The hepatic transport of bile acid conjugates was studied in the Eisai hyperbilirubinuria rat, a Sprague-Dawley mutant rat with conjugated hyperbilirubinemia. Serum bile acid levels were increased, bile acid-independent bile flow was decreased and biliary glutathione concentrations were markedly decreased in the Eisai hyperbilirubinuria rat. Biliary excretion of sulfobromophthalein was markedly impaired and almost no glutathione conjugate was excreted in the bile of the Eisai hyperbilirubinuria rat. Biliary excretion of lithocholate-3-O-glucuronide and lithocholate-3-sulfate in the Eisai hyperbilirubinuria rat was markedly delayed, whereas that of lithocholate was only slightly delayed. After [14C]chenodeoxycholate infusion (1 mumol/min/100 gm for 60 min), the increases in bile flow and biliary excretion of isotope in the Eisai hyperbilirubinuria rat were not so prominent as those observed in control rats, and the glucuronide of chenodeoxycholate, which constituted about 15% of biliary chenodeoxycholate in control rats, was not observed in the Eisai hyperbilirubinuria rat. Initial uptake of lithocholate and its glucuronide and sulfate by isolated hepatocytes was not impaired in the Eisai hyperbilirubinuria rat; the profiles of cytosolic bile acid binding proteins in Eisai hyperbilirubinuria rat liver were identical to those in control liver. These data indicate that the Eisai hyperbilirubinuria rat has excretory impairment of organic anions, bile acid glucuronide and sulfate and that it has characteristics very similar to those of the hyperbilirubinemic mutant Wistar rats TR- and GY.

The paracetamol absorption technique, a widely used method for evaluating the gastric emptying rate of liquids, appears to be performed inappropriately, resulting from a lack of consideration of pharmacokinetics in paracetamol absorption. This review suggests that appropriate study designs and logical choice of the parameters for the rate of paracetamol absorption are the cornerstone of reliable investigation of gastric emptying using the paracetamol method.

In this simple and direct method for determining total bile acids in serum, the serum was mixed with sodium pyruvate, a lactate dehydrogenase blocker, and bile acids were then measured spectrophotometrically after the following enzyme reaction. Bile acids are converted to 3-oxo bile acids with 3 alpha-hydroxysteroid dehydrogenase (EC 1.1.1.50) with concomitant reduction of NAD+ to NADH. The hydrogen in the NADH generated is transferred by diaphorase (EC 1.6.4.3) to nitrotetrazolium blue to yield diformazan 540 nm). Analytical recovery of the various bile acids in serum averaged 96.2%. The CV for the day-to-day variation was 4.3%. Normal values are less than 7 mumol/L. Total serum bile acids were estimated by this method in 118 fasting patients with various liver diseases. This determination is clearly shown to be useful as a liver-function test.

Knowing the reproductive characteristics of a species is essential for the appropriate conservation and management of wildlife. In this study, we investigated the demographic parameters, including age of primiparity, litter size, inter-birth interval, reproductive rate, and cub survival rate, of Hokkaido brown bears (Ursus arctos yesoensis) in the Rusha area on the Shiretoko Peninsula, Hokkaido, Japan, based on a long-term, individual-based monitoring survey. A total of 15 philopatric females were observed nearly every year from 2006 to 2016, and these observations were used to estimate reproductive parameters. The mean age of primiparity was 5.3 ± 0.2 (SE) years (n = 7, 95% CI = 5.0–5.6). We observed 81 cubs in 46 litters from 15 bears. Litter size ranged from one to three cubs, and averaged 1.76 ± 0.08 (SE) cubs/litter (95% CI = 1.61–1.91). Inter-birth intervals ranged from 1 to 4 years, and the mean value was estimated as 2.43 (95% CI = 2.16–2.76) and 2.53 (95% CI = 2.26–2.85) years in all litters and in litters that survived at least their first year, respectively. The reproductive rate was estimated from 0.70 to 0.76 young born/year/reproductive adult female, depending on the method of calculation. The cub survival rate between 0.5 and 1.5 years ranged from 60 to 73%. Most cub disappearances occurred in July and August, suggesting that cub mortality is mainly due to poor nutrition in the summer. All reproductive parameters observed in the Rusha area on the Shiretoko Peninsula fell within the range reported in Europe and North America, and were among the lowest or shortest age of primiparity, litter size, and inter-birth intervals, and ranked at a high level for reproductive rate.

Irruptions of ungulate populations have been observed, but little is known of their cause of initiation and termination. We documented an irruption of a naturally colonizing sika deer (Cervus nippon) population on Cape Shiretoko, Shiretoko Peninsula, northeastern Hokkaido, Japan, and we examined limiting factors on population growth. The population increased from 54 deer in 1986 to 592 deer in 1998 (11 to 118 deer/km2, respectively) and declined to 177 (35 deer/km2) the following winter of 1999. The intrinsic rate of increase from 1986 to 1998 was 0.19 (95% CI: 0.16 to 0.22). We estimated an annual survival for adult females of 0.92. The ratio of calves to adult females was 76%. We observed a density‐correlated reduction in winter food resources. Density‐dependent food resources and their interaction with climatic factors were the most important limiting factors for sika deer. The population recovered rapidly following the population crash in 1999 and increased to 512 deer (102 deer/km2) in 2002. We anticipate further increase and a second crash. To confirm whether the population will be regulated naturally and to establish sika deer management policy in Shiretoko National Park, long‐term monitoring of the relationship between sika deer and their habitat must be implemented.

A total of 32 wild Hokkaido sika deer ( Cervus nippon yesoensis ) were shot (13 in summer, nine in autumn and 10 in winter) in the Syari district, Shiretoko Peninsula of Hokkaido Island, Japan. The ingested foods, rumen fermentation parameters and microbes were determined to evaluate digestive strategy and food availability in each season. Ingested foods and ruminal characteristics greatly varied by season. Rumen digesta mainly comprised of graminoids in summer, graminoids and agricultural products in autumn, and bark and twigs in winter. Rumen pH showed seasonal differences ( P < 0.05) and was lowest in summer, highest in winter, and intermediate in autumn, reflecting the seasonal differences in ruminal concentration of total volatile fatty acids which were significantly lower ( P < 0.05) in winter than in summer and autumn. Acetate proportions were significantly higher in winter than in other seasons ( P < 0.05), while the opposite trend was seen in proportions of propionate and butyrate. Rumen ammonia levels showed significant seasonal differences ( P < 0.05), decreasing from summer to autumn to winter. Rumen protozoa levels in autumn and winter decreased to 28 and 10% of the levels observed in summer, respectively ( P < 0.05 for both). The rumen bacteria level in winter was lower ( P < 0.05) than that in autumn, but no difference was seen for the other seasonal comparisons. Gram negative cocci were present in significantly higher proportions in winter than in other seasons ( P < 0.05), while Gram negative curved rods were less frequently observed in winter ( P < 0.05). Based on these results, wild sika deer in this area are shown to survive with rumen microbial populations altered with the dietary conditions that vary greatly by season.

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1 Two types of Ca 2+ channel a 1 -subunits were co-expressed in Xenopus oocytes with the Ca 2+ channel a 2 -and b 1 -subunits. The Ba 2+ current through the a 1C a 2 b and the a 1B a 2 b channels had electrophysiological and pharmacological properties of L-and N-type Ca 2+ channels, respectively. 2 Amlodipine had a strong blocking action on both the L-type and N-type Ca 2+ channels expressed in the oocyte. The potency of the amlodipine block on the N-type Ca 2+ channel was comparable to that on the L-type Ca 2+ channel. At 7100 mV holding potential, the IC 50 values for amlodipine block on the L-type and N-type Ca 2+ channel were 2.4 and 5.8 mM, respectively. 3 The blocking action of amlodipine on the N-type Ca 2+ channel was dependent on holding potential and extracellular pH, as has been observed with amlodipine block on the L-type Ca 2+ channel. A depolarized holding potential and high pH enhanced the blocking action of amlodipine, 4 The time course of block development by amlodipine was similar for L-type and N-type Ca 2+ channels. However, it was slower than the time course of block development by nifedipine for the L-type Ca 2+ channel.