detect mitotic catastrophe. NVP-HSP990 increased the thermosensitivity, radiosensitivity and radio-thermosensitivity of both cell lines in clonogenic assays. 72 hours after irradiation with 4 Gy, a significant reduction in cell number associated with considerable G2/M acumulation and mitotic catastrophe as well as cell death by apoptosis/necrosis was observed. Treatment with NVP-HSP990 strongly sensitized U251 and MIA PaCa-2 cells to hyperthermia and ionizing radiation or combination thereof through augmentation of G2/M arrest, mitotic catastrophe and associated apoptosis

The effects of GLP-1 analogues, DPP-4 inhibitors and SGLT2 inhibitors on the renal system.

Science.gov (United States)

Schernthaner, Guntram; Mogensen, Carl Erik; Schernthaner, Gerit-Holger

2014-09-01

Diabetic nephropathy (DN) affects an estimated 20%-40% of patients with type 2 diabetes mellitus (T2DM). Key modifiable risk factors for DN are albuminuria, anaemia, dyslipidaemia, hyperglycaemia and hypertension, together with lifestyle factors, such as smoking and obesity. Early detection and treatment of these risk factors can prevent DN or slow its progression, and may even induce remission in some patients. DN is generally preceded by albuminuria, which frequently remains elevated despite treatment in patients with T2DM. Optimal treatment and prevention of DN may require an early, intensive, multifactorial approach, tailored to simultaneously target all modifiable risk factors. Regular monitoring of renal function, including urinary albumin excretion, creatinine clearance and glomerular filtration rate, is critical for following any disease progression and making treatment adjustments. Dipeptidyl peptidase (DPP)-4 inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose levels without additional risk of hypoglycaemia, and may also reduce albuminuria. Further investigation of the potential renal benefits of DPP-4 and SGLT2 inhibitors is underway. © The Author(s) 2014.

Increased plasma dipeptidyl peptidase-4 activities are associated with high prevalence of subclinical atherosclerosis in Chinese patients with newly diagnosed type 2 diabetes: a cross-sectional study.

Science.gov (United States)

Zheng, T P; Liu, Y H; Yang, L X; Qin, S H; Liu, H B

2015-10-01

Hyperglycemia, insulin resistance, dislipidemia, oxidative stress and inflammation are well-documented risk factors for subclinical atherosclerosis. Dipeptidyl peptidase-4(DPP4) is a newly identified adipokine related to these risk factors. Hence, we aimed to investigate the association between plasma DPP4 activities and subclinical atherosclerosis in type 2 diabetes. A total of 985 newly diagnosed type 2 diabetic subjects were studied. Plasma DPP4 activity, mannose 6-phosphate receptor (M6P-R), oxidative stress parameters, inflammatory markers and common carotid artery Intima-Media Thickness (c-IMT) were measured in all participants. Participants in the highest quartile of DPP4 activity had higher HbA1c, homeostatic model assessment of insulin resistance(HOMA-IR), triglyceride, low-density lipoprotein cholesterol(LDL-C), oxidized LDL, nitrotyrosine, 8-iso-PGF2a, interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), M6P-R, c-IMT compared with participants in the lowest quartile (all P dislipidemia, oxidative stress and inflammation were higher with increasing DPP4 quartiles (P < 0.001 for trend). In the highest DPP4 quartile, subclinical atherosclerosis risk was significantly higher (OR 4.97; 95% CI 3.03-8.17) than in the lowest quartile. This association remained strong (2.17; 1.21-3.89) after further controlling for HbA1c, HOMA-IR, triglyceride, oxidized LDL, nitrotyrosine, and IL-6. This study shows that increased DPP4 activities are positively and independently associated with subclinical atherosclerosis in type 2 diabetes. Our findings suggest of potential role of DPP4 in the pathogenesis of subclinical atherosclerosis and in the prevention and management of this disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

In vitro assessment of competitive and time-dependent inhibition of the nevirapine metabolism by nortriptyline in rats.

Science.gov (United States)

Usach, Iris; Ferrer, José-Maria; Peris, José-Esteban

2018-04-17

Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1) widely used as a component of High Active Antiretroviral Therapy (HAART) since it is inexpensive, readily absorbed after oral administration and non-teratogenic. In the present work, the mechanism of a previously described pharmacokinetic interaction between NVP and the antidepressant drug nortriptyline (NT) was studied using rat hepatic microsomes. The obtained results showed a competitive inhibition of the NVP metabolism by NT. The three main NVP metabolites (2-OH-NVP, 3-OH-NVP and 12-OH-NVP) where competitively inhibited with similar inhibitory constant values (K i  = 4.01, 3.97 and 4.40 μM, respectively). Time-dependent inhibition of the NVP metabolism was also detected, with a 2.5-fold reduction in the IC 50 values of NT for 2-, 3-, and 12-OH-NVP formation when NT was preincubated with the microsomal suspension in the presence of an NADPH-generating system. A concentration-dependent inhibition of the formation of NVP metabolites by the main NT metabolite (10-OH-NT) was also observed, however, the inhibitory potency of 10-OH-NT was much lower than that of the parent drug. The apparent hepatic intrinsic clearance of NVP determined in these in vitro experiments was used to predict the in vivo clearance of NVP using the "well-stirred" and the "parallel-tube" models, resulting in values close to those previously observed in vivo clearance. Finally, a good prediction of the increase in the plasma concentrations of NVP when co-administered with NT was obtained employing the inhibitory constant of NT determined in vitro and the estimated plasma concentration of NT entering the liver. Copyright © 2018. Published by Elsevier Inc.

Novel targeted approaches to treating biliary tract cancer: the dual epidermal growth factor receptor and ErbB-2 tyrosine kinase inhibitor NVP-AEE788 is more efficient than the epidermal growth factor receptor inhibitors gefitinib and erlotinib.

Science.gov (United States)

Wiedmann, Marcus; Feisthammel, Jürgen; Blüthner, Thilo; Tannapfel, Andrea; Kamenz, Thomas; Kluge, Annett; Mössner, Joachim; Caca, Karel

2006-08-01

cell lines. Gefitinib, erlotinib and NVP-AEE788 caused a significant growth inhibition in vitro; however, there was a significant difference in efficacy (NVP-AEE788>erlotinib>gefitinib). After 14 days of in-vivo treatment, using the chimeric mouse model, tumors had a significantly reduced volume and mass after NVP-AEE788, but not after erlotinib treatment, as compared with placebo. Reduction of proliferation (signalling via the mitogen-activated protein kinase pathway), induction of apoptosis and inhibition of angiogenesis were the main mechanisms of drug action. No significant reduction of anti-apoptotic AKT phosphorylation, however, occurred, which may be a possible counter mechanism of the tumor. Epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 expression was detectable in biliary tract cancer, and receptor inhibition exerts marked effects on tumor growth in vitro and in vivo, which was strongest for the dual EGFR/ErbB-2 inhibitor NVP-AEE788. Therefore, further clinical evaluation of this new drug for the treatment of biliary tract cancer is recommended.

Inhibitory potency of Withania somnifera extracts against DPP-4: an ...

African Journals Online (AJOL)

Materials and Methods: Young and matured fresh roots, leaves, and fruits of WS plant extract were considered and were systematically evaluated for DPP-4 inhibitory activity using in vitro method, enzyme kinetics, phytochemical analysis, RP-HPLC, LCMS and 1H and 13C NMR method and structure-activity relationship ...

Changes in glucose-induced plasma active glucagon-like peptide-1 levels by co-administration of sodium–glucose cotransporter inhibitors with dipeptidyl peptidase-4 inhibitors in rodents

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Takahiro Oguma

2016-12-01

Full Text Available We investigated whether structurally different sodium–glucose cotransporter (SGLT 2 inhibitors, when co-administered with dipeptidyl peptidase-4 (DPP4 inhibitors, could enhance glucagon-like peptide-1 (GLP-1 secretion during oral glucose tolerance tests (OGTTs in rodents. Three different SGLT inhibitors—1-(β-d-Glucopyranosyl-4-chloro-3-[5-(6-fluoro-2-pyridyl-2-thienylmethyl]benzene (GTB, TA-1887, and canagliflozin—were examined to assess the effect of chemical structure. Oral treatment with GTB plus a DPP4 inhibitor enhanced glucose-induced plasma active GLP-1 (aGLP-1 elevation and suppressed glucose excursions in both normal and diabetic rodents. In DPP4-deficient rats, GTB enhanced glucose-induced aGLP-1 elevation without affecting the basal level, whereas metformin, previously reported to enhance GLP-1 secretion, increased both the basal level and glucose-induced elevation. Oral treatment with canagliflozin and TA-1887 also enhanced glucose-induced aGLP-1 elevation when co-administered with either teneligliptin or sitagliptin. These data suggest that structurally different SGLT2 inhibitors enhance plasma aGLP-1 elevation and suppress glucose excursions during OGTT when co-administered with DPP4 inhibitors, regardless of the difference in chemical structure. Combination treatment with DPP4 inhibitors and SGLT2 inhibitors having moderate SGLT1 inhibitory activity may be a promising therapeutic option for improving glycemic control in patients with type 2 diabetes mellitus.

DPP-4 inhibitor treatment: β-cell response but not HbA1c reduction is dependent on the duration of diabetes

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Kozlovski P

2017-03-01

Full Text Available Plamen Kozlovski,1 Vaishali Bhosekar,2 James E Foley3 1Novartis Pharma AG, Basel, Switzerland; 2Novartis Healthcare Private Limited, Hyderabad, India; 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA Introduction: Dipeptidyl peptidase-4 (DPP-4 inhibitors reduce hyperglycemia in patients with type 2 diabetes mellitus (T2DM by enhancing insulin and suppressing glucagon secretion. Since T2DM is associated with progressive loss of β-cell function, we hypothesized that the DPP-4 inhibitor action to improve β-cell function would be attenuated with longer duration of T2DM.Methods: Data from six randomized, placebo-controlled trials of 24 weeks duration, where β-cell response to vildagliptin 50 mg twice daily was assessed, were pooled. In each study, the insulin secretory rate relative to glucose (ISR/G 0–2h during glucose load (standard meal or oral glucose tolerance test was assessed at baseline and end of study. The mean placebo-subtracted difference (PSD in the change in ISR/G 0–2h from baseline for each study was evaluated as a function of age, duration of T2DM, baseline ISR/G 0–2h, glycated hemoglobin (HbA1c, fasting plasma glucose, body mass index, and mean PSD in the change in HbA1c from baseline, using univariate model.Results: There was a strong negative association between the PSD in the change from baseline in ISR/G 0–2h and duration of T2DM (r= −0.89, p<0.02. However, there was no association between the PSD in the change from baseline in ISR/G 0–2h and the PSD in the change from baseline in HbA1c (r=0.33, p=0.52. None of the other characteristics were significantly associated with mean PSD change in ISR/G 0–2h.Conclusion: These findings indicate that the response of the β-cell, but not the HbA1c reduction, with vildagliptin is dependent on duration of T2DM. Further, it can be speculated that glucagon suppression may become the predominant mechanism via which glycemic control is improved when treatment with a

Effect of adding the novel fiber, PGX®, to commonly consumed foods on glycemic response, glycemic index and GRIP: a simple and effective strategy for reducing post prandial blood glucose levels - a randomized, controlled trial

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Lyon Michael

2010-11-01

Full Text Available Abstract Background Reductions in postprandial glycemia have been demonstrated previously with the addition of the novel viscous polysaccharide (NVP, PolyGlycopleX® (PGX®, to an OGTT or white bread. This study explores whether these reductions are sustained when NVP is added to a range of commonly consumed foods or incorporated into a breakfast cereal. Methods Ten healthy subjects (4M, 6F; age 37.3 ± 3.6 y; BMI 23.8 ± 1.3 kg/m2, participated in an acute, randomized controlled trial. The glycemic response to cornflakes, rice, yogurt, and a frozen dinner with and without 5 g of NVP sprinkled onto the food was determined. In addition, 3 granolas with different levels of NVP and 3 control white breads and one white bread and milk were also consumed. All meals contained 50 g of available carbohydrate. Capillary blood samples were taken fasting and at 15, 30, 45, 60, 90 and 120 min after the start of the meal. The glycemic index (GI and the glycemic reduction index potential (GRIP were calculated. The blood glucose concentrations at each time and the iAUC values were subjected to repeated-measures analysis of variance (ANOVA examining for the effect of test meal. After demonstration of significant heterogeneity, differences between individual means was assessed using GLM ANOVA with Tukey test to adjust for multiple comparisons. Results Addition of NVP reduced blood glucose response irrespective of food or dose (p Conclusion Sprinkling or incorporation of NVP into a variety of different foods is highly effective in reducing postprandial glycemia and lowering the GI of a food. Clinical Trial registration NCT00935350.

Dietary Wheat Bran Oil Is Equally as Effective as Rice Bran Oil in Reducing Plasma Cholesterol.

Science.gov (United States)

Lei, Lin; Chen, Jingnan; Liu, Yuwei; Wang, Lijun; Zhao, Guohua; Chen, Zhen-Yu

2018-03-21

Rice bran oil (RBO) possesses a plasma cholesterol-lowering activity, while effect of wheat bran oil (WBO) on plasma cholesterol remains unknown. The present study compared the cholesterol-lowering activity of WBO with that of RBO in hamsters. Fifty-four male hamsters were divided into seven groups fed either a noncholesterol diet (NCD) or one of six high-cholesterol diets, namely HCD diet (0.2% cholesterol +9.5% lard), HCD+C diet (0.2% cholesterol +9.5% lard +0.5% cholestyramine), WL diet (0.2% cholesterol +4.8% Lard +4.8% WBO), WH diet (0.2% cholesterol +9.5% WBO), RL diet (0.2% cholesterol +4.8% Lard +4.8% RBO), and RH diet (0.2% cholesterol +9.5% RBO). Plasma total cholesterol (TC) in HCD group was 327.4 ± 31.8 mg/dL, while plasma TC in two WBO and two RBO groups was 242.2 ± 20.8, 243.1 ± 31.7, 257.1 ± 16.3, and 243.4 ± 46.0 mg/dL, respectively, leading to a decrease in plasma TC by 22-26% ( P cholesterol-lowering potency was seen between WBO and RBO. Plasma cholesterol-lowering activity of WBO and RBO was accompanied by down-regulation of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase and fatty acid synthase, while up-regulation of cholesterol-7α-hydroxylase. WL, WH, RL, and RH diets increased the fecal excretion of total neutral sterols by 72.8%, 106.9%, 5.4%, and 36.8% ( P cholesterol absorption via down-regulation of intestinal Niemann-Pick C1 like 1 protein, acyl CoA:cholesterol acyltransferase 2, and ATP binding cassette transporter 5. In summary, WBO was equally effective as RBO in decreasing plasma cholesterol in hypercholesterolemia hamsters.

Enabling high-mobility, ambipolar charge-transport in a DPP-benzotriazole copolymer by side-chain engineering

DEFF Research Database (Denmark)

Gruber, Mathias; Jung, Seok-Heon; Schott, Sam

2015-01-01

In this article we discuss the synthesis of four new low band-gap co-polymers based on the diketopyrrolopyrrole (DPP) and benzotriazole (BTZ) monomer unit. We demonstrate that the BTZ unit allows for additional solubilizing side-chains on the co-monomer and show that the introduction of a linear...... side-chain on the DPP-unit leads to an increase in thin-film order and charge-carrier mobility if a sufficiently solubilizing, branched, side chain is attached to the BTZ. We compare two different synthetic routes, direct arylation and Suzuki-polycondensation, by a direct comparison of polymers...

Type 2 diabetes impairs odour detection, olfactory memory and olfactory neuroplasticity; effects partly reversed by the DPP-4 inhibitor Linagliptin.

Science.gov (United States)

Lietzau, Grazyna; Davidsson, William; Östenson, Claes-Göran; Chiazza, Fausto; Nathanson, David; Pintana, Hiranya; Skogsberg, Josefin; Klein, Thomas; Nyström, Thomas; Darsalia, Vladimer; Patrone, Cesare

2018-02-23

Recent data suggest that olfactory deficits could represent an early marker and a pathogenic mechanism at the basis of cognitive decline in type 2 diabetes (T2D). However, research is needed to further characterize olfactory deficits in diabetes, their relation to cognitive decline and underlying mechanisms.The aim of this study was to determine whether T2D impairs odour detection, olfactory memory as well as neuroplasticity in two major brain areas responsible for olfaction and odour coding: the main olfactory bulb (MOB) and the piriform cortex (PC), respectively. Dipeptidyl peptidase-4 inhibitors (DPP-4i) are clinically used T2D drugs exerting also beneficial effects in the brain. Therefore, we aimed to determine whether DPP-4i could reverse the potentially detrimental effects of T2D on the olfactory system.Non-diabetic Wistar and T2D Goto-Kakizaki rats, untreated or treated for 16 weeks with the DPP-4i linagliptin, were employed. Odour detection and olfactory memory were assessed by using the block, the habituation-dishabituation and the buried pellet tests. We assessed neuroplasticity in the MOB by quantifying adult neurogenesis and GABAergic inhibitory interneurons positive for calbindin, parvalbumin and carletinin. In the PC, neuroplasticity was assessed by quantifying the same populations of interneurons and a newly identified form of olfactory neuroplasticity mediated by post-mitotic doublecortin (DCX) + immature neurons.We show that T2D dramatically reduced odour detection and olfactory memory. Moreover, T2D decreased neurogenesis in the MOB, impaired the differentiation of DCX+ immature neurons in the PC and altered GABAergic interneurons protein expression in both olfactory areas. DPP-4i did not improve odour detection and olfactory memory. However, it normalized T2D-induced effects on neuroplasticity.The results provide new knowledge on the detrimental effects of T2D on the olfactory system. This knowledge could constitute essentials for

30 CFR 250.272 - If a State objects to the DPP's or DOCD's coastal zone consistency certification, what can I do?

Science.gov (United States)

2010-07-01

... coastal zone consistency certification, what can I do? 250.272 Section 250.272 Mineral Resources MINERALS... objects to the DPP's or DOCD's coastal zone consistency certification, what can I do? If an affected State objects to the coastal zone consistency certification accompanying your proposed or disapproved DPP or...

Comparison of the complete genome sequences of Pseudomonassyringae pv. syringae B728a and pv. tomato DC3000.

Energy Technology Data Exchange (ETDEWEB)

Feil, Helene; Feil, William S.; Chain, Patrick; Larimer, Frank; DiBartolo, Genevieve; Copeland, Alex; Lykidis, Athanasios; Trong,Stephen; Nolan, Matt; Goltsman, Eugene; Thiel, James; Malfatti,Stephanie; Loper, Joyce E.; Lapidus, Alla; Detter, John C.; Land, Miriam; Richardson, Paul M.; Kyrpides, Nikos C.; Ivanova, Natalia; Lindow, StevenE.

2005-04-01

The complete genomic sequence of Pseudomonas syringaepathovar syringae B728a (Pss B728a), has been determined and is comparedwith that of Pseudomonas syringae pv. tomato DC3000 (Pst DC3000). Thesetwo pathovars of this economically important species of plant pathogenicbacteria differ in host range and apparent patterns of interaction withplants, with Pss having a more pronounced epiphytic stage of growth andhigher abiotic stress tolerance and Pst DC3000 having a more pronouncedapoplastic growth habitat. The Pss B728a genome (6.1 megabases) containsa circular chromosome and no plasmid, whereas the Pst DC3000 genome is6.5 mbp in size, composed of a circular chromosome and two plasmids.While a high degree of similarity exists between the two sequencedPseudomonads, 976 protein-encoding genes are unique to Pss B728a whencompared to Pst DC3000, including large genomic islands likely tocontribute to virulence and host specificity. Over 375 repetitiveextragenic palindromic sequences (REPs) unique to Pss B728a when comparedto Pst DC3000 are widely distributed throughout the chromosome except in14 genomic islands, which generally had lower GC content than the genomeas a whole. Content of the genomic islands vary, with one containing aprophage and another the plasmid pKLC102 of P. aeruginosa PAO1. Among the976 genes of Pss B728a with no counterpart in Pst DC3000 are thoseencoding for syringopeptin (SP), syringomycin (SR), indole acetic acidbiosynthesis, arginine degradation, and production of ice nuclei. Thegenomic comparison suggests that several unique genes for Pss B728a suchas ectoine synthase, DNA repair, and antibiotic production may contributeto epiphytic fitness and stress tolerance of this organism. Pseudomonassyringae, a member of the gamma subgroup of the Proteobacteria, is awidespread bacterial pathogen of many plant species. The species P.syringae is subdivided into approximately 50 pathovars based onpathogenicity and host range. P. syringae is capable of

Dipeptidyl peptidase-4 (DPP-4) inhibitors are favourable to glucagon-like peptide-1 (GLP-1) agonists

DEFF Research Database (Denmark)

Madsbad, Sten

2012-01-01

Incretin-based therapies, which include the GLP-1 receptor agonists and DPP-4 inhibitors, use the antidiabetic properties of potentiating the GLP-1 receptor signalling via the regulation of insulin and glucagon secretion, inhibition of gastric emptying and suppression of appetite. Most physicians...... will start antidiabetic treatment with metformin, but adding a GLP-1 receptor agonist as the second drug seems to be optimal since more patients will reach an HbA1c below 7% than with a DPP-4 inhibitor or another oral antidiabetic agents and with minimal risk of hypoglycaemia. The GLP-1 receptor agonists...

Reduced plasma concentrations of vitamin B6 and increased ...

African Journals Online (AJOL)

Reduced plasma concentrations of vitamin B6 and increased plasma concentrations of the neurotoxin 3-hydroxykynurenine are associated with nodding syndrome: a case control study in Gulu and Amuru districts, Northern Uganda.

Treatment of type 2 diabetes mellitus with agonists of the GLP-1 receptor or DPP-IV inhibitors

DEFF Research Database (Denmark)

Holst, Jens Juul

2004-01-01

in the treatment of Type 2 diabetes, causing marked improvements in glycaemic profile, insulin sensitivity and beta-cell performance, as well as weight reduction. The hormone is metabolised rapidly by the enzyme dipeptidyl peptidase IV (DPP-IV) and, therefore, cannot be easily used clinically. Instead, resistant...... with exendin have been carried out for > 6 months and have indicated efficacy in patients inadequately treated with oral antidiabetic agents. Orally active DPP-IV inhibitors, suitable for once-daily administration, have demonstrated similar efficacy. Diabetes therapy, based on GLP-1 receptor activation...

Dipeptidyl-peptidase IV (DPP-IV) inhibitor delays tolerance to anxiolytic effect of ethanol and withdrawal-induced anxiety in rats.

Science.gov (United States)

Sharma, Ajaykumar N; Pise, Ashish; Sharma, Jay N; Shukla, Praveen

2015-06-01

Dipeptidyl-peptidase IV (DPP-IV) is an enzyme responsible for the metabolism of endogenous gut-derived hormone, glucagon-like peptide-1 (GLP-1). DPP-IV is known for its role in energy homeostasis and pharmacological blockade of this enzyme is a recently approved clinical strategy for the management of type II diabetes. Accumulating evidences suggest that enzyme DPP-IV can affect spectrum of central nervous system (CNS) functions. However, little is known about the role of this enzyme in ethanol-mediated neurobehavioral complications. The objective of the present study was to examine the impact of DPP-IV inhibitor, sitagliptin on the development of tolerance to anxiolytic effect of ethanol and anxiety associated with ethanol withdrawal in rats. A dose-response study revealed that sitaglitpin (20 mg/kg, p.o.) per se exhibit anxiolytic effect in the elevated plus maze (EPM) test in rats. Tolerance to anxiolytic effect of ethanol (2 g/kg, i.p.; 8 % w/v) was observed from 7(th) day of ethanol-diet (6 % v/v) consumption. In contrast, tolerance to anxiolytic effect of ethanol was delayed in rats that were treated daily with sitagliptin (20 mg/kg, p.o.) as tolerance was observed from 13(th)day since commencement of ethanol-diet consumption. Discontinuation of rats from ethanol-diet after 15-days of ethanol consumption resulted in withdrawal anxiety between 8 h and 12 h post-abstinence. However, rats on 15-day ethanol-diet with concomitant sitagliptin (20 mg/kg, p.o.) treatment exhibited delay in appearance (24 h post-withdrawal) of withdrawal anxiety. In summary, DPP-IV inhibitors may prove as an attractive research strategy against ethanol tolerance and dependence.

Reducing Plasma Perturbations with Segmented Metal Shielding on Electrostatic Probes

International Nuclear Information System (INIS)

Staack, D.; Raitses, Y.; Fisch, N.J.

2002-01-01

Electrostatic probes are widely used to measure spatial plasma parameters in the quasi-neutral plasma created in Hall thrusters and similar E x B electric discharge devices. Significant perturbations of the plasma, induced by such probes, can mask the actual physics involved in operation of these devices. In an attempt to reduce these perturbations in Hall thrusters, the perturbations were examined by varying the component material, penetration distance, and residence time of various probe designs. This study leads us to a conclusion that secondary electron emission from insulator ceramic tubes of the probe can affect local changes of the plasma parameters causing plasma perturbations. A probe design, which consists of a segmented metal shielding of the probe insulator, is suggested to reduce these perturbations. This new probe design can be useful for plasma applications in which the electron temperature is sufficient to produce secondary electron emission by interaction of plasma electrons with dielectric materials

Attenuation of Renovascular Damage in Zucker Diabetic Fatty Rat by NWT-03, an Egg Protein Hydrolysate with ACE- and DPP4-Inhibitory Activity

NARCIS (Netherlands)

Wang, Yumei; Landheer, S.; Gilst, van W.H.; Amerongen, van A.

2012-01-01

Background Dipeptidyl peptidase 4 (DPP4) and angiotensin-converting enzyme (ACE) are important target enzymes in glycemic control and renovascular protection. Here, we studied the effect of NWT-03, an egg protein hydrolysate with DPP4- and ACE-inhibitory activity, on renovascular damage in Zucker

Attenuation of Renovascular Damage in Zucker Diabetic Fatty Rat by NWT-03, an Egg Protein Hydrolysate with ACE- and DPP4-Inhibitory Activity

NARCIS (Netherlands)

Wang, Yumei; Landheer, Sjoerd; van Gilst, Wiek H.; van Amerongen, Aart; Hammes, Hans-Peter; Henning, Robert H.; Deelman, Leo E.; Buikema, Hendrik

2012-01-01

Background: Dipeptidyl peptidase 4 (DPP4) and angiotensin-converting enzyme (ACE) are important target enzymes in glycemic control and renovascular protection. Here, we studied the effect of NWT-03, an egg protein hydrolysate with DPP4- and ACE-inhibitory activity, on renovascular damage in Zucker

Scaffold-hopping from xanthines to tricyclic guanines: A case study of dipeptidyl peptidase 4 (DPP4) inhibitors

Energy Technology Data Exchange (ETDEWEB)

Pissarnitski, Dmitri A.; Zhao, Zhiqiang; Cole, David; Wu, Wen-Lian; Domalski, Martin; Clader, John W.; Scapin, Giovanna; Voigt, Johannes; Soriano, Aileen; Kelly, Theresa; Powles, Mary Ann; Yao, Zuliang; Burnett, Duane A. (Merck)

2016-11-01

Molecular modeling of unbound tricyclic guanine scaffolds indicated that they can serve as effective bioisosteric replacements of xanthines. This notion was further confirmed by a combination of X-ray crystallography and SAR studies, indicating that tricyclic guanine DPP4 inhibitors mimic the binding mode of xanthine inhibitors, exemplified by linagliptin. Realization of the bioisosteric relationship between these scaffolds potentially will lead to a wider application of cyclic guanines as xanthine replacements in drug discovery programs for a variety of biological targets. Newly designed DPP4 inhibitors achieved sub-nanomolar potency range and demonstrated oral activity in vivo in mouse glucose tolerance test.

Mothers After Gestational Diabetes in Australia Diabetes Prevention Program (MAGDA-DPP) post-natal intervention

DEFF Research Database (Denmark)

Shih, Sophy T F; Davis-Lameloise, Nathalie; Janus, Edward D.

2014-01-01

Background: The Mothers After Gestational Diabetes in Australia Diabetes Prevention Program (MAGDA-DPP) is a randomized controlled trial (RCT) that aims to assess the effectiveness of a structured diabetes prevention intervention for women who had gestational diabetes.Methods/Design: The original...

The Effect of Malnutrition on the Pharmacokinetics and Virologic Outcomes of Lopinavir, Efavirenz and Nevirapine in Food Insecure HIV-Infected Children in Tororo, Uganda

Science.gov (United States)

Bartelink, Imke H.; Savic, Rada M.; Dorsey, Grant; Ruel, Theodore; Gingrich, David; Scherpbier, Henriette J.; Capparelli, Edmund; Jullien, Vincent; Young, Sera L.; Achan, Jane; Plenty, Albert; Charlebois, Edwin; Kamya, Moses; Havlir, Diane; Aweeka, Francesca

2014-01-01

Background Malnutrition may impact the pharmacokinetics (PK) of antiretroviral medications and virologic responses in HIV-infected children. We therefore evaluated the PK of nevirapine (NVP), efavirenz (EFV) and lopinavir (LPV) in associations with nutritional status in a cohort of HIV-infected Ugandan children. Methods Sparse dried blood spot (DBS) samples from Ugandan children were used to estimate plasma concentrations. Historical PK data from children from three resource-rich countries (RRC) were utilized to develop the PK models. Results Concentrations in 330 DBS from 163 Ugandan children aged 0.7–7 years were analyzed in reference to plasma PK data (1189 samples) from 204 children from RRC aged 0.5–12 years. Among Ugandan children 48% was malnourished (underweight, thin or stunted). Compared to RRC, Ugandan children exhibited reduced bioavailability of EFV and LPV; 11% (P=0.045) and 18% (P=0.008) respectively. In contrast, NVP bioavailability was 46% higher in Ugandan children (Pmalnutrition on bioavailability. In children receiving NVP, the relation between exposure, malnutrition and outcome turned out to be marginally significant. Further investigations are warranted using more intensive PK measurements and adequate adherence assessements, to further assess causes of virologic failure in Ugandan children. PMID:25742090

New type of discharge-produced plasma source for extreme ultraviolet based on liquid tin jet electrodes

NARCIS (Netherlands)

Koshelev, K.N.; Krivtsun, V.M.; Ivanov, V.; Yakushev, O.; Chekmarev, A.; Koloshnikov, V.; Snegirev, E.; Medvedev, Viacheslav

2012-01-01

A new approach for discharge-produced plasma (DPP) extreme ultraviolet (EUV) sources based on the usage of two liquid metallic alloy jets as discharge electrodes has been proposed and tested. Discharge was ignited using laser ablation of one of the cathode jets. A system with two jet electrodes was

Discovery and characterization of NVP-QAV680, a potent and selective CRTh2 receptor antagonist suitable for clinical testing in allergic diseases.

Science.gov (United States)

Sandham, David A; Arnold, Nicola; Aschauer, Heinrich; Bala, Kamlesh; Barker, Lucy; Brown, Lyndon; Brown, Zarin; Budd, David; Cox, Brian; Docx, Cerys; Dubois, Gerald; Duggan, Nicholas; England, Karen; Everatt, Brian; Furegati, Marcus; Hall, Edward; Kalthoff, Frank; King, Anna; Leblanc, Catherine J; Manini, Jodie; Meingassner, Josef; Profit, Rachael; Schmidt, Alfred; Simmons, Jennifer; Sohal, Bindi; Stringer, Rowan; Thomas, Matthew; Turner, Katharine L; Walker, Christoph; Watson, Simon J; Westwick, John; Willis, Jennifer; Williams, Gareth; Wilson, Caroline

2013-11-01

Optimization of a 7-azaindole-3-acetic acid CRTh2 receptor antagonist chemotype derived from high throughput screening furnished a highly selective compound NVP-QAV680 with low nM functional potency for inhibition of CRTh2 driven human eosinophil and Th2 lymphocyte activation in vitro. The molecule exhibited good oral bioavailability in the rat, combined with efficacy in rodent CRTh2-dependent mechanistic and allergic disease models and was suitable for clinical development. Copyright © 2013 Elsevier Ltd. All rights reserved.

First Russian DPP-4 inhibitor Gosogliptin comparing to Vildagliptin in type 2 diabetes mellitus patients

Directory of Open Access Journals (Sweden)

Karina Oganesovna Galstyan

2015-01-01

The results showed that gosogliptin is an effective hypoglycaemic agent from the group of DPP-4 inhibitors and can be recommended for use in patients with T2DM both as monotherapy and in combination with metformin.

Antioxidative, DPP-IV and ACE inhibiting peptides from fish protein hydrolysed with intestinal proteases

DEFF Research Database (Denmark)

Falkenberg, Susan Skanderup; Stagsted, Jan; Nielsen, Henrik Hauch

amino groups, antioxidative capacity by ABTS (2,2-azinobis(3-ethylbenzothiazoline-6-sulfonicacid)), DPP-IV and ACE inhibiting activity. Degree of hydrolysis (DH) of hydrolysates was approximately 13% and 10% for belly flap and skin respectively. No clear difference was observed in DH between pancreatin...

Maternal deaths following nevirapine-based antiretroviral therapy

Directory of Open Access Journals (Sweden)

E Bera

2012-10-01

Full Text Available We report 2 cases illustrating that it is too simplistic to link nevirapine (NVP toxicity exclusively to individuals with immune preservation. Not enough is known about the mechanism of hepatotoxicity or cutaneous eruption to predict these events. This type of hypersensitivity reaction occurs rarely among HIV-exposed infants taking NVP prophylaxis or antiretroviral therapy (ART-experienced adults with complete plasma viral load suppression. Conversely, HIV-uninfected adults and ART-naive pregnant women appear to be disproportionately affected by the adverse effects of NVP.

Molecular design and ordering effects of alkoxy aromatic donor in a DPP copolymer on OTFTs and OPVs

Energy Technology Data Exchange (ETDEWEB)

Kim, Myeong-Jong [School of Materials Science and Engineering and ERI, Gyeongsang National University, Jinju 660-701 (Korea, Republic of); An, Tae Kyu [POSTECH Organic Electronics Laboratory, Polymer Research Institute, Department of Chemical Engineering, Pohang University of Science and Technology, Pohang 790-784 (Korea, Republic of); Kim, Seul-Ong [School of Materials Science and Engineering and ERI, Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Cha, Hyojung [POSTECH Organic Electronics Laboratory, Polymer Research Institute, Department of Chemical Engineering, Pohang University of Science and Technology, Pohang 790-784 (Korea, Republic of); Kim, Hyoung Nam [Department of Chemistry & Research Institute of Natural Science, Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Xiofeng, Tan [School of Materials Science and Engineering and ERI, Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Park, Chan Eon, E-mail: cep@postech.ac.kr [POSTECH Organic Electronics Laboratory, Polymer Research Institute, Department of Chemical Engineering, Pohang University of Science and Technology, Pohang 790-784 (Korea, Republic of); Kim, Yun-Hi, E-mail: ykim@gnu.ac.kr [Department of Chemistry & Research Institute of Natural Science, Gyeongsang National University, Jinju 660-701 (Korea, Republic of)

2015-03-01

Two p-type polymers, PONDPP and PTADPP were synthesized by Suzuki coupling reaction to investigate the effect of alkoxy aromatic donor units in diketopyrrolopyrrole (DPP)-based copolymers on OTFTs and OPVs. PONDPP containing dialkoxynaphthalene exhibits excellent field-effect performances, with a hole mobility of 0.324 cm{sup 2}/V while PTADPP containing dialkoxyanthracene exhibits mobility of 4.5 × 10{sup −3} cm{sup 2}/V at 200 °C annealing. Bulk heterojunction type polymer solar cells based on these polymers as the electron donor materials, with PC{sub 71}BM as the acceptor, showed maximum power conversion efficiency (PCE) of 0.9% for PONDPP and 1.1% for PTADPP under AM 1.5 illumination. From photophysical and structural studies, we found that naphthalene unit was introduced to the DPP unit to enhance more the molecular ordering compared to anthracene unit. - Highlights: • Two diketopyrrolopyrrole (DPP)-based copolymers, PONDPP and PTADPP were synthesized. • We investigated the effect of alkoxy aromatic donor units on OTFTs and OPVs. • PONDPP and PTADTT exhibit mobilities of 0.324 and 4.5 × 10{sup −3} cm{sup 2}/V. • OPVs showed power conversion efficiency of 0.9% for PONDPP and 1.1% for PTADPP.

Quantitative Evaluation of Compliance with Recommendation for Sulfonylurea Dose Co-Administered with DPP-4 Inhibitors in Japan

Directory of Open Access Journals (Sweden)

Motonobu Sakaguchi

2012-09-01

Full Text Available After the launch of dipeptidyl peptidase-4 (DPP-4, a new oral hypoglycemic drug (OHD, in December 2009, severe hypoglycemia cases were reported in Japan. Although the definite cause was unknown, co-administration with sulfonylureas (SU was suspected as one of the potential risk factors. The Japan Association for Diabetes Education and Care (JADEC released a recommendation in April 2010 to lower the dose of three major SUs (glimepiride, glibenclamide, and gliclazide when adding a DPP-4 inhibitor. To evaluate the effectiveness of this risk minimization action along with labeling changes, dispensing records for 114,263 patients prescribed OHDs between December 2008 and December 2010 were identified in the Nihon-Chouzai pharmacy claims database. The adherence to the recommended dosing of SU co-prescribed with DPP-4 inhibitors increased from 46.3% before to 63.8% after the JADEC recommendation (p < 0.01 by time-series analysis, while no change was found in those for SU monotherapy and SU with other OHD co-prescriptions. The adherence was significantly worse for those receiving a glibenclamide prescription. The JADEC recommendation, along with labeling changes, appeared to have a favorable effect on the risk minimization action in Japan. In these instances, a pharmacy claims database can be a useful tool to evaluate risk minimization actions.

Bisbibenzyls, a new type of antifungal agent, inhibit morphogenesis switch and biofilm formation through upregulation of DPP3 in Candida albicans.

Directory of Open Access Journals (Sweden)

Li Zhang

Full Text Available The yeast-to-hypha transition plays a crucial role in the pathogenesis of C. albicans. Farnesol, a quorum sensing molecule (QSM secreted by the fungal itself, could prevent the formation of hyphae and subsequently lead to the defect of biofilm formation. The DPP3, encoding phosphatase, is a key gene in regulating farnesol synthesis. In this study, we screened 24 bisbibenzyls and 2 bibenzyls that were isolated from bryophytes or chemically synthesized by using CLSI method for antifungal effect. Seven bisbibenzyls were found to have antifungal effects with IC(80 less than 32 µg/ml, and among them, plagiochin F, isoriccardin C and BS-34 were found to inhibit the hyphae and biofilm formation of C. albicans in a dose-dependent manner. To uncover the underlying relationship between morphogenesis switch and QSM formation, we measured the farnesol production by HPLC-MS and quantified Dpp3 expression by detecting the fluorescent intensity of green fluorescent protein tagged strain using Confocal Laser Scanning microscopy and Multifunction Microplate Reader. The DPP3 transcripts were determined by real-time PCR. The data indicated that the bisbibenzyls exerted antifungal effects through stimulating the synthesis of farnesol via upregulation of Dpp3, suggesting a potential antifungal application of bisbibenzyls. In addition, our assay provides a novel, visual and convenient method to measure active compounds against morphogenesis switch.

Effect of the Side Chains and Anode Material on Thermal Stability and Performance of Bulk-Heterojunction Solar Cells Using DPP(TBFu2 Derivatives as Donor Materials

Directory of Open Access Journals (Sweden)

Alexander Kovalenko

2015-01-01

Full Text Available An optimized fabrication of bulk-heterojunction solar cells (BHJ SCs based on previously reported diketopyrrolopyrrole donor, ethyl-hexylated DPP(TBFu2, as well as two new DPP(TBFu2 derivatives with ethyl-hexyl acetate and diethyl acetal solubilizing side-chains and PC60BM as an acceptor is demonstrated. Slow gradual annealing of the solar cell causing the effective donor-acceptor reorganization, and as a result higher power conversion efficiency (PCE, is described. By replacing a hole transporting layer PEDOT:PSS with MoO3 we obtained higher PCE values as well as higher thermal stability of the anode contact interface. DPP(TBFu2 derivative containing ethyl-hexyl acetate solubilizing side-chains possessed the best as-cast self-assembly and high crystallinity. However, the presence of ethyl-hexyl acetate and diethyl acetal electrophilic side-chains stabilizes HOMO energy of isolated DPP(TBFu2 donors with respect to the ethyl-hexylated one, according to cyclic voltammetry.

Implementation of GLP-1 based therapy of type 2 diabetes mellitus using DPP-IV inhibitors

DEFF Research Database (Denmark)

Holst, Jens Juul

2003-01-01

GLP-1 is a peptide hormone from the intestinal mucosa. It is secreted in response to meal ingestion and normally functions in the so-called ileal brake i. e. inhibition of upper gastrointestinal motility and secretion when nutrients are present in the distal small intestine. It also induces satiety...... of the peptide is necessary because of an exceptionally rapid rate of degradation catalyzed the enzyme dipeptidyl peptidase IV. With inhibitors of this enzyme, it is possible to protect the endogenous hormone and thereby elevate both fasting and postprandial levels of the active hormone. This leads to enhanced...... insulin secretion and glucose turnover. But will DPP-IV inhibition enhance all effects of the endogenous peptide? The mode of action of GLP-1 is complex involving also interactions with sensory neurons and the central nervous system, where a DPP-IV mediated degradation does not seem to occur. Therefore...

30 CFR 250.252 - What environmental monitoring information must accompany the DPP or DOCD?

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What environmental monitoring information must accompany the DPP or DOCD? 250.252 Section 250.252 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT... incidental take of marine mammals as may be necessary under the MMPA. (c) Flower Garden Banks National Marine...

ROLE OF DPP-IV INHIBITORS IN TREATMENT OF TYPE II DIABETES

OpenAIRE

Patel Kishan D; Patel Grishma M.

2010-01-01

Emerging as an epidemic of the 21st century type II diabetes has become a major health problem throughout the globe. Known treatments of type II diabetes mellitus have limitations such as weight gain and hypoglycaemias. A new perspective is the use of incretin hormones and incretin enhancers. Incretin mimetics are a new class of pharmacological agents with multiple antihyperglycemic actions that mimic the actions of incretin hormones such as glucagon-like peptide (GLP)-1. DPP-4, a protease th...

Generation of dipeptidyl peptidase IV (DPP-IV) inhibitory peptides during the enzymatic hydrolysis of tropical banded cricket (Gryllodes sigillatus) proteins.

Science.gov (United States)

Nongonierma, Alice B; Lamoureux, Candice; FitzGerald, Richard J

2018-01-24

Tropical banded crickets (Gryllodes sigillatus) were studied for their ability to yield hydrolysates with dipeptidyl peptidase IV (DPP-IV) inhibitory properties. A cricket protein isolate (CPI) was prepared following extraction of the water soluble proteins from G. sigillatus powder (CP). The extraction yield and purity were 20.90 ± 0.35% and 57.0 ± 2.23%, respectively. Endogenous proteinase activities were detected in the CP, which were linked to the significant protein breakdown seen in this sample. Fifteen CPI hydrolysates (H1-H15) were generated with Protamex™ using a design of experiments (DOE) approach combining three parameters, temperature (40, 50 and 60 °C), enzyme to substrate ratio (E : S, 0.50, 1.25 and 2.00% (w/w)) and hydrolysis time (60, 150 and 240 min). The DPP-IV half maximal inhibitory concentrations (IC 50 ) of the CPI hydrolysates ranged from 0.40 ± 0.03/0.40 ± 0.02 (H2/H3) to 1.01 ± 0.07 mg mL -1 (H7). Following simulated gastrointestinal digestion (SGID), the DPP-IV IC 50 of CPI decreased (>3.57 vs. 0.78 ± 0.04 mg mL -1 ) while that of H5 increased (0.47 ± 0.03 vs. 0.71 ± 0.06 mg mL -1 ). This study has demonstrated for the first time that G. sigillatus protein hydrolysates are able to inhibit DPP-IV. The study of these hydrolysates in vivo is needed to evaluate their potential role in glycaemic management.

A technique to reduce plasma armature formation voltage

International Nuclear Information System (INIS)

Jamison, K.A.; Littrell, D.M.

1991-01-01

The initiation of a plasma armature by foil vaporization in a railgun is often accompanied by a large, fast, voltage transient appearing on both the breech and muzzle of the gun. For a railgun driven by an inductor/opening switch power supply, this voltage transient becomes a concern during current commutation from the switch to the railgun. To lessen the requirements on the opening switch, techniques must be found to reduce the armature formation voltage. This paper presents the experimental results from railgun firings at AFATL's Electromagnetic Launcher Basic Research Facility (Site A-15, Eglin Air Force Base, Florida) using different shapes of initiation foils. These foils have been designed to vaporize into a plasma armature with reduced transient voltages. A design criteria was developed to ensure that all portions of the foil vaporize at slightly different times

Managing diabetic patients with moderate or severe renal impairment using DPP-4 inhibitors: focus on vildagliptin

Directory of Open Access Journals (Sweden)

Russo E

2013-04-01

Full Text Available Eleonora Russo, Giuseppe Penno, Stefano Del Prato Department of Clinical and Experimental Medicine, Section of Diabetes and Metabolic Disease, Azienda Ospedaliero Universitaria di Pisa, and University of Pisa, Pisa, Italy Background: Dipeptidyl peptidase-4 (DPP-4 inhibitors are novel classified oral anti-diabetic drugs for the treatment of type 2 diabetes mellitus (T2DM that provide important reduction in glycated hemoglobin, with a low risk for hypoglycemia and no weight gain. In T2DM patients with reduced renal function, adequate glycemic control is essential to delay the progress of kidney dysfunction, but they are at a greater risk of experiencing hypoglycemic events, especially with longer-acting sulfonylureas and meglitinides. Objective: To evaluate vildagliptin as an option to achieve glycemic control in T2DM patients with moderate or severe chronic kidney disease (CKD. Methods: A comprehensive search in the literature was performed using the term "vildagliptin." Original articles and reviews exploring our topic were carefully selected. Results: Vildagliptin provides effective glycemic control in patients with T2DM and CKD. Dose reductions are required for vildagliptin and other DPP-4 inhibitors, except linagliptin, in T2DM patients with moderate-to-severe CKD. Dose of vildagliptin had to be reduced by half (to 50 mg/day both for moderate (estimated glomerular filtration rate [eGFR] ≥30 to ≤50 mL/min and severe CKD (eGFR < 30 mL/min. Available results support a favorable efficacy, safety, and tolerability profile for vildagliptin in T2DM with moderate or severe renal failure. Preliminary data may suggest additional benefits beyond improvement of glycemic control. Conclusion: Vildagliptin can be safely used in T2DM patients with varying degrees of renal impairment. Dose adjustments for renal impairment are required. Potential long-term renal benefit of vildagliptin needs to be further explored. Keywords: type 2 diabetes mellitus, renal

Experience with DPP-4 inhibitors in the management of patients with type 2 diabetes fasting during Ramadan

Directory of Open Access Journals (Sweden)

Schweizer A

2013-12-01

Full Text Available Anja Schweizer,1 Serge Halimi,2,3 Sylvie Dejager4 1Novartis Pharma AG, Basel, Switzerland; 2Department of Diabetology, Endocrinology and Nutrition, University Hospital of Grenoble, France; 3Joseph Fourier University, Grenoble, France; 4Novartis Pharma SAS, Rueil-Malmaison, France Abstract: A large proportion of Muslim patients with type 2 diabetes mellitus (T2DM elect to fast during the holy month of Ramadan. For these patients hypo- and hyperglycemia constitute two major complications associated with the profound changes in food pattern during the Ramadan fast, and efficacious treatment options with a low risk of hypoglycemia are therefore needed to manage their T2DM as effectively and safely as possible. Dipeptidyl peptidase-4 (DPP-4 inhibitors modulate insulin and glucagon secretion in a glucose-dependent manner, and consequently a low propensity of hypoglycemia has consistently been reported across different patient populations with these agents. Promising data with DPP-4 inhibitors have now also started to emerge in patients with T2DM fasting during Ramadan. The objective of this review is to provide a comprehensive overview of the currently available evidence and potential role of DPP-4 inhibitors in the management of patients with T2DM fasting during Ramadan whose diabetes is treated with oral antidiabetic drugs, and to discuss the mechanistic basis for their beneficial effects in this setting. Keywords: dipeptidyl peptidase-4, incretin, type 2 diabetes mellitus, hypoglycemia

32 CFR 728.53 - Department of Labor, Office of Workers' Compensation Programs (OWCP) beneficiaries.

Science.gov (United States)

2010-07-01

... DEPARTMENT FACILITIES Beneficiaries of Other Federal Agencies § 728.53 Department of Labor, Office of Workers... injury) incurred while engaged in: (i) Training. (ii) Flight instructions. (iii) Travel to or from... injury.) This category includes but is not limited to: (i) Civilian student employees in training at Navy...

Fresh Water Cyanobacteria Geitlerinema sp. CCC728 and Arthrospira sp. CCC729 as an Anticancer Drug Resource.

Directory of Open Access Journals (Sweden)

Akanksha Srivastava

Full Text Available An increasing number of cancer patients worldwide, especially in third world countries, have raised concern to explore natural drug resources, such as the less explored fresh water filamentous cyanobacteria. Six strains of cyanobacteria (Phormidium sp. CCC727, Geitlerinema sp. CCC728, Arthrospira sp. CCC729, Phormidium sp. CCC731, Phormidium sp. CCC730, and Leptolyngbya sp. CCC732 were isolated (paddy fields and ponds in the Banaras Hindu University, campus and five strains screened for anticancer potential using human colon adenocarcinoma (HT29 and human kidney adenocarcinoma (A498 cancer cell lines. Geitlerinema sp. CCC728 and Arthrospira sp. CCC729 were the most potent as determined by examination of morphological features and by inhibition of growth by graded concentrations of crude extracts and thin-layer chromatography (TLC eluates. Cell cycle analysis and multiplex assays using cancer biomarkers also confirmed Geitlerinema sp. CCC728 and Arthrospira sp. CCC729 as cancer drug resources. Apoptotic studies in the cells of A498 (cancer and MCF-10A (normal human epithelial exposed to crude extracts and TLC fractions revealed no significant impact on MCF-10A cells emphasizing its importance in the development of anticancer drug. Identification of biomolecules from these extracts are in progress.

Fresh Water Cyanobacteria Geitlerinema sp. CCC728 and Arthrospira sp. CCC729 as an Anticancer Drug Resource.

Science.gov (United States)

Srivastava, Akanksha; Tiwari, Ratnakar; Srivastava, Vikas; Singh, Tej Bali; Asthana, Ravi Kumar

2015-01-01

An increasing number of cancer patients worldwide, especially in third world countries, have raised concern to explore natural drug resources, such as the less explored fresh water filamentous cyanobacteria. Six strains of cyanobacteria (Phormidium sp. CCC727, Geitlerinema sp. CCC728, Arthrospira sp. CCC729, Phormidium sp. CCC731, Phormidium sp. CCC730, and Leptolyngbya sp. CCC732) were isolated (paddy fields and ponds in the Banaras Hindu University, campus) and five strains screened for anticancer potential using human colon adenocarcinoma (HT29) and human kidney adenocarcinoma (A498) cancer cell lines. Geitlerinema sp. CCC728 and Arthrospira sp. CCC729 were the most potent as determined by examination of morphological features and by inhibition of growth by graded concentrations of crude extracts and thin-layer chromatography (TLC) eluates. Cell cycle analysis and multiplex assays using cancer biomarkers also confirmed Geitlerinema sp. CCC728 and Arthrospira sp. CCC729 as cancer drug resources. Apoptotic studies in the cells of A498 (cancer) and MCF-10A (normal human epithelial) exposed to crude extracts and TLC fractions revealed no significant impact on MCF-10A cells emphasizing its importance in the development of anticancer drug. Identification of biomolecules from these extracts are in progress.

How do we reduce plasma transfusion in Rhode Island?

Science.gov (United States)

Nixon, Christian P; Tavares, Maria F; Sweeney, Joseph D

2017-08-01

Plasma transfusions are given to patients with coagulopathy, either prophylactically, before an invasive procedure; or therapeutically, in the presence of active bleeding; and as an exchange fluid in therapeutic plasma exchange for disorders such as thrombotic thrombocytopenic purpura. There is consensus that many prophylactic plasma transfusions are non-efficacious, and the misdiagnosis of thrombotic thrombocytopenic purpura results in unnecessary therapeutic plasma exchange. Beginning in 2001, programs to reduce plasma transfusion in the three major teaching hospitals in Rhode Island were initiated. The programs evolved through the establishment of guidelines, education for key prescribers of plasma, screening of plasma prescriptions, and engagement of individual prescribing physicians for out-of-guidelines prescriptions with modification or cancellation. Establishment of an in-house ADAMTS13 (ADAM metallopeptidase with thrombospondin type 1, motif 13) assay in 2013 was used to prevent therapeutic plasma exchange in patients with non-thrombotic thrombocytopenic purpura microangiopathy. Transfusion service data were gathered at the hospital level regarding blood component use, hospital data for discharges, inpatient mortality, and mean case-mix index, and, at the state level, for units of plasma shipped from the community blood center to in-state hospitals. Between 2006 and 2016, a reduction in plasma use from 11,805 to 2677 units (a 77% decrease) was observed in the three hospitals and was mirrored in the state as a whole. This decline was not associated with any increase in red blood cell transfusion. Inpatient mortality either declined or was unchanged. An active program focused on education and interdiction can achieve a large decrease in plasma transfusions without evidence of patient harm. © 2017 AABB.

Plasma Adenosine Deaminase Enzyme Reduces with Treatment of ...

African Journals Online (AJOL)

olayemitoyin

Plasma Adenosine Deaminase Enzyme Reduces with Treatment of Pulmonary Tuberculosis in Nigerian Patients: Indication for. Diagnosis and Treatment Monitoring. Ige O.a, Edem V.F.b and Arinola O.G.b,*. aDepartment of Medicine, University of Ibadan, Ibadan, Nigeria b Department of Chemical Pathology,. University of ...

Weight neutrality with the DPP-4 inhibitor, vildagliptin: Mechanistic basis and clinical experience

Science.gov (United States)

Foley, James E; Jordan, Jens

2010-01-01

Various factors may confound how diabetes medications affect a patient’s weight. Agents that induce hypoglycemia may promote weight gain through “defensive eating”. Conversely, patients whose hyperglycemia exceeds the renal glucose threshold may overeat to compensate for calories lost in urine and so gain weight when drug therapy ablates glycosuria. Some drugs, such as thiazolidinediones, may promote weight gain via increased lipid storage. Glucagon-like peptide-1 receptor agonists increase satiety, delay gastric emptying, and generally produce weight loss. Dipeptidyl peptidase (DPP)-4 inhibitors are generally weight-neutral, although modest weight loss has been observed with the DPP-4 inhibitor, vildagliptin, in patients with relatively low baseline glycemia. The weight neutrality of vildagliptin likely results in part from its intrinsically low risk for hypoglycemia. Recent studies point to additional potential mechanisms. One study found that drug-naïve patients randomized to vildagliptin exhibited significantly lower chylomicron lipid and apolipoprotein levels than placebo patients, suggesting that vildagliptin may inhibit intestinal fat extraction. Another trial found that patients randomized to vildagliptin versus placebo experienced paradoxical postprandial increases in markers of fatty acid mobilization and oxidation, in conjunction with increased sympathetic stimulation. Elaboration of these and other pathways could further clarify the origins of the favorable weight profile of vildagriptin. PMID:20730070

The tunable plasma synthesis of Pt-reduced graphene oxide nanocomposites

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Yulong Ma

2017-06-01

Full Text Available Herein, we have developed Pt-plasma reduced graphene oxide (Pt/P-rGO catalysts displaying high overpotentials for methanol oxidation reaction (MOR through facile and tunable plasma treatments. We provide insight into the improved performance of these catalysts by combining electrochemical measurements with microscopic and spectroscopic characterization techniques. The analysis results showed that the Pt nanoparticles (NPs were successfully deposited on P-rGO. The deposition and uniformity of Pt NPs were influenced by tuning the discharge power of the plasma. The catalytic performance towards the methanol oxidation reaction is investigated. The Pt/P-rGO NPs composites under 100 W show the best electrocatalytic activity. These results were vital to the further application of graphene-based metal nanocomposites synthesized by plasma technology.

A reduced model for ion temperature gradient turbulent transport in helical plasmas

International Nuclear Information System (INIS)

Nunami, M.; Watanabe, T.-H.; Sugama, H.

2013-07-01

A novel reduced model for ion temperature gradient (ITG) turbulent transport in helical plasmas is presented. The model enables one to predict nonlinear gyrokinetic simulation results from linear gyrokinetic analyses. It is shown from nonlinear gyrokinetic simulations of the ITG turbulence in helical plasmas that the transport coefficient can be expressed as a function of the turbulent fluctuation level and the averaged zonal flow amplitude. Then, the reduced model for the turbulent ion heat diffusivity is derived by representing the nonlinear turbulent fluctuations and zonal flow amplitude in terms of the linear growth rate of the ITG instability and the linear response of the zonal flow potentials. It is confirmed that the reduced transport model results are in good agreement with those from nonlinear gyrokinetic simulations for high ion temperature plasmas in the Large Helical Device. (author)

Pharmacological Evaluation of Total Alkaloids from Nux Vomica: Effect of Reducing Strychnine Contents

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Jun Chen

2014-04-01

Full Text Available The aim of the study was to investigate the possibility of improving the therapeutic efficacy of the total alkaloid fraction (TAF extracted from processed nux vomica by reducing the strychnine contents. Most strychnine was removed from TAF to obtain the modified total alkaloid fraction (MTAF. The toxicity and pharmacokinetics of TAF and MTAF were further investigated and compared besides their antitumor, analgesic and anti-inflammatory activities. The results showed that the ratios of brucine to strychnine were 1:2.05 and 2.2:1 for TAF and MTAF, respectively, and the toxicity of TAF was about 3.17-fold higher than that of MTAF. Compared to brucine alone, the elimination of brucine was found to be inhibited by other alkaloids in TAF or MTAF except strychnine. Significantly increased pharmacological activities when administered by the oral route were obtained with MTAF in comparison to TAF and nux vomica powder (NVP. In summary, MTAF might replace NVP and TAF in the clinical application of Chinese medicine to obtain much higher efficacy.

Plasma gelsolin is reduced in trauma patients

DEFF Research Database (Denmark)

Dahl, B; Schiødt, F V; Ott, P

1999-01-01

in the circulation can lead to a condition resembling multiple organ dysfunction syndrome (MODS), and we have previously demonstrated that the level of Gc-globulin is decreased after severe trauma. The purpose of the present study was to determine whether the plasma levels of gelsolin were altered in the early phase...... after trauma. Twenty-three consecutive trauma patients were studied. Plasma samples were assayed for gelsolin by immunonephelometry with polyclonal rabbit antihuman gelsolin prepared in our own laboratory. The median time from injury until the time the first blood sample was taken was 52 min (range 20......-110) and the median Injury Severity Score (ISS) was 20 (range 4-50). The gelsolin level on admission was reduced significantly in the trauma patients compared with normal controls. The median level was 51 mg/L (7-967) vs. 207 mg/L (151-621), P

Laser Plasma Instability (LPI) Driven Light Scattering Measurements with 44 beam-lines of Nike KrF Laser^*

Science.gov (United States)

Oh, J.; Weaver, J. L.; Kehne, D. M.; Phillips, L. S.; Obenschain, S. P.; Serlin, V.; McLean, E. A.; Lehmberg, R. H.; Manka, C. K.

2009-11-01

With short wavelength (248 nm), large bandwidth (˜1 THz), and ISI beam smoothing, Nike KrF laser provides unique opportunities of LPI research for direct-drive inertial confinement fusion. Previous experiments at intensities (10^15˜10^16 W/cm^2) exceeded two-plasmon decay (TPD) instability threshold using 12 beam-lines of Nike laser.^a,b For further experiments to study LPI excitation in bigger plasma volumes, 44 Nike main beams have been used to produce plasmas with total laser energies up to 1 kJ of ˜350 psec FWHM pulses. This talk will present results of the recent LPI experiment focusing on light emission data in spectral ranges relevant to the Raman (SRS) and TPD instabilities. The primary diagnostics were time-resolved spectrometers with an absolute-intensity-calibrated photodiode array in (0.4˜0.8)φ0 and a streak camera near 0.5φ0. Blackbody temperature and expansion speed measurements of the plasmas were also made. The experiment was conducted at laser intensities of (1˜4)x10^15 W/cm^2 on solid planar CH targets. ^a J. L. Weaver, et al, NO4.14, APS DPP (2008) ^b J. Oh, et al, NO4.15, APS DPP (2008) * Work supported by DoE/NNSA and performed at Naval Research Laboratory.

Does the treatment of type 2 diabetes mellitus with the DPP-4 inhibitor vildagliptin reduce HbA1c to a greater extent in Japanese patients than in Caucasian patients?

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Foley JE

2016-01-01

Full Text Available James E Foley,1 Vaishali Bhosekar,2 Ryuzo Kawamori3 1Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 2Novartis Healthcare Pvt Ltd, Hyderabad, Telangana, India; 3Sportology Center, Juntendo University Graduate School of Medicine, Juntendo University, Tokyo, Japan Background: Previous work suggests that Japanese patients with type 2 diabetes mellitus (T2DM may respond more favorably to a DPP-4 (dipeptidyl peptidase-4 inhibitor than Caucasians. We aimed to compare the efficacy of the DPP-4 inhibitor vildagliptin (50 mg twice daily [bid] between Japanese and Caucasian populations. Methods: This analysis pooled data from 19 studies of drug-naïve patients with T2DM who were treated for 12 weeks with vildagliptin 50 mg bid as monotherapy. The pool comprised Japanese patients (n=338 who had been treated in Japan and Caucasian patients (n=1,275 who were treated elsewhere. Change from baseline (Δ in glycated hemoglobin (HbA1c at 12 weeks (in millimoles per mole versus baseline HbA1c (both in percentage National Glycohemoglobin Standardization Program units [NGSP%] and millimoles per mole for each population was reported. Universal HbA1c in millimoles per mole was calculated from either the Japanese Diabetes Society or the NGSP% HbA1c standards. Results: At baseline, mean values for Japanese and Caucasian patients, respectively, were as follows: age, 59 years and 56 years; % male, 69% and 57%. The average HbA1c was reduced from 7.90% to 6.96% (Japanese Diabetes Society and from 8.57% to 7.50% (United States National Glycohemoglobin Standardization Program, while HbA1c was reduced from 63 mmol/mol to 53 mmol/mol and from 70 mmol/mol to 58 mmol/mol in Japanese and Caucasians, respectively. ΔHbA1c increased with increasing baseline in both populations. The slopes were the same (0.41, r2=0.36; and 0.41, r2=0.15, and the intercepts were 15.4 mmol/mol and 17.2 mmol/mol, respectively. In Japanese patients, mean ΔHbA1c was greater by 1.7 mmol

Inhibition of DPP-4 with vildagliptin improved insulin secretion in response to oral as well as "isoglycemic" intravenous glucose without numerically changing the incretin effect in patients with type 2 diabetes

DEFF Research Database (Denmark)

Vardarli, Irfan; Nauck, Michael A; Köthe, Lars D

2011-01-01

Dipeptidyl peptidase-4 (DPP-4) inhibitors block the degradation of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. The aim of the present study was to quantitatively assess the incretin effect after treatment with the DPP-4 inhibitor vildagliptin (V) or placebo (P...

Use of DPP-4 inhibitors in type 2 diabetes: focus on sitagliptin

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Bo Ahrén

2010-03-01

Full Text Available Bo AhrénDepartment of Clinical Sciences, Lund University, Lund, SwedenAbstract: Inhibition of dipeptidyl peptidase-4 (DPP-4 prevents the inactivation of glucagonlike peptide-1 (GLP-1. This increases circulating levels of active GLP-1, stimulates insulin secretion and inhibits glucagon secretion, which results in lowering of glucose levels and improvement of the glycemic control in patients with type 2 diabetes. This review summarizes experiences with DPP-4 inhibition in the treatment of type 2 diabetes, with a focus on sitagliptin. Sitagliptin has in several clinical studies been shown to improve metabolic control in type 2 diabetes, both when used as monotherapy and when used in combination with metformin, sulfonylurea, thiazolidinediones or insulin. The reduction in HbA1c is ≈0.6% to 1.0% from baseline levels of 7.5% to 8.7% over 6 to 12 months therapy. Sitagliptin has a favorable safety profile, is highly tolerable, and there is a minimal risk of hypoglycemia. Furthermore, sitagliptin is body weight neutral or induces a slight body weight reduction. Sitagliptin may be used in the early stages of type 2 diabetes in combination with metformin or other treatments in subjects with inadequate glycemic control on these treatments alone. Sitagliptin may also be used in monotherapy and, finally, sitagliptin may be used in combination with insulin in more advanced stages of the disease.Keywords: glucagon-like peptide-1, dipeptidyl peptidase-4, type 2 diabetes, sitagliptin, treatment

A study of factors affecting properties of AM/AMPS/NVP terpolymeric microspheres prepared by inverse suspension polymerization

Science.gov (United States)

Jiang, J. F.; Zhao, Q.; Lin, M. Q.; Wang, Y. F.; Dang, S. M.; Sun, F. F.

2015-12-01

Terpolymeric microspheres were synthesized by the inverse suspension polymerization of functional monomers including AMPS, NVP, and AM. The morphology and size of the obtained microspheres were measured by scanning electron microscopy (SEM) and optical microscopy. Furthermore, the swelling performances of the obtained microspheres were measured with alaser particle analyzer (LPA), and the thermal stability of the microspheres obtained was measured by differential thermal analysis (DSC-TG) and high temperature experiments involving microsphere/water dispersion. The results revealed that the extreme value of the microsphere size distribution decreased from 280 μm to 20 μm as the stirring rate increased from 175 rpm to 500 rpm. At temperatures below 25°C, the maximum achieved swelling ratio of the microspheres was 21, and the thermal stability of the terpolymer microspheres was significantly higher than that of the dipolymer microspheres. The terpolymer/water dispersions were kept at 120°C for 19d before any damage was observed.

The effects of aerobic exercises and 25(OH D supplementation on GLP1 and DPP4 level in Type II diabetic patients

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Naser Rahimi

2017-01-01

Full Text Available Background: The purpose of this study was to investigate the effects of an 8-week aerobic exercise and supplementation of 25(OHD3 on GLP1 and DDP4 levels in men with type II diabetes. Methods: In this semiexperimental research, among 40–60-year-old men with type II diabetes who were referred to the diabetic center of Isabn-E Maryam hospital in Isfahan; of whom, 48 patients were voluntarily accepted and then were randomly divided into 4 groups: aerobic exercise group, aerobic exercise with 25(OH D supplement group, 25(OH D supplement group, and the control group. An aerobic exercise program was conducted for 8 weeks (3 sessions/week, each session 60 to75 min with 60–80% HRmax. The supplement user group received 50,000 units of oral Vitamin D once weekly for 8 weeks. The GLP1, DPP4, and 25(OH D levels were measured before and after the intervention. At last, the data were statistically analyzed using the ANCOVA and post hoc test of least significant difference. Results: The results of ANCOVA showed a significant difference between the GLP1 and DPP4 levels in aerobic exercise with control group while these changes were not statistically significant between the 25(OH D supplement group with control group (P < 0.05. Conclusions: Aerobic exercises have resulted an increase in GLP1 level and a decrease in DPP4 level. However, consumption of Vitamin D supplement alone did not cause any changes in GLP1and DPP4 levels but led to an increase in 25-hydroxy Vitamin D level.

30 CFR 250.261 - What environmental impact analysis (EIA) information must accompany the DPP or DOCD?

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What environmental impact analysis (EIA) information must accompany the DPP or DOCD? 250.261 Section 250.261 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Plans and Information Contents of...

The efficacy of therapy with DPP-4 inhibitors combined with insulin in patients with type 2 diabetes mellitus

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Alexander Sergeevich Ametov

2011-12-01

Full Text Available Recently, researchers started to pay increasingly more attention to the role of gastrointestinal hormones in regulation of insulin secretion, i.e. glucosehomeostasis. To-day, there are two approaches to the treatment of DM based on the use of GLP-1 effects. One takes advantage of DPP-4 inhibitorsthe other is combination of these agents with various drugs necessitated by heterogeneity of pathophysiological factors responsible for the developmentof DM2. The latter approach ensures multiple therapeutic effects on DM2 and its complications. Many on-going studies are focused on the use ofcombination of DPP-4 inhibitors and insulin. Vildagliptin (Galvus, Novartis Pharma, Switzerland is presently the sole DPP-4 inhibitor approvedfor application with insulin in Russia.Aim. To estimate the efficacy and safety of DPP-4 inhibitor combined with long-acting insulin in the treatment of DM2. Materials and methods. The study group included 18 patients (2 men and 16 women with DM2 treated with long-acting insulin (glargine, humulinNPH for at least 3 months at a mean daily dose of 31.96?4.95 U. The age of the patients averaged 59.9?2.84 years (46-75, DM2 duration8.9?1.18 years (2-15. Parameters of comprehensive glycemic control (FG, PPG, HbA1c, LMWH - low-molecular weight heparins CGM-continuousglucose monitoring were measured using a CGMS system in the beginning and end of the study. Functional activity of pancreatic betbeta-cells and insulinresistance (HOMA-IR, lipid metabolism, and anthropometric characteristics were estimated. Results. Combined therapy resulted in positive dynamics of carbohydrate metabolism within 12 weeks after onset. The functional activity of pancreaticbetbeta-cells significantly (by 157.96 U improved by the end of the study. Changes of HOMA-IR were insignificant. CGM showed that prescription ofvildagliptin to the patients who failed to reach compensation of DM2 with long-acting insulin alone significantly improved glycemic control

30 CFR 250.260 - What Coastal Zone Management Act (CZMA) information must accompany the DPP or DOCD?

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What Coastal Zone Management Act (CZMA) information must accompany the DPP or DOCD? 250.260 Section 250.260 Mineral Resources MINERALS MANAGEMENT... Operations Coordination Documents (docd) § 250.260 What Coastal Zone Management Act (CZMA) information must...

Defining the role of GLP-1 in the enteroinsulinar axis in type 2 diabetes using DPP-4 inhibition and GLP-1 receptor blockade

DEFF Research Database (Denmark)

Aulinger, Benedikt A; Bedorf, Anne; Kutscherauer, Gabriele

2014-01-01

Understanding the incretin pathway has led to significant advancements in the treatment of type 2 diabetes (T2D). Still, the exact mechanisms are not fully understood. In a randomized, placebo-controlled, four-period, crossover study in 24 patients with T2D, dipeptidyl peptidase-4 (DPP-4) inhibit......Understanding the incretin pathway has led to significant advancements in the treatment of type 2 diabetes (T2D). Still, the exact mechanisms are not fully understood. In a randomized, placebo-controlled, four-period, crossover study in 24 patients with T2D, dipeptidyl peptidase-4 (DPP-4...

UPPER LIMITS ON PULSED RADIO EMISSION FROM THE 6.85 s X-RAY PULSAR XTE J0103-728 IN THE SMALL MAGELLANIC CLOUD

International Nuclear Information System (INIS)

Crawford, Fronefield; Devour, Brian M.; Takacs, Brian P.; Lorimer, Duncan R.; Kondratiev, Vladislav I.

2009-01-01

X-ray pulsations with a 6.85 s period were recently detected in the Small Magellanic Cloud (SMC) and were subsequently identified as originating from the Be/X-ray binary system XTE J0103-728. The recent localization of the source of the X-ray emission has made a targeted search for radio pulsations from this source possible. The detection of pulsed radio emission from XTE J0103-728 would make it only the second system after PSR B1259-63 that is both a Be/X-ray binary and a radio pulsar. We observed XTE J0103-728 in 2008 February with the Parkes 64 m radio telescope soon after the identification of the source of X-ray pulsations was reported in order to search for corresponding radio pulsations. We used a continuous 6.4 hr observation with a 256 MHz bandwidth centered at 1390 MHz using the center beam of the Parkes multibeam receiver. In the subsequent data analysis, which included a folding search, a Fourier search, a fast-folding algorithm search, and a single pulse search, no pulsed signals were found for trial dispersion measures (DMs) between 0 and 800 pc cm -3 . This DM range easily encompasses the expected values for sources in the SMC. We place an upper limit of ∼45 mJy kpc 2 on the luminosity of periodic radio emission from XTE J0103-728 at the epoch of our observation, and we compare this limit to a range of luminosities measured for PSR B1259-63, the only Be/X-ray binary currently known to emit radio pulses. We also compare our limit to the radio luminosities of neutron stars having similarly long spin periods to XTE J0103-728. Since the radio pulses from PSR B1259-63 are eclipsed and undetectable during the portion of the orbit near periastron, repeated additional radio search observations of XTE J0103-728 may be valuable if it is undergoing similar eclipsing and if such observations are able to sample the orbital phase of this system well.

18-month effectiveness of short-course antiretroviral regimens combined with alternatives to breastfeeding to prevent HIV mother-to-child transmission.

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Valériane Leroy

Full Text Available OBJECTIVE: We assessed the 18-month effectiveness of short-course (sc antiretroviral peripartum regimens combined with alternatives to prolonged breastfeeding to prevent mother-to-child transmission (MTCT of HIV-1 in Abidjan, Côte d'Ivoire. METHODOLOGY: HIV-1 infected pregnant women received from >/=32-36 weeks of gestation scZidovudine (ZDV+/-Lamivudine (3TC+single-dose Nevirapine (sdNVP at delivery within the ANRS 1201/1202 DITRAME-Plus cohort (2001-2003. Neonates received a sdNVP+7-day ZDV prophylaxis. Two infant-feeding interventions were systematically offered free of charge: formula-feeding or exclusive shortened breastfeeding with early cessation from four months. The reference group was the ANRS 049a DITRAME cohort (1994-2000 exposed to scZDV from 36 weeks, then to prolonged breastfeeding. Pediatric HIV infection was defined by a positive plasma HIV-1 RNA at any age, or if aged >/=18 months, a positive HIV-1 serology. Turnbull estimates of cumulative transmission risks (CTR and effectiveness (HIV-free survival were compared by exposure group using a Cox model. FINDINGS: Among 926 live-born children enrolled, 107 (11.6% were HIV-infected at 18 months. CTRs were 22.3% (95% confidence interval[CI]:16-30% in the 238 ZDV long-term breastfed reference group, 15.9% (CI:10-27% in the 169 ZDV+sdNVP shortened breastfed group; 9.4% (CI:6-14% in the 195 ZDV+sdNVP formula-fed group; 6.8% (CI:4-11% in the 198 ZDV+3TC+sdNVP shortened breastfed group, and 5.6% (CI:2-10% in the 126 ZDV+3TC+sdNVP formula-fed group. Each combination had a significantly higher effectiveness than the ZDV long-term breastfed group except for ZDV+sdNVP shortened breastfed children, ranging from 51% (CI:20-70% for ZDV+sdNVP formula fed children to 63% (CI:40-80% for ZDV+3TC+NVPsd shortened breastfed children, after adjustment for maternal eligibility for antiretroviral therapy (ART, home delivery and low birth-weight. Substantial MTCT risk reductions are reachable in Africa

Controlling the Morphology of BDTT-DPP-Based Small Molecules via End-Group Functionalization for Highly Efficient Single and Tandem Organic Photovoltaic Cells.

Science.gov (United States)

Kim, Ji-Hoon; Park, Jong Baek; Yang, Hoichang; Jung, In Hwan; Yoon, Sung Cheol; Kim, Dongwook; Hwang, Do-Hoon

2015-11-04

A series of narrow-band gap, π-conjugated small molecules based on diketopyrrolopyrrole (DPP) electron acceptor units coupled with alkylthienyl-substituted-benzodithiophene (BDTT) electron donors were designed and synthesized for use as donor materials in solution-processed organic photovoltaic cells. In particular, by end-group functionalization of the small molecules with fluorine derivatives, the nanoscale morphologies of the photoactive layers of the photovoltaic cells were successfully controlled. The influences of different fluorine-based end-groups on the optoelectronic and morphological properties, carrier mobilities, and the photovoltaic performances of these materials were investigated. A high power conversion efficiency (PCE) of 6.00% under simulated solar light (AM 1.5G) illumination has been achieved for organic photovoltaic cells based on a small-molecule bulk heterojunction system consisting of a trifluoromethylbenzene (CF3) end-group-containing oligomer (BDTT-(DPP)2-CF3) as the donor and [6,6]-phenyl-C71-butyric acid methyl ester (PC71BM) as the acceptor. As a result, the introduction of CF3 end-groups has been found to enhance both the short circuit current density (JSC) and fill factor (FF). A tandem photovoltaic device comprising an inverted BDTT-(DPP)2-CF3:PC71BM cell and a poly(3-hexylthiophene) (P3HT):indene-C60-bisadduct (IC60BA)-based cell as the top and bottom cell components, respectively, showed a maximum PCE of 8.30%. These results provide valuable guidelines for the rational design of conjugated small molecules for applications in high-performance organic photovoltaic cells. Furthermore, to the best of our knowledge, this is the first report on the design of fluorine-functionalized BDTT-DPP-based small molecules, which have been shown to be a viable candidate for use in inverted tandem cells.

Identification of Potential Plasma Biomarkers for Nonalcoholic Fatty Liver Disease by Integrating Transcriptomics and Proteomics in Laying Hens.

Science.gov (United States)

Tsai, Meng-Tsz; Chen, Yu-Jen; Chen, Ching-Yi; Tsai, Mong-Hsun; Han, Chia-Li; Chen, Yu-Ju; Mersmann, Harry J; Ding, Shih-Torng

2017-03-01

Background: Prevalent worldwide obesity is associated with increased incidence of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. The identification of noninvasive biomarkers for NAFLD is of recent interest. Because primary de novo lipogenesis occurs in chicken liver as in human liver, adult chickens with age-associated steatosis resembling human NAFLD is an appealing animal model. Objective: The objective of this study was to screen potential biomarkers in the chicken model for NAFLD by transcriptomic and proteomic analysis. Methods: Hy-Line W-36 laying hens were fed standard feed from 25 to 45 wk of age to induce fatty liver. They were killed every 4 wk, and liver and plasma were collected at each time point to assess fatty liver development and for transcriptomic and proteomic analysis. Next, selected biomarkers were confirmed in additional experiments by providing supplements of the hepatoprotective nutrients betaine [300, 600, or 900 parts per million (ppm) in vivo; 2 mM in vitro] or docosahexaenoic acid (DHA; 1% in vivo; 100 μM in vitro) to 30-wk-old Hy-Line W-36 laying hens for 4 mo and to Hy-Line W-36 chicken primary hepatocytes with oleic acid-induced steatosis. Liver or hepatocyte lipid contents and the expression of biomarkers were then examined. Results: Plasma acetoacetyl-CoA synthetase (AACS), dipeptidyl-peptidase 4 (DPP4), glutamine synthetase (GLUL), and glutathione S -transferase (GST) concentrations are well-established biomarkers for NAFLD. Selected biomarkers had significant positive associations with hepatic lipid deposition ( P steatosis accompanied by the reduced expression of selected biomarkers in vivo and in vitro ( P < 0.05). Conclusion: This study used adult laying hens to identify biomarkers for NAFLD and indicated that AACS, DPP4, GLUL, and GST could be considered to be potential diagnostic indicators for NAFLD in the future. © 2017 American Society for Nutrition.

Association between DPP6 polymorphism and the risk of progressive multiple sclerosis in Northern and Southern Europeans

DEFF Research Database (Denmark)

Brambilla, Paola; Esposito, Federica; Lindstrom, Eva

2012-01-01

In this study, we investigated the role of the dipeptidyl-peptidase-6 (DPP6) gene in the etiopathogenesis of progressive forms of multiple sclerosis (PrMS). This gene emerged as a candidate gene in a genome-wide association study (GWAS) performed in an Italian sample of PrMS and controls in which...

Tailoring properties of reduced graphene oxide by oxygen plasma treatment

Science.gov (United States)

Kondratowicz, Izabela; Nadolska, Małgorzata; Şahin, Samet; Łapiński, Marcin; Prześniak-Welenc, Marta; Sawczak, Mirosław; Yu, Eileen H.; Sadowski, Wojciech; Żelechowska, Kamila

2018-05-01

We report an easily controllable, eco-friendly method for tailoring the properties of reduced graphene oxide (rGO) by means of oxygen plasma. The effect of oxygen plasma treatment time (1, 5 and 10 min) on the surface properties of rGO was evaluated. Physicochemical characterization using microscopic, spectroscopic and thermal techniques was performed. The results revealed that different oxygen-containing groups (e.g. carboxyl, hydroxyl) were introduced on the rGO surface enhancing its wettability. Furthermore, upon longer treatment time, other functionalities were created (e.g. quinones, lactones). Moreover, external surface of rGO was partially etched resulting in an increase of the material surface area and porosity. Finally, the oxygen plasma-treated rGO electrodes with bilirubin oxidase were tested for oxygen reduction reaction. The study showed that rGO treated for 10 min exhibited twofold higher current density than untreated rGO. The oxygen plasma treatment may improve the enzyme adsorption on rGO electrodes by introduction of oxygen moieties and increasing the porosity.

Inhibition of histone deacetylase for the treatment of biliary tract cancer: A new effective pharmacological approach

Science.gov (United States)

Bluethner, Thilo; Niederhagen, Manuel; Caca, Karel; Serr, Frederik; Witzigmann, Helmut; Moebius, Christian; Mossner, Joachim; Wiedmann, Marcus

2007-01-01

AIM: To investigate in vitro and in vivo therapeutic effects of histone deacetylase inhibitors NVP-LAQ824 and NVP-LBH589 on biliary tract cancer. METHODS: Cell growth inhibition by NVP-LAQ824 and NVP-LBH589 was studied in vitro in 7 human biliary tract cancer cell lines by MTT assay. In addition, the anti-tumoral effect of NVP-LBH589 was studied in a chimeric mouse model. Anti-tumoral drug mechanism was assessed by immunoblotting for acH4 and p21WAF-1/CIP-1, PARP assay, cell cycle analysis, TUNEL assay, and immunhistochemistry for MIB-1. RESULTS: In vitro treatment with both compounds significantly suppressed the growth of all cancer cell lines [mean IC50 (3 d) 0.11 and 0.05 μmol/L, respectively], and was associated with hyperacetylation of nucleosomal histone H4, increased expression of p21WAF-1/CIP-1, induction of apoptosis (PARP cleavage), and cell cycle arrest at G2/M checkpoint. After 28 d, NVP-LBH589 significantly reduced tumor mass by 66% (bile duct cancer) and 87% (gallbladder cancer) in vivo in comparison to placebo, and potentiated the efficacy of gemcitabine. Further analysis of the tumor specimens revealed increased apoptosis by TUNEL assay and reduced cell proliferation (MIB-1). CONCLUSION: Our findings suggest that NVP-LBH589 and NVP-LAQ824 are active against human biliary tract cancer in vitro. In addition, NVP-LBH589 demonstrated significant in vivo activity and potentiated the efficacy of gemcitabine. Therefore, further clinical evaluation of this new drug for the treatment of biliary tract cancer is recommended. PMID:17729398

Important species differences regarding lymph contribution to gut hormone responses

DEFF Research Database (Denmark)

Hansen, Marie; Hjøllund, Karina R; Hartmann, Bolette

2015-01-01

pigs of the YDL-strain were catheterized in the portal vein, carotid artery and cisterna chyli (lymph). Neuromedin C (NC) was infused through an ear vein catheter, before and after injection of a selective DPP-4 inhibitor (vildagliptin). Total and intact GLP-1 levels were measured throughout the 150min....../presence of vildagliptin. In contrast, total and intact GLP-1 levels increased significantly in the portal vein and carotid artery. DPP-4 activity was lower in lymph than plasma, and was reduced further by vildagliptin. CONCLUSION: Our observations indicate that the lymphatic system does not transport high levels...

The GABAA Antagonist DPP-4-PIOL Selectively Antagonises Tonic over Phasic GABAergic Currents in Dentate Gyrus Granule Cells

DEFF Research Database (Denmark)

Boddum, Kim; Frølund, Bente; Kristiansen, Uffe

2014-01-01

that phasic and tonic GABAA receptor currents can be selectively inhibited by the antagonists SR 95531 and the 4-PIOL derivative, 4-(3,3-diphenylpropyl)-5-(4-piperidyl)-3-isoxazolol hydrobromide (DPP-4-PIOL), respectively. In dentate gyrus granule cells, SR 95531 was found approximately 4 times as potent...

Moringa Oleifera leaf extract increases plasma antioxidant status associated with reduced plasma malondialdehyde concentration without hypoglycemia in fasting healthy volunteers.

Science.gov (United States)

Ngamukote, Sathaporn; Khannongpho, Teerawat; Siriwatanapaiboon, Marent; Sirikwanpong, Sukrit; Dahlan, Winai; Adisakwattana, Sirichai

2016-12-29

To investigate the effect of Moringa Oleifera leaf extract (MOLE) on plasma glucose concentration and antioxidant status in healthy volunteers. A randomized crossover design was used in this study. Healthy volunteers were randomly assigned to receive either 200 mL of warm water (10 cases) or 200 mL of MOLE (500 mg dried extract, 10 cases). Blood samples were drawn at 0, 30, 60, 90, and 120 min for measuring fasting plasma glucose (FPG), ferric reducing ability of plasma (FRAP), Trolox equivalent antioxidant capacity (TEAC) and malondialdehyde (MDA). FPG concentration was not signifificantly different between warm water and MOLE. The consumption of MOLE acutely improved both FRAP and TEAC, with increases after 30 min of 30 μmol/L FeSO 4 equivalents and 0.18 μmol/L Trolox equivalents, respectively. The change in MDA level from baseline was signifificantly lowered after the ingestion of MOLE at 30, 60, and 90 min. In addition, FRAP level was negatively correlated with plasma MDA level after an intake of MOLE. MOLE increased plasma antioxidant capacity without hypoglycemia in human. The consumption of MOLE may reduce the risk factors associated with chronic degenerative diseases.

On the influence of plasma DBD actuator on the flow in a rectangular channel

Czech Academy of Sciences Publication Activity Database

Procházka, Pavel P.; Uruba, Václav

2014-01-01

Roč. 14, č. 1 (2014), s. 727-728 ISSN 1617-7061. [Annual Meeting of the International Association of Applied Mathematics and Mechanics /85./. Erlangen, 10.03.2014-14.03.2014] R&D Projects: GA ČR(CZ) GP14-25354P Institutional support: RVO:61388998 Keywords : plasma DBD * boundary layer * channel flow Subject RIV: BK - Fluid Dynamics http://onlinelibrary.wiley.com/doi/10.1002/pamm.201410346/abstract

Low rate of mother-to-child transmission of HIV-1 after nevirapine intervention in a pilot public health program in Yaoundé, Cameroon.

Science.gov (United States)

Ayouba, Ahidjo; Tene, Gilbert; Cunin, Patrick; Foupouapouognigni, Yacouba; Menu, Elisabeth; Kfutwah, Anfumbom; Thonnon, Jocelyn; Scarlatti, Gabriella; Monny-Lobé, Marcel; Eteki, Nicole; Kouanfack, Charles; Tardy, Michèle; Leke, Robert; Nkam, Maurice; Nlend, Anne E; Barré-Sinoussi, Françoise; Martin, Paul M V; Nerrienet, Eric

2003-11-01

To determine the percentage of infected children for whom nevirapine (NVP) was used to prevent peripartum mother-to-child transmission (MTCT) of HIV in Yaoundé, Cameroon. The study was a prospective Public Health Pilot Program covering a 3-year period (January 2000-December 2002). Counseled and consenting HIV-1-positive pregnant women were given a single dose of NVP at the onset of labor. Babies were given 2 mg/kg NVP syrup within the first 72 hours of life. NVP-treated children were regularly followed up and examined for HIV-1 infection at 6-8 weeks and 5-6 months through plasma viral load (VL) quantification with the bDNA system. One hundred twenty-three children were diagnosed with perinatal HIV-1 infection at 6-8 weeks and 5-6 months. Thirteen children (10.6% [13/123]; 95% confidence interval, 5.1-16) were infected and presented with high VLs, in general >500,000 copies/mL. Two children had intermediate VLs (between 50 and 3500 copies/mL) at both time points. One hundred seven children (87%) were considered not infected at 6-8 weeks of age. Our results indicate that the HIV-1 MTCT rate 6-8 weeks after NVP administration was not >13% (16/123), thus demonstrating the effectiveness of NVP for lowering the risk of HIV-1 MTCT in real-life settings.

Linagliptin, a xanthine-based dipeptidyl peptidase-4 inhibitor with an unusual profile for the treatment of type 2 diabetes

DEFF Research Database (Denmark)

Deacon, Carolyn F; Holst, Jens Juul

2010-01-01

data presented at Scientific Meetings and peer-reviewed studies published since 2007. WHAT THE READER WILL GAIN: This article reviews pharmacokinetic and pharmacodynamic characteristics of linagliptin. Linagliptin belongs to a new chemical class of dipeptidyl pepidase-4 (DPP-4) inhibitors, which...... comprise xanthine-based compounds. It is a potent, long-acting inhibitor with high selectivity for DPP-4 versus the related enzymes DPP-8 and DPP-9. The drug has modest oral availability in humans, but is absorbed rapidly to inhibit plasma DPP-4 activity by > 80% over 24 h. It is not metabolized...

Diet rich in high glucoraphanin broccoli reduces plasma LDL cholesterol: Evidence from randomised controlled trials.

Science.gov (United States)

Armah, Charlotte N; Derdemezis, Christos; Traka, Maria H; Dainty, Jack R; Doleman, Joanne F; Saha, Shikha; Leung, Wing; Potter, John F; Lovegrove, Julie A; Mithen, Richard F

2015-05-01

Cruciferous-rich diets have been associated with reduction in plasma LDL-cholesterol (LDL-C), which may be due to the action of isothiocyanates derived from glucosinolates that accumulate in these vegetables. This study tests the hypothesis that a diet rich in high glucoraphanin (HG) broccoli will reduce plasma LDL-C. One hundred and thirty volunteers were recruited to two independent double-blind, randomly allocated parallel dietary intervention studies, and were assigned to consume either 400 g standard broccoli or 400 g HG broccoli per week for 12 weeks. Plasma lipids were quantified before and after the intervention. In study 1 (37 volunteers), the HG broccoli diet reduced plasma LDL-C by 7.1% (95% CI: -1.8%, -12.3%, p = 0.011), whereas standard broccoli reduced LDL-C by 1.8% (95% CI +3.9%, -7.5%, ns). In study 2 (93 volunteers), the HG broccoli diet resulted in a reduction of 5.1% (95% CI: -2.1%, -8.1%, p = 0.001), whereas standard broccoli reduced LDL-C by 2.5% (95% CI: +0.8%, -5.7%, ns). When data from the two studies were combined the reduction in LDL-C by the HG broccoli was significantly greater than standard broccoli (p = 0.031). Evidence from two independent human studies indicates that consumption of high glucoraphanin broccoli significantly reduces plasma LDL-C. © 2015 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Virological failure of staggered and simultaneous treatment interruption in HIV patients who began Efavirenz-based regimens after allergic reactions to nevirapine

Directory of Open Access Journals (Sweden)

Siripassorn Krittaecho

2013-01-01

Full Text Available Abstract Objective The objective of this work was to study the virological outcomes associated with two different types of treatment interruption strategies in patients with allergic reactions to nevirapine (NVP. We compared the virological outcomes of (1 HIV-1-infected patients who discontinued an initial NVP-based regimen because of cutaneous allergic reactions to NVP; different types of interruption strategies were used, and second-line regimen was based on efavirenz (EFV; and (2 HIV-1-infected patients who began an EFV-based regimen as a first-line therapy (controls. Methods This retrospective cohort included patients who began an EFV-based regimen, between January 2002 and December 2008, as either an initial regimen or as a subsequent regimen after resolving a cutaneous allergic reaction against an initial NVP-based regimen. The study ended in March 2010. The primary outcome was virological failure, which was defined as either (a two consecutive plasma HIV-1 RNA levels >400 copies/mL or (b a plasma HIV-1 RNA level >1,000 copies/mL plus any genotypic resistance mutation. Results A total of 559 patients were stratified into three groups: (a Simultaneous Interruption, in which the subjects simultaneously discontinued all the drugs in an NVP-based regimen following an allergic reaction (n=161; (b Staggered Interruption, in which the subjects discontinued NVP treatment while continuing nucleoside reverse transcriptase inhibitor (NRTI backbone therapy for a median of 7 days (n=82; and (c Control, in which the subjects were naïve to antiretroviral therapy (n=316. The overall median follow-up time was 43 months. Incidence of virological failure in Simultaneous Interruption was 12.9 cases per 1,000 person-years, which trended toward being higher than the incidences in Staggered Interruption (5.4 and Control (6.6. However, differences were not statistically significant. Conclusions Among the patients who had an acute allergic reaction to first

A nomogram to estimate the HbA1c response to different DPP-4 inhibitors in type 2 diabetes: a systematic review and meta-analysis of 98 trials with 24 163 patients

Science.gov (United States)

Esposito, Katherine; Chiodini, Paolo; Maiorino, Maria Ida; Capuano, Annalisa; Cozzolino, Domenico; Petrizzo, Michela; Bellastella, Giuseppe; Giugliano, Dario

2015-01-01

Objectives To develop a nomogram for estimating the glycated haemoglobin (HbA1c) response to different dipeptidyl peptidase-4 (DPP-4) inhibitors in type 2 diabetes. Design A systematic review and meta-analysis of randomised controlled trials (RCTs) of DPP-4 inhibitors (vildagliptin, sitagliptin, saxagliptin, linagliptin and alogliptin) on HbA1c were conducted. Electronic searches were carried out up to December 2013. Trials were included if they were carried out on participants with type 2 diabetes, lasted at least 12 weeks, included at least 30 participants and had a final assessment of HbA1c. A random effect model was used to pool data. A nomogram was used to represent results of the metaregression model. Participants Adults with type 2 diabetes. Interventions Any DPP-4 inhibitor (vildagliptin, sitagliptin, saxagliptin, linagliptin or alogliptin). Outcome measures The HbA1c response to each DPP-4 inhibitor within 1 year of therapy. Results We screened 928 citations and reviewed 98 articles reporting 98 RCTs with 100 arms in 24 163 participants. There were 26 arms with vildagliptin, 37 with sitagliptin, 13 with saxagliptin, 13 with linagliptin and 11 with alogliptin. For all 100 arms, the mean baseline HbA1c value was 8.05% (64 mmol/mol); the decrease of HbA1c from baseline was −0.77% (95% CI −0.82 to −0.72%), with high heterogeneity (I2=96%). Multivariable metaregression model that included baseline HbA1c, type of DPP-4 inhibitor and fasting glucose explained 58% of variance between studies, with no significant interaction between them. Other factors, including age, previous diabetes drugs and duration of treatment added low predictive power (HbA1c reduction from baseline using the type of DPP-4 inhibitor, baseline values of HbA1c and fasting glucose. Conclusions Baseline HbA1c level and fasting glucose explain most of the variance in HbA1c change in response to DPP-4 inhibitors: each increase of 1.0% units HbA1c provides a 0.4–0.5% units greater

Comparative gene expression analysis of Dtg, a novel target gene of Dpp signaling pathway in the early Drosophila melanogaster embryo.

Science.gov (United States)

Hodar, Christian; Zuñiga, Alejandro; Pulgar, Rodrigo; Travisany, Dante; Chacon, Carlos; Pino, Michael; Maass, Alejandro; Cambiazo, Verónica

2014-02-10

In the early Drosophila melanogaster embryo, Dpp, a secreted molecule that belongs to the TGF-β superfamily of growth factors, activates a set of downstream genes to subdivide the dorsal region into amnioserosa and dorsal epidermis. Here, we examined the expression pattern and transcriptional regulation of Dtg, a new target gene of Dpp signaling pathway that is required for proper amnioserosa differentiation. We showed that the expression of Dtg was controlled by Dpp and characterized a 524-bp enhancer that mediated expression in the dorsal midline, as well as, in the differentiated amnioserosa in transgenic reporter embryos. This enhancer contained a highly conserved region of 48-bp in which bioinformatic predictions and in vitro assays identified three Mad binding motifs. Mutational analysis revealed that these three motifs were necessary for proper expression of a reporter gene in transgenic embryos, suggesting that short and highly conserved genomic sequences may be indicative of functional regulatory regions in D. melanogaster genes. Dtg orthologs were not detected in basal lineages of Dipterans, which unlike D. melanogaster develop two extra-embryonic membranes, amnion and serosa, nevertheless Dtg orthologs were identified in the transcriptome of Musca domestica, in which dorsal ectoderm patterning leads to the formation of a single extra-embryonic membrane. These results suggest that Dtg was recruited as a new component of the network that controls dorsal ectoderm patterning in the lineage leading to higher Cyclorrhaphan flies, such as D. melanogaster and M. domestica. Copyright © 2013 Elsevier B.V. All rights reserved.

Nevirapine Concentration in Hair Samples Is a Strong Predictor of Virologic Suppression in a Prospective Cohort of HIV-Infected Patients.

Directory of Open Access Journals (Sweden)

Sanjiv M Baxi

Full Text Available Effective antiretroviral (ARV therapy depends on adequate drug exposure, yet methods to assess ARV exposure are limited. Concentrations of ARV in hair are the product of steady-state pharmacokinetics factors and longitudinal adherence. We investigated nevirapine (NVP concentrations in hair as a predictor of treatment response in women receiving ARVs. In participants of the Women's Interagency HIV Study, who reported NVP use for >1 month from 2003-2008, NVP concentrations in hair were measured via liquid-chromatography-tandem mass-spectrometry. The outcome was virologic suppression (plasma HIV RNA below assay threshold at the time of hair sampling and the primary predictor was nevirapine concentration categorized into quartiles. We controlled for age, race/ethnicity, pre-treatment HIV RNA, CD4 cell count, and self-reported adherence over the 6-month visit interval (categorized ≤ 74%, 75%-94% or ≥ 95%. We also assessed the relation of NVP concentration with changes in hepatic transaminase levels via multivariate random intercept logistic regression and linear regression analyses. 271 women contributed 1089 person-visits to the analysis (median 3 of semi-annual visits. Viral suppression was least frequent in concentration quartile 1 (86/178 (48.3% and increased in higher quartiles (to 158/204 (77.5% for quartile 4. The odds of viral suppression in the highest concentration quartile were 9.17 times (95% CI 3.2-26, P < 0.0001 those in the lowest. African-American race was associated with lower rates of virologic suppression independent of NVP hair concentration. NVP concentration was not significantly associated with patterns of serum transaminases. Concentration of NVP in hair was a strong independent predictor of virologic suppression in women taking NVP, stronger than self-reported adherence, but did not appear to be strongly predictive of hepatotoxicity.

32 CFR 728.54 - U.S. Public Health Service (USPHS), other than members of the uniformed services.

Science.gov (United States)

2010-07-01

... 32 National Defense 5 2010-07-01 2010-07-01 false U.S. Public Health Service (USPHS), other than... FACILITIES Beneficiaries of Other Federal Agencies § 728.54 U.S. Public Health Service (USPHS), other than... 43 (Contract Health Service Purchase Order for Hospital Services Rendered) or HRSA form 64 (Purchase...

Momentum Injection in Tokamak Plasmas and Transitions to Reduced Transport

International Nuclear Information System (INIS)

Parra, F. I.; Highcock, E. G.; Schekochihin, A. A.; Barnes, M.; Cowley, S. C.

2011-01-01

The effect of momentum injection on the temperature gradient in tokamak plasmas is studied. A plausible scenario for transitions to reduced transport regimes is proposed. The transition happens when there is sufficient momentum input so that the velocity shear can suppress or reduce the turbulence. However, it is possible to drive too much velocity shear and rekindle the turbulent transport. The optimal level of momentum injection is determined. The reduction in transport is maximized in the regions of low or zero magnetic shear.

Identification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for Treating Cancer.

Science.gov (United States)

Burger, Matthew T; Pecchi, Sabina; Wagman, Allan; Ni, Zhi-Jie; Knapp, Mark; Hendrickson, Thomas; Atallah, Gordana; Pfister, Keith; Zhang, Yanchen; Bartulis, Sarah; Frazier, Kelly; Ng, Simon; Smith, Aaron; Verhagen, Joelle; Haznedar, Joshua; Huh, Kay; Iwanowicz, Ed; Xin, Xiaohua; Menezes, Daniel; Merritt, Hanne; Lee, Isabelle; Wiesmann, Marion; Kaufman, Susan; Crawford, Kenneth; Chin, Michael; Bussiere, Dirksen; Shoemaker, Kevin; Zaror, Isabel; Maira, Sauveur-Michel; Voliva, Charles F

2011-10-13

Phosphoinositide-3-kinases (PI3Ks) are important oncology targets due to the deregulation of this signaling pathway in a wide variety of human cancers. Herein we describe the structure guided optimization of a series of 2-morpholino, 4-substituted, 6-heterocyclic pyrimidines where the pharmacokinetic properties were improved by modulating the electronics of the 6-position heterocycle, and the overall druglike properties were fine-tuned further by modification of the 4-position substituent. The resulting 2,4-bismorpholino 6-heterocyclic pyrimidines are potent class I PI3K inhibitors showing mechanism modulation in PI3K dependent cell lines and in vivo efficacy in tumor xenograft models with PI3K pathway deregulation (A2780 ovarian and U87MG glioma). These efforts culminated in the discovery of 15 (NVP-BKM120), currently in Phase II clinical trials for the treatment of cancer.

The effect of DPP-4 inhibition with sitagliptin on incretin secretion and on fasting and postprandial glucose turnover in subjects with impaired fasting glucose

DEFF Research Database (Denmark)

Bock, Gerlies; Man, Chiara Dalla; Micheletto, Francesco

2010-01-01

Abstract Objective: Low Glucagon-like Peptide-1 (GLP-1) concentrations have been observed in impaired fasting glucose (IFG). It is uncertain if these abnormalities contribute directly to the pathogenesis of IFG and impaired glucose tolerance. Dipeptidyl peptidase-4 (DPP-4) inhibitors raise incretin...... period, the mixed meal was repeated. Results: As expected, subjects with IFG who received placebo did not experience any change in glucose concentrations. Despite raising intact GLP-1 concentrations, treatment with sitagliptin did not alter either fasting or postprandial glucose, insulin or C....... Conclusions: DPP-4 inhibition did not alter fasting or postprandial glucose turnover in people with IFG. Low incretin concentrations are unlikely to be involved in the pathogenesis of IFG....

Mothers After Gestational Diabetes in Australia Diabetes Prevention Program (MAGDA-DPP) post-natal intervention

DEFF Research Database (Denmark)

Shih, Sophy T.F.; Davis-Lameloise, Nathalie; Janus, Edward D.

2013-01-01

% for high-risk individuals. Methods/Design: The Mothers After Gestational Diabetes in Australia Diabetes Prevention Program (MAGDA-DPP) is a randomized controlled trial aiming to assess the effectiveness of a structured diabetes prevention intervention for post-GDM women. This trial has an intervention...... calls. A total of 574 women will be recruited, with 287 in each arm. The women will undergo blood tests, anthropometric measurements, and self-reported health status, diet, physical activity, quality of life, depression, risk perception and healthcare service usage, at baseline and 12 months...

Treatment with the dipeptidyl peptidase-4 inhibitor vildagliptin improves fasting islet-cell function in subjects with type 2 diabetes.

Science.gov (United States)

D'Alessio, David A; Denney, Amanda M; Hermiller, Linda M; Prigeon, Ronald L; Martin, Julie M; Tharp, William G; Saylan, Monica Liqueros; He, Yanling; Dunning, Beth E; Foley, James E; Pratley, Richard E

2009-01-01

Dipeptidyl peptidase 4 (DPP-4) inhibitors are proposed to lower blood glucose in type 2 diabetes mellitus (T2DM) by prolonging the activity of the circulating incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1). Consistent with this mechanism of action, DPP-4 inhibitors improve glucose tolerance after meals by increasing insulin and reducing glucagon levels in the plasma. However, DPP-4 inhibitors also reduce fasting blood glucose, an unexpected effect because circulating levels of active GIP and GLP-1 are low in the postabsorptive state. The objective of the study was to examine the effects of DPP-4 inhibition on fasting islet function. We conducted a randomized, double-blind, placebo-controlled trial. The study was performed in General Clinical Research Centers at two University Hospitals. Forty-one subjects with T2DM were treated with metformin or diet, having good glycemic control with glycosylated hemoglobin values of 6.2-7.5%. Subjects were treated with vildagliptin (50 mg twice daily) or placebo for 3 months, followed by a 2-wk washout. Major Outcome Measure: We measured insulin secretion in response to iv glucose and arginine before and after treatment and after drug washout. There were small and comparable reductions in glycosylated hemoglobin in both groups over 3 months. Vildagliptin increased fasting GLP-1 levels in subjects taking metformin, but not those managed with diet, and raised active GIP levels slightly. DPP-4 inhibitor treatment improved the acute insulin and C-peptide responses to glucose (50 and 100% respectively; P fasting conditions. This suggests that DPP-4 inhibition has metabolic benefits in addition to enhancing meal-induced GLP-1 and GIP activity.

Discovery of Selective Nanobodies against α-elapitoxin Dpp2c from Black Mamba through Phage Display Screening

DEFF Research Database (Denmark)

Milbo, Christina; Laustsen, Andreas Hougaard; Lohse, Brian

Feared for its highly neurotoxic venom and rapid attack technique, the Black mamba (Dendroaspis polylepis) is Africa’s largest venomous snake. The clinical manifestations of a bitefrom D. polylepis include flaccid paralysis leading to respiratory failure and death due to postsynaptic blockade of ......-neurotoxins. Here, we report the discovery of selective nanobodies targeting α-elapitoxin Dpp2c from D. polylepis through phage display screening....

Bile Acid Sequestration Reduces Plasma Glucose Levels in db/db Mice by Increasing Its Metabolic Clearance Rate

NARCIS (Netherlands)

Meissner, M.; Herrema, H.J.; Dijk, van Th.; Gerding, A.; Havinga, R.; Boer, T.; Müller, M.R.; Reijngoud, D.J.; Groen, A.K.; Kuipers, F.

2011-01-01

Aims/Hypothesis: Bile acid sequestrants (BAS) reduce plasma glucose levels in type II diabetics and in murine models of diabetes but the mechanism herein is unknown. We hypothesized that sequestrant-induced changes in hepatic glucose metabolism would underlie reduced plasma glucose levels.

A reduced set of gyrofluid equations for plasma flow in a diverging magnetic field

International Nuclear Information System (INIS)

Robertson, Scott

2016-01-01

Plasmas are often generated in a small diameter source with a strong magnetic field and subsequently flow into a region with greater diameter and smaller field. The magnetic mirror force that accelerates plasma in a diverging magnetic field appears in the gyrofluid equations developed for applications to toroidal devices, but this force is often absent from fluid equations. A set of gyrofluid equations with reduced complexity is developed in which drifts are assumed negligible and the mirror force is retained. The Chew–Goldberger–Low equations of state are used for a simple closure. These reduced gyrofluid equations are applied to plasma equilibrium in a magnetic mirror, to acceleration of plasma in a magnetic nozzle, and to space charge neutralization of an ion beam by electrons in a diverging magnetic field. The results from gyrofluid theory are compared with results from drift kinetic theory to find the accuracy of the gyrofluid approximation in these applications.

Electron Bernstein Wave Coupling and Emission Measurements on NSTX

Czech Academy of Sciences Publication Activity Database

Taylor, G.; Diem, S.J.; Caughman, J.; Efthimion, P.; Harvey, R.W.; LeBlanc, B.P.; Philips, C.K.; Preinhaelter, Josef; Urban, Jakub

2006-01-01

Roč. 51, č. 7 (2006), s. 177 ISSN 0003-0503. [Annual Meeting of the Division of Plasma Physics/48th./. Philadelphia, Pennsylvania , 30.10.2006-3.11.2006] Institutional research plan: CEZ:AV0Z20430508 Keywords : Conversion * Emission * Tokamaks * Electron Bernstein waves * Simulation * MAST * NSTX Subject RIV: BL - Plasma and Gas Discharge Physics http://www.aps.org/meet/DPP06/baps/all_DPP06.pdf

Thermal Electron Bernstein Wave Emission Measurements on NST

Czech Academy of Sciences Publication Activity Database

Diem, S.J.; Taylor, G.; Efthimion, P.; LeBlanc, B.P.; Philips, C.K.; Caughman, J.; Wilgen, J.B.; Harvey, R.W.; Preinhaelter, Josef; Urban, Jakub

2006-01-01

Roč. 51, č. 7 (2006), s. 134 ISSN 0003-0503. [Annual Meeting of the Division of Plasma Physics/48th./. Philadelphia, Pennsylvania , 30.10.2006-3.11.2006] Institutional research plan: CEZ:AV0Z20430508 Keywords : Conversion * Emission * Tokamaks * Electron Bernstein waves * Simulation * MAST * NSTX Subject RIV: BL - Plasma and Gas Discharge Physics http://www.aps.org/meet/DPP06/baps/all_DPP06.pdf

Effect of Various EFIT NSTX Equilibria on EBW Simulations

Czech Academy of Sciences Publication Activity Database

Urban, Jakub; Preinhaelter, Josef; Sabbagh, S.; Pavlo, Pavol; Vahala, L.; Vahala, G.

2006-01-01

Roč. 51, č. 7 (2006), QPI.00027 ISSN 0003-0503. [Annual Meeting of the Division of Plasma Physics/48th./. Philadelphia, Pennsylvania , 30.10.2006-3.11.2006] Institutional research plan: CEZ:AV0Z20430508 Keywords : Conversion * Emission * Tokamaks * Electron Bernstein waves * Simulation * MAST * NSTX Subject RIV: BL - Plasma and Gas Discharge Physics http://www.aps.org/meet/DPP06/baps/all_DPP06.pdf

The impact of nevirapine- versus protease inhibitor-based regimens on virological markers of HIV-1 persistence during seemingly suppressive ART.

Science.gov (United States)

Kiselinova, Maja; Anna, Maria; Malatinkova, Eva; Vervish, Karen; Beloukas, Apostolos; Messiaen, Peter; Bonczkowski, Pawel; Trypsteen, Wim; Callens, Steven; Verhofstede, Chris; De Spiegelaere, Ward; Vandekerckhove, Linos

2014-01-01

The source and significance of residual plasma HIV-1 RNA detection during suppressive ART remain controversial. It has been proposed that nevirapine (NVP)-based regimens achieve a greater HIV-1 RNA suppression than regimens containing a protease inhibitor (PI). The aim of this study was to compare the effect of receiving NVP- vs PI-based ART on the virological markers of HIV persistence in peripheral blood. The study population comprised 161 HIV-1 infected patients receiving either NVP-based (n=81) or PI-based (n=80) ART and showing a HIV-1 RNA load stably suppressed ART, with median (IQR) levels of 5 (3-6) and 5 (3-8) copies/mL, respectively. HIV-1 RNA detection was associated with shorter duration of suppressive ART regardless of treatment arm (p=0.007), and lower CD4 nadir (p=0.015). HIV-1 DNA levels were median 282 (120-484) and 213 (87-494) copies/106 PBMCs in the two groups respectively, and were lowest (ART HIV-1 RNA load (p=0.0001). In this comprehensive characterization of patients on long-term suppressive ART, we did not observe evidence for a greater suppressive activity of NVP-based over PI-based therapy on plasma and intracellular markers of virus persistence. Overall excellent correlation was observed between the markers, allowing the identification of a subset of treated patients with low HIV-1 expression as an important cohort for future HIV cure studies.

Plasma-treated Langmuir-Blodgett reduced graphene oxide thin film for applications in biophotovoltaics

Science.gov (United States)

Ibrahim, Siti Aisyah; Jaafar, Muhammad Musoddiq; Ng, Fong-Lee; Phang, Siew-Moi; Kumar, G. Ghana; Majid, Wan Haliza Abd; Periasamy, Vengadesh

2018-01-01

The surface optimization and structural characteristics of Langmuir-Blodgett (LB) reduced graphene oxide thin (rGO) film treated by argon plasma treatment were studied. In this work, six times deposition of rGO was deposited on a clean glass substrate using the LB method. Plasma technique involving a variation of plasma power, i.e., 20, 60, 100 and 140 W was exposed to the LB-rGO thin films under argon ambience. The plasma treatment generally improves the wettability or hydrophilicity of the film surface compared to without treatment. Maximum wettability was observed at a plasma power of 20 W, while also increasing the adhesion of the rGO film with the glass substrate. The multilayer films fabricated were characterized by means of spectroscopic, structural and electrical studies. The treatment of rGO with argon plasma was found to have improved its biocompatibility, and thus its performance as an electrode for biophotovoltaic devices has been shown to be enhanced considerably.

Treatment of chronic hemodialysis patients with low-dose fenofibrate effectively reduces plasma lipids and affects plasma redox status

Directory of Open Access Journals (Sweden)

Makówka Agnieszka

2012-07-01

in case of plasma homocysteine. The study shows that a treatment with reduced fenofibrate dose is safe and effective in reducing serum triglycerides and cholesterol in chronic dialysis patients and may shift plasma aminothiol balance towards a more antioxidative pattern.

A Protein Extract from Chicken Reduces Plasma Homocysteine in Rats

Directory of Open Access Journals (Sweden)

Vegard Lysne

2015-06-01

Full Text Available The present study aimed to evaluate effects of a water-soluble protein fraction of chicken (CP, with a low methionine/glycine ratio, on plasma homocysteine and metabolites related to homocysteine metabolism. Male Wistar rats were fed either a control diet with 20% w/w casein as the protein source, or an experimental diet where 6, 14 or 20% w/w of the casein was replaced with the same amount of CP for four weeks. Rats fed CP had reduced plasma total homocysteine level and markedly increased levels of the choline pathway metabolites betaine, dimethylglycine, sarcosine, glycine and serine, as well as the transsulfuration pathway metabolites cystathionine and cysteine. Hepatic mRNA level of enzymes involved in homocysteine remethylation, methionine synthase and betaine-homocysteine S-methyltransferase, were unchanged, whereas cystathionine gamma-lyase of the transsulfuration pathway was increased in the CP treated rats. Plasma concentrations of vitamin B2, folate, cobalamin, and the B-6 catabolite pyridoxic acid were increased in the 20% CP-treated rats. In conclusion, the CP diet was associated with lower plasma homocysteine concentration and higher levels of serine, choline oxidation and transsulfuration metabolites compared to a casein diet. The status of related B-vitamins was also affected by CP.

Experimental treatment of pancreatic cancer with two novel histone deacetylase inhibitors

Science.gov (United States)

Haefner, Martin; Bluethner, Thilo; Niederhagen, Manuel; Moebius, Christian; Wittekind, Christian; Mossner, Joachim; Caca, Karel; Wiedmann, Marcus

2008-01-01

AIM: To investigate in vitro and in vivo treatment with histone deacetylase inhibitors NVP-LAQ824 and NVP-LBH589 in pancreatic cancer. METHODS: Cell-growth inhibition by NVP-LAQ824 and NVP-LBH589 was studied in vitro in 8 human pancreatic cancer cell lines using the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, the anti-tumoral effect of NVP-LBH589 was studied in a chimeric mouse model. Anti-tumoral activity of the drugs was assessed by immunoblotting for p21WAF-1, acH4, cell cycle analysis, TUNEL assay, and immunohistochemistry for MIB-1. RESULTS: In vitro treatment with both compounds significantly suppressed the growth of all cancer cell lines and was associated with hyperacetylation of nucleosomal histone H4, increased expression of p21WAF-1, cell cycle arrest at G2/M-checkpoint, and increased apoptosis. In vivo, NVP-LBH589 alone significantly reduced tumor mass and potentiated the efficacy of gemcitabine. Further analysis of the tumor specimens revealed slightly increased apoptosis and no significant reduction of cell proliferation. CONCLUSION: Our findings suggest that NVP-LBH589 and NVP-LAQ824 are active against human pancreatic cancer, although the precise mechanism of in vivo drug action is not yet completely understood. Therefore, further preclinical and clinical studies for the treatment of pancreatic cancer are recommended. PMID:18595135

Accuracy of a dual path platform (DPP assay for the rapid point-of-care diagnosis of human leptospirosis.

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Scott A Nabity

Full Text Available Diagnosis of leptospirosis by the gold standard serologic assay, the microscopic agglutination test (MAT, requires paired sera and is not widely available. We developed a rapid assay using immunodominant Leptospira immunoglobulin-like (Lig proteins in a Dual Path Platform (DPP. This study aimed to evaluate the assay's diagnostic performance in the setting of urban transmission.We determined test sensitivity using 446 acute and convalescent sera from MAT-confirmed case-patients with severe or mild leptospirosis in Brazil. We assessed test specificity using 677 sera from the following groups: healthy residents of a Brazilian slum with endemic transmission, febrile outpatients from the same slum, healthy blood donors, and patients with dengue, hepatitis A, and syphilis. Three operators independently interpreted visual results without knowing specimen status.The overall sensitivity for paired sera was 100% and 73% for severe and mild disease, respectively. In the acute phase, the assay achieved a sensitivity of 85% and 64% for severe and mild leptospirosis, respectively. Within seven days of illness onset, the assay achieved a sensitivity of 77% for severe disease and 60% for mild leptospirosis. Sensitivity of the DPP assay was similar to that for IgM-ELISA and increased with both duration of symptoms (chi-square regression P = 0.002 and agglutinating titer (Spearman ρ = 0.24, P<0.001. Specificity was ≥93% for dengue, hepatitis A, syphilis, febrile outpatients, and blood donors, while it was 86% for healthy slum residents. Inter-operator agreement ranged from very good to excellent (kappa: 0.82-0.94 and test-to-test reproducibility was also high (kappa: 0.89.The DPP assay performed acceptably well for diagnosis of severe acute clinical leptospirosis and can be easily implemented in hospitals and health posts where leptospirosis is a major public health problem. However, test accuracy may need improvement for mild disease and early stage

A rat retinal damage model predicts for potential clinical visual disturbances induced by Hsp90 inhibitors

International Nuclear Information System (INIS)

Zhou, Dan; Liu, Yuan; Ye, Josephine; Ying, Weiwen; Ogawa, Luisa Shin; Inoue, Takayo; Tatsuta, Noriaki; Wada, Yumiko; Koya, Keizo; Huang, Qin; Bates, Richard C.; Sonderfan, Andrew J.

2013-01-01

In human trials certain heat shock protein 90 (Hsp90) inhibitors, including 17-DMAG and NVP-AUY922, have caused visual disorders indicative of retinal dysfunction; others such as 17-AAG and ganetespib have not. To understand these safety profile differences we evaluated histopathological changes and exposure profiles of four Hsp90 inhibitors, with or without clinical reports of adverse ocular effects, using a rat retinal model. Retinal morphology, Hsp70 expression (a surrogate marker of Hsp90 inhibition), apoptotic induction and pharmacokinetic drug exposure analysis were examined in rats treated with the ansamycins 17-DMAG and 17-AAG, or with the second-generation compounds NVP-AUY922 and ganetespib. Both 17-DMAG and NVP-AUY922 induced strong yet restricted retinal Hsp70 up-regulation and promoted marked photoreceptor cell death 24 h after the final dose. In contrast, neither 17-AAG nor ganetespib elicited photoreceptor injury. When the relationship between drug distribution and photoreceptor degeneration was examined, 17-DMAG and NVP-AUY922 showed substantial retinal accumulation, with high retina/plasma (R/P) ratios and slow elimination rates, such that 51% of 17-DMAG and 65% of NVP-AUY922 present at 30 min post-injection were retained in the retina 6 h post-dose. For 17-AAG and ganetespib, retinal elimination was rapid (90% and 70% of drugs eliminated from the retina at 6 h, respectively) which correlated with lower R/P ratios. These findings indicate that prolonged inhibition of Hsp90 activity in the eye results in photoreceptor cell death. Moreover, the results suggest that the retina/plasma exposure ratio and retinal elimination rate profiles of Hsp90 inhibitors, irrespective of their chemical class, may predict for ocular toxicity potential. - Highlights: • In human trials some Hsp90 inhibitors cause visual disorders, others do not. • Prolonged inhibition of Hsp90 in the rat eye results in photoreceptor cell death. • Retina/plasma ratio and retinal

Fish protein hydrolysate elevates plasma bile acids and reduces visceral adipose tissue mass in rats

DEFF Research Database (Denmark)

Liaset, Bjørn; Madsen, Lise; Hao, Qin

2009-01-01

levels relative to rats fed soy protein or casein. Concomitantly, the saithe FPH fed rats had reduced liver lipids and fasting plasma TAG levels. Furthermore, visceral adipose tissue mass was reduced and expression of genes involved in fatty acid oxidation and energy expenditure was induced in perirenal....../retroperitoneal adipose tissues of rats fed saithe FPH. Our results provide the first evidence that dietary protein sources with different amino acid compositions can modulate the level of plasma bile acids and our data suggest potential novel mechanisms by which dietary protein sources can affect energy metabolism....

Morphology impact on oxygen sensing ability of Ru(dpp){sub 3}Cl{sub 2} containing biocompatible polymers

Energy Technology Data Exchange (ETDEWEB)

Zhao, Susan Y.; Harrison, Benjamin S., E-mail: bharriso@wakehealth.edu

2015-08-01

Especially for tissue engineering applications, the diffusion of oxygen is a critical factor affecting spatial distribution and migration of cells. The cellular oxygen demand also fluctuates depending on tissue type and growth phase. Sensors that determine dissolved oxygen levels under biological conditions provide critical metabolic information about the growing cells as well as the state of the tissue culture within the tissue scaffold. This work focused on the effect of the scaffold morphology on the oxygen sensing response time. It was found that electrospun scaffolds had a faster oxygen-sensing response time than their bulk film counterparts. Tris-(4,7-diphenyl-1,10-phenanthroline) ruthenium (II) dichloride doped electrospun fiber mats of polycaprolactone (PCL) were found to be the most responsive to the presence of oxygen, followed by polyethylene (PEO) glycol mats. Systems containing poly vinyl alcohol were found to be the least responsive. This would suggest that, out of all the polymers tested, PCL and PEO are the most suitable biomaterials for oxygen-sensing applications. - Highlights: • Ru(DPP){sub 3}Cl{sub 2} was blended into common biocompatible polymers such as PEO, PCL, and PVA. • Oxygen sensing was more responsive when polymers were electrospun compared to bulk. • Electrospun PEO and PCL with Ru(dpp){sub 3}Cl{sub 2} showed similar oxygen sensing responses. • PVA showed a slight improvement in oxygen sensing rate when electrospun.

Efficacious and safe management of type 2 diabetes mellitus using DPP-4 inhibitors

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Alexander Sergeevich Ametov

2010-06-01

Full Text Available Diabetes mellitus (DM is believed to be the third most frequent direct cause of death after cardiovascular and oncological diseases. Therefore, solutionof DM-related problems is a major challenge facing health authorities in many countries. No doubt, strict control of glycemia is an indispensablecondition for the reduction of the frequency of diabetic complications. Indeed, many strategies developed in the recent years allowed metabolic controlin DM patients to be significantly improved. Basic and clinical research of the last decade provided a basis for the development of highly promisingtrends in the treatment of CD2, such as the use of incretins. Inhibitors of dipeptylpeptidase-4 (DPP-4 including Galvus (vildagliptin and GalvusMet (vildagliptin + metformin have been available in this country for the last 2 years. International studies showed high efficiency and safety of bothagents. They help to achieve adequate glycemic control in the absence of side effects and complications. Galvus significantly reduces daily variabilityof glycemia that is known to be a risk factor of severe vascular complications of DM. Another advantage of these drugs is they can be used by agedpatients at risk of cardiovascular disorders suffering hypertension. An example of combined therapy using Galvus Met in a DM2 patient is presenteddemonstrating markedly improved glycemic control, blood glucose dynamics, and quality of life. Galvus and Galvus Met can be prescribed as aninitial treatment in combination with all traditional oral hypoglycemic agents and insulin.

Vildagliptin, but not glibenclamide, increases circulating endothelial progenitor cell number: a 12-month randomized controlled trial in patients with type 2 diabetes.

Science.gov (United States)

Dei Cas, Alessandra; Spigoni, Valentina; Cito, Monia; Aldigeri, Raffaella; Ridolfi, Valentina; Marchesi, Elisabetta; Marina, Michela; Derlindati, Eleonora; Aloe, Rosalia; Bonadonna, Riccardo C; Zavaroni, Ivana

2017-02-23

Fewer circulating endothelial progenitor cells (EPCs) and increased plasma (C-term) stromal cell-derived factor 1α (SDF-1α), a substrate of DPP-4, are biomarkers, and perhaps mediators, of cardiovascular risk and mortality. Short-term/acute treatment with DPP-4 inhibitors improve EPC bioavailability; however, long-term effects of DPP-4i on EPCs bioavailability/plasma (C-term) SDF-1α are unknown. Randomized (2:1) open-label trial to compare the effects of vildagliptin (V) (100 mg/day) vs glibenclamide (G) (2.5 mg bid to a maximal dose of 5 mg bid) on circulating EPC levels at 4 and 12 months of treatment in 64 patients with type 2 diabetes in metformin failure. At baseline, and after 4 and 12 months, main clinical/biohumoral parameters, inflammatory biomarkers, concomitant therapies, EPC number (CD34 + /CD133 + /KDR + /10 6 cytometric events) and plasma (C-term) SDF-1α (R&D system) were assessed. Baseline characteristics were comparable in the two groups. V and G similarly and significantly (p < 0.0001) improved glucose control. At 12 months, V significantly increased EPC number (p < 0.05) and significantly reduced (C-term) SDF-1α plasma levels (p < 0.01) compared to G, with no differences in inflammatory biomarkers. V exerts a long-term favorable effect on EPC and (C-term) SDF-1α levels at glucose equipoise, thereby implying a putative beneficial effect on vascular integrity. Trial registration Clinical Trials number: NCT01822548; name: Effect of Vildagliptin vs. Glibenclamide on Circulating Endothelial Progenitor Cell Number Type 2 Diabetes. Registered 28 March, 2013.

Plasma parameter estimations for the Large Helical Device based on the gyro-reduced Bohm scaling

International Nuclear Information System (INIS)

Okamoto, Masao; Nakajima, Noriyoshi; Sugama, Hideo.

1991-10-01

A model of gyro-reduced Bohm scaling law is incorporated into a one-dimensional transport code to predict plasma parameters for the Large Helical Device (LHD). The transport code calculations reproduce well the LHD empirical scaling law and basic parameters and profiles of the LHD plasma are calculated. The amounts of toroidal currents (bootstrap current and beam-driven current) are also estimated. (author)

Estimation of plasma ion saturation current and reduced tip arcing using Langmuir probe harmonics.

Science.gov (United States)

Boedo, J A; Rudakov, D L

2017-03-01

We present a method to calculate the ion saturation current, I sat , for Langmuir probes at high frequency (>100 kHz) using the harmonics technique and we compare that to a direct measurement of I sat . It is noted that the I sat estimation can be made directly by the ratio of harmonic amplitudes, without explicitly calculating T e . We also demonstrate that since the probe tips using the harmonic method are oscillating near the floating potential, drawing little power, this method reduces tip heating and arcing and allows plasma density measurements at a plasma power flux that would cause continuously biased tips to arc. A multi-probe array is used, with two spatially separated tips employing the harmonics technique and measuring the amplitude of at least two harmonics per tip. A third tip, located between the other two, measures the ion saturation current directly. We compare the measured and calculated ion saturation currents for a variety of plasma conditions and demonstrate the validity of the technique and its use in reducing arcs.

Peptide degradation and the role of DPP-4 inhibitors in the treatment of type 2 diabetes

DEFF Research Database (Denmark)

Deacon, Carolyn F

2018-01-01

-1 is an intestinal hormone with potent insulinotropic and glucagonostatic effects and can normalise blood glucose levels in patients with type 2 diabetes, but the native peptide is not therapeutically useful because of its inherent metabolic instability. Using the GLP-1/DPP-4 system and type 2...... diabetes as an example, this review summarises how knowledge of a peptide's biological effects coupled with an understanding of the pathways involved in its metabolic clearance can be exploited in a rational, step-by-step manner to develop a therapeutic agent, which is effective and well tolerated, and any...

Evidence for reduced arterial plasma input, prolonged lung retention and reduced lung monoamine oxidase in smokers

International Nuclear Information System (INIS)

Logan, Jean; Fowler, Joanna S.

2005-01-01

We have previously found that smokers have reduced brain monoamine oxidase (MAO) A and B using positron emission tomography (PET) and the irreversible mechanism-based radiotracers [ 11 C]-labeled clorgyline (CLG) and deprenyl (DEP) and their deuterated analogs (D CLG, D DEP). More recently, we have estimated MAO A and B activity in other organs using the deuterium isotope effect to determine binding specificity for MAO and a three-compartment model to estimate k 3 , the model term proportional to MAO A activity. Here, we have investigated the robustness of the model term k 3 for estimating lung MAO A and B in light of our unexpected finding that lung MAO activity (k 3 ) was reduced for smokers relative to nonsmokers, although radiotracer uptake in the lungs was similar at peak and plateau for the two groups. Methods: Time-activity data from lung and arterial plasma were used from seven nonsmokers and seven smokers scanned previously with CLG and D CLG, and five nonsmokers and nine smokers scanned previously with DEP and D DEP. The measured time-activity curves for lung and plasma and the integrals for the arterial plasma time-activity curves were compared at an early time point (2.5 min) and at the end of the study (55 min). A three-compartment irreversible model was used to estimate the differences between smokers and nonsmokers, and the stability of the parameter (k 3 ) while varying model assumptions for the relative fractions of lung tissue, blood and air in the PET voxel. Results: The peak in the arterial plasma input function and the integral of the arterial plasma time-activity curve over the first 2.5 min after radiotracer injection were significantly lower for smokers relative to nonsmokers for all four tracers. However, although the peak and plateau of the lung time-activity curves were similar for smokers and nonsmokers, the decline in radioactivity from peak to plateau was slower for smokers for all tracers. Using a three-compartment irreversible model

Fresh Water Cyanobacteria Geitlerinema sp. CCC728 and Arthrospira sp. CCC729 as an Anticancer Drug Resource

OpenAIRE

Srivastava, Akanksha; Tiwari, Ratnakar; Srivastava, Vikas; Singh, Tej Bali; Asthana, Ravi Kumar

2015-01-01

An increasing number of cancer patients worldwide, especially in third world countries, have raised concern to explore natural drug resources, such as the less explored fresh water filamentous cyanobacteria. Six strains of cyanobacteria (Phormidium sp. CCC727, Geitlerinema sp. CCC728, Arthrospira sp. CCC729, Phormidium sp. CCC731, Phormidium sp. CCC730, and Leptolyngbya sp. CCC732) were isolated (paddy fields and ponds in the Banaras Hindu University, campus) and five strains screened for ant...

Anti-HIV drugs nevirapine and efavirenz affect anxiety-related behavior and cognitive performance in mice.

Science.gov (United States)

Romão, Pedro R T; Lemos, Joelson C; Moreira, Jeverson; de Chaves, Gisele; Moretti, Morgana; Castro, Adalberto A; Andrade, Vanessa M; Boeck, Carina R; Quevedo, João; Gavioli, Elaine C

2011-01-01

Nevirapine (NVP) and efavirenz (EFV) belong to the class of anti-HIV drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs), commonly used as part of highly active antiretroviral therapy (HAART). Although the HAART is able to bring down viral load to undetectable levels and restore immune function, their prolonged use causes several adverse effects. It has been demonstrated that both NVP and EFV are able to cross the blood-brain barrier, causing important central nervous system-related side effects. Thus, this study investigated the effects of chronic administration of EFV (10 mg/kg) and NVP (3.3 mg/kg) in mice submitted to two distinct series of experiments, which aimed to evaluate: (1) the emotional behavior (elevated plus-maze, forced swimming, and open-field test) and (2) the cognitive performance (object recognition and inhibitory avoidance test) of mice. Our results demonstrated that EFV, but not NVP, reduced the exploration to open arms in the elevated plus-maze test. Neither NVP nor EFV altered mouse behavior in the forced swimming and open-field tests. Both drugs reduced the recognition index in the object recognition test, but only EFV significantly impaired the aversive memory assessed in the inhibitory avoidance test 24 h after training. In conclusion, our findings point to a genuine anxiogenic-like effect to EFV, since it reduced exploration to open arms of elevated plus-maze test without affecting spontaneous locomotion. Additionally, both drugs impaired recognition memory, while only the treatment with EFV impaired significantly aversive memory.

A Phospholipid-Protein Complex from Krill with Antioxidative and Immunomodulating Properties Reduced Plasma Triacylglycerol and Hepatic Lipogenesis in Rats

Directory of Open Access Journals (Sweden)

Marie S. Ramsvik

2015-07-01

Full Text Available Dietary intake of marine omega-3 polyunsaturated fatty acids (n-3 PUFAs can change the plasma profile from atherogenic to cardioprotective. In addition, there is growing evidence that proteins of marine origin may have health benefits. We investigated a phospholipid-protein complex (PPC from krill that is hypothesized to influence lipid metabolism, inflammation, and redox status. Male Wistar rats were fed a control diet (2% soy oil, 8% lard, 20% casein, or diets where corresponding amounts of casein and lard were replaced with PPC at 3%, 6%, or 11% (wt %, for four weeks. Dietary supplementation with PPC resulted in significantly lower levels of plasma triacylglycerols in the 11% PPC-fed group, probably due to reduced hepatic lipogenesis. Plasma cholesterol levels were also reduced at the highest dose of PPC. In addition, the plasma and liver content of n-3 PUFAs increased while n-6 PUFAs decreased. This was associated with increased total antioxidant capacity in plasma and increased liver gene expression of mitochondrial superoxide dismutase (Sod2. Finally, a reduced plasma level of the inflammatory mediator interleukin-2 (IL-2 was detected in the PPC-fed animals. The present data show that PPC has lipid-lowering effects in rats, and may modulate risk factors related to cardiovascular disease progression.

Dapagliflozin Compared to DPP-4 inhibitors is Associated with Lower Risk of Cardiovascular Events and All-cause Mortality in Type 2 Diabetes Patients (CVD-REAL Nordic)

DEFF Research Database (Denmark)

Persson, F; Nyström, Thomas; Jørgensen, Marit Eika

2018-01-01

AIMS: To compare the sodium glucose-cotransporter-2-inhibitor (SGLT-2i) dapagliflozin versus dipeptidyl peptidase-4 inhibitors (DPP-4i) regarding risk associations of MACE (nonfatal myocardial infarction, nonfatal stroke or cardiovascular [CV] mortality), hospital events for heart failure (HHF), ...

In Vitro Dialysis of Cytokine-Rich Plasma With High and Medium Cut-Off Membranes Reduces Its Procalcific Activity.

Science.gov (United States)

Willy, Kevin; Hulko, Michael; Storr, Markus; Speidel, Rose; Gauss, Julia; Schindler, Ralf; Zickler, Daniel

2017-09-01

Recently developed high-flux (HF) dialysis membranes with extended permeability provide better clearance of middle-sized molecules such as interleukins (ILs). Whether this modulation of inflammation influences the procalcific effects of septic plasma on vascular smooth muscle cells (VSMCs) is not known. To assess the effects of high cut-off (HCO) and medium cut-off (MCO) membranes on microinflammation and in vitro vascular calcification we developed a miniature dialysis model. Plasma samples from lipopolysaccharide-spiked blood were dialyzed with HF, HCO, and MCO membranes in an in vitro miniature dialysis model. Afterwards, IL-6 concentrations were determined in dialysate and plasma. Calcifying VSMCs were incubated with dialyzed plasma samples and vascular calcification was assessed. Osteopontin (OPN) and matrix Gla protein (MGP) were measured in VSMC supernatants. IL-6 plasma concentrations were markedly lower with HCO and MCO dialysis. VSMC calcification was significantly lower after incubation with MCO- and HCO-serum compared to HF plasma. MGP and OPN levels in supernatants were significantly lower in the MCO but not in the HCO group compared to HF. In vitro dialysis of cytokine-enriched plasma samples with MCO and HCO membranes reduces IL-6 levels. The induction of vascular calcification by cytokine-enriched plasma is reduced after HCO and MCO dialysis. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Effects of the current boundary conditions at the plasma-gun gap on density in SSPX

Science.gov (United States)

Kolesnikov, Roman; Lodestro, L. L.; Meyer, W. H.

2012-10-01

The Sustained Spheromak Physics Experiment (SSPX) was a toroidal magnetic-confinement device without toroidal magnetic-field coils or a central transformer but which generated core-plasma currents by dynamo processes driven by coaxial plasma-gun injection into a flux-conserving vessel. Record electron temperatures in a spheromak (Te˜500eV) were achieved, and final results of the SSPX program were reported in [1]. Plasma density, which depended strongly on wall conditions, was an important parameter in SSPX. It was observed that density rises with Igun and that confinement improved as the density was lowered. Shortly after the last experiments, a new feature was added to the Corsica code's solver used to reconstruct SSPX equilibria. Motivated by n=0 fields observed in NIMROD simulations of SSPX, an insulating boundary condition was implemented at the plasma-gun gap. Using this option we will perform new reconstructions of SSPX equilibria and look for correlations between the location of the separatrix (which moves up the gun wall and onto the insulating gap as Igun increases) and plasma density and magnetic-flux amplification [2].[4pt] [1] H. S. McLean, APS, DPP, Dallas, TX, 2008.[0pt] [2] E. B. Hooper et al., Nucl. Fusion 47, 1064 (2007).

High-nitrate vegetable diet increases plasma nitrate and nitrite concentrations and reduces blood pressure in healthy women.

Science.gov (United States)

Ashworth, Ann; Mitchell, Klaus; Blackwell, Jamie R; Vanhatalo, Anni; Jones, Andrew M

2015-10-01

Epidemiological studies suggest that green leafy vegetables, which are high in dietary nitrate, are protective against CVD such as stroke. High blood pressure (BP) is a major risk factor for stroke and inorganic nitrate has been shown to reduce BP. The objective of the present study was to test the hypothesis that diets containing high-nitrate (HN) vegetables would increase plasma nitrate and nitrite concentrations and reduce BP in healthy women. A randomized, crossover trial, where participants received HN vegetables (HN diet) or avoided HN vegetables (Control diet) for 1 week. Before and after each intervention, resting BP and plasma nitrate and nitrite concentrations were measured. University of Exeter, UK. Nineteen healthy women (mean age 20 (sd 2) years; mean BMI 22·5 (sd 3·8) kg/m2). The HN diet significantly increased plasma nitrate concentration (before HN diet: mean 24·4 (sd 5·6) µmol/l; after HN diet: mean 61·0 (sd 44·1) µmol/l, Pdiet: mean 98 (sd 91) nmol/l; after HN diet: mean 185 (sd 34) nmol/l, Pdiet. The HN diet significantly reduced resting systolic BP (before HN diet: mean 107 (sd 9) mmHg; after HN diet: mean 103 (sd 6) mmHg, Pdiet (before Control diet: mean 106 (sd 8) mmHg; after Control diet: mean 106 (sd 8) mmHg). Consumption of HN vegetables significantly increased plasma nitrate and nitrite concentrations and reduced BP in normotensive women.

Plasma-induced high efficient synthesis of boron doped reduced graphene oxide for supercapacitors

DEFF Research Database (Denmark)

Li, Shaobo; Wang, Zhaofeng; Jiang, Hanmei

2016-01-01

In this work, we presented a novel route to synthesize boron doped reduced graphene oxide (rGO) by using the dielectric barrier discharge (DBD) plasma technology under ambient conditions. The doping of boron (1.4 at%) led to a significant improvement in the capacitance of rGO and supercapacitors ...

n-3 fatty acids reduce plasma 20-hydroxyeicosatetraenoic acid and blood pressure in patients with chronic kidney disease.

Science.gov (United States)

Barden, Anne E; Burke, Valerie; Mas, Emilie; Beilin, Lawrence J; Puddey, Ian B; Watts, Gerald F; Irish, Ashley B; Mori, Trevor A

2015-09-01

Metabolism of arachidonic acid by cytochrome P450 ω-hydroxylase leads to the formation of 20-hydroxyeicosatetraenoic acid (20-HETE) that regulates vascular function, sodium homeostasis and blood pressure (BP). Supplementation with n-3 fatty acids is known to alter arachidonic acid metabolism and reduce the formation of the lipid peroxidation products F2-isoprostanes, but the effect of n-3 fatty acids on 20-HETE has not been studied. We previously reported a significant effect of n-3 fatty acids but not coenzyme Q10 (CoQ) to reduce BP in a double-blind, placebo-controlled intervention, wherein patients with chronic kidney disease (CKD) were randomized to n-3 fatty acids (4 g), CoQ (200 mg), both supplements or control (4 g olive oil), daily for 8 weeks. This study examined the effect of n-3 fatty acids on plasma and urinary 20-HETE in the same study, as well as plasma and urinary F2-isoprostanes, and relate these to changes in BP. Seventy-four patients completed the 8-week intervention. n-3 fatty acids but not CoQ significantly reduced plasma 20-HETE (P = 0.001) and F2-isoprostanes (P fatty acids. This is the first report that n-3 fatty acid supplementation reduces plasma 20-HETE in humans and that this associates with reduced BP. These results provide a plausible mechanism for the reduction in BP observed in patients with CKD following n-3 fatty acid supplementation.

Dipeptidyl peptidase-4 impairs insulin signaling and promotes lipid accumulation in hepatocytes

International Nuclear Information System (INIS)

Rufinatscha, Kerstin; Radlinger, Bernhard; Dobner, Jochen; Folie, Sabrina; Bon, Claudia; Profanter, Elisabeth; Ress, Claudia; Salzmann, Karin; Staudacher, Gabriele; Tilg, Herbert; Kaser, Susanne

2017-01-01

Dipeptidyl-peptidase 4 [DPP-4) has evolved into an important target in diabetes therapy due to its role in incretin hormone metabolism. In contrast to its systemic effects, cellular functions of membranous DPP-4 are less clear. Here we studied the role of DPP-4 in hepatic energy metabolism. In order to distinguish systemic from cellular effects we established a cell culture model of DPP-4 knockdown in human hepatoma cell line HepG2. DPP-4 suppression was associated with increased basal glycogen content due to enhanced insulin signaling as shown by increased phosphorylation of insulin-receptor substrate 1 (IRS-1), protein kinase B/Akt and mitogen-activated protein kinases (MAPK)/ERK, respectively. Additionally, glucose-6-phosphatase cDNA expression was significantly decreased in DPP-4 deficiency. Reduced triglyceride content in DPP-4 knockdown cells was paralleled by enhanced expressions of peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase −1 (CPT-1) while sterol regulatory element-binding protein 1c (SREBP-1c) expression was significantly decreased. Our data suggest that hepatic DPP-4 induces a selective pathway of insulin resistance with reduced glycogen storage, enhanced glucose output and increased lipid accumulation in the liver. Hepatic DPP-4 might be a novel target in fatty liver disease in patients with glucose intolerance. - Highlights: • DPP-IV knockdown results in increased insulin signaling in hepatocytes. • Increased fatty acid oxidation and decreased lipogenesis result in reduced hepatic triglyceride content in DPP-IV deficiency. • Hepatic DPP-IV induces a selective pathway of insulin resistance with increased triglyceride accumulation in the liver.

Mothers After Gestational Diabetes in Australia Diabetes Prevention Program (MAGDA-DPP) post-natal intervention: an update to the study protocol for a randomized controlled trial.

Science.gov (United States)

Shih, Sophy T F; Davis-Lameloise, Nathalie; Janus, Edward D; Wildey, Carol; Versace, Vincent L; Hagger, Virginia; Asproloupos, Dino; O'Reilly, Sharleen L; Phillips, Paddy A; Ackland, Michael; Skinner, Timothy; Oats, Jeremy; Carter, Rob; Best, James D; Dunbar, James A

2014-06-30

The Mothers After Gestational Diabetes in Australia Diabetes Prevention Program (MAGDA-DPP) is a randomized controlled trial (RCT) that aims to assess the effectiveness of a structured diabetes prevention intervention for women who had gestational diabetes. The original protocol was published in Trials (http://www.trialsjournal.com/content/14/1/339). This update reports on an additional exclusion criterion and change in first eligibility screening to provide greater clarity. The new exclusion criterion "surgical or medical intervention to treat obesity" has been added to the original protocol. The risks of developing diabetes will be affected by any medical or surgical intervention as its impact on obesity will alter the outcomes being assessed by MAGDA-DPP. The screening procedures have also been updated to reflect the current recruitment operation. The first eligibility screening is now taking place either during or after pregnancy, depending on recruitment strategy. Australian New Zealand Clinical Trials Registry ANZCTRN 12610000338066.

Good performance of an immunoassay based method for nevirapine measurements in human breast milk

DEFF Research Database (Denmark)

Salado-Rasmussen, Kirsten; Persson Theilgaard, Zahra; Chiduo, Mercy

2011-01-01

, developed and validated for plasma use. In this study, the ARK NVP-test was evaluated for measurement of nevirapine concentrations in breast milk. High performance liquid chromatography (HPLC) is the method currently used to determine nevirapine in breast milk. This method, however, requires complicated...

Compact, rugged in-chamber transmission spectrometers (7-28 keV) for the Sandia Z facility.

Science.gov (United States)

Sinars, D B; Wenger, D F; Pikuz, S A; Jones, B; Geissel, M; Hansen, S B; Coverdale, C A; Ampleford, D J; Cuneo, M E; McPherson, L A; Rochau, G A

2011-06-01

We describe a pair of time-integrated transmission spectrometers that are designed to survey 7-28 keV (1.9 to 0.43 Å) x-ray photons produced by experiments on the Sandia Z pulsed power facility. Each spectrometer uses a quartz 10-11 crystal in a Cauchois geometry with a slit to provide spatial resolution along one dimension. The spectrometers are located in the harsh environment of the Z vacuum chamber, which necessitates that their design be compact and rugged. Example data from calibration tests and Z experiments are shown that illustrate the utility of the instruments. © 2011 American Institute of Physics

Reduced, three-dimensional, nonlinear equations for high-β plasmas including toroidal effects

International Nuclear Information System (INIS)

Schmalz, R.

1980-11-01

The resistive MHD equations for toroidal plasma configurations are reduced by expanding to the second order in epsilon, the inverse aspect ratio, allowing for high β = μsub(o)p/B 2 of order epsilon. The result is a closed system of nonlinear, three-dimensional equations where the fast magnetohydrodynamic time scale is eliminated. In particular, the equation for the toroidal velocity remains decoupled. (orig.)

Frequent Cross-Resistance to Dapivirine in HIV-1 Subtype C-Infected Individuals after First-Line Antiretroviral Therapy Failure in South Africa.

Science.gov (United States)

Penrose, Kerri J; Wallis, Carole L; Brumme, Chanson J; Hamanishi, Kristen A; Gordon, Kelley C; Viana, Raquel V; Harrigan, P Richard; Mellors, John W; Parikh, Urvi M

2017-02-01

A vaginal ring containing dapivirine (DPV) has shown moderate protective efficacy against HIV-1 acquisition, but the activity of DPV against efavirenz (EFV)- and nevirapine (NVP)-resistant viruses that could be transmitted is not well defined. We investigated DPV cross-resistance of subtype C HIV-1 from individuals on failing NVP- or EFV-containing antiretroviral therapy (ART) in South Africa. Plasma samples were obtained from individuals with >10,000 copies of HIV RNA/ml and with HIV-1 containing at least one non-nucleoside reverse transcriptase (NNRTI) mutation. Susceptibility to NVP, EFV, and DPV in TZM-bl cells was determined for recombinant HIV-1 LAI containing bulk-amplified, plasma-derived, full-length reverse transcriptase sequences. Fold change (FC) values were calculated compared with a composite 50% inhibitory concentration (IC 50 ) from 12 recombinant subtype C HIV-1 LAI plasma-derived viruses from treatment-naive individuals in South Africa. A total of 25/100 (25%) samples showed >500-FCs to DPV compared to treatment-naive samples with IC 50 s exceeding the maximum DPV concentration tested (132 ng/ml). A total of 66/100 (66%) samples displayed 3- to 306-FCs, with a median IC 50 of 17.6 ng/ml. Only 9/100 (9%) samples were susceptible to DPV (FC 500-fold resistance to DPV compared to samples with a ≤500-fold resistance. A total of 91% of samples with NNRTI-resistant HIV-1 from individuals on failing first-line ART in South Africa exhibited ≥3-fold cross-resistance to DPV. This level of resistance exceeds expected plasma concentrations, but very high genital tract DPV concentrations from DPV ring use could block viral replication. It is critically important to assess the frequency of transmitted and selected DPV resistance in individuals using the DPV ring. Copyright © 2017 American Society for Microbiology.

Protein-mediated antagonism between HIV reverse transcriptase ligands nevirapine and MgATP.

Science.gov (United States)

Zheng, Xunhai; Mueller, Geoffrey A; DeRose, Eugene F; London, Robert E

2013-06-18

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) play a central role in the treatment of AIDS, but their mechanisms of action are incompletely understood. The interaction of the NNRTI nevirapine (NVP) with HIV-1 reverse transcriptase (RT) is characterized by a preference for the open conformation of the fingers/thumb subdomains, and a reported variation of three orders of magnitude between the binding affinity of NVP for RT in the presence or absence of primer/template DNA. To investigate the relationship between conformation and ligand binding, we evaluated the use of methionine NMR probes positioned near the tip of the fingers or thumb subdomains. Such probes would be expected to be sensitive to changes in the local environment depending on the fractions of open and closed RT. Comparisons of the NMR spectra of three conservative mutations, I63M, L74M, and L289M, indicated that M63 showed the greatest shift sensitivity to the addition of NVP. The exchange kinetics of the M63 resonance are fast on the chemical shift timescale, but become slow in the presence of NVP due to the slow binding of RT with the inhibitor. The simplest model consistent with this behavior involves a rapid open/closed equilibrium coupled with a slow interaction of the inhibitor with the open conformation. Studies of RT in the presence of both NVP and MgATP indicate a strong negative cooperativity. Binding of MgATP reduces the fraction of RT bound to NVP, as indicated by the intensity of the NVP-perturbed M230 resonance, and enhances the dissociation rate constant of the NVP, resulting in an increase of the open/closed interconversion rate, so that the M63 resonance moves into the fast/intermediate-exchange regime. Protein-mediated interactions appear to explain most of the affinity variation of NVP for RT. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Surplus dietary tryptophan reduces plasma cortisol and noradrenaline concentrations and enhances recovery after social stress in pigs.

Science.gov (United States)

Koopmans, Sietse Jan; Ruis, Marko; Dekker, Ruud; van Diepen, Hans; Korte, Mechiel; Mroz, Zdzislaw

2005-07-21

Social stress occurs in intensive pig farming due to aggressive behavior. This stress may be reduced at elevated dietary levels of tryptophan (TRP). In this study, we compared the effects of high (13.2%) vs. normal (3.4%) dietary TRP to large neutral amino acid (LNAA) ratios on behavior and stress hormones in catheterized pigs ( approximately 50 kg BW), which were exposed to social stress by placing them twice into the territory of a dominant pig ( approximately 60 kg) for 15 min. Pre-stress plasma TRP concentrations were 156+/-15 vs. 53+/-6 micromol/l (psocial confrontations, pigs on the high vs. normal TRP diets show a tendency towards reduced active avoidance behavior (3.2+/-1.1 vs. 6.7+/-1.2 min, psocial confrontations, the post-stress plasma cortisol, noradrenaline and adrenaline concentrations and/or curves (from +5 min to 2 h) were lower/steeper (psurplus TRP in diets for pigs (1) does not significantly affect behavior when exposed to social stress, (2) reduces basal plasma cortisol and noradrenaline concentrations, (3) does not affect the immediate hormonal response to stress, and (4) reduces the long-term hormonal response to stress. In general, pigs receiving high dietary TRP were found to be less affected by stress.

Plasma-mediated vascular dysfunction in the reduced uterine perfusion pressure model of preeclampsia: a microvascular characterization.

LENUS (Irish Health Repository)

Walsh, Sarah K

2012-01-31

Preeclampsia is associated with widespread maternal vascular dysfunction, which is thought to be mediated by circulating factor(s). The aim of the study was to characterize vascular function in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia and to investigate the role of plasma factors in mediating any observed changes in vascular reactivity. Mean arterial blood pressure and vascular function were measured in RUPP and control rats. Mesenteric vessels from both virgin and pregnant rats were exposed for 1 hour or overnight to plasma from both RUPP and control rats and their vascular function assessed. RUPP rats were characterized by severe hypertension, restricted fetal growth, and reduced placental weight (P<0.001). Vasorelaxation was impaired in resistance vessels from RUPP compared with control rats (acetylcholine: R(max) 70+\\/-3 versus 92+\\/-1 [NP] and 93+\\/-3% [sham], P<0.01; bradykinin: 40+\\/-2 versus 62+\\/-2 [NP] and 59+\\/-4% [sham], P<0.001). Incubation of vessels from pregnant (but not virgin) animals with RUPP plasma overnight resulted in an attenuation of vasorelaxant responses (acetylcholine: 63+\\/-7 versus 86+\\/-2%, P<0.05; bradykinin: 35+\\/-5 versus 55+\\/-6%, P<0.001). The residual relaxant response in RUPP plasma-treated vessels was not further attenuated after treatment with N(omega)-nitro-l-arginine methyl ester (acetylcholine: 57+\\/-7 versus 63+\\/-7%, ns; bradykinin: 37+\\/-5 versus 35+\\/-5%, ns). The RUPP rat model is characterized by an impaired response to vasodilators which may be attributable to one or more circulating factors. This plasma-mediated endothelial dysfunction appears to be a pregnancy-dependent effect. Furthermore, nitric oxide-mediated vasorelaxation appears to be absent in RUPP plasma-treated vessels.

Vacuum Plasma Spraying W-coated Reduced Activation Structural Steels for Fusion Plasma Facing Components

Energy Technology Data Exchange (ETDEWEB)

Noh, Sanghoon; Kim, Tae Kyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2014-05-15

Tungsten (W) and its alloys are considered as candidate materials for plasma facing materials of the first wall and diverter components in fusion reactor systems because of high sputtering resistance and low tritium retention in a fusion environment. Therefore, it is considered that the joining between W and reduced activation structural steels, and its evaluation, are critical issues for the development of fusion reactors. However, the joining between these materials is a very challenging process because of significant differences in their physical properties, particularly the mismatch of coefficients of thermal expansion (CTE). For instance, the CTE of pure W is known to be about 4.3Χ10{sup -6}K{sup -1}; however, that of martensitic steels reaches over three times, about 12-14Χ10{sup -6}K{sup -1} at room temperature even up to 373K. Nevertheless, several joining techniques have been developed for joining between W and structural steels, such as a vapor deposition method, brazing and diffusion bonding. Meanwhile, vacuum plasma spraying (VPS) is supposed to be one of the prospective methods to fabricate a sufficient W layer on the steel substrates because of the coating of a large area with a relatively high fabricating rate. In this study, the VPS method of W powders on reduced activation steels was employed, and its microstructure and hardness distribution were investigated. ODS ferritic steels and F82H steel were coated by VPS-W, and the microstructure and hardness distribution were investigated. A microstructure analysis revealed that pure W was successfully coated on steel substrates by the VPS process without an intermediate layer, in spite of a mismatch of the CTE between dissimilar materials. After neutron irradiation, irradiation hardening significantly occurred in the VPSW. However, the hardening of VPS-W was lesser than that of bulk W irradiated HFIR at 773K. Substrate materials, ODS ferritic steels, and F82H steel, did not show irradiation hardening

Linking High Risk Postpartum Women with a Technology Enabled Health Coaching Program to Reduce Diabetes Risk and Improve Wellbeing: Program Description, Case Studies, and Recommendations for Community Health Coaching Programs.

Science.gov (United States)

Athavale, Priyanka; Thomas, Melanie; Delgadillo-Duenas, Adriana T; Leong, Karen; Najmabadi, Adriana; Harleman, Elizabeth; Rios, Christina; Quan, Judy; Soria, Catalina; Handley, Margaret A

2016-01-01

Background . Low-income minority women with prior gestational diabetes mellitus (pGDM) or high BMIs have increased risk for chronic illnesses postpartum. Although the Diabetes Prevention Program (DPP) provides an evidence-based model for reducing diabetes risk, few community-based interventions have adapted this program for pGDM women. Methods . STAR MAMA is an ongoing randomized control trial (RCT) evaluating a hybrid HIT/Health Coaching DPP-based 20-week postpartum program for diabetes prevention compared with education from written materials at baseline. Eligibility includes women 18-39 years old, ≥32 weeks pregnant, and GDM or BMI > 25. Clinic- and community-based recruitment in San Francisco and Sonoma Counties targets 180 women. Sociodemographic and health coaching data from a preliminary sample are presented. Results . Most of the 86 women included to date (88%) have GDM, 80% were identified as Hispanic/Latina, 78% have migrant status, and most are Spanish-speaking. Women receiving the intervention indicate high engagement, with 86% answering 1+ calls. Health coaching callbacks last an average of 9 minutes with range of topics discussed. Case studies presented convey a range of emotional, instrumental, and health literacy-related supports offered by health coaches. Discussion . The DPP-adapted HIT/health coaching model highlights the possibility and challenge of delivering DPP content to postpartum women in community settings. This trial is registered with ClinicalTrials.gov NCT02240420.

In vivo dual-delivery of glucagon like peptide-1 (GLP-1) and dipeptidyl peptidase-4 (DPP4) inhibitor through composites prepared by microfluidics for diabetes therapy

Science.gov (United States)

Araújo, F.; Shrestha, N.; Gomes, M. J.; Herranz-Blanco, B.; Liu, D.; Hirvonen, J. J.; Granja, P. L.; Santos, H. A.; Sarmento, B.

2016-05-01

Oral delivery of proteins is still a challenge in the pharmaceutical field. Nanoparticles are among the most promising carrier systems for the oral delivery of proteins by increasing their oral bioavailability. However, most of the existent data regarding nanosystems for oral protein delivery is from in vitro studies, lacking in vivo experiments to evaluate the efficacy of these systems. Herein, a multifunctional composite system, tailored by droplet microfluidics, was used for dual delivery of glucagon like peptide-1 (GLP-1) and dipeptidyl peptidase-4 inhibitor (iDPP4) in vivo. Oral delivery of GLP-1 with nano- or micro-systems has been studied before, but the simultaneous nanodelivery of GLP-1 with iDPP4 is a novel strategy presented here. The type 2 diabetes mellitus (T2DM) rat model, induced through the combined administration of streptozotocin and nicotinamide, a non-obese model of T2DM, was used. The combination of both drugs resulted in an increase in the hypoglycemic effects in a sustained, but prolonged manner, where the iDPP4 improved the therapeutic efficacy of GLP-1. Four hours after the oral administration of the system, blood glucose levels were decreased by 44%, and were constant for another 4 h, representing half of the glucose area under the curve when compared to the control. An enhancement of the plasmatic insulin levels was also observed 6 h after the oral administration of the dual-drug composite system and, although no statistically significant differences existed, the amount of pancreatic insulin was also higher. These are promising results for the oral delivery of GLP-1 to be pursued further in a chronic diabetic model study.

Mechanism-based population pharmacokinetic modelling in diabetes: vildagliptin as a tight binding inhibitor and substrate of dipeptidyl peptidase IV

Science.gov (United States)

Landersdorfer, Cornelia B; He, Yan-Ling; Jusko, William J

2012-01-01

AIMS To assess the pharmacokinetics of vildagliptin at different doses and build a mechanism-based population model that simultaneously describes vildagliptin pharmacokinetics and its effects on DPP-4 activity based on underlying physiology and biology. METHODS Vildagliptin concentrations and DPP-4 activity vs. time from 13 type 2 diabetic patients after oral vildagliptin 10, 25 or 100 mg and placebo twice daily for 28 days were co-modelled. NONMEM VI and S-ADAPT were utilized for population modelling. RESULTS A target-mediated drug disposition (TMDD) model accounting for capacity-limited high affinity binding of vildagliptin to DPP-4 in plasma and tissues had good predictive performance. Modelling the full time course of the vildagliptin-DPP-4 interaction suggested parallel vildagliptin dissociation from DPP-4 by a slow first-order process and hydrolysis by DPP-4 to an inactive metabolite as a disposition mechanism. Due to limited amounts of DPP-4, vildagliptin concentrations increased slightly more than dose proportionally. This newly proposed model and the parameter estimates are supported by published in vitro studies. Mean parameter estimates (inter-individual coefficient of variation) were: non-saturable clearance 36 l h−1 (25%), central volume of distribution 22 l (37%), half-life of dissociation from DPP-4 1.1 h (94%) and half-life of hydrolysis 6.3 h (81%). CONCLUSIONS Vildagliptin is both an inhibitor and substrate for DPP-4. By utilizing the TMDD approach, slow dissociation of vildagliptin from DPP-4 was found in patients and the half-life of hydrolysis by DPP-4 estimated. This model can be used to predict DPP-4 inhibition effects of other dosage regimens and be modified for other DPP-4 inhibitors to differentiate their properties. PMID:22442826

Erythropoietin does not reduce plasma lactate, H⁺, and K⁺ during intense exercise.

Science.gov (United States)

Nordsborg, N B; Robach, P; Boushel, R; Calbet, J A L; Lundby, C

2015-12-01

It is investigated if recombinant human erythropoietin (rHuEPO) treatment for 15 weeks (n = 8) reduces extracellular accumulation of metabolic stress markers such as lactate, H(+) , and K(+) during incremental exhaustive exercise. After rHuEPO treatment, normalization of blood volume and composition by hemodilution preceded an additional incremental test. Group averages were calculated for an exercise intensity ∼80% of pre-rHuEPO peak power output. After rHuEPO treatment, leg lactate release to the plasma compartment was similar to before (4.3 ± 1.6 vs 3.9 ± 2.5 mmol/min) and remained similar after hemodilution. Venous lactate concentration was higher (P release to the plasma compartment after rHuEPO was similar to before (19.6 ± 5.4 vs 17.6 ± 6.0 mmol/min) and remained similar after hemodilution. Nevertheless, venous pH was lower (P release to the plasma compartment after rHuEPO treatment was similar to before (0.8 ± 0.5 vs 0.7 ± 0.7 mmol/min) and remained similar after hemodilution. Additionally, venous K(+) concentrations were similar after vs before rHuEPO (5.3 ± 0.3 vs 5.1 ± 0.4 mM). In conclusion, rHuEPO does not reduce plasma accumulation of lactate, H(+) , and K(+) at work rates corresponding to ∼80% of peak power output. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High precision absolute differential cross-section measurements for proton-proton elastic scattering at 491.9, 575.5, 641.6, 728.2, and 793.0 MeV

International Nuclear Information System (INIS)

Simon, A.J.

1993-07-01

The proton-proton absolute elastic differential cross section, σ pp (θ), has been measured at incident proton beam energies of 491.9, 575.5, 641.6, 728.2, and 793.0 MeV at laboratory scattering angles of ∼15 degree to ∼42 degree with a total uncertainty on the order of 1%. The measurements were made at the Clinton P. Anderson Los Alamos Meson Physics Facility (LAMPF) and employed a new beam counting technique which provided a better overall beam normalization compared to previous experiments of this type. The cross section was measured with CH 2 targets and a primary liquid, LH 2 , target to determine the uncertainties in some systematic corrections. Extreme care was taken to reduce individual systematic errors to less than 0.5%

A new substitute for formalin: Application to embalming cadavers.

Science.gov (United States)

Haizuka, Yoshinori; Nagase, Miki; Takashino, Satoshi; Kobayashi, Yasushi; Fujikura, Yoshihisa; Matsumura, George

2018-01-01

The development of formalin-free fixatives is an urgent issue in gross anatomy because of the health hazard and the tissue-hardening actions of formalin. We recently identified the fixative, antimicrobial, and preservative effects of N-vinyl-2-pyrrolidone (NVP), a precursor of the water-soluble macromolecular polymer polyvinylpyrrolidone, in animal experiments. The aim of the present study is to investigate whether NVP solution can be used as an alternative to formalin in human cadaveric dissection. Twelve donated cadavers were infused with NVP via the femoral and common carotid arteries using a peristaltic pump. Experienced teaching staff members in our department dissected the cadavers and examined their macroanatomical properties. The NVP-embalmed corpses showed no sign of decomposition or fungal growth. The bodies remained soft and flexible. Notably, the shoulder, elbow, wrist, phalangeal, hip, knee, cervical spine, and temporomandibular joints were highly mobile, almost equivalent to those of living individuals. The range of motion of most joints was greater in the NVP-fixed than formalin-fixed cadavers. Under the dermis, the subcutaneous fat was markedly reduced and the connective tissues were transparent, so the ligaments, cutaneous nerves, and veins were easily discernible. The abdominal wall and the visceral organs remained pliable and elastic, resembling those of fresh cadavers. The lungs, liver, and gastrointestinal tract were moveable in the thoracic and abdominal cavities and were readily isolated. NVP can be used successfully as a fixative and preservative solution for human cadavers; furthermore, NVP-embalmed bodies could be valuable for learning clinical skills and for training, and for developing innovative medical devices. Clin. Anat. 31:90-98, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Plasma-induced highly efficient synthesis of boron doped reduced graphene oxide for supercapacitors.

Science.gov (United States)

Li, Shaobo; Wang, Zhaofeng; Jiang, Hanmei; Zhang, Limei; Ren, Jingzheng; Zheng, Mingtao; Dong, Lichun; Sun, Luyi

2016-09-21

In this work, we presented a novel route to synthesize boron doped reduced graphene oxide (rGO) by using the dielectric barrier discharge (DBD) plasma technology under ambient conditions. The doping of boron (1.4 at%) led to a significant improvement in the capacitance of rGO and supercapacitors based on the as-synthesized B-rGO exhibited an outstanding specific capacitance.

Secretion and dipeptidyl peptidase-4-mediated metabolism of incretin hormones after a mixed meal or glucose ingestion in obese compared to lean, nondiabetic men

DEFF Research Database (Denmark)

Carr, Richard D; Larsen, Marianne O; Jelic, Katarina

2010-01-01

Context: Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are cleaved by dipeptidyl peptidase-4 (DPP-4); plasma activity of DPP-4 may be increased in obesity. The impact of this increase on incretin hormone secretion and metabolism is not known. Objective......: The aim of the study was to assess incretin hormone secretion and degradation in lean and obese nondiabetic subjects. Design, Settings, and Participants: We studied the ingestion of a mixed meal (560 kcal) or oral glucose (2 g/kg) in healthy lean (n = 12; body mass index, 20-25 kg/m(2)) or obese (n = 13...... incretin hormones show dissociated changes in obesity: GLP-1 but not GIP secretion is lower after meal ingestion and oral glucose, whereas GIP but not GLP-1 metabolism is increased after meal ingestion. 2) Increased plasma DPP-4 activity in obesity is not associated with a generalized augmented incretin...

Size-dependent mechanical properties of PVA nanofibers reduced via air plasma treatment

International Nuclear Information System (INIS)

Fu Qiang; Song Xuefeng; Gao Jingyun; Han Xiaobing; Zhao Qing; Yu Dapeng; Jin Yu; Jiang Xingyu

2010-01-01

Organic nanowires/fibers have great potential in applications such as organic electronics and soft electronic techniques. Therefore investigation of their mechanical performance is of importance. The Young's modulus of poly(vinyl alcohol) (PVA) nanofibers was analyzed by scanning probe microscopy (SPM) methods. Air plasma treatment was used to reduce the nanofibers to different sizes. Size-dependent mechanical properties of PVA nanofibers were studied and revealed that the Young's modulus increased dramatically when the scales became very small (<80 nm).

Size-dependent mechanical properties of PVA nanofibers reduced via air plasma treatment.

Science.gov (United States)

Fu, Qiang; Jin, Yu; Song, Xuefeng; Gao, Jingyun; Han, Xiaobing; Jiang, Xingyu; Zhao, Qing; Yu, Dapeng

2010-03-05

Organic nanowires/fibers have great potential in applications such as organic electronics and soft electronic techniques. Therefore investigation of their mechanical performance is of importance. The Young's modulus of poly(vinyl alcohol) (PVA) nanofibers was analyzed by scanning probe microscopy (SPM) methods. Air plasma treatment was used to reduce the nanofibers to different sizes. Size-dependent mechanical properties of PVA nanofibers were studied and revealed that the Young's modulus increased dramatically when the scales became very small (<80 nm).

Review and limitations of 3D plasma blob modeling with reduced collisional fluid equations

Energy Technology Data Exchange (ETDEWEB)

Angus, Justin R., E-mail: jangus@ucsd.edu [University of California, San Diego, La Jolla, CA (United States); Umansky, Maxim V. [Lawrence Livermore National Laboratory, Livermore, CA (United States); Krashenninikov, Sergei I. [University of California, San Diego, La Jolla, CA (United States)

2013-07-15

Recent 3D studies on plasma blobs (coherent structures found in the edge region of magnetic confinement devices) have demonstrated that the drift wave instability can strongly limit the blob’s coherency and cross field convective nature that is predicted by 2D theory. However, the dominant unstable drift wave modes that effect plasma blobs were found to exist in parameter regimes that only marginally satisfied several of the major assumptions considered for the validity of the reduced collisional fluid equations used in the study. Namely, the neglect of electron heat flow, finite electron mean free path effects, and thermal ions. A follow up study demonstrated how the drift wave instability might change if a set of equations that does not suffer from the limitations mentioned above were considered. In the present paper, the results of this later work are used to discuss the limitations on using the collisional fluid equations for 3D studies of plasma blobs.

3-D resistive MHD calculations for tokamak plasmas: beyond the simple reduced set of equations

International Nuclear Information System (INIS)

Carreras, B.A.; Garcia, L.; Hender, T.C.; Hicks, H.R.; Holmes, J.A.; Lynch, V.E.; Masden, B.F.

1983-01-01

Numerical studies of the resistive stability of tokamak plasmas in cylindrical geometry have been performed using: (1) the full set of resistive Magnetohydrodynamic (MHD) equations and (2) an extended version of the reduced set of resistive MHD equations including diamagnetic and electron temperature effects. In particular, the nonlinear interaction of tearing modes of many helicities has been investigated. The numerical results confirm many of the features uncovered previously using the simple reduced equations. (author)

A systematic review and meta-analysis of the effect and safety of ginger in the treatment of pregnancy-associated nausea and vomiting.

Science.gov (United States)

Viljoen, Estelle; Visser, Janicke; Koen, Nelene; Musekiwa, Alfred

2014-03-19

Nausea and vomiting during pregnancy (NVP) occur commonly. Possible harmful side-effects of conventional medicine to the fetus create the need for alternative options to relieve NVP. This systematic review (SR) investigated current evidence regarding orally administered ginger for the treatment of NVP. The primary objective was to assess the effectiveness of ginger in treating NVP. The secondary objective was to assess the safety of ginger during pregnancy. A comprehensive electronic bibliographic database search was carried out. Randomized controlled trials (RCTs) of the efficacy of orally administered ginger, as treatment for NVP in pregnant women at any stage of pregnancy, published in English, were included. Two researchers independently extracted data and assessed trial quality. RevMan5 software (Cochrane Collaboration) was used for data analysis. p Ginger significantly improved the symptoms of nausea when compared to placebo (MD 1.20, 95% CI 0.56-1.84, p = 0.0002, I² = 0%). Ginger did not significantly reduce the number of vomiting episodes during NVP, when compared to placebo, although there was a trend towards improvement (MD 0.72, 95% CI -0.03-1.46, p = 0.06, I² = 71%). Subgroup analyses seemed to favor the lower daily dosage of ginger for nausea relief. Ginger did not pose a significant risk for spontaneous abortion compared to placebo (RR 3.14, 95% CI 0.65-15.11, p = 0.15; I² = 0%), or to vitamin B₆ (RR 0.49, 95% CI 0.17-1.42, p = 0.19, I² = 40%). Similarly, ginger did not pose a significant risk for the side-effects of heartburn or drowsiness. This review suggests potential benefits of ginger in reducing nausea symptoms in pregnancy (bearing in mind the limited number of studies, variable outcome reporting and low quality of evidence). Ginger did not significantly affect vomiting episodes, nor pose a risk for side-effects or adverse events during pregnancy. Based on evidence from this SR, ginger could be considered a harmless and possibly

Measured improvement of global magnetohydrodynamic mode stability at high-beta, and in reduced collisionality spherical torus plasmas

Energy Technology Data Exchange (ETDEWEB)

Berkery, J. W.; Sabbagh, S. A.; Balbaky, A. [Department of Applied Physics and Applied Mathematics, Columbia University, New York, New York 10027 (United States); Bell, R. E.; Diallo, A.; Gerhardt, S. P.; LeBlanc, B. P.; Manickam, J.; Menard, J. E.; Podestà, M. [Princeton Plasma Physics Laboratory, Princeton University, Princeton, New Jersey 08543 (United States); Betti, R. [Laboratory for Laser Energetics, University of Rochester, Rochester, New York 14623 (United States)

2014-05-15

Global mode stability is studied in high-β National Spherical Torus Experiment (NSTX) plasmas to avoid disruptions. Dedicated experiments in NSTX using low frequency active magnetohydrodynamic spectroscopy of applied rotating n = 1 magnetic fields revealed key dependencies of stability on plasma parameters. Observations from previous NSTX resistive wall mode (RWM) active control experiments and the wider NSTX disruption database indicated that the highest β{sub N} plasmas were not the least stable. Significantly, here, stability was measured to increase at β{sub N}∕l{sub i} higher than the point where disruptions were found. This favorable behavior is shown to correlate with kinetic stability rotational resonances, and an experimentally determined range of measured E × B frequency with improved stability is identified. Stable plasmas appear to benefit further from reduced collisionality, in agreement with expectation from kinetic RWM stabilization theory, but low collisionality plasmas are also susceptible to sudden instability when kinetic profiles change.

Erythropoietin does not reduce plasma lactate, H+, and K+ during intense exercise

DEFF Research Database (Denmark)

Nordsborg, Nikolai Baastrup; Robach, P; Boushel, R

2015-01-01

It is investigated if recombinant human erythropoietin (rHuEPO) treatment for 15 weeks (n = 8) reduces extracellular accumulation of metabolic stress markers such as lactate, H(+) , and K(+) during incremental exhaustive exercise. After rHuEPO treatment, normalization of blood volume...... and composition by hemodilution preceded an additional incremental test. Group averages were calculated for an exercise intensity ∼80% of pre-rHuEPO peak power output. After rHuEPO treatment, leg lactate release to the plasma compartment was similar to before (4.3 ± 1.6 vs 3.9 ± 2.5 mmol/min) and remained similar...... after hemodilution. Venous lactate concentration was higher (P release to the plasma compartment after rHuEPO was similar to before (19.6 ± 5.4 vs 17.6 ± 6.0 mmol/min) and remained similar after hemodilution. Nevertheless, venous p...

C-13 NMR spectroscopy of plasma reduces interference of hypertriglyceridemia in the H-1 NMR detection of malignancy

International Nuclear Information System (INIS)

Fossell, E.T.; Hall, F.M.; McDonagh, J.

1991-01-01

The authors have previously described the application of water-suppressed proton nuclear magnetic resonance (H-1 NMR) spectroscopy of plasma for detection of malignancy. Subsequently, hypertriglyceridemia has been identified as a source of false positive results. Here is described a confirmatory, adjunctive technique -analysis of the carbon-13 (C-13) NMR spectrum of plasma- which also identifies the presence of malignancy but is not sensitive to the plasma triglyceride level. Blinded plasma samples from 480 normal donors and 208 patients scheduled for breast biopsy were analyzed by water-suppressed H-1 and C-13 NMR spectroscopy. Triglyceride levels were also measured. Among the normal donors, there were 38 individuals with hypertriglyceridemia of whom 18 had results consistent with malignancy by H-1 NMR spectroscopy. However, the C-13 technique reduced the apparent H-1 false positive rate from 7.0 to 0.6 percent. Similarly, in the breast biopsy cohort, C-13 reduced the false positive rate from 2.8 to 0.9 percent. Furthermore, the accuracy of the combined H-1/C-13 test in this blinded study was greater than 96 percent in 208 patients studied. (author). 27 refs.; 5 figs.; 4 tabs

Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207.

Science.gov (United States)

Hitti, Jane; Halvas, Elias K; Zheng, Lu; Panousis, Constantinos G; Kabanda, Joseph; Taulo, Frank; Kumarasamy, Nagalingeswaran; Pape, Jean William; Lalloo, Umesh; Sprenger, Heather; Klingman, Karin L; Chan, Ellen S; McMahon, Deborah; Mellors, John W

2014-11-01

Intrapartum single-dose nevirapine (sdNVP) reduces HIV-1 perinatal transmission but selects NVP resistance among mothers and infants. We evaluated the frequency of antiretroviral resistance among infants with intrauterine HIV-1 infection exposed to sdNVP and maternal antenatal or breastfeeding antiretroviral therapy. This analysis included 429 infants from sub-Saharan Africa, India and Haiti whose 422 mothers received sdNVP plus maternal study treatment. At entry mothers had CD4>250/μL and were ART-naïve except for antenatal ZDV per local standard of care. Maternal study treatment started intrapartum and included ZDV/3TC, TDF/FTC or LPV/r for 7 or 21 days in a randomized factorial design. Infants received sdNVP study treatment and ZDV if local standard of care. Infant HIV RNA or DNA PCR and samples for genotype were obtained at birth and weeks 2, 4 and 12; infants who ever breast-fed were also tested at weeks 16, 24, 48 and 96. Samples from HIV-1-infected infants were tested for drug resistance by population genotype (ViroSeq). NVP or NRTI resistance mutations were assessed using the IAS-USA mutation list. Perinatal HIV-1 transmission occurred in 17 (4.0%) infants including 12 intrauterine infections. Resistance mutations were detected among 5 (42%) intrauterine-infected infants; of these, 3 had mutations conferring resistance to NVP alone, 1 had resistance to NRTI alone, and 1 had dual-class resistance mutations. Among the 2 infants with NRTI mutations, one (K70R) was likely maternally transmitted and one (K65R) occurred in the context of breastfeeding exposure to maternal antiretroviral therapy. Infants with intrauterine HIV infection are at risk of acquiring resistance mutations from exposure to maternal antiretroviral medications intrapartum and/or during breastfeeding. New approaches are needed to lower the risk of antiretroviral resistance in these infants.

Renal effects of DPP-4 inhibitor sitagliptin or GLP-1 receptor agonist liraglutide in overweight patients with type 2 diabetes : A 12-week, randomized, double-blind, placebo-controlled trial

NARCIS (Netherlands)

Tonneijck, Lennart; Smits, Mark M.; Muskiet, Marcel H A; Hoekstra, Trynke; Kramer, Mark H H; Danser, A. H Jan; Ter Wee, Piet M.; Diamant, Michaela; Joles, Jaap A.; Van Raalte, Daniël H.

2016-01-01

OBJECTIVE To investigate effects of dipeptidyl peptidase-4 inhibitor (DPP-4I) sitagliptin or glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide treatment on renal hemodynamics, tubular functions, and markers of renal damage in overweight patients with type 2 diabetes without chronic kidney

Sub therapeutic drug levels among HIV/TB co-infected patients ...

African Journals Online (AJOL)

Daniel W. Gunda

2016-11-01

Nov 1, 2016 ... NVP based regimen was associated with sub-therapeutic drug levels on uni- ... a number of important challenges including induction of sub- therapeutic levels of .... ARV plasma levels in the univariate model with p-values less than 0.05 .... clearance of ARVs.56 This may be one of the explanations that.

Reduced and high molecular weight barley beta-glucans decrease plasma total and non-HDL-cholesterol in hypercholesterolemic Syrian golden hamsters.

Science.gov (United States)

Wilson, Thomas A; Nicolosi, Robert J; Delaney, Bryan; Chadwell, Kim; Moolchandani, Vikas; Kotyla, Timothy; Ponduru, Sridevi; Zheng, Guo-Hua; Hess, Richard; Knutson, Nathan; Curry, Leslie; Kolberg, Lore; Goulson, Melanie; Ostergren, Karen

2004-10-01

Consumption of concentrated barley beta-glucan lowers plasma cholesterol because of its soluble dietary fiber nature. The role of molecular weight (MW) in lowering serum cholesterol is not well established. Prior studies showed that enzymatic degradation of beta-glucan eliminates the cholesterol-lowering activity; however, these studies did not evaluate the MW of the beta-glucan. The current study was conducted to evaluate whether barley beta-glucan concentrates, partially hydrolyzed to reduce MW, possess cholesterol-lowering and antiatherogenic activities. The reduced MW fraction was compared with a high MW beta-glucan concentrate from the same barley flour. Concentrated beta-glucan preparations were evaluated in Syrian Golden F(1)B hamsters fed a hypercholesterolemic diet (HCD) with cholesterol, hydrogenated coconut oil, and cellulose. After 2 wk, hamsters were fed HCD or diets that contained high or reduced MW beta-glucan at a concentration of 8 g/100 g at the expense of cellulose. Decreases in plasma total cholesterol (TC) and non-HDL-cholesterol (non-HDL-C) concentrations occurred in the hamsters fed reduced MW and high MW beta-glucan diets. Plasma HDL-C concentrations did not differ. HCD-fed hamsters had higher plasma triglyceride concentrations. Liver TC, free cholesterol, and cholesterol ester concentrations did not differ. Aortic cholesterol ester concentrations were lower in the reduced MW beta-glucan-fed hamsters. Consumption of either high or reduced MW beta-glucan increased concentrations of fecal total neutral sterols and coprostanol, a cholesterol derivative. Fecal excretion of cholesterol was greater than in HCD-fed hamsters only in those fed the reduced MW beta-glucan. Study results demonstrate that the cholesterol-lowering activity of barley beta-glucan may occur at both lower and higher MW.

Inulin Supplementation Does Not Reduce Plasma Trimethylamine N-Oxide Concentrations in Individuals at Risk for Type 2 Diabetes

Directory of Open Access Journals (Sweden)

Mary Elizabeth Baugh

2018-06-01

Full Text Available Trimethylamine N-oxide (TMAO is associated with type 2 diabetes (T2DM and increased risk of adverse cardiovascular events. Prebiotic supplementation has been purported to reduce TMAO production, but whether prebiotics reduce fasting or postprandial TMAO levels is unclear. Sedentary, overweight/obese adults at risk for T2DM (n = 18 were randomized to consume a standardized diet (55% carbohydrate, 30% fat with 10 g/day of either an inulin supplement or maltodextrin placebo for 6 weeks. Blood samples were obtained in the fasting state and hourly during a 4-h high-fat challenge meal (820 kcal; 25% carbohydrate, 63% fat; 317.4 mg choline, 62.5 mg betaine, 8.1 mg l-carnitine before and after the diet. Plasma TMAO and trimethylamine (TMA moieties (choline, l-carnitine, betaine, and γ-butyrobetaine were measured using isocratic ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS. There were no differences in fasting or postprandial TMAO or TMA moieties between the inulin and placebo groups at baseline (all p > 0.05. There were no significant changes in fasting or postprandial plasma TMAO or TMA moiety concentrations following inulin or placebo. These findings suggest that inulin supplementation for 6 weeks did not reduce fasting or postprandial TMAO in individuals at risk for T2DM. Future studies are needed to identify efficacious interventions that reduce plasma TMAO concentrations.

Dietary copper in excess of nutritional requirement reduces plasma and breast muscle cholesterol of chickens.

Science.gov (United States)

Bakalli, R I; Pesti, G M; Ragland, W L; Konjufca, V

1995-02-01

Male commercial broiler strain chickens were fed from hatching to 42 d of age either a control diet (based on corn and soybean meal) or the control diet supplemented with 250 mg copper/kg diet from cupric sulfate pentahydrate (for 35 or 42 d). Hypocholesterolemia (11.8% reduction) and decreased breast muscle cholesterol (20.4% reduction) were observed in copper-supplemented birds. There was a slight increase (P > .05) in breast muscle copper (14.5%), and all levels were very low (copper for 42 vs 35 d resulted in lower levels of cholesterol in the plasma (12.9 vs 10.8% reduction) and breast muscle (24.6 vs 16.2% reduction). Very similar results were found in two additional experiments in which hypocholesterolemia and reduced breast muscle cholesterol were associated with reduced plasma triglycerides and blood reduced glutathione. It is well known that hypercholesterolemia is a symptom of dietary copper deficiency. The data presented here indicate that blood and breast muscle cholesterol are inversely related to dietary copper in excess of the dietary requirement for maximal growth. The cholesterol content of the edible muscle tissue of broiler chickens can be reduced by approximately 25% after feeding a supranormal level of copper for 42 d without altering the growth of the chickens or substantially increasing the copper content of the edible meat.

Cell-Penetrating CaCO3 Nanocrystals for Improved Transport of NVP-BEZ235 across Membrane Barrier in T-Cell Lymphoma

Science.gov (United States)

Civallero, Monica; Citti, Cinzia; Cosenza, Maria; Baldassarre, Francesca; Cannazza, Giuseppe; Pozzi, Samantha; Sacchi, Stefano

2018-01-01

Owing to their nano-sized porous structure, CaCO3 nanocrystals (CaCO3NCs) hold the promise to be utilized as desired materials for encapsulating molecules which demonstrate wide promise in drug delivery. We evaluate the possibility to encapsulate and release NVP-BEZ235, a novel and potent dual PI3K/mTOR inhibitor that is currently in phase I/II clinical trials for advanced solid tumors, from the CaCO3NCs. Its chemical nature shows some intrinsic limitations which induce to administer high doses leading to toxicity; to overcome these problems, here we proposed a strategy to enhance its intracellular penetration and its biological activity. Pristine CaCO3 NCs biocompatibility, cell interactions and internalization in in vitro experiments on T-cell lymphoma line, were studied. Confocal microscopy was used to monitor NCs-cell interactions and cellular uptake. We have further investigated the interaction nature and release mechanism of drug loaded/released within/from the NCs using an alternative approach based on liquid chromatography coupled to mass spectrometry. Our approach provides a good loading efficiency, therefore this drug delivery system was validated for biological activity in T-cell lymphoma: the anti-proliferative test and western blot results are very interesting because the proposed nano-formulation has an efficiency higher than free drug at the same nominal concentration. PMID:29370086

Chronic Exercise Reduces CETP and Mesterolone Treatment Counteracts Exercise Benefits on Plasma Lipoproteins Profile: Studies in Transgenic Mice.

Science.gov (United States)

Casquero, Andrea Camargo; Berti, Jairo Augusto; Teixeira, Laura Lauand Sampaio; de Oliveira, Helena Coutinho Franco

2017-12-01

Regular exercise and anabolic androgenic steroids have opposing effects on the plasma lipoprotein profile and risk of cardio-metabolic diseases in humans. Studies in humans and animal models show conflicting results. Here, we used a mice model genetically modified to mimic human lipoprotein profile and metabolism. They under-express the endogenous LDL receptor gene (R1) and express a human transgene encoding the cholesteryl ester transfer protein (CETP), normally absent in mice. The present study was designed to evaluate the independent and interactive effects of testosterone supplementation, exercise training and CETP expression on the plasma lipoprotein profile and CETP activity. CETP/R1 and R1 mice were submitted to a 6-week swimming training and mesterolone (MEST) supplementation in the last 3 weeks. MEST treatment increased markedly LDL levels (40%) in sedentary CETP/R1 mice and reduced HDL levels in exercised R1 mice (18%). A multifactorial ANOVA revealed the independent effects of each factor, as follows. CETP expression reduced HDL (21%) and increased non-HDL (15%) fractions. MEST treatment increased the VLDL concentrations (42%) regardless of other interventions. Exercise training reduced triacylglycerol (25%) and free fatty acids (20%), increased both LDL and HDL (25-33%), and reduced CETP (19%) plasma levels. Significant factor interactions showed that the increase in HDL induced by exercise is explained by reducing CETP activity and that MEST blunted the exercise-induced elevation of HDL-cholesterol. These results reinforce the positive metabolic effects of exercise, resolved a controversy about CETP response to exercise and evidenced MEST potency to counteract specific exercise benefits.

Caffeine ingestion after rapid weight loss in judo athletes reduces perceived effort and increases plasma lactate concentration without improving performance.

Science.gov (United States)

Lopes-Silva, Joao P; Felippe, Leandro J C; Silva-Cavalcante, Marcos D; Bertuzzi, Romulo; Lima-Silva, Adriano E

2014-07-22

The objective of this study was to examine the effect of caffeine on judo performance, perceived exertion, and plasma lactate response when ingested during recovery from a 5-day weight loss period. Six judokas performed two cycles of a 5-day rapid weight loss procedure to reduce their body weight by ~5%. After weigh-in, subjects re-fed and rehydrated over a 4-h recovery period. In the third hour of this "loading period", subjects ingested a capsule containing either caffeine (6 mg·kg-1) or placebo. One hour later, participants performed three bouts of a judo fitness test with 5-min recovery periods. Perceived exertion and plasma lactate were measured before and immediately after each test bout. Body weight was reduced in both caffeine and placebo conditions after the weight loss period (-3.9% ± 1.6% and -4.0% ± 2.3% from control, respectively, p caffeine or placebo groups. However, plasma lactate was systemically higher and perceived exertion lower in the subjects who ingested caffeine compared to either the control or placebo subjects (p caffeine did not improve performance during the judo fitness test after a 5-day weight loss period, but reduced perceived exertion and increased plasma lactate.

Development of a P((MAA-co-NVP)-g-EG) Hydrogel Platform for Oral Protein Delivery: Effects of Hydrogel Composition on Environmental Response and Protein Partitioning.

Science.gov (United States)

Steichen, Stephanie; O'Connor, Colleen; Peppas, Nicholas A

2017-01-01

Hydrogels based upon terpolymers of methacrylic acid, N-vinyl pyrrolidone, and poly(ethylene glycol) are developed and characterized for their ability to respond to changes in environmental pH and to partition protein therapeutics of varying molecular weights and isoelectric points. P((MAA-co-NVP)-g-EG) hydrogels are synthesized with PEG-based cross-linking agents of varying length and incorporation densities. The composition is confirmed using FT-IR spectroscopy and shows peak shifts indicating hydrogen bonding. Scanning electron microscopy reveals microparticles with an irregular, planar morphology. The pH-responsive behavior of the hydrogels is confirmed under equilibrium and dynamic conditions, with the hydrogel collapsed at acidic pH and swollen at neutral pH. The ability of the hydrogels to partition model protein therapeutics at varying pH and ionic strength is evaluated using three model proteins: insulin, porcine growth hormone, and ovalbumin. Finally, the microparticles are evaluated for adverse interactions with two model intestinal cell lines and show minimal cytotoxicity at concentrations below 5 mg mL -1 . © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hepatocyte spheroids as a competent in vitro system for drug biotransformation studies: nevirapine as a bioactivation case study.

Science.gov (United States)

Pinheiro, Pedro F; Pereira, Sofia A; Harjivan, Shrika G; Martins, Inês L; Marinho, Aline T; Cipriano, Madalena; Jacob, Cristina C; Oliveira, Nuno G; Castro, Matilde F; Marques, M Matilde; Antunes, Alexandra M M; Miranda, Joana P

2017-03-01

The development of metabolically competent in vitro models is of utmost importance for predicting adverse drug reactions, thereby preventing attrition-related economical and clinical burdens. Using the antiretroviral drug nevirapine (NVP) as a model, this work aimed to validate rat hepatocyte 3D spheroid cultures as competent in vitro systems to assess drug metabolism and bioactivation. Hepatocyte spheroids were cultured for 12 days in a stirred tank system (3D cultures) and exposed to equimolar dosages of NVP and its two major Phase I metabolites, 12-OH-NVP and 2-OH-NVP. Phase I NVP metabolites were detected in the 3D cultures during the whole culture time in the same relative proportions reported in in vivo studies. Moreover, the modulation of SULT1A1 activity by NVP and 2-OH-NVP was observed for the first time, pointing their synergistic effect as a key factor in the formation of the toxic metabolite (12-sulfoxy-NVP). Covalent adducts formed by reactive NVP metabolites with N-acetyl-L-cysteine and bovine serum albumin were also detected by high-resolution mass spectrometry, providing new evidence on the relative role of the reactive NVP metabolites, 12-sulfoxy-NVP, and NVP quinone methide, in toxicity versus excretion pathways. In conclusion, these results demonstrate the validity of the 3D culture system to evaluate drug bioactivation, enabling the identification of potential biomarkers of bioactivation/toxicity, and providing new evidence to the mechanisms underlying NVP-induced toxic events. This model, integrated with the analytical strategies described herein, is of anticipated usefulness to the pharmaceutical industry, as an upstream methodology for flagging drug safety alerts in early stages of drug development.

Preparation of polymethacrylic acid-grafted HEMA/PVP microspheres and preliminary study on basic protein adsorption.

Science.gov (United States)

Gao, Baojiao; Hu, Hongyan; Guo, Jianfeng; Li, Yanbin

2010-06-01

The crosslinked copolymeric microspheres (HEMA/NVP) of N-vinylpyrrolidone (NVP) and 2-hydroxyethyl methacrylate (HEMA) were prepared using inverse suspension polymerization method. Subsequently, the reaction of methacryloyl chloride with the hydroxyl groups on the surfaces of HEMA/NVP microspheres was performed, leading to the introduction of polymerisable double bonds onto the surfaces of microspheres HEMA/NVP. Afterward, methacrylic acid was allowed to be graft-polymerized on microspheres HEMA/NVP in the manner of "grafting from", resulting in the grafted microspheres PMAA-HEMA/NVP. The grafted microspheres PMAA-HEMA/NVP were fully characterized with several means. The graft-polymerization of MAA on microspheres HEMA/NVP was studied in detail, and the optimal reaction conditions were determined. Thereafter, the adsorption property of the grafted microspheres PMAA-HEMA/NVP for lysozyme as a basic protein model was preliminarily examined to explore the feasibility of removing deleterious basic protein such as density lipoprotein from blood. The experimental results indicate that the PMAA grafting degree on microspheres HEMA/NVP is limited because an enwinding polymer layer as a kinetic barrier on the surfaces of HEMA/NVP microspheres will be formed during the graft-polymerization, and block the graft-polymerization. In order to enhance PMAA grafting degree, reaction temperature, monomer concentration and the used amount of initiator should be effectively controlled. The experimental results also reveal that the grafted microspheres PMAA-HEMA/NVP possess very strong adsorption ability for lysozyme by right of strong electrostatic interaction. Copyright 2010 Elsevier B.V. All rights reserved.

Short-term and long-term effects of dipeptidyl peptidase-4 inhibitors in type 2 diabetes mellitus patients with renal impairment: a meta-analysis of randomized controlled trials.

Science.gov (United States)

Li, Ruifei; Wang, Rui; Li, Haixia; Sun, Sihao; Zou, Meijuan; Cheng, Gang

2016-09-01

To assess the short-term and long-term effects of dipeptidyl peptidase-4 (DPP-4) inhibitors in type 2 diabetes mellitus patients with renal impairment, a meta-analysis of randomized clinical trials of DPP-4 inhibitor interventions in type 2 diabetes mellitus patients with renal impairment was performed. PubMed, Embase, Cochrane Library and ClinicalTrials.gov were searched through the end of March 2015. Randomized clinical trials were selected if (1) DPP-4 inhibitors were compared with a placebo or other active-comparators, (2) the treatment duration was ≥12 weeks and (3) data regarding changes in haemoglobin A1c (HbA1c ), changes in fasting plasma glucose or hypoglycaemia and other adverse events were reported. Of 790 studies, ten studies on eight randomized clinical trials were included. Compared with the control group, DPP-4 inhibitors were associated with a greater HbA1c reduction in both the short-term [mean differences (MD) = -0.45, 95% confidence intervals (-0.57, -0.33), p 1] and long-term [MD = -0.33, 95% confidence intervals (-0.63, -0.03), p = 0.03] treatments. However, the long-term greater reduction in HbA1c with DPP-4 inhibitor treatment was only significant when the control treatment comprised placebo plus stable background treatment, but not glipizide plus stable background treatment. DPP-4 inhibitors were associated with a greater fasting plasma glucose reduction [MD = -12.59, 95% confidence intervals (-22.01, -3.17), p = 0.009] over the short-term; however, this effect was not present over the long-term. Regarding the hypoglycaemia adverse events assessment, the long-term treatment data indicated there was no increased risk of hypoglycaemia compared with placebo or active-controlled anti-diabetic drugs. The present meta-analysis confirms that DPP-4 inhibitors are effective and equivalent to other agents in type 2 diabetes mellitus patients with renal impairment. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015

A water-soluble extract of chicken reduced plasma triacylglycerols, but showed no anti-atherosclerotic activity in apoE−/− mice

Directory of Open Access Journals (Sweden)

Rita Vik

2015-08-01

Conclusion: Chicken protein displayed a slight potential to increase mitochondrial fatty acid oxidation and reduce plasma TAG. However, CP did not affect plasma cholesterol levels, inflammation status or atherosclerotic development in apoE−/− mice. Based on these results, dietary intervention with CP does not have sufficient capacity to influence atherosclerotic development in apoE−/− mice.

Effect of dipeptidyl peptidase-4 inhibitors on circulating tumor necrosis factor-α concentrations: A systematic review and meta-analysis of controlled trials.

Science.gov (United States)

Atkin, Stephen L; Katsiki, Niki; Banach, Maciej; Mikhailidis, Dimitri P; Pirro, Matteo; Sahebkar, Amirhossein

2017-09-01

Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control in patients with type 2 diabetes mellitus. There are also reports of an effect of these drugs in reducing inflammation through inhibition of tumor necrosis factor-α (TNF-α) that is an important mediator for several inflammatory processes. The present systematic review and meta-analysis were performed to evaluate the effect of DPP-4 inhibitors on circulating TNF-α levels in T2DM patients. A systematic review and a meta-analysis were undertaken on all controlled trials of DPP-4 inhibitors that included measurement of TNF-α. The search included PubMed-Medline, Scopus, ISI Web of Knowledge and Google Scholar databases. Quantitative data synthesis was performed using a random-effects model, with standardized mean difference (SMD) and 95% confidence interval (CI) as summary statistics. Meta-regression and leave-one-out sensitivity analysis were performed to assess the modifiers of treatment response. Eight eligible articles (6 with sitagliptin and 2 with vildagliptin) comprising 9 treatment arms were selected for this meta-analysis. Meta-analysis suggested a significant reduction of circulating TNF-α concentrations following treatment with DPP-4 inhibitors (SMD: -1.84, 95% CI: -2.88, -0.80, p=0.001). The effect size was robust in the sensitivity analysis and not mainly driven by a single study. A subgroup analysis did not suggest any significant difference between the TNF-α-lowering activity of sitagliptin (SMD: -1.49, 95% CI: -2.89, -0.10) and vildagliptin (SMD: -2.80, 95% CI: -4.98, -0.61) (p=0.326). This meta-analysis of the 8 available controlled trials showed that DPP-4 inhibition in patients with type 2 diabetes mellitus was associated with significant reductions in plasma TNF-α levels with no apparent difference between sitagliptin and vildagliptin. Copyright © 2017 Elsevier Inc. All rights reserved.

Low-dose spironolactone reduces plasma fibulin-1 levels in patients with type 2 diabetes and resistant hypertension

DEFF Research Database (Denmark)

Stolzenburg Oxlund, Christina; Cangemi, Claudia; Henriksen, J E

2015-01-01

Diabetic patients with hypertension are at particularly high risk of vascular damage and consequently cardiovascular and renal disease. Fibulin-1, an extracellular matrix glycoprotein, is increased in arterial tissue and plasma from individuals with type 2 diabetes. This study aimed to evaluate...... whether antihypertensive treatment with spironolactone changes plasma fibulin-1 levels. In a multicenter, double-blind, randomized, placebo-controlled study, 119 patients with type 2 diabetes and resistant hypertension were included. A dose of spironolactone 25 mg or matching placebo was added to previous....... Treatment with low-dose spironolactone reduced plasma fibulin-1 levels in patients with type 2 diabetes and resistant hypertension. This supports the hypothesis that the antihypertensive effect of the mineralocorticoid receptor blocker in part may be due to regression of vascular remodeling....

Reduced absorption and enhanced synthesis of cholesterol in patients with cystic fibrosis: a preliminary study of plasma sterols.

Science.gov (United States)

Gelzo, Monica; Sica, Concetta; Elce, Ausilia; Dello Russo, Antonio; Iacotucci, Paola; Carnovale, Vincenzo; Raia, Valeria; Salvatore, Donatello; Corso, Gaetano; Castaldo, Giuseppe

2016-09-01

Low cholesterol is typically observed in the plasma of patients with cystic fibrosis (CF) contrasting with the subcellular accumulation of cholesterol demonstrated in CF cells and in mice models. However, the homeostasis of cholesterol has not been well investigated in patients with CF. We studied the plasma of 26 patients with CF and 33 unaffected controls campesterol and β-sitosterol as markers of intestinal absorption and lathosterol as a marker of de novo cholesterol biosynthesis by gas chromatography (GC-FID and GC-MS). Plasma campesterol and β-sitosterol results were significantly (p=0.01) lower while plasma lathosterol was significantly higher (p=0.001) in patients with CF as compared to control subjects. Plasma cholesterol results were significantly lower (p=0.01) in CF patients. Our data suggest that the impaired intestinal absorption of exogenous sterols in patients with CF stimulates the endogenous synthesis of cholesterol, but the levels of total cholesterol in plasma remain lower. This may be due to the CFTR dysfunction that reduces cholesterol blood excretion causing the accumulation of cholesterol in liver cells and in other tissues contributing to trigger CF chronic inflammation.

Antioxidant modulation of nevirapine induced hepatotoxicity in rats

Directory of Open Access Journals (Sweden)

Awodele Olufunsho

2015-03-01

Full Text Available HIV/AIDS related mortality has been dramatically reduced by the advent of antiretroviral therapy (ART. However, ART presents with associated adverse effects. One of such adverse effects is hepatotoxicity observed with nevirapine (NVP containing ART. Since previous studies showed that NVP hepatotoxicity may be due to oxidative stress via generation of oxidative radicals, this study sought to evaluate the protective effects of antioxidants in alleviating NVP induced hepatotoxicity. Rats were divided into 6 groups with 8 animals per group and received doses of the antioxidants jobelyn (10.7 mg/kg/day, vitamin C (8 mg/kg/day, vitamin E (5 mg/kg/day and/or NVP (6 mg/kg/day for 60 days. The animals were sacrificed on day 61 by cervical dislocation, blood samples were collected for biochemical and hematological examination. The liver of the sacrificed animals was weighed and subjected to histopathological examination. There was a statistically significant (p<0.05 elevation in MDA level observed in the NVP group as compared with control. The results further showed non-significant decreases in the levels of MDA in the NVP plus antioxidant groups, except vitamin C, when compared with the NVP alone group. Vitamin E and Vitamin E plus C treated groups showed significantly (p<0.05 higher levels of SOD, CAT and GSH. The results also showed statistically significantly (p<0.05 lower levels of ALT and AST in the antioxidant treated groups There was an observed significantly (p<0.05 higher level of TP and urea in the antioxidant treated rats. A significantly (p<0.05 higher white blood cell count was observed in the antioxidant groups. Histopathological assessment of the liver extracted from the rats showed no visible pathology across the groups. Observations from this study suggest a potentially positive modulatory effect of antioxidants and may be indicative for the inclusion of antioxidants in nevirapine containing ART.

Proton and deuteron production in neutron-induced reactions on carbon at En=42.5, 62.7, and 72.8 MeV

International Nuclear Information System (INIS)

Slypen, I.; Corcalciuc, V.; Meulders, J.P.

1995-01-01

Double-differential cross sections for proton and deuteron production in fast neutron induced reactions on carbon are reported for three incident neutron energies: 42.5, 62.7, and 72.8 MeV. Angular distributions were measured at laboratory angles between 20 degree and 160 degree. Procedures for data taking and data reduction are presented. Energy-differential cross sections and total cross sections are also reported. Experimental cross sections are compared with existing data and with theoretical calculations in the frame of the intranuclear cascade model

The importance of high injection velocity to reduce plasma armature growth and drag in hypervelocity railguns

International Nuclear Information System (INIS)

Hawke, R.S.; Dixon, W.R.; Kang, S.W.; McCallen, R.C.; Susoeff, A.R.; Asay, J.R.; Shaninpoor, M.

1987-01-01

Plasmas are required to serve as armature in hypervelocity railguns. Typically, the plasmas are at temperatures of about 20-30,000 K and result in a high heat flux on the barrel wall. Slow moving plasmas radiate heat and melt the launcher wall causing it to ablate and resulting in a growth of the armature mass and length. As the velocity increases, the more massive and longer armature will result in greater viscous drag and ultimately limit the maximum achievable velocity. Several possible means of reducing the armature growth are possible. This paper discusses two of them, use of heat resistant barrel materials, and reduction of wall heating by reduction of exposure time through use of a high initial velocity. A summary of experimentally based, material ablation resistance calculations is presented. Second, the benefit of high injection velocity is evaluated. Finally, a joint SNLA and LLNL railgun research project based on the above considerations are described

Development of Nevirapine Resistance in Children Exposed to the Prevention of Mother-to-Child HIV-1 Transmission Programme in Maputo, Mozambique.

Directory of Open Access Journals (Sweden)

Francisco Antunes

Full Text Available Single-dose nevirapine (sd-NVP has been the main option for prevention of mother-to-child transmission (PMTCT of HIV-1 in low-resource settings. However, sd-NVP can induce the selection of HIV-1 resistant mutations in mothers and infants. In Mozambique, there are limited data regarding the profile of NVP resistance associated mutations (RAM in the context of PMTCT.To assess the prevalence and the factors associated with NVP RAM among children born to HIV-1 infected mothers enrolled in the PMTCT programme adopted in Mozambique.One hundred and fifty seven children aged 6 to 48 weeks were sequentially included (July 2011 to March 2012 at four centres in Maputo. Genotyping of RAM was performed in samples with HIV-1 RNA≥ 100 copies/μL (Viroseq. Sequencing was performed with ABI 3100 (Applied Biosystems. Logistic regression modelling was undertaken to identify the factors associated with NVP RAM.Seventy-nine children had their samples genotyped. Their median age was 7.0 (3-12 months and 92.4% received prophylaxis with sd-NVP at birth plus daily NVP. 35.4% of mothers received antiretrovirals (ARVs for PMTCT. ARV RAM were detected in 43 (54.4% of the children. 45.6% of these children had at least one NVP RAM. The most common mutations associated with NVP resistance were K103N (n = 16 and Y181C (n = 15. NVP RAM was significantly associated with mother exposure to PMTCT (crude odds ratio [OR] 30.3, 95% CI 4.93-186.34 and with mother's CD4 count < 350 cells/mm3 (crude OR 3.08, 95% CI 1.02-9.32. In the multivariable analysis the mother's exposure to PMTCT was the only variable significantly associated with NVP RAM (adjusted OR 48.65, 95% CI 9.33-253.66.We found a high prevalence of NVP RAM among children who were exposed to the drug regimen for PMTCT in Mozambique. The mothers' exposure to PMTCT significantly increased the risk of NVP RAM.

Krill protein hydrolysate reduces plasma triacylglycerol level with concurrent increase in plasma bile acid level and hepatic fatty acid catabolism in high-fat fed mice

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Marie S. Ramsvik

2013-11-01

Full Text Available Background: Krill powder, consisting of both lipids and proteins, has been reported to modulate hepatic lipid catabolism in animals. Fish protein hydrolysate diets have also been reported to affect lipid metabolism and to elevate bile acid (BA level in plasma. BA interacts with a number of nuclear receptors and thus affects a variety of signaling pathways, including very low density lipoprotein (VLDL secretion. The aim of the present study was to investigate whether a krill protein hydrolysate (KPH could affect lipid and BA metabolism in mice. Method: C57BL/6 mice were fed a high-fat (21%, w/w diet containing 20% crude protein (w/w as casein (control group or KPH for 6 weeks. Lipids and fatty acid composition were measured from plasma, enzyme activity and gene expression were analyzed from liver samples, and BA was measured from plasma. Results: The effect of dietary treatment with KPH resulted in reduced levels of plasma triacylglycerols (TAG and non-esterified fatty acids (NEFAs. The KPH treated mice had also a marked increased plasma BA concentration. The increased plasma BA level was associated with induction of genes related to membrane canalicular exporter proteins (Abcc2, Abcb4 and to BA exporters to blood (Abcc3 and Abcc4. Of note, we observed a 2-fold increased nuclear farnesoid X receptor (Fxr mRNA levels in the liver of mice fed KPH. We also observed increased activity of the nuclear peroxiosme proliferator-activated receptor alpha (PPARα target gene carnitine plamitoyltransferase 2 (CPT-2. Conclusion: The KPH diet showed to influence lipid and BA metabolism in high-fat fed mice. Moreover, increased mitochondrial fatty acid oxidation and elevation of BA concentration may regulate the plasma level of TAGs and NEFAs.

Fast plasma shutdown by killer pellet injection in JT-60U with reduced heat flux on the divertor plate and avoiding runaway electron generation

International Nuclear Information System (INIS)

Yoshino, R.; Kondoh, T.; Neyatani, Y.; Itami, K.; Kawano, Y.; Isei, N.

1997-01-01

A killer pellet is an impurity pellet that is injected into a tokamak plasma in order to terminate a discharge without causing serious damage to the tokamak machine. In JT-60U neon ice pellets have been injected into OH and NB heated plasmas and fast plasma shutdowns have been demonstrated without large vertical displacement. The heat pulse on the divertor plate has been greatly reduced by killer pellet injections (KPI), but a low-power heat flux tail with a long time duration is observed. The total energy on the divertor plate increases with longer heat flux tail, so it has been reduced by shortening the tail. Runaway electron (RE) generation has been observed just after KPI and/or in the later phase of the plasma current quench. However, RE generation has been avoided when large magnetic perturbations are excited. These experimental results clearly show that KPI is a credible fast shutdown method avoiding large vertical displacement, reducing heat flux on the divertor plate, and avoiding (or minimizing) RE generation. (Author)

A DOE/Fusion Energy Sciences Research/Education Program at PVAMU Study of Rotamak Plasmas

Energy Technology Data Exchange (ETDEWEB)

Huang, Tian-Sen [Prairie View A& M Univ., Prairie View, TX (United States); Saganti, Premkumar [Prairie View A& M Univ., Prairie View, TX (United States)

2017-02-17

During recent years (2004-2015), with DOE support, the PVAMU plasma research group accomplished new instrumentation development, conducted several new plasma experiments, and is currently poised to advance with standing-wave microwave plasma propulsion research. On the instrumentation development, the research group completed: (i) building a new plasma chamber with metal CF flanges, (ii) setting up of a 6kW/2450MHz microwave input system as an additional plasma heating source at our rotamak plasma facility, (iii) installation of one programmatic Kepco ATE 6-100DMG fast DC current supply system used in rotamak plasma shape control experiment, built a new microwave, standing-wave experiment chamber and (iv) established a new plasma lab with field reversal configuration capability utilizing 1MHz/200kW RF (radio frequency) wave generator. Some of the new experiments conducted in this period also include: (i) assessment of improved magnetic reconnection at field-reversed configuration (FRC) plasma, (ii) introduction of microwave heating experiments, and (iii) suppression of n = 1 tilt instability by one coil with a smaller current added inside the rotamak’s central pipe. These experiments led to publications in Physical Review Letters, Reviews of Scientific Instruments, Division of Plasma Physics (DPP) of American Physical Society (APS) Reports, Physics of Plasmas Controlled Fusion, and Physics of Plasmas (between 2004 and 2015). With these new improvements and advancements, we also initiated and accomplished design and fabrication of a plasma propulsion system. Currently, we are assembling a plasma propulsion experimental system that includes a 5kW helicon plasma source, a 25 cm diameter plasma heating chamber with 1MHz/200kW RF power rotating magnetic field, and a 60 cm diameter plasma exhaust chamber, and expect to achieve a plasma mass flow of 0.1g/s with 60km/s ejection. We anticipate several propulsion applications in near future as we advance our capabilities

Autologous platelet-rich plasma reduces transfusions during ascending aortic arch repair: a prospective, randomized, controlled trial.

Science.gov (United States)

Zhou, Shao Feng; Estrera, Anthony L; Loubser, Paul; Ignacio, Craig; Panthayi, Sreelatha; Miller, Charles; Sheinbaum, Roy; Safi, Hazim J

2015-04-01

Blood conservation using autologous platelet-rich plasma (aPRP), a technique of whole blood harvest that separates red blood cells from plasma and platelets before cardiopulmonary bypass with retransfusion of the preserved platelets after completion of cardiopulmonary bypass, has not been studied extensively. We sought to prospectively determine whether aPRP reduces blood transfusions during ascending and transverse aortic arch repair. We randomly assigned 80 patients undergoing elective ascending and transverse aortic arch repair using deep hypothermic circulatory arrest to receive either aPRP (n = 38) or no aPRP (n = 42). Volume of aPRP retransfused was 726 ± 124 mL. The primary end point was transfusion amount. Secondary end points were death, stroke, renal failure, pulmonary failure, and transfusion costs. Perioperative transfusion rate was defined as blood transfusions given during surgery and up to 72 hours afterward. The surgeon and intensivist were blinded to the treatment arm. Because an anesthesiologist initiated the protocol, the surgeon was not aware of aPRP collection, as this occurred only after the sterile drape was in place. In addition, because cell salvage was performed on all cases, differentiation in perfusionist activities (during spinning of aPRP) was not evident. Platelet, fresh frozen plasma, and cryoprecipitate intraoperative transfusions were performed only after heparin was reversed and the patient was judged as coagulopathic on the basis of associated criteria: cryoprecipitate transfusion for fibrinogen level less than 150 μg/dL, platelet transfusion for platelet count less than 80,000, and fresh frozen plasma when thromboelastogram test was suggestive or a partial thromboplastin time was greater than 55 seconds, and prothrombin time was greater than 1.6 seconds. Early mortality, stroke, and respiratory complications were similar between groups. Only acute renal failure was reduced in the aPRP group, 7% versus 0% (p platelets by 56

Caffeine Ingestion after Rapid Weight Loss in Judo Athletes Reduces Perceived Effort and Increases Plasma Lactate Concentration without Improving Performance

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Joao P. Lopes-Silva

2014-07-01

Full Text Available The objective of this study was to examine the effect of caffeine on judo performance, perceived exertion, and plasma lactate response when ingested during recovery from a 5-day weight loss period. Six judokas performed two cycles of a 5-day rapid weight loss procedure to reduce their body weight by ~5%. After weigh-in, subjects re-fed and rehydrated over a 4-h recovery period. In the third hour of this “loading period”, subjects ingested a capsule containing either caffeine (6 mg·kg−1 or placebo. One hour later, participants performed three bouts of a judo fitness test with 5-min recovery periods. Perceived exertion and plasma lactate were measured before and immediately after each test bout. Body weight was reduced in both caffeine and placebo conditions after the weight loss period (−3.9% ± 1.6% and −4.0% ± 2.3% from control, respectively, p < 0.05. At three hours after weigh-in, body weight had increased with both treatments but remained below the control (−3.0% ± 1.3% and −2.7% ± 2.2%. There were no significant differences in the number of throws between the control, caffeine or placebo groups. However, plasma lactate was systemically higher and perceived exertion lower in the subjects who ingested caffeine compared to either the control or placebo subjects (p < 0.05. In conclusion, caffeine did not improve performance during the judo fitness test after a 5-day weight loss period, but reduced perceived exertion and increased plasma lactate.

PTP1B, α-glucosidase, and DPP-IV inhibitory effects for chromene derivatives from the leaves of Smilax china L.

Science.gov (United States)

Zhao, Bing Tian; Le, Duc Dat; Nguyen, Phi Hung; Ali, Md Yousof; Choi, Jae-Sue; Min, Byung Sun; Shin, Heung Mook; Rhee, Hae Ik; Woo, Mi Hee

2016-06-25

Two new flavonoids, bismilachinone (11) and smilachinin (14), were isolated from the leaves of Smilax china L. together with 14 known compounds. Their structures were elucidated using spectroscopic methods. The PTP1B, α-glucosidase, and DPP-IV inhibitory activities of compounds 1-16 were evaluated at the molecular level. Among them, compounds 4, 7, and 10 showed moderate DPP-IV inhibitory activities with IC50 values of 20.81, 33.12, and 32.93 μM, respectively. Compounds 3, 4, 6, 11, 12, and 16 showed strong PTP1B inhibitory activities, with respective IC50 values of 7.62, 10.80, 0.92, 2.68, 9.77, and 24.17 μM compared with the IC50 value for the positive control (ursolic acid: IC50 = 1.21 μM). Compounds 2-7, 11, 12, 15, and 16 showed potent α-glucosidase inhibitory activities, with respective IC50 values of 8.70, 81.66, 35.11, 35.92, 7.99, 26.28, 11.28, 62.68, 44.32, and 70.12 μM. The positive control, acarbose, displayed an IC50 value of 175.84 μM. In the kinetic study for the PTP1B enzyme, compounds 6, 11, and 12 displayed competitive inhibition with Ki values of 3.20, 8.56, and 5.86 μM, respectively. Compounds 3, 4, and 16 showed noncompetitive inhibition with Ki values of 18.75, 5.95, and 22.86 μM, respectively. Molecular docking study for the competitive inhibitors (6, 11, and 12) radically corroborates the binding affinities and inhibition of PTP1B enzymes. These results indicated that the leaves of Smilax china L. may contain compounds with anti-diabetic activity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Spectral survey of helium lines in a linear plasma device for use in HELIOS imaging

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Ray, H. B.; Biewer, T. M.; Fehling, D. T.; Isler, R. C.; Unterberg, E. A.

2016-11-01

Fast visible cameras and a filterscope are used to examine the visible light emission from Oak Ridge National Laboratory's Proto-MPEX. The filterscope has been configured to perform helium line ratio measurements using emission lines at 667.9, 728.1, and 706.5 nm. The measured lines should be mathematically inverted and the ratios compared to a collisional radiative model (CRM) to determine Te and ne. Increasing the number of measurement chords through the plasma improves the inversion calculation and subsequent Te and ne localization. For the filterscope, one spatial chord measurement requires three photomultiplier tubes (PMTs) connected to pellicle beam splitters. Multiple, fast visible cameras with narrowband filters are an alternate technique for performing these measurements with superior spatial resolution. Each camera contains millions of pixels; each pixel is analogous to one filterscope PMT. The data can then be inverted and the ratios compared to the CRM to determine 2-dimensional "images" of Te and ne in the plasma. An assessment is made in this paper of the candidate He I emission lines for an imaging technique.

Sex differences in hepatic and intestinal contributions to nevirapine biotransformation in rats.

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Pinheiro, P F; Marinho, A T; Antunes, A M M; Marques, M M; Pereira, S A; Miranda, J P

2015-05-25

The understanding of the intestine contribution to drug biotransformation improved significantly in recent years. However, the sources of inter-individual variability in intestinal drug biotransformation, namely sex-differences, are still elusive. Nevirapine (NVP) is an orally taken anti-HIV drug associated with severe idiosyncratic reactions elicited by toxic metabolites, with women at increased risk. As such, NVP is a good model to assess sex-dimorphic metabolism. The aim of this study was to perform a comparative profiling of NVP biotransformation in rat intestine and liver and evaluate whether or not it is organ- and sex-dependent. Therefore, nevirapine-containing solutions were perfused through the intestine, in a specially designed chamber, or incubated with liver slices, from male and female Wistar rats. The levels of NVP and its Phase I metabolites were quantified by HPLC-UV. Liver incubation experiments yielded the metabolites 2-, 3-, 8-, and 12-OH-NVP, being 12-OH-NVP and 2-OH-NVP the major metabolites in males and females, respectively. Inter-sex differences in the metabolic profile were also detected in the intestine perfusion experiments. Herein, the metabolites 3- and 12-OH-NVP were only found in male rats, whereas 2-OH-NVP levels were higher in females, both in extraluminal (pbiotransformation was observed, strengthening the relevance of the intestinal contribution in the biotransformation of orally taken-drugs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

ATP Synthase β-Chain Overexpression in SR-BI Knockout Mice Increases HDL Uptake and Reduces Plasma HDL Level

Directory of Open Access Journals (Sweden)

Kexiu Song

2014-01-01

Full Text Available HDL cholesterol is known to be inversely correlated with cardiovascular disease due to its diverse antiatherogenic functions. SR-BI mediates the selective uptake of HDL-C. SR-BI knockout diminishes but does not completely block the transport of HDL; other receptors may be involved. Ectopic ATP synthase β-chain in hepatocytes has been previously characterized as an apoA-I receptor, triggering HDL internalization. This study was undertaken to identify the overexpression of ectopic ATP synthase β-chain on DIL-HDL uptake in primary hepatocytes in vitro and on plasma HDL levels in SR-BI knockout mice. Human ATP synthase β-chain cDNA was delivered to the mouse liver by adenovirus and GFP adenovirus as control. The adenovirus-mediated overexpression of β-chain was identified at both mRNA and protein levels on mice liver and validated by its increasing of DiL-HDL uptake in primary hepatocytes. In response to hepatic overexpression of β-chain, plasma HDL-C levels and cholesterol were reduced in SR-BI knockout mice, compared with the control. The present data suggest that ATP synthase β-chain can serve as the endocytic receptor of HDL, and its overexpression can reduce plasma HDL-C.

Photophysical Study of DPPTT-T/PC70 BM Blends and Solar Devices as a Function of Fullerene Loading: An Insight into EQE Limitations of DPP-Based Polymers

KAUST Repository

Collado-Fregoso, Elisa

2016-12-27

Diketopyrrolopyrrole (DPP)-based polymers have been consistently used for the fabrication of solar cell devices and transistors due to the existence of intermolecular short contacts, resulting in high electron and hole mobilities. However, they also often show limited external quantum efficiencies (EQEs). In this contribution, the authors analyze the limitations on EQE by a combined study of exciton dissociation efficiency, charge separation, and recombination kinetics in thin films and solar devices of a DPP-based donor polymer, DPPTT-T (thieno[3,2-b]thiophene-diketopyrrolopyrrole copolymer) blended with varying weight fractions of the fullerene acceptor PCBM. From the correlations between photoluminescence quenching, transient absorption studies, and EQE measurements, it is concluded that the main limitation of photon-to-charge conversion in DPPTT-T/PCBM devices is poor exciton dissociation. This exciton quenching limit is related not only to the low affinity/miscibility of the materials, as confirmed by wide angle X-ray diffraction diffraction and transmission electron microscopy data, but also to the relatively short DPPTT-T singlet exciton lifetime, possibly associated with high nonradiative losses. A further strategy to improve EQE in this class of polymers without sacrificing the good extraction properties in optimized blends is therefore to limit those nonradiative decay processes.

Photophysical Study of DPPTT-T/PC70 BM Blends and Solar Devices as a Function of Fullerene Loading: An Insight into EQE Limitations of DPP-Based Polymers

KAUST Repository

Collado-Fregoso, Elisa; Deledalle, Florent; Utzat, Hendrik; Tuladhar, Pabitra S.; Dimitrov, Stoichko D.; Gillett, Alexander; Tan, Ching Hong; Zhang, Weimin; McCulloch, Iain; Durrant, James R.

2016-01-01

Diketopyrrolopyrrole (DPP)-based polymers have been consistently used for the fabrication of solar cell devices and transistors due to the existence of intermolecular short contacts, resulting in high electron and hole mobilities. However, they also often show limited external quantum efficiencies (EQEs). In this contribution, the authors analyze the limitations on EQE by a combined study of exciton dissociation efficiency, charge separation, and recombination kinetics in thin films and solar devices of a DPP-based donor polymer, DPPTT-T (thieno[3,2-b]thiophene-diketopyrrolopyrrole copolymer) blended with varying weight fractions of the fullerene acceptor PCBM. From the correlations between photoluminescence quenching, transient absorption studies, and EQE measurements, it is concluded that the main limitation of photon-to-charge conversion in DPPTT-T/PCBM devices is poor exciton dissociation. This exciton quenching limit is related not only to the low affinity/miscibility of the materials, as confirmed by wide angle X-ray diffraction diffraction and transmission electron microscopy data, but also to the relatively short DPPTT-T singlet exciton lifetime, possibly associated with high nonradiative losses. A further strategy to improve EQE in this class of polymers without sacrificing the good extraction properties in optimized blends is therefore to limit those nonradiative decay processes.

Nevirapine and efavirenz elicit different changes in lipid profiles in antiretroviral-therapy-naive patients infected with HIV-1.

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Frank van Leth

2004-10-01

-c and decreases in TC:HDL-c ratio than an EFV-containing regimen. Based on these findings, protease-inhibitor-sparing regimens based on non-nucleoside reverse transcriptase inhibitor, particularly those containing NVP, may be expected to result in a reduced risk of coronary heart disease.

Transition in plasma fluctuation between attached and detached plasmas

International Nuclear Information System (INIS)

Okazaki, Katsuya; Ohno, Noriyasu; Kajita, Shin; Tanaka, Hirohiko

2012-01-01

The static and dynamic behaviors of detached plasmas have received considerable attention because the use of a detached divertor is thought to provide a promising method for reducing the heat flux to plasma-facing components. In this study, fluctuations were measured with an electrostatic probe as the plasma was changed from attached to detached states by increasing the neutral gas pressure. The transition from an attached plasma to a detached plasma was found to change the phase relation between the density and the potential. (author)

Antisense oligonucleotide inhibition of apolipoprotein C-III reduces plasma triglycerides in rodents, nonhuman primates, and humans.

Science.gov (United States)

Graham, Mark J; Lee, Richard G; Bell, Thomas A; Fu, Wuxia; Mullick, Adam E; Alexander, Veronica J; Singleton, Walter; Viney, Nick; Geary, Richard; Su, John; Baker, Brenda F; Burkey, Jennifer; Crooke, Stanley T; Crooke, Rosanne M

2013-05-24

Elevated plasma triglyceride levels have been recognized as a risk factor for the development of coronary heart disease. Apolipoprotein C-III (apoC-III) represents both an independent risk factor and a key regulatory factor of plasma triglyceride concentrations. Furthermore, elevated apoC-III levels have been associated with metabolic syndrome and type 2 diabetes mellitus. To date, no selective apoC-III therapeutic agent has been evaluated in the clinic. To test the hypothesis that selective inhibition of apoC-III with antisense drugs in preclinical models and in healthy volunteers would reduce plasma apoC-III and triglyceride levels. Rodent- and human-specific second-generation antisense oligonucleotides were identified and evaluated in preclinical models, including rats, mice, human apoC-III transgenic mice, and nonhuman primates. We demonstrated the selective reduction of both apoC-III and triglyceride in all preclinical pharmacological evaluations. We also showed that inhibition of apoC-III was well tolerated and not associated with increased liver triglyceride deposition or hepatotoxicity. A double-blind, placebo-controlled, phase I clinical study was performed in healthy subjects. Administration of the human apoC-III antisense drug resulted in dose-dependent reductions in plasma apoC-III, concomitant lowering of triglyceride levels, and produced no clinically meaningful signals in the safety evaluations. Antisense inhibition of apoC-III in preclinical models and in a phase I clinical trial with healthy subjects produced potent, selective reductions in plasma apoC-III and triglyceride, 2 known risk factors for cardiovascular disease. This compelling pharmacological profile supports further clinical investigations in hypertriglyceridemic subjects.

Generation and analysis of plasmas with centrally reduced helicity in full-tungsten ASDEX upgrade

Energy Technology Data Exchange (ETDEWEB)

Bock, Alexander

2016-03-01

The most promising concepts for harnessing nuclear fusion are toroidal devices like tokamaks, where a plasma is confined by helically twisted magnetic field lines. To provide the twisting of the field lines, a tokamak relies on a toroidal current in the plasma, which is largely generated by a transformer. As such, conventional tokamaks are limited to pulsed operation. Moreover, this current makes tokamak plasmas prone to numerous confinement degrading magnetohydrodynamic (MHD) instabilities that can emerge at locations where the field line helicity q takes on rational values like 1/1, 3/2 or 2/1, i.e. sawteeth or neoclassical tearing modes (NTMs). This thesis presents studies of plasmas with centrally elevated q-profiles created by external electron-cyclotron and neutral beam current drive (ECCD/NBCD) under steady-state conditions in the full-tungsten tokamak ASDEX Upgrade. Without the usually monotonic q-profile, instabilities of low helicity disappear, thereby improving the plasma stability. Furthermore, elevating q increases the amount of so-called (toroidal) bootstrap current, which the plasma drives by itself in the presence of pressure gradients, thereby reducing the reliance on the transformer. In the best case, an advanced tokamak (AT) could thus run in steady state. Additionally, an elevated and thus flat/slightly reversed q-profile is thought to improve confinement by impeding turbulent transport. Reconstruction of the tailored q-profile is accomplished with the new integrated data equilibrium (IDE) code and information from a key diagnostic that is based on the Motional Stark Effect (MSE). During the course of this work it was discovered that the MSE diagnostic suffers from interference from polarised background light. A prototype mitigation system was successfully tested. Also, non-linearities in the diagnostic's optical relay system were found and a calibration scheme devised to take them into account. Both the conventional approach of AT

Effects of differential supplementation of fatty acids during the peripartum and breeding periods of Holstein cows: I. Uterine and metabolic responses, reproduction, and lactation.

Science.gov (United States)

Silvestre, F T; Carvalho, T S M; Francisco, N; Santos, J E P; Staples, C R; Jenkins, T C; Thatcher, W W

2011-01-01

The objectives were to evaluate the effects of differential timing of supplementation of different Ca salts (CS) of fatty acids (FA) on FA profiles of cotyledonary-caruncular tissues, metabolic status, uterine health, pregnancy, pregnancy losses after 2 artificial inseminations (AI), and milk yield. Holstein cows (n=1,380) were assigned randomly to be fed either CS of palm oil (PO) or safflower oil (SO) from 30 d prepartum until 30 d postpartum (dpp) and further randomized to receive either CS of PO or fish oil (FO) from 30 to 160 dpp. Supplementation of CS of FA was at 1.5% of dietary dry matter. Tissues (n=23) and blood (n=32) were collected from a subsample of cows. Blood was collected daily from parturition to 10 dpp and three times weekly thereafter until 30 dpp for analyses of PGF2α metabolite, nonesterified FA, β-hydroxybutyric acid, blood urea nitrogen, and glucose. Cows were evaluated once between 8 to 10 dpp for cervical discharge type. At 43 dpp, cows received 2 injections of PGF2α 14 d apart, followed 14 d later by injections of GnRH at 7 d before and 56 h after an injection of PGF2α with AI at 16 h after the second GnRH injection. All cows received intravaginally a controlled internal drug-releasing device, containing 1.38 g of progesterone, at 18 d after the first AI followed 7 d later by removal of the device and injection of GnRH. Nonpregnant cows at 32 d after AI were injected with PGF2α, followed 56 h later with a GnRH injection and second AI 16 h thereafter. Cows diagnosed pregnant after both AI were re-examined at 60 d of pregnancy to determine pregnancy losses. Milk weights were recorded monthly for all cows. Caruncular n-6:n-3 FA ratio was greater in cows fed SO. Plasma concentrations of metabolites and frequency of cervical discharge type did not differ between PO- and SO-fed cows. Plasma PGF2α metabolite was greater in SO-fed cows at 4 and 7 dpp. Pregnancy per AI at 32 and 60 d post first AI was not affected by diets, but pregnancy

Bile acid sequestration reduces plasma glucose levels in db/db mice by increasing its metabolic clearance rate.

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Maxi Meissner

Full Text Available AIMS/HYPOTHESIS: Bile acid sequestrants (BAS reduce plasma glucose levels in type II diabetics and in murine models of diabetes but the mechanism herein is unknown. We hypothesized that sequestrant-induced changes in hepatic glucose metabolism would underlie reduced plasma glucose levels. Therefore, in vivo glucose metabolism was assessed in db/db mice on and off BAS using tracer methodology. METHODS: Lean and diabetic db/db mice were treated with 2% (wt/wt in diet Colesevelam HCl (BAS for 2 weeks. Parameters of in vivo glucose metabolism were assessed by infusing [U-(13C]-glucose, [2-(13C]-glycerol, [1-(2H]-galactose and paracetamol for 6 hours, followed by mass isotopologue distribution analysis, and related to metabolic parameters as well as gene expression patterns. RESULTS: Compared to lean mice, db/db mice displayed an almost 3-fold lower metabolic clearance rate of glucose (p = 0.0001, a ∼300% increased glucokinase flux (p = 0.001 and a ∼200% increased total hepatic glucose production rate (p = 0.0002. BAS treatment increased glucose metabolic clearance rate by ∼37% but had no effects on glucokinase flux nor total hepatic or endogenous glucose production. Strikingly, BAS-treated db/db mice displayed reduced long-chain acylcarnitine content in skeletal muscle (p = 0.0317 but not in liver (p = 0.189. Unexpectedly, BAS treatment increased hepatic FGF21 mRNA expression 2-fold in lean mice (p = 0.030 and 3-fold in db/db mice (p = 0.002. CONCLUSIONS/INTERPRETATION: BAS induced plasma glucose lowering in db/db mice by increasing metabolic clearance rate of glucose in peripheral tissues, which coincided with decreased skeletal muscle long-chain acylcarnitine content.

Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy. INCAS Study Group.

Science.gov (United States)

Pakker, N G; Kroon, E D; Roos, M T; Otto, S A; Hall, D; Wit, F W; Hamann, D; van der Ende, M E; Claessen, F A; Kauffmann, R H; Koopmans, P P; Kroon, F P; ten Napel, C H; Sprenger, H G; Weigel, H M; Montaner, J S; Lange, J M; Reiss, P; Schellekens, P T; Miedema, F

1999-02-04

Current antiretroviral treatment can induce significant and sustained virological and immunological responses in HIV-1-infected persons over at least the short- to mid-term. In this study, long-term immune reconstitution was investigated during highly active antiretroviral therapy. Patients enrolled in the INCAS study in The Netherlands were treated for 102 weeks (range 52-144 weeks) with nevirapine (NVP) + zidovudine (ZDV) (n = 9), didanosine (ddl) + ZDV (n = 10), or NVP + ddl + ZDV (n = 10). Memory and naïve CD4+ and CD8+ T cells were measured using CD45RA and CD27 monoclonal antibodies (mAb), T-cell function was assayed by CD3 + CD28 mAb stimulation, and plasma HIV-1 RNA load was measured by ultra-direct assay (cut-off < 20 copies/ml). Compared to both double combination regimens the triple combination regimen resulted in the most sustained increase in CD4+ T cells (change in CD4+, + 253 x 10(6) cells/l; standard error, 79 x 10(6) cells/l) and reduction of plasma HIV-1 RNA. In nine patients (31%) (ddl + ZDV, n = 2; NVP + ddl + ZDV, n = 7) plasma HIV-1 RNA levels remained below cut-off for at least 2 years. On average, these long-term virological responders demonstrated a significantly higher increase of naïve and memory CD4+ T cells (P = 0.01 and 0.02, respectively) as compared with patients with a virological failure, and showed improved T-cell function and normalization of the naïve; memory CD8+ T-cell ratio. However, individual virological success or failure did not predict the degree of immunological response. T-cell patterns were independent of baseline CD4+ T-cell count, T-cell function, HIV-1 RNA load or age. Low numbers of naïve CD4+ T cells at baseline resulted in modest long-term naïve T-cell recovery. Patients with prolonged undetectable plasma HIV-1 RNA levels during antiretroviral therapy do not invariably show immune restoration. Naïve T-cell recovery in the setting of complete viral suppression is a gradual process, similar to that reported

Synergistic activity of tenofovir and nevirapine combinations released from polycaprolactone matrices for potential enhanced prevention of HIV infection through the vaginal route.

Science.gov (United States)

Dang, Nhung T T; Sivakumaran, Haran; Harrich, David; Shaw, Paul N; Davis-Poynter, Nicholas; Coombes, Allan G A

2014-10-01

Polycaprolactone (PCL) matrices were simultaneously loaded with the antiviral agents, tenofovir (TFV) and nevirapine (NVP), in combination to provide synergistic activity in the prevention of HIV transmission through the vaginal route. TFV and NVP were incorporated in PCL matrices at theoretical loadings of 10%TFV-10% NVP, 5%TFV-5%NVP and 5%TFV-10%NVP, measured with respect to the PCL content of the matrices. Actual TFV loadings ranged from 2.1% to 4.2% equating to loading efficiencies of about 41-42%. The actual loadings of NVP were around half those of TFV (1.2-1.9%), resulting in loading efficiencies ranging from 17.2% to 23.5%. Approximately 80% of the initial content of TFV was released from the PCL matrices into simulated vaginal fluid (SVF) over a period of 30 days, which was almost double the cumulative release of NVP (40-45%). The release kinetics of both antivirals over 30 days were found to be described most satisfactorily by the Higuchi model. In vitro assay of release media containing combinations of TFV and NVP released from PCL matrices confirmed a potential synergistic/additive effect of the released antivirals on HIV-1 infection of HeLa cells. These findings indicate that PCL matrices loaded with combinations of TFV and NVP provide an effective strategy for the sustained vaginal delivery of antivirals with synergistic/additive activity. Copyright © 2014 Elsevier B.V. All rights reserved.

Effectiveness and safety of dipeptidyl peptidase 4 inhibitors in the management of type 2 diabetes in older adults: a systematic review and development of recommendations to reduce inappropriate prescribing.

Science.gov (United States)

Schott, Gisela; Martinez, Yolanda V; Ediriweera de Silva, R Erandie; Renom-Guiteras, Anna; Vögele, Anna; Reeves, David; Kunnamo, Ilkka; Marttila-Vaara, Minna; Sönnichsen, Andreas

2017-10-16

Preventable drug-related hospital admissions can be associated with drugs used in diabetes and the benefits of strict diabetes control may not outweigh the risks, especially in older populations. The aim of this study was to look for evidence on risks and benefits of DPP-4 inhibitors in older adults and to use this evidence to develop recommendations for the electronic decision support tool of the PRIMA-eDS project. Systematic review using a staged approach which searches for systematic reviews and meta-analyses first, then individual studies only if prior searches were inconclusive. The target population were older people (≥65 years old) with type 2 diabetes. We included studies reporting on the efficacy and/or safety of DPP-4 inhibitors for the management of type 2 diabetes. Studies were included irrespective of DPP-4 inhibitors prescribed as monotherapy or in combination with any other drug for the treatment of type 2 diabetes. The target intervention was DPP-4 inhibitors compared to placebo, no treatment, other drugs to treat type 2 diabetes or a non-pharmacological intervention. Thirty studies (reported in 33 publications) were included: 1 meta-analysis, 17 intervention studies and 12 observational studies. Sixteen studies were focused on older adults and 14 studies reported subgroup analyses in participants ≥65, ≥70, or ≥75 years. Comorbidities were reported by 26 studies and frailty or functional status by one study. There were conflicting findings regarding the effectiveness of DPP-4 inhibitors in older adults. In general, DPP-4 inhibitors showed similar or better safety than placebo and other antidiabetic drugs. However, these safety data are mainly based on short-term outcomes like hypoglycaemia in studies with HbA1c control levels recommended for younger people. One recommendation was developed advising clinicians to reconsider the use of DPP-4 inhibitors for the management of type 2 diabetes in older adults with HbA1c companies and authored or

Reduced plasma adiponectin concentrations may contribute to impaired insulin activation of glycogen synthase in skeletal muscle of patients with type 2 diabetes

DEFF Research Database (Denmark)

Højlund, K.; Frystyk, J.; Levin, K.

2006-01-01

AIMS/HYPOTHESIS: Circulating levels of adiponectin are negatively associated with multiple indices of insulin resistance, and the concentration is reduced in humans with insulin resistance and type 2 diabetes. However, the mechanisms by which adiponectin improves insulin sensitivity remain unclear...... (ten lean, 21 obese and 20 with type 2 diabetes). RESULTS: Plasma adiponectin was significantly reduced in type 2 diabetic compared with obese and lean subjects. In lean and obese subjects, insulin significantly reduced plasma adiponectin, but this response was blunted in patients with type 2 diabetes...... by improving the capacity to switch from lipid to glucose oxidation and to store glucose as glycogen in response to insulin, and that low adiponectin may contribute to impaired insulin activation of GS in skeletal muscle of patients with type 2 diabetes....

Vitamin C Deficiency Reduces Muscarinic Receptor Coronary Artery Vasoconstriction and Plasma Tetrahydrobiopterin Concentration in Guinea Pigs

Directory of Open Access Journals (Sweden)

Gry Freja Skovsted

2017-07-01

Full Text Available Vitamin C (vitC deficiency is associated with increased cardiovascular disease risk, but its specific interplay with arteriolar function is unclear. This study investigates the effect of vitC deficiency in guinea pigs on plasma biopterin status and the vasomotor responses in coronary arteries exposed to vasoconstrictor/-dilator agents. Dunkin Hartley female guinea pigs (n = 32 were randomized to high (1500 mg/kg diet or low (0 to 50 mg/kg diet vitC for 10–12 weeks. At euthanasia, coronary artery segments were dissected and mounted in a wire-myograph. Vasomotor responses to potassium, carbachol, sodium nitroprusside (SNP, U46619, sarafotoxin 6c (S6c and endothelin-1 (ET-1 were recorded. Plasma vitC and tetrahydrobiopterin were measured by HPLC. Plasma vitC status reflected the diets with deficient animals displaying reduced tetrahydrobiopterin. Vasoconstrictor responses to carbachol were significantly decreased in vitC deficient coronary arteries independent of their general vasoconstrictor/vasodilator capacity (p < 0.001. Moreover, in vitC deficient animals, carbachol-induced vasodilator responses correlated with coronary artery diameter (p < 0.001. Inhibition of cyclooxygenases with indomethacin increased carbachol-induced vasoconstriction, suggesting an augmented carbachol-induced release of vasodilator prostanoids. Atropine abolished carbachol-induced vasomotion, supporting a specific muscarinic receptor effect. Arterial responses to SNP, potassium, S6c, U46619 and ET-1 were unaffected by vitC status. The study shows that vitC deficiency decreases tetrahydrobiopterin concentrations and muscarinic receptor mediated contraction in coronary arteries. This attenuated vasoconstrictor response may be linked to altered production of vasoactive arachidonic acid metabolites and reduced muscarinic receptor expression/signaling.

Reducing wall plasma expansion with gold foam irradiated by laser

International Nuclear Information System (INIS)

Zhang, Lu; Ding, Yongkun; Jiang, Shaoen; Yang, Jiamin; Li, Hang; Kuang, Longyu; Lin, Zhiwei; Jing, Longfei; Li, Liling; Deng, Bo; Yuan, Zheng; Chen, Tao; Yuan, Guanghui; Tan, Xiulan; Li, Ping

2015-01-01

The experimental study on the expanding plasma movement of low-density gold foam (∼1% solid density) irradiated by a high power laser is reported in this paper. Experiments were conducted using the SG-III prototype laser. Compared to solid gold with 19.3 g/cc density, the velocities of X-ray emission fronts moving off the wall are much smaller for gold foam with 0.3 g/cc density. Theoretical analysis and MULTI 1D simulation results also show less plasma blow-off, and that the density contour movement velocities of gold foam are smaller than those of solid gold, agreeing with experimental results. These results indicate that foam walls have advantages in symmetry control and lowering plasma fill when used in ignition hohlraum

Reducing wall plasma expansion with gold foam irradiated by laser

Energy Technology Data Exchange (ETDEWEB)

Zhang, Lu; Ding, Yongkun, E-mail: ding-yk@vip.sina.com; Jiang, Shaoen, E-mail: jiangshn@vip.sina.com; Yang, Jiamin; Li, Hang; Kuang, Longyu; Lin, Zhiwei; Jing, Longfei; Li, Liling; Deng, Bo; Yuan, Zheng; Chen, Tao; Yuan, Guanghui; Tan, Xiulan; Li, Ping [Research Center of Laser Fusion, China Academy of Engineering Physics, P.O. Box 919-986, Mianyang 621900 (China)

2015-11-15

The experimental study on the expanding plasma movement of low-density gold foam (∼1% solid density) irradiated by a high power laser is reported in this paper. Experiments were conducted using the SG-III prototype laser. Compared to solid gold with 19.3 g/cc density, the velocities of X-ray emission fronts moving off the wall are much smaller for gold foam with 0.3 g/cc density. Theoretical analysis and MULTI 1D simulation results also show less plasma blow-off, and that the density contour movement velocities of gold foam are smaller than those of solid gold, agreeing with experimental results. These results indicate that foam walls have advantages in symmetry control and lowering plasma fill when used in ignition hohlraum.

The metabolite generated by dipeptidyl-peptidase 4 metabolism of glucagon-like peptide-1 has no influence on plasma glucose levels in patients with type 2 diabetes

DEFF Research Database (Denmark)

Zander, M; Madsbad, S; Deacon, C F

2006-01-01

AIM/HYPOTHESIS: Glucagon-like peptide-1 (GLP-1) is metabolised by the enzyme dipeptidyl-peptidase 4 (DPP-4), generating a metabolite with potential antagonistic properties. This study was conducted to evaluate the effect of that metabolite on plasma glucose levels in patients with type 2 diabetes...... of the metabolite increased from 1+/-3 (SAL) and 2+/-6 (IB) pmol/l to 42+/-4 (LSC), 64+/-8 (IV) and 327+/-16 (HSC) pmol/l, pglucose levels at 6 h decreased from 12.4+/-1.1 (SAL) mmol/l to 10.4+/-1.1 (LSC), 8.6+/-0.6 (IB), 8.8+/-0.8 (IV) and 9.1+/-0.9 (HSC) mmol/l, p.../INTERPRETATION: At approximately similar concentrations of intact GLP-1 (IV, IB, HSC), but with widely ranging metabolite concentrations, the effect on plasma glucose levels was equal, indicating that the presence of the metabolite does not antagonise the glucose-lowering effect of GLP-1....

The efficacy, pharmacokinetics, safety and cardiovascular risks of switching nevirapine to rilpivirine in HIV-1 patients: the RPV switch study

NARCIS (Netherlands)

Rokx, C.; Blonk, M.; Verbon, A.; Burger, D.M.; Rijnders, B.J.

2014-01-01

INTRODUCTION: Nevirapine (NVP) induces cytochrome P450 3A4 by which rilpivirine (RPV) is metabolized. Switching NVP to RPV could result in decreased RPV exposure with subsequent virological failure and dyslipidemia because NVP is regarded as the least dyslipidemic, non-nucleoside, reverse

Acetyl CoA Carboxylase Inhibition Reduces Hepatic Steatosis but Elevates Plasma Triglycerides in Mice and Humans: A Bedside to Bench Investigation.

Science.gov (United States)

Kim, Chai-Wan; Addy, Carol; Kusunoki, Jun; Anderson, Norma N; Deja, Stanislaw; Fu, Xiaorong; Burgess, Shawn C; Li, Cai; Ruddy, Marcie; Chakravarthy, Manu; Previs, Steve; Milstein, Stuart; Fitzgerald, Kevin; Kelley, David E; Horton, Jay D

2017-08-01

Inhibiting lipogenesis prevents hepatic steatosis in rodents with insulin resistance. To determine if reducing lipogenesis functions similarly in humans, we developed MK-4074, a liver-specific inhibitor of acetyl-CoA carboxylase (ACC1) and (ACC2), enzymes that produce malonyl-CoA for fatty acid synthesis. MK-4074 administered to subjects with hepatic steatosis for 1 month lowered lipogenesis, increased ketones, and reduced liver triglycerides by 36%. Unexpectedly, MK-4074 increased plasma triglycerides by 200%. To further investigate, mice that lack ACC1 and ACC2 in hepatocytes (ACC dLKO) were generated. Deletion of ACCs decreased polyunsaturated fatty acid (PUFA) concentrations in liver due to reduced malonyl-CoA, which is required for elongation of essential fatty acids. PUFA deficiency induced SREBP-1c, which increased GPAT1 expression and VLDL secretion. PUFA supplementation or siRNA-mediated knockdown of GPAT1 normalized plasma triglycerides. Thus, inhibiting lipogenesis in humans reduced hepatic steatosis, but inhibiting ACC resulted in hypertriglyceridemia due to activation of SREBP-1c and increased VLDL secretion. Copyright © 2017 Elsevier Inc. All rights reserved.

Clovamide-rich extract from Trifolium pallidum reduces oxidative stress-induced damage to blood platelets and plasma.

Science.gov (United States)

Kolodziejczyk, Joanna; Olas, Beata; Wachowicz, Barbara; Szajwaj, Barbara; Stochmal, Anna; Oleszek, Wieslaw

2011-09-01

Numerous plants (including clovers) have been widely used in folk medicine for the treatment of different disorders. This in vitro study was designed to examine the antioxidative effects of the clovamide-rich fraction, obtained from aerial parts of Trifolium pallidum, in the protection of blood platelets and plasma against the nitrative and oxidative damage, caused by peroxynitrite (ONOO(-)). Carbonyl groups and 3-nitrotyrosine in blood platelet and plasma proteins were determined by ELISA tests. Thiol groups level was estimated by using 5,5'-dithio-bis(2-nitro-benzoic acid, DTNB). Plasma lipid peroxidation was measured spectrophotometrically as the production of thiobarbituric acid reactive substances. The results from our work indicate that clovamide-rich T. pallidum extract may reveal the protective properties in the prevention against oxidative stress. The presence of clovamide-rich T. pallidum extract (12.5-100 μg/ml) partly inhibited ONOO(-)-mediated protein carbonylation and nitration. All the used concentrations of T. pallidum extract reduced lipid peroxidation in plasma. The antioxidative action of the tested extract in the protection of blood platelet lipids was less effective; the extract at the lowest final concentration (12.5 μg/ml) had no protective effect against lipid peroxidation. The present results indicate that the extract from T. pallidum is likely to be a source of compounds with the antioxidative properties, useful in the prevention against the oxidative stress-related diseases.

Newer polyanionic bio-composite anode for sodium ion batteries

Science.gov (United States)

Karuppiah, Saravanan; Vellingiri, Suganya; Nallathamby, Kalaiselvi

2017-02-01

NASICON frame work Na3V2(PO4)3 (NVP), wrapped by nitrogen and sulfur doped bio-carbon matrix derived from human hair (HHC) has been investigated for its anode behavior in SIBs. Basically, NVP is bestowed with a crystal structure of 3D open framework and a moderate theoretical capacity of 118 mAh g-1, which are the twin advantages and motivation behind the selection of this material. Prepared through a simple, scalable and facile method, the key problems associated with pristine NVP electrode material, such as inferior conductivity and severe volume change have been mitigated to a great extent through the formation of a composite containing HHC. Herein, HHC is a cheap and eco-friendly composite additive, obtained from a universal bio-waste, viz., human hair and hence NVP/HHC qualifies itself as a green composite. Interestingly, NVP/HHC-10 (in-situ) and NVP/HHC-20 (ex-situ) anodes show excellent electrochemical performance in terms of cycling stability up to 500 cycles and rate capability @ 2 A g-1, which are superior than similar category NVP anodes reported in the literature. Further, post cycling structure and morphology of NVP/HHC composite anodes evidence the appreciable stability bestowed with the select composition, which is found to get maintained upon extended cycles and even after rate capability test.

The calculation of turbulence phenomena in plasma focus dynamics using REDUCE

International Nuclear Information System (INIS)

Hayd, A.; Maurer, M.; Meinke, P.; Kaeppeler, H.J.

1982-05-01

Based on previous calculations of the development of highly turbulent plasma states resulting from m=0 instabilities and the application to the turbulent development in the late stage of a plasma focus experiment, using REDUE, the treatment of plasma focus dynamics is extended to the compression stage and 'intermediate' stage between maximum density and m = o onset. For this, a two-fluid model of the magneto-fluid dynamic equations is employed. The non-linear development is again treated in ω, k-space and transformed back into r, t-space to obtain local dynamic variables as functions of time. The calculation is applied to the Stuttgart plasma focus experiment POSEIDON. It is shown that for relatively high pinch currents, neutron production also appears in the 'intermediate' phase, the life-time of which increases with increasing pinch current. (orig.)

Mirror plasma apparatus

International Nuclear Information System (INIS)

Moir, R.W.

1981-01-01

A mirror plasma apparatus which utilizes shielding by arc discharge to form a blanket plasma and lithium walls to reduce neutron damage to the wall of the apparatus. An embodiment involves a rotating liquid lithium blanket for a tandem mirror plasma apparatus wherein the first wall of the central mirror cell is made of liquid lithium which is spun with angular velocity great enough to keep the liquid lithium against the first material wall, a blanket plasma preventing the lithium vapor from contaminating the plasma

In-home HIV testing and nevirapine dosing by traditional birth attendants in rural Zambia: a feasibility study.

Science.gov (United States)

Brennan, Alana T; Thea, Donald M; Semrau, Katherine; Goggin, Caitlin; Scott, Nancy; Pilingana, Portipher; Botha, Belinda; Mazimba, Arthur; Hamomba, Leoda; Seidenberg, Phil

2014-01-01

Access to lifesaving prevention of mother-to-child transmission (PMTCT) services is problematic in rural Zambia. The simplest intervention used in Zambia has been 2-dose nevirapine (NVP) administration in the peripartum period, a regimen of 1 NVP tablet to the mother at the onset of labor and 1 dose in the form of syrup to the newborn within 4 to 72 hours after birth. This 2-dose regimen has been shown to reduce MTCT by nearly 50%. We set out to demonstrate that in-home HIV testing and NVP dosing by traditional birth attendants (TBAs) is feasible and acceptable by women in rural Zambia. This was a pilot program using TBAs to perform rapid saliva-based HIV testing and administer single-dose NVP in tablet form to the mother at the onset of labor and syrup to the infant after birth. A total of 280 pregnant women were consented and enrolled into the program, of whom 124 (44.3%) gave birth at home with the assistance of a trained TBA. Of those, 16 (12.9%) were known to be HIV positive, and 101 of the remaining 108 (93.5%) accepted a rapid HIV test. All these women tested HIV negative. In the subset of 16 mothers who were HIV positive, 13 (81.3%) took single-dose NVP administered by a TBA between 1 and 24 hours prior to birth and 100% of exposed newborns (16 of 16) received NVP syrup within 72 hours after birth, 80% of whom were dosed in the first 24 hours of life. With the substantial shortage of human resources in public health care throughout sub-Saharan Africa, it is extremely valuable to utilize lay health care workers to help extended services beyond the level of the facility. Given the high uptake of PMTCT services we believe that TBAs with proper training and support can successfully provide country-approved PMTCT. © 2013 by the American College of Nurse-Midwives.

Sustained Dorzolamide Release Prevents Axonal and Retinal Ganglion Cell Loss in a Rat Model of IOP-Glaucoma.

Science.gov (United States)

Pitha, Ian; Kimball, Elizabeth C; Oglesby, Ericka N; Pease, Mary Ellen; Fu, Jie; Schaub, Julie; Kim, Yoo-Chun; Hu, Qi; Hanes, Justin; Quigley, Harry A

2018-04-01

To determine if one injection of a sustained release formulation of dorzolamide in biodegradable microparticles (DPP) reduces retinal ganglion cell (RGC) loss in a rat model of glaucoma. We injected either DPP or control microparticles intravitreally in rats. Two days later, unilateral ocular hypertension was induced by translimbal, diode laser treatment by a surgeon masked to treatment group. IOP and clinical exams were performed until sacrifice 6 weeks after laser treatment. RGC loss was measured by masked observers in both optic nerve cross-sections and RGC layer counts from retinal whole mounts. Cumulative IOP exposure was significantly reduced by DPP injection (49 ± 48 mm Hg × days in treated versus 227 ± 191 mm Hg × days in control microparticle eyes; P = 0.012, t -test). While control-injected eyes increased in axial length by 2.4 ± 1.7%, DPP eyes did not significantly enlarge (0.3 ± 2.2%, difference from control, P = 0.03, t -test). RGC loss was significantly less in DPP eyes compared with control microparticle injection alone (RGC axon count reduction: 21% vs. 52%; RGC body reduction: 25% vs. 50% [beta tubulin labeling]; P = 0.02, t -test). A single injection of sustained release DPP protected against RGC loss and axial elongation in a rat model of IOP glaucoma. Sustained release IOP-lowering medications have the potential to stop glaucoma progression.

Medical Care Expenditures for Individuals with Prediabetes: The Potential Cost Savings in Reducing the Risk of Developing Diabetes.

Science.gov (United States)

Khan, Tamkeen; Tsipas, Stavros; Wozniak, Gregory

2017-10-01

The United States has 86 million adults with prediabetes. Individuals with prediabetes can prevent or delay the development of type 2 diabetes through lifestyle modifications such as participation in the National Diabetes Prevention Program (DPP), thereby mitigating the medical and economic burdens associated with diabetes. A cohort analysis of a commercially insured population was conducted using individual-level claims data from Truven Health MarketScan ® Lab Database to identify adults with prediabetes, track whether they develop diabetes, and compare medical expenditures for those who are newly diagnosed with diabetes to those who are not. This study then illustrates how reducing the risk of developing diabetes by participation in an evidence-based lifestyle change program could yield both positive net savings on medical care expenditures and return on investment (ROI). Annual expenditures are found to be nearly one third higher for those who develop diabetes in subsequent years relative to those who do not transition from prediabetes to diabetes, with an average difference of $2671 per year. At that cost differential, the 3-year ROI for a National DPP is estimated to be as high as 42%. The results show the importance and economic benefits of participation in lifestyle intervention programs to prevent or delay the onset of type 2 diabetes.

Possible hepatotoxic consequence of nevirapine use in juvenile albino rats

Directory of Open Access Journals (Sweden)

Elias Adikwu

2017-08-01

Full Text Available Context: Nevirapine (NVP is used in human immunodeficiency virus exposed neonates. This could present safety concern due to decreased liver metabolizing enzymes activity and renal clearance in neonates. Aims: To determine the hepatotoxic effect of NVP in juvenile albino rats. Methods: Juvenile albino rats were weighed, divided into groups and treated orally with 4-32 mg/kg/day of NVP for 14 days including a recovery group. The control groups were treated with water (placebo and normal saline (solvent. At the end of NVP treatment, rats were weighed and sacrificed, blood was collected and serum extracted. Serum was analyzed for alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP, total bilirubin (TB and conjugated bilirubin (CB. The liver was harvested via dissection, weighed and evaluated for AST, ALT, ALP, superoxide dismutase (SOD, catalase (CAT, glutathione (GSH, malondialdehyde (MDA levels and histological damage. Results: The body, absolute and relative liver weights of rats in NVP treated groups were not significantly different (p>0.05 when compared to placebo. However, serum levels of AST, ALT, ALP, TB and CB were significantly increased (p<0.05 in a dose-dependent manner in NVP-treated groups. Furthermore, liver levels of ALT, ALP, AST and MDA were significantly increased (p<0.05 while SOD, CAT, and GSH were decreased in a dose dependent manner in NVP-treated groups. NVP-treated rats were characterized by varying degrees of hepatic morphological alterations. However, in the recovery group, the effects of NVP were reversed. Conclusions: This study observed dose-dependent and reversible hepatotoxicity in nevirapine- treated juvenile albino rats.

Spectral survey of helium lines in a linear plasma device for use in HELIOS imaging

Energy Technology Data Exchange (ETDEWEB)

Ray, H. B., E-mail: rayhb@ornl.gov [University of Tennessee, Knoxville, Tennessee 37996 (United States); Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831 (United States); Biewer, T. M.; Fehling, D. T.; Isler, R. C.; Unterberg, E. A. [Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831 (United States)

2016-11-15

Fast visible cameras and a filterscope are used to examine the visible light emission from Oak Ridge National Laboratory’s Proto-MPEX. The filterscope has been configured to perform helium line ratio measurements using emission lines at 667.9, 728.1, and 706.5 nm. The measured lines should be mathematically inverted and the ratios compared to a collisional radiative model (CRM) to determine T{sub e} and n{sub e}. Increasing the number of measurement chords through the plasma improves the inversion calculation and subsequent T{sub e} and n{sub e} localization. For the filterscope, one spatial chord measurement requires three photomultiplier tubes (PMTs) connected to pellicle beam splitters. Multiple, fast visible cameras with narrowband filters are an alternate technique for performing these measurements with superior spatial resolution. Each camera contains millions of pixels; each pixel is analogous to one filterscope PMT. The data can then be inverted and the ratios compared to the CRM to determine 2-dimensional “images” of T{sub e} and n{sub e} in the plasma. An assessment is made in this paper of the candidate He I emission lines for an imaging technique.

Comparative Observation of Ar, Ar-H2 and Ar-N2 DC Arc Plasma Jets and Their Arc Root Behaviour at Reduced Pressure

International Nuclear Information System (INIS)

Pan Wenxia; Meng Xian; Li Teng; Chen Xi; Wu Chengkang

2007-01-01

Results observed experimentally are presented, about the DC arc plasma jets and their arc-root behaviour generated at reduced gas pressure without or with an applied magnetic field. Pure argon, argon-hydrogen or argon-nitrogen mixture was used as the plasma-forming gas. A specially designed copper mirror was used for a better observation of the arc-root behaviour on the anode surface of the DC non-transferred arc plasma torch. It was found that in the cases without an applied magnetic field, the laminar plasma jets were stable and approximately axisymmetrical. The arc-root attachment on the anode surface was completely diffusive when argon was used as the plasma-forming gas, while the arc-root attachment often became constrictive when hydrogen or nitrogen was added into the argon. As an external magnetic field was applied, the arc root tended to rotate along the anode surface of the non-transferred arc plasma torch

Seed disinfection effect of atmospheric pressure plasma and low pressure plasma on Rhizoctonia solani.

Science.gov (United States)

Nishioka, Terumi; Takai, Yuichiro; Kawaradani, Mitsuo; Okada, Kiyotsugu; Tanimoto, Hideo; Misawa, Tatsuya; Kusakari, Shinichi

2014-01-01

Gas plasma generated and applied under two different systems, atmospheric pressure plasma and low pressure plasma, was used to investigate the inactivation efficacy on the seedborne pathogenic fungus, Rhizoctonia solani, which had been artificially introduced to brassicaceous seeds. Treatment with atmospheric plasma for 10 min markedly reduced the R. solani survival rate from 100% to 3% but delayed seed germination. The low pressure plasma treatment reduced the fungal survival rate from 83% to 1.7% after 10 min and the inactivation effect was dependent on the treatment time. The seed germination rate after treatment with the low pressure plasma was not significantly different from that of untreated seeds. The air temperature around the seeds in the low pressure system was lower than that of the atmospheric system. These results suggested that gas plasma treatment under low pressure could be effective in disinfecting the seeds without damaging them.

Reduced plasma aldosterone concentrations in randomly selected patients with insulin-dependent diabetes mellitus.

LENUS (Irish Health Repository)

Cronin, C C

2012-02-03

Abnormalities of the renin-angiotensin system have been reported in patients with diabetes mellitus and with diabetic complications. In this study, plasma concentrations of prorenin, renin, and aldosterone were measured in a stratified random sample of 110 insulin-dependent (Type 1) diabetic patients attending our outpatient clinic. Fifty-four age- and sex-matched control subjects were also examined. Plasma prorenin concentration was higher in patients without complications than in control subjects when upright (geometric mean (95% confidence intervals (CI): 75.9 (55.0-105.6) vs 45.1 (31.6-64.3) mU I-1, p < 0.05). There was no difference in plasma prorenin concentration between patients without and with microalbuminuria and between patients without and with background retinopathy. Plasma renin concentration, both when supine and upright, was similar in control subjects, in patients without complications, and in patients with varying degrees of diabetic microangiopathy. Plasma aldosterone was suppressed in patients without complications in comparison to control subjects (74 (58-95) vs 167 (140-199) ng I-1, p < 0.001) and was also suppressed in patients with microvascular disease. Plasma potassium was significantly higher in patients than in control subjects (mean +\\/- standard deviation: 4.10 +\\/- 0.36 vs 3.89 +\\/- 0.26 mmol I-1; p < 0.001) and plasma sodium was significantly lower (138 +\\/- 4 vs 140 +\\/- 2 mmol I-1; p < 0.001). We conclude that plasma prorenin is not a useful early marker for diabetic microvascular disease. Despite apparently normal plasma renin concentrations, plasma aldosterone is suppressed in insulin-dependent diabetic patients.

Particle modeling of plasmas computational plasma physics

International Nuclear Information System (INIS)

Dawson, J.M.

1991-01-01

Recently, through the development of supercomputers, a powerful new method for exploring plasmas has emerged; it is computer modeling of plasmas. Such modeling can duplicate many of the complex processes that go on in a plasma and allow scientists to understand what the important processes are. It helps scientists gain an intuition about this complex state of matter. It allows scientists and engineers to explore new ideas on how to use plasma before building costly experiments; it allows them to determine if they are on the right track. It can duplicate the operation of devices and thus reduce the need to build complex and expensive devices for research and development. This is an exciting new endeavor that is in its infancy, but which can play an important role in the scientific and technological competitiveness of the US. There are a wide range of plasma models that are in use. There are particle models, fluid models, hybrid particle fluid models. These can come in many forms, such as explicit models, implicit models, reduced dimensional models, electrostatic models, magnetostatic models, electromagnetic models, and almost an endless variety of other models. Here the author will only discuss particle models. He will give a few examples of the use of such models; these will be taken from work done by the Plasma Modeling Group at UCLA because he is most familiar with work. However, it only gives a small view of the wide range of work being done around the US, or for that matter around the world

Plasma lysophosphatidylcholine levels are reduced in obesity and type 2 diabetes.

Directory of Open Access Journals (Sweden)

Melissa N Barber

Full Text Available BACKGROUND: Obesity and type 2 diabetes (T2DM are associated with increased circulating free fatty acids and triacylglycerols. However, very little is known about specific molecular lipid species associated with these diseases. In order to gain further insight into this, we performed plasma lipidomic analysis in a rodent model of obesity and insulin resistance as well as in lean, obese and obese individuals with T2DM. METHODOLOGY/PRINCIPAL FINDINGS: Lipidomic analysis using liquid chromatography coupled to mass spectrometry revealed marked changes in the plasma of 12 week high fat fed mice. Although a number of triacylglycerol and diacylglycerol species were elevated along with of a number of sphingolipids, a particularly interesting finding was the high fat diet (HFD-induced reduction in lysophosphatidylcholine (LPC levels. As liver, skeletal muscle and adipose tissue play an important role in metabolism, we next determined whether the HFD altered LPCs in these tissues. In contrast to our findings in plasma, only very modest changes in tissue LPCs were noted. To determine when the change in plasma LPCs occurred in response to the HFD, mice were studied after 1, 3 and 6 weeks of HFD. The HFD caused rapid alterations in plasma LPCs with most changes occurring within the first week. Consistent with our rodent model, data from our small human cohort showed a reduction in a number of LPC species in obese and obese individuals with T2DM. Interestingly, no differences were found between the obese otherwise healthy individuals and the obese T2DM patients. CONCLUSION: Irrespective of species, our lipidomic profiling revealed a generalized decrease in circulating LPC species in states of obesity. Moreover, our data indicate that diet and adiposity, rather than insulin resistance or diabetes per se, play an important role in altering the plasma LPC profile.

Insecticide-treated bed nets reduce plasma antibody levels and limit the repertoire of antibodies to Plasmodium falciparum variant surface antigens

DEFF Research Database (Denmark)

Askjaer, N; Maxwell, C; Chambo, W

2001-01-01

The use of insecticide-treated bed nets (ITN) has been documented to reduce malaria morbidity and mortality in areas with endemic malaria, but concerns have been raised that ITN usage could affect the acquisition of malaria immunity. Several lines of evidence have indicated that antibodies against...... variant surface antigens (VSA) are important in the development of naturally acquired immunity to Plasmodium falciparum malaria and may thus be good indicators of immune status. We have compared the levels of VSA antibodies in plasma from children who have used ITN for 4 years to levels in plasma from...

Kr II laser-induced fluorescence for measuring plasma acceleration.

Science.gov (United States)

Hargus, W A; Azarnia, G M; Nakles, M R

2012-10-01

We present the application of laser-induced fluorescence of singly ionized krypton as a diagnostic technique for quantifying the electrostatic acceleration within the discharge of a laboratory cross-field plasma accelerator also known as a Hall effect thruster, which has heritage as spacecraft propulsion. The 728.98 nm Kr II transition from the metastable 5d(4)D(7/2) to the 5p(4)P(5/2)(∘) state was used for the measurement of laser-induced fluorescence within the plasma discharge. From these measurements, it is possible to measure velocity as krypton ions are accelerated from near rest to approximately 21 km/s (190 eV). Ion temperature and the ion velocity distributions may also be extracted from the fluorescence data since available hyperfine splitting data allow for the Kr II 5d(4)D(7/2)-5p(4)P(5/2)(∘) transition lineshape to be modeled. From the analysis, the fluorescence lineshape appears to be a reasonable estimate for the relatively broad ion velocity distributions. However, due to an apparent overlap of the ion creation and acceleration regions within the discharge, the distributed velocity distributions increase ion temperature determination uncertainty significantly. Using the most probable ion velocity as a representative, or characteristic, measure of the ion acceleration, overall propellant energy deposition, and effective electric fields may be calculated. With this diagnostic technique, it is possible to nonintrusively characterize the ion acceleration both within the discharge and in the plume.

Preoperative administration of polysaccharide Kureha and reduced plasma transforming growth factor-β in patients with advanced gastric cancer: A randomized clinical trial

Science.gov (United States)

YAMASHITA, KEISHI; SAKURAMOTO, SHINICHI; MIENO, HIROAKI; NEMOTO, MASAYUKI; SHIBATA, TOMOTAKA; KATADA, NATSUYA; OHTSUKI, SHIGEAKI; SAKAMOTO, YASUTOSHI; HOSHI, KEIKA; WANG, GUOQIN; HEMMI, OSAMU; SATOH, TOSHIHIKO; KIKUCHI, SHIRO; WATANABE, MASAHIKO

2015-01-01

Systemic abrogation of TGF-β signaling results in tumor reduction through cytotoxic T lymphocytes activity in a mouse model. The administration of polysaccharide-Kureha (PSK) into tumor-bearing mice also showed tumor regression with reduced TGF-β. However, there have been no studies regarding the PSK administration to cancer patients and the association with plasma TGF-β. PSK (3 g/day) was administered as a neoadjuvant therapy for 2 weeks before surgery. In total, 31 advanced gastric cancer (AGC) patients were randomly assigned to group A (no neoadjuvant PSK; n=14) or B (neoadjuvant PSK therapy; n=17). Plasma TGF-β was measured pre- and postoperatively. The allocation factors were clinical stage (cStage) and gender. Plasma TGF-β ranged from 1.85–43.5 ng/ml (average, 9.50 ng/ml) in AGC, and 12 patients (38.7%) had a high value, >7.0 ng/ml. These patients were largely composed of poorly-differentiated adenocarcinoma with pathological stage III/IV. All the six elevated cases in group B showed a significant reduction of plasma TGF-β (from 21.6 to 4.5 ng/ml, on average), whereas this was not exhibited in group A. The cases within the normal limits of TGF-β remained unchanged irrespective of PSK treatment. Analysis of variance showed a statistically significant reduction in the difference of plasma TGF-β between groups A and B (P=0.019). PSK reduced the plasma TGF-β in AGC patients when the levels were initially high. The clinical advantage of PSK may, however, be restricted to specific histological types of AGC. Perioperative suppression of TGF-β by PSK may antagonize cancer immune evasion and improve patient prognosis in cases of AGC. PMID:26137253

Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum.

Science.gov (United States)

Ellis, Giovanina M; Huang, Sharon; Hitti, Jane; Frenkel, Lisa M

2011-11-01

Compare the risk of HIV drug resistance in women stopping suppressive nelfinavir (NFV)-based or Nevirapine (NVP)-based antiretroviral therapy (ART) after pregnancy. Specimens collected after stopping ART were tested for drug resistance by an oligonucleotide ligation assay and consensus sequencing. When postpartum drug resistance was detected, specimens obtained at study entry and during ART were evaluated. Sixteen of 38 women with ART-induced suppression of viral replication suspended ART postpartum. Resistance mutations were detected in 75% who stopped NFV-ART and in 50% who stopped NVP-ART. M184V, associated with Lamivudine resistance, was more frequent among those randomized to NFV-ART compared with NVP-ART (6 of 8 versus 1 of 8; P = 0.04), and nonnucleoside reverse transcriptase inhibitor resistance was detected in 4 of 8 stopping NVP-ART. HIV drug resistance was frequently observed among women who stopped suppressive NVP-ART or NFV-ART postpartum. This suggests that NFV-ART may have suboptimal potency, that staggering discontinuation of NVP-ART may be warranted, and/or ART adherence may be lax in women who choose to stop ART postpartum.

The role of magnetic energy on plasma localization during the glow discharge under reduced pressure

Directory of Open Access Journals (Sweden)

Chodun Rafal

2016-06-01

Full Text Available In this work, we present the first results of our research on the synergy of fields, electric and magnetic, in the initiation and development of glow discharge under reduced pressure. In the two-electrode system under reduced pressure, the breakdown voltage characterizes a minimum energy input of the electric field to initiate and sustain the glow discharge. The glow discharge enhanced by the magnetic field applied just above the surface of the cathode influences the breakdown voltage decreasing its value. The idea of the experiment was to verify whether the contribution of potential energy of the magnetic field applied around the cathode is sufficiently effective to locate the plasma of glow discharge to the grounded cathode, which, in fact, is the part of a vacuum chamber wall (the anode is positively biased in this case. In our studies, we used the grounded magnetron unit with positively biased anode in order to achieve favorable conditions for the deposition of thin films on fibrous substrates such as fabrics for metallization, assuming that locally applied magnetic field can effectively locate plasma. The results of our studies (Paschen curve with the participation of the magnetic field seem to confirm the validity of the research assumption. What is the most spectacular - the glow discharge was initiated between introduced into the chamber anode and the grounded cathode of magnetron ‘assisted’ by the magnetic field (discharge did not include the area of the anode, which is a part of the magnetron construction.

Bactericidal active ingredient in cryopreserved plasma-treated water with the reduced-pH method for plasma disinfection

Science.gov (United States)

Kitano, Katsuhisa; Ikawa, Satoshi; Nakashima, Yoichi; Tani, Atsushi; Yokoyama, Takashi; Ohshima, Tomoko

2016-09-01

For the plasma disinfection of human body, plasma sterilization in liquid is crucial. We found that the plasma-treated water (PTW) has strong bactericidal activity under low pH condition. Physicochemical properties of PTW is discussed based on chemical kinetics. Lower temperature brings longer half-life and the bactericidal activity of PTW can be kept by cryopreservation. High performance PTW, corresponding to the disinfection power of 22 log reduction (B. subtilis spore), can be obtained by special plasma system equipped with cooling device. This is equivalent to 65% H2O2, 14% sodium hypochlorite and 0.33% peracetic acid, which are deadly poison for human. But, it is deactivated soon at higher temperature (4 sec. at body temperature), and toxicity to human body seems low. For dental application, PTW was effective on infected models of human extracted tooth. Although PTW has many chemical components, respective chemical components in PTW were isolated by ion chromatography. In addition to peaks of H2O2, NO2- and NO3-, a specific peak was detected. and only this fraction had bactericidal activity. Purified active ingredient of PTW is the precursor of HOO, and further details will be discussed in the presentation. MEXT (15H03583, 23340176, 25108505). NCCE (23-A-15).

Dipeptidyl peptidase IV in two human glioma cell lines

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A Sedo

2009-12-01

Full Text Available There is growing evidence that dipeptidyl peptidase IV [DPP-IV, EC 3.4.14.5] takes part in the metabolism of biologically active peptides participating in the regulation of growth and transformation of glial cells. However, the knowledge on the DPP-IV expression in human glial and glioma cells is still very limited. In this study, using histochemical and biochemical techniques, the DPP-IV activity was demonstrated in two commercially available human glioma cell lines of different transformation degree, as represented by U373 astrocytoma (Grade III and U87 glioblastoma multiforme (Grade IV lines. Higher total activity of the enzyme, as well as its preferential localisation in the plasma membrane, was observed in U87 cells. Compared to U373 population, U87 cells were morphologically more pleiomorphic, they were cycling at lower rate and expressing less Glial Fibrillary Acidic Protein. The data revealed positive correlation between the degree of transformation of cells and activity of DPP-IV. Great difference in expression of this enzyme, together with the phenotypic differences of cells, makes these lines a suitable standard model for further 57 studies of function of this enzyme in human glioma cells.

Rosiglitazone Reduces Plasma Levels of Inflammatory and Hemostatic Biomarkers and Improves Global Endothelial Function in Habitual Heavy Smokers Without Diabetes Mellitus or Metabolic Syndrome

Directory of Open Access Journals (Sweden)

I-Chih Chen

2010-02-01

Conclusion: Rosiglitazone significantly reduces plasma levels of inflammatory and hemostatic biomarkers, and restores global endothelial dysfunction, independently from insulin sensitization, in healthy smokers.

Plasma container

International Nuclear Information System (INIS)

Ebisawa, Katsuyuki.

1985-01-01

Purpose: To enable to easily detect that the thickness of material to be abraded is reduced to an allowable limit from the outerside of the plasma container even during usual operation in a plasma vessel for a thermonuclear device. Constitution: A labelled material is disposed to the inside or rear face of constituent members of a plasma container undergoing the irradiation of plasma particles. A limiter plate to be abraded in the plasma container is composed of an armour member and heat removing plate, in which the armour member is made of graphite and heat-removing plate is made of copper. If the armour member is continuously abraded under the effect of sputtering due to plasma particles, silicon nitride embedded so far in the graphite at last appears on the surface of the limiter plate to undergo the impact shocks of the plasma particles. Accordingly, abrasion of the limiter material can be detected by a detector comprising gas chromatography and it can easily be detected from the outside of the plasma content even during normal operation. (Horiuchi, T.)

Investigation of collisional EBW damping and its importance to EBW emission from NSTX

Czech Academy of Sciences Publication Activity Database

Urban, Jakub; Preinhaelter, Josef; Diem, S.J.; Taylor, G.; Vahala, L.; Vahala, G.

2007-01-01

Roč. 52, č. 16 (2007), s. 304-304 ISSN 0003-0503. [Annual Meeting of the Division of Plasma Physics/49th./. Orlando , Florida, 12.11.2007-16.11.2007] Institutional research plan: CEZ:AV0Z20430508 Keywords : Conversion * Emission * Tokamaks * Electron Bernstein waves * Simulation * NSTX Subject RIV: BL - Plasma and Gas Discharge Physics http://meetings.aps.org/Meeting/DPP07/Content/901

Direct Measurement of the Electron Bernstein Wave Absorption and Current Drive at the WEGA Stellarator

Czech Academy of Sciences Publication Activity Database

Laqua, H.; Marsen, S.; Otte, M.; Podoba, Y.; Preinhaelter, Josef; Urban, Jakub

2007-01-01

Roč. 52, č. 16 (2007), s. 280-280 ISSN 0003-0503. [Annual Meeting of the Division of Plasma Physics/49th./. Orlando , Florida, 12.11.2007-16.11.2007] Institutional research plan: CEZ:AV0Z20430508 Keywords : Conversion * Emission * Tokamaks * Electron Bernstein waves * Simulation * NSTX Subject RIV: BL - Plasma and Gas Discharge Physics http://meetings.aps.org/Meeting/DPP07/Content/901

Recent EBW Emission Results on NSTX

Czech Academy of Sciences Publication Activity Database

Diem, S.J.; Taylor, G.; Efthimion, P.C.; LeBlanc, B.P.; Caughman, J.B.; Bigelow, T.S.; Wilgen, J.B.; Harvey, R.W.; Preinhaelter, Josef; Urban, Jakub; Sabbagh, S.A.

2007-01-01

Roč. 52, č. 16 (2007), s. 63-63 ISSN 0003-0503. [Annual Meeting of the Division of Plasma Physics/49th./. Orlando , Florida, 12.11.2007-16.11.2007] Institutional research plan: CEZ:AV0Z20430508 Keywords : Conversion * Emission * Tokamaks * Electron Bernstein waves * Simulation * NSTX Subject RIV: BL - Plasma and Gas Discharge Physics http://meetings.aps.org/Meeting/DPP07/Content/901

Recent EBW Emission Results and Plans for a 350 kW 28 GHz EC/EBW Heating System on NSTX

Czech Academy of Sciences Publication Activity Database

Taylor, G.; Diem, S.J.; Ellis, R.A.; Fredd, E.; Greenough, N.I.; Hosea, J.C.; Bigelow, T.S.; Caughman, J.B.; Rasmussen, D.A.; Ryan, P.; Wilgen, J.B.; Harvey, R.W.; Smirnov, A.P.; Ershov, N.M.; Preinhaelter, Josef; Urban, Jakub; Ram, A.K.

2007-01-01

Roč. 52, č. 16 (2007), s. 304-304 ISSN 0003-0503. [Annual Meeting of the Division of Plasma Physics/49th./. Orlando, Florida, 12.11.2007-16.11.2007] Institutional research plan: CEZ:AV0Z20430508 Keywords : Conversion * Emission * Tokamaks * Electron Bernstein waves * Simulation * NSTX Subject RIV: BL - Plasma and Gas Discharge Physics http://meetings.aps.org/Meeting/DPP07/Content/901

Plasma position control device

International Nuclear Information System (INIS)

Takase, Haruhiko.

1987-01-01

Purpose: To conduct position control stably to various plasmas and reduce the burden on the control coil power source. Constitution: Among the proportional, integration and differentiation controls, a proportional-differentiation control section and an integration control section are connected in parallel. Then, a signal switching circuit is disposed to the control signal input section for the proportional-differentiation control section such that either a present position of plasmas or deviation between the present plasma position and an aimed value can be selected as a control signal depending on the control procedures or the state of the plasmas. For instance, if a rapid response is required for the control, the deviation between the present plasma position and the aimed value is selected as the input signal to conduct proportional, integration and differentiation controls. While on the other hand, if it is intended to reduce the burden on the control coil power source, it is adapted such that the control signal inputted to the proportional-differentiation control section itself can select the present plasma position. (Yoshihara, H.)

Air-conditioning Australian households: The impact of dynamic peak pricing

International Nuclear Information System (INIS)

Strengers, Yolande

2010-01-01

International mandates for smart metering are enabling variable and real-time pricing regimes such as dynamic peak pricing (DPP), which charges 10-40 times the off-peak rate for electricity during short periods. This regime aims to reduce peak electricity demand (predominantly due to increase in residential air-conditioning usage) and curb greenhouse gas emissions. Although trials indicate that DPP can achieve significant demand reductions, particularly in summer, little is known about how or why households change their cooling practices in response to this strategy. This paper discusses the outcomes of a small qualitative study assessing the impact of a DPP trial on household cooling practices in the Australian state of New South Wales. The study challenges common assumptions about the necessity of air-conditioning and impact of price signals. It finds that DPP engages households as co-managers of their cooling practices through a series of notification signals (SMS, phone, in-home display, email, etc.). Further, by linking the price signal to air-conditioning, some householders consider this practice discretionary for short periods of time. The paper concludes by warning that policy makers and utilities may serve to legitimise air-conditioning usage and/or negate demand reductions by failing to acknowledge the non-rational dynamics of DPP and household cooling practices. - Research highlights: →Most householders consider air-conditioning discretionary during DPP events →DPP engages householders as co-managers of their demand →Notification of an upcoming DPP event is significant to the response →Householders feel obligated to respond to DPP for a range of non-financial reasons

Plasma engineering innovations for the ORNL TNS reactor

International Nuclear Information System (INIS)

Peng, Y.K.M.; Houlberg, W.A.; Mense, A.T.; Rome, J.A.; Uckan, N.A.

1977-01-01

Recent plasma engineering studies have ascertained a viable concept for The Next Step (TNS) reactor based on medium toroidal fields between 4 T and 7 T at the plasma center, plasma β values up to 10 percent and averaged densities between 0.6 x 10 14 cm -3 and 2.5 x 10 14 cm -3 . Plasma engineering innovations that can substantially reduce the size, cost, and complexity of the TNS reactor have been explored and are summarized. It is shown that the previously anticipated requirement of high pellet velocities can be substantially reduced; the toroidal field (TF) ripple requirements may be relaxed to reduce the number of TF coils and improve machine access; hybrid equilibrium field (EF) coils have been shown to require building only small interior coils and to reduce the power supply required by the exterior coils; proper approaches of microwave plasma preheating may reduce the peak loop voltage for start-up by an order of magnitude. The medium-field TNS reactor concepts and the plasma engineering innovations discussed should be applicable to other designs of tokamak reactors

Reduced plasma noradrenaline during angiotensin II-induced acute hypertension in man

DEFF Research Database (Denmark)

Henriksen, J H; Kastrup, J; Christensen, N J

1985-01-01

1. Plasma noradrenaline and adrenaline concentrations were measured in ten subjects before, during and after intravenous infusion of angiotensin II (ANG II) in order to determine the sympathoadrenal response of ANG II challenge in man. In five subjects ganglionic blockade was additionally performed...... by intravenous infusion of trimethaphan. 2. During ANG II infusion mean arterial blood pressure increased by 30% (P adrenaline decreased less. 3. During ganglionic blockade plasma noradrenaline decreased significantly (P

Plasma immersion ion implantation for reducing metal ion release

Energy Technology Data Exchange (ETDEWEB)

Diaz, C.; Garcia, J. A.; Maendl, S.; Pereiro, R.; Fernandez, B.; Rodriguez, R. J. [Centro de Ingenieria Avanzada de Superficies AIN, 31191, Cordovilla-Pamplona (Spain); Leibniz-Institut fuer Oberflaechenmodifizierung, 04318 Leipzig (Germany); Universidad de Oviedo, Departamento Quimica Fisica y Analitica (Spain); Centro de Ingenieria Avanzada de Superficies AIN, 31191, Cordovilla-Pamplona (Spain)

2012-11-06

Plasma immersion ion implantation of Nitrogen and Oxygen on CoCrMo alloys was carried out to improve the tribological and corrosion behaviors of these biomedical alloys. In order to optimize the implantation results we were carried experiments at different temperatures. Tribocorrosion tests in bovine serum were used to measure Co, Cr and Mo releasing by using Inductively Coupled Plasma Mass Spectrometry analysis after tests. Also, X-ray Diffraction analysis were employed in order to explain any obtained difference in wear rate and corrosion tests. Wear tests reveals important decreases in rate of more than one order of magnitude for the best treatment. Moreover decreases in metal release were found for all the implanted samples, preserving the same corrosion resistance of the unimplanted samples. Finally this paper gathers an analysis, in terms of implantation parameters and achieved properties for industrial implementation of these treatments.

Similar HIV protection from four weeks of zidovudine versus nevirapine prophylaxis among formula-fed infants in Botswana

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Kathleen M. Powis

2018-03-01

Full Text Available Background: The World Health Organization HIV guidelines recommend either infant zidovudine (ZDV or nevirapine (NVP prophylaxis for the prevention of intrapartum motherto-child HIV transmission (MTCT among formula-fed infants. No study has evaluated the comparative efficacy of infant prophylaxis with twice daily ZDV versus once daily NVP in exclusively formula-fed HIV-exposed infants.   Methods: Using data from the Mpepu Study, a Botswana-based clinical trial investigating whether prophylactic co-trimoxazole could improve infant survival, retrospective analyses of MTCT events and Division of AIDS (DAIDS Grade 3 or Grade 4 occurrences of anaemia or neutropenia were performed among infants born full-term (≥ 37 weeks gestation, with a birth weight ≥ 2500 g and who were formula-fed from birth. ZDV infant prophylaxis was used from Mpepu Study inception. A protocol modification mid-way through the study led to the subsequent use of NVP infant prophylaxis.   Results: Among infants qualifying for this secondary retrospective analysis, a total of 695 (52% infants received ZDV, while 646 (48% received NVP from birth for at least 25 days but no more than 35 days. Confirmed intrapartum HIV infection occurred in two (0.29% ZDV recipients and three (0.46% NVP recipients (p = 0.68. Anaemia occurred in 19 (2.7% ZDV versus 12 (1.9% NVP (p = 0.36 recipients. Neutropenia occurred in 28 (4.0% ZDV versus 21 (3.3% NVP recipients (p = 0.47.   Conclusions: Both ZDV and NVP resulted in low intrapartum transmission rates and no significant differences in severe infant haematologic toxicity (DAIDS Grade 3 or Grade 4 among formula-fed full-term infants with a birthweight ≥ 2500 g.

Effects of Health-Related Food Taxes and Subsidies on Mortality from Diet-Related Disease in New Zealand: An Econometric-Epidemiologic Modelling Study.

Science.gov (United States)

Ni Mhurchu, Cliona; Eyles, Helen; Genc, Murat; Scarborough, Peter; Rayner, Mike; Mizdrak, Anja; Nnoaham, Kelechi; Blakely, Tony

2015-01-01

Health-related food taxes and subsidies may promote healthier diets and reduce mortality. Our aim was to estimate the effects of health-related food taxes and subsidies on deaths prevented or postponed (DPP) in New Zealand. A macrosimulation model based on household expenditure data, demand elasticities and population impact fractions for 18 diet-related diseases was used to estimate effects of five tax and subsidy regimens. We used price elasticity values for 24 major commonly consumed food groups in New Zealand, and food expenditure data from national Household Economic Surveys. Changes in mortality from cardiovascular disease, cancer, diabetes and other diet-related diseases were estimated. A 20% subsidy on fruit and vegetables would result in 560 (95% uncertainty interval, 400 to 700) DPP each year (1.9% annual all-cause mortality). A 20% tax on major dietary sources of saturated fat would result in 1,500 (950 to 2,100) DPP (5.0%), and a 20% tax on major dietary sources of sodium would result in 2,000 (1300 to 2,700) DPP (6.8%). Combining taxes on saturated fat and sodium with a fruit and vegetable subsidy would result in 2,400 (1,800 to 3,000) DPP (8.1% mortality annually). A tax on major dietary sources of greenhouse gas emissions would generate 1,200 (750 to 1,700) DPP annually (4.0%). Effects were similar or greater for Maori and low-income households in relative terms. Health-related food taxes and subsidies could improve diets and reduce mortality from diet-related disease in New Zealand. Our study adds to the growing evidence base suggesting food pricing policies should improve population health and reduce inequalities, but there is still much work to be done to improve estimation of health impacts.

Effects of Health-Related Food Taxes and Subsidies on Mortality from Diet-Related Disease in New Zealand: An Econometric-Epidemiologic Modelling Study.

Directory of Open Access Journals (Sweden)

Cliona Ni Mhurchu

Full Text Available Health-related food taxes and subsidies may promote healthier diets and reduce mortality. Our aim was to estimate the effects of health-related food taxes and subsidies on deaths prevented or postponed (DPP in New Zealand.A macrosimulation model based on household expenditure data, demand elasticities and population impact fractions for 18 diet-related diseases was used to estimate effects of five tax and subsidy regimens. We used price elasticity values for 24 major commonly consumed food groups in New Zealand, and food expenditure data from national Household Economic Surveys. Changes in mortality from cardiovascular disease, cancer, diabetes and other diet-related diseases were estimated.A 20% subsidy on fruit and vegetables would result in 560 (95% uncertainty interval, 400 to 700 DPP each year (1.9% annual all-cause mortality. A 20% tax on major dietary sources of saturated fat would result in 1,500 (950 to 2,100 DPP (5.0%, and a 20% tax on major dietary sources of sodium would result in 2,000 (1300 to 2,700 DPP (6.8%. Combining taxes on saturated fat and sodium with a fruit and vegetable subsidy would result in 2,400 (1,800 to 3,000 DPP (8.1% mortality annually. A tax on major dietary sources of greenhouse gas emissions would generate 1,200 (750 to 1,700 DPP annually (4.0%. Effects were similar or greater for Maori and low-income households in relative terms.Health-related food taxes and subsidies could improve diets and reduce mortality from diet-related disease in New Zealand. Our study adds to the growing evidence base suggesting food pricing policies should improve population health and reduce inequalities, but there is still much work to be done to improve estimation of health impacts.

Oral Administration of Sitagliptin Activates CREB and Is Neuroprotective in Murine Model of Brain Trauma

DEFF Research Database (Denmark)

DellaValle, Brian; Brix, Gitte S; Brock, Birgitte

2016-01-01

in the effects of oral treatment of a different class of GLP-1 based therapy, dipeptidyl peptidase IV (DPP-IV) inhibition on mice after TBI. DPP-IV inhibitors reduce the degradation of endogenous GLP-1 and extend circulation of this protective peptide in the bloodstream. This class has yet to be investigated...... for immunoblotting for assessment of selected biomarkers for pathology and protection. Results: Sitagliptin treatment reduced lesion size at day 2 post-injury by ~28% (p

Influence of the electron cyclotron resonance plasma confinement on reducing the bremsstrahlung production of an electron cyclotron resonance ion source with metal-dielectric structures

International Nuclear Information System (INIS)

Schachter, L.; Dobrescu, S.; Stiebing, K. E.

2009-01-01

The influence of metal-dielectric (MD) layers (MD structures) inserted into the plasma chamber of an electron cyclotron resonance ion source (ECRIS) onto the production of electron bremsstrahlung radiation has been studied in a series of dedicated experiments at the 14 GHz ECRIS of the Institut fuer Kernphysik der Universitaet Frankfurt. The IKF-ECRIS was equipped with a MD liner, covering the inner walls of the plasma chamber, and a MD electrode, covering the plasma-facing side of the extraction electrode. On the basis of similar extracted currents of highly charged ions, significantly reduced yields of bremsstrahlung radiation for the 'MD source' as compared to the standard (stainless steel) source have been measured and can be explained by the significantly better plasma confinement in a MD source as compared to an ''all stainless steel'' ECRIS.

Inhibition of dipeptidyl peptidase 4 regulates microvascular endothelial growth induced by inflammatory cytokines

International Nuclear Information System (INIS)

Takasawa, Wataru; Ohnuma, Kei; Hatano, Ryo; Endo, Yuko; Dang, Nam H.; Morimoto, Chikao

2010-01-01

Research highlights: → TNF-α or IL-1β induces EC proliferation with reduction of CD26 expression. → CD26 siRNA or DPP-4 inhibition enhances TNF-α or IL-1β-induced EC proliferation. → Loss of CD26/DPP-4 enhances aortic sprouting induced by TNF-α or IL-1β. → Capillary formation induced by TNF-α or IL-1β is enahced in the CD26 -/- mice. -- Abstract: CD26/DPP-4 is abundantly expressed on capillary of inflamed lesion as well as effector T cells. Recently, CD26/dipeptidyl peptidase 4 (DPP-4) inhibition has been used as a novel oral therapeutic approach for patients with type 2 diabetes. While accumulating data indicate that vascular inflammation is a key feature of both micro- and macro-vascular complications in diabetes, the direct role of CD26/DPP-4 in endothelial biology is to be elucidated. We herein showed that proinflammatory cytokines such as tumor necrosis factor or interleukin-1 reduce expression of CD26 on microvascular endothelial cells, and that genetical or pharmacological inhibition of CD26/DPP-4 enhances endothelial growth both in vitro and in vivo. With DPP-4 inhibitors being used widely in the treatment of type 2 diabetes, our data strongly suggest that DPP-4 inhibition plays a pivotal role in endothelial growth and may have a potential role in the recovery of local circulation following diabetic vascular complications.

Weight loss in the prevention and treatment of diabetes.

Science.gov (United States)

Delahanty, Linda M

2017-11-01

The American Diabetes Association nutrition and lifestyle recommendations for prediabetes and type 2 diabetes focus on losing 7% of body weight and increasing physical activity to at least 150minperweek. This emphasis is largely based on results of the Diabetes Prevention Program (DPP) and Look AHEAD (Action for Health in Diabetes) clinical trials. DPP demonstrated that a lifestyle intervention aimed at 7% weight loss and 150min of activity per week reduced diabetes incidence by 58% after 2.8years of follow-up and resulted in sustained improvements in hemoglobinA1c, blood pressure and lipid levels. After 15years of follow-up, DPP's lifestyle intervention sustained a 27% risk reduction in progression to diabetes. Look AHEAD's lifestyle intervention significantly reduced hemoglobinA1c, blood pressure, triglycerides, and the amount and costs of medications needed to treat these conditions when compared with diabetes support and education. Other clinical and psychological benefits achieved with lifestyle intervention were greater reductions in c-reactive protein, less self-reported retinopathy, reduced risk of nephropathy, less sexual dysfunction, decreased incidence of urinary incontinence and fatty liver, remission of sleep apnea, better physical functioning, less knee pain, more remission of diabetes, reduced incidence of depression, less body image dissatisfaction and improved quality-of-life. A number of DPP translation studies have demonstrated weight losses of 4 to 7% at 6month and 1year follow-up which has led to Medicare coverage for CDC recognized DPP lifestyle programs starting in April 2018. Translation studies of Look AHEAD using a variety of delivery formats are underway. Copyright © 2017 Elsevier Inc. All rights reserved.

[Nevirapine related hepatotoxicity: the prevalence and risk factors in a cohort of ART naive Han Chinese with AIDS].

Science.gov (United States)

Gao, Shi-cheng; Gui, Xi-en; Deng, Li-ping; Zhang, Yong-xi; Yan, Ya-jun; Rong, Yu-ping; Liang, Ke; Yang, Rong-rong

2010-09-01

To investigate the incidence of hepatotoxicity in acquired immunodeficiency syndrome (AIDS) patients on combined anti-retroviral therapy (cART) containing nevirapine (NVP) and to assess the risk factors and its impact on cART. 330 AIDS patients from March 2003 to June 2008 at local county were enrolled and a retrospective study using Kaplan-meier survival and Multivariate logistic regression modeling was conducted. 267 out of 330 patients received NVP based cART and 63 cases received EFV-based cART. The deference of prevalences of hepatotoxicity between the two groups is statistically significant (Chi2 = 6.691, P = 0.01). 133 out of 267 (49.8%) patients on NVP based cART had at least one episode of ALT elevation during a median 21 months (interquartile ranges, IQR 6, 37) follow-up time, amounts for 28.5 cases per 100 person-years. Baseline ALT elevation (OR = 14.368, P = 0.017)and HCV co-infection (OR = 3.009, P = 0.000) were risk factors for cART related hepatotoxicity, while greatly increased CD4+ T(CD4) cell count was protective against hepatotoxicity development (OR = 0.996, P = 0.000). Patients co-infected with HCV received NVP-based cART had the higher probability of hepatotoxicity than those without HCV co-infection (Log rank: Chi2 = 16.764, P = 0.000). 23 out of the 133 subjects (17.3%) with NVP related hepatotoxicity discontinued cART temporarily or shifted NVP to efavirenz. NVP related hepatotoxicity was common among ARV naive HIV infected subjects in our cohort. Baseline ALT elevation and HCV co-infection were associated statistically with the development of hepatotoxicity. Hepatotoxicity led to discontinuing cART temporarily or switching to other regimens in some subjects. It suggested that NVP should be used with caution in patients co-infected with HCV among whom anti-HCV therapy before cART initiation may contribute to minimizing the probability of NVP associated hepatotoxicity.

Dipeptidyl peptidase 4 inhibitor attenuates obesity-induced myocardial fibrosis by inhibiting transforming growth factor-βl and Smad2/3 pathways in high-fat diet-induced obesity rat model.

Science.gov (United States)

Hong, Seul-Ki; Choo, Eun-Ho; Ihm, Sang-Hyun; Chang, Kiyuk; Seung, Ki-Bae

2017-11-01

Obesity-induced myocardial fibrosis may lead to diastolic dysfunction and ultimately heart failure. Activation of the transforming growth factor (TGF)-βl and its downstream Smad2/3 pathways may play a pivotal role in the pathogenesis of obesity-induced myocardial fibrosis, and the antidiabetic dipeptidyl peptidase 4 inhibitors (DPP4i) might affect these pathways. We investigated whether DPP4i reduces myocardial fibrosis by inhibiting the TGF-β1 and Smad2/3 pathways in the myocardium of a diet-induced obesity (DIO) rat model. Eight-week-old male spontaneously hypertensive rats (SHRs) were fed either a normal fat diet (chow) or a high-fat diet (HFD) and then the HFD-fed SHRs were randomized to either the DPP4i (MK-0626) or control (distilled water) groups for 12weeks. At 20weeks old, all the rats underwent hemodynamic and metabolic studies and Doppler echocardiography. Compared with the normal fat diet (chow)-fed SHRs, the HFD-fed SHRs developed a more intense degree of hyperglycemia and dyslipidemia and showed a constellation of left ventricular (LV) diastolic dysfunction, and exacerbated myocardial fibrosis, as well as activation of the TGF-β1 and Smad2/3 pathways. DPP4i significantly improved the metabolic and hemodynamic parameters. The echocardiogram showed that DPP4i improved the LV diastolic dysfunction (early to late ventricular filling velocity [E/A] ratio, 1.49±0.21 vs. 1.77±0.09, p<0.05). Furthermore, DPP4i significantly reduced myocardial fibrosis and collagen production by the myocardium and suppressed TGF-β1 and phosphorylation of Smad2/3 in the heart. In addition, DPP4i decreased TGF-β1-induced collagen production and TGF-β1-mediated phosphorylation and nuclear translocation of Smad2/3 in rat cardiac fibroblasts. In conclusion, DPP4 inhibition attenuated myocardial fibrosis and improved LV diastolic dysfunction in a DIO rat model by modulating the TGF-β1 and Smad2/3 pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

The effects of plasma deformability on the feedback stabilization of axisymmetric modes in tokamak plasmas

International Nuclear Information System (INIS)

Ward, D.J.; Jardin, S.C.

1991-09-01

The effects of plasma deformability on the feedback stabilization of axisymmetric modes of tokamak plasmas are studied. It is seen that plasmas with strongly shaped cross sections have unstable motion different from a rigid shift. Furthermore, the placement of passive conductors is shown to modify the non-rigid components of the eigenfunction in a way that reduces the stabilizing eddy currents in these conductors. Passive feedback results using several equilibria of varying shape are presented. The eigenfunction is also modified under the effects of active feedback. This deformation is seen to depend strongly on the position of the flux loops which are used to determine plasma vertical position for the active feedback system. The variations of these non-rigid components of the eigenfunction always serve to reduce the stabilizing effect of the active feedback system by reducing the measurable poloidal flux at the flux-loop locations. Active feedback results are presented for the PBX-M tokamak configuration. (author) 19 figs., 2 tabs., 30 refs

Treatments for hyperemesis gravidarum and nausea and vomiting in pregnancy: a systematic review and economic assessment.

Science.gov (United States)

O'Donnell, Amy; McParlin, Catherine; Robson, Stephen C; Beyer, Fiona; Moloney, Eoin; Bryant, Andrew; Bradley, Jennifer; Muirhead, Colin; Nelson-Piercy, Catherine; Newbury-Birch, Dorothy; Norman, Justine; Simpson, Emma; Swallow, Brian; Yates, Laura; Vale, Luke

2016-10-01

-three studies (75 reports) met the inclusion criteria. For RCTs, 33 and 11 studies had a low and high risk of bias respectively. For the remainder ( n  = 20) it was unclear. The non-randomised studies ( n  = 9) were low quality. There were 33 separate comparators. The most common were acupressure versus placebo ( n  = 12); steroid versus usual treatment ( n  = 7); ginger versus placebo ( n  = 6); ginger versus vitamin B6 ( n  = 6); and vitamin B6 versus placebo ( n  = 4). There was evidence that ginger, antihistamines, metoclopramide (mild disease) and vitamin B6 (mild to severe disease) are better than placebo. Diclectin ® [Duchesnay Inc.; doxylamine succinate (10 mg) plus pyridoxine hydrochloride (10 mg) slow release tablet] is more effective than placebo and ondansetron is more effective at reducing nausea than pyridoxine plus doxylamine. Diclectin before symptoms of NVP begin for women at high risk of severe NVP recurrence reduces risk of moderate/severe NVP compared with taking Diclectin once symptoms begin. Promethazine is as, and ondansetron is more, effective than metoclopramide for severe NVP/HG. I.v. fluids help correct dehydration and improve symptoms. Dextrose saline may be more effective at reducing nausea than normal saline. Transdermal clonidine patches may be effective for severe HG. Enteral feeding is effective but extreme method treatment for very severe symptoms. Day case management for moderate/severe symptoms is feasible, acceptable and as effective as inpatient care. For all other interventions and comparisons, evidence is unclear. The economic analysis was limited by lack of effectiveness data, but comparison of costs between treatments highlights the implications of different choices. The main limitations were the quantity and quality of the data available. There was evidence of some improvement in symptoms for some treatments, but these data may not be transferable across disease severities. Methodologically sound and

Creatine supplementation reduces plasma levels of pro-inflammatory cytokines and PGE2 after a half-ironman competition.

Science.gov (United States)

Bassit, R A; Curi, R; Costa Rosa, L F B P

2008-08-01

The effect of creatine supplementation upon plasma levels of pro-inflammatory cytokines: Interleukin (IL) 1 beta and IL-6, Tumor Necrosis Factor alpha (TNFalpha), and Interferon alpha (INF alpha) and Prostaglandin E(2) (PGE(2)) after a half-ironman competition were investigated. Eleven triathletes, each with at least three years experience of participation in this sport were randomly divided between the control and experimental groups. During 5 days prior to competition, the control group (n = 6) was supplemented with carbohydrate (20 g x d(-1)) whereas the experimental group (n = 5) received creatine (20 g x d(-1)) in a double-blind trial. Blood samples were collected 48 h before and 24 and 48 h after competition and were used for the measurement of cytokines and PGE(2). Forty-eight hours prior to competition there was no difference between groups in the plasma concentrations (pg x ml(-1), mean +/- SEM) of IL-6 (7.08 +/- 0.63), TNFalpha (76.50 +/- 5.60), INF alpha (18.32 +/- 1.20), IL-1 beta (23.42 +/- 5.52), and PGE(2) (39.71 +/- 3.8). Twenty-four and 48 h after competition plasma levels of TNFalpha, INF alpha, IL-1 beta and PGE(2) were significantly increased (P long distance triathlon competition may reduce the inflammatory response induced by this form of strenuous of exercise.

Influence of the electron cyclotron resonance plasma confinement on reducing the bremsstrahlung production of an electron cyclotron resonance ion source with metal-dielectric structures.

Science.gov (United States)

Schachter, L; Stiebing, K E; Dobrescu, S

2009-01-01

The influence of metal-dielectric (MD) layers (MD structures) inserted into the plasma chamber of an electron cyclotron resonance ion source (ECRIS) onto the production of electron bremsstrahlung radiation has been studied in a series of dedicated experiments at the 14 GHz ECRIS of the Institut für Kernphysik der Universität Frankfurt. The IKF-ECRIS was equipped with a MD liner, covering the inner walls of the plasma chamber, and a MD electrode, covering the plasma-facing side of the extraction electrode. On the basis of similar extracted currents of highly charged ions, significantly reduced yields of bremsstrahlung radiation for the "MD source" as compared to the standard (stainless steel) source have been measured and can be explained by the significantly better plasma confinement in a MD source as compared to an "all stainless steel" ECRIS.

Use of oxidative and reducing vapor generation for reducing the detection limits of iodine in biological samples by inductively coupled plasma atomic emission spectrometry

International Nuclear Information System (INIS)

Vtorushina, Eh.A.; Saprykin, A.I.; Knapp, G.

2009-01-01

Procedures of microwave combustion in an oxygen flow and microwave acid decomposition of biological samples were optimized for the subsequent determination of iodine. A new method was proposed for the generation of molecular iodine from periodate iona using hydrogen peroxide as a reductant. Procedures were developed for determining iodine in biological samples by inductively coupled plasma atomic emission spectrometry (ICP-AES) using oxidative and reducing vapor generation; these allowed the detection limit for iodine to be lowered by 3-4 orders of magnitude. The developed procedures were used to analyze certified reference materials of milk (Skim Milk Powder BCR 150) and seaweed (Sea Lettuce BCR 279) and a Supradyn vitamin complex

Preventive effect of dipeptidyl peptidase-4 inhibitor on atherosclerosis is mainly attributable to incretin's actions in nondiabetic and diabetic apolipoprotein E-null mice.

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Michishige Terasaki

Full Text Available AIM: Several recent reports have revealed that dipeptidyl peptidase (DPP-4 inhibitors have suppressive effects on atherosclerosis in apolipoprotein E-null (Apoe (-/- mice. It remains to be seen, however, whether this effect stems from increased levels of the two active incretins, glucagon-like peptide-1 (GLP-1 and glucose-dependent insulinotropic polypeptide (GIP. METHODS: Nontreated Apoe (-/- mice, streptozotocin-induced diabetic Apoe (-/- mice, and db/db diabetic mice were administered the DPP-4 inhibitor vildagliptin in drinking water and co-infused with either saline, the GLP-1 receptor blocker, exendin(9-39, the GIP receptor blocker, (Pro(3GIP, or both via osmotic minipumps for 4 weeks. Aortic atherosclerosis and oxidized low-density lipoprotein-induced foam cell formation in exudate peritoneal macrophages were determined. RESULTS: Vildagliptin increased plasma GLP-1 and GIP levels without affecting food intake, body weight, blood pressure, or plasma lipid profile in any of the animals tested, though it reduced HbA1c in the diabetic mice. Diabetic Apoe (-/- mice exhibited further-progressed atherosclerotic lesions and foam cell formation compared with nondiabetic counterparts. Nondiabetic and diabetic Apoe (-/- mice showed a comparable response to vildagliptin, namely, remarkable suppression of atherosclerotic lesions with macrophage accumulation and foam cell formation in peritoneal macrophages. Exendin(9-39 or (Pro(3GIP partially attenuated the vildagliptin-induced suppression of atherosclerosis. The two blockers in combination abolished the anti-atherosclerotic effect of vildagliptin in nondiabetic mice but only partly attenuated it in diabetic mice. Vildagliptin suppressed macrophage foam cell formation in nondiabetic and diabetic mice, and this suppressive effect was abolished by infusions with exendin(9-39+(Pro(3GIP. Incubation of DPP-4 or vildagliptin in vitro had no effect on macrophage foam cell formation. CONCLUSIONS: Vildagliptin

Reduced plasma levels of angiotensin-(1-7 and renin activity in preeclamptic patients are associated with the angiotensin I- converting enzyme deletion/deletion genotype

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E.P. Velloso

2007-04-01

Full Text Available The relationship between preeclampsia and the renin-angiotensin system (RAS is poorly understood. Angiotensin I-converting enzyme (ACE is a key RAS component and plays an important role in blood pressure homeostasis by generating angiotensin II (Ang II and inactivating the vasodilator angiotensin-(1-7 (Ang-(1-7. ACE (I/D polymorphism is characterized by the insertion (I or deletion (D of a 287-bp fragment, leading to changes in ACE activity. In the present study, ACE (I/D polymorphism was correlated with plasma Ang-(1-7 levels and several RAS components in both preeclamptic (N = 20 and normotensive pregnant women (N = 20. The percentage of the ACE DD genotype (60% in the preeclamptic group was higher than that for the control group (35%; however, this percentage was not statistically significant (Fisher exact test = 2.86, d.f. = 2, P = 0.260. The highest plasma ACE activity was observed in the ACE DD preeclamptic women (58.1 ± 5.06 vs 27.6 ± 3.25 nmol Hip-His Leu-1 min-1 mL-1 in DD control patients; P = 0.0005. Plasma renin activity was markedly reduced in preeclampsia (0.81 ± 0.2 vs 3.43 ± 0.8 ng Ang I mL plasma-1 h-1 in DD normotensive patients; P = 0.0012. A reduced plasma level of Ang-(1-7 was also observed in preeclamptic women (15.6 ± 1.3 vs 22.7 ± 2.5 pg/mL in the DD control group; P = 0.0146. In contrast, plasma Ang II levels were unchanged in preeclamptic patients. The selective changes in the RAS described in the present study suggest that the ACE DD genotype may be used as a marker for susceptibility to preeclampsia.

Reduced plasma levels of angiotensin-(1-7 and renin activity in preeclamptic patients are associated with the angiotensin I- converting enzyme deletion/deletion genotype

Directory of Open Access Journals (Sweden)

E.P. Velloso

Full Text Available The relationship between preeclampsia and the renin-angiotensin system (RAS is poorly understood. Angiotensin I-converting enzyme (ACE is a key RAS component and plays an important role in blood pressure homeostasis by generating angiotensin II (Ang II and inactivating the vasodilator angiotensin-(1-7 (Ang-(1-7. ACE (I/D polymorphism is characterized by the insertion (I or deletion (D of a 287-bp fragment, leading to changes in ACE activity. In the present study, ACE (I/D polymorphism was correlated with plasma Ang-(1-7 levels and several RAS components in both preeclamptic (N = 20 and normotensive pregnant women (N = 20. The percentage of the ACE DD genotype (60% in the preeclamptic group was higher than that for the control group (35%; however, this percentage was not statistically significant (Fisher exact test = 2.86, d.f. = 2, P = 0.260. The highest plasma ACE activity was observed in the ACE DD preeclamptic women (58.1 ± 5.06 vs 27.6 ± 3.25 nmol Hip-His Leu-1 min-1 mL-1 in DD control patients; P = 0.0005. Plasma renin activity was markedly reduced in preeclampsia (0.81 ± 0.2 vs 3.43 ± 0.8 ng Ang I mL plasma-1 h-1 in DD normotensive patients; P = 0.0012. A reduced plasma level of Ang-(1-7 was also observed in preeclamptic women (15.6 ± 1.3 vs 22.7 ± 2.5 pg/mL in the DD control group; P = 0.0146. In contrast, plasma Ang II levels were unchanged in preeclamptic patients. The selective changes in the RAS described in the present study suggest that the ACE DD genotype may be used as a marker for susceptibility to preeclampsia.

Improvement of confinement characteristics of tokamak plasma by controlling plasma-wall interactions

International Nuclear Information System (INIS)

Sengoku, Seio

1985-08-01

Relation between plasma-wall interactions and confinement characteristics of a tokamak plasma with respect to both impurity and fuel particle controls is discussed. Following results are obtained from impurity control studies: (1) Ion sputtering is the dominant mechanism of impurity release in a steady state tokamak discharge. (2) By applying carbon coating on entire first wall of DIVA tokamak, dominant radiative region is concentrated more in boundary plasma resulting a hot peripheral plasma with cold boundary plasma. (3) A physical model of divertor functions about impurity control is empilically obtained. By a computer simulation based on above model with respect to divertor functions for JT-60 tokamak, it is found that the allowable electron temperature of the divertor plasma is not restricted by a condition that the impurity release due to ion sputtering does not increase continuously. (4) Dense and cold divertor plasma accompanied with strong remote radiative cooling was diagnosed along the magnetic field line in the simple poloidal divertor of DOUBLET III tokamak. Strong particle recycling region is found to be localized near the divertor plate. by and from particle control studies: (1) The INTOR scaling on energy confinement time is applicable to high density region when a core plasma is fueled directly by solid deuterium pellet injection in DOUBLET III tokamak. (2) As remarkably demonstrated by direct fueling with pellet injection, energy confinement characteristics can be improved at high density range by decreasing particle deposition at peripheral plasma in order to reduce plasma-wall interaction. (3) If the particle deposition at boundary layer is necessarily reduced, the electron temperature at the boundary or divertor region increases due to decrease of the particle recycling and the electron density there. (J.P.N.)

Nonlinear Plasma Waves Excitation by Intense Ion Beams in Background Plasma

International Nuclear Information System (INIS)

Kaganovich, Igor D.; Startsev, Edward A.; Davidson, Ronald C.

2004-01-01

Plasma neutralization of an intense ion pulse is of interest for many applications, including plasma lenses, heavy ion fusion, cosmic ray propagation, etc. An analytical electron fluid model has been developed to describe the plasma response to a propagating ion beam. The model predicts very good charge neutralization during quasi-steady-state propagation, provided the beam pulse duration τ b is much longer than the electron plasma period 2π/ω p , where ω p = (4πe 2 n p /m) 1/2 is the electron plasma frequency and n p is the background plasma density. In the opposite limit, the beam pulse excites large-amplitude plasma waves. If the beam density is larger than the background plasma density, the plasma waves break. Theoretical predictions are compared with the results of calculations utilizing a particle-in-cell (PIC) code. The cold electron fluid results agree well with the PIC simulations for ion beam propagation through a background plasma. The reduced fluid description derived in this paper can provide an important benchmark for numerical codes and yield scaling relations for different beam and plasma parameters. The visualization of numerical simulation data shows complex collective phenomena during beam entry and exit from the plasma

Nonlinear plasma waves excitation by intense ion beams in background plasma

International Nuclear Information System (INIS)

Kaganovich, Igor D.; Startsev, Edward A.; Davidson, Ronald C.

2004-01-01

Plasma neutralization of an intense ion pulse is of interest for many applications, including plasma lenses, heavy ion fusion, cosmic ray propagation, etc. An analytical electron fluid model has been developed to describe the plasma response to a propagating ion beam. The model predicts very good charge neutralization during quasi-steady-state propagation, provided the beam pulse duration τ b is much longer than the electron plasma period 2π/ω p , where ω p =(4πe 2 n p /m) 1/2 is the electron plasma frequency, and n p is the background plasma density. In the opposite limit, the beam pulse excites large-amplitude plasma waves. If the beam density is larger than the background plasma density, the plasma waves break. Theoretical predictions are compared with the results of calculations utilizing a particle-in-cell (PIC) code. The cold electron fluid results agree well with the PIC simulations for ion beam propagation through a background plasma. The reduced fluid description derived in this paper can provide an important benchmark for numerical codes and yield scaling relations for different beam and plasma parameters. The visualization of numerical simulation data shows complex collective phenomena during beam entry and exit from the plasma

Designing plasmas for chronic wound disinfection

International Nuclear Information System (INIS)

Nosenko, T; Shimizu, T; Morfill, G E

2009-01-01

Irradiation with low-temperature atmospheric-pressure plasma provides a promising method for chronic wound disinfection. To be efficient for this purpose, plasma should meet the following criteria: it should significantly reduce bacterial density in the wounded area, cause a long-term post-irradiation inhibition of bacterial growth, yet without causing any negative effect on human cells. In order to design plasmas that would satisfy these requirements, we assessed the relative contribution of different components with respect to bactericidal properties due to irradiation with argon plasma. We demonstrate that plasma-generated UV radiation is the main short-term sterilizing factor of argon plasma. On the other hand, plasma-generated reactive nitrogen species (RNS) and reactive oxygen species (ROS) cause a long-term 'after-irradiation' inhibition of bacterial growth and, therefore, are important for preventing wound recolonization with bacteria between two treatments. We also demonstrate that at certain concentrations plasma-generated RNS and ROS cause significant reduction of bacterial density, but have no adverse effect on human skin cells. Possible mechanisms of the different effects of plasma-generated reactive species on bacteria and human cells are discussed. The results of this study suggest that argon plasma for therapeutic purposes should be optimized in the direction of reducing the intensity of plasma-generated UV radiation and increasing the density of non-UV plasma products.

Designing plasmas for chronic wound disinfection

Energy Technology Data Exchange (ETDEWEB)

Nosenko, T; Shimizu, T; Morfill, G E [Max-Planck Institute for Extraterrestrial Physics, Garching (Germany)], E-mail: tnosenko@mpe.mpg.de

2009-11-15

Irradiation with low-temperature atmospheric-pressure plasma provides a promising method for chronic wound disinfection. To be efficient for this purpose, plasma should meet the following criteria: it should significantly reduce bacterial density in the wounded area, cause a long-term post-irradiation inhibition of bacterial growth, yet without causing any negative effect on human cells. In order to design plasmas that would satisfy these requirements, we assessed the relative contribution of different components with respect to bactericidal properties due to irradiation with argon plasma. We demonstrate that plasma-generated UV radiation is the main short-term sterilizing factor of argon plasma. On the other hand, plasma-generated reactive nitrogen species (RNS) and reactive oxygen species (ROS) cause a long-term 'after-irradiation' inhibition of bacterial growth and, therefore, are important for preventing wound recolonization with bacteria between two treatments. We also demonstrate that at certain concentrations plasma-generated RNS and ROS cause significant reduction of bacterial density, but have no adverse effect on human skin cells. Possible mechanisms of the different effects of plasma-generated reactive species on bacteria and human cells are discussed. The results of this study suggest that argon plasma for therapeutic purposes should be optimized in the direction of reducing the intensity of plasma-generated UV radiation and increasing the density of non-UV plasma products.

Production of a rapidly rotating plasma by cross-field injection of gun-produced plasma

International Nuclear Information System (INIS)

Ohzu, Akira; Ikehata, Takashi; Tanabe, Toshio; Mase, Hiroshi

1984-01-01

Cross-field plasma injection with use of a JxB plasma gun is described as a method to produce rapidly rotating plasma in a crossed electric and magnetic field system. The rotational velocity of the plasma is seriously limited by neutrals surrounding the plasma through strong interactions at the boundary layer. The concentration of neutrals can be reduced by the injection of fully or partially ionized plasma into the discharge volume instead of filling the volume with an operating gas. With use of this method, it is observed that the rotational velocity increases by a factor of 2 to 3 when compared with the conventional method of stationary gas-filling. (author)

Degradation and Stabilization of Peptide Hormones in Human Blood Specimens.

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Jizu Yi

Full Text Available Plasma hormone peptides, including GLP-1, GIP, Glucagon, and OXM, possess multiple physiological roles and potential therapeutic and diagnostic utility as biomarkers in the research of metabolic disorders. These peptides are subject to proteolytic degradation causing preanalytical variations. Stabilization for accurate quantitation of these active peptides in ex vivo blood specimens is essential for drug and biomarker development. We investigated the protease-driven instability of these peptides in conventional serum, plasma, anticoagulated whole blood, as well as whole blood and plasma stabilized with protease inhibitors. The peptide was monitored by both time-course Matrix-Assisted Laser Desorption Ionization Time-to-Flight Mass Spectrometry (MALDI -TOF MS and Ab-based assay (ELISA or RIA. MS enabled the identification of proteolytic fragments. In non-stabilized blood samples, the results clearly indicated that dipeptidyl peptidase-IV (DPP-IV removed the N-terminal two amino acid residues from GLP-1, GIP and OXM(1-37 and not-yet identified peptidase(s cleave(s the full-length OXM(1-37 and its fragments. DPP-IV also continued to remove two additional N-terminal residues of processed OXM(3-37 to yield OXM(5-37. Importantly, both DPP-IV and other peptidase(s activities were inhibited efficiently by the protease inhibitors included in the BD P800* tube. There was preservation of GLP-1, GIP, OXM and glucagon in the P800 plasma samples with half-lives > 96, 96, 72, and 45 hours at room temperature (RT, respectively. In the BD P700* plasma samples, the stabilization of GLP-1 was also achieved with half-life > 96 hours at RT. The stabilization of these variable peptides increased their utility in drug and/or biomarker development. While stability results of GLP-1 obtained with Ab-based assay were consistent with those obtained by MS analysis, the Ab-based results of GIP, Glucagon, and OXM did not reflect the time-dependent degradations revealed by MS

Interrupting prolonged sitting with brief bouts of light walking or simple resistance activities reduces resting blood pressure and plasma noradrenaline in type 2 diabetes.

Science.gov (United States)

Dempsey, Paddy C; Sacre, Julian W; Larsen, Robyn N; Straznicky, Nora E; Sethi, Parneet; Cohen, Neale D; Cerin, Ester; Lambert, Gavin W; Owen, Neville; Kingwell, Bronwyn A; Dunstan, David W

2016-12-01

Prolonged sitting is increasingly recognized as a ubiquitous cardiometabolic risk factor, possibly distinct from lack of physical exercise. We examined whether interrupting prolonged sitting with brief bouts of light-intensity activity reduced blood pressure (BP) and plasma noradrenaline in type 2 diabetes (T2D). In a randomized crossover trial, 24 inactive overweight/obese adults with T2D (14 men; mean ± SD; 62 ± 6 years) consumed standardized meals during 3 × 8 h conditions: uninterrupted sitting (SIT); sitting + half-hourly bouts of walking (3.2 km/h for 3-min) (light-intensity walking); and sitting + half-hourly bouts of simple resistance activities for 3 min (SRAs), each separated by 6-14 days washout. Resting seated BP was measured hourly (mean of three recordings, ≥20-min postactivity). Plasma noradrenaline was measured at 30-min intervals for the first hour after meals and hourly thereafter. Compared with SIT, mean resting SBP and DBP were significantly reduced (P light-intensity walking (mean ± SEM; -14 ± 1/-8 ± 1 mmHg) and SRA (-16 ± 1/-10 ± 1 mmHg), with a more pronounced effect for SRA (P light-intensity walking). Similarly, mean plasma noradrenaline was significantly reduced for both light-intensity walking (-0.3 ± 0.1 nmol/l) and SRA (-0.6 ± 0.1 nmol/l) versus SIT, with SRA lower than light-intensity walking (P light-intensity walking (-3 ± 1 bpm; P light-intensity walking or SRA reduces resting BP and plasma noradrenaline in adults with T2D, with SRA being more effective. Given the ubiquity of sedentary behaviors and poor adherence to structured exercise, this approach may have important implications for BP management in patients with T2D.

Simvastatin reduces neointimal thickening in low-density lipoprotein receptor-deficient mice after experimental angioplasty without changing plasma lipids.

Science.gov (United States)

Chen, Zhiping; Fukutomi, Tatsuya; Zago, Alexandre C; Ehlers, Raila; Detmers, Patricia A; Wright, Samuel D; Rogers, Campbell; Simon, Daniel I

2002-07-02

Statins exert antiinflammatory and antiproliferative actions independent of cholesterol lowering. To determine whether these actions might affect neointimal formation, we investigated the effect of simvastatin on the response to experimental angioplasty in LDL receptor-deficient (LDLR-/-) mice, a model of hypercholesterolemia in which changes in plasma lipids are not observed in response to simvastatin. Carotid artery dilation (2.5 atm) and complete endothelial denudation were performed in male C57BL/6J LDLR-/- mice treated with low-dose (2 mg/kg) or high-dose (20 mg/kg) simvastatin or vehicle subcutaneously 72 hours before and then daily after injury. After 7 and 28 days, intimal and medial sizes were measured and the intima to media area ratio (I:M) was calculated. Total plasma cholesterol and triglyceride levels were similar in simvastatin- and vehicle-treated mice. Intimal thickening and I:M were reduced significantly by low- and high-dose simvastatin compared with vehicle alone. Simvastatin treatment was associated with reduced cellular proliferation (BrdU), leukocyte accumulation (CD45), and platelet-derived growth factor-induced phosphorylation of the survival factor Akt and increased apoptosis after injury. Simvastatin modulates vascular repair after injury in the absence of lipid-lowering effects. Although the mechanisms are not yet established, additional research may lead to new understanding of the actions of statins and novel therapeutic interventions for preventing restenosis.

Safety of nevirapine in HIV-infected pregnant women initiating antiretroviral therapy at higher CD4 counts: a systematic review and meta-analysis.

Science.gov (United States)

Bera, Ebrahim; Mia, Rafiq

2012-10-08

The package insert for nevirapine (NVP) cautions use in HIV-infected women (including pregnant women) with CD4 counts ≥250 cells/µl. However, recent studies showed that the CD4 count of pregnant women receiving antiretroviral therapy (ART) was not predictive of NVP toxicity. To determine whether ART-naive pregnant women initiating NVP-based ART at higher CD4 counts experience greater toxicity compared with pregnant women at lower CD4 counts. We reviewed studies comparing serious adverse NVP-related events among ART-naive pregnant women who commenced therapy at higher v. lower CD4 counts. Relevant studies were extracted from PubMed, SCOPUS and EMBASE, major journals and conference proceedings prior to December 2011. Authors were contacted for additional data. Data were independently extracted and entered into Review Manager. Fourteen studies (2 663 participants) were included for analysis. The odds ratio (OR) for overall NVP toxicity among pregnant women with CD4 <250 cells/µl was 0.61 (95% confidence interval (CI) 0.43 - 0.85). When analysis was restricted to prospective studies only (7 studies, 1 318 participants), the results were consistent for overall NVP toxicity (OR 0.43; 95% CI 0.25 - 0.73) and severe hepatotoxicity (OR 0.45; 95% CI 0.22 - 0.90), but not for severe cutaneous reaction (OR 0.53; 95% CI 0.26 - 1.10). Initiating NVP-based ART during pregnancy at CD4 ≥250 cells/µl increases toxicity risk and should be avoided, necessitating urgent revision of current guidelines supporting this practice.

SEC24A deficiency lowers plasma cholesterol through reduced PCSK9 secretion

Science.gov (United States)

Chen, Xiao-Wei; Wang, He; Bajaj, Kanika; Zhang, Pengcheng; Meng, Zhuo-Xian; Ma, Danjun; Bai, Yongsheng; Liu, Hui-Hui; Adams, Elizabeth; Baines, Andrea; Yu, Genggeng; Sartor, Maureen A; Zhang, Bin; Yi, Zhengping; Lin, Jiandie; Young, Stephen G; Schekman, Randy; Ginsburg, David

2013-01-01

The secretory pathway of eukaryotic cells packages cargo proteins into COPII-coated vesicles for transport from the endoplasmic reticulum (ER) to the Golgi. We now report that complete genetic deficiency for the COPII component SEC24A is compatible with normal survival and development in the mouse, despite the fundamental role of SEC24 in COPII vesicle formation and cargo recruitment. However, these animals exhibit markedly reduced plasma cholesterol, with mutations in Apoe and Ldlr epistatic to Sec24a, suggesting a receptor-mediated lipoprotein clearance mechanism. Consistent with these data, hepatic LDLR levels are up-regulated in SEC24A-deficient cells as a consequence of specific dependence of PCSK9, a negative regulator of LDLR, on SEC24A for efficient exit from the ER. Our findings also identify partial overlap in cargo selectivity between SEC24A and SEC24B, suggesting a previously unappreciated heterogeneity in the recruitment of secretory proteins to the COPII vesicles that extends to soluble as well as trans-membrane cargoes. DOI: http://dx.doi.org/10.7554/eLife.00444.001 PMID:23580231

Scrape-off layer tokamak plasma turbulence

Science.gov (United States)

Bisai, N.; Singh, R.; Kaw, P. K.

2012-05-01

Two-dimensional (2D) interchange turbulence in the scrape-off layer of tokamak plasmas and their subsequent contribution to anomalous plasma transport has been studied in recent years using electron continuity, current balance, and electron energy equations. In this paper, numerically it is demonstrated that the inclusion of ion energy equation in the simulation changes the nature of plasma turbulence. Finite ion temperature reduces floating potential by about 15% compared with the cold ion temperature approximation and also reduces the radial electric field. Rotation of plasma blobs at an angular velocity about 1.5×105 rad/s has been observed. It is found that blob rotation keeps plasma blob charge separation at an angular position with respect to the vertical direction that gives a generation of radial electric field. Plasma blobs with high electron temperature gradients can align the charge separation almost in the radial direction. Influence of high ion temperature and its gradient has been presented.

Progress In Plasma Accelerator Development for Dynamic Formation of Plasma Liners

Science.gov (United States)

Thio, Y. C. Francis; Eskridge, Richard; Martin, Adam; Smith, James; Lee, Michael; Cassibry, Jason T.; Griffin, Steven; Rodgers, Stephen L. (Technical Monitor)

2002-01-01

An experimental plasma accelerator for magnetic target fusion (MTF) applications under development at the NASA Marshall Space Flight Center is described. The accelerator is a coaxial pulsed plasma thruster (Figure 1). It has been tested experimentally and plasma jet velocities of approx.50 km/sec have been obtained. The plasma jet has been photographed with 10-ns exposure times to reveal a stable and repeatable plasma structure (Figure 2). Data for velocity profile information has been obtained using light pipes and magnetic probes embedded in the gun walls to record the plasma and current transit respectively at various barrel locations. Preliminary spatially resolved spectral data and magnetic field probe data are also presented. A high speed triggering system has been developed and tested as a means of reducing the gun "jitter". This jitter is being characterized and future work for second generation "ultra-low jitter" gun development is being identified.

Gemigliptin: An Update of Its Clinical Use in the Management of Type 2 Diabetes Mellitus

Directory of Open Access Journals (Sweden)

Sung-Ho Kim

2016-09-01

Full Text Available Dipeptidyl peptidase-4 (DPP-4 inhibitors are a new class of oral antidiabetic agent for the treatment of type 2 diabetes mellitus. They increase endogenous levels of incretin hormones, which stimulate glucose-dependent insulin secretion, decrease glucagon secretion, and contribute to reducing postprandial hyperglycemia. Although DPP-4 inhibitors have similar benefits, they can be differentiated in terms of their chemical structure, pharmacology, efficacy and safety profiles, and clinical considerations. Gemigliptin (brand name: Zemiglo, developed by LG Life Sciences, is a potent, selective, competitive, and long acting DPP-4 inhibitor. Various studies have shown that gemigliptin is an optimized DPP-4 inhibitor in terms of efficacy, safety, and patient compliance for treatment of type 2 diabetes mellitus. In this review, we summarize the characteristics of gemigliptin and discuss its potential benefits in clinical practice.

Artichoke leaf extract (Cynara scolymus) reduces plasma cholesterol in otherwise healthy hypercholesterolemic adults: a randomized, double blind placebo controlled trial.

Science.gov (United States)

Bundy, Rafe; Walker, Ann F; Middleton, Richard W; Wallis, Carol; Simpson, Hugh C R

2008-09-01

Cardiovascular diseases are the chief causes of death in the UK, and are associated with high circulating levels of total cholesterol in the plasma. Artichoke leaf extracts (ALEs) have been reported to reduce plasma lipids levels, including total cholesterol, although high quality data is lacking. The objective of this trial was to assess the effect of ALE on plasma lipid levels and general well-being in otherwise healthy adults with mild to moderate hypercholesterolemia. 131 adults were screened for total plasma cholesterol in the range 6.0-8.0 mmol/l, with 75 suitable volunteers randomised onto the trial. Volunteers consumed 1280 mg of a standardised ALE, or matched placebo, daily for 12 weeks. Plasma total cholesterol decreased in the treatment group by an average of 4.2% (from 7.16 (SD 0.62) mmol/l to 6.86 (SD 0.68) mmol/l) and increased in the control group by an average of 1.9% (6.90 (SD 0.49) mmol/l to 7.03 (0.61) mmol/l), the difference between groups being statistically significant (p=0.025). No significant differences between groups were observed for LDL cholesterol, HDL cholesterol or triglyceride levels. General well-being improved significantly in both the treatment (11%) and control groups (9%) with no significant differences between groups. In conclusion, ALE consumption resulted in a modest but favourable statistically significant difference in total cholesterol after 12 weeks. In comparison with a previous trial, it is suggested that the apparent positive health status of the study population may have contributed to the modesty of the observed response.

Plasma Channel Lenses and Plasma Tornadoes for Optical Beam Focusing and Transport

Science.gov (United States)

Hubbard, R. F.; Kaganovich, D.; Johnson, L. A.; Gordon, D. F.; Penano, J. R.; Hafizi, B.; Helle, M. H.; Mamonau, A. A.

2017-10-01

Shaped plasmas offer the possibility of manipulating laser pulses at intensities far above the damage limits for conventional optics. An example is the plasma channel, which is a cylindrical plasma column with an on-axis density minimum. Long plasma channels have been widely used to guide intense laser pulses, particularly in laser wakefield accelerators. A new concept, the ``plasma tornado'', offers the possibility of creating long plasma channels with no nearby structures and at densities lower than can be achieved by capillary discharges. A short plasma channel can focus a laser pulse in much the same manner as a conventional lens or off-axis parabola. When placed in front of the focal point of an intense laser pulse, a plasma channel lens (PCL) can reduce the effective f-number of conventional focusing optics. When placed beyond the focal point, it can act as a collimator. We will present experimental and modeling results for a new plasma tornado design, review experimental methods for generating short PCLs, and discuss potential applications. Supported by the Naval Research Laboratory Base Program.

Neuroprotective Mechanisms of Glucagon-like Peptide-1-based Therapies in Ischaemic Stroke

DEFF Research Database (Denmark)

Marlet, Ida R; Ölmestig, Joakim N E; Vilsbøll, Tina

2018-01-01

Review was to systematically evaluate the proposed mechanism of action for GLP-1-based therapies in ischaemic brain damage in animals. We performed a literature search using MEDLINE, EMBASE and The Cochrane Library. GLP-1-based therapies administered before, during or after experimental stroke in diabetic and non......Glucagon-like peptide-1 (GLP-1)-based therapies, GLP-1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase-4 inhibitors (DPP-4Is) are widely used for the treatment of type 2 diabetes. Increasing evidence suggests that they may provide neuroprotection. The aim of this Mini......-diabetic animals were evaluated. We reviewed 27 studies comprised of 20 involving GLP-1RAs and seven involving DPP-4Is. Both GLP-1RAs and DPP-4Is affected the acute inflammatory response secondary to ischaemia by reducing inflammation, endothelial leakage and excitotoxicity. Both treatments also reduced oxidative...

The pharmacokinetic study of rutin in rat plasma based on an electrochemically reduced graphene oxide modified sensor

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Pei Zhang

2016-04-01

Full Text Available An electrochemical method based on a directly electrochemically reduced graphene oxide (ERGO film coated on a glassy carbon electrode (GCE was developed for the rapid and convenient determination of rutin in plasma. ERGO was modified on the surface of GCE by one-step electro-deposition method. Electrochemical behavior of rutin on ERGO/GCE indicated that rutin underwent a surface-controlled quasi-reversible process and the electrochemical parameters such as charge transfer coefficient (α, electron transfer number (n and electrode reaction standard rate constant (ks were 0.53, 2 and 3.4 s−1, respectively. The electrochemical sensor for rutin in plasma provided a wide linear response range of 4.70×10−7−1.25×10−5 M with the detection limit (s/n=3 of 1.84×10−8 M. The assay was successfully used to the pharmacokinetic study of rutin. The pharmacokinetic parameters such as elimination rate half-life (t1/2, area under curve (AUC, and plasma clearance (CL were calculated to be 3.345±0.647 min, 5750±656.0 µg min/mL, and 5.891±0.458 mL/min/kg, respectively. The proposed method utilized a small sample volume of 10 μL and had no complicated sample pretreatment (without deproteinization, which was simple, eco-friendly, and time- and cost-efficient for rutin pharmacokinetic studies.

Effect of Boronization on Ohmic Plasmas in NSTX

International Nuclear Information System (INIS)

Skinner, C.H.; Kugel, H.; Maingi, R.; Wampler, W.R.; Blanchard, W.; Bell, M.; Bell, R.; LeBlanc, B.; Gates, D.; Kaye, S.; LaMarche, P.; Menard, J.; Mueller, D.; Na, H.K.; Nishino, N.; Paul, S.; Sabbagh, S.; Soukhanovskii, V.

2001-01-01

Boronization of the National Spherical Torus Experiment (NSTX) has enabled access to higher density, higher confinement plasmas. A glow discharge with 4 mTorr helium and 10% deuterated trimethyl boron deposited 1.7 g of boron on the plasma facing surfaces. Ion beam analysis of witness coupons showed a B+C areal density of 10 to the 18 (B+C) cm to the -2 corresponding to a film thickness of 100 nm. Subsequent ohmic discharges showed oxygen emission lines reduced by x15, carbon emission reduced by two and copper reduced to undetectable levels. After boronization, the plasma current flattop time increased by 70% enabling access to higher density, higher confinement plasmas

Identification and optimization problems in plasma physics

International Nuclear Information System (INIS)

Gilbert, J.C.

1986-06-01

Parameter identification of the current in a tokamak plasma is studied. Plasma equilibrium in a vacuum container with a diaphragm is analyzed. A variable metric method with reduced optimization with nonlinear equality constraints; and a quasi-Newton reduced optimization method with constraints giving priority to restoration are presented [fr

Measurement of performance parameters of plasma source for plasma opening switch on Qiangguang-Ⅰ generator

International Nuclear Information System (INIS)

Luo Weixi; Zeng Zhengzhong; Lei Tianshi; Wang Liangping; Hu Yixiang; Sun Tieping; Huang Tao

2012-01-01

The plasma source (cable guns) of the plasma opening switch (POS) on Qiangguang Ⅰ generator was chosen as the study object. The plasma source performance was investigated by using charge collectors. Experimental results show that the plasma ejection density is positively correlated with the structural parameter, the distance between gun core tip and muzzle plane, and the plasma ejection velocity is negatively correlated with the parameter. The increasing rate of plasma ejection density is less than that of drive current. As far as a plasma source with tens of cable plasma guns is concerned, the influence of single cable gun's discharge dispersancy on plasma uniformity is little. Analysis of uncertainty shows that the uncertainty of measurement can be reduced by increasing the number of experiments and averaging the results. The combined standard uncertainty of plasma ejection density is less than 10%. (authors)

Serum dipeptidyl peptidase-4 activity in insulin resistant patients with non-alcoholic fatty liver disease: a novel liver disease biomarker.

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Gábor Firneisz

Full Text Available BACKGROUND: In a cross-sectional study we studied the fasting serum DPP-4 enzymatic activity (sDPP-4 and the insulin resistance index (HOMA2-IR in gliptin naïve patients with type 2 diabetes and in non-alcoholic fatty liver disease (NAFLD and in healthy controls (CNTRL. METHODS AND FINDINGS: sDPP-4 was measured by kinetic assay in 39 NAFLD (F/M:19/20, mean age: 47.42 yrs and 82 type 2 diabetes (F/M:48/34, 62.8 yrs patients and 26 (F/M:14/12, 35.3 yrs controls. Definition of T2D group as patients with type 2 diabetes but without clinically obvious liver disease created non-overlapping study groups. Diagnosis of NAFLD was based on ultrasonography and the exclusion of other etiololgy. Patients in T2D and NAFLD groups were similarly obese. 75 g CH OGTT in 39 NAFLD patients: 24-NGT, 4-IGT or IFG ("prediabetes", 11-type 2 diabetes. HOMA2-IR: CNTRL: 1.44; T2D-group: 2.62 (p = 0.046 vs CNTRL, parametric tests; NAFLD(NGTonly: 3.23 (p = 0.0013 vs CNTRL; NAFLD(IFG/IGT/type 2 diabetes: 3.82 (p<0.001 vs CNTRL, p = 0.049 vs 2TD group. sDPP-4 activity was higher in NAFLD both with NGT (mean:33.08U/L and abnormal glucose metabolism (30.38U/L than in CNTRL (25.89U/L, p<0.001 and p = 0.013 or in T2D groups (23.97U/L, p<0.001 and p = 0.004. Correlations in NAFLD among sDPP-4 and ALT: r = 0.4637,p = 0.0038 and gammaGT: r = 0.4991,p = 0.0017 and HOMA2-IR: r = 0.5295,p = 0.0026 and among HOMA2-IR and ALT: r = 0.4340,p = 0.0147 and gammaGT: r = 0.4128,p = 0.0210. CONCLUSIONS: The fasting serum DPP-4 activity was not increased in T2D provided that patients with liver disease were intentionally excluded. The high serum DPP-4 activities in NAFLD were correlated with liver tests but not with the fasting plasma glucose or HbA1C supporting that the excess is of hepatic origin and it might contribute to the speedup of metabolic deterioration. The correlation among gammaGT, ALT and serum DPP-4 activity and also between serum DPP-4 activity and HOMA2-IR in NAFLD strongly

The role of surface chemistry at ceramic/electrolyte intefaces in the generation of pulsed corona discharges in water using porous ceramic-coated rod electrodes

Czech Academy of Sciences Publication Activity Database

Lukeš, Petr; Člupek, Martin; Babický, Václav; Šunka, Pavel

2009-01-01

Roč. 6, č. 11 (2009), s. 719-728 ISSN 1612-8850 R&D Projects: GA AV ČR IAAX00430802 Institutional research plan: CEZ:AV0Z20430508 Keywords : non-thermal plasma * electrical discharge * water * surface chemistry Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 4.037, year: 2009 http://www3.interscience.wiley.com/cgi-bin/fulltext/122593644/PDFSTART

Plasma Accelerator Development for Dynamic Formation of Plasma Liners: A Status Report

Science.gov (United States)

Thio, Y. C. Francis; Eskridge, Richard; Martin, Adam; Smith, James; Lee, Michael; Rodgers, Stephen L. (Technical Monitor)

2001-01-01

An experimental plasma accelerator for magnetic target fusion (MTF) applications under development at the NASA Marshall Space Flight Center is described. The accelerator is a pulsed plasma thruster and has been tested experimentally and plasma jet velocities of approximately 50 km/sec have been obtained. The plasma jet structure has been photographed with 10 ns exposure times to reveal a stable and repeatable plasma structure. Data for velocity profile information has been obtained using light pipes embedded in the gun walls to record the plasma transit at various barrel locations. Preliminary spatially resolved spectral data and magnetic field probe data are also presented. A high speed triggering system has been developed and tested as a means of reducing the gun "jitter". This jitter is being characterized and future work for second generation "ultra-low jitter" gun development is being identified.

Hamiltonian structure of reduced fluid models for plasmas obtained from a kinetic description

International Nuclear Information System (INIS)

Guillebon, L. de; Chandre, C.

2012-01-01

We consider the Hamiltonian structure of reduced fluid models obtained from a kinetic description of collisionless plasmas by Vlasov–Maxwell equations. We investigate the possibility of finding Poisson subalgebras associated with fluid models starting from the Vlasov–Maxwell Poisson algebra. In this way, we show that the only possible Poisson subalgebra involves the moments of zeroth and first order of the Vlasov distribution, meaning the fluid density and the fluid velocity. We find that the bracket derived in [B.A. Shadwick, G.M. Tarkenton, E.H. Esarey, Phys. Rev. Lett. 93 (2004) 175002] which involves moments of order 2 is not a Poisson bracket since it does not satisfy the Jacobi identity. -- Highlights: ► We investigate fluid reductions from the Vlasov–Maxwell Poisson bracket. ► The only Poisson subalgebra involves fluid density and fluid velocity. ► The bracket derived in [B.A. Shadwick, G.M. Tarkenton, E.H. Esarey, Phys. Rev. Lett. 93 (2004) 175002] is not Hamiltonian.

Plasma and adipose tissue level of angiopoietin-like 7 (ANGPTL7) are increased in obesity and reduced after physical exercise.

Science.gov (United States)

Abu-Farha, Mohamed; Cherian, Preethi; Al-Khairi, Irina; Madhu, Dhanya; Tiss, Ali; Warsam, Samia; Alhubail, Asma; Sriraman, Devarajan; Al-Refaei, Faisal; Abubaker, Jehad

2017-01-01

ANGPTL7 is a member of the Angiopoietin-like (ANGPTL) protein family that is composed of eight proteins (1-8). Increasing evidence is associating ANGPTL proteins to obesity and insulin resistance. The biological role of ANGPTL7 is yet to be understood except for a recently proposed role in the pathophysiology of glaucoma. This study was designed to shed light on the function of ANGPTL7 in obesity and its modulation by physical exercise as well as its potential association with lipid profile. A total of 144 subjects were enrolled in this study and finished three months of physical exercise. The participants were classified based on their BMI, 82 subjects were non-obese and 62 obese. ANGPTL7 levels in plasma and adipose tissue were measured by ELISA, RT-PCR and immunohistochemistry. In this study, we showed that ANGPTL7 level was increased in the plasma of obese subjects (1249.05± 130.39 pg/mL) as compared to non-obese (930.34 ± 87.27 pg/mL) (p-Value = 0.032). ANGPTL7 Gene and protein expression levels in adipose tissue also showed over two fold increase. Physical exercise reduced circulating level of ANGPTL7 in the obese subjects to 740.98± 127.18 pg/mL, (p-Value = 0.007). ANGPTL7 expression in adipose tissue was also reduced after exercise. Finally, ANGPTL7 circulating level showed significant association with TG level in the obese subjects (R2 = 0.183, p-Value = 0.03). In conclusion, our data shows for the first time that obesity increases the level of ANGPTL7 in both plasma and adipose tissue. Increased expression of ANGPTL7 might play a minor role in the regulation of TG level in obese subjects either directly or through interaction with other ANGPTL protein members. Physical exercise reduced the level of ANGPTL7 highlighting the potential for targeting this protein as a therapeutic target for regulating dyslipidemia.

Fibrinogen Reduction During Selective Plasma Exchange due to Membrane Fouling.

Science.gov (United States)

Ohkubo, Atsushi; Okado, Tomokazu; Miyamoto, Satoko; Hashimoto, Yurie; Komori, Shigeto; Yamamoto, Motoki; Maeda, Takuma; Itagaki, Ayako; Yamamoto, Hiroko; Seshima, Hiroshi; Kurashima, Naoki; Iimori, Soichiro; Naito, Shotaro; Sohara, Eisei; Uchida, Shinichi; Rai, Tatemitsu

2017-06-01

Fibrinogen is substantially reduced by most plasmapheresis modalities but retained in selective plasma exchange using Evacure EC-4A10 (EC-4A). Although EC-4A's fibrinogen sieving coefficient is 0, a session of selective plasma exchange reduced fibrinogen by approximately 19%. Here, we investigated sieving coefficient in five patients. When the mean processed plasma volume was 1.15 × plasma volume, the mean reduction of fibrinogen during selective plasma exchange was approximately 15%. Fibrinogen sieving coefficient was 0 when the processed plasma volume was 1.0 L, increasing to 0.07 when the processed plasma volume was 3.0 L, with a mean of 0.03 during selective plasma exchange. When fibrinogen sieving coefficient was 0, selective plasma exchange reduced fibrinogen by approximately 10%. Scanning electron microscopy images revealed internal fouling of EC-4A's hollow fiber membrane by substances such as fibrinogen fibrils. Thus, fibrinogen reduction by selective plasma exchange may be predominantly caused by membrane fouling rather than filtration. © 2017 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

Relativistic plasma dielectric tensor evaluation based on the exact plasma dispersion functions concept

International Nuclear Information System (INIS)

Castejon, F.; Pavlov, S. S.

2006-01-01

The fully relativistic plasma dielectric tensor for any wave and plasma parameter is estimated on the basis of the exact plasma dispersion functions concept. The inclusion of this concept allows one to write the tensor in a closed and compact form and to reduce the tensor evaluation to the calculation of those functions. The main analytical properties of these functions are studied and two methods are given for their evaluation. The comparison between the exact dielectric tensor with the weakly relativistic approximation, widely used presently in plasma waves calculations, is given as well as the range of plasma temperature, harmonic number, and propagation angle in which the weakly relativistic approximation is valid

Improved insulin sensitivity after exercise training is linked to reduced plasma C14:0 ceramide in obesity and type 2 diabetes.

Science.gov (United States)

Kasumov, Takhar; Solomon, Thomas P J; Hwang, Calvin; Huang, Hazel; Haus, Jacob M; Zhang, Renliang; Kirwan, John P

2015-07-01

To assess the effect of exercise training on insulin sensitivity and plasma ceramides in obesity and type 2 diabetes (T2D). Twenty-four adults with obesity and normal glucose tolerance (NGT, n = 14) or diabetes (n = 10) were studied before and after a 12-week supervised exercise-training program (5 days/week, 1 h/day, 80-85% of maximum heart rate). Changes in body composition were assessed using hydrostatic weighing and computed tomography. Peripheral tissue insulin sensitivity was assessed by a 40 mU/m(2) /min hyperinsulinemic euglycemic clamp. Plasma ceramides (C14:0, C16:0, C18:0, C18:1, C20:0, C24:0, and C24:1) were quantified using electrospray ionization tandem mass spectrometry after separation with HPLC. Plasma ceramides were similar for the subjects with obesity and NGT and the subjects with diabetes, despite differences in glucose tolerance. Exercise significantly reduced body weight and adiposity and increased peripheral insulin sensitivity in both groups (P exercise training-induced improvements in insulin sensitivity, and plasma C14:0 ceramide may provide a specific target for investigating lipid-related insulin resistance in obesity and T2D. © 2015 The Obesity Society.

Pharmacological isolation of postsynaptic currents mediated by NR2A- and NR2B-containing NMDA receptors in the anterior cingulate cortex

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Cao Xiaoyan

2007-04-01

Full Text Available Abstract NMDA receptors (NMDARs are involved in excitatory synaptic transmission and plasticity associated with a variety of brain functions, from memory formation to chronic pain. Subunit-selective antagonists for NMDARs provide powerful tools to dissect NMDAR functions in neuronal activities. Recently developed antagonist for NR2A-containing receptors, NVP-AAM007, triggered debates on its selectivity and involvement of the NMDAR subunits in bi-directional synaptic plasticity. Here, we re-examined the pharmacological properties of NMDARs in the anterior cingulate cortex (ACC using NVP-AAM007 as well as ifenprodil, a selective antagonist for NR2B-containing NMDARs. By alternating sequence of drug application and examining different concentrations of NVP-AAM007, we found that the presence of NVP-AAM007 did not significantly affect the effect of ifenprodil on NMDAR-mediated EPSCs. These results suggest that NVP-AAM007 shows great preference for NR2A subunit and could be used as a selective antagonist for NR2A-containing NMDARs in the ACC.

HbA1c as a Predictor of Diabetes and as an Outcome in the Diabetes Prevention Program: A Randomized Clinical Trial

Science.gov (United States)

2015-01-01

OBJECTIVE Glycated hemoglobin (HbA1c), a standard measure of chronic glycemia for managing diabetes, has been proposed to diagnose diabetes and identify people at risk. The Diabetes Prevention Program (DPP) was a 3.2-year randomized clinical trial of preventing type 2 diabetes with a 10-year follow-up study, the DPP Outcomes Study (DPPOS). We evaluated baseline HbA1c as a predictor of diabetes and determined the effects of treatments on diabetes defined by an HbA1c ≥6.5% (48 mmol/mol). RESEARCH DESIGN AND METHODS We randomized 3,234 nondiabetic adults at high risk of diabetes to placebo, metformin, or intensive lifestyle intervention and followed them for the development of diabetes as diagnosed by fasting plasma glucose (FPG) and 2-h postload glucose (2hPG) concentrations (1997 American Diabetes Association [ADA] criteria). HbA1c was measured but not used for study eligibility or outcomes. We now evaluate treatment effects in the 2,765 participants who did not have diabetes at baseline according to FPG, 2hPG, or HbA1c (2010 ADA criteria). RESULTS Baseline HbA1c predicted incident diabetes in all treatment groups. Diabetes incidence defined by HbA1c ≥6.5% was reduced by 44% by metformin and 49% by lifestyle during the DPP and by 38% by metformin and 29% by lifestyle throughout follow-up. Unlike the primary DPP and DPPOS findings based on glucose criteria, metformin and lifestyle were similarly effective in preventing diabetes defined by HbA1c. CONCLUSIONS HbA1c predicted incident diabetes. In contrast to the superiority of the lifestyle intervention on glucose-defined diabetes, metformin and lifestyle interventions had similar effects in preventing HbA1c-defined diabetes. The long-term implications for other health outcomes remain to be determined. PMID:25336746

A Method to Construct Plasma with Nonlinear Density Enhancement Effect in Multiple Internal Inductively Coupled Plasmas

International Nuclear Information System (INIS)

Chen Zhipeng; Li Hong; Liu Qiuyan; Luo Chen; Xie Jinlin; Liu Wandong

2011-01-01

A method is proposed to built up plasma based on a nonlinear enhancement phenomenon of plasma density with discharge by multiple internal antennas simultaneously. It turns out that the plasma density under multiple sources is higher than the linear summation of the density under each source. This effect is helpful to reduce the fast exponential decay of plasma density in single internal inductively coupled plasma source and generating a larger-area plasma with multiple internal inductively coupled plasma sources. After a careful study on the balance between the enhancement and the decay of plasma density in experiments, a plasma is built up by four sources, which proves the feasibility of this method. According to the method, more sources and more intensive enhancement effect can be employed to further build up a high-density, large-area plasma for different applications. (low temperature plasma)

Doxylamine succinate–pyridoxine hydrochloride (Diclegis for the management of nausea and vomiting in pregnancy: an overview

Directory of Open Access Journals (Sweden)

Nuangchamnong N

2014-04-01

Full Text Available Nina Nuangchamnong, Jennifer Niebyl Department of Obstetrics and Gynecology, University of Iowa Hospitals and Clinics, Iowa, IA, USA Abstract: Nausea and vomiting in pregnancy (NVP is common and often undertreated, in part due to fears of adverse effects of medications on the fetus during early pregnancy. In April 2013, the US Food and Drug Administration (FDA approved doxylamine succinate 10 mg and pyridoxine hydrochloride (a vitamin B6 analog 10 mg as a delayed-release combination pill called Diclegis for the treatment of NVP. Diclegis is currently the only medication that is FDA-approved for the indication of NVP. This review addresses the historical context, safety, efficacy, pharmacology, and practical role of doxylamine and pyridoxine for the management of NVP. The reintroduction of this doxylamine–pyridoxine combination pill into the American market fills a therapeutic gap in the management of NVP left by the removal of the same active drugs marketed over 30 years ago in the form of Bendectin. The substantial amount of safety data accumulated over the years makes it one of the few drugs that qualify for FDA Pregnancy Category A status. In the hierarchical approach to pharmacological treatment of NVP, the combination of doxylamine and pyridoxine should thus be first-tier. Keywords: doxylamine, pyridoxine, vitamin B6, nausea, vomiting, pregnancy

Dynamic behavior of plasma-facing materials during plasma instabilities in tokamak reactors

International Nuclear Information System (INIS)

Hassanein, A.; Konkashbaev, I.

1997-01-01

Damage to plasma-facing and nearby components due to plasma instabilities remains a major obstacle to a successful tokamak concept. The high energy deposited on facing materials during plasma instabilities can cause severe erosion, plasma contamination, and structural failure of these components. Erosion damage can take various forms such as surface vaporization, spallation, and liquid ejection of metallic materials. Comprehensive thermodynamic and radiation hydrodynamic codes have been developed, integrated, and used to evaluate the extent of various damage to plasma-facing and nearby components. The eroded and splashed materials will be transported and then redeposited elsewhere on other plasma-facing components. Detailed physics of plasma/solid-liquid/vapor interaction in a strong magnetic field have been developed, optimized, and implemented in a self-consistent model. The plasma energy deposited in the evolving divertor debris is quickly and intensely reradiated, which may cause severe erosion and melting of other nearby components. Factors that influence and reduce vapor-shielding efficiency such as vapor diffusion and turbulence are also discussed and evaluated

A novel cupping-assisted plasma treatment for skin disinfection

Science.gov (United States)

Xiong, Zilan; Graves, David B.

2017-02-01

A novel plasma treatment method/plasma source called cupping-assisted plasma treatment/source for skin disinfection is introduced. The idea combines ancient Chinese ‘cupping’ technology with plasma sources to generate active plasma inside an isolated, pressure-controlled chamber attached to the skin. Advantages of lower pressure include reducing the threshold voltage for plasma ignition and improving the spatial uniformity of the plasma treatment. In addition, with reduced pressure inside the cup, skin pore permeability might be increased and it improves attachment of the plasma device to the skin. Moreover, at a given pressure, plasma-generated active species are restricted inside the cup, raising local reactive species concentration and enhancing the measured surface disinfection rate. A surface micro-discharge (SMD) device is used as an example of a working plasma source. We report discharge characteristics and disinfection efficiency as a function of pressure and applied voltage.

Continuous subcutaneous infusion of glucagon-like peptide 1 lowers plasma glucose and reduces appetite in type 2 diabetic patients

DEFF Research Database (Denmark)

Toft-Nielsen, M B; Madsbad, Sten; Holst, J J

1999-01-01

OBJECTIVE: The gut hormone glucagon-like peptide 1 (GLP-1) has insulinotropic and anorectic effects during intravenous infusion and has been proposed as a new treatment for type 2 diabetes and obesity. The effect of a single subcutaneous injection is brief because of rapid degradation. We therefo....... CONCLUSIONS: We conclude that 48-h continuous subcutaneous infusion of GLP-1 in type 2 diabetic patients 1) lowers fasting as well as meal-related plasma glucose, 2) reduces appetite, 3) has no gastrointestinal side effects, and 4) has no negative effect on blood pressure.......OBJECTIVE: The gut hormone glucagon-like peptide 1 (GLP-1) has insulinotropic and anorectic effects during intravenous infusion and has been proposed as a new treatment for type 2 diabetes and obesity. The effect of a single subcutaneous injection is brief because of rapid degradation. We therefore......, previously shown to lower blood glucose effectively in type 2 diabetic patients. Fasting plasma glucose (day 2) decreased from 14.1 +/- 0.9 (saline) to 12.2 +/- 0.7 mmol/l (GLP-1), P = 0.009, and 24-h mean plasma glucose decreased from 15.4 +/- 1.0 to 13.0 +/- 1.0 mmol/l, P = 0.0009. Fasting and total area...

A Protein Preload Enhances the Glucose-Lowering Efficacy of Vildagliptin in Type 2 Diabetes

DEFF Research Database (Denmark)

Wu, T; Little, TL; Bound, MJ

2016-01-01

to evaluate whether a proteinpreload could improve the efficacy of the dipeptidyl peptidase-4 (DPP-4)inhibitor vildagliptin to increase incretin concentrations, slow gastric emptying,and lower postprandial glycemia in type 2 diabetes. RESEARCH DESIGN AND METHODSTwenty-two patients with type 2 diabetes treated...... with metformin were studiedon four occasions, receiving either 50 mg vildagliptin (VILD) or placebo (PLBO) onboth the evening before and the morning of each study day. The latter dose wasfollowed after 60 min by a preload drink containing either 25 gwhey protein (WHEY)or control flavoring (CTRL), and after...... intact GLP-1 and GIP, slower gastric emptying, and lowerpostprandial glycemia (P vildagliptin to slow gastric emptying, increase plasma intactincretins, and reduce postprandial...

Effects of fueling profiles on plasma transport

International Nuclear Information System (INIS)

Mense, A.T.; Houlberg, W.A.; Attenberger, S.E.; Milora, S.L.

1978-04-01

A one-dimensional (1-D), multifluid transport model is used to investigate the effects of particle fueling profiles on plasma transport in an ignition-sized tokamak (TNS). Normal diffusive properties of plasmas will likely maintain the density at the center of the discharge even if no active fueling is provided there. This significantly relaxes the requirements for fuel penetration. Not only is lower fuel penetration easier to achieve, but it may have the advantage of reducing or eliminating density gradient-driven trapped particle microinstabilities. Simulation of discrete pellet fueling indicates that relatively low velocity (approximately 10 3 m/sec) pellets may be sufficient to fuel a TNS-sized device (approximately 1.25-m minor radius), to produce a relatively broad, cool edge region of plasma which should reduce the potential for sputtering, and also to reduce the likelihood of trapped particle mode dominated transport. Low penetrating pellets containing up to 10 to 20 percent of the total plasma ions can produce fluctuations in density and temperature at the plasma edge, but the pressure profile and fusion alpha production remain almost constant

Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing.

Directory of Open Access Journals (Sweden)

Dieter Hoffmann

Full Text Available Simple and cost-effective approaches for HIV drug-resistance testing are highly desirable for managing increasingly expanding HIV-1 infected populations who initiate antiretroviral therapy (ART, particularly in resource-limited settings. Non-nucleoside reverse trancriptase inhibitor (NNRTI-based regimens with an NRTI backbone containing lamivudine (3TC or emtricitabine (FTC are preferred first ART regimens. Failure with these drug combinations typically involves the selection of NNRTI- and/or 3TC/FTC-resistant viruses. Therefore, the availability of simple assays to measure both types of drug resistance is critical. We have developed a high throughput screening test for assessing enzymatic resistance of the HIV-1 RT in plasma to 3TC/FTC and NNRTIs. The test uses the sensitive "Amp-RT" assay with a newly-developed real-time PCR format to screen biochemically for drug resistance in single reactions containing either 3TC-triphosphate (3TC-TP or nevirapine (NVP. Assay cut-offs were defined based on testing a large panel of subtype B and non-subtype B clinical samples with known genotypic profiles. Enzymatic 3TC resistance correlated well with the presence of M184I/V, and reduced NVP susceptibility was strongly associated with the presence of K103N, Y181C/I, Y188L, and G190A/Q. The sensitivity and specificity for detecting resistance were 97.0% and 96.0% in samples with M184V, and 97.4% and 96.2% for samples with NNRTI mutations, respectively. We further demonstrate the utility of an HIV capture method in plasma by using magnetic beads coated with CD44 antibody that eliminates the need for ultracentifugation. Thus our results support the use of this simple approach for distinguishing WT from NNRTI- or 3TC/FTC-resistant viruses in clinical samples. This enzymatic testing is subtype-independent and can assist in the clinical management of diverse populations particularly in resource-limited settings.

Temperature dependence on plasma-induced damage and chemical reactions in GaN etching processes using chlorine plasma

Science.gov (United States)

Liu, Zecheng; Ishikawa, Kenji; Imamura, Masato; Tsutsumi, Takayoshi; Kondo, Hiroki; Oda, Osamu; Sekine, Makoto; Hori, Masaru

2018-06-01

Plasma-induced damage (PID) on GaN was optimally reduced by high-temperature chlorine plasma etching. Energetic ion bombardments primarily induced PID involving stoichiometry, surface roughness, and photoluminescence (PL) degradation. Chemical reactions under ultraviolet (UV) irradiation and chlorine radical exposure at temperatures higher than 400 °C can be controlled by taking into account the synergism of simultaneous photon and radical irradiations to effectively reduce PID.

Pentagone internalises glypicans to fine-tune multiple signalling pathways

Science.gov (United States)

Norman, Mark; Vuilleumier, Robin; Springhorn, Alexander; Gawlik, Jennifer; Pyrowolakis, George

2016-01-01

Tight regulation of signalling activity is crucial for proper tissue patterning and growth. Here we investigate the function of Pentagone (Pent), a secreted protein that acts in a regulatory feedback during establishment and maintenance of BMP/Dpp morphogen signalling during Drosophila wing development. We show that Pent internalises the Dpp co-receptors, the glypicans Dally and Dally-like protein (Dlp), and propose that this internalisation is important in the establishment of a long range Dpp gradient. Pent-induced endocytosis and degradation of glypicans requires dynamin- and Rab5, but not clathrin or active BMP signalling. Thus, Pent modifies the ability of cells to trap and transduce BMP by fine-tuning the levels of the BMP reception system at the plasma membrane. In addition, and in accordance with the role of glypicans in multiple signalling pathways, we establish a requirement of Pent for Wg signalling. Our data propose a novel mechanism by which morphogen signalling is regulated. DOI: http://dx.doi.org/10.7554/eLife.13301.001 PMID:27269283

Effect of eccentric exercise with reduced muscle glycogen on plasma interleukin-6 and neuromuscular responses of musculus quadriceps femoris.

Science.gov (United States)

Gavin, James P; Myers, Stephen D; Willems, Mark E T

2016-07-01

Eccentric exercise can result in muscle damage and interleukin-6 (IL-6) secretion. Glycogen availability is a potent stimulator of IL-6 secretion. We examined effects of eccentric exercise in a low-glycogen state on neuromuscular function and plasma IL-6 secretion. Twelve active men (23 ± 4 yr, 179 ± 5 cm, 77 ± 10 kg, means ± SD) completed two downhill treadmill runs (gradient, -12%, 5 × 8 min; speed, 12.1 ± 1.1 km/h) with normal (NG) and reduced muscle glycogen (RG) in randomized order and at least 6 wk apart. Muscle glycogen was reduced using an established cycling protocol until exhaustion and dietary manipulation the evening before the morning run. Physiological responses were measured up to 48 h after the downhill runs. During recovery, force deficits of musculus quadriceps femoris by maximal isometric contractions were similar. Changes in low-frequency fatigue were larger with RG. Voluntary activation and plasma IL-6 levels were similar in recovery between conditions. It is concluded that unaccustomed, damaging eccentric exercise with low muscle glycogen of the m. quadriceps femoris 1) exacerbated low-frequency fatigue but 2) had no additional effect on IL-6 secretion. Neuromuscular impairment after eccentric exercise with low muscle glycogen appears to have a greater peripheral component in early recovery. Copyright © 2016 the American Physiological Society.

Rippled plasma wall accelerating structures

International Nuclear Information System (INIS)

Cavenago, M.

1992-01-01

A concept to form a hot, pulsed, inhomogeneous plasma and to use it as a linac structure is presented. The plasma spatial distribution is controlled by an external magnetic field and by the location of thermionic emitters; microwave ECR heating at frequency ω 1 favours plasma build up and reduces plasma resistivity. A shorter microwave pulse with frequency ω 2 ≠ ω 1 excites a longitudinal mode. An expression for the maximum attainable accelerating field is found. A linearized theory of accelerating modes is given. (Author) 6 refs., 3 figs

SU-8 etching in inductively coupled oxygen plasma

DEFF Research Database (Denmark)

Rasmussen, Kristian Hagsted; Keller, Stephan Sylvest; Jensen, Flemming

2013-01-01

Structuring or removal of the epoxy based, photo sensitive polymer SU-8 by inductively coupled plasma reactive ion etching (ICP-RIE) was investigated as a function of plasma chemistry, bias power, temperature, and pressure. In a pure oxygen plasma, surface accumulation of antimony from the photo......-initiator introduced severe roughness and reduced etch rate significantly. Addition of SF6 to the plasma chemistry reduced the antimony surface concentration with lower roughness and higher etch rate as an outcome. Furthermore the etch anisotropy could be tuned by controlling the bias power. Etch rates up to 800 nm...

Plasma crowbars in cylindrical flux compression experiments

International Nuclear Information System (INIS)

Suter, L.J.

1979-01-01

We have done a series of one- and two-dimensional calculations of hard-core Z-pinch flux compression experiments in order to study the effect of a plasma on these systems. These calculations show that including a plasma can reduce the amount of flux lost during the compression. Flux losses to the outer wall of such experiments can be greatly reduced by a plasma conducting sheath which forms along the wall. This conducting sheath consists of a cold, dense high β, unmagnetized plasma which has enough pressure to balance a large field gradient. Flux which is lost into the center conductor is not effectively stopped by this plasma sheath until late in the implosion, at which time a layer similar to the one formed at the outer wall is created. Two-dimensionl simulations show that flux losses due to arching along the sliding contact of the experiment can be effectively stopped by the formation of a plasma conducting sheath

Reduced plasma taurine level in Parkinson's disease: association with motor severity and levodopa treatment.

Science.gov (United States)

Zhang, Li; Yuan, Yongsheng; Tong, Qing; Jiang, Siming; Xu, Qinrong; Ding, Jian; Zhang, Lian; Zhang, Rui; Zhang, Kezhong

2016-01-01

This study aimed to evaluate the level of taurine in plasma, and its association with the severity of motor and non-motor symptoms (NMS) and chronic levodopa treatment in Parkinson's disease (PD). Plasma taurine level was measured in treated PD (tPD), untreated PD (ntPD) and control groups. Motor symptoms and NMS were assessed using the Unified Parkinson's Disease Rating Scale, the short form of the McGill Pain Questionnaire, the Hamilton Depression Scale, the Scale for Outcomes in Parkinson's disease for Autonomic Symptoms and the Pittsburgh Sleep Quality Index. Longtime exposure to levodopa was indicated by its approximate cumulative dosage. The plasma taurine levels of PD patients were decreased when compared with controls and negatively associated with motor severity but not NMS. Moreover, tPD patients exhibited lower levels of plasma taurine than ntPD patients. Interestingly, plasma taurine levels negatively correlated with cumulative levodopa dosage in tPD. After controlling for potential confounders, the association between taurine and levodopa remained significant. Our study supports that taurine may play important roles in the pathophysiology of PD and the disturbances caused by chronic levodopa administration.

Resistivity of flame plasma in an electric field

International Nuclear Information System (INIS)

Ikuta, Kazunari.

1989-01-01

A generalized Ohm's law is obtained for a flame plasma in an electric field for the study of arc resistivity in an electromagnetic launcher (EML). The effective resistivity of flame plasma is reduced by the source, which suggests the injection of premixed combustible fuel into the arc plasma in EML in order to reduce the electron energy of the arc. The reduction of electron energy in the arc is desirable to minimize the damage of electrodes in EML. (author)

Sleep disturbances and reduced work functioning in depressive or anxiety disorders

NARCIS (Netherlands)

van Mill, J.G.; Vogelzangs, N.; Hoogendijk, W.J.G.; Penninx, B.W.J.H.

2013-01-01

Objectives: We aimed to examine the associations between sleep disturbances and work functioning in an epidemiologic cohort study in subjects with or without depressive or anxiety disorders. Methods: There were 707 subjects included in our analyses with depressive or anxiety disorders and 728

Sleep disturbances and reduced work functioning in depressive or anxiety disorders

NARCIS (Netherlands)

van Mill, Josine G.; Vogelzangs, Nicole; Hoogendijk, Witte J. G.; Penninx, Brenda W. J. H.

Objectives: We aimed to examine the associations between sleep disturbances and work functioning in an epidemiologic cohort study in subjects with or without depressive or anxiety disorders. Methods: There were 707 subjects included in our analyses with depressive or anxiety disorders and 728

EDITORIAL: Plasma jets and plasma bullets Plasma jets and plasma bullets

Science.gov (United States)

Kong, M. G.; Ganguly, B. N.; Hicks, R. F.

2012-06-01

to 1990 with only 31 papers per year on average, and a total of some 1300 papers, precedes a considerable growth of some 35-50% in research activity every five years, over the last 20 years or so. As shown in the table, the annual dissemination of the field is more than 1600 papers and the total number of papers is in excess of 20000. This upwards trajectory is typical of a strong and growing subject area in physical science, with considerable capacity in both fundamental science and applications. PeriodNumber of papersPapers per annum 1948-1990130031 1991-19952279456 1996-20003447689 2001-20054571914 2006-201066401328 2011 1658 In many of the dense plasma jets discussed above, strong physical forces generated by the plasma are often desired and this favours plasma generation at elevated gas pressure, including atmospheric pressure, which favours a high level of gas ionization. Historically it has been challenging to reduce and control the strong physical forces in high-pressure plasmas for applications where these are unwanted, for example, surface modification of polymeric sheets [5]. Indeed, there is a real need for a vast range of material processing applications at temperatures below 100oC (or below 400 K) and this favours atmospheric-pressure plasma jets sustained far from thermal equilibrium with the dissipated electrical energy largely used not in heat generation but in unleashing non-equilibrium chemical reactions. The long-standing difficulty of effectively controlling the level of gas ionization at atmospheric pressure was overcome by the technological breakthrough of achieving atmospheric-pressure glow discharges in the late 1980s [6]. A related challenge stemming from high collisionality of atmospheric-pressure plasmas (v >> ω0) means that large-area plasmas sustained between parallel-plate electrodes are very susceptible to strong plasma instabilities when molecular gases are introduced for processing applications. This led to an effective

Postpartum suppression of ovarian activity with a Deslorelin implant enhanced uterine involution in lactating dairy cows.

Science.gov (United States)

Silvestre, F T; Bartolome, J A; Kamimura, S; Arteche, A C; Pancarci, S M; Trigg, T; Thatcher, W W

2009-01-01

Holstein cows received, subcutaneously a non-degradable implant containing 5mg of the GnRH agonist Deslorelin (DESL) or no implant (CON) at 2+/-1 days postpartum (dpp). All cows were injected with PGF(2alpha) at 9 dpp. Previous pregnant (PPH) and non-pregnant uterine horns (PNPH) were determined by palpation per rectum. In Experiment 1, cows [DESL implant (n=10) and CON (n=9)] were examined by ultrasonography to record ovarian structures (23, 30 and 37 dpp) and uterine horn and cervical diameters (16, 23, 30 and 37 dpp). Uterine tone was scored before ultrasonography. Vaginoscopy was conducted just after ultrasonography examination to assess cervical discharge and color of the external cervical os. Blood samples were collected on a weekly basis for hormonal analyses. In Experiment 2, cows [DESL implant (n=77) and CON (n=70)] were palpated per rectum and vaginoscopy at 30 dpp for scoring of uterine tone, uterine horns, cervical diameter, and discharge. Blood samples were collected only at 9 dpp. In Experiment 1, DESL-implant-treated cows had more Class 1 follicles (Pscore did not differ between treatments. Treatment with non-degradable Deslorelin (5mg) implant during postpartum: (1) suppressed ovarian follicular development, (2) enhanced physical involution of the uterus and cervix, (3) increased tone of the uterine wall, (4) decreased frequency of purulent cervical discharges, and (5) reduced inflammatory processes of the reproductive tract.

MicroRNA-132 sensitizes nasopharyngeal carcinoma cells to cisplatin through regulation of forkhead box A1 protein.

Science.gov (United States)

Li, Yun-Ling; Zhao, Yi-Gang; Chen, Bin; Li, Xiao-Feng

2016-12-01

Chemoresistance in cancer is one of the major hindrances in cisplatin (DPP) treatment for nasopharyngeal carcinoma (NPC). The mechanism of such resistance remains unknown. Therefore, the present study aimed to clarify the mechanism of DDP resistance and attempted to reduce chemoresistance. Here, we found that miR-132, as a tumor suppressor, was poorly expressed in a cisplatin resistant CNE2 cell line (CNE2/DPP) accompanied with a decreased expression of miR-132 and an increased expression of FOXA1 compared with the parental cells CNE2. Exogenous overexpression of miR-132 in CNE2/DPP could sensitize their reaction to the treatment of cisplatin. In addition, FOXA1 knockdown in CNE2/DPP cells increased the chemosensitivity to DPP, suggesting the dependence of FOXA1 regulation in miR-132 activity. Moreover, miR-132 can restore cisplatin treatment response in cisplatin-resistant xenografts in vivo, while FOXA1 protein levels were decreased. In summary, our results provide novel mechanistic insights into the role of miR-132/FOXA1 signaling in the cisplatin resistance of NPC cells. Targeting of miR-132 is a potential therapeutic approach for NPC.

Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study.

Directory of Open Access Journals (Sweden)

Phairote Teeranaipong

Full Text Available Etravirine(ETR can be used for patients who have failed NNRTI-based regimen. In Thailand, ETR is approximately 45 times more expensive than rilpivirine(RPV. However, there are no data of RPV use in NNRTI failure. Therefore, we assessed the susceptibility and mutation patterns of first line NNRTI failure and the possibility of using RPV compared to ETV in patients who have failed efavirenz(EFV- and nevirapine(NVP-based regimens.Clinical samples with confirmed virological failure from EFV- or NVP-based regimens were retrospectively analyzed. Resistance-associated mutations (RAMs were interpreted by IAS-USA Drug Resistance Mutations. Susceptibility of ETR and RPV were interpreted by DUET, Monogram scoring system, and Stanford University HIV Drug Resistance Database.1,279 and 528 patients failed EFV- and NVP-based regimens, respectively. Y181C was the most common NVP-associated RAM (54.3% vs. 14.7%, p<0.01. K103N was the most common EFV-associated RAM (56.5% vs. 19.1%, P<0.01. The results from all three scoring systems were concordant. 165(11.1% and 161(10.9% patients who failed NVP-based regimen were susceptible to ETR and RPV, respectively (p = 0.85. 195 (32.2% and 191 (31.6% patients who failed EFV-based regimen, were susceptible to ETR and RPV, respectively (p = 0.79. The susceptibility of ETV and RPV in EFV failure was significantly higher than NVP failure (p<0.01.The mutation patterns for ETR and RPV were similar but 32% and 11% of patients who failed EFV and NVP -based regimen, respectivly were susceptible to RPV. This finding suggests that RPV can be used as the alternative antiretroviral agent in patients who have failed EFV-based regimen.

Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study.

Science.gov (United States)

Teeranaipong, Phairote; Sirivichayakul, Sunee; Mekprasan, Suwanna; Ohata, Pirapon June; Avihingsanon, Anchalee; Ruxrungtham, Kiat; Putcharoen, Opass

2016-01-01

Etravirine(ETR) can be used for patients who have failed NNRTI-based regimen. In Thailand, ETR is approximately 45 times more expensive than rilpivirine(RPV). However, there are no data of RPV use in NNRTI failure. Therefore, we assessed the susceptibility and mutation patterns of first line NNRTI failure and the possibility of using RPV compared to ETV in patients who have failed efavirenz(EFV)- and nevirapine(NVP)-based regimens. Clinical samples with confirmed virological failure from EFV- or NVP-based regimens were retrospectively analyzed. Resistance-associated mutations (RAMs) were interpreted by IAS-USA Drug Resistance Mutations. Susceptibility of ETR and RPV were interpreted by DUET, Monogram scoring system, and Stanford University HIV Drug Resistance Database. 1,279 and 528 patients failed EFV- and NVP-based regimens, respectively. Y181C was the most common NVP-associated RAM (54.3% vs. 14.7%, p<0.01). K103N was the most common EFV-associated RAM (56.5% vs. 19.1%, P<0.01). The results from all three scoring systems were concordant. 165(11.1%) and 161(10.9%) patients who failed NVP-based regimen were susceptible to ETR and RPV, respectively (p = 0.85). 195 (32.2%) and 191 (31.6%) patients who failed EFV-based regimen, were susceptible to ETR and RPV, respectively (p = 0.79). The susceptibility of ETV and RPV in EFV failure was significantly higher than NVP failure (p<0.01). The mutation patterns for ETR and RPV were similar but 32% and 11% of patients who failed EFV and NVP -based regimen, respectivly were susceptible to RPV. This finding suggests that RPV can be used as the alternative antiretroviral agent in patients who have failed EFV-based regimen.

Sarcoid-like lung granulomas in a hemodialysis patient treated with a dipeptidyl peptidase-4 inhibitor.

Science.gov (United States)

Sada, Ken-Ei; Wada, Jun; Morinaga, Hiroshi; Tuchimochi, Shigeyuki; Uka, Mayu; Makino, Hirofumi

2014-04-01

It has been reported that the inhibition of dipeptidyl peptidase-4 (DPP-4)/CD26 on T-cells by DPP-4 enzymatic inhibitors suppresses lymphocyte proliferation and reduces the production of various cytokines, including tumor necrosis factor (TNF)-α. A 72-year-old female with diabetic nephropathy on hemodialysis developed multiple lung nodules following the administration of vildagliptin. A biopsy demonstrated the histology of granulomas without caseous necrosis. The discontinuation of vildagliptin resulted in the disappearance of the granulomas within 4 months. As granulomatosis often develops in patients under anti-TNF-α therapy, the accumulation of DPP-4 inhibitors or its metabolites is possibly linked to unrecognized complications, such as sarcoid-like lung granulomas.

Association of folate with hearing is dependent on the 5, 10-methylenetetrahydrofolate reductase 677C-->T mutation

NARCIS (Netherlands)

Durga, J.; Anteunis, L.J.C.; Schouten, E.G.; Bots, M.L.; Kok, F.J.; Verhoef, P.

2006-01-01

Vascular disease and its risk factors have been associated with the age-related hearing loss. We examined the association of elevated plasma homocysteine and its determinants with hearing levels. Pure-tone air conduction thresholds in 728 individuals with sensorineural hearing loss were not

A Reduced-order NLTE Kinetic Model for Radiating Plasmas of Outer Envelopes of Stellar Atmospheres

Energy Technology Data Exchange (ETDEWEB)

Munafò, Alessandro [Aerospace Engineering Department, University of Illinois at Urbana-Champaign, 206A Talbot Lab., 104 S. Wright Street, Urbana, IL 61801 (United States); Mansour, Nagi N. [NASA Ames Research Center, Moffett Field, 94035 CA (United States); Panesi, Marco, E-mail: munafo@illinois.edu, E-mail: nagi.n.mansour@nasa.gov, E-mail: m.panesi@illinois.edu [Aerospace Engineering Department, University of Illinois at Urbana-Champaign, 306 Talbot Lab., 104 S. Wright Street, Urbana, IL 61801 (United States)

2017-04-01

The present work proposes a self-consistent reduced-order NLTE kinetic model for radiating plasmas found in the outer layers of stellar atmospheres. A detailed collisional-radiative kinetic mechanism is constructed by leveraging the most up-to-date set of ab initio and experimental data available in the literature. This constitutes the starting point for the derivation of a reduced-order model, obtained by lumping the bound energy states into groups. In order to determine the needed thermo-physical group properties, uniform and Maxwell–Boltzmann energy distributions are used to reconstruct the energy population of each group. Finally, the reduced set of governing equations for the material gas and the radiation field is obtained based on the moment method. Applications consider the steady flow across a shock wave in partially ionized hydrogen. The results clearly demonstrate that adopting a Maxwell–Boltzmann grouping allows, on the one hand, for a substantial reduction of the number of unknowns and, on the other, to maintain accuracy for both gas and radiation quantities. Also, it is observed that, when neglecting line radiation, the use of two groups already leads to a very accurate resolution of the photo-ionization precursor, internal relaxation, and radiative cooling regions. The inclusion of line radiation requires adopting just one additional group to account for optically thin losses in the α , β , and γ lines of the Balmer and Paschen series. This trend has been observed for a wide range of shock wave velocities.

A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects.

Science.gov (United States)

Park, Sang-In; Lee, Howard; Oh, Jaeseong; Lim, Kyoung Soo; Jang, In-Jin; Kim, Jeong-Ae; Jung, Jong Hyuk; Yu, Kyung-Sang

2015-01-01

In type 2 diabetes mellitus, fixed-dose combination (FDC) can provide the complementary benefits of correction of multiple pathophysiologic defects such as dysfunctions in glycemic or metabolic control while improving compliance compared with separate tablets taken together. The objective of the study reported here was to compare the pharmacodynamic (PD), pharmacokinetic (PK), and tolerability profiles of gemigliptin and extended-release metformin (metformin XR) between FDC and separate tablets. A randomized, open-label, single-dose, two-way, two-period, crossover study was conducted in 28 healthy male volunteers. Two FDC tablets of gemigliptin/metformin 25/500 mg or separate tablets of gemigliptin (50 mg ×1) and metformin XR (500 mg ×2) were orally administered in each period. Serial blood samples were collected up to 48 hours post-dose to determine dipeptidyl peptidase 4 (DPP-4) activity using spectrophotometric assay and concentrations of gemigliptin and metformin using tandem mass spectrometry. Geometric mean ratios (GMRs) of FDC to separate tablet formulations and their 90% confidence intervals (CIs) were calculated to compare the PD and PK parameters between the two formulations. Tolerability was assessed throughout the study. The plasma DPP-4 activity-time curves of the FDC and the separate tablets almost overlapped, leading to a GMR (90% CI) of the FDC to separate tablets for the plasma DPP-4 activity and its maximum inhibition of 1.00 (0.97-1.04) and 0.92 (0.82-1.05), respectively. Likewise, all of the GMRs (90% CIs) of FDC to separate tablets for the area under the plasma concentration-time curve and maximum plasma concentration of gemigliptin and metformin fell entirely within the conventional bioequivalence range of 0.80-1.25. Both the FDC and separate tablets were well tolerated. The PD, PK, and tolerability profiles of gemigliptin and metformin XR in FDC and separate tablets were found to be comparable. The FDC tablet of gemigliptin and metformin

DPP4/CD26/ADAbp

African Journals Online (AJOL)

corresponding to the amino acid 31-766 was subcloned into a Pichia pastoris expression vector,. pPICZ , and ... dipeptides from peptides with preferably proline or alanine ... and standard's blanks 20 µl of distilled water was added. ... Methanol as expression inducer was fed ... The pH was reduced to ~6 with acetic acid, and ...

Modeling of Optimization and Control of EBW Heating and Current Drive

Czech Academy of Sciences Publication Activity Database

Urban, Jakub; Decker, J.; Peysson, Y.; Preinhaelter, Josef; Vahala, L.; Vahala, G.

2009-01-01

Roč. 54, č. 15 (2009), s. 100-100 ISSN 0003-0503. [Annual Meeting of the APS Division of Plasma Physics/51st./. Atlanta, 02.11.2009-06.11.2009] R&D Projects: GA MŠk 7G09042; GA ČR GA202/08/0419 Institutional research plan: CEZ:AV0Z20430508 Keywords : Tokamak * Electron Bernstein wave * EBW * NSTX Subject RIV: BL - Plasma and Gas Discharge Physics http://meetings.aps.org/link/BAPS.2009.DPP.JO4.16

Plasma conditions for non-Maxwellian electron distributions in high current discharges and laser-produced plasmas

International Nuclear Information System (INIS)

Whitney, K.G.; Pulsifer, P.E.

1993-01-01

Results from the standard quasilinear theory of ion-acoustic and Langmuir plasma microturbulence are incorporated into the kinetic theory of the electron distribution function. The theory is then applied to high current discharges and laser-produced plasmas, where either the current flow or the nonlinear laser-light absorption acts, respectively, as the energy source for the microturbulence. More specifically, the theory is applied to a selenium plasma, whose charge state is determined under conditions of collisional-radiative equilibrium, and plasma conditions are found under which microturbulence strongly influences the electron kinetics. In selenium, we show that this influence extends over a wide range of plasma conditions. For ion-acoustic turbulence, a criterion is derived, analogous to one previously obtained for laser heated plasmas, that predicts when Ohmic heating dominates over electron-electron collisions. This dominance leads to the generation of electron distributions with reduced high-energy tails relative to a Maxwellian distribution of the same temperature. Ion-acoustic turbulence lowers the current requirements needed to generate these distributions. When the laser heating criterion is rederived with ion-acoustic turbulence included in the theory, a similar reduction in the laser intensity needed to produce non-Maxwellian distributions is found. Thus we show that ion-acoustic turbulence uniformly (i.e., by the same numerical factor) reduces the electrical and heat conductivities, as well as the current (squared) and laser intensity levels needed to drive the plasma into non-Maxwellian states

Transport of recycled deuterium to the plasma core in TFTR

International Nuclear Information System (INIS)

Skinner, C.H.; Bell, M.G.; Budny, R.V.; Jassby, D.L.; Park, H.; Ramsey, A.T.; Stotler, D.P.; Strachan, J.D.

1997-10-01

The authors report a study of the fueling of the plasma core by recycling in the Tokamak Fusion Test Reactor (TFTR). They have analyzed discharges fueled by deuterium recycled from the limiter and tritium-only neutral beam injection. In these plasmas, the DT neutron rate provides a measure of the deuterium influx into the core plasma. They find a reduced influx with plasmas using lithium pellet conditioning and with plasmas of reduced major (and minor) radius. Modeling with the DEGAS neutrals code shows that the dependence on radius can be related to the penetration of neutrals through the scrape-off layer

Fast capillary discharge facility CAPEX-U as a source of the soft X-ray radiation

Czech Academy of Sciences Publication Activity Database

Frolov, Oleksandr; Koláček, Karel; Schmidt, Jiří; Štraus, Jaroslav; Prukner, Václav

2007-01-01

Roč. 52, č. 16 (2007), s. 295-295 ISSN 0003-0503. [Annual Meeting of the Division of Plasma Physics/49th./. Orlando , Florida, 12.11.2007-16.11.2007] R&D Projects: GA ČR GA202/06/1324; GA AV ČR KJB100430702; GA AV ČR KAN300100702; GA MŠk 1P04LA235 Institutional research plan: CEZ:AV0Z20430508 Keywords : Capillary discharge * x-ray * laser * laser-triggered * spark gap * breakdown * plasma Subject RIV: BL - Plasma and Gas Discharge Physics http://meetings.aps.org/Meeting/DPP07/Content/901

A diet rich in high-glucoraphanin broccoli interacts with genotype to reduce discordance in plasma metabolite profiles by modulating mitochondrial function123

Science.gov (United States)

Armah, Charlotte N; Traka, Maria H; Dainty, Jack R; Defernez, Marianne; Janssens, Astrid; Leung, Wing; Doleman, Joanne F; Potter, John F

2013-01-01

Background: Observational and experimental studies suggest that diets rich in cruciferous vegetables and glucosinolates may reduce the risk of cancer and cardiovascular disease (CVD). Objective: We tested the hypothesis that a 12-wk dietary intervention with high-glucoraphanin (HG) broccoli would modify biomarkers of CVD risk and plasma metabolite profiles to a greater extent than interventions with standard broccoli or peas. Design: Subjects were randomly assigned to consume 400 g standard broccoli, 400 g HG broccoli, or 400 g peas each week for 12 wk, with no other dietary restrictions. Biomarkers of CVD risk and 347 plasma metabolites were quantified before and after the intervention. Results: No significant differences in the effects of the diets on biomarkers of CVD risk were found. Multivariate analyses of plasma metabolites identified 2 discrete phenotypic responses to diet in individuals within the HG broccoli arm, differentiated by single nucleotide polymorphisms associated with the PAPOLG gene. Univariate analysis showed effects of sex (P broccoli arm, the consequence of the intervention was to reduce variation in lipid and amino acid metabolites, tricarboxylic acid (TCA) cycle intermediates, and acylcarnitines between the 2 PAPOLG genotypes. Conclusions: The metabolic changes observed with the HG broccoli diet are consistent with a rebalancing of anaplerotic and cataplerotic reactions and enhanced integration of fatty acid β-oxidation with TCA cycle activity. These modifications may contribute to the reduction in cancer risk associated with diets that are rich in cruciferous vegetables. This trial was registered at clinicaltrials.gov as NCT01114399. PMID:23964055

Characterization of plasma menbrane polypeptides of trypanosoma from bats

OpenAIRE

Pinho,R. T.; Simone,Giovanni de

1989-01-01

Cell surface proteins of Trypanosoma dionisii, Trypanosoma vespertilionis and Trypanosoma sp. (M238) were radiodinated and their distribution both in the detergent-poor (DPP) and dertergent-enriched phase (DRP) was studied using a phase separation technique in Triton X-114 as well as polyacrylamide gel electrophoresis in sodium dodecyl sulphate (SDS-PAGE). Significant differences were observed in the proteins present in the DRP when the three species of trypanosoma were compared. Two major ba...

Spray-dried plasma and fresh frozen plasma modulate permeability and inflammation in vitro in vascular endothelial cells

NARCIS (Netherlands)

Wataha, K.; Menge, T.; Deng, X.; Shah, A.; Bode, A.; Holcomb, J.B.; Potter, D.; Kozar, R.; Spinella, P.C.; Pati, S.

2013-01-01

BACKGROUND: After major traumatic injury, patients often require multiple transfusions of fresh frozen plasma (FFP) to correct coagulopathy and to reduce bleeding. A spray-dried plasma (SDP) product has several logistical benefits over FFP use in trauma patients with coagulopathy. These benefits

Plasma rich in growth factors (PRGF-Endoret) stimulates corneal wound healing and reduces haze formation after PRK surgery.

Science.gov (United States)

Anitua, E; Muruzabal, F; Alcalde, I; Merayo-Lloves, J; Orive, G

2013-10-01

This study evaluated the efficacy of Plasma rich in growth factors (PRGF-Endoret) on the corneal wound healing process after Photorefractive keratectomy (PRK). To address this, blood from three healthy donors was collected, centrifuged and, the whole plasma column (WP) and the plasma fraction with the highest platelet concentration (F3) were collected. The effects of F3 and WP on the proliferation and migration of human corneal epithelial cells (HCE) were analyzed. PRK was performed on C57BL/6 mice. Animals were divided in three treatment groups: Control, F3, and WP. Corneal wound healing and haze formation were evaluated macroscopically. Eyes were collected at 1, 2, 3, and 7 days after surgery, and were processed for histological studies. Immunofluorescence was used to assess cellular proliferation, apoptosis and myofibroblast transformation in the mouse cornea. Results showed a significant increased on proliferation and wound healing after F3 and WP treatment when compared with control group. In vivo studies showed significant reduction on haze formation in mice treated with both PRGF-Endoret formulations (F3 and WP). Histological studies showed an increase of epithelial cell proliferation in corneas of control group, promoting an epithelial hyperplasia. The number of SMA-positive cells (corresponding to myofibroblast differentiation) was significantly lower in the PRGF-Endoret group than in the control group, correlating with the higher transparence results observed macroscopically in both PRGF-Endoret groups. According to this, it can be concluded that PRGF-Endoret accelerates corneal tissue regeneration after PRK, reducing haze formation. Copyright © 2013 Elsevier Ltd. All rights reserved.

NSTX Plasma Response to Lithium Coated Divertor

Energy Technology Data Exchange (ETDEWEB)

H.W. Kugel, M.G. Bell, J.P. Allain, R.E. Bell, S. Ding, S.P. Gerhardt, M.A. Jaworski, R. Kaita, J. Kallman, S.M. Kaye, B.P. LeBlanc, R. Maingi, R. Majeski, R. Maqueda, D.K. Mansfield, D. Mueller, R. Nygren, S.F. Paul, R. Raman, A.L. Roquemore, S.A. Sabbagh, H. Schneider, C.H. Skinner, V.A. Soukhanovskii, C.N. Taylor, J.R. Timberlak, W.R. Wampler, L.E. Zakharov, S.J. Zweben, and the NSTX Research Team

2011-01-21

NSTX experiments have explored lithium evaporated on a graphite divertor and other plasma facing components in both L- and H- mode confinement regimes heated by high-power neutral beams. Improvements in plasma performance have followed these lithium depositions, including a reduction and eventual elimination of the HeGDC time between discharges, reduced edge neutral density, reduced plasma density, particularly in the edge and the SOL, increased pedestal electron and ion temperature, improved energy confinement and the suppression of ELMs in the H-mode. However, with improvements in confinement and suppression of ELMs, there was a significant secular increase in the effective ion charge Zeff and the radiated power in H-mode plasmas as a result of increases in the carbon and medium-Z metallic impurities. Lithium itself remained at a very low level in the plasma core, <0.1%. Initial results are reported from operation with a Liquid Lithium Divertor (LLD) recently installed.

NSTX plasma response to lithium coated divertor

International Nuclear Information System (INIS)

Kugel, H.W.; Bell, M.G.; Allain, J.P.; Bell, R.E.; Ding, S.; Gerhardt, S.P.; Jaworski, M.A.; Kaita, R.; Kallman, J.; Kaye, S.M.; LeBlanc, B.P.; Maingi, Rajesh; Majeski, R.; Maqueda, R.J.; Mansfield, D.K.; Mueller, D.; Nygren, R.E.; Paul, S.F.; Raman, R.; Roquemore, A.L.; Sabbagh, S.A.; Schneider, H.; Skinner, C.H.; Soukhanovskii, V.A.; Taylor, C.N.; Timberlake, J.; Wampler, W.R.; Zakharov, L.E.; Zweben, S.J.

2011-01-01

NSTX experiments have explored lithium evaporated on a graphite divertor and other plasma-facing components in both L- and H- mode confinement regimes heated by high-power neutral beams. Improvements in plasma performance have followed these lithium depositions, including a reduction and eventual elimination of the HeGDC time between discharges, reduced edge neutral density, reduced plasma density, particularly in the edge and the SOL, increased pedestal electron and ion temperature, improved energy confinement and the suppression of ELMs in the H-mode. However, with improvements in confinement and suppression of ELMs, there was a significant secular increase in the effective ion charge Z(eff) and the radiated power in H-mode plasmas as a result of increases in the carbon and medium-Z metallic impurities. Lithium itself remained at a very low level in the plasma core, < 0.1%. Initial results are reported from operation with a Liquid Lithium Divertor (LLD) recently installed.

Assessment of plasma C-reactive protein as a biomarker of posttraumatic stress disorder risk.

Science.gov (United States)

Eraly, Satish A; Nievergelt, Caroline M; Maihofer, Adam X; Barkauskas, Donald A; Biswas, Nilima; Agorastos, Agorastos; O'Connor, Daniel T; Baker, Dewleen G

2014-04-01

Posttraumatic stress disorder (PTSD) has been associated in cross-sectional studies with peripheral inflammation. It is not known whether this observed association is the result of PTSD predisposing to inflammation (as sometimes postulated) or to inflammation predisposing to PTSD. To determine whether plasma concentration of the inflammatory marker C-reactive protein (CRP) helps predict PTSD symptoms. The Marine Resiliency Study, a prospective study of approximately 2600 war zone-deployed Marines, evaluated PTSD symptoms and various physiological and psychological parameters before deployment and at approximately 3 and 6 months following a 7-month deployment. Participants were recruited from 4 all-male infantry battalions imminently deploying to a war zone. Participation was requested of 2978 individuals; 2610 people (87.6%) consented and 2555 (85.8%) were included in the present analysis. Postdeployment data on combat-related trauma were included for 2208 participants (86.4% of the 2555 included) and on PTSD symptoms at 3 and 6 months after deployment for 1861 (72.8%) and 1617 (63.3%) participants, respectively. Severity of PTSD symptoms 3 months after deployment assessed by the Clinician-Administered PTSD Scale (CAPS). We determined the effects of baseline plasma CRP concentration on postdeployment CAPS using zero-inflated negative binomial regression (ZINBR), a procedure designed for distributions, such as CAPS in this study, that have an excess of zeroes in addition to being positively skewed. Adjusting for the baseline CAPS score, trauma exposure, and other relevant covariates, we found baseline plasma CRP concentration to be a highly significant overall predictor of postdeployment CAPS scores (P = .002): each 10-fold increment in CRP concentration was associated with an odds ratio of nonzero outcome (presence vs absence of any PTSD symptoms) of 1.51 (95% CI, 1.15-1.97; P = .003) and a fold increase in outcome with a nonzero value (extent of symptoms

Plasma total antioxidant capacity is associated with dietary intake and plasma level of antioxidants in postmenopausal women.

Science.gov (United States)

Wang, Ying; Yang, Meng; Lee, Sang-Gil; Davis, Catherine G; Kenny, Anne; Koo, Sung I; Chun, Ock K

2012-12-01

Increased plasma total antioxidant capacity (TAC) has been associated with a high consumption of fruits and vegetables. However, limited information is available on whether plasma TAC reflects the dietary intake of antioxidants and the levels of individual antioxidants in plasma. By using three different assays, the study aimed to determine if plasma TAC can effectively predict dietary intake of antioxidants and plasma antioxidant status. Forty overweight and apparently healthy postmenopausal women were recruited. Seven-day food records and 12-h fasting blood samples were collected for dietary and plasma antioxidant assessments. Plasma TAC was determined by vitamin C equivalent antioxidant capacity (VCEAC), ferric-reducing ability of plasma (FRAP) and oxygen radical absorbance capacity (ORAC) assays. TAC values determined by VCEAC were highly correlated with FRAP (r=0.79, Pantioxidants and represents more closely the plasma antioxidant levels than ORAC and FRAP. Copyright © 2012 Elsevier Inc. All rights reserved.

Deposition of porous cathodes using plasma spray technique for reduced-temperature SOFCs

Energy Technology Data Exchange (ETDEWEB)

Jankovic, J.; Hui, S.; Roller, J.; Kesler, O.; Xie, Y.; Maric, R.; Ghosh, D. [National Research Council of Canada, Vancouver, BC (Canada). Inst. for Fuel Cell Innovation

2005-07-01

Current techniques for Solid Oxide Fuel Cell (SOFC) materials deposition are often expensive and time-consuming. Plasma-spraying techniques provide higher deposition rates, short processing times and control over porosity and composition during deposition. Optimum plasma spraying for lanthanum based cathode materials were discussed. Plasma-spraying was used to deposit cathode materials onto ceramic and stainless steel substrates to obtain highly porous structures. Lanthanum cathode materials with composition of La{sub 0.6}Sr{sub 0.4}C{sub 0.2}Fe{sub 0.8}O{sub 3} were employed in the powder form. The powder was prepared from powder precursors with different power formers and binder levels, or from produced single-phase lanthanum powders. The (La{sub 0.8}Sr{sub 0.2}){sub 0.98}MnO{sub 3} cathode material was also processed for comparison purposes. The deposition process was developed to obtain coatings with good bond strength, porosity, film thickness and residual stresses. The phase and microstructure of deposited materials were characterized using X-Ray Diffraction and Scanning Electron Microscopy (SEM). It was concluded that good flow of the powder precursors is achieved by spraying 50-100 um particle size powders and using vibrating feeders. Further processing of the spraying powders was recommended. It was noted that oxide precursors showed greater reactivity among the precursors. The best precursor reactivity and coating morphology was obtained using 40 volume per cent of graphite pore former, incorporated into the precursor mixture during wet ball milling. It was concluded that higher power levels and larger distances between the plasma gun and the substrate result in coatings with the highest porosities and best phase compositions. 5 refs., 1 tab., 6 figs.

The effect of heartburn and acid reflux on the severity of nausea and vomiting of pregnancy

Science.gov (United States)

Gill, Simerpal Kaur; Maltepe, Caroline; Koren, Gideon

2009-01-01

BACKGROUND: Heartburn (HB) and acid reflux (RF) in the non-pregnant population can cause nausea and vomiting; therefore, it is plausible that in women with nausea and vomiting of pregnancy (NVP), HB/RF may increase the severity of symptoms. OBJECTIVE: To determine whether HB/RF during pregnancy contribute to increased severity of NVP. METHODS: A prospectively collected cohort of women who were experiencing NVP and HB, RF or both (n=194) was studied. The Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) scale and its Well-being scale was used to compare the severity of the study cohort’s symptoms. This cohort was compared with a group of women experiencing NVP but no HB/RF (n=188). Multiple linear regression was used to control for the effects of confounding factors. RESULTS: Women with HB/RF reported higher PUQE scores (9.6±2.6) compared with controls (8.9±2.6) (P=0.02). Similarly, Well-being scores for women experiencing HB/RF were lower (4.3±2.1) compared with controls (4.9±2.0) (P=0.01). Multiple linear regression analysis demonstrated that increased PUQE scores (P=0.003) and decreased Well-being scores (P=0.005) were due to the presence of HB/RF as opposed to confounding factors such as pre-existing gastrointestinal conditions/symptoms, hyperemesis gravidarum in previous pregnancies and comorbidities. CONCLUSION: The present cohort study is the first to demonstrate that HB/RF are associated with increased severity of NVP. Managing HB/RF may improve the severity of NVP. PMID:19373420

The stability margin of elongated plasmas

International Nuclear Information System (INIS)

Portone, Alfredo

2005-01-01

Passive stabilization is a key feature in tokamak design since it indicates the efficiency of the metallic structures to 'oppose' plasma displacements. As far as plasma vertical displacement modes are concerned, usually their passive stabilization is characterized in terms of two main indices, namely the instability growth time and the stability margin. In this study-after recalling the governing equations-we extend the definition of the stability margin given in the literature (Lazarus E. et al 1990 Nucl. Fusion 30 111, Albanese R. et al 1990 IEEE Trans. Magn. 26, Kameari A. et al 1985 Nucl. Eng. Des./Fusion 365-73) for the rigid body displacement model to the non-rigid plasma model. Numerical examples are also given for the reduced task objectives/reduced cost ITER design

Pharmacodynamics of transdermal granisetron in women with nausea and vomiting of pregnancy.

Science.gov (United States)

Caritis, Steve; Zhao, Yang; Chen, Hui-Jun; Venkataramanan, Raman

2016-07-01

Limited options exist for women with nausea and vomiting of pregnancy (NVP) who cannot tolerate oral intake. Transdermal delivery of granisetron, a 5-hydroxytryptamine-3 receptor antagonist, provides an effective alternative for such patients. The objective of this study was to evaluate the pharmacodynamics of granisetron administered intravenously (IV) and as a sustained release transdermal patch in women with NVP. We recruited 16 women with singleton gestation between 12 0/7-18 6/7 weeks who were receiving treatment for NVP and had a Pregnancy Unique Quantification of Emesis and Nausea (PUQE) score of ≥6. All consenting subjects received 1 mg of granisetron as an IV infusion over 5 minutes and blood was obtained prior to the infusion and at 10, 20, 30, and 60 minutes and at 2, 4, 6, 8, 12, and 24 hours after the start of the infusion. After a minimum washout of 48 hours after initiation of IV granisetron, a 52-cm(2) granisetron patch (34.3 mg) was placed on the upper arm of all subjects for 7 days. Blood was drawn prior to patch placement and daily thereafter for 9 days. The subjects were evaluated daily. The PUQE score was obtained from these subjects prior to the IV infusion and daily for 2 days after and again prior to and daily for 9 days after patch placement. Complete data were available in 15 women after IV administration and 13 women after patch placement. One woman stopped participation during the IV infusion while data were not available in 2 additional women after patch placement due to noncompliance. Peak plasma granisetron concentrations after IV and transdermal administration were similar (∼10 ng/mL). Prior to IV administration of granisetron, the PUQE score was 8.6 ± 1.8 (mean ± SD). The PUQE scores were significantly reduced for the ensuing 2 days (P Granisetron significantly improved symptoms of nausea and vomiting as gauged by the PUQE score. After IV infusion the reduction in PUQE score was observed within 1 day. When granisetron was

Daily grape juice consumption reduces oxidative DNA damage and plasma free radical levels in healthy Koreans

International Nuclear Information System (INIS)

Park, Yoo Kyoung; Park, Eunju; Kim, Jung-Shin; Kang, Myung-Hee

2003-01-01

Grape contains flavonoids with antioxidant properties which are believed to be protective against various types of cancer. This antioxidative protection is possibly provided by the effective scavenging of reactive oxygen species (ROS), thus defending cellular DNA from oxidative damage and potential mutations. This study of healthy adults tested whether a daily regimen of grape juice supplementation could reduce cellular DNA damage in peripheral lymphocytes and reduce the amount of free radicals released. Sixty-seven healthy volunteers (16 women and 51 men) aged 19-57 years were given 480 ml of grape juice daily for 8 weeks in addition to their normal diet, and blood samples were drawn before and after the intervention. The DNA damage was determined by using the single cell gel (comet) assay with alkaline electrophoresis and was quantified by measuring tail length (TL). Levels of free radicals were determined by reading the lucigenin-perborate ROS generating source, using the Ultra-Weak Chemiluminescence Analyzer System. Grape juice consumption resulted in a significant decrease in lymphocyte DNA damage expressed by TL (before supplementation: 88.75±1.55 μm versus after supplementation: 70.25±1.31 μm; P=0.000 by paired t-test). Additionally, grape juice consumption for 8 weeks reduced the ROS/photon count by 15%, compared to the beginning of the study. The preventive effect of grape juice against DNA damage was simultaneously shown in both sexes. These results indicate that the consumption of grape juice may increase plasma antioxidant capacity, resulting in reduced DNA damage in peripheral lymphocytes achieved at least partially by a reduced release of ROS. Our findings support the hypothesis that polyphenolic compounds contained in grape juice exert cancer-protective effects on lymphocytes, limiting oxidative DNA damage possibly via a decrease in free radical levels

Daily grape juice consumption reduces oxidative DNA damage and plasma free radical levels in healthy Koreans

Energy Technology Data Exchange (ETDEWEB)

Park, Yoo Kyoung; Park, Eunju; Kim, Jung-Shin; Kang, Myung-Hee

2003-08-28

Grape contains flavonoids with antioxidant properties which are believed to be protective against various types of cancer. This antioxidative protection is possibly provided by the effective scavenging of reactive oxygen species (ROS), thus defending cellular DNA from oxidative damage and potential mutations. This study of healthy adults tested whether a daily regimen of grape juice supplementation could reduce cellular DNA damage in peripheral lymphocytes and reduce the amount of free radicals released. Sixty-seven healthy volunteers (16 women and 51 men) aged 19-57 years were given 480 ml of grape juice daily for 8 weeks in addition to their normal diet, and blood samples were drawn before and after the intervention. The DNA damage was determined by using the single cell gel (comet) assay with alkaline electrophoresis and was quantified by measuring tail length (TL). Levels of free radicals were determined by reading the lucigenin-perborate ROS generating source, using the Ultra-Weak Chemiluminescence Analyzer System. Grape juice consumption resulted in a significant decrease in lymphocyte DNA damage expressed by TL (before supplementation: 88.75{+-}1.55 {mu}m versus after supplementation: 70.25{+-}1.31 {mu}m; P=0.000 by paired t-test). Additionally, grape juice consumption for 8 weeks reduced the ROS/photon count by 15%, compared to the beginning of the study. The preventive effect of grape juice against DNA damage was simultaneously shown in both sexes. These results indicate that the consumption of grape juice may increase plasma antioxidant capacity, resulting in reduced DNA damage in peripheral lymphocytes achieved at least partially by a reduced release of ROS. Our findings support the hypothesis that polyphenolic compounds contained in grape juice exert cancer-protective effects on lymphocytes, limiting oxidative DNA damage possibly via a decrease in free radical levels.

Electromagnetic solitons in degenerate relativistic electron–positron plasma

International Nuclear Information System (INIS)

Berezhiani, V I; Shatashvili, N L; Tsintsadze, N L

2015-01-01

The existence of soliton-like electromagnetic (EM) distributions in a fully degenerate electron–positron plasma is studied applying relativistic hydrodynamic and Maxwell equations. For a circularly polarized wave it is found that the soliton solutions exist both in relativistic as well as nonrelativistic degenerate plasmas. Plasma density in the region of soliton pulse localization is reduced considerably. The possibility of plasma cavitation is also shown. (invited comment)

Periodontal therapy reduces plasma levels of interleukin-6, C-reactive protein, and fibrinogen in patients with severe periodontitis and refractory arterial hypertension.

Science.gov (United States)

Vidal, Fábio; Figueredo, Carlos Marcelo S; Cordovil, Ivan; Fischer, Ricardo G

2009-05-01

Recent epidemiologic studies suggest that inflammation is the link between periodontal diseases and cardiovascular complications. This study aimed to evaluate the effects of non-surgical periodontal treatment on plasma levels of inflammatory markers (interleukin [IL]-6, C-reactive protein [CRP], and fibrinogen) in patients with severe periodontitis and refractory arterial hypertension. Twenty-two patients were examined and randomly divided into two groups. The test group was composed of 11 patients (mean age, 48.9 +/- 3.9 years) who received periodontal treatment, whereas the control group had 11 patients (mean age, 49.7 +/- 6.0 years) whose treatment was delayed for 3 months. Demographic and clinical periodontal data were collected, and blood tests were performed to measure the levels of IL-6, CRP, and fibrinogen at baseline and 3 months later. The clinical results showed that the mean percentages of sites with bleeding on probing, probing depth (PD) 4 to 5 mm, PD > or =6 mm, clinical attachment loss (CAL) 4 to 5 mm, and CAL > or =6 mm were significantly reduced in the test group 3 months after periodontal treatment. There were no significant differences between the data at baseline and 3 months in the control group. Periodontal treatment significantly reduced the blood levels of fibrinogen, CRP, and IL-6 in the test group. Non-surgical periodontal therapy was effective in improving periodontal clinical data and in reducing the plasma levels of IL-6, CRP, and fibrinogen in hypertensive patients with severe periodontitis.

MicroRNA-451 sensitizes lung cancer cells to cisplatin through regulation of Mcl-1.

Science.gov (United States)

Cheng, Dezhi; Xu, Yi; Sun, Changzheng; He, Zhifeng

2016-12-01

As one of the most widely used chemotherapy drugs for lung cancer, chemoresistance of cisplatin (DPP) is one of the major hindrances in treatment of this malignancy. The microRNAs (miRNAs) have been identified to mediate chemotherapy drug resistance. MiR-451 as a tumor suppressor has been evaluated its potential effect on the sensitivity of cancer cells to DDP. However, the role of miR-451 in regulatory mechanism of chemosensitivity in lung cancer cells is still largely unknown. In this study, we first constructed a cisplatin-resistant A549 cell line (A549/DPP) accompanied with a decreased expression of miR-451 and an increased expression of Mcl-1in the drug resistant cells compared with the parental cells. Exogenous expression of miR-451 level in A549/DPP was found to sensitize their reaction to the treatment of cisplatin, which coincides with reduced expression of Mcl-1. Interestingly, Mcl-1 knockdown in A549/DPP cells increased the chemosensitivity to DPP, suggesting the dependence of Mcl-1 regulation in miR-451 activity. Moreover, miR-451 can restore cisplatin treatment response in cisplatin-resistant xenografts in vivo, while Mcl-1 protein levels were decreased. Thus, these findings provided that in lung cancer cells, tumor suppressor miR-451 enhanced DPP sensitivity via regulation of Mcl-1 expression, which could be served as a novel therapeutic target for the treatment of chemotherapy resistant in lung cancer.

Phenylbutyrate reduces plasma leucine concentrations without affecting the flux of leucine

Science.gov (United States)

Phenylbutyrate (PB) has been used as an alternative pathway to excrete nitrogen in urea cycle disorder patients for the last 20 years. PB, after oxidation to phenylacetate, is conjugated with glutamine and excreted in the urine. A reduction in the plasma concentration of branched amino acids (BCAA) ...

All-cause mortality and cardiovascular effects associated with the DPP-IV inhibitor sitagliptin compared with metformin, a retrospective cohort study on the Danish population

DEFF Research Database (Denmark)

Scheller, N M; Mogensen, U M; Andersson, Charlotte

2014-01-01

we analysed the hazard ratio of changing treatment. RESULTS: A total of 84 756 patients were included in the analysis, 1228 (1.4%) received sitagliptin monotherapy whereas the remaining 83 528 (98.6%) patients received metformin monotherapy. Patients using metformin were younger than patients using...... sitagliptin (59.0 ± 15.2 vs. 62.5 ± 13.1) were less often male (51.6 vs. 54.2%) and had longer treatment duration with monotherapy (1.8 ± 1.3 vs. 0.9 ± 1.1 years). Compared with patients receiving metformin, patients using sitagliptin showed no statistically significant excess risks of all-cause mortality......AIM: We performed a retrospective cohort study, investigating the clinical outcomes including mortality and cardiovascular disease of sitagliptin compared with metformin monotherapies. METHODS: All patients receiving monotherapy with the dipeptidyl peptidase-IV inhibitors (DPP-IV) inhibitor...

GLP-1-(9-36) amide reduces blood glucose in anesthetized pigs by a mechanism that does not involve insulin secretion

DEFF Research Database (Denmark)

Deacon, Carolyn F; Plamboeck, Astrid; Møller, Søren

2002-01-01

impossible to assess its true efficacy in vivo. In chloralose-anesthetized pigs given valine-pyrrolidide (to block endogenous DPP IV activity), the independent effects of GLP-1-(7-36) amide on glucose and insulin responses to intravenous glucose were assessed, and the metabolite generated by DPP IV, GLP-1......-(9-36) amide, was investigated for any ability to influence these responses. GLP-1-(7-36) amide enhanced insulin secretion (P amide was without effect, either alone or when coinfused with GLP-1-(7-36) amide. In contrast, GLP-1-(9-36) amide did affect glucose responses (P...... amide (73 +/- 19 mmol x l(-1) x min; P amide (62 +/- 13 mmol x l(-1) x min; P amide + GLP-1-(9-36) amide (50 +/-13 mmol x l(-1) x min; P

TOPICAL REVIEW: Plasma assisted ignition and combustion

Science.gov (United States)

Starikovskaia, S. M.

2006-08-01

In recent decades particular interest in applications of nonequilibrium plasma for the problems of plasma-assisted ignition and plasma-assisted combustion has been observed. A great amount of experimental data has been accumulated during this period which provided the grounds for using low temperature plasma of nonequilibrium gas discharges for a number of applications at conditions of high speed flows and also at conditions similar to automotive engines. The paper is aimed at reviewing the data obtained and discusses their treatment. Basic possibilities of low temperature plasma to ignite gas mixtures are evaluated and historical references highlighting pioneering works in the area are presented. The first part of the review discusses plasmas applied to plasma-assisted ignition and combustion. The paper pays special attention to experimental and theoretical analysis of some plasma parameters, such as reduced electric field, electron density and energy branching for different gas discharges. Streamers, pulsed nanosecond discharges, dielectric barrier discharges, radio frequency discharges and atmospheric pressure glow discharges are considered. The second part depicts applications of discharges to reduce the ignition delay time of combustible mixtures, to ignite transonic and supersonic flows, to intensify ignition and to sustain combustion of lean mixtures. The results obtained by different authors are cited, and ways of numerical modelling are discussed. Finally, the paper draws some conclusions on the main achievements and prospects of future investigations in the field.

Modelling of neutral particle transport in divertor plasma

International Nuclear Information System (INIS)

Kakizuka, Tomonori; Shimizu, Katsuhiro

1995-01-01

An outline of the modelling of neutral particle transport in the diverter plasma was described in the paper. The characteristic properties of divertor plasma were largely affected by interaction between neutral particles and divertor plasma. Accordingly, the behavior of neutral particle should be investigated quantitatively. Moreover, plasma and neutral gas should be traced consistently in the plasma simulation. There are Monte Carlo modelling and the neutral gas fluid modelling as the transport modelling. The former need long calculation time, but it is able to make the physical process modelling. A ultra-large parallel computer is good for the former. In spite of proposing some kinds of models, the latter has not been established. At the view point of reducing calculation time, a work station is good for the simulation of the latter, although some physical problems have not been solved. On the Monte Carlo method particle modelling, reducing the calculation time and introducing the interaction of particles are important subjects to develop 'the evolutional Monte Carlo Method'. To reduce the calculation time, two new methods: 'Implicit Monte Carlo method' and 'Free-and Diffusive-Motion Hybrid Monte-Carlo method' have been developing. (S.Y.)

Low plasma progranulin levels in children with autism

Directory of Open Access Journals (Sweden)

Mostafa Gehan A

2011-09-01

Full Text Available Abstract Background Autoimmunity to brain may play a pathogenic role in autism. In autoimmune disorders, the formation of antigen-antibody complexes triggers an inflammatory response by inducing the infiltration of neutrophils. Local administration of recombinant progranulin, which is an anti-inflammatory neurotrophic factor, potently inhibit neutrophilic inflammation in vivo, demonstrating that progranulin represents a crucial inflammation-suppressing mediator. We are the first to measure plasma progranulin levels in autism. Methods Plasma levels of progranulin were measured, by ELISA, in 40 autistic patients, aged between 3 and 12 years, and 40 healthy-matched children. Results Autistic children had significantly lower plasma progranulin levels, P = 0.001. Reduced plasma progranulin levels were found in 65% (26/40 of autistic children. On the other hand, there was a non significant difference between plasma progranulin levels of children with mild to moderate autism and patients with severe autism, P = 0.11. Conclusions Plasma progranulin levels were reduced in a subgroup of patients with autism. Progranulin insufficiency in some patients with autism may result in many years of reduced neutrotrophic support together with cumulative damage in association with dysregulated inflammation that may have a role in autism. However, these data should be treated with caution until further investigations are performed, with a larger subject population, to determine whether the decrease of plasma progranulin levels is a mere consequence of autism or has a pathogenic role in the disease. The role of progranulin therapy should also be studied in autism.

Low plasma progranulin levels in children with autism.

Science.gov (United States)

Al-Ayadhi, Laila Y; Mostafa, Gehan A

2011-09-05

Autoimmunity to brain may play a pathogenic role in autism. In autoimmune disorders, the formation of antigen-antibody complexes triggers an inflammatory response by inducing the infiltration of neutrophils. Local administration of recombinant progranulin, which is an anti-inflammatory neurotrophic factor, potently inhibit neutrophilic inflammation in vivo, demonstrating that progranulin represents a crucial inflammation-suppressing mediator. We are the first to measure plasma progranulin levels in autism. Plasma levels of progranulin were measured, by ELISA, in 40 autistic patients, aged between 3 and 12 years, and 40 healthy-matched children. Autistic children had significantly lower plasma progranulin levels, P = 0.001. Reduced plasma progranulin levels were found in 65% (26/40) of autistic children.On the other hand, there was a non significant difference between plasma progranulin levels of children with mild to moderate autism and patients with severe autism, P = 0.11. Plasma progranulin levels were reduced in a subgroup of patients with autism. Progranulin insufficiency in some patients with autism may result in many years of reduced neutrotrophic support together with cumulative damage in association with dysregulated inflammation that may have a role in autism. However, these data should be treated with caution until further investigations are performed, with a larger subject population, to determine whether the decrease of plasma progranulin levels is a mere consequence of autism or has a pathogenic role in the disease. The role of progranulin therapy should also be studied in autism.

Transport barriers in plasmas

International Nuclear Information System (INIS)

Caldas, I L; Szezech, J D Jr; Kroetz, T; Marcus, F A; Roberto, M; Viana, R L; Lopes, S R

2012-01-01

We discuss the creation of transport barriers in magnetically confined plasmas with non monotonic equilibrium radial profiles. These barriers reduce the transport in the shearless region (i.e., where the twist condition does not hold). For the chaotic motion of particles in an equilibrium electric field with a nonmonotonic radial profile, perturbed by electrostatic waves, we show that a nontwist transport barrier can be created in the plasma by modifying the electric field radial profile. We also show non twist barriers in chaotic magnetic field line transport in the plasma near to the tokamak wall with resonant modes due to electric currents in external coils.

Plasma control device

International Nuclear Information System (INIS)

Matsutomi, Akiyoshi.

1995-01-01

Plasma position and shape estimation values are outputted based on measured values of coil current. When the measured values of the position and the shape are judged to be abnormal, position and shape estimation values estimated by a plasma position and shape estimation means are outputted as position and shape feed back values to a plasma position and shape control means instead of the position and shape measured values. Since only a portion of the abnormal position and shape measured values may also be replaced with the position and shape estimation values, errors in the plasma position and shape feed back values can be reduced as a whole. In addition, even if the position and shape measured values are abnormal or if they can not be measured, plasma control can be continued by alternative position and shape estimation values, thereby enabling to avoid interruption of plasma control. Since the position and shape estimation values are obtained not only with the measured values of coil current but also with the position and shape estimation values, the accuracy is improved. Further, noises superposed on the position and shape measured values are filtered, and the device is stabilized compared with a prior art device. (N.H.)

Plasma-chemical processes and systems

International Nuclear Information System (INIS)

Castro B, J.

1987-01-01

The direct applications of plasma technology on chemistry and metallurgy are presented. The physical fundaments of chemically active non-equilibrium plasma, the reaction kinetics, and the physical chemical transformations occuring in the electrical discharges, which are applied in the industry, are analysed. Some plasma chemical systems and processes related to the energy of hydrogen, with the chemical technology and with the metallurgy are described. Emphasis is given to the optimization of the energy effectiveness of these processes to obtain reducers and artificial energetic carriers. (M.C.K.) [pt

Plasma technology for treatment of waste

Energy Technology Data Exchange (ETDEWEB)

Cohn, D [Massachusetts Inst. of Technology, Cambridge, MA (United States). Plasma Fusion Center

1997-12-31

Meeting goals for waste cleanup will require new technology with improved environmental attractiveness and reduced cost. Plasma technology appears promising because of the high degree of controllability; capability to process waste without the adverse effects of combustion; and a very wide temperature range of operation. At the Plasma Fusion Center at the Massachusetts Institute of Technology, a range of plasma technologies are being investigated. `Hot` thermal plasmas produced by DC arc technology are being examined for treatment of solid waste. In conjunction with this activity, new diagnostics are being developed for monitoring arc furnace operating parameters and gaseous emissions. Electron-beam generated plasma technology is being investigated as a means of producing non-thermal `cold` plasmas for selective processing of dilute concentrations of gaseous waste. (author). 4 figs., 5 refs.

Plasma apolipoprotein M is reduced in metabolic syndrome but does not predict intima media thickness

DEFF Research Database (Denmark)

Dullaart, Robin P F; Plomgaard, Peter; de Vries, Rindert

2009-01-01

BACKGROUND: Apolipoprotein (apo) M may exert anti-atherogenic properties in experimental studies. Its hepatic gene expression may be linked to glucose and lipid metabolism. Plasma apoM is decreased in obese mouse models. We hypothesized that plasma apoM is lower in metabolic syndrome (Met...

Low plasma volume coincides with sympathetic hyperactivity and reduced baroreflex sensitivity in formerly preeclamptic patients.