Hysteresis counterclockwise

Fig. 8 Representative compression and expansion 11/ 4 isotherms showing clockwise and counterclockwise hysteresis.

Fig. 6. Counterclockwise hysteresis appearing between hearing threshold shift and quinine plasma concentration in a subject who received two identical oral doses (dotted and solid lines) and an infusion (dashed line) of quinine. (From Paintaud G, Alvan G, Beminger E et al. The concentration-effect relationship of quinine-induced hearing impairment. Clin Pharmacol Ther 1994 55 317-23, with permission from MOSBY Inc.)...

When creating a graph of the relationship between the time course of the plasma concentrations of a drug in the body (plotted on the x-axis) and the time course of the observed drug effect (plotted on the y-axis), a loop with a counterclockwise direction may be obtained. This means that there are more than two values of effect that correspond to a single plasma concentration (Fig. 6). The phenomenon is called counterclockwise hysteresis or just hysteresis, provided that the model describes a stimulatory (positive) response. If the drug effect would be inhibitory (negative), the direction of the hysteresis would be clockwise. 

But this mechanism is also valid for VF(C0a) characterized by counterclockwise hysteresis. Under normal pressures no such dependence has been found. There are only a few literature results evidencing the high parametric sensitivity of W-C0,2[53], But these data have been obtained in the high vacuum region. 

A) Sigmoid Emax, (B) log-linear, (C) counterclockwise hysteresis loop. 

We show in Figure 13.8 that in the case of a well-behaved piezoelectric relaxation (counterclockwise hysteresis) presented in Figure 13.7, the Kramers-Kronig relations are indeed fulfilled. Closer inspection of the data show that the relaxation curves can be best described by a distribution of relaxation times and empirical Havriliak-Negami equations [19]. It is worth mentioning that over a wide range of driving field amplitudes the piezoelectric properties of modified lead titanate are linear. Details of this study will be presented elsewhere. 

Under the assumptions of the direct-link model, neither a counterclockwise (Figure 10.2) nor a clockwise hysteresis loop (Figure 10.4) will be recorded in an effect vs. concentration plot. In principle, the shape of the effect vs. concentration plot for an ideal direct-link model will be a curve identical to the specific pharmacodynamic model, relating effect with concentration, e.g., linear for a linear pharmacodynamic model, sigmoid for the sigmoid Emax model (cf. Table 10.1 and following paragraphs and sections), etc. 

The basic feature of the indirect-link model is the counterclockwise hysteresis loop that is obtained from plotting the observed values of the effect vs. the observed plasma drug concentration values, Figure 10.2. In other words, the effect is delayed compared to the plasma drug concentration and this is reflected in the effect-concentration state space. 

Figure 10.2 Normalized effect-plasma drug concentration state space for the indirect link model. As time flows (indicated by arrows) a counterclockwise hysteresis loop is formed. The rate constant for drug removal from the effect compartment ky characterizes the temporal delay, that is, the degree of hysteresis.

It is rather obvious that an indirect response mechanism, whatever the detailed processes involved, results in a counterclockwise hysteresis loop for the effect-concentration relationship, Figure 10.2. Here, however, the elaboration of the observed response is usually secondary to a previous time-consuming synthesis or degradation of an endogenous substance(s) or mediator(s). Since both the indirect-link and indirect response models have counterclockwise hysteresis effect-concentration plots, an approach based on the time of the maximum effect has been applied to furosemide data [440] for indirect (link or response) model selection. 

Fig. 6 Schematic presentation of delay between plasma concentration and effect resulting in counterclockwise hysteresis.

FIGURE 5-17. Hysteresis occurs when effect measurements are different at the same concentration.This is commonly seen aftershort-term intravenous infusions or extravascular doses where concentrations i ncrease and subsequently decrease. Counterclockwise hysteresis loops are found when concentration-effect points are joined as time increases shown by arrows) and effect is larger at the same concentration but at a later time. Clockwise hysteresis loops are similar, but the concentration-effect points are joined in clockwise order and the effect is smaller at a later time. 

Counterclockwise hysteresis loops can be caused by the accumulation of an active metabolite, sensitization to the drug, or delay in time in equilibration between serum concentration and concentration of drug at the site of action. Combined pharmacokinetic-pharmacodynamic models have been devised that allow equilibration lag times to be taken into account. 

Sensitization is defined as the opposite effect of tolerance, an increase in drug effect over time despite constant drug concentrations at the effect site, which is manifested by a counterclockwise hysteresis loop in a plot of effect vs. concentration. 

Typically, multiplicity of steady states is accompanied by hysteresis, a term derived from the Greek word meaning lagging behind. A characteristic mark of hysteresis is that the output— here the reaction rate—forms a loop, which can be oriented clockwise or counterclockwise. Hysteresis causes the reaction rate to jump up or fall down, signifying, respectively, ignition and extinction of the reaction. Fig. 7.5 shows some examples of kinetic dependences involving hysteresis. 

Figure 10.8 Comparison of CO2 produced during TAP vacuum pump-probe experiments and atmospheric flow experiments for CO oxidation over single Pt particle with the same composition of reactants, (a) A typical set of pump-probe CO2 responses (m/e = 44) for reaction at 140, 170, and 350 C. There is a shift in the amount of CO2 produced during both CO and oxygen pulses as temperature increases, (b) CO2 production observed from atmospheric flow experiment. The CO2 produced while increasing reactor temperature is less than the CO2 produced during reactor temperature decrease as shown by the counterclockwise hysteresis loop, (c) CO2 production observed from vacuum pump-probe experiment The black line represents the total CO2 yield. The circle and diamond points represent the CO2 yield on the oxygen pulse and CO pulse, respectively.

C-V Characteristics of a Ferroelectric Thin Film Sample. In the semiconductor industry, C-V curves are frequently utilized for studying the characteristics of devices. In general, a C- V curve can show ferroelectric memory effect of a ferroelectric thin film sample. A voltage applied on the sample is swept from 0 to a positive value (for example, -1-5 V), then from -h5 to -5 V and returned from to -i-5 V. It is demonstrated that the C-V curve has a counterclockwise hysteresis loop, probably due to the ferroeletric nature of the sample. This C- V hysteresis loop can indirectly reflect that a sample may have ferroelectric characteristics (Tokumitsu, 2002). However, the hysteresis characteristics of a C-V curve is not only caused by spontaneous polarization, but also included other effects, like space charge and interface charge. 

APC) (a) and (Mg2(p-C1)3-6THF) (HMDSAICI3) (GENl) (b) on a stainless steel working electrode with an area of 0.02 cm at a temperature of 21 °C. Counterclockwise arrows designate hysteresis. Scan rate is 25 mV/s and the counter and reference electrode are both magnesium... 

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