Design of novel urogenital pharmabiotic formulations containing lactobacilli,salivaricin CRL 1328 and non-microbial compounds with different functionalities

Context: The administration of pharmabiotics is a promising alternative to antimicrobial drugs for the treatment and/or prevention of female urogenital infections.

Objective: To design pharmabiotic formulations including bioactive ingredients of microbial origin combined with non-microbial substances and then to evaluate the stability of the combinations during freeze-drying and storage.

Materials and methods: Different formulations including Lactobacillus gasseri CRL 1263, Lactobacillus salivarius CRL 1328, salivaricin CRL 1328 (a bacteriocin) and non-microbial compounds (lactose, inulin and ascorbic acid) were assayed, and the ingredients were freeze-dried together or separately. The formulations were stored in gelatin capsules at 4?°C for 360?d.

Results: The viability of lactobacilli was affected to different extents depending on the strains and on the formulations assayed. L. salivarius and ascorbic acid were successfully combined only after the freeze-drying process. Salivaricin activity was not detected in formulations containing L. gasseri. However, when combined with ascorbic acid, lactose, inulin or L. salivarius, the bacteriocin maintained its activity for 360?d. The selected microorganisms proved to be compatible for their inclusion in multi-strain formulations together with lactose, inulin and ascorbic acid. Salivaricin could be included only in a L. salivarius CRL 1328 single-strain formulation together with non-microbial substances.

Conclusions: This study provides new insights into the design of urogenital pharmabiotics combining beneficial lactobacilli, salivaricin CRL 1328 and compounds with different functionalities.     

Effects of corticotropin-releasing factor on brain serotonergic activity

The serotonergic dorsal raphe nucleus is innervated by corticotropin-releasing factor (CRF) and expresses CRF receptors, suggesting that endogenous CRF impacts on this system. The present study characterized interactions between CRF and the dorsal raphe serotonin (5-HT) system. The effects of intracerebroventricularly (i.c.v.) administered CRF on microdialysate concentrations of 5-HT in the lateral striatum of freely moving rats were determined. CRF had biphasic effects, with 0.1 and 0.3 microgram decreasing, and 3.0 micrograms increasing 5-HT dialysate concentrations. i.c.v. administration of CRF inhibited neuronal activity of the majority of dorsal raphe neurons at both low (0.3 microgram) and high (3 micrograms) doses. Likewise, intraraphe administration of CRF (0.3 and 1.0 ng) had predominantly inhibitory effects on discharge rate. Together, these results suggest that CRF is positioned to regulate the function of the dorsal raphe serotonergic system via actions within the cell body region. This regulation may play a role in stress-related psychiatric disorders in which 5-HT has been implicated.     

Volume rendering of multimodal images: application to MRI and PET imaging of the human brain

A procedure for combining and visualizing complementary structural and functional information from magnetic resonance imaging (MRI) and positron emission tomography (PET) is described. MR and PET images of the human brain were obtained and correlated to form three-dimensional volumes of image data. Volume rendering and solid-texturing concepts were combined to develop a new volume imaging technique for ;volume texture-mapping' brain glucose metabolism (from PET) onto brain anatomy (from MRI). The technique was used to produce sequences of three-dimensional views: these sequences were dynamically displayed in a ;cine-loop' to better visualize the three-dimensional relationship between brain structure and function. The techniques provide a means of presenting vast amounts of multidimensional data in a form that is easily understood, and the resulting images are essential to an understanding of the normal and pathologic states of the human brain.     

Top-down vs bottom-up methodologies in multi-agent system design

Traditionally, two alternative design approaches have been available to engineers: top-down and bottom-up. In the top-down approach, the design process starts with specifying the global system state and assuming that each component has global knowledge of the system, as in a centralized approach. The solution is then decentralized by replacing global knowledge with communication. In the bottom-up approach, on the other hand, the design starts with specifying requirements and capabilities of individual components, and the global behavior is said to emerge out of interactions among constituent components and between components and the environment. In this paper we present a comparative study of both approaches with particular emphasis on applications to multi-agent system engineering and robotics. We outline the generic characteristics of both approaches from the MAS perspective, and identify three elements that we believe should serve as criteria for how and when to apply either of the approaches. We demonstrate our analysis on a specific example of load balancing problem in robotics. We also show that under certain assumptions on the communication and the external environment, both bottom-up and top-down methodologies produce very similar solutions.

Sorafenib delivery nanoplatform based on superparamagnetic iron oxide nanoparticles magnetically targets hepatocellular carcinoma

Currently,sorafenib is the only systemic therapy capable of increasing overall survival of hepatocellular carcinoma patients.Unfortunately,its side effects,particularly its overall toxicity,limit the therapeutic response that can be achieved.Superparamagnetic iron oxide nanoparticles (SPIONs) are very attractive for drug delivery because they can be targeted to specific sites in the body through application of a magnetic field,thus improving intratumoral accumulation and reducing adverse effects.Here,nanoformulations based on polyethylene glycol modified phospholipid micelles,loaded with both SPIONs and sorafenib,were successfully prepared and thoroughly investigated by complementary techniques.This nanovector system provided effective drug delivery,had an average hydrodynamic diameter of about 125 nm,had good stability in aqueous medium,and allowed controlled drug loading.Magnetic analysis allowed accurate determination of the amount of SPIONs embedded in each micelle.An in vitro system was designed to test whether the SPION micelles can be efficiently held using a magnetic field under typical flow conditions found in the human liver.Human hepatocellular carcinoma (HepG2) cells were selected as an in vitro system to evaluate tumor cell targeting efficacy of the superparamagnetic micelles loaded with sorafenib.These experiments demonstrated that this delivery platform is able to enhance sorafenib's antitumor effectiveness by magnetic targeting.The magnetic nanovectors described here represent promising candidates for targeting specific hepatic tumor sites,where selective release of sorafenib can improve its efficacy and safety profile.     

Template‐Free Fabrication of Mesoporous Alumina Nanospheres Using Post‐Synthesis Water‐Ethanol Treatment of Monodispersed Aluminium Glycerate Nanospheres for Molybdenum Adsorption

This work reports the template‐free fabrication of mesoporous Al₂O₃ nanospheres with greatly enhanced textural characteristics through a newly developed post‐synthesis “water‐ethanol” treatment of aluminium glycerate nanospheres followed by high temperature calcination. The proposed “water‐ethanol” treatment is highly advantageous as the resulting mesoporous Al₂O₃ nanospheres exhibit 2–4 times higher surface area (up to 251 m² g^?1), narrower pore size distribution, and significantly lower crystallization temperature than those obtained without any post‐synthesis treatment. To demonstrate the generality of the proposed strategy, a nearly identical post‐synthesis “water treatment” method is successfully used to prepare mesoporous monometallic (e.g., manganese oxide (MnO₂)) and bimetallic oxide (e.g., CuCo₂O₄ and MnCo₂O₄) nanospheres assembled of nanosheets or nanoplates with highly enhanced textural characteristics from the corresponding monometallic and bimetallic glycerate nanospheres, respectively. When evaluated as molybdenum (Mo) adsorbents for potential use in molybdenum‐99/technetium‐99m (⁹⁹Mo/^99mTc) generators, the treated mesoporous Al₂O₃ nanospheres display higher molybdenum adsorption performance than non‐treated Al₂O₃ nanospheres and commercial Al₂O₃, thereby suggesting the effectiveness of the proposed strategy for improving the functional performance of oxide materials. It is expected that the proposed method can be utilized to prepare other mesoporous metal oxides with enhanced textural characteristics and functional performance.     

Prediction of geometric uncertainty effects on Fluid Dynamics by Polynomial Chaos and Fictitious Domain method

In this paper the Tensorial-expanded Chaos Collocation method has been used to solve Fluid Dynamic problems with geometric uncertainties. The main advantage of the Tensorial-expanded Chaos Collocation method is its non-intrusive formulation, so existing deterministic solvers can be used. A Least-Squares Spectral Element Method has been employed for the analysis of the deterministic differential problems obtained by Tensorial-expanded Chaos Collocation. This algorithm exploits a Fictitious Domain approach, so it is particularly suitable to solve differential problems defined on stochastic domains. The great capabilities of the Tensorial-expanded Chaos Collocation method combined to the Fictitious Domain-Least-Squares Spectral Element Method are demonstrated by numerical experiments.     

Discrete time sliding mode control of robotic manipulators: Development and experimental validation

This paper presents a robust discrete-time sliding mode control coupled with an uncertainty estimator designed for planar robotic manipulators. Experimental evidence shows satisfactory trajectory tracking performances and noticeable robustness in the presence of model inaccuracies, disturbances and payload perturbations. Ultimate boundedness of the tracking errors is proved, as well as boundedness of the estimation error with arbitrary precision.