Use of stable 48Ca in the clinical measurement of intestinal calcium absorption

Measurements of intestinal-calcium-absorption efficiency are fundamental for understanding calcium homeostasis in health and disease. Stable calcium isotopes are attractive tracers for such measurements, to avoid excessive radiation exposure to the subject and permit serial studies at short intervals. To realize this, we found it necessary to improve the sensitivity and precision of existing thermal neutron activation analyses for 48Ca. This report describes the details, sensitivity, precision, and accuracy of the improved method, and gives the results of studies in which intravenous 48Ca was used in conjunction with oral 47Ca to measure intestinal-calcium-absorption efficiency in patients.     

Identification of bacteria crucial to histamine accumulation in pacific mackerel during storage

Bacterial growth and histamine formation in Pacific mackerel during storage at 0, 4, 15, and 25 degrees C were monitored. To identify bacterial species contributing to histamine formation, several groups of bacteria were isolated by using selective media under temperatures corresponding to the various storage conditions. Initially, low counts of bacteria were found in the gill, skin, and intestine of fresh fish, and only weak histamine formers were found in the gill. Histamine was found in the muscle when fish were stored above 4 degrees C, and aerobic plate counts reached 10(6) CFU/g. When fish became unsuitable for human consumption by abusive storage, toxicological levels of histamine were always found. The highest level of histamine formed was 283 mg/100 g in 2 days. The optimum temperature for supporting growth of prolific histamine formers was 25 degrees C. The most prolific and prevalent histamine former was Morganella morganii, followed by Proteus vulgaris, both of which were isolated on violet red bile glucose (VRBG) agar. At 15 degrees C, a significant level of histamine was still produced in fish muscle, although prolific histamine formers were less frequently detected than at 25 degrees C. The isolates on thiosulfate citrate bile salts sucrose (TCBS) agar were weak histamine formers and identified as Vibrio parahaemolyticus and Vibrio alginolyticus. At 4 degrees C, less than 57.4 mg/100 g of histamine was found in fish stored for 14 days. Most isolates were natural bacterial flora in the marine environment and identified as weak histamine formers. At 0 degrees C, neither histamine former nor histamine production was detected up to 14 days of storage.     

An approximate compositional approach to the analysis of fluid queue networks

Fluid models have for some time been used to approximate stochastic networks with discrete state. These range from traditional ‘heavy traffic’ approximations to the recent advances in bio-chemical system models. Here we present a simple approximate compositional method for analysing a network of fluid queues with Markov-modulated input processes at equilibrium. The idea is to approximate the on/off process at the output of a queue by an n-state Markov chain that modulates its rate. This chain is parameterised by matching the moments of the resulting process with those of the busy period distribution of the queue. This process is then used, in turn, as a separate Markov-modulated on/off process that feeds downstream queue(s). The moments of the busy period are derived from an exact analytical model. Approximation using two- and three-state intermediate Markov processes are validated with respect to an exact model of a tandem pair of fluid queues — a generalisation of the single queue model. The analytical models used are rather simpler and more accessible, albeit less general, than previously published models, and are also included. The approximation method is applied to various fluid queue networks and the results are validated with respect to simulation. The results show the three-state model to yield excellent approximations for mean fluid levels, even under high load.     

The relative effectiveness of exposure to 131I at low doses

BACKGROUND: Reactive oxygen and nitrogen derived species produced by activated neutrophils have been implicated in the damage of mucosal proteins including the inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the active inflammatory lesion in patients with inflammatory bowel disease (IBD). This study investigated the efficacy of currently used IBD therapeutics to prevent injury mediated by reactive oxygen and nitrogen derived species. METHODS: GAPDH activity of human colon epithelial cells was used as a sensitive indicator of injury produced by reactive oxygen and nitrogen derived species. HCT116 cells (10(6)/ml phosphate buffered saline; 37 degrees C) were incubated in the presence of 5-aminosalicylic acid (5-ASA), 6-mercaptopurine, methylprednisolone, or metronidazole before exposure to H2O2, HOCl, or NO in vitro. HCT116 cell GAPDH enzyme activity was determined by standard procedures. Cell free reactions between 5-ASA and HOCl were analysed by spectrophotometry and fluorimetry to characterise the mechanism of oxidant scavenging. RESULTS: GAPDH activity of HCT116 cells was inhibited by the oxidants tested: the concentration that produced 50% inhibition (IC50) was 44.5 (2.1) microM for HOCl, 379.8 (21.3) microM for H2O2, and 685.8 (103.8) microM for NO (means (SEM)). 5-ASA was the only therapeutic compound tested to show efficacy (p<0. 05) against HOCl mediated inhibition of enzyme activity; however, it was ineffective against H2O2 and NO mediated inhibition of GAPDH. Methylprednisolone, metronidazole, and the thiol-containing 6-mercaptopurine were ineffective against all oxidants. Studies at ratios of HOCl:5-ASA achievable in the mucosa showed direct scavenging to be the mechanism of protection of GAPDH activity. Mixing 5-ASA and HOCl before addition to the cells resulted in significantly greater protection of GAPDH activity than when HOCl was added to cells preincubated with 5-ASA. The addition of 5-ASA after HOCl exposure did not restore GAPDH activity. CONCLUSIONS: Therapies based on 5-ASA may play a direct role in scavenging the potent neutrophil oxidant HOCl, thereby protecting mucosal GAPDH from oxidative inhibition. These findings suggest that strategies for the further development of new HOCl scavenging compounds may be useful in the treatment of IBD.