A hetero-alkali-metal version of the utility amide LDA : lithium-potassium diisopropylamide

Designed to extend the synthetically important alkali-metal diisopropylamide [(NPr2)-Pr-i; DA] class of compounds, the first example of a hetero-alkali-metallic complex of DA has been prepared as a partial TMEDA solvate. Revealed by an X-ray crystallographic study, its structure exists as a discrete lithium-rich trinuclear Li2KN3 heterocycle, with TMEDA only solvating the largest of the alkali-metals, with the two-coordinate lithium atoms being close to linearity [161.9(2)degrees]. A variety of NMR spectroscopic studies, including variable temperature and DOSY NMR experiments, suggests that this new form of LDA maintains its integrity in non-polar hydrocarbon solution. This complex thus represents a rare example of a KDA molecule which is soluble in non-polar medium without the need for excessive amounts of solubilizing Lewis donor being added

Accelerated stem cell labeling with ferucarbotran and protamine

To develop and characterize a clinically applicable, fast and efficient method for stem cell labeling with ferucarbotran and protamine for depiction with clinical MRI. The hydrodynamic diameter, zeta potential and relaxivities of ferucarbotran and varying concentrations of protamine were measured. Once the optimized ratio was found, human mesenchymal stem cells (MSCs) were labeled at varying incubation times (1–24 h). Viability was assessed via Trypan blue exclusion testing. 150,000 labeled cells in Ficoll solution were imaged with T1-, T2- and T2*-weighted sequences at 3 T, and relaxation rates were calculated. Varying the concentrations of protamine allows for easy modification of the physicochemical properties. Simple incubation with ferucarbotran alone resulted in efficient labeling after 24 h of incubation while assisted labeling with protamine resulted in similar results after only 1 h. Cell viability remained unaffected. R2 and R2* relaxation rates were drastically increased. Electron microscopy confirmed intracellular iron oxide uptake in lysosomes. Relaxation times correlated with results from ICP-AES. Our results show internalization of ferucarbotran can be accelerated in MSCs with protamine, an approved heparin antagonist and potentially clinically applicable uptake-enhancing agent

Distribution and Habitat Associations of Billfish and Swordfish Larvae across Mesoscale Features in the Gulf of Mexico

Ichthyoplankton surveys were conducted in surface waters of the northern Gulf of Mexico (NGoM) over a three-year period (2006–2008) to determine the relative value of this region as early life habitat of sailfish (Istiophorus platypterus), blue marlin (Makaira nigricans), white marlin (Kajikia albida), and swordfish (Xiphias gladius). Sailfish were the dominant billfish collected in summer surveys, and larvae were present at 37.5% of the stations sampled. Blue marlin and white marlin larvae were present at 25.0% and 4.6% of the stations sampled, respectively, while swordfish occurred at 17.2% of the stations. Areas of peak production were detected and maximum density estimates for sailfish (22.09 larvae 1000 m−2) were significantly higher than the three other species: blue marlin (9.62 larvae 1000 m−2), white marlin (5.44 larvae 1000 m−2), and swordfish (4.67 larvae 1000 m−2). The distribution and abundance of billfish and swordfish larvae varied spatially and temporally, and several environmental variables (sea surface temperature, salinity, sea surface height, distance to the Loop Current, current velocity, water depth, and Sargassum biomass) were deemed to be influential variables in generalized additive models (GAMs). Mesoscale features in the NGoM affected the distribution and abundance of billfish and swordfish larvae, with densities typically higher in frontal zones or areas proximal to the Loop Current. Habitat suitability of all four species was strongly linked to physicochemical attributes of the water masses they inhabited, and observed abundance was higher in slope waters with lower sea surface temperature and higher salinity. Our results highlight the value of the NGoM as early life habitat of billfishes and swordfish, and represent valuable baseline data for evaluating anthropogenic effects (i.e., Deepwater Horizon oil spill) on the Atlantic billfish and swordfish populations

An Efficient Targeted Drug Delivery through Apotransferrin Loaded Nanoparticles

BACKGROUND: Cancerous state is a highly stimulated environment of metabolically active cells. The cells under these conditions over express selective receptors for assimilation of factors essential for growth and transformation. Such receptors would serve as potential targets for the specific ligand mediated transport of pharmaceutically active molecules. The present study demonstrates the specificity and efficacy of protein nanoparticle of apotransferrin for targeted delivery of doxorubicin. METHODOLOGY/PRINCIPAL FINDINGS: Apotransferrin nanoparticles were developed by sol-oil chemistry. A comparative analysis of efficiency of drug delivery in conjugated and non-conjugated forms of doxorubicin to apotransferrin nanoparticle is presented. The spherical shaped apotransferrin nanoparticles (nano) have diameters of 25-50 etam, which increase to 60-80 etam upon direct loading of drug (direct-nano), and showed further increase in dimension (75-95 etam) in conjugated nanoparticles (conj-nano). The competitive experiments with the transferrin receptor specific antibody showed the entry of both conj-nano and direct-nano into the cells through transferrin receptor mediated endocytosis. Results of various studies conducted clearly establish the superiority of the direct-nano over conj-nano viz. (a) localization studies showed complete release of drug very early, even as early as 30 min after treatment, with the drug localizing in the target organelle (nucleus) (b) pharmacokinetic studies showed enhanced drug concentrations, in circulation with sustainable half-life (c) the studies also demonstrated efficient drug delivery, and an enhanced inhibition of proliferation in cancer cells. Tissue distribution analysis showed intravenous administration of direct nano lead to higher drug localization in liver, and blood as compared to relatively lesser localization in heart, kidney and spleen. Experiments using rat cancer model confirmed the efficacy of the formulation in regression of hepatocellular carcinoma with negligible toxicity to kidney and liver. CONCLUSIONS: The present study thus demonstrates that the direct-nano is highly efficacious in delivery of drug in a target specific manner with lower toxicity to heart, liver and kidney

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening