High salt intake during puberty leads to cardiac remodelling and baroreflex impairment in lean and obese male Wistar rats.

Modern lifestyle increases the prevalence of obesity and its co-morbidities in the young population. High-salt (HS) diets are associated with hypertension and cardiac remodelling. The present study evaluated the potential effects of cardiometabolic programming induced by HS intake during puberty in lean and obese rats. Additionally, we investigated whether HS could exacerbate the impairment of cardiovascular parameters in adult life due to postnatal early overnutrition (PO). At postnatal day 3 (PN3), twenty-four litters of Wistar rats were divided into two groups: normal litter (NL, nine pups/dam) and small litter (SL, three pups/dam) throughout the lactation period; weaning was at PN21. At PN30, the pups were subdivided into two more groups: NL plus HS (NLHS) and SL plus HS (SLHS). HS intake was from PN30 until PN60. Cardiovascular parameters were evaluated at PN120. SL rats became overweight at adulthood due to persistent hyperphagia; however, HS exposure during puberty reduced the weight gain and food intake of NLHS and SLHS. Both HS and obesity raised the blood pressure, impaired baro- and chemoreflex sensitivity and induced cardiac remodelling but no worsening was observed in the association of these factors, except a little reduction in the angiotensin type-2 receptor in the hearts from SLHS animals. Our results suggest that the response of newborn offspring to PO and juveniles to a HS diet leads to significant changes in cardiovascular parameters in adult rats. This damage may be accompanied by impairment of both angiotensin signalling and antioxidant defence in the heart.

Alpha-tocopheryl succinate improves encapsulation, pH-sensitivity, antitumor activity and reduces toxicity of doxorubicin-loaded liposomes.

Doxorubicin (DOX) plays an important role in cancer treatment; however, high cardiotoxicity and low penetration in solid tumors are the main limitations of its use. Liposomal formulations have been developed to attenuate the DOX toxicity, but the technological enhancement of the liposomal formulation as well as the addition of another agent with antitumor properties, like alpha-tocopheryl succinate (TS), a semi-synthetic analog of vitamin E, could certainly bring benefits. Thus, in this study, it was proposed the development of liposomes composed of DOX and TS (pHSL-TS-DOX). A new DOX encapsulation method, without using the classic ammonium sulfate gradient with high encapsulation percentage was developed. Analysis of Small Angle X-ray Scattering (SAXS) and release study proved the pH-sensitivity of the developed formulation. It was observed stabilization of tumor growth using pHSL-TS-DOX when compared to free DOX. The toxicity tests showed the safety of this formulation since it allowed body weight initial recovery after the treatment and harmless to heart and liver, main target organs of DOX toxicity. The developed formulation also avoided the occurrence of myelosuppression, a typical adverse effect of DOX. Therefore, pHSL-TS-DOX is a promising alternative for the treatment of breast cancer since it has adequate antitumor activity and a safe toxicity profile.

Modified binodal model describes phase separation in aqueous two-phase systems in terms of the effects of phase-forming components on the solvent features of water.

The binodal model pioneered by Guan et al. [Y. Guan, T. H. Lilley, T. E. Treffry, J. Chem. Soc. Faraday Trans., 89 (1993) 4283-4298] remains the most successful in regard to the quantitative description of phase diagrams among various theoretical models proposed to describe phase separation in aqueous mixtures of polymers. This is a semi-empirical model based on the assumption that any point on the binodal line may be viewed as a saturated solution of the phase-forming compound-1 in the solution of the phase-forming compound-2. Although this model is originally based on the excluded volume concept, we suggest that the solubility of the compound-1 in solutions of compound-2 may depend on the solvent properties of water in solutions of compound-2. The binodal model described in these terms was very successfully applied to the phase diagrams of aqueous two-phase systems formed by different pairs of polymers (dextran, Ficoll, poly(ethylene glycol)-8000, and Ucon). Phase diagram of a new aqueous two-phase system formed by trimethylamine N-oxide (TMAO) and polypopylene glycol-400 and previously reported phase diagram for system formed by TMAO and poly(ethylene glycol)-600 were also described by this model quite well. It was found that the modified binodal model is also applicable to single polymer-salt and polymer-ionic liquid aqueous two-phase systems. The most important conclusion of our study is that the effects of different compounds (polymers, salts, ionic liquids) on the solvent features of water in their aqueous solutions cause changes in the water structure, resulting in phase separation in the mixtures of these compounds.

Role of solvent properties of water in crowding effects induced by macromolecular agents and osmolytes.

Solvent properties of water in aqueous solutions of polyethylene glycols of various molecular weights, l-proline, betaine, and a series of chlorides of varied concentrations are assayed using three solvatochromic dyes. The properties include solvent dipolarity/polarizability, hydrogen bond donor acidity, and hydrogen bond acceptor basicity. These properties are also evaluated in mixtures of two polymers, polymer and osmolyte, and two osmolytes. It is shown that linear combinations of solvent dipolarity/polarizability and hydrogen bond donor acidity assayed in individual solutions of crowders strongly correlate with the effects of the crowders on the stability of various proteins and nucleic acids reported in the literature. The solvent properties of water in aqueous mixtures of two macromolecular crowders, two osmolytes, or mixtures of an osmolyte and a macromolecular crowder vary differently for various solvent properties. The overall effects of the two components in the mixture on a given solvent property of water may be additive, reduced or enhanced depending on the particular composition of the mixture. It is hypothesized that changes in the solvent properties of water are related to changes in the water hydrogen-bonding structuring. It is suggested that the observed crowder-induced changes in the solvent properties of water should be taken into account in theoretical considerations of crowding effects in biological systems.

Epicardial fat thickness correlates with P-wave duration, left atrial size and decreased left ventricular systolic function in morbid obesity.

BACKGROUND AND AIM: Epicardial fat (EF) is increased in obesity and has important interactions with atrial and ventricular myocardium. Most of the evidence in this scenario can be confused by the presence of comorbidities such as hypertension, diabetes and dyslipidemia, which are very common in this population. The influence of EF on atrial remodeling and cardiac function demands further investigation on morbidly obese without these comorbidities. METHODS AND RESULTS: We prospectively recruited 20 metabolically healthy morbidly obese and 20 normo-weights controls. The maximum P-wave duration (PWD) was analyzed by 12-lead electrocardiogram. Left atrial diameter (LAD), left ventricular ejection fraction (LVEF) and EF thickness (EFT) were evaluated by two-dimensional echocardiography. The mean of maximum PWD and LAD were significantly larger in the obese group as compared to the control group: 109.55 ± 11.52 ms × 89.38 ± 11.19 ms and 36.12 ± 3.46 mm × 31.45 ± 2.64 mm, (p < 0.0001). The mean LVEF was lower in the obese group: 63.15 ± 4.25% × 66.17 ± 3.37% (p < 0.017). The mean EFT was higher in the obese group: 7.72 ± 1.60 mm × 3.10 ± 0.85 mm (p < 0.0001). A positive correlation was found between EFT and PWD (r = 0.70; p = 0.001) and LAD (r = 0.667; p = 0.001). An inverse correlation was found between EFT and LVEF (r = -0.523; p = 0.001). In a multiple multivariate regression analysis the EFT remains correlated with LAD and LVEF. CONCLUSIONS: In a select group of morbidly obese, the excess of EF had a significant impact on atrial remodeling and cardiac function.

Skin hyperpigmentation following intravenous polymyxin B treatment associated with melanocyte activation and inflammatory process.

What is known and objective Polymyxins were widely used until the 1960s; however, they fell into disfavour owing to their toxicity. The subsequent growth of infections caused by multidrug-resistant Gram-negative bacteria has led to renewed use of this class of antimicrobials in clinical practice. Acquired skin hyperpigmentation (SH) following intravenous polymyxin B treatment has been previously reported, but little is known about its pathogenesis, clinical course and treatment. To improve understanding of these issues, we conducted a prospective study of adult patients receiving intravenous polymyxin B treatment. Methods Patients receiving intravenous polymyxin B treatment were followed throughout the course of treatment. Clinical, dermatoscopic, histologic and immunohistochemical skin properties of patients who presented with SH were studied. Results and discussion Skin hyperpigmentation was noted in 8% of patients (n=20/249); however, clinical, dermatoscopic, histologic and immunohistochemical examinations were performed only in three patients for whom the consent of relatives was obtained. Histologic and immunohistochemical findings showed an abundant melanocyte-pigmented dendritic network. Langerhans cells' hyperplasia and dermal IL-6 overexpression were also found, presumably for an inflammatory process due to polymyxin B use. As polymyxin B causes the release of histamine, which is known for its melanogenic effect, it is possible that skin darkening is associated with this inflammatory mediator. What is new These clinical and dermatoscopic findings contribute to a better understanding of how the pigmentary reaction manifests following intravenous polymyxin B treatment. Conclusion We concluded that hyperpigmentation due to intravenous polymyxin B treatment is associated with an inflammatory process and subsequent melanocyte activation. Although the pigmentary disorder neither influences the outcome of the therapy nor warrants discontinuation of treatment, it nevertheless considerably affects the patient's quality of life.

Effects of the Hofmeister series of sodium salts on the solvent properties of water.

The solvent features of water (solvent dipolarity/polarizability, π*, hydrogen bond donor acidity, α, and hydrogen bond acceptor basicity, ß) were examined in aqueous solutions of Na2SO4, NaF, CH3COONa, NaCl, NaBr, NaI, and NaClO4 at concentrations of each salt from 0 to 1.0 M (up to 2.0 M for NaClO4). The solvent features of water in solutions of different concentrations for each salt were found to be linearly related as π* = z + aα + bß. The coefficients of this relationship were suggested to represent the signature of the salt effect on the solvent features of water. The normalized distances for each salt were calculated using glucose as a reference compound. These distances may be used as the relative measures of the salt-water interactions. It is demonstrated that the distances for all salts examined are interrelated with structural water entropies and static polarizabilities of anions. It is shown that the distance may be used as a measure of the relative effects of salts on precipitation of ferric oxide, excessive chemical potential of propanol in salt solutions, surface tension, and viscosity. The distance represents the relative measure of the salt effect on the solvent features of water in a salt solution. The examples presented confirm that the approach used does enable us to characterize the differences between the effects of salts in the Hofmeister series on the properties of water.

Responses of polar organic compounds to different ionic environments in aqueous media are interrelated.

Solubilities of 17 polar organic compounds in aqueous solutions of Na2SO4, NaCl, NaClO4, and NaSCN at the salt concentrations of up to 1.0-2.0 M were determined and the Setschenow constant, ksalt, values were estimated. It was found that NaClO4 may display both salting-in and salting-out effects depending on the particular compound structure. The Setschenow constant values for all the polar compounds examined in different salt solutions are found to be interrelated. Similar relationships were observed for partition coefficients of nonionic organic compounds in aqueous polyethylene glycol-sodium sulfate two-phase systems in the presence of different salt additives reported previously [Ferreira et al., J. Chromatogr. A, 2011, 1218, 5031], and for the effects of different salts on optical rotation of amino acids reported by Rossi et al. [J. Phys. Chem. B, 2007, 111, 10510]. In order to explain the observed relationships it is suggested that all the effects observed originate as responses of the compounds to the presence of a given ionic environment and its interaction with the compounds by forming direct or solvent-separated ionic pairs. The response is compound-specific and its strength is determined by the compound structure and the type (and concentration) of ions inducing the response.

Comedolytic effect and reduced skin irritation of a new formulation of all-trans retinoic acid-loaded solid lipid nanoparticles for topical treatment of acne.

Novel drug delivery systems, such as solid lipid nanoparticles (SLN), have been proposed to reduce retinoic acid (RA)-induced skin irritation. However, one question still remains: could it be accomplished without reducing efficacy? To evaluate this question the comedolytic effects and epidermal thickening of RA-loaded SLN were compared to the conventional RA formulations (gel or cream), as well as the potential of these formulations to induce skin irritation. The comedolytic effects and epidermal thickening of these formulations, both containing RA at 0.01 or 0.05%, were investigated in a rhino mouse model, while the studies of RA-induced skin irritation were evaluated through rabbit skin irritation tests and in the rhino mouse model. RA-loaded SLN, as compared to the placebo, produced a comedolytic effect with a significant reduction of the utricle diameter, which proved to be similar to that observed for marketed gels or creams regardless of the RA concentration. RA formulations (SLN or marketed cream) also induced an epidermal proliferation leading to a thickened epidermis in treated animals. In both animals studied (rhino mice and rabbits), the RA-loaded SLN, when compared to conventional formulations, promoted a significant reduction in RA-induced skin irritation (erythema and scaling). Then, RA-loaded SLN represents an interesting alternative to reduce RA-induced skin irritation without reducing efficacy, and constitutes an innovative approach for the topical treatment of acne with RA.

Modal interferometer based on hollow-core photonic crystal fiber for strain and temperature measurement.

In this work, sensitivity to strain and temperature of a sensor relying on modal interferometry in hollow-core photonic crystal fibers is studied. The sensing structure is simply a piece of hollow-core fiber connected in both ends to standard single mode fiber. An interference pattern that is associated to the interference of light that propagates in the hollow core fundamental mode with light that propagates in other modes is observed. The phase of this interference pattern changes with the measurand interaction, which is the basis for considering this structure for sensing. The phase recovery is performed using a white light interferometric technique. Resolutions of +/- 1.4 microepsilon and +/- 0.2 degrees C were achieved for strain and temperature, respectively. It was also found that the fiber structure is not sensitive to curvature.

Wobbles and other kink-breather solutions of the sine-Gordon model.

We study various solutions of the sine-Gordon model in (1+1) dimensions. We use the Hirota method to construct some of them and then show that the wobble, discussed in detail in a recent paper by Kälberman, is one of such solutions. We concentrate our attention on a kink and its bound states with one or two breathers. We study their stability and some aspects of their scattering properties on potential wells and on fixed boundary conditions.

All-fiber Mach-Zehnder curvature sensor based on multimode interference combined with a long-period grating.

A novel Mach-Zehnder interferometer based on a fiber multimode interference structure combined with a long-period fiber grating (LPG) is proposed. The multimode interference is achieved through the use of a MMF section spliced between two single-mode fibers, with a length adjusted to couple a fraction of light into the cladding modes. A LPG placed after the MMF couples light back into the fiber core, completing the Mach-Zehnder interferometer. This novel configuration was demonstrated as a bending sensor.

Absorption-line-locked fiber laser for gas-sensing applications.

An absorption-line-locked fiber laser based on the selection and conversion of a gas absorption line into a highly stable intracavity transmission narrowband filter is demonstrated. The laser has attractive properties for gas-sensing applications due to its frequency stability and multiwavelength selection capability.

Optical flowmeter using a modal interferometer based on a single nonadiabatic fiber taper.

A novel in-fiber modal interferometer is presented that is based on a nonadiabatic biconical fused taper that couples light between the cladding and the core, combined with the Fresnel reflection at the fiber end. It is observed that the returned light from this fiber structure shows a channeled spectrum similar to that of a two-wave Michelson interferometer. The application of this device as a fiber optic flowmeter sensor is demonstrated.

Optical inclinometer based on a single long-period fiber grating combined with a fused taper.

A new concept to measure rotation angles based on a fiber-optic modal Mach-Zehnder interferometer is demonstrated by using a nonadiabatic taper cascaded with a long-period fiber grating. Information about the magnitude of the rotation angle can be obtained from the measurement of the interference pattern visibility, and under certain conditions it is also possible to obtain the sign of the rotation angle from the induced phase variation in the fiber interferometer.

Intensity-referenced and temperature-independent curvature-sensing concept based on chirped fiber Bragg gratings.

An intensity-referenced temperature-independent curvature-measurement technique that uses a smart composite that comprises two chirped fiber Bragg gratings is demonstrated. The two gratings are embedded on opposite sides of the composite laminate and act simultaneously as curvature sensors and as wavelength discriminators, enabling a temperature-independent intensity-based scheme to measure radius of curvature. Also, the system's performance is independent of arbitrary power losses that are induced in the lead fibers to the sensing head. It is demonstrated that the measurement range depends on the relative positions of the chirped fiber Bragg gratings and on their spectral bandwidths. By using two chirped fiber Bragg gratings with bandwidths W1 = 2.8 nm and W2 = 3.7 nm and with central wavelengths at lambda 01 = 1560.3 nm and lambda 02 = 1563.7 nm, we obtained a resolution of 1.6 mm/square root of Hz for the measurement of the radius of curvature (approximately R = 350 mm) over the measurement range 190 mm < R < infinity.

Simultaneous determination of curvature, plane of curvature, and temperature by use of a miniaturized sensing head based on fiber Bragg gratings.

We present what we believe to be a novel miniaturized sensor configuration based on fiber Bragg gratings for simultaneous measurement of curvature and temperature in smart structures and composite materials. Because of the particular geometry of the sensing head, it is possible not only to measure the radius of curvature but also to determine the plane of curvature. We arrange three Bragg gratings in the vertices of the smallest equilateral triangle that can be defined by the cross sections of the fibers. The set is then inserted into a glue-filled capillary stainless-steel tube to provide both suitable protection for the Bragg sensors and rotational symmetry to the sensing head. This tube also ensures isolation from axial strain, allowing for the additional determination of temperature. The proposed sensing head is particularly well suited for applications in smart structures because it can be embedded along any layer of a composite material (including the neutral line) without special concern for the relative orientation of the Bragg gratings and the composite layers. We can also use this sensing configuration to implement more-sophisticated sensors dedicated, for example, to the measurement of multiaxial acceleration or flow and temperature.

Fiber Bragg grating-based self-referencing technique for wavelength-multiplexed intensity sensors.

An amplitude-phase-conversion self-referencing technique for intensity-modulated photonic sensors that uses two different-wavelength fiber Bragg gratings is presented. With this technique, the system response has been demonstrated to be almost unafffected by network power variations as high as 90% of the total power launched by the source. We prove the multiplexing capability of this type of self-referenced fiber sensor by wavelength-division multiplexing two of them in a star network. A tunable fused biconical wavelength-division multiplexer is used for sensor addressing at the detection block, providing both good isolation and low cross-talk values.

Preparação e caracterização de extratos glicólicos enriquecidos em taninos a partir das cascas de Stryphnodendron adstringens (Mart. ) Coville (Barbatimão) / Preparation and characterization of propylene glicol extracts obtained from dried stem barks of Stryphnodendron adstringens (Mart. ) Coville (barbatimão)

Neste estudo, foram preparados e caracterizados extratos glicólicos de cascas de Stryphnodendron adstringens (barbatimão), visando a obtenção de extratos enriquecidos em taninos. Os extratos foram preparados, em triplicata, por meio de maceração estática da droga vegetal pulverizada, seguida de percolação, com diferentes misturas de 90 por cento (PGL90), 80 por cento (PGL80) e 70 por cento (PGL70) de propilenoglicol em água. Os extratos foram recolhidos de forma fracionada. Cada fração obtida foi submetida a análises de pH, densidade, determinação de resíduo seco, e dos teores de taninos e de polifenóis. Os resultados dessas análises demonstraram que o solvente PGL70 extraiu maior quantidade de constituintes químicos da droga vegetal, a partir das primeiras frações. No entanto, as análises revelaram que o solvente PGL80 foi mais seletivo ao extrair, especificamente, os taninos da planta. Os resultados indicaram que a incorporação de 20 por cento de água ao propilenoglicol deve conduzir a extratos mais enriquecidos em taninos, a partir das cascas de barbatimão.

Extracts from dried stem barks of Stryphnodendron adstringens (barbatimão) were prepared with 90 percent, 80 percent and 70 percent of propylene glycol and water (PGL90, PGL80 and PGL70, respectively). The extract was prepared by percolation and collected as fractions of 100mL. The pH, density, dry residue and tannin and polyphenolic contents were determined for each fraction. The results showed that the extraction of chemical compounds was more efficient with PGL70, but PGL80 was more selective for extraction of tannins, the active compounds.

Combined interleukin-12 and topical chemotherapy for established Leishmaniasis drastically reduces tissue parasitism and relapses in susceptible mice.

The efficacy of the association of paromomycin sulfate (PA) with recombinant (r) interleukin (IL)-12 was investigated by topical treatment of BALB/c mice infected with Leishmania major that displayed fully developed cutaneous lesions. Although healing was observed in PA-treated groups, lesions recurred in 100% of these animals 70 days after treatment. In contrast, lesions were absent in a high proportion of PA- and rIL-12-treated mice 120 days after treatment. The PA/rIL-12-treated mice had a switch in cytokine response, from high IL-4 and low interferon (IFN)-gamma levels to low IL-4 and high IFN-gamma levels, and reductions in parasite load, dissemination of parasites, and inflammation. Thus, the association of rIL-12 to topical chemotherapy for leishmaniasis may be an important strategy for increasing cure rates and decreasing the incidence of relapse.