Serious lead poisoning in childhood: Still a problem after a century

Objective: To describe a series of patients with clinically significant lead poisoning. Methodology: A case series of nine patients with lead poisoning who required inpatient management, identified through a Clinical Toxicology Service. Results: Nine children presented with clinically significant lead poisoning. The median serum lead was 2.5 mumol/L (range 1.38-4.83). Eight of the children were exposed to lead-based paint, with seven due to dust from sanded lead paint during house renovations. Serial blood determinations suggested re-exposure in four of the patients, and in one of these patients the re-exposure was from a different source of lead. Eight of the patients required chelation therapy. Conclusions: Serious lead poisoning continues to occur and there appears to be complacency regarding the hazard posed by lead paint in old houses.

Ability of some plant extracts, traditionally used to treat ciguatera fish poisoning, to prevent the in vitro neurotoxicity produced by sodium channel activators

The effects of 31 plant extracts, which most are traditionally used to treat ciguatera fish poisoning in the Pacific area, were Studied on the cytotoxicity of mouse neuroblastoma cells produced by ouabain, veratridine and/or brevetoxin-3 or Pacific ciguatoxin-1. The cell viability was determined using a quantitative colorimetric method. A marked cytotoxicity of seven of the 31 plant extracts studied, was observed. Despite this, these plant extracts were suspected to contain active compound(s) against the cytotoxicity produced by brevetoxin (2 extracts), brevetoxin, ouabain and/or veratridine (3 extracts), or only against that of ouabain and/or veratridine (2 extracts). Among the 24 plant extracts that exhibited by themselves no cytotoxicity, 22 were active against the effect of brevetoxin or against that of both veratridine and brevetoxin. similar results were obtained when the seven most active plant extracts were reassayed using ciguatoxin instead of brevetoxin. In conclusion, the present work reports the first activity assessment of some plant extracts, achieved in vitro on a quite large scale. The fact that 27 plant extracts were found to exert, in vitro, a protective effect against the action of ciguatoxin and/or brevetoxin, paves the way for finding new active compounds to treat ciguatera fish poisoning, provided these compounds also reverse the effects of sodium channel activators. (c) 2005 Elsevier Ltd. All rights reserved.

The population pharmacokinetics of citalopram after deliberate self-poisoning: A Bayesian approach

Defining the pharmacokinetics of drugs in overdose is complicated. Deliberate self-poisoning is generally impulsive and associated with poor accuracy in dose history. In addition, early blood samples are rarely collected to characterize the whole plasma-concentration time profile and the effect of decontamination on the pharmacokinetics is uncertain. The aim of this study was to explore a fully Bayesian methodology for population pharmacokinetic analysis of data that arose from deliberate self-poisoning with citalopram. Prior information on the pharmacokinetic parameters was elicited from 14 published studies on citalopram when taken in therapeutic doses. The data set included concentration-time data from 53 patients studied after 63 citalopram overdose events (dose range: 20-1700 mg). Activated charcoal was administered between 0.5 and 4 h after 17 overdose events. The clinical investigator graded the veracity of the patients' dosing history on a 5-point ordinal scale. Inclusion of informative priors stabilised the pharmacokinetic model and the population mean values could be estimated well. There were no indications of non-linear clearance after excessive doses. The final model included an estimated uncertainty of the dose amount which in a simulation study was shown to not affect the model's ability to characterise the effects of activated charcoal. The effect of activated charcoal on clearance and bioavailability was pronounced and resulted in a 72% increase and 22% decrease, respectively. These findings suggest charcoal administration is potentially beneficial after citalopram overdose. The methodology explored seems promising for exploring the dose-exposure relationship in the toxicological settings.

Pyrrolizidine alkaloids in Senecio madagascariensis from Australia and Hawaii and assessment of possible livestock poisoning

The alkaloid content of Senecio madagascariensis collected from Australia and Hawaii was examined. Alkaloids were identified from the above ground whole plant (stems, leaves and flowers) by GUMS analysis and included: senecivernine, senecionine, integerrimine, senkirkine, mucronatinine, retrosine, usaramine, otosenine, acetylsenkirkine, desacetyldoronine, florosenine and doronine. Plant material collected from the Hawaiian Islands was found to be identical in pyrrolizidine alkaloid content to that from a single composite collection made from northern New South Wales, Australia. Overall, no appreciable differences in alkaloid content were found between locations, whereas variation among individual plants was evident. The average total pyrrolizidine alkaloid content varied from a low of 217 mu g/g to a high of 1990 mu g/g (dry weight basis) among the locations. Based on comparable alkaloid content and documented pyrrolizidine alkaloidosis cases from Australia, S. madagascariensis may pose a significant risk to livestock grazing heavily infested ranges on the Hawaiian Islands. (c) 2006 Elsevier Ltd. All rights reserved.

Synaptogenesis in the mushroom body calyx during metamorphosis in the honeybee Apis mellifera: An electron microscopic study

The goals of this study are to determine relationships between synaptogenesis and morphogenesis within the mushroom body calyx of the honeybee Apis mellifera and to find out how the microglomerular structure characteristic for the mature calyx is established during metamorphosis. We show that synaptogenesis in the mushroom body calycal neuropile starts in early metamorphosis (stages P1-P3), before the microglomerular structure of the neuropile is established. The initial step of synaptogenesis is characterized by the rare occurrence of distinct synaptic contacts. A massive synaptogenesis starts at stage P5, which coincides with the formation of microglomeruli, structural units of the calyx that are composed of centrally located presynaptic boutons surrounded by spiny postsynaptic endings. Microglomeruli are assembled either via accumulation of fine postsynaptic processes around preexisting presynaptic boutons or via ingrowth of thin neurites of presynaptic neurons into premicroglomeruli, tightly packed groups of spiny endings. During late pupal stages (P8-P9), addition of new synapses and microglomeruli is likely to continue. Most of the synaptic appositions formed there are made by boutons (putative extrinsic mushroom body neurons) into small postsynaptic profiles that do not exhibit presynaptic specializations (putative intrinsic mushroom body neurons). Synapses between presynaptic boutons characteristic of the adult calyx first appear at stage P8 but remain rare toward the end of metamorphosis. Our observations are consistent with the hypothesis that most of the synapses established during metamorphosis provide the structural basis for afferent information flow to calyces, whereas maturation of local synaptic circuitry is likely to occur after adult emergence.