Sample records for amp prolongs graft

  1. Cyclic AMP system in muscle tissue during prolonged hypokinesia (United States)

    Antipenko, Y. A.; Bubeyev, Y. A.; Korovkin, B. F.; Mikhaleva, N. P.


    Components of the cyclic Adenosine-cyclic-35-monophosphate (AMP) system in the muscle tissue of white rats were studied during 70-75 days of hypokinesia, created by placing the animals in small booths which restricted their movements, and during the readaptation period. In the initial period, cyclic AMP levels and the activities of phosphodiesterase and adenylate cyclase in muscle tissue were increased. The values for these indices were roughly equal for controls and experimental animals during the adaptation period, but on the 70th day of the experiment cAMP levels dropped, phosphodiesterase activity increased, and the stimulative effect of epinephrine on the activity of adenylate cyclase decreased. The indices under study normalized during the readaptation period.

  2. Prolonging warm ischemia reduces the cold preservation limits of liver grafts in swine

    Institute of Scientific and Technical Information of China (English)

    De-Ke Qing


    BACKGROUND:The critical shortage of transplantable organs necessitates utilization of unconventional donors. But the safe time limits of cold preservation of liver grafts subjected to warm ischemia (WI) for up to 30 minutes from non-heart-beating-donors (NHBDs) has not been delineated. In this study, we investigated how the limits of cold ischemia (CI) in University of Wisconsin (UW) solution are changed in liver grafts subjected to WI from 10 to 30 minutes. METHODS:A simple porcine NHBD liver transplantation (LT) model was developed. In donors, livers were subjected to 10, 20 or 30 minutes of WI and subsequent different times of CI in UW solution. Animals were divided into three groups (WI 10 min, WI 20 min, WI 30 min, n=13 in each group) and nine subgroups (from CI 6 h to CI 28 h). One-week survival rates of recipients, hepatic function, liver energy metabolism, grafted liver microcirculation and pathological observations of the liver were compared. RESULTS:In the WI 10 min group, the one-week survival rate of the CI 20 h subgroup was signiifcantly higher than in the other two subgroups (CI 24 h and CI 28 h) (P CONCLUSIONS: The cold preservation limits of the liver grafts shortened from 20 to 12 to 6 hours when WI time was prolonged from 10 to 20 to 30 minutes. Only the liver grafts within these time limits could be safely transplanted.

  3. FTY720 treatment prolongs skin graft survival in a completely incompatible strain combination. (United States)

    Lima, R S M; Nogueira-Martins, M F; Silva, H T; Pestana, J O M; Bueno, V


    FTY720 has shown potent immunomodulatory activity in a variety of animal organ transplant models. However, the in vivo immunosuppressive mechanism of FTY720 is still not fully understood. It has been suggested that the marked decrease in the number of peripheral blood lymphocytes during FTY720 administration could be responsible for its immunosuppressive effects. Our aims were: (1) to study the effects of FTY720 treatment on skin graft survival using a fully mismatched strain combination and (2) to evaluate lymphocyte numbers in different sites at 5 days after skin transplant. C57BL/6 mice and BALB/c mice were the donors and recipients respectively. BALB/c mice received FTY720 (1 mg/kg/d) orally for 4 consecutive days. Drug administration started 1 day before skin transplants. A small segment of tail skin was affixed on the right dorsal side of the mouse via sutures. The administration of FTY720 (4 mg/kg) prolonged skin graft survival from 12.6 +/- 2.2 days (no treatment) to 16.6 +/- 4.2 days. The histologic findings of rejection were similar for all groups. Five days after transplant, lymphocyte numbers were significantly increased in lymph nodes compared with nontransplanted or isogenic graft mice. FTY720 decreased lymphocyte numbers only in the spleen. In conclusion, FTY720 prolonged skin graft survival in a fully mismatched strain combination when administered for 4 days (day -1 to day +2) at a dose of 1 mg/kg/d. The decreased number of lymphocytes in the spleen suggests that the spleen may be a target of FTY720 activity, during the early posttransplant period.

  4. Study of the prolonged release of theopylline from polymeric matrices based on grafted chitosan with acrylamide. (United States)

    Tapia, C; Costa, E; Terraza, C; Munita, A M; Yazdani-Pedram, M


    The aim of this work was to study the performance of chitosan (CB) grafted with acrylamide (CB-g-A) as prolonged drug release matrix as compared with unmodified chitosan. A non-pH dependent swelling behaviour for the matrix tablets based on grafted chitosan was observed. The overlaping between degree of swelling measured by weighing (DSw) and measured by increase of diameter (DSd) up to 240 minutes showed that the swelling process could be isotropic. The non-pH dependent swelling behaviour of these matrices could be explained by the partial substitution of amine groups of the chitosan chain by acrylamide. The grafting reaction provides an ionizable amine group by a neutral amide group which make the matrix non pH-dependent. On the contrary, the matrix tablet based on chitosan showed a pH dependent swelling behaviour where the swelling process could be anisotropic. The higher degree of erosion and swelling of the formulation based on CB-g-A600 (%G = 600) compared with the formulation based on chitosan and CB-g-A418 (%G = 418) could explain the higher fraction of theopylline released. For all formulations studied in this work, the amount of theopylline released from the matrix tablets was found to be controlled by a combination of the diffusion process and relaxation of the polymeric structure. These results match with the controlled swelling behaviour and low degree of erosion observed for these systems.

  5. Prolonged AICAR-induced AMP-kinase activation promotes energy dissipation in white adipocytes: novel mechanisms integrating HSL and ATGL. (United States)

    Gaidhu, Mandeep P; Fediuc, Sergiu; Anthony, Nicole M; So, Mandy; Mirpourian, Mani; Perry, Robert L S; Ceddia, Rolando B


    This study was designed to investigate the effects of prolonged activation of AMP-activated protein kinase (AMPK) on lipid partitioning and the potential molecular mechanisms involved in these processes in white adipose tissue (WAT). Rat epididymal adipocytes were incubated with 5'-aminoimidasole-4-carboxamide-1-beta-d-ribofuranoside (AICAR;0.5 mM) for 15 h. Also, epididymal adipocytes were isolated 15 h after AICAR was injected (i.p. 0.7 g/kg body weight) in rats. Adipocytes were utilized for various metabolic assays and for determination of gene expression and protein content. Time-dependent in vivo plasma NEFA concentrations were determined. AICAR treatment significantly increased AMPK activation, inhibited lipogenesis, and increased FA oxidation. This was accompanied by upregulation of peroxisome proliferator-activated receptor (PPAR)alpha, PPARdelta, and PPARgamma-coactivator-1alpha (PGC-1alpha) mRNA levels. Lipolysis was first suppressed, but then increased, both in vitro and in vivo, with prolonged AICAR treatment. Exposure to AICAR increased adipose triglyceride lipase (ATGL) content and FA release, despite inhibition of basal and epinephrine-stimulated hormone-sensitive lipase (HSL) activity. Here, we provide evidence that prolonged AICAR-induced AMPK activation can remodel adipocyte metabolism by upregulating pathways that favor energy dissipation versus lipid storage in WAT. Additionally, we show novel time-dependent effects of AICAR-induced AMPK activation on lipolysis, which involves antagonistic modulation of HSL and ATGL.

  6. Overexpression of thioredoxin in islets transduced by a lentiviral vector prolongs graft survival in autoimmune diabetic NOD mice

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    Sytwu Huey-Kang


    Full Text Available Abstract Pancreatic islet transplantation is considered an appropriate treatment to achieve insulin independence in type I diabetic patients. However, islet isolation and transplantation-induced oxidative stress and autoimmune-mediated destruction are still the major obstacles to the long-term survival of graft islets in this potential therapy. To protect islet grafts from inflammatory damage and prolong their survival, we transduced islets with an antioxidative gene thioredoxin (TRX using a lentiviral vector before transplantation. We hypothesized that the overexpression of TRX in islets would prolong islet graft survival when transplanted into diabetic non-obese diabetic (NOD mice. Methods Islets were isolated from NOD mice and transduced with lentivirus carrying TRX (Lt-TRX or enhanced green fluorescence protein (Lt-eGFP, respectively. Transduced islets were transplanted under the left kidney capsule of female diabetic NOD mice, and blood glucose concentration was monitored daily after transplantation. The histology of the islet graft was assessed at the end of the study. The protective effect of TRX on islets was investigated. Results The lentiviral vector effectively transduced islets without altering the glucose-stimulating insulin-secretory function of islets. Overexpression of TRX in islets reduced hydrogen peroxide-induced cytotoxicity in vitro. After transplantation into diabetic NOD mice, euglycemia was maintained for significantly longer in Lt-TRX-transduced islets than in Lt-eGFP-transduced islets; the mean graft survival was 18 vs. 6.5 days (n = 9 and 10, respectively, p Conclusion We successfully transduced the TRX gene into islets and demonstrated that these genetically modified grafts are resistant to inflammatory insult and survived longer in diabetic recipients. Our results further support the concept that the reactive oxygen species (ROS scavenger and antiapoptotic functions of TRX are critical to islet survival after

  7. Inhibition of a cAMP-dependent Ca-activated K conductance by forskolin prolongs Ca action potential duration in lamprey sensory neurons. (United States)

    Womble, M D; Wickelgren, W O


    Intracellular recordings from primary mechanosensory neurons (dorsal cells) of the lamprey spinal cord were made to test the membrane effects of forskolin, an activator of adenylate cyclase in these cells. At a concentration of 50 microM, forskolin was found to have a pronounced broadening effect on calcium action potentials (Ca APs) produced in the presence of voltage-activated K channel blockers (TEA, 3,4-DAP). Forskolin had no effect on passive membrane properties of the cells, such as resting potential or input resistance. Nor did it affect delayed rectification or Na APs and thus appeared not to block voltage-activated K channels. Forskolin's effect was evident only when a significant Ca component to the AP was present. It appeared not to increase the conductance of the Ca channel since its action was accompanied by a decrease in membrane conductance during the Ca AP, indicating instead an inhibition of a repolarizing Ca-activated conductance, other than a Ca-activated Cl conductance. The prolongation of Ca APs by forskolin, barium or the neurotransmitter GABA were all correlated in voltage-clamp with a decrease in outward current. Under the conductions used here, the major outward conductance in dorsal cells is a Ca-activated K conductance (gK(Ca]28, and it is concluded that the most probable mode of action for forskolin is via a cyclic AMP-mediated inhibition of this conductance. GABA has also been shown to prolong Ca APs in lamprey dorsal cells by inhibiting a repolarizing gK(Ca)28. Thus, the action of this transmitter may be mediated by an increase in intracellular cyclic AMP.

  8. Recombinant IL-33 prolongs leflunomide-mediated graft survival by reducing IFN-γ and expanding CD4(+)Foxp3(+) T cells in concordant heart transplantation. (United States)

    Dai, Chen; Lu, Fang-Na; Jin, Ning; Yang, Bo; Gao, Chang; Zhao, Bin; Fu, Jia-Zhao; Hong, Shi-Fu; Liang, Han-Ting; Chen, Li-Hong; Chen, Zhi-Shui; Chen, Jie; Qi, Zhong-Quan


    Interleukin (IL)-33 is a novel IL-1 family member, and its administration has been associated with promotion of T helper type-2 (Th2) cell activity and cytokines, particularly IL-4 and IL-5 in vivo. Recently, IL-33 was shown to increase CD4(+)Foxp3(+) regulatory T cells (Tregs) and to suppress levels of the Th1-type cytokine IFN-γ in allogeneic heart transplantation in mice. Therefore, we hypothesized that IL-33 and leflunomide (Lef) could prolong graft survival in the concordant mouse-to-rat heart transplantation model. In this model, xenografts undergo acute humoral xenograft rejection (AHXR) typically on day 3 or cell-mediated rejection approximately on day 7 if AHXR is inhibited by Lef treatment. Recipients were treated with Lef (n=6), IL-33 (n=6), IL-33 combined with Lef (n=6), or left untreated (n=6) for survival studies. Heart grafts were monitored until they stopped beating. Mouse heterotopic grafts were performed, and recipients were sacrificed on days 2 and 7 for histological and flow cytometric analyses. The combination of IL-33 and Lef significantly prolonged the grafts from 17.3±2.3 to 2.8±0.4 days, compared to untreated controls. IL-33 administration with Lef, while facilitating Th2-associated cytokines (IL-4 on day 2 but not day 7), also decreased IFN-γ on day 2 and day 7, compared with Lef treatment only. Furthermore, IL-33 with Lef administration caused an expansion of suppressive CD4(+)Foxp3(+) Tregs in rats. The IL-33 and Lef combination therapy resulted in significantly prolonged graft survival, associated with markedly decreased Th1 cells and increased IL-10 levels. In addition, the combination therapy significantly decreased the percentage of CD-45(+) B cells on days 2 and 7, compared with monotherapy. These findings reveal a new immunoregulatory property of IL-33. Specifically, it facilitates regulatory cells, particularly functional CD4(+)Foxp3(+) Tregs that underlie IL-33-mediated cardiac xenograft survival. Moreover, it can decrease Th

  9. Synthesis and Properties of Sepiolite Grafted P(AMPS-co-AM) Superabsorbent Resin%海泡石接枝P(AMPS-co-AM)高吸水树脂的合成及性能

    Institute of Scientific and Technical Information of China (English)

    徐继红; 谭德新; 李忠; 颜凌燕


    Sepiolite( ST) grafted poly(2-acrylamido-2-methylpropanesulfonic acid-co-acrylamide) high-salt superabsorbent resin was synthesized through microwave irradiation,using sepiolite, 2-acrylamido-2-methylpropanesulfonic acid ( AMPS ) and acrylamide ( AM ) as raw materials. The effects of the concentration of inorganic salt solution, kind of various metal ions and amount of ST on water absorbency of the superabsorbent resin were studied. The ratio of liquid absorption and water-retention properties of the superabsorbent resin were also studied. Meanwhile, the microstructure of resin was characterized by means of FTIR,XRD and SEM. The results indicate that the water absorbency of the superabsorbent resin decreases with increasing concentration of various external saline solutions, and has the following tendency in different metal ions saline solutions: NaCl > CaCl2 > FeCl3, and that the water absorption capacity of the superabsorbent resin could be remarkably enhanced by introducing a proper amount of ST. And the superabsorbent resin has a high water absorption rate and good water retention properties. FTIR and XRD characterization indicates that the grafting copolymerization reaction occurred between ST and the organic monomer. Some of the monomers were inserted into the interlamination of ST and intercalation was formed in the superabsorbent resin. SEM shows that the resin had microporous and laminate structure.%以2-丙烯酰胺基-2-甲基丙磺酸(AMPS)、丙烯酰胺(AM)和海泡石黏土(ST)为原料,采用微波辐射方法制备了ST接枝P(AMPS-co-AM)耐盐性高吸水性树脂,考察了海泡石用量、无机盐溶液金属离子价态和浓度对树脂吸水倍率的影响,研究了树脂的吸水速率和保水性能.用FTIR、XRD、SEM对吸水性树脂进行了表征.结果表明,树脂的吸水倍率随着无机盐溶液浓度的增加而减小,在不同价态金属离子盐溶液中,树脂的吸水倍率顺序为NaCl> CaCl2>FeCl3,在体系中适量

  10. Repeated intrathecal administration of plasmid DNA complexed with polyethylene glycol-grafted polyethylenimine led to prolonged transgene expression in the spinal cord. (United States)

    Shi, L; Tang, G P; Gao, S J; Ma, Y X; Liu, B H; Li, Y; Zeng, J M; Ng, Y K; Leong, K W; Wang, S


    Gene delivery into the spinal cord provides a potential approach to the treatment of spinal cord traumatic injury, amyotrophic lateral sclerosis, and spinal muscular atrophy. These disorders progress over long periods of time, necessitating a stable expression of functional genes at therapeutic levels for months or years. We investigated in this study the feasibility of achieving prolonged transgene expression in the rat spinal cord through repeated intrathecal administration of plasmid DNA complexed with 25 kDa polyethylenimine (PEI) into the lumbar subarachnoid space. With a single injection, DNA/PEI complexes could provide transgene expression in the spinal cord 40-fold higher than naked plasmid DNA. The transgene expression at the initial level persisted for about 5 days, with a low-level expression being detectable for at least 8 weeks. When repeated dosing was tested, a 70% attenuation of gene expression was observed following reinjection at a 2-week interval. This attenuation was associated with apoptotic cell death and detected even using complexes containing a noncoding DNA that did not mediate any gene expression. When each component of the complexes, PEI polymer or naked DNA alone, were tested in the first dosing, no reduction was found. Using polyethylene glycol (PEG)-grafted PEI for DNA complexes, no attenuation of gene expression was detected after repeated intrathecal injections, even in those rats receiving three doses, administered 2 weeks apart. Lumbar puncture is a routine and relatively nontraumatic clinical procedure. Repeated administration of DNA complexed with PEG-grafted PEI through this less invasive route may prolong the time span of transgene expression when needed, providing a viable strategy for the gene therapy of spinal cord disorders.

  11. Pregnancy estrogen drives the changes of T-lymphocyte subsets and cytokines and prolongs the survival of H-Y skin graft in murine model

    Institute of Scientific and Technical Information of China (English)

    LIN Xing-guang; ZHOU Qi; WANG Li; GAO Ying; ZHANG Wei-na; LUO Zhen-long; CHEN Bi-cheng; CHEN Zhong-hua; CHANG Sheng


    Background Estrogen as well as CD4+Foxp3+ regulatory T cells were shown to have a protective role not only in maintaining maternal-fetal tolerance but also against autoimmune diseases. We aimed to investigate whether the pregnancy levels of estrogen are enough to induce transplant tolerance as to maintain fetal-maternal tolerance.Methods We established H-Y skin graft transplantation in C57BL/6 ovariectomized mice that reconstituted with estrogen. Subsequently, consecutive daily estrogen injection was administrated. Tregs and the cytokines in the peripheral blood were detected by flow cytometry and ELISA pre- and post-transplant.Results The results indicated that pregnancy levels of estrogen could promote Tregs in secondary lymphoid organs and peripheral blood (P0.05). The estrogen-treated recipients accepted H-Y skin grafts for more than 35 days (median survival time (MST): (44.0±1.2) days) compared with estrogen-untreated mice (MST:(23.0±1.6) days) (P <0.05). It was also observed that estrogen up-regulated the expression of Foxp3, but did not affect CD3+CD8+ effector T-cells in non-transplant mice. While in the presence of H-Y antigens, the expression of Foxp3 was more significant and CD3+CD8+ effector T cells were decreased significantly (P <0.05). Meanwhile, the up-regulated IL-10 and IL-4, and down-regulated IFN-Y could be observed (P <0.05).Conclusions Pregnancy levels of estrogen may promote the conversion of peripheral Tregs in secondary lymphoid organs, but show no effect on the natural Tregs production, differentiation and maturity in central lymphoid organs.Furthermore, pregnancy levels of estrogen could significantly prolong the survivals of H-Y skin grafts by the expansion of Tregs, suppression of CD3+CD8+ effector T-cells and immune shift towards Th2 cytokines.

  12. 应用两步接枝法制备新型改性聚丙烯滤嘴材料%A novel filtration of cigarette smoke prepared by two steps grafting of AA and AMPS monomer onto PP matrix

    Institute of Scientific and Technical Information of China (English)

    王海涛; 魏俊富; 王翱; 陈远; 赵禹; 杨闯


    In order to improve the poor adsorption for cigarette smoke and tar of polypropylene (PP) fiber, AA and AMPS were grafted onto PP fiber matrix by two steps plasma irradiation grafting for preparation a novel composite filtration of cigarette smoke PP-g-(AA + AMPS). The factors influenced the grafting degree were discussed, such as the irradiation time, concentration of monomer and the concentration of inhibitor. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FT-IR) and scanning electron microscopy (SEM) were used to characterize the chemical and morphological changes of the original and grafted PP fiber matrix, the results indicated that AMPS was grafted onto the surface of PP fiber matrix. The results indicated that the filtration efficiency of PP fiber was improved significant after graft modification, the total particulate matter in mainstream cigarette smoke reduces 30. 5%, and the concentration of tar and nicotine are decrease 43. 2% and 31. 7% , respectively.%为了解决烟用聚丙烯(PP)滤嘴材料对烟气吸附性能差、降焦性能低等问题,采用等离子体辐射引发的方法,在烟用聚丙烯纤维基体上分两步接枝丙烯酸(AA)和2-丙烯酰胺-2-甲基丙磺酸(AMPS)单体,制备了聚丙烯高吸附滤嘴.讨论了单体浓度、辐照时间、阻聚剂浓度对聚丙烯纤维接枝率的影响.利用衰减全反射红外光谱和扫描电子显微镜对接枝后的聚丙烯纤维基体的表面化学组成和形貌结构进行表征,结果表明,AMPS单体被成功接枝到PP纤维上.当改性后聚丙烯纤维的接枝率为22.8%时,改性后聚丙烯纤维滤嘴对烟气的过滤效果比改性前明显提高,烟气中的总粒相物比未改性滤嘴降低了30.5%,焦油及烟碱含量分别降低43.2%和31.7%.

  13. Nature of the suppressor cells mediating prolonged graft survival after administration of extracted histocompatibility antigen and cyclosporine

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    Yoshimura, N.; Kahan, B.D.


    Antigen-specific suppressor T cells are induced by donor histocompatibility antigen extracted from spleen cells with 3M KCl combined with cyclosporine (Ag-CsA). A single i.v. injection of 5 mg 3M-KCl-extracted donor Buffalo (Buf, RT1b) antigen (Ag) combined with a three day course of CsA prolonged renal allograft survival in Wistar-Furth (WFu, RT1u) hosts to a greater extent (MST 26.5 days) than CsA alone (MST 11.8 days). Peripheral blood lymphocytes (PBL) or spleen cells harvested from Ag-CsA-treated recipients ten days after transplantation inhibited the mixed lymphocyte reaction (MLR) between normal responder WFu cells and irradiated Buf cells (55.6% and 64.4% suppression, respectively, P less than 0.025), but not third-party Brown-Norway (BN, RT1n) stimulator cells (13.6% and -18.3% suppression, respectively, NS). The suppressor effect was not mediated by cytolytic cells; there was neither primary nor secondary cytolytic activity against /sup 51/Cr-labeled Con-A blastoid Buf cells. The suppressor cells were neither adherent to plastic dishes nor to nylon-wool columns. PBL irradiated with 800 rads, but not 1500 rads, suppressed the MLR. A single injection of cyclophosphamide (CY, 25 mg/kg) seven days after transplantation abrogated the suppression induced by Ag-CsA treatment. Moreover, PBL from Ag-CsA recipients failed to suppress the MLR, if depleted either of all T cells by treatment with monoclonal antibody (Mab) W3/13 HLK (pan T cells; % suppression -15.8), or of cytotoxic/suppressor cells with Mab OX-8 (-19.3% suppression) together with rabbit antimouse immunoglobulin and complement.

  14. 微波辐射CMC接枝AA/AMPS高吸水树脂的制备%Study on Synthesis of CMC Grafted AA/AMPS Super Absorbent Resin by Microwave Irradiation

    Institute of Scientific and Technical Information of China (English)

    徐继红; 陶俊; 谭德新; 熊现秋


    Carboxymethylcellulose (CMC) grafted acrylic acid (AA)/2 - acrylamido -2 -methyl propane sulfonic acid ( AMPS) superabsorbent resin was synthesized by microwave irradiation and characterized by use of FT - IR. The impact factors on water absorption of resin, such as the amount of crosslinker, the a-mount of initiator, the ratio of monomers, neutralization degree and microwave power, were discussed. The results showed that the water absorption rate of resin was 690 g/g in distilled water and 90 g/g in normal saline respectively under the optimum conditions. The results of FT - IR characterization showed that AA and AMPS were grafted onto the molecule chain of CMC.%采用微波辐射方法制备了羧甲基纤维素钠(CMC)接枝丙烯酸(AA)/2-丙烯酰胺基-2-甲基丙磺酸(AMPS)高吸水性树脂,并用红外光谱对树脂进行了表征.探讨了交联剂用量、引发剂用量、单体配比、中和度和微波功率对树脂吸水性能的影响.实验结果表明:最佳合成条件下制备的高吸水性树脂吸蒸馏水倍率达690 g/g,吸生理盐水倍率为90 g/g;红外光谱分析表明:丙烯酸和2-丙烯酰胺基-2-甲基丙磺酸接枝到羧甲基纤维素钠分子链上.

  15. Prolonged in vivo administration of testosterone-enanthate, the widely used and abused anabolic androgenic steroid, disturbs prolactin and cAMP signaling in Leydig cells of adult rats. (United States)

    Bjelic, Maja M; Stojkov, Natasa J; Radovic, Sava M; Baburski, Aleksandar Z; Janjic, Marija M; Kostic, Tatjana S; Andric, Silvana A


    This study was designed to systematically analyze and define the effects of 1-day, 2-weeks, 10-weeks intramuscular administration of testosterone-enanthate, widely used and abused anabolic androgenic steroid (AAS), on main regulators of steroidogenesis and steroidogenic genes expression in testosterone-producing Leydig cells of adult rats. The results showed that prolonged (10-weeks) intramuscular administration of testosterone-enanthate, in clinically relevant dose, significantly increased prolactin, but decreased Prlr2 and Gnrhr in pituitary of adult rat. The levels of testosterone, Insl3, cAMP and mitochondrial membrane potential of Leydig cells were significantly reduced. This was followed by decreased expression of some steroidogenic enzymes and regulatory proteins such as Lhcgr, Prlr1/2, Tspo, Star, Cyp11a1, Cyp17a1, Dax1. Oppositely, Hsd3b1/2, Hsd3b5, Hsd17b4, Ar, Arr19 increased. In the same cells, transcriptional milieu of cAMP signaling elements was disturbed with remarkable up-regulation of PRKA (the main regulator of steroidogenesis). Increased prolactin together with stimulated transcription of Jak2/Jak3 could account for increased Hsd3b1/2 and Hsd3b5 in Leydig cells following 10-weeks in vivo treatment with testosterone-enanthate. In vitro studies revealed that testosterone is capable to increase level of Prlr1, Prlr2, Hsd3b1/2, Hsd3b5 in Leydig cells. Accordingly, testosterone-induced changes in prolactin receptor signaling together with up-regulation of PRKA, Hsd3b1/2, Hsd3b5, Ar in Leydig cells, could be the possible mechanism that contribute to the establishment of a new adaptive response to maintain homeostasis and prevent loss of steroidogenic function. Presented data provide new molecular insights into the relationship between disturbed testosterone homeostasis and mammalian reproduction and are important in terms of wide use and abuse of AASs and human reproductive health.

  16. Stent graft placement for dysfunctional arteriovenous grafts

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    Jeon, Gyeong Sik [Dept. of Radiology, CHA Bundang Medical Center, College of Medicine, CHA University, Seongnam (Korea, Republic of); Shin, Byung Seok; Ohm, Joon Young; Ahn, Moon Sang [Chungnam National University Hospital, Daejeon (Korea, Republic of)


    This study aimed to evaluate the usefulness and outcomes of stent graft use in dysfunctional arteriovenous grafts. Eleven patients who underwent stent graft placement for a dysfunctional hemodialysis graft were included in this retrospective study. Expanded polytetrafluoroethylene covered stent grafts were placed at the venous anastomosis site in case of pseudoaneurysm, venous laceration, elastic recoil or residual restenosis despite the repeated angioplasty. The patency of the arteriovenous graft was evaluated using Kaplan-Meier analysis. Primary and secondary mean patency was 363 days and 741 days. Primary patency at 3, 6, and 12 months was 82%, 73%, and 32%, respectively. Secondary patency at the 3, 6, 12, 24, and 36 months was improved to 91%, 82%, 82%, 50%, and 25%, respectively. Fractures of the stent graft were observed in 2 patients, but had no effect on the patency. Stent graft placement in dysfunctional arteriovenous graft is useful and effective in prolonging graft patency.

  17. Does interventional therapy prolong the patency of hemodialysis fistulas and grafts?; Verlaengert die radiologisch-interventionelle Therapie die Shuntnutzungsdauer bei haemodialysepflichtigen Patienten?

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    Schaefer, P.J.; Mueller-Huelsbeck, S.; Schaefer, F.K.; Soehne, J.; Charalambous, N.; Heller, M.; Jahnke, T. [Abt. Radiologie, Universitaetsklinikum Schleswig Holstein, Campus Kiel (Germany)


    Purpose: To retrospectively evaluate procedural success and patency after endovascular treatment of acute dysfunctional hemodialysis fistulas and grafts in a non-preselected patient cohort. Materials and Methods: 185 angiographies of hemodialysis fistulas and grafts on the upper extremities were analyzed for 120 patients (53 male, 67 female; mean-age 63.1{+-}11.4, range 24-91). 70% (n=130) were native arteriovenous fistulas, 17% (n=31) were prosthetic grafts, and 13% (n=24) were non-specific. In total, 278 lesions requiring endovascular treatment were detected. 13% (n=35) of the lesions were located in the arterial inflow, 18% (n=49) in native arteriovenous anastomoses, 7% (n=19) in prosthetic grafts and 62% (n=171) in the venous outflow. The primary, secondary and cumulative patency after endovascular treatment was calculated. Results: In 51% (n=94) of the cases endovascular treatment could be performed, in 8% (n=14) no lesion requiring treatment was detected, and in 42% (n=77) intervention was not considered possible. In 45% (n=124) of the detected lesions endovascular treatment was successful, in 18% (n=51) the intervention failed, and in 37% (n=103) intervention was not considered possible. The complication rate was 5% (n=10). The primary, secondary, and cumulative patency rates for 50% of the hemodialysis fistulas and grafts after endovascular treatment were 65, 191, and 370 days, respectively. The results differed significantly from each other with p<0.05 in the logrank test and logrank trend test. (orig.)

  18. Biocompatibility of polypropylene non-woven fabric membrane via UV-induced graft polymerization of 2-acrylamido-2-methylpropane sulfonic acid

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    Song Lingjie [State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Zhao Jie; Yang Huawei; Jin Jing; Li Xiaomeng [State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Stagnaro, Paola [Istituto per Io Studio delle Macromolecole, Consiglio Nazionale delle Ricerche, Via de Marini 6, 16149 Genova (Italy); Yin Jinghua, E-mail: [State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China)


    This work described the graft polymerization of a sulfonic acid terminated monomer, 2-acrylamido-2-methylpropane sulfonic acid (AMPS), onto the surface of polypropylene non-woven (NWF PP) membrane by O{sub 2} plasma pretreatment and UV-induced photografting method. The chemical structure and composition of the modified surfaces were analyzed by FTIR-ATR and XPS, respectively. The wettability was investigated by water contact angle and equilibrium water adsorption. And the biocompatibility of the modified NWF PP membranes was evaluated by protein adsorption and platelet adhesion. It was found that the graft density increased with prolonging UV irradiation time and increasing AMPS concentration; the water contact angles of the membranes decreased from 124{sup o} to 26{sup o} with the increasing grafting density of poly(AMPS) from 0 to 884.2 {mu}g cm{sup -2}, while the equilibrium water adsorption raised from 5 wt% to 75 wt%; the protein absorption was effectively suppressed with the introduction of poly(AMPS) even at the low grafting density (132.4 {mu}g cm{sup -2}); the number of platelets adhering to the modified membrane was dramatically reduced when compared with that on its virgin surface. These results indicated that surface modification of NWF PP membrane with AMPS was a facile approach to construct biocompatible surface.

  19. Waterborne Epoxy Resin Modified by AMPS

    Institute of Scientific and Technical Information of China (English)


    A stable epoxy emulsion was prepared with epoxy resin (EP) as raw material, 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) as modifier and benzoyl peroxide as initiator. By criterion of yield of the copolymer AMPS-EP, water-solubility, change of the acid value and intrinsic viscosity [η] along with reaction time, the copolymerization course was deduced. It is found that during the process, AMPS takes part in both the grafting copolymerization with epoxy principal chain and the ring-opening polyaddition with epoxy group. It is also discovered that the yield of AMPS-EP and water dispersing varies with reaction time. When it reaches 1.5 h,AMPS-EP can obtain good water-solubility; but the water-solubility will go bad gradually ifit exceeds 3.5 h.( )R spectrum analysis indicates that partial epoxy group partially remains and the others create sulfonic ester.

  20. Prolonged Negative Pressure Wound Therapy Followed by Split-Thickness Skin Graft Placement for Wide Dehiscence of Clamshell Incision After Bilateral Lung Transplantation: A Case Report. (United States)

    Suzuki, H; Watanabe, T; Okazaki, T; Notsuda, H; Niikawa, H; Matsuda, Y; Noda, M; Sakurada, A; Hoshikawa, Y; Aizawa, T; Miura, T; Okada, Y


    Clamshell incision is a standard approach for bilateral lung transplantation, providing a good operative field; however, once wide dehiscence occurs, its management is sometimes difficult because of intense immunosuppression and malnutrition of the recipient. A 22-year-old man with idiopathic pulmonary arterial hypertension underwent cadaveric bilateral lung transplantation through a clamshell incision using standard cardiopulmonary bypass. He developed wound dehiscence on postoperative day (POD) 20 that resulted in exposure of the bilateral fifth ribs and open pneumothorax. Considering the extreme malnutrition and emaciation of the recipient, we avoided initial closure of the dehiscence. After the debridement of necrotic tissue, negative pressure wound therapy was initiated on POD 25 and was continued for approximately 6 months with trafermin spray application. Eventually, the wound, including the fifth ribs, was completely covered with granulation tissue except for the wire tying the sternum. On POD 217, the patient underwent removal of the sternal wire followed by split-thickness skin grafting. His wound was successfully closed and he was discharged without activity limitation on POD 265.

  1. Mesenchymal stem cells promote liver regeneration and prolong survival in small-for-size liver grafts: involvement of C-Jun N-terminal kinase, cyclin D1, and NF-κB.

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    Weijie Wang

    Full Text Available BACKGROUND: The therapeutic potential of mesenchymal stem cells (MSCs has been highlighted recently for treatment of acute or chronic liver injury, by possibly differentiating into hepatocyte-like cells, reducing inflammation, and enhancing tissue repair. Despite recent progress, exact mechanisms of action are not clearly elucidated. In this study, we attempted to explore whether and how MSCs protected hepatocytes and stimulated allograft regeneration in small-for-size liver transplantation (SFSLT. METHODS: SFSLT model was established with a 30% partial liver transplantation (30PLT in rats. The differentiation potential and characteristics of bone marrow derived MSCs were explored in vitro. MSCs were infused transvenously immediately after graft implantation in therapy group. Expressions of apoptosis-, inflammatory-, anti-inflammatory-, and growth factor-related genes were measured by RT-PCR, activities of transcription factors AP-1 and NF-κB were analyzed by EMSA, and proliferative responses of the hepatic graft were evaluated by immunohistochemistry and western blot. RESULTS: MSCs were successfully induced into hepatocyte-like cells, osteoblasts and adipocytes in vitro. MSCs therapy could not only alleviate ischemia reperfusion injury and acute inflammation to promote liver regeneration, but also profoundly improve one week survival rate. It markedly up-regulated the mRNA expressions of HGF, Bcl-2, Bcl-XL, IL-6, IL-10, IP-10, and CXCR2, however, down-regulated TNF-α. Increased activities of AP-1 and NF-κB, as well as elevated expressions of p-c-Jun, cyclin D1, and proliferating cell nuclear antigen (PCNA, were also found in MSCs therapy group. CONCLUSION: These data suggest that MSCs therapy promotes hepatocyte proliferation and prolongs survival in SFSLT by reducing ischemia reperfusion injury and acute inflammation, and sustaining early increased expressions of c-Jun N-terminal Kinase, Cyclin D1, and NF-κB.

  2. 冠状动脉旁路移植术后ICU监护时间延长的危险因素%Predictive risk factors for prolonged stay in intensive care unit in patients undergoing coronary artery bypass grafting surgery

    Institute of Scientific and Technical Information of China (English)

    袁忠祥; 刘健


    Objective To describe the preoperative factors of prolonged intensive care unit length of stay after coronary artery bypass grafting. Methods From 1997 to 2009, 1318 patients underwent isolated CABG in our hospital. Retrospective analysis was performed on these cases. Univariate and multivariate analyses for preoperative risk factors were performed. Prolonged length of ICU stay was defined as initial admission to ICU exceeding 72 h. Results The mean age of patients ( 322women and 996 men) was (67.4±9.4) years. Of 1318 patients undergoing isolated CABG from 1997 to 2009, 205 experienced prolonged length of ICU stay. The length of ICU stay was (40.1 ± 22.5 ) hours and ( 122.6 ± 48.7 ) hours separately.Overall in-hospital mortality was higher among these 205 patients ( 13.7% vs. 1.2%, P <0.05 ). The overall mortality was 3.1%. In univariate analyses, there were statistically significant differences with respect to the percentage of CPB, total bypass time, cross-clamp time, number of distal anastomoses, use of pressor agent, use of intro-aortic balloon pump,time of ventilation and hospital mortality. The significant risk factors were age, NYHA class Ⅲ/Ⅳ, left ventricular ejection fraction(LVEF) <0.40, renal failure, cerebrovascular and/or peripheral vascular disease, chronic obstructive pulmonary disease, recent acute myocardial infarction, prior percutaneous coronary intervention, left main stenosi, three-vessels disease. The variables entered into the multivariate logistic regression were age, NYHA class Ⅲ/Ⅳ, LVEF <0.40, renal failure, chronic obstructive pulmonary disease, recent acute myocardial infarction, prior percutaneous coronary intervention, three-vessels disease. According to the outcome of multivariate logistic regression, we can conclude the model of probability forecast and create a new variable named Pre. The area under ROC curve of the new variable Pre was larger than other variables. Conclusion The main risk factors of prolonged ICU

  3. Preparation and Characteristics of Corn Straw-Co-AMPS-Co-AA Superabsorbent Hydrogel



    In this study, the corn straw after removing the lignin was grafted with 2-acrylamido-2-methylpropanesulfonic acid (AMPS) to prepare sulfonated cellulose. The grafting copolymerization between the sulfonated cellulose and acrylic acid (AA) was performed using potassium persulfate and N,N′-methylenebisacrylamide as the initiator and crosslinking agent, respectively, to prepare corn straw-co-AMPS-co-AA hydrogels. The structure and properties of the resulting hydrogels were characterized by Four...

  4. Synthesis and Characterization of Graft Copolymer of Dextran and 2-Acrylamido-2-methylpropane Sulphonic Acid

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    Venkanna Azmeera


    Full Text Available A novel biodegradable graft copolymer of dextran (Dx and 2-acrylamido-2-methyl-1-propane sulphonic acid (AMPS was synthesized by grafting poly-AMPS chains onto dextran backbone by free radical polymerization using ceric ammonium nitrate (CAN as an initiator. Different amounts of AMPS were used to synthesize four different grades of graft copolymers with different side chain lengths. These grafted polymers were characterized by elemental analysis, FTIR, 1HNMR, rheological technique, scanning electron microscopy (SEM, thermogravimetric analysis (TGA, and X-ray diffractometry (XRD. They exhibited efficient flocculation performance in kaolin suspension.


    Institute of Scientific and Technical Information of China (English)

    吴仁涛; 陶秀俊; 鲁敬荣; 朱振广


    为了探讨低粘聚阴离子纤维素(LV-PAC)接枝磺酸盐共聚物的耐温性能,以Ce4+为引发剂,研究了LV-PAC水溶液与2-丙烯酰胺-2-甲基丙烷磺酸(简称AMPS)接枝共聚反应的最适宜反应条件.以红外光谱对共聚物进行了表征,用DSC测定了共聚物的热稳定性.结果表明:在45℃下,当反应时间为3 h,引发剂Ce4+(2.8×10-3 mol.L-1)的用量为2mL,接枝单体AMPS(1.8 mo1.L-1)的用量为9mL时,LV-PAC接枝AMPS共聚反应的接枝效率为94.7%,接枝率为30.5%.DSC分析表明接枝后所得共聚物的热分解温度达到了389℃,比LV-PAC提高了48℃,说明通过接枝磺酸盐的方法可以有效地提高LV-PAC的耐热稳定性.

  6. Antimicrobial Peptides (AMPs

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    Mehrzad Sadredinamin


    Full Text Available Antimicrobial peptides (AMPs are extensive group of molecules that produced by variety tissues of invertebrate, plants, and animal species which play an important role in their immunity response. AMPs have different classifications such as; biosynthetic machines, biological sources, biological functions, molecular properties, covalent bonding patterns, three dimensional structures, and molecular targets.These molecules have multidimensional properties including antimicrobial activity, antiviral activity, antifungal activity, anti-parasite activity, biofilm control, antitumor activity, mitogens activity and linking innate to adaptive immunity that making them promising agents for therapeutic drugs. In spite of this advantage of AMPs, their clinical developments have some limitation for commercial development. But some of AMPs are under clinical trials for the therapeutic purpose such as diabetic foot ulcers, different bacterial infections and tissue damage. In this review, we emphasized on the source, structure, multidimensional properties, limitation and therapeutic applications of various antimicrobial peptides.

  7. Bone graft (United States)

    ... around the area. The bone graft can be held in place with pins, plates, or screws. Why ... Orthopaedic Surgery, San Francosco, CA. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the ...

  8. Anticonvulsant effect of AMP by direct activation of adenosine A1 receptor. (United States)

    Muzzi, Mirko; Coppi, Elisabetta; Pugliese, Anna Maria; Chiarugi, Alberto


    Purinergic neurotransmission mediated by adenosine (Ado) type 1 receptors (A1Rs) plays pivotal roles in negative modulation of epileptic seizures, and Ado is thought to be a key endogenous anticonvulsant. Recent evidence, however, indicates that AMP, the metabolic precursor of Ado, also activate A1Rs. Here, we evaluated the antiepileptic effects of AMP adopting in vitro and in vivo models of epilepsy. We report that AMP reversed the increase in population spike (PS) amplitude and the decrease in PS latency induced by a Mg(2+)-free extracellular solution in CA1 neurons of mouse hippocampal slices. The AMP effects were inhibited by the A1R antagonist DPCPX, but not prevented by inhibiting conversion of AMP into Ado, indicating that AMP inhibited per se sustained hippocampal excitatory neurotransmission by directly activating A1Rs. AMP also reduced seizure severity and mortality in a model of audiogenic convulsion. Of note, the anticonvulsant effects of AMP were potentiated by preventing its conversion into Ado and inhibited by DPCPX. When tested in a model of kainate-induced seizure, AMP prolonged latency of convulsions but had no effects on seizure severity and mortality. Data provide the first evidence that AMP is an endogenous anticonvulsant acting at A1Rs.

  9. [Dopplerometry at prolonged pregnancy]. (United States)

    Salii-Prenichi, L; Milchev, N; Markova, D; Apiosjan, Zh


    Prolonged pregnancy, associated with low amniotic fluid is a reason for the increase of fetal mortality and morbidity. There is no a define test at prolonged pregnancy which can determine which pregnancy are at a risk for adverse outcome and complications. Dopplerometry as a noninvasive method for examination of blood circulation, and especially a. cerebri media and a. umbilicalis can be used for the prediction of the outcome of prolonged pregnancy.

  10. [Prolonged acute pancreatitis after bone marrow transplantation]. (United States)

    De Singly, B; Simon, M; Bennani, J; Wittnebel, S; Zagadanski, A-M; Pacault, V; Gornet, J-M; Allez, M; Lémann, M


    Acute pancreatitis is not infrequent after allogenic marrow transplantation. Several causes can predispose to pancreatitis, including Graft-Versus-Host Disease (GVHD), a condition which is probably underestimated. In the literature, few description of pancreatic GVHD can be found. Pancreatic GVHD diagnosis can be difficult if pancreatic involvement occurs without other typical manifestations of GVHD. We report the case of a woman, 54 years old, suffering from prolonged, painful pancreatitis two months after allogenic bone marrow transplantation for acute myeloid leucemia. Pancreatic GVHD diagnosis was performed after five weeks on duodenal biopsies despite the absence of diarrheoa. The patient dramatically improved within few days on corticosteroids.

  11. Synthesis, characterization, and swelling behaviors of a pH-responsive CMC-g-poly(AA-co-AMPS) superabsorbent hydrogel



    New superabsorbent hydrogels were synthesized through free radical graft copolymerization of partially neutralized acrylic acid (AA) and 2-acrylamido-2-methylpropanesulfonic acid (AMPS) onto carboxymethyl cellulose (CMC) backbones. The structure and morphology of the synthesized superabsorbent hydrogels were characterized by Fourier transform infrared spectroscopy and scanning electron microscope. The effect of the molar ratio of AMPS to AA, the APS concentration, and the CMC content on ...

  12. Properties of Starch-Poly(acrylamide-co-2-acrylamido-2-methylpropanesulfonic acid) Graft Copolymers Prepared by Reactive Extrusion (United States)

    Graft copolymers of starch with acrylamide and 2-acrylamido-2-methylpropanesulfonic acid (AMPS) were prepared by reactive extrusion in a twin-screw extruder. The weight ratio of total monomer to starch was fixed at 1:3, while the molar fraction of AMPS in the monomer feed ranged from 0 to 0.119. Mon...

  13. Sleutelmag en amp

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    P. J. Rossouw


    Full Text Available As die Heidelbergse Kategismus (Sondag 31 handel oor die sleutels van die Koninkryk, dan word die betrokkenheid van die ampte slegs per implikasie veronderstel. Meer eksplisiet word die amp en sleutelmag in die Nederlandse Geloofsbelydenis gekoppel; “ons glo dat hierdie ware kerk ooreenkomstig die geestelike bestuurswyse wat ons Here ons in sy Woord geleer het, geregeer moet word... hulle (moet sorg dra dat die ware godsdiens onderhou (word, die ware leer orals versprei, die oortreders op geestelike wyse vermaan en in toom gehou (word... (N.G.B. art. 30 en: “Ons glo verder dat die regeerders van die kerk, al is dit nuttig en goed om onder mekaar ’n bepaalde orde tot instandhouding van die liggaam van die kerk in te stel en te handhaaf, tog noukeurig moet oppas om nie af te wyk van wat Christus, ons enigste Meester, vir ons ingestel het nie... Ons aanvaar derhalwe slegs wat kan dien om eendrag en eenheid te bewaar en te bevorder, en om alles in gehoorsaamheid van God te onderhou. Daarvoor is nodig die ban en alles wat daarmee saamhang, toegepas ooreenkomstig die Woord van God” (N.G.B. art. 32.

  14. Exhaustion from prolonged gambling

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    Fatimah Lateef


    Full Text Available Complaints of fatigue and physical exhaustion are frequently seen in the acute medical setting, especially amongst athletes, army recruits and persons involved in strenuous and exertional physical activities. Stress-induced exhaustion, on the other hand, is less often seen, but can present with very similar symptoms to physical exhaustion. Recently, three patients were seen at the Department of Emergency Medicine, presenting with exhaustion from prolonged involvement in gambling activities. The cases serve to highlight some of the physical consequences of prolonged gambling.

  15. Exhaustion from prolonged gambling

    Institute of Scientific and Technical Information of China (English)

    Fatimah Lateef


    Complaints of fatigue and physical exhaustion are frequently seen in the acute medical setting, especially amongst athletes, army recruits and persons involved in strenuous and exertional physical activities.Stress-induced exhaustion, on the other hand, is less often seen, but can present with very similar symptoms to physical exhaustion.Recently, three patients were seen at theDepartment ofEmergencyMedicine, presenting with exhaustion from prolonged involvement in gambling activities.The cases serve to highlight some of the physical consequences of prolonged gambling.

  16. Assisted Medical Procedures (AMP) Project (United States)

    National Aeronautics and Space Administration — Documentation and Development: The AMP was initially being developed as part the Advanced Integrated Clinical System (AICS)-Guided Medical Procedure System for the...

  17. Deciding about treatments that prolong life (United States)

    Palliative care - treatments that prolong life; Palliative care - life support; End-of-life-treatments that prolong life; Ventilator - treatments that prolong life; Respirator - treatments that prolong life; ...

  18. Prolonged labour : women's experiences


    Nystedt, Astrid


    Aim: The overall aim of this thesis was to illuminate, describe, and promote understanding of women’s experiences of prolonged labour. The thesis compromises four studies. Methods: Paper I describes a case-referent study that recruited women (n = 255) giving singleton live birth to their first child by spontaneous labour after more than 37 completed weeks’ pregnancy. Participants completed a questionnaire that investigated childbirth experiences, previous family relationships, and childhood e...

  19. Salbutamol delays human eosinophil apoptosis via a cAMP-dependent mechanism. (United States)

    Kankaanranta, Hannu; Parkkonen, Jouni; Ilmarinen-Salo, Pinja; Giembycz, Mark A; Moilanen, Eeva


    Eosinophils play a major role in asthma. One described mechanism leading to the impaired clearance of these cells from the lung is the delay in their programmed cell death (apoptosis). β(2)-Adrenoceptor agonists have been shown to prolong survival and delay apoptosis of eosinophils. The aim of the present study was to evaluate the mechanisms, especially the role of cAMP pathway, in the prolongation of human eosinophil survival by a selective β(2)-agonist salbutamol. Isolated human peripheral blood eosinophils were cultured in the absence or presence of a β(2)-agonist salbutamol and the indicated antagonists/inhibitors under sterile conditions. Apoptosis was measured by using the relative DNA fragmentation assay and Annexin-V binding. Salbutamol prolonged survival of human eosinophils and it was inhibited by a β-receptor antagonist propranolol and mimicked by cell-permeant cAMP analogues dibutyryl- and 8-bromo-cAMP. Pharmacological inhibitors of adenylyl cyclase (SQ-22,536) and protein kinase A (Rp-8-CPT-cAMPS) antagonized the effects of salbutamol. The survival-prolonging action of salbutamol was potentiated by a phosphodiesterase inhibitor rolipram (EC(50) for the salbutamol effect was 13.6 ± 4.0 and 8.1 ± 3.1 nM in the absence and presence of rolipram, respectively; p=0.0142, n=10). In contrast, inhibition of Ca(2+)-activated K(+)-channels by apamin, charybdotoxin, iberiotoxin or paxilline did not affect the ability of salbutamol to prolong eosinophil survival. Taken together, the present results suggest that salbutamol at clinically relevant concentrations decreases apoptosis in human eosinophils by activating the cannonical β(2)-receptor-adenylyl cyclase-cAMP-protein kinase A pathway.

  20. Bone grafting: An overview

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    D. O. Joshi


    Full Text Available Bone grafting is the process by which bone is transferred from a source (donor to site (recipient. Due to trauma from accidents by speedy vehicles, falling down from height or gunshot injury particularly in human being, acquired or developmental diseases like rickets, congenital defects like abnormal bone development, wearing out because of age and overuse; lead to bone loss and to replace the loss we need the bone grafting. Osteogenesis, osteoinduction, osteoconduction, mechanical supports are the four basic mechanisms of bone graft. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. An ideal bone graft material is biologically inert, source of osteogenic, act as a mechanical support, readily available, easily adaptable in terms of size, shape, length and replaced by the host bone. Except blood, bone is grafted with greater frequency. Bone graft indicated for variety of orthopedic abnormalities, comminuted fractures, delayed unions, non-unions, arthrodesis and osteomyelitis. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. By adopting different procedure of graft preservation its antigenicity can be minimized. The concept of bone banking for obtaining bone grafts and implants is very useful for clinical application. Absolute stability require for successful incorporation. Ideal bone graft must possess osteogenic, osteoinductive and osteocon-ductive properties. Cancellous bone graft is superior to cortical bone graft. Usually autologous cancellous bone graft are used as fresh grafts where as allografts are employed as an alloimplant. None of the available type of bone grafts possesses all these properties therefore, a single type of graft cannot be recomm-ended for all types of orthopedic abnormalities. Bone grafts and implants can be selected as per clinical problems, the equipments available and preference of

  1. Predictable risk factors and clinical courses for prolonged transient tachypnea of the newborn

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    Ji Young Chang


    Full Text Available Purpose : Transient tachypnea of the newborn (TTN is usually benign and improves within 72 hours. However, it can also progress to prolonged tachypnea over 72 hours, profound hypoxemia, respiratory failure, and even death. The aim of this study is to find predictable risk factors and describe the clinical courses and outcomes of prolonged TTN (PTTN. Methods : The medical records of 107 newborns, &amp;gt;35+0 weeks of gestational age with TTN, who were admitted to the NICU at Seoul Asan Medical Center from January 2001 to September 2007 were reviewed. They were divided into 2 groups based on duration of tachypnea. PTTN was defined as tachypnea ?#247;2 hours of age, and simple TTN (STTN as tachypnea &amp;lt;72 hours of age. We randomly selected 126 healthy-term newborns as controls. We evaluated neonatal and maternal demographic findings, and various clinical factors. Results : Fifty-five infants (51% with total TTN were PTTN. PTTN infants had grunting, tachypnea &amp;gt;90/min, FiO2 &amp;gt;0.4, and required ventilator care more frequently than STTN infants. PTTN had lower level of serum total protein and albumin than STTN. The independent predictable risk factors for PTTN were grunting, maximal respiration rate &amp;gt;90/min, and FiO2 &amp;gt;0.4 within 6 hours of life. Conclusion : When a newborn has grunting, respiration rate &amp;gt;90/min, and oxygen requirement &amp;gt;0.4 of FiO2 within 6 hours of life, the infant is at high risk of having persistent tachypnea ?#247;2 hours. We need further study to find the way to reduce PTTN.

  2. Pseudomonas aeruginosa β-lactamase induction requires two permeases, AmpG and AmpP

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    Schneper Lisa


    Full Text Available Abstract Background In Enterobacteriaceae, β-lactam antibiotic resistance involves murein recycling intermediates. Murein recycling is a complex process with discrete steps taking place in the periplasm and the cytoplasm. The AmpG permease is critical to this process as it transports N-acetylglucosamine anhydrous N-acetylmuramyl peptides across the inner membrane. In Pseudomonadaceae, this intrinsic mechanism remains to be elucidated. Since the mechanism involves two cellular compartments, the characterization of transporters is crucial to establish the link. Results Pseudomonas aeruginosa PAO1 has two ampG paralogs, PA4218 (ampP and PA4393 (ampG. Topology analysis using β-galactosidase and alkaline phosphatase fusions indicates ampP and ampG encode proteins which possess 10 and 14 transmembrane helices, respectively, that could potentially transport substrates. Both ampP and ampG are required for maximum expression of β-lactamase, but complementation and kinetic experiments suggest they act independently to play different roles. Mutation of ampG affects resistance to a subset of β-lactam antibiotics. Low-levels of β-lactamase induction occur independently of either ampP or ampG. Both ampG and ampP are the second members of two independent two-gene operons. Analysis of the ampG and ampP operon expression using β-galactosidase transcriptional fusions showed that in PAO1, ampG operon expression is β-lactam and ampR-independent, while ampP operon expression is β-lactam and ampR-dependent. β-lactam-dependent expression of the ampP operon and independent expression of the ampG operon is also dependent upon ampP. Conclusions In P. aeruginosa, β-lactamase induction occurs in at least three ways, induction at low β-lactam concentrations by an as yet uncharacterized pathway, at intermediate concentrations by an ampP and ampG dependent pathway, and at high concentrations where although both ampP and ampG play a role, ampG may be of greater

  3. Bone grafts in dentistry

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    Prasanna Kumar


    Full Text Available Bone grafts are used as a filler and scaffold to facilitate bone formation and promote wound healing. These grafts are bioresorbable and have no antigen-antibody reaction. These bone grafts act as a mineral reservoir which induces new bone formation.

  4. Olecranon bone graft: revisited. (United States)

    Mersa, Berkan; Ozcelik, Ismail Bulent; Kabakas, Fatih; Sacak, Bulent; Aydin, Atakan


    Autogenous bone grafts are frequently in use in the field of reconstructive upper extremity surgery. Cancellous bone grafts are applied to traumatic osseous defects, nonunions, defects after the resection of benign bone tumors, arthrodesis, and osteotomy procedures. Cancellous bone grafts do not only have benefits such as rapid revascularization, but they also have mechanical advantages. Despite the proximity to the primary surgical field, cancellous olecranon grafts have not gained the popularity they deserve in the field of reconstructive hand surgery. In this study, the properties, advantages, and technical details of harvesting cancellous olecranon grafts are discussed.

  5. [Graft reconstruction of flexor tendons]. (United States)

    Pauchard, N; Pedeutour, B; Dautel, G


    The improvement of primary flexor tendon repair has limited the indications of secondary repairs to neglected initial wound care and deficiencies in the surgical technique or rehabilitation. The surgical and rehabilitation care is complex and prolonged, requiring full cooperation of the patient. That is why the surgeon must evaluate patient's ability to integrate instructions and to comply with a long and demanding protocol. The functional needs of the patient are important in treatment decisions and the surgeon should not hesitate to use an appropriate surgical alternative (tenodesis, arthrodesis, tendon transfer, etc.). After a brief historical review, the authors discuss the indications, technical procedures and finally the results of one-stage and two-stage flexor tendon graft, which despite mixed results keep a real place in our current armamentarium.

  6. Study on biotribological properties of UHMWPE grafted with MPDSAH

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Yaling; Xiong, Dangsheng, E-mail:; Shao, Silong


    In order to prolong the service life of artificial joints, a zwitterion monomer of MPDSAH ((3-(methacryloylamino)propyl)dimethyl (3-sulfopropyl)ammonium hydroxide) was grafted onto ultra-high molecular weight polyethylene (UHMWPE) powders to construct a brush-like structure by UV irradiation, and then the grafted UHMWPE powders were hot pressed as the bulk materials. The wettability of bulk materials surface with different monomer concentrations was analyzed. The tribological properties of modified UHMWPE bulk materials were investigated under distilled water and saline by sliding against stainless steel ball. The measurement of Fourier-transform infrared (FT-IR) spectroscopy indicates that MPDSAH is successfully grafted onto the surface of UHMWPE powders by UV irradiation. The contact angles of modified UHMWPE are decreased and the surface wettability is effectively improved. The friction coefficient of the modified sample is lower than that of untreated UHMWPE in aqueous lubricants during a long-term friction. With the increase of monomer concentration, the wear rate of grafted UHMWPE decreases gradually in distilled water. The grafting hydrophilic macromolecule polymer is helpful to form a lubricating film of water, which leads to the improvement of the lubricity of UHMWPE. - Highlights: ► PMPDSAH brushes were grafted onto UHMWPE powders by UV radiation. ► Wettability of PMPDSAH-grafted UHMWPE bulk material is improved. ► UHMWPE grafted with PMPDSAH brushes shows lower friction coefficient and wear rate.

  7. 冠状动脉旁路移植术后患者延长机械通气时间的危险因素及近期临床结果分析%Predictors of prolonged mechanical ventilation and short-term outcomes after coronary artery bypass grafting

    Institute of Scientific and Technical Information of China (English)

    吴慧; 胡盛寿; 郑哲; 张海涛; 袁昕


    Objective To analyze the predictors of prolonged mechanical ventilation (PMV) after isolated coronary artery bypass grafting (CABG) and the effects of PMV on short-term outcomes. Methods A total of 4022 consecutive patients underwent isolated CABG from Jan 2006 to Dec 2008 were analyzed retrospectively. Univariate and multivariate Logistic regression analyses were performed to investigate the predictors,in-hospital mortality and morbidity of PMV. Results Average mechanical ventilation time was 19. 12 hours. Multivariate logistic regression revealed that age (OR = 1. 04,P < 0. 001),BMI (OR=0.96,P<0.001),hypertension (OR = 1. 30,P<0.001),angina (OR = l. 18,P=0.01),NYHA classes (OR = 1.20,P = 0.002),diseased coronary artery number (OR = 1.19,P = 0.03) ,blood transfusion (OR = 1. 97,P<0. 001),postoperative use of dopamine and/or dobutamine (OR = 1. 31 ,P<0.001),epinephrine ( OR = 2.06,P < 0.001) and norepinephrine (OR = 1.67,P < 0.001) were independent predictors of PMV. PMV was significantly related with in-hospital morbidity (OR =2. 10,95% CI: 1. 75-2. 51),major events (O5=6.70,95%CI: 3. 80-11.80),secondary events (OR = 1.28,95%CI: 1.02-1.61). Conclusions Old age,lower BMI,hypertension,frequent heart attacks,poor cardiac function,more diseased coronary arteries,more frequent use of blood transfusion and vasoactive drugs can increase the risk of PMV after CABG. And PMV is associated with poor short-term outcomes.%目的 分析冠状动脉旁路移植术(CABG)后患者延长机械通气(PMV)时间的危险因素及其对近期临床结果的影响.方法 回顾性分析阜外心血管病医院2006年1月1日至2008年12月31日行单纯CABG术的4022例患者,单因素及Logistic回归多因素分析影响患者PMV时间的术前、术中、术后的危险因素及PMV与住院期间并发症及其他事件的关系.结果 患者术后平均辅助通气(MV)时间19.12 h,中位数为13 h.年龄(OR=1.04,P<0.001)、BMi(OR=0.96,P <0.001)、高血压( OR=1.30,P<0.001)

  8. Genetic influence on prolonged gestation

    DEFF Research Database (Denmark)

    Laursen, Maja; Bille, Camilla; Olesen, Annette Wind;


    OBJECTIVE: The purpose of this study was to test a possible genetic component to prolonged gestation. STUDY DESIGN: The gestational duration of single, first pregnancies by both female and male twins was obtained by linking the Danish Twin Registry, The Danish Civil Registration System...... twin pairs, which indicates genetic effects. Biometric modeling suggested that genetic factors account for 23% to 30% of the liability to prolonged gestation. The difference in concordance rate between monozygotic and dizygotic male twin pairs was small, and the best fitting model indicated no genetic...... factors. CONCLUSION: Maternal genes influence prolonged gestation. However, a substantial paternal genetic influence through the fetus was not found....


    Institute of Scientific and Technical Information of China (English)

    ZHANG Liansheng; A.F.Johnson


    A novel radical grafting copolymerization process has been designed for water-soluble polymers which avoids the problems of conducting grafting reactions in highly viscous polymerization media.A variety of water-soluble graft copolymers having starch or dextran as the backbone chain with grafted side chains of polyacrylamide (-AM-),poly (acrylic acid) (-AA-),poly (acrylamide-co-acrylic acid) (-AM-NH4AA-) or poly (acrylamide-co-2-acrylamido-2-methyl-1-propanesulphinic acid)(-AM-AMPS-) have been synthesized in gel droplets using a ceric sulphate redox initiator,and their properties compared.The reaction conditions were optimized taking into account reaction kinetic data and the observed properties of the products produced under different reaction conditions.The effects of the ratios of [backbone]/[graft monomer],[AM]/[AA]/[AMPS],[Ce4+]/[S2O8=] and pH value on the reaction rate,conversion,grafting degree,grafted chain length and the product molecular weight have been investigated.


    Institute of Scientific and Technical Information of China (English)



    It had been observed that there was a close relationship between cyclic AMP and the motility, energy metabolism, capaeitation and acrosome reaction of spermatozoa. In this study a radio-immunoassay procedure for measuring cAMP concentration in sperm and

  11. Preparation and Characteristics of Corn Straw-Co-AMPS-Co-AA Superabsorbent Hydrogel

    Directory of Open Access Journals (Sweden)

    Wei-Min Cheng


    Full Text Available In this study, the corn straw after removing the lignin was grafted with 2-acrylamido-2-methylpropanesulfonic acid (AMPS to prepare sulfonated cellulose. The grafting copolymerization between the sulfonated cellulose and acrylic acid (AA was performed using potassium persulfate and N,N′-methylenebisacrylamide as the initiator and crosslinking agent, respectively, to prepare corn straw-co-AMPS-co-AA hydrogels. The structure and properties of the resulting hydrogels were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, thermogravimetric analysis, and dynamic rheometry. The effects of initiator, crosslinker, monomer neutralization degree, and temperature on the swelling ratio of the hydrogels were studied. The water retention, salt resistance, and recyclability of the corn straw-co-AMPS-co-AA hydrogels were also investigated. The optimum water absorptivity of the corn straw hydrogels was obtained at a polymerization temperature of 50 °C with 1.2% crosslinker, 1:7 ratio of the pretreated corn straw and AA, 2% initiator, and 50% neutralized AA.

  12. The critical roles of cyclic AMP/cyclic AMP-dependent protein kinase in platelet physiology

    Institute of Scientific and Technical Information of China (English)

    Rong YAN; Suping LI; Kesheng DAI


    Platelets are the primary players in both thrombosis and hemostasis.Cyclic AMP (cAMP) and cAMP-dependent protein kinase (PKA) are important signaling molecules in the regulation of platelet function,such as adhesion,aggregation,and secretion.Elevation of intracellular cAMP,which induces the activation of PKA,results in the inhibition of platelet function.Thus,tight control of the intracellular cAMP/PKA signaling pathway has great implications for platelet-dependent hemostasis and effective cardiovascular therapy.In this review,we summarize the PKA substrates and their contributions to platelet function,especially the advancing understanding of the cAMP/PKA-dependent signaling pathway in platelet physiology.In addition,we suggest the possibility that cAMP/PKA is involved in the platelet procoagulant process and receptor ectodomain shedding.

  13. Three Yersinia enterocolitica AmpD Homologs Participate in the Multi-Step Regulation of Chromosomal Cephalosporinase, AmpC. (United States)

    Liu, Chang; Wang, Xin; Chen, Yuhuang; Hao, Huijing; Li, Xu; Liang, Junrong; Duan, Ran; Li, Chuchu; Zhang, Jing; Shao, Shihe; Jing, Huaiqi


    In many gram negative bacilli, AmpD plays a key role in both cell well-recycling pathway and β-lactamase regulation, inactivation of the ampD causes the accumulation of 1,6-anhydromuropeptides, and results in the ampC overproduction. In Yersinia enterocolitica, the regulation of ampC expression may also rely on the ampR-ampC system, the role of AmpD in this species is still unknown. In this study, three AmpD homologs (AmpD1, AmpD2, and AmpD3) have been identified in complete sequence of strain Y. enterocolitica subsp. palearctica 105.5R(r). To understand the role of three AmpD homologs, several mutant strains were constructed and analyzed where a rare ampC regulation mechanism was observed: low-effective ampD2 and ampD3 cooperate with the high-effective ampD1 in the three levels regulation of ampC expression. Enterobacteriaceae was used to be supposed to regulate ampC expression by two steps, three steps regulation was only observed in Pseudomonas aeruginosa. In this study, we first reported that Enterobacteriaceae Y. enterocolitica can also possess a three steps stepwise regulation mechanism, regulating the ampC expression precisely.

  14. Percutaneous treatment of complications occurring during hemodialysis graft recanalization

    Energy Technology Data Exchange (ETDEWEB)

    Sofocleous, Constantinos T. E-mail:; Schur, Israel; Koh, Elsie; Hinrichs, Clay; Cooper, Stanley G.; Welber, Adam; Brountzos, Elias; Kelekis, Dimitris


    Introduction/objective: To describe and evaluate percutaneous treatment methods of complications occurring during recanalization of thrombosed hemodialysis access grafts. Methods and materials: A retrospective review of 579 thrombosed hemodialysis access grafts revealed 48 complications occurring during urokinase thrombolysis (512) or mechanical thrombectomy (67). These include 12 venous or venous anastomotic ruptures not controlled by balloon tamponade, eight arterial emboli, 12 graft extravasations, seven small hematomas, four intragraft pseudointimal 'dissections', two incidents of pulmonary edema, one episode of intestinal angina, one procedural death, and one distant hematoma. Results: Twelve cases of post angioplasty ruptures were treated with uncovered stents of which 10 resulted in graft salvage allowing successful hemodialysis. All arterial emboli were retrieved by Fogarty or embolectomy balloons. The 10/12 graft extravasations were successfully treated by digital compression while the procedure was completed and the graft flow was restored. Dissections were treated with prolonged Percutaneous Trasluminal Angioplasty (PTA) balloon inflation. Overall technical success was 39/48 (81%). Kaplan-Meier Primary and secondary patency rates were 72 and 78% at 30, 62 and 73% at 90 and 36 and 67% at 180 days, respectively. Secondary patency rates remained over 50% at 1 year. There were no additional complications caused by these maneuvers. Discussions and conclusion: The majority of complications occurring during percutaneous thrombolysis/thrombectomy of thrombosed access grafts, can be treated at the same sitting allowing completion of the recanalization procedure and usage of the same access for hemodialysis.

  15. Discovery of a cAMP deaminase that quenches cyclic AMP-dependent regulation. (United States)

    Goble, Alissa M; Feng, Youjun; Raushel, Frank M; Cronan, John E


    An enzyme of unknown function within the amidohydrolase superfamily was discovered to catalyze the hydrolysis of the universal second messenger, cyclic-3',5'-adenosine monophosphate (cAMP). The enzyme, which we have named CadD, is encoded by the human pathogenic bacterium Leptospira interrogans. Although CadD is annotated as an adenosine deaminase, the protein specifically deaminates cAMP to cyclic-3',5'-inosine monophosphate (cIMP) with a kcat/Km of 2.7 ± 0.4 × 10(5) M(-1) s(-1) and has no activity on adenosine, adenine, or 5'-adenosine monophosphate (AMP). This is the first identification of a deaminase specific for cAMP. Expression of CadD in Escherichia coli mimics the loss of adenylate cyclase in that it blocks growth on carbon sources that require the cAMP-CRP transcriptional activator complex for expression of the cognate genes. The cIMP reaction product cannot replace cAMP as the ligand for CRP binding to DNA in vitro and cIMP is a very poor competitor of cAMP activation of CRP for DNA binding. Transcriptional analyses indicate that CadD expression represses expression of several cAMP-CRP dependent genes. CadD adds a new activity to the cAMP metabolic network and may be a useful tool in intracellular study of cAMP-dependent processes.

  16. Cyclic AMP (cAMP)-mediated stimulation of adipocyte differentiation requires the synergistic action of Epac- and cAMP-dependent protein kinase-dependent processes

    DEFF Research Database (Denmark)

    Petersen, Rasmus Koefoed; Madsen, Lise; Pedersen, Lone Møller;


    Cyclic AMP (cAMP)-dependent processes are pivotal during the early stages of adipocyte differentiation. We show that exchange protein directly activated by cAMP (Epac), which functions as a guanine nucleotide exchange factor for the Ras-like GTPases Rap1 and Rap2, was required for cAMP-dependent ......Cyclic AMP (cAMP)-dependent processes are pivotal during the early stages of adipocyte differentiation. We show that exchange protein directly activated by cAMP (Epac), which functions as a guanine nucleotide exchange factor for the Ras-like GTPases Rap1 and Rap2, was required for c......AMP-dependent stimulation of adipocyte differentiation. Epac, working via Rap, acted synergistically with cAMP-dependent protein kinase (protein kinase A [PKA]) to promote adipogenesis. The major role of PKA was to down-regulate Rho and Rho-kinase activity, rather than to enhance CREB phosphorylation. Suppression of Rho...

  17. Warmer amps for the LHC

    CERN Multimedia

    Anaïs Schaeffer


    CERN is working together with an Italian company to develop superconducting cables that can function at temperatures of up to 25 K (-248°C). This will make it possible to move LHC magnet power supplies out of the tunnel, protecting them from exposure to the showers of very high-energy particles produced by the accelerator.   Figure 1: devices of this type, which measure approximately 10 metres in length, are inserted between the accelerating magnets at different points along the LHC. When it comes to consuming electricity, the magnets that steer particles through large accelerators can be characterised with just one word: greedy. For the LHC, the total current can reach 1.5 million amps. At the present time, this current is brought in via copper cables of up to 10 cm in diameter. In the tunnel, these cables connect the current leads - which provide the transition between the ambient-temperature cables and the magnets in their bath of superfluid helium - to the power supply. In the a...

  18. 21 CFR 862.1230 - Cyclic AMP test system. (United States)


    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cyclic AMP test system. 862.1230 Section 862.1230....1230 Cyclic AMP test system. (a) Identification. A cyclic AMP test system is a device intended to measure the level of adenosine 3′, 5′-monophosphate (cyclic AMP) in plasma, urine, and other body...

  19. Prolongation structures for supersymmetric equations

    NARCIS (Netherlands)

    Roelofs, G.H.M.; Hijligenberg, van den N.W.


    The well known prolongation technique of Wahlquist and Estabrook (1975) for nonlinear evolution equations is generalized for supersymmetric equations and applied to the supersymmetric extension of the KdV equation of Manin-Radul. Using the theory of Kac-Moody Lie superalgebras, the explicit form of

  20. Prolonged unexplained fatigue in paediatrics

    NARCIS (Netherlands)

    Bakker, R.J.


    Prolonged Unexplained Fatigue in Paediatrics. Fatigue, as the result of mental or physical exertion, will disappear after rest, drinks and food. Fatigue as a symptom of illness will recover with the recovering of the illness. But when fatigue is ongoing for a long time, and not the result of exertio

  1. Pediatric burn wound impetigo after grafting. (United States)

    Aikins, Kimberly; Prasad, Narayan; Menon, Seema; Harvey, John G; Holland, Andrew J A


    Modern burn care techniques have reduced the risk of infection of the acute burn wound, resulting in more rapid healing and a lower incidence of graft loss. Secondary breakdown may still occur. The loss of epithelium in association with multifocal superficial abscesses and ulceration has been termed burns impetigo. This may result in considerable morbidity and require prolonged treatment. The events preceding development, the impact on the patient, and the ideal treatment appear unclear and poorly reported. In 5 years, between 2006 and 2011, 406 pediatric burns were treated with skin grafts, with 7% developing burns impetigo. Time to resolution ranged from 5 to 241 days: the mean time to complete healing was greatest with conservative management (96 days), followed by antibacterial dressings (37 days), oral antibiotics (36 days), topical steroids (16 days), and oral antibiotics in combination with topical steroids (13.5 days). Burns impetigo resulted in significant morbidity, requiring multiple visits to the treatment center and prolonged symptoms. Delay in diagnosis and treatment resulted in worse outcomes. Prompt consideration of burns impetigo should occur when postgraft patients present with suggestive clinical signs and treatment with oral antibiotics plus topical steroids should be considered.

  2. Meta-Symplectic Geometry of 3rd Order Monge-Ampère Equations and their Characteristics (United States)

    Manno, Gianni; Moreno, Giovanni


    This paper is a natural companion of [Alekseevsky D.V., Alonso Blanco R., Manno G., Pugliese F., Ann. Inst. Fourier (Grenoble) 62 (2012), 497-524, arXiv:1003.5177], generalising its perspectives and results to the context of third-order (2D) Monge-Ampère equations, by using the so-called ''meta-symplectic structure'' associated with the 8D prolongation M^{(1)} of a 5D contact manifold M. We write down a geometric definition of a third-order Monge-Ampère equation in terms of a (class of) differential two-form on M^{(1)}. In particular, the equations corresponding to decomposable forms admit a simple description in terms of certain three-dimensional distributions, which are made from the characteristics of the original equations. We conclude the paper with a study of the intermediate integrals of these special Monge-Ampère equations, herewith called of Goursat type.

  3. Prolonged fever after Infliximab infusion

    Institute of Scientific and Technical Information of China (English)

    Jennifer; Katz; Michael; Frank


    Pharmacologic management for ulcerative colitis (UC) has recently been expanded to include antitumor necrosis factor (TNF) therapy for severe disease. Infliximab, a chimeric monoclonal antibody directed again TNF α was first tested in patients with Crohn’s disease. In addition to serious infections, malignancy, drug induced lupus and other autoimmune diseases, serum sickness-like reactions, neurological disease, and infusion reactions further complicate the use of Infliximab. We report a case of prolonged fever after Infliximab infusion to treat steroid refractory UC.

  4. Post-transplant donor-specific antibody production and graft outcome in kidney transplantation: results of sixteen-year monitoring by flow cytometry. (United States)

    Piazza, Antonina; Poggi, Elvira; Ozzella, Giuseppina; Borrelli, Laura; Scornajenghi, Alessandra; Iaria, Giuseppe; Tisone, Giuseppe; Adorno, Domenico


    Our data show that monitoring by sensitive flow cytometric techniques of the de novo production of anti-HLA antibodies in patients receiving kidney transplantation is a useful and noninvasive tool to identify the onset of an immune response towards the graft before any clinical manifestation of antibody-mediated graft injury. Consequently prospective posttransplant monitoring of anti-HLA donor-directed antibodies may offer the chance to realize an effective clinical intervention in order to prevent graft dysfunction and to prolong graft survival. The long follow-up period of the study allowed us to demonstrate a very low graft survival rate in patients who developed donor-specific HLA antibodies in comparison with patients who did not have antibodies, thus confirming the "humoral theory of transplantation". The posttransplant production of anti-HLA antibodies can predict not only graft failure but also chronic dysfunction of the graft. Moreover, our findings suggest that graft survival is influenced by the epitope- and locus-specificity of anti-HLA donor-directed antibodies. The interval between antibody appearance and loss of graft function was short in some patients but reached several years in others. Moreover, some patients showed consistent production of antibodies for many years and an uneventful clinical status. These findings suggest a mechanism of graft "accommodation" or the production of "harmless" antibodies. Immunosuppressive drug combinations able to inhibit T and B cell activation are useful tools to prevent the humoral immune response against graft and consequently to prolong graft survival.

  5. Persistent sodium current is a target for cAMP-induced neuronal plasticity in a state-setting modulatory interneuron. (United States)

    Nikitin, E S; Kiss, T; Staras, K; O'shea, M; Benjamin, P R; Kemenes, G


    We have identified a TTX-resistant low-threshold persistent inward sodium current in the cerebral giant cells (CGCs) of Lymnaea, an important state-setting modulatory cell type of molluscan feeding networks. This current has slow voltage-dependent activation and de-activation kinetics, ultra-slow inactivation kinetics and fast de-inactivation kinetics. It activates at approximately -90 mV, peaks at approximately -30 mV, reverses at approximately +35 mV and does not show full voltage-dependent inactivation even at positive voltage steps. Lithium-sodium replacement experiments indicate that the persistent sodium current makes a significant contribution to the CGC membrane potential. Injection of cyclic adenosine monophosphate (cAMP) into the CGC cell body produces a large increase in the persistent sodium current that lasts for several hours. cAMP injection also leads to increased bursting, a significant decrease in the resistance and a significant depolarization of the soma membrane, indicating that cAMP-dependent mechanisms induce prolonged neuronal plasticity in the CGCs. Our observations provide the first link between cAMP-mediated modulation of a TTX-resistant persistent sodium current and prolonged neuronal plasticity in an identified modulatory cell type that plays an important role in behavioral state setting.

  6. Purification, characterization, and sequencing of antimicrobial peptides, Cy-AMP1, Cy-AMP2, and Cy-AMP3, from the Cycad (Cycas revoluta) seeds. (United States)

    Yokoyama, Seiya; Kato, Kouji; Koba, Atsuko; Minami, Yuji; Watanabe, Keiichi; Yagi, Fumio


    Novel antimicrobial peptides (AMP), designated Cy-AMP1, Cy-AMP2, and Cy-AMP3, were purified from seeds of the cycad (Cycas revoluta) by a CM cellulofine column, ion-exchange HPLC on SP COSMOGEL, and reverse-phase HPLC. They had molecular masses of 4583.2 Da, 4568.9 Da and 9275.8 Da, respectively, by MALDI-TOF MS analysis. Half of the amino acid residues of Cy-AMP1 and Cy-AMP2 were cysteine, glycine and proline, and their sequences were similar. The sequence of Cy-AMP3 showed high homology to various lipid transfer proteins. For Cy-AMP1 and Cy-AMP2, the concentrations of peptides required for 50% inhibition (IC(50)) of the growth of plant pathogenic fungi, Gram-positive and Gram-negative bacteria were 7.0-8.9 microg/ml. The Cy-AMP3 had weak antimicrobial activity. The structural and antimicrobial characteristics of Cy-AMP1 and Cy-AMP2 indicated that they are a novel type of antimicrobial peptide belonging to a plant defensin family.

  7. Antifungal effect of antimicrobial peptides (AMPs LR14) derived from Lactobacillus plantarum strain LR/14 and their applications in prevention of grain spoilage. (United States)

    Gupta, Ruchi; Srivastava, Sheela


    The concern for food safety has led to an increased interest in the development of novel antimicrobials. Keeping this aim in mind, we have investigated the antifungal effect of antimicrobial peptides (AMPs LR14) produced by Lactobacillus plantarum strain LR/14 against four spoilage fungi, namely, Aspergillus niger, Rhizopus stolonifer, Mucor racemosus and Penicillium chrysogenum. Interestingly, all the four fungi were inhibited, suggesting that AMPs LR14 exhibited anti-fungal property. The peptides inhibited both, the spore germination and hyphal growth, however, the former stage was found to be more susceptible. The hyphal extensions were also inhibited in a dose-dependent manner. Viability test of treated spores confirmed the fungicidal activity of AMPs LR14. AMPs LR14 were also studied for the prevention of wheat grain spoilage under storage. Unhygienic conditions in damp godowns and store-houses, lead to loss of food grains and make them unfit for human consumption due to microbial deterioration. The treatment of wheat seeds with AMPs LR14 prevented fungal growth even after a prolonged storage under laboratory conditions for ∼2.5 years. The carbohydrate and protein content of the AMPs LR14-treated seeds denoted no significant loss, but the seed viability was affected as germination was retarded. Such studies have not been reported for any bacteriocin/AMP to the best of our knowledge.

  8. [Chickenpox, burns and grafts]. (United States)

    Rojas Zegers, J; Fidel Avendaño, L


    An outbreak of chickenpox that occurred at the Burns Repair Surgery Unit, Department of Children's Surgery, Hospital R. del Río, between June and November, 1975, is reported. 27 cases of burned children were studied, including analysis of correlations of the stages and outcome of the disease (varicela), the trauma (burns) and the graft (repair surgery). As a result, the authors emphasize the following findings: 1. Burns and their repair are not aggravating factors for varicella. In a small number of cases the exanthema looked more confluent in the graft surgical areas and in the first degree burns healing spontaneously. 2. Usually there was an uneventful outcome of graft repair surgery on a varicella patient, either during the incubation period, the acme or the convalescence. 3. The fact that the outmost intensity of secondary viremia of varicella occurs before the onset of exanthemia, that is, during the late incubation period, is confirmed.

  9. Alveolar bone grafting

    Directory of Open Access Journals (Sweden)

    Lilja Jan


    Full Text Available In patients with cleft lip and palate, bone grafting in the mixed dentition in the residual alveolar cleft has become a well-established procedure. The main advantages can be summarised as follows: stabilisation of the maxillary arch; facilitation of eruption of the canine and sometimes facilitation of the lateral incisor eruption; providing bony support to the teeth adjacent to the cleft; raising the alar base of the nose; facilitation of closure of an oro-nasal fistula; making it possible to insert a titanium fixture in the grafted site and to obtain favourable periodontal conditions of the teeth within and adjacent to the cleft. The timing of the ABG surgery take into consideration not only eruption of the canine but also that of the lateral incisor, if present. The best time for bone grafting surgery is when a thin shell of bone still covers the soon erupting lateral incisor or canine tooth close to the cleft.

  10. Arteriovenous shunt graft ulceration with sinus and graft epithelialization

    Directory of Open Access Journals (Sweden)

    Pooja Singhal


    Full Text Available Arteriovenous fistula and grafts are used as access sites for patients with chronic kidney disease and are prone for complications. Stent grafts are used to treat access site complications. We report a rare and unusual finding of epithelialization of the sinus tract and the lumen of a polytetrafluoroethylene graft, following ulceration of the overlying skin.

  11. Prolongation of islet allograft survival in mice by combined treatment with pravastatin and low-dose cyclosporine. (United States)

    Arita, S; Kasraie, A; Une, S; Ohtsuka, S; Smith, C V; Mullen, Y


    Pravastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, is known to have suppressive effects on immune and inflammatory cells. We have previously shown in mice and dogs that this agent prevents primary nonfunction of islet iso- and autografts by reducing inflammation at the graft site. The present study was designed to further investigate whether pravastatin has a synergistic effect with cyclosporine (Cs) to prolong islet allograft survival in mice. Unpurified 3000 BALB/c newborn islets were transplanted under the renal capsule of a streptozotocin-diabetic C57BL/6 mouse. Pravastatin and Cs were administered for 10 days starting on the day of grafting (day 0). Five groups were set up based on the treatment protocol: group 1, treatment with 40 mg/kg pravastatin; group 2, 30 mg/kg Cs; group 3, 50 mg/kg Cs; group 4, 40 mg/kg pravastatin and 30 mg/kg Cs; group 5, vehicle alone. Graft survival was indicated by blood glucose levels sustained at 250 mg/dl for 2 consecutive days. Hyperglycemia persisted in six of the eight (75%) mice and grafts were rejected in 3.6 +/- 0.5 days (mean +/- SD) in group 5. In group 1, grafts were also rejected in 3.8 +/- 0.8 days, but blood glucose was transiently 60 days, the other rejected the graft on day 15, and the remaining four died with functioning grafts between 9 and 13 days due to Cs toxicity. A combination of a low dose of Cs and pravastatin (group 4) prolonged graft survival for >19 days in five of the eight mice, and for 7-13 days in the remaining three mice. Histological examination of the grafts in this group showed significantly reduced local inflammation. Results indicate a synergistic effect of pravastatin and Cs on prevention of islet allograft rejection.

  12. Preparation and features of polycaprolactone vascular grafts with the incorporated vascular endothelial growth factor

    Energy Technology Data Exchange (ETDEWEB)

    Sevostyanova, V. V., E-mail:; Khodyrevskaya, Y. I.; Glushkova, T. V.; Antonova, L. V.; Kudryavtseva, Y. A.; Barbarash, O. L.; Barbarash, L. S. [Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo (Russian Federation)


    The development of tissue-engineered small-diameter vascular grafts is an urgent issue in cardiovascular surgery. In this study, we assessed how the incorporation of the vascular endothelial growth factor (VEGF) affects morphological and mechanical properties of polycaprolactone (PCL) vascular grafts along with its release kinetics. Vascular grafts were prepared using two-phase electrospinning. In pursuing our aims, we performed scanning electron microscopy, mechanical testing, and enzyme-linked immunosorbent assay. Our results demonstrated the preservation of a highly porous structure and improvement of PCL/VEGF scaffold mechanical properties as compared to PCL grafts. A prolonged VEGF release testifies the use of this construct as a scaffold for tissue-engineered vascular grafts.

  13. Safe time to warm ischemia and posttransplant survival of liver graft from non-heart-beating donors

    Institute of Scientific and Technical Information of China (English)

    Xiao-Shun He; Yi Ma; Lin-Wei Wu; Wei-Qiang Ju; Jin-Lang Wu; Rui-De Hu; Gui-Hua Chen; Jie-Fu Huang


    AIM: To explore the dynamical changes of histology,histochemistry, energy metabolism, liver microcirculation,liver function and posttransplant survival of liver graft in rats under different warm ischemia times (WIT) and predict the maximum limitation of liver graft to warm ischemia.METHODS: According to WIT, the rats were randomized into 7 groups, with WIT of 0, 10, 15, 20, 30, 45, 60 min,respectively. The recovery changes of above-mentioned indices were observed or measured after liver transplantation. The graft survival and postoperative complications in each subgroup were analyzed.RESULTS: Liver graft injury was reversible and gradually resumed normal structure and function after reperfusion when WIT was less than 30 min. In terms of graft survival,there was no significant difference between subgroups within 30 min WIT. When WIT was prolonged to 45 min,the recipients' long-term survival was severely insulted,and both function and histological structure of liver graft developed irreversible damage when WIT was prolonged to 60 min.CONCLUSION: The present study indicates that rat liver graft can be safely subjected to warm ischemia within 30 min.The levels of ATP, energy charge, activities of glycogen,enzyme-histochemistry of liver graft and its recovery potency after reperfusion may serve as the important criteria to evaluate the quality of liver graft.

  14. Kidney clamp, perfuse, re-implant: a useful technique for graft salvage after vascular complications during kidney transplantation. (United States)

    Mekeel, Kristin L; Halldorson, Jeffery B; Berumen, Jennifer A; Hemming, Alan W


    Although intra-operative vascular complications during renal transplantation are rare, injuries associated with prolonged ischemia may lead to graft threatening early and late complications. This series describes a novel technique for intra-operative repair of vascular complications in five patients over a three-yr period. The method consists of rapid graft nephrectomy and re-preservation of the graft with cold University of Wisconsin solution, which allows for controlled/precise back table repair of the vascular injury without incurring prolonged warm ischemia time. In three cases, the donor renal vein (2) and donor renal artery (1) were damaged and required back table reconstruction. In two cases, the recipient iliac artery needed reconstruction. Three of the five cases used deceased donor iliac vessels from another donor for reconstruction. Two patients required postoperative dialysis for delayed graft function for three to nine d (average six d) and two patients had slow graft function. All grafts were functioning at 17 months (mean) after transplant, with a median serum of 1.61 mg/dL (0.74-3.69). This series demonstrates the effectiveness of kidney clamp, perfuse, resuscitate as an effective intra-operative technique to salvage grafts after vascular injury. Although the grafts may suffer from delayed or slow graft function, excellent long-term function is attainable.

  15. Detection of imminent vein graft occlusion: what is the optimal surveillance program? (United States)

    Tinder, Chelsey N; Bandyk, Dennis F


    The prediction of infrainguinal vein bypass failure remains an inexact judgment. Patient demographics, technical factors, and vascular laboratory graft surveillance testing are helpful in identifying a high-risk graft cohort. The optimal surveillance program to detect the bypass at risk for imminent occlusion continues to be developed, but required elements are known and include clinical assessment for new or changes in limb ischemia symptoms, measurement of ankle and/or toe systolic pressure, and duplex ultrasound imaging of the bypass graft. Duplex ultrasound assessment of bypass hemodynamics may be the most accurate method to detect imminent vein graft occlusion. The finding of low graft flow during intraoperative assessment or at a scheduled surveillance study predicts failure; and if associated with an occlusive lesion, a graft revision can prolong patency. The most common abnormality producing graft failure is conduit stenosis caused by myointimal hyperplasia; and the majority can be repaired by an endovascular intervention. Frequency of testing to detect the failing bypass should be individualized to the patient, the type of arterial bypass, and prior duplex ultrasound scan findings. The focus of surveillance is on identification of the low-flow arterial bypass and timely repair of detected critical stenosis defined by duplex velocity spectra criteria of a peak systolic velocity 300 cm/s and peak systolic velocity ratio across the stenosis >3.5-correlating with >70% diameter-reducing stenosis. When conducted appropriately, a graft surveillance program should result in an unexpected graft failure rate of <3% per year.

  16. Escherichia coli exports cyclic AMP via TolC. (United States)

    Hantke, Klaus; Winkler, Karin; Schultz, Joachim E


    In Escherichia coli more than 180 genes are regulated by the cyclic AMP (cAMP)-cAMP receptor protein (CRP) complex. However, more than 90% of cAMP that is made by intracellular adenylyl cyclases is found in the culture medium. How is cAMP exported from E. coli? In a tolC mutant, 0.03 mM IPTG (isopropyl-β-d-thiogalactopyranoside) was sufficient to induce β-galactosidase compared to 0.1 mM IPTG in the parent strain. In a cya mutant unable to produce cAMP about 1 mM extracellular cAMP was required to induce β-galactosidase, whereas in a cya tolC mutant 0.1 mM cAMP was sufficient. When cAMP in E. coli cya was generated intracellularly by a recombinant, weakly active adenylyl cyclase from Corynebacterium glutamicum, the critical level of cAMP necessary for induction of maltose degradation was only achieved in a tolC mutant and not in the parent strain. Deletion of a putative cAMP phosphodiesterase of E. coli, CpdA, resulted in a slightly similar, yet more diffuse phenotype. The data demonstrate that export of cAMP via TolC is a most efficient way of E. coli to lower high concentrations of cAMP in the cell and maintain its sensitivity in changing metabolic environments.

  17. Effect of different carboxylic acids in cyclodextrin functionalization of cellulose nanocrystals for prolonged release of carvacrol. (United States)

    Castro, D O; Tabary, N; Martel, B; Gandini, A; Belgacem, N; Bras, J


    Current investigations deal with new surface functionalization strategy of nanocrystalline cellulose-based substrates to impart active molecule release properties. In this study, cellulose nanocrystals (CNC) were surface-functionalized with β-cyclodextrin (β-CD) using succinic acid (SA) and fumaric acid (FA) as bridging agents. The main objective of this surface modification performed only in aqueous media was to obtain new active materials able to release antibacterial molecules over a prolonged period of time. The reactions were conducted by immersing the CNC film into a solution composed of β-CD, SA and FA, leading to CNC grafting. The materials were characterized by infrared spectroscopy (FT-IR), Quartz crystal microbalance-dissipation (QCM-D), AFM and phenolphthalein (PhP) was used to determine the efficiency of CNC grafting with β-CD. The results indicated that β-CD was successfully attached to the CNC backbone through the formation of ester bonds. Furthermore, carvacrol was entrapped by the attached β-CD and a prolonged release was confirmed. In particular, CNC grafted to β-CD in the presence of FA was selected as the best solution. The antibacterial activity and the controlled release were studied for this sample. Considerably longer bacterial activity against B. subtilis was observed for CNC grafted to β-CD compared to CNC and CNC-FA, confirming the promising impact of the present strategy.

  18. Primary renal graft thrombosis

    NARCIS (Netherlands)

    Bakir, N; Sluiter, WJ; Ploeg, RJ; van Son, WJ; Tegzess, Adam


    Background. Renal allograft thrombosis is a serious complication of kidney transplantation that ultimately leads to graft loss. Its association with acute and hyperacute rejection is well documented; however, in a large proportion of patients the precise cause remains obscure. The exact incidence an

  19. Study on biotribological properties of UHMWPE grafted with MPDSAH. (United States)

    Deng, Yaling; Xiong, Dangsheng; Shao, Silong


    In order to prolong the service life of artificial joints, a zwitterion monomer of MPDSAH ((3-(methacryloylamino)propyl)dimethyl (3-sulfopropyl)ammonium hydroxide) was grafted onto ultra-high molecular weight polyethylene (UHMWPE) powders to construct a brush-like structure by UV irradiation, and then the grafted UHMWPE powders were hot pressed as the bulk materials. The wettability of bulk materials surface with different monomer concentrations was analyzed. The tribological properties of modified UHMWPE bulk materials were investigated under distilled water and saline by sliding against stainless steel ball. The measurement of Fourier-transform infrared (FT-IR) spectroscopy indicates that MPDSAH is successfully grafted onto the surface of UHMWPE powders by UV irradiation. The contact angles of modified UHMWPE are decreased and the surface wettability is effectively improved. The friction coefficient of the modified sample is lower than that of untreated UHMWPE in aqueous lubricants during a long-term friction. With the increase of monomer concentration, the wear rate of grafted UHMWPE decreases gradually in distilled water. The grafting hydrophilic macromolecule polymer is helpful to form a lubricating film of water, which leads to the improvement of the lubricity of UHMWPE.

  20. AMP is an adenosine A1 receptor agonist. (United States)

    Rittiner, Joseph E; Korboukh, Ilia; Hull-Ryde, Emily A; Jin, Jian; Janzen, William P; Frye, Stephen V; Zylka, Mark J


    Numerous receptors for ATP, ADP, and adenosine exist; however, it is currently unknown whether a receptor for the related nucleotide adenosine 5'-monophosphate (AMP) exists. Using a novel cell-based assay to visualize adenosine receptor activation in real time, we found that AMP and a non-hydrolyzable AMP analog (deoxyadenosine 5'-monophosphonate, ACP) directly activated the adenosine A(1) receptor (A(1)R). In contrast, AMP only activated the adenosine A(2B) receptor (A(2B)R) after hydrolysis to adenosine by ecto-5'-nucleotidase (NT5E, CD73) or prostatic acid phosphatase (PAP, ACPP). Adenosine and AMP were equipotent human A(1)R agonists in our real-time assay and in a cAMP accumulation assay. ACP also depressed cAMP levels in mouse cortical neurons through activation of endogenous A(1)R. Non-selective purinergic receptor antagonists (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid and suramin) did not block adenosine- or AMP-evoked activation. Moreover, mutation of His-251 in the human A(1)R ligand binding pocket reduced AMP potency without affecting adenosine potency. In contrast, mutation of a different binding pocket residue (His-278) eliminated responses to AMP and to adenosine. Taken together, our study indicates that the physiologically relevant nucleotide AMP is a full agonist of A(1)R. In addition, our study suggests that some of the physiological effects of AMP may be direct, and not indirect through ectonucleotidases that hydrolyze this nucleotide to adenosine.

  1. 7 CFR 772.14 - Reamortization of AMP loans. (United States)


    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Reamortization of AMP loans. 772.14 Section 772.14... AGRICULTURE SPECIAL PROGRAMS SERVICING MINOR PROGRAM LOANS § 772.14 Reamortization of AMP loans. The Agency may approve reamortization of AMP loans provided: (a) There is no extension of the final maturity...

  2. S-AMP: Approximate Message Passing for General Matrix Ensembles

    DEFF Research Database (Denmark)

    Cakmak, Burak; Winther, Ole; Fleury, Bernard H.


    We propose a novel iterative estimation algorithm for linear observation models called S-AMP. The fixed points of S-AMP are the stationary points of the exact Gibbs free energy under a set of (first- and second-) moment consistency constraints in the large system limit. S-AMP extends...

  3. Multiple facets of cAMP signalling and physiological impact : cAMP compartmentalization in the lung

    NARCIS (Netherlands)

    Oldenburger, Anouk; Maarsingh, Harm; Schmidt, Martina


    Therapies involving elevation of the endogenous suppressor cyclic AMP (cAMP) are currently used in the treatment of several chronic inflammatory disorders, including chronic obstructive pulmonary disease (COPD). Characteristics of COPD are airway obstruction, airway inflammation and airway remodelli

  4. Detection of cyclic di-AMP using a competitive ELISA with a unique pneumococcal cyclic di-AMP binding protein (United States)

    Underwood, Adam J.; Zhang, Yang; Metzger, Dennis W.; Bai, Guangchun


    Cyclic di-AMP (c-di-AMP) is a signaling molecule that has been shown to play important roles in bacterial physiology and infections. Currently, c-di-AMP detection and quantification relies mostly on the use of high-performance liquid chromatography (HPLC) or liquid chromatography-mass spectrometry (LC-MS). In this study, a competitive enzyme-linked immunosorbent assay (ELISA) for the quantification of c-di-AMP was developed, which utilizes a novel pneumococcal c-di-AMP binding protein (CabP) and a newly commercialized c-di-AMP derivative. With this new method, c-di-AMP concentrations in biological samples can be quickly and accurately quantified. Furthermore, this assay is much more efficient than current methods as it requires less overall cost and training while processing many samples at once. Therefore, this assay can be extensively used in research into c-di-AMP signaling. PMID:25239824

  5. Prolonged calcitonin receptor signaling by salmon, but not human calcitonin, reveals ligand bias.

    Directory of Open Access Journals (Sweden)

    Kim Vietz Andreassen

    Full Text Available Salmon calcitonin (sCT and human calcitonin (hCT are pharmacologically distinct. However, the reason for the differences is unclear. Here we analyze the differences between sCT and hCT on the human calcitonin receptor (CT(aR with respect to activation of cAMP signaling, β-arrestin recruitment, ligand binding kinetics and internalization. The study was conducted using mammalian cell lines heterologously expressing the human CT(a receptor. CT(aR downstream signaling was investigated with dose response profiles for cAMP production and β-arrestin recruitment for sCT and hCT during short term (<2 hours and prolonged (up to 72 hours stimulation. CT(aR kinetics and internalization was investigated with radio-labeled sCT and hCT ligands on cultured cells and isolated membrane preparations from the same cell line. We found that sCT and hCT are equipotent during short-term stimulations with differences manifesting themselves only during long-term stimulation with sCT inducing a prolonged activation up to 72 hours, while hCT loses activity markedly earlier. The prolonged sCT stimulation of both cAMP accumulation and β-arrestin recruitment was attenuated, but not abrogated by acid wash, suggesting a role for sCT activated internalized receptors. We have demonstrated a novel phenomenon, namely that two distinct CT(aR downstream signaling activation patterns are activated by two related ligands, thereby highlighting qualitatively different signaling responses in vitro that could have implications for sCT use in vivo.

  6. Prolonged calcitonin receptor signaling by salmon, but not human calcitonin, reveals ligand bias. (United States)

    Andreassen, Kim Vietz; Hjuler, Sara Toftegaard; Furness, Sebastian G; Sexton, Patrick M; Christopoulos, Arthur; Nosjean, Olivier; Karsdal, Morten Asser; Henriksen, Kim


    Salmon calcitonin (sCT) and human calcitonin (hCT) are pharmacologically distinct. However, the reason for the differences is unclear. Here we analyze the differences between sCT and hCT on the human calcitonin receptor (CT(a)R) with respect to activation of cAMP signaling, β-arrestin recruitment, ligand binding kinetics and internalization. The study was conducted using mammalian cell lines heterologously expressing the human CT(a) receptor. CT(a)R downstream signaling was investigated with dose response profiles for cAMP production and β-arrestin recruitment for sCT and hCT during short term (<2 hours) and prolonged (up to 72 hours) stimulation. CT(a)R kinetics and internalization was investigated with radio-labeled sCT and hCT ligands on cultured cells and isolated membrane preparations from the same cell line. We found that sCT and hCT are equipotent during short-term stimulations with differences manifesting themselves only during long-term stimulation with sCT inducing a prolonged activation up to 72 hours, while hCT loses activity markedly earlier. The prolonged sCT stimulation of both cAMP accumulation and β-arrestin recruitment was attenuated, but not abrogated by acid wash, suggesting a role for sCT activated internalized receptors. We have demonstrated a novel phenomenon, namely that two distinct CT(a)R downstream signaling activation patterns are activated by two related ligands, thereby highlighting qualitatively different signaling responses in vitro that could have implications for sCT use in vivo.

  7. Synthesis and super-swelling behavior of a novel low salt-sensitive protein-based superabsorbent hydrogel: collagen-g-poly(AMPS)



    Superabsorbent polymers are obtained by the graft copolymerization of 2-acrylamido-2-methylpropanesul- fonic acid (AMPS) monomer onto collagen, using ammonium persulfate as a free radical initiator in the presence of methylene bisacrylamide as a crosslinker. Infrared spectroscopy and TGA thermal analysis were carried out to confirm the chemical structure of the hydrogel. Moreover, morphology of the samples was examined by scanning electron microscopy (SEM). The effect of reaction var...

  8. A Method for Studying cAMP-relay in Dictyostelium discoideum : the Effect of Temperature on cAMP-relay

    NARCIS (Netherlands)

    Haastert, Peter J.M. van


    A simple assay has been developed to quantify the cAMP-relay in Dictyostelium discoideum. The assay is based on the stimulation of cells, in the presence of a phosphodiesterase inhibitor, with 2'-deoxyadenosine 3',5'-monophosphate (dcAMP) at a concentration which saturates cell surface cAMP receptor

  9. Clinical consequences of infected arteriovenous grafts in hemodialysis patients. (United States)

    Minga, T E; Flanagan, K H; Allon, M


    .85 episodes of bacteremia while they were catheter dependent. In conclusion, graft infection results in substantial morbidity, prolonged dependence on dialysis catheters, and multiple vascular-access procedures.

  10. [Grafting of carotid arteries]. (United States)

    Belov, Iu V; Stepanenko, A B; Gens, A P; Bazylev, V V; Seleznev, M N; Savichev, D D


    Over 5-years, 167 reconstructive surgeries for stenosis of internal carotid arteries (ICA) were performed in 124 patients. Mean age of the patients was 63.5 years. One hundred and twenty-nine carotid endarterectomies (CEAE) in 86 patients and 38 reconstructive operations of ICA in 38 patients were performed. There were no lethal outcomes in short- and long-term postoperative period. In short-term period after prosthesis of ICA restenosis was revealed in 3% patients, after eversion CEAE in 3% patients the embolism was seen, after standard CEAE restenosis were diagnosed in 8% patients and thrombosis -- in 3%. In long-term period after grafting of ICA the strokes were seen in 3%, stenosis -- in 6% patients, after eversion endarterectomy -- in 0 and 3% patients, and after standard CEAE -- in 3 and 24% patients, respectively. It is concluded that grafting of ICA is adequate surgical method of reconstruction and stroke prevention in specific variants of carotid atherosclerosis.

  11. Negative impact of prolonged cold storage time before machine perfusion preservation in donation after circulatory death kidney transplantation. (United States)

    Paloyo, Siegfredo; Sageshima, Junichiro; Gaynor, Jeffrey J; Chen, Linda; Ciancio, Gaetano; Burke, George W


    Kidney grafts are often preserved initially in static cold storage (CS) and subsequently on hypothermic machine perfusion (MP). However, the impact of CS/MP time on transplant outcome remains unclear. We evaluated the effect of prolonged CS/MP time in a single-center retrospective cohort of 59 donation after circulatory death (DCD) and 177 matched donation after brain death (DBD) kidney-alone transplant recipients. With mean overall CS/MP times of 6.0 h/30.0 h, overall incidence of delayed graft function (DGF) was higher in DCD transplants (30.5%) than DBD transplants (7.3%, P time (P = 0.0002), male recipient (P = 0.02), and longer MP time (P = 0.08) were associated with higher DGF incidence. In evaluating the joint effects of donor type (DBD vs. DCD), CS time (time (time ≥36 h (P = 0.003) across each donor type and CS time stratum, whereas the unfavorable effect of CS time ≥6 h (P = 0.01) is primarily seen among DCD recipients. Prolonged cold ischemia time had no unfavorable effect on renal function or graft survival at 12mo post-transplant. Long CS/MP time detrimentally affects early DCD/DBD kidney transplant outcome when grafts were mainly preserved by MP; prolonged CS time before MP has a particularly negative impact in DCD kidney transplantation.

  12. Dual grafts in adult-to-adult living donor liver transplantation: a single center experience in Taiwan. (United States)

    Yang, Chin-Hsiang; Chen, Chao-Long; Wang, Chih-Chi; Concejero, Allan M; Wang, Shih-Ho; Liu, Yueh-Wei; Yong, Chee-Chien; Lin, Tsan-Shiun


    Volume mismatch is encountered when a single live donor cannot provide adequate graft volume to the recipient with a remnant liver volume which is safe for donation. Our objective is to present our experience in living donor liver transplantation using dual grafts. Record review of 4 dual graft recipients was done. The results were compared with 122 consecutive patients who received a single right lobe. All dual graft recipients were surviving with satisfactory liver function at a median follow-up of 21 months. Two recipients received 1 right and 1 left lobe graft, while the other 2 recipients received 2 left lobe grafts. One donor developed biloma and was managed by percutaneous drainage. The first recipient required re-laparotomy for postoperative bleeding. The second recipient underwent re-laparotomy for bile leak. The third recipient developed grade II decubitus ulcers due to a prolonged sedentary position. When compared with recipients who received a single right lobe, the operative time was prolonged in the dual graft group. There was no apparent increase in the rate of vascular and biliary complications or the incidence of acute cellular rejection. Actuarial patient survivals were comparable in both groups. Dual graft transplantation provides sufficient volume in the recipient without jeopardizing donor safety.

  13. Buccal Mucosal Graft Urethroplasty

    Directory of Open Access Journals (Sweden)

    Angela M. Arlen


    Full Text Available At our institution, the majority of buccal mucosal graft urethroplasties are performed using a two-team approach with an otolaryngologic surgeon. We report our two-surgeon experience with buccal mucosal grafting for reconstruction of all anterior urethral strictures. Twenty-four men underwent autologous buccal mucosal graft urethroplasty between October 2001 and September 2008 for recurrent urethral stricture disease. Twenty-two underwent a single-stage repair and two underwent a two-stage repair. Medical charts were retrospectively reviewed for demographics, comorbidities, etiology, location and length of stricture, and prior interventions in order to identify predictors of buccal urethroplasty success, defined as no evidence of stricture recurrence. All patients underwent retrograde urethrogram and cystoscopy. Operative and anesthesia times were evaluated. We determined an overall success rate of 83.3% (20 of 24 cases. Mean anesthesia time for single-stage urethroplasty was 155 min and mean operative time was 123 min. One of the two two-stage urethroplasties experienced stricture recurrence (50%. The single-stage buccal graft success rate was 86.4% (19 of 22 cases. Two of the four who developed recurrent stricture disease that required intervention had undergone a previous mesh urethroplasty. Complications developed in four of 24 patients (16.6%, including superficial wound infection (one, superficial wound dehiscence (two, and abscess/fistula formation requiring reoperation (one. The buccal mucosa is an ideal tissue for both single- and two-stage substitution urethroplasty for patients with recurrent stricture disease. Our two-surgeon technique minimizes anesthesia and operative times, and contributes to the overall high success rate and relatively low complication rate.

  14. Cyclic AMP efflux inhibitors as potential therapeutic agents for leukemia (United States)

    Perez, Dominique R.; Smagley, Yelena; Garcia, Matthew; Carter, Mark B.; Evangelisti, Annette; Matlawska-Wasowska, Ksenia; Winter, Stuart S.; Sklar, Larry A.; Chigaev, Alexandre


    Apoptotic evasion is a hallmark of cancer. We propose that some cancers may evade cell death by regulating 3′-5′-cyclic adenosine monophosphate (cAMP), which is associated with pro-apoptotic signaling. We hypothesize that leukemic cells possess mechanisms that efflux cAMP from the cytoplasm, thus protecting them from apoptosis. Accordingly, cAMP efflux inhibition should result in: cAMP accumulation, activation of cAMP-dependent downstream signaling, viability loss, and apoptosis. We developed a novel assay to assess cAMP efflux and performed screens to identify inhibitors. In an acute myeloid leukemia (AML) model, several identified compounds reduced cAMP efflux, appropriately modulated pathways that are responsive to cAMP elevation (cAMP-responsive element-binding protein phosphorylation, and deactivation of Very Late Antigen-4 integrin), and induced mitochondrial depolarization and caspase activation. Blocking adenylyl cyclase activity was sufficient to reduce effects of the most potent compounds. These compounds also decreased cAMP efflux and viability of B-lineage acute lymphoblastic leukemia (B-ALL) cell lines and primary patient samples, but not of normal primary peripheral blood mononuclear cells. Our data suggest that cAMP efflux is a functional feature that could be therapeutically targeted in leukemia. Furthermore, because some of the identified drugs are currently used for treating other illnesses, this work creates an opportunity for repurposing. PMID:27129155

  15. Phosphodiesterase 4 and compartmentalization of cyclic AMP signaling

    Institute of Scientific and Technical Information of China (English)

    WANG ZhengChao; SHI FangXiong


    Cyclic AMP (cAMP), as a second messenger, plays a critical role in cellular signaling transduction. However, it is not clear how this apparently identical cAMP signal induces divergent physiological responses. The potential explanation that cAMP signaling is compartmentalized was proposed by Buxton and Brunton twenty years ago. Compartmentalization of cAMP signaling allows spatially distinct pools of protein kinase A (PKA) to be differently activated. Research on cAMP signaling has regained impetus in many fields of life sciences due to the progress in understanding cAMP signaling complexity and functional diversity. The cAMP/PKA signaling compartments are maintained by A-kinase anchoring proteins (AKAPs) which bind PKA and other signaling proteins, and by PDEs which hydrolyse cAMP and thus terminate PKA activity. PDE4 enzymes belong to PDE superfamily and stand at a crossroad that allows them to integrate various signaling pathways with that of cAMP in spatially distinct compartments. In the current review, the nomenclature, taxonomy and gene expression of PDE4, and the system and region of its effect are described. In addition, the idiographic molecules, mechanisms, and regulation models of PDE4 are summarized. Furthermore, the important roles PDE4 plays in the maturation of rat granulosa cells and cAMP signaling compartmentalization are discussed.

  16. Prolonged QT interval in Rett syndrome



    Rett syndrome is a severe neurodevelopmental disorder of unknown aetiology. A prolonged QT interval has been described previously in patients with Rett syndrome. To investigate QT prolongation and the presence of cardiac tachyarrhythmias in Rett syndrome electrocardiography and 24 hour Holter monitoring were performed prospectively in a cohort of 34 girls with Rett syndrome. The corrected QT value was prolonged in nine patients. Compared with a group of healthy controls of a...

  17. Cyclic AMP (cAMP) confers drug resistance against DNA damaging agents via PKAIA in CML cells. (United States)

    Xiao, Ling-Yi; Kan, Wai-Ming


    Cyclic adenosine monophosphate (cAMP) regulates many vital functions such as metabolism, proliferation, differentiation and death. Depending on cell types and stimulators, cAMP could either promote or attenuate cell death. cAMP signal can be transduced by protein kinase A (PKA) and/or exchange protein directly activated by cAMP (EPAC). In CML cells, cAMP may suppress their proliferation and enhance their differentiation. However, the role of cAMP on DNA damaging agent toxicity and the mechanism involved has not been studied. In this study, we studied the effect of cAMP on the sensitivity of CML cells to DNA damaging agents. We observed that forskolin (FSK) and dibutyryl-cAMP (DBcAMP) decreased cisplatin and etoposide-induced cell death in K562 cells. Moreover, PKA activator prevented K562 cells from DNA damaging agent-induced cell death while EPAC activator had no effect. Furthermore, we found that the PKA subtype, PKAIA, was involved in cAMP-attenuated resistance in K562 cells. Taken together, our results suggest that increased cAMP level confers CML cells to acquire a novel mechanism against DNA damaging agent toxicity via PKAIA. Thus, PKAIA inhibitor may be helpful in overcoming the resistance to DNA damaging agents in CML cells.

  18. The Monge-Ampère equation

    CERN Document Server

    Gutiérrez, Cristian E


    Now in its second edition, this monograph explores the Monge-Ampère equation and the latest advances in its study and applications. It provides an essentially self-contained systematic exposition of the theory of weak solutions, including regularity results by L. A. Caffarelli. The geometric aspects of this theory are stressed using techniques from harmonic analysis, such as covering lemmas and set decompositions. An effort is made to present complete proofs of all theorems, and examples and exercises are offered to further illustrate important concepts. Some of the topics considered include generalized solutions, non-divergence equations, cross sections, and convex solutions. New to this edition is a chapter on the linearized Monge-Ampère equation and a chapter on interior Hölder estimates for second derivatives. Bibliographic notes, updated and expanded from the first edition, are included at the end of every chapter for further reading on Monge-Ampère-type equations and their diverse applications in th...

  19. The Applied Mathematics for Power Systems (AMPS)

    Energy Technology Data Exchange (ETDEWEB)

    Chertkov, Michael [Los Alamos National Laboratory


    Increased deployment of new technologies, e.g., renewable generation and electric vehicles, is rapidly transforming electrical power networks by crossing previously distinct spatiotemporal scales and invalidating many traditional approaches for designing, analyzing, and operating power grids. This trend is expected to accelerate over the coming years, bringing the disruptive challenge of complexity, but also opportunities to deliver unprecedented efficiency and reliability. Our Applied Mathematics for Power Systems (AMPS) Center will discover, enable, and solve emerging mathematics challenges arising in power systems and, more generally, in complex engineered networks. We will develop foundational applied mathematics resulting in rigorous algorithms and simulation toolboxes for modern and future engineered networks. The AMPS Center deconstruction/reconstruction approach 'deconstructs' complex networks into sub-problems within non-separable spatiotemporal scales, a missing step in 20th century modeling of engineered networks. These sub-problems are addressed within the appropriate AMPS foundational pillar - complex systems, control theory, and optimization theory - and merged or 'reconstructed' at their boundaries into more general mathematical descriptions of complex engineered networks where important new questions are formulated and attacked. These two steps, iterated multiple times, will bridge the growing chasm between the legacy power grid and its future as a complex engineered network.

  20. Directed evolution of the Escherichia coli cAMP receptor protein at the cAMP pocket. (United States)

    Gunasekara, Sanjiva M; Hicks, Matt N; Park, Jin; Brooks, Cory L; Serate, Jose; Saunders, Cameron V; Grover, Simranjeet K; Goto, Joy J; Lee, Jin-Won; Youn, Hwan


    The Escherichia coli cAMP receptor protein (CRP) requires cAMP binding to undergo a conformational change for DNA binding and transcriptional regulation. Two CRP residues, Thr(127) and Ser(128), are known to play important roles in cAMP binding through hydrogen bonding and in the cAMP-induced conformational change, but the connection between the two is not completely clear. Here, we simultaneously randomized the codons for these two residues and selected CRP mutants displaying high CRP activity in a cAMP-producing E. coli. Many different CRP mutants satisfied the screening condition for high CRP activity, including those that cannot form any hydrogen bonds with the incoming cAMP at the two positions. In vitro DNA-binding analysis confirmed that these selected CRP mutants indeed display high CRP activity in response to cAMP. These results indicate that the hydrogen bonding ability of the Thr(127) and Ser(128) residues is not critical for the cAMP-induced CRP activation. However, the hydrogen bonding ability of Thr(127) and Ser(128) was found to be important in attaining high cAMP affinity. Computational analysis revealed that most natural cAMP-sensing CRP homologs have Thr/Ser, Thr/Thr, or Thr/Asn at positions 127 and 128. All of these pairs are excellent hydrogen bonding partners and they do not elevate CRP activity in the absence of cAMP. Taken together, our analyses suggest that CRP evolved to have hydrogen bonding residues at the cAMP pocket residues 127 and 128 for performing dual functions: preserving high cAMP affinity and keeping CRP inactive in the absence of cAMP.

  1. Noninvasive imaging of islet grafts using positron-emission tomography (United States)

    Lu, Yuxin; Dang, Hoa; Middleton, Blake; Zhang, Zesong; Washburn, Lorraine; Stout, David B.; Campbell-Thompson, Martha; Atkinson, Mark A.; Phelps, Michael; Gambhir, Sanjiv Sam; Tian, Jide; Kaufman, Daniel L.


    Islet transplantation offers a potential therapy to restore glucose homeostasis in type 1 diabetes patients. However, islet transplantation is not routinely successful because most islet recipients gradually lose graft function. Furthermore, serological markers of islet function are insensitive to islet loss until the latter stages of islet graft rejection. A noninvasive method of monitoring islet grafts would aid in the assessment of islet graft survival and the evaluation of interventions designed to prolong graft survival. Here, we show that recombinant adenovirus can engineer isolated islets to express a positron-emission tomography (PET) reporter gene and that these islets can be repeatedly imaged by using microPET after transplantation into mice. The magnitude of signal from engineered islets implanted into the axillary cavity was directly related to the implanted islet mass. PET signals attenuated over the following weeks because of the transient nature of adenovirus-mediated gene expression. Because the liver is the preferred site for islet implantation in humans, we also tested whether islets could be imaged after transfusion into the mouse liver. Control studies revealed that both intrahepatic islet transplantation and hyperglycemia altered the biodistribution kinetics of the PET probe systemically. Although transplanted islets were dispersed throughout the liver, clear signals from the liver region of mice receiving PET reporter-expressing islets were detectable for several weeks. Viral transduction, PET reporter expression, and repeated microPET imaging had no apparent deleterious effects on islet function after implantation. These studies lay a foundation for noninvasive quantitative assessments of islet graft survival using PET. diabetes | transplantation

  2. Prenatal risk indicators of a prolonged pregnancy

    DEFF Research Database (Denmark)

    Olesen, Annette Wind; Westergaard, Jes Grabow; Olsen, Jørn


    BACKGROUND: Few prenatal risk factors of prolonged pregnancy, a pregnancy of 42 weeks or more, are known. The objective was to examine whether sociodemographic, reproductive, toxicologic, or medical health conditions were associated with the risk of prolonged pregnancy. METHODS: Data from the Dan...

  3. Prolonged Pregnancy: Methods, Causal Determinants and Outcome

    DEFF Research Database (Denmark)

    Olesen, Annette Wind

    Summary Prolonged pregnancy, defined as a pregnancy with a gestational length of 294 days or more, is a frequent condition. It is associated with an increased risk of fetal and maternal complications. Little is known about the aetiology of prolonged pregnancy. The aims of the thesis were 1...

  4. Suction blister grafting - Modifications for easy harvesting and grafting

    Directory of Open Access Journals (Sweden)


    Full Text Available Suction blister grafting is a simple modality of treatment of patients with resistant and stable vitiligo. But raising the blisters may be time consuming and transferring to the recipient site may be difficult as the graft is ultrathin. By doing some modifications we can make the technique simpler and easier. We can decrease the blister induction time by intradermal injection of saline, exposure to Wood′s lamp, intrablister injection of saline. By these methods we can decrease the blister induction time from 2-3 hrs to 45-90 minutes. After harvesting the graft, it can be transferred to the recipient area by taking the graft on a sterile glass slide, on the gloved finger, rolling the graft over a sterile syringe and then spreading on the recipient area, or taking on the sterile wrapper of paraffin dressing and then placing over the recipient area.

  5. Autologous Dendritic Cells Prolong Allograft Survival Through Tmem176b-Dependent Antigen Cross-Presentation (United States)

    Charnet, P.; Savina, A.; Tilly, G.; Gautreau, L.; Carretero-Iglesia, L.; Beriou, G.; Cebrian, I.; Cens, T.; Hepburn, L.; Chiffoleau, E.; Floto, R. A.; Anegon, I.; Amigorena, S.; Hill, M.; Cuturi, M. C.


    The administration of autologous (recipient-derived) tolerogenic dendritic cells (ATDCs) is under clinical evaluation. However, the molecular mechanisms by which these cells prolong graft survival in a donor-specific manner is unknown. Here, we tested mouse ATDCs for their therapeutic potential in a skin transplantation model. ATDC injection in combination with anti-CD3 treatment induced the accumulation of CD8+CD11c+ T cells and significantly prolonged allograft survival. TMEM176B is an intracellular protein expressed in ATDCs and initially identified in allograft tolerance. We show that Tmem176b−/− ATDCs completely failed to trigger both phenomena but recovered their effect when loaded with donor peptides before injection. These results strongly suggested that ATDCs require TMEM176B to cross-present antigens in a tolerogenic fashion. In agreement with this, Tmem176b−/− ATDCs specifically failed to cross-present male antigens or ovalbumin to CD8+ T cells. Finally, we observed that a Tmem176b-dependent cation current controls phagosomal pH, a critical parameter in cross-presentation. Thus, ATDCs require TMEM176B to cross-present donor antigens to induce donor-specific CD8+CD11c+ T cells with regulatory properties and prolong graft survival. PMID:24731243

  6. Preparation and Characterization of Lignin Graft Copolymer as a Filtrate Loss Control Agent for the Hydrocarbon Drilling Industry

    Directory of Open Access Journals (Sweden)

    Mohamad Nasir Mohamad Ibrahim


    Full Text Available Lignin graft copolymer (LGC was prepared using an addition polymerization technique that involved grafting a 2-acrylamido-2-methylpropane sulfonic acid (AMPS monomer onto soda lignin (SL. The optimal polymerization conditions were found to be as follows: soda lignin, 2.0 g; initiator, 3% (w/w potassium persulphate of SL; mass ratio of AMPS to SL, 1:2; reaction time, 7 h; and reaction temperature, 60 °C. The LGC was characterized using a Fourier transform infrared (FTIR spectroscopy, a thermogravimetric analyzer (TGA, and gel permeation chromatography (GPC. The filtrate loss controlling ability of the LGC was evaluated using the American Petroleum Institute Recommended Practice 13-B 1 standard procedures. The results showed that the LGC has remarkable rheological and filtration controlling properties at both room temperature and high aging temperatures (190 °C.

  7. Graft selection in cerebral revascularization. (United States)

    Baaj, Ali A; Agazzi, Siviero; van Loveren, Harry


    Cerebral revascularization constitutes an important treatment modality in the management of complex aneurysms, carotid occlusion, tumor, and moyamoya disease. Graft selection is a critical step in the planning of revascularization surgery, and depends on an understanding of graft and regional hemodynamics, accessibility, and patency rates. The goal of this review is to highlight some of these properties.

  8. Polyether/Polyester Graft Copolymers (United States)

    Bell, Vernon L., Jr.; Wakelyn, N.; Stoakley, D. M.; Proctor, K. M.


    Higher solvent resistance achieved along with lower melting temperature. New technique provides method of preparing copolymers with polypivalolactone segments grafted onto poly (2,6-dimethyl-phenylene oxide) backbone. Process makes strong materials with improved solvent resistance and crystalline, thermally-reversible crosslinks. Resulting graft copolymers easier to fabricate into useful articles, including thin films, sheets, fibers, foams, laminates, and moldings.

  9. Early primary graft failure after a pediatric heart transplant and successful rescue with plasmapheresis, immunoglobulins, and alemtuzumab

    Directory of Open Access Journals (Sweden)

    Shashi Raj


    Full Text Available Early primary graft failure after pediatric orthotopic heart transplantation (OHT has a high mortality rate and can occur due to several causes including but not limited to prolonged graft ischemia time, suboptimal preimplant myocardial preservation, hyperacute rejection, and maladaptation of the graft to the host's hemodynamic status. Mechanical circulatory support with either extracorporeal membrane oxygenation (ECMO or ventricular assist device has been used for the rescue of primary graft failure in pediatric patients after heart transplant. Cardiac arrest before ECMO initiation in these patients is associated with adverse neurologic outcome although those surviving to hospital discharge generally have excellent long-term outcome. We report a case of early primary graft failure after OHT who required ECMO support and successful rescue with plasmapheresis, immunoglobulins, and alemtuzumab.

  10. Radioprotection of the rat parotid gland by cAMP

    Energy Technology Data Exchange (ETDEWEB)

    Sodicoff, M.; Conger, A.D.


    Most earlier studies showing a radioprotective effect by cAMP show only slight degrees of protection. The present study demonstrates a substantial protective effect (DMF, 1.63) of exogenously administered cAMP on the rat parotid gland and supports the mechanism suggested previously for protection afforded the parotid glands by the ..beta..-adrenergic agonist isoproterenol, which is known to elevate endogenous intracellular cAMP.

  11. Temporary Placement of Stent Grafts in Postsurgical Benign Biliary Strictures: a Single Center Experience

    Energy Technology Data Exchange (ETDEWEB)

    Vellody, Ranjith; Willatt, Jnonathon M.; Arabi, Mohammad; Cwikiel, Wojciech B [Division of Interventional Radiology, University of Michigan, Ann Arbor (United States)


    To evaluate the effect of temporary stent graft placement in the treatment of benign anastomotic biliary strictures. Nine patients, five women and four men, 22-64 years old (mean, 47.5 years), with chronic benign biliary anastomotic strictures, refractory to repeated balloon dilations, were treated by prolonged, temporary placement of stent-grafts. Four patients had strictures following a liver transplantation; three of them in bilio-enteric anastomoses and one in a choledocho-choledochostomy. Four of the other five patients had strictures at bilio-enteric anastomoses, which developed after complications following laparoscopic cholecystectomies and in one after a Whipple procedure for duodenal carcinoma. In eight patients, balloon-expandable stent-grafts were placed and one patient was treated by insertion of a self-expanding stent-graft. In the transplant group, treatment of patients with bilio-enteric anastomoses was unsuccessful (mean stent duration, 30 days). The patient treated for stenosis in the choledocho-choledochostomy responded well to consecutive self-expanding stent-graft placement (total placement duration, 112 days). All patients with bilio-enteric anastomoses in the non-transplant group were treated successfully with stent-grafts (mean placement duration, 37 days). Treatment of benign biliary strictures with temporary placement of stent-grafts has a positive effect, but is less successful in patients with strictures developed following a liver transplant.

  12. Radiation grafting on natural films (United States)

    Lacroix, M.; Khan, R.; Senna, M.; Sharmin, N.; Salmieri, S.; Safrany, A.


    Different methods of polymer grafting using gamma irradiation are reported in the present study for the preparation of newly functionalized biodegradable films, and some important properties related to their mechanical and barrier properties are described. Biodegradable films composed of zein and poly(vinyl alcohol) (PVA) were gamma-irradiated in presence of different ratios of acrylic acid (AAc) monomer for compatibilization purpose. Resulting grafted films (zein/PVA-g-AAc) had their puncture strength (PS=37-40 N mm-1) and puncture deformation (PD=6.5-9.8 mm) improved for 30% and 50% PVA in blend, with 5% AAc under 20 kGy. Methylcellulose (MC)-based films were irradiated in the presence of 2-hydroxyethyl methacrylate (HEMA) or silane, in order to determine the effect of monomer grafting on the mechanical properties of films. It was found that grafted films (MC-g-HEMA and MC-g-silane) using 35% monomer performed higher mechanical properties with PS values of 282-296 N mm-1 and PD of 5.0-5.5 mm under 10 kGy. Compatibilized polycaprolactone (PCL)/chitosan composites were developed via grafting silane in chitosan films. Resulting trilayer grafted composite film (PCL/chitosan-g-silane/PCL) presented superior tensile strength (TS=22 MPa) via possible improvement of interfacial adhesion (PCL/chitosan) when using 25% silane under 10 kGy. Finally, MC-based films containing crystalline nanocellulose (CNC) as a filling agent were prepared and irradiated in presence of trimethylolpropane trimethacrylate (TMPTMA) as a grafted plasticizer. Grafted films (MC-g-TMPTMA) presented superior mechanical properties with a TS of 47.9 MPa and a tensile modulus (TM) of 1792 MPa, possibly due to high yield formation of radicals to promote TMPTMA grafting during irradiation. The addition of CNC led to an additional improvement of the barrier properties, with a significant 25% reduction of water vapor permeability (WVP) of grafted films.

  13. Amp C酶及其耐药性

    Institute of Scientific and Technical Information of China (English)

    赵虎; 孔宪涛


    本文叙述了Amp C酶的定义、Amp C酶的基因结构与功能、Amp C酶的合成、Amp C酶的耐药性及其耐药机制,以及Amp C酶的检测方法。Amp C酶是由肠杆菌科细菌和铜绿假单胞菌等产生的一类头孢菌素酶,可水解头孢菌素类抗生素,导致细菌对这类抗生素产生耐药性。编码产生Amp C酶的基因包括结构基因-amp C和四种调控基因-ampR、ampD、ampE以及ampG,但其具体的转录、调控机制目前尚未完全明了。Amp C酶的合成具有明显的诱导性,其诱导有菌种依赖性、抗生素依赖性和生长条件依赖性。Amp C酶的耐药机制主要是作用于头胞菌素的β-内酰胺环上的羰基,形成酰化酶中间体,然后在水分子的作用下导致β-内酰胺环开环而失活。大部分Amp C酶都是由细菌染色体所介导,但近年来陆续在质粒上发现这些基因,并在肺炎克雷伯菌、大肠埃希菌、产气肠杆菌和沙门菌中持续高水平的表达,还可以通过质粒在细菌间相互传播,导致耐药菌的广泛传播。产Amp C酶菌株的检测以改良的酶提取物三维试验法较佳。

  14. S-AMP for non-linear observation models

    DEFF Research Database (Denmark)

    Cakmak, Burak; Winther, Ole; Fleury, Bernard H.


    Recently we presented the S-AMP approach, an extension of approximate message passing (AMP), to be able to handle general invariant matrix ensembles. In this contribution we extend S-AMP to non-linear observation models. We obtain generalized AMP (GAMP) as the special case when the measurement...... matrix has zero-mean iid Gaussian entries. Our derivation is based upon 1) deriving expectation-propagation-(EP)-like equations from the stationary-points equations of the Gibbs free energy under first- and second-moment constraints and 2) applying additive free convolution in free probability theory...

  15. AmpC酶的研究进展

    Institute of Scientific and Technical Information of China (English)




  16. Antagonists of chemoattractants reveal separate receptors for cAMP, folic acid and pterin in Dictyostelium

    NARCIS (Netherlands)

    Haastert, Peter J.M. van; Wit, René J.W. de; Konijn, Theo M.


    Adenosine 3’,5’-monophosphate (cAMP), folic acid and pterin are chemoattractants in the cellular slime molds. The cAMP analog, 3’-amino-cAMP, inhibits a chemotactic reaction to cAMP at a concentration at which the analog is chemotactically inactive. The antagonistic effect of 3’-amino-cAMP on the ch

  17. QT Prolongation due to Graves' Disease (United States)

    Deol, Nisha; Tolly, Renee; Manocha, Rohan; Naseer, Maliha


    Hyperthyroidism is a highly prevalent disease affecting over 4 million people in the US. The disease is associated with many cardiac complications including atrial fibrillation and also less commonly with ventricular tachycardia and fibrillation. Many cardiac pathologies have been extensively studied; however, the relationship between hyperthyroidism and rate of ventricular repolarization manifesting as a prolonged QTc interval is not well known. Prolonged QTc interval regardless of thyroid status is a risk factor for cardiovascular mortality and life-threatening ventricular arrhythmia. The mechanism regarding the prolongation of the QT interval in a hyperthyroid patient has not been extensively investigated although its clinical implications are relevant. Herein, we describe a case of prolonged QTc in a patient who presented with signs of hyperthyroidism that was corrected with return to euthyroid status. PMID:28154763

  18. Efficacy of the "baby-sitter" procedure after prolonged denervation. (United States)

    Mersa, B; Tiangco, D A; Terzis, J K


    This study was undertaken to evaluate whether 40 percent of the hypoglossal nerve, which showed optimal efficacy in restoring orbicularis oculi muscle (OOM) function after different percentages of partial neurectomy in a previous study would be effective after prolonged denervation time. Twenty Sprague-Dawley rats were divided into four groups. In first-stage surgery the left facial nerve of all animals was transected at the level of the stylomastoid foramen and main zygomatic branch. Group A (controls) consisted of animals with only left facial nerves transected (no repair). In Groups B, C, and D the facial nerve was transected and the facial musculature was denervated for a period of 4, 8, and 12 weeks respectively. During a second-stage procedure, a 40 percent neurectomy was performed on the hypoglossal nerve. Subsequently, a nerve transfer was performed by coaptations of a saphenous nerve graft to the neurectomized hypoglossal nerve and the main zygomatic branch of the facial nerve that innervated the OOM. Behavioral analysis of blink reflex, electrophysiology, and axon and motor end-plate counts in Groups B, C, and D showed superior results compared to Group A. There was no statistically significant difference observed among Groups B, C, and D (p > 0.05). Despite the diminished number of axons in the zygomatic branch and motor end-plates in the orbicularis oculi muscle after 12 weeks of denervation, there was still sufficient muscle target recovery to effect some eye closure in all groups except the controls. This study demonstrated in this model that the 40 percent partial neurectomy of the XII to VII component of the "baby-sitter" procedure was effective even after prolonged denervation.

  19. Revisiting cAMP signaling in the carotid body

    Directory of Open Access Journals (Sweden)

    Ana Rita eNunes


    Full Text Available Chronic carotid body (CB activation is now recognized as being essential in the development of hypertension and promoting insulin resistance; thus, it is imperative to characterize the chemotransduction mechanisms of this organ in order to modulate its activity and improve patient outcomes. For several years, and although controversial, cyclic adenosine monophosphate (cAMP was considered an important player in initiating the activation of the CB. However, its relevance was partially displaced in the 90s by the emerging role of the mitochondria and molecules such as AMP-activated protein kinase (AMPK and O2-sensitive K+ channels. Neurotransmitters/neuromodulators binding to metabotropic receptors are essential to chemotransmission in the CB, and cAMP is central to this process. cAMP also contributes to raise intracellular Ca2+ levels, and is intimately related to the cellular energetic status (AMP/ATP ratio. Furthermore, cAMP signaling is a target of multiple current pharmacological agents used in clinical practice. This review provides an outline on 1 the classical view of the cAMP-signaling pathway in the CB that originally supported its role in the O2/CO2 sensing mechanism, 2 present recent evidence on CB cAMP neuromodulation and 3 discuss how CB activity is affected by current clinical therapies that modify cAMP-signaling, namely dopaminergic drugs, caffeine (modulation of A2A/A2B receptors and roflumilast (PDE4 inhibitors. cAMP is key to any process that involves metabotropic receptors and the intracellular pathways involved in CB disease states are likely to involve this classical second messenger. Research examining the potential modification of cAMP levels and/or interactions with molecules associated with CB hyperactivity is currently in its beginning and this review will open doors for future explorations.

  20. Graft stability after endothelial keratoplasty

    Directory of Open Access Journals (Sweden)

    Jovanović Vesna


    Full Text Available Bacground/Aim. Techniques for replacing the corneal endothelium have been improved. The host-graft interface is the key to graft adhesion and visual recovery. The aim of this study was to establish graft stability after Descemet stripping with endothelial keratoplasty (DSEK, compare it to the graft stability after endothelial keratoplasty with the intact posterior corneal layers (nDSEK in the rabbit cornea, and to investigate the nature of wound healing. Methods. Adult white rabbits (n = 20 were divided in two experimental groups: ten rabbits underwent monocular DSEK, and ten rabbits underwent endothelial keratoplasty without Descemet stripping (nDSEK. On the second postoperative day a horizontal dislocation of the graft was tried using the Lindstrom roller in each animal. Corneas were processed for the light microscopy study. Results. Rolling the Lindstrom instrument over the corneal surface did not cause horizontal dislocation in any of the operated eyes. In the DSEK group light microscopy revealed the lack of inflammation and fibrosis at the clearly distinctive donor-recipient interface (DRI. Retrocorneal membrane was found in two eyes. In nDSEK group, the host Descemet` s membrane (DM was intact without endothelial cells, with good graft apposition, without inflammation, fibrosis, or retrocorneal membrane. Conclusion. This study suggests that there is no difference in graft stability in DSEK compared to nDSEK in rabbit corneas. Wounds healed at DRI by hypocellular scarring only in both experimental groups.

  1. Unexplained Graft Dysfunction after Heart Transplantation—Role of Novel Molecular Expression Test Score and QTc-Interval: A Case Report

    Directory of Open Access Journals (Sweden)

    Khurram Shahzad


    Full Text Available In the current era of immunosuppressive medications there is increased observed incidence of graft dysfunction in the absence of known histological criteria of rejection after heart transplantation. A noninvasive molecular expression diagnostic test was developed and validated to rule out histological acute cellular rejection. In this paper we present for the first time, longitudinal pattern of changes in this novel diagnostic test score along with QTc-interval in a patient who was admitted with unexplained graft dysfunction. Patient presented with graft failure with negative findings on all known criteria of rejection including acute cellular rejection, antibody mediated rejection and cardiac allograft vasculopathy. The molecular expression test score showed gradual increase and QTc-interval showed gradual prolongation with the gradual decline in graft function. This paper exemplifies that in patients presenting with unexplained graft dysfunction, GEP test score and QTc-interval correlate with the changes in the graft function.

  2. Prolonged renal allograft survival by donor interleukin-6 deficiency: association with decreased alloantibodies and increased intragraft T regulatory cells. (United States)

    Wang, Hao; Guan, Qiunong; Lan, Zhu; Li, Shuyuan; Ge, Wei; Chen, Huifang; Nguan, Christopher Y C; Du, Caigan


    Both humoral and cellular immune responses are involved in renal allograft rejection. Interleukin (IL)-6 is a regulatory cytokine for both B and Foxp3 (forkhead box P3)-expressing regulatory T (Treg) cells. This study was designed to investigate the impact of donor IL-6 production on renal allograft survival. Donor kidneys from IL-6 knockout (KO) vs. wild-type (WT) C57BL/6 mice (H-2(b)) were orthotopically transplanted to nephrotomized BALB/c mice (H-2(d)). Alloantibodies and Treg cells were examined by fluorescence-activated cell sorting analysis. Graft survival was determined by the time to graft failure. Here, we showed that a deficiency in IL-6 expression in donor kidneys significantly prolonged renal allograft survival compared with WT controls. IL-6 protein was upregulated in renal tubules and endothelium of renal allografts following rejection, which correlated with an increase in serum IL-6 compared with that in those receiving KO grafts or naive controls. The absence of graft-producing IL-6 or lower levels of serum IL-6 in the recipients receiving IL-6 KO allografts was associated with decreased circulating anti-graft alloantibodies and increased the percentage of intragraft CD4(+)CD25(+)Foxp3(+) Treg cells compared with those with WT allografts. In conclusion, the lack of graft-producing IL-6 significantly prolongs renal allograft survival, which is associated with reduced alloantibody production and/or increased intragraft Treg cell population, implying that targeting donor IL-6 may effectively prevent both humoral and cellular rejection of kidney transplants.

  3. The interplay between cyclic AMP and insulin during obesity development

    DEFF Research Database (Denmark)

    Borkowski, Kamil

    Insulin and cAMP signalling are related to two opposite metabolic responses. Insulin secretion is elicited in response to food availability and trigger catabolic processes like lipogenesis and glycogen synthesis with a purpose of energy storage. On the other hand cAMP signalling is associated wit...

  4. Novel cAMP targets in cell proliferation

    NARCIS (Netherlands)

    Kuiperij, Hinke Bertha


    cAMP is a second messenger that plays a role in a wide variety of biological processes, one of which is the regulation of cell proliferation. Adenylate cyclases generate cAMP in the cell upon activation, followed by binding to and activation of its direct targets, PKA and Epac. PKA is a protein kina

  5. Design of a Sapling Branch Grafting Robot

    Directory of Open Access Journals (Sweden)

    Qun Sun


    Full Text Available The automatic sapling grafting methods and grafting robot technologies are not comprehensively studied despite the fact that they are urgently required in practice. For this reason, a sapling grafting robot is developed to implement automatic grafting for saplings. The developed grafting robot includes clipping mechanism, moving mechanism, cutting mechanism, binding mechanism, and Arduino MCU based control system, which is capable of clipping, moving, positioning, cutting, grafting, and binding saplings. Experiments show that the stock cutting efficiency is 98.4%, the scion cutting efficiency is 98.9%, the grafting efficiency is 87.3%, and the binding efficiency is 68.9%.

  6. Endovascular Therapy is Effective Treatment for Focal Stenoses in Failing Infrapopliteal Vein Grafts (United States)

    Westin, Gregory G.; Armstrong, Ehrin J.; Javed, Usman; Balwanz, Christopher R.; Saeed, Haseeb; Pevec, William C.; Laird, John R.; Dawson, David L.


    endovascular interventions to restore or prolong graft patency may be associated with maintained graft patency and that close follow up with vascular laboratory surveillance is essential. PMID:25106106

  7. Balloon Tamponade Treatment of a Stent-graft Related Rupture with a Splenic Artery Pseudoaneurysm: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, See Hyung; Kim, Young Hwan [Dongsan Medical Center, Keimyung University College of Medicine, Daegu (Korea, Republic of)


    An arterial rupture resulting from stent-graft placement of a splenic artery pseudoaneurysm is a life-threatening complication and immediate endovascular or surgical treatment is indicated. We report a case of a stentgraft related splenic artery rupture treated solely with a prolonged balloon catheter tamponade, which resulted in preservation of vessel patency

  8. Prognostic factors for perioperative myocardial infarction and immediate mortality in patients who underwent coronary artery bypass graft surgery

    Directory of Open Access Journals (Sweden)

    Mirtha López Ramírez


    Conclusions: Older age and higher body mass index were protective prognostic factors for perioperative acute myocardial infarction events. Prolonged surgical time and complications were independently associated with perioperative infarction and mortality after coronary artery bypass graft surgery. Low preoperative glomerular filtration rate was also associated with mortality.

  9. MEK Inhibitors Reverse cAMP-Mediated Anxiety in Zebrafish

    DEFF Research Database (Denmark)

    Lundegaard, Pia R.; Anastasaki, Corina; Grant, Nicola J.;


    Altered phosphodiesterase (PDE)-cyclic AMP (cAMP) activity is frequently associated with anxiety disorders, but current therapies act by reducing neuronal excitability rather than targeting PDE-cAMP-mediated signaling pathways. Here, we report the novel repositioning of anti-cancer MEK inhibitors...... as anxiolytics in a zebrafish model of anxiety-like behaviors. PDE inhibitors or activators of adenylate cyclase cause behaviors consistent with anxiety in larvae and adult zebrafish. Small-molecule screening identifies MEK inhibitors as potent suppressors of cAMP anxiety behaviors in both larvae and adult...... zebrafish, while causing no anxiolytic behavioral effects on their own. The mechanism underlying cAMP-induced anxiety is via crosstalk to activation of the RAS-MAPK signaling pathway. We propose that targeting crosstalk signaling pathways can be an effective strategy for mental health disorders, and advance...

  10. 8-Chloro-cAMP-Related Changes on Mice Uteri

    Directory of Open Access Journals (Sweden)

    Andrea Actis


    Full Text Available Histopathological effects of cAMP analog (8-Chloro-cAMP, tamoxifen, and medroxyprogesterone, alone or combined, upon BALB/c mice uteri are reported. 8-Chloro-cAMP diminished uterine weight, but did not modify its histopathology or estral cycle significantly. Tamoxifen diminished uterine weight showing cystic hyperplasia and an estral cycle arrested at diestrus. Medroxyprogesterone increased uterine weight, caused a swelling of the endometrium and a pseudopregnancy estrus. When combined with 8-Chloro-cAMP, tamoxifen or medroxyprogesterone always had a predominant effect. We concluded that the effects of 8-Chloro-cAMP on mice uteri did not cause significant changes on its histopathology, but diminished its weight.

  11. Control of bacterial exoelectrogenesis by c-AMP-GMP. (United States)

    Nelson, James W; Sudarsan, Narasimhan; Phillips, Grace E; Stav, Shira; Lünse, Christina E; McCown, Phillip J; Breaker, Ronald R


    Major changes in bacterial physiology including biofilm and spore formation involve signaling by the cyclic dinucleotides c-di-GMP and c-di-AMP. Recently, another second messenger dinucleotide, c-AMP-GMP, was found to control chemotaxis and colonization by Vibrio cholerae. We have identified a superregulon of genes controlled by c-AMP-GMP in numerous Deltaproteobacteria, including Geobacter species that use extracellular insoluble metal oxides as terminal electron acceptors. This exoelectrogenic process has been studied for its possible utility in energy production and bioremediation. Many genes involved in adhesion, pilin formation, and others that are important for exoelectrogenesis are controlled by members of a variant riboswitch class that selectively bind c-AMP-GMP. These RNAs constitute, to our knowledge, the first known specific receptors for c-AMP-GMP and reveal that this molecule is used by many bacteria to control specialized physiological processes.

  12. Quality of drug label information on QT interval prolongation

    DEFF Research Database (Denmark)

    Warnier, Miriam J; Holtkamp, Frank A; Rutten, Frans H;


    characteristics (SPC) of recently approved medicinal products. METHODS: Drug labels of products centrally approved in Europe between 2006 and 2012 were screened. Of drugs including the term 'QT' in the SPC, the message on QT-prolongation ('no prolongation'/'unclear drug-QT association'/'possibly QT......-prolongation'/'QT-prolongation') and the advice on cautionary measures pertaining to QT-prolongation in the label were examined, as well as their association. RESULTS: Of the 175 screened products, 44 contained information on QT in the SPC ('no QT-prolongation': 23%, 'unclear drug-QT association': 43%, 'possibly QT-prolongation': 16%, 'QT......-prolongation': 18%). 62% contained advices to act with caution in patients with additional risk factors for QT-prolongation. Products that more likely to have QT-prolonging properties according to the SPC provided more information on QT-prolongation in the SPC ('no prolongation': 10% and for the category 'QT...

  13. Left Ventricular Function After Prolonged Exercise in Equine Endurance Athletes

    DEFF Research Database (Denmark)

    Flethøj, M.; Schwarzwald, C. C.; Haugaard, M. M.;


    Background: Prolonged exercise in human athletes is associated with transient impairment of left ventricular (LV) function, known as cardiac fatigue. Cardiac effects of prolonged exercise in horses remain unknown. Objectives :To investigate the effects of prolonged exercise on LV systolic...

  14. Influence of Increasing Load on Rat Myocardial ATP, AMP and AMP/ATP%递增负荷对大鼠心肌ATP、AMP及AMP/ATP的影响

    Institute of Scientific and Technical Information of China (English)



    为了探讨逐级递增跑台运动训练方式对大鼠心肌ATP、AMP及AMP/ATP的影响,建立了逐级递增跑台运动训练动物模型,采用高效液相色谱检测AMP、ATP的含量.研究结果表明:随着运动负荷的增加,大鼠心肌AMP含量呈现上升趋势,与对照组相比较,存在显著性差异(P<0.05);ATP含量呈现先下降趋势,存在显著性差异(P<0.05),后期出现的轻微上升趋势没有显著性差异(P>0.05);ATP/AMP呈现上升趋势,存在显著性差异(P<0.05).大鼠心肌对于逐级递增运动呈现适应性强度,运动过程中AMP/ATP比值的改变是ATP与AMP综合变化的效应,ATP变化幅度还是非常的有限,主要是通过增加AMP含量来提升能量供应.%To investigate the influence of the incremental treadmill exercise training on the rat cardiomyocytes ATP,AMP and AMP/ATP 's ,a model of incremental treadmill exercise training for animals was built. High-performance liquid chromatography was used to detect AMP, ATP content. The results:show that with the increase in exercise load, AMP content of rat cardiac increases. Compared with the control group, there was a significant difference (P0. 05) ;with ATP / AMP rising, there was a significant difference (P<0. 05). It can be concluded that the myocardial show adaptability to the intensity of incremental movement. Although the change in the ratio of AMP to ATP results from the change of ATP and AMP, the ATP's variation is limited,mainly by increasing the AMP content to supply energy.

  15. Vascular graft infections with Mycoplasma

    DEFF Research Database (Denmark)

    Levi-Mazloum, Niels Donald; Skov Jensen, J; Prag, J;


    Vascular graft infection is one of the most serious complications in vascular surgery. It is associated with mortality rates ranging from 25% to 75% and with morbidity in the form of amputation in approximately 30% of patients. Staphylococcus aureus is the leading pathogen. With conventional...... laboratory techniques, the percentage of culture-negative yet grossly infected vascular grafts seems to be increasing and is not adequately explained by the prior use of antibiotics. We have recently reported the first case of aortic graft infection with Mycoplasma. We therefore suggest the hypothesis...... that the large number of culture-negative yet grossly infected vascular grafts may be due to Mycoplasma infection not detected with conventional laboratory technique....

  16. Counteracting roles of AMP deaminase and AMP kinase in the development of fatty liver.

    Directory of Open Access Journals (Sweden)

    Miguel A Lanaspa

    Full Text Available Fatty liver (hepatic steatosis is associated with nucleotide turnover, loss of ATP and generation of adenosine monophosphate (AMP. It is well known that in fatty liver, activity of the AMP-activated kinase (AMPK is reduced and that its stimulation can prevent hepatic steatosis by both enhancing fat oxidation and reducing lipogenesis. Here we show that another AMP dependent enzyme, AMPD2, has opposing effects on fatty acid oxidation when compared to AMPK. In human hepatocytres, AMPD2 activation -either by overexpression or by lowering intracellular phosphate levels with fructose- is associated with a significant reduction in AMPK activity. Likewise, silencing of AMPK spontaneously increases AMPD activity, demonstrating that these enzymes counter-regulate each other. Furthermore, we show that a downstream product of AMP metabolism through AMPD2, uric acid, can inhibit AMPK activity in human hepatocytes. Finally, we show that fructose-induced fat accumulation in hepatocytes is due to a dominant stimulation of AMPD2 despite stimulating AMPK. In this regard, AMPD2-deficient hepatocytes demonstrate a further activation of AMPK after fructose exposure in association with increased fatty acid oxidation, and conversely silencing AMPK enhances AMPD-dependent fat accumulation. In vivo, we show that sucrose fed rats also develop fatty liver that is blocked by metformin in association with both a reduction in AMPD activity and an increase in AMPK activity. In summary, AMPD and AMPK are both important in hepatic fat accumulation and counter-regulate each other. We present the novel finding that uric acid inhibits AMPK kinase activity in fructose-fed hepatocytes thus providing new insights into the pathogenesis of fatty liver.

  17. 鲍曼不动杆菌AmpC酶和AmpC耐药基因检测分析%Detection on AmpC b-lactamases and AmpC gene of Acinetobacter baumannii

    Institute of Scientific and Technical Information of China (English)

    张丽梅; 苏丹虹; 徐韫健


    目的 检测临床分离的45株鲍曼不动杆菌的AmpC酶和AmpC耐药基因,并探讨产AmpC酶菌株的耐药情况.方法 采用超声破碎法提取45株细菌的β-内酰胺酶粗提物,进行三维试验,提取45株细菌的总DNA,聚合酶链反应(PCR)扩增AmpC结构基因和ACT-1、CMY-G1、CMY-G2、DHA、FOX耐药基因,最低抑菌浓度药物敏感试验分析菌株的耐药性.结果 45株鲍曼不动杆菌中三维试验和PCR检测AmpC基因同时阳性的有11株,确认产AmpC酶菌株为11株.三维试验方法和PCR基因检测方法比较对AmpC酶的检出率差异无统计学意义(χ2=3.500,P>0.05).ACT-1的检出率为4.4%,未检出FOX 、DHA、CMY-G1、CMY-G2.产AmpC酶菌株的药物敏感度最高是丁胺卡那霉素(90.9%),其次是亚胺培南(54.5%),产AmpC酶菌株耐药率高,对氨苄西林、氨曲南、头孢曲松、头孢替坦、头孢唑啉、呋喃妥因、头孢他啶达到100.0%,产AmpC酶菌株对抗菌药物的耐药性显著高于不产AmpC酶菌株.结论 三维试验方法和PCR基因检测方法对AmpC酶的检出率无明显差别,但仍存在假阳性与假阴性.产AmpC酶菌株耐药情况严重,提示临床应慎重用药.

  18. Femorofemoral grafts for lower limb ischemia caused by intra-aortic balloon pump. (United States)

    Friedell, M L; Alpert, J; Parsonnet, V; Brief, D K; Brener, B J; Goldenkranz, R J; Nozick, J


    From January 1975 to December 1985, 1454 patients had an intra-aortic balloon inserted for cardiac assistance. Eighty balloon-dependent patients had severe limb ischemia and required a femorofemoral graft (FFG) (5% of the total group of patients). Twenty-nine of the 80 patients with grafts (or 36%) left the hospital and 28 were followed up for an average of 40 months to determine late complications associated with the crossover grafts. All grafts remained patent. The 28 patients were classified into five groups according to the degree and type of lower limb ischemia. Group I consisted of 13 asymptomatic patients (46%); group II had four (14%) patients with mild claudication caused by preexisting peripheral arteriosclerosis; group III comprised four patients (14%) without preexisting disease but claudication subsequent to the FFG; group IV had five patients with irreversible ischemic sequelae before grafting ending in amputation, foot drop, or persistent paresthesia; and group V consisted of two patients with graft infection (7%). The perioperative mortality rate of the balloon-dependent patients with an FFG (64%) reflects the gravity of the cardiac condition. Placement of an FFG to relieve limb ischemia in these patients is followed by few immediate or late complications in the survivors and any persistent limb changes were related to the prolonged ischemia present before revascularization. Our data suggest that in balloon-dependent patients with limb-threatening ischemia, aggressive use of the FFG is limb-saving, durable, and allows continuation of balloon support.

  19. Prolonged acute hepatitis A mimicking autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    Rintaro Mikata; Osamu Yokosuka; Fumio Imazeki; Kenichi Fukai; Tatsuo Kanda; Hiromitsu Saisho


    AIM: We report a case with a prolonged course of hepatitisA, with alanine aminotransferase (ALT) higher than 500 IU/Lfor more than 2 mo.METHODS: A middle-aged woman had an elevated IgG level of more than 2 000 mg/dL, positive arti-nudear antibodies (ANA) and anti-smooth muscle antibodies (ASMA), but no evidence of persistent hepatitis A virus (HAV) infection. Liver biopsy findings were compatible with prolonged acute hepatitis, although acute onset of autoimmune hepatitis could not be ruled out.RESULTS: It was assumed that she developed a course of hepatitis similar to autoimmune hepatitis triggered by HAV infection. Ursodeoxycholic acid (UDCA) treatment was initiated and a favorable outcome was obtained. CONCLUSION: We describe a case of a middle-aged woman who showed a prolonged course of acute hepatitis A mimicking autoimmune hepatitis. Treatment with UDCAproved to be effective.

  20. Sequential Vein Bypass Grafting is Not Associated with an Increase of Either In-hospital or Mid-term Adverse Events in Off-pump Coronary Artery Bypass Grafting

    Institute of Scientific and Technical Information of China (English)

    Fucheng Xiao; Jian Wang; Hengchao Wu; Hansong Sun


    Background:The impact of sequential vein bypass grafting on clinical outcomes is less known in off-pump coronary artery bypass grafting (CABG).We aimed to evaluate the effects of sequential vein bypass grafting on clinical outcomes in off-pump CABG.Methods:From October 2009 to September 2013 at the Fuwai Hospital,127 patients with at least one sequential venous graft were matched with 127 patients of individual venous grafts only,using propensity score matching method to obtain risk-adjusted outcome comparison.In-hospital measurement was composite outcome of in-hospital death,myocardial infarction (MI),stroke,requirement for intra-aortic ballon pump (IABP) assistance and prolonged ventilation.Major adverse cardiac events (MACEs:Death,MI or repeat revascularization) and angina recurrence were considered as mid-term endpoints.Results:No significant difference was observed among the groups in baseline characteristics.Intraoperative mean blood flow per vein graft was 40.4 ml in individual venous grafts groups versus 59.5 ml in sequential venous grafts groups (P < 0.001).There were no differences between individual and sequential venous grafts groups with regard to composite outcome of in-hospital mortality,MI,stroke,IABP assistance and prolonged ventilation (11.0% vs.14.2%,P =0.45).Individual in-hospital measurement also did not differ significantly between the two groups.At about four years follow-up,the survival estimates free from MACEs (92.5% vs.97.3%,P =0.36) and survival rates free of angina recurrence (80.9% vs.85.5%,P =0.48) were similar among individual and sequential venous grafts groups with a mean follow-up of 22.5 months.In the Cox regression analysis,sequential vein bypass grafting was not identified as an independent predictor of both MACEs and angina recurrence.Conclusions:Compared to individual vein bypass grafting,sequential vein bypass grafting was not associated with an increase of either in-hospital or mid-term adverse events in

  1. The Popeye Domain Containing Genes and cAMP Signaling

    Directory of Open Access Journals (Sweden)

    Thomas Brand


    Full Text Available 3'-5'-cyclic adenosine monophosphate (cAMP is a second messenger, which plays an important role in the heart. It is generated in response to activation of G-protein-coupled receptors (GPCRs. Initially, it was thought that protein kinase A (PKA exclusively mediates cAMP-induced cellular responses such as an increase in cardiac contractility, relaxation, and heart rate. With the identification of the exchange factor directly activated by cAMP (EPAC and hyperpolarizing cyclic nucleotide-gated (HCN channels as cAMP effector proteins it became clear that a protein network is involved in cAMP signaling. The Popeye domain containing (Popdc genes encode yet another family of cAMP-binding proteins, which are prominently expressed in the heart. Loss-of-function mutations in mice are associated with cardiac arrhythmia and impaired skeletal muscle regeneration. Interestingly, the cardiac phenotype, which is present in both, Popdc1 and Popdc2 null mutants, is characterized by a stress-induced sinus bradycardia, suggesting that Popdc proteins participate in cAMP signaling in the sinuatrial node. The identification of the two-pore channel TREK-1 and Caveolin 3 as Popdc-interacting proteins represents a first step into understanding the mechanisms of heart rate modulation triggered by Popdc proteins.

  2. Safety information on QT-interval prolongation

    DEFF Research Database (Denmark)

    Warnier, Miriam J; Holtkamp, Frank A; Rutten, Frans H;


    Prolongation of the QT interval can predispose to fatal ventricular arrhythmias. Differences in QT-labeling language can result in miscommunication and suboptimal risk mitigation. We systematically compared the phraseology used to communicate on QT-prolonging properties of 144 drugs newly approve......) was moderate (kappa 0.434). However, the agreement in expected clinical decisions based on the product labels was much higher (kappa 0.673). The US drug label tends to be more explicit, especially when it considers absence of QT effects....

  3. Prolonged heart xenograft survival using combined total lymphoid irradiation and cyclosporine

    Energy Technology Data Exchange (ETDEWEB)

    Knechtle, S.J.; Halperin, E.C.; Saad, T.; Bollinger, R.R.


    Total lymphoid irradiation and cyclosporine have profound immunosuppressive properties and permit successful heart allotransplantation. Cyclosporine used alone has not permitted consistently successful transplantation between species in all cases. Total lymphoid irradiation has not been applied to xenotransplantation. The efficacy of total lymphoid irradiation alone and in combination with cyclosporine was examined using an animal model of heart xenotransplantation. Heterotopic heart transplants were performed using inbred Syrian hamsters as donors and Lewis rats as recipients. Total lymphoid irradiation was administered preoperatively over 3 weeks for a total dose of 15 gray. Cyclosporine was started on the day of surgery and was given as a daily intramuscular injection of 2.5, 5, or 10 mg/kg/day until rejection was complete. Neither total lymphoid irradiation nor cyclosporine alone markedly prolonged graft survival. However, combined total lymphoid irradiation and cyclosporine, 5 or 10 mg/kg/day, dramatically prolonged graft survival to greater than 100 days in most recipients. There were no treatment-related deaths. In conclusion, combined total lymphoid irradiation and cyclosporine permit successful long-term survival of heart xenotransplants in this hamster-to-rat model.

  4. Imaging alterations of cardiomyocyte cAMP microdomains in disease

    Directory of Open Access Journals (Sweden)

    Alexander eFroese


    Full Text Available 3’,5’-cyclic adenosine monophosphate (cAMP is an important second messenger which regulates heart function by acting in distinct subcellular microdomains. Recent years have provided deeper mechanistic insights into compartmentalized cAMP signaling and its link to cardiac disease. In this mini review, we summarize newest developments in this field achieved by cutting-edge biochemical and biophysical techniques. We further compile the data from different studies into a bigger picture of so far uncovered alterations in cardiomyocyte cAMP microdomains which occur in compensated cardiac hypertrophy and chronic heart failure. Finally, future research directions and translational perspectives are briefly discussed.

  5. Endovascular aortic graft infection resulting in retroperitoneal abscess: report of a case

    Directory of Open Access Journals (Sweden)

    Salvatore Di Somma


    Full Text Available Infection is a rare complication of aortoiliac endovascular procedures, with an incidence inferior to 0.5%, and it may result in a retroperitoneal abscess potentially evolving to sepsis and gastrointestinal bleeding. In more than 50% of cases endovascular aortoiliac prosthetic grafts infection occur months or years after the procedure. The growing number of endovascular procedures, and as the actually midterm follow up in most cases, septic sequelae will no doubt continue to occur with increased frequency and may represent an emerging problem in the ED for the emergency physician. Endovascular graft infection begins with unspecific clinical manifestations. An high index of suspicion in any patient with an aortic stent graft presenting prolonged or recurrent fever and or abdominal or back pain and a low threshold for obtaining CT scan should increase the clinician’s ability to make a timely diagnosis in the ED setting.

  6. Hydrogen Gas Ameliorates Hepatic Reperfusion Injury After Prolonged Cold Preservation in Isolated Perfused Rat Liver. (United States)

    Shimada, Shingo; Wakayama, Kenji; Fukai, Moto; Shimamura, Tsuyoshi; Ishikawa, Takahisa; Fukumori, Daisuke; Shibata, Maki; Yamashita, Kenichiro; Kimura, Taichi; Todo, Satoru; Ohsawa, Ikuroh; Taketomi, Akinobu


    Hydrogen gas reduces ischemia and reperfusion injury (IRI) in the liver and other organs. However, the precise mechanism remains elusive. We investigated whether hydrogen gas ameliorated hepatic I/R injury after cold preservation. Rat liver was subjected to 48-h cold storage in University of Wisconsin solution. The graft was reperfused with oxygenated buffer with or without hydrogen at 37° for 90 min on an isolated perfusion apparatus, comprising the H2 (+) and H2 (-) groups, respectively. In the control group (CT), grafts were reperfused immediately without preservation. Graft function, injury, and circulatory status were assessed throughout the perfusion. Tissue samples at the end of perfusion were collected to determine histopathology, oxidative stress, and apoptosis. In the H2 (-) group, IRI was indicated by a higher aspartate aminotransferase (AST), alanine aminotransferase (ALT) leakage, portal resistance, 8-hydroxy-2-deoxyguanosine-positive cell rate, apoptotic index, and endothelial endothelin-1 expression, together with reduced bile production, oxygen consumption, and GSH/GSSG ratio (vs. CT). In the H2 (+) group, these harmful changes were significantly suppressed [vs. H2 (-)]. Hydrogen gas reduced hepatic reperfusion injury after prolonged cold preservation via the maintenance of portal flow, by protecting mitochondrial function during the early phase of reperfusion, and via the suppression of oxidative stress and inflammatory cascades thereafter.

  7. Multiple Facets of cAMP Signalling and Physiological Impact: cAMP Compartmentalization in the Lung

    Directory of Open Access Journals (Sweden)

    Martina Schmidt


    Full Text Available Therapies involving elevation of the endogenous suppressor cyclic AMP (cAMP are currently used in the treatment of several chronic inflammatory disorders, including chronic obstructive pulmonary disease (COPD. Characteristics of COPD are airway obstruction, airway inflammation and airway remodelling, processes encompassed by increased airway smooth muscle mass, epithelial changes, goblet cell and submucosal gland hyperplasia. In addition to inflammatory cells, airway smooth muscle cells and (myofibroblasts, epithelial cells underpin a variety of key responses in the airways such as inflammatory cytokine release, airway remodelling, mucus hypersecretion and airway barrier function. Cigarette smoke, being next to environmental pollution the main cause of COPD, is believed to cause epithelial hyperpermeability by disrupting the barrier function. Here we will focus on the most recent progress on compartmentalized signalling by cAMP. In addition to G protein-coupled receptors, adenylyl cyclases, cAMP-specific phospho-diesterases (PDEs maintain compartmentalized cAMP signalling. Intriguingly, spatially discrete cAMP-sensing signalling complexes seem also to involve distinct members of the A-kinase anchoring (AKAP superfamily and IQ motif containing GTPase activating protein (IQGAPs. In this review, we will highlight the interaction between cAMP and the epithelial barrier to retain proper lung function and to alleviate COPD symptoms and focus on the possible molecular mechanisms involved in this process. Future studies should include the development of cAMP-sensing multiprotein complex specific disruptors and/or stabilizers to orchestrate cellular functions. Compartmentalized cAMP signalling regulates important cellular processes in the lung and may serve as a therapeutic target.

  8. Prolonged Cholestatic Jaundice Associated With Flurbiprofen. (United States)

    Dogan, Serkan; Celikbilek, Mehmet; Demirkan, Kutay; Yilmaz, Semih; Deniz, Kemal; Gursoy, Sebnem; Yucesoy, Mehmet


    Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely consumed drugs throughout the world for pain relief. Although the adverse effects of NSAIDs to the liver are well known, flurbiprofen-induced liver cholestasis is extremely rare. Herein, we present a patient with prolonged icterus that is associated with the use of flurbiprofen without causing ductopenia.

  9. Amped Up! - Volume 1, No. 3, May/June 2015

    Energy Technology Data Exchange (ETDEWEB)



    Welcome to the latest issue of our bimonthly newsletter, Amped Up!, highlighting the initiatives, events and technologies in the Office of Energy Efficiency and Renewable Energy that influence change.

  10. Cardiac cAMP: production, hydrolysis, modulation and detection

    Directory of Open Access Journals (Sweden)

    Cédric eBOULARAN


    Full Text Available Cyclic adenosine 3’,5’-monophosphate (cAMP modulates a broad range of biological processes including the regulation of cardiac myocyte contractile function where it constitutes the main second messenger for β-adrenergic receptors’ signaling to fulfill positive chronotropic, inotropic and lusitropic effects. A growing number of studies pinpoint the role of spatial organization of the cAMP signaling as an essential mechanism to regulate cAMP outcomes in cardiac physiology. Here, we will briefly discuss the complexity of cAMP synthesis and degradation in the cardiac context, describe the way to detect it and review the main pharmacological arsenal to modulate its availability.

  11. Toxoplasma gondii Cyclic AMP-Dependent Protein Kinase Subunit 3 Is Involved in the Switch from Tachyzoite to Bradyzoite Development

    Directory of Open Access Journals (Sweden)

    Tatsuki Sugi


    Full Text Available Toxoplasma gondii is an obligate intracellular apicomplexan parasite that infects warm-blooded vertebrates, including humans. Asexual reproduction in T. gondii allows it to switch between the rapidly replicating tachyzoite and quiescent bradyzoite life cycle stages. A transient cyclic AMP (cAMP pulse promotes bradyzoite differentiation, whereas a prolonged elevation of cAMP inhibits this process. We investigated the mechanism(s by which differential modulation of cAMP exerts a bidirectional effect on parasite differentiation. There are three protein kinase A (PKA catalytic subunits (TgPKAc1 to -3 expressed in T. gondii. Unlike TgPKAc1 and TgPKAc2, which are conserved in the phylum Apicomplexa, TgPKAc3 appears evolutionarily divergent and specific to coccidian parasites. TgPKAc1 and TgPKAc2 are distributed in the cytomembranes, whereas TgPKAc3 resides in the cytosol. TgPKAc3 was genetically ablated in a type II cyst-forming strain of T. gondii (PruΔku80Δhxgprt and in a type I strain (RHΔku80Δhxgprt, which typically does not form cysts. The Δpkac3 mutant exhibited slower growth than the parental and complemented strains, which correlated with a higher basal rate of tachyzoite-to-bradyzoite differentiation. 3-Isobutyl-1-methylxanthine (IBMX treatment, which elevates cAMP levels, maintained wild-type parasites as tachyzoites under bradyzoite induction culture conditions (pH 8.2/low CO2, whereas the Δpkac3 mutant failed to respond to the treatment. This suggests that TgPKAc3 is the factor responsible for the cAMP-dependent tachyzoite maintenance. In addition, the Δpkac3 mutant had a defect in the production of brain cysts in vivo, suggesting that a substrate of TgPKAc3 is probably involved in the persistence of this parasite in the intermediate host animals.

  12. Analogs of Cyclic AMP as Chemoattractants and Inhibitors of Dictyostelium Chemotaxis

    NARCIS (Netherlands)

    Haastert, Peter J.M. van; Jastorff, Bernd; Pinas, Johan E.; Konijn, Theo M.


    Aggregative amoebae of Dictyostelium discoideum, D. mucoroides, D. purpureum, and D. rosarium react chemotactically to cyclic AMP (cAMP). We measured the chemotactic activity of 14 cAMP analogs and found that these four species have a similar sensitivity to chemical modifications of cAMP; this sugge

  13. CMOS technology and current-feedback op-amps

    DEFF Research Database (Denmark)

    Bruun, Erik


    Some of the problems related to the application of CMOS technology to current-feedback operational amplifiers (CFB op-amps) are identified. Problems caused by the low device transconductance and by the absence of matching between p-channel and n-channel transistors are examined, and circuit...... poor performance compared to the bipolar designs, but CMOS has a potential for CFB op-amp design if more ingenious circuit configurations are applied...

  14. Microgravity changes in heart structure and cyclic-AMP metabolism (United States)

    Philpott, D. E.; Fine, A.; Kato, K.; Egnor, R.; Cheng, L.


    The effects of microgravity on cardiac ultrastructure and cyclic AMP metabolism in tissues of rats flown on Spacelab 3 are reported. Light and electron microscope studies of cell structure, measurements of low and high Km phosphodiesterase activity, cyclic AMP-dependent protein kinase activity, and regulatory subunit compartmentation show significant deviations in flight animals when compared to ground controls. The results indicate that some changes have occurred in cellular responses associated with catecholamine receptor interactions and intracellular signal processing.

  15. Allostery and conformational dynamics in cAMP-binding acyltransferases. (United States)

    Podobnik, Marjetka; Siddiqui, Nida; Rebolj, Katja; Nambi, Subhalaxmi; Merzel, Franci; Visweswariah, Sandhya S


    Mycobacteria harbor unique proteins that regulate protein lysine acylation in a cAMP-regulated manner. These lysine acyltransferases from Mycobacterium smegmatis (KATms) and Mycobacterium tuberculosis (KATmt) show distinctive biochemical properties in terms of cAMP binding affinity to the N-terminal cyclic nucleotide binding domain and allosteric activation of the C-terminal acyltransferase domain. Here we provide evidence for structural features in KATms that account for high affinity cAMP binding and elevated acyltransferase activity in the absence of cAMP. Structure-guided mutational analysis converted KATms from a cAMP-regulated to a cAMP-dependent acyltransferase and identified a unique asparagine residue in the acyltransferase domain of KATms that assists in the enzymatic reaction in the absence of a highly conserved glutamate residue seen in Gcn5-related N-acetyltransferase-like acyltransferases. Thus, we have identified mechanisms by which properties of similar proteins have diverged in two species of mycobacteria by modifications in amino acid sequence, which can dramatically alter the abundance of conformational states adopted by a protein.

  16. Prevention of primary vascular graft infection with silver-coated polyester graft in a porcine model

    DEFF Research Database (Denmark)

    Gao, H; Sandermann, J; Prag, J;


    To evaluate the efficacy of a silver-coated vascular polyester graft in the prevention of graft infection after inoculation with Staphylococcus aureus in a porcine model.......To evaluate the efficacy of a silver-coated vascular polyester graft in the prevention of graft infection after inoculation with Staphylococcus aureus in a porcine model....

  17. ^amp;+^amp;-p Electroproduction Cross Sections off Protons in the Second Resonance Region (United States)

    Fedotov, Gleb; Gothe, Ralf; Mokeev, Victor


    In this talk we present preliminary ^amp;+^amp;-p electroproduction cross sections off protons in the kinematical area of W from 1.4 to 1.8 GeV and Q^2 from 0.4 to 1.1 GeV^2. Our kinematical coverage in part overlap with previous CLAS measurements, but offers more than a factor six finer binning in Q^2. The physics analysis of these data within the framework of the JM model will allow us to determine the electrocouplings and the partial πδ, ρp decay widths of several high lying nucleon resonances S31(1620), S11(1650), F15(1685), D33(1700), P13(1720) and to further explore the evidence for the 3/2^+(1720) candidate-state. Analysis of the single pion electroproduction data measured with CLAS in the aforementioned kinematic region is in progress. Single and charged double pion exclusive channels are major contributors to the meson electroproduction in the N* excitation region with different non-resonant mechanisms. A successful description of all observables in these exclusive channels with consistent N* electrocouplings will offer evidence for the reliable evaluation of these fundamental quantities.

  18. Analogs of cyclic AMP as chemoattractants and inhibitors of Dictyostelium chemotaxis. (United States)

    Van Haastert, P J; Jastorff, B; Pinas, J E; Konijn, T M


    Aggregative amoebae of Dictyostelium discoideum, D. mucoroides, D. purpureum, and D. rosarium react chemotactically to cyclic AMP (cAMP). We measured the chemotactic activity of 14 cAMP analogs and found that these four species have a similar sensitivity to chemical modifications of cAMP; this suggests that the cAMP receptor is identical in all of these species. Besides the induction of a chemotactic response, cAMP analogs also may delay or prevent cell aggregation. cAMP analogs like N1-O-cAMP, 2'-H-cAMP, and 5'NH-cAMP are chemotactically nearly as active as cAMP and induced no, or only a short, delay of cell aggregation. Other cAMP derivatives, such as 6-Cl-cPMP and 8-Br-cAMP, are chemotactically active only at high concentrations and delayed cell aggregation for several hours. Still other cAMP analogs, which do not induce a chemotactic reaction in D. mucoroides, D. purpureum, and D. rosarium, either prevented cell aggregation [cAMPS(S), cAMPS(R), and 3'-NH-cAMP[ or had no effect on cell aggregation [cAMPN(CH3)2(S) and cAMPN(CH3)2(R)]. cAMP analog 3'-NH-cAMP prevented cell aggregation by the inhibition of chemotaxis, whereas cell locomotion was not affected. Although we cannot provide a satisfactory explantation for these observations, our data suggest that occupation and activation of the cAMP receptors do not always induced a chemotactic response.

  19. The CytR repressor antagonizes cyclic AMP-cyclic AMP receptor protein activation of the deoCp2 promoter of Escherichia coli K-12

    DEFF Research Database (Denmark)

    Søgaard-Andersen, L; Martinussen, J; Møllegaard, N E;


    We have investigated the regulation of the Escherichia coli deoCp2 promoter by the CytR repressor and the cyclic AMP (cAMP) receptor protein (CRP) complexed to cAMP. Promoter regions controlled by these two proteins characteristically contain tandem cAMP-CRP binding sites. Here we show that (i) Cyt......R selectively regulated cAMP-CRP-dependent initiations, although transcription started from the same site in deoCp2 in the absence or presence of cAMP-CRP; (ii) deletion of the uppermost cAMP-CRP target (CRP-2) resulted in loss of CytR regulation, but had only a minor effect on positive control by the cAMP...

  20. Severe bradycardia and prolonged hypotension in ciguatera. (United States)

    Chan, Thomas Yan Keung


    Ciguatera results when ciguatoxin-contaminated coral reef fish from tropical or subtropical waters are consumed. The clinical features that present in affected persons are mainly gastrointestinal, neurological, general, and much less commonly, cardiovascular. We report the case of a 50-year-old man who developed the characteristic combination of acute gastrointestinal and neurological symptoms after the consumption of an unidentified coral reef fish head. In addition to those symptoms, he developed dizziness, severe bradycardia (46 bpm) and prolonged hypotension, which required the administration of intravenous atropine and over three days of intravenous fluid replacement with dopamine infusion. Patients with ciguatera can develop severe bradycardia and prolonged hypotension. Physicians should recognise the possible cardiovascular complications of ciguatera and promptly initiate treatment with intravenous atropine, intravenous fluid replacement and inotropic therapy if such complications are observed.


    Institute of Scientific and Technical Information of China (English)

    Song Chen; Xiao-yu Li


    Exploration and characterization of grafting productions by experimental methods are often cumbersome or sometimes impossible. Therefore, quantum chemistry calculations were performed to characterize the graft sites of epoxy resin. According to the Gibbs free energy criterion of the second law of thermodynamic, the reported graft sites were confirmed, and more important, some unreported graft sites were found. In addition, method of increasing the number of graft sites was studied in this article.

  2. 革兰阴性杆菌AmpC酶和AmpC耐药基因检测%Detection of AmpC-lactamases and AmpC gene of gram-negative bacillus

    Institute of Scientific and Technical Information of China (English)

    张丽梅; 徐韫健; 孙慧冰; 李乃健; 廖伟娇


    目的 检测革兰阴性杆菌临床分离株的AmpC酶和AmpC耐药基因,探讨产AmpC酶菌株的耐药情况.方法 用超声破碎法提取102株细菌的β-内酰胺酶粗提物,进行三维试验,提取细菌总DNA,PCR扩增ampC结构基因和ACT-1、CMY-G1、CMY-G2、DHA、FOX耐药基因,MIC法药物敏感试验分析菌株的耐药性.结果 102株革兰阴性杆菌中三维试验和PCR检测AmpC基因同时阳性的有11株,确认产AmpC酶菌株11株,并全部为鲍曼不动杆菌.三维试验和PCR基因检测AmpC酶的检出率比较,差别无统计学意义(χ2=1.125,P>0.05).ACT-1、CMY-G2、FOX、DHA、CMY-G1的检出率分别为14.7%、12.7%、4.9%、1.0%和0.对产AmpC酶菌株敏感度最高的是丁胺卡那霉素(90.1%),其次是亚胺培南(54.6%).结论 三维试验和PCR基因检测对AmpC酶的检出率无明显差别,但仍存在假阳性与假阴性.产 AmpC醇菌株耐药情况严重,提示临床慎重用药.

  3. Napping and Human Functioning during Prolonged Work (United States)


    alternative to napping is prolonged wakefulness. Polyphasic sleep , with frequent naps rather than a single sleep period per 24 hours, is natural for both the...very young and for the aged. It is not practiced by most adults, perhaps because of societal demands. Possibly a polyphasic sleep schedule could be...Functioning 1.2 Scope of this Chapter 2. REVIEW OF LITERATURE 2.1 Partial Sleep Deprivation Studies 2.2 Nap Studies: Four Nap Factors Affecting Performance

  4. Prolonged grief: setting the research agenda

    Directory of Open Access Journals (Sweden)

    Rita Rosner


    Full Text Available Background: Prolonged grief disorder is proposed for the International Classification of Diseases (ICD-11, though it was rejected as a diagnosis for DSM-5. Objective: This review outlines findings and defines important areas for future research viewed from a lifespan perspective. Results: The development and psychometric evaluation of measures for the new diagnosis is paramount, specifically for children and adolescents. Treatments need to be adapted for specific subgroups and research findings have to be disseminated into various professional settings.

  5. Polyether-polyester graft copolymer (United States)

    Bell, Vernon L. (Inventor)


    Described is a polyether graft polymer having improved solvent resistance and crystalline thermally reversible crosslinks. The copolymer is prepared by a novel process of anionic copolymerization. These polymers exhibit good solvent resistance and are well suited for aircraft parts. Previous aromatic polyethers, also known as polyphenylene oxides, have certain deficiencies which detract from their usefulness. These commercial polymers are often soluble in common solvents including the halocarbon and aromatic hydrocarbon types of paint thinners and removers. This limitation prevents the use of these polyethers in structural articles requiring frequent painting. In addition, the most popular commercially available polyether is a very high melting plastic. This makes it considerably more difficult to fabricate finished parts from this material. These problems are solved by providing an aromatic polyether graft copolymer with improved solvent resistance and crystalline thermally reversible crosslinks. The graft copolymer is formed by converting the carboxyl groups of a carboxylated polyphenylene oxide polymer to ionic carbonyl groups in a suitable solvent, reacting pivalolactone with the dissolved polymer, and adding acid to the solution to produce the graft copolymer.

  6. Prolonged ulcerative laryngitis: a new disease entity. (United States)

    Hsiao, Tzu-Yu


    Over the last decade, a new disease entity, prolonged ulcerative laryngitis (PUL), with unique clinical presentation and prolonged disease course, has been recognized. Until now, very few studies dealing with this disease have been reported in the literature. From 1999 to 2008, we analyzed clinical data from a series of 39 PUL patients who were treated with an observational approach without implementing specific treatments. This disease affects adults, predominantly females. The age of patients in our series ranged from 26 to 76 years with a median of 49.5 years. This disease is characterized by ulcers and signs of acute inflammation on the membranous portion of the vocal folds with a prolonged clinical course. The recovery times of patients ranged from 4 to 20 weeks with an average of 9.4 weeks. The data in this study may reflect a natural history of this disease. PUL seems to be a self-limited disease, but the etiology of this disease is unknown. Specific infections or systemic inflammatory processes involving the larynx must be ruled out before diagnosis, and conservative treatments are suggested.

  7. 大肠埃希菌高产AmpC酶的研究进展%Progress on AmpC hyperproduction in Escherichia coli

    Institute of Scientific and Technical Information of China (English)

    王锦娜; 邵海枫


    大肠埃希菌(E.coli)中的ampC基因与其他革兰阴性细菌不同,染色体上的ampC基因启动子与延胡索酸还原酶(frdABCD)操纵子中的frdD基因重叠,衰减子是延胡索酸还原酶操纵子的转录终止子,缺少ampC调节基因ampR,所以携带野生型基因的E.coli AmpC酶的产量非常低,临床意义不大.但近年来出现了高产AmpC酶的E. coli,对其进行研究发现,ampC基因启动子、衰减子或ampC编码区的突变,或从其他细菌获得强启动子或携带强启动子的序列插入,或从其他细菌获得调节基因ampR等都可能导致染色体型AmpC酶的高产.质粒型ampC基因在E. coli中的出现是AmpC酶高产的另一重要原因.

  8. Posterior repair with perforated porcine dermal graft

    Directory of Open Access Journals (Sweden)

    G. Bernard Taylor


    Full Text Available OBJECTIVE: To compare postoperative vaginal incision separation and healing in patients undergoing posterior repair with perforated porcine dermal grafts with those that received grafts without perforations. Secondarily, the tensile properties of the perforated and non-perforated grafts were measured and compared. MATERIALS AND METHODS: This was a non-randomized retrospective cohort analysis of women with stage II or greater rectoceles who underwent posterior repair with perforated and non-perforated porcine dermal grafts (PelvicolTM CR Bard Covington, GA USA. The incidence of postoperative vaginal incision separation (dehiscence was compared. A secondary analysis to assess graft tensile strength, suture pull out strength, and flexibility after perforation was performed using standard test method TM 0133 and ASTM bending and resistance protocols. RESULTS: Seventeen percent of patients (21/127 who received grafts without perforations developed vaginal incision dehiscence compared to 7% (5/71 of patients who received perforated grafts (p = 0.078. Four patients with vaginal incision dehiscence with non-perforated grafts required surgical revision to facilitate healing. Neither tensile strength or suture pull out strength were significantly different between perforated and non-perforated grafts (p = 0.81, p = 0.29, respectively. There was no difference in the flexibility of the two grafts (p = 0.20. CONCLUSION: Perforated porcine dermal grafts retain their tensile properties and are associated with fewer vaginal incision dehiscences.

  9. Aortic graft infection and mycotic aneurysm with Streptococcus equi zooepidemicus: two cases with favorable outcome of antibiotic treatment. (United States)

    Altreuther, Martin; Lange, Conrad; Myhre, Hans Olav; Hannula, Raisa


    Infections with Streptococcus equi zooepidemicus are rare and are associated with contact with animals or animal products. There are very few reports about infected vascular grafts or aneurysms with this etiology. We present two patients. The first is a 77-year-old man with an infected bifurcated graft four years after an open operation for an abdominal aortic aneurysm (AAA). The second is a 72-year-old man with a symptomatic mycotic AAA, treated with endovascular aneurysm repair. Both received prolonged treatment with bactericidal antibiotics and responded well. Follow-up time at present is 5.5 years for the first, and 4.5 years for the second, patient.

  10. Starch Modification by Graft Copolymerization of Acrylonitrile

    Institute of Scientific and Technical Information of China (English)

    刘瑞贤; 李莉; 茹宗玲; 张黎明; 高建平; 田汝川


    The graft copolymerization of acrylonitrile (AN) onto starch under the initiation of potassium permanganate was investigated. The effect of various reaction conditions on the graft copolymerization was studied. The relationships between the grafting rate and the initiator concentration of potassium permanganate, monomer acrylonitrile and backbone starch, as well as reaction temperature were established. The oxidation reaction of starch with manganic ions and valence changes of manganic ions during the graft copolymerization were discussed. The results show that manganic ion Mn7+ underwent a series of valence changes during the graft copolymerization: Mn(Ⅶ) → Mn(Ⅳ) → Mn(Ⅲ) → Mn(Ⅱ). The grafting rate of the graft copolymerization of acrylonitrile onto starch is also given.

  11. Dynamics of bone graft healing around implants

    Directory of Open Access Journals (Sweden)

    Narayan Venkataraman


    A few questions arise pertaining to the use of bone grafts along with implants are whether these are successful in approximation with implant. Do they accelerate bone regeneration? Are all defects ultimately regenerated with new viable bone? Is the bone graft completely resorbed or integrated in new bone? Does the implant surface characteristic positively affect osseointegration when used with a bone graft? What type of graft and implant surface can be used that will have a positive effect on the healing type and time? Finally, what are the dynamics of bone graft healing around an implant? This review discusses the cellular and molecular mechanisms of bone graft healing in general and in vicinity of another foreign, avascular body, namely the implant surface, and further, the role of bone grafts in osseointegration and/or clinical success of the implants.

  12. Postaggregative differentiation induction by cyclic AMP in Dictyostelium: intracellular transduction pathway and requirement for additional stimuli. (United States)

    Schaap, P; Van Lookeren Campagne, M M; Van Driel, R; Spek, W; Van Haastert, P J; Pinas, J


    Cyclic AMP induces postaggregative differentiation in aggregation competent cells of Dictyostelium by interacting with cell surface cAMP receptors. We investigated the transduction pathway of this response and additional requirements for the induction of postaggregative differentiation. Optimal induction of postaggregative gene expression requires that vegetative cells are first exposed to 2-4 hr of nanomolar cAMP pulses, and subsequently for 4-6 hr to steady-state cAMP concentrations in the micromolar range. Cyclic AMP pulses, which are endogenously produced before and during aggregation, induce full responsiveness to cAMP as a morphogen. The transduction pathway from the cell surface cAMP receptor to postaggregative gene expression may involve Ca2+ ions as intracellular messengers. A cAMP-induced increase in intracellular cAMP or cGMP levels is not involved in the transduction pathway.

  13. Radiation-induced grafting of diallyldimethylammonium chloride onto acrylic acid grafted polyethylene (United States)

    Francis, Sanju; Dhanawade, B. R.; Mitra, D.; Varshney, Lalit; Sabharwal, Sunil


    Diallyldimethylammonium chloride (DADMAC) was grafted onto polyethylene (PE) films by a double grafting procedure. The PE film was initially modified by grafting acrylic acid (AA), through a mutual irradiation method. AA-g-PE film, thus obtained was subjected to subsequent radiation grafting reaction of DADMAC, to give a DADMAC-g-AA-g-PE film having a comb-type structure. The influence of different conditions, such as the extent of AA grafting, DADMAC concentration, absorbed dose and dose rate, on the grafting yield of DADMAC was investigated. A maximum DADMAC grafting of 30% was achieved. The equilibrium degree of swelling (EDS) of the grafted films were gravimetrically determined. TGA and FT-IR techniques were employed to characterize the grafted PE films.

  14. Radiation-induced grafting of diallyldimethylammonium chloride onto acrylic acid grafted polyethylene

    Energy Technology Data Exchange (ETDEWEB)

    Francis, Sanju [Radiation Technology Development Section, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India)], E-mail:; Dhanawade, B.R.; Mitra, D.; Varshney, Lalit; Sabharwal, Sunil [Radiation Technology Development Section, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India)


    Diallyldimethylammonium chloride (DADMAC) was grafted onto polyethylene (PE) films by a double grafting procedure. The PE film was initially modified by grafting acrylic acid (AA), through a mutual irradiation method. AA-g-PE film, thus obtained was subjected to subsequent radiation grafting reaction of DADMAC, to give a DADMAC-g-AA-g-PE film having a comb-type structure. The influence of different conditions, such as the extent of AA grafting, DADMAC concentration, absorbed dose and dose rate, on the grafting yield of DADMAC was investigated. A maximum DADMAC grafting of 30% was achieved. The equilibrium degree of swelling (EDS) of the grafted films were gravimetrically determined. TGA and FT-IR techniques were employed to characterize the grafted PE films.

  15. AKAP18 contains a phosphoesterase domain that binds AMP. (United States)

    Gold, Matthew G; Smith, F Donelson; Scott, John D; Barford, David


    Protein kinase A anchoring proteins (AKAPs), defined by their capacity to target the cAMP-dependent protein kinase to distinct subcellular locations, function as molecular scaffolds mediating the assembly of multicomponent complexes to integrate and organise multiple signalling events. Despite their central importance in regulating cellular processes, little is known regarding their diverse structures and molecular mechanisms. Here, using bioinformatics and X-ray crystallography, we define a central domain of AKAP18 delta (AKAP18(CD)) as a member of the 2H phosphoesterase family. The domain features two conserved His-x-Thr motifs positioned at the base of a groove located between two lobes related by pseudo 2-fold symmetry. Nucleotide co-crystallisation screening revealed that this groove binds specifically to adenosine 5'-monophosphate (5'AMP) and cytosine 5'-monophosphate (5'CMP), with the affinity constant for AMP in the physiological concentration range. This is the first example of an AKAP capable of binding a small molecule. Our data generate two functional hypotheses for the AKAP18 central domain. It may act as a phosphoesterase, although we did not identify a substrate, or as an AMP sensor with the potential to couple intracellular AMP levels to PKA signalling events.

  16. Glucose Enhances Basal or Melanocortin-Induced cAMP-Response Element Activity in Hypothalamic Cells. (United States)

    Breit, Andreas; Wicht, Kristina; Boekhoff, Ingrid; Glas, Evi; Lauffer, Lisa; Mückter, Harald; Gudermann, Thomas


    Melanocyte-stimulating hormone (MSH)-induced activation of the cAMP-response element (CRE) via the CRE-binding protein in hypothalamic cells promotes expression of TRH and thereby restricts food intake and increases energy expenditure. Glucose also induces central anorexigenic effects by acting on hypothalamic neurons, but the underlying mechanisms are not completely understood. It has been proposed that glucose activates the CRE-binding protein-regulated transcriptional coactivator 2 (CRTC-2) in hypothalamic neurons by inhibition of AMP-activated protein kinases (AMPKs), but whether glucose directly affects hypothalamic CRE activity has not yet been shown. Hence, we dissected effects of glucose on basal and MSH-induced CRE activation in terms of kinetics, affinity, and desensitization in murine, hypothalamic mHypoA-2/10-CRE cells that stably express a CRE-dependent reporter gene construct. Physiologically relevant increases in extracellular glucose enhanced basal or MSH-induced CRE-dependent gene transcription, whereas prolonged elevated glucose concentrations reduced the sensitivity of mHypoA-2/10-CRE cells towards glucose. Glucose also induced CRCT-2 translocation into the nucleus and the AMPK activator metformin decreased basal and glucose-induced CRE activity, suggesting a role for AMPK/CRTC-2 in glucose-induced CRE activation. Accordingly, small interfering RNA-induced down-regulation of CRTC-2 expression decreased glucose-induced CRE-dependent reporter activation. Of note, glucose also induced expression of TRH, suggesting that glucose might affect the hypothalamic-pituitary-thyroid axis via the regulation of hypothalamic CRE activity. These findings significantly advance our knowledge about the impact of glucose on hypothalamic signaling and suggest that TRH release might account for the central anorexigenic effects of glucose and could represent a new molecular link between hyperglycaemia and thyroid dysfunction.

  17. Prolonged labour as indication for emergency caesarean section

    DEFF Research Database (Denmark)

    Maaløe, Nanna; Sorensen, B L; Onesmo, R


    To audit the quality of obstetric management preceding emergency caesarean sections for prolonged labour.......To audit the quality of obstetric management preceding emergency caesarean sections for prolonged labour....

  18. Laryngotracheal Injury following Prolonged Endotracheal Intubation

    Directory of Open Access Journals (Sweden)

    J. Mehdizadeh


    Full Text Available Background: Prolonged endotracheal intubation is a growing method for supporting ventilation in patients who require intensive care. Despite considerable advancement in endotracheal intubation, this method still has some complications; the most important is laryngo-tracheal injuries. Methods: Over a 2-year period, this retrospective study was conducted on 57 patients with history of prolonged intubation who were referred to the ENT Department of Amir Alam Hospital. For each patient, a complete evaluation including history, physical examination, and direct laryngoscopy and bronchoscopy was done under general anesthesia. Results: Fifty-seven patients (44 male; mean age, 23.014.7 years were studied. Mean intubation period was 15.88 days. The most common presenting symptom was dyspnea (62%. Head trauma was responsible for most cases of intubation (72.4%. The most common types of tracheal and laryngeal lesions were tracheal (56.9% and subglottic (55.2% stenosis, respectively. Mean length of tracheal stenosis was 0.810.83 cm. There was a statistically significant relationship between length of tracheal stenosis and intubation period (P=0.0001 but no relation was observed between tracheal stenosis and age, sex, and etiology of intubation (All P=NS. Among the glottic lesions, inter- arytenoids adhesion was the most common lesion (25.9%. No statistically significant relation was found between glottic and subglottic lesions and age, sex and intubation period (all P=NS. Length of stenosis and intubation period was significantly greater in tracheal/ subglottic lesions than those in glottic/ supraglottic lesions (all P=NS. Conclusion: After prolonged endotracheal intubation, laryngo-tracheal lesions had no relation with patient’s age, sex, and cause of intubation.There was direct relation between length of tracheal stenosis and intubation period. Glottic lesions were more commonly observed in head trauma patients. Lesion length and intubation

  19. Prolonged parenteral nutrition after neonatal gastrointestinal surgery

    DEFF Research Database (Denmark)

    Estmann, Anne; Qvist, Niels; Husby, Steffen


    INTRODUCTION: Long-term treatment with parenteral nutrition (PN) may be essential for survival in infants after neonatal gastrointestinal surgery. It seemed well indicated in a population-based study to estimate the need for long-term PN and to characterize the infants that received TPN with regard...... to diagnosis and clinical course. METHODOLOGY: This study reviews the clinical course of infants with gastrointestinal disease (gastroschisis, intestinal atresia, omphalocele, volvulus, Hirschsprung's disease and necrotizing enterocolitis) with a prolonged need for parenteral nutrition in the Western part...

  20. Direct Light-up of cAMP Derivatives in Living Cells by Click Reactions

    Directory of Open Access Journals (Sweden)

    Yan Xu


    Full Text Available 8-Azidoadenosine 3′,5′-cyclic monophosphate (8-azido cAMP was directly detected in living cells, by applying Cu-free azide-alkyne cycloaddition to probe cAMP derivatives by fluorescence light-up. Fluorescence emission was generated by two non-fluorescent molecules, 8-azido cAMP as a model target and difluorinated cyclooctyne (DIFO reagent as a probe. The azide-alkyne cycloaddition reaction between 8-azido cAMP and DIFO induces fluorescence in 8-azido cAMP. The fluorescence emission serves as a way to probe 8-azido cAMP in cells.

  1. Analysis of AmpC β-lactamase Gene in Pseudomonas aeruginosa

    Institute of Scientific and Technical Information of China (English)

    NI Ming; ZHANG Dongshen; QI Junying


    The gene and the amino acid sequence of the structural and regulatory region of the Pseudomonas aeruginosa with different resistance patterns were analyzed. Six strains with different resistance patterns were selected and the AmpC β-lactamase was identified. The objective gene fragment was amplified by colonies PCR. The sequences of the PCR-products were analyzed. The DNA sequence of the structural gene ampC and the regulatory genes ampR, ampD and ampE was detected. The 6 strains and the wild-type Pseudomonas aeruginosa are highly homogeneous in structural and regulatory region. Some new mutant points were found.

  2. Intracellular cAMP signaling by soluble adenylyl cyclase. (United States)

    Tresguerres, Martin; Levin, Lonny R; Buck, Jochen


    Soluble adenylyl cyclase (sAC) is a recently identified source of the ubiquitous second messenger cyclic adenosine 3',5' monophosphate (cAMP). sAC is distinct from the more widely studied source of cAMP, the transmembrane adenylyl cyclases (tmACs); its activity is uniquely regulated by bicarbonate anions, and it is distributed throughout the cytoplasm and in cellular organelles. Due to its unique localization and regulation, sAC has various functions in a variety of physiological systems that are distinct from tmACs. In this review, we detail the known functions of sAC, and we reassess commonly held views of cAMP signaling inside cells.

  3. The CytR repressor antagonizes cyclic AMP-cyclic AMP receptor protein activation of the deoCp2 promoter of Escherichia coli K-12

    DEFF Research Database (Denmark)

    Søgaard-Andersen, Lotte; Martinussen, J; Møllegaard, N E


    We have investigated the regulation of the Escherichia coli deoCp2 promoter by the CytR repressor and the cyclic AMP (cAMP) receptor protein (CRP) complexed to cAMP. Promoter regions controlled by these two proteins characteristically contain tandem cAMP-CRP binding sites. Here we show that (i) Cyt......R selectively regulated cAMP-CRP-dependent initiations, although transcription started from the same site in deoCp2 in the absence or presence of cAMP-CRP; (ii) deletion of the uppermost cAMP-CRP target (CRP-2) resulted in loss of CytR regulation, but had only a minor effect on positive control by the c...... are required for efficient CytR repression of deoCp2. Models for the action of CytR are discussed in light of these findings....

  4. Activation of protein kinase A and exchange protein directly activated by cAMP promotes adipocyte differentiation of human mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    Bingbing Jia

    Full Text Available Human mesenchymal stem cells are primary multipotent cells capable of differentiating into several cell types including adipocytes when cultured under defined in vitro conditions. In the present study we investigated the role of cAMP signaling and its downstream effectors, protein kinase A (PKA and exchange protein directly activated by cAMP (Epac in adipocyte conversion of human mesenchymal stem cells derived from adipose tissue (hMADS. We show that cAMP signaling involving the simultaneous activation of both PKA- and Epac-dependent signaling is critical for this process even in the presence of the strong adipogenic inducers insulin, dexamethasone, and rosiglitazone, thereby clearly distinguishing the hMADS cells from murine preadipocytes cell lines, where rosiglitazone together with dexamethasone and insulin strongly promotes adipocyte differentiation. We further show that prostaglandin I(2 (PGI(2 may fully substitute for the cAMP-elevating agent isobutylmethylxanthine (IBMX. Moreover, selective activation of Epac-dependent signaling promoted adipocyte differentiation when the Rho-associated kinase (ROCK was inhibited. Unlike the case for murine preadipocytes cell lines, long-chain fatty acids, like arachidonic acid, did not promote adipocyte differentiation of hMADS cells in the absence of a PPARγ agonist. However, prolonged treatment with the synthetic PPARδ agonist L165041 promoted adipocyte differentiation of hMADS cells in the presence of IBMX. Taken together our results emphasize the need for cAMP signaling in concert with treatment with a PPARγ or PPARδ agonist to secure efficient adipocyte differentiation of human hMADS mesenchymal stem cells.

  5. Leptin inhibits glycogen catabolism but does not modify acutely the suppressive effect of insulin on glucose production and glycogenolysis stimulated by 8-Br-cAMP in rat liver perfused in situ. (United States)

    Leonardo, Eledir Silveira; Bassoli, Bruna Kempfer; Cassolla, Priscila; Borba-Murad, Glaucia Regina; Bazotte, Roberto Barbosa; De Souza, Helenir Medri


    Leptin, a hormone secreted by the adipocytes, plays a central role in glucose metabolism and the action of insulin. Here we assessed, by means of rat-liver perfusion, the direct influence of physiological (10 ng/ml) and supraphysiological (50 or 100 ng/ml) concentrations of leptin on the suppressive effect of insulin on the glucose production and glycogenolysis stimulated by 8-bromoadenosine-3':5'-monophosphate (8-Br-cAMP). Portal infusion of insulin (20 microU/ml) or leptin (10 ng/ml) reduced (pglycogenolysis induced by 8-Br-cAMP (0.3 microM). However, portal infusion of physiological (10 ng/ml) and supraphysiological (50 or 100 ng/ml) concentrations of leptin together with the insulin did not modify the suppressive effect of the latter on the glucose production and glycogenolysis stimulated by 8-Br-cAMP. Moreover, prolonging the period of leptin infusion from 20 to 40 min also failed to influence the liver response to insulin. Thus, we conclude that: (a) leptin, at physiological levels, has a direct and acute effect, inhibiting the glucose production and glycogenolysis stimulated by 8-Br-cAMP; (b) leptin, at either physiological or supraphysiological concentrations, has no short-term influence on the suppressive effect of insulin on glycogen catabolism stimulated by 8-Br-cAMP.

  6. Predictors of post coronary artery bypass grafting atrial fibrillation

    Institute of Scientific and Technical Information of China (English)

    Tongtong Shen; Qijun Shan; Biao Yuan; Bing Yang; Chun Chen; Dongjie Xu; Minglong Chen; Jiangang Zou; Kejiang Cao


    Objective: To investigate the incidence and relative risk factors of post coronary artery bypass grafting(post-CABG) atrial fibrillation (AF). Methods: 312 patients with CABG were reviewed and divided into an AF group and a non-AF group. Statistical analysis was used to compare the data between the two groups and screen for risk factors of post-CABG AF. Results: 103/312(33.01%) patients developed post-CABG AF. Univariate analysis showed that patients in AF group compared with those in non-AF group were more likely to have advanced age (≥ 70 years), early postoperative withdrawal of β-blockers, hypertension, left atrial enlargement ( ≥40 mm), a history of AF, prolonged p-wave duration ( ≥ 120 ms) and increased number of grafts (≥3). Multivariate logistic regression analysis showed that advanced age (≥70 years), early postoperative withdrawal of β-blockers, hypertension, left atrial enlargement (≥40 mm) and a history of AF were highly related to post-CABG AF. Conclusion: The incidence of AF in patients following CABG was 33.01% in this study. Advanced age, early postoperative withdrawal of β-blockers,hypertension, left atrial enlargement and a history of AF were independent risk factors of post-CABG AF.

  7. Inhibition of AMP deaminase as therapeutic target in cardiovascular pathology. (United States)

    Zabielska, Magdalena A; Borkowski, Tomasz; Slominska, Ewa M; Smolenski, Ryszard T


    AMP deaminase (AMPD; EC catalyzes hydrolysis of the amino group from the adenine ring of AMP resulting in production of inosine 5'-monophosphate (IMP) and ammonia. This reaction helps to maintain healthy cellular energetics by removing excess AMP that accumulates in energy depleted cells. Furthermore, AMPD permits the synthesis of guanine nucleotides from the larger adenylate pool. This enzyme competes with cytosolic 5'-nucleotidases (c5NT) for AMP. Adenosine, a product of c5NT is a vasodilator, antagonizes inotropic effects of catecholamines and exerts anti-platelet, anti-inflammatory and immunosuppressive activities. The ratio of AMPD/c5NT defines the amount of adenosine produced in adenine nucleotide catabolic pathway. Inhibition of AMPD could alter this ratio resulting in increased adenosine production. Besides the potential effect on adenosine production, elevation of AMP due to inhibition of AMPD could also lead to activation of AMP regulated protein kinase (AMPK) with myriad of downstream events including enhanced energetic metabolism, mitochondrial biogenesis and cytoprotection. While the benefits of these processes are well appreciated in cells such as skeletal or cardiac myocytes its role in protection of endothelium could be even more important. Therapeutic use of AMPD inhibition has been limited due to difficulties with obtaining compounds with adequate characteristics. However, endothelium seems to be the easiest target as effective inhibition of AMPD could be achieved at much lower concentration than in the other types of cells. New generation of AMPD inhibitors has recently been established and its testing in context of endothelial and organ protection could provide important basic knowledge and potential therapeutic tools.

  8. [Autologous fat grafting in children]. (United States)

    Baptista, C; Bertrand, B; Philandrianos, C; Degardin, N; Casanova, D


    Lipofilling or fat grafting transfer is defined as a technique of filling soft tissue by autologous fat grafting. The basic principle of lipofilling is based on a harvest of adipose tissue, followed by a reinjection after treatment. Lipofilling main objective is a volume defect filling, but also improving cutaneous trophicity. Lipofilling specificities among children is mainly based on these indications. Complications of autologous fat grafting among children are the same as those in adults: we distinguish short-term complications (intraoperative and perioperative) and the medium and long-term complications. The harvesting of fat tissue is the main limiting factor of the technique, due to low percentage of body fat of children. Indications of lipofilling among children may be specific or similar to those in adults. There are two types of indications: cosmetic, in which the aim of lipofilling is correcting a defect density, acquired (iatrogenic, post-traumatic scar) or malformation (otomandibular dysplasia, craniosynostosis, Parry Romberg syndrom, Poland syndrom, pectus excavatum…). The aim of functional indications is correcting a velar insufficiency or lagophthalmos. In the paediatric sector, lipofilling has become an alternative to the conventional techniques, by its reliability, safety, reproducibility, and good results.

  9. Lifetime Prolonging Algorithms for Underwater Sensor Networks

    Institute of Scientific and Technical Information of China (English)

    GUO Zhong-wen; LI Zhi-wei; YU Lei


    Underwater acoustic modem technology has attained a level of maturity to support underwater acoustic sensor networks (UASNs) which are generally formed by acoustically connected sensor nodes and a surface station providing a link to an on-shore control center. While many applications require long-term monitoring of the deployment area, the battery-powered network nodes limit the lifetime of UASNs. Therefore, designing a UASN that minimizes the power consumption while maximizing lifetime becomes a very difficult task. In this paper, a method is proposed to determine the optimum number of clusters through combining an application-specific protocol architecture and underwater acoustic communication model so as to reduce the energy dissipation of UASNs. Deploying more sensor nodes which work alternately is another way to prolong the lifetime of UASNs. An algorithm is presented for selecting sensor nodes and putting them into operation in each round, ensuring the monitoring to the whole given area. The present results show that the algorithm can help prolong system lifetime remarkably when it is applied to other conventional approaches for sensor networks under the condition that the sensor node density is high.

  10. Hybrid Graft Anterior Cruciate Ligament Reconstruction: A Predictable Graft for Knee Stabilization. (United States)

    Alvarez-Pinzon, Andres M; Barksdale, Leticia; Krill, Michael K; Leo, Brian M


    Trauma to the anterior cruciate ligament (ACL) is a season-ending injury and involves months of activity modification and rehabilitation. The annual incidence of ACL tears in the United States is approximately 200,000, which allows for a broad range of individualized treatment options. Various surgical techniques, including transtibial and independent tunnel drilling, allograft and autograft tissue, and various implants, have been described in the literature. This article describes the indications and technique for a hybrid soft tissue graft for ACL reconstruction. Autologous grafts eliminate the risk of disease transmission and have recently been shown to have a lower rerupture rate, particularly in younger, active patients; however, the harvesting of autologous hamstring grafts carries a risk of donor-site morbidity, iatrogenic injury of the graft, and inadequate graft size. In contrast to a traditional autologous soft tissue graft, the hybrid graft allows for graft size customization for a desired reconstruction, especially in cases where autograft hamstrings may be iatrogenically damaged or of inadequate size when harvested. The goal of a hybrid graft ACL reconstruction is to provide a favorable-sized graft with clinical outcomes comparable with autologous soft tissue grafts. In contrast to a traditional autologous soft tissue graft, this technique provides another option in the event of unforeseen deficiencies or complications associated with harvesting and preparation of the autologous gracilis and semitendinosis soft tissue graft.

  11. Prolonged in vivo circulation time by zwitterionic modification of magnetite nanoparticles for blood pool contrast agents. (United States)

    Xiao, Wangchuan; Lin, Jiang; Li, Mingli; Ma, Yongjie; Chen, Yuxin; Zhang, Chunfu; Li, Dan; Gu, Hongchen


    Long circulation time is critical for blood pool contrast agents used in high-resolution magnetic resonance angiography. For iron oxide particle contrast agents, size and surface properties significantly influence their in vivo performance. We developed a novel long-circulating blood pool contrast agent by introducing zwitterionic structure onto the particle surface. Zwitterionic structure was fabricated by 3-(diethylamino)propylamine (DEAPA) grafted onto the surface of ployacrylic acid coated magnetite nanoparticles via EDC/NHS [N-(3-dimethylaminopropyl)-N'-ethylcarbo-diimide hydrochloride/N-hydroxysuccinimide] coupling chemistry. Zwitterionic particles demonstrated five times lower macrophage cell uptake than the original particles and low cell toxicity. Magnetic resonance angiography indicated that zwitterionic nanoparticles had much longer in vivo circulation time than the original particles and were an ideal candidate for blood pool contrast agent. We suppose that zwitterionic modification by DEAPA and EDC/NHS can be used generally for coating nanoparticles with carboxyl surface and to prolong their circulating time.

  12. Wear resistance of the biocompatible phospholipid polymer-grafted highly cross-linked polyethylene liner against larger femoral head. (United States)

    Moro, Toru; Takatori, Yoshio; Kyomoto, Masayuki; Ishihara, Kazuhiko; Kawaguchi, Hiroshi; Hashimoto, Masami; Tanaka, Takeyuki; Oshima, Hirofumi; Tanaka, Sakae


    The use of larger femoral heads to prevent the dislocation of artificial hip joints has recently become more common. However, concerns about the subsequent use of thinner polyethylene liners and their effects on wear rate have arisen. Previously, we prepared and evaluated the biological and mechanical effects of a novel highly cross-linked polyethylene (CLPE) liner with a nanometer-scaled graft layer of poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC). Our findings showed that the PMPC-grafted particles were biologically inert and caused no subsequent bone resorptive responses and that the PMPC-grafting markedly decreased wear in a hip joint simulator. However, the metal or ceramic femoral heads used in this previous study had a diameter of 26 mm. Here, we investigated the wear-resistance of the PMPC-grafted CLPE liner with a 40-mm femoral head during 10 × 10(6) cycles of loading in the hip joint simulator. The results provide preliminary evidence that the grafting markedly decreased gravimetric wear rate and the volume of wear particles, even when coupled with larger femoral heads. Thus, we believe the PMPC-grafting will prolong artificial hip joint longevity both by preventing aseptic loosening and by improving the stability of articular surface.

  13. "cAMP sponge": a buffer for cyclic adenosine 3', 5'-monophosphate.

    Directory of Open Access Journals (Sweden)

    Konstantinos Lefkimmiatis

    Full Text Available BACKGROUND: While intracellular buffers are widely used to study calcium signaling, no such tool exists for the other major second messenger, cyclic AMP (cAMP. METHODS/PRINCIPAL FINDINGS: Here we describe a genetically encoded buffer for cAMP based on the high-affinity cAMP-binding carboxy-terminus of the regulatory subunit RIbeta of protein kinase A (PKA. Addition of targeting sequences permitted localization of this fragment to the extra-nuclear compartment, while tagging with mCherry allowed quantification of its expression at the single cell level. This construct (named "cAMP sponge" was shown to selectively bind cAMP in vitro. Its expression significantly suppressed agonist-induced cAMP signals and the downstream activation of PKA within the cytosol as measured by FRET-based sensors in single living cells. Point mutations in the cAMP-binding domains of the construct rendered the chimera unable to bind cAMP in vitro or in situ. Cyclic AMP sponge was fruitfully applied to examine feedback regulation of gap junction-mediated transfer of cAMP in epithelial cell couplets. CONCLUSIONS: This newest member of the cAMP toolbox has the potential to reveal unique biological functions of cAMP, including insight into the functional significance of compartmentalized signaling events.

  14. Twist and its effect on ACL graft forces

    NARCIS (Netherlands)

    Arnold, MP; Blankevoort, L; ten Ham, A; Verdonschot, N; van Kampen, A


    Graft tension is a controversial topic in anterior cruciate ligament (ACL) surgery. Evidence suggests a narrow range of graft tensions, which allow the graft to remodel to a stable and mature neoligament. In previous cadaver experiments, we showed that twisting the graft could modulate the graft for

  15. Twist and its effect on ACL graft forces.

    NARCIS (Netherlands)

    Arnold, M.P.; Blankevoort, L.; Ham, A. ten; Verdonschot, N.J.J.; Kampen, A. van


    Graft tension is a controversial topic in anterior cruciate ligament (ACL) surgery. Evidence suggests a narrow range of graft tensions, which allow the graft to remodel to a stable and mature neoligament. In previous cadaver experiments, we showed that twisting the graft could modulate the graft for

  16. Fixation of tibial plateau fractures with synthetic bone graft versus natural bone graft: a comparison study.

    LENUS (Irish Health Repository)

    Ong, J C Y


    The goal of this study was to determine differences in fracture stability and functional outcome between synthetic bone graft and natural bone graft with internal fixation of tibia plateau metaphyseal defects.


    Institute of Scientific and Technical Information of China (English)

    S. Termnak; K. Sintasanai; T. Amomsakchai; T. Nipithakul; D. Triampo


    The scanning force microscopy (SFM)/chemical force microscopy (CFM) were used to study the growth of grafted polyacrylamide (PAM) chains onto polyethylene (PE)-film with varying grafting time. Results from the CFM reveal reduced interaction between the probe and areas with grafted-PAM on the surface. The topography and the friction trace-minus-retrace (TMR) images are complementary to one another resulting from the reduced interaction of the probe that has specificity to chemical domains.

  18. Outcomes of AV Fistulas and AV Grafts after Interventional Stent-Graft Deployment in Haemodialysis Patients

    Energy Technology Data Exchange (ETDEWEB)

    Schmelter, Christopher, E-mail:; Raab, Udo, E-mail: [Klinikum Ingolstadt, Department of Diagnostic and Interventional Radiology (Germany); Lazarus, Friedrich, E-mail: [Klinikum Ingolstadt, Department of Nephrology (Germany); Ruppert, Volker, E-mail: [Klinikum Ingolstadt, Department of Vascular Surgery (Germany); Vorwerk, Dierk, E-mail: [Klinikum Ingolstadt, Department of Diagnostic and Interventional Radiology (Germany)


    PurposeThe study was designed to assess outcomes of arteriovenous (AV) accesses after interventional stent-graft deployment in haemodialysis patients.Materials and Methods63 haemodialysis patients with 66 AV fistulas and AV grafts were treated by interventional stent-graft deployment from 2006 to 2012 at our hospital. Data of these patients were retrospectively analysed for location of deployed stent-grafts, occurrence and location of (re-)stenosis and (re-)thrombosis. Complex stenosis was the most frequent indication for stent-graft deployment (45.5 %), followed by complications of angioplasty with vessel rupture or dissection (31.8 %).ResultsA high rate of procedural success was achieved (98.5 %). The most frequent location of the deployed stent-graft was the draining vein (66.7 %). Stent-graft deployment was more frequent in AV grafts than in AV fistulas. Primary patency was 45.5 % at 6 month, 31.3 % at 12 month and 19.2 % at 24 month. Primary patency was significantly better for AV fistulas than for AV grafts with deployed stent-grafts. Patency of the deployed stent-graft was much better than overall AV access primary patency with deployed stent-graft. Re-stenosis with thrombosis was the most frequent indication for re-intervention. Most frequent location of re-stenosis was the draining vein (37.1 %), followed by stenosis at the AV access (29.5 %) and the deployed stent-graft (23.5 %).ConclusionRe-stenosis and re-thrombosis remain frequent in AV fistulas and AV grafts in haemodialysis patients despite stent-graft deployment. Re-stenosis of the deployed stent-graft is, only in the minority of the cases, responsible for AV access dysfunction.

  19. A novel, blocking, Fc-silent anti-CD40 monoclonal antibody prolongs nonhuman primate renal allograft survival in the absence of B cell depletion. (United States)

    Cordoba, F; Wieczorek, G; Audet, M; Roth, L; Schneider, M A; Kunkler, A; Stuber, N; Erard, M; Ceci, M; Baumgartner, R; Apolloni, R; Cattini, A; Robert, G; Ristig, D; Munz, J; Haeberli, L; Grau, R; Sickert, D; Heusser, C; Espie, P; Bruns, C; Patel, D; Rush, J S


    CD40-CD154 pathway blockade prolongs renal allograft survival in nonhuman primates (NHPs). However, antibodies targeting CD154 were associated with an increased incidence of thromboembolic complications. Antibodies targeting CD40 prolong renal allograft survival in NHPs without thromboembolic events but with accompanying B cell depletion, raising the question of the relative contribution of B cell depletion to the efficacy of anti-CD40 blockade. Here, we investigated whether fully silencing Fc effector functions of an anti-CD40 antibody can still promote graft survival. The parent anti-CD40 monoclonal antibody HCD122 prolonged allograft survival in MHC-mismatched cynomolgus monkey renal allograft transplantation (52, 22, and 24 days) with accompanying B cell depletion. Fc-silencing yielded CFZ533, an antibody incapable of B cell depletion but still able to potently inhibit CD40 pathway activation. CFZ533 prolonged allograft survival and function up to a defined protocol endpoint of 98-100 days (100, 100, 100, 98, and 76 days) in the absence of B cell depletion and preservation of good histological graft morphology. CFZ533 was well-tolerated, with no evidence of thromboembolic events or CD40 pathway activation and suppressed a gene signature associated with acute rejection. Thus, use of the Fc-silent anti-CD40 antibody CFZ533 appears to be an attractive approach for preventing solid organ transplant rejection.

  20. Postaggregative Differentiation Induction by Cyclic AMP in Dictyostelium : Intracellular Transduction Pathway and Requirement for Additional Stimuli

    NARCIS (Netherlands)

    Schaap, Pauline; Lookeren Campagne, Michiel M. van; Driel, Roel van; Spek, Wouter; Haastert, Peter J.M. van; Pinas, Johan


    Cyclic AMP induces postaggregative differentiation in aggregation competent cells of Dictyostelium by interacting with cell surface cAMP receptors. We investigated the transduction pathway of this response and additional requirements for the induction of postaggregative differentiation. Optimal indu

  1. Regulatory T cell expressed MyD88 is critical for prolongation of allograft survival. (United States)

    Borges, Christopher M; Reichenbach, Dawn K; Kim, Beom Seok; Misra, Aditya; Blazar, Bruce R; Turka, Laurence A


    MyD88 signaling directly promotes T-cell survival and is required for optimal T-cell responses to pathogens. To examine the role of T-cell-intrinsic MyD88 signals in transplantation, we studied mice with targeted T-cell-specific MyD88 deletion. Contrary to expectations, we found that these mice were relatively resistant to prolongation of graft survival with anti-CD154 plus rapamycin in a class II-mismatched system. To specifically examine the role of MyD88 in Tregs, we created a Treg-specific MyD88-deficient mouse. Transplant studies in these animals replicated the findings observed with a global T-cell MyD88 knockout. Surprisingly, given the role of MyD88 in conventional T-cell survival, we found no defect in the survival of MyD88-deficient Tregs in vitro or in the transplant recipients and also observed intact cell homing and expression of Treg effector molecules. MyD88-deficient Tregs also fail to protect allogeneic bone marrow transplant recipients from chronic graft-versus-host disease, confirming the observations of defective regulation seen in a solid organ transplant system. Together, our data define MyD88 as having a divergent requirement for cell survival in non-Tregs and Tregs, and a yet-to-be defined survival-independent requirement for Treg function during the response to alloantigen.

  2. The autologus graft of epithelial tissue culture

    Directory of Open Access Journals (Sweden)

    Minaee B


    Full Text Available With the intention of research about culture and autologus graft of epithelial tissue we used 4 french Albino Rabbits with an average age of 2 months. After reproduction on the support in EMEM (Eagle's Minimum Essential Medium we used this for graft after 4 weeks. This region which grafted total replaced. After fixation of this sample and passing them through various process, histological sections were prepared. These sections were stained with H & E and masson's trichrome and studied by light microscope. We succeeded in graft. We hope in the near future by using the method of epithelium tissue culture improving to treat burned patients.

  3. Role of tacrolimus prolonged release in the prevention of allograft rejection

    Directory of Open Access Journals (Sweden)

    Peter Abrams


    Full Text Available Peter Abrams, Abhinav Humar, Henkie P TanDepartment of Surgery, Thomas E Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pennsylvania, USAAbstract: Successful management of the solid-organ transplant recipient begins with prevention of rejection and achieving a balance between insufficient and excessive immunosuppression. Standard tacrolimus therapy for prevention of solid-organ transplant rejection consists of 2 divided doses per day. In an effort to simplify tacrolimus dosing to once daily, a new formulation (tacrolimus prolonged release [PR] was chosen for its combination of a similar extent of bioavailability and a substantially reduced rate of clearance. Several clinical conversion studies have now been completed using PR to clarify its pharmacokinetics, efficacy at prevention of allograft rejection, and safety profiles in solid-organ transplant patients. A cohort of 67 stable kidney transplant recipients was converted from standard tacrolimus to PR in an open-label, multicenter study in the United States and Canada. A second open-label, multicenter study was performed in liver transplant recipients with stable graft function on standard tacrolimus therapy converted to PR. A third conversion study was performed as an open-label study at 5 centers in the United States in stable pediatric liver transplant recipients. As medication noncompliance can significantly contribute to the incidence of graft rejection and graft loss in transplant recipients, a potentially significant advance in the transplant community’s ongoing mission to optimize prevention of rejection occurred with the development of a once-daily tacrolimus PR. The results of these preliminary studies suggest that select solid-organ transplant recipients converted to PR can be safely maintained using the same monitoring and patient care techniques historically used for standard tacrolimus therapy.Keywords: immunosuppression, tacrolimus allograft

  4. Neurohumoral responses during prolonged exercise in humans

    DEFF Research Database (Denmark)

    Nybo, Lars; Nielsen, Bodil; Blomstrand, Eva


    in the hyperthermic trial, with a concomitant increase in perceived exertion (P brain had a small release of tryptophan (arteriovenous difference of -1.2 +/- 0.3 micromol/l), whereas a net balance was obtained during the two exercise trials. Both the arterial and jugular venous dopamine levels...... became elevated during the hyperthermic trial, but the net release from the brain was unchanged. During exercise, the O2/CHO was similar across trials, but, during recovery from the hyperthermic trial, the ratio decreased to 3.8 +/- 0.3 (P ...This study examined neurohumoral alterations during prolonged exercise with and without hyperthermia. The cerebral oxygen-to-carbohydrate uptake ratio (O2/CHO = arteriovenous oxygen difference divided by arteriovenous glucose difference plus one-half lactate), the cerebral balances of dopamine...

  5. Multifactorial QT Interval Prolongation and Takotsubo Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Michael Gysel


    Full Text Available A 71-year-old woman collapsed while working as a grocery store cashier. CPR was performed and an AED revealed torsades de pointes (TdP. She was subsequently defibrillated resulting in restoration of sinus rhythm with a QTc interval of 544 msec. Further evaluation revealed a diagnosis of Takotsubo Cardiomyopathy (TCM contributing to the development of a multifactorial acquired long QT syndrome (LQTS. The case highlights the role of TCM as a cause of LQTS in the setting of multiple risk factors including old age, female gender, hypokalemia, and treatment with QT prolonging medications. It also highlights the multifactorial nature of acquired LQTS and lends support to growing evidence of an association with TCM.

  6. Elevated cAMP increases aquaporin-3 plasma membrane diffusion

    DEFF Research Database (Denmark)

    Marlar, Saw; Christensen, Eva Arnspang; Koffman, Jennifer Skaarup


    .05)]. Immunoelectron microscopy showed no obvious difference in AQP3-EGFP expression levels or localization in the plasma membrane upon forskolin stimulation. Thus AQP3-EGFP diffusion is altered upon increased cAMP, which may correspond to basolateral adaptations in response to the increased apical water readsorption...

  7. Modeling of CO2 absorber using an AMP solution

    DEFF Research Database (Denmark)

    Gabrielsen, Jostein; Michelsen, Michael Locht; Stenby, Erling Halfdan


    Abstract: An explicit model for carbon dioxide (CO2) solubility in an aqueous solution of 2-amino-2-methyl-1-propanol (AMP) has been proposed and an expression for the heat of absorption of CO2 has been developed as a function of loading and temperature. A rate-based steady-state model for CO2 ab...

  8. Pico amp measurement circuit with high system isolation

    Energy Technology Data Exchange (ETDEWEB)

    Akins, J.H.


    An increase in sensitivity of 2000 can be achieved by modifying a Tektronics P6042 Hall Effect probe to accept 2000 turns as opposed to the standard single turn current input line. This increase in sensitivity coupled with a special self-zeroing amplifier allows the measurement of Pico-amps while maintaining high system isolation.

  9. Simulation of Organic Solar Cells Using AMPS-1D Program

    Directory of Open Access Journals (Sweden)

    Samah G. Babiker


    Full Text Available The analysis of microelectronic and photonic structure in one dimension program [AMPS-1D] program has been successfully used to study inorganic solar cells. In this work the program has been used to optimize the performance of the organic solar cells. The cells considered consist of poly(2-methoxy-5-(3,7- dimethyloctyloxy-1,4-phenylenevinylene [MDMO-PPV

  10. 7 CFR 772.10 - Transfer and assumption-AMP loans. (United States)


    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Transfer and assumption-AMP loans. 772.10 Section 772..., DEPARTMENT OF AGRICULTURE SPECIAL PROGRAMS SERVICING MINOR PROGRAM LOANS § 772.10 Transfer and assumption—AMP loans. (a) Eligibility. The Agency may approve transfers and assumptions of AMP loans when: (1)...

  11. 染色体介导的AmpC酶研究进展

    Institute of Scientific and Technical Information of China (English)

    刘晶; 多丽波


    AmpC β-内酰胺酶(AmpC)存在于大多数革兰阴性杆菌中,主要由染色体介导,在缺乏β-内酰胺类抗生素时,只产生少量的β-内酰胺酶,但在β-内酰胺类抗生素诱导剂存在时,AmpC酶的产量明显增加,导致对第三代头孢菌素耐药,目前认为AmpC酶的诱导调节机理与ampR、ampG、ampD有关;而大肠埃希菌缺乏调节基因ampR,AmpC酶不被诱导,但可以通过ampC启动子和衰减子突变导致高产AmpC酶.此外,质粒介导AmpC酶是近年来出现的新的耐药机制,同样可导致细菌广泛性耐药.

  12. Activation of FoxO transcription factors contributes to the antiproliferative effect of cAMP

    NARCIS (Netherlands)

    Kuiperij, H.B.; Horst, Armando van der; Raaijmakers, Judith; Weijzen, S.; Medema, R.H.; Bos, J.L.; Burgering, B.M.T.; Zwartkruis, G.J.T.


    cAMP is a potent inhibitor of cell proliferation in a variety of cell lines. Downregulation of cyclin D1 and upregulation of the cell cycle inhibitor p27Kip1 are two mechanisms by which cAMP may induce a G1-arrest. Here we show that cAMP inhibits proliferation of cells that constitutively express cy

  13. The modulation of cell surface cAMP receptors from Dictyostelium disscoideum by ammonium sulfate

    NARCIS (Netherlands)

    Haastert, Peter J.M. van


    Dictyostelium discoideum cells contain a heterogeneous population of cell surface cAMP receptors with components possessing different affinities (Kd between 15 and 450 nM) and different off-rates of the cAMP-receptor complex (t½ between 0.7 and 150 s). The association of cAMP to the receptor and the

  14. Nanotribological study of grafted polymer (United States)

    Bouhacina, T.; Aimé, J. P.; Attias, A. J.


    The frictional forces between grafted layers, organosilanes and polymer, on silica and a nanotip have been investigated as a function of the tip velocity. From the interpretation of these results and one gets a step forward for more quantitative information. Les forces de friction entre des couches greffées sur silice et une nanopointe ont été étudiées en fonction de la vitesse de la pointe. À partir de l'interprétation de ces résultats on s'avance vers plus d'infor mations quantitatives.

  15. Paclitaxel modulates TGFbeta signaling in scleroderma skin grafts in immunodeficient mice.

    Directory of Open Access Journals (Sweden)


    Full Text Available BACKGROUND: Systemic sclerosis (SSc is characterized by excessive fibrosis and obliterative vascular lesions. Abnormal TGFbeta activation is implicated in the pathogenesis of SSc. Aberrant TGFbeta/Smad signaling can be controlled by stabilization of microtubules with paclitaxel. METHODS AND FINDINGS: SSc and healthy human skin biopsies were incubated in the presence or absence of paclitaxel followed by transplantation into severe combined immunodeficient mice. TGFbeta signaling, fibrosis, and neovessel formation were evaluated by quantitative RT-PCR and immunohistochemical staining. Paclitaxel markedly suppressed Smad2 and Smad3 phosphorylation and collagen deposition in SSc grafts. As a result, the autonomous maintenance/reconstitution of the SSc phenotype was prevented. Remarkably, SSc grafts showed a 2-fold increase in neovessel formation relative to normal grafts, regardless of paclitaxel treatment. Angiogenesis in SSc grafts was associated with a substantial increase in mouse PECAM-1 expression, indicating the mouse origin of the neovascular cells. CONCLUSION: Low-dose paclitaxel can significantly suppress TGFbeta/Smad activity and lessen fibrosis in SCID mice. Transplantation of SSc skin into SCID mice elicits a strong angiogenesis-an effect not affected by paclitaxel. Although prolonged chemotherapy with paclitaxel at higher doses is associated with pro-fibrotic and anti-angiogenic changes, the findings described here indicate that low-dose paclitaxel may have therapeutic benefits for SSc via modulating TGFbeta signaling.

  16. Design and development of multilayer vascular graft (United States)

    Madhavan, Krishna


    Vascular graft is a widely-used medical device for the treatment of vascular diseases such as atherosclerosis and aneurysm as well as for the use of vascular access and pediatric shunt, which are major causes of mortality and morbidity in this world. Dysfunction of vascular grafts often occurs, particularly for grafts with diameter less than 6mm, and is associated with the design of graft materials. Mechanical strength, compliance, permeability, endothelialization and availability are issues of most concern for vascular graft materials. To address these issues, we have designed a biodegradable, compliant graft made of hybrid multilayer by combining an intimal equivalent, electrospun heparin-impregnated poly-epsilon-caprolactone nanofibers, with a medial equivalent, a crosslinked collagen-chitosan-based gel scaffold. The intimal equivalent is designed to build mechanical strength and stability suitable for in vivo grafting and to prevent thrombosis. The medial equivalent is designed to serve as a scaffold for the activity of the smooth muscle cells important for vascular healing and regeneration. Our results have shown that genipin is a biocompatible crosslinker to enhance the mechanical properties of collagen-chitosan based scaffolds, and the degradation time and the activity of smooth muscle cells in the scaffold can be modulated by the crosslinking degree. For vascular grafting and regeneration in vivo, an important design parameter of the hybrid multilayer is the interface adhesion between the intimal and medial equivalents. With diametrically opposite affinities to water, delamination of the two layers occurs. Physical or chemical modification techniques were thus used to enhance the adhesion. Microscopic examination and graft-relevant functional characterizations have been performed to evaluate these techniques. Results from characterization of microstructure and functional properties, including burst strength, compliance, water permeability and suture

  17. Radiation resistivity of polyacenaphthylene-grafted polyethylene (United States)

    Hayakawa, Kiyoshi; Kawase, Kaoru; Yamakita, Hiromi

    Thin poly (ethylene-g-acenaphthylene) films prepared by the vapor-phase grafting method were subjected to the γ-irradiation in air, and various changes in tensile and structural properties of the film were investigated by comparing with those of the untreated or crosslinked polyethylene film. Polyethylene got to lose its inherent necking property by oxidative degradation and to be brittle-fractured by the irradiation dose less than 100 Mrad in air. The polyacenaphthylene-grafted polyethylenes (extent of grafting, ˜ 54 by {100( P-P°) }/{P°}), however, kept their ductility up to 200 Mrad or more, and the rate of increase in elastic modulus as well as yield strength with the increasing irradiation dose was considerably lower than that of untreated or crosslinked polyethylene. The effect of the grafting extent, and that of the irradiation dose-rate on the fracture energy were also examined. The weight increase of polyethylene due to the oxygen consumption and the resulting formation of carbonyl group which proceeded proportionally with the irradiation dose were remarkably suppressed by the grafting, whereas the double bond formation seemed to be unaffected by it. The grafted film held the original content of gel fraction unchanged during the irradiation in air, but the average molecular weight of the sol fraction decreased gradually. Meanwhile, the gel fraction of the crosslinked polyethylene was degenerated by a small dose of irradiation. The analysis of gaseous products revealed the formation of water, methanol, acetaldehyde and so forth from the irradiated grafted film. The grafting procedure and the subsequent irradiation of the grafted film did not affect the degree of crystallinity of the backbone polyethylene. The role played by the grafted polyacenaphthylene for endowing the radiation resistivity to polyethylene and its inherent limitation in effect were discussed from the structural point of view of the grafted film.

  18. Rapamycin Prolongs Cardiac Allograft Survival in a Mouse Model by Inducing Myeloid-Derived Suppressor Cells. (United States)

    Nakamura, T; Nakao, T; Yoshimura, N; Ashihara, E


    Mammalian target of rapamycin (mTOR) inhibitors are the main immunosuppressive drugs for organ transplant recipients. Nevertheless, the mechanisms by which mTOR inhibitors induce immunosuppression is not fully understood. Myeloid-derived suppressor cells (MDSCs) maintain host immunity; however, the relationship between mTOR inhibitors and MDSCs is unclear. Here, the results from a murine cardiac transplantation model revealed that rapamycin treatment (3 mg/kg, intraperitoneally on postoperative days 0, 2, 4, and 6) led to the recruitment of MDSCs and increased their expression of inducible nitric oxide synthase (iNOS). Immunohistochemical analysis revealed that rapamycin induced the migration of iNOS-expressing MDSCs into the subintimal space within the allograft vessels, resulting in a significant prolongation of graft survival compared with that in the untreated group (67 days vs. 7 days, respectively). These effects were counterbalanced by the administration of an anti-Gr-1, which reduced allograft survival to 21 days. Moreover, adoptive transcoronary arterial transfer of MDSCs from rapamycin-treated recipients prolonged allograft survival; this increase was reversed by the anti-Gr-1 antibody. Finally, co-administration of rapamycin and a mitogen-activated protein kinase kinase (MEK) inhibitor trametinib reversed rapamycin-mediated MDSC recruitment. Thus, the mTOR and Raf/MEK/extracellular signal regulated kinase (ERK) signaling pathways appear to play an important role in MDSC expansion.

  19. Biodegradability of poly(3-hydroxybutyrate) film grafted with vinyl acetate: Effect of grafting and saponification

    Energy Technology Data Exchange (ETDEWEB)

    Wada, Yuki [Department of Biological and Chemical Engineering, Faculty of Engineering, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515 (Japan)]. E-mail:; Seko, Noriaki [Environment and Industrial Materials Research Division, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki-machi, Takasaki, Gunma 370-1292 (Japan); Nagasawa, Naotsugu [Environment and Industrial Materials Research Division, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki-machi, Takasaki, Gunma 370-1292 (Japan); Tamada, Masao [Environment and Industrial Materials Research Division, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki-machi, Takasaki, Gunma 370-1292 (Japan); Kasuya, Ken-ichi [Department of Biological and Chemical Engineering, Faculty of Engineering, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515 (Japan); Mitomo, Hiroshi [Department of Biological and Chemical Engineering, Faculty of Engineering, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515 (Japan)


    Radiation-induced graft polymerization of vinyl acetate (VAc) onto poly(3-hydroxybutyrate) (PHB) film was carried out. At a degree of grafting higher than 5%, the grafted films (PHB-g-VAc) completely lost the enzymatic degradability that is characteristic of PHB due to the grafted VAc covering the surface of the PHB film. However, the biodegradability of the PHB-g-VAc films was recovered when the films were saponified in alkali solution under optimum conditions. Graft chains of the PHB-g-VAc film reacted selectively to become biodegradable polyvinyl alcohol (PVA). The biodegradability of the saponified PHB-g-VAc film increased rapidly with time.

  20. Biodegradability of poly(3-hydroxybutyrate) film grafted with vinyl acetate: Effect of grafting and saponification (United States)

    Wada, Yuki; Seko, Noriaki; Nagasawa, Naotsugu; Tamada, Masao; Kasuya, Ken-ichi; Mitomo, Hiroshi


    Radiation-induced graft polymerization of vinyl acetate (VAc) onto poly(3-hydroxybutyrate) (PHB) film was carried out. At a degree of grafting higher than 5%, the grafted films (PHB-g-VAc) completely lost the enzymatic degradability that is characteristic of PHB due to the grafted VAc covering the surface of the PHB film. However, the biodegradability of the PHB-g-VAc films was recovered when the films were saponified in alkali solution under optimum conditions. Graft chains of the PHB-g-VAc film reacted selectively to become biodegradable polyvinyl alcohol (PVA). The biodegradability of the saponified PHB-g-VAc film increased rapidly with time.

  1. Influence of ischemia before vein grafting on early hyperplasia of the graft and the dynamic changes of the intima after grafting

    Directory of Open Access Journals (Sweden)

    Zou RongJiang


    Full Text Available Abstract Background To investigate both the influence of ischemia before grafting on early hyperplasia of the vein grafts, and the dynamic changes of the intima after grafting in a rabbit model of vein graft disease. Methods We performed paired vein graft experiments under different ischemic conditions (15 vs. 60 min; 15 vs. 90 min in the neck of the rabbits and compared the differences between the grafts. Clopidogrel, an anti-platelet agent, was administered before and after surgery. Twenty-eight days after the grafting procedure, the veins were evaluated microscopically. The dynamic changes of the intima after grafting were evaluated by scanning electron microscopy over time. Results The vein grafts subjected to 60- or 90-min ischemia exhibited no differences compared to those subjected to 15-min ischemia in terms of the mean thickness of the intimal, medial, and adventitial layers of the graft. Similarly, there was no difference in the Ki-67 labeling index (proliferation marker between the vein grafts. Vein grafts with 15-min ischemia lost endothelial cells (ECs but healed by 3 days post graft, whereas vein grafts with 90-min ischemia suffered serious EC loss, which was restored with new ECs during days 2 to 14 post graft. Conclusions Ninety-minute ischemia before vein grafting can cause serious EC loss, but does not increase early intimal hyperplasia when clopidogrel is administered. Protecting the vein from ischemia and reperfusion injury preserves ECs.

  2. 耐药不动杆菌AmpC酶及其相关基因分析%AmpC β-lactamase gene in Acinetobacter and its gene analysis

    Institute of Scientific and Technical Information of China (English)

    杨雪静; 李向阳


    目的 了解不动杆菌产AmpC酶的情况,研究AmpC酶的调控基因AmpD、AmpR对产酶的影响.方法 126株不动杆菌,用Nitrocefin显色法、头孢西丁纸片筛选法和三维试验进行AmpC酶的检测,AmpC基因引物对提取的质粒DNA和染色体DNA进行PCR扩增并测序,对AmpC基因扩增阳性菌株进行AmpR、AmpD基因的扩增.结果 本组不动杆菌总β-内酰胺酶的检出率为78.6%(99/126).AmpC基因引物对质粒DNA和染色体DNA进行PCR扩增并测序显示,染色体DNA中存在AmpC基因,质粒DNA中未检测出AmpC基因.三维试验与PCR法相比,假阳性率为54.7%,假阴性率为17.4%.结论 不动杆菌产AmpC酶率较高,AmpC基因位于染色体上,在质粒上未发现.不动杆菌中AmpD、AmpR基因的改变导致AmpC酶表达水平的变化.AmpD的改变比AmpR改变更多见.三维试验与PCR法扩增AmpC基因检测方法相比,有一定的假阳性.除了亚胺培南外,产AmpC酶菌株的耐药率较不产AmpC酶株为高.

  3. Selective down-regulation of cell surface cAMP-binding sites and cAMP-induced responses in Dictyostelium discoideum

    NARCIS (Netherlands)

    Kesbeke, Fanja; Haastert, Peter J.M. van


    Extracellular cAMP induces an intracellular accumulation of cAMP and cGMP levels in Dictyostelium discoideum, cAMP is detected by cell-surface receptors which are composed of a class of fast-dissociating sites (t1/2 = 1-2 s) and a class of slow-dissociating sites (t1/2 = 15-150 s). Exposure of D. di

  4. Biological roles of cAMP: variations on a theme in the different kingdoms of life. (United States)

    Gancedo, Juana M


    Cyclic AMP (cAMP) plays a key regulatory role in most types of cells; however, the pathways controlled by cAMP may present important differences between organisms and between tissues within a specific organism. Changes in cAMP levels are caused by multiple triggers, most affecting adenylyl cyclases, the enzymes that synthesize cAMP. Adenylyl cyclases form a large and diverse family including soluble forms and others with one or more transmembrane domains. Regulatory mechanisms for the soluble adenylyl cyclases involve either interaction with diverse proteins, as happens in Escherichia coli or yeasts, or with calcium or bicarbonate ions, as occurs in mammalian cells. The transmembrane cyclases can be regulated by a variety of proteins, among which the α subunit and the βγ complex from G proteins coupled to membrane receptors are prominent. cAMP levels also are controlled by the activity of phosphodiesterases, enzymes that hydrolyze cAMP. Phosphodiesterases can be regulated by cAMP, cGMP or calcium-calmodulin or by phosphorylation by different protein kinases. Regulation through cAMP depends on its binding to diverse proteins, its proximal targets, this in turn causing changes in a variety of distal targets. Specifically, binding of cAMP to regulatory subunits of cAMP-dependent protein kinases (PKAs) affects the activity of substrates of PKA, binding to exchange proteins directly activated by cAMP (Epac) regulates small GTPases, binding to transcription factors such as the cAMP receptor protein (CRP) or the virulence factor regulator (Vfr) modifies the rate of transcription of certain genes, while cAMP binding to ion channels modulates their activity directly. Further studies on cAMP signalling will have important implications, not only for advancing fundamental knowledge but also for identifying targets for the development of new therapeutic agents.

  5. Ethylene vinyl acetate based radiation grafted hydrophilic matrices: Process parameter standardization, grafting kinetics and characterization (United States)

    Chaudhari, C. V.; Mondal, R. K.; Dubey, K. A.; Grover, V.; Panicker, L.; Bhardwaj, Y. K.; Varshney, L.


    A transparent, elastomeric, grafted matrix for several potential applications was synthesized by single-step simultaneous radiation grafting of methacrylic acid onto ethylene vinyl acetate (EVA). CuSO4 was found to be the most suitable homo-polymerization inhibitor among different inhibitors tried. The grafting kinetics was found to be a strong function of dose rate (D) and monomer content (M) and an equation relating grafting rate Rg=Kg [M]1.13D0.23 was deduced. Crystallinity of the grafted matrices as assessed from XRD and DSC measurements indicated decrease in crystalline content with increase in grafting yield, suggesting crystalline domain of EVA get disrupted on grafting. Elastic modulus increased linearly with the increase in grafting yield, though elongation at break decreased precipitously from 900% to 30% at even ~9% grafting. Thermo-gravimetric analysis showed three step weight loss of the grafted EVA matrix. The grafting of MAA resulted in increase in surface energy mainly due to enhanced polar component.

  6. A novel initiating system for wool grafting

    Directory of Open Access Journals (Sweden)

    Magdy Kandil Zahran


    Full Text Available This paper describes a new method for the grafting of methacrylic acid (MAA and other acrylic monomers onto wool fabric in aqueous medium. The novelty principally concerns the chemical approach of the redox grafting reaction that was carried out in the presence of sodium perborate (SPB initiator. Before the grafting reaction was started, the wool fabric was treated first with a freshly prepared ferrous ammonium sulfate (FAS solution. The so-treated fabric formed, with SPB, an efficacious redox system capable of initiating grafting of methacrylic acid (MAA and other acrylic monomers onto the wool fabric. The effect of the polymerization conditions on the polymer criteria, namely, graft yield (%GY, homopolymer (%HP, total conversion (%TC, and grafting efficiency (%GE, was studied. These polymer criteria were found to depend spaciously upon concentrations of the Fe2+ ion (activator, SPB (initiator, and MAA, pH of the polymerization medium, duration and temperature of polymerization. The graft copolymerization reaction has also been carried out in the presence of polymerization activators (e.g. reductant transition metal ions and an inhibitor (e.g. hydroquinone. A suitable mechanism for the grafting processes has been suggested, in accordance with the experimental results.

  7. Multimodality imaging of coronary artery bypass grafts

    NARCIS (Netherlands)

    Salm, Liesbeth Pauline


    This thesis describes multiple imaging modalities to examine coronary artery bypass grafts, and the research which was performed to further develop noninvasive imaging techniques to detect stenoses in native coronary arteries and bypass grafts in patients who experienced recurrent chest pain after c

  8. Coaxial electrospinning multicomponent functional controlled-release vascular graft: Optimization of graft properties. (United States)

    Yin, Anlin; Luo, Rifang; Li, Jiukai; Mo, Xiumei; Wang, Yunbing; Zhang, Xingdong


    Small diameter vascular grafts possessing desirable biocompatibility and suitable mechanical properties have become an urgent clinic demand. Herein, heparin loaded fibrous grafts of collagen/chitosan/poly(l-lactic acid-co-ε-caprolactone) (PLCL) were successfully fabricated via coaxial electrospinning. By controlling the concentration of heparin and the ratio of collagen/chitosan/PLCL, most grafts had the heparin encapsulation efficiency higher than 70%, and the heparin presented sustained release for more than 45 days. Particularly, such multicomponent grafts had relative low initial burst release, and after heparin releasing for 3 weeks, the grafts still showed good anti-platelet adhesion ability. In addition, along with the excellent cell biocompatibility, the fabricated grafts possessed suitable mechanical properties including good tensile strength, suture retention strength, burst pressure and compliance which could well match the native blood vessels. Thus, the optimized graft properties could be properly addressed for vascular tissue application via coaxial electrospinning.

  9. Site-directed mutagenesis of the cAMP-binding sites of the recombinant type I regulatory subunit of cAMP-dependent protein kinase. (United States)

    Kuno, T; Shuntoh, H; Sakaue, M; Saijoh, K; Takeda, T; Fukuda, K; Tanaka, C


    The type I regulatory subunit (R-I) of rat brain cAMP-dependent protein kinase was expressed in E. coli and site-directed mutagenesis was used to substitute amino acids in the putative cAMP-binding sites. The wild-type recombinant R-I bound 2 mol of cAMP/mol subunit, while two mutant R-Is with a single amino acid substitution in one of the two intrachain cAMP-binding sites (clone N153:a glutamate for Gly-200, and clone C254:an aspartate for Gly-324) bound 1 mol of cAMP/mol subunit. When these two substitutions were made in one mutant, cAMP did not bind to this mutant, indicating that binding of cAMP to N153 or C254 was to their nonmutated sites. Competition experiments with site-selective analogs and dissociation of bound cAMP from mutant R-Is provided evidence for strong intrachain interactions between the two classes of cAMP-binding sites in R-I.

  10. Polyethylene oxide hydration in grafted layers (United States)

    Dormidontova, Elena; Wang, Zilu

    Hydration of water soluble polymers is one of the key-factors defining their conformation and properties, similar to biopolymers. Polyethylene oxide (PEO) is one of the most important biomedical-applications polymers and is known for its reverse temperature solubility due to hydrogen bonding with water. As in many practical applications PEO chains are grafted to surfaces, e.g. of nanoparticles or planar surfaces, it is important to understand PEO hydration in such grafted layers. Using atomistic molecular dynamic simulations we investigate the details of molecular conformation and hydration of PEO end-grafted to gold surfaces. We analyze polymer and water density distribution as a function of distance from the surface for different grafting densities. Based on a detailed analysis of hydrogen bonding between polymer and water in grafted PEO layers, we will discuss the extent of PEO hydration and its implication for polymer conformation, mobility and layer properties. This research is supported by NSF (DMR-1410928).

  11. Graft Take-Rates After Tympanoplasty

    DEFF Research Database (Denmark)

    Andersen, Steven Arild Wuyts; Aabenhus, Kristine; Glad, Henrik;


    , technique, graft material, and revision surgery) for tympanoplasty type I were studied. A comparison with the graft take-rates for tympanoplasty types II to IV and/or cholesteatoma was made. RESULTS: A user-friendly ear surgery database with fast data entry and direct import of audiometric data......OBJECTIVE: To present a prospective ear surgery database and investigate the graft take-rate and prognostic factors for graft take-rate in tympanoplasty using the database. STUDY DESIGN: Prospective database study. SETTING: Tertiary referral center. PATIENTS: A total of 1606 cases undergoing...... tympanoplasty types I to IV were registered in the database in the period from February 2004 to November 2013. INTERVENTION: A total of 837 cases underwent myringoplasty/tympanoplasty type I. MAIN OUTCOME MEASURE: Graft take-rate and prognostic factors (age, discharge at time of surgery, tuba function...

  12. Novel cAMP signalling paradigms: therapeutic implications for airway disease


    Billington, Charlotte K; Hall, Ian P


    Since its discovery over 50 years ago, cAMP has been the archetypal second messenger introducing students to the concept of cell signalling at the simplest level. As explored in this review, however, there are many more facets to cAMP signalling than the path from Gs-coupled receptor to adenylyl cyclase (AC) to cAMP to PKA to biological effect. After a brief description of this canonical cAMP signalling pathway, a snapshot is provided of the novel paradigms of cAMP signalling. As in the airwa...

  13. Inactivation of Multidrug Resistance Proteins Disrupts Both Cellular Extrusion and Intracellular Degradation of cAMP


    Xie, Moses; Rich, Thomas C.; Scheitrum, Colleen; Conti, Marco; Richter, Wito


    In addition to xenobiotics and several other endogenous metabolites, multidrug-resistance proteins (MRPs) extrude the second-messenger cAMP from various cells. Pharmacological and/or genetic inactivation of MRPs has been shown to augment intracellular cAMP signaling, an effect assumed to be a direct consequence of the blockade of cAMP extrusion. Here we provide evidence that the augmented intracellular cAMP levels are not due exclusively to the prevention of cAMP efflux because MRP inactivati...

  14. Persistent telomere cohesion triggers a prolonged anaphase. (United States)

    Kim, Mi Kyung; Smith, Susan


    Telomeres use distinct mechanisms (not used by arms or centromeres) to mediate cohesion between sister chromatids. However, the motivation for a specialized mechanism at telomeres is not well understood. Here we show, using fluorescence in situ hybridization and live-cell imaging, that persistent sister chromatid cohesion at telomeres triggers a prolonged anaphase in normal human cells and cancer cells. Excess cohesion at telomeres can be induced by inhibition of tankyrase 1, a poly(ADP-ribose) polymerase that is required for resolution of telomere cohesion, or by overexpression of proteins required to establish telomere cohesion, the shelterin subunit TIN2 and the cohesin subunit SA1. Regardless of the method of induction, excess cohesion at telomeres in mitosis prevents a robust and efficient anaphase. SA1- or TIN2-induced excess cohesion and anaphase delay can be rescued by overexpression of tankyrase 1. Moreover, we show that primary fibroblasts, which accumulate excess telomere cohesion at mitosis naturally during replicative aging, undergo a similar delay in anaphase progression that can also be rescued by overexpression of tankyrase 1. Our study demonstrates that there are opposing forces that regulate telomere cohesion. The observation that cells respond to unresolved telomere cohesion by delaying (but not completely disrupting) anaphase progression suggests a mechanism for tolerating excess cohesion and maintaining telomere integrity. This attempt to deal with telomere damage may be ultimately futile for aging fibroblasts but useful for cancer cells.

  15. Prolonging sensor networks lifetime using convex clusters

    Directory of Open Access Journals (Sweden)

    Payam Salehi


    Full Text Available Reducing the energy consumption of nodes in sensor networks and prolonging the network life time has been proposed as one of the most important challenges facing researchers in the field of sensor networks. Therefore, designing an energy-aware protocol to gather data from network level and transmitting it to sink is placed on the agenda at this paper. After presenting an analysis of the processes of clustering in sensory networks and investigating the effect of sending interval on the amount of energy consumption, We have shown that if the use of convex static casters be done such as all the communications within the cluster with the sending distance less than the optimal threshold, it Will help to increase the lifetime of nodes. also have shown that if we create a virtual backbone between cluster heads to transfer far cluster heads data from sink to sink , will has a significant impact on increasing the network lifetime. For this reason, a detailed discussion on how to determine the size of clusters and partitioning of the network environment to them is presented in Chapter 4.Simulation results show considerable improvement of the proposed algorithm.

  16. Prolonged cholestasis and ductopenia associated with tenoxicam. (United States)

    Trak-Smayra, Viviane; Cazals-Hatem, Dominique; Asselah, Tarik; Duchatelle, Veronique; Degott, Claude


    Cholestatic liver diseases leading to progressive destruction of intra-hepatic bile ducts and ductopenia encompass multiple etiologies. Pathophysiology and natural history of drug-induced cholangiopathies remain unclear. We report a case of prolonged ductopenia attributed to Tenoxicam (Tilcotil o--a non-steroidal anti-inflammatory drug of the oxicam family) ingested at therapeutic dose. A 36 year-old male patient was admitted for jaundice and Lyell syndrome starting 1 week after the ingestion of Tenoxicam. Liver biopsy showed cholestasis, non-suppurative cholangitis and polymorphous inflammatory infiltrate of the portal tracts (round cells, macrophages an eosinophils). Treatment with ursodesoxycholic acid and cholestyramine was instituted and the patient was asymptomatic 1 year after. Three years later mild biological cholestasis persisted and ductopenia was evidenced on liver biopsy. In this report we found that: (1) The toxicity of tenoxicam was probably mediated by an immunoallergic mechanism (Lyell syndrome and eosinophils on histology); (2) ductopenia was secondary to inflammatory cholangitis. Factors responsible for this chronic evolution are still unknown (genetic predisposition, vascular factors, etc.); and (3) the presence of ductopenia contrasted with the "clinical recovery" of the disease suggesting accessory bile drainage by cholangioles or partial reconstruction of the biliary tree.

  17. Suppression of Virulence of Toxigenic Vibrio cholerae by Anethole through the Cyclic AMP (cAMP)-cAMP Receptor Protein Signaling System. (United States)

    Zahid, M Shamim Hasan; Awasthi, Sharda Prasad; Asakura, Masahiro; Chatterjee, Shruti; Hinenoya, Atsushi; Faruque, Shah M; Yamasaki, Shinji


    Use of natural compounds as antivirulence drugs could be an alternative therapeutic approach to modify the outcome of bacterial infections, particularly in view of growing resistance to available antimicrobials. Here, we show that sub-bactericidal concentration of anethole, a component of sweet fennel seed, could suppress virulence potential in O1 El Tor biotype strains of toxigenic Vibrio cholerae, the causative agent of the ongoing 7th cholera pandemic. The expression of cholera toxin (CT) and toxin coregulated pilus (TCP), the major virulence factors of V. cholerae, is controlled through a regulatory cascade involving activation of ToxT with synergistic coupling interaction of ToxR/ToxS with TcpP/TcpH. We present evidence that anethole inhibits in vitro expression of CT and TCP in a toxT-dependent but toxR/toxS-independent manner and through repression of tcpP/tcpH, by using bead-ELISA, western blotting and quantitative real-time RT-PCR assays. The cyclic AMP (cAMP)-cAMP receptor protein (CRP) is a well-studied global signaling system in bacterial pathogens, and this complex is known to suppress expression of tcpP/tcpH in V. cholerae. We find that anethole influences the virulence regulatory cascade by over-expressing cyaA and crp genes. Moreover, suppression of toxigenic V. cholerae-mediated fluid accumulation in ligated ileum of rabbit by anethole demonstrates its potentiality as an antivirulence drug candidate against the diseases caused by toxigenic V. cholerae. Taken altogether, these results revealing a mechanism of virulence inhibition in V. cholerae by the natural compound anethole, may have relevance in designing antivirulence compounds, particularly against multiple antibiotic resistant bacterial pathogens.

  18. Expression profiles of antimicrobial peptides (AMPs) and their regulation by Relish (United States)

    Wang, Dongdong; Li, Fuhua; Li, Shihao; Wen, Rong; Xiang, Jianhai


    Antimicrobial peptides (AMPs), as key immune effectors, play important roles in the innate immune system of invertebrates. Different types of AMPs, including Penaeidin, Crustin, ALF (antilipopolysaccharide factor) have been identified in different penaeid shrimp; however, systematic analyses on the function of different AMPs in shrimp responsive to different types of bacteria are very limited. In this study, we analyzed the expression profiles of AMPs in the Chinese shrimps, Fenneropenaeus chinensis, simultaneously by real-time RT-PCR (reverse transcription-polymerase chain reaction) when shrimp were challenged with Micrococcus lysodeikticus (Gram-positive, G+) or Vibrio anguillarium (Gram-negative, G-). Different AMPs showed different expression profiles when shrimp were injected with one type of bacterium, and one AMP also showed different expression profiles when shrimp were challenged with different bacteria. Furthermore, the expression of these AMPs showed temporal expression profiles, suggesting that different AMPs function coordinately in bacteria-infected shrimp. An RNA interference approach was used to study the function of the Relish transcription factor in regulating the transcription of different AMPs. The current study showed that Relish could regulate the transcription of different AMPs in shrimp. Differential expression profiles of AMPs in shrimp injected with different types of bacteria indicated that a complicated antimicrobial response network existed in shrimp. These data contribute to our understanding of immunity in shrimp and may provide a strategy for the control of disease in shrimp.

  19. cAMP Signals in Drosophila Motor Neurons Are Confined to Single Synaptic Boutons

    Directory of Open Access Journals (Sweden)

    Isabella Maiellaro


    Full Text Available The second messenger cyclic AMP (cAMP plays an important role in synaptic plasticity. Although there is evidence for local control of synaptic transmission and plasticity, it is less clear whether a similar spatial confinement of cAMP signaling exists. Here, we suggest a possible biophysical basis for the site-specific regulation of synaptic plasticity by cAMP, a highly diffusible small molecule that transforms the physiology of synapses in a local and specific manner. By exploiting the octopaminergic system of Drosophila, which mediates structural synaptic plasticity via a cAMP-dependent pathway, we demonstrate the existence of local cAMP signaling compartments of micrometer dimensions within single motor neurons. In addition, we provide evidence that heterogeneous octopamine receptor localization, coupled with local differences in phosphodiesterase activity, underlies the observed differences in cAMP signaling in the axon, cell body, and boutons.

  20. Prevalence and molecular characterization of clinical isolates of Escherichia coli expressing an AmpC phenotype

    DEFF Research Database (Denmark)

    Jørgensen, Rikke Lind; Nielsen, Jesper Boye; Friis-Møller, Alice


    OBJECTIVES: To establish the prevalence of the AmpC beta-lactamase phenotype in clinical isolates of Escherichia coli and characterize the genetic resistance mechanisms causing the observed phenotype. METHODS: Clinical E. coli (n = 74) with reduced susceptibility to third-generation cephalosporins...... and resistance to cefoxitin were collected from the Department of Clinical Microbiology at Hvidovre Hospital, Denmark, in 2006. The AmpC disc test was used to confirm expression of AmpC, and test-positive strains were selected for further antimicrobial susceptibility testing and molecular characterization....... Hyperproduction of AmpC beta-lactamase was confirmed by isoelectric focusing (IEF). The presence of a plasmid-mediated ampC gene (pAmpC) was detected by multiplex PCR. The promoter and the entire reading frame of the chromosomal ampC gene were sequenced to identify promoter mutations associated...

  1. Grafting molecularly imprinted poly(2-acrylamido-2-methylpropanesulfonic acid) onto the surface of carbon microspheres

    Energy Technology Data Exchange (ETDEWEB)

    Yang Yongzhen [Key Laboratory of Interface Science and Engineering in Advanced Materials, Taiyuan University of Technology, Ministry of Education, Taiyuan 030024 (China); Research Center on Advanced Materials Science and Technology, Taiyuan University of Technology, Taiyuan 030024 (China); Zhang Yan; Li Sha [Key Laboratory of Interface Science and Engineering in Advanced Materials, Taiyuan University of Technology, Ministry of Education, Taiyuan 030024 (China); College of Chemistry and Chemical Engineering, Taiyuan University of Technology, Taiyuan 030024 (China); Liu Xuguang, E-mail: [Key Laboratory of Interface Science and Engineering in Advanced Materials, Taiyuan University of Technology, Ministry of Education, Taiyuan 030024 (China); College of Chemistry and Chemical Engineering, Taiyuan University of Technology, Taiyuan 030024 (China); Xu Bingshe [Key Laboratory of Interface Science and Engineering in Advanced Materials, Taiyuan University of Technology, Ministry of Education, Taiyuan 030024 (China); Research Center on Advanced Materials Science and Technology, Taiyuan University of Technology, Taiyuan 030024 (China)


    Poly(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) was grafted on the surface of carbon microspheres (CMSs), which were modified in prior by a mixed acid (HNO{sub 3} and H{sub 2}SO{sub 4}) oxidation and 3-methacryloxypropyl trimethoxysilane silanization. Then, the molecularly imprinting polymerization was carried out towards the macromolecule PAMPS grafted on the surface of CMSs using dibenzothiophene (DBT) as template, ethylene dimethacrylate as cross-linking agent and (NH{sub 4}){sub 2}S{sub 2}O{sub 8} (APS) as initiator to prepare surface molecularly imprinted polymer (MIP-PAMPS/CMSs) for adsorbing DBT. The optimized conditions of grafting PAMPS, including AMPS dosage, APS content, reaction temperature and reaction time, were emphasized in this paper. The morphology of the samples was characterized by field emission scanning electron microscopy. The functional groups were analyzed qualitatively by Fourier transform infrared spectrometry. The grafting degree of PAMPS was investigated by thermogravimetry. The results show that the preferable AMPS dosage, APS content, reaction temperature and time were 5 g, 0.15 g, 70 Degree-Sign C and 12 h, respectively, for preparing PAMPS/CMSs composite on the basis of 1.0 g of silanized-CMSs. The absorbing characteristic of MIP-PAMPS/CMSs toward DBT was studied preliminarily with dynamic adsorption. In the experiment of dynamic adsorption, MIP-PAMPS/CMSs and non-imprinted polymer (NIP-PAMPS/CMSs) were compared with respect to their rapid adsorption in 1 mmol/L of DBT solution in n-hexane. When the first 1 mL of 1 mmol/L DBT solution was injected and flowed through a column packed with 0.1 g of MIP-PAMPS/CMSs, the content of DBT reduced to 0.265 mmol/L, that is, decreased significantly from 279 to 74 ppm. When 3 mL of DBT solution was flowed through the packed column, the adsorption of MIP-PAMPS/CMSs toward DBT reached saturation with the maximum adsorption amount of 1.38 Multiplication-Sign 10{sup -2} mmol/g and the

  2. Grafting molecularly imprinted poly(2-acrylamido-2-methylpropanesulfonic acid) onto the surface of carbon microspheres (United States)

    Yang, Yongzhen; Zhang, Yan; Li, Sha; Liu, Xuguang; Xu, Bingshe


    Poly(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) was grafted on the surface of carbon microspheres (CMSs), which were modified in prior by a mixed acid (HNO3 and H2SO4) oxidation and 3-methacryloxypropyl trimethoxysilane silanization. Then, the molecularly imprinting polymerization was carried out towards the macromolecule PAMPS grafted on the surface of CMSs using dibenzothiophene (DBT) as template, ethylene dimethacrylate as cross-linking agent and (NH4)2S2O8 (APS) as initiator to prepare surface molecularly imprinted polymer (MIP-PAMPS/CMSs) for adsorbing DBT. The optimized conditions of grafting PAMPS, including AMPS dosage, APS content, reaction temperature and reaction time, were emphasized in this paper. The morphology of the samples was characterized by field emission scanning electron microscopy. The functional groups were analyzed qualitatively by Fourier transform infrared spectrometry. The grafting degree of PAMPS was investigated by thermogravimetry. The results show that the preferable AMPS dosage, APS content, reaction temperature and time were 5 g, 0.15 g, 70 °C and 12 h, respectively, for preparing PAMPS/CMSs composite on the basis of 1.0 g of silanized-CMSs. The absorbing characteristic of MIP-PAMPS/CMSs toward DBT was studied preliminarily with dynamic adsorption. In the experiment of dynamic adsorption, MIP-PAMPS/CMSs and non-imprinted polymer (NIP-PAMPS/CMSs) were compared with respect to their rapid adsorption in 1 mmol/L of DBT solution in n-hexane. When the first 1 mL of 1 mmol/L DBT solution was injected and flowed through a column packed with 0.1 g of MIP-PAMPS/CMSs, the content of DBT reduced to 0.265 mmol/L, that is, decreased significantly from 279 to 74 ppm. When 3 mL of DBT solution was flowed through the packed column, the adsorption of MIP-PAMPS/CMSs toward DBT reached saturation with the maximum adsorption amount of 1.38 × 10-2 mmol/g and the overall adsorption efficiency of 46%, while NIP-PAMPS/CMSs adsorbed only 1.66

  3. Design of Low Voltage Low Power CMOS OP-AMP

    Directory of Open Access Journals (Sweden)

    Shahid Khan,


    Full Text Available Operational amplifiers are an integral part of many analog and mixed signal systems. As the demand for mixed mode integrated circuits increases, the design of analog circuits such as operational amplifiers in CMOS technology becomes more critical. This paper presents a two stage CMOS operational amplifier, which operates at ±1.8V power supply using TSMC 0.18um CMOS technology. The OP-AMP designed exhibit unity gain frequency of 12.6 MHz, and gain of 55.5db with 300uw power dissipation. The gain margin and phase margin of OP-AMP is 45˚ and 60˚ respectively. Design and simulation has been carried out in P Spice tool.

  4. Aerobic Methane Generation From Plants (AMP)? Yes, Mostly! (United States)

    Whiticar, M. J.; Ednie, A. C.


    In 2006, Keppler et al. (K) published an intriguing and revolutionary idea that aerobic methane is produced in plants (AMP) and released to the atmosphere. Their initial scaling calculations estimated the amount of AMP fluxing from living plants to range from 62-236 Tg/y and 1-7 Tg/y for plant litter. Houweling et al. (2006) (H) refined this flux to ca. 85 Tg/y PIH and 125 Tg/y present day. More recently, Dueck et al. (2007) (D) challenged the claim of AMP from intact plants. Their experiments cited "...No evidence for substantial aerobic methane emission by terrestrial plants..." (max. 0.4 ng/g h-1). Due to the significance of AMP in understanding present and palaeo-atmospheric budgets (e.g., Whiticar and Schaefer, 2007), we conducted a wide range of experiments to confirm or refute the existence and magnitude of AMP. For explanation, experiments of K were time-series batch samples measured by gas chromatography on purged and ambient samples, whereas D used continuous-flow cuvettes and measured by optical PAS with time series single injections. Our longer-term experiments with corn, wheat, tomato, red cedar, chestnut, moss and lichen (3-97 h, 32 °C) used a plant chamber, flow-through system with a GYRO, an optical spectrometer that enables continuous 1 Hz CH4 measurements with a precision of ca. 1 ppbv. We conducted over 100 chamber experiments on sterilized and non-sterilized (Cs-137 radiation) samples of: 1) intact living plants (IP), 2) fresh leaves (FL) and 3) dried leaves (DL); under both 1) high and 2) low light conditions (HL, LL), and with 1) ambient CH4 (AM, ca. 1.92 ppmv) and 2) purged methane (PM, 10 and 96 ppbv) levels. Our results demonstrate that IP-AMs have CH4 flux rates of 0.74-3.48 ng/g h-1. In contrast, IP-PMs show intense CH4 uptake rates of -28.5 to -57.9 ng/g h-1 (substantially different than K's reported emissions of 12-370 ng/g h-1 values). Our FL-AM-LL have CH4 flux rates of 0.36-2.05 ng/g h-1, whereas FL-AM-HL have significant CH4

  5. Three-dimensional measurement of cAMP gradients using hyperspectral confocal microscopy (United States)

    Rich, Thomas C.; Annamdevula, Naga; Britain, Andrea L.; Mayes, Samuel; Favreau, Peter F.; Leavesley, Silas J.


    Cyclic AMP (cAMP) is a ubiquitous second messenger known to differentially regulate many cellular functions over a wide range of timescales. Several lines of evidence have suggested that the distribution of cAMP within cells is not uniform, and that cAMP compartmentalization is largely responsible for signaling specificity within the cAMP signaling pathway. However, to date, no studies have experimentally measured three dimensional (3D) cAMP distributions within cells. Here we use both 2D and 3D hyperspectral microscopy to visualize cAMP gradients in endothelial cells from the pulmonary microvasculature (PMVECs). cAMP levels were measured using a FRETbased cAMP sensor comprised of a cAMP binding domain from EPAC sandwiched between FRET donors and acceptors -- Turquoise and Venus fluorescent proteins. Data were acquired using either a Nikon A1R spectral confocal microscope or custom spectral microscopy system. Analysis of hyperspectral image stacks from a single confocal slice or from summed images of all slices (2D analysis) indicated little or no cAMP gradients were formed within PMVECs under basal conditions or following agonist treatment. However, analysis of hyperspectral image stacks from 3D cellular geometries (z stacks) demonstrate marked cAMP gradients from the apical to basolateral membrane of PMVECs. These results strongly suggest that 2D imaging studies of cAMP compartmentalization -- whether epifluorescence or confocal microscopy -- may lead to erroneous conclusions about the existence of cAMP gradients, and that 3D studies are required to assess mechanisms of signaling specificity.

  6. Lipid metabolism disturbances and AMPK activation in prolonged propofol-sedated rabbits under mechanical ventilation

    Institute of Scientific and Technical Information of China (English)

    Wei JIANG; Zheng-bo YANG; Quan-hong ZHOU; Xiang HUAN; Li WANG


    To explore the mechanisms underlying the propofol infusion syndrome (PRIS),a potentially fatal complication during prolonged propofol infusion.Methods:Male rabbits urider mechanical ventilation through endotracheal intubation were divided into 3 groups (n=6 for each) that were sedated with 1% propofol (Group P),isoflurane (Group Ⅰ) or isoflurane while receiving 10% intralipid (Group Ⅱ),respectively.Blood biochemical parameters were collected at O,6,12,18,24,and 30-36 h after the initiation of treatments.The hearts were removed out immediately after the experiments,and the level of tumor necrosis factor (TNF)-α in the hearts were studied using immunohistochemistry.AMP-activated protein kinase (AMPK) and phospho-AMPK in the hearts were assessed using Western blotting.Results:The mortality rate was 50% in Group P,and 0% in Groups Ⅰ and Ⅱ.The serum lipids and liver function indices in Group P were significantly increased,but moderately increased in Group Ⅱ.Significant decreases in these indices were found in Groups Ⅰ.All the groups showed dramatically increased release of creatine kinase (CK).Intense positive staining of TNF-c was found in all the heart samples in Group P,but only weak and neglectful staining was found in the hearts from Group Ⅱ and Group Ⅰ,respectively.AMPK phosphorylation was significantly increased in the hearts of Group P.Conclusion:Continuous infusion of large dose of propofol in rabbits undergoing prolonged mechanical ventilation causes hyperlipidemia,liver dysfunction,increased CK levels,AMPK activation and myocardial injury.The imbalance between energy demand and utilization may contribute to PRIS.

  7. Exceptionally prolonged tooth formation in elasmosaurid plesiosaurians (United States)

    Kear, Benjamin P.; Larsson, Dennis; Lindgren, Johan; Kundrát, Martin


    Elasmosaurid plesiosaurians were globally prolific marine reptiles that dominated the Mesozoic seas for over 70 million years. Their iconic body-plan incorporated an exceedingly long neck and small skull equipped with prominent intermeshing ‘fangs’. How this bizarre dental apparatus was employed in feeding is uncertain, but fossilized gut contents indicate a diverse diet of small pelagic vertebrates, cephalopods and epifaunal benthos. Here we report the first plesiosaurian tooth formation rates as a mechanism for servicing the functional dentition. Multiple dentine thin sections were taken through isolated elasmosaurid teeth from the Upper Cretaceous of Sweden. These specimens revealed an average of 950 daily incremental lines of von Ebner, and infer a remarkably protracted tooth formation cycle of about 2–3 years–other polyphyodont amniotes normally take ~1–2 years to form their teeth. Such delayed odontogenesis might reflect differences in crown length and function within an originally uneven tooth array. Indeed, slower replacement periodicity has been found to distinguish larger caniniform teeth in macrophagous pliosaurid plesiosaurians. However, the archetypal sauropterygian dental replacement system likely also imposed constraints via segregation of the developing tooth germs within discrete bony crypts; these partly resorbed to allow maturation of the replacement teeth within the primary alveoli after displacement of the functional crowns. Prolonged dental formation has otherwise been linked to tooth robustness and adaption for vigorous food processing. Conversely, elasmosaurids possessed narrow crowns with an elongate profile that denotes structural fragility. Their apparent predilection for easily subdued prey could thus have minimized this potential for damage, and was perhaps coupled with selective feeding strategies that ecologically optimized elasmosaurids towards more delicate middle trophic level aquatic predation. PMID:28241059

  8. Fatigue associated with prolonged graded running. (United States)

    Giandolini, Marlene; Vernillo, Gianluca; Samozino, Pierre; Horvais, Nicolas; Edwards, W Brent; Morin, Jean-Benoît; Millet, Guillaume Y


    Scientific experiments on running mainly consider level running. However, the magnitude and etiology of fatigue depend on the exercise under consideration, particularly the predominant type of contraction, which differs between level, uphill, and downhill running. The purpose of this review is to comprehensively summarize the neurophysiological and biomechanical changes due to fatigue in graded running. When comparing prolonged hilly running (i.e., a combination of uphill and downhill running) to level running, it is found that (1) the general shape of the neuromuscular fatigue-exercise duration curve as well as the etiology of fatigue in knee extensor and plantar flexor muscles are similar and (2) the biomechanical consequences are also relatively comparable, suggesting that duration rather than elevation changes affects neuromuscular function and running patterns. However, 'pure' uphill or downhill running has several fatigue-related intrinsic features compared with the level running. Downhill running induces severe lower limb tissue damage, indirectly evidenced by massive increases in plasma creatine kinase/myoglobin concentration or inflammatory markers. In addition, low-frequency fatigue (i.e., excitation-contraction coupling failure) is systematically observed after downhill running, although it has also been found in high-intensity uphill running for different reasons. Indeed, low-frequency fatigue in downhill running is attributed to mechanical stress at the interface sarcoplasmic reticulum/T-tubule, while the inorganic phosphate accumulation probably plays a central role in intense uphill running. Other fatigue-related specificities of graded running such as strategies to minimize the deleterious effects of downhill running on muscle function, the difference of energy cost versus heat storage or muscle activity changes in downhill, level, and uphill running are also discussed.

  9. Encephalitis with Prolonged but Reversible Splenial Lesion

    Directory of Open Access Journals (Sweden)

    Alena Meleková


    Full Text Available Introduction: The splenium of the corpus callosum has a specific structure of blood supply with a tendency towards blood-brain barrier breakdown, intramyelinic edema, and damage due to hypoxia or toxins. Signs and symptoms of reversible syndrome of the splenium of the corpus callosum typically include disorientation, confusion, impaired consciousness, and epileptic seizures. Case report: A previously healthy 32-year-old man suffered from weakness, headache, and fever. Subsequently, he developed apathy, ataxia, and inability to walk, and therefore was admitted to the hospital. Cerebrospinal fluid showed protein elevation (0.9 g/l and pleocytosis (232/1 ul. A brain MRI showed hyperintense lesions in the middle of the corpus callosum. The patient was treated with antibiotics, and subsequently, in combination with steroids. Two months later, the hyperintense lesions in the splenium and the basal ganglia had disappeared. Almost seven months since his hospitalization in the Department of Neurology, the patient has returned to his previous employment. He now does not exhibit any mental changes, an optic edema and urological problems have improved. In addition, he is now actively engaged in sports. Conclusion: We have described a case of a 32-year-old man with confusion, ataxia, and inability to stand and walk. The man developed a febrile meningeal syndrome and a hyperintense lesion of the splenium, which lasted for two months. Neurological changes, optic nerve edema, and urinary retention have resolved over the course of seven months. We think that the prolonged but transient lesion of the splenium may have been caused by encephalitis of viral origin.

  10. Software Design Document for the AMP Nuclear Fuel Performance Code

    Energy Technology Data Exchange (ETDEWEB)

    Philip, Bobby [ORNL; Clarno, Kevin T [ORNL; Cochran, Bill [ORNL


    The purpose of this document is to describe the design of the AMP nuclear fuel performance code. It provides an overview of the decomposition into separable components, an overview of what those components will do, and the strategic basis for the design. The primary components of a computational physics code include a user interface, physics packages, material properties, mathematics solvers, and computational infrastructure. Some capability from established off-the-shelf (OTS) packages will be leveraged in the development of AMP, but the primary physics components will be entirely new. The material properties required by these physics operators include many highly non-linear properties, which will be replicated from FRAPCON and LIFE where applicable, as well as some computationally-intensive operations, such as gap conductance, which depends upon the plenum pressure. Because there is extensive capability in off-the-shelf leadership class computational solvers, AMP will leverage the Trilinos, PETSc, and SUNDIALS packages. The computational infrastructure includes a build system, mesh database, and other building blocks of a computational physics package. The user interface will be developed through a collaborative effort with the Nuclear Energy Advanced Modeling and Simulation (NEAMS) Capability Transfer program element as much as possible and will be discussed in detail in a future document.

  11. Preparation of Cross-linking Copolymerization of Chitosan and AMPS in Ionic Liquid%离子液体中壳聚糖/AMPS共聚交联微球的制备

    Institute of Scientific and Technical Information of China (English)

    张聪璐; 胡筱敏; 侯晓虹; 陶颖婷


    Cross-linking copolymerization of 2-acrylamide-2-methylpro panesulfonic acid (AMPS) and chitosan in ionic liquid was studied using ceric ammonium nitrate (CAN) as an initiator, p-benzoquinone as resistance polymerization retarder, and glycine hydrochloride ionic liquid water solution as reaction medium. The obtained product was characterized by SEM, FTIR and TGA. The results showed that, the reaction rate and grafting ratio were improved greatly by [Gly]Cl as reaction medium. The obtained product was regular spherical , the particle diameter was about 2 μm. And the product had smooth surface, some resistance to acid and alkali.

  12. Grafted dopamine neurons: Morphology, neurochemistry, and electrophysiology. (United States)

    Strömberg, Ingrid; Bickford, Paula; Gerhardt, Greg A


    Grafting of dopamine-rich tissue to counteract the symptoms in Parkinson's disease became a promising tool for future treatment. This article discusses how to improve the functional outcome with respect to graft outgrowth and functions of dopamine release and electrophysiological responses to graft implantation in the host brain striatal target. It has been documented that a subpopulation of the dopamine neurons innervates the host brain in a target-specific manner, while some of the grafted dopamine neurons never project to the host striatum. Neurochemical studies have demonstrated that the graft-induced outgrowth synthesize, store, metabolize and release dopamine and possibly other neurotransmitters such as 5-HT. Furthermore, the released dopamine affects the dopamine-depleted brain in areas that are larger than the graft-derived nerve fibers reach. While stem cells will most likely be the future source of cells to be used in grafting, it is important to find the guiding cues for how to reinnervate the dopamine-depleted striatum in a proper way with respect to the dopamine subpopulations of A9 and A10 to efficiently treat the motor abnormalities seen in Parkinson's disease.

  13. Fetal hippocampal CA3 cell grafts enriched with FGF-2 and BDNF exhibit robust long-term survival and integration and suppress aberrant mossy fiber sprouting in the injured middle-aged hippocampus. (United States)

    Rao, Muddanna S; Hattiangady, Bharathi; Shetty, Ashok K


    Cell transplants that successfully replace the lost neurons and facilitate the reconstruction of the disrupted circuitry in the injured aging hippocampus are invaluable for treating acute head injury, stroke and status epilepticus in the elderly. This is because apt graft integration has the potential to prevent the progression of the acute injury into chronic epilepsy in the elderly. However, neural transplants into the injured middle-aged or aged hippocampus exhibit poor cell survival, suggesting that apt graft augmentation strategies are critical for robust integration of grafted cells into the injured aging hippocampus. We examined the efficacy of pre-treatment and grafting of donor fetal CA3 cells with a blend of fibroblast growth factor-2 (FGF-2) and brain-derived neurotrophic factor (BDNF) for lasting survival and integration of grafted cells in the injured middle-aged (12 months old) hippocampus of F344 rats. Grafts were placed at 4 days after the kainic-acid-induced hippocampal injury and were analyzed at 6 months post-grafting. We demonstrate that 80% of grafted cells exhibit prolonged survival and 71% of grafted cells differentiate into CA3 pyramidal neurons. Grafts also receive a robust afferent input from the host mossy fibers and project efferent axons into the denervated zones of the dentate gyrus and the CA1 subfield. Consequently, the aberrant sprouting of the dentate mossy fibers, an epileptogenic change that typically ensues after the hippocampal injury, was suppressed. Thus, grafts of fetal CA3 cells enriched with FGF-2 and BDNF exhibit robust integration and dampen the abnormal mossy fiber sprouting in the injured middle-aged hippocampus. Because the aberrantly sprouted mossy fibers contribute to the generation of seizures, the results suggest that the grafting intervention using FGF-2 and BDNF is efficacious for suppressing epileptogenesis in the injured middle-aged hippocampus.

  14. The role of cAMP in nerve growth factor-promoted neurite outgrowth in PC12 cells



    Nerve growth factor (NGF)-mediated neurite outgrowth in rat pheochromocytoma PC12 cells has been described to be synergistically potentiated by the simultaneous addition of dibutyryl cAMP. To elucidate further the role of cAMP in NGF-induced neurite outgrowth we have used the adenylate cyclase activator forskolin, cAMP, and a set of chemically modified cAMP analogues, including the adenosine cyclic 3',5'-phosphorothioates (cAMPS) (Rp)-cAMPS and (Sp)-cAMPS. These diastereomers have differentia...

  15. Exchange Protein Directly Activated by cAMP (epac) : A Multidomain cAMP Mediator in the Regulation of Diverse Biological Functions

    NARCIS (Netherlands)

    Schmidt, Martina; Dekker, Frank J.; Maarsingh, Harm


    Since the discovery nearly 60 years ago, cAMP is envisioned as one of the most universal and versatile second messengers. The tremendous feature of cAMP to tightly control highly diverse physiologic processes, including calcium homeostasis, metabolism, secretion, muscle contraction, cell fate, and g

  16. Hemodynamics Simulation of Stenosed Coronary Bypass Graft

    Institute of Scientific and Technical Information of China (English)

    LIU You-jun; QIAO Aike; DU Jian-jun


    By means of FEM, the physiological blood flow in coronary bypass graft is simulated. The stenosis in coronary artery is involved in the graft model,and the deformation of graft end to allow the surgical suture with a smaller diameter coronary is taken into consideration. The flow pattern, secondary flow and wall shear stress in the vicinity of anastomosis are analyzed. It is shown that a zone of low wall stress and high wall stress gradient exists downstream the toe. The floor opposed to the anastomosis is an area of high wall stress and high wall stress gradient. Both the toe downstream and the anastomosis bottom floor are prone to intimal hyperplasia.

  17. Flow characteristics in narrowed coronary bypass graft (United States)

    Bernad, S. I.; Bosioc, A.; Bernad, E. S.; Petre, I.; Totorean, A. F.


    Tortuous saphenous vein graft (SVG) hemodynamics was investigated using computational fluid dynamics (CFD) techniques. Computed tomography (CT) technology is used for non-invasive bypass graft assessment 7 days after surgery. CT investigation shown two regions with severe shape remodelling first is an elbow type contortion and second is a severe curvature with tortuous area reduction. In conclusion, the helical flow induced by vessel torsion may stabilize the blood flow in the distal part of the SVG, reducing the flow disturbance and suppressing the flow separation, but in the distal end of the graft, promote the inflammatory processes in the vessels.

  18. Opposing activity changes in AMP deaminase and AMP-activated protein kinase in the hibernating ground squirrel.

    Directory of Open Access Journals (Sweden)

    Miguel A Lanaspa

    Full Text Available Hibernating animals develop fatty liver when active in summertime and undergo a switch to a fat oxidation state in the winter. We hypothesized that this switch might be determined by AMP and the dominance of opposing effects: metabolism through AMP deaminase (AMPD2 (summer and activation of AMP-activated protein kinase (AMPK (winter. Liver samples were obtained from 13-lined ground squirrels at different times during the year, including summer and multiples stages of winter hibernation, and fat synthesis and β-fatty acid oxidation were evaluated. Changes in fat metabolism were correlated with changes in AMPD2 activity and intrahepatic uric acid (downstream product of AMPD2, as well as changes in AMPK and intrahepatic β-hydroxybutyrate (a marker of fat oxidation. Hepatic fat accumulation occurred during the summer with relatively increased enzymes associated with fat synthesis (FAS, ACL and ACC and decreased enoyl CoA hydratase (ECH1 and carnitine palmitoyltransferase 1A (CPT1A, rate limiting enzymes of fat oxidation. In summer, AMPD2 activity and intrahepatic uric acid levels were high and hepatic AMPK activity was low. In contrast, the active phosphorylated form of AMPK and β-hydroxybutyrate both increased during winter hibernation. Therefore, changes in AMPD2 and AMPK activity were paralleled with changes in fat synthesis and fat oxidation rates during the summer-winter cycle. These data illuminate the opposing forces of metabolism of AMP by AMPD2 and its availability to activate AMPK as a switch that governs fat metabolism in the liver of hibernating ground squirrel.

  19. Immunohistochemical localization of IAA in graft union of explanted internode grafting

    Institute of Scientific and Technical Information of China (English)


    The dynamic changes of IAA in graft union of explanted internode autografting of Cucumber (Cucumis sativus Linn.) have been investigated using the immunohistochemical localization technique.It is shown that the efficiency of IAA fixation using lyophilization-gas fixation is higher than that using liquid chemical fixation.In contrast to few silver particles and no significant changes during the development of graft union cultured in hormone-free medium,more silver particles in graft union and significant changes of IAA related to graft union development have been found when graft union was cultured in medium supplemented with appropriate hormones.The fixation procedure of plant hormones and the roles of IAA in graft union are discussed.

  20. A novel cysteine-rich antifungal peptide ToAMP4 from Taraxacum officinale Wigg. flowers. (United States)

    Astafieva, A A; Rogozhin, Eugene A; Andreev, Yaroslav A; Odintsova, T I; Kozlov, S A; Grishin, Eugene V; Egorov, Tsezi A


    A novel peptide named ToAMP4 was isolated from Taraxacum officinale Wigg. flowers by a combination of acetic acid extraction and different types of chromatography: affinity, size-exclusion, and RP-HPLC. The amino acid sequence of ToAMP4 was determined by automated Edman degradation. The peptide is basic, consists of 41 amino acids, and incorporates three disulphide bonds. Due to the unusual cysteine spacing pattern, ToAMP4 does not belong to any known plant AMP family, but classifies together with two other antimicrobial peptides ToAMP1 and ToAMP2 previously isolated from the dandelion flowers. To study the biological activity of ToAMP4, it was successfully produced in a prokaryotic expression system as a fusion protein with thioredoxin. The recombinant peptide was shown to be identical to the native ToAMP4 by chromatographic behavior, molecular mass, and N-terminal amino acid sequence. The peptide displays broad-spectrum antifungal activity against important phytopathogens. Two ToAMP4-mediated inhibition strategies depending on the fungus were demonstrated. The results obtained add to our knowledge on the structural and functional diversity of AMPs in plants.

  1. Expression profiles of antimicrobial peptides (AMPs) and their regulation by Relish

    Institute of Scientific and Technical Information of China (English)

    WANG Dongdong; LI Fuhua; LI Shihao; WEN Rong; XIANG Jianhai


    Antimicrobial peptides (AMPs),as key immune effectors,play important roles in the innate immune system of invertebrates.Different types of AMPs,including Penaeidin,Crustin,ALF (antilipopolysaccharide factor) have been identified in different penaeid shrimp; however,systematic analyses on the function of different AMPs in shrimp responsive to different types of bacteria are very limited.In this study,we analyzed the expression profiles of AMPs in the Chinese shrimps,Fenneropenaeus chinensis,simultaneously by real-time RT-PCR (reverse transcription-polymerase chain reaction) when shrimp were challenged with Micrococcus lysodeikticus (Gram-positive,G+) or Vibrio anguillarium (Gram-negative,G).Different AMPs showed different expression profiles when shrimp were injected with one type of bacterium,and one AMP also showed different expression profiles when shrimp were challenged with different bacteria.Furthermore,the expression of these AMPs showed temporal expression profiles,suggesting that different AMPs function coordinately in bacteria-infected shrimp.An RNA interference approach was used to study the function of the Relish transcription factor in regulating the transcription of different AM Ps.The current study showed that Relish could regulate the transcription of different AMPs in shrimp.Differential expression profiles of AMPs in shrimp injected with different types of bacteria indicated that a complicated antimicrobial response network existed in shrimp.These data contribute to our understanding of immunity in shrimp and may provide a strategy for the control of disease in shrimp.

  2. Epac and PKA: a tale of two intracellular cAMP receptors

    Institute of Scientific and Technical Information of China (English)

    Xiaodong Cheng; Zhenyu Ji; Tamara Tsalkova; Fang Mei


    cAMP-mediated signaling pathways regulate a multitude of important biological processes under both physiological and pathological conditions,including diabetes,heart failure and cancer.In eukaryotic cells,the effects of cAMP are mediated by two ubiquitously expressed intracellular cAMP receptors,the classic protein kinase A (PKA)/cAMP-dependent protein kinase and the recently discovered exchange protein directly activated by cAMP(Epac)/cAMP-regulated guanine nucleotide exchange factors.Like PKA,Epac contains an evolutionally conserved cAMP binding domain that acts as a molecular switch for sensing intracellular second messenger cAMP levels to control diverse biological functions.The existence of two families of cAMP effectors provides a mechanism for a more precise and integrated control of the cAMP signaling pathways in a spatial and temporal manner.Depending upon the specific cellular environments as well as their relative abundance,distrbution and localization,Epac and PKA may act independently,converge synergistically or oppose each other in regulating a specific cellular function.

  3. DHA-1型质粒AmpC酶调控因子AmpR基因检测%Detection of regulator AmpR genes of DHA-1 type plasmid-encoded AmpC β-lactamase in escherichia coli and klebsiella pnuemoniae isolates

    Institute of Scientific and Technical Information of China (English)

    多丽波; 栾英; 张联博; 李垚


    目的 检测DHA-1型质粒AmpC酶诱导性耐药调控因子AmpR基因.方法 以我院临床分离产DHA-1型质粒AmpC酶的4株大肠埃希菌和10株肺炎克雷伯菌为研究对象,采用聚合酶链反应(PCR),用特异性引物扩增AmpR调节因子全编码基因,并将一株肺炎克雷伯菌AmpR基因克隆到pET-22b(+)载体质粒中测序.结果 所有实验菌株AmpR基因检测阳性,重组子AmpR基因测序表明与摩根摩根菌染色体上AmpR基因同源性达99.8%.结论 产DHA-1型质粒AmpC酶肺炎克雷伯菌、大肠埃希菌的质粒上存在调控因子AmpR基因.

  4. AmpH, a bifunctional DD-endopeptidase and DD-carboxypeptidase of Escherichia coli. (United States)

    González-Leiza, Silvia M; de Pedro, Miguel A; Ayala, Juan A


    In Escherichia coli, low-molecular-mass penicillin-binding proteins (LMM PBPs) are important for correct cell morphogenesis. These enzymes display DD-carboxypeptidase and/or dd-endopeptidase activities associated with maturation and remodeling of peptidoglycan (PG). AmpH has been classified as an AmpH-type class C LMM PBP, a group closely related to AmpC β-lactamases. AmpH has been associated with PG recycling, although its enzymatic activity remained uncharacterized until now. Construction and purification of His-tagged AmpH from E. coli permitted a detailed study of its enzymatic properties. The N-terminal export signal of AmpH is processed, but the protein remains membrane associated. The PBP nature of AmpH was demonstrated by its ability to bind the β-lactams Bocillin FL (a fluorescent penicillin) and cefmetazole. In vitro assays with AmpH and specific muropeptides demonstrated that AmpH is a bifunctional DD-endopeptidase and DD-carboxypeptidase. Indeed, the enzyme cleaved the cross-linked dimers tetrapentapeptide (D45) and tetratetrapeptide (D44) with efficiencies (k(cat)/K(m)) of 1,200 M(-1) s(-1) and 670 M(-1) s(-1), respectively, and removed the terminal D-alanine from muropeptides with a C-terminal D-Ala-D-Ala dipeptide. Both DD-peptidase activities were inhibited by 40 μM cefmetazole. AmpH also displayed a weak β-lactamase activity for nitrocefin of 1.4 × 10(-3) nmol/μg protein/min, 1/1,000 the rate obtained for AmpC under the same conditions. AmpH was also active on purified sacculi, exhibiting the bifunctional character that was seen with pure muropeptides. The wide substrate spectrum of the DD-peptidase activities associated with AmpH supports a role for this protein in PG remodeling or recycling.

  5. AmpC β-内酰胺酶研究进展

    Institute of Scientific and Technical Information of China (English)

    赵世巧; 夏云; 陈宏础



  6. A Computational Modeling and Simulation Approach to Investigate Mechanisms of Subcellular cAMP Compartmentation. (United States)

    Yang, Pei-Chi; Boras, Britton W; Jeng, Mao-Tsuen; Docken, Steffen S; Lewis, Timothy J; McCulloch, Andrew D; Harvey, Robert D; Clancy, Colleen E


    Subcellular compartmentation of the ubiquitous second messenger cAMP has been widely proposed as a mechanism to explain unique receptor-dependent functional responses. How exactly compartmentation is achieved, however, has remained a mystery for more than 40 years. In this study, we developed computational and mathematical models to represent a subcellular sarcomeric space in a cardiac myocyte with varying detail. We then used these models to predict the contributions of various mechanisms that establish subcellular cAMP microdomains. We used the models to test the hypothesis that phosphodiesterases act as functional barriers to diffusion, creating discrete cAMP signaling domains. We also used the models to predict the effect of a range of experimentally measured diffusion rates on cAMP compartmentation. Finally, we modeled the anatomical structures in a cardiac myocyte diad, to predict the effects of anatomical diffusion barriers on cAMP compartmentation. When we incorporated experimentally informed model parameters to reconstruct an in silico subcellular sarcomeric space with spatially distinct cAMP production sites linked to caveloar domains, the models predict that under realistic conditions phosphodiesterases alone were insufficient to generate significant cAMP gradients. This prediction persisted even when combined with slow cAMP diffusion. When we additionally considered the effects of anatomic barriers to diffusion that are expected in the cardiac myocyte dyadic space, cAMP compartmentation did occur, but only when diffusion was slow. Our model simulations suggest that additional mechanisms likely contribute to cAMP gradients occurring in submicroscopic domains. The difference between the physiological and pathological effects resulting from the production of cAMP may be a function of appropriate compartmentation of cAMP signaling. Therefore, understanding the contribution of factors that are responsible for coordinating the spatial and temporal

  7. Metabolites of an Epac-selective cAMP analog induce cortisol synthesis by adrenocortical cells through a cAMP-independent pathway.

    Directory of Open Access Journals (Sweden)

    Judith A Enyeart

    Full Text Available Adrenal zona fasciculata (AZF cells express a cAMP-activated guanine nucleotide exchange protein (Epac2 that may function in ACTH-stimulated cortisol synthesis. Experiments were done to determine whether cAMP analogs that selectively activate Epacs could induce cortisol synthesis and the expression of genes coding for steroidogenic proteins in bovine AZF cells. Treatment of AZF cells with the Epac-selective cAMP analog (ESCA 8CPT-2'-OMe-cAMP induced large (>100 fold, concentration-dependent, delayed increases in cortisol synthesis and the expression of mRNAs coding for the steroid hydroxylases CYP11a1, CYP17, CYP21, and the steroid acute regulatory protein (StAR. However, a non-hydrolyzable analog of this ESCA, Sp-8CPT-2'-OMe-cAMP, failed to stimulate cortisol production even at concentrations that activated Rap1, a downstream effector of Epac2. Accordingly, putative metabolites of 8CPT-2'-OMe-cAMP, including 8CPT-2'-OMe-5'AMP, 8CPT-2'-OMe-adenosine, and 8CPT-adenine all induced cortisol synthesis and steroid hydroxylase mRNA expression with a temporal pattern, potency, and effectiveness similar to the parent compound. At concentrations that markedly stimulated cortisol production, none of these metabolites significantly activated cAMP-dependent protein kinase (PKA. These results show that one or more metabolites of the ESCA 8CPT-2'-OMe-cAMP induce cortico-steroidogenesis by activating a panel of genes that code for steroidogenic proteins. The remarkable increases in cortisol synthesis observed in this study appear to be mediated by a novel cAMP-, Epac- and PKA-independent signaling pathway.

  8. Effect of cold-ischemia time on nuclear factor-κB activation and inflammatory response in graft after orthotopic liver transplantation in rats

    Institute of Scientific and Technical Information of China (English)

    Xiao-Ping Gu; Yong Jiang; Fu-Tao Xu; Yu-Dong Qiu; Yi-Tao Ding


    AIM: To study the mechanism and effect of nuclear factorκB (NF-κB) activation and inflammatory response on the extended cold-preserved graft injury after orthotopic liver transplantation (OLT).METHODS: OLT was performed in rats with varying time of cold ischemia grafts (6, 18 and 24 h in University Wisconsin solution at 4 ℃). We determined the time of NF-κB activation and expression of tumor necrosisfactor-α (TNF-α), cytokineinducible neutrophil chemoattractant (CINC), and intercellular adhesion molecule-1 (ICAM-1) within 6 h after reperfusion.Serum alarming aminotransferase (ALT), neutrophil sequestration, circulating neutrophil CD11b and L- selectin expression were also evaluated.RESULTS: The accumulation of neutrophils in the graft was significantly increased in the 18 h and 24 h cold-ischemia groups within 0.5 h after reperfusion, compared with the 6 h group. But the strongly activated neutrophils was slightly increased at 2 h after reperfusion and remained at high levels 4 h after reperfusion, which was synchronized with the common situation of recipients after transplantation.Prolonged cold-preservation did not affect neutrophil accumulation and activation. NF-κB activation preceded the expression of TNF-α, CINC, and ICAM-1 in the liver, which was significantly increased with prolonged cold preservation.In prolonged cold preserved grafts, prominently elevated NF-κB activation occurred at 0.5 h and 1 h, compared with that at 2 h after reperfusion, which was consistent with greatly increased intrahepatic TNF-α response.CONCLUSION: NF-κB activation is correlated with the expression of TNF-α, CINC, and ICAM-1 in vivo in OLT rats.Extended cold preservation of grafts might up-regulate TNF-α,CINC, and ICAM-1 expression in the grafts, most probably through elevated NF-κB activation, and might contribute to neutrophil infiltration in the grafts after reperfusion. Elevated NF-κB activity is harmful to inflammatory response in the grafts, and inhibited

  9. Compliance Study of Endovascular Stent Grafts Incorporated with Polyester and Polyurethane Graft Materials in both Stented and Unstented Zones

    Directory of Open Access Journals (Sweden)

    Ying Guan


    Full Text Available Compliance mismatch between stent graft and host artery may induce complications and blood flow disorders. However, few studies have been reported on stent graft compliance. This study aims to explore the deformation and compliance of stent graft in stented and unstented zones under three pressure ranges. Compliance of two stent grafts incorporated with polyurethane graft (nitinol-PU and polyester graft (nitinol-PET materials respectively were tested; the stents used in the two stent grafts were identical. For the circumferential deformation of the stent grafts under each pressure range, the nitinol-PET stent graft was uniform in both zones. The nitinol-PU stent graft was circumferentially uniform in the stented zone, however, it was nonuniform in the unstented zone. The compliance of the PU graft material was 15 times higher than that of the PET graft. No significant difference in compliance was observed between stented and unstented zones of the nitinol-PET stent graft regardless of the applied pressure range. However, for the nitinol-PU stent graft, compliance of the unstented PU region was approximately twice that of the stented region; thus, compliance along the length of the nitinol-PU stent graft was not constant and different from that of the nitinol-PET stent graft.

  10. Enrichment of autologous fat grafts with ex-vivo expanded adipose tissue-derived stem cells for graft survival

    DEFF Research Database (Denmark)

    Kølle, Stig-Frederik Trojahn; Fischer-Nielsen, Anne; Mathiasen, Anders Bruun


    Autologous fat grafting is increasingly used in reconstructive surgery. However, resorption rates ranging from 25% to 80% have been reported. Therefore, methods to increase graft viability are needed. Here, we report the results of a triple-blind, placebo-controlled trial to compare the survival...... of fat grafts enriched with autologous adipose-derived stem cells (ASCs) versus non-enriched fat grafts....

  11. Treatment of gingival recession in two surgical stages: Free gingival graft and connective tissue grafting. (United States)

    Henriques, Paulo Sergio Gomes; Nunes, Marcelo Pereira; Pelegrine, Andre Antonio


    This report describes a clinical case of severe Miller Class II gingival recession treated by two stages of surgery that combined a free gingival graft and connective tissue grafting. First, a free gingival graft (FGG) was performed to obtain an adequate keratinized tissue level. Three months later, a connective tissue graft (CTG) was performed to obtain root coverage. The results indicated that the FGG allows for a gain in the keratinized tissue level and the CTG allows for root coverage with decreased recession level after 16 months. Therefore, for this type of specific gingival recession, the combination of FGG and CTG can be used.

  12. Resolution of severe graft steatosis following dual-graft living donor liver transplantation. (United States)

    Moon, DeokBog; Lee, SungGyu; Hwang, Shin; Kim, KiHun; Ahn, ChulSoo; Park, KwangMin; Ha, TaeYong; Song, GiWon


    Although severely steatotic liver grafts are not suitable for transplantation, they have been used when other, more optimal donors were not available, especially for living donor liver transplantation (LDLT) using two liver grafts. Here we present two cases of dual-graft LDLT in which the recipients showed rapid and complete clearing of fat from livers with previously severe steatosis. In the first case, two left lateral segment grafts were used, one of which was 70% steatotic. Preoperative and posttransplant two-week liver-to-spleen computed tomography-value (L/S) ratios were 0.48 and 1.25, respectively. A liver biopsy taken two weeks after transplantation showed that the fatty changes had almost disappeared. The second case used one left lobe and one left lateral segment graft, the latter of which was 80% steatotic. Preoperative and two-week L/S ratio were 0.58 and 1.34, respectively, and a liver biopsy taken two weeks after transplantation showed less than 3% steatosis. The two donors of the severely steatotic liver grafts recovered uneventfully. These findings show that the fat content of the liver grafts was rapidly removed after transplantation. This observation is helpful in understanding the recovery sequences following transplantation of steatotic liver grafts, as well as expanding the acceptability of steatotic liver grafts.

  13. Polyethylene glycol-grafted polystyrene particles. (United States)

    Meng, Fenghua; Engbers, Gerard H M; Feijen, Jan


    Densely pegylated particles that can serve as a model system for artificial cells were prepared by covalently grafting amino polyethylene glycol (PEG, molecular weight 3400 or 5000) onto carboxyl polystyrene particles (PS-COOH) using carbodiimide chemistry. PEG-modified particles (PS-PEG) were characterized by determination of the PEG surface concentration, zeta-potential, size, and morphology. Under optimized grafting conditions, a dense "brush-like" PEG layer was formed. A PEG surface concentration of approximately 60 pmol/cm2, corresponding with an average distance between grafted PEG chains of approximately 17 A can be realized. It was shown that grafting of PEG onto PS-COOH reduced the adsorption of proteins from human plasma (85 vol %) in phosphate-buffered saline up to 90%.

  14. Fluorescent Bioactive Corrole Grafted-Chitosan Films. (United States)

    Barata, Joana F B; Pinto, Ricardo J B; Vaz Serra, Vanda I R C; Silvestre, Armando J D; Trindade, Tito; Neves, Maria Graça P M S; Cavaleiro, José A S; Daina, Sara; Sadocco, Patrizia; Freire, Carmen S R


    Transparent corrole grafted-chitosan films were prepared by chemical modification of chitosan with a corrole macrocycle, namely, 5,10,15-tris(pentafluorophenyl)corrole (TPFC), followed by solvent casting. The obtained films were characterized in terms of absorption spectra (UV-vis), FLIM (fluorescence lifetime imaging microscopy), structure (FTIR, XPS), thermal stability (TGA), thermomechanical properties (DMA), and antibacterial activity. The results showed that the chemical grafting of chitosan with corrole units did not affect its film-forming ability and that the grafting yield increased with the reaction time. The obtained transparent films presented fluorescence which increases with the amount of grafted corrole units. Additionally, all films showed bacteriostatic effect against S. aureus, as well as good thermomechanical properties and thermal stability. Considering these features, promising applications may be envisaged for these corrole-chitosan films, such as biosensors, bioimaging agents, and bioactive optical devices.

  15. Cyclic AMP enhances TGFβ responses of breast cancer cells by upregulating TGFβ receptor I expression.

    Directory of Open Access Journals (Sweden)

    Ilka Oerlecke

    Full Text Available Cellular functions are regulated by complex networks of many different signaling pathways. The TGFβ and cAMP pathways are of particular importance in tumor progression. We analyzed the cross-talk between these pathways in breast cancer cells in 2D and 3D cultures. We found that cAMP potentiated TGFβ-dependent gene expression by enhancing Smad3 phosphorylation. Higher levels of total Smad3, as observed in 3D-cultured cells, blocked this effect. Two Smad3 regulating proteins, YAP (Yes-associated protein and TβRI (TGFβ receptor 1, were responsive to cAMP. While YAP had little effect on TGFβ-dependent expression and Smad3 phosphorylation, a constitutively active form of TβRI mimicked the cAMP effect on TGFβ signaling. In 3D-cultured cells, which show much higher levels of TβRI and cAMP, TβRI was unresponsive to cAMP. Upregulation of TβRI expression by cAMP was dependent on transcription. A proximal TβRI promoter fragment was moderately, but significantly activated by cAMP suggesting that cAMP increases TβRI expression at least partially by activating TβRI transcription. Neither the cAMP-responsive element binding protein (CREB nor the TβRI-regulating transcription factor Six1 was required for the cAMP effect. An inhibitor of histone deacetylases alone or together with cAMP increased TβRI expression by a similar extent as cAMP alone suggesting that cAMP may exert its effect by interfering with histone acetylation. Along with an additive stimulatory effect of cAMP and TGFβ on p21 expression an additive inhibitory effect of these agents on proliferation was observed. Finally, we show that mesenchymal stem cells that interact with breast cancer cells can simultaneously activate the cAMP and TGFβ pathways. In summary, these data suggest that combined effects of cAMP and TGFβ, as e.g. induced by mesenchymal stem cells, involve the upregulation of TβRI expression on the transcriptional level, likely due to changes in histone acetylation

  16. Prevention of grafted liver from reperfusive injury

    Institute of Scientific and Technical Information of China (English)

    Kai Ma; Yang yu; Xian-Min Bu; Yan-Jun Li; Xian-Wei Dai; Liang Wang; Yang Dai; Hai-Ying Zhao; Xiang-Hong Yang


    @@ INTRODUCTIONThe incidence of primary non-function(PNF)of grafted liver in the early postoperative stage is 2%-23%[1-4],its main cause is the ischemic-rechemic injure[5,6].In this experiment,anisodamine was added into the preserving fluid and the grafted liver was rewarmed at different temperatures to protect the cell membranc and prevent ischemic-reperfusive injury.

  17. Grafting of a LLDPE using gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Catari, E. [Centro de Quimica, Laboratorio de Polimeros Instituto Venezolano de Investigaciones Cientificas (IVIC) (Venezuela); Albano, C. [Centro de Quimica, Laboratorio de Polimeros Instituto Venezolano de Investigaciones Cientificas (IVIC) (Venezuela) and Universidad Central de Venezuela, Facultad de Ingenieria, Escuela de Ingenieria Quimica (Venezuela)]. E-mail:; Karam, A. [Centro de Quimica, Laboratorio de Polimeros Instituto Venezolano de Investigaciones Cientificas (IVIC) (Venezuela)]. E-mail:; Perera, R. [Departamento de Mecanica, Universidad Simon Bolivar (Venezuela); Silva, P. [Centro de Fisica, Laboratorio de Fisica de la Materia Condensada, Instituto Venezolano de Investigaciones Cientificas (IVIC), Caracas (Venezuela); Gonzalez, J. [Departamento de Mecanica, Universidad Simon Bolivar (Venezuela)


    In this investigation, the grafting of a commercial linear low-density polyethylene (LLDPE) with different concentrations of diethyl maleate (DEM, 5 and 15 wt.%) was carried out at different absorbed doses from a cobalt-60 source of gamma rays (0, 15, 30, 50, 100, 200 kGy). This process was performed in a decalin solution at 10% w/v to obtain a homogeneous dispersion of the monomer into the polyethylene matrix. The grafting degree was estimated by means of FTIR using a calibration curve reported in literature. Thermal properties of the functional polymers were studied by thermogravimetric analysis (TGA). Melt flow index (MFI) values were also taken. The results found indicate that the grafting degree increases as the concentration of DEM in the reaction mixture and the absorbed doses are increased upto 100 kGy, as expected. However, the behavior at higher doses is attributed to secondary reactions such as long-chain branching and/or crosslinking, which are faster than radical reactions responsible for the grafting of the DEM onto the polymeric chain. This fact was ascertained by the decrease of the MFI values as the applied irradiation was increased, irrespective of the quantity of DEM used in the grafting reaction. Therefore, in order to obtain a high grafting degree, the absorbed dose should be estimated carefully. Initial degradation temperatures of the grafted PEs decreased when the gamma irradiation dose was higher than 100 kGy. This indicates that the thermal stability decreases as higher doses are applied to the material, which is associated to branching and crosslinking. The grafting degree never exceeded 0.3 mol%, which demonstrates the low efficiency of the functionalization procedure here presented.

  18. DNA nanosensor surface grafting and salt dependence (United States)

    Carvalho, B. G.; Fagundes, J.; Martin, A. A.; Raniero, L.; Favero, P. P.


    In this paper we investigated the Paracoccidoides brasiliensis fungus nanosensor by simulations of simple strand DNA grafting on gold nanoparticle. In order to improve the knowledge of nanoparticle environment, the addiction of salt solution was studied at the models proposed by us. Nanoparticle and DNA are represented by economic models validated by us in this paper. In addition, the DNA grafting and salt influences are evaluated by adsorption and bond energies calculations. This theoretical evaluation gives support to experimental diagnostics techniques of diseases.

  19. Prolonged chewing at lunch decreases later snack intake. (United States)

    Higgs, Suzanne; Jones, Alison


    Prolonged chewing of food can reduce meal intake. However, whether prolonged chewing influences intake at a subsequent eating occasion is unknown. We hypothesised that chewing each mouthful for 30s would reduce afternoon snack intake more than (a) an habitual chewing control condition, and (b) an habitual chewing condition with a pauses in between each mouthful to equate the meal durations. We further hypothesised that this effect may be related to effects of prolonged chewing on lunch memory. Forty three participants ate a fixed lunch of sandwiches in the laboratory. They were randomly allocated to one of the three experimental groups according to a between-subjects design. Appetite, mood and lunch enjoyment ratings were taken before and after lunch and before snacking. Snack intake of candies at a taste test 2h after lunch was measured as well as rated vividness of lunch memory. Participants in the prolonged chewing group ate significantly fewer candies than participants in the habitual chewing group. Snack intake by the pauses group did not differ from either the prolonged or habitual chewing groups. Participants in the prolonged chewing group were less happy and enjoyed their lunch significantly less than participants in other conditions. Appetite ratings were not different across groups. Rated vividness of lunch memory was negatively correlated with intake but there was no correlation with rated lunch enjoyment. Prolonged chewing of a meal can reduce later snack intake and further investigation of this technique for appetite control is warranted.

  20. Polypeptide Grafted Hyaluronan: Synthesis and Characterization

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiaojun [ORNL; Messman, Jamie M [ORNL; Mays, Jimmy [ORNL; Baskaran, Durairaj [University of Tennessee, Knoxville (UTK)


    Poly(L-leucine) grafted hyaluronan (HA-g-PLeu) has been synthesized via a Michael addition reaction between primary amine terminated poly(L-leucine) and acrylate-functionalized HA (TBAHA-acrylate). The precursor hyaluronan was first functionalized with acrylate groups by reaction with acryloyl chloride in the presence of triethylamine in N,N-dimethylformamide. 1H NMR analysis of the resulting product indicated that an increase in the concentration of acryloylchoride with respect to hydroxyl groups on HA has only a moderate effect on functionalization efficiency, f. A precise control of stoichiometry was not achieved, which could be attributed to partial solubility of intermolecular aggregates and the hygroscopic nature of HA. Michael addition at high [PLeu- NH2]/[acrylate]TBAHA ratios gave a molar grafting ratio of only 0.20 with respect to the repeat unit of HA, indicating grafting limitation due to insolubility of the grafted HA-g-PLeu. Soluble HA-g-PLeu graft copolymers were obtained for low grafting ratios (<0.039) with <8.6% by mass of PLeu and were characterized thoroughly using light scattering, 1H NMR, FT-IR, and AFM techniques. Light scattering experiments showed a strong hydrophobic interaction between PLeu chains, resulting in aggregates with segregated nongrafted HA segments. This yields local networks of aggregates, as demonstrated by atomic force microscopy. Circular dichroism spectroscopy showed a -sheet conformation for aggregates of poly(L-leucine).

  1. cAMP biosensors applied in molecular pharmacological studies of G protein-coupled receptors

    DEFF Research Database (Denmark)

    Mathiesen, Jesper Mosolff; Vedel, Line; Bräuner-Osborne, Hans


    end-point assays for quantifying GPCR-mediated changes in intracellular cAMP levels exist. More recently, fluorescence resonance energy transfer (FRET)-based cAMP biosensors that can quantify intracellular cAMP levels in real time have been developed. These FRET-based cAMP biosensors have been used...... primarily in single cell FRET microscopy to monitor and visualize changes in cAMP upon GPCR activation. Here, a similar cAMP biosensor with a more efficient mCerulean/mCitrine FRET pair is described for use in the 384-well plate format. After cloning and expression in HEK293 cells, the biosensor...... is characterized in the 384-well plate format and used for measuring the signaling of the G(s)-coupled ß(2)-adrenergic receptor. The procedures described may be applied for other FRET-based biosensors in terms of characterization and conversion to the 384-well plate format....

  2. Modulation of the cAMP signaling pathway after traumatic brain injury


    Atkins, Coleen M.; Oliva, Anthony A.; Alonso, Ofelia F.; Pearse, Damien D.; Bramlett, Helen M; Dietrich, W. Dalton


    Traumatic brain injury (TBI) results in both focal and diffuse brain pathologies that are exacerbated by the inflammatory response and progress from hours to days after the initial injury. Using a clinically relevant model of TBI, the parasagittal fluid-percussion brain injury (FPI) model, we found injury-induced impairments in the cyclic AMP (cAMP) signaling pathway. Levels of cAMP were depressed in the ipsilateral parietal cortex and hippocampus, as well as activation of its downstream targ...

  3. Rasd1 Modulates the Coactivator Function of NonO in the Cyclic AMP Pathway


    Shufen Angeline Ong; Jen Jen Tan; Wai Loon Tew; Ken-Shiung Chen


    All living organisms exhibit autonomous daily physiological and behavioural rhythms to help them synchronize with the environment. Entrainment of circadian rhythm is achieved via activation of cyclic AMP (cAMP) and mitogen-activated protein kinase signaling pathways. NonO (p54nrb) is a multifunctional protein involved in transcriptional activation of the cAMP pathway and is involved in circadian rhythm control. Rasd1 is a monomeric G protein implicated to play a pivotal role in potentiating b...

  4. Bicarbonate-responsive “soluble” adenylyl cyclase defines a nuclear cAMP microdomain (United States)

    Zippin, Jonathan H.; Farrell, Jeanne; Huron, David; Kamenetsky, Margarita; Hess, Kenneth C.; Fischman, Donald A.; Levin, Lonny R.; Buck, Jochen


    Bicarbonate-responsive “soluble” adenylyl cyclase resides, in part, inside the mammalian cell nucleus where it stimulates the activity of nuclear protein kinase A to phosphorylate the cAMP response element binding protein (CREB). The existence of this complete and functional, nuclear-localized cAMP pathway establishes that cAMP signals in intracellular microdomains and identifies an alternate pathway leading to CREB activation. PMID:14769862

  5. Bicarbonate-responsive “soluble” adenylyl cyclase defines a nuclear cAMP microdomain



    Bicarbonate-responsive “soluble” adenylyl cyclase resides, in part, inside the mammalian cell nucleus where it stimulates the activity of nuclear protein kinase A to phosphorylate the cAMP response element binding protein (CREB). The existence of this complete and functional, nuclear-localized cAMP pathway establishes that cAMP signals in intracellular microdomains and identifies an alternate pathway leading to CREB activation.

  6. Low Voltage CMOS op-amp with Rail-to-Rail Input/Output Swing


    Gopalaiah, SV; Shivaprasad, AP


    As the supply voltage to a standard CMOS op-amp is reduced, the input common mode range and the output swing get reduced drastically. Special biasing circuits have to be used to raise them up to rail-to-rail supply voltage. Three low voltage op-amps with new biasing circuits have been proposed in this paper and their performance evaluated. The op-amp design is focused on dynamic range and high drive capability.

  7. Occurrence and Detection of AmpC β-lactmases and plasmid-mediated ampC among Escherichia coli%大肠埃希菌中AmpC酶和质粒介导的ampC基因的发生和检测

    Institute of Scientific and Technical Information of China (English)

    王锦娜; 邵海枫; 姚兵; 王卫萍; 艾冬琴; 史利宁; 张小卫


    目的从临床分离的大肠埃希菌(E.coli)中检测AmpC酶及质粒介导的ampC基因.方法选择从临床分离的可疑产ESBLs和AmpC 2种酶的40株大肠埃希菌,用NCCLS推荐的微量肉汤稀释法检测耐药表型,三维酶试验检测AmpC酶和ES-BLs,PCR扩增质粒型ampC基因和ESBLs基因,肉汤交配法检测质粒型ampC基因的接合传递性.结果在三维试验中,40株菌中有39株产β-内酰胺酶,其中21株产ESBLs和AmpC 2种酶,15株单产ESBLs,3株单产AmpC酶.在PCR扩增试验中,8株扩增出质粒介导的ampC基因,7株为CIT型,1株为DHA型;34株扩增出blaTEM、blaCTX-M、blaOXA 3型ESBLs基因中的至少1个型,未扩增出blaSHV.8株携带质粒型ampC基因的菌株,共筛选出9株接合子.结论AmpC酶已在我院的大肠埃希菌中出现,由质粒编码的AmpC酶可在细菌间传递.

  8. AmpC beta lactamases among Gram negative clinical isolates from a tertiary hospital, South India


    Parveen R. Mohamudha; Harish, B.N.; Parija, S.C.


    AmpC β-lactamases are cephalosporinases that hydrolyze cephamycins as well as other extended-spectrum cephalosporins and are poorly inhibited by clavulanic acid. Although reported with increasing frequency, the true rate of occurrence of AmpC β-lactamases in different organisms, including members of Enterobacteriaceae, remains unknown. The present study was designed to determine the occurrence of AmpC enzyme-harbouring Gram-negative clinical isolates in a tertiary care hospital in P...

  9. Dynamics of β-adrenergic/cAMP signaling and morphological changes in cultured astrocytes. (United States)

    Vardjan, Nina; Kreft, Marko; Zorec, Robert


    The morphology of astrocytes, likely regulated by cAMP, determines the structural association between astrocytes and the synapse, consequently modulating synaptic function. β-Adrenergic receptors (β-AR), which increase cytosolic cAMP concentration ([cAMP]i ), may affect cell morphology. However, the real-time dynamics of β-AR-mediated cAMP signaling in single live astrocytes and its effect on cell morphology have not been studied. We used the fluorescence resonance energy transfer (FRET)-based cAMP biosensor Epac1-camps to study time-dependent changes in [cAMP]i ; morphological changes in primary rat astrocytes were monitored by real-time confocal microscopy. Stimulation of β-AR by adrenaline, noradrenaline, and isoprenaline, a specific agonist of β-AR, rapidly increased [cAMP]i (∼15 s). The FRET signal response, mediated via β-AR, was faster than in the presence of forskolin (twofold) and dibutyryl-cAMP (>35-fold), which directly activate adenylyl cyclase and Epac1-camps, respectively, likely due to slow entry of these agents into the cytosol. Oscillations in [cAMP]i have not been recorded, indicating that cAMP-dependent processes operate in a slow time domain. Most Epac1-camps expressing astrocytes revealed a morphological change upon β-AR activation and attained a stellate morphology within 1 h. The morphological changes exhibited a bell-shaped dependency on [cAMP]i . The 5-10% decrease in cell cross-sectional area and the 30-50% increase in cell perimeter are likely due to withdrawal of the cytoplasm to the perinuclear region and the appearance of protrusions on the surface of astrocytes. Because astrocyte processes ensheath neurons, β-AR/cAMP-mediated morphological changes can modify the geometry of the extracellular space, affecting synaptic, neuronal, and astrocyte functions in health and disease.

  10. Cultured lymphocytes from alcoholic subjects have altered cAMP signal transduction.


    Nagy, L E; Diamond, I; Gordon, A.


    Previous work has shown that freshly isolated lymphocytes from alcoholic subjects show significantly reduced basal and adenosine receptor-stimulated cAMP levels. This decrease could be due to ethanol-induced cellular adaptation or to a genetic difference in the regulation of cAMP signal transduction. Therefore, we cultured human lymphocytes in defined medium without ethanol for 7-8 days and then examined differences in receptor-dependent cAMP accumulation between lymphocytes from alcoholic an...

  11. Role of cAMP in the reactivation of demembranated ram spermatozoa. (United States)

    San Agustin, J T; Witman, G B


    Ejaculated ram sperm were demembranated with Triton X-100, separated from the detergent-soluble matrix, and reactivated [San Agustin and Witman (1993): Cell Motil. Cytoskeleton 24:264-273]. The percent motility of models prepared from freshly washed sperm was comparable to that of the washed sample before demembranation, regardless of whether cAMP was included in the reactivation medium. However, demembranated models derived from aging or metabolically inhibited sperm exhibited a lower percent reactivation and required cAMP to attain the level of motility of freshly washed sperm. Cyclic AMP was approximately 100 times more effective than cGMP. The requirement for cAMP could be bypassed by addition of porcine heart cAMP-dependent protein kinase (PKA) catalytic subunit to the reactivation medium, demonstrating that cAMP was acting via PKA. The cAMP stimulation of reactivation was not affected by inclusion of the PKA inhibitor PKI(5-24) in the reactivation medium, but was decreased when the models were preincubated with PKI(5-24) prior to reactivation. The cytosol-free models retained > 90% of the sperm PKA activity; therefore, the PKA appears to be anchored to internal sperm structures. This PKA could not be extracted by cAMP or Triton X-100 alone, but only by cAMP and Triton X-100 in combination. We conclude that cAMP-dependent protein phosphorylation is critical for sperm motility, but that the essential protein phosphate sites turn over slowly under our reactivation conditions, so that the cAMP requirement is apparent only in models prepared from sperm having a low internal ATP or cAMP content. Interestingly, reactivation was rapidly blocked by the peptide arg-lys-arg-ala-arg-lys-glu, which has been reported to be a selective inhibitor of cGMP-dependent protein kinase.

  12. Nanomolar Inhibitors of AmpC [beta]-Lactamase

    Energy Technology Data Exchange (ETDEWEB)

    Morandi, Federica; Caselli, Emilia; Morandi, Stefania; Focia, Pamela J.; Blazquez, Jesus; Shoichet, Brian K.; Prati, Fabio (Degali); (NIH); (NWU); (UCSF)


    {beta}-lactamases are the most widespread resistance mechanism to {beta}-lactam antibiotics, such as the penicillins and the cephalosporins. In an effort to combat these enzymes, a combination of stereoselective organic synthesis, enzymology, microbiology, and X-ray crystallography was used to design and evaluate new carboxyphenyl-glycylboronic acid transition-state analogue inhibitors of the class C {beta}-lactamase AmpC. The new compounds improve inhibition by over 2 orders of magnitude compared to analogous glycylboronic acids, with K{sub i} values as low as 1 nM. On the basis of the differential binding of different analogues, the introduced carboxylate alone contributes about 2.1 kcal/mol in affinity. This carboxylate corresponds to the ubiquitous C3(4)' carboxylate of {beta}-lactams, and this energy represents the first thermodynamic measurement of the importance of this group in molecular recognition by class C {beta}-lactamases. The structures of AmpC in complex with two of these inhibitors were determined by X-ray crystallography at 1.72 and 1.83 {angstrom} resolution. These structures suggest a structural basis for the high affinity of the new compounds and provide templates for further design. The highest affinity inhibitor was 5 orders of magnitude more selective for AmpC than for characteristic serine proteases, such as chymotrypsin. This inhibitor reversed the resistance of clinical pathogens to the third generation cephalosporin ceftazidime; it may serve as a lead compound for drug discovery to combat bacterial resistance to {beta}-lactam antibiotics.

  13. An experimental study of postoperative monitoring for innervated free muscle graft by the compound muscle action potential in rabbits. (United States)

    Tan, Soo-Heong; Shigetomi, Mitsunori; Doi, Kazuteru


    This experiment establishes the principles of using the compound muscle action potential (CMAP) as a possible postoperative monitor for free muscle grafts. Twenty rabbits were divided into two groups of ten each to investigate the effects of ischemia on CMAP of the muscles. Rectus femoris model was used and contralateral muscle was used as control. In all muscles total normothermic ischemia of 1.5 hours to mimic the time needed for transfer and inset of the flap was followed by occlusion of the artery in one group and vein in another group after 3 hours. During this ischemia of 1 hour, the CMAP amplitudes decreased and the latencies were prolonged. Latency prolongation was detected within 10 minutes of total, arterial, or venous ischemia. During the revascularization, both amplitude and latency improved, but not to the original values at the start. The results show that CMAP monitoring can provide easily detectable, objective indication of vascular compromise to a muscle graft within as early as 10 minutes of total, arterial, and venous ischemia. Changes in latency are more constant and predictable compared with amplitude changes. This method can provide continuous monitoring and can be used in buried muscle grafts.

  14. Rapid detection of Amp C β-lactamase in Enterobacter cloacae by PCR%基因扩增法快速检测阴沟肠杆菌Amp C β-内酰胺酶

    Institute of Scientific and Technical Information of China (English)

    赵虎; 何铭君; 张时良


    目的:建立检测阴沟肠杆菌Amp C β-内酰胺酶(简称Amp C酶),尤其是持续高产Amp C酶的快速方法.方法:合成阴沟肠杆菌amp C和amp D引物,扩增标准及临床分离的阴沟肠杆菌中amp C和amp D的基因片段,判断待检阴沟肠杆菌是否产Amp C酶,尤其是否产持续高产Amp C酶,并用头孢西丁三维试验加以证实.结果:临床分离的214株阴沟肠杆菌中193株amp C基因扩增阳性,其中amp D扩增阴性者为16株;头孢西丁三维试验阳性18株,其中16株amp C基因扩增阳性而amp D扩增阴性,另有2株amp C和amp D均阳性.去阻遏持续高产型标准菌株amp C扩增阳性、amp D扩增阴性,野生型标准菌株amp C和amp D均扩增阴性.结论:用amp C和amp D引物扩增法可检出18株持续高产Amp C酶的阴沟肠杆菌中的16株,阳性率为88.89%.该方法可用于检测阴沟肠杆菌是否产持续高产Amp C酶.

  15. Design of Low Voltage Low Power CMOS OP-AMP



    Operational amplifiers are an integral part of many analog and mixed signal systems. As the demand for mixed mode integrated circuits increases, the design of analog circuits such as operational amplifiers in CMOS technology becomes more critical. This paper presents a two stage CMOS operational amplifier, which operates at ±1.8V power supply using TSMC 0.18um CMOS technology. The OP-AMP designed exhibit unity gain frequency of 12.6 MHz, and gain of 55.5db with 300uw power dissipa...

  16. Primary adenosine monophosphate (AMP) deaminase deficiency in a hypotonic infant. (United States)

    Castro-Gago, Manuel; Gómez-Lado, Carmen; Pérez-Gay, Laura; Eirís-Puñal, Jesús; Martínez, Elena Pintos; García-Consuegra, Inés; Martín, Miguel Angel


    The spectrum of the adenosine monophosphate (AMP) deaminase deficiency ranges from asymptomatic carriers to patients who manifest exercise-induced muscle pain, occasionally rhabdomyolysis, and idiopathic hyperCKemia. However, previous to the introduction of molecular techniques, rare cases with congenital weakness and hypotonia have also been reported. We report a 6-month-old girl with the association of congenital muscle weakness and hypotonia, muscle deficiency of adenosine monophosphate deaminase, and the homozygous C to T mutation at nucleotide 34 of the adenosine monophosphate deaminase-1 gene. This observation indicates the possible existence of a primary adenosine monophosphate deaminase deficiency manifested by congenital muscle weakness and hypotonia.

  17. Buddhism in Čampā Le Bouddhisme au Champa

    Directory of Open Access Journals (Sweden)

    Anne-Valérie Schweyer


    Full Text Available Čampā is a Far East country, whose Māhāyana Buddhism is known from 7th to 14th century. In fact, Sanskrit and Cam Inscriptions mostly attested Tantric practices, belonging to the Vajrāyana Buddhism, mixing Śaiva and Buddhist believes. More precisely, side by side Śiva and the three Buddha’ emanations, Śākyamuni, Amitābha and Vairocana, are honoured in Čampā, alone with the Goddess Prajñāpāramitā, the true substance of the Doctrine, and, secondary, with Vajrapāni, Lokeśvara and Vajrasattva. The confrontation of the epigraphic testimonies with the archaeological remains is very useful to understand the Buddhism of Čampā, crossroads of trade roads between India and China. Therefore, epigraphic and artistic evidences are used to propose a chronological presentation, with a special development on the revival of the 10th century, and especially, the esoteric way.Le Čampā, pays du centre Vietnam, connut un bouddhisme Māhāyana du xe au xive siècle. Les inscriptions en sanskrit et en cam montrent que ce bouddhisme était essentiellement tantrique, relevant du bouddhisme Vajrāyana, mêlant pratiques Śivaïtes et bouddhiques. Plus précisément, le bouddhisme cam montre qu’aux côtés de Śiva sont honorées les trois émanations du Bouddha, Śākyamuni, Amitābha et Vairocana, avec la déesse Prajñāpāramitā, la Vraie Substance de la Connaissance ; on trouve également Vajrapāni, Lokeśvara et Vajrasattva. La confrontation des témoignages épigraphiques et archéologiques permet de mieux appréhender le bouddhisme cam, à la croisée des routes commerciales entre l’Inde et la Chine. Cet article exploite ces témoignages dans une perspective chronologique, avec un développement particulier pour le Bouddhisme ésotérique au xe siècle.

  18. Shunt for bypass graft of the cavernous carotid artery: an anatomical and technical study. (United States)

    al-Mefty, O; Khalil, N; Elwany, M N; Smith, R R


    During direct surgery of neoplastic and vascular lesions of the cavernous sinus, the intracavernous carotid artery may be injured beyond repair, or its total isolation may be necessary for surgical management of these lesions. The newly developed procedure of a saphenous vein graft bypass of the cavernous carotid artery allows re-establishment of carotid circulation. Patients with poor collateral circulation are at high risk for ischemic complications induced by the prolonged temporary occlusion required to perform the bypass graft. Optimal management of these patients is to perform the venous bypass graft for permanent vascularization while maintaining carotid cerebral circulation through an intraoperative shunt. We studied this procedure in cadavers, and three shunt types were evaluated: the external intrapetrous-supraclinoid shunt (Type A), the internal intrapetrous-supraclinoid shunt (Type B), and the neck internal carotid-supraclinoid shunt (Type C). Anatomical landmarks, techniques, distances, caliber, and materials used are presented. The rationale and candidates for such a procedure are discussed. The specifications of an optimal balloon shunt are presented, and the three procedures are compared.

  19. Intraoperative perfusion contrast echocardiography. Initial experience during coronary artery bypass grafting. (United States)

    Kabas, J S; Kisslo, J; Flick, C L; Johnson, S H; Craig, D M; Stanley, T E; Smith, P K


    Intraoperative evaluation of the effectiveness of myocardial revascularization has been limited by an inability to assess regional myocardial perfusion. Microbubbles of sonicated diatrizoate sodium and diatrizoate meglumine (Renografin) have been an effective echocardiographic contrast agent and have been employed clinically during cardiac catheterization. This recent development in contrast-enhanced two-dimensional echocardiography permits real-time imaging of transmural myocardial blood flow but has not been evaluated in the operating room. This study represents the initial surgical application of this directed technique and was designed to evaluate the safety and efficacy of intraoperative perfusion contrast echocardiography in assessing the results of coronary artery bypass grafting. Twenty men with significant coronary artery disease ranging in age from 49 to 73 years were studied. Direct contrast agent injection into completed saphenous vein bypass grafts caused the myocardium supplied by each graft to be well delineated and provided a tomographic view of contrast distribution. The enhanced region was well correlated with the size and distribution of the native vessel. Rapid contrast washout (less than 20 seconds) indicated satisfactory regional perfusion. Contrast echocardiography prolonged the operation less than 10 minutes and did not result in any perioperative complications.

  20. ACL Revision in Synthetic ACL graft failure (United States)

    Etcheto, H. Rivarola; Zordán, J.; Escobar, G.; Collazo, C.; Palanconi, M.; Autorino, C.; Salinas, E. Alvarez


    The development of synthetic grafts as an alternative to biological grafts for reconstruction of the anterior cruciate ligament dates from 1980. The interest is awakened due to the potential advantages of: The absence of morbidity associated with donor site, and early return to sport. However, this surgical technique has had multiple complications associated with graft: mechanical failures (synthetic graft failure, loss of fixation), synovial foreign body reaction, recurrent stroke, recurrent instability and ultimately, early osteoarthritis. Objectives: We describe the synthetic graft failure LCA, intraoperative findings and details of surgical technique. Methods: Patient 35 years old, with a history of ACL reconstruction four years of evolution in another health center, consultation with the Service knee arthroscopy for acute knee pain left knee during secondary sporting event to a rotation mechanism with fixed foot. On physical examination, presents and positive Lachman maneuver Pivot. Radiografia in a widening of the tibial tunnel is observed. NMR shows a discontinuity of fibers of synthetic graft. Results: First time arthroscopic revision where synthetic plastic LCA identifies with Disruption fiber pattern. Intraoperatively, hypertrophic chronic synovitis localized predominantly in intercóndilo is observed. debridement thereof is performed, and proceeds to the extraction of the synthetic ligament. Then he was made prior cruentado and revival of the edges of the tunnel, filling them with non-irradiated structural bone allograft. At four months as planned and after confirmation by studies incorporating bone graft was performed the second time with the new plastic ACL. It was planned like a primary graft surgery with autologous hamstring prepared in fourfold form, and fixation with modified transtibial technique Biotransfix system proximal and distal screw Biocomposite (arthrex®). A quadruple graft 9 mm was obtained, making good positioning of tunnels and stable

  1. Structural basis for cAMP-mediated allosteric control of the catabolite activator protein. (United States)

    Popovych, Nataliya; Tzeng, Shiou-Ru; Tonelli, Marco; Ebright, Richard H; Kalodimos, Charalampos G


    The cAMP-mediated allosteric transition in the catabolite activator protein (CAP; also known as the cAMP receptor protein, CRP) is a textbook example of modulation of DNA-binding activity by small-molecule binding. Here we report the structure of CAP in the absence of cAMP, which, together with structures of CAP in the presence of cAMP, defines atomic details of the cAMP-mediated allosteric transition. The structural changes, and their relationship to cAMP binding and DNA binding, are remarkably clear and simple. Binding of cAMP results in a coil-to-helix transition that extends the coiled-coil dimerization interface of CAP by 3 turns of helix and concomitantly causes rotation, by approximately 60 degrees , and translation, by approximately 7 A, of the DNA-binding domains (DBDs) of CAP, positioning the recognition helices in the DBDs in the correct orientation to interact with DNA. The allosteric transition is stabilized further by expulsion of an aromatic residue from the cAMP-binding pocket upon cAMP binding. The results define the structural mechanisms that underlie allosteric control of this prototypic transcriptional regulatory factor and provide an illustrative example of how effector-mediated structural changes can control the activity of regulatory proteins.

  2. TSH-induced cyclic AMP production in an ovine thyroid cell line: OVNIS 5H. (United States)

    Fayet, G; Aouani, A; Hovsépian, S


    The TSH-induced cyclic AMP response was studied using a 3-year-old ovine thyroid cell line TSH-independent for growth: OVNIS 5H. The kinetics of cyclic AMP production was followed both in cell layers and in cell culture media, with or without phosphodiesterase inhibitor. It is noteworthy that following the first wave in cyclic AMP obtained within minutes, we observed later a sustained exponential increase in cyclic AMP during the 5 days following TSH stimulation. A bioassay of TSH was derived allowing measurement of 1 microU/ml TSH from a crude bTSH preparation.

  3. AMP-guided tumour-specific nanoparticle delivery via adenosine A1 receptor. (United States)

    Dai, Tongcheng; Li, Na; Han, Fajun; Zhang, Hua; Zhang, Yuanxing; Liu, Qin


    Active targeting-ligands have been increasingly used to functionalize nanoparticles for tumour-specific clinical applications. Here we utilize nucleotide adenosine 5'-monophosphate (AMP) as a novel ligand to functionalize polymer-based fluorescent nanoparticles (NPs) for tumour-targeted imaging. We demonstrate that AMP-conjugated NPs (NPs-AMP) efficiently bind to and are following internalized into colon cancer cell CW-2 and breast cancer cell MDA-MB-468 in vitro. RNA interference and inhibitor assays reveal that the targeting effects mainly rely on the specific binding of AMP to adenosine A1 receptor (A1R), which is greatly up-regulated in cancer cells than in matched normal cells. More importantly, NPs-AMP specifically accumulate in the tumour site of colon and breast tumour xenografts and are further internalized into the tumour cells in vivo via tail vein injection, confirming that the high in vitro specificity of AMP can be successfully translated into the in vivo efficacy. Furthermore, NPs-AMP exhibit an active tumour-targeting behaviour in various colon and breast cancer cells, which is positively related to the up-regulation level of A1R in cancer cells, suggesting that AMP potentially suits for more extensive A1R-overexpressing cancer models. This work establishes AMP to be a novel tumour-targeting ligand and provides a promising strategy for future diagnostic or therapeutic applications.

  4. Coronary vasodilatory, spasmolytic and cAMP-phosphodiesterase inhibitory properties of dihydropyranocoumarins and dihydrofuranocoumarins

    DEFF Research Database (Denmark)

    Thastrup, Ole; Fjalland, B; Lemmich, J


    Twenty-three dihydropyrano- and dihydrofuranocoumarins, most of plant origin, were examined for their effects on the coronary flow of isolated perfused guinea-pig heart, on the Ba2+-induced spasms in isolated guinea-pig ileum, on the cAMP level in guinea-pig heart homogenate and on the cAMP metab...... between the coronary vasodilatory and the cAMP-phosphodiesterase inhibitory activity. The results indicate involvement of cAMP-phosphodiesterase inhibition in coronary vasodilatory effects of acyloxydihydropyrano- and acyloxydihydrofurano-coumarins....

  5. cAMP diffusion in Dictyostelium discoideum: A Green's function method (United States)

    Calovi, Daniel S.; Brunnet, Leonardo G.; de Almeida, Rita M. C.


    A Green’s function method is developed to approach the spatiotemporal equations describing the cAMP production in Dictyostelium discoideum, markedly reducing numerical calculations times: cAMP concentrations and gradients are calculated just at the amoeba locations. A single set of parameters is capable of reproducing the different observed behaviors, from cAMP synchronization, spiral waves and reaction-diffusion patterns to streaming and mound formation. After aggregation, the emergence of a circular motion of amoebas, breaking the radial cAMP field symmetry, is observed.

  6. NMR studies of the AMP-binding site and mechanism of adenylate kinase

    Energy Technology Data Exchange (ETDEWEB)

    Fry, D.C.; Kuby, S.A.; Mildvan, A.S.


    NMR has previously been used to determine the conformation of enzyme-bound MgATP and to locate the MgATP-binding site on adenylate kinase. To determine the conformation and location of the other substrate, AMP, distances have been measured from Cr/sup 3 +/AMPPCP, a linear competitive inhibitor with respect to MgATP, to six protons and to the phosphorus atom of AMP on adenylate kinase, with the paramagnetic probe-T/sub 1/ method. Time-dependent nuclear Overhauser effects (NOEs) have been used to measure five interproton distances on enzyme-bound AMP. These distances were used to determine the conformation of bound AMP in addition to its position with respect to metal-ATP. Ten intermolecular NOEs, from protons of the enzyme to those of AMP, were detected, indicating the proximity of at least three hydrophobic amino acids to bound AMP. These constraints, together with the conformation of AMP and the intersubstrate distances, were used to position AMP into the X-ray structure of adenylate kinase. The AMP binding site is found to be near Leu-116, Arg-171, Val-173, Val-182, and Leu-190; all of these residues have been found to be invariant in muscle-type rabbit, calf, human, porcine.

  7. Impact of bone graft harvesting techniques on bone formation and graft resorption

    DEFF Research Database (Denmark)

    Saulacic, Nikola; Bosshardt, Dieter D; Jensen, Simon S;


    formation and graft resorption in vivo. MATERIAL AND METHODS: Four harvesting techniques were used: (i) corticocancellous blocks particulated by a bone mill; (ii) bone scraper; (iii) piezosurgery; and (iv) bone slurry collected from a filter device upon drilling. The grafts were placed into bone defects...

  8. Supplementation of Ascorbic Acid in Weanling Horses Following Prolonged Transportation

    Directory of Open Access Journals (Sweden)

    Michelle Stives


    Full Text Available Though horses synthesize ascorbic acid in their liver in amounts that meet their needs under normal circumstances, prolonged stress results in low plasma concentrations due to enhanced utilization and renal excretion and can reduce immune function. It was hypothesized that plasma ascorbic acid could be maintained in weanling horses by oral supplementation following prolonged transportation. Weanlings were supplemented with no ascorbic acid (Tx 0: n = 4, 5 grams ascorbic acid twice daily for 5 days (Tx 1: n = 4 or for 10 days (Tx 2: n = 4 following >50 hours of transportation. Supplementation caused slight (P < 0.2 increases in plasma ascorbic acid concentrations. Both supplemented groups had decreased (P < 0.05 plasma concentrations for 1 to 3 weeks following cessation of supplementation, possibly due to increased renal excretion or suppressed hepatic synthesis. Supplementation of ascorbic acid following prolonged stress will increase plasma concentrations, but prolonged supplementation should be avoided.

  9. Physical properties of agave cellulose graft polymethyl methacrylate

    Energy Technology Data Exchange (ETDEWEB)

    Rosli, Noor Afizah; Ahmad, Ishak; Abdullah, Ibrahim; Anuar, Farah Hannan [Polymer Research Centre (PORCE), School of Chemical Sciences and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi Selangor (Malaysia)


    The grafting polymerization of methyl methacrylate and Agave cellulose was prepared and their structural analysis and morphology were investigated. The grafting reaction was carried out in an aqueous medium using ceric ammonium nitrate as an initiator. The structural analysis of the graft copolymers was carried out by Fourier transform infrared and X-ray diffraction. The graft copolymers were also characterized by field emission scanning electron microscopy (FESEM). An additional peak at 1732 cm{sup −1} which was attributed to the C=O of ester stretching vibration of poly(methyl methacrylate), appeared in the spectrum of grafted Agave cellulose. A slight decrease of crystallinity index upon grafting was found from 0.74 to 0.68 for cellulose and grafted Agave cellulose, respectively. Another evidence of grafting showed in the FESEM observation, where the surface of the grafted cellulose was found to be roughed than the raw one.

  10. Physical properties of agave cellulose graft polymethyl methacrylate (United States)

    Rosli, Noor Afizah; Ahmad, Ishak; Abdullah, Ibrahim; Anuar, Farah Hannan


    The grafting polymerization of methyl methacrylate and Agave cellulose was prepared and their structural analysis and morphology were investigated. The grafting reaction was carried out in an aqueous medium using ceric ammonium nitrate as an initiator. The structural analysis of the graft copolymers was carried out by Fourier transform infrared and X-ray diffraction. The graft copolymers were also characterized by field emission scanning electron microscopy (FESEM). An additional peak at 1732 cm-1 which was attributed to the C=O of ester stretching vibration of poly(methyl methacrylate), appeared in the spectrum of grafted Agave cellulose. A slight decrease of crystallinity index upon grafting was found from 0.74 to 0.68 for cellulose and grafted Agave cellulose, respectively. Another evidence of grafting showed in the FESEM observation, where the surface of the grafted cellulose was found to be roughed than the raw one.

  11. Prolongation structure of the Landau–Lifshitz equation

    NARCIS (Netherlands)

    Roelofs, G.H.M.; Martini, R.


    The prolongation method of Wahlquist and Estabrook is applied to the Landau–Lifshitz equation. The resulting prolongation algebra is shown to be isomorphic to a subalgebra of the tensor product of the Lie algebra so(3) with the elliptic curve v α 2−v β 2=j β−j α (α,β=1,2,3), which is essentially a s

  12. Outcome of Induction of Labour in Prolonged Pregnancy. (United States)

    Nasrin, S; Islam, S; Shahida, S M; Begum, R A; Haque, N


    This was a hospital based prospective clinical study conducted among women having prolonged pregnancy to assess the outcome of induction of labour in prolonged pregnancy cases. One hundred and thirty nine women having uncomplicated prolonged pregnancy were studied. The study was carried out in Sir Salimullah Medical College & Mitford Hospital, Dhaka from 01 July 2010 to 30 March 2011. In this study 66% of the respondents had vaginal delivery on routine induction of labour and in 34% cases induction failed. Ninety three percent (93%) of the multigravida had vaginal delivery and in primigravida their vaginal delivery rate was 47.5%. Regarding cervical condition for delivery, 75% of the respondents having favourable cervix had vaginal delivery and in case of unfavourable cervix respondents, they had 55% cases of vaginal delivery. About the foetal outcome it was evidenced from this study that the perinatal adverse outcome increases with the increasing age of gestation beyond 40 completed weeks of gestation. This study showed that the use of prostaglandins for cervical ripening and by confirming the diagnosis of prolonged pregnancy, the delivery outcome in prolonged pregnancy can be improved. The study also showed that induction of labour is not associated with any major complications and the routine induction of labour in prolonged pregnancy is beneficial for both mother and the baby.

  13. Diagnosis, antenatal surveillance and management of prolonged pregnancy: current perspectives. (United States)

    Vitale, S G; Marilli, I; Rapisarda, A M; Iapichino, V; Stancanelli, F; Cianci, A


    Prolonged pregnancy is defined as a pregnancy that extends beyond 42 weeks of gestation (294 days) from the first day of the last normal menstrual period. An accurate estimation of the 'natural' incidence of prolonged pregnancy would require meticulous early pregnancy dating. The use of ultrasound to establish gestational age reduces the number of pregnancies that are classified as prolonged. Prolonged pregnancy is associated with an increased perinatal mortality and morbidity in pregnancies which appear to be otherwise low risk. Postterm births are easily preventable by intervening to deliver with the use of induction of labor. Thus, this potentially problematic condition deserves further attention and careful consideration. The focus of this article is to review and challenge some current concepts surrounding the diagnosis and management of prolonged pregnancy. We outline how to identify those women with prolonged pregnancy and which is the appropriate moment to start monitoring the fetal wellbeing. Finally we address the question of benefits and hazards of induction of labor strategies.

  14. Acute graft versus host disease

    Directory of Open Access Journals (Sweden)

    Vogelsang Georgia B


    Full Text Available Abstract Acute graft-versus-host disease (GVHD occurs after allogeneic hematopoietic stem cell transplant and is a reaction of donor immune cells against host tissues. Activated donor T cells damage host epithelial cells after an inflammatory cascade that begins with the preparative regimen. About 35%–50% of hematopoietic stem cell transplant (HSCT recipients will develop acute GVHD. The exact risk is dependent on the stem cell source, age of the patient, conditioning, and GVHD prophylaxis used. Given the number of transplants performed, we can expect about 5500 patients/year to develop acute GVHD. Patients can have involvement of three organs: skin (rash/dermatitis, liver (hepatitis/jaundice, and gastrointestinal tract (abdominal pain/diarrhea. One or more organs may be involved. GVHD is a clinical diagnosis that may be supported with appropriate biopsies. The reason to pursue a tissue biopsy is to help differentiate from other diagnoses which may mimic GVHD, such as viral infection (hepatitis, colitis or drug reaction (causing skin rash. Acute GVHD is staged and graded (grade 0-IV by the number and extent of organ involvement. Patients with grade III/IV acute GVHD tend to have a poor outcome. Generally the patient is treated by optimizing their immunosuppression and adding methylprednisolone. About 50% of patients will have a solid response to methylprednisolone. If patients progress after 3 days or are not improved after 7 days, they will get salvage (second-line immunosuppressive therapy for which there is currently no standard-of-care. Well-organized clinical trials are imperative to better define second-line therapies for this disease. Additional management issues are attention to wound infections in skin GVHD and fluid/nutrition management in gastrointestinal GVHD. About 50% of patients with acute GVHD will eventually have manifestations of chronic GVHD.

  15. AMPS/AAM凝胶响应性能的研究%Study on response performance of AMPS/AAM hydrogels

    Institute of Scientific and Technical Information of China (English)

    冯霞; 陈莉; 周军杰



  16. Role of 99mTc-labeled disida scan in the assessment of marginal liver grafts after orthotopic transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Karademir, S.; Jurim, O.; Bussuttil, R.W.; Shaked, A. (Department of Surgery, University of California at Los Angeles, Los Angeles, CA (United States)); Csete, M.E. (Department of Anesthesiology, University of California at Los Angeles, Los Angeles, CA (United States)); Finstad, T.; Hawkins, R. (Department of Nuclear Medicine, University of California at Los Angeles, Los Angeles, Ca (United States))


    Accurate prognostic indicators are lacking for livers with early marginal graft function, making the decision to re-transplant a difficult one. Therefore, we studied 99mTc-labeled DISIDA scanning as a predictor of recovery of marginal grafts. Records of 28 liver transplant recipients with prolonged periods of marginal graft function after liver transplantation were analyzed. Twelve of 28 (Group I) had delayed PNF and were re-transplanted within 3-8 days (mean 5.3) of surgery. The remaining 16 (Group II) recovered slowly, with normal graft function at 1 month. All patients received DISIDA scans 2 to 5 d after surgery. Clearance of tracer from the blood pool was slower in Group I patients (77S [+-] 241 sec) than in Group II (260 [+-] 38 sec; p<0.01). Qualitative differences in the pattern of parenchymal uptake were also noted. Homogenous uptake, consistent with cholestasis, was seen in 15/16 (94%) Group II patients, with improved uptake after 7-35 d. In contrast, 11/12 Group I patients had nonhomogenous uptake, consistent with multiple liver infarctions. This pattern correlated with higher peak SGOT in Group I (4358 [+-] 658 U/dl vs. 1636 [+-] 127 U/dl p<0.01), and PT (20 [+-] 0.7 sec vs. 16.5 [+-] 0.36 sec; p<0.01). In summary, delays in DISIDA tracer clearance from blood, and non-homogenous hepatic uptake correlate with elevated liver function tests and with delayed PNF. Homogenous uptake correlates with graft recovery. DISIDA scans may, therefore, be useful in predicting recovery of marginal grafted livers. (au) (17 refs.).

  17. Cyclic GMP-AMP displays mucosal adjuvant activity in mice.

    Directory of Open Access Journals (Sweden)

    Ivana Škrnjug

    Full Text Available The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice. A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity--a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. We further characterize the innate immune stimulation activity in vitro on murine bone marrow-derived dendritic cells and human dendritic cells. The observed results suggest the consideration of cGAMP as a candidate mucosal adjuvant for human vaccines.

  18. Design, synthesis, and initial evaluation of D-glyceraldehyde crosslinked gelatin-hydroxyapatite as a potential bone graft substitute material (United States)

    Florschutz, Anthony Vatroslav

    Utilization of bone grafts for the treatment of skeletal pathology is a common practice in orthopaedic, craniomaxillofacial, dental, and plastic surgery. Autogenous bone graft is the established archetype but has disadvantages including donor site morbidity, limited supply, and prolonging operative time. In order to avoid these and other issues, bone graft substitute materials are becoming increasingly prevalent among surgeons for reconstructing skeletal defects and arthrodesis applications. Bone graft substitutes are biomaterials, biologics, and guided tissue/bone regenerative devices that can be used alone or in combinations as supplements or alternatives to autogenous bone graft. There is a growing interest and trend to specialize graft substitutes for specific indications and although there is good rationale for this indication-specific approach, the development and utility of a more universal bone graft substitute may provide a better answer for patients and surgeons. The aim of the present research focuses on the design, synthesis, and initial evaluation of D-glyceraldehyde crosslinked gelatin-hydroxyapatite composites for potential use as a bone graft substitutes. After initial establishment of rational material design, gelatinhydroxyapatite scaffolds were fabricated with different gelatin:hydroxyapatite ratios and crosslinking concentrations. The synthesized scaffolds were subsequently evaluated on the basis of their swelling behavior, porosity, density, percent composition, mechanical properties, and morphology and further assessed with respect to cell-biomaterial interaction and biomineralization in vitro. Although none of the materials achieved mechanical properties suitable for structural graft applications, a reproducible material design and synthesis was achieved with properties recognized to facilitate bone formation. Select scaffold formulations as well as a subset of scaffolds loaded with recombinant human bone morphogenetic protein-2 were

  19. Occurrence and detection of AmpC β-lactamases among Enterobacteriaceae isolates from patients at Ain Shams University Hospital


    Soha A. El-Hady; Lamiaa A. Adel


    Background: AmpC β-lactamases are often plasmid mediated that hydrolyze all β-lactam antibiotics except cefepime and carbapenems. Aim of the study: We aimed to evaluate the presence of AmpC β-lactamase among Enterobacteriaceae isolates separated from patients with nosocomial infections, and to detect the genetic basis for AmpC production in these strains. Subjects and methods: 50 AmpC β-lactamase Enterobacteriaceae were analyzed for the presence of AmpC production. Three phenotypic AmpC...

  20. 临床常见产AmpC β-内酰胺酶菌株中染色质ampC共同序列的研究%Exploration of the consensus sequence among the genomic ampC from the clinical isolates producing AmpC beta-lactamase

    Institute of Scientific and Technical Information of China (English)

    赵虎; 王寅; 涂婉; 方毅; 庞立峰


    目的 分析临床常见AmpC β-内酰胺酶(简称AmpC酶)产酶菌株中染色质ampC的基因序列,从而为AmpC酶的分子生物学检测以及其调控机制研究提供理论依据.方法 57株临床常见AmpC酶产酶菌株分离自医院感染患者样本,抽提细菌染色质DNA,聚合酶链反应(PCR)扩增ampC基因并连接入pMD19-T载体,双链测序后比对同种细菌之间和不同种细菌之间染色质ampC基因的同源性和共同序列.根据共同序列设计引物,进一步利用该引物检测染色质ampC.结果 57株细菌的基因组中,使用PCR扩增出染色质ampC基因41株,并成功测定了其ampC基因的序列.比对后发现大肠埃希菌、阴沟肠杆菌、鲍曼不动杆菌和产气肠杆菌的染色质ampC菌种内有很高的同源性,但细菌之间的同源性较低.根据共同序列设计出菌种特异性PCR引物,能够有效的鉴定出染色质ampC基因.结论 大肠埃希菌、阴沟肠杆菌、鲍曼不动杆菌和产气肠杆菌各自染色质ampC具有高度同源性,其菌种特异性的ampC引物可用来检测其染色质ampC的存在.

  1. cAMP signaling prevents podocyte apoptosis via activation of protein kinase A and mitochondrial fusion.

    Directory of Open Access Journals (Sweden)

    Xiaoying Li

    Full Text Available Our previous in vitro studies suggested that cyclic AMP (cAMP signaling prevents adriamycin (ADR and puromycin aminonucleoside (PAN-induced apoptosis in podocytes. As cAMP is an important second messenger and plays a key role in cell proliferation, differentiation and cytoskeleton formation via protein kinase A (PKA or exchange protein directly activated by cAMP (Epac pathways, we sought to determine the role of PKA or Epac signaling in cAMP-mediated protection of podocytes. In the ADR nephrosis model, we found that forskolin, a selective activator of adenylate cyclase, attenuated albuminuria and improved the expression of podocyte marker WT-1. When podocytes were treated with pCPT-cAMP (a selective cAMP/PKA activator, PKA activation was increased in a time-dependent manner and prevented PAN-induced podocyte loss and caspase 3 activation, as well as a reduction in mitochondrial membrane potential. We found that PAN and ADR resulted in a decrease in Mfn1 expression and mitochondrial fission in podocytes. pCPT-cAMP restored Mfn1 expression in puromycin or ADR-treated podocytes and induced Drp1 phosphorylation, as well as mitochondrial fusion. Treating podocytes with arachidonic acid resulted in mitochondrial fission, podocyte loss and cleaved caspase 3 production. Arachidonic acid abolished the protective effects of pCPT-cAMP on PAN-treated podocytes. Mdivi, a mitochondrial division inhibitor, prevented PAN-induced cleaved caspase 3 production in podocytes. We conclude that activation of cAMP alleviated murine podocyte caused by ADR. PKA signaling resulted in mitochondrial fusion in podocytes, which at least partially mediated the effects of cAMP.

  2. cAMP signaling prevents podocyte apoptosis via activation of protein kinase A and mitochondrial fusion. (United States)

    Li, Xiaoying; Tao, Hua; Xie, Kewei; Ni, Zhaohui; Yan, Yucheng; Wei, Kai; Chuang, Peter Y; He, John Cijiang; Gu, Leyi


    Our previous in vitro studies suggested that cyclic AMP (cAMP) signaling prevents adriamycin (ADR) and puromycin aminonucleoside (PAN)-induced apoptosis in podocytes. As cAMP is an important second messenger and plays a key role in cell proliferation, differentiation and cytoskeleton formation via protein kinase A (PKA) or exchange protein directly activated by cAMP (Epac) pathways, we sought to determine the role of PKA or Epac signaling in cAMP-mediated protection of podocytes. In the ADR nephrosis model, we found that forskolin, a selective activator of adenylate cyclase, attenuated albuminuria and improved the expression of podocyte marker WT-1. When podocytes were treated with pCPT-cAMP (a selective cAMP/PKA activator), PKA activation was increased in a time-dependent manner and prevented PAN-induced podocyte loss and caspase 3 activation, as well as a reduction in mitochondrial membrane potential. We found that PAN and ADR resulted in a decrease in Mfn1 expression and mitochondrial fission in podocytes. pCPT-cAMP restored Mfn1 expression in puromycin or ADR-treated podocytes and induced Drp1 phosphorylation, as well as mitochondrial fusion. Treating podocytes with arachidonic acid resulted in mitochondrial fission, podocyte loss and cleaved caspase 3 production. Arachidonic acid abolished the protective effects of pCPT-cAMP on PAN-treated podocytes. Mdivi, a mitochondrial division inhibitor, prevented PAN-induced cleaved caspase 3 production in podocytes. We conclude that activation of cAMP alleviated murine podocyte caused by ADR. PKA signaling resulted in mitochondrial fusion in podocytes, which at least partially mediated the effects of cAMP.

  3. Genetically-encoded tools for cAMP probing and modulation in living systems.

    Directory of Open Access Journals (Sweden)

    Valeriy M Paramonov


    Full Text Available Intracellular 3'-5'-cyclic adenosine monophosphate (cAMP is one of the principal second messengers downstream of a manifold of signal transduction pathways, including the ones triggered by G protein-coupled receptors. Not surprisingly, biochemical assays for cAMP have been instrumental for basic research and drug discovery for decades, providing insights into cellular physiology and guiding pharmaceutical industry. However, despite impressive track record, the majority of conventional biochemical tools for cAMP probing share the same fundamental shortcoming - all the measurements require sample disruption for cAMP liberation. This common bottleneck, together with inherently low spatial resolution of measurements (as cAMP is typically analyzed in lysates of thousands of cells, underpin the ensuing limitations of the conventional cAMP assays: 1 genuine kinetic measurements of cAMP levels over time in a single given sample are unfeasible; 2 inability to obtain precise information on cAMP spatial distribution and transfer at subcellular levels, let alone the attempts to pinpoint dynamic interactions of cAMP and its effectors. At the same time, tremendous progress in synthetic biology over the recent years culminated in drastic refinement of our toolbox, allowing us not only to bypass the limitations of conventional assays, but to put intracellular cAMP life-span under tight control – something, that seemed scarcely attainable before. In this review article we discuss the main classes of modern genetically-encoded tools tailored for cAMP probing and modulation in living systems. We examine the capabilities and weaknesses of these different tools in the context of their operational characteristics and applicability to various experimental set-ups involving living cells, providing the guidance for rational selection of the best tools for particular needs.

  4. Vascularized tail bone grafts in rats. (United States)

    Sempuku, T; Tamai, S; Mizumoto, S; Yajima, H


    A new experimental model for vascularized corticocancellous bone grafts was established by investigation of vascular anatomy of the tail in 15 adult Fischer 344 rats and determination of the viability of vascularized tail bone grafts into the abdominal wall in 22 7-week-old rats. The tail bones of 40 rats were then raised on the pedicle of the caudal artery and its venae comitantes, transferred to a resected portion in the femur, and observed for 16 weeks. The vascularized graft showed marked reactive periosteal bone formation during the first and second weeks following transfer, and thereafter, the graft continued to show active bone formation. In transverse section, the sharp processes became rounded. In the cancellous bone, both bone resorption and bone formation were noticeably activated early after transfer, although resorption predominated and the amount of the cancellous bone consequently diminished. The nonvascularized grafts showed "creeping substitution." The results suggest that morphologic adaptation occurs if living (i.e., vascularized) tail bones are transferred to long-bone femurs.

  5. Aortic reconstruction with bovine pericardial grafts

    Directory of Open Access Journals (Sweden)

    Silveira Lindemberg Mota


    Full Text Available INTRODUCTION: Glutaraldehyde-treated crimped bovine pericardial grafts are currently used in aortic graft surgery. These conduits have become good options for these operations, available in different sizes and shapes and at a low cost. OBJECTIVE:To evaluate the results obtained with bovine pericardial grafts for aortic reconstruction, specially concerning late complications. METHOD: Between January 1995 and January 2002, 57 patients underwent different types of aortic reconstruction operations using bovine pericardial grafts. A total of 29 (50.8% were operated on an urgent basis (mostly acute Stanford A dissection and 28 electively. Thoracotomy was performed in three patients for descending aortic replacement (two patients and aortoplasty with a patch in one. All remaining 54 underwent sternotomy, cardiopulmonary bypass and aortic resection. Deep hypothermia and total circulatory arrest was used in acute dissections and arch operations. RESULTS: Hospital mortality was 17.5%. Follow-up was 24.09 months (18.5 to 29.8 months confidence interval and complication-free actuarial survival curve was 92.3% (standard deviation ± 10.6. Two patients lately developed thoracoabdominal aneurysms following previous DeBakey II dissection and one died from endocarditis. One "patch" aortoplasty patient developed local descending aortic pseudoaneurysm 42 months after surgery. All other patients are asymptomatic and currently clinically evaluated with echocardiography and CT scans, showing no complications. CONCLUSION: Use of bovine pericardial grafts in aortic reconstruction surgery is adequate and safe, with few complications related to the conduits.

  6. Bone graft substitutes: past, present, future.

    Directory of Open Access Journals (Sweden)

    Parikh S


    Full Text Available Bone grafts are necessary to provide support, fill voids, and enhance biologic repair of skeletal defects. They are used by orthopaedic surgeons, neurosurgeons, craniofacial surgeons, and periodontists. Bone harvested from donor sites is the gold standard for this procedure. It is well documented that there are limitations and complications from the use of autograft, including the limited quantity and associated chronic donor site pain. Despite the increase in the number of procedures that require bone grafts, there has not been a single ideal bone graft substitute Scientists, surgeons, and medical companies, thus, have a tremendous responsibility to develop biologic alternatives that will enhance the functional capabilities of the bone graft substitute, and potentially reduce or eliminate the need for autograft. This article is an attempt to review the past and existing bone graft substitutes, and future directions of research. The historical data was extracted after thorough review of the literature. The data for the current concepts and future directions was compiled from the Internet, and from direct correspondence with medical companies. Since many products are undergoing clinical trials, and are yet not commercially available, their data cannot be found in literature. The main purpose of this article is to give the reader an idea about the existing market products and products likely to be available in near future.

  7. 革兰阴性菌AmpC酶的检测结果分析%Results in detection of gram negative bacterium AmpC

    Institute of Scientific and Technical Information of China (English)



    目的了解革兰阴性菌产AmpC酶的分布及耐药性. 方法对302株革兰阴性菌用三维试验进行AmpC酶的检测. 结果 302株革兰阴性菌中,AmpC酶检出阳性率最高为阴沟肠杆菌59.5%,而大肠埃希菌、肺炎克雷伯菌较低. 结论对于表型结果高度怀疑产AmpC酶细菌,需进一步进行三维试验和β-内酰胺酶抑制剂效应试验来明确诊断.

  8. Novel anterior cruciate ligament graft fixation device reduces slippage. (United States)

    Lopez, Mandi J; Borne, Allen; Monroe, W Todd; Bommala, Prakash; Kelly, Laura; Zhang, Nan


    Clinically significant laxity occurs in 10%-30% of knees after anterior cruciate ligament reconstruction. Graft slippage and tension loss at the hamstring graft tibial fixation site during and after reconstruction surgery contribute to postoperative joint laxity and are detrimental to long-term knee stability and graft properties. Limiting graft slippage will reduce associated complications. We sought to compare the in vitro mechanical properties and in vivo joint stabilization, postoperative limb use, and graft incorporation of the novel GraftGrab™ (GG) device designed to reduce hamstring graft tibial fixation slippage with the commercially available bioabsorbable Bio-Post™ and spiked washer (BP). Mechanical testing was performed on canine tibia-hamstring graft constructs to quantify initial fixation properties. In vivo joint stabilization, postoperative limb use and graft incorporation of hamstring graft reconstructions were determined in a canine model. Outcomes included tibial translation and ground reaction forces preoperatively and 4 and 8 weeks postoperatively, three-dimensional graft and bone tunnel dimensions at the latter two time points, and graft-bone microstructure, as well as mechanical properties 8 weeks after implantation. Immediately after fixation, all grafts slipped from the BP constructs versus about 30% of GG constructs. In vivo limb use remained low, and tibial translation increased with time in the BP cohort. These results together confirm that initial graft slippage is lower with GG versus BP extracortical hamstring graft tibial fixation. In addition, postoperative recovery and joint stability are more consistent with the GG. This information supports the GG as an alternative to extracortical tibial hamstring graft fixation that has procedural advantages over current implants and reduces graft failure from slippage.

  9. Meshed split skin graft for extensive vitiligo

    Directory of Open Access Journals (Sweden)

    Srinivas C


    Full Text Available A 30 year old female presented with generalized stable vitiligo involving large areas of the body. Since large areas were to be treated it was decided to do meshed split skin graft. A phototoxic blister over recipient site was induced by applying 8 MOP solution followed by exposure to UVA. The split skin graft was harvested from donor area by Padgett dermatome which was meshed by an ampligreffe to increase the size of the graft by 4 times. Significant pigmentation of the depigmented skin was seen after 5 months. This procedure helps to cover large recipient areas, when pigmented donor skin is limited with minimal risk of scarring. Phototoxic blister enables easy separation of epidermis thus saving time required for dermabrasion from recipient site.

  10. Dermal graft correction of extraordinary chordee. (United States)

    Kogan, S J; Reda, E F; Smey, P L; Levitt, S B


    Severe degrees of primary chordee and persistent or recurrent chordee following previous surgical attempts at correction present a challenging problem. Inadequate resection of involved tissues, which may involve all layers of the penile investiture, or recurrent scarring of the ventral skin, Buck's fascia and tunica albuginea is usually the cause. Reoperation to achieve penile straightening often is unsuccessful unless all chordee-bearing tissue is resected extensively. Excision of large segments of tunica albuginea or wide separation of the margins creates a defect that tends to heal by dense scarring unless the defect is bridged by a graft. Various autogenous materials have been used, including blood vessel, fascia, free fat graft, dermis and tunica albuginea, as well as prosthestic materials, such as polytetrafluoroethylene, with varying results. A series of patients with extensive chordee is presented in whom tunical resection was necessary to achieve penile straightening. The results of free dermal graft replacement of the tunica are reported.

  11. A Temporal-Specific and Transient cAMP Increase Characterizes Odorant Classical Conditioning (United States)

    Cui, Wen; Smith, Andrew; Darby-King, Andrea; Harley, Carolyn W.; McLean, John H.


    Increases in cyclic adenosine monophosphate (cAMP) are proposed to initiate learning in a wide variety of species. Here, we measure changes in cAMP in the olfactory bulb prior to, during, and following a classically conditioned odor preference trial in rat pups. Measurements were taken up to the point of maximal CREB phosphorylation in olfactory…

  12. Design of cAMP-CRP-activated promoters in Escherichia coli

    DEFF Research Database (Denmark)

    Valentin-Hansen, P; Holst, B; Søgaard-Andersen, L


    We have studied the deoP2 promoter of Escherichia coli to define features that are required for optimal activation by the complex of adenosine 3',5' monophosphate (cAMP) and the cAMP receptor protein (CRP). Systematic mutagenesis of deoP2 shows that the distance between the CRP site and the -10...

  13. A cell-autonomous molecular cascade initiated by AMP-activated protein kinase represses steroidogenesis. (United States)

    Abdou, Houssein S; Bergeron, Francis; Tremblay, Jacques J


    Steroid hormones regulate essential physiological processes, and inadequate levels are associated with various pathological conditions. In testosterone-producing Leydig cells, steroidogenesis is strongly stimulated by luteinizing hormone (LH) via its receptor leading to increased cyclic AMP (cAMP) production and expression of the steroidogenic acute regulatory (STAR) protein, which is essential for the initiation of steroidogenesis. Steroidogenesis then passively decreases with the degradation of cAMP into AMP by phosphodiesterases. In this study, we show that AMP-activated protein kinase (AMPK) is activated following cAMP-to-AMP breakdown in MA-10 and MLTC-1 Leydig cells. Activated AMPK then actively inhibits cAMP-induced steroidogenesis by repressing the expression of key regulators of steroidogenesis, including Star and Nr4a1. Similar results were obtained in Y-1 adrenal cells and in the constitutively steroidogenic R2C cells. We have also determined that maximum AMPK activation following stimulation of steroidogenesis in MA-10 Leydig cells occurs when steroid hormone production has reached a plateau. Our data identify AMPK as a molecular rheostat that actively represses steroid hormone biosynthesis to preserve cellular energy homeostasis and prevent excess steroid production.

  14. A novel conditional genetic system reveals that increasing neuronal cAMP enhances memory and retrieval

    NARCIS (Netherlands)

    Isiegas, Carolina; McDonough, Conor; Huang, Ted; Havekes, Robbert; Fabian, Sara; Wu, Long-Jun; Xu, Hui; Zhao, Ming-Gao; Kim, Jae-Ick; Lee, Yong-Seok; Lee, Hye-Ryeon; Ko, Hyoung-Gon; Lee, Nuribalhae; Choi, Sun-Lim; Lee, Jeong-Sik; Son, Hyeon; Zhuo, Min; Kaang, Bong-Kiun; Abel, Ted


    Consistent evidence from pharmacological and genetic studies shows that cAMP is a critical modulator of synaptic plasticity and memory formation. However, the potential of the cAMP signaling pathway as a target for memory enhancement remains unclear because of contradictory findings from pharmacolog

  15. cAMP-dependent signaling regulates the adipogenic effect of n-6 polyunsaturated fatty acids

    DEFF Research Database (Denmark)

    Madsen, Lise; Pedersen, Lone Møller; Liaset, Bjørn


    The effect of n-6 polyunsaturated fatty acids (n-6 PUFAs) on adipogenesis and obesity is controversial. Using in vitro cell culture models, we show that n-6 PUFAs was pro-adipogenic under conditions with base-line levels of cAMP, but anti-adipogenic when the levels of cAMP were elevated. The anti...

  16. Targeting brain tumor cAMP: the case for sex-specific therapeutics

    Directory of Open Access Journals (Sweden)

    Nicole M Warrington


    Full Text Available A relationship between cyclic adenosine 3’, 5’-monophosphate (cAMP levels and brain tumor biology has been evident for nearly as long as cAMP and its synthetase, adenylate cyclase (ADCY have been known. The importance of the pathway in brain tumorigenesis has been demonstrated in vitro and in multiple animal models. Recently, we provided human validation for a cooperating oncogenic role for cAMP in brain tumorigenesis when we found that SNPs in ADCY8 were correlated with glioma (brain tumor risk in individuals with Neurofibromatosis type 1 (NF1. Together, these studies provide a strong rationale for targeting cAMP in brain tumor therapy. However, the cAMP pathway is well known to be sexually dimorphic, and SNPs in ADCY8 affected glioma risk in a sex-specific fashion, elevating the risk for females while protecting males. The cAMP pathway can be targeted at multiple levels in the regulation of its synthesis and degradation. Sex differences in response to drugs that target cAMP regulators indicate that successful targeting of the cAMP pathway for brain tumor patients is likely to require matching specific mechanisms of drug action with patient sex.

  17. Reciprocal regulation of insulin and plasma 5'-AMP in glucose homeostasis in mice. (United States)

    Xia, Lin; Wang, Zhongqiu; Zhang, Ying; Yang, Xiao; Zhan, Yibei; Cheng, Rui; Wang, Shiming; Zhang, Jianfa


    A previous investigation has demonstrated that plasma 5'-AMP (pAMP) exacerbates and causes hyperglycemia in diabetic mice. However, the crosstalk between pAMP and insulin signaling to regulate glucose homeostasis has not been investigated in depth. In this study, we showed that the blood glucose level was more dependent on the ratio of insulin to pAMP than on the absolute level of these two factors. Administration of 5'-AMP significantly attenuated the insulin-stimulated insulin receptor (IR) autophosphorylation in the liver and muscle tissues, resulting in the inhibition of downstream AKT phosphorylation. A docking analysis indicated that adenosine was a potential inhibitor of IR tyrosine kinase. Moreover, the 5'-AMP treatment elevated the ATP level in the pancreas and in the isolated islets, stimulating insulin secretion and increasing the plasma level of insulin. The insulin administration decreased the 5'-AMP-induced hyper-adenosine level by the up-regulation of adenosine kinase activities. Our results indicate that blood glucose homeostasis is reciprocally regulated by pAMP and insulin.

  18. Chemotaxis to cyclic AMP and folic acid is mediated by different G proteins in Dictyostelium discoideum

    NARCIS (Netherlands)

    Kesbeke, Fanja; Haastert, Peter J.M. van; Wit, René J.W. de; Snaar-Jagalska, B. Ewa


    Mutant Frigid A (fgdA) of Dictyostelium discoideum is defective in a functional Gα2 subunit of a G protein and is characterized by a complete blockade of the cyclic AMP-mediated sensory transduction steps, including cyclic AMP relay, chemotaxis and the cyclic GMP response. Folic acid-mediated transm

  19. cAMP-independent signal pathways stimulate hyphal morphogenesis in Candida albicans. (United States)

    Parrino, Salvatore M; Si, Haoyu; Naseem, Shamoon; Groudan, Kevin; Gardin, Justin; Konopka, James B


    The fungal pathogen Candida albicans can transition from budding to hyphal growth, which promotes biofilm formation and invasive growth into tissues. Stimulation of adenylyl cyclase to form cAMP induces hyphal morphogenesis. The failure of cells lacking adenylyl cyclase (cyr1Δ) to form hyphae has suggested that cAMP signaling is essential for hyphal growth. However, cyr1Δ mutants also grow slowly and have defects in morphogenesis, making it unclear whether hyphal inducers must stimulate cAMP, or if normal basal levels of cAMP are required to maintain cellular health needed for hyphal growth. Interestingly, supplementation of cyr1Δ cells with low levels of cAMP enabled them to form hyphae in response to the inducer N-acetylglucosamine (GlcNAc), suggesting that a basal level of cAMP is sufficient for stimulation. Furthermore, we isolated faster-growing cyr1Δ pseudorevertant strains that can be induced to form hyphae even though they lack cAMP. The pseudorevertant strains were not induced by CO2 , consistent with reports that CO2 directly stimulates adenylyl cyclase. Mutational analysis showed that induction of hyphae in a pseudorevertant strain was independent of RAS1, but was dependent on the EFG1 transcription factor that acts downstream of protein kinase A. Thus, cAMP-independent signals contribute to the induction of hyphal responses.

  20. Global and local missions of cAMP signaling in neural plasticity, learning and memory

    Directory of Open Access Journals (Sweden)

    Daewoo eLee


    Full Text Available The fruit fly Drosophila melanogaster has been a popular model to study cAMP signaling and resultant behaviors due to its powerful genetic approaches. All molecular components (AC, PDE, PKA, CREB, etc essential for cAMP signaling have been identified in the fly. Among them, adenylyl cyclase (AC gene rutabaga and phosphodiesterase (PDE gene dunce have been intensively studied to understand the role of cAMP signaling. Interestingly, these two mutant genes were originally identified on the basis of associative learning deficits. This commentary summarizes findings on the role of cAMP in Drosophila neuronal excitability, synaptic plasticity and memory. It mainly focuses on two distinct mechanisms (global versus local regulating excitatory and inhibitory synaptic plasticity related to cAMP homeostasis. This dual regulatory role of cAMP is to increase the strength of excitatory neural circuits on one hand, but to act locally on postsynaptic GABA receptors to decrease inhibitory synaptic plasticity on the other. Thus the action of cAMP could result in a global increase in the neural circuit excitability and memory. Implications of this cAMP signaling related to drug discovery for neural diseases are also described.

  1. The Cyclic Nucleotide Specificity of Three cAMP Receptors in Dictyostelium

    NARCIS (Netherlands)

    Johnson, Ronald L.; Haastert, Peter J.M. van; Kimmel, Alan R.; Saxe III, Charles L.; Jastorff, Bernd; Devreotes, Peter N.


    cAMP receptors mediate signal transduction pathways during development in Dictyostelium. A cAMP receptor (cAR1) has been cloned and sequenced (Klein, P., Sun, T. J., Saxe, C. L., Kimmel, A. R., Johnson, R. L., and Devreotes, P. N. (1988) Science 241, 1467-1472) and recently several other cAR genes h

  2. Functional involvement of Annexin-2 in cAMP induced AQP2 trafficking.

    NARCIS (Netherlands)

    Tamma, G.; Procino, G.; Mola, M.G.; Svelto, M.; Valenti, G.


    Annexin-2 is required for the apical transport in epithelial cells. In this study, we investigated the involvement of annexin-2 in cAMP-induced aquaporin-2 (AQP2) translocation to the apical membrane in renal cells. We found that the cAMP-elevating agent forskolin increased annexin-2 abundance in th

  3. Genetic Environment and Transcription of ampC in an Acinetobacter baumannii Clinical Isolate


    Segal, Heidi; Nelson, E.C.; Elisha, B. Gay


    An ampC gene was cloned from a clinical isolate of Acinetobacter baumannii (strain RAN). DNA sequencing and primer extension studies showed that ampC is transcribed from a promoter contained within a putative insertion sequence element which has been found to abut several different genes in Acinetobacter spp.

  4. The cAMP Signaling and MAP Kinase Pathways in Plant Pathogenic Fungi

    NARCIS (Netherlands)

    Mehrabi, R.; Zhao, X.; Kim, Y.; Xu, J.R.


    The key components of the well conserved cyclic AMP signaling and MAP kinase pathways have been functionally characterized in the corn smut Ustilago maydis, rice blast fungus Magnaporthe grisea, and a few other fungal pathogens. In general, the cAMP signaling and the MAP kinase cascade homologous to

  5. Development of antimicrobial peptides (AMPs) for use in self-decontaminating coatings. (United States)

    Fulmer, Preston A; Lundin, Jeffrey G; Wynne, James H


    Antimicrobial peptides (AMPs) are a class of short polypeptides usually associated with the host organism's innate immune system. AMPs have been identified in a wide range of host organisms, including plants, amphibians, fish, and humans. These peptides usually consist of 30-100 amino acids and are most often cationic. In addition to a net positive charge, AMPs often are amphipathic, containing both hydrophobic and hydrophilic domains. This property allows for increased interaction with and insertion into negatively charged cell walls and membranes of microbes. Because of the prevalence of antibiotic resistance among common human pathogens, recent research into AMPs has revolved around the attempt to increase the availability of drugs to which microbes are susceptible. Because the mechanism of kill for AMPs is different from that of most conventional antibiotics, which tend to be very specific in their targets, AMPs are thought to be a very attractive future substitute for traditional antibiotics. The development of novel self-decontaminating surfaces containing two AMPs previously isolated from Chrysophrys major is reported. These AMPs, Chrysophsin-1 and -3, demonstrated 1-4 logs kill of both Gram-positive and Gram-negative bacteria when incorporated into control acrylic coating systems.

  6. The effect of neuropeptides on vessel tone and cAMP production

    DEFF Research Database (Denmark)

    Yao, W; Sheikh, S P; Ottesen, B;


    The effect of VIP, PHM, PHV, PACAP-27, and PACAP-38 on vessel tone and cAMP production was investigated in rabbit ovarian arteries in vitro. The peptides (10(-7)M) induced a significant relaxation on NA-precontracted vessels and displayed similar potencies. The cAMP accumulation induced by PACAP-...

  7. 质粒介导AmpC酶的研究进展%Research progress on plasmid-mediated AmpC beta-lactamases

    Institute of Scientific and Technical Information of China (English)

    王林峰; 王选锭


    @@ AmpC酶是革兰阴性杆菌产生的最重要的β-内酰胺酶之一,因其能产生对第三代头孢、单环类、头霉素类等β-内酰胺类抗生素的耐药性,且不受临床常用的β-内酰胺酶抑制剂抑制而受到重视.特别是1988年发现质粒介导的AmpC酶以来,随着越来越多种类的质粒介导AmpC酶在世界各地相继被发现,人们已意识到,AmpC酶对人类健康的威胁不再仅仅局限于引起单个病例的难治性感染,而且有可能通过质粒传递导致AmpC酶基因的广泛传播,造成全球范围耐药菌株流行.本文将详细介绍质粒介导AmpC酶的流行病学、生化特征、检测及防治等.

  8. Detection of AmpC enzyme in gram-negative bacteria%革兰阴性杆菌中AmpC酶的检测

    Institute of Scientific and Technical Information of China (English)



    AmpC酶是由革兰阴性杆菌产生的不被克拉维酸抑制,属β-内酰胺酶Bush I型酶或Ambler C类酶,能水解青霉素类,1、2、3代头孢菌素类和单环类的β-内酰胺酶.AmpC不但由染色体编码,而且也可由质粒介导,质粒介导的AmpC酶的出现增强了耐药菌株的横向传播.高产AmpC酶菌株引起的感染使抗感染治疗面临严峻挑战.AmpC酶检测有头孢西汀三维试验、等电聚焦电泳和PCR等方法,但难以在临床细菌室开展,近年报道的几种AmpC酶表型筛选法是一种简便、有效的方法,可供各级临床实验室选用.

  9. The catalytic subunit of cAMP-dependent protein kinase induces expression of genes containing cAMP-responsive enhancer elements. (United States)

    Riabowol, K T; Fink, J S; Gilman, M Z; Walsh, D A; Goodman, R H; Feramisco, J R


    Transcriptional regulation of eukaryotic genes by cyclic AMP requires a cAMP-dependent protein kinase (A kinase). Two hypotheses have been proposed to explain how the holoenzyme of the A kinase induces transcription. The regulatory subunits of the A kinase, which bind cAMP and DNA, and have amino-acid homology with the Escherichia coli catabolite activator protein could directly stimulate gene expression. Alternatively, phosphorylation by the catalytic subunits could induce transcription by activating proteins involved in gene transcription. To distinguish between these models, we microinjected purified preparations of the catalytic and regulatory subunits of A kinase into tissue culture cells and monitored expression of a stably integrated fusion gene containing a cAMP-responsive human promoter fused to a bacterial reporter gene, or of the endogenous c-fos gene. The catalytic subunit stimulated expression of these genes, whereas the regulatory subunit did not. These results indicate that the catalytic subunit of A kinase is sufficient to induce expression of two cAMP-responsive genes, without increasing levels of cAMP.

  10. Autologous Fat Grafting for Whole Breast Reconstruction

    Directory of Open Access Journals (Sweden)

    Benjamin H. L. Howes, MBBS


    Full Text Available Summary: This is the first reported case of a patient who had a single-stage large-volume breast reconstruction with autologous fat grafting, following rotation flap approach (RoFA mastectomy. The purpose of this case study was to evaluate the viability of reconstruction of the breast by autologous fat grafting alone, in the context of RoFA mastectomy. The hypothesis was that there would be minimal interval loss of autologous fat on the whole breast reconstruction side. Right RoFA mastectomy was used for resection of an invasive primary breast cancer and resulted in the right breast skin envelope. Eleven months later, the patient underwent grafting of 400 ml of autologous fat into the skin envelope and underlying pectoralis major muscle. Outcome was assessed by using a validated 3D laser scan technique for quantitative breast volume measurement. Other outcome measures included the BREAST-Q questionnaire and 2D clinical photography. At 12-month follow-up, the patient was observed to have maintenance of volume of the reconstructed breast. Her BREAST-Q scores were markedly improved compared with before fat grafting, and there was observable improvement in shape, contour, and symmetry on 2D clinical photography. The 2 new techniques, RoFA mastectomy and large-volume single-stage autologous fat grafting, were used in combination to achieve a satisfactory postmastectomy breast reconstruction. Novel tools for measurement of outcome were the 3D whole-body laser scanner and BREAST-Q questionnaire. This case demonstrates the potential for the use of fat grafting for reconstruction. Outcomes in a larger patient populations are needed to confirm these findings.

  11. 接枝改性尼龙66织物的吸湿性和燃烧成炭性%Hydrophilicity and char formation of nylon 66 by chemical grafting

    Institute of Scientific and Technical Information of China (English)

    赵倩; 谷晓昱; 姜鹏; 唐浩; 张胜


    The 2-acryloylamino-2-methyl-l-propanesulfonic acid (AMPS) and 2-hydroxyethyl methacr/late (HEMA) are introduced onto the surface of nylon 66 fabric by chemical induced grafting.Influences of monomer concentration,reaction temperature and time on grafting yield are investigated.The optimum reaction process are:the monomer concentration 15%,and reaction at 80 ℃ for 2 h.The chemical structure of grafted PA 66 fabric is characterized by attenuated total reflection infrared spectroscopy (ATR-FTIR) and scanning electron microscope (SEM),which reveals AMPS and HEMA have been successfully grafted onto the surface of nylon 66 fabric.Thermal behavior of grafted sample is evaluated by TGA,which shows that the grafted sample features reduced decomposition temperature and increased char residue compared with the untreated sample.The hydrophilicity of the sample is improved,the wetting time decreases from 417.3 s to 25.2 s at grafting yield of 8.8%.The dripping tendency is reduced significantly and the mechanical properties are improved slightly.%采用化学接枝法将2-丙烯酰氨基-2-甲基-1-丙磺酸(AMPS)和甲基丙烯酸羟乙酯(HEMA)共同接枝到尼龙66织物表面,研究单体质量分数、反应时间和反应温度对接枝率的影响.结果显示,优化的接枝反应条件为:单体质量分数15%,反应温度80℃,反应时间2h;采用衰减全反射-红外光谱(ATR-FTIR)以及扫描电镜(SEM)对接枝织物进行结构表征,表明AMPS与HEMA成功地接枝到织物表面;热重分析(TGA)表明接枝后织物的热分解温度降低,残炭率提高.织物接枝后吸湿性提高,接枝率为8.8%时,润湿时间从417.3 s降低到25.2 s;熔滴数明显减少,机械性能有所提高.

  12. Amp: A modular approach to machine learning in atomistic simulations (United States)

    Khorshidi, Alireza; Peterson, Andrew A.


    Electronic structure calculations, such as those employing Kohn-Sham density functional theory or ab initio wavefunction theories, have allowed for atomistic-level understandings of a wide variety of phenomena and properties of matter at small scales. However, the computational cost of electronic structure methods drastically increases with length and time scales, which makes these methods difficult for long time-scale molecular dynamics simulations or large-sized systems. Machine-learning techniques can provide accurate potentials that can match the quality of electronic structure calculations, provided sufficient training data. These potentials can then be used to rapidly simulate large and long time-scale phenomena at similar quality to the parent electronic structure approach. Machine-learning potentials usually take a bias-free mathematical form and can be readily developed for a wide variety of systems. Electronic structure calculations have favorable properties-namely that they are noiseless and targeted training data can be produced on-demand-that make them particularly well-suited for machine learning. This paper discusses our modular approach to atomistic machine learning through the development of the open-source Atomistic Machine-learning Package (Amp), which allows for representations of both the total and atom-centered potential energy surface, in both periodic and non-periodic systems. Potentials developed through the atom-centered approach are simultaneously applicable for systems with various sizes. Interpolation can be enhanced by introducing custom descriptors of the local environment. We demonstrate this in the current work for Gaussian-type, bispectrum, and Zernike-type descriptors. Amp has an intuitive and modular structure with an interface through the python scripting language yet has parallelizable fortran components for demanding tasks; it is designed to integrate closely with the widely used Atomic Simulation Environment (ASE), which

  13. cAMP prevents TNF-induced apoptosis through inhibiting DISC complex formation in rat hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharjee, Rajesh [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (United States); Xiang, Wenpei [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (United States); Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People' s Republic of China (China); Wang, Yinna [Vascular Medicine Institute, University of Pittsburgh School of Medicine, 10051-5A BST 3, 3501 Fifth Avenue, Pittsburgh, PA 15261 (United States); Zhang, Xiaoying [Department of Medicine/Endocrinology Division, University of Pittsburgh Medical Center, 200 Lothrop St., Pittsburgh, PA 15213 (United States); Billiar, Timothy R., E-mail: [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (United States)


    Highlights: Black-Right-Pointing-Pointer cAMP blocks cell death induced by TNF and actinomycin D in cultured hepatocytes. Black-Right-Pointing-Pointer cAMP blocks NF-{kappa}B activation induced by TNF and actinomycin D. Black-Right-Pointing-Pointer cAMP blocks DISC formation following TNF and actinomycin D exposure. Black-Right-Pointing-Pointer cAMP blocks TNF signaling at a proximal step. -- Abstract: Tumor necrosis factor {alpha} (TNF) is a pleiotropic proinflammatory cytokine that plays a role in immunity and the control of cell proliferation, cell differentiation, and apoptosis. The pleiotropic nature of TNF is due to the formation of different signaling complexes upon the binding of TNF to its receptor, TNF receptor type 1 (TNFR1). TNF induces apoptosis in various mammalian cells when the cells are co-treated with a transcription inhibitor like actinomycin D (ActD). When TNFR1 is activated, it recruits an adaptor protein, TNF receptor-associated protein with death domain (TRADD), through its cytoplasmic death effector domain (DED). TRADD, in turn, recruits other signaling proteins, including TNF receptor-associated protein 2 (TRAF2) and receptor-associated protein kinase (RIPK) 1, to form a complex. Subsequently, this complex combines with FADD and procaspase-8, converts into a death-inducing signaling complex (DISC) to induce apoptosis. Cyclic AMP (cAMP) is a second messenger that regulates various cellular processes such as cell proliferation, gene expression, and apoptosis. cAMP analogues are reported to act as anti-apoptotic agents in various cell types, including hepatocytes. We found that a cAMP analogue, dibutyryl cAMP (db-cAMP), inhibits TNF + ActD-induced apoptosis in rat hepatocytes. The protein kinase A (PKA) inhibitor KT-5720 reverses this inhibitory effect of cAMP on apoptosis. Cytoprotection by cAMP involves down-regulation of various apoptotic signal regulators like TRADD and FADD and inhibition of caspase-8 and caspase-3 cleavage. We also found

  14. Culture of graft-infiltrating cells from cryopreserved endomyocardial biopsies

    NARCIS (Netherlands)

    G.A. Patijn (G.); L.M.B. Vaessen (Leonard); W. Weimar (Willem); F.H.J. Claas (Frans); N.H.P.M. Jutte (Nicolet)


    textabstractGraft-infiltrating cells can be cultured from fresh endomyocardial biopsies (EMB) taken after heart transplantation to determine their growth patterns, phenotypic composition, and functional characteristics for clinical or scientific purposes. In this study we investigated whether graft-

  15. Sulfonated hydrocarbon graft architectures for cation exchange membranes

    DEFF Research Database (Denmark)

    Nielsen, Mads Møller; Jankova Atanasova, Katja; Hvilsted, Søren


    A synthetic strategy to hydrocarbon graft architectures prepared from a commercial polysulfone and aimed as ion exchange membrane material is proposed. Polystyrene is grafted from a polysulfone macroinitiator by atom transfer radical polymerization, and subsequently sulfonated with acetyl sulfate...

  16. Graft patency in off-pump and conventional coronary artery bypass grafting for treatment of triple vessel coronary disease

    Institute of Scientific and Technical Information of China (English)

    胡盛寿; 王小启; 宋云虎; 吕锋


    Objective To compare graft patency in off-pump and conventional coronary artery bypass grafting by using the transit time flow meter in the treatment of triple vessel coronary artery disease. Methods Between June 2000 and April 2001, 60 patients with triple vessel coronary artery disease underwent coronary artery bypass grafting. They were divided into two groups: off-pump and conventional coronary artery bypass. All completed grafts were tested intraoperatively using Transit Time Flow Measurement (TTFM). Preoperative and postoperative variables of the two groups were also compared. Results There were no significant differences in sex, age, weight, acute or remote myocardial infarction, hypertension, diabetes and type of bypass grafts between the two groups. The number of bypass grafts and the assisted respiratory time of the off-pump coronary artery bypass grafting (OPCAB) group were significantly less than those of the conventional coronary artery bypass grafting (CCABG) group. The flow and pulsatile index (PI) of the left anterior descending artery bypass grafts and the right coronary artery bypass grafts were not significantly different between the OPCAB and CCABG groups. The flow of OM in the CCABG group with the multiple anastomosis site of sequential grafts was higher than that in the OPCAB group. Diffused narrow coronary artery bypass grafts in both groups had less flow.Conclusion No signficant differences in graft patency were observed in patients with triple vessel coronary artery disease who had undergone OPCAB or CCABG.

  17. Structural Elucidation and Antitumor Activity of Polysaccharide AMP-1 from Atractylodis macrocephalae K.

    Institute of Scientific and Technical Information of China (English)

    SHAN,Jun-Jie; KE,Wei; DENG,Jun-E; TIAN,Geng-Yuan


    A polysaccharide named as AMP-1 was isolated from the root ofAtractylodis macrocephalae Koidz, and purified by ethanol fractionation and gel filtration. The homogeneity of AMP-1 was determined by HPLC and capillary electrophoresis that gave a single peak.AMP-1 is composed of galactose and mannose in a molar ratio of 1.0:1.9. Its molecular weight is3.8× 103. The structure of glycan was elucidated by IR, 1H NMR, 13C NMR and methylation analysis, and on the basis of the results was suggested that AMP-1 contain a backbone of β- (1→2)-D-galactose residues with branches of single β-D-mannose residue being substituted at the 0-6. Bioactivity assay of AMP-1 showed that it could inhibit growth of Sarcoma 180 and Lewis pulmonary carcinoma implanted in mice.

  18. Cyclic AMP activates the mitogen-activated protein kinase cascade in PC12 cells

    DEFF Research Database (Denmark)

    Frödin, M; Peraldi, P; Van Obberghen, E


    Mitogen-activated protein (MAP) kinases are activated in response to a large variety of extracellular signals, including growth factors, hormones, and neurotransmitters, which activate distinct intracellular signaling pathways. Their activation by the cAMP-dependent pathway, however, has not been...... reported. In rat pheochromocytoma PC12 cells, we demonstrate here a stimulation of the MAP kinase isozyme extracellular signal-regulated kinase 1 (ERK1) following elevation of intracellular cAMP after exposure of the cells to isobutylmethylxanthine, cholera toxin, forskolin, or cAMP-analogues. cAMP acted...... synergistically with phorbol ester, an activator of protein kinase C, in the stimulation of ERK1. In accordance with this observation, the peptide neurotransmitter pituitary adenylate cyclase-activating polypeptide 38 (PACAP38), which stimulates cAMP production as well as phosphatidylinositol breakdown in PC12...

  19. AMP-Conjugated Quantum Dots: Low Immunotoxicity Both In Vitro and In Vivo (United States)

    Dai, Tongcheng; Li, Na; Liu, Lu; Liu, Qin; Zhang, Yuanxing


    Quantum dots (QDs) are engineered nanoparticles that possess special optical and electronic properties and have shown great promise for future biomedical applications. In this work, adenosine 5'-monophosphate (AMP), a small biocompatible molecular, was conjugated to organic QDs to produce hydrophilic AMP-QDs. Using macrophage J774A.1 as the cell model, AMP-QDs exhibited both prior imaging property and low toxicity, and more importantly, triggered limited innate immune responses in macrophage, indicating low immunotoxicity in vitro. Using BALB/c mice as the animal model, AMP-QDs were found to be detained in immune organs but did not evoke robust inflammation responses or obvious histopathological abnormalities, which reveals low immunotoxicity in vivo. This work suggests that AMP is an excellent surface ligand with low immunotoxicity, and potentially used in surface modification for more extensive nanoparticles.

  20. The effect of in vitro procedures on cyclic AMP accumulation in human leucocytes

    DEFF Research Database (Denmark)

    Johansen, Torben; Friis, U G; Rasmussen, A K;


    The aim of this study was to investigate the effect of various methodological procedures or protocols on cyclic AMP formation in human leucocytes. The data showed that: (1) ATP content and lactate production was unaffected by hypotonic lysis during leucocyte isolation; (2) there was a linear...... relation between cell number/sample and the production of cyclic adenosine 3':5'-monophosphate (cAMP); (3) the interindividual variation markedly affected cAMP production during long observation periods (years), whereas day-to-day variation within a week was less important; (4) whole blood could be stored...... for up to 4 h (at 4 degrees C or 23 degrees C) without affecting cAMP accumulation; (5) isolated MNL could be stored for up to 2 h (at 4 degrees C) without affecting cAMP accumulation; and finally that (6) choice and concentration of phosphodiesterase inhibitors markedly influenced the basal...

  1. AmpC酶的检测技术研究进展

    Institute of Scientific and Technical Information of China (English)




  2. Role of AC-cAMP-PKA Cascade in Antidepressant Action of Electroacupuncture Treatment in Rats

    Directory of Open Access Journals (Sweden)

    Jian-hua Liu


    Full Text Available Adenylyl cyclase (AC-cyclic adenosine monophosphate (cAMP-cAMP-dependent protein kinase A (PKA cascade is considered to be associated with the pathogenesis and treatment of depression. The present study was conducted to explore the role of the cAMP cascade in antidepressant action of electroacupuncture (EA treatment for chronic mild stress (CMS-induced depression model rats. The results showed that EA improved significantly behavior symptoms in depression and dysfunction of AC-cAMP-PKA signal transduction pathway induced by CMS, which was as effective as fluoxetine. Moreover, the antidepressant effects of EA rather than Fluoxetine were completely abolished by H89, a specific PKA inhibitor. Consequently, EA has a significant antidepressant treatment in CMS-induced depression model rats, and AC-cAMP-PKA signal transduction pathway is crucial for it.

  3. Patency rates and the role of newer grafts in coronary artery bypass grafting. (United States)

    Rai, Mridula; Rustagi, Tarun


    Coronary artery bypass grafting (CABG) was one of major surgical advances of the 20th century and it has proven to be one of the most effective and long-lasting therapies in the treatment of ischemic heart disease. Despite its success, the long-term outcome of coronary bypass surgery is strongly influenced by the fate of the vascular conduits used. We seek to review the emerging role and patency rates of newer arterial grafts in comparison with the traditional saphenous vein grafts.

  4. The melatonin agonist ramelteon induces duration-dependent clock gene expression through cAMP signaling in pancreatic INS-1 β-cells.

    Directory of Open Access Journals (Sweden)

    Keiji Nishiyama

    Full Text Available Prolonged exposure to melatonin improves glycemic control in animals. Although glucose metabolism is controlled by circadian clock genes, little is known about the role of melatonin signaling and its duration in the regulation of clock gene expression in pancreatic β-cells. Activation of MT1 and MT2 melatonin receptors inhibits cAMP signaling, which mediates clock gene expression. Therefore, this study investigated exposure duration-dependent alterations in cAMP element-binding protein (CREB phosphorylation and clock gene expression that occur during and after exposure to ramelteon, a selective melatonin agonist used to treat insomnia. In rat INS-1 cells, a pancreatic β-cell line endogenously expressing melatonin receptors, ramelteon persistently decreased CREB phosphorylation during the treatment period (2-14 h, whereas the subsequent washout induced an enhancement of forskolin-stimulated CREB phosphorylation in a duration- and concentration-dependent manner. This augmentation was blocked by forskolin or the melatonin receptor antagonist luzindole. Similarly, gene expression analyses of 7 clock genes revealed the duration dependency of the effects of ramelteon on Rev-erbα and Bmal1 expression through melatonin receptor-mediated cAMP signaling; longer exposure times (14 h resulted in greater increases in the expression and signaling of Rev-erbα, which is related to β-cell functions. Interestingly, this led to amplified oscillatory Rev-erbα and Bmal1 expression after agonist washout and forskolin stimulation. These results provide new insights into the duration-dependent effects of ramelteon on clock gene expression in INS-1 cells and may improve the understanding of its effect in vivo. The applicability of these results to pancreatic islets awaits further investigation.

  5. An experimental study on inhibiting graft rejection following high-risk penetrating keratoplasty by CD25 siRNA nanocarrier in rats

    Directory of Open Access Journals (Sweden)

    Yun-jie SHI


    Full Text Available Objective To investigate the effects of CD25 siRNA nanoparticles against immune rejection and prolongation of corneal graft survival time after high-risk corneal grafting in rats. Methods Orthotopic corneal transplantation was performed in SD rats with alkali burned corneas to mimic high-risk rat models. Donor cornea (Wistar rats was grafted into the right cornea of SD recipients on day 14 after alkali burn. The grafted rats were randomly divided into control group (Group A, EntransterTM-control CD25siRNA instillation treatment (Group B, EntransterTM-CD25siRNA instillation treatment (Group C and EntransterTM-CD25siRNA twice instillation treatment (Group D, first administration at 2-hour post-surgery and second on day 7 post-surgery. The recipient eyes were examined using a slit lamp microscope. Then, the mean survival time and rejection index (RI were calculated. The morphologies of grafts were microscopically examined with HE staining, and TEM. CD25 expression after operation was determined by quantitative RT-PCR and immunohistochemistry. Results The survival curves of transplanted cornea showed that the mean survival time in rats of groups C and D was significantly longer than that in groups A and B (P<0.05. No significant difference was found in survival time between group A and group B, and the same between group C and group D. The grafts in groups A and B showed obvious edema and thickening, with irregular arrangement of collagen fibers and infiltration of a large amount of inflammatory cells. Immunohistochemical results showed that expression of CD25 was found in the corneal epithelium, stroma and endothelium in all rats, and higher CD25 expression was observed in groups A and B. Transmission electron microscopy revealed that the degree of stromal fibroblast apoptosis and necrosis in corneal graft was obviously lower in groups C and D than that of groups A and B, with a significant statistical difference. The expression of CD25 m

  6. Electrical Properties of n-Butyl Acrylate-Grafted Polyethylene

    Energy Technology Data Exchange (ETDEWEB)

    Lee, C.R.; Oh, W.J.; Suh, K.S. [Korea University (Korea, Republic of)


    The electrical properties of n-butyl acrylate-grafted polyethylene (PE-g-nBA) were investigated. In PE-g-nBA, hetero charge founded in LDPE slightly increased due to the nBA grafting. Conduction currents decreased with the increase of nBA graft ratio. AC breakdown strength increased and water treeing length decreased with the increase of graft ratio in PE-g-nBA. (author). 4 refs., 6 figs.

  7. Hemocompatibility of Chitosan/poly(acrylic acid) Grafted Polyurethane Tubing


    Lee, Hyun-Su; Tomczyk, Nancy; Kandel, Judith; Composto, Russell J.; Eckmann, David M.


    The activation and adhesion of platelets or whole blood exposed to chitosan (CH) grafted surfaces is used to evaluate the hemocompatibility of biomaterials. The biomaterial surfaces are polyurethane (PU) tubes grafted with an inner poly(acrylic acid) (PAA) and an outer CH or quaternary ammonium modified CH (CH-Q) brush. The CH, CH-Q and PAA grafted layers were characterized by ellipsometry and fluorescence microscopy. Material wear tests demonstrate that CH (CH-Q) is stably grafted onto PU tu...

  8. Striatal grafts in a rat model of Huntington's disease

    DEFF Research Database (Denmark)

    Guzman, R; Meyer, M; Lövblad, K O;


    Survival and integration into the host brain of grafted tissue are crucial factors in neurotransplantation approaches. The present study explored the feasibility of using a clinical MR scanner to study striatal graft development in a rat model of Huntington's disease. Rat fetal lateral ganglionic...... eminences grown as free-floating roller-tube cultures can be successfully grafted in a rat Huntington model and that a clinical MR scanner offers a useful noninvasive tool for studying striatal graft development....

  9. Plasma Induced Grafting of PMMA onto Titanium Dioxide Powder

    Institute of Scientific and Technical Information of China (English)

    Zhong Shaofeng; Meng Yuedong; Ou Qiongrong; Xu Xu


    Grafting of polymer of methyl methacrylate (PMMA) onto titanium dioxide powder is investigated in this paper. The graft polymerization reaction is induced by dielectric-barrierdischarge produced N2 plasma treatment of titanium dioxide surfaces. IR, XPS and TGA results show that PMMA is grafted onto the surfaces of titanium dioxide powder. And crystal structure of the titanium dioxide powder observed with XRD spectra is unchanged after plasma graft polymerization.

  10. cAMP-binding proteins in medullary tubules from rat kidney: effect of ADH

    Energy Technology Data Exchange (ETDEWEB)

    Gapstur, S.M.; Homma, S.; Dousa, T.P.


    Little is known of the regulatory steps in the cellular action of vasopressin (AVP) on the renal epithelium, subsequent to the cAMP generation. We studied cAMP-binding proteins in the medullary collecting tubule (MCT) and the thick ascending limb of Henle's loop (MTAL) microdissected from the rat kidney by use of photoaffinity labeling. Microdissected tubules were homogenized and photoaffinity labeled by incubation with 1 microM 32P-labeled 8-azido-adenosine 3',5'-cyclic monophosphate (N3-8-(32P)-cAMP); the incorporated 32P was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Both in MCT and MTAL preparations, the analyses showed incorporation of N3-8-(32P)cAMP into two bands (Mr = 49,000 and Mr = 55,000) that comigrated with standards of the cAMP-dependent protein kinase regulatory subunits RI and RII. In MCT, most of the 32P (80%) was incorporated into RI, whereas in MTAL the 32P incorporated into RI and RII was equivalent. When freshly dissected MCT segments were incubated with 10(-12)-10(-6) M AVP, the subsequent photoaffinity labeling of RI with N3-8-(32P)cAMP was markedly diminished in a dose-dependent manner compared with controls. Our results suggest that cAMP binds in MCT and MTAL to regulatory subunits RI and RII of cAMP-dependent protein kinase. However, in MCT the dominant type of cAMP-dependent protein kinase appears to be type I. The outlined procedure is suitable to indirectly measure the occupancy of RI by endogenous cAMP generated in MCT cells in response to physiological levels (10(-12) M) of AVP.

  11. Intrasteric control of AMPK via the gamma1 subunit AMP allosteric regulatory site. (United States)

    Adams, Julian; Chen, Zhi-Ping; Van Denderen, Bryce J W; Morton, Craig J; Parker, Michael W; Witters, Lee A; Stapleton, David; Kemp, Bruce E


    AMP-activated protein kinase (AMPK) is a alphabetagamma heterotrimer that is activated in response to both hormones and intracellular metabolic stress signals. AMPK is regulated by phosphorylation on the alpha subunit and by AMP allosteric control previously thought to be mediated by both alpha and gamma subunits. Here we present evidence that adjacent gamma subunit pairs of CBS repeat sequences (after Cystathionine Beta Synthase) form an AMP binding site related to, but distinct from the classical AMP binding site in phosphorylase, that can also bind ATP. The AMP binding site of the gamma(1) CBS1/CBS2 pair, modeled on the structures of the CBS sequences present in the inosine monophosphate dehydrogenase crystal structure, contains three arginine residues 70, 152, and 171 and His151. The yeast gamma homolog, snf4 contains a His151Gly substitution, and when this is introduced into gamma(1), AMP allosteric control is substantially lost and explains why the yeast snf1p/snf4p complex is insensitive to AMP. Arg70 in gamma(1) corresponds to the site of mutation in human gamma(2) and pig gamma(3) genes previously identified to cause an unusual cardiac phenotype and glycogen storage disease, respectively. Mutation of any of AMP binding site Arg residues to Gln substantially abolishes AMP allosteric control in expressed AMPK holoenzyme. The Arg/Gln mutations also suppress the previously described inhibitory properties of ATP and render the enzyme constitutively active. We propose that ATP acts as an intrasteric inhibitor by bridging the alpha and gamma subunits and that AMP functions to derepress AMPK activity.

  12. cAMP prevents TNF-induced apoptosis through inhibiting DISC complex formation in rat hepatocytes. (United States)

    Bhattacharjee, Rajesh; Xiang, Wenpei; Wang, Yinna; Zhang, Xiaoying; Billiar, Timothy R


    Tumor necrosis factor α (TNF) is a pleiotropic proinflammatory cytokine that plays a role in immunity and the control of cell proliferation, cell differentiation, and apoptosis. The pleiotropic nature of TNF is due to the formation of different signaling complexes upon the binding of TNF to its receptor, TNF receptor type 1 (TNFR1). TNF induces apoptosis in various mammalian cells when the cells are co-treated with a transcription inhibitor like actinomycin D (ActD). When TNFR1 is activated, it recruits an adaptor protein, TNF receptor-associated protein with death domain (TRADD), through its cytoplasmic death effector domain (DED). TRADD, in turn, recruits other signaling proteins, including TNF receptor-associated protein 2 (TRAF2) and receptor-associated protein kinase (RIPK) 1, to form a complex. Subsequently, this complex combines with FADD and procaspase-8, converts into a death-inducing signaling complex (DISC) to induce apoptosis. Cyclic AMP (cAMP) is a second messenger that regulates various cellular processes such as cell proliferation, gene expression, and apoptosis. cAMP analogues are reported to act as anti-apoptotic agents in various cell types, including hepatocytes. We found that a cAMP analogue, dibutyryl cAMP (db-cAMP), inhibits TNF+ActD-induced apoptosis in rat hepatocytes. The protein kinase A (PKA) inhibitor KT-5720 reverses this inhibitory effect of cAMP on apoptosis. Cytoprotection by cAMP involves down-regulation of various apoptotic signal regulators like TRADD and FADD and inhibition of caspase-8 and caspase-3 cleavage. We also found that cAMP exerts its affect at the proximal level of TNF signaling by inhibiting the formation of the DISC complex upon the binding of TNF to TNFR1. In conclusion, our study shows that cAMP prevents TNF+ActD-induced apoptosis in rat hepatocytes by inhibiting DISC complex formation.

  13. Evidences for involvement of endogenous cAMP in Arabidopsis defense responses to Verticillium toxins

    Institute of Scientific and Technical Information of China (English)

    Jing JIANG; Ling Wen FAN; Wei Hua WU


    Although there were reports suggesting the involvement of endogenous cAMP in plant defense signaling cascades,there is no direct evidence supporting this notion yet and the detailed mechanism is unclear. In the present study, we have used pathogenic fungi Verticillium dahliae and Arabidopsis plants as a model system of plant-microb interaction to demonstrate the function of endogenous cAMP in Arabidopsis defense responses. Both V. dahliae inoculation and Verticillium toxins injection induced typical "wilt" symptoms in Arabidopsis seedlings. When either 8-Br-AMP (a membrane permeable cAMP analogue) or salicylic acid (SA) was applied to Arabidopsis, the plants became resistant to V. dahliae toxins. However, addition of 8-Br-AMP did not increase the resistance of Arabidopsis transgenic plants deficient in SA to the toxins, suggesting that cAMP might act upstream of SA in plant defense signaling pathway.Indeed, 8-Br-cAMP and forskolin, an activator of adenylyl cyclase, significantly stimulated the endogenous SA level in plants, whereas DDA, an inhibitor of adenylyl cyclase dramatically reduced toxin-induced SA increase. Both the endogenous cAMP and SA increased significantly in Arabidopsis seedlings treated with toxins. Furthermore, transcription level of pathogenesis-related protein 1 gene (PR1) was strongly induced by both 8-Br-cAMP and the toxin treatment. Taken together, our data demonstrate that endogenous cAMP is involved in plant defense responses against Verticilliumsecreted toxins by regulating the production of the known signal SA in plant defense pathway.

  14. PKA and Epac activation mediates cAMP-induced vasorelaxation by increasing endothelial NO production. (United States)

    García-Morales, Verónica; Cuíñas, Andrea; Elíes, Jacobo; Campos-Toimil, Manuel


    Vascular relaxation induced by 3',5'-cyclic adenosine monophosphate (cAMP) is both endothelium-dependent and endothelium-independent, although the underlying signaling pathways are not fully understood. Aiming to uncover potential mechanisms, we performed contraction-relaxation experiments on endothelium-denuded and intact rat aorta rings and measured NO levels in isolated human endothelial cells using single cell fluorescence imaging. The vasorelaxant effect of forskolin, an adenylyl cyclase activator, was decreased after selective inhibitor of protein kinase A (PKA), a cAMP-activated kinase, or L-NAME, an endothelial nitric oxide synthase (eNOS) inhibitor, only in intact aortic rings. Both selective activation of PKA with 6-Bnz-cAMP and exchange protein directly activated by cAMP (Epac) with 8-pCPT-2'-O-Me-cAMP significantly relaxed phenylephrine-induced contractions. The vasorelaxant effect of the Epac activator, but not that of the PKA activator, was reduced by endothelium removal. Forskolin, dibutyryl cAMP (a cAMP analogue), 6-Bnz-cAMP and 8-pCPT-2'-O-Me-cAMP increased NO levels in endothelial cells and the forskolin effect was significantly inhibited by inactivation of both Epac and PKA, and eNOS inhibition. Our results indicate that the endothelium-dependent component of forskolin/cAMP-induced vasorelaxation is partially mediated by an increase in endothelial NO release due to an enhanced eNOS activity through PKA and Epac activation in endothelial cells.

  15. Dibutyryl cAMP effects on thromboxane and leukotriene production in decompression-induced lung injury (United States)

    Little, T. M.; Butler, B. D.


    Decompression-induced venous bubble formation has been linked to increased neutrophil counts, endothelial cell injury, release of vasoactive eicosanoids, and increased vascular membrane permeability. These actions may account for inflammatory responses and edema formation. Increasing the intracellular cAMP has been shown to decrease eicosanoid production and edema formation in various models of lung injury. Reduction of decompression-induced inflammatory responses was evaluated in decompressed rats pretreated with saline (controls) or dibutyryl cAMP (DBcAMP, an analog of cAMP). After pretreatment, rats were exposed to either 616 kPa for 120 min or 683 kPa for 60 min. The observed increases in extravascular lung water ratios (pulmonary edema), bronchoalveolar lavage, and pleural protein in the saline control group (683 kPa) were not evident with DBcAMP treatment. DBcAMP pretreatment effects were also seen with the white blood cell counts and the percent of neutrophils in the bronchoalveolar lavage. Urinary levels of thromboxane B2, 11-dehydrothromboxane B2, and leukotriene E4 were significantly increased with the 683 kPa saline control decompression exposure. DBcAMP reduced the decompression-induced leukotriene E4 production in the urine. Plasma levels of thromboxane B2, 11-dehydrothromboxane B2, and leukotriene E4 were increased with the 683-kPa exposure groups. DBcAMP treatment did not affect these changes. The 11-dehydrothromboxane B2 and leukotriene E4 levels in the bronchoalveolar lavage were increased with the 683 kPa exposure and were reduced with the DBcAMP treatment. Our results indicate that DBcAMP has the capability to reduce eicosanoid production and limit membrane permeability and subsequent edema formation in rats experiencing decompression sickness.

  16. Heterogeneity of Calcium Channel/cAMP-Dependent Transcriptional Activation. (United States)

    Kobrinsky, Evgeny


    The major function of the voltage-gated calcium channels is to provide the Ca(2+) flux into the cell. L-type voltage-gated calcium channels (Cav1) serve as voltage sensors that couple membrane depolarization to many intracellular processes. Electrical activity in excitable cells affects gene expression through signaling pathways involved in the excitation-transcription (E-T) coupling. E-T coupling starts with activation of the Cav1 channel and results in initiation of the cAMP-response element binding protein (CREB)-dependent transcription. In this review we discuss the new quantitative approaches to measuring E-T signaling events. We describe the use of wavelet transform to detect heterogeneity of transcriptional activation in nuclei. Furthermore, we discuss the properties of discovered microdomains of nuclear signaling associated with the E-T coupling and the basis of the frequency-dependent transcriptional regulation.

  17. Functional modulation of AMP-activated protein kinase by cereblon. (United States)

    Lee, Kwang Min; Jo, Sooyeon; Kim, Hyunyoung; Lee, Jongwon; Park, Chul-Seung


    Mutations in cereblon (CRBN), a substrate binding component of the E3 ubiquitin ligase complex, cause a form of mental retardation in humans. However, the cellular proteins that interact with CRBN remain largely unknown. Here, we report that CRBN directly interacts with the α1 subunit of AMP-activated protein kinase (AMPK α1) and inhibits the activation of AMPK activation. The ectopic expression of CRBN reduces phosphorylation of AMPK α1 and, thus, inhibits the enzyme in a nutrient-independent manner. Moreover, AMPK α1 can be potently activated by suppressing endogenous CRBN using CRBN-specific small hairpin RNAs. Thus, CRBN may act as a negative modulator of the AMPK signaling pathway in vivo.

  18. Revascularisation of fresh compared with demineralised bone grafts in rats

    DEFF Research Database (Denmark)

    Solheim, E; Pinholt, E M; Talsnes, O


    Revascularisation of bone grafts is influenced by both the anatomical origin and the pre-implantation processing of the graft. We investigated the revascularisation by entrapment of 141Ce (cerium)-labelled microspheres in large, fresh and demineralised syngeneic grafts of predominantly cancellous...


    NARCIS (Netherlands)



    Collagen-based skin substitutes are among the most promising materials to improve regeneration of full-thickness wounds. However, additional meshed grafts or cultured epidermal grafts are still required to create epidermal regeneration. To avoid this, we substituted collagen-based split grafts, i.e.

  20. Superhydrophobic bio-fibre surfaces via tailored grafting architecture. (United States)

    Nyström, Daniel; Lindqvist, Josefina; Ostmark, Emma; Hult, Anders; Malmström, Eva


    Superhydrophobic bio-fibre surfaces with a micro-nano-binary surface structure have been achieved via the surface-confined grafting of glycidyl methacrylate, using a branched "graft-on-graft" architecture, followed by post-functionalisation to obtain fluorinated brushes.


    NARCIS (Netherlands)



    To evaluate the potential of a supporting, compliant, biodegradable prosthesis to function as a temporary protective scaffold for autologous vein grafts in the arterial circulation, we implanted vein grafts into the carotid arteries of rabbits, either with (composite grafts) or without (control graf

  2. 21 CFR 872.3930 - Bone grafting material. (United States)


    ...) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3930 Bone grafting material. (a) Identification... “Class II Special Controls Guidance Document: Dental Bone Grafting Material Devices.” (See § 872.1(e) for... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Bone grafting material. 872.3930 Section...

  3. Primary Adenocarcinoma in an Oesophageal Gastric Graft – Case Report

    Directory of Open Access Journals (Sweden)

    Dranka-Bojarowska Daria


    Full Text Available Primary adenocarcinoma in the esophageal gastric graft is a rare complication diagnosed in patients with long-term survival. Most data concerning the diagnosis and treatment of patients with metachronic cancer in esophageal grafts is derived from Japan and South Korea. The diagnosis of cancer in esophageal gastric grafts in the European countries is rare.

  4. Nucleic acid therapy for lifespan prolongation: Present and future

    Indian Academy of Sciences (India)

    Wing-Fu Lai


    Lifespan prolongation is a common desire of the human race. With advances in biotechnology, the mechanism of aging has been gradually unraveled, laying the theoretical basis of nucleic acid therapy for lifespan prolongation. Regretfully, clinically applicable interventions do not exist without the efforts of converting theory into action, and it is the latter that has been far from adequately addressed at the moment. This was demonstrated by a database search on PubMed and Web of Science, from which only seven studies published between 2000 and 2010 were found to directly touch on the development of nucleic acid therapy for anti-aging and/or longevity enhancing purposes. In light of this, the objective of this article is to overview the current understanding of the intimate association between genes and longevity, and to bring the prospect of nucleic acid therapy for lifespan prolongation to light.

  5. QT prolongation in a child with thyroid storm (United States)

    Albert, Benjamin B; Eckersley, Luke Gerard; Skinner, Jonathan Robert; Jefferies, Craig


    Summary A 12-year-old girl presented with an acute confusional state and a 2-year history of weight loss, anxiety, agitation and recurrent fever. Thyroid function tests confirmed severe hyperthyroidism, and a diagnosis of thyroid storm was made (Burch and Wartofsky score=75). ECG showed a prolonged QTc interval of 506 ms. Acute treatment for thyroid storm consisted of Lugol's iodine, prednisolone, carbimazole and propranolol. She made a steady recovery and by 3 months her thyroid function had normalised; a repeat ECG showed a QTc within the normal range (430 ms). There was no relevant family history. This is a case of QTc prolongation with hyperthyroidism and normalisation with euthyroidism. It is not commonly recognised that hyperthyroidism in children may be associated with QTc prolongation. QTc measurement should be incorporated into management protocols for hyperthyroidism. PMID:24729112

  6. Severe postpartum sepsis with prolonged myocardial dysfunction: a case report

    Directory of Open Access Journals (Sweden)

    Chen Katherine T


    Full Text Available Abstract Introduction Severe sepsis during pregnancy or in the postpartum period is a rare clinical event. In non obstetric surviving patients, the cardiovascular changes seen in sepsis and septic shock are fully reversible five to ten days after their onset. We report a case of septic myocardial dysfunction lasting longer than ten days. To the best of our knowledge, this is the first report of prolonged septic myocardial dysfunction in a parturient. Case presentation A 24 year old Hispanic woman with no previous medical history developed pyelonephritis and severe sepsis with prolonged myocardial dysfunction after a normal spontaneous vaginal delivery. Conclusions Septic myocardial dysfunction may be prolonged in parturients requiring longer term follow up and pharmacologic treatment.

  7. QTc-prolonging drugs and hospitalizations for cardiac arrhythmias

    DEFF Research Database (Denmark)

    De Bruin, Marie L; Hoes, Arno W; Leufkens, Hubert G M


    , and subsequently focused on several specific groups of patients who could be extremely vulnerable for drug-induced arrhythmias. We performed a case-control study in which patients (cases), hospitalized for nonatrial cardiac arrhythmias from 1987 to 1998, were compared with their matched controls regarding current...... use of QTc-prolonging drugs. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate conditional logistic regression, adjusting for potential confounding factors. Data were obtained from the PHARMO record linkage system. We identified 501 cases, 39 of whom used QTc......-prolonging drugs. A statistically nonsignificant increased risk for arrhythmias (OR 1.2, 95% CI 0.8 to 1.9) was observed in patients who received QTc-prolonging drugs. A clearly increased risk of arrhythmias was, however, found in patients with a history of asthma (OR 9.9, 95% CI 1.0 to 100) and in patients using...

  8. Left Ventricular Function After Prolonged Exercise in Equine Endurance Athletes

    DEFF Research Database (Denmark)

    Flethøj, M.; Schwarzwald, C. C.; Haugaard, M. M.


    and diastolic function in horses. Animals: Twenty-six horses competing in 120–160 km endurance rides. Methods: Cross-sectional field study. Echocardiography was performed before and after rides, and the following morning, and included two-dimensional echocardiography, anatomical M-mode, pulsed-wave tissue......Background: Prolonged exercise in human athletes is associated with transient impairment of left ventricular (LV) function, known as cardiac fatigue. Cardiac effects of prolonged exercise in horses remain unknown. Objectives :To investigate the effects of prolonged exercise on LV systolic...... function. Reduced ventricular filling persisted for 7–21 hours despite normalization of biochemical indicators of hydration status, indicating that the observed changes were not entirely related to altered preload conditions. The clinical relevance of cardiac fatigue in horses remains uncertain....

  9. Prolongation of liver allograft survival by dendritic cells modified with NF-κB decoy oligodeoxynucleotides

    Institute of Scientific and Technical Information of China (English)

    Ming-Qing Xu; Yu-Ping Suo; Jian-Ping Gong; Ming-Man Zhang; Lü-Nan Yan


    significant allocostimulatory activity. NF-κB decoy ODNs completely abrogated IL-4-induced DC maturation and allocostimulatory activity as well as LPS-induced NF-κB activation and IL-12protein expression in DCs. GM-CSF+NF-κB decoy ODNspropagated DCs promoted apoptosis of liver allograftinfiltrating cells within portal areas, and significantly decreased the expression of IL-2 and IFN-γ mRNA but markedly elevated IL-4 mRNA expression both in liver allograft and in recipient spleen, and consequently suppressed liver allograft rejection, and promoted liver allograft survival.CONCLUSION: NF-κB decoy ODNs-modified DCs can prolong liver allograft survival by promoting apoptosis of graft-infiltrating cells within portal areas as well as downregulating IL-2 and IFN-γ mRNA and up-regulating IL-4 mRNA expression both in liver graft and in recipient spleen.

  10. Preparation and Mechanical Properties of Solid-phase Grafting Nanocomposites of PVC/Graft Copolymers/MMT

    Institute of Scientific and Technical Information of China (English)

    ZHOU Dunbai; CAI Changgen; JIA Demin


    In order to improve the mechanical properties of PVC, by solid-phase grafting reaction, grafting on and nano-modifying the PVC process synchronously, acrylic monomers not only graft on PVC, but also are intercalated into the layers of MMT in the heating process. Blending PVC and the MMT-PVC grafting copolymers, we can get nanocomposites of PVC/ grafters/ MMT, and the mechanical performance of the material is improved.

  11. Complications in skin grafts when continuing antithrombotic therapy prior to cutaneous surgery requiring skin grafting

    DEFF Research Database (Denmark)

    Jarjis, Reem Dina; Jørgensen, Lone; Finnerup, Kenneth


    studies were of prospective and retrospective design. Most of the reviewed studies suggest that the use of antithrombotic therapy can increase the risk of bleeding complications in skin grafts. These complications are only wound threatening and not life threatening. Therefore, this is of concern mostly...... in terms of hemostasis by the surgeon and good pressure dressings. Care should be taken when operating on anticoagulated patients undergoing cutaneous surgery requiring skin grafting. However, graft failure is rare and, given the risk of thrombotic events, the reviewed studies recommend continuing all......Abstract The risk of postoperative bleeding and wound healing complications in skin grafts among anticoagulated patients undergoing cutaneous surgery has not been firmly established. The objective was to examine the literature and assess the risk of postoperative bleeding or wound healing...

  12. Prolonged nerve blockade in a patient treated with lithium

    Directory of Open Access Journals (Sweden)

    Lehavi A


    Full Text Available Amit Lehavi, Boris Shenderey, Yeshayahu (Shai KatzDepartment of Anesthesiology, Rambam Health Care Campus, Haifa, IsraelAbstract: We report a case of a patient, chronically treated with oral lithium, who presented with an extremely prolonged (42-hour duration of sensory and motor paralysis following an uneventful infraclavicular block for hand surgery that was performed under ultrasound guidance using bupivacaine and lidocaine. Due to its direct effect on nerve conduction of action potential, we propose that lithium may have had a role in the unusually prolonged duration of a peripheral nerve block.Keywords: nerve blockade, lithium, duration, anesthesia

  13. Bartonella henselae Infective Endocarditis Detected by a Prolonged Blood Culture (United States)

    Mito, Tsutomu; Hirota, Yusuke; Suzuki, Shingo; Noda, Kazutaka; Uehara, Takanori; Ohira, Yoshiyuki; Ikusaka, Masatomi


    A 65-year-old Japanese man was admitted with a 4-month history of fatigue and exertional dyspnea. Transthoracic echocardiography revealed a vegetation on the aortic valve and severe aortic regurgitation. Accordingly, infective endocarditis and heart failure were diagnosed. Although a blood culture was negative on day 7 after admission, a prolonged blood culture with subculture was performed according to the patient's history of contact with cats. Consequently, Bartonella henselae was isolated. Bartonella species are fastidious bacteria that cause blood culture-negative infective endocarditis. This case demonstrates that B. henselae may be detected by prolonged incubation of blood cultures. PMID:27746451

  14. Changes in the human blood coagulating system during prolonged hypokinesia (United States)

    Filatova, L. M.; Anashkin, O. D.


    Changes in the coagulating system of the blood were studied in six subjects during prolonged hypokinesia. Thrombogenic properties of the blood rose in all cases on the 8th day. These changes are explained by stress reaction due to unusual conditions for a healthy person. Changes in the blood coagulating system in the group subjected to physical exercise and without it ran a practically parallel course. Apparently physical exercise is insufficient to prevent such changes that appear in the coagulating system of the blood during prolonged hypokinesia.

  15. Sponsored parachute jumps--can they cause prolonged pain?


    Straiton, N; Sterland, J


    A survey of parachute injuries sustained in 1984 at a local parachute club was made using hospital notes and a questionnaire. The overall injury rate was 0.2%. The injury rate in first time jumpers was 1.1%. The injuries often resulted in a prolonged hospital stay, time off work and residual pain and disability. Injury rates may be reduced by more prolonged and intensive training preceding the first jumps. Those people not interested in parachuting as a regular sport and who jump once only in...

  16. Sponsored parachute jumps--can they cause prolonged pain? (United States)

    Straiton, N; Sterland, J


    A survey of parachute injuries sustained in 1984 at a local parachute club was made using hospital notes and a questionnaire. The overall injury rate was 0.2%. The injury rate in first time jumpers was 1.1%. The injuries often resulted in a prolonged hospital stay, time off work and residual pain and disability. Injury rates may be reduced by more prolonged and intensive training preceding the first jumps. Those people not interested in parachuting as a regular sport and who jump once only in order to raise money for charity are at risk of serious injury and perhaps should consider less dangerous alternatives.

  17. Hypoglycaemia and QT interval prolongation in type 1 diabetes

    DEFF Research Database (Denmark)

    Christensen, Toke Folke; Cichosz, Simon Lebech; Tarnow, L.


    hypoglycaemia varies greatly between studies. METHODS: We studied ten adults with type 1 diabetes (age 41±15years) without cardiovascular disease or neuropathy. Single-blinded hypoglycaemia was induced by a subcutaneous insulin bolus followed by a control episode on two occasions separated by 4weeks. QT....... CONCLUSIONS: Hypoglycaemia as experienced after a subcutaneous injection of insulin may cause QTc prolongation in type 1 diabetes. However, the magnitude of prolongation is less than typically reported during glucose clamp studies, possible because of the study design with focus on minimizing unwanted study...

  18. Atrazine acts as an endocrine disrupter by inhibiting cAMP-specific phosphodiesterase-4

    Energy Technology Data Exchange (ETDEWEB)

    Kucka, Marek [Section on Cellular Signaling, Program in Developmental Neuroscience, NICHD, NIH, Bethesda, MD (United States); Pogrmic-Majkic, Kristina; Fa, Svetlana [Laboratory for Ecotoxicology, Department of Biology and Ecology, University of Novi Sad, Faculty of Sciences, 21000 Novi Sad (Serbia); Stojilkovic, Stanko S. [Section on Cellular Signaling, Program in Developmental Neuroscience, NICHD, NIH, Bethesda, MD (United States); Kovacevic, Radmila, E-mail: [Laboratory for Ecotoxicology, Department of Biology and Ecology, University of Novi Sad, Faculty of Sciences, 21000 Novi Sad (Serbia)


    Atrazine, one of the most commonly used herbicides worldwide, acts as an endocrine disruptor, but the mechanism of its action has not been characterized. In this study, we show that atrazine rapidly increases cAMP levels in cultured rat pituitary and testicular Leydig cells in a concentration-dependent manner, but less effectively than 3-isobutyl-1-methylxanthine, a competitive non-specific inhibitor of phosphodiesterases (PDEs). In forskolin (an activator of adenylyl cyclase)- and probenecid (an inhibitor of cyclic nucleotide transporters)-treated cells, but not in 3-isobutyl-1-methylxanthine-treated cells, atrazine further increased cAMP levels, indicating that inhibition of PDEs accounts for accumulation of cAMP. In contrast to cAMP, atrazine did not alter cGMP levels, further indicating that it inhibits cAMP-specific PDEs. Atrazine-induced changes in cAMP levels were sufficient to stimulate prolactin release in pituitary cells and androgen production in Leydig cells, indicating that it acts as an endocrine disrupter both in cells that secrete by exocytosis of prestored hormones and in cells that secrete by de novo hormone synthesis. Rolipram abolished the stimulatory effect of atrazine on cAMP release in both cell types, suggesting that it acts as an inhibitor of PDE4s, isoforms whose mRNA transcripts dominate in pituitary and Leydig cells together with mRNA for PDE8A. In contrast, immortalized lacto-somatotrophs showed low expression of these mRNA transcripts and several fold higher cAMP levels compared to normal pituitary cells, and atrazine was unable to further increase cAMP levels. These results indicate that atrazine acts as a general endocrine disrupter by inhibiting cAMP-specific PDE4s. -- Highlights: ► Atrazine stimulates cAMP accumulation in pituitary and Leydig cells. ► Atrazine also stimulates PRL and androgens secretion. ► Stimulatory effects of atrazine were abolished in cells with IBMX-inhibited PDEs. ► Atrazine specificity toward cAMP

  19. A decision tree for soft tissue grafting. (United States)

    Leong, Daylene Jack-Min; Wang, Hom-Lay


    Periodontal plastic surgery is commonly performed for esthetic and physiologic reasons, such as alleviating root sensitivity, root caries, and cervical abrasion and facilitating plaque control at the affected site. Currently, there is a lack of information regarding the most appropriate treatment method for the various clinical situations encountered. The aims of this paper are to review and discuss the various clinical situations that require soft tissue grafting and to attempt to provide recommendations for the most predictable technique. Using MEDLINE and The Cochrane Library, a review of all available literature was performed. Papers published in peer-reviewed journals written in English were chosen and reviewed to validate the decision-making process when planning for soft tissue grafting. A decision tree was subsequently developed to guide clinicians to choose the most appropriate soft tissue grafting procedure by taking into consideration the following clinical parameters: etiology, purpose of the procedure, adjacent interproximal bone level, and overlying tissue thickness. The decision tree proposed serves as a guide for clinicians to select the most appropriate and predictable soft tissue grafting procedure to minimize unnecessary mistakes while providing the ultimate desired treatment outcome.

  20. Tissue Engineering: Creating Living Cardiovascular Grafts

    NARCIS (Netherlands)

    Muylaert, D.E.P.


    When heart valves or coronary arteries fail, the surgical implantation of a replacement structure can be a life-saving operation. Right now, replacement vessels for bypass grafting are harvested from the leg or chest of the patient, which is an additional and invasive procedure. Similarly, heart val

  1. Polyethylene glycol-grafted polystyrene particles

    NARCIS (Netherlands)

    Meng, Fenghua; Engbers, Gerard H.M.; Feijen, Jan


    Densely pegylated particles that can serve as a model system for artificial cells were prepared by covalently grafting amino polyethylene glycol (PEG, molecular weight 3400 or 5000) onto carboxyl polystyrene particles (PS-COOH) using carbodiimide chemistry. PEG-modified particles (PS-PEG) were chara

  2. Endothelialized ePTFE Graft by Nanobiotechnology (United States)


    The Apparatus for Processing the Tubular Graft Modification Will be Designed and Evaluated.; The On-site Capturing of the Endothelial (Progenitor) Cells by Peptide-mediated Selective Adhesion in Vitro and in Vivo Will Also be Elucidated.; The Patency Rate of ITRI-made Artificial Blood Vessels Will be Evaluated by the Porcine Animal Model.

  3. Cellular grafts in management of leucoderma

    Directory of Open Access Journals (Sweden)

    Mysore Venkataram


    Full Text Available Cellular grafting methods constitute important advances in the surgical management of leucoderma. Different methods such as noncultured epidermal suspensions, melanocyte cultures, and melanocyte-keratinocyte cultures have all been shown to be effective. This article reviews these methods.

  4. Grafted silane monolayers: reconsideration of growth mechanisms (United States)

    Ivanov, D. A.; Nysten, B.; Jonas, A. M.; Legras, R.


    Chemical force microscopy is a new technique devised to image chemical heterogeneities on surfaces. It requires the chemical modification of Atomic Force Microscopy (AFM) tips in order to create chemical probes. In this respect, self-assembled monolayers (SAM) of alkylchlorosilanes are particularly interesting as modifying agents for AFM tips. We report here our results on the kinetics of silanization and on the structure of such SAM's grafted on model surfaces (hydroxylated Si(100) wafers). AFM, contact angle measurements, X-ray reflectivity and X-ray photoelectron spectroscopy were used to characterize SAM's of octadecyltrichlorosilane (OTS) and octadecyldimethylchlorosilane (ODMS) grown from hexadecane and toluene solutions. The mechanism of grafting of OTS follows two stages. The first rapid stage corresponds to the nucleation and growth of island-like monolayer domains. The second slower stage is related to the densification of the monolayer. SAM's of ODMS were found to form thinner layers as compared to OTS, due to their lower grafting density probably resulting in a more disordered state of grafted alkyl chains. We also address the problems concerning the relationships between the quality of final SAM structures and the water content as well as the nature of the solvent used for silanization.

  5. Naevus depiomentosus treated with suction blister grafting

    Directory of Open Access Journals (Sweden)

    Ravikumar B


    Full Text Available Naevus depigmentosus is a congenital hypomelanotic condition in which the off white lesions are permanent and cosmetically embarassing. There has been no effective treatment reported so for for this condition. Here we are reporting a patient of naevus depigmentosus on whom we performed suction blister grafting and the resultant pigmentation was satisfactory

  6. Dynamics of solvent-free grafted nanoparticles

    KAUST Repository

    Chremos, Alexandros


    The diffusivity and structural relaxation characteristics of oligomer-grafted nanoparticles have been investigated with simulations of a previously proposed coarse-grained model at atmospheric pressure. Solvent-free, polymer-grafted nanoparticles as well as grafted nanoparticles in a melt were compared to a reference system of bare (ungrafted) particles in a melt. Whereas longer chains lead to a larger hydrodynamic radius and lower relative diffusivity for grafted particles in a melt, bulk solvent-free nanoparticles with longer chains have higher relative diffusivities than their short chain counterparts. Solvent-free nanoparticles with short chains undergo a glass transition as indicated by a vanishing diffusivity, diverging structural relaxation time and the formation of body-centered-cubic-like order. Nanoparticles with longer chains exhibit a more gradual increase in the structural relaxation time with decreasing temperature and concomitantly increasing particle volume fraction. The diffusivity of the long chain nanoparticles exhibits a minimum at an intermediate temperature and volume fraction where the polymer brushes of neighboring particles overlap, but must stretch to fill the interparticle space. © 2012 American Institute of Physics.

  7. Femoral revision surgery with impaction bone grafting

    NARCIS (Netherlands)

    B.L.E.F. ten Have (Bas); R.W. Brouwer (Reinoud); F.C. van Biezen (Frans); J.A.N. Verhaar (Jan)


    textabstractThe purpose of this prospective study was to evaluate the long-term clinical and radiological outcomes of revision of the femoral component of a total hip replacement using impaction bone grafting. Femoral revision with an impacted allograft was performed on 29 patients (31 hips). In all

  8. Experimental vascular graft for liver transplantation

    NARCIS (Netherlands)

    Kobori, L; Nemeth, T; Nemes, B; Dallos, G; Sotonyi, P; Fehervari, [No Value; Patonai, A; Slooff, MJH; Jaray, J; De Jong, KP


    Hepatic artery thrombosis is a major cause of graft failure in liver transplantation. Use of donor interponates are common, but results are controversial because of necrosis or thrombosis after rejection. Reperfusion injury, hypoxia and free radical production determinate the survival. The aim of th

  9. Surface Grafting of Thermoresponsive Microgel Nanoparticles (Postprint) (United States)


    particles, made of temperature- responsive polymers, have been widely researched for carrying out separations, as substrates for bioreactors, for enzyme ...Corporation (Model PDC-32G) plasma cleaner /sterilizer was used in the current study to treat PVDF fibers and tungsten wires prior to the grafting. To

  10. Fatal Saccharomyces Cerevisiae Aortic Graft Infection (United States)

    Meyer, Michael (Technical Monitor); Smith, Davey; Metzgar, David; Wills, Christopher; Fierer, Joshua


    Saccharomyces cerevisiae is a yeast commonly used in baking and a frequent colonizer of human mucosal surfaces. It is considered relatively nonpathogenic in immunocompetent adults. We present a case of S. cerevisiae fungemia and aortic graft infection in an immunocompetent adult. This is the first reported case of S. cerevisiue fungemia where the identity of the pathogen was confirmed by rRNA sequencing.

  11. Skin flaps and grafts - self-care (United States)

    ... Regional flaps - self-care; Distant flaps - self-care; Free flap - self-care; Skin autografting - self-care; Pressure ulcer ... your wound To care for the graft or flap site: You may need to rest ... around it clean and free from dirt or sweat. DO NOT let the ...

  12. Reverse relationship between malignancy and cyclic AMP-dependent protein kinase activity in Yoshida rat ascites hepatomas. (United States)

    Miyamoto, K; Nakamura, S; Nomura, M; Yamamoto, H; Sanae, F; Hidaka, H


    Rat ascites hepatoma (AH) cells (10(6) cells/head) inoculated intraperitoneally into rats had host-killing ability (malignancy) in the order AH66F > AH44 > AH13 > AH7974 > AH109A > AH66 > AH130. The life span of the rats after inoculation closely correlated with the activity of cyclic AMP-dependent protein kinase (protein kinase A) in the tumor cells but not the activity of Ca2+/phospholipid-dependent protein kinase (protein kinase C). N-[2-[N-[3-(4-chlorophenyl)-1-methyl-2-propenyl]amino]ethyl]-5- isoquinoline-sulfonamide (H-87), a potent, selective inhibitor of protein kinase A, inhibited in vitro growth of these hepatoma cells with a similar potency and, intraperitoneally injected, prolonged the lives of rats bearing less malignant AH66 cells (with high protein kinase A activity) but did not affect the life span of rats bearing highly malignant AH66F cells (with low protein kinase A activity). On the other hand N-(2-methylpiperazyl)-5-isoquinolinesulfonamide (H-7), an inhibitor of protein kinase C, inhibited AH66F cells more than AH66 cells, but did not influence the life span of rats bearing either hepatoma. From these results it is deduced that protein kinase A may be important in the regulation of malignancy and in vivo proliferation of AH cells.

  13. Nasal bone grafts from the removed hump used as overlay grafts to camouflage concave lateral crura. (United States)

    Kubilay, Utku; Erdogdu, Suleyman; Sezen, Ozan Seymen


    Alar cartilage consists of a medial crus, middle crus and lateral crus. The lateral crus is an important aesthetic and functional structure of the nose. A 32-year-old male patient with concave lateral crura was operated by the authors. An open rhinoplasty with a dorsal approach to the septum is preferred. The nasal bones harvested from the hump, which is an autogenous graft trimmed and sutured on both concave lateral crura as an overlay camouflage grafts. Satisfactory result was achieved.

  14. Local full-thickness skin graft of the donor arm--a novel technique for the reduction of donor site morbidity in radial forearm free flap. (United States)

    Riecke, B; Assaf, A T; Heiland, M; Al-Dam, A; Gröbe, A; Blessmann, M; Wikner, J


    A novel technique to reduce donor site morbidity after radial forearm free flap (RFFF) harvest, using a local full-thickness skin graft (FTSG), is described. Thirty consecutive patients undergoing RFFF for head and neck reconstruction were enrolled in a prospective study. Donor site defect closure was performed with spindle-shaped FTSGs excised from the wavelike skin incision made for the vascular pedicle. Both the removal site of the FTSG on the volar forearm and the covered RFFF donor site healed uneventfully in 29 cases, with no impairment of function related to the skin graft. No skin graft failure and no exposure, tenting, or adherence of the flexor tendons occurred. All patients expressed satisfaction with postoperative pain, the functional outcome, and cosmetic appearance. Primary donor site defect closure could be achieved in all cases with the use of a local FTSG. This graft can be gained at the access incision for the vascular pedicle, avoids expansion of the incision for a local flap technique, and does not prolong wound healing, and thus reduces both donor site and graft site morbidity of the RFFF. This technique leads to an inconspicuous aesthetic result with no apparent relevant functional deficits and avoids the need for a second donor site.

  15. Infrarenal abdominal aortic aneurysm. Endovascular repair with stent grafts; Infrarenales Bauchaortenaneurysma. Endovaskulaere Stent-Graft-Therapie

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, M.; Voshage, G.; Landwehr, P. [Klinik fuer Diagnostische und Interventionelle Radiologie, Gefaesszentrum Hannover, Diakoniekrankenhaus Henriettenstiftung gGmbH, Hannover (Germany); Busch, T. [Klinik fuer Gefaesschirurgie, Gefaesszentrum Hannover, Diakoniekrankenhaus Henriettenstiftung gGmbH, Hannover (Germany)


    As an alternative to surgery, endovascular therapy with stent grafts has become the second main treatment option for infrarenal abdominal aortic aneurysms. Unlike surgery, endovascular treatment with stent grafts is also applicable in patients unfit for open repair. Despite current improvements in endovascular repair devices, significant anatomic barriers still exclude this technique for a large number of patients. Computed tomography, magnetic resonance imaging, and ultrasound are essential for diagnostics, preintervention planning, and postintervention follow-up of abdominal aneurysms treated with stent grafts. This review covers etiology, pathology, and diagnostic aspects. Materials and methods for endovascular treatment of abdominal aortic aneurysms are presented in detail, and clinical results and complications are discussed. (orig.) [German] Die endovaskulaere Therapie des infrarenalen Bauchaortenaneurysmas hat sich als Alternative zur offenen chirurgischen Versorgung etabliert. Im Gegensatz zu Letzterer ist die Aneurysmatherapie mittels Stent-Grafts auch bei schwerkranken, nicht operationsfaehigen Patienten moeglich, wobei der Nutzen kontrovers diskutiert wird. Im Gegensatz zur klassischen transabdominellen Operation ist die Stent-Graft-Technik anatomischen Einschraenkungen unterworfen, die aber kuenftig aufgrund bereits abzusehender technischer Weiterentwicklungen eine geringere Rolle spielen werden. Die Diagnostik, die Entscheidung fuer eine endovaskulaere Therapie, die praeinterventionelle Planung und die Nachsorge erfordern den Einsatz bildgebender Verfahren, v. a. der Computer- und Magnetresonanztomographie sowie der Sonographie. Die fuer die endovaskulaere Aneurysmabehandlung relevanten Aspekte der Diagnostik werden dargestellt. Auf die Technik, die Materialien, die Ergebnisse und die Komplikationen der Stent-Graft-Behandlung wird ausfuehrlich eingegangen. (orig.)

  16. Modulation of graft architectures for enhancing hydrophobic interaction of biomolecules with thermoresponsive polymer-grafted surfaces. (United States)

    Idota, Naokazu; Kikuchi, Akihiko; Kobayashi, Jun; Sakai, Kiyotaka; Okano, Teruo


    This paper describes the effects of graft architecture of poly(N-isopropylacrylamide) (PIPAAm) brush surfaces on thermoresponsive aqueous wettability changes and the temperature-dependent hydrophobic interaction of steroids in silica capillaries (I.D.: 50 μm). PIPAAm brushes were grafted onto glass substrates by surface-initiated atom transfer radical polymerization (ATRP) that is one of the living radical polymerization techniques. Increases in the graft density and chain length of PIPAAm brushes increased the hydration of polymer brushes, resulting in the increased hydrophilic properties of the surface below the transition temperature of PIPAAm at 32 °C. More hydrophobic surface properties were also observed on surfaces modified with the block copolymers of IPAAm and n-butyl methacrylate (BMA) than that with IPAAm homopolymer-grafted surfaces over the transition temperature. Using PBMA-b-PIPAAm-grafted silica capillaries, the baseline separation of steroids was successfully achieved by only changing temperature. The incorporation of hydrophobic PBMA chains in grafted PIPAAm enhanced the hydrophobic interaction with testosterone above the transition temperature. The surface modification of hydrophobicity-enhanced thermoresponsive polymers is a promising method for the preparation of thermoresponsive biointerfaces that can effectively modulated their biomolecule and cell adsorption with the wide dynamic range of hydrophilic/hydrophobic property change across the transition temperature.

  17. Numerical Simulation of Coronary Artery Bypass Graft with an Assistant Graft

    Institute of Scientific and Technical Information of China (English)

    WANG Wei; WANG Feng


    The conventional bypass design is to implant a graft on the stenosed host artery allowing blood to flow bypass the stenotic artery. However, restenosis is a challenging problem which finally results in reoperation. The purpose of this paper is to propose a new bypass graft design of coronary artery with an assistant graft for the treatment of coronary artery stenosis. An additional assistant graft was employed in the new design compared with the conventional ETS anastomosis. Numerical simulations were performed by means of finite volume method using computational fluid dynamics (CFD) solver. Results demonstrated that the new anastomoses model provided a more smooth flow at the distal ETS anastomosis without any stagnation point on anastomotic bed and vortex formation in the heel region. Oscillatory shear index (OSI) and time-averaged wall shear stress gradient (TAWSSG) at the artery bed of the distal ETS anastomosis were reduced. The coronary artery bypass graft with an assistant graft is feasible to improve the local hemodynamics and diminish the probability of restenosis in the treatment of coronary artery stenosis.

  18. Poly(amide-graft-acrylate) interfacial compounds (United States)

    Zamora, Michael Perez

    Graft copolymers with segments of dissimilar chemistries have been shown to be useful in a variety of applications as surfactants, compatibilizers, impact modifiers, and surface modifiers. The most common route to well defined graft copolymers is through the use of macromonomers, polymers containing a reactive functionality and thus capable of further polymerization. However, the majority of the studies thus far have focused on the synthesis of macromonomers capable of reacting with vinyl monomers to form graft copolymers. This study focused on the synthesis of macromonomers capable of participating in condensation polymerizations. A chain transfer functionalization method was utilized. Cysteine was evaluated as a chain transfer agent for the synthesis of amino acid functionalized poly(acrylate) and poly(methacrylate) macromonomers. Low molar mass, functionalized macromonomers were produced. These macromonomers were proven to be capable of reacting with amide precursors to form poly(amide-g-acrylate) graft copolymers. Macromonomers and graft copolymers were characterized by gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR) spectroscopy, elemental analysis (EA), inductively coupled plasma (ICP), and differential scanning calorimetry (DSC). The second part of this research involved poly(dimethacrylate) dental restorative materials. Volumetric shrinkage during the cure of these resins results in a poor interface between the resin and the remaining tooth structure, limiting the lifetime of these materials. Cyclic anhydrides were incorporated into common monomer compositions used in dental applications. Volume expansion from the ring opening hydrolysis of these anhydrides was shown to be feasible. The modified dental resins were characterized by swelling, extraction and ultraviolet spectroscopy (UV), and density measurements. Linear poLymers designed to model the crosslinked dental resins were

  19. Humidity Sensing Properties of Pre-irradiation Grafted HDPE Membranes

    Institute of Scientific and Technical Information of China (English)

    Zheng Jiao; Qun Fu; Xiang Geng; Zhen Li; Haijian Zhong


    Grafted high density polyethylene (HDPE) films have been prepared by grafting sodium styrene sulfonate (SSS) and acrylic acid (AA) onto HDPE using preirradiation method. The structure and surface morphology of both grafted and ungrafted HDPE films were observed by FTIR spectroscopy and scanning electron microscope (SEM), respectively. The humidity sensing properties of grafted HDPE films were investigated. The results show that the impedance of the film decreases with increasing of relative humidity (RH). The films display high sensitivity with nearly three orders of magnitude change in the resistance during the relative humidity variation from 5% to 98%. Grafted HDPE films exhibit excellent properties as humidity sensors.

  20. Stretch Polytetrafluoroethylene Grafts for Hemodialysis Angioaccess: Three-year Experience

    Directory of Open Access Journals (Sweden)

    Al Dayel Adel


    Full Text Available We report the results of 90 stretch polytetrafluoroethylene (PTFE grafts in 78 chronic renal failure patients over a 3-year period from 1995-1998. The grafts were used as primary access in 15% of the patients. The cumulative patency was 63.3% and there were no complications in 48.8% of the cases. Infection was encountered in 15.5% and thrombosis in 31.1% of the grafts. Intimal hyperplasia, venous anastomotic stenosis, improper puncture technique and subclavian vein stenosis were the major causes of failure of grafts. We conclude that stretch PTFE grafts as angioaccesses may provide good patency and durability.

  1. Evidence for cAMP as a mediator of gonadotropin secretion from male pituitaries

    Energy Technology Data Exchange (ETDEWEB)

    Bourne, G.A.; Baldwin, D.M.


    The purpose of this study was to use sodium flufenamate, a compound that inhibits gonadotropin-releasing hormone (GnRH)-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) production in the pituitary, to evaluate the potential role of cAMP as a mediator of GnRH-stimulated gonadotropin secretion from male pituitaries. Quartered male pituitaries were perifused at 37/sup 0/C and sequential effluent fractions collected every 10 min. Infusions of GnRH resulted in a twofold increase in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion. Cycloheximide, 5, completely inhibited the GnRH-stimulated LH and FSH secretion. Infusions of 0.1 mM flufenamate had similar effects on gonadotropin secretion as cycloheximide, whereas the administration of 5 mM dibutyryl cAMP in combination with GnRH and flufenamate restored the secretory responses of both hormones. The flufenamate-inhibited GnRH stimulated LH and FSH release, which was restored by DBcAMP and appeared to be protein synthesis dependent and specific for cAMP.These results suggest an indirect role for cAMP as a mediator of gonadotropin secretion from male pituitaries. However, in contrast to female pituitaries, the secretion of these hormones form male pituitaries is completely dependent on cAMP and de novo protein synthesis.

  2. Crystal structure of a c-di-AMP riboswitch reveals an internally pseudo-dimeric RNA. (United States)

    Jones, Christopher P; Ferré-D'Amaré, Adrian R


    Cyclic diadenosine monophosphate (c-di-AMP) is a second messenger that is essential for growth and homeostasis in bacteria. A recently discovered c-di-AMP-responsive riboswitch controls the expression of genes in a variety of bacteria, including important pathogens. To elucidate the molecular basis for specific binding of c-di-AMP by a gene-regulatory mRNA domain, we have determined the co-crystal structure of this riboswitch. Unexpectedly, the structure reveals an internally pseudo-symmetric RNA in which two similar three-helix-junction elements associate head-to-tail, creating a trough that cradles two c-di-AMP molecules making quasi-equivalent contacts with the riboswitch. The riboswitch selectively binds c-di-AMP and discriminates exquisitely against other cyclic dinucleotides, such as c-di-GMP and cyclic-AMP-GMP, via interactions with both the backbone and bases of its cognate second messenger. Small-angle X-ray scattering experiments indicate that global folding of the riboswitch is induced by the two bound cyclic dinucleotides, which bridge the two symmetric three-helix domains. This structural reorganization likely couples c-di-AMP binding to gene expression.

  3. Linking cellular actin status with cAMP signaling in Candida albicans. (United States)

    Wang, Yue; Zou, Hao; Fang, Hao-Ming; Zhu, Yong


    The fungal pathogen Candida albicans has a remarkable ability to switch growth forms. Particularly, the yeast-to-hyphae switch is closely linked with its virulence. A range of chemicals and conditions can promote hyphal growth including serum, peptidoglycan, CO2, neutral pH, and elevated temperature. All these signals act essentially through the adenylyl cyclase Cyr1 that synthesizes cAMP. Cells lacking Cyr1 are completely defective in hyphal growth. Recently, cellular actin status is found to influence cAMP synthesis. However, how Cyr1 senses and processes multiple external and internal signals to produce a contextually proper level of cAMP remains unclear. We hypothesized that Cyr1 itself possesses multiple sensors for different signals and achieves signal integration through a combined allosteric effect on the catalytic center. To test this hypothesis, we affinity-purified a Cyr1-containing complex and found that it could enhance cAMP synthesis upon treatment with serum, peptidoglycan or CO2 in vitro. The data indicate that the complex is an essentially intact sensor/effector apparatus for cAMP synthesis. The complex contains two more subunits, the cyclase-associated protein Cap1 and G-actin. We discovered that G-actin plays a regulatory role, rendering cAMP synthesis responsive to actin dynamics. These findings shed new lights on the mechanisms that regulate cAMP-mediated responses in fungi.

  4. Dopamine-induced cyclic AMP increase in canine myocardium, kidney and superior mesenteric artery.

    Directory of Open Access Journals (Sweden)



    Full Text Available The effect of dopamine on cyclic AMP levels in tissue slices of canine myocardium and kidney, and in chopped superior mesenteric arterial wall was investigated to identify dopamine receptors. Tissues were incubated in modified Krebs-Henseleit Ringer bicarbonate solution at 37 degrees C for 20 min with test drugs, after 20-min preincubation. In the presence of 3-isobutyl-1-methylxanthine (IBMX, dopamine and apomorphine caused dose-dependent increases in cyclic AMP levels in the myocardium, kidney and superior mesenteric artery. Phentolamine significantly intensified the cyclic AMP-increasing effect of dopamine in the superior mesenteric artery, but it did not influence the cyclic AMP increase caused by dopamine or apomorphine in the myocardium and kidney. Propranolol markedly blocked the effect of dopamine on cyclic AMP levels in all tissues studied. Haloperidol slightly inhibited the effect of dopamine and completely blocked the effect of apomorphine in the myocardium and kidney. These data suggest that dopamine increases cyclic AMP levels by activating predominantly beta-adrenergic receptors and partly dopamine receptors in the canine myocardium, kidney and superior mesenteric artery. The present results also suggest that dopamine acts not only on beta-adrenergic and dopamine receptors but also on alpha-adrenergic receptors in the superior mesenteric artery. Contrary to the activation of beta-adrenergic and dopamine receptors, the activation of alpha-adrenergic receptors resulted in a decrease in cyclic AMP levels in this tissue.

  5. Spatiotemporal coupling of cAMP transporter to CFTR chloride channel function in the gut epithelia. (United States)

    Li, Chunying; Krishnamurthy, Partha C; Penmatsa, Himabindu; Marrs, Kevin L; Wang, Xue Qing; Zaccolo, Manuela; Jalink, Kees; Li, Min; Nelson, Deborah J; Schuetz, John D; Naren, Anjaparavanda P


    Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated chloride channel localized at apical cell membranes and exists in macromolecular complexes with a variety of signaling and transporter molecules. Here, we report that the multidrug resistance protein 4 (MRP4), a cAMP transporter, functionally and physically associates with CFTR. Adenosine-stimulated CFTR-mediated chloride currents are potentiated by MRP4 inhibition, and this potentiation is directly coupled to attenuated cAMP efflux through the apical cAMP transporter. CFTR single-channel recordings and FRET-based intracellular cAMP dynamics suggest that a compartmentalized coupling of cAMP transporter and CFTR occurs via the PDZ scaffolding protein, PDZK1, forming a macromolecular complex at apical surfaces of gut epithelia. Disrupting this complex abrogates the functional coupling of cAMP transporter activity to CFTR function. Mrp4 knockout mice are more prone to CFTR-mediated secretory diarrhea. Our findings have important implications for disorders such as inflammatory bowel disease and secretory diarrhea.

  6. Cyclic AMP represents a crucial component of Treg cell-mediated immune regulation

    Directory of Open Access Journals (Sweden)

    Tobias Bopp


    Full Text Available T regulatory (Treg cells are one of the key players in the immune tolerance network (ITN and a plethora of manuscripts has described their development and function in the course of the last two decades. Nevertheless, it is still a matter of debate which mechanisms and agents are employed by Treg cells, providing the basis of their suppressive potency. One of the important candidates is cyclic AMP (cAMP which is long known as a potent suppressor at least of T cell activation and function. While this suppressive function by itself is widely accepted the source and the mechanism of action of cAMP are less clear and a multitude of seemingly contradictory data allow for in principle two different scenarios of cAMP-mediated suppression. In one scenario Treg cells contain high amounts of cAMP and convey this small molecule via gap junction intercellular communication (GJIC directly to the effector T cells (Teff leading to their suppression. Alternatively, it was shown that Treg cells represent the origin of considerable amounts of adenosine which trigger the adenylate cyclases (AC in Teff via A2A and A2B receptors thus strongly increasing intracellular cAMP. This review will present and discuss initial findings and recent developments concerning the function of cAMP for Treg cells and its impact on immune regulation.

  7. Looking downstream: the role of cyclic AMP-regulated genes in axonal regeneration

    Directory of Open Access Journals (Sweden)

    Mustafa M Siddiq


    Full Text Available Elevation of intracellular cyclic AMP (cAMP levels has proven to be one of the most effective means of overcoming inhibition of axonal regeneration by myelin-associated inhibitors such as myelin-associated glycoprotein, Nogo, and oligodendrocyte myelin glycoprotein. Pharmacological manipulation of cAMP through the administration of dibutyryl cAMP or rolipram leads to enhanced axonal growth both in vivo and in vitro, and importantly, upregulation of cAMP within dorsal root ganglion neurons is responsible for the conditioning lesion effect, which indicates that cAMP plays a significant role in the endogenous mechanisms that promote axonal regeneration. The effects of cAMP are transcription-dependent and are mediated through the activation of protein kinase A and the transcription factor CREB. This leads to the induction of a variety of genes, several of which have been shown to overcome myelin-mediated inhibition in their own right. In this review, we will highlight the pro-regenerative effects of arginase I, interleukin-6, secretory leukocyte protease inhibitor, and metallothionein-I/II, and discuss their potential for therapeutic use in spinal cord injury.

  8. cAMP Modulates Macrophage Development by Suppressing M-CSF-Induced MAPKs Activation

    Institute of Scientific and Technical Information of China (English)

    Ning Zhu; Jian Cui; Chunxia Qiao; Yan Li; Yuanfang Ma; Jiyan Zhang; Beifen Shen


    M-CSF is a key cytokine in macrophage development by inducing MAPKs activation, and cAMP can inhibit MAPKs activation induced by inflammatory stimuli. To explore the effects of cAMP on M-CSF-induced MAPKs activation and on macrophage development, the model of bone marrow-derived murine macrophages (BMMs) was used. The effects of cAMP on M-CSF-induced MAPKs activation were analyzed by Western blotting assay, and the effects of cAMP on CD14 and F4/80 expression during macrophage development were examined by FACS analysis.Macrophage morphology showed the successful establishment of the model of macrophage development. Western blotting assay revealed that M-CSF activated ERK, JNK and p38 in both mature and immature macrophages, and cAMP inhibited M-CSF-induced ERK, JNK and p38 activation in a time-dependent manner. FACS analysis revealed that macrophage development was impaired with cAMP pretreatment. In conclusion, cAMP modulates macrophage development by suppressing M-CSF-induced MAPKs activation.

  9. Cyclic-AMP regulation of calcium-dependent K channels in an insect central neurone. (United States)

    David, J A; Pitman, R M


    In the cockroach fast coxal depressor motoneurone, either the muscarinic agonist McN-A-343 or dibutyryl cAMP (Db-cAMP) induced a reduction in voltage-dependent outward current. The response to McN is due to suppression of a calcium-dependent potassium current (IK,Ca) produced secondarily to a reduction in voltage-dependent calcium current (ICa). The response to Db-cAMP was investigated in order to establish whether cAMP might mediate the response to McN. ICa was suppressed by 3-isobutyl-1-methylxanthine (IBMX) but not by Db-cAMP. The effects of IBMX were therefore unlikely to be the result of phosphodiesterase inhibition. Since caffeine also suppressed ICa, the observed effect of IBMX is probably due to release of Ca2+ from intracellular stores. IK,Ca, evoked by injection of Ca2+, was reduced by Db-cAMP or forskolin but not by McN. These results indicate that the electrical response to McN in this neurone is not mediated by changes in cAMP.

  10. Spatiotemporal Coupling of cAMP Transporter to CFTR Chloride Channel Function in the Gut Epithelia (United States)

    Li, Chunying; Krishnamurthy, Partha C.; Penmatsa, Himabindu; Marrs, Kevin L.; Wang, Xue Qing; Zaccolo, Manuela; Jalink, Kees; Li, Min; Nelson, Deborah J.; Schuetz, John D.; Naren, Anjaparavanda P.


    SUMMARY Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated chloride channel localized at apical cell membranes and exists in macromolecular complexes with a variety of signaling and transporter molecules. Here we report that the multidrug resistance protein 4 (MRP4), a cAMP transporter, is functionally and physically associates with CFTR. Adenosine-stimulated CFTR-mediated chloride currents are potentiated by MRP4 inhibition, and this potentiation is directly coupled to attenuated cAMP efflux through the apical cAMP transporter. CFTR single-channel recordings and FRET-based intracellular cAMP dynamics suggest that a compartmentalized coupling of cAMP transporter and CFTR occurs via the PDZ scaffolding protein, PDZK1, forming a macromolecular complex at apical surfaces of gut epithelia. Disrupting this complex abrogates the functional coupling of cAMP transporter activity to CFTR function. MRP4 knockout mice are more prone to CFTR-mediated secretory diarrhea. Our findings have important implications for disorders such as inflammatory bowel disease and secretory diarrhea. PMID:18045536

  11. New insight into the binding modes of TNP-AMP to human liver fructose-1,6-bisphosphatase (United States)

    Han, Xinya; Huang, Yunyuan; Zhang, Rui; Xiao, San; Zhu, Shuaihuan; Qin, Nian; Hong, Zongqin; Wei, Lin; Feng, Jiangtao; Ren, Yanliang; Feng, Lingling; Wan, Jian


    Human liver fructose-1,6-bisphosphatase (FBPase) contains two binding sites, a substrate fructose-1,6-bisphosphate (FBP) active site and an adenosine monophosphate (AMP) allosteric site. The FBP active site works by stabilizing the FBPase, and the allosteric site impairs the activity of FBPase through its binding of a nonsubstrate molecule. The fluorescent AMP analogue, 2‧,3‧-O-(2,4,6-trinitrophenyl)adenosine 5‧-monophosphate (TNP-AMP) has been used as a fluorescent probe as it is able to competitively inhibit AMP binding to the AMP allosteric site and, therefore, could be used for exploring the binding modes of inhibitors targeted on the allosteric site. In this study, we have re-examined the binding modes of TNP-AMP to FBPase. However, our present enzyme kinetic assays show that AMP and FBP both can reduce the fluorescence from the bound TNP-AMP through competition for FBPase, suggesting that TNP-AMP binds not only to the AMP allosteric site but also to the FBP active site. Mutagenesis assays of K274L (located in the FBP active site) show that the residue K274 is very important for TNP-AMP to bind to the active site of FBPase. The results further prove that TNP-AMP is able to bind individually to the both sites. Our present study provides a new insight into the binding mechanism of TNP-AMP to the FBPase. The TNP-AMP fluorescent probe can be used to exam the binding site of an inhibitor (the active site or the allosteric site) using FBPase saturated by AMP and FBP, respectively, or the K247L mutant FBPase.

  12. Detection of Amp C genes encoding for beta-lactamases in Escherichia coli and Klebsiella pneumoniae

    Directory of Open Access Journals (Sweden)

    M Shanthi


    Full Text Available Purpose : Amp C beta-lactamase are Ambler class C enzymes that confer resistance to extended spectrum cephalosporins and are not inhibited by beta-lactamase inhibitors. Their detection is crucial, since the phenotypic tests are not standardised leading to ambiguity in interpretation of results. This study was done to detect the types of Amp C prevalent in Escherichia coli and Klebsiella pneumoniae by multiplex polymerase chain reaction (PCR. Materials and Methods : Seventy-seven consecutive cefoxitin resistant clinical isolates of E. coli (n = 25 and K. pneumoniae (n = 52 were included in the study. Antibiotic susceptibility testing to various classes of antibiotics was performed by disc diffusion using Clinical Laboratory Standards Institute (CLSI guidelines. Minimum inhibitory concentration (MIC to cefoxitin, imipenem and meropenem were determined by broth microdilution method. Isolates were screened for production of Extended Spectrum Beta-Lactamase (ESBL. Multiplex PCR was performed for the detection of Amp C genes after phenotypic testing (Hodge test and inhibitor based test. Results : Cefoxitin Hodge test was positive in 40 isolates which included 20 E. coli and 20 K. pneumoniae. There was zone enhancement with boronic acid in 55 isolates, of which 36 were K. pneumoniae and 19 were E. coli. Multiplex PCR detected Amp C in 11/25 E. coli and 12/52 K. pneumoniae isolates. The Amp C genes detected were CIT (Amp C origin - Citrobacter freundii, DHA (Dhahran Hospital, Saudi Arabia, ACC (Ambler class C, EBC (Amp C origin - Enterobacter cloacae groups. ESBL was co-produced in 54 isolates. Conclusions : Amp C was detected in 29.87% of the study isolates. Majority of them co-produced ESBL. The most common Amp C was the CIT family. Screen tests for cefoxitin resistance may be falsely positive due to production of carbapenamases.

  13. The cyclic AMP cascade is altered in the fragile X nervous system.

    Directory of Open Access Journals (Sweden)

    Daniel J Kelley

    Full Text Available Fragile X syndrome (FX, the most common heritable cause of mental retardation and autism, is a developmental disorder characterized by physical, cognitive, and behavioral deficits. FX results from a trinucleotide expansion mutation in the fmr1 gene that reduces levels of fragile X mental retardation protein (FMRP. Although research efforts have focused on FMRP's impact on mGluR signaling, how the loss of FMRP leads to the individual symptoms of FX is not known. Previous studies on human FX blood cells revealed alterations in the cyclic adenosine 3', 5'-monophosphate (cAMP cascade. We tested the hypothesis that cAMP signaling is altered in the FX nervous system using three different model systems. Induced levels of cAMP in platelets and in brains of fmr1 knockout mice are substantially reduced. Cyclic AMP induction is also significantly reduced in human FX neural cells. Furthermore, cAMP production is decreased in the heads of FX Drosophila and this defect can be rescued by reintroduction of the dfmr gene. Our results indicate that a robust defect in cAMP production in FX is conserved across species and suggest that cAMP metabolism may serve as a useful biomarker in the human disease population. Reduced cAMP induction has implications for the underlying causes of FX and autism spectrum disorders. Pharmacological agents known to modulate the cAMP cascade may be therapeutic in FX patients and can be tested in these models, thus supplementing current efforts centered on mGluR signaling.

  14. Prolonged unassisted survival in an infant with anencephaly. (United States)

    Dickman, Holly; Fletke, Kyle; Redfern, Roberta E


    Anencephaly is one of the most lethal congenital defects. This case report is of an anencephalic infant who lived to 28 months of life and defies current literature. She is the longest surviving anencephalic infant who did not require life-sustaining interventions. This case presents the obstacles that arose from this infant's prolonged life and recommendations based on these findings.

  15. The Prolonged Neonatal Admission: Implications for our National Children's Hospital

    LENUS (Irish Health Repository)

    McGlacken-Byrne, SM


    A significant number of neonates are admitted to tertiary paediatric units for prolonged stays annually, despite limited availability of neonatal beds. As the three Dublin paediatric hospitals merge, this pressure will be transferred to our new National Children’s Hospital.\\r\

  16. Economic viability of beef cattle grazing systems under prolonged drought (United States)

    Prolonged drought in the Southern Great Plains of the USA in recent years has raised concerns about vulnerability of beef cattle grazing systems under adverse climate change. To help address the economic viability of beef grazing operations in the Southern Great Plains, this paper provides an econom...

  17. Prolonged idiopathic gastric dilatation following revascularization for chronic mesenteric ischemia. (United States)

    Gauci, Julia L; Stoven, Samantha; Szarka, Lawrence; Papadakis, Konstantinos A


    A 71-year-old female presented with nausea, emesis, early satiety, and abdominal distension following revascularization for chronic mesenteric ischemia. Computed tomography angiogram showed gastric dilatation. Esophagogastroduodenoscopy, small bowel follow through, and paraneoplastic panel were negative. Gastric emptying was delayed. Despite conservative management, she required a percutaneous endoscopic jejunostomy. The development of a prolonged gastroparetic state has not been previously described.

  18. Assessing QT interval prolongation and its associated risks with antipsychotics

    DEFF Research Database (Denmark)

    Nielsen, Jimmi; Graff, Claus; Kanters, Jørgen K.


    markers for TdP have been developed but none of them is clinically implemented yet and QT interval prolongation is still considered the most valid surrogate marker. Although automated QT interval determination may offer some assistance, QT interval determination is best performed by a cardiologist skilled...

  19. Brain activity and fatigue during prolonged exercise in the heat

    DEFF Research Database (Denmark)

    Hyldig, Tino Hoffmann


    We hypothesized that fatigue due to hyperthermia during prolonged exercise in the heat is in part related to alterations in frontal cortical brain activity. The electroencephalographic activity (EEG) of the frontal cortex of the brain was measured in seven cyclists [maximal O2 uptake (VO2max) 4...... min of exercise; P

  20. Effect of prolonged bed rest on the anterior hip muscles. (United States)

    Dilani Mendis, M; Hides, Julie A; Wilson, Stephen J; Grimaldi, Alison; Belavý, Daniel L; Stanton, Warren; Felsenberg, Dieter; Rittweger, Joern; Richardson, Carolyn


    Prolonged bed rest and inactivity is known to cause muscular atrophy with previous research indicating that muscles involved in joint stabilisation are more susceptible. The anterior hip muscles are important for hip joint function and stability but little is known about the effects of prolonged inactivity on their function. This study investigated the effect of prolonged bed rest on the size of the anterior hip muscles and their pattern of recovery. The effect of resistive vibration exercise (RVE) as a countermeasure to muscle atrophy was also investigated. 12 male participants, randomly assigned to either a control or an exercise group, underwent 8 weeks of bed rest with 6 months follow-up. Changes in muscle cross-sectional area (CSA) of the iliacus, psoas, iliopsoas, sartorius and rectus femoris muscles were measured by magnetic resonance imaging at regular intervals during bed rest and recovery phases. CSAs of iliopsoas and sartorius decreased at the hip joint (piliacus, psoas, and rectus femoris CSAs were unchanged (p>0.05). No significant difference was found between the two groups for all muscles (all p>0.1), suggesting inefficacy of the countermeasure in this sample. These findings suggest that prolonged bed rest can result in the atrophy of specific muscles across the hip joint which may affect its stability and function.

  1. Cerebral ammonia uptake and accumulation during prolonged exercise in humans

    DEFF Research Database (Denmark)

    Nybo, Lars; Dalsgaard, Mads K.; Steensberg, Adam


    We evaluated whether peripheral ammonia production during prolonged exercise enhances the uptake and subsequent accumulation of ammonia within the brain. Two studies determined the cerebral uptake of ammonia (arterial and jugular venous blood sampling combined with Kety-Schmidt-determined cerebra...

  2. Prolonged drought results in starvation of African elephant (Loxodonta africana)

    NARCIS (Netherlands)

    Wato, Yussuf A.; Heitkonig, Ignas; Wieren, van Sipke E.; Wahungu, Geoffrey; Prins, Herbert H.T.; Langevelde, van Frank


    Elephant inhabiting arid and semi-arid savannas often experience periods of drought, which, if prolonged, may cause mortality. During dry periods, elephant aggregate around water sources and deplete local forage availability. However, the relationships between adult elephant mortality and both hi

  3. Intrinsic motivation and amotivation in first episode and prolonged psychosis. (United States)

    Luther, Lauren; Lysaker, Paul H; Firmin, Ruth L; Breier, Alan; Vohs, Jenifer L


    The deleterious functional implications of motivation deficits in psychosis have generated interest in examining dimensions of the construct. However, there remains a paucity of data regarding whether dimensions of motivation differ over the course of psychosis. Therefore, this study examined two motivation dimensions, trait-like intrinsic motivation, and the negative symptom of amotivation, and tested the impact of illness phase on the 1) levels of these dimensions and 2) relationship between these dimensions. Participants with first episode psychosis (FEP; n=40) and prolonged psychosis (n=66) completed clinician-rated measures of intrinsic motivation and amotivation. Analyses revealed that when controlling for group differences in gender and education, the FEP group had significantly more intrinsic motivation and lower amotivation than the prolonged psychosis group. Moreover, intrinsic motivation was negatively correlated with amotivation in both FEP and prolonged psychosis, but the magnitude of the relationship did not statistically differ between groups. These findings suggest that motivation deficits are more severe later in the course of psychosis and that low intrinsic motivation may be partially independent of amotivation in both first episode and prolonged psychosis. Clinically, these results highlight the importance of targeting motivation in early intervention services.

  4. Single Prolonged Stress Disrupts Retention of Extinguished Fear in Rats (United States)

    Knox, Dayan; George, Sophie A.; Fitzpatrick, Christopher J.; Rabinak, Christine A.; Maren, Stephen; Liberzon, Israel


    Clinical research has linked post-traumatic stress disorder (PTSD) with deficits in fear extinction. However, it is not clear whether these deficits result from stress-related changes in the acquisition or retention of extinction or in the regulation of extinction memories by context, for example. In this study, we used the single prolonged stress…

  5. Prolongation Structure of Semi-discrete Nonlinear Evolution Equations

    Institute of Scientific and Technical Information of China (English)


    Based on noncommutative differential calculus, we present a theory of prolongation structure for semi-discrete nonlinear evolution equations. As an illustrative example, a semi-discrete model of the nonlinear Schr(o)dinger equation is discussed in terms of this theory and the corresponding Lax pairs are also given.

  6. Examining potential contraindications for prolonged exposure therapy for PTSD

    NARCIS (Netherlands)

    Minnen, A. van; Harned, M.S.; Zöllner, L.; Mills, K.


    Although prolonged exposure (PE) has received the most empirical support of any treatment for posttraumatic stress disorder (PTSD), clinicians are often hesitant to use PE due to beliefs that it is contraindicated for many patients with PTSD. This is especially true for PTSD patients with comorbid p

  7. Delirium in Prolonged Hospitalized Patients in the Intensive Care Unit

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    Vahedian Azimi


    Full Text Available Background Prolonged hospitalization in the intensive care unit (ICU can impose long-term psychological effects on patients. One of the most significant psychological effects from prolonged hospitalization is delirium. Objectives The aim of this study was to assess the effect of prolonged hospitalization of patients and subsequent delirium in the intensive care unit. Patients and Methods This conventional content analysis study was conducted in the General Intensive Care Unit of the Shariati Hospital of Tehran University of Medical Sciences, from the beginning of 2013 to 2014. All prolonged hospitalized patients and their families were eligible participants. From the 34 eligible patients and 63 family members, the final numbers of actual patients and family members were 9 and 16, respectively. Several semi-structured interviews were conducted face-to-face with patients and their families in a private room and data were gathered. Results Two main themes from two different perspectives emerged, 'patients' perspectives' (experiences during ICU hospitalization and 'family members' perspectives' (supportive-communicational experiences. The main results of this study focused on delirium, Patients' findings were described as pleasant and unpleasant, factual and delusional experiences. Conclusions Family members are valuable components in the therapeutic process of delirium. Effective use of family members in the delirium caring process can be considered to be one of the key non-medical nursing components in the therapeutic process.

  8. Morphological and mechanical characterization of chitosan-calcium phosphate composites for potential application as bone-graft substitutes

    Directory of Open Access Journals (Sweden)

    Guilherme Maia Mulder van de Graaf

    Full Text Available Introduction: Bone diseases, aging and traumas can cause bone loss and lead to bone defects. Treatment of bone defects is challenging, requiring chirurgical procedures. Bone grafts are widely used for bone replacement, but they are limited and expensive. Due to bone graft limitations, natural, semi-synthetic, synthetic and composite materials have been studied as potential bone-graft substitutes. Desirable characteristics of bone-graft substitutes are high osteoinductive and angiogenic potentials, biological safety, biodegradability, bone-like mechanical properties, and reasonable cost. Herein, we prepared and characterized potential bone-graft substitutes composed of calcium phosphate (CP - a component of natural bone, and chitosan (CS - a biocompatible biopolymer. Methods CP-CS composites were synthetized, molded, dried and characterized. The effect of drying temperatures (38 and 60 °C on the morphology, porosity and chemical composition of the composites was evaluated. As well, the effects of drying temperature and period of drying (3, 24, 48 and 72 hours on the mechanical properties - compressive strength, modulus of elasticity and relative deformation-of the demolded samples were investigated. Results Scanning electron microscopy and gas adsorption-desorption analyses of the CS-CP composites showed interconnected pores, indicating that the drying temperature played an important role on pores size and distribution. In addition, drying temperature have altered the color (brownish at 60 °C due to Maillard reaction and the chemical composition of the samples, confirmed by FTIR. Conclusion Particularly, prolonged period of drying have improved mechanical properties of the CS-CP composites dried at 38 °C, which can be designed according to the mechanical needs of the replaceable bone.

  9. ESR spectroscopic investigations of the radiation-grafting of fluoropolymers

    Energy Technology Data Exchange (ETDEWEB)

    Huebner, G.; Roduner, E. [University of Stuttgart (Germany); Brack, H.P.; Scherer, G.G. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)


    ESR spectroscopic investigations have clarified the influence of several preparative parameters on the reaction rates and yields obtained in the radiation-grafting method used at PSI to prepare proton-conducting polymer membranes. At a given irradiation dose, a higher concentration of reactive radical sites was detected in ETFE films than in FEP films. This higher concentration explains the higher grafting levels and rates of the ETFE films found in our previous grafting experiments. Taken together, the in-situ ESR experiments and grafting experiments show that the rates of disappearance of radical species and grafting rates and final grafting levels depend strongly on the reaction temperature and the oxygen content of the system. Average grafted chain lengths were calculated to contain about 1,000 monomer units. (author) 2 figs., 4 refs.

  10. Cyclic AMP-dependent protein kinase I: Cyclic nucleotide binding, structural changes, and release of the catalytic subunits


    Smith, Stephen B.; White, Hillary D.; Siegel, Jeffrey B.; Krebs, Edwin G.


    Type I cyclic AMP (cAMP)-dependent protein kinase is composed of a dimeric regulatory subunit (R2) and two catalytic subunits (C subunits). The R2 dimer binds four cAMP molecules to release the two C subunits. To characterize the cAMP binding sites and elucidate their role in the release of the C subunits, the R2 dimer has been studied by equilibrium methods. The cAMP titration of R2 was monitored by endogenous tryptophan fluorescence, and the results suggest one class of binding sites. The t...

  11. Reflection principle for classical solutions of the homogeneous real Monge–Ampère equation

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    Mika Koskenoja


    Full Text Available We consider reflection principle for classical solutions of the homogeneous real Monge–Ampère equation. We show that both the odd and the even reflected functions satisfy the Monge–Ampère equation if the second-order partial derivatives have continuous limits on the reflection boundary. In addition to sufficient conditions, we give some necessary conditions. Before stating the main results, we present elementary formulas for the reflected functions and study their differentiability properties across the reflection boundary. As an important special case, we finally consider extension of polynomials satisfying the homogeneous Monge–Ampère equation.

  12. Effect of cAMP on short-circuit current in isolated human ciliary body

    Institute of Scientific and Technical Information of China (English)

    WU Ren-yi; MA Ning; HU Qian-qian


    Background Cyclic adenosine monophosphate (cAMP) could activate chloride channels in bovine ciliary body and trigger an increase in the ionic current (short-circuit current,Isc) across the ciliary processes in pigs.The purpose of this study was to investigate how cAMP modulates Isc in isolated human ciliary processes and the possible involvement of chloride transport across the tissue in cAMP-induced Isc change.Methods In an Ussing-type chamber system,the Isc changes induced by the cAMP analogue 8-bromo-cAMP and an adenylyl cyclase activator forskolin in isolated human ciliary processes were assessed.The involvement of Cl-component in the bath solution was investigated.The effect of Cl-channel (10 μmol/L niflumic acid and 1 mmol/L 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS)),K+ channel (10 mmol/L tetraethylammonium chloride (TEA)),or Na+ channel blockers (1 mmol/L amiloride) on 8-bromo-cAMP-induced Isc change was also studied.Results Dose-dependently,8-bromo-cAMP (10 nmol/L-30 μmol/L) or forskolin (10 nmol/L-3 μmol/L) increased Isc across the ciliary processes with an increase in negative potential difference on the non-pigmented epithelium (NPE) side of the tissue.Isc increase induced by 8-bromo-cAMP was more pronounced when the drug was applied on the NPE side than on the pigmented epithelium side.When the tissue was bathed in low Cl-solutions,the Isc increase was significantly inhibited.Finally,niflumic acid and DIDS,but not TEA or amiloride,significantly prevented the Isc increase induced by 8-bromo-cAMP.Conclusions cAMP stimulates stroma-to-aqueous anionic transport in isolated human ciliary processes.Chloride is likely to be among the ions,the transportation of which across the tissue is triggered by cAMP,suggesting the potential role of cAMP in the process of aqueous humor formation in human eyes.

  13. Comparison of cAMP with other radioprotectors against chronic damage to the rat parotid gland

    Energy Technology Data Exchange (ETDEWEB)

    Conger, A.D.; Sodicoff, M.; Samel, A.


    Radiation damage to the parotid gland is protectable by cAMP during the first week after irradiation (acute phase), though appreciable recovery occurred later with or without such protection. Further damage developed later (chronic phase, 60-90 days), and cAMP was still protective against this damage with a dose modification factor of 1.86 for gland weight. A summary of the protective factors, acute and chronic, for WR-2721, isoproterenol, and cAMP is included. Chronic damage is about 1.5 times as great as acute, and protection against acute and chronic damage is about equal for all three compounds.

  14. A high-speed CMOS current op amp for very low supply voltage operation

    DEFF Research Database (Denmark)

    Bruun, Erik


    A CMOS implementation of a high-gain current mode operational amplifier (op amp) with a single-ended input and a differential output is described. This configuration is the current mode counterpart of the traditional voltage mode op amp. In order to exploit the inherent potential for high speed......, low voltage operation normally associated with current mode analog signal processing, the op amp has been designed to operate off a supply voltage of 1.5 V, and the signal path has been confined to N-channel transistors. With this design, a gain of 94 dB and a gain-bandwidth product of 65 MHz has been...

  15. Analysis of Advanced Modular Power Systems (AMPS) for Deep Space Exploration (United States)

    Oeftering, Richard; Soeder, James F.; Beach, Ray


    The Advanced Modular Power Systems (AMPS) project is developing a modular approach to spacecraft power systems for exploration beyond Earth orbit. AMPS is intended to meet the need of reducing the cost of design development, test and integration and also reducing the operational logistics cost of supporting exploration missions. AMPS seeks to establish modular power building blocks with standardized electrical, mechanical, thermal and data interfaces that can be applied across multiple exploration vehicles. The presentation discusses the results of a cost analysis that compares the cost of the modular approach against a traditional non-modular approach.

  16. Characterization of cyclic AMP accumulation in cultured human corpus cavernosum smooth muscle cells. (United States)

    Palmer, L S; Valcic, M; Melman, A; Giraldi, A; Wagner, G; Christ, G J


    Intracavernous pharmacotherapy relies heavily on the use of vasoactive agents which act by increasing intracellular cAMP levels in human corpus cavernosum smooth muscle. Yet little is known about the cAMP generating system in this tissue, and how it may affect observed patient variability. Thus, the goal of these studies was to better characterize the biochemistry of cAMP formation in human corpus cavernosum smooth muscle, and thus provide more insight into the mechanisms of corporal smooth muscle relaxation in vivo. We studied both receptor and nonreceptor mediated increases in cAMP formation in short-term cultures of human corpus cavernosum smooth muscle cells. Both isoproterenol (ISO) and prostaglandin E1 (PGE1) produced concentration-dependent increases in cAMP, but histamine, serotonin and vasoactive intestinal polypeptide did not. Forskolin, a relatively specific activator of adenylate cyclase, was also a potent stimulant of cAMP formation in these cells. Moreover, there was a direct correlation between the degree of forskolin-induced cAMP accumulation in cultured corporal smooth muscle cells and the magnitude of the forskolin-induced relaxation response of precontracted isolated corporal smooth muscle strips. Prostaglandin E1 and ISO concentration response curves (CRCs) were then assayed in the absence and presence of subthreshold forskolin (0.1 microM.). In the presence of forskolin, the calculated maximal PGE1-induced cAMP accumulation (Emax) was significantly greater than that elicited by PGE1 alone, ISO alone, or ISO + forskolin (p protocol was used to demonstrate that both 80:20 and 70:30 FMRs (but not 95:5 or 90:10), were associated with significantly greater cAMP Emax values than that observed for PGE1 alone (p < or = 0.01). These data provide direct evidence that the degree of cAMP formation in cultured corporal smooth muscle cells is strongly correlated with the magnitude of relaxation of isolated corporal smooth muscle strips. In addition, since

  17. Detection of ESBLs,AmpC β-Lactamase and AmpC genotype in Enterobacter cloacae and analysis of their drug resistance%阴沟肠杆菌ESBLs、AmpC酶和AmpC酶基因型的检测及耐药性分析

    Institute of Scientific and Technical Information of China (English)

    林平; 陈佳玉


    目的 探讨阴沟肠杆菌ESBLs和AmpC酶的产生情况、AmpC酶的耐药基因型及对常用抗菌药物的耐药特征,为临床治疗提供选药参考.方法 采用VITEK-60型全自动细菌鉴定仪鉴定细菌,按美国临床实验室标准化委员会(CLSI)推荐的确证试验检测超广谱β-内酰胺酶(ESBLs)和K-B纸片法测定药敏结果;采用头孢西丁纸片扩散法筛选疑产AmpC酶阳性菌株,并通过酶粗提物头孢西丁三维试验、接合试验、PCR测序等实验分析该菌株的基因型.结果 157株阴沟肠杆菌ESBLs和AmpC酶总检出率分别为31.21%和32.48%,其中,单产AmpC酶、同产AmpC酶+ESBLs、单产ESBLs检出率分别为17.20%、7.64%和23.57%;AmpC酶阳性菌株的耐药基因型:30株为DHA型,9株为CIT型.产酶株的耐药性明显高于非产酶株,耐药现象在同产AmpC酶和ESBLs菌株中更为严重,产与非产AmpC酶(和)ESBLs菌株对哑胺培南的敏感率几乎达100%.结论 台州地区阴沟肠杆菌产ESBLs和AmpC酶菌株检出率较高,AmpC酶以DHA-1基因型为主.产AmpC酶和ESBLs的菌株呈高度耐药,限制β-内酰胺类抗菌药物的应用是减少产酶株流行的重要措施.

  18. AmpC酶阴沟肠杆菌的检测

    Institute of Scientific and Technical Information of China (English)




  19. Cyclic 3', 5'-AMP relay in Dictyostelium discoideum: adaptation is independent of activation of adenylate cyclase



    In Dictyostelium discoideum, binding of cAMP to high affinity surface receptors leads to a rapid activation of adenylate cyclase followed by subsequent adaptation within several minutes. The rate of secretion of [ 3H ]cAMP, which reflects the state of activation of the enzyme, was measured. Caffeine noncompetitively inhibited the response to cAMP. Inhibition was rapidly reversible and pretreatment of cells with caffeine for up to 22 min had little effect on the subsequent responsiveness to cA...

  20. Gene Expression Patterns Define Key Transcriptional Events InCell-Cycle Regulation By cAMP And Protein Kinase A

    Energy Technology Data Exchange (ETDEWEB)

    Zambon, Alexander C.; Zhang, Lingzhi; Minovitsky, Simon; Kanter, Joan R.; Prabhakar, Shyam; Salomonis, Nathan; Vranizan, Karen; Dubchak Inna,; Conklin, Bruce R.; Insel, Paul A.


    Although a substantial number of hormones and drugs increase cellular cAMP levels, the global impact of cAMP and its major effector mechanism, protein kinase A (PKA), on gene expression is not known. Here we show that treatment of murine wild-type S49 lymphoma cells for 24 h with 8-(4-chlorophenylthio)-cAMP (8-CPTcAMP), a PKA-selective cAMP analog, alters the expression of approx equal to 4,500 of approx. equal to 13,600 unique genes. By contrast, gene expression was unaltered in Kin- S49 cells (that lack PKA) incubated with 8-CPTcAMP. Changes in mRNA and protein expression of several cell cycle regulators accompanied cAMP-induced G1-phase cell-cycle arrest of wild-type S49 cells. Within 2h, 8-CPT-cAMP altered expression of 152 genes that contain evolutionarily conserved cAMP-response elements within 5 kb of transcriptional start sites, including the circadian clock gene Per1. Thus, cAMP through its activation of PKA produces extensive transcriptional regulation in eukaryotic cells. These transcriptional networks include a primary group of cAMP-response element-containing genes and secondary networks that include the circadian clock.

  1. HeLa human cervical cancer cell migration is inhibited by treatment with dibutyryl-cAMP. (United States)

    Lee, Jae-Wook; Lee, Jiyoung; Moon, Eun-Yi


    Cyclic AMP (cAMP) activates both protein kinase A (PKA) and guanine-nucleotide exchange factor exchange protein directly activated by CAMP (EPAC)-mediated Ras-related Protein1 (RAP1) GTPase that regulates various cellular functions including cell migration. Herein, we investigated whether cAMP-mediated PKA and EPAC1/RAP1 pathways differentially control HeLa cervical cancer cell migration. Although HeLa cell migration was reduced by dibutyryl-cAMP, we observed an increase in cAMP/PKA, cAMP/EPAC1/RAP1-GTPase, and RAC1-GTPase. HeLa cell migration and RAC1-GTPase were increased by treatment with 8-(4-chloro-phenylthio)-2'-O-methyladenosine-3',5'-cAMP analogue to activate EPAC-specific signaling pathways. When HeLa cells were treated with H-89, a PKA inhibitor, cell migration was enhanced but RAC1-GTPase was inhibited. In addition, cell migration induced by dibutyryl-cAMP was reversed but the activity of Rac1-GTPase was inhibited by H-89 treatment. Taken together, these data demonstrate that cAMP/PKA and cAMP/EPAC1/RAP1-GTPase might inversely control cervical cancer cell migration, although both signaling pathways may up-regulate RAC1-GTPase. It also suggests that cAMP-mediated cancer cell migration was independent of RAC1-GTPase activation.

  2. Removal characteristics of CO2 using aqueous MEA/AMP solutions in the absorption and regeneration process

    Institute of Scientific and Technical Information of China (English)

    Won-Joon Choi; Jong-Beom Seo; Sang-Yong Jang; Jong-Hyeon Jung; Kwang-Joong Oh


    The carbon dioxide (CO2) removal efficiency, reaction rate, and CO2 loading into aqueous blended monoethanolamine (MEA) + 2-amino-2-methyl-1-propanol (AMP) solutions to enhance absorption characteristics of MEA and AMP were carried out by the absorption/regeneration process. As a result, compared to aqueous MEA and AMP solutions, aqueous blended MEA+AMP solutions have a higher CO2 loading than MEA and a higher reaction rate than AMP. The CO2 loading of rich amine of aqueous 18 wt.% MEA+12 wt.% AMP solution was 0.62 mol CO2/mol amine, which is 51.2% more than 30 wt.% MEA (0.41 mol CO2/mol amine). Consequently, blending MEA and AMP could be an effective way to design cousidering economical efficiency and used to operate absorber for a long time.

  3. Mesenchymal stem cells increase skin graft survival time and up-regulate PD-L1 expression in splenocytes of mice. (United States)

    Moravej, Ali; Geramizadeh, Bita; Azarpira, Negar; Zarnani, Amir-Hassan; Yaghobi, Ramin; Kalani, Mehdi; Khosravi, Maryam; Kouhpayeh, Amin; Karimi, Mohammad-Hossein


    Recently, mesenchymal stem cells (MSCs) have gained considerable interests as hopeful therapeutic cells in transplantation due to their immunoregulatory functions. But exact mechanisms underlying MSCs immunoregulatory function is not fully understood. Herein, in addition to investigate the ability of MSCs to prolong graft survival time, the effects of them on the expression of PD-L1 and IDO immunomodulatory molecules in splenocytes of skin graft recipient mice was clarified. To achieve this goal, full-thickness skins were transplanted from C57BL/6 to BALB/c mice. MSCs were isolated from bone marrow of BALB/c mice and injected to the recipient mice. Skin graft survival was monitored daily to determine graft rejection time. On days 2, 5 and 10 post skin transplantation, serum cytokine levels and expression of PD-L1 and IDO mRNA and protein in the splenocytes of recipient mice were evaluated. The results showed that administration of MSCs prolonged skin graft survival time from 11 to 14 days. On days 2 and 5 post transplantation, splenocytes PD-L1 expression and IL-10 serum level in MSCs treated mice were higher than those in the controls, while IL-2 and IFN-γ levels were lower. Rejection in MSCs treated mice was accompanied by an increase in IL-2 and IFN-γ, and decrease in PD-L1 expression and IL-10 level. No difference in the expression of IDO between MSCs treated mice and controls was observed. In conclusion, we found that one of the mechanisms underlying MSCs immunomodulatory function could be up-regulating PD-L1 expression.

  4. The cAMP analogs have potent anti-proliferative effects on medullary thyroid cancer cell lines. (United States)

    Dicitore, Alessandra; Grassi, Elisa Stellaria; Caraglia, Michele; Borghi, Maria Orietta; Gaudenzi, Germano; Hofland, Leo J; Persani, Luca; Vitale, Giovanni


    The oncogenic activation of the rearranged during transfection (RET) proto-oncogene has a main role in the pathogenesis of medullary thyroid cancer (MTC). Several lines of evidence suggest that RET function could be influenced by cyclic AMP (cAMP)-dependent protein kinase A (PKA) activity. We evaluated the in vitro anti-tumor activity of 8-chloroadenosine-3',5'-cyclic monophosphate (8-Cl-cAMP) and PKA type I-selective cAMP analogs [equimolar combination of the 8-piperidinoadenosine-3',5'-cyclic monophosphate (8-PIP-cAMP) and 8-hexylaminoadenosine-3',5'-cyclic monophosphate (8-HA-cAMP) in MTC cell lines (TT and MZ-CRC-1)]. 8-Cl-cAMP and the PKA I-selective cAMP analogs showed a potent anti-proliferative effect in both cell lines. In detail, 8-Cl-cAMP blocked significantly the transition of TT cell population from G2/M to G0/G1 phase and from G0/G1 to S phase and of MZ-CRC-1 cells from G0/G1 to S phase. Moreover, 8-Cl-cAMP induced apoptosis in both cell lines, as demonstrated by FACS analysis for annexin V-FITC/propidium iodide, the activation of caspase-3 and PARP cleavage. On the other hand, the only effect induced by PKA I-selective cAMP analogs was a delay in G0/G1-S and S-G2/M progression in TT and MZ-CRC-1 cells, respectively. In conclusion, these data demonstrate that cAMP analogs, particularly 8-Cl-cAMP, significantly suppress in vitro MTC proliferation and provide rationale for a potential clinical use of cAMP analogs in the treatment of advanced MTC.

  5. Activating AMP-activated protein kinase (AMPK) slows renal cystogenesis. (United States)

    Takiar, Vinita; Nishio, Saori; Seo-Mayer, Patricia; King, J Darwin; Li, Hui; Zhang, Li; Karihaloo, Anil; Hallows, Kenneth R; Somlo, Stefan; Caplan, Michael J


    Renal cyst development and expansion in autosomal dominant polycystic kidney disease (ADPKD) involves both fluid secretion and abnormal proliferation of cyst-lining epithelial cells. The chloride channel of the cystic fibrosis transmembrane conductance regulator (CFTR) participates in secretion of cyst fluid, and the mammalian target of rapamycin (mTOR) pathway may drive proliferation of cyst epithelial cells. CFTR and mTOR are both negatively regulated by AMP-activated protein kinase (AMPK). Metformin, a drug in wide clinical use, is a pharmacological activator of AMPK. We find that metformin stimulates AMPK, resulting in inhibition of both CFTR and the mTOR pathways. Metformin induces significant arrest of cystic growth in both in vitro and ex vivo models of renal cystogenesis. In addition, metformin administration produces a significant decrease in the cystic index in two mouse models of ADPKD. Our results suggest a possible role for AMPK activation in slowing renal cystogenesis as well as the potential for therapeutic application of metformin in the context of ADPKD.

  6. Hypoxia inhibits colonic ion transport via activation of AMP kinase.

    LENUS (Irish Health Repository)

    Collins, Danielle


    BACKGROUND AND AIMS: Mucosal hypoxia is a common endpoint for many pathological processes including ischemic colitis, colonic obstruction and anastomotic failure. Previous studies suggest that hypoxia modulates colonic mucosal function through inhibition of chloride secretion. However, the molecular mechanisms underlying this observation are poorly understood. AMP-activated protein kinase (AMPK) is a metabolic energy regulator found in a wide variety of cells and has been linked to cystic fibrosis transmembrane conductance regulator (CFTR) mediated chloride secretion in several different tissues. We hypothesized that AMPK mediates many of the acute effects of hypoxia on human and rat colonic electrolyte transport. METHODS: The fluorescent chloride indicator dye N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide was used to measure changes in intracellular chloride concentrations in isolated single rat colonic crypts. Ussing chamber experiments in human colonic mucosa were conducted to evaluate net epithelial ion transport. RESULTS: This study demonstrates that acute hypoxia inhibits electrogenic chloride secretion via AMPK mediated inhibition of CFTR. Pre-treatment of tissues with the AMPK inhibitor 6-[4-(2-piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo [1,5-a] pyrimidine (compound C) in part reversed the effects of acute hypoxia on chloride secretion. CONCLUSION: We therefore suggest that AMPK is a key component of the adaptive cellular response to mucosal hypoxia in the colon. Furthermore, AMPK may represent a potential therapeutic target in diseased states or in prevention of ischemic intestinal injury.

  7. Novel anterior cruciate ligament graft fixation device reduces slippage

    Directory of Open Access Journals (Sweden)

    Lopez MJ


    Full Text Available Mandi J Lopez,1 Allen Borne,2 W Todd Monroe,3 Prakash Bommala,1 Laura Kelly,1 Nan Zhang11Laboratory for Equine and Comparative Orthopedic Research, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, 2Louisiana State University, New Orleans Health Sciences Center, School of Medicine, New Orleans, 3Department of Biological and Agricultural Engineering, Agricultural Center, Louisiana State University, Baton Rouge, LA, USAAbstract: Clinically significant laxity occurs in 10%–30% of knees after anterior cruciate ligament reconstruction. Graft slippage and tension loss at the hamstring graft tibial fixation site during and after reconstruction surgery contribute to postoperative joint laxity and are detrimental to long-term knee stability and graft properties. Limiting graft slippage will reduce associated complications. We sought to compare the in vitro mechanical properties and in vivo joint stabilization, postoperative limb use, and graft incorporation of the novel GraftGrab™ (GG device designed to reduce hamstring graft tibial fixation slippage with the commercially available bioabsorbable Bio-Post™ and spiked washer (BP. Mechanical testing was performed on canine tibia-hamstring graft constructs to quantify initial fixation properties. In vivo joint stabilization, postoperative limb use and graft incorporation of hamstring graft reconstructions were determined in a canine model. Outcomes included tibial translation and ground reaction forces preoperatively and 4 and 8 weeks postoperatively, three-dimensional graft and bone tunnel dimensions at the latter two time points, and graft-bone microstructure, as well as mechanical properties 8 weeks after implantation. Immediately after fixation, all grafts slipped from the BP constructs versus about 30% of GG constructs. In vivo limb use remained low, and tibial translation increased with time in the BP cohort. These results together

  8. [Bovine heterologous bone graft in orbital surgery]. (United States)

    Morax, S; Hurbli, T; Smida, R


    Lubboc (T650) is a bovine heterologous bone implant obtained by specific preparation of trabecular of bone. In vitro and in vivo biocompatibility studies have revealed the absence of any cytotoxicity or systemic toxicity. Lubboc has many fields of application, including all bone graft surgical indications. We report our first results concerning the use of this product in orbital surgery either as a filling or contention material or as an apposition material. On all 20 operated patients we did not encounter any intolerance, inflammation or infection. The follow-up is still too short to appreciate the long term integration of this material which has the advantage of being a substitute for autologous bone, avoiding bone graft harvesting.

  9. Primary Graft Failure after Heart Transplantation

    Directory of Open Access Journals (Sweden)

    Arjun Iyer


    Full Text Available Primary graft failure (PGF is a devastating complication that occurs in the immediate postoperative period following heart transplantation. It manifests as severe ventricular dysfunction of the donor graft and carries significant mortality and morbidity. In the last decade, advances in pharmacological treatment and mechanical circulatory support have improved the outlook for heart transplant recipients who develop this complication. Despite these advances in treatment, PGF is still the leading cause of death in the first 30 days after transplantation. In today's climate of significant organ shortages and growing waiting lists, transplant units worldwide have increasingly utilised “marginal donors” to try and bridge the gap between “supply and demand.” One of the costs of this strategy has been an increased incidence of PGF. As the threat of PGF increases, the challenges of predicting and preventing its occurrence, as well as the identification of more effective treatment modalities, are vital areas of active research and development.

  10. A QM/MM study of the 5‧-AMP DNA hydrolysis of aprataxin (United States)

    Hanaoka, Kyohei; Tanaka, Wataru; Kayanuma, Megumi; Shoji, Mitsuo


    Aprataxin is a DNA repair enzyme that hydrolyzes the abnormal 5‧-AMP termini of broken DNAs. Based on quantum mechanical/molecular mechanical (QM/MM) calculations, we found that the catalytic reaction proceeds in three steps; substrate protonation, DNA deadenylation and histidine-AMP intermediate hydrolysis. The calculated activation energies for the second and third reactions are 19.0 and 10.5 kcal mol-1, which can be attributed to a penta-coordinated AMP-phosphoryl formation and closing of a water molecule, respectively. We also found that a histidine-AMP intermediate is hydrolyzed easily in the third step when a water molecule closes within 3 Å to the phosphorus nucleus.

  11. Use of phenylthiocarbamide for assessing cAMP-dependent resistance to anoxia in animals. (United States)

    Bolekhan, E A; Semenov, D G; Gerasimova, I A; Samoilov, M O


    The responses of cats with different levels of taste sensitivity to phenylthiocarbamide (PTC) bitters to five-minute hypoxia were studied; PTC sensitivity is a genetic marker of the activity of the cAMP system. Animals able to perceive PTC showed a number of functional differences, with higher levels of resistance to anoxia, than those which could not perceive PTC. The groups showed significant differences in the basal cAMP content in the cerebral cortex, and in the time course of changes in the cAMP level during anoxia and subsequent reoxygenation. It is suggested that these differences result from genetically determined features of the cAMP system, which is involved in forming adaptive responses.

  12. Selective Phosphonylation of 5'-Adenosine Monophosphate (5'-AMP) via Pyrophosphite [PPi(III) (United States)

    Kaye, Karl; Bryant, David E.; Marriott, Katie E. R.; Ohara, Shohei; Fishwick, Colin W. G.; Kee, Terence P.


    We describe here experiments which demonstrate the selective phospho-transfer from a plausibly prebiotic condensed phosphorus (P) salt, pyrophosphite [H2P2O5 2-; PPi(III)], to the phosphate group of 5'-adenosine mono phosphate (5'-AMP). We show further that this P-transfer process is accelerated both by divalent metal ions (M2+) and by organic co-factors such as acetate (AcO-). In this specific case of P-transfer from PPi(III) to 5'-AMP, we show a synergistic enhancement of transfer in the combined presence of M2+ & AcO-. Isotopic labelling studies demonstrate that hydrolysis of the phosphonylated 5'-AMP, [P(III)P(V)-5'-AMP], proceeds via nuceophilic attack of water at the Pi(III) terminus.

  13. N-Acetyl-D- and L-esters of 5'-AMP hydrolyze at different rates (United States)

    Wickramasinghe, N. S.; Lacey, J. C. Jr; Lacey JC, J. r. (Principal Investigator)


    Studies of the properties of aminoacyl derivatives of 5'-AMP are aimed at understanding the origin of the process of protein synthesis. Aminoacyl (2',3') esters of 5'-AMP can serve as models of the 3'-terminus of aminoacyl tRNA. We report here on the relative rates of hydrolysis of Ac-D- and L-Phe AMP esters as a function of pH. At all pHs above 3, the rate constant of hydrolysis of the Ac-L-Phe ester is 1.7 to 2.1 times that of Ac-D-Phe ester. The D-isomer seems partially protected from hydrolysis by a stronger association with the adenine ring of the 5'-AMP.

  14. Progression from stenosis to occlusion in the proximal native coronary artery after coronary artery bypass grafting. (United States)

    Tanaka, Akihito; Ishii, Hideki; Oshima, Hideki; Shibata, Yohei; Tatami, Yosuke; Osugi, Naohiro; Ota, Tomoyuki; Kawamura, Yoshihiro; Suzuki, Susumu; Usui, Akihiko; Murohara, Toyoaki


    Coronary artery bypass grafting (CABG) is an established treatment for multivessel coronary artery disease. However, problematic situations are occasionally encountered after CABG, such as disease progression in the native coronary artery with graft occlusion, which causes difficulty in revascularization. The purpose of this study was to evaluate changes in the native coronary artery after CABG. Between 2009 and 2012 in our institution, 351 patients underwent CABG, and 768 bypass grafts were anastomosed to non-occluded coronary arteries. Of these, 489 bypass grafts had available early postoperative angiographic results (≤6 months) suitable for assessment in this study. We defined malignant graft failure after CABG to be bypass graft occlusion and de novo complete occlusion of the target native coronary artery proximal to the graft anastomosis site. In the early angiographic results, 17 grafts were occluded (17/489; 3.5 %). Two of the grafts displayed malignant graft failure (a saphenous vein graft to the right coronary artery and a saphenous vein graft to the diagonal branch) (2 of 17 occluded grafts, and 2 of 489 studied grafts). Of the patent bypass grafts, 24 involved progression to occlusion in the proximal native coronary artery (19 saphenous vein grafts, 4 left internal thoracic artery grafts, and 1 right internal thoracic artery graft). Malignant graft failure was uncommon during short-term follow-up after CABG. At the same time, disease progression in the proximal native coronary artery from stenosis to occlusion following patent bypass grafting was relatively common, especially for vein grafts.

  15. Constitutive high expression of chromosomal beta-lactamase in Pseudomonas aeruginosa caused by a new insertion sequence (IS1669) located in ampD

    DEFF Research Database (Denmark)

    Bagge, N.; Ciofu, O.; Hentzer, Morten;


    resistant, constitutive beta-lactamase-producing variant contained no mutations in ampD, but a point mutation was observed in ampR, resulting in an Asp-135-->Asn change. An identical mutation of AmpR in Enterobacter cloacae has been reported to cause a 450-fold higher AmpC expression. However, in many...

  16. Differential Effects of Temperature on cAMP-induced Excitation, Adaptation, and Deadaptation of Adenylate and Guanylate Cyclase in Dictyostelium discoideum

    NARCIS (Netherlands)

    Haastert, Peter J.M. van


    Extracellular cAMP induces excitation of adenylate and guanylate cyclase in Dictyostelium discoideum. Continuous stimulation with cAMP leads to adaptation, while cells deadapt upon removal of the cAMP stimulus. Excitation of guanylate cyclase by cAMP has a lag time of ~1 s; excitation of adenylate c

  17. Bilateral Mooren's ulcer - Customised corneal graft with additional amniotic membrane graft. (United States)

    Bhandari, Vipul; Siddharthan, K S


    Mooren's ulcer (MU) is a rare and painful peripheral corneal ulceration which occurs in the absence of any associated scleritis, and any detectable systemic disease. A 60-year-old male patient was referred to us with bilateral peripheral corneal ulceration. Best corrected visual acuity (BCVA) in both eyes was counting finger at one metre. The right eye showed a 180° thinning with perforation at 8 o'clock position. The left eye showed a 360° thinning with central contact lens type cornea. After complete blood analysis we started the patient on cyclophosphamide orally along with high doses of oral steroids. A crescentic excision of the thinned cornea and crescentic customised corneal graft with additional amniotic membrane graft (AMG) was done first for the right eye and a 360° peripheral lamellar corneal graft with additional AMG for the left eye. The BCVA of RE was 1/60 improving to 6/36 with plus ten aphakic glasses and LE was 3/60. Hand fashioned full thickness crescentic customised corneal graft with additional AMG and a peripheral 360° lamellar corneal graft with additional AMG in these cases are a novel approach to Mooren's ulcer with gratifying results.

  18. Vv-AMP1, a ripening induced peptide from Vitis vinifera shows strong antifungal activity

    Directory of Open Access Journals (Sweden)

    Vivier Melané A


    Full Text Available Abstract Background Latest research shows that small antimicrobial peptides play a role in the innate defense system of plants. These peptides typically contribute to preformed defense by developing protective barriers around germinating seeds or between different tissue layers within plant organs. The encoding genes could also be upregulated by abiotic and biotic stimuli during active defense processes. The peptides display a broad spectrum of antimicrobial activities. Their potent anti-pathogenic characteristics have ensured that they are promising targets in the medical and agricultural biotechnology sectors. Results A berry specific cDNA sequence designated Vv-AMP1, Vitis vinifera antimicrobial peptide 1, was isolated from Vitis vinifera. Vv-AMP1 encodes for a 77 amino acid peptide that shows sequence homology to the family of plant defensins. Vv-AMP1 is expressed in a tissue specific, developmentally regulated manner, being only expressed in berry tissue at the onset of berry ripening and onwards. Treatment of leaf and berry tissue with biotic or abiotic factors did not lead to increased expression of Vv-AMP1 under the conditions tested. The predicted signal peptide of Vv-AMP1, fused to the green fluorescent protein (GFP, showed that the signal peptide allowed accumulation of its product in the apoplast. Vv-AMP1 peptide, produced in Escherichia coli, had a molecular mass of 5.495 kDa as determined by mass spectrometry. Recombinant Vv-AMP1 was extremely heat-stable and showed strong antifungal activity against a broad spectrum of plant pathogenic fungi, with very high levels of activity against the wilting disease causing pathogens Fusarium oxysporum and Verticillium dahliae. The Vv-AMP1 peptide did not induce morphological changes on the treated fungal hyphae, but instead strongly inhibited hyphal elongation. A propidium iodide uptake assay suggested that the inhibitory activity of Vv-AMP1 might be associated with altering the membrane

  19. NMR studies of the AMP-binding site and mechanism of adenylate kinase. (United States)

    Fry, D C; Kuby, S A; Mildvan, A S


    NMR has previously been used to determine the conformation of enzyme-bound MgATP and to locate the MgATP-binding site on adenylate kinase [Fry, D. C., Kuby, S. A., & Mildvan, A. S. (1985) Biochemistry 24, 4680-4694]. To determine the conformation and location of the other substrate, AMP, distances have been measured from Cr3+AMPPCP, a linear competitive inhibitor with respect to MgATP, to six protons and to the phosphorus atom of AMP on adenylate kinase, with the paramagnetic probe-T1 method. Time-dependent nuclear Overhauser effects (NOEs) have been used to measure five interproton distances on enzyme-bound AMP. These distances were used to determine the conformation of bound AMP in addition to its position with respect to metal-ATP. Enzyme-bound AMP exhibits a high anti-glycosyl torsional angle (chi = 110 +/- 10 degrees), a 3'-endo,2'-exo ribose pucker (delta = 105 +/- 10 degrees), and gauche-trans orientations about the C4'-C5' bond (gamma = 180 +/- 10 degrees) and the C5'-O5' bond (beta = 170 +/- 20 degrees). The distance from Cr3+ to the phosphorus of AMP is 5.9 +/- 0.3 A, indicating a reaction coordinate distance of approximately 3 A, which is consistent with an associative SN2 mechanism for the phosphoryl transfer. Ten intermolecular NOEs, from protons of the enzyme to those of AMP, were detected, indicating the proximity of at least three hydrophobic amino acids to bound AMP. These constraints, together with the conformation of AMP and the intersubstrate distances, were used to position AMP into the X-ray structure of adenylate kinase. The AMP binding site is found to be near (less than or equal to 4 A from) Leu-116, Arg-171, Val-173, Val-182, and Leu-190; all of these residues have been found to be invariant in muscle-type rabbit, calf, human, porcine [Kuby, S. A., Palmieri, R. H., Frischat, A., Fischer, A. H., Wu, L. H., Maland, L., & Manship, M. (1984) Biochemistry 23, 2393-2399], and chicken adenylate kinase [Kishi, F., Maruyama, M., Tanizawa, Y

  20. AmpC酶分类及检测的研究进展%Advance on Classification and Research of AmpC Enzyme

    Institute of Scientific and Technical Information of China (English)

    马艳红; 孙慧芳



  1. Evaluation of different graft material in type 1 tympanoplasty

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    Kshitij Patil


    Full Text Available Aims and Objective: The present study was undertaken to compare the results of various autogeneous tissues temporalis fascia, tragal perichondrium, and fascia lata as graft materials for the type 1 tympanoplasty. Materials and Methods: A total of 120 cases with large, subtotal and total perforation were considered in the study. Of the 120 cases, temporalis fascia graft was used in 60 cases (Group-I, tragal perichondrium graft in 40 cases (Group-II, and fascia lata graft in 20 cases (Group-III. The results were evaluated in the form of rate of graft success, hearing gain, and mean residual air-bone gap with respect to the graft materials. Results and Observation: A nonsignificant association was observed between the groups, that is, temporalis fascia (Group-I, tragal perichondrium (Group-II, and fascia lata (Group-III and the graft uptake. (P = 0.96 > 0.05 and air bone closure (χ2 = 2.908, P = 0.059 > 0.05. Conclusion: The graft take-up rate and Hearing improvement are similar for the different graft materials used. Size of the perforation doesn′t significantly influence the success rate of tympanoplasty as per our study. Normal translucent appearance of neotympanum in the postoperative period was seen only with temporalis fascia, while in tragal perichondrial and fascia lata grafts the neotympanum was whitish, thicker, and translucent to opaque.


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    E.S. Stolyarevich


    Full Text Available Rejection has always been one of the most important cause of late renal graft dysfunction. Aim of the study was to analyze the prevalence of different clinico-pathological variants of rejection that cause late graft dysfunction, and evaluate their impact on long-term outcome. Materials and methods. This is a retrospective study that analyzed 294 needle core biopsy specimens from 265 renal transplant recipients with late (48,8 ± 46,1 months after transplantation allograft dysfunction caused by late acute rejection (LAR, n = 193 or chronic rejection (CR, n = 78 or both (n = 23. C4d staining was performed by immunofl uorescence (IF on frozen sections using a standard protocol. Results. Peritubular capillary C4d deposition was identifi ed in 36% samples with acute rejection and in 62% cases of chronic rejection (including 67% cases of transplant glomerulopathy, and 50% – of isolated chronic vasculopathy. 5-year graft survival for LAR vs CR vs their combination was 47, 13 and 25%, respectively. The outcome of C4d– LAR was (p < 0,01 better than of C4d+ acute rejection: at 60 months graft survival for diffuse C4d+ vs C4d− was 33% vs 53%, respectively. In cases of chronic rejection C4d+ vs C4d– it was not statistically signifi cant (34% vs 36%. Conclusion. In long-term allograft biopsy C4d positivity is more haracteristic for chronic rejection than for acute rejection. Only diffuse C4d staining affects the outcome. C4d– positivity is associated with worse allograft survival in cases of late acute rejection, but not in cases of chronic rejection. 

  3. Coronary artery bypass grafting for Kawasaki disease

    Institute of Scientific and Technical Information of China (English)

    GUO Hong-wei; CHANG Qian; XU Jian-ping; SONG Yun-hu; SUN Han-song; HU Sheng-shou


    Background Kawasaki disease (KD) is the leading cause of pediatric ischemic heart disease. The incidence of serious coronary sequelae is low and about 2%-3% of patients with KD, but once myocardial infarction occurs in children, the mortality is quite high and 22% at the first infarction.This study aimed to evaluate the efficacy of coronary artery bypass grafting (CABG) in patients with KD.Methods Eight patients with a history of KD underwent CABG between October 1997 and July 2005. The number of bypass grafts placed was 2 to 4 per patient (mean 2.5±0.8). Various bypass grafts were used in patients, i.e. the left internal mammary artery (LIMA) in 3 patients, bilateral internal mammary artery (IMA) in 2 patients, LIMA plus gastroepiploic artery (GEA) in 1 patient and total saphenous vein grafts (SVGs) in 2 patients. The combined procedures included ventricular aneurysmectomy in 1 patient, mitral valve plasty in 1 and right coronary aneurysmectomy in 1. One patient was not able to wean from cardiopulmonary bypass (CPB), after being supported with intra-aortic balloon pump (IABP), the patient was weaned from CPB successfully.Results One patient died of low cardiac output syndrome and acute renal failure 19 days after operation. Other patients recovered and were discharged uneventfully. During the follow-up that ranged from 3 to 57 months (mean 27 months),clincal angina disappeared or improved. Cardiac function was in Class Ⅰ-Ⅱ (NYHA).Conclusion CABG is a safe and effective procedure for Kawasaki coronary artery disease. However long-term results need to be followed up.

  4. Graft selection in anterior cruciate ligament reconstruction. (United States)

    Miller, Suzanne L; Gladstone, James N


    Selecting the appropriate graft for ACL reconstruction depends on numerous factors including surgeon philosophy and experience, tissue availability (affected by anatomical anomalies or prior injury or surgery), and patient activity level and desires. Although the patella tendon autograft has the widest experience in the literature, and is probably the most commonly used graft source, this must be tempered with the higher reported incidences of potential morbidity and pitfalls associated with its use. The hamstring tendons are gaining increasing popularity, mostly due to reduced harvest morbidity and improved soft tissue fixation techniques, and many recent studies in the literature report equal results to BTB ACL reconstruction with respect to functional outcome and patient satisfaction. On the other hand, many of these studies report higher degrees of instrument (KT-100) tested laxity for hamstring reconstruction, and some have reported lower returns to preinjury levels of activity. One question that remains to be addressed is how closely objectively measured laxity tests correlate with subjectively assessed outcomes and ability to return to high levels of competitive sports. Allograft use, which decreased in popularity during the 1990s, appears to be undergoing a resurgence, with better sterilization processes and new graft sources (tibialis tendons), leading to increased availability and improved fixation techniques. The benefits of decreased surgical morbidity and easier rehabilitation must be weighed against the potential for greater failure of biologic incorporation, infection, and possibly slower return to activities. In our practice, for high-demand individuals (those playing cutting, pivoting, or jumping sports and skiing) BTB tends to be the graft of choice. For lower demand or older individuals, hamstring reconstructions will be performed. Allograft tissue will be used in older individuals (generally over 45 years old), those with signs of arthritis (and

  5. Improvement of tomato local varieties by grafting in organic farming (United States)

    Moreno, Marta M.; Villena, Jaime; Moreno, Carmen; García, Arántzazu M.; Mancebo, Ignacio; Meco, Ramón


    Grafting is the union of two or more pieces of living plant tissue that grow as a single plant. The early use of grafted vegetables was associated with protected cultivation which involves successive cropping (Lee et al., 2010). For this reason, in the past, grafting was used with vegetable crops to limit the effects of soil-borne diseases. However, the reasons for grafting as well as the kinds of vegetable grafted have increased considerably over the years. In tomato (Solanum lycopersicum L.), one of the most important horticultural crops in the world, the effect of grafting has also been widely studied. These effects on commercial tomato varieties can be summarized in increasing plant vigor and crop yield or inducing tolerance to abiotic stresses, although the effects on tomato fruit quality or on the sensory properties are not so patent (David et al., 2008). However, a few studies about the effect of grafting on local tomato varieties, which are especially recommended for organic production in spite of their lower yields in many cases, have been developed. In this work we evaluated the effect of grafting on tomato local varieties under organic management using vigorous commercial rootstocks, and aspects related to vigor, yield and tomato fruit composition were analyzed. In general terms, grafting increased the plant vigor, the crop yield and the fruit antioxidant content, although no modification of morphological fruit attributes was observed. Keywords: grafting, Solanum lycopersicum L., local varieties, organic farming. References: Davis A.R., Perkins-Veazie P., Hassell R., Levi A., King S.R., Zhang X. 2008. Grafting effects on vegetable quality. HortScience 43(6): 1670-1671. Lee J.M., Kubota C., Tsao S.J., Bie Z., Hoyos-Echevarría P., Morra L., Oda M. 2010. Current status of vegetable grafting: Diffusion, grafting techniques, automation. Scientia Horticulturae 127: 93-105.

  6. Dynamic, nondestructive imaging of a bioengineered vascular graft endothelium.

    Directory of Open Access Journals (Sweden)

    Bryce M Whited

    Full Text Available Bioengineering of vascular grafts holds great potential to address the shortcomings associated with autologous and conventional synthetic vascular grafts used for small diameter grafting procedures. Lumen endothelialization of bioengineered vascular grafts is essential to provide an antithrombogenic graft surface to ensure long-term patency after implantation. Conventional methods used to assess endothelialization in vitro typically involve periodic harvesting of the graft for histological sectioning and staining of the lumen. Endpoint testing methods such as these are effective but do not provide real-time information of endothelial cells in their intact microenvironment, rather only a single time point measurement of endothelium development. Therefore, nondestructive methods are needed to provide dynamic information of graft endothelialization and endothelium maturation in vitro. To address this need, we have developed a nondestructive fiber optic based (FOB imaging method that is capable of dynamic assessment of graft endothelialization without disturbing the graft housed in a bioreactor. In this study we demonstrate the capability of the FOB imaging method to quantify electrospun vascular graft endothelialization, EC detachment, and apoptosis in a nondestructive manner. The electrospun scaffold fiber diameter of the graft lumen was systematically varied and the FOB imaging system was used to noninvasively quantify the affect of topography on graft endothelialization over a 7-day period. Additionally, results demonstrated that the FOB imaging method had a greater imaging penetration depth than that of two-photon microscopy. This imaging method is a powerful tool to optimize vascular grafts and bioreactor conditions in vitro, and can be further adapted to monitor endothelium maturation and response to fluid flow bioreactor preconditioning.

  7. Immuohistochemical study on smooth muscle cell proliferation, phenotypic modulation, and extracellular matrix accumulation in venous arterial grafts in rabbits

    Institute of Scientific and Technical Information of China (English)

    ZHANG Wei-da; ZHU Hai-long


    due to ECM accumulation. Prolonged existence of the embryonic-type SMCs in the neointima may contribute to ECM accumulation and increase in the neointima thickness infinitely, which may predispose accelerated stenosis in the vein graft.

  8. Umbilical cord blood graft enhancement strategies: has the time come to move these into the clinic? (United States)

    Norkin, M; Lazarus, H M; Wingard, J R


    Umbilical cord blood (UCB) is an attractive stem cell graft option for patients who need allogeneic hematopoietic stem cell support, but lack a suitable HLA-matched donor. However, the limited number of hematopoietic progenitor cells in a single cord blood unit can lead to an increased risk of graft failure, delayed hematological recovery and prolonged immunosuppression, particularly in adult patients. Several strategies to overcome these potential limitations are being evaluated. In this review, we discuss promising ex vivo manipulations to enhance cord blood engraftment capacity such as culture of UCB cells with stimulatory cytokines and growth factors, mesenchymal cells, Notch ligand, copper chelators, prostaglandins, complement components, nicotinamide and CD26/DPPIV inhibitors. All these approaches are now in early clinical trials. However, despite the fact that several cord blood enhancement strategies have resulted in increased numbers of progenitor cells and faster neutrophil recovery, the ability of these techniques to significantly shorten engraftment time and permit the use of cord units with low numbers of total nucleated cells, or accomplish reliable engraftment with a single cord, have yet to be convincingly demonstrated. The ultimate clinical value of ex vivo cord blood expansion or manipulation has not been defined yet, and the current data do not permit predicting which technology will prove to be the optimal strategy. Nevertheless, expectations remain high that eventually ex vivo enhancement will be able to improve clinical outcomes and significantly extend the applicability of UCB transplantation.

  9. cAMP signaling in blood platelets - old friends and new players.

    Directory of Open Access Journals (Sweden)

    Zaher eRaslan


    Full Text Available Atherothrombosis, the pathology underlying numerous cardiovascular diseases, is a major cause of death globally. Hyperactive blood platelets play a key role in the atherothrombotic process through the release of inflammatory mediators and formation of thrombi. In healthy blood vessels, excessive platelet activation is restricted by endothelial-derived prostacyclin (PGI2 through cyclic adenosine-5’-monophosphate (cAMP and protein kinase A (PKA-dependent mechanisms. Elevation in intracellular cAMP is associated with the control of a number of distinct platelet functions including actin polymerisation, granule secretion, calcium mobilisation and integrin activation. Unfortunately, in atherosclerotic disease the protective effects of cAMP are compromised, which may contribute to pathological thrombosis. The cAMP signalling network in platelets is highly complex with the presence of multiple isoforms of adenylyl cyclase (AC, PKA and phosphodiesterases (PDE. However, a precise understanding of the relationship between specific AC, PKA and PDE isoforms, and how individual signalling substrates are targeted to control distinct platelet functions is still lacking. In other cells types, compartmentalisation of cAMP signalling has emerged as a key mechanism to allow precise control of specific cell functions. A-kinase anchoring proteins (AKAPs play an important role in this spatiotemporal regulation of cAMP signalling networks. Evidence of AKAP-mediated compartmentalisation of cAMP signalling in blood platelets has begun to emerge and is providing new insights into the regulation of platelet function. Dissecting the mechanisms that allow cAMP to control excessive platelet activity without preventing effective haemostasis may unleash the possibility of therapeutic targeting of the pathway to control unwanted platelet activity.

  10. Degradation of Polycyclic Aromatic Hydrocarbon Pyrene by Biosurfactant-Producing Bacteria Gordonia cholesterolivorans AMP 10



    Pyrene degradation and biosurfactant activity by a new strain identified as Gordonia cholesterolivorans AMP 10 were studied. The strain grew well and produced effective biosurfactants in the presence of glucose, sucrose, and crude oil. The biosurfactants production was detected by the decreased surface tension of the medium and emulsification activity.  Analysis of microbial growth parameters showed that AMP10 grew best at 50 µg mL-1 pyrene concentration, leading to 96 % degradation of pyrene...

  11. Cyclic AMP-inducible genes respond uniformly to seasonal lighting conditions in the rat pineal gland. (United States)

    Spessert, R; Gupta, B B P; Rohleder, N; Gerhold, S; Engel, L


    The encoding of photoperiodic information ensues in terms of the daily profile in the expression of cyclic AMP (cAMP)-inducible genes such as the arylalkylamine N-acetyltransferase (AA-NAT) gene that encodes the rate-limiting enzyme in melatonin formation. In the present study, we compared the influence of the photoperiodic history on the cAMP-inducible genes AA-NAT, inducible cyclic AMP early repressor (ICER), fos-related antigen-2 (FRA-2), mitogen-activated protein kinase phosphatase-1 (MKP-1), nerve growth factor inducible gene-A (NGFI-A) and nerve growth factor inducible gene-B (NGFI-B) in the pineal gland of rats. For this purpose, we monitored the daily profiles of each gene in the same pineal gland under a long (light/dark 16:8) and a short (light/dark 8:16) photoperiod by measuring the respective mRNA amounts by real-time polymerase chain reaction analysis. We found that, for all genes under investigation, the duration of increased nocturnal expression is lengthened and, in relation to light onset, the nocturnal rise is earlier under the long photoperiod (light/dark 16:8). Furthermore, with the exception of ICER, all other cAMP-inducible genes tend to display higher maximum expression under light/dark 8:16 than under light/dark 16:8. Photoperiod-dependent changes persist for all of the cAMP-inducible genes when the rats are kept for two cycles under constant darkness. Therefore, all cAMP-inducible genes are also influenced by the photoperiod of prior entrained cycles. Our study indicates that, despite differences regarding the expressional control and the temporal phasing of the daily profile, cAMP-inducible genes are uniformly influenced by photoperiodic history in the rat pineal gland.

  12. Effect of AMP on mRNA binding by yeast NAD+-specific isocitrate dehydrogenase. (United States)

    Anderson, Sondra L; Schirf, Virgil; McAlister-Henn, L


    Yeast mitochondrial NAD+-specific isocitrate dehydrogenase (IDH) has previously been shown to bind specifically to 5'-untranslated regions of yeast mitochondrial mRNAs, and transcripts containing these regions have been found to allosterically inhibit activity of the enzyme. This inhibition is relieved by AMP, an allosteric activator of this regulatory enzyme of the tricarboxylic acid cycle. We further investigated these enzyme/ligand interactions to determine if binding of RNA and AMP by IDH is competitive or independent. Gel mobility shift experiments indicated no effect of AMP on formation of an IDH/RNA complex. Similarly, sedimentation velocity ultracentrifugation experiments used to analyze interactions in solution indicated that AMP alone had little effect on the formation or stability of an RNA/IDH complex. However, when these sedimentation experiments were conducted in the presence of isocitrate, which has been shown to be essential for binding of AMP by IDH, the proportion of RNA sedimenting in a complex with IDH was significantly reduced by AMP. These results suggest that AMP can affect the binding of RNA by IDH but that this effect is apparent only in the presence of substrate. They also suggest that the catalytic activity of IDH in vivo may be subject to complex allosteric control determined by relative mitochondrial concentrations of mRNA, isocitrate, and AMP. We also found evidence for binding of 5'-untranslated regions of mitochondrial mRNAs by yeast mitochondrial NADP+-specific isocitrate dehydrogenase (IDP1) but not by the corresponding cytosolic isozyme (IDP2). However, this appears to be a nonspecific interaction since no evidence was obtained for any effect on the catalytic activity of IDP1.

  13. AmpC β-lactamases in nosocomial isolates of Klebsiella pneumoniae from India


    Gupta, Varsha; Kumarasamy, Karthikeyan; Gulati, Neelam; Garg, Ritu; Krishnan, Padma; Chander, Jagdish


    Background & objectives: AmpC β-lactamases are clinically significant since these confer resistance to cephalosporins in the oxyimino group, 7-α methoxycephalosporins and are not affected by available β-lactamase inhibitors. In this study we looked for both extended spectrum β-lactamases (ESBL) and AmpC β-lactamases in Klebsiella pneumoniae clinical isolates. Methods: One hundred consecutive, non-duplicate clinical isolates of K. pneumoniae collected over a period of one year (June 2008 - Jun...

  14. Cyclic AMP functions as a primary sexual signal in gametes of Chlamydomonas reinhardtii. (United States)

    Pasquale, S M; Goodenough, U W


    When Chlamydomonas reinhardtii gametes of opposite mating type are mixed together, they adhere by a flagella-mediated agglutination that triggers three rapid mating responses: flagellar tip activation, cell wall loss, and mating structure activation accompanied by actin polymerization. Here we show that a transient 10-fold elevation of intracellular cAMP levels is also triggered by sexual agglutination. We further show that gametes of a single mating type can be induced to undergo all three mating responses when presented with exogenous dibutyryl-cAMP (db-cAMP). These events are also induced by cyclic nucleotide phosphodiesterase inhibitors, which elevate endogenous cAMP levels and act synergistically with db-cAMP. Non-agglutinating mutants of opposite mating type will fuse efficiently in the presence of db-cAMP. No activation of mating events is induced by calcium plus ionophores, 8-bromo-cGMP, dibutyryl-cGMP, nigericin at alkaline pH, phorbol esters, or forskolin. H-8, an inhibitor of cyclic nucleotide-dependent protein kinase, inhibits mating events in agglutinating cells and antagonizes the effects of cAMP on non-agglutinating cells. Adenylate cyclase activity was detected in both the gamete cell body and flagella, with the highest specific activity displayed in flagellar membrane fractions. The flagellar membrane adenylate cyclase is preferentially stimulated by Mn++, unresponsive to NaF, GTP, GTP gamma S, AlF4-, and forskolin, and is inhibited by trifluoperazine. Cyclic nucleotide phosphodiesterase activity is also present in flagella. Our observations indicate that cAMP is a sufficient initial signal for all of the known mating reaction events in C. reinhardtii, and suggest that the flagellar cyclase and/or phosphodiesterase may be important loci of control for the agglutination-stimulated production of this signal.

  15. Cooperation between cAMP signalling and sulfonylurea in insulin secretion. (United States)

    Shibasaki, T; Takahashi, T; Takahashi, H; Seino, S


    Although glucose is physiologically the most important regulator of insulin secretion, glucose-induced insulin secretion is modulated by hormonal and neural inputs to pancreatic β-cells. Most of the hormones and neurotransmitters evoke intracellular signals such as cAMP, Ca²⁺ , and phospholipid-derived molecules by activating G protein-coupled receptors (GPCRs). In particular, cAMP is a key second messenger that amplifies insulin secretion in a glucose concentration-dependent manner. The action of cAMP on insulin secretion is mediated by both protein kinase A (PKA)-dependent and Epac2A-dependent mechanisms. Many of the proteins expressed in β-cells are phosphorylated by PKA in vitro, but only a few proteins in which PKA phosphorylation directly affects insulin secretion have been identified. On the other hand, Epac2A activates the Ras-like small G protein Rap in a cAMP-dependent manner. Epac2A is also directly activated by various sulfonylureas, except for gliclazide. 8-pCPT-2'-O-Me-cAMP, an Epac-selective cAMP analogue, and glibenclamide, a sulfonylurea, synergistically activate Epac2A and Rap1, whereas adrenaline, which suppresses cAMP production in pancreatic β-cells, blocks activation of Epac2A and Rap1 by glibenclamide. Thus, cAMP signalling and sulfonylurea cooperatively activate Epac2A and Rap1. This interaction could account, at least in part, for the synergistic effects of incretin-related drugs and sulfonylureas in insulin secretion. Accordingly, clarification of the mechanism of Epac2A activation may provide therapeutic strategies to improve insulin secretion in diabetes.

  16. NMr studies of the AMP binding site and mechanism of adenylate kinase

    Energy Technology Data Exchange (ETDEWEB)

    Kuby, S.A.; Fry, D.C.; Mildvan, A.S.


    The authors recently located by NMR the MgATP binding site on adenylate kinase correcting the proposed location for this site based on X-ray studies of the binding of salicylate. To determine the conformation and location of the other substrate, they have determined distances from Cr/sup 3 +/ AMPPCP to 6 protons and to the phosphorus atom of AMP on adenylate kinase using the paramagnetic-probe-T/sub 1/ method. They have also used time-dependent NOEs to measure five interproton distances on AMP, permitting evaluation of the conformation of enzyme-bound AMP and its position with respect to metal-ATP. Enzyme-bound AMP exhibits a high-anti glycosyl torsional angle (X = 110/sup 0/), a 3'-endo sugar pucker (delta = 105/sup 0/), and a gauche-trans orientation about the C/sub 4/'-C/sub 5/' bond (..gamma.. = 180/sup 0/). The distance from Cr/sup 3 +/ to the phosphorus of AMP is 6.4 +/- 0.3 A, indicating a reaction coordinate distance of greater than or equal to A which is consistent with an associative SN2 mechanism for the phosphoryl transfer. Ten intermolecular NOEs, from protons of the enzyme to those of AMP were detected. These constraints, together with the conformation of AMP and the X-ray structure of the enzyme, suggest proximity (less than or equal to A) of AMP to leu 116, arg 171, val 173, gln 185, thr 188, and asp 191.

  17. Guanine Nucleotides Modulate Cell Surface cAMP-Binding Sites in Membranes from Dictyostelium discoideum

    NARCIS (Netherlands)

    Haastert, Peter J.M. van


    D. discoideum contains kinetically distinguishable cell surface cAMP binding sites. One class, S, is slowly dissociating and has high affinity for cAMP (Kd = 15 nM, t½ = 15 s). A second class is fast dissociating (t½ about 1 s) and is composed of high affinity binding sites H (Kd ≈ 60 nM), and low a

  18. A Patient with Recurrent Arteriovenous Graft Thrombosis. (United States)

    Allon, Michael


    Arteriovenous grafts (AVGs) are prone to frequent thrombosis that is superimposed on underlying hemodynamically significant stenosis, most commonly at the graft-vein anastomosis. There has been great interest in detecting AVG stenosis in a timely fashion and performing preemptive angioplasty, in the belief that this will prevent AVG thrombosis. Three surveillance methods (static dialysis venous pressure, flow monitoring, and duplex ultrasound) can detect AVG stenosis. Whereas observational studies have reported that surveillance with preemptive angioplasty substantially reduces AVG thrombosis, randomized clinical trials have failed to confirm such a benefit. There is a high frequency of early AVG restenosis after angioplasty caused by aggressive neointimal hyperplasia resulting from vascular injury. Stent grafts prevent AVG restenosis better than balloon angioplasty, but they do not prevent AVG thrombosis. Several pharmacologic interventions to prevent AVG failure have been evaluated in randomized clinical trials. Anticoagulation or aspirin plus clopidogrel do not prevent AVG thrombosis, but increase hemorrhagic events. Treatment of hyperhomocysteinemia does not prevent AVG thrombosis. Dipyridamole plus aspirin modestly decreases AVG stenosis or thrombosis. Fish oil substantially decreases the frequency of AVG stenosis and thrombosis. In patients who have exhausted all options for vascular access in the upper extremities, thigh AVGs are a superior option to tunneled internal jugular vein central vein catheters (CVCs). An immediate-use AVG is a reasonable option in patients with recurrent CVC dysfunction or infection. Tunneled femoral CVCs have much worse survival than internal jugular CVCs.

  19. Grafting of protein-protein binding sites

    Institute of Scientific and Technical Information of China (English)


    A strategy for grafting protein-protein binding sites is described. Firstly, key interaction residues at the interface of ligand protein to be grafted are identified and suitable positions in scaffold protein for grafting these key residues are sought. Secondly, the scaffold proteins are superposed onto the ligand protein based on the corresponding Ca and Cb atoms. The complementarity between the scaffold protein and the receptor protein is evaluated and only matches with high score are accepted. The relative position between scaffold and receptor proteins is adjusted so that the interface has a reasonable packing density. Then the scaffold protein is mutated to corresponding residues in ligand protein at each candidate position. And the residues having bad steric contacts with the receptor proteins, or buried charged residues not involved in the formation of any salt bridge are mutated. Finally, the mutated scaffold protein in complex with receptor protein is co-minimized by Charmm. In addition, we deduce a scoring function to evaluate the affinity between mutated scaffold protein and receptor protein by statistical analysis of rigid binding data sets.

  20. Patient's Perception About Coronary Artery Bypass Grafting

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    Kelminda Maria Bulhões Mendonça


    Full Text Available ABSTRACT OBJECTIVE: The diagnosis of coronary artery disease referred for heart surgery has an important psychological component. The purpose of this study was to access the difficulties experienced by individuals awaiting coronary artery bypass grafting and to determine strategies that facilitate adaptation to a new lifestyle, modified by the disease. METHODS: A qualitative, exploratory study involving patients admitted to a university teaching hospital in the city of Salvador, Bahia, Brazil, awaiting coronary artery bypass grafting. Semi-structured interviews were performed in accordance with a previously defined script based on the study objective. Each transcription was read in its entirety to verify the representativeness, homogeneity and pertinence of the data obtained (pre-analysis, followed by separation of categories of analysis. RESULTS: The descriptions of this study show that patients admitted to the completion of coronary artery bypass grafting experience a wide range of psychological difficulties, considering that surgery acquires interpretations that vary according to individuals' subjectivity. The patients recognized the benefit of being able to discuss their feelings as a means of diminishing their fear and anxiety. CONCLUSION: Helping patients find resources to confront more positively the daily hospitalization is an important aspect for the health care professionals who assist them. This goal can be achieved through modification of the biomedical model of care for a biopsychosocial view. The investment of time and attention is of fundamental importance and aims to overcome existing deficiencies that interfere with the outcome of patients after cardiac surgery.