296084 pdf eng

Rudiger Overmans used the description "Poland" to summarize the figures for the region east of the Oder—Neisse linewhich included the Former eastern territories of GermanyDanzigpre war Poland, and the Memel Territory [5] The population surveyed in pre war Poland included Polish citizens on the Volksliste who were of dubious German ancestry. Confirmed deaths in Poland include 17, refugees in Denmark and about 15, in Polish internment camps.

296084 pdf eng

More specifically, the invention is related to pharmaceutical 296084 pdf eng comprising such LNA compounds and the use of these compounds and compositions in the prevention or treatment of such diseases.

G-CSF has been indicated in chronic inflammatory autoimmune diseases, such as type II hypersensitivity responses, including rheumatoid arthritis. G-CSF protein has been developed as a therapeutic agent for increasing white blood cell counts, and can enhance the immune system's ability to raise a Th-2 response that can decrease Th-1 mediated inflammatory responses, for example in Crohn's disease.

It is a glycoprotein, growth factor or cytokine produced by a number of different tissues to stimulate the bone marrow to produce granulocytes and stem cells. G-CSF then stimulates the bone marrow to release them into the blood. It also stimulates the survival, proliferation, differentiation, and function of neutrophil precursors and mature neutrophils.

It is playing importance in inflammatory joint diseases as G-CSF-deficient mice are protected from acute and chronic arthritis. Reduced severity was associated with blunted mobilization of granulocytic cells from the bone marrow and less cellular infiltrate and cellular activation in inflamed joints.

It has also been demonstrated that G-CSF blockade in established collagen-induced arthritis in WT mice markedly reduces disease manifestations and is as effective as tumor necrosis factor blockade. G-CSF plays a critical role in driving joint inflammation and G-CSF is a potential therapeutic target in inflammatory joint diseases, such as rheumatoid arthritis Lawlor et al.

M-CSF Macrophage colony-stimulating factor, or M-CSF, is a secreted cytokine which influences hemopoietic stem cells to differentiate into macrophages or 296084 pdf eng related cell types. Osteoclasts mediate bone readsorption.

Osteoclasts are multinucleated cells differentiating from haemopoietic cells Walker, Science The differentiation of osteoclast precursors into mature multinucleated osteoclasts requires different factors including hormonal and local stimuli Walker, Science Osteoblastic or bone marrow stromal cells are also required for osteoclast differentiation and one of the factors produced by these cells that supports osteoclast formation is macrophage-colony stimulating factor, M-CSF Yoshida et al.

Thus, there remains a need in the art to identify new agents and methods for preventing or treating osteolysis or cancer metastasis, including osteolytic bone metastases. M-CSF plays a more general role in formation of cancer metastasis. M-CSF regulates these processes through the recruitment and regulation of macrophages, cells that become associated with mammary tumors and the terminal end buds at the end of the growing ducts.

This phenomenon suggests that the tumors subvert normal developmental processes to allow invasion into the surrounding stroma, a process that gives the tumor access to the vasculature and consequently the promotion of metastasis.

In addition, soluble M-CSF secreted from the tumor acts to divert antitumor macrophage responses and suppresses the differentiation of mature tumor-antigen-presenting dendritic cell Lin et al. Monocyte Chemoattractant Protein-1 MCP-1 The chemoattractant cytokines, termed as chemokines, are a large family of low molecular weight proteins that share the ability to stimulate directed cell migration [Schall, Cytokine 3: Chemokines have been implicated as important mediators of allergic, inflammatory and autoimmune disorders and diseases, such as asthma, atherosclerosis, glomerulonephritis, pancreatitis, restenosis, rheumatoid arthritis, diabetic nephropathy, pulmonary fibrosis, multiple sclerosis, and transplant rejection.

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Accordingly, the use of antagonists of chemokine function may help reverse or halt the progression of these disorders and diseases. With few exceptions, chemokines have four conserved cysteine residues that form disulfide bonds within the chemokine proteins. Two major chemokine subfamilies have been classified based on the chromosomal localization of the chemokine genes and the relative position of the first two cysteine residues Van Collie et al.

Monocyte chemoattractant protein-1 CCL-2 is a member of the C-C class of the beta chemokine family and one of the key factors involved in the initiation of inflammation. CCL-2 is typically secreted in the prevalent forms, 9 and 13 kDa, respectively, as a result of differential O-glycosylation.

296084 pdf eng

It triggers chemotaxis and transendothelial migration of monocytes to inflammatory lesions by interacting with the membrane CC chemokine receptor 2 CCR2 in monocytes O'Hayre et al. CCL-2 is secreted by fibroblasts, endothelial cells, vascular smooth muscle cells, monocytes, T cells, and other cell types that mediate the influx of cells to sites of inflammation Conti and DiGioacchino, CCL-2 expression has been observed in a large number of tissues during inflammation-dependent disease progression, including atherosclerosis Shin et al.

In these cases, the influx of macrophages into these tissues has been suggested to exacerbate the diseases. Thus, the expression of CCL-2, which is likely to be critical for fighting infectious disease, must be tightly regulated. Cytokine Growth Factor Rev 7: CCL-2 appears to play a significant role during the early stages of allergic responses because of its ability to induce mast cell activation and LTC4 release into the airway, which directly induces AHR airways hyper-responsiveness [Campbell et al.

CCL-2 has been found in the lungs of patients with idiopathic pulmonary fibrosis and is thought to be responsible for the influx of mononuclear phagocytes and the production of growth factors that stimulate mesenchymal cells and subsequent fibrosis [Antoniades et al.

In addition, CCL-2 is also involved in the accumulation of monocytes in pleural effusions implicated in both Mycobacterium tuberculosis infection and malignancy [Strieter et al.

CCL-2 has also been shown to be constitutively expressed by synovial fibroblasts from rheumatoid arthritis patients, and its levels are higher in rheumatoid arthritis joints compared to normal joints or those from other arthritic diseases [Koch et al.

These elevated levels of CCL-2 are probably responsible for the monocyte infiltration into the synovial tissue. CCL-2 also plays a critical role in the initiation and development of atherosclerotic lesions.

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CCL-2 is responsible for the recruitment of monocytes into atherosclerotic areas, as shown by immunohistochemistry of macrophage-rich arterial wall [Yla-Herttuala et al.

Other inflammatory diseases marked by specific site elevations of CCL-2 include multiple sclerosis MSglomerulonephritis, and stroke. Together, these findings infer CCL-2 as a therapeutic target in the treatment of inflammatory disease and strongly suggest that the discovery and development of novel compounds that block or down-regulate CCL-2 activity would be highly beneficial in treating inflammatory diseases.In the food and fresh meats industry, prices of domestic beef and imported beef were higher in comparison withthe corresponding period of the previous fiscal year.

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