1H-MRS can monitor metabolites changes of lateral intraventricular BDNF infusion into a mouse model of Alzheimer's disease in vivo.

Proton magnetic resonance spectroscopy (1H-MRS) can provide noninvasive detection of brain metabolite changes in vivo in Alzheimer's disease (AD). AD is a prevalent neurodegenerative disorder characterized by deposition of ß-amyloid peptides (Aß) in multiple brain regions. Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor whose level has been shown to be decreased in AD. BDNF supplementation can offer improvement in AD. However, the means of evaluation are still relatively limited. In the present study, 1H-MRS was applied to evaluate the therapeutic effects of bilateral intraventricular BDNF infusion into APP+PS1 (amyloid precursor protein+presenilin 1) transgenic mice. For comparison to the 1H-MRS changes in the prefrontal cortex, Morris water maze (MWM) test, Fluoro-Jade B staining and immunofluorescence for Aß, glial fibrillary acidic protein and tropomyosin-related kinase B (TrkB) were also performed. Our results showed that N-acetylaspartate (NAA) levels increased and myo-inositol levels decreased in Tg-BDNF mice compared with Tg-PBS mice. But NAA level in Tg-BDNF mice was still lower than that in wild-type mice at 6weeks after infusion. These changes correlated with increased immunoreactivity of TrkB, reduced compact Aß peptide and FJB+ neurons in Tg-BDNF mice compared to Tg-PBS mice. However, Tg-BDNF mice did not present obvious changes in behavior in the MWM. Taken together, we suggest that 1H-MRS may be a sensitive means of evaluating metabolic changes in response to therapeutic strategies in AD. Moreover, BDNF, may be a viable means of offering trophic support during disease.

Promoting positive health behaviours--'tooth worm' phenomenon and its implications.

UNLABELLED: 'Tooth worm' is a traditional belief about the pathogen of dental caries (tooth decay). Nevertheless, in our previous study, parental 'tooth worm' belief was linked to a reduced caries risk of their children. OBJECTIVES: This study aimed to further characterize the impact of parental 'tooth worm' belief on their children's caries experience and its psychobehavioural mechanisms. BASIC RESEARCH DESIGN: analytic observational study. SETTING: Thirteen randomly selected kindergartens in Singapore. PARTICIPANTS: 1,782 preschoolers aged 3-6 years. METHODS: Each child received an oral examination and microbiological tests. Parents completed a self-administered questionnaire on their socio-demographic background, oral health knowledge/attitude and child's oral health habits. RESULTS: Multivariate analysis confirmed a reduced chance of 'high caries rate' (number of affected teeth > 2) among children whose parents held the 'tooth worm' belief (Odds Ratio = 0.41; 95% Confidence Interval = 0.19-0.89). With such perception among parents, children brushed their teeth more frequently (p = 0.042). Since no difference in oral hygiene was observed, the health benefit of the "tooth worm" perception may be acquired through the delivery of fluoride (an agent with proven anti-caries effect) during frequent toothbrushing episodes. CONCLUSIONS: This study revealed a 'tooth worm' phenomenon, indicating that parental 'tooth worm' belief is associated with early establishment of regular toothbrushing habit and reduction of dental caries in children. This phenomenon and its psychobehavioural mechanisms, enriching our understanding of oral health behaviours, have implications for effective health education.

Growth promoting effect of zinc supplementation in infants of high-risk pregnancies.

This study was made to determine whether zinc deficiency is one of the factors involved in growth retardation of infants of high-risk pregnancies. The high risk factors were hypertension of pregnancy, diabetes mellitus, congenital heart disease, chronic nephritis, rheumatic heart disease and hyperthyroidism. 102 neonatal infants were divided into 3 groups: breast fed group, 37 cases; test group, 32 cases formula-fed with supplementary zinc 1.14-2.28 mg/kg/d; and control group, 33 cases formula-fed and supplemented with Vitamin B complex as placebo. The groups were divided by double-blind and randomized method. There were no differences in the 3 groups in sex ratio, growth status and serum zinc concentration at the beginning of the study. Anthropometric data were obtained at 0, 3 and 6 months.

Structure refinement of the chromomycin dimer-DNA oligomer complex in solution.

We have refined the initial docking model of the Mg(II)-co-ordinated chromomycin-d(A2G2C2T2) complex (2 drug equivalents per duplex) by a complete relaxation matrix analysis simulation of the two-dimensional nuclear Overhauser effect (NOESY) spectrum of the complex in 2H2O solution. This relaxation matrix refined structure of the complex exhibits the following characteristics. (1) We observe an unwound and elongated duplex that exhibits characteristics distinct from the A and B-DNA family of helices at the central (G-G-C-C).(G-G-C-C) chromomycin dimer binding and flanking sites. On the other hand sugar puckers, glycosidic torsion angles, displacement of the base-pairs from the helix axis and the minor groove width for this central tetranucleotide segment all fall within the A-family of helical parameters. (2) The chromomycin monomers are aligned in a head-to-tail orientation in the Mg(II)-co-ordinated dimer in the complex. The chromophores are aligned with a slight tilt relative to each other and make an angle of 75 degrees between their planes. The C-D-E trisaccharide segments from individual monomers adopt an extended conformation that projects in opposite directions in the dimer. The divalent metal cation is co-ordinated to the O(1) carbonyl and O(9) enolate atoms of the chromophores and aligns them such that the O(9)-Mg-O(9) angle is 170 degrees while all other O-Mg-O angles are in the 95(+/- 15)degrees range. (3) The sequence specificity of the chromomycin dimer for the widened and shallower (G3-G4-C5-C6).(G3-G4-C5-C6) minor groove binding site is associated with intermolecular hydrogen bonds formed between the OH group at C(8) of the chromophore and the minor groove NH2 group at position 2 and N(3) groups of G4 and between the O(1) oxygen of the E-sugar and the minor groove NH2 group at position 2 of G3 in the complex. (4) Additional intermolecular interactions are primarily van der Waals contacts between anomeric and adjacent CH2 protons on each sugar in the C-D-E trisaccharide segments of the chromomycin dimer and the minor groove surface of the DNA. These results provide insights into the induced conformational transitions required to generate a complementary match between the drug dimer and its DNA binding site on complex formation.

Chromomycin dimer-DNA oligomer complexes. Sequence selectivity and divalent cation specificity.

This paper reports on a solution NMR characterization of the sequence selectivity and metal ion specificity in chromomycin-DNA oligomer complexes in the presence of divalent cations. The sequence selectivity studies have focused on chromomycin complexes with the self-complementary d(A1-A2-G3-G4-C5-C6-T7-T8) duplex containing a pair of adjacent (G3-G4).(C5-C6) steps and the self-complementary d(A1-G2-G3-A4-T5-C6-C7-T8) duplex containing a pair of separated (G2-G3).(C6-C7) steps in aqueous solution. The antitumor agent (chromomycin) and nucleic acid protons have been assigned following analysis of distance connectivities in NOESY spectra and coupling connectivities in DQF-COSY spectra for both complexes in H2O and D2O solution. The observed intermolecular NOEs establish that chromomycin binds as a Mg(II)-coordinated dimer [1 Mg(II) per complex] and contacts the minor-groove edge with retention of 2-fold symmetry centered about the (G3-G4-C5-C6).(G3-G4-C5-C6) segment of the d(A2G2C2T2) duplex. By contrast, complex formation is centered about the (G2-G3-A4-T5).(A4-T5-C6-C7) segment and results in removal of the two fold symmetry of the d(AG2ATC2T) duplex. Thus, the binding of one subunit of the chromomycin dimer at its preferred (G-G).(C-C) site assists in the binding of the second subunit to the less preferred adjacent (A-T).(A-T) site. These observations suggest a hierarchy of chromomycin binding sites, with a strong site detected at the (G-G) step due to the hydrogen-bonding potential of acceptor N3 and donor NH2 groups of guanosine that line the minor groove. The divalent cation specificity has been investigated by studies on the symmetric chromomycin-d(A2G2C2T2) complex in the presence of diamagnetic Mg(II), Zn(II), and Cd(II) cations and paramagnetic Ni(II) and Co(II) cations. A comparative NOESY study of the Mg(II) and Ni(II) symmetric complexes suggests that a single tightly bound divalent cation aligns the two chromomycins in the dimer through coordination to the C1 carbonyl and C9 enolate ions on the hydrophilic edge of each aglycon ring. Secondary divalent cation binding sites involve coordination to the major-groove N7 atoms on adjacent guanosines in G-G steps. This coordination is perturbed on lowering the pH below 6.0, presumably due to protonation of the N7 atoms. The midpoint of the thermal dissociation of the symmetric complex is dependent on the divalent cation with the stability for reversible transitions decreasing in the order Mg(II) greater than Zn(II) greater than Cd(II) complexes.(ABSTRACT TRUNCATED AT 400 WORDS)