Plaque activation

None of the current imaging techniques (typically monitoring luminal diameter, volume, and thickness of the plaque, etc.) is capable of characterizing biological plaque activity to identify high-risk patients. Therefore, a considerable research effort concentrated in the development of... 

The concentration of t-PA in human blood is 2—5 ng/mL, ie, 2—5 ppb. Plasminogen activation is accelerated in the presence of a clot, but the rate is slow. The dissolution of a clot requites a week or more during normal repair of vascular damage (17). Prevention of irreversible tissue damage during a heart attack requires that a clot, formed by mpture of an atherosclerotic plaque, be dissolved in a matter of hours. This rapid thrombolysis (dissolution of the clot) must be achieved without significant tibrinogenolysis elsewhere in the patient. 

In the treatment of diseases where the metaboUtes are not being deUvered to the system, synthetic metaboUtes or active analogues have been successfully adrninistered. Vitamin metaboUtes have been successfully used for treatment of milk fever ia catde, turkey leg weakness, plaque psoriasis, and osteoporosis and renal osteodystrophy ia humans. Many of these clinical studies are outlined ia References 6, 16, 40, 51, and 141. The vitamin D receptor complex is a member of the gene superfamily of transcriptional activators, and 1,25 dihydroxy vitamin D is thus supportive of selective cell differentiation. In addition to mineral homeostasis mediated ia the iatestiae, kidney, and bone, the metaboUte acts on the immune system, P-ceUs of the pancreas (iasulin secretion), cerebellum, and hypothalamus. 

Sintering is a thermal process through which a loose mass of particles is transformed to a coherent body. It usually takes place at a temperature equal to two-thirds the melting point, or ca 800—1000°C for nickel. The sintered nickel stmcture without active material is called a plaque and it can be prepared by either dry or wet processes (see Metallurgy, powder). 

Usually the plaques produced by either method are coined (compressed) in those areas where subsequent welded tabs are coimected or where no active material is desired, eg, at the edges. The uncoined areas usually have a Bmnauer-Emmet-TeUer (BET) area in the range of 0.25—0.5 m /g and a pore volume >80%. The pores of the sintered plaque must be of suitable size and intercoimected. The mean pore diameter for good electrochemical efficiency is 6—12 p.m, deterrnined by the mercury-intmsion method. 

The process by which porous sintered plaques are filled with active material is called impregnation. The plaques are submerged in an aqueous solution, which is sometimes a hot melt in a compound s own water of hydration, consisting of a suitable nickel or cadmium salt and subjected to a chemical, electrochemical, or thermal process to precipitate nickel hydroxide or cadmium hydroxide. The electrochemical (46) and general (47) methods of impregnating nickel plaques have been reviewed. 

In the original process for the positive electrode, the plaques were placed in a metal vessel, which was evacuated to <5.3 kPa (40 mm Hg), and a nearly saturated solution of nickel nitrate (density 1.6 g/mL) admitted. After a 5—15 min soaking period, the plaques were transferred at 101 kPa (1 atm) to a polarizing unit where they were cathodicaHy polarized in hot caustic solution. After polarization the plates were washed and dried. These four steps were repeated four or five times until the desired weight gain of active material was achieved. 

In most cases, the impregnation process is followed by an electrochemical formation where the plaques are assembled into large temporary cells filled with 20—30% sodium hydroxide solution, subjected to 1—3 charge—discharge cycles, and subsequentiy washed and dried. This eliminates nitrates and poorly adherent particles. It also increases the effective surface area of the active materials. 

Active agents vary according to use. For controlling bad breath, 2iac salts, sodium lauryl sulfate, and flavors are used. To destroy oral microorganisms, chlorhexidine, cetylpyridinium chloride [123-03-5] and ben2alkonium chloride [68391-01-5] are valuable. Essential oils, such as thymol [89-83-8] eucalyptol [470-82-6] menthol, and methyl salicylate [119-36-8] reduce plaque-related gingivitis (see Oils, essential). Sodium fluoride aids ia caries coatrol. 

Xia M, Qin S, McNamara M, Mackay C, Hyman BT (1997) lnterleukin-8 receptor B immunore-activity in brain and neuritic plaques of Alzheimer s disease. Am J Pathol 150 1267-1274 Xia MQ, Bacskai BJ, Knowles RB, Qin SX, Hyman BT (2000) Expression of the chemokine receptor CXCR3 on neurons and the elevated expression of its ligand IP-10 in reactive astrocytes in vitro ERKl/2 activation and role in Alzheimer s disease. J Neuroimmunol 108 227-235 Xia MQ, Qin SX, Wu LJ, Mackay CR, Hyman BT (1998) Immunohistochemical study of the beta-chemokine receptors CCR3 and CCR5 and their Ugands in normal and Alzheimer s disease brains. Am J Pathol 153 31-37... 

Fig. 11.7 A, diagrammatic representation of plaque assay for evaluating virucidal activity and B, monolayers of baby hamster ki(hiey (BHK) cells C, virus tte untreated virus (o represents a plaque-forming unit, pfu, in BHK cells) D, virus titre disinfectant-treated virus (before plating onto BHK, die disinfectant must be neuh alized in an appropriate manner). Note the greatly reduced nimiber of pfu in D, indicative of fewer iminactivated virus particles than in C. 

At cellular level each stage of atheroma development is accompanied by the expression of specific glycoproteins by endothelial cells which mediate the adhesion of monocytes and T-lymphocytes. Their recruitment and migration is triggered by various cytokines released by leukocytes and possibly by smooth muscle cells. Atheroma development continues with the activation of macrophages, which accumulate lipids and become, together with lymphocytes, so-called fatty streaks. The continuous influx, differentiation and proliferation finally leads to more advanced lesion and to the formation of the fibrous plaque. ... 

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