Effect of Lactobacillus brevis CD2 containing lozenges and plaque pH and cariogenic bacteria in diabetic children: a randomised clinical trial.

OBJECTIVE: The short-term effect (60 days) of Lactobacillus brevis CD2 lozenges vs placebo on variables related to caries and gingivitis in type 1 diabetic children was evaluated. MATERIAL AND METHODS: Eight diabetics (4-14 years old) were assigned to two groups (n = 34 subjects each), probiotic lozenges and placebo. Stimulated saliva for microbiological analysis and plaque pH were assessed at baseline (t0), 30 days (t1), 60 days (t2) and in the follow-up period (90 days from baseline, t3). Gingival status was assessed at t0, t2 and t3. Two-way ANOVA assessed differences between groups. RESULTS: In the probiotic group, Streptococcus mutans bacterial density mean scores dropped from 3.11 ± 1.13 at baseline to 1.82 ± 0.72 (t2) and to 2.06 ± 0.56 (t3), while in the placebo group, the scores were 3.09 ± 0.8 (t0), 2.82 ± 0.47 (t2) and 3.11 ± 0.43 (t3) (p < 0.01). Lowest and maximum pH fall increased in the probiotic group, from 5.37 ± 0.41 at baseline to 5.49 ± 0.24 at t3 (p < 0.01) and from 1.20 ± 0.46 to 0.98 ± 0.29 (p = 0.02). Bleeding score decreased significantly in both groups, showing a statistically significant lower bleeding score at t2 in the probiotic group (25.6%, 95% CI 21.5-32.7 vs 29.5%, 95% CI 25.2-34.9, p = 0.02). CONCLUSIONS: Lactobacillus brevis CD2 has shown to improve caries-related risk factors and gingival health in diabetic children. CLINICAL RELEVANCE: Lactobacillus brevis CD2 might contribute to improved oral health in type 1 diabetic children.

Oral health status and caries trend among 12-year old Palestine refugee students: results from the UNRWA's oral health surveys 2011 and 2016.

BACKGROUND: In 2016 the United Nation Relief and Work Agency for Palestine refugees in the Near East (UNRWA) commissioned a survey on oral health among 12-year-old students at UNRWA schools in five fields of operation (Jordan, Lebanon, Syria, Gaza Strip and West Bank), following World Health Organization guidelines. The survey aimed to determine the prevalence of dental caries and periodontal diseases among Palestine students attending UNRWA schools and how this has changed over time. METHODS: A two-stage stratified cluster sample design was used. For each Field of operation, the sample size was calculated based on 95% confidence level, 80% power and margin of error of 4%. Clinical examination was carried out by trained Field Oral Health services Officers (FOHSOs) from the 5 fields. Teeth presence and condition, gingival bleeding and calculus and the presence of dental sealants in occlusal surfaces of permanent molars were recorded. Behavior information of students/parents were collected using a questionnaire that was self-completed by the child/parent under supervision. Results were compared with those from a previous survey carried out in 2011 with the same methodology. RESULTS: In the two surveys the distributions of students who had caries experience in their permanent teeth were similar (73.1% in 2011 vs 72.8% in 2016, p = 0.83). In 2016 a significant increase of missing teeth (p < 0.01) and sealants (p < 0.01) was observed. Both surveys have identified behavioral determinants for dental caries, particularly dietary habits such as soft drinks consumption. Gingival health also showed statistical differences among the fields. CONCLUSIONS: The prevalence of caries experience was very high in all fields and, with regard to main oral health indices, no trend of improvement was observed through 2011 and 2016. Surveys' results advocates the need of a large-scale integrated preventive approach toward oral health and the emerging growth of Noncommunicable Diseases (NCDs), in line with the WHO recommendations.

Phosphorodiamidates as a promising new phosphate prodrug motif for antiviral drug discovery: application to anti-HCV agents.

We herein report phosphorodiamidates as a significant new phosphate prodrug motif. Sixty-seven phosphorodiamidates are reported of two 6-O-alkyl 2'-C-methyl guanosines, with significant variation in the diamidate structure. Both symmetrical and asymmetric phosphorodiamidates are reported, derived from various esterified amino acids, both d and l, and also from various simple amines. All of the compounds were evaluated versus hepatitis C virus in replicon assay, and nanomolar activity levels were observed. Many compounds were noncytotoxic at 100 µM, leading to high antiviral selectivities. The agents are stable in acidic, neutral, and moderately basic media and in selected biological media but show efficient processing by carboxypeptidases and efficiently yield the free nucleoside monophosphate in cells. On the basis of in vitro data, eight leads were selected for additional in vivo evaluation, with the intent of selecting one candidate for progression toward clinical studies. This phosphorodiamidate prodrug method may have broad application outside of HCV and antivirals as it offers many of the advantages of phosphoramidate ProTides but without the chirality issues present in most cases.

Substituent effects in benz[a]anthracene carbocations: a stable ion, electrophilic substitution (nitration, bromination), and DFT study.

A series of novel carbocations were generated from isomeric monoalkylated and dialkylated benz[a]anthracenes (BAs) by low-temperature protonation in FSO(3)H/SO(2)ClF. With the monoalkyl derivatives (5-methyl, 6-methyl, 7-methyl, and 7-ethyl) as well as the D-ring methylated analogues (9-methyl, 10-methyl, and 11-methyl), the C-7 or the C-12 protonated carbocations were observed (as the sole or major carbocation) in all cases. Protonation of the 12-methyl derivative (9) gave the C-7 protonated carbocation (9H+) as the kinetic species and the ipso-protonated carbocation (9aH+) as the thermodynamic cation. With the 12-ethyl derivative (10), relief of steric strain in the bay-region greatly favors ipso-protonation (10aH+). With 3,9-dimethyl (14), C-7 protonation (14H+) is strongly favored (with <10% protonation at C-12), and with 1,12-dimethyl (15) the sole species observed is the C-7 protonated carbocation (15H+). For 7-methyl-12-ethyl, 7-ethyl-12-methyl, and 7,12-diethyl derivatives (16, 17, and 18), two ipso-protonated carbocations were initially formed (C-7/C-12), rearranging in time to give the C-12 protonated carbocations exclusively (16aH+, 17aH+, and 18aH+). Protonation outcomes are compared with the computed relative energies by DFT. Charge delocalization paths in the resulting carbocations were deduced based on the magnitude of Deltadelta13C values. For the thermodynamically more stable C-12 protonated carbocations, the charge delocalization path is analogous to those derived based on computed NPA charges for the benzylic carbocations formed by 1,2-epoxide (bay-region) and 5,6-epoxide (K-region) ring opening. Nitration (and bromination) of the 4-methyl, 7-methyl, 7-ethyl, 3,9-dimethyl, and 1,12-dimethyl derivatives resulted in isolation and characterization of several novel derivatives. Excellent agreement is found between low-temperature protonation selectivities and the regioselectivities observed in model substitution reactions.