Angiotensin II(A II) -a main effector molecule of renin-angiotensin system(RAS) has been known to increase blood pressure and glomerular capillary pressure, and filtration fraction which may be involved in the progressive renal injury process. The action of A II takes place mainly through AT1 receptor. RAS can be blocked by angiotensin converting enzyme inhibitor(ACEI) and recently developed A II AT1 receptor antagonist(AT1 RA). ACEI also activate kinin system, simultaneously. However, AT1 RA does not affect kinin system. The renoprotective mechanism of ACEI may be related with activation of kinin system. In order to evaluate the renoprotective mechanism of long-term ACEI(enalapril, 100mg/L in drinking water for 12 weeks) or AT1 RA treatment(losartan 300mg/L in drinking water for 12 weeks), and its effect on the cytokines and growth factor expressions of renal cortical tissue by compatitive RT-PCR, 46 5/6 nephrectomized(5/6 NPX) rats and 8 sham operated rats were included in this study. Five sixth NPX rats showed marked hypertensin, significant proteinuria and glomerulosclerosis(mean 30.5%) in 12 weeks after surgery. However, enelapril or losartan treated rats revealed significantly lower 24 hour urinary protein excretion(UProtV), systolic blood pressure(SBP), and glomerulosclerosis than those of control 5/6 NPX rats. Plasma renin activity and angiotensin II levels of 5/6 NPX untreated control rats were not significantly increased compared to sham operated rats in 12 week after surgery. Renal cortical renin gene expression of untreated 5/6 NPX rats was significantly suppressed compared to sham operated rats. Enalapril or losartan treated 5/6 NPX rats showed significantly increased renin gene expression compared to untreated 5/6 NPX rats. Renal cortical gene expressions of TGF-beta, TNF-alpha, MCP-1, IL-6, osteopontin, and endothelin-1 were significantly increased in 5/6 NPX untreated control rats compared to sham operated rats. Enalapril or losartan treated 5/6 NPX rats showed significantly less level of renal TGF-beta gene expression compared to 5/6 NPX control rats. The magnitude of SBP and UProtV were significantly positively correlated with the degree of glomeruloslerosis(p<0.001, p<0.001). With the above result, we speculate that because ACEI or AT1 RA showed similar renoprotective effect in 5/6 NPX rats, at least in part, local activation of RAS plays an important role in the progressive renal injury process of this model.
Angiotensin Amide ; Angiotensin II ; Angiotensins ; Animals ; Blood Pressure ; Capillaries ; Cytokines ; Drinking Water ; Enalapril ; Endothelin-1 ; Filtration ; Gene Expression ; Interleukin-6 ; Losartan ; Osteopontin ; Peptidyl-Dipeptidase A ; Plasma ; Proteinuria ; Rats ; Renin ; Renin-Angiotensin System* ; Transforming Growth Factor beta ; Tumor Necrosis Factor-alpha

Angiotensin II(A II) -a main effector molecule of renin-angiotensin system(RAS) has been known to increase blood pressure and glomerular capillary pressure, and filtration fraction which may be involved in the progressive renal injury process. The action of A II takes place mainly through AT1 receptor. RAS can be blocked by angiotensin converting enzyme inhibitor(ACEI) and recently developed A II AT1 receptor antagonist(AT1 RA). ACEI also activate kinin system, simultaneously. However, AT1 RA does not affect kinin system. The renoprotective mechanism of ACEI may be related with activation of kinin system. In order to evaluate the renoprotective mechanism of long-term ACEI(enalapril, 100mg/L in drinking water for 12 weeks) or AT1 RA treatment(losartan 300mg/L in drinking water for 12 weeks), and its effect on the cytokines and growth factor expressions of renal cortical tissue by compatitive RT-PCR, 46 5/6 nephrectomized(5/6 NPX) rats and 8 sham operated rats were included in this study. Five sixth NPX rats showed marked hypertensin, significant proteinuria and glomerulosclerosis(mean 30.5%) in 12 weeks after surgery. However, enelapril or losartan treated rats revealed significantly lower 24 hour urinary protein excretion(UProtV), systolic blood pressure(SBP), and glomerulosclerosis than those of control 5/6 NPX rats. Plasma renin activity and angiotensin II levels of 5/6 NPX untreated control rats were not significantly increased compared to sham operated rats in 12 week after surgery. Renal cortical renin gene expression of untreated 5/6 NPX rats was significantly suppressed compared to sham operated rats. Enalapril or losartan treated 5/6 NPX rats showed significantly increased renin gene expression compared to untreated 5/6 NPX rats. Renal cortical gene expressions of TGF-beta, TNF-alpha, MCP-1, IL-6, osteopontin, and endothelin-1 were significantly increased in 5/6 NPX untreated control rats compared to sham operated rats. Enalapril or losartan treated 5/6 NPX rats showed significantly less level of renal TGF-beta gene expression compared to 5/6 NPX control rats. The magnitude of SBP and UProtV were significantly positively correlated with the degree of glomeruloslerosis(p<0.001, p<0.001). With the above result, we speculate that because ACEI or AT1 RA showed similar renoprotective effect in 5/6 NPX rats, at least in part, local activation of RAS plays an important role in the progressive renal injury process of this model.
Angiotensin Amide ; Angiotensin II ; Angiotensins ; Animals ; Blood Pressure ; Capillaries ; Cytokines ; Drinking Water ; Enalapril ; Endothelin-1 ; Filtration ; Gene Expression ; Interleukin-6 ; Losartan ; Osteopontin ; Peptidyl-Dipeptidase A ; Plasma ; Proteinuria ; Rats ; Renin ; Renin-Angiotensin System* ; Transforming Growth Factor beta ; Tumor Necrosis Factor-alpha

Sj gren's syndrome(SS) is a systemic autoimmune disorder characterized by lymphocytic infiltration of the lacrimal and salivary glands, which result in dry eye and dry mouth. Systemic involvement including the lungs, gastrointestinal tract, kidneys, endocrine glands, skin, or nervous system has been reported. Pulmonary abnormalities in SS are lymphoid interstitial infiltration, chronic bronchitis, pulmonary fibrosis and pleurisy. Pulmonary pseudolymphoma associated with acute renal insufficiency is very rare. Recently, we experienced a patient with SS presenting with a huge pulmonary mass in the left upper lobe and acute renal failure. Pulmonary pseudolymphoma and renal functional impairment were completely reversed after a six month treatment with oral prednisolon(1mg/kg, body weight) and monthly cyclophosphamide pulse therapy (12mg/kg, I.V.). There was no evidence of disease recurrence for 16 months after discontinuation of prednisolone therapy.
Acute Kidney Injury ; Bronchitis, Chronic ; Cyclophosphamide ; Endocrine Glands ; Gastrointestinal Tract ; Humans ; Kidney ; Lung ; Mouth ; Nervous System ; Pleurisy ; Prednisolone ; Pseudolymphoma ; Pulmonary Fibrosis ; Recurrence ; Salivary Glands ; Skin

In order to evaluate the renal expression of renin, TGF-beta, TNF-alpha, IL-6, MCP-1, endothelin-1, osteopontin, and the role of renin-angiotensin system(RAS) in renal injury mechanism of experimental unilateral ureteral obstruction(UUO), 44 male Sprague-Dawley rats weighing 260-280g underwent sham operation(n= 8), UUO without treatment(n=12), UUO with angiotensin converting enzyme inhibitor(ACEI, enalapril 100 mg/kg body weight in drinking water, n=12) and UUO with angiotensin II AT1 receptor antagonist(AT1 RA, losartan 300mg/Kg body weight in drinking water, n= 12) under thiopental sodium anesthesia(50mg/kg, body weight, I.P.). Half number of each group was sacrificed at 3 and 7 days after surgery. With standard point count method, we evaluated the magnitude of tubulointerstitial mononuclear cell infiltration and relative volume of interstitium by light microscopic examination (PAS stain and immunohistochemistry for ED-1). Competitive RT-PCR was performed for the estimation of renin, TGF-beta, TNF-alpha, IL-6, MCP-1, endothelin-1, osteopontin and beta-actin gene expression levels of the kidneys. Renal gene expressions of renin, TGF-beta, MCP-1, TNF-alpha, IL-6, endothelin-1, and osteopontin of untreated control UUO rats were significantly increased compared to sham operated rats at 3 and 7 days after surgery. The level of TGF-beta, TNF-alpha, IL-6 and endothelin-1 gene expressions of ACEI treated UUO rats was significantly lower than those of untreated control UUO rats. AT1 RA treated UUO rats also showed significantly lower level of TGF-beta and osteopontin gene expression than those of control UUO group. Untreated control UUO rats showed significantly increased mononuclear cell infiltration of tubulointerstitium and relative volume of interstitium of the kidney compared to sham operated rats. ACEI or AT1 RA treated UUO rats showed significantly less relative volume of interstitium and mononuclear cell infiltration than those of untreated UUO rats(p<0.05, p<0.05). With the above result, we speculate that the upregulation of renin, TGF-beta, MCP-1, TNF-alpha, IL-6, osteopontin and endothelin-1 genes is closely related to the progressive renal injury process in this model and at least in part, the early activation of renin angiotensin system of the kidney is involved in this mechanism.
Actins ; Angiotensin II ; Animals ; Body Weight ; Drinking Water ; Enalapril ; Endothelin-1 ; Gene Expression ; Humans ; Immunohistochemistry ; Interleukin-6 ; Kidney ; Losartan ; Male ; Osteopontin ; Peptidyl-Dipeptidase A ; Rats ; Rats, Sprague-Dawley ; Renin ; Renin-Angiotensin System* ; Thiopental ; Transforming Growth Factor beta ; Tumor Necrosis Factor-alpha ; Up-Regulation ; Ureter* ; Ureteral Obstruction*

Hepatoid adenocarcinoma is a rare variant of adenocarcinoma of the stomach. The tumor has been found to be an alpha-fetoprotein (AFP) producing carcinoma arising in extrahepatic organs, and it mimics hepatocellular carcinoma in terms of morphology and function. Vascular invasion, usually prominent, is often complicated by extensive liver metastases, and vascular permeation, especially in the veins, has been described as a characteristic finding of this tumor. A patient with hepatoid adenocarcinoma of the stomach with a huge mass is described. Gastrofiberscopy revealed an elevated lesion with a central depression on the greater curvature of the antrum and with extrinsic compression on the lesser curvature and the duodenum. Computed tomography revealed a large lobulated mass in the lesser curvature of the stomach, attached from the liver, gall bladder and porta hepatitis to the pancreas. The AFP serum level was markedly elevated. After a diagnosis was made of AFP-producing stomach carcinoma with huge lymph node metastasis, subtotal gastectomy with wedge resection of the liver, and cholecystectomy including the huge mass ware performed. Microscopically, the tumor and intraabdominal huge mass showed mainly hepatoid differentiation. The tumor showed immunohistochemical positivity for AFP and huge lesser omental metastasis with adhesion to the liver and extensive venous invasion. Lymph node metastasis was not found. According to these histopathological findings, the tumor was diagnosed as hepatoid adenocarcinoma of the stomach with venous invasion. We report this rare variant of adenocarcinoma of the stomach, which mimics hepatocellular carcinoma in its propensity for venous permeation.
Adenocarcinoma* ; alpha-Fetoproteins ; Carcinoma, Hepatocellular ; Cholecystectomy ; Depression ; Diagnosis ; Duodenum ; Hepatitis ; Humans ; Liver ; Lymph Nodes ; Neoplasm Metastasis ; Pancreas ; Stomach* ; Urinary Bladder ; Veins

BACKGROUND: Cardiopulmonary bypass(CPB) induces the productions of several inflammatory mediators that may be implicated in postoperative organ dysfunction, a problem to which the pediatric population is particularly prone. The purpose of this study was to determine if gene expressions of proinflammatory cytokines and chemokines were activated in plasma subjected to pediatric patients who underwent CPB for congenital heart diseases. MATERIAL AND METHOD: Blood was taken from the radial artery of eighteen pediatric patients after induction of anesthesia(baseline), immediately after CPB(0 hour), 2 hours, 24 hours, and 48 hours after CPB. The mRNA expressions of interleukin-1alpha (IL-1alpha ), Interleukin-1beta(IL-1beta), Interleukin-6 (IL-6), Interleukin-8(IL-8), Tumor necrosis factor-alpha (TNF-alpha ), Interleukin-15(IL-15), and Interferon-gamma(INF-gamma) were evaluated with semiquantitative reverse transcription-polymerase chain reaction(RT-PCR). IL-6 protein levels were measured in six patients by using enzyme-linked immunosorbent assay(ELISA.) RESULT: Systemic IL-6 mRNA and protein increased from baseline to a peak at 0 hour(239.5 pg/ml; p=0.01 versus baseline) and sustained at 2 hours before declining at 24 hours(82.7 pg/ml; p<0.05 versus 0hour). In IL-8 mRNA, there was a similar pattern but the increase was smaller than that of IL-6. IL-1 and IL-1 mRNA expressions peaked later(2 hours) from baseline, and declined by 48 hours. TNF- levels peaked at 24 hours, and declined by 48hours. There were no significant differences between before and after bypass were seen in IL-15 mRNA production. IFN- levels gradually decreased during the course of time. CONCLUSION: Gene expressions of IL-6, IL-8, IL-1alpha , IL-beta and TNF-alpha were changed significantly in plasma of pediatric patients who underwent CPB for congenital heart disease. IL-15 showed a different proinflammatory. response, and reverse responses were shown in IFN-gamma mRNA expression. These may result in high concentrations of proinflammatory cytokines and chemokines in the blood after CPB, contributing to the tissue injury.
Cardiopulmonary Bypass ; Chemokines* ; Cytokines* ; Gene Expression* ; Heart Defects, Congenital ; Heart Diseases ; Humans ; Interleukin-1 ; Interleukin-15 ; Interleukin-1alpha ; Interleukin-6 ; Interleukin-8 ; Plasma ; Radial Artery ; RNA, Messenger ; Tumor Necrosis Factor-alpha

BACKGROUND/AIMS: Liver stiffness (LS) as assessed by transient elastography (TE) can change longitudinally in patients with chronic hepatitis B (CHB). The aim of this study was to identify the factors that improve LS. METHODS: Between April 2007 and December 2012, 151 patients with CHB who underwent two TE procedures with an interval of about 2 years were enrolled. Ninety-six of the 151 patients were treated with nucleos(t)ide analogues [the antiviral therapy (+) group], while the remaining 55 patients were not [the antiviral therapy (-) group]. The two groups of patients were stratified according to whether they exhibited an improvement or a deterioration in LS during the study period (defined as an LS change of < or =0 or >0 kPa, respectively, over a 1-year period), and their data were compared. RESULTS: No differences were observed between the antiviral therapy (+) and (-) groups with respect to either their clinical characteristics or their initial LS. The observed LS improvement was significantly greater in the antiviral therapy (+) group than in the antiviral therapy (-) group (-3.0 vs. 0.98 kPa, P=0.011). In the antiviral therapy (+) group, the initial LS was higher in the LS improvement group (n=63) than in the LS deterioration group (n=33; 7.9 vs. 4.8 kPa, P<0.001). However, there were no differences in any other clinical characteristic. In the antiviral therapy (-) group, the initial LS was also higher in the LS improvement group (n=29) than in the LS deterioration group (n=26; 8.3 vs. 6.5 kPa, P=0.021), with no differences in any other clinical characteristic. CONCLUSIONS: A higher initial LS was the only factor associated with LS improvement in patients with CHB in this study.
Adult ; Aged ; Alanine Transaminase/blood ; Antiviral Agents/therapeutic use ; DNA, Viral/blood ; Elasticity Imaging Techniques ; Female ; Hepatitis B e Antigens/blood ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/drug therapy/pathology/*ultrasonography ; Humans ; Logistic Models ; Longitudinal Studies ; Male ; Middle Aged