Rodent studies analysis

In the case of atrazine, the most widely used triazine, refinement of the conservative Tier I estimate for all populations results in at least a 200-fold reduction in exposure and risk. In addition, the total exposure and risk for atrazine using a Tier III approach is approximately 138000-fold to 450000-fold less than the chronic NOAEL obtained from a rodent study. A 600-fold to 1600-fold difference exists between the NOAEL and maximum theoretical exposure and risk when tolerance values are utilized. Further refinement of the estimate using Tier IV methodology would result in even lower exposure and risk, since this Tier III analysis used data generated from structured field trials (maximum label rate and minimum preharvest interval). 

In rodent stroke models, statin pretreatment has been shown to reduce infarct volumes and improve outcomes. Similarly, several clinical studies have shown that prior statin use reduced the severity of acute ischemic stroke and myocardial infarction. Recent studies indicate that beneftt can be achieved even when treatment is initiated after the onset of symptoms. In rodents, atorvastatin and simvastatin have been shown to reduce the growth of ischemic lesions, enhance functional outcome, and induce brain plasticity when administered after stroke onset. A retrospective analysis of the population-based Northern Manhattan Stroke Study (NOMASS) showed that patients using lipid-lowering agents at the time of ischemic stroke have a lower incidence of in-hospital stroke progression and reduced 90-day mortality rates. Retrospective analysis of data of the phase III citicoline trial showed... 

In addition to bcl-2, another hitherto completely unexpected target for the actions of chronic lithium and VPA has been identified from the mRNA RT-PCR DD study described above. Another clone, also derived from a transcript whose levels were increased by both lithium and VPA, shows very strong homology to a human mRNA-binding protein, the AUH protein ([54, 55] Genbank accession number X79888). BESTFIT analysis revealed 83.2% sequence homology between this rodent clone and the human AUH protein [54—56]. 

Food and Drug Administration (FDA) (2001). Guidance for Industry Statistical Aspects of the Design, Analysis and Interpretation of Chronic Rodent Carcinogenicity Studies of Pharmaceuticals. USDHEW, Washington, D.C. 

The limited availability of suitable human tissue for experimental studies and the rather low CYP expression level in the human lung, compared to that found in rodents [111], have notably limited identification of the lung CYP isoforms. By means of RT-PCR, it has been possible to qualitatively demonstrate the presence of several CYP mRNAs in the human bronchial mucosa, namely CYP1A1, 2A6, 2B6, 2C, 2E1 and 3A5, whereas the expression of CYP1A2, 2D6, 3A4 and 3A7 could be detected only in some samples (Table 10.1) [109, 111, 112], Immunohistochemical analysis has shown the significant expression of CYP enzymes in different pulmonary cells including... 

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