Characterization of metabolites of clozapine N-oxide in the rat by micro-column high performance liquid chromatography/mass spectrometry with electrospray interface

The metabolism of clozapine N-oxide was investigated in the rat ({ce:inline-formula}n = 6{/ce:inline-formula}) after a single oral dose of 20 mg kg ⁻¹. The organic extracts of rat urine were separated by conventional high performance liquid chromatography (HPLC) and individual collected fractions were analyzed by micro-column electrospray HPLC/mass spectroscopy. The compounds identified in rat urine were clozapine N-oxide, clozapine, {ce:inline-formula}N-desmethylclozapine{/ce:inline-formula}, 8-deschloro-8-hydroxyclozapine, 8-deschloro-8-thiomethylclozapine, {ce:inline-formula}N-desmethylclozapine{/ce:inline-formula}, 8-deschloro-8-hydroxyclozapine, 8-deschloro-8-thiomethylclozapine, {ce:inline-formula}N-desmethyl-8-deschloro-8-thiomethylclozapine{/ce:inline-formula} and 8-deschloro-8-methylsulfinylclozapine. With the exception of the unchanged clozapine N-oxide, no other metabolite containing a N-oxide functional group could be found, the concentrations of clozapine N-oxide, clozapine and {ce:inline-formula}N-desmethylclozapine{/ce:inline-formula} excreted from rat urine were determined utilizing a conventional HPLC procedure with UV detection. The recoveries of these three analytes reported as the percentage of the dosage from the 0.24 h urine are {ce:inline-formula}0.93 ± 0.54%, 0.06 ± 0.03%and0.01 ± 0.006%{/ce:inline-formula} respectively.     

Fast neutron sensor for detection of explosives and chemical warfare agents

Once the presence of the anomaly on the bottom of the shallow coastal sea water has been confirmed it is necessary to establish if it contains explosive or chemical warfare charge. We propose that this be performed by using neutron sensor installed within an underwater vessel. When positioned above the object, or to its side, the system can inspect the object for the presence of the threat materials by using alpha particle tagged neutrons from the sealed tube d+t neutron generator.     

Spatial distribution of Echinococcus multilocularis, Svalbard, Norway

In Svalbard, Norway, the only intermediate host for Echinococcus multilocularis, the sibling vole, has restricted spatial distribution. A survey of feces from the main host, the arctic fox, showed that only the area occupied by the intermediate host is associated with increased risk for human infection.     

PM2.5 collected in China causes inflammatory and oxidative stress responses in macrophages through the multiple pathways

Air pollution continues to increase in East Asia, particularly in China, and is considered to cause serious health problems. In this study, we investigated the toxicological properties of particulate matter ≤2.5 mm (PM_2.5) collected in an urban area in China (Shenyang), focusing on inflammation and oxidative stress tightly linked to respiratory diseases. Exposure to PM_2.5 significantly increased the expression levels of inflammatory (interleukin-1β and cyclooxygenase-2) and oxidative stress (heme oxygenase1) genes in the mouse macrophages. PM_2.5-caused inflammatory response was strongly suppressed by endotoxin neutralizer (polymyxin B) and knock-out of toll-like receptor 4, while oxidative stress was not. On the other hand, an antioxidant (N-acetylcystein) suppressed oxidative stress, but not inflammatory response. These results suggest that PM_2.5 in the atmospheric environment of China causes inflammation and oxidative stress in macrophages via separate pathways.     

Type 1 diabetes and pregnancy

Type 1 diabetes in pregnancy presents multiple challenges to healthcare groups. Although there are debates regarding the precise pathophysiology of the different complications of type 1 diabetes during pregnancy, there is increasing evidence that good periconception and early pregnancy glycaemic control will reduce the rate of all complications, including macrosomia. The provision of organized prepregnancy care for this group allows an opportunity to reinforce the need for tight glycaemic control, to commence vitamin supplementation, to identify those with complications of diabetes who require more specialist evaluation and preparation, and to inform women of pregnancy risks. How this type of detailed care is provided is a major organizational issue for all healthcare systems. Optimal outcome during pregnancy is achieved by intense management by both obstetric and diabetic services. Many interventions and strategies during pregnancy, including the degree of glycaemic control, have a poor evidence base. The demands on pregnant women with type 1 diabetes should not be underestimated.