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Acrylamide (AA) is a neurotoxicant that causes synaptic impairment in distal axons. We previously found that developmental exposure to AA decreased proliferation of late-stage neural progenitor cells (NPCs) in the hippocampal neurogenesis of the dentate gyrus (DG) in rats. To investigate whether hippocampal neurogenesis is similarly affected by AA exposure in a general toxicity study, AA was administered to 7-week-old male rats via oral gavage at dosages of 0, 5, 10, and 20 mg/kg for 28 days. In the subgranular zone (SGZ) and granule cell layer, AA decreased the densities of doublecortin-positive

An anesthetic mixture of medetomidine, midazolam and butorphanol (MMB) has been recently used in laboratory animals. We observed corneal opacity in nephrectomized rats that had undergone two operations under MMB anesthesia at 4 and 5 weeks of age. To evaluate the features of this corneal opacity, ophthalmic examinations were conducted in 83 nephrectomized rats, and 8 representative animals with corneal opacity were evaluated histopathologically 4 weeks after operation. The ophthalmic examinations revealed that 66/83 animals had corneal opacity, which was characterized histopathologically by mineralization with or without inflammation in the corneal stroma. In addition, to examine the possible causes of this corneal opacity, we investigated whether similar corneal changes were induced by the MMB anesthetic treatment in normal rats. The MMB anesthetic was administered twice to 4- and 5-week-old normal SD rats (5 animals/age) in the same manner as for the nephrectomized rats. Ophthalmic examinations were conducted in all the animals once a week, and the animals were necropsied 4 weeks after the first administration. In normal rats, similar corneal opacity was observed after the first administration, and increases in the severity and size of the corneal opacity were noted after the second administration. In conclusion, this study revealed the features of corneal opacity in rats undergoing nephrectomy under MMB anesthesia and the occurrence of similar corneal opacity in normal rats treated with MMB anesthetic. To the best of our knowledge, this is the first report of corneal opacity related to MMB anesthetic treatment in rats.

TP0446131, developed as an antidepressant agent, was found to cause lenticular opacity in a 13-week repeated-dose study in dogs. Histopathologically, the lenticular opacity was observed as a degeneration of the lens fibers, characterized by irregularity in the ordered arrangement of the fibers which is necessary to maintain the transparency of the lens, and was considered to manifest clinically as cataract. To evaluate the development mechanism of the lenticular opacity, the chemical constituents of the lens, which is known to be associated with the development of cataract, were examined. The results of liquid chromatography-tandem mass spectrometry analysis revealed an increase in the amplitudes of 3 unknown peaks in a dose- and time-dependent manner in the lens, with no remarkable changes in the other chemical components tested. In addition, the content of cholesterol, alterations of which have been reported to be associated with cataract, remained unchanged. The mass spectral data and chromatographic behavior of the 3 peaks indicated that these peaks corresponded to sterol-related substances, and that one of them was 7-dehydrocholesterol, a precursor of cholesterol biosynthesis. This finding suggested that TP0446131 exerts some effects on the cholesterol biosynthesis pathway, which could be involved in the development of the cataracts. Furthermore, increases in the levels of these sterol-related substances were also detected in the serum, and were, in fact, noted prior to the onset of the cataract, suggesting the possibility that these substances in the serum could be used as potential safety biomarkers for predicting the onset of cataract induced by TP0446131.

We collected historical control data derived from pretreatment ophthalmologic examinations of young (4 to 7 wk of age) Sprague–Dawley (Crl:CD[SD]) male, (2033, 42 lots) and female (1322, 32 lots) rats used in toxicity studies at our facility from 2004 through 2015. Ophthalmologic examination of male and female rats by using a binocular indirect ophthalmoscope and slit lamp revealed high incidences of corneal opacity (61% and 60%, respectively), lenticular opacity (43% and 47%), persistent hyaloid artery (21% and 17%), and retinal folds (27% and 27%). All other ocular abnormalities of the globe, conjunctiva, cornea, anterior chamber, lens, iris, vitreous, and choroid or retina occurred at incidences of less than 5%. Corneal opacities were localized mainly in the corneal nasal (38% and 37%) and paracentral (32% and 33%) areas, and lenticular opacities predominantly occurred in the nuclear area (31% and 34%). We then compared the incidences of spontaneous ocular abnormalities between the first (2004 through 2009) and second (2010 through 2015) 6-y periods. Corneal opacity and persistent hyaloid artery in male and female rats occurred more frequently during the second 6-y than during the first (corneal opacity, second period: male, 68%; female, 66%; corneal opacity, first period: 49% and 51%; persistent artery, second period, 26% and 23%; persistent artery, first period; 12% and 10%). These results support the importance of updating historical control data regularly and providing useful information for toxicologists and ophthalmologists to differentiate treatment-related changes from spontaneous lesions.

The rasH2 transgenic (Tg) mice are susceptible to genotoxic and some non-genotoxic carcinogens. In carcinogenicity studies carried out using rasH2 Tg mice, the carcinogenic potential of chemicals are evaluated over a 26-week experimental period. In the present study, we examined the comprehensive gene expressions in the lungs of Tg and non-Tg mice prior to the induction of malignant tumors. Urethane (UR), a mutagenic carcinogen, was administered for 4 weeks, and thereafter withdrawn for 22 weeks. N-methylolacrylamide (NMA), a non-mutagenic carcinogen, was administered for 26 weeks. At week 4, gene expression analysis of non-neoplastic part of the lungs demonstrated changes in the expressions of the cell-cycle and inflammation related genes following UR and NMA treatment, respectively, in both the Tg and non-Tg mice. The gene expressions of epireguline, aurora kinase B, and cyclin B1 increased in the UR-treated Tg mice. We also found an increase in the plasma carcinoembryonic antigen level in the UR-treated Tg mice. Although UR treatment induced the formation of adenomas or adenocarcinomas in the lungs in all mice, earlier induction was apparent in the Tg mice. NMA treatment was found to induce the formation of adenomas and adenocarcinomas at week 26 in the Tg mice, but not in the non-Tg mice, and no expressions of specific genes were apparent in either genotype of mice. Our results indicate that analysis of cancer-related gene expressions in the lungs and plasma biomarkers at week 4 in rasH2 Tg mice could be a screening tool for carcinogenicity, especially of mutagenic carcinogens.

The river mouth closure of the Okukubi River in Okinawa Prefecture, flowing into the coral reef, was studied. In this area, the shoreline material was extensively excavated after World War II, resulting in the disappearance of sand beach. Since then, coral sand was naturally supplied from the reef edge, resulting in recovering sandy beach. Sand reached the shoreline was then transported by longshore sand transport due to waves, and the river mouth bar was formed. The river mouth closure associated with this sand accumulation was predicted by the BG model proposed by Serizawa et al. (2006). The predicted beach changes are in good agreement with the measured.

バクテリアフィルターが簡易持続注入装置の注入速度に及ぼす影響について検討した.婦人科手術症例40例を,フィルター装着群(F群)と非装着群(C群)各20例ずつに分け,各群での平均注入速度を比較した.F群の平均注入速度(±SD)は0.43±0.10ml•hr-1で,C群の0.52±0.11ml•hr-1に比較して有意に低下していた.バクテリアフィルターは,硬膜外留置期間中の感染予防対策の一つであるが,バルーンインフューザーとの併用時には回路抵抗増大によって流量を低下させることが示された.

要旨 術中回収式自己血輸血を用いて,腹部大動脈瘤人工血管置換術を行った45例について検討した.自己血輸血量は,平均2,282mlで総輸血量の79%を占め,45例中18例(40%)は自己血輸血のみで手術を終了することができた.自己血輸血のみを行った18例では,術後において,血中ヘモグロビン濃度・血小板数の低下,血中総ビリルビン値の上昇,肺胞-動脈血酸素分圧較差の拡大が認められた.また,血漿β-thromboglobulinの有意の上昇が認められ,血小板の活性化が示唆された.しかし,術後の凝固異常,感染症,重篤な腎機能障害は認められなかった.回収式自己血輸血は,他家血輸血の必要量を減少することができ,有用な方法であると考えられる.

We have investigated the effects of anesthetic and related agents on Ca2+-induced Ca2+ release (CICR) in heavy sarcoplasmic reticulum isolated from rabbit skeletal muscle. The purpose of this study is to elucidate their possible role as triggering agents in malignant hyperthermia (MH). None of the agents (ketamine, procaine, lidocaine, succinylcholine, pancuronium and fentanyl) affected CICR at clinical concentrations. At higher concentrations, procaine, pancuronium and succinylcholine inhibited CICR, but ketamine rather potentiated it. It is unlikely that lidocaine is a potent facilitator of CICR at any concentrations. We conclude that procaine, lidocaine, non-depolarizing muscle relaxants and opiate can be used safely for MH susceptible patients and that ketamine and succinylcholine are not recommended.