A patient with repeated syncopal attacks after using isosorbide dinitrate

The case of a patient with repeated attacks of collapse induced by sublingual isosorbide dinitrate is reported. The patient was an 81 year-old female who was admitted to Yura Hospital because of attacks of precordial pain. Several minutes after the sublingual administration of isosorbide dinitrate (10 mg) for an anginal attack, she developed a sensation of general weakness, and thereafter because unconscious. Arterial blood pressure fell and became unmeasurable. Electrocardiograms recorded during the syncopal attack showed sinus tachycardia and significant elevation of ST-segment in right precordial leads. In response to a drip infusion of noradrenaline, arterial blood pressure returned to normal with recovery of consciousness. Two similar syncopal attacks induced by sublingual isosorbide dinitrate occurred in the next three days. These attacks were not due to augmentation of the vagal reflex. Decrease of venous return probably was the primary etiological factor.</p

Effects of Interval Time of the Epley Manoeuvre

Objective: The Epley maneuver (EM) has an immediate effect: rapid reduction of positional nystagmus. Benign paroxysmal positional vertigo (BPPV) causes BPPV fatigue, which constitutes fatigability of positional nystagmus and vertigo with repeated performance of the Dix-Hallpike test; notably, BPPV fatigability becomes ineffective over time. We hypothesized that the immediate effect of the EM is caused by BPPV fatigue. Therefore, we suspected that performance of the EM with intervals between head positions would worsen the immediate reduction of positional nystagmus in patients with BPPV, because BPPV fatigability would become ineffective during performance of this therapy. Methods: Forty patients with newly diagnosed BPPV were randomly assigned to the following two groups; one group performed the EM without intervals between positions (group A), and the other group performed the EM with 3 min intervals between positions (group B). The primary outcome measure was the ratio of maximum slow-phase eye velocity (MSPEV) of positional nystagmus soon after the EM, compared with that measured before the EM. Secondary outcome included whether a 30 min interval after the EM enabled recovery of MSPEV of positional nystagmus to the original value. This study followed the CONSORT 2010 reporting standards. Results: In both groups A and B, the immediate effect of the EM could be observed, because MSPEV during the second Dix-Hallpike test was significantly smaller than MSPEV during the first Dix-Hallpike test (p < 0.0001 in group A, p < 0.0001 in group B). The primary outcome measure was larger in group B than in group A (p = 0.0029). The immediate effect faded 30 min later (secondary outcome). Conclusions: This study showed that the EM had an immediate effect both with and without interval time in each head position of the EM. Because setting interval time in each head position of the EM reduced the immediate effect of the EM, interval time during the EM adds less benefit. This finding can reduce the effort exerted by doctors, as well as the discomfort experienced by patients with pc-BPPV, during EM. However, this immediate effect may be caused by BPPV fatigue, and may fade rapidly

Effects of Combined Low Glutathione with Mild Oxidative and Low Phosphorus Stress on the Metabolism of Arabidopsis thaliana

Plants possess highly sensitive mechanisms that monitor environmental stress levels for a dose-dependent fine-tuning of their growth and development. Differences in plant responses to severe and mild abiotic stresses have been recognized. Although many studies have revealed that glutathione can contribute to plant tolerance to various environmental stresses, little is known about the relationship between glutathione and mild abiotic stress, especially the effect of stress-induced altered glutathione levels on the metabolism. Here, we applied a systems biology approach to identify key pathways involved in the gene-to-metabolite networks perturbed by low glutathione content under mild abiotic stress in Arabidopsis thaliana. We used glutathione synthesis mutants (cad2-1 and pad2-1) and plants overexpressing the gene encoding γ-glutamylcysteine synthetase, the first enzyme of the glutathione biosynthetic pathway. The plants were exposed to two mild stress conditions—oxidative stress elicited by methyl viologen and stress induced by the limited availability of phosphate. We observed that the mutants and transgenic plants showed similar shoot growth as that of the wild-type plants under mild abiotic stress. We then selected the synthesis mutants and performed multi-platform metabolomics and microarray experiments to evaluate the possible effects on the overall metabolome and the transcriptome. As a common oxidative stress response, several flavonoids that we assessed showed overaccumulation, whereas the mild phosphate stress resulted in increased levels of specific kaempferol- and quercetin-glycosides. Remarkably, in addition to a significant increased level of sugar, osmolytes, and lipids as mild oxidative stress-responsive metabolites, short-chain aliphatic glucosinolates over-accumulated in the mutants, whereas the level of long-chain aliphatic glucosinolates and specific lipids decreased. Coordinated gene expressions related to glucosinolate and flavonoid biosynthesis also supported the metabolite responses in the pad2-1 mutant. Our results suggest that glutathione synthesis mutants accelerate transcriptional regulatory networks to control the biosynthetic pathways involved in glutathione-independent scavenging metabolites, and that they might reconfigure the metabolic networks in primary and secondary metabolism, including lipids, glucosinolates, and flavonoids. This work provides a basis for the elucidation of the molecular mechanisms involved in the metabolic and transcriptional regulatory networks in response to combined low glutathione content with mild oxidative and nutrient stress in A. thaliana

Gene Expression and Protein Synthesis in Mitochondria Enhance the Duration of High-Speed Linear Motility in Boar Sperm

Sperm motility patterns are continuously changed after ejaculation to fertilization in the female tract. Hyperactivated motility is induced with high glucose medium in vitro or the oviduct fluids in vivo, whereas sperm maintain linear motility in the seminal plasma or the uterine fluids containing low glucose. Therefore, it is estimated that sperm motility patterns are dependent on the energy sources, and the mitochondrial oxidative phosphorylation is activated to produce ATP in low glucose condition. To elucidate these hypotheses, boar sperm was incubated in different energy conditions with the transcription and translation inhibitors in vitro. Sperm motility parameters, mitochondrial activity, ATP level, gene expression and protein synthesis were analyzed. Sperm progressive motility and straight-line velocity were significantly increased with decreasing glucose level in the incubation medium. Moreover, the mitochondrial protein turnover meaning transcription and translation from mitochondrial genome in sperm is activated during incubation. Incubation of sperm with mitochondrial translation inhibitor (D-chloramphenicol) suppressed mitochondrial protein synthesis, mitochondrial activity and ATP level in sperm and consequently reduced the linear motility speed, but not the motility. Thus, it is revealed that the mitochondrial central dogma is active in sperm, and the high-speed linear motility is induced in low glucose condition via activating the mitochondrial activity for ATP generation.This work was supported in part by Livestock Promotional Funds of Japan Racing Association (JRA) grant no. H30-279 and by Hiroshima Cryopreservation Service Co., grant no. H30-1 (to MS). ZZ was supported by China Scholarship Council during a visit of “Zhendong Zhu” to Hiroshima University (#CSC201706300110).The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphys.2019.00252/full#supplementary-materia

日本語接続詞の捉え方 : ソレデ，ソシテ，ソレガ，ソレヲ，ソコデについて

成城大学東洋大学Seijo UniversityToyo University本稿は，指示詞研究と接続詞研究のインターフェースを見出す試みである。先駆的な研究がわずかに認められるものの，これまで両者のインターフェースが一つの研究領域として掘り起こされることはほとんどなかった。ソレデ，ソシテ，ソレガ，ソレヲ，ソコデはいずれもソ系列指示詞を含む接続詞であるが，このような接続詞のより精密な記述のために，あるいは，それらの歴史的な変化を記述する基盤を築くために，代示要素を含む接続詞についての一つの整理のし方を示したい。まず，ソ系列指示詞を含む接続詞のソの照応のあり方に着目し，そのはたらきに少なくとも3類の区別が認められることを明らかにする。また，モーダル助動詞の意味的スコープ，疑問助詞の意味的スコープを利用して上述の接続詞について文中での統語的な位置を考える。以上の観点からの分析を総合した上で，これまでの整理のし方では取り出すことのできなかったソレデ，ソシテ，ソレガ，ソレヲ，ソコデにおける個別性と共通性を示す。The purpose of this paper is to show that there is an interface between connectives that are composed of so- and other elements and demonstrative so- in analyzing Japanese connectives: sorede, sosite, sorega, soreo, sokode. The so- that is included in these connectives has an anaphoric relation with sentence(s) or assumption(s), but the anaphoric relation of so- is not the same, as follows:(1) so- in sorede and soreo can have an anaphoric relation with several previous sentences, and the meaning of the sentences can be either stative or non-stative.(2) so- in sorega and sokode can have an anaphoric relation with several previous sentences, and the meaning of the sentences must be stative.(3) so- in sosite is limited to the anaphoric relation with the immediately preceding sentence, and the meaning of the sentence can be either stative or non-stative.Furthermore, by observing the semantic scope of modal auxiliary nodaroo and interrogative particle noka, the connectives described above are divided into three groups: sorede and sosite are inside the scope of nodaroo; sorega and soreo are outside the scope of nodaroo and inside the scope of noka; and sokode is outside the scope of noka

Lambert-Eaton Myasthenic Syndrome Caused by Nivolumab in a Patient with Squamous Cell Lung Cancer

Lambert-Eaton myasthenic syndrome (LEMS) is a representative paraneoplastic neurological syndrome. Recently, nivolumab, an anti-programmed cell death 1 inhibitor, has been approved for advanced non-small-cell lung cancer. Careful attention should be paid to immune-related adverse events (irAEs), including neurotoxicity. We herein report a 73-year-old woman with LEMS that occurred during nivolumab treatment for pulmonary squamous cell carcinoma. After the 20th week of nivolumab, she experienced various neurological symptoms such as ptosis, lower limb weakness, and photophobia. Findings from a nerve conduction study and a positive anti-P/Q-type voltage-gated calcium channel antibody made a diagnosis of LEMS. Pyridostigmine and 3,4-diaminopyridine temporarily improved her symptoms. This was the first case of LEMS as a neurological irAE. LEMS should be considered as a possible neurological irAE