Rdnaderived Miscellaneous Products

Antihemophilic Factor. Antihemophilic factor (factor VIII) (Humate-P, Hemophil M, Koate HP, Monoclate-P) is a glycoprotein found in human plasma and a necessary cofactor in the blood-clotting mechanism. This high-molecular-weight glycoprotein has a complex structure with several components (subcofactors).95 The commercially available concentrates derived from blood collected from volunteer donors by the American Red Cross Blood Services are used primarily for the treatment of patients with hemophilia A. Because the commercially available products are purified concentrates derived from blood pooled from millions of donors, the major precautions in using the products relate to transmission of viruses, such as hepatitis virus, herpesvirus, and HIV. This major problem has been alleviated, mostly because of the development and marketing of rDNA-derived antihemophilic factors.

Antihemophilic Factor (Recombinant). Antihemophilic factor (recombinant), rAHF (KoGENate, Helixate), is an rDNA-derived factor VIII expressed in genetically engineered baby hamster kidney cells.96 KoGENate has the same biological activity as the human plasma-derived antihemophilic factor (pdAHF). The purification process for rAHF includes monoclonal antibody immunoaffinity chromatography to remove any protein contaminants.

rAHF is indicated for the treatment of hemophilia A and is administered by the intravenous route. Patients suffering from hemophilia A exhibit a decrease in the activity of plasma clotting factor VIII. This product temporarily prevents bleeding episodes in hemophiliacs and may be used to prevent excessive bleeding during surgical procedures in these patients. A major advantage of the rAHF over the natural factor VIII is the lack of virus in the product. rAHF does not contain von Willebrand factor; therefore, it is not indicated in the treatment of von Willebrand disease. Patients receiving rAHF should be monitored carefully for the development of antibodies.

Bioclate is an rDNA-derived factor VIII expressed in genetically engineered Chinese hamster ovary cells. It has the same biological activity as pdAHF and is structurally similar. Its indications and adverse effects are similar to those for KoGENate.

# REVIEW QUESTIONS#

1. The rennin-angiotensin system plays an important role in regulation of blood pressure. As such, this pathway encompasses the conversion of an approximately 400-amino acid sequence to a decapeptide, then to the biologically active octapeptide and is an excellent target for drug therapy to manage hypertension. Describe the starting protein and its conversion to the biologically active metabolite. Be sure to include the enzymes involved in the conversion of the protein and peptides.

2. In the digestion and absorption of dietary protein:

a. pepsinogen is converted to pepsin by gastrin via a pro-teolysis reaction.

b. chymotrypsinogen is activated by trypsin.

c. carboxypeptidase activates pepsinogen in the stomach.

d. hydrochloric acid activates aminopeptidase.

3. Clinically, which of the following is used to dissolve necrotic tissue of second- and third-degree burn patients?

a. streptokinase b. sutilains c. trypsin d. dornase e. lypressin

4. While working in your basement you discover a method of producing proteins and peptides that has never been described in the literature. What is the significance of being able to produce cytokines such as interferons?

5. You have discovered a protein that is capable of blocking the progression of Alzheimer disease. The sources of this protein are very limited, and you need additional material to complete a phase II clinical trial. Describe how you would use rDNA technology to produce more of this wonder drug.

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Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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