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The objective of this review was to conduct a comprehensive literature survey to identify the parameters that govern the permeate flux in an anaerobic membrane bioreactor (AnMBR) treating municipal wastewater. Based on the survey, research to date indicates that the optimal membrane system for an AnMBR consists of an organic, hydrophilic, and negatively charged membrane with a pore size of approximately 0.1 microm. The use of both external and submerged membrane configurations shows promise. The operating parameters that affect permeate flux in an external membrane system are transmembrane pressure (TMP) and cross-flow velocity. The operating parameters that affect permeate flux in a submerged membrane system are TMP, sparging intensity, and duration of the relaxation period. Both cross-flow velocity and sparging intensity impart a significant amount of shear force on the biomass in an AnMBR. High shear forces can reduce the microbial activity in an AnMBR. In addition, high shear forces can reduce the size of the biosolids in the mixed liquor and increase the release of soluble microbial products. In this respect, external and submerged membrane systems are expected to perform differently because the magnitude of the shear forces to which the biomass is exposed in an external membrane system is significantly greater than that in a submerged system. The size of the biosolid particles and concentration of soluble microbial products in the mixed liquor affect permeate flux. Higher concentrations of soluble microbial products may be present in the mixed liquor when an AnMBR is operated at relatively low operating temperatures. Aerobic polishing following anaerobic treatment can potentially significantly reduce the concentration of some components of the soluble microbial products in the mixed liquor. It is not possible to remove the foulant layer on an organic membrane with caustic cleaning alone. Acidic cleaning or acidic cleaning followed by caustic cleaning is required to remove the foulant layer. This suggests that both biological/organic and inorganic material contribute to membrane fouling.

Pulp and paper mill effluents (PPMEs) are believed to contain some naturally occurring endocrine disrupting chemicals (EDCs) such as phytosterols or plant sterols, which may be related to a variety of physiological and morphological abnormalities in fish inhabiting receiving waters. Analyses of effluent streams from two Canadian pulp mills confirmed the presence of five different phytosterols in PPMEs. Sterol contents of biologically treated as well as untreated effluents are presented. ββ-Sitosterol, ββ-sitostanol (or stigmastanol), and campesterol formed the major fraction of plant sterols in PPMEs, accounting for 70 % or more of the total phytosterol content measured. Sterols entering the activated sludge treatment systems were generally removed from the effluents with average removal efficiencies of 72 and 66% for the two mills surveyed. Sorption and biodegradation may be responsible for the observed removal of plant sterols across the biological wastewater treatment systems. Key words: ββ-sitosterol, stigmastanol, campesterol, removal and mass flow of phytosterols or plant sterols, hormone disruptors, pulp mill effluents, activated sludge, industrial wastewater treatment.

Adsorption using powdered activated carbon and coagulation using polyaluminium chloride or aluminum sulphate were investigated as pretreatment steps prior to membrane filtration to remove organic material and trihalomethane (THM) precursors contained in a raw drinking water source. Ultrafiltration and microfiltration membrane treatment alone could not effectively and consistently remove organic material, measured as total organic carbon, and THM precursors, measured as chloroform formation potential, contained in the raw water. Coagulation, prior to membrane treatment, significantly improved the removal of organic material and THM precursors contained in the raw water. Microfiltration membrane treatment, with pre-coagulation, consistently removed approximately 75% of the organic material and the THM precursors contained in the raw water. A coagulant concentration of approximately 0.3 mg/L, as Al, was sufficient to achieve this high removal efficiency. Adsorption, prior to membrane treatment, did not significantly improve the removal of organic material or THM precursors. Key words: adsorption, chloroform, coagulation, disinfection-by-products, drinking water treatment, microfiltration, trihalomethanes, ultrafiltration.

This study investigated the removal of methanol from kraft pulp mill condensate using a high temperature membrane bioreactor (MBR). The effects of the complex matrix associated with real condensate, on methanol metabolism and removal kinetics, were examined. The measured specific methanol utilization rate observed during the treatment of real condensate was lower than that previously observed with synthetic condensate. The difference could not be attributed to inhibitory effects of the real condensate matrix. Instead, the reduction was attributed to a shift in the composition of the microbial community present in the MBR. The shift resulted from competition between non-methylotrophic and methylotrophic microorganisms for the available methanol. The non-methylotrophic microorganisms exhibited a lower specific methanol utilization rate (0.45/day) than the methylotrophic microorganisms (0.81/day), resulting in a lower overall specific methanol utilization rate of 0.55/day. Nonetheless, the specific methanol utilization rate observed in the present study at 60 °C was still more than 20 % higher than previously reported values from other studies of biological treatment of condensate at much lower temperatures.

The accuracy and utility of the dosimetry system used for radiation effects research with high energy protons at the Indiana University Cyclotron Facility, IUCF, has been confirmed by comparison with an independently calibrated Markus ion chamber, a Schulz water calorimeter and GAFCHROMIC/sup TM/ films.

An ultrafiltration system and a membrane biological reactor were operated in parallel to compare the removal efficiencies achieved for total and dissolved solids and chemical oxygen demand, from a simulated, low water-use, mechanical newsprint mill whitewater at 55°C. The ultrafiltration system was operated at water recovery fractions (Y) of 0.9, 0.95 and 0.983, while the membrane biological system was operated at water recovery fractions of 0.95, 0.975 and 0.983. In all cases, the membrane biological reactor exhibited higher removal efficiencies than the ultrafiltration system alone. The MBR demonstrated 48–58% removal of total COD, 35–45% removal of dissolved COD, 25–35% removal of total solids and 20–30% removal of dissolved solids. Maximum flux through the membranes was highest at lower water recovery fractions for both the ultrafiltration system and the membrane biological reactor. Fouling time, based on the time required for a 20% loss of flux, increased with increasing water recovery for the membrane biological reactor and decreased with water recovery fraction for the ultrafiltration system.

Spectra of microbial fatty acid methyl esters were used to assess the influence of pH on the biofilm and suspended biomass populations within bench scale moving bed bioreactors treating bleached kraft mill effluent. The fatty acid spectral data were reduced by logcontrast canonical component analysis. The first canonical component differentiated biofilm from suspended populations and the second two appeared to indicate an influence of pH on microbial ecology. Thus, the biofilm and suspended microbial communities were distinct, as were the populations acclimated at pH 6 and pH 8. Experimental data for total organic carbon removal suggested that the more recalcitrant fraction of the influent was consumed by the slower growing, high SRT biofilm fraction of the biomass. Since the biofilm ecology was sensitive to pH within typical pH operating limits of full-scale systems, tighter pH control might improve treatment reliability in the event of process transients.

The fate of phosphorus contained in waste activated sludges from a biological nutrient removal plant was investigated in pilot-scale, co-digestion studies at a full-scale wastewater treatment plant. In these studies, co-digestion of primary fermenter and waste activated sludges resulted in a significant release of the biologically-bound sludge phosphorus. As much as 80% of phosphate removed during treatment was released to the supernatant during anaerobic digestion. Phosphate release was found to be independent of digester hydraulic retention time at the values tested (20 vs. 10 day). Co-digestion also impacted other aspects of digester operation, including volatile solids reduction and total gas and methane production. Jar tests, conducted to evaluate the efficiency of various chemical treatment methods for removing phosphate from digester supernatants, revealed that lime, alum and ferric chloride all proved equally effective. Overall, ferric chloride at a dosage of 2 g l−1 was found to be the most effec...

On evalue dans cette etude le potentiel de la technologie d'ultrafiltration et du traitement biologique pour retirer de l'eau blanche en recirculation des contaminants tels que la quantite totale de matieres dissoutes (TDS), la demande chimique en oxygene (COD), le carbone organique total (TOC) et les acides gras et resineux (RFA). Des experiences d'ultrafiltration discontinues indiquent que les efficacites de retrait de TDS, COD soluble et TOC sont influencees par la coupure du poids moleculaire des membranes (masse molaire), mais qu'elles sont independantes de la temperature de fonctionnement, dans la gamme de 20 a 60°C. Sauf pour les acides gras, pour lesquels les retraits moyens excedent 90%, l'efficacite de separation du procede pour tous les autres parametres (TDS, COD soluble, TOC et acides resineux) est moyenne, allant de 10 a 41%. Le traitement biologique avec un reacteur discontinu sequence (SBR) s'est avere tres efficace pour le retrait des RFA, du TOC et de la COD totale et soluble. En outre, l'ultrafiltration de l'eau de procede traitee biologiquement a permis un retrait supplementaire significatif de la TDS, de la COD soluble et du TOC.

This paper illustrates the feasibility of the anaerobic membrane bioreactor concept for the treatment of segregated kraft bleach plant wastewaters by comparing AOX removal achievable by anaerobic biological treatment, ultrafiltration, and coupled anaerobic/ultrafiltration treatment. If high rate anaerobic treatment (UASB) is used as the base case for comparison, then long term AOX removal efficiencies of more than 48% in the other two systems would be indicative of superior performance. Similarly, the accumulation of less than 5% of the influent AOX in the reactor contents would result in lower levels of AOX in any waste streams removed from the systems for disposal. Judging from the long term cumulative mass balance data, AOX removal efficiencies were improved with the application of both ultrafiltration (54%) and anaerobic membrane bioreactor treatment (61%). However, the improvement in AOX removal achieved with ultrafiltration and anaerobic membrane bioreactor treatment was, at best, modest. Since it w...

Laboratory-scale activated sludge (AS), facultative stabilization basin (FSB) and aerated stabilization basin (ASB) processes were operated in parallel treating bleached kraft mill effluent under controlled SRT and temperature conditions, to assess the chlorinated phenolics removal efficiencies attainable in each. The structure and extent of chlorination of the chlorophenolic compounds monitored appeared to contribute to the differing removal efficiencies observed. Under most operating conditions, treatment process effluents contained chronically toxic levels of pentachlorophenol-equivalent toxicity (TEQ). A companson of the results obtained from the FSB, ASB and AS processes indicated that, under most operating conditions, chlorophenolics removal in low rate treatment systems is superior to that in a higher rate activated sludge treatment process. However, it was also observed that operation at long SRT and moderate temperature permitted enhanced removal of chlorophenolics and reduced TEQs to less than threshold values, in all three treatment processes.

Laboratory scale activated sludge (AS), facultative stabilization basin (FSB) and aerated stabilization basin (ASB) processes were operated under controlled parallel conditions to assess the AOX (adsorbable organic halogen) removal efficiencies attainable in each. A comparison of the results obtained under a variety of operating conditions indicated that higher removal efficiencies of total and filterable AOX were achieved in the FSB and ASB processes than in the AS system. Data are also presented to indicate the extent to which influent AOX was removed by biodegradation, biosorption and off-gas stripping.

Bovine lung thromboxane synthase was immobilized on phenyl-Sepharose beads by adsorption. The immobilized enzyme was catalytically active and synthesized both TXA2 and HHT. The production of both products was inhibited by 1-benzylimidazole and furegrelate. Multiple additions of PGH2 dramatically reduced the ability of the enzyme to synthesize TXA2, but did not effect the synthesis of HHT. In addition, 1-benzylimidazole did not protect thromboxane synthase from inactivation with multiple additions of PGH2. When the enzyme was incubated with PGH2 in the presence of 1-benzylimidazole, the synthesis of TXA2 was inhibited. When the inhibitor was removed the enzyme had still been inactivated by PGH2 in the presence of 1-benzylimidazole. Thus the substrate inactivation of the enzyme does not require the production of TXA2. Our data suggests that the synthesis of TXA2 and HHT can be differentially inactivated and may occur at different sites on the enzyme.

Infection caused by enterotoxigenic Escherichia coli (ETEC) poses a significant health problem in children and adults residing in endemic developing countries. Acute and convalescent paired stool and serum samples were obtained from 27 U.S. military personnel with ETEC-induced diarrhea during a military exercise in Egypt. In general, the concentration of total fecal and circulatory anti-LT IgA was significantly increased in convalescent specimens than in the paired acute ones in almost 65 % of the cases. The pattern of specific antibody responses in fecal and serum samples from cases with ETEC expressing the antigens coil surface 1 (CS1), CS2, CS3 and CS6 were, on the other hand, not conclusive due to the small numbers of the study cases. Further research is still required to understand the immunologic responses during the natural course of disease. The data obtained, nevertheless, may help current research efforts on the development of vaccines for humans against ETEC infection.

We describe two new beamlines for radiation effects research at the Indiana University Cyclotron Facility. Protons with energies up to 205 MeV are available. One of the beamlines offers momentum selected beams at energies as low as 52 MeV. Beam characteristics such as transmission, energy, energy spread and lateral profile are described and compared to calculations. The dosimetry with emphasis on the lower energies is discussed.

Activated Sludge Model No 3 (ASM3) was chosen to model an activated sludge system treating effluents from a mechanical pulp and paper mill. The high COD concentration and the high content of readily biodegradable substrates of the wastewater make this model appropriate for this system. ASM3 was calibrated based on batch respirometric tests using fresh wastewater and sludge from the treatment plant, and on analytical measurements of COD, TSS and VSS. The model, developed for municipal wastewater, was found suitable for fitting a variety of respirometric batch tests, performed at different temperatures and food to microorganism ratios (F/M). Therefore, a set of calibrated parameters, as well as the wastewater COD fractions, was estimated for this industrial wastewater. The majority of the calibrated parameters were in the range of those found in the literature.

We describe two new beamlines for radiation effects research at the Indiana University Cyclotron Facility. Protons with energies up to 205 MeV are available. One of the beamlines offers momentum selected beams at energies as low as 52 MeV.

High energy protons are useful for ground based simulation of the effects of space radiation on electronic devices and systems. Present and planned facilities to support the ongoing IUCF radiation effects research program (RERP), which uses protons with energies as high as 200 MeV, are described and results of high energy proton dosimetry studies are presented.

Two randomized, double-blinded trials assessed the safety and immunogenicity of an oral, killed enterotoxigenic Escherichia coli (ETEC) plus cholera toxin B subunit vaccine in Egyptian children. Two doses of vaccine or E. coli K-12 were given 2 weeks apart to 105 6- to 12-year-olds and 97 2- to 5-year-olds. Safety was monitored for 3 days after each dose. Blood was collected before immunization and 7 days after each dose to measure immune responses. Few children reported postdosing symptoms, with no differences in the frequency of symptoms between treatment groups. Most vaccinees had an IgA antibody-secreting cell response against colonization factor antigen I (100%, 6-12 years; 95%, 2-5 years), coli surface antigen 2 (92%, 6-12 years; 83%, 2-5 years), and coli surface antigen 4 (93%, 6-12 years). Vaccination evoked a/=4-fold rise in antitoxic IgA and IgG titers in 93% and 81% of children, respectively. In conclusion, the oral ETEC vaccine was safe and immunogenic in 2- to 12-year-old children, justifying further evaluation in infants.

Bovine lung thromboxane synthase was immobilized on phenyl-Sepharose beads by adsorption. The immobilized enzyme was catalytically active and synthesized both TXA 2 and HHT. The structure-activity relationship of several hydroperoxy fatty acids and their ability to inactivate thromboxane synthase was investigated. Millimolar quantities of hydrogen peroxide and tert-butylperoxide were required to inactivate the enzyme; whereas micromolar quantities of C 18 and C 20 hydroperoxy fatty acids inactivated the enzyme. Pretreatment of the enzyme with long chain hydroperoxy-fatty acids resulted in a decreased synthesis of both TXB 2 and HHT.

Publisher Summary The chapter presents a study on preparation of prostaglandin H 2 (PGH 2 ), discussing the extended purification/analysis scheme. PGH 2 is routinely prepared from ram seminal vesicles and isolated by gravity flow silicic acid chromatography. The chapter mentions the procedures that produce PGH 2 , which is contaminated with small amounts of HHT, HETEs, PGF 2α , PGE 2 , PGD 2 , and other unidentified nonarachidonic acid substances, and which has a purity that rarely exceeds 80%. The bonded-phase rechromatography methods described in the chapter provides homogeneous PGH 2 as assayed by high-performance liquid chromatography (HPLC) and ammonia, direct chemical ionization-mass spectrometry (DCI-MS). A fundamental limit to any technique used in the purification of PGH 2 resides in the reactivity of this molecule with protic solvents and silica-based adsorbents (presumably via the acidic Si-OH bond). A study evaluating various chromatography systems and solvents has shown that cyano-bonded, stationary-phase columns eluted with a hexane-2-propanol gradient is an effective means for further purification of PGH 2 .2-Propanol, used as the polar organic modifier in the mobile phase, appears to cause less PGH2 degradation than other alcohols that were tested. It is found that ammonia DCI-MS to be a particularly useful method for directly analyzing prostaglandin preparations, including those containing the labile PGH 2 molecule.

Arachidonic acid metabolism produces several biologically important compounds including the leukotrienes and prostaglandins. Prostaglandin H2 (PGH2) is the first metabolite in the arachidonic acid cascade leading to all other prostaglandins. Pivotal to our understanding of PGH2's biology is the ability to separate it in pure form from the numerous other arachidonic acid metabolites produced in a biological milieu. The extensive literature on PGH2 biology and metabolism has relied almost exclusively on the traditional method of separation using gravity flow silicic acid columns. In our hands, such PGH2 preparations were found to contain varying amounts of 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT), PGE2, PGF2 alpha and other minor impurities as determined by further chromatographic and mass spectral analyses. Analytical separation of PGH2 and other arachidonic acid metabolites has been accomplished using reversed-phase HPLC. However, the labile nature of this molecule in aqueous systems makes such techniques unacceptable for preparative isolation of high purity PGH2 and has necessitated the development of a totally nonaqueous separation. To this end, we attempted several stationary phases and found that the cyano-bonded phase showed the best selectivity for resolving PGH2 from its major contaminants. Separations were performed on self-packed columns using a hexane-isopropanol gradient. Peaks were detected both by liquid scintillation counting and uv spectrophotometry (214 nm). Structure assignments were made by chromatographic comparison with authentic standards (PGF2 alpha, PGE2), biological activity (PGH2--platelet aggregation), and by ammonia direct chemical ionization mass spectrometry (HHT, hydroxy-5,8,10,14-eicosatetraenoic acid, PGH2, PGE2, PGF2 alpha). The latter technique, which by its very nature volatilizes all organic material in the sample, was particularly useful in determining not only that the PGH2 preparations were free from the aforementioned side products, but that they were also free from lipid, protein, and other potential residues frequently found in biological preparations.

Human platelet thromboxane synthase was partially purified by DEAE-cellulose, Affi-Gel Blue, and Sephacryl S-300 chromatography to a specific activity of 259 nmol of thromboxane B2/min per mg. Thromboxane synthase retained 75-90% of its enzymic activity when bound to phenyl-Sepharose. The immobilized enzyme was inactivated at pH 3.0 and inhibited by 1-benzylimidazole and U-63,557A. The ability of the enzyme to produce thromboxane A2 from prostaglandin H2 was dramatically reduced by multiple additions of prostaglandin H2. Our data suggest that the production of thromboxane A2 by the enzyme is self-limiting and that the enzyme is inactivated during the reaction.

The asymmetric distribution of phospholipids in bovine endothelial-cell membranes was probed with 2,4,6-trinitrobenzenesulphonate and purified phospholipase A2. The data suggest that phosphotidylethanolamine is primarily located in the inner lipid bilayer, as reported for other cell types. Stearic acid is taken up by the endothelial cells and is randomly distributed among the membrane phospholipids. In contrast, the polyunsaturated fatty acids (arachidonic, eicosatrienoic and eicosapentaenoic acids) have initial incorporation into the phosphatidylcholine fraction. These fatty acids then undergo a time-dependent transfer from phosphatidylcholine to phosphatidylethanolamine. Thus we propose that endothelial cells possess a mechanism for the selective internalization of polyunsaturated fatty acids.

A cone and plate viscometer and Coulter Counter were used to study platelet modulation of polymorphonuclear leukocyte (PMNL) aggregation caused by controlled shear stress. As an index of aggregation, the large-particle percentage (LPP) was calculated. This represents the ratio of aggregated cell count to total cell count. PMNL suspensions in buffer (1.0 X 10(7) cells per milliliter, final concentration) did not show any aggregate formation at shear stresses below 150 dynes/cm2 for one minute exposure time (LPP less than 3%). However, there was PMNL aggregation in mixed PMNL and platelet-rich plasma suspensions in this shear stress range. Supernatant plasma from sheared platelets initiated PMNL aggregation at moderate shear stress (150 dynes/cm2 for one minute; LPP, 20.3% +/- 2.5%). In contrast, platelet release factors, such as adenosine diphosphate (2 mumol/L) and serotonin (2 mumol/L) did not cause PMNL aggregation (LPP, 2.9% +/- 1.2% and 3.3% +/- 0.8%, respectively). The use of a cyclo-oxygenase inhibitor (acetylsalicylic acid, 50 mumol/L) did not suppress the aggregation of PMNLs after shear (LPP, 20.1% +/- 2.4%). However, preincubation with nordihydroguaiaretic acid (10 mumol/L), an inhibitor of C-5 and C-12 lipoxygenase, and 6,9- deepoxy-6,9-(phenylimino)-6,8-prostaglandin I1 (U-60257, 10 mumol/L), an inhibitor of C-5 lipoxygenase in human leukocytes, suppressed this aggregation (LPP, 9.1% +/- 2.5% and 10.4% +/- 3.2%, respectively). Also, the formation of lipoxygenase products (5-HETE, 12-HETE, 15-HETE, and LTB4) activated by shear stress was documented by reversed phase- high-performance liquid chromatography (RP-HPLC). These data support the possibility of a cooperation between platelets and leukocytes in shear-induced PMNL aggregation that is dependent on C-12 or C-5 lipoxygenase activity, or both.

Thromboxane synthase has been immobilized on phenyl-Sepharose beads by adsorption. The immobilized enzyme is catalytically active and has a slightly lower apparent Km for PGH2 than the detergent-solubilized enzyme. However, both imidazole- and pyridine-based inhibitors are equally effective in inhibiting the immobilized and solubilized enzyme preparations. Although the immobilized enzyme appears to be less stable than the solubilized enzyme it is sufficiently stable to be used as a model for studying the properties of the enzyme.

Permeability coefficients of human umbilical vein endothelial cell monolayers cultured on polycarbonate filters were determined by monitoring transendothelial albumin transport. Permeability was determined as a function of time in culture and in the presence of vasoactive agonists. Permeability decreased with increasing time in culture. All agonist experiments were performed with 15-day cultures because this time point best modeled the in vivo permeability barrier function. Permeability of endothelial monolayers decreased significantly in the presence of the stable prostacyclin analogue iloprost (6 nM), dibutyryl adenosine 3′,5′-cyclic monophosphate (cAMP, 0.5 mM)-3-isobutyl-1-methylxanthine (IBMX, 0.1 mM), 8-bromo cAMP (0.5 mM)-IBMX, dibutyryl cAMP-theophylline (0.5 mM), or IBMX. A 9.6-fold increase in permeability resulting from thrombin [0.15 U/ml (1 nM)] treatment was inhibited by pretreating the monolayers with dibutyryl cAMP-IBMX, 8-bromo cAMP-IBMX, dibutyryl cAMP-theophylline, dibutyryl cAMP, IBMX, iloprost, or D-Phe-Pro-Arg-CH2-alpha-thrombin (1 nM). The thrombin-induced permeability increase was not significantly altered by pretreating monolayers with aspirin (5 microM) or indomethacin (50 microM). Inactivated forms of thrombin, diisopropylflurophosphate-alpha-thrombin (1 nM) and D-Phe-Pro-Arg-CH2-alpha-thrombin, did not significantly affect permeability. Monolayer permeability was not altered in response to bradykinin (1 microM). These results suggest a mediating role for intracellular cAMP in the permeability barrier function of endothelial monolayers.

Monoclonal antibodies to thromboxane B2 (TXB2) have been produced and characterized. Both liquid and solid phase radioimmunoassays have been developed using one of these monoclonal antibodies. The two assays gave similar results when used to quantitate TXB2 in 11 serum samples; however the solid phase assay was more sensitive than the liquid phase assay (i.e., 63 pg/ml vs 19 pg/ml) at a B/BO = 90%). Despite a difference in the sensitivity of the two assay systems, the cross-reactivity of the monoclonal antibody for PGD2, PGE2, PGF2 alpha and 6 keto-PGF1 alpha was the same.

A fractionation procedure has been developed which permits the isolation of 1 to 2 mg of homarine from a single shrimp. This procedure was used to show that homarine is endogenously synthesized by Penaeus duorarum in the free unbound form, and to study the metabolic precursors involved. Injected DL-[14C]tryptophan was not converted to [14C]homarine. However, [6-14C]quinolinic acid, a known catabolite of tryptophan, is an effective precursor. [2-14C]Acetate and [U-14C]glycerol are effectively converted to [14C]homarine while [14C]bicarbonate is poorly utilized. The injection of L-[U-14C]aspartate resulted in labeled homarine, but the quantity converted was less than expected. Since [14C]glycerol is an effective precursor there is a possibility that quinolinic acid may be formed in P. duorarum by a condensation similar to that of glyceraldehyde 3-phosphate with aspartic acid or a closely related metabolite. It is suggested that decarboxylation of quinolinic acid gives rise to picolinic acid which is methylated to yield homarine. L-[methyl-14C]Methionine efficiently provides the N-methyl carbon presumably via S-adenosylmethionine.

A pilot scale HYBRID reactor was operated under steady state and dynamic conditions using a pulp and paper mill effluent as a feedstock. Data collected during experimentation on the pilot plant were used to evaluate two different mechanistic dynamic models of the process. Results showed that both models were adequate in qualitatively describing steady state and dynamic process behaviour but would be of limited use in directly providing estimates of process variables for control purposes.

To determine whether accelerated degradation of PGI2 plays a role in thrombosis, we investigated the kinetics of plasma PGI2 breakdown in 7 normal subjects and 3 patients with small vessel thrombosis (2 with thrombotic thrombocytopenic purpura and one with idiopathic thrombotic stroke). Plasma PGI2 degradation was evaluated by incubating standard PGI2 with plasma at 37°C and measuring the PGI2 activity remaining at serial time intervals. PGI2 activity was determined by its capacity to inhibit platelet aggregation, and its hydrolysis product, 6-keto-PGF1α , was measured by radioimmunoassay. Plasma PGI2 survival time of all 3 patients was significantly shorter (

Cerebral ischemia and infarction result from impaired perfusion of brain tissue. Cellular homeostasis is disrupted by a variety of factors, one of which is deacylation of phospholipid membranes resulting in generation of arachidonic acid (AA) and its proaggregatory and vasoconstrictive metabolites, prostaglandin H2 (PGH2) and thromboxane A2 (TXA2). Our interest in AA metabolism in cerebral ischemia has developed from our studies of platelet-vessel wall interactions in the deendothelialized rabbit aorta. We have used this model, along with in vitro studies of platelet aggregation, to investigate pharmacological inhibition of AA metabolism. This paper will review our earlier work and give the results of experiments using 1-benzylimidazole (1-BI), a selective inhibitor of thromboxane synthase, in a rat model of transient forebrain ischemia.

Pathological conditions such as ischemia or postischemic recirculation stimulate the activity of cellular phospholipases, resulting in the release of arachidonic acid (AA) from membrane phospholipids [10, 13]. AA serves as the precursor for several biologically active substances, including prostaglandins and leukotrienes. The accumulation of these AA metabolites in cerebral tissue is believed to promote inflammation, edema formation, and decrease in blood flow.

A comparative analysis of prostaglandin production was carried out on human promyelocytic leukemia (HL-60) cells treated with either PMA or DMSO. When incubated with [1-14C]arachidonic acid these cells produced significant amounts of 6-keto prostaglandin F1 alpha, thromboxane B2, prostaglandin F2 alpha, prostaglandin E2, prostaglandin D2 and 12-hydroxy-5,8,10-heptadecatrienoic acid via the cyclooxygenase pathway. The major cyclooxygenase metabolite synthesized by these cells was prostaglandin F2 alpha. Its production increased significantly when the HL-60 cells were treated with PMA and decreased when treated with DMSO as compared to untreated control cells. This change in the production of prostaglandin F2 alpha appears to reflect alterations in cyclooxygenase activity. Another unidentified arachidonic acid metabolite was routinely observed in C18 high pressure liquid chromatography. The synthesis of this compound was inhibited by indomethacin. The unidentified metabolite was also seen in the human macrophage-like cell line U937.

The uptake and metabolism of arachidonic acid (AA) by human umbilical vein endothelial cells was studied for cells in stationary culture and for cells exposed to physiological levels of shear stress. For cells grown in stationary culture, the initial incorporation of arachidonic acid was primarily into diacylglycerol and phospholipids. Cells exposed to flow incorporated labeled arachidonic acid at a similar rate as cells maintained in stationary culture; however, the distribution of the label was altered by flow. The incorporation of arachidonic acid into diacylglycerol and phosphatidylinositol was increased in cells exposed to flow. The largest increase occurred for cells exposed to arterial levels of shear stress for the shortest time period studied, 0.5 h. Prostacyclin (PGI2) and PGF2 alpha were the principal arachidonic acid metabolites formed. Shear stress-stimulated cells preferentially produced PGI2 relative to other eicosanoid products. The initiation of flow caused a burst of AA metabolism which was highly specific for PGI2. This might represent an increase in the turnover of phosphatidylinositol-bound arachidonic acid which is specifically converted to PGI2 as a result of flow-induced membrane stresses.

Renal carcinoma in male Syrian hamsters, induced by chronic administration of estradiol for 5-7 months, is known to arise in the cortex at the cortico-medullary junction. In this in vivo model for hormonal carcinogenesis, estrogen-induced covalent DNA adducts have previously been observed in whole kidney and have been postulated to be involved in tumor induction. In the present study, the intrarenal distribution of estrogen-induced DNA modification and estrogen metabolizing enzymes were investigated in male Syrian hamsters to ascertain a role of metabolism and adduct formation in estrogen-induced carcinogenesis. The highest estrogen-induced DNA adduct concentrations as measured by 32P-postlabeling analysis were found in the renal cortex of hamsters treated with estradiol for 7 months. Total adduct levels in medullary DNA were approximately one-half of those found in cortex. Cytochrome P-450 enzymes were detected only in microsomes of kidney cortex (approximately 0.8 +/- 0.6 nmol P-450/mg protein) but not medulla of untreated male Syrian hamsters. Prostaglandin endoperoxide synthase activity in kidney cortical microsomes was 1/5 of the activity found in medullary microsomes. Thus, microsomal cytochrome P-450 levels and estrogen-induced DNA adduct formation were highest in hamster kidney cortex, the origin of renal tumorigenesis. It is postulated that estrogen metabolism by cytochrome P-450 enzymes leading to covalent DNA modification plays a role in hormonal carcinogenesis in the hamster kidney.

It is well recognized that thromboxane A2(TXA2) plays an important role in platelet reactivity. To determine the role of TXA2 in platelet-vessel wall (P-V) interaction, the effect of 1-benzylimidazole (1-BI), a specific inhibitor of thromboxane synthetase, and 13-azaprostanoic acid (APA), a TXA2 antagonist, on platelet thrombus formation was evaluated in vivo in NZW male rabbits using the autologous indium-111 (111In) labeled platelet technique. Rabbits were treated with intravenous 1-BI or APA or vehicles. After injection of autologous 111In-platelets, de-endothelialization of the abdominal aorta was created by a balloon catheter technique. At 3 hrs, blood samples were obtained and the animals were sacrificed. The aortae were removed and the injured and uninjured segments were dissected. Radioactivity counts and dry weight of the tissues and blood were determined. The vascular radioactivity counts were converted to platelet numbers by using a standard linear calibration curve. As small numbers of platelets adhered to normal vessel wall nonspecifically, this number was subtracted to obtain specific platelet accumulation at the injured sites. 1-BI at 10mg/kg reduced the specific platelet accumulation significantly (n=5, 12.3±S.D.I.5×106 pl/gm tissue; p