The clinical effectiveness of INB in both PROs and disease-activity measures was comparable to INX during the first year of switching, with no immediate safety signals. Subjective reasons (negative expectations) may play a role among discontinuations of biosimilars. Larger patient numbers and longer follow-up are necessary for confirming this clinical experience.

No abstract

The raccoon dog (Nyctereutes procyonoides, Canidae, Carnivora) is a middle-sized omnivore with excessive autumnal fattening and winter sleep. We studied seasonal weight regulation of the species by following the plasma leptin, ghrelin, and growth hormone (GH) levels of farm-bred raccoon dogs (n = 32) for 6 months. In August, half of the raccoon dogs received continuous-release melatonin implants, and in November, half of the animals of both the sham-operated and melatonin-treated groups were fasted for 2 months. In the autumn, the plasma leptin and GH levels were low, but the ghrelin levels were relatively high and correlated positively with energy intake. This represents the period of energy storage. Leptin and GH levels peaked simultaneously in late October, and melatonin advanced the peaks by 1 week. Thereafter, the levels rapidly declined, representing the transition period from autumnal anabolism to wintertime catabolism. In the winter, the leptin and GH levels rose to high levels, but the ghrelin-leptin ratio was very low. This is the period of winter sleep, with fat accumulated in the autumn as the principal metabolic fuel. In the winter, leptin, ghrelin, and GH may work in synergy to increase lipolysis. GH may also induce winter sleep to the raccoon dog. Fasting had no effect on the hormone levels, unlike in humans and rodents. Instead of the amount of fat in the body, the main regulators of the levels of these hormones in the raccoon dog are presumably seasonal rhythms entrained by melatonin.

We assessed the effects of ambient solar ultraviolet (UV) radiation on below-ground parameters in an arctic heath in north-eastern Greenland. We hypothesized that the current UV fluxes would reduce root biomass and mycorrhizal colonization and that these changes would lead to lower soil microbial biomass and altered microbial community composition. These hypotheses were tested on cored soil samples from a UV reduction experiment with three filter treatments (Mylar, 60% UV-B reduction; Lexan, up to 90% UV-B reduction 1 UV-A reduction; UV transparent Teflon, filter control) and an open control treatment in two study sites after 3 years' manipulation. Reduction of both UV-A and UV-B radiation caused over 30% increase in the root biomass of Vaccinium uliginosum, which was the dominant plant species. UV reduction had contrasting effects on ericoid mycorrhizal colonization of V. uliginosum roots in the two sites, while it had no clear effects on fungal (ergosterol) or microbial biomass (measured both with fumigation-extraction and quantitative lipid biomarker analysis) in soil. However, principal component analysis of lipid biomarkers (phospholipid and glycolipid fatty acid profiles) showed that microbial community composition was altered by UV reduction. Although the UV responses were slight considering the large dose difference between the treatments (from near-ambient to up to 90% UV-B reduction), we cannot rule out the possibility that the recovery of ozone layer would change the below-ground functioning of arctic ecosystems.

Plasma leptin and thyroxin concentrations of eleven raccoon dogs and eleven blue foxes were monitored for 6 months. Half of the animals were placed on a 3‐week fast in November. Leptin levels were low in summer, but in October they rose significantly. In November, leptin concentrations decreased rapidly within a week although the body mass of the animals remained stable. There were no significant differences between experimental groups for raccoon dogs, but in blue foxes the fasting group had lower leptin levels than the control group. High thyroxin levels in summer decreased as autumn progressed, but thyroxin concentrations of the fasting groups increased at the end of the fast. Leptin levels of the raccoon dog and the blue fox are not determined only by the fat reserves of the animals, but they seem to reflect the autumnal deposition of fat at the onset of winter. Blue foxes have metabolic rates of active animals during the winter and higher leptin levels in December than raccoon dogs. The superficially hibernating raccoon dogs have low leptin levels after the onset of winter perhaps as an adaptation to fasting. J. Exp. Zool. 289:109–118, 2001. © 2001 Wiley‐Liss, Inc.

The raccoon dog (Nyctereutes procyonoides) is the only canid with passive overwintering in areas with cold winters, but the depth and rhythmicity of wintertime hypothermia in the wild raccoon dog are unknown. To study the seasonal rhythms of body temperature (T(b)), seven free-ranging animals were captured and implanted with intra-abdominal T(b) loggers and radio-tracked during years 2004-2006. The average size of the home ranges was 306+/-26 ha, and the average 24 h T(b) was 38.0+/-<0.01 degrees C during the snow-free period (May-November). The highest and lowest T(b) were usually recorded around midnight (21:00-02:00 h) and between 05:00-11:00 h, respectively, and the range of the 24 h oscillations was 1.2+/-0.01 degrees C. The animals lost approximately 43+/-6% of body mass in winter (December-April), when the average size of the home ranges was 372+/-108 ha. During the 2-9-wk periods of passivity in January-March, the average 24 h T(b) decreased by 1.4-2.1 degrees C compared to the snow-free period. The raccoon dogs were hypothermic for 5 h in the morning (06:00-11:00 h), whereas the highest T(b) values were recorded between 16:00-23:00 h. The range of the 24 h oscillations increased by approximately 0.6 degrees C, and the rhythmicity was more pronounced than in the snow-free period. The ambient temperature and depth of snow cover were important determinants of the seasonal T(b) rhythms. The overwintering strategy of the raccoon dog resembled the patterns of winter sleep in bears and badgers, but the wintertime passivity of the species was more intermittent and the decrease in the T(b) less pronounced.

Eight male and eight female minks were given exogenous melatonin as subcutaneous implants. The plasma leptin and thyroxine concentrations were measured. The leptin concentrations showed clear seasonal variations and differences between the experimental groups. In September most of the control females had undetectable plasma leptin concentrations, but the melatonin-treated females had detectable concentrations significantly higher than the leptin levels of the controls. Most of the males had undetectable leptin concentrations, too. In October the plasma leptin levels had increased significantly in all the groups except the control males. The melatonin-treated minks had significantly higher leptin levels than the controls. There was a significant rise in the thyroxine levels from September to October and the melatonin-treated groups had significantly higher thyroxine levels than the controls. The effects of exogenous melatonin are very pronounced in the mink. Melatonin elevates the plasma leptin and thyroxine levels possibly by direct and indirect mechanisms.

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome characterized by asymptomatic hepatic steatosis. It is present in most cases of human obesity but also caused e.g., by rapid weight loss. The patients have decreased n-3 polyunsaturated fatty acid (PUFA) proportions with decreased percentages of 18:3(n-3), 20:5(n-3) and 22:6(n-3) and an increased n-6/n-3 PUFA ratio in liver and/or white adipose tissue (WAT). The present study examined a new experimental model to study liver steatosis with possible future applications to NAFLD. Ten European polecats (Mustela putorius), the wild form of the domestic ferret, were food-deprived for 5 days with 10 fed animals as controls. The food-deprived animals showed micro- and macrovesicular hepatic steatosis, decreased proportions of 20:5(n-3), 22:6(n-3) and total n-3 PUFA and increased n-6/n-3 PUFA ratios in liver and WAT. At the same time, the product/precursor ratios decreased in liver. The observed effects can be due to selective fatty acid mobilization preferring n-3 PUFA over n-6 PUFA, decreased Delta5 and Delta6 desaturase activities, oxidative stress, decreased arginine availability and activation of the endocannabinoid system. Hepatic lipidosis induced by food deprivation was manifested in the fatty acid composition of the polecat with similarities to human NAFLD despite the different principal etiologies.