Hybrid nanoreservoirs based on dextran-capped dendritic mesoporous silica nanoparticles for CD133-targeted drug delivery

In this study, the chemical features of dendritic mesoporous silica nanoparticles (DMSNs) provided the opportunity to design a nanostructure with the capability to intelligently transport the payload to the tumor cells. In this regard, doxorubicin (DOX)-encapsulated DMSNs was electrostatically surface-coated with polycarboxylic acid dextran (PCAD) to provide biocompatible dextran-capped DMSNs (PCAD-DMSN@DOX) with controlled pH-dependent drug release. Moreover, a RNA aptamer against a cancer stem cell (CSC) marker, CD133 was covalently attached to the carboxyl groups of DEX to produce a CD133-PCAD-DMSN@DOX. Then, the fabricated nanosystem was utilized to efficiently deliver DOX to CD133+ colorectal cancer cells (HT29). The in vitro evaluation in terms of cellular uptake and cytotoxicity demonstrated that the CD133-PCAD-DMSN@DOX specifically targets HT29 as a CD133 overexpressed cancer cells confirmed by flow cytometry and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. The potentially promising intelligent-targeted platform suggests that targeted dextran-capped DMSNs may find impressive application in cancer therapy.     

Production of ethanol by alginate-entrapped Saccharomyces cerevisiae strain "14-12"

Cells of S. cerevisiae strain "14-12" of different ages were immobilized in sodium alginate and used for conversion of glucose to ethanol. Immobilized cells of 48 hr old were the most potential. Employment of high counts of alginate-entrapped cells shortened the period required for production of the maximal alcohol yield. However, the percentage surviving cells decreased with increasing initial cell counts. Maximal accumulation of ethanol (4.18 g/100 ml) was obtained after 4 days of static fermentation with 1.8 X 10(8) immobilized yeast cells. The residual viable cell count was found to represent 3-fold the surviving percentage in a control experiment using an inoculum of the free yeast cells. Immobilized yeast cells could convert about 85% of the available sugars to ethanol over 28 days of the repeated-batch fermentation. The immobilized cells retained 50% of their viability for 16 days. After 48 days of repeated fermentation only 6% of the yeast cells were viable, and on the 52nd day no viable cells could be detected.     

Digitalis receptor sugar binding site characteristics: A model based upon studies of Na+, K+-ATPase preparations with differing digitalis sensitivities

The structure-activity relationships of the genin moieties of digitalis glycosides are commonly elucidated by determining the inhibitory potency of a variety of genins toward the plasma membrane Na⁺, K⁺-ATPase; qualitatively these relationships appear to be fairly independent of the specific Na⁺, K⁺-ATPase preparation utilized for the analysis. To determine whether this is the case with regard to the sugar moieties of glycosides, the inhibitory effects of 12 monoglycosides of digitoxigenin toward four Na⁺, K⁺-ATPase preparations of different origin were measured. It was found that while recognition of the major structural determinants of sugar activity appeared to be independent of enzyme source, recognition of the minor structural determinants of activity showed some source dependence. It was also observed that the intrinsic sensitivity to sugar potentiation may be source dependent and unrelated to intrinsic sensitivity to inhibition by digitoxigenin. These observations are compatible with a model of the Na⁺, K⁺-ATPase sugar binding site(s) in which intrinsic sensitivity to sugar attachment as well as recognition characteristics (for sugar structural features) both determine the extent to which a sugar moiety may contribute to the activity of monoglycosides. Further, in these studies one of the Na⁺, K⁺-ATPase preparations employed was obtained from rat brain, a tissue known to contain a mixture of ouabain sensitive and insensitive isoforms. We have observed that the rigorous purification techniques employed appear to have selectively removed from or denatured the less ouabain sensitive al isoform found in this enzyme preparation.     

Ethanol tolerance ofSaccharomyces cerevisiae and its relationship to lipid content and composition

Saccharomyces cerevisiae strain 14-12 is a highly ethanol-tolerant organism. It can grow in the presence of 13% ethanol but growth is completely prevented at 14% ethanol. A relationship was detected between yeast lipids and ethanol tolerance. A gradual decrease of lipid content was recorded as the concentration of supplemented ethanol increased. Moreover, free fatty acids were comparatively decreased in these lipid extracts. When separately added to media with 14% ethanol different lipids produced varied stimulatory effects on yeast growth. Maximum yield of yeast growth was obtained at 14% ethanol in the presence of lecithin, palmitic acid and cholesterol. Yeast lipids produced in the presence of these fractions are characterized by a relatively high percentage of free fatty acids. The change in the percentage of free fatty acids was shown to be the controlling factor in ethanol tolerance.     

Antigenic relatedness between human lecithin-cholesterol acyltransferase and phospholipases of the A2 family

A monoclonal antibody, B10, generated against pure human lecithin-cholesterol acyltransferase (EC 2.3.1.43) caused the inhibition of the esterolytic and cholesterol esterifying activities of the enzyme. This antibody also reacted with a number of pancreatic and snake venom phospholipases A2 species but not phospholipase A1. A concentration-dependent inhibition of phospholipase A2 was also seen in the presence of B10. Treatment of lecithin-cholesterol acyltransferase or B10-reacting phospholipases with phenacyl bromide, a reagent known to interact with the active site of phospholipase A2, inhibited both their esterolytic activity and their capacity to bind to B10. A dimeric phospholipase A2 species with a known occluded active site did not cross-react with B10. Thus, lecithin-cholesterol acyltransferase and some enzymes of the phospholipase A2 family share a common antigenic determinant which is probably located near or at their esterolytic active site.     

Studies on the helminth parasites of freshwater fishes of the Sudan

2419 freshwater fishes from the Sudan were examined for helminth parasites and found to harbour one monogenean species, 15 species of adult digenetic trematodes, three species of larval trematodes, 16 species of adult cestodes, 13 species of adult nematodes, two species of larval nematodes and three species of acanthocephalans. Four species of adults and four species of larval worms are recorded for the first time in the Sudan and 30 new hosts are listed. The intensity of infestation of each species, the host-specificity and the variations in the infestation of fishes are discussed. The helminth fauna of the Sudan is compared with that of other African countries.     

Effect of dexamethasone and cytochrome P 450 inhibitors on the formation of 7α-hydroxydehydroepiandrosterone by human adipose stromal cells

7α-Hydroxydehydroepiandrosterone (7α-OHDHA) is a major metabolite of dehydroepiandrosterone (DHA) using adipose stromal cells. To gain a better understanding of the factors regulating DHA metabolism, we examined the effect of dexamethasone and cytochrome P 450 inhibitors on the formation of 7α-OHDHA. Dexamethasone (10⁻⁹ to 10⁻⁷ M) stimulated 7α-OHDHA formation in a dose-dependent manner with a 2- to 5-fold stimulation at 10⁻⁷ M. The dexamethasone stimulated 7α-OHDHA formation was inhibited by RU486 in a dose-dependent manner with suppression to basal levels at 10⁻⁶ M. Progesterone (10⁻⁷ M) had no effect on 7α-OHDHA formation suggesting that the dexamethasone stimulation was acting through the glucocorticoid receptor. Conversion of DHA to 7α-OHDHA was inhibited by ketoconazole and metyrapone. An inhibition of 70–80% was obtained with ketoconazole and 25–60% with metyrapone at concentrations of 10⁻⁵ M. Aminoglutethimide phosphate was less effective than either ketoconazole or metyrapone in inhibiting 7α-OHDHA formation with <30% inhibition at 10⁻⁵ M. These studies indicate that 7-hydroxylation provides an alternative pathway for the metabolism of DHA in peripheral tissues. This pathway, which is regulated by glucocorticoids, may influence the amount of DHA available for conversion to androstenedione and its subsequent aromatization to estrone. The biological role of the 7-oxygenated metabolites and their effects on other steroidogenic pathways have not been established.     

Oxygen mass transfer in a bubble column bioreactor containing lysed yeast suspensions

Summary Liquid-phase volumetric oxygen transfer coefficients were evaluated in a bubble column containing yeast suspensions, using the instationary oxygen absorption method and a polarographic oxygen electrode. The electrode time lag was found to be independent of both the system studied and the operating conditions. The volumetric oxygen mass transfer coefficients k _L a could be reasonably predicted by calculating k _L from the equation derived by Bhavaraju et al. or the empirical equation of Calderbank and Moo-Young and a from the experimental gas hold-up values.Nomenclature a Exponent in Eq.6 or specific gas-liquid interfacial area based on reactor volume m - b Exponent in Eq. 6 - C Constant in Eq 6 or oxygen concentration in the liquid phase g/ml - C ^* Equilibrium oxygen concentration g/ml - C ₀ Oxygen concentration in the liquid phase at t=0 g/ml - C _E Oxygen concentration as determined by the polarographic electrode g/ml - D _B Bubble equivalent diameter mm - D _l Oxygen diffusivity in the liquid phase m²/s - g Acceleration of gravity m/s² - K Consistency index Pasⁿ - K _L Liquid-phase mass transfer coefficient m/s - n Power law exponent - Pe _sw Peclet number based on bubble swarm velocity - S _C Schmidt number - Sh Sherwood number - i Time s - U _B Bubble rise velocity in infinite medium m/s - U _g Superficial air velocity based on column cross-sectional area m/s - U _sw Bubble swarm velocity defined by Eq.15 m/s - Y _MSW Mass transfer coeficient correction factor for mobile interfaces in pseudo-plastic fluids Eq. 7 - Y _MSW Mass transfer coefficient correction factor for immobile interface in pseudo-plastic fluids Eq. 8 Greek letters _l Density of liquid g/ml - _sus Density of unaerated suspension g/ml - _{wet cell} Density of yeast wet cells g/ml - _l Viscosity of the liquid Pas - _app Apparent viscosity of power law fluid Pas - _E Electrode time lag s - _l Time lag due to resistance of the gas-liquid interface s - _g Gas hold-up, volume fraction occupied by the gas phase - _l Liquid hold-up - _c Wet cell volume fraction     

Delayed tumor growth caused by a combined treatment with BCG and Pseudomonas aeruginosa

Summary Sera from mice treated i.v. with 1 mg BCG, followed 14 days later by 0.1 ml (10⁸ killed organisms) of Pseudomonas aeruginosa have shown the capacity to induce tumor necrosis when injected into mice bearing subcutaneous transplants either of a methyl-cholanthrene-induced sarcoma or of the P815 mastocytoma. Furthermore, immunotherapeutic trials were performed in mice bearing a subcutaneous transplanted sarcoma by combining BCG and low doses (0.01 to 0.05 ml) of Pseudomonas. Tumor necrosis was detectable 24 hours later only in the group treated by both BCG and Pseudomonas. In this group, we have also observed a significant decrease of tumor size in comparison with the groups of mice receiving BCG or Pseudomonas alone or no treatment.