Reverse redistribution on dynamic exercise and dipyridamole stress technetium-99m-MIBI myocardial SPECT.

Reverse redistribution on 201TI-chloride stress-redistribution myocardial scintigraphy has been associated with coronary artery stenosis. We report a patient whose two separate 99mTc-MIBI myocardial SPECT stress studies (dynamic exercise and dipyridamole) showed septal reverse redistribution and fixed inferior defect. Echocardiograms showed left ventricular (LV) hypertrophy and diffuse hypokinesis, especially in the inferior wall, and EKG showed LV hypertrophy and strain and inferior infarct. Coronary angiogram confirmed two-vessel disease involving 80%-90% stenosis of the proximal second diagonal branch of the left anterior descending artery and 75%-90% stenosis of the right coronary artery as well as global left ventricular dysfunction. Reverse redistribution on 99mTc-MIBI myocardial SPECT occurring on dynamic or dipyridamole stress may indicate damaged but viable myocardium.

The effect of mercury chloride and methyl mercury on brain microsomal Na+-K+-ATPase after partial delipidisation with Lubrol.

The microsomal Na+-K+-ATPase of rat brain was inhibited by mercury chloride and methyl mercury. The IC50 was 6.5 X 10(-7) M for mercury chloride and 3.5 X 10(-6) M for methyl mercury. The inhibition was of a non-competitive type with respect to ATP. The non-ionic detergent Lubrol potentiated the inhibitory effect of both mercurials. It is concluded that Lubrol removes the bulk lipids present outside the catalytic center of the enzyme. Consequently, the enzyme will become more sensitive to the inhibition by both mercurials.

Studies on the inhibition of brain synaptosomal Na+/K+-ATPase by mercury chloride and methyl mercury chloride.

The effect of mercury chloride (HgCl2) and methyl mercury chloride (MeHg) on brain synaptosomal Na+/K+-ATPase was determined in vitro. It was shown that HgCl2 is a more powerful inhibitor than MeHg. The IC50 were 5 X 10(-7) M for HgCl2 and 2.3 X 10(-6) M for MeHg. A non-competitive type of inhibition was observed with the two mercurials. Removal of contaminating lipids with the non-ionic detergent Lubrol did not affect the inhibition of either mercurial. It is concluded that non-essential lipids do not play a significant role in the inhibitory effect of MeHg and that the potency of these mercurials on to inhibit brain synaptosomal Na+/K+-ATPase largely depends on their capacity to block sulfhydryl groups.

Effect of lindane on synaptosomal Na+/K+-ATPase in relation to its subcellular distribution in the brain.

Mouse brain synaptosomal Na+/K+-ATPase was inhibited by 23%, 18 hrs after a single intraperitoneal dose of 40 mg lindane (dissolved in olive oil) per kg. The inhibition was of a non-competitive type with respect to ATP. Pretreatment with lindane also potentiated the inhibitory effect of ethanol on this enzyme. It is suggested to consider this interaction at the synaptosomal level when evaluating the anaesthetic effect of ethanol in contaminated persons. Although the synaptosomal Na+/K+-ATPase was inhibited after pretreatment with lindane in vivo, neither lindane nor its metabolites were present in the synaptosomal fraction when determining the subcellular distribution of U-[14C]-lindane in the brain. These results raise some questions regarding the current opinion that lindane exerts some of its central effects through binding to the synaptosomal membrane.

Effect of daily oral intake of manganese on free polysomal protein synthesis of rat brain.

The effect of manganese on free polysomal protein synthesis of immature rat brain (3 weeks old) has been determined after 1, 2, 3, and 4 weeks of daily intake of 55 micrograms manganese/ml of drinking water. The protein synthesis was inhibited up to 35% during the first 3 weeks and returned toward the control level during the fourth week of treatment. Cross-incubation experiments with polysomes and pH 5 enzyme fractions indicated that the inhibition of protein synthesis is due to alteration of the pH 5 enzyme fraction. Furthermore, cerebral t-RNA content was reduced by 20% during the first 3 weeks and also returned to the control level after 4 weeks. The data suggest that the previously reported retardation in learning and memory of manganese treated immature rats may partly be due to alteration of cerebral RNA and protein synthesis. It was also evident that an adaptation mechanism to the observed effect of manganese developes after three weeks of daily intake of 55 micrograms manganese/ml.

Effect of cadmium and copper on monoamine oxidase type A and B in brain and liver mitochondria.

The effect of cadmium and copper on monoamine oxidase type A and B in mitochondrial preparations from brain and liver was determined in vitro. The results showed a dose-related inhibition of the enzyme. Both the A and B forms of the enzyme were similarly inhibited by the presence of either cadmium or copper. Copper has been shown to be a 7-8 times more potent inhibitor of monoamine oxidase than cadmium. The data suggest that the intracellular concentration of unbound copper (13 mumol/l) or cadmium (100 mumol/l) may inhibit monoamine oxidase in brain and liver by 50%.

Is tolerance to delta-9-THC cellular or metabolic? The subcellular distribution of delta-9-tetrahydrocannabinol and its metabolites in brains of tolerant and non-tolerant rats.

Rats were injected intraperitoneally once every 12 h with 10 mg/kg delta-9-THC and the time course of the depressant effect was determined after one and nine injections. The motor activity of naive rats was maximally depressed between 1 and 4 h and returned to control levels 8 h after treatment. After nine injections, the maximum intensity of the depressant effect was not different from that after one injection but had completely disappeared at an earlier time point (4 h p.i.) indicating the development of tolerance to the duration of effect on motor activity. The subcellular distribution studies in brains of tolerant and non-tolerant rats indicated that an accelerated shift in the concentrations of delta-9-THC and 11-OH-delta-9-THC towards highly polar metabolites in the brains, rather than an increased elimination of these cannabinoids or decreased sensitivity of the brain may be responsible for the development of tolerance to delta-9-THC.

An attempt to correlate the development of tolerance to delta-9-tetrahydrocannabinol and d-amphetamine with their subcellular distribution in rat brain.

The daily application in rats of d-amphetamine during 4 weeks in increasing doses from 16-80 mg/kg/day developed a tolerance. The quantitative evaluation of the relative accumulation of unchanged d-amphetamine in different subcellular brain fractions estimated with 3H labelled d-amphetamine showed that the development of tolerance to amphetamine is not associated with a decreased accumulation of the unchanged drug in any subcellular fraction of the brain. Synthetic delta-9-tetrahydrocannabinol (THC) was injected (10 mg/kg) to rats twice daily. After the 9th injection the intensity of the initial depressant effect was approximately similar to that after one injection but completely disappeared after 3 hrs of treatment. The specific activities of delta-9-THC and its metabolites in brain subcellular fractions were estimated with use of 3H-delta-9-THC. The tolerance to delta-9-THC in contrast to amphetamine seems to be mainly metabolic.

The effect of chronic self-administration of d-amphetamine on food intake, locomotor activity, and C14-leucine incorporation into cerebral cortex protein.

Rats had free access to 0.02% d-amphetamine solution instead of water for 23 days. The daily amphetamine consumption was found to increase from 16 mg/kg on day 1 up to 47 mg/kg on day 23. Tolerance to the anorexic effect of the drug was apparent on day 11. The initial depression in body weight persisted throughout the experiment. The hyperactivity of rats remained at the same level despite the daily increase in amphetamine intake. The incorporation of C14-leucine into cerebral cortex proteins was initially increased and returned to control level after 2 weeks of treatment. No direct correlation between hyperactivity and brain cortex protein synthesis was observed.