Role of red blood cell deformation in toxicity of contrast media in cerebral angiography

The authors investigated the effect on the brain of red blood cells that had been modified by contrast media. Rat blood was mixed with an equivolume of contrast media, and up to 200 microL of the mixture was infused to the internal carotid artery of the rat. Evans blue was administered intravenously to assess the integrity of the blood-brain barrier (BBB). Immediately after the death of the animal, or 2.5 hours after the infusion, the brain was removed for evaluation of the degree of BBB destruction and edema. Extensive destruction of the BBB, cerebral edema, and death of the animals were induced by infusion of blood mixed with an ionic contrast medium, such as diatrizoate and iothalamate, which deformed red blood cells. Microscopic observation showed atrophy and necrosis of nerve cells and decomposition of nerve fibers in the affected area of the brain. Cerebral damage was not observed in rats injected with blood mixed with a nonionic contrast medium such as iopamidol, iopromide, or metrizamide, which had less effect on red blood cells. Cerebral damage also was observed in the rats injected with blood mixed with a hyperosmotic solution of mannitol, as well as washed red blood cells mixed with an ionic contrast medium. This study's results indicate that hyperosmotic ionic contrast media affect red blood cells and cause disturbance in cerebral circulation.     

Evaluation of diseased coronary arterial branches by polar representations of thallium-201 rotational myocardial imaging

The perfusion territories in polar representations of stress Tl-201 rotational myocardial imaging in patients with angina pectoris who had one diseased coronary segment were analyzed. The lesions proximal or distal to the first major septal perforator in left anterior descending arteries were detected by the presence or absence of defects at the base of the anterior septum. Right coronary artery lesions were detected by the presence of defects at the basal posterior septum, in contrast to the preservation of myocardial uptake at this portion in lesions of the left circumflex artery. The specific defect patterns were detected in cases with lesions at the first diagonal, obtuse marginal, and posterolateral branches. Recognition of these defects in the polar maps allows detailed detection of diseased coronary arterial branches.     

Neuroprotective properties of valproate

Neuropsychiatric disturbances are extremely common in Alzheimer’s disease (AD), and represent integral features of the illness, as well as appropriate targets for therapy. We are interested in designing trials aimed at preventing or delaying the emergence of psychopathology in AD. For symptomatic treatment of agitation, mood stabilizers, particularly sodium valproate, have proved to be beneficial in some patients. Since these effects take several weeks to emerge, we considered that they might be dependent on potentially neuroprotective actions of valproate, such as inhibition of apoptosis and slowing of neurofibrillary tangle formation. In this article we present the rationale for testing the neuroprotective potential of valproate experimentally in mouse models of tauopathy and in a clinical trial of patients with AD who lack psychopathology at baseline. Together, these studies will provide important tests of the hypothesis that valproate, either through inhibition of tau phosphorylation or some other mechanism, is a useful therapeutic agent to modify disease progression in AD.     

Pharmacological properties of fluphenazine-mustard, an irreversible calmodulin antagonist

We describe an improved synthesis and properties of fluphenazine-mustard, a potent phenothiazine having an alkylating chlorethylamine chain in its structure. The drug possesses anticalmodulin activity equivalent to the parent compound, but unlike fluphenazine dihydrochloride, the mustard derivative irreversibly antagonizes the ability of calmodulin to activate cyclic nucleotide phosphodiesterase. This property is partially calcium-dependent and can be overcome by coincubation with excess fluphenazine dihydrochloride. The compound irreversibly inactivated calmodulin when incubated with intact cells and caused single-stranded breakage of DNA. Fluphenazine-mustard possesses potent antiproliferative and cytotoxic properties against malignant cell lines that are likely to be mediated through both of these actions.