Oxidatively modified low density lipoprotein (OM-LDL) is believed to influence the gene expression in macrophage during atherogenesis. We report here that OM-LDL altered the NF-kB activity in RAW264.7 macrophage. Human LDL was oxidized by an azo-initiator, azobis-2-amidinopropane HCI. In the absence of OM-LDL, RAW264.7 macrophage expressed low levels of NFkB (p50/p65) and p50/p50. Lipopolysaccharide (LPS) treatment lead to the high level activation of p50/p65 in macrophage, while the p50/p50 remained unchange. However, by treating macrophage with OM-LDL, p50/p65 was selectively suppressed and p50/p50 was slightly activated. In LPS stimulated macrophage, OM-LDL slightly suppressed the activation of p50/p65 but did not significantly activate p50/p50. Further experiments showed that nitric oxide (NO) production in macrophage was stimulated by LPS. OM-LDL suppressed the NO production caused by LPS. These results indicate that OM-LDL may suppress the expression of NFkB regulated genes such as NO synthetase by the activation of p50/50 homodimer, which may act to suppress transcription factor p50/p65.

We hypothesize that fecal vitamin E may play an important role in preventing colon cancer by inhibiting the generation of mutagens arising from the oxidation of fecal lipids. In this study, male Fischer-344 rats were fed high (HF with 14.5 wt% corn oil and 1 wt% cholesterol) or low fat diets (LF with 5% corn oil) containing alpha-tocopherol (100 lU/kg or 0.156 mmol/kg ), gamma-tocopherol (0.156 mmol/kg) or no tocopherols (-E). The corn oil was tocopherol stripped. We found that rats fed the diets containing RRR-gamma-tocopherol had dramatically higher fecal levels of tocopherol than rats fed the corresponding diets containing the same level (on a mmol/kg basis) of RRR-alpha-tocopherol. Moreover, rats fed the HF diets had higher levels of fecal tocopherol levels than did rats fed the LF diets. These data may help explain the epidemioîogical evidence suggesting that consumption of vegetable fat, unlike animal fat, is not associated with an increased risk of colon cancer. Vegetable fat, unlike animal fat, has a high content of gamma-tocopherol. This research was support by a grant from Eastman Chemical Co.

Dietary levels of polyunsaturated fat (PUFA) and vitamin E may modulate oxidative damage to cardiac tissue caused by ischemia-reperfusion. In this study, rats were fed corn oïl (CO) diets either deficient (CO-E) or supplemented (CO+E) with RRR-α-tocopherol (TOC) or butter oil (BO) diets either deficient (BO-E) or supplemented (BO + E) with TOC. CO oil has a higher PUFA than BO. PUFAs are very susceptible to lipid peroxidation. Intact hearts were isolated and subjected to in vitro global ischemia-reperfusion. TOC levels in cardiac tissue from rats fed the CO-f AE and BO+AE diets were 17.6 ±_ 1.6 ng/mg and 23.3 ±_ 2.2 ng/mg, respectively but were undetectable in rats fed the CO-AE and BO-AE diets. PUFAs were higher in cardiac tissue from rats fed the CO + AE and CO-AE diets (51.0% ±1.06% and 52.6% ± 1.61%) than in cardiac tissue from rats fed the BO + AE and BO-AE diets (40.0% ±3.41% and 39.0% ±3.41%). Two way ANOVA with dietary TOC level (±E) and fat type (CO or BO) as factors indicated that rats fed the TOC supplemented diets (CO + AE and BO + AE) had a better recovery of aortic output after ischemia reperfusion than did heart from rats fed the TOC deficient diets (CO-AE and BO-AE). The recovery of systolic pressure in rats fed the BO diets was better than in rats fed the CO diets (p<0.05). These data suggest that diets low in PUFAs and/or supplemented with TOC may help prevent oxidative damage caused by ischemia-reperfusion.

Little is know about the effect of inhalation of methanol and other solvents on the pregnancy and the growth of the fetus. We report a preterm male infant who developed cerebral infarcts in utero, leading to large areas of bilateral frontal cortical leukomalacia following chronic maternal inhalation of carburetor-cleaning fluid during pregnancy. The infant presented with acute fetal distress with significant metabolic acidosis at birth. Initial hypotonia was followed by generalized hypertonicity. This infant did not exhibit typical facial features of fetal alcoholic syndrome.

Patients with HIV infection represent one of the most rapidly developing groups with cardiovascular disease. Since patients infected with the HIV virus are living longer, cardiovascular complications are now becoming more obvious. Moreover, cocaine, a common drug of abuse, is also associated with a variety of cardiovascular disorders and may be an additional comorbid factor in these patients. Myocarditis, cardiomyopathy, hypertensive crises, atherosclerosis, and endocarditis occur with increased frequency in these patients. Patients with HIV and heart disease are a subset of patients that tend to die earlier and respond adversely to drugs commonly used to treat heart disease. Further clinical and basic studies are required to understand the pathogenesis and management of these patients.

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Chronic Granulomatous Disease is the most commonly encountered immunodeficiency involving the phagocyte, and is characterized by repeated infections with bacterial and fungal pathogens, as well as the formation of granulomas in tissue. The disease is the result of a disorder of the NADPH oxidase system, culminating in an inability of the phagocyte to generate superoxide, leading to the defective killing of pathogenic organisms. This can lead to infections with Staphylococcus aureus, Psedomonas species, Nocardia species, and fungi (such as Aspergillus species and Candida albicans). Involvement of vital or large organs can contribute to morbidity and/or mortality in the affected patients. Major advances have occurred in the diagnosis and treatment of this disease, with the potential for gene therapy or stem cell transplantation looming on the horizon.

No description available.