Is bladder outlet obstruction responsible for a successful surgical outcome in women with complicated stress urinary incontinence? Urodynamic results before and after a Remeex® readjustable sling.

AIMS: To describe the changes in urodynamic parameters after Remeex® placement in women with recurrent stress urinary incontinence (rSUI) or intrinsic sphincteric deficiency (ISD) and to analyze a potential relationship between postoperative bladder outlet obstruction and a successful surgical outcome. METHODS: Retrospective analysis of those women who had undergone Remeex® placement due to rSUI or ISD in our department between 2000 and 2017. All patients underwent urodynamic evaluation before and after the surgery. If tension readjustment was required, postoperative urodynamics was performed after the last regulation, once the final continence status had been achieved. The female Bladder Outlet Obstruction Index (BOOIf) was calculated for all patients postoperatively. Obstruction was considered present if BOOIf was >18. Pre- and postoperative urodynamic variables were compared. Postoperative urodynamic changes were also compared between cured and noncured patients. RESULTS: A total of 205 women were included. After a follow-up of 89 ± 36 months, 165 women (80.5%) were continent. A significant impairment in the majority of the urodynamic parameters was observed. Mean postoperative BOOIf was -11.8 ± 21.5 in cured patients and -15.3 ± 23.1 in noncured patients (p = 0.365); 15 (9.1%) patients in the cured group had a postoperative BOOIf >18, whereas all (100%) patients in the noncured group had a postoperative BOOIf <18. CONCLUSIONS: Most urodynamic parameters may worsen after the Remeex® system placement. Postoperative urodynamic parameters may not differ substantially between cured and noncured patients, although a certain grade of bladder outlet obstruction could be related to postoperative continence status in some patients.

The relationship between calcium oxalate lithiasis and chronic proinflammatory intestinal dysbiosis pattern: a prospective study.

The objective is to establish whether a pattern of intestinal dysbiosis exists in calcium oxalate (CaOx) lithiasis and, if so, to identify its characteristics and explore whether there are differences in the pattern between CaOx dihydrate (COD) and monohydrate (COM) lithiasis. With this aim 24 patients diagnosed with CaOx lithiasis by means of optical microscopy and spectrometry were prospectively recruited. Faecal analysis was carried out by means of RT-PCR 16S rRNA assay and agar plate culture according to the methodology proposed by the Institute of Microecology (Herborn, Germany). The total number of bacteria was depleted due to COD lithiasis (p = 0.036). The mean values of immunoregulating microbiota were normal, but the percentage of normal values was lower in the COD group (30%) than in the COM group (69.2%) (p = 0.062). The total mean values of protective microbiota were normal in both groups. There was a large decrease in the mean values of the muconutritive microbiota Akkermansia muciniphila and Faecalibacterium prausnitzii, the most intense decline being observed in the COD group (p = 0.019). Levels of proteolytic microbiota were elevated in both groups, without differences between them. We conclude that patients with CaOx lithiasis have a chronic pro-inflammatory intestinal dysbiosis pattern characterised by a reduction in the total number of bacteria, a reduction in immunoregulating microbiota and a large reduction in muconutritive microbiota that is significantly more intense in COD lithiasis than in COM lithiasis.

Treatment Response and Complications after Intradetrusor OnabotulinumtoxinA Injection in Male Patients with Idiopathic Overactive Bladder Syndrome.

PURPOSE: We sought to assess the treatment response, complications and treatment continuation after onabotulinumtoxinA injection in male patients. MATERIALS AND METHODS: We performed a retrospective study of men with refractory idiopathic overactive bladder treated with intradetrusor injection of 100 IU onabotulinumtoxinA since 2007 in our department. Patients with previous radical prostatectomy were excluded from analysis. The treatment response was assessed using a treatment benefit scale of 1-greatly improved, 2-improved, 3-not changed and 4-worse after treatment. A treatment benefit scale score of 1 or 2 was considered a treatment response. Complications were classified according to the CD (Clavien-Dindo) classification. Treatment was considered to have continued if at the last visit patients had received an onabotulinumtoxinA injection within the preceding 12 months. We performed univariate and multivariate analyses to assess factors predictive of the treatment response, complications and continuation on treatment. RESULTS: Of the 146 men with a mean ± SD age of 70.1 ± 13.3 years who were included in study 91 (62.3%) reported a response to treatment. A total of 24 complications (16.4%) were detected, including 19 cases (13%) of urinary retention (CD 2), 2 (1.3%) of hematuria (CD 1) and 3 (2%) of urinary infection (CD 2). Followup was more than 12 months in 128 patients, of whom 88 (68.8%) had discontinued treatment by the end of followup. A higher bladder outlet obstruction index was the only factor predicting a lower treatment response rate and a higher complication rate. CONCLUSIONS: Most male patients with idiopathic overactive bladder showed a treatment response after intradetrusor onabotulinumtoxinA injection. However, the majority discontinued treatment. A higher bladder outlet obstruction index was related to a lower treatment response and a higher complication rate.

In vitro and in vivo Virulence Potential of the Emergent Species of the Acinetobacter baumannii (Ab) Group.

The increased use of molecular identification methods and mass spectrometry has revealed that Acinetobacter spp. of the A. baumannii (Ab) group other than A. baumannii are increasingly being recovered from human samples and may pose a health challenge if neglected. In this study 76 isolates of 5 species within the Ab group (A. baumannii n = 16, A. lactucae n = 12, A. nosocomialis n = 16, A. pittii n = 20, and A. seifertii n = 12), were compared in terms of antimicrobial susceptibility, carriage of intrinsic resistance genes, biofilm formation, and the ability to kill Caenorhabditis elegans in an infection assay. In agreement with previous studies, antimicrobial resistance was common among A. baumannii while all other species were generally more susceptible. Carriage of genes encoding different efflux pumps was frequent in all species and the presence of intrinsic class D ß-lactamases was reported in A. baumannii, A. lactucae (heterotypic synonym of A. dijkshoorniae) and A. pittii but not in A. nosocomialis and A. seifertii. A. baumannii and A. nosocomialis presented weaker pathogenicity in our in vitro and in vivo models than A. seifertii, A. pittii and, especially, A. lactucae. Isolates from the former species showed decreased biofilm formation and required a longer time to kill C. elegans nematodes. These results suggest relevant differences in terms of antibiotic susceptibility patterns among the members of the Ab group as well as highlight a higher pathogenicity potential for the emerging species of the group in this particular model. Nevertheless, the impact of such potential in the human host still remains to be determined.

Skin delivery of antioxidant surfactants based on gallic acid and hydroxytyrosol.

OBJECTIVES: The aim of this study has been to investigate the dermal absorption profile of the antioxidant compounds gallic acid and hydroxytyrosol as well as their derivatives, hexanoate (hexyl gallate and hydroxytyrosol hexanoate) and octanoate (octyl gallate and octanoate derivative) alkyl esters (antioxidant surfactants). Previously, the scavenging capacity of these compounds, expressed as efficient dose ED50, has also determined. METHODS: The percutaneous absorption of these compounds was obtained by an in vitro methodology using porcine skin biopsies on Franz static diffusion cells. The antiradical activity of compounds was determined using the 1,1-diphenyl-2-picrylhydrazyl free radical method. KEY FINDINGS: The percutaneous penetration results show the presence of antioxidants in all layers of the skin. The content of the cutaneously absorbed compound is higher for the antioxidant surfactants (ester derivatives). This particular behaviour could be due to the higher hydrophobicity of these compounds and the presence of surface activity in the antioxidant surfactants. CONCLUSIONS: These new antioxidant surfactants display optimum properties, which may be useful in the preparation of emulsified systems in cosmetic and pharmaceutical formulations because of their suitable surface activity and because they can protect the skin from oxidative damage.

Antioxidative effects and percutaneous absorption of five polyphenols.

A new strategy was designed to evaluate the antioxidant effectiveness of five topically applied polyphenols following skin penetration profiles. The antioxidants were the following polyphenol derivatives: epicatechin, resveratrol, rutin, quercetin, and trolox, which was used as the reference antioxidant. The hydrophilic/lipophilic character of these compounds was evaluated, and their antioxidant activity was measured by the DPPH method. The percutaneous absorption of these polyphenols was obtained by an in vitro methodology using porcine skin biopsies. This methodology involves the quantification of the antioxidants present in each specific skin layer to evaluate antioxidant effectiveness. The antioxidant activity in each skin layer was also determined by the DPPH method. The results indicated that lipophilic antioxidants (epicatechin, resveratrol, quercetin, and trolox) penetrated deeper into the skin layers, whereas a more hydrophilic compound, rutin, remained on the skin surface. The antioxidant evaluation of each skin compartment suggested that resveratrol and rutin were the most effective topically applied compounds in view of their antioxidant activity and their skin penetration profile.

Characterization of new DOPC/DHPC platform for dermal applications.

Systems formed by mixtures of the phospholipids dioleoylphosphatidylcholine (DOPC) and dihexanoylphosphatidylcholine (DHPC) were characterized by use of differential scanning calorimetry, small angle X-ray scattering and two electron-microscopy techniques, freeze fracture electron microscopy and cryogenic transmission electron microscopy. These techniques allowed for the determination of the size, morphology, structural topology, self-assembly and thermotropic behavior of the nanostructures present in the mixtures. The interaction between the two phospholipids provides curvatures, irregularities and the increase of thickness and flexibility in the membrane. These effects led to the formation of different aggregates with a differential distribution of both phospholipids. The effect of these systems on the skin in vivo was evaluated by measurement of the biophysical skin parameters. Our results show that the DOPC/DHPC application induces a decrease in the permeability and in the hydration of the tissue. These effects in vivo are related to different microstructural changes promoted by these systems in the skin in vitro, published in a recent work. The fundamental biophysical analyses of DOPC/DHPC systems contribute to our understanding of the mechanisms that govern their interaction with the skin.

Antioxidant cosmeto-textiles: skin assessment.

Resveratrol, a natural product, has been reported to have antioxidant activities such as the scavenging of free radicals. This compound could be used in the dermocosmetic field to protect the skin from oxidative stress. In this work, the percutaneous profile of resveratrol in ethanol solutions through pig skin was determinated by an in vitro methodology. The percutaneous absorption of resveratrol was measured and compared with trolox, an analogous of Vitamin E. Both antioxidants were found in all skin sections (stratum corneum, epidermis, and dermis). Besides, the free radical scavenging activity of resveratrol and trolox has been evaluated using DPPH method. The effective dose (ED50) of compounds and DPPH radical inhibition in each skin layer were evaluated. Under the conditions used for these experiments, it can be deduced that resveratrol is more efficient than trolox as an antioxidant, also in the inner skin layers. The cosmeto-textiles with an active substance incorporated into their structure are increasingly used in the cosmetics and pharmaceutical industries. The action of several cosmeto-textiles on the skin was assessed by in vitro and in vivo methodologies. Samples of these cosmeto-textiles were prepared with resveratrol incorporated into cotton and polyamide fabrics. An in vitro percutaneous absorption was used to demonstrate the delivery of the resveratrol from the textile to the different skin layers (stratum corneum, epidermis, and dermis). Additionally, these cosmeto-textiles containing the antioxidant were applied onto the forearms of volunteers to evaluate the textiles' efficacy in skin penetration. The antioxidant's antiradical capacity was evaluated using the DPPH method. Results showed that resveratrol could be detected in the dermis, epidermis, and stratum corneum (SC) by an in vitro percutaneous absorption method and was also detected in the outermost layers of the SC by an in vivo method (stripping). A smaller amount of resveratrol was penetrated through the skin layers when cosmeto-textiles were used compared to direct topical application of the antioxidant solution. The cosmeto-textiles investigated can act as a reservoir system capable of progressively deliver the active substance to the skin layers. From the skin penetration profiles and the antioxidant efficacy assessment of resveratrol, it is possible to ameliorate the inherent antioxidant capacity of skin.

Bicellar systems to modify the phase behaviour of skin stratum corneum lipids.

Bicellar systems are a fascinating category of versatile lipid assemblies that comprise bilayered disk-shaped nanoaggregates formed in water by long and short alkyl chain phospholipids. Bicelles bridge the gap between micelles and lipid vesicles by combining the attractive properties of both systems. These structures have recently been proposed in dermatological, cosmetic and pharmaceutical applications. Two new binary bicellar systems composed of cholesterol sulphate (SCHOL) and long-chain phospholipids (dimyristoyl-phosphatidylcholine, DMPC, or dipalmitoyl-phosphatidylcholine, DPPC) are characterised herein by differential scanning calorimetry, fluorescence spectroscopy, X-ray scattering and microscopy. Additionally, a comparative study on skin treated with the new SCHOL systems (DMPC/SCHOL and DPPC/SCHOL) and classic DHPC systems (DMPC/DHPC and DPPC/DHPC) was performed. These studies were conducted to determinate how deeply bicelles penetrate into the skin and the extension of their effect on the phase behaviour of stratum corneum (SC) lipids using attenuated total reflectance-Fourier transform infrared spectroscopy and two-photon excitation fluorescence microscopy. Our results show that SCHOL modified the typical discoidal morphology and the phase behaviour of the systems, inducing coexistence of two phases, liquid-ordered and ripple phases. The effect of the systems on SC lipids depends on their composition and is related to the fluidity of the SC lipid alkyl chains. Thus, systems with DMPC induced more disorder in SC lipids than systems with DPPC, and SCHOL did not modify the lipid arrangement. Perdeuterated systems in the infrared spectroscopy technique supported a different distribution in the tissue for every system. DMPC systems were primarily at the first layers of the SC, whereas DPPC systems were more widely distributed. Systems with SCHOL had enhanced distribution and penetration of bicellar systems throughout the SC.

A unique bicellar nanosystem combining two effects on stratum corneum lipids.

In this work a new composition (dioleylphosphatidylcholine, DOPC, and dihexanoylphosphocholine, DHPC) is used to form the bicellar system and to evaluate their effect on stratum corneum (SC) lipids. Through this article, "bicellar system" will refer to a lipid binary system in which lipids are self-assembled forming different nanostructures. DOPC/DHPC system is characterized by dynamic light scattering and cryo-transmission electron microscopy showing two different nanostructures: unilamellar vesicles and tubular structures. In order to study the SC lipid organization attenuated total reflectance Fourier transform infrared spectroscopy, freeze-substitution applied to transmission electron microscopy and X-ray scattering are used. This work compares for the first time the use of two different X-ray scattering methods, transmission with synchrotron radiation and grazing incidence with conventional source, for skin studies. Our results indicate that vesicle-shaped structures remain adhered to the SC surface being unable to penetrate into the skin probably due to their large and voluminous size, while a proportion of structures could have interaction with SC lipids increasing the lamellar organization. Thus, the different nanostructures present in the system have different effects on SC lipids. The appropriate combination of both effects and the possibility to incorporate drugs offer a range of possibilities for the DOPC/DHPC system in development for skin care products.

Bicelles: lipid nanostructured platforms with potential dermal applications.

Bicelles emerge as promising membrane models, and because of their attractive combination of lipid composition, small size and morphological versatility, they become new targets in skin research. Bicelles are able to modify skin biophysical parameters and modulate the skin's barrier function, acting to enhance drug penetration. Because of their nanostructured assemblies, bicelles have the ability to penetrate through the narrow intercellular spaces of the stratum corneum of the skin to reinforce its lipid lamellae. The bicelle structure also allows for the incorporation of different molecules that can be carried through the skin layers. All of these characteristics can be modulated by varying the lipid composition and experimental conditions. The remarkable versatility of bicelles is their most important characteristic, which makes their use possible in various fields. This system represents a platform for dermal applications. In this review, an overview of the main properties of bicelles and their effects on the skin are presented.

Biofunctional textiles prepared with liposomes: in vivo and in vitro assessment.

A sun filter, ethyl hexyl methoxycinnamate (EHMC) used as a tracer, was vehiculized by liposomes made up of internal wool lipids (IWL) or phosphatidylcholine (PC) and applied onto cotton and polyamide fabrics by exhaustion treatments. After topical applications of textiles on human volunteers, skin properties were evaluated by non-invasive biophysical techniques. Two methodologies based on percutaneous absorption were used to determine the content of the active principle penetration into the skin. PC liposomes showed more affinity for the fabric than IWL liposomes. Moreover, polyamide fabrics absorbed a slightly higher percentage of liposomes than cotton fabrics. A significantly higher amount of EHMC skin penetration was found when the biofunctional textiles were topically applied than when formulations were applied onto the skin. Moreover, the polyamide was the fibre with the highest released properties in all cases.

Barrier function of intact and impaired skin: percutaneous penetration of caffeine and salicylic acid.

BACKGROUND: Normally, percutaneous absorption tests are carried out using skin biopsies for an apparent and acceptable physiological condition. However, under different pathological conditions, the stratum corneum (SC) barrier function is impaired. METHODS: The barrier function of the SC was assessed by correlation between the number of repeated applications of tape strips on the skin and its transepidermal water loss (TEWL), as well as by in vitro percutaneous absorption studies of different compounds, using Franz diffusion cells and porcine skin previously stripped. RESULTS: A progressive diminution of the skin barrier function has been detected by TEWL both in vitro and in vivo as the number of skin tape strips increases. On the other hand, the percutaneous absorption of the compounds tested increases in a different way as the number of strips increases. Salicylic acid increases linearly depending on the barrier disturbance. However, percutaneous absorption of caffeine exponentially increased with barrier disturbance. Our results indicate that the barrier impairment of skin always increases the penetration behavior of a given compound; however, the hydrophilic-lipophilic balance of the compounds or formulations used could greatly modify its penetration profile, especially when a modified skin is used. CONCLUSIONS: This in vitro protocol may be useful to simulate the percutaneous absorption profile of some drugs applied onto skin with an impaired SC barrier function and could be used to avoid, to some extent, the use of in vivo experimental animal models in the dermopharmaceutical field.

Bicosomes: bicelles in dilute systems.

Bicelles are discoidal phospholipid nanostructures at high lipid concentrations. Under dilute conditions, bicelles become larger and adopt a variety of morphologies. This work proposes a strategy to preserve the discoidal morphology of bicelles in environments with high water content. Bicelles were formed in concentrated conditions and subsequently encapsulated in liposomes. Later dilution of these new structures, called bicosomes, demonstrated that lipid vesicles were able to isolate and protect bicelles entrapped inside them from the medium. Characterization of systems before and after dilution by dynamic light-scattering spectroscopy and cryo-transmission electron microscopy showed that free bicelles changed in size and morphology, whereas encapsulated bicelles remained unaltered by the effect of dilution. Free and entrapped bicelles (containing the paramagnetic contrast agent gadodiamide) were injected into rat brain lateral ventricles. Coronal and sagittal visualization was performed by magnetic resonance imaging. Whereas rats injected with free bicelles did not survive the surgery, those injected with bicosomes did, and a hyperintensity effect due to gadodiamide was observed in the cerebrospinal fluid. These results indicate that bicosomes are a good means of preserving the morphology of bicelles under dilution conditions.

Application of bicellar systems on skin: diffusion and molecular organization effects.

The effect of bicelles formed by dipalmitoylphosphatidylcholine (DPPC)/dihexanoylphosphatidylcholine (DHPC) on stratum corneum (SC) lipids was studied by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy at different temperatures. Analysis of the lipid organization in terms of chain conformational order and lateral packing shows that the use of bicelles hampers the fluidification of SC lipids with temperature and leads to a lateral packing corresponding to a stable hexagonal phase. Grazing incidence small- and wide-angle X-ray scattering (GISAXS and GIWAXS) techniques confirm these results and give evidence of higher lamellar order after treatment with these bicelles. Additionally, the effects of DPPC/DHPC and dimyristoylphosphatidylcholine (DMPC)/DHPC bicelles at different SC depths were compared. The combination of ATR-FTIR spectroscopy and the tape-stripping method was very useful for this purpose.

Conformational changes in stratum corneum lipids by effect of bicellar systems.

Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy was applied to study the effects of the bicelles formed by dimyristoyl-glycero-phosphocholine (DMPC) and dihexanoyl-glycero-phosphocholine (DHPC) in porcine stratum corneum (SC) in vitro. A comparison of skin samples treated and untreated with bicelles at different temperatures was carried out. The analysis of variations after treatment in the position of the symmetric CH2 stretching, CH2 scissoring, and CH2 rocking vibrations reported important information about the effect of bicelles on the skin. Bicellar systems caused a phase transition from the gel or solid state to the liquid crystalline state in the lipid conformation of SC, reflecting the major order-disorder transition from hexagonally packed to disordered chains. Grazing incidence small and wide X-ray scattering (GISAXS and GIWAXS) techniques confirmed this effect of bicelles on the SC. These results are probably related to with the permeabilizing effect previously described for the DMPC/DHPC bicelles.

An ex vivo methodology to assess the lipid peroxidation in stratum corneum.

Environmental risks, particularly UV radiation, provide a challenge to the function of the skin barrier. Protective measures such as the use of antioxidant products represent a possible method of providing protection to the skin. This paper reports the development of a non-invasive ex vivo method using tape strips of the outermost layers of stratum corneum (SC) from human volunteers in order to determine the effectiveness of an antioxidant emulsion topically applied to prevent lipid peroxidation (LPO) in the horny layer after an UV irradiation exposure. Two different formulations were used: formulation (A), containing Vitamin A, E and C, and formulation (B) containing fish extract. Both formulations were topically applied in vivo on volunteer forearms; then, a tape stripping of the SC of each volunteer was carried out. The lipid peroxidation was measured ex vivo after an UV irradiation of the SC samples. The amount of SC stripped to evaluate differences in lipid peroxidation, the UV irradiation intensity to form lipid peroxides and the accuracy of lipid peroxide analysis were optimized in this methodology using formulation (A). After an exposure application of seven days, a group of three strips of the outermost layers of SC of volunteers was irradiated with an intensity of 182.7 J/cm(2) to quantify the LPO inhibition. The percentage of LPO inhibition obtained after topical application of both formulations was in the range of 40-58% demonstrating the effectiveness of the formulations topically applied against lipid peroxidation on human SC. This methodology may be used as a quality control tool to determine ex vivo the percentage of the LPO inhibition on human SC for a variety of antioxidants topically applied.