Dental care access for low-income and immigrant cancer patients in New York City.

This exploratory study assesses the dental care needs and access of low-income, mostly immigrant cancer patients enrolled in New York City's Integrated Cancer Care Action Network (ICCAN). A nested cohort of patients from ICCAN responded to a dental needs assessment that surveyed current dental health as well as access to, and use of, dental services. 373 patients participated. Self-report of having a dentist to visit, current dental problems, income, and insurance most significantly predicted a dentist visit in the past year. Discussing treatment-related oral side effects with the oncologist greatly increased the likelihood of seeing a dentist, but few patients reported having had this conversation. There is a lack of oral care information flowing from oncologists to low income patients. We found a high number of reported dental problems: concerning because of potential treatment interference and risk for infection. Finally, ability to pay largely determined dental care access in our study participants.

The fatty acid oxidation product 15-A3t-isoprostane is a potent inhibitor of NFκB transcription and macrophage transformation.

Fatty acids such as eicosapentaenoic acid (EPA) have been shown to be beneficial for neurological function and human health. It is widely thought that oxidation products of EPA are responsible for biological activity, although the specific EPA peroxidation product(s) which exert these responses have not yet been identified. In this work we provide the first evidence that the synthesized representative cyclopentenone IsoP, 15-A(3t)-IsoP, serves as a potent inhibitor of lipopolysaccharide-stimulated macrophage activation. The anti-inflammatory activities of 15-A(3t)-IsoP were observed in response not only to lipopolysaccharide, but also to tumor necrosis factor alpha and IL-1b stimulation. Subsequently, this response blocked the ability of these compounds to stimulate nuclear factor kappa b (NFκB) activation and production of proinflammatory cytokines. The bioactivity of 15-A(3t)-IsoP was shown to be dependent upon an unsaturated carbonyl residue which transiently adducts to free thiols. Site directed mutagenesis of the redox sensitive C179 site of the Ikappa kinase beta subunit, blocked the biological activity of 15-A(3t)-IsoP and NFκB activation. The vasoprotective potential of 15-A(3t)-IsoP was underscored by the ability of this compound to block oxidized lipid accumulation, a critical step in foam cell transformation and atherosclerotic plaque formation. Taken together, these are the first data identifying the biological activity of a specific product of EPA peroxidation, which is formed in abundance in vivo. The clear mechanism linking 15-A(3t)-IsoP to redox control of NFκB transcription, and the compound's ability to block foam cell transformation suggest that 15-A(3t)-IsoP provides a unique and potent tool to provide vaso- and cytoprotection under conditions of oxidative stress.

Trans-4-hydroxy-2-hexenal is a neurotoxic product of docosahexaenoic (22:6; n-3) acid oxidation.

Lipid peroxidation of docosahexaenoic (22:6; n-3) acid (DHA) is elevated in the CNS in patients with Alzheimer's disease and in animal models of seizure and ethanol withdrawal. One product of DHA oxidation is trans-4-hydroxy-2-hexenal (HHE), a six carbon analog of the n-6 fatty acid derived trans-4-hydroxy-2-nonenal (HNE). In this work, we studied the neurotoxic potential of HHE. HHE and HNE were toxic to primary cultures of cerebral cortical neurons with LD(50)'s of 23 and 18 micromol/L, respectively. Toxicity was prevented by the addition of thiol scavengers. HHE and HNE depleted neuronal GSH content identically with depletion observed with 10 micromol/L of either compound. Using an antibody raised against HHE-protein adducts, we show that HHE modified specific proteins of 75, 50, and 45 kDa in concentration- and time-dependent manners. The time-dependent formation of HHE differed from that of F4-neuroprostanes following in vitro DHA oxidation likely as a result of the different oxidation pathways involved. Using purified mitochondrial aldehyde dehydrogenase ALDH5A, we found that HHE was oxidized 6.5-fold less efficiently than HNE. Our data demonstrate that HHE and HNE have similarities but also differences in their neurotoxic mechanisms and metabolism.

Increased dietary NaCl induces renal medullary PGE2 production and natriuresis via the EP2 receptor.

A high-NaCl diet induces renal medullary cyclooxygenase (COX)2 expression, and selective intramedullary infusion of a COX2 inhibitor increases blood pressure in rats on a high-salt diet. The present study characterized the specific prostanoid contributing to the antihypertensive effect of COX2. C57BL/6J mice placed on a high-NaCl diet exhibited increased medullary COX2 and microsomal prostaglandin E synthase1 (mPGES1) expression as determined by immunoblot and real-time PCR. Cytosolic prostaglandin E synthase and prostacyclin synthase were not induced by the high-salt diet. Immunofluorescence showed mPGES1 in collecting ducts and interstitial cells. High salt increased renal medullary PGE(2) as determined by gas chromatography/negative ion chemical ionization mass spectrometry. The effect of direct intramedullary PGE(2) infusion was examined in anesthetized uninephrectomized mice. Intramedullary PGE(2) infusion (10 ng/h) increased urine volume (from 3.3 +/- 0.6 to 9.5 +/- 1.6 mul/min) and urine sodium excretion (0.11 +/- 0.02 to 0.32 +/- 0.05 mueq/min). To determine which E-prostanoid (EP) receptor(s) mediated PGE(2)- dependent natriuresis, EP-selective prostanoids were infused. The EP(2) agonist butaprost produced natriuresis (from 0.06 +/- 0.02 to 0.32 +/- 0.05 mueq/min). The natriuretic effect of intramedullary PGE(2) or butaprost was abolished in EP2-deficient mice, which exhibit NaCl-dependent hypertension. In conclusion, a high-salt diet increases renal medullary COX2 and mPGES1 expression, and increases renal medullary PGE(2) synthesis. Renal medullary PGE(2) promotes renal sodium excretion via the EP2 receptor, thereby maintaining normotension in the setting of high salt intake.