The addition of IV very low dose ketamine infusion regimen did not improve postoperative analgesia. Side effects were not increased with low dose ketamine.

ORIGINAL RESEARCHwith a model developed using traditional stepwise logistic regression (AUC = 0.69, 95% CI 0.57-0.82). Calibration for all models and feature sets was poor. CONCLUSIONS: We developed machine learning prediction models for post-operative delirium that performed better than chance and are comparable with traditional stepwise logistic regression. Delirium proved to be a phenotype that was difficult to predict with appreciable accuracy.

Daidzin is a potent, selective, and reversible inhibitor of human mitochondrial aldehyde dehydrogenase (ALDH) that suppresses free-choice ethanol intake by Syrian golden hamsters. Other ALDH inhibitors, such as disulfiram (Antabuse) and calcium citrate carbimide (Temposil), have also been shown to suppress ethanol intake of laboratory animals and are thought to act by inhibiting the metabolism ofacetaldehyde produced from ingested ethanol. To determine whether or not daidzin inhibits acetaldehyde metabolism in vivo, plasma acetaldehyde in daidzin-treated hamsters was measured after the administration of a test dose of ethanol.Daidzin treatment (150 mg/kg per day i.p. for 6 days) significantly suppresses (>70%) hamster ethanol intake but does not affect overall acetaldehyde metabolism. In contrast, after administration of the same ethanol dose, plasma acetaldehyde concentration in disulfiram-treated hamsters reaches 0.9 mM, 70 times higher than that of the control. In vitro, daidzin suppresses hamster liver mitochondria-catalyzed acetaldehyde oxidation very potently with an IC50 value of 0.4 ,IM, which is substantially lower than the daidzin concentration (70 ,uM) found in the liver mitochondria of daidzin-treated hamsters. These results indicate that (i) the action of daidzin differs from that proposed for the classic, broad-acting ALDH inhibitors (e.g., disulfiram), and (ii) the daidzin-sensitive mitochondrial ALDH is not the one and only enzyme that is essential for acetaldehyde metabolism in golden hamsters.Daidzin, a glucosylated isoflavone isolated from Radix puerariae, suppresses free-choice ethanol intake by Syrian golden hamsters (1). It also potently and selectively inhibits human mitochondrial aldehyde dehydrogenase (ALDH) (2). Almost half of all Asians have inherited an inactive variant form of mitochondrial ALDH, and in this population group alcohol abuse/alcoholism is rare (3-5). Hence, daidzin might be assumed to act by mimicking the consequences of this mutation of the mitochondrial ALDH gene. Individuals carrying the null mitochondrial ALDH gene are not known to suffer from any physiologic problems, except for a significantly compromised capacity to metabolize acetaldehyde. When they consume even small amounts of ethanol (6) their blood acetaldehyde concentration increases markedly.The premise that acetaldehyde accumulation after ethanol consumption may deter further drinking has attracted considerable attention ever since disulfiram was introduced as a therapeutic agent for human alcohol addiction. It was first proposed as an aversive drug based on the observation that workers in the rubber industry who had been exposed to thiuram compounds experienced unpleasant effects after drinking (7). Since then, it has been established that disulfiram-as well as other ALDH inhibitors-suppresses the metabolism of acetaldehyde and causes it to accumulate in peripheral tissues when ethanol is consumed. As a consequence, it induces a broad spectrum of disagreeable effects (8). Association of these no...

The dose effect of pure daidzin on the suppression of ethanol intake in Syrian golden hamsters was compared with that of crude daidzin contained in a methanol extract of Radix puerariae (RP MATERIALS AND METHODSRP extract was prepared by refluxing 100 g of fibrous RP (Tung Ren Tang Traditional Chinese Medicine Extraction Factory, Beijing) in 700 ml of methanol for 5 h. The methanol extract was filtered through Whatman no. 1 filter paper. The residue was refluxed in 700 ml of fresh methanol for another 5 h and also filtered. The combined filtrates were evaporated under vacuum to yield a syrup that was suspended in 200 ml of water and dried to a powder by lyophilization. The extract was analyzed for daidzin, daidzein, daidzein-4',7-diglucoside, puerarin, genistin, genistein, and formononetin by HPLC. The column (Beckman C18, 5 ,um, 4.6 mm x 25 cm, IP) was eluted at 1 ml/min with a linear acetonitrile gradient (0-40 min, 12-36%) in 0.1% trifluoroacetic acid. Pure daidzin and daidzein were synthesized according to published procedures and identified by mass and NMR spectroscopy (5, 6). Daidzein-4',7-diglucoside was synthesized by reacting 1 mol of daidzein, 2.1 mol of 2,3,4,6-tetra-0-acetyl-a-D-glucopyranosyl bromide, and 2.1 mol of sodium ethoxide at room temperature for 4 h.Reaction products were precipitated with ethanol and acetyl groups were removed with 1 M NaOH. Reaction side products were precipitated by acidification and daidzein-4',7-diglucoside in the supernatant was further purified on a semipreparatory HPLC column and identified by NMR and mass spectroscopy. Genistein, genistin, formononetin, and puerarin were products of Indofine Chemical (Somerville, NJ). Daidzin-supplemented RP extract was prepared by sonicating 5 g of RP extract and 200 mg of synthetic daidzin in 700 ml of methanol for 10 min. Methanol was then removed by flash evaporation on a 50°C water bath. RP extract and daidzin-supplemented RP extract contain 22 and 62 mg of daidzin per g dry extract, respectively.Animal Drinking Experiments. The effect of various agents on ethanol intake was assessed with golden hamsters housed in metabolic cages under a two-bottle free-choice paradigm as described (3,4