Changes in sodium transport in epithelial cells in a rat ileal-augmented bladder model

OBJECTIVE: To investigate changes in the morphology and sodium transport ability of intestinal epithelium diverted to the urinary tract, using an in vitro sodium-binding benzofuran isophthalate (SBFI) technique, as the effects of long-term urine exposure on the transport of electrolytes through intestine are incompletely understood. MATERIALS AND METHODS: Ileal augmentation cystoplasty was conducted in female Sprague-Dawley rats; at 3 and 12 months after surgery the serum concentration of sodium, chloride and potassium were measured. Sodium transport in the ileal epithelial cells diverted to the urinary tract was evaluated using SBFI, as the value of the 340/380 nm excitation ratio measured with fluorescence spectrophotometry. The villous height and the number of villi per ileal length were obtained from haematoxylin and eosin-stained sections. RESULTS: After 3 months the mean (sd) serum sodium concentrations in normal and augmented rats were 140.4 (2.5) and 140.7 (3.5) mmol/L, respectively; the chloride concentration in normal rats was 97.0 (2.9), and in augmented rats at 3 and 12 months it was 102.4 (2.9) and 99.0 (3.7) mmol/L, respectively. At 3 months, chloride concentrations were significantly higher in augmented than in normal rats (P < 0.05). The mean (sd) 340/380 nm ratio increased by 0.85 (0.09) in the normal ileum, and by 0.73 (0.15) and 0.49 (0.23) in the ileum of augmented rats at 3 and 12 months, respectively; the difference between normal and augmented ileum at 12 months was significant (P < 0.05). At 12 months the villous height in the augmented ileum, at 227.6 (16.0) micro m, was significantly less than in the normal ileum, at 803.4 (66.2) micro m (P < 0.05). However, the number of villi/mm ileum in normal and augmented rats at 12 months was 13.7 (1.5) and 15.0 (0.8), respectively, and not significantly different. CONCLUSION: Sodium transport decreased significantly after long-term exposure to urine; the improvement in metabolic change was probably attributable to alterations of electrolyte transport and atrophic changes of the villus.     

Stage-dependent changes in trabecular bone turnover and osteogenic capacity of marrow cells during development of type II collagen-induced arthritis in mice

Rheumatoid arthritis (RA) is a disease characterized by inflammatory polyarthritis leading to destruction of the joints and reduction in bone mass. However, the relationship between bone mass and turnover is not yet clear in RA patients. To clarify the effect of bone turnover and marrow osteogenic capacity on mass and structure during the development of arthritis, we examined DBA1/J mice for 8 weeks after the first immunization with bovine type II collagen at the age of 9 weeks. Localized arthritis developed at 4 weeks and advanced arthritis at 6 weeks postimmunization. Urinary deoxypyridinoline levels in arthritic mice were significantly higher at 4 weeks, and levels were maintained thereafter. Their serum osteocalcin levels were significantly reduced compared with controls at 2 and 6 weeks, but did not differ significantly from those in the control group at 4 and 8 weeks. Three-dimensional (3D) trabecular bone volume of the proximal tibia measured by 3D microcomputed tomography (micro-CT) in the arthritic mice became significantly lower at 4 weeks and decreased further at 6 weeks compared with controls. Parameters of 3D trabecular bone structure, such as structure model index and trabecular bone pattern factor, were increased at 4 and 6 weeks, respectively. Trabecular osteoclast number increased and bone formation rates decreased at 8 weeks. The number of total bone marrow cells (BMCs), adherent stromal cells, and area of mineralized nodule formation in the tibia of arthritic mice were significantly reduced compared with controls at 6 weeks. Numbers of total fibroblastic colony-forming units (CFU-f) and alkaline phosphatase (ALP)-positive CFU-f colonies also decreased. However, the values of these osteogenic parameters corrected for the total BMCs and/or adherent stromal cells did not differ significantly between the arthritic and control groups. These data indicate that an increase in bone resorption led to the reduction in trabecular bone mass and deterioration of 3D structure during the localized arthritic stage. The reduction in bone marrow osteogenic potential in the advanced arthritic stage was due to the reduction in the number of total bone marrow cells, and differentiation of osteogenic cells was apparently unaffected. The reduction in bone formation may not be substantial in this arthritic model.     

Expression of HLA-DR and its enhancing molecules in muscle fibers in polymyositis

Polymyositis (PM) is an autoimmune inflammatory muscle disease of unknown cause in which cellular immunity is thought to play an important pathogenic role. Class II major histocompatibility complex (class II MHC: human leukocyte antigen (HLA)-DR operates as a cofactor of antigen presentation in immunological responses. There has been a major debate over whether muscle fibers themselves synthesize and express HLA-DR molecules and play a role in antigen presentation in PM pathogenesis. In this study, we demonstrated that most muscle fibers from patients with PM synthesized and expressed HLA-DR molecules on their surface. Human leukocyte antigen-DR expression was highly specific to PM. In addition, class II transactivator (CIITA), human leukocyte antigen DM (HLA-DM), and invariant chain (Ii), which are indispensable for expression of mature HLA-DR molecules and for antigen processing and presentation, were co-expressed. One of the cytokines that could induce this expression is interferon-gamma (IFN-gamma), released by activated lymphocytes. Our results indicate that in PM muscle fibers synthesize and express HLA-DR molecules and may contribute to the inflammatory responses together with lymphocytes.     

Alcoholic liver diseases and hepatitis virus C in Japan]

Recently incidence of alcoholic liver disease (ALD) has been increasing in Japan associated with an increase in alcoholic beverage consumption. There have been a large number of reports about the relationship between alcohol and hepatocarcinogenesis, but it remains controversial. In the present study, we addressed the recent trend in incidence of ALD including liver cirrhosis (LC), and hepatocellular carcinoma (HCC) in heavy drinkers in Japan. We carried out nation-wide survey by asking for the hospitals that are approved by the Japanese Society of Gastroenterology for recent aspects of in-patients with ALD. Except for HCC, percentage of ALD without viral hepatitis is more than 70%, which is increased when compared to the national survey carried out in 1992. In alcoholic LC patients, those who did not have viral hepatitis were 81%. However, the percentage of HCC without viral hepatitis was 34% of all of the heavy drinkers with HCC. Regarding the case in our university hospital, 138 cases (32%) of 432 patients with HCC were heavy drinkers. However, regarding in our general hospital, 15 cases of 23 patients with HCC (61%) were heavy drinkers. In conclusion, since the consumption of alcohol is increasing in Japan, the frequency and number of cases of alcoholic liver cirrhosis are increasing. Viral hepatitis infection, however, still plays an important role in hepatocarcinogenesis in heavy drinkers.     

Peroxisome proliferator-activated receptor δ (PPARδ), a novel target site for drug discovery in metabolic syndrome

The development of new treatments for metabolic syndrome is urgent project for decreasing the prevalence of coronary heart disease and diabetes mellitus in the advanced countries. Peroxisome proliferator-activated receptor (PPAR)α and γ agonists have shed light on the treatment of hypertriglyceridemia and type 2 diabetes mellitus, respectively. Among PPARs, analysis of the PPARδ functions is lagging behind because specific PPARδ agonists have not been developed. The appearance of new PPARδ agonists is brightening the prospects for elucidating the physiological role of PPARδ. PPARδ is a new target for the treatment of metabolic syndrome. In particular, the fact that fatty acid oxidation and energy dissipation in skeletal muscle and adipose tissue by PPARδ agonists lead to improved lipid profile, reduced adiposity and insulin sensitivity is a breakthrough. It seems that treatment of PPARδ agonists operate similarly to the caloric restriction and prolonged exercise. We suggest that the physiological role of PPARδ may be an indicator for switching from glucose metabolism to fatty acid metabolism. To receive new benefits of PPARδ agonists against metabolic syndrome by increasing fatty acid consumption in skeletal muscle and adipose tissue, we need to unveil more details on the functions of PPARδ itself and its agonists in the future.     

Chronic social stress reduces dendritic arbors in CA3 of hippocampus and decreases binding to serotonin transporter sites

Male rats housed in mixed-sex groups in a visible burrow system (VBS) form a dominance hierarchy in which subordinate animals show stress-related changes in behavior, endocrine function and neurochemistry. Dominants also appear to be moderately stressed compared to controls, although these animals do not develop the more pronounced behavioral and physiological deficits seen in the subordinates. In the present study, we examined the effects of chronic psychosocial stress on the morphology of Golgi-impregnated CA3 pyramidal neurons. In addition, since serotonin has been implicated in the mechanisms mediating the dendritic remodeling seen with other chronic stress regimens, we used quantitative autoradiography to measure binding to the serotonin transporter (5HTT) in hippocampus and dorsal and median raphe. Chronic social stress led to a decrease in the number of branch points and total dendritic length in the apical dendritic trees of CA3 pyramidal neurons in dominant animals compared to unstressed controls; subordinates also had a decreased number of dendritic branch points. [(3)H]paroxetine binding to the 5HTT was decreased in Ammon's horn in both dominants and subordinates compared to controls, while 5HTT binding remained unchanged in dentate gyrus and raphe. The similarity of the changes in 5HTT binding and dendritic arborization between both groups of VBS animals, despite apparent differences in stressor severity, suggests that these changes may be part of the normal adaptive response to chronic social stress. The mechanisms underlying dendritic remodeling in CA3 pyramidal neurons are likely to involve stress-induced changes in glucocorticoids and in 5HT and other transmitters.     

Serum heat shock protein 70 levels and lung cancer risk: a case-control study nested in a large cohort study.

Chronic inflammation contributes to the process of carcinogenesis, but few epidemiologic studies have examined associations with risk of lung cancer. Relationships between lung cancer risk and serum levels of both heat shock protein 70 (Hsp70) and high-sensitivity C-reactive protein (hsCRP) were investigated in a case-control study nested in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. Serum samples and lifestyle information were collected at baseline from 39,242 men and women between 1988 and 1990. Of these, 240 deaths from lung cancer were identified through 1999, and 569 controls were matched for sex, age, and study area. Serum levels were measured in 189 cases and 377 controls for Hsp70 and in 209 cases and 425 controls for hsCRP. Odds ratios (95% confidence intervals) across quartiles, adjusted for confounding factors, including smoking habits, were 0.83 (0.44-1.58), 1.41 (0.77-2.60), and 1.84 (0.92-3.71) for Hsp70 (P(trend) = 0.042) and 1.13 (0.67-1.91), 0.66 (0.38-1.16), and 1.19 (0.70-2.02) for hsCRP (P(trend) = 0.941). In males, odds ratios (95% confidence intervals) across quartiles were 1.30 (0.59-2.84), 1.74 (0.83-3.67), and 2.49 (1.06-5.85) for Hsp70 (P(trend) = 0.029). High levels of serum Hsp70 might thus be associated with increased risk of lung cancer among Japanese males, although further studies are needed to clarify associations between chronic inflammation and lung cancer.     

Key factors influencing bowel function after ileal W-pouch anal anastomosis: A spectral analysis of W-pouch motor activity

Restorative proctocolectomy with ileal pouch anal anastomosis (IPAA) has become the standard surgical procedure for ulcerative colitis (UC). The purpose of this study was to determine which factors are important to achieve good anal continence after IPAA in terms of the motor activity and pressure–volume relationship. A total of 17 patients with UC who underwent IPAA were evaluated. The internal ileal pouch pressure was transanally measured with and without volume-loading of the pouch which induces the urge to evacuate. The maximum tolerable volume (MTV), first urge volume (FUV), and ileal pouch compliance were calculated and the internal ileal pouch pressure records were subjected to spectral analysis for intensive evaluation of the intraluminal pressure waves. The FUV, correlation of the compliance of the FUV with MTV, and the remaining volume up to the MTV (RVMTV) were analyzed. Compliance of the FUV was significantly correlated with the RVMTV (r = 0.736, P < 0.01). The frequency of the phasic waves in the pouch decreased with length of follow up, reflecting improved function (r = −0.588, P < 0.05). The findings of this intensive analysis of manometric measurement indicate that the key factors in postoperative pouch function are RVMTV and the frequency of phasic waves in the W-pouch. Received: May 6, 1999 / Accepted: May 30, 2000