Topographical anatomy of Spiegel's lobe and its adjacent organs in mid‐term fetuses: Its implication on the development of the lesser sac and adult morphology of the upper abdomen

At 8–16 weeks of gestation, Spiegel's lobe of the caudate lobe appears as a sac‐like herniation of the liver parenchyma between the inferior vena cava and ductus venosus or Arantius' duct. In 5 of 11 fetuses at 20–30 weeks of gestation, we found that an external notch was formed into the posterior aspect of the caudate lobe by a peritoneal fold containing the left gastric artery. This notch appeared to correspond to that observed in adults, which is usually seen at the antero‐inferior margin of the lobe after rotation of the lobe along the horizontal or transverse axis. However, the notch did not accompany two of the three fetuses in which the left hepatic artery originated from the left gastric artery. Notably, until 9–10 weeks of gestation, the inferior and left part of Spiegel's lobe rode over the hepatoduodenal ligament and protruded medially into the lesser sac (bursa omentalis) behind the stomach. Thus, the fetal Winslow's foramen was located at the “superior” side of the ligament. However, as seen in adults, the protruding Spiegel's lobe was located at the posterior side of the lesser omentum. Therefore, a hypothetical rotation along the transverse axis in the later stages of development seems necessary to explain this repositioning. Considering that Spiegel's lobe develops faster than surrounding structures, it is likely that the lesser sac resulting from the rotation of the gastrointestinal tract, which actively contributes to facilitate the growth of the Spiegel lobe. Clin. Anat. 23:712–719, 2010. © 2010 Wiley‐Liss, Inc.     

Computational modeling of dendritic tiling by diffusible extracellular suppressor

The development of neuronal class‐specific dendrites is a basis for the correct functioning of the nervous system. For instance, tiling of dendritic arbors (complete, but minimum‐overlapping innervation of a field) supports uniform reception of input stimuli. Previous studies have attempted to show the molecular and cellular basis of tiling, and it has been argued that the underlying inhibitory interaction between dendrites is realized by contact‐dependent retraction and/or by repulsion of dendrites via extracellular branch suppressors. In this study, we showed that the development and regeneration of the tiling pattern could be reproduced by two different mathematical models (the cell compartment model and the end capped‐segment model), in both of which dendrite growth is coupled with the dynamics of an extracellular suppressor that is secreted from dendrites. The analysis of the end capped‐segment model in three‐dimensional space showed that it generated both non‐overlapping arbors as well as overlapping dendritic arbors, which patterns are reminiscent of phenotypes of previously reported tiling mutants in vivo. Moreover, the results of our numerical analysis of the 2 models suggest that tiling patterns could be achieved either by a local increase in the concentration of an intracellular branching activator or by a local decrease in the production of a suppressor at branch ends.     

Factor analysis of lifestyle-related factors in 12,525 urban Japanese subjects

This study describes the clustering patterns of several lifestyle-related factors in urban Japanese subjects. The effect of aging on these patterns was also investigated. Data of 8 factors that included body mass index (BMI), blood pressure (BP), fasting plasma glucose (FPG), serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLc), gamma-glutamyl-transferase (GGT), and cigarette smoking were analyzed for 12,525 individuals (4,591 men and 7,934 women) aged either 40, 50, or 60 years. Factor analysis showed eight factors clustered into 3 unrelated groups. BMI and BP were excluded in subjects aged 60 years. Our data showed that the effect of obesity on the prevalence of type 2 diabetes mellitus was age dependent. In spite of the established inverse relationship between TG and HDLc, we found that TG had an association with GGT. These results indicated that aging may have a major influence on the expression of multiple risk factors. The influence of BMI on the lifestyle-related factors appeared to be mostly expressed in younger people, while these factors appeared to be independent of BMI at age 60.     

Thalidomide ameliorates carbon tetrachloride induced cirrhosis in the rat

OBJECTIVE: Thalidomide has anti-inflammatory, anti-tumour necrosis factor-alpha and anti-collagen activities. Cirrhosis is characterized by inflammation and fibrosis. Thus, thalidomide was evaluated in an experimental model of liver cirrhosis. METHODS: Male Wistar rats were used. Group 1 (n = 8) received mineral oil i.p. (control); group 2 (n = 15) received CCl(4) i.p. for 8 weeks to induce cirrhosis; group 3 (n = 15) consisted of rats receiving CCl(4) plus thalidomide (200 mg/kg/12 h); animals in group 4 (n = 8) received thalidomide only. Alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (gamma-GTP) and alkaline phosphatase (ALP) were measured in serum, while collagen (hydroxyproline), glycogen and lipid peroxidation were determined in liver samples. A liver histopathological analysis was performed by using Gomori's trichromic staining. RESULTS: Intoxication with CCl(4) induced 33.3% mortality, while thalidomide co-treatment reduced it to 13.3%. The serum activities of ALT, gamma-GTP and ALP increased 3, 2 and 4-fold by CCl(4) treatment; thalidomide completely prevented elevation of these enzymes. In the liver, lipid peroxidation increased about 20-fold and glycogen was abolished in CCl(4) cirrhotic rats; thalidomide completely prevented the former and partially (P < 0.05) the latter. CCl(4) treated rats revealed a loss of normal architecture and nodules of hepatocytes surrounded by thick bands of collagen. Thalidomide + CCl(4) treated rats showed minor histological alterations and thinner bands of collagen. The anti-fibrotic effect estimated by hydroxyproline was partial but significant (P < 0.05). CONCLUSION: Thalidomide prevented necrosis, cholestasis and fibrosis induced by CCl(4). Its mechanism of action may be related to its anti-inflammatory, anti-tumour necrosis factor-alpha and anti-fibrotic activities reported previously.     

Physiological and pathological age-associated changes in diurnal rhythm of energy expenditure in rats

Although the idea that energy metabolism of rats decreases with age has been widely accepted, few studies with regard to the diurnal rhythm of energy expenditure have been reported. Whether age alone altered the diurnal rhythm of energy expenditure was examined in Sprague-Dawley (SD) rats. The same determination was conducted in Otsuka Long Evans Tokushima Fatty (OLETF) rats to examine the effect of insulin resistance and diabetes. OLETF rats were developed as a model of non-insulin-dependent diabetes mellitus (NIDDM) with mild obesity. The characteristic features of OLETF rats are late onset of hyperglycemia at about 18 weeks of age, followed by insulin deficiency at about 65 weeks. Age-associated changes in diurnal rhythm of energy expenditure were not observed in SD rats. In OLETF rats, the diurnal rhythm of energy expenditure with two peaks was observed at 8 weeks of age, while these two peaks disappeared at 24 weeks of age (with NIDDM). Then, the pattern of diurnal rhythm at 44 weeks of age (with advanced NIDDM) was resembled to that of 62 weeks of age (with insulin deficiency). In conclusion, we clarified the changes in diurnal rhythm of energy expenditure associated with the progress of diabetes, while age alone did not alter the diurnal rhythm.     

Different effects of ghrelin, des-acyl ghrelin and obestatin on gastroduodenal motility in conscious rats

Three peptides, ghrelin, des-acyl ghrelin and obestatin are derived from a common prohormone, preproghrelin by posttranslational processing, originating from endocrine cells in the stomach. To examine the effects of these peptides, we applied the manometric mea- surement of gastrointestinal motility in freely moving conscious rat models. Ghrelin exerts stimulatory ef- fects on the motility of antrum and duodenum in both fed and fasted state of animals. Des-acyl ghrelin exerts inhibitory effects on the motility of antrum, but not on the motility of duodenum in the fasted state of ani- mals. Obestatin exerts inhibitory effects on the motility of antrum and duodenum in the fed state, but not in the fasted state of animals. NPY Y2 or Y4 receptors in the brain may mediate the action of ghrelin, CRF type 2 receptors in the brain mediate the action of des-acyl ghrelin, whereas CRF type 1 and type 2 receptors in the brain mediate the action of obestatin. Vagal afferent pathways might be involved in the action of ghre- lin, but not involved in the action of des-acyl ghrelin, whereas vagal afferent pathways might be partially involved in the action of obestatin.     

Ghrelin family of peptides and gut motility

Acyl ghrelin, des-acyl ghrelin, and obestatin are three peptides isolated from the gastrointestinal tract and encoded by the same preproghrelin gene. Three ghrelin gene products participate in modulating appetite, adipogenesis, glucose metabolism, cell proliferation, immune, sleep, memory, anxiety, cognition, and stress. We have investigated the effects of ghrelin family of peptides on fed and fasted motor activities in the stomach and duodenum of freely moving conscious rats by manometric method. Intracerebroventricular (ICV) and intravenous (IV) administration of acyl ghrelin induced fasted motor activity in the duodenum in fed rats. ICV and IV administration of des-acyl ghrelin disrupted fasted motor activity in the antrum. Changes in gastric motility induced by IV administration of des-acyl ghrelin were antagonized by ICV administration of a corticotropin-releasing factor (CRF) 2 receptor antagonist. IV administration of obestatin decreased the percentage motor index in the antrum and prolonged the time taken to return to fasted motility in the duodenum in fed rats. ICV administration of CRF 1 and 2 receptor antagonists prevented the effects of obestatin on gastroduodenal motility. Ghrelin gene products regulate feeding-associated gastroduodenal motility. Stomach may regulate various functions including gastrointestinal motility via acyl ghrelin, des-acyl ghrelin and obestatin as an endocrine organ. Increasing knowledge of the effects of ghrelin family of peptides on gastrointestinal motility could lead to innovative new therapies for functional gastrointestinal disorders.