Low-dose dietary supplementation with omega-3 fish oils in systemic lupus erythematosus not only has a therapeutic effect on disease activity but also improves endothelial function and reduces oxidative stress and may therefore confer cardiovascular benefits.

Background-Impaired endothelium-mediated vasodilatation (EMVD) in congestive cardiac failure (CCF) has been linked to decreased nitric oxide (NO) bioavailability because of its interaction with vascular superoxide (O 2 ·Ϫ ), derived predominantly from NAD(P)H-dependent oxidases. When uncoupled from essential cofactors, endothelial nitric oxide synthase (eNOS) produces O 2 ·Ϫ . We studied the functional consequences of eNOS uncoupling in relation to EMVD in patients with CCF. Methods and Results-We employed the platelet as a compartmentalized ex-vivo model to examine O 2 ·Ϫ and NO production. When eNOS is functioning normally, incorporation of N -Nitro-L-Arginine methyl ester (L-NAME, 1 mmol/L), results in increased O 2 ·Ϫ detection, as inhibition of NO production prevents NO scavenging of O 2 ·Ϫ . This was observed in controls and 9 of the CCF patients, in whom O 2 ·Ϫ detection increased by 63% and 101%, respectively. In the remaining 9 CCF patients, incorporation of L-NAME reduced O 2 ·Ϫ production by 39%, indicating O 2 ·Ϫ production by eNOS uncoupling. Detection of platelet-derived NO was significantly greater in eNOS-coupled platelets compared with the uncoupled group (2.8Ϯ1.4 versus 0.9Ϯ0.4 pmol/10 8 platelets, Pϭ0.04). Endothelium-dependent and -independent vasodilator responses to acetylcholine and sodium nitroprusside recorded using venous occlusion plethysmography were significantly impaired in patients exhibiting eNOS uncoupling. Conclusions-This study provides first evidence that platelet eNOS can become uncoupled in human CCF. Impaired endothelium-dependent and -independent vasodilator responses and diminished platelet-derived NO production occurred in association with enzyme uncoupling.

The pharmacokinetics of a novel praziquantel preparation (Distocide) were investigated in Sudanese patients with hepatosplenic schistosomiasis and in healthy volunteers, and compared with those of Biltricide. The results of the first study indicated greater (P less than 0.05) plasma concentrations of Biltricide at 1.5, 2, 3 and 5 h after administration than with Distocide; plasma elimination half-lives (t 1/2) were not significantly different. In patients with hepatosplenic schistosomiasis, higher plasma levels of Distocide were noted (P less than 0.05 at 8 h) compared to healthy controls; however, due to wide inter-individual variations, there were no significant differences in maximum plasma concentration, time to maximum plasma concentration, area under the plasma concentration curve (AUC), volume of distribution, or clearance; t 1/2 was greater (P less than 0.05) in patients (11.9 +/- 5.4 h) than controls (2.3 +/- 0.4 h). In the presence of food, higher plasma concentrations of Distocide occurred compared to the fasting state; AUCs were greater (P less than 0.01) in both food groups, although the values of t 1/2 were shorter. The lower plasma levels and longer duration of action of Distocide may be advantageous in reducing side effects and prolonging exposure of the schistosomes to the drug.

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Objective-Impaired flow-mediated dilation (FMD) occurs in disease states associated with atherosclerosis, including SLE.The primary hemodynamic determinant of FMD is wall shear stress, which is critically dependent on the forearm microcirculation. We explored the relationship between FMD, diastolic shear stress (DSS), and the forearm microcirculation in 32 patients with SLE and 19 controls. Methods and Results-DSS was calculated using (mean diastolic velocityϫ8ϫblood viscosity)/baseline brachial artery diameter. Doppler velocity envelopes from the first 15 seconds of reactive hyperemia were analyzed for resistive index (RI), and interrogated in the frequency domain to assess forearm microvascular hemodynamics. FMD was significantly impaired in SLE patients (median, 2.4%; range, Ϫ2.1% to 10.7% versus median 5.8%; range, 1.9% to 14%; PϽ0.001). DSS (dyne/cm 2 ) was significantly reduced in SLE patients (median, 18.5; range, 3.9 to 34.0 versus median 21.8; range, 14.1 to 58.7; Pϭ0.037). A strong correlation between FMD and DSS, r s ϭ0.65, Pϭ0.01 was found. Postischemic RI was not significantly different between the 2 groups; however, there were significant differences in the power-frequency spectrums of the Doppler velocity envelopes (PϽ0.05). Conclusions-These data suggest that in SLE, altered structure and function of the forearm microcirculation contributes to impaired FMD through a reduction in shear stress stimulus. Key Words: eigenvector Ⅲ flow-mediated dilation Ⅲ microcirculation Ⅲ shear stress Ⅲ systemic lupus erythematosus S ystemic lupus erythematosus (SLE) is the archetypal autoimmune disease, with a wide range of clinical manifestations. Among the clinical challenges of SLE, one of the most compelling is the high incidence of atherosclerosis in young women. In 1976, Urowitz et al showed a bimodal mortality pattern in SLE, with late deaths (comprising 45%) attributed to myocardial infarction. 1 Women with SLE have a high prevalence of coronary artery disease (CAD) 2 and an incidence of myocardial infarction up to 50 times higher than age-matched normals. 3 Classical risk factors are similar to those in the general population, 3 but the increased risk of atherosclerosis is not exclusively related to traditional Framingham risk factors alone, 4 with a recent report highlighting SLE itself as an independent risk. 5 Whereas several studies have highlighted the presence of subclinical atherosclerosis in SLE, 6,7 the pathogenesis is not fully understood. It has been proposed that autoimmune vascular injury in SLE may predispose to atherosclerotic plaque formation through mechanisms that promote endothelial dysfunction, the earliest precursor for plaque development. 8 -10 Flow-mediated dilation of the brachial artery (FMD) is used clinically as an indirect bioassay for endotheliumderived nitric oxide (NO) production. The primary hemodynamic determinant of FMD is wall shear stress, 11-13 and the degree of FMD has been shown to be proportional to both systolic and diastolic shear stress (DSS) in response to incr...