Linking immunity to atherosclerosis: implications for vascular pharmacology--a tribute to Göran K. Hansson

For the past decade, we have deepened our understanding of the pathogenesis of atherosclerosis, a chronic arterial disease that causes cardiac and cerebral infarction and peripheral vascular disorders. Because of this extended understanding, more effective strategies for prevention and treatment of this disease are emerging. One of the fundamental mechanisms that lead to progress or regression in atherosclerosis, thus influencing its life-threatening complications, occurs through functional changes in vascular immunity and inflammation. This review briefly summarizes the discoveries in basic and translational sciences in this area and recent advances in clinical medicine against atherosclerotic vascular diseases.     

Festschrift Professor Jürgen C. Frölich

European Journal of Clinical Pharmacology -     

Inhalation studies with the Göttingen minipig

A method for inhalative exposure of minipigs to aerosols and gases has been developed. Minipigs are exposed via mask inhalation to the test substance using a computer-controlled exposure system that permits simultaneous exposure of groups of four animals in parallel to different controlled dose levels. We studied inhalation treatment of verapamil, a cardiovascular drug, and show good absorption and favorable pharmacokinetics when compared with iv drug application. The results shown in this study encourage inhalation studies with the G?ttingen minipig.     

Inhalation Studies with the Göttingen Minipig

A method for inhalative exposure of minipigs to aerosols and gases has been developed. Minipigs are exposed via mask inhalation to the test substance using a computer-controlled exposure system that permits simultaneous exposure of groups of four animals in parallel to different controlled dose levels. We studied inhalation treatment of verapamil, a cardiovascular drug, and show good absorption and favorable pharmacokinetics when compared with iv drug application. The results shown in this study encourage inhalation studies with the Göttingen minipig.     

Cell adhesion molecules as therapeutic targets: interview with Professor Michael P Schön

Professor Michael P Schön (University of Würzburg) was interviewed by Emma Quigley (Commissioning Editor, Expert Opinion) on 17^th October 2006.

Professor Michael P Schön currently holds the position of Professor of Dermatology and Experimental Biomedicine at the University of Würzburg. He received his MD degree in 1992 from the University of Ulm in Germany. His internationally successful scientific career has led him to study dermatology and immunology at the University of Berlin, Harvard Medical School, the University of Düsseldorf and the University of Magdeburg. With various research awards and certificates in dermatology, immunology and dermatopathology, Professor Schön has published > 100 papers. He has also been a guest editor and on the Editorial Board of various publications.     

Gö 6983 exerts cardioprotective effects in myocardial ischemia/reperfusion

Ischemia followed by reperfusion (I/R) in the presence of polymorphonuclear leukocytes (PMNs) results in cardiac contractile dysfunction. Inhibiting protein kinase C (PKC) inhibits the release of superoxide from PMNs. The compound G? 6983 is an inhibitor of all five PKC isoforms present in PMNs. Therefore, we hypothesized that G? 6983 could attenuate PMN-induced cardiac dysfunction by suppression of superoxide production from PMNs. We studied isolated rat hearts following ischemia (20 minutes) and reperfusion (45 minutes) infused with activated PMNs. In hearts reperfused with PMNs and G? 6983 (100 nM, n = 7), left ventricular developed pressure (LVDP) and the rate of LVDP (+dP/dt max) recovered to 89 +/- 7% and 74 +/- 2% of baseline values, respectively, at 45 minutes postreperfusion compared with I/R hearts (n = 9) receiving PMNs alone, which only recovered to 55 +/- 3% and 45 +/- 5% of baseline values for LVDP and +dP/dtmax, respectively (P < 0.01). G? 6983 (100 nM) significantly reduced PMN adherence to the endothelium and infiltration into the myocardium compared with I/R + PMN hearts (P < 0.01), and significantly inhibited superoxide release from PMNs by 90 +/- 2% (P < 0.01). In the presence of PMNs, G? 6983 attenuated post-I/R cardiac contractile dysfunction, which may be related in part to decreased superoxide production.     

The incidence of congenital malformations and variations in Göttingen minipigs

Knowledge of the incidence of spontaneous congenital abnormalities is critical for the accurate interpretation of findings in teratogenicity studies in any species. In this paper, results of the examination of 1739 neonatal Göttingen Minipigs are presented. Over the 2-year period under consideration, the incidence of external and visceral malformations was less than 0.2 and 0.1%, respectively. The most common external malformations were syndactyly, limb hyperflexion, domed head and scoliosis. The most common internal malformations were undescended testes, ventricular septal defect, diaphragmatic hernia and atrial septal defects. Pentadactyly and variation in the aortic arch’s bifurcation (absent truncus bicaroticus) were the most common variations. These data will help support the use of the Göttingen Minipig as a non-rodent species in embryofetal development studies where concerns persist about the availability of background data.     

Cell adhesion molecules as therapeutic targets: interview with Professor Michael P Schön. Interviewed by Emma Quigley

Professor Michael P Sch?n (University of Würzburg) was interviewed by Emma Quigley (Commissioning Editor, Expert Opinion) on 17th October 2006. Professor Michael P Sch?n currently holds the position of Professor of Dermatology and Experimental Biomedicine at the University of Würzburg. He received his MD degree in 1992 from the University of Ulm in Germany. His internationally successful scientific career has led him to study dermatology and immunology at the University of Berlin, Harvard Medical School, the University of Düsseldorf and the University of Magdeburg. With various research awards and certificates in dermatology, immunology and dermatopathology, Professor Sch?n has published > 100 papers. He has also been a guest editor and on the Editorial Board of various publications.     

Analyzing Receiver Operating Characteristic Curves with SAS,by M. Gönen

In infectious diseases, it is important to predict the long-term persistence of vaccine-induced antibodies and to estimate the time points where the individual titers are below the threshold value for protection. This article focuses on HPV-16/18, and uses a so-called fractional-polynomial model to this effect, derived in a data-driven fashion. Initially, model selection was done from among the second- and first-order fractional polynomials on the one hand and from the linear mixed model on the other. According to a functional selection procedure, the first-order fractional polynomial was selected. Apart from the fractional polynomial model, we also fitted a power-law model, which is a special case of the fractional polynomial model. Both models were compared using Akaike's information criterion. Over the observation period, the fractional polynomials fitted the data better than the power-law model; this, of course, does not imply that it fits best over the long run, and hence, caution ought to be used when prediction is of interest. Therefore, we point out that the persistence of the anti-HPV responses induced by these vaccines can only be ascertained empirically by long-term follow-up analysis.     

Electroretinographic and Ophthalmologic Examinations in the Yucatan Micropig and in the Göttingen Minipig

Abstract

External gross observations of the eye and its adnexae, ocular reflexes, anterior ocular segment biomicroscopic examinations, fundic examinations performed with an indirect ophthalmoscope, and/or electroretinographic investigations (ERG) were carried out on 112 7-12-month-old Yucatan micropigs, on 18 6-8-week-old, and 81 2-10-month old Gottingen minipigs to evaluate the incidence of observed ocular abnormalities and to compare the ERG waves. A statistical comparison was performed for these findings.

The most important ocular defects were classified as remnants of embryological vascular tissue. The other findings were considered either as embryonic remnants or of nondeterminate etiology. The most noteworthy findings were, in decreasing order of incidence, for Yucatan micropigs, 6-8 week-old and 2-10-monfh-old Gottingen minipigs, respectively, hyaloid artery remnants (82.1%, 83.3%, and 46.3%), pupillary     

Mittheilungen aus dem pharmakologischen Experimentalcursus von Prof. Th. Husemann in Göttingen

Ohne Zusammenfassung     

In-vivo evaluation of prolonged release bilayer tablets of anti-Parkinson drugs in Göttingen minipigs

Objectives Patients with Parkinson's disease can benefit from controlled released levodopa dosage forms since there is a clear clinical advantage in obtaining sustained plasma concentrations. The purpose of this study was to obtain a tablet that prolonged the release of levodopa. Methods A novel bilayer tablet, consisting of an immediate release layer containing nebicapone (100 mg) and an erosion‐matrix type prolonged release layer containing levodopa (100 mg) and carbidopa (25 mg) was developed (LCN PR). A pharmacokinetic study in Göttingen minipigs was performed to evaluate this formulation. Key findings LCN PR tablets prolonged the in‐vitro release of levodopa in HCl 0.1 m for more than 3 h. In‐vivo plasma levodopa levels peaked at a later time point with LCN PR tablets as compared with that obtained with Sinemet 100/25 (2.7 vs 0.5 h). Nebicapone increased the maximum plasma concentration and area under the plasma concentration–time curve values for levodopa. Conclusions The results obtained suggested that LCN PR tablets may have decreased the number of tablets and daily intake in the treatment of patients with Parkinson's disease.     

Professor Margareta Hammarlund-Udenaes – a Modern and Visionary Mentor

Pharmaceutical Research -