Linear dose dependence

Cl-988 has been found to reduce the behavioral stress in marmosets exposed to a human threat [Hughes et al. 1990]. L-365,260 can antagonize the behavioral effects of exposition to the odor of a cat in rats and suppress the behavioral reaction of mice to the calls of an owl, an effect also found with LY 288513 (Hendrie and Dourish 1994]. Thus, evidence suggests an anxiolytic activity of CCK-B antagonists. The activity seems more evident in etho-logically based models of anxiety than in conflict-based tests and does not follow a linear dose-dependent relationship but rather a bell-curve one. Also, most studies point to a selectivity of CCK-B antagonists, but not CCK-A antagonists, for anxiolytic effects. 

The H2 antagonists exhibit competitive inhibition at the parietal cell H2 receptor and suppress basal and meal-stimulated acid secretion (Figure 62-2) in a linear, dose-dependent manner. They are highly selective and do not affect H j or H3 receptors (see Chapter 16). The volume of gastric secretion and the concentration of pepsin are also reduced. 

Watanabe, P. J., Young, J. D. and Gehring, P. J. "The Importance of Non-Linear (Dose-Dependent) Pharmacokinetics in Hazard Assessment" J. Environ. Path. Toxicol. (1977),... 

The TL peaks at about 415 K in (a), (b) and (c) may be of some interest in dosimetry. These peaks become dominant at higher doses. In the case of CsCkEu the authors show its linear dose response and conclude that it may suit for radiation dosimetry. In (b) and (c) the dose response is sublinear. This conclusion seems however to have resulted from overlap with other peaks. Proper resolution of the peaks by prewarming to a temperature close to 400 K or by total-glow-curve computer fitting may show linear dose dependence also for the Sm- and Tb-doped phosphors. 

Heavy drinking over an extended period of time can damage almost every organ system in the body. Chronic illness is almost inevitable following prolonged alcohol abuse and the risk of cancer is increased, often in a linear, dose-dependent manner. Unfortunately, women are more prone to alcohol-related liver, heart and brain damage than men, as well as certain types of cancer. 

The toxic effects model uses concentration-time profiles from the respiratory and skin protection models as input to estimate casualty probabilities. Two approaches are available a simple linear dose-effect model as incorporated in RAP and a more elaborate non-linear response model, based on the Toxic Load approach. The latter provides a better description of toxic effects for agents that show significant deviations of simple Haber s law behaviour (i.e. toxic responses only depend on the concentration-time product and not on each quantity separately). 

A less invasive procedure that could provide a indication of DNA adduct formation is measurement in the urine of the mercaptic acid S-[2-N -guanl)ethyl]-N-acetylcysteine. Excretion of this metabolite into the urine of rats occurs in a dose-dependent, linear manner after intraperitoneal administration of 1,2-dibromoethane (Kim and Guengerich 1989). This biomarker has not been looked for to date in humans suspected to have exposure to 1,2-dibromoethane. 

The time course of the effect and of the concentration in plasma are not identical, because the concentration-effect relationships obeys a hyperbolic function (B cf. also p. 54). This means that the time course of the effect exhibits dose dependence also in the presence of dose-linear kinetics (C). 

An important consequence of this interpretation is the fact that the magnitude of the quadratic term (but not the linear one) depends on dose rate. Indeed, in most cases, sublesions undergo repair and thus the lower the dose rate [i.e., the larger the (average) time interval that separates the formation of the two sublesions, the lower the yield of intertrack lesions]. With this, the linear-quadratic equation becomes ... 

The effectiveness of CCK-4 in provoking panic responses also appears to be dose dependent. In a double-blind dose-response study [Bradwejn et al. 1992b] of CCK-4 [0, 10, 15, 20, and 25 0g] in patients with panic disorder, a significant linear relationship was found for the number and sum intensity of symptoms evoked with CCK-4. None of the patients panicked with placebo. The difference between treatments in panic fre-... 

Neural membranes isolated from primary astrocyte cultures established from newborn Sprague-Dawley rat cerebella were exposed to 3, 6 or 9 mmol/L ethylbenzene for 1 h. ATPase activity decreased linearly with log concentration of ethylbenzene (Naskali et al., 1994). In the same astrocyte cultures, ethylbenzene (3, 6 or 9 mmol/L 1-h exposure) decreased in a dose-dependent manner the activity of important membrane integral proteins such as NaVK+-ATPase and Mg -ATPase (Vaalavirta Tahti, 1995). 

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