Elongation of the developing spinal cord is driven by Oct4-type transcription factor-mediated regulation of retinoic acid signaling in zebrafish embryos.

BACKGROUND: Elongation of the spinal cord is dependent on neural development from neuromesodermal progenitors in the tail bud. We previously showed the involvement of the Oct4-type gene, pou5f3, in this process in zebrafish mainly by dominant-interference gene induction, but, to compensate for the limitation of this transgene approach, mutant analysis was indispensable. pou5f3 involvement in the signaling pathways was another unsolved question. RESULTS: We examined the phenotypes of pou5f3 mutants and the effects of Pou5f3 activation by the tamoxifen-ERT2 system in the posterior neural tube, together confirming the involvement of pou5f3. The reporter assays using P19 cells implicated tail bud-related transcription factors in pou5f3 expression. Regulation of tail bud development by retinoic acid (RA) signaling was confirmed by treatment of embryos with RA and the synthesis inhibitor, and in vitro reporter assays further showed that RA signaling regulated pou5f3 expression. Importantly, the expression of the RA degradation enzyme gene, cyp26a1, was down-regulated in embryos with disrupted pou5f3 activity. CONCLUSIONS: The involvement of pou5f3 in spinal cord extension was supported by using mutants and the gain-of-function approach. Our findings further suggest that pou5f3 regulates the RA level, contributing to neurogenesis in the posterior neural tube.

Influence of acotiamide on 13C-urea breath test for Helicobacter pylori diagnosis.

The Helicobacter pylori infection and functional dyspepsia are often coexisted. The effect of acotiamide, a drug for functional dyspepsia, on the result of Helicobacter pylori diagnosis has yet to be studied. We evaluated the influence of acotiamide on the results of Helicobacter pylori diagnosis in the 13C-urea breath test. Twenty patients with Helicobacter pylori-positive functional dyspepsia were treated with 100 mg of acotiamide three times a day for two weeks. Changes in 13C-urea breath test were investigated before and after administration, and two weeks after administration as the follow-up period. The 13C-urea breath test and the medical questionnaire of modified frequency scale for the symptoms of gastroesophageal reflux disease were conducted at every period. Nineteen patients were included for analysis. No patients showed negative in 13C-urea breath test at Weeks 2 and 4. On the symptom scale, dyspepsia and total scores decreased from Week 0 to Week 2 and increased from Week 2 to Week 4, and the improvement rates of the dyspepsia score at Week 2 was 63%. In conclusion, we confirmed that acotiamide is unlikely to influence the result of 13C-urea breath test and it may improve the symptoms of functional dyspepsia during Helicobacter pylori eradication treatment.

A multilayered sheet-type device capable of sustained drug release and deployment control.

Minimally invasive delivery of a sustained drug release device to the body is a promising approach for treating chronic conditions such as retinal diseases. Herein, we describe a sheet-type device capable of sustained drug release and deployment control after being applied to the body through a small opened hole via a syringe-type injector. Such device consists of a four-layered structure of thin photopolymerized sheets, which are in turn made of different ratios of a mixture of polyethylene glycol dimethacrylate (PEGDM) and triethylene glycol dimethacrylate (TEGDM). A layer containing a model drug, i.e., fluorescein, was sandwiched between a controlled release and guard layer to achieve sustained unidirectional drug release. A deployment layer was then attached onto the guard layer to control the curvature of the device following deployment. The sheet-type device was sufficiently flexible to be rolled up and could be inserted into a syringe-type injector. When the device was injected into the subconjunctival space of a rabbit eye through a small opened hole, it unfolded to fit the eyeball curvature. Moreover, homogenates of the choroid/retinal pigment epithelium (RPE) as well as the retina exhibited fluorescence during 4 weeks after implantation, confirming that the drug could be delivered to the retina by using the device. This developed sheet-type device offers the possibility of achieving minimally invasive transplantation into diseased tissues and organs, and could provide improved therapeutic modalities as well as reduce possible side effects.

[Dihydropyrimidine dehydrogenase deficiency causes severe adverse effects of capecitabine].

We report the case of a 61-year-old man who experienced severe adverse effects of capecitabine because of dihydropyrimidine dehydrogenase (DPD) deficiency. In 2016, he visited our hospital for adenocarcinoma of the gastroesophageal junction and was prescribed neoadjuvant chemotherapy with capecitabine, cisplatin, and trastuzumab. On day 14 of chemotherapy, he developed severe diarrhea, canker sores, enterocolitis, febrile neutropenia, and thrombocytopenia. He was then urgently hospitalized, and anticancer treatment was stopped. We administered antibiotics and G-CSF, and he gradually recovered. However, he complained of severe bloody stools due to hemorrhagic enteritis;hence, we performed a bowel resection. The level of DPD protein, which metabolizes 5-fluorouracil (FU), was very low (2.83U/mg). Therefore, he was diagnosed with DPD deficiency, based on DPD protein or urinary pyrimidine levels, which caused serious adverse effects of capecitabine. It is a rare condition, and 5-FU administration should be avoided in DPD deficiency cases.

High Prevalence of Pantoea spp. in Microbiota Associated with the Sorghum Plant Bug Stenotus rubrovittatus (Heteroptera: Miridae).

The sorghum plant bug, Stenotus rubrovittatus (order Heteroptera: family Miridae), is a notorious insect pest in Japan that causes pecky rice. In the present study, we sampled this insect pest in the northern part of Honshu Island in Japan and investigated its associated microbiota. The results obtained showed that Pantoea dominated the associated microbiota and was the sole genus detected in all samples. The dominant Pantoea were phylogenetically close to rice pathogens. The present results suggest that the sorghum plant bug needs to be regarded and controlled not only as a notorious insect pest, but also as a potential vector of rice pathogenic Pantoea spp.

An Autopsy Case of Acute Pancreatitis Caused by Cholesterol Crystal Embolization.

Cholesterol crystal embolization (CCE) shows a poor prognosis and it can cause ischemic organ damage due to a cholesterol embolism from atherosclerotic lesions in large blood vessels. Such an embolism mainly affects the kidneys and skin, although cases involving digestive organs have also been reported. We encountered an autopsy case of CCE with damage mainly to the digestive organs, including the pancreas. The patient had non-specific abdominal symptoms or image findings. Symptomatic therapy failed to save him. CCE can involve the digestive organs, and so must be differentiated from abdominal pathologies. Moreover, conventional treatments may be ineffective, and new treatments might thus be necessary.