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Consequences of altered eicosanoid patterns for nociceptive processing in mPGES-1-deficient mice (2007)

Christian Brenneis Ovidiu Coste Ronald Schmidt Carlo Federico Angioni Laura Popp Rolf M. Nusing Wiebke Becker Klaus Scholich Gerd Geisslinger

Cyclooxygenase-2 (COX-2)-dependent prostaglandin (PG) E2 synthesis in the spinal cord plays a major role in the development of inflammatory hyperalgesia and allodynia. Microsomal PGE2 synthase-1 (mPGES-1) isomerizes COX-2-derived PGH2 to PGE2. Here, we evaluated the effect of mPGES-1-deficiency on the noci-ceptive behavior in various models of nociception that depend on PGE2 synthesis. Surprisingly, in the COX-2-dependent zymosan-evoked hyperalgesia model, the nociceptive behavior was not reduced in mPGES-1-deficient mice despite a marked decrease of the spinal PGE2 synthesis. Similarly, the nociceptive behavior was unaltered in mPGES-1-deficient mice in the formalin test. Importantly, spinal cords and primary spinal cord cells derived from mPGES-1-deficient mice showed a redirection of the PGE2 synthesis to PGD2, PGF2α and 6-keto-PGF1α (stable metabolite of PGI2). Since the latter prostaglandins serve also as mediators of noci-ception they may compensate the loss of PGE2 synthesis in mPGES-1-deficient mice.

short @nd sweet news : Nr. 10 (2007)

* Prof. Gerlach appointed to the Health Advisory Council * New professorship at the Institute for General Practice * Every-Error-Counts website revamped * Taking care of patients with chronic diseases * Error research: Study on safety culture planned * Online registration now possible for students * BMBF sponsors PRoMPT follow-up study

short @nd sweet news : Nr. 9 (2007)

* Change the Date: 1st Frankfurt General Practice Day * Summer Symposium of the Praxissiegel Foundation on July 6, 2007 * Revamp of the course "Introduction to Clinical Medicine" * Summer celebration for practice participants in the PRoMPTresearch project

kurz und kn@pp news : Nr. 8 [engl. Fassung] (2007)

* Advance Notice: 1st Frankfurt Ge-neral Practice Day * Tips on how to avoid errors * STERN-Leading article on high blood pressure in cooperation with the Institute * 2nd part of DEGAM chronic heart failure guideline - long version * Launch of the anonymous error circle! * Over 1,000 students trained in evidence based medicine * Research assistant wanted

kurz und kn@pp news : Nr. 10 (2007)

* Prof. Gerlach in den Sachverständigenrat Gesundheit berufen * Zusätzliche Professur im Institut für Allgemeinmedizin * Jeder-Fehler-zaehlt in neuem Design * Betreuung von Menschen mit chronischen Erkrankungen * Fehlerforschung: Studie zur Sicherheitskultur geplant * Online-Eintragung für Studierende jetzt möglich * BMBF fördert PRoMPT-Folgestudie

kurz und kn@pp news : Nr. 9 (2007)

* Terminänderung: 1. Frankfurter Tag der Allgemeinmedizin * Sommersymposium der Stiftung Praxissiegel e.V. am 6. Juli 2007 * Neukonzeption des Kurses "Einführung in die Klinische Medizin" * Sommerfest für Praxen des PRoMPT-Forschungsprojektes

kurz und kn@pp news : Nr. 8 (2007)

* Vorankündigung: 1. Frankfurter Tag der Allgemeinmedizin * Tipps zur Fehlervermeidung * STERN-Titel zu Bluthochdruck unter Mitarbeit des Instituts * 2. Teil DEGAM-Leitlinie "Herzinsuffizienz", Langfassung * Start des anonymen Fehlerzirkels! * Über 1000 Studierende in Evidenzbasierter Medizin ausgebildet * Wissenschaftliche/r Mitarbeiter/in gesucht

Speech perception in noise in CI systems with different microphones (2007)

Juliane Wechtenbruch Uwe Baumann Tobias Rader John Martin Hempel

Causes of metabolic acidosis in canine hemorrhagic shock: role of unmeasured ions (2007)

Dirk Steffen Brügger Gregor I. Kemming Matthias Jacob Franz Georg Meisner Christoph J. Wojtczyk Kristian Packert Peter E. Keipert N Simon Faithfull Oliver Habler Bernhard F. Becker Markus Rehm

INTRODUCTION: Metabolic acidosis during hemorrhagic shock is common and conventionally considered to be due to hyperlactatemia. There is increasing awareness, however, that other nonlactate, unmeasured anions contribute to this type of acidosis. METHODS: Eleven anesthetized dogs were hemorrhaged to a mean arterial pressure of 45 mm Hg and were kept at this level until a metabolic oxygen debt of 120 mLO2/kg body weight had evolved. Blood pH, partial pressure of carbon dioxide, and concentrations of sodium, potassium, magnesium, calcium, chloride, lactate, albumin, and phosphate were measured at baseline, in shock, and during 3 hours post-therapy. Strong ion difference and the amount of weak plasma acid were calculated. To detect the presence of unmeasured anions, anion gap and strong ion gap were determined. Capillary electrophoresis was used to identify potential contributors to unmeasured anions. RESULTS: During induction of shock, pH decreased significantly from 7.41 to 7.19. The transient increase in lactate concentration from 1.5 to 5.5 mEq/L during shock was not sufficient to explain the transient increases in anion gap (+11.0 mEq/L) and strong ion gap (+7.1 mEq/L), suggesting that substantial amounts of unmeasured anions must have been generated. Capillary electrophoresis revealed increases in serum concentration of acetate (2.2 mEq/L), citrate (2.2 mEq/L), alpha-ketoglutarate (35.3 microEq/L), fumarate (6.2 microEq/L), sulfate (0.1 mEq/L), and urate (55.9 microEq/L) after shock induction. CONCLUSION: Large amounts of unmeasured anions were generated after hemorrhage in this highly standardized model of hemorrhagic shock. Capillary electrophoresis suggested that the hitherto unmeasured anions citrate and acetate, but not sulfate, contributed significantly to the changes in strong ion gap associated with induction of shock.

Reference values and physiological characterization of a specific isolated pig kidney perfusion model (2007)

Volker Unger Christian Grosse-Siestrup Claudia Fehrenberg Axel Fischer Michael Meissler Jan David Alexander Groneberg

BACKGROUND: Models of isolated and perfused kidneys are used to study the effects of drugs, hazardous or toxic substances on renal functions. Since physiological and morphological parameters of small laboratory animal kidneys are difficult to compare to human renal parameters, porcine kidney perfusion models have been developed to simulate closer conditions to the human situation, but exact values of renal parameters for different collection and perfusion conditions have not been reported so far. If the organs could be used out of regular slaughtering processes animal experiments may be avoided. METHODS: To assess renal perfusion quality, we analyzed different perfusion settings in a standardized model of porcine kidney hemoperfusion with organs collected in the operating theatre (OP: groups A-D) or in a public abattoir (SLA: group E) and compared the data to in vivo measurements in living animals (CON). Experimental groups had defined preservation periods (0, 2 and 24 hrs), one with additional albumin in the perfusate (C) for edema reduction. RESULTS: Varying perfusion settings resulted in different functional values (mean +/- SD): blood flow (RBF [ml/min*100 g]: (A) 339.9 +/- 61.1; (C) 244.5 +/- 53.5; (D) 92.8 +/- 25.8; (E) 153.8 +/- 41.5); glomerular filtration (GFR [ml/min*100 g]: (CON) 76.1 +/- 6.2; (A) 59.2 +/- 13.9; (C) 25.0 +/- 10.6; (D) 1.6 +/- 1.3; (E) 16.3 +/- 8.2); fractional sodium reabsorption (RFNa [%] (CON) 99.8 +/- 0.1; (A) 82.3 +/- 8.1; (C) 86.8 +/- 10.3; (D) 38.4 +/- 24.5; (E) 88.7 +/- 5.8). Additionally the tubular coupling-ratio of Na-reabsorption/O2-consumption was determined (TNa/O2-cons [mmol-Na/mmol- O2] (CON) 30.1; (A) 42.0, (C) 80.6; (D) 17.4; (E) 23.8), exhibiting OP and SLA organs with comparable results. CONCLUSION: In the present study functional values for isolated kidneys with different perfusion settings were determined to assess organ perfusion quality. It can be summarized that the hemoperfused porcine kidney can serve as a biological model with acceptable approximation to in vivo renal physiology, also if the organs originate from usual slaughtering processes.

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