Volatile Profile in Yogurt Obtained from Saanen Goats Fed with Olive Leaves.

The aim of this study was to evaluate the development of volatile compounds in yogurt samples obtained from goats fed a dietary supplementation with olive leaves (OL). For this purpose, thirty Saanen goats were divided into two homogeneous groups of 15 goats each: a control group that received a standard diet (CG) and an experimental group whose diet was supplemented with olive leaves (OLG). The trial lasted 28 days, at the end of which the milk of each group was collected and used for yogurt production. Immediately after production, and after 7 days of storage at 4 °C in the absence of light, the yogurt samples were characterized in terms of fatty acid profile, oxidative stability and volatile compounds by the solid-phase microextraction (SPME)-GC/MS technique. Dietary OL supplementation positively affected the fatty acid composition, inducing a significant increase in the relative proportion of unsaturated fatty acids, mainly oleic acid (C18:1 cis9) and linolenic acid (C18:3). With regard to the volatile profile, both in fresh and yogurt samples stored for 7 days, the OL supplementation induced an increase in free fatty acids, probably due to an increase in lipolysis carried out by microbial and endogenous milk enzymes. Specifically, the largest variations were found for C6, C7, C8 and C10 free fatty acids. In the same samples, a significant decrease in aldehydes, mainly heptanal and nonanal, was also detected, supporting-at least in part-an improvement in the oxidative stability. Moreover, alcohols, esters and ketones appeared lower in OLG samples, while no significant variations were observed for lactones. These findings suggest the positive role of dietary OL supplementation in the production of goats' milk yogurt, with characteristics potentially indicative of an improvement in nutritional properties and flavor.

Concise synthesis of heliolactone, a non-canonical strigolactone isolated from sunflower.

Heliolactone is one of the earliest identified non-canonical strigolactones. Its concise synthesis was achieved by employing Knoevenagel-type condensation and semi-reduction of a malonate intermediate as the key steps. This synthesis was performed in a non-stereoselective manner, and thus a racemic and diastereomeric mixture of heliolactone was obtained. The developed synthetic route is fairly concise and straightforward.

Extending the Salinilactone Family.

Five new members of the salinilactone family, salinilactones D-H, are reported. These bicyclic lactones are produced by Salinispora bacteria and display extended or shortened alkyl side chains relative to the recently reported salinilactones A-C. They were identified by GC/MS, gas chromatographic retention index, and comparison with synthetic samples. We further investigated the occurrence of salinilactones across six newly proposed Salinispora species to gain insight into how compound production varies among taxa. The growth-inhibiting effect of this compound family on multiple biological systems including non-Salinispora actinomycetes was analyzed. Additionally, we found strong evidence for significant cytotoxicity of the title compounds.

Isolation and Purification of Potent Growth Inhibitors from Piper methysticum Root.

Piper methysticum (kava) root is known to possess promising weed suppressing activity. The present study was conducted to search for potent plant growth inhibitors from the root of this medicinal pepper plant. The ethyl acetate (EtOAc) extract exhibited the strongest reduction on growth of Raphanus sativus (radish) (IC50 shoot and root growth = 172.00 and 51.31 µg/mL respectively) among solvent extracts. From this active extract, nine potent growth inhibitors involved in the inhibitory activities of P. methysticum root were isolated, purified and characterized by column chromatography (CC), gas chromatography-mass spectrometry (GC-MS), electrospray ionization-mass spectrometry (ESI-MS) and nuclear magnetic resonance (NMR). The six fractions purified by CC included two flavanones: 5-hydroxy-4',7-dimethoxyflavanone (C1) and 5,7-dihydroxy-4'-methoxy-6,8-dimethylflavanone (matteucinol, C2) and six kavalactones: 5,6-dehydro-kavain (C3), a mixture of kavain and yagonin (C4), yagonin (C5) and dihydro-5,6-dehydrokavain, 7,8-dihydrokavain, dihydromethysticin and methysticin (C6). The amounts of 5-hydroxy-4',7-dimethoxyflavanone, matteucinol, 5,6-dehydrokavain and yangonin were 0.76, 2.50, 2.75 and 2.09 mg/g dry weight (DW), respectively. The two flavanones C1 and C2 exhibited the strongest inhibition on shoot elongation (IC50 = 120.22 and 248.03 µg/mL, respectively), whilst the two kavalactone mixtures C4 and C6 showed the highest suppression on root growth of R. sativus (IC50 = 7.70 and 15.67 µg/mL, respectively). This study was the first to report the purification and inhibitory activities of the two flavanones 5-hydroxy-4',7-dimethoxyflavanone and matteucinol in P. methysticum root. The isolated constituents from P. methysticum root including the flavanones C1 and C2 and the mixtures C4 and C6 may possess distinct modes of action on plant growth. Findings of this study highlighted that the combinations of hexane-ethyl acetate by 9:1 and 8:2 ratios successfully purified flavanones and kavalactones in P. methysticum root.

[Strigolactones, a novel class of plant hormones controlling branching]. / Les strigolactones, une nouvelle classe d'hormones qui contrôlent la ramification des plantes.

Plant architecture is a major trait for plant survival and plant fitness and has a huge influence on the agronomical value for most crops. The classical theory of apical dominance based on decapitation experiments suggested that two major plant hormones, auxin and cytokinins, were acting antagonistically on bud outgrowth to promote or repress branching. However this theory was challenged in the late 1930's by Snow who suggested the existence of a second messenger to auxin, as auxin was not acting directly to repress branching. The use of branching mutants in pea, Arabidopsis and rice led to the discovery of a new carotenoid-derived signal repressing branching. Genes involved in synthesis (RMS1, RMS5) as well as in response (RMS4) to this new signal have been identified and have given rise to a new model of the branching control. Two independent group have recently shown, one on pea, the other on rice, that strigolactones correspond to this novel signal which represses branching and to the secondary messenger in the theory of apical dominance. Strigolactones have been first identified for their role in germination of parasitic plants like Striga or Orobanche. They also play a critical role in the widespread association between 80% of plants and fungi, the arbuscular mycorrhizal symbiosis, as they are necessary for interaction between certain plants and fungi in the rhizosphere.

Comparing clinician knowledge and online information regarding Alli (Orlistat).

BACKGROUND: Many consumers join online communities focused on health. Online forums are a popular medium for the exchange of health information between consumers, so it is important to determine the accuracy and completeness of information posted to online forums. OBJECTIVE: We compared the accuracy and completeness of information regarding the FDA-approved over-the counter weight-loss drug Alli (Orlistat) from forums and from clinicians. METHODS: We identified Alli-related questions posted on online forums and then posed the questions to 11 primary care providers. We then compared the clinicians' answers to the answers given on the forums. A panel of blinded experts evaluated the accuracy and completeness of the answers on a scale of 0-4. Another panel of blinded experts categorized questions as being best answered based on clinical experience versus review of the literature. RESULTS: The accuracy and completeness of clinician responses was slightly better than forum responses, but there was no significant difference (2.3 vs. 2.1, p=0.5). Only one forum answer contained information that could potentially cause harm if the advice was followed. CONCLUSIONS: Forum answers were comparable to clinicians' answers with respect to accuracy and completeness, but answers from both sources were unsatisfactory.

Embryotoxicity of the artemisinin antimalarials and potential consequences for use in women in the first trimester.

Single oral doses of artesunate, dihydroartemisinin, arteether and artemether administered to rats during a sensitive period of organogenesis caused embryo deaths and malformations (malformed long bones and ventricular septal defects). Extended oral dosing (12 days or more) of monkeys once daily with 12 mg/kg-d artesunate also caused embryo deaths. The initial embryotoxic effect in both species was to kill primitive erythroblasts which are present in the embryo for a few days of gestation in rats and several weeks in primates. The malformations that occurred in rats are attributed to a transient depletion of the primitive erythroblasts. In monkeys, when treatment at 12 mg/kg-d was shortened to 3 or 7 days, the embryos survived but likely suffered a transient loss of primitive erythroblasts. Limited clinical data including 123 first trimester pregnancies have not indicated any adverse effects on pregnancy. However, in rats and monkeys, the embryonic erythroblasts are much more sensitive to artemisinins than are erythroblasts in the adult bone marrow; the latter are indicated by decreases in reticulocyte count. Since decreases in reticulocyte count occur at therapeutic doses in humans, there is reason for concern that any treatment of pregnant women during the putative sensitive period (from approximately postconception Day 21 to approximately postconception week 9) that causes even minor decreases in adult reticulocyte count could also cause a marked depletion of embryonic erythroblasts which could lead to death or malformation of the embryo.

Strategies for the development of novel Taxol-like agents.

Taxol, the first microtubule stabilizer identified, is one of the most important new anticancer drugs to be brought to the clinic in the past 20 yr. The clinical success of TaxolTM led to the development of a second-generation taxane, docetaxel (Taxotere), and multiple third-generation taxane derivatives are under development. Non-taxane microtubule-stabilizers of diverse chemical structures, including the epothilones and discodermolide, show promising preclinical activities and several epothilones are progressing through clinical trials. One important advantage of the new stabilizers is their ability to circumvent drug resistance mechanisms. The clinical development of these new classes of agents suggests that microtubule stabilizers will continue to be important drugs for the treatment of cancer. This chapter provides a brief history of Taxol and the discovery and development status of other classes of microtubule stabilizers. Although all microtubule-stabilizers share similar mechanisms of action, interesting subtle differences among the stabilizers are being detected. This chapter also provides some strategies for identifying the differences among microtubule stabilizers that may help prioritize them for development and clinical use.

Asymmetric synthesis of a chiral building block for cyclopentanoids: a novel enantioselective synthesis of preclavulone A.

A new asymmetric approach to the hydroxylactone (+)-(3aR,4R,6aS)-4-(hydroxymethyl)-3a,4-dihydro-3H-cyclopenta[b]furan-2(6aH)-one (1), a key synthetic building block for cis-1,2-disubstituted five-membered ring derivatives (i.e., isoprostanes, jasmonates, and clavulones), has been described. A remarkable control of the absolute and relative configuration of the three stereocenters was achieved. Thus, the use of the Trost's asymmetric allylic alkylation strategy secured highly enantioenriched (R)-3-(nitromethyl)cyclopent-1-ene (13), which was smoothly converted to (R)-cyclopent-2-enecarboxylic acid (15) in excellent yield and high enantiomeric purity (>98% ee). 6-exo-trig atom-transfer radical cyclizations of ((R)-cyclopent-2-enyl)methyl 2-iodoacetate (12) produced exclusively the desired cis-fused delta-lactone (4aR,7aR)-hexahydro-5-iodocyclopenta[c]pyran-3(1H)-one (11), which was subsequently elaborated to hydroxylactone 1 through a stereocontrolled Pd(II)-mediated lactonization reaction. En route to preclavulone A, a putative elusive intermediate in the biosynthesis of clavulones, the synthetic utility of compound 1 was demonstrated. The key feature in this synthesis was the installation of the lower side chain via the Knochel organozinc sp3-sp C-C coupling protocol.

4-Methylideneisoxazolidin-5-ones--a new class of alpha-methylidene-gamma-lactones with high cytostatic activity.

A novel, general method of synthesis of 4-methylideneisoxazolidin-5-ones 10 is described. The target compounds were synthesized starting from ethyl 2-diethoxyphosphoryl-2-alkenoates 6 or dicyclohexylammonium 4-diethoxyphosphoryl-2-alkenoates 7. Addition of N-methylhydroxylamine hydrochloride to these Michael acceptors, lactonization to 4-diethoxyphosphorylisoxazolidin-5-ones 9, and Horner-Wadsworth-Emmons olefination of formaldehyde using 9 gave the title isoxazolidinones 10. All obtained compounds were tested against L-1210, HL-60, and NALM-6 leukemia cell lines. Several isoxazolidinones 10 were found to be very potent with IC(50)<1 microM. The highest cytostatic activity against HL-60 was observed for 10a and against NALM-6 for 10b with IC(50) values of 0.74 and 0.34 microM, respectively.

The influence of plasticizers on the release of theophylline from microporous-controlled tablets.

The aim of present work was to investigate the influence of plasticizer on the release of theophylline from microporous-controlled tablets. Three plasticizers, acetyltributyl citrate (ATBC), castor oil, and triacetin, were included in this study. These plasticizers reduced the crystallinity of poly(epsilon-caprolactone) (PCL)/poly(ethylene glycol) (PEG)-blended films, and the most prominent change of enthalpy of fusion was the film plasticized by triacetin. This might be due to triacetin penetrating into both PCL and PEG domains. However, the lipophilic property of castor oil only allowed it to alter the crystallization of hydrophobic PCL domain. The Young's modulus and the tensile strength of films showed a decreased tendency while increasing the amount of plasticizer. The change of elongation of plasticized blended films was irregular and was dependent of the type of plasticizer. The size of micropores formed in the presence of plasticizer was larger than those micropores formed in its absence. The fatty plasticizer, castor oil, altered the thermal and mechanical performance and pore size of films via soluble in PCL domain, which resulted in the release of theophylline from castor oil plasticized-coated tablets, which in turn enhanced and closed to a constant release pattern.

Cyclo-oxygenase 2 inhibitors: an important new drug classification.

The pharmacologic treatment of acute and chronic pain has evolved greatly over the last several decades. Notably, several new classifications of drugs have emerged to meet the growing demand of patients in pain and health care providers who attempt to assist them. This article describes 1 new classification, cyclo-oxygenase 2 inhibitors, and provides specifics about the 2 agents currently available via prescription.

Ibuprofen to rofecoxib: what does it all mean and what do I do now?

NSAIDs are used throughout the World Health Organization three-step analgesic ladder, and are indicated for pain in all stages of malignancy. Side-effects are common with NSAIDs. Much has been written about NSAIDs and COX, since the discovery of COX-1 and COX-2 isoforms. How do you choose the appropriate NSAID? The choice of NSAID continues to be dependent upon associated gastroduodenal toxicity and the related risk factors of individual patients. Choosing the appropriate NSAID should minimize the likelihood of needing additional medications to manage adverse effects and symptoms caused by the NSAID therapy itself.

Lipase-catalysed resolution of gamma- and delta-lactones.

Lipase-catalysed stereoselective hydrolysis of a family of saturated gamma- and delta-lactones was investigated. Increasing the chain length from delta-octalactone to delta-dodecalactone leads to higher enantiomeric excess. Best results were found using a lipase from Pseudomonas species (KW51) yielding highest enantiomeric excesses (greater than 99% ee at 50% conversion, E > 100) at short reaction times (10 h) for delta-undecalactone and delta-dodecalactone. In contrast, gamma-lactones were resolved less efficiently. Highest enantioselectivities (70%ee at 50% conversion, E = 11) were found for gamma-nonalactone. Optimum reaction conditions were found at pH 8 and 12.5 degrees C.

New cineromycins and musacins obtained by metabolite pattern analysis of Streptomyces griseoviridis (FH-S 1832). I. Taxonomy, fermentation, isolation and biological activity.

Chemical screening using thin layer chromatography and various staining reagents offers the opportunity to visualize a nearly complete picture of a microbial secondary metabolite pattern (metabolic finger-print). This approach can be used advantageously for both, the detection of so-called "talented" strains, and for qualifying microbial strain collections, especially as a fundamental step of efficiently applied biological high-throughput assays. Based on their metabolic finger-print, microbial isolates can be classified in: (i) non-producing organisms, which gave no indication of the formation of secondary metabolites up to a defined detection limit, (ii) organisms of narrow productivity, which produce one or two secondary metabolites as main products with a restricted dependence to alteration of the culture conditions, and (iii) talented organisms, which are able to synthesize an array of structurally different secondary metabolites. As an example, the talented strain, Streptomyces griseoviridis (FH-S 1832), was studied in detail. Investigations in its taxonomical characterization, fermentation, as well as the isolation and purification procedures leading to 14-membered macrocyclic lactones of the cineromycin-type (cineromycin B and three new congeners) and to the musacins A to F are reported. Musacin C exhibits anthelminthic and weak antiviral activities.

A case for drug treatment of obesity.

Several brain receptor systems can modulate food intake. Thus, in a new strategy against obesity, the patient takes submaximal doses of two drugs that act by differing mechanisms.

Immunomodulatory activity of various fractions derived from Physalis angulata L extract.

The immunomodulatory effects of Physalis angulata L. extract fraction VII (PA-VII), PA-VII-A, PA-VII-B and PA-VII-C were investigated in this study. The results showed that PA-VII and PA-VII-C strongly enhanced blastogenesis response, PA-VII-B had moderate activity, and PA-VII-A exerted only slight effect on cell proliferation. A synergistic effect was observed when the suboptimal dosage of phytohemagglutinin (PHA) or lipopolysaccharide (LPS) was added to the culture. Furthermore, PA-VII and PA-VII-C possessed stimulatory activity on B cells and less effect on T cells. The antibody responses were also augmented by PA-VII, PA-VII-B and PA-VII-C, but not by PA-VII-A. The enhancement of antibody response could be observed both in BALB/c and C3H/HeJ mice.