Anaerobic biodegradation of aircraft deicing fluid in UASB reactors.

A central composite design was employed to methodically investigate anaerobic treatment of aircraft deicing fluid (ADF) in bench-scale Upflow Anaerobic Sludge Blanket (UASB) reactors. A total of 23 runs at 17 different operating conditions (0.8% 1.6% ADF (6000-12,000mg/L COD), 12-56h HRT, and 18-36gVSS/L) were conducted in continuous mode. The development of four empirical models describing process responses (i.e. COD removal efficiency, biomass-specific acetoclastic activity, methane production rate, and methane production potential) as functions of ADF concentration, hydraulic retention time, and biomass concentration is presented. Model verification indicated that predicted responses (COD removal efficiencies, biomass-specific acetoclastic activity, and methane production rates and potential) were in good agreement with experimental results. Biomass-specific acetoclastic activity was improved two-fold from 0.23gCOD/gVSS/d for inoculum to a maximum of 0.55gCOD/gVSS/d during ADF treatment in UASB reactors. For the design window, COD removal efficiencies were higher than 90%. The predicted methane production potentials were close to theoretical values, and methane production rates increased as the organic loading rate is increased. ADF toxicity effects were evident for 1.6% ADF at medium organic loadings (SOLR above 0.5gCOD/gVSS/d). In contrast, good reactor stability and excellent COD removal efficiencies were achieved at 1.2% ADF for reactor loadings approaching that of highly loaded systems (0.73gCOD/gVSS/d).

Determining the full costs of medical education in Thai Binh, Vietnam: a generalizable model.

We summarize a model for determining the full cost of educating a medical student at Thai Binh Medical School in Vietnam. This is the first full-cost analysis of medical education in a low-income country in over 20 years. We emphasize policy implications and the importance of looking at the educational costs and service roles of the major health professions. In Vietnam fully subsidized medical education has given way to a system combining student-paid tuition and fees with decreased government subsidies. Full cost information facilitates resource management, setting tuition charges at a school and adjusting budget allocations between medical schools, teaching hospitals, and health centres. When linked to quality indicators, trends within and useful comparisons between schools are possible. Cost comparisons between different types of providers can assist policy-makers in judging the appropriateness of expenditures per graduate for nursing and allied health education versus physician education. If privatization of medical education is considered, cost analysis allows policy-makers to know the full costs of educating physicians including the subsidies required in clinical settings. Our approach is intuitively simple and provides useful, understandable new information to managers and policy-makers. The full cost per medical graduate in 1997 was 111 462 989 Vietnamese Dong (US$9527). The relative expenditure per Vietnamese physician educated was 2.8 times the expenditure in the United States when adjusted for GNP per capita. Preliminary findings suggest that, within Vietnam, the cost to educate a physician is 14 times the cost of educating a nurse. Given the direct costs of physician education, the lifetime earnings of physicians and the costs that physicians generate for the use of health services and supplies, it is remarkable that so little attention is paid to the costs of educating physicians. Studies of this type can provide the quantitative basis for vital human resource and health services policy considerations.

Methotrexate: assessment of in vivo clastogenicity and carcinogenicity.

The genotoxic and oncogenic potentials of methotrexate were studied in Sprague-Dawley rats. The rats received 0.1, 0.2, or 0.4 mg/kg of methotrexate as dietary admixtures on a 5 days on, 9 days off, regimen for 23 months. In the females of the high-dose group, there was a significant increase in mortality starting at 18 months. Significant increases in the number of rats with focal pulmonary interstitial fibrosis were seen in both sexes at the high-dose level. At the mid- and high-dose levels of both sexes, there was a significantly increased number of rats with myeloid and erythroid bone marrow hypoplasia. There was no evidence of either early onset or increased incidence of any tumor type in the treatment groups. Therefore, it is concluded that methotrexate does not have oncogenic potential. Also, at terminal sacrifice, bone marrow cells were harvested from selected animals on the last day of the 5-day dosing cycle and cytogenetic evaluation was performed. No significant increase in chromosomal aberrations was seen in any dose group relative to the control group. This observation further substantiates the absence of oncogenic potential due to methotrexate in rats.

The effect of mitoxantrone treatment in beagle dogs previously treated with minimally cardiotoxic doses of doxorubicin.

Low-grade chronic cardiotoxicity as determined by myocardial biopsy specimens was induced in beagle dogs after four courses of doxorubicin hydrochloride (1.64 mg/kg, 34.0 mg/sq m) given intravenously once every 3 weeks. After this initial treatment, these dogs were separated into three groups. Two groups received six courses of mitoxantrone (0.25 mg/kg, 5 mg/sq m) commencing at 7 weeks or 19 weeks after the final doxorubicin treatment. The third group was treated with six additional courses of doxorubicin after an interval of 7 weeks. Up to seven sequential endomyocardial biopsies were performed to monitor the myocardial changes which were observed after the initial doxorubicin treatment. The low-grade cardiotoxic changes progressed for at least 7-11 weeks without any additional doxorubicin treatment, and stabilized or even partially reversed after 19 weeks of a treatment-free period. Dogs that received additional doxorubicin demonstrated progressive cardiotoxicity, associated with clinical signs, that resulted in death after a total of seven to ten courses of treatment (12-16 mg/kg, 238-340 mg/sq m cumulative dose). In dogs treated with doxorubicin followed by mitoxantrone after a 19-week treatment-free period, myocardial changes were shown to have stabilized and/or partially regressed. This study indicated that in beagle dogs four courses of doxorubicin (7 mg/kg, 136 mg/sq m cumulative dose) are the threshold dose at which non-life-threatening cardiotoxicity occurs. Residual toxic effects of doxorubicin may be erroneously interpreted as adverse findings attributable to other agents given subsequently during the susceptible period, ie, prior to stabilization of the myocardium. Mitoxantrone given after stabilization of doxorubicin-induced low-grade myocardial changes did not show additive or synergistic effects.

Effects of oxygenated derivatives of cholesterol on cholesterol uptake by cultured aortic smooth muscle cells.

The cytotoxicity of oxygenated derivatives of cholesterol on the cultured cells may not only be due to their potent inhibition of cholesterol biosynthesis, but also could be related to their capability for inhibiting cholesterol uptake from exogenous sources, particularly in arterial cells, which synthesize cholesterol at a very slow rate. In cultured aortic smooth muscle cells, the most potent inhibitor of cholesterol uptake was cholestane-3 beta,5 alpha,6 beta triol, which at 100 micrograms/ml medium reduced uptake of cholesterol to 10% of the control. The next most potent inhibitors were 5 alpha,6 alpha- epoxycholesterol and 25-hydroxycholesterol, which reduced uptake of cholesterol to 60%. 7 alpha- and 7 beta-hydroxycholesterol and 7-ketocholesterol inhibited cholesterol uptake to 30-50%. A consequence of their inhibitory effects on cholesterol uptake could be a depletion of cell membrane cholesterol, resulting in alterations in membrane structure and function and eventually in cell death.

Cytotoxicity of oxidation derivatives of cholesterol on cultured aortic smooth muscle cells and their effect on cholesterol biosynthesis.

Aortic smooth muscle cell death is an important initial lesion of atherosclerosis. A number of autooxidation products of cholesterol which has been recognized recently has the capability of inducing rabbits' aortic smooth cell death in vitro. Twelve oxidation derivatives of cholesterol, available commercially, were dissolved in small amounts of ethanol, then added to the culture medium at levels not exceeding 0.8%. The medium contained 10% fetal calf's serum which served as an in situ vehicle for the sterols. The degrees of cytotoxicity were graded and measured as percentage of dying and dead cells in the cultures within 24 hr. 25-Hydroxycholesterol and cholesthan-3 beta, 5 alpha, 6 beta-triol, were the most toxic compounds among the sterols tested. When these oxidation derivatives of cholesterol were added to these cultured cells, they significantly depressed activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, a regulatory enzyme of cholesterol biosynthesis (up to 83% inhibition by 25 hydroxycholesterol at a 3 microgram/ml concentration in culture medium) but the sequence of degree of inhibition was not exactly correlated with that of cytotoxicity. Various mechanisms are speculated. Purified cholesterol showed no cytotoxic effect and minimal inhibition of cholesterol biosynthesis.

Effect of auto-oxidation products from cholesterol on aortic smooth muscle cells: an in vitro study.

Purified cholesterol is quite unstable when stored in air at room temperature. Products of cholesterol auto-oxidation were concentrated from several lots of USP-grade cholesterol by recrystallizing cholesterol from the methanol extract, retaining the mother liquor, and evaporating the residuum to dryness under vacuum. By application of thin-layer chromatography and gas-liquid chromatography, major, individual, oxidation compounds were identified and quantitated. Biological activities of these oxidation compounds were studied by using cultured rabbits' aortic smooth muscle cells. The concentrate of the auto-oxidation products of cholesterol showed remarkable in vitro cytotoxic effects, whereas purified cholesterol at the same concentration produced no toxic effects. The concentrate was further separated into six thin-layer chromatographical fractions. The results showed that 25-hydroxycholesterol and cholestane-3beta, 5alpha, 6beta-triol were probably responsible for the biological toxicity of the concentrate