Physiological effect

An understanding of how these effects may be related to the expression of individual isoforms is now beginning to emerge. It is known that in immature rats of either gender, P450s 2A1, 2D6, and 3A2 predominate, whereas in mature rats, the males show a predominance of P450s 201, 2C6, and 3A2 and the females P450s 2A1, 2C6, and 202. 

The effect of senescence on the metabolism of xenobiotics has yielded variable results. In rats monooxygenase activity, which reaches a maximum at about 30 days 

Aspirin (acetylsalicylic acid) and other salicylates are still a common cause of human poisoning, both therapeutic and suicidal, and account for a significant number of deaths each year. Although the toxic effects have a biochemical basis, some of the effects caused are clearly physiological, and consequently, it has been used as an example in this category. 

The therapeutic blood level is greater than 150 mg L-1 but symptoms of toxicity occur at blood levels of around 300 mg L-1. Therefore, knowledge of the blood level is important, particularly when aspirin is given in repeated doses. In children, therapeutic overdosage is responsible for the majority of fatalities from aspirin. When an overdose is suspected, measurement of the plasma level on two or more occasions will allow an estimate to be made of the severity of the overdose and whether the plasma level has reached its maximum. For interpretation of the blood level, the Done nomogram can be used. An overdose of 50 to 300 mg tablets in adults will give rise to moderate to severe toxicity and a blood level of 500 to 750 mg L-1 at 12 hours. The blood level must be interpreted with caution, however, because 

the presence of metabolic acidosis will complicate the interpretation, because this will alter the distribution of salicylic acid (see below), and 

with therapeutic overdose after repeated dosing, tissue levels may be higher than expected from the blood level. 

Salicylic acid is mainly responsible for the toxic effects of aspirin, and it has a number of metabolic and physiological effects some of which are interrelated (Fig. 7.58)  

Rhythmic changes in biochemical constituents have been known for many years, and the terms daily, diurnal, 24-hour, diel, and mycthemeral have been used to describe them (B26). With the realization that these cycles were not always of 24-hour duration and varied from 18 to 33 hours, the term circadian was used (H3), but most recently, episodic secretion has been introduced to emphasize the fact that secretory glands experience periods of quiescence and then spurts of activity (H7). 

Rhythmic variation can be important in the interpretation of laboratory data. Although ideally it would be appropriate to obtain specimens from all patients at the same time of the day, this is not practical and there are a number of constituents whose values must be reviewed with the realization that the concentration can vary by 100% or more during a 24-hour period. 

A rhythmic variation has been observed in levels of plasma hydroxy-corticosteroids (A9, B13, D9) and in the excretion of 17-ketosteroids (P7). As shown in Table 5, urinary excretions of potassium, sodium, chloride, 17-hydroxycorticosteroids and water have been reported to be greatest between 10 am to noon and lowest between 4 am and 6 am (S21). In this study it was shown that within 5 weeks subjects could acclimate to similar patterns for a 21-hour, rather than a 24-hour, day. Heilman and his associates reported that about half of the day s cortisol production is achieved in the early morning hours during sleep and that production is minimal between noon and 10 pm (H7). In one study the plasma cortisol in normal men was 24.6 5.5 /xg/100 ml at 7 am 13.1 3.4 fig/100 ml at 9 am 11.8 fig/100 ml at noon 9.1 2.3 jag/100 ml at 7 PM and 6.3 /ig/100 ml at 10 pm (A9). 

Although many workers believe that light is the major controller of these rhythms, it has been shown that social cue, rather than the absence of light, is the inducing factor. Subjects maintained in the dark demon- 

Excretory Rhythms Determined in Adults during a Normal Daily Routine  

Thyroid hormone enhances cardiac contractility and exerts a positive chronotropic effect on the heart, increasing heart rate by a mechanism that may involve more than a potentiation of the )S-adrenergic effect. In the 

Metabolism of T3 andT4. To, Thyronine 3,3 -T2, 3,3 -diiodothyronine 3 -T, 3 -iodothyronine TETRAC, 3,3, 5,5 -tetraiodothyroacetic acid TRIAC, 3,3, 5-triiodothyroacetic acid. 

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Rec tor. Receptors are membrane-bound or soluble proteins or protein complexes exerting a physiological effect after binding of an agonist. 

Epinephrine is also known as adrenaline and is a hormone with profound physiological effects designed to prepare the body for fight or flight... 

Corticosteroids exhibit a wide range of physiological effects One important func tion IS to assist m maintaining the proper electrolyte balance m body fluids They also play a vital regulatory role m the metabolism of carbohydrates and m mediating the alter gic response... 

Both RDX and HMX are stable, crystalline soHds, somewhat less sensitive to impact than PETN. Both may be handled with no physiological effect if appropriate precautions are taken to assure cleanliness of operations. Both RDX and HMX detonate to form mostiy gaseous, low molecular weight products and some intermediate formation of soHd carbons. The calculated molar detonation products of RDX are 3.00 H2O, 3.00 N2, 1.49 CO2, and 0.02 CO. RDX has been stored for as long as 10 months at 85°C without perceptible deterioration. 

Health Safety. PET fibers pose no health risk to humans or animals. Eibers have been used extensively iu textiles with no adverse physiological effects from prolonged skin contact. PET has been approved by the U.S. Eood and Dmg Administration for food packagiug and botties. PET is considered biologically iuert and has been widely used iu medical iaserts such as vascular implants and artificial blood vessels, artificial bone, and eye sutures (19). Other polyester homopolymers including polylactide and polyglycoHde are used iu resorbable sutures (19,47). 

Table 3 shows the toxicological properties of selected ketones. A detailed review of the physiological effects of exposure to methyl ethyl ketone and methyl isobutyl ketone has been documented (6). 

Methanol is not classified as carcinogenic, but can be acutely toxic if ingested 100—250 mL may be fatal or result in blindness. The principal physiological effect is acidosis resulting from oxidation of methanol to formic acid. Methanol is a general irritant to the skin and mucous membranes. Prolonged skin contact with methanol vapor or Hquid can cause dermatitis. Methanol vapor can cause eye and respiratory tract irritation, nausea, headaches, and dizziness. 

Catecholamines. The catecholamines, epinephrine (EPl adrenaline) (85), norepinephrine (NE noradrenaline) (86) (see Epinephrine and norepinephrine), and dopamine (DA) (2), are produced from tyrosine by the sequential formation of L-dopa, DA, NE, and finally EPl. EPl and NE produce their physiological effects via CC- and -adrenoceptors, a-Adrenoceptors can be further divided into CC - and a2-subtypes which in turn are divided... 

Ammonia is a strong local irritant which also has a corrosive effect on the eyes and the membranes of the pulmonary system. Vapor concentrations of 10,000 ppm are mildly irritating to the skin, whereas 30,000 ppm may cause bums. The physiological effects from inhalation are described in Table 16. Prolonged, intentional exposure to high levels of ammonia is unlikely because its characteristic odor can be detected at levels as low as 1 —5 ppm (94). The real danger occurs when escape is impossible, or the exposure victim has lost consciousness. 

In other applications of CT, orally administered barium sulfate or a water-soluble iodinated CM is used to opacify the GI tract. Xenon, atomic number 54, exhibits similar x-ray absorption properties to those of iodine. It rapidly diffuses across the blood brain barrier after inhalation to saturate different tissues of brain as a function of its lipid solubility. In preliminary investigations (99), xenon gas inhalation prior to brain CT has provided useful information for evaluations of local cerebral blood flow and cerebral tissue abnormalities. Xenon exhibits an anesthetic effect at high concentrations but otherwise is free of physiological effects because of its nonreactive nature. 

Phosphorothioates generally protect normal tissues more than tumors. Tumor protection reported in some animal studies can pardy be explained by physiological effects of the particular dmgs, which are specific to rodents (4). WR-2721 does not appear to protect human and most animal tumors, apparentiy because of the low availabiUty of the dmg to tumor cells (4). Many tumors appear to have a reduced capillary density (44), which may mean that these tumors have altered levels of alkaline phosphatase, the enzyme that converts WR-2721 to WR-1065. A reduced abiUty of thiols to protect the hypoxic cells characteristic of many tumors may also contribute to their selectivity for normal tissues. The observation that WR-1065 protects cultured normal human fibroblasts, but not fibrosarcoma tumor cells, suggests that additional factors may contribute to the selectivity of radioprotection by WR-2721 m vivo (18). 

Toxicity data for the acid are as follows oral LD q (i ts), 1600 mg/kg and oral LD q (mice), 3100 mg/kg (49). The physiological effects of sulfamic acid and ammonium sulfamate are described in Reference 50. 

The uses of corticosteroid antiinflammatory dmgs in veterinary medicine are many and varied. In the intact animal, the glucocorticoids and mineralcorticoids are produced in the adrenal glands. Exogenous compounds are, therefore, used for their glucogenic physiologic effect in cases where the... 

Physiological Effects. The sulfur and nitrogen mustards act first as cell irritants and finally as a cell poison on all tissue surfaces contacted. The first symptoms usually appear in 4—6 h (4). The higher the concentration, the shorter the interval of time between the exposure to the agent and the first symptoms. Local action of the mustards results in conjunctivitis (inflammation of the eyes) erythema (redness of the skin), which may be followed by blistering or ulceration and an inflammatory reaction of the nose, throat, trachea, bronchi, and lung tissue. Injuries produced by mustard heal much more slowly and are much more Fable to infection than bums of similar intensity produced by physical means or by other chemicals. 

Trichloroethylene is acutely toxic, primarily because of its anesthetic effect on the central nervous system. Exposure to high vapor concentrations is likely to cause headache, vertigo, tremors, nausea and vomiting, fatigue, intoxication, unconsciousness, and even death. Because it is widely used, its physiological effects have been extensively studied. 

The physiological effect of a particular lens can be determined by measuring the increased thickness of the cornea after lens wear studies have shown the relationship between the DkjD of a lens and the subsequent swelling of the underlying cornea (20,21). 

Dietary fiber is a mixture of simple and complex polysaccharides and lignin. In intact plant tissue these components are organized into a complex matrix, which is not completely understood. The physical and chemical interactions that sustain this matrix affect its physicochemical properties and probably its physiological effects. Several of the polysaccharides classified as soluble fiber are soluble only after they have been extracted under fairly rigorous conditions. 

S. M. Pilch, Physiological Effects and Health Consequences of Dietay Fiber, Life Sciences Research Office, Federation of American Societies for Experimental Biology, Bethesda, Md., 1987. 

Zone-1 - Usually no reaction Zone-2 - Usually no dangerous physiological effect... 

In general, clinical studies provide evidence on the effects of air pollutants under reproducible laboratory conditions. The exposure level may be accurately determined. The physiological effect may be quantified, and the health status of the subject is well known. This type of study can determine the presence or absence of various endpoints for a given sample group exposed to short-term, low-level concentrations of various air pollutants. 

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