Development of a selective androgen receptor modulator for transdermal use in hypogonadal patients.

We have identified a non-steroidal selective androgen receptor modulator (SARM), termed LY305, that is bioavailable through a transdermal route of administration while highly cleared via hepatic metabolism to limit parent compound exposure in the liver. Selection of this compound and its transdermal formulation was based on the optimization of skin absorption properties using both in vitro and in vivo skin models that supported PBPK modeling for human PK predictions. This molecule is an agonist in perineal muscle while being a weak partial agonist in the androgenic tissues such as prostate. When LY305 was tested in animal models of skeletal atrophy it restored the skeletal muscle mass through accelerated repair. In a bone fracture model, LY305 remained osteoprotective in the regenerating tissue and void of deleterious effects. Finally, in a small cohort of healthy volunteers, we assessed the safety and tolerability of LY305 when administered transdermally. LY305 showed a dose-dependent increase in serum exposure and was well tolerated with minimal adverse effects. Notably, there were no statistically significant changes to hematocrit or HDL after 4-week treatment period. Collectively, LY305 represents a first of its kind de novo development of a non-steroidal transdermal SARM with unique properties which could find clinical utility in hypogonadal men.

Preparation of antioxidant active films based on chitosan: diffusivity study of α-tocopherol into food simulants.

New active films based on chitosan and polycaprolactone blends and containing α-tocopherol were designed for food packaging applications. Mechanical properties, stability against temperature and swelling degree in 50 % ethanol (v/v) were evaluated. Migration kinetics of α-tocopherol from the developed films into butter and food simulants [50 % ethanol (v/v), 95 % ethanol (v/v), and isooctane] at different temperatures were studied. α-Tocopherol was quantified in the food simulants by means of high performance liquid chromatography with diode-array detection at 292 nm. The proposed method exhibited a good sensitivity with a limit of detection of 0.1 mg/L. The kinetics release of α-tocopherol was characterized by determining the partition and the diffusion coefficients by using a mathematical modeling based on Fick's Second Law. The diffusion coefficients obtained ranged between 1.03 × 10(-13) and 2.24 × 10(-12) cm(2)/s for 95 % ethanol (v/v) at 4 and 20 °C, respectively. Developed films maintained the antioxidant activity for more than 20 days.

Instability of an aromatic amine in fatty food and fatty food simulant: characterisation of reaction products and prediction of their toxicity.

It is a well-known fact that amines are not stable in food of a fatty nature. In this study the synthesis and characterisation of the products obtained as a result of the reaction of amines in a fatty medium are reported. Based on the well-known reactions among amines and acid and esters groups, two novel compounds were synthesised using m-xylylenediamine (mXDA), a primary diamine widely used as monomer in the manufacture of food contact materials and two fatty acids, oleic acid and palmitic acid, which occur in most fats. The resulting compounds were two molecules belonging to the family of fatty acid amides, dioleamide and dipalmitamide. A complete characterisation of both products was carried out employing several techniques such as infrared spectroscopy, (1)H- and (13)C-NMR spectroscopy, electron ionisation mass spectrometry, LC-MS/MS and UV spectrometry. The results obtained by the different techniques were well correlated. In the second part of the work, the formation of these compounds in real samples was evaluated. For this purpose a certain volume of olive oil was spiked with a known amount of mXDA. Olive oil was selected as a fatty medium since it is a widely consumed food and additionally is used as a fatty food simulant in migration studies of food contact materials. A method was developed to extract the fatty acid amides from the fatty matrix, which were then identified by LC-MS/MS. The toxicity of the synthesised compounds was predicted using a toxicity estimation software tool.

Analytical method for the simultaneous determination of polyfunctional amines used as monomers in the manufacture of food packaging materials.

This paper describes the development of a multi-analyte method for the determination of polyfunctional amines commonly used as monomers in the manufacture of food contact materials. Amines were analyzed by high-performance-liquid chromatography with diode-array detection (HPLC-DAD) after derivatization with dansyl chloride. The chromatographic analysis and the derivatization conditions were optimized. The proposed method was validated in terms of linearity, limits of detection and repeatabilities. The method showed an excellent sensitivity (LOD≤0.05 µg/mL) and appropriate repeatabilites (RSD (n=7)≤5%)). LC-MS/MS was used as a confirmatory technique. The stability of the amines in five food simulants (distilled water, 3% acetic acid, 10% ethanol, 50% ethanol and olive oil) under the most common testing conditions (10 days at 40 °C) was also studied. Results showed that amines had an acceptable stability in aqueous simulants but in the olive oil a loss of 100% was observed for all analytes.

Rapid multi-analyte quantification of benzophenone, 4-methylbenzophenone and related derivatives from paperboard food packaging.

Photo-initiators are used in printing inks hardened with UV light and one of the most commonly used photo-initiators is benzophenone (BP). Recent notifications under the Rapid Alert System for Food and Feed have shown migration of 4-methylbenzophenone (4-MBP) from packaging into cereals. A specific migration limit exists for BP of 0.6 mg kg(-1) for its use as an additive in plastics. There is no specific European legislation covering cardboard boxes and/or printing inks for food contact use. However, due to the high levels detected, the European Food Safety Authority (EFSA) published recommendations and the Standing Committee for the Food Chain and Animal Health endorsed a limit of 0.6 mg kg(-1) for the sum of BP and 4-MBP. While studies have been published on photo-initiators in the past, there is a fundamental lack of data on 4-MBP especially for its combined analysis with others. We present an HPLC method with diode array detector to simultaneously determine the levels of BP, 4-MBP as well as 7 other possible derivatives from secondary packaging for food applications. The method was tested and applied to 46 samples of paperboard for secondary packaging collected both from supermarkets and directly from a paperboard supplier. In addition, a survey was conducted on recycled paperboard (n = 19) collected from a supplier, to evaluate the background quantity of BP and other derivatives in recycled board. The most abundant photo-initiator found in the survey was BP, in 61% of samples, and 4-MBP was found in 30% of the samples. It seems that these compounds are used to replace one another. Other derivatives were found in minor quantities. Traces of BP were also found in 42% of the samples of recycled, unprinted board.

Migration and diffusion of diphenylbutadiene from packages into foods.

Monitoring of exposure to chemicals from food contact materials is a subject of increasing importance. The concentration of the chemicals and their migration levels, as well as food consumption and packaging usage data, are required to enable calculation of the degree of such exposure. The present study investigated the migration kinetics of diphenylbutadiene (DPBD) from packages into flour, rice, honey, milk powder and toast. Migration was not always negligible, except in honey and skimmed milk powder. Experiments carried out with starch alone enabled us to conclude that diffusion of migrants occurred through starch and fat. Key diffusion parameters were determined (diffusion coefficient and partition coefficient) based on Fick's second equation. The following diffusion coefficients were obtained at 25 degrees C: 2.7 x 10(-10), 3.4 x 10(-11), 3.2 x 10(-10), 8.4 x 10(-11), 8.1 x 10(-11) cm(2) s(-1), for wheat flour, rice, milk powder and toast, with 4 and 21% fat, respectively. A very good fit between experimental and predicted data was achieved. The data obtained in the present study confirm the validity of the mathematical model for predicting migration from Food Contact Materials (FCM) into foods.

Trabajo ganador a la mejor comunicación presentada al XXX Congreso celebrado en JerezIncontinencia urinaria, soja y bolaschinas / No disponible

Hemos estudiado la evolución de mujeres menopáusicas con incontinencia urinaria de esfuerzo a las que propusimos medidas terapéuticasinnovadoras, entre las que se encontraban la toma de fitoestrógenos con la intención de que «engañaran» a la evoluciónnatural del cuerpo de la mujer al llegar a estas edades.También utilizamos medidas clásicas como los ejercicios de rehabilitación del suelo pélvico asociados al mantenimiento de bolas chinasen vagina, magníficas para este fin, aunque más conocidas como juguete sexual.Los resultados obtenidos a los 6 meses de la implantación de estas medidas han sido espectaculares, teniendo en cuenta el bajo costey la inocuidad del tratamiento (AU)

We have studied the evolution of menopausal women with effort Urinary Incontinence to whom we suggested innovative therapeuticmeasures, such as taking with the intention that they «trick» the natural evolution of woman’s body when arriving at these ages.We also use classic measures such as the rehabilitation exercises of the pelvic floor associated with the maintenance of ben wa ballsin vagina, excellent for this purpose, although they are best known as a sexual toy.The obtained results in 6 months from the introduction of these measures have been spectacular taking into account the low cost andthe harmlessness of the treatment (AU)

Development of a multimethod for the determination of photoinitiators in beverage packaging.

Photoinitiators are ink components used in the printing of food packaging. The aim of the present study was to develop a multimethod for the analysis of photoinitiators in paperboard packages and commercial beverage packages. The proposed method is simple and fairly rapid. Extraction is carried out with acetonitrile. A reverse-phase high performance liquid chromatography (HPLC) method with UV detection was developed to quantify the 6 selected photoionitiators. Total HPLC time analysis was 30 min and the flow-rate was 1 mL/min. Method validation parameters such as linearity and detection limit are reported. Recovery of all photoinitiators (at 1 mg/kg) from orange juice was satisfactory (mean = 88.4%; ranging from 84.6% to 93.4%). Recovery of benzophenone and Irgacure 651 was good (ranging from 85.2% to 98.1% and 86.1% to 92.2%, respectively) at the 4 concentrations studied (0.1, 0.2, 0.5, and 1 mg/kg). Commercial beverage packages were analyzed and when photoinitiators were detected, the beverages were also analyzed.

Development of an analytical method for the determination of photoinitiators used for food packaging materials with potential to migrate into milk.

Photoinitiators are used in the curing process during UV printing of food carton labels. The alarm concerning the detection of a photoinitiator, 2-isopropyl thioxanthone (ITX), in food samples packed with cartons printed with UV-cured inks has focused the attention of legislative authorities on the potential migrants from packaging inks into foods. For this reason it is very important to carry out analytical methods for the detection of those compounds in food as potential migrants from packaging. The aim of the present work was to develop a multimethod for the analysis of 6 photoinitiators in milk. The selected photoinitiators were Irgacure 184, benzophenone, Irgacure 651, Irgacure 907, Quantacure ITX, and Quantacure EHA (2-ethylhexyl-4-dimethylaminobenzoate). Milk (10 mL) extraction was carried out by using ammoniac and hexane. The supernatant was evaporated and the residue was redissolved with acetonitrile. Then, the extract was analyzed by HPLC-UV. Calibration lines were carried out over the concentration range of 0.1 to 10 mg/L. The calibration data presented high correlation coefficients (>0.9999). Mean recoveries (n = 6) of the 6 photoinitiators were 83.4% (residual standard deviation = 2.3%) at 0.5 mg/kg and 81.0% (residual standard deviation = 4.6%) at 1 mg/kg. Several milk samples and their respective packaging cartons were analyzed. Results were confirmed by HPLC-mass spectrometry.

«El descuido de ti mismo es tu peor enemigo» Incontinencia urinaria y sus efectosen la salud. Plan de cuidados para la promoción de la salud / No disponible

Llámese CONTINENCIA URINARIA a la capacidad de controlar el momento oportuno de la micción. Facultad de retener la orina. Entre los miembros del Equipo de Enfermería de la Unidad Urológica del Hospital Universitario de Valme queremos promover la seguridad de contar con soluciones que facilitan el control de la incontinencia, con técnicas sencillas de aprender y realizar. La incontinencia urinaria repercute negativamente en el ámbito laboral, social y psicológico. El paciente debe saber que su incontinencia no tiene por qué afectar a ninguno de los aspectos de su vida. Siguiendo las recomendaciones de su enfermera será capaz de afrontar con éxito su nueva situación. Existe un mundo de soluciones para la autonomía vesical que redundarán en su comodidad y bienestar (AU)

We understand by URINARY CONTINENCE the capacity to control the appropriate moment of the urination. Faculty of retaining the urine. Among the members of the Nursing Team of the Urological Unit of the University Hospital of Valme, we want to promote the guarantee of having solutions that facilitate the control of the incontinence, with simple techniques of learning and carrying out. The urinary incontinence has negative effects on the work, social and psychological areas. The patient must know that their incontinence does not necessary have to affect to any aspect of their life. Following the pieces of advice of their nurse they will be able to confront their new situation successfully. There is a world of solutions for the vesical autonomy that will result in their comfort and welfare (AU)

Kinetic migration studies from packaging films into meat products.

One of the main concerns regarding safety of food packaging is the possible migration of chemical substances (monomers and other starting substances, additives, residues) from food contact materials into foods. To evaluate the effect of the fat content and of the temperature of storage on the migration from plastics packaging films into meat products as an important class of foodstuffs, the kinetic mass transport of a model migrant (diphenylbutadiene) from low density polyethylene (LDPE) film in contact with different meat products was investigated. From the data, the diffusion coefficients were calculated for the applied test conditions, by use of a mathematical model. The results showed that migration increased with fat content and storage temperature. Analysis of migration data corresponding to minced pork meat containing different amounts of fat, stored for 10 days at 25°C, revealed an excellent relationship between migration level and fat content. This behaviour was also found for other types of meat products (chicken and pork neck). A simplifying mathematical model was applied to derive effective diffusion coefficients in the polymer which, however, do take kinetic effects in the meat also into account. In the case of pork meat contact, the effective diffusion coefficients derived from mathematical modelling were ten times higher for storage at 25°C (1.88×10(-9)cm(2)s(-1)) than for storage at 5°C (1.2×10(-10)cm(2)s(-1)).

Profiling flavor compounds of potato crisps during storage using solid-phase microextraction.

Headspace solid-phase microextraction (HS-SPME) was studied as a solvent free alternative method for the extraction and characterisation of volatile compounds in stored potato crisps by capillary gas chromatography coupled with mass detection. Better results were obtained when extraction was carried out at 70 degrees C using a divinylbenzene (DVB)-carboxen (CAR)-polydimethylsiloxane fiber. The fiber was exposed for 20 min (extraction time) to the sample headspace, immediately after an equilibrium time of 5 min (time needed to reach the equilibrium between sample and above headspace). A total of 31 compounds were identified in oxidised potato crisps and resulted mainly from the degradation/rearrangement of lipids and carbohydrates.

Determination of hexanal as indicator of the lipidic oxidation state in potato crisps using gas chromatography and high-performance liquid chromatography.

Hexanal (an oxidative state indicator) formed in the headspace of potato crisps during storage was evaluated using two different procedures. First, solid-phase microextraction, an innovative sampling preparation methodology was used. It consisted on the absorption of analytes directly from samples and subsequent thermal desorption on the gas chromatograph (GC) injector. Then, a reversed-phase high-performance liquid chromatographic technique (HPLC) was employed to quantify hexanal in the form of 2,4-dinitrophenylhydrazone derivative. Methods were evaluated in what concerns to validation parameters such as linearity, repeatibility and detection limit. GC (LOD = 1 ng/ml) method resulted in more sensitive method than HPLC (LOD = 9 ng/ml). The most suitable technique for hexanal measurement was selected.

An HPLC method for the quantification of sterols in edible seaweeds.

This study presents an HPLC method for the quantification of sterols in edible seaweeds. Sterols were identified by HPLC/mass spectrometry (HPLC-MS) in positive APCI mode. The samples were saponified by refluxing with 1 m ethanolic KOH, and the non-saponifiable fraction was extracted with hexane. Sterols were quantified by HPLC with UV detection (HPLC-UV), on a 15 x 0.4 cm Kromasil 100 C(18) 5 micro m column (mobile phase 30:70 v/v methanol:acetonitrile; fl ow rate 1.2 mL/min; column temperature 30 degrees C; detection wavelength 205 nm). Method repeatability for fucosterol was good (coefficient of variation 2.4%). Sterol contents were determined in canned or dried brown seaweeds (Himanthalia elongata, Undaria pinnatifida, Laminaria ochroleuca) and red seaweeds (Palmaria sp., Porphyra sp.). The predominant sterol was fucosterol in brown seaweeds (83-97% of total sterol content; 662-2320 micro g/g dry weight), and desmosterol in red seaweeds (87-93% of total sterol content; 187-337 micro g/g dry weight).

Comparison between high-performance liquid chromatography and gas chromatography methods for fatty acid identification and quantification in potato crisps.

A reversed-phase high performance liquid chromatographic (RP-HLPC) method was compared with a gas chromatography-flame ionization detection (GC-FID) method for determining fatty acids in potato crisps. Different extraction procedures were used. Fatty acids were quantified by linear regression. Both methods presented good precision (R.S.D. < or = 5.88%) and recovery (> or = 82.31%). The precision using HPLC method was slightly better than for GC-FID method. There was good agreement between the fatty acid composition of potato crisps analysed by both methods. For most purposes the HPLC method would be better. However, when more fatty acids need to be analysed, GC is a more suitable method.

Simultaneous determination of thiamine and riboflavin in edible marine seaweeds by high-performance liquid chromatography.

This study presents a high-performance liquid chromatography (HPLC) method for simultaneous determination of thiamine and riboflavin and the results of its application to a number of edible seaweeds that are sampled in dried form (Himanthalia elongata, Laminaria ochroleuca, Undaria pinnatifida, Palmaria sp., and Porphyra sp.) or as canned food (H. elongata and Saccorhiza polyschides). Samples are prepared by acid and enzymatic hydrolysis. Optimized conditions for reversed-phase HPLC with fluorescence detection are as follow: column, Kromasil 100 C18; column temperature, 35 degrees C; mobile phase, a 72:28 (v/v) mixture of 0.005 M ammonium acetate (pH 6.7)-methanol; and flow rate, 1.35 mL/min. With these conditions, recovery is 95.52% for thiamine and 90.08% for riboflavin, and the method precision (relative standard deviation) is 2.66% for thiamine and 2.21% for riboflavin. On a dry weight basis, thiamine contents range from 0.14 microg/g in dried H. elongata to 2.02 microg/g in dried Porphyra and riboflavin contents from 0.31 microg/g in canned H. elongata to 6.15 microg/g in dried Porphyra.

Determination of the uronic acid composition of seaweed dietary fibre by HPLC.

A high-performance liquid chromatographic (HPLC) method is described for determination of the ratio of beta-d-mannuronic acid to alpha-l-guluronic acid (M/G ratio) in dietary fibre of edible seaweeds. Total dietary fibre (TDF) content was determined gravimetrically. The TDF fraction was hydrolysed with 12 m and 1 m H(2)SO(4), then neutralized with AG 4 x 4 resin. The uronic acids were separated in a Tracer Extrasil SAX 5 micro m column (25 cm x 4 mm) at 35 degrees C, with 2 mm KH(2)PO(4) containing 5% methanol as mobile phase at a fl ow rate of 1.5 mL/min. The detection wavelength was UV 210 nm. The chromatographic identifications of beta-d-mannuronic acid and alpha-l-guluronic acid were confirmed by liquid chromatography-mass spectrometry (LC-MS). The method precision was 1.4% for beta-d-mannuronic acid and 3.5% for alpha-l-guluronic acid. The method was used to determine M/G ratio in canned seaweeds (Saccorhiza polyschides and Himanthalia elongata) and in dried seaweeds (H. elongata, Laminaria ochroleuca, Undaria pinnatifida, Palmaria sp. and Porphyra sp.).

Determination of bisphenol A in, and its migration from, PVC stretch film used for food packaging.

Bisphenol A (BPA) is used as an additive in polyvinyl chloride (PVC) products, including stretch films used for food packaging. The BPA contents were investigated of several brands of stretch film bought locally but marketed internationally or throughout Spain and which were presumably produced at different manufacturing plants. Their major components were identified by FTIR (Fourier Transform Infrared Spectrometry) and horizontal attenuated total reflectance, and the migration of BPA from these materials into the standard European Union food simulants was determined by high-performance liquid chromatography (HPLC) using both fluorescence (FL) and ultraviolet (UV) detection, the identity of the analyte being confirmed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). The two HPLC detection methods had different detection limits (30 microg x l(-1) for UV, 3 microg x l(-1) for FL), but afforded virtually identical BPA determinations for the samples tested. BPA contents ranging from 40 to 100 mg x kg(-1) were found in three of the five PVC-based films analysed, and a content of 500 mg x kg(-1) was found in a fourth; for these determinations, extraction into acetonitrile was used. In standard tests of migration into water, 3% acetic acid and olive oil over 10 days at 40 degrees C, migration from a given film was in all cases greatest into olive oil. Migration from the films with non-zero BPA contents ranged from 3 to 31 microg x dm(-2), values higher than those reported for many other food-contact materials, but lower than the European Union specific migration limit for BPA. PVC stretch film nevertheless may make a significant contribution to contamination of foodstuffs by BPA, and should be taken into account in estimating BPA intake or exposure to this substance.

Evaluating the migration of ingredients from active packaging and development of dedicated methods: a study of two iron-based oxygen absorbers.

The behaviour of two commercial oxygen-scavenging products with respect to migration of active ingredients into foodstuffs was investigated. Migrants were identified, and by using appropriate analytical methods, migration was determined in a variety of liquid, solid or gelled food simulants and foods. Simulants were chosen to cover a range of water activities and viscosities. Foods and the gelled food simulant agar were packed with and without vacuum, and with the oxygen scavenger in various locations relative to the packed food. The main migrants, as identified by X-ray fluorescence spectrometry, infrared spectroscopy and scanning electron microscopy with energy-dispersive spectrometry were Na(+) and Cl(-) in non-acidic aqueous simulants, and Na(+), Cl(-) and Fe(2+) in 3% acetic acid. Migration into aqueous simulants exceeded the current European Union limit for total migration from plastic materials (assumed to be currently applicable to these systems) and was probably excessive by any reasonable standard. However, neither oxygen scavenger appeared to release significant quantities of migrants into solid foods when the scavenger was properly located in the package and the packing process does not favour the contents becoming wet by water released from the food.

[Silent ischemic heart disease in patient with Wegener's necrotizing glomerulonephritis]. / Cardiopatía isquémica silente en paciente con glomerulonefritis necrotizante por enfermedad de Wegener.

Wegener's granulomatosis is a necrotizing vasculitis disorder that usually presents with clinical involvement of the upper and lower respiratory tract in association with renal disease. Although Wegener's granulomatosis can affect other systems, such as the eye, skin, joints, muscle, nerves, gastrointestinal tract and heart, cardiac involvement is traditionally believed to be rare, even though coronary vasculitis can be demonstrated at postmortem examination. We report a patient who has both respiratory and renal involvement who died unexpectedly following a silent myocardial infarct after a period of clinical improve induced by treatment with cyclophosphamide and prednisone.