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USE OF TUMOR NECROSIS FACTOR-alpha RECEPTOR p75 FOR TREATMENT OF ISCHEMIA-INDUCED NEOVASCULARIZATION

a tumor necrosis factor and tumor necrosis technology, applied in the direction of automatic disconnection emergency protective arrangements, peptide/protein ingredients, depsipeptides, etc., can solve the problem of increasing the risk of atherosclerosis of the coronary and peripheral arteries, and achieve the effect of reducing, suppressing, attenuating, diminishing, or stabilizing the development or progression of disease or disorder an organism

Inactive Publication Date: 2012-01-19
STEWARD RES & SPECIALTY PROJECTS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0037]By “operably linked” is meant that the polynucleotide of the invention (e.g., a DNA molecule) is positioned adjacent to a DNA sequence that directs transcription and translation of the sequence (i.e., facilitates the production of, for example, a recombinant polypeptide of the invention, or an RNA molecule).
[0042]“Therapeutic compound” means a substance that has the potential of affecting the function of an organism. A therapeutic compound may decrease, suppress, attenuate, diminish, arrest, or stabilize the development or progression of disease or disorder an organism.

Problems solved by technology

Aging is associated with an increased risk of atherosclerotic disease of the coronary and peripheral arteries.

Method used

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  • USE OF TUMOR NECROSIS FACTOR-alpha RECEPTOR p75 FOR TREATMENT OF ISCHEMIA-INDUCED NEOVASCULARIZATION
  • USE OF TUMOR NECROSIS FACTOR-alpha RECEPTOR p75 FOR TREATMENT OF ISCHEMIA-INDUCED NEOVASCULARIZATION
  • USE OF TUMOR NECROSIS FACTOR-alpha RECEPTOR p75 FOR TREATMENT OF ISCHEMIA-INDUCED NEOVASCULARIZATION

Examples

Experimental program
Comparison scheme
Effect test

example 1

Neovascularization and EPC Mobilization is Mediated by p75 TNFR2 Signaling

[0122]To evaluate the effect of bone marrow transplantation on neovascularization in old mice and to examine the role of functional p75 receptor / TNFR2 in post-ischemic recovery, two bone marrow transplantation murine models were established. The first model was used to evaluate whether the replacement of old p75KO bone marrow with young wild-type marrow would prevent limb autoamputation in old p75KO mice. This model provides for the evaluation of the contribution of wild-type bone marrow-derived cells to the processes of post-ischemic recovery in p75KO tissue. To evaluate the contribution of bone marrow-derived p75KO cells to post-ischemic recovery in otherwise wild-type tissue, a second murine model was established. In this model, old wild type mice were treated with lethal irradiation to destroy their endogenous bone marrow and the old wild-type mice were subsequently transplanted with bone marrow from young...

example 2

Ischemia-Induced Angiogenesis is Impaired in Old TNFR2 KO Mice

[0123]When assessing the relationship between age and TNFR1 and 2 levels in EPCs, a 25-30% statistically non-significant decrease in p55 levels was found in EPCs from elderly mice compared with younger animals. In contrast, there was a more than 55% (P<0.01) decrease in p75 mRNA levels in EPCs from elderly mice compared with younger animals.

[0124]Mean blood flow in young wild-type mice twenty-eight days after hind limb surgery reached 80% of the pre-ischemic flow (FIG. 1A, black bars). In contrast, recovery of blood flow was delayed up to fourteen days in old wild-type (gray bars) and young p75KO (clear bars) mice (40% of pre-ischemic value vs. 80% in young wild-type mice, P<0.03), but was similar to the recovery in young wild-type mice thereafter (FIG. 1A, days 21 and 28). These results suggested that old wild-type and young p75KO mice exhibit a partial and temporal insufficiency of post-ischemic recovery compared with ...

example 3

Ischemia-Induced VEGF Expression is Lower in the Limbs of p75KO Mice

[0129]When VEGF expression in the muscles of operated limbs was assessed by immunofluorescence, it was highly expressed in the muscle tissue of wild-type mice between days 3 and 7 post-surgery (FIG. 2A, upper panel). In contrast, VEGF expression was minimal in the tissues of p75KO mice between days 3 and 7 (FIG. 2A, lower panel), suggesting that ischemia-induced VEGF expression is impaired in p75KO mice.

[0130]Densitometric analysis of total RNA from hind limb muscle revealed that VEGF expression was not detectable in p75KO mice 3 days after hind limb surgery (FIG. 2B, upper panel), whereas VEGF was highly expressed in wild-type tissue (FIG. 2B, upper panel, clear bars), confirming the immunofluorescent staining results (FIG. 2A). By day 10 VEGF was also detectable in p75KO mice (FIG. 2B, upper panel, black bars), but was about half the level of wild-type controls.

[0131]These results differed from those obtained whe...

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Abstract

Improvements on the basic method used for BEAMing increase sensitivity and increase the signal-to-noise ratio. The improvements have permitted the determination of intrinsic error rates of various DNA polymerases and have permitted the detection of rare and subtle mutations in DNA isolated from plasma of cancer patients.

Description

BACKGROUND OF THE INVENTION[0001]Aging is associated with an increased risk of atherosclerotic disease of the coronary and peripheral arteries. In either vascular system, the extent of ischemic damage and degree of subsequent functional recovery after arterial obliteration largely depends on the development of new collateral blood vessels. Aging is associated with impaired angiogenesis in murine and rabbit limb ischemia models. Aging is also accompanied by a steady decline in immune functions, such as defects in signaling pathways and altered expression of cytokines, such as interferon-gamma (IFNγ) and vascular endothelial growth factor (VEGF). Angiogenesis is associated with perivascular inflammation and monocyte / macrophage accumulation.[0002]Tumor necrosis factor alpha (TNF-α), a macrophage / monocyte-derived pluripotent mediator, can function as an angiogenic factor in one system and as an anti-angiogenic factor in another. These mutually exclusive effects have been attributed to T...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K49/00C12N15/85A61K38/18A61K38/19A61P9/10A61K38/44C12N15/63C12N5/10G01N33/566C12Q1/68A61K48/00A61K38/30
CPCC12Q1/6858C12Q2565/537C12Q2563/155C12Q2527/125G01R31/3277H02H1/0015H02H3/33G01R31/52A61P9/10
Inventor LOSORDO, DOUGLAS W.GOUKASSIAN, DAVID A.
Owner STEWARD RES & SPECIALTY PROJECTS
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