A new perspective on cannabinoid signalling: complementary localization of fatty acid amide hydrolase and the CB1 receptor in rat brain

CB1-type cannabinoid receptors in the brain mediate effects of the drug cannabis. Anandamide and sn-2 arachidonylglycerol (2-AG) are putative endogenous ligands for CB1 receptors, but it is not known which cells in the brain produce these molecules. Recently, an enzyme which catalyses hydrolysis of anandamide and 2-AG, known as fatty acid amide hydrolase (FAAH), was identified in mammals. Here we have analysed the distribution of FAAH in rat brain and compared its cellular localization with CB1-type cannabinoid receptors using immunocytochemistry. High concentrations of FAAH activity were detected in the cerebellum, hippocampus and neocortex, regions of the rat brain which are enriched with cannabinoid receptors. Immunocytochemical analysis of these brain regions revealed a complementary pattern of FAAH and CB1 expression with CB1 immunoreactivity occurring in fibres surrounding FAAH-immunoreactive cell bodies and/or dendrites. In the cerebellum, FAAH was expressed in the cell bodies of Purkinje cells and CB1 was expressed in the axons of granule cells and basket cells, neurons which are presynaptic to Purkinje cells. The close correspondence in the distribution of FAAH and CB1 in rat brain and the complementary pattern of FAAH and CB1 expression at the cellular level provides important new evidence that FAAH may participate in cannabinoid signalling mechanisms of the brain.     

Alcoholic beverage preference and risks of alcohol-related medical consequences: a preliminary report from the National Longitudinal Alcohol Epidemiologic Survey

In studying the alcohol-morbidity association, a substantial amount of attention and efforts has been focused on volume of alcohol intake. Considerably less is known about the differential health effects of beverage types. The present study used a most recent national household survey of the U.S. general population on drinking practices, alcohol use disorders, and their associated disabilities. The prevalence of a broad range of alcohol-related diseases was examined with respect to preferred beverage type, as well as consumption level. Our findings showed a reduced health risk associated with beer and wine drinking for a number of physical disorders, and a somewhat favorable cardiovascular effect of these two beverage types in relation to abstention. Among preferrers of beer, wine, and liquor, the results indicate that liquor preference is associated with elevated morbidity for several medical consequences. However, interpretation of results and the public health implications of these findings need to be taken cautiously, because sociodemographic and other behavioral characteristics were not considered in this preliminary report.     

Fractography as well as fatigue and fracture of 25 wt% silicon carbide whisker reinforced alumina ceramic composite

Fatigue cracked and fast fractured regions in four-point bend specimens prepared from 25 wt% silicon carbide whisker reinforced alumina composite were examined by scanning electron microscopy. This composite was found to be susceptible to a fatigue crack growth phenomenon similar to that in the case of metallic materials, but with a higher crack growth exponent. In the fatigue region, the alumina matrix failed mainly in a transgranular mode and the whiskers mainly failed with a flat fracture surface but without their pullout. On the other hand, in the fast fracture region, the whiskers failed predominantly by pullout and the alumina matrix failed in a mixed mode with about half in transgranular and the other half in intergranular mode. Thus, to improve the fracture toughness of the material, the grain boundary strength of alumina and the matrix whisker interfacial bonding should be improved. To increase the resistance to fatigue, the fracture strength of the alumina grains should be improved by using finer α-alumina particles and the fatigue strength of the whisker have to be increased by improving the uniformity in distribution of β-SiC whiskers during hot pressing.     

Construction of a pseudolarynx after laryngectomy and radical neck dissection. A preliminary report

Oxytocin analogues which combine high oxytocic activities with negligible antidiuretic and pressor activities have been studied. [4-Threonine,7-glycine]oxytocin, [1-(L-2-hydroxy-3-mercaptopropionic acid),4-threonine,7-glycine]oxytocin, and [1-(L-2-hydroxy-3-mercaptopropionic acid)]oxytocin were found to possess the following specific biological activities respectively: rat uterotonic, 270 +/- 10, 337 +/- 23, 1542 +/- 0.4; rat antidiuretic, 0.002 +/- 0.0008, 0.048 +/- 0.005, 40.3 +/- 2.4. The results are analyzed from a conformation-activity viewpoint in a continued attempt to evaluate the scope and limitations of this approach in comparison to structure-activity studies.     

Measurement and Evaluation of Alternative Computer Architectures

The Army/Navy Computer Family Architecture Committee has developed an approach for quantifying the relative performance of alternative computer architectures.     

"High-load" polyethylene glycol-polystyrene (PEG-PS) graft supports for solid-phase synthesis

In the rat dorsal hippocampus and dorsal raphe nucleus, the microiontophoretic application of ergotamine and 5-HT suppressed the firing activity of CA3 pyramidal neurons and 5-HT neurons, an effect antagonized by selective 5-HT1A receptor antagonists. Co-application of ergotamine prevented the inhibitory action of 5-HT on the firing activity of CA3 pyramidal neurons but not of 5-HT neurons, indicating that ergotamine acted as a partial 5-HT1A receptor agonist in the dorsal hippocampus and as a full agonist at 5-HT1A autoreceptors. Ergotamine decreased, in a concentration-dependent manner, the electrically evoked release of [3H]5-HT in preloaded rat and guinea pig hypothalamus slices; this effect was prevented by the nonselective 5-HT receptor antagonist methiothepin but not by the selective 5-HT1B/1D receptor antagonist GR 127935 or the alpha 2-adrenoceptor antagonist idazoxan. Although body temperature in humans remained unchanged following inhaled ergotamine, in the rat, subcutaneously injected ergotamine produced a hypothermia that was prevented by a pretreatment with the 5-HT1A/1B receptor/beta-adrenoceptor antagonist pindolol. Finally in humans, ergotamine did not alter prolactin or adrenocorticotropic hormone levels, but increased growth hormone level, which was prevented by pindolol. Cortisol level was increased in humans by ergotamine, but this enhancement was unaltered by pindolol. In conclusion, the present results suggest that ergotamine acted in the rat brain as a 5-HT1A receptor agonist and as an agonist of terminal 5-HT autoreceptor of a yet undefined subtype. In humans, ergotamine also displayed some 5-HT1A receptor activity but, probably because of lack of receptor selectivity, it did not present the same profile as other 5-HT1A receptor agonists.     

Thyroid hormone export regulates cellular hormone content and response

Actions of thyroid hormones (THs) are determined by intracellular free hormone concentration. Here we report that enhanced TH extrusion via a saturable, cold-sensitive mechanism lowers intracellular TH and causes TH resistance in hepatoma cells. Since these cells overexpress multidrug resistance P-glycoproteins and TH extrusion and resistance are blunted by verapamil, P-glycoproteins may mediate this resistance. Verapamil-inhibitable TH efflux was also found in primary hepatocytes, cardiocytes, and fibroblasts. These findings demonstrate that TH extrusion can modulate TH availability and action in mammalian cells.     

Gonadal hormones influence the immune response to PLP 139-151 and the clinical course of relapsing experimental autoimmune encephalomyelitis

Rotational atherectomy is effective acutely in treating complex coronary disease, but less is known about its long-term clinical outcome. We examined the acute results and late clinical outcome in 178 patients undergoing treatment with this device. Rotational atherectomy was used to treat 240 lesions in 178 individual patients. Nineteen percent had multilesion or staged multivessel procedures, and 71% had AHA-ACC Type B2/C lesions. The procedure was completed successfully in 94% of patients. Major complications occurred in 6% (death 1%, Q-MI 2.8%, and emergency bypass surgery 2.2%). Clinical follow-up was available for 167 (94%) patients at 13+/-6 months. Thirty-five percent required additional catheterization because of recurrent symptoms or an abnormal stress test. Clinical restenosis was confirmed in 18%, and an additional 2.2% of patients had progression of disease in previously untreated segments. At the end of 1 year, 14% had undergone repeat target vessel revascularization. Cumulatively at follow-up, approximately 80% had avoided an acute major complication and repeat revascularization for restenosis. Rotational atherectomy provides excellent acute and good late clinical results. At 1 year follow-up, the likelihood of developing clinical restenosis or significant progression of disease was 1 in 5, and patients had a 1 in 7 chance of requiring revascularization because of restenosis. These findings are encouraging and indicate that rotational atherectomy can be performed safely and with a high degree of acute and late clinical success in complex coronary disease characterized by multivessel or multilesion involvement and a predominance of B2 and C lesions.     

Neutropenia does not prevent etodolac- or indomethacin-induced gastrointestinal damage in the rat

Neutrophils have been implicated in the acute formation of gastric mucosal erosions induced by nonsteroidal antiinflammatory drugs. The aims of the present study were to determine, in rats, the role of neutrophils in the pathogenesis of etodolac- and indomethacin-induced gastrointestinal ulceration and blood loss. Both drugs caused gastrointestinal ulceration, which was associated with increased blood loss, a rise in plasma haptoglobin concentration, and a rise in the number of circulating neutrophils. A marked infiltration of neutrophils occurred only in ileal tissue. Pretreatment with a selective antineutrophil serum induced a significant neutropenia, which failed to inhibit either etodolac- or indomethacin-induced gastrointestinal ulceration and blood loss. A further study demonstrated that the antineutrophil serum did not prevent gastric erosions induced by indomethacin, but it inhibited carrageenan paw edema, which is dependent, in part, on neutrophil infiltration and activation. It is concluded that neutrophils do not contribute to gastrointestinal ulceration and blood loss induced by nonsteroidal antiinflammatory drugs. Furthermore, in contrast with previous studies, our results provide no evidence that neutrophils contribute to indomethacin-induced acute gastric erosion formation.