Carbon Dioxide Production by Individual Mice as an Index of Behavioral and Metabolic Activity

Carbon Dioxide Production in Individual Mice as an Index ofBehavioral and Metabolic Activity. BUSHNELL, P. J., EVANS, H.L., AND PALMES, E. D. (1985). Fundam. Appl. Toxicol.. 5,962-970.A noninvasive method for simultaneous real-time determinationof spontaneous locomotor activity (LA) and CO₂ production (asminute volume expired CO₂, or _ECO₂) in miceis described. As an apical measure of overall metabolic activity,_ECO₂ proved sensitive to changes in manyphysiological processes, including behavioral activity. In normalmice, LA (as photobeam breaks) and _ECO₂ werepositively correlated (r = 0.73), and stable over repeated dailytests. Food deprivation for 18 hr overnight increased LA whiledecreasing _ECO₂. Stimulation of peripheralsympathetic activity, either by exposure to cold air or by injectionof epinephrine, increased _ECO₂ without affectingLA. Intoxication with pentobarbital produced a biphasic changein both measures: anesthetic doses increased LA and _ECO₂ during induction and recovery, and reduced themduring the period of anesthesia itself. These results characterize_ECO₂ as an easily quantifiable, compositeindex of behavioral and metabolic activity in mice. This measure,along with its covariation with LA, may provide better informationabout toxic effects than any single screening test.     

X-radiation induces 8-hydroxy-2'-deoxyguanosine formation in vivo in rat mammary gland DNA

Ionizing radiation is a carcinogen that induces oxidative DNA damage. 8- Hydroxy-2'-deoxyguanosine (8-OHdG) is a relatively abundant, mutagenic lesion that is widely regarded as a reliable index of oxidative DNA damage. The purpose of this study was to examine the effects of X- radiation on levels of 8-OHdG in the context of an experimental model for breast cancer in which chronic radiation exposure has been shown to be carcinogenic in Sprague-Dawley rats. A secondary objective of this study was to determine if the use of phenol during DNA isolation affected the concentration of 8-OHdG subsequently measured. Our results indicate that a profoundly carcinogenic dose of radiation induced a small but significant increase in 8-OHdG concentration in mammary gland DNA, and that the use of a phenol-based versus a salt-based method of DNA isolation had no significant impact on the levels of 8-OHdG detected in either control or irradiated tissue.      

Fructose-Sorbitol Malabsorption and Symptom Provocation in Irritable Bowel Syndrome: Relationship to Enteric Hypersensitivity and Dysmotility

Background: Fructose-sorbitol (F-S) mixtures can provoke symptoms in irritable bowel syndrome (IBS) patients, and a proportion of IBS patients also have enteric hypersensitivity to distension. We hypothesized, therefore, that sugar malabsorption and fermentation to produce hydrogen gas may provoke symptoms to a greater extent in IBS patients hypersensitive to distension than in those patients without such hypersensitivity. Our aims were therefore to compare, in IBS patients, symptoms and breath hydrogen responses after F-S, on the basis of jejunal sensitivity and jejunal motor function. Methods     

Clinical variability of Fanconi anemia (type C) results from expression of an amino terminal truncated Fanconi anemia complementation group C polypeptide with partial activity

Fanconi anemia (FA) is an autosomal recessive disease characterized by congenital anomalies, aplastic anemia, and cancer susceptibility. Mutations within the FA complementation group C (FAC) gene account for approximately 14% of diagnosed FA cases. Two mutations, one in exon 1 (delG322) and one in exon 4 (IVS4 + 4 A to T), account for 90% of known FAC mutations. The delG322 mutation results in a mild FA phenotype, while the IVS4 + 4 A to T mutation results in severe FA phenotype. To determine the molecular basis for this clinical variability, we analyzed patient-derived cell lines for the expression of characteristic mutant FAC polypeptides. All cell lines with the delG322 mutation expressed a 50-kD FAC polypeptides, FRP-50 (FAC-related protein), shown to be an amino terminal truncated isoform of FAC reinitiated at methionine 55. All cell lines with the IVS4 + 4 A to T mutation lacked FRP-50. Overexpression of a cDNA encoding FRP-50 in an FA(C) cell line resulted in partial correction of mitomycin C sensitivity. In conclusion, expression of an amino terminal truncated FAC protein accounts, at least in part, for the clinical heterogeneity among FA(C) patients.     

Is pregnancy a time of changing drinking and smoking patterns for fathers as well as mothers? An initial investigation

This paper describes changing smoking and drinking patterns before and during pregnancy in 313 expectant couples. Fathers were more likely to drink and smoke more heavily than mothers throughout. Before pregnancy in only 42% of couples were both partners safe drinkers and non-smokers. This increased to 50% during pregnancy. Most mothers reduced alcohol consumption during pregnancy and although about half of the fathers also changed their drinking patterns, only about a fifth decreased their consumption. Levels of paternal and maternal drinking in pregnancy were positively associated with pre-pregnancy levels. Rates and levels of both maternal and paternal smoking declined in pregnancy. There was a positive association between partners of both the prevalence and level of drinking and smoking between fanners. There was some indication that mothers were more likely to reduce smoking and drinking if their partner joined them in doing so. Risk drinking in couples was more common in those who were older and of higher social status, but smoking was more common among the younger couples of lower social status.     

Serum interleukin-8 in inflammatory bowel disease

To investigate the relationship between serum concentrations of interleukin-8 (IL-8) and disease activity in inflammatory bowel disease, serum IL-8 concentrations were measured by enzyme-linked immunosorbent assay (ELISA) in 93 patients. Interleukin-8 levels were compared with plasma interleukin-6 (IL-6) levels in 80 of these patients. Interleukin-8 levels were also measured in ten patients with active Crohn's disease, before and after treatment with a defined formula polymeric diet. Of these patients, 70 out of 93 IL-8 concentrations were below the detection limit of the assay. Levels were higher in patients with active ulcerative colitis (median < 20 pg/mL, 75th centile value = 190) compared with inactive disease (median and 75th centile value < 20; P 0.05). Interleukin-8 concentrations correlated with a combined score for disease severity and extent (P= 0.01). Thirty-eight per cent (8/20) of patients with active Crohn's disease also had high levels of IL-8 but there was no significant difference between active and inactive disease. There was no correlation between serum IL-8 and plasma IL-6; on the contrary, very few patients had raised blood levels of both cytokines. In the diet treated group, serum IL-8 fell significantly after treatment (median = 37 pg/mL, range < 20–4615 before treatment, median < 20, range < 20–104 after treatment; P= 0.03). The results suggest that although IL-8 may be involved in the inflammatory process in inflammatory bowel disease, it is a poor marker of disease activity.