Memnobotrins and memnoconols: novel metabolites from Memnoniella echinata

Four novel metabolites have been isolated from a rice culture of Memnoniella echinata (JS6308) by solvent extraction and radial silica chromatography. The structures were elucidated by spectroscopic techniques, and the absolute stereochemistry of memnobotrin A determined by X-ray crystallography.     

Bacteriologic and endotoxin analysis of salvaged blood used in autologous transfusions during cardiac operations.

Autologous blood transfusion is a common method of reducing the need for heterologous blood transfusion during cardiac operations. Recently we investigated an outbreak of severe, nonsurgical postoperative bleeding among patients undergoing heart operations and receiving intraoperative transfusion of blood from a cell conservation device (Cell Saver System, Haemonetics Corp., Braintree, Mass.). As a result of this investigation, we conducted a prospective study to determine if bacterial or endotoxin contamination of the blood collected in the Cell Saver System and used for reinfusion during heart operations contributes to postoperative bleeding complications. Patients' blood samples were collected immediately before operation, at the end of cardiopulmonary bypass, 1 hour postoperatively, and from the Cell Saver System. All blood samples were cultured for bacteria, and all plasma samples were assayed for endotoxin. Preoperatively all patients having heart operations were without signs of infection, 33 of 37 blood cultures taken were negative, and none of the plasma samples had detectable endotoxin. After discontinuance of cardiopulmonary bypass but before delivery of blood from the Cell Saver System, bacteria and endotoxin were detected in 11 of 36 (30.6%) and five of 35 (14.3%) of the patients' blood samples, respectively. The blood aspirated from the open chest and collected by the Cell Saver System was culture positive in 30 of 31 (96.8%) samples, and seven of 29 (24.1%) contained endotoxin. One of 28 blood samples collected 1 hour postoperatively was culture positive, and five of 25 samples contained endotoxin. Of 61 total microorganisms isolated, 50 (82%) were coagulase-negative staphylococci, four (6.6%) aerobic diphtheroids, five (8.2%) anaerobic "diphtheroids" (Propionibacterium acnes), and two (3.2%) gram-negative bacilli. Plasma endotoxin concentrations ranged from 10 to 765 pg/ml. No signs of endotoxemia or unusual bleeding were observed intraoperatively or postoperatively in any of the 38 patients. Although blood collected in the Cell Saver System and used for reinfusion during heart operations often was contaminated with gram-positive bacterial commensals of the skin and low concentrations of endotoxin, no adverse effects were noted in the patients.     

Effect of instructions on isokinetic trunk strength testing variability, reliability, absolute value, and predictive validity.

Although isokinetic strength testing has been in use for more than two decades, and numerous studies have addressed isokinetic performance of the lumbar spine, the effect of instructions on isokinetic trunk strength has not been studied. In a sample of 30 healthy women, this study examined the effect of "high-demand" instructions on lumbar strength performance. High-demand instructions were found to have a substantial positive effect on performance variability, reliability, absolute magnitude, and validity. Under these conditions, isokinetic trunk strength was found to be predictive of performance in a frequent lifting-lowering task.     

Ethnographic and secrecy patterns among drug abusers

The underground nature of drug abuse is a major cross-national barrier to the collection of sound epidemiological data. The authors examine some common patterns of secrecy developed by drug abusers to avoid social disapproval or punishment in different socio-cultural settings. Assurances of anonymity and confidentiality may not be sufficient to make the majority of heavy drug abusers "visible" to the researcher. One way to overcome this barrier is to train field staff to recognize certain ethnographic signs i.e. the specific appearance and behaviour of drug abusers that can facilitate identification of target populations.     

The magnetic resonance imaging appearances of the brain in acute carbon monoxide poisoning

AIMS: To describe the magnetic resonance imaging (MRI) appearances of the brain in acute carbon monoxide poisoning, the commonest cause of accidental poisoning in Europe and the U.S.A. To attempt to correlate the imaging findings with patient outcome as an aid to prognosis. MATERIALS AND METHODS: Brain MRI was performed on 19 consecutive patients, who had sustained acute carbon monoxide poisoning, as soon as possible after their referral to the regional Hyperbaric Unit at the Royal Hospital, Haslar. All patients were unconscious on arrival, and had received at least one treatment with hyperbaric oxygen by the time of first MR. The imaging findings were analysed independently by two experienced MR radiologists, with a third radiologist arbitrating on discrepant results. RESULTS: Thirteen male and six female patients, age range 21-70 years (mean 38.7 years) underwent MR an average of 35.6 h (range 6-126 h) following presentation at the referring centre. MR (at 0.5T) revealed abnormalities in the following areas: globus pallidus (n = 12); other basal ganglia [ n = 5: entire lentiform (globus pallidus and putamen), putamen alone, caudate nucleus, thalamus]; white matter (n = 6: periventricular, subcortical, other); cerebral cortex (n = 5), either localized or general; medial temporal lobe in the region of the hippocampus (n = 4). The majority of the patients with hyperintensity in the region of the hippocampus (n = 3) had no other area of cortical involvement. Two patients showed abnormalities in the cerebellum. Normal appearances were seen on the initial MR in seven patients. CONCLUSION: The appearances of the brain following acute CO poisoning are varied, and have previously been the subject of case reports or small studies, most of which have have addressed the delayed sequelae of this condition. This study, the first large series undertaken in the acute phase, confirms that, although the globus pallidus is the commonest site of abnormality in the brain, the effects of CO poisoning are widespread. The extent of damage correlates with clinical outcome, and therefore aids management and prognosis.     

柱前手性衍生化反相高效液相色谱法拆分地佐西平对映异构体的研究

用乙酰葡萄糖异硫氰酸酯(GITC)作柱前手性衍生化试剂,以反相高效液相色谱法成功地拆分了地佐西平对映异构体。在此基础上建立了地佐西平对映异构体纯度和血药浓度测定方法。已用于测定右旋地佐西平的光学纯度和小鼠血药浓度。     

Effects of nicotine on finger tapping rate in non-smokers

Five experiments were conducted investigating the effects of nicotine on finger tapping rate in non-smokers. In each experiment subjects tapped as fast as possible a fixed number of times with one finger on a conventional computer keyboard. In the first experiment tapping rate was increased by two 2 mg doses of a nasal nicotine solution (NNS) but not by an inactive solution. The second study was carried out double-blind and showed that a single 2 mg dose of NNS improved tapping performance by about 5% whereas a very low dose (0.15 mg) NNS and a placebo had no effect. The effect of the NNS was to bring about a sustained increase in tapping rate from the start of each trial. The third study found that the effect of nicotine on tapping was reduced by a single 2.5 mg dose of the central cholinergic blocking agent, mecamylamine, but not by a placebo. Experiment four followed tapping rate for one hour after a dose of two 2 mg NNS and showed that within a subject this behavioural measure can provide a very consistent and sensitive bio-assay of the time course of nicotine effects. The final experiment found that repeated dosing with one 2 mg NNS on an hourly schedule for six hours produced a reliable increase in tapping speed after each dose with no evidence of acute tolerance. The results indicate that nicotine can substantially improve performance by non-smokers on a simple motor task, probably via its action on cholinergic pathways. NNS provides for the first time an effective means of examining the effects of nicotine on non-smokers.     

Evaluation of 5-(Trifluoromethyl)-1,2,4-oxadiazole-Based Class IIa HDAC Inhibitors for Huntington’s Disease

Using an iterative structure–activity relationship driven approach, we identified a CNS-penetrant 5-(trifluoromethyl)-1,2,4-oxadiazole (TFMO, 12) with a pharmacokinetic profile suitable for probing class IIa histone deacetylase (HDAC) inhibition in vivo. Given the lack of understanding of endogenous class IIa HDAC substrates, we developed a surrogate readout to measure compound effects in vivo, by exploiting the >100-fold selectivity compound 12 exhibits over class I/IIb HDACs. We achieved adequate brain exposure with compound 12 in mice to estimate a class I/IIb deacetylation EC₅₀, using class I substrate H4K12 acetylation and global acetylation levels as a pharmacodynamic readout. We observed excellent correlation between the compound 12 in vivo pharmacodynamic response and in vitro class I/IIb cellular activity. Applying the same relationship to class IIa HDAC inhibition, we estimated the compound 12 dose required to inhibit class IIa HDAC activity, for use in preclinical models of Huntington’s disease.