Clinical studies with oral lipid based formulations of poorly soluble compounds

This work is an attempt to give an overview of the clinical data available on lipid based formulations. Lipid and surfactant based formulations are recognized as a feasible approach to improve bioavailability of poorly soluble compounds. However not many clinical studies have been published so far. Several drug products intended for oral administration have been marketed utilizing lipid and surfactant based formulations. Sandimmune® and Sandimmune Neoral® (cyclosporin A, Novartis), Norvir® (ritonavir), and Fortovase® (saquinavir) have been formulated in self-emulsifying drug delivery systems (SEDDS). This review summarizes published pharmacokinetic studies of orally administered lipid based formulations of poorly aqueous soluble drugs in human subjects. Special attention has been paid to the physicochemical characteristics of the formulations, when available and the impact of these properties on the in vivo performance of the formulation. Equally important is the effect of concurrent food intake on the bioavailability of poorly soluble compounds. The effect of food on the bioavailability of compounds formulated in lipid and surfactant based formulations is also reviewed

Finding an egg in a haystack: variation in chemical cue use by egg parasitoids of herbivorous insects

Egg parasitoids of herbivorous insects use an interplay of short -and long-range chemical cues emitted by hosts and host plants to find eggs to parasitize. Volatile compounds that attract egg parasitoids can be identified via behavioral assays and used to manipulate parasitoid behavior in the field for biological control of herbivorous pests. However, how and when a particular cue will be used varies over the life of an individual, as well as at and below species level. Future research should expand taxonomic coverage to explore variation in chemical cue use in more natural, dynamic settings. More nuanced understanding of the variability of egg parasitoid host-finding strategies will aid in disentangling the underlying genetics and further enhancing biological control

The role of comptetitors for Chrysomela lapponica, a north Eurasian willow pest, in pioneering a new host plant

The Palaearctic leaf beetle Chrysomela lapponica usually feeds upon willows in the northern region of its occurrence. However, in Central Europe, some populations are known that have specialised on birch. In this study, we investigated the significance of other herbivores occurring together on the same host plants as possible exploitative competitors of C. lapponica. Two populations were studied: a population from Finland specialised on the willow Salix borealis, and a population from the Czech Republic, specialised on the birch Betula pubescens. Abundances of folivorous and suctivorous insects on both host plants were recorded at both population sites. The willow leaf beetle Phratora vitellinae was the most abundant herbivorous insect at both study sites on willow. A field study was conducted to examine the effects of P. vitellinae on the performance of C. lapponica. The presence of P. vitellinae larvae on the same twig upon which C. lapponica larvae were feeding did not affect increase of body weight in C. lapponica larvae. Thus, the high resource availability of both willows and birches suggest that interspecific competition is unlikely to be a selection factor driving the evolution of host shift in C. lapponica

The Neotropical mirid predator Macrolophus basicornis uses volatile cues to avoid contacting old, Trichogramma pretiosum parasitized eggs of Tuta absoluta

Polyphagous mirid predators are increasingly used in commercial, augmentative biological control. Information about their foraging behaviour is essential, especially if one intends to use several natural enemies to control one or more pests in a crop, to detect if negative intraguild effects occur. We studied a case of intraguild predation (IGP) involving the predator Macrolophus basicornis (Stal) (Hemiptera Miridae) of the worldwide invasive South American tomato leaf miner Tuta absoluta (Meyrick) (Lepidoptera Gelechiidae) and explored how this predator deals with prey parasitized by Trichogramma pretiosum (Riley) (Hymenoptera Trichogrammatidae). Behavioural observations show that M. basicornis predators contacted significantly fewer old, parasitized eggs of T. absoluta than recently parasitized eggs. Olfactometer tests revealed that predators could smell differences between vola-tiles of tomato leaves infested with eggs of different qualities to locate suitable prey. They preferred volatiles from leaflets with unparasitized eggs above control leaflets and, moreover, preferred volatiles from leaflets with recently parasitized eggs over volatiles of leaflets with 5-day-old parasitized eggs. When predators and parasitoids are used together to control T. absoluta, parasitoids should be introduced one week before predators are released to prevent high levels of IGP

The response specificity of Trichogramma egg parasitoids towards infochemicals during host location

Parasitoids are confronted with many different infochemicals of their hosts and food plants during host selection. Here, we investigated the effect of kairomones from the adult host Pieris brassicae and of cues present on Brussels sprout plants infested by P. brassicae eggs on the behavioral response of the egg parasitoid Trichogramma evanescens. Additionally, we tested whether the parasitoid¿s acceptance of P. brassicae eggs changes with different host ages. The wasps did not discriminate between olfactory cues from mated and virgin females or between mated females and males of P. brassicae. T. evanescens randomly climbed on the butterflies, showing a phoretic behavior without any preference for a certain sex. The parasitoid was arrested on leaf parts next to 1-day-old host egg masses. This arrestment might be due to cues deposited during oviposition. The wasps parasitized host eggs up to 3 days old equally well. Our results were compared with former studies on responses by T .brassicae showing that T. evanescens makes less use of infochemicals from P. brassicae than T. brassicae

Intensity of intraguild predation of parasitized eggs by mirid predators depends on time since parasitization: a case study with the parasitoid Trichogramma pretiosum and the predator Macrolophus basicornis attacking Tuta absoluta eggs

Concurrent releases of several species of natural enemies for pest control have been studied in various crops with either positive, neutral, or negative results. To control the pest Tuta absoluta (Meyrick) (Lepidoptera Gelechiidae), only the egg parasitoid Trichogramma pretiosum Riley (Hymenoptera Trichogrammatidae) is applied on many hectares with tomatoes in South America. Use of the mirid predator Macrolophus basicornis Stal (Hemiptera Miridae) is considered either alone or in combination with the parasitoid T. pretiosum. To determine if intraguild relationships between the two natural enemies negatively affect concurrent releases, unparasitized eggs and eggs parasitized by T. pretiosum were exposed to the predator. Knowing which stages of parasitized eggs are consumed or rejected by the predator is important for development of a release strategy resulting in highest pest mortality. M. basicornis consumed 1-2 day old parasitized eggs as well as unparasitized eggs, and, consequently, expressed strong intraguild predation (IGP). Five and 9-day old parasitized eggs were often not consumed, and, therefore, exerted the phenomenon of competitive exclusion (CE). Predation rates of old parasitized eggs were very low and similar in no-choice and choice tests, and in experiments with a large (100), medium (50) and very limited (10) number of preys offered, demonstrating a strong CE effect. Interestingly, in choice experiments with unparasitized and old parasitized eggs, predators started to consume unparasitized eggs significantly later than when only unparasitized or young parasitized eggs were offered. This suggests that old, parasitized eggs in some way reduce the foraging activity of M. basicornis. We expect that stronger pest reduction by concurrent releases of both natural enemies will only occur at the start of the tomato production season and when the egg parasitoid is introduced seven days before the mirid predator in order to reduce intraguild predation of parasitized eggs by the predator

Herbivore-induced plant volatiles mediate in-flight host discrimination by parasitoids

Herbivore feeding induces plants to emit volatiles that are detectable and reliable cues for foraging parasitoids, which allows them to perform oriented host searching. We investigated whether these plant volatiles play a role in avoiding parasitoid competition by discriminating parasitized from unparasitized hosts in flight. In a wind tunnel set-up, we used mechanically damaged plants treated with regurgitant containing elicitors to simulate and standardize herbivore feeding. The solitary parasitoid Cotesia rubecula discriminated among volatile blends from Brussels sprouts plants treated with regurgitant of unparasitized Pieris rapae or P. brassicae caterpillars over blends emitted by plants treated with regurgitant of parasitized caterpillars. The gregarious Cotesia glomerata discriminated between volatiles induced by regurgitant from parasitized and unparasitized caterpillars of its major host species, P. brassicae. Gas chromatography-mass spectrometry analysis of headspace odors revealed that cabbage plants treated with regurgitant of parasitized P. brassicae caterpillars emitted lower amounts of volatiles than plants treated with unparasitized caterpillars. We demonstrate (1) that parasitoids can detect, in flight, whether their hosts contain competitors, and (2) that plants reduce the production of specific herbivore-induced volatiles after a successful recruitment of their bodyguards. As the induced volatiles bear biosynthetic and ecological costs to plants, downregulation of their production has adaptive value. These findings add a new level of intricacy to plant¿parasitoid interaction

The effects of low and high glycemic index foods on exercise performance and beta-endorphin responses

Τhe aim of this study was to examine the effects of the consumption of foods of various glycemic index values on performance, β-endorphin levels and substrate (fat and carbohydrate) utilization during prolonged exercise. Eight untrained healthy males underwent, in a randomized counterbalanced design, three experimental conditions under which they received carbohydrates (1.5 gr. kg-1 of body weight) of low glycemic index (LGI), high glycemic index (HGI) or placebo. Food was administered 30 min prior to exercise. Subjects cycled for 60 min at an intensity corresponding to 65% of VO2max, which was increased to 90% of VO2max, then they cycled until exhaustion and the time to exhaustion was recorded. Blood was collected prior to food consumption, 15 min prior to exercise, 0, 20, 40, and 60 min into exercise as well as at exhaustion. Blood was analyzed for β-endorphin, glucose, insulin, and lactate. The mean time to exhaustion did not differ between the three conditions (LGI = 3.2 ± 0.9 min; HGI = 2.9 ± 0.9 min; placebo = 2.7 ± 0.7 min). There was a significant interaction in glucose and insulin response (P < 0.05) with HGI exhibiting higher values before exercise. β-endorphin increased significantly (P < 0.05) at the end of exercise without, however, a significant interaction between the three conditions. Rate of perceived exertion, heart rate, ventilation, lactate, respiratory quotient and substrate oxidation rate did not differ between the three conditions. The present study indicates that ingestion of foods of different glycemic index 30 min prior to one hour cycling exercise does not result in significant changes in exercise performance, β-endorphin levels as well as carbohydrate and fat oxidation during exercise

Reply to: New Meta- and Mega-analyses of Magnetic Resonance Imaging Findings in Schizophrenia: Do They Really Increase Our Knowledge About the Nature of the Disease Process?

This work was supported by National Institute of Biomedical Imaging and Bioengineering Grant No. U54EB020403 (to the ENIGMA consortium)

Comparing induction at an early and late step in signal transduction mediating indirect defence in Brassica oleracea

The induction of plant defences involves a sequence of steps along a signal transduction pathway, varying in time course. In this study, the effects of induction of an early and a later step in plant defence signal transduction on plant volatile emission and parasitoid attraction are compared. Ion channel-forming peptides represent a class of inducers that induce an early step in signal transduction. Alamethicin (ALA) is an ion channel-forming peptide mixture from the fungus Trichoderma viride that can induce volatile emission and increase endogenous levels of jasmonic acid (JA) and salicylic acid in plants. ALA was used to induce an early step in the defence response in Brussels sprouts plants, Brassica oleracea var. gemmifera, and to study the effect on volatile emission and on the behavioural response of parasitoids to volatile emission. The parasitoid Cotesia glomerata was attracted to ALA-treated plants in a dose-dependent manner. JA, produced through the octadecanoid pathway, activates a later step in induced plant defence signal transduction, and JA also induces volatiles that are attractive to parasitoids. Treatment with ALA and JA resulted in distinct volatile blends, and both blends differed from the volatile blends emitted by control plants. Even though JA treatment of Brussels sprouts plants resulted in higher levels of volatile emission, ALA-treated plants were as attractive to C. glomerata as JA-treated plants. This demonstrates that on a molar basis, ALA is a 20 times more potent inducer of indirect plant defence than JA, although this hormone has more commonly been used as a chemical inducer of plant defence