These results suggest that these epoxygenase-related SNP are not associated with increased risk of hypertension in the African American population. There was significant linkage disequilibrium between CYP2C8*3 and CYP2C9*2 alleles that was not associated with hypertension.

Abstract-Increased dietary linoleic acid has been associated with reduced blood pressure in clinical and animal studies possibly mediated by prostaglandins. Urinary linoleate and prostaglandin metabolite excretion were investigated in subjects exposed to a salt-loading/salt-depletion regimen. Twelve healthy subjects were recruited from the New Orleans population (before Hurricaine Katrina) and admitted to the Tulane-Louisiana State University-Charity Hospital General Clinical Research Center after a 5-day outpatient lead-in phase on a 160-mmol sodium diet. On inpatient day 1, the subjects were maintained on the 160-mmol sodium diet, and a 24-hour urine specimen was collected. On day 2, the subjects received 2 L of IV normal saline over 4 hours and continued on a 160-mmol Na ϩ diet (total: 460 mmol of sodium). Two 12-hour urine collections were obtained. On day 3, the subjects received three 40-mg oral doses of furosemide, two 12-hour urine collections were obtained, and the subjects were given a 10-mmol sodium diet. Urinary oxidized lipids were measured by high-performance liquid chromatography-tandem quadrupole mass spectroscopy. The excretion of the urinary linoleate metabolites, dihydroxyoctadecamonoenoic acids, and trihydroxyoctadecamonoenoic acids increased significantly during intravenous salt loading as compared with day 1 and the salt-depleted periods. The urinary excretion of 6-keto-prostaglandin F1␣ was unaffected by salt loading but was dramatically increased 7-to 10-fold by salt depletion. Prostaglandin E2 excretion was positively correlated with sodium excretion. The saltstimulated production of linoleic acid diols and triols may inhibit tubular sodium reabsorption, thereby assisting in the excretion of the sodium load. T he dietary intake of linoleic acid (LA), an essential fatty acid, influences blood pressure. Increased dietary LA intake reduces systolic blood pressure, increases red blood cell membrane LA content, and alters red and white blood cell sodium transport processes in clinical studies. 1-7 Conversely, dietary LA deprivation in rats results in the development of salt-sensitive hypertension and an inability to excrete an acute salt load, with both effects reversed by the administration of LA. 8 -10 LA is a precursor of arachidonic acid, and it has been proposed that the effects of LA on blood pressure and salt excretion may be mediated through the production of various cytochrome P450 (CYP) eicosanoids and/or prostaglandins, including the epoxyeicosatrienoic acids (EETs) [11][12][13][14] and the prostacyclin metabolite 6-keto-prostaglandin (PG) F1␣. 15,16 Inhibition of CYP-mediated EET production has been associated with the development of hypertension in rats. 11 Dietary salt loading upregulates CYP2C23 in rats, increasing EET production and inhibiting Na ϩ reabsorption, whereas low-salt diets suppress this enzyme. 12,14 The EETs have also been shown to directly inhibit the distal tubule epithelial sodium channel. 13,14 LA, however, also serves as a substrate in various oxygenation r...

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The survival of tumor cells at 1,4, and 24 h after single, double, and triple freezing and thawing cycles has been examined. After freezing two xenografted tumors of human origin (GW-77 and GW-127) in the cheek pouch of unconditioned Syrian hamsters with liquid nitrogen under pressure (––196°C), it was found that retransplantation of the cryogenic tumors at 1 h post single freezing and thawing resulted in tumor growth. Intact tumor cells could also be demonstrated microscopically at this time. No viable tumor cells could be found at 4 h or later post single freezing and thawing, or at 1 h or later after multiple freezing and thawing cycles. The role of the cryogenic environment on the survival of viable tumor cells within the frozen lesion, as well as the importance of multiple rapid freezing and slow thawing cycles, followed by a period of delay prior to excision of the frozen tumor, have been stressed.