Demonstration of discrete secreted and membrane-bound ocular mucins in the dog

Our aims were to separate and characterize secreted canine ocular mucins, and to provide definitive evidence of membrane-bound mucins at the canine ocular surface. Mucus was collected by suction from the ocular surface of normal dogs and dispersed in guanidine hydrochloride and a cocktail of protease inhibitors. Caesium chloride density gradient centrifugation separated secreted mucins from membranes, which were collected from the top of the gradients. Membranes were extracted with octyl glucoside and screened using lectins and anti-mucin antibodies. Gradient fractions containing secreted mucins were constituted into pools on the basis of differential lectin and antibody staining. High molecular weight material from each pool was purified by gel filtration. This material, and the membrane extract, were reduced and alkylated. Vacuum blotting of separated materials after agarose gel electrophoresis was used to compare subunit structure. Density gradient profiles indicated three principal secreted glycoprotein peaks: one staining strongly with anti-mucin antibodies. Gel filtration demonstrated that each contained high molecular weight material. Vacuum blots demonstrated the presence of two secreted glycoproteins with differently sized subunits. On the basis of buoyant density, one of these may be lipid complexed. Membrane extracted material stained with anti-mucin antibodies, and vacuum blotting of this material provided evidence for two membrane-bound components. In conclusion, we have shown that normal canine ocular mucus contains two secreted mucins, each exhibiting different subunit structure; one of these mucins may undergo lipid complexation. Normal canine ocular mucus also contains two membrane-bound mucins: one of which is unique among membrane mucins in showing subunit structure.     

Genotoxic effect of triarylmethane dye--acid green 16 after chronic ethanol consumption in mice

Genotoxic effect and hepatic microsomal monooxygenase activities were assessed in mice treated with Acid Green 16 (single i.p. injection at dose 75 mg/kg) superimposed on prolonged ethanol consumption (10% solution in drinking water for 2-4 months). Treatment of mice with Acid Green 16 led to an increased frequency of micronucleated erythrocytes in bone marrow. In animals pretreated with ethanol the frequency of micronucleated erythrocytes, produced by Acid Green 16, was significantly higher. The changes in frequency of micronucleated erythrocytes were accompanied by the enhanced activity of microsomal monooxygenases manifested by higher activity of 7-ethoxycoumarin o-deethylase (the level of cytochrome P-450 was not altered). The obtained results showed that ethanol tended to increase the genotoxic effect of Acid Green 16. However, the slight inductive effect of ethanol on microsomal monooxygenases did not provide clear evidence that the genotoxic effect of Acid Green 16 was associated with ethanol stimulation of the metabolic activation of the dye in the liver.     

Antitumor Organometallics. IV. The Mutagenic Potential of Some Diphenylantimony(III) Dithiophosphorus Derivatives

Two diphenylantimony(III) derivatives of dithiophosphorus ligands, i.e. Ph(2)SbS(2)PPh(2) and Ph(2)SbS(2)P(OPr-i)(2), which were previously found to exhibit antitumor properties, have been now investigated for potential mutagenic effects in healthy and Ehrlich ascites tumor-bearing mice. Two short-term tests, i.e. the micronucleus test and the cytogenetic analysis, were used as end-points for mutagenicity. The results are consistent with a mutagenic potential for both organoantimony(III) compounds tested, the effect being higher for the phosphorodithioato derivative.     

Biosynthesis of progesterone derived neurosteroids by developing avian CNS: in vitro effects on the GABAA receptor complex

Although enthusiasm for measuring health-related quality of life (HRQL) in clinical trials exists, information is limited on the meaning of scores. We examined the relation between scores from the 34-item Medical Outcomes Study HIV Health Survey (MOS-HIV) and the more detailed HIV Overview of Problems-Evaluation System (HOPES) using the responses of 318 HIV-infected outpatients being treated in Los Angeles and Baltimore. With the HOPES problem statements as independent variables, statistically significant predictors of the variation in MOS-HIV scores for the Physical Function, Mental Health, and Energy/Fatigue scales were identified using stepwise regression. Approximately 60% to 70% of the variation in each of the scores was explained by five to seven different HOPES problem statements, with a single item explaining 47% to 59% of the variation. We created illustrative profiles for each of the three MOS-HIV scales using the HOPES items identified in the regressions. Independent of the scale, persons scoring in the top MOS-HIV quartile tended to report few if any problems, whereas a decline in score to the next quartile was characterized by functional difficulties (e.g., "HIV interferes with work"). The onset of specific problems might trigger further evaluation and potential intervention from health care providers to help maintain patient functioning.     

p-Coumaric acid,Kaempferol, Astragalin and Tiliroside Influence the Expression of Glycoforms in AGS Gastric Cancer Cells

Abnormal glycosylation of cancer cells is considered a key factor of carcinogenesis related to growth, proliferation, migration and invasion of tumor cells. Many plant-based polyphenolic compounds reveal potential anti-cancer properties effecting cellular signaling systems. Herein, we assessed the effects of phenolic acid, p-coumaric acid and flavonoids such as kaempferol, astragalin or tiliroside on expression of selected cancer-related glycoforms and enzymes involved in their formation in AGS gastric cancer cells. The cells were treated with 80 and 160 µM of the compounds. RT-PCR, Western blotting and ELISA tests were performed to determine the influence of polyphenolics on analyzed factors. All the examined compounds inhibited the expression of MUC1, ST6GalNAcT2 and FUT4 mRNAs. C1GalT1, St3Gal-IV and FUT4 proteins as well as MUC1 domain, Tn and sialyl T antigen detected in cell lysates were also lowered. Both concentrations of kaempferol, astragalin and tiliroside also suppressed ppGalNAcT2 and C1GalT1 mRNAs. MUC1 cytoplasmic domain, sialyl Tn, T antigens in cell lysates and sialyl T in culture medium were inhibited only by kaempferol and tiliroside. Nuclear factor NF-κB mRNA expression decreased after treatment with both concentrations of kaempferol, astragalin and tiliroside. NF-κB protein expression was inhibited by kaempferol and tiliroside. The results indicate the rationality of application of examined polyphenolics as potential preventive agents against gastric cancer development.     

E-business technologies for xRM: Exploring the readiness of public broadcasters

This paper examines the possibilities of enhancing relationship management between public service broadcasters and their stakeholders by harnessing the potential of newest e-business technologies and concepts, such as: social media, digital and interactive TV, and mobile computing. In order to facilitate adoption of relationship management strategy, a framework for leveraging relationship management is proposed. Evaluation was performed within the e-business system of a public broadcaster. This empirical study explored the readiness and expected benefits of relationship management implementation. The research results have indicated that a public broadcaster could achieve a higher level of social responsibility, improve business sustainability, and empower communication and collaboration with all the stakeholders by using emerging technologies for relationship management activities.     

Origin of Violet‐Blue Emission in Ti‐Doped Gahnite

ZnAl₂O₄ doped with Ti⁴⁺ (2%) was synthesized by the hydrothermal method at 220°C at pressure of 25 bars. An average grain size of the as‐prepared sample was 3 nm, the samples with biggest grain size were obtained after annealing at 300°C, 500°C, 600°C, 700°C, and 900°C, diameter of the latter was about 33 nm. IR spectroscopy indicated that ZnAl₂O₄ was partially inverted. The degree of the inversion decreases with increase in the annealing temperature but increases with increasing Ti⁴⁺ content. Absorption and emission spectra as well as emission decay profiles were recorded at 300 and 77 K. The observed spectra are due to charge‐transfer O^2??Ti⁴⁺ transitions. Color of the emission depends on the nanocrystal size and with increase in its diameter changes from violet to blue, accordingly the absorption bands exhibit redshift. The calculations based on Density Functional Theory confirmed the experimental results. 3d electrons of titanium ions form the bottom of the ZnAl₂O₄:Ti⁴⁺ conduction band, oxygen, aluminum or zinc vacancies create additional levels in the gahnite energy band gap. It was also found that in ZnAl₂O₄ aluminum or zinc vacancy induces magnetism with relatively high magnetic moment close to 1 μ_B per vacancy.     

Curcumin and Weight Loss: Does It Work?

Obesity is a global health problem needing urgent research. Synthetic anti-obesity drugs show side effects and variable effectiveness. Thus, there is a tendency to use natural compounds for the management of obesity. There is a considerable body of knowledge, supported by rigorous experimental data, that natural polyphenols, including curcumin, can be an effective and safer alternative for managing obesity. Curcumin is a is an important compound present in Curcuma longa L. rhizome. It is a lipophilic molecule that rapidly permeates cell membrane. Curcumin has been used as a pharmacological traditional medicinal agent in Ayurvedic medicine for ∼6000 years. This plant metabolite doubtless effectiveness has been reported through increasingly detailed in vitro, in vivo and clinical trials. Regarding its biological effects, multiple health-promoting, disease-preventing and even treatment attributes have been remarkably highlighted. This review documents the status of research on anti-obesity mechanisms and evaluates the effectiveness of curcumin for management of obesity. It summarizes different mechanisms of anti-obesity action, associated with the enzymes, energy expenditure, adipocyte differentiation, lipid metabolism, gut microbiota and anti-inflammatory potential of curcumin. However, there is still a need for systematic and targeted clinical studies before curcumin can be used as the mainstream therapy for managing obesity.     

Cyclin-Dependent Kinase Synthetic Lethality Partners in DNA Damage Response

Cyclin-dependent kinases (CDKs) are pivotal mediators and effectors of the DNA damage response (DDR) that regulate both the pathway components and proteins involved in repair processes. Synthetic lethality (SL) describes a situation in which two genes are linked in such a way that the lack of functioning of just one maintains cell viability, while depletion of both triggers cell death. Synthetic lethal interactions involving CDKs are now emerging, and this can be used to selectively target tumor cells with DNA repair defects. In this review, SL interactions of CDKs with protooncogene products MYC, poly (ADP-ribose) polymerase (PARP-1), and cellular tumor antigen p53 (TP53) are discussed. The individual roles of each of the SL partners in DDR are described.