Development, Optimization, and Characterization of Solid Self-Nanoemulsifying Drug Delivery Systems of Valsartan Using Porous Carriers

The present studies entail formulation development of novel solid self-nanoemulsifying drug delivery systems (S-SNEDDS) of valsartan with improved oral bioavailability, and evaluation of their in vitro and in vivo performance. Preliminary solubility studies were carried out and pseudoternary phase diagrams were constructed using blends of oil (Capmul MCM), surfactant (Labrasol), and cosurfactant (Tween 20). The SNEDDS were systematically optimized by response surface methodology employing 3^3-Box–Behnken design. The prepared SNEDDS were characterized for viscocity, refractive index, globule size, zeta potential, and TEM. Optimized liquid SNEDDS were formulated into free flowing granules by adsorption on the porous carriers like Aerosil 200, Sylysia (350, 550, and 730) and Neusilin US2, and compressed into tablets. In vitro dissolution studies of S-SNEDDS revealed 3–3.5-fold increased in dissolution rate of the drug due to enhanced solubility. In vivo pharmacodynamic studies in Wistar rats showed significant reduction in mean systolic BP by S-SNEDDS vis-à-vis oral suspension (p < 0.05) owing to the drug absorption through lymphatic pathways. Solid-state characterization of S-SNEDDS using FT-IR and powder XRD studies confirmed lack of any significant interaction of drug with lipidic excipients and porous carriers. Further, the accelerated stability studies for 6 months revealed that S-SNEDDS are found to be stable without any change in physiochemical properties. Thus, the present studies demonstrated the bioavailability enhancement potential of porous carriers based S-SNEDDS for a BCS class II drug, valsartan.KEY WORDS: BCS, bioavailability, in vitro dissolution, porous carriers, XRD     

Mites as biological tags of their hosts

Movements and spatial distribution of host populations are expected to shape the genetic structure of their parasite populations. Comparing the genetic patterns of both interacting species may improve our understanding of their evolutionary history. Moreover, genetic analyses of parasites with horizontal transmission may serve as indicators of historical events or current demographic processes that are not apparent in the genetic signature of their hosts. Here, we compared mitochondrial variation in populations of the ectoparasitic mite Spinturnix myoti with the genetic pattern of its host, the Maghrebian bat Myotis punicus in North Africa and in the islands of Corsica and Sardinia. Mite mitochondrial differentiation among populations was correlated with both host mitochondrial and nuclear differentiation, suggesting spatial co‐differentiation of the lineages of the two interacting species. Therefore our results suggest that parasite dispersal is exclusively mediated by host movements, with open water between landmasses as a main barrier for host and parasite dispersal. Surprisingly the unique presence of a continental European mite lineage in Corsica was inconsistent with host phylogeographical history and strongly suggests the former presence of European mouse‐eared bats on this island. Parasites may thus act as biological tags to reveal the presence of their now locally extinct host.     

A rapid method for preparation of the cerebrospinal fluid proteome

The cerebrospinal fluid (CSF) proteome is of great interest for investigation of diseases and conditions involving the CNS. However, the presence of high‐abundance proteins (HAPs) can interfere with the detection of low‐abundance proteins, potentially hindering the discovery of new biomarkers. Therefore, an assessment of the CSF subproteome composition requires depletion strategies. Existing methods are time consuming, often involving multistep protocols. Here, we present a rapid, accurate, and reproducible method for preparing the CSF proteome, which allows the identification of a high number of proteins. This method involves acetonitrile (ACN) precipitation for depleting HAPs, followed by immediate trypsination. As an example, we demonstrate that this method allows discrimination between multiple sclerosis patients and healthy subjects.     

Two new species of Agatea (Violaceae) endemic to New Caledonia, with some taxonomic notes and a key to New Caledonian species

While working on a treatment of Violaceae for the Flore de Nouvelle-Caledonie et dependences , two new species were recognized, Agatea veillonii Munzinger and A. lecointei Munzinger. These species are here described and illustrated. Some taxonomic notes and a regional identification key are provided.     

Theory and practice of combining coagulant fixation and microwave histoprocessing

The German, F. Blum, introduced formalin as a fixative in 1893. Formalin rapidly became popular for hardening and preserving gross human and animal specimens. As a result, microscopy for diagnostic pathology by combining paraffin embedding and formalin fixation was developed. Alcohol-based fixatives have coagulation of proteins as their main preservative effect. Because there is no cross-linking, immunostaining is not compromised, and DNA and RNA is not damaged. Ethyl alcohol was used by Dutch scientists of the 18th century, but was replaced by the cheaper formalin. Addition of low molecular weight polyethylene glycol (PEG) optimized the coagulant fixative, Kryofix. The polyethylene glycol prevents excessive hardening and enhances the speed of coagulation of proteins. Kryofix was used on a large scale for skin biopsies in Leiden between 1987 and 2001. DNA preservation by the formulated coagulant fixative, BoonFix, is related to the concentration of ethyl alcohol, PEG and acetic acid. BoonFix has been used since 2004 in Leiden for over 40,000 diagnostic skin biopsies and more than 100,000 cervical samples. A literature review and three decades of experience with coagulant, formalin-free fixatives in pathology suggest that when health authorities realize that formalin invalidates expensive tests, it might eventually be eliminated legislatively from diagnostic pathology. Finally, coagulant fixation is optimal for microwave histoprocessing where ethyl alcohol is followed by isopropanol.     

Circular Bacteriocins: Biosynthesis and Mode of Action

Circular bacteriocins are a group of N-to-C-terminally linked antimicrobial peptides, produced by Gram-positive bacteria of the phylum Firmicutes. Circular bacteriocins generally exhibit broad-spectrum antimicrobial activity, including against common food-borne pathogens, such as Clostridium and Listeria spp. These peptides are further known for their high pH and thermal stability, as well as for resistance to many proteolytic enzymes, properties which make this group of bacteriocins highly promising for potential industrial applications and their biosynthesis of particular interest as a possible model system for the synthesis of highly stable bioactive peptides. In this review, we summarize the current knowledge on this group of bacteriocins, with emphasis on the recent progress in understanding circular bacteriocin genetics, biosynthesis, and mode of action; in addition, we highlight the current challenges and future perspectives for the application of these peptides.     

Molecular systematics of the caracaras and allies (Falconidae: Polyborinae) inferred from mitochondrial and nuclear sequence data

The Polyborinae is the most diverse subfamily of the Falconidae in terms of both morphology and behaviour, and includes falconet‐shaped birds (Spiziapteryx), arboreal omnivores (Daptrius, Ibycter), as well as terrestrial generalists and scavengers (Caracara, Milvago and Phalcoboenus). The Polyborinae are endemic to the New World, with all but one species (Caracara cheriway) being restricted to Central and South America. Using over 7300 bp of mitochondrial and nuclear sequence data, we aim to clarify the taxonomy and biogeography of the Polyborinae. The genus Milvago was unexpectedly found to be polyphyletic, with Chimango Caracara Milvago chimango being related to the genus Phalcoboenus and Yellow‐headed Caracara Milvago chimachima being sister to Daptrius. Furthermore, very low genetic divergence was found among the four species of the genus Phalcoboenus, with the lowest divergence being between White‐throated Caracara Phalcoboenus albogularis and Mountain Caracara Phalcoboenus megalopterus. Our divergence time analyses revealed that the Polyborinae started to diversify in the Miocene, at about 14 Ma, and that the generalist/scavenger behaviour in the Falconidae appeared between 14 and 6.6 Ma. All speciation events within the caracaras occurred during the Pleistocene. This situation differs from the general pattern described for forest birds, in which most diversification events are older, occurring primarily in the Pliocene and Miocene.     

PANEL PERFORMANCE AND NUMBER OF EVALUATIONS IN A DESCRIPTIVE SENSORY STUDY

The assessor performance is a key point in a sensory evaluation. In particular, at the end of a session, a decrease of the performance can be feared. We propose to analyze this performance with various criteria: usual ones as the main product effect or the error variance; a new one measuring the perceived products variability. The performance can then be studied all along the session from two points of view: in taking into account the only products tested at a given instant (named instantaneous); in taking into account all the products tested up to a given instant (named cumulative). In the presented example, in spite of the large number of products successively tested by each assessor, the instantaneous performance of the panel shows no significant deterioration. Furthermore, when the number of products tested by each assessor increases, more significant product effects can be obtained thanks to the accumulation of the amount of data. This shows that the number of products that can be reasonably studied by one assessor during one session is generally underestimated.     

The relationship of aerobic capacity,anaerobic peak power and experience to performance in CrossFit exercise

CrossFit is becoming increasingly popular as a method to increase fitness and as a competitive sport in both the Unites States and Europe. However, little research on this mode of exercise has been performed to date. The purpose of the present investigation involving experienced CrossFit athletes and naïve healthy young men was to investigate the relationship of aerobic capacity and anaerobic power to performance in two representative CrossFit workouts: the first workout was 12 minutes in duration, and the second was based on the total time to complete the prescribed exercise. The participants were 32 healthy adult males, who were either naïve to CrossFit exercise or had competed in CrossFit competitions. Linear regression was undertaken to predict performance on the first workout (time) with age, group (naïve or CrossFit athlete), VO₂max and anaerobic power, which were all significant predictors (p < 0.05) in the model. The second workout (repetitions), when examined similarly using regression, only resulted in CrossFit experience as a significant predictor (p < 0.05). The results of the study suggest that a history of participation in CrossFit competition is a key component of performance in CrossFit workouts which are representative of those performed in CrossFit, and that, in at least one these workouts, aerobic capacity and anaerobic power are associated with success.