Campylobacter control measures in indoor broiler chicken: critical re-assessment of cost-utility and putative barriers to implementation.

As campylobacteriosis is one of the most important foodborne infections, a European Union (EU)-27 level cost-effectiveness model has been developed on the socio-economic costs and benefits of applying certain control measures for the reduction of Campylobacter in broiler meat. This is expected to be a gold standard for food safety policymakers in the EU; hence, the validity of its modelling assumptions is essential. The authors of the present paper conducted an independent review of model input parameters on health and economic burden and found that the model most probably overestimated the burden of human campylobacteriosis. A discounted, quality-adjusted life year (QALY)-based European estimate has been developed for human campylobacteriosis and resulted in 15.23 QALY loss per 1000 human gastroenteritis cases. Country-specific cost of illness estimates have been developed for various countries in the EU-27. Based on these model adaptations, a selected Campylobacter control strategy was re-assessed and its high cost-effectiveness was confirmed at the EU level, and also in all but three Member States. Bacteriocin treatment or vaccination of the animals, two alternative control measures were also re-evaluated, and these strategies seemed to be far less cost-effective than the investigated strategy. Putative barriers to the rapid implementation of the investigated Campylobacter control strategy are discussed, and potential solutions are proposed. Further research is required on stakeholder perspectives pertaining to the realistic barriers and implementation opportunities.

Mitochondria respond to Ca2+ already in the submicromolar range: correlation with redox state.

Rapid formation of high-Ca2+ perimitochondrial cytoplasmic microdomains has been shown to evoke mitochondrial Ca2+ signal and activate mitochondrial dehydrogenases, however, the significance of submicromolar cytoplasmic Ca2+ concentrations in the control of mitochondrial metabolism has not been sufficiently elucidated. Here we studied the mitochondrial response to application of Ca2+ at buffered concentrations in permeabilized rat adrenal glomerulosa cells, in an insulin-producing cell line (INS-1/EK-3) and in an osteosarcoma cell line (143BmA-13). Mitochondrial Ca2+ concentration was measured with the fluorescent dye rhod-2 and, using an in situ calibration method, with the mitochondrially targeted luminescent protein mt-aequorin. In both endocrine cell types, mitochondrial Ca2+ concentration increased in response to elevated cytoplasmic Ca2+ concentration (between 60 and 740 nM) and an increase in mitochondrial Ca2+ concentration could be revealed already at a cytoplasmic Ca2+ concentration step from 60-140 nM. Similar responses were observed in the osteosarcoma cell line, although a clearcut response was first observed at 280 nM extramitochondrial Ca2+ only. As examined in glomerulosa cells, graded increases in cytoplasmic Ca2+ concentration were associated with graded increases in the reduction of mitochondrial pyridine nucleotides, consistent with Ca2+-dependent activation of mitochondrial dehydrogenases. Our data indicate that in addition to the recognized role of high-Ca2+ cytoplasmic microdomains, also small Ca2+ signals may influence mitochondrial metabolism.

Stimulus-secretion coupling and mitochondrial metabolism in steroid-secreting cells.

Ca(2+) signal in high-Ca(2+) perimitochondrial microdomains is amplified within the mitochondrial matrix and activates Ca(2+)-dependent dehydrogenases. In steroid-secreting cells, small cytoplasmic Ca(2+) signals may also augment mitochondrial Ca(2+) concentration. The ensuing formation of NADH and NADPH may have an essential role in supporting the increased steroid secretion.

Cytoplasmic Ca2+ at low submicromolar concentration stimulates mitochondrial metabolism in rat luteal cells.

The cytoplasmic Ca2+ signal is transferred to the mitochondrial matrix and activates mitochondrial dehydrogenases. The requirement for supramicromolar cytoplasmic [Ca2+] ([Ca2+]i) in perimitochondrial microdomains in this response has been suggested. We studied the correlation between [Ca2+]i, mitochondrial [Ca2+] ([Ca2+]m) and mitochondrial formation of reduced nicotinamide adenine dinucleotide (phosphate) [NAD(P)H] in the presence of submicromolar [Ca2+]i in cultured rat "large" luteal cells. [Ca2+]i was monitored fluorimetrically with fura-PE3, [Ca2+]m with rhod-2 and NAD(P)H with autofluorescence. In intact cells, prostaglandin F2alpha, which induces both intracellular Ca2+ release and Ca2+ entry, stimulated mitochondrial NAD(P)H formation. Thapsigargin-induced Ca2+ release and subsequent capacitative Ca2+ entry, both resulting in Ca2+ responses not exceeding 150-200 nM, also enhanced the reduction of pyridine nucleotides. As shown in inhibitor studies, the increased steady-state NAD(P)H level was due to activation of Ca2+-dependent dehydrogenases. [Ca2+]m, measured in permeabilized cells, increased moderately, but significantly, following elevation of [Ca2+]i from 50 to 180 nM, showed a further gradual increase at higher submicromolar [Ca2+]i values and rose steeply at supramicromolar [Ca2+]i. In summary, our results demonstrate that, in a steroid-producing cell type, net mitochondrial Ca2+ uptake and mitochondrial dehydrogenation can be activated even by low submicromolar increases of [Ca2+]i.