The adverse effects of alcohol consumption during pregnancy are known, but the molecular events that lead to the phenotypic characteristics are unclear. To unravel the molecular mechanisms, we have used a mouse model of gestational ethanol exposure, which is based on maternal ad libitum ingestion of 10% (v/v) ethanol for the first 8 days of gestation (GD 0.5-8.5). Early neurulation takes place by the end of this period, which is equivalent to the developmental stage early in the fourth week post-fertilization in human. During this exposure period, dynamic epigenetic reprogramming takes place and the embryo is vulnerable to the effects of environmental factors. Thus, we hypothesize that early ethanol exposure disrupts the epigenetic reprogramming of the embryo, which leads to alterations in gene regulation and life-long changes in brain structure and function. Genome-wide analysis of gene expression in the mouse hippocampus revealed altered expression of 23 genes and three miRNAs in ethanol-exposed, adolescent offspring at postnatal day (P) 28. We confirmed this result by using two other tissues, where three candidate genes are known to express actively. Interestingly, we found a similar trend of upregulated gene expression in bone marrow and main olfactory epithelium. In addition, we observed altered DNA methylation in the CpG islands upstream of the candidate genes in the hippocampus. Our MRI study revealed asymmetry of brain structures in ethanol-exposed adult offspring (P60): we detected ethanol-induced enlargement of the left hippocampus and decreased volume of the left olfactory bulb. Our study indicates that ethanol exposure in early gestation can cause changes in DNA methylation, gene expression, and brain structure of offspring. Furthermore, the results support our hypothesis of early epigenetic origin of alcohol-induced disorders: changes in gene regulation may have already taken place in embryonic stem cells and therefore can be seen in different tissue types later in life.

A total of 164 schoolchildren, aged 11–15 years with high DMF scores was divided into 4 groups. Subjects of the CXF group brushed their teeth after school lunch and rinsed their mouths with a solution containing 0.05% chlorhexidine gluconate + 0.044% NaF in succinic acid/NaOH buffer, pH 5.9. The F group had 0.044% NaF in the buffer. The PI group used a placebo solution and the C group served as the basic control. Respective nonabrasive toothpaste preparations were used in the evenings and twice a day during weekends and the holidays. After 2 years, the mean DMFS increments in the C, Pl, F and CXF groups were 6.3, 5.1, 4.3 and 2.9, respectively. The percentage of subjects with bleeding vestibular gingival units examined in different groups had changed from initial to final value as follows: C, 40–63; PI, 50–49; F, 71–47 and CXF, 63–14.

Luoma, H. et alii: ElTect on caries in mentally handicapped children of addition of fluoride and bicarbonate-phcsphate to dietary sugar products. Scand. J. Dent. Res.ABSTRACT ~ Mentally handicapped children, aged 5-15 years and living in institutions, received fluoride supplement in several sugar products of their diet; in candies, marmalades, jams, fruit juices and in sweet desserts corresponding to 10 mg F as NaF per kg of tlie sugar (sucrose or glucose) of each product. To two of the four daily candies was also added a NaHCO, + KHjPO, mixture (mole ratio 9.8/1, resp.) to substitute for 2.5% of the sugar of the candy. The cotitrol children received the respective products without the additives. After stepwise exclusions of subjects for various reasons, e.g. for the absence of permanent teeth, low initial caries activity, strong medication, Down's syndrome, etc., the mean DMFS-increment in the remaining 43 control subjects was 4.5 and in the 41 test subjects 2.6 lesions/100 surfaces at risk,, i,e. 42% reduction. Caries arrestment had occurred in these test subjects after the first year, while in the respective controls it was continuously increasing. Among numerous oral and body parameters studied, only surface enamel fluoride in primary teeth was increased by the fluoride supplements and urinary phosphate and calcium excretion decreased.

The first component of the mitochondrial electron transport chain is respiratory complex I. Several high‐resolution structures of complex I from different species have been resolved. However, despite these significant achievements, the mechanism of redox‐coupled proton pumping remains elusive. Here, we combined atomistic docking, molecular dynamics simulations, and site‐directed mutagenesis on respiratory complex I from Yarrowia lipolytica to identify a quinone (Q)‐binding site on its surface near the horizontal amphipathic helices of ND1 and NDUFS7 subunits. The surface‐bound Q makes stable interactions with conserved charged and polar residues, including the highly conserved Arg72 from the NDUFS7 subunit. The binding and dynamics of a Q molecule at the surface‐binding site raise interesting possibilities about the mechanism of complex I, which are discussed.