Tolerance explanations

Types of Tolerance Explanations of Tolerance Behavioral Pharmacology Reinforcement and Punishment Operant Principles and Drug Dependence Drug Discrimination Conflict Paradigm... 

The most essential question is why the CO-free sites are secured for H2 adsorption and oxidation. Watanabe and Motoo proposed a so-called bifunctional mechanism originally found at Pt electrodes with various oxygen-adsorbing adatoms (e.g., Ru, Sn, and As), which facilitate the oxidation of adsorbed COad at Pt sites [Watanabe and Motoo, 1975a Watanabe et al., 1985]. This mechanism has been adopted for the explanation of CO-tolerant HOR on Pt-Ru, Pt-Sn, and Pt-Mo alloys [Gasteiger et al., 1994, 1995], and recently confirmed by in sim FTIR spectroscopy [Yajima et al., 2004]. To investigate the role of such surface sites, we examined the details of the alloy surface states by various methods. 

Given the low incidence of severe withdrawal symptoms and the modest effects on the mesolimbic dopamine (reward) system, most investigators have found that cannabis has a low abuse or addiction potential. However, it has been argued that if cannabis is a non-addictive substance, why is its use so widespread and why are there so many longterm and heavy users Finally, contrary to the evidence that cannabis can produce chronic tolerance, some regular users report that they require less drug to achieve the same high, or sensitisation (Chapter 3). Three possible explanations may account for this. First, chronic users may focus on the effects that they wish to achieve. Second, the... 

The other factor affecting the use of organic nitrates is nitrate tolerance, the mechanism of which is unclear. An early explanation of tolerance was thiol depletion [68] but that now seems unlikely as their is an abundance of thiol in most tissue [69]. A more likely explanation is down regulation of the enzymes involved in the biotransformation but few details are available. An interesting suggestion is that GTN induces increased production of superoxide from the vascular wall and tolerance is caused by reaction of NO, produced enzymatically from GTN, with superoxide to give peroxynitrite and then nitrate [70] (Eq. (16)). 

As soon as fraud is suspected, a series of steps needs to be followed which have been thought out and written down as an SOP before any clinical research commenced. Where possible, additional evidence should be obtained, usually by the use of a competent QA auditor. In the meantime, only the minimum key individuals should be made aware of the problem until sufficient evidence has been obtained to establish the truth. The appropriate authorities such as the national drug industry organisation and the regulatory authorities should be informed if fraud has taken place. Sometimes, other sponsors will have reported additional evidence that fraud is taking place at a particular site. The site will need to be closed if study subjects are still being recruited and a full explanation provided to the authorities. Any clinical data collected will need to be reviewed and a decision made as to whether any of the data can be included in an analysis. To a pharmaceutical physician, fraud is never an easy situation. It usually involves a professional colleague and there is always the worry that the established facts have been misinterpreted. However, a fraudulent individual cannot be tolerated in modern clinical research. 

The results reported here indicate the potential for Bronopol (Myacide AS) as a preservative in mineral slurry systems. In particular, its ability to control organisms that are tolerant or resistant to other biocide chemistries is a valuable feature. Sondossi et alf" have reported on the activity of Bronopol against organisms that are resistant to formaldehyde. The results presented here indicate that this ability also covers BIT resistant organisms. The explanation for this may be related to some unique facet of Bronopol s mode of action and this fact is supported by published work. Overall, it suggests that Bronopol could be used in clean-up regimes to recover contaminated product. 

All compounds used had equivalent purity (see Table 11). The test design was focused on the evaluation of histological differences after a tamponade time of 6 weeks. The density of the PFCLs used was 1.32 g/ml (perfluorobutylbutane), 1.62 g/ml (perfluorohexyl-ethane) and 1.78 g/ml (PFO). There was no dose-response relationship that means there is no evidence that a higher density creates more severe histological damage. Therefore, the simple explanation of the insufficient long-term tolerance for PFCLs could not be verified. 

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