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ω-Transaminases ATA-40, ATA-47 and ATA-82P were coated with room-temperature solid phase ionic liquids (RTSPILs) by means of three methods, melt coating, precipitation coating, and co‐lyophilization, and showed increased stability in all of the five tested organic solvents. Co‐lyophilization and melt coating were further found to have an activating effect on the enzymes. The former led to an up to 8‐fold increase of reaction rate and excellent recyclability. The coating also protected the cofactor pyridoxal 5′‐phosphate (PLP), which is essential for transaminase activity, from degradation, leading to a reaction proceeding for 27 days. With this method the sparingly water soluble substrate 5‐bromo-1-indenone could be processed enzymatically in cyclohexane as solvent.

Kinetic promoter that enhance the reaction kinetics with CO2 are enabling the use of the low heat of reaction of slow absorbing solvents like MDEA. Mass transfer experiments with 30 wt% MDEA promoted by either by 1.7 and 8.5 g/L enzyme carbonic anhydrase (CA) or 5 wt% piperazine (PZ) where conducted in a wetted wall column apparatus at 298, 313 K and 328 for different solvent loadings. The mass transfer of PZ promoted solvents was strongly influenced by the solvent loading as it was steeply decreasing for all temperatures; the temperature was also influencing the mass transfer, but the extent was dependent on the solvent loading. CA promoted solvent mass transfer characteristics showed less dependency on the solvent loading and temperature. Lower enzyme concentrations were found to be much slower than MDEA/PZ solvents, whereas high enzyme concentrations might be as efficient in capturing CO2 as a 30 wt% MDEA/5 wt%PZ mixture in terms of overall mass transfer, considering change of mass transfer due to solvent loading over the height of a column.

In this study the effect of carbonic anhydrase addition on the absorption of CO2 was investigated in a wetted wall column apparatus. Four different solvents: the primary amine monoethanolamine (MEA), the sterically hindered primary amine 2-amino-2-methyl-1-propanol (AMP), the tertiary amine N-methyl-diethanolamine (MDEA) and the carbonate salt solution K2CO3 were compared in concentrations from 5 to 50 wt% in a temperature range of 298–328 K with and without enzyme. Necessary mass transfer parameters such as liquid side mass transfer coefficient and solvent and enzyme reaction rates were determined and benchmarked to a 30 wt% MEA solution. The study reveals that the addition of the enzyme carbonic anhydrase (CA) dramatically increases the liquid side mass transfer coefficient for MDEA, and K2CO3; AMP has a moderate increase whereas MEA was unchanged. The results confirm that just bicarbonate forming systems benefit from CA. The influence of temperature on the enzyme kinetics and mass transfer coefficients is different for different solvent types. A temperature increase resulted in lower liquid side mass transfer coefficient for MDEA and K2CO3 but in a higher coefficient for AMP. The overall first order enzyme reaction rate (s−1) was linearly dependent on enzyme concentration for MDEA and K2CO3 at 313 K. Temperature and concentration did increase the enzymatic rate constant slightly in the concentration range of 5–15 wt% K2CO3 and significantly between 15 and 20 wt%. The enzymatic reaction rate constant for MDEA decreased with temperature, the solvent concentration had a negligible on it. The enzymatic reaction rate for AMP rose with temperature and was higher for lower solvent concentration.

A stepwise selection procedure is presented to quickly evaluate whether a given ω-transaminase reaction is suitable for a so-called “simple” scale-up for fast industrial implementation. Here “simple” is defined as a system without the need for extensive process development or specialized equipment. The procedure may be used when investment in intensive process development cannot be justified or when rapid execution is paramount, for applications such as small singular batches. The three-step evaluation procedure consists of: (1) thermodynamic assessment, (2) biocatalyst activity screening, and (3) determination of product inhibition. The method is exemplified with experimental work focused on two products: 1-(4-bromophenyl)ethylamine and (S)-(+)-3-amino-1-Boc-piperidine, synthesized from their corresponding pro-chiral ketones each with two alternative amine donors, propan-2-amine, and 1-phenylethylamine. Each step of the method has a threshold value, which must be surpassed to allow “simple” implementatio...

In this study a CO2 mass transfer model was developed for carbonic anhydrase-enhanced MDEA solutions based on a mechanistic kinetic enzyme model. Four different enzyme models were compared in their ability to predict the liquid side mass transfer coefficient at temperatures in the range of 298 to 328 K, solvent concentrations in the range 15 to 50 wt%, CO2 partial pressures up to 50 kPa, solvent loading between 0 and 0.5 mole CO2 per mole MDEA and enzyme concentrations up to 8.5 g/L. The reversible Michaelis Menten model (MR) and the simplified model with product inhibition by the bicarbonate ion (SP) were able to predict the mass transfer with an absolute average relative deviation of less than 15%. The MR model could account for every influence (solvent concentration, temperature, solvent loading, CO2 partial pressure) of the different process conditions on the mass transfer, whereas the SP model is limited to applications with low CO2 partial pressure such as CCS from coal burning power plants. Two other models that were also investigated are not suitable for implementation into an absorber column simulation, as they cannot describe the influence of changing solvent loading on the mass transfer.

A simple, easy-to-use, and fast approach method is proposed and validated that can predict whether a transaminase reaction is thermodynamically unfavourable. This allowed us to deselect, in the present case, at least 50% of the reactions because they were thermodynamically unfavourable as confirmed by experiment. Once a larger data base is established, in silico screening of several new reactions (new target molecules) can easily be performed each day.

In recent years biocatalytic transamination using ω-transaminase has become established as one of the most interesting routes to synthesize chiral amines with a high enantiomeric purity, especially in the pharmaceutical sector where the demand for such compounds is high. Nevertheless, one limitation for successful implementation and scale-up is that the thermodynamics of such conversions are frequently found unfavourable. Herein we report experimental measurements of apparent equilibrium constants for several industrially relevant transamination reactions in a systematic manner to better understand the effect of amine acceptor and donor choice. For example, we have found that ortho-substitution of acetophenone like molecules, had a significant impact on the thermodynamic equilibrium. Likewise, the effect of cyclic amine acceptors was evaluated and compared to similar non-cyclic structures. It was found that an aliphatic six membered ring was favourable and a conjugated bicyclic five membered ring structure, unfavourable. Finally, we evaluated and compared the use of five different donor molecules, and calculated their ΔGapp values. This is particularly important in the further implementation of such reactions because it may be used to help select suitable donor/acceptor combinations. The results presented here give guidance, with respect to thermodynamics, in order to further extend the application of biocatalytic transamination.

As a long-lived, late-maturing species, lake sturgeon Acipenser fulvescens are vulnerable to the bioaccumulation of contaminants, which may impact reproductive physiology. The purpose of this study was to use a nondestructive method to investigate the relationship between endocrine-disrupting contaminants and sex steroids in lake sturgeon from the lower Niagara River. We screened blood plasma samples from lower Niagara River lake sturgeon (n = 63) during April and May of 2012 for concentrations of 17 organochlorine (OC) contaminants that may affect endocrine function, as well as for abnormal levels of sex steroids testosterone (T) and 17β-estradiol (E2). We found detectable levels of two OC contaminants in the blood plasma of lake sturgeon, DDE (n = 21) and γ-BHC (n = 1). In both cases, plasma contaminant concentration was well below levels known to adversely affect sturgeon reproductive physiology. In addition, qualitative analysis of chromatographs from plasma extracts did not show the presence of other peaks that matched polychlorinated biphenyl standard peaks. Comparisons of plasma steroid levels with those of others from the literature gave no indication of endocrine disruption, though plasma T levels were notably high in the lower Niagara River population. We conclude that plasma OC levels are below threshold levels found in the scientific literature that would affect lake sturgeon reproductive physiology, and that it is unlikely that significant contaminant-mediated endocrine disruption is occurring in this population.

The great importance of amide bonds in industrial synthesis has encouraged the search for efficient catalysts of amide bond formation. Microbial transglutaminase (MTG) is heavily utilized in crosslinking proteins in the food and textile industries, where the side chain of a glutamine reacts with the side chain of a lysine, forming a secondary amide bond. Long alkylamines carrying diverse chemical entities can substitute for lysine as acyl-acceptor substrates, to link molecules of interest onto peptides or proteins. Here, we explore short and chemically varied acyl-acceptor substrates, to better understand the nature of nonnatural substrates that are tolerated by MTG, with the aim of diversifying biocatalytic applications of MTG. We show, for the first time, that very short-chain alkyl-based amino acids such as glycine can serve as acceptor substrates. The esterified α-amino acids Thr, Ser, Cys, and Trp--but not Ile--also showed reactivity. Extending the search to nonnatural compounds, a ring near the amine group--particularly if aromatic--was beneficial for reactivity, although ring substituents reduced reactivity. Overall, amines attached to a less hindered carbon increased reactivity. Importantly, very small amines carrying either the electron-rich azide or the alkyne groups required for click chemistry were highly reactive as acyl-acceptor substrates, providing a robust route to minimally modified, "clickable" peptides. These results demonstrate that MTG is tolerant to a variety of chemically varied natural and nonnatural acyl-acceptor substrates, which broadens the scope for modification of Gln-containing peptides and proteins.

The San Francisco Estuary (SFE) is heavily influenced by anthropogenic activities, including historic and chronic contaminant inputs. These contaminants can adversely affect SFE fish populations, particularly white sturgeon, because they are a benthic dwelling, long-lived species. We measured a suite of metals and organic contaminants in liver and gonad tissues of 25 male and 32 female white sturgeon as well as several physiological indicators of sturgeon health. Most sturgeon (68% of males and 83% of females) were estimated to be between 13 and 17 years of age. Sturgeon tissues had elevated concentrations of several metals, including As, Ba, Cd, Cu, Cr, Pb, Hg, Ni, Se, and Zn. The most frequently detected organic contaminants in sturgeon livers and gonads were DDE, PCBs, PBDEs, and galaxolide. Selenium was detected at levels similar to those shown to cause impaired liver physiology and reproductive success in white sturgeon. Observed Hg levels were higher than those shown to result in lower condition factor and gonadosomatic indices in white sturgeon. Liver galaxolide levels correlated with decreased plasma estradiol levels in female sturgeon. The Cd, As, and Cu warrant further investigation, because they were detected at levels known to impair fish health. Our results suggest contaminants are negatively affecting SFE white sturgeon health and fitness. Future SFE white sturgeon contaminant research is suggested.

The pattern of feeding of Eastern spruce budworm Choristoneura fumiferana (Clem.) (Lepidoptera, Tortricidae) is compared on foliage from white spruce Picea glauca (Moench) Voss. (Pinaceae) trees previously determined to be susceptible and resistant to defoliation by budworm. No differences are observed in electrophysiological responses from taste sensilla to aqueous extracts of the two foliage types, nor is there a preference for either extract type in a choice test. Acetone extracts from the two foliage types are both preferred to a control sucrose solution, although neither elicits a preference relative to the other. These results suggest that there is no difference in phagostimulatory power of internal leaf contents of the two foliage types. Longer-term observation of feeding behaviour in a no-choice situation shows no difference in meal duration, confirming the lack of difference in phagostimulatory power. However, on average, intermeal intervals are twice as long on the resistant foliage, leading to an overall lower food consumption during the assay. This result suggests an anti-digestive or toxic effect of the resistant foliage that slows behaviour and limits food intake. Previous research has shown that waxes of the resistant foliage deter initiation of feeding by the spruce budworm and that this foliage contains higher levels of tannins and monoterpenes. The data suggest that the resistant foliage contains a post-ingestive second line of defence against the spruce budworm.

We analyzed white muscle samples from six species of Antarctic fish (suborder Notothenioidei) collected in 2011 from McMurdo Sound, Ross Sea, Antarctica, to assess levels of total mercury (THg). Gymnodraco acuticeps and Trematomus bernacchii exhibited the highest concentrations of THg followed by Trematomus pennellii, Trematomus nicolai, Trematomus newnesi and Pagothenia borchgrevinki, (71.3, 53.9±32.1, 45.8±27.3, 37.2±18.6, 35.7±23.6, and 21.9±2.8 ng/g wet weight, respectively). The results from this study suggest that THg has the potential to bioaccumulate from various marine Antarctic ecosystems into biota.

‘Systems Biocatalysis’ is a term describing multi-enzyme processes in vitro for the synthesis of chemical products. Unlike in-vivo systems, such an artificial metabolism can be controlled in a highly efficient way in order to achieve a sufficiently favourable conversion for a given target product on the basis of kinetics. However, many of the most interesting non-natural chemical reactions which could potentially be catalysed by enzymes, are thermodynamically unfavourable and are thus limited by the equilibrium position of the reaction. A good example is the enzyme ω-transaminase, which catalyses the transamination of a pro-chiral ketone into a chiral amine (interesting in many pharmaceutical applications). Here, the products are often less energetically stable than the reactants, meaning that the reaction may be thermodynamically unfavourable. As in nature, such thermodynamically-challenged reactions can be altered by coupling with other reactions. For instance, in the case of ω-transaminase, such a coupling could be with alanine dehydrogenase. Herein, the aim of this work is to identify thermodynamic bottlenecks within a multi-enzyme process, using group contribution method to calculate the Gibbs free energy change, Δ G r o ′ , of the overall cascade. The findings show that unfavourable reactions in the cascade can be improved by coupling to a favourable reaction giving more energetically stable products.

A new measurement method, called SeCaP, has been used to measure the water content in oil/water dispersions. The measuring principle is based on an oscillator working at approximately 20 MHz. The dielectric property of the medium adjacent to one single free electrode affects the frequency of the oscillator. The dispersion was produced by means of recirculation through a colloid mill. The concentration of water was first increased from zero to approximately 70%. Then, it was reduced from 100% to approximately 45%. The probe signal correlates very well with the water concentration in the dispersion, especially for the oil continuous case with a correlation coefficient of 0.9998. The instrument represents a new approach of measuring the water content in process streams in, for example, oil production facilities, where it is important to have reliable information on the amount of water that is flowing in the production tubing.

Here, we have investigated if targeting of T cell epitopes to chemokine receptors results in improved CD4+ T cell responses. Mouse monoclonal antibodies (mAb) with kappaL chains were targeted to various chemokine receptors expressed on human monocytes or immature dendritic cells (DC), and proliferation of cloned human, DR4-restricted CD4+ T cells specific for mouse Ckappa(40-48) was measured. When using monocytes as antigen-presenting cells, mAb specific for CCR1, CCR2, CCR5, and CXCR4 were 100-10,000-fold more efficient at inducing T cell proliferation when compared to isotype-matched control mAb on a per molecule basis. Targeting of immature DC was less effective and was only seen with anti-CCR1 and anti-CXCR4 mAb. Anti-chemokine receptors mAb required to be processed by the conventional endosomal MHC class II presentation pathway. The mAb did not induce signaling through the chemokine receptors as they failed to induce mobilization of cytosolic Ca2+ and actin polymerization. They also failed to induce APC maturation. The results strongly suggest that chemokine receptors channel antigen into the endocytic pathway for presentation on MHC class II molecules. Targeting T cell epitopes to chemokine receptors by recombinant antibody should be a useful vaccine strategy for the induction of strong CD4+ T cell responses.

We evaluated the effect of short-term exposures to a xenobiotic chemical during early life-history stages on the long-term immune competence of chinook salmon (Oncoryhnchus tshawytscha). Immersion of chinook salmon eggs in a nominal concentration of o,p-dichlorodiphenyldichloroethylene (o,p-DDE; 10 ppm) for 1 hr at fertilization followed by immersion in the same dose for 2 hr at hatch resulted in a significant reduction in the ability of splenic leukocytes from fish 1 year after treatment to undergo blastogenesis upon in vitro stimulation with lipopolysaccharide. We also observed that the vehicle, dimethyl sulfoxide (DMSO), caused a significant reduction in the ability of the splenic leukocytes to express surface immunoglobin M (SIgM) at this time. The concentration of o,p-DDE in a pooled sample of whole fry from this treatment was 0.53 microg/g lipid 1 month after first feeding but was undetectable in all other treatments. Mortality rate, time to hatch, fish length, and weight were unaffected by treatment with o,p-DDE. Similarly, sex ratios, gonadal development, and concentrations of plasma estradiol and 11-ketotestosterone were not affected by the treatment. In addition, we found no evidence that plasma lysozyme concentrations or the mitogenic responses of splenic leukocytes to concanavalin A or polyinosinic-polycytidylic acid were influenced by the treatment. In this experiment, a brief period of exposure to o,p-DDE or DMSO during early development was able to induce long-term effects on humoral immune competence of chinook salmon. Such immunosuppression may increase susceptibility to disease, which may in turn be critical to regulating the population.

†Environmental Science Program, Pacific University, 2043 College Way, Forrest Grove, Oregon 97116, USA‡Aquaculture Research Center, Kentucky State University, Frankfort, Kentucky 40601, USA§U.S. Fish and Wildlife Service, Rock Island Field Office, 4469 48th Avenue Court, Rock Island, Illinois 61201zzNational Fish Health Laboratory, U.S. Geological Survey, Biochemical Resources Division, Leetown Science Center,Kearneyville, West Virginia 25430(Received 29 July 1999; Accepted 27 January 2000)Abstract—Fifty paddlefish (Polyodon spathula) collected from two sites on the Ohio River and from one site on the CumberlandRiver, USA, were examined to determine gonad polychlorinated biphenyl (PCB) and chlordane concentrations, amounts of plasmasex steroids (testosterone and estradiol), hepatic microsomal ethoxyresorufin-O-deethylase (EROD) activity, and the presence ofimmunoreactive cytochrome P450 1A (CYP1A) protein. Percent hatch and liver, spleen, and kidney histology were also determined.Gonad PCB and chlordane concentrations were significantly higher in Ohio River paddlefish than in Cumberland River paddlefish.Gonad PCB and chlordane concentration and gonad percent lipid were correlated in Ohio River paddlefish. Five of 10 Ohio Riveregg samples exceeded the Food and Drug Administration’s action limit for chlordane (0.30mg/g). Polychlorinatedbiphenylcongener-specific analysis detected predominantly the tetra-, penta-, and hexachlorobiphenyls in paddlefish testes. Plasma testosterone levelswere significantly lower in males collected from the upper Ohio River site than those collected from the lower part of the river.There was no measurable hepatic microsomal EROD activity in any of the 50 paddlefish collected from the three sites. Westernblotting analysis confirmed that a rabbit antitrout CYP1A1 IgG antibody did not recognize a CYP1A protein in paddlefish livermicrosomes. Percent hatch was not significantly different in eggs collected from the Cumberland (88–96%) and Ohio Rivers (90–95%). Histological analysis of liver, spleen, and kidney detected the presence of hepatic steatosis and hemosiderosis, spleniclymphoid cell depletion, and hyperplasia of interrenal and chromaffin tissues. Immunosuppression, hepatic metabolic disorders, andaltered neuroendocrine function may be occurring in Ohio River paddlefish. Results presented here suggest that organochlorineexposure may be jeopardizing the long-term health of Ohio River paddlefish and that additional investigation of contaminant effectson immune system function and hormone levels in paddlefish is warranted.Keywords—Paddlefish Polychlorinated biphenyls Chlordane Reproduction BiomarkersINTRODUCTION

BACKGROUND: Metoprolol can improve haemodynamics in chronic heart failure, but survival benefit has not been proven. We investigated whether metoprolol controlled release/extended release (CR/XL) once daily, in addition to standard therapy, would lower mortality in patients with decreased ejection fraction and symptoms of heart failure. METHODS: We enrolled 3991 patients with chronic heart failure in New York Heart Association (NYHA) functional class II-IV and with ejection fraction of 0.40 or less, stabilised with optimum standard therapy, in a double-blind randomised controlled study. Randomisation was preceded by a 2-week single-blind placebo run-in period. 1990 patients were randomly assigned metoprolol CR/XL 12.5 mg (NYHA III-IV) or 25.0 mg once daily (NYHA II) and 2001 were assigned placebo. The target dose was 200 mg once daily and doses were up-titrated over 8 weeks. Our primary endpoint was all-cause mortality, analysed by intention to treat. FINDINGS: The study was stopped early on the recommendation of the independent safety committee. Mean follow-up time was 1 year. All-cause mortality was lower in the metoprolol CR/XL group than in the placebo group (145 [7.2%, per patient-year of follow-up]) vs 217 deaths [11.0%], relative risk 0.66 [95% CI 0.53-0.81]; p=0.00009 or adjusted for interim analyses p=0.0062). There were fewer sudden deaths in the metoprolol CR/XL group than in the placebo group (79 vs 132, 0.59 [0.45-0.78]; p=0.0002) and deaths from worsening heart failure (30 vs 58, 0.51 [0.33-0.79]; p=0.0023). INTERPRETATION: Metoprolol CR/XL once daily in addition to optimum standard therapy improved survival. The drug was well tolerated.

Background A multicentre study permits rapid recruitment of a large number of patients. However, there is a risk of heterogeneities in end-point evaluations, as complex definitions of criteria are interpreted by several local investigators from different hospitals. Reports discussing end-point evaluation are sparse. The TRIM trial was a multicentre trial of a thrombin inhibitor in patients with unstable angina or non-Q myocardial infarction. In this study, an independent end-point committee evaluated all the reported events of death, acute myocardial infarction and refractory angina pectoris in order to obtain uniform judgements of major end-points. Study aims To describe the work of the end-point committee, to analyse its possible effect on the final study results and to discuss the impact on the design of future trials. Method The end-point committee consisted of four members, one from each participating country. After the data were processed by the study monitors, completed case record forms and patient files for patients with reported end-points were mailed to the national member of the end-point committee for judgement. The end-point committee met regularly and made final decisions about the end-points. The work of the end-point committee was documented on a separate case record form. Results The end-point committee assessed 246 events of death, acute myocardial infarction and refractory angina pectoris in 187 of the 1209 patients (15.5%) in the TRIM trial. Misinterpretation of the index event, an inclusion myocardial infarction, as an early cardiac event was found in 12 patients. After end-point committee judgements, the number of patients with acute myocardial infarction or refractory angina pectoris during 30 days of follow-up was reduced from 177 to 153 (13. 6% reduction). The classification of events was changed in 53 of 187 patients (28.3%) with death, acute myocardial infarction or refractory angina pectoris. The data assessed by the safety committee was significantly different from the final database after end-point committee judgements. Conclusion The end-point committee corrected misinterpretations in such a high proportion of cases that the final results differed significantly from the preliminary results delivered to the safety committee. End-point judgements by an end-point committee should be performed in multicentre clinical trials to improve the quality and reliability of study results.

Management of urban areas to reduce their impact on salmonids requires an understanding of the water quality affecting them, including anthropogenically derived toxic chemicals entering urban waterways used by salmonids. Toxic contaminants create complex problems for aquatic organisms and have important implications for natural resource managers. Toxicity is associated with exposure; therefore, it is important to understand the occurrence and concentration of toxic chemicals, which can range from episodic at high concentrations to chronic exposures at low concentrations. In addition, there are several categories of toxic chemicals with many individual chemicals within each class, which could have similar or very different environmental concentrations, longevity, and toxicity.

Herein we describe a novel rational approach to the design of a ω-transaminase process such that it will fulfill criteria necessary for industrial use. By first determining the fundamental properties of the reaction system, it is possible to suggest appropriate process strategies that may be used to overcome any unfavorable parameters. The ω-transaminase is used as a model system because it is an important enzyme class and developing a systematic methodology would have significant value.

Re-introduction of California Condors into Oregon is currently being considered, but there are concerns about the safety of potential food sources of this species. Condors are opportunistic feeders and a largely available food source for this species will be stranded marine mammal carcasses. We analyzed 37 blubber samples from 7 different marine mammal species collected from the Oregon and Southern Washington coasts for 18 organochlorine (OC) pesticides and 16 polychlorinated biphenyls (PCBs). Dichlorodiphenyldichloroethylene (DDE) was the most prevalent OC contaminant, making up more than 58 % of the total OC concentration measured. There were no significant differences in OC content between species or sexes.

Pharmacological therapy in cases of chronic congestive heart failure (CHF) is usually evaluated by maximal exercise time. To assess the effect of an angiotensin converting enzyme inhibitor, ramipril, 223 patients with moderate CHF were studied in 24 centres in four Nordic countries in a randomized, double-blind, placebo-controlled, parallel group design. The study drug was titrated from 1.25 mg to a maximum of 10 mg once daily (o.d) over a period of 4 weeks (mean dose 8 mg). A symptom-limited bicycle exercise test, starting at 30 watts and increasing by 10 watts.min-1, was used to evaluate exercise capacity. Reproducible tests were required at baseline, and the test was repeated after 4, 8 and 12 weeks of treatment. Seven deaths were recorded in the placebo group and one death in the ramipril group. A total of 195 patients completed 12 weeks of treatment (placebo group n = 91, ramipril group n = 104). The groups had similar baseline characteristics. Maximal exercise time was increased by mean (SD) 35 s (9) and 41 s (8) in the placebo and ramipril groups, respectively. The adjusted difference between the groups at 12 weeks was 9 s (12) (ns). A significant decrease in blood pressure and rate-pressure product at rest and at end of exercise was obtained by ramipril as compared with placebo. Significantly fewer patients deteriorated in NYHA class from baseline to 12 weeks of ramipril treatment compared to placebo (P = 0.012). Concomitant medication for CHF increased significantly in the placebo group as compared with ramipril-treated patients (P = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Juvenile rainbow trout (Oncorhynchus mykiss) were exposed for either 96 h (acute) or 16 d (subacute) to various combinations of aluminum and hardness concentrations or aluminum and humic acid concentrations between pH 7.14 and 8.58. Aluminum-induced mortality was higher at weakly alkaline pH (7.95–8.58) (attributed to up to 10-fold higher filterable aluminum concentrations) than near-neutral pH (7.14–7.64). Growth rates were higher in 16-d hardness tests at weakly alkaline pH (0.188–1.600% of initial weight∙d−1) than for fish exposed to similar aluminum concentrations at near-neutral pH (−0.535–0.756%∙d−1). This suggested that polymeric and colloidal forms of aluminum were more potent than soluble forms in restricting growth. Hardness and humic acid appeared most protective to trout against subacute aluminum toxicity. Cumulative mortality of trout exposed to 1.50 mg aluminum∙L−1at 103 or 20 mg∙L−1hardness as CaCO3was 10 and 45%, respectively. Hardness did not significantly protect against aluminum-induced growth inhibition. Trout exposed for 16 d to aluminum (0.53–2.56 mg∙L−1) and humic acid 4.31–5.23 mg∙L−1) had higher specific growth rates and decreased mortality than those exposed to aluminum and ho humic acid at any pH.

The objectives of exercise testing in congestive heart failure (CHF) may be summarized as follows: (a) detect impaired cardiac performance, (b) grade severity of cardiac failure and classify functional capability, and (c) assess effects of interventions. Several different methods are available to make these assessments, and we have to ask ourselves how well exercise testing achieves these objectives. It has to be kept in mind that the power generated by the exercising muscles is dependent on the oxygen delivery to the skeletal muscles. Oxygen uptake is the result of an integrated performance of the lungs, heart, and peripheral circulation. In patients, as well as in normal subjects, oxygen uptake is related to hemodynamic indices such as cardiac output, stroke volume, or exercise duration when a stepwise regulated maximal exercise protocol is used. However, there are major differences in the concept of a true maximum in normal subjects versus heart failure patients. Fit-normal subjects will achieve a real maximal oxygen uptake, whereas patients may stop testing before a maximum is reached because of symptoms such as dyspnea or leg fatigue. Therefore, it is better if the actual oxygen uptake can be measured. "Peak" rather than true maximal oxygen uptake has been suggested for the classification of the severity of heart failure. Peripheral factors modify the cardiac output through such factors as vascular resistance, organ function, and hormonal release. Maximal exercise will stress the cardiovascular system to a point where the weakest chain will impose a limiting effect.(ABSTRACT TRUNCATED AT 250 WORDS)

The paddlefish, Polyodon spathula, is a primitive fish characterized by a predominantly cartilaginous skeleton, a virtually scaleless body, and a rostrum or paddle nearly one-third of the body length. At the Falls of the Ohio River near Louisville, KY, paddlefish are harvested for their roe used to produce domestic caviar. The persistence of this small but intensive fishery for the roe of female paddlefish may be slowing or even reversing the recovery of populations in the Falls area of the Ohio River. Residues of toxic substances harmful to humans are being detected in many fishes in the Ohio River. Organochlorine pollutants such as chlordane and polychlorinated biphenyls (PCBs) are being detected at levels as high as those of 10 yr ago. Recent data from studies conducted in the Missouri River on PCB levels in the tissues of the shovelnose sturgeon, a species closely related to the paddlefish, indicate that the concentration of PCBs in sturgeon roe is several times that of concentrations in flesh. This study examines the PCB content of the roe of paddlefish at the location of a commercial fishery. The study investigated the partitioning of PCBs into the muscle and reproductive tissues of paddlefish, considered possible correlationsmore » between PCB concentration and age and percent lipid, and looked at the existence of any differences in mean PCB concentrations between male and female paddlefish. 17 refs., 1 fig., 1 tab.« less

Environmental security is dependent on establishing global social systems that mimic natural ecosystems and promote ecological literacy, environmental stewardship, and the equitable distribution of resources and power. The use of fossil fuels as the primary global energy source has resulted in disturbing consequences, some of which must be immediately and judiciously addressed by the global community. As leaders in the global community, institutions of higher education must abandon tradition and embrace innovation to become responsible for imparting the knowledge and skills that produce ecologically literate students. These forward-thinking institutions will embrace experiential, project-based learning practices and produce students who are environmental stewards and active citizens with a deep understanding of local ecosystems and the ways that humans can interact with them in a sustainable way. Permaculture principles have been tested and developed for over 30 years and could serve as an effective tool for teaching the concepts of sustainability in higher education. This paper describes the integration of permaculture principles into the curriculum of a small liberal arts university.

Children and adolescents in the industrial world are becoming less physically active and are adopting a sedentary lifestyle in front of computers and TV. The aim of the present investigation was to determine self-related health, physical activity, prevalence of overweight and body complaints in high school students in Norway, and to compare students in academic programs with those in vocational programs.Seven hundred and two high school students aged 16-19 years were included in the study. A questionnaire was completed in three high schools and included questions about weight and height, health, physical activity, type of physical activity/sport, intensity, possible injuries or complaints during the last three months.Twenty three percent of the students suffers from overweight/obesity are at risk of being overweight. Males reported better health than females (P0.02). Sixty-six percent of the study group reported body complaints during the last three months, a higher number of females than males (P=0.001). Students in vocational programs reported poorer self-related health than those in academic programs and the males reported better self-related health generally than females. Furthermore, there were a higher level of prevalence of overweight students in vocational programs than academic programs (P=0.039).It is important to make it easy for school children and adolescents to do physical activity at school and during leisure time in order to prevent overweight and obesity as well as chronic diseases later in life.