Long-term metabolic correction of Wilson's disease in a murine model by gene therapy.

BACKGROUND & AIMS: Wilson's disease (WD) is an autosomal recessively inherited copper storage disorder due to mutations in the ATP7B gene that causes hepatic and neurologic symptoms. Current treatments are based on lifelong copper chelating drugs and zinc salts, which may cause side effects and do not restore normal copper metabolism. In this work we assessed the efficacy of gene therapy to treat this condition. METHODS: We transduced the liver of the Atp7b(-/-) WD mouse model with an adeno-associated vector serotype 8 (AAV8) encoding the human ATP7B cDNA placed under the control of the liver-specific α1-antitrypsin promoter (AAV8-AAT-ATP7B). After vector administration we carried out periodic evaluation of parameters associated with copper metabolism and disease progression. The animals were sacrificed 6months after treatment to analyze copper storage and hepatic histology. RESULTS: We observed a dose-dependent therapeutic effect of AAV8-AAT-ATP7B manifested by the reduction of serum transaminases and urinary copper excretion, normalization of serum holoceruloplasmin, and restoration of physiological biliary copper excretion in response to copper overload. The liver of treated animals showed normalization of copper content and absence of histological alterations. CONCLUSIONS: Our data demonstrate that AAV8-AAT-ATP7B-mediated gene therapy provides long-term correction of copper metabolism in a clinically relevant animal model of WD providing support for future translational studies.

Reduced-fat bologna sausages with improved lipid fraction.

BACKGROUND: This applied research was done in order to obtain cooked products (bologna sausages) with significantly lower amounts of energy, total fat and saturated fat and higher amounts of ω-3 fatty acids than conventional ones. Two subsequent experiments were performed. RESULTS: Experiment 1 aimed at pork back-fat reduction and enabled sausages to be obtained with 84 g kg⁻¹ fat and 1334 kcal kg⁻¹, without significant negative effects on sensory quality. Carrageenan was used as fat replacer. Experiment 2 aimed at improving the lipid profile of the 'energy-reduced' sausages previously developed, by a partial substitution of the pork back-fat with a linseed oil-in water emulsion (substitution levels: 25-100%). Using the 100% substitution level gave rise to products with 27 g kg⁻¹ α-linolenic acid, and low saturated fat content (13.5 g kg⁻¹), showing good sensory results regarding taste, smell and texture. The use of antioxidant maintained low TBARs (thiobarbituric acid reactive substances) values in all formulations. CONCLUSION: It is possible to obtain cooked meat products (bologna sausages) with low energy, low saturated fat and a high amount of ω-3 fatty acids simultaneously, applying a combination of the use of carrageenan, linseed oil emulsion and increment of water, without significant effects on sensory quality. Functional products, interesting from a nutritional standpoint, were achieved.

Study on the Interaction of Polymeric Chemical Additives with Phase Change Materials in Air Lime Renders.

The interaction of microencapsulated phase change materials (PCMs) with polymeric chemical additives in an air lime binding matrix was studied. These polymer-based additives included an adhesion booster (derived from starch) and a superplasticizer (polycarboxylate ether). Two different PCMs with melting points of 18 °C and 24 °C were assayed. The microcapsules were composed of melamine, with paraffin-based PCM cores. Measurements of zeta potential, particle size distribution, adsorption isotherms, and viscosity analyses were performed to comprehend the behavior of the polymer-based additives within the air lime matrix and their compatibility with PCMs. Zeta potential experiments pointed to the absence of a strong interaction between the lime particles and the microcapsules of PCMs. At the alkaline pH of the lime mortar, the negative charge resulting from the deprotonation of the melamine shell of the microcapsules was shielded by cations, yielding high positive zeta potential values and stable dispersions of lime with PCMs. The polycarboxylate ether demonstrated the ability to counteract the increase in mixing water demand caused by the PCM addition in the lime matrix. The dispersing action of the superplasticizer on the lime particles was seen to exert a collateral dispersion of the PCMs. Conversely, despite the positive values of zeta potential, the addition of the starch-based additive resulted in the formation of large PCM-lime clumps. Air lime renders incorporating 5, 10, and 20% PCMs by weight with various dosages of these chemical additives were experimented with until the optimal formulation for the specific application of the mortars as renderings was achieved. This fine-tuned formulation effectively tackled issues commonly associated with the addition of PCMs to mortars, such as poor adhesion, crack formation, and reduced fluidity.

Pristine Photopolymerizable Gelatin Hydrogels: A Low-Cost and Easily Modifiable Platform for Biomedical Applications.

The study addresses the challenge of temperature sensitivity in pristine gelatin hydrogels, widely used in biomedical applications due to their biocompatibility, low cost, and cell adhesion properties. Traditional gelatin hydrogels dissolve at physiological temperatures, limiting their utility. Here, we introduce a novel method for creating stable hydrogels at 37 °C using pristine gelatin through photopolymerization without requiring chemical modifications. This approach enhances consistency and simplifies production and functionalization of the gelatin with bioactive molecules. The stabilization mechanism involves the partial retention of the triple-helix structure of gelatin below 25 °C, which provides specific crosslinking sites. Upon activation by visible light, ruthenium (Ru) acts as a photosensitizer that generates sulphate radicals from sodium persulphate (SPS), inducing covalent bonding between tyrosine residues and "locking" the triple-helix conformation. The primary focus of this work is the characterization of the mechanical properties, swelling ratio, and biocompatibility of the photopolymerized gelatin hydrogels. Notably, these hydrogels supported better cell viability and elongation in normal human dermal fibroblasts (NHDFs) compared to GelMA, and similar performance was observed for human pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). As a proof of concept for functionalization, gelatin was modified with selenous acid (GelSe), which demonstrated antioxidant and antimicrobial capacities, particularly against E. coli and S. aureus. These results suggest that pristine gelatin hydrogels, enhanced through this new photopolymerization method and functionalized with bioactive molecules, hold potential for advancing regenerative medicine and tissue engineering by providing robust, biocompatible scaffolds for cell culture and therapeutic applications.

Reduction of sodium and increment of calcium and ω-3 polyunsaturated fatty acids in dry fermented sausages: effects on the mineral content, lipid profile and sensory quality.

BACKGROUND: A combined technological approach was applied in the development of healthier dry fermented sausages: a partial substitution of the pork back fat by pre-emulsified linseed oil and a partial replacement of sodium chloride with calcium ascorbate at two different levels, leading to low amounts of salt (14gSalt and 10gSalt, with 14 g and 10 g NaCl per kg of mixture, respectively). RESULTS: The developed products (14gSalt and 10gSalt) showed adequate results for a(w) (0.85 and 0.87) and pH (4.98 and 5.21), and low lipid oxidation values (1.4 × 10(-4) and 1.5 × 10(-5) g malondialdehyde (MDA) kg(-1)). The lipid modification led to a significantly higher supply of ω-3 (23.3 g kg(-1) ) compared to the control (3.2 g kg(-1) ). Simultaneously, reductions of 38% and 50% in sodium content and a calcium supply of 4 and 5.2 g kg(-1) were achieved in the 14gSalt and 10gSalt formulations, respectively, compared to the control products (26 g salt and 0.87 g kg(-1) Ca). Instrumental analysis of colour and texture and sensory studies demonstrated that the organoleptic quality of the new formulations was similar to that of traditional products. CONCLUSIONS: The developed dry fermented sausages showed healthier properties than traditional ones owing to their reduced sodium and higher calcium content and a significant supply of ω-3 fatty acids.

Genotoxicity and Toxicity Assessment of a Formulation Containing Silver Nanoparticles and Kaolin: An In Vivo Integrative Approach.

A new material composed of a kaolin base with silver nanoparticles (AgNPs) attached to its surface was developed, as an alternative to antibiotics used as supplements in animal feed. As part of its safety assessment, an in vivo geno-toxicological evaluation of this material was conducted in rats. First, a preliminary dose finding study was carried out to decide the doses to be tested in the main study: 50, 300 and 2000 mg/kg b.w. For the main study, a combined strategy composed of the MN test (TG 474) and the comet assay (TG 489), integrated in a repeated dose 28-day oral toxicity study (TG 407), was performed. A No Observed Adverse Effect Level (NOAEL) of 2000 mg of the silver-kaolin formulation/kg b.w. by oral route, for 28 days, was determined. The silver-kaolin formulation did not induce micronuclei in bone marrow, or DNA strand breaks (SBs) or alkali labile sites (ALS) in liver, spleen, kidney or duodenum at any dose. The modified Fpg comet assay did not reveal oxidized bases in the same tissues at the dose of 2000 mg/kg b.w. Silver was quantified by ICP-MS in all the target organs, confirming the negative results obtained under these conditions.

Relationship of oxidized low density lipoprotein with lipid profile and oxidative stress markers in healthy young adults: a translational study.

BACKGROUND: Despite oxidized low density lipoprotein (ox-LDL) plays important roles in the pro-inflammatory and atherosclerotic processes, the relationships with metabolic and oxidative stress biomarkers have been only scarcely investigated in young adult people. Thus, the aim of this study was to assess plasma ox-LDL concentrations and the potential association with oxidative stress markers as well as with anthropometric and metabolic features in healthy young adults. METHODS: This study enrolled 160 healthy subjects (92 women/68 men; 23±4 y; 22.0±2.9 kg/m2). Anthropometry, body composition, blood pressure, lifestyle features, biochemical data, and oxidative stress markers were assessed with validated tools. Selenium, copper, and zinc nail concentrations were measured by atomic absorption spectrophotometry. RESULTS: Total cholesterol (TC), LDL-c and uric acid concentrations, TC-to-HDL-c ratio, and glutathione peroxidase (GPx) activity were positive predictors of ox-LDL concentrations, while nail selenium level (NSL) was a negative predictor, independently of gender, age, smoking status, physical activity. Those individuals included in the highest tertile of GPx activity (≥611 nmol/[mL/min]) and of NSL (≥430 ng/g of nail) had higher and lower ox-LDL concentrations, respectively, independently of the same covariates plus truncal fat or body mass index, and total cholesterol or LDL-c concentrations. CONCLUSIONS: Ox-LDL concentrations were significantly associated with lipid biomarkers, GPx activity, uric acid concentration, and NSL, independently of different assayed covariates, in young healthy adults. These findings jointly suggest the early and complex relationship between lipid profile and redox status balance.

Anti-proliferative effect of Melissa officinalis on human colon cancer cell line.

Melissa officinalis L. (Lamiaceae) is consumed as a traditional herbal tea in the Mediterranean region. The cytotoxic effect of the 50% ethanolic and aqueous extract, determined by the MTT and NR assays, was evaluated in vitro on Human Colon Cancer Cell Line (HCT-116), using Triton 10% as positive control. The 50% ethanolic extract showed significant differences after 72 h of treatment, reducing cell proliferation to values close to 40%, even the lowest dose tested (5 µg/ml). In the MTT assay, the same extract caused the lowest cell viability with 13% at a concentration of 1,000 µg/ml after 72 h of treatment, being a value lower than Triton 10%. The antioxidant activity was also confirmed evaluating the capacity of the extracts to scavenge ABTS and DPPH radicals, and IC(50) values were highly correlated with the total phenolic and flavonoid content. Bioassay guided fractionation led to the isolation of an anti-proliferative compound, rosmarinic acid. Its structural elucidation was performed by HPLC/DAD/ESI/MS analysis. High dose of rosmarinic acid (1,000 µg/ml) was clearly cytotoxic against HCT-116 cells, with a significant decrease in cell number since the earliest time point (24 h).

Oral Efficacy of a Diselenide Compound Loaded in Nanostructured Lipid Carriers in a Murine Model of Visceral Leishmaniasis.

Leishmaniasis urgently needs new oral treatments, as it is one of the most important neglected tropical diseases that affects people with poor resources. The drug discovery pipeline for oral administration currently discards entities with poor aqueous solubility and permeability (class IV compounds in the Biopharmaceutical Classification System, BCS) such as the diselenide 2m, a trypanothione reductase (TR) inhibitor. This work was assisted by glyceryl palmitostearate and diethylene glycol monoethyl ether-based nanostructured lipid carriers (NLC) to render 2m bioavailable and effective after its oral administration. The loading of 2m in NLC drastically enhanced its intestinal permeability and provided plasmatic levels higher than its effective concentration (IC50). In L. infantum-infected BALB/c mice, 2m-NLC reduced the parasite burden in the spleen, liver, and bone marrow by at least 95% after 5 doses, demonstrating similar efficacy as intravenous Fungizone. Overall, compound 2m and its formulation merit further investigation as an oral treatment for visceral leishmaniasis.

3,5-Dimethyl-4-isoxazoyl selenocyanate as promising agent for the treatment of Leishmania infantum-infected mice.

Compounds 1 and 2 (selenocyanate and diselenide derivatives, respectively) were evaluated for their potential use in vivo against visceral leishmaniasis (VL). Both entities showed low cytoxicity in vitro in Vero and Caco-2 cell lines. However, the compounds were not suitable for their oral administration, since they exhibited poor values of intestinal permeability in vitro. Microsomal stability assays did not show any metabolite for compound 1 after 120 min, whereas 2 was highly metabolized by the enzyme CYP450. Thus, the in vivo efficacy of compound 1 was assessed in a murine model of L. infantum VL. The daily i.v. administration of 1 mg/kg of compound 1 during 5 consecutive days reduced parasite load in liver, spleen and bone marrow (99.2%, 91.7% and 61.4%, respectively) compared to non-treated mice. To the best of our knowledge, this is the first time that a selenium compound has been tested in vivo against VL. Thus, this work evidences the possible usefulness of selenocyanate derivatives for the treatment of this disease.

Combination of Polymeric Superplasticizers, Water Repellents and Pozzolanic Agents to Improve Air Lime-Based Grouts for Historic Masonry Repair.

This paper presents the experimental procedure to develop air lime-based injection grouts, including polymeric superplasticizers, a water repellent agent and pozzolanic agents as additives. Our research focuses on the development of grouts to improve various characteristics simultaneously by combining different additions and admixtures. Aiming to improve the injectability of the grouts, in this study, different polymeric superplasticizers were added, namely polycarboxylated-ether derivative (PCE), polynaphthalene sulfonate (PNS) and condensate of melamine-formaldehyde sulfonate (SMFC). As a water-repellent agent, sodium oleate was used to reduce the water absorption. The enhancement of the strength and setting time was intended by using microsilica and metakaolin as pozzolanic mineral additions. Compatibility between the different admixtures and action mechanism of the different polymers were studied by means of zeta potential and adsorption isotherms measurements. Diverse grout mixtures were produced and investigated by assessing their injectability, fluidity, stability, compressive strength, hydrophobicity and durability. This research led to several suitable mixtures produced by using more than one component, to enhance efficiency and to provide better performance of grouts. According to the results, the grout composed of air lime, metakaolin, sodium oleate and PCE was found to be the most effective composition, improving the mechanical strength, injectability and hydrophobicity.

Effects of a 6-month dietary-induced weight loss on erythrocyte membrane omega-3 fatty acids and hepatic status of subjects with nonalcoholic fatty liver disease: The Fatty Liver in Obesity study.

BACKGROUND: Omega-3 polyunsaturated fatty acids (PUFAs) have been suggested as important biomolecules in the management of nonalcoholic fatty liver disease (NAFLD). OBJECTIVE: This study aimed to evaluate the effect of 6-month weight loss diets on erythrocyte membrane omega-3 PUFA composition of NAFLD adults, and to evaluate the potential relationship between erythrocyte membrane omega-3 PUFAs and hepatic health markers. METHODS: In this secondary analysis of the Fatty Liver in Obesity study, erythrocyte membranes were analyzed by gas chromatography in 54 subjects with liver steatosis detected by ultrasonography who achieved a weight loss >5% after the follow-up. Baseline and 6-month evaluation included hepatic acoustic radiation force impulse elastography and magnetic resonance imaging, anthropometry, body composition, and biochemical determinations. RESULTS: After the follow-up, α-linolenic acid (ALA) proportion significantly increased in erythrocyte membranes, whereas eicosapentaenoic acid (EPA) showed no statistical difference and docosapentaenoic acid decreased. Both the changes in erythrocyte membrane ALA and EPA were positively associated with dietary ALA. Regression analyses evidenced that the changes in erythrocyte membrane ALA and EPA were inversely associated with the changes in liver stiffness and liver iron content, respectively. CONCLUSION: The adherence to weight loss strategies for 6 months led to changes in erythrocyte membrane omega-3 PUFA composition, which in turn were associated with changes in hepatic markers, suggesting that these fatty acids accompany the improvements in the liver during a dietary treatment. These findings show that beyond weight loss, the composition of the diet has an important role in the management of NAFLD.

Evaluation of Skin Permeation and Retention of Topical Dapsone in Murine Cutaneous Leishmaniasis Lesions.

The oral administration of dapsone (DAP) for the treatment of cutaneous leishmaniasis (CL) is effective, although serious hematological side effects limit its use. In this study, we evaluated this drug for the topical treatment of CL. As efficacy depends on potency and skin penetration, we first determined its antileishmanial activity (IC50 = 100 µM) and selectivity index in vitro against Leishmania major-infected macrophages. In order to evaluate the skin penetration ex vivo, we compared an O/W cream containing DAP that had been micronized with a pluronic lecithin emulgel, in which the drug was solubilized with diethylene glycol monoethyl ether. For both formulations we obtained similar low flux values that increased when the stratum corneum and the epidermis were removed. In vivo efficacy studies performed on L. major-infected BALB/c mice revealed that treatment not only failed to cure the lesions but made their evolution and appearance worse. High plasma drug levels were detected and were concomitant with anemia and iron accumulation in the spleen. This side effect was correlated with a reduction of parasite burden in this organ. Our results evidenced that DAP in these formulations does not have an adequate safety index for use in the topical therapy of CL.

Influence of Two Polymer-Based Superplasticizers (Poly-naphthalene Sulfonate, PNS, and Lignosulfonate, LS) on Compressive and Flexural Strength, Freeze-Thaw, and Sulphate Attack Resistance of Lime-Metakaolin Grouts.

A new range of grouts prepared by air lime and metakaolin (MK) as a pozzolanic admixture has been obtained by using as dispersing agents two polymers, namely poly-naphthalene sulfonate (PNS) and lignosulfonate (LS), with the aim of improving the fluidity of the fresh grouts. Fluidity and setting times of the grouts were assessed. Differences in the molecular architecture and in the anionic charge density explained the different adsorption of the polymers and the different performance. The higher anionic charge of PNS and its linear shape explained its better adsorption and effectiveness. The pozzolanic reaction was favoured in grouts with PNS, achieving the highest values of compressive strength (4.8 MPa after 182 curing days). The addition of PNS on lime grouts slightly decreased the frost resistance of the grouts (from 24 freeze-thaw cycles for the polymer-free samples to 19 or 20 cycles with 0.5 or 1 wt % of PNS). After the magnesium sulphate attack, grouts were altered by decalcification of hydrated phases and by formation of hexahydrite and gypsum. A protective role of portlandite against magnesium sulphate attack was clearly identified. Accordingly, the polymer LS, which preserves a significant amount of Ca(OH)2, could be an alternative for the obtaining of grouts requiring high sulphate attack resistance.

The Effect of TiO2 Doped Photocatalytic Nano-Additives on the Hydration and Microstructure of Portland and High Alumina Cements.

Mortars with two different binders (Portland cement (PC) and high alumina cement (HAC)) were modified upon the bulk incorporation of nano-structured photocatalytic additives (bare TiO2, and TiO2 doped with either iron (Fe-TiO2) or vanadium (V-TiO2)). Plastic and hardened state properties of these mortars were assessed in order to study the influence of these nano-additives. Water demand was increased, slightly by bare TiO2 and Fe-TiO2, and strongly by V-TiO2, in agreement with the reduction of the particle size and the tendency to agglomerate. Isothermal calorimetry showed that hydration of the cementitious matrices was accelerated due to additional nucleation sites offered by the nano-additives. TiO2 and doped TiO2 did not show pozzolanic reactivity in the binding systems. Changes in the pore size distribution, mainly the filler effect of the nano-additives, accounted for the increase in compressive strengths measured for HAC mortars. A complex microstructure was seen in calcium aluminate cement mortars, strongly dependent on the curing conditions. Fe-TiO2 was found to be homogeneously distributed whereas the tendency of V-TiO2 to agglomerate was evidenced by elemental distribution maps. Water absorption capacity was not affected by the nano-additive incorporation in HAC mortars, which is a favourable feature for the application of these mortars.

Selenium content of Spanish infant formulae and human milk: influence of protein matrix, interactions with other trace elements and estimation of dietary intake by infants.

The selenium content of infant formulae varies as a result of differences in the amount of intrinsic selenium compounds. Manufacturers have been gradually changing the protein profile of infant formulae to reflect human milk contents more closely. Because of these variations in infant formula composition and their potential impact on selenium content, this trace element was analysed with regard to the different protein sources. The aims of this study were to determine the selenium content in infant formulae sold commercially in Spain, to estimate a daily dietary intake for infants fed on formulae and to compare with the selenium provided by Spanish breast milk samples used as a reference. We have also identified certain trace elements added to formulae which interact with selenium according to the type and protein matrix of the infant formulae. Selenium concentration was determined by inductively coupled plasma atomic emission spectrometry (ICP-AES) with a hydride generator. The selenium concentrations in human milk and infant formulae determined in this study are similar to those found by other researchers in different countries. The daily selenium intake from the formulae studied was estimated according to the recommended doses from the manufacturers. The theoretical selenium intake of nursed infants has been studied in relation to the Recommended Dietary Allowance (RDA: 10 microg Se/day) and the specific recommendations for infant formula nutrient contents (10-35 microg Se/L) set by the Expert Panel of life Sciences Research Office (LSRO) of the American Society for Nutritional Sciences. According to our results, on an overall view, infants fed on the studied infant formulae have an intake between basal and normative requirements. This might be considered as providing an adequate selenium supply. However, the intake of setenium provided by several formulae included in this research did not reach the RDA for the first month of neonate life.

Optimization of a gelled emulsion intended to supply ω-3 fatty acids into meat products by means of response surface methodology.

The optimization of a gelled oil-in-water emulsion was performed for use as fat replacer in the formulation of ω-3 PUFA-enriched cooked meat products. The linseed oil content, carrageenan concentration and surfactant-oil ratio were properly combined in a surface response design for maximizing the hardness and minimizing the syneresis of the PUFA delivery system. The optimal formulation resulted in a gelled emulsion containing 40% of oil and 1.5% of carrageenan, keeping a surfactant-oil ratio of 0.003. The gel was applied as a partial fat replacer in a Bologna-type sausage and compared to the use of an O/W emulsion also enriched in ω-3. Both experimental sausages contributed with higher ω-3 PUFA content than the control. No sensory differences were found among formulations. The selected optimized gelled oil-in-water emulsion was demonstrated to be a suitable lipophilic delivery system for ω-3 PUFA compounds and applicable in food formulations as fat replacer.

Healthy reduced-fat Bologna sausages enriched in ALA and DHA and stabilized with Melissa officinalis extract.

Reduced-energy and reduced-fat Bologna products enriched with ω-3 polyunsaturated fatty acids were formulated by replacing the pork back-fat by an oil-in-water emulsion containing a mixture of linseed-algae oil stabilized with a lyophilized Melissa officinalis extract. Healthier composition and lipid profile was obtained: 85 kcal/100 g, 3.6% fat, 0.6 g ALA and 0.44 g DHA per 100 g of product and ω-6/ω-3 ratio of 0.4. Technological and sensory problems were not detected in the new formulations. Reformulation did not cause oxidation problems during 32 days of storage under refrigeration. The results suggest that it is possible to obtain reduced-fat Bologna-type sausages rich in ALA and DHA and stabilized with natural antioxidants, applying the appropriate technology without significant effects on the sensory quality, yielding interesting products from a nutritional point of view.

Topical treatment of L. major infected BALB/c mice with a novel diselenide chitosan hydrogel formulation.

Topical therapy is the ideal outpatient treatment of cutaneous leishmaniasis (CL) because of the ease of administration and lower cost. It could be suitable as monotherapy for localized cutaneous leishmaniasis (LCL) or in combination with systemic therapies for more severe forms of the disease. Although paromomycin (PM) ointment can be recommended for the treatment of LCL caused by Leishmaniamajor, a more effective topical treatment should be achieved regarding the physicochemical properties of this aminoglucoside and its rather poor intrinsic antileishmanial activity, that hampers the accumulation of enough amount of drug in the dermis (where the infected macrophages home) to exert its activity. In this work, we determined a 50% effective dose of 5.6 µM for a novel compound, bis-4-aminophenyldiselenide, against L. major intracellular amastigotes. This compound and PM were formulated in chitosan hydrogels and ex vivo permeation and retention studies in the different skin layers were performed with pig ear skin in Franz diffusion cells. The results showed that less than 2-4% of the diselenide drug penetrated and permeated through the skin. In contrast, the percentage of PM penetration was about 25-60% without important retention in the skin. When topically applied to lesions of L. major infected BALB/c mice, the novel diselenide chitosan formulation was unable to slow lesion progression and reduce parasite burden. Considerations during the process of novel drug development and formulation discovery algorithm for CL are discussed.

Low energy and carbohydrate intake associated with higher total antioxidant capacity in apparently healthy adults.

OBJECTIVES: The aim of this study was to investigate the associations between plasma total antioxidant capacity (TAC) and anthropometric, biochemical, clinical, and dietary measurements in young and apparently healthy individuals. METHODS: We evaluated 156 individuals (91 women and 65 men; ages 23.1 ± 3.5 y; body mass index 22 ± 2.9 kg/m(2)) for anthropometrics, biochemical markers, clinical, dietary, and some components of the antioxidant defense system, including the plasma TAC. Statistical analyses were performed to detect differences between individuals with TAC higher and lower than the mean value and to screen the associations between TAC and variables of interest. A linear regression model was fitted to identify TAC predictors. RESULTS: Daily caloric intake and macronutrient consumption were lower in individuals who exhibited the highest TAC values (P < 0.05). Linear regression analysis showed that daily calories and carbohydrate intake was a possible negative TAC predictor (P < 0.05). Nevertheless, there was no difference in the values of oxidized low-density lipoprotein in the individuals separated by means of TAC. In contrast, individuals whose plasma TAC values were above the mean showed higher low-density lipoprotein cholesterol concentrations, total cholesterol/high-density lipoprotein cholesterol values, and selenium in nails (P < 0.05). CONCLUSIONS: In physiological conditions, the caloric intake level seems to be an important factor to act in the modulation of plasma TAC, before establishing anthropometric impairments of body or metabolic composition, or both. Additionally, the plasma TAC increase may be able to act as a compensatory mechanism.