Cannabidiol and (-)Delta9-tetrahydrocannabinol are neuroprotective antioxidants

The neuroprotective actions of cannabidiol and other cannabinoids were examined in rat cortical neuron cultures exposed to toxic levels of the excitatory neurotransmitter glutamate. Glutamate toxicity was reduced by both cannabidiol, a nonpsychoactive constituent of marijuana, and the psychotropic cannabinoid (-)Delta9-tetrahydrocannabinol (THC). Cannabinoids protected equally well against neurotoxicity mediated by N-methyl-D-aspartate receptors, 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid receptors, or kainate receptors. N-methyl-D-aspartate receptor-induced toxicity has been shown to be calcium dependent; this study demonstrates that 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid/kainate receptor-type neurotoxicity is also calcium-dependent, partly mediated by voltage sensitive calcium channels. The neuroprotection observed with cannabidiol and THC was unaffected by cannabinoid receptor antagonist, indicating it to be cannabinoid receptor independent. Previous studies have shown that glutamate toxicity may be prevented by antioxidants. Cannabidiol, THC and several synthetic cannabinoids all were demonstrated to be antioxidants by cyclic voltametry. Cannabidiol and THC also were shown to prevent hydroperoxide-induced oxidative damage as well as or better than other antioxidants in a chemical (Fenton reaction) system and neuronal cultures. Cannabidiol was more protective against glutamate neurotoxicity than either ascorbate or alpha-tocopherol, indicating it to be a potent antioxidant. These data also suggest that the naturally occurring, nonpsychotropic cannabinoid, cannabidiol, may be a potentially useful therapeutic agent for the treatment of oxidative neurological disorders such as cerebral ischemia.     

Use of 2-[18F]fluoro-2-deoxyglucose as a potential agent in the prediction of graft rejection by positron emission tomography

BACKGROUND: We investigated the potential of predicting allograft rejection by measuring the ability of graft-infiltrating cells to take up 2-[18F]fluoro-2-deoxyglucose ([18F]FDG). This molecule is a positron emitting glucose analogue that is taken up by metabolically active cells and can be detected using positron emission tomography. METHODS: Uptake of [18F]FDG during an alloresponse was measured both in vitro in mixed lymphocyte cultures and in vivo using allogeneic and syngeneic skin grafts. RESULTS: Uptake of [18F]FDG was seen in a mixed lymphocyte reaction. Using a mouse skin graft model, we found that mean [18F]FDG uptake was 1.5-2 times higher in allografts than in syngeneic grafts; the increase in uptake correlated with the level of T-cell infiltrate seen histologically. CONCLUSION: Assessing the metabolic activity of graft-infiltrating cells with [18F]FDG may be useful in the prediction of graft rejection episodes.     

Excretion of a radiolabelled anticancer biodegradable polymeric implant from the rabbit brain

The elimination of a clinically used anticancer biodegradable polymer implant (Gliadel) in the rabbit brain was studied. The implant is composed of N,N-bis(2-chloroethyl)-N-nitrosourea (BCNU) (1.6 wt%) dispersed in a copolyanhydride matrix of 1,3-bis(p-carboxyphenoxypropane) (CPP) and sebacic acid (SA) in a 20:80 molar ratio. Four groups of rabbits were implanted with wafers loaded with BCNU, one in a 14C-SA-labelled polymer, another in a 14C-CPP-labelled polymer and two groups with 14C-BCNU in a non-labelled polymer, one for BCNU disposition study and one for residual drug study. In the rabbits implanted with the 14C-SA-labelled polymer, approximately 10% of the radioactivity was found in the urine and 2% in the faeces, and about 10% remained in the device 7 d after implantation. In contrast, only 4% of the radioactivity of the 14C-CPP-labelled polymer was found in urine and faeces during this period. However, a drastic increase in the CPP excretion was found after 9 d, and at 21 d, 64% of the implanted 14C-CPP was found in the urine and faeces, and 29% was still in the recovered wafers. Approximately 50% of the BCNU in the wafers was released in 3 d, and over 95% was released after 6 d in the rabbit brain. This study demonstrates that BCNU-loaded polyanhydride is biodegradable and is excreted from the body primarily through the renal system. The water-soluble components SA and BCNU were rapidly excreted, while the insoluble CPP was gradually eliminated after a lag time of 9 d.     

All-trans beta-carotene is absorbed preferentially to 9-cis beta-carotene, but the latter accumulates in the tissues of domestic ferrets (Mustela putorius puro)

The algae Dunaliella bardawil and Dunaliella salina naturally contain large concentrations of all-trans and 9-cis beta-carotene (betaC). The purpose of this study was to compare the relative serum and tissue accumulation of all-trans and 9-cis betaC in ferrets fed different ratios of all-trans/9-cis betaC derived from two commercial sources, D. bardawil or D. salina (Betatene). Male ferrets (7 wk old) were fed carotene-free, pelleted diets for 27 d. Beginning on d 18, groups of ferrets (n = 6 or 7) received daily, one of six oral supplements varying in ratios of 9-cis and all-trans betaC mixed with approximately 1.0mL of Ensure. Four supplements containing 5.2-8.3 micromol total betaC were prepared from a 20% Betatene preparation, D. bardawil, a high-cis Betatene preparation, and Betatene further enriched in 9-cis betaC with all-trans betaC/9-cis betaC ratios of 2.2, 1.5, 0.6 and 0.4, respectively. Two control supplements, high and low betaC, were prepared from commercial betaC beadlets. The high control supplement had an all-trans/9-cis ratio of 19.0, whereas 9-cis betaC was not detected in the low supplement. On d 27, serum and tissues were obtained for HPLC analysis of betaC and its isomers. Analysis of livers showed that all-trans betaC was the primary isomer present, but 9-cis and other isomers were also detected in all groups. The hepatic all-trans/9-cis ratios were 5.9, 4.9, 2.5, 1.4, 52.2 and47.5, respectively, for the groups listed above. Lower amounts of all-trans and 9-cis betaC were found in kidneys compared with the liver, but ratios of all-trans/9-cis were not different among groups. Only trace amounts of 9-cis betaC were found in serum. These results demonstrate that the algae D. bardawil and D. salina provide a bioavailable source of betaC isomers, but, as in humans, absorption of 9-cis betaC is poor and any 9-cis betaC absorbed is apparently cleared by the liver.     

Microstructural changes during ageing of Cu-2.5 wt% Ti

Microstructural changes in Cu-2.5wt % Ti during ageing at 573 and 773 K have been studied by transmission electron microscopy. Ageing times ranged from 60 sec to 200 h. Ordering of the precipitates was observed after very short ageing treatments at 773 K, and coarsening according tot ^1/3 was also observed from very early times. The particles were observed to become increasingly aligned into rod-like groups along 10 0 as ageing progressed. These results permit a new interpretation of the strengthening mechanisms in this alloy.     

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An experimental study of plasticating in a reciprocating-screw injection molding machine

Experimental studies were performed with low density polyethylene, acrylonitrile-butadiene-styrene polymers and on polyvinyl chloride to elucidate the nature of the plasticating process in a reciprocating-screw injection molding machine. Melting data, obtained by use of the “cooling experiment,” and plastic temperature data reveal that the screw recharge process is a transient plasticating extrusion process which gradually approaches the equilibrium extrusion behavior as the screw rotates. If the screw rotation time is a high percentage of the total cycle time, the plasticating behavior is very similar to steady-state extrusion behavior, but if the screw rotation time is a small percentage of the total cycle time, the plasticating behavior is significantly different. Furthermore, better plasticating is obtained by use of a low RPM and high percentage rotation time than by a high RPM and low percentage rotation time.