Modifications side effects

Modem cancer therapy has been primarily dependent upon surgery, radiotherapy, chemotherapy, and hormonal therapy (72) (see Chemotherapeutics,anticancer Hormones Radiopharmaceuticals). Chemotherapeutic agents maybe able to retard the rate of growth, but are unable to eradicate the entire population of neoplastic cells without significant destmction of normal host tissue. This serious side effect limits general use. More recentiy, the immunotherapeutic approach to cancer has involved modification and exploitation of the cellular and molecular mechanisms in host defense, regulation of tissue proliferation, tissue differentiation, and tissue survival. The results have been more than encouraging. 

The natural prostanoids have myriad biological effects and held great promise as potential therapeutic agents in numerous diseases. The natural prostanoids, however, also have three notable drawbacks which medicinal chemists have tried to overcome by molecular modification in order to produce acceptable dmg candidates. These drawbacks are rapid metaboHsm which results in lack of activity if taken orally and a short duration of action, numerous side effects due to their multiplicity of biological activities, and poor chemical stabiUty, a characteristic especially pronounced in PGE, -D, and -I stmctures. 

Although the antibacterial spectmm is similar for many of the sulfas, chemical modifications of the parent molecule have produced compounds with a variety of absorption, metaboHsm, tissue distribution, and excretion characteristics. Administration is typically oral or by injection. When absorbed, they tend to distribute widely in the body, be metabolized by the Hver, and excreted in the urine. Toxic reactions or untoward side effects have been characterized as blood dyscrasias crystal deposition in the kidneys, especially with insufficient urinary output and allergic sensitization. Selection of organisms resistant to the sulfonamides has been observed, but has not been correlated with cross-resistance to other antibiotic families (see Antibacterial AGENTS, synthetic-sulfonamides). 

Control of Plant and Process Modifications Many accidents have occurred because plant or process modifications had unforeseen and unsafe side effects (Sanders, Management of Change in Chemical Plants Learning from Ca.se Histories, Butterworth-Heinemann, 1993). No such modifications shoiild therefore be made until they have been authorized by a professionally quahfied person who has made a systematic attempt to identify and assess the consequences of the proposal, by hazard and operability study or a similar technique. When the modification is complete, the person who authorized it... 

How can we prevent modifications from producing unforeseen and undesirable side effects References I and 2 propose a three-pronged approach ... 

Despite these intense efforts to test different chemical modifications, there is so far little success in developing potent and safe antivirals. For hepatitis C virus (HCV), McHutchison et al. reported in vivo side effects of a 20-nucleotide PS-modified ohgonucleotide (ISIS-14803) (McHutchison et al. 2006). In a test group of 28 patients, only 3 patients responded to the treatment by a reduction in the HCV viral load. The researchers concluded that further studies are needed to evaluate this novel agent and its side effects. Previously, ISIS Pharmaceuticals reported a 3.8 log reduction in plasma virus in patients with chronic HCV infection, using ISIS-14803 (www.isispharm.com). 

Every modification in design, as well as remedial actions, must be made after due consideration of building physics. Otherwise negative side effects can occur. Examples are locally high relative humidity in air, condensation of moisture and development of mold. With due consideration to the constraints laid by building physics, however, modifications to radon safe design can give positive tradeoffs as reduced possibility for moisture transport and development of mold. 

Most of the antiemetic clinical trials in the last decade have involved metoclopramide (1) either as a single agent or in combination with other drugs. Similarly, most of the chemical modification studies have been designed to optimize antiemetic and/or gastroprokinetic properties of metoclopramide and to eliminate undesirable CNS side-effects which are the consequence of its dopamine D2 receptor blockade [1-3]. 

In many applications, modification of PET fiber properties is desirable in order to enhance certain features of the product or to enhance the process of converting fibers into finished goods. In these cases, most of the basic PET fiber properties are acceptable but certain enhancements are desired, even at the expense of other properties or costs that will be affected by the modification. These side effects are always present it is the goal of fiber development personnel to engineer the best compromise. 

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