Glomerular hyperfiltration with hyperglycemia in the spontaneously diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model.

Glomerular hyperfiltration is observed in an early stage of kidney diseases including diabetic nephropathy. A better understanding of pathophysiological changes in glomerular hyperfiltration is essential for development of new therapies to prevent kidney disease progression. In this study, we investigated glomerular changes including glomerular filtration rate (GFR) and glomerular size in the Spontaneously Diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model, and we also evaluated pharmacological effects of the sodium glucose cotransporter 2 inhibitor dapagliflozin on the renal lesions. Dapagliflozin was administered to SDT fatty rats from 5 to 17 weeks of age. Blood and urinary biochemical parameters were periodically measured. GFR was determined by transdermal GFR monitor at 16 weeks of age and histopathological analysis was performed at 17 weeks of age. SDT fatty rat developed severe hyperglycemia and exhibited pathophysiological abnormalities in the kidney, such as an increased GFR, glomerular hypertrophy and tissue lesions. Dapagliflozin achieved good glycemic control during the experimental period, inhibited the increase in GFR, and improved histopathological abnormalities in tubules. These results suggest that the SDT fatty rat is a useful model for analyzing the pathogenesis of diabetic nephropathy during its early stage and dapagliflozin improves not only hyperglycemia but also glomerular hyperfiltration and tubule lesions in SDT fatty rat.

[Completion pneumonectomy for pulmonary aspergillosis with hyper immunoglobulin-E syndrome].

A 22-year-old man was admitted to the department of pediatrics of our institute in February 2005, because of pulmonary aspergillosis. He had been diagnosed as hyper immunoglobulin-E syndrome in infancy, and repeated pulmonary infectious desease, such as pulmonary aspergillosis. He received art of right upper lobectomy by pulmonary aspergillosis at the age of 17. In February 2005, he had hemosputum and the chest X-ray showed a giant cavity with niveau in the right lung. In spite of medical treatment by antibiotics and antimycotics, the lesion rapidly increased in size. Therefore, right completion pneumonectomy and omentopexy around the bronchial stump was done. His postoperative course was uneventful.

Hyponatremia and syndrome of inappropriate antidiuretic hormone secretion complicating stem cell transplantation.

Hyponatremia is a common electrolyte disorder in hospitalized patients. Although there are a few case reports of hyponatremia following stem cell transplantation (SCT), no reports concerning the incidence are currently available. We describe the occurrence of hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) following SCT. In a single center analysis of 140 patients, hyponatremia and SIADH were observed in 40 and 11.4% of patients, respectively, following SCT. Risk factors for SIADH included young age, transplantation from an HLA-mismatched or unrelated donor, cord blood transplantation, and graft-versus-host disease prophylaxis with methyl prednisolone. Multivariate analysis revealed that transplantation from an HLA-mismatched donor and performance of SCT in a child below 4 years of age were risk factors for SIADH. For patients who underwent SCT from an HLA-mismatched or unrelated donor, those with SIADH showed a significantly higher overall survival rate (90.9 vs 40.2%) and event-free survival rate (77.8 vs 33.8%) compared to those without SIADH. Overall, our data show that hyponatremia and SIADH are relatively common complications following SCT, especially in children below 4 years of age and after SCT from an HLA-mismatched donor.

Age-dependent expression of abdominal symptoms in patients with Yersinia enterocolitica infection.

BACKGROUND: The aim of the present study was to determine the relationship between the expression of abdominal symptoms and the age of patients with Yersinia enterocolitica infections. METHODS: Twenty-four patients with positive fecal cultures of Yersinia enterocolitica participated in the present study. The abdominal symptoms were taken from medical records. Statistical analysis was performed by Mann-Whitney U-test. RESULTS: Patients with diarrhea were younger than those without diarrhea (P = 0.014). Older children had abdominal pain or irritability more frequently than younger children (P = 0.004). CONCLUSIONS: In Yersinia enterocolitica infections, younger children are predisposed to diarrhea and older children are predisposed to abdominal pain.

Characterization of cytokine expression in the rectal mucosa of ulcerative colitis: correlation with disease activity.

OBJECTIVE: Mucosal inflammation in ulcerative colitis (UC) is presumed to be regulated by Th2-like cytokines. The aim of this study was to characterize local expression of various cytokines mRNA. METHODS: Total RNA was extracted from rectal biopsy specimens in 61 patients with UC, 18 inflammatory controls, and 16 noninflammatory controls. Reverse-transcription polymerase chain reaction (RT-PCR) was used to determine mRNA expression of interleukin (IL)-2, interferon (IFN)-gamma, IL-4, IL-10, IL-13, and IL-15. RESULTS: Expression of IL-10 was more frequent in UC (75.4%) than in noninflammatory controls (37.5%, p < 0.01). IL-4 was more frequently positive in UC (41%) than in inflammatory controls (5.6%, p < 0.01) and in noninflammatory controls (6.3%, p < 0.01). Positive expressions of IL-4 (66.7% vs 20.6%, p < 0.01) and IL-13 (63.0% vs 29.4%, p < 0.01) were higher in active UC than in inactive UC. The positive rate of IL-2, interferon (IFN)-gamma, and IL-15 expression showed no difference among the groups divided by clinical, endoscopic, and histological grade of inflammation. CONCLUSIONS: These findings suggest that in active UC, IL-4 is pivotal, in combination with other Th2-like cytokines. In contrast, Th1-like cytokines and IL-15 bear no definite relation to local inflammation of UC.

Protective effect of lactosucrose on intracolonic indomethacin-induced small-intestinal ulcers in rats.

BACKGROUND: Little is known about the role of intestinal microflora in the development of indomethacin-induced enteropathy. The aim of this study was to evaluate the effects of lactosucrose, an indigestible oligosaccharide, on intestinal microflora and on indomethacin-induced enteropathy in rats. METHODS: Male Wistar rats were fed either sucrose (SC) or lactosucrose (LS) for 2 weeks. Indomethacin (24 mg/kg/ day) was administered into the colon twice, 24 h apart, and intestinal ulcers in SC and LS groups were compared macroscopically. In another experiment the bacterial composition in the mid-small-intestinal segment was determined in both groups before and after treatment with indomethacin. RESULTS: After indomethacin treatment small-intestinal ulcers were less severe in the LS than in the SC group (ulcer index: median, 0.13 (range, 0.05-0.19) versus 0.23 (0.13-0.34); P < 0.05). Total bacterial count did not differ significantly between the two groups. Indomethacin increased the number of Enterobacteriaceae in both groups, but the increase was less in the LS group. The number of streptococci was also significantly increased in the SC group but not in the LS group. CONCLUSION: These results suggest that LS has some protective effects on indomethacin-induced enteropathy and that this protective effect is in part due to the maintenance of intestinal microflora.

Application of magnifying chromoscopy for the assessment of severity in patients with mild to moderate ulcerative colitis.

BACKGROUND: A magnifying colonoscope that enables high-power observation of the colorectal mucosa has been recently developed. The aim of this study was to investigate the value of the magnifying instrument in determining the severity of ulcerative colitis. METHODS: Magnifying colonoscopy was performed in 41 patients with ulcerative colitis, and the findings in the rectum were graded according to network pattern and cryptal openings. These findings were correlated with endoscopic, clinical, and histologic severity of the disease. RESULTS: Magnifying colonoscopy did not detect network pattern in 37% and cryptal opening in 24% of the subjects. The clinical, endoscopic, and histologic grades of activity were not different between groups divided by the presence or absence of each finding. However, when the two features were coupled, patients with visible network pattern and cryptal opening had a lower clinical activity index and lower grade of histologic inflammation than those in whom both findings could not be visualized. CONCLUSIONS: Observation under magnifying colonoscopy can be another clue to determining the severity of disease in patients with ulcerative colitis.

A case of systemic malignant lymphoma with intestinal involvement of lymphomatous polyposis type.

Multiple lymphomatous polyposis is a rare type of intestinal lymphoma characterized by non-Hodgkin's lymphoma of follicular mantle cell origin and extremely poor prognosis. We report a case of systemic lymphoma with the intestinal involvement of multiple lymphomatous polyposis. Although radiographic and endoscopic features of the case were compatible with multiple lymphomatous polyposis, histologic evidence suggested the diagnosis of diffuse large cell lymphoma rather than mantle cell lymphoma. Our case seems to be unique in its histologic findings and also in its prognosis, because the patient has been alive for more than 50 months after diagnosis.

Serum n3 polyunsaturated fatty acids are depleted in Crohn's disease.

To determine fatty acid patterns in Crohn's disease, we measured various serum fatty acids by gas chromatography in 20 patients with the disease and compared them with those in 18 healthy controls. All the patients had been free from any nutritional supplementation during preceding six months or had no history of intestinal resection. Eight of the patients were affected in the small bowel only, three in the large bowel only, and the remaining nine in both the small and large bowel. Both serum concentrations and percentages of C20:4n6, C20:5n3, C22:0, C22:6n3, total n3 polyunsaturated fatty acids, and total polyunsaturated fatty acids were lower in the patients than in the controls. Both essential fatty acids (C18:2n6, C18:3n3) and C20:3n9 levels were not different between the two groups. Among nine fatty acids that correlated with the Crohn's disease activity index, C20:5n3 and total n3 polyunsaturated fatty acids showed the most significant negative correlations. These findings suggest that essential fatty acid deficiency rarely occurs in Crohn's disease and also that n3 polyunsaturated fatty acids may be relevant to the activity of the disease.

Dysplasia in ulcerative colitis: is radiography adequate for diagnosis?

PURPOSE: To determine to usefulness of barium enema examination in detecting dysplasia in patients with ulcerative colitis. MATERIALS AND METHODS: Radiographic findings of 22 areas of dysplasia in 10 patients (seven men, three women; aged 34-81 years at diagnosis) were reviewed. Serial changes in radiographic features of four areas of dysplasia in three patients were retrospectively investigated. RESULTS: Fourteen of 22 areas of dysplasia were shown on radiographs. Dysplasia in the rectum or sigmoid colon was depicted less frequently than that in other segments of the colon. Radiographic features were classified as obvious nodular protrusions (seven lesions), irregular mucosa (five lesions), or nodular protrusions with irregular mucosa (two lesions). Six of the seven areas of dysplasia shown as irregular mucosa were accompanied by minute spiculations in the margin of the colonic lumen. There was no correlation between radiologic features and histologic grade of dysplasia. CONCLUSION: Barium enema examination may be used as a complementary method of cancer surveillance with endoscopy. These methods show about two-thirds of lesions associated with dysplasia.

Effects of diet on experimentally induced intestinal ulcers in rats: morphology and tissue leukotrienes.

The effects of dietary pretreatment on longitudinal ulcers of the intestine induced by indomethacin given intracolonically were investigated in rats. The rats were pretreated with either standard diet or liquid meals. Intracolonic indomethacin (24 mg/kg/day) given for two days produced longitudinal ulcers and small scattered ulcers in the small intestine in the control rats that were receiving standard pelleted formula. Three days pretreatment with one of two types of liquid meals, low residual diet (LRD) or elemental diet (ED), significantly reduced the incidence (3% in ED group and 0% in the LRD group) and the length of the longitudinal ulcers in the small intestine. The caecum was affected in each dietary pretreatment group (67% in controls, 80% in LRD group, and 69% in ED group). Colonic ulcers that were located in a longitudinal fashion were found in 42% of LRD group, while these ulcers were less frequently found in the ED group (13%) and controls (0%). Development of ulcers in the caecum and in the colon of rats in ED and LRD groups was more delayed than that of small intestinal ulcers of control rats. In another experiment, pretreatment by ED significantly increased colonic tissue leukotriene B4 concentration when compared with that of controls. These findings suggest that the site of experimental enteropathy induced by indomethacin given intracolonically can be modified by dietary pretreatment. This animal model can be available for investigating differences in the pathophysiology of enteropathy according to the site of involvement.

Is vitamin E depleted in Crohn's disease at initial diagnosis?

We measured serum and red blood cell concentrations of vitamin E and serum lipid concentrations in 13 inpatients at the initial diagnosis of Crohn's disease and compared them with those of 12 healthy controls. Although the serum concentrations of vitamin E were significantly lower in the patients with Crohn's disease than in the controls, the red blood cell concentrations of this vitamin did not differ between the two groups. The serum concentrations of total lipids and total cholesterol were decreased in the patients with Crohn's disease. A significant correlation was found between the red blood cell concentration of vitamin E and the serum vitamin E/serum total lipids ratio in both the groups. There was no correlation between the Crohn's disease activity index and serum or red blood cell levels of vitamin E. These findings suggest that the lowered serum vitamin E levels in patients with Crohn's disease are a symptom of hypolipidemia, and that vitamin E deficiency may not actually become a serious problem in patients diagnosed with Crohn's disease.

Preventive effect of immunosuppressive agents against indomethacin-induced small intestinal ulcers in rats.

The mechanism of nonsteroidal antiinflammatory drug-induced intestinal ulcers is not clearly understood. To evaluate whether immunosuppressants have a preventive effect against indomethacin-induced gastrointestinal damage, we investigated the effects of prednisolone, cyclosporin, and the newly developed immunosuppressant FK-506 in intracolonically indomethacin-treated rats: 24 mg/kg of indomethacin, administered intracolonically for two days, caused gastric ulcers and two types of small intestinal ulcers (longitudinal ulcers and scattered small ulcers). Pretreatment with intraperitoneal immunosuppressants reduced the size of gastric ulcers. Both cyclosporin (10 mg/kg) and FK-506 (1 mg/kg, 2 mg/kg) treatments significantly reduced the incidence and the length of the longitudinal ulcers of the small intestine when compared to the vehicle-treated controls, whereas prednisolone (20 mg/kg) did not show any preventive effect. Furthermore, the number of small scattered ulcers of the small intestine was significantly reduced by the high dose of FK-506 (2 mg/kg), but not by cyclosporin or prednisolone. These findings indicate that immunosuppressants have protective and antiinflammatory effects in indomethacin-induced gastroenteropathy, suggesting that cytokines may be important mediators in the pathogenesis of enteropathy induced by nonsteroidal antiinflammatory drugs.

Crohn disease: early recognition and progress of aphthous lesions.

PURPOSE: To clarify the radiographic appearance of the initial change an dprogression in Crohn disease. MATERIALS AND METHODS: Between 1984 and 1992, nine patients (seven men and two women, aged 16-34 years; mean, 20 years) with Crohn disease, who had evidence of only aphthous erosions or ulcers at the initial examination, underwent repeated radiography for up to 7 years 11 months (median, 4 years). RESULTS: In all patients, the stomach, duodenum, small intestine, and colorectum were involved, and the esophagus was affected in three patients. Subsequently, four of the nine patients had lesions that progressed from aphthous lesions to overt Crohn disease, including ileitis in two patients, colitis in one, and ileocolitis in one. Time intervals between the first visit and the progression varied from 9 months to 3 years 6 months. In all eight patients who underwent nutritional treatment, regression of the lesions was recognized, but three of the lesions progressed during interruption of the nutritional diet. CONCLUSION: Crohn disease may initially appear as diffuse aphthous lesions in the gastrointestinal mucosa.