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The second type of granule is the granule discount vardenafil 10 mg without a prescription, which contains a heparin antagonist (heparin interferes with blood clotting purchase vardenafil 10 mg fast delivery; see biochemical com- Idiopathic thrombocytopenic pur- ments), platelet-derived growth factor, -thromboglobulin, fibrinogen, von Wille- pura (ITP) is an autoimmune dis- brand factor (vWF), and other clotting factors. The third type of granule is the lyso- ease in which antibodies to platelet somal granule, which contains hydrolytic enzymes. During activation, the contents glycoproteins are produced. Antibody bind- of these granules, which modulate platelet aggregation and clotting, are secreted. PLATELET ACTIVATION is the appearance of small red spots on the skin (petechial hemorrhages) caused by Three fundamental mechanisms are involved in platelet function during blood coag- blood leakage from capillaries. Minor dam- ulation: adhesion, aggregation, and secretion. Adhesion sets off a series of reactions age to vascular endothelial cells is constantly termed platelet activation, which leads to platelet aggregation and secretion of being caused by mechanical forces related to platelet granule contents. In patients with ITP, few platelets The adhesion step refers primarily to the platelet–subendothelial interaction that are available to repair the damage. Blood vessel injury exposes collagen, subendothelial matrix-bound vWF, and other matrix components. The platelet cell membrane contains glycoproteins (GPs) that bind to collagen and to vWF, causing the platelet Von Willebrand factor is a large multimeric glycoprotein with a GPIb GPIIb GPIIIa GPIa subunit molecular weight of 220,000 daltons. Its size in the circulation Platelet ranges between 500 and 20,000 kDa, and its membrane role in circulation is to stabilize Factor VIII and protect it from degradation. The high- 2 3 1 molecular-weight forms are concentrated in Adhesion VWF Exposed by Adhesion the endothelium of blood vessels and are initial adhesion released in response to stress hormones and events endothelial damage. High-molecular-weight Subendothelial vWF released by the endothelium is cleaved collagen by a specific metalloprotease in the serum, reducing the size of the circulating vWF. Adhesion of platelets to the subendothelial cell layer.

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After bacterial colonies or bands of DNA are transferred to nitrocellulose paper buy vardenafil 10 mg visa, the paper is treated with an alkaline solution generic vardenafil 10 mg otc. Alkaline solutions denature DNA (that is, separate the two strands of each Press nitrocellulose paper onto double helix). The single-stranded DNA is then hybridized with a probe, and the the plate regions on the nitrocellulose blot containing DNA that base-pairs with the probe are Orientation Cells from each colony adhere to the paper identified. Southern developed the technique, which bears his name, for identifying DNA sequences on gels. Southern blots are produced when DNA on a nitrocellu- Nitrocellulose paper lose blot of an electrophoretic gel is hybridized with a DNA probe. Molecular biol- containing bacterial ogists decided to continue with this geographic theme as they named two additional cells techniques. Northern blots are produced when RNA on a nitrocellulose blot is hybridized with a DNA probe. A slightly different but related technique, known as a Western blot, involves separating proteins by gel electrophoresis and probing with Treat with alkali to disrupt cells labeled antibodies for specific proteins (Fig. DNA SEQUENCING Add radioactive DNA probe for specific DNA sequences The most common procedure for determining the sequence of nucleotides in a DNA Incubate, then wash to remove strand was developed by Frederick Sanger and involves the use of dideoxynu- probe that has not hybridized cleotides. Dideoxynucleotides lack a 3 -hydroxyl group (in addition to lacking the 2 hydroxyl group normally absent from DNA deoxynucleotides). Thus, once they are incorporated into the growing chain, the next nucleotide cannot add, and poly- Probe hybridized merization is terminated. In this procedure, only one of the four dideoxynucleotides to DNA (ddATP, ddTTP, ddGTP, or ddCTP) is added to a tube containing all four normal deoxynucleotides, DNA polymerase, a primer, and the template strand for the DNA that is being sequenced (Fig. As DNA polymerase catalyzes the sequential addition of complementary bases to the 3’ end, the dideoxynubleotide competes with its corresponding normal nucleotide for insertion. Whenever the dideoxynu- Perform autoradiography cleotide is incorporated, further polymerization of the strand cannot occur, and syn- thesis is terminated. Some of the chains will terminate at each of the locations in the template strand that is complementary to the dideoxnucleotide.

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They are found in the skin order 10mg vardenafil otc, muscles cheap 10 mg vardenafil fast delivery, and joints Figure 11-19 Sensory receptors in the skin. One is for acute, sharp pain, Sense of Temperature and the other is for slow, chronic pain. Thus, a single strong stimulus produces the immediate sharp pain, followed in a The temperature receptors are free nerve endings, receptors second or so by the slow, diffuse, burning pain that in- that are not enclosed in capsules, but are merely branchings creases in severity with the passage of time. Temperature receptors are widely distributed vides information on referred pain. A warm object stimulates only the heat receptors, and quickly, and occasionally it cannot be remedied at all. Internally, there the latter case, it is desirable to lessen the pain as much as are temperature receptors in the hypothalamus of the brain, possible. Some pain relief methods that have been found which help to adjust body temperature according to the tem- to be effective include: perature of the circulating blood. An analgesic (an-al-JE-zik) is a drug Sense of Position that relieves pain. There are two main categories of Receptors located in muscles, tendons, and joints relay im- such agents: pulses that aid in judging one’s position and changes in the ◗ Nonnarcotic analgesics act locally to reduce inflam- locations of body parts in relation to each other. They also mation and are effective for mild to moderate pain. These rather widespread receptors, known steroidal antiinflammatory drugs (NSAIDs). Exam- as proprioceptors (pro-pre-o-SEP-tors), are aided in this ples are ibuprofen (i-bu-PRO-fen) and naproxen (na- function by the equilibrium receptors of the internal ear. Information received by these receptors is needed for ◗ Narcotics act on the CNS to alter the perception and the coordination of muscles and is important in such ac- response to pain.

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