Search results for "DISCOVERY"

Plasma corticosteroids, free fatty acids, insulin and glucose in maternal blood during delivery.

1970

Plasma-corticosteroids (PCS), free fatty acids (FFA), insulin and glucose were determined continously in maternal blood during the entire course of delivery, from the first stage of labour until 6 hours after delivery. A steep increase in the PCS and FFA concentration could be noticed from the onset of labour (PCS: 37,8±11.2 µg/100 ml;\(s_{\bar x} \),p≦0.01; FFA: 556±106.6 µVal/l;\(s_{\bar x} \),p≦0.01) to the birth of the child (PCS: 96.8±19,5 µg/100 ml;\(s_{\bar x} \),p≦0.01; FFA: 1129±220 µVal/l;\(s_{\bar x} \),p≦0.01) and basal levels were already reached 6 hours later (PCS: 36.0±18.5 µg/100 ml;\(s_{\bar x} \),p≦0.01; FFA: 538±192.8 µVal/l;\(s_{\bar x} \),p≦0.01). The rise of insulin an…

Synthesis and Evaluation of a Novel Series of Pyrrolizine Derivatives as Dual Cyclooxygenase-1 and 5-Lipoxygenase Inhibitors

1997

The aim of our study was to investigate structure activity relationship following the replacement of the 6-phenyl substituent at the 6,7-diaryl-2,3-dihydropyrrolizine template by various heteroaromatic residues. In this context we developed a new, efficient, and highly sensitive test method for the screening of dual cyclooxygenase-1 (COX-1) and 5-lipoxygenase (5-LOX) inhibitors. We used human platelets as a source of COX-1 and human PMNLs as a source of 5-LOX. Both cell types were isolated from the same volume of blood. PGE2 and LTB4 respectively were determined by highly selective and sensitive ELISA kits, using monoclonal antibodies. For a single determination at most 0.5 mL whole blood i…

Non-steroidal Anti-inflammatory Agents, Part 19:E-2-Pyrrolizin-5-yl Acrylic Acids as Potent Dual or Selective Inhibitors of Bovine Cyclooxygenase and…

1995

The pyrrolizinyl substituted acrylic acid derivatives represent another class of dual and selective inhibitors of cyclooxygenase and 5-lipoxygenase. By modifying their substitution pattern at the phenyl moiety of C-6 the balance between the activity against cyclooxygenase and against 5-lipoxygenase can be shifted. Structure-activity relationships are discussed. Compound 6k is the most potent and well-balanced dual inhibitor of both enzymes, while the highest selectivity of lipoxygenase inhibition was found for 6j. The activity and selectivity of compounds with an additional sulfur moiety depend on the oxidation status of this atom, giving an indication of the discussed coupling between pero…

Cyclooxygenase-1/2 (COX-1/COX-2) and 5-lipoxygenase (5-LOX) inhibitors of the 6,7-diaryl-2,3-1H-dihydropyrrolizine type

2003

A series of 6,7-diaryl-2,3-1H-dihydropyrrolizines was prepared as COX-1/COX-2 and 5-LOX inhibitors. The inhibition of COX-1 was evaluated using intact bovine platelets as the enzyme source, whereas LPS-stimulated human monocytes served as the enzyme source for inducible COX-2. The determination of arachidonic metabolites was performed by HPLC for COX-1 and RIA for COX-2. The balance between COX-1/COX-2 and 5-LOX inhibition can be shifted by modifying the substitution pattern of the phenyl moiety at the 6- and 7-position of the pyrrolizine nucleus. Structure-activity relationships are discussed.

COX-1/COX-2 inhibitors based on the methanone moiety

2002

This paper focuses on the synthesis and the in vitro testing of dual COX-1/COX-2 inhibitors. Starting from structures of non-steroidal anti-inflammatory drugs (NSAIDs) the diaryl methanone element was chosen as a lead. Modifications were carried out on this scaffold to obtain potent inhibitors of the COX enzymes. The N-(2-aroylphenyl)sulphonamides and -amides were studied in detail, and to consolidate the data evaluated the corresponding 3- and 4-regioisomers were also investigated. The potency and the enzyme selectivity were varied by structural modifications of the lead.

Spectrofluorimetric Quantification of Malondialdehyde for Evaluation of Cyclooxygenase-1/Thromboxane Synthase Inhibition

1999

The in vitro assay developed by Hartmann and Ledergerber (1995) utilizing the spectrofluorimetric quantification of malondialdehyde after reaction with thiobarbituric acid was modified and used for further investigations. The human whole blood was replaced by a platelet suspension of pig blood, and calcium ionophore A23187 was used instead of collagen for inducing the arachidonic acid cascade. The modified assay represents a simple, time and cost saving method for the evaluation of cyclooxygenase-1/thromboxane synthase inhibition. The reproducibility and comparability of results is given. Additional experiments allow classification of selective phospholipase A2, cyclooxygenase-1, and thromb…

Griffonianone D, an isoflavone with anti-inflammatory activity from the root bark of Millettia griffoniana.

2003

A new isoflavone, griffonianone D (1), and the previously known compounds durmillone and odorantin were isolated from a chloroform extract of the root bark of Millettia griffoniana. The structure of 1 was established as (7E)-(6",7"-dihydroxy-3",7"-dimethyloct-2"-enyl)oxy-4'-methoxyisoflavone on the basis of its spectral data. The chloroform extract of the root bark of M. griffoniana and compound 1 showed anti-inflammatory effects in different experimental models of inflammation.

�ber die Beeinflussung des Weissen Blutbildes Durch die Pteroylglutamins�ure (Fols�ure)

1949

Untersuchungen �ber das Verhalten proteingebundener Sulfhydrylverbindungen des Plasmas bei alternden und katarakt�sen Patienten

1962

Haptoglobin- und Coeruloplasmin-Bestimmungen beim experimentellen Lathyrismus der Ratte

1966

Bei Ratten wurde experimentell durch β-Aminopropionitril Lathyrismus erzeugt. Die beiden Serum-Proteine Haptoglobin und Coeruloplasmin zeigten hinsichtlich ihrer Serum-Spiegelvor undnach der Behandlung keine statistisch signifikanten Unterschiede. Die Peroxydase- und Oxydase-Aktivitat des Ratten-Serums wird demnach durch diese Behandlung nicht verandert. Da der Kohlenhydrat-Anteil des Haptoglobins aus der Grundsubstanz stammen soll, ist demnach durch β-Aminopropionitril keine Veranderung dieses Anteils festzustellen. Das in der Leber synthetisierte Coeruloplasmin erleidet ebenfalls — zumindest quantitativ — keine Veranderungen.