Application of low-rank approximation using truncated singular value decomposition for noise reduction in hyperpolarized 13 C NMR spectroscopy.

Dissolution dynamic nuclear polarization allows in vivo studies of metabolic flux using 13 C-hyperpolarized tracers by enhancing signal intensity by up to four orders of magnitude. The T1 for in vivo applications is typically in the range of 10-50 s for the different 13 C-enriched metabolic substrates; the exponential loss of polarization due to various relaxation mechanisms leads to a strong reduction of the signal-to-noise ratio (SNR). A common solution to the problem of low SNR is the accumulation/averaging of consecutive spectra. However, some limitations related to long delays between consecutive scans occur: in particular, following biochemical kinetics and estimate apparent enzymatic constants becomes time critical when measurement scans are repeated with the typical delay of about 3 T1 . Here we propose a method to dramatically reduce the noise, and therefore also the acquisition times, by computing, via truncated singular value decomposition, a low-rank approximation to the individual complex time-domain signals. Moreover, this approach has the additional advantage that the phase correction can be applied to the spectra already denoised, thus greatly reducing phase correction errors. We have tested the method on (1) simulated data; (2) performing dissolution of hyperpolarized 1-13 C-pyruvate in standard conditions and (3) in vivo data sets, using a porcine model injected with hyperpolarized Na-1-13 C-acetate. It was shown that the presented method reduces the noise level in all the experimental data sets, allowing the retrieval of signals from highly noisy data without any prior phase correction pre-processing. The effects of the proposed approach on the quantification of metabolic kinetics parameters have to be shown by full quantification studies.

Alternating block copolymer-based nanoparticles as tools to modulate the loading of multiple chemotherapeutics and imaging probes.

Cancer therapy often relies on the combined action of different molecules to overcome drug resistance and enhance patient outcome. Combined strategies relying on molecules with different pharmacokinetics often fail due to the lack of concomitant tumor accumulation and, thus, to the loss of synergistic effect. Due to their ability to enhance treatment efficiency, improve drug pharmacokinetics, and reduce adverse effects, polymer nanoparticles (PNPs) have been widely investigated as co-delivery vehicles for cancer therapies. However, co-encapsulation of different drugs and probes in PNPs requires a flexible polymer platform and a tailored particle design, in which both the bulk and surface properties of the carriers are carefully controlled. In this work, we propose a core-shell PNP design based on a polyurethane (PUR) core and a phospholipid external surface. The modulation of the hydrophilic/hydrophobic balance of the PUR core enhanced the encapsulation of two chemotherapeutics with dramatically different water solubility (Doxorubicin hydrochloride, DOXO and Docetaxel, DCTXL) and of Iron Oxide Nanoparticles for MRI imaging. The outer shell remained unchanged among the platforms, resulting in un-modified cellular uptake and in vivo biodistribution. We demonstrate that the choice of PUR core allowed a high entrapment efficiency of all drugs, superior or comparable to previously reported results, and that higher core hydrophilicity enhances the loading efficiency of the hydrophilic DOXO and the MRI contrast effect. Moreover, we show that changing the PUR core did not alter the surface properties of the carriers, since all particles showed a similar behavior in terms of cell internalization and in vivo biodistribution. We also show that PUR PNPs have high passive tumor accumulation and that they can efficient co-deliver the two drugs to the tumor, reaching an 11-fold higher DOXO/DCTXL ratio in tumor as compared to free drugs. STATEMENT OF SIGNIFICANCE: Exploiting the synergistic action of multiple chemotherapeutics is a promising strategy to improve the outcome of cancer patients, as different agents can simultaneously engage different features of tumor cells and/or their microenvironment. Unfortunately, the choice is limited to drugs with similar pharmacokinetics that can concomitantly accumulate in tumors. To expand the spectrum of agents that can be delivered in combination, we propose a multi-compartmental core-shell nanoparticles approach, in which the core is made of biomaterials with high affinity for drugs of different physical properties. We successfully co-encapsulated Doxorubicin Hydrochloride, Docetaxel, and contrast agents and achieved a significantly higher concomitant accumulation in tumor versus free drugs, demonstrating that nanoparticles can improve synergistic cancer chemotherapy.

Myelin-specific T cells carry and release magnetite PGLA-PEG COOH nanoparticles in the mouse central nervous system.

Progress in nanotechnology has determined new strategies concerning drug delivery into the central nervous system for the treatment of degenerative and inflammatory diseases. To date, brain targeting through systemic drug administration, even in a nano-composition, is often unsuccessful. Therefore, we investigated the possibility of loading T lymphocytes with PGLA-PEG COOH magnetite nanoparticles (30 nm), which can be built up to easily bind drugs and monoclonal antibodies, and to exploit the ability of activated T cells to cross the blood-brain barrier and infiltrate the brain parenchyma. Iron oxide nanoparticles have been widely used in biomedical applications due to their theranostic properties and are therefore a well-established nanomaterial. The magnetite core is easily hybridized with polymeric compounds that may enhance the possibility of the nanoparticles entering cells with low phagocytic properties. Taking advantage of these material characteristics, after in vitro assessment of the viability and functionality of nano-loaded MOG35-55 specific T cells, we transferred cells containing the nano-cargo into naïve mice affected by experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. By means of histological and immunohistological methods, we were able to identify the nano-loaded T cells in the central nervous system. Our data demonstrated that T cells containing nanomaterials hold the possibility of carrying and releasing nanoparticles in the brain.

Survival of Coelaenomenodera lameensis (Coleoptera: Chrysomelidae) in Relation to the Physical Characteristics of Different Oil Palm (Elaeis sp.) Breeding Populations.

The edibility of different Elaeis sp. breeding populations present in Benin was tested for the leaf miner Coelaenomenodera lameensis Berti (Coleoptera: Chrysomelidae), a major oil palm pest in Africa. Experiments carried out in sleeves revealed the oviposition capacities of females and the mortality rates for the different developmental stages by comparing the populations found on two breeding populations of Elaeis oleifera (HBK) Cortes, four of Elaeis guineensis Jacquin and four (E. guineensis × E. oleifera) × E. guineensis backcrosses. Females laid their eggs similarly on all breeding populations, with a preference for the E. guineensis La Mé origin. The average hatching rate reached 80% for the La Mé origin as opposed to 28% for the Deli origin. The mortality rates for the larval instars were greater on E. oleifera, on certain backcrosses and on the Deli origin of E. guineensis. Development at the second- and third- larval instars was the most affected, with a mortality rate of three to five times greater than that seen on La Mé. Epidermis and cuticle measurements indicated which breeding populations were suitable or unsuitable for the development of C. lameensis. E. guineensis, with its thin epidermis (12 µm) and cuticle (2 µm), proved to be highly susceptible to C. lameensis attacks. On the other hand, E. oleifera, which is very resistant, exhibited a thicker epidermis (17 µm) and cuticle (4 µm). The breeding populations were thus classified according to the positive or negative influence they exerted on the insect's egg laying and feeding.

Design and optimization of lipid-modified poly(amidoamine) dendrimer coated iron oxide nanoparticles as probes for biomedical applications.

Superparamagnetic iron oxide nanoparticles with a wide size range (2.6-14.1 nm) were synthesized and coated with the amphiphilic poly(amidoamine) PAMAM-C12 dendrimer. The resulting well dispersed and stable water suspensions were fully characterized in order to explore their possible use in biomedical applications. The structural and magnetic properties of the nanoparticles were preserved during the coating and were related to their relaxometric behaviour. The Nuclear Magnetic Resonance Dispersion (NMRD) profiles were found to be in accordance with the Roch model. The biocompatibility was assessed by means of cell viability tests and Transmission Electron Microscopy (TEM) analysis. The nanoparticles' capability of being detected via Magnetic Resonance Imaging (MRI) was investigated by means of clinical MRI scanners both in water and agar gel phantoms, and in a mouse model.

QTL detection by multi-parent linkage mapping in oil palm (Elaeis guineensis Jacq.).

A quantitative trait locus (QTL) analysis designed for a multi-parent population was carried out and tested in oil palm (Elaeis guineensis Jacq.), which is a diploid cross-fertilising perennial species. A new extension of the MCQTL package was especially designed for crosses between heterozygous parents. The algorithm, which is now available for any allogamous species, was used to perform and compare two types of QTL search for small size families, within-family analysis and across-family analysis, using data from a 2 x 2 complete factorial mating experiment involving four parents from three selected gene pools. A consensus genetic map of the factorial design was produced using 251 microsatellite loci, the locus of the Sh major gene controlling fruit shell presence, and an AFLP marker of that gene. A set of 76 QTLs involved in 24 quantitative phenotypic traits was identified. A comparison of the QTL detection results showed that the across-family analysis proved to be efficient due to the interconnected families, but the family size issue is just partially solved. The identification of QTL markers for small progeny numbers and for marker-assisted selection strategies is discussed.

Possible sources of genetic resistance in oil palm (Elaeis guineensis Jacq.) to basal stem rot caused by Ganoderma boninense--prospects for future breeding.

Oil palm estates in southeast Asia suffer from substantial losses due to basal stem rot caused by Ganoderma boninense. Field observations have been carried out in North Sumatra, Indonesia, on a series of planting materials of known origin. Differences in susceptibility to the disease have been detected within the two Elaeis species, guineensis and oleifera. Within Elaeis guineensis, material of Deli origin is highly susceptible compared to material of African origin. It is also possible to detect differences in reaction between parents and between crosses within a given origin. The variability of resistance to basal stem rot within the same cross is also illustrated by the diverse responses of clones derived from palms of the same origin. The prospects opened up by these results are discussed, and the importance of performing an early selection test is highlighted.

MRI of the intracranial corticospinal tracts in amyotrophic and primary lateral sclerosis.

Our aim was to investigate the corticospinal tracts (CST) in motor neurone disease, using MRI, and to correlate findings with clinical data. We studied 31 patients with amyotrophic (ALS) and eight with primary lateral sclerosis (PLS). The signal from the CST was classified into four grades on T2-weighted images, and compared to T2-weighted images of 37 age-matched control subjects. No abnormalities were seen in the CST on T1-weighted images and were rarely evident on proton-density weighting. Variable high signal in the CST was found on T2-weighted images in 35 patients, and in 29 control subjects. Our grades 0 and 1 were more frequent in control subjects, grades 2 and 3 more frequent in patients. We found no correlation between the high signal and clinical data, including the duration of the illness. We therefore conclude that this technique is neither sensitive nor specific except in grade 3 which is quite specific for ALS. In half the patients we found atrophy of the superior parietal gyrus, which merits further study.

Contrast-enhanced magnetisation transfer MRI in metastatic lesions of the brain.

Our purpose was to compare prospectively the sensitivity of contrast-enhanced magnetisation transfer (MT) MRI and gradient-echo (GE) T1-weighted images in metastatic disease of the brain. We studied 52 patients with brain metastases, using conventional T1-weighted GE and MT spin-echo (SE) images after the same standard dose of gadolinium. Axial 5-mm reconstructions of GE data were compared with 5-mm MT images in the same plane. Metastases were counted independently by two neuroradiologists. In 12 patients (23%) MT imaging showed more metastases than GE images (P = 0.03). We detected 68 more metastases with the former technique.

Evaluation of drug use and cost of hospital care for AIDS patients between 1990 and 1994.

This study was designed to evaluate drug use and drug costs of treatment of 1112 AIDS patients at the Infectious Diseases Unit at F. Houphouët Boigny Hospital in Marseilles, France, between January 1, 1990 and December 31, 1994. All drug expenditures directly or indirectly related to AIDS treatment were recorded for both inpatients and outpatients. There were 1952 hospital stays. For each stay baseline characteristics including age, sex risk factors, costs, and duration of hospitalization were noted. Patients were mainly young male drug addicts around thirty years of age. Reason for admission was also noted. The overall number of admissions per year has decreased since 1991 probably due to development of outpatient care. The number of stays per patient per year has decreased since 1993 because of the use of more appropriate therapeutic and prophylactic protocols. The number of drugs used was high increasing from 750 in 1990 to 868 in 1994. Cost of treatment doubled between 1990 and 1994 due to the introduction of many expensive new drugs. Closer analysis showed that the greatest increase in expenditure involved 'antibiotic/antiviral', 'psychiatry/neurology' and 'specialized therapy'. Although not frequently prescribed, costly drugs such as immunoglobulins, hematopoietic growth factors, and parenteral nutrition solutions accounted for a high proportion of total costs. Since AZT, ddI and ddC were used mainly for outpatient treatment, their cost was low in inpatients. Cytomegalovirus-related retinitis, tuberculosis, and multiple infections were cost-intensive complications. The increasing number of cytomegalovirus infections underlines the need for cost evaluation and surveillance of this complication. This study demonstrates that cost of treating AIDS patients is rising due to the use of more and costlier drugs. This finding underlines the need to evaluate and compare new therapeutic modalities in terms of cost effectiveness.

[Evaluation of medication costs in hospitalization of AIDS patients]. / Evaluation du coût médicamenteux des séjours d'hospitalisation chez des malades atteints de sida.

The aim of this study was to examine the global pharmaceutical cost of AIDS patients hospitalized in a ward of infectious diseases in Marseille. They were 209 patients at various clinical stages of HIV infection receiving or not AZT or another specific drugs. All of the 319 hospitalization stays entailed a pharmaceutical cost of 1,065,593 FF for year 1990. A detailed analysis of the therapies, excepted for AZT, determined very large expenses of anti-infectious, hypnotics and other patent drugs of gastroenterology, pneumology, stomatology and toxicology. The study showed that the total drug cost increased with the hospitalization duration.

[Prevalence of gastrocnemius vein insufficiency using color-coded Doppler ultrasound (modifications of the therapeutic strategy)]. / Etude de la prévalence de l'incontinence des veines jumelles par échodoppler couleur (modifications de la stratégie thérapeutique).

The importance of morphologic and dynamic lesions of the gastrocnemius vein is underestimated. Color-coded Duplex scanning was performed in 483 patients with varicosities and 869 legs with some venous abnormalities were discovered. Two types of lesion on gastrocnemius veins were founded: incompetence and dilatation usually located on the medial gastrocnemius vein. In 29.34% of the limbs, a medial gastrocnemius vein incompetence was present and a dilatation in 15.42%. Medial gastrocnemius vein incompetence was associated with a mid calf gastrocnemius communicating vein incompetence in 25%. Physiopathological hypothesis could be drawn of our observations. Gastrocnemius veins when incompetent should be ligated flush to the popliteal vein. The high prevalence of gastrocnemius vein should be considered in the management of varicose veins and color-coded Duplex scanning routinely performed before surgery.