Effects of Thiopental, Ketamine, Diazepam, Xylazine, and Nitrous Oxide on EEG Spike Activity and Convulsive Bfehavior During Enflurane Anesthesia in Spontaneously Breathing Atropinized Cats Effect at Surgical Depth

The effects of thiopental, ketamine, diazepam, xylazine and nitrous oxide, and combinations of thiopental-nitrous oxide and ketamine-nitrous oxide on electroencephalographic (EEG) spike activity and convulsive behaviors in atropinized cats at surgical depth of enflurane anesthesia were assessed quantitatively for 60 minutes during spontaneous ventilation. Mean inspired enflurane concentrations (MIEC) were reduced 16% to 29% by pretreatment with thiopental, ketamine, diazepam, and xylazine, and were reduced 19% by 66% nitrous oxide. The MIEC of cats anesthetized with thiopental-nitrous oxide-enflurane and ketamine-nitrous oxide-enflurane were 35% to 38% lower than that with nitrous oxide-enflurane. Pretreatment with thiopental, ketamine, diazepam, and xylazine did not reduce the EEG spike frequency during anesthesia but did markedly reduce the spike amplitude. The addition of 66% nitrous oxide did not alter the spike frequency during anesthesia but tended to reduce the spike amplitude. Combinations of thiopental-nitrous oxide and ketamine-nitrous oxide almost abolished the spike activity. The addition of 66% nitrous oxide prevented convulsive responses elicited by photic and auditory stimulation during enflurane anesthesia. Treatment with thiopental, ketamine, diazepam and xylazine, and combinations of thiopental-nitrous oxide and ketamine-nitrous oxide, completely prevented convulsive responses during enflurane anesthesia.     

The increment of anti-ORP150 autoantibody in initial stages of atheroma in high-fat diet fed mice

Expression of 150 kda oxygen-regulated protein, ORP150, was examined in the atheromatous lesions on aortic valves in high-fat diet fed mice. Immunohistochemical staining revealed that ORP150 was expressed on the surface of plaque and was co-localized with phagocytes bearing Mac-3, a mouse macrophage differentiation antigen. These findings suggest that ORP150 is involved in the development of the atheromatous plaque. Titer of autoantibody against ORP150 was gradually elevated in parallel with the length of period of high-fat diet feeding. These results suggest that the deposition of immunocomplex toward ORP150 antigen is involved in atheromatous plaque progression.     

Lack of Hepatocarcinogenicity of Combinations of Low Doses of 2-amino-3, 8-dimethylimidazo[4,5- f ]quinoxaline and Diethylnitrosamine in Rats: Indication for the Existence of a Threshold for Genotoxic Carcinogens

The purposes of the present study were to evaluate the hepatocarcinogenicity of concurrent treatment of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and diethylnitrosamine (DEN) in rats and to determine whether no effect levels of combinations of these two different structural categories of genotoxic hepatocarcinogens exist. Two 16-week rat hepatocarcinogenesis assays were performed using a total of 790 male F344 rats. In experiment 1, we evaluated the effects of concurrent treatment of a subcarcinogenic dose of DEN on rat hepatocarcinogenesis induced by various doses of MeIQx. In experiment 2, we determined hepatocarcinogenicities of combinations of MeIQx and DEN at subcarcinogenic doses, low carcinogenic doses and high carcinogenic doses. Quantitative analyses of glutathione S-transferase placental form (GST-P)-positive foci, a preneoplastic lesion of the liver in rats, revealed that concurrent treatment with subcarcinogenic doses of DEN did not enhance MeIQx-induced rat hepatocarcinogenicity. We also found that concurrent treatment with combinations of subcarcinogenic doses of DEN and MeIQx was not hepatocarcinogenic, indicating that the combined effects of subcarcinogenic doses of DEN and MeIQx were neither additive nor synergistic. Moreover, concurrent treatment with low carcinogenic doses of these 2 carcinogens did not show additive or synergistic effects. Synergetic effects were observed only in rats coadministered high carcinogenic doses of the 2 carcinogens. These results demonstrate the existence of no effect levels of combinations of these 2 genotoxic hepatocarcinogens, and provide new evidence supporting our idea that there is a threshold, at least a practical threshold, that should be considered when evaluating the risk of genotoxic carcinogens.     

Genotypes and allele frequencies of buried SNPs in a bovine single‐nucleotide polymorphism array in Japanese Black cattle

Single nucleotide polymorphism (SNP) arrays are widely used for genetic and genomic analyses in cattle breeding; thus, data derived from SNP arrays have accumulated on a large scale nationwide. Commercial SNP arrays contain a considerable number of unassigned SNPs on the chromosome/position on the genome; these SNPs are excluded in subsequent analyses. Notably, the position‐unassigned SNPs, or “buried SNPs” include some of the markers associated with genetic disease. In this study, we identified the position of buried SNPs using the Basic Local Alignment Search Tool against the surrounding sequences and characterized the relationship between SNPs and genetic diseases in Online Mendelian Inheritance in Animals based on the genomic position. We determined the position of 285 buried SNPs on the genome and surveyed the genotype and allele frequencies of these SNPs in 5,955 individual Japanese Black cattle. Eleven SNPs associated with genetic disease, which contained five buried SNPs, were found in the population with the risk allele frequency ranging from 0.00008396 to 0.46. These results indicate that buried SNPs in the bovine SNP array can be utilized to identify associations with genetic disorders from large scale accumulated SNP genotype data in Japanese Black cattle.     

Enhanced Urinary Bladder, Liver and Colon Carcinogenesis in Zucker Diabetic Fatty Rats in a Multiorgan Carcinogenesis Bioassay: Evidence for Mechanisms Involving Activation of PI3K Signaling and Impairment of p53 on Urinary Bladder Carcinogenesis

In the present study, modifying effects of diabetes on carcinogenesis induced in type 2 diabetes mellitus model Zucker diabetic fatty (ZDF) rats were investigated using a multiorgan carcinogenesis bioassay. Our re sults demonstrated enhancement of urinary bladder, colon and liver carcinogenesis in ZDF rats treated with five types of carcinogens (DMBDD). Elevated insulin and leptin and decreased adiponectin levels in the serum may be responsible for the high susceptibility of type 2 diabetes mellitus model rats to carcinogenesis in these organs. Possible mechanisms of increased susceptibility of diabetic rats to bladder carcinogenesis could be activation of the PI3K pathway and suppression of p53 in the urothelium in consequence of the above serum protein alterations.     

Analysis of preference for domestic grass‐fed beef in Japanese youths

A questionnaire based on sensory evaluation of completely domestic grass‐fed beef was carried out on 157 Japanese undergraduate students aged between 18 and 22 years in Kitasato University. The sensory evaluation sheet consisted of 10 questions concerning preference for domestic grass‐fed beef, and three demographic/lifestyle questions. Using principal component analysis and cluster analysis, the respondents were divided into four groups (G1–G4). G1 accepted almost all properties. G2 accepted most properties but disliked chewiness. G3 accepted juiciness and flavor but disliked the color and texture of the meat. G4 tended to dislike almost all properties. According to chi‐square test, most G2‐people statistically liked other commercial beef and G4‐people had neutral and negative impressions. G1‐ or G3‐people did not have any significant tendency as regards beef preference. These results indicate that most of the young respondents who preferred domestic grass‐fed beef could not accept its texture, and some respondents could accept its juiciness and flavor. It is also suggested that a part of the people who like commercial beef do not prefer chewiness of grass‐fed beef. Such information will aid grass‐fed beef cattle breeders, producers and packers to improve the quality of beef and its evaluation.     

Ethanol Does Not Promote MeIQx-initiated Rat Colon Carcinogenesis Based on Evidence from Analysis of a Colon Cancer Surrogate Marker

Epidemiological studies suggest that alcohol consumption increases the risk of developing colorectal cancer. However, the data are confounded by numerous cosegregating variables. To cast further light on the relationships between alcohol intake and colon cancer development, 21-day-old male F344/DuCrj rats were fed 200 ppm 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in their diet for 8 weeks and doses of 0, 0.1, 0.3, 1, 3, 10 and 20% of ethanol in their drinking water ad libitum for 16 weeks thereafter. The rats were sacrificed after 24 weeks of experiment, and aberrant crypt foci (ACF), surrogate lesions for colon cancer, were examined under a light microscope at low magnification. Ethanol was found not to affect the ACF formation at any dose compared with the initiated-controls. Furthermore, ethanol did not alter colon epithelial cell proliferation. These data, obtained by analysis of a colon cancer surrogate marker lesion, indicate that ethanol lacks promotion activity for MeIQx-initiated rat colon carcinogenesis.