Toxicant detection, improvements

RISK FOR INEFFECTIVE TISSUE PERFUSION RENAL When the patient is taking a drag tiiat is potentially toxic to die kidneys, die nurse must carefully monitor fluid intake and output. In some instances, die nurse may need to perform hourly measurements of die urinary output. Periodic laboratory tests are usually ordered to monitor the patient s response to therapy and to detect toxic drag reactions. Seram creatinine levels and BUN levels are checked frequentiy during the course of therapy to monitor kidney function. If the BUN exceeds 40 mg dL or if the serum creatinine level exceeds 3 mg cIL, the primary health care provider may discontinue the drug therapy or reduce the dosage until renal function improves. 

Improvements in the monitoring and operation of incinerators could minimize the accidental release of hazardons efflnents. In particular, fast-acting, continuous, on-line monitors are needed to detect excursions in operating conditions that could lead to toxic emissions. 

In a different way, metallic-core nanoparticles [346-349] (prepared cf. Section 3.10) equipped with biocompatible coats such as L-cysteine or dextrane may be exploited for highly efficient and cell-specific cancer cell targeting, i.e., for improving diagnosis and therapy of human cancer. In a recent proof-of-principle experiment an unexpectedly low toxicity of the L-cysteine-covered cobalt nanoparticles was demonstrated [433] For diagnostic purposes, it is expected to use the advantageous magnetic properties of the metallic-core nanoparticles to obtain a contrast medium for MRI with considerably increased sensitivity, capable to detect micro-metastases in the environment of healthy tissues [434 37]. 

Not only is it difficult to detect effects on male fertility because of group-size considerations, effects on male fertility mediated by decreased sperm production are also difficult to detect because of the normally huge excess of sperm included in a rat ejaculate. Sperm production can be decreased by up to 90% without effect on fertility (either pregnancy rate or litter size) in the rat. This is not the case for men, so the sperm excess in the rat represents a serious flaw in the rat model (see Working, 1988). To address this deficiency and improve the sensitivity of the model, it is advisable to determine the effects of the test agent on testes weights, testicular spermatid counts, and histopathology of the testes (preferably plastic sections) in the male fertility study and/or the 14-week toxicity study. In some cases, these parameters may be more predictive of possible effects on male fertility in humans than the fertility rate in rats. 

Accordingly, the use of flow cytometry can improve the design of toxicity bioassays, as the detection limit of this apparatus includes cellular concentrations equal to those of microalgal populations found in natural conditions. Comparison of compositions utilised in some known toxicity tests for microalgaes are shown in Table 7.1.1. 

It is common practice in pharmaceutical industry to generate salt forms of a drug substance to improve solid-state properties and solubility. CE has proven its ability to analyze reliably organic acids (direct, indirect detection) and alkaline/earth alkaline metals and basic amino acids. For basic drugs, a non-toxic organic acid or inorganic acid is chosen as counterion. Acidic drug substances will usually be deprotonated by alkaline and earth alkaline... 

The conclusion seems inescapable that random measurements of plasma phenytoin levels are useless apart from detecting suspected drug defaulters or confirmation of gross toxicity. The optimum concentration for any individual patient must be determined and regular monitoring carried out thereafter to check that this level is maintained. Thus it should be possible to improve seizure control even in severely affected patients without precipitating toxicity. 

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