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In this review, I have discussed current issues related to risk assessments of developmental and reproductive toxicities during the use of pharmaceuticals in pregnant women or women of childbearing potential. Owing to the lack of empirical information on the use of pharmaceuticals (including those approved for the market) in pregnant women, the toxicity of these drugs has been generally evaluated in animal studies. In the case of embryo-fetal developmental (EFD) toxicity, in particular, testingdoi:10.33611/trs.2020-006 fatcat:sazseiiylbh4jcaxigayw52siq
more »... of small-molecule pharmaceuticals in animals (namely rodents and rabbits) is required. The body of research in animal studies affords us an opportunity to explore numerous topics in regulatory science research. However, there are three major issues: risk communication, use of animals, and reduction or deferral of EFD toxicity studies for the development of human pharmaceuticals. Although regulatory science research may not be necessary for some topics, it would contribute to the reduction or replacement of testing in animals. It is hoped that regulatory science research in this field will proceed rapidly, with the goal of safe use of pharmaceuticals for women.
We evaluated the effect of oral aminobenzylpenicillin (OA) for syphilis during pregnancy in terms of treatment duration. Methods: In August 2021, we requested 2,146 obstetrical facilities to provide information on syphilis treatment in pregnant women. Results: There were 45 pregnant women who received OA for active syphilis. Among these women, the median duration of OA treatment was 12 weeks, and four (9%) had been prescribed OA for more than 24 weeks. Conclusion: It takes a long time to adequately treat syphilis with OA during pregnancy.doi:10.14390/jsshp.hrp2022-004 fatcat:6dinch6g4japxnzkv45btv3xoq
The senescence-accelerated mouse (SAM) strain has been established as an inbred strain with an accelerated aging phenotype. SAM prone-8 (SAMP8), one of the SAM strain, exhibits learning disability, immune deficiency, and circadian rhythm loss at a relatively young age. However, it has not been clarified whether aging affects the autonomic nervous activity in SAMP8. The aim of this study was to clarify the utility of SAMP8 in age-related studies of autonomic nervous function. Electrocardiogramdoi:10.1538/expanim.19-0032 pmid:31168043 pmcid:PMC6842801 fatcat:rdupkuaxvjh2bftdp46vvm5i24
more »... CG), body temperature, and locomotor activity were recorded to evaluate bio-behavioral activities. Autonomic nervous activity was evaluated via power spectral analysis of heart rate variability from ECG recordings. SAMP8 significantly decreased both biological and autonomic nervous functions, and the animals exhibited circadian rhythm loss of locomotive activity at as early as 40 weeks of age compared with a control strain at the same age. We concluded that the SAMP8 strain can be used as an animal model for age-related studies of autonomic nervous function.
The current study examined the antimicrobial resistance of Chlamydia trachomatis (CT) genital infection during pregnancy in Japan. We requested 2,146 obstetrical facilities that are members of Japan Association of Obstetricians and Gynecologists to provide information of CT screening tests and antimicrobial resistance in pregnant women between April 2020 and March 2021. The prevalence of CT genital infection in Japan was 2.1%. The antimicrobial resistance was recognized in 2.0 and 2.4% of thedoi:10.3947/ic.2022.0030 pmid:35384428 pmcid:PMC8987183 fatcat:36csphkzmvbp5cduhmeuzcgsqu
more »... ses using azithromycin and clarithromycin, respectively. There were no significant differences in the antimicrobial resistance rate between the 2 analogues (P = 0.28). In Japan, azithromycin and clarithromycin have effectively treated genital CT infections during pregnancy.
In Japan, uterine cancer screening during pregnancy is subsidized by public funds. We examined the current status of the results of cervical cytology conducted during pregnancy in Japan. We requested 2,293 obstetrical facilities to provide information on cervical cytology in pregnant women who delivered between October 2018 and March 2019. A total of 1,292 obstetrical facilities responded, with valid information on a total of 238,743 women. The implementation rate of cervical cytology duringdoi:10.1371/journal.pone.0245282 pmid:33411854 fatcat:gqcpqmnkqjh2vglkdjk36ly4va
more »... gnancy was 86.8% in Japan. The prevalence of abnormal cervical cytology during pregnancy was 3.3% in total and 4.9% using a spatula/brush with liquid-based cytology (LBC). The prevalence of positive high-risk human papillomavirus (HPV) in teenagers with atypical squamous cells of undetermined significance (ASC-US) was significantly higher than women of other ages (p < 0.01). Because HPV vaccine coverage has dropped to less than 1% in Japan, a further study with various conditions will be needed to improve the accuracy of cervical cancer screening during pregnancy.
Sekizawa, Shin-Ichi, Andrew S. French, Ulli Höger, and Päivi H. Torkkeli. Voltage-activated potassium outward currents in two types of spider mechanoreceptor neurons. J. ...doi:10.1152/jn.19188.8.131.5237 pmid:10368410 fatcat:uu45xm6dffarrdx32b6stppctm
Author Contributions Data curation: Shunji Suzuki, Shin-ichi Hoshi, Akihiko Sekizawa. Investigation: Shunji Suzuki. ... Writing -review & editing: Shin-ichi Hoshi, Akihiko Sekizawa, Yoko Sagara, Masanobu Tanaka, Katsuyuki Kinoshita, Tadaichi Kitamura. ), an intravenous injection of ceftriaxone or Citation: Suzuki S, Hoshi ... S-i, Sekizawa A, Sagara Y, Tanaka M, Kinoshita K, et al. (2019) Current status of Neisseria gonorrhoeae cervicitis in pregnant women in Japan. ...doi:10.1371/journal.pone.0211595 pmid:30730922 pmcid:PMC6366733 fatcat:crxrh5s3eng63hkc4evllflxqa
Ishikawa, Teruhiko, Shin-Ichi Sekizawa, Franca B. Sant'Ambrogio, and Giuseppe Sant'Ambrogio. Larynx vs. esophagus as reflexogenic sites for acid-induced bronchoconstriction in dogs. J. Appl. ...doi:10.1152/jappl.19184.108.40.2066 pmid:10194207 fatcat:nvmjp7brhrcxfmezr74szn75c4
Environmental enrichment (EE) can reduce anxiety and stress in experimental animals, while little is known about the influence on autonomic nervous activity especially in disease animal models. Diabetes mellitus (DM) is associated with cardiovascular autonomic dysfunction, which can be characterized by a higher resting heart rate and a lower heart rate variability (HRV). We hypothesized that EE can enhance parasympathetic nervous activity while reducing disease progression in type 2 diabeticdoi:10.1538/expanim.19-0103 pmid:31735765 pmcid:PMC7220714 fatcat:dep5lh5tvrcbthqd64fuv7xabe
more »... e. A telemetry transmitter was implanted in NSY mice to continuously record electrocardiograms (ECG). Animals were kept in a cage with or without a nest box as EE. The autonomic nervous activity was evaluated using power spectral analysis of HRV. Four weeks of EE could increase high frequency (HF) power, but no change was observed in the absence of EE. Although animals showed impaired glucose tolerance at 48 weeks of age regardless of EE, a worsen case was observed in control. These results indicate that EE can be necessary for long-term housing of experimental animals and may reduce the risk of impaired glucose tolerance in NSY mice by enhancing parasympathetic nervous activity. In future, it is demanded whether increasing parasympathetic nervous activity, whatever the method is, can prevent diabetes from worsening.
., Shin-ichi Sekizawa, and Andrew S. French. Inactivation of voltage-activated Na ϩ currents contributes to different adaptation properties of paired mechanosensory neurons. ... et al. 1999) and I Ca (Sekizawa et al. 2000) . ... found (e.g., Höger et al. 1997; Sekizawa et al. 2000) . ...doi:10.1152/jn.2001.85.4.1595 pmid:11287483 fatcat:apyqhtp7jzgwdbejh325vymw6y
Plasticity in the nucleus tractus solitarius and its influence on lung and airway reflexes. The nucleus tractus solitarius (NTS) is the first central nervous system (CNS) site for synaptic contact of the primary afferent fibers from the lungs and airways. The signal processing at these synapses will determine the output of the sensory information from the lungs and airways to all downstream synapses in the reflex pathways. The second-order NTS neurons bring to bear their own intrinsic anddoi:10.1152/japplphysiol.00143.2006 pmid:16484366 fatcat:pbper6y3jfbwloj5l76tizk5ze
more »... ic properties to temporally and spatially integrate the sensory information with inputs from local networks, higher brain regions, and circulating mediators, to orchestrate a coherent reflex output. There is growing evidence that NTS neurons share the rich repertoire of forms of plasticity demonstrated throughout the CNS. This review focuses on existing evidence for plasticity in the NTS, potential targets for plasticity in the NTS, and the impact of this plasticity on lung and airway reflexes. airways; synaptic excitability; intrinsic excitability; brain stem; cough Address for reprint requests and other correspondence: A. C. Bonham, School of Medicine,
In humans, pulse rate variability (PRV) obtained from pulse waves (PWs) is utilized to assess cardiac autonomic nervous function which normally heart rate variability (HRV) obtained from inter-beat (RR) intervals of an electrocardiogram (ECG) recording represents. However, the acceptability of PRV as an index of autonomic function in rats has not been evaluated and, therefore, was the aim of the present study. PW and ECG waveforms of normotensive Sprague Dawley (SD) rats and Spontaneouslydoi:10.33611/trs.2021-001 fatcat:hhc2kpogrnenhkh6srlohf3dq4
more »... ensive Rats (SHR) were recorded using photoplethysmography of the tail and radiotelemetry. The frequency component in a series of intervals between the maximum points of the second derivative photoplethysmography waveform or between the RR intervals of the ECG waveform was analyzed using the Cooley-Tukey fast Fourier transform algorithm and the correlativity of the low frequency (LF) power, high-frequency (HF) power, and LF/HF ratio were determined. The R-values for the coefficients of determination between parameters from HRV and PRV were above 0.98 in both normotensive and hypertensive rats, indicating that these two analyses provide the same results. Our findings suggest that the PRV method may be an alternative to HRV in rats with hypertension to effectively evaluate autonomic nerve function in drug discovery research. Since oscillometric tail-cuff BP analyses in rats are commonly used in pharmaceutical research, the PRV would provide additional valuable information on cardiac autonomic nervous function during the evaluation of drug efficacy and safety. highlights • Frequency analysis of photoplethysmography-derived pulse rates in rats, revealed similar peaks in the HF and LF regions in power spectrum waveforms as those demonstrated in frequency analyses of the RR interval using radiotelemetric ECG recording. • HF, LF, and LF/HF calculated from PRV and HRV showed high correlations, with R-values of the coefficients of determination of ≥0.98 in both normotensive and hypertensive rats. • These findings suggested that PRV analysis obtained from the PW waveform in rats can be an index of autonomic nervous function as well as HRV analysis obtained from the ECG and may be an efficient method for the evaluation of autonomic nerve function in drug discovery research.
In vitro genotoxicity test package of antibiotics for human use submitted to the Japanese regulatory agency during ABSTRACT -The Ames test is used for the mutagenic assessment of drugs; however, it may not provide an accurate genotoxic profile for bactericidal compounds. This study was performed to clarify 1) whether the total number of genotoxicity assays performed (#Assays) was greater during antibiotic development than during the development of other drugs, particularly antivirals, possiblydoi:10.2131/fts.4.241 fatcat:qc3mrowocbc25fr3kdkgrl3m4i
more »... ue to the requirement for additional assessments, 2) whether the maximum doses of the Ames test were less when an alternative assay had been performed for antibiotics, and 3) whether some particular alternative assay had an advantage to minimize #Assays in the last decade. Genotoxicity data submitted to the Pharmaceuticals and Medical Devices Agency in Japan during 2004 -2015 were used. The #Assays was greater and the maximum doses of the Ames tests were lower for antibiotics, which was more obvious when alternative mutagenic assays had been performed. The mouse lymphoma assay or hypoxanthine-guanine phosphoribosyl transferase gene mutation assay was performed preferentially as an alternative. For antibiotic development, preferred genotoxicity test packages should be discussed in the future for a better understanding of the genotoxic potential of antibiotics.
Sekizawa, Shin-ichi and Ann C. Bonham. Group I metabotropic glutamate receptors on second-order baroreceptor neurons are tonically activated and induce a Na ϩ -Ca 2ϩ exchange current. . ...doi:10.1152/jn.00772.2005 pmid:16192328 fatcat:fltrxdopxjgjdlzdzdambyjdrq
Cryopreservation using an aluminum cryo-plate was successfully applied to in vitro-grown carnation (Dianthus caryophyllus L.) shoot tips. The shoot tips (1-1.5 mmϫ1 mm) were dissected from the shoot and precultured at 25°C for 2 days on MS medium containing 0.3 M sucrose. The precultured shoot tips were placed on the aluminum cryo-plate containing ten wells embedded with alginate gel. Osmoprotection was performed by immersing the cryo-plates in loading solution (2 M glycerol and 1.4 M sucrose)doi:10.5511/plantbiotechnology.11.0531a fatcat:suknsdq5kfbnngnxhlte5yncbq
more »... or 90 min at 25°C. Then, dehydration was performed by immersing the cryoplates in PVS2 for 25 min at 25°C. After storage in liquid nitrogen, shoot tips attached to cryoplate, were directly immersed into 2 ml 1 M sucrose solution for regeneration. Using this procedure, the average regrowth level of vitrified shoot tips of 4 carnation cultivars reached 95%. This new method has many advantages and will facilitate the cryostorage of reference cultivars of carnation. Figure 1. The V-Cryo-plate procedure and appearance of in vitro-grown carnation after cryopreservation. (A) Preconditioning of shoot for making uniform material. (B) Aluminium plates and mounting excised shoot tips on the aluminium plates. (C) Hardening of the alginate gel by CaCl 2 solution. (D) Treatment by LS and PVSs for osmo-protection and dehydration using the plates. (E) Uncapped cryotube held on a cryo-cane for immersion in LN. (F) Placing the plates into the cryotubes and directly immersed into LN. (G) Removal the plates from LN and warming them into 2 ml 1 M sucrose solution in a cryotube. (H) Plating the vitrified shoot tips with gel on the medium. (I) Regenerated plantlets 3 days after plating. Bars in photos indicate 1 mm (I), 10 mm (A), 5 mm (B, C, D, E, G, H) and 50 mm (F), respectively.
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