Long-term clinical and histological safety and efficacy of the CO2 laser for treatment of genitourinary syndrome of menopause: an original study.

OBJECTIVE: This study aimed to evaluate histological modifications of the vaginal mucosa after repeated microablative fractional CO2 laser treatments. As secondary objectives we evaluated the clinical effects associated with repeated microablative fractional CO2 laser treatments using validated questionnaires. METHODS: A prospective intervention study was performed in the Division of Gynecology and Obstetrics, Urogynecology Unit, IRCCS San Raffaele Scientific Institute with 15 postmenopausal women complaining of genitourinary syndrome of menopause symptoms. The cohort of patients was submitted to at least two previous laser treatment cycles in the past years. The Vaginal Health Index (VHI), visual analog scale (VAS), Female Sexual Function Index (FSFI), Urinary Distress Inventory-6 (UDI-6), International Consultation on Incontinence Questionnaire - Urinary Incontinence (ICIQ-UI) and 5-point Likert scale were used. Moreover, histological examinations were carried out on all samples. RESULTS: At 4 weeks after the last treatment, the VHI score and all FSFI items were significantly increased compared with baseline. We observed a statistically significant decrease in both frequency and severity for all urinary symptoms after the follow-up. We observed a statistically significant increase in the number of epithelial cell layers with a consequent increase in epithelial thickness, in the number of glycogen-filled cells and in the number of papillae after the laser treatment. No signs of fibrosis were observed as neovascularization was observed in each woman. CONCLUSIONS: This is the first study demonstrating the histological persistency of efficacy in repeated annually laser treatment cycles, with tissue changes always leading to regenerative results without any sign of fibrosis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04868812 (release date: 27 April 2021).

Piezoelectric control of the mobility of a domain wall driven by adiabatic and non-adiabatic torques.

The rich internal degrees of freedom of magnetic domain walls make them an attractive complement to electron charge for exploring new concepts of storage, transport and processing of information. Here we use the tunable internal structure of a domain wall in a perpendicularly magnetized GaMnAsP/GaAs ferromagnetic semiconductor and demonstrate devices in which piezoelectrically controlled magnetic anisotropy yields up to 500% mobility variations for an electrical-current-driven domain wall. We observe current-induced domain wall motion over a wide range of current-pulse amplitudes and report a direct observation and the piezoelectric control of the Walker breakdown separating two regimes with different mobilities. Our work demonstrates that in spin-orbit-coupled ferromagnets with weak extrinsic domain wall pinning, the piezoelectric control allows one to experimentally assess the upper and lower boundaries of the characteristic ratio of adiabatic and non-adiabatic spin-transfer torques in the current-driven domain wall motion.

[Periacetabular osteotomy medium term survival in adult acetabular dysplasia]. / Survie de l'ostéotomie périacétabulaire à moyen terme dans le traitement de la dysplasie acétabulaire de l'adulte.

PURPOSE OF THE STUDY: Acetabular dysplasia is a recognized cause of early onset degenerative hip disease. With the widespread use of arthroplasty, the role for conservative treatment has become a controversial issue. Periacetabular osteotomy (PAO) as proposed by Ganz has several advantages, but remains a technically difficult procedure. The purpose of this work was to assess our mid-term results considering indications and potential complications and to describe changes in our technique. MATERIAL AND METHODS: This study included 33 dysplasic hips in 24 women and four men, treated by PAO. Mean age was 32 years (range 18-47). Mean follow-up was 12 years (range 2-19). The radiographic work-up included an anteroposterior view of the pelvis and anterior and Lequesne oblique views of the hip joint. The cephalocervicodiaphyseal (CC'D), lateral cover (VCE), anterior cover (VCA), and acetabular roof horizontality (HTE) angles and noted whether osteoarthritis was present or not. Hips were classified with the Hip Study Group system as moderate dysplasia (VCE and VCA 25 degrees to 21 degrees ), severe dysplasia (20 degrees to 5 degrees ) and extreme dysplasia (less than 5 degrees ). The complete work-up included an assessment of joint congruency with recentered films in addition to the surgical lateral view of the hip in order to determine a new index called S/FH (S: acetabular surface, FH: half of the femoral head surface). ArthroCT and MRI were performed in patients with signs of osteoarthritis. The original technique included three cuts (ilio-ischiatic, iliopubic, and iliac) close to the acetabulum using a triple access: infracoxofemoral, intrapelvic, and extrapelvic. The first change in the technique was an osteotomy of the anterosuperior iliac spine and an oblique iliac cut farther from the acetabulum. RESULTS: Preoperatively, average angle measurements were as follows: 135 degrees (121 to 150 degrees ) for CC'D, 23.2 degrees (3 degrees to 40 degrees ) for HTE, 7.6 degrees (-14 degrees to 22 degrees ) for VCE, 11.3 degrees (-26 degrees to 32 degrees ) for VCA. Postoperatively, the values were as follows: 134.5 degrees (121 degrees to 150 degrees ) for CC'D, 9.5 degrees (-9 degrees to 20 degrees ) for HTE, 31.7 degrees (14 degrees to 60 degrees ) for VCE and 31.7 degrees (10 degrees to 48 degrees ) for VCA. An intertrochanteric osteotomy was also performed in one patient. The mean Postel-Merle-d'Aubigné score improved from 7.5 points (range 5.6-11) preoperatively to 14.9 (range 8.1-18). At last follow-up, there was no sign of osetoarthritic degradation in 17 patients (51.5%). Seven patients required total hip arthroplasty at mean four years (two to nine years), including one for aseptic acetabular necrosis. Survival was 73.8+/-9 % at 12 years. DISCUSSION AND CONCLUSION: This study confirmed the importance of PAO as part of the therapeutic armamentarium for conservative treatment of acetabular dyplasia. Several changes were made in the original technique: the three cuts were all done via the intrapelvic access; for severe and extreme dysplasia, a two thirds PAO was performed. At the present time, the best indication appears to be young subjects (aged less than 30 years) with moderate to severe dysplasia, with no sign (even minimal) of intra-articular disorder or osteoarthritis.

Evaluation of skin permeability of sesquiterpenes of an innovative supercritical carbon dioxide Arnica extract by HPLC/DAD/MS.

Recently, a supercritical carbon dioxide dried extract of Amica flower, with a very high sesquiterpene content was developed. In view of using this extract in formulations for cutaneous application, the ability of sesquiterpenes to permeate the skin was evaluated by HPLC/DAD/MS using the following permeation enhancers: oleic acid (OA), dimethylsulfoxide (DMSO), lauroglycol, isopropyl myristate and Tween 80. A skin permeation study was performed using a modified Franz diffusion cell and the human stratum corneum and epidermis as membrane. Solutions of the enhancers were directly analysed after dilution with methanol or DMSO. A simple RP-HPLC-DAD-MS method for the quantification of the sesquiterpenes was developed and the method showed no interference with the other substances extracted from the skin and the permeation enhancers. The study evidenced that among the selected skin permeation enhancers, DMSO and OA canbe considered as good candidates to be used in preparations for cutaneous application.

Does gait analysis change clinical decision-making in poststroke patients? Results from a pragmatic prospective observational study.

BACKGROUND: Gait analysis (GA) was demonstrated to change presurgical planning and improve gait outcomes in children with Cerebral Palsy. GA is often used also to assess walking capability of poststroke subjects, although its influence in the clinical management of these patients has not yet been established. OBJECTIVE: To assess the impact of GA on clinical decision-making in adult chronic poststroke patients. DESIGN: Pragmatic prospective observational study. SETTING: Rehabilitation hospital, both outpatients and inpatients. POPULATION: Forty-nine patients (age: 53.3±14.5 years) who had had a cerebrovascular accident 35.2±26.4 months before and were referred to the gait analysis service. METHODS: Recommendations of therapeutic treatments before and after the analysis of GA data were compared, together with the confidence level of recommendations on a 10-point scale. Frequency of changes of post-GA vs pre-GA recommendations were computed for each recommendation type: surgery, botulinum toxin (BT), orthotic management and physiotherapy. RESULTS: Based on the analysis of GA data, 71% of poststroke subjects had their treatment planning changed in some components. Indeed, 73% of patients with indications for surgery had their surgical planning changed; 81%, 37% and 32% had, respectively, their BT, orthotic and physiotherapy planning changed. Confidence level of recommendations increased significantly after GA, in both the whole group of patients (from 6.7±1.4 to 8.7±0.6, P<0.01) and the subgroup whose recommendations had not changed (7.0±1.5 vs. 8.8±0.4, P<0.01). CONCLUSION: GA significantly influences the therapeutic planning and reinforces decision-making for chronic poststroke patients. Further work should be done to better translate GA results into indications for specific physiotherapy. CLINICAL REHABILITATION IMPACT: The use of GA as a tool to better define the rehabilitation planning in post-stroke patients should be fostered, particularly when surgery or botulinum toxin are considered and/or the prescription of orthoses is hypothesised.

Polymethacrylate salts as new low-swellable mucoadhesive materials.

The sodium and potassium salts of the methacrylic copolymers Eudragit L100 and Eudragit S100 were prepared with the aim to develop new low-swellable mucoadhesive materials intended for the preparation of buccal dosage forms. The physico-chemical characterization of the copolymers and the corresponding sodium and potassium salts was performed by using Fourier-transform infrared (FT-IR) spectroscopy and thermal analysis. When ionization occurred, the carboxylic acid group absorption band (1730 cm(-1)) was replaced by another characteristic band at 1560 cm(-1). After salification the T(g) of the two polymers shifted towards higher values and it was not significantly influenced by the contraion nature. The intrinsic dissolution rate at infinite rotation speed (7.354

Development of local patches containing melilot extract and ex vivo-in vivo evaluation of skin permeation.

Melilot extract could be effective in treating localised varicose syndrome or capillary fragility. The monolayer patch was selected to obtain a prolonged release of coumarin contained in the phytocomplex. Two types of methacrylic patches (patch 1 based on a blend of Eudragit E100 and Eudragit NE; patch 2 based on Eudragit L100) were prepared. Both patches were equivalent in terms of coumarin release and ex vivo skin permeation profiles. The two patches differed significantly as regards respective adhesive properties. At low peel rate only patch 1 showed adhesive failure as confirmed by the in vivo performance. When comparing the behaviour of the patches containing melilot extract with analogous patches containing synthetic coumarin, no melilot phytocomplex enhancer effect was shown. The data of the ex vivo coumarin skin permeation and those obtained by the in vivo stripping technique showed a good correlation (r(2)=0.9727 for patch 1, r(2)=0.9835 for patch 2).

In vitro skin permeation of Sinitrodil, a member of a new class of nitrovasodilator drugs.

Clinical trials have shown the potential of benzoxazinones, a new class of organic nitrates, in cardiovascular therapy. In particular Sinitrodil possesses a coronary vascular selectivity greater than that of Nitroglycerin and isosorbide dinitrate. The objective of this study was a preliminary evaluation of the ability of these new organic nitrate derivatives to reach therapeutical steady-state plasma concentrations following a transdermal administration. In vitro permeation studies through human stratum corneum and epidermis have been conducted on two members of this class: Sinitrodil (ITF 296) and ITF 1129. Comparative studies have also been carried out with Nitroglycerin, Isosorbide dinitrate and Nicorandil. Two different fixed concentrations were tested: 0.08% w/v solution and saturated solution. Sinitrodil could be considered a good candidate for transdermal administration on the basis of the in vitro permeation results and of the known therapeutical plasma concentration.

Characterization of nifedipine solid dispersions.

The sublingual administration of nifedipine (NIF) is currently used in clinical practice. The sublingual administration of NIF solid dispersions (SD), by using a suitable dispenser, appears an interesting approach in the treatment of moderate and severe hypertensive emergencies. With this aim nine SD made of NIF and a low viscosity hydroxypropylmethylcellulose (HPMC) in different ratio were prepared by means of spray-drying technique and their structure was studied. Moreover, the drug dissolution properties from SD were verified. The characteristic peaks of crystalline NIF were not detectable by using the X-ray analysis when the NIF/HPMC ratios were lower than 50/50 w/w. In thermograms obtained from SD, the NIF melting endothermic peak disappeared when NIF/HPMC ratios were lower than 30/70 w/w; the experimental Tg values of SD were lower than the Tg values predicted by Gordon Taylor equation suggesting some type of non-ideality of mixing. In the SD FTIR spectra the NH stretching vibrations and the C=O stretch in esteric groups of NIF shift to free NH and C=O regions indicating the rupture of intermolecular hydrogen bond in the crystalline structure of NIF. The prepared SD improved the NIF dissolution rate in comparison with that of commercial NIF or NIF/HPMC physical mixtures. Moreover, the concentration of NIF in the dissolution medium increased decreasing the NIF content.

Application of viscometry and solubility parameters in miconazole patches development.

Nine binary mixtures of seven different methacrylic copolymer systems (Plastoid((R)) E 35 L (PLE) and Plastoid((R)) L 50 (PLL); Eudragit((R)) (Eu) NE, RL, RS, L, S) were tested as components of monolayer patches containing miconazole. Only three mixtures (PLE:EuNE, PLE:EuRL and PLE:EuRS) were suitable for the preparation of placebo matrices. Miconazole patches with good technological characteristics were obtained by using mixtures of PLE:EuNE and PLE:EuRL. The in vitro miconazole release rate from the two patches and from the patch prepared using only PLE were significantly different. The amounts of drug released in 24 h were quite satisfactory. A mathematical model based on capillary viscometry data was used for the evaluation of interactions between copolymers. This was useful to predict and understand the mechanisms related to the instability of the prepared mixture. The solubility parameters of the drug and of the matrix were also calculated. Miconazole release was faster when the difference between the solubility parameters of the matrix and of the drug was higher. A relationship between miconazole release rate and the difference of drug and matrix solubility parameters was found. Therefore, the solubility parameter could be applied in formulation studies of patches.

Comparison of different membranes with cultures of keratinocytes from man for percutaneous absorption of nitroglycerine.

The permeability barrier function of cell-culture membranes to the permeation of nitroglycerine was evaluated to find an alternative to skin from man for ex-vivo skin-permeation tests. The membranes were prepared, under submerged conditions, by inducing the growth of keratinocytes, from different donors, on a film of esterified jaluronic acid for different times (10, 20 and 30 days). Their permeability barrier functions were compared with those of some of the most widely used artificial membranes, silicone rubber (Silastic), cellulosic material (Cuprophan, Millipore HAWP), polysulphone membrane (Supor) and polytetrafluoroethylene membrane (TF-PTFE), and with those of biological membranes such as fresh and frozen skin, stratum corneum and epidermis from man, and hairless mouse skin. For each membrane the permeation profile was obtained and the flux was calculated. The permeation profiles for nitroglycerine were similar and linear in the first 2-3 h for all the synthetic membranes tested except TF-PTFE. For this membrane the profile was linear throughout the period considered and the amount permeating in 24 h (1603 microg cm(-2)) was significantly lower than those obtained for the other artificial membranes (between 1926 and 2508 microg cm(-2)). The amounts permeating through all the biological membranes in 24 h were in the range 520 to 781 microg cm(-2), except those for the keratinocyte-culture membranes, which were in the range 1730 to 2553 microg cm(-2). Prolonging the growth period of cultured keratinocytes did not affect nitroglycerine permeation. The findings suggest that these keratinocyte-culture membranes have some advantages--good reproducibility if obtained from the same donor; many membranes can be obtained from the same donor; the preparation is simple; they can be handled more easily than traditional cell-culture membranes; and they afford constant penetration rates for a longer period than synthetic membranes. The membranes could be used for preliminary in-vitro permeation studies.

Solvation enthalpies as descriptors of structure--in vitro percutaneous permeation relationship of benzoxazinones regioisomers.

The aim of this work was to correlate the in vitro human skin permeability, expressed as the permeability coefficient (Kp), and some physicochemical parameters of a new series of benzoxazinones. The in vitro human skin permeability of 14 substances, including regioisomers with CH3, OH, OCH3, and Cl groups in different positions on the aromatic ring, was determined. The modified Franz diffusion cell method was used. The Kp values were in the range 0.14-8.24 cm/h, showing a strong dependence on the position and type of substituent. Physicochemical descriptors usually referred in literature, such as log P, molecular weight and volume (MV), hydrogen bond donor (Hd) and acceptor activity (Ha), and molecular refractivity were considered, with the addition of solvation enthalpy (delta deltaHsolv). Delta deltaHsolv is defined as the difference between formation enthalpies in water and octanol. The algorithm with the best correlation between Kp and physicochemical descriptors was calculated, taking into account the differences observed among the regioisomers. The algorithm obtained with delta deltaHsolv had a good correlation (r2 = 0.749, F = 16.43, P = 0.0005), comparable with the equation, proposed by Potts and Guy, based on MV, Hd and Ha (r2 = 0.830, F = 16.3, P = 0.0004).

Low molecular weight hyaluronic acid prevents oxygen free radical damage to granulation tissue during wound healing.

Hyaluronic acid protects granulation tissue from oxygen free radical damage and stimulates wound healing, but its molecular weight prevents it from permeating the epidermal barrier A low molecular weight hyaluronic acid preparation is able to permeate the skin, but it is unknown whether or not it retains the scavenging effects of oxygen free radicals in granulation tissue. Our experiments were conducted in rats with excisional or incisional wounds. Wound contraction over 11 days and breaking strength on the fifth day were measured. Oxygen free radical production was induced by intraperitoneal administration of two different xenobiotics: phenazine methosulfate and zymosan. The wounds were treated topically with low molecular weight hyaluronic acid (0.2%) cream or placebo. In the incisional wound group, the effects of superoxide dismutase were also determined. Absolute controls received wounds and placebo but no xenobiotics. Wound healing was significantly slower in the xenobiotic group than in the control groups. These effects were strongly reduced by topical administration of low molecular weight hyaluronic acid (0.2%) cream and in incisional wounds by topically injected superoxide dismutase. Low molecular weight hyaluronic acid is effective as the native compound against oxygen free radicals. Its pharmacological effects through transdermal administration should be tested in appropriate models.

Effect of blood letting on serum aminotransferase levels of patients with chronic hepatitis C and iron overload.

OBJECTIVE: To confirm the existing evidence that blood letting reduces serum aminotransferase levels and to seek factors associated with a greater reduction in subjects with chronic hepatitis C and iron overload. DESIGN: Prospective, open label, non controlled study in two northern Italian hospitals. PATIENTS: Sixteen patients with histologically proven chronic hepatitis, positive hepatitis C virus serology, HCV-RNA detectable in their sera, and histological and biochemical signs of iron overload, nonresponders to interferon alpha therapy, underwent weekly phlebotomies until serum ferritin values < or = 50 ng/mL were obtained. Serum aminotransferases, serum ferritin and transferrin saturation were then measured and compared with values at baseline. RESULTS: Alanine aminotransferase and aspartate aminotransferase levels fell after phlebotomies from 193 +/- 107 IU/L to 115 +/- 53 IU/L (t = 4.94, p = 0.0001) and from 124 +/- 60 IU/L to 85 +/- 35 IU/L (t = 3.76, p = 0.002), respectively. The magnitude of the reduction correlated with baseline aminotransferase levels (r = 0.68, p = 0.004 for alanine aminotransferase and r = 0.63, p = 0.009 for aspartate aminotransferase), but not with those of serum ferritin and transferrin saturation percentage, nor with the quantity of iron removed. There was a trend towards a greater alanine aminotransferase reduction in patients with the highest baseline serum ferritin (r = 0.26, p = 0.14). CONCLUSIONS: Blood letting was effective in reducing serum aminotransferase levels of patients with chronic hepatitis C and iron overload, especially those with the highest baseline aminotransferase levels.

Evaluation of adhesive properties of transdermal therapeutic systems containing nitroglycerin.

The patch performances and the success of the transdermal drug delivery can be significantly affected by the quality of contact between the patch and the skin. Poor adhesion will dramatically reduce percutaneous delivery. In this study the adhesive properties (peel force and creep resistance) of three monolayer self-adhesive nitroglycerin (NTG) patches available on the market, Deponit, Minitran, and Triniplas, were compared. The patches were characterized also in terms of in vitro drug release and ex vivo skin permeation. The creep resistance values verified in the case of Deponit and Triniplas indicated a low cohesion of these matrices. The peel force values were in the accepted range, even if Triniplas and Deponit showed values double that shown by Minitran. The percentage of NTG released in vitro after two hours in all cases exceeded ninety percent. The ex vivo permeation profiles were similar, even if the three patches had different loaded amounts and surface areas. The measured permeated amount, 11 mg permeated in 24 h, was predictive of the claimed in vivo release (10 mg in 24 h).

Is propranolol compounding from tablet safe for pediatric use? Results from an experimental test.

AIM: Although propranolol is widely used in the treatment of infantile hemangiomas, the standard 40 mg tablet needs to be fractioned to obtain 10 mg parts, with even lower doses (i.e., 2-3 mg/kg/day divided into 2-3 daily doses) required in infants. This study evaluated the weight and dose uniformity in split quarters of propranolol tablets. METHODS: Twenty pharmacy students split 70 propranolol tablets by using a kitchen knife in order to obtain 200 quarters, which were considered integral and adequate for administration. Intact tablets and quarters were weighed. The content of propranolol in tablet quarters was determined on 200 quarters by using high performance liquid chromatography. RESULTS: Overall, 265 parts (94.6%) were integral and 213 (76.1%) were considered as adequate for administration. The mean (± standard deviation) weight of quarters judged as suitable and non-suitable for administration was 49.56 ± 5.27 mg and 46.24 ± 7.53 mg, respectively. Splitting caused a mean weight loss in each tablet of 2.97 ± 2.91 mg (median 2.06 mg). The percentage of quarters with weight lower than theoretical was 55.88%, and the remaining weighted more than expected. The mean propranolol content in quarters was 9.52 ± 0.96 mg (median 9.42 mg, range 7.36-12.23 mg) and 42% of quarters were out of the ± 10% acceptance range. CONCLUSION: The manual splitting of propranolol 40 mg tablets produced a significant proportion of quarters not suitable for administration in children or with a weight and/or an active concentration outside of the required range. The availability of a pediatric oral solution of propranolol will reduce the risk of incorrect dosing.

Myoelectrically driven functional electrical stimulation may increase motor recovery of upper limb in poststroke subjects: a randomized controlled pilot study.

The objective of this randomized controlled pilot study was to assess the feasibility and effectiveness of myoelectrically controlled functional electrical stimulation (MeCFES) for rehabilitation of the upper limb in poststroke subjects. Eleven poststroke hemiparetic subjects with residual proximal control of the arm, but impaired volitional opening of the paretic hand, were enrolled and randomized into a treated and a control group. Subjects received 3 to 5 treatment sessions per week until totaling 25 sessions. In the experimental group, myoelectric activity from wrist and finger extensors was used to control stimulation of the same muscles. Patients treated with MeCFES (n = 5) had a significant (p = 0.04) and clinically important improvement in Action Research Arm Test score (median change 9 points), confirmed by an Individually Prioritized Problem Assessment self-evaluation score. This improvement was maintained at follow-up. The control group did not show a significant improvement (p = 0.13). The reduced sample size of participants, together with confounding factors such as spontaneous recovery, calls for larger studies to draw definite conclusions. However, the large and persistent treatment effect seen in our results indicate that MeCFES could play an important role as a clinical tool for stroke rehabilitation.

Spin-orbit-driven ferromagnetic resonance.

Ferromagnetic resonance is the most widely used technique for characterizing ferromagnetic materials. However, its use is generally restricted to wafer-scale samples or specific micro-magnetic devices, such as spin valves, which have a spatially varying magnetization profile and where ferromagnetic resonance can be induced by an alternating current owing to angular momentum transfer. Here we introduce a form of ferromagnetic resonance in which an electric current oscillating at microwave frequencies is used to create an effective magnetic field in the magnetic material being probed, which makes it possible to characterize individual nanoscale samples with uniform magnetization profiles. The technique takes advantage of the microscopic non-collinearity of individual electron spins arising from spin-orbit coupling and bulk or structural inversion asymmetry in the band structure of the sample. We characterize lithographically patterned (Ga,Mn)As and (Ga,Mn)(As,P) nanoscale bars, including broadband measurements of resonant damping as a function of frequency, and measurements of anisotropy as a function of bar width and strain. In addition, vector magnetometry on the driving fields reveals contributions with the symmetry of both the Dresselhaus and Rashba spin-orbit interactions.

Effect of drug chirality on the skin permeability of ibuprofen.

The in vitro passive diffusion of S-ibuprofen (S-IB) and RS-ibuprofen (RS-IB) through human epidermis was determined to study the effects of drug chirality. S-IB has a lower melting point (T(m)=54 degrees C) than RS-IB (T(m)=77 degrees C) and, therefore, a greater solubility (S-IB: 127+/-1 microg/mL; RS-IB: 81+/-1 microg/mL). Supersaturated plasters were prepared by using a poly(dimethylsiloxane) adhesive and Eugragit RL and propylene glycol as antinucleant agents. The in vitro skin permeation profiles were determined by Franz cells and human epidermis obtained from three different donors. The permeation profiles of S-IB from saturated solutions resulted statistically higher than those of RS-IB (p<0.002). When plasters were used, no differences were noticeable between the enantiomer and racemate (p>0.17). The latter unexpected results could be explained considering that the RS-IB or S-IB in vitro release rate constants, determined using 3% w/w or 6% w/w loaded plasters, were not statistically different, suggesting that the drug diffusivity within the adhesive matrix represented the rate limiting step to the skin absorption.

Functional resources to increase gait speed in people with stroke: strategies adopted compared to healthy controls.

Thirty-nine adult individuals with stroke in the stable phase were asked to walk at their preferred speed and then as fast as possible. A set of gait indexes were computed, including spatial temporal parameters, ankle and hip mechanical work, and timing of ankle push-off onset, for comparison with normal velocity-dependent profiles. Algorithms were used to classify the resulting gait patterns when the patients walked at their preferred speed and fast and to identify the patients' strategies to maximise speed. Patients' strategies were characterised by a variation in the parameters, which were reduced, equal or increased, in relation to normal patterns. At both speeds, stroke individuals tended to walk at higher cadence and with shorter stride length. At the preferred speed the investigated parameters for all patients were mostly within the normal profile (71.8-94.9%). The exception was the finding of positive work at the ankle where 64% of the stroke individuals showed reduced work production. At fast speed (increments to 36%BH/s) fewer patients presented values within the normal profile for all the parameters (17.9-74.4%), with the exception of negative work at the ankle and hip. The parameter variations showed a more consistently abnormal picture. The results indicate that, in order to increase gait speed, patients with hemiparesis have different functional resources on which to draw, and these vary from individual to individual. Thus, gait analysis at different gait speed should be adopted to develop individualised programs that will improve quality of life for the patients.