Anti-monocyte chemoattractant protein 1 gene therapy attenuates experimental chronic pancreatitis induced by dibutyltin dichloride in rats.

BACKGROUND: Monocyte chemoattractant protein 1 (MCP-1) is a member of the C-C chemokine family and exerts strong chemoattractant activity in monocytes, macrophages, and lymphocytes. Rat pancreatic fibrosis induced by dibutyltin dichloride (DBTC) is considered to be an appropriate chronic pancreatitis model histologically and enzymatically, as has demonstrated in a previous study. AIM: We examined the effect of human dominant negative inhibitor of MCP-1 (mutant MCP-1) on progression of chronic pancreatitis induced by DBTC in a rat model. METHODS: We used the experimental model of chronic pancreatitis induced by DBTC in rats. Mutant MCP-1 or empty plasmid at a dose of 50 microg/body weight was administrated into rat thigh muscles on days 4, 11, and 18 after administration of DBTC. On days 14 and 28, we evaluated the effect of mutant MCP-1 morphologically and biochemically. RESULTS: The mutant MCP-1 treated group inhibited early pancreatic inflammation and later pancreatic fibrosis histologically, and showed a decrease in serum MCP-1 concentration, intrapancreatic hydroxyproline, alpha-smooth muscle actin, and an increase in intrapancreatic amylase and protein content compared with the empty plasmid treated group. The mutant MCP-1 group also inhibited intrapancreatic mRNA expression of cytokines and chemokines. CONCLUSIONS: : Our findings suggest that monocyte/macrophage recruitment and the systemic MCP-1 signal pathway contribute to progression of chronic pancreatitis, and that blockade of MCP-1 may suppress the development of pancreatic fibrosis.

[Effect of preventive measures against central venous catheter-related infection: retrospective study in our division for recent 10 years].

A study was made of 2202 central venous catheters (CVC), which were inserted for recent 10 years, to know the effect of preventive measures against CVC-related infection. We divided 10 years in 3 periods: 1987-1990 (the first period), 1991-1993 (the second period), and 1994-1996 (the third period). Preventive measures such as thorough antiseptic precaution, shortening of CVC dwelling time, and prohibition of injection from three-way stopcocks were taken after the second period. In the third period, semiclosed infusion system (I-system) was introduced to our division. A febrile catheterized patient (higher than 38 degrees C) was diagnosed as CVC-related infection when the fever dropped immediately (within 72 hours) after removal of CVC, or when the tip of the CVC was positive for culture. The rate of CVC-related infection in the second (9.9%) or the third (7.3%) period was significantly lower than that (14.0%) of the first period (p < 0.05 and p < 0.001, respectively). The mean dwelling time of CVC was 31.5 days for the first period, 27.0 days for the second period, and 24.8 days for the third period. The rate of long-term dwelling catheters (more than 29 days) in the second (34.5%) or the third (28.7%) period was significantly lower than that (40.5%) in the first period (p < 0.01 and p < 0.001, respectively). The index of CVC-related infection (incidence of infection per 1,000 days) was 4.8 for the first period, 3.7 for the second period, and 2.9 for the third period. The rate of infection of short-term dwelling CVC (less than 28 days) in the second (9.5%) or the third (6.3%) period was significantly lower than that (16.0%) of the first period (p < 0.01 and p < 0.001, respectively). As to cultures of CVC and/or blood sample, the isolation rate of fungi decreased significantly (p < 0.001), and that of gram-negative rods showed a tendency to increase after the second period. It was concluded that shortening of CVC dwelling time and application of semiclosed infusion system were effective to reduce the rate of CVC-related infection.