Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (OECD): Familiarization Using Cyclophosphamide

Combined Repeat Dose and Reproductive/Developmental ToxicityScreening Test (OECD): Familiarization Using Cyclophosphamide.TANAKA, S., KAWASHIMA, K., NAITO, K., USAMI, M., NAKADATE, M.,IMAIDA, K., TAKAHASHI, M., HAYASHI, Y., KUROKAWA, Y., AND TOBE,M. (1992A, Y., AND TOBE, M. (1992). Fundam. Appl. Toxicol. 18,89–95. A familiarization study was conducted on the "Combined RepeatDose and Reproductive/Developmental Toxicity Screening Test(ReproTox)" proposed by the OECD. Cyclophosphamide (CP) at dosesof 6.7, 4.5, 3, 2, and 0 mg/kg body wt was given daily by gavageto groups of 12 male and 12 female Sprague-Dawley rats. As aresult, anemia and leukopenia were evident in treated males.The absolute and relative thymus and spleen weights were decreasedin treated rats. Histopathologically, atrophy of the thymus,spleen, and bone marrow was observed. With respect to the reproductive/developmentaltoxicity, dose-dependent increases in postimplantation lossof fetuses and postnatal death were found in dams given CP.The body weight of pups treated with CP was significantly loweredin a dose-related manner. Thus the results demonstrated mostof the known toxicological properties of CP, except the adverseeffects on spermatogenesis and fertility. Therefore ReproToxcan be considered as a useful screening test for assessing repeatdose and reproductive/developmental toxicity of existing chemicalsof high production volume.     

Research on Fall Prevention and Protection from Heights in Japan

The high frequency of fall accidents is a serious problem in Japan. Thus, more stringent countermeasures for preventing falls from scaffolds were developed and incorporated into institutional guidelines. These countermeasures aim to decrease deaths caused by falls from scaffolds. Despite the improvements in such measures, however, the rate of accidental fall deaths remains high in Japan’s construction industries. To improve the rigor of the countermeasures, a committee was established in our institute by the Japan Ministry of Health, Labour, and Welfare. This committee investigated the regulations applied in other countries and evaluated construction industry compliance with existing fall prevention guidelines. After considerable research and discussion, the Occupational Safety and Health Regulations and Guidelines were amended in 2009. The effects of the amended regulations have recently been investigated on the basis of accident reports. This paper describes the investigation and its results. The paper also discusses other research and workplace safety countermeasures for preventing falls and ensuring fall protection from heights.     

Influence of Body Position on Defecation in Humans

Objectives: To compare three positions for defecation by measuring abdominal pressure and the anorectal angle simultaneously. Methods: We recruited six healthy volunteers. The videomanometric measures included simultaneous fluoroscopic images, abdominal pressures, subtracted rectal pressures and anal sphincter pressures. Three positions were used: sitting, sitting with the hip flexing at 60 ° with respect to the rest of the body, and squatting with the hip flexing at 22.5 ° with respect to the rest of the body. Results: Basal abdominal pressure before defecation on hip‐flex sitting was lower than that with normal sitting, although the difference did not reach statistical significance. Basal abdominal pressure before defecation on squatting (26 cmH₂O) was lower than that with normal sitting (P < 0.01). Abdominal pressure increase (strain) on hip‐flex sitting was lower than that with normal sitting, although this difference did not reach statistical significance. Similarly, the abdominal pressure increase on squatting was smaller than that with normal sitting, and yet the difference did not reach statistical significance. The rectoanal angle on defecation on hip‐flex sitting did not differ from that with normal sitting. The rectoanal angle on defecation on squatting (126 °) was larger than that with normal sitting (100 °) (P < 0.05), and was also larger than that with hip‐flex sitting (99 °) (P < 0.01). Conclusion: The results of the present study suggest that the greater the hip flexion achieved by squatting, the straighter the rectoanal canal will be, and accordingly, less strain will be required for defecation.     

Keratinocyte growth factor is an endogenous stimulant of rabbit gastric epithelial cell proliferation and migration in primary culture

Mesenchymal-epithelial interactions are important in the gastric mucosal repair. However, specific factors responsible for such interactions have not been established. In the present study, keratinocyte growth factor (KGF) significantly stimulated proliferation of gastric epithelial cells dose dependently and synergistically with hepatocyte growth factor (HGF), epidermal growth factor (EGF) and insulin. Restitution of gastric epithelial monolayers was also assessed, using a round wound restitution model. Keratinocyte growth factor facilitated the restitution of gastric epithelial cells significantly but did not have any effects on gastric fibroblasts. Keratinocyte growth factor receptor mRNA was expressed by gastric epithelial cells, indicating that these effects were elicited by the specific receptor mediated pathway. Northern blot analysis revealed the expression of KGF mRNA in gastric fibroblasts but not in gastric epithelial cells, indicating the production of KGF. These results suggest that KGF might be involved in gastric mucosal repair, through mesenchymal-epithelial interaction.     

Pulmonary surfactant transport in alveolar type II cells

Abstract:   Pulmonary surfactant (PS) is a mixture of several lipids (mainly phosphatidylcholine; PC) and four apoproteins (A, B, C and D). The classical hypothesis of PS transport suggests that PS is synthesized in the endoplasmic reticulum and transported to the lamellar body (LB) via the Golgi apparatus. However, recent studies have raised questions regarding this single route. This study examined, independently, the intracellular trafficking route of three different components of PS, that is, PC, SP-A and SP-B. Alveolar type II cells were isolated from Sprague–Dawley rats or Japanese white rabbits. The cells were cultured with either [³H]choline or [³⁵S]methionine/cysteine with or without brefeldin A, which disassembles the Golgi apparatus. LB was purified from disintegrated cells with sucrose density gradient centrifugation. [³H]PC was extracted from radiolabeled media, cells, and the LB fraction with Bligh–Dyer's method. [³⁵S]SP-A or [³⁵S]SP-B was immunoprecipitated from each sample with a specific antibody. [³H]PC was transported and stored to the LB via a Golgi-independent pathway. [³⁵S]SP-A was transported to the Golgi apparatus, underwent glycosylation, and was then constitutively secreted. The secreted [³⁵S]SP-A was re-uptaken into the LB. [³⁵S]SP-B was transported and stored to the LB via the Golgi-dependent pathway. These results indicate that, rather than a single route, surfactant components take different pathways to reside in the LB. These different pathways may reflect the different nature and role of each surfactant component such as surface tension-lowering activity and innate host defense.