Platelets human

Figure 11.4 PKG-dependent phosphorylation in intact human platelets. Human platelets were incubated in the presence of [ P]-orthophosphate and treated with buffer alone (control) or with 500 pM PKG activator 8pCPT-cGMP for 30 min (stimulation).

SAFETY PROFILE Poison by ingestion, subcutaneous, intraperitoneal, and intravenous routes. Human systemic effects by ingestion general anesthesia and thrombocytopenia (reduction in the number of blood platelets). Human effects on newborn by an unspecified route drug dependency and Apgar score (condition of newborn). Experimental teratogenic and reproductive effects. When heated to decomposition it emits toxic fumes of CL. 

Blood platelets Human Mg++ 0.0038 0.0024 Bettex-Galland and Liischer (1961)... 

Blood platelets Human Ca++ 0.0050 0.016 Bettex-Galland and Luscher (1961)... 

Rat brain Al Rat striatum A2a Human platelet PC 12 cell Rat atria A, Rat aorta A2a Rabbit platelet Human platelet ... 

Histamine is in mast cells, basophils, and platelets. Human skin mast cells express H H2, and H4 receptors, but not H3 receptors. Hi and H2 receptors are involved in wheal formation and erythema, whereas only Hi-receptor agonists cause pruritus. Complete blockade of Hi-receptors does not totally relieve itching, and combinations of Hi and H2 blockers may be superior to H, blockers alone. 

Rabbit alveolar Pig liver Rabbit alveolar Platelets, human Rat peritoneal... 

The formed elements consist primarily of red blood cells, ie, erythrocytes. Less than 1 /600 of the total volume of the formed elements is composed of white blood cells, ie, leukocytes, and less than 1/800 are platelets, ie, thrombocytes. Table 1 gives the typical constitution of human blood. 

Contamination of blood products with lymphocytes can lead to transfusion-induced reactions ranging from a mild fever to severe reactions such as alloimmunization and graft versus host disease (GvHD), in which the transfused lymphocytes (graft) survive the defensive immune reaction of the patient (host) and start a reaction which destroys the cells of the host. The patient also may develop an immune response to the human leukocyte antigen (HLA) type of the graft s cells and reject all platelet transfusions that do not match their own HLA system. The HLA system, found on blood platelets and lymphocytes, is more compHcated than, but similar to, the ABO blood group system of red cells. 

Transfusion-induced autoimmune disease has been a significant complication in the treatment of patients who require multiple platelet transfusions. Platelets and lymphocytes carry their own blood group system, ie, the human leukocyte antigen (HLA) system, and it can be difficult to find an HLA matched donor. A mismatched platelet transfusion does not induce immediate adverse reactions, but may cause the patient to become refractory to the HLA type of the transfused platelets. The next time platelets with an HLA type similar to that of the transfused platelets are transfused, they are rejected by the patient and thus have no clinical efficacy. Exposure to platelets originating from different donors is minimized by the use of apheresis platelets. One transfusable dose (unit) of apheresis platelets contains 3-5 x 10 platelets. An equal dose of platelets from whole blood donation requires platelets from six to eight units of whole blood. Furthermore, platelets can be donated every 10 days, versus 10 weeks for whole blood donations. 

Methylpyrazole has been investigated as a possible treatment for alcoholism. The stmcture—activity relationship (SAR) associated with a series of pyrazoles has been examined ia a 1992 study (51). These compounds were designed as nonprostanoid prostacyclin mimetics to inhibit human platelet aggregation. In this study, 3,4,5-triphenylpyrazole was linked to a number of alkanoic acids, esters, and amides. From the many compounds synthesized, triphenyl-IJT-pyrazole-l-nonanoic acid (80) was found to be the most efficacious candidate (IC g = 0.4 //M). 

Factor V. High in sialic acid content. Factor V is a large asymmetric single-chain glycoprotein that becomes an active participant in the coagulation cascade when it is converted to its active form by a-thrombin. Approximately 25% of human Factor V is found in the whole blood associated with platelets. Factor V is an essential cofactor along with Factor Xa plus phosphohpid plus Ca " in the conversion of prothrombin to thrombin. 

Components/ mechanism of action Human plasma, fibrinogen and thrombin, virally inactivated, hemostat, sealant. Autologous fibrinogen -t-platelet-rich plasma, hemostatic gel. Bovine collagen, bovine thrombin, plus autologous human plasma, hemostatic agent. Bovine collagen and bovine thrombin. Expands 20% which aids in hemostatic effect. 

Compound D is an effective inhibitor of TXA2 biosynthesis in human blood platelets at the micromolar level. 

It was discovered that 3-iiitro-2-piperidiiio-, 3-iiitro-7-piperidiiio-, and 7-A -diethaiiolamiiio-3-iiitro-l, 8-iiaphthyridiii-2(lH)-oiies and 2-diethanol-amino-7-piperidino-3-nitro-l,8-naphthyridine showed remarkable aetivity to inhibit human platelet aggregation in vitro indueed by araehidonie aeid, eollagen, and ADR Tliis aetivity was eomparable to papaverine, dipyridamole, and ibuprofen (94EJMC735). 

Direct laser-assisted myocardial revascularization (DMR) is an approved technique in the US, Europe, and parts of Asia to create numerous myocardial channels. This results in the induction of a massive inflammatory reaction, which in turn induces angiogenesis. The other FDA-approved pro-angiogenic therapy is the use of recombinant human platelet-derived growth factor (Regranex) for use in the treatment of diabetic neuropathic foot ulcer s. 

COX-2 synthesises PGI2 (prostacyclin) and the high incidence of myocardial infarctions with selective COX-2 inhibitors has been attributed to inhibition of COX-2 in vascular tissues. Prostacyclin, made by blood vessel walls, inhibits aggregation of platelets and maintains a balance with thromboxane. Thromboxane, which is released by platelets, promotes clotting. Prostacyclin is synthesised mostly by COX-1, but in humans selective COX-2 inhibition reduces its biosynthesis in vivo. This reduced synthesis may lead to an overactive thromboxane system and increased risk of thromboembolism. 

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