Impacts of atmospheric anthropogenic nitrogen on the open ocean.

Increasing quantities of atmospheric anthropogenic fixed nitrogen entering the open ocean could account for up to about a third of the ocean's external (nonrecycled) nitrogen supply and up to approximately 3% of the annual new marine biological production, approximately 0.3 petagram of carbon per year. This input could account for the production of up to approximately 1.6 teragrams of nitrous oxide (N2O) per year. Although approximately 10% of the ocean's drawdown of atmospheric anthropogenic carbon dioxide may result from this atmospheric nitrogen fertilization, leading to a decrease in radiative forcing, up to about two-thirds of this amount may be offset by the increase in N2O emissions. The effects of increasing atmospheric nitrogen deposition are expected to continue to grow in the future.

Teleradiology Uppsala-Sydney for nighttime emergencies: preliminary experience.

BACKGROUND: The development of digital imaging systems for radiology in combination with the possibility to transfer large quantities of data over the Internet has increased the interest in teleradiology. Transferring nighttime examinations to an evaluation center in a daytime zone may provide improved patient security, better working hours for radiologists, and reduced costs for emergency radiological services. PURPOSE: To evaluate the time required for transferring radiological information from Uppsala (Sweden) to Sydney (Australia). MATERIAL AND METHODS: A radiologist in Sydney reported on radiological examinations performed in Uppsala. The time required for downloading 75 examinations and returning 24 reports was registered. RESULTS: Downloading was completed in <60 min for all conventional radiological examinations, but only 44% of computed tomography (CT) examinations with >65 images. Reports were completed in <10 min. Turnaround time was directly related to the time required for downloading the images. The Sydney report was available in Uppsala within 30 min of the in-house report in 79% of examinations. CONCLUSION: The main challenge for emergency teleradiology is the time required for downloading large volumes of data over the Internet.

Renal failure in 57 925 patients undergoing coronary procedures using iso-osmolar or low-osmolar contrast media.

We compared the Swedish Coronary Angiography and Angioplasty Registry with the Swedish 'Hospital Discharge Register' to assess contrast media (CM)-induced renal failure. Hospitals used only one type CM. From 2000 to 2003, iodixanol (iso-osmolar) was used in 45 485 patients, ioxaglate (low osmolar) in 12 440 subjects. To include the earlier used CM iohexol (low osmolar), analysis extended back to 1990 (86 334 patients). Incidence of clinically significant renal failure was greatest for patients receiving the iso-osmolar CM iodixanol (1.7%). Ioxaglate-treated patients had a significantly lower renal failure incidence (0.8%, P<0.001). The odds ratio for iodixanol-treated patients was significantly higher than for ioxaglate (1 vs 0.48, P<0.001). In subsets of either diabetic patients or patients with previous renal failure, odds ratios for renal failure remained greater in the iodixanol groups (P<0.01). Hospitals switching CM to iodixanol experienced a doubling in clinically significant renal failure after cardiac procedures. Dialysis was required in 0.2% of patients receiving iodixanol, which was significantly higher (P<0.01) than for ioxaglate-treated patients (0.1%). Iohexol-treated patients had a similar low risk for developing clinically significant renal failure (0.9%) as ioxaglate. In conclusion, risk of developing renal failure and required dialysis after coronary procedures is higher when patients received iodixanol than ioxaglate or iohexol.

Global iron connections between desert dust, ocean biogeochemistry, and climate.

The environmental conditions of Earth, including the climate, are determined by physical, chemical, biological, and human interactions that transform and transport materials and energy. This is the "Earth system": a highly complex entity characterized by multiple nonlinear responses and thresholds, with linkages between disparate components. One important part of this system is the iron cycle, in which iron-containing soil dust is transported from land through the atmosphere to the oceans, affecting ocean biogeochemistry and hence having feedback effects on climate and dust production. Here we review the key components of this cycle, identifying critical uncertainties and priorities for future research.

Influence of iothalamate on renal medullary perfusion and oxygenation in the rat.

PURPOSE: To evaluate controversial results regarding the effect of the contrast medium (CM) iothalamate on renal medullary blood flow by applying two different methods simultaneously. MATERIAL AND METHODS: The outer medullary blood flow (OMBF) response was estimated using laser-Doppler flowmetry and hydrogen gas wash-out (microelectrodes) simultaneously. Outer medullary oxygen tension (PO2) was measured using Clark type microelectrodes. Iothalamate was injected i.v. at 1600 mg I/kg body weight for 2 min. RESULTS: CM induced a transient 28% decrease in OMBF as measured with the laser Doppler. The hydrogen gas wash-out rate was reduced by 50%, indicating a reduced perfusion. CM induced a transient 60% reduction in PO2, while renal fluid and electrolyte excretion increased several fold. CONCLUSION: The CM iothalamate reduces outer medullary perfusion as estimated by two different techniques applied simultaneously. The PO2 in the same region was also reduced. Previous controversies regarding the effect of iothalamate on OMBF can be explained by extreme dosage and injection rates greatly exceeding clinical relevance.

Polyol-pathway-dependent disturbances in renal medullary metabolism in experimental insulin-deficient diabetes mellitus in rats.

AIMS/HYPOTHESIS: The renal medullary region is particularly vulnerable to reduced oxygen concentration because of its low blood perfusion and high basal oxygen consumption. This study investigated renal metabolic changes in relation to the previously observed decreased oxygen tension in streptozotocin-induced diabetic rats. METHODS: Blood perfusion, oxygen tension and consumption, interstitial pH, and glycolytic and purine-based metabolites were determined in the renal cortex and the medulla of non-diabetic and diabetic animals by, respectively, laser Doppler flowmetry, oxygen and pH microelectrodes, and microdialysis. The importance of increased polyol pathway activity for the observed alterations was investigated by daily treatment with the aldose reductase inhibitor AL-1576 throughout the course of diabetes. RESULTS: The diabetes-induced decrease in renal oxygen tension, due to augmented oxygen consumption, did not result in manifest hypoxia in either the cortical or the medullary region, as evaluated by microdialysis measurements of purine-based metabolites. The profound alterations in medullary oxygen metabolism were, however, associated with an increased lactate : pyruvate ratio and a concomitantly decreased pH. Notably, the renal medullary changes in oxygen tension, oxygen consumption, lactate : pyruvate ratio and pH were preventable by inhibition of aldose reductase. CONCLUSIONS/INTERPRETATION: Substantial metabolic changes were observed in the renal medulla in diabetic animals. These disturbances seemed to be mediated by increased polyol pathway activity and could be prevented by inhibition of aldose reductase.

Parents want to know if their child is at high risk of getting diabetes.

Not least among professionals, voices have been raised against screening research projects, which have been regarded as involving a risk of being unethical as they may disturb, scare, or even harm the included people without giving enough benefit. This problem with large-scale screening should be especially pronounced if increased risk of a serious disease like type 1 diabetes is identified when no effective prevention is available, and even more problematic if children were involved. ABIS (All Babies in Southeast Sweden) is a screening project including 17,000 newborn babies in the general population, followed prospectively to identify children at risk to get diabetes, and to study the influence of environmental factors causing the disease process. Four hundred randomly selected ABIS families received a questionnaire on attitudes and ethical questions regarding the project to be answered anonymously: 293/400 (73.3%) answered; 279/293 (95.3%) stated that they regarded it their right to be informed of results in the study and 278/293 (94.9%) said they really want to know. In fact, 254/293 (86.7%) report wanting to know if their child has increased risk of getting diabetes even if there is no preventive measure available. This clear result supports the view that this type of study may well be ethically justified as long as informed consent can be given based on adequate understanding and voluntariness. The results may have implications for the design of future screening studies.

Reactive oxygen species cause diabetes-induced decrease in renal oxygen tension.

AIMS/HYPOTHESIS: Augmented formation of reactive oxygen species (ROS) induced by hyperglycaemia has been suggested to contribute to the development of diabetic nephropathy. This study was designed to evaluate the influence of streptozotocin (STZ)-induced diabetes mellitus, as well as the effects of preventing excessive ROS formation by alpha-tocopherol treatment, on regional renal blood flow, oxygen tension and oxygen consumption in anaesthetized Wistar Furth rats. METHODS: Non-diabetic and STZ-diabetic rats were investigated after 4 weeks with or without dietary treatment with the radical scavenger DL-alpha-tocopherol (vitamin E, 5%). A laser-Doppler technique was used to measure regional renal blood flow, whilst oxygen tension and consumption were measured using Clark-type microelectrodes. RESULTS: Renal oxygen tension, but not renal blood flow, was lower throughout the renal parenchyma of diabetic rats when compared to non-diabetic control rats. The decrease in oxygen tension was most pronounced in the renal medulla. Renal cellular oxygen consumption was markedly increased in diabetic rats, predominantly in the medullary region. Diabetes increased lipid peroxidation and protein carbonylation in the renal medulla. Treatment with alpha-tocopherol throughout the course of diabetes prevented diabetes-induced disturbances in oxidative stress, oxygen tension and consumption. The diabetic animals had a renal hypertrophy and a glomerular hyperfiltration, which were unaffected by alpha-tocopherol treatment. CONCLUSIONS/INTERPRETATION: We conclude that oxidative stress occurs in kidneys of diabetic rats predominantly in the medullary region and relates to augmented oxygen consumption and impaired oxygen tension in the tissue.

Altered response in renal blood flow and oxygen tension to contrast media in diabetic rats.

PURPOSE: To investigate the effect of the contrast medium (CM) iopromide on renal microcirculation and oxygen tension in non-diabetic control and streptozotocin-diabetic Wistar Furth rats. MATERIALS AND METHODS: Oxygen tension was measured with Clark-type microelectrodes and blood flow with laser-Doppler flow probes. In order to differentiate between an acutely increased blood glucose concentration and a long-term diabetic state, some of the non-diabetic control rats were intravenously infused with glucose. RESULTS: CM decreased the medullary oxygen tension in control (non-diabetic normoglycemic) rats ( approximately 35%) but not in diabetic rats. Medullary blood flow in control rats increased after CM administration and remained elevated, while it was unchanged in the diabetic rats. In response to CM, glucose-infused control rats responded similarly to control animals in medullary oxygen tension, but similarly to diabetic rats in medullary blood flow. Contrary to in control rats, medullary oxygen tension was unchanged in diabetic animals after CM administration. CONCLUSION: Streptozotocin-diabetic rats have an altered response to intravenous injection of the CM iopromide compared to non-diabetic rats. The unaltered medullary oxygen tension, seen in the diabetic group after injection of CM, suggests that non-hemodynamic mechanisms are responsible for the increased frequency of renal failure commonly seen among diabetic patients.

Bioethical theory and practice in genetic screening for type 1 diabetes.

Due to the potential ethical and psychological implications of screening, and especially in regard of screening on children without available and acceptable therapeutic measures, there is a common view that such procedures are not advisable. As part of an independent research- and bioethical case study, our aim was therefore to explore and describe bioethical issues among a representative sample of participant families (n = 17,055 children) in the ABIS (All Babies In South-east Sweden) research screening for Type 1 diabetes (IDDM). The primary aim is the identification of risk factors important for the development of diabetes and other multifactorial immune-mediated diseases. Four hundred, randomly chosen, participant mothers were asked to complete a questionnaire exploring issues of information, informed consent, bio-material, confidentiality and autonomy, and of prevention/intervention. 293 completed the questionnaire, resulting in a response rate of 73.3%. The majority of questions had the form of 6-point Likert-type response scales (1-6). We found that the majority of respondents felt calm in in regard of samples and written material, and also concerning the possibility of their child in the future being identified as having high risk of developing Type 1 diabetes. An important finding concerning access and control of mainly biological data was indicated, with the respondents expressing concern for potential future use. We believe our findings indicate that this kind of empirical studies can substantially contribute to our understanding of bioethical issues of medical research involving genetics. Issues, such as safeguards ensuring the ethical criteria of autonomy and respect, were emphasised by our respondents. We believe the issues brought up may promote further discussion, and do suggest issues for consideration by, among others, researchers, bioethicists and Institutional Review Boards.

Et-A receptor antagonist BQ123 prevents radiocontrast media-induced renal medullary hypoxia.

PURPOSE: Renal vasoconstriction with resultant tissue hypoxia, especially in the renal medulla, has been suggested to play a role in contrast media (CM)-induced nephropathy. Endothelin (ET) is released into the blood stream following CM injection and has been proposed as a potential mediator through its vasoconstrictive properties. MATERIAL AND METHODS: To investigate the possible protective influence of ET-receptor antagonists against CM-induced reduction in renal function, we studied the effects of injection of iopromide with and without pretreatment with BQ123 (ET-A antagonist) or BQ788 (ET-B antagonist) on renal superficial cortical flow (CBF), outer medullary blood flow (OMBF) and outer medullary oxygen tension (pO2) in normal rats. RESULTS: Administration of CM (1600 mg I/kg b.w.) did not affect CBF in any of the groups. However, a transient decrease in OMBF occurred, which was unaffected by both BQ123 and BQ788. Also a transient decrease in outer medullary pO2 was induced by CM administration. The pO2 reduction was significantly smaller after pretreatment with BQ123, than after injection of CM alone or together with BQ788, and pO2 returned more rapidly to the control level. Neither receptor antagonist had an effect on CM-mediated increases in electrolyte excretion. CONCLUSION: In the normal rat, activation of ET-A receptors is partly involved in the depression of outer medullary pO2 caused by injection of iopromide. However, the decrease in OMBF after iopromide injection is not mediated by ET receptors. The beneficial effects of the ET-A receptor antagonist on CM-induced changes in outer medullary pO2 seem therefore not primarily mediated on the hemodynamic level but may rather involve tubular transport mechanisms.

Attitudes to bioethical issues: a case study of a screening project.

Commonly expressed in theoretical discussions about ethical problems in the context of epidemiology and screening is the need for more data. A study was carried out involving 21 explorative interviews with participant and nonparticipant mothers in a neonatal research screening project in progress in Sweden, ABIS (All Babies in Southeast Sweden). The respondents were asked, by way of open-ended questions, to give their opinions about certain ethical issues: informed consent; reasons for joining/declining; surrogate decision; the collection, analysis and storage of written and "live" material (biobanks); intervention etc. The ethical implications mentioned in the literature mostly concern the risk of creating distress and anxiety (anxiety and possible stigmatisation in respect of positive or false-positive results, worry about material collected and stored, distress caused by blood sampling procedures, etc.). Our results do not support the idea that the risks are substantial. The respondents rather indicate an attitude of benevolence--they are positive both to the current research on children, to the material they contribute (both written material and "biomaterial"), to possible results and intervention plans. On the other hand the participants expressed concern about the storage of material and the right to be informed of any screening/project results. Further studies in this field are needed and would be of help in theoretical discussion, the work of ethical committees and the designing of, for example, screening and research projects.

Changing dopaminergic activity through different pathways: consequences for renal sodium excretion, regional blood flow and oxygen tension in the rat.

Dopamine (DA) is an intrarenal natriuretic hormone involved in sodium homeostasis, but the regulation of renal dopaminergic tonus is unclear. We evaluated different pathways for elevating DA tonus to determine which are important for the ability of the kidney to produce natriuresis and studied the accompanying effects on regional renal blood flow and oxygen tension. Thus, we compared the effects of a catechol-O-methyl transferase (COMT)-inhibitor, an unspecific monoamine oxidase (MAO)-inhibitor, a D1-like receptor agonist and a DA precursor in anaesthetized rats. Sodium excretion increased sixfold after COMT inhibition, eightfold after administration of the D1-like agonist, whereas it was similar to control after MAO inhibition and infusion of DA precursor. Urinary dopamine excretion increased 42% by COMT inhibition, 55% by MAO inhibition and 12-fold after DA precursor, but remained unchanged after infusion of the D1-like agonist. The D1-like receptor agonist led to a 38% increase in the cortical blood flow and a 21% increase in outer medullary blood flow. Regional renal blood flow was unaffected by all other treatments. Cortical and outer medullary oxygen tension was unaffected in all treatment groups. To conclude, the natriuretic and haemodynamic properties of an elevation in DA tonus depends on the route by which the elevation occurred. Systemic administration of a D1-like receptor agonist, results in a natriuretic response which, as opposed to the natriuresis seen after COMT inhibition, coincides with an increase in renal cortical and outer medullary blood flow. Precursor delivery or MAO inhibition did not change neither urinary sodium excretion nor renal blood flow.

Markedly decreased oxygen tension in transplanted rat pancreatic islets irrespective of the implantation site.

In this study, we syngeneically transplanted islets to three different implantation sites of diabetic and nondiabetic rats, then 9-12 weeks later we measured the blood perfusion and compared the tissue partial pressure of oxygen (PO2) levels of these transplanted islets to endogenous islets. Modified Clark microelectrodes (outer tip diameter 2-6 microm) were used for the oxygen tension measurements, and islet transplant blood perfusion was recorded by laser-Doppler flowmetry (probe diameter 0.45 mm). The islet graft blood perfusion was similar in all islet grafts, irrespective of the implantation site. In comparison, the three implantation organs (the kidney cortex, liver, and spleen) differed markedly in their blood perfusion. There were no differences in islet graft blood perfusion between diabetic and nondiabetic recipients. Within native pancreatic islets, the mean PO2 was approximately 40 mmHg; however, all transplanted islets had a mean PO2 of approximately 5 mmHg. The oxygen tension of the grafts did not differ among the implantation sites. In diabetic recipients, an even lower PO2 level was recorded in the islet transplants. We conclude that the choice of implantation site seems less important than intrinsic properties of the transplanted islets with regard to the degree of revascularization and concomitant blood perfusion. Furthermore, the mean PO2 level in islets implanted to the kidney, liver, and spleen was markedly decreased at all three implantation sites when compared with native islets, especially in diabetic recipients. These results are suggestive of an insufficient oxygenization of revascularized transplanted islets, irrespective of the implantation site.

Transient glomerular hyperfiltration in the streptozotocin-diabetic Wistar Furth rat.

The glomerular hemodynamic response to streptozotocin (STZ)-induced experimental diabetes differs depending on metabolic control and rat strain used. The present study characterize the glomerular filtration rate (GFR) and other renal parameters, weekly up to eight weeks of diabetes in STZ-diabetic Wistar Furth rats. The STZ-treated rats became diabetic within 24 h after treatment and retained a blood glucose concentration of 20-25 mmol/l throughout the experimental period. The GFR was transiently increased during the first 3-5 weeks after induction of diabetes, but thereafter did not differ from control animals. The renal weight increased by approximately 50% during the first week after induction of diabetes, thereafter no further increase in weight occurred. The urinary flow rate and urinary osmolar excretion were approximately 10 times higher in diabetic animals when compared to non-diabetic animals. Although they remained markedly higher than in non-diabetic animals, both the urinary flow rate and the urinary osmolar excretion peaked after 3 weeks of diabetes and thereafter tended to decrease. The urinary sodium and potassium excretions did not differ between non-diabetic and diabetic animals. We conclude that the transient increase in the GFR seen in the human disease, occurs in Wistar Furth rats, which is in contrast to a majority of other rat strains, where the GFR is persistently increased.

Engraftment and growth of transplanted pancreatic islets.

Transplantation of pancreatic islets may provide a cure for type 1 diabetes. However, this treatment can currently be offered only to very few patients. To improve transplantation success we need to understand better the mechanisms of how the implanted islets survive, grow and/or maintain adequate function. We herein report on our studies to evaluate the factors responsible for the engraftment, i.e. revascularization, reinnervation etc., of transplanted islets and relate these factors to the metabolism and growth of the islets. Graft metabolism can be monitored by microdialysis probes that allow for the measurement of minute amounts of islet metabolites and hormonal products. Growth of the endocrine cells can be stimulated both in vitro before implantation and in vivo post-transplantation. Another problem is rejection of transplanted islets, which may be overcome by the microencapsulation of islets. The knowledge gained by the present studies will enable us to elucidate the optimal treatment of islets to ensure a maximal survival of the transplanted islets, and may be applied also to clinical islet transplantation.

Oscillations in oxygen tension and insulin release of individual pancreatic ob/ob mouse islets.

AIMS/HYPOTHESIS: The role of beta-cell metabolism for generation of oscillatory insulin release was investigated by simultaneous measurements of oxygen tension (pO2) and insulin release from individual islets of Langerhans. METHODS: Individual islets isolated from the ob/ob-mice were perifused. Insulin in the perifusate was measured with a sensitive ELISA and PO2 with a modified Clark-type electrode inserted into the islets. RESULTS: In the presence of 3 mmol/l D-glucose, PO2 was 102 +/- 9 mmHg and oscillatory (0.26 +/- 0.04 oscillations/min). Corresponding insulin measurements showed oscillatory release with similar periodicity (0.25 +/- 0.02 oscillations/min). When the D-glucose concentration was increased to 11 mmol/l, PO2 decreased by 30% to 72 +/- 10 mmHg with maintained frequency of the oscillations. Corresponding insulin secretory rate rose from 5 +/- 2 to 131 +/- 16 pmol x g(-1) x s(-1) leaving the frequency of the insulin pulses unaffected. The magnitude of glucose-induced change in pO2 varied between islets but was positively correlated to the amount of insulin released (r2 = 0.85). When 1 mmol/l tolbutamide was added to the perifusion medium containing 11 mmol/l glucose no change in average oscillatory pO2 was observed despite a doubling in the secretory rate. When 8 mmol/l 3-oxymethyl glucose was added to perifusion medium containing 3 mmol/l D-glucose, neither pO2 nor insulin release of the islets were changed. Temporal analysis of oscillations in pO2 and insulin release revealed that maximum respiration correlated to maximum or close to maximum insulin release. CONCLUSION/INTERPRETATION: The temporal relation between oscillations in pO2 and insulin release supports a role for metabolic oscillations in the generation of pulsatile insulin release.

Photoreduction and evolution of mercury from seawater

The photoreduction of mercury (Hg2+ to Hg0) in natural seawater was investigated by means of a radiotracer (203Hg2+) solution exposed to natural and simulated sunlight. Different light regimes (dark, natural daylight, and a solar simulator), and dissolved organic carbon (DOC) levels from commercially available humic acids concentrations, were tested in the laboratory to evaluate the possibility of occurrence of the reaction in the environment. The natural seawater prepared accordingly to each experimental condition was continuously purged of the Hg0 formed, which was then re-oxidised in an acid trap and determined. The use of a solar simulator permitted the test of light intensity and wavelength dependence of the process under investigation. The reaction is dependent on the concentration of DOC in the experimental solution, increasing light intensity and decreasing wavelength. Reduction rates were in the range of 0.04-2.2% h(-1) for the DOC concentrations and light regimes tested. The process might have geochemical implications for the cycling of mercury around the air-sea interface.

Use of a modified oxygen microelectrode and laser-Doppler flowmetry to monitor changes in oxygen tension and microcirculation in a flap.

Flap failure is a clinical problem in free tissue transfer, and there is no reliable device for monitoring the tissue. Differentiating between an arterial occlusion and venous congestion is also a problem. A study was undertaken to monitor viability in a pedicled groin flap and to compare two different monitoring methods. The oxygen tension in the flap, measured with a modified Clark-type microelectrode (tip diameter = 3 to 8 microm; 90 percent response within 2.6 +/- 0.5 seconds), was compared with changes in blood flow in the flap, measured with a laser-Doppler probe. In 11 Sprague-Dawley rats, the changes in oxygen tension and blood flow in the pedicled groin flap were studied after clamping and subsequent reperfusion of the artery or vein. After occlusion of the artery to the flap, oxygen tension decreased to a stable value (i.e., the recording level remained unchanged for 30 seconds), from 19.7 +/- 1.8 to 0.3 +/- 0.1 mmHg, after 193 +/-25 seconds; blood flow decreased to a stable value, from 117 +/- 21 to 54 +/- 18 perfusion units, after 26 +/- 6 seconds. Clamping of the vein resulted in a decrease in oxygen tension, from 17.1 +/- 1.8 to 1.4 +/- 0.7 mmHg, after 416 +/- 67 seconds, and blood flow decreased to a stable value, from 90 +/- 14 to 35 +/- 6 perfusion units, after 107 +/- 27 seconds. The results of this study show that there is a difference in oxygen tension and blood flow responses between arterial and venous occlusion and that it may be possible with both methods to distinguish arterial from venous occlusion. However, although oxygen tension measurements are slightly slower in response than laser-Doppler measurements, the values are more reliable as a diagnostic tool for interpretation of a vessel occlusion.