The effect of REM sleep deprivation on histamine concentrations in different brain areas.

Rats were deprived of REM sleep (REMS) for 72 h with the platform method and decapitated in the morning immediately after the deprivation or in the afternoon after having been allowed 5 hours of rebound sleep. The histamine concentrations of the anterior and posterior hypothalamus, the cortex, the hippocampus and the pineal gland were measured, as well as the tele-methylhistamine concentrations of the anterior and posterior hypothalamus. Histamine concentrations were no different after REMS deprivation compared to large platform or dry cage controls, but in the anterior hypothalamus histamine levels increased during rebound sleep only in the REMS deprived rats. tele-Methylhistamine/histamine ratios were higher after 72 h of both REMS deprivation and the large platform treatment compared to dry cage controls, indicating increased histamine utilization during the platform treatment procedure.

Analysis of (dichloromethylene) bisphosphonate in urine by capillary gas chromatography-mass spectrometry.

An anion exchange extraction method of bisphosphonates from urine is described. More than 90% of the (dichloromethylene) bisphosphonate (Cl2MBP, clodronate) was recovered from urine. The extracted bisphosphonates were trimethylsilylated and analysed with capillary gas chromatography-mass spectrometry (GC/MS). The mass spectrometric techniques used were electron ionization (EI), ammonia chemical ionization (CI), ammonia CI tandem mass spectrometry and methane negative chemical ionization (NCI). The limit of detection of Cl2MBP was 25 pg/injection in the NCI/selective ion recording (SIR)-mode. At 100 ng ml-1 of Cl2MBP the precision of the whole assay method was 17.9% (N = 6). The NCI/SIR technique offers a sensitive and highly selective method for the quantitation of Cl2MBP in urine.

Tissue distribution and elimination of perfluorodecanoic acid in the rat after single intraperitoneal administration.

Tissue distribution, metabolism, and excretion of perfluorodecanoic acid (PFDA) after a single intraperitoneal dose (20 mg/kg) were studied in female and male Wistar rats. PFDA accumulated in the serum and tissues of the rats. In the serum, more than 99% of PFDA was bound by the serum proteins. In the liver, anionic and esterified PFDA were detected. Metabolic oxidation of PFDA was not observed. PFDA was not excreted in urine either by females or males during 14 days after the administration. At the same time, about 0.5% of the administered PFDA dose was excreted daily in the faeces by both sexes. In spite of the analogical structure with perfluorooctanoic acid (PFOA), which is rapidly eliminated in urine by the female rats, PFDA accumulated similarly in females and males. The reduced elimination of PFDA partially explains its greater toxicity to rats in comparison with PFOA.

Effect of increasing ruminal butyrate on milk yield and blood constituents in dairy cows fed a grass silage-based diet.

The effects of increased ruminal supply of butyrate on milk yield, milk composition, and blood metabolites were studied in four lactating cows in a 4 x 4 Latin square design. The basal diet comprised grass silage, hay, and concentrate (34:22:42, DM basis) and was supplemented with isoenergetic VFA infusions (3.58 Mcal/d). A 3:1 molar mixture of acetate and propionate was replaced gradually with butyrate at the rates of 0, 200, 400, or 600 g/d. When the amount of infused butyrate increased, isobutyrate, butyrate, and isovalerate in plasma and acetoacetate and beta-hydroxybutyrate in whole blood increased linearly, but plasma glucose concentration decreased. The latter was associated with a trend toward higher plasma urea concentration, suggesting that more AA were used for gluconeogenesis as the supply of propionate decreased and that of butyrate increased. Milk yield was not changed. The concentrations of milk fat and protein increased, and that of lactose decreased linearly, with the rate of butyrate infusion. Milk fat yield increased, and lactose yield tended to decrease, with increased butyrate infusion. These results indicate that changes in the supply of butyrate do not affect markedly milk yield in cows yielding less than 20 kg/d but cause marked changes in milk composition. The increase in ruminal butyrate supply increased ketogenesis and decreased gluconeogenesis in the liver of lactating dairy cows.

Toxicity and kinetics of perfluoro-octanoic acid in the Wistar rat.

Perfluoro-octanoic acid [PFO; CF3 (CF2)6 COOH] is a single chain fatty acid with surfactant properties. Thus far the kinetics and toxicity of PFO has not been studied thoroughly. PFO was administered orally 3 mg/kg, 10 mg/kg, and 30 mg/kg to 36 Wistar rats daily for 28 consecutive days. Another 12 animals received 0.5 ml/100 g saline each day. Animal behaviour, body weight, as well as, water and food consumption were observed regularly. Blood, urine, and some viscera were collected for the analysis of PFO and histopathology. Food consumption decreased with increasing dose of PFO. Serum PFO concentrations were 6-19 times higher in the males than in the females (range 48.6-83.0 micrograms/ml males, and 2.4-11.2 micrograms/ml females) (p less than 0.001). On the 7th day the mean PFO excretion in the low dose group for the males was 157 +/- 63 micrograms/24 (SD) h and 255 +/- 27 micrograms/24 h for females (p less than 0.05). In the high dose group the corresponding figures were 2476 +/- 665 micrograms/24 h (males) and 2917 +/- 493 micrograms/24 h (females). On the 28th day the PFO excretion for the low dose males was 609 +/- 87 micrograms/24 h, 671 +/- 65 micrograms/24 h for the females. In the high dose group the figures were 4619 +/- 2886 micrograms/24 h (males) and 4379 +/- 692 micrograms/24 h (females).

Elimination and toxicity of perfluorooctanoic acid during subchronic administration in the Wistar rat.

Perfluorinated fatty acids have been used commercially as corrosion inhibitors, wetting agents, fire extinguishers and surface active agents. In an earlier study the male rats were more susceptible to the toxic effects of perfluorooctanoic acid (PFO) than females. PFO-concentrations in the plasma suggested that there was a sex related difference in the urinary elimination rate. Active tubular secretion was observed only in the female kidney. The aim of the present study was to compare the urinary elimination of PFO between the two sexes during subchronic administration to the Wistar rat. PFO was administered by gavage to 48 newly-weaned animals at 0 mg/kg, 3 mg/kg, 10 mg/kg and 30 mg/kg for 28 consecutive days. The urine was collected on the 7th and 28th day of the study. At the end of the study, blood was collected by cardiac puncture. At necropsy, tissue specimens for histopathologic examination were collected from the controls and from the group receiving 30 mg/kg of PFO daily. Unlike the female rats, on the 7th day of the study all three groups of male rats excreted significant less PFO than their daily dose of PFO, which suggested that the males had not reached a steady state by seven days. On the 28th day, the males excreted an amount of PFO equal to their daily dose. The PFO concentrations in the plasma of the male animals suggested that the binding sites of PFO may become saturated at the chronic daily dose level of 30 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Stimulation by oestradiol of the urinary excretion of perfluorooctanoic acid in the male rat.

The urinary excretion of perfluorooctanoic acid (PFOA) was studied in male Wistar rats after castration and oestradiol administration as well as in intact females and males. During the first 24 hr females excreted 72 +/- 5% (N = 6) of a single intraperitoneal dose of PFOA (50 mg/kg) in urine whereas the intact males excreted only 9 +/- 4% (N = 6). After castration followed by oestradiol administration (500 micrograms/kg every 2nd day for 14 days), the males excreted PFOA in urine in similar amounts as the females (68 +/- 14% at 24 hr, N = 10). Oestradiol treatment of non-castrated males produced similar results (61 +/- 19% at 24 hr, N = 10). Also castration without oestradiol administration significantly enhanced the renal PFOA excretion, but not as effectively as oestradiol treatment. After 96 hr, the concentration of PFOA in serum of intact males was 17-40 times higher than in the serum of other groups. PFOA was similarly bound by the proteins in the serum of females and males. Phase II metabolism of PFOA was not shown either in males or females.

Studies on the role of lipid peroxidation in the acute toxicity of TCDD in rats.

Lipid peroxidation has been shown to be enhanced following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), but its role in TCDD toxicity is unclear. The present study was undertaken to further elucidate the relations between lipid peroxidation and TCDD lethality. A time course and dose-response experiment in Long-Evans (L-E; LD50 ca. 10 micrograms/kg) and Han/Wistar (H/W; LD50 greater than 3000 micrograms/kg) rats showed that hepatic lipid peroxidation, measured as the amount of thiobarbituric acid-reactive substances (TBA-RS), was induced by TCDD dose-dependently in L-E, but not in H/W rats. Hepatic glutathione peroxidase activity was suppressed in much the same manner in both strains. Lipid peroxidation correlated with body weight loss in L-E rats alone. When 500 micrograms/kg of TCDD was given to L-E rats, lipid peroxidation increased about 3-fold on Day 11 in the liver, while no change was seen in cardiac or renal TBA-RS. The pair-fed controls did not survive the 11-day test period and exhibited gastrointestinal hemorrhages. At 6 days, liver atrophy and elevated (over 2-fold) TBA-RS values were recorded in pair-fed controls but not in their TCDD-treated counterparts. TCDD decreased hepatic glutathione peroxidase activity by almost 50% at 6 days, while pair-feeding was without effect. Liver morphology was different between TCDD-treated and pair-fed rats. Moreover, the livers of TCDD-treated L-E rats contained much higher concentrations of probably peripheral fat-derived fatty acids than did the livers of pair-fed or ad libitum control rats. Restricted feeding over 6 days induced hepatic lipid peroxidation more in H/W than in L-E rats. Endotoxin increased liver TBA levels similarly in both strains having an additive effect with high doses of TCDD in H/W rats. Added as a 0.5% concentration in chow, butylated hydroxyanisole (BHA), but not ethoxyquin, tended to increase survival rate and time in L-E rats exposed to 20 micrograms/kg of TCDD; at 50 micrograms/kg the only survivor was again in the BHA group. However, neither antioxidant had any effect on initial body weight loss. It is concluded that lipid peroxidation mainly arises as a secondary phenomenon in TCDD toxicity, is not the cause of the typical histopathological liver lesion, but may contribute to lethality.