Polarization rotation via a monoclinic phase in the piezoelectric 92% PbZn(1/3)Nb(2/3)O3-8% PbTiO3.

The origin of ultrahigh piezoelectricity in the relaxor ferroelectric PbZn(1/3)Nb(2/3)O3-PbTiO3 was studied with an electric field applied along the [001] direction. The zero-field rhombohedral R phase starts to follow the direct polarization path to tetragonal symmetry via an intermediate monoclinic M phase, but then jumps irreversibly to an alternate path involving a different type of monoclinic distortion. Details of the structure and domain configuration of this novel phase are described. This result suggests that there is a nearby R-M phase boundary as found in the Pb(Ti,Zr)O3 system.

Hibernation-induction trigger. II. In vitro effects of prairie dog plasma albumin on mouse vas deferens contractility.

Involvement of opioid molecules in hibernation is well established, with the delta opioid receptor implicated in hibernation induction. Previous studies have shown that plasma albumin fractions (PAFs) from hibernating mammals contain an uncharacterized ligand called "hibernation-induction trigger" (HIT), which causes inhibition of induced contractility in the guinea pig ileum (GPI). In part I of this study, we described effects of PAF from two species of prairie dogs on induced contractility of the GPI. In the present study (part II), we examine the response of the mouse vas deferens (MVD), which is populated with the delta receptor subtype, to increasing concentrations of PAF from the white-tailed prairie dog (WT) and the black-tailed prairie dog (BT). Dose-response curves of lyophilized PAF yielded IC50 values (mg) (mean dose that inhibits contractility to 50% of control) of 11.0 for summer WT, 10.6 for hibernating WT, 9.4 for summer BT, 12.2 for winter active BT, and 4.7 for winter hibernating BT. These results suggest that delta opioid (HIT) is present in both species throughout the calendar year and that the induction of hibernation may involve not only levels of opioid but also dynamic interactions between endogenous opioid and its receptors.

Alcohol estimation at necropsy: epidemiology, economics, and the elderly.

AIMS: To gather data on blood alcohol concentrations in a forensic necropsy population and to analyse the information on trends that may predict where alcohol testing is going to prove cost-effective. METHODS: Alcohol assays were performed on blood, urine, and vitreous samples in 1620 consecutive medicolegal necropsy examinations. RESULTS: Alcohol was detected in only 7% of natural deaths from all causes and in four of 40 deaths categorised as unknown/obscure. Alcohol concentrations > or = 350 mg/100 ml were found in nine drug/alcohol abuse deaths (range 362-506 mg/100 ml), five accidental deaths (356-504 mg/100 ml), and one homicide victim (400 mg/100 ml). Those categorised as alcohol abusers were represented in all but one category of death (unknown/obscure deaths in males), showing that many true alcoholics die with their alcoholism rather than of it; 39% of males and 34% of females with histories of alcohol abuse had alcohol present in their blood at necropsy at concentrations > or = 50 mg/100 ml, v only 9% (male) and 6% (female) without such history. CONCLUSIONS: The study highlights the problems of elderly and "hidden" alcoholics and illustrates cases where routine assays would provide additional significant information. Routine alcohol testing is useful in all cases of suspected unnatural death but universal testing of forensic necropsies is not cost-effective.

Intussusception: agonal phenomenon or cause of death?

This paper describes two cases of small intestinal intussusception, one in a child and one in an adult, where the findings at autopsy were atypical. The significance of intussusception in this situation is discussed and the literature related to deaths accompanied by acute small intestinal intussusception in the adult and paediatric population is reviewed. It is concluded that the findings represent a true pathological entity and not an 'agonal' event.

Postmortem diffusion of drugs from gastric residue: an experimental study.

Postmortem drug diffusion from gastric residue was assessed in a human cadaver model. Fifty milligrams of amitriptyline (Ami) and 5 g of paracetamol (Par) suspended in 350 ml of 10% methanol, 0.1 N HCl, and 50 ml urograffin with 5 g lithium carbonate (alkaline model) or without lithium (acidic model) was instilled into the stomach through an esophageal tube via a neck dissection. Multiple samples were obtained after 48 h at room temperature (range in mean hourly room temperature: 15.6-20.7 degrees C, n = 9). The pH of the gastric contents (alkaline model range = 8.3-8.9, n = 5; acidic model range = 3.4-3.8, n = 5) had no significant effect. Drug diffusion was most marked in the left lung base, with drug concentrations (micrograms/g) of 0.1-13.9 for Ami, 65-524 for Par, and 13-161 for lithium. Similarly affected were the left lobe of the liver (Ami, 0.1-54.9; Par, 7-218; lithium, 7-39), the spleen (Ami, 0.6-24.3; Par, 104-663; lithium, 27-106), and pericardial fluid (Ami, 0-4.5; Par, 48-641; lithium, 12-56). Diffusion into gallbladder bile, cardiac blood, aortic blood, and blood of the inferior vena cava was less severe. The left kidney and left lung were more severely affected than the right kidney and lung, and similarly the left and right psoas muscles. Least affected was the right anterior lobe of the liver and the lung apexes. This phenomenon may significantly influence drug concentrations in liver and in blood samples obtained from the torso, and consequently liver/blood drug ratios. To circumvent the problem of postmortem drug diffusion from the stomach, it is recommended that blood be sampled from a peripheral vessel, skeletal muscle from a limb, liver from deep within the right lobe, and lung from the apex rather than the base.

"ADAM' or "EVE'?--a toxicological conundrum.

The 3,4-methylenedioxy ring-substituted amphetamines, including "ADAM' and "EVE', are currently popular drugs of abuse. Adverse reactions are reported in the clinical literature but few fatal cases are documented and little toxicological data is available to guide those determining the cause or manner of death in such cases. We report two deaths presenting in a similar manner and with similar clinical features. Various body fluid samples were analysed for amphetamines by gas chromatography/mass spectrometry. In one case, amphetamine alone was detected at levels of 1.54 mg/l and 1.47 mg/l in postmortem blood and admission serum, respectively. The other involved several 3,4-methylenedioxy ring-substituted amphetamines, namely MDA, MDMA and MDEA, at levels of 0.25 mg/l, 0.43 mg/l and 0.3 mg/l, respectively in postmortem femoral blood and 0.24 mg/l, 0.55 mg/l and 0.49 mg/l in admission blood. The interpretation of these toxicological results and some novel legal issues are discussed.

Creatine kinase BB and neuron-specific enolase in cerebrospinal fluid in the diagnosis of brain insult.

Cerebrospinal fluid (CSF) markers provide useful information about the extent of brain damage. These biochemical indices may also be used when postmortem histopathological examination does not confirm antemortem brain insult. Seven biochemical parameters--creatine kinase (CK), creatine kinase BB isoenzyme (CK-BB), lactate dehydrogenase (LDH), gamma-glutamyltransferase, aldolase, leucine aminopeptidase (LAP), and neuron-specific enolase (NSE)--were analyzed in CSF from 82 cadavers. Case studies were categorized into one of four diagnostic groups. There were 15 cases of head trauma, 23 of hypoxia (hangings, carbon monoxide, and drug poisonings), 23 sudden cardiac death, and 21 miscellaneous cases. The degree of craniocerebral trauma was graded. In CSF there was a statistically significant correlation between the severity of craniocerebral trauma and levels of CK, CK-BB, aldolase, LDH, and LAP. CSF CK-BB [median U/L (range)] for the groupings of head trauma, hypoxia, sudden cardiac death, and miscellaneous were, respectively, 873 (1-12,100), 26 (2-2,780), 16 (1-42), and 18 (0-2,780). Corresponding CSF CK levels were 9,370 (28-67,842), 101 (18-36,840), 180 (10-29,622), and 264 (17-26,556). There were no statistical significant differences among the NSE concentrations in the four diagnostic groups. The testing of biochemical markers could be a reliable indicator of the degree of brain insult in support of morphological studies.

Evaluating suspected co-proxamol overdose.

In three instances of suicidal poisoning by co-proxamol (paracetamol and dextropropoxyphene) blood samples were obtained from 11 sites together with eight tissue samples, bile, urine, gastric contents and duodenal contents. Site-dependent differences in blood propoxyphene concentration varied between the three cases but concentrations were consistently lowest in peripheral blood and highest in central sites: 3.9-5.5 (pulmonary vein) mg/l; 4.6-25 (pulmonary vein) mg/l; 3.2-40 (aorta) mg/l. There was a less than twofold variation in corresponding blood paracetamol concentrations. Reference data on fatal propoxyphene blood concentrations do not specify the blood sampling site and can be misleading. The intra-individual variability of propoxyphene concentrations in blood in these three cases underscores this problem. Tissue concentrations of propoxyphene showed considerable inter-individual variability in degree and pattern. Tissue concentrations of paracetamol showed a less than twofold intra-individual variation. Body drug loads were calculated by two methods: from organ weights and tissue concentrations; from published volume of distribution data (Vd). For paracetamol the body drug load is underestimated by the organ weight calculation but the Vd calculation approximates the suspected dose based on anamnestic information. For propoxyphene the body drug load is seriously underestimated by the organ weight calculation and overestimated up to 2.5 times by the Vd calculation. Since the two drugs have a fixed ratio in co-proxamol then the dose of propoxyphene (the effective lethal agent) can be inferred from the paracetamol dose calculated by Vd. This approach may be applicable to cases of overdose with other compounded drug preparations.

Orientational disorder in solvent-free solid c70.

The high-temperature structure of solvent-free C(70) has been determined with high-resolution x-ray powder difraction and electron microscopy. Samples crystallized from solution form hexagonal close-packed crystals that retain an appreciable amount of residual toluene, even after prolonged heating. Samples prepared by sublimation, which contain no detectable solvent, are primarily face-centered cubic with some admixture of a hexagonal phase. The relative volume of the hexagonal phase can be further reduced by annealing. The structures of both phases are described by a model of complete orientational disorder. The cubic phase contains an appreciable density of stacking faults along the [111] direction.

Synchrotron X-ray Diffraction Measurements of Single-Crystal Hydrogen to 26.5 Gigapascals.

The crystal structure and equation of state of solid hydrogen have been determined directly to 26.5 gigapascals at room temperature by new synchrotron x-ray diffraction techniques. Solid hydrogen remains in the hexagonal close-packed structure under these pressure-temperature conditions and exhibits increasing structural anisotropy with pressure. The pressure-volume curve determined from the x-ray data represents the most accurate experimental measurement of the equation of state to date in this pressure range. The results remove the discrepancy between earlier indirect determinations and provide a new experimental constraint on the molecular-to-atomic transition predicted at higher pressures.

Mechanism of calmodulin inhibition of cAMP-dependent protein kinase activation of phosphorylation kinase.

The activation of phosphorylase kinase (EC 2.7.1.38; ATP:phosphorylase b phosphotransferase) by the catalytic subunit of cAMP-dependent protein kinase (EC 2.7.1.37; ATP:protein phosphotransferase) is inhibited by calmodulin. The mechanism of that inhibition has been studied by kinetic measurements of the interactions of the three proteins. The binding constant for calmodulin with phosphorylase kinase was found to be 90 nM when measured by fluorescence polarization spectroscopy. Glycerol gradient centrifugation studies indicated that 1 mol of calmodulin was bound to each phosphorylase kinase. Phosphorylation of the phosphorylase kinase did not reduce the amount of calmodulin bound. Kinetic studies of the activity of the catalytic subunit of cAMP-dependent protein kinase on phosphorylase kinase as a function of phosphorylase kinase and calmodulin concentrations were performed. The results of those studies were compared with mathematical models of four different modes of inhibition: competitive, noncompetitive, substrate depletion, and inhibition by a complex between phosphorylase kinase and calmodulin. The data conform best to the model in which the inhibitory species is a complex of phosphorylase kinase and calmodulin. The complex apparently competes with the substrate, phosphorylase kinase, which does not have exogenous calmodulin bound to it. In contrast, the phosphorylation of the synthetic phosphate acceptor peptide, Kemptide, is not inhibited by calmodulin.

Inhibition by calmodulin of the cAMP-dependent protein kinase activation of phosphorylase kinase.

Calmodulin is shown to inhibit both the activation and phosphorylation of phosphorylase kinase by cAMP-dependent protein kinase. Maximal inhibition of both processes was approximately 66% at the highest calmodulin concentration tested (5.5 microM). It was found that the inhibition of phosphorylation was calcium-dependent, reversible by trifluoperazine, and specific for the beta subunit of phosphorylase kinase with no significant inhibition of phosphorylation of the alpha subunit. This inhibitory activity of calmodulin appears to be due to an interaction between calmodulin and the substrate, phosphorylase kinase. This finding implies either that the site of exogenous calmodulin interaction with phosphorylase kinase is at the beta subunit or that this interaction results in a conformational change of phosphorylase kinase that inhibits the interaction between cAMP-dependent protein kinase and the beta subunit of phosphorylase kinase. The beta subunit may contain a regulatory site that is recognized by either protein kinase or calmodulin. These findings further substantiate the role of the beta subunits in the activation of phosphorylase kinase and provide an additional example of substrate-directed control of phosphorylation.

Aspirin-induced oral lesion: report of case.

Aspirin is one of the most extensively used medications and has many beneficial effects. However, its injudicious use can produced local as well as systemic undesirable effects. A case of aspirin burn of the oral mucosa is presented. The lesion was in an unusual location. However, the history and the successful results from discontinuance of the drug supported the provisional diagnosis.