bluuebunny/crossref_metadata_2025_split huggingface dataset:
Semaglutid – ein neuer langwirksamer GLP-1-Rezeptor-Agonist mit nachgewiesener kardiovaskulärer Ereignisreduktion bei Typ-2-Diabetes
Authors: Seufert Jochen , Nauck Michael A. , Gallwitz Baptist 
Published: July 2018

ZUSAMMENFASSUNGZur Therapie von Menschen mit Typ-2-Diabetes wurde mit Semaglutid ein neuer, lang wirksamer Glucagon-like-peptide1-Rezeptor-Agonist (GLP-1-RA) für die einmal wöchentliche Gabe entwickelt. Das weltweite Phase-3-Studienprogramm umfasste mehr als 7000 Patienten, die in eine der randomisierten, kontrollierten Studien SUSTAIN 1 bis 6 eingeschlossen wurden. In SUSTAIN 1 bis 5 zeigten sich nach 30 bzw. 56 Wochen mittlere HbA1c-Reduktionen zwischen 1,2 und 1,45 % (Semaglutid 0,5 mg) bzw. 1,5 und 1,8 % (Semaglutid 1,0 mg) mit signifikanten Vorteilen gegenüber Placebo, Sitagliptin 1 × täglich 100 mg, Exenatid-Depot-Injektionssuspension (nur 1,0 mg Semaglutid untersucht) und Insulin glargin 100 E/ml (Startdosis 10 E 1 × täglich). Das Körpergewicht verringerte sich unter Semaglutid im Mittel um 3,5 bis 4,3 kg (0,5 mg) und 4,5 bis 6,4 kg (1,0 mg). Die kardiovaskuläre Outcome-Studie SUSTAIN 6 ergab nach 2-jähriger Behandlung mit Semaglutid 0,5 mg oder 1,0 mg im Vergleich zu Placebo – jeweils im Rahmen des „Standard of Care“ – eine relative Risikoreduktion hinsichtlich des primären kombinierten kardiovaskulären Endpunkts um 26 % von absolut 8,9 % auf 6,6 % (p = 0,02 für die Überlegenheit). Außerdem zeigten sich unter Semaglutid im Vergleich zur Placebogruppe weniger Nephropathie-Ereignisse (3,8 % vs. 6,1 %; p = 0,005), aber mehr Retinopathie-Komplikationen (3,0 % vs. 1,8 %; p = 0,02), um 0,66 %-Punkte (0,5 mg) und 1,05 %-Punkte (1,0 mg) stärkere HbA1c-Reduktionen nach 104 Wochen (jeweils p < 0,0001) und um 2,9 kg (0,5 mg) und 4,4 kg (1,0 mg) stärkere Gewichtsreduktionen (jeweils p < 0,0001). Wie bei anderen GLP-1-RA finden sich unter Semaglutid Reduktionen des systolischen Blutdrucks, Anstiege der Herzfrequenz, vermehrt gastrointestinale Nebenwirkungen und ein in Anbetracht der deutlichen HbA1c-Reduktion relativ geringes Hypoglykämierisiko. Zusammenfassend liegen die Stärken von Semaglutid in einer ausgeprägt effektiven HbA1c-Reduktion, der deutlichen Gewichtsreduktion und vorteilhaften kardiovaskulären Endpunktdaten.
Herzinsuffizienz und Diabetes
Authors: Rau Matthias , Lehrke Michael 
Published: July 2018

ZUSAMMENFASSUNGEpidemiologische und klinische Daten weisen auf eine hohe Prävalenz und Inzidenz einer Herzinsuffizienz bei Patienten mit Diabetes mellitus hin, was mit einer schlechten Prognose assoziiert ist.Die vorliegende Übersicht fasst die therapeutischen Strategien zur Behandlung einer Herzinsuffizienz bei Patienten mit Diabetes zusammen. Des Weiteren wird die Behandlung des Diabetes bei Patienten mit Herzinsuffizienz unter Berücksichtigung der aktuellen klinischen Studien diskutiert.
Typ-2-Diabetes – Kriterien für die Wahl des Antidiabetikums
Authors: Gallwitz Baptist 
Published: July 2018

ZUSAMMENFASSUNGDie moderne Behandlung des Typ-2-Diabetes verfolgt einen patientenzentrierten Ansatz. Die Festlegung des HbA1c-Zielwerts erfolgt unter Berücksichtigung der individuellen Situation der Betroffenen wie Alter, Krankheitsdauer und Komorbiditäten. Dem Behandler stehen in der stufenweisen Therapie des Typ-2-Diabetes mittlerweile mehrere Optionen mit unterschiedlichen Wirkmechanismen zur Verfügung, die gemäß der nationalen Versorgungsleitlinie nach Lebensstilintervention und Metformin-Basistherapie zum Einsatz kommen können. Studienergebnisse zeigen Unterschiede zwischen den einzelnen Substanzklassen hinsichtlich antihyperglykämischer Wirksamkeit, Hypoglykämierisiko und Effekt auf das Körpergewicht. Auch die Wirkung auf kardiovaskuläre Parameter tritt zunehmend in den Fokus der Arzneimittelwahl. Diese Abwägung von Wirksamkeit und Sicherheit spiegelt sich in der immer gebräuchlicheren Darstellung des kombinierten Endpunktes „Erreichen des Ziel-HbA1c ohne Hypoglykämien und ohne Gewichtszunahme“ in Studien wider. Eine leitliniengerechte, evidenzbasierte Einordnung der zur Verfügung stehenden Therapieoptionen soll der Orientierung im Praxisalltag dienen.
Transorale videoendoskopische Resektion von Kopf-Hals-Tumoren in 4-Hand-Technik
Authors: Engel Stephan , Taxeidis Margaritis , Reichel Oliver 
Published: July 2018

Zusammenfassung
Einleitung Videoendoskopische Operationsverfahren in 4-Hand-Technik sind bereits in der Visceralchirurgie bei laparoskopischen Eingriffen sowie bei der
Hypophysenchirurgie etabliert. Auch in der Tumorchirurgie im Kopf-Hals-Bereich gewinnt die transorale videoendoskopische Resektion von Tumoren in 4-Hand-Technik
(TOVR) zunehmend an Bedeutung.
Material und Methoden Seit März 2013 wurden erfolgreich 28 transorale videoendoskopische Tumorresektionen von Oropharynx (n = 5) –, Hypopharynx (n = 12) –
und Larynxkarzinomen (n = 11) in 4-Hand-Technik durchgeführt.
Ergebnisse In allen 28 Fällen wurde transoral eine R0-Resektion ohne Erweiterung des Eingriffs durch einen Zugang von transcervikal erreicht. Auch bei
Patienten mit schlechter Beweglichkeit im HWS-Bereich (n = 9) gelang durch den Einsatz von Winkeloptiken über ein Kleinsasser- oder Weerda-Rohr per TOVR eine
transorale R0-Tumorresektion.
Schlußfolgerungen Die TOVR ist ein effektives, preisgünstiges und minimalinvasives Operationsverfahren bei Tumoren im Kopf-Hals-Bereich mit zahlreichen
Vorteilen im Vergleich zur CO2-Laserresektion und stellt eine echte Alternative zu den herkömmlichen Resektionsverfahren dar.
Recent Advances in Total Synthesis via Metathesis Reactions
Authors: Sarabia Francisco , Cheng-Sánchez Iván 
Published: July 2018

The metathesis reactions, in their various versions, have become a powerful and extremely valuable tool for the formation of carbon–carbon bonds in organic synthesis. The plethora of available catalysts to perform these reactions, combined with the various transformations that can be accomplished, have positioned the metathesis processes as one of the most important reactions of this century. In this review, we highlight the most relevant synthetic contributions published between 2012 and early 2018 in the field of total synthesis, reflecting the state of the art of this chemistry and demonstrating the significant synthetic potential of these methodologies.1	Introduction2	Alkene Metathesis in Total Synthesis2.1	Total Synthesis Based on a Ring-Closing-Metathesis Reaction2.2	Total Synthesis Based on a Cross-Metathesis Reaction2.3	Strategies for Selective and Efficient Metathesis Reactions of Alkenes2.3.1	Temporary Tethered Ring-Closing Metathesis2.3.2	Relay Ring-Closing Metathesis2.3.3	Stereoselective Alkene Metathesis2.3.4	Alkene Metathesis in Tandem Reactions3	Enyne Metathesis in Total Synthesis3.1	Total Syntheses Based on a Ring-Closing Enyne-Metathesis Reaction3.2	Total Syntheses Based on an Enyne Cross-Metathesis Reaction3.3	Enyne Metathesis in Tandem Reactions4	Alkyne Metathesis in Total Synthesis4.1	Total Synthesis Based on a Ring-Closing Alkyne-Metathesis Reaction4.2	Other Types of Alkyne-Metathesis Reactions5	Conclusions
High Resolution Electrophoretic Analysis of Human Fibrinogen and Its Crosslinked Intermediates
Authors: Carrell N A , Holahan J R , White G C , McDonagh J 
Published: July 2018

SummaryHeterogeneity in human fibrinogen was examined using an improved two-dimensional isoelectric focusing-SDS polyacrylamide gel electrophoretic procedure. Four different preparations of fibrinogen were compared: single donor fibrinogen prepared from plasma by precipitation with ammonium sulfate or by affinity chromatography on fibrin-monomer Sepharose, fraction I—4 prepared from Cohn fraction I paste, and Kabi grade L. The subunit Aα, Bβ, and γ chains in all preparations had marked charge heterogeneity. The three chains were clearly separated from each other and a range of isoelectric points for each chain could be assigned. Minor variations in the subunit heterogeneity of the different preparations were found. Intermediates in the transition from fibrinogen to crosslinked fibrin were also examined. A striking increase in the heterogeneity of the α chain was observed during crosslinking.
Failure of Salicylate to Reduce Inhibition of Human Venous Prostacyclin in Synthesis by Conventional Dose Aspirin
Authors: Hanley S P , Hughes J 
Published: July 2018

SummaryEx vivo venous prostacyclin synthesis was measured in 24 patients who received no medication, or a single oral dose of aspirin 300 mg, sodium salicylate, 500 mg, or a combination of sodium salicylate 500 mg followed by aspirin 300 mg 1 1/2 or 3 hr later. Aspirin alone substantially reduced PGI2 synthesis but sodium salicylate alone had no effect. Sodium salicylate administration prior to aspirin did not reverse the inhibitory effect of aspirin on PGI2 synthesis.
Prostacyclin Synthesis Is Stimulated by a Serum Factor Formed During Coagulation
Authors: Ritter J M , Ongari M-A , Orchard M A , Lewis P J 
Published: July 2018

SummaryFresh aortic rings incubated in serum produce more 6-oxo-PGF1α, the stable hydrolysis product of prostacyclin, than in plasma or buffer. A method is described of recovering this stimulatory activity from a dialysate of serum, showing that the activity is due to a prostacyclin stimulating factor. This factor is formed during coagulation initiated by the intrinsic pathway but not by the extrinsic pathway or by thrombin. By contrast with a previously described plasma factor, the activity of the prostacy-clinstimulating factor in serum is not greater in serum from patients with renal failure than from healthy controls. The stimulating factor is antagonised by heparin, but differs in other ways from previously described platelet derived stimulating factor(s).
Platelets Stimulate Thromboplastin Synthesis in Human Endothelial Cells
Authors: Johnsen U L H , Lyberg T , Galdal K S , Prydz H 
Published: July 2018

SummaryHuman umbilical vein endothelial cells in culture synthesize thromboplastin upon stimulation with phytohaemagglutinin (PHA) or the tumor promotor 12-O-tetradecanoyl-phorbol-13-acetate (TPA). The thromboplastin activity is further strongly enhanced in a time dependent reaction by the presence of gel-filtered platelets or platelet aggregates. This effect was demonstrable at platelet concentrations lower than those normally found in plasma, it may thus be of pathophysiological relevance. The thromboplastin activity increased with increasing number of platelets added. Cycloheximide inhibited the increase, suggesting that de novo synthesis of the protein component of thromboplastin, apoprotein III, is necessary.When care was taken to remove monocytes no thromboplastin activity and no apoprotein HI antigen could be demonstrated in suspensions of gel-filtered platelets, platelets aggregated with thrombin or homogenized platelets when studied with a coagulation assay and an antibody neutralization technique.
The Half Life of Factor XIII in the Management of Inherited Deficiency
Authors: Fear J D , Miloszewski K J A , Losowsky M S 
Published: July 2018

SummaryFollowing the injection of a large dose of factor XIII concentrate the in vivo half life of factor XIII was estimated in a patient with inherited deficiency. Factor XIII activity and enzyme concentration were measured quantitatively, and a qualitative assessment of the crosslinking of fibrin was also made for upto 6 weeks after the injection. The half life was found to be about 9-10 days. This is longer than most previous reports suggest. An explanation for this finding is offered. The relevance of the long half life of factor XIII to the prophylactic treatment of patients with inherited deficiency is demonstrated.
Factors Influencing the Deaggregation of Chymotrypsin-Treated Human Platelets Aggregated by Fibrinogen
Authors: Kinlough-Rathbone R L , Mustard J F , Packham M A , Harfenist E J 
Published: July 2018

SummaryWashed human platelets aggregated by ADP can be deaggregated by EDTA or PGE1; provided the release reaction does not occur; when the release reaction occurs platelets deaggregate less readily. Platelets treated with chymotrypsin are aggregated by fibrinogen indicating that fibrinogen receptors may be permanently exposed by this treatment. Fibrinogen-induced aggregation of chymotrypsin-treated platelets provides another method of bringing platelets into close contact with each other. Although EDTA deaggregated chymotrypsin-treated platelets aggregated by fibrinogen in a medium containing a physiological concentration of Ca2+, EDTA did not deaggregate these platelets if they were in a medium without calcium in which the release reaction occurs. In this medium, when ASA was added to prevent the release reaction, EDTA caused deaggregation. More fibrinogen associated with platelets in the medium without calcium than in the calcium-containing medium. In both media, EDTA displaced approximately half of the fibrinogen indicating that deaggregation is not solely dependent on dissociation of fibrinogen from its receptors. Thus when platelets undergo the release reaction, a form of platelet-to-platelet adhesion occurs that is not disrupted by chelation of divalent cations and is therefore not likely to involve only fibrinogen or thrombospondin and fibrinogen since the association of fibrinogen with its receptor requires Ca2+ and the binding of thrombospondin to platelets that have undergone the release reaction is also dependent on Ca2+.
Influence of Plasma Fibronectin on the Response to Infusion of Thrombin and Adenosine Diphosphate
Authors: Kaplan J E , Snedeker P W , Baum S H , Moon D G , Minnear F L 
Published: July 2018

SummaryAn important physiological anti-thrombotic function has been suggested for plasma fibronectin and the reticuloendothelial system. The current study evaluated the effects of specific immunological fibronectin depletion and fibronectin supplementation upon resistance to infusion of thrombin and ADP in terms of mortality, mean arterial blood pressure and circulating levels of platelets, fibrinogen and fibrin degradation products. Mortality data indicated that rats with reduced fibronectin levels had reduced resistance to thrombin or adenosine diphosphate infusion. The increased lethality was characterized by reduced circulating levels of fibrinogen and platelets while fibrin degradation product levels rose. The infusion of ADP or thrombin in fibronectin supplemented rats failed to elicit higher mortality or reduce fibrinogen or platelet levels further. These data are consistent with the hypothesis that resistance to excessive coagulation and/or platelet aggregation is correlated to circulating plasma fibronectin levels. It is suggested that by direct effects and/ or acting as an opsonin for RES phagocytosis, plasma fibronectin acts as an important anti-thrombotic mechanism.
A Standardized Method for Measuring Anti-F VIII:C Inhibitors in Haemophilia A by Coagulation Inhibition in Agarose Gel
Authors: Jorquera J I , Carmona E , Aznar J A , Peiró A , Sánchez-Cuenca J M 
Published: July 2018

SummaryAntibodies against factor-VIII coagulant activity can appear in haemophilic patients and, although infrequently, can affect individuals not suffering from Haemophilia A. The Oxford and Bethesda methods are presently the most commonly used techniques for measuring these antibodies. Both methods are time-consuming and not suitable for the screening of large risk groups.An appropriate method for screening these coagulation inhibitors is that described by P. Bird in 1975. It is based on inhibition of the coagulation produced when plasma samples containing inhibitors diffuse in agarose gels mixed with normal platelet rich plasma (PRP). However, this technique is highly dependent on the variability derived from the use of PRP (amount of coagulant factor-VIII, number of platelets, etc.).In an attempt to avoid these disadvantages, Bird’s method has been modified by using standardized commercial reagents (lyophilized plasma with 100% factor-VIII coagulant activity, purified fibrinogen, and platelet Factor 3) instead of PRP. The sensitivity reaches 0.8 Bethesda units and the correlation with the Bethesda method is r = 0.964, p <0.001. This newly developed method is as simple as Bird’s, and appears to be at least, as accurate and reproducible as the Bethesda method.
Fibrinogen Bergamo I (Aα16Arg → Cys): Susceptibility Towards Thrombin Following Aminoethylation, Methylation or Carboxamidomethylation of Cysteine Residues
Authors: Reber P , Furlan M , Beck E A , Finazzi G , Buelli M , Barbui T 
Published: July 2018

SummaryAn abnormal fibrinogen, denoted as “fibrinogen Bergamo I”, has been characterized. Its defect consists in an exchange of arginine by cysteine in position 16 of the Aα-chain, thus corresponding to that found in a number of other fibrinogen variants. The abnormal fibrinopeptide A cannot be split off by thrombin from intact fibrinogen Bergamo I. We describe three different chemical modifications of the cysteine Aαl6, i.e. aminoethylation, methylation and carboxamidomethylation, and their effects on the susceptibility of fibrinogen Bergamo I towards thrombin attack. S-aminoethylation of the Aαl6Cys renders the peptide bond Aαl6–17 cleavable by thrombin. Following methylation or carboxamidomethylation, the Aαl9-arginyl bond becomes accessible for thrombin. The chemically modified extended fibrinopeptide A can be readily separated from the normal fibrinopeptide A by HPLC. The latter two modifications are suitable alternative procedures for detecting the molecular defect Aαl6Arg → Cys of fibrinogen.
Antithrombin III Activity and Concentration in Diabetes Mellitus
Authors: Patrassi G M , Picchinenna R , Vettor R , Cappellato G , Coccarielli D , Girolami A 
Published: July 2018

SummaryAntithrombin III (AT III) levels have been reported to be low, normal, and high in diabetes mellitus. Furthermore, a dicrepancy between AT III activity and antigen concentration was reported. We have evaluated the behaviour of AT III activity and antigen level both in type 1 and type 2 diabetes, either in uncontrolled or in well controlled patients. AT III activity and antigen levels showed values similar to normal. No difference was seen between type 1 and type 2 diabetes. Similar results were observed in the group of well controlled diabetic patients. AT III activity and antigen did not correlate with blood glucose and glycosylated haemoglobin (HbA1). No difference was observed between AT III activity and antigen levels in any group. Therefore the hypercoagulable state found in diabetes mellitus does not depend on AT III modifications. A discrepancy between AT III activity and antigen was not confirmed. A dysantithrombinaemia, explained on the basis of an inactivation of protein glycosylation in diabetes mellitus has not been confirmed.
Inhibition of Platelet Aggregation by Human Placenta
Authors: Dembélé-Duchesne M J , Lahlou A Laghchim , Thaler-Dao H , de Paulet A Crastes 
Published: July 2018

SummaryHuman placental cytosol inhibits platelet aggregation induced by high doses of collagen. The aim of this study was to investigate whether this anti-aggregating activity was caused only by the presence of various activities already described in the placenta (an ADP-consuming enzyme, a fatty acid cyclooxygenase inhibitor, and a thromboxane synthetase inhibitor) or whether another factor was present.Heating the cytosol at 50° C for 6 min destroyed the inhibitor of collagen-induced aggregation. ADPase and the AA pathway inhibitors were not modified by this treatment. We therefore show the presence of an additional anti-aggregating factor: it is destroyed by heating at 50° C.We also tested for the presence of an inhibitor of AA release in the placental cytosol using three different methods (rabbit platelets in PRP, washed rabbit platelets, and NRK fibroblasts) but no inhibition could be evidenced.We conclude that this new anti-aggregating factor, which is probably a protein, acts neither through AA release inhibition nor AA cascade inhibition.
Increased Euglobulin Fibrinolytic Potential in Women on Oral Contraceptives Low in Oestrogen – Levels of Extrinsic and Intrinsic Plasminogen Activators, Prekallikrein, Factor XII, and C1-Inactivator
Authors: Jespersen Jørgen , Kluft Cornelis 
Published: July 2018

SummaryComponents of the fibrinolytic system were studied in samples of plasma from 15 normal, young women and from 11 women taking oral contraceptives containing 30 μg ethinyl oestradiol and 150 μg levo-norgestrel. Fibrinolytic activity of euglobulins precipitated at pH 5.9 was higher than normal in the hormone group, with significant fluctuations related to the cycle. Normal women showed only minor fluctuations. The concentration of C1-inactivator was lower in euglobulins of the hormone group. However, the difference in fibrinolytic activity was retained, when C1-inactivator was inactivated with sodium flufenamate. Fluctuations of the extrinsic (tissue-type) plasminogen activator (t-PA) activity parallelled those of the euglobulin activity.The intrinsic plasminogen activator activity (dextran sulphate precipitated euglobulin) was significantly increased in the hormone group and the cyclic pattern differed from that of the normal group. The increased activity was factor XII-dependent. Plasma prekallikrein did not differ. The factor XII level was increased in the hormone group but this could not explain the increased intrinsic fibrinolytic activity, suggesting an increase in the quantity of an additional factor XII-dependent proactivator.
Carrier Detection of Haemophilia B by Using an Intragenic Restriction-Fragment Length Polymorphism
Authors: Bröcker-Vriends A H. J. T , Briët E , Quadt R , Bertina R M , van der Linden I K , van de Kamp J J P , Pearson P L , Veltkampt J J 
Published: July 2018

SummaryWe analysed DNA from individuals of five families with haemophilia B, including nineteen potential carriers. A genespecific probe was used to reveal a TaqI restriction-fragment length polymorphism. Segregation analysis of the polymorphic marker and the deleterious mutation within families allowed diagnosis at the gene level for 16 out of the 19 potential carriers, two proving to be carriers and 14 non-carriers. The obvious advantage is that lyonisation, which is a limiting factor when gene product (clotting factor IX) measurements are used for carrier detection, does not interfere with this procedure and that the result is a definitive diagnosis instead of a risk estimate. The method also permits prenatal diagnosis on chorionic villi in the first trimester of pregnancy.Restriction-fragment length analysis, based upon the probe and restriction enzyme used in this study, will be informative for approximately 45% of the individuals at risk of carrying or transmitting the haemophilia B mutation.
Enhancement of Factor VIII-von Willebrand Factor Ristocetin Cofactor Activity by Monoclonal Antibodies
Authors: Hornsey V , Micklem L R , McCann M C , James K , Dawes J , McClelland D B L , Prowse C V 
Published: July 2018

SummaryFive monoclonal antibodies to human von Willebrand factor were selected for characterization from 18 produced in murine hybridomas. All showed a high and specific affinity for human von Willebrand factor (vWf) but exhibited little if any crossreaction with sera from other species. The antibodies defined four epitopes on vWf, none of which were involved in platelet binding. Binding of two distinct antibodies at one of these epitopes was associated with enhancement of the rate of vWf-dependent platelet agglutination in the presence of ristocetin. This effect was more noticeable when cryosupernatant plasma was used in place of normal plasma as the source of vWf, and was not explicable simply in terms of antibody-induced cross-linking of vWf.