Large Diversity in Nitrogen- and Sulfur-Containing Compatible Solute Profiles in Polar and Temperate Diatoms.

Intense bottom-ice algal blooms, often dominated by diatoms, are an important source of food for grazers, organic matter for export during sea ice melt, and dissolved organic carbon. Sea-ice diatoms have a number of adaptations, including accumulation of compatible solutes, that allows them to inhabit this highly variable environment characterized by extremes in temperature, salinity, and light. In addition to protecting them from extreme conditions, these compounds present a labile, nutrient-rich source of organic matter, and include precursors to climate active compounds (e.g., dimethyl sulfide [DMS]), which are likely regulated with environmental change. Here, intracellular concentrations of 45 metabolites were quantified in three sea-ice diatom species and were compared to two temperate diatom species, with a focus on compatible solutes and free amino acid pools. There was a large diversity of metabolite concentrations between diatoms with no clear pattern identifiable for sea-ice species. Concentrations of some compatible solutes (isethionic acid, homarine) approached 1 M in the sea-ice diatoms, Fragilariopsis cylindrus and Navicula cf. perminuta, but not in the larger sea-ice diatom, Nitzschia lecointei or in the temperate diatom species. The differential use of compatible solutes in sea-ice diatoms suggests different adaptive strategies and highlights which small organic compounds may be important in polar biogeochemical cycles.

Low IL-1alpha expression in bladder cancer tissue and survival.

OBJECTIVE: To investigate whether the previously reported association between IL-1alpha mRNA levels and survival in urinary bladder cancer remains in an extended patient material and to search a mechanism behind a possible antitumoral activity of IL-1alpha. PATIENTS AND METHODS: IL-1alpha mRNA levels were determined in 164 tumors with quantitative TaqMan PCR. RESULTS: A large variation was found in mRNA levels of IL-1alpha. We found, by immunohistochemistry, that IL-1alpha is expressed by tumor rather than stromal cells. In a univariate Cox proportional hazards model, low levels (median split) of IL-1alpha mRNA were associated with a relative hazard ratio (RHR) of 1.7 (95% CI: 1.0-2.9) for cancer-specific death (n=157); a restriction to muscle invasive tumors (n=63) resulted in an RHR of 1.8 (0.9-3.3). In bivariate analyses, adjustment for age, stage and grade respectively, decreased the RHR and the association between IL-1alpha expression and cancer-specific survival was not statistically significant. Which factors to regard as confounders remains unclear. CONCLUSIONS: Low levels of IL-1alpha mRNA expression are associated with an increased risk for cancer-specific death in the investigated material. However, confounding is an issue and to determine whether or not the observed association is causal, we need a defined mechanism and data from other studies.

Immobilisation and evaluation of a vancomycin chiral stationary phase for capillary electrochromatography.

The macrocyclic antibiotic, vancomycin, is covalently bonded to LiChrospher diol silica packed columns and evaluated in capillary electrochromatography (CEC) both in the reversed-phase and polar organic mode. Initially, capillaries were packed with 5 microm LiChrospher 100 A diol silica and evaluated in CEC with a reversed-phase biphenyl-pyrene achiral test resulting in resolution and efficiency values of ca. 2.5 and 100000 plates meter(-1), respectively. Repeatability for this test (resolution and efficiency) was also examined and found to be acceptable for both run-to-run (n=5, 0.74% and 1.5%) and column-to-column (n=5, 3.4% and 9.0%), respectively. Similar results were obtained when the 10 microm LiChrospher 1000 A diol silica was examined with the exception of efficiency, where a reduced plate height value of four times lower was obtained compared to the 100 A material. A simple three step in-situ vancomycin immobilisation procedure was subsequently carried out on these packed diol columns. Selectivity was obtained for thalidomide enantiomers on this vancomycin chiral stationary phase in reversed-phase CEC with resolution and efficiency values of ca. 2.5 and 80000 plates meter(-1), with acceptable repeatability (n=8) 0.9% and 3.0%, respectively. Selectivity was also obtained for thalidomide enantiomers on this phase in the polar organic mode with resolution and efficiency values of ca. 2.5 and 120000 plates meter(-1), with acceptable repeatability (n=7) 0.9% and 2.0%, respectively. It was possible to deduce from a chemometric design carried out for evaluating the mobile phase component effects that organic modifier ratio, MeOH/MeCN, played a significant role in controlling both resolution and efficiency. It was also possible to separate a number of basic analytes including four beta-adrenergic blocking agents in the polar organic mode albeit with lower resolution and efficiency values, ca. 1.5 and 45000 plates meter(-1), respectively.

The use of supercritical fluid extraction for sample preparation of pharmaceutical formulations.

This paper reviews the use of supercritical fluid extraction (SFE) as a sample work-up step in the analysis of drugs in various pharmaceutical formulations. Matrices studies include tablets, animal feed, creams, ointments and infusions. As in other fields of analytical chemistry, SFE has proven to be most suitable for comparatively non-polar compounds in solid matrices. Examples are given however where SFE can also be used, with success, for polar substances or for target compounds present in infusions or other water-based samples. The premise of inverse SFE, i.e. extraction of the matrix instead of the target compound, is discussed.

Evaluation of solubilizers in the drug release testing of hydrophilic matrix extended-release tablets of felodipine.

The drug release of felodipine, a water-insoluble drug, was tested by using sodium lauryl sulphate (SLS), polyoxyethylene 20 sorbitan monooleate (Tween) or cetyltrimethylammonium bromide (CTAB) in the test medium as solubilizers. Three slightly different felodipine extended-release (ER) tablets 10 mg based on the gel matrix principle were evaluated under different solubilizer concentrations, agitation intensities and pH. These tablets were also tested in a bioavailability study together with an oral solution. All three solubilizers substantially enhanced the drug solubility and sink conditions were obtained. The choice of solubilizer affected the drug release rate. This is most probably due to physico-chemical interactions between the gel-forming agent and the solubilizers. All in vitro test conditions provided a good correlation (r2 = 0.94-0.97) to in vivo dissolution, as determined by moment analysis. However, a much steeper in vitro/in vivo relationship was obtained for SLS compared to Tween and CTAB reflecting an inferior discrimination between the tablets by use of this anionic solubilizer.

Flow injection extraction applied to dissolution rate studies of felodipine tablets.

A flow injection analysis (FIA) extraction method has been developed for the analysis of felodipine tablets in connection with dissolution rate testing. The water-soluble oxidation product of felodipine, a pyridine derivative, was extracted into chloroform and measured at 275 nm spectrophotometrically. The FIA-extraction method has been compared with the present liquid chromatographic (LC) method. The sampling rate for the FIA-extraction (60 samples h-1) is 5 times higher than for the LC method. The FIA-extraction method has a standard deviation of 1% for both standards and samples which is the same as for the LC method.