Intra-arterial infusion of prostaglandin E1 in normal subjects and patients with peripheral arterial disease

DEFF Research Database (Denmark)

Nielsen, P E; Nielsen, S L; Holstein, P

1976-01-01

Acute vasodilatation was produced by infusion of prostaglandin E1 (PGE1) in the femoral artery in 6 patients with occlusive arterial disease of the legs and in 3 normal subjects. The effect on blood flow and on blood pressure was measured at different segments of the leg with the strain gauge...

Prostaglandin E1 and prostaglandin F2 alpha in exudate in nickel allergy

DEFF Research Database (Denmark)

Lerche, A; Bisgaard, H; Kassis, V

1989-01-01

Ten nickel-allergic patients and 5 healthy control subjects participated in a study of the kinetics of the flux and concentration of migrated leukocytes and extracellular PGE1 and PGF2 alpha during a 48 h period, using a skin chamber technique. The patients were provided with two skin chambers, one...... with and one without nickel challenge. A higher flux of leukocytes, PGE1 and PGF2 alpha was observed during the second day of allergen exposure, while the concentrations probably due to dilution were unchanged or diminished, indicating an unspecific role of the prostaglandins during the contact allergic...

Stimulation of prostaglandin E2 production by phorbol esters and epidermal growth factor in porcine thyroid cells

International Nuclear Information System (INIS)

Kasai, K.; Hiraiwa, M.; Emoto, T.; Akimoto, K.; Takaoka, T.; Shimoda, S.I.

1987-01-01

Effects of phorbol esters and epidermal growth factor (EGF) on prostaglandin E 2 production by cultured porcine thyroid cells were examined. Both phorbol 12-myristate 13-acetate (PMA) and EGF stimulated prostaglandin E 2 production by the cells in dose related fashion. PMA stimulated prostaglandin E 2 production over fifty-fold with the dose of 10 -7 M compared with control. EGF (10 -7 M) also stimulated it about ten-fold. The ED 50 values of PMA and EGF were respectively around 1 x 10 -9 M and 5 x 10 -10 M. Thyroid stimulating hormone (TSH), however, did not stimulate prostaglandin E 2 production from 1 to 24-h incubation. The release of radioactivity from [ 3 H]-arachidonic acid prelabeled cells was also stimulated by PMA and EGF, but not by TSH. These results indicate that both PMA and EGF are potent stimulators of prostaglandin E 2 production, associated with the activity to stimulate arachidonic acid release in porcine thyroid cells. 36 references, 2 figures, 1 table

Role of the Prostaglandin E2 EP1 Receptor in Traumatic Brain Injury

Science.gov (United States)

Glushakov, Alexander V.; Fazal, Jawad A.; Narumiya, Shuh; Doré, Sylvain

2014-01-01

Brain injuries promote upregulation of so-called proinflammatory prostaglandins, notably prostaglandin E2 (PGE2), leading to overactivation of a class of its cognate G-protein-coupled receptors, including EP1, which is considered a promising target for treatment of ischemic stroke. However, the role of the EP1 receptor is complex and depends on the type of brain injury. This study is focused on the investigation of the role of the EP1 receptor in a controlled cortical impact (CCI) model, a preclinical model of traumatic brain injury (TBI). The therapeutic effects of post-treatments with a widely studied EP1 receptor antagonist, SC-51089, were examined in wildtype and EP1 receptor knockout C57BL/6 mice. Neurological deficit scores (NDS) were assessed 24 and 48 h following CCI or sham surgery, and brain immunohistochemical pathology was assessed 48 h after surgery. In wildtype mice, CCI resulted in an obvious cortical lesion and localized hippocampal edema with an associated significant increase in NDS compared to sham-operated animals. Post-treatments with the selective EP1 receptor antagonist SC-51089 or genetic knockout of EP1 receptor had no significant effects on cortical lesions and hippocampal swelling or on the NDS 24 and 48 h after CCI. Immunohistochemistry studies revealed CCI-induced gliosis and microglial activation in selected ipsilateral brain regions that were not affected by SC-51089 or in the EP1 receptor-deleted mice. This study provides further clarification on the respective contribution of the EP1 receptor in TBI and suggests that, under this experimental paradigm, the EP1 receptor would have limited effects in modulating acute neurological and anatomical pathologies following contusive brain trauma. Findings from this protocol, in combination with previous studies demonstrating differential roles of EP1 receptor in ischemic, neurotoxic, and hemorrhagic conditions, provide scientific background and further clarification of potential therapeutic

Utilization of a single antiserum for the direct radioimmunoassay of prostaglandins E and F in semen and prostaglandin F in amniotic fluid

International Nuclear Information System (INIS)

Clarke, A.H.; Ing, R.M.Y.; Jones, W.R.; Llewellyn-Jones, D.; Shutt, D.A.

1974-01-01

Antibodies to both prostaglandin F (PGF) and prostaglandin E (PGE) were raised in rabbits after they were immunized with prostaglandin F/sub 2a/ conjugated to bovine serum albumin (PGF/sub 2a/--BSA). The antisera were group specific although the antibodies to the F group of prostaglandins showed greater specificity than those to the E group. The antisera were sufficiently specific however to allow the direct radioimmunoassay of PGF and PGE in human semen and PGF in amniotic fluid during induced abortion. Specificity of the direct radioimmunoassay was checked by chromatographic separation of the prostaglandins prior to analysis. Estimation of the prostaglandins in the semen of 30 men attending the infertility clinic showed that 19 of the men had normal semen levels of PGE and PGF of 68 +- 7 (SE) and 6.0 +- 0.6 μg/ml respectively, as compared with data on normal fertile males, whilst the other 11 men had lower levels of 16 +- 2 (SE) and 0.8 +- 0.1 μg/ml respectively. Application of the method to amniotic fluid showed that the PGF concentration in amniotic fluid during the induction of abortion with extra-ovular saline increased from less than 0.6 ng/ml to 6.4 ng/ml when the induction-abortion intervals ranged from 6 to 48 hours. (U.S.)

Prostaglandin E and the local immune response in chronic periodontal disease

International Nuclear Information System (INIS)

Loening, T.; Albers, H.-K.; Lisboa, B.P.; Burkhardt, A.; Caselitz, J.

1980-01-01

The local immune reaction of progressive chronic periodontal disease may be particularly influenced by macrophages and macrophage-derived factors. Among these substances the prostaglandins and lysosomal enzymes may play an important pathogenetic role. Parallel immunohistochemical and radioimmunological studies were done to investigate the relatiships of the immune-competent cells and the inflammatory mediators in gingival tissues. The radioimmunological analysis revealed that prostaglandin E increases markedly in the established gingival lesions. Immunohistochemically prostaglandin E was mainly localized within macrophage-like cells. Cytoplasmic lysozyme could be detected in these cells, too. On the other hand, the B-cell response is the prominent feature in established chronic periodontal disease. However, there is apparently a disturbed B-cell reaction as indicated by the irregular IgG-subclass pattern and by the production of mainly monomeric IgA. The possible interactions of macrophages and especially B-cells via prostaglandin E-mediated mechanisms are discussed. (author)

Inhibition of food stimulated acid secretion by misoprostol, an orally active synthetic E1 analogue prostaglandin.

OpenAIRE

Ramage, J K; Denton, A; Williams, J G

1985-01-01

The effect of 200 micrograms misoprostol (a synthetic prostaglandin E1 analogue) on food stimulated intragastric acidity has been monitored over a 9 h period in 16 normal volunteers. Misoprostol caused a significant inhibition of intragastric acidity for 2 h post-dosing, but no significant effect was seen thereafter on either basal or food stimulated acidity.

Preferential binding of growth inhibitory prostaglandins by the target protein of a carcinogen

Energy Technology Data Exchange (ETDEWEB)

Khan, S.H.; Sorof, S. (Fox Chase Cancer Center, Philadelphia, PA (United States))

1990-12-01

Liver fatty acid binding protein (L-FABP) is the principal target protein of the hepatic carcinogen N-(2-fluorenyl)acetamide (2-acetylaminofluorene) in rat liver. In addition, the cyclopentenone prostaglandins (PG), PGA, PGJ{sub 2}, and {Delta}{sup 12}-PGJ{sub 2}, inhibit the growth of many cell types in vitro. This report describes the preferential binding of the growth inhibitory prostaglandins by L-FABP and the reversible inhibition of thymidine incorporation into DNA by PGA{sub 2} and {Delta}{sup 12}-PGJ{sub 2} in primary cultures of purified rat hepatocytes. As a model ligand, ({sup 3}H)PGA{sub 1} bound to L-FABP specifically, reversibly, rapidly, and with high affinity. Its dissociation constants were 134 nM (high affinity) and 3.6 {mu}M (low affinity). The high-affinity finding of ({sup 3}H)PGA{sup 1} correlated with their growth inhibitory activities reported previously and here. The in vitro actions of L-FABP are compatible with those of a specific and dissociable carrier of growth inhibitory prostaglandins in rat hepatocytes and suggest that the carcinogen may usurp the cellular machinery of the growth inhibitory prostaglandins.

Prostaglandin E2 release from dermis regulates sodium permeability of frog skin epithelium

DEFF Research Database (Denmark)

Rytved, Klaus A.; Brodin, Birger; Nielsen, Robert

1995-01-01

Arachidonic acid, cAMP, epithelium, frog skin, intracellular calcium, prostaglandin E*U2, sodium transport, tight epithelium.......Arachidonic acid, cAMP, epithelium, frog skin, intracellular calcium, prostaglandin E*U2, sodium transport, tight epithelium....

Reversibility of cortical hyperostosis following long-term prostaglandin E1 therapy in infants with ductus-dependent congenital heart disease

DEFF Research Database (Denmark)

Høst, A; Halken, S; Andersen, P E

1988-01-01

Two neonates with complex cyanotic congenital heart disease, receiving long-term prostaglandin E1 infusion, for 59 and 78 days respectively, demonstrated significant radiographic changes of symmetric cortical hyperostosis of the long bones. Bone biopsies from one of the patients elucidated...

Raman E sub 1 , E sub 1 + DELTA sub 1 resonance in nonstressed quantum dots of germanium

CERN Document Server

Talochkin, A B; Efanov, A V; Kozhemyako, I G; Shumskij, V N

2001-01-01

The Raman light scattering on the optical phonons in the nonstressed Ge quantum dots, obtained in the GaAs/ZnSe/Ge/ZnSe structures is studied through the molecular-beam epitaxy. The E sub 1 , E sub 1 + DELTA sub 1 resonance energy shift, connected with quantization of the electron and hole states spectrum in the quantum dots is observed. Application of the simplest localization model with an account of the Ge electron states spectrum made it possible to explain the observed peculiarities

The Effect of Thyroid Hormone, Prostaglandin E2, and Calcium Gluconate on Orthodontic Tooth Movement and Root Resorption in Rats.

Science.gov (United States)

Seifi, Massoud; Hamedi, Roya; Khavandegar, Zohre

2015-03-01

A major objective of investigators is to clarify the role of metabolites in achievement of maximum tooth movement with minimal root damage during orthodontic tooth movement (OTM). The aim of this study was to determine the effect of administration of thyroid hormone, prostaglandin E2, and calcium on orthodontic tooth movement and root resorption in rats. Sixty four male Wistar rats were randomly divided into 8 groups of eight rats each: 1- 20µg/kg thyroxine was injected in traperitoneally after installation of the orthodontic appliance.  2- 0.1 ml of 1 mg/ml prostaglandin E2 was injected submucosally.  3- 10% (200 mg/kg) calcium gluconate was injected.  4- Prostaglandin E2 was injected submucosally and 10% calcium was injected intraperitoneally.  5- Thyroxine was injected intraperitoneally and prostaglandin E2 was injected submucosally.  6- 20µg/kg thyroxine with calcium was injected. 7- Prostaglandin E2 was injected submucosally with calcium and thyroxine.  8- Distilled water was used in control group. The orthodontic appliances comprised of a NiTi closed coil were posteriorly connected to the right first molar and anteriorly to the upper right incisor. OTM was measured with a feeler gauge. The mid-mesial root of the first molar and the adjacent tissues were histologically evaluated. The Data were analyzed by one-way ANOVA and Student-Newman-Keuls test. The highest mean OTM was observed in the thyroxine and prostaglandin E2 group (Mean±SD = 0.7375±0.1359 mm) that was significantly different (proot resorption was observed between the prostaglandin E2 (0.0192±0.0198 mm(2)) and the other groups. It seems that the combination of thyroxine and prostaglandin E2, with a synergistic effect, would decrease the root resorption and increase the rate of orthodontic tooth movement in rats.

Induction of human microsomal prostaglandin E synthase 1 by activated oncogene RhoA GTPase in A549 human epithelial cancer cells

Energy Technology Data Exchange (ETDEWEB)

Choi, Hye Jin [Laboratory of Systems Mucosal Biomodulation, Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Lee, Dong-Hyung [Department of Obstetrics and Gynecology, Medical Research Institute, Pusan National University, Busan (Korea, Republic of); Park, Seong-Hwan; Kim, Juil; Do, Kee Hun [Laboratory of Systems Mucosal Biomodulation, Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan (Korea, Republic of); An, Tae Jin; Ahn, Young Sup; Park, Chung Berm [Department of Herbal Crop Research, NIHHS, RDA, Eumseong (Korea, Republic of); Moon, Yuseok, E-mail: moon@pnu.edu [Laboratory of Systems Mucosal Biomodulation, Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Medical Research Institute and Research Institute for Basic Sciences, Pusan National University, Busan (Korea, Republic of)

2011-09-30

Highlights: {yields} As a target of oncogene RhoA-linked signal, a prostaglandin metabolism is assessed. {yields} RhoA activation increases PGE{sub 2} levels and its metabolic enzyme mPGES-1. {yields} RhoA-activated NF-{kappa}B and EGR-1 are positively involved in mPGES-1 induction. -- Abstract: Oncogenic RhoA GTPase has been investigated as a mediator of pro-inflammatory responses and aggressive carcinogenesis. Among the various targets of RhoA-linked signals, pro-inflammatory prostaglandin E{sub 2} (PGE{sub 2}), a major prostaglandin metabolite, was assessed in epithelial cancer cells. RhoA activation increased PGE{sub 2} levels and gene expression of the rate-limiting PGE{sub 2} producing enzymes, cyclooxygenase-2 and microsomal prostaglandin E synthase 1 (mPGES-1). In particular, human mPGES-1 was induced by RhoA via transcriptional activation in control and interleukin (IL)-1{beta}-activated cancer cells. To address the involvement of potent signaling pathways in RhoA-activated mPGES-1 induction, various signaling inhibitors were screened for their effects on mPGES-1 promoter activity. RhoA activation enhanced basal and IL-1{beta}-mediated phosphorylated nuclear factor-{kappa}B and extracellular signal-regulated kinase1/2 proteins, all of which were positively involved in RhoA-induced gene expression of mPGES-1. As one potent down-stream transcription factor of ERK1/2 signals, early growth response gene 1 product also mediated RhoA-induced gene expression of mPGES-1 by enhancing transcriptional activity. Since oncogene-triggered PGE{sub 2} production is a critical modulator of epithelial tumor cells, RhoA-associated mPGES-1 represents a promising chemo-preventive or therapeutic target for epithelial inflammation and its associated cancers.

Effect of synthetic prostaglandin E1 analog on gastric emptying of meals in man.

Science.gov (United States)

Moore, J G; Alazraki, N; Clay, G D

1986-01-01

Forty-five subjects with healed duodenal ulcer were administered either a placebo or a low-dose or high-dose regimen of misoprostol, a synthetic PGE1 analog, in a double-blind, random, parallel-group design to assess the effect of this prostaglandin compound on the gastric emptying of liquid-solid meals. A dual-radionuclide technique to measure liquid- and solid-phase gastric emptying rates of physiological meals by external gamma camera imaging was used. All subjects had a pretreatment control (baseline) evaluation, followed one week later by a treatment-influenced emptying study. The results demonstrated that misoprostol did not significantly alter gastric emptying of either liquids or solids; however, these results cannot be extrapolated to other prostaglandin compounds because of the diverse and sometimes paradoxical effects of different prostaglandins on gastric motility.

Prostaglandin E2 regulates hematopoietic stem cell

International Nuclear Information System (INIS)

Wang Yingying; Zhou Daohong; Meng Aimin

2013-01-01

Prostaglandin E2 (PGE2) is a bioactive lipid molecule produced by cyclooxygenase (COX), which plays an important role on hematopoiesis. While it can block differentiation of myeloid progenitors but enhance proliferation of erythroid progenitors. Recent research found that PGE2 have the effects on hematopoietic stem cell (HSC) function and these effects were independent from effects on progenitor cells. Exposure of HSC cells to PGE2 in vitro can increase homing efficiency of HSC to the murine bone marrow compartment and decrease HSC apoptosis, meanwhile increase long-term stem cell engraftment. In-vivo treatment with PGE2 expands short-term HSC and engraftment in murine bone marrow but not long-term HSC.In addition, PGE2 increases HSC survival after radiation injury and enhance hematopoietic recovery, resulting maintains hematopoietic homeostasis. PGE2 regulates HSC homeostasis by reactive oxygen species and Wnt pathway. Clinical beneficial of 16, 16-dimethyl-prostaglandin E2 treatment to enhance engraftment of umbilical cord blood suggest important improvements to therapeutic strategies. (authors)

mPGES-1-derived prostaglandin E2 stimulates Stat3 to promote podocyte apoptosis.

Science.gov (United States)

Yu, Jing; Wu, Yimei; Wang, Lu; Zhang, Wen; Xu, Man; Song, Jiayu; Fu, Yu; Cui, Yiyun; Gong, Wei; Li, Shuzhen; Xia, Weiwei; Huang, Songming; Zhang, Aihua; Jia, Zhanjun

2017-11-01

We previously reported that microsomal prostaglandin E synthase-1 (mPGES-1) contributed to adriamycin (Adr)-induced podocyte apoptosis. However, the molecular mechanism remains unclear. Here we studied the role of mPGES-1/PGE2 cascade in activating Stat3 signaling and the contribution of Stat3 in PGE2- and Adr-induced podocyte apoptosis. In murine podocytes, PGE2 dose- and time-dependently increased the phosphorylation of Stat3 in line with the enhanced cell apoptosis and reduced podocyte protein podocin. In agreement with the increased Stat3 phosphorylation, Stat3-derived cytokines including IL-6, IL-17, MCP-1, and ICAM-1 were significantly upregulated following PGE2 treatment. By application of a specific Stat3 inhibitor S3I-201, PGE2-induced podocyte apoptosis was largely abolished in parallel with a blockade of podocin reduction. Next, we observed that Adr treatment also enhanced p-Stat3 and activated mPGES-1/PGE2 cascade. Blockade of Stat3 by S3I-201 significantly ameliorated Adr-induced cell apoptosis and podocin reduction. More interestingly, silencing mPGES-1 in podocytes by mPGES-1 siRNA blocked Adr-induced increments of Stat-3 phosphorylation, PGE2 production, and Stat3-derived inflammatory cytokines. Taken together, this study suggested that mPGES-1-derived PGE2 could activate Stat3 signaling to promote podocyte apoptosis. Targeting mPGES-1/PGE2/Stat3 signaling might be a potential strategy for the treatment of podocytopathy.

The Kallikrein-Kinin System in Bartter's Syndrome and Its Response to Prostaglandin Synthetase Inhibition

Science.gov (United States)

Vinci, Joseph M.; Gill, John R.; Bowden, Robert E.; Pisano, John J.; Izzo, Joseph L.; Radfar, Nazam; Taylor, Addison A.; Zusman, Randall M.; Bartter, Frederic C.; Keiser, Harry R.

1978-01-01

The kallikrein-kinin system was characterized in seven patients with Bartter's syndrome on constant metabolic regimens before, during, and after treatment with prostaglandin synthetase inhibitors. Patients with Bartter's syndrome had high values for plasma bradykinin, plasma renin activity (PRA), urinary kallikrein, urinary immunoreactive prostaglandin E excretion, and urinary aldosterone; urinary kinins were subnormal and plasma prekallikrein was normal. Treatment with indomethacin or ibuprofen which decreased urinary immunoreactive prostaglandin E excretion by 67%, decreased mean PRA (patients recumbent) from 17.3±5.3 (S.E.M.) ng/ml per h to 3.3±1.1 ng/ml per h, mean plasma bradykinin (patients recumbent) from 15.4±4.4 ng/ml to 3.9±0.9 ng/ml, mean urinary kallikrein excretion from 24.8±3.2 tosyl-arginine-methyl ester units (TU)/day to 12.4±2.0 TU/day, but increased mean urinary kinin excretion from 3.8±1.3 μg/day to 8.5±2.5 μg/day. Plasma prekallikrein remained unchanged at 1.4 TU/ml. Thus, with prostaglandin synthetase inhibition, values for urinary kallikrein and kinin and plasma bradykinin returned to normal pari passu with changes in PRA, in aldosterone, and in prostaglandin E. The results suggest that, in Bartter's syndrome, prostaglandins mediate the low urinary kinins and the high plasma bradykinin, and that urinary kallikrein, which is aldosterone dependent, does not control kinin excretion. The high plasma bradykinin may be a cause of the pressor hyporesponsiveness to angiotensin II which characterizes the syndrome. PMID:96139

Prostaglandin E2 stimulates Fas ligand expression via the EP1 receptor in colon cancer cells.

LENUS (Irish Health Repository)

O'Callaghan, G

2012-02-03

Fas ligand (FasL\\/CD95L) is a member of the tumour necrosis factor superfamily that triggers apoptosis following crosslinking of the Fas receptor. Despite studies strongly implicating tumour-expressed FasL as a major inhibitor of the anti-tumour immune response, little is known about the mechanisms that regulate FasL expression in tumours. In this study, we show that the cyclooxygenase (COX) signalling pathway, and in particular prostaglandin E(2) (PGE(2)), plays a role in the upregulation of FasL expression in colon cancer. Suppression of either COX-2 or COX-1 by RNA interference in HCA-7 and HT29 colon tumour cells reduced FasL expression at both the mRNA and protein level. Conversely, stimulation with PGE(2) increased FasL expression and these cells showed increased cytotoxicity against Fas-sensitive Jurkat T cells. Prostaglandin E(2)-induced FasL expression was mediated by signalling via the EP1 receptor. Moreover, immunohistochemical analysis using serial sections of human colon adenocarcinomas revealed a strong positive correlation between COX-2 and FasL (r=0.722; P<0.0001) expression, and between EP1 receptor and FasL (r=0.740; P<0.0001) expression, in the tumour cells. Thus, these findings indicate that PGE(2) positively regulates FasL expression in colon tumour cells, adding another pro-neoplastic activity to PGE(2).

Prevotella intermedia induces prostaglandin E2 via multiple signaling pathways.

Science.gov (United States)

Guan, S-M; Fu, S-M; He, J-J; Zhang, M

2011-01-01

Prostaglandin E(2) (PGE(2)) plays important roles in the bone resorption of inflammatory diseases such as rheumatoid arthritis and periodontitis via specific prostaglandin receptors (i.e., EP1-EP4). In this study, the authors examined whether Prevotella intermedia regulates PGE(2) production and EP expression in human periodontal ligament fibroblasts (hPDLs); they also explored the potential signaling pathways involved in PGE(2) production. P. intermedia induced PGE(2) production and cyclooxygenase-2 (COX-2) expression in a dose- and time-dependent manner. Indomethacin and NS-398 completely abrogated the P. intermedia-induced PGE(2) production without modulating COX-2 expression. Specific inhibitors of extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, phosphatidylinositol 3-kinase, and protein kinase C--but not c-AMP and protein kinase A--significantly attenuated the P. intermedia-induced COX-2 and PGE(2) expression. P. intermedia reduced EP1 expression in a concentration- and time-dependent manner. The results indicate that the COX-2-dependent induction of PGE(2) by P. intermedia in hPDLs is mediated by multiple signaling pathways.

Prostaglandins in Cancer Cell Adhesion, Migration, and Invasion

Directory of Open Access Journals (Sweden)

David G. Menter

2012-01-01

Full Text Available Prostaglandins exert a profound influence over the adhesive, migratory, and invasive behavior of cells during the development and progression of cancer. Cyclooxygenase-2 (COX-2 and microsomal prostaglandin E2 synthase-1 (mPGES-1 are upregulated in inflammation and cancer. This results in the production of prostaglandin E2 (PGE2, which binds to and activates G-protein-coupled prostaglandin E1-4 receptors (EP1-4. Selectively targeting the COX-2/mPGES-1/PGE2/EP1-4 axis of the prostaglandin pathway can reduce the adhesion, migration, invasion, and angiogenesis. Once stimulated by prostaglandins, cadherin adhesive connections between epithelial or endothelial cells are lost. This enables cells to invade through the underlying basement membrane and extracellular matrix (ECM. Interactions with the ECM are mediated by cell surface integrins by “outside-in signaling” through Src and focal adhesion kinase (FAK and/or “inside-out signaling” through talins and kindlins. Combining the use of COX-2/mPGES-1/PGE2/EP1-4 axis-targeted molecules with those targeting cell surface adhesion receptors or their downstream signaling molecules may enhance cancer therapy.

Microsomal Prostaglandin E Synthase-1 Facilitates an Intercellular Interaction between CD4⁺ T Cells through IL-1β Autocrine Function in Experimental Autoimmune Encephalomyelitis.

Science.gov (United States)

Takemiya, Takako; Takeuchi, Chisen; Kawakami, Marumi

2017-12-19

Microsomal prostaglandin synthetase-1 (mPGES-1) is an inducible terminal enzyme that produces prostaglandin E₂ (PGE₂). In our previous study, we investigated the role of mPGES-1 in the inflammation and demyelination observed in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, using mPGES - 1 -deficient ( mPGES-1 -/- ) and wild-type (wt) mice. We found that mPGES-1 facilitated inflammation, demyelination, and paralysis and was induced in vascular endothelial cells and macrophages and microglia around inflammatory foci. Here, we investigated the role of interleukin-1β (IL-1β) in the intercellular mechanism stimulated by mPGES-1 in EAE spinal cords in the presence of inflammation. We found that the area invaded by CD4-positive (CD4⁺) T cells was extensive, and that PGE₂ receptors EP1-4 were more induced in activated CD4⁺ T cells of wt mice than in those of mPGES - 1 -/- mice. Moreover, IL-1β and IL-1 receptor 1 (IL-1r1) were produced by 65% and 48% of CD4⁺ T cells in wt mice and by 44% and 27% of CD4⁺ T cells in mPGES-1 -/- mice. Furthermore, interleukin-17 (IL-17) was released from the activated CD4⁺ T cells. Therefore, mPGES-1 stimulates an intercellular interaction between CD4⁺ T cells by upregulating the autocrine function of IL-1β in activated CD4⁺ T cells, which release IL-17 to facilitate axonal and myelin damage in EAE mice.

Effects of ultraviolet irradiation on prostaglandin-E2 production by cultured corneal stromal cells

International Nuclear Information System (INIS)

Weinreb, R.N.; Yue, B.Y.J.T.; Peyman, G.A.

1990-01-01

The authors examined the effects of ultraviolet (UV) irradiation on the release of prostaglandin E 2 (PGE 2 ) by rabbit corneal stromal cells in culture. Considerable amounts of PGE 2 were present in the media of control corneal cultures following 1, 2, 4, 8 and 24 hr of incubation. Irradiation with UV-A (320-400 nm) for 30 min resulted in more than a 50% increase in PGE 2 release. Dexamethasone inhibited PGE 2 release by corneal stromal cells. It was, however, ineffective in protecting the cells from the UV-induced release of PGE 2 . (author)

17 bit 4.35 mW 1 kHz Delta Sigma ADC and 256-to-1 multiplexer for remote handling instrumentation equipment

Energy Technology Data Exchange (ETDEWEB)

Verbeeck, Jens, E-mail: jens.verbeeck@esat.kuleuven.be [KU Leuven, Department ESAT-MICAS, Kasteelpark Arenberg 10, 3001 Heverlee (Belgium); KH Kempen University College, IBW-RELIC, Kleinhoefstraat 4, 2440 Geel (Belgium); Van Uffelen, Marco [Fusion for Energy, c/Josep, n° 2, Torres Diagonal Litoral, Ed. B3, 08019 Barcelona (Spain); Steyaert, Michiel [KU Leuven, Department ESAT-MICAS, Kasteelpark Arenberg 10, 3001 Heverlee (Belgium); Leroux, Paul [KU Leuven, Department ESAT-MICAS, Kasteelpark Arenberg 10, 3001 Heverlee (Belgium); KH Kempen University College, IBW-RELIC, Kleinhoefstraat 4, 2440 Geel (Belgium)

2013-10-15

Highlights: ► We present a radiation hard 17 bit-1 kHz 4.35 mW Delta Sigma ADC. ► A radiation tolerant 256-to-1 multiplexer is shown. ► We propose a generic radiation tolerant ASIC for use in an instrumentation link. ► The ASIC can interface more than hundred pressure or resistive sensors. ► All building blocks have a simulated radiation tolerance of more than 1 MGy. -- Abstract: A radiation tolerant Delta-Sigma Analog-to-Digital Converter (ADC) and multiplexer is presented. The design features a 1.5 V, 17 bit ADC consuming 4.35 mW at a sample frequency of 1 MHz. The ADC features a bandwidth of 1 kHz and utilizes a Correlated Double Sampling technique (CDS) to remove offset and 1/f noise. The circuit maintains its 17 bit resolution upon a simulated radiation dose exceeding 1 MGy and varying temperatures between 0 °C and 85 °C. Next a multiplexer is presented. It can multiplex 256 channels at a clock frequency of 128 MHz or has a data throughput of 256 MSample/s. In addition the bit period of the multiplexer varies less then 1.5% due to the influence of temperature or radiation, which proves the temperature and radiation tolerance.

Interleukin 1α inhibits prostaglandin E2 release to suppress pulsatile release of luteinizing hormone but not follicle-stimulating hormone

International Nuclear Information System (INIS)

Rettori, V.; McCann, S.M.; Gimeno, M.F.; Karara, A.; Gonzalez, M.C.

1991-01-01

Interleukin 1α (IL-1α), a powerful endogenous pyrogen released from monocytes and macrophages by bacterial endotoxin, stimulates corticotropin, prolactin, and somatotropin release and inhibits thyrotropin release by hypothalamic action. The authors injected recombinant human IL-1α into the third cerebral ventricle, to study its effect on the pulsatile release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in conscious, freely moving, ovariectomized rats. Intraventricular injection of 0.25 pmol of IL-1α caused an almost immediate reduction of plasma LH concentration. To determine the mechanism of the suppression of LH release, mediobasal hypothalamic fragments were incubated in vitro with IL-1α (10 pM) and the release of LH-releasing hormone (LHRH) and prostaglandin E 2 into the medium was measured by RIA in the presence or absence of nonrepinephrine. 1α reduced basal LHRH release and blocked LHRH release induced by nonrepinephrine. In conclusion, IL-1α suppresses LH but not FSH release by an almost complete cessation of pulsatile release of LH in the castrated rat. The mechanism of this effect appears to be by inhibition of prostaglandin E 2 -mediated release of LHRH

Decreased production of interleukin-6 and prostaglandin E2 associated with inhibition of delta-5 desaturation of omega6 fatty acids in mice fed safflower oil diets supplemented with sesamol.

Science.gov (United States)

Chavali, S R; Forse, R A

1999-12-01

The differences in the immune responses in mice fed sesame oil diets and those fed sesamin may be attributed to the presence of other lignans in the non-fat portion of the oil. The fatty acid composition (mean +/- SD mol. %) of liver membrane phospholipids and the levels of endotoxin-induced prostaglandin (PG) E2, interleukin (IL)-6, IL-10, IL-12 and tumor necrosis factor (TNF)-alpha were determined in mice fed diets supplemented with 5% safflower oil (SO) in the absence or presence of 1% sesamol. The levels of dihomo-gamma-linolenic acid (20:3omega6) were markedly higher (P<0.025) in the livers from mice fed sesamol supplemented SO diets (1.6 +/- 0.1) compared to the controls (1.4 +/- 0.1). These data suggest that sesamol or its metabolite could inhibit the in vivo delta-5 desaturation of omega6 fatty acids. Further, in animals fed sesamol supplemented SO diets, the levels of PGE2 (228 +/- 41 pg/ml) were markedly lower (P<0.01) compared to those fed SO diet alone (1355 +/- 188 pg/ml). Concomitantly, the concentrations of IL-6 were also lower (P<0.01) in mice fed sesamol diet (63 +/- 11 ng/ml) compared to the controls (143 +/- 22 ng/ml). A marked reduction in the levels of PGE2 in animals fed sesamol diets suggests that sesamol or its metabolite could inhibit the activity of cyclooxygenase enzyme.

Close teamwork between Nrf2 and peroxiredoxins 1 and 6 for the regulation of prostaglandin D2 and E2 production in macrophages in acute inflammation.

Science.gov (United States)

Ishii, Tetsuro

2015-11-01

Inflammation is a complex biological self-defense reaction triggered by tissue damage or infection by pathogens. Acute inflammation is regulated by the time- and cell type-dependent production of cytokines and small signaling molecules including reactive oxygen species and prostaglandins. Recent studies have unveiled the important role of the transcription factor Nrf2 in the regulation of prostaglandin production through transcriptional regulation of peroxiredoxins 1 and 6 (Prx1 and Prx6) and lipocalin-type prostaglandin D synthase (L-PGDS). Prx1 and Prx6 are multifunctional proteins important for cell protection against oxidative stress, but also work together to facilitate production of prostaglandins E2 and D2 (PGE2 and PGD2). Prx1 secreted from cells under mild oxidative stress binds Toll-like receptor 4 and induces NF-κB activation, important for the expression of cyclooxygenase-2 and microsomal PGE synthase-1 (mPGES-1) expression. The activated MAPKs p38 and ERK phosphorylate Prx6, leading to NADPH oxidase-2 activation, which contributes to production of PGD2 by hematopoietic prostaglandin D synthase (H-PGDS). PGD2 and its end product 15-deoxy-∆(12,14)-prostaglandin J2 (15d-PGJ2) activate Nrf2 thereby forming a positive feedback loop for further production of PGD2 by L-PGDS. Maintenance of cellular glutathione levels is an important role of Nrf2 not only for cell protection but also for the synthesis of prostaglandins, as mPGES-1 and H-PGDS require glutathione for their activities. This review is aimed at describing the functions of Prx1 and Prx6 in the regulation of PGD2 and PGE2 production in acute inflammation in macrophages and the importance of 15d-PGJ2 as an intrinsic Nrf2 activator. Copyright © 2015 Elsevier Inc. All rights reserved.

Dual inhibition of nitric oxide and prostaglandin E-2 production by polysubstituted 2-aminopyrimidines

Czech Academy of Sciences Publication Activity Database

Zídek, Z.; Kverka, Miloslav; Dusilová, Adéla; Kmoníčková, E.; Jansa, P.

2016-01-01

Roč. 57, July 1 (2016), s. 48-56 ISSN 1089-8603 Institutional support: RVO:61388971 Keywords : Pyrimidines * Nitric oxide * Prostaglandin E-2 Subject RIV: EE - Microbiology, Virology Impact factor: 4.181, year: 2016

Urinary prostaglandin E and vasopressin excretion in essential fatty acid-deficient rats

DEFF Research Database (Denmark)

Hansen, Harald S.; Jensen, B.

1983-01-01

excretion of prostaglandin E (PGE), immunoreactive arginine vasopressin (iA VP), and kallikrein were determined. PGE was quantitated with a radioimmunoassay having 4.9% cross-reactivity with prostaglandin E (PGE). After 4 weeks on the diet, water consumption and urinary iAVP excretion increased....... Increased water consumption and increased urinary iAVP excretion seem to be early symptoms (after 4 weeks) of EFA deficiency, whereas decreased urine output and decreased urinary PGE excretion occur much later (after 10 weeks). Two energy% linolenate supplementation to a fat-free diet did not change...

Do stress responses promote leukemia progression? An animal study suggesting a role for epinephrine and prostaglandin-E2 through reduced NK activity.

Directory of Open Access Journals (Sweden)

Shelly Inbar

2011-04-01

Full Text Available In leukemia patients, stress and anxiety were suggested to predict poorer prognosis. Oncological patients experience ample physiological and psychological stress, potentially leading to increased secretion of stress factors, including epinephrine, corticosteroids, and prostaglandins. Here we tested whether environmental stress and these stress factors impact survival of leukemia-challenged rats, and studied mediating mechanisms. F344 rats were administered with a miniscule dose of 60 CRNK-16 leukemia cells, and were subjected to intermittent forced swim stress or to administration of physiologically relevant doses of epinephrine, prostaglandin-E(2 or corticosterone. Stress and each stress factor, and/or their combinations, doubled mortality rates when acutely applied simultaneously with, or two or six days after tumor challenge. Acute administration of the β-adrenergic blocker nadolol diminished the effects of environmental stress, without affecting baseline survival rates. Prolonged β-adrenergic blockade or COX inhibition (using etodolac also increased baseline survival rates, possibly by blocking tumor-related or normal levels of catecholamines and prostaglandins. Searching for mediating mechanisms, we found that each of the stress factors transiently suppressed NK activity against CRNK-16 and YAC-1 lines on a per NK basis. In contrast, the direct effects of stress factors on CRNK-16 proliferation, vitality, and VEGF secretion could not explain or even contradicted the in vivo survival findings. Overall, it seems that environmental stress, epinephrine, and prostaglandins promote leukemia progression in rats, potentially through suppressing cell mediated immunity. Thus, patients with hematological malignancies, which often exhibit diminished NK activity, may benefit from extended β-blockade and COX inhibition.

Gingival inflammation assessed by histology, 3H-estrone metabolism and prostaglandin E2 levels

International Nuclear Information System (INIS)

Holmes, L.G.; ElAttar, T.M.A.

1977-01-01

Gingival samples were histologically evaluated and placed in two groups, 7 samples each. Group 1 was normal gingiva with no or very few inflammatory cells and group 2 was inflamed gingiva with moderately dense accumulation of imflammatory cells in isolated areas, and sparse distribution in other areas. One hundred to three hundred mg gingival tissue samples were separately homogenized in 7 ml of 0.1 M potasssium phosphate buffer (pH 7.4) and incubated with 1.51 x 10 -4 μM of 3 H-estrone in the presence of NADPH at 37 deg for three hours. Organic solvent extracts of the homogenates were separated by silica gel thin layer chromatography and the radioactivity incorporated in estrone (E 1 ) and estradiol-17 β (E 2 ) zones was extracted with methanol and measured by liquid scintillation spectrometry. The rate conversion of (E 1 ) to (E 2 ) in normal and inflamed gingiva was 4.4 and 8.3 x 10 -7 μM/g/min respectively. Prostaglandin E 2 in 3 normal and 2 inflamed gingival samples were 37.8 and 448.7 pmole/g respectively. The significant increase in the biosynthesis of (E 2 ) and PGE 2 in inflamed as compared with normal gingiva could be a systemic factor in aggravating gingival inflammation due to the hyperemic effects of these hormones. (author)

Inhibition of Nitric Oxide and Prostaglandin E 2 Expression by ...

African Journals Online (AJOL)

Inhibition of Nitric Oxide and Prostaglandin E 2 Expression by Methanol Extract of Polyopes affinis in Lipopolysaccharide-stimulated BV2 Microglial Cells through Suppression of Akt-dependent NF-kB Activity and MAPK Pathway.

Prostaglandin E1 in conjunction with high doses of vitamin B12 improves nerve conduction velocity of patients with diabetic peripheral neuropathy

Institute of Scientific and Technical Information of China (English)

Jilai Li; Zhirong Wan

2008-01-01

BACKGROUND: Prostaglandin E1 improves diabetic peripheral neuropathy in symptoms and sensory threshold. Vitamin B1 and methyl-vitamin B12 improve microcirculation to peripheral nerve tissue and promote neurotrophy.OBJECTIVE: To observe motor nerve and sensory nerve conduction velocity in patients with diabetic peripheral neuropathy, prior to and after treatment with prostaglandin E1, vitamin B1 and different doses of vitamin B12.DESIGN, TIME AND SETTING: Randomized, controlled experiment, performed at the Department of Neurology. Beijing Hantian Central Hospital, between February 2002 and September 2007.PARTICIPANTS: A total of 122 patients with type 2 diabetic peripheral neuropathy; 73 males and 49 females were included. All patients met the diagnostic criteria of diabetes mellitus, as determined by the World Health Organization in 1999 and 2006, and also the diagnostic criteria of diabetic peripheral neuropathy. For each subject, conduction disorders in the median nerve and in the common peroneal nerve were observed using electromyogram. Also, after diet and drug treatment, the blood glucose level of subjects was observed to be at a satisfactory level for more than two weeks, and the symptoms of diabetic peripheral neuropathy were not alleviated.METHODS: All patients were randomly divided into the following three groups. A control group (n=40), in which, 100mg vitamin B1 and 500μg vitamin B12 were intramuscularly injected. A vitamin B12 low-dose treated group (n=42), in which 10μg prostaglandin E1 in 250mL physiological saline was intravenously injected once a day and 100mg vitamin B1 and 500μg vitamin B12 was intramuscularly injected once a day. Lastly, a vitamin B12 high-dose treated group (n=40), in which administration was the same as in the vitamin B12 low-dose treated group, except that 500μg vitamin B12 was replaced by 1mg vitamin B12. Administration was performed for four weeks for each group.MAIN OUTCOME MEASURES: The motor nerve and sensory nerve

Comparative study of labour induced by oral prostaglandin E2 and intravenous syntocinon.

Science.gov (United States)

Murray, C P; Clinch, J

1975-03-22

The use of prostaglandin E2 for the induction of labor with intact membranes is described and its effectiveness is compared to intravenous syntocinon. 40 primigravida and 60 multigravid patients with previous medical and obstetrical histories were studied. The patients were numbered as they entered the trial, with the odd numbers in each group being given oral prostaglandin and the even numbers intravenous syntocinon. In no case was the pregnancy less than 38 weeks maturity. No patient was in labor prior to being given either drug. Prostaglandin E2 (PGE2) was supplied in ampoules containing 5 milligrams in 0.5 milliliter of ethanol. This was added to 49.5 milliliters of sterile water to produce a concentration of the drug of 0.1 milligrams per ml. The syntocinon infusion was prepared by putting 20 units of syntocinon into 1 liter of 5% dextrose in water to produce a solution concentration of 20 mu/ml. The accepted criteria for diagnosing established labor for both groups of patients was the presence of uterine contractions occurring once every 3 minutes, associated with progressive dilatation of the cervix. For both groups of patients it was decided that cervical dilatation should be at least 6 cm within 18 hours of the infusion starting. Using this criterion there was only 1 failure, occurring in the 1st primigravid patient given PGE2, the labor in this instance being completed with intravenous syntocinon. A further 8 patients failed to complete the trial as they had to be delivered by cesarian section. Syntocin was considerably more efficient than PGE2 in inducing labor in the remaining 91 patients particularly in primigravida. This was the case whether judged by the length of labor or by the induction delivery interval. Toco-dynamometric studies showed that the contractions produced by prostaglandin more closely resembled those of normal labor and were less painful.

A new identification method for energetic ion {delta}E-E telescopes

Energy Technology Data Exchange (ETDEWEB)

Martin, Cesar [Departamento de Fisica, Universidad de Alcala, 28871 Alcala de Henares, Madrid (Spain); Institut fuer Experimentelle und Angewandte Physik, Christian-Albrechts, Universitaet zu Kiel, 24118 Kiel (Germany); Bronchalo, Enrique [Departamento de Fisica, Universidad de Alcala, 28871 Alcala de Henares, Madrid (Spain); Departamento de Fisica y Arquitectura de Computadores, Universidad Miguel Hernandez, Avda. Universidad s/n, 03202 Elche, Alicante (Spain)], E-mail: ebronchalo@umh.es; Medina, Jose [Departamento de Fisica, Universidad de Alcala, 28871 Alcala de Henares, Madrid (Spain)

2007-11-21

A new ion identification method for {delta}E-E telescopes is presented. The method works by counting data points under {delta}E(E) curves on {delta}E-E diagrams. These curves are obtained by simulating the telescope response to a flux of energetic ions. The method is checked against three published methods applied to several experimental data sets.

Inhibition by AA861 of prostaglandin E2 production by activated peritoneal macrophages of rat

Energy Technology Data Exchange (ETDEWEB)

Ohuchi, K; Watanabe, M; Taniguchi, J; Tsurufuji, S; Levine, L

1983-10-01

Prostaglandin E2 production by rat peritoneal activated macrophages was inhibited by AA861 which had been reported as a selective inhibitor of 5-lipoxygenase from guinea pig peritoneal leukocytes. At a dose of 3.06 microM, prostaglandin E2 production was decreased to 27% of control. No inhibition of the release of (3H)arachidonic acid from the prelabeled macrophages was observed at the dose.

Identification and characterization of a putative human platelet thromboxane A2/prostaglandin H2 receptor

International Nuclear Information System (INIS)

Saussy, D.L. Jr.

1986-01-01

The thromboxane A 2 (TXA 2 ) analog, 9,11-dimethylmethano-11,12-methano-16-(3-iodo-4-hydroxyphenyl)-13,14-dihydro-13-aza-15αβ-omega-tetranor TXA 2 (I-PTA-OH) was characterized as a competitive antagonist of TXA 2 mimetic-induced platelet aggregation, with a K/sub d/ of 190 nM in platelet rich plasma. This antagonism was specific for the putative thromboxane A 2 /prostaglandin H 2 (TXA 2 /PGH 2 ) receptor, since I-PTA-OH had no inhibitory effects on platelet aggregation stimulated by agonists which act independently of TXA 2 /PGH 2 , and did not inhibit platelet TXA 2 synthesis. [ 125 I]-PTA-OH binding to a particulate fraction from human platelets was saturable, displaceable, and linear with protein concentration. Scatchard analysis of equilibrium binding revealed a single class of high affinity binding sites, with a K/sub d/ of 30 +/- 4 nM and a B/sub max/ of 1.8 +/- 0.3 pmol/mg protein. Kinetic analysis yielded a k 1 of 1.35 x 10 6 M -1 x min -1 and a k√ 1 of 0.032 min -1 , K/sub d/ = k√ 1 /k 1 = 24 nM. The subcellular localization of the putative TXA 2 /PGH 2 receptor was determined using [ 125 I]-PTA-OH binding as a marker for the receptor. [ 125 I]-PTA-OH binding as a marker for the receptor. [ 125 I]-PTA-OH binding, was coenriched with markers for plasma membranes and dense tubular system; but not with markers for cytoplasmic constituents, mitochondria, or granules

Enzymatic synthesis of tritium-labelled prostaglandin D[sub 2] and its conversion to other prostaglandins

Energy Technology Data Exchange (ETDEWEB)

Shram, S.I.; Lazurkina, T.Yu.; Shevchenko, V.P.; Nagaev, I.Yu.; Myasoedov, N.F. (AN SSSR, Moscow (Russian Federation). Inst. Molekulyarnoj Genetiki)

1994-04-01

The one-stage enzymatic synthesis of tritium-labelled prostaglandin D[sub 2] from labelled arachidonic acid was performed by using the enzyme system PGH-synthetase/PGH-PGD-isomerase. By enzymatic and chemical transformation of [[sup 3]H]PGD[sub 2] the following compounds were obtained: 15-keto-13,14-dihydro-[[sup 3]H]PGD[sub 2], 9[alpha],11[beta]-[[sup 3]H]PGF[sub 2], 9-deoxy-[Delta][sup 9]-[[sup 3]H]-PGD[sub 2] ([[sup 3]H]PGJ[sub 2]) and [Delta][sup 12]-13,14-dihydro-[[sup 3]H]PGJ[sub 2]. It was found that L-selectride is a more effective reducing agent than sodium borohydride in the synthesis of 9[alpha], 11[beta]-[[sup 3]H]PGF[sub 2]. (Author).

Characterization of biosynthesis and modes of action of prostaglandin E2 and prostacyclin in guinea pig mesenteric lymphatic vessels.

Science.gov (United States)

Rehal, Sonia; Blanckaert, Pauline; Roizes, Simon; von der Weid, Pierre-Yves

2009-12-01

Rhythmical transient constrictions of the lymphatic vessels provide the means for efficient lymph drainage and interstitial tissue fluid balance. This activity is critical during inflammation, to avoid or limit oedema resulting from increased vascular permeability, mediated by the release of various inflammatory mediators. In this study, we investigated the mechanisms by which prostaglandin E(2) (PGE(2)) and prostacyclin modulate lymphatic contractility in isolated guinea pig mesenteric lymphatic vessels. Quantitative RT-PCR was used to assess the expression of mRNA for enzymes and receptors involved in the production and action of PGE(2) and prostacyclin in mesenteric collecting lymphatic vessels. Frequency and amplitude of lymphatic vessel constriction were measured in the presence of these prostaglandins and the role of their respective EP and IP receptors assessed. Prostaglandin E(2) and prostacyclin decreased concentration-dependently the frequency, without affecting the amplitude, of lymphatic constriction. Data obtained in the presence of the EP(4) receptor antagonists, GW627368x (1 microM) and AH23848B (30 microM) and the IP receptor antagonist CAY10441 (0.1 microM) suggest that PGE(2) predominantly activates EP(4), whereas prostacyclin mainly stimulates IP receptors. Inhibition of responses to either prostaglandin with H89 (10 microM) or glibenclamide (1 microM) suggested a role for the activation of protein kinase A and ATP-sensitive K(+) channels. Our findings characterized the inhibition of lymphatic pumping induced by PGE(2) or prostacyclin in guinea pig mesenteric lymphatics. This action is likely to impair oedema resolution and to contribute to the pro-inflammatory actions of these prostaglandins.

Bone changes from prostaglandin therapy

International Nuclear Information System (INIS)

Poznanski, A.K.; Fernbach, S.K.; Berry, T.E.; Northwestern Univ., Chicago, IL

1985-01-01

Prostaglandin E therapy in infants causes periosteal elevation. Although the changes usually take 30-40 days to become visible, we have seen them as early as nine days. In 15 infants who had prostaglandin E therapy for over six days, three developed periosteal elevation. Three other cases are described in greater detail, with long-term follow-up in two in which the bone remodeled to normal. Gallium scan in one showed increased uptake in areas involved. The periosteal cloaking may mimic Caffey disease but the pattern of involvement is different, since the mandible, which is commonly affected in Caffey disease, is rarely involved in prostaglandin E therapy. (orig.)

Altered aortic and cremaster muscle prostaglandin synthesis in diabetic rats

International Nuclear Information System (INIS)

Myers, T.O.; Messina, E.J.; Rodrigues, A.M.; Gerritsen, M.E.

1985-01-01

Alterations in the synthesis and release of prostaglandins have been reported in humans and animal models of diabetes mellitus. In the present study synthesis and release of prostaglandins by thoracic aorta and cremaster muscle of rats with streptozotocin-induced diabetes of 8 wk duration was compared with age-matched controls. Prostaglandin synthesis was assessed by the measurement of immunoreactive prostaglandin E2 (PGE2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) release and by quantifying metabolism of exogenous [1- 14 C]arachidonic acid by thoracic aortic rings and minced cremaster muscle. These studies indicate that diminished prostacyclin (PGI2) and/or PGE2 production is not a general feature of all diabetic vascular tissues, suggesting that large and small blood vessels may not be similarly affected by diabetes in regard to the metabolism of exogenous arachidonic acid and the synthesis and release of prostaglandins. Furthermore, the vascular changes often observed in conjunction with diabetes, i.e., alterations in vascular reactivity and microangiopathy in small blood vessels and atherosclerosis of large blood vessels may be related in some way to the segmental differences observed in prostaglandin synthesis

Muscarinic M1 receptor inhibition reduces gastroduodenal bicarbonate secretion and promotes gastric prostaglandin E2 synthesis in healthy volunteers

DEFF Research Database (Denmark)

Mertz-Nielsen, A; Hillingsø, Jens; Eskerod, O

1995-01-01

stimulated gastric and basal duodenal bicarbonate secretion by about 50% (p basal and vagally stimulated PGE2 output increased significantly (p ...The selective muscarinic M1 receptor antagonist, pirenzepine, considerably stimulates duodenal mucosal bicarbonate secretion in the rat and increases gastric luminal release of prostaglandin E2 (PGE2) in humans. This study, therefore, looked at the effect of pirenzepine on bicarbonate secretion...... sham feeding and acid exposure (HCl 0.1 M; 20 ml; 5 min) of the duodenal bulb increased mucosal bicarbonate secretion from 191 (14) mumol/cm x h to 266 (27) mumol/cm x h (p basal and vagally...

A positive feedback loop between progesterone and microsomal prostaglandin E synthase-1-mediated PGE2 promotes production of both in mouse granulosa cells.

Science.gov (United States)

Tamura, Kazuhiro; Naraba, Hiroaki; Hara, Takahiko; Nakamura, Kota; Yoshie, Mikihiro; Kogo, Hiroshi; Tachikawa, Eiichi

2016-03-01

Microsomal prostaglandin E synthase-1 (mPGES-1) is primarily expressed in granulosa cells (GCs) in the preovulatory follicle. Both prostaglandin E2 (PGE2) and progesterone (P4) are implicated in various reproductive functions. Here, we demonstrate that mPges-1 may be a direct downstream target gene of the P4 receptor and P4-stimulated PGE2 secretion can stimulate P4 production in a newly generated mouse GC line (GtsT). Treatment of GtsT cells with a P4 receptor agonist, norgestrel, markedly increased mPGES-1 expression detected by RT-PCR analysis. PGE2 secretion measured by an enzyme-linked immunosorbent assay was enhanced by P4 treatment. Luciferase assays revealed that the proximal promoter region of the mPges-1 gene was responsible for the effects of P4 treatment. Conversely, PGE2 treatment stimulated P4 secretion, which coordinated with mRNA expression of steroidogenic acute regulatory protein. Taken together, P4 may regulate mPGES-1 expression to increase PGE2 secretion and in turn P4 production. An autocrine loop between P4 and PGE2 might function to maintain the increased levels of both in GCs. Copyright © 2016 Elsevier Inc. All rights reserved.

Effective Lagrangians, Watson's theorem and the E2/M1 mixing ratio in the excitation of the Delta resonance

International Nuclear Information System (INIS)

Davidson, R.M.

1992-01-01

The author investigates theoretical uncertainties and model dependence in the extraction of the nucleon-delta(1232) electromagnetic transition amplitudes from the multipole data base. The starting point is an effective Lagrangian incorporating chiral symmetry, which includes at the tree level the pseudovector Born terms, leading t-channel vector meson exchanges, and s and u channel delta exchanges. The nucleon-delta magnetic dipole (M1) and electric quadrupole (E2) transition amplitudes are expressed in terms of two independent gauge couplings at the γNΔ vertex. After unitarizing the tree level amplitude, the gauge couplings are fitted to various multipole data sets, thus determining E2 and M1. Although there is much sensitivity to the method used to unitarize the amplitude, the author extracts the E2/M1 ratio to be negative, with a magnitude around 1.5%. 11 refs., 3 figs

Effects of treatments for experimental bone tumor on prostaglandin E level and bone scintigrams

Energy Technology Data Exchange (ETDEWEB)

Otsuka, Nobuaki; Ito, Yasuhiko; Yoneda, Masaya; Muranaka, Akira; Nishishita, Soichi; Morita, Rikushi [Kawasaki Medical School, Kurashiki, Okayama (Japan)

1983-10-01

The role of Prostaglandin E (PgE) level was studied experimentally as follows: 1) intrahepatic implantation of VX-2, 2) intravenous injection of VX-2, 3) effect of treatments on intramedullary implanted VX-2. The levels of PgE in intrahepatic and intravenous transplantation were not higher than that of intramedullary transplantation. Mitomycin C (MMC) did not reduce the PgE level and appearance time of bone scan abnormality was the same as that of untreated animals. A combination of indomethacin and MMC caused a delay in appearance time of bone scan abnormalities.

Impact of FDA-Approved Drugs on the Prostaglandin Transporter OATP2A1/SLCO2A1.

Science.gov (United States)

Kamo, Shunsuke; Nakanishi, Takeo; Aotani, Rika; Nakamura, Yoshinobu; Gose, Tomoka; Tamai, Ikumi

2017-09-01

To understand interaction of drugs with the prostaglandin transporter OATP2A1/SLCO2A1 that regulates disposition of prostaglandins, we explored the impact of 636 drugs in an FDA-approved drug library on 6-carboxyfluorescein (6-CF) uptake by OATP2A1-expressing HEK293 cells (HEK/2A1). Fifty-one and 10 drugs were found to inhibit and enhance 6-CF uptake by more than 50%, respectively. Effect of the 51 drugs on 6-CF uptake was positively correlated with that on PGE 2 uptake (r = 0.64, p < 0.001). Among those, 5 drugs not structurally related to prostaglandins, suramin, pranlukast, zafirlukast, olmesartan medoxomil, and losartan potassium, exhibited more than 90% PGE 2 uptake inhibition. Inhibitory affinity of suramin to OATP2A1 was the highest (IC 50,2A1 of 0.17 μM), and its IC 50 values to MRP4-mediated PGE 2 transport (IC 50,MRP4 ) and PGE 2 synthesis in human U-937 cells treated with phorbol 12-myristate 13-acetate (IC 50,Syn ) were 73.6 and 336.7 times higher than IC 50,2A1 , respectively. Moreover, structure-activity relationship study in 29 nonsteroidal anti-inflammatory drugs contained in the library displayed inhibitory activities of anthranilic acid derivatives, but enhancing effects of propionic acid derivatives. These results demonstrate that suramin is a potent selective inhibitor of OATP2A1, providing a comprehensive information about drugs in clinical use that interact with OATP2A1. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Long-term efficacy and safety of self-intracavernous injection of prostaglandin E1 for treatment of erectile dysfunction in China.

Science.gov (United States)

He, L; Wen, J; Jiang, X; Chen, H; Tang, Y

2011-06-01

The study evaluated the long-term efficacy and safety profiles of self-intracavernous injection of prostaglandin E1 (PGE1) for erectile dysfunction (ED). Four hundred and sixteen ED patients were treated with self-intracavernous injection of PGE1 from January 1998 to December 2007 in our outpatient service. Follow-up was made to investigate the efficacy and side effects of this treatment. It was found that 261 patients (62.7%) felt satisfied and kept using this treatment due to its advantages of satisfactory efficacy and reasonable expense. Twenty-seven of them (6.5%) got rid of PGE1 treatment after five times injections and did not need any other drugs to maintain satisfactory sexual lives. Two hundred and fourteen (51.4%) patients kept using this treatment for over 1 year, 26 (6.2%) over 5 years, 12 (2.9%) over 8 years and 7 (1.7%) over 10 years. The major complications of self-intracavernous injection of PGE1 include fibrosis of corpus cavernosum (three cases), ecchymosis associated with vascular injury due to injection (23 cases) and pain associated with injection (295 cases). There were no patients displaying priapism. It is concluded that self-intracavernous injection of PGE1 is a safe and effective treatment for ED with various aetiologies and a broad range of severity, and no serious complications were observed after long-term application. © 2011 Blackwell Verlag GmbH.

In vitro effect of. Delta. sup 9 -tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E sub 2

Energy Technology Data Exchange (ETDEWEB)

Rettori, V.; Aguila, M.C.; McCann, S.M. (Univ. of Texas Southwestern Medical Center at Dallas (United States)); Gimeno, M.F.; Franchi, A.M. (Centro de Estudios Farmacologicos y de Principios Naturales, Buenos Aires (Argentina))

1990-12-01

Previous in vivo studies have shown that {Delta}{sup 9}-tetrahydrocannabinol (THC), the principal active ingredient in marijuana, can suppress both luteinizing hormone (LH) and growth hormone (GH) secretion after its injection into the third ventricle of conscious male rats. The present studies were deigned to determine the mechanism of these effects. Various doses of THC were incubated with either stalk median eminence fragments (MEs) or mediobasal hypothalamic (MBH) fragments in vitro. Although THC (10 nM) did not alter basal release of LH-releasing hormone (LHRH) from MEs in vitro, it completely blocked the stimulatory action of dopamine or nonrepinephrine on LHRH release. The effective doses to block LHRH release were associated with a blockade of synthesis and release of prostaglandin E{sub 2} (PGE{sub 2}) from MBH in vitro. In contrast to the suppressive effect of THC on LHRH release, somatostatin release from MEs was enhanced in a dose-related manner with a minimal effective dose of 1 nM. Since PGE{sub 2} suppresses somatostatin release, this enhancement may also be related to the suppressive effect of THC on PGE{sub 2} synthesis and release. The authors speculate that these actions are mediated by the recently discovered THC receptors in the tissue. The results indicate that the suppressive effect of THC on LH release is mediated by a blockade of LHRH release, whereas the suppressive effect of the compound on growth hormone release is mediated, at least in part, by a stimulation of somatostatin release.

Effect of Intravasclar Influsion of Endogenous Pyrogen or Prostaglandin E2 on Neuronal Activity of Rat's Hypothalamus

OpenAIRE

Sakata, Yoshiyuki; Watanabe, Tatsuo; Morimoto, Akio; Murakami, Naotoshi

1989-01-01

We investigated the effects of intracarotid infusion of prostaglandin E2 or intravenous infusion of an endogenous pyrogen on the neuronal activity of the neuronal activity of the preoptic and anterior hypothalamic (PO/AH) region in rats. The present results suggest that thermore sponsive neurons of the PO/AH region respond well to intravascular application of prostaglandin E2 or the endogenous pyrogen, compared with thermally insensive neurons. Intravenous infusion of the endogenous pyrogen a...

Utilization of dE/dx approx E sup n /a dependence for DELTA E - E-spectrometer calibration

CERN Document Server

Gorpinich, O K; Jachmenov, O O

2002-01-01

The method of calibration of DELTA E - E-spectrometers by the use of known empiric form dE/dx approx E sup n /a which describes the specific energy loss of charge particles in the matter for energy calibration of DELTA E - E-spectrometer was designed.

A role of prostaglandin E/sub2/ in radiation-induced hyperthermia

International Nuclear Information System (INIS)

Cernak, I.; Stanimirovic, D.; Simovic, M.; Ivanovic, L.; Markovic, M.; Savic, J.

1989-01-01

Radiation-induced (6.7 Gy X-ray) changes in body temperature were investigated in rats exposed to: whole body irradiation pretreatment with indomethacin (5 mg/kg b.w.) 30 min before whole body irradiation and irradiation of the body with protected head. Content of prostaglandin E 2 (PGE 3 ) was measured in the rat brain hypothalamic regions and compared to correspondent body temperature. Hypothalamic PGE 2 content strongly correlated with body temperature (r=0.79, p 2 in the hypothalamus is presumed as a putative mediator of radiation-induced changes in body temperature. (author). 8 refs.; 2 figs.; 1 tab

Prostaglandin levels and lysosomal enzyme activities in irradiated rats

International Nuclear Information System (INIS)

Trocha, P.J.; Catravas, G.N.

1980-01-01

Whole-body irradiation of rats results in the release of hydrolases from lysosomes, an increase in lysosomal enzyme activities, and changes in the prostaglandin levels in spleen and liver tissues. A transient increase in the concentration of prostaglandins E and F and leakage of lysosomal hydrolases occurred in both spleen and liver tissues 3-6 hours after the animals were irradiated. Maximal values for hydrolase activities, prostaglandin E and F content, and release of lysosomal enzymes were found 4 days postirradiation in rat spleens whereas in the liver only slight increases were observed at this time period for prostaglandin F levels. On day 7 there was a final rise in the spleen's prostaglandin E and F concentrations and leakage of hydrolases from the lysosomes before returning to near normal values on day 11. The prostaglandin F concentration in liver was also slightly elevated on the 7th day after irradiation and then decreased to control levels. (author)

9-Hydroxyprostaglandin dehydrogenase activity in the adult rat kidney. Regional distribution and sub-fractionation.

Science.gov (United States)

Asciak, C P; Domazet, Z

1975-02-20

1. Catabolism of prostaglandin F2alpha in the adult rat kidney takes place by the following sequence of enzymatic steps: (1) 15-hydroxyprostaglandin dehydrogenase; (2) prostaglandin delta13-reductase; and (3) 9-hydroxyprostaglandin dehydrogenase. 2. 9-Hydroxyprostaglandin dehydrogenase activity was highest in the cortex with lesser amounts in the medulla and negligible activity detected in the papilla. A similar distribution was observed for 15-hydroxyprostaglandin dehydrogenase and prostaglandin delta13-reductase. 3. Most of the 9-hydroxyprostaglandin dehydrogenase activity in the homogenate was found in the high-speed supernatant as also observed for 15-hydroxyprostaglandin dehydrogenase and prostaglandin delta13-reductase. 4. These observations indicate that the rat kidney contains an abundance of prostaglandin-catabolising enzymes which favour formation of metabolites of the E-type.

FOXC1 Regulates Expression of Prostaglandin Receptors Leading to an Attenuated Response to Latanoprost.

Science.gov (United States)

Doucette, Lance P; Footz, Tim; Walter, Michael A

2018-05-01

This study examines the effect of FOXC1 on the prostaglandin pathway in order to explore FOXC1's role in the prostaglandin-resistant glaucoma phenotype commonly seen in Axenfeld-Rieger syndrome. Binding and transcriptional activity of FOXC1 to the gene coding for the EP3 prostaglandin receptor (PTGER3) were evaluated through ChIP-qPCR and luciferase-based assays. Immortalized trabecular meshwork cells (TM1) and HeLa cells had FOXC1 mRNA reduced via siRNA interference. qPCR and Western blot experiments were conducted to examine the changes in prostaglandin receptor expression brought about by lowered FOXC1. TM1 cells were then treated with 10 μM latanoprost acid and/or an siRNA for FOXC1. The expression of fibronectin and matrix metalloproteinase 9 were evaluated via qPCR in each treatment condition. ChIP-qPCR and luciferase experiments confirmed that FOXC1 binds to and activates transcription of the EP3 gene prostaglandin receptor. qPCR and Western experiments in HeLa and TM1 cells showed that FOXC1 siRNA knockdown results in significantly lowered EP3 levels (protein and RNA). In addition, RNA levels of the other prostaglandin receptor genes EP1 (PTGER1), EP2 (PTGER2), EP4 (PTGER4), and FP (PTGFR) were altered when FOXC1 was knocked down in TM1 and HeLa cells. Analysis of fibronectin expression in TM1 cells after treatment with 10 μM latanoprost acid showed a statistically significant increase in expression; this increase was abrogated by cotreatment with a siRNA for FOXC1. We show the abrogation of latanoprost signalling when FOXC1 is knocked down via siRNA in a trabecular meshwork cell line. We propose that the lower levels of active FOXC1 in Axenfeld-Rieger syndrome patients with glaucoma account for the lack of response to prostaglandin-based medications.

Fast and simple online sample preparation coupled with capillary LC-MS/MS for determination of prostaglandins in cell culture supernatants

DEFF Research Database (Denmark)

Rinne, Sandra; Ramstad Kleiveland, Charlotte; Kassem, Moustapha

2007-01-01

An online 2-D strong cation exchange (SCX)-RP capillary liquid chromatographic (cLC) method with IT mass spectrometric (IT-MS/MS) detection for the simultaneous determination of prostaglandin (PG) A(1), PGD(2), PGE(1), PGE(2), PGF(2a), 6-keto-(6k)PGF(1a), and 15-Delta(12,14)-deoxy-PGJ(2) (15dPGJ(2...

Efficiency, safety, and patient preference of switching from dorzolamide 1%/timolol 0.5% to brinzolamide 1%/timolol 0.5% while maintaining the prostaglandin F2α analog

Directory of Open Access Journals (Sweden)

Shimizu Y

2015-03-01

Full Text Available Yoshie Shimizu,1 Shunsuke Nakakura,1 Makiko Nishiyama,1 Hitoshi Tabuchi,1 Yoshiaki Kiuchi2 1Department of Ophthalmology, Saneikai Tsukazaki Hospital, Himeji, 2Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan Background: We investigated the efficiency, safety and patient preference of switching from dorzolamide 1%/timolol 0.5% to brinzolamide 1%/timolol 0.5% while maintaining the prostaglandin F2α analog.Methods: We initially enrolled 44 eyes from 44 primary open angle glaucoma patients, and a total of 42 patients completed the study. All patients were under treatment with various prostaglandin F2α analogs and dorzolamide 1%/timolol 0.5%. While maintaining the prostaglandin F2α analog, dorzolamide 1%/timolol 0.5% was switched to brinzolamide 1%/timolol 0.5%. Conjunctival hyperemia, superficial punctate keratopathy, and intraocular pressure (IOP were evaluated at baseline and at 4, 12, and 24 weeks. Adverse events and patient preferences, measured using a questionnaire at study initiation and at 24 weeks, were also noted.Results: The IOP was 17.7±1.7, 16.8±2.6, 16.7±2.2, and 16.7±2.4 mmHg at baseline and at 4, 12, and 24 weeks, respectively, with no significant differences in IOP values at any time point (P=0.117, one-way analysis of variance. In addition, no significant differences were found in the incidence of conjunctival hyperemia or SPK score at any time point (all P>0.5, by Kruskal–Wallis test. Based on the evaluation of side effects using the questionnaire, stinging/burning was less common (P=0.042, while blurred vision was more common (P=0.003, after switching to brinzolamide 1%/timolol 0.5%. Regarding patient preferences, 13 patients (31% preferred dorzolamide 1%/timolol 0.5%, 12 patients (29% preferred brinzolamide 1%/timolol 0.5%, and 17 patients (40% preferred neither.Conclusion: When switching from dorzolamide 1%/timolol 0.5% to brinzolamide 1

Prostaglandins and prostaglandin receptor antagonism in migraine

DEFF Research Database (Denmark)

Antonova, Maria

2013-01-01

Human models of headache may contribute to understanding of prostaglandins' role in migraine pathogenesis. The current thesis investigated the migraine triggering effect of prostaglandin E2 (PGE2) in migraine patients without aura, the efficacy of a novel EP4 receptor antagonist, BGC20....... The infusion of PGE2 caused the immediate migraine-like attacks and vasodilatation of the middle cerebral artery in migraine patients without aura. The highly specific and potent EP4 receptor antagonist, BGC20-1531, was not able to attenuate PGE2-induced headache and vasodilatation of both intra- and extra......-cerebral arteries. The intravenous infusion of PGF2α did not induce headache or statistically significant vasoconstriction of cerebral arteries in healthy volunteers. Novel data on PGE2-provoked immediate migraine-like attacks suggest that PGE2 may be one of the important final products in the pathogenesis...

The Prostaglandin E2-EP3 Receptor Axis Regulates Anaplasma phagocytophilum-Mediated NLRC4 Inflammasome Activation

Czech Academy of Sciences Publication Activity Database

Wang, X.; Shaw, D.K.; Hammond, H.L.; Sutterwala, F.S.; Rayamajhi, M.; Shirey, K.A.; Perkins, D.J.; Bonventre, J.V.; Velayutham, T.S.; Evans, S.M.; Rodino, K.G.; VieBrock, L.; Scanlon, K.M.; Carbonetti, N.H.; Carlyon, J.A.; Miao, E.A.; McBride, J.W.; Kotsyfakis, Michalis; Pedra, J. H. F.

2016-01-01

Roč. 12, č. 8 (2016), č. článku e1005803. E-ISSN 1553-7374 Institutional support: RVO:60077344 Keywords : Rickettsial agents * Anaplasma phagocytophilum * prostaglandin E2-EP3 Receptor Axis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.003, year: 2015

Fabrication of an integrated {Delta}E-E-silicon detector by wafer bonding using cobalt disilicide

Energy Technology Data Exchange (ETDEWEB)

Thungstroem, G. [Mid-Sweden Univ., Sundsvall (Sweden). Dept. of Inf. Technol.]|[Royal Institute of Technology, Department of Electronics, Electrum 229, S-164 40 Kista (Sweden); Veldhuizen, E.J. van [Uppsala University, Department of Radiation Science, Box 535, S-751 21 Uppsala (Sweden); Westerberg, L. [Uppsala University, The Svedberg Laboratory, Box 533, S-751 21 Uppsala (Sweden); Norlin, L.-O. [Royal Institute of Technology, Department of Physics, Frescativaegen 24, S-104 05 Stockholm (Sweden); Petersson, C.S. [Royal Institute of Technology, Department of Electronics, Electrum 229, S-164 40 Kista (Sweden)

1997-06-01

The problem concerning mechanical stability of thin self-supporting {Delta}E detector in a {Delta}E-E semiconductor detector telescope, has been solved by integrating both detectors into one unit. We show here a low-cost method to integrate the detectors by wafer bonding using cobalt disilicide. The {Delta}E-detector has a thickness of 6.5 {mu}m and the E detector 290 {mu}m with an area of 24.8 mm{sup 2}. The system was characterized with secondary ion mass spectroscopy (SIMS), scanning electron microscopy (SEM), electrical measurement, particle measurement and two-dimensional electrical simulation. (orig.).

In vitro prostaglandin E2 stimulation of 45Ca mobilization from chick bone

International Nuclear Information System (INIS)

Satterlee, D.G.; Amborski, G.F.; McIntyre, M.D.; Parker, M.S.; Jacobs-Perry, L.A.

1984-01-01

The ability of prostaglandin E2 (PGE2) to mobilize 45 Ca from chick embryo long bones was assayed in an in vitro bone culture system. Concentrations of PGE2 tested ranged from 10(-9) to 10(-5) M. The PGE2 was effective in stimulating release of 45 Ca from prelabelled bones at all concentrations tested except at 10(-9) M. In addition, stimulation of 45 Ca release could be produced daily for 4 consecutive days of PGE2 culture-pulsing at what appeared to be the optimal PGE2 concentration, 10(-7) M. The authors conclude, as in mammals, PGE2 is a potent stimulator of calcium mobilization from avian bone. The potential involvement of prostaglandins in eggshell formation is discussed

Novel contraceptive targets to inhibit ovulation: the prostaglandin E2 pathway

Science.gov (United States)

Duffy, Diane M.

2015-01-01

BACKGROUND Prostaglandin E2 (PGE2) is an essential intrafollicular regulator of ovulation. In contrast with the one-gene, one-protein concept for synthesis of peptide signaling molecules, production and metabolism of bioactive PGE2 requires controlled expression of many proteins, correct subcellular localization of enzymes, coordinated PGE2 synthesis and metabolism, and prostaglandin transport in and out of cells to facilitate PGE2 action and degradation. Elevated intrafollicular PGE2 is required for successful ovulation, so disruption of PGE2 synthesis, metabolism or transport may yield effective contraceptive strategies. METHODS This review summarizes case reports and studies on ovulation inhibition in women and macaques treated with cyclooxygenase inhibitors published from 1987 to 2014. These findings are discussed in the context of studies describing levels of mRNA, protein, and activity of prostaglandin synthesis and metabolic enzymes as well as prostaglandin transporters in ovarian cells. RESULTS The ovulatory surge of LH regulates the expression of each component of the PGE2 synthesis-metabolism-transport pathway within the ovulatory follicle. Data from primary ovarian cells and cancer cell lines suggest that enzymes and transporters can cooperate to optimize bioactive PGE2 levels. Elevated intrafollicular PGE2 mediates key ovulatory events including cumulus expansion, follicle rupture and oocyte release. Inhibitors of the prostaglandin-endoperoxide synthase 2 (PTGS2) enzyme (also known as cyclooxygenase-2 or COX2) reduce ovulation rates in women. Studies in macaques show that PTGS2 inhibitors can reduce the rates of cumulus expansion, oocyte release, follicle rupture, oocyte nuclear maturation and fertilization. A PTGS2 inhibitor reduced pregnancy rates in breeding macaques when administered to simulate emergency contraception. However, PTGS2 inhibition did not prevent pregnancy in monkeys when administered to simulate monthly contraceptive use. CONCLUSION

Prostaglandin-E2 Mediated Increase in Calcium and Phosphate Excretion in a Mouse Model of Distal Nephron Salt Wasting.

Directory of Open Access Journals (Sweden)

Manoocher Soleimani

Full Text Available Contribution of salt wasting and volume depletion to the pathogenesis of hypercalciuria and hyperphosphaturia is poorly understood. Pendrin/NCC double KO (pendrin/NCC-dKO mice display severe salt wasting under basal conditions and develop profound volume depletion, prerenal renal failure, and metabolic alkalosis and are growth retarded. Microscopic examination of the kidneys of pendrin/NCC-dKO mice revealed the presence of calcium phosphate deposits in the medullary collecting ducts, along with increased urinary calcium and phosphate excretion. Confirmatory studies revealed decreases in the expression levels of sodium phosphate transporter-2 isoforms a and c, increases in the expression of cytochrome p450 family 4a isotypes 12 a and b, as well as prostaglandin E synthase 1, and cyclooxygenases 1 and 2. Pendrin/NCC-dKO animals also had a significant increase in urinary prostaglandin E2 (PGE-2 and renal content of 20-hydroxyeicosatetraenoic acid (20-HETE levels. Pendrin/NCC-dKO animals exhibit reduced expression levels of the sodium/potassium/2chloride co-transporter 2 (NKCC2 in their medullary thick ascending limb. Further assessment of the renal expression of NKCC2 isoforms by quantitative real time PCR (qRT-PCR reveled that compared to WT mice, the expression of NKCC2 isotype F was significantly reduced in pendrin/NCC-dKO mice. Provision of a high salt diet to rectify volume depletion or inhibition of PGE-2 synthesis by indomethacin, but not inhibition of 20-HETE generation by HET0016, significantly improved hypercalciuria and salt wasting in pendrin/NCC dKO mice. Both high salt diet and indomethacin treatment also corrected the alterations in NKCC2 isotype expression in pendrin/NCC-dKO mice. We propose that severe salt wasting and volume depletion, irrespective of the primary originating nephron segment, can secondarily impair the reabsorption of salt and calcium in the thick ascending limb of Henle and/or proximal tubule, and reabsorption of

Difluorothromboxane A2 and stereoisomers: Stable derivatives of thromboxane A2 with differential effects on platelets and blood vessels

International Nuclear Information System (INIS)

Morinelli, T.A.; Okwu, A.K.; Mais, D.E.; Halushka, P.V.; John, V.; Chen, Chienkuang; Fried, J.

1989-01-01

The present study reports on the selective effects on human platelets and canine saphenous veins of four stable difluorinated analogues and thromboxane A 2 (TXA 2 ), in which the characteristic 2,6-dioxa[3.1.1]bicycloheptane structure of TXA 2 has been retained. The four compounds differ in their stereochemistry of the 5,6 double bond and/or the 15-hydroxyl group. Only 10,10-difluoro-TXA 2 (compound I) with the natural stereochemistry of TXA 2 was an agonist in both platelets and canine saphenous veins. (15R)-10,10-Difluoro-TXA 2 (compound II), (5E)-10,10-difluoro-TXA 2 (compound III), and (5E,15R)-10,10-difluoro-TXA 2 (compound IV) were antagonists of platelet aggregation stimulated by compound I. However, compounds II, III, and IV stimulated contraction of canine saphenous veins. All four compounds could displace the TXA 2 /prostaglandin H 2 antagonist 9,11-dimethylmethano-11,12-methano-16-(3- 125 I-4-hydroxyphenyl)-13,14-dihydro-13-aza-15αβ-ω-tetranor-TXA 2 from its platelet receptor. These results support the existence of two subtypes of TXA 2 /prostaglandin H 2 receptors and emphasize the importance of the stereochemical requirements of these TXA 2 analogues for interaction with these receptors. These stable fluorinated TXA 2 analogues should prove useful tools for the further characterization of these and other TXA 2 /prostaglandin H 2 receptors

The I{delta}KI = 1, E1 Transitions in Odd-A isotopes of Tb and Eu

Energy Technology Data Exchange (ETDEWEB)

Malmskog, S G [AB Atomenergi, Nykoeping (Sweden); Marelius, A [Dept. of Physics, Univ. of Uppsala, Uppsala (Sweden); Wahlborn, S [Div. of Theoretical Physics, Royal Inst. of Technology, Stockholm (Sweden); [Research Inst. for Physics, Stockholm (Sweden)

1967-04-15

Life-time measurements have been performed for the 5/2{sup -} [532] intrinsic state in the Tb isotopes with A = 155, 157, 159, and 161. The rates of the {delta}K = 1 E1 transitions in these isotopes, as well as in {sup 153}Eu and {sup 155}Eu, are discussed. With the Nilsson model as a starting point, the effects of pairing correlations and Coriolis coupling are calculated. It is found that these effects are not sufficient to account for the essential features of the experimental results. It is suggested that dipole contributions arising through octupole excitations are of importance.

Prostaglandin E2 facilitates neurite outgrowth in a motor neuron-like cell line, NSC-34

Directory of Open Access Journals (Sweden)

Hiroshi Nango

2017-10-01

Full Text Available Prostaglandin E2 (PGE2 exerts various biological effects by binding to E-prostanoid receptors (EP1-4. Although recent studies have shown that PGE2 induces cell differentiation in some neuronal cells such as mouse DRG neurons and sensory neuron-like ND7/23 cells, it is unclear whether PGE2 plays a role in differentiation of motor neurons. In the present study, we investigated the mechanism of PGE2-induced differentiation of motor neurons using NSC-34, a mouse motor neuron-like cell line. Exposure of undifferentiated NSC-34 cells to PGE2 and butaprost, an EP2-selective agonist, resulted in a reduction of MTT reduction activity without increase the number of propidium iodide-positive cells and in an increase in the number of neurite-bearing cells. Sulprostone, an EP1/3 agonist, also significantly lowered MTT reduction activity by 20%; however, no increase in the number of neurite-bearing cells was observed within the concentration range tested. PGE2-induced neurite outgrowth was attenuated significantly in the presence of PF-0441848, an EP2-selective antagonist. Treatment of these cells with dibutyryl-cAMP increased the number of neurite-bearing cells with no effect on cell proliferation. These results suggest that PGE2 promotes neurite outgrowth and suppresses cell proliferation by activating the EP2 subtype, and that the cAMP-signaling pathway is involved in PGE2-induced differentiation of NSC-34 cells. Keywords: Prostaglandin E2, E-prostanoid receptors, Motor neuron, Neurite outgrowth, cAMP

Simultaneous use of two prostaglandin radioimmunoassays employing two antisera of differing specificity. II. Relative stability of prostaglandins E1, E2, and F1alpha in cell cultures of BALB/c 3T3 and SV3T3 mouse fibroblasts

International Nuclear Information System (INIS)

Ritzi, E.M.; Stylos, W.A.

1976-01-01

The relative stability of Prostaglandins (PGs) E1, E2 and F1α in cultures of BALB/c 3T3 and SV3T3 cells has been evaluated using 3 different approaches. First, total recovery of tritium in the ethyl acetate phase following incubation and extraction of PGF1α and PGE1 demonstrated greater stability for PGF1α (88.8 percent) than PGE1 (65.9 percent). Second, analysis of incubated, extracted, tritiated PGs by thin layer chromatography revealed decreases of up to 23 percent in the PGE zone following incubation of 3H-PGE1. With increasing time of incubation, decreases in the PGE zone were accompanied by increase in PGA-like compounds. 3H-PGF1α demonstrated greater stability, having greater than 90 percent recovery of the tritium in the PGF zone. A third approach to the assessment of PG stability in culture was the comparison of the production of individual PGs by radioimmunoassay (RIA). The data obtained by RIA indicated a lag in the increase of PGA and PGB, until an initial rise in PGE was noted, suggesting that PGA and PGB may be secondary products arising from PGE which exhibits only partial stability in culture. By employing two RIAs, one for total PGE and one for PGA and PGB, the composite determination PG [E + (A + B)] can be used to provide a more meaningful determination of PG production because of the instability of the PGs. On the other hand, individual determinations are helpful in assessing the stability of PGEs in cell cultures

Kinetics of prostaglandin E2 and thromboxane A2 synthesis and suppression of PHA-stimulated peripheral blood mononuclear leucocytes.

Science.gov (United States)

Awara, W; Hillier, K; Jones, D

1986-12-01

The immunomodulatory effects of thromboxane A2 and prostaglandin E2 on peripheral blood mononuclear leucocytes stimulated with PHA in vitro, and the relationship of this to the time-course of their synthesis in culture, were investigated using prostaglandin E2, a thromboxane A2 synthesis inhibitor (UK37248), a thromboxane A2 mimic (U46619) and a thromboxane A2 receptor blocker (EP045). The inhibitory effect of prostaglandin E2 on PHA-induced human peripheral blood mononuclear leucocyte proliferation diminishes if the addition of PGE2 is delayed. If added 4 hr after a maximum concentration of PHA (5 micrograms/ml), the effect of PGE2 was reduced by 60%. If a submaximal concentration of PHA (1 microgram/ml) was used, the effect of PGE2 was not reduced if added 4 hr later but fell by about 60% after 16 hr. UK37248 moderately inhibited PHA-induced activation while substantially inhibiting thromboxane A2 synthesis and simultaneously enhancing PGE2 synthesis. The enhanced accumulation of PGE2 occurs while sensitivity to PGE2 is dropping. U46619, exogenously applied as a thromboxane A2 mimic, inhibited PHA-induced activation at concentrations that did not significantly alter PGE2 synthesis. EP045, which may modulate the effects of endogenous thromboxane A2 by blocking receptors, did not alter PHA-induced activation. We conclude that thromboxane A2 may have a role in inhibiting PHA-induced activation on the basis of the effect of U46619. However, this study highlights difficulties in utilizing prostaglandin and thromboxane receptor and synthesis inhibitors to examine their endogenous role in the modulation of mitogen-induced activation in vitro. If sensitivity to the purported endogenous substance is limited to the early stages of culture and if only low levels are synthesized at this early stage, then blocking drugs would have little effect.

The Value of Intravenous Prostaglandin E2 after Intra-uterine Death

African Journals Online (AJOL)

1974-09-21

Sep 21, 1974 ... ficantly smaller doses of prostaglandins can achieve deli- very of the fetus and an intravenous route will be the method of choice. However, in cases of rhesus iso- immunisation, where larger doses of prostaglandin are required, with correspondingly more severe side-effects, the extra-amniotic route may be ...

Study of 4f hybridization in CeNiX with X=Sn{sub d}eltaGe{sub 1-d}elta, 0<=delta<=1

Energy Technology Data Exchange (ETDEWEB)

Fuente, C. de la, E-mail: cesar@unizar.e [Depto. Fisica de la Materia Condensada, Laboratorio de Magnetismo, Universidad de Zaragoza and ICMA-CSIC (Spain); Moral, A. del [Depto. Fisica de la Materia Condensada, Laboratorio de Magnetismo, Universidad de Zaragoza and ICMA-CSIC (Spain); Adroja, D.T. [ISIS Facility, Rutherford Appleton Laboratory, Chilton, Didcot, Oxfordshire OX11 0QX (United Kingdom); Fraile, A. [Depto. Fisica de la Materia Condensada, Laboratorio de Magnetismo, Universidad de Zaragoza and ICMA-CSIC (Spain); Arnaudas, J.I. [Instituto de Nanociencia de Aragon, Universidad de Zaragoza (Spain)

2010-05-15

We report inelastic neutron scattering and core-level X-ray photoemission spectroscopy experiments for studying the Kondo problem in the CeNiX, X=Sn{sub d}eltaGe{sub 1-d}elta 0<=delta<=1 series. The neutron results confirm that they behave like a Kondo lattice for delta>=0.85, showing broad maxima at around 30 meV, typical of a crystal field magnetic scattering. So, the Ge doping could produce the suppression of the cerium magnetism observed for delta<=0.25. To open a more deep sight on this point, we have analyzed the 3d core-level XPS spectra by using the well-known Gunnarsson-Schoenhammer model. From this analysis, we have obtained the 'on-site' Coulomb bare repulsion for f states, U, and hybridization parameter, DELTA, related with the hopping from the f states to the conduction ones. These U values are very similar for all compounds, about 7 eV, but the hybridization parameter slightly changes from 0.2 to 0.16 eV on increasing the Sn concentration. In Sn-rich compounds, the 4f occupation is close to spin limit fluctuation, which allows us to obtain an estimation of the Kondo temperatures, approx1200 K, and the static 0 K susceptibility, approx1.1x10{sup -3} emu/mol. Finally, we have done 'ab-initio' calculations based on the LDA+U+SO which confirm the existence of a small electronic gap opening in the DOS of Ge-rich compounds for U values lower than 7 eV.

Misoprostol inhibits gastric mucosal release of endogenous prostaglandin E2 and thromboxane B2 in healthy volunteers

DEFF Research Database (Denmark)

Mertz-Nielsen, A; Eskerod, O; Bukhave, K

1995-01-01

Prostaglandin analogues of the E-series theoretically offer the ideal antiulcer drugs. Peptic ulcer healing with prostaglandin analogues is, however, no better than would be predicted from their ability to inhibit gastric acid secretion and they are less effective than histamine H2 receptor...... antagonists in preventing ulcer relapse. It could be that prostaglandin analogues inhibit gastric mucosal synthesis or release of endogenous eicosanoids, thereby abrogating their own effects. This study, therefore, examined how a single therapeutic dose (200 micrograms) of misoprostol, a synthetic analogue...... blind, cross over design. In each subject misoprostol or placebo was instilled in randomised order into the stomach, which was subsequently perfused with isotonic mannitol. Misoprostol significantly decreased basal as well as acid stimulated output of PGE2 and TXB2, without affecting output of LTB4...

Solute concentration affects bradykinin-mediated increases in renal prostaglandin E2

International Nuclear Information System (INIS)

Zenser, T.V.; Davis, E.S.; Rapp, N.S.; Davis, B.B.

1981-01-01

The effects of solute concentration on the bradykinin-mediated increase in inner medullary slice prostaglandin E2 (PGE2) synthesis were investigated. PG content was determined by specific RIA. Bradykinin stimulation was prevented by the addition of the following solutes to Krebs buffer: 1.0 M urea, 0.5 or 1.0 M NaCl, 0.5 or 1.0 M mannitol, 1.0 M urea plus 0.5 M NaCl, or 1.0 M mannitol plus 0.5 M NaCl. By contrast, basal PGE2 synthesis was increased by 1.0 M mannitol or by 1.0 M mannitol plus 0.5 M NaCl, but decreased by 1.0 M urea. Urea elicited a concentration-dependent, reversible inhibition of bradykinin stimulation, with 0.01 M urea being the lowest effective concentration. By contrast, basal PGE2 synthesis was only reduced at a urea concentration greater than 0.6 M. Arachidonic acid-mediated increases in both PGE2 and PGF2 alpha synthesis were not prevented by 1.0 M urea. The latter suggests that neither PG endoperoxide synthetase nor PG endoperoxide E isomerase are inhibited by urea. The data indicate that different hypertonic solutions have different effects on basal PG production, but all inhibit bradykinin stimulation

Polysubstituted 4,6-bis(hetero)arylpyrimidines as dual inhibitors of nitric oxide and prostaglandin E-2 production

Czech Academy of Sciences Publication Activity Database

Kolman, Viktor; Jansa, Petr; Kalčic, Filip; Janeba, Zlatko; Zídek, Zdeněk

2017-01-01

Roč. 67, Jul 1 (2017), s. 53-57 ISSN 1089-8603 R&D Projects: GA TA ČR(CZ) TE01020028 Institutional support: RVO:61388963 ; RVO:68378041 Keywords : pyrimidine derivatives * nitric oxide * prostaglandin E-2 * dual inhibitors * anti-inflammatory properties Subject RIV: CE - Biochemistry; CC - Organic Chemistry (UEM-P) OBOR OECD: Biochemistry and molecular biology; Organic chemistry (UEM-P) Impact factor: 4.181, year: 2016

Novel contraceptive targets to inhibit ovulation: the prostaglandin E2 pathway.

Science.gov (United States)

Duffy, Diane M

2015-01-01

Prostaglandin E2 (PGE2) is an essential intrafollicular regulator of ovulation. In contrast with the one-gene, one-protein concept for synthesis of peptide signaling molecules, production and metabolism of bioactive PGE2 requires controlled expression of many proteins, correct subcellular localization of enzymes, coordinated PGE2 synthesis and metabolism, and prostaglandin transport in and out of cells to facilitate PGE2 action and degradation. Elevated intrafollicular PGE2 is required for successful ovulation, so disruption of PGE2 synthesis, metabolism or transport may yield effective contraceptive strategies. This review summarizes case reports and studies on ovulation inhibition in women and macaques treated with cyclooxygenase inhibitors published from 1987 to 2014. These findings are discussed in the context of studies describing levels of mRNA, protein, and activity of prostaglandin synthesis and metabolic enzymes as well as prostaglandin transporters in ovarian cells. The ovulatory surge of LH regulates the expression of each component of the PGE2 synthesis-metabolism-transport pathway within the ovulatory follicle. Data from primary ovarian cells and cancer cell lines suggest that enzymes and transporters can cooperate to optimize bioactive PGE2 levels. Elevated intrafollicular PGE2 mediates key ovulatory events including cumulus expansion, follicle rupture and oocyte release. Inhibitors of the prostaglandin-endoperoxide synthase 2 (PTGS2) enzyme (also known as cyclooxygenase-2 or COX2) reduce ovulation rates in women. Studies in macaques show that PTGS2 inhibitors can reduce the rates of cumulus expansion, oocyte release, follicle rupture, oocyte nuclear maturation and fertilization. A PTGS2 inhibitor reduced pregnancy rates in breeding macaques when administered to simulate emergency contraception. However, PTGS2 inhibition did not prevent pregnancy in monkeys when administered to simulate monthly contraceptive use. PTGS2 inhibitors alone may be suitable

Peri-OVLT E-series prostaglandins and core temperature do not increase after intravenous IL-1beta in pregnant rats.

Science.gov (United States)

Fewell, James E; Eliason, Heather L; Auer, Roland N

2002-08-01

Rats have an attenuated febrile response to endogenous pyrogen near the term of pregnancy. Given the fundamental role of E-series prostaglandins (PGEs) in mediating the febrile response to blood-borne endogenous pyrogen, the present experiments were carried out to determine whether PGEs increase in the area surrounding the organum vasculosum laminae terminalis (peri-OVLT) of near-term pregnant (P) rats as in nonpregnant (NP) rats after intravenous (iv) administration of recombinant rat interleukin-1beta (rrIL-1beta). Core temperature was measured by telemetry and peri-OVLT interstitial fluid was sampled in 12 NP and 12 P chronically instrumented, Sprague-Dawley rats by microdialysis for determination of total PGEs by radioimmunoassay. Basal core temperatures were higher in NP compared with P rats (NP 37.9 degrees C +/- 0.5, P 36.9 degrees C +/- 0.4; P endogenous pyrogen near the term of pregnancy, warrants further investigation.

15-Deoxy-delta12,14-prostaglandin J2, a neuroprotectant or a neurotoxicant?

International Nuclear Information System (INIS)

Koh, Seong-Ho; Jung, Boo; Song, Chi Won; Kim, Youngchul; Kim, Yong Soon; Kim, Seung Hyun

2005-01-01

15-Deoxy-delta12,14-prostaglandin J2 (15d-PGJ2) is a potent ligand for peroxisome proliferators-activated receptor γ (PPARγ). However, its various effects independent of PPARγ have recently been observed. The effect of 15d-PGJ2 on neuronal cells is still controversial. We investigated its effect on neuronal cells (N18D3 cells). When N18D3 cells were treated with 15d-PGJ2, the viability was not changed up to 8 μM, but decreased at higher than 8 μM. The expressions of survival signals, such as p85a phosphatidylinositol 3-kinase, phospho-Akt, and phospho-glycogen synthase kinase-3 beta (Ser-9), slightly increased up to 8 μM, however, decreased at higher than 8 μM. The levels of free radicals and membrane lipid peroxidation and the expression of c-Jun N-terminal Kinase increased in a dose-dependent manner, especially at higher than 8 μM. However, the expressions of death signals, such as cytosolic cytochrome c, activated caspase-3, and cleaved poly(ADP-ribose) polymerase, decreased up to 8 μM, however, increased at higher than 8 μM. In the study to evaluate whether low dose of 15d-PGJ2, up to 8 μM, had protective effect on oxidative stress-injured N18D3 cells, compared to the cells treated with only 100 μM H 2 O 2 , the pretreatment with 8 μM 15d-PGJ2 increased the viability and the expressions of the survival signals, but decreased them of the death signals. These results indicate that 15d-PGJ2 could be a neuroprotectant or a neurotoxicant, depending on its concentration. Therefore, some specific optimum dose of 15d-PGJ2 may be a new potential therapeutic candidate for oxidative stress-injury model of neurodegenerative diseases

Oligonol supplementation attenuates body temperature and the circulating levels of prostaglandin E2 and cyclooxygenase-2 after heat stress in humans.

Science.gov (United States)

Shin, Young Oh; Lee, Jeong Beom; Song, Young Ju; Min, Young Ki; Yang, Hun Mo

2013-04-01

Oligonol, a phenolic production from lychee, has been reported to exhibit anti-oxidative and anti-inflammatory effects. This study investigated the effect of Oligonol supplementation on circulating levels of prostaglandin E2 (PGE2) and cyclooxygenase (COX)-2, as well as body temperature, after heat stress in 17 healthy human male volunteers (age, 21.6±2.1 years). All experiments were performed in an automated climate chamber (26.0°C±0.5°C, relative humidity 60%±3.0%, air velocity less than 1 m/sec) between 2 and 5 p.m. Subjects ingested an Oligonol (100 mg)-containing beverage or placebo beverage before half-body immersion into hot water (42°C±0.5°C for 30 min). Tympanic and skin temperatures were measured and mean body temperatures were calculated. Serum concentrations of PGE2 and COX-2 were analyzed before, immediately after, and 60 min after immersion. Oligonol intake significantly prevented elevation of tympanic (temperature difference: 0.17°C at Post, Pbody temperatures (temperature difference: 0.18°C at Post, Pbody temperature under heat stress, and this is associated with decreases in serum levels of PGE2 and COX-2.

Multimode delta-E effect magnetic field sensors with adapted electrodes

Energy Technology Data Exchange (ETDEWEB)

Zabel, Sebastian; Fichtner, Simon; Kirchhof, Christine; Quandt, Eckhard; Faupel, Franz, E-mail: ff@tf.uni-kiel.de [Faculty of Engineering, Institute for Materials Science, Kiel University, Kaiserstraße 2, 24143 Kiel (Germany); Reermann, Jens; Schmidt, Gerhard [Faculty of Engineering, Institute for Electrical Engineering, Kiel University, Kaiserstraße 2, 24143 Kiel (Germany); Wagner, Bernhard [Fraunhofer Institute for Silicon Technology ISIT, Fraunhoferstraße 1, 25524 Itzehoe (Germany)

2016-05-30

We present an analytical and experimental study on low-noise piezoelectric thin film resonators that utilize the delta-E effect of a magnetostrictive layer to measure magnetic fields at low frequencies. Calculations from a physical model of the electromechanical resonator enable electrode designs to efficiently operate in the first and second transversal bending modes. As predicted by our calculations, the adapted electrode design improves the sensitivity by a factor of 6 and reduces the dynamic range of the sensor output by 16 dB, which significantly eases the requirements on readout electronics. Magnetic measurements show a bandwidth of 100 Hz at a noise level of about 100 pTHz{sup −0.5}.

Dual inhibition of nitric oxide and prostaglandin E2 production by polysubstituted 2-aminopyrimidines

Czech Academy of Sciences Publication Activity Database

Zídek, Zdeněk; Kverka, Miloslav; Dusilová, Adéla; Kmoníčková, Eva; Jansa, Petr

2016-01-01

Roč. 57, jul (2016), s. 48-56 ISSN 1089-8603 R&D Projects: GA ČR(CZ) GAP303/12/0172 Institutional support: RVO:68378041 ; RVO:61388963 Keywords : pyrimidines * nitric oxide * prostaglandin E-2 Subject RIV: FR - Pharmacology ; Medidal Chemistry; CC - Organic Chemistry (UOCHB-X) Impact factor: 4.181, year: 2016

In vivo formation of beta-oxidized metabolites of leukotriene E4 in the rat

International Nuclear Information System (INIS)

Perrin, P.; Zirrolli, J.; Stene, D.O.; Lellouche, J.P.; Beaucourt, J.P.; Murphy, R.C.

1989-01-01

Intraperitoneal administration of [ 3 H]-leukotriene E4 in the rat resulted in the appearance of radiolabel in urine and feces. Separation of polar urinary metabolites and chromatographic comparison of synthetic metabolites indicated the in vivo formation of omega-oxidized metabolites of LTE4 with sequential beta-oxidation. Furthermore, the metabolite identified as 16-carboxy-17,18,19,20-tetranor-14,15-dihydro-N-acetyl-LTE4 substantiates the biochemical pathway of beta-oxidation in vivo involving the 2,4-dienoyl CoA reductase as an integral step. These results substantiate beta-oxidation of sulfidopeptide leukotrienes in vivo and these metabolites account for some of the major urinary metabolites of this class of lipid mediator

COMMD1 regulates the delta epithelial sodium channel ({delta}ENaC) through trafficking and ubiquitination

Energy Technology Data Exchange (ETDEWEB)

Chang, Tina; Ke, Ying; Ly, Kevin [Department of Physiology, University of Otago, P.O. Box 913, Dunedin 9054 (New Zealand); McDonald, Fiona J., E-mail: fiona.mcdonald@otago.ac.nz [Department of Physiology, University of Otago, P.O. Box 913, Dunedin 9054 (New Zealand)

2011-08-05

Highlights: {yields} The COMM domain of COMMD1 mediates binding to {delta}ENaC. {yields} COMMD1 reduces the cell surface population of {delta}ENaC. {yields} COMMD1 increases the population of {delta}ENaC-ubiquitin. {yields} Both endogenous and transfected {delta}ENaC localize with COMMD1 and transferrin suggesting they are located in early/recycling endosomes. -- Abstract: The delta subunit of the epithelial sodium channel ({delta}ENaC) is a member of the ENaC/degenerin family of ion channels. {delta}ENaC is distinct from the related {alpha}-, {beta}- and {gamma}ENaC subunits, known for their role in sodium homeostasis and blood pressure control, as {delta}ENaC is expressed in brain neurons and activated by external protons. COMMD1 (copper metabolism Murr1 domain 1) was previously found to associate with and downregulate {delta}ENaC activity. Here, we show that COMMD1 interacts with {delta}ENaC through its COMM domain. Co-expression of {delta}ENaC with COMMD1 significantly reduced {delta}ENaC surface expression, and led to an increase in {delta}ENaC ubiquitination. Immunocytochemical and confocal microscopy studies show that COMMD1 promoted localization of {delta}ENaC to the early/recycling endosomal pool where the two proteins were localized together. These results suggest that COMMD1 downregulates {delta}ENaC activity by reducing {delta}ENaC surface expression through promoting internalization of surface {delta}ENaC to an intracellular recycling pool, possibly via enhanced ubiquitination.

Efficiency, safety, and patient preference of switching from dorzolamide 1%/timolol 0.5% to brinzolamide 1%/timolol 0.5% while maintaining the prostaglandin F2α analog.

Science.gov (United States)

Shimizu, Yoshie; Nakakura, Shunsuke; Nishiyama, Makiko; Tabuchi, Hitoshi; Kiuchi, Yoshiaki

2015-01-01

We investigated the efficiency, safety and patient preference of switching from dorzolamide 1%/timolol 0.5% to brinzolamide 1%/timolol 0.5% while maintaining the prostaglandin F2α analog. We initially enrolled 44 eyes from 44 primary open angle glaucoma patients, and a total of 42 patients completed the study. All patients were under treatment with various prostaglandin F2α analogs and dorzolamide 1%/timolol 0.5%. While maintaining the prostaglandin F2α analog, dorzolamide 1%/timolol 0.5% was switched to brinzolamide 1%/timolol 0.5%. Conjunctival hyperemia, superficial punctate keratopathy, and intraocular pressure (IOP) were evaluated at baseline and at 4, 12, and 24 weeks. Adverse events and patient preferences, measured using a questionnaire at study initiation and at 24 weeks, were also noted. The IOP was 17.7±1.7, 16.8±2.6, 16.7±2.2, and 16.7±2.4 mmHg at baseline and at 4, 12, and 24 weeks, respectively, with no significant differences in IOP values at any time point (P=0.117, one-way analysis of variance). In addition, no significant differences were found in the incidence of conjunctival hyperemia or SPK score at any time point (all P>0.5, by Kruskal-Wallis test). Based on the evaluation of side effects using the questionnaire, stinging/burning was less common (P=0.042), while blurred vision was more common (P=0.003), after switching to brinzolamide 1%/timolol 0.5%. Regarding patient preferences, 13 patients (31%) preferred dorzolamide 1%/timolol 0.5%, 12 patients (29%) preferred brinzolamide 1%/timolol 0.5%, and 17 patients (40%) preferred neither. When switching from dorzolamide 1%/timolol 0.5% to brinzolamide 1%/timolol 0.5%, the IOP values and incidence of superficial punctate keratopathy and conjunctival hyperemia were sustained throughout the 24-week observation period, and the patient preferences were similar for the two regimens. However, differences were observed in the ocular sensations of stinging/burning with dorzolamide 1%/timolol 0

Prostaglandins - universal biological regulators in the human body (literature review

Directory of Open Access Journals (Sweden)

О. V. Tymoshchuk

2018-02-01

Full Text Available Recently, researchers of different industries pay great attention to the problem of prostaglandins. Objective: to study and systematize the basic questions of structure, biological action and metabolism of prostaglandins in the human body and using their analogues in pharmacy through the domestic and foreign literature data analysis. Prostaglandins – biologically active substances which are similar in effect to hormones, but are synthesized in cells of different tissues. Prostaglandins as universal cellular mediators are widely distributed in the body, synthesized in small amounts in almost all tissues, have both local and systemic effects. For each prostaglandin there is a target organ. On chemical structure they are small molecules related to eicosanoids - a group of fat-like substances (lipids. Depending on the chemical structure prostaglandins are divided into series (A, B, C, D, E, F, G, H, I and J and three groups (1–3; type F isomers are to be indicated by additional letters α and β. Prostaglandins have an extremely wide range of physiological effects in the body and have three main functions: supporting, molecular, neurotransmitter. Most prostaglandins interact with specific receptors of plasma membranes, but some prostaglandins (group A can act without receptors. There is no stock of prostaglandins in the body, their life cycle is short, and they are quickly produced in response to biological stimulants exposure, have their effect in extremely small quantity and are rapidly inactivated in the bloodstream. Due to the extremely rapid breakdown of prostaglandins in the body they work near their place of secretion. Preparations of prostaglandins and their derivatives are used in experimental and clinical medicine for abortion and induction of labor, treatment of stomach ulcers, asthma, certain heart diseases, congenital heart defects in newborns, glaucoma, atherosclerosis, rheumatic and neurological diseases, kidney diseases, diabetes

The influence of some prostaglandins on DNA synthesis and DNA excision repair in mouse spleen cells ''in vitro''

International Nuclear Information System (INIS)

Klein, W.; Altmann, H.; Kocsis, F.; Egg, D.; Guenther, R.

1978-03-01

''In vitro'' experiments were performed on mouse spleen cells to establish possible influences of some naturally occurring prostaglandins on DNA synthesis and DNA excision repair. The prostaglandins A 1 , B 1 , E 1 , E 2 and Fsub(2α) were tested in concentrations of 10 pg, 5 ng and 2,5μg per ml cell suspension. DNA synthesis was significantly increased by PgFsub(2α) in all the three concentrations tested, while the other tested prostaglandins were essentially ineffective. DNA excision repair was significantly inhibited by PgE 1 and PgE 2 at 5 ng/ml and at 2,5 μg/ml but increased by PgFsub(2α) in the two lower concentrations. The rejoining of DNA-strand breaks after gamma-irradiation was slightly reduced by PgE 1 , PgE 2 and PgF 2 at 2,5 μg/ml. (author)

Prostaglandin E(2) mediates acid-induced heartburn in healthy volunteers.

Science.gov (United States)

Kondo, Takashi; Oshima, Tadayuki; Tomita, Toshihiko; Fukui, Hirokazu; Watari, Jiro; Okada, Hiroki; Kikuchi, Shojiro; Sasako, Mitsuru; Matsumoto, Takayuki; Knowles, Charles H; Miwa, Hiroto

2013-03-15

Prostaglandin E(2) (PGE(2)) plays a major role in pain processing and hypersensitivity. This study investigated whether PGE(2) levels are increased in the esophageal mucosa after acid infusion and whether increases in PGE(2) are associated with heartburn. Furthermore, expression of the PGE(2) receptor EP1 was investigated in human esophageal mucosa. Fourteen healthy male volunteers were randomized to 30-min lower esophageal acid (1% HCl) or saline perfusion. Before and after acid perfusion, endoscopic biopsies were taken from the distal esophagus. PGE(2) concentration (pg/mg protein) and EP1 mRNA and protein in biopsy samples were measured by ELISA, RT-PCR, and Western blotting. Symptom status of heartburn was evaluated with a validated categorical rating scale with a higher values corresponding to increasing intensity. PGE(2) levels in the esophageal mucosa significantly increased after acid infusion (before vs. after acid infusion: 23.2 ± 8.6 vs. 68.6 ± 18.3, P heartburn in the acid-infusion group was also significantly greater compared with saline (saline vs. acid infusion: 54.3 ± 13.1 vs. 178.5 ± 22.8, P heartburn.

Rocuronium Bromide Inhibits Inflammation and Pain by Suppressing Nitric Oxide Production and Enhancing Prostaglandin E2 Synthesis in Endothelial Cells.

Science.gov (United States)

Baek, Sang Bin; Shin, Mal Soon; Han, Jin Hee; Moon, Sang Woong; Chang, Boksoon; Jeon, Jung Won; Yi, Jae Woo; Chung, Jun Young

2016-12-01

Rocuronium bromide is a nondepolarizing neuromuscular blocking drug and has been used as an adjunct for relaxation or paralysis of the skeletal muscles, facilitation of endotracheal intubation, and improving surgical conditions during general anesthesia. However, intravenous injection of rocuronium bromide induces injection pain or withdrawal movement. The exact mechanism of rocuronium bromide-induced injection pain or withdrawal movement is not yet understood. We investigated whether rocuronium bromide treatment is involved in the induction of inflammation and pain in vascular endothelial cells. For this study, calf pulmonary artery endothelial (CPAE) cells were used, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Western blot, nitric oxide detection, and prostaglandin E 2 immunoassay were conducted. Rocuronium bromide treatment inhibited endothelial nitric oxide synthase and suppressed nitric oxide production in CPAE cells. Rocuronium bromide activated cyclooxygenase-2, inducible nitric oxide synthase and increased prostaglandin E 2 synthesis in CPAE cells. Rocuronium bromide induced inflammation and pain in CPAE cells. Suppressing nitric oxide production and enhancing prostaglandin E 2 synthesis might be associated with rocuronium bromide-induced injection pain or withdrawal movement.

New insights into the catalytic mechanism of Bombyx mori prostaglandin E synthase gained from structure–function analysis

Energy Technology Data Exchange (ETDEWEB)

Yamamoto, Kohji, E-mail: yamamok@agr.kyushu-u.ac.jp [Faculty of Agriculture, Kyushu University Graduate School, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan); Suzuki, Mamoru; Higashiura, Akifumi [Institute for Protein Research, Osaka University, Suita 565-0871 (Japan); Aritake, Kosuke; Urade, Yoshihiro; Uodome, Nobuko [Department of Molecular Behavioral Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874 (Japan); Hossain, MD. Tofazzal [Faculty of Agriculture, Kyushu University Graduate School, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan); Nakagawa, Atsushi [Institute for Protein Research, Osaka University, Suita 565-0871 (Japan)

2013-11-01

Highlights: •Structure of Bombyx mori prostaglandin E synthase is determined. •Bound glutathione sulfonic acid is located at the glutathione-binding site. •Electron-sharing network is present in this protein. •This network includes Asn95, Asp96, and Arg98. •Site-directed mutagenesis reveals that the residues contribute to the catalytic activity. -- Abstract: Prostaglandin E synthase (PGES) catalyzes the isomerization of PGH{sub 2} to PGE{sub 2}. We previously reported the identification and structural characterization of Bombyx mori PGES (bmPGES), which belongs to Sigma-class glutathione transferase. Here, we extend these studies by determining the structure of bmPGES in complex with glutathione sulfonic acid (GTS) at a resolution of 1.37 Å using X-ray crystallography. GTS localized to the glutathione-binding site. We found that electron-sharing network of bmPGES includes Asn95, Asp96, and Arg98. Site-directed mutagenesis of these residues to create mutant forms of bmPGES mutants indicate that they contribute to catalytic activity. These results are, to our knowledge, the first to reveal the presence of an electron-sharing network in bmPGES.

Noggin and BMP4 co-modulate adult hippocampal neurogenesis in the APP{sub swe}/PS1{sub {Delta}E9} transgenic mouse model of Alzheimer's disease

Energy Technology Data Exchange (ETDEWEB)

Tang, Jun [Department of Medical Genetics, Third Military Medical University, Chongqing 400038 (China); Department of Physiology, Third Military Medical University, Chongqing 400038 (China); Song, Min; Wang, Yanyan [Department of Medical Genetics, Third Military Medical University, Chongqing 400038 (China); Fan, Xiaotang [Department of Histology and Embryology, Third Military Medical University, Chongqing 400038 (China); Xu, Haiwei, E-mail: haiweixu2001@yahoo.com.cn [Department of Physiology, Third Military Medical University, Chongqing 400038 (China); Bai, Yun, E-mail: baiyungene@gmail.com [Department of Medical Genetics, Third Military Medical University, Chongqing 400038 (China)

2009-07-31

In addition to the subventricular zone, the dentate gyrus of the hippocampus is one of the few brain regions in which neurogenesis continues into adulthood. Perturbation of neurogenesis can alter hippocampal function, and previous studies have shown that neurogenesis is dysregulated in Alzheimer disease (AD) brain. Bone morphogenetic protein-4 (BMP4) and its antagonist Noggin have been shown to play important roles both in embryonic development and in the adult nervous system, and may regulate hippocampal neurogenesis. Previous data indicated that increased expression of BMP4 mRNA within the dentate gyrus might contribute to decreased hippocampal cell proliferation in the APP{sub swe}/PS1{sub {Delta}E9} mouse AD model. However, it is not known whether the BMP antagonist Noggin contributes to the regulation of neurogenesis. We therefore studied the relative expression levels and localization of BMP4 and its antagonist Noggin in the dentate gyrus and whether these correlated with changes in neurogenesis in 6-12 mo old APP{sub swe}/PS1{sub {Delta}E9} transgenic mice. Bromodeoxyuridine (BrdU) was used to label proliferative cells. We report that decreased neurogenesis in the APP/PS1 transgenic mice was accompanied by increased expression of BMP4 and decreased expression of Noggin at both the mRNA and protein levels; statistical analysis showed that the number of proliferative cells at different ages correlated positively with Noggin expression and negatively with BMP4 expression. Intraventricular administration of a chimeric Noggin/Fc protein was used to block the action of endogenous BMP4; this resulted in a significant increase in the number of BrdU-labeled cells in dentate gyrus subgranular zone and hilus in APP/PS1 mice. These results suggest that BMP4 and Noggin co-modulate neurogenesis.

Perspective of microsomal prostaglandin E2 synthase-1 as drug target in inflammation-related disorders.

Science.gov (United States)

Koeberle, Andreas; Werz, Oliver

2015-11-01

Prostaglandin (PG)E2 encompasses crucial roles in pain, fever, inflammation and diseases with inflammatory component, such as cancer, but is also essential for gastric, renal, cardiovascular and immune homeostasis. Cyclooxygenases (COX) convert arachidonic acid to the intermediate PGH2 which is isomerized to PGE2 by at least three different PGE2 synthases. Inhibitors of COX - non-steroidal anti-inflammatory drugs (NSAIDs) - are currently the only available therapeutics that target PGE2 biosynthesis. Due to adverse effects of COX inhibitors on the cardiovascular system (COX-2-selective), stomach and kidney (COX-1/2-unselective), novel pharmacological strategies are in demand. The inducible microsomal PGE2 synthase (mPGES)-1 is considered mainly responsible for the excessive PGE2 synthesis during inflammation and was suggested as promising drug target for suppressing PGE2 biosynthesis. However, 15 years after intensive research on the biology and pharmacology of mPGES-1, the therapeutic value of mPGES-1 as drug target is still vague and mPGES-1 inhibitors did not enter the market so far. This commentary will first shed light on the structure, mechanism and regulation of mPGES-1 and will then discuss its biological function and the consequence of its inhibition for the dynamic network of eicosanoids. Moreover, we (i) present current strategies for interfering with mPGES-1-mediated PGE2 synthesis, (ii) summarize bioanalytical approaches for mPGES-1 drug discovery and (iii) describe preclinical test systems for the characterization of mPGES-1 inhibitors. The pharmacological potential of selective mPGES-1 inhibitor classes as well as dual mPGES-1/5-lipoxygenase inhibitors is reviewed and pitfalls in their development, including species discrepancies and loss of in vivo activity, are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

AUGMENTATIVE EFFECT OF PROSTAGLANDIN E1 ON PENTOBARBITAL HYPNOSIS MEDIATED BY 5-HT IN CHICKS

Directory of Open Access Journals (Sweden)

Amalendu Chanda

2012-01-01

Full Text Available Prostaglandins (PG are present in different tissues specially in brain tissues endowed with different central nervous system activities. Similarly, 5-hydroxytryptamine (5-HT a biogenic amine with its presence in different central and peripheral tissues as neurotransmitter plays an important role in the regulation of physiological functions specially hypnosis, convulsions, analgesia in rats, mice, cats and chicks etc. Pentobarbitone (PB induced sleep appear to be a serotonergic modulator activity in different animals. PGE1 potentiates the pentobarbitone hypnosis also mediated through serotonin. In the present study, PGE1 induced sleeping time in chicks was evaluated. Drugs affecting 5-HT synthesis, metabolism and receptor activity modulate the potentiating response, while adrenergic receptor antagonists did not showed any response. This study suggest that PGE1 potentiate PB induced sleep through serotonergic signaling pathway as PGE1 increased 5-HT synthesis rate in chick brain.

Prostaglandin E (dmPGE{sub 2}) action in vitro on the activity of rat liver Golgi apparatus galactosyltransferase

Energy Technology Data Exchange (ETDEWEB)

Kordowiak, A.M.; Tomecki, J.; Procyk, K.; Kapusta, P. [Uniwersytet Jagiellonski, Cracow (Poland)

1993-12-31

In vitro addition of 16,16`-dimethyl prostaglandin E{sub 2} to Golgi-rich membrane fraction in final concentration of 0.1 {mu}g/1 mg of protein increased generally the activity of galactosyltransferase in comparison with control. The percentage of phospholipids in the whole fraction was similar in both investigated groups, only the sum of phosphatidylenoamine + phosphatidic acid was significantly lower after addition of dmPGE{sub 2} than in the control (0.001 < P < 0.01). (author). 25 refs, 2 figs, 1 tab.

Problems connected with the production of highly specific antisera against prostaglandin E2 (PGE2) and prostaglandin A2 (PGA2) for radioimmunoassay

International Nuclear Information System (INIS)

Kopp, H.G.; Vetter, W.; Siegenthaler, W.

1978-01-01

To obtain sensitive and specific antisera against PGE 2 and PGA 2 these substances were coupled to thyroglobulin (Tg). Coupling reactions were performed by using either a hydroxy-succinimide-ester as intermediate step leading to a complex carrying 170mol PGE 2 per mol Tg (''PGE 2 -OSU-Tg'') and 240mol PGA 2 per mol Tg (''PGA 2 -OSU-Tg''), or N, N'-carbonyl-diimidazole resulting in ''PGE 2 -CDI-Tg'' (400mol PGE 2 per mol Tg) and ''PGA 2 -CDI-Tg'' (600mol PGA 2 per mol Tg). Two tracer systems ( 3 H-prostaglandin and 125 I-histamine-prostaglandin) were used for analysis of antibody activity. The PGE 2 -CDI-Tg and PGA 2 -CDI-Tg complexes were both poor immunogens in rabbits. The PGE 2 -OSU-Tg and PGA 2 -OSU-Tg conjugates were injected in rabbits and in guinea-pigs. These two compounds resulted in very high antibody titres in both animal species. However, in guinea-pigs a markedly higher antibody sensitivity and antibody specificity were observed than in rabbits. Our results indicate that the guinea-pig may be the animal of choice for immunization against prostaglandins. Antibody specificity of guinea-pig antisera may be high enough to measure the concentration of PGE 2 and PGA 2 in the presence of other prostaglandins or prostaglandin metabolites. (author)

Problems connected with the production of highly specific antisera against prostaglandin E2 (PGE2) and prostaglandin A2 (PGA2) for radioimmunoassay

International Nuclear Information System (INIS)

Kopp, H.G.; Vetter, W.; Siegenthaler, W.

1977-01-01

To obtain sensitive and specific antisera against PGE 2 and PGA 2 these substances were coupled to thyroglobulin (Tg). Coupling reactions were either performed by using a hydroxysuccinimideester as intermediate step leading to a complex carrying 170 mol PGE 2 per mol Tg ('PGE 2 -OSU-Tg') and 240 mol PGA 2 per mol Tg ('PGA 2 -OSU-Tg') or alternatively by using N,N'-carbonyl-diimidazole resulting in 'PGE 2 -CDI-Tg' (400 mol PGE 2 per mol Tg) and 'PGA 2 -CDI-Tg' (600 mol PGA 2 per mol Tg). Two tracer systems ( 3 H-prostaglandin, 125 I-histamine-prostaglandin) were used for analysis of antibody activity. Both PGE 2 - and PGA 2 -CDI-Tg complexes were poor immunogens in rabbits. The PGE 2 - and PGA 2 -OSU-Tg conjugates were injected both in rabbits and in guinea pigs. These two compounds resulted in very high antibody titers in both animal species. However, in guinea pigs markedly higher antibody sensitivity and antibody specificity were observed than in rabbits. Our results indicate that the guinea pig may be the animal of choice for immunization against prostaglandins. Antibody specificity of guinea pig antisera may be perhaps high enough to measure the concentration of PGE 2 and PGA 2 in the presence of other prostaglandins or prostaglandin metabolites. (orig.) [de

Dominant role of prostaglandin E2 EP4 receptor in furosemide-induced salt-losing tubulopathy: a model for hyperprostaglandin E syndrome/antenatal Bartter syndrome

DEFF Research Database (Denmark)

Nüsing, Rolf M; Treude, Antje; Weissenberger, Christian

2005-01-01

Increased formation of prostaglandin E2 (PGE2) is a key part of hyperprostaglandin E syndrome/antenatal Bartter syndrome (HPS/aBS), a renal disease characterized by NaCl wasting, water loss, and hyperreninism. Inhibition of PGE2 formation by cyclo-oxygenase inhibitors significantly lowers patient...

17 CFR 240.14e-1 - Unlawful tender offer practices.

Science.gov (United States)

2010-04-01

... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Unlawful tender offer... Securities Exchange Act of 1934 Regulation 14e § 240.14e-1 Unlawful tender offer practices. As a means... section 14(e) of the Act, no person who makes a tender offer shall: (a) Hold such tender offer open for...

Prostaglandin E1 and Its Analog Misoprostol Inhibit Human CML Stem Cell Self-Renewal via EP4 Receptor Activation and Repression of AP-1.

Science.gov (United States)

Li, Fengyin; He, Bing; Ma, Xiaoke; Yu, Shuyang; Bhave, Rupali R; Lentz, Steven R; Tan, Kai; Guzman, Monica L; Zhao, Chen; Xue, Hai-Hui

2017-09-07

Effective treatment of chronic myelogenous leukemia (CML) largely depends on the eradication of CML leukemic stem cells (LSCs). We recently showed that CML LSCs depend on Tcf1 and Lef1 factors for self-renewal. Using a connectivity map, we identified prostaglandin E1 (PGE1) as a small molecule that partly elicited the gene expression changes in LSCs caused by Tcf1/Lef1 deficiency. Although it has little impact on normal hematopoiesis, we found that PGE1 treatment impaired the persistence and activity of LSCs in a pre-clinical murine CML model and a xenograft model of transplanted CML patient CD34 + stem/progenitor cells. Mechanistically, PGE1 acted on the EP4 receptor and repressed Fosb and Fos AP-1 factors in a β-catenin-independent manner. Misoprostol, an FDA-approved EP4 agonist, conferred similar protection against CML. These findings suggest that activation of this PGE1-EP4 pathway specifically targets CML LSCs and that the combination of PGE1/misoprostol with conventional tyrosine-kinase inhibitors could provide effective therapy for CML. Copyright © 2017 Elsevier Inc. All rights reserved.

The Prostaglandin E2-EP3 Receptor Axis Regulates Anaplasma phagocytophilum-Mediated NLRC4 Inflammasome Activation.

Directory of Open Access Journals (Sweden)

Xiaowei Wang

2016-08-01

Full Text Available Rickettsial agents are sensed by pattern recognition receptors but lack pathogen-associated molecular patterns commonly observed in facultative intracellular bacteria. Due to these molecular features, the order Rickettsiales can be used to uncover broader principles of bacterial immunity. Here, we used the bacterium Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis, to reveal a novel microbial surveillance system. Mechanistically, we discovered that upon A. phagocytophilum infection, cytosolic phospholipase A2 cleaves arachidonic acid from phospholipids, which is converted to the eicosanoid prostaglandin E2 (PGE2 via cyclooxygenase 2 (COX2 and the membrane associated prostaglandin E synthase-1 (mPGES-1. PGE2-EP3 receptor signaling leads to activation of the NLRC4 inflammasome and secretion of interleukin (IL-1β and IL-18. Importantly, the receptor-interacting serine/threonine-protein kinase 2 (RIPK2 was identified as a major regulator of the immune response against A. phagocytophilum. Accordingly, mice lacking COX2 were more susceptible to A. phagocytophilum, had a defect in IL-18 secretion and exhibited splenomegaly and damage to the splenic architecture. Remarkably, Salmonella-induced NLRC4 inflammasome activation was not affected by either chemical inhibition or genetic ablation of genes associated with PGE2 biosynthesis and signaling. This divergence in immune circuitry was due to reduced levels of the PGE2-EP3 receptor during Salmonella infection when compared to A. phagocytophilum. Collectively, we reveal the existence of a functionally distinct NLRC4 inflammasome illustrated by the rickettsial agent A. phagocytophilum.

Microarray evaluation of EP4 receptor-mediated prostaglandin E2 suppression of 3T3-L1 adipocyte differentiation

International Nuclear Information System (INIS)

Sugimoto, Yukihiko; Tsuboi, Hiroaki; Okuno, Yasushi; Tamba, Shigero; Tsuchiya, Soken; Tsujimoto, Gozo; Ichikawa, Atsushi

2004-01-01

Prostaglandin E 2 (PGE 2 ) has been shown to negatively regulate adipogenesis. To explore to what extent PGE 2 inhibits the differentiation of cells to adipocytes and to examine whether its effect could be due to EP4 receptor signaling, we used microarrays to analyze the gene expression profiles of 3T3-L1 cells exposed to a differentiation cocktail supplemented with PGE 2 , AE1-329 (an EP4 agonist), or vehicle. The differentiation-associated responses in genes such as adipocytokines and enzymes related to lipid metabolism were largely weakened upon PGE 2 treatment. In particular, the expression of peroxisome proliferator activated receptor-γ and CCAAT/enhancer binding protein-α, genes playing a central role in adipogenesis, was greatly suppressed. PGE 2 appears to be ineffective to a subclass of insulin target genes such as hexokinase 2 and phosphofructokinase. Similar responses were produced in the differentiation-associated genes upon AE1-329 treatment. These results suggest that PGE 2 inhibits a crucial step of the adipocyte differentiation process by acting on the EP4 receptor in 3T3-L1 cells

99Tcm-MIBI imaging with liposomal prostaglandin E1 infusion to detect viable myocardium in post-myocardial infarction patients

International Nuclear Information System (INIS)

Zheng Yong; Cai Hongbin; Miao Weibing; Lin Jun; Pan Runyang; Lin Haoxue

2007-01-01

Objective: The pharmacological efficiencies of liposomal prostaglandin E 1 (Lipo-PGE 1 ) infusion and nitrate infusion on 99 Tc m -methoxyisobutylisonitrile (MIBI) imaging detection of viable myocardium in post-myocardial infarction (MI) patients were compared in the current study. Methods: Thirty-two patients with MI underwent 99 Tc m -MIBI imaging at rest, nitrate infusion and Lipo-PGE 1 infusion respectively. The semi-quantitative analysis of 99 Tc m -MIBI imaging was carried out in 16 segments over each left ventricle. Results: Abnormal 99 Tc m -MIBI distribution in 216 segments (42.2%) at rest, 178 segments (34.8%) at nitrate infusion, and 184 segments (35.9%) at Lipo-PGE 1 infusion were identified. Among the 216 abnormal segments at rest, 89 (41.2%) and 81 (37.5%) were found improved after nitrate infusion and Lipo-PGE 1 infusion respectively. Detecting viable myocardium with Lipo-PGE 1 infusion imaging was accordant with that of nitrate infusion imaging in 89.8% of the cases. The mean uptake scores of abnormal segments at rest, nitrate infusion, and Lipo-PGE 1 infusion were 15.3 ± 3.3, 10.5 ± 1.4 (P 1 infusion imaging can be used for detection of viable myocardium in patients with MI. (authors)

On-beam calibration of the {delta}E(Si)-Sci/PD charged particle telescope

Energy Technology Data Exchange (ETDEWEB)

Avdeichikov, V. E-mail: vladimir.Avdeichikov@kosufy.lu.se; Jakobsson, B.; Nikitin, V.A.; Nomokonov, P.V.; Veldhuizen, E.J. van

2001-07-11

The reaction products emitted in the {sup 14}N(45A MeV)+(CH{sub 2}/CD{sub 2}) interactions are identified by a {delta}E(Si)-E(Scintillator/Photodiode) telescope by the conventional {delta}E-E method. The position of 'jumps' in the amplitude of the photodiode signal for ions passing through the scintillator (Sci) is used to calibrate on-beam both the {delta}E and the Sci/PD scales in MeV. The accuracy of an absolute energy calibration is better than 2.3% and 1.8% for CsI(Tl) and GSO(Ce) detectors, respectively. It is defined mostly by the correctness of the range-energy relations of ions in the Si and Sci crystals. The light response function, L(E,Z,A), of isotopes up to Z(A)=8(16) in the range of energy {approx}(2.5-60)A MeV is extracted. The effects of doping concentration and pulse shaping on the light response are analyzed. The validity of the existing empirical light-energy relations is checked in a wide interval of ion energies and a new power law relation is proposed. Calculations of the response function based on the Murray-Mayer model are found to be in excellent agreement with experimental data for the CsI(Tl) crystal.

DELTAS: A new Global Delta Sustainability Initiative (Invited)

Science.gov (United States)

Foufoula-Georgiou, E.

2013-12-01

Deltas are economic and environmental hotspots, food baskets for many nations, home to a large part of the world population, and hosts of exceptional biodiversity and rich ecosystems. Deltas, being at the land-water interface, are international, regional, and local transport hubs, thus providing the basis for intense economic activities. Yet, deltas are deteriorating at an alarming rate as 'victims' of human actions (e.g. water and sediment reduction due to upstream basin development), climatic impacts (e.g. sea level rise and flooding from rivers and intense tropical storms), and local exploration (e.g. sand or aggregates, groundwater and hydrocarbon extraction). Although many efforts exist on individual deltas around the world, a comprehensive global delta sustainability initiative that promotes awareness, science integration, data and knowledge sharing, and development of decision support tools for an effective dialogue between scientists, managers and policy makers is lacking. Recently, the international scientific community proposed to establish the International Year of Deltas (IYD) to serve as the beginning of such a Global Delta Sustainability Initiative. The IYD was proposed as a year to: (1) increase awareness and attention to the value and vulnerability of deltas worldwide; (2) promote and enhance international and regional cooperation at the scientific, policy, and stakeholder level; and (3) serve as a launching pad for a 10-year committed effort to understand deltas as complex socio-ecological systems and ensure preparedness in protecting and restoring them in a rapidly changing environment. In this talk, the vision for such an international coordinated effort on delta sustainability will be presented as developed by a large number of international experts and recently funded through the Belmont Forum International Opportunities Fund. Participating countries include: U.S., France, Germany, U.K., India, Japan, Netherlands, Norway, Brazil, Bangladesh

Regulation of prostaglandin E2 synthesis after brain irradiation

International Nuclear Information System (INIS)

Moore, Amy H.; Olschowka, John A.; Williams, Jacqueline P.; Okunieff, Paul; O'Banion, M. Kerry

2005-01-01

Purpose: A local tissue reaction, termed neuroinflammation, occurs after irradiation of brain tissue. Previous work suggested that cyclooxygenase (COX)-2 activity was important for changes in gene expression associated with neuroinflammation as well as increased prostaglandin E 2 (PGE 2 ) levels seen after radiation treatment. Methods and materials: To begin to determine the contributions of other enzymes involved in PGE 2 production, we examined protein levels of COX-1 and COX-2 as well as 2 PGE synthases (membrane and cytosolic PGES) 4 h after 35 Gy single dose irradiation to the brains of C3HeN mice. We also evaluated the effects of specific COX inhibitors on PGE 2 production and PGES expression. Results: As expected, COX-2 expression increased after radiation exposure. Brain irradiation also increased tissue protein levels for both PGES isoforms. Specific COX-2 inhibition with NS398 lowered brain PGE 2 levels by about 60%. Surprisingly, COX-1 inhibition with SC560 completely prevented the elevation of PGE 2 seen after irradiation. Interestingly, NS398 reduced the membrane-associated PGES isoform, whereas SC560 treatment lowered cytosolic isoform levels below those seen in unirradiated controls. Conclusions: Taken together, these data indicate that both cyclooxygenases contribute to PGE 2 production in irradiated brain and reveal dependence of PGES isoforms expression on specific cyclooxygenase activities

Critical current density of strained multilayer thin films of Nd sub 1. 83 Ce sub 0. 17 CuO sub x /YBa sub 2 Cu sub 3 O sub 7 minus. delta

Energy Technology Data Exchange (ETDEWEB)

Gross, R.; Gupta, A.; Olsson, E.; Segmueller, A.; Koren, G. (IBM T. J. Watson Research Center, P.O. Box 218, Yorktown Heights, New York 10598 (USA))

1990-07-09

The superconducting transport properties of strained multilayer thin films of YBa{sub 2}Cu{sub 3}O{sub 7{minus}{delta}}/ Nd{sub 1.83}Ce{sub 0.17}CuO{sub {ital x}}, grown heteroepitaxially by laser ablation deposition, are reported. For individual layer thicknesses below a critical layer thickness of about 250 A, coherency strain removes the orthorhombic distortion in the YBa{sub 2}Cu{sub 3}O{sub 7{minus}{delta}} layers and makes them twin-free. Zero-field critical current densities as high as 1.1{times}10{sup 7} A/cm{sup 2} at 77 K have been measured for the YBa{sub 2}Cu{sub 3}O{sub 7{minus}{delta}} layers. Flux pinning energies at zero temperature and zero magnetic field in the range of 80--140 meV have been found.

Circulating prostacyclin metabolites in the dog

International Nuclear Information System (INIS)

Taylor, B.M.; Shebuski, R.J.; Sun, F.F.

1983-01-01

The present study was designed to determine the concentration of prostacyclin (PGI2) metabolites in the blood of the dog. After a bolus i.v. dose of [11 beta- 3 H]PGI2 (5 micrograms/kg) into each of five dogs, blood samples were withdrawn at 0.33, 0.67, 1, 3, 5, 20, 30, 60 and 120 min postdrug administration. Plasma samples were extracted and the radioactive components were analyzed by two-dimensional thin-layer chromatography with autoradiofluorography and radio-high-performance liquid chromatography. The compounds were identified by comparing their mobility with synthetic standards; only parallel responses observed in both tests constituted positive identification. Seven metabolites were identified by these two techniques: 6-keto-prostaglandin (PG)F1 alpha; 6-keto-PGE1; 2,3-dinor-6-keto-PGF 1 alpha; 2,3-dinor-13,14-dihydro-6,15-diketo-20-carboxyl PGF 1 alpha; and 2,3,18,19-tetranor-13,14-dihydro-6,15-diketo-20-carboxyl PGF 1 alpha. Several additional compounds, both polar and nonpolar in nature, which did not co-chromatograph with any of our standards were also detected. Early samples consisted predominantly of 6-keto-PGF 1 alpha and other 20-carbon metabolites. By 30 min, the predominant metabolites were the 16- and 18-carbon dicarboxylic acids. By 60 min, 85% of the radioactivity was associated with two unidentified polar compounds. The evidence suggests that 6-keto-PGF 1 alpha probably reflects only the transient levels of freshly entering PGI2 in the circulation, whereas levels of the most polar metabolites (e.g., dihydro-diketo-carboxyl tetranor-PGF 2 alpha) may be a better measure of the overall PGI2 presence due to its longer half-life in circulation

A comparison of oral misoprostol and vaginal prostaglandin e2 tablets for induction of labour at term

International Nuclear Information System (INIS)

Munzar, Z.

2015-01-01

To compare the efficacy and safety of oral misoprostol with prostaglandin E2 vaginal tablets for ripening of cervix and induction of labour at term. Study Design: A non blinded, randomised, controlled trial. Place and Duration of Study: Department of Obstetrics and Gynaecology, Pakistan Air Force Hospital, Air Headquarters Islamabad from July 2005 to January 2006. Patients and Methods: Hundred pregnant women with a singleton live pregnancy, at term (37-42 weeks) with cephalic presentation were selected for induction of labour for various indications having a Bishop's score of < or =5. These women were randomly allocated to receive either 100 micro gm of misoprostol rally repeated four hourly to a maximum of four doses or a 3mg PGE2 tablet vaginally repeated six hourly to a maximum of two doses. Main outcomes measured: Cervical score before and after oral misoprostol and prostaglandin E2 vaginal tablets, vaginal birth within 24 hours of first prostaglandin dose, no of patients having failed induction, caesarean sections (all), caesarean section for fetal distress and uterine hyperstimulation with associated changes in fetal heart rate. Results: Over the period of one year 100 women were recruited for the study, 50 to the misoprostol group and 50 to the vaginal prostaglandin E2 group. There was no significant differences between the two treatment groups in the primary outcomes: improvement in bishops score in both the groups, no of patients with failed induction in both the groups misoprostol 2/50 (4%) v PGE2 3/50 (6%) , vaginal birth achieved in 24 hours (misoprostol 27/50 (54%) v PGE2 29/50 (58%), caesarean sections 14/50 (28%) v 12/50(24%) caesarean section for fetal distress 4/50((8%) v 5/50(9%); uterine hyperstimulation with fetal heart rate changes 2/50 ((4%) v none in the PGE2 group.). Neonatal outcomes were not significantly different in the two groups. Conclusion: Oral misoprostol in strength of 100 micro gm has similar efficacy to vaginal PGE2 tablets

Prostaglandin E2 Levels of Aqueous and Vitreous Humor in Ketorolac 0.4% and Nepafenac 0.1% Administered Healthy Rabbits.

Science.gov (United States)

Acar, Ugur; Acar, Damla Erginturk; Tanriverdi, Cafer; Acar, Mutlu; Ozdemir, Ozdemir; Erikci, Acelya; Ornek, Firdevs

2017-06-01

To compare the lowering effects of ketorolac 0.4% and nepafenac 0.1% on aqueous and vitreous humor prostaglandin E 2 (PGE 2 ) levels in rabbits. Ketorolac and nepafenac ophthalmic solutions were administered to the right eyes of 24 healthy rabbits after randomized division into two groups. The left eyes of these rabbits were considered as controls for the two groups. On the 4th day of the experiment, the samples were taken from the aqueous and vitreous humors of the rabbits bilaterally, and PGE 2 levels were measured by an enzyme immune assay kit. Ketorolac and nepafenac achieved a statistically significant decrease (phumor (6.58 ± 4.62 and 9.83 ± 4.55 pg/mL, respectively). Both ketorolac and nepafenac inhibited PGE 2 levels in both the aqueous and vitreous humors of rabbits. Although PGE 2 -lowering effects were similar in the aqueous humor, nepafenac seemed to be more potent than ketorolac in the vitreous humor.

Migration in Vulnerable Deltas: A Research Strategy

Science.gov (United States)

Hutton, C.; Nicholls, R. J.; Allan, A.

2015-12-01

C. Hutton1, & R. J. Nicholls1, , 1 University of Southampton, University Road, Southampton, Hampshire, United Kingdom, SO17 1BJ. cwh@geodata. soton.ac.ukAbstractGlobally, deltas contain 500 million people and with rising sea levels often linked to large number of forced migrants are expected in the coming century. However, migration is already a major process in deltas, such as the growth of major cities such as Dhaka and Kolkata. Climate and environmental change interacts with a range of catchment and delta level drivers, which encompass a nexus of sea-level rise, storms, freshwater and sediment supply from the catchment, land degradation, subsidence, agricultural loss and socio-economic stresses. DECCMA (Deltas, Vulnerability and Climate Change: Migration and Adaptation/CARRIA) is investigating migration in the Ganges-Brahmaputra-Meghna (GBM), Mahanadi and Volta Deltas, including the influence of climate change. The research will explore migration from a range of perspectives including governance and stakeholder analysis, demographic analysis, household surveys of sending and receiving areas, macro-economic analysis, and hazards and hotspot analysis both historically and into the future. Migration under climate change will depend on other adaptation in the deltas and this will be examined. Collectively, integrated analysis will be developed to examine migration, other adaptation and development pathways with a particular focus on the implications for the poorest. This will require the development of input scenarios, including expert-derived exogenous scenarios (e.g., climate change) and endogenous scenarios of the delta developed in a participatory manner. This applied research will facilitate decision support methods for the development of deltas under climate change, with a focus on migration and other adaptation strategies.

INTELSAT III LIFTS OFF FROM LC 17A ABOARD A DELTA LAUNCH VEHICLE

Science.gov (United States)

1968-01-01

A Delta launch vehicle carrying the Intelsat III spacecraft was launched from Complex 17 at 8:09 p.m. EDT. A malfunction in flight resulted in the rocket breaking up some 102 seconds into the mission. Destruct action was initiated by the Air Force East Test Range some six seconds later when it was apparent that the mission could not succeed.

The prostaglandin EP1 receptor potentiates kainate receptor activation via a protein kinase C pathway and exacerbates status epilepticus

Science.gov (United States)

Rojas, Asheebo; Gueorguieva, Paoula; Lelutiu, Nadia; Quan, Yi; Shaw, Renee; Dingledine, Raymond

2014-01-01

Prostaglandin E2 (PGE2) regulates membrane excitability, synaptic transmission, plasticity, and neuronal survival. The consequences of PGE2 release following seizures has been the subject of much study. Here we demonstrate that the prostaglandin E2 receptor 1 (EP1, or Ptger1) modulates native kainate receptors, a family of ionotropic glutamate receptors widely expressed throughout the central nervous system. Global ablation of the EP1 gene in mice (EP1-KO) had no effect on seizure threshold after kainate injection but reduced the likelihood to enter status epilepticus. EP1-KO mice that did experience typical status epilepticus had reduced hippocampal neurodegeneration and a blunted inflammatory response. Further studies with native prostanoid and kainate receptors in cultured cortical neurons, as well as with recombinant prostanoid and kainate receptors expressed in Xenopus oocytes, demonstrated that EP1 receptor activation potentiates heteromeric but not homomeric kainate receptors via a second messenger cascade involving phospholipase C, calcium and protein kinase C. Three critical GluK5 C-terminal serines underlie the potentiation of the GluK2/GluK5 receptor by EP1 activation. Taken together, these results indicate that EP1 receptor activation during seizures, through a protein kinase C pathway, increases the probability of kainic acid induced status epilepticus, and independently promotes hippocampal neurodegeneration and a broad inflammatory response. PMID:24952362

Radiation-induced changes in production of prostaglandins Fsub(2α), E, and thromboxane B2 in guinea pig parenchymal lung tissues

International Nuclear Information System (INIS)

Steel, L.K.; Catravas, G.N.

1982-01-01

At 1 hour to 4 days after unilateral exposure of guinea pigs to a single dose (0.5, 1.5, or 3.0 Gy) of gamma-radiation, changes were detected in prostaglandin and thromboxane concentrations in parenchymal lung tissues. At 1-3 hours after exposure, tissue levels of PGFsub(2α), PGE, and thromboxane B 2 were significantly elevated in animals receiving 3.0 Gy, with the magnitude of alteration revealing a radiation dose effect. By 24 hours, tissue prostaglandin and thromboxane levels returned to near control values. Lung tissue synthesis of prostaglandins in response to H-1 receptor stimulation by the exogenous addition of histamine revealed similar radiation dose effects. The carboxylic acid ionophore A23187, exogenously applied to lung tissues, revealed a transient peak of increased sensitivity to ionophore stimulation for TxB 2 synthesis at 24 hours and for PGFsub(2α) at 72 hours post-irradiation. The data suggest that significant alterations in prostaglandin and thromboxane concentrations in parenchymal lung tissues occur following irradiation, in a dose-dependent manner, and that altered responsiveness to H-1 receptor stimulation and divalent cation transport also occur

Antagonizing Arachidonic Acid-Derived Eicosanoids Reduces Inflammatory Th17 and Th1 Cell-Mediated Inflammation and Colitis Severity

Directory of Open Access Journals (Sweden)

Jennifer M. Monk

2014-01-01

Full Text Available During colitis, activation of two inflammatory T cell subsets, Th17 and Th1 cells, promotes ongoing intestinal inflammatory responses. n-6 polyunsaturated fatty acid- (PUFA- derived eicosanoids, such as prostaglandin E2 (PGE2, promote Th17 cell-mediated inflammation, while n-3 PUFA antagonize both Th17 and Th1 cells and suppress PGE2 levels. We utilized two genetic mouse models, which differentially antagonize PGE2 levels, to examine the effect on Th17 cells and disease outcomes in trinitrobenzene sulfonic acid- (TNBS- induced colitis. Fat-1 mice contain the ω3 desaturase gene from C. elegans and synthesize n-3 PUFA de novo, thereby reducing the biosynthesis of n-6 PUFA-derived eicosanoids. In contrast, Fads1 Null mice contain a disrupted Δ5 desaturase gene and produce lower levels of n-6 PUFA-derived eicosanoids. Compared to Wt littermates, Fat-1 and Fads1 Null mice exhibited a similar colitic phenotype characterized by reduced colonic mucosal inflammatory eicosanoid levels and mRNA expression of Th17 cell markers (IL-17A, RORγτ, and IL-23, decreased percentages of Th17 cells and, improved colon injury scores (P≤0.05. Thus, during colitis, similar outcomes were obtained in two genetically distinct models, both of which antagonize PGE2 levels via different mechanisms. Our data highlight the critical impact of n-6 PUFA-derived eicosanoids in the promotion of Th17 cell-mediated colonic inflammation.

Reversal by prostaglandin E2 infusion of the effects of indomethacin on the excretion of nitrogenous compounds in the rat.

OpenAIRE

Rowe, D. J.; Gedeon, G.

1983-01-01

Rats were treated with Indomethacin (Indo; 2 mg/kg/d) with or without concomitant infusion of prostaglandin (PG)E2 (100 micrograms/d) to investigate the effects of inhibition of PG synthesis and PG replacement on the urinary excretion of total nitrogenous compounds, urea and creatinine and on the plasma concentration of urea and creatinine. The results indicated: (1) Indo significantly reduced the urine excretion of nitrogen, urea and creatinine within 48 hours of drug administration. (2) Thi...

Role of pathogen-derived cell wall carbohydrates and prostaglandin E2 in immune response and suppression of fish immunity by the oomycete Saprolegnia parasitica.

Science.gov (United States)

Belmonte, Rodrigo; Wang, Tiehui; Duncan, Gary J; Skaar, Ida; Mélida, Hugo; Bulone, Vincent; van West, Pieter; Secombes, Christopher J

2014-11-01

Saprolegnia parasitica is a freshwater oomycete that is capable of infecting several species of fin fish. Saprolegniosis, the disease caused by this microbe, has a substantial impact on Atlantic salmon aquaculture. No sustainable treatment against saprolegniosis is available, and little is known regarding the host response. In this study, we examined the immune response of Atlantic salmon to S. parasitica infection and to its cell wall carbohydrates. Saprolegnia triggers a strong inflammatory response in its host (i.e., induction of interleukin-1β1 [IL-1β1], IL-6, and tumor necrosis factor alpha), while severely suppressing the expression of genes associated with adaptive immunity in fish, through downregulation of T-helper cell cytokines, antigen presentation machinery, and immunoglobulins. Oomycete cell wall carbohydrates were recognized by fish leukocytes, triggering upregulation of genes involved in the inflammatory response, similar to what is observed during infection. Our data suggest that S. parasitica is capable of producing prostaglandin [corrected] E2 (PGE2) in vitro, a metabolite not previously shown to be produced by oomycetes, and two proteins with homology to vertebrate enzymes known to play a role in prostaglandin biosynthesis have been identified in the oomycete genome. Exogenous PGE2 was shown to increase the inflammatory response in fish leukocytes incubated with cell wall carbohydrates while suppressing genes involved in cellular immunity (gamma interferon [IFN-γ] and the IFN-γ-inducible protein [γ-IP]). Inhibition of S. parasitica zoospore germination and mycelial growth by two cyclooxygenase inhibitors (aspirin and indomethacin) also suggests that prostaglandins may be involved in oomycete development. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Radioimmunoassay determination of urinary prostaglandins in patients with progressive systemic sclerosis

International Nuclear Information System (INIS)

Ramirez P, P.; Erbessd, M.L.; Mares, G.; Recinos, G.; Graef S, A.; Lavalle, C.

1985-01-01

The results of urinary determinations of E-2 prostaglandines by radioimmunoassay (RIA) in 24-hour urine are presented for three groups: progressive systemic sclerotic patients with normotension and with elevated or normal APR, progressive systemic sclerotic patients with hypertension and with normal or low APR, control group of normal subjects. In a recent report of progressive systemic sclerosis in patients we demonstrated changes in the urine concentratrion of APR levels, sodium excretion and in total blood volume. Based on these findings we felt the need to perform quantifications of E-2 prostaglandines (PGE-2) in 24-hour recently taken urine samples stored at 70 0 and measure the sodium amounts excreted in the urine. We concluded that urinary determination of E-2 prostaglandines was the most suitable for our study as it allowed the establishment of relationships between APR, aldosterone and metabolic sodium balance. (author)

Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins[S

Science.gov (United States)

Subra, Caroline; Grand, David; Laulagnier, Karine; Stella, Alexandre; Lambeau, Gérard; Paillasse, Michael; De Medina, Philippe; Monsarrat, Bernard; Perret, Bertrand; Silvente-Poirot, Sandrine; Poirot, Marc; Record, Michel

2010-01-01

Exosomes are bioactive vesicles released from multivesicular bodies (MVB) by intact cells and participate in intercellular signaling. We investigated the presence of lipid-related proteins and bioactive lipids in RBL-2H3 exosomes. Besides a phospholipid scramblase and a fatty acid binding protein, the exosomes contained the whole set of phospholipases (A2, C, and D) together with interacting proteins such as aldolase A and Hsp 70. They also contained the phospholipase D (PLD) / phosphatidate phosphatase 1 (PAP1) pathway leading to the formation of diglycerides. RBL-2H3 exosomes also carried members of the three phospholipase A2 classes: the calcium-dependent cPLA2-IVA, the calcium-independent iPLA2-VIA, and the secreted sPLA2-IIA and V. Remarkably, almost all members of the Ras GTPase superfamily were present, and incubation of exosomes with GTPγS triggered activation of phospholipase A2 (PLA2)and PLD2. A large panel of free fatty acids, including arachidonic acid (AA) and derivatives such as prostaglandin E2 (PGE2) and 15-deoxy-Δ12,14-prostaglandinJ2 (15-d PGJ2), were detected. We observed that the exosomes were internalized by resting and activated RBL cells and that they accumulated in an endosomal compartment. Endosomal concentrations were in the micromolar range for prostaglandins; i.e., concentrations able to trigger prostaglandin-dependent biological responses. Therefore exosomes are carriers of GTP-activatable phospholipases and lipid mediators from cell to cell. PMID:20424270

Prostaglandin E2 Exerts Multiple Regulatory Actions on Human Obese Adipose Tissue Remodeling, Inflammation, Adaptive Thermogenesis and Lipolysis.

Directory of Open Access Journals (Sweden)

Verónica García-Alonso

Full Text Available Obesity induces white adipose tissue (WAT dysfunction characterized by unremitting inflammation and fibrosis, impaired adaptive thermogenesis and increased lipolysis. Prostaglandins (PGs are powerful lipid mediators that influence the homeostasis of several organs and tissues. The aim of the current study was to explore the regulatory actions of PGs in human omental WAT collected from obese patients undergoing laparoscopic bariatric surgery. In addition to adipocyte hypertrophy, obese WAT showed remarkable inflammation and total and pericellular fibrosis. In this tissue, a unique molecular signature characterized by altered expression of genes involved in inflammation, fibrosis and WAT browning was identified by microarray analysis. Targeted LC-MS/MS lipidomic analysis identified increased PGE2 levels in obese fat in the context of a remarkable COX-2 induction and in the absence of changes in the expression of terminal prostaglandin E synthases (i.e. mPGES-1, mPGES-2 and cPGES. IPA analysis established PGE2 as a common top regulator of the fibrogenic/inflammatory process present in this tissue. Exogenous addition of PGE2 significantly reduced the expression of fibrogenic genes in human WAT explants and significantly down-regulated Col1α1, Col1α2 and αSMA in differentiated 3T3 adipocytes exposed to TGF-β. In addition, PGE2 inhibited the expression of inflammatory genes (i.e. IL-6 and MCP-1 in WAT explants as well as in adipocytes challenged with LPS. PGE2 anti-inflammatory actions were confirmed by microarray analysis of human pre-adipocytes incubated with this prostanoid. Moreover, PGE2 induced expression of brown markers (UCP1 and PRDM16 in WAT and adipocytes, but not in pre-adipocytes, suggesting that PGE2 might induce the trans-differentiation of adipocytes towards beige/brite cells. Finally, PGE2 inhibited isoproterenol-induced adipocyte lipolysis. Taken together, these findings identify PGE2 as a regulator of the complex network of

17 CFR 240.15c3-1e - Deductions for market and credit risk for certain brokers or dealers (Appendix E to 17 CFR 240...

Science.gov (United States)

2010-04-01

... credit risk for certain brokers or dealers (Appendix E to 17 CFR 240.15c3-1). 240.15c3-1e Section 240....15c3-1(c)(2)(vi) and (c)(2)(vii) and to compute deductions for credit risk pursuant to this Appendix E... the broker or dealer will use to calculate deductions for market and credit risk on those categories...

Circadian and estral changes in the hypothalamic prostaglandin e content and [h]prostaglandin e binding in female rats.

Science.gov (United States)

Bommelaer-Bayet, M C; Wisner, A; Renard, C A; Levi, F A; Dray, F

1990-04-01

Abstract Prostaglandin E(2), (PGE(2)) is involved in the luteinizing hormone-releasing hormone-stimulated luteinizing hormone surge in female rats and may act via specific membrane receptors. The following studies were performed to determine whether there were any changes in the hypothalamic PGE(2) binding and/or PGE(2) content which were specific to proestrus and not to the rest of the estrous cycle. Groups of female Wistar rats were sacrificed at 3-h intervals throughout the estrous cycle to determine both the circadian and circaestral changes in the hypothalamic PGE(2) content and [(3)H]PGE(2) binding. The hypothalamic PGE(2) content was maximal at 1700 h on each of the 4 consecutive days of the estrous cycle but was independent of the stage of the cycle. [(3)H]PGE(2) binding also displayed a circadian rhythm; the lowest binding occurred near the circadian peak of PGE(2), suggesting that the PGE(2) binding sites were occupied by endogenous PGE(2). Since such circadian rhythms were not observed in the hypothalamus of male rats, they may be under the control of ovarian steroids. Also, since PGE(2) binding and the PGE(2) content both exhibit a diurnal pattern independent of the day of the cycle, there may be changes in the PGE(2) receptor-mediated process coupled to an adenylyl cyclase which could explain the luteinizing hormone surge in proestrus.

Intraocular pressure dynamics with prostaglandin analogs: a clinical application of water-drinking test

Directory of Open Access Journals (Sweden)

Özyol P

2016-07-01

Full Text Available Pelin Özyol,1 Erhan Özyol,1 Ercan Baldemir2 1Ophthalmology Department, 2Biostatistics Department, Faculty of Medicine, Mugla Sitki Kocman University, Mugla, Turkey Aim: To evaluate the clinical applicability of the water-drinking test in treatment-naive primary open-angle glaucoma patients. Methods: Twenty newly diagnosed primary open-angle glaucoma patients and 20 healthy controls were enrolled in this prospective study. The water-drinking test was performed at baseline and 6 weeks and 3 months after prostaglandin analog treatment. Peak and fluctuation of intraocular pressure (IOP measurements obtained with the water-drinking test during follow-up were analyzed. Analysis of variance for repeated measures and paired and unpaired t-tests were used for statistical analysis. Results: The mean baseline IOP values in patients with primary open-angle glaucoma were 25.1±4.6 mmHg before prostaglandin analog treatment, 19.8±3.7 mmHg at week 6, and 17.9±2.2 mmHg at month 3 after treatment. The difference in mean baseline IOP of the water-drinking tests was statistically significant (P<0.001. At 6 weeks of prostaglandin analog treatment, two patients had high peak and fluctuation of IOP measurements despite a reduction in baseline IOP. After modifying treatment, patients had lower peak and fluctuation of IOP values at month 3 of the study. Conclusion: Peak and fluctuation of IOP in response to the water-drinking test were lower with prostaglandin analogs compared with before medication. The water-drinking test can represent an additional benefit in the management of glaucoma patients, especially by detecting higher peak and fluctuation of IOP values despite a reduced mean IOP. Therefore, it could be helpful as a supplementary method in monitoring IOP in the clinical practice. Keywords: glaucoma, intraocular pressure, water-drinking test, prostaglandin analog, intra­ocular pressure fluctuation

The Value of Intravenous Prostaglandin E2 after Intra-uterine Death

African Journals Online (AJOL)

1974-09-21

Sep 21, 1974 ... using different routes of administration of the prosta- glandin. Given by ..... The disadvantages of intravenous prostaglandins are the systemic ... advantage of this method is that labour can be accurately monitored and the dose ...

Considerations on prevention of phlebitis and venous pain from intravenous prostaglandin E(1) administration by adjusting solution pH: in vitro manipulations affecting pH.

Science.gov (United States)

Kohno, Emiko; Nishikata, Mayumi; Okamura, Noboru; Matsuyama, Kenji

2008-01-01

Prostaglandin E(1) (PGE(1); Alprostadil Alfadex) is a potent vasodilator and inhibitor of platelet aggregation used to treat patients with peripheral vascular disease. The main adverse effects of intravenous PGE(1) administration, phlebitis and venous pain, arise from the unphysiologically low pH of infusion solutions. When PGE(1) infusion solutions with a pH value greater then 6 are used, phlebitis and venous pain are considered to be avoidable. Beginning with a PGE(1) infusion solution with pH greater than 6, we add the amount of 7% sodium bicarbonate needed to bring the solution to pH 7.4 if phlebitis or venous pain develops. In the present study we established a convenient nomogram showing the relationship between the titratable acidity of various infusion solutions and the volume of 7% sodium bicarbonate required to attain pH 7.4 for preventing the phlebitis and venous pain associated with PGE(1) infusion.

Aspirin inhibits interleukin 1-induced prostaglandin H synthase expression in cultured endothelial cells

International Nuclear Information System (INIS)

Wu, K.K.; Sanduja, R.; Tsai, A.L.; Ferhanoglu, B.; Loose-Mitchell, D.S.

1991-01-01

Prostaglandin H (PGH) synthase is a key enzyme in the biosynthesis of prostaglandins, thromboxane, and prostacyclin. In cultured human umbilical vein endothelial cells, interleukin 1 (IL-1) is known to induce the synthesis of this enzyme, thereby raising the level of PGH synthase protein severalfold over the basal level. Pretreatment with aspirin at low concentrations inhibited more than 60% of the enzyme mass and also the cyclooxygenase activity in IL-1-induced cells with only minimal effects on the basal level of the synthase enzyme in cells without IL-1. Sodium salicylate exhibited a similar inhibitory action whereas indomethacin had no apparent effect. Similarly low levels of aspirin inhibited the increased L-[ 35 S]methionine incorporation into PGH synthase that was induced by IL0-1 and also suppressed expression of the 2.7-kilobase PGH synthase mRNA. These results suggest that in cultured endothelial cells a potent inhibition of eicosanoid biosynthetic capacity can be effected by aspirin or salicylate at the level of PGH synthase gene expression. The aspirin effect may well be due to degradation of salicylate

Microsomal prostaglandin E synthase-1, ephrins, and ephrin kinases as suspected therapeutic targets in arthritis: exposed by "criminal profiling".

Science.gov (United States)

Romanovsky, Andrej A; Ivanov, Andrei I; Petersen, Scott R

2006-06-01

Feeding information obtained in one criminal case into the profile of another crime often helps to solve the latter. The literature on two different "crimes," namely, acute systemic inflammation and arthritis (including osteoarthritis [OA] and rheumatoid arthritis [RA] deals largely with the same "gang" of inflammatory mediators, such as prostaglandin (PG) E2. Early investigations suggested that microsomal PGE synthase-1 (mPGES-1; a terminal PGE2-synthesizing enzyme) plays a pivotal role in bacterial lipopolysaccharide (LPS)-induced systemic inflammation, but overlooked the possibility that the same enzyme could be involved in OA or RA. Later studies showed that mPGES-1 is indeed a key perpetrator in arthritic diseases, a fact that could have been predicted earlier by pooling the new knowledge about mPGES-1 into the profile of arthritic diseases. In this review, we analyze our recent study on the expression of erythropoietin-producing hepatocellular (Eph) receptor kinases and their ligands, ephrins, in LPS-induced systemic inflammation. By pooling these results together with literature data into the profile of RA, we conclude that Eph kinases and ephrins are prime suspects for being involved in the pathogenesis of RA. We further conjecture that the involvement of Eph kinases and ephrins may be realized via the induction of angiogenesis in the inflamed joint, promotion of leukocyte infiltration, and activation of the infiltrated cells. Studies to test this new hypothesis seem warranted, and our prediction is that the "smoking gun" will be found.

Modulation of enhanced vascular permeability by prostaglandins through alterations in blood flow (hyperemia). [/sup 85/Sr tracer technique

Energy Technology Data Exchange (ETDEWEB)

Johnston, M G; Hay, J B; Movat, H Z

1976-11-01

The enhanced vascular permeability induced by histamine or bradykinin in the skin of the guinea-pig and rabbit was significantly augmented by small amounts of prostaglandins of the E type. When injected alone these prostaglandins had little effect on vascular permeability. Furthermore, E type prostaglandins were found to be more potent at inducing hyperemia than either histamine or bradykinin. Prostaglandin F/sub 2/ alpha did not enhance the vascular permeability induced by histamine or bradykinin nor did it produce hyperemia in the skin. In the rat, prostaglandins alone enhanced vascular permeability but they also increased the effect of histamine, serotonin and bradykinin. Using /sup 85/Sr-microspheres to measure blood flow a correlation was found between the degree of hyperemia produced by prostaglandins and the degree to which they augmented enhanced vascular permeability due to histamine, serotonin or bradykinin. Prostaglandins therefore can directly mimic the hyperemia of the inflammatory process and can also modulate the changes in vascular permeability caused by other mediators of inflammation.

Effects of intraluteal implants of prostaglandin E1 or E2 on angiogenic growth factors in luteal tissue of Angus and Brahman cows.

Science.gov (United States)

Weems, Yoshie S; Ma, Yan; Ford, Stephen P; Nett, Terry M; Vann, Rhonda C; Lewis, Andrew W; Neuendorff, Don A; Welsh, Thomas H; Randel, Ronald D; Weems, Charles W

2014-12-01

Previously, it was reported that intraluteal implants containing prostaglandin E1 or E2 (PGE1 and PGE2) in Angus or Brahman cows prevented luteolysis by preventing loss of mRNA expression for luteal LH receptors and luteal unoccupied and occupied LH receptors. In addition, intraluteal implants containing PGE1 or PGE2 upregulated mRNA expression for FP prostanoid receptors and downregulated mRNA expression for EP2 and EP4 prostanoid receptors. Luteal weight during the estrous cycle of Brahman cows was reported to be lesser than that of Angus cows but not during pregnancy. The objective of this experiment was to determine whether intraluteal implants containing PGE1 or PGE2 alter vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), angiopoietin-1 (ANG-1), and angiopoietin-2 (ANG-2) protein in Brahman or Angus cows. On Day 13 of the estrous cycle, Angus cows received no intraluteal implant and corpora lutea were retrieved, or Angus and Brahman cows received intraluteal silastic implants containing vehicle, PGE1, or PGE2 on Day 13 and corpora lutea were retrieved on Day 19. Corpora lutea slices were analyzed for VEGF, FGF-2, ANG-1, and ANG-2 angiogenic proteins via Western blot. Day-13 Angus cow luteal tissue served as preluteolytic controls. Data for VEGF were not affected (P > 0.05) by day, breed, or treatment. PGE1 or PGE2 increased (P Angus cows compared with Day-13 and Day-19 Angus controls but decreased (P Angus controls. There was no effect (P > 0.05) of PGE1 or PGE2 on ANG-1 in Angus luteal tissue when compared with Day-13 or Day-19 controls, but ANG-1 was decreased (P Angus Vehicle controls when compared with Day-13 Angus controls, which was prevented (P Angus cows. There was no effect (P > 0.05) of PGE1 or PGE2 on ANG-2 in Brahman cows. PGE1 or PGE2 may alter cow luteal FGF-2, ANG-1, or ANG-2 but not VEGF to prevent luteolysis; however, species or breed differences may exist. Published by Elsevier Inc.

A biphasic response of urinary prostaglandin E2 excretion to water deprivation in conscious diabetes insipidus Brattleboro rats

DEFF Research Database (Denmark)

Kanters, J K; Holstein-Rathlou, N H; Christensen, P

1989-01-01

The effects of water deprivation on the urinary excretion rate of prostaglandin E2 (PGE2) were examined in conscious Brattleboro rats. In order to study the time course of the changes in the PGE2 excretory rate, urine was collected in 6 periods, Control: 0-1 hour (h.). 1: 3-4.5 h., 8-10 h., III: 12......-15 h., IV: 24-28 h. and V: 32-36 h. after removal of water and food. It was found that the PGE2 excretion rate changed in a biphasic pattern. During the first 2 experimental periods it increased. Thereafter it decreased towards the control value. There was an increase in PGE2 excretion with urinary...

Radiation-induced changes in production of prostaglandins Fsub(2. cap alpha. ), E, and thromboxane B/sub 2/ in guinea pig parenchymal lung tissues

Energy Technology Data Exchange (ETDEWEB)

Steel, L K; Catravas, G N [Armed Forces Radiobiology Research Inst., Bethesda, MD (USA)

1982-11-01

At 1 hour to 4 days after unilateral exposure of guinea pigs to a single dose (0.5, 1.5, or 3.0 Gy) of gamma-radiation, changes were detected in prostaglandin and thromboxane concentrations in parenchymal lung tissues. At 1-3 hours after exposure, tissue levels of PGFsub(2..cap alpha..), PGE, and thromboxane B/sub 2/ were significantly elevated in animals receiving 3.0 Gy, with the magnitude of alteration revealing a radiation dose effect. By 24 hours, tissue prostaglandin and thromboxane levels returned to near control values. Lung tissue synthesis of prostaglandins in response to H-1 receptor stimulation by the exogenous addition of histamine revealed similar radiation dose effects. The carboxylic acid ionophore A23187, exogenously applied to lung tissues, revealed a transient peak of increased sensitivity to ionophore stimulation for TxB/sub 2/ synthesis at 24 hours and for PGFsub(2..cap alpha..) at 72 hours post-irradiation. The data suggest that significant alterations in prostaglandin and thromboxane concentrations in parenchymal lung tissues occur following irradiation, in a dose-dependent manner, and that altered responsiveness to H-1 receptor stimulation and divalent cation transport also occur.

The Colorado river delta (Mexico: ecological importance and management = O delta do rio Colorado (Mexico: importância ecológica e gerenciamento

Directory of Open Access Journals (Sweden)

José Luis Fermán Almada

2008-10-01

Full Text Available The Colorado river delta is a unique coastal system in the world, as it combines two important systems: the Colorado river and the Gulf of California. Consequently, the delta is dominated by bilateral interests, and influenced by administrative, political and natural processes, which involve the countries of the United States and Mexico. Located in the northern part of the Gulf of California, under a condition of natural isolation, a series of environmental attributeshave been developed (biotic and abiotic that are only observed in is region. In this work, the development of the bilateral political relations and the most important ecological characteristicsare presented, as well as the management instruments that have been developed for over 80 years. From these issues, the possible scenario for the region is defined, and the development of methodologies for monitoring the effects of these possible tendencies on the natural components of the delta is proposed.O delta do rio Colorado é uma zona costeira única em todo o mundo, porassociar dois importantes sistemas: o próprio rio Colorado e o Golfo da Califórnia. Conseqüentemente, o delta é dominado por interesses bi-nacionais e influenciado por processos administrativos, políticos e naturais, envolvendo os Estados Unidos e o México. Localizado no norte do Golfo da Califórnia, sob uma condição de isolamento natural,desenvolveu-se uma série de atributos ambientais (bióticos e abióticos que só podem ser vistos nessa região. Neste trabalho, são apresentados o desenvolvimento das relações políticas bilaterais e as características ecológicas mais importantes, bem como osmecanismos de gerenciamento que vêm sido desenvolvidos por mais de 80 anos. A partir dessas questões, é definido um cenário tendencial possível para a região, e o desenvolvimento de metodologias para o acompanhamento dos efeitos dessas possíveis tendências sobre os componentes naturais do delta é proposto.

Intracrine prostaglandin E2 pro-tumoral actions in prostate epithelial cells originate from non-canonical pathways.

Science.gov (United States)

Madrigal-Martínez, Antonio; Fernández-Martínez, Ana B; Lucio Cazaña, Francisco J

2018-04-01

Prostaglandin E 2 (PGE 2 ) increases cell proliferation and stimulates migratory and angiogenic abilities in prostate cancer cells. However, the effects of PGE 2 on non-transformed prostate epithelial cells are unknown, despite the fact that PGE 2 overproduction has been found in benign hyperplastic prostates. In the present work we studied the effects of PGE 2 in immortalized, non-malignant prostate epithelial RWPE-1 cells and found that PGE 2 increased cell proliferation, cell migration, and production of vascular endothelial growth factor-A, and activated in vitro angiogenesis. These actions involved a non-canonic intracrine mechanism in which the actual effector was intracellular PGE 2 (iPGE 2 ) instead of extracellular PGE 2 : inhibition of the prostaglandin uptake transporter (PGT) or antagonism of EP receptors prevented the effects of PGE 2 , which indicated that PGE 2 activity depended on its carrier-mediated translocation from the outside to the inside of cells and that EP receptors located intracellularly (iEP) mediated the effects of PGE 2 . iPGE 2 acted through transactivation of epidermal growth factor-receptor (EGFR) by iEP, leading to increased expression and activity of hypoxia-inducible factor-1α (HIF-1α). Interestingly, iPGE 2 also mediates the effects of PGE 2 on prostate cancer PC3 cells through the axis iPGE 2 -iEP receptors-EGFR-HIF-1α. Thus, this axis might be responsible for the growth-stimulating effects of PGE 2 on prostate epithelial cells, thereby contributing to prostate proliferative diseases associated with chronic inflammation. Since this PGT-dependent non-canonic intracrine mechanism of PGE 2 action operates in both benign and malignant prostate epithelial cells, PGT inhibitors should be tested as a novel therapeutic modality to treat prostate proliferative disease. © 2017 Wiley Periodicals, Inc.

Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons

Energy Technology Data Exchange (ETDEWEB)

Kim, Sojin; Jin, Zhenhua; Lee, Goeun [Department of Physiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Park, Yong Seek; Park, Cheung-Seog [Department of Microbiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Jin, Young-Ho, E-mail: jinyh@khu.ac.kr [Department of Physiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of)

2015-01-02

Highlights: • Prostaglandin E2 (PGE{sub 2}) effect was tested on visceral afferent neurons. • PGE{sub 2} did not evoke response but potentiated serotonin (5-HT) currents up to 167%. • PGE{sub 2}-induced potentiation was blocked by E-prostanoid type 4 receptors antagonist. • PGE{sub 2} effect on 5-HT response was also blocked by protein kinase A inhibitor KT5720. • Thus, PGE{sub 2} modulate visceral afferent neurons via synergistic signaling with 5-HT. - Abstract: Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E{sub 2} (PGE{sub 2}) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE{sub 2} induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE{sub 2} effect on visceral afferent sensory neurons of the rat. Interestingly, PGE{sub 2} itself did not evoked any response but enhanced serotonin (5-HT)-evoked currents up to 167% of the control level. The augmented 5-HT responses were completely inhibited by a 5-HT type 3 receptor antagonist, ondansetron. The PGE{sub 2}-induced potentiation were blocked by a selective E-prostanoid type4 (EP{sub 4}) receptors antagonist, L-161,982, but type1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE{sub 2} effects. PGE{sub 2} induced 5-HT current augmentation was observed on 15% and 21% of the stomach and ileum projecting neurons, respectively. Current results suggest a synergistic signaling in visceral afferent neurons underlying gastrointestinal disorder involving PGE{sub 2} potentiation of 5-HT currents. Our findings may open a possibility for screen a new type drugs with lower side effects than currently using steroidal prostaglandin

N-Acetylcysteine enhances the action of anti-inflammatory drugs as suppressors of prostaglandin production in monocytes

Directory of Open Access Journals (Sweden)

Erica Hoffer

2002-01-01

Full Text Available The anti-inflammatory effect of non-steroidal anti-inflammatory drugs (NSAIDs is associated with inhibition of cyclooxygenase (COX, the rate-limiting enzyme responsible for the synthesis of prostaglandins. Since oxygen free radicals can act as second cellular messengers, especially to modulate the metabolism of arachidonic acid and the prostaglandin tract, it seems plausible that antioxidants might affect the production of prostaglandin by activated cells. This research is focused on the effect of the antioxidant N-acetylcysteine (NAC on the inhibition of prostaglandin E2 formation in activated monocytes by specific and non-specific COX inhibitors. We found that lipopolysaccharide-induced prostaglandin E2 formation was significantly reduced by rofecoxib and by diclofenac, two NSAIDs. Addition of NAC to each of these drugs enhanced the effect of the NSAIDs. These results suggest that one might expect either a potentiation of the anti-inflammatory effect of COX inhibitors by their simultaneous administration with NAC, or obtaining the same anti-inflammatory at lower drug levels.

Do prostaglandins affect cellular radiosensitivity in vitro

International Nuclear Information System (INIS)

Millar, B.C.; Jinks, S.

1984-01-01

The authors were unable to detect any change in the in vitro radiation response of mouse fibrosarcoma cells, HSDM 1 C 1 , which secrete 2 μg PGE 2 /mg cell protein/24 h, in the presence of the prostaglandin biosynthesis inhibitor flurbiprofen. Furthermore, addition of exogenous PGE 1 or PGA 2 to cultures of Chinese hamster cells was similarly without effect on radiation response. Although a high concentration of PGA 2 inhibited the growth of Chinese hamster cells in vitro this effect disappeared upon removal of the prostaglandin. The implications of these results for radiotherapy are discussed. (author)

Dependence of {delta}E effect on internal stresses in nickel: Experimental results by laser interferometry

Energy Technology Data Exchange (ETDEWEB)

Chicharro, J.M. [Dept. de Mecanica Aplicada e Ingenieria de Proyectos, E.T.S.I. Industriales, Universidad de Castilla-La Mancha, Avd. Camilo Jose Cela s/n, 13071 Ciudad Real (Spain)]. E-mail: josemanuel.chicharro@uclm.es; Bayon, A. [Dept. de Fisica Aplicada a los Recursos Naturales, E.T.S.I. Minas, Universidad Politecnica de Madrid, c/Rios Rosas, 21, 28003 Madrid (Spain); Salazar, F. [Dept. de Fisica Aplicada a los Recursos Naturales, E.T.S.I. Minas, Universidad Politecnica de Madrid, c/Rios Rosas, 21, 28003 Madrid (Spain)

2006-02-15

The speckle heterodyne interferometry is applied to the study of the dependence of Young's modulus on both the magnetic field and the internal stresses in a soft ferromagnetic material. Young's modulus is determined from the first natural longitudinal frequency of a slender magnetic rod positioned within a solenoid. Vibration of the sample is detected by an optical heterodyne system with a wide bandwidth. The samples are heated to above the Curie point and then cooled at several rates in order to induce different internal stresses. The study refers to nickel rods 10mm in diameter and 110mm in length. The grain sizes of the samples are also determined and related to changes in {delta}E.

Angiotensin II potentiates prostaglandin stimulation of cyclic AMP levels in intact bovine adrenal medulla cells but not adenylate cyclase in permeabilized cells.

Science.gov (United States)

Boarder, M R; Plevin, R; Marriott, D B

1988-10-25

The level of cyclic AMP in primary cultures of bovine adrenal medulla cells is elevated by prostaglandin E1. Angiotensin II is commonly reported to act on receptors linked to phosphoinositide metabolism or to inhibition of adenylate cyclase. We have investigated the effect of angiotensin II on prostaglandin E1-stimulated cyclic AMP levels in these primary cultures. Rather than reducing cyclic AMP levels, we have found that angiotensin II powerfully potentiates prostaglandin E1-stimulated cyclic AMP accumulation in intact cells, both in the presence and absence of phosphodiesterase inhibitors. The 50% maximal response was similar to that for stimulation of phosphoinositide breakdown by angiotensin II in these cultures. The potentiation of stimulated cyclic AMP levels was seen, although to a smaller maximum, with the protein kinase C (Ca2+/phospholipid-dependent enzyme) activating phorbol ester tetradecanoyl phorbolacetate and with the synthetic diacylglycerol 1-oleoyl-2-acetylglycerol; pretreatment (24 h) with active phorbol ester, which would be expected to diminish protein kinase C levels, attenuated the angiotensin II potentiation of cyclic AMP. Using digitonin-permeabilized cells we showed that adenylate cyclase activity was stimulated by prostaglandin E1 with the same dose-response relationship as was cyclic AMP accumulation in intact cells, but the permeabilized cells showed no response to angiotensin II. The results are discussed with respect to the hypothesis that the angiotensin II influence on cyclic AMP levels is mediated, in part, by diacylglycerol stimulation of protein kinase C.

In vitro anti-inflammatory activity of carvacrol: Inhibitory effect on COX-2 catalyzed prostaglandin E-2 biosynthesis

Czech Academy of Sciences Publication Activity Database

Landa, Přemysl; Kokoška, L.; Přibylová, Marie; Vaněk, Tomáš; Maršík, Petr

2009-01-01

Roč. 32, č. 1 (2009), s. 75-78 ISSN 0253-6269 R&D Projects: GA ČR GA525/08/1179; GA MŠk 1P04OC926.001 Institutional research plan: CEZ:AV0Z50380511 Keywords : Carvacrol * Cyclooxygenase * Prostaglandin Subject RIV: GM - Food Processing Impact factor: 1.159, year: 2009

Increased jejunal prostaglandin E2 concentrations in patients with acute cholera

NARCIS (Netherlands)

Speelman, P.; Rabbani, G. H.; Bukhave, K.; Rask-Madsen, J.

1985-01-01

Supraphysiologic doses of prostaglandins (PGs) mimic the effect of cholera toxin and cAMP in the small intestine, but not all observations are explicable in terms of the theory that links PGs to cAMP. Because no data exist on endogenous PGs in human cholera we measured PGE2 concentrations in jejunal

Prostaglandin E2 stimulates the expression of cumulus expansion-related genes in pigs: the role of protein kinase B

Czech Academy of Sciences Publication Activity Database

Blaha, Milan; Procházka, Radek; Adámková, K.; Nevoral, J.; Němcová, Lucie

2017-01-01

Roč. 130, č. 2 (2017), s. 38-46 ISSN 1098-8823 R&D Projects: GA MZe(CZ) QJ1510138; GA MŠk EF15_003/0000460 Institutional support: RVO:67985904 Keywords : cumulus * oocyte * prostaglandin E2 * protein kinase B Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Reproductive biology (medical aspects to be 3) Impact factor: 2.640, year: 2016

Do prostaglandins affect cellular radiosensitivity in vitro

Energy Technology Data Exchange (ETDEWEB)

Millar, B.C.; Jinks, S. (Institute of Cancer Research, Sutton (UK). Surrey Branch)

1984-10-01

The authors were unable to detect any change in the in vitro radiation response of mouse fibrosarcoma cells, HSDM/sub 1/C/sub 1/, which secrete 2 ..mu..g PGE/sub 2//mg cell protein/24 h, in the presence of the prostaglandin biosynthesis inhibitor flurbiprofen. Furthermore, addition of exogenous PGE/sub 1/ or PGA/sub 2/ to cultures of Chinese hamster cells was similarly without effect on radiation response. Although a high concentration of PGA/sub 2/ inhibited the growth of Chinese hamster cells in vitro this effect disappeared upon removal of the prostaglandin. The implications of these results for radiotherapy are discussed.

15-Deoxy-{Delta}{sup 12,14}-prostaglandin J{sub 2} impairs the functions of histone acetyltransferases through their insolubilization in cells

Energy Technology Data Exchange (ETDEWEB)

Hironaka, Asako [Department of Biochemistry, Nara Medical University, Shijo-Cho 840, Kashihara, Nara 634-8521 (Japan); Morisugi, Toshiaki; Kawakami, Tetsuji [Department of Oral and Maxillofacial Surgery, Nara Medical University, Shijo-Cho 840, Kashihara, Nara 634-8521 (Japan); Miyagi, Ikuko [Laboratory of Biometabolic Chemistry, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-Cho, Okinawa 903-0215 (Japan); Tanaka, Yasuharu, E-mail: yatanaka@med.u-ryukyu.ac.jp [Laboratory of Biometabolic Chemistry, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-Cho, Okinawa 903-0215 (Japan)

2009-12-11

The cyclopentenonic prostaglandin 15-deoxy-{Delta}{sup 12,14}-PG J{sub 2} (15d-PGJ{sub 2}) is a metabolite derived from PGD{sub 2}. Although 15d-PGJ{sub 2} has been demonstrated to be a potent ligand for peroxisome proliferator activated receptor {gamma} (PPAR{gamma}), the functions are not fully understood. In order to examine the effect of 15d-PGJ{sub 2} on histone acetyltransferases (HATs), several lines of cell including mouse embryonic fibroblast (MEF) cells were exposed to 15d-PGJ{sub 2}. Three types of HAT, p300, CREB-binding protein (CBP), and p300/CBP-associated factor (PCAF), selectively disappeared from the soluble fraction in time- and dose-dependent manners. Inversely, HATs in the insoluble fraction increased, suggesting their conformational changes. The decrease in the soluble form of HATs resulted in the attenuation of NF-{kappa}B-, p53-, and heat shock factor-dependent reporter gene expressions, implying that the insoluble HATs are inactive. The resultant insoluble PCAF and p300 seemed to be digested by proteasome, because proteasome inhibitors caused the accumulation of insoluble HATs. Taken together, these results indicate that 15d-PGJ{sub 2} attenuates some gene expressions that require HATs. This inhibitory action of 15d-PGJ{sub 2} on the function of HATs was independent of PPAR{gamma}, because PPAR{gamma} agonists could not mimick 15d-PGJ{sub 2} and PPAR{gamma} antagonists did not inhibit 15d-PGJ{sub 2}.

Cerebral correlates of delta waves during non-REM sleep revisited.

Science.gov (United States)

Dang-Vu, Thien Thanh; Desseilles, Martin; Laureys, Steven; Degueldre, Christian; Perrin, Fabien; Phillips, Christophe; Maquet, Pierre; Peigneux, Philippe

2005-10-15

We aimed at characterizing the neural correlates of delta activity during Non Rapid Eye Movement (NREM) sleep in non-sleep-deprived normal young adults, based on the statistical analysis of a positron emission tomography (PET) sleep data set. One hundred fifteen PET scans were obtained using H(2)(15)O under continuous polygraphic monitoring during stages 2-4 of NREM sleep. Correlations between regional cerebral blood flow (rCBF) and delta power (1.5-4 Hz) spectral density were analyzed using statistical parametric mapping (SPM2). Delta power values obtained at central scalp locations negatively correlated during NREM sleep with rCBF in the ventromedial prefrontal cortex, the basal forebrain, the striatum, the anterior insula, and the precuneus. These regions embrace the set of brain areas in which rCBF decreases during slow wave sleep (SWS) as compared to Rapid Eye Movement (REM) sleep and wakefulness (Maquet, P., Degueldre, C., Delfiore, G., Aerts, J., Peters, J.M., Luxen, A., Franck, G., 1997. Functional neuroanatomy of human slow wave sleep. J. Neurosci. 17, 2807-S2812), supporting the notion that delta activity is a valuable prominent feature of NREM sleep. A strong association was observed between rCBF in the ventromedial prefrontal regions and delta power, in agreement with electrophysiological studies. In contrast to the results of a previous PET study investigating the brain correlates of delta activity (Hofle, N., Paus, T., Reutens, D., Fiset, P., Gotman, J., Evans, A.C., Jones, B.E., 1997. Regional cerebral blood flow changes as a function of delta and spindle activity during slow wave sleep in humans. J. Neurosci. 17, 4800-4808), in which waking scans were mixed with NREM sleep scans, no correlation was found with thalamus activity. This latter result stresses the importance of an extra-thalamic delta rhythm among the synchronous NREM sleep oscillations. Consequently, this rCBF distribution might preferentially reflect a particular modulation of the

Putative role of prostaglandin receptor in intracerebral hemorrhage

Directory of Open Access Journals (Sweden)

Shekher eMohan

2012-10-01

Full Text Available Each year, approximately 795,000 people experience a new or recurrent stroke. Of all strokes, 84% are ischemic, 13% are intracerebral hemorrhage (ICH strokes and 3% are subarachnoid hemorrhage (SAH strokes. Despite the decreased incidence of ischemic stroke, there has been no change in the incidence of hemorrhagic stroke in the last decade. ICH is a devastating disease 37-38% of patients between the ages of 45-64 die within 30 days. In an effort to prevent ischemic and hemorrhagic strokes we and others have been studying the role of prostaglandins and their receptors. Prostaglandins are bioactive lipids derived from the metabolism of arachidonic acid. They sustain homeostatic functions and mediate pathogenic mechanisms, including the inflammatory response. Most prostaglandins are produced from specific enzymes and act upon cells via distinct G-protein coupled receptors. The presence of multiple prostaglandin receptor’s cross-reactivity and coupling to different signal transduction pathways allow differentiated cells to respond to prostaglandins in a unique manner. Due to the number of prostaglandin receptors, prostaglandin-dependent signaling can function either to promote neuronal survival or injury following acute excitotoxicity, hypoxia, and stress induced by ICH. To better understand the mechanisms of neuronal survival and neurotoxicity mediated by prostaglandin receptors, it is essential to understand downstream signaling. Several groups including ours have discovered unique roles for prostaglandin receptors in rodent models of ischemic stroke, excitotoxicity, and Alzheimer disease, highlighting the emerging role of prostaglandin receptor signaling in hemorrhagic stroke with a focus on cyclic-adenosine monophosphate (cAMP and calcium (Ca2+ signaling. We review current ICH data and discuss future directions notably on prostaglandin receptors, which may lead to the development of unique therapeutic targets against hemorrhagic stroke and

[Ocular Surface Evaluation in Patients Treated with Prostaglandin Analogues Considering Preservative Agent].

Science.gov (United States)

Mlčáková, E; Mlčák, P; Karhanová, M; Langová, K; Marešová, K

The aim of this study was to evaluate the ocular surface in patients treated with prostaglandin analogues considering contained preservative agent. 60 patients with glaucoma or ocular hypertension treated with prostaglandin analogue monotherapy were enrolled in this observational study. 20 patients with glaucoma suspect or ocular hypertension without local or systemic glaucoma medication formed the control group. Demographic data and medical history were recorded for each participant. Patients filled in the Ocular surface disease index© (OSDI) questionnaire and underwent an ophthalmological examination including assessment of conjunctival hyperaemia according to Efron, tear film break up time (BUT) and fluorescein staining according to the Oxford grading scheme. Treated participants were divided into 3 groups according to the preservative contained in the currently used prostaglandin analogue: the preservative-free group (18 patients), the polyquaternium group (17 patients) and the benzalkonium chloride (BAK) group (25 patients). The control group had significantly lower fluorescein staining than the preservative-free group (p=0.001), the polyquaternium group (p=0.007) and the BAK group (p=0.002). The conjunctival hyperaemia was significantly lower in the preservative-free group compared to the polyquaternium group (p=0.011). There was no significant difference among the other groups. The difference neither in the OSDI score nor in the BUT was statistically important. This study confirmed that the ocular surface is worse in patients treated with prostaglandin analogue monotherapy than in people without glaucoma medication. A significant difference among treated patients depending on a preservative agent was not proved.Key words: benzalkonium chloride, glaucoma, ocular surface disease, preservatives, prostaglandin analogues.

Perubahan Kadar Prostaglandin E2 (PGE2) Setelah Aplikasi Ekstrak Gambir (Uncaria Gambir ROXB) Pada Kasus Pulpitis Ireversible.

OpenAIRE

Samad, Rasmidar

2017-01-01

The dental pulp was soft tissue, reside in the cental of tooth, enclosed by, email, dentine and cementum, Inflammation of dental pulp was called pulpitis. Two groups of pulpitis, among these pulpitis, irreversible pulpitis. Design of this researc pre and post test to evaluate change the levels of prostaglandin E2 (PGE2) post application gambier (Uncaria Gambier Roxb) extract, in January-April 2016 in the Biofarmaca Laboratory Research Center Activities Faclty of Pharmacy.

Observations of the D, E and delta mesons in π-p interactions at 12 and 15 GeV/c

International Nuclear Information System (INIS)

Corden, M.J.; Dowell, J.D.; Garvey, J.

1978-07-01

The D(1285), E(1420) and delta(975) mesons produced in 12 and 15 GeV/c π - p interactions at the CERN Omega Spectrometer have been observed. Production cross sections and decay branching ratios are presented. Analysis of the decay D(1285) → delta(975) π favours a spin parity assignment of 1 + . (author)

FATTY ACID COMPOSITION AND PROSTAGLANDIN CONTENT OF THE RED SEAWEED Gracilaria sp. FROM INDONESIA

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Muhammad Ikbal Illijas

2012-06-01

Full Text Available High content of polyunsaturated fatty acids (PUFAs such as arachidonic and eicosapentaenoic acids are typical for the red alga. Analysis of fatty acid composition and prostaglandin content was conducted in the red alga Gracilaria sp. from Indonesia. Total lipid of the alga was extracted with CHCl3-MeOH (2:1, v/v. Analysis of the fatty acids composition was performed on gas chromatography (GC equipped with omega wax column (30 m x 0,32 mm i.d., Supelco, PA, USA and analysis of prostaglandins were carried out by HPLC on ODS column (Mightysil RP-18 GP, 250 mm x 4.6 mm, 5 μm. The content of fatty acids high for were palmitic acid (50% and arachidonic acid (26.9%, whereas prostaglandin E2 was identified and found lower concentration (44.2 μg/gram total lipid.

Benthic sediment data from eleven stations in the Mobile-Tensaw River Delta, Alabama on 17 June 1981 (NODC Accession 0118497)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Benthic sediment samples were collected from eleven stations in the Mobile-Tensaw River Delta on 17 June 1981. Samples were analyzed for particle size distribution...

Chloroquine, quinine, procaine, quinidine and clomipramine are prostaglandin agonists and antagonists.

Science.gov (United States)

Manku, M S; Horrobin, D F

1976-11-01

Chloroquine, quinine, procaine, quinidine and clomipramine behave as prostaglandin (PG) antagonists in a rat mesenteric vascular bed preparation. The ID50 concentrations were within the range of therapeutically effective human plasma levels in each case. Antagonism to PGE2 was studied in detail and seemed to be at least in part competitive. The drugs also antagonized the effects of PGs A1, A2, F2alpha and E1. Each drug also had weak prostaglandin agonist activity but only over a very narrow range of concentrations. It is possible that some of the clinical actions of these drugs may depend on blockade or imitation of natural PG effects. The findings suggest new approaches to the search for PG antagonists, a new screening technique for anti-inflammatory drugs and possible new uses for these established drugs. A preliminary study suggests that chloroquine may be successful in closing a patent ductus arteriosus in infants.

Observation of the D, E and delta mesons in π-p interactions at 12 and 15 GeV/c

International Nuclear Information System (INIS)

Corden, M.J.; Dowell, J.D.; Garvey, J.; Jobes, M.; Kenyon, I.R.; Mawson, J.; McMahon, T.J.; Corbett, I.F.; Esterling, R.J.; Lipman, N.H.; Litchfield, P.J.; Sumorok, K.C.T.O.; Bellamy, E.H.; Green, M.G.; Harnew, N.; Lister, J.B.; Lister, J.R.; Robertson, A.W.; Stacey, B.J.; Strong, J.A.; Thomas, D.H.

1978-01-01

The authors have observed the D(1285), E(1420) and delta(975) mesons produced in 12 and 15 GeV/c π - p interactions at the CERN Omega Spectrometer. Production cross sections and decay branching ratios are presented. Analysis of the decay D(1285)→delta(975)π favours a spin-parity assignment of 1 + . (Auth.)

Tartrazine and the prostaglandin system.

Science.gov (United States)

Gerber, J G; Payne, N A; Oelz, O; Nies, A S; Oates, J A

1979-04-01

The effect of tartrazine on prostaglandin production was evaluated in several in vitro systems in order to elucidate the interrelationship between aspirin-sensitive asthma and tartrazine. Unlike the nonsteroidal anti-inflammatory drugs, tartrazine did not inhibit cyclooxygenase activity in sheep seminal vesicles, guinea pig lung microsomes, and human platelets. Tartrazine had no effect on the activation of acyl hydrolase, which is the rate-limiting step in prostaglandin production. The major metabolite of tartrazine, sulfanilic acid, also had no inhibitory effect on the sheep seminal vesicle cyclooxygenase. In view of these findings, if there is a cross-sensitivity between tartrazine and aspirin in aspirin-sensitive asthmatics, it is unlikely to be on the basis of prostaglandin inhibition.

Interaction of 3,8-diazabicyclo (3.2.1) octanes with mu and delta opioid receptors.

Science.gov (United States)

Cignarella, G; Barlocco, D; Tranquillini, M E; Volterra, A; Brunello, N; Racagni, G

1988-05-01

A series of 3,8-diazabicyclo (3.2.1) octanes (DBO) (1) substituted at the nitrogen atoms by acyl and aralkenyl groups, were tested in in vitro binding assays towards mu and delta opioid receptors. The most representative terms (1a, 1d, 1g, 1j,) were also evaluated for the analgesic potency in vivo by the hot plate method. Among the compounds tested the most potent was the p.nitrocinnamyl DBO (1d) which displayed a mu/delta selectivity and an analgesic activity respectively 25 and 17 fold those of morphine. On the contrary, the m.hydroxycinnamyl DBO (1g) was markedly less active as agonist than the parent 1a, thus suggesting that structure 1 interacts with opioid receptors in a different fashion than morphine. Compound 1j isomer of 1a which is provided with high mu affinity, but lower analgesic potency, was found to possess a mixed agonist-antagonist activity.

Regulation of cyclic AMP metabolism by prostaglandins in rabbit cortical collecting tubule cells

International Nuclear Information System (INIS)

Sonnenburg, W.K.

1987-01-01

In the rabbit cortical collecting tubule (RCCT), prostaglandin E 1 (PGE 1 ) and prostaglandin E 2 (PGE 2 ) at 1 nM inhibit arginine-vasopressin (AVP)-induced water reabsorption, while 100 nM PGE 1 and PGE 2 alone stimulate water reabsorption. Reported here are studies designed to investigate the molecular basis for the biphasic physiological action of PGE 1 and PGE 2 in the collecting duct. In freshly isolated RCCT cells, PGE 1 , PGE 2 , and 16,16-dimethyl-PGE 2 (DM-PGE 2 ) stimulated cAMP synthesis at concentrations ranging from 0.1 to 10 M. Other prostaglandins including the synthetic PGE 2 analogue, sulprostone, failed to stimulate cAMP synthesis. Moreover, sulprostone did not antagonize PGE 2 -stimulated cAMP formation. In contrast, PGE 2 and sulprostone at concentrations ranging from 1 to 100 nM, inhibited AVP-induced cAMP accumulation in freshly isolated RCCT cells. PGE 2 , PGE 1 , DM-PGE 2 and sulprostone at 100 nM were equally effective in inhibiting AVP-induced cAMP formation. Moreover sulprostone inhibited AVP-stimulated adenylate cyclase activity. These results suggest that PGE derivatives mediate either inhibition or activation of adenylate cyclase by stimulating different PGE receptors. To further test this concept, PGE 2 binding to freshly isolated RCCT cell membranes was characterized. Two different classes of PGE 2 binding were detected. / 3 H/PGE 2 binding to the high affinity class of sites was increased by the GTP-analogue, GTP S, while pertussis toxin pretreatment blocked the stimulatory action. In contrast, / 3 H/ PGE 2 binding to the low affinity class of sites was decreased by GTP S; this inhibitory effect was not blocked by pertussis toxin pretreatment

Effects of endogenous pyrogen and prostaglandin E2 on hypothalamic neurons in rat brain slices.

Science.gov (United States)

Watanabe, T; Morimoto, A; Murakami, N

1987-06-01

We investigated the effects of endogenous pyrogen and prostaglandin E2 (PGE2) on the preoptic and anterior hypothalamic (POAH) neurons using brain slice preparations from the rat. Partially purified endogenous pyrogen did not change the activities of most of the neurons in the POAH region when applied locally through a micropipette attached to the recording electrode in proximity to the neurons. This indicates that partially purified endogenous pyrogen does not act directly on the neuronal activity in the POAH region. The partially purified endogenous pyrogen, applied into a culture chamber containing a brain slice, facilitated the activities in 24% of the total neurons tested, regardless of the thermal specificity of the neurons. Moreover, PGE2 added to the culture chamber facilitated 48% of the warm-responsive, 33% of the cold-responsive, and 29% of the thermally insensitive neurons. The direction of change in neuronal activity induced by partially purified endogenous pyrogen appears to be almost the same as that induced by PGE2 when these substances were applied by perfusion to the same neuron in the culture chamber. These results suggest that partially purified pyrogen applied to the perfusate of the culture chamber stimulates some constituents of brain tissue to synthesize and release prostaglandin, which in turn affects the neuronal activity of the POAH region.

In Vivo Anti-inflammatory Activity of Lipoic Acid Derivatives in Mice 

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Brunon Kwiecień

2013-04-01

Full Text Available Background: In mammals lipoic acid (LA and its reduced form dihydrolipoic acid (DHLA function as cofactors for multienzymatic complexes catalyzing the decarboxylation of α-ketoacids. Moreover, LA is used as a drug in a variety of diseases including inflammatory diseases. The aim of the study was to examine anti-inflammatory properties of LA metabolites.Material/methods:The present paper reports the chemical synthesis of 2,4-bismethylthio-butanoic acid (BMTBA and tetranor-dihydrolipoic acid (tetranor-DHLA. BMTBA is one of the biotransformation products of LA, while tetranor-DHLA is an analogue of DHLA. Structural identity of these compounds was confirmed by 1H NMR. These compounds were assessed for their anti-inflammatory activity in mice. For this purpose, the zymosan-induced peritonitis and the carrageenan-induced hind paw edema animal models were applied.Results/conclusions: The obtained results indicated that the early vascular permeability measured at 30 min of zymosan-induced peritonitis was significantly inhibited in groups receiving BMTBA (10, 30, 50 mg/kg. The early infiltration of neutrophils measured at 4 hours of zymosan-induced peritonitis was inhibited in the group receiving BMTBA (50 mg/kg and tetranor-DHLA (50 mg/kg. The results indicated that the increase in paw edema was significantly inhibited in the groups receiving BMTBA (50, 100 mg/kg and tetranor-DHLA (30, 50 mg/kg. In summary, the present studies clearly demonstrated that both BMTBA and tetranor-DHLA were able to act as anti-inflammatory agents. This is the first study examining in vivo the anti-inflammatory properties of LA metabolites.

The Correlation Between Urinary 8-Iso-Prostaglandin F2α and Hydrogen Peroxide Toward Renal Function in T2DM Patients Consuming Sulfonylurea and Combination of Metformin-Sulfonylurea.

Science.gov (United States)

Sauriasari, Rani; Wulandari, Fitri; Nurifahmi, Rahmaningtyas; Sekar, Andisyah P; Susilo, Veronika Y

2018-01-01

Renal dysfunction is a common complication in type 2 diabetes mellitus patients associated with oxidative damage which could be characterized by 8-iso-prostaglandin F2α and hydrogen peroxide level as oxidative stress markers. The aim of our study is to determine if there is a difference in 8-iso-prostaglandin F2α and hydrogen peroxide levels between sulfonylurea and combination of metformin-sulfonylurea in diabetic patients. We also wanted to determine if these oxidative stress markers correlate with the estimated Glomerular Filtration Rate (eGFR). We conducted a cross-sectional study with inclusion of 55 patients with type 2 diabetes mellitus in Dr. Sitanala Tangerang Hospital, Indonesia with purposive sampling. The value of eGFR was obtained by serum creatinine levels, while the level of 8-iso-prostaglandin F2α was measured by ELISA and urinary hydrogen peroxide using FOX-1 (Ferrous Ion Oxidation Xylenol Orange 1). There was no difference in 8-iso-prostaglandin F2α and hydrogen peroxide level between the two groups (p=0.088 and p=0.848). Moreover, there was no difference in eGFR values between the two groups, measured by Cockroft-Gault, MDRD, and CKD-EPI. 8-iso-prostaglandin F2α (n=55) was positively correlated with eGFR based on Cockroft-Gault (r=0.382; p=0.009), whereas urinary hydrogen peroxide (n=47) also generate significant positive correlation with eGFR based on the MDRD equation (r=0.326; p=0.021). Linear regression analysis showed that 8-iso-prostaglandin F2α is the most predictive factor and the only significant factor for eGFR in Cockroft-Gault, MDRD and also CKDEPI, even after controlled by gender, age, BMI, HbA1c, systole, and H2O2. The two treatments did not have any significant differences in antioxidant activity. However, an increase of urinary 8-iso-prostaglandin F2. and hydrogen peroxide which correlates with eGFR in the total sample may play a significant role in the pathophysiology of diabetic nephropathy. Copyright© Bentham Science

Effects of epidermal growth factor, interleukin 1 and nitric oxide on prostaglandin production by guinea-pig uterus.

Science.gov (United States)

Keeble, J E; Poyser, N L

2002-08-01

Initial experiments in the present study investigated the effects of epidermal growth factor (EGF), interleukin 1beta (IL-1beta) and sodium nitroprusside (a nitric oxide donor) on the output of prostaglandins from guinea-pig uterus on day 7 of the oestrous cycle. Superfusion of day 7 guinea-pig uterus in vitro with either EGF or sodium nitroprusside increased the output of PGF(2alpha) and 6-keto-PGF(1alpha), but not of PGE(2). IL-1beta had no effect on the output of these three prostaglandins. EGF still increased the output of PGF(2alpha), but did not increase the output of 6-keto-PGF(1alpha) in a calcium-depleted superfusate. Subsequent experiments investigated the effect of sodium nitroprusside on contractile activity of day 7 guinea-pig uterus. Basal spontaneous activity of both the intact uterus and isolated myometrium superfused in vitro was low. Sodium nitroprusside increased the contractile activity of these tissues two- to fourfold. EGF did not affect the contractile activity of the uterus, indicating that sodium nitroprusside-induced contractions are not due to increased prostaglandin production. Overall, the findings indicate that EGF and nitric oxide may act as mediators in the mechanism by which oestradiol acting on a progesterone-primed uterus stimulates the increase in PGF(2alpha) production by the guinea-pig uterus necessary for luteolysis. Nitric oxide may increase the spontaneous activity of the uterus when this activity is low.

An evaluation of prostaglandin E2 vaginal gel use in practice.

Science.gov (United States)

Taylor, S J; Peat, J K; Armour, C L

1999-08-01

The purpose of this study was to investigate the effectiveness of prostaglandin E2 vaginal gel as used in practice, rather than its efficacy as assessed in randomised, controlled, clinical trials. This product is used to ripen the cervix prior to induction of labour, sometimes making unnecessary the use of the standard treatment for induction, artificial rupture of the membranes (ARM) plus oxytocin. In this study, effectiveness of the gel was assessed in terms of changes in mode of delivery, and in particular the risk of Caesarean section. An historical control was used and the risk of Caesarean section for women induced in the 1990/91 (before the introduction of the gel) was compared with that for women induced in 1992/93 (after the introduction of the gel). Maternal characteristics which may have been different in the two groups and factors which might influence the risk of Caesarean section were controlled for statistically using logistic regression, thus reducing any bias towards one group. After adjusting for the factors which had a significant effect on the process of labour from induction to birth, it was found that the risk of Caesarean section was not significantly lower in the 1992/93-time period, when the gel was in regular use, from that in the 2 years prior to its introduction (Odds ratio 1.09, CI95% 0.88, 1.36). Following the introduction of PGE2 gel, no difference in effectiveness, as measured in terms of mode of delivery, was detected in this study of practice, which included patients with more complex obstetric problems.

Dermal absorption of the insecticide lindane (1 delta, 2 delta, 3 beta, 4 delta, 5 delta, 6 beta-hexachlorocyclohexane) in rats and rhesus monkeys: Effect of anatomical site

International Nuclear Information System (INIS)

Moody, R.P.; Ritter, L.

1989-01-01

Dermal absorption of the insecticide lindane (1 delta, 2 delta, 3 beta, 4 delta, 5 delta, 6 beta-hexachlorocyclohexane) was determined in rats and rhesus monkeys. Lindane is in widespread use as a 1% cream or lotion scabicide formulation and as a 1% miticide shampoo for body lice control in humans. Results obtained following our in vivo dermal absorption procedure demonstrated that 18 +/- 4.1%, 34 +/- 5.2%, and 54 +/- 26.3% of the applied dose was absorbed following topical applications at a rate of 1.5 micrograms/cm2 (6.2 micrograms/100 microliters of acetone) of the 14C-labeled pesticide to 4.2-cm2 regions of the forearm (n = 8), forehead (n = 7), and palm (n = 4) of rhesus monkeys, respectively. Dose sites were washed with soapy water 24 h posttreatment. Comparative studies in rats (n = 5) dosed middorsally demonstrated 31 +/- 9.5% absorption. Statistical analysis of the 14C excretion kinetics demonstrated slower clearance of lindane from rats than monkey forearm, forehead, or palm. Intramuscular (im) injections of 14C-lindane gave 52 +/- 7.1% recovery in monkey (n = 8) and 64 +/- 5.9% in rats (n = 5), suggesting body storage of this lipophilic chemical

Observation of the D, E and delta mesons in pi /sup -/p interactions at 12 and 15 GeV/c

CERN Document Server

Corden, M J; Bellamy, E H; Corbett, I F; Dagan, S; Dowell, John D; Esterling, R J; Garvey, J; Gnat, Y; Green, M G; Harnew, N; Jobes, M; Kenyon, I R; Lipman, Norman H; Lister, J B; Lister, J R; Litchfield, P J; Mawson, J; McMahon, T J; Robertson, A W; Stacey, B J; Strong, J A; Sumorok, K; Thomas, D H

1978-01-01

The authors have observed the D(1285), E(1420) and delta (975) mesons produced in 12 and 15 GeV/c pi /sup -/p interactions at the CERN Omega Spectrometer. Production cross sections and decay branching ratios are presented. Analysis of the decay D(1285) to delta (975) pi favours a spin parity assignment of 1/sup +/. (24 refs).

Expression of prostaglandin synthases (pgds and pges) during zebrafish gonadal differentiation

DEFF Research Database (Denmark)

Jørgensen, Anne; Nielsen, John E; Nielsen, Betina Frydenlund

2010-01-01

The present study aimed at elucidating whether the expression pattern of the membrane bound form of prostaglandin E2 synthase (pges) and especially the lipocalin-type prostaglandin D2 synthase (pgds) indicates involvement in gonadal sex differentiation in zebrafish as has previously been found....... In this study, a sexually dimorphic expression of pgds was found in gonads of adult zebrafish with expression in testis but not in ovaries. To determine whether the sex-specific expression pattern of pgds was present in gonads of juvenile zebrafish and therefore could be an early marker of sex in zebrafish, we...... microdissected gonads from four randomly selected individual zebrafish for every second day in the period 2-20 days post hatch (dph) and 0-1 dph. The temporal expression of pgds and pges was investigated in the microdissected gonads, however, no differential expression that could indicate sex-specific difference...

The role of prostaglandins in livestock production | Okon | Global ...

African Journals Online (AJOL)

... synthesized) fashion. Prostaglandins are therefore regarded as essential mediators of female reproductive processes, hence, this paper seeks to review the role of Prostaglandins which is exploited in livestock production especially oestrus synchronization and induced parturition. KEYWORDS: Prostaglandins, Production ...

Prostaglandin E2 Stimulates the Expansion of Regulatory Hematopoietic Stem and Progenitor Cells in Type 1 Diabetes

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Moufida Ben Nasr

2018-06-01

Full Text Available Hematopoietic stem and progenitor cells (HSPCs are multipotent stem cells that have been harnessed as a curative therapy for patients with hematological malignancies. Notably, the discovery that HSPCs are endowed with immunoregulatory properties suggests that HSPC-based therapeutic approaches may be used to treat autoimmune diseases. Indeed, infusion with HSPCs has shown promising results in the treatment of type 1 diabetes (T1D and remains the only “experimental therapy” that has achieved a satisfactory rate of remission (nearly 60% in T1D. Patients with newly diagnosed T1D have been successfully reverted to normoglycemia by administration of autologous HSPCs in association with a non-myeloablative immunosuppressive regimen. However, this approach is hampered by a high incidence of adverse effects linked to immunosuppression. Herein, we report that while the use of autologous HSPCs is capable of improving C-peptide production in patients with T1D, ex vivo modulation of HSPCs with prostaglandins (PGs increases their immunoregulatory properties by upregulating expression of the immune checkpoint-signaling molecule PD-L1. Surprisingly, CXCR4 was upregulated as well, which could enhance HSPC trafficking toward the inflamed pancreatic zone. When tested in murine and human in vitro autoimmune assays, PG-modulated HSPCs were shown to abrogate the autoreactive T cell response. The use of PG-modulated HSPCs may thus provide an attractive and novel treatment of autoimmune diabetes.

Specific binding of prostaglandin E2 to membrane preparations from human skin: receptor modulation by UVB-irradiation and chemical agents

International Nuclear Information System (INIS)

Lord, J.T.; Ziboh, V.A.

1979-01-01

Human skin membranes bind prostaglandin E2 (PGE2) with high affinity and specificity. This binding is inhibited by trypsin or heat treatment suggesting that PGE2 receptors have protein components. Exposure of the membranes to ultraviolet irradiation (UVB) resulted in the loss of the membrane binding capacity for PGE2. This UVB-inhibitory effect could be prevented by a known protein sulfhydryl-oxidizing agent and a known lipid anti-oxidant

Increased renal sodium absorption by inhibition of prostaglandin synthesis during fasting in healthy man. A possible role of the epithelial sodium channels

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Graffe Carolina C

2010-10-01

Full Text Available Abstract Background Treatment with prostaglandin inhibitors can reduce renal function and impair renal water and sodium excretion. We tested the hypotheses that a reduction in prostaglandin synthesis by ibuprofen treatment during fasting decreased renal water and sodium excretion by increased absorption of water and sodium via the aquaporin2 water channels and the epithelial sodium channels. Methods The effect of ibuprofen, 600 mg thrice daily, was measured during fasting in a randomized, placebo-controlled, double-blinded crossover study of 17 healthy humans. The subjects received a standardized diet on day 1, fasted at day 2, and received an IV infusion of 3% NaCl on day 3. The effect variables were urinary excretions of aquaporin2 (u-AQP2, the beta-fraction of the epithelial sodium channel (u-ENaCbeta, cyclic-AMP (u-cAMP, prostaglandin E2 (u-PGE2. Free water clearance (CH2O, fractional excretion of sodium (FENa, and plasma concentrations of vasopressin, angiotensin II, aldosterone, atrial-, and brain natriuretic peptide. Results Ibuprofen decreased u-AQP2, u-PGE2, and FENa at all parts of the study. During the same time, ibuprofen significantly increased u-ENaCbeta. Ibuprofen did not change the response in p-AVP, u-c-AMP, urinary output, and free water clearance during any of these periods. Atrial-and brain natriuretic peptide were higher. Conclusion During inhibition of prostaglandin synthesis, urinary sodium excretion decreased in parallel with an increase in sodium absorption and increase in u-ENaCbeta. U-AQP2 decreased indicating that water transport via AQP2 fell. The vasopressin-c-AMP-axis did not mediate this effect, but it may be a consequence of the changes in the natriuretic peptide system and/or the angiotensin-aldosterone system Trial Registration Clinical Trials Identifier: NCT00281762

Prostaglandin E2 enhances long-term repopulation but does not permanently alter inherent stem cell competitiveness.

Science.gov (United States)

Hoggatt, Jonathan; Mohammad, Khalid S; Singh, Pratibha; Pelus, Louis M

2013-10-24

Hematopoietic stem cell (HSC) transplantation is a lifesaving therapy for malignant and nonmalignant hematologic diseases and metabolic disorders. Although successful, hematopoietic transplantation can be hindered by inadequate stem cell number or poor engrafting efficiency. To overcome these deficits, we and others have previously reported the HSC-enhancing ability of a short-term exposure of prostaglandin E2 (PGE2); this strategy has now progressed to phase 1 clinical trials in double cord blood transplantation. To further analyze the short- and long-term effects of HSC exposure to PGE2, we followed the repopulation kinetics of PGE2-treated hematopoietic grafts through 5 serial transplantations and compared inherent long-term competitiveness in a HSC head-to-head secondary transplantation model. Treatment with PGE2 did not result in a long-term increase in HSC competitiveness, lineage bias, or enhanced proliferative potential, demonstrating that pulse exposure to PGE2 results in transient increases in HSC homing and engraftment potential.

Evaluation of DELTA(1232) components in sup 1 sup 2 C

CERN Document Server

Bystritsky, V M; Krechetov, Yu F; Saigushkin, O K; Tabachenko, A N; Schuvalov, E N; Grabmayr, R; Fiks, A I

2001-01-01

One measured cross section of sup 1 sup 2 C(gamma, pi sup + p) reaction within DELTA(1232)-isobar range. Data analysis was carried out using model taking account of both nucleon and isobar degrees of freedom of sup 1 sup 2 C nucleus. One makes a conclusion that within high transmitted pulses pi sup + p-pairs are formed during DELTA sup + sup + -isobar direct knocking-out of a nucleus. One estimated the probability to determine DELTA-isobar in sup 1 sup 2 C nucleus ground state equal to 0.018 +- 0.005 DELTA-isobar per nucleon

Prostaglandin production by melanocytic cells and the effect of alpha-melanocyte stimulating hormone.

Science.gov (United States)

Nicolaou, Anna; Estdale, Sian E; Tsatmali, Marina; Herrero, Daniel Pascual; Thody, Anthony J

2004-07-16

Prostaglandins are potent mediators of the inflammatory response and are also involved in cancer development. In this study, we show that human melanocytes and FM55 melanoma cells express cyclooxygenase-1 and -2 (COX-1 and -2) and thus have the capability to produce prostaglandins. The FM55 cells produced predominantly PGE2 and PGF2alpha, whereas the HaCaT keratinocyte cell line produced mainly PGE2. The anti-inflammatory peptide, alpha-melanocyte stimulating hormone (alpha-MSH), reduced prostaglandin production in FM55 and HaCaT cells and reversed the effect of the pro-inflammatory cytokine TNF-alpha in the former. These results indicate that melanocytes produce prostaglandins and that alpha-MSH, by inhibiting this response, may play an important role in regulating inflammatory responses in the skin.

Effect of ibuprofen on menstrual blood prostaglandin levels in dysmenorrheic women.

Science.gov (United States)

Pulkkinen, M O; Csapo, A I

1979-07-01

In a randomized crossover study 15 dysmenorrheic women were treated during two consecutive menstrual period, once with the potent prostaglandin-synthesis inhibitor: ibuprofen and once with an identical looking placebo. Each patient was medicated for 12 hours during the first day of her menstrual flow and was subsequently fitted with a cervical cup for the collection of menstrual blood during three hours. In these samples the concentrations of prostaglandin (PG)F and PGE were measured by radioimmunoassay. The patients receiving placebo had high PGF levels 135 +/- 27 ng/ml (Mean +/- S.E.) which were significnatly reduced by Ibuprofen to 24 +/- 5 ng/ml (P less than 0.001). The PGE concentrations decreased from 5 +/- 1 ng/ml to 2 +/- 1 ng/ml (P less than 0.05). Ibuprofen also reduced the menstrual pain significantly (P less than 0.001). These results substantiate the earlier conclusion that a causal relationship exists between effective treatment with PG-synthesis inhibitors and decrease in menstrual blood PG levels, intrauterine pressure and dysmenorrheic pain.

Elevated prostaglandin E metabolites and abnormal plasma fatty acids at baseline in pediatric cystic fibrosis patients: a pilot study.

Science.gov (United States)

O'Connor, Michael Glenn; Thomsen, Kelly; Brown, Rebekah F; Laposata, Michael; Seegmiller, Adam

2016-10-01

Airway inflammation is a significant contributor to the morbidity of cystic fibrosis (CF) disease. One feature of this inflammation is the production of oxygenated metabolites, such as prostaglandins. Individuals with CF are known to have abnormal metabolism of fatty acids, typically resulting in reduced levels of linoleic acid (LA) and docosahexaenoic acid (DHA). This is a randomized, double-blind, cross-over clinical trial of DHA supplementation with endpoints of plasma fatty acid levels and prostaglandin E metabolite (PGE-M) levels. Patients with CF age 6-18 years with pancreatic insufficiency were recruited. Each participant completed 3 four-week study periods: DHA at two different doses (high dose and low dose) and placebo with a minimum 4 week wash-out between each period. Blood, urine, and exhaled breath condensate (EBC) were collected at baseline and after each study period for measurement of plasma fatty acids as well as prostaglandin E metabolites. Seventeen participants were enrolled, and 12 participants completed all 3 study periods. Overall, DHA supplementation was well tolerated without significant adverse events. There was a significant increase in plasma DHA levels with supplementation, but no significant change in arachidonic acid (AA) or LA levels. However, at baseline, AA levels were lower and LA levels were higher than previously reported for individuals with CF. Urine PGE-M levels were elevated in the majority of participants at baseline, and while levels decreased with DHA supplementation, they also decreased with placebo. Urine PGE-M levels are elevated at baseline in this cohort of pediatric CF patients, but there was no significant change in these levels with DHA supplementation compared to placebo. In addition, baseline plasma fatty acid levels for this cohort showed some difference to prior reports, including higher levels of LA and lower levels of AA, which may reflect changes in clinical care, and consequently warrants further

Tumor necrosis factor alpha inhibits in vitro bovine embryo development through a prostaglandin mediated mechanism

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Jackson Lauren R

2012-03-01

Full Text Available Abstract Mastitis or other infectious diseases have been related to reduced fertility in cattle. Inflammatory cytokines such as tumor necrosis factor α (TNFα are released in response to infection and may have negative effects on embryo development. In the current study the effect of exposure to TNFα on the development of in vitro fertilized bovine embryos was examined. Indomethacin, a prostaglandin synthesis inhibitor, was used to determine if blockade of prostaglandin synthesis would alter the effects of TNFα. Ovaries were obtained from a local abattoir and immature COC were isolated from 2-10 mm follicles, in vitro matured and fertilized. After fertilization, groups of presumptive zygotes were randomly placed into either control development medium, medium containing 25 ng/mL TNFα or medium containing 25 ng/mL TNFα plus 1 μg/mL indomethacin. The proportion of blastocysts formed was assessed at day 7 of culture. Fewer embryos exposed to TNFα alone reached the blastocyst stage (17.5 ± 2.4%, P

Holocene evolution of a wave-dominated fan-delta: Godavari delta, India

Science.gov (United States)

Saito, Y.; Nageswara Rao, K.; Nagakumar, K.; Demudu, G.; Rajawat, A.; Kubo, S.; Li, Z.

2013-12-01

The Godavari delta is one of the world's largest wave-dominated deltas. The Godavari River arises in the Western Ghats near the west coast of India and drains an area of about 3.1x10^5 km^2, flowing about 1465 km southeast across the Indian peninsula to the Bay of Bengal. The Godavari delta consists of a gentle seaward slope from its apex (12 m elevation) at Rajahmundry and a coastal beach-ridge plain over a distance of about 75 km and covers ~5200 km^2 as a delta plain. The river splits into two major distributary channels, the Gautami and the Vasishta, at a barrage constructed in the mid-1800s. The coastal environment of the deltaic coast is microtidal (~1 m mean tidal range) and wave-dominated (~1.5 m mean wave height in the June-September SW monsoon season, ~0.8 m in the NE monsoon season). Models of the Holocene evolution of the Godavari delta have changed from a zonal progradation model (e.g. Nageswara Rao & Sadakata, 1993) to a truncated cuspate delta model (Nageswara Rao et al., 2005, 2012). Twelve borehole cores (340 m total length), taken in the coastal delta plain during 2010-2013, yielded more than 100 C-14 dates. Sediment facies and C-14 dates from these and previous cores and remote-sensing data support a new delta evolution model. The Holocene coastal delta plain is divided into two parts by a set of linear beach ridges 12-14 km landward from the present shoreline in the central part of the delta. The location of the main depocenter (lobe) has shifted during the Holocene from 1) the center to 2) the west, 3) east, 4) center, 5) west, and 6) east. The linear beach ridges separate the first three from the last three stages. These lobe shifts are controlled by river channel shifts near the apex. Just as the current linear shoreline of the central part of the delta and the concave-up nearshore topography are the result of coastal erosion of a cuspate delta, the linear beach ridges indicate a former eroded shoreline. An unconformity within the deltaic

Gas chromatographic--mass spectrometric quantitation of 16, 16-dimethyl-trans-delta 2-PGE1

Energy Technology Data Exchange (ETDEWEB)

Dimov, V.; Green, K.; Bygdeman, M.; Konishi, Y.; Imaki, K.; Hayashi, M.

1983-02-01

Di-deuterated and di-tritiated 16,16-dimethyl-trans-delta 2-PGE1 has been synthesized and used for development of a GC-MS method for quantitation of corresponding unlabelled drug in patient plasma. Although these carrier/internal standard molecules only contain 2 deuterium atoms the lower limit of detection at each injection is as low as about 40 pg. The maximum plasma levels of this drug following administration of vaginal suppositories used in clinical studies (1 mg 16,16-dimethyl-trans-delta 2-PGE1 methyl ester in 0.8 g Witepsol S-52) were 100-350 pg/ml i.e. in the same order of magnitude as earlier seen for 16,16-dimethyl-PGE2.

Gas chromatographic--mass spectrometric quantitation of 16, 16-dimethyl-trans-delta 2-PGE1

International Nuclear Information System (INIS)

Dimov, V.; Green, K.; Bygdeman, M.; Konishi, Y.; Imaki, K.; Hayashi, M.

1983-01-01

Di-deuterated and di-tritiated 16,16-dimethyl-trans-delta 2-PGE1 has been synthesized and used for development of a GC-MS method for quantitation of corresponding unlabelled drug in patient plasma. Although these carrier/internal standard molecules only contain 2 deuterium atoms the lower limit of detection at each injection is as low as about 40 pg. The maximum plasma levels of this drug following administration of vaginal suppositories used in clinical studies (1 mg 16,16-dimethyl-trans-delta 2-PGE1 methyl ester in 0.8 g Witepsol S-52) were 100-350 pg/ml i.e. in the same order of magnitude as earlier seen for 16,16-dimethyl-PGE2

Vasodilative effects of prostaglandin E1 derivate on arteries of nerve roots in a canine model of a chronically compressed cauda equina

Directory of Open Access Journals (Sweden)

Konno Shin-ichi

2008-04-01

Full Text Available Abstract Background Reduction of blood flow is important in the induction of neurogenic intermittent claudication (NIC in lumbar spinal canal stenosis. PGE1 improves the mean walking distance in patients with NIC type cauda equina compression. PGE1 derivate might be effective in dilating blood vessels and improving blood flow in nerve roots with chronically compressed cauda equina. The aim of this study was to assess whether PGE1 derivate has vasodilatory effects on both arteries and veins in a canine model of chronic cauda equina compression. Methods Fourteen dogs were used in this study. A plastic balloon inflated to 10 mmHg was placed under the lamina of the 7th lumbar vertebra for 1 week. OP-1206-cyclodextrin clathrate (OP-1206-CD: prostaglandin E1 derivate was administered orally. The blood vessels of the second or third sacral nerve root were identified using a specially designed surgical microscope equipped with a video camera. The diameter of the blood vessels was measured on video-recordings every 15 minutes until 90 minutes after the administration of the PGE1 derivate. Results We observed seven arteries and seven veins. The diameter and blood flow of the arteries was significantly increased compared with the veins at both 60 and 75 minutes after administration of the PGE1 derivate (p Discussion The PGE1 derivate improved blood flow in the arteries but did not induce blood stasis in the veins. Our results suggest that the PGE1 derivate might be a potential therapeutic agent, as it improved blood flow in the nerve roots in a canine model of chronic cauda equina compression.

Relationship between symmetry of porphyrinic pi-conjugated systems and singlet oxygen (1Delta g) yields: low-symmetry tetraazaporphyrin derivatives.

Science.gov (United States)

Ishii, Kazuyuki; Itoya, Hatsumi; Miwa, Hideya; Fujitsuka, Mamoru; Ito, Osamu; Kobayashi, Nagao

2005-07-07

We have investigated the excited-state properties and singlet oxygen ((1)Delta(g)) generation mechanism in phthalocyanines (4M; M = H(2), Mg, or Zn) and in low-symmetry metal-free, magnesium, and zinc tetraazaporphyrins (TAPs), that is, monobenzo-substituted (1M), adjacently dibenzo-substituted (2AdM), oppositely dibenzo-substituted (2OpM), and tribenzo-substituted (3M) TAP derivatives, whose pi conjugated systems were altered by fusing benzo rings. The S(1)(x) and S(1)(y) states (these lowest excited singlet states are degenerate in D(4)(h) symmetry) split in the low-symmetry TAP derivatives. The excited-state energies were quantitatively determined from the electronic absorption spectra. The lowest excited triplet (T(1)(x)) energies were also determined from phosphorescence spectra, while the second lowest excited triplet (T(1)(y)) states were evaluated by using the energy splitting between the T(1)(x) and T(1)(y) states previously reported (Miwa, H.; Ishii, K.; Kobayashi, N. Chem. Eur. J. 2004, 10, 4422-4435). The singlet oxygen quantum yields (Phi(Delta)) are strongly dependent on the pi conjugated system. In particular, while the Phi(Delta) value of 2AdH(2) is smallest in our system, that of 2OpH(2), an isomer of 2AdH(2), is larger than that of 4Zn, in contrast to the heavy atom effect. The relationship between the molecular structure and Phi(Delta) values can be transformed into a relationship between the S(1)(x) --> T(1)(y) intersystem crossing rate constant (k(ISC)) and the energy difference between the S(1)(x) and T(1)(y) states (DeltaE(S)(x)(T)(y)). In each of the Zn, Mg, and metal-free compounds, the Phi(Delta)/tau(F) values (tau(F): fluorescence lifetime), which are related to the k(ISC) values, are proportional to exp(-DeltaE(S)(x)(T)(y)), indicating that singlet oxygen ((1)Delta(g)) is produced via the T(1)(y) state and that the S(1)(x) --> T(1)(y) ISC process follows the energy-gap law. From the viewpoint of photodynamic therapy, our methodology

Pyometra in Bitches Induces Elevated Plasma Endotoxin and Prostaglandin F2α Metabolite Levels

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Hagman R

2006-03-01

Full Text Available Endotoxemia in bitches with pyometra can cause severe systemic effects directly or via the release of inflammatory mediators. Plasma endotoxin concentrations were measured in ten bitches suffering from pyometra with moderately to severely deteriorated general condition, and in nine bitches admitted to surgery for non-infectious reasons. Endotoxin samples were taken on five occasions before, during and after surgery. In addition, urine and uterine bacteriology was performed and hematological, blood biochemical parameters, prostaglandin F2α metabolite 15-ketodihydro-PGF2α (PG-metabolite, progesterone and oestradiol (E2-17β levels were analysed. The results confirm significantly increased plasma levels of endotoxin in bitches with pyometra and support previous reports of endotoxin involvement in the pathogenesis of the disease. Plasma concentrations of PG-metabolite were elevated in pyometra bitches and provide a good indicator of endotoxin release since the concentrations were significantly correlated to the endotoxin levels and many other hematological and chemistry parameters. The γ-globulin serum protein electrophoresis fraction and analysis of PG-metabolite can be valuable in the diagnosis of endotoxin involvement if a reliable, rapid and cost-effective test for PG-metabolite analysis becomes readily available in the future. Treatment inhibiting prostaglandin biosynthesis and related compounds could be beneficial for bitches suffering from pyometra.

Displacement waves in La2CuO(4-delta) and La(1.85)Sr(0.15)CuO(4-delta)

Science.gov (United States)

Kajitani, Tsuyoshi; Onozuka, Takashi; Yamaguchi, Yasuo; Hirabayashi, Makoto; Syono, Yasuhiko

1987-11-01

Structural investigation of orthorhombic La2CuO(4-delta) and La(1.85)Sr(0.15)CuO(4-delta) was carried out by means of X-ray and neutron diffraction on the basis of the space group Cmmm. The periodic expansion/contraction type distortion of CuO6 octahedra was found in both orthorhombic compounds. The distortion is nearly one-dimensional in La2CuO(4-delta) but is two-dimensional in La(1.85)Sr(0.15)CuO(4-delta). The existence of a charge-density wave is highly possible in the structures.

Penetration effect of prostaglandin E2 gel on oral mucosa of rats

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Rafinus Arifin

2012-09-01

Full Text Available Background: Several researches reported that Prostaglandin E2 (PGE2 injection on buccal mucosa combined with orthodontic pressure can faster tooth movement but has disadvantages such as high alveolar bone and root resorption furthermore pain from injection needle. PGE2 gel was made to better replace the lacks of injectable PGE2. Purpose: This research was aimed to prove that PGE 2 gel can penetrate rat’s oral mucosa effecting the appearance of PMN cells. Methods: This research was an in vivo laboratory experiment using 36 Sprague Dawley rats which were divided into 3 groups: normal group, topical PGE2 gel group after 1, 2, 4, 8 hours (4 subgroups, and topical gel without PGE2 group after 1, 2, 4, 8 hours (4 subgroups. Each group consists of 4 rats, therefore the total sample for all research groups were 36 rats. Gel with 25 µg/mL of PGE2 and gel without PGE2 were applied on oral mucosa for 2 minutes. Then, the rats were sacrificed after 1 hour, 2 hours, 4 hours, and 8 hours application. After that, the samples were prepared for histological examination with Hematoxyllin and Eosin. The picture were taken with OptiLab View and PMN cells amount were counted with light microscope, set 400 times of magnification. Results: Penetration effect of PGE2 gel on rat’s oral mucosa result in PMN inflammation cells distribution. One-way ANOVA showed no significant difference on PMN cells count in rats’ lower jaws between groups of normal and gel without PGE2. There was significant difference between groups of PGE2 gel and gel without PGE2 (p=0,001. PGE2 gel application showed PGE2 as inflammatory media, even though administered topically. Conclusion: PGE2 gel can penetrate rat’s oral mucosa, effecting PMN cells 1, 2, 4 and 8 hours after application of PGE2 gel.Latar belakang: Beberapa penelitian melaporkan bahwa injeksi (Prostaglandin E2 PGE2pada mukosa bukal yang dikombinasikan dengan tekanan ortodonti dapat mempercepat pergerakan gigi, tapi

On the Composition and Neutrix Composition of the Delta Function and the Function cosh^{-1}(|x|^{1/r}+1

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Brian Fisher

2017-03-01

Full Text Available Let $F$ be a distribution in $\\mathcal{D'}$ and let $f$ be a locally summable function. The composition $F(f(x$ of $F$ and $f$ is said to exist and be equal to the distribution $h(x$ if the limit of the sequence $\\{ F_{n}(f(x\\}$ is equal to $h(x$, where $F_n(x =F(x*\\delta _n(x$ for $n=1,2, \\ldots$ and $\\{\\delta_n(x\\}$ is a certain regular sequence converging to the Dirac delta function. It is proved that the neutrix composition $ \\delta^{(s}[\\cosh^{-1} (x_+^{1/r}+1] $ exists and \\beqa \\delta^{(s}[\\cosh^{-1} (x_+^{1/r}+1] = - \\sum _{k=0} ^{M-1} \\sum_{i=0}^{kr+r} {k \\choose i}{(-1^{i+k}rc_{r,s,k} \\over (kr+rk!}\\delta ^{(k}(x, for $s =M-1,M, M+1,\\ldots$ and $r=1,2,\\ldots,$ where $$c_{r,s,k}=\\sum _{j=0}^{i} {i \\choose j}{ (-1^{kr+r-i}(2j-i^{s+1}\\over 2^{s+i+1} },$$ $M$ is the smallest integer for which $s-2r+1 < 2Mr$ and $r\\le s/(2M+2.$ Further results are also proved.

Effect of aspirin and prostaglandins on the carbohydrate metabolism in albino rats.: glucose oxidation through different pathways and glycolytic enzymes

International Nuclear Information System (INIS)

Balasubramanian, A.; Ramakrishnan, S.

1980-01-01

The effect of chronic and acute doses of aspirin and prostaglandins F2α and E2 individually on the oxidation of glucose through Embden Meyerhof-TCA cycle and pentose phosphate pathways and some key glycolytic enzymes of liver were studied in male albino rats. Studies were extended to find the combined effect of PGF2α and E2 with an acute dose of aspirin. There was increased utilisation of both 1- 14 C glucose and 6- 14 C glucose on aspirin treatment. However, the metabolism through the EM-TCA pathway was more pronounced as shown by a reduced ratio of 14 CO 2 from 1- 14 C and 6- 14 C glucose. Two hepatic key glycolytic enzymes viz. hexokinase and pyruvate kinase were increased due to aspirin treatment. Withdrawal of aspirin corrected the above impaired carbohydrate metabolism in liver. Prostaglandin F2α also caused a reduction in the utilisation of 1- 14 C glucose, while PGE2 recorded an increase in the utilisation of both 1- 14 C and 6- 14 C glucose when compared to controls, indicating that different members of prostaglandins could affect metabolisms and differently. Administration of the PGs and aspirin together showed an increase in the utilisation of 6- 14 C glucose. (auth.)

Gastric bicarbonate secretion and release of prostaglandin E2 are increased in duodenal ulcer patients but not in Helicobacter pylori-positive healthy subjects

DEFF Research Database (Denmark)

Mertz-Nielsen, A; Hillingsø, Jens; Frøkiaer, H

1996-01-01

BACKGROUND: Duodenal ulcer (DU) patients have impaired proximal duodenal mucosal bicarbonate secretion at rest and in response to luminal acid with higher acid-stimulated mucosal release of prostaglandin (PG) E2 than healthy subjects. Our purpose was to determine whether this abnormality was pres......BACKGROUND: Duodenal ulcer (DU) patients have impaired proximal duodenal mucosal bicarbonate secretion at rest and in response to luminal acid with higher acid-stimulated mucosal release of prostaglandin (PG) E2 than healthy subjects. Our purpose was to determine whether this abnormality...... was present also in the stomach of DU patients. METHODS: Simultaneous determinations of gastric and duodenal bicarbonate secretion and luminal release of PGE2 were performed in 16 healthy volunteers (5 Helicobacter pylori-positive) and 8 inactive DU patients (all H. pylori-positive). RESULTS: In healthy...... for the abnormally high gastric secretion of bicarbonate in inactive DU patients. The defective duodenal secretion of bicarbonate observed in these patients may be a consequence of previous ulceration rather than the mere presence of H. pylori infection....

Effect of human milk prostaglandins and lactoferrin on respiratory syncytial virus and rotavirus.

Science.gov (United States)

Grover, M; Giouzeppos, O; Schnagl, R D; May, J T

1997-03-01

The effect of lactoferrin and prostaglandins E and F2 alpha on the growth of rotavirus and respiratory syncytial virus in cell culture was investigated. Lactoferrin inhibited the growth of respiratory syncytial virus at a concentration tenfold lower than that normally present in human milk. The prostaglandins had no effect on either virus growth, even at a concentration of 100-fold more than that found in human milk. Lactoferrin may have some antiviral properties in human milk in addition to its known antibacterial functions.

Phospholipase C-{delta}{sub 1} regulates interleukin-1{beta} and tumor necrosis factor-{alpha} mRNA expression

Energy Technology Data Exchange (ETDEWEB)

Chung, Eric; Jakinovich, Paul; Bae, Aekyung [Department of Anesthesiology, Health Sciences Center L4 Rm 081, Stony Brook University, Stony Brook, NY 11794 (United States); Rebecchi, Mario, E-mail: Mario.rebecchi@SBUmed.org [Department of Anesthesiology, Health Sciences Center L4 Rm 081, Stony Brook University, Stony Brook, NY 11794 (United States)

2012-10-01

Phospholipase C-{delta}{sub 1} (PLC{delta}{sub 1}) is a widely expressed highly active PLC isoform, modulated by Ca{sup 2+} that appears to operate downstream from receptor signaling and has been linked to regulation of cytokine production. Here we investigated whether PLC{delta}{sub 1} modulated expression of the pro-inflammatory cytokines interleukin-1{beta} (IL-1{beta}), tumor necrosis factor-{alpha} (TNF-{alpha}) and interleukin-6 (IL-6) in rat C6 glioma cells. Expression of PLC{delta}{sub 1} was specifically suppressed by small interfering RNA (siRNA) and the effects on cytokine mRNA expression, stimulated by the Toll-like receptor (TLR) agonist, lipopolysaccharide (LPS), were examined. Real-time polymerase chain reaction (RT-PCR) results showed that PLC{delta}{sub 1} knockdown enhanced expression IL-1{beta} and tumor necrosis factor-{alpha} (TNF-{alpha}) mRNA by at least 100 fold after 4 h of LPS stimulation compared to control siRNA treatment. PLC{delta}{sub 1} knock down caused persistently high Nf{kappa}b levels at 4 h of LPS stimulation compared to control siRNA-treated cells. PLC{delta}{sub 1} knockdown was also associated with elevated nuclear levels of c-Jun after 30 min of LPS stimulation, but did not affect LPS-stimulated p38 or p42/44 MAPK phosphorylation, normally associated with TLR activation of cytokine gene expression; rather, enhanced protein kinase C (PKC) phosphorylation of cellular proteins was observed in the absence of LPS stimulation. An inhibitor of PKC, bisindolylmaleimide II (BIM), reversed phosphorylation, prevented elevation of nuclear c-Jun levels, and inhibited LPS-induced increases of IL-1{beta} and TNF-{alpha} mRNA's induced by PLC{delta}{sub 1} knockdown. Our results show that loss of PLC{delta}{sub 1} enhances PKC/c-Jun signaling and up-modulates pro-inflammatory cytokine gene transcription in concert with the TLR-stimulated p38MAPK/Nf{kappa}b pathway. Our findings are consistent with the idea that PLC{delta}{sub 1} is a

Synthesis of triated N1'-alkyl derivatives of the delta opioid receptor ligand naltrindole

International Nuclear Information System (INIS)

Lever, J.R.; Johnson, S.M.

1997-01-01

Tritiated N1'-methyl and N1'-ethyl analogues of naltrindole (NTI) have been synthesized for evaluation as radioligands for studies of delta opioid receptors. The two N1'-alkyl-5',7'-dibromoNTI precursors for radiolabeling were prepared by base-promoted alkylation of 2,4-dibromophenylhydrazine with either iodomethane or iodoethane followed by condensation with naltrexone using the Fischer indole synthesis. Catalytic debromotritiation followed by HPLC purification afforded [ 3 H]MeNTI (17.3 Ci/mmol) and [ 3 H]EtNTI (22.5 Ci/mmol) with high chemical and radiochemical purities (≥ 99.8%). (author)

Lepeophtheirus salmonis: characterization of prostaglandin E(2) in secretory products of the salmon louse by RP-HPLC and mass spectrometry.

Science.gov (United States)

Fast, M D; Ross, N W; Craft, C A; Locke, S J; MacKinnon, S L; Johnson, S C

2004-01-01

Lepeophtheirus salmonis is an ectoparasitic copepod that causes serious disease outbreaks in both wild and farmed salmonids. As the relationship between L. salmonis and its hosts is not well understood, the current investigation was undertaken to investigate whether any immunomodulatory compounds could be identified from secretions of L. salmonis. By incubating live L. salmonis adults with the neurotransmitter dopamine in seawater, we were able to obtain secretions from the parasite. These were analyzed by RP-HPLC column, as well as LC-MS. L. salmonis secretions contained a compound with the same retention time and mass of PGE(2). The identity of this compound as PGE(2) was confirmed by MS-in source dissociation. The concentrations of PGE(2) in L. salmonis secretions ranged from 0.2 to 12.3 ng/individual and varied with incubation temperature and time kept off the host. Prostaglandin E(2) is a potent vasodilator and thought to aid in parasite evasion from host immune responses. This is the first reported evidence of prostaglandin production in parasitic copepod secretions and its implications for the host-parasite relationship are discussed.

Fetal placental prostaglandin metabolism in the peripartum cow

International Nuclear Information System (INIS)

Gross, T.S.; Williams, W.F.; Lewis, G.S.

1986-01-01

Previous results demonstrate that fetal placental tissue synthesizes prostaglandin E (PGE) prior to parturition. When placental membranes do not separate postpartum, PGE synthesis is maintained, while prostaglandin F (PGF) synthesis predominates when the membranes separate. Concurrent with separation is a decline in fetal placental binucleate cell (BNC) numbers. These data suggest a fetal placental conversion of PGE to PGF. For this experiment, placentomes were collected at ten days prepartum (PRE, n=12) and within 1 hr postpartum. Nine of the postpartum animals had fetal membrane separation within 12 hr postpartum (S) and eight did not exhibit membrane separation (NS). For each placentome, fetal (villi) components were manually isolated and examined for the ability to interconvert 3 H labeled PGE 2 and PGF 2 . All villi were unable to convert PGE 2 to PGF 2 (P > .05). The PRE and NS villi were able to convert PGF 2 to PGE 2 (P 2 to PGE 2 (P 2 to PGE 2 also declines (P < .05). These data suggest that peripartum fetal placental tissue might synthesize PGF which is then converted to PGE. It is possible that the BNC are directly converting PGF to PGE or that they are modulating this conversion. Therefore, with a decline in BNC numbers, PGF synthesis would predominate

The roles of the cyclo-oxygenases types one and two in prostaglandin synthesis in human fetal membranes at term.

Science.gov (United States)

Sawdy, R J; Slater, D M; Dennes, W J; Sullivan, M H; Bennett, P R

2000-01-01

The aim of this study was to determine the relative contributions of cyclo-oxygenase (COX) types 1 and 2 to prostaglandin synthesis at term. Fetal membranes were collected from 6 pregnancies after elective caesarean section at term, prior to labour. The presence of COX-1 and COX-2 protein was determined using Western analysis. The relative contributions of the two isoforms of COX to prostaglandin synthesis were determined by incubation of fetal membrane discs with either a COX-2 selective inhibitor, SC236, or a COX-1 selective inhibitor, SC560, and measurement of prostaglandin release during 24 h using enzyme-linked immuno-sorbent assay (ELISA). Both COX-1 and COX-2 protein were demonstrated in amnion and chorion-decidua. The COX-2 selective inhibitor, SC-236, significantly reduced prostaglandin synthesis, both in its COX-2 specific and higher, non-specific concentration ranges. The COX-1 selective inhibitor, SC-560, had no effect upon prostaglandin synthesis in its COX-1 specific concentration range, but did significantly reduce prostaglandin synthesis at higher, non-selective concentrations. Fetal membranes contain both COX-1 and COX-2 at term, but only COX-2 contributes towards prostaglandin synthesis. COX-2 selective NSAI drugs will be as effective as non-selective agents in inhibition of fetal membrane prostaglandin synthesis and may represent a new strategy for tocolysis. Copyright 2000 Harcourt Publishers Ltd.

17 CFR 270.22e-2 - Pricing of redemption requests in accordance with Rule 22c-1.

Science.gov (United States)

2010-04-01

... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Pricing of redemption requests in accordance with Rule 22c-1. 270.22e-2 Section 270.22e-2 Commodity and Securities Exchanges....22e-2 Pricing of redemption requests in accordance with Rule 22c-1. An investment company shall not be...

Cyclo-oxygenase-2 mediated prostaglandin release regulates blood flow in connective tissue during mechanical loading in humans

DEFF Research Database (Denmark)

Langberg, H; Boushel, Robert Christopher; Skovgaard, D

2003-01-01

prior to the experiment) or COX unspecific (n = 8, indomethacin 100 mg (12 and 1 h pre-experiment) and acetyl salicylic acid 500 mg day-1 for 3 days pre-experiment). Prostaglandin E2 (PGE2) concentration was determined by microdialysis and blood flow by 133Xe washout. In C, interstitial PGE2 rose from...

Breed distribution of the ABCB1-1Delta (multidrug sensitivity) polymorphism among dogs undergoing ABCB1 genotyping.

Science.gov (United States)

Mealey, Katrina L; Meurs, Kathryn M

2008-09-15

To evaluate the breed distribution of the ABCB1-1Delta polymorphism in a large number of dogs in North America, including dogs of several herding breeds in which this polymorphism has been detected and other breeds in which this polymorphism has not yet been identified. Cross-sectional study. 5,368 dogs from which buccal swab samples were collected for purposes of ABCB1 genotyping. From May 1, 2004, to September 30, 2007, DNA specimens derived from buccal swab samples collected from 5,368 dogs underwent ABCB1 genotyping. These data were reviewed, and results for each dog were recorded in a spreadsheet, along with the dog's breed. The genotypes for each breed were tallied by use of a sorting function. The ABCB1-1Delta allele was identified in 9 breeds of dogs and in many mixed-breed dogs. Breeds that had the ABCB1-1Delta allele included Collie, Longhaired Whippet, Australian Shepherd (standard and miniature), Shetland Sheepdog, Old English Sheepdog, Border Collie, Silken Windhound, and German Shepherd Dog (a breed in which this mutation had not been detected previously). The ABCB1-1Delta polymorphism is associated with increased susceptibility to many adverse drug reactions and with suppression of the hypothalamic-pituitary-adrenal axis and is present in many herding breeds of dog. Veterinarians should be familiar with the breeds that have the ABCB1-1Delta polymorphism to make appropriate pharmacologic choices for these patients.

Quark sea and the. delta. I=1/2 rule

Energy Technology Data Exchange (ETDEWEB)

Donoghue, J F [Carnegie-Mellon Univ., Pittsburgh, Pa. (USA). Dept. of Physics; Golowich, E [Massachusetts Univ., Amherst (USA)

1977-08-29

The effect on nonleptonic processes of quark-antiquark pairs due to quantum chromodynamics is studied. Their presence improves agreement between theory and experiment for hyperon decays. In kaon decays a new ..delta..I=1/2 contribution is found, but ..delta..I=3/2 effects are still too large to be in agreement.

Stimulation of accumbal GABAA receptors inhibits delta2-, but not delta1-, opioid receptor-mediated dopamine efflux in the nucleus accumbens of freely moving rats.

Science.gov (United States)

Aono, Yuri; Kiguchi, Yuri; Watanabe, Yuriko; Waddington, John L; Saigusa, Tadashi

2017-11-15

The nucleus accumbens contains delta-opioid receptors that may reduce inhibitory neurotransmission. Reduction in GABA A receptor-mediated inhibition of accumbal dopamine release due to delta-opioid receptor activation should be suppressed by stimulating accumbal GABA A receptors. As delta-opioid receptors are divided into delta2- and delta1-opioid receptors, we analysed the effects of the GABA A receptor agonist muscimol on delta2- and delta1-opioid receptor-mediated accumbal dopamine efflux in freely moving rats using in vivo microdialysis. Drugs were administered intracerebrally through the dialysis probe. Doses of compounds indicate total amount administered (mol) during 25-50min infusions. The delta2-opioid receptor agonist deltorphin II (25.0nmol)- and delta1-opioid receptor agonist DPDPE (5.0nmol)-induced increases in dopamine efflux were inhibited by the delta2-opioid receptor antagonist naltriben (1.5nmol) and the delta1-opioid receptor antagonist BNTX (150.0pmol), respectively. Muscimol (250.0pmol) inhibited deltorphin II (25.0nmol)-induced dopamine efflux. The GABA A receptor antagonist bicuculline (50.0pmol), which failed to affect deltorphin II (25.0nmol)-induced dopamine efflux, counteracted the inhibitory effect of muscimol on deltorphin II-induced dopamine efflux. Neither muscimol (250.0pmol) nor bicuculline (50.0 and 500.0pmol) altered DPDPE (5.0nmol)-induced dopamine efflux. The present results show that reduction in accumbal GABA A receptor-mediated inhibition of dopaminergic activity is necessary to produce delta2-opioid receptor-induced increase in accumbal dopamine efflux. This study indicates that activation of delta2- but not delta1-opioid receptors on the cell bodies and/or terminals of accumbal GABAergic interneurons inhibits GABA release and, accordingly, decreases GABA A receptor-mediated inhibition of dopaminergic terminals, resulting in enhanced accumbal dopamine efflux. Copyright © 2017 Elsevier B.V. All rights reserved.

Assessing the usefulness of prostaglandin E2 (Cervidil) for transcervical artificial insemination in ewes.

Science.gov (United States)

Bartlewski, Pawel M; Candappa, Ivanka B R

2015-12-01

The underlying theme of this study involved the evaluation of the dilatory effects of prostaglandin E2 on the ovine cervix and thus the assessment of its potential applicability to transcervical artificial insemination (TCAI) in ewes. A novel method of prostaglandin E2 administration (controlled slow-release vaginal inserts) was examined, and the practical implications of this approach including cervical penetrability and posttreatment pregnancy rates were evaluated. The Guelph method of TCAI was performed during the seasonal anestrus (n = 40) and the breeding season (n = 40) on multiparous Rideau Arcott × Polled Dorset ewes, with or without the pretreatment with Cervidil (for a duration of 12 hours or 24 hours before TCAI). Cervical penetration rates averaged 82.5% (66 of 80), and they varied neither (P > 0.05) between the two seasons nor between Cervidil-treated ewes and their respective controls. Cervidil priming significantly reduced the total time required for TCAI during the breeding season in comparison with controls (54 vs. 98 seconds), especially after the 24-hour exposure (38 vs. 108 seconds). The time taken to traverse the uterine cervix was negatively correlated (P ewes. Four out of 36 (11%) successfully penetrated ewes in the breeding season (three ewes allocated to the 12-hour control group and one ewe that had received Cervidil for 12 hours) became pregnant and carried the lambs to term. Vaginal mucus impedance at TCAI was significantly and positively correlated with the total time required to complete the procedure in cyclic ewes, and the negative correlation between vaginal mucus impedance and total time values at the time of controlled intravaginal drug release device removal approached to significance in anestrous ewes. The present results indicate a moderate benefit of using Cervidil for inducing cervical dilation before TCAI in ewes, mainly in the breeding season. The specific reason(s) for impaired fertility after the TCAI using

Displacement waves in La/sub 2/CuO(4-delta) and La(1. 85)Sr(0. 15)CuO(4-delta)

Energy Technology Data Exchange (ETDEWEB)

Kajitani, T.; Onozuka, T.; Yamaguchi, Y.; Hirabayashi, M.; Syono, Y.

1987-11-01

Structural investigation of orthorhombic La/sub 2/CuO(4-delta) and La(1.85)Sr(0.15)CuO(4-delta) was carried out by means of X-ray and neutron diffraction on the basis of the space group Cmmm. The periodic expansion/contraction type distortion of CuO6 octahedra was found in both orthorhombic compounds. The distortion is nearly one-dimensional in La/sub 2/CuO(4-delta) but is two-dimensional in La(1.85)Sr(0.15)CuO(4-delta). The existence of a charge-density wave is highly possible in the structures. 20 references.

Prostaglandin Hsynthase immunoreactivity in human gut. An immunohistochemical study

DEFF Research Database (Denmark)

Mikkelsen, Hanne Birte; Rumessen, Jüri Johannes; Qvortrup, Klaus

1991-01-01

Anatomy, prostaglandin H-synthase, smooth muscle cells, intestine, muscularis externa, immunohistochemistry......Anatomy, prostaglandin H-synthase, smooth muscle cells, intestine, muscularis externa, immunohistochemistry...

Prostaglandin E2 produced by Entamoeba histolytica binds to EP4 receptors and stimulates interleukin-8 production in human colonic cells.

Science.gov (United States)

Dey, Indranil; Chadee, Kris

2008-11-01

Entamoeba histolytica pathogenesis in the colon occurs in a stepwise fashion. It begins with colonization of the mucin layer, which is followed by stimulation of a proinflammatory response that causes nonspecific tissue damage that may facilitate parasite invasion of the underlying colonic mucosa. Unfortunately, the parasite and/or host factors that stimulate a proinflammatory response in the gut are poorly understood. In this study, we found that live E. histolytica or secretory or proteins (SP) and soluble ameba components (SAP) can markedly increase interleukin-8 (IL-8) mRNA expression and protein production in colonic epithelial cells. The IL-8-stimulating molecule produced by live amebae was identified as prostaglandin E(2) (PGE(2)) as trophozoites treated with cyclooxygenase inhibitors inhibited the biosynthesis of PGE(2) and eliminated IL-8 production induced by live parasites or ameba components. Moreover, using specific prostaglandin EP2 and EP4 receptor agonists and antagonists, we found that PGE(2) binds exclusively through EP4 receptors in colonic epithelial cells to stimulate IL-8 production. Silencing of EP4 receptors with EP4 small interfering RNA completely eliminated SP- and SAP-induced IL-8 production. These studies identified bioactive PGE(2) as a one of the major virulence factors produced by E. histolytica that can stimulate the potent neutrophil chemokine and activator IL-8, which can trigger an acute host inflammatory response. Thus, the induction of IL-8 production in response to E. histolytica-derived PGE(2) may be a mechanism that explains the initiation and amplification of acute inflammation associated with intestinal amebiasis.

Magneto-caloric effect in the pseudo-binary intermetallic YPrFe{sub 17} compound

Energy Technology Data Exchange (ETDEWEB)

Alvarez, Pablo [Departamento de Fisica, Universidad de Oviedo, Calvo Sotelo, s/n, 33007 Oviedo (Spain); Gorria, Pedro, E-mail: pgorria@uniovi.es [Departamento de Fisica, Universidad de Oviedo, Calvo Sotelo, s/n, 33007 Oviedo (Spain); Sanchez Llamazares, Jose L. [Division de Materiales Avanzados, Instituto Potosino de Investigacion Cientifica y Tecnologica, Camino a la presa San Jose 2055, CP 78216, San Luis Potosi (Mexico); Perez, Maria J. [Departamento de Fisica, Universidad de Oviedo, Calvo Sotelo, s/n, 33007 Oviedo (Spain); Franco, Victorino [Departamento de Fisica de la Materia Condensada, ICMSE-CSIC, Universidad de Sevilla, P.O. Box 1065, 41080 Sevilla (Spain); Reiffers, Marian; Kovac, Jozef [Institute of Experimental Physics, Watsonova 47, SK-04001 Kosice (Slovakia); Puente-Orench, Ines [Institute Laue Langevin, 6 rue Jules Horowitz, 38042 Grenoble (France); Blanco, Jesus A. [Departamento de Fisica, Universidad de Oviedo, Calvo Sotelo, s/n, 33007 Oviedo (Spain)

2011-12-15

Highlights: Black-Right-Pointing-Pointer YPrFe{sub 17} exhibits a broad {Delta}S{sub M}(T) associated with the ferro-to-paramagnetic phase transition (T{sub C} Almost-Equal-To 290 K). Black-Right-Pointing-Pointer We obtain |{Delta}S{sub M}| Almost-Equal-To 2.3 J kg{sup -1} K{sup -1} and RCP Almost-Equal-To 100 J kg{sup -1}for a magnetic field change of 1.5 T. Black-Right-Pointing-Pointer A single master curve for {Delta}S{sub M} is found when compared with other isostructural R{sub 2}Fe{sub 17} binary alloys. - Abstract: We have synthesized the intermetallic YPrFe{sub 17} compound by arc-melting. X-ray and neutron powder diffraction show that the crystal structure is rhombohedral with R3{sup Macron }m space group (Th{sub 2}Zn{sub 17}-type). The investigated compound exhibits a broad isothermal magnetic entropy change {Delta}S{sub M}(T) associated with the ferro-to-paramagnetic phase transition (T{sub C} Almost-Equal-To 290 K). The |{Delta}S{sub M}| ( Almost-Equal-To 2.3 J kg{sup -1} K{sup -1}) and the relative cooling power ( Almost-Equal-To 100 J kg{sup -1}) have been calculated for applied magnetic field changes up to 1.5 T. A single master curve for {Delta}S{sub M} under different values of the magnetic field change can be obtained by a rescaling of the temperature axis. The results are compared and discussed in terms of the magneto-caloric effect in the isostructural R{sub 2}Fe{sub 17} (R = Y, Pr and Nd) binary intermetallic alloys.

The Multiple Faces of Prostaglandin E2 G-Protein Coupled Receptor Signaling during the Dendritic Cell Life Cycle

Directory of Open Access Journals (Sweden)

Alessandra Cambi

2013-03-01

Full Text Available Many processes regulating immune responses are initiated by G-protein coupled receptors (GPCRs and report biochemical changes in the microenvironment. Dendritic cells (DCs are the most potent antigen-presenting cells and crucial for the regulation of innate and adaptive immune responses. The lipid mediator Prostaglandin E2 (PGE2 via four GPCR subtypes (EP1-4 critically regulates DC generation, maturation and migration. The role of PGE2 signaling in DC biology was unraveled by the characterization of EP receptor subtype expression in DC progenitor cells and DCs, the identification of the signaling pathways initiated by these GPCR subtypes and the classification of DC responses to PGE2 at different stages of differentiation. Here, we review the advances in PGE2 signaling in DCs and describe the efforts still to be made to understand the spatio-temporal fine-tuning of PGE2 responses by DCs.

Prostaglandin E2 Activates YAP and a Positive-Signaling Loop to Promote Colon Regeneration After Colitis but Also Carcinogenesis in Mice.

Science.gov (United States)

Kim, Han-Byul; Kim, Minchul; Park, Young-Soo; Park, Intae; Kim, Tackhoon; Yang, Sung-Yeun; Cho, Charles J; Hwang, DaeHee; Jung, Jin-Hak; Markowitz, Sanford D; Hwang, Sung Wook; Yang, Suk-Kyun; Lim, Dae-Sik; Myung, Seung-Jae

2017-02-01

Prostaglandin E 2 (PGE 2 ) is mediator of inflammation that regulates tissue regeneration, but its continual activation has been associated with carcinogenesis. Little is known about factors in the PGE 2 signaling pathway that contribute to tumor formation. We investigated whether yes-associated protein 1 (YAP1), a transcriptional co-activator in the Hippo signaling pathway, mediates PGE 2 function. DLD-1 and SW480 colon cancer cell lines were transfected with vectors expressing transgenes or small hairpin RNAs and incubated with recombinant PGE 2 , with or without pharmacologic inhibitors of signaling proteins, and analyzed by immunoblot, immunofluorescence, quantitative reverse-transcription polymerase chain reaction, transcriptional reporter, and proliferation assays. Dextran sodium sulfate (DSS) was given to induce colitis in C57/BL6 (control) mice, as well as in mice with disruption of the hydroxyprostaglandin dehydrogenase 15 gene (15-PGDH-knockout mice), Yap1 gene (YAP-knockout mice), and double-knockout mice. Some mice also were given indomethacin to block PGE 2 synthesis. 15-PGDH knockout mice were crossed with mice with intestine-specific disruption of the salvador family WW domain containing 1 gene (Sav1), which encodes an activator of Hippo signaling. We performed immunohistochemical analyses of colon biopsy samples from 26 patients with colitis-associated cancer and 51 age-and sex-matched patients with colorectal cancer (without colitis). Incubation of colon cancer cell lines with PGE 2 led to phosphorylation of cyclic adenosine monophosphate-responsive element binding protein 1 and increased levels of YAP1 messenger RNA, protein, and YAP1 transcriptional activity. This led to increased transcription of the prostaglandin-endoperoxide synthase 2 gene (PTGS2 or cyclooxygenase 2) and prostaglandin E-receptor 4 gene (PTGER4 or EP4). Incubation with PGE 2 promoted proliferation of colon cancer cell lines, but not cells with knockdown of YAP1. Control mice

Expression of prostaglandin synthases (pgds and pges) duringzebrafishgonadal differentiation

DEFF Research Database (Denmark)

Jørgensen, Anne; Nielsen, John E.; Nielsen, Betina F.

2010-01-01

The present study aimed at elucidating whether the expression pattern of the membrane bound form of prostaglandin E-2 synthase (pges) and especially the lipocalin-type prostaglandin D-2 synthase (pgds) indicates involvement in gonadal sex differentiation in zebrafish as has previously been found...... In this study, a sexually dimorphic expression of pgds was found in gonads of adult zebrafish with expression in testis but not in ovaries. To determine whether the sex-specific expression pattern of pgds was present in gonads of juvenile zebrafish and therefore could be an early marker of sex in zebrafish, we...... microdissected gonads from four randomly selected individual zebrafish for every second day in the period 2-20 days post hatch (dph) and 0-1 dph The temporal expression of pgds and pges was investigated in the microdissected gonads, however, no differential expression that could indicate sex-specific difference...

Perfusion of the isolated rat brain with (/sup 14/C)-. delta. /sup 1/-tetrahydrocannabinol

Energy Technology Data Exchange (ETDEWEB)

Martin, B; Agurell, S [Dept. of Pharmacognosy, Faculty of Pharmacy, BMC, Uppsala (Sweden); Krieglstein, J; Rieger, H

1977-12-01

There is controversy over whether ..delta../sup 1/-tetrahydrocannabinol (..delta../sup 1/-THC) or its metabolites is responsible for the behavioural and cardiovascular effects of cannabis. It has been shown that, even in the absence of metabolism, ..delta../sup 1/-THC was capable of altering the EEG of isolated perfused rat brain, and must therefore contribute to the psychoactivity of cannabis. TLC studies showed no evidence for brain metabolism of (/sup 14/C)-..delta../sup 1/-THC, and in particular the 7-hydroxylated metabolite (7-OH-..delta../sup 1/-THC) could not be detected. A disproportionate amount of CNS activity in the rat cannot therefore be attributed to 7-OH-..delta../sup 1/-THC on the basis that it is formed at or near its locus of action.

Morphodynamics of the Manyema tidal delta 1 LIST OF TABLES ...

African Journals Online (AJOL)

Kheira Kortenbout

Morphodynamics of the Manyema tidal delta. 1. LIST OF ... Location of Manyema Creek and its associated tidal delta platform at Kunduchi. Fig. 2. ... platform. Beachcomber. Hotel. Whitesands. Hotel. Kunduchi. Beach Hotel. Giraffe. Hotel. INDIAN. OCEAN. Mombasa. Dar es. Salaam. KUNDUCHI. KENYA. TANZANIA.

Influence of prostaglandin analogues on epithelial cell proliferation and xenograft growth.

Science.gov (United States)

Tutton, P J; Barkla, D H

1980-01-01

The influence of two prostaglandin (PG) analogues, 16,16-dimethyl PG E2 and 16,16-dimethyl PG F2 alpha and of the cyclo-oxygenase inhibitor, flurbiprofen, on epithelial cell proliferation was assessed using a stathmokinetic technique. The epithelia examined were those of the jejunal crypts, the colonic crypts and that of dimethylhydrazine-induced adenocarcinomas of rat colon. The influence of the two prostaglandin analogues, and of flurbiprofen, on the growth of a human colorectal tumour propagated as xenografts in immune-deprived mice was also assessed. The PG E2 analogue transiently inhibited xenograft growth, but was without effect on the mitotic rate in the rat tissues. The PG F2 alpha analogue was also found to inhibit xenograft growth but, unlike the PG E2 analogue, it was found to be a strong inhibitor of cell proliferation in rat colonic tumours, and an accelerator of proliferation in jejunal-crypt cells. The only statistically significant effect of flurbiprofen was to accelerate cell division in the rat colonic tumours.

Urinary prostaglandin excretion in pregnancy: the effect of dietary sodium restriction.

Science.gov (United States)

Delemarre, F M; Thomas, C M; van den Berg, R J; Jongsma, H W; Steegers, E A

2000-10-01

Dietary sodium restriction results in activation of the renin-angiotensin-aldosterone-system. In the non-pregnant situation renin release in response to a low sodium diet is mediated by prostaglandins. We studied the effect of dietary sodium restriction on urinary prostaglandin metabolism in pregnancy. In a randomized, longitudinal study the excretion of urinary metabolites of prostacyclin (6-keto-PGF(1 alpha)and 2,3-dinor-6-keto-PGF(1 alpha)) and thromboxane A(2)(TxB(2)and 2,3-dinor-TxB(2)) was determined throughout pregnancy and post partum in 12 women on a low sodium diet and in 12 controls. In pregnancy the excretion of all urinary prostaglandins is increased. The 6-keto-PGF(1 alpha)/ TxB(2)-ratio as well as the 2, 3-dinor-6-keto-PGF(1 alpha)/ 2,3-dinor-TxB(2)-ratio did not significantly change in pregnancy. CONCLUISION Prostacyclin and thromboxane do not seem to play an important role in sodium balance during pregnancy. Copyright 2000 Harcourt Publishers Ltd.

Mechanistic Scrutiny Identifies a Kinetic Role for Cytochrome b5 Regulation of Human Cytochrome P450c17 (CYP17A1, P450 17A1.

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Alexandr N Simonov

Full Text Available Cytochrome P450c17 (P450 17A1, CYP17A1 is a critical enzyme in the synthesis of androgens and is now a target enzyme for the treatment of prostate cancer. Cytochrome P450c17 can exhibit either one or two physiological enzymatic activities differentially regulated by cytochrome b5. How this is achieved remains unknown. Here, comprehensive in silico, in vivo and in vitro analyses were undertaken. Fluorescence Resonance Energy Transfer analysis showed close interactions within living cells between cytochrome P450c17 and cytochrome b5. In silico modeling identified the sites of interaction and confirmed that E48 and E49 residues in cytochrome b5 are essential for activity. Quartz crystal microbalance studies identified specific protein-protein interactions in a lipid membrane. Voltammetric analysis revealed that the wild type cytochrome b5, but not a mutated, E48G/E49G cyt b5, altered the kinetics of electron transfer between the electrode and the P450c17. We conclude that cytochrome b5 can influence the electronic conductivity of cytochrome P450c17 via allosteric, protein-protein interactions.

Intravenous infusion of prostaglandin E2 for management of premature rupture of membranes.

Science.gov (United States)

Thiery, M; Parewijck, W; Martens, G

1982-01-01

In term with premature rupture of the membranes (PROM) and an unripe cervix who have no contraindications for prostaglandin (PG) administration and vaginal delivery, intravenous (I.V.) infusion of titrated PGE2 is highly effective. In healthy gravidas with dito fetus this treatment appeared perinatally safe and was well tolerated by the mother. To enhance its safety margin and procedure must be conducted under toco-cardiographic control.

Additive intraocular pressure-lowering effect of dorzolamide 1%/timolol 0.5% fixed combination on prostaglandin monotherapy in patients with normal tension glaucoma

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Mizoguchi T

2011-10-01

Full Text Available Takanori Mizoguchi1, Mineo Ozaki2, Harumi Wakiyama1,3, Nobuchika Ogino11Mizoguchi Eye Clinic, Sasebo, 2Ozaki Eye Clinic and Dept of Opthalmology, Faculty of Medicine, University of Miyazaki, Miyazaki, 3The Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, JapanPurpose: To evaluate the intraocular pressure (IOP-lowering effect of adding dorzolamide 1.0%/timolol 0.5% fixed combination (DTFC to prostaglandin analogs (PGAs as monotherapy in patients with normal tension glaucoma.Methods: A prospective, clinical, case-controlled study of patients with normal tension glaucoma. Patients had been on a once-daily night dose of prostaglandins (PGs as monotherapy and then received DTFC added to PGs for 8 weeks. The IOP was measured at 9 am, week 0 (baseline, week 4, and week 8.Results: The baseline IOP of 40 patients who had previously been treated by prostaglandin monotherapy was 15.6 ± 2.0 mmHg at baseline. The IOPs at 4 and 8 weeks after adding DTFC to PGs were 13.5 ± 2.1 mmHg and 13.7 ± 2.2 mmHg, respectively. Significant decrease of the IOP was observed at each time point of measurement as compared with the baseline IOP before adding DTFC (P = 0.01. The percent IOP reduction from the baseline IOP at week 4 and week 8 was 13.5% ± 12.3% and 11.7% ± 13.1%, respectively. The percentage of patients who achieved 10% or more IOP reduction from the baseline IOP at week 8 was 62.5%. The baseline IOP was significantly correlated with the percent IOP reduction at week 8 (P = 0.03, r = 0.34.Conclusion: DTFC therapy added to PGAs as glaucoma monotherapy is effective in patients with normal tension glaucoma.Keywords: IOP-lowering effect, prostaglandin, dorzolamide 1%/timolol 0.5% fixed combination, fixed combination, normal tension glaucoma

A urinary metabolite of {Delta}{sup 1}-tetrahydrocannabinol. The first synthesis of 4``-hydroxy-{Delta}{sup 1}-tetrahydrocannabinol-7-oic acid labelled with deuterium

Energy Technology Data Exchange (ETDEWEB)

Szirmai, Maria; Odqvist, Helena [Uppsala Univ. (Sweden). Dept. of Pharmacognosy; Halldin, M.M. [Karolinska Inst., Stockholm (Sweden). Dept. of Pharmacology

1996-04-01

The first synthesis of 4``-hydroxy-{Delta}-{sup 1}-THC-7-oic acid, one of the three major metabolites of {Delta}{sup 1}-THC identified in human urine is discussed. Methyl 4-(3,5-dihydroxyphenyl)butanoate was prepared from 3,5-diydroxybenzoic acid in an overall yield of 15% was condensed with a terpene synthon under acidic conditions followed by hydrolysis and conversion of the 4``-carboxylic acid function to the corresponding methyl ketone using methyllithium. Reduction with NaBH{sub 4} afforded the secondary alcohol in the side-chain. Acetylation and removal of the 1,3-dithiane masking group gave the aldehyde in C-7-position which was further oxidized using NaClO{sub 2} followed by deacetylation to give the desired metabolite. The same procedure may be used for the synthesis of unlabelled 4``-hydroxy-{Delta}{sup 1}-THC-7-oic acid. (author).

Plasma 8-iso-Prostaglandin F2α concentrations and outcomes after acute intracerebral hemorrhage.

Science.gov (United States)

Du, Quan; Yu, Wen-Hua; Dong, Xiao-Qiao; Yang, Ding-Bo; Shen, Yong-Feng; Wang, Hao; Jiang, Li; Du, Yuan-Feng; Zhang, Zu-Yong; Zhu, Qiang; Che, Zhi-Hao; Liu, Qun-Jie

2014-11-01

Higher plasma 8-iso-Prostaglandin F2α concentrations have been associated with poor outcome of severe traumatic brain injury. We further investigated the relationships between plasma 8-iso-Prostaglandin F2α concentrations and clinical outcomes in patients with acute intracerebral hemorrhage. Plasma 8-iso-Prostaglandin F2α concentrations of 128 consecutive patients and 128 sex- and gender-matched healthy subjects were measured by enzyme-linked immunosorbent assay. We assessed their relationships with disease severity and clinical outcomes including 1-week mortality, 6-month mortality and unfavorable outcome (modified Rankin Scale score>2). Plasma 8-iso-Prostaglandin F2α concentrations were substantially higher in patients than in healthy controls. Plasma 8-iso-Prostaglandin F2α concentrations were positively associated with National Institutes of Health Stroke Scale (NIHSS) scores and hematoma volume using a multivariate linear regression. It emerged as an independent predictor for clinical outcomes of patients using a forward stepwise logistic regression. ROC curves identified the predictive values of plasma 8-iso-Prostaglandin F2α concentrations, and found its predictive value was similar to NIHSS scores and hematoma volumes. However, it just numerically added the predictive values of NIHSS score and hematoma volume. Increased plasma 8-iso-Prostaglandin F2α concentrations are associated with disease severity and clinical outcome after acute intracerebral hemorrhage. Copyright © 2014 Elsevier B.V. All rights reserved.

Prostaglandin E2 and the protein kinase A pathway mediate arachidonic acid induction of c-fos in human prostate cancer cells

Science.gov (United States)

Chen, Y.; Hughes-Fulford, M.

2000-01-01

Arachidonic acid (AA) is the precursor for prostaglandin E2 (PGE2) synthesis and increases growth of prostate cancer cells. To further elucidate the mechanisms involved in AA-induced prostate cell growth, induction of c-fos expression by AA was investigated in a human prostate cancer cell line, PC-3. c-fos mRNA was induced shortly after addition of AA, along with a remarkable increase in PGE2 production. c-fos expression and PGE2 production induced by AA was blocked by a cyclo-oxygenase inhibitor, flurbiprofen, suggesting that PGE2 mediated c-fos induction. Protein kinase A (PKA) inhibitor H-89 abolished induction of c-fos expression by AA, and partially inhibited PGE2 production. Protein kinase C (PKC) inhibitor GF109203X had no significant effect on c-fos expression or PGE2 production. Expression of prostaglandin (EP) receptors, which mediate signal transduction from PGE2 to the cells, was examined by reverse transcription polymerase chain reaction in several human prostate cell lines. EP4 and EP2, which are coupled to the PKA signalling pathway, were expressed in all cells tested. Expression of EP1, which activates the PKC pathway, was not detected. The current study showed that induction of the immediate early gene c-fos by AA is mediated by PGE2, which activates the PKA pathway via the EP2/4 receptor in the PC-3 cells.

Prostaglandin E(2) stimulates glutamate receptor-dependent astrocyte neuromodulation in cultured hippocampal cells.

Science.gov (United States)

Sanzgiri, R P; Araque, A; Haydon, P G

1999-11-05

Recent Ca(2+) imaging studies in cell culture and in situ have shown that Ca(2+) elevations in astrocytes stimulate glutamate release and increase neuronal Ca(2+) levels, and that this astrocyte-neuron signaling can be stimulated by prostaglandin E(2) (PGE(2)). We investigated the electrophysiological consequences of the PGE(2)-mediated astrocyte-neuron signaling using whole-cell recordings on cultured rat hippocampal cells. Focal application of PGE(2) to astrocytes evoked a Ca(2+) elevation in the stimulated cell by mobilizing internal Ca(2+) stores, which further propagated as a Ca(2+) wave to neighboring astrocytes. Whole-cell recordings from neurons revealed that PGE(2) evoked a slow inward current in neurons adjacent to astrocytes. This neuronal response required the presence of an astrocyte Ca(2+) wave and was mediated through both N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors. Taken together with previous studies, these data demonstrate that PGE(2)-evoked Ca(2+) elevations in astrocyte cause the release of glutamate which activates neuronal ionotropic receptors. Copyright 1999 John Wiley & Sons, Inc.

Prostaglandin E2 Regulates Liver versus Pancreas Cell Fate Decisions and Endodermal Outgrowth

Science.gov (United States)

Nissim, Sahar; Sherwood, Richard I.; Wucherpfennig, Julia; Saunders, Diane; Harris, James M.; Esain, Virginie; Carroll, Kelli J.; Frechette, Gregory M.; Kim, Andrew J.; Hwang, Katie L.; Cutting, Claire C.; Elledge, Susanna; North, Trista E.; Goessling, Wolfram

2014-01-01

SUMMARY The liver and pancreas arise from common endodermal progenitors. How these distinct cell fates are specified is poorly understood. Here, we describe prostaglandin E2 (PGE2) as a regulator of endodermal fate specification during development. Modulating PGE2 activity has opposing effects on liver-versus-pancreas specification in zebrafish embryos as well as mouse endodermal progenitors. The PGE2 synthetic enzyme cox2a and receptor ep2a are patterned such that cells closest to PGE2 synthesis acquire a liver fate whereas more distant cells acquire a pancreas fate. PGE2 interacts with the bmp2b pathway to regulate fate specification. At later stages of development, PGE2 acting via the ep4a receptor promotes outgrowth of both the liver and pancreas. PGE2 remains important for adult organ growth, as it modulates liver regeneration. This work provides in vivo evidence that PGE2 may act as a morphogen to regulate cell fate decisions and outgrowth of the embryonic endodermal anlagen. PMID:24530296

A novel selective prostaglandin E2 synthesis inhibitor relieves pyrexia and arthritis in Guinea pigs inflammatory models

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Ryusuke Sugita

2016-02-01

Full Text Available Prostaglandin E2 (PGE2, one of the terminal products in the cyclooxygenase pathway, plays an important role in various inflammatory responses. To determine whether selective inhibition of PGE2 may relieve these inflammatory symptoms, we synthesized a selective PGE2 synthesis inhibitor, compound A [1-(6-fluoro-5,7-dimethyl-1,3-benzothiazol-2-yl-N-[(1S,2R-2-(hydroxymethylcyclohexyl]piperidine-4-carboxamide], then investigated the effects on pyrexia, arthritis and inflammatory pain in guinea pigs. In LPS-stimulated guinea pig macrophages, compound A selectively inhibited inducible PGE2 biosynthesis in a dose-dependent manner whereas enhanced the formation of thromboxane B2 (TXB2. Compound A suppressed yeast-evoked PGE2 production selectively and enhanced the production of TXB2 and 6-keto PGF1α in vivo. In addition, compound A relieved yeast-induced pyrexia and also suppressed paw swelling in an adjuvant-induced arthritis model. The effect on gastrointestinal (GI ulcer formation was also evaluated and compound A showed a lower GI adverse effect than indomethacin. However, compound A failed to relieve yeast-induced thermal hyperalgesia. These results suggest that selective inhibition of PGE2 synthesis may have anti-pyretic and anti-inflammatory properties without GI side effect, but lack the analgesic efficacy.

Carvacrol as the inhibitor of cyclooxygenase-1 and -2, the key enzymes of prostaglandin biosynthesis: in vitro assays

Czech Academy of Sciences Publication Activity Database

Maršík, Petr; Landa, Přemysl; Přibylová, Marie; Vaněk, Tomáš; Kokoška, L.

2006-01-01

Roč. 72, č. 11 (2006), s. 1010 ISSN 0032-0943. [Annual Congress on Medicinal Plant Research. 29.08.2006-02.09.2006, Helsinki] R&D Projects: GA MŠk(CZ) 1P04OC926.001 Institutional research plan: CEZ:AV0Z40550506 Keywords : carvacrol * cyclooxygenase-1 and -2 * prostaglandins Subject RIV: CE - Biochemistry

The roles of MCP-1 and protein kinase C delta activation in human eosinophilic leukemia EoL-1 cells.

Science.gov (United States)

Lee, Ji-Sook; Yang, Eun Ju; Kim, In Sik

2009-12-01

Idiopathic hypereosinophilc syndrome is a disorder associated with clonally eosinophilic proliferation. The importance of FIP1-like-1-platelet-derived growth factor receptor-alpha (FIP1L1-PDGFRA) in the pathogenesis and classification of HES has been recently reported. In this study, we investigated the contribution of monocyte chemoattractant protein-1 (MCP-1)/CCL2 to chemotactic activity and protein kinase C delta (PKC delta in the human eosinophilic leukemia cell line EoL-1. These cells express CCR2 protein among the CC chemokine receptors (CCR1-5). MCP-1 induces strong migration of EoL-1 cells and the chemotaxis signal in response to MCP-1 involves a G(i)/G(o) protein, phospholipase C (PLC), PKC delta, p38 MAPK and NF-kappaB. MCP-1 activates p38 MAPK via G(i)/G(o) protein, PLC and PKC delta cascade. MCP-1 also induces NF-kappaB translocation and the activation is inhibited by PKC delta activation. The increase in the basal expression and activity of PKC delta in EoL-1 cells, compared to normal eosinophils, inhibits apoptosis in EoL-1 cells. Anti-apoptotic mechanism of PKC delta is related to inhibition of caspase 3 and caspase 9, but not to FIP1L1-PDGFRA. PKC delta functions as an anti-apoptotic molecule, and is involved in EoL-1 cell movement stimulated by MCP-1. This study contributes to an understanding of MCP-1 in eosinophil biology and pathogenic mechanism of eosinophilic disorders.

Inhibition of prostaglandin synthesis after metabolism of menadione by cultured porcine endothelial cells

International Nuclear Information System (INIS)

Barchowsky, A.; Tabrizi, K.; Kent, R.S.; Whorton, A.R.

1989-01-01

We have examined the effects of menadione on porcine aortic endothelial cell prostaglandin synthesis. Addition of 1-20 microM menadione caused a dose- and time-dependent inhibition of stimulated prostaglandin synthesis with an IC50 of 5 microM at 15 min. Concentrations greater than 100 microM menadione were necessary to increase 51 Cr release from prelabeled cells. Recovery of enzyme inactivated by menadione required a 6-h incubation in 1% serum. In a microsomal preparation, menadione was shown to have no direct effect on conversion of arachidonic acid to prostaglandins. In intact cells menadione caused only a 40% inhibition of the conversion of PGH2 to prostacyclin. Enzymes involved in the incorporation and the release of arachidonic acid were not affected by menadione (20 microM, 15 min). Menadione undergoes oxidation/reduction reactions in intact cells leading to partial reduction of oxygen-forming, reactive oxygen species. In our cells menadione was found to increase KCN-resistant oxygen consumption. Further, an increased accumulation of H 2 O 2 was observed with a time course consistent with menadione-induced inhibition of prostaglandin synthesis. We conclude that menadione at sublethal doses caused inhibition of prostaglandin synthesis. The mechanism involves inactivation of PGH2 synthase by a reactive species resulting from metabolism of menadione by endothelial cells

Prostaglandin-associated periorbitopathy in latanoprost users

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Nakakura S

2014-12-01

Full Text Available Shunsuke Nakakura,1 Minamai Yamamoto,1 Etsuko Terao,1 Nozomi Nagatomi,1 Naoko Matsuo,1 Yausko Fujisawa,1 Yuki Fujio,1 Hitoshi Tabuchi,1 Yoshiaki Kiuchi2 1Department of Ophthalmology, Saneikai Tsukazaki Hospital, Himeji, Japan; 2Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan Purpose: We investigated the incidence of prostaglandin-associated periorbitopathy (PAP in subjects with glaucoma treated with latanoprost ophthalmic solution.Subjects and methods: One eye and the forehead in 22 subjects were evaluated. All patients had used latanoprost for more than 1 year (range, 12 to 45 months; mean, 26.0 months and were prostaglandin F2α analogue treatment-naïve. Digital photographs of the subjects obtained before latanoprost therapy and at the last examination were compared retrospectively. Four signs of PAP (deepening of the upper eyelid sulcus (DUES, upper eyelid ptosis, flattening of the lower eyelid bags, and inferior scleral show and supplemental side effects around the eyelids (eyelash growth, poliosis, and eyelid pigmentation were judged to be negative or positive by three independent observers. If the observers unanimously rated a sign as positive, the result was defined as positive.Results: Twelve subjects (54.5% had no apparent signs. Three subjects were judged to have DUES (13.6%, and two subjects each were judged to have flattening of the lower eyelid bags and eyelid pigmentation (9.0%. The other signs were judged as positive in only one subject each, respectively (4.5%. A univariate logistic regression analysis showed no significant associations between any of the signs and age, sex, or the duration of therapy.Conclusion: Latanoprost induced DUES, upper eyelid ptosis, flattening of the lower eyelid bags, inferior scleral show, and supplemental side effects around the eyelids; however, the rates of such occurrence might be relatively low. Keywords: glaucoma

a randomised controlled trial oftwo prostaglandin regitnens

African Journals Online (AJOL)

Design. A prospective randomised controlled trial. Setting. Department of Obstetrics and Gynae- ... hours after the original administration of either prostaglandin regimen. If abortion had not taken place 36 .... Tygerberg Hospital for permission to publish, and Upjohn. (Pry) Ltd for supplying the Prepidil gel used in the study. 1.

Multiple roles of the prostaglandin D2 signaling pathway in reproduction.

Science.gov (United States)

Rossitto, Moïra; Ujjan, Safdar; Poulat, Francis; Boizet-Bonhoure, Brigitte

2015-01-01

Prostaglandins signaling molecules are involved in numerous physiological processes. They are produced by several enzyme-limited reactions upon fatty acids, which are catalyzed by two cyclooxygenases and prostaglandin synthases. In particular, the prostaglandins E2 (PGE2), D2 (PGD2), and F2 (PGF2 α) have been shown to be involved in female reproductive mechanisms. Furthermore, widespread expression of lipocalin- and hematopoietic-PGD2 synthases in the male reproductive tract supports the purported roles of PGD2 in the development of both embryonic and adult testes, sperm maturation, and spermatogenesis. In this review, we summarize the putative roles of PGD2 signaling and the roles of both PGD2 synthases in testicular formation and function. We review the data reporting the involvement of PGD2 signaling in the differentiation of Sertoli and germ cells of the embryonic testis. Furthermore, we discuss the roles of lipocalin-PGD2 synthase in steroidogenesis and spermatogenesis, in terms of lipid molecule transport and PGD2 production. Finally, we discuss the hypothesis that PGD2 signaling may be affected in certain reproductive diseases, such as infertility, cryptorchidism, and testicular cancer. © 2015 Society for Reproduction and Fertility.

delta-EF1 is a negative regulator of Ihh in the developing growth plate.

Science.gov (United States)

Bellon, Ellen; Luyten, Frank P; Tylzanowski, Przemko

2009-11-30

Indian hedgehog (Ihh) regulates proliferation and differentiation of chondrocytes in the growth plate. Although the biology of Ihh is currently well documented, its transcriptional regulation is poorly understood. delta-EF1 is a two-handed zinc finger/homeodomain transcriptional repressor. Targeted inactivation of mouse delta-EF1 leads to skeletal abnormalities including disorganized growth plates, shortening of long bones, and joint fusions, which are reminiscent of defects associated with deregulation of Ihh signaling. Here, we show that the absence of delta-EF1 results in delayed hypertrophic differentiation of chondrocytes and increased cell proliferation in the growth plate. Further, we demonstrate that delta-EF1 binds to the putative regulatory elements in intron 1 of Ihh in vitro and in vivo, resulting in down-regulation of Ihh expression. Finally, we show that delta-EF1 haploinsufficiency leads to a postnatal increase in trabecular bone mass associated with enhanced Ihh expression. In summary, we have identified delta-EF1 as an in vivo negative regulator of Ihh expression in the growth plate.

16,16-dimethyl prostaglandin E2 increases survival of murine intestinal stem cells when given before photon radiation

International Nuclear Information System (INIS)

Hanson, W.R.; Thomas, C.

1983-01-01

A variety of prostaglandins (PG) protect the gastric and intestinal mucosa when given before damaging agents as absolute ethanol, acidified taurocholate, boiling water, or nonsteroidal anti-inflammatory agents (NSAI). A synthetic prostaglandin, 16,16-dimethyl PGE 2 , shown to be cytoprotective at physiologic levels to the above agents was given to mice 1 h before or 15 min after 137 Cs gamma(γ) whole-body irradiation. The survival of intestinal stem cells measured by their ability to form in situ colonies of regenerating epithelium was increased stem cells measured by their ability to form in situ colonies of regenerating epithelium was increased when 16,16-dimethyl PGE 2 was given before but not after 137 Cs γ irradiation. The maximum degree of 16,16-dimethyl PGE 2 -induced radioprotection was seen when the drug was given 1 h before irradiation. No radioprotection was seen when the interval between drug and irradiation was 3 h or longer. When the time between 16,16-dimethyl PGE 2 and irradiation was kept at 1 h, the degree of radioprotection was dependent on the PG drug dose. There was a steep rise in the number of surviving cells at low doses of PG. These results imply that tumors which secrete PGE 2 may in part be protected from the lethal effects of ionizing photon radiation

Influence of endogenous pyrogen on the cerebral prostaglandin-synthetase system.

Science.gov (United States)

Ziel, R; Krupp, P

1976-11-15

The biotransformation of arachidonic acid to prostaglandins in vitro is specifically augmented by endogenous pyrogen to a degree depending on the concentration applied, providing that the microsomal fraction of the cerebral cortex is used as prostaglandin-synthetase system. This effect is inhibited by non-steroidal anti-inflammatory agents. These findings are compatible with the hypothesis that prostaglandins might act as mediators of the febrile reaction induced by endogenous pyrogen.

The introduction of tritium label into natural and modified prostaglandins

International Nuclear Information System (INIS)

Shevchenko, V.P.; Bezuglov, V.V.; Nagayev, I.Y.; Myasoedov, N.F.

1989-01-01

Studies on the role of the nature of both heterogeneous catalysts and the solvent on the reduction selectively of 5,6-double bonds showed that the largest yield could be obtained by using the Lindlar catalyst and ethyl acetate. The use of different isotopes of hydrogen in the protium-deuterium-tritium series markedly decreased the hydrogenation reaction rate, but the selectivity of the process practically remained unaltered. Homogeneous catalysts were also used in the production of natural tritium-labelled prostaglandins and of their fluorine and deoxy analogues. The label was introduced by selective hydrogenation in the presence of (Ph 3 P) 3 RhCl and dioxane as solvent. Different ways have been studied of tritium-label introduction into prostaglandins modified at the carboxyl group. The synthesis of similar preparations was performed either by selective dehalogenation in the presence of heterogeneous catalysts treated with quinoline or triethylamine, or by condensation of prostaglandins at the carboxyl group by tritium-labelled amino acid. (author). 4 refs.; 1 fig

Human urinary excretion profile after smoking and oral administration of [14C]delta 1-tetrahydrocannabinol

International Nuclear Information System (INIS)

Johansson, E.; Gillespie, H.K.; Halldin, M.M.

1990-01-01

The urinary excretion profiles of delta 1-tetrahydrocannabinol (delta 1-THC) metabolites have been evaluated in two chronic and two naive marijuana users after smoking and oral administration of [ 14 C]delta 1-THC. Urine was collected for five days after each administration route and analyzed for total delta 1-THC metabolites by radioactivity determination, for delta 1-THC-7-oic acid by high-performance liquid chromatography, and for cross-reacting cannabinoids by the EMIT d.a.u. cannabinoid assay. The average urinary excretion half-life of 14 C-labeled delta 1-THC metabolites was calculated to be 18.2 +/- 4.9 h (+/- SD). The excretion profiles of delta 1-THC-7-oic acid and EMIT readings were similar to the excretion profile of 14 C-labeled metabolites in the naive users. However, in the chronic users the excretion profiles of delta 1-THC-7-oic acid and EMIT readings did not resemble the radioactive excretion due to the heavy influence from previous Cannabis use. Between 8-14% of the radioactive dose was recovered in the urine in both user groups after oral administration. Lower urinary recovery was obtained both in the chronic and naive users after smoking--5 and 2%, respectively

GÊNESE E MORFODINÂMICA DAS BARREIRAS ARENOSAS NO FLANCO NORTE DO DELTA DO RIO PARAÍBA DO SUL (RJ

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Sérgio Cadena de Vasconcelos

2016-09-01

Full Text Available A formação de barreiras arenosas é comum em deltas dominados por ondas, associada ao expressivo aporte sedimentar dos rios. Nesses ambientes é possível o desenvolvimento de barreiras do tipo spit, ilha-barreira e sistema barreira-laguna. Historicamente essas feições foram associadas ao desenvolvimento assimétrico dos deltas e ao papel da deriva litorânea. Nesse sentido, o objetivo do presente trabalho é investigar a gênese e a morfodinâmica das barreiras arenosas que ocorrem no flanco norte do delta do rio Paraíba do Sul, considerando aspectos relacionadas às porções submarina e emersa do delta. Foram calculados dados de ondas e sentido de transporte litorâneo; coletados perfis batimétricos junto à costa, perfis topográficos na barreira emersa e mapeamento em planta a partir de sensoriamento remoto sobre imagens de alta resolução espacial. Foi possível identificar, em escala de detalhe, estágios de desenvolvimento e evolução associados à formação de barras submarinas na frente deltaica; a emersão de barreira arenosa na forma de spit; a progradação lateral a partir das correntes de deriva litorânea; e a conexão do spit ao continente, passando a isolar um sistema lagunar. Este processo foi considerado como um dos mecanismos de gênese de cristas de praia que formam a planície deltaica ao norte do rio Paraíba do Sul. Recentemente, tais feições e processos têm sido interpretados como decorrente de um padrão de ondas assimétricas que chegam à linha de costa com ângulo de obliquidade elevado, produzindo as feições de instabilidade e a assimetria do delta.

Doubly truncated FosB isoform (Delta2DeltaFosB) induces osteosclerosis in transgenic mice and modulates expression and phosphorylation of Smads in osteoblasts independent of intrinsic AP-1 activity

DEFF Research Database (Denmark)

Sabatakos, George; Rowe, Glenn C; Kveiborg, Marie

2008-01-01

DeltaFosB and a further truncated isoform (Delta2DeltaFosB) that lacks known transactivation domains but, like DeltaFosB, induces increased expression of osteoblast marker genes. MATERIALS AND METHODS: To test Delta2DeltaFosB's ability to induce bone formation in vivo, we generated transgenic mice......6 expression. CONCLUSIONS: DeltaFosB's AP-1 transactivating function is not needed to induce increased bone formation, and Delta2DeltaFosB may act, at least in part, by increasing Smad1 expression, phosphorylation, and translocation to the nucleus....

Inhibition of prostaglandin synthesis after metabolism of menadione by cultured porcine endothelial cells.

OpenAIRE

Barchowsky, A; Tabrizi, K; Kent, R S; Whorton, A R

1989-01-01

We have examined the effects of menadione on porcine aortic endothelial cell prostaglandin synthesis. Addition of 1-20 microM menadione caused a dose- and time-dependent inhibition of stimulated prostaglandin synthesis with an IC50 of 5 microM at 15 min. Concentrations greater than 100 microM menadione were necessary to increase 51Cr release from prelabeled cells. Recovery of enzyme inactivated by menadione required a 6-h incubation in 1% serum. In a microsomal preparation, menadione was show...

Effects of indomethacin, NS-398 (a selective prostaglandin H synthase-2 inhibitor) and protein synthesis inhibitors on prostaglandin production by the guinea-pig placenta.

Science.gov (United States)

Aitken, H; Poyser, N L

2001-01-01

The outputs of PGF(2 alpha), PGE2 and 6-keto-PGF(1 alpha)were similar from the day 22 guinea-pig placenta and sub-placenta in culture, except for PGE2 output from the sub-placenta which was lower. Between days 22 and 29 of pregnancy, the outputs of PGF(2 alpha), PGE2 and 6-keto-PGF(1 alpha)during the initial 2 h culture period increased 6.9-, 1.1- and 3.2-fold, respectively, from the placenta, and 2.1-, 1.4- and 2.2-fold, respectively, from the sub-placenta. Therefore, there was a relatively specific increase in PGF(2 alpha)production by the guinea-pig placenta between days 22 and 29 of pregnancy. The output of PGFM from the cultured placenta also increased between days 22 and 29, indicating that the increase in PGF(2 alpha)output was due to increased synthesis rather than to decreased metabolism. By comparing the amounts of prostaglandins produced by tissue homogenates during a 1 h incubation period, it appears that there is approximately a 2-fold increase in the amount of prostaglandin H synthase (PGHS) present in the guinea-pig placenta between days 22 and 29. NS-398 (a specific inhibitor of PGHS-2) and indomethacin (an inhibitor of both PGHS-1 and PGHS-2) both inhibited prostaglandin production by homogenates of day 22 and day 29 placenta. Indomethacin was more effective than NS-398, except for their actions on PGF(2 alpha)production by the day 29 placenta where indomethacin and NS-398 were equiactive. Indomethacin and NS-398 were both very effective at inhibiting the outputs of PGF(2 alpha), PGE2 and 6-keto-PGF(1 alpha)from the day 22 and day 29 placenta and sub-placenta in culture, indicating that prostaglandin production by the guinea-pig placenta and sub-placenta in culture is largely dependent upon the activity of PGHS-2. The high production of PGF(2 alpha)by the day 29 placenta is not dependent on the continual synthesis of fresh protein(s), as inhibitors of protein synthesis did not reduce PGF(2 alpha)output from the day 29 guinea-pig placenta in culture

Firocoxib on aqueous humor prostaglandin E 2 levels for controlling experimentally-induced breakdown of blood-aqueous barrier in healthy and Toxoplasma gondii -seropositive cats

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Deise Cristine Schroder

2016-06-01

Full Text Available ABSTRACT: This study aimed to evaluate the effects of firocoxib for controlling experimentally-induced breakdown of the blood-aqueous barrier in healthy and Toxoplasma gondii -seropositive cats. Thirty two cats with no ocular abnormalities were used. Groups (n=8/each were formed with healthy cats that received 5mg g-1 of oral firocoxib (FH or no treatment (CH on day 0; seropositive cats for anti -T. gondii specific immunoglobulin G (IgG were grouped (n=8/each and treated in a similar fashion (FT and CT. On day 1, cats of all groups received the same treatment protocol, and 1h later, aqueocentesis was performed under general anesthesia (M0. Following 1h, the same procedure was repeated (M1. Quantitation of aqueous humor total protein and prostaglandin E2 (PGE2 were determined. Aqueous samples of seropositive cats were tested for anti- T. gondii specific IgG. In M0, aqueous samples of CT showed a significantly higher concentration of PGE2 in comparison with other groups (P<0.05. In all groups, PGE2 concentration increased significantly from M0 to M1 (P=0.001. PGE2 values did not change significantly between groups in M1 (P=0.17. Anti- T. gondii specific IgG were reported only in samples of M1, and aqueous titers did not change significantly between FT and CT (P=0.11. Although we have observed that aqueous humor PGE2 levels were significantly higher in cats of CT group during M0, such increase was not able to break the blood-aqueous barrier and cause anterior uveitis. Firocoxib did not prevent intraocular inflammation after aqueocentesis, in healthy and toxoplasmosis-seropositive cats.

Human interleukin 1β (IL-1β), a more powerful inducer of bone demineralization than interleukin 1α (IL-1α), parathyroid hormone (PTH) or prostaglandin E2 (PGE2) in vitro

International Nuclear Information System (INIS)

Chin, R.C.; Hodges, Y.C.; Allison, A.C.

1986-01-01

Effects of human IL-1α and IL-1β, prepared by recombinant DNA technology on cultures of rat fetal long bones, prelabelled with 45 Ca were studied. IL-1β was found to be the most powerful inducer of bone calcium loss so far known. Maximal activity (2.5 times the control rate of calcium loss) was induced by IL-1β at concentrations between 1 x 10 -10 M to 6 x 10 -12 M. With IL-1α maximal activity (1.5 times the control rate of calcium loss) was obtained at 6 x 10 -10 M. With bovine PTH (1-34) maximal activity (1.8 times the control rate of calcium loss) was obtained at 1 x 10 -8 M. With PGE 2 maximal activity (1.6 times the control rate of calcium loss) was obtained at 1 x 10 -7 M. The calcium loss induced by IL-1β was inhibited in the presence of 1 x 10 -7 M indomethacin, 5 x 10 -5 M naproxen or ketorolac, or 5 x 10 -6 M cyclohexamide. These findings suggest that protein synthesis and prostaglandin formation are required to mediate bone demineralization induced by IL-1β

Vitamin-E reduces the oxidative damage on delta-aminolevulinic dehydratase induced by lead intoxication in rat erythrocytes.

Science.gov (United States)

Rendón-Ramirez, A; Cerbón-Solórzano, J; Maldonado-Vega, M; Quintanar-Escorza, M A; Calderón-Salinas, J V

2007-09-01

Lead intoxication induces oxidative damage on lipids and proteins. In the present paper we study in vivo and in vitro the antioxidant effect of vitamin-E and trolox, on the oxidative effects of lead intoxication in rat erythrocytes. Vitamin-E simultaneously administered to erythrocytes treated with lead was capable to prevent the inhibition of delta-aminolevulinic dehydratase activity and lipid oxidation. Partial but important protective effects were found when vitamin-E was administered either after or before lead exposure in rats. In vitro, the antioxidant trolox protected delta-ALA-D activity against damage induced by lead or menadione. These results indicate that vitamin-E could be useful in order to protect membrane-lipids and, notably, to prevent protein oxidation produced by lead intoxication.

Image Fusion Based on the \\({\\Delta ^{ - 1}} - T{V_0}\\ Energy Function

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Qiwei Xie

2014-11-01

Full Text Available This article proposes a \\({\\Delta^{-1}}-T{V_0}\\ energy function to fuse a multi-spectral image with a panchromatic image. The proposed energy function consists of two components, a \\(TV_0\\ component and a \\(\\Delta^{-1}\\ component. The \\(TV_0\\ term uses the sparse priority to increase the detailed spatial information; while the \\({\\Delta ^{ - 1}}\\ term removes the block effect of the multi-spectral image. Furthermore, as the proposed energy function is non-convex, we also adopt an alternative minimization algorithm and the \\(L_0\\ gradient minimization to solve it. Experimental results demonstrate the improved performance of the proposed method over existing methods.

Design of group IIA secreted/synovial phospholipase A(2 inhibitors: an oxadiazolone derivative suppresses chondrocyte prostaglandin E(2 secretion.

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Jean-Edouard Ombetta

Full Text Available Group IIA secreted/synovial phospholipase A(2 (GIIAPLA(2 is an enzyme involved in the synthesis of eicosanoids such as prostaglandin E(2 (PGE(2, the main eicosanoid contributing to pain and inflammation in rheumatic diseases. We designed, by molecular modeling, 7 novel analogs of 3-{4-[5(indol-1-ylpentoxy]benzyl}-4H-1,2,4-oxadiazol-5-one, denoted C1, an inhibitor of the GIIAPLA(2 enzyme. We report the results of molecular dynamics studies of the complexes between these derivatives and GIIAPLA(2, along with their chemical synthesis and results from PLA(2 inhibition tests. Modeling predicted some derivatives to display greater GIIAPLA(2 affinities than did C1, and such predictions were confirmed by in vitro PLA(2 enzymatic tests. Compound C8, endowed with the most favorable energy balance, was shown experimentally to be the strongest GIIAPLA(2 inhibitor. Moreover, it displayed an anti-inflammatory activity on rabbit articular chondrocytes, as shown by its capacity to inhibit IL-1beta-stimulated PGE(2 secretion in these cells. Interestingly, it did not modify the COX-1 to COX-2 ratio. C8 is therefore a potential candidate for anti-inflammatory therapy in joints.

Prostaglandin E2 stimulates normal bronchial epithelial cell growth through induction of c-Jun and PDK1, a kinase implicated in oncogenesis.

Science.gov (United States)

Fan, Yu; Wang, Ye; Wang, Ke

2015-12-18

Cyclooxygenase-2-derived prostaglandin E2 (PGE2), a bioactive eicosanoid, has been implicated in many biological processes including reproduction, inflammation and tumor growth. We previously showed that PGE2 stimulated lung cancer cell growth and progression through PGE2 receptor EP2/EP4-mediated kinase signaling pathways. However, the role of PGE2 in controlling lung airway epithelial cell phenotype remains unknown. We evaluated the effects of c-Jun and 3-phosphoinositede dependent protein kinase-1 (PDK1) in mediating epithelial cell hyperplasia induced by PGE2. The bronchial epithelial cell lines BEAS-2B and HBEc14-KT were cultured and then treated with PGE2. PDK1 small interfering RNA (siRNA) and a PDK1 inhibitor, an antagonist of the PGE2 receptor subtype EP4 and EP4 siRNA, c-Jun siRNA, and overexpressions of c-Jun and PDK1 have been used to evaluate the effects on cell proliferation. We demonstrated that PGE2 increased normal bronchial epithelial cell proliferation through induction of PDK1, an ankyrin repeat-containing Ser/Thr kinase implicated in the induction of apoptosis and the suppression of tumor growth. PDK1 siRNA and a PDK1 inhibitor blocked the effects of PGE2 on normal cell growth. The PGE2-induced PDK1 expression was blocked by an antagonist of the PGE2 receptor subtype EP4 and by EP4 siRNA. In addition, we showed that induction of PDK1 by PGE2 was associated with induction of the transcription factor, c-Jun protein. Silencing of c-Jun using siRNA and point mutations of c-Jun sites in the PDK1 gene promoter resulted in blockade of PDK1 expression and promoter activity induced by PGE2. In contrast, overexpression of c-Jun induced PDK1 gene promoter activity and expression followed increased cell proliferation. PGE2 increases normal bronchial epithelial cell proliferation through increased PDK1 gene expression that is dependent on EP4 and induction of c-Jun. Therewith, our data suggest a new role of c-Jun and PDK1 in mediating epithelial cell

Reporting of noninferiority and equivalence randomized trials for major prostaglandins: A systematic survey of the ophthalmology literature

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Rachlis Beth

2008-12-01

Full Text Available Abstract Background Standards for reporting clinical trials have improved the transparency of patient-important research. The Consolidated Standards of Reporting Trials (CONSORT published an extension to address noninferiority and equivalence trials. We aimed to determine the reporting quality of prostaglandin noninferiority and equivalence trials in the treatment of glaucoma. Methods We searched, independently and in duplicate, 6 electronic databases for eligible trials evaluating prostaglandins. We abstracted data on reporting of methodological criteria, including reporting of per-protocol [PP] and intention-to-treat [ITT] analysis, sample size estimation with margins, type of statistical analysis conducted, efficacy summaries, and use of hyperemia measures. Results Trials involving the four major prostaglandin groups (latanoprost, travoprost, bimatoprost, unoprostone were analyzed. We included 36 noninferiority and 11 equivalence trials. Seventeen out of the included 47 trials (36%, 95% Confidence Intervals [CI]: 24–51 were crossover designs. Only 3 studies (6%, 95% CI: 2–17 reported a presented results of both ITT and PP populations. Twelve studies (26%, 95% CI: 15–39 presented only ITT results but mentioned that PP population had similar results. Thirteen trials (28%, 95% CI: 17–42 presented only PP results with no mention of ITT population results while 17 studies (36%, 95% CI: 24–51 presented only ITT results with no mention of PP population results. Thirty-four (72%, 95% CI: 58–83 of studies adequately described their margin of noninferiority/equivalence. Sequence generation was reported in 22/47 trials (47%, 95% CI: 33–61. Allocation concealment was reported in only 10/47 (21%, 95% CI: 12–35 of the trials. Thirty-five studies (74%, 95% CI: 60–85 employed masking of at least two groups, 4/47 (9%, 95% CI: 3–20 masked only patients and 8/47 (17%, 95% CI: 9–30 were open label studies. Eight (17%, 95% CI: 9–30 of the

Delta(9)-tetrahydrocannabinol inhibits 17beta-estradiol-induced proliferation and fails to activate androgen and estrogen receptors in MCF7 human breast cancer cells.

Science.gov (United States)

von Bueren, A O; Schlumpf, M; Lichtensteiger, W

2008-01-01

Delta(9)-tetrahydrocannabinol (THC) exerts palliative effects in cancer patients, but produces adverse effects on the endocrine and reproductive systems. Experimental evidence concerning such effects is controversial. Whether THC exhibits estrogenic or androgenic activity in vitro was investigated. Estrogenic effects of THC were analyzed in vitro by measuring the proliferation of estrogen-sensitive MCF7 cells. Androgenic activity was investigated by the A-Screen assay that measures androgen-dependent inhibition of proliferation of the androgen receptor (AR)-positive human mammary carcinoma cell line, MCF7-AR1. In contrast to 17beta-estradiol, included as positive control with an EC50 value (concentration required for 50% of maximal 17beta-estradiol-induced proliferation) of 1.00 x 10(-12) M, THC failed to induce cell proliferation in the MCF7 cell line at concentrations between 10(-13) and 10(-4) M. THC inhibited 17beta-estradiol-induced proliferation in wild-type MCF7 and MCF7-AR1 cells, with an IC50 value of 2.6 x 10(-5) M and 9 x 10(-6) M, respectively. THC failed to act as an estrogen, but antagonized 17beta-estradiol-induced proliferation. This effect was independent of the AR expression level.

16,16-dimethyl prostaglandin E/sub 2/ increases survival of murine intestinal stem cells when given before photon radiation

Energy Technology Data Exchange (ETDEWEB)

Hanson, W.R.; Thomas, C.

1983-11-01

A variety of prostaglandins (PG) protect the gastric and intestinal mucosa when given before damaging agents as absolute ethanol, acidified taurocholate, boiling water, or nonsteroidal anti-inflammatory agents (NSAI). A synthetic prostaglandin, 16,16-dimethyl PGE/sub 2/, shown to be cytoprotective at physiologic levels to the above agents was given to mice 1 h before or 15 min after /sup 137/Cs gamma(..gamma..) whole-body irradiation. The survival of intestinal stem cells measured by their ability to form in situ colonies of regenerating epithelium was increased stem cells measured by their ability to form in situ colonies of regenerating epithelium was increased when 16,16-dimethyl PGE/sub 2/ was given before but not after /sup 137/Cs ..gamma.. irradiation. The maximum degree of 16,16-dimethyl PGE/sub 2/-induced radioprotection was seen when the drug was given 1 h before irradiation. No radioprotection was seen when the interval between drug and irradiation was 3 h or longer. When the time between 16,16-dimethyl PGE/sub 2/ and irradiation was kept at 1 h, the degree of radioprotection was dependent on the PG drug dose. There was a steep rise in the number of surviving cells at low doses of PG. These results imply that tumors which secrete PGE/sub 2/ may in part be protected from the lethal effects of ionizing photon radiation.

Human urinary excretion profile after smoking and oral administration of ( sup 14 C)delta 1-tetrahydrocannabinol

Energy Technology Data Exchange (ETDEWEB)

Johansson, E.; Gillespie, H.K.; Halldin, M.M. (BMC, Uppsala (Sweden))

1990-05-01

The urinary excretion profiles of delta 1-tetrahydrocannabinol (delta 1-THC) metabolites have been evaluated in two chronic and two naive marijuana users after smoking and oral administration of ({sup 14}C)delta 1-THC. Urine was collected for five days after each administration route and analyzed for total delta 1-THC metabolites by radioactivity determination, for delta 1-THC-7-oic acid by high-performance liquid chromatography, and for cross-reacting cannabinoids by the EMIT d.a.u. cannabinoid assay. The average urinary excretion half-life of {sup 14}C-labeled delta 1-THC metabolites was calculated to be 18.2 +/- 4.9 h (+/- SD). The excretion profiles of delta 1-THC-7-oic acid and EMIT readings were similar to the excretion profile of {sup 14}C-labeled metabolites in the naive users. However, in the chronic users the excretion profiles of delta 1-THC-7-oic acid and EMIT readings did not resemble the radioactive excretion due to the heavy influence from previous Cannabis use. Between 8-14% of the radioactive dose was recovered in the urine in both user groups after oral administration. Lower urinary recovery was obtained both in the chronic and naive users after smoking--5 and 2%, respectively.

The $\\Delta I = 1/2 $ Rule in the Light of Two-Dimensional QCD

CERN Document Server

Ellis, John R.; Hanany, Amihay; Karliner, Marek; Ellis, John; Frishman, Yitzhak; Hanany, Amihay; Karliner, Marek

1997-01-01

We calculate in QCD$_2$ the ratios of baryonic matrix elements of $\\Delta I = 2$ and $\\Delta I = 0$ four-fermion operators, with a view to understanding better the mechanism of $\\Delta I = 1/2$ enhancement in QCD$_4$. We find relatively small suppressions of both the scalar-scalar and vector-vector these results, in view of a suggestion that gluon condensation may be an important contributing factor in the $\\Delta I = 1/2$ enhancement seen in QCD$_4$. At the technical level, our calculation of the vector-vector operator matrix element requires a treatment of the time dependence of the QCD$_2$ soliton which had not been developed in previous phenomenological calculations within this model.

Migration of allosensitized helper but not cytolytic T-lymphocyte clones is inhibited by prostaglandin E2

International Nuclear Information System (INIS)

Jordan, M.L.; Hoffman, R.A.; Simmons, R.L.

1986-01-01

The authors have previously reported that random migration of one clone of C57BL/6 anti DBA/2 helper lymphocytes is significantly inhibited by physiologic concentrations of prostaglandin E 2 (PGE 2 ). The present studies were designed to determine if lymphocyte locomotor responses to PGE 2 are dictated by (1) clone effector function and/or (2) the presence of specific cell surface binding sites for PGE 2 . Random locomotion of eight different lymphocyte clones (all C57BL/6 anti DBA/2) was studied in a modified Boyden chamber assay. Clone function was characterized as helper (H, n = 3), cytolytic (C, n = 4) or cytolytic only in the presence of lectin (L, n = 1). Random migration of all H clones was consistently inhibited by PGE 2 . However, none of the clones possessing a lytic mechanism (C or L) were inhibited by even the highest (1000 ng/ml) concentration of PGE 2 tested. Incubation of clones with 3 H-PGE 2 in the presence of excess unlabelled PGE 2 did not demonstrate specific binding of PGE 2 to either H or C clones. The authors conclude that (1) the effects of PGE 2 on lymphocyte random migration are effector function specific and (2) these responses do not appear to be mediated by specialized cell surface receptors for PGE 2 . Subset specific locomotor responses to PGE 2 may constitute a mechanism whereby lymphocytes with distinct effector functions may differentially accumulate at sites of inflammation

Prostaglandins and complement changes in some conditions related to inflammation. [Mice

Energy Technology Data Exchange (ETDEWEB)

Eisen, V.; Walker, D.I.; Binysh, S.G.; Tedder, R.S.

1977-01-01

Exposure to ionizing radiation produces several systemic and local reactions which could be mediated by prostaglandins. Prostaglandin levels were therefore studied in blood and tissues of mice which had been exposed to x-rays. Significant increases were found in spleens after 200 to 700 R, and in lungs after 600 to 700 R. These changes were most pronounced 4 to 7 days after irradiation. Ionizing radiation promptly and potently reduced the activity of prostaglandin dehydrogenase in the spleen, whereas prostaglandin synthesis was less affected. Evidence was obtained for the activation and consumption of haemolytic complement in serum in the course of heart-lung operations involving extracorporeal circulation. Activation involved primarily the classical pathway, and only slightly the alternate pathway.

Radiation-induced increases in sensitivity of cataleptic behavior to haloperidol: possible involvement of prostaglandins

International Nuclear Information System (INIS)

Joseph, J.A.; Kandasamy, S.B.; Hunt, W.A.; Dalton, T.K.; Stevens, S.

1988-01-01

The effects of radiation exposure on haloperidol-induced catalepsy were examined in order to determine whether elevated prostaglandins, through an action on dopaminergic autoreceptors, could be involved in the radiation-induced increase in the potency of this neuroleptic. Cataleptic behavior was examined in animals irradiated with various doses of gamma photons (1-150 Gy) and pretreated with a subthreshold dose of haloperidol (0.1 mg/kg). This approach was chosen to maximize any synergistic effects of radiation and haloperidol. After irradiation with doses less than or equal to 30 Gy, the combined treatment of haloperidol and radiation produced catalepsy, whereas neither treatment alone had an effect. This observed catalepsy could be blocked with prior administration of indomethacin, a prostaglandin synthesis inhibitor. Animals exposed to doses of radiation less than or equal to 50 Gy and no haloperidol, however, displayed apparent catalepsy. This effect was also antagonized by indomethacin. Prostaglandins can induce catalepsy and when administered in subthreshold doses along with subthreshold doses of haloperidol, catalepsy was observed. In order to assess a possible action of prostaglandins and radiation on dopaminergic activity, the functioning of striatal dopaminergic autoreceptors was examined by determining the effects of varying concentrations of haloperidol on the K+-evoked release of dopamine from striatal slices obtained from parallel groups of animals treated as above. Results indicated that sensitivity to haloperidol increased (higher K+-evoked dopamine release) in slices from irradiated or prostaglandin-treated animals and that this increase in sensitivity was blocked by indomethacin

Matrix metalloproteinase activity and prostaglandin E2 are elevated in the synovial fluid of meniscus tear patients.

Science.gov (United States)

Liu, Betty; Goode, Adam P; Carter, Teralyn E; Utturkar, Gangadhar M; Huebner, Janet L; Taylor, Dean C; Moorman, Claude T; Garrett, William E; Kraus, Virginia B; Guilak, Farshid; DeFrate, Louis E; McNulty, Amy L

Meniscus tears are a common knee injury and are associated with the development of post-traumatic osteoarthritis (OA). The purpose of this study is to evaluate potential OA mediators in the synovial fluid and serum of meniscus tear subjects compared to those in the synovial fluid of radiographic non-OA control knees. Sixteen subjects with an isolated unilateral meniscus injury and six subjects who served as reference controls (knee Kellgren-Lawrence grade 0-1) were recruited. Twenty-one biomarkers were measured in serum from meniscus tear subjects and in synovial fluid from both groups. Meniscus tear subjects were further stratified by tear type to assess differences in biomarker levels. Synovial fluid total matrix metalloproteinase (MMP) activity and prostaglandin E2 (PGE2) were increased 25-fold and 290-fold, respectively, in meniscus tear subjects as compared to reference controls (p meniscus tear subjects (R = 0.83, p meniscus tear subjects, synovial fluid levels of MMP activity, MMP-2, MMP-3, sGAG, COMP, IL-6, and PGE2 were higher than serum levels (p meniscus tears had higher synovial fluid MMP-10 (p meniscus injury may be targets to promote meniscus repair and prevent OA development.

Export of cyclic AMP by avian red cells and inhibition by prostaglandin A1

International Nuclear Information System (INIS)

Heasley, L.E.

1985-01-01

The mechanism by which PGA 1 inhibits cAMP export by avian red cells was studied, to provide details on the molecular mechanism of a prostaglandin action and on the process of cAMP export itself. The interaction of PGA 1 with pigeon red cells is a multi-step process of uptake, metabolism and secretion. [ 3 H]PGA rapidly enters red cells and is promptly metabolized (V/sub max/ ≥ 1 nmol/min/10 7 cells) to a compound (5) that remains in the aqueous layer after ethyl acetate extraction. Chromatographic analyses, amino acid content and fast atom bombardment mass spectrometry reveal that the polar metabolite is conjugated with glutathione (PGA 1 -GSH) at C-11 via a thioether bond and is largely (80%) reduced to the C-9 hydroxyl derivative

Prostaglandin E2 activates the mTORC1 pathway through an EP4/cAMP/PKA- and EP1/Ca2+-mediated mechanism in the human pancreatic carcinoma cell line PANC-1.

Science.gov (United States)

Chang, Hui-Hua; Young, Steven H; Sinnett-Smith, James; Chou, Caroline Ei Ne; Moro, Aune; Hertzer, Kathleen M; Hines, Oscar Joe; Rozengurt, Enrique; Eibl, Guido

2015-11-15

Obesity, a known risk factor for pancreatic cancer, is associated with inflammation and insulin resistance. Proinflammatory prostaglandin E2 (PGE2) and elevated insulin-like growth factor type 1 (IGF-1), related to insulin resistance, are shown to play critical roles in pancreatic cancer progression. We aimed to explore a potential cross talk between PGE2 signaling and the IGF-1/Akt/mammalian target of rapamycin complex 1 (mTORC1) pathway in pancreatic cancer, which may be a key to unraveling the obesity-cancer link. In PANC-1 human pancreatic cancer cells, we showed that PGE2 stimulated mTORC1 activity independently of Akt, as evaluated by downstream signaling events. Subsequently, using pharmacological and genetic approaches, we demonstrated that PGE2-induced mTORC1 activation is mediated by the EP4/cAMP/PKA pathway, as well as an EP1/Ca(2+)-dependent pathway. The cooperative roles of the two pathways were supported by the maximal inhibition achieved with the combined pharmacological blockade, and the coexistence of highly expressed EP1 (mediating the Ca(2+) response) and EP2 or EP4 (mediating the cAMP/PKA pathway) in PANC-1 cells and in the prostate cancer line PC-3, which also robustly exhibited PGE2-induced mTORC1 activation, as identified from a screen in various cancer cell lines. Importantly, we showed a reinforcing interaction between PGE2 and IGF-1 on mTORC1 signaling, with an increase in IL-23 production as a cellular outcome. Our data reveal a previously unrecognized mechanism of PGE2-stimulated mTORC1 activation mediated by EP4/cAMP/PKA and EP1/Ca(2+) signaling, which may be of great importance in elucidating the promoting effects of obesity in pancreatic cancer. Ultimately, a precise understanding of these molecular links may provide novel targets for efficacious interventions devoid of adverse effects. Copyright © 2015 the American Physiological Society.

Female Sex Hormones Influence the Febrile Response Induced by Lipopolysaccharide, Cytokines and Prostaglandins but not by Interleukin-1β in Rats.

Science.gov (United States)

Brito, H O; Radulski, D R; Wilhelms, D B; Stojakovic, A; Brito, L M O; Engblom, D; Franco, C R C; Zampronio, A R

2016-10-01

There are differences in the immune response, and particularly fever, between males and females. In the present study, we investigated how the febrile responses induced by lipopolysaccharide (LPS) and different endogenous pyrogens were affected by female gonadal hormones. The febrile response to i.p. injection of LPS (50 μg/kg) was 40% lower in female rats compared to male or ovariectomised (OVX) female rats. Accordingly, oestrogen replacement in OVX animals reduced LPS-induced fever. Treatment with the prostaglandin synthesis inhibitor indomethacin (2 mg/kg, i.p. 30 min before) reduced the febrile response induced by LPS in both OVX (88%) and sham-operated (71%) rats. In line with the enhanced fever in OVX rats, there was increased expression of cyclooxygenase-2 (COX-2) in the hypothalamus and elevated levels of prostaglandin E 2 (PGE 2 ). In addition, OVX rats were hyper-responsive to PGE 2 injected i.c.v. By contrast to the enhanced fever in response to LPS and PGE 2 , the febrile response induced by i.c.v. injection of interleukin (IL)-1β was unaffected by ovariectomy, whereas the responses induced by tumour necrosis factor (TNF)-α and macrophage inflammatory protein (MIP)-1α were completely abrogated. These results suggest that the mediators involved in the febrile response in females are similar to males, although the reduction of female hormones may decrease the responsiveness of some mediators such as TNF-α and MIP-1α. Compensatory mechanisms may be activated in females after ovariectomy such as an augmented synthesis of COX-2 and PGE 2 . © 2016 British Society for Neuroendocrinology.

Aerosolized PGE1, PGI2 and nitroprusside protect against vascular leakage in lung ischaemia-reperfusion.

Science.gov (United States)

Schütte, H; Löckinger, A; Seeger, W; Grimminger, F

2001-07-01

High permeability oedema is an important feature in lung injury secondary to ischaemia-reperfusion. This study investigated the influence of aerosolized prostaglandin E1 (PGE1), prostaglandin I2 (PCI2) and the nitric oxide (NO)-donor, sodium nitroprusside (SNP) on microvascular barrier function in pulmonary ischaemia-reperfusion. Buffer-perfused rabbit lungs were exposed to 180 or 210 min of warm ischaemia while maintaining anoxic ventilation and a positive intravascular pressure. Reperfusion provoked a transient, mostly precapillary elevation of vascular resistance, followed by a severe increase of the capillary filtration coefficient (Kfc) versus nonischaemic controls (3.17+/-0.34 versus 0.85+/-0.05 cm3 x s(-1) cmH2O(-1) x g(-1) x 10(-4) after 30 min of reperfusion), and progressive oedema formation. Short-term aerosolization of SNP, PGE1 or PGI2 at the beginning of ischaemia largely suppressed the Kfc increase (1.36+/-0.22, 1.32+/-0.23 and 1.32+/-0.22 cm3 x s(-1) x cmH2O(-1) x g(-1) x 10(-4), respectively) and oedema formation. In contrast, application prior to reperfusion was much less effective, with some reduction of Kfc increase by PGI2 and SNP and no effect of PGE, (1.79+/-0.31, 2.2+/-0.53 and 3.2+/-0.05 cm3 x s(-1) x cmH2O(-1) x g(-1) x 10(-4), respectively). Haemodynamics, including microvascular pressure, were only marginally affected by the chosen doses of aerosolized vasodilators. It is concluded that short-term aerosolization of prostaglandin E1, prostaglandin I2 and sodium nitroprusside at the onset of ischaemia is highly effective in maintaining endothelial barrier properties in pulmonary ischaemia-reperfusion. This effect is apparently attributable to nonvasodilatory mechanisms exerted by these agents. Alveolar deposition of prostaglandins and/or nitric oxide donors by the aerosol technique may offer pulmonary protection in ischaemia-reperfusion injury.

Isótopos estáveis e produção de bebidas: de onde vem o carbono que consumimos?

Directory of Open Access Journals (Sweden)

Oliveira Ana Cristina B.

2002-01-01

Full Text Available A composição isotópica do carbono (delta13C foi utilizada na determinação da origem botânica (C3 x C4 de amostras de café, vinho, cerveja e vodka, de diferentes marcas e procedências, comercializadas no Brasil. Dentre as marcas de café analisadas, apenas uma apresentou um elevado percentual de plantas C4 em sua composição, evidenciado pelo valor de delta13C (-16,2‰. Os valores de delta13C das amostras de vinhos brasileiros, variaram entre -25,1 e -17,1‰, indicando a presença de carbono de origem C4 nas amostras que tiveram os maiores valores de delta13C. Duas marcas de vinhos importados, por sua vez, apresentaram delta13C característico de planta C3 (-27,1 e -26,3‰. Os valores de delta13C das vodkas importadas variaram entre -26,4 e -23,9‰, e as brasileiras entre -12,8 e -11,8‰, excetuando-se uma marca que apresentou valor -23,1‰. As marcas de cervejas importadas, em sua maioria, apresentaram valores mais negativos (-27,3 a -20,7‰ que as nacionais (-25,9 a -18,4‰. Estes resultados evidenciam a eficiência desta metodologia na determinação da origem do C e percentual de mistura destas bebidas.

n3 and n6 polyunsaturated fatty acids differentially modulate prostaglandin E secretion but not markers of lipogenesis in adipocytes

Directory of Open Access Journals (Sweden)

Saxton Arnold M

2009-01-01

Full Text Available Abstract A dramatic rise in the incidence of obesity in the U.S. has accelerated the search for interventions that may impact this epidemic. One recently recognized target for such intervention is adipose tissue, which secretes a variety of bioactive substances including prostaglandins. Prostaglandin E2 (PGE2 has been shown to decrease lipolysis in adipocytes, but limited studies have explored alternative mechanisms by which PGE2 might impact obesity, such as adipogenesis or lipogenesis. Studies conducted on ApcMin/+ mice indicated that selective inhibition of the cyclooxygenase (COX-2 enzyme led to significant reductions in fatty acid synthase (FAS activity in adipose tissue suggesting lipogenic effects of PGE2. To further investigate whether these lipid mediators directly regulate lipogenesis, we used 3T3-L1 adipocytes to determine the impact of eicosapentaenoic acid (EPA and celecoxib on PGE2 formation and FAS used as a lipogenic marker. Both arachidonic acid (AA and EPA dose-dependently increased PGE secretion from adipocytes. AA was expectedly more potent and exhibiting at 150 uM dose a 5-fold increase in PGE2 secretion over EPA. Despite higher secretion of PGE by EPA and AA compared to control, neither PUFA significantly altered FAS activity. By contrast both AA and EPA significantly decreased FAS mRNA levels. Addition of celecoxib, a selective COX-2 inhibitor, significantly decreased PGE2 secretion (p 2 and celecoxib further decreased the FAS activity compared to PGE2 alone or untreated controls. In conclusion, EPA-mediated inhibition of AA metabolism did not significantly alter FAS activity while both AA and EPA significantly decreased FAS mRNA expression. COX-2 inhibition significantly decreased PGE2 production resulting in a decrease in FAS activity and expression that was not reversed with the addition of exogenous PGE2, suggesting an additional mechanism that is independent of COX-2.

Prostaglandins, masculinization and its disorders: effects of fetal exposure of the rat to the cyclooxygenase inhibitor- indomethacin.

Directory of Open Access Journals (Sweden)

Afshan Dean

Full Text Available Recent studies have established that masculinization of the male reproductive tract is programmed by androgens in a critical fetal 'masculinization programming window' (MPW. What is peculiar to androgen action during this period is, however, unknown. Studies from 20 years ago in mice implicated prostaglandin (PG-mediation of androgen-induced masculinization, but this has never been followed up. We therefore investigated if PGs might mediate androgen effects in the MPW by exposing pregnant rats to indomethacin (which blocks PG production by inhibiting cyclooxygenase activity during this period and then examining if androgen production or action (masculinization was affected. Pregnant rats were treated with indomethacin (0.8 mg/kg/day; e15.5-e18.5 to encompass the MPW. Indomethacin exposure decreased fetal bodyweight (e21.5, testis weight (e21.5 and testicular PGE2 (e17.5, e21.5, but had no effect on intratesticular testosterone (ITT; e17.5 or anogenital index (AGI; e21.5. Postnatally, AGI, testis weight and blood testosterone were unaffected by indomethacin exposure and no cryptorchidism or hypospadias occurred. Penis length was normal in indomethacin-exposed animals at Pnd25 but was reduced by 26% (p<0.001 in adulthood, an effect that is unexplained. Our results demonstrate that indomethacin can effectively decrease intra-testicular PGE2 level. However, the resulting male phenotype does not support a role for PGs in mediating androgen-induced masculinization during the MPW in rats. The contrast with previous mouse studies is unexplained but may reflect a species difference.

BTB-BACK Domain Protein POB1 Suppresses Immune Cell Death by Targeting Ubiquitin E3 ligase PUB17 for Degradation.

Directory of Open Access Journals (Sweden)

Beatriz Orosa

2017-01-01

Full Text Available Hypersensitive response programmed cell death (HR-PCD is a critical feature in plant immunity required for pathogen restriction and prevention of disease development. The precise control of this process is paramount to cell survival and an effective immune response. The discovery of new components that function to suppress HR-PCD will be instrumental in understanding the regulation of this fundamental mechanism. Here we report the identification and characterisation of a BTB domain E3 ligase protein, POB1, that functions to suppress HR-PCD triggered by evolutionarily diverse pathogens. Nicotiana benthamiana and tobacco plants with reduced POB1 activity show accelerated HR-PCD whilst those with increased POB1 levels show attenuated HR-PCD. We demonstrate that POB1 dimerization and nuclear localization are vital for its function in HR-PCD suppression. Using protein-protein interaction assays, we identify the Plant U-Box E3 ligase PUB17, a well established positive regulator of plant innate immunity, as a target for POB1-mediated proteasomal degradation. Using confocal imaging and in planta immunoprecipitation assays we show that POB1 interacts with PUB17 in the nucleus and stimulates its degradation. Mutated versions of POB1 that show reduced interaction with PUB17 fail to suppress HR-PCD, indicating that POB1-mediated degradation of PUB17 U-box E3 ligase is an important step for negative regulation of specific immune pathways in plants. Our data reveals a new mechanism for BTB domain proteins in suppressing HR-PCD in plant innate immune responses.

Studying medium effects with the optimized {delta} expansion

Energy Technology Data Exchange (ETDEWEB)

Krein, G [Instituto de Fisica Teorica (IFT), Sao Paulo, SP (Brazil); Menezes, D P [Santa Catarina Univ., Florianopolis, SC (Brazil). Dept. de Fisica; Nielsen, M [Sao Paulo Univ., SP (Brazil). Inst. de Fisica; Pinto, M B [Montpellier-2 Univ., 34 (France). Lab. de Physique Mathematique

1995-04-01

The possibility of using the optimized {delta} expansion for studying medium effects on hadronic properties in quark or nuclear matter is investigated. The {delta} expansion is employed to study density effects with two commonly used models in hadron and nuclear physics, the Nambu-Jona-Lasinio model for the dynamical chiral symmetry breaking and the Walecka model for the equation of state of nuclear matter. The results obtained with the {delta} expansion are compared to those obtained with the traditional Hartree-Fock approximation. Perspectives for using the {delta} expansion in other field theoretic models in hadron and nuclear physics are discussed. (author). 17 refs, 9 figs.

Smilansky-Solomyak model with a delta '-interaction

Czech Academy of Sciences Publication Activity Database

Exner, Pavel; Lipovský, J.

2018-01-01

Roč. 382, č. 18 (2018), s. 1207-1213 ISSN 0375-9601 R&D Projects: GA ČR GA17-01706S Institutional support: RVO:61389005 Keywords : Smilansky-Solomyak model * delta '-interaction * spectral theory Subject RIV: BE - Theoretical Physics OBOR OECD: Atomic, molecular and chemical physics ( physics of atoms and molecules including collision, interaction with radiation, magnetic resonances, Mössbauer effect) Impact factor: 1.772, year: 2016

Identification of di- and tri-substituted hydroxy and ketone metabolites of delta1-tetrahydrocannabinol in mouse liver.

Science.gov (United States)

Harvey, D J; Martin, B R; Paton, W D

1977-08-01

In vivo liver metabolites of delta1-tetrahydrocannabinol (delta1-THC) were examined with a gas chromatograph--mass spectrometer--computer system as trimethylsilyl (TMS), [2H9]TMS and methyloxime-TMS derivatives. In addition to the reported monohydroxy, acid, and hydroxyacid metabolites, the following multiply substituted metabolites were identified: 2'',7-, 3'', 7-, and 6beta,7-dihydroxy-delta1-THC; 2'',6alpha,7-, and 3'',6alpha,7-trihydroxy-delta1-THC; 2''-, 3''-, and 7-hydroxy-6-oxo-delta1-THC, and 2'',7- and 3'',7-dihydroxy-6-oxo-delta1-THC. The ketones and hydroxyacids were reduced to common alcohols with lithium aluminium deuteride and the number of deuterium atoms in the product was used to distinguish the metabolic alcohols from those produced by reduction.

A novel mouse PKC{delta} splice variant, PKC{delta}IX, inhibits etoposide-induced apoptosis

Energy Technology Data Exchange (ETDEWEB)

Kim, Jung D. [School of Biological Sciences, University of Ulsan, Ulsan (Korea, Republic of); Seo, Kwang W. [Department of Internal Medicines, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan (Korea, Republic of); Lee, Eun A.; Quang, Nguyen N. [School of Biological Sciences, University of Ulsan, Ulsan (Korea, Republic of); Cho, Hong R. [Department of Surgery, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan (Korea, Republic of); Biomedical Research Center, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan (Korea, Republic of); Kwon, Byungsuk, E-mail: bskwon@mail.ulsan.as.kr [School of Biological Sciences, University of Ulsan, Ulsan (Korea, Republic of); Biomedical Research Center, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan (Korea, Republic of)

2011-07-01

Highlights: {yields} A novel PKC{delta} isoform, named PKC{delta}IX, that lacks the C1 domain and the ATP-binding site is ubiquitously expressed. {yields} PKC{delta}IX inhibits etoposide-induced apoptosis. {yields} PKC{delta}IX may function as an endogenous dominant negative isoform for PKC{delta}. -- Abstract: Protein kinase C (PKC) {delta} plays an important role in cellular proliferation and apoptosis. The catalytic fragment of PKC{delta} generated by caspase-dependent cleavage is essential for the initiation of etoposide-induced apoptosis. In this study, we identified a novel mouse PKC{delta} isoform named PKC{delta}IX (Genebank Accession No. (HQ840432)). PKC{delta}IX is generated by alternative splicing and is ubiquitously expressed, as seen in its full-length PKC{delta}. PKC{delta}IX lacks the C1 domain, the caspase 3 cleavage site, and the ATP binding site but preserves an almost intact c-terminal catalytic domain and a nuclear localization signal (NLS). The structural characteristics of PKC{delta}IX provided a possibility that this PKC{delta} isozyme functions as a novel dominant-negative form for PKC{delta} due to its lack of the ATP-binding domain that is required for the kinase activity of PKC{delta}. Indeed, overexpression of PKC{delta}IX significantly inhibited etoposide-induced apoptosis in NIH3T3 cells. In addition, an in vitro kinase assay showed that recombinant PKC{delta}IX protein could competitively inhibit the kinase activity of PKC{delta}. We conclude that PKC{delta}IX can function as a natural dominant-negative inhibitor of PKC{delta}in vivo.

Prostaglandin H synthase immunoreactivity in human gut. An immunohistochemical study

DEFF Research Database (Denmark)

Mikkelsen, H B; Rumessen, J J; Qvortrup, Klaus

1991-01-01

Prostaglandins exhibit a variety of actions on intestinal smooth muscle depending upon the type, dose and muscle layer studied. As the cellular origin of prostaglandin H (PGH) synthase has not been established with certainty in the human gut wall, we studied the localization of PGH synthase...

Alpha 1-adrenergic receptor-mediated phosphoinositide hydrolysis and prostaglandin E2 formation in Madin-Darby canine kidney cells. Possible parallel activation of phospholipase C and phospholipase A2

International Nuclear Information System (INIS)

Slivka, S.R.; Insel, P.A.

1987-01-01

alpha 1-Adrenergic receptors mediate two effects on phospholipid metabolism in Madin-Darby canine kidney (MDCK-D1) cells: hydrolysis of phosphoinositides and arachidonic acid release with generation of prostaglandin E2 (PGE2). The similarity in concentration dependence for the agonist (-)-epinephrine in eliciting these two responses implies that they are mediated by a single population of alpha 1-adrenergic receptors. However, we find that the kinetics of the two responses are quite different, PGE2 production occurring more rapidly and transiently than the hydrolysis of phosphoinositides. The antibiotic neomycin selectively decreases alpha 1-receptor-mediated phosphatidylinositol 4,5-bisphosphate hydrolysis without decreasing alpha 1-receptor-mediated arachidonic acid release and PGE2 generation. In addition, receptor-mediated inositol trisphosphate formation is independent of extracellular calcium, whereas release of labeled arachidonic acid is largely calcium-dependent. Moreover, based on studies obtained with labeled arachidonic acid, receptor-mediated generation of arachidonic acid cannot be accounted for by breakdown of phosphatidylinositol monophosphate, phosphatidylinositol bisphosphate, or phosphatidic acid. Further studies indicate that epinephrine produces changes in formation or turnover of several classes of membrane phospholipids in MDCK cells. We conclude that alpha 1-adrenergic receptors in MDCK cells appear to regulate phospholipid metabolism by the parallel activation of phospholipase C and phospholipase A2. This parallel activation of phospholipases contrasts with models described in other systems which imply sequential activation of phospholipase C and diacylglycerol lipase or phospholipase A2

[mRNA expression of notch ligand-delta-like-1 and jagged-1 in mesenchymal stem cells of MDS patients].

Science.gov (United States)

Fei, Cheng-Ming; Gu, Shu-Cheng; Zhao, You-Shan; Guo, Juan; Li, Xiao; Chang, Chun-Kang

2014-12-01

This study was aimed to investigated the mRNA expression levels of Notch ligands- Delta-like-1 and Jagged-1 in bone marrow mesenchymal stem cells of patients with myelodysplastic syndrome (MDS), and to explore their relation with onset of MDS. Bone marrow mesenchymal stem cells of 38 patients with MDS and 16 normal subjects as control were collected to detect mRNA expression of Delta-like-1 and Jagged-1 by using real-time quantitative polymerase chain reaction. The results showed that the expression levels of Delta-like-1 and Jagged-1 in mesenchymal stem cells of MDS patients were significantly higher than that in normal controls (P MDS patients (r = 0.502, P MDS patients with abnormal karyotypes were significantly higher than those in MDS patients with normal karyotypes (P 0.05). It is concluded that the changes of Delta-like-1 and Jagged-1 expression level in MSC may play a role in the pathogenesis of myelodysplastic syndrome.

Prostaglandin transporter (OATP2A1/SLCO2A1) contributes to local disposition of eicosapentaenoic acid-derived PGE3.

Science.gov (United States)

Gose, Tomoka; Nakanishi, Takeo; Kamo, Shunsuke; Shimada, Hiroaki; Otake, Katsumasa; Tamai, Ikumi

2016-01-01

Eicosapentaenoic acid (EPA)-derived prostaglandin E3 (PGE3) possesses an anti-inflammatory effect; however, information for transporters that regulate its peri-cellular concentration is limited. The present study, therefore, aimed to clarify transporters involved in local disposition of PGE3. PGE3 uptake was assessed in HEK293 cells transfected with OATP2A1/SLCO2A1, OATP1B1/SLCO1B1, OATP2B1/SLCO2B1, OAT1/SLC22A6, OCT1/SLC22A1 or OCT2/SLC22A2 genes, compared with HEK293 cells transfected with plasmid vector alone (Mock). PGE3 uptake by OATP2A1-expressing HEK293 cells (HEK/2A1) was the highest and followed by HEK/1B1, while no significantly higher uptake of PGE3 than Mock cells was detected by other transporters. Saturation kinetics in PGE3 uptake by HEK/2A1 estimated the Km as 7.202 ± 0.595 μM, which was 22 times higher than that of PGE2 (Km=0.331 ± 0.131 μM). Furthermore, tissue disposition of PGE3 was examined in wild-type (WT) and Slco2a1-deficient (Slco2a1(-/-)) mice after oral administration of EPA ethyl ester (EPA-E) when they underwent intraperitoneal injection of endotoxin (e.g., lipopolysaccharide). PGE3 concentration was significantly higher in the lung, and tended to increase in the colon, stomach, and kidney of Slco2a1(-/-), compared to WT mice. Ratio of PGE2 metabolite 15-keto PGE2 over PGE2 concentration was significantly lower in the lung and colon of Slco2a1(-/-) than that of WT mice, suggesting that PGE3 metabolism is downregulated in Slco2a1(-/-) mice. In conclusion, PGE3 was found to be a substrate of OATP2A1, and local disposition of PGE3 could be regulated by OATP2A1 at least in the lung. Copyright © 2015 Elsevier Inc. All rights reserved.

Melanoma cultures show different susceptibility towards E1A-, E1B-19 kDa- and fiber-modified replication-competent adenoviruses.

Science.gov (United States)

Schmitz, M; Graf, C; Gut, T; Sirena, D; Peter, I; Dummer, R; Greber, U F; Hemmi, S

2006-06-01

Replicating adenovirus (Ad) vectors with tumour tissue specificity hold great promise for treatment of cancer. We have recently constructed a conditionally replicating Ad5 AdDeltaEP-TETP inducing tumour regression in a xenograft mouse model. For further improvement of this vector, we introduced four genetic modifications and analysed the viral cytotoxicity in a large panel of melanoma cell lines and patient-derived melanoma cells. (1) The antiapoptotic gene E1B-19 kDa (Delta19 mutant) was deleted increasing the cytolytic activity in 18 of 21 melanoma cells. (2) Introduction of the E1A 122-129 deletion (Delta24 mutant), suggested to attenuate viral replication in cell cycle-arrested cells, did not abrogate this activity and increased the cytolytic activity in two of 21 melanoma cells. (3) We inserted an RGD sequence into the fiber to extend viral tropism to alphav integrin-expressing cells, and (4) swapped the fiber with the Ad35 fiber (F35) enhancing the tropism to malignant melanoma cells expressing CD46. The RGD-fiber modification strongly increased cytolysis in all of the 11 CAR-low melanoma cells. The F35 fiber-chimeric vector boosted the cytotoxicity in nine of 11 cells. Our results show that rational engineering additively enhances the cytolytic potential of Ad vectors, a prerequisite for the development of patient-customized viral therapies.

Prostaglandin A1 metabolism and inhibition of cyclic AMP extrusion by avian erythrocytes

International Nuclear Information System (INIS)

Heasley, L.E.; Brunton, L.L.

1985-01-01

Prostaglandins (PG) inhibit active cyclic AMP export from pigeon red cells, PGA1 and PGA2 most potently. To probe the mechanism of this action of PGA1, the authors have studied the interaction of [ 3 H]PGA1 with suspensions of pigeon red cells. The interaction of PGA1 with pigeon red cells is a multistep process of uptake, metabolism, and secretion. [ 3 H] PGA1 rapidly enters red cells and is promptly metabolized to a compound(s) that remains in the aqueous layer after ethylacetate extraction. The glutathione-depleting agent, diamide, inhibits formation of the PGA1 metabolite. The red cells secrete the polar metabolite of PGA1 by a saturable mechanism that lowered temperatures inhibit. Because uptake and metabolism progress with much greater rates than metabolite secretion, red cells transiently concentrate the polar compound intracellularly. Onset and reversal of inhibition of cyclic AMP export by PGA1 coincide with accumulation and secretion of PGA1 metabolite, suggesting that the polar metabolite acts at an intracellular site to inhibit cyclic AMP efflux

Deformation characteristics of {delta} phase in the delta-processed Inconel 718 alloy

Energy Technology Data Exchange (ETDEWEB)

Zhang, H.Y., E-mail: haiyanzhang@imr.ac.cn [Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); Zhang, S.H., E-mail: shzhang@imr.ac.cn [Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); Cheng, M. [Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); Li, Z.X. [Beijing Institute of Aeronautica1 Materials, Beijing 100095 (China)

2010-01-15

The hot working characteristics of {delta} phase in the delta-processed Inconel 718 alloy during isothermal compression deformation at temperature of 950 deg. C and strain rate of 0.005 s{sup -1}, were studied by using optical microscope, scanning electron microscope and quantitative X-ray diffraction technique. The results showed that the dissolution of plate-like {delta} phase and the precipitation of spherical {delta} phase particles coexisted during the deformation, and the content of {delta} phase decreased from 7.05 wt.% to 5.14 wt.%. As a result of deformation breakage and dissolution breakage, the plate-like {delta} phase was spheroidized and transferred to spherical {delta} phase particles. In the center with largest strain, the plate-like {delta} phase disappeared and spherical {delta} phase appeared in the interior of grains and grain boundaries.

Curcumin reduces prostaglandin E2, matrix metalloproteinase-3 and proteoglycan release in the secretome of interleukin 1β-treated articular cartilage [v1; ref status: indexed, http://f1000r.es/1cl

Directory of Open Access Journals (Sweden)

Abigail L Clutterbuck

2013-07-01

Full Text Available Objective: Curcumin (diferuloylmethane is a phytochemical with potent anti-inflammatory and anti-oxidant properties, and has therapeutic potential for the treatment of a range of inflammatory diseases, including osteoarthritis (OA. The aim of this study was to determine whether non-toxic concentrations of curcumin can reduce interleukin-1beta (IL-1β-stimulated inflammation and catabolism in an explant model of cartilage inflammation. Methods: Articular cartilage explants and primary chondrocytes were obtained from equine metacarpophalangeal joints. Curcumin was added to monolayer cultured primary chondrocytes and cartilage explants in concentrations ranging from 3μM-100μM. Prostaglandin E2 (PGE2 and matrix metalloproteinase (MMP-3 release into the secretome of IL-1β-stimulated explants was measured using a competitive ELISA and western blotting respectively. Proteoglycan (PG release in the secretome was measured using the 1,9-dimethylmethylene blue (DMMB assay. Cytotoxicity was assessed with a live/dead assay in monolayer cultures after 24 hours, 48 hours and five days, and in explants after five days. Results: Curcumin induced chondrocyte death in primary cultures (50μM p<0.001 and 100μM p<0.001 after 24 hours. After 48 hours and five days, curcumin (≥25μM significantly increased cell death (p<0.001 both time points. In explants, curcumin toxicity was not observed at concentrations up to and including 25μM after five days. Curcumin (≥3μM significantly reduced IL-1β-stimulated PG (p<0.05 and PGE2 release (p<0.001 from explants, whilst curcumin (≥12μM significantly reduced MMP-3 release (p<0.01. Conclusion: Non-cytotoxic concentrations of curcumin exert anti-catabolic and anti-inflammatory effects in cartilage explants.

Prostaglandins and Rheumatoid Arthritis

Directory of Open Access Journals (Sweden)

Mohammad Javad Fattahi

2012-01-01

Full Text Available Rheumatoid arthritis (RA is a chronic, autoimmune, and complex inflammatory disease leading to bone and cartilage destruction, whose cause remains obscure. Accumulation of genetic susceptibility, environmental factors, and dysregulated immune responses are necessary for mounting this self-reacting disease. Inflamed joints are infiltrated by a heterogeneous population of cellular and soluble mediators of the immune system, such as T cells, B cells, macrophages, cytokines, and prostaglandins (PGs. Prostaglandins are lipid inflammatory mediators derived from the arachidonic acid by multienzymatic reactions. They both sustain homeostatic mechanisms and mediate pathogenic processes, including the inflammatory reaction. They play both beneficial and harmful roles during inflammation, according to their site of action and the etiology of the inflammatory response. With respect to the role of PGs in inflammation, they can be effective mediators in the pathophysiology of RA. Thus the use of agonists or antagonists of PG receptors may be considered as a new therapeutic protocol in RA. In this paper, we try to elucidate the role of PGs in the immunopathology of RA.

Effect of radioprotectant WR 2721 on cyclic nucleotides, prostaglandins, and lysosomes

International Nuclear Information System (INIS)

Trocha, P.J.; Catravas, G.N.

1983-01-01

Within 1 hr after ip injection of the radioprotectant WR 2721 into rats, splenic cGMP levels dropped and remained suppressed for 6 hr before returning to normal. However, if rats were exposed to ionizing radiation 30-40 min after WR 2721 treatment, they had higher cGMP levels at 3 hr postirradiation than the nonirradiUted, drug-treated controls, but the cGMP content was still found to be lower than that of the irradiated nondrug-treated controls. Radiation exposure of animals pretreated with WR 2721 also resulted in higher liver and spleen levels of cAMP and additional elevations in spleen prostaglandin content, compared with irradiated controls at 3-6 hr after radiation treatment. The secondary fluctuations of lysosomal enzyme activities, prostaglandin content, and cyclic nucleotide levels were also altered in irradiated rats pretreated with WR 2721 when compared with irradiated controls. Liver and spleen lysosomal β-glucuronidase activities, spleen cAMP and cGMP levels, and spleen prostaglandin concentrations were closer to physiological levels at 3 days postirradiation in rats given WR 2721 before the radiation treatment

A role for prostaglandins in rapid cycling suggested by episode-specific gene expression shifts in peripheral blood mononuclear cells

DEFF Research Database (Denmark)

Gurvich, Artem; Begemann, Martin; Dahm, Liane

2014-01-01

and quantitative real-time reverse transcriptase polymerase chain reaction for prostaglandin D2 synthase (PTGDS), aldo-ketoreductase family 1, member C3 (AKR1C3), cyclooxygenase-2 (PAN means all splice variants) (COX2PAN ), prostaglandin-endoperoxide synthase 2 (PTGS2), and purinergic receptor P2X, ligand...

Efficiency, safety, and patient preference of switching from dorzolamide 1%/timolol 0.5% to brinzolamide 1%/timolol 0.5% while maintaining the prostaglandin F2α analog

OpenAIRE

Shimizu, Yoshie; Nakakura,Shunsuke; Nishiyama,Makiko; Tabuchi,Hitoshi; Kiuchi,Yoshiaki

2015-01-01

Yoshie Shimizu,1 Shunsuke Nakakura,1 Makiko Nishiyama,1 Hitoshi Tabuchi,1 Yoshiaki Kiuchi2 1Department of Ophthalmology, Saneikai Tsukazaki Hospital, Himeji, 2Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan Background: We investigated the efficiency, safety and patient preference of switching from dorzolamide 1%/timolol 0.5% to brinzolamide 1%/timolol 0.5% while maintaining the prostaglandin F2α analog...

Does prostaglandin-E1 modulate d-galactosamine induced cell ...

African Journals Online (AJOL)

Sameh S. Tawfik

2015-01-05

Jan 5, 2015 ... removed during hepatectomy operation to liver cancer patients, and isolated using the classical col- .... and solitary lesion at segment IV b and the other two cases ... 0.2 g/l glutamine, 50 mg/l vitamin C, 0.04 mg/l dexa-metha-.

Prostaglandin synthesis can be inhibited locally by infusion of NSAIDS through microdialysis catheters in human skeletal muscle

DEFF Research Database (Denmark)

Mikkelsen, Ulla Ramer; Helmark, Ida Carøe; Kjaer, Michael

2008-01-01

of nonsteroidal anti-inflammatory drugs (NSAIDs). However, to study the local role of prostaglandins, the formation of prostaglandins within the tissue must be controlled. Microdialysis enables determination of local concentrations of water-soluble substances within the tissue. In the present study......, the microdialysis method was used to infuse NSAIDs locally into human skeletal muscles producing a local block of prostaglandin formation. In addition, the graded blockade at various distances from the infusion site within the muscle during rest, exercise and recovery was determined. Microdialysis was performed...... in thigh muscles (vastus lateralis muscle) in six healthy men. One of the microdialysis catheters was used to block prostaglandin synthesis by infusion of the NSAID indomethacin. Additional catheters were placed 1 and 4 cm away from the infusion and in the contralateral leg (working control). Following 2 h...

Lipids and addiction: how sex steroids, prostaglandins, and cannabinoids interact with drugs of abuse.

Science.gov (United States)

Leishman, Emma; Kokesh, Kevin J; Bradshaw, Heather B

2013-04-01

Lipidomics aims to identify and characterize all endogenous species of lipids and understand their roles in cellular signaling and, ultimately, the functioning of the organism. We are on the cusp of fully understanding the functions of many of the lipid signaling systems that have been identified for decades (e.g., steroids, prostaglandins), whereas our understanding of newer lipid signaling systems (e.g., endocannabinoids, N-acyl amides) still lags considerably behind. With an emphasis on their roles in the neurophysiology of addiction, we will examine three classes of lipids--sex steroids, prostaglandins, and cannabinoids--and how they work synergistically in the neurocircuitry of motivation. We will first give a brief overview of the biosynthesis for each class of lipid and its receptors, and then summarize what is known about the collective roles of the lipids in cocaine and alcohol abuse. This approach provides a novel view of lipid signaling as a class of molecules and their synergistic roles in addiction. © 2013 New York Academy of Sciences.

Minimum deltaV Burn Planning for the International Space Station Using a Hybrid Optimization Technique, Level 1

Science.gov (United States)

Brown, Aaron J.

2015-01-01

The International Space Station's (ISS) trajectory is coordinated and executed by the Trajectory Operations and Planning (TOPO) group at NASA's Johnson Space Center. TOPO group personnel routinely generate look-ahead trajectories for the ISS that incorporate translation burns needed to maintain its orbit over the next three to twelve months. The burns are modeled as in-plane, horizontal burns, and must meet operational trajectory constraints imposed by both NASA and the Russian Space Agency. In generating these trajectories, TOPO personnel must determine the number of burns to model, each burn's Time of Ignition (TIG), and magnitude (i.e. deltaV) that meet these constraints. The current process for targeting these burns is manually intensive, and does not take advantage of more modern techniques that can reduce the workload needed to find feasible burn solutions, i.e. solutions that simply meet the constraints, or provide optimal burn solutions that minimize the total DeltaV while simultaneously meeting the constraints. A two-level, hybrid optimization technique is proposed to find both feasible and globally optimal burn solutions for ISS trajectory planning. For optimal solutions, the technique breaks the optimization problem into two distinct sub-problems, one for choosing the optimal number of burns and each burn's optimal TIG, and the other for computing the minimum total deltaV burn solution that satisfies the trajectory constraints. Each of the two aforementioned levels uses a different optimization algorithm to solve one of the sub-problems, giving rise to a hybrid technique. Level 2, or the outer level, uses a genetic algorithm to select the number of burns and each burn's TIG. Level 1, or the inner level, uses the burn TIGs from Level 2 in a sequential quadratic programming (SQP) algorithm to compute a minimum total deltaV burn solution subject to the trajectory constraints. The total deltaV from Level 1 is then used as a fitness function by the genetic

Separation of prostaglandin metabolites on sephadex LH 20 columns

DEFF Research Database (Denmark)

Hansen, Harald S.; Bukhave, K.

1978-01-01

Sephadex LH 20 columns have been investigated for the separation of initial prostaglandin metabolites. Solvent systems are described for the separation of the free acids of 15-keto-dihydro-PGE, 15-keto-PGE, PGE, and PGF(1a). Further, one of the solvent systems is described for the separation...

Role of contractile prostaglandins and Rho-kinase in growth factor-induced airway smooth muscle contraction

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Zaagsma Johan

2005-07-01

Full Text Available Abstract Background In addition to their proliferative and differentiating effects, several growth factors are capable of inducing a sustained airway smooth muscle (ASM contraction. These contractile effects were previously found to be dependent on Rho-kinase and have also been associated with the production of eicosanoids. However, the precise mechanisms underlying growth factor-induced contraction are still unknown. In this study we investigated the role of contractile prostaglandins and Rho-kinase in growth factor-induced ASM contraction. Methods Growth factor-induced contractions of guinea pig open-ring tracheal preparations were studied by isometric tension measurements. The contribution of Rho-kinase, mitogen-activated protein kinase (MAPK and cyclooxygenase (COX to these reponses was established, using the inhibitors Y-27632 (1 μM, U-0126 (3 μM and indomethacin (3 μM, respectively. The Rho-kinase dependency of contractions induced by exogenously applied prostaglandin F2α (PGF2α and prostaglandin E2 (PGE2 was also studied. In addition, the effects of the selective FP-receptor antagonist AL-8810 (10 μM and the selective EP1-antagonist AH-6809 (10 μM on growth factor-induced contractions were investigated, both in intact and epithelium-denuded preparations. Growth factor-induced PGF2α-and PGE2-release in the absence and presence of Y-27632, U-0126 and indomethacin, was assessed by an ELISA-assay. Results Epidermal growth factor (EGF-and platelet-derived growth factor (PDGF-induced contractions of guinea pig tracheal smooth muscle preparations were dependent on Rho-kinase, MAPK and COX. Interestingly, growth factor-induced PGF2α-and PGE2-release from tracheal rings was significantly reduced by U-0126 and indomethacin, but not by Y-27632. Also, PGF2α-and PGE2-induced ASM contractions were largely dependent on Rho-kinase, in contrast to other contractile agonists like histamine. The FP-receptor antagonist AL-8810 (10 μM significantly

15-Deoxy-Delta-12,14-Prostaglandin J2 Inhibits Lung Inflammation and Remodeling in Distinct Murine Models of Asthma

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Diego S. Coutinho

2017-06-01

Full Text Available 15-deoxy-Δ-12,14-prostaglandin J2 (15d-PGJ2 has been described as an anti-inflammatory lipid mediator in several in vitro and in vivo studies, but its effect on allergic pulmonary inflammation remains elusive. The aim of this study was to investigate the therapeutic potential of 15d-PGJ2 based on distinct murine models of allergic asthma triggered by either ovalbumin (OVA or house dust mite extract (HDM. Characteristics of lung inflammation, airway hyper-reactivity (AHR, mucus exacerbation, and lung remodeling in sensitized A/J mice treated or not with 15d-PGJ2 were assessed. 15d-PGJ2 treatments were carried out systemically or topically given via subcutaneous injection or intranasal instillation, respectively. Analyses were carried out 24 h after the last allergen provocation. Irrespective of the route of administration, 15d-PGJ2 significantly inhibited the peribronchial accumulation of eosinophils and neutrophils, subepithelial fibrosis and also mucus exacerbation caused by either OVA or HDM challenge. The protective effect of 15d-PGJ2 occurred in parallel with inhibition of allergen-induced AHR and lung tissue production of pro-inflammatory cytokines, such as interleukin (IL-5, IL-13, IL-17, and TNF-α. Finally, 15d-PGJ2 was found effective in inhibiting NF-κB phosphorylation upon HDM challenge as measured by Western blotting. In conclusion, our findings suggest that 15d-PGJ2 can reduce crucial features of asthma, including AHR, lung inflammation, and remodeling in distinct murine models of the disease. These effects are associated with a decrease in lung tissue generation of pro-inflammatory cytokines by a mechanism related to downregulation of NF-κB phosphorylation.

The effects of prostaglandin E2 in growing rats - Increased metaphyseal hard tissue and cortico-endosteal bone formation

Science.gov (United States)

Jee, W. S. S.; Ueno, K.; Deng, Y. P.; Woodbury, D. M.

1985-01-01

The role of in vivo prostaglandin E2 (PGE2) in bone formation is investigated. Twenty-five male Sprague-Dawley rats weighing between 223-267 g were injected subcutaneously with 0.3, 1.0, 3.0, and 6.0 mg of PGE2-kg daily for 21 days. The processing of the tibiae for observation is described. Radiographs and histomorphometric analyses are also utilized to study bone formation. Body weight, weights of soft tissues and bones morphometry are evaluated. It is observed that PGE2 depressed longitudinal bone growth, increased growth cartilage thickness, decreased degenerative cartilage cell size and cartilage cell production, and significantly increased proximal tibial metaphyseal hard tissue mass. The data reveal that periosteal bone formation is slowed down at higher doses of PGE2 and endosteal bone formation is slightly depressed less than 10 days post injection; however, here is a late increase (10 days after post injection) in endosteal bone formation and in the formation of trabecular bone in the marrow cavity of the tibial shaft. It is noted that the effects of PGE2 on bone formation are similar to the responses of weaning rats to PGE2.

Induction of labour by extra-amniotic prostaglandins.

Science.gov (United States)

Miller, A W; Mack, D S

1974-09-01

Extraamniotic administration of prostaglandins (PGs) for labor induction was studied. 69 patients took part in this study, 43 of whom were primigravid and 26 of whom were parous. 65 of the cases had a normally developed child and 4 fetuses were known to be anencephalic. Pregnancy maturity ranged from 26-41 weeks. PGE2 was administered as for midtrimester abortion, except that a catheter with a balloon capacity of 30-50 ml was used. PGE2 concentration of 50, 75, or 100 mcg/ml was infused continuously by a Palmer pump at a rate of 1.8 ml per hour. Labor was successfully induced in all cases, judging by the establishment of regular uterine activity and softening, effacement, and dilatation of the cervix. Mean time of PG infusion was 6.5 hours. Mean dose was .9 mg. Oxytocin was used as a supplement if necessary, and 3 of 4 women with anencephalic fetuses needed oxytocin treatment. 39% of primigravida required oxytocin, and 17% of parous women did. Mean induction-delivery interval in the normal fetus group was 14 hours 48 minutes for primigravida, and was 9 hours 35 minutes in parous women. 12 patients were delivered by Caesarean section. 3 of the 65 normal fetuses died during labor. Uterine hypertonus occurred in 1 mother. PGE2 is indicated for labor induction when avoidance of artificial rupture of membranes is wanted.

Effect of resveratrol on 17beta-estradiol sulfation by human hepatic and jejunal S9 and recombinant sulfotransferase 1E1.

Science.gov (United States)

Furimsky, Anna M; Green, Carol E; Sharp, Lewanne E Hunt; Catz, Paul; Adjei, Araba A; Parman, Toufan; Kapetanovic, Izet M; Weinshilboum, Richard M; Iyer, Lalitha V

2008-01-01

The purpose of this study was to investigate the sulfation of resveratrol (3,5,4'-trihydroxystilbene) and its potential to exhibit drug-drug interactions via sulfation. The possible interaction of resveratrol with 17beta-estradiol (E2), a major estrogen hormone and prototypic substrate for sulfate conjugation, was studied. Resveratrol and E2 are both known to undergo sulfate conjugation catalyzed by human sulfotransferases (SULTs). Resveratrol is a phytoestrogen with mixed estrogen agonist/antagonist properties that is being developed as a chemopreventive agent. The sulfate conjugation of E2 and resveratrol were studied individually using S9 fractions from human liver and jejunum as well as recombinant human SULT isoforms. The sulfation of E2 (3-20 nM) was then investigated in the presence of various concentrations (0, 0.5, 1, and 2 microM) of resveratrol using the two S9 preparations as well as recombinant SULT1E1, the major isoform responsible for E2 sulfation. Resveratrol inhibited E2 sulfation with estimated K(i) values of 1.1 microM (liver), 0.6 microM (jejunum), and 2.3 microM (SULT1E1), concentrations that could be pharmacologically relevant. The results suggest that these phytoestrogens can potentially alter the homeostasis of estrogen levels. These findings also imply that resveratrol may inhibit the metabolism of other estrogen analogs or therapeutic agents such as ethinylestradiol or dietary components that are also substrates for SULT1E1.

Groundwater geochemistry of nile delta-desert interface 1.isotope hydrology

International Nuclear Information System (INIS)

Hussein, M.F.; Nada, A.A.; Awad, M.A.

1995-01-01

Sustenance and environmental protection of groundwater supply is of major concern in the integral environmental development in the arid to sub-arid regions in the Nile basin. Isotope data ( 18O , 2H and 3H ) of groundwater in the west of the Nile delta indicates the contribution of palaeo groundwater component (in the range 0.1 - 0.8 with means of 0.39 and 0.52 for tahrir and khatatbah, respectively) along with sub recent recharge from the delta aquifer and recent recharge from irrigation conveyance canals in desert. Isotope mixing model (developed as Two-input table using excel TM spreads heat on apple Macintosh TM) is proposed to explain the apparent discrepancies in groundwater isotopic composition of khatatbah and tahrir areas assuming the contribution of two isotopically different palaeo-oples with two isotopically similar maind delta groundwater poles. About 0.30% 1 8 O depletion per 10 Km downstream is detected and low northward groundwater recharge is suggested along 75 Km of the western strip of rosetta Nile. Higher sub-recent recharge from the main delta aquifer is believed to take place in khatatbah than tahrir whereas the last is believed to be replenished at present from the irrigation/ drainage network and irrigated fields with higher pollution risk for groundwater system in tahrir aquifer is exposed to northern marine intrusion. Lowering of the piezo metric level is to be expected in the newly exploited desertic areas under over pumping. 9 figs

Curcumin induces apoptosis and inhibits prostaglandin E(2) production in synovial fibroblasts of patients with rheumatoid arthritis.

Science.gov (United States)

Park, Cheol; Moon, Dong-Oh; Choi, Il-Whan; Choi, Byung Tae; Nam, Taek-Jeong; Rhu, Chung-Ho; Kwon, Taeg Kyu; Lee, Won Ho; Kim, Gi-Young; Choi, Yung Hyun

2007-09-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease that is characterized by hyperplasia of the synovial fibroblasts, which is partly the result of decreased apoptosis. This study investigated the mechanisms through which curcumin, a polyphenolic compound from the rhizome of Curcuma longa, exerts its anti-proliferative action in the synovial fibroblasts obtained from patients with RA. Exposure of the synovial fibroblasts to curcumin resulted in growth inhibition and the induction of apoptosis, as measured by MTT assay, fluorescent microscopy and Annexin-V-based assay. RT-PCR and immunoblotting showed that treating the cells with curcumin resulted in the down-regulation of anti-apoptotic Bcl-2 and the X-linked inhibitor of the apoptosis protein as well as the up-regulation of pro-apoptotic Bax expression in a concentration-dependent manner. Curcumin-induced apoptosis was also associated with the proteolytic activation of caspase-3 and caspase-9, and the concomitant degradation of poly(ADP-ribose) polymerase protein. Furthermore, curcumin decreased the expression levels of the cyclooxygenase (COX)-2 mRNA and protein without causing significant changes in the COX-1 levels, which was correlated with the inhibition of prostaglandin E(2) synthesis. These results show that curcumin might help identify a new therapeutic pathway against hyperplasia of the synovial fibroblasts in RA.

Measurement of $\\Delta^{++}$(1232) production in hadronic Z decays

CERN Document Server

Abreu, P; Adye, T; Agasi, E; Ajinenko, I; Aleksan, Roy; Alekseev, G D; Allport, P P; Almehed, S; Alvsvaag, S J; Amaldi, Ugo; Amato, S; Andreazza, A; Andrieux, M L; Antilogus, P; Anykeyev, V B; Apel, W D; Arnoud, Y; Åsman, B; Augustin, J E; Augustinus, A; Baillon, Paul; Bambade, P; Barão, F; Barate, R; Bardin, Dimitri Yuri; Barker, G J; Baroncelli, A; Bärring, O; Barrio, J A; Bartl, Walter; Bates, M J; Battaglia, Marco; Baubillier, M; Baudot, J; Becks, K H; Begalli, M; Beillière, P; Belokopytov, Yu A; Benvenuti, Alberto C; Berggren, M; Bertrand, D; Bianchi, F; Bigi, M; Bilenky, S M; Billoir, P; Bloch, D; Blume, M; Blyth, S; Bocci, V; Bolognese, T; Bonesini, M; Bonivento, W; Booth, P S L; Borisov, G; Bosio, C; Bosworth, S; Botner, O; Bouquet, B; Bourdarios, C; Bowcock, T J V; Bozzo, M; Branchini, P; Brand, K D; Brenke, T; Brenner, R A; Bricman, C; Brillault, L; Brown, R C A; Brückman, P; Brunet, J M; Bugge, L; Buran, T; Burgsmüller, T; Buschmann, P; Buys, A; Caccia, M; Calvi, M; Camacho-Rozas, A J; Camporesi, T; Canale, V; Canepa, M; Cankocak, K; Cao, F; Carena, F; Carrilho, P; Carroll, L; Caso, Carlo; Castillo-Gimenez, M V; Cattai, A; Cavallo, F R; Cerrito, L; Chabaud, V; Charpentier, P; Chaussard, L; Chauveau, J; Checchia, P; Chelkov, G A; Chierici, R; Chliapnikov, P V; Chochula, P; Chorowicz, V; Cindro, V; Collins, P; Contreras, J L; Contri, R; Cortina, E; Cosme, G; Cossutti, F; Crawley, H B; Crennell, D J; Crosetti, G; Cuevas-Maestro, J; Czellar, S; Dahl-Jensen, Erik; Dahm, J; D'Almagne, B; Dam, M; Damgaard, G; Daum, A; Dauncey, P D; Davenport, Martyn; Da Silva, W; Defoix, C; Della Ricca, G; Delpierre, P A; Demaria, N; De Angelis, A; De Boeck, H; de Boer, Wim; De Brabandere, S; De Clercq, C; La Vaissière, C de; De Lotto, B; De Min, A; De Paula, L S; De Saint-Jean, C; Dijkstra, H; Di Ciaccio, Lucia; Djama, F; Dolbeau, J; Dönszelmann, M; Doroba, K; Dracos, M; Drees, J; Drees, K A; Dris, M; Dufour, Y; Dupont, F; Edsall, D M; Ehret, R; Eigen, G; Ekelöf, T J C; Ekspong, Gösta; Elsing, M; Engel, J P; Ershaidat, N; Erzen, B; Espirito-Santo, M C; Falk, E; Fassouliotis, D; Feindt, Michael; Ferrer, A; Filippas-Tassos, A; Firestone, A; Fischer, P A; Föth, H; Fokitis, E; Fontanelli, F; Formenti, F; Franek, B J; Frenkiel, P; Fries, D E C; Frodesen, A G; Frühwirth, R; Fulda-Quenzer, F; Fuster, J A; Galloni, A; Gamba, D; Gandelman, M; García, C; García, J; Gaspar, C; Gasparini, U; Gavillet, P; Gazis, E N; Gelé, D; Gerber, J P; Gibbs, M; Gokieli, R; Golob, B; Gopal, Gian P; Gorn, L; Górski, M; Guz, Yu; Gracco, Valerio; Graziani, E; Grosdidier, G; Gunnarsson, P; Günther, M; Guy, J; Haedinger, U; Hahn, F; Hahn, M; Hahn, S; Hajduk, Z; Hallgren, A; Hamacher, K; Hao, W; Harris, F J; Hedberg, V; Henriques, R P; Hernández, J J; Herquet, P; Herr, H; Hessing, T L; Higón, E; Hilke, Hans Jürgen; Hill, T S; Holmgren, S O; Holt, P J; Holthuizen, D J; Houlden, M A; Hrubec, Josef; Huet, K; Hultqvist, K; Ioannou, P; Jackson, J N; Jacobsson, R; Jalocha, P; Janik, R; Jarlskog, G; Jarry, P; Jean-Marie, B; Johansson, E K; Jönsson, L B; Jönsson, P E; Joram, Christian; Juillot, P; Kaiser, M; Kapusta, F; Karlsson, M; Karvelas, E; Katsanevas, S; Katsoufis, E C; Keränen, R; Khomenko, B A; Khovanskii, N N; King, B J; Kjaer, N J; Klein, H; Klovning, A; Kluit, P M; Köhne, J H; Köne, B; Kokkinias, P; Koratzinos, M; Kostyukhin, V; Kourkoumelis, C; Kuznetsov, O; Kramer, P H; Krammer, Manfred; Kreuter, C; Królikowski, J; Kronkvist, I J; Krumshtein, Z; Krupinski, W; Kubinec, P; Kucewicz, W; Kurvinen, K L; Lacasta, C; Laktineh, I; Lamblot, S; Lamsa, J; Lanceri, L; Lane, D W; Langefeld, P; Lapin, V; Last, I; Laugier, J P; Lauhakangas, R; Leder, Gerhard; Ledroit, F; Lefébure, V; Legan, C K; Leitner, R; Lemoigne, Y; Lemonne, J; Lenzen, Georg; Lepeltier, V; Lesiak, T; Liko, D; Lindner, R; Lipniacka, A; Lippi, I; Lörstad, B; Lokajícek, M; Loken, J G; López, J M; López-Fernandez, A; López-Aguera, M A; Loukas, D; Lutz, P; Lyons, L; Maehlum, G; Maio, A; Malychev, V; Mandl, F; Marco, J; Maréchal, B; Margoni, M; Marin, J C; Mariotti, C; Markou, A; Maron, T; Martínez-Rivero, C; Martínez-Vidal, F; Martí i García, S; Matorras, F; Matteuzzi, C; Matthiae, Giorgio; Mazzucato, M; McCubbin, M L; McKay, R; McNulty, R; Medbo, J; Meroni, C; Meyer, W T; Michelotto, M; Migliore, E; Mirabito, L; Mitaroff, Winfried A; Mjörnmark, U; Moa, T; Møller, R; Mönig, K; Monge, M R; Morettini, P; Müller, H; Mundim, L M; Murray, W J; Muryn, B; Myatt, Gerald; Naraghi, F; Navarria, Francesco Luigi; Navas, S; Negri, P; Némécek, S; Neumann, W; Neumeister, N; Nicolaidou, R; Nielsen, B S; Nieuwenhuizen, M; Nikolaenko, V; Niss, P; Nomerotski, A; Normand, Ainsley; Oberschulte-Beckmann, W; Obraztsov, V F; Olshevskii, A G; Onofre, A; Orava, Risto; Österberg, K; Ouraou, A; Paganini, P; Paganoni, M; Pagès, P; Palka, H; Papadopoulou, T D; Pape, L; Parkes, C; Parodi, F; Passeri, A; Pegoraro, M; Pernegger, H; Pernicka, Manfred; Perrotta, A; Petridou, C; Petrolini, A; Phillips, H T; Piana, G; Pierre, F; Pimenta, M; Pindo, M; Plaszczynski, S; Podobrin, O; Pol, M E; Polok, G; Poropat, P; Pozdnyakov, V; Prest, M; Privitera, P; Pukhaeva, N; Pullia, Antonio; Radojicic, D; Ragazzi, S; Rahmani, H; Rames, J; Ratoff, P N; Read, A L; Reale, M; Rebecchi, P; Redaelli, N G; Regler, Meinhard; Reid, D; Renton, P B; Resvanis, L K; Richard, F; Richardson, J; Rídky, J; Rinaudo, G; Ripp, I; Romero, A; Roncagliolo, I; Ronchese, P; Roos, L; Rosenberg, E I; Rosso, E; Roudeau, Patrick; Rovelli, T; Rückstuhl, W; Ruhlmann-Kleider, V; Ruiz, A; Rybicki, K; Rybin, A; Saarikko, H; Sacquin, Yu; Sadovskii, A; Sajot, G; Salt, J; Sánchez, J; Sannino, M; Schneider, H; Schyns, M A E; Sciolla, G; Scuri, F; Seager, P; Sedykh, Yu; Segar, A M; Seitz, A; Sekulin, R L; Shellard, R C; Siccama, I; Siegrist, P; Simonetti, S; Simonetto, F; Sissakian, A N; Sitár, B; Skaali, T B; Smadja, G; Smirnova, O G; Smith, G R; Sosnowski, R; Souza-Santos, D; Spassoff, Tz; Spiriti, E; Sponholz, P; Squarcia, S; Stanescu, C; Stapnes, Steinar; Stavitski, I; Stepaniak, K; Stichelbaut, F; Stocchi, A; Strauss, J; Strub, R; Stugu, B; Szczekowski, M; Szeptycka, M; Tabarelli de Fatis, T; Tavernet, J P; Chikilev, O G; Tilquin, A; Timmermans, J; Tkatchev, L G; Todorov, T; Toet, D Z; Tomaradze, A G; Tomé, B; Tortora, L; Tranströmer, G; Treille, D; Trischuk, W; Tristram, G; Trombini, A; Troncon, C; Tsirou, A L; Turluer, M L; Tyapkin, I A; Tyndel, M; Tzamarias, S; Überschär, B; Ullaland, O; Uvarov, V; Valenti, G; Vallazza, E; Van der Velde, C; van Apeldoorn, G W; van Dam, P; Van Doninck, W K; Van Eldik, J; Vassilopoulos, N; Vegni, G; Ventura, L; Venus, W A; Verbeure, F; Verlato, M; Vertogradov, L S; Vilanova, D; Vincent, P; Vitale, L; Vlasov, E; Vodopyanov, A S; Vrba, V; Wahlen, H; Walck, C; Waldner, F; Weierstall, M; Weilhammer, Peter; Wetherell, Alan M; Wicke, D; Wickens, J H; Wielers, M; Wilkinson, G R; Williams, W S C; Winter, M; Witek, M; Woschnagg, K; Yip, K; Yushchenko, O P; Zach, F; Zacharatou-Jarlskog, C; Zaitsev, A; Zalewska-Bak, A; Zalewski, Piotr; Zavrtanik, D; Zevgolatakos, E; Zhigunov, V P; Zimin, N I; Zito, M; Zontar, D; Zuberi, R; Zucchelli, G C; Zumerle, G

1995-01-01

A measurement of the \\Delta^{++}(1232) inclusive production in hadronic decays of the Z at LEP is presented, based on 1.3 million hadronic events collected~ by the DELPHI~ detector in the 1994 LEP running~ period. The DELPHI ring imaging Cherenkov counters are used for identifying hadrons. The average \\Delta^{++}(1232) multiplicity per hadronic event is 0.079 \\pm 0.015 which is more than a factor of two below the JETSET, HERWIG and UCLA model predictions. It agrees with a recently proposed universal mass dependence of particle production rates in e^{+}e^- annihilations.

Thermodynamics of the (Sm{sub 2}Fe{sub 17-x}Ga{sub x}+H{sub 2}) system

Energy Technology Data Exchange (ETDEWEB)

Kubis, M.; Handstein, A.; Gebel, B.; Gutfleisch, O.; Mueller, K.H.; Schultz, L. [Institut fuer Festkoerper- und Werkstofforschung Dresden e.V. (Germany). Inst. fuer Metallische Werkstoffe

2000-08-10

Sm{sub 2}Fe{sub 17-x}Ga{sub x} samples (with x=0, 0.5, 1, and 2) were disproportionated into SmH{sub 2} and {alpha}-(Fe,Ga) by heating the samples in 4 MPa hydrogen up to 650 C. It was possible to disproportionate even the more stable compounds with a higher Ga content under these conditions. The recombination into the original 2:17 phase was carried out by annealing in low hydrogen pressures of 2.5, 12 and 60 kPa. The values of the hydride formation enthalpy, {delta}H, and of the change of entropy, {delta}S, for the Sm{sub 2}Fe{sub 17-x}Ga{sub x} compounds were obtained by using the Van't Hoff relation. It was found that the negative {delta}H increases monotonically from 141 to 229 kJ/mol H{sub 2} and the negative {delta}S increases monotonically from 112 to 258 J/Kmol H{sub 2} for x=0 to x=2, respectively. These results show that the higher stability for the compounds with increasing Ga content is mainly attributed to the increasing negative change of entropy -{delta}S and not, as expected before, to a decrease of -{delta}H. (orig.)

Prostaglandin E2 EP2 activation reduces memory decline in R6/1 mouse model of Huntington's disease by the induction of BDNF-dependent synaptic plasticity.

Science.gov (United States)

Anglada-Huguet, Marta; Vidal-Sancho, Laura; Giralt, Albert; García-Díaz Barriga, Gerardo; Xifró, Xavier; Alberch, Jordi

2016-11-01

Huntington's disease (HD) patients and mouse models show learning and memory impairment even before the onset of motor symptoms. Deficits in hippocampal synaptic plasticity have been involved in the HD memory impairment. Several studies show that prostaglandin E2 (PGE2) EP2 receptor stimulates synaptic plasticity and memory formation. However, this role was not explored in neurodegenerative diseases. Here, we investigated the capacity of PGE2 EP2 receptor to promote synaptic plasticity and memory improvements in a model of HD, the R6/1 mice, by administration of the agonist misoprostol. We found that misoprostol increases dendritic branching in cultured hippocampal neurons in a brain-derived neurotrophic factor (BDNF)-dependent manner. Then, we implanted an osmotic mini-pump system to chronically administrate misoprostol to R6/1 mice from 14 to 18weeks of age. We observed that misoprostol treatment ameliorates the R6/1 long-term memory deficits as analyzed by the T-maze spontaneous alternation task and the novel object recognition test. Importantly, administration of misoprostol promoted the expression of hippocampal BDNF. Moreover, the treatment with misoprostol in R6/1 mice blocked the reduction in the number of PSD-95 and VGluT-1 positive particles observed in hippocampus of vehicle-R6/1 mice. In addition, we observed an increase of cAMP levels in the dentate ` of WT and R6/1 mice treated with misoprostol. Accordingly, we showed a reduction in the number of mutant huntingtin nuclear inclusions in the dentate gyrus of R6/1 mice. Altogether, these results suggest a putative therapeutic effect of PGE2 EP2 receptor in reducing cognitive deficits in HD. Copyright © 2016. Published by Elsevier Inc.

High IL-17E and low IL-17C dermal expression identifies a fibrosis-specific motif common to morphea and systemic sclerosis.

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Paola Adele Lonati

Full Text Available BACKGROUND: High interleukin (IL-17A levels are characteristically found in the skin of systemic sclerosis (SSc individuals. Our aim was to investigate whether the dermal expression of IL-17A and related IL-17 family members (i.e. IL-17C, IL-17E and IL-17F could distinguish fibrotic from healthy skin and could show similarities in SSc and morphea, two disorders with presumed distinct pathogenesis, but characterized by skin fibrosis. METHODS: Biopsies were obtained from the involved skin of 14 SSc, 5 morphea and 8 healthy donors (HD undergoing plastic surgery. Immunohistochemistry/immunofluorescence techniques were coupled to a semi-automated imaging quantification approach to determine the presence of the IL-17 family members in the skin. The in vitro effects induced by the IL-17 family members on fibroblasts from normal and SSc individuals were assessed by ELISA and RIA. RESULTS: Positive cells for each of the IL-17 isoforms investigated were present in the dermis of all the individuals tested, though with variable frequencies. SSc individuals had increased frequency of IL-17A+ (p = 0.0237 and decreased frequency of IL-17F+ (p = 0.0127 and IL-17C+ cells (p = 0.0008 when compared to HD. Similarly, morphea individuals had less frequent IL-17C+ cells (p = 0.0186 in their skin but showed similar number of IL-17A+ and IL-17F+ cells when compared to HD. Finally, IL-17E+ cells were more numerous in morphea (p = 0.0109 and tended to be more frequent in SSc than in HD. Fibroblast production of IL-6, MMP-1 and MCP-1 was enhanced in a dose-dependent manner in the presence of IL-17E and IL-17F, but not in the presence of IL-17C. None of the cytokine tested had significant effect on type I collagen production. Of interest, in SSc the frequency of both IL-17A and IL-17F positive cells increased with disease duration. CONCLUSIONS: The frequency of IL-17A and IL-17F distinguish SSc to morphea individuals while dermal expression of IL-17C (low and IL-17E (high

Prostaglandin D2 Receptor DP1 Antibodies Predict Vaccine-induced and Spontaneous Narcolepsy Type 1: Large-scale Study of Antibody Profiling

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Helle Sadam

2018-03-01

Full Text Available Background: Neuropathological findings support an autoimmune etiology as an underlying factor for loss of orexin-producing neurons in spontaneous narcolepsy type 1 (narcolepsy with cataplexy; sNT1 as well as in Pandemrix influenza vaccine-induced narcolepsy type 1 (Pdmx-NT1. The precise molecular target or antigens for the immune response have, however, remained elusive. Methods: Here we have performed a comprehensive antigenic repertoire analysis of sera using the next-generation phage display method - mimotope variation analysis (MVA. Samples from 64 children and adolescents were analyzed: 10 with Pdmx-NT1, 6 with sNT1, 16 Pandemrix-vaccinated, 16 H1N1 infected, and 16 unvaccinated healthy individuals. The diagnosis of NT1 was defined by the American Academy of Sleep Medicine international criteria of sleep disorders v3. Findings: Our data showed that although the immunoprofiles toward vaccination were generally similar in study groups, there were also striking differences in immunoprofiles between sNT1 and Pdmx-NT1 groups as compared with controls. Prominent immune response was observed to a peptide epitope derived from prostaglandin D2 receptor (DP1, as well as peptides homologous to B cell lymphoma 6 protein. Further validation confirmed that these can act as true antigenic targets in discriminating NT1 diseased along with a novel epitope of hemagglutinin of H1N1 to delineate exposure to H1N1. Interpretation: We propose that DP1 is a novel molecular target of autoimmune response and presents a potential diagnostic biomarker for NT1. DP1 is involved in the regulation of non-rapid eye movement (NREM sleep and thus alterations in its functions could contribute to the disturbed sleep regulation in NT1 that warrants further studies. Together our results also show that MVA is a helpful method for finding novel peptide antigens to classify human autoimmune diseases, possibly facilitating the design of better therapies. Keywords: Narcolepsy type 1

Murine FATP alleviates growth and biochemical deficiencies of yeast fat1Delta strains

DEFF Research Database (Denmark)

Dirusso, C C; Connell, E J; Færgeman, Nils J.

2000-01-01

following incubation of the cells with exogenous oleate. Expression of either Fat1p or murine FATP from a plasmid in a fat1Delta strain restored these phenotypic and biochemical deficiencies. Fat1p and FATP restored growth of fat1Delta cells in the presence of cerulenin and under hypoxic conditions....... Furthermore, fatty-acid transport was restored and was found to be chain length specific: octanoate, a medium-chain fatty acid was transported in a Fat1p- and FATP-independent manner while the long-chain fatty acids myristate, palmitate, and oleate required either Fat1p or FATP for maximal levels of transport....... Lignoceryl CoA synthetase activities were restored to wild-type levels in fat1Delta strains expressing either Fat1p or FATP. Fat1p or FATP also restored wild-type levels of beta-oxidation of exogenous long-chain fatty acids. These data show that Fat1p and FATP are functionally equivalent when expressed...

$\\delta$-Expansion at Finite Temperature

OpenAIRE

Ramos, Rudnei O.

1996-01-01

We apply the $\\delta$-expansion perturbation scheme to the $\\lambda \\phi^{4}$ self-interacting scalar field theory in 3+1 D at finite temperature. In the $\\delta$-expansion the interaction term is written as $\\lambda (\\phi^{2})^{ 1 + \\delta}$ and $\\delta$ is considered as the perturbation parameter. We compute within this perturbative approach the renormalized mass at finite temperature at a finite order in $\\delta$. The results are compared with the usual loop-expansion at finite temperature.

O2/1 Delta/ emission in the day and night airglow of Venus

Science.gov (United States)

Connes, P.; Noxon, J. F.; Traub, W. A.; Carleton, N. P.

1979-01-01

An intense airglow from O2(1 Delta) at 1.27 microns on both the light and the dark sides of Venus has been detected by using a ground-based high-resolution Fourier-transform spectrometer. Both dayglow and nightglow are roughly 1,000 times brighter than the visible O2 nightglow found by Veneras 9 and 10 in 1975. The column emission rate of O2(1 Delta) from Venus is close to the rate at which fresh O atoms are produced from photolysis of CO2 on the day side. Formation of O2(1 Delta) is thus a major step in the removal of O atoms from the atmosphere, and dynamical processes must carry these atoms to the night side fast enough to yield a maximum density near 90 km, which is almost constant over the planet.

Efeitos da prostaglandina E1 (PGE1 na gênese de capilares sanguíneos em músculo esquelético isquêmico de ratos: estudo histológico Effects of prostaglandin E1 (PGE1 in the genesis of blood capillaries in rat ischemic skeletal muscle: histological study

Directory of Open Access Journals (Sweden)

Dorival Moreschi Jr.

2007-12-01

Full Text Available CONTEXTO: A angiogênese terapêutica é uma modalidade de tratamento para pacientes com insuficiência arterial crônica que não têm indicação para revascularização direta ou angioplastia e que não tiveram uma resposta satisfatória ao tratamento clínico. Entre as drogas utilizadas para essa finalidade está a prostaglandina E1 (PGE1. OBJETIVO: Estudar os aspectos morfológicos na gênese de capilares sanguíneos em músculo esquelético do membro caudal de ratos submetidos à isquemia sob a ação da PGE1, administrada por via intramuscular (IM ou endovenosa (EV. MÉTODOS: Foram utilizados 48 ratos, linhagem Wistar-UEM, distribuídos aleatoriamente em três grupos de 16, redistribuídos igualmente em dois subgrupos, observados no 7º e 14º dias, sendo um grupo controle onde apenas foi provocada a isquemia no membro, outro com a isquemia e a injeção da PGE1 via IM e outro com a isquemia e a injeção da PGE1 EV. Para análise dos resultados, foram realizadas a coloração com hematoxilina e eosina (HE e coloração imuno-histoquímica. RESULTADOS: Constatou-se um aumento estatisticamente significativo no número de capilares nos subgrupos com o uso da PGE1 IM e EV, através da contagem nos cortes corados com HE. A imunomarcação não foi eficiente para a quantificação dos capilares. CONCLUSÕES: A PGE1, administrada por via IM ou EV, promoveu, após 14 dias de observação, um aumento no número de capilares no músculo esquelético de ratos submetido à isquemia, identificáveis histologicamente com a coloração em HE. A imunocoloração não permitiu estabelecer uma correlação com o aumento de vasos encontrados na coloração com HE.BACKGROUND: Therapeutic angiogenesis is a treatment modality for patients with chronic arterial insufficiency who do not have indication for direct reconstruction or angioplasty and who were not successfully submitted to clinical treatment. Prostaglandin E1 (PGE1 is one of the drugs used for this

Phenotypic expressions of CCR5-Delta 32/Delta 32 homozygosity

NARCIS (Netherlands)

Nguyen, GT; Carrington, M; Beeler, JA; Dean, M; Aledort, LM; Blatt, PM; Cohen, AR; DiMichele, D; Eyster, ME; Kessler, CM; Konkle, B; Leissinger, C; Luban, N; O'Brien, SJ; Goedert, JJ; O'Brien, TR

1999-01-01

Objective: As blockade of CC-chemokine receptor 5 (CCR5) has been proposed as therapy for HIV-1, we examined whether the CCR5-Delta 32/Delta 32 homozygous genotype has phenotypic expressions other than those related to HIV-1. Design: Study subjects were white homosexual men or men with hemophilia

IL17eScan: A Tool for the Identification of Peptides Inducing IL-17 Response

Directory of Open Access Journals (Sweden)

Sudheer Gupta

2017-10-01

Full Text Available IL-17 cytokines are pro-inflammatory cytokines and are crucial in host defense against various microbes. Induction of these cytokines by microbial antigens has been investigated in the case of ischemic brain injury, gingivitis, candidiasis, autoimmune myocarditis, etc. In this study, we have investigated the ability of amino acid sequence of antigens to induce IL-17 response using machine-learning approaches. A total of 338 IL-17-inducing and 984 IL-17 non-inducing peptides were retrieved from Immune Epitope Database. 80% of the data were randomly selected as training dataset and rest 20% as validation dataset. To predict the IL-17-inducing ability of peptides/protein antigens, different sequence-based machine-learning models were developed. The performance of support vector machine (SVM and random forest (RF was compared with different parameters to predict IL-17-inducing epitopes (IIEs. The dipeptide composition-based SVM-model displayed an accuracy of 82.4% with Matthews correlation coefficient = 0.62 at polynomial (t = 1 kernel on 10-fold cross-validation and outperformed RF. Amino acid residues Leu, Ser, Arg, Asn, and Phe and dipeptides LL, SL, LK, IL, LI, NL, LR, FK, SF, and LE are abundant in IIEs. The present tool helps in the identification of IIEs using machine-learning approaches. The induction of IL-17 plays an important role in several inflammatory diseases, and identification of such epitopes would be of great help to the immunologists. It is freely available at http://metagenomics.iiserb.ac.in/IL17eScan/ and http://metabiosys.iiserb.ac.in/IL17eScan/.

Skn-1a/Oct-11 and {Delta}Np63{alpha} exert antagonizing effects on human keratin expression

Energy Technology Data Exchange (ETDEWEB)

Lena, Anna Maria; Cipollone, Rita; Amelio, Ivano; Catani, Maria Valeria; Ramadan, Safaa [Biochemistry IDI-IRCCS Laboratory and Department of Experimental Medicine and Biochemical Sciences, University of Rome ' Tor Vergata' , 00133, Rome (Italy); Browne, Gareth [MRC Toxicology Unit, Leicester University, Leicester LE1 9HN (United Kingdom); Melino, Gerry [Biochemistry IDI-IRCCS Laboratory and Department of Experimental Medicine and Biochemical Sciences, University of Rome ' Tor Vergata' , 00133, Rome (Italy); MRC Toxicology Unit, Leicester University, Leicester LE1 9HN (United Kingdom); Candi, Eleonora, E-mail: candi@uniroma2.it [Biochemistry IDI-IRCCS Laboratory and Department of Experimental Medicine and Biochemical Sciences, University of Rome ' Tor Vergata' , 00133, Rome (Italy)

2010-10-29

Research highlights: {yields} Skn-1a markedly downregulates {Delta}Np63-driven K14 expression. {yields} {Delta}Np63 inhibits Skn-1a-mediated K10 expression. {yields} {Delta}Np63, mutated in SAM domain, is less effecting in K10 downregulation. {yields} Immunolocalization in human skin of the two transcription factors is partially overlapping. {yields} The antagonistic effects of Skn-1a and p63 is through competition for overlapping responsive elements or through an indirect interaction. -- Abstract: The formation of a stratified epidermis requires a carefully controlled balance between keratinocyte proliferation and differentiation. Here, we report the reciprocal effect on keratin expression of {Delta}Np63, pivotal in normal epidermal morphogenesis and maintenance, and Skn-1a/Oct-11, a POU transcription factor that triggers and regulates the differentiation of keratinocytes. The expression of Skn-1a markedly downregulated {Delta}Np63-driven K14 expression in luciferase reporter assays. The extent of downregulation was comparable to the inhibition of Skn-1a-mediated K10 expression upon expression of {Delta}Np63. {Delta}Np63, mutated in the protein-protein interaction domain (SAM domain; mutated in human ectodermal dysplasia syndrome), was significantly less effecting in downregulating K10, raising the possibility of a direct interaction among Skn-1a and {Delta}Np63. Immunolocalization in human skin biopsies revealed that the expression of the two transcription factors is partially overlapping. Co-immunoprecipitation experiments did not, however, demonstrate a direct interaction between {Delta}Np63 and Skn-1a, suggesting that the antagonistic effects of Skn-1a and p63 on keratin promoter transactivation is probably through competition for overlapping binding sites on target gene promoter or through an indirect interaction.

Groundwater geochemistry of nile delta-desert interface 1.isotope hydrology

Energy Technology Data Exchange (ETDEWEB)

Hussein, M F [Cairo University, Dept., of Soil and water, Giza, Gamma Street, (Egypt); Nada, A A; Awad, M A [Atomic Energy Authority, Nuclear Chemistry Dept., P.o. Box 13759, Cairo, (Egypt)

1995-10-01

Sustenance and environmental protection of groundwater supply is of major concern in the integral environmental development in the arid to sub-arid regions in the Nile basin. Isotope data ({sup 18O}, {sup 2H} and {sup 3H}) of groundwater in the west of the Nile delta indicates the contribution of palaeo groundwater component (in the range 0.1 - 0.8 with means of 0.39 and 0.52 for tahrir and khatatbah, respectively) along with sub recent recharge from the delta aquifer and recent recharge from irrigation conveyance canals in desert. Isotope mixing model (developed as Two-input table using excel{sup TM} spreads heat on apple Macintosh{sup TM)} is proposed to explain the apparent discrepancies in groundwater isotopic composition of khatatbah and tahrir areas assuming the contribution of two isotopically different palaeo-oples with two isotopically similar maind delta groundwater poles. About 0.30% {sup 1}8{sup O} depletion per 10 Km downstream is detected and low northward groundwater recharge is suggested along 75 Km of the western strip of rosetta Nile. Higher sub-recent recharge from the main delta aquifer is believed to take place in khatatbah than tahrir whereas the last is believed to be replenished at present from the irrigation/ drainage network and irrigated fields with higher pollution risk for groundwater system in tahrir aquifer is exposed to northern marine intrusion. Lowering of the piezo metric level is to be expected in the newly exploited desertic areas under over pumping. 9 figs.

Structural studies of {delta}-endotoxin Cry 1 C from Bacillus thuringiensis

Energy Technology Data Exchange (ETDEWEB)

Guimaraes, B.G.; Garratt, R.C.; Oliva, G. [Sao Paulo Univ., Sao Carlos, SP (Brazil). Inst. de Fisica; Lemos, M.V.F. [UNESP, Jaboticabal, SP (Brazil). Dept. de Biologia Aplicada Agropecuaria; Arantes, O.M.N. [Universidade Estadual de Londrina, PR (Brazil). Dept. de Biologia Geral

1996-12-31

Full text. The {delta}-endotoxins are a family of crystal protein by a soil bacterium, Bacillus thuringiensis. The study of these proteins has been of great interest due to their highly specific activity against insects of the orders Lepidoptera, Diptera and Coleoptera. Thus, the {delta}a-endotoxins have been used for more than two decades as biological insecticides to control agricultural pests and, more recently, insects vectors of some diseases. The knowledge of their three-dimensional structures is very important to understand their mechanism of action and their high specificity. To date, the structure of only three proteins of the {delta}-endotoxins family have been reported: Cry3A, a coleopteran-specific toxin (beetle toxin){sup 1}, Cry1Aa, a lepidopteran-specific toxin (butterfly toxin){sup 2} and CytB, a dipteran-specific toxin (mosquito toxin){sup 3} Our work is aimed at the determination of the crystallographic structure by X-ray diffraction of {delta}-endotoxin Cry1C, also toxic to insects of the Lepidoptera order but towards families other than those affected by Cry1Aa. A comparison between these structures may lead to important conclusions about the reasons for the specificity and would allow the planning of mutants with more efficient activity. The cry1C gene was cloned into an adequate vector and expressed in an acrystalliferous B. thuringiensis strain. After cell culture and sporulation the microcrystals of Cry1C were separated by ultra-centrifugation in sacharose. The protoxin inclusion bodies were activated by commercial trpsin and the protease-resistant core was purified by anion-exchange chromatography. Crystallization experiments are being conducted in order to obtain single crystals suitable for diffraction measurements. We intend to use the Protein Crystallograph Station of the LNLS to collect data as soon as it is available and we have suitable crystals. (author) 3 refs.

The effects of photosensitizing antibiotics and ultraviolet irradiation on the biosynthesis of prostaglandins

International Nuclear Information System (INIS)

Lord, J.T.; Ziboh, V.A.; Blick, G.; Poitier, J.; Kursunoglu, I.; Penneys, N.S.

1978-01-01

Oxygenation of arachidonic acid in vitro by calf skin microsomal acetone powder was enhanced by UV-irradiation at wavelengths of 254 and 360 nm. Further enhancement of the oxygenation reaction was observed in the presence of two photosensitizing cyclic antibiotics, tetracycline and demethylchlortetracycline. To test whether or not the oxygenation of arachidonic acid was related to the biosynthesis of prostaglandins, [I- 14 C]-arachidonic acid was incubated with calf skin acetone powder in the presence of UV-irradiation and the cyclic antibiotics. Prostaglandin biosynthesis from arachidonic acid by the calf skin microsomal acetone powder was enhanced after exposure to UV-irradiation at 254 nm and moderately at 360 nm. Incubation in the presence of demethylchlortetra-cycline (0.2 mM) increased prostaglandin biosynthesis approximately 95% over control by UV-irradiation at 254 nm. No significant stimulation of prostaglandin biosynthesis was observed at 360 nm. Non-photosensitizing antibiotics had no effect either on the oxygenation of arachidonic acid or on the biosynthesis of prostaglandin with or without UV-irradiation. It is suggested that the inflammatory reactions associated with these photo-reactive antibiotics may in part, be via the biosynthesis and release of the prostaglandins which are known to produce cutaneous inflammatory reactions. (author)

Intestinal tumor suppression in ApcMin/+ mice by prostaglandin D2 receptor PTGDR

International Nuclear Information System (INIS)

Tippin, Brigette L; Kwong, Alan M; Inadomi, Michael J; Lee, Oliver J; Park, Jae Man; Materi, Alicia M; Buslon, Virgilio S; Lin, Amy M; Kudo, Lili C; Karsten, Stanislav L; French, Samuel W; Narumiya, Shuh; Urade, Yoshihiro; Salido, Eduardo; Lin, Henry J

2014-01-01

Our earlier work showed that knockout of hematopoietic prostaglandin D synthase (HPGDS, an enzyme that produces prostaglandin D 2 ) caused more adenomas in Apc Min/+ mice. Conversely, highly expressed transgenic HPGDS allowed fewer tumors. Prostaglandin D 2 (PGD 2 ) binds to the prostaglandin D 2 receptor known as PTGDR (or DP1). PGD 2 metabolites bind to peroxisome proliferator-activated receptor γ (PPARG). We hypothesized that Ptgdr or Pparg knockouts may raise numbers of tumors, if these receptors take part in tumor suppression by PGD 2 . To assess, we produced Apc Min/+ mice with and without Ptgdr knockouts (147 mice). In separate experiments, we produced Apc Min/+ mice expressing transgenic lipocalin-type prostaglandin D synthase (PTGDS), with and without heterozygous Pparg knockouts (104 mice). Homozygous Ptgdr knockouts raised total numbers of tumors by 30–40% at 6 and 14 weeks. Colon tumors were not affected. Heterozygous Pparg knockouts alone did not affect tumor numbers in Apc Min/+ mice. As mentioned above, our Pparg knockout assessment also included mice with highly expressed PTGDS transgenes. Apc Min/+ mice with transgenic PTGDS had fewer large adenomas (63% of control) and lower levels of v-myc avian myelocytomatosis viral oncogene homolog (MYC) mRNA in the colon. Heterozygous Pparg knockouts appeared to blunt the tumor-suppressing effect of transgenic PTGDS. However, tumor suppression by PGD 2 was more clearly mediated by receptor PTGDR in our experiments. The suppression mechanism did not appear to involve changes in microvessel density or slower proliferation of tumor cells. The data support a role for PGD 2 signals acting through PTGDR in suppression of intestinal tumors

Formation of conjugated delta8,delta10-double bonds by delta12-oleic-acid desaturase-related enzymes: biosynthetic origin of calendic acid.

Science.gov (United States)

Cahoon, E B; Ripp, K G; Hall, S E; Kinney, A J

2001-01-26

Divergent forms of the plant Delta(12)-oleic-acid desaturase (FAD2) have previously been shown to catalyze the formation of acetylenic bonds, epoxy groups, and conjugated Delta(11),Delta(13)-double bonds by modification of an existing Delta(12)-double bond in C(18) fatty acids. Here, we report a class of FAD2-related enzymes that modifies a Delta(9)-double bond to produce the conjugated trans-Delta(8),trans-Delta(10)-double bonds found in calendic acid (18:3Delta(8trans,10trans,12cis)), the major component of the seed oil of Calendula officinalis. Using an expressed sequence tag approach, cDNAs for two closely related FAD2-like enzymes, designated CoFADX-1 and CoFADX-2, were identified from a C. officinalis developing seed cDNA library. The deduced amino acid sequences of these polypeptides share 40-50% identity with those of other FAD2 and FAD2-related enzymes. Expression of either CoFADX-1 or CoFADX-2 in somatic soybean embryos resulted in the production of calendic acid. In embryos expressing CoFADX-2, calendic acid accumulated to as high as 22% (w/w) of the total fatty acids. In addition, expression of CoFADX-1 and CoFADX-2 in Saccharomyces cerevisiae was accompanied by calendic acid accumulation when induced cells were supplied exogenous linoleic acid (18:2Delta(9cis,12cis)). These results are thus consistent with a route of calendic acid synthesis involving modification of the Delta(9)-double bond of linoleic acid. Regiospecificity for Delta(9)-double bonds is unprecedented among FAD2-related enzymes and further expands the functional diversity found in this family of enzymes.

Partial protective effect of CCR5-Delta 32 heterozygosity in a cohort of heterosexual Italian HIV-1 exposed uninfected individuals

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Cauda Roberto

2006-09-01

Full Text Available Abstract Despite multiple sexual exposure to HIV-1 virus, some individuals remain HIV-1 seronegative (exposed seronegative, ESN. The mechanisms underlying this resistance remain still unclear, although a multifactorial pathogenesis can be hypothesised. Although several genetic factors have been related to HIV-1 resistance, the homozigosity for a mutation in CCR5 gene (the 32 bp deletion, i.e. CCR5-Delta32 allele is presently considered the most relevant one. In the present study we analysed the genotype at CCR5 locus of 30 Italian ESN individuals (case group who referred multiple unprotected heterosexual intercourse with HIV-1 seropositive partner(s, for at least two years. One hundred and twenty HIV-1 infected patients and 120 individuals representative of the general population were included as control groups. Twenty percent of ESN individuals had heterozygous CCR5-Delta 32 genotype, compared to 7.5% of HIV-1 seropositive and 10% of individuals from the general population, respectively. None of the analysed individuals had CCR5-Delta 32 homozygous genotype. Sequence analysis of the entire open reading frame of CCR5 was performed in all ESN subjects and no polymorphisms or mutations were identified. Moreover, we determined the distribution of C77G variant in CD45 gene, which has been previously related to HIV-1 infection susceptibility. The frequency of the C77G variant showed no significant difference between ESN subjects and the two control groups. In conclusion, our data show a significantly higher frequency of CCR5-Delta 32 heterozygous genotype (p = 0.04 among the Italian heterosexual ESN individuals compared to HIV-1 seropositive patients, suggesting a partial protective role of CCR5-Delta 32 heterozygosity in this cohort.

Delta Morphodynamics Matters! Ecosystem Services, Poverty and Morphodynamic Change in the Ganges-Brahmaputra Mega-Delta

Science.gov (United States)

Nicholls, R. J.; Adger, N.; Allan, A.; Darby, S. E.; Hutton, C.; Matthews, Z.; Rahman, M.; Whitehead, P. G.; Wolf, J.

2013-12-01

The world's deltas are probably the most vulnerable type of coastal environment, and they face multiple stresses in the coming decades. These stresses include, amongst others, local drivers due to land subsidence, population growth and urbanisation within the deltas, regional drivers due to changes in catchment management (e.g. upstream land use and dam construction), as well as global climate change impacts such as sea-level rise. At the same time, the ecosystem services of river deltas support high population densities, with around 14% of the global population inhabiting deltas. A large proportion of these people experience extremes of poverty and they are therefore severely exposed to vulnerability from environmental and ecological stress and degradation. In areas close to or below the poverty boundary, both subsistence and cash elements of the economy tend to rely disproportionately heavily on ecosystem services which underpin livelihoods. Therefore, to sustainably manage delta environments they must be viewed as complex social-environmental systems where change is only partially driven by physical drivers such as sea level rise and climate change, and human-induced development activities are also critical. Here we outline a new conceptual framework for the development of methods to understand and characterise the key drivers of change in ecosystem services that affect the environment and economic status of populous deltas, focusing specifically on the Ganges-Brahmaputra-Meghna (GBM) mega-delta. The GBM delta is characterised by densely populated coastal lowlands with significant poverty, with livelihoods supported to a large extent by natural ecosystems such as the Sunderbahns (the largest mangrove forest in the world). However, the GBM delta is under severe development pressure due to many growing cities. At present the importance of ecosystems services to poverty and livelihoods is poorly understood. This is due to due to the complexity of interactions

Chemical fingerprinting and diagnostic ratios of Agbada-1 oil spill impacted sites in Niger Delta, Nigeria

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M.C. Onojake

2016-12-01

Full Text Available Detailed compositional analysis by gas chromatography–flame ionization detection (GC–FID was employed to elucidate an oil spill in the Niger delta by fingerprinting technique. Distribution patterns of normal alkanes and isoprenoids show nC8 to nC40 petroleum hydrocarbons. The diagnostic ratios such as Pr/Ph ranged from 1.52 to 2.17; Pr/nC17 ranged from 0.31 to 0.51; Ph/nC18 ranged from 0.14 to 0.99; nC25/nC18 ranged from 0.93 to 3.52; CPI ranged from 0.97 to 1.13; (Pr + nC17/(Ph + nC18 ranged from 1.10 to 2.25; Ph/anth ranged from 0.28 to 1.11; BaA/Ch ranged from 0.57 to 2.90; Fl/Py ranged from 1.24 to 2.90. The ratio Fl/Py which is greater than unity (>1 is an indication of the petrogenic source of PAHs. Statistical analyses such as principal component analysis and cluster analysis were also applied as supporting tools. PCA loadings and scores plots carried out on selected parameters obtained from the analysis of the oil spill show that PC1 and PC2 together represented 95.4% (55.8% and 39.6% respectively of the variability. The high similarity level of the results obtained from the cluster analysis which is 98%, shows that the spilled oil originated from a common source.

Levels of soluble delta-like ligand 1 in the serum and cerebrospinal fluid of tuberculous meningitis patients

Institute of Scientific and Technical Information of China (English)

Jinghong Li; Jinyi Li; Yanjie Jia

2012-01-01

In this study, the levels of soluble delta-like ligand 1 in cerebrospinal fluid and serum of 50 patients with tuberculous meningitis, 30 patients with viral meningitis, 20 patients with purulent meningitis and 40 subjects without central nervous system disease were determined using an enzyme-linked immunosorbent assay. The mean levels of soluble delta-like ligand 1 in both cerebrospinal fluid and serum from patients with tuberculous meningitis were significantly higher compared with those from patients with viral meningitis or purulent meningitis or from subjects without central nervous system disease. Meanwhile, the level of soluble delta-like ligand 1 gradually decreased as tuberculous meningitis patients recovered. If patients deteriorated after treatment, the level of soluble delta-like ligand 1 in cerebrospinal fluid gradually increased. There was no correlation between the level of soluble delta-like ligand 1 and the protein level/cell number in cerebrospinal fluid. Our findings in-dicate that the levels of soluble delta-like ligand 1 in cerebrospinal fluid and serum are reliable markers for the diagnosis of tuberculous meningitis and for monitoring treatment progress. At the same time, this index is not influenced by protein levels or cell numbers in cerebrospinal fluid.

Regional differences in prostaglandin E2 metabolism in human colorectal cancer liver metastases

International Nuclear Information System (INIS)

Young, Alastair L; Chalmers, Claire R; Hawcroft, Gillian; Perry, Sarah L; Treanor, Darren; Toogood, Giles J; Jones, Pamela F; Hull, Mark A

2013-01-01

Prostaglandin (PG) E 2 plays a critical role in colorectal cancer (CRC) progression, including epithelial-mesenchymal transition (EMT). Activity of the rate-limiting enzyme for PGE 2 catabolism (15-hydroxyprostaglandin dehydrogenase [15-PGDH]) is dependent on availability of NAD+. We tested the hypothesis that there is intra-tumoral variability in PGE 2 content, as well as in levels and activity of 15-PGDH, in human CRC liver metastases (CRCLM). To understand possible underlying mechanisms, we investigated the relationship between hypoxia, 15-PGDH and PGE 2 in human CRC cells in vitro. Tissue from the periphery and centre of 20 human CRCLM was analysed for PGE 2 levels, 15-PGDH and cyclooxygenase (COX)-2 expression, 15-PGDH activity, and NAD+/NADH levels. EMT of LIM1863 human CRC cells was induced by transforming growth factor (TGF) β. PGE 2 levels were significantly higher in the centre of CRCLM compared with peripheral tissue (P = 0.04). There were increased levels of 15-PGDH protein in the centre of CRCLM associated with reduced 15-PGDH activity and low NAD+/NADH levels. There was no significant heterogeneity in COX-2 protein expression. NAD+ availability controlled 15-PGDH activity in human CRC cells in vitro. Hypoxia induced 15-PGDH expression in human CRC cells and promoted EMT, in a similar manner to PGE 2 . Combined 15-PGDH expression and loss of membranous E-cadherin (EMT biomarker) were present in the centre of human CRCLM in vivo. There is significant intra-tumoral heterogeneity in PGE 2 content, 15-PGDH activity and NAD+ availability in human CRCLM. Tumour micro-environment (including hypoxia)-driven differences in PGE 2 metabolism should be targeted for novel treatment of advanced CRC

Induction of labor in patients with an unfavorable cervix after a cesarean using an osmotic dilator versus vaginal prostaglandin.

Science.gov (United States)

Maier, Josefine T; Metz, Melanie; Watermann, Nina; Li, Linna; Schalinski, Elisabeth; Gauger, Ulrich; Rath, Werner; Hellmeyer, Lars

2018-04-25

Trial of labor after cesarean (TOLAC) is a viable option for safe delivery. In some cases cervical ripening and subsequent labor induction is necessary. However, the commonly used prostaglandins are not licensed in this subgroup of patients and are associated with an increased risk of uterine rupture. This cohort study compares maternal and neonatal outcomes of TOLAC in women (n=82) requiring cervical ripening agents (osmotic dilator vs. prostaglandins). The initial Bishop scores (BSs) were 2 (0-5) and 3 (0-5) (osmotic dilator and prostaglandin group, respectively). In this retrospective analysis, Fisher's exact test, the Kruskal-Wallis rank sum test and Pearson's chi-squared test were utilized. Vaginal birth rate (including operative delivery) was 55% (18/33) in the osmotic dilator group vs. 51% (25/49) in the dinoprostone group (P 0.886). Between 97% and 92% (32/33 and 45/49) (100%, 100%) of neonates had an Apgar score of >8 after 1 min (5, 10 min, respectively). The time between administration of the agent and onset of labor was 36 and 17.1 h (mean, Dilapan-S® group, dinoprostone group, respectively). Time from onset of labor to delivery was similar in both groups with 4.4 and 4.9 h (mean, Dilapan-S® group, dinoprostone group, respectively). Patients receiving cervical ripening with Dilapan-S® required oxytocin in 97% (32/33) of cases. Some patients presented with spontaneous onset of labor, mostly in the dinoprostone group (24/49, 49%). Amniotomy was performed in 64% and 49% (21/33 and 24/49) of cases (Dilapan-S® group and dinoprostone group, respectively). This pilot study examines the application of an osmotic dilator for cervical ripening to promote vaginal delivery in women who previously delivered via cesarean section. In our experience, the osmotic dilator gives obstetricians a chance to perform induction of labor in these women.

Lung Myofibroblasts Are Characterized by Down-Regulated Cyclooxygenase-2 and Its Main Metabolite, Prostaglandin E2

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Gabasa, Marta; Royo, Dolores; Molina-Molina, Maria; Roca-Ferrer, Jordi; Pujols, Laura; Picado, Cesar

2013-01-01

Background Prostaglandin E2 (PGE2), the main metabolite of cyclooxygenase (COX), is a well-known anti-fibrotic agent. Moreover, myofibroblasts expressing α-smooth muscle actin (α-SMA), fibroblast expansion and epithelial-mesenchymal transition (EMT) are critical to the pathogenesis of idiopathic pulmonary fibrosis (IPF). Our aim was to investigate the expression of COX-2 and PGE2 in human lung myofibroblasts and establish whether fibroblast-myofibroblast transition (FMT) and EMT are associated with COX-2 and PGE2 down-regulation. Methods Fibroblasts obtained from IPF patients (n = 6) and patients undergoing spontaneous pneumothorax (control, n = 6) and alveolar epithelial cell line A549 were incubated with TGF-β1 and FMT and EMT markers were evaluated. COX-2 and α-SMA expression, PGE2 secretion and cell proliferation were measured after IL-1β and PGE2 incubation. Results Myofibroblasts from both control and IPF fibroblast cultures stimulated with IL-1β showed no COX-2 expression. IPF fibroblasts showed increased myofibroblast population and reduced COX-2 expression in response to IL-1β. TGF-β1 increased the number of myofibroblasts in a time-dependent manner. In contrast, TGF-β1 induced slight COX-2 expression at 4 h (without increase in myofibroblasts) and 24 h, but not at 72 h. Both IPF and control cultures incubated with TGF-β1 for 72 h showed diminished COX-2 induction, PGE2 secretion and α-SMA expression after IL-1β addition. The latter decreased proliferation in fibroblasts but not in myofibroblasts. A549 cells incubated with TGF-β1 for 72 h showed down-regulated COX-2 expression and low basal PGE2 secretion in response to IL-1β. Immuno-histochemical analysis of IPF lung tissue showed no COX-2 immuno-reactivity in myofibroblast foci. Conclusions Myofibroblasts are associated with COX-2 down-regulation and reduced PGE2 production, which could be crucial in IPF development and progression. PMID:23755232

Electroproduction of the Delta(1232) Resonance at High Momentum Transfer

International Nuclear Information System (INIS)

Valera Frolov; Gary Adams; Abdellah Ahmidouch; Christopher Armstrong; Ketevi Assamagan; Steven Avery; Baker, O.; Peter Bosted; Volker Burkert; Roger Carlini; Davidson, R.M.; James Dunne; Eden, T.; Rolf Ent; David Gaskell; Paul Gueye; Wendy Hinton; Cynthia Keppel; Wooyoung Kim; Mike Klusman; Douglas Koltenuk; David Mack; Richard Madey; David Meekins; Ralph Minehart; Joseph Mitchell; Hamlet Mkrtchyan; Mukhopadhyay, N.C.A.; James Napolitano; Gabriel Niculescu; Maria-Ioana Niculescu; Mina Nozar; John Price; Paul Stoler; Vardan Tadevosyan; Liguang Tang; Michael Witkowski; Stephen Wood

1999-01-01

Jefferson Lab experiment E94-014 measured the excitation of the Delta (1232) resonance via the reaction p(e,e(prime)p)π 0 at Q 2 near 2.8 and 4 Gev 2 . This is the highest Q 2 for which exclusive resonance electroproduction has ever been observed. Decay distributions of the Delta (1232) resonance into the ppi 0 final state were measured over a wide range of barycentric decay angles and energies. The goal of this experiment is to assess the transition in Q 2 from the constituent quark model (CQM) to the regime where hard processes become important. At Q 2 ∼ few GeV 2 /c 2 the ratio E 1+ /M 1+ depends dramatically on the theoretical description, varying from a few 10 -2 in the CQM limit, to about 1 in the pQCD limit. Preliminary analysis of the data shows that the ratio E 1+ /M 1+ remains small at Q 2 up to 4 Gev 2 /c 2 . After first pass analysis we obtain E 1+ /M 1+ = -4.1 ± 1.2 at Q 2 = 2.8 Gev 2 /c 2 and E 1+ /M 1+ = -7.9 ± 0.8 at Q 2 = 4 Gev 2 /c 2 (statistical errors only)

Association of papillomavirus E6 proteins with either MAML1 or E6AP clusters E6 proteins by structure, function, and evolutionary relatedness.

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Nicole Brimer

2017-12-01

Full Text Available Papillomavirus E6 proteins bind to LXXLL peptide motifs displayed on targeted cellular proteins. Alpha genus HPV E6 proteins associate with the cellular ubiquitin ligase E6AP (UBE3A, by binding to an LXXLL peptide (ELTLQELLGEE displayed by E6AP, thereby stimulating E6AP ubiquitin ligase activity. Beta, Gamma, and Delta genera E6 proteins bind a similar LXXLL peptide (WMSDLDDLLGS on the cellular transcriptional co-activator MAML1 and thereby repress Notch signaling. We expressed 45 different animal and human E6 proteins from diverse papillomavirus genera to ascertain the overall preference of E6 proteins for E6AP or MAML1. E6 proteins from all HPV genera except Alpha preferentially interacted with MAML1 over E6AP. Among animal papillomaviruses, E6 proteins from certain ungulate (SsPV1 from pigs and cetacean (porpoises and dolphins hosts functionally resembled Alpha genus HPV by binding and targeting the degradation of E6AP. Beta genus HPV E6 proteins functionally clustered with Delta, Pi, Tau, Gamma, Chi, Mu, Lambda, Iota, Dyokappa, Rho, and Dyolambda E6 proteins to bind and repress MAML1. None of the tested E6 proteins physically and functionally interacted with both MAML1 and E6AP, indicating an evolutionary split. Further, interaction of an E6 protein was insufficient to activate degradation of E6AP, indicating that E6 proteins that target E6AP co-evolved to separately acquire both binding and triggering of ubiquitin ligase activation. E6 proteins with similar biological function clustered together in phylogenetic trees and shared structural features. This suggests that the divergence of E6 proteins from either MAML1 or E6AP binding preference is a major event in papillomavirus evolution.

Ionotropic glutamate receptors (iGluRs of the delta family (GluD1 and GluD2 and synaptogenesis

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Muhammad Zahid Khan

2017-08-01

Full Text Available Glutamate delta-1 (GluD1 and glutamate delta-2 (GluD2 form the delta family of ionotropic glutamate receptors (iGluRs and are distinct from other (iGluRs in that they do not exhibit typical agonist-induced ion channel currents. Recent studies have demonstrated a crucial role of the delta receptors in synapse formation by interacting with presynaptic proteins such as Neurexin1. This review presents current knowledge regarding the expression, structure and function of Glu delta receptors (GluD1, GluD2 in brain, focusing on synapse formation, function and dysfunction.

Quality of life of glaucoma patients under medical therapy with different prostaglandins

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Paletta Guedes RA

2012-10-01

Full Text Available Ricardo Augusto Paletta Guedes,1–3 Vanessa Maria Paletta Guedes,1–3, Sirley Maria Freitas,2 Alfredo Chaoubah11Federal University of Juiz de Fora, Juiz de Fora, Minas Gerais, Brazil; 2Paletta Guedes Ophthalmological Center, Juiz de Fora, MG, Brazil; 3Santa Casa de Misericórdia Hospital, Juiz de Fora, Minas Gerais, BrazilPurpose: To assess the quality of life of glaucoma patients under medical therapy with different prostaglandin analogs.Methods: A cross-sectional study of consecutive glaucoma patients was designed. We assessed the patients' quality of life through the Brazilian 25-question version of the National Eye Institute Visual Functioning Questionnaire, comprising 12 subscales (general health, general vision, ocular pain, near vision, distance vision, social function, mental health, role limitations, dependency, driving, color vision, and peripheral vision and a total composite score. Clinical features, including current medical treatment, were obtained from each patient's medical record. Three groups of patients were identified according to the prostaglandin in use: bimatoprost, latanoprost, or travoprost. The main outcome measures were: mean score in each subscale and mean total composite score.Results: The mean total composite score for the whole group was 70.60. The bimatoprost, latanoprost, and travoprost groups had the following mean composite scores, respectively: 56.56, 77.36, and 71.08 (P = 0.001, analysis of variance [ANOVA]. Latanoprost and travoprost results were similar, and both were superior to bimatoprost. Most subscales had similar results. The subscale with the lowest score for all groups was general health. Groups were homogenous and comparable.Conclusion: There is a difference in the quality of life between glaucoma patients using prostaglandin analogs. It seems that bimatoprost users have lower QoL when compared to latanoprost and travoprost users.Keywords: glaucoma, medical treatment, prostaglandin analogs

Presence of crevicular fluid Prostaglandin E2 in relation with clinical and radiographic periodontal status

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Javier Elpidio Monzón

2016-07-01

Full Text Available Background and Objectives: Prostaglandin E2 (PGE2 is present in gingival crevicular fluid the (GCF and is evidenced in periodontal disease (PD. However, there are no enough reports to correlate the PGE2 concentrations in GCF in periodontal health and disease with clinical and radiographic indicators, age and gender. Hence, the present study is aimed to estimate the levels of PGE2 in GCF of subjects without periodontal disease (SEP and periodontal disease (CEP. Materials and Methods: 99 subjects were selected, 33 without PD (G1 and 66 with PD, 33 with gingivitis (G2 and 33 with periodontitis (G3, which were submitted to a clinical and radiographic diagnosis, registering samples FGC, being stored, centrifuged and refrigerated for preservation. Subsequently the concentration of crevicular PGE2 was measured by using the enzyme linked immunosorbent assay (ELISA, determining the concentration of each subject. Results: PGE2 was detected in all the samples. The G1 presented a concentration of 28.82 ± 2.88 pg / mL, G2 44.91 ± 4.37 pg / mL and G3 148.67 ± 74.74 pg / mL (0.0001. PGE2 levels were significantly correlated with bleeding on probing, probing depth, attachment loss and bone loss (0.05. PGE2 levels were modified by age, but not gender. Conclusion: It is well known that activated inflammatory cells produce inflammatory mediators that stimulate the production of PGE2. The findings of this study demonstrate an increased concentration of PGE2 in FCG according to the presence of greater severity of PD. PGE2 may be considered as a biomarker in PD progression. However, controlled, longitudinal studies are needed to confirm this possibility.

Water vapor δ17O measurements using an off-axis integrated cavity output spectrometer and seasonal variation in 17O-excess of precipitation in the east-central United States

Science.gov (United States)

Tian, C.; Wang, L.; Novick, K. A.

2016-12-01

High-precision triple oxygen isotope analysis can be used to improve our understanding of multiple hydrological and meteorological processes. Recent studies focus on understanding 17O-excess variation of tropical storms, high-latitude snow and ice-core as well as spatial distribution of meteoric water (tap water). The temporal scale of 17O-excess variation in middle-latitude precipitation is needed to better understand which processes control on the 17O-excess variations. This study focused on assessing how the accuracy and precision of vapor δ17O laser spectroscopy measurements depend on vapor concentration, delta range, and averaging-time. Meanwhile, we presented 17O-excess data from two-year, event based precipitation sampling in the east-central United States. A Triple Water Vapor Isotope Analyzer (T-WVIA) was used to evaluate the accuracy and precision of δ2H, δ18O and δ17O measurements. GISP and SLAP2 from IAEA and four working standards were used to evaluate the sensitivity in the three factors. Overall, the accuracy and precision of all isotope measurements were sensitive to concentration, with higher accuracy and precision generally observed under moderate vapor concentrations (i.e., 10000-15000 ppm) for all isotopes. Precision was also sensitive to the range of delta values, though the effect was not as large when compared to the sensitivity to concentration. The precision was much less sensitive to averaging time when compared with concentration and delta range effects. The preliminary results showed that 17O-excess variation was lower in summer (23±17 per meg) than in winter (34±16 per meg), whereas spring values (30±21 per meg) was similar to fall (29±13 per meg). That means kinetic fractionation influences the isotopic composition and 17O-excess in different seasons.

Microwave plasma generation and filtered transport of O{sub 2} (a {sup 1}{delta}{sub g})

Energy Technology Data Exchange (ETDEWEB)

Williams, Skip [Air Force Research Laboratory, Mail Stop PRAS, 1950 Fifth Street, WPAFB, OH 45433-7251 (United States); Popovic, Svetozar [Department of Physics, Old Dominion University, Norfolk, VA 23529 (United States); Gupta, Manish [Los Gatos Research, Incorporated 67 East Evelyn Ave, Suite 3, Mountain View, CA 94041 (United States)], E-mail: skip.williams@wpafb.af.mil

2009-08-01

Singlet oxygen, O{sub 2}(a {sup 1}{delta}{sub g}), is generated using a low pressure, low power continuous microwave discharge operating at 2.45 GHz with a flow of helium seeded with 1-10% molecular oxygen. The absolute concentration of O{sub 2}(a {sup 1}{delta}{sub g}) is measured using off-axis integrated cavity output spectroscopy to probe the Q-branch transition of the (1, 0) band of the b{sup 1}{sigma}{sub g}{sup +}-a{sup 1}{delta}{sub g} Noxon system. In order to remove other energetic species from the flow, the post-discharge flow is passed through a coarse fritted quartz filter. The use of the quartz frit takes advantage of the substantially lower surface sticking probability of O{sub 2}(a {sup 1}{delta}{sub g}) in comparison with other excited species on the flow. Up to 6% of the total oxygen passing through the filter remains in the a {sup 1}{delta}{sub g} state, and absolute densities of 2.5 x 10{sup 14} cm{sup -3} are obtained using this method. This preparation method and transport is important in developing sources of singlet oxygen for kinetic and spectroscopic studies.

Chloroquine, quinine, procaine, quinidine, tricyclic antidepressants, and methylxanthines as prostaglandin agonists and antagonists.

Science.gov (United States)

Manku, M S; Horrobin, D F

1976-11-20

Chloroquine, quanine, procaine, quinidine, clomipramine, theophylline, and caffeine have been shown to be strong prostaglandin antagonists and weak agonists. The antagonist effect is clearly demonstrable at concentrations reached in human plasma when the drugs are used therapeutically. This suggests that prostaglandins are important in several situations in which their role has hitherto been unsuspected. New approaches to the development of prostaglandin antagonists and new uses for established drugs are indicated. In a preliminary study chloroquine has been successfully used to close patent ductus arteriosus in three infants.

Abraham Reef Stable Isotope Data (delta 13C, delta 18O, delta 14C) for 1635-1957

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Site: Abraham Reef, 22ó 06'S, 153ó 00'E, Porites australiensus, Radiocarbon (delta 14C) and Stable Isotope (del 18O and del 13C) results from bi-annual samples from...

Induction of neutrophil gelatinase-associated lipocalin expression by co-stimulation with interleukin-17 and tumor necrosis factor-alpha is controlled by IkappaB-zeta but neither by C/EBP-beta nor C/EBP-delta

DEFF Research Database (Denmark)

Karlsen, Joachim R; Borregaard, Niels; Cowland, Jack B

2010-01-01

-alpha in the presence of IL-17, a pro-inflammatory cytokine produced by the newly discovered subset of CD4(+) T helper cells, T(H)-17. In contrast to the murine NGAL orthologue, 24p3/lipocalin 2, we found no requirement for C/EBP-beta or C/EBP-delta for NGAL induction by IL-17 and TNF-alpha as neither small interfering...

Prostaglandin E synthase interacts with inducible heat shock protein 70 after heat stress in bovine primary dermal fibroblast cells.

Science.gov (United States)

Richter, Constanze; Viergutz, Torsten; Schwerin, Manfred; Weitzel, Joachim M

2015-01-01

Exposure to heat stress in dairy cows leads to undesired side effects that are reflected by complex alterations in endocrine parameters, such as reduced progesterone, estradiol, and thyroid hormone concentrations. These endocrine maladaptation leads to failure to resume cyclicity, a poor uterine environment and inappropriate immune responses in postpartum dairy cows. Prostaglandins (PG's) are lipid mediators, which serve as signal molecules in response to various external stimuli as well as to cell-specific internal signal molecules. A central role in PG synthesis plays prostaglandin E synthase (PGES) that catalyzes the isomerization of PGH2 to PGE2 .The present study was conducted to investigate heat stress associated PGES expression. Expression of PGES and inducible heat shock protein 70 (HSP70), as a putative chaperonic protein, was studied in bovine primary fibroblasts under different heat shock conditions. Bovine primary fibroblasts produce PGE2 at homoiothermical norm temperature (38.5°C in bovine), but reduce PGE2 production rates under extreme heat stress (at 45°C for 6 h). By contrast, PGE2 production rates are maintained after a milder heat stress (at 41.5°C for 6 h). PGE2 synthesis is abolished by application of cyclooxygenase inhibitor indomethacin, indicating de novo synthesis. Heat stress increases HSP70 but not PGES protein concentrations. HSP70 physically interacts with PGES and the PGES-HSP70 complex did not dissociate upon heat stress at 45°C even after returning the cells to 37°C. The PGE2 production negatively correlates with the portion of PGES-HSP70 complex. These results suggest a protein interaction between HSP70 and PGES in dermal fibroblast cells. Blockage of PGES protein by HSP70 seems to interfere with the regulatory processes essential for cellular adaptive protection. © 2014 International Society for Advancement of Cytometry. © 2014 International Society for Advancement of Cytometry.

Neuroinflammation and J2 prostaglandins: linking impairment of the ubiquitin-proteasome pathway and mitochondria to neurodegeneration

Directory of Open Access Journals (Sweden)

Maria Emilia Figueiredo-Pereira

2015-01-01

Full Text Available The immune response of the CNS is a defense mechanism activated upon injury to initiate repair mechanisms while chronic over-activation of the CNS immune system (termed neuroinflammation may exacerbate injury. The latter is implicated in a variety of neurological and neurodegenerative disorders such as Alzheimer and Parkinson diseases, amyotrophic lateral sclerosis, multiple sclerosis, traumatic brain injury, HIV dementia and prion diseases. Cyclooxygenases (COX -1 and COX-2, which are key enzymes in the conversion of arachidonic acid into bioactive prostanoids, play a central role in the inflammatory cascade. J2 prostaglandins are endogenous toxic products of cyclooxygenases, and because their levels are significantly increased upon brain injury, they are actively involved in neuronal dysfunction induced by pro-inflammatory stimuli. In this review, we highlight the mechanisms by which J2 prostaglandins (1 exert their actions, (2 potentially contribute to the transition from acute to chronic inflammation and to the spreading of neuropathology, (3 disturb the ubiquitin-proteasome pathway and mitochondrial function, and (4 contribute to neurodegenerative disorders such as Alzheimer and Parkinson diseases, and amyotrophic lateral sclerosis, as well as stroke, traumatic brain injury, and demyelination in Krabbe disease. We conclude by discussing the therapeutic potential of targeting the J2 prostaglandin pathway to prevent/delay neurodegeneration associated with neuroinflammation. In this context, we suggest a shift from the traditional view that cyclooxygenases are the most appropriate targets to treat neuroinflammation, to the notion that J2 prostaglandin pathways and other neurotoxic prostaglandins downstream from cyclooxygenases, would offer significant benefits as more effective therapeutic targets to treat chronic neurodegenerative diseases, while minimizing adverse side effects.

Prostaglandin E2 released from activated microglia enhances astrocyte proliferation in vitro

International Nuclear Information System (INIS)

Zhang Dan; Hu Xiaoming; Qian Li; Wilson, Belinda; Lee, Christopher; Flood, Patrick; Langenbach, Robert; Hong, J.-S.

2009-01-01

Microglial activation has been implicated in many astrogliosis-related pathological conditions including astroglioma; however, the detailed mechanism is not clear. In this study, we used primary enriched microglia and astrocyte cultures to determine the role of microglial prostaglandin E 2 (PGE 2 ) in the proliferation of astrocytes. The proliferation of astrocytes was measured by BrdU incorporation. The level of PGE 2 was measured by ELISA method. Pharmacological inhibition or genetic ablation of COX-2 in microglia were also applied in this study. We found that proliferation of astrocytes increased following lipopolysaccharide (LPS) treatment in the presence of microglia. Furthermore, increased proliferation of astrocytes was observed in the presence of conditioned media from LPS-treated microglia. The potential involvement of microglial PGE 2 in enhanced astrocyte proliferation was suggested by the findings that PGE 2 production and COX-2 expression in microglia were increased by LPS treatment. In addition, activated microglia-induced increases in astrocyte proliferation were blocked by the PGE 2 antagonist AH6809, COX-2 selective inhibitor DuP-697 or by genetic knockout of microglial COX-2. These findings were further supported by the finding that addition of PGE 2 to the media significantly induced astrocyte proliferation. These results indicate that microglial PGE 2 plays an important role in astrocyte proliferation, identifying PGE 2 as a key neuroinflammatory molecule that triggers the pathological response related to uncontrollable astrocyte proliferation. These findings are important in elucidating the role of activated microglia and PGE 2 in astrocyte proliferation and in suggesting a potential avenue in the use of anti-inflammatory agents for the therapy of astroglioma.

Role of adrenal hormones and prostaglandins in the control of mouse thymocytes lysis.

Science.gov (United States)

Durant, S; Seillan, C; Duval, D; Homo-Delarche, F

1984-01-01

The cytolytic actions of glucocorticoids and of agents increasing cyclic AMP were studied in vitro in thymocyte suspensions isolated from adrenalectomized or hydrocortisone-treated mice. Although considered as corticoresistant cells, the thymocytes isolated from hydrocortisone-treated mice were lysed to the same extent although more slowly in vitro by dexamethasone than whole thymocyte populations (i.e. corticosensitive cells). Moreover, these two cell populations were shown to contain comparable amounts of glucocorticoid receptors and to be almost equally sensitive to the metabolic effects of glucocorticoids when measured by inhibition of RNA and DNA synthesis. Studies performed with corticosensitive cells showed that prostaglandin E2, isoproterenol and dibutyrilcyclic AMP were also able to induce cell lysis and that, isoproterenol and dexamethasone exerted additive cytolytic action in vitro. In vivo experiments showed also an additive effect of steroids and isoproterenol on thymus atrophy. In contrast, cells isolated from hydrocortisone-treated animals were not sensitive to the cytotoxic action of prostaglandin E2, isoproterenol and dibutyril cyclic AMP. This difference between the two populations was not associated with any difference in the responsiveness of adenylate cyclase as determined following isoproterenol-induced accumulation of cyclic AMP. The cytolytic action of dexamethasone but also that of prostaglandin E2 and isoproterenol, could be blocked in the presence of cycloheximide, an inhibitor of protein synthesis, thus suggesting that glucocorticoids and agents increasing cyclic AMP control the synthesis of some proteins involved in the triggering of cell lysis. Among the hypotheses proposed to explain the differences between in vitro and in vivo sensitivity of lymphoid cell to glucocorticoids, it was suggested that the drug may in vivo indirectly control the viability or the proliferation of thymocytes through the release of other mediators. We have

Effects of a single administration of prostaglandin F2alpha, or a combination of prostaglandin F2alpha and prostaglandin E2, or placebo on fertility variables in dairy cows 3-5 weeks post partum, a randomized, double-blind clinical trial.

Science.gov (United States)

Hirsbrunner, Gaby; Burkhardt, Heinz W; Steiner, Adrian

2006-12-21

Delayed uterine involution has negative effects on the fertility of cows; use of prostaglandin F2alpha alone as a single treatment has not been shown to consistently improve fertility. Combined administration of PGF2alpha and PGE2 increased uterine pressure in healthy cows. We hypothesized, that the combination of both prostaglandins would accelerate uterine involution and have, therefore, a positive effect on fertility variables. In commercial dairy farming, the benefit of a single post partum combined prostaglandin treatment should be demonstrated. 383 cows from commercial dairy farms were included in this study. Uterine size and secretion were evaluated at treatment 21-35 days post partum and 14 days later. Cows were randomly allocated to one of three treatment groups: PGF2alpha and PGE2, PGF2alpha or placebo. For every animal participating in the study, the following reproduction variables were recorded: Interval from calving to first insemination, days open, number of artificial inseminations (AI) to conception; subsequent treatment of uterus, subsequent treatment of ovaries. Plasma progesterone level at time of treatment was used as a covariable. For continuous measurements, analysis of variance was performed. Fisher's exact test for categorical non-ordered data and exact Kruskal-Wallis test for ordered data were used; pairwise group comparisons with Bonferroni adjustment of significance level were performed. There was no significant difference among treatment groups in uterine size. Furthermore, there was no significant difference among treatments concerning days open, number of AI, and subsequent treatment of uterus and ovaries. Days from calving to first insemination tended to be shorter for cows with low progesterone level given PGF2alpha and PGE2 in combination than for the placebo-group (P = 0.024). The results of this study indicate that the administration of PGF2alpha or a combination of PGF2alpha and PGE2 21 to 35 days post partum had no beneficial

Assessing Niger-Delta Wetland Resources: A Case-Study of Mangrove Ecosystem

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Anwan, R. H.; Ndimele, P. E.; Whenu, O. O.; Anetekhai, M. A.; Essien-Ibok, M. A.; Erondu, E. S.

2016-02-01

The Niger Delta is located in the Atlantic coast of Southern Nigeria and is the world's second largest delta with a coastline of about 450km. The Niger Delta region occupies a surface area of about 112,110km2, representing about 12% of Nigeria's total surface area. The Delta's environment can be broken down into four ecological zones: coastal barrier islands, mangrove swamp forests, freshwater swamps, and lowland rainforests. The mangrove swamps of Niger Delta, which is the largest delta in Africa constitute the dominant wetland ecosystem in the Niger Delta region and covers an area of about 1,900km2. Mangroves constitute important nurseries for fishes, crustaceans, sponges, algae and other invertebrates, and also acts as a sink, retaining pollutants from contaminated tidal water. The Niger Delta mangrove together with the creeks and rivers are a major source of food and livelihood for about 30 million people, which represents more than 17% of Nigeria's population. Other ecosystem services provided by this unique environment are flood control, ground water re-fill, reservoir of biodiversity, fuel wood, cultural values etc. This ecosystem also plays important role in climate change mitigation because of its high blue carbon sequestration potential. This is particularly important because of continuous gas flaring in Niger Delta from petroleum operations, which releases carbon dioxide among other gases into the atmosphere. This wetland is potentially a good site for ecotourism and also qualifies to be a world heritage site and Ramsar site if proper steps are taken. The benefits derivable from this fragile ecosystem are under severe threat by anthropogenic stressors. These include the installation of pipelines and seismic exploration by oil companies, crude oil pollution, deforestation, urbanization etc. This paper discusses the extent of depletion and loss of mangrove ecosystem in the Niger Delta region and the value of its goods and services.

Desenvolvimento da ferrita delta na solda e ZTA resultante de soldagem plasma pulsada em um aço inoxidável supermartensítico Delta-ferrite development in weld and HAZ produced by pulsed plasma arc welding in a supermartensitic stainless steel

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Sérgio L. Henke

2013-03-01

Full Text Available A ferrita delta é considerada uma fase indesejável na microestrutura dos aços inoxidáveis martensíticos haja vista a mesma poder influenciar no desempenho da resistência à fadiga, tenacidade e corrosão sob-tensão. Sendo assim, o objetivo deste trabalho foi investigar o efeito da soldagem plasma pulsada sobre a distribuição e quantidade de ferrita delta em um aço inoxidável supermartensítico. Para tal foram obtidos cordões por meio de fusão superficial sobre uma amostra de aço inoxidável supermartensítico de alta liga utilizando corrente pulsada e convencional. Em seguida foi efetuada a caracterização microestrutural, em especial da ferrita delta, via análises metalográficas por meio de microscopia óptica e eletrônica de varredura . Os experimentos revelaram que, para o mesmo aporte térmico, a pulsação de corrente promoveu a formação de ferrita delta na forma de bandas ao longo do cordão de solda e redução significativa desta fase na ZTA quando comparada à soldagem convencional.The objective of this study was to investigate the effect of pulsed plasma welding on the distribution and amount of delta ferrite which is considered an undesirable phase in a supermartensitic stainless steel. For such weld beads have been obtained by melting the surface of a sample of a high-alloy supermartensitic stainless steel using pulsed and conventional current. Microstructural characterization, especially of delta ferrite, was performed by metallographic analysis by means of optical microscopy and scanning electron microscopy. The experiments showed that for the same heat input, pulsed current promoted the formation of delta ferrite in the form of bands along the weld bead and caused a significant reduction of this phase in HAZ as compared to conventional welding.

Direct analysis of prostaglandin-E2 and -D2 produced in an inflammatory cell reaction and its application for activity screening and potency evaluation using turbulent flow chromatography liquid chromatography-high resolution mass spectrometry.

Science.gov (United States)

Shin, Jeong-Sook; Peng, Lei; Kang, Kyungsu; Choi, Yongsoo

2016-09-09

Direct analysis of prostaglandin-E2 (PGE2) and -D2 (PGD2) produced from a RAW264.7 cell-based reaction was performed by liquid chromatography high-resolution mass spectrometry (LC-HRMS), which was online coupled with turbulent flow chromatography (TFC). The capability of this method to accurately measure PG levels in cell reaction medium containing cytokines or proteins as a reaction byproduct was cross-validated by two conventional methods. Two methods, including an LC-HRMS method after liquid-liquid extraction (LLE) of the sample and a commercial PGE2 enzyme-linked immunosorbent assay (ELISA), showed PGE2 and/or PGD2 levels almost similar to those obtained by TFC LC-HRMS over the reaction time after LPS stimulation. After the cross-validation, significant analytical throughputs, allowing simultaneous screening and potency evaluation of 80 natural products including 60 phytochemicals and 20 natural product extracts for the inhibition of the PGD2 produced in the cell-based inflammatory reaction, were achieved using the TFC LC-HRMS method developed. Among the 60 phytochemicals screened, licochalcone A and formononetin inhibited PGD2 production the most with IC50 values of 126 and 151nM, respectively. For a reference activity, indomethacin and diclofenac were used, measuring IC50 values of 0.64 and 0.21nM, respectively. This method also found a butanol extract of Akebia quinata Decne (AQ) stem as a promising natural product for PGD2 inhibition. Direct and accurate analysis of PGs in the inflammatory cell reaction using the TFC LC-HRMS method developed enables the high-throughput screening and potency evaluation of as many as 320 samples in less than 48h without changing a TFC column. Copyright © 2016 Elsevier B.V. All rights reserved.

Sequence analysis of 17 NRXN1 deletions

DEFF Research Database (Denmark)

Hoeffding, Louise Kristine Enggaard; Hansen, Thomas; Ingason, Andrés

2014-01-01

into the molecular mechanisms governing such genomic rearrangements may increase our understanding of disease pathology and evolutionary processes. Here we analyse 17 carriers of non-recurrent deletions in the NRXN1 gene, which have been associated with neurodevelopmental disorders, e.g. schizophrenia, autism...

Prostaglandin E2/leukotriene B4 balance induced by Lutzomyia longipalpis saliva favors Leishmania infantum infection.

Science.gov (United States)

Araújo-Santos, Théo; Prates, Deboraci Brito; França-Costa, Jaqueline; Luz, Nívea F; Andrade, Bruno B; Miranda, José Carlos; Brodskyn, Claudia I; Barral, Aldina; Bozza, Patrícia T; Borges, Valéria Matos

2014-12-20

Eicosanoids and sand fly saliva have a critical role in the Leishmania infection. Here, we evaluated the effect of Lutzomyia longipalpis salivary gland sonicate (SGS) on neutrophil and monocyte recruitment and activation of eicosanoid production in a murine model of inflammation. C57BL/6 mice were inoculated intraperitonealy with Lutzomyia longipalpis SGS or Leishmania infantum or both, followed by analyses of cell recruitment, parasite load and eicosanoid production. Intraperitoneal injection of Lutzomyia longipalpis SGS together with Leishmania infantum induced an early increased parasite viability in monocytes and neutrophils. L. longipalpis SGS increased prostaglandin E2 (PGE2), but reduced leukotriene B4 (LTB4) production ex vivo in peritoneal leukocytes. In addition, the pharmacological inhibition of cyclooxygenase 2 (COX-2) with NS-398 decreased parasite viability inside macrophages during Leishmania infection in the presence of L. longipalpis SGS arguing that PGE2 production is associated with diminished parasite killing. These findings indicate that L. longipalpis SGS is a critical factor driving immune evasion of Leishmania through modulation of PGE2/LTB4 axis, which may represent an important mechanism on establishment of the infection.

Deltas on the move. Making deltas cope with the effects of climate change

International Nuclear Information System (INIS)

Reker, J.; Van Winden, A.; Braakhekke, W.; Vermaat, J.; Eleveld, M.; Janssen, R.; De Reus, N.; Omzigt, N.

2006-01-01

This scoping study is the first phase of a study aimed at: (a) providing knowledge on the potential of a system-based approach to deal with the effects of climate change as an alternative for the more traditional technical measures such as dams, dikes and surge barriers. This should be shown for both rich and poor countries and should address hydrological, ecological as well as socio-economic aspects; and (b) identifying the potential to market these results worldwide. To reach these objectives four research steps are defined: (1) to make an inventory of deltas: their vulnerability to the effects of climate change; (2) development of indicators for successful use of a system-based approach; (3) to provide an overview of the potential of soft measures for these deltas; (4) to select a number of deltas with potential for marketing system-based measures and the development of strategies to link economic and ecological objectives. This scoping study addresses step 1 only. The results from step 1 will be used as a starting point for steps 2 and 3. The outputs of this scoping study are threefold: a background report (this report); a flyer with a brief description of the findings; a website with information on delta's and how these may be affected by climate change. The scoping study will roughly outline which deltas are still functioning in a more or less natural manner - or could be (re)developed in that direction - and thus would be good candidates for a system-based approach. Chapter 2 gives a description of the geomorphological and ecological processes in a delta. In addition, those aspects of climate change that can have an effect on deltas are described. The third chapter deals with human interventions in deltas and whether or not they fit within a system-based approach. In a system-based approach, as presented in Chapter 4, natural processes are given free reign where possible. Chapter 5 shows how available data on deltas could be used in such a system

SME observations of O2(1 Delta g) nightglow - An assessment of the chemical production mechanisms

Science.gov (United States)

Howell, Colin D.; Michelangeli, Diane V.; Allen, Mark; Yung, Yuk L.; Thomas, Ronald J.

1990-01-01

Solar Mesosphere Explorer (SME) observations of the 3 a.m. 1.27 micron nightglow at 45 N latitude are reported. From the deduced volume emission rates, the O2(a 1 Delta g) nighttime production rates for the 80-100 km altitude range are derived. Utilizing the mean SME-acquired 3 p.m. ozone profile for the same latitude and time period and an updated photochemical model, nighttime O, O3, H, OH, HO2, and H2O2 profiles are determined. These are used in calculating the rates of reactions which are sufficiently exothermic to produce O2(1 Delta) or excited states of OH or HO2, which could transfer their energy to O2 to form O2(1 Delta). Yields of O2(1 Delta) based on published laboratory and observational studies are used to find that the sum of two reaction sequences can approximate the SME measurements: (1) O + O + M and (2) H + O3 followed by OH-asterisk + O2.

Is there a self-organization principle of river deltas?

Science.gov (United States)

Tejedor, Alejandro; Longjas, Anthony; Foufoula-Georgiou, Efi

2017-04-01

River deltas are known to possess a complex topological and flux-partitioning structure which has recently been quantified using spectral graph theory [Tejedor et al., 2015a,b]. By analysis of real and simulated deltas it has also been shown that there is promise in formalizing relationships between this topo-dynamic delta structure and the underlying delta forming processes [e.g., Tejedor et al., 2016]. The question we pose here is whether there exists a first order organizational principle behind the self-organization of river deltas and whether this principle can be unraveled from the co-evolving topo-dynamic structure encoded in the delta planform. To answer this question, we introduce a new metric, the nonlocal Entropy Rate (nER) that captures the information content of a delta network in terms of the degree of uncertainty in delivering fluxes from any point of the network to the shoreline. We hypothesize that if the "guiding principle" of undisturbed deltas is to efficiently and robustly build land by increasing the diversity of their flux pathways over the delta plane, then they would exhibit maximum nonlocal Entropy Rate at states at which geometry and flux dynamics are at equilibrium. At the same time, their nER would be non-optimal at transient states, such as before and after major avulsions during which topology and dynamics adjust to each other to reach a new equilibrium state. We will present our results for field and simulated deltas, which confirm this hypothesis and open up new ways of thinking about self-organization, complexity and robustness in river deltas. One particular connection of interest might have important implications since entropy rate and resilience are related by the fluctuation theorem [Demetrius and Manke, 2005], and therefore our results suggest that deltas might in fact self-organize to maximize their resilience to structural and dynamic perturbations. References: Tejedor, A., A. Longjas, I. Zaliapin, and E. Foufoula

NO2 inhalation promotes Alzheimer’s disease-like progression: cyclooxygenase-2-derived prostaglandin E2 modulation and monoacylglycerol lipase inhibition-targeted medication

Science.gov (United States)

Yan, Wei; Yun, Yang; Ku, Tingting; Li, Guangke; Sang, Nan

2016-03-01

Air pollution has been reported to be associated with increased risks of cognitive impairment and neurodegenerative diseases. Because NO2 is a typical primary air pollutant and an important contributor to secondary aerosols, NO2-induced neuronal functional abnormalities have attracted greater attention, but the available experimental evidence, modulating mechanisms, and targeting medications remain ambiguous. In this study, we exposed C57BL/6J and APP/PS1 mice to dynamic NO2 inhalation and found for the first time that NO2 inhalation caused deterioration of spatial learning and memory, aggravated amyloid β42 (Aβ42) accumulation, and promoted pathological abnormalities and cognitive defects related to Alzheimer’s disease (AD). The microarray and bioinformation data showed that the cyclooxygenase-2 (COX-2)-mediated arachidonic acid (AA) metabolism of prostaglandin E2 (PGE2) played a key role in modulating this aggravation. Furthermore, increasing endocannabinoid 2-arachidonoylglycerol (2-AG) by inhibiting monoacylglycerol lipase (MAGL) prevented PGE2 production, neuroinflammation-associated Aβ42 accumulation, and neurodegeneration, indicating a therapeutic target for relieving cognitive impairment caused by NO2 exposure.

CCL20, (gamma)(delta) T cells, and IL-22 in corneal epithelial healing

Science.gov (United States)

After corneal epithelial abrasion, leukocytes and platelets rapidly enter the corneal stroma, and CCR6 (+) IL-17(+) gamma delta T cells migrate into the epithelium. Gamma delta T-cell-deficient (TCRd(-/-)) mice have significantly reduced inflammation and epithelial wound healing. Epithelial CCL20 mR...

Evaluation Of Delta State E-Government Website | Chete ...

African Journals Online (AJOL)

The study evaluates Delta state government website by adopting the method used since 2001 in evaluating national government websites. The questionnaire and web survey techniques were adopted for this study. The data from the questionnaire was analyzed using statistical package for social sciences (SPSS) and the ...

Geology of the UE17e drill hole, Area 17, Nevada Test Site

International Nuclear Information System (INIS)

Hodson, J.N.; Hoover, D.L.

1979-03-01

The UE17e drill hole, located at the northwest corner of Syncline Ridge, was cored from 3.05 m (10 ft) to a total depth of 914.4 m (3,000 ft) in unit J (Mississippian) of the Eleana (Devonian and Mississippian) to obtain samples for mineral, chemical, and physical-property analyses. UE17e penetrated 73.5 m (241 ft) of the quartzite subunit and 840.9 m (2,759 ft) of the argillite subunit of unit J. Less than 0.4 percent quartzite is present in the argillite subunit. Dips range from 12 0 to 18 0 . Twenty-three faults were observed in the core or on geophysical logs. Most of these faults affect only a few meters of the core and probably have displacements of a few meters. The majority of fractures are parallel to bedding planes. Fracture frequency ranges from 3.4 to 9.4 fractures per meter in the upper part of the cored interval and 1.4 to 5.9 fractures per meter in the lower part of the cored interval. The core index indicates that the lower part of the hole is more competent than the upper part. Lower competency in the upper part of the hole may be caused by weathering and/or near-surface stress relief. Physical, mechanical, and thermal property measurements indicate that bedding and fracturing are the major factors in variation of properties between samples. 17 figures, 10 tables

Prostaglandin E2 is essential for efficacious skeletal muscle stem-cell function, augmenting regeneration and strength.

Science.gov (United States)

Ho, Andrew T V; Palla, Adelaida R; Blake, Matthew R; Yucel, Nora D; Wang, Yu Xin; Magnusson, Klas E G; Holbrook, Colin A; Kraft, Peggy E; Delp, Scott L; Blau, Helen M

2017-06-27

Skeletal muscles harbor quiescent muscle-specific stem cells (MuSCs) capable of tissue regeneration throughout life. Muscle injury precipitates a complex inflammatory response in which a multiplicity of cell types, cytokines, and growth factors participate. Here we show that Prostaglandin E2 (PGE2) is an inflammatory cytokine that directly targets MuSCs via the EP4 receptor, leading to MuSC expansion. An acute treatment with PGE2 suffices to robustly augment muscle regeneration by either endogenous or transplanted MuSCs. Loss of PGE2 signaling by specific genetic ablation of the EP4 receptor in MuSCs impairs regeneration, leading to decreased muscle force. Inhibition of PGE2 production through nonsteroidal anti-inflammatory drug (NSAID) administration just after injury similarly hinders regeneration and compromises muscle strength. Mechanistically, the PGE2 EP4 interaction causes MuSC expansion by triggering a cAMP/phosphoCREB pathway that activates the proliferation-inducing transcription factor, Nurr1 Our findings reveal that loss of PGE2 signaling to MuSCs during recovery from injury impedes muscle repair and strength. Through such gain- or loss-of-function experiments, we found that PGE2 signaling acts as a rheostat for muscle stem-cell function. Decreased PGE2 signaling due to NSAIDs or increased PGE2 due to exogenous delivery dictates MuSC function, which determines the outcome of regeneration. The markedly enhanced and accelerated repair of damaged muscles following intramuscular delivery of PGE2 suggests a previously unrecognized indication for this therapeutic agent.

Evaluation of prostaglandin D2 as a CSF leak marker: implications in safe epidural anesthesia

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Kondabolu S

2011-07-01

Full Text Available Sirish Kondabolu, Rishimani Adsumelli, Joy Schabel, Peter Glass, Srinivas PentyalaDepartment of Anesthesiology, School of Medicine, Stony Brook Medical Center, Stony Brook, New York, USABackground: It is accepted that there is a severe risk of dural puncture in epidural anesthesia. Of major concern to anesthesiologists is unintentional spinal block. Reliable identification of cerebrospinal fluid (CSF from the aspirate is crucial for safe epidural anesthesia. The aim of this study was to determine whether prostaglandin D2 could be clinically used as a marker for the detection of CSF traces.Methods: After obtaining Institutional Review Board approval and patient consent, CSF was obtained from patients undergoing spinal anesthesia, and blood, urine, and saliva were obtained from normal subjects and analyzed for prostaglandin D2 (PGD. CSF (n=5 samples were diluted with local anesthetic (bupivacaine, normal saline and blood in the ratios of 1:5 and 1:10. PGD levels in the CSF samples were analyzed with a PGD-Methoxime (MOX EIA Kit (Cayman Chemicals, MI. This assay is based on the conversion of PGD to a stable derivative, which is analyzed with antiserum specific for PGD-MOX. Results: Different concentrations of pure PGD-MOX conjugate were analyzed by EIA and a standard curve was derived. PGD levels in CSF and CSF with diluents were determined and the values were extrapolated onto the standard curve. Our results show a well-defined correlation for the presence of PGD both in straight CSF samples and in diluted CSF (dilution factor of 1:5 and 1:10. Conclusion: Prostaglandin D2 was reliably identified in CSF by enzyme-linked immunosorbent assay when diluted with local anesthetic, saline, and serum, and can be used as a marker to identify the presence of CSF in epidural aspirates.Keywords: epidural, cerebrospinal fluid, leak, marker, prostaglandin D2

Interleukin-6 as an endogenous pyrogen: induction of prostaglandin E2 in brain but not in peripheral blood mononuclear cells.

Science.gov (United States)

Dinarello, C A; Cannon, J G; Mancilla, J; Bishai, I; Lees, J; Coceani, F

1991-10-25

Fever induced by endogenous as well as exogenous pyrogens is often prevented by cyclooxygenase inhibitors; endogenous pyrogens stimulate prostaglandin E2 (PGE2) in or near the thermoregulatory centers of the brain. The cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF), are two pyrogens which stimulate brain PGE2 formation during fever and also increase PGE2 synthesis in human mononuclear cells in vitro. In the present study, we examined whether interleukin-6 (IL-6) stimulates PGE2 formation in a manner similar to IL-1 and TNF. Both glycosylated and non-glycosylated forms of recombinant human IL-6 were tested. Following intravenous injection into rabbits, the glycosylated IL-6 was more pyrogenic than the non-glycosylated form and there was no evidence of synergy in the production of fever when IL-6 and IL-1 were given simultaneously. IL-6 fever was blocked by prior administration of the cyclooxygenase inhibitor ibuprofen. IL-6 was also pyrogenic in the cat by either the systemic or the intraventricular route. However, in both species, IL-6 was less effective than IL-1 beta. When given intraventricularly to cats, IL-6 produced an increase in PGE2 levels of the cerebrospinal fluid in parallel with the rise in body temperature. In the latter respect, IL-6 imitated IL-1 beta; however, IL-6 from 0.15-15 micrograms/ml did not increase mononuclear cell PGE2 production in vitro whereas IL-1 beta induced 20-30-fold increases in PGE2 at 100 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

17 keV and 30 eV Dirac neutrinos and a techniphoton

International Nuclear Information System (INIS)

Holdom, B.

1985-01-01

We consider four flavors of left-handed Weyl neutrinos forming two Dirac masses, of order 17 keV and 30 eV. The symmetry Lsub(e)+Lsub(tau)-Lsub(μ)-Lsub(lambda) ensures this form of the mass matrix and consistency with experiments. We show how it arises in a technicolor context. The structure of the model can incorporate a techniphoton, an unbroken U(1) gauge symmetry of technifermions, and this makes a 17 keV neutrino cosmologically unstable. (orig.)

Prostaglandin E2 EP2 Receptor Deletion Attenuates Intracerebral Hemorrhage-Induced Brain Injury and Improves Functional Recovery

Directory of Open Access Journals (Sweden)

Jenna L. Leclerc

2015-04-01

Full Text Available Intracerebral hemorrhage (ICH is a devastating type of stroke characterized by bleeding into the brain parenchyma and secondary brain injury resulting from strong neuroinflammatory responses to blood components. Production of prostaglandin E2 (PGE2 is significantly upregulated following ICH and contributes to this inflammatory response in part through its E prostanoid receptor subtype 2 (EP2. Signaling through the EP2 receptor has been shown to affect outcomes of many acute and chronic neurological disorders; although, not yet explored in the context of ICH. Wildtype (WT and EP2 receptor knockout (EP2−/− mice were subjected to ICH, and various anatomical and functional outcomes were assessed by histology and neurobehavioral testing, respectively. When compared with age-matched WT controls, EP2−/− mice had 41.9 ± 4.7% smaller ICH-induced brain lesions and displayed significantly less ipsilateral hemispheric enlargement and incidence of intraventricular hemorrhage. Anatomical outcomes correlated with improved functional recovery as identified by neurological deficit scoring. Histological staining was performed to begin investigating the mechanisms involved in EP2-mediated neurotoxicity after ICH. EP2−/− mice exhibited 45.5 ± 5.8% and 41.4 ± 8.1% less blood and ferric iron accumulation, respectively. Furthermore, significantly less striatal and cortical microgliosis, striatal and cortical astrogliosis, blood–brain barrier breakdown, and peripheral neutrophil infiltration were seen in EP2−/− mice. This study is the first to suggest a deleterious role for the PGE2-EP2 signaling axis in modulating brain injury, inflammation, and functional recovery following ICH. Targeting the EP2 G protein-coupled receptor may represent a new therapeutic avenue for the treatment of hemorrhagic stroke.

Molecular cloning and characterization of the porcine prostaglandin transporter (SLCO2A1: evaluation of its role in F4 mediated neonatal diarrhoea

Directory of Open Access Journals (Sweden)

Cox Eric

2009-10-01

Full Text Available Abstract Background Because prostaglandins are involved in many (pathophysiological processes, SLCO2A1 was already characterized in several species in an attempt to unravel specific processes/deficiencies. Here, we describe the molecular cloning and characterization of the porcine ortholog in order to evaluate its possible involvement in F4 enterotoxigenic E. coli mediated neonatal diarrhoea, based on a positional candidate gene approach study. Results Porcine SLCO2A1 is organized in 14 exons, containing an open reading frame of 1935 bp, encoding a 12-transmembrane organic anion cell surface transporter of 644 aa. The -388 to -5 upstream region comprises a (CpG48 island containing a number of conserved promoter elements, including a TATA box. A potential alternative promoter region was found in the conserved -973 to -700 upstream region. No consensus polyadenylation signal was discovered in the 3' UTR. Repeat sequences were found in 15% of all the non coding sequences. As expected for a multifunctional protein, a wide tissue distribution was observed. mRNA expression was found in the adrenal gland, bladder, caecum, colon (centripetal coil/centrifugal coil, diaphragm, duodenum, gallbladder, heart, ileum, jejunum, kidney, liver, longissimus dorsi muscle, lung, lymph node, mesenterium, rectum, spleen, stomach, tongue and ureter, but not in the aorta, oesophagus and pancreas. The promoter region and the exons (including the splice sites of SLCO2A1 were resequenced in 5 F4ab/ac receptor positive and 5 F4ab/ac receptor negative pigs. Two silent and 2 missense (both S → L at position 360 and 633 mutations were found, but none was associated with the F4ab/ac receptor phenotype. In addition, no phenotype associated differential mRNA expression or alternative/abberant splicing/polyadenylation was found in the jejunum. Conclusion The molecular cloning and characterization of porcine SLCO2A1 not only contributes to the already existing knowledge about the

Effects of indomethacin on plasma homovanillic acid concentration in normal subjects: a study of prostaglandin-dopamine interactions.

Science.gov (United States)

Kahn, R S; Davidson, M; Kanof, P; McQueeney, R T; Singh, R R; Davis, K L

1991-01-01

In laboratory animals, prostaglandins have been shown to act as endogenous neuromodulators of central dopamine (DA) activity. To examine the interaction between prostaglandins and DA in man, the effect of a prostaglandin synthesis inhibitor, indomethacin, was studied on plasma concentrations of the DA metabolite, homovanillic acid (pHVA). Indomethacin (150 mg PO) as compared to placebo significantly elevated mean pHVA concentrations in eight normal subjects. Results of this study support the hypothesis that, as in animals, inhibition of prostaglandin synthesis increases central DA turnover in man.

CRPS: A contingent hypothesis with prostaglandins as crucial conversion factor.

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van der Veen, Phe

2015-11-01

CRPS is an acute pain disease expressed as chronic pain with a severe loss of tissue and function. CRPS usually occurs after minor injuries and then progresses in a way that is scarcely controllable, or completely uncontrollable. This article addresses the functional control mechanism of a biological organism, a comparison of techniques, and the way the negative feedback mechanisms fail in regulated feedback systems. The measurement and regulation system is controlled at the local, regional, and central levels in a biological system. Locally generated substances such as prostaglandins and hormones, as well as the central nervous system, play important roles in this process. Prostaglandins fulfil many conversion functions and are involved in vasoactive processes, pain, and inflammation. They play an intermediating role between the activity of the autonomic nervous system and local occurrences. The insufficiently explored conversion function of prostaglandins as a ubiquitously present cofactor may be related to the development of CRPS at sites which have had minor injuries in the past. Chronic Regional Pain Syndrome (CRPS) is a moderately prevalent disease, which occurs more frequently with age. Even though there are diseases known to have a precipitating effect on the aetiology of CRPS, for example Carpal tunnel syndrome, the mechanism of onset is unknown. The disease falls under the category of chronic pain, and seldom has an effective treatment based on scientific research. The economic and psychosocial aspects of the disease are substantial. CRPS is the final position of a positive feedback measurement and control system. Homoeostasis is directed by measurement and control processes. In electronics, a rapid conversion system, which quickly adapts to changing circumstances, superimposed with a delayed conversion system, which ensures a stable basis of homoeostasis. Measured changes are compensatorily controlled. An analogy is expected for a Complex Adaptive System

Changes in the Th1 : Th2 Cytokine Bias in Pregnancy and the Effects of the Anti-Inflammatory Cyclopentenone Prostaglandin 15-Deoxy-Δ12,14-Prostaglandin J2

Directory of Open Access Journals (Sweden)

Lynne Sykes

2012-01-01

Full Text Available Pregnancy is a complex immunological state in which a bias towards T helper 2 (Th2 protects the fetus. Evidence suggests that proinflammatory cytokines increase the risk of poor neonatal outcome, independently of the direct effect of preterm labour. The anti-inflammatory prostaglandin 15-deoxy-Δ12,14-Prostaglandin J2 (15dPGJ2 inhibits nuclear factor Kappa B (NF-κB in amniocytes and myocytes in vitro and is a ligand for the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2 receptor. Here we examine the Th1:Th2 cytokine bias in pregnancy and whether 15dPGJ2 could be used to inhibit the production of the proinflammatory cytokines through inhibition of NF-κB while simultaneously promoting Th2 interleukin 4 (IL-4 synthesis via CRTH2 in T helper cells. Peripheral blood mononuclear cells (PBMCs from women at 28 weeks, term pre-labour, term labour as well as non-pregnant female controls were cultured with 15dPGJ2 or vehicle control and stimulated with phorbol myristyl acetate (PMA/ionomycin. The percentage of CD4+ cells producing interferon gamma (IFN-γ and tumor necrosis factor alpha (TNF-α in response to PMA/ionomycin was significantly reduced in pregnancy. 15dPGJ2 reduced IFN-γ and TNF-α production in stimulated T helper cells, but did not alter IL-4 production in CRTH2+ve cells. 15dPGJ2 also reduced phospho-p65 in stimulated PBMCs. In summary, 15dPGJ2 suppresses the Th1 response of PBMCs during pregnancy and active labour whilst maintaining the Th2 response suggesting a therapeutic benefit in reducing neonatal morbidity in inflammation-induced PTL.

Genetic variation in the HSD17B1 gene and risk of prostate cancer.

Directory of Open Access Journals (Sweden)

Peter Kraft

2005-11-01

Full Text Available Steroid hormones are believed to play an important role in prostate carcinogenesis, but epidemiological evidence linking prostate cancer and steroid hormone genes has been inconclusive, in part due to small sample sizes or incomplete characterization of genetic variation at the locus of interest. Here we report on the results of a comprehensive study of the association between HSD17B1 and prostate cancer by the Breast and Prostate Cancer Cohort Consortium, a large collaborative study. HSD17B1 encodes 17beta-hydroxysteroid dehydrogenase 1, an enzyme that converts dihydroepiandrosterone to the testosterone precursor Delta5-androsterone-3beta,17beta-diol and converts estrone to estradiol. The Breast and Prostate Cancer Cohort Consortium researchers systematically characterized variation in HSD17B1 by targeted resequencing and dense genotyping; selected haplotype-tagging single nucleotide polymorphisms (htSNPs that efficiently predict common variants in U.S. and European whites, Latinos, Japanese Americans, and Native Hawaiians; and genotyped these htSNPs in 8,290 prostate cancer cases and 9,367 study-, age-, and ethnicity-matched controls. We found no evidence that HSD17B1 htSNPs (including the nonsynonymous coding SNP S312G or htSNP haplotypes were associated with risk of prostate cancer or tumor stage in the pooled multiethnic sample or in U.S. and European whites. Analyses stratified by age, body mass index, and family history of disease found no subgroup-specific associations between these HSD17B1 htSNPs and prostate cancer. We found significant evidence of heterogeneity in associations between HSD17B1 haplotypes and prostate cancer across ethnicity: one haplotype had a significant (p < 0.002 inverse association with risk of prostate cancer in Latinos and Japanese Americans but showed no evidence of association in African Americans, Native Hawaiians, or whites. However, the smaller numbers of Latinos and Japanese Americans in this study makes

Saliva, Serum Levels of Interleukin-21, -33 and Prostaglandin E2 in Patients with Generalised Aggressive or Chronic Periodontitis.

Science.gov (United States)

Gümüş, Pınar; Nizam, Nejat; Nalbantsoy, Ayşe; Özçaka, Özgün; Buduneli, Nurcan

This cross-sectional study aims to evaluate saliva, serum levels of interleukin-21 (IL-21), IL-33, and prostaglandin E2 (PGE2) in patients with generalised chronic periodontitis or aggressive periodontitis. Before initiation of any periodontal treatment, saliva and serum samples were collected and clinical periodontal measurements were recorded from 94 participants (25 aggressive periodontitis patients, 25 chronic periodontitis patients, 44 periodontally healthy individuals). IL-21, IL-33 and PGE2 levels in serum and saliva samples were determined by ELISA. Data were tested statistically using Kruskal-Wallis, Mann-Whitney U-, and Spearman-rho rank tests. Saliva IL-33 levels were statistically significantly higher in the chronic than the aggressive group (p periodontitis groups. Saliva IL-33 levels correlated with age in the chronic periodontitis group (p periodontitis groups (p chronic and aggressive periodontitis, but the present findings support the role of these cytokines in periodontitis. Statistically significantly higher saliva IL-33 levels in the chronic periodontitis group warrant further research.

Distribution of flux-pinning energies in YBa2Cu3O(7-delta) and Bi2Sr2CaCu2O(8+delta) from flux noise

Science.gov (United States)

Ferrari, M. J.; Johnson, Mark; Wellstood, Frederick C.; Clarke, John; Mitzi, D.

1990-01-01

The spectral density of the magnetic flux noise measured in high-temperature superconductors in low magnetic fields scales approximately as the inverse of the frequency and increases with temperature. The temperature and frequency dependence of the noise are used to determine the pinning energies of individual flux vortices in thermal equilibrium. The distribution of pinning energies below 0.1 eV in YBa(2)Cu(3)O(7-delta) and near 0.2 eV in Bi(2)Sr(2)CaCu(2)O(8+delta). The noise power is proportional to the ambient magnetic field, indicating that the vortex motion is uncorrelated.

In vivo metabolism of the methyl homologues of delta-8-tetrahydrocannabinol, delta-9-tetrahydrocannabinol and abn-delta-8-tetrahydrocannabinol in the mouse.

Science.gov (United States)

Brown, N K; Harvey, D J

1988-04-01

Methyl-delta-8-tetrahydrocannabinol (methyl-delta-8-THC), methyl-delta-9-THC and abn-methyl-delta-8-THC were synthesized by condensation of orcinol and (1S)-cis-verbenol and were administered to male Charles River CD-1 mice. Extracted hepatic metabolites were isolated by chromatography on Sephadex LH-20 and examined by gas chromatography/mass spectrometry as trimethylsilyl (TMS), (2H9)TMS and methyl ester/TMS derivatives. In addition, metabolic fractions were reduced with lithium aluminium deuteride to convert carboxylic acids to alcohols for structural correlation. Metabolites from methyl-delta-8-THC were similar with respect to the positions substituted to those produced by higher homologues; the major metabolite was methyl-delta-8-THC-11-oic acid. abn-Methyl-delta-8-THC was metabolized in a different manner. The location of the aromatic methyl group at the position adjacent to ring fusion appeared to inhibit metabolism at C(11) to a considerable extent and also to reduce the amount of the resulting alcohol from being oxidized to a carboxylic acid. This caused other metabolic pathways to become dominant, with the result that a compound containing a hydroxy group at the gem-methyl position was the major metabolite. Hydroxylation at this position has not been confirmed with any other cannabinoid, although it is thought to result in trace concentrations of hydroxy metabolites from some compounds. Metabolism of methyl-delta-9-THC was also similar to that of the higher homologues, with the exception that less metabolism occurred at C(8) and a higher percentage of the total metabolic fraction was accounted for by the 11-oic acid metabolite. Minor metabolites were mainly dihydroxy compounds and hydroxylated derivatives of delta-9-THC-11-oic acid.

Improved stability and performance from sigma-delta modulators using 1-bit vector quantization

DEFF Research Database (Denmark)

Risbo, Lars

1993-01-01

A novel class of sigma-delta modulators is presented. The usual scalar 1-b quantizer in a sigma-delta modulator is replaced by a 1-b vector quantizer with a N-dimensional input state-vector from the linear feedback filter. Generally, the vector quantizer changes the nonlinear dynamics...... of the modulator, and a proper choice of vector quantizer can improve both system stability and coding performance. It is shown how to construct the vector quantizer in order to limit the excursions in state-space. The proposed method is demonstrated graphically for a simple second-order modulator...

A protein-targeting strategy used to develop a selective inhibitor of the E17K point mutation in the PH domain of Akt1

Science.gov (United States)

Deyle, Kaycie M.; Farrow, Blake; Qiao Hee, Ying; Work, Jeremy; Wong, Michelle; Lai, Bert; Umeda, Aiko; Millward, Steven W.; Nag, Arundhati; Das, Samir; Heath, James R.

2015-05-01

Ligands that can bind selectively to proteins with single amino-acid point mutations offer the potential to detect or treat an abnormal protein in the presence of the wild type (WT). However, it is difficult to develop a selective ligand if the point mutation is not associated with an addressable location, such as a binding pocket. Here we report an all-chemical synthetic epitope-targeting strategy that we used to discover a 5-mer peptide with selectivity for the E17K-transforming point mutation in the pleckstrin homology domain of the Akt1 oncoprotein. A fragment of Akt1 that contained the E17K mutation and an I19[propargylglycine] substitution was synthesized to form an addressable synthetic epitope. Azide-presenting peptides that clicked covalently onto this alkyne-presenting epitope were selected from a library using in situ screening. One peptide exhibits a 10:1 in vitro selectivity for the oncoprotein relative to the WT, with a similar selectivity in cells. This 5-mer peptide was expanded into a larger ligand that selectively blocks the E17K Akt1 interaction with its PIP3 (phosphatidylinositol (3,4,5)-trisphosphate) substrate.

Areca nut components stimulate ADAM17, IL-1α, PGE2 and 8-isoprostane production in oral keratinocyte: role of reactive oxygen species, EGF and JAK signaling.

Science.gov (United States)

Chang, Mei-Chi; Chan, Chiu-Po; Chen, Yi-Jane; Hsien, Hsiang-Chi; Chang, Ya-Ching; Yeung, Sin-Yuet; Jeng, Po-Yuan; Cheng, Ru-Hsiu; Hahn, Liang-Jiunn; Jeng, Jiiang-Huei

2016-03-29

Betel quid (BQ) chewing is an etiologic factor of oral submucous fibrosis (OSF) and oral cancer. There are 600 million BQ chewers worldwide. The mechanisms for the toxic and inflammatory responses of BQ are unclear. In this study, both areca nut (AN) extract (ANE) and arecoline stimulated epidermal growth factor (EGF) and interleukin-1α (IL-1α) production of gingival keratinocytes (GKs), whereas only ANE can stimulate a disintegrin and metalloproteinase 17 (ADAM17), prostaglandin E2 (PGE2) and 8-isoprostane production. ANE-induced EGF production was inhibited by catalase. Addition of anti-EGF neutralizing antibody attenuated ANE-induced cyclooxygenase-2 (COX-2), mature ADAM9 expression and PGE2 and 8-isoprostane production. ANE-induced IL-1α production was inhibited by catalase, anti-EGF antibody, PD153035 (EGF receptor antagonist) and U0126 (MEK inhibitor) but not by α-naphthoflavone (cytochrome p450-1A1 inhibitor). ANE-induced ADAM17 production was inhibited by pp2 (Src inhibitor), U0126, α-naphthoflavone and aspirin. AG490 (JAK inhibitor) prevented ANE-stimulated ADAM17, IL-1α, PGE2 production, COX-2 expression, ADAM9 maturation, and the ANE-induced decline in keratin 5 and 14, but showed little effect on cdc2 expression and EGF production. Moreover, ANE-induced 8-isoprostane production by GKs was inhibited by catalase, anti-EGF antibody, AG490, pp2, U0126, α-naphthoflavone, Zinc protoporphyrin (ZnPP) and aspirin. These results indicate that AN components may involve in BQ-induced oral cancer by induction of reactive oxygen species, EGF/EGFR, IL-1α, ADAMs, JAK, Src, MEK/ERK, CYP1A1, and COX signaling pathways, and the aberration of cell cycle and differentiation. Various blockers against ROS, EGF, IL-1α, ADAM, JAK, Src, MEK, CYP1A1, and COX can be used for prevention or treatment of BQ chewing-related diseases.

Improved γ-linolenic acid production in Mucor circinelloides by homologous overexpressing of delta-12 and delta-6 desaturases.

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Zhang, Yao; Luan, Xiao; Zhang, Huaiyuan; Garre, Victoriano; Song, Yuanda; Ratledge, Colin

2017-06-21

γ-Linolenic acid (GLA) is important because of its nutritional value and medicinal applications. Although the biosynthetic pathways of some plant and microbial GLA have been deciphered, current understanding of the correlation between desaturases and GLA synthesis in oleaginous fungi is incomplete. In previous work, we found that a large amount of oleic acid (OA) had not been converted to linoleic acid (LA) or GLA in Mucor circinelloides CBS 277.49, which may be due to inadequate activities of the delta-12 or delta-6 desaturases, and thus leading to the accumulation of OA and LA. Thus, it is necessary to explore the main contributing factor during the process of GLA biosynthesis in M. circinelloides. To enhance GLA production in M. circinelloides, homologous overexpression of delta-12 and two delta-6 desaturases (named delta-6-1 and delta-6-2, respectively) were analyzed. When delta-6 desaturase were overexpressed in M. circinelloides, up to 43% GLA was produced in the total fatty acids, and the yield of GLA reached 180 mg/l, which were, respectively, 38 and 33% higher than the control strain. These findings revealed that delta-6 desaturase (especially for delta-6-1 desaturase) plays an important role in GLA synthesis by M. circinelloides. The strain overexpressing delta-6-1 desaturase may have potential application in microbial GLA production.

Prostaglandin E2 Prevents Hyperosmolar-Induced Human Mast Cell Activation through Prostanoid Receptors EP2 and EP4

Science.gov (United States)

Torres-Atencio, Ivonne; Ainsua-Enrich, Erola; de Mora, Fernando; Picado, César; Martín, Margarita

2014-01-01

Background Mast cells play a critical role in allergic and inflammatory diseases, including exercise-induced bronchoconstriction (EIB) in asthma. The mechanism underlying EIB is probably related to increased airway fluid osmolarity that activates mast cells to the release inflammatory mediators. These mediators then act on bronchial smooth muscle to cause bronchoconstriction. In parallel, protective substances such as prostaglandin E2 (PGE2) are probably also released and could explain the refractory period observed in patients with EIB. Objective This study aimed to evaluate the protective effect of PGE2 on osmotically activated mast cells, as a model of exercise-induced bronchoconstriction. Methods We used LAD2, HMC-1, CD34-positive, and human lung mast cell lines. Cells underwent a mannitol challenge, and the effects of PGE2 and prostanoid receptor (EP) antagonists for EP1–4 were assayed on the activated mast cells. Beta-hexosaminidase release, protein phosphorylation, and calcium mobilization were assessed. Results Mannitol both induced mast cell degranulation and activated phosphatidyl inositide 3-kinase and mitogen-activated protein kinase (MAPK) pathways, thereby causing de novo eicosanoid and cytokine synthesis. The addition of PGE2 significantly reduced mannitol-induced degranulation through EP2 and EP4 receptors, as measured by beta-hexosaminidase release, and consequently calcium influx. Extracellular-signal-regulated kinase 1/2, c-Jun N-terminal kinase, and p38 phosphorylation were diminished when compared with mannitol activation alone. Conclusions Our data show a protective role for the PGE2 receptors EP2 and EP4 following osmotic changes, through the reduction of human mast cell activity caused by calcium influx impairment and MAP kinase inhibition. PMID:25329458

Stable isotope deltas: Tiny, yet robust signatures in nature

Science.gov (United States)

Brand, Willi A.; Coplen, Tyler B.

2012-01-01

Although most of them are relatively small, stable isotope deltas of naturally occurring substances are robust and enable workers in anthropology, atmospheric sciences, biology, chemistry, environmental sciences, food and drug authentication, forensic science, geochemistry, geology, oceanography, and paleoclimatology to study a variety of topics. Two fundamental processes explain the stable isotope deltas measured in most terrestrial systems: isotopic fractionation and isotope mixing. Isotopic fractionation is the result of equilibrium or kinetic physicochemical processes that fractionate isotopes because of small differences in physical or chemical properties of molecular species having different isotopes. It is shown that the mixing of radioactive and stable isotope end members can be modelled to provide information on many natural processes, including 14C abundances in the modern atmosphere and the stable hydrogen and oxygen isotopic compositions of the oceans during glacial and interglacial times. The calculation of mixing fractions using isotope balance equations with isotope deltas can be substantially in error when substances with high concentrations of heavy isotopes (e.g. 13C, 2H, and 18O ) are mixed. In such cases, calculations using mole fractions are preferred as they produce accurate mixing fractions. Isotope deltas are dimensionless quantities. In the International System of Units (SI), these quantities have the unit 1 and the usual list of prefixes is not applicable. To overcome traditional limitations with expressing orders of magnitude differences in isotope deltas, we propose the term urey (symbol Ur), after Harold C. Urey, for the unit 1. In such a manner, an isotope delta value expressed traditionally as−25 per mil can be written as−25 mUr (or−2.5 cUr or−0.25 dUr; the use of any SI prefix is possible). Likewise, very small isotopic differences often expressed in per meg ‘units’ are easily included (e.g. either+0.015 ‰ or+15 per meg

One-Day Use of Preoperative Topical Nonsteroidal Anti-Inflammatory Drug Prevents Intraoperative Prostaglandin Level Elevation During Femtosecond Laser-Assisted Cataract Surgery.

Science.gov (United States)

Kiss, Huba J; Takacs, Agnes I; Kranitz, Kinga; Sandor, Gabor L; Toth, Gabor; Gilanyi, Beatrix; Nagy, Zoltan Z

2016-08-01

To determine if pretreatment with topical nonsteroidal anti-inflammatory drug (NSAID) prior to femtosecond laser-assisted cataract surgery (FLACS) prevents intraoperative prostaglandin level elevation as a potential risk factor of postoperative complications. Thirty-six patients with clinically significant cataract and without any concomitant general or ophthalmic disease were enrolled into the three age-matched groups of the study. The mean age of the patients was 62.3 ± 13.1 years. The first group of patients underwent traditional phacoemulsification (Control group), on the second group of patients FLACS was performed, and the third group of patients received topical 0.1% nepafenac pretreatment for 1one day prior to FLACS. Before the phacoemulsification part of the cataract surgery, approximately 110 µL of aqueous humor was collected in all groups. Total prostaglandin concentrations of the collected aqueous humor samples were evaluated by enzyme immunoassay (EIA). The mean of the total prostaglandin concentrations of the aqueous humor samples was 208.8 ± 140.5 pg/mL in patients in the control group, 1449.1 ± 1019.7 pg/mL in the FLACS group (p > 0.001), and 92.2 ± 51.7 pg/mL in the group pretreated with topical NSAID before the FLACS (p > 0.001 compared to FLACS; p > 0.01 compared to control), respectively. FLACS surgery increases intracameral prostaglandin concentration. However, using preoperative 1-day-long nonsteroid anti-inflammatory drops prior to FLACS, this intraoperative increase diminishes. Our study raises the possibility that NSAID pretreatment may be routinely administered before FLACS cataract surgeries to achieve a further decrease in the potential complications of increased total prostaglandin concentration during FLACS surgeries.

Mice lacking prostaglandin E receptor subtype 4 manifest disrupted lipid metabolism attributable to impaired triglyceride clearance.

Science.gov (United States)

Cai, Yin; Ying, Fan; Song, Erfei; Wang, Yu; Xu, Aimin; Vanhoutte, Paul M; Tang, Eva Hoi-Ching

2015-12-01

Upon high-fat feeding, prostaglandin E receptor subtype 4 (EP4)-knockout mice gain less body weight than their EP4(+/+) littermates. We investigated the cause of the lean phenotype. The mice showed a 68.8% reduction in weight gain with diminished fat mass that was not attributable to reduced food intake, fat malabsorption, or increased energy expenditure. Plasma triglycerides in the mice were elevated by 244.9%. The increase in plasma triglycerides was independent of changes in hepatic very low density lipoprotein (VLDL)-triglyceride production or intestinal chylomicron-triglyceride synthesis. However, VLDL-triglyceride clearance was drastically impaired in the EP4-knockout mice. The absence of EP4 in mice compromised the activation of lipoprotein lipase (LPL), the key enzyme responsible for trafficking of plasma triglycerides into peripheral tissues. Deficiency in EP4 reduced hepatic mRNA expression of the transcriptional factor cAMP response element binding protein H (by 36.8%) and LPL activators, including apolipoprotein (Apo)a5 (by 40.2%) and Apoc2 (by 61.3%). In summary, the lean phenotype of EP4-deficient mice resulted from reduction in adipose tissue and accretion of other peripheral organs caused by impaired triglyceride clearance. The findings identify a new metabolic dimension in the physiologic role played by endogenous EP4. © FASEB.

Coherent diffusive transport mediated by Andreev reflections at V=Delta/e in a mesoscopic superconductor/semiconductor/superconductor junction

DEFF Research Database (Denmark)

Kutchinsky, Jonatan; Taboryski, Rafael Jozef; Kuhn, Oliver

1997-01-01

We present experiments revealing a singularity in the coherent current across a superconductor/semiconductor/superconductor (SSmS) junction at the bias voltage corresponding to the superconducting energy gap V=Delta/e. The SSmS structure consists of highly doped GaAs with superconducting electrodes...

The potential energy of an infinite system of nucleons and delta resonances

International Nuclear Information System (INIS)

Goodwin, N.H.

1980-01-01

The nature and properties of the delta resonance, Δ (1236), in infinite nuclear and neutron matter are investigated. Calculations of the potential energy of a system of separate Fermi seas of nucleons and delta resonances have been performed using Jastrow lowest-order constrained variational techniques. Using the Reid soft-core nucleon-nucleon interaction and a model, consistent, energy-dependent, static one-pion- and one-rho-meson-exchange nucleon-delta potential, a significant reduction in the potential energy of the system is found at densities above nuclear matter density (0.17 fm -3 ) when deltas are present. The density at which the formation of a separate Fermi sea of deltas is favourable is estimated and the consequences for the possible formation of a pion condensate and the properties of neutron star matter are discussed. (author)

Enhancing the understanding of earthworm feeding behaviour via the use of fatty acid delta13C values determined by gas chromatography-combustion-isotope ratio mass spectrometry.

Science.gov (United States)

Dungait, Jennifer A J; Briones, Maria J I; Bol, Roland; Evershed, Richard P

2008-06-01

Litter-dwelling (epigeic) Lumbricus rubellus and soil-dwelling (endogeic) Allolobophora chlorotica earthworms were observed aggregating under C(3) (delta(13)C = -31.3 per thousand; delta(15)N = 10.7 per thousand) and C(4) (delta(13)C = -12.6 per thousand; delta(15)N = 7.5 per thousand) synthetic dung pats applied to a temperate grassland (delta(13)C = -30.3 per thousand; delta(15)N = 5.7 per thousand) in an experiment carried out for 372 days. Bulk delta(13)C values of earthworms collected from beneath either C(3) or C(4) dung after 28, 56, 112 and 372 days demonstrated that (i) L. rubellus beneath C(4) dung were significantly (13)C-enriched after 56 days (delta(13)C = -23.8 per thousand) and 112 days (delta(13)C = -22.4 per thousand) compared with those from C(3) dung treatments (56 days, delta(13)C = -26.5 per thousand; 112 days, delta(13)C = -27.0 per thousand), and (ii) A. chlorotica were 2.1 per thousand (13)C-enriched (delta(13)C = -24.2 per thousand) relative to those from C(3) dung (delta(13)C = -26.3 per thousand) treatments after 372 days. Bulk delta(15)N values did not suggest significant uptake of dung N by either species beneath C(3) or C(4) dung, but showed that the endogeic species (total mean delta(15)N = 3.3 per thousand) had higher delta(15)N values than the epigeic species (total mean delta(15)N = 5.4 per thousand). Although the two species exhibited similar fatty acid profiles, individual fatty acid delta(13)C values revealed extensive routing of dietary C into body tissue of L. rubellus, but minor incorporation into A. chlorotica. In particular, the direct incorporation of microbial biomarker fatty acids (iC(17:0), aC(17:0)) from (13)C-labelled dung in situ, the routing of dung C into de novo synthesised compounds (iC(20:4)(omega)(6),C(20:5)(omega)(3), and the assimilation of essential fatty acids ((C(18:1)(omega)(9), C(18:1)(omega(7), C(18:2)(omega(6), C(18:3)(omega)(3)) derived from dung, were determined. John Wiley & Sons, Ltd

Beam-helicity associated electroproduction of real photons ep {yields} e{gamma}{pi}N in the {Delta}-resonance region

Energy Technology Data Exchange (ETDEWEB)