Rodent carcinogenesis bioassay with oxisuran, a selective immunosuppressive agent

The carcinogenic potential of oxisuran, a synthetic immunosuppressive agent, was studied for 80 weeks and 104 weeks in mice and rats, respectively. Groups of 50 mice and 70 rats of each sex received oxisuran at doses of 600, 240, and 40 mg/kg/day as dietary admixtures over the entire experimental period. Adequate survival rates allowed accurate statistical analysis of diagnosed neoplasia. Increased susceptibility to tumor development was not clearly demonstrated. In mice the only statistically significant increase in the incidence of malignancy was lung carcinomas in high dose females (P P P P < 0.01) contributed to an overall decrease in both benign tumors and in the combined benign and malignant tumor rates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25114/1/0000547.pd

Electronic Structure, Magnetism and Superconductivity of Layered Iron Compounds

The layered iron superconductors are discussed using electronic structure calculations. The four families of compounds discovered so far, including Fe(Se,Te) have closely related electronic structures. The Fermi surface consists of disconnected hole and electron cylinders and additional hole sections that depend on the specific material. This places the materials in proximity to itinerant magnetism, both due to the high density of states and due to nesting. Comparison of density functional results and experiment provides strong evidence for itinerant spin fluctuations, which are discussed in relation to superconductivity. It is proposed that the intermediate phase between the structural transition and the SDW transition in the oxy-pnictides is a nematic phase.Comment: Proceedings ISS200

Discrimination of Food Amounts by the Domestic Dog (Canis familiaris)

The current research examined the ability of dogs to discriminate between different amounts of food. Using a two-alternative-forced-choice procedure, dogs were required to discriminate between a constant amount of 4 pieces of food and another amount that varied across a range from 1 to 7 pieces. The dogs reliably selected the larger of the two alternatives. Discrimination was better when there were fewer than rather than more than 4 pieces of food available on the varying alternative. Specifically, 1 piece was discriminated from 4 pieces more easily than 4 pieces were discriminated from 7 pieces of food. These results confirmed the ability of dogs to discriminate food amount on a psychophysical choice procedure. This research addresses a question fundamental to theories of reinforcement of why reinforcer magnitude does not always control behavior in an intuitive way. We argue that the relative difficulty of discriminating smaller from larger amounts of food is an important factor in understanding the impact of reinforcer magnitude in the development of reinforcer control over behavio

Inter-rater reliability of the Dysexecutive Questionnaire (DEX): comparative data from non-clinician respondents – all raters are not equal

Primary objective: The Dysexecutive Questionnaire (DEX) is used to obtain information about executive and emotional problems after neuropathology. The DEX is self-completed by the patient (DEX-S) and an independent rater such as a family member (DEX-I). This study examined the level of inter-rater agreement between either two or three non-clinician raters on the DEX-I in order to establish the reliability of DEX-I ratings. Methods and procedures: Family members and/or carers of 60 people with mixed neuropathology completed the DEX-I. For each patient, DEX-I ratings were obtained from either two or three raters who knew the person well prior to brain injury. Main outcomes and results: We obtained two independent-ratings for 60 patients and three independent-ratings for 36 patients. Intra-class correlations revealed that there was only a modest level of agreement for items, subscale and total DEX scores between raters for their particular family member. Several individual DEX items had low reliability and ratings for the emotion sub-scale had the lowest level of agreement. Conclusions: Independent DEX ratings completed by two or more non-clinician raters show only moderate correlation. Suggestions are made for improving the reliability of DEX-I ratings.</p

Carcinogenicity studies in rodents with ripazepam, a minor tranquilizing agent

The carcinogenesis potential of ripazepam, a benzodiazepine derivative, was studied in mice and rats for 78 and 104 weeks, respectively. Groups of 50 male and 50 female CD1 mice and CD rats each were given doses of 15 and 150 mg/kg of ripazepam in the diet. Survival rates were adequate for statistical analysis. Significant suppression of body weight gains occurred in rats but not in mice given 150 mg/kg/day. The compound failed to increase tumor rates or alter the average latency of neoplasms in the rat. In mice, the number of male animals with tumors was increased at 150 mg/kg and this was related to a significant increase in the number of animals with hepatocellular tumors. Hepatocellular tumors were increased also in female mice but the increase was not statistically significant. All but one of these hepatic neoplasms were hepatocellular adenomas and the one carcinoma had not metastasized. Other tumor types were not increased.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24852/1/0000279.pd

P2Y Receptors Sensitize Mouse and Human Colonic Nociceptors

Activation of visceral nociceptors by inflammatory mediators contributes to visceral hypersensitivity and abdominal pain associated with many gastrointestinal disorders. Purine and pyrimidine nucleotides (e.g., ATP and UTP) are strongly implicated in this process following their release from epithelial cells during mechanical stimulation of the gut, and from immune cells during inflammation. Actions of ATP are mediated through both ionotropic P2X receptors and metabotropic P2Y receptors. P2X receptor activation causes excitation of visceral afferents; however, the impact of P2Y receptor activation on visceral afferents innervating the gut is unclear. Here we investigate the effects of stimulating P2Y receptors in isolated mouse colonic sensory neurons, and visceral nociceptor fibers in mouse and human nerve-gut preparations. Additionally, we investigate the role of Na(v)1.9 in mediating murine responses. The application of UTP (P2Y(2) and P2Y(4) agonist) sensitized colonic sensory neurons by increasing action potential firing to current injection and depolarizing the membrane potential. The application of ADP (P2Y(1), P2Y(12), and P2Y(13) agonist) also increased action potential firing, an effect blocked by the selective P2Y(1) receptor antagonist MRS2500. UTP or ADP stimulated afferents, including mouse and human visceral nociceptors, in nerve-gut preparations. P2Y(1) and P2Y(2) transcripts were detected in 80% and 56% of retrogradely labeled colonic neurons, respectively. Na(v)1.9 transcripts colocalized in 86% of P2Y(1)-positive and 100% of P2Y(2)-positive colonic neurons, consistent with reduced afferent fiber responses to UTP and ADP in Na(v)1.9(−/−) mice. These data demonstrate that P2Y receptor activation stimulates mouse and human visceral nociceptors, highlighting P2Y-dependent mechanisms in the generation of visceral pain during gastrointestinal disease. SIGNIFICANCE STATEMENT Chronic visceral pain is a debilitating symptom of many gastrointestinal disorders. The activation of pain-sensing nerves located in the bowel wall and their sensitization to physiological stimuli, including bowel movements, underpins the development of such pain, and is associated with mediators released during disease. This work addresses the unstudied role of purine and pyrimidine nucleotides in modulating colonic nociceptors via P2Y receptors using a combination of electrophysiological recordings from human ex vivo samples and a detailed functional study in the mouse. This is the first report to identify colonic purinergic signaling as a function of P2Y receptor activation, in addition to established P2X receptor activity, and the results contribute to our understanding of the development of visceral pain during gastrointestinal disease

Workshop on Feedback Stabilization of MHD Stabilities

The feedback stabilization of MHD instabilities is an area of research that is critical for improving the performance and economic attractiveness of magnetic confinement devices. A Workshop dedicated to feedback stabilization of MHD instabilities was held from December 11-13, 1996 at the Princeton Plasma Physics Laboratory, Princeton NJ, USA. The resulting presentations, conclusions, and recommendations are summarized

Evaluation of chronic toxicity and carcinogenesis in rodents with the synthetic analgesic, tilidine fumarate

The carcinogenic potential of tilidine fumarate, a synthetic analgesic, was studied for 80 and 104 weeks in mice and rats, respectively. Groups of 50 albino CF1 mice and 65 albino Wistar rats of each sex received tilidine fumarate-lactose blend (1:1) at doses of 100, 40 and 16 mg/kg. The control groups consisted of 100 mice and 115 rats of each sex and received the lactose vehicle only. Treatment-related non-neoplastic changes consisted of reversible, increased cytoplasmic eosinophilia of hepatocytes in high and mid dose rats corresponding to areas of proliferating smooth endoplasmic reticulum; and an increased in high dose rats of proliferative or cystic lesions of the biliary epithelium. Adequate survival rates allowed stringent statistical analysis of neoplasia. Tilidine did not evoke increased tumor incidences or changes in teh average latency or onset of tumors in either species. The most frequent tumors represented spontaneous neoplasia characteristic of historical background incidence in these strains. In mice, the only statistically significant (P P &lt; 0.01) decreased incidences of mammary fibroadenoma and pituitary adenoma. From these data, it was concluded that the synthetic analgesic tilidine does not possess tumorigenic potential in rodents.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26174/1/0000253.pd