Cell and Animal Studies

Exposure of uni- or multicellular organisms (bacteria, yeasts, plants, or animals) to Cr(VI) at 295-310 K typically led to the observation of single Cr(V) signals with giso 1.98 [66,88,97,106-110], which in some cases showed partially 

We wish to acknowledge the many contributions of our coworkers and collaborators that are listed in the references. The research has been supported by the Australian Research Council (ARC) Large and Discovery grants (to P.A.L. includ- 

Levina A, Codd R, DUlan CT, Lay PA. 2003. Chromium in biology toxicology and nutritional aspects. Proginorg Chem 51 145-250. 

Intemational Agency for Research on Cancer (lARC). 2001. Overall evaluations of carcinogenicity to humans, http //www.iarc.fr. 

Steinpress MG, Ward AC. 2001. The scientific process and HoU3nvood the case of hexavalent chromium. Ground Water 39(3) 32l-322. 

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Figure 13.1 (a) Translational research strategies to predict human safety and efficacy based on in vitro studies (in animal and human cells) and animal studies. (b) Use of biomarkers and imaging techniques to increase the predictability of drug R D. 

Dietary Phytochemicals and Health Benefits Evidence from Cell and Animal Studies... 

The first reports on cell and animal studies were published in 2008. If animal studies are also discussed in the cited work, they will be discussed in the next section. Das and Tan [44] used amine-functionalised Y2O3 co-doped with, among others, Er " " and Yb and showed that the (acute) cytotoxicity to human hepatocellular carcinoma (Hep-G2) cells is very low. 

A limited study in animals also presents evidence for increased susceptibility to Streptococcus zooepidomicus (Aran d et al. 1986). Immune system effects observed in mice exposed orally to trichloroethylene included inhibition of cell-mediated immunity, delayed type hypersensitivity, and inhibition of antibody-mediated immunity (Sanders et al. 1982). Female mice appeared to be more sensitive than male mice. A study in which a susceptible strain of mice was treated with intraperitoneal injections of trichloroethylene suggests that trichloroethylene can accelerate the autoimmune response (Khan et al. 1995). The immune system may be a sensitive end point for toxic effects from low-level exposure to trichloroethylene however, no firm conclusions can be drawn from the available information. Additional human and animal studies are needed to better characterize this end point and determine the potential for immunological effects for people exposed to trichloroethylene at hazardous waste sites. 

Curcumin (diferuloyl methane) is the main pigment of turmeric. It is widely used as a colorant and preservative agent. No data regarding its daily intake in western countries are available intake may reach 80 to 200 mg in adult Indians. To date, no study has explored the effect of curcumin consumption on the incidence of diseases, but many beneficial effects on health have been reported in cell and animal models. These include anti-carcinogenic, anti-diabetic, anti-atherosclerotic, and anti-Alzheimer s disease properties. ... 

Rader, DJ., and Dugi, KA., 2000, The endothelium and hpoproteins insights from recent cell biology and animal studies, Semin. Thromb. Hemost.26 521-528. 

The effects of 1,4-dichlorobenzene ingestion on hematological parameters reported in both human and animal studies indicate that this is an area of potential concern for humans exposed to 1,4-dichlorobenzene. Possible effects in humans have been associated with red blood cells anomalies. Because of sex and species differences seen in animal studies (i.e., effects on red blood cells in rats and effects on... 

Excitement about ES-derived cells has been fueled by several reports of laboratory and animal studies. In Parkinson s disease, symptoms result from a loss of cells that produce a critical signal molecule. Cells that produce the signal were created in the lab from mouse ES cells. When injected into the brain, they reduced symptoms in mice with a form of Parkinson s disease. Strains of rats and mice have been developed or discovered that are unable to produce myelin, the fatty insulation that normally covers the nerve fibers of the brain and spinal cord. Injection of insulation-producing cells generated from mouse ES cells produced myelin on the nerve fibers of these animals. 

Preliminary in vitro and animal studies of the effects of silymarin and silybinin have been carried out with several cancer cell lines. In murine models of skin cancer, silybinin and silymarin were said to reduce tumor initiation and promotion. Induction of apoptosis has also been reported using silymarin in a variety of malignant human cell lines (eg, melanoma, prostate, leukemia cells, bladder transitional-cell papilloma cells, and hepatoma cells). Inhibition of cell growth and proliferation by inducing a Gx cell cycle arrest has also been claimed in cultured human breast and prostate cancer cell lines. The use of milk thistle in the clinical treatment of cancer has not yet been adequately studied but preliminary trials are under way. 

Oxidative stress is now recognized as an important etiological factor in the causation of several chronic diseases including cancer, cardiovascular diseases, osteoporosis, and diabetes. Antioxidants play an important role in mitigating the damaging effects of oxidative stress on cells. Lycopene, a carotenoid antioxidant, has received considerable scientific interest in recent years. Epidemiological, tissue culture, and animal studies provide... 

Owing to thalidomide s serious toxicity profile, considerable effort has been expended in the development of analogs. Immunomodulatory derivatives of thalidomide are termed IMiDs. Some IMiDs are much more potent than thalidomide in regulating cytokines and affecting T cell proliferation. CC-5013 (Revimid) is an IMiD that in in vitro and animal studies has been shown to be similar to thalidomide in action but without the sedative effects or teratogenicity. CC-5013 is currently in phase I and II clinical trials for the treatment of myeloma, some myelodysplastic syndromes, and melanoma. Preliminary results show efficacy with decreased toxicity compared with thalidomide. 

Both cell cultures and animal studies have shown that many of the naturally occurring mono-, sesqui-, di-, sester-, and meroterpenoids as well as retinoids possess potentially chemopreventive activities. Terpenoids are minor but ubiquitous components of our diet, and have the advantage of being non-toxic or relatively non-toxic to humans. More mechanistic-oriented basic research is needed to elucidate the mechanisms of action. Studies of derivatives of these naturally occurring terpenoids are also necessary to elucidate the structure-activity relationship and to guide the development of novel chemopreventive agents. 

Hematological Effects. Both human and animal studies have shown that benzene exerts toxic effects on various parts of the hematological system. All the major types of blood cells are susceptible (erythrocytes, leukocytes, and platelets). In the less severe cases of toxicity, specific deficiencies occur in individual types of blood elements. A more severe effect occurs when there is hypoplasia of the bone marrow, or hypercellular marrow exhibiting ineffective hematopoiesis so that all types of blood cells are found in reduced numbers. This is known as pancytopenia. A biphasic response (i.e., a hyperplastic effect in addition to destruction of the bone marrow cells) has been observed (Aksoy et al. 1972, 1974 Doskin... 

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