Associations between intensive diabetes therapy and NMR-determined lipoprotein subclass profiles in Type 1 diabetes

Our objective is to define differences in circulating lipoprotein subclasses between intensive vs. conventional management of Type 1 diabetes during the randomization phase of the Diabetes Control and Complications Trial (DCCT). Nuclear magnetic resonance-determined lipoprotein subclass profiles (NMR-LSP), which estimate molar subclass concentrations and mean particle diameters, were determined in 1,294 DCCT subjects after a median of five (interquartile range: four, six) years following randomization to intensive or conventional diabetes management. In cross-sectional analyses, we compared standard lipids and NMR-LSP between treatment groups. Standard total-, LDL- and HDL-cholesterol levels were similar between randomization groups, while triglyceride levels were lower in the intensively treated group. NMR-LSP showed that intensive therapy was associated with larger LDL diameter (20.7 vs. 20.6 nm, p=0.01) and lower levels of small LDL (median: 465 vs. 552 nmol/l, p=0.007), total IDL/LDL (mean: 1000 vs. 1053 nmol/l, p=0.01), and small HDL (mean: 17.3 vs. 18.6 μmol/l, p<0.0001), the latter accounting for reduced total HDL (mean: 33.8 vs. 34.8 μmol/l, p=0.01). In conclusion, intensive diabetes therapy was associated with potentially favorable changes in LDL and HDL subclasses in sera. Further research will determine whether these changes contribute to the beneficial effects of intensive diabetes management on vascular complications.

Identification and validation of the dopamine agonist bromocriptine as a novel therapy for high-risk myelodysplastic syndromes and secondary acute myeloid leukemia

Myelodysplastic syndromes (MDS) represent a broad spectrum of diseases characterized by their clinical manifestation as one or more cytopenias, or a reduction in circulating blood cells. MDS is predominantly a disease of the elderly, with a median age in the UK of around 75. Approximately one third of MDS patients will develop secondary acute myeloid leukemia (sAML) that has a very poor prognosis. Unfortunately, most standard cytotoxic agents are often too toxic for older patients. This means there is a pressing unmet need for novel therapies that have fewer side effects to assist this vulnerable group. This challenge was tackled using bioinformatic analysis of available transcriptomic data to establish a gene-based signature of the development and progression of MDS. This signature was then used to identify novel therapeutic compounds via statistically-significant connectivity mapping. This approach suggested re-purposing an existing and widely-prescribed drug, bromocriptine as a novel potential therapy in these disease settings. This drug has shown selectivity for leukemic cells as well as synergy with current therapies.

Prostate cancer radiotherapy: potential applications of metal nanoparticles for imaging and therapy

Prostate cancer (CaP) is the most commonly diagnosed cancer in males. There have been dramatic technical advances in radiotherapy delivery, enabling higher doses of radiotherapy to primary cancer, involved lymph nodes and oligometastases with acceptable normal tissue toxicity. Despite this, many patients relapse following primary radical therapy, and novel treatment approaches are required. Metal nanoparticles are agents that promise to improve diagnostic imaging and image-guided radiotherapy and to selectively enhance radiotherapy effectiveness in CaP. We summarize current radiotherapy treatment approaches for CaP and consider pre-clinical and clinical evidence for metal nanoparticles in this condition.

Prostate cancer (CaP) is the most commonly diagnosed cancer in males and is responsible for more than 10,000 deaths each year in the UK.1 Technical advances in radiotherapy delivery, including image-guided intensity-modulated radiotherapy (IG-IMRT), have enabled the delivery of higher radiation dose to the prostate, which has led to improved biochemical control. Further improvements in cancer imaging during radiotherapy are being developed with the advent of MRI simulators and MRI linear accelerators.2–4

Nanotechnology promises to deliver significant advancements across numerous disciplines.5 The widest scope of applications are from the biomedical field including exogenous gene/drug delivery systems, advanced biosensors, targeted contrast agents for diagnostic applications and as direct therapeutic agents used in combination with existing treatment modalities.6–11 This diversity of application is especially evident within cancer research, with a myriad of experimental anticancer strategies currently under investigation.

This review will focus specifically on the potential of metal-based nanoparticles to augment the efficacy of radiotherapy in CaP, a disease where radiotherapy constitutes a major curative treatment modality.12 Furthermore, we will also address the clinical state of the art for CaP radiotherapy and consider how these treatments could be best combined with nanotherapeutics to improve cancer outcomes.

Association of a Mediterranean type diet with age-related macular degeneration in the EUREYE study

Investigative Ophthalmology & Visual Science Volume 56 Issue 7 Pages 3760-3760