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Diltiazem

By P. Phil. Brooklyn Law School.

Despite its microscopic dimensions (often less than 1 micron in thickness) order 60mg diltiazem with mastercard, this living membrane is a multifunctional organ whose health is essential to normal vascular physiology and whose dysfunction can be a critical factor in the pathogenesis of vascular disease buy diltiazem 60mg lowest price. Anatomically, the endothelium forms the physical boundary separating the intravascular compartment from all of the tissues and organs of the body. As long as this cellular membrane remains intact and is functioning normally, a non-thrombogenic surface is presented to the circulating blood, thus allowing it to remain fluid and perform its nutritive functions unimpeded by intravascular clotting. Physical disruption of the endothelial lining, even on a microscopic scale, elicits an immediate hemostatic response, involving localized activation of the coagulation cascade and the adherence and aggregation of platelets, an adaptive reaction that serves to limit blood loss at sites of injury. Conversely, acute or chronic impairment of the non-thrombogenic properties of the intact endothelial lining (a form of endothelial dysfunction, see below) can be an important predisposing factor for intravascular thrombosis. Because of its unique anatomical location the endothelium also functions as a selectively permeable barrier. Macromolecules encountering various regional specializations of the endothelium, including cell surface glycocalyx, cell-cell junctional complexes, microvesicles, transcellular channels and subendothelial extracellular matrix, are enhanced or retarded in their movement from (or into) the intravascular space. Selectivity of this barrier function typically reflects the size and/or charge of the permeant molecule, but may also involve active metabolic processing on the part of the endothelial cell. Enhanced permeability to plasma macromolecules, such as albumin, is a hallmark of acute inflammation, and, in the case of lipoproteins, is an important part of atherosclerotic lesion development. Pathophysiologic stimuli, as well as therapeutic drugs, that can modulate this endothelial function thus have potential clinical relevance. Another functionally important consequence of the location of the endothelium is its ability to monitor, integrate and transduce blood- borne signals. At every site in the circulatory system they are sensing and responding to the local pathophysiological milieu, and can help propagate these responses transmurally, from the intimal lining into the walls of larger vessels (e. As will be considered in more detail below, this sensing and transducing function extends beyond classical humoral stimuli to the biotransduction of distinct types of mechanical forces generated by pulsatile blood flow (e. Endothelium is capable of generating a diverse array of biologically active substances, including lipid mediators, cytokines, growth factors and other hormone-like substances, many of which serve as important biological effector molecules, influencing the behavior of multiple cells and tissues. Some act directly within their cell of origin in a so-called autocrine mode, whereas others act on adjacent cells (within the vessel wall or in the blood) in a paracrine mode. In addition to being the source of cytokines, growth factors and hormones, the endothelium also is an important target of their actions. Indeed, the capacity for the endothelium to undergo, local or systemic, “activation” in response to such stimuli, with resultant dramatic changes in functional status, is an important aspect of its biology and pathobiology. It provides a conceptual model that encompasses both physiological adaptation and pathophysiological dysregulation. Given its interface location, integrating and transducing capability, and the vast repertoire of its biologically active products, the endothelium plays a pivotal role in a series of “pathophysiologic balances. In each, endothelial-derived agonists and antagonists dynamically interact in the regulation of important processes that can have both local and systemic ramifications, such as hemostasis and thrombosis, vascular tone, vascular growth and remodeling, and inflammatory and immune reactions. At any given time, factors influencing the activation state or functional integrity of the endothelium determine the relative set-points of each of these balances. The controlled expression of certain of these pro- thrombotic factors in response to local vascular trauma (e. Similarly, imbalances in endothelial-derived smooth muscle relaxants versus endothelial-derived vasoconstrictors can influence local circulatory dynamics, as well as systemic blood pressure.

This is especially observed in hysterical conditions buy diltiazem 180mg on line, in hystero-epilepsy and in hypochondriasis order diltiazem 60mg with visa. It arrests hysterical paroxysms and produces quiet and rest with a pleasant sense of exhilaration. In nervousness, especially that of weakened and exhausted conditions, and of children, it is soothing, and often wards off spasms. In spasmodic conditions of the stomach and bowels with tympanites, in the absence of active inflammation it is a remedy long used. In accumulations of gas in the stomach or bowels it has been used to, the best advantage. In spasmodic bronchial affections, in whooping cough, and in asthma it was a favorite with the older doctors. In the bronchial catarrhs of the aged and infants it has been given with advantage, especially if nervous depression was present. A three-grain pill was the celebrated “Keeley cure” for la grippe, and those who have used the remedy in epidemic influenza are usually enthusiastic in its praise. It has been recommended during the progress of low fevers, where the nervous system is greatly debilitated, as in typhus, typhoid and typho- pneumonia. Wherever the nervous system has received the effect of a protracted prostrating disease, it can be given with advantage. Murawieff Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 217 advised it in both acute and chronic pulmonary disease, through its influence upon the nervous system. Probably it influences the circulatory and respiratory functions, supporting them under the strain of protracted inflammation. The remedy has been used in stomach disease, diarrhea, in dysentery, and in cholera. When the nervous system is enfeebled in hysteria, and in delirium tremens, it is a good remedy. In chlorosis, anemia with nervous phenomena, in leucorrhea and gleet, it is to be advised. In one case, there was contraction of muscles of the shoulders with inability to raise the arms, with severe neuralgic pain, weakness of the nervous system, and violent attacks of the heart. There were rheumatic pains in the feet and lower part of the legs which prevented the patient from walking except with the aid of a crutch. There was gradual improvement, and the patient ultimately made a satisfactory recovery. Cowen gives manaca in fifteen-drop doses, with salicylate of sodium in acute rheumatism. Hopkins gives manaca in muscular rheumatism in four-drop doses every two or three hours. Therapy—This agent operates upon the stomach and digestive apparatus directly, influencing the tone of the glandular organs of the entire digestive tract. It is a stomachic tonic of considerable power, exercising its best influence when the apparatus is impaired by protracted disease. Under these circumstances it is also a stimulant and astringent to the secreting surfaces, correcting excessive night sweats common to such a condition, controlling the diarrhea and dysentery where there are relaxed and atonic mucous membranes.

If the body falls from a sufficiently great height buy diltiazem 60mg, the velocity reaches a magnitude such that the force due to air resistance is equal to the weight generic diltiazem 180 mg amex. Past this point, the body is no longer accelerated and continues to fall at a constant velocity, called the terminal velocity vt. At the terminal velocity, the downward force of gravity is canceled by the upward force of air resistance, and the net acceleration of the body is zero. The weight of an object is proportional to the volume, which is in turn proportional to the cube of the linear dimension L of the object, 3 W ∝ L The area is proportional to L2. With proper training, a person can jump from a height of about 10 m 42 Chapter 3 Translational Motion without sustaining serious injury. From this height, a person hits the ground at a speed of v 2gs 14 m/sec (46 ft/sec) Let us assume that this is the speed with which any animal can hit the ground without injury. At this speed, the force of air resistance on an animal the size of man is negligible compared to the weight. A simple calculation shows that a mouse can fall down a 100-m mine shaft without severe injury. Air friction has an important effect on the speed of falling raindrops and hailstones. Without air friction, a 1-cm diameter hailstone, for example, falling from a height of 1000 m would hit the Earth at a speed of about 140 m/sec. As it is, air friction slows the hailstone to a safe terminal velocity of about 8. The energy required to perform the work is obtained from the chemical energy in the food eaten by the animal. In general, only a small fraction of the energy consumed by the muscles is converted to work. For example, in bicycling at a rate of one leg extension per second, the efficiency of the muscles is 20%. In other words only one fifth of the chemical energy consumed by the muscle is converted to work. The energy consumed per unit time during a given activity is called the metabolic rate. In most cases, the efficiency of the muscles in converting caloric food energy to work is less than 20%. We will calculate the amount of energy consumed by a 70-kg person jump- ing up 60 cm for 10 minutes at a rate of one jump per second. The external mechanical work performed by the leg muscles in each jump is Weight × Height of jump 70 kg × 9. In the calculation, it is assumed that most of the work done in running is due to the leg muscles accelerating each leg to the running speed v, and then decelerating it to 0 velocity as one leg is brought to rest and the 1 2 other leg is accelerated. As is shown in Exercise 3-9, typically, a 70-kg person (leg mass 10 kg) running at 3 m/sec (9-min. Theenergyrequiredtoovercome air resistance in running is calculated in Exercise 3-10. In connection with the energy consumption during physical activity, we should note the difference between work and muscular effort. Work is defined as the product of force and the distance over which the force acts (see Appendix A). When a person pushes against a fixed wall his/her muscles are not performing any external work because the wall does not move.

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