Diagnosis and Treatment of Amanita Phalloides-Type Mushroom Poisoning: Use of Thioctic Acid

The number of cases of mushroom poisoning is increasing as a result of the increasing popularity of “wild” mushroom consumption. Amanitin and phalloidin cytotoxins found in some Amanita and Galerina species produce the most severe and frequent life-threatening symptoms of Amanita phalloidestype poisoning. Delay in onset of symptoms, individual susceptibility variation and lack of rapid and reliable identification have contributed to the significant morbidity and mortality of this type of poisoning.A rapid chromatographic assay for identifying the potent cytotoxins and apparently successful management using thioctic acid of two cases of A. phalloides-type mushroom poisoning are reported. All known cases of A. phalloides-type mushroom poisoning treated with thioctic acid in the United States are summarized.     

The ancestor of the <Emphasis Type="Italic">Paulinella</Emphasis> chromatophore obtained a carboxysomal operon by horizontal gene transfer from a <Emphasis Type="Italic">Nitrococcus</Emphasis>-like γ-proteobacterium

Background  

Paulinella chromatophora is a freshwater filose amoeba with photosynthetic endosymbionts (chromatophores) of cyanobacterial origin that are closely related to free-living Prochlorococcus and Synechococcus species (PS-clade). Members of the PS-clade of cyanobacteria contain a proteobacterial form 1A RubisCO (ribulose-1,5-bisphosphate carboxylase/oxygenase) that was acquired by horizontal gene transfer (HGT) of a carboxysomal operon. In rDNA-phylogenies, the Paulinella chromatophore diverged basal to the PS-clade, raising the question whether the HGT occurred before or after the split of the chromatophore ancestor.     

Intrauterine growth restriction decreases pulmonary alveolar and vessel growth and causes pulmonary artery endothelial cell dysfunction in vitro in fetal sheep

Intrauterine growth restriction (IUGR) increases the risk for bronchopulmonary dysplasia (BPD). Abnormal lung structure has been noted in animal models of IUGR, but whether IUGR adversely impacts fetal pulmonary vascular development and pulmonary artery endothelial cell (PAEC) function is unknown. We hypothesized that IUGR would decrease fetal pulmonary alveolarization, vascular growth, and in vitro PAEC function. Studies were performed in an established model of severe placental insufficiency and IUGR induced by exposing pregnant sheep to elevated temperatures. Alveolarization, quantified by radial alveolar counts, was decreased 20% (P < 0.005) in IUGR fetuses. Pulmonary vessel density was decreased 44% (P < 0.01) in IUGR fetuses. In vitro, insulin increased control PAEC migration, tube formation, and nitric oxide (NO) production. This response was absent in IUGR PAECs. VEGFA stimulated tube formation, and NO production also was absent. In control PAECs, insulin increased cell growth by 68% (P < 0.0001). Cell growth was reduced in IUGR PAECs by 29% at baseline (P < 0.01), and the response to insulin was attenuated (P < 0.005). Despite increased basal and insulin-stimulated Akt phosphorylation in IUGR PAECs, endothelial NO synthase (eNOS) protein expression as well as basal and insulin-stimulated eNOS phosphorylation were decreased in IUGR PAECs. Both VEGFA and VEGFR2 also were decreased in IUGR PAECs. We conclude that fetuses with IUGR are characterized by decreased alveolar and vascular growth and PAEC dysfunction in vitro. This may contribute to the increased risk for adverse respiratory outcomes and BPD in infants with IUGR.     

Identification of a new mutation in medium-chain acyl-CoA dehydrogenase (MCAD) deficiency.

A mutation involving an A-to-G nucleotide replacement at position 985 of the medium-chain acyl-CoA dehydrogenase (MCAD) cDNA was found in homozygous form in 18 unrelated MCAD-deficient families and in heterozygous form in 4 families. By PCR amplification and sequencing of cDNA from a compound heterozygote, we have detected a new mutation in an MCAD-deficient patient in whom one MCAD allele produces mRNA that is missing 4 bp in the MCAD cDNA, while the other allele carries the A-to-G-985 mutation. The presence of this 4-bp deletion was confirmed in the patient's genomic DNA by dot-blot hybridization with allele-specific oligonucleotide probes and by restriction analysis of PCR products. A rapid screening test for this 4-bp deletion was developed, based on mismatched primer PCR amplification. The deletion created a new restrictive-enzyme site which yielded two DNA fragments. The 4-bp deletion was not found in the three remaining MCAD chromosomes not harboring the A-to-G-985 mutation, nor it was present in 20 chromosomes from 10 unrelated normal Caucasians. The PCR-based method for screening these two mutations can detect over 93% of all MCAD mutations.     

The effect of chlortetracycline treatment and its subsequent withdrawal on multi-resistant Salmonella enterica serovar Typhimurium DT104 and commensal Escherichia coli in the pig

AIMS: To investigate the effect of a therapeutic and sub-therapeutic chlortetracycline treatment on tetracycline-resistant Salmonella enterica serovar Typhimurium DT104 and on the commensal Escherichia coli in pig. METHODS AND RESULTS: Salmonella Typhimurium DT104 was orally administered in all pigs prior to antibiotic treatment, and monitored with the native E. coli. Higher numbers of S. Typhimurium DT104 were shed from treated pigs than untreated pigs. This lasted up to 6 weeks post-treatment in the high-dose group. In this group, there was a 30% increase in E. coli with a chlortetracycline minimal inhibitory concentration (MIC) > 16 mg l-1 and a 10% increase in E. coli with an MIC > 50 mg l-1 during and 2 weeks post-treatment. This effect was less-pronounced in the low-dose group. PCR identified the predominant tetracycline resistance genes in the E. coli as tetA, tetB and tetC. The concentration of chlortetracycline in the pig faeces was measured by HPLC and levels reached 80 microg g-1 faeces during treatment. CONCLUSION: Chlortetracycline treatment increases the proportion of resistant enteric bacteria beyond the current withdrawal time. SIGNIFICANCE AND IMPACT OF THE STUDY: Treated pigs are more likely to enter abattoirs with higher levels of resistant bacteria than untreated pigs promoting the risk of these moving up the food chain and infecting man.     

The protective role of dietary unsaturated fatty acids against 2-undecanone-induced pupal mortality and deformity in Helicoverpa zea

As previously reported, the addition of 2-undecanone to the diet of Helicoverpa (Heliothis) zea (Boddie) causes pupal mortality and deformity. These toxic effects are antagonised by the addition of the unsaturated fatty acid linolenic acid to diet, with pupal deformity eliminated and mortality reduced by as much as one-half. Similar results were obtained with two other unsaturated fatty acids, linoleic and oleic acids, but not with saturated stearic acid. These unsaturated fatty acids also increased pupal weight and developmental time. However, measurement of food consumption indicated that the effect of unsaturated fatty acids on pupal mortality is not an artifact of dilution of the fatty acid dietary dosage by an increased body size or of evaporation of 2-undecanone during prolonged larval development.     

Temporal mating isolation driven by a behavioral gene in Drosophila

Speciation is the evolutionary process in which new barriers to gene exchange are created. These barriers may be physical, leading to spatial separation of subpopulations and resulting in allopatric speciation, or they may be temporal, giving rise to allochronic speciation, and may include the time of day or the time of year when mating takes place. Drosophila melanogaster and D. pseudoobscura show different temporal patterns of circadian locomotor activity that are determined by the circadian clock gene period (per). Genes that control aspects of behavior that might be relevant to courtship and mating, such as locomotor patterns, become obvious candidates for involvement in the speciation process. However, evidence for the role of individual genes in the mechanism of mate choice has proved elusive. We have used transgenic flies carrying the natural per genes from these two Drosophila species to reveal that per has the potential to provide the permissive conditions for speciation, by affecting mate choice through a mechanism involving the species-specific timing of mating behavior.     

Non-peptide oxytocin agonists

A library of compounds targeted to the vasopressin/oxytocin family of receptors was screened for activity at a cloned human oxytocin receptor using a reporter gene assay. Potency and selectivity were optimised to afford compound 39, EC50 = 33 nM. This series of compounds represents the first disclosed, non-peptide, low molecular weight agonists of the hormone oxytocin (OT).