Lack of hepatocarcinogenicity of 2,2’-[1,2-ethanediylbis(oxymethylene)]bis-oxirane, 3-hydroxy-2-naphthoic acid,and acetoacetanilide in a medium-term rat liver bioassay

The carcinogenicity of 2,2’-[1,2-ethanediylbis(oxymethylene)]bis-oxirane (ethylene glycol diglycidyl ether; EGDE), 3-hydroxy-2-naphthoic acid (HNA), and acetoacetanilide (AAA) was investigated using a medium-term rat liver bioassay for an occupational safety assessment. F344 male rats were administered a single intraperitoneal injection of diethylnitrosamine (200 mg/kg body weight (bw)/day) and then starting 2 weeks later, they received EGDE at 6, 20, and 60 mg/kg bw/day, HNA at 20, 60, and 200 mg/kg bw/day, or AAA at 60, 200, and 600 mg/kg bw/day by oral gavage for 6 weeks. The animals in the positive control group received phenobarbital sodium solution (PB, 25 mg/kg bw/day) by oral gavage and those in the negative control group received a vehicle (water/corn oil) during the administration period of test substances in this model. All animals were subjected to two-thirds partial hepatectomy at week 3 and euthanized at week 8. Neither the number nor the area of hepatocellular foci positive for glutathione S-transferase placental form (GST-P) increased in any of the EGDE, HNA, or AAA treated groups. However, the number and area of GST-P-positive foci significantly increased in the positive control group treated with PB. The results indicate that EGDE, HNA, and AAA lack hepatocarcinogenicity in rats.     

Genetically structured population and demographic history of the goldlined spinefoot <Emphasis Type="Italic">Siganus guttatus</Emphasis> in the northwestern Pacific

Sequence variation of the mitochondrial DNA was analyzed to examine the genetic structure and demographic history of the goldlined spinefoot Siganus guttatus in the northwestern Pacific. In total, 451 nucleotide sequences spanning from the tRNA^Thr gene to the middle of the control region were determined from 254 specimens collected from five localities; three in the Ryukyu Islands (Okinawa, Miyako, and Ishigaki Islands), Taiwan, and Cebu Island of the Philippines; 73 variable sites and 75 haplotypes were detected. Our results showed restricted gene flow and genetic differentiation among all populations, with the exception of genetic homogeneity between the Miyako and Ishigaki populations; that is, this species will be able to cross between Miyako and Ishigaki (ca. 120 km) by the transport of pelagic larvae, and gene flow between Okinawa and Miyako/Ishigaki Islands (ca. 330–450 km) is restricted. A non-dispersal strategy will lead to restricted gene flow and genetic structuring in S. guttatus. Both the neutrality tests and the mismatch distribution indicated that S. guttatus might have been in populations at demographic equilibrium. This suggests that population range expansion may have been restricted owing to a non-dispersal strategy that may have restrained S. guttatus from demographic expansion after glaciation. The result will be of fundamental importance for resource management of this species.     

In vitro antitrypanosomal activities of quassinoid compounds from the fruits of a medicinal plant, Brucea javanica

The medicinal plant Brucea javanica (L.) Merr. (Simaroubaceae) is widely distributed throughout Asia where its bitter fruits have been used in traditional medicine for various ailments. Fifteen C-20 quassinoids were isolated from the fruits of B. javanica and examined for their in vitro antitrypanosomal activities against trypomastigotes of Trypanosoma evansi. Bruceine A, bruceantinol, bruceine C, brusatol, and bruceine B showed strong antitrypanosomal activities with IC(50) values in the range of 2.9-17.8nM, which compared well with the standard trypanocidal drugs diminazene aceturate (IC(50)=8.8nM) and suramin (IC(50)=43.2nM). However, dehydrobruceine A, dehydrobruceine B, and dehydrobrusatol were about 2100, 900, and 1200 times less active, respectively, than bruceine A, bruceine B, and brusatol. The relationship of the structure and antitrypanosomal activity of these quassinoid compounds suggested that the presence of a diosphenol moiety in ring A and the nature of the C-15 side chain are important for their activities against T. evansi. This is the first report on the antitrypanosomal activity of isolated quassinoids.     

Quantitative trait loci for leg weakness traits in a Landrace purebred population

Leg weakness in pigs is a serious problem in the pig industry. We performed a whole genome quantitative trait locus (QTL) analysis to find QTLs affecting leg weakness traits in the Landrace population. Half-sib progeny ( n  = 522) with five sires were measured for leg weakness traits. Whole genome QTL mapping was performed using a half-sib regression-based method using 190 microsatellite markers. No experiment-wide significant QTLs affecting leg weakness traits were detected. However, at the 5% chromosome-wide level, QTLs affecting leg weakness traits were detected on chromosomes 1, 3, 10 and 11 with QTL effects ranging from 0.07 to 0.11 of the phenotypic variance. At the 1% chromosome-wide level, QTLs affecting rear feet score and total leg score were detected on chromosomes 2 and 3 with QTL effects of 0.11 and 0.13 of the phenotypic variance, respectively. On chromosome 3 and 10, some QTLs found in this study were located at nearby positions. The present study is one of the first reports of QTLs affecting fitness related traits such as leg weakness traits, that segregate within the Landrace population. The study also provides useful information for studying QTLs in purebred populations.     

Safety of alternate-day treatment with TS-1TM (tegafur/gimeracil/oteracil) in tumor-bearing dogs: a pilot study

Tegafur is a prodrug of fluoropyrimidine 5-fluorouracil (5-FU), while TS-1^TM is an oral fixed-dose combination of three active drugs, tegafur, gimeracil, and oteracil. This pilot study evaluated the safety of tegafur/gimeracil/oteracil in the treatment of cancers in dogs. Tegafur/gimeracil/oteracil was administered orally at a mean dose of 1.1 mg/kg twice daily on alternate days, Monday-Wednesday-Friday, every week to 11 dogs with tumors. Partial response and stable disease were observed in one dog each, whereas six exhibited progressive disease. Three dogs were not assessed. Adverse events, the most serious being grade 2, were noted in seven dogs. Adverse events were acceptable, and the drug was effective in some dogs. Therefore, tegafur/gimeracil/oteracil may be useful for treating malignant solid tumors in canines.     

Association of swine vertnin (VRTN) gene with production traits in Duroc pigs improved using a closed nucleus breeding system

Vertnin (VRTN) is involved in the variation of vertebral number in pigs and it is located on Sus scrofa chromosome 7. Vertebral number is related to body size in pigs, and many reports have suggested presence of an association between body length (BL) and meat production traits. Therefore, we analyzed the relationship between the VRTN genotype and the production and body composition traits in purebred Duroc pigs. Intramuscular fat content (IMF) in the Longissimus muscle was significantly associated with the VRTN genotype. The mean IMF of individuals with the wild‐type genotype (Wt/Wt) (5.22%) was greater than that of individuals with the Wt/Q (4.99%) and Q/Q genotypes (4.79%). In addition, a best linear unbiased predictor of multiple traits animal model showed that the Wt allele had a positive effect on the IMF breeding value. No associations were observed between the VRTN genotype and other production traits. The VRTN genotype was related to BL. The Q/Q genotype individuals (100.0 cm) were longer than individuals with the Wt/Q (99.5 cm) and Wt/Wt genotypes (98.9 cm). These results suggest that in addition to the maintenance of an appropriate backfat thickness value, VRTN has the potential to act as a genetic marker of IMF.     

Muscle carbonic anhydrase III levels in normal and muscular dystrophia afflicted chickens

Background

The levels and immunohistochemical localization of muscle carbonic anhydrase III (CA-III) in healthy chickens and in muscular dystrophia affected (DA) chickens show that the muscles of diseased animal undergo a progressive increase of enzyme activity.

Methods

An enzyme-linked immunoassay was used to assess the CA-III levels in the muscles and other tissues from eight normal White Leghorn chickens and in two chickens with muscular dystrophy. Immunohistochemical localization of the enzyme in the muscles of these animals was also determined.

Results

The levels of CA-III in the tensor fasciae latae and the superficial pectoral muscles of the DA chickens were higher than the level in normal chickens. The concentrations of CA-III in erythrocytes and plasma from diseased chickens were approximately 15-fold and 1.4-fold higher than in the normal chickens, respectively. In the superficial pectoral and the tensor fasciae latae muscles of diseased chickens, the numbers of strongly stained and weakly stained fibers were greater than that in the normal chickens.

Conclusion

The levels of CA-III in the superficial pectoral muscle, the tensor fasciae latae muscle, plasma and erythrocytes from the chickens with muscular dystrophy were higher than found in normal chickens.     

Effects of single and repeated heat stress on anxiety-like behavior and locomotor activity in medaka fish

In this study, we examined whether a single heat stress incident and long-term repeated heat stress could affect behavioral and neural responses in male medaka fish Oryzias latipes. By using the novel tank diving test, we found that 7-day repeated heat stress led to anxiety-like behaviors and suppressed locomotor activity, whereas fluoxetine treatment during repeated heat stress led to anxiolytic behaviors. Furthermore, a single heat stress incident increased hyper-locomotor activity. A single heat stress incident decreased mRNA expression of tryptophan hydroxylase 2 (tph2), a rate-limiting enzyme in serotonin biosynthesis, while a single heat stress increased mRNA expression of tyrosine hydroxylase 1 (th1) and tyrosine hydroxylase 2 (th2), catalyzing dopamine biosynthesis in the brain. Plasma cortisol concentration increased after a single stress, repeated stress, and fluoxetine treatment during repeated stress. These results suggest that medaka fish are a good model for assessing anxiety-like behavior induced by long-term repeated stress. Moreover, th1, th2, and tph2 in the brain would be key factors in the exploration of the central regulation of behavioral responses to a single and repeated stress in fish.