Ca2+-Mg2+ ATPase of mouse cardiac sarcoplasmic reticulum is affected by membrane n-6 and n-3 polyunsaturated fatty acid content

White mice, 18-20 g, were fed purified diets containing two weight percent safflower oil plus ten weight percent menhaden, corn, or olive oil for 2 wk. Menhaden oil ingestion resulted in significantly higher levels of 22:6(n-3) and 20:5(n-3), particularly 22:6(n-3), and lower levels of 20:4(n-6) and 18:2(n-6) in cardiac sarcoplasmic reticulum (SR) phospholipids than did corn or olive oil ingestion. These changes in fatty acid composition resulted in a significant decrease in the value of the n-6/n-3 fatty acid ratio of cardiac SR phospholipids. The ratio was 2.8 versus 0.2 in choline phospholipids and 1.9 versus 0.2 in ethanolamine phospholipids in SR of mice fed corn or menhaden oil, respectively. This reduction in the n-6/n-3 fatty acid ratio was associated with a lower relative activity of Ca2+-Mg2+ ATPase, and a lower initial rate of calcium transport and maximum calcium uptake in SR vesicles from mice fed menhaden oil rather than olive or corn oils. The specific activity of NADPH cytochrome C reductase (EC 1.6.2.3) of cardiac SR was not affected by dietary lipids. These data indicate that modification of SR by 22:6(n-3) may change the SR bilayer structure resulting in alteration of the calcium transport properties of SR vesicles. In addition, our results suggest that reduction of calcium flux across cardiac SR following fish oil consumption may also reduce the susceptibility of myocytes to rapid changes in calcium concentrations which may occur during ischemia and reperfusion.     

Modulation of prostaglandin synthesis in mouse peritoneal macrophages by enrichment of lipids with either eicosapentaenoic or docosahexaenoic acids in vitro

The n-3 polyunsaturated fatty acids (PUFA) of fish oils alter arachidonic acid (AA) metabolism in macrophages. The present investigation studied the efficacy of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), two n-3 PUFA of fish, to alter lipid composition and specific functions of mouse peritoneal macrophages. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were readily incorporated by macrophages in vitro and replaced 25-50% of AA in cellular lipids. The EPA- or DHA-enriched cells synthesized significantly less (50-65%) prostaglandin E2 (PGE2), thromboxane B2 (TXB2) and 6 keto prostaglandin F1(1) alpha (6 keto PGF1 alpha) when stimulated with opsonized zymosan. The enrichment with EPA or DHA did not affect phagocytosis nor superoxide anion formation in macrophages. These studies demonstrated that EPA or DHA can be used to decrease prostaglandin synthesis selectively without affecting the other physiological functions of macrophages.     

The anesthetic management of a patient with paroxysmal nocturnal hemoglobinuria

Implications: This case report describes the anesthetic considerations for a patient with paroxysmal nocturnal hemoglobinuria. Specific strategies to be applied in the perioperative period to prevent hemolytic episodes and venous thrombosis are also discussed.     

Analytical Quality by Design Approach in RP-HPLC Method Development for the Assay of Etofenamate in Dosage Forms

By considering the current regulatory requirement for an analytical method development, a reversed phase high performance liquid chromatographic method for routine analysis of etofenamate in dosage form has been optimized using analytical quality by design approach. Unlike routine approach, the present study was initiated with understanding of quality target product profile, analytical target profile and risk assessment for method variables that affect the method response. A liquid chromatography system equipped with a C₁₈ column (250×4.6 mm, 5 μ), a binary pump and photodiode array detector were used in this work. The experiments were conducted based on plan by central composite design, which could save time, reagents and other resources. Sigma Tech software was used to plan and analyses the experimental observations and obtain quadratic process model. The process model was used for predictive solution for retention time. The predicted data from contour diagram for retention time were verified actually and it satisfied with actual experimental data. The optimized method was achieved at 1.2 ml/min flow rate of using mobile phase composition of methanol and 0.2% triethylamine in water at 85:15, % v/v, pH adjusted to 6.5. The method was validated and verified for targeted method performances, robustness and system suitability during method transfer.