Zusammenfassung Nach intravenoser Verabreichung von β-Pyridylcarbinol, dem Alkohol der Nikotinsaure, kommt es beim Miniaturschwein zu einem Hamatokritanstieg um 28 % innerhalb von 10 Minuten und zu einem mittleren Anstieg des Plasmainsulins um 129% innerhalb von 20 Minuten. Die freien Fettsauren und das Plasmakalium zeigen ein gleichartiges Verhalten wie beim Menschen. Bezuglich des Ausmases und der Dauer des Abfalles und der Starke des Reboundphaenomens der freien Fettsauren konnte eine Dosis-wirkungsbeziehung wahrscheinlich gemacht werden. Summary Effect on plasma glucose, insulin, potassium, free fatty acids and haematocrit of β-pyridylcarbinol in miniature pigs Following the intravenous injection of β-pyridylcarbinol, the alcohol of nicotinic acid, to minipigs the haematocrit shows an average increase of 28 % within 10 minutes. Plasma insulin shows an increase of 129% within 20 minutes. Plasma potassium and free fatty acids change in a similar way as in man. Concerning the magnitude and duration of the decrease and the following rebound of the free fatty acids a dose response relation seems to exist. Resume Influence du β-Pyridylcarbinol sur le glucose du plasma, l'insuline, le potassium, les acides gras libres et l'hematocrite chez le porc miniature Apres application intraveineuse de β-Pyridylcarbinol (alcool de l'acide nicotinique), on observe chez le porc miniature une elevation de l'heatocrite de 28 % en l'espace de 10 minutes et une augmentation moyenne de l'insuline plasmatique de 129 % dans l'espace de 20 minutes. Les acides gras libres et le potassium du plasma ont un comportement egal a celui constate chez l'etre humain. En considerant la mesure, la duree et l'intensite du phenomene de brusque retour des acides gras libres, il serait vraissemblablement possible de faire un rapport dose-effet. Resumen El influjo de β-piridilcarbinol sobre la glucosa plasmatica, insulina, potasio, acidos grasos libres y hematocrito en el cerdo miniatura Tras la administracion intravenosa de β-piridilcarbinol, el alcohol del acido nicotinico, se registra en el cerdo miniatura un aumento del hematocrito en un 28 % en un plazo de 10 minutos y un aumento medio de la insulina plasmatica en un 129 % a lo largo de 20 minutos. Los acidos grasos libres y el potasio plasmatico muestran el mismo comportamiento que en las personas. Con respecto a la magnitud y la duracion de la disminucion y de la intensidad del fenomeno de rebote de los acidos grasos libres, parece existir cierta relacion dosis-respuesta.

Zusammenfassung Um Grundlagendaten über Beziehungen zwischen Nahrungsaufnahme und Kohlenhydratstoffwechsel am Miniaturschwein zu erhalten, wurden die zirkadianen Plasmaglucose- und Insulinspiegel bestimmt. Im Gegensatz zu Befunden am Menschen war der maximale Plasmainsulinanstieg nach der Morgenfütterung gleich rasch und gleich hoch wie nach der Nachmittagsfütterung, dagegen fand sich auch beim Schwein ein stark verzögerter Abfall des Plasmainsulins nach der zweiten Fütterung. Nachts blieb der Insulinspiegel konstant, während der Glucosespiegel deutlich abfiel. Der Quotient Insulin/Glucose war nach der zweiten Fütterung — abgesehen von der unmittelbar postprandialen Periode — größer als nach der Morgenfütterung. Für die Assistenz bei den operativen Eingriffen möchten wir Frl. G. Bolz an dieser Stelle danken. Summary Circadian variations in plasma glucose and insulin in young miniature pigs In order to establish basic data for the relationships between food intake and carbohydrate metabolism in miniature pigs the variations during the day of plasma glucose and insulin were determined. In contrast to the finding in man, the maximal plasma insulin rise after the morning feed was as rapid and as high as after the afternoon feed, whereas the pig showed, as does man, a markedly slowed fall in plasma insulin after the second feed. During the night the insulin level remained constant, whereas the glucose level fell appreciably. The quotient insulin/glucose was higher, save for the immediate post-prandial period, after the second feed than after the morning feed. Résumé Variations du glucose et de l'insuline plasmatiques dans le courant de la journée chez le porc miniature Pour obtenir des valeurs de base sur les relations entre l'ingestion d'aliments et le métabolisme des hydrates de carbone chez le porc miniature, on a déterminé les taux de glucose et d'insuline plasmatiques dans le courant de la journée. A l'encontre des résultats trouvés chez l'homme, l'augmentation maximum d'insuline plasmatique, après le repas matinal, est aussi rapide et aussi élevée qu'après le repas de l'après-midi; par contre, on observe chez l'homme comme chez le porc, un important retard dans la diminution de l'insuline plasmatique après le deuxième repas. Pendant la nuit, le taux d'insuline reste constant, alors que le taux du glucose diminue nettement. Le quotient insuline/glucose est plus élevé après le deuxième repas qu'après le premier, à l'exception de la période post-prandiale immédiate. Resumen Oscilaciones circadianas de la glucosa e insulina plasmáticas en el cerdo miniatura joven Para obtener datos fundamentales sobre las relaciones entre la ingestión de alimentos y el metabolismo hidrocarbonado en el cerdo miniatura, se valoraron los niveles circadianos de glucosa e insulina plasmáticas. En contraposición a los hallazgos en el hombre, el aumento máximo de insulina plasmática se instauraba rápidamente después de la alimentación matutina y con la misma intensidad que después de la alimentación vespertina, pero en cambio también en el cerdo se halló un descenso muy diferido de la insulina plasmática después de la segunda alimentación. Por la noche permanecía constante el nivel insulínico, mientras que descendía de forma manifiesta el nivel glucémico. El cociente insulina/glucosa era mayor después de la alimentación segunda — prescindiendo del periodo postprandial inmediato — que a continuación de la alimentación matutina.

Conference Article| December 01 1988 Biochemical studies of glucosidase encapsulated in erythrocytes ULRICH SPRANDEL; ULRICH SPRANDEL 1Polyclinic, University of Munich, Pettenkoferstr. 8a, 8000 Munich 2, F.R.G. Search for other works by this author on: This Site PubMed Google Scholar NEPOMUK ZÖLLNER NEPOMUK ZÖLLNER 1Polyclinic, University of Munich, Pettenkoferstr. 8a, 8000 Munich 2, F.R.G. Search for other works by this author on: This Site PubMed Google Scholar Author and article information Publisher: Portland Press Ltd Received: June 20 1988 Online ISSN: 1470-8752 Print ISSN: 0300-5127 © 1988 Biochemical Society1988 Biochem Soc Trans (1988) 16 (6): 1051–1052. https://doi.org/10.1042/bst0161051 Article history Received: June 20 1988 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation ULRICH SPRANDEL, NEPOMUK ZÖLLNER; Biochemical studies of glucosidase encapsulated in erythrocytes. Biochem Soc Trans 1 December 1988; 16 (6): 1051–1052. doi: https://doi.org/10.1042/bst0161051 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 1988 Biochemical Society1988 Article PDF first page preview Close Modal You do not currently have access to this content.

Erythrocytes have been proposed as cellular carriers for enzymes and drugs for protected delivery, slow release, or targeting to specific organs. Several studies have established the heterogeneity of resealed carrier erythrocytes concerning various characteristics, including morphology. Carrier erythrocytes were prepared by hypo-osmotic dialysis and consecutive iso-osmotic resealing at different temperatures, and the morphology of these cells was studied by scanning electron microscopy. Different cell shapes could be prepared by temperature variations during resealing or incubation. All intermediate shapes of echinocytosis were observed at low temperatures or with depleted energy supply but could be reversed to biconcave discocytes. Resealing at 4°C resulted in highest percentage of echinocytes III, spherocytes, and leaky cells. Spontaneous resealing of 20% of the cells was obtained at high lysis temperatures. Combining low temperatures for lysis and high temperatures for resealing and sufficient energy supply are advantageous for highest recovery of biconcave discocytes. Shape of the erythrocyte, is the result of divergent forces, and temperature during resealing was found to be an important factor.

Publisher Summary This chapter describes the magnetically responsive erythrocytes ghosts. The studies described were to examine whether ferromagnetic micromolecules, so-called ferrofluids, can be entrapped in erythrocyte ghosts, and if such ferromagnetic ghosts can be influenced by magnetic fields in vitro . This would open the door to in vivo studies on drug targeting by magnetically responsive erythrocyte ghosts. These studies have shown that it is possible to entrap magnetite particles in erythrocyte ghosts. The substance presently available, however, has a certain cytotoxic and hemolytic activity. Other kinds of ferrofluids should be produced, avoiding any additive of potential membrane-damaging detergents, or a coating (e.g., protein) could be applied around the magnetite particles to reduce their toxicity. If these problems could be solved, it would be possible to prevent such high leak streams as observed in the current studies. Then, magnetically responsive erythrocyte ghosts might become useful for drug targeting.

Erythrocytes have been proposed as cellular carriers for enzyme replacement therapy. Urate oxidase was encapsulated in erythrocytes using different methods. Average encapsulation was found to be 7 % of the added enzyme activity using a dialysis technique and 1.75 % using a direct hemolysis procedure. Binding of enzyme to the membrane could be excluded. Optimum enzyme activity of urate oxidase encapsulated in erythrocytes was found to be at pH 9.5 and 42° C. Suspension of urate oxidase loaded erythrocytes in uric acid containing medium was followed by an initial decrease of uric acid which could be related to the available space inside the cells. After 40 minutes steady-state levels were reached and the further decrease of uric acid showed a direct relation to the added amount of entrapped enzyme. Within 24 hours there was a loss of 8 %, within 7 days of 15 % of the enzyme activity, which could be related to hemolysis. This system was not studied in vivo, since it was not possible to elevate uric acid in a laboratory animal. However, these experiments demonstrate, that it would be possible to decrease elevated uric acid levels by urate oxidase loaded erythrocytes in human.

Erythrocytes have been proposed as biogradable cellular carriers for drugs. Potentials of this therapeutic approach are organ-specific targeting, protection and prolonged in vivo function of the encapsulated drugs. Previous studies demonstrated the advantage of a hypo-osmotic dialysis procedure for macromolecule loading resulting in cells that are closely similar to normal erythrocytes. Osmotic fragility of unloaded and loaded "carrier" erythrocytes was studied both in respect of shelf-life and in vivo survival. Sudden haemolysis which is characteristic for normal erythrocytes was never obtained with carrier erythrocytes. Haemolysis appeared at all osmotic pressures and increased stepwise indicating the existence of various cell populations. However, the majority of cells were haemolysed at lower values of the osmotic fragility curve. Osmotic fragility was highly increased when cytotoxic chemotherapeutics were encapsulated, and these cells appeared as spherocytes using scanning electron microscopy. Osmotic fragility proved to be a simple but reliable method for the in vitro evaluation of carrier erythrocytes and the effect of the encapsulated substances.

Die Auswahl therapeutisch wirksamer Verfahren zur Behandlung der Ösophagusvarizenblutung bleibt weiterhin eine schwierige ärztliche Entscheidung. Die endoskopische Ösophagusvarizensklerosierung [4, 12, 15] und die Notfallshuntoperation sind mit einer erheblichen Komplikationsrate bzw. unerwünschten Spätfolgen belastet [4, 12, 16]. Daher hatte die medikamentöse Behandlung mit β-Rezeptorenblockern als Prophylaxe rezidivierender Ösophagusvarizenblutungen seit den hoffnungsvollen Berichten von Lebrec [6–10] zunächst erhebliche Bedeutung erlangt. In den letzten Monaten wurde jedoch die therapeutische Wertigkeit des Vorgehens zunehmend Gegenstand kontroverser Diskussionen [3, 6], da prospektive klinische Studien die Wirksamkeit von β-Rezeptorenblockern als Prophylaxe einer Ösophagusvarizenblutung zunehmend einschränken oder überhaupt keinen Effekt fanden.

Conference Abstract| March 01 1981 Characteristics in vitro and Survival in vivo of Erythrocyte ‘Ghosts’ Prepared Under Iso-Osmotic Conditions by Using High Voltage Electric Fields R. A. Chalmers; R. A. Chalmers 1Division of Inherited Metabolic Diseases, MRC Clinical Research Centre, Harrow, HA1 3UJ, Middlesex, U.K. Search for other works by this author on: This Site PubMed Google Scholar U. Sprandel; U. Sprandel 1Division of Inherited Metabolic Diseases, MRC Clinical Research Centre, Harrow, HA1 3UJ, Middlesex, U.K. Search for other works by this author on: This Site PubMed Google Scholar A. R. Hubbard A. R. Hubbard 1Division of Inherited Metabolic Diseases, MRC Clinical Research Centre, Harrow, HA1 3UJ, Middlesex, U.K. Search for other works by this author on: This Site PubMed Google Scholar Clin Sci (Lond) (1981) 60 (3): 2P–3P. https://doi.org/10.1042/cs060002Pc Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation R. A. Chalmers, U. Sprandel, A. R. Hubbard; Characteristics in vitro and Survival in vivo of Erythrocyte ‘Ghosts’ Prepared Under Iso-Osmotic Conditions by Using High Voltage Electric Fields. Clin Sci (Lond) 1 March 1981; 60 (3): 2P–3P. doi: https://doi.org/10.1042/cs060002Pc Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu nav search search input Search input auto suggest search filter All ContentAll JournalsClinical Science Search Advanced Search This content is only available as a PDF. Article PDF first page preview Close Modal You do not currently have access to this content.

Recent work leading to the production of resealed erythrocytes with enhanced in vivo survival is reviewed. The term ‘carrier erythrocytes’ is proposed for these cells and possible therapeutic uses are discussed.

An Präparaten, die eine eindeutige Indikation besitzen und der Dauerbehandlung dienen, lassen sich einige Unterschiede zwischen den Verordnungen vor der Krankenhausaufnahme und während des stationären Aufenthaltes darstellen. Es handelt sich um die Antidiabetika Insulin, Glibenclamid und Tolbutamid, die Antisympathotonika Methyldopa und Clonidin, den β-Blocker Propranolol und den Kalziumantagonisten Verapamil. Es wurde ermittelt, welche Patienten diese Präparate vor der Klinikaufnahme angewendet hatten, und außerdem verfolgt, bei welchem Patienten das Präparat in der Klinik beibehalten und auch danach zur Weiterbehandlung empfohlen wurde, und bei welchen Patienten und aus welchen Gründen das Präparat in der Klinik abgesetzt worden war.

Resealed erythrocyte ‘ghosts’ have been proposed as in vivo carriers for enzymes in the therapy of inherited metabolic diseases. A long life-span of this carrier is required when the erythrocyte ‘ghost’ is intended to be the site of substrate degradation in the circulation. Erythrocyte ‘ghosts’ have been prepared that show cell content and membrane transport characteristics that are closely similar to those of normal erythrocytes. Since the morphology of these ‘ghosts’ could probably also affect the in vivo life-span, haemoglobin-containing human erythrocyte ‘ghosts’ have been studied using scanning electron-microscopy.

The transport of organic acids across the membrane of resealed haemoglobin-containing erythrocyte 'ghosts' prepared by a dialysis technique has been studied. The present work forms part of studies directed towards the use of erythrocyte cellular carriers in enzyme-replacement therapy of inherited metabolic diseases. Oxalic acid, glycollic acid and glyoxylic acid were taken as representative of aliphatic acids of low molecular mass and benzoic and cinnamic acids as representative of unsubstituted aromatic acids. These selected acids are important in the diseases with which the present work is concerned. Comparison of influx and efflux transport characteristics showed that erythrocyte 'ghosts' retain transport properties closely similar to those of normal erythrocytes. Rapid transport was observed with all organic acids studied and there was a linear relationship between initial amount of influx and external concentration of aliphatic acid. Saturation of the transport system was not observed up to 1 mM external concentration, and the presence of plasma in the external medium had no effect on transport characteristics. Transport in intact erythrocytes and prepared erythrocyte 'ghosts' from patients with hyperoxaluria was also studied.