Mobile epibenthic fauna consume organic waste from coastal fin-fish aquaculture.

Organic waste released from fin-fish aquaculture is being dispersed further as industry growth has led to the expansion of open net cages in dynamic coastal locations. Here we investigate the response of three mobile epibenthic invertebrates (brittle stars, urchins and brown crabs), whose natural habitats overlap with large scale coastal salmon farming. Using fatty acids and stable isotopes, we found these organisms displayed decreases in δ13C and δ15N and elevated levels of C18 fatty acids reflective of terrestrial components of fin-fish feeds. Furthermore, we found these three species consume aquaculture organic waste not only directly adjacent to the farm vicinity (0-20 m from cage edge) but up to 1 km away in the case of brittle stars and brown crabs. As aquaculture feeds shift to contain more terrestrial ingredients, the biochemistry of fauna feeding on organic waste is also being shifted, the result of these changes is currently unclear.

Synthesis and initial biological evaluation of new mimics of the LXR-modulator 22(S)-hydroxycholesterol.

The generic, synthetic oxysterol 22(S)-hydroxycholesterol (22SHC) has shown antagonistic effects towards liver X receptor (LXR) in vitro and promising effects on plasma triacylglycerol level and body weight-gain in animal studies. On the contrary, the endogenic LXR agonist 22(R)-hydroxycholesterol (22RHC) and synthetic LXR agonists convincingly have shown agonistic effects on genes involved in lipogenesis, and inhibitory effects on cell proliferation in vitro and in vivo. We hypothesized that the carbon side chain containing the hydroxyl group at the 22-position was a pharmacophore affecting these opposite effects on LXR. This prompted us to initiate a rational drug design incorporating the 22-hydroxylated 20-27 cholesterol moiety into cholesterol-mimicking building blocks. The two enantiomers of the 22-hydroxylated 20-27 cholesterol moiety were synthesized with an excellent enantiomeric excess and the stereochemistry are supported by X-ray crystallography. Molecular modelling of the new compounds showed promising LXR selectivity (LXRß over LXRα) and initial in vitro biological evaluation in human myotubes showed that compound 16b had agonistic effects on the gene expression of SCD1 and increased lipogenesis.

Synthesis and initial in vitro biological evaluation of two new zinc-chelating compounds: comparison with TPEN and PAC-1.

The lipophilic, cell-penetrating zinc chelator N,N,N',N',-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN, 1) and the zinc chelating procaspase-activating compound PAC-1 (2) both have been reported to induce apoptosis in various cell types. The relationship between apoptosis-inducing ability and zinc affinity (Kd), have been investigated with two new model compounds, ZnA-DPA (3) and ZnA-Pyr (4), and compared to that of TPEN and PAC-1. The zinc-chelating o-hydroxybenzylidene moiety in PAC-1 was replaced with a 2,2'-dipicoylamine (DPA) unit (ZnA-DPA, 3) and a 4-pyridoxyl unit (ZnA-Pyr, 4), rendering an order of zinc affinity TPEN>ZnA-Pyr>ZnA-DPA>PAC-1. The compounds were incubated with the rat pheochromocytoma cell line PC12 and cell death was measured in combination with ZnSO4, a caspase-3 inhibitor, or a ROS scavenger. The model compounds ZnA-DPA (3) and ZnA-Pyr (4) induced cell death at higher concentrations as compared to PAC-1 and TPEN, reflecting differences in lipophilicity and thereby cell-penetrating ability. Addition of ZnSO4 reduced cell death induced by ZnA-Pyr (4) more than for ZnA-DPA (3). The ability to induce cell death could be reversed for all compounds using a caspase-3-inhibitor, and most so for TPEN (1) and ZnA-Pyr (4). Reactive oxygen species (ROS), as monitored using dihydro-rhodamine (DHR), were involved in cell death induced by all compounds. These results indicate that the Zn-chelators ZnA-DPA (3) and ZnA-Pyr (4) exercise their apoptosis-inducing effect by mechanisms similar to TPEN (1) and PAC-1 (2), by chelation of zinc, caspase-3 activation, and ROS production.

Seasonal variation in mineralization rates (C-N-P-Si) of mussel Mytilus edulis biodeposits.

To determine seasonal variability in mineralization dynamics of mussel biodeposits, we applied a multiple-element approach measuring mineralization rates of carbon (C), nitrogen (N), phosphorus (P) and silicate (Si) during three periods (March, August and November). The results of this study showed that mineralization rates vary between seasons and between elements and that mineralization dynamics were influenced by both temperature and biodeposit nutrient composition. Mineralization rates were 3.2 ± 0.4 mmol C, 0.17 ± 0.04 mmol N, 0.06 ± 0.02 mmol P and 3.91 ± 3.75 mmol Si per gram biodeposit (DW) per day, which represented 24 % of the particulate organic C and 17 % of the particulate organic N in mussel biodeposits. Seasonal variability was largest for Si mineralization with 60-80-fold higher rates measured in March compared to August and November. This difference is most likely related to the difference in biodeposit nutrient composition. It was furthermore shown that the labile fraction of biodeposits became mineralized after, respectively, 18, 9 and 13 days during the experimental periods in March, August and November. This indicates that temperature enhances biodeposit decomposition with approximately 2-3 times faster turnover at a 10 °C temperature interval (Q10 ).

Retrospective comparison of two years in a paediatric burns unit, with and without acticoat as a standard dressing.

The Karolinska Burn Unit in Stockholm, Sweden, carried out a retrospective case review in order to compare the cost of the current protocol of care - in place since mid-2002 - with a previous protocol in paediatric burn patients. The study compared the years 2004 and 2007 with the year 2001. 2004 was the first full year in which the unit staff used Acticoat(TM) (Smith & Nephew Wound Management, Hull, England), IntraSite Gel(TM) (idem), and Allevyn Adhesive(TM) (idem) in the treatment of paediatric burns patients. In 2001 the unit used Mepitel(TM) (Molnlycke, Göteborg, Sweden) together with a saline solution and peroxide for cleansing. This study examined differences in both labour and material costs, measured from the hospital's perspective. Our results show that the main impact of the new protocol was on length of stay for hospitalized patients. In 2001 the mean in-patient stay was 12.5 days; in 2004 the mean stay was 5.6 days and, in 2007, 4.5 days (p < 0.001). It is hypothesized that the reason for this significant reduction in length of stay is that most of the patients treated with Acticoat were sent home earlier to be treated as outpatients because there was less need for sedation and/or analgesics, and because the risk of infection was perceived to be less. Pure hospitalization costs per in-patient were approximately Swedish kronor (kr) 67,725 in 2001 (1 kr = approx. € 0.1 or US$ 0.15) and kr 30,305 and kr 24,440 in 2004 and 2007, respectively. This represents a saving of 55% and 64% with respect to 2001 costs.

Population structure in a critically endangered arctic fox population: does genetics matter?

The arctic fox (Alopex lagopus) in Scandinavia is classified as critically endangered after having gone through a severe decline in population size in the beginning of the 20th century, from which it has failed to recover despite more than 65 years of protection. Arctic foxes have a high dispersal rate and often disperse over long distances, suggesting that there was probably little population differentiation within Scandinavia prior to the bottleneck. It is, however, possible that the recent decline in population size has led to a decrease in dispersal and an increase in population fragmentation. To examine this, we used 10 microsatellite loci to analyse genetic variation in 150 arctic foxes from Scandinavia and Russia. The results showed that the arctic fox in Scandinavia presently is subdivided into four populations, and that the Kola Peninsula and northwest Russia together form a large fifth population. Current dispersal between the populations seemed to be very low, but genetic variation within them was relatively high. This and the relative F(ST) values among the populations are consistent with a model of recent fragmentation within Scandinavia. Since the amount of genetic variation is high within the populations, but the populations are small and isolated, demographic stochasticity seems to pose a higher threat to the populations' persistence than inbreeding depression and low genetic variation.

Anisakiasis presenting as an obstructive duodenal tumor. A Scandinavian case.

A case of chronic anisakiasis presenting as an occluding duodenal tumor is described. Significant falls in Anisakis simplex-specific serum IgE and total IgE occurred after resection of the lesion. Histopathologic examination showed a chronic eosinophilic granulomatous infiltrate and a tubular sclerotic structure in the antral submucosa consistent with, but not diagnostic for, an A. simplex larva.

Nitric oxide indices in human septic shock.

OBJECTIVES: To study the relation between nitrite, nitrate, nitrotyrosine, and nitrosothiols as NO indices in human septic shock. DESIGN: A prospective clinical study. SETTING: Intensive care units in a university hospital and a central county hospital. PATIENTS: Sixteen patients admitted for septic shock. Nine healthy volunteers served as controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients with septic shock had a hyperdynamic circulatory response and required infusion of at least two vasopressors to maintain systemic blood pressure. Four episodes of recurrent shock occurred in two patients. Heparinized plasma was collected once daily for analysis of NO indices. Peak plasma concentrations of nitrite + nitrate (NOx) were elevated in first episodes of septic shock; 144+/-39 microM vs. controls, 20+/-3 microM (p < .05). Peak plasma NOx concentrations in recurrent shocks were; 160+/-19 microM. Peak plasma concentrations of 3-nitrotyrosine (NT) were elevated in primary septic shock 102+/-19 pmol x mL(-1) vs. controls 14+/-6 pmol x mL(-1) (p < .05). Peak NT concentrations were 117+/-37 pmol x mL(-1) in recurrent septic shock. Peak plasma NT concentrations did not coincide with peak NOx concentrations in half of the episodes of septic shock. Plasma NT was elevated (59+/-15 pmol x mL(-1) vs. controls 14+/-6 pmol x mL(-1), p < .05) in patients with normal plasma NOx concentrations throughout septic shock. Plasma concentrations of nitrosothiols did not change during septic shock. CONCLUSIONS: Plasma concentrations of NOx and NT are elevated in primary episodes of septic shock and may also be elevated in secondary septic shock, but too few episodes of recurrent septic shock occurred to allow firm conclusions. Plasma concentrations of NT are elevated in patients with septic shock with normal plasma NOx concentrations, indicating that plasma concentrations of NOx may not always accurately reflect NO production. Reactive nitrogen species may be formed in septic shock, and measuring both NOx and NT may give a better indication of NO production in septic shock than NOx alone. Plasma levels of nitrosothiols did not change during septic shock.

[Nitric oxide--basal biochemistry and physiological aspects]. / Nitrogenmonoksid--basal biokjemi og fysiologiske aspekter.

Nitric oxide (NO) is a naturally occurring molecule found in a variety of cell types and organ systems, including the cardiovascular, immune and nervous system. NO is normally produced in the endothelium from L-arginine by the constitutive isoform of the NO synthase (cNOS). Thereby, NO is an important regulator of vascular tone, prevents platelet adhesion, aggregation and activation, limits leukocyte adhesion to the endothelium and regulates myocardial contractility. This physiological production of NO is important for blood pressure regulation, blood flow distribution and tissue perfusion. Following injury or certain inflammatory stimuli, the expression of an inducible NO synthase (iNOS) can occur in a great variety of cells. In the last decade research on NO has suggested new treatment strategies for several diseases. In this review we discuss the biochemistry of NO and its basal physiological implications, with special emphasis on NO produced in the endothelium.

[Nitric oxide--an important mediator in sepsis?]. / Nitrogenmonoksid--en viktig mediator ved sepsis?

Animal experiments suggest that hyperproduction of nitric oxide (NO) by the inducible isoform of the enzyme NO synthase (iNOS) may contribute to hypotension, cardiodepression and vascular hyporeactivity in septic shock. Lipopolysaccarides and cytokines, like tumor necrosis factor, interleukin-1 and interferon-gamma, have been shown to induce iNOS in the endothelium, vascular smooth muscle cells, macrophages and different parenchymal cells. In several animal models of septic shock, treatment with inhibitors of NO synthesis has been shown to improve haemodynamic variables and survival. In human septic shock, inhibition of NO synthesis has been shown to alter haemodynamic variables in short term studies. However, a large multicentre study was recently stopped due to increased mortality in patients in septic shock treated with the NO synthase inhibitor NG-monomethyl-L-arginine. The aim of this review is to discuss the role of NO in sepsis and the potential therapeutic implications of NO as a target in treatment of human septic shock. We emphasize that many septic patients have preexisting endothelial dysfunction or lung diseases, which may predispose to severe adverse effects during systemic inhibition of NO synthesis. We also focus on the lack of direct evidence for iNOS expression in human septic shock and on the discrepancy between animal and human data.

The role of nitric oxide in sepsis--an overview.

Nitric oxide (NO) is normally produced in the endothelium by the constitutive isoform of the NO synthase. This physiological production of NO is important for blood pressure regulation and blood flow distribution. Several lines of evidence suggest that a hyperproduction of NO by the inducible form of NO synthase (iNOS) may contribute to the hypotension, cardiodepression and vascular hyporeactivity in septic shock. Lipopolysaccarides and cytokines, such as tumor necrosis factor, interleukin-1 and interferon-gamma, have been shown to induce iNOS in the endothelium, vascular smooth muscle cells, macrophages and different parenchymal cells. Treatment with inhibitors of NO synthesis has been shown to improve hemodynamic variables and survival in several animal models of septic shock. In human septic shock, inhibition of NO synthesis has been shown to alter hemodynamic variables in short-term studies, but it is uncertain whether this treatment has beneficial long-term effects. The aim of this review is to give an overview of the physiological role of NO and to discuss the role of NO in sepsis and the potential therapeutic implications of NO as a target in treatment of human septic shock. A main new aspect of this review is a critical discussion of previous reports measuring plasma nitrite/nitrate during septic shock and an evaluation of the validity of interpreting these data as evidence for a hyperproduction of NO. This review also emphasizes that many septic patients have preexisting endothelial dysfunction and lung diseases, which may contribute to adverse effects by systemic inhibition of NO synthesis. Another new aspect of the present review is a focus on the lack of direct evidence of iNOS expression in human septic shock.

N(G)-monomethyl-L-arginine improves survival in a pig model of abdominal sepsis.

OBJECTIVE: To test the effect of a continuous infusion of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) on survival rate and hemodynamics in a pig model of endogenous peritoneal live bacterial sepsis. DESIGN: Prospective, randomized trial. SETTING: Laboratory at a university medical center. SUBJECTS: Thirty-five pigs with an average weight of 26 kg (range 21 to 33). INTERVENTIONS: After surgical preparation, animals (control, n=6) given anesthesia and fluids were observed for 9 hrs. Fifteen experimental animals received 0.5 g of cecal content/kg of body weight intraperitoneally after surgery. Nine of these animals received standard anesthesia and fluids and were observed for 9 hrs or until death. Six animals received a continuous infusion of L-NMMA (10 mg/kg/hr) 3 hrs after sepsis induction. Starting 3 hrs after surgery, five nonrandomized animals were given anesthesia and fluids and received a 6-hr continuous infusion of L-NMMA (10 mg/kg/hr). An additional nine animals were anesthetized and blood samples were taken to determine plasma nitrate concentrations in nonoperated pigs. MEASUREMENTS AND MAIN RESULTS: L-NMMA treatment increased 9-hr survival in septic animals from 11% to 83% (p < .001), prevented a further decrease in mean arterial pressure and restored mean arterial pressure to control levels (p < .00002 vs. nontreated septic animals). Mean pulmonary arterial pressure increased slightly during L-NMMA infusion (p < .0003). Coronary blood flow was preserved during L-NMMA treatment. Cardiac index and urine production reached and maintained control levels during L-NMMA treatment of septic animals. Mean central venous pH did not deteriorate during L-NMMA treatment. Animals treated with L-NMMA had plasma nitrate concentrations similar to nonseptic control animals. The results from the nonseptic control group receiving L-NMMA suggest that a substantial part of the effect of L-NMMA in this model of septic shock may be due to inhibition of the constitutive nitric oxide production. CONCLUSIONS: In this porcine model of peritoneal sepsis, infusion of L-NMMA increased survival rate and maintained mean arterial pressure without worsening tissue oxygenation. Coronary blood flow, cardiac index, systemic vascular resistance, and urine production were well maintained during L-NMMA treatment.

Discrepancy between latex and ELISA D-dimer values in sepsis may be caused by human neutrophil elastase.

We have recently shown that D-dimers are degraded by human neutrophil elastase (HNE) in vitro, causing rapid decrease in the D-dimer levels measured by a Latex test, but not with an ELISA test employing the same monoclonal antibody against D-dimer. To see if such discrepant D-dimer concentrations occurred in patients with high HNE concentration, we examined 80 plasma samples from 8 patients with sepsis with a Latex and an ELISA test and calculated the ratio between the D-dimer values obtained with the two tests. Twenty healthy pregnant and twenty pre-eclamptic patients, who are known to have raised D-dimer but low HNE concentrations, were chosen as controls. HNE levels were estimated by determining the HNE-alpha 1-proteinase inhibitor complex (HNE-A1PI) concentration. HNE-A1PI concentration was increased in sepsis patients compared with pre-eclamptic patients (p < 0.0005) and healthy pregnant women (p < 0.0005). In sepsis patients, the D-dimer results were skewed towards lower ratios between Latex and ELISA values compared to pre-eclamptic patients (p = 0.008) and healthy pregnant women (p = 0.0001). In plasma samples from patients with the largest discrepancy between Latex and ELISA D-dimer values, Western blotting with immunostaining indicated degradation of D-dimers to D-like fragments similar to those observed following degradation of cross-linked fibrin by HNE in vitro. We conclude that in sepsis patients there is a marked discrepancy between Latex and ELISA D-dimer values that may be caused by HNE. In such patients Latex D-dimer assays may cause severe underestimation of fibrinolysis.

Inhibition of nitric oxide synthase does not affect survival in a rat model of abdominal sepsis.

The effect of inhibiting nitric oxide (NO) synthesis during sepsis was studied in a caecal perforation model on Wistar rats. This model induces severe abdominal sepsis with a 48-h mortality > 90% in untreated animals. The survival time in hours (median values with the 95% confidence intervals in parentheses) for the control group was 15 (11.5-27.0) h. Treatment with the inhibitors of NO synthesis, NG-monomethyl-L-arginine (LNMMA), 30 mg kg-1 body weight (BW) or S-(2-aminoethyl)-isothiourea (AET), 3 mg kg-1 BW, given either once or twice after sepsis induction did not affect survival in this model. Survival time when LNMMA was given once was 13 (11-22) h and when given twice it was 14 (8-41) h. The corresponding survival times were 9 (4-28) h and 11 (5-27) h for treatment with AET. In conclusion, this study demonstrates that survival in the present model of live multiplying bacterial sepsis is not affected by either LNMMA or AET. Testing the potential clinical effects of inhibition of NO synthesis during sepsis should not be confined to short-term studies of haemodynamic changes induced by lipopolysaccharide.

Relation of exposure to airway irritants in infancy to prevalence of bronchial hyper-responsiveness in schoolchildren.

To find out whether exposure to sulphur dioxide during infancy is related to the prevalence of bronchial hyper-responsiveness (BHR), we studied schoolchildren (aged 7-13 years) from two areas of Norway--a valley containing a sulphur-dioxide-emitting aluminium smelter and a similar but non-industrialised valley. Bronchial responsiveness was assessed in 529 of the 620 participants. The median exposures to sulphur dioxide and fluoride were 37.1 micrograms/m3 and 4.4 micrograms/m3 at ages 0-12 months and 37.9 micrograms/m3 and 4.4 micrograms/m3 at 13-36 months. The risk of BHR increased with exposure to sulphur dioxide and fluoride at these ages; the odds ratio for a 10 micrograms/m3 increase in sulphur dioxide exposure at 0-12 months was 1.62 (95% CI 1.11-2.35) and that for a 1 microgram/m3 increase in fluoride exposure was 1.35 (1.07-1.70) at 0-12 months and 1.38 (1.05-1.82) at 13-36 months. Exposure to these low concentrations of airway irritants during early childhood is associated with an increased prevalence of BHR in schoolchildren.

[Pneumocystis carinii pneumonia--not only in AIDS]. / Pneumocystis carinii-pneumoni--ikke bare ved AIDS.

Two patients with haematologic malignancies developed Pneumocystis carinii pneumonia while under outpatient treatment, one on busulphan for chronic myelogen leukemia, and the other on prednisone plus chlorambucil for non-Hodgkin's lymphoma. The first patient was moderately ill and required hospitalization for 12 days while the second patient was critically ill and needed assisted ventilation for two weeks. Eventually they both recovered and returned to work. Tests for serum antibodies to the human immunodeficiency virus (HIV) were negative in both patients. We review the problem of P. carinii pneumonia in patients receiving immunosuppressive drugs.

[Glyceryl trinitrate patches during continuous intravenous infusions]. / Glyseryltrinitratplaster ved kontinuerlige intravenøse infusjoner.

A randomized, double blind comparison of the incidence of removal of patches because of venous occlusion was performed in patients on continuous intravenous fluid therapy using 2.5 mg trinitroglycerine or placebo patches attached to the thorax. The sample comprised 90 patients, of whom nine were excluded for administrative reasons. Of the remaining 81,41 received active and 40 received placebo patches. Within one week 11 venflones occluded; ten in patients on placebo, and one in a patient with an active trinitroglycerine patch. Finally 14 (11 placebo and three trinitroglycerine) patches occluded. This tendency in favour of trinitroglycerine patches was statistically significant (p = 0.018). No difference in frequency of thrombophlebitis was observed: (14 versus 18 not leading to occlusion). Seven patients on trinitroglycerine and one on placebo developed moderate headache which did not necessitate withdrawal of treatment. It is concluded that 2.5 mg trinitroglycerine patches seem to improve survival of venflones used for continuous, intravenous fluid therapy, even when applied to the thorax.

[Cerebral hemorrhage associated with phenylpropanolamine]. / Cerebral blødning assosiert med fenylpropanolamin.

In recent years, sympathomimetic drugs, including ephedrine, amphetamine and phenylpropanolamine, have been increasingly associated with cerebral haemorrhage and infarction. We report a case of intracranial bleeding in a 37 year-old woman with mononucleosis who took therapeutic doses of phenylpropanolamine. Cerebral CT on admission showed a left-sided intracerebral hematoma. Angiography was normal. Late bleeding occurred on the fourth day. She survived but developed a right-sided cerebral infarction with persistent epilepsy. Her mononucleosis was of moderate severity without bleeding diastesis. We conclude that the intracranial bleedings were secondary to taking phenylpropanolamine.

Latent infection of epidermal Langerhans cells in HIV-positive individuals.

Epidermal cell suspensions obtained from 3 symptom-free HIV-positive individuals were cultured and marked with monoclonal antibodies for the HIV proteins p15, p24 and gp120 in the alkaline phosphatase anti-alkaline phosphatase staining technique. For 2 individuals, cells were positive after 3 days in culture, and for the third, after 4 days. Supernatant from one of the cultures infected allogeneic peripheral blood mononuclear cells. We conclude that epidermal Langerhans cells from symptom-free HIV-positive individuals are latent-infected and are able to produce and release HIV.