No abstract

Distance-dependent magnetic resonance tuning (MRET) technology enables the sensing and quantitative imaging of biological targets in vivo, with the advantage of deep tissue penetration and less interactions with the surroundings as compared to fluorescence-based Förster resonance energy transfer (FRET). However, applications of MRET technology in vivo are currently limited by the moderate contrast enhancement and stability of T 1 -based MRET probes. Here we report a new two-way magnetic resonance tuning (t-MRET) nanoprobe with dually activatable T 1 and T 2 magnetic resonance signals that is coupled with dual-contrast enhanced subtraction imaging (DESI). This integrated platform achieves substantially improved contrast enhancement with minimal background signal and can be used to quantitatively image molecular targets in tumours and to sensitively detect very small intracranial brain tumours in patient-derived xenograft models. The high tumour-to-normal tissue ratio offered by t-MRET in combination with DESI provides new opportunities for molecular diagnostics and image-guided biomedical applications.

Background: There is growing evidence to support the beneficial effects of supplementing direct-fed microbials (DFM) on performance, health status, and immune responses of weaned pigs. Therefore, the objective of this study was to investigate dietary supplementation of Bacillus subtilis (DSM 25841) on growth performance, diarrhea, gut permeability and immunity of weaned pigs experimentally infected with a pathogenic F-18 Escherichia coli (E. coli). Results: The F18 E. coli infection reduced (P < 0.05) growth performance and intestinal villi height, whereas increased (P < 0.05) diarrhea and transcellular and paracellular permeability in the jejunum compared with non-challenged control. Supplementation of Bacillus subtilis linearly enhanced average daily gain of E. coli infected pigs from d 0 to 5 post-inoculation (PI) (P < 0.05) and d 0 to 11 PI (P = 0.058). Supplementation of high dose of Bacillus subtilis reduced (P < 0.05) both transcellular and paracellular permeability on d 5 and d 11 PI compared with the E. coli infected pigs fed with control diet. E. coli infection up-regulated (P < 0.05) the mRNA expression of SLC5A10 (soluble carrier family 5 member 10) and MUC2 (mucin 2) on d 5 PI, but down-regulated (P < 0.05) expression of SLC5A10, MUC2, and CLDN1 on d 11 PI in jejunal mucosa when pigs were fed with the control diet. Supplementation of Bacillus subtilis linearly up-regulated (P < 0.05) the mRNA expression of CFTR and ZO1 on d 5 PI and SLC5A10 and MUC2 on d 11 PI in jejunal mucosa of E. coli infected pigs. In addition, E. coli infection increased (P < 0.05) the mRNA expression of several immune genes (IL1A, IL1B, and IL7 on d 5 PI, and IL1B, IL6, IL7, and TNF on d 11 PI) in the ileal mucosa of weaned pigs. Inclusion of Bacillus subtilis to control diet linearly down-regulated gene expression of IL1A on d 5 PI (P = 0.07) and IL6 on d 11 PI (P < 0.05) in ileal mucosa of E. coli infected pigs. Conclusions: Supplementation of Bacillus subtilis (DSM 25841) enhanced growth rate and improved gut barrier function of weaned pigs experimentally infected with a pathogenic E. coli.

A multicentre trial was organized in China as part of an international coordinated research project to study the efficacy and toxicity of single-dose samarium-153 ethylene diamine tetramethylene phosphonate (EDTMP) as a palliative treatment for painful skeletal metastases. One hundred and five patients with painful bone metastases from various primaries were treated with 153Sm-EDTMP at a dose of 37 MBq/kg(group I) or 18.5 MBq/kg (group II). The effects were evaluated according to change in daily analgesic consumption, pain score, sum of effect product (SEP), Physician's Global Assessment (PGA), blood counts, and organ function tests conducted regularly for 16 weeks. Fifty-eight of 70 patients in group I and 30 of 35 in group II had a positive response, with SEPs of 22.29+/-14. 47 and 20.13+/-13.90 respectively. Of 72 patients who had been receiving analgesics, 63 reduced their consumption. PGA showed that the Karnofsky score (KS) increased from 58.54+/-25.90 to 71.67+/-26. 53, indicating improved general condition, but the difference was not significant. Among subgroups of patients, only those with breast cancer showed a significant change in the Karnofsky score after treatment. Inter-group differences were found for net change in KS between patients with lung and patients with breast cancer, and between patients with lung and patients with oesophageal cancer. Seventeen patients showed no response. No serious side-effects were noted, except for falls in the white blood cell (nadir 1.5x10(9)/l) and platelet (nadir 6.0x10(10)/l) counts in 44/105 and 34/105 cases, respectively. Ten patients had an abnormal liver function test. Response and side-effects were both independent of dose. In conclusion, 153Sm-EDTMP provided effective palliation in 83.8% of patients with painful bone metastases; the major toxicity was temporary myelosuppression. Further studies are needed to identify better ways of determining the appropriate dose in the individual case and the efficacy of treatment.