In all infection models rifampicin was most effective at reducing bacterial loads. In the chronic stage, particularly in the in vivo model, many tested compounds lost activity against persisting bacteria and some antibiotics even induced SCV formation.
Ageing has been defined as a global decline in physiological function depending on both environmental and genetic factors. Here we identify gene transcripts that are similarly regulated during physiological ageing in nematodes, zebrafish and mice. We observe the strongest extension of lifespan when impairing expression of the branched-chain amino acid transferase-1 (bcat-1) gene in C. elegans, which leads to excessive levels of branched-chain amino acids (BCAAs). We further show that BCAAs reduce a LET-363/mTOR-dependent neuro-endocrine signal, which we identify as DAF-7/TGFβ, and that impacts lifespan depending on its related receptors, DAF-1 and DAF-4, as well as ultimately on DAF-16/FoxO and HSF-1 in a cell-non-autonomous manner. The transcription factor HLH-15 controls and epistatically synergizes with BCAT-1 to modulate physiological ageing. Lastly and consistent with previous findings in rodents, nutritional supplementation of BCAAs extends nematodal lifespan. Taken together, BCAAs act as periphery-derived metabokines that induce a central neuro-endocrine response, culminating in extended healthspan.
Abbreviations: AUC, area under the curve; FIA, fl ow injection analysis; LPS, lipopolysaccharide; MCAD, medium chain acyl CoA dehydrogenase; PC, phosphatidylcholine; SIRS, systemic infl ammatory response syndrome.
Localized magnetic heating treatments (hyperthermia, thermal ablation) using
superparamagnetic iron oxide nanoparticles continue to be an active area of cancer
research. The present study uses magnetic nanoparticles (MNP) as bimodal tools and
combines magnetically induced cell labelling and magnetic heating. The main focus was to
assess if a selective and higher MNP accumulation within tumour cells due to magnetic
labelling (max. 56 and 83 mT) and consequently a larger heating effect occurs after exposure
to an alternating magnetic field (magnetic heating: frequency 400 kHz, amplitude
24.6 kA m−1) in order to eliminate labelled tumour cells effectively. The results demonstrate
that the magnetically based cellular MNP uptake by human adenocarcinoma
cells is due to suitable magnetic field gradients in vitro which intensify the
temperature increase generated during magnetic heating. A significantly
(P≤0.05) enhanced MNP cell uptake due to 83 mT labelling compared to controls or to 56 mT labelling
was observed. Our experiments required the following conditions, namely a cell concentration of
2.5 × 107 cells ml−1, a minimum MNP
concentration of 0.32 mg Fe ml−1
culture medium, and an incubation time of 24 h, to reach this effect as well as for the
significantly enlarged heating effects to occur.
Localized magnetic heating treatments (hyperthermia, thermal ablation) using superparamagnetic iron oxide nanoparticles (MNPs) continue to be an active area of cancer research. For generating the appropriate heat to sufficiently target cell destruction, adequate MNP concentrations need to be accumulated into tumors. Furthermore, the knowledge of MNP bio-distribution after application and additionally after heating is significant, firstly because of the possibility of repeated heating treatments if MNPs remain at the target region and secondly to study potential adverse effects dealing with MNP dilution from the target region over time. In this context, little is known about the behavior of MNPs after intra-tumoral application and magnetic heating. Therefore, the present in vivo study on the bio-distribution of intra-tumorally injected MNPs in mice focused on MNP long term monitoring of pre and post therapy over seven days using multi-channel magnetorelaxometry (MRX). Subsequently, single-channel MRX was adopted to study the bio-distribution of MNPs in internal organs and tumors of sacrificed animals. We found no distinct change of total MNP amounts in vivo during long term monitoring. Most of the MNP amounts remained in the tumors; only a few MNPs were detected in liver and spleen and less than 1% of totally injected MNPs were excreted. Apparently, the application of magnetic heating and the induction of apoptosis did not affect MNP accumulation. Our results indicate that MNP mainly remained within the injection side after magnetic heating over a seven-days-observation and therefore not affecting healthy tissue. As a consequence, localized magnetic heating therapy of tumors might be applied periodically for a better therapeutic outcome.
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