The impact Of high-intensity interval training On functioning And health-related quality Of life In post-stroke patients: A systematic review With meta-analysis.

OBJECTIVE: To examine the effects of high-intensity interval training on the functioning and health-related quality of life of post-stroke patients. METHODS: We searched the following electronic databases: MEDLINE/Pubmed, Cochrane Central Register of Controlled Trials, PEDro database, and Scielo up to January 2022 for randomized controlled trials that investigated the effects of high-intensity interval training in post-stroke patients. Two reviewers selected the studies independently. Study quality was evaluated using the PEDro scale. The mean difference (MD), standard mean difference (SMD), and 95% confidence intervals (CIs) were calculated. RESULTS: Nine studies met the study criteria (375 patients). The age of the participants ranged from 55.8 to 72.1 years. The studies included patients within 2 weeks of stroke onset to patients longer than 1 month of stroke. High-intensity interval training resulted in improvement in cardiorespiratory fitness (peak oxygen uptake) MD (3.8 mL/kg/min, 95% CI: 2.62, 5.01, n = 91), balance MD 5.7 (95% CI: 3.50, 7.91; N = 64), and gait speed SMD (0.2 m/s; 95% CI: 0.05, 0.27; N = 100) compared with continuous aerobic training. The health-related quality of life did not differ between the groups. Compared to usual care, high-intensity interval training improved the cardiorespiratory fitness SMD (0.5 95% CI: 0.14, 0.81, n = 239). No serious adverse events were observed. CONCLUSIONS: The findings of this systematic review show that high-intensity interval training was more efficient than continuous aerobic training to gain cardiorespiratory fitness, balance and gait speed in post-stroke patients. In addition, compared to usual care, high-intensity interval training improved cardiorespiratory fitness.

Synchrotron X-ray diffraction investigation of the surface condition of artefacts from King Henry VIII's warship the Mary Rose.

Synchrotron X-ray diffraction (XRD) measured on the XMaS beamline at the ESRF was used to characterize the alloy composition and crystalline surface corrosion of three copper alloy Tudor artefacts recovered from the undersea wreck of King Henry VIII's warship the Mary Rose. The XRD method adopted has a dynamic range ∼1:105 and allows reflections <0.002% of the height of major reflections in the pattern to be discerned above the background without smoothing. Laboratory XRD, scanning electron microscopy-energy dispersive spectroscopy, synchrotron X-ray fluorescence and X-ray excited optical luminescence-X-ray near-edge absorption structure were used as supporting techniques, and the combination revealed structural and compositional features of importance to both archaeology and conservation. The artefacts were brass links believed to be fragments of chainmail and were excavated from the seabed during 1981 and 1982. Their condition reflects very different treatment just after recovery, viz. complete cleaning and conservation, chemical corrosion inhibition and chloride removal only, and distilled water soaking only (to remove the chlorides). The brass composition has been determined for all three at least in the top 7 µm or so as Cu(73%)Zn(27%) from the lattice constant. Measurement of the peak widths showed significant differences in the crystallite size and microstrain between the three samples. All of the links are found to be almost chloride-free with the main corrosion products being spertiniite, sphalerite, zincite, covellite and chalcocite. The balance of corrosion products between the links reflects the conservation treatment applied to one and points to different corrosion environments for the other two.

Liposomal Entrapment of 4-Nerolidylcatechol: Impact on Phospholipid Dynamics, Drug Stability and Bioactivity.

Liposomes containing 4-nerolidylcatechol (4-NC), the major metabolite isolated from Pothomorphe umbellata, were obtained and characterized. Influence of liposomal encapsulation on chemical stability of 4-NC and on cytotoxicity profile of this drug was evaluated. Soybean phosphatidylcholine liposomes were prepared by lipid film hydration followed by extrusion. Entrapment efficiency for 4-NC was approximately 92%. Mean diameter of liposomes was 100 nm with a polydispersity index below 0.13. Liposomal 4-NC (L4-NC) and free drug (F4-NC) were submitted to forced degradation assays, monitored by HPLC. Photodegradation assay followed ICH Guidelines, using a photostability chamber equipped with both UV and white light sources. Liposomal encapsulation was able to markedly reduce 4-NC degradation rates under all the conditions tested. L4-NC showed a half-live approximately 15% higher than F4-NC under light exposure. After 72 hours, acid and base hydrolysis of F4-NC lead to 13 and 16% of degradation, respectively. However, no degradation was observed in L4-NC. EPR spectra of liposomal membrane showed that greatest changes in membrane properties were obtained when 5-doxyl stearic acid was used as the spin label, indicating a marked decrease in the fluidity of the bilayer. Following incubation with K562 cells, 4-NC showed a concentration-dependent cytotoxicity profile, while L4-NC exhibited a time and concentration-dependent profile, consistent with a controlled drug release system. F4-NC induced extensive hemolysis under isotonic conditions; conversely liposomal encapsulation protected erythrocytes from 4-NC induced lysis. Liposomal 4-NC resulted in a hemocompatibility and stable formulation, representing a viable drug delivery system to further investigate in vivo performances of 4-NC in pre clinical studies.

Fsy1, the sole hexose-proton transporter characterized in Saccharomyces yeasts, exhibits a variable fructose:H(+) stoichiometry.

In the model yeast Saccharomyces cerevisiae, hexose uptake is mediated exclusively by a family of facilitators (Hxt, hexose transporters). Some other Saccharomyces species (e.g. Saccharomyces bayanus and Saccharomyces pastorianus) possess, in addition, a specific fructose transporter (Fsy1, fructose symporter) that has been previously described to function as a proton symporter. In the present work, we compared growth of a yeast strain in which FSY1 occurs naturally in anaerobic, fructose- and glucose-limited chemostat cultures. Especially at low specific growth rates, fructose-proton symport was shown to have a strong impact on the biomass yield on sugar. We subsequently employed energized hybrid plasma membrane vesicles to confirm previous observations concerning the mode of operation and specificity of Fsy1 mediated transport. Surprisingly, these experiments suggested that the carrier exhibits an unusual fructose:H(+) stoichiometry of 1:2. This energetically expensive mode of operation was also found consistently in vivo, in shake flask and in chemostat cultures, and both when Fsy1 is the sole transporter and when the Hxt carriers are present. However, it is observed only when Fsy1 is operating at higher glycolytic fluxes, a situation that is normally prevented by downregulation of the gene. Taken together, our results suggest the possibility that fructose symport with more than one proton may constitute an energetically unfavorable mode of operation of the Fsy1 transporter that, in growing cultures, is prevented by transcriptional regulation.

Modulation of Alternaria infectoria cell wall chitin and glucan synthesis by cell wall synthase inhibitors.

The present work reports the effects of caspofungin, a ß-1,3-glucan synthase inhibitor, and nikkomycin Z, an inhibitor of chitin synthases, on two strains of Alternaria infectoria, a melanized fungus involved in opportunistic human infections and respiratory allergies. One of the strains tested, IMF006, bore phenotypic traits that conferred advantages in resisting antifungal treatment. First, the resting cell wall chitin content was higher and in response to caspofungin, the chitin level remained constant. In the other strain, IMF001, the chitin content increased upon caspofungin treatment to values similar to basal IMF006 levels. Moreover, upon caspofungin treatment, the FKS1 gene was upregulated in IMF006 and downregulated in IMF001. In addition, the resting ß-glucan content was also different in both strains, with higher levels in IMF001 than in IMF006. However, this did not provide any advantage with respect to echinocandin resistance. We identified eight different chitin synthase genes and studied relative gene expression when the fungus was exposed to the antifungals under study. In both strains, exposure to caspofungin and nikkomycin Z led to modulation of the expression of class V and VII chitin synthase genes, suggesting its importance in the robustness of A. infectoria. The pattern of A. infectoria phagocytosis and activation of murine macrophages by spores was not affected by caspofungin. Monotherapy with nikkomycin Z and caspofungin provided only fungistatic inhibition, while a combination of both led to fungal cell lysis, revealing a strong synergistic action between the chitin synthase inhibitor and the ß-glucan synthase inhibitor against this fungus.

Development and initial evaluation of a combustion-based sample introduction system for direct isotopic analysis of mercury in solid samples via multi-collector ICP-mass spectrometry.

High-precision isotopic analysis of mercury (Hg) using multi-collector ICP-mass spectrometry (MC-ICP-MS) is a powerful method for obtaining insight into the sources, pathways and sinks of this toxic metal. Modification of a commercially available mercury analyzer (Teledyne Leeman Labs, Hydra IIc - originally designed for quantification of Hg through sample combustion, collection of the Hg vapor on a gold amalgamator, subsequent controlled release of Hg and detection using cold vapor atomic absorption spectrometry CVAAS) enabled the system to be used for the direct high-precision Hg isotopic analysis of solid samples using MC-ICP-MS - i.e., without previous sample digestion and subsequent dilution. The changes made to the mercury analyzer did not compromise its (simultaneous) use for Hg quantification via CVAAS. The Hg vapor was mixed with a Tl-containing aerosol produced via pneumatic nebulization, creating wet plasma conditions, and enabling the use of Tl as an internal standard for correction of instrumental mass discrimination. Accurate and precise (0.10 ‰ 2SD, δ202Hg, n = 5) results were obtained for an in-house standard solution of Hg (20 ng Hg sample intake). Initial validation relied on the successful analysis of two solid certified reference materials of biological origin (BCR CRM 464 Tuna fish and NRC-CNRC TORT-3 Lobster hepatopancreas). It was shown that instrumental mass discrimination can be adequately corrected for by relying on the use of an aqueous Hg standard solution (NIST SRM 3133), without the need of matrix-matching. The novel setup developed thus allows for direct high-precision isotopic analysis of Hg in solid samples, thus enhancing the sample throughput. It is also suited for samples for which low amounts are available only and/or that are characterized by low Hg concentrations.

Efficacy and safety of very early mobilization after thrombolysis in acute ischemic stroke: a randomized clinical trial.

BACKGROUND: Stroke has a deleterious impact on human health due to its high incidence, degree of disabling sequelae and mortality, constituting one of the main causes of death and disability worldwide. OBJECTIVES: This study aimed to assess the efficacy and safety of very early mobilization (VEMG) after thrombolysis in functional recovery in patients with acute ischemic stroke. METHODS: The present study was an open, prospective, randomized study, with no blinded outcome, carried out in the stroke unit of a tertiary referral hospital located in Salvador-Bahia, Brazil. The primary outcome was the level of functional independence. Secondary outcomes were functional mobility, balance, complications within 7 days of hospitalization and 90 days after hospital discharge, and length of stay. OUTCOMES: A total of 104 patients with ischemic stroke who received thrombolytic treatment between August 2020 and July 2021 were prospectively recruited to the study. Of these, 51 patients received VEMG within 24 h of the ictus and another 53 patients receiving usual care (UCG) with mobilization 24 h after the ictus. When compared to the usual care, the VEMG group was not associated with a significant reduction in the risk of the primary outcome (relative risk [95% confidence intervals]: 0.74 [0.339-1.607]) or any of the secondary outcomes. CONCLUSION: In this study, the strategy of early mobilization after thrombolysis in ischemic stroke was safe, but without evidence of short-term benefit. Brazilian Registry of Clinical Trials under the registry (registry number: RBR-8bgcs3).

Pre-clinical safety of topically administered sunitinib-loaded lipid and polymeric nanocarriers targeting corneal neovascularization.

Three different types of sunitinib-loaded (SUN-loaded) nanocarriers were compared, aiming at the topical treatment of corneal neovascularization (CNV): polymeric nanospheres (NS), liposomes (LIP), and solid lipid nanoparticles (SLN). Three out of eleven formulations prepared for an optimization study - the best SUN-loaded nanocarrier of each assessed type (NS, LIP, and SLN) - were selected, based on their size, polydispersity index (PdI), drug load (DL), and encapsulation efficiency (EE). These three optimal formulations were further characterized by nanoparticle tracking analysis (NTA), electron paramagnetic resonance (EPR) spectroscopy, and zeta potential. In vitro SUN release profiles were obtained for the optimal formulations, along with ex vivo corneal permeability/retention studies, and ocular tolerance assays, namely: the bovine corneal opacity and permeability (BCOP) assay, the HET-CAM test (hen's egg test - chorioallantoic membrane), and hemolytic potential (HP) assay. None of the optimal formulations exhibited toxicity or potential for ocular irritation. SLN showed higher surface fluidity, drug release more suitable for topical ocular applications, besides greater SUN corneal retention. Our results suggest that SLN are the best CNV-targeting SUN-loaded nanocarriers for clinical translation when compared to their NS and LIP analogues.

ß(1,3)-glucan synthase complex from Alternaria infectoria, a rare dematiaceous human pathogen.

The fungal cell wall polymer ß-(1,3)-D-glucan is synthesized by the enzyme ß-(1,3)- D-glucan synthase that is a complex composed of at least two proteins, Rho1p and Fks1p. Here, we report the nucleotide sequence of a single FKS gene and of the regulatory unit, RHO1 from the dematiaceous pathogenic fungus Alternaria infectoria. The predicted AiFks and AiRho share, respectively, 93% and 100% identity with that of Drechslera tritici-repentis. We also report that the sensitivity to caspofungin of eight different A. infectoria clinical strains is similar, with a MIC > 32 µg/ml and a MEC of 1 µg/ml, except for one strain which had a MEC of 1.4 µg/ml. This same strain exhibited one substitution at the hot spot 2, S1405A, compatible with less susceptible phenotypes, with the other seven strains having no mutations in either hot spot 1 or 2. The relative quantification of the expression of AiFKS and of AiRHO demonstrated a decrease in response to an exposure to caspofungin at 0.5 µg/ml.

Nanostructured lipid carriers for hair follicle-targeted delivery of clindamycin and rifampicin to hidradenitis suppurativa treatment.

Hidradenitis suppurativa is a chronic and debilitating inflammatory condition related to a permanent obstruction of the pilosebaceous units. Until nowadays, therapeutic options are unsatisfactory. Here, we propose nanostructured lipid carriers (NLC) entrapping an association of clindamycin phosphate (CDM) and rifampicin (RIF) as a topical alternative for the treatment of the disease. Chemical compatibility between the drugs was demonstrated using thermal analysis combined with ATR-FTIR and X-ray powder diffraction assays. Nanocarriers' diameter was narrowly distributed (polydispersity index = 0.2) around 400 ± 14 nm, they possess a negative surface charge (-48.9 ± 0.7 mV) and high drug entrapment efficiencies (80.2 ± 0.4 % and 93.4 ± 0.7 % for CDM and RIF, respectively). The formulation proved to be safe for the topical application, as it was non-irritant on both HET-CAM and reconstructed human epidermis (RHE) assays. Spin-label EPR indicated an NLC affinity for the lipidic domains of stratum corneum, which could benefit the targeting of the sebaceous units. Indeed, when applied on the skin in vitro, even when mimicking the sebaceous condition, NLC accumulated into the hair follicles openings, not altering the amount of accumulated CDM and significantly increasing by 12-fold the uptake of RIF in these structures. In conclusion, developed NLC formulation incorporating the antibiotics CDM and RIF is a promising strategy for the topical treatment of hidradenitis suppurativa or other infections that may affect the pilosebaceous units.

Enhanced nail delivery of voriconazole-loaded nanomicelles by thioglycolic acid pretreatment: A study of protein dynamics and disulfide bond rupture.

This work aimed to select an effective penetration enhancer (PE) for nail pretreatment, develop voriconazole (VOR)-loaded nanomicelles, and evaluate their ability to deliver VOR to the nail. A complete analysis of nail protein dynamics, bond rupture, and microstructure was performed. Alternative methods as electron paramagnetic resonance (EPR) and the Ellman's reagent (DTNB) assay were also evaluated. Nanomicelles were produced and characterized. The PE hydrated the hooves, following the order: urea ≈ cysteine ≈ glycolic acid < thioglycolic acid (TGA) < NaOH. SEM images and methylene blue assay showed enlarged pores and roughness of porcine hooves after incubation with NaOH and TGA. EPR was demonstrated to be the most sensitive technique. DTNB assay quantified higher thiol groups for samples treated with TGA (p < 0.05). A stratigraphic analysis with Raman spectroscopy demonstrated that hooves treated with TGA presented a higher SH/SS ratio at the edges, affecting protein secondary structure. In vitro permeation studies demonstrated significant VOR permeation (29.44 ± 6.13 µg/cm2), 10-fold higher than previous studies with lipid nanoparticles. After TGA pretreatment, VOR permeation was further enhanced (3-fold). TGA pretreatment followed by VOR-loaded nanomicelles demonstrates a promising approach for onychomycosis treatment. The novel methods for protein analysis were straightforward and helpful.

Reproducibility of respiratory mechanics measurements in patients on invasive mechanical ventilation. / Reprodutibilidade das mensurações da mecânica respiratória em pacientes sob ventilação mecânica invasiva.

OBJECTIVE: To evaluate the intra- and interexaminer reproducibility of measurements of the resistance and static and dynamic compliance of the respiratory system in patients on mechanical ventilation. METHODS: This was an analytical study conducted with individuals aged ≥ 18 years who were on invasive mechanical ventilation and had no clinical diagnosis of respiratory system disease and/or chest abnormality. Three measurements of respiratory mechanics were performed with a 1-minute interval between them. The first and third measurements were performed by examiner A, the second by examiner B. The values for the resistance and static and dynamic compliance of the respiratory system were compared using the intraclass correlation coefficient. RESULTS: A total of 198 measurements of respiratory mechanics were performed for 66 patients on mechanical ventilation. The patients had a mean age of 52.6 ± 18.6 years and a mean body mass index of 21.6 ± 2.1kg/m2; a surgical profile (61.5%) and female sex (53.8%) were predominant. Mean values were obtained for the three measurements of respiratory system resistance (A1: 15.7 ± 6.8cmH2O/L/s; B1: 15.7 ± 6.4cmH2O/L/s and A2: 15.9 ± 6.2cmH2O/L/s), respiratory system static compliance (A1: 42.1 ± 13.7mL/cmH2O; B1: 42.4 ± 14.6mL/cmH2O and A2: 42.2 ± 14.5mL/cmH2O) and respiratory system dynamic compliance (A1: 21.3 ± 7.3mL/cmH2O; B1: 21.4 ± 7.5mL/cmH2O and A2: 21.3 ± 6.2mL/cmH2O). The intraclass correlation coefficient was also calculated for respiratory system resistance (R = 0.882 and p = 0.001; R = 0.949 and p = 0.001 - interexaminer A1 versus B and B versus A2, respectively; R = 0.932 and p = 0.001 - intraexaminer); respiratory system static compliance (R = 0.951 and p = 0.001; R = 0.958 and p = 0.001 - interexaminer A1 versus B and B versus A2, respectively; R = 0.965 and p = 0.001 - intraexaminer) and respiratory system dynamic compliance (R = 0.957 and p = 0.001; R = 0.946 and p = 0.001 - interexaminer A1 versus B and B versus A2, respectively; R = 0.926 and p = 0.001 - intraexaminer). CONCLUSION: The measurements of resistance and static and dynamic compliance of the respiratory system show good intra- and interexaminer reproducibility for ventilated patients.

OBJETIVO: Avaliar a reprodutibilidade intra e interexaminador das mensurações da resistência e das complacências estática e dinâmica do sistema respiratório em pacientes sob ventilação mecânica. MÉTODOS: Trata-se de estudo analítico realizado com indivíduos com idade ≥ 18 anos, em ventilação mecânica invasiva, que não tinham diagnóstico clínico de doença do aparelho respiratório e/ou anormalidade de caixa torácica. Foram realizadas três aferições da mecânica respiratória com intervalo de 1 minuto entre elas. A primeira e a terceira aferições foram realizadas pelo avaliador A e a segunda aferição, pelo avaliador B. A comparação dos valores de resistência e complacências estática e dinâmica do sistema respiratório foi calculada por meio do coeficiente de correlação intraclasse. RESULTADOS: Foram realizadas 198 aferições da mecânica respiratória em 66 pacientes sob ventilação mecânica, com idade média de 52,6 ± 18,6 anos, índice de massa corporal médio de 21,6 ± 2,1kg/m2, predomínio do perfil cirúrgico (61,5%) e sexo feminino (53,8%). Foram obtidos valores médios das três aferições para resistência do sistema respiratório (A1: 15,7 ± 6,8cmH2O/L/s; B1: 15,7 ± 6,4cmH2O/L/s e A2: 15,9 ± 6,2cmH2O/L/s), para complacência estática do sistema respiratório (A1: 42,1 ± 13,7mL/cmH2O; B1: 42,4 ± 14,6mL/cmH2O e A2: 42,2 ± 14,5mL/cmH2O) e para complacência dinâmica do sistema respiratório (A1: 21,3 ± 7,3mL/cmH2O; B1: 21,4 ± 7,5mL/cmH2O e A2: 21,3 ± 6,2mL/cmH2O). Também foram encontrados valores do coeficiente de correlação intraclasse para resistência do sistema respiratório (R = 0,882 e p = 0,001; R = 0,949 e p = 0,001 - interexaminadores A1 versus B e B versus A2, respectivamente; R = 0,932 e p = 0,001 - intraexaminador); complacência estática do sistema respiratório (R = 0,951 e p = 0,001; R = 0,958 e p = 0,001 - interexaminadores A1 versus B e B versus A2, respectivamente; R = 0,965 e p = 0,001 - intraexaminador) e complacência dinâmica do sistema respiratório (R = 0,957 e p = 0,001; R = 0,946 e p = 0,001 - interexaminadores A1 versus B e B versus A2 respectivamente; R = 0,926 e p = 0,001 - intraexaminador). CONCLUSÃO: A mensuração de mecânica respiratória apresenta boa reprodutibilidade intra e interexaminador para as aferições de resistência e complacências estática e dinâmica do sistema respiratório em pacientes ventilados.

Besifloxacin liposomes with positively charged additives for an improved topical ocular delivery.

Topical ophthalmic antibiotics show low efficacy due to the well-known physiological defense mechanisms of the eye, which prevents the penetration of exogenous substances. Here, we aimed to incorporate besifloxacin into liposomes containing amines as positively charged additives and to evaluate the influence of this charge on drug delivery in two situations: (i) iontophoretic and (ii) passive treatments. Hypothesis are (i) charge might enhance the electromigration component upon current application improving penetration efficiency for a burst drug delivery, and (ii) positive charge might prolong formulation residence time, hence drug penetration. Liposomes elaborated with phosphatidylcholine (LP PC) or phosphatidylcholine and spermine (LP PC: SPM) were stable under storage at 6 ºC for 30 days, showed mucoadhesive characteristics, and were non-irritant, according to HET-CAM tests. Electron paramagnetic resonance spectroscopy measurements showed that neither the drug nor spermine incorporations produced evident alterations in the fluidity of the liposome's membranes, which retained their structural stability even under iontophoretic conditions. Mean diameter and zeta potential were 177.2 ± 2.7 nm and - 5.7 ± 0.3 mV, respectively, for LP PC; and 175.4 ± 1.9 nm and + 19.5 ± 1.0 mV, respectively, for LP PC:SPM. The minimal inhibitory concentration (MIC) and the minimal bactericide concentration (MBC) of the liposomes for P. aeruginosa showed values lower than the commercial formulation (Besivance). Nevertheless, both formulations presented a similar increase in permeability upon the electric current application. Hence, liposome charge incorporation did not prove to be additionally advantageous for iontophoretic therapy. Passive drug penetration was evaluated through a novel in vitro ocular model that simulates the lacrimal flow and challenges the formulation resistance in the passive delivery situation. As expected, LP PC: SPM showed higher permeation than the control (Besivance). In conclusion, besifloxacin incorporation into positively charged liposomes improved passive topical delivery and can be a good strategy to improve topical ophthalmic treatments.

Iontophoresis enhances voriconazole antifungal potency and corneal penetration.

Strategies to enhance corneal penetration of voriconazole (VOR) could improve the treatment of fungal keratitis. Here, we evaluated the use of iontophoresis for ocular VOR delivery from either: (i) a cyclodextrin inclusion complex (CD VOR), (ii) a liposome (LP VOR), and (iii) a chitosan-coated liposome (LP VOR CS). LP VOR CS presented mean diameter of 139.2 ±â€¯1.3 nm and zeta potential equal to + 3.3 ±â€¯1.5 mV compared to 134.6 ±â€¯1.7 and -8.2 ±â€¯3.0 mV of LP VOR, which, together with mucin mucoadhesion study, confirmed chitosan-coating. Both drug and liposomal formulations were stable under the influence of an applied electric current. Interestingly, in vitro studies in Candida glabrata culture indicated a decrease in VOR MIC values following iontophoresis (from 0.28 to 0.14 µg/mL). Iontophoresis enhanced drug penetration into the cornea. After 10 min of a 2 mA/cm2 applied current, corneal retained amounts were 45.4 ±â€¯11.2, 30.4 ±â€¯2.1 and 30.6 ±â€¯2.9 µg/cm2 for, respectively, CD VOR, LP VOR, and LP VOR CS. In conclusion, iontophoresis increases drug potency and enhances drug penetration into the cornea, showing potential to be used as "an emergency burst delivery approach".

Terpenes increase the partitioning and molecular dynamics of an amphipathic spin label in stratum corneum membranes.

In this work, the interaction of the skin penetration enhancers dl-menthol, alpha-terpineol, 1,8-cineole and (+)-limonene with the uppermost skin layer, the stratum corneum and with multilamellar vesicles from 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) is investigated by electron paramagnetic resonance (EPR) spectroscopy of the small spin label 2,2,6,6,-tetramethylpiperedine-1-oxyl (TEMPO), which partitions the aqueous and hydrocarbon phases. The EPR spectrum allows for the determination of the actual partition coefficient and the rotational diffusion rates of the spin probe in the two environments. The enthalpy changes, DeltaH degrees , to transfer the spin probe from the aqueous to the hydrocarbon phase, as well as the activation energies associated to its rotational motion, were considerably smaller for stratum corneum, indicating less pronounced thermal reorganization. For DPPC, the terpenes increased both the partition coefficient and the rotational diffusion rate of the spin label in the membrane, except in the liquid-crystalline phase, while these increases in stratum corneum were observed in the entire temperature range measured with the exception of the rotational motion parameter for dl-menthol and alpha-terpineol at temperatures below their melting point (32-41 degrees C). It is suggested that the terpenes effectively acting as spacers in the membrane fluidize the lipids and cause ruptures in the hydrogen-bonded network of the polar interface.

Development of lamellar gel phase emulsion containing baru oil (Dipteryx alata Vog.) as a prospective delivery system for cutaneous application.

The rational design of emulsions requires study of the main factors that influence their formation, physicochemical properties and, consequently, stability and performance. The use of vegetable oils in the pharmaceutical and cosmetic industries has recently become attractive. Dipteryx alata Vogel (D. alata) is an oleaginous species native to Brazil. The seeds of this species contain highly unsaturated oil with significant amounts of tocopherols and phytosterols, representing an important source of agents capable of combatting oxidative processes. In this work, a lamellar gel phase emulsion using oil extracted from the seeds of D. alata (baru) was developed. The steps involved in the development of this research were as follows: 1) development of formulations and 2) in vitro assays by simulating the evaporation of the final product after application to the skin and Electron paramagnetic resonance spectroscopy (EPR) of fatty acid spin labels was used to investigate the profile of interaction of the dispersed systems with stratum corneum (SC) lipids. The results indicate that the developed system shows no signs of instability during the storage period. Moreover, EPR studies indicated that D. alata oil and especially the developed formulation were able to increase SC lipid fluidity and extract a fatty-acid spin label from the lipid domain structures of SC, demonstrating its potential to act as a drug or skin care vehicle.

An EPR spin probe study of the interactions between PC liposomes and stratum corneum membranes.

The electron paramagnetic resonance (EPR) spin labeling methodology was used to analyze the interactions of phosphatidylcholine (PC) liposomal formulations that are commonly used as transepidermal drug delivery systems with stratum corneum (SC) membranes. The lipid dynamics of five liposome formulations were evaluated to study the influences of sorbitan monooleate (Span80), cholesterol, and cholesterol with the charged lipids 2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-distearoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DSPG) on the molecular dynamics of PC vesicles. The EPR spectra of 5-doxyl-stearic acid (5-DSA) showed that the addition of Span80 to the liposomes increased the lipid fluidity, whereas cholesterol had the opposite effect, and the combination of charged lipids and cholesterol did not additionally influence the lipid bilayer dynamics. Fatty acid spin-labeled SC membranes were treated with the liposome formulations, leading to migration of the spin label to the molecular environment of the formulation and the presence of two spectral components representing distinct mobility states. In terms of molecular dynamics, these environments correspond to the lipid domains of the untreated SC and the liposome, indicating a poor interaction between the liposome and SC membranes. However, the contact was sufficient to allow a pronounced exchange of the spin-labeled fatty acid. Our data suggest that flexible liposomes may access the inner intercellular membranes of the SC and facilitate mutual lipid exchange without losing their relative liposomal integrity.

Effects of ethanol/l-menthol on the dynamics and partitioning of spin-labeled lipids in the stratum corneum.

The interaction of ethanol as well as ethanol/L-menthol mixtures with the uppermost layer of epidermis, the stratum corneum, was investigated by electron paramagnetic resonance (EPR) spectroscopy utilizing spin-labeled analogs of androstanol (ASL), stearic acid (5-DSA) and methyl stearate (5-DMS). The EPR spectra of these spin probes structured in stratum corneum tissue of neonatal rat are characterized by the coexistence of two spectral components indicating the presence of two classes of spin labels with very different states of mobility. Probably, one class of spin labels is H-bonded to the polar surface of the membrane and another class corresponds to spin labels more deeply inserted in the hydrophobic core. EPR results showed that in the ethanol range 0-70% neither fluidity in stratum corneum membranes nor the relative fractions of these two components changes were observed. Instead, ethanol only caused a selective extraction of spin labels. The removal of the steroid ASL began at 30% ethanol, reaching extraction levels over 50% at ethanol concentrations of 60-70%, whereas the more hydrophobic 5-DMS was partially removed only with 70% ethanol. Addition of 5% L-menthol to the solvent containing 20% ethanol increases both the mobility and the fraction of those spin labels situated in the hydrophobic core (more mobile spectral component). Altogether, these findings suggest that the L-menthol stabilizes mainly in the central region of stratum corneum membranes attracting the membrane lipids and causing hydrogen bond ruptures in the polar membrane interface.

Effects of 1,8-cineole on the dynamics of lipids and proteins of stratum corneum.

The interaction of a potent percutaneous penetration enhancer, 1,8-cineole, with the stratum corneum (SC) and DPPC membranes was investigated by electron paramagnetic resonance spectroscopy (EPR) of spin-labeled analogs of stearic acid (5-DSA) and androstanol (ASL). The EPR spectra of lipid derivatives spin probes structured in stratum corneum tissue of neonatal rat containing of 0.1-10% (v/v) 1,8-cineole in the solvent indicate an abrupt increase in membrane fluidity at around 1% 1,8-cineole. These spectra of stratum corneum membranes are characterized by the presence of two spectral components differing in mobility. Component 1 was attributed to the spin labels H-bonded to the headgroups, while component 2 possibly arose from spin labels H-bonded to water molecules or temporally non-hydrogen-bonded. With the addition of 1,8-cineole, the spin probes were transferred from the motionally more restricted component 1 to the more mobile component 2, suggesting that 1,8-cineole causes ruptures in the hydrogen-bonded network of the membrane-water interface, with consequent displacements of spin probes towards the hydrophobic core. 1,8-Cineole increased the rotational diffusion rates of component 2, whereas no significant mobility changes were observed in component 1. The EPR spectra of maleimide derivative spin label (6-MSL) covalently attached to stratum corneum proteins indicate that 1,8-cineole does not alter the dynamics of protein backbones. Instead, this terpene only increases the solvent's ability to 'dissolve' and mobilize the nitroxide side chain, which is in agreement with its low irritation response.

Fatores clínicos e sociodemográficos associados a recuperação da marcha de indivíduos após acidente vascular cerebral trombolisado na fase aguda / Clinical and sociodemographic factors associated with gait recovery in individuals after thrombolysis for acute ischemic stroke

O tratamento trombolítico promove reperfusão cerebral após acidente vascular cerebral (AVC) isquêmico, e é considerado o tratamento mais eficaz na fase aguda, estando associado a melhores desfechos clínicos e funcionais. Entre as principais sequelas após AVC estão a hemiparesia e o déficit de equilíbrio, que repercutem diretamente na locomoção do indivíduo. Objetivo: Investigar quais fatores estão associados com a recuperação da marcha na fase aguda do AVC trombolisado. Métodos: Trata-se de um estudo longitudinal, com 32 indivíduos na fase aguda do AVC trombolisado. Os indivíduos foram avaliados nas primeiras horas após terem sido submetidos à terapia trombolítica, e após 7 dias ou no momento da alta da unidade de internamento. Resultados: O desfecho principal foi a presença ou não de marcha independente até o sétimo dia de internamento ou até a alta da unidade. A variável resposta foi o número de dias necessário para recuperar a marcha, sendo analisada em 3 categorias: "1 dia", "2 dias" e "3 ou mais dias". Dos 32 indivíduos da amostra apenas 4 não andaram em até 7 dias após o AVC e cerca de 50% andou no primeiro dia de internamento. Houve associação significativa entre a Escala de Equilíbrio de Berg e o tempo para andar. Conclusão: O estudo sugere que a maioria dos indivíduos submetidos à trombólise para tratamento de AVC isquêmico recupera a capacidade de andar dentro de sete dias da ocorrência do evento, e que esta recuperação está associada ao equilíbrio nas primeiras horas após o AVC.

The thrombolytic treatment promotes cerebral reperfusion after ischemic stroke and it is considered the most effective treatment in the acute phase. The thrombolysis is associated with better clinical and functional outcomes. Hemiparesis and balance deficits are important sequelae after a stroke and both affect the individual's locomotion. Objective: The aim of this study was to investigate what factors are associated with gait recovery in the acute phase of stroke after thrombolysis. Method: This is a longitudinal study, including 32 individuals in the acute phase of stroke after thrombolytic treatment. The individuals were evaluated in the first hours after thrombolytic therapy, and then, after 7 days or at the time of discharge from the inpatient unit. Results: The main outcome was the presence or absence of independent gait until the seventh day of hospitalization or until discharge from the unit. The response variable was the number of days required to recover gait, being analyzed in 3 categories: "1 day", "2 days" and "3 or more days". Of the 32 individuals in the sample, only 4 did not walk within 7 days after the stroke and about 50% walked on the first day of hospitalization. There was a significant association between the Berg Balance Scale and the time to walk. Conclusions: This study suggests that most individuals undergoing thrombolysis for the treatment of ischemic stroke recover their capacity to walk within seven days of the event and this recovery is associated with balance in the first hours after stroke.