Peripheral mechanism

Role of Growth Factors and Cytokines in These Pain Mechanisms (Peripheral). 

The principal organs involved in the peripheral clearance of hGH from the plasma are the kidney and fiver. hGH is cleared via glomerular filtration at the kidney and by a receptor-mediated mechanism at the fiver (58,59). In animal models, derivatives of hGH such as the 20,000 mol wt variant, oligomeric forms, and hGH complexed with GH-binding protein have been shown to be cleared from the semm at significandy lower rates than 22,000 mol wt hGH (60—62). The prolonged plasma half-life of these derivatives probably reflects a combination of decreased receptor affinity and size constraints on glomerular filtration. 

Laser ablation systems hold considerable promise if restenosis (reblocking of the arteries) rates are reduced. The rate as of 1995 is 30%, typically within six months. Mechanical or atherectomy devices to cut, shave, or pulverize plaque have been tested extensively in coronary arteries. Some of these have also been approved for peripheral use. The future of angioplasty, beyond the tremendous success of conventional balloon catheters, depends on approaches that can reduce restenosis rates. For example, if appHcation of a dmg to the lesion site turns out to be the solution to restenosis, balloon catheters would be used for both dilating the vessel and deUvering the dmg. An understanding of what happens to the arterial walls, at the cellular level, when these walls are subjected to the various types of angioplasty may need to come first. 

Pulpstones. Improvements have been made in the composition and speed of the grinding wheel, in methods of feeding the wood and pressing it against the stone, in control of power to the stones, and in the size and capacity of the units. The first pulpstones were manufactured from quarried sandstone, but have been replaced by carbide and alumina embedded in a softer ceramic matrix, in which the harder grit particles project from the surface of the wheel (see Abrasives). The abrasive segments ate made up of three basic manufactured abrasive siUcon carbide, aluminum oxide, or a modified aluminum oxide. Synthetic stones have the mechanical strength to operate at peripheral surface speeds of about 1200—1400 m /min (3900 to 4600 ft/min) under conditions that consume 0.37—3.7 MJ/s (500—5000 hp) pet stone. 

The traction thickener includes a traction mechanism where the movement of the rake is suppHed by a single long arm pivoted around the center column and driven by a troUey that moves on a peripheral rail around the basin. Such units have diameters of 60—130 m. 

Neuronal Norepinephrine Depleting Agents. Reserpine (Table 6) is the most active alkaloid derived from Rauwolfia serpentina. The principal antihypertensive mechanism of action primarily results from depletion of norepinephrine from peripheral sympathetic nerves and the brain adrenergic neurons. The result is a drastic decrease in the amount of norepinephrine released from these neurons, leading to decrease in vascular tone and lowering of blood pressure. Reserpine also depletes other transmitters including epinephrine, serotonin [50-67-9] dopamine [51-61-6] ... 

P-Adrenoceptor Blockers. There is no satisfactory mechanism to explain the antihypertensive activity of P-adrenoceptor blockers (see Table 1) in humans particularly after chronic treatment (228,231—233). Reductions in heart rate correlate well with decreases in blood pressure and this may be an important mechanism. Other proposed mechanisms include reduction in PRA, reduction in cardiac output, and a central action. However, pindolol produces an antihypertensive effect without lowering PRA. In long-term treatment, the cardiac output is restored despite the decrease in arterial blood pressure and total peripheral resistance. Atenolol (Table 1), which does not penetrate into the brain is an efficacious antihypertensive agent. In short-term treatment, the blood flow to most organs (except the brain) is reduced and the total peripheral resistance may increase. 

The principal mechanism of the hypotensive effect of diuretics (qv) is salt and fluid depletion, leading to reduction in blood volume (200,240). Acute effects lead to a decrease in cardiac output and an increase in total peripheral resistance. However, during chronic adrninistration, cardiac output and blood volume return toward normal and total peripheral resistance decreases to below pretreatment values. As a result, the blood pressure falls. The usual reduction in blood volume is about 5%. A certain degree of sustained blood volume contraction has to occur before the blood pressure decreases. The usual decrease in blood pressure achieved using a diuretic is about 20/10 mm Hg (2.7/1.3 kPa) (systoHc/diastoHc pressures. 

Oxolamine [959-14-8] (57) is sold in Europe. It is an oxadiazole, and its general pharmacological profile is described (81). The compound possesses analgesic, antiinflammatory, local anesthetic, and antispasmodic properties, in addition to its antitussive activity. Although a central mechanism may account for some of the activity, peripheral inhibition of the cough reflex may be the dominant effect. The compound has been shown to be clinically effective, although it is less active than codeine (82,83). The synthesis of oxolamine is described (84). 

Operating Costs Power cost for a continuous thickener is an almost insignificant item. For example, a unit thickener 60 m (200 ft) in diameter with a torque rating of 1.0 MN-m (8.8 Mlbf in) will normally require 12 kW (16 hp). The low power consumption is due to the very slow rotative speeds. Normally, a mechanism vi l be designed for a peripheral speed of about 9 m/min (0.5 ft/s), which corresponds to only 3 r/h for a 60-m (200-ft) unit. This low speed also means veiy low maintenance costs. Operating labor is low because little attention is normally required after initial operation has balanced the feed and underflow. If chemicals are required for flocculation, the chemical cost frequently dwarfs all other operating costs. 

Industrial process furnaces and ovens Mechanical powertransmission equipment, n.e.c. General industrial machinery and equipment, n.e.c. Electronic computers Computer storage devices Computer terminals Computer peripheral equipment, n.e.c. Calculating and accounting machines, except electronic computers Office machines, n.e.c. ... 

Mechanical means for controlled circulation of the solids slurry must be provided with at least a 3 1 range of speeds. The maximum peripheral speed of mixer blades should not exceed 6 ft/sec. 

Rotational speed of shaft and peripheral speeds of seal. Mechanical limitations—dimensions of space required versus space available, shaft deflection and whip, shaft end play, shaft diameter, and maintenance. Miscellaneous factors—cost, allowable by-pass or out-leakage, allowable contamination of gas with air, inert gas, oil, and other fluid. 

The maximum speed of a compressor is fixed by mechanical or structural limiting of the peripheral velocity of the impeller wheels. The required velocity is established by the head to be developed. The capacity of the machine at suction conditions is a function of the individual wheel designs and the diameter. ... 

Spur, external Connects parallel shafts that rotate in opposite directions, inexpensive to manufacture to close tolerances, moderate peripheral speeds, no axial thrust, high mechanical efficiency Noisy at high speeds... 

Although blood pressure control follows Ohm s law and seems to be simple, it underlies a complex circuit of interrelated systems. Hence, numerous physiologic systems that have pleiotropic effects and interact in complex fashion have been found to modulate blood pressure. Because of their number and complexity it is beyond the scope of the current account to cover all mechanisms and feedback circuits involved in blood pressure control. Rather, an overview of the clinically most relevant ones is presented. These systems include the heart, the blood vessels, the extracellular volume, the kidneys, the nervous system, a variety of humoral factors, and molecular events at the cellular level. They are intertwined to maintain adequate tissue perfusion and nutrition. Normal blood pressure control can be related to cardiac output and the total peripheral resistance. The stroke volume and the heart rate determine cardiac output. Each cycle of cardiac contraction propels a bolus of about 70 ml blood into the systemic arterial system. As one example of the interaction of these multiple systems, the stroke volume is dependent in part on intravascular volume regulated by the kidneys as well as on myocardial contractility. The latter is, in turn, a complex function involving sympathetic and parasympathetic control of heart rate intrinsic activity of the cardiac conduction system complex membrane transport and cellular events requiring influx of calcium, which lead to myocardial fibre shortening and relaxation and affects the humoral substances (e.g., catecholamines) in stimulation heart rate and myocardial fibre tension. 

The regulation of the total peripheral resistance also involves the complex interactions of several mechanisms. These include baroreflexes and sympathetic nervous system activity response to neurohumoral substances and endothelial factors myogenic adjustments at the cellular level, some mediated by ion channels and events at the cellular membrane and intercellular events mediated by receptors and mechanisms for signal transduction. As examples of some of these mechanisms, there are two major neural reflex arcs (Fig. 1). Baroreflexes are derived from high-pressure barorecep-tors in the aortic arch and carotid sinus and low-pressure cardiopulmonary baroreceptors in ventricles and atria. These receptors respond to stretch (high pressure) or... 

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