A national epidemic of campylobacteriosis in Iceland, lessons learned.

Epidemics often result in organizational, policy and technical changes within a country. In 1999, an epidemic of campylobacteriosis was reported in Iceland. The recent availability of fresh poultry products in the marketplace was suggested as the source of infection. This paper reports on the context of the epidemic, reviews interventions implemented to prevent campylobacteriosis, and discusses lessons learned. A retrospective study of interventions implemented in Iceland from June 1995 to December 2007 was conducted by interviewing key informants and reviewing Iceland's literature. Cumulative incidence rates of domestic campylobacteriosis by year and average incidence rates per epidemic period were calculated. Interventions included on-farm surveillance of Campylobacter, producer education, enhanced biosecurity measures, changes in poultry processing, a leak-proof packaging policy, a freezing policy for products from Campylobacter-positive poultry flocks, consumer education, and the creation of a legislated inter-organizational response committee. These interventions appear to have collectively contributed to a decrease in campylobacteriosis' incidence rate near pre-epidemic baseline levels. Expert consultations revealed that the implementation of a Campylobacter surveillance program in poultry and the freezing policy were critical to controlling the disease in the Icelandic population. It was also recognized that new multidisciplinary collaborations among public health, veterinary, and food safety authorities and a sustained co-operation from the poultry industry were integral factors to the mitigation of the epidemic. Iceland's response to the campylobacteriosis epidemic is a lesson learned of inter-disciplinary and inter-organizational precautionary public health action in the face of a complex public health issue.

An investigation of cancer incidence in a First Nations community in Alberta, Canada, 1995-2006.

OBJECTIVE: To determine colorectal and overall cancer incidence as part of a three-pronged investigation in response to the concerns of a First Nations community in Alberta, Canada, located close to sulfur-rich natural gas installations, and to determine whether the incidence of cancers observed in this reserve was higher than expected. METHODS: A population dataset with information identifying First Nations status and band affiliation was linked to the Alberta Cancer Registry to determine cancer incidence cases between 1995 and 2006 for on- and off-reserve study populations. Using indirect standardized incidence ratios, observed cancer incidence cases for the study populations were compared with cases expected based on three separate reference populations. RESULTS: Observed colorectal and overall cancer incidence cases within the First Nations community were not higher than expected. Cervical cancer incidence cases, however, were higher than expected for on- and off-reserve populations; public health measures designed to address this risk have been implemented and on-going surveillance of cancer incidence in the community will be maintained.

Neuroprotective efficacy of microvascularly-localized versus brain-penetrating antioxidants.

The 21-aminosteroid (lazaroid) tirilazad mesylate has been demonstrated to be a potent inhibitor of lipid peroxidation and to reduce traumatic and ischemic damage in a number of experimental models. Currently, tirilazad is being actively investigated in phase III clinical trials in head and spinal cord injury, ischemic stroke and subarachnoid hemorrhage. This compound acts in large part to protect the microvascular endothelium and consequently to maintain normal blood-brain barrier (BBB) permeability and cerebral blood flow autoregulatory mechanisms. However, due to its limited penetration into brain parenchyma, tirilazad has generally failed to affect delayed neuronal damage to the selectively vulnerable hippocampal CA1 and striatal regions. Recently, we have discovered a new group of antioxidant compounds, the pyrrolopyrimidines, which possess significantly improved ability to penetrate the BBB and gain direct access to neural tissue. Several compounds in the series, such as U-101033E, have demonstrated greater ability to protect the CA1 region in the gerbil transient forebrain ischemia model with a post-ischemic therapeutic window of at least four hours. In addition, U-101033E has been found to reduce infarct size in the mouse permanent middle cerebral artery occlusion model in contrast to tirilazad which is minimally effective. These results suggest that antioxidant compounds with improved brain parenchymal penetration are better able to limit certain types of ischemic brain damage compared to those which are localized in the cerebral microvasculature. On the other hand, microvascularly-localized agents like tirilazad appear to have better ability to limit BBB damage.

Stereoselective synthesis of Xaa psi[CH2CH(OH)]Yaa dipeptidomimetics and their inclusion in HIV-1 protease inhibitors.

Two stereoselective syntheses of a new pseudodipeptide isostere, the right-hand hydroxyethylene dipeptidomimetic (Xaa psi[CH2CH(OH)]Yaa), are presented. In one method readily available amino acids are used as starting materials for Evans chiral aldol condensation chemistry. The second method relies on the synthesis of an anti-aldol product for the hydroxyethylene isostere via an E-selective ethyl hydrocinnamate enolization, and thus allows for the synthesis of isosteres having side chains other than those available from amino acids. Both methods are illustrated by the chiral synthesis of Boc-Phe psi[CH2CH(OH)]Phe. Two diastereomers, (S,S,R) and (S,R,R), are incorporated into an HIV-1 protease inhibitor template which yields potent inhibitors of HIV-1 protease when the pseudodipeptide isostere is Phe psi[CH(OH)CH2]Phe or Phe psi[CH(OH)CH(OH)]Phe. The resulting Phe psi[CH2CH(OH)]Phe-containing inhibitors possess modest potency.

Novel membrane localized iron chelators as inhibitors of iron-dependent lipid peroxidation.

Attachment of various iron chelating moieties to hydrophobic steroids greatly enhanced their abilities to inhibit iron-dependent lipid peroxidation. Using whole rat brain homogenates, lipid peroxidation initiated by the addition of 200 microM Fe2+ was assessed by the formation of thiobarbituric acid reactive products (TBAR). Under these conditions, 50% inhibitory concentrations of Fe3+ chelators such as desferrioxamine or N1,N8-bis(2,3-dihydroxybenzoyl) spermidine hydrobromide (compound II) were around 170 and 50 microM respectively. Coupling desferrioxamine or compound II to a steroid at the D ring increased their potency in lipid peroxidation assays by 5- to 10-fold. Evidence that inhibition of lipid peroxidation by the steroid-chelator adducts was due to iron chelation was suggested by the fact that methylation of the catechol oxygens of compound II, which are essential for chelation, completely eliminated activity of the steroid adduct. A series of 21-aminosteroids which complex Fe2+ iron and potently inhibit iron-dependent lipid peroxidation has also been synthesized. Coupling Fe2+ chelators to hydrophobic steroids increased their inhibitory potencies by as much as 10- to 100-fold. Some steroid-based Fe2+ chelators stimulated lipid peroxidation at low concentrations in the presence of Fe3+. The degree of stimulation was related to the affinity of a compound for Fe2+ with the stronger chelators causing greater stimulation. The most potent inhibitors of lipid peroxidation in the 21-aminosteroid series were found to be those compounds forming the weakest Fe2+ complexes. The findings suggest that it is iron at or near the membrane that is responsible for the catalysis of lipid peroxidation. The compounds described should provide useful tools for studies of the involvement of iron in the lipid peroxidation process.