Soybean protein-based microparticles for oral delivery of probiotics with improved stability during storage and gut resistance.

The present work describes the encapsulation of probiotics using a by-product as wall material and a process feasible to be scaled-up: coacervation of soybean protein concentrate (SPC) by using calcium salts and spray-drying. SPC was extracted from soybean flour, produced during the processing of soybean milk, by alkaline extraction following isoelectric precipitation. Two probiotic strains were selected for encapsulation (Lactobacillus plantarum CECT 220 and Lactobacillus casei CECT 475) in order to evaluate the ability of SPC to encapsulate and protect bacteria from stress conditions. The viability of these encapsulated strains under in vitro gastrointestinal conditions and shelf-life during storage were compared with the most common forms commercialized nowadays. Results show that SPC is a feasible material for the development of probiotic microparticles with adequate physicochemical properties and enhanced significantly both probiotic viability and tolerance against simulated gastrointestinal fluids when compared to current available commercial forms.

Short bent-core molecules: X-ray, polarization, dielectricity, texture and electro-optics investigations.

Bent-core liquid crystals based on 1,2,4-oxadiazole as a central unit have been the first mesogens to exhibit a ferroelectric response in the nematic phase. This behavior has been widely recognized as due to the presence of smectic-like polar cybotactic clusters permeating the nematic phase. Unfortunately, these compounds exhibited rather high melting points, about 120 °C, due to the presence of four benzene rings in the molecules. Here we describe the synthesis and physical characterization of a new series of BC mesogens, featuring the same bent core as the previous compounds but shorter outer substituents. By keeping only two benzene rings, we were able to lower the melting points to about 70 °C. However, while X-ray diffraction and dielectric spectroscopy measurements confirm the cybotactic nature of the nematic phase of these compounds, polarization and electro-optical measurements ascribe their polar response to flexoelectricity rather than to spontaneous polarization. Finally, texture investigation suggests the biaxiality of the nematic phase, which is indicated also by conoscopic measurements. These results are important for recognizing size and rigidity limitations in designing bent-core liquid crystal molecules suitable for applications.

Technological quality of dough and breads from commercial algarroba-wheat flour blends.

Algarroba flour is used to supplement lysine-limiting systems such as wheat flour due to its amino acidic composition. The effects of adding up to 30% of this flour to wheat flour (W-A30) on dough characteristics and breadmaking performance were studied. Dough rheology was tested by farinograph, oscillatory rheometry and texture profile analyses. Molecular mobility was evaluated by nuclear magnetic resonance, and thermal properties were analyzed by differential scanning calorimetry and viscoamylograph studies. Besides, different bread quality parameters were evaluated. Incorporation of algarroba flour resulted into increase in water absorption, development time and degree of softening, and decrease in stability of wheat flour, leading to softer, less adhesive and elastic dough, although at intermediate replacement levels cohesiveness improved. At the molecular level, a reduction of water activity and limited proton motion were observed in W-A30 samples, suggesting that protons were highly bound to the dough matrix. Dough samples with algarroba flour showed lower G' and G″ values than the control, although with the formation of a more elastic structure for W-A30. In addition, algarroba flour produced a protective effect on starch granule disruption and interfered with amylose-amylose association during cooling. The specific volume of breads decreased with the increase in algarroba level, W-A30 reaching the highest decrease (15%). Bread crumbs with algarroba flour exhibited higher values of hardness and resilience. The use of algarroba flour resulted in lower quality when compared to the control. However, algarroba flour at 20% level can be added to wheat flour to obtain bakery products of similar technological quality and with improved nutritional components.

Dynamical focusing by bent, asymmetrically cut perfect crystals in Laue geometry.

A semi-analytical approach based on the influence functions of a point source located on the crystal surface has been adopted to show that the focusing ability of cylindrically bent Laue crystals may be strongly enhanced by replacing symmetrically cut crystals with asymmetrically cut crystals. This approach is generally applicable to any distance between the X-ray source and the focusing bent crystal. A mathematically straightforward method to simplify the derivation of the already known expression of the influence functions in the case of deformed crystals with a constant strain gradient (e.g. cylindrically bent crystals) is also presented.

Chronic effects of simultaneous electromyostimulation and vibration on leg blood flow in spinal cord injury.

STUDY DESIGN: Randomized two-group parallel. OBJECTIVES: The objective of this study was to analyze the adaptations on the popliteal artery (mean blood velocity (MBV), peak blood velocity (PBV), arterial resting diameter (RD) and blood flow (BF)) induced by 12 weeks of simultaneous application of whole-body vibration and electromyostimulation (WBV+ES) in patients with spinal cord injury (SCI). Secondarily, the musculoskeletal effects of this therapy on the gastrocnemius muscle thickness (MT) and femoral neck bone mineral density (BMD) were analyzed. SETTING: Valladolid, Spain. METHODS: Seventeen SCI patients (American Spinal Injury Association (ASIA) A or B) were randomly assigned to the experimental group (EG=9) or the control group (CG=8). Each subject was assessed in four different occasions: at baseline, after 6 weeks (Post-6) and 12 weeks of the treatment (Post-12) and 8 weeks after the end of the treatment (Post-20). Subjects in the EG performed 30 10-min sessions of WBV+ES during 12 weeks. RESULTS: In the EG, RD increased compared with the baseline value at Post-6 (9.5%, P<0.01), Post-12 (19.0%, P<0.001) and Post-20 (16.7%, P<0.001). Similarly, in the EG, BF increased compared with the baseline value and with CG only at Post-12 ((33.9%, P<0.01) and (72.5%, P<0.05), respectively). Similarly, WBV+ES increased the MT of the gastrocnemius. BMD of both hips remained invariable during the study. CG showed no change at any point. CONCLUSIONS: WBV+ES improved popliteal artery BF, RD and MT after 12 weeks in SCI patients. This increase in RD remained above baseline after 8 weeks. The combination of WBV and ES could be considered a promising alternative to reverse the musculoskeletal atrophy and improve peripheral vascular properties in SCI patients.

Acute effects of simultaneous electromyostimulation and vibration on leg blood flow in spinal cord injury.

STUDY DESIGN: Randomized crossover. OBJECTIVES: To analyze the acute effects of isolated and simultaneous application of whole-body vibration (WBV) and electromyostimulation (ES) on popliteal artery blood velocity (BV) and skin temperature (ST) of the calf in subjects with spinal cord injury (SCI). SETTING: Valladolid, Spain. METHODS: Ten subjects with SCI were assessed in five different sessions. After a familiarization session, four interventions were applied in random order; WBV, ES, simultaneous WBV and ES (WBV+ES), and 30 s of WBV followed by 30 s of ES (WBV30/ES30). Each intervention consisted of 10 sets × 1 min ON+1 min OFF. Subjects were seated on their own wheelchairs with their feet on the vibration platform (10 Hz, 5 mm peak-to-peak), and ES was applied on the gastrocnemius muscle of both legs (8 Hz, 400 µs). RESULTS: The simultaneous application (WBV+ES) produced the greatest increase in mean BV (MBV; 36% and 42%, respectively) and peak BV (PBV; 30% and 36%, respectively) during the intervention. This intervention produced the greatest mean increases in MBV (21%) and PBV (19%) during the recovery period. Last, this intervention produced the highest increase in ST during the intervention (2.1 °C). CONCLUSION: The simultaneous application of WBV+ES seems to produce a greater increase in MBV and PBV of the popliteal artery and ST of the calf than the isolated (WBV or ES) or consecutive application of both stimuli (WBV30/ES30). This study provides an efficient therapeutic methodology to improve peripheral arterial properties, which is pivotal in SCI patient's rehabilitation.

Invivo absorption behaviour of theophylline from starch-methyl methacrylate matrix tablets in beagle dogs.

This study evaluates in vivo the drug absorption profiles from potato starch-methyl methacrylate matrices(*) using theophylline as a model drug. Healthy beagle dogs under fasting conditions were used for in vivo studies and plasma samples were analyzed by a fluorescence polarization immunoassay analysis (FPIA method). Non-compartmental and compartmental (population approach) analysis was performed to determine the pharmacokinetic parameters. The principle of superposition was applied to predict multiple dose plasma concentrations from experimental single dose data. An in vitro-in vivo correlation (IVIVC) was also assessed. The sustained absorption kinetics of theophylline from these formulations was demonstrated by comparison with two commercially available oral sustained-release theophylline products (Theo-Dur(®) and Theolair(®)). A one-compartment model with first order kinetics without lag-time best describes the absorption/disposition of theophylline from the formulations. Results revealed a theophylline absorption rate in the order FD-HSMMA≥Theo-Dur(®)≥OD-CSMMA>Theolair(®)≥FD-CSMMA. On the basis of simulated plasma theophylline levels, a twice daily dosage (every 12h) with the FD-CSMMA tablets should be recommended. A Level C IVIVC was found between the in vitrot50% and the in vivo AUC/D, although further optimization of the in vitro dissolution test would be needed to adequately correlate with in vivo data.

A track length estimator method for dose calculations in low-energy X-ray irradiations: implementation, properties and performance.

The track length estimator (TLE) method, an "on-the-fly" fluence tally in Monte Carlo (MC) simulations, recently implemented in GATE 6.2, is known as a powerful tool to accelerate dose calculations in the domain of low-energy X-ray irradiations using the kerma approximation. Overall efficiency gains of the TLE with respect to analogous MC were reported in the literature for regions of interest in various applications (photon beam radiation therapy, X-ray imaging). The behaviour of the TLE method in terms of statistical properties, dose deposition patterns, and computational efficiency compared to analogous MC simulations was investigated. The statistical properties of the dose deposition were first assessed. Derivations of the variance reduction factor of TLE versus analogous MC were carried out, starting from the expression of the dose estimate variance in the TLE and analogous MC schemes. Two test cases were chosen to benchmark the TLE performance in comparison with analogous MC: (i) a small animal irradiation under stereotactic synchrotron radiation therapy conditions and (ii) the irradiation of a human pelvis during a cone beam computed tomography acquisition. Dose distribution patterns and efficiency gain maps were analysed. The efficiency gain exhibits strong variations within a given irradiation case, depending on the geometrical (voxel size, ballistics) and physical (material and beam properties) parameters on the voxel scale. Typical values lie between 10 and 10(3), with lower levels in dense regions (bone) outside the irradiated channels (scattered dose only), and higher levels in soft tissues directly exposed to the beams.

In vitro release testing of matrices based on starch-methyl methacrylate copolymers: effect of tablet crushing force, dissolution medium pH and stirring rate.

Direct-compressed matrix tablets were obtained from a variety of potato starch-methyl methacrylate copolymers(1) as sustained-release agents, using anhydrous theophylline as a model drug. The aim of this work was to investigate the influence of the copolymer type, the tablet crushing force and dissolution variables such as the pH of the dissolution medium and the agitation intensity on the in vitro drug release behaviour of such matrices. Commercial sustained-release theophylline products (Theo-Dur(®) 100mg, Theolair(®) 175 mg) were used as standards. Test formulations were compacted into tablets at three different crushing force ranges (70-80, 90-100 and 110-120 N) to examine the effect of this factor on the porous network and drug release kinetics. In vitro release experiments were conducted in a pH-changing medium (1.2-7.5) with basket rotation speeds in the range 25-100 r.p.m. to simulate the physiological conditions of the gastrointestinal tract. The release rate of theophylline was practically not affected by pH in the case of Theo-Dur(®) and HSMMA matrices. In contrast, Theolair(®) and CSMMA tablets demonstrated a biphasic drug release pattern, which appeared to be sensitive to the pH of the dissolution medium. An increase in the crushing force of the copolymer matrices was accompanied by a reduction of the matrix porosity, although the porous network depends markedly on the type of copolymer, having a strong influence on the drug release kinetics. Mathematical modelling of release data shows a Fickian diffusion or anomalous transport mechanism. Based on the similarity factor f2, FD-HSMMA, OD-CSMMA and FD-CSMMA at 90-100 N were selected for agitation studies. In general, all formulations showed an agitation speed-dependent release, with Theo-Dur(®) and FD-CSMMA matrices being the less susceptible to this factor.

Spatially-resolved in-situ structural study of organic electronic devices with nanoscale resolution: the plasmonic photovoltaic case study.

A novel high spatial resolution synchrotron X-ray diffraction stratigraphy technique has been applied in-situ to an integrated plasmonic nanoparticle-based organic photovoltaic device. This original approach allows for the disclosure of structure-property relations linking large scale organic devices to length scales of local nano/hetero structures and interfaces between the different components.

Where do we stand with IPF treatment?

Despite receiving 'weak no' recommendations in the updated guidelines on treating patients with Idiopathic Pulmonary Fibrosis (IPF), two key treatment options are pirfenidone and N-acetylcysteine (NAC), and both are used in clinical practice. The efficacy of pirfenidone is supported by a number of Phase III trials as well as a Cochrane meta-analysis. Tolerability data are also provided by clinical trials and a long-term extension phase of these studies. Pirfenidone is approved in Europe for the treatment of patients with mild-to-moderate IPF. NAC-based therapy has no such approval, but is commonly used to treat patients. A Phase III trial suggested some benefit of the NAC, prednisone and azathioprine regimen for IPF patients, but the study had many limitations. A further study to investigate this regimen, compared with a placebo alone arm, was recently stopped due to increased mortality in the triple-therapy arm. Discussion of these data and recent findings highlight the importance of a further update to the existing guidelines, so that IPF specialists can provide the most up-to-date advice and treatment to patients in clinical practice.

Muscular adaptations after two different volumes of blood flow-restricted training.

This study aimed to gain an insight into the adaptations of muscle strength and skeletal muscle thickness after two different volumes of blood flow restriction training (BFRT), and compare them with high-intensity training. The sample was divided into four groups: low-volume, low-intensity BFRT (BFRT LV); high-volume, low-intensity BFRT (BFRT HV); traditional high-intensity resistance training (HIT); and a control group, which maintained their routine activities (CON). Leg extension one repetition maximum (1RM), isokinetic peak knee extension, and flexion torques at 60°/s and 180°/s as well as muscle thickness of the rectus femoris (RF) and vastus lateralis (VL) were assessed at baseline and after 5 weeks of training BFRT LV (7.03%, P < 0.05), BFRT HV (6.24%, P < 0.05) and HIT (18.86%, P < 0.001) groups increased 1RM performance, while no changes were observed in the CON group. Muscle thickness of the RF and VL was increased irrespective of the training group (7.5%, P < 0.001; and 9.9%, P < 0.001, respectively). We conclude that doubling the exercise volume with BFRT causes no further benefit with muscular size or strength. Although similar increases in muscle thickness were observed between training groups, HIT increased 1RM performance to a greater extent compared to either volume of BFRT.

Bent perfect crystals as X-ray focusing polychromators in symmetric Laue geometry.

The focusing properties of cylindrically bent crystals in symmetric Laue geometry are discussed using the formalism of Fresnel diffraction and the analytical solution of the Takagi-Taupin equations for a point source on the entrance surface. The existence of a focal shift in the dynamical focusing effect is pointed out and discussed. The present theoretical framework is applied to experiments performed at the energy-dispersive X-ray absorption spectroscopy beamline of the European Synchrotron Radiation Facility concerning the position and the size of the focal spot obtained from a polychromatic source at a large distance from the bent crystal.

Compaction properties, drug release kinetics and fronts movement studies of matrices combining mixtures of swellable and inert polymers. III: effect of polymer substitution type.

Theophylline radial release from cellulose derivatives with different substitution type (HPMC K4M, HPC H, MC A4M) matrix tablets has been modulated by the introduction of a new inert polymeric excipient, at different proportions (75, 50, 25%). The new polymer was hydroxypropylcellulose-methyl methacrylate (HCMMA), which was dried either in a vacuum oven (OD-HCMMA) or freeze-dried (FD-HCMMA). MC A4M and its mixtures presented the best compaction properties results, especially mixed with FD-HCMMA, according to 100% mixtures. Only high levels of HCMMA (75%) in the matrices showed interesting differences to drug release modulation. Also, at this proportion (75:25), the HPC H mixtures presented the highest differences in relation with OD or FD HCMMA respect to the other cellulose polymers. HPMC K4M and HPC H mixtures showed a combination of diffusion and erosion release mechanisms. The last one was nearly negligible in MC A4M mixtures, according with its highest diffusion rate constant values, and the absence of hydroxypropyl substituents. Only HPMC K4M mixtures presented a diffusion front that moves outwards, while HPC H and MC A4M moves inwards. The modulation of theophylline radial release was obtained using a high percentage of HCMMA, and the use of two cellulosic ethers, one of them with just one type of substituent (MC A4M or HPC H) and the other with two types of substituent (HPMC K4M). Another possibility is changing the HCMMA copolymer (OD or FD) in the 75/25 mixture with HPC.

Graft copolymers of ethyl methacrylate on waxy maize starch derivatives as novel excipients for matrix tablets: drug release and fronts movement kinetics.

A previous paper deals with the physicochemical and technological characterization of novel graft copolymers of ethyl methacrylate (EMA) on waxy maize starch (MS) and hydroxypropylstarch (MHS). The results obtained suggested the potential application of these copolymers as excipients for compressed non-disintegrating matrix tablets. Therefore, the purpose of the present study was to investigate the mechanism governing drug release from matrix systems prepared with the new copolymers and anhydrous theophylline or diltiazem HCl as model drugs with different solubility. The influence of the carbohydrate nature, drying procedure and initial pore network on drug release kinetics was also evaluated. Drug release experiments were performed from free tablets. Radial drug release and fronts movement kinetics were also analysed, and several mathematical models were employed to ascertain the drug release mechanisms. The drug release markedly depends on the drug solubility and the carbohydrate nature but is practically not affected by the drying process and the initial matrix porosity. A faster drug release is observed for matrices containing diltiazem HCl compared with those containing anhydrous theophylline, in accordance with the higher drug solubility and the higher friability of diltiazem matrices. In fact, although diffusion is the prevailing drug release mechanism for all matrices, the erosion mechanism seems to have some contribution in several formulations containing diltiazem. A reduction in the surface exposed to the dissolution medium (radial release studies) leads to a decrease in the drug release rate, but the release mechanism is not essentially modified. The nearly constant erosion front movement confirms the behaviour of these systems as inert matrices where the drugs are released mainly by diffusion through the porous structure.

[Employment of disabled people regarding Italian Law "68/99": Florence's ASL N. 10 experience]. / Inserimento lavorativo dei soggetti disabili ai sensi della legge 68/99: l'esperienza della ASL10 di Firenze.

The reform of mandatory employment in Italy, performed by the national Law 68/99, represented a crucial step for the assertion of the right to work for disabled people. The aim of our experience is to obtain information about health and safety conditions of disabled people employed in targeted workplaces and about the issues for that workers keep or lose their job, possibly in order to take actions on workplaces and to improve job conditions for all other workers also. In this paper we used data regarding targeted employments of disabled people, collected during the year 2008 in the Province of Florence.

Compaction properties, drug release kinetics and fronts movement studies from matrices combining mixtures of swellable and inert polymers. II. Effect of HPMC with different degrees of methoxy/hydroxypropyl substitution.

The aim of this paper is the modification of the release behaviour of hydrophilic HPMC-based matrices of different substitution degree (E4M, F4M, K4M) by the introduction of a new inert polymeric excipient hydroxypropylcellulose-methyl methacrylate (HCMMA) at different proportions (75:25, 50:50 and 25:75). The product (HCMMA) was dried either in a vacuum oven--OD copolymers--or freeze-dried-FD copolymers. HPMC E4M formulations showed the worst compaction properties. All mixtures presented a percentage of theophylline release between 47% and 32% at 1440 min. The drying methods employed had only influence over the drug release in E4M and K4M formulations, at higher proportions of HCMMA, showing the highest release the mixtures containing OD-HCMMA. Combinations of diffusion and erosion release mechanisms were found to matrix tablets. All mixtures with F4M did not modify relaxation rate constant values of Peppas and Shalin equation (k(r)) respect to F4M 100%. However, all mixtures with K4M showed the highest k(r) values, which decreased when HCMMA proportion decreased. Only K4M mixtures showed a different diffusion front movement than the other mixtures. The modulation of theophylline monoaxial release was obtained using a high percentage of HCMMA, and HPMCs with a substantial difference of hydroxypropyl groups (F4M and K4M or E4M).

Pressure dependence of the large-scale structure of water.

We report on small-angle x-ray scattering measurements on liquid water aimed at characterizing the pressure evolution of its large-scale structure. Diffraction profiles have been fitted assuming a Lorentzian dependence on the exchanged momentum. As a result, we observe an anomalous behavior of the diffracted intensity that tends to disappear, increasing either the pressure or the temperature. This effect is discussed in detail and imputed to the ability of hydrostatic pressure to weaken hydrogen bonds.

Simulation of dose deposition in stereotactic synchrotron radiation therapy: a fast approach combining Monte Carlo and deterministic algorithms.

A hybrid approach, combining deterministic and Monte Carlo (MC) calculations, is proposed to compute the distribution of dose deposited during stereotactic synchrotron radiation therapy treatment. The proposed approach divides the computation into two parts: (i) the dose deposited by primary radiation (coming directly from the incident x-ray beam) is calculated in a deterministic way using ray casting techniques and energy-absorption coefficient tables and (ii) the dose deposited by secondary radiation (Rayleigh and Compton scattering, fluorescence) is computed using a hybrid algorithm combining MC and deterministic calculations. In the MC part, a small number of particle histories are simulated. Every time a scattering or fluorescence event takes place, a splitting mechanism is applied, so that multiple secondary photons are generated with a reduced weight. The secondary events are further processed in a deterministic way, using ray casting techniques. The whole simulation, carried out within the framework of the Monte Carlo code Geant4, is shown to converge towards the same results as the full MC simulation. The speed of convergence is found to depend notably on the splitting multiplicity, which can easily be optimized. To assess the performance of the proposed algorithm, we compare it to state-of-the-art MC simulations, accelerated by the track length estimator technique (TLE), considering a clinically realistic test case. It is found that the hybrid approach is significantly faster than the MC/TLE method. The gain in speed in a test case was about 25 for a constant precision. Therefore, this method appears to be suitable for treatment planning applications.

Graft copolymers of ethyl methacrylate on waxy maize starch derivatives as novel excipients for matrix tablets: physicochemical and technological characterisation.

Nowadays, graft copolymers are being used as an interesting option when developing a direct compression excipient for controlled release matrix tablets. New graft copolymers of ethyl methacrylate (EMA) on waxy maize starch (MS) and hydroxypropylstarch (MHS) were synthesised by free radical polymerization and alternatively dried in a vacuum oven (OD) or freeze-dried (FD). This paper evaluates the performance of these new macromolecules and discusses the effect of the carbohydrate nature and drying process on their physicochemical and technological properties. Grafting of EMA on the carbohydrate backbone was confirmed by IR and NMR spectroscopy, and the grafting yields revealed that graft copolymers present mainly a hydrophobic character. The graft copolymerization also leads to more amorphous materials with larger particle size and lower apparent density and water content than carbohydrates (MS, MHS). All the products show a lack of flow, except MHSEMA derivatives. MSEMA copolymers underwent much plastic flow and less elastic recovery than MHSEMA copolymers. Concerning the effect of drying method, FD derivatives were characterised by higher plastic deformation and less elasticity than OD derivatives. Tablets obtained from graft copolymers showed higher crushing strength and disintegration time than tablets obtained from raw starches. This behaviour suggests that these copolymers could be used as excipients in matrix tablets obtained by direct compression and with a potential use in controlled release.