To examine in detail spinal nerve defects induced by prenatal exposure to valproic acid in mice, pregnant ICR mice were subcutaneously injected with a single dose of 400 mg/kg valproic acid on gestational day 6, 7, 8, or 9, and their embryos were observed on gestational day 10. The whole-mount immunostaining using an anti-neurofilament antibody allowed us to identify spinal nerve defects, such as a loss of bundle, anastomosis among bundles arising from adjacent segment, and a disrupted segmental pattern of the dorsal root ganglia, in valproic acid-exposed embryos. The prevalence of spinal nerve defects was the highest in the embryos exposed to valproic acid on gestational day 8 among the experimental groups. Then, effects of the administration dose of valproic acid on the prevalence of spinal nerve defects were examined on gestational day 10 and found to be dose-dependently increased. It was noteworthy that all embryos exposed to 600 mg/kg of valproic acid on gestational day 8 suffered spinal nerve defects. Folic acid (3 mg/kg/day) supplementation during gestational day 6-10 suppressed the prevalence of valproic acid-induced neural tube defects, which are common malformations in offspring prenatally exposed to valproic acid, but not that of spinal nerve defects. Thus, the spinal nerve defects due to prenatal valproic acid exposure might be induced by mechanisms different from those of neural tube defects. Because spinal nerve defects were predicted to be caused by the disrupted segmental arrangement of the somites and/or that of neural crest cells, which was the origin of the dorsal root ganglia and/or abnormal polarity of the somite, this mouse model with spinal nerve defects at high incidence would be useful to examine the effects of valproic acid on the somitogenesis and morphogenesis of somite-associated structures.
Khuumii (throat or overtone singing) is a unique form of art derived from the nomadic population of Central Asia, which is a type of singing in which the singer manipulates the resonances (or formants) created as air travels from the lungs, past the vocal folds, and out of the lips to produce a melody. A total of 60 participants, aged 18-60 years (54 men and 6 women), were selected by non-random sampling method using cross-sectional study. X-ray, endoscopy, and sound research method were used in the study, and the composition of blood gas was analysed. X-ray examination determined the state during each different types of Khuumii; Shakhaa and Kharkhiraa. As the basic timbre of Shakhaa Khuumii went up progressively the larynx grew and the compression strength increased, while the basic timbre went down, and the larynx became lower. In the case of Kharkhiraa Khuumii, the larynx position was elevated to a relatively small extent compared to Shakhaa Khuumii and the distance between the sublingual bone and the larynx was large. The sublingual bone trunk lowered during Shakhaa Khuumii, while it was slightly elevated during Kharkhiraa Khuumii. The laryngeal endoscopy evaluated the movement of true and false vocal chords, glottal volume, movements of epiglottis and arytenoid cartilage, and mucosa. Furthermore, the sound frequency is 2-4 times higher than that of normal speech, and sound volume is 0.5-1 times higher. The blood gas composition test showed partial pressure (pO2), and saturation of oxygen (SaO2) decreased after performing Khuumii. In the case of Shakhaa and Kharkhiraa Khuumi, it is appropriate to divide Khuumii into two main types according to structural and functional changes in the organs involved.
Objectives: Vitamins play critical roles in cellular metabolism, growth, and many enzymatic processes of the human body. They are also crucial in signal transduction and transcription pathways of many processes, including osteoclast differentiation. This review focused on the positive or negative effect of vitamins on osteoclast differentiation in vivo and in vitro, especially signal transduction. Methods: A systematic review of the literature regarding the contributions of the osteoclast differentiation and vitamins was performed, and the most relevant findings on the effect of vitamins on osteoclast differentiation were selected. Results: Vitamin D, E, B1, B5, B6, and B12 have mainly anti-osteoporotic effects; however, their mechanism on osteoclast differentiation and activation are variable. Vitamins A and C have been considered to activate osteoclast differentiation and function, but some report a suppressive effect on osteoclast function. Vitamin K and B2 exert an inhibitory effect on osteoclast differentiation and activation both in vitro and in vivo. In contrast, a direct action of niacin, biotin, and folic acid on osteoclast differentiation and activation remains unclear. Conclusions: Collectively, vitamins act on osteoclast differentiation and function in various ways depending on cell type, cell maturation and microenvironment.
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