Specificity of viscumin revised. As probed with a printed glycan array.

Viscumin, a lectin used in anti-cancer therapy, was originally considered as ßGal recognizing protein; later, an ability to bind 6'-sialyl N-acetyllactosamine (6'SLN) terminated gangliosides was found. Here we probed viscumin with a printed glycan array (PGA) containing a large number of mammalian sulfated glycans, and found a strong binding to glycans with 6-O-SuGal moiety as lactose, N-acetyllactosamine (LN), di-N-acetyllactosamine (LacdiNAc), and even 6-O-SuGalNAcα (but not SiaTn). Also, the ability to bind some of αGal terminated glycans, including Galα1-3Galß1-4GlcNAc, was observed. Unexpectedly, only weak interaction was detected with parent neutral ß-galactosides including LN-LN-LN and branched (LN)2LN oligolactosamines; in the light of these data, one should not confidently classify viscumin as a ß-galactoside-binding lectin. Carrying out PGA in the presence of neutral or sulfated/sialylated glycan, together with sequential elution from lactose-sepharose and consideration of the protein structure, lead to the conclusion that two glycan-binding sites of viscumin have different specificities, one of which prefers charged sulfated and sialylated moieties.

Comparison of the Efficacy and Safety of Ketoprofen Plaster and Diclofenac Plaster for Osteoarthritis-Related Knee Pain: A Multicenter, Randomized, Active-Controlled, Open-Label, Parallel-Group, Phase III Clinical Trial.

PURPOSE: To compare the efficacy and safety of ketoprofen plasters and diclofenac plasters after 3 weeks of administration in patients with osteoarthritis-related knee pain. METHODS: This multicenter, randomized, active-controlled, open-label, parallel-group, noninferiority phase III study randomized 236 adults with osteoarthritis-related knee pain for 3 weeks with ketoprofen plaster 30 mg twice daily (n = 118) or diclofenac plaster 15 mg once daily (n = 118). The primary efficacy end point was the mean change from baseline to week 3 in the mean knee pain intensity score during walking, as measured by a 100-mm visual analog scale with a predefined noninferiority margin of 10.0 mm. Secondary end points included changes in knee pain intensity score during walking (weeks 1 and 2) and at rest (weeks 1, 2, and 3), Knee Injury and Osteoarthritis Outcome Score, Patient Global Impression of Improvement scale assessments, and frequency of rescue medication use after 2 and 3 weeks of treatment. FINDINGS: A total of 223 patients (115 in the ketoprofen group and 108 in the diclofenac group) were included in the per-protocol analysis. After 3 weeks of treatment, the least squares mean change from baseline in knee pain intensity scores during walking was -35.9 (95% CI, -39.7 to -32.2) in the ketoprofen group and -31.7 (95% CI, -35.5 to -27.9) in the diclofenac group, with noninferiority found (least squares mean difference, -4.2; 95% CI, -9.6 to 1.1). Ketoprofen significantly (P < 0.05) reduced the pain intensity score at rest after 2 and 3 weeks of treatment compared with diclofenac. No statistically significant difference was found between the groups in terms of changes in pain intensity score during walking at weeks 1, 2, and 3. The mean Patient Global Impression of Improvement score was statistically significant (P < 0.001) in favor of ketoprofen after 2 and 3 weeks of treatment. In addition, the Knee Injury and Osteoarthritis Outcome Score improved in both groups, and no statistically significant difference was found between the groups in terms of frequency of rescue medication use. The overall adverse event profile of the groups was similar, and no difference was found in skin reaction rates between the 2 groups. IMPLICATIONS: Ketoprofen plasters can be effectively and safely administered to patients with osteoarthritis-related knee pain.

Microbiological aspects of conservative treatment of periodontal disease using gel-based preparations.

The results of epidemiological studies as well as statistical data show that in recent years the dental morbidity rate in the world has remained stable at a high level. Inflammatory diseases of periodontal tissues, in particular generalized forms of periodontitis, reach 80% in the world. The tendency of increasing the prevalence rate of these diseases in Ukraine, 60-99%, is being observed nowadays. AIM: The aim of this study was to examine the antimicrobial activity of three gel-based medicinal products, being widely used in periodontology: Abigel, an herbal remedy, containing fir oil and oak bark extract; Fitoron, which contains oak bark extract, and President gel with chlorhexidine. MATERIALS AND METHODS: Gram-positive and gram-negative bacteria, belonging to different taxonomic groups: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Bacillus subtilis ATCC 6633 and Proteus vulgaris ATCC 4636, Candida albicans ATCC 885-653, were as a substrate for further examinations. Preparing the suspensions of microorganisms with a defined optical density of microbial cells was executed using the turbidity standard (0.5 McFarland standard). The Densi-La-Meter device (made by "PLIVA-Lachema", Czech Republic; wavelength = 540 nm) was used. The suspension was prepared in accordance with the device guidance and the information sheet on innovations in the health care system No. 163-2006 "Standardization of preparation of microbial suspensions". RESULTS: The highest activity against Staphylococcus aureus is being observed in President gel with chlorhexidine (24 mm and 25 mm), followed by Abigel gel (20, 21, 22 mm) and Fitoron has the minimum activity (17 and 18 mm). The growth zone of Bacillus subtilis is maximally inhibited by President gel with chlorhexidine (25 and 26 mm), Fitoron's inhibition zone is of 23 and 24 mm, and in the last place is Abigel gel - 20 and 21 mm. President gel with chlorhexidine has a pronounced antifungal effect with the inhibition zone of 20, 21 and 22 mm, Fitoron's inhibition zone is of 19 and 20 mm, and one of Abigel gel - of 16 and 17 mm. Concerning Enterococcus faecalis, the highest activity was established in President gel with chlorhexidine (the inhibition zone of 22 and 23 mm), Abigel gel had inhibition zone of 20 and 21 mm, whereas one of Fitoron was of 18 and 19 mm. Haemophilus influenzae was maximally influenced by President gel with chlorhexidine with the inhibition zone of 19 and 20 mm, Abigel gel caused the growth inhibition by 17 and 18 mm, and the lowest growth inhibition was of Fitoron - 16 mm. President gel with chlorhexidine (19, 20, 21 mm) and Abigel gel (19 mm) had almost the same influence on the growth of Streptococcus pyogenes, whereas these figures of Fitoron were 16 and 17 mm. Abigel gel had a pronounced activity against Streptococcus mutans with the inhibition zone of 20 mm, one of President gel with chlorhexidine was of 19 and 20 mm, and of Fitoron - 17 and 18 mm. The growth of Neisseria sp was maximally inhibited by President gel with chlorhexidine (18, 19, 20 mm), in the second place was Abigel gel (18, 19 mm) and the lowest results were of Fitoron (16, 17 mm). CONCLUSIONS: President gel with chlorhexidine, Fitoron and Abigel gel have pronounced antimicrobial properties as to the testing cultures of microorganisms under study. Abigel is an effective method of choice in the conservative treatment of inflammatory periodontal diseases.

The bacterial neurometabolic signature of the gut microbiota of young children with autism spectrum disorders.

Introduction. The human gut microbiota is currently seen as an important factor that can promote autism spectrum disorder (ASD) development in children.Aim. This study aimed to detect differences in the taxonomic composition and content of bacterial genes encoding key enzymes involved in the metabolism of neuroactive biomarker compounds in the metagenomes of gut microbiota of children with ASD and neurotypical children.Methodology. A whole metagenome sequencing approach was used to obtain metagenomic data on faecal specimens of 36 children with ASD and 21 healthy neurotypical children of 3-5 years old. Taxonomic analysis was conducted using MetaPhlAn2. The developed bioinformatics algorithm and created catalogue of the orthologues were applied to identify bacterial genes of neuroactive compounds in the metagenomes. For the identification of metagenomic signatures of children with ASD, Wilcoxon's test and adjustment for multiple comparisons were used.Results. Statistically significant differences with decreases in average abundance in the microbiota of ASD children were found for the genera Barnesiella and Parabacteroides and species Alistipes putredinis, B. caccae, Bacteroides intestinihominis, Eubacterium rectale, Parabacteroides distasonis and Ruminococcus lactaris. Average relative abundances of the detected genes and neurometabolic signature approach did not reveal many significant differences in the metagenomes of the groups that were compared. We noted decreases in the abundance of genes linked to production of GABA, melatonine and butyric acid in the ASD metagenomes.Conclusion. For the first time, the neurometabolic signature of the gut microbiota of young children with ASD is presented. The data can help to provide a comparative assessment of the transcriptional and metabolomic activity of the identified genes.

Progressive Generalized Lipodystrophy as a Manifestation of Autoimmune Polyglandular Syndrome Type 1.

We describe APS1 in a boy with generalized lipodystrophy, oral candidiasis, autoimmune hepatitis and adrenal insufficiency. It is the first time when generalized lipodystrophy is associated with APS1.

A new class of organosuperbases, N-alkyl- and N-aryl-1,3-dialkyl-4,5-dimethylimidazol-2-ylidene amines: synthesis, structure, pK(BH+) measurements, and properties.

A series of stable organosuperbases, N-alkyl- and N-aryl-1,3-dialkyl-4,5-dimethylimidazol-2-ylidene amines, were efficiently synthesized from N,N'-dialkylthioureas and 3-hydroxy-2-butanone and their basicities were measured in acetonitrile. The derivatives with tert-alkyl groups on the imino nitrogen were found to be more basic than the tBuP(1) (pyrr) phosphazene base in acetonitrile. The origin of the high basicity of these compounds is discussed. In acetonitrile and in the gas phase, the basicity of the alkylimino derivatives depends on the size of the substituent at the imino group, which influences the degree of aromatization of the imidazole ring, as measured by (13)C NMR chemical shifts or by the calculated ΔNICS(1) aromaticity parameters, as well as on solvation effects. If a wider range of imino-substituents, including electron-acceptor substituents, is treated in the analysis then the influence of aromatization is less predominant and the gas-phase basicity becomes more dependent on the field-inductive effect, polarizability, and resonance effects of the substituent.

Direct observation of the nanoscale dynamics of membrane lipids in a living cell.

Cholesterol-mediated lipid interactions are thought to have a functional role in many membrane-associated processes such as signalling events. Although several experiments indicate their existence, lipid nanodomains ('rafts') remain controversial owing to the lack of suitable detection techniques in living cells. The controversy is reflected in their putative size of 5-200 nm, spanning the range between the extent of a protein complex and the resolution limit of optical microscopy. Here we demonstrate the ability of stimulated emission depletion (STED) far-field fluorescence nanoscopy to detect single diffusing (lipid) molecules in nanosized areas in the plasma membrane of living cells. Tuning of the probed area to spot sizes approximately 70-fold below the diffraction barrier reveals that unlike phosphoglycerolipids, sphingolipids and glycosylphosphatidylinositol-anchored proteins are transiently ( approximately 10-20 ms) trapped in cholesterol-mediated molecular complexes dwelling within <20-nm diameter areas. The non-invasive optical recording of molecular time traces and fluctuation data in tunable nanoscale domains is a powerful new approach to study the dynamics of biomolecules in living cells.

Synthesis and characterization of photoswitchable fluorescent silica nanoparticles.

We have designed and synthesized a new functional (amino reactive) highly efficient fluorescent molecular switch (FMS) with a photochromic diarylethene and a rhodamine fluorescent dye. The reactive group in this FMS -N-hydroxysuccinimide ester- allows selective labeling of amino containing molecules or other materials. In ethanolic solutions, the compound displays a large fluorescent quantum yield of 52 % and a large fluorescence modulation ratio (94 %) between two states that may be interconverted with red and near-UV light. Silica nanoparticles incorporating the new FMS were prepared and characterized, and their spectroscopic and switching properties were also studied. The dye retained its properties after the incorporation into the silica, thereby allowing light-induced reversible high modulation of the fluorescence signal of a single particle for up to 60 cycles, before undergoing irreversible photobleaching. Some applications of these particles in fluorescence microscopy are also demonstrated. In particular, subdiffraction images of nanoparticles were obtained, in the focal plane of a confocal microscope.

Psychological and mental illness among elder immigrants from the former Soviet Union.

The study examined the cultural context of psychological illness among elder immigrants from the former Soviet Union (FSU). Kleinman's (1980) explanatory model of illness and Leininger's theory of culture care (1997) provided the conceptual framework for the study. Participant Observations were conducted in an Adult Day Care Center and Senior Housing. Twenty-three key informants and 10 general informants participated. The social and historical context of the FSU influenced the meaning, attitudes, expressions, and coping strategies toward psychological and mental illness. Cultural stigma influenced the attribution of cause, somatic expression of symptoms, and attitudes toward seeking professional help. Psychological illness was unrecognized, whereas mental illness was viewed as lack of dusha (inner strength and moral character). Group differences were evident with ethnicity as a significant influence in symptom recognition, expression, and attitude toward seeking professional help.