The present study reports a fast, economical, and feasible way to extract antioxidant phenolics from artichoke byproducts:  raw artichoke (RA), blanched (thermally treated) artichoke (BA), and artichoke blanching waters (ABW). These byproducts represent a huge amount of discarded material in some industries. Two protocols, with possible industrial applicability, based on both methanol and water extractions were used. Phenolic contents (expressed as caffeic acid derivatives) (grams per 100 g of dry extract) were 15.4 and 9.9 for RA when extracted with methanol and water, respectively; 24.3 and 10.3 for BA when extracted with methanol and water, respectively; and finally, 11.3 g of phenolics/100 mL of ABW. Therefore, methanol extracts yielded more phenolics than water extracts, especially when BA byproducts were used. The higher amount of phenolics in BA could be due to the inactivation of polyphenol oxidase (PPO) at the industrial scale (due to blanching process), avoiding PPO-catalyzed oxidation of these ...

Artichoke (Cynara scolymus L.) Byproducts as a Potential Source of Health-Promoting Antioxidant Phenolics

Patient-controlled analgesia (PCA) is a delivery system with which patients self-administer predetermined doses of analgesic medication to relieve their pain. Since its introduction in the early 1980s, the daily management of postoperative pain has been extensively optimised. The use of PCA in hospitals has been increasing because of its proven advantages over conventional intramuscular injections. These include improved pain relief, greater patient satisfaction, less sedation and fewer postoperative complications. All PCA modes contain the following variables: initial loading dose, demand dose, lockout interval, background infusion rate and 1-hour or 4-hour limits. Morphine is the most studied and most commonly used intravenous drug for PCA. In spite of the fact that it is the 'first choice' for PCA, other opioids have been successfully used for this option. The most observed adverse effects of opioid-based PCA are nausea and vomiting, pruritus, respiratory depression, sedation, confusion and urinary retention. Although intravenous PCA is the most studied route of PCA, alternative routes have extensively been described in the literature. PCA by means of peridural catheters and peripheral nerve catheters are the most studied. Recently, transdermal PCA has been described. The use of peripheral or neuraxial nerve blocks is recommended to avoid the so called opioid tolerance observed with the intravenous administration of opioids. Numerous studies have shown the superiority of epidural PCA to intravenous PCA. The beneficial postoperative effects of epidural analgesia are more apparent for high-risk patients or those undergoing higher risk procedures. PCA with peripheral nerve catheters results in increased postoperative analgesia and satisfaction for surgery on upper and lower extremities. Serious complications occur rarely with these catheters. With the introduction of an Acute Pain Service, management of postoperative pain can be improved. This will also help to minimise adverse effects related to PCA and to avoid lethal mishaps.

Patient-Controlled Analgesia in the Management of Postoperative Pain

Uncertainty about the clinical significance of tolerance to opioid analgesia has important and diverse implications. Although understanding of the characteristics and mechanisms of experimental tolerance has grown, the clinical correlates and ramifications of these findings remain ambiguous to practitioners prescribing long-term opioid therapy to patients for the treatment of malignant and non-malignant pain. In this review I shall discuss clinical aspects of tolerance and the associated phenomena of dependence, withdrawal and addiction to opioids as they apply to the practice of clinicians who manage patients with chronic malignant and non-malignant pain.

Opioid tolerance: the clinical perspective

The antioxidant activity of the extracts from Gevuina avellana hulls was evaluated and compared with that of BHT (butylated hydroxytoluene) and BHA (butylated hydroxyanisole), using the beta-carotene bleaching assay, the accelerated oxidation of crude soybean oil, and the 2,2-diphenyl-beta-picrylhydrazyl (DPPH) radical scavenging method. Solvents of different polarity were used to obtain the extracts. Both the extraction yield and the antioxidant activity were strongly dependent on the solvent. The ethanol and diethyl ether soluble fractions were the most active with the beta-carotene assay. Ethanol and methanol extracts were the most active in hydrogen radical scavenging activity. Water and methanol inhibited more efficiently the oxidation of soybean oil at 70 and 80 degrees C, respectively. As a general trend, increased antioxidant activity was observed for increased extract concentration. Except the acetone extracts, all were stable after 6 months storage at 4 degrees C. The ethanol solubles from G. avellana hulls present antioxidant activity similar to that of synthetic antioxidants and to other reported residual agroindustrial materials.

Evaluation of Extracts from Gevuina avellana Hulls as Antioxidants

Opioidergic and dopaminergic modulation of respiration.

Opioid-Agonists and -Antagonists, Opioid-Receptors

Several heterocyclic bicyclo[3.3.1]nonan-9-ones were found to have a high affinity to kappa opioid receptors, 3,7-Diazabicyclononanones with 2,4-dipyridyl side chains were the most potent agonists whereas the corresponding 3-oxa-7-azabicyclo[3.3.1]nonan-9-one and compounds with phenyl substituents in 2 and 4 position are almost inactive. The purpose of this study was to unravel the active conformation of the bicyclononanones using well-known kappa-selective agonists such as ketocyclazocine, arylacetamides, several isoquinolines, CI-977, and four stereoisomers of EMD-61753 for comparison. In order to determine the geometry of the diazabicycles in solution pH-dependent NMR measurements of the bicycles were recorded and the results were related to the geometries of the aforementioned kappa agonists obtained from semiempirical PM3 calculations. A chair-boat conformation and a protonation at the N7 nitrogen atom of the diazabicyclononanones were found to be the pharmacophoric conformation. Comparison of the spatial arrangements, electrostatic, hydrophobic, and hydrogen bonding potentials of all kappa-selective agonists led to a model of structure-activity relationships of ligands of the kappa receptor. The arrangement of the pharmacophoric elements is characterized by an almost parallel orientation of a carbonyl and a protonated NH function in conjunction with at least one aromatic ring. Ketocyclazocine is only able to adopt this parallel orientation when the nitrogen is inverted relative to the X-ray structure. Furthermore, two binding sites for the aromatic rings are discussed. The pharmacological results of all considered bicyclononanone derivatives as well as of the four enantiomers of EMD-61753 can be understood and consistently explained in this way.

Search for the pharmacophore in kappa-agonistic diazabicyclo[3.3.1]nonan-9-one-1,5-diesters and arylacetamides

Die asymmetrische Synthese von optisch aktiven cis-2-Arylcyclohexanaminen 4 wird in einem dreistufigen Verfahren beschrieben: Durch Kondensation der razemischen 2-Arylcyclohexanone 1 mit den chiralen Hilfsaminen R-(+)- bzw. S-(−)-1-Phenylethylamin werden Imin-Isomerengemische 2 erhalten, die nach Hydrierung uber Raney-Nickel ein einziges cis-konfiguriertes sekundares Amin 3 liefern. Hydrogenolyse uber Pd/C fuhrt zu den optisch aktiven primaren cis-2-Arylcyclohexanaminen 4. Die relative Konfiguration sowie die Konformation wurde durch 1H-NMR-Spektroskopie, die absolute Konfiguration der hochgradig enantiomerenreinen Verbindungen 4 mil Hilfe der CD-Spektroskopie bestimmt.



Asymmetric Reductive Amination of Cycloalkanones, VII: Asymmetric Synthesis of cis-1R,2R- and cis-1S,2S-2-Arylcyclohexanamines



The asymmetric synthesis of cis-2-arylcyclohexanamines 4 by a three-step procedure is reported: condensation of racemic 2-arylcyclohexanones 1 with the chiral auxiliary R-(+)- or S-(−)-1-phenylethylamin, respectively, leads to a mixture of the imin isomers 2. Upon hydrogenation with Raney-Nickel just one secondary amin of type 3 is obtained, which is hydrogenolized to the optically active primary cis-2-arylcyclohexanamines 4. The relative configuration as well as the conformation were derived from 1H-NMR data. The absolute configuration of the highly enantiomerically pure compounds 4 was determined by CD spectra.

C. Nachtsheim

Papers

Opioid-Agonists and -Antagonists, Opioid-Receptors

Search for the pharmacophore in kappa-agonistic diazabicyclo[3.3.1]nonan-9-one-1,5-diesters and arylacetamides

Asymmetrische reduktive Aminierung von Cycloalkanonen, 7. Mitt. Die asymmetrische Synthese von cis-1R,2R- und cis-1S,2S-2-Arylcyclohexanaminen

Structurally novel group of ligands selective for kappa opioid receptors

Opioid-agonisten und -antagonisten, opioid-rezeptoren