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  • Articles  (94)
  • 2000-2004  (22)
  • 1990-1994  (46)
  • 1975-1979  (26)
  • Medicine  (93)
  • Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics  (1)
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  • Articles  (94)
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  • 1
    ISSN: 1432-1440
    Keywords: Aldosteron ; Renin-Angiotensin ; Essentielle Hypertonie ; Aldosterone ; Renin-angiotensin ; Essential hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In essential hypertension mean basal (supine) and stimulated plasma renin activity (2 h upright posture +40 mg furosemide intraveneously) decreased progressively with age. No significant differences were observed in renin levels between male and female patients. With increasing age mean basal (supine) plasma aldosterone remained almost unchanged in females, whereas in males a slight increase was found. However, in the comparable age-groups no significant sexrelated differences were obtained. In female patients changes in mean stimulated plasma aldosterone with increasing age paralleled those of plasma renin activity, whereas in males this relationship was less obvious: only a slight age-related decline in stimulated aldosterone levels was observed and significantly lower plasma aldosterone concentrations in male than in female hypertensives of the younger age-groups (〈40 years) were found. The results indicate that in essential hypertension with increasing age dissociation between plasma aldosterone and plasma renin activity occurred. Furthermore, the described alterations in adrenal aldosterone release are more pronounced in male than in female patients.
    Notes: Zusammenfassung Bei Patienten mit essentieller Hypertonie fiel sowohl die basale als auch die stimulierte Plasmareninaktivität (2 h aktive Orthostase +40 mg Furosemid intravenös) mit zunehmendem Lebensalter kontinuierlich ab. Signifikante Unterschiede zwischen Männern und Frauen fanden sich nicht. Die mittlere basale Plasmaaldosteronkonzentration zeigte bei weiblichen Patienten keine altersabhängigen Veränderungen, während bei männlichen Patienten ein leichter Anstieg festgestellt werden konnte. Allerdings ergaben sich hier keine signifikanten Geschlechtsunterschiede in den vergleichbaren Altersgruppen. Die mittlere stimulierte Plasmaaldosteronkonzentration zeigte bei Frauen mit zunehmendem Alter ein der Plasmareninaktivität paralleles Verhalten, während dies bei Männern weit weniger ausgeprägt war; so fand sich bei männlichen Patienten nur ein geringer Abfall der mittleren stimulierten Plasmaaldosteronkonzentration mit dem Alter und die Aldosteronspiegel waren in den jüngeren Altersgruppen (〈40 Jahre) signifikant niedriger als bei weiblichen Patienten. Die Ergebnisse zeigen, daß bei Patienten mit essentieller Hypertonie mit zunehmendem Lebensalter eine Dissoziation zwischen Plasmaaldosteron und Plasmareninaktivität auftritt, wobei dieser Befund bei Männern deutlicher ausgeprägt ist als bei Frauen.
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  • 2
    ISSN: 1432-1440
    Keywords: Plasma-Renin-Aktivität ; Propranolol ; Prindolol ; Plasma renin activity ; propranolol ; prindolol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary To investigate the effect of propranolol and prindolol on renin secretion plasma renin activity (PRA) was determined overnight at short-time intervals in 10 sodium-restricted normal supine subjects. 4 of them were on a 4-days medication with propranolol, 3 were treated with prindolol and 3 were used as control group. In normal controls renin was secreted episodically and showed characteristic night-day variations. Both in propranolol and in prindolol-treated subjects secretory episodes in renin secretion either did not occur or were less frequent than in normal controls. With one exception night-day variations in renin secretion were not observed. Mean PRA values were significantly lower than in the control group (p〈0.001). Our results show that both propranolol and prindolol lower PRA and eliminate or reduce the frequency of secretory episodes. It is concluded that the sympathetic nervous system plays an important role in regulating night-day variations and short-time fluctuations of renin secretion in normal supine man.
    Notes: Zusammenfassung Um den Effekt von Propranolol und Prindolol auf die Reninsekretion zu untersuchen, wurde unter natriumarmer Ernährung bei 10 liegenden Normalpersonen in kurzen Zeitabständen über Nacht die Plasma-Renin-Aktivität (PRA) bestimmt. 4 Personen standen unter einer 4tägigen Behandlung mit Propranolol, 3 wurden über denselben Zeitraum mit Prindolol behandelt und 3 Personen dienten als Kontrollgruppe. Bei Normalpersonen zeigte Renin sowohl eine episodische Sekretion als auch einen typischen Nacht-Tag-Rhythmus. Unter Propranolol und Prindolol wurden Sekretionsepisoden des Renins entweder nicht beobachtet oder traten seltener auf. Eine Nacht-TagSchwankung der Reninsekretion war mit einer Ausnahme nicht zu beobachten. Unter beiden Betablockern war die mittlere PRA signifikant niedriger als bei Kontrollpersonen (p〈0.001). Unsere Ergebnisse zeigen, daß Propranolol und Prindolol die Renin-Aktivität senken und entweder die episodische Reninsekretion aufheben oder zu einer Frequenzabnahme der Sekretionsepisoden führen. Unsere Resultate erlauben die Schlußfolgerung, daß das sympathische Nervensystem eine bedeutende Rolle in der Steuerung der Nacht-Tag-Rhythmik und in der Regulation der Kurz-ZeitSchwankungen der Reninsekretion spielt.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 57 (1979), S. 863-873 
    ISSN: 1432-1440
    Keywords: Renovascular hypertension ; Renal venous renin activity ; Effect of surgery ; Renovaskuläre Hypertonie ; Nierenvenenreninaktivität ; Operationserfolg
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung In der vorliegenden Untersuchung wurde das postoperative Blutdruckverhalten bei 35 Patienten mit renovaskulärer Hypertonie untersucht: 17 Patienten mit fibromuskulärer Dysplasie (FMD) und 18 mit arteriosklerotischen Gefäßwandveränderungen (ASS). Patienten mit FMD waren im Mittel jünger (31,8 Jahre), zeigten eine kürzere Hypertonieanamnese (1,8 Jahre) und waren prävalent weiblich (82%), während Patienten mit ASS deutlich älter waren (48,2 Jahre), eine längere Hypertoniedauer (2,6 Jahre) zeigten und bevorzugt männlich (78%) waren. In beiden Gruppen zeigte das intravenöse Pyelogramm einen vergleichbar hohen Anteil positiver Befunde (FMD=64%, ASS=61%). Postoperativ waren in der Gruppe mit FMD 47% (n=8) geheilt, 47% (n=8) gebessert und nur 6% (n=1) der Patienten geringgradig gebessert. Die vergleichbaren Werte für die Gruppe mit ASS betrugen 28, 55 und 17%. Für das Gesamtkollektiv war folglich ein guter Operationserfolg (geheilt und gebessert) in 88,5% der Fälle zu beobachten. Patienten mit ASS und postoperativ nur geringgradiger Besserung (n=3) zeigten eine auffallend lange Hypertonieanamnese (7,0±1,4 Jahre). Bei allen Patienten wurde präoperativ die seitengetrennte Bestimmung der Renin-Aktivität (PRA) im Nierenvenenblut durchgeführt und aus den Werten die PRA-Quotienten (PRA betroffene/nicht betroffene Seite) errechnet. Bei 27 Patienten wurde die Bestimmung 15 und 30 min nach intravenöser Stimulation mit 40 mg Furosemid wiederholt. PRA-Quotienten von ≧1,5 wurden als signifikant bezeichnet. Bei 31 Patienten mit einseitiger renovaskulärer Hypertonie wurde die Höhe des PRA-Quotienten zum postoperativen Blutdruckverhalten korreliert. Dabei zeigte sich zwischen der Gruppe der postoperativ Geheilten und der der postoperativ Gebesserten kein signifikanter Unterschied im mittleren PRA-Quotienten. Ferner ließen sich für das Gesamtkollektiv der 31 Patienten mit einseitiger renovaskulärer Hypertonie unter Ausgangs- und Stimulationsbedingungen keine signifikanten Korrelationen zwischen Höhe der PRA-Quotienten und postoperativem Blutdruckabfall ermitteln. Unsere Ergebnisse unterstützen nicht die weit verbreitete Ansicht, daß sich die seitengetrennte Bestimmung der PRA im Nierenvenenblut als Parameter für den zu erwartenden Operationserfolg bei Patienten mit einseitiger renovaskulärer Hypertonie eignet. Die Methode kann deshalb nach unserer Ansicht nicht mehr als obligater Bestandteile der präoperativen Diagnostik der renovaskulären Hypertonie empfohlen werden.
    Notes: Summary In the present study the effect of surgery on blood pressure was investigated in 35 patients with renovascular hypertension: 17 patients with fibromuscular hyperplasia (FMD) and 18 with atherosclerosis (ASS) of the renal artery. Patients with FMD were younger (31,8 years), showed a shorter duration of hypertension (1.8 years) and were prevalently female (82%), whereas patients with ASS were markedly older (48.2 years), showed a longer duration of hypertension (2.6 years) and were most often male (78%). In both groups of patients the intravenous urogram was positive in a comparable high percentage (FMD=64%, ASS=61%). Following surgical intervention 47% (n=8) of the 17 patients with FMD were cured, 47% (n=8) were improved and only 6% (n=1) showed insufficient reduction of blood pressure values. In ASS the respective values were 28, 55 and 17%. Consequently a good effect of surgery (cured and improved) was observed in 88.5% of all patients. Patients with ASS who failed to respond to surgery (n=3) showed a remarkable long duration of hypertension (7.0±1.4 years). Plasma renin activity (PRA) was determined preoperatively in both renal veins in all 35 patients. From these values the PRA-ratio (PRA affected/unaffected side) was calculated. In 27 patients PRA determinations were repeated following (15 and 30 min) intravenous injection of 40 mg furosemide. PRA-ratios of ≧1.5 were considered to be significant. In 31 patients with unilateral renovascular hypertension PRA-ratios were correlated to the postoperative blood pressure reduction. No significant differences in mean PRA-ratios were observed between cured and improved patients. Furthermore, for the total group of 31 patients no significant correlations were obtained between PRA-ratios and postoperative blood pressure reduction. Our results do not support the widespread opinion that PRA determinations in both renal veins are useful to predict the effect of surgery in patients with unilateral renovascular disease. Therefore, from our experience this method should not be recommended as obligatory in the diagnostic work-up of renovascular hypertension.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 53 (1975), S. 391-393 
    ISSN: 1432-1440
    Keywords: Aldosteron ; Renin ; Spironolacton ; Primärer Aldosteronismus ; Aldosterone ; renin ; spironolactone ; aldosteronism primary
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In a patient suffering from Conn's syndrome analysis of short-time fluctuations of plasma aldosterone, plasma cortisol and plasma renin activity were performed before and after a 9-months therapy period with spironolactone. Under the former conditions aldosterone was secreted episodically and a highly significant correlation was found between plasma aldosterone and plasma cortisol (r=0.817,p〈0.001) while plasma renin activity was undetectable (〈0.16 ng/ml/3 hr). Following a 9-months therapy with spironolactone episodic secretion of aldosterone and the significant correlation between aldosterone and cortisol persisted (r=0.819,p〈0.001) in the presence of an abnormally high plasma renin activity. First, when the secretion of ACTH was suppressed by dexamethasone a weak correlation was found between renin activity and aldosterone (r=0.517,p〈0.05). Our results show that both before and after a 9-months therapy with spironolactone episodic aldosterone release of an aldosterone producing adrenal adenoma was mediated through ACTH and that endogeneous angiotensin II had no or only little influence.
    Notes: Zusammenfassung Bei einer Patientin mit Conn Syndrom wurden vor und nach einer 9-monatigen Behandlung mit Spironolacton Plasma-Aldosteron, Plasma-Cortisol und Plasma-Renin-Aktivität in kurzen Zeitabständen bestimmt. Vor Behandlung wurde Plasma-Aldosteron episodisch sezerniert; es fand sich eine hochsignifikante Korrelation zwischen Plasma-Aldosteron und Plasma-Cortisol (r=0.817,p〈0.001). Die Plasma-Renin-Aktivität lag ständig unterhalb des aufdeckbaren Meßbereiches (〈0,16 ng/ml/3 h). Nach 9-monatiger Behandlung mit Spironolacton war in Gegenwart einer deutlich über der Norm erhöhten Plasma-Renin-Aktivität sowohl eine episodische Sekretion des Plasma-Aldosterons als auch eine signifikante Korrelation zwischen Plasma-Aldosteron und Plasma-Cortisol nachweisbar (r=0.819,p〈0.001). Erst nach Suppression der ACTH-Sekretion durch Dexamethason fand sich eine schwache K orrelation zwischen Renin-Aktivität und Aldosteron (r=0.517,p〈0.05). Unsere Ergebnisse zeigen, daß sowohl vor als auch nach 9-monatiger Behandlung mit Spironolacton die episodische Sekretion des Plasma-Aldosterons bei einer Patientin mit einem aldosteronproduzierenden Nebennierenrindenadenom durch ACTH gesteuert wird. Demagegenüber besitzt endogenes Angiotensin II keinen oder einen nur geringen Einfluß auf die Aldosteron-Sekretion.
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  • 5
    ISSN: 1432-1440
    Keywords: Cushing-Syndrom ; Hypertonie ; Renin-Aktivität ; Aldosteronismus ; Cushing's syndrome ; Hypertension ; Renin activity ; Aldosteronism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary To investigate the role of the renin angiotensin system in the pathogenesis of hypertension in Cushing's syndrome two patients with hypercorticism were infused with 20 mg saralasin (1-sar-8-alaangiotensin II) over a period of 30 minutes under constant blood pressure control. In addition, one patient with primary aldosteronism, an established form of mineralocorticoid hypertension, served as control. Neither in the two patients with Cushing's syndrome nor in the patient with primary aldosteronism could a blood pressure lowering effect of saralasin be observed. In the two patients with hypercorticism both renin activity and plasma aldosterone increased during saralasin infusion. The patient with primary aldosteronism only showed a weak increase in plasma aldosterone concentration. These results seem to exclude an important role of the renin angiotensin system in the pathogenesis of hypertension in Cushing's syndrome. The unresponsiveness of elevated blood pressure to saralasin in the two patients with hypercorticism and in the patient with primary aldosteronism indirectly supports the assumption that in patients with Cushing's syndrome increased mineralocorticoid activity may be the main factor in the pathogenesis of hypertension.
    Notes: Zusammenfassung Um die Bedeutung des Renin-Angiotensin Systems in der Pathogenese der Hypertonie bei Cushing-Syndrom zu untersuchen, wurden bei 2 Patienten mit Hyperkortizismus 20 mg Saralasin (1-Sar-8-Ala-Angiotensin II) über einen Zeitraum von 30 min unter ständiger Blutdruckkontrolle infundiert. Zusätzlich diente ein Patient mit primärem Aldosteronismus, einer etablierten Form von Mineralokortikoidhochdruck, als Kontrolle. Weder bei den 2 Patienten mit Cushing-Syndrom noch bei dem Patienten mit primärem Aldosteronismus ließ sich ein blutdrucksenkender Effekt des Saralasins nachweisen. Die beiden Patienten mit Hyperkortizismus zeigten unter Saralasin sowohl einen Anstieg der Renin-Aktivität als auch des Plasmaaldosterons. Bei dem Patienten mit primärem Aldosteronismus ließ sich nur ein geringgradiger Anstieg der Plasmaaldosteronkonzentration nachweisen. Diese Ergebnisse sprechen gegen eine wichtige Rolle des Renin-Angiotensin Systems in der Pathogenese der Hypertonie bei Cushing-Syndrom. Die Unbeeinflußbarkeit des Hochdrucks durch Saralasin bei den beiden Patienten mit Hyperkortizismus und dem Patienten mit primärem Aldosteronismus stützen indirekt die Annahme, daß bei Patienten mit Cushing-Syndrom eine erhöhte Mineralokortikoidaktivität der Hauptfaktor in der Pathogenese der Hypertonie ist.
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  • 6
    Electronic Resource
    Electronic Resource
    350 Main Street , Malden , MA 02148-5020 , USA and 9600 Garsington Road , Oxford OX4 2XG , England . : Blackwell Science Inc
    Journal of cardiac surgery 19 (2004), S. 0 
    ISSN: 1540-8191
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract  Background: The object was to evaluate the long-term effectiveness of strategies for managing the aortic root and distal aorta in type A dissections. Methods: From 1990 to 1999, 50 patients (32 men (64.07%); 18 women, (36.0%); mean age 57.4 ± 11.1 years) underwent operation for ascending aortic dissection. Surgical strategies included aortic root replacement with a composite graft (21/50; 42.0%), valve replacement with supracoronary ascending aortic graft (3/50, 6%), and valve preservation or repair (26/50; 52.0%). Results: Overall hospital mortality rate was 18.0%. Follow-up was completed for 47 patients (94.0%) and ranged from 1 month to 10.5 years (mean 28.8 months). Actuarial survival for patients discharged from the hospital was 84% at 1 year, 75% at 5 years, and 66% at 10 years. There was no significant difference between the various procedures regarding mortality, neurological complications, long-term survival, and proximal reoperations. The ascending aorta alone was replaced in 8 of 50 patients (16%), ascending and hemiarch in 30 of 50 patients (60%), and arch and proximal descending aorta in 12 of 50 patients (24%). Hospital mortality (11.5%, 20.0%, and 16.7%, respectively; p 〉 0.05) and 5- and 10-year survival (p 〉 0.05) were not statistically dependent on the extension of the resection distally. Residual distal dissection was not associated with a decrease in late survival. With regard to emergency surgery (36/50) there was no significant difference in hospital mortality (p 〉 0.05) and 5-year survival (p 〉 0.05) between those who had undergone coronary angiography (19/36; 52.8%) on the day of surgery with those who had not (17/36; 47.2%). Conclusions: Preservation or repair of the aortic valve can be recommended in the majority of patients with type A dissection. Distal extension of the resection does not increase surgical risk. Residual distal dissection does not decrease late survival. Preoperative coronary angiography may not affect survival in patients undergoing emergency surgery. (J Card Surg 2004;19:240-245)
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  • 7
    Electronic Resource
    Electronic Resource
    350 Main Street , Malden , MA 02148-5020 , USA and 9600 Garsington Road , Oxford OX4 2XG , England . : Blackwell Science Inc
    Journal of cardiac surgery 19 (2004), S. 0 
    ISSN: 1540-8191
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract  Background: The Edwards MIRA™ mechanical heart valve is designed to optimize hemodynamics, reduce thrombogenicity, and avoid mechanical failure with a special hinge mechanism. The purpose of the study was to investigate the clinical performance and postoperative hemodynamic results of the first European patients receiving Edwards MIRA™ mechanical heart valves. Methods: From March 1998 to March 1999 a total of 54 Edwards MIRA™ valves model numbers 3600 (aortic, n = 44) and 9600 (mitral, n = 10) were implanted in 52 (36 male, 16 female; mean age 61 ± 10.1 years) consecutive patients undergoing mechanical valve replacement in a prospective study. Follow-up of the patients including physical examination, ECG, blood tests, and Doppler were performed prior to discharge, at 6 months, at 1 year, and at least 2 years postoperatively. Results: Through October 2001 a total of 172 follow-up examinations were completed (51 patients at discharge, 46 patients at 6 months, 43 patients at 12 months, 32 patients at 2 years or beyond). All patients were in NYHA class I and II at the 6-month and 2+-year follow-up. All the patients stated an improved quality of life. Hospital mortality was 1.9%. There were no complications related to anticoagulation. Mean international normalized ratio at 6 months was 3.2 (range 1.9 to 4.3); lactate dehydrogenase was slightly increased with 264 ± 103 U/L on average (normal value 80 to 240 U/L). No signs of valvular dysfunction or paravalvular leakage were observed. Mean pressure gradients were related to valve diameter: after mitral valve replacement (size 27, 29, 31 mm: 4.8, 3.2, 2.1 mmHg); after aortic valve replacement (size 19, 21, 23, 25 mm: 12.1, 13.1, 9.3, 8.2 mmHg). Conclusions: These preliminary data suggest good hemodynamic function and a low rate of valve-related complications of the Edwards-MIRA™ mechanical prosthesis. (J Card Surg 2004;19:226-231)
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  • 8
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Morphine-6-glucuronide (M6G) is a substrate of P-glycoprotein (P-gp), which forms an outward transporter at the blood–brain barrier. Inhibition of P-gp may therefore be expected to cause increased CNS uptake of M6G. We directly assessed the spinal concentrations of M6G and its antinociceptive effects in rats following pharmacological inhibition of P-gp. Spinal cord tissue concentrations of M6G were assessed by microdialysis with probes transversally implanted through the dorsal horns of the spinal cord at level L4. Ten rats received M6G intravenously (0.018 mg/kg loading dose plus 0.00115 mg/kg/min for an 8-h infusion), five of them together with PSC833 to inhibit P-gp (32-h infusion, starting 24 h before the addition of M6G). Antinociceptive effects were explored by means of formalin tests. After having obtained evidence for enhanced CNS uptake and antinociception of M6G in the presence of PSC833, additional behavioural experiments were performed in another 32 rats to assess the dose dependency of the antinociceptive effects of M6G either with or without PSC833 in comparison with both PSC833 alone and placebo. Inhibition of P-gp increased the M6G concentrations in the spinal cord approximately three-fold whereas the plasma concentrations were increased only by a factor of 1.4, which resulted in a more than doubled spinal cord/plasma concentration ratio (from 0.08 ± 0.03 for M6G alone to 0.17 ± 0.08 for M6G plus PSC833). Antinociceptive effects of M6G were significantly enhanced by inhibition of P-gp. Inhibition of P-gp alters the transport of M6G across the blood–brain barrier, resulting in enhanced spinal cord uptake and enhanced antinociception.
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  • 9
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Peripheral noxious stimuli have been shown to induce prostaglandin (PG) E2 release at the site of inflammation and in the spinal cord. The antiinflammatory and antinociceptive effects of cyclooxygenase-inhibiting drugs are thought to depend on the inhibition of PG synthesis. R-Flurbiprofen, however, does not inhibit cyclooxygenase activity in vitro but still produces antinociceptive effects. To find out whether R-flurbiprofen acts via inhibition of spinal PG release, concentrations of PGE2 and flurbiprofen in spinal cord tissue were assessed by microdialysis. The catheter was transversally implanted through the dorsal horns of the spinal cord at level L4. R- and S-flurbiprofen (9 and 27 mg kg-1, respectively) were administered intravenously 10-15 min before subcutaneous injection of formalin into the dorsal surface of one hindpaw. Flurbiprofen was rapidly distributed into the spinal cord with maximal concentrations after 30-45 min. Baseline PGE2 dialysate concentrations were 100.6 ± 6.4 pg ml-1 (mean ± SEM). After formalin injection they rose about threefold with a maximum of 299.4 ± 68.4 pg ml-1 at 7.5 min. After ∼ 1 h PGE2 levels returned to baseline. Both flurbiprofen enantiomers completely prevented the formalin-induced increase of spinal PGE2 release and reduced PGE2 concentrations below basal levels. S- and R-flurbiprofen at 9 mg kg-1 produced a minimum of 15.8 ± 5.2 and 27.7 ± 14.9 pg ml-1, respectively, and 27 mg kg-1S- and R-flurbiprofen resulted in 11.7 ± 1.7 and 9.3 ± 4.7 pg ml-1, respectively. PGE2 levels remained at the minimum up to the end of the observation period at 5 h. When 27 mg kg-1R-flurbiprofen was injected intravenously without subsequent formalin challenge, baseline immunoreactive PGE2 concentrations were not affected. S-Flurbiprofen (27 mg kg-1), however, led to a moderate reduction (∼40%). The data suggest that antinociception produced by R-flurbiprofen is mediated at least in part by inhibition of stimulated spinal PGE2 release and support the current view that increased spinal PGE2 release significantly contributes to nociceptive processing.
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  • 10
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Nociception evoked prostaglandin (PG) release in the spinal cord considerably contributes to the induction of hyperalgesia and allodynia. To evaluate the relative contribution of cyclooxygenase-1 (COX-1) and COX-2 in this process we assessed the effects of the selective COX-1 inhibitor SC560 and the selective COX-2 inhibitor celecoxib on formalin-evoked nociceptive behaviour and spinal PGE2 release. SC560 (10 and 20 mg/kg) significantly reduced the nociceptive response and completely abolished the formalin-evoked PGE2 raise. In contrast, celecoxib (10 and 20 mg/kg) was ineffective in both regards, i.e. the flinching behaviour was largely unaltered and the formalin-induced PGE2 raise as assessed using microdialysis was only slightly, not significantly reduced. This suggests that the formalin-evoked rapid PG release was primarily caused by COX-1 and was independent of COX-2. Mean free spinal cord concentrations of celecoxib during the formalin assay were 32.0 ± 4.5 nm, thus considerably higher than the reported IC50 for COX-2 (3–7 nm). Therefore, the lack of efficacy of celecoxib is most likely not to be a result of poor tissue distribution. COX-2 mRNA and protein expression in the spinal cord were not affected by microdialysis alone but the mRNA rapidly increased following formalin injection and reached a maximum at 2 h. COX-2 protein was unaltered up to 4 h after formalin injection. The time course of COX-2 up-regulation suggests that the formalin-induced nociceptive response precedes COX-2 protein de novo synthesis and may therefore be unresponsive to COX-2 inhibition. Considering the results obtained with the formalin model it may be hypothesized that the efficacy of celecoxib in early injury evoked pain may be less than that of unselective NSAIDs.
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