Low Dose Poly I:C Prevents Diabetes in the Diabetes Prone BB Rat

1998 ◽  
Vol 11 (4) ◽  
pp. 343-352 ◽  
Author(s):  
Douglas O Sobel ◽  
Deepshika Goyal ◽  
Behrouz Ahvazi ◽  
Ji-Won Yoon ◽  
Young Hwa Chung ◽  
...  
Keyword(s):  
Low Dose ◽  
Poly I:C ◽  
Bb Rat

scholarly journals Synergistic benefit in inflammatory arthritis by targeting IκB kinase ϵ and interferon β

2008 ◽  
Vol 68 (2) ◽  
pp. 257-263 ◽  
Author(s):  
M Corr ◽  
D L Boyle ◽  
L Ronacher ◽  
N Flores ◽  
G S Firestein
Keyword(s):  
Gene Expression ◽  
Low Dose ◽  
Serum Levels ◽  
Poly I:C ◽  
Type I ◽  
Wild Type ◽  
Polycytidylic Acid ◽  
Iκb Kinase ◽  
Novel Approach ◽  
Clinical Arthritis

Objectives:The IκB kinase (IKK)-related kinase IKKϵ regulates type I interferon expression and responses as well as proinflammatory mediator production. We examined the role of IKKϵ in arthritis and its ability to enhance the therapeutic response to systemic interferon (IFN) β therapy in passive murine K/BxN arthritis.Methods:IKKϵ–/–, IFNα∼βR–/– and wild type mice were given K/BxN serum and treated with polyinosinic polycytidylic acid (poly(I:C)), IFNβ, or normal saline. Clinical response and histological scores were assessed. Gene expression in the paws was measured by quantitative PCR. Serum interleukin 1a receptor agonist (IL1Ra) and IL10 were measured by ELISA and multiplex bead array.Results:Arthritis was almost completely blocked in wild type mice if arthritogenic K/BxN serum and the Toll-like receptor (TLR)3 ligand, poly(I:C), were coadministered at the onset of the model, but not in established disease. Mice deficient in IFNα∼βR had an accelerated course of arthritis, and did not respond to poly(I:C). IKKϵ null mice had a modest decrease in clinical arthritis compared with heterozygous mice. Low doses of IFNβ that were ineffective in wild type mice significantly decreased clinical arthritis in IKKϵ null mice. Articular chemokine gene expression was reduced in the IKKϵ–/– mice with arthritis and secreted IL1Ra (sIL1Ra) mRNA was significantly increased. Serum levels of IL1Ra were increased in low dose IFNβ-treated IKKϵ–/– mice.Conclusions:Subtherapeutic doses of IFNβ enhance the anti-inflammatory effects of IKKϵ deficiency, possibly by increasing production of IL1Ra and unmasking the antichemokine effects. Combination therapy with low dose IFNβ and an IKKϵ inhibitor might improve efficacy of either agent alone and offers a novel approach to RA.

Poly I:C accelerates development of diabetes mellitus in diabetes-prone BB rat

Diabetes ◽  
1992 ◽  
Vol 41 (8) ◽  
pp. 1016-1021 ◽  
Author(s):  
C. H. Ewel ◽  
D. O. Sobel ◽  
B. J. Zeligs ◽  
J. A. Bellanti
Keyword(s):  
Diabetes Mellitus ◽  
Poly I:C ◽  
Bb Rat

scholarly journals The Optimal Condition of Poly(I: C)-Induced Knockout of Cre Recombinase for Mx1-Cre/ Cre-loxP Mice

2021 ◽  
Author(s):  
Bijie Yang ◽  
Haobiao Wang ◽  
Yuanyuan Liu ◽  
Feifei Xiao ◽  
Mei Kuang ◽  
...  
Keyword(s):  
Survival Rate ◽  
Knockout Mice ◽  
Low Dose ◽  
Gene Knockout ◽  
Conditional Knockout ◽  
Poly I:C ◽  
High Dose ◽  
P System ◽  
Single High Dose ◽  
Pure Poly

Abstract BackgroundThe Cre-loxP system is widely applied for conditional knockout mice, commonly used to study the function of specific genes. Although some different promoters drive Cre expression, the poly(I: C)-inducible Mx1-Cre is the most commonly used to delete the target gene in experimental hematology. However, the optimal induction knockout condition for Mx1-Cre/ Cre-loxP mice using the Poly(I:C)-inducible Cre-loxP conditional system remains unclear. Here, we present two different components and three injection protocols of poly(I: C) to find the optimized condition. ResultsThe results showed that the better knockout efficiency of Cre-loxP in mice injected with pure poly(I: C) has than those injected with poly(I: C) with some components. From the perspective of lethal genes (Brg1), data showed that mice injected with a single high dose (500 µg) of pure Poly (I:C) had a lower knockout rate. For mice injected media-dose (10µg/g) poly(I: C) triple, which induced a high knockout rate, but the mortality rate was still high. Importantly, the mice injected low-dose (6µg/g) poly(I: C) triple, both the knockout rate and survival rate of mice was high. Similarly, the knockout rate of non-lethal mice injected with media-dose (10µg/g) or low-dose (6μg/g) poly(I: C) triple was very high, but injected with a single high dose (500 µg) of pure poly(I: C) had a low knockout rate. ConclusionOur studies provided the optimized condition for using poly(I: C)-inducible effective knockout and maintaining the survival rate for the Cre-loxP mice, which might be applied in other knockout mice for this system to ensure both the gene knockout and the mice survival.

The role of NK cell activity in the pathogenesis of poly I:C accelerated and spontaneous diabetes in the diabetes prone BB rat

1995 ◽  
Vol 8 (6) ◽  
pp. 843-857 ◽  
Author(s):  
D SOBEL ◽  
N AZUMI ◽  
K CRESWELL ◽  
D HOLTERMAN ◽  
O BLAIR ◽  
...  
Keyword(s):  
Nk Cell ◽  
Cell Activity ◽  
Spontaneous Diabetes ◽  
Poly I:C ◽  
Bb Rat ◽  
Nk Cell Activity

Poly I:C Accelerates Development of Diabetes Mellitus in Diabetes-Prone BB Rat

Diabetes ◽  
1992 ◽  
Vol 41 (8) ◽  
pp. 1016-1021 ◽  
Author(s):  
C. H. Ewel ◽  
D. O. Sobel ◽  
B. J. Zeligs ◽  
J. A. Bellanti
Keyword(s):  
Diabetes Mellitus ◽  
Poly I:C ◽  
Bb Rat

Poly I:C Induces Development of Diabetes Mellitus in BB Rat

Diabetes ◽  
1992 ◽  
Vol 41 (4) ◽  
pp. 515-520 ◽  
Author(s):  
D. O. Sobel ◽  
J. Newsome ◽  
C. H. Ewel ◽  
J. A. Bellanti ◽  
V. Abbassi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Poly I:C ◽  
Bb Rat

Poly I:C induces development of diabetes mellitus in BB rat

Diabetes ◽  
1992 ◽  
Vol 41 (4) ◽  
pp. 515-520 ◽  
Author(s):  
D. O. Sobel ◽  
J. Newsome ◽  
C. H. Ewel ◽  
J. A. Bellanti ◽  
V. Abbassi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Poly I:C ◽  
Bb Rat

scholarly journals High Dose Vardenafil Blunts the Hypertensive Effects of Toll-Like Receptor 3 Activation During Pregnancy

2021 ◽  
Vol 1 ◽  
Author(s):  
Dakshnapriya Balasubbramanian ◽  
Sathish Dharani ◽  
Mohammad Tauseef ◽  
Mansoor A. Khan ◽  
Ziyaur Rahman ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Immune System ◽  
Innate Immune System ◽  
Low Dose ◽  
Innate Immune ◽  
Poly I:C ◽  
High Dose ◽  
Fetal Demise ◽  
Immune System Activation ◽  
Similar Drug

The maternal innate immune system plays a central role in preeclampsia (PE). Toll-like receptors (TLRs) are innate immune system receptors that recognize characteristics of extracellular endogenous ligands or pathogens, and their activation leads to a pro-inflammatory immune response. We and others have reported that excessive activation of TLRs causes pregnancy-dependent hypertension in animals and is associated with PE in women. Activation of TLR3 by poly I:C mimics the innate immune system activation by viruses that women who develop PE encounter during pregnancy. Vardenafil was approved by the FDA for erectile dysfunction but has recently been examined as a potential PE medication due to studies done with a similar drug, sildenafil. Preclinical as well as recent clinical studies demonstrate the potential effectiveness of sildenafil for PE. However, vardenafil is more potent than sildenafil and acts by increasing expression of placental growth factor in addition to increasing cGMP levels. We hypothesized that vardenafil will be more potent and effective in reducing the negative health effects in a mouse model of virus-induced PE. Pregnant mice were injected with the TLR3 agonist poly I:C (PPIC) on gestational days 13, 15, and 17. We treated PPIC mice with a high dose of vardenafil (50 mg human equivalent), a lower dose of vardenafil (20 mg human equivalent), or sildenafil (50 mg human equivalent) on gestational days 15–17 after hypertension was established. Daily i.p. injections of either high dose or low dose vardenafil significantly decreased systolic blood pressure in PPIC mice whereas sildenafil had no effect. There were no differences in body weight between the groups. The splenomegaly induced in PPIC mice was ameliorated in high dose vardenafil-treated PPIC mice, while low dose vardenafil-treated and sildenafil-treated PPIC mice still exhibited splenomegaly. High dose vardenafil-treated PPIC mice also did not exhibit any fetal demise characteristic of PPIC mice, while low dose vardenafil-treated and sildenafil-treated PPIC mice still had significantly increased incidences of fetal demise. These data support the notion that high dose vardenafil may be safe and effective at reducing blood pressure during a virus-associated hypertensive pregnancy.

Ovarian Dysfunction in Fetally Irradiated Beagles

1977 ◽  
Vol 35 ◽  
pp. 658-659
Author(s):  
T. M. Seed ◽  
M. H. Sanderson ◽  
D. L. Gutzeit ◽  
T. E. Fritz ◽  
D. V. Tolle ◽  
...  
Keyword(s):  
Gamma Rays ◽  
Low Dose ◽  
Long Term Effects ◽  
Ovarian Dysfunction ◽  
Dose Rates ◽  
Highly Sensitive ◽  
Microscopic Evaluation ◽  
Ovarian Pathology ◽  
Normal Offspring

The developing mammalian fetus is thought to be highly sensitive to ionizing radiation. However, dose, dose-rate relationships are not well established, especially the long term effects of protracted, low-dose exposure. A previous report (1) has indicated that bred beagle bitches exposed to daily doses of 5 to 35 R 60Co gamma rays throughout gestation can produce viable, seemingly normal offspring. Puppies irradiated in utero are distinguishable from controls only by their smaller size, dental abnormalities, and, in adulthood, by their inability to bear young.We report here our preliminary microscopic evaluation of ovarian pathology in young pups continuously irradiated throughout gestation at daily (22 h/day) dose rates of either 0.4, 1.0, 2.5, or 5.0 R/day of gamma rays from an attenuated 60Co source. Pups from non-irradiated bitches served as controls. Experimental animals were evaluated clinically and hematologically (control + 5.0 R/day pups) at regular intervals.

High Resolution Microscopy of Multi-Layered Biological Crystals

1982 ◽  
Vol 40 ◽  
pp. 80-83
Author(s):  
H.A. Cohen ◽  
T.W. Jeng ◽  
W. Chiu
Keyword(s):  
High Resolution ◽  
Low Dose ◽  
Three Dimensional ◽  
Data Interpretation ◽  
Two Dimensional ◽  
Biological Objects ◽  
Density Maps ◽  
Density Map ◽  
Complex Crystal ◽  
High Resolution Microscopy

This tutorial will discuss the methodology of low dose electron diffraction and imaging of crystalline biological objects, the problems of data interpretation for two-dimensional projected density maps of glucose embedded protein crystals, the factors to be considered in combining tilt data from three-dimensional crystals, and finally, the prospects of achieving a high resolution three-dimensional density map of a biological crystal. This methodology will be illustrated using two proteins under investigation in our laboratory, the T4 DNA helix destabilizing protein gp32*I and the crotoxin complex crystal.

Sign in / Sign up

Export Citation Format

Share Document