Tradeoffs and synergies in wetland multifunctionality: A scaling issue.

Wetland area in agricultural landscapes has been heavily reduced to gain land for crop production, but in recent years there is increased societal recognition of the negative consequences from wetland loss on nutrient retention, biodiversity and a range of other benefits to humans. The current trend is therefore to re-establish wetlands, often with an aim to achieve the simultaneous delivery of multiple ecosystem services, i.e., multifunctionality. Here we review the literature on key objectives used to motivate wetland re-establishment in temperate agricultural landscapes (provision of flow regulation, nutrient retention, climate mitigation, biodiversity conservation and cultural ecosystem services), and their relationships to environmental properties, in order to identify potential for tradeoffs and synergies concerning the development of multifunctional wetlands. Through this process, we find that there is a need for a change in scale from a focus on single wetlands to wetlandscapes (multiple neighboring wetlands including their catchments and surrounding landscape features) if multiple societal and environmental goals are to be achieved. Finally, we discuss the key factors to be considered when planning for re-establishment of wetlands that can support achievement of a wide range of objectives at the landscape scale.

In vitro models for the blood-brain barrier.

The aim of the present study was to identify a model for the blood-brain barrier based on the use of a continuous cell line, and to investigate the specificity of this model. A set of test compounds, reflecting different transport mechanisms and different degrees of permeability, as well as different physiochemical properties was selected. In vivo data for transport across the blood-brain barrier of this set of test compounds was generated as part of the study using two different in vivo models. A computational prediction model was also developed, based on 74 proprietary Pharmacia compounds, previously tested in one of the in vivo models. Molsurf descriptors were calculated and 21 descriptors were correlated with log(Brain(conc.)/Plasma(conc.)) using partial least squares projection to latent structures (PLS). However, the correlation between predicted and measured values was found to be rather low and differed between one and two log units for several of the compounds. The test compounds were analyzed in vitro using primary bovine and human brain endothelial cells co-cultured with astrocytes, and also using two different immortalized brain endothelial cell lines, one originating from rat and one from mouse. Cell models using cells not derived from the blood-brain barrier, ECV/C6, MDCK and Caco-2 cell lines, were also used. No linear correlation between in vivo and in vitro permeability was found for any of the in vitro models when all compounds were included in the analysis. The highest r2 values were seen in the bovine brain endothelial cells (r2=0.43) and MDCKwt (r2=0.46) cell models. Higher correlations were seen when only passively transported compounds were included in the analysis, bovine brain endothelial cells (r2=0.74), MDCKwt (r2=0.65) and Caco-2 (r2=0.86). By plotting in vivo Papp values against logDpH7.4 it was possible to classify compounds into four different classes: (1) compounds crossing the blood-brain barrier by passive diffusion, (2) compounds crossing the blood-brain barrier by blood-flow limited passive diffusion, (3) compounds crossing the blood-brain barrier by carrier mediated influx, and (4) compounds being actively excreted from the brain by active efflux. Papp and Pe values obtained using the different in vitro models were also plotted against logDpH7.4 and compared to the plot obtained when in vivo Papp values were used. Several of the in vitro models could distinguish between passively distributed compounds and efflux substrates. Of the cell lines included in the present study, the MDCKmdr-1 cell line gave the best separation of passively and effluxed compounds. Ratios between AUC in brain and AUC in blood were also calculated for six of the compounds and compared to ratios between Pe or Papp for transport in the apical to basolateral and basolateral to apical direction. Again the MDCKmdr-1 cell line gave the best correlation with only one compound (AZT) giving large discrepancy between in vitro and in vivo data. None of the in vitro models could identify compounds known to be substrates for carrier mediated influxed as such, and the results indicate that a tighter in vitro blood-brain barrier model probably is needed in order to facilitate studies on carrier mediated influx. The findings presented also indicate that identification of "batteries" of in vitro tests are likely to be necessary in order to improve in vitro-in vivo correlations and to make it possible to perform acceptable predictions of in vivo brain distributions from in vitro data.

Family-of-origin expressiveness: measurement, meaning, and relationship to alexithymia.

The need for research instruments to assess the impact of affective expressiveness within the family is evident, yet few appear to be adequately designed for this purpose. In this article, we present two studies addressing this need. In the first study, the original 40-item Family-of-Origin Scale was administered to 416 students to determine those items that constitute the factor structure. This instrument was designed to assess perceived levels of health in the family of origin but has unsubstantiated construct validity. Results from a confirmatory factor analysis indicated that the instrument has one major factor, and results from five other studies provide evidence supporting the construct validity. Face validity of this 22-item construct indicates that it assesses an individual's perceived level of global expressive atmosphere within his or her family of origin. In the second study, the new Family-of-Origin Expressive Atmosphere Scale and the 20-item Toronto Alexithymia Scale were administered to 295 students. Students' self-reported expressive atmospheres in their family-of-origin scores were significantly correlated with the total scores of alexithymia and each of the three factors: impaired ability to identify feelings, impaired ability to describe feelings, and externally oriented thinking processes. No significant gender differences were found.

Towards common reference intervals in clinical chemistry. An attempt at harmonization between three hospital laboratories in Skåne, Sweden.

The population sample of the Kristianstad survey, a reference intervals survey in the county of Kristianstad, was used to establish new reference intervals in clinical chemistry at the laboratories of the Central Hospital in Kristianstad, the University Hospital in Lund and the University Hospital in Mälmo. Three-hundred and fifty nine subjects, male and female, aged 20-80+ years, were invited to participate in the study, with a participation rate of 70%. Up to 70 analyses were performed on each subject, general clinical chemistry parameters in all three laboratories, specialized analyses where available. Separate a priori exclusion criteria were defined for each test. In addition, the test pattern of each individual was evaluated for signs of preclinical disease. Twelve cases of preclinical disease were discovered and clinically confirmed. Details on all test methods are presented along with information concerning instruments used, calibration procedures, methods of calculation and obtained reference intervals. Although the methods were in general calibrated against acknowledged reference materials, in some instances differences were found that made common reference intervals across all laboratories impossible. Problems relating to the practical use of international recommendations and the establishment of reliable reference intervals are discussed.

C5-substituted derivatives of 5-OMe-BPAT: synthesis and interactions with dopamine D2 and serotonin 5-HT1A receptors.

Eight new C5-substituted derivatives of the potential atypical antipsychotic agent 5-methoxy-2-[N-(2-benzamidoethyl)-N-n-propylamino]tetralin (5-OMe-BPAT, 1) have been prepared by chemical conversion of the 5-trifluoromethylsulfonyloxy (triflate) analogue 4 via various Stille-type cross-couplings, a Heck reaction, and an amidation in moderate to good yields. The 5-acetyl, 5-cyano, 5-methyl, 5-(2-furyl), 5-phenyl, methyl 5-carboxylate, and the 5-carboxamido analogues 5-11 thus obtained, the previously disclosed 5-methoxy, 5-hydroxy, and 5-unsubstituted analogues 1-3, and the 5-triflate analogue 4 were evaluated for their ability to compete for [3H]-spiperone binding to rat striatal membranes containing dopamine D2 receptors, and their ability to compete for [3H]-8-OH-DPAT binding to rat frontal cortex membranes containing serotonin 5-HT1A receptors in vitro. Compounds 1-11 displayed weak to high affinities for dopamine D2 receptors, with Ki-values ranging from 550 nM for the 5-carboxamido analogue to 4.9 nM for the 5-hydroxy analogue. The relative affinities of the 5-methoxy, 5-hydroxy, and 5-unsubstituted analogues suggested that these compounds may bind to the same site and in a similar way as the 5-oxygenated DPATs, with the 5-methoxy substituent of 1 functioning as a hydrogen bond acceptor. The serotonin 5-HT1A receptor tolerated more structural diversity at the C5-position of 1, as revealed by the higher Ki-values of 1-11, which ranged from 60 nM for the 5-carboxamido analogue to 1.0 nM for the 5-unsubstituted analogue. Partial least-squares (PLS) analysis of a set of 24 molecular descriptors, generated for each analogue, revealed no significant correlation between the dopamine D2 receptor affinities of 1-11 and their molecular properties, supporting the view that they may have different binding modes at this receptor subtype. A PLS model with moderate predictability (Q2 = 0.49) could be derived for the serotonin 5-HT1A receptor affinities of 1-11. According to the model, a relatively lipophilic, nonpolar C5-substituent should be optimal for a high affinity at this receptor subtype.

Clients' positive and negative expressiveness within their families and alexithymia.

49 prospective clients from a midwestern urban community, who sought counseling at a university training clinic, completed the Self-expressiveness in the Family Questionnaire and the 20-item Toronto Alexithymia Scale. As predicted, the positive self-expressiveness scores were significantly negatively correlated -.52 with scores on alexithymia, and the negative self-expressiveness scores were significantly positively correlated .34 with alexithymia. These results support the premise that mental health clients' self-reported lack of positive expressiveness and abundance of negative expressiveness within their family context may be attributes associated with their tendency to be alexithymic.

The increase of plasma homocysteine concentrations with age is partly due to the deterioration of renal function as determined by plasma cystatin C.

One of the main determinants of plasma homocysteine in healthy subjects is serum creatinine. In the present study, we therefore investigated the relation between plasma homocysteine concentration, serum creatinine and a new marker for glomerular filtration rate, plasma cystatin C concentration. Cystatin C reflects the glomerular filtration better than serum creatinine and is not related to the muscle mass and formation of creatinine. The study group consisted of 255 healthy subjects from a well-defined area in the southern part of Sweden. The concentration of plasma homocysteine was increased in men compared to women. This difference disappeared when men and women were stratified by serum creatinine values. Statistically significant correlations were noted between plasma homocysteine and age, plasma cystatin C and serum creatinine. It is shown that plasma homocysteine is not only correlated to serum creatinine as a result of renal function but also as a result of the relationship between homocysteine production and creatine-creatinine synthesis. Using linear regression we were able to show that plasma cystatin C had a higher explanatory value than age. Serum creatinine showed a lower explanatory power than age. The findings in the present study might suggest that the increase of plasma homocysteine concentration with age could be partly due to the deterioration of renal function.

Reference intervals for the glomerular filtration rate and cell-proliferation markers: serum cystatin C and serum beta 2-microglobulin/cystatin C-ratio.

Recent studies have indicated that serum and plasma cystatin C are better markers for glomerular filtration rate (GFR) than serum creatinine, ubiquitously used for this purpose. To fully exploit the value of serum and plasma cystatin C as GFR markers, reliable age and sex-correlated reference intervals are required. The present study comprised cystatin C determinations in plasma and sera from 259 individuals from a well-defined area in the southernmost part of Sweden. From demographic lists two men and two women were randomly selected from each one-year birth cohort above 20 years of age. No sex differences were found for plasma and serum cystatin C, whereas an increase in the cystatin C levels with age was noted, corresponding to the known age-related decrease in GFR. The following reference intervals are recommended for practical clinical use: S-Cystatin C (both sexes): 20-50 years, 0.70-1.21 mg l-1 and 50+ years, 0.84-1.55 mg l-1. The same samples were also used for determination of beta 2-microglobulin levels in order to calculate reference intervals for the beta 2-microglobulin/cystatin C-ratio, which is a more distinct marker for cell proliferation, particularly lymphoproliferation, than is the serum level of beta 2-microglobulin alone, since the ratio should be virtually uninfluenced by GFR. The beta 2-microglobulin/cystatin C-ratios were uninfluenced by sex and age and 1.45-2.43 is recommended as the serum reference interval for practical clinical use. Serum creatinine was determined in the same samples and the creatinine level was found to be strongly influenced by sex and weakly by age.

Reference intervals and decision limits for plasma lipids and lipoproteins: a practical evaluation of current recommendations.

As part of a longitudinal study--the Kristianstad Survey--we measured plasma cholesterol, HDL- and LDL-cholesterol, triglycerides and lipoprotein (a) in a reference group consisting of 203 men and women aged 20-80, randomly sampled from a well-defined area in the southernmost part of Sweden. The selection of reference individuals and the collection of specimens for assay of the constituents were performed in accordance with current recommendations. The results were subjected to statistical analyses both with and without application of exclusion criteria. Application of the theoretical exclusion criteria resulted in the exclusion of 22% of the participants; however, this procedure had a remarkably weak impact on the results: the mean values and the standard deviations were almost unaltered. The mean (standard deviation) for cholesterol was 5.9 (1.3) mmol l-1, for HDL-C 1.1 (0.3) mmol l-1, and for LDL-C 4.3 (1.2) mmol l-1. Women had higher values than men. Plasma triglycerides were positively skewed; their median and Q3-Q1-values were 1.0 and 0.5 mmol l-1 respectively, men higher than women. There was an increase with age for cholesterol and LDL-C in both sexes and for triglycerides in women. The steepest increase of cholesterol values with age in women coincided with menopause, which have a more clear-cut separation between high and low cholesterol values than did any age limit.

Evaluation of the antianginal effect of nifedipine: influence of formulation dependent pharmacokinetics.

Nifedipine capsules t.d.s. and an extended release formulation of nifedipine, nifedipine-ER tablets, given once daily in corresponding daily doses, have been compared with placebo in a double-blind, three-way cross-over study in 24 patients with stable angina pectoris. The objective was to study the influence on the antianginal effect of the different pharmacokinetics of several preparations of nifedipine. All patients received concomitant treatment with beta-adrenoceptor blockers. Antianginal efficacy was assessed by a dynamic exercise test at the end of the dosage intervals, i.e. 8 and 24 h after nifedipine capsules and nifedipine-ER, respectively, as well as 6 h after dosing. Six h after dosing the time of onset of chest pain and total exercise time were longer and total work was significantly higher during both nifedipine-ER (plasma concentration 260 nmol/l) and placebo treatment than after nifedipine capsules (plasma concentration 78 nmol/l). Time to 1 mm ST depression was longer during nifedipine-ER than during nifedipine capsule treatment. No significant difference was seen between nifedipine-ER and placebo. At the end of the dosage interval (24 and 8 h after nifedipine-ER and nifedipine capsules, respectively), no significant difference was found between nifedipine-ER (plasma concentration 75 nmol/l) and the other two treatments. However, placebo was superior to nifedipine capsules (plasma concentration 58 nmol/l) both in the time to onset of chest pain and total exercise time. The lack of effect at the end of the dosage interval was probably due to the subtherapeutic plasma nifedipine level.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunotherapy with dog and cat allergen preparations in dog-sensitive and cat-sensitive asthmatics.

Standardized dog and cat allergen preparations with defined allergen composition were used for immunotherapy (IT) in dog-sensitive and/or cat-sensitive adult patients. Seventeen patients completed 1 year of IT. Eleven patients were treated with dog allergen, five with cat allergen, and one with both dog and cat allergen. The treatment was well tolerated, with increased subjective tolerance. After 3 months of IT there was a significant decrease in conjunctival (p less than .05) and skin sensitivity (p less than .05). Specific IgE decreased significantly within 1 year as assayed by RAST and IgE-crossed radioimmunoelectrophoresis. Specific IgG increased in all patients. The results indicate that IT with potent and standardized dog and cat allergens influence the sensitivity to these allergens.

DDAVP test for renal concentration capacity. Age-related reference intervals.

The effect of different levels of fluid intake on the renal concentration test was evaluated. Maximal urinary osmolality did not significantly differ whether strict fluid restriction was kept or not. One side effect, namely headache, seemed more frequent after fluid deprivation than after a more liberal fluid intake. We suggest a practical approach to the performance of the urinary concentration test with DDAVP. The maximal urinary concentration after a single subcutaneous injection of 4 micrograms DDAVP was determined in 212 healthy adults aged 20 to 80 years. A significant decline with age was found in maximum urinary concentration, mean values ranging from 982 mOsm/kg at 20 years to 823 mOsm/kg at 80 years. References are given for different ages which render the test useful in adult patients.

Flowers and other trigger factors in asthma and rhinitis--an inquiry study.

Six hundred and eighty adult patients with asthma and/or rhinitis were questioned about symptoms elicited by 46 different flowers and 10 common non-specific environmental trigger factors listed in a questionnaire. Flowers or birch twigs were reported to elicit symptoms in 79% of the patients, somewhat more often in rhinitis than in asthma patients, and caused symptoms as often in non-atopics as in atopics. Birch twig and marguerite most frequently induced symptoms, followed by strongly smelling flowers such as hyacinth, lilac, and lily of the valley. Unspecific irritants caused symptoms in 98% of the asthmatics and in 67% of patients with rhinitis. Tobacco smoke and perfumes were the most important troublemakers. A significant positive correlation was found for elicitation of symptoms from flowers and from certain non-specific irritants. It is concluded that non-specific hyperreactivity as well as reaginic hypersensitivity are the mechanisms involved when birch twigs and flowers elicit symptoms.

Reference values for exercise tests with continuous increase in load.

Reference values for exercise tests with continuous increase in load are presented. The exercise tests were performed on an electrically braked bicycle ergometer by 188 randomly selected Swedes of both sexes who were between 20 and 79 years of age. The reference values are related to sex, age (in decades) and weight and classified in decreasing levels of exercise capacity. Reference values for systolic blood pressure at different work loads are also given.

The effects of a highly purified hyaluronidase preparation on experimental myocardial infarction in the rat.

Several substances have been claimed to be effective in reducing the area of necrosis in acute myocardial infarction. The effects of a highly purified hyaluronidase preparation (Hyalas) on experimental myocardial infarction in the rat have been evaluated in this study. In the first series, one group of rats was treated with hyaluronidase 1 500-2 000 IU/kg injected intravenously 2, 4, 18, 24, 28 and 42 hours after induction of infarction by coronary artery occlusion. Another group was treated with NaCl solution. The infarction size was evaluated by serum lactate dehydrogenase and weight of infarcted myocardium. In a second series, the substances were administered immediately after the occlusion. In this experiment, the infarction size was estimated by planimetry. The percentage of salvaged myocardium in the hyaluronidase-treated groups was within the range of 20%. It seems reasonable to suggest that the use of highly purified hyaluronidase may be of clinical value for reduction of the myocardial infarction size.

Traumatic bowing of the forearm: a case report.

In a 16-year-old girl, the forearm was caught between rollers in a textile factory. The tangential force caused massive swelling and one week later bowing of the forearm was noticed. One month and 3 months later the bowing was unchanged, and caused 30 degrees limitation of pronation while supination was normal. Bowing of the forearm bones in children following trauma, interperted as a plastic deformation of bone, is only recently recognized as a clinical and roentgenological entity.