| 1. |
- Guan, Na N., et al.
(author)
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Release and inhibitory effects of prostaglandin D2 in guinea pig urinary bladder and the role of urothelium
- 2014
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In: Biochimica et Biophysica Acta. - Amsterdam, Neterhlands : Elsevier. - 0006-3002 .- 1878-2434 .- 0304-4165. ; 1840:12, s. 3443-3451
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Journal article (peer-reviewed)abstract
- BACKGROUND: While studying a urothelium-derived inhibitory factor in guinea pig urinary bladders we observed considerable release of prostanoids, including PGD2-like activity. The present study was carried out to identify the prostanoids and to study their roles in modulating guinea pig urinary bladder motility.METHODS: Release of PGE2 and PGD2 in isolated guinea pig urinary bladder preparations was analyzed by high performance liquid chromatography (HPLC) combined with bioassay on bladder strips. Isolated urothelium-intact (UI) or -denuded (UD) bladder strips were subjected to electrical field stimulation (EFS) and applications of PGE2 and PGD2.RESULTS: A resting release of 95±9 (n=5) nggtissue(-1)h(-1) PGE2-like activity and 210±34 (n=4) nggtissue(-1)h(-1) PGD2-like activity was found, where PGD2-like was subject to marked spontaneous inactivation during isolation. Prostanoids release was decreased by 70-90% by the cyclo-oxygenase inhibitor diclofenac in UI preparations. Urothelium removal decreased prostanoids release by more than 90%. PGE2 increased basal tone and spontaneous contractions, whereas PGD2 had little or no effect on these. Exogenous PGE2 enhanced and PGD2 inhibited contractile responses to EFS, exogenous acetylcholine- and ATP, whereas PGD2 caused marked dose-dependent inhibition. PGE2 and PGD2 effects were more pronounced in diclofenac-treated UD tissues.CONCLUSIONS: PGD2 and PGE2 are released from guinea pig bladder urothelium and PGD2 has inhibitory effects on bladder motility, mainly through a postjunctional action on smooth muscle responsiveness.GENERAL SIGNIFICANCE: The release and inhibitory effects merit further studies in relation to normal biological function as well as overactive bladder syndrome.
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| 2. |
- Hörer, Tal M., 1971-, et al.
(author)
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Intraperitoneal Metabolic Consequences of Supraceliac Aortic Balloon Occlusion in an Experimental Animal Study Using Microdialysis
- 2014
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In: Annals of Vascular Surgery. - : Elsevier. - 0890-5096 .- 1615-5947. ; 28:5, s. 1286-1295
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Journal article (peer-reviewed)abstract
- Background: To investigate the effects of supraceliac aortic balloon occlusion (ABO) and superior mesenteric artery (SMA) occlusion on abdominal visceral metabolism in an animal model using intraperitoneal microdialysis (IPM) and laser Doppler flowmetry.Methods: A total of 9 pigs were subjected to ABO and 7 animals were subjected to SMA occlusion for 1 hour followed by 3 hours of reperfusion. Seven animals served as controls. Hemodynamic data, arterial blood samples, urinary output, and intestinal mucosal blood flow (IBF) were followed hourly. Intraperitoneal (i.p) glucose, glycerol, lactate, and pyruvate concentrations and lactate-to-pyruvate (lip) ratio were measured using IPM.Results: Compared with the baseline, ABO reduced IBF by 76% and decreased urinary output. SMA occlusion reduced IBF by 75% without affecting urinary output. ABO increased the i.p lip ratio from 18 at baseline, peaking at 46 in early reperfusion. SMA occlusion and reperfusion tended to increase the i.p lip ratio, peaking at 36 in early reperfusion. ABO increased the i.p glycerol concentration from 87 mu M at baseline to 579 p,M after 3 hours of reperfusion. SMA occlusion and reperfusion increased The i.p glycerol concentration but to a lesser degree.Conclusions: Supraceliac ABO caused severe hemodynamic, renal, and systemic metabolic disturbances compared with SMA occlusion, most likely because of the more extensive ischemia-reperfusion injury. The intra-abdominal metabolism, measured by microdialysis, was affected by both ABO and SMA occlusion but the most severe disturbances were caused by ABO. The i.p lip ratios and the glycerol concentrations increased during ischemia and reperfusion and may serve as markers of these events and indicate anaerobic metabolism and cell damages respectively.
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| 3. |
- Nilsson, Kristofer F., 1981-, et al.
(author)
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Estimation of endogenous adenosine activity at adenosine receptors in guinea-pig ileum using a new pharmacological method
- 2010
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In: Acta Physiologica. - : Blackwell Publishing. - 1748-1708 .- 1748-1716. ; 199:2, s. 231-241
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Journal article (peer-reviewed)abstract
- AIM: Adenosine modulates neurotransmission and in the intestine adenosine is continuously released both from nerves and from smooth muscle. The main effect is modulation of contractile activity by inhibition of neurotransmitter release and by direct smooth muscle relaxation. Estimation of adenosine concentration at the receptors is difficult due to metabolic inactivation. We hypothesized that endogenous adenosine concentrations can be calculated by using adenosine receptor antagonist and agonist and dose ratio (DR) equations.METHODS: Plexus-containing guinea-pig ileum longitudinal smooth muscle preparations were made to contract intermittently by electrical field stimulation in organ baths. Schild plot regressions were constructed with 2-chloroadenosine (agonist) and 8-(p-sulfophenyl)theophylline (8-PST; antagonist). In separate experiments the reversing or enhancing effect of 8-PST and the inhibiting effect of 2-chloroadenosine (CADO) were analysed in the absence or presence of an adenosine uptake inhibitor (dilazep), and nucleoside overflow was measured by HPLC.RESULTS: Using the obtained DR, baseline adenosine concentration was calculated to 28 nm expressed as CADO activity, which increased dose dependently after addition of 10(-6) m dilazep to 150 nm (P < 0.05). HPLC measurements yielded a lower fractional increment (80%) in adenosine during dilazep, than found in the pharmacological determination (440%).CONCLUSION: Endogenous adenosine is an important modulator of intestinal neuro-effector activity, operating in the linear part of the dose-response curve. Other adenosine-like agonists might contribute to neuromodulation and the derived formulas can be used to calculate endogenous agonist activity, which is markedly affected by nucleoside uptake inhibition. The method described should be suitable for other endogenous signalling molecules in many biological systems.
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| 4. |
- Nilsson, Kristofer F., 1981-, et al.
(author)
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Formation of new bioactive organic nitrites and their identification with gas chromatography-mass spectrometry and liquid chromatography coupled to nitrite reduction
- 2011
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In: Biochemical Pharmacology. - : Elsevier. - 0006-2952 .- 1356-1839 .- 1873-2968. ; 82:3, s. 248-259
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Journal article (peer-reviewed)abstract
- Nitric oxide (NO) donors, notably organic nitrates and nitrites are used therapeutically but tolerance develops rapidly, making the use of e.g. nitroglycerin difficult. NO donation in the pulmonary vascular bed might be useful in critically ill patients. Organic nitrites are not associated with tachyphylaxis but may induce methaemoglobinemia and systemic hypotension which might hamper their use. We hypothesised that new lung-selective NO donors can be identified by utilizing exhaled NO as measure for pulmonary NO donation and systemic arterial pressure to monitor hypotension and tolerance development. Solutions of alcohols and carbohydrates were reacted with NO gas and administered to ventilated rabbits for evaluation of in vivo NO donation. Chemical characterization was made by liquid chromatography with on-line nitrite reduction (LC-NO) and by gas chromatography-mass spectrometry (GC-MS). In vivo experiments showed that the hydroxyl-containing compounds treated with NO gas yielded potent NO donors, via nitrosylation to organic nitrites. Analyses by LC-NO showed that the reaction products were able to release NO in vitro. In GC-MS the reaction products were determined to be the organic nitrites, where some are new chemical entities. Non-polar donors preferentially increased exhaled NO with less effect on systemic blood pressure whereas more polar molecules had larger effects on systemic blood pressure and less on exhaled NO. We conclude that new organic nitrites suitable for intravenous administration are produced by reacting NO gas and certain hydroxyl-containing compounds in aqueous solutions. Selectivity of different organic nitrites towards the pulmonary and systemic circulation, respectively, may be determined by molecular polarity.
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| 5. |
- Nilsson, Kristofer F
(author)
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Nitric oxide in experimental pulmonary embolism
- 2010
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Doctoral thesis (other academic/artistic)abstract
- Nitric oxide (NO) is an important modulator of the pulmonary circulation both at basal state and in pulmonary hypertension. Low levels of NO are detectable in exhaled gas which is believed to mirror pulmonary NO formation and elimination. Pulmonary embolism is a disease characterised by pulmonary hypertension, and thereby increased afterload of the right ventricle, and by disturbed gas exchange which produces hypoxemia. The role of NO in acute pulmonary embolism was studied in two animal models. The fraction of NO in exhaled gas increased dramatically after induction of acute pulmonary embolisation with both gas and solid emboli. It was found that approximately 50% of the increased exhaled NO could be reversed by normalising the airway/alveolar carbon dioxide concentration, thus indicating a regulatory role of carbon dioxide on pulmonary NO production in this condition. Endogenous NO production exerts a protective effect in acute pulmonary embolism since it was found that inhibition of endogenous NO production in combination with pulmonary embolisation resulted in a severely augmented hemodynamic response and significantly impaired the survival in this condition. Therefore it was further hypothesised that exogenous NO might be protective in this condition. NO donor compounds, some of which were novel organic nitrites, with increased selectivity towards the pulmonary circulation were developed. Intravenously administered organic nitrites reduced the pulmonary hypertension and relieved the strain on the right ventricle in acute pulmonary embolism without adverse effects in the form of systemic hypotension, methaemoglobin formation and tolerance development. Methods for identification and characterisation of organic nitrites were described, including a novel HPLC-NO/nitrite analysis. These studies show that exhaled NO is increased after acute pulmonary embolism thus emerging as a potential diagnostic aid in this condition. Endogenous NO is protective in acute pulmonary embolism which provides further knowledge on the role of NO in the pulmonary circulation. Exogenous NO, in the form of certain organic nitrites, exerts beneficial effects in acute pulmonary embolism, thus rendering organic nitrites as a potential future life-saving treatment in acute pulmonary embolism. Future studies will investigate the effects of organic nitrites in experimental models of other life-threatening diseases with compromised pulmonary circulation.
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| 6. |
- Skoog, Per, 1975-, et al.
(author)
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Abdominal Hypertension and Decompression : The Effect on Peritoneal Metabolism in an Experimental Porcine Study
- 2014
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Other publication (other academic/artistic)abstract
- Objective: This study aims to investigate the abdominal metabolic response and circulatory changes after decompression of intra-abdominal hypertension in a porcine model. Design: Prospective study with controls. Setting: University hospital research laboratory.Subjects: Three-months old domestic pigs of both sexes. Interventions: The animals were anesthetised and ventilated. Nine animals had a pneumoperitoneum-induced intra-abdominal hypertension of 30 mmHg for six hours. Twelve animals had corresponding intra-abdominal hypertension for four hours followed by decompression and were monitored for another two hours.Measurements and Main Results: Hemodynamics, urine output and arterial blood samples were analysed. Laserdoppler measured mucosal blood flow and urine output decreased with pressure induction and showed a statistically significant restitution after decompression. Glucose, glycerol, lactate and pyruvate concentrations and lactate-pyruvate (l/p) ratio were measured by microdialysis. Both groups developed distinct metabolic changes intraperitoneally at pressure induction including an increased l/p ratio as signs of organ hypoperfusion. In the decompression group the intraperitoneal l/p ratio normalised during the second decompression hour, indicating partially restored perfusion.Conclusions: Decompression after four hours of intra-abdominal hypertension results in restoration of intestinal blood flow and normalised intraperitoneal metabolism.
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| 7. |
- Skoog, P., et al.
(author)
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Abdominal Hypertension and Decompression : The Effect on Peritoneal Metabolism in an Experimental Porcine Study
- 2014
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In: European Journal of Vascular and Endovascular Surgery. - : W.B. Saunders Ltd. - 1078-5884 .- 1532-2165. ; 47:4, s. 402-410
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Journal article (peer-reviewed)abstract
- Objective: The aim of this study was to investigate the abdominal metabolic response and circulatory changes after decompression of intra-abdominal hypertension in a porcine model.Methods: This was an experimental study with controls. Three-month-old domestic pigs of both sexes were anesthetized and ventilated. Nine animals had a pneumoperitoneum-induced IAH of 30 mmHg for 6 hours. Twelve animals had the same IAN for 4 hours followed by decompression, and were monitored for another 2 hours. Hemodynamics, including laser Doppler-measured mucosal blood flow, urine output, and arterial blood samples were analyzed every hour along with glucose, glycerol, lactate and pyruvate concentrations, and lactate-pyruvate (l/p) ratio, measured by microdialysis.Results: Laser Doppler-measured mucosal blood flow and urine output decreased with the induction of IAH and showed a statistically significant resolution after decompression. Both groups developed distinct metabolic changes intraperitoneally on induction of IAH, including an increased l/p ratio, as signs of organ hypoperfusion. In the decompression group the intraperitoneal l/p ratio normalized during the second decompression hour, indicating partially restored perfusion.Conclusion: Decompression after 4 hours of IAH results in an improved intestinal blood flow and a normalized intraperitoneal lip ratio.
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