A new method with an explant culture of the utricle for assessing the influence of exposure to low-frequency noise on the vestibule

ABSTRACT

Health risks attributed to low-frequency noise (LFN) exposure are a serious global issue. Therefore, the development of a method for a prevention based upon risk assessments for LFN is important. Previously in vivo exposure of mice to LFN at 100 Hz, 95 dB for 1 hr produced imbalance with breakage of the otoconial membrane, which covers hair cells as well as impaired activity of hair cells in the vestibule. However, methods for inhibition of LFN-mediated imbalance have not been developed. At present, there are no apparent techniques available with in vitro or ex vivo assessments to evaluate LFN-mediated imbalance by direct administration of preventive chemicals into the vestibule. Our findings demonstrated the usefulness of an explant culture of the utricle with a fluorescent styryl dye, FM1-43FX. In addition, examination of the morphology of the otoconial membrane with explant cultures of utricles was conducted to determine the risk of LFN. Ex vivo exposure of the utricle to LFN at 100 Hz, 95 dB for 1 hr induced breaks in the otoconial membrane as well as decreased uptake of FM1-43FX in hair cells. Taken together, the results of this study provide a novel technique for assessing the risk of LFN exposure using an ex vivo experiment.     

Lactate Levels in Bowel Strangulation With Experimental Animal Model

Bowel strangulation is a common disease and often requires an urgent operation. Our previous report showed that lactate concentration in the blood is a good predictive marker for emergency. However, the alteration in lactate levels during the course of bowel strangulation remains unclear. We have investigated the progressive increase of lactate after induction of bowel strangulation with animal experiments. Thirty-six mice were randomly divided into 6 groups: 0, 8, 16, 24, 48, and 72 hours after operation. Under anesthesia, laparotomy was performed and a 5-cm segment of terminal ileum with the mesenteric artery and veins was ligated to create a strangulation obstruction. After operation, the arterial blood was collected and lactate concentration and pH were measured using a blood gas analyzer. Lactate concentration in the 8-hour group was markedly increased, while pH decreased significantly (P < 0.05). Lactate concentrations were kept at a high level from 8 to 72 hours after operation. The time lag between strangulation and an increase of lactate is 8 hours. Our study is the first report of a bowel strangulation mouse model. Therefore, it would be possible to find a more specific marker of bowel strangulation using our experimental model.Key words: Bowel strangulation, Lactate, Blood gas analyzer, Animal modelBowel strangulation is a common but very serious condition. Although some patients of it can be cured with a safe nonoperative management, others require an emergent operation. Therefore, an accurate and prompt diagnosis is important to consider an effective therapeutic strategy. Several studies have proposed predictive factors including acidosis and serum concentrations of creatine phoshokinase, lactic dehydrogenase, and amylase.^1–3 Nonetheless, the early detection of bowel strangulation is often difficult, and reliable diagnostic information that may suggest its presence is required in clinical practice.Lactate is a product of anaerobic metabolism of glucose, and its concentration in the arterial blood is a good indicator of the severity of metabolic acidosis secondary to tissue hypoperfusion. The time needed to normalize the serum lactate levels is an important prognostic factor for survival.^4–7 In ischemia associated with bowel strangulation, anaerobic metabolism causes an increase in the concentrations of lactate. We previously reported that lactate concentration is a good predictive factor for strangulation obstruction.⁸However, the alterations of lactate concentration during the course of bowel strangulation remain unclear. In order to reveal various pathophysiological changes, including the alterations of lactate concentration after bowel strangulation, it is very profitable to develop a novel animal model, especially with a genetically controlled mouse. In the present study, the arterial blood was obtained from mice at designated times after they had undergone a procedure to cause the closed loop obstruction, and pH and lactate concentrations in it were measured by using a blood gas analyzer. We focused on the progressive increase of lactate during first 72 hours after induction of bowel strangulation.     

Squamous Cell Carcinoma after Endoscopic Injection Sclerotherapy for Esophageal Varices

We report two cases of squamous cell carcinoma of the esophagus following endoscopic injection sclerotherapy for esophageal varices. The interval between sclerotherapy and the development of carcinoma was 24 months in case 1 and 21 months in case 2. The sclerosant was 5% sodium morrhuate in case 1 (total dose, 10 ml) and 5% ethanolamine oleate in case 2 (45.5 ml). Although no recurrent variceal bleeding occurred after sclerotherapy, we could not perform any curative surgical treatment for esophageal cancer because of the advanced stage of the cancer and the severity of the accompanying liver dysfunction. It is difficult to determine the relationship between sclerotherapy and carcinoma; however, long-term surveillance is essential to avoid overlooking a neoplasm in the esophagus after endoscopic injection sclerotherapy.     

Effect of synthetic porcine neuropeptide Y (NPY) on splanchnic blood flows and Exocrine pancreatic secretion in dogs

This study examined the effect of synthetic porcine neuropeptide Y on the splanchnic blood flows and the exocrine pancreatic secretion in dogs. Graded doses of neuropeptide Y (0.1–5 g/kg, intravenous) caused dose-dependent reduction of the secretin-stimulated exocrine pancreatic secretion and of the blood flows in the superior mesenteric artery, the portal vein, and the pancreatic tissue. Neuropeptide Y at 5 g/kg reduced the blood flows to 45.9±13.3% (superior mesenteric artery), 63.0±10.5% (portal vein), and 77.9±4.8% (pancreatic tissue), respectively. This dose also reduced secretin-stimulated pancreatic juice volume and CCK-8 plus secretin-stimulated protein output to 65.2±9.3 and 63.3±14.0%, respectively. This study shows a potent vasoconstrictor effect of neuropeptide Y on splanchnic vessels. Neuropeptide Y also inhibited exocrine pancreatic secretion in a significant correlation with the reduction in pancreatic tissue blood flow, which suggests that reduction in the blood flow may be one of the possible mechanisms of the inhibitory action of neuropeptide Y on exocrine secretion.This work was supported by a grant from the Ministry of Education, Japan (A-61440060).     

早期胃癌和进展期胃癌患者幽门螺杆菌感染与胃黏膜组织学特点的关系

背景幽门螺杆菌(H.pylori)感染已被确认为慢性胃炎的主要病因,由慢性非萎缩性胃炎、慢性萎缩性胃炎至肠化生,经过数十年最终可能导致胃癌发生。目的评价H.pylori感染与胃镜检查正常者、慢性胃炎、早期胃癌和进展期胃癌患者胃黏膜组织学特点的关系。方法在受检者胃窦大弯侧、胃体大弯侧和胃角处各取一块黏膜活检标本,以Giemsa染色和免疫组化染色检测H.pylori感染情况;以HE染色评价胃黏膜炎症、活动性、萎缩和肠化生情况。结果慢性胃炎、早期胃癌和进展期胃癌患者的总体H.pylori感染率均显著高于胃镜检查正常者(52.4%、52.4%和81.2%对44.9%,P<0.05),慢性胃炎与早期胃癌患者的感染率无显著差异,但均显著低于进展期胃癌患者(P<0.05)。胃镜检查正常和慢性胃炎组H.pylori感染者的胃黏膜炎症、活动性、萎缩和肠化生检出率均显著高于无感染者(P<0.05);早期胃癌和进展期胃癌组H.pylori感染者的炎症活动性检出率显著高于无感染者(P<0.05),而炎症、萎缩和肠化生检出率与无感染者无显著差异。结论由H.pylori感染引起的胃黏膜慢性炎症、萎缩和肠化生可能在胃癌的发生、发展过程中起直接或间接作用。     

Acute myeloid leukaemia with myelodysplastic features in children: a report of Japanese Paediatric Leukaemia/Lymphoma Study Group

The clinical characteristics and prognostic relevance of acute myeloid leukaemia (AML) with myelodysplastic features remains to be clarified in children. We prospectively examined 443 newly diagnosed patients in a multicentre clinical trial for paediatric de novo AML, and found ‘AML with myelodysplasia‐related changes’ (AML‐MRC) according to the 2008 World Health Organization classification in 93 (21·0%), in whom 59 were diagnosed from myelodysplasia‐related cytogenetics alone, 28 from multilineage dysplasia alone and six from a combination of both. Compared with 111 patients with ‘AML, not otherwise specified’ (AML‐NOS), patients with ‘AML‐MRC’ presented at a younger age, with a lower white blood cell count, higher incidence of 20–30% bone marrow blasts, unfavourable cytogenetics and a lower frequency of Fms‐like tyrosine kinase 3 internal tandem duplication (FLT3‐ITD), NPM1 and CEBPA mutations. Complete remission rate and 3‐year probability of event‐free survival were significantly worse in ‘AML‐MRC’ patients (67·7 vs. 85·6%, P < 0·01, 37·1% vs. 53·8%, P = 0·02, respectively), but 3‐year overall survival and relapse‐free survival were comparable with ‘AML‐NOS’ patients. By multivariate analysis, FLT3‐ITD was solely associated with worse overall survival. These results support the distinctive features of the category ‘AML‐MRC’ even in children.