Vitamin D receptor activation with paricalcitol can modulate the transcription of renin-angiotens... more Vitamin D receptor activation with paricalcitol can modulate the transcription of renin-angiotensin system components in the surgical 5/6 nephrectomy rat model (5/6 NX) of chronic renal insufficiency. We tested the hypothesis whether dietary modification of phosphate influences kidney renin-angiotensin system gene expression at the mRNA level in 5/6 NX rats. Fifteen weeks after surgery, rats were given control diet (0.3% calcium, 0.5% phosphate), phosphate-lowering diet (3% calcium as carbonate) or high-phosphate diet (1.5%) for 12 weeks. Sham-operated rats were on control diet. Blood pressure, plasma phosphate, parathyroid hormone, glomerulosclerosis, tubulointerstitial damage, and FGF-23 were increased in remnant kidney rats, whereas creatinine clearance was decreased. Phosphate, parathyroid hormone, glomerulosclerosis, tubulointerstitial damage, and FGF-23 were further elevated by the high-phosphate diet, but were reduced by the phosphate-lowering diet. Plasma calcium was increased with the phosphate-lowering diet and decreased with the high-phosphate diet. Remnant kidney rats on control diet showed upregulated kidney angiotensin-converting enzyme (ACE) and angiotensin (Ang) IV receptor (AT(4)) transcription, while ACE2, Ang II type 2 receptor and renin receptor transcription were downregulated in comparison with sham rats. Phosphate-lowering diet reduced whereas high-phosphate diet increased kidney ACE, and these effects were observed at both mRNA and protein levels. Dietary phosphate loading also resulted in lower AT(1a) gene transcription. Dietary phosphate loading was associated with elevated kidney ACE expression, increased tissue damage and lower AT(1a) transcription in 5/6 NX rats. Phosphate binding with 3% calcium carbonate had opposite effects on ACE and kidney damage.
Catecholamines and other catecholic compounds have opposite effects on the cyclooxygenase and 5-l... more Catecholamines and other catecholic compounds have opposite effects on the cyclooxygenase and 5-lipoxygenase pathways of arachidonic acid metabolism in human polymorphonuclear leukocytes and whole blood in vitro. The hypothesis that high levels of adrenaline, found e.g. in myocardial infarction, are involved in the regulation of arachidonic acid metabolism was tested. Adrenaline (0.1 micrograms/kg per min for 45 min and thereafter 0.2 micrograms/kg per min for 15 min) was infused to healthy male volunteers to mimic relationships between high levels of adrenaline and arachidonic acid metabolism in myocardial infarction. Adrenaline infusion increased Ca ionophore A23187-induced TXB2 formation in whole blood. The effect was smaller when spontaneous clotting was used as a stimulus. Urinary 11-dehydro-TXB2 excretion, an indicator of total in vivo thromboxane synthesis, increased twofold. Adrenaline infusion decreased both LTB4 and LTE4 synthesis in A23187-stimulated whole blood. These results demonstrate that high levels of adrenaline influence the cyclooxygenase and 5-lipoxygenase pathways of arachidonic acid metabolism differentially in man.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society
Functional and morphological changes of blood vessels in cyclosporine A (CsA)-induced hypertensio... more Functional and morphological changes of blood vessels in cyclosporine A (CsA)-induced hypertension and nephrotoxicity were studied in spontaneously hypertensive rats (SHR). The role of the L-arginine-nitric oxide (NO) pathway and the importance of oxidative stress in CsA toxicity were also assessed. SHR (7-8 week old) on a high-sodium diet were treated with CsA (5 mg kg(-1) d(-1) s.c.) for 6 weeks. A proportion of the rats were treated concomitantly with the NO precursor L-arginine (1.7 g kg(-1)d(-1) p.o.). CsA elevated blood pressure and caused renal dysfunction and morphological nephrotoxicity. CsA also impaired mesenteric and renal arterial function and caused structural damage to intrarenal and extrarenal small arteries and arterioles. Medial atrophy of the mesenteric resistance vessels and decreased viability of smooth muscle cells of the thoracic aorta were observed. Renal and arterial damage was associated with the presence of inflammatory cells. CsA did not affect markers of...
Journal of Chromatography B: Biomedical Sciences and Applications, 1984
Thin-layer chromatography (TLC) is widely used for the separation and identification of a number ... more Thin-layer chromatography (TLC) is widely used for the separation and identification of a number of arachidonic acid metabolites. There are descriptions of many TLC methods by which a variety of prostanoids can be separated [l--8].
Obstructive sleep apnoea (OSA) carries an increased risk of ischaemic stroke, but the underlying ... more Obstructive sleep apnoea (OSA) carries an increased risk of ischaemic stroke, but the underlying mechanism is not clear. As right-to-left shunting can occur through a patent foramen ovale (PFO) during periods of apnoea, we investigated nocturnal changes in fibrinolytic activity and platelet function in subjects who had OSA with or without PFO and in controls. We determined plasminogen activator inhibitor 1 (PAI-1) activity and antigen and platelet activation parameters. The severity of OSA was verified by polygraphy and PFO was detected by ear oximetry. We found a higher PAI-1 activity and antigen and a lower ratio of 2,3-dinor-PGF(1α) to 2,3-dinor-TXB(2) in the subjects with OSA than in the controls. Linear regression analysis showed the apnoea-hypopnoea index (β-coefficient, 0.499; P = 0.032) and PFO (β-coefficient, 0.594; P = 0.015) to be associated independently with PAI-1 activity in the morning, while the increment in PAI-1:Ag from evening to morning was significantly associat...
Prostaglandins, leukotrienes, and essential fatty acids, 2003
Our purpose was to determine urinary 9 alpha,11 beta-prostaglandin F2, the primary metabolite of ... more Our purpose was to determine urinary 9 alpha,11 beta-prostaglandin F2, the primary metabolite of prostaglandin D2, in pregnancies at high risk for hypertensive disorders and the effect of acetylsalicylic acid on 9 alpha,11 beta-prostaglandin F2. Ninety high risk women were randomised to acetylsalicylic acid and placebo groups at 12-14 weeks of gestation, with 43 women in both groups followed up successfully. 9 alpha,11 beta-prostaglandin F2 was determined at baseline, at 24-26, and at 32-34 weeks of gestation. Fifteen normotensive non-pregnant women, 17 normotensive pregnant women at 12-14, and 15 at 30-34 weeks of gestation served as controls. Urinary 9 alpha,11 beta-prostaglandin F2 was significantly higher in pregnant women at 12-14 weeks of gestation as compared to non-pregnant women. High risk pregnancies had higher 9 alpha,11 beta-prostaglandin F2 as compared to normotensive pregnancies at 12-14, and at 30-34 weeks of gestation. Urinary 9 alpha,11 beta-prostaglandin F2 increas...
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2000
Smoking is an important risk factor for respiratory and cardiovascular diseases. The role of nume... more Smoking is an important risk factor for respiratory and cardiovascular diseases. The role of numerous chemical, partly uncharacterised compounds existing in tobacco smoke is not known. (-)-Nicotine, its stereoisomer (+)-nicotine and main metabolite cotinine are biologically active compounds influencing e.g. catecholamine and eicosanoid systems. The precise mechanisms are not well known. The purpose of the present study consisting of a PhD thesis (11) and five original papers was to investigate the in vitro effects of nicotine isomers and cotinine on eicosanoid production in polymorphonuclear leukocytes, platelets and whole blood in vitro, and to clarify the effects of smoking without and with nicotine substitution on eicosanoid production in vivo and ex vivo. It was found that all the tested compounds modulated blood cell eicosanoid synthesis. Nicotine isomers and cotinine increased PGE2 but decreased TXB2, LTB4 and LTE4 synthesis in vitro. Eicosanoid synthesis in vivo and ex vivo w...
To compare the effects of unreamed and reamed intramedullary nailing on the systemic production o... more To compare the effects of unreamed and reamed intramedullary nailing on the systemic production of prostacyclin and thromboxane A2 as assessed, respectively, by determinations of urinary 2,3-dinor-6-ketoprostaglandin F1alpha and 11-dehydrothromboxane B2 excretion. Ten otherwise healthy patients with closed and simple tibial shaft fractures were treated with unreamed intramedullary nailing, and 10 otherwise healthy patients with closed and simple tibial shaft fractures were treated with reamed intramedullary nailing. Urine was collected preoperatively and during the next 5 postoperative days. The samples were stored at -70 degrees C until assayed at the end of the study. In the unreamed group, urinary 2,3-dinor-6-ketoprostaglandin F1alpha and 11-dehydrothromboxane B2 excretion remained stable and at a significantly lower levels compared with the reamed group during the entire study period (p < 0.021). In the reamed group, the alteration in urinary 2,3-dinor-6-ketoprostaglandin F1a...
We investigated the effects of nicotine and cotinine (0.5 nM-0.5 mM) on prostaglandin E2 and leuk... more We investigated the effects of nicotine and cotinine (0.5 nM-0.5 mM) on prostaglandin E2 and leukotriene B4 production in human polymorphonuclear leukocytes and on thromboxane B2 formation in human platelet-rich plasma, stimulated by calcium ionophore A23187. Nicotine and cotinine dose-dependently increased prostaglandin E2 synthesis in polymorphonuclear leukocytes from 25% (0.5 nM) up to nearly four-fold (0.5 mM). In concentrations found in the plasma of smokers, nicotine and cotinine increased prostaglandin E2 production by 33% (50 nM) and 50% (500 nM), respectively. Nicotine and cotinine equipotentially reduced both leukotriene B4 production in polymorphonuclear leukocytes and thromboxane B2 production in platelet rich plasma, the inhibition increasing from 20% (0.5 nM) to 60% (0.5 mM). The stimulation of prostaglandin E2 and inhibition of leukotriene B4 and thromboxane B2 production by nicotine and cotinine may due to the pyridine moiety that these compounds have in common.
Catecholamines (adrenaline, dopamine, isoprenaline, noradrenaline) and caffeic acid (catecholic c... more Catecholamines (adrenaline, dopamine, isoprenaline, noradrenaline) and caffeic acid (catecholic compound without adrenergic receptor activity) decreased leukotriene (LT)B4 synthesis in A23187-stimulated human whole blood. Salbutamol, a non-catecholic beta 2-adrenergic agonist, did not influence LTB4 synthesis. Catecholamines stimulated thromboxane (TX)B2 synthesis with a concomitant inhibition of LTB4 synthesis; caffeic acid and salbutamol did not stimulate TXB2 synthesis. These results, obtained in A23187-stimulated whole blood, which also takes into account the complex interaction between different cell types, are similar to our previous results with polymorphonuclear leukocytes. Catecholamines show an opposite effect on lipoxygenase and cyclooxygenase pathways, which may give rise to a marked change in LT/TX ratio in physiological or pathological conditions where sufficient concentrations of catecholamines are present.
Our aim was to compare the effects of calcium carbonate and sevelamer-HCl treatments on calcium-p... more Our aim was to compare the effects of calcium carbonate and sevelamer-HCl treatments on calcium-phosphate metabolism and renal function in 5/6 nephrectomized (NX) rats so that long-term disease progression preceded the treatment. After 15-week progression, calcium carbonate (3.0%), sevelamer-HCl (3.0%), or control diets (0.3% calcium) were given for 9 weeks. Subtotal nephrectomy reduced creatinine clearance (−40%), plasma calcidiol (−25%), and calcitriol (−70%) and increased phosphate (+37%), parathyroid hormone (PTH) (11-fold), and fibroblast growth factor-23 (FGF-23) (4-fold). In NX rats, calcium carbonate diet increased plasma (+20%) and urinary calcium (6-fold), reduced plasma phosphate (−50%) and calcidiol (−30%), decreased creatinine clearance (−35%) and FGF 23 (−85%), and suppressed PTH without influencing blood pH. In NX rats, sevelamer-HCl increased urinary calcium (4-fold) and decreased creatinine clearance (−45%), PTH (−75%), blood pH (by 0.20 units), plasma calcidiol (−40%), and calcitriol (−65%). Plasma phosphate and FGF-23 were unchanged. In conclusion, when initiated after long-term progression of experimental renal insufficiency, calcium carbonate diet reduced plasma phosphate and FGF-23 while sevelamer-HCl did not. The former induced hypercalcemia, the latter induced acidosis, while both treatments reduced vitamin D metabolites and deteriorated renal function. Thus, delayed initiation influences the effects of these phosphate binders in remnant kidney rats.
Nitric Oxide and Free Radicals in Peripheral Neurotransmission, 2000
... The reperfusion period following transient coronary occlusion is associated with accumulation... more ... The reperfusion period following transient coronary occlusion is associated with accumulation of neutrophils, which probably contribute to myocardial damage (Brady et aI., 1992; Tsao and Lefer, 1990). ... Br.l Urol. 78:257-261. Brady, AJ, Williams, EM., and Williams, TJ 1992. ...
Prostaglandins, Leukotrienes and Essential Fatty Acids, 2001
It has previously been shown that leukotriene E4 production is increased both in acute and chroni... more It has previously been shown that leukotriene E4 production is increased both in acute and chronic lower limb ischaemia.The aim of this study was to measure the effect of revascularisation on leuktriene E4 excretion in chronic lower limb ischaemia. Revascularisation did not affect significantly on leukotriene E4 excretion (preop. 34.9þ7. 1pg/mg creatinine, postop. 24.5þ4.7 pg/mg creatinine, n=10, P50.238 ).We suggest that the enhanced leukotriene E4 production continues after revascularisation which may have a therapeutical implication.
Prostaglandins, Leukotrienes and Essential Fatty Acids, 2003
Our purpose was to determine urinary 9a;11b-prostaglandin F 2 , the primary metabolite of prostag... more Our purpose was to determine urinary 9a;11b-prostaglandin F 2 , the primary metabolite of prostaglandin D 2 , in pregnancies at high risk for hypertensive disorders and the effect of acetylsalicylic acid on 9a;11b-prostaglandin F 2 .
We have previously demonstrated that adrenaline infusion increases the thromboxane/leukotriene (T... more We have previously demonstrated that adrenaline infusion increases the thromboxane/leukotriene (TX/LT) ratio in whole blood in healthy volunteers. The aim of the present study was to see whether other catecholamines -noradrenaline and dopamine -are also capable of modulating arachidonic acid (AA) metabolism in man. Low doses of noradrenaline (0.025 gg/kg/min) and dopamine (3.0 g/kg/min), which did not change hemodynamics, were infused for 60m in into healthy male volunteers. Both dopamine and noradrenaline decreased TX synthesis stimulated by spontaneous clotting, but no remarkable effect was seen when calcium ionophore A23187 was used as a stimulus. Dopamine but not noradrenaline increased prostaglandin E 2 (PGE2) synthesis in A23187-stimulated whole blood. They both marginally decreased LTB4 formation in A23187-stimulated whole blood. The findings indicate that not only adrenaline but also noradrenaline and dopamine modulate AA metabolism in man.
Naunyn-Schmiedeberg's Archives of Pharmacology, 2001
This study investigated the effects of smoking cessation with and without nicotine substitution o... more This study investigated the effects of smoking cessation with and without nicotine substitution on the excretion of major urinary metabolites of thromboxane A 2 and prostacyclin, 11-dehydrothromboxane B 2 and 2,3-dinor-6-ketoprostaglandin F 1α , respectively, as well as on the excretion of leukotriene E 4 in man. Urine samples were obtained from 20 healthy non-smoking controls and from 60 healthy smoking volunteers before, and 3, 7 and 14 days after smoking cessation. Fifteen smokers quit smoking without nicotine substitution, 15 used nicotine chewing gum and 30 used nicotine patches as a substitution therapy. Urinary thiocyanate as well as cotinine and trans-3'-hydroxycotinine excretions were used as compliance and nicotine substitution indicators.
In this study we investigated the relationship between melatonin pathway and multiple sclerosis (... more In this study we investigated the relationship between melatonin pathway and multiple sclerosis (MS) in a high-risk Finnish population by studying the single nucleotide polymorphisms (SNPs) in the genes coding for critical enzymes and receptors involved in the melatonin pathway. A total of 590 subjects (193 MS patients and 397 healthy controls) were genotyped for seven SNPs in four genes including tryptophan hydroxylases (TPH)1 and 2, arylalkylamine N-acetyltransferase (AANAT) and melatonin receptor 1B (MTNR1B). An overrepresentation of T allele carriers of a functional polymorphism (G-703T, rs4570625) in the promoter region of TPH2 gene was observed in the progressive MS subtypes. The haplotype rs4570625-rs10506645TT of TPH2 gene was associated with the risk of severe disability in primary progressive MS (PPMS), while haplotype rs4570625-rs10506645TC appeared to be protective against disability in secondary progressive MS (SPMS). In the MTNR1B gene, the haplotype rs10830963-rs4753426GC was associated with the risk of SPMS, whereas another haplotype rs10830963-rs4753426GT showed an association with the risk of PPMS. These data showing the association of polymorphisms in the TPH2 and MTNR1B genes with the progressive subtypes of MS and disability suggest dysregulation in melatonin pathway. Melatonin pathway seems to be involved in disease progression, and therefore its potential effects in overcoming MSrelated neurodegeneration may be worth evaluating in future clinical trials.
Vitamin D receptor activation with paricalcitol can modulate the transcription of renin-angiotens... more Vitamin D receptor activation with paricalcitol can modulate the transcription of renin-angiotensin system components in the surgical 5/6 nephrectomy rat model (5/6 NX) of chronic renal insufficiency. We tested the hypothesis whether dietary modification of phosphate influences kidney renin-angiotensin system gene expression at the mRNA level in 5/6 NX rats. Fifteen weeks after surgery, rats were given control diet (0.3% calcium, 0.5% phosphate), phosphate-lowering diet (3% calcium as carbonate) or high-phosphate diet (1.5%) for 12 weeks. Sham-operated rats were on control diet. Blood pressure, plasma phosphate, parathyroid hormone, glomerulosclerosis, tubulointerstitial damage, and FGF-23 were increased in remnant kidney rats, whereas creatinine clearance was decreased. Phosphate, parathyroid hormone, glomerulosclerosis, tubulointerstitial damage, and FGF-23 were further elevated by the high-phosphate diet, but were reduced by the phosphate-lowering diet. Plasma calcium was increased with the phosphate-lowering diet and decreased with the high-phosphate diet. Remnant kidney rats on control diet showed upregulated kidney angiotensin-converting enzyme (ACE) and angiotensin (Ang) IV receptor (AT(4)) transcription, while ACE2, Ang II type 2 receptor and renin receptor transcription were downregulated in comparison with sham rats. Phosphate-lowering diet reduced whereas high-phosphate diet increased kidney ACE, and these effects were observed at both mRNA and protein levels. Dietary phosphate loading also resulted in lower AT(1a) gene transcription. Dietary phosphate loading was associated with elevated kidney ACE expression, increased tissue damage and lower AT(1a) transcription in 5/6 NX rats. Phosphate binding with 3% calcium carbonate had opposite effects on ACE and kidney damage.
Catecholamines and other catecholic compounds have opposite effects on the cyclooxygenase and 5-l... more Catecholamines and other catecholic compounds have opposite effects on the cyclooxygenase and 5-lipoxygenase pathways of arachidonic acid metabolism in human polymorphonuclear leukocytes and whole blood in vitro. The hypothesis that high levels of adrenaline, found e.g. in myocardial infarction, are involved in the regulation of arachidonic acid metabolism was tested. Adrenaline (0.1 micrograms/kg per min for 45 min and thereafter 0.2 micrograms/kg per min for 15 min) was infused to healthy male volunteers to mimic relationships between high levels of adrenaline and arachidonic acid metabolism in myocardial infarction. Adrenaline infusion increased Ca ionophore A23187-induced TXB2 formation in whole blood. The effect was smaller when spontaneous clotting was used as a stimulus. Urinary 11-dehydro-TXB2 excretion, an indicator of total in vivo thromboxane synthesis, increased twofold. Adrenaline infusion decreased both LTB4 and LTE4 synthesis in A23187-stimulated whole blood. These results demonstrate that high levels of adrenaline influence the cyclooxygenase and 5-lipoxygenase pathways of arachidonic acid metabolism differentially in man.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society
Functional and morphological changes of blood vessels in cyclosporine A (CsA)-induced hypertensio... more Functional and morphological changes of blood vessels in cyclosporine A (CsA)-induced hypertension and nephrotoxicity were studied in spontaneously hypertensive rats (SHR). The role of the L-arginine-nitric oxide (NO) pathway and the importance of oxidative stress in CsA toxicity were also assessed. SHR (7-8 week old) on a high-sodium diet were treated with CsA (5 mg kg(-1) d(-1) s.c.) for 6 weeks. A proportion of the rats were treated concomitantly with the NO precursor L-arginine (1.7 g kg(-1)d(-1) p.o.). CsA elevated blood pressure and caused renal dysfunction and morphological nephrotoxicity. CsA also impaired mesenteric and renal arterial function and caused structural damage to intrarenal and extrarenal small arteries and arterioles. Medial atrophy of the mesenteric resistance vessels and decreased viability of smooth muscle cells of the thoracic aorta were observed. Renal and arterial damage was associated with the presence of inflammatory cells. CsA did not affect markers of...
Journal of Chromatography B: Biomedical Sciences and Applications, 1984
Thin-layer chromatography (TLC) is widely used for the separation and identification of a number ... more Thin-layer chromatography (TLC) is widely used for the separation and identification of a number of arachidonic acid metabolites. There are descriptions of many TLC methods by which a variety of prostanoids can be separated [l--8].
Obstructive sleep apnoea (OSA) carries an increased risk of ischaemic stroke, but the underlying ... more Obstructive sleep apnoea (OSA) carries an increased risk of ischaemic stroke, but the underlying mechanism is not clear. As right-to-left shunting can occur through a patent foramen ovale (PFO) during periods of apnoea, we investigated nocturnal changes in fibrinolytic activity and platelet function in subjects who had OSA with or without PFO and in controls. We determined plasminogen activator inhibitor 1 (PAI-1) activity and antigen and platelet activation parameters. The severity of OSA was verified by polygraphy and PFO was detected by ear oximetry. We found a higher PAI-1 activity and antigen and a lower ratio of 2,3-dinor-PGF(1α) to 2,3-dinor-TXB(2) in the subjects with OSA than in the controls. Linear regression analysis showed the apnoea-hypopnoea index (β-coefficient, 0.499; P = 0.032) and PFO (β-coefficient, 0.594; P = 0.015) to be associated independently with PAI-1 activity in the morning, while the increment in PAI-1:Ag from evening to morning was significantly associat...
Prostaglandins, leukotrienes, and essential fatty acids, 2003
Our purpose was to determine urinary 9 alpha,11 beta-prostaglandin F2, the primary metabolite of ... more Our purpose was to determine urinary 9 alpha,11 beta-prostaglandin F2, the primary metabolite of prostaglandin D2, in pregnancies at high risk for hypertensive disorders and the effect of acetylsalicylic acid on 9 alpha,11 beta-prostaglandin F2. Ninety high risk women were randomised to acetylsalicylic acid and placebo groups at 12-14 weeks of gestation, with 43 women in both groups followed up successfully. 9 alpha,11 beta-prostaglandin F2 was determined at baseline, at 24-26, and at 32-34 weeks of gestation. Fifteen normotensive non-pregnant women, 17 normotensive pregnant women at 12-14, and 15 at 30-34 weeks of gestation served as controls. Urinary 9 alpha,11 beta-prostaglandin F2 was significantly higher in pregnant women at 12-14 weeks of gestation as compared to non-pregnant women. High risk pregnancies had higher 9 alpha,11 beta-prostaglandin F2 as compared to normotensive pregnancies at 12-14, and at 30-34 weeks of gestation. Urinary 9 alpha,11 beta-prostaglandin F2 increas...
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2000
Smoking is an important risk factor for respiratory and cardiovascular diseases. The role of nume... more Smoking is an important risk factor for respiratory and cardiovascular diseases. The role of numerous chemical, partly uncharacterised compounds existing in tobacco smoke is not known. (-)-Nicotine, its stereoisomer (+)-nicotine and main metabolite cotinine are biologically active compounds influencing e.g. catecholamine and eicosanoid systems. The precise mechanisms are not well known. The purpose of the present study consisting of a PhD thesis (11) and five original papers was to investigate the in vitro effects of nicotine isomers and cotinine on eicosanoid production in polymorphonuclear leukocytes, platelets and whole blood in vitro, and to clarify the effects of smoking without and with nicotine substitution on eicosanoid production in vivo and ex vivo. It was found that all the tested compounds modulated blood cell eicosanoid synthesis. Nicotine isomers and cotinine increased PGE2 but decreased TXB2, LTB4 and LTE4 synthesis in vitro. Eicosanoid synthesis in vivo and ex vivo w...
To compare the effects of unreamed and reamed intramedullary nailing on the systemic production o... more To compare the effects of unreamed and reamed intramedullary nailing on the systemic production of prostacyclin and thromboxane A2 as assessed, respectively, by determinations of urinary 2,3-dinor-6-ketoprostaglandin F1alpha and 11-dehydrothromboxane B2 excretion. Ten otherwise healthy patients with closed and simple tibial shaft fractures were treated with unreamed intramedullary nailing, and 10 otherwise healthy patients with closed and simple tibial shaft fractures were treated with reamed intramedullary nailing. Urine was collected preoperatively and during the next 5 postoperative days. The samples were stored at -70 degrees C until assayed at the end of the study. In the unreamed group, urinary 2,3-dinor-6-ketoprostaglandin F1alpha and 11-dehydrothromboxane B2 excretion remained stable and at a significantly lower levels compared with the reamed group during the entire study period (p < 0.021). In the reamed group, the alteration in urinary 2,3-dinor-6-ketoprostaglandin F1a...
We investigated the effects of nicotine and cotinine (0.5 nM-0.5 mM) on prostaglandin E2 and leuk... more We investigated the effects of nicotine and cotinine (0.5 nM-0.5 mM) on prostaglandin E2 and leukotriene B4 production in human polymorphonuclear leukocytes and on thromboxane B2 formation in human platelet-rich plasma, stimulated by calcium ionophore A23187. Nicotine and cotinine dose-dependently increased prostaglandin E2 synthesis in polymorphonuclear leukocytes from 25% (0.5 nM) up to nearly four-fold (0.5 mM). In concentrations found in the plasma of smokers, nicotine and cotinine increased prostaglandin E2 production by 33% (50 nM) and 50% (500 nM), respectively. Nicotine and cotinine equipotentially reduced both leukotriene B4 production in polymorphonuclear leukocytes and thromboxane B2 production in platelet rich plasma, the inhibition increasing from 20% (0.5 nM) to 60% (0.5 mM). The stimulation of prostaglandin E2 and inhibition of leukotriene B4 and thromboxane B2 production by nicotine and cotinine may due to the pyridine moiety that these compounds have in common.
Catecholamines (adrenaline, dopamine, isoprenaline, noradrenaline) and caffeic acid (catecholic c... more Catecholamines (adrenaline, dopamine, isoprenaline, noradrenaline) and caffeic acid (catecholic compound without adrenergic receptor activity) decreased leukotriene (LT)B4 synthesis in A23187-stimulated human whole blood. Salbutamol, a non-catecholic beta 2-adrenergic agonist, did not influence LTB4 synthesis. Catecholamines stimulated thromboxane (TX)B2 synthesis with a concomitant inhibition of LTB4 synthesis; caffeic acid and salbutamol did not stimulate TXB2 synthesis. These results, obtained in A23187-stimulated whole blood, which also takes into account the complex interaction between different cell types, are similar to our previous results with polymorphonuclear leukocytes. Catecholamines show an opposite effect on lipoxygenase and cyclooxygenase pathways, which may give rise to a marked change in LT/TX ratio in physiological or pathological conditions where sufficient concentrations of catecholamines are present.
Our aim was to compare the effects of calcium carbonate and sevelamer-HCl treatments on calcium-p... more Our aim was to compare the effects of calcium carbonate and sevelamer-HCl treatments on calcium-phosphate metabolism and renal function in 5/6 nephrectomized (NX) rats so that long-term disease progression preceded the treatment. After 15-week progression, calcium carbonate (3.0%), sevelamer-HCl (3.0%), or control diets (0.3% calcium) were given for 9 weeks. Subtotal nephrectomy reduced creatinine clearance (−40%), plasma calcidiol (−25%), and calcitriol (−70%) and increased phosphate (+37%), parathyroid hormone (PTH) (11-fold), and fibroblast growth factor-23 (FGF-23) (4-fold). In NX rats, calcium carbonate diet increased plasma (+20%) and urinary calcium (6-fold), reduced plasma phosphate (−50%) and calcidiol (−30%), decreased creatinine clearance (−35%) and FGF 23 (−85%), and suppressed PTH without influencing blood pH. In NX rats, sevelamer-HCl increased urinary calcium (4-fold) and decreased creatinine clearance (−45%), PTH (−75%), blood pH (by 0.20 units), plasma calcidiol (−40%), and calcitriol (−65%). Plasma phosphate and FGF-23 were unchanged. In conclusion, when initiated after long-term progression of experimental renal insufficiency, calcium carbonate diet reduced plasma phosphate and FGF-23 while sevelamer-HCl did not. The former induced hypercalcemia, the latter induced acidosis, while both treatments reduced vitamin D metabolites and deteriorated renal function. Thus, delayed initiation influences the effects of these phosphate binders in remnant kidney rats.
Nitric Oxide and Free Radicals in Peripheral Neurotransmission, 2000
... The reperfusion period following transient coronary occlusion is associated with accumulation... more ... The reperfusion period following transient coronary occlusion is associated with accumulation of neutrophils, which probably contribute to myocardial damage (Brady et aI., 1992; Tsao and Lefer, 1990). ... Br.l Urol. 78:257-261. Brady, AJ, Williams, EM., and Williams, TJ 1992. ...
Prostaglandins, Leukotrienes and Essential Fatty Acids, 2001
It has previously been shown that leukotriene E4 production is increased both in acute and chroni... more It has previously been shown that leukotriene E4 production is increased both in acute and chronic lower limb ischaemia.The aim of this study was to measure the effect of revascularisation on leuktriene E4 excretion in chronic lower limb ischaemia. Revascularisation did not affect significantly on leukotriene E4 excretion (preop. 34.9þ7. 1pg/mg creatinine, postop. 24.5þ4.7 pg/mg creatinine, n=10, P50.238 ).We suggest that the enhanced leukotriene E4 production continues after revascularisation which may have a therapeutical implication.
Prostaglandins, Leukotrienes and Essential Fatty Acids, 2003
Our purpose was to determine urinary 9a;11b-prostaglandin F 2 , the primary metabolite of prostag... more Our purpose was to determine urinary 9a;11b-prostaglandin F 2 , the primary metabolite of prostaglandin D 2 , in pregnancies at high risk for hypertensive disorders and the effect of acetylsalicylic acid on 9a;11b-prostaglandin F 2 .
We have previously demonstrated that adrenaline infusion increases the thromboxane/leukotriene (T... more We have previously demonstrated that adrenaline infusion increases the thromboxane/leukotriene (TX/LT) ratio in whole blood in healthy volunteers. The aim of the present study was to see whether other catecholamines -noradrenaline and dopamine -are also capable of modulating arachidonic acid (AA) metabolism in man. Low doses of noradrenaline (0.025 gg/kg/min) and dopamine (3.0 g/kg/min), which did not change hemodynamics, were infused for 60m in into healthy male volunteers. Both dopamine and noradrenaline decreased TX synthesis stimulated by spontaneous clotting, but no remarkable effect was seen when calcium ionophore A23187 was used as a stimulus. Dopamine but not noradrenaline increased prostaglandin E 2 (PGE2) synthesis in A23187-stimulated whole blood. They both marginally decreased LTB4 formation in A23187-stimulated whole blood. The findings indicate that not only adrenaline but also noradrenaline and dopamine modulate AA metabolism in man.
Naunyn-Schmiedeberg's Archives of Pharmacology, 2001
This study investigated the effects of smoking cessation with and without nicotine substitution o... more This study investigated the effects of smoking cessation with and without nicotine substitution on the excretion of major urinary metabolites of thromboxane A 2 and prostacyclin, 11-dehydrothromboxane B 2 and 2,3-dinor-6-ketoprostaglandin F 1α , respectively, as well as on the excretion of leukotriene E 4 in man. Urine samples were obtained from 20 healthy non-smoking controls and from 60 healthy smoking volunteers before, and 3, 7 and 14 days after smoking cessation. Fifteen smokers quit smoking without nicotine substitution, 15 used nicotine chewing gum and 30 used nicotine patches as a substitution therapy. Urinary thiocyanate as well as cotinine and trans-3'-hydroxycotinine excretions were used as compliance and nicotine substitution indicators.
In this study we investigated the relationship between melatonin pathway and multiple sclerosis (... more In this study we investigated the relationship between melatonin pathway and multiple sclerosis (MS) in a high-risk Finnish population by studying the single nucleotide polymorphisms (SNPs) in the genes coding for critical enzymes and receptors involved in the melatonin pathway. A total of 590 subjects (193 MS patients and 397 healthy controls) were genotyped for seven SNPs in four genes including tryptophan hydroxylases (TPH)1 and 2, arylalkylamine N-acetyltransferase (AANAT) and melatonin receptor 1B (MTNR1B). An overrepresentation of T allele carriers of a functional polymorphism (G-703T, rs4570625) in the promoter region of TPH2 gene was observed in the progressive MS subtypes. The haplotype rs4570625-rs10506645TT of TPH2 gene was associated with the risk of severe disability in primary progressive MS (PPMS), while haplotype rs4570625-rs10506645TC appeared to be protective against disability in secondary progressive MS (SPMS). In the MTNR1B gene, the haplotype rs10830963-rs4753426GC was associated with the risk of SPMS, whereas another haplotype rs10830963-rs4753426GT showed an association with the risk of PPMS. These data showing the association of polymorphisms in the TPH2 and MTNR1B genes with the progressive subtypes of MS and disability suggest dysregulation in melatonin pathway. Melatonin pathway seems to be involved in disease progression, and therefore its potential effects in overcoming MSrelated neurodegeneration may be worth evaluating in future clinical trials.
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Papers by Asko Riutta