Influence of Drug-to-Lipid Ratio on Drug Release Properties and Liposome Integrity in Liposomal Doxorubicin Formulations

Recent studies have shown that the release properties of vincristine encapsulated in large unilamellar vesicles (LUV) can be regulated by varying the drug-to-lipid (D/L) ratio. In this work it is shown that the drug-to-lipid ratio technique for regulating drug release also applies to doxorubicin encapsulated in LUV. In particular it is shown that the half-times (T_1/2) for doxorubicin release from distearoylphosphatidylcholine (DSPC)/cholesterol LUV in vitro can be increased more than six-fold by increasing the D/L ratio from 0.05 (wt/wt) to 0.39 (wt/wt). This behavior is consistent with the behavior expected for drugs that precipitate following accumulation into liposomes. It is shown that the release properties of ciprofloxacin—a drug that does not precipitate following accumulation into LUV—are not affected by the D/L ratio. It is also shown that the crystalline intravesicular doxorubicin precipitates observed as the D/L ratio is raised from 0.05 to 0.46 adopt increasingly unusual morphologies. Linear crystals are observed at lower D/L values, however triangular and rectangular variations are observed as the D/L ratio is increased, and induce considerable distortion in vesicle morphology. It is noted that trapping efficiency following uptake of external doxorubicin into LUV is reduced from nearly 100% at a D/L ratio of 0.05 (wt/wt) to less than 70% at an (initial) D/L ratio of 0.8 (wt/wt). It is suggested that this arises, at least in part, from membrane-disrupting effects of internal drug crystals as they increase in size.     

Success of a low‐sloping rack for improving downstream passage of silver eels at a hydroelectric plant

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Photosynthetic characteristics and leaf carbon economy of a deciduous and an evergreen dwarf shrub: Vaccinium uliginosum L. and V. vitis-idaea L.

The seasonal course of photosynthetic rate, and light and temperature relations were studied in the dwarf shrubs Vaccinium uliginosum L., deciduous, and Vaccinium vitisidaea L., evergreen, at a subarctic site in northern Sweden, Using the photosynthetic characteristics and meteorological data from the site, the seasonal and life-span carbon dioxide gain was estimated. The photosynthetic capacity of V. uliginosum was at a maximum one month after the start of leaf expansion and declined rapidly in the beginning of September. The old V. vitis-idaea leaves needed about 2 wk to recover full photosynthetic capacity after snow-melt; the current-year V. vitis-idaea leaves needed the same time after bud-break to reach full capacity. The leaves of V. vitis-idaea showed no seasonal trend in photosynthetic capacity after the first two wk of recovery, but their capacity decreased by one third after the first winter and by approximately 10% yr^?1 over the following two yr. The seasonal variation in the photosynthetic response to temperature was more marked in V. uliginosum than in V. vitis-idaea. Light saturation occurred at approximately 3000 μmol m^?2 s^?1 in V. uliginosum and at 60 μmol m^?2 s^?1 in one-year-old V. vitis-idaea leaves. The leaves of both species had a positive carbon balance at photon flux densities above 5 μmol m^?2 s^?1. The calculated seasonal CO² gain was 21 g CO₂ g_?1 leaf in V. uliginosum and 6–8 g CO₂ g_?1 in V. vitis-idaea leaves. Life-span CO₂ gain for leaves of V. vitis-idaea was the same as in V. uliginosum, viz. 21 g CO₂ g_?1. One fifth of the CO₂ gain of V. vitis-idaea was assimilated during periods when V. uliginosum was leafless.     

Location of innervation zone determined with multichannel surface electromyography using an optical flow technique.

Multichannel surface electromyography has developed towards more channels and higher spatial resolution. This allows the study of multichannel electromyograms as images of the potential distribution on the skin. In this paper, a method that estimates the motion of the potential distribution using an optical-flow-based technique is introduced. The optical flow is a vector field that describes how images change with time. The aim of this study was to introduce a new method for innervation zone (IZ) localization and to evaluate its performance. The new method was compared with a method that uses the position of the lowest root-mean-square (RMS) value in an electrode array as an estimate of the IZ localization. Comparisons were made with both simulated signals and with recorded multichannel electromyogram signals. Simulations showed that the methods performed similarly for high signal-to-noise ratio (SNR) and that the optical-flow-based method was superior for lower SNR. When the experimental signals were used, localization with the optical-flow-based method gave a mean absolute deviation of 2.4mm from the location given by an expert group. The lowest RMS method gave a significantly higher deviation (13.6mm). Due to the low computational complexity of the optical flow algorithm it is possible to get the estimations of the IZ localization in real time.     

The effect of biodegradation on surface and bulk property changes of polypropylene,recycled polypropylene and polylactide biocomposites

Biocomposites were subject to exposure to a mixture of fungi and algae in a microenvironment chamber. Surface and bulk property changes of polypropylene/wood flour, recycled polypropylene/cellulose and polylactide/wood flour were monitored by tensile testing, Differential Scanning Calorimetry (DSC), Thermal Gravimetric Analysis (TGA) and Field Emission Scanning Electron Microscope (FE-SEM).All the biocomposites showed a substantial decrease in toughness after 28 and 56 days of hydrolysis. The ductility increased after 28 and 56 days, but deteriorated after 84 days of hydrolysis. Biofilm formation occurred on all biocomposites even if the polymer itself was inert to biodegradation. The microbial colonization affected mainly the surface properties of polypropylene biocomposites while changes were monitored also in the bulk properties of polylactide biocomposites.The cellulose fibres in the composites gave a more easily colonized surface mainly attributed to water uptake. In the short term perspective, the water uptake offered better conditions for biofilm adhesion, and in the longer perspective the exposure to microorganisms also resulted in mechanical degradation, followed by biodegradation of cellulose. With time this will leave a porous matrix of polypropylene, while biodegradable polymers such as polylactide will degrade in parallel with the fibre part.     

Validation of the hepatic portal vein cannulation technique using Atlantic salmon Salmo salar L.

This study assessed the hepatic portal vein cannulation technique and surgical recovery in Atlantic salmon Salmo salar. Haematocrit levels were maintained and blood variables, including cortisol, returned to baseline levels within 1–3 days post-surgery, indicating that this technique is a viable, useful method to study the digestive physiology of fishes.     

Release of acid-soluble radioactivity from rapidly transported proteins in homogenates of rabbit superior colliculus

An intraocular injection of [³H]proline was used to label rabbit retinal ganglion cells including components subjected to axonal transport. Degradation of rapidly axonally transported labelled proteins was estimated in an in vitro system using homogenates of the nerve terminal regions. The energy requirements of this proteolytic process was characterized, as well as the type of enzymatic system. Evidence was obtained for a proteolytic system, active at a neutral pH, which was dependent upon calcium ions and intact sulfhydryl group.     

Effects of increasing amounts of hempseed cake in the diet of dairy cows on the production and composition of milk

This study explored the potential for using seed cake from hemp (Cannabis sativa L.) as a protein feed for dairy cows. The aim was to evaluate the effects of increasing the proportion of hempseed cake (HC) in the diet on milk production and milk composition. Forty Swedish Red dairy cows were involved in a 5-week dose-response feeding trial. The cows were allocated randomly to one of four experimental diets containing on average 494 g/kg of grass silage and 506 g/kg of concentrate on a dry matter (DM) basis. Diets containing 0 g (HC0), 143 g (HC14), 233 g (HC23) or 318 g (HC32) HC/kg DM were achieved by replacing an increasing proportion of compound pellets with cold-pressed HC. Increasing the proportion of HC resulted in dietary crude protein (CP) concentrations ranging from 126 for HC0 to 195 g CP/kg DM for HC32. Further effects on the composition of the diet with increasing proportions of HC were higher fat and NDF and lower starch concentrations. There were no linear or quadratic effects on DM intake, but increasing the proportion of HC in the diet resulted in linear increases in fat and NDF intake, as well as CP intake (P < 0.001), and a linear decrease in starch intake (P < 0.001). The proportion of HC had significant quadratic effects on the yields of milk, energy-corrected milk (ECM) and milk protein, fat and lactose. The curvilinear response of all yield parameters indicated maximum production from cows fed diet HC14. Increasing the proportion of HC resulted in linear decreases in both milk protein and milk fat concentration (P = 0.005 and P = 0.017, respectively), a linear increase in milk urea (P < 0.001), and a linear decrease in CP efficiency (milk protein/CP intake; P < 0.001). In conclusion, the HC14 diet, corresponding to a dietary CP concentration of 157 g/kg DM, resulted in the maximum yields of milk and ECM by dairy cows in this study.     

Negative feedback predominates over cross-regulation to control ERK MAPK activity in response to FGF signalling in embryos

Expression of the gene encoding the MKP-3/Pyst1 protein phosphatase, which inactivates ERK MAPK, is induced by FGF. However, which intracellular signalling pathway mediates this expression is unclear, with essential roles proposed for both ERK and PI(3)K in chick embryonic limb. Here, we report that MKP-3/Pyst1 expression is sensitive to inhibition of ERK or MAPKK, that endogenous MKP-3/Pyst1 co-localizes with activated ERK, and expression of MKP-3/Pyst1 in mice lacking PDK1, an essential mediator of PI(3)K signalling. We conclude that MKP-3/Pyst1 expression is mediated by ERK activation and that negative feedback control predominates in limiting the extent of FGF-induced ERK activity.