Evaluation of the Safety of Taking Lamotrigine During Lactation Period.

Introduction: Evaluation of the safety of taking lamotrigine (LTG) during lactation in breastfed infants varies according to the information sources. As it is possible that prescribers may avoid prescribing LTG despite of it being one of the essential drugs, more information needs to be accumulated to facilitate its use. Materials and Methods: We retrospectively compared the safety of LTG during the lactation period in 20 pairs of mothers and infants with 20 pairs as the control group. Results: The mean dose of LTG in 20 mothers was 161.1 mg/day (range: 50-400 mg/day). None of the infants showed a neonatal withdrawal syndrome score of 2 or more up to 1 month after delivery. Although drowsiness (n = 3), skin rash (n = 11), jaundice (n = 8), heart murmur (n = 1), poor suckling (n = 1), and retractive breathing (n = 1) were observed in infants, none of these adverse events were serious and the infants recovered. Nineteen of 20 pairs could continue lactation until 1 month after delivery. One pair discontinued breastfeeding because of pain in the mother's nipples. All pairs could continue maternal medication. We then compared the results with those of the control group. There were no significant differences in the presence of adverse events between the LTG and control groups. Conclusion: These data suggest that taking low to moderate doses of LTG during the lactation period might be relatively safe, at least for a period of 1 month after delivery.

Chondroitin sulfate N-acetylgalactosaminyltransferase-1 is required for normal cartilage development.

CS (chondroitin sulfate) is a glycosaminoglycan species that is widely distributed in the extracellular matrix. To understand the physiological roles of enzymes involved in CS synthesis, we produced CSGalNAcT1 (CS N-acetylgalactosaminyltransferase 1)-null mice. CS production was reduced by approximately half in CSGalNAcT1-null mice, and the amount of short-chain CS was also reduced. Moreover, the cartilage of the null mice was significantly smaller than that of wild-type mice. Additionally, type-II collagen fibres in developing cartilage were abnormally aggregated and disarranged in the homozygous mutant mice. These results suggest that CSGalNAcT1 is required for normal CS production in developing cartilage.

Impairment of embryonic cell division and glycosaminoglycan biosynthesis in glucuronyltransferase-I-deficient mice.

We have revealed that in Caenorhabditis elegans, non-sulfated chondroitin is required for normal cell division and cytokinesis at an early developmental stage, whereas heparan sulfate is essential for embryonic morphogenesis in the later stages of development. To clarify the roles of chondroitin sulfate and heparan sulfate in early embryogenesis in mammals, we generated glucuronyltransferase-I (GlcAT-I) knock-out mice by gene targeting. GlcAT-I is an enzyme required for the synthesis of both chondroitin sulfate and heparan sulfate. Here we report that mice with a deletion of GlcAT-I showed remarkable reduction of the synthesis of chondroitin sulfate and heparan sulfate and embryonic lethality before the 8-cell stage because of failed cytokinesis. In addition, treatment of wild-type 2-cell embryos with chondroitinase ABC had marked effects on cell division, although many heparitinase-treated embryos normally developed to blastocysts. Taken together, these results suggest that chondroitin sulfate in mammals, as with non-sulfated chondroitin in C. elegans, is indispensable for embryonic cell division.

Quantification of oligonucleotide containing sequence failure product: comparison of isotope dilution mass spectrometry with other quantification methods.

There is an increasing demand to develop a method for accurate quantification of DNA. Because current methods such as the ultraviolet (UV) absorption-based method are only capable of relative quantification, the quantification result depends completely on the reference material. To achieve accurate quantification of DNA, we have performed isotope dilution mass spectrometry (ID MS)-based quantification of oligonucleotides. We chose a 20-mer synthetic oligonucleotide as the analyte with a longer sequence failure product. Oligonucleotides sometimes contain sequence failure products, which are difficult to remove. It is important to quantify a target product in such mixture. After evaluating the content of the sequence failure product, the analyte spiked with stable isotopically labeled deoxynucleotide monophosphates (dNMPs) was digested by enzyme to its constituent dNMPs or deoxynucleosides, and quantified by liquid chromatography-mass spectrometry. The obtained mass fractions of the 20-mer oligonucleotide showed a good agreement with the results based on phosphate analysis by inductively coupled plasma-optical emission spectrometry and ion chromatography. UV absorption, the general method for DNA quantification, resulted in underestimation. On the other hand, the mass fraction obtained by the gravimetric method was overestimated. This study shows that the ID MS method can determine the precise mass fraction of the target oligonucleotide with the sequence failure product and possesses potential as the primary method for the certification of DNA as a reference material.