Toxic lipid

However, peroxidation can also occur in extracellular lipid transport proteins, such as low-density lipoprotein (LDL), that are protected from oxidation only by antioxidants present in the lipoprotein itself or the exttacellular environment of the artery wall. It appeats that these antioxidants are not always adequate to protect LDL from oxidation in vivo, and extensive lipid peroxidation can occur in the artery wall and contribute to the pathogenesis of atherosclerosis (Palinski et al., 1989 Ester-bauer et al., 1990, 1993 Yla-Herttuala et al., 1990 Salonen et al., 1992). Once initiation occurs the formation of the peroxyl radical results in a chain reaction, which, in effect, greatly amplifies the severity of the initial oxidative insult. In this situation it is likely that the peroxidation reaction can proceed unchecked resulting in the formation of toxic lipid decomposition products such as aldehydes and the F2 isoprostanes (Esterbauer et al., 1991 Morrow et al., 1990). In support of this hypothesis, cytotoxic aldehydes such as 4-... 

Decadienal has been reported as one of the most toxic lipid hydroperoxide breakdown products to ceUs . Besides l,Ai -etheno-2 -deoxyadenosine (edAdo) (156)... 

When purified endotoxin was treated with 0.1 N HC1 for 30 min at 100 °C, the resulting nondialyzable residue was also free of KDO but was nontoxic (CELD50, >10 yg) and nonpyrogenic (FI401 20 yg) (Table IV). We have designated this product nontoxic lipid A (Detox) and demonstrated its low toxicity in four animal species (Table II). The nontoxic lipid A in combination with P3 and ACP (or CWS) retained a degree of tumor regressive potency (80% cures) similar to that observed with the toxic lipid A (88% cures) and the purified endoxtoxin (81% cures). 

Results of chemical analysis showed that the glucosamine and total fatty acid contents of the KDO depleted, toxic lipid A and the nontoxic lipid A were essentially the same but that the nontoxic lipid A was significantly lower in the phosphorus content (Table V). The molar ratio of glucosamine phosphorus fatty acids was 2 2 4 for the toxic lipid A and 2 1 4 for the nontoxic lipid A. The relative molar distribution of normal fatty acids (lauric, myristic, and palmitic acids) and the 3-hydroxymyristic acid did not indicate a correlation between the content of these components and toxicity. The nontoxic lipid A possessed as high a tumor regression activity when combined with CWS as did the purified... 

Qureshi, N., Takayama, K., Ribi, E. Purification and structural determination of non-toxic lipid-A from lipopolysaccharide of Salmonella typhimurium. J Biol Chem 257 (1982) 11808-11815. Raetz, C.R., Whitfield, C. Lipopolysaccharide endotoxins. Annu Rev Biochem 71 (2002) 635-700. Reed, S.G., Bertholet, S., Coler, R.N., Friede, M. New horizons in adjuvants for vaccine development. Trends Immunol 30 (2009) 23-32. 

B31. Bruns, C. M., Hubatsch, I., Ridderstrom, M., Mannervik, B., and Tainer, J. A., Human glutathione transferase A4-4 crystal structures and mutagenesis reveal the basis of high catalytic efficiency with toxic lipid peroxidation products. J. Mol. Biol. 288, 427 139 (1999). 

A characteristic of lipid products, particularly those with unsaturated lipids is peroxide formation with oxi-dation. Free radicals such as ROO, RO, and OH can damage the drug and induce toxicity. Lipid peroxides may also form due to autoxidation, which increases with unsaturation level. Hydrolysis of the... 

A toxic lipid isolated by Spitznagel and Dubos by extraction of Mycobacteria with monochlorobenzene has been shown to contain cord factor as the only active compound. ... 

The chemistry of cord factor, a toxic lipid of virulent or attenuated Mycobacteria has already been described in detail (see p. 210). It has also been mentioned that at least part of this biological activity can be explained by the action of cord factor on dehydrogenases dependent on diphospho-pyridine nucleotide as described by Kato and coworkers (see p. 231). 

Came and coworkers have described a toxic lipid extracted from Coryne-bacterium ovis, a pathogen which, in sheep, causes a wide-spread disease known as caseous lymphadenitis. The lipid extracted from living C. ovis with petroleum ether is toxic for leucocytes in vitro. A preliminary chemical investigation of this lipid fraction, kindly prepared by Dr. Came, has not yet yielded definite information about the chemical nature of the active fraction. A synthetic 6,6 -dicorynomycolate of trehalose, prepared by Diara and Pudles, has been found devoid of leucotoxic action. 

Dimond EG, Caravaca J, Benchimol A. 1963. Vanadium Excretion, toxicity, lipid effect in man. Am J Clin Nutr 12 49-53. 

Amphotericin B combined with flucytosine is the initial treatment of choice. In patients who cannot tolerate flucytosine, amphotericin B alone is an acceptable altemative. After the initially successful 2-week iuductiou period, cousohdatiou therapy with flucouazole cau be adruinistered for 8 weeks or uutil CSF cultures are negative. In patients in whom fluconazole cannot be given, itraconazole is an acceptable, albeit less effective, alternative. Combination therapy with fluconazole plus flucytosiue is effective however, it is recommeuded as au altemative to the precediug therapies because of its poteutial for toxicity. Lipid... 

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