BACKGROUND/AIMS: Hepatic fibrosis in rat induced by thioacet amide shares similar morphological and biochemical characteristics with human liver cirrhosis. Thioacetamide (T AA) initially induces accumulation of collagen in Disse space and eventually leads to macro- and micronodular cirrhos is. Ito cell was believed to play a main role in hepatic fibrosis. And it s activity was known to be regulated by the expression of various genes. But little has been discovered about the upstream signal trans duction pathway of these genes in hepatic fibrosis. The expression of genesrelated to Ito cell activity was regulated by many transcription factors , the activity of which was regulated by protein kinase C( PKC) is oforms. So it is s upposed that PKC could be as s ociated with fibrosis in liver. METHODS: We investigated the correlation of PKC is oforms and It ocell activity in the course of hepatic fibrosis using TAA induced rat liver cirrhosis model. We used six week- old male rats , and administered 0.03% TAA in drinking water. The animals were sacrificed at 9, 20, and 30 weeks after TAA administration. The degree of hepatic fibrosis was evaluated by measuring the total amount of collagen.-SMA immunohist ochemical st aining of liver tissue was done to determine the Ito cell activity. The expression pattern of PKC isoforms was investigated by West ern blotting. RESULTS: In TAA- treated group, collagen cont ent and Ito cell activity did not increase until 30 weeks and 20 weeks of treatment , respectively, while in control group collagen cont ent and Ito cell activity were not detected. Collagen content showed linear correlation with Ito cell activity. This implied that the proliferation of activated Ito cells was prior to the increase of collagen content. In view of expression pattern of PKC is oforms, PKC alpha showed no difference in TAA- treated group and control group. In TAA-treated group, PKCbeta1 exhibited increased level of expression in both particulate and cytosolic forms at 9 weeks, while PKCdelta and PKC epsilon showed striking shift to particulated form. After 20 weeks, all of the PKC beta1, delta, and epsilon degenerated and showed remarkably decreased level of expression. This suggested PKC alpha had no relation to hepatic fibrosis,while PKC beta1, delta, and epsilon, showing activity at 9 weeks, were related to fibrosis og liver. In response to fibrogenic factors, molecules engaged in intracellular signal transduction pathway like PKC beta1, delta, and epsilon, began to change prior to the increase of Ito cell activity, morphologic changes and alterations of collagen content. CONCLUSION: Our results strongly suggest that the activity of PKC isoforms play an important role in early step of hepatic fibrosis, while accompanying Ito cell activity do in later step.
Animals ; Collagen ; Cytosol ; Drinking Water ; Fibrosis ; Hepatic Stellate Cells ; Humans ; Liver Cirrhosis* ; Liver* ; Male ; Protein Isoforms ; Protein Kinase C-epsilon ; Protein Kinases ; Rats ; Signal Transduction ; Strikes, Employee ; Thioacetamide ; Transcription Factors

BACKGROUND: E-cadherin, cortactin, and matrix metalloproteinase (MMP)-9 have roles in tumor development or progression, but their expression has not been fully investigated in pseudoepitheliomatous hyperplasia (PEH) and squamous cell carcinoma (SCC) of the head and neck. METHODS: We evaluated the immunohistochemical expression of E-cadherin, cortactin, and MMP-9 in 29 cases of PEH and 97 cases of SCC. Additionally, we evaluated their relationship with clinicopathologic factors and prognostic implications in SCC. RESULTS: Thirty-five cases of SCC showed reduced expression of E-cadherin, whereas none of the PEH did. A total of 20 cases and 11 cases of SCC were immunoreactive for cortactin and MMP-9, respectively, whereas none of the PEH did. In SCC, reduced expression of E-cadherin was correlated with cortactin expression and invasion depth. Cortactin expression was correlated with differentiation, T classification, and recurrence and/or metastasis. MMP-9 expression was correlated with invasion depth. Cortactin expression was correlated with poor overall survival and relapse-free survival and it was an independent prognostic factor. CONCLUSIONS: The reduced expression of E-cadherin and the expression of cortactin may be helpful for the differential diagnosis of PEH and SCC. Furthermore, cortactin expression in association with reduced E-cadherin expression is correlated with poor prognosis in SCC.
Cadherins ; Carcinoma, Squamous Cell ; Cortactin ; Diagnosis, Differential ; Head ; Head and Neck Neoplasms ; Hyperplasia ; Matrix Metalloproteinase 9 ; Neoplasm Metastasis ; Prognosis ; Recurrence

The aminoglycoside antibiotics is widely used in the treatment of infectious caused by gram-negative bacteria and for synergistic effect with(beta-lactam antibiotics. However, its therapeutic usefulness is limited by this potential nephrotoxicity and by disturbance of electrolyte homeostasis resulting in hypomagnesemia, hypokalemia, hypocalcemia such as Bartter-like syndrome. Many case repots have been reported on development of Bartter-like syndrome after aminoglycosides administration. But these reports had the many differences of such as types of aminoglycosides, age of patients, duration and total dose of treatment, combined antibiotics and baseline diseases. Therefore, the purpose of this study is to assess the effects of micronomocin sulfate on magnesium, calcium and potassium status of patients in acute pyelonephritis. Twenty one patients in acute pyelonephritis(18 female/3 male, ages 20-75) was treated with single or combined antibiotics. Eleven of twenty one patients as study group were treated with both micronomicin sulfate(aminoglycoside, 4mg/kg/day, during 5-8days) and flomoxef sodium (3rd cephalosporine, 2g/day, during 5-8days), and ten of twenty one patients as control group were treated only with flomoxef sodium(3rd cephalosporine. 2g/day. during 5-8days). Renal values, plasma and urinary electrolytes were measured before and at the end of IV antibiotic therapy. After micronomicin sulfate administrated for 6.4+/-1.5days, serum Mg, Ca, K, FEMg (fractional excretion of Mg), TTKG(transtubular K concentration gradient) and FECa(fractional excretion of Ca) did not significantly change(p>0.05). Therefore, those results suggest that micromonicin sulfate therapy within dose of 240mg/day(4mg/kg/day) for 6.4+/-1.5days may not cause disturbance of electrolyte homeostasis such as Bartter-like syndrome in acute pyelonephritis. Howerever, electrolyte disturbance is an important complication when aminoglycosides is given in larges doses over extended periods. Therefore, monitoring of blood concentration and urinary losses of electrolyte should be carried out along with careful observation of Bartter-like syndrome.
Aminoglycosides ; Anti-Bacterial Agents ; Calcium ; Electrolytes ; Gram-Negative Bacteria ; Homeostasis ; Humans ; Hypocalcemia ; Hypokalemia ; Magnesium ; Male ; Plasma ; Potassium ; Pyelonephritis* ; Sodium