Superhydrophobicity and size reduction enabled Halobates (Insecta: Heteroptera, Gerridae) to colonize the open ocean.

Despite the remarkable evolutionary success of insects at colonizing every conceivable terrestrial and aquatic habitat, only five Halobates (Heteroptera: Gerridae) species (~0.0001% of all known insect species) have succeeded at colonizing the open ocean - the largest biome on Earth. This remarkable evolutionary achievement likely required unique adaptations for them to survive and thrive in the challenging oceanic environment. For the first time, we explore the morphology and behavior of an open-ocean Halobates germanus and a related coastal species H. hayanus to understand mechanisms of these adaptations. We provide direct experimental evidence based on high-speed videos which reveal that Halobates exploit their specialized and self-groomed body hair to achieve extreme water repellence, which facilitates rapid skating and plastron respiration under water. Moreover, the grooming behavior and presence of cuticular wax aids in the maintenance of superhydrophobicity. Further, reductions of their body mass and size enable them to achieve impressive accelerations (~400 ms-2) and reaction times (~12 ms) to escape approaching predators or environmental threats and are crucial to their survival under harsh marine conditions. These findings might also inspire rational strategies for developing liquid-repellent surfaces for drag reduction, water desalination, and preventing bio-fouling.

Consecutive aquatic jump-gliding with water-reactive fuel.

Robotic vehicles that are capable of autonomously transitioning between various terrains and fluids have received notable attention in the past decade due to their potential to navigate previously unexplored and/or unpredictable environments. Specifically, aerial-aquatic mobility will enable robots to operate in cluttered aquatic environments and carry out a variety of sensing tasks. One of the principal challenges in the development of such vehicles is that the transition from water to flight is a power-intensive process. At a small scale, this is made more difficult by the limitations of electromechanical actuation and the unfavorable scaling of the physics involved. This paper investigates the use of solid reactants as a combustion gas source for consecutive aquatic jump-gliding sequences. We present an untethered robot that is capable of multiple launches from the water surface and of transitioning from jetting to a glide. The power required for aquatic jump-gliding is obtained by reacting calcium carbide powder with the available environmental water to produce combustible acetylene gas, allowing the robot to rapidly reach flight speed from water. The 160-gram robot could achieve a flight distance of 26 meters using 0.2 gram of calcium carbide. Here, the combustion process, jetting phase, and glide were modeled numerically and compared with experimental results. Combustion pressure and inertial measurements were collected on board during flight, and the vehicle trajectory and speed were analyzed using external tracking data. The proposed propulsion approach offers a promising solution for future high-power density aerial-aquatic propulsion in robotics.

Surface proteomics on nanoparticles: a step to simplify the rapid prototyping of nanoparticles.

Engineered nanoparticles for biomedical applications require increasing effectiveness in targeting specific cells while preserving non-target cells' safety. We developed a surface proteomics method for a rapid and systematic analysis of the interphase between the nanoparticle protein corona and the targeted cells that could implement the rapid prototyping of nanomedicines. Native nanoparticles entering in a protein-rich liquid medium quickly form a macromolecular structure called protein corona. This protein structure defines the physical interaction between nanoparticles and target cells. The surface proteins compose the first line of interaction between this macromolecular structure and the cell surface of a target cell. We demonstrated that SUSTU (SUrface proteomics, Safety, Targeting, Uptake) provides a qualitative and quantitative analysis from the protein corona surface. With SUSTU, the spatial dynamics of the protein corona surface can be studied. Data from SUSTU would ascertain the nanoparticle functionalized groups exposed at a destiny that could circumvent preliminary in vitro experiments. Therefore, this method could implement in the analysis of nanoparticle targeting and uptake capability and could be integrated into a rapid prototyping strategy which is a major challenge in nanomaterials science. Data are available via ProteomeXchange with the identifier PXD004636.

Molecular determinants of positive allosteric modulation of the human metabotropic glutamate receptor 2.

BACKGROUND AND PURPOSE: The activation of the metabotropic glutamate receptor 2 (mGlu2 ) reduces glutamatergic transmission in brain regions where excess excitatory signalling is implicated in disorders such as anxiety and schizophrenia. Positive allosteric modulators (PAMs) can provide a fine-tuned potentiation of these receptors' function and are being investigated as a novel therapeutic approach. An extensive set of mutant human mGlu2 receptors were used to investigate the molecular determinants that are important for positive allosteric modulation at this receptor. EXPERIMENTAL APPROACH: Site-directed mutagenesis, binding and functional assays were employed to identify amino acids important for the activity of nine PAMs. The data from the radioligand binding and mutagenesis studies were used with computational docking to predict a binding mode at an mGlu2 receptor model based on the recent structure of the mGlu1 receptor. KEY RESULTS: New amino acids in TM3 (R635, L639, F643), TM5 (L732) and TM6 (W773, F776) were identified for the first time as playing an important role in the activity of mGlu2 PAMs. CONCLUSIONS AND IMPLICATIONS: This extensive study furthers our understanding of positive allosteric modulation of the mGlu2 receptor and can contribute to improved future design of mGlu2 PAMs.

Ant communities (Hymenoptera: Formicidae) in an urban ecosystem near the Atlantic Rainforest

The relationships between an urban ecosystem located near the Atlantic Rainforest in southeastern Brazil and ant communities were studied with the objective of quantifying the ant richness and abundance in the household environment and its surroundings. Eighty residences were sampled, where 58 species and 28 genera pertaining to 7 sub-families were found to be present. Inside the residences, the species richness was found to be lower (26), although the abundance was greater (10,670), with the wash area and kitchen being the locales that contributed with the greatest number of hits. The opposite was true in the areas outside the residences, where 54 species and 3,747 ants were observed. Inside houses, the species known as Tramp ants were found, in the following order of importance: Solenopsis -saevissima, Tapinoma melanocephalum, Linepithema humile, Paratrechina fulva, Wasmannia -auropunctata, P. -longicornis, Pheidole megacephala, Monomorium pharaonis and M. floricola. Externally, mainly in the yards and gardens, species such as Octostruma rugifera, Heteroponera dolo, Hypoponera sp.1 and sp.6, Gnamptogenys sp. 4, G. striatula, Odontomachus meinerti, Pachycondyla constricta and P. striata were found. In general, a greater number of species and lower abundance of individuals were observed in the neighborhoods nearer the mountains than in those closer to the urban center.

A relação entre um ecossistema urbano localizado próximo à Mata Atlântica na região sudeste do Brasil e as comunidades de formigas foi estudada com o objetivo de quantificar a riqueza e a abundância de formigas no interior e no entorno das residências. Oitenta casas foram amostradas, tendo sido encontradas 58 espécies e 28 gêneros pertencentes a 7 subfamílias. No interior das residências foi encontrada uma baixa riqueza de espécies (26) e um alto número de indivíduos (10.670), sendo a área de serviço e a cozinha os locais que mais contribuíram para esse resultado. Já no entorno das residências foram encontradas 54 espécies e 3.747 indivíduos. No interior das casas, as espécies conhecidas como 'Tramp - ants" foram encontradas na seguinte ordem de importância: Solenopsis -saevissima, Tapinoma -melanocephalum, Linepithema humile, Paratrechina fulva, Wasmannia auropunctata, P. longicornis, Pheidole -megacephala, Monomorium pharaonis e M. floricola. Externamente, principalmente no jardim e quintal, foram encontradas espécies como: Octostruma rugifera, Heteroponera dolo, Hypoponera sp.1 e sp.6, Gnamptogenys sp.4, G. -striatula, Odontomachus meinerti, Pachycondyla constricta e P. striata. Em geral, o maior número de espécies e baixa abundância de indivíduos foram observados em bairros próximos às áreas de mata.

Ant communities (Hymenoptera: Formicidae) in an urban ecosystem near the Atlantic Rainforest.

The relationships between an urban ecosystem located near the Atlantic Rainforest in southeastern Brazil and ant communities were studied with the objective of quantifying the ant richness and abundance in the household environment and its surroundings. Eighty residences were sampled, where 58 species and 28 genera pertaining to 7 sub-families were found to be present. Inside the residences, the species richness was found to be lower (26), although the abundance was greater (10,670), with the wash area and kitchen being the locales that contributed with the greatest number of hits. The opposite was true in the areas outside the residences, where 54 species and 3,747 ants were observed. Inside houses, the species known as Tramp ants were found, in the following order of importance: Solenopsis saevissima, Tapinoma melanocephalum, Linepithema humile, Paratrechina fulva, Wasmannia auropunctata, P. longicornis, Pheidole megacephala, Monomorium pharaonis and M. floricola. Externally, mainly in the yards and gardens, species such as Octostruma rugifera, Heteroponera dolo, Hypoponera sp.1 and sp.6, Gnamptogenys sp. 4, G. striatula, Odontomachus meinerti, Pachycondyla constricta and P. striata were found. In general, a greater number of species and lower abundance of individuals were observed in the neighborhoods nearer the mountains than in those closer to the urban center.

Inter- and intralaboratory variation of in vitro diffusion cell measurements: an international multicenter study using quasi-standardized methods and materials.

In vitro measurements of skin absorption are an increasingly important aspect of regulatory studies, product support claims, and formulation screening. However, such measurements are significantly affected by skin variability. The purpose of this study was to determine inter- and intralaboratory variation in diffusion cell measurements caused by factors other than skin. This was attained through the use of an artificial (silicone rubber) rate-limiting membrane and the provision of materials including a standard penetrant, methyl paraben (MP), and a minimally prescriptive protocol to each of the 18 participating laboratories. "Standardized" calculations of MP flux were determined from the data submitted by each laboratory by applying a predefined mathematical model. This was deemed necessary to eliminate any interlaboratory variation caused by different methods of flux calculations. Average fluxes of MP calculated and reported by each laboratory (60 +/- 27 microg cm(-2) h(-1), n = 25, range 27-101) were in agreement with the standardized calculations of MP flux (60 +/- 21 microg cm(-2) h(-1), range 19-120). The coefficient of variation between laboratories was approximately 35% and was manifest as a fourfold difference between the lowest and highest average flux values and a sixfold difference between the lowest and highest individual flux values. Intralaboratory variation was lower, averaging 10% for five individuals using the same equipment within a single laboratory. Further studies should be performed to clarify the exact components responsible for nonskin-related variability in diffusion cell measurements. It is clear that further developments of in vitro methodologies for measuring skin absorption are required.

Determination of clonixin in plasma and urine by reversed-phase high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic method that enables the determination of clonixin in human plasma and urine samples is described. Recovery of the drug was over 87.6 and 80.7% for plasma and urine, respectively. The limit of quantitation of the method was established as 10 ng/ml in plasma and 20 ng/ml in urine samples, with RSDs of less than 11.1%. The applicability of the method was further assessed by determining the plasma concentrations time course of clonixin in six healthy volunteers after single oral dose administration of 150 and 300 mg of clonixin and Clonix.

Dissolution of omeprazole from delayed-release solid oral dosage forms.

The evaluation of the biopharmaceutical quality of omeprazole enteric-coated products (granules in capsules) with respect to its dissolution characteristics is not specifically regulated in any of the most common official pharmacopoeia. USP 23 includes a general monograph for enteric-coated products. This paper reports the evaluation of the medium pH effect on the dissolution rates of omeprazole from four omeprazole-containing products of different manufacturers. It is concluded that the USP 23 recommended dissolution procedure for enteric-coated products is not suitable due to the degradation of omeprazole under such conditions. Furthermore, the medium with pH 8.0 showed different dissolution rates not observed at pH 7.4, allowing discrimination between products of different manufacturers.

Improved bioavailability of a micronized megestrol acetate tablet formulation in humans.

Megestrol acetate, a progestogen widely used in the palliative treatment of endometrial carcinoma and breast cancer, is currently administered orally as a solid dosage form. Bioavailability of the drug following oral administration is closely related to the effectiveness and safety profile of the drug in formulation. Improved immediate-release formulations should allow improved drug delivery into the systemic circulation and, at the end, to the site of action. The micronization of drugs is one of the technological procedures to achieve such a purpose. This paper reports the design and results obtained in an in vivo study of the bioavailability of a micronized megestrol acetate tablet formulation compared to a conventional form. A significant increase in the drug bioavailability was observed, in either the rate or the extent of absorption. In vitro dissolution data of the two study formulations reflected the in vivo findings.

Topical delivery of caffeine from some commercial formulations.

Permeation of caffeine through human skin and artificial membranes (mounted in modified Franz type diffusion cells) was evaluated, either from saturated solutions or from commercially available topical formulations (all containing 3% caffeine). Data interpretation of the caffeine diffusion through human skin does not implicate transfer through pores despite caffeine being a relatively polar molecule. No correlation was found between transfer though the synthetic membranes (cellulose acetate impregnated with isopropyl myristate and silicone rubber soaked in isopropyl myristate) and that observed through skin. The synthetic membranes can be used for assessing product performance in quality assurance but will give little indication of its performance in vivo. The study investigated the percutaneous permeation of caffeine through human skin in order to obtain a mechanistic interpretation of its route of permeation. Synthetic membranes were also examined to determine if they could be used as models for human skin. Different commercial formulations investigated to determine the significance of enhancement strategies.

Bioequivalence evaluation of two omeprazole enteric-coated formulations in humans.

Omeprazole, a proton pump inhibitor, effectively suppresses the gastric acid secretion in the parietal cells of the stomach. Several previously published papers focus on the pharmacokinetics of the drug and its interactions with physiological aspects or with other drugs. The increasing number of omeprazole containing products available in the market, raises questions of therapeutic equivalence and/or generic substitution. The bioequivalence evaluation between two or more formulations provides information about in vivo performance. In a favorable decision regarding bioequivalence, the products are considered to have a similar therapeutic efficacy when used under the same therapeutic conditions. This paper reports the design, results and some important aspects involved in a bioequivalence study between two solid oral formulations from different manufacturers. Some important findings were the high intra-subject variability observed for Cmax and the variability observed between subject profiles, probably caused by the multi-unit type of formulations studied.

Uniformity of dosage units--comparative study of methods and specifications between Eur. Pharm. 3rd and USP 23.

Methods and specifications of Eur. Ph. 3rd Ed. and USP 23 for the evaluation of the uniformity of dosage units were compared, in relation to: (i) allowed dispersion of the sample; and (ii) adequability to control the individual contents of active ingredient in relation to the labelled amount. Using the characteristics of the normal distribution curve, we calculate: (1) the highest dispersion allowable, represented by the relative standard deviation of the uniformity of mass of single-dose preparations of Eur. Ph. 3rd Ed., (results were 3.4, 5.1 and 6.8% for L1 = 5, L = 7.5 and L = 10, respectively); and (2) for all the methods studied the allowable units frequency for different intervals of the labelled amount. Differences between the tests of Eur. Ph. 3rd Ed. and USP 23 can lead to acceptance samples with very different individual contents variability, namely if the limit specifications for the strength was +/- 10%. The main reasons for that are: (1) in Eur. Ph. 3rd Ed., the limits are set with reference to the average content of the sample, and in USP 23, they are set with reference to the labelled amount of the active ingredient; and (2), the USP 23 calculates the content of active ingredient in each tablet from the result of the assay, when the weight variation method was used. Taking +/- 5% of label claim as the specification for the strength of the product, according EEC requirements, the maximum percentage of units outside the range 95-105% of label claim allowed by Eur. Ph. 3rd Ed. and USP 23 tests are similar.

Chronic headaches and sleep disorders.

BACKGROUND: Headaches and sleep problems are common complaints in the daily practice of the general practitioner. Since the relationship between headaches and sleep complaints is complex, clear models of interaction are needed for adequate diagnosis and treatment. METHODS: All subjects, successively seen in a headache clinic during a defined period, were subdivided based on the time of onset of cephalalgia. Subjects who reported onset of headache on a long-term basis, during the nocturnal or early morning (before final awakening) period, were systematically studied by a headache clinic and a sleep disorders center. This subgroup represented 17% of the total headache group. RESULTS: Although the results of the headache clinic study did not differentiate this subgroup from the other patients, the sleep disorders center's interviews and questionnaires demonstrated a significant impact of the sleep disorders on headache and daytime function. Nocturnal monitoring during sleep identified specific sleep disorders in 55% of the subjects with onset of headache during the nocturnal sleep period. Follow-up after treatment of the sleep disorder showed that all subjects with an identifiable sleep disorder reported either an improvement or absence of their headache. The subjects identified with periodic limb movement syndrome were mostly those who reported only an improvement in their sleep and still needed treatment for their headaches. The question of the interaction and association of sleep-related headache and periodic limb movement syndrome is unresolved. CONCLUSION: Headaches occurring during the night or early morning are often related to a sleep disturbance.

Sensitive method for the determination of phenytoin in plasma, and phenytoin and 5-(4-hydroxyphenyl)-5-phenylhydantoin in urine by high-performance liquid chromatography.

An isocratic high-performance liquid chromatographic method is described for the quantitative analysis of phenytoin (PHT) in plasma and both phenytoin and its main metabolite, 5-(4-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) in urine. Following ethyl acetate (plasma) and Extrelut-1 (urine) extraction, samples are analysed by means of a reversed-phase column (Nova-Pak C18), using a mobile phase consisting of methanol-water-tetrahydrofuran (40:60:4, v/v/v) with UV detection at 230 nm. The chromatography is complete in 10 min and the results show good precision (RSD 1.23-4.49%) and sensitivity for a linear range of 0.4-4.0 micrograms ml-1 for PHT in plasma, 0.1-1.0 microgram ml-1 for PHT in urine and 0.1-1.2 microgram ml-1 for p-HPPH in urine. The results indicate the method to be suitable for pharmacokinetic studies.