Enzyme-Inducing Antiseizure Drug Use Is Associated with Long-Term Cardiovascular Disease in a Dose Dependent Fashion in Adults with Epilepsy

2021 ◽  
Author(s):  
Colin Bruce Josephson ◽  
Samuel Wiebe ◽  
Guillermo Delgado-Garcia ◽  
Arturo González-Izquierdo ◽  
Spiros Denaxas ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Drug Use ◽  
Dose Dependent Fashion ◽  
Dose Dependent

Salt sensitivity in hypertensive rats with angiotensin II administration

1990 ◽  
Vol 259 (5) ◽  
pp. R1012-R1016 ◽  
Author(s):  
K. Ando ◽  
Y. Sato ◽  
T. Fujita
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Salt Sensitivity ◽  
Ang Ii ◽  
Short Term ◽  
Salt Loading ◽  
Salt Diet ◽  
Dose Dependent Fashion ◽  
Dose Dependent

We examined the salt sensitivity of blood pressure in angiotensin II (ANG II)-induced hypertension. Wistar rats, salt loaded (0.66, 2, or 8% salt-containing diet) for 4 or 12 days, were infused intravenously with 15 or 60 ng/min of ANG II. Systolic blood pressure (SBP) was not increased by long-term (12 days) salt loading, and SBP was unchanged with ANG II and normal-salt (0.66%) diet. However, when combined with salt loading, ANG II produced hypertension in a dose-dependent fashion; compared with control (120 +/- 2 mmHg), SBP was increased with 15 ng/min of ANG II and 8% salt diet (145 +/- 5 mmHg, P less than 0.05) and with 60 ng/min of ANG II and either 2 or 8% salt diet (149 +/- 8 and 174 +/- 8 mmHg, P less than 0.05, respectively). Na space (exchangeable Na) was increased in a roughly similar pattern and correlated significantly (r = 0.531, P less than 0.05) with SBP. However, with 15 ng/min of ANG II, Na space was not different among rats on either level of salt loading, although the 8% salt diet elevated SBP. Data obtained with short-term (4 days) treatment indicate that an elevated Na space preceded development of hypertension. With 15 ng/min of ANG II and 8% salt diet for 4 days, Na space was markedly (P less than 0.05) increased, but SBP was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Association of Enzyme-Inducing Antiseizure Drug Use With Long-term Cardiovascular Disease

2021 ◽  
Author(s):  
Colin B. Josephson ◽  
Samuel Wiebe ◽  
Guillermo Delgado-Garcia ◽  
Arturo Gonzalez-Izquierdo ◽  
Spiros Denaxas ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Drug Use

scholarly journals The anti-oestrogen ICI 182,780, but not tamoxifen, inhibits the growth of MCF-7 breast cancer cells refractory to long-term oestrogen deprivation through down-regulation of oestrogen receptor and IGF signalling

2005 ◽  
Vol 12 (4) ◽  
pp. 1017-1036 ◽  
Author(s):  
L-A Martin ◽  
S Pancholi ◽  
C M W Chan ◽  
I Farmer ◽  
C Kimberley ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Ici 182,780 ◽  
Growth Factor Signalling ◽  
Er Positive ◽  
Dose Dependent Fashion ◽  
And Function ◽  
Dose Dependent ◽  
Mcf 7

Long-term culture of MCF-7 wild-type (wt) cells in steroid-depleted medium (LTED) results in hypersensitivity to oestradiol (E2) coinciding with elevated levels of ERα and enhanced growth factor signalling. In this study, we aimed to compare the effects of the pure anti-oestrogen ICI 182,780 (ICI) with the competitive anti-oestrogen tamoxifen (TAM) on oestrogen and IGF signalling in these cells. Wt MCF-7 and LTED cells were treated with a log 7 concentration range of E2, TAM or ICI. Effects on cell growth, ERα transactivation, expression of ERα, ERβ and components of the IGF pathway were measured with and without insulin. In the presence of insulin, growth of LTED cells was refractory to TAM but inhibited by ICI and E2. In the absence of insulin, LTED cells showed persistent hypersensitivity to E2, and remained inhibited by ICI but were largely unaffected by TAM. ICI but not TAM inhibited ER-mediated gene transcription and treatment with ICI resulted in a dose-dependent reduction in ERα levels whilst having no effect on ERβ expression. IGF-I receptor and insulin receptor substrate 2 levels were increased in LTED versus the Wt MCF-7 cells, and ICI but not TAM reduced their expression in a dose-dependent fashion. Thus IGF signalling as well as ERα expression and function are enhanced during LTED. While the resultant cells are resistant to TAM, ICI down-regulates ERα, reducing IGF signalling and cell growth. These results support the use of ICI in women with ER-positive breast cancer who have relapsed on an aromatase inhibitor.

Donor treatment with pegylated G-CSF augments the generation of IL-10-producing regulatory T cells and promotes transplantation tolerance

Blood ◽  
2004 ◽  
Vol 103 (9) ◽  
pp. 3573-3581 ◽  
Author(s):  
Edward S. Morris ◽  
Kelli P. A. MacDonald ◽  
Vanessa Rowe ◽  
Diana H. Johnson ◽  
Tatjana Banovic ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Interleukin 10 ◽  
Term Survival ◽  
Donor T Cells ◽  
Dose Dependent Fashion ◽  
Dose Dependent ◽  
Donor Pretreatment

Abstract We investigated whether the protection from graft-versus-host disease (GVHD) afforded by donor treatment with granulocyte colony-stimulating factor (G-CSF) could be enhanced by dose escalation. Donor treatment with human G-CSF prevented GVHD in the B6 → B6D2F1 murine model in a dose-dependent fashion, and murine G-CSF provided equivalent protection from GVHD at 10-fold lower doses. Donor pretreatment with a single dose of pegylated G-CSF (peg-G-CSF) prevented GVHD to a significantly greater extent than standard G-CSF (survival, 75% versus 11%, P < .001). Donor T cells from peg-G-CSF-treated donors failed to proliferate to alloantigen and inhibited the responses of control T cells in an interleukin 10 (IL-10)-dependent fashion in vitro. T cells from peg-G-CSF-treated IL-10-/- donors induced lethal GVHD; T cells from peg-G-CSF-treated wild-type (wt) donors promoted long-term survival. Whereas T cells from peg-G-CSF wt donors were able to regulate GVHD induced by T cells from control-treated donors, T cells from G-CSF-treated wt donors and peg-G-CSF-treated IL-10-/- donors did not prevent mortality. Thus, peg-G-CSF is markedly superior to standard G-CSF for the prevention of GVHD following allogeneic stem cell transplantation (SCT), due to the generation of IL-10-producing regulatory T cells. These data support prospective clinical trials of peg-G-CSF-mobilized allogeneic blood SCT. (Blood. 2004;103:3573-3581)

FOLLICLE FORMATION AND IODIDE METABOLISM IN CULTURES OF HUMAN THYROID CELLS

1981 ◽  
Vol 90 (1) ◽  
pp. 113-NP ◽  
Author(s):  
J. G. DICKSON ◽  
S. HOVSÉPIAN ◽  
G. FAYET ◽  
S. LISSITZKY
Keyword(s):  
Primary Cultures ◽  
Genetic Defect ◽  
Thyroid Tissue ◽  
Calf Serum ◽  
Human Thyroid ◽  
Thyroid Cells ◽  
Dose Dependent Fashion ◽  
Dose Dependent

Primary cultures were initiated using thyroid tissue obtained at operation from patients with Graves's disease. The in-vitro conditions which permitted the formation of functional follicular structures in both primary cultures and derived sub-cultures were examined. In both situations, culture without the addition of calf serum to the medium resulted in the formation of follicles in response to thyrotrophin. In primary cultures the response to stimulation by exogenous thyrotrophin was variable. However, cells derived from long-term primary monolayers responded to thyrotrophin stimulation in a more predictable manner. In sub-cultures, the ability of cells to concentrate and organify iodide was augmented in a dose-dependent fashion in response to thyrotrophin (0 to 0·2 mu./ml); maximal values of 20 to 80 times those of control cultures being obtained. While follicular structure was maintained at higher hormone concentrations, iodide-trapping capacity declined. Similar effects were produced by both low and high purity thyrotrophin and by dibutyryl cyclic AMP. Thyroid cells from two patients with a genetic defect of iodide organification exhibited the same lesion in vitro.

Plasminogen Interactions with Immobilized Fibrinogen

1989 ◽  
Vol 62 (04) ◽  
pp. 1078-1082 ◽  
Author(s):  
Burt Adelman ◽  
Patricia Ouynn
Keyword(s):  
Immunosorbent Assay ◽  
Aminocaproic Acid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Binding Regions ◽  
Dose Dependent Fashion ◽  
Epsilon Aminocaproic Acid ◽  
Dose Dependent

SummaryThis report describes the binding of plasminogen to fibrinogen adsorbed onto polystyrene wells. Binding was determined by enzyme linked immunosorbent assay. Both glu- and lys-plasminogen bound to immobilized fibrinogen in a dose-dependent fashion. However, more lys- than glu-plasminogen bound when equal concentrations of either were added to immobilized fibrinogen. Plasminogen binding was inhibited by epsilon aminocaproic acid indicating that binding was mediated via lysine-binding regions of plasminogen. Soluble fibrinogen added in excess of immobilized fibrinogen did not compete for plasminogen binding but fibrinogen fragments produced by plasmin digestion of fibrinogen did. Treatment of immobilized fibrinogen with thrombin caused a small but significant (p <0.01) increase in plasminogen binding. These studies demonstrate that immobilized fibrinogen binds both glu- and lys-plasminogen and that binding is mediated via lysine-binding regions. These interactions may facilitate plasminogen binding to fibrinogen adsorbed on to surfaces and to cells such as platelets which bind fibrinogen.

Soluble Thrombomodulin Purified from Human Urine Exhibits a Potent Anticoagulant Effect In Vitro and In Vivo

1995 ◽  
Vol 73 (05) ◽  
pp. 805-811 ◽  
Author(s):  
Yasuo Takahashi ◽  
Yoshitaka Hosaka ◽  
Hiromi Niina ◽  
Katsuaki Nagasawa ◽  
Masaaki Naotsuka ◽  
...  
Keyword(s):  
Human Urine ◽  
Specific Activity ◽  
Anticoagulant Activity ◽  
Rabbit Lung ◽  
Soluble Thrombomodulin ◽  
Molecular Weights ◽  
Dose Dependent Fashion ◽  
Dose Dependent

SummaryWe examined the anticoagulant activity of two major molecules of soluble thrombomodulin purified from human urine. The apparent molecular weights of these urinary thrombomodulins (UTMs) were 72,000 and 79,000, respectively. Both UTMs showed more potent cofactor activity for protein C activation [specific activity >5,000 thrombomodulin units (TMU)/mg] than human placental thrombomodulin (2,180 TMU/mg) and rabbit lung thrombomodulin (1,980 TMU/mg). The UTMs prolonged thrombin-induced fibrinogen clotting time (>1 TMU/ml), APTT (>5 TMU/ml), TT (>5 TMU/ml) and PT (>40 TMU/ml) in a dose-dependent fashion. These effects appeared in the concentration range of soluble thrombomodulins present in human plasma and urine. In the rat DIC model induced by thromboplastin, administration of UTMs by infusion (300-3,000 TMU/kg) restored the hematological abnormalities derived from DIC in a dose-dependent fashion. These results demonstrate that UTMs exhibit potent anticoagulant and antithrombotic activities, and could play a physiologically important role in microcirculation.

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