Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The average daily consumption of seal oil by the Inuit people is approximately 8-9 g, yet there is very little information on the effect of seal oil consumption on cardiovascular disease risk factors. In this study, 19 healthy, normocholesterolemic subjects consumed 20 g of encapsulated seal oil containing eicosapentaenoic acid (EPA; 20:5n-3), docosahexaenoic acid (DHA; 22:6n-3), and docosapentaenoic acid (DPA; 22:5n-3) or 20 g of vegetable oil (control) per day for 42 days. Levels of selected cardiovascular and thrombotic risk factors as well as fatty acid profiles of serum phospholipid and nonesterified fatty acid (NEFA) were determined. EPA levels in serum phospholipid and NEFA increased by 4.3- and 2.7-fold, respectively, in the seal oil supplemented group. DHA levels rose 1.5- and 2.1-fold, respectively, and DPA levels rose 0.5- and 0.7-fold, respectively. Arachidonic acid (AA) levels dropped by 26% in both serum phospholipid and serum NEFA. There was a significant decrease in the ratio of n-6 to n-3 fatty acids in serum phospholipid from 7.2 to 2.1 and a significant increase in the ratio of EPA/AA in NEFA. Ingestion of seal oil raised the coagulant inhibitor, protein C, values by 7% and decreased plasma fibrinogen by 18%. No alterations in other hemostatic variables, including plasma activity of Factors VII, VIII, IX, and X and antithrombin, or in the concentrations of von Willebrand Factor, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, glucose, Apo A-1, or lipoprotein(a) were observed in either group. Other risk factors for cardiovascular disease, including hematocrit, white blood cell count, plasma viscosity, systolic and diastolic blood pressures, heart rate, and platelet aggregation after stimulation with ADP or collagen did not change. Our results indicate that seal oil supplementation in healthy, normocholesterolemic subjects decreased the n-6/n-3 ratio and increased EPA, DHA, and DPA and the ratio of EPA/AA and DHA/AA in the serum phospholipid and NEFA, while exhibiting a modest beneficial effect on fibrinogen and protein C levels.
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PMID:Effect of supplementation with dietary seal oil on selected cardiovascular risk factors and hemostatic variables in healthy male subjects. 1058 67

Some drugs have the undesired side effect of systemically stimulating the immune system, which may eventually lead to the development of drug-induced allergy or autoimmunity. Unfortunately, validated predictive screening tools to assess the immune stimulatory potential of compounds are presently unavailable. The popliteal lymph node assay (PLNA) with reporter antigens (RA) seems a valuable candidate for this purpose. The aims of the present study were 1) to provide additional mechanistic information on the very early induction phase of drug-induced type 1 (T(H)1-associated) and type 2 (T(H)2-associated) immune reactions in the PLNA and 2) to explore the use of these mechanism-based parameters to predict the immune stimulating potential of drugs. Streptozotocin (STZ), a chemotherapeutic drug, and D-Penicillamine (D-Pen, anti-rheumatic drug) were used as model compounds as they respectively induce clearly differentiated type 1 and type 2 immune responses in the PLNA. Type 1 responses were characterized by the production of high levels of IFNgamma and IL-12 from day 2 after exposure. Expression of CD40 was absent, but CD54, CD80, and CD86 were present predominantly on non-B APC, presumably macrophages. Increased percentages of activated CD8(+) T-cells and macrophages accompanied these phenomena. Type 2 responses were clearly different and were characterized by an early influx of dendritic cells (DC) and B-cells that expressed CD40, CD54, and CD86, but no CD80. First DC, but later B-cells, appeared to function as APC. In addition, the production of IL-4 was elevated. Apparently, reactivity of these type 1- and type 2-inducing drugs produce drug-specific patterns of immune stimulating factors that determine very different, time-dependent profiles of activated cells, cytokine production, and expression of co-stimulatory molecules very shortly after the initial exposure to drugs. As such, these parameters obtained with the PLNA may help to provide information about the immunological mechanisms in the early induction phase of drug-induced immune stimulation and may be useful in the development of an appropriate screening test to predict the immune stimulatory potential of drugs in a preclinical phase.
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PMID:Drug-induced type 1 and type 2 immune responses are characterized by distinct profiles of cell kinetics, cytokine production, and expression of co-stimulatory molecules in the popliteal lymph node assay. 1895 67