Real prevalence of neural tube defects in Japan: How many of such pregnancies have been terminated?

The vital role of folic acid is to reduce the risk of having a neonate afflicted with neural tube defects. The prevalence of neural tube defects (myelomeningocele and anencephaly) has been reported in an incomplete form over the last 40 years in Japan. We aimed to evaluate the total number of neural tube defects including those delivered or terminated, to clarify the proportion of those terminated, and to internationally compare their prevalence. Through information on >311 000 deliveries obtained from 262 hospitals/clinics for 2 years of 2014 and 2015, we identified that the rate of total neural tube defects (termination of pregnancy, live births and stillbirths) was 8.29 per 10 000 deliveries for the year 2014 and was 8.72 for 2015, which were 1.5 and 1.6 times higher than the respective values (live births and stillbirths) reported. It is also observed that the ratio of the total number of myelomeningocele (termination of pregnancy, live births, and stillbirths) to that of anencephaly was approximately 1:1.2, that a half of pregnancies afflicted with neural tube defects were terminated, and that the proportion of termination of pregnancy due to myelomeningocele and due to anencephaly was 20% and 80%, respectively. Internationally, the real prevalence of neural tube defects in Japan was comparatively high, ranking fifth among the seven developed countries. In conclusion, the real prevalence of total neural tube defects was approximately 1.5 times higher than that currently reported by the Japan Association of Obstetricians and Gynecologists.

[Clinical study of levofloxacin 500 mg qd in the treatment of cervicitis and intrauterine infections caused by Chlamydia trachomatis].

The clinical efficacy and safety of levofloxacin (LVFX) 500mg qd were evaluated in female patients with cervicitis with Chlamydia trachomatis and intrauterine infections. LVFX was administered orally at 500 mg qd for 7 days. Bacteriological efficacy was 94.4% (17/18) and clinical efficacy was 100% (16/16) at 14 to 21 days after the end of treatment in cervicitis. On the other hand, bacteriological efficacy and clinical efficacy at the end of treatment in intrauterine infections were 68.8% (11/16) and 94.7% (18/19), respectively. For safety, adverse drug reactions occurred in 9 of 43 patients (20.9%), i.e., increased y-GTP in 2 patients, glucose urine present in 2, and each of all other adverse reactions occurred in 1. All adverse drug reactions observed were either mild or moderate. Results suggested that LVFX 500 mg qd was effective and safe in the treatment of cervicitis with Chlamydia trachomatis and intrauterine infections.

[Efficacy of tosufloxacin in genital chlamydial infections].

According to the 2006 and 2008 "Guidelines for diagnosis and treatment of sexually transmitted diseases" by the Japanese Society for Sexually Transmitted Diseases, quinolones, macrolides and tetracyclines are recommended to treat chlamydial infections. The administration method based on pharmacokinetic/pharmacodynamic theory, as well as the selection of antimicrobial drugs, is important in antimicrobial therapy. It is currently assumed that the efficacy of administering high-dose quinolones once a day is greater than dividing the dose over multiple administrations. To verify the treatment effects of the recommended tosufloxacin dose of 150 mg b.i.d. (300 mg/day) for 7 days, we performed a comparative multicenter open label study of 150 mg b.i.d. and 300 mg q.d. (300 mg/day). The results indicated complete efficacy with 100% (150 mg b.i.d.: 49/49, 300 mg q.d.: 57/57) eradication of Chlamydia trachomatis at both dosages. The clinical efficacy was "markedly effective" in 57.1% (28/49) of cases, "effective" in 42.9% (21/49), and "not effective" in 0% (0/49) in the 150 mg b.i.d. group, while these values were 59.6% (34/57), 40.4% (23/57) and 0% (0/57), respectively, in the 300 mg q.d. group. Quinolone therapy for genital chlamydial infections with tosufloxacin doses of 150 mg b.i.d. was confirmed to be effective as recommended in the guidelines. Moreover, tosufloxacin at 300 mg q.d. was shown to be an effective therapy.

Effects of chemically modified heparin on Chlamydia trachomatis serovar L2 infection of eukaryotic cells in culture.

The mechanism and inhibitors of Chlamydia trachomatis serovar L2 infection of eukaryotic host cells were studied using a tissue culture model infection system. Potent inhibition of infectivity was observed when elementary bodies (EBs) were exposed to heparin or when HeLa 229 cells were treated with heparinase. No significant inhibition was seen the other way around. The same potent inhibition was observed when EBs were exposed to chemically 2-O-desulfated heparin (2-ODS heparin), which is composed of repeating disaccharide units of IdoA-GlcNS(6S), but not when exposed to chemically 6-ODS heparin or completely desulfated and N-resulfated heparin, which is composed of repeating disaccharide units of IdoA(2S)-GlcNS or IdoA-GlcNS, respectively. The inhibitory effects of 2-ODS heparin could be seen only with oligosaccharides longer than dodecasaccharides. The mutant Chinese hamster ovary (CHO) cell line 677, which is deficient in the biosynthesis of heparan sulfate, was less sensitive to C. trachomatis infection than were wild-type CHO cells. F-17 cells, deficient in 2-O-sulfation of heparan sulfate, had the same sensitivity to infection as wild-type CHO cells did. These data suggest that infection of host cells by EBS results from the specific binding of ligand molecules with affinity for heparin on the EB surface to heparan sulfate proteoglycans on the host cell surface. This binding may depend on host cell heparan sulfate chains that are 6-O-sulfated and longer than dodecasaccharides. The 2-ODS heparin oligosaccharides may be a potential agent for the prevention of C. trachomatis infection.