A total pollutant load control system (TPLCS) was implemented in the Seto Inland Sea in 1979 to reduce the water pollution and the frequency of red tides. We estimated primary production from 1981 to 2010 to determine the effects of reducing the nutrient loadings from the surrounding land. While primary production has decreased overall in the Seto Inland Sea in response to the TPLCS and the associated reductions in the total nitrogen (T-N) and phosphorus (T-P) loads from land since 1981, the reductions were limited to 4 of its 11 subareas. Primary production has increased in the Harima Nada but has been stable in the Bingo Nada subarea, reflecting the fact that the T-N and T-P stocks have not decreased in these subareas over the study years. The inconsistent responses of the 11 subareas suggest that the characteristics of each subarea should be considered when environmental management measures are established and implemented in the Seto Inland Sea. The controls on the nutrient loadings according to the TPLCS should be modified to permit better management of this semi-enclosed sea.

Although meropenem is commonly used for intra-abdominal infections, its penetration into the abdominal cavity is not well understood. Meropenem (500 mg) was administered intravenously to 8 patients with inflammatory bowel diseases undergoing laparotomy. The drug concentrations were analyzed and used for a Monte Carlo simulation with minimum inhibitory concentration (MIC) data. Meropenem concentrations in peritoneal fluid (PF) and plasma were similar at 1 h after the end of a 0.5-h infusion. The probabilities of target achievement of drug concentrations over the MIC in PF for 40% of the dosing interval with 500 mg every 8 h and 1000 mg every 8 h, were 84% and 90% against Bacteroides spp., 98% and 99% against Escherichia coli , and 76% and 83% against Pseudomonas aeruginosa, respectively. In conclusion, meropenem penetrated PF well, and 500 mg every 8 h or 1000 mg every 8 h would be suitable for the therapy for intraabdominal infections.

The present study aimed to examine the peritoneal pharmacokinetics and pharmacodynamic exposure of intravenous cefotiam. One gram of cefotiam was administered to eight patients before abdominal surgery. Venous blood and peritoneal fluid (PF) samples were obtained at the end of infusion (0.5 h) and 1, 2, 3, 4, 5, and 6 h afterwards. The drug concentrations in the plasma and PF were determined, analyzed pharmacokinetically, and used for a stochastic simulation with minimum inhibitory concentration (MIC) data. Cefotiam penetrated well into the PF with the area under the drug concentration-time curve ratio of 0.88 +/- 0.18 (mean +/- SD, n = 8). Regarding the pharmacodynamic exposures against Escherichia coli and Klebsiella species, the probabilities of attaining the bacteriostatic target (40% of the time above MIC) in the PF using 0.5 g every 12 h, 1 g every 12 h, and 2 g every 12 h were 88.3-93.6%. However, 1 g every 8 h was needed for 89.7 and 91.6% probabilities of attaining the bactericidal target (70% of the time above MIC). These results should help us to understand better the peritoneal pharmacokinetics of cefotiam while also helping us to choose the appropriate dosage for intra-abdominal infections.