Several kinases have been shown to phosphorylate tau protein at Ser-262, an important site involved in the regulation of the binding of tau to microtubules. In this study we compared the phosphorylation of tau at Ser-262 by CaMKII, PhK and PKA in vitro as determined by radioimmunoblots developed by the monoclonal antibody 12E8 which recognizes P-Ser-262 and PSer-356; and Ab-262, a polyclonal antibody which is specific to unphosphorylated Ser-262 in tau. We found that the phosphorylation at Ser-262 was several times more effective by CaMKII than PKA or PhK. Employing rat brain extract as a source of all brain kinases and KN-62, a specific inhibitor of CaMKII, we found that CaMKII accounts for V45% of phosphorylation at Ser-262. Furthermore, in rat brain slices kept metabolically active in oxygenated artificial CSF, phosphorylation of tau at Ser-262 was (i) increased up to 120% in the presence of bradykinin, a CaMKII activator, and (ii) inhibited by V35% in the presence of KN-62. Thus, CaMKII is a major tau Ser-262 kinase in mammalian brain.z 1998 Federation of European Biochemical Societies.

Various doses of amphotericin B encapsulated into unilamellar vesicles of 0.1 ,um diameter (lip-AMB) (1.0 to 20.0 mg/kg of body weight) were compared with free amphotericin B (AMB) (0.5 to 2.0 mg/kg of body weight) in a murine model of disseminated candidiasis. CD2FI mice injected intravenously with 3 x 105 Candida albicans cells were treated with either single-or multiple-dose regimens. Untreated infected mice had a median survival of 7 days, with all mice dead by 12 days. Single doses of AMB resulted in a median survival range from 18 to 23.5 days, with c38% survival by day 42. Single doses of lip-AMB resulted in 88 to 100% survival by day 42. The multiple-dose AMB regimen provided median survival of only 30 to 33 days, with c38% survival by day 42. The multiple-dose lip-AMB regimen resulted in >90% survival by day 42. With single-dose regimens, lip-AMB levels in plasma were severalfold higher than AMB levels in plasma. By 10 h, at equivalent doses, lip-AMB levels in plasma were much higher, whereas AMB levels in plasma were not detectable. Compared with normal values, the blood urea nitrogen, serum glutamic pyruvic transaminase, serum glutamic oxaloacetate transaminase, and serum lactate dehydrogenase levels were not significantly altered by high doses of lip-AMB treatment. Viable C. albicans was recoverable from the kidneys of some of the lip-AMB-treated mice at day 42. Thus, encapsulation into unilamellar liposomes enhances the antifungal efficacy of amphotericin B while reducing the toxicity normally associated with administration of free amphotericin B.

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Hypertension, a major public health problem, becomes more prevalent during aging. Epidemiological studies suggest that environmental factors such as nutrition may play a major role in blood pressure (BP) regulation. It is generally accepted that obesity and sodium/alcohol consumption are important factors, and many believe that calcium, magnesium and potassium consumption are regulatory as well. Less emphasis has been placed on whether macronutrients influence blood pressure significantly. This review focused on the ability of excess calories and consumption of carbohydrates, fats, and proteins to regulate blood pressure.

No abstract