Enzymatic activity monitoring through dynamic nuclear polarization in Earth magnetic field.

Cost-effective and portable MRI systems operating at Earth-field would be helpful in poorly accessible areas or in developing nations. Furthermore Earth-field MRI can provide new contrasts opening the way to the observation of pathologies at the biochemical level. However low-field MRI suffers from a dramatic lack in detection sensitivity even worsened for molecular imaging purposes where biochemical specificity requires detection of dilute compounds. In a preliminary spectroscopic approach, it is proposed here to detect protease-driven hydrolysis of a nitroxide probe thanks to electron-nucleus Overhauser enhancement in a home-made double resonance system in Earth-field. The combination of the Overhauser effect and the specific enzymatic modification of the probe provides a smart contrast reporting the enzymatic activity. The nitroxide probe is a six-line nitroxide which lines are shifted according to its substrate/product state, which requires quantum mechanical calculations to predict EPR line frequencies and Overhauser enhancements at Earth field. The NMR system is equipped with a 13-mT prepolarization coil, a 153-MHz EPR coil and a 2-kHz NMR coil. Either prepolarized NMR or DNP-NMR without prepolarization provide NMR spectra within 3 min. The frequency dependence of Overhauser enhancement was in agreement with theoretical calculations. Protease-mediated catalysis of the nitroxide probe could only be measured through the Overhauser effect with 5 min time resolution. Future developments shall open the way for the design of new low-field DNP-MRI systems.

Correction to Comparative Study of Toxicity of Alkoxyamines In Vitro and In Vivo.

The author name M. V. Edeeva should read M. V. Edeleva.

Comparative Study of Toxicity of Alkoxyamines In Vitro and In Vivo.

Effect of alkoxyamines on normal and tumor cells was studied in vitro and in vivo. In vitro experiments showed that alkoxyamines produce a dose-dependent toxic effect on cells of human breast tumor MCF7 line. Transplantation of Krebs-2 ascites carcinoma cells preincubated with alkoxyamines to mice did not induce tumor growth. An opposite effect was observed in normal mouse cells: functional activity of peritoneal macrophages increased. The possibility of using alkoxyamines as theranostic agents is discussed.

Screening for diabetic retinopathy: the first telemedical approach in a primary care setting in France.

OBJECTIVES: Diabetic retinopathy (DR) remains a major cause of visual impairment in France, due to insufficient regular annual screening. Fundus photography is a sensitive alternative to ophthalmoscopy for DR screening. The aim of our study was to report the first telemedical approach to this screening in a primary care setting in France. METHODS: A DR screening centre equipped with a nonmydriatic camera was opened in the 18th district of northern Paris and placed at the disposal of general practitioners (GPs) of the Réseau de Santé Paris Nord (North Paris Health Network). These GPs were invited to send their diabetic patients who had no known DR and had had no fundus examination for more than one year to this screening center. Retinal photographs were taken by an orthoptist without pupillary dilation and sent for grading through the Internet to the Lariboisière Hopital Ophthalmology Department. RESULTS: During an 18-month period, 912 DR screening examinations were performed in 868 diabetic patients referred to the DR screening center by 240 GPs. Patients' mean +/- SD age was 59.9 +/- 11.1 years. Of these 868 patients, 260 (30%) said they never have had an ophthalmological examination. Diabetic retinopathy was detected in 197 patients (22.7%). The proportion of patients for whom fundus photographs of one or both eyes could not be assessed was 10.1%. 159 patients (18.3%) required referral to an ophthalmologist. CONCLUSION: Nonmydriatic photography, combined with teletransmission to a reading centre, proved to be a feasible valid method for the detection of DR. This screening method allowed the identification of patients requiring prompt referral to an ophthalmologist for further complete eye examination.