Effect of cationic surfactant on the physicochemical and antibacterial properties of colloidal systems (emulsions and microemulsions).

Colloidal systems have been used to encapsulate, protect and release essential oils in mouthwashes. In this study, we investigated the effect of cetylpyridinium chloride (CPC) on the physicochemical properties and antimicrobial activity of oil-in-water colloidal systems containing tea tree oil (TTO) and the nonionic surfactant polysorbate 80. Our main aim was to evaluate whether CPC could improve the antimicrobial activity of TTO, since this activity is impaired when this essential oil is encapsulated with polysorbate 80. These systems were prepared with different amounts of TTO (0-0.5% w/w) and CPC (0-0.5% w/w), at a final concentration of 2% (w/w) polysorbate 80. Dynamic light scattering (DLS) results revealed the formation of oil-swollen micelles and oil droplets as a function of TTO concentration. Increases in CPC concentrations led to a reduction of around 88% in the mean diameter of oil-swollen micelles. Although this variation was of only 20% for the oil droplets, the samples appearance changed from turbid to transparent. The surface charge of colloidal structures was also markedly affected by the CPC as demonstrated by the transition in zeta potential from slightly negative to highly positive values. Electron paramagnetic resonance (EPR) studies showed that this transition is followed by significant increases in the fluidity of surfactant monolayer of both colloidal structures. The antimicrobial activity of colloidal systems was tested against a Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureaus) bacteria. Our results revealed that the inhibition of bacterial growth is observed for the same CPC concentration (0.05% w/w for E. coli and 0.3% w/w for S. aureus) regardless of TTO content. These findings suggest that TTO may not act as an active ingredient in polysorbate 80 containing mouthwashes.

Chromatographic fingerprint-based analysis of extracts of green tea, lemon balm and linden: II. Simulation of chromatograms using global models.

Medicinal plants contain a large variety of chemical compounds in highly variable concentrations, so the quality control of these materials is especially complex. With this purpose, regulatory institutions have accepted chromatographic fingerprints as a valid tool to perform the analyses. In order to improve the results, separation conditions that maximise the number of detected peaks in these chromatograms are needed. This work reports the extension of a simulation strategy, based on global retention models previously developed for selected compounds, to all detected peaks in the full chromatogram. Global models contain characteristic parameters for each component in the sample, while other parameters are common to all components and describe the combined effects of column and solvent. The approach begins by detecting and measuring automatically the position of all peaks in a chromatogram, obtained preferably with the slowest gradient. Then, the retention time for each detected component is fitted to find the corresponding solute parameter in the global model, which leads to the best agreement with the measured experimental value. The process is completed by developing bandwidth models for the selected compounds used to build the global retention model based on gradient data, which are applied to all peaks in the chromatogram. The usefulness of the simulation approach is demonstrated by predicting chromatographic fingerprints for three medicinal plants with specific separation problems (green tea, lemon balm and linden), using several multi-linear gradients that lead to problematic predictions.

Chromatographic fingerprint-based analysis of extracts of green tea, lemon balm and linden: I. Development of global retention models without the use of standards.

We report here the improvement of a procedure to obtain global models, able to describe the retention behaviour of several sample components simultaneously. The reported global models include parameters that account for the general effects of column and solvent on retention and are common for all components, whereas other parameters are specific of each sample component. These models are fitted by alternate regression and offer a prediction performance comparable to individual retention models. The approach is suitable to samples of natural products including a large number of components in extremely diverse concentrations and in the absence of standards. Guidelines are given for the successful development of sample-oriented experimental designs (i.e. adapted to the elution of the components of the natural products), constituted by multi-linear gradients. These designs also facilitate peak tracking. The model proposed by Neue and Kuss to describe the retention was found to yield the best predictions. The approach is applied to the extracts of samples of green tea, lemon balm and linden, yielding excellent predictions of retention for selected components.

In Vitro Tumor Cell Growth Inhibition Induced by Lophocereus marginatus (DC.) S. Arias and Terrazas Endophytic Fungi Extracts.

Endophytic fungi have become potential sources of antitumor agents, particularly against antineoplastic-resistant cancer cells, with marginal or nil adverse effects for the oncological patient. Endophytic fungi were isolated from stems of the Lophocereus marginatus cactus, commonly found in Mexico. Methanol extracts were then obtained from fungus liquid cultures and their effects on tumor cell growth against murine lymphoma (L5178Y-R), human colorectal adenocarcinoma (HT-29), and human breast cancer (MCF-7) cells were evaluated at concentrations ranging from 31 µg/mL to 250 µg/mL via the colorimetric 3- [4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide reduction assay, using monkey kidney epithelial (MA-104) and human peripheral mononuclear (PBMC) cells as controls. Furthermore, we obtained the IC50 and the selectivity index (SI) was calculated from the IC50 ratio of normal and tumor cells. In addition, molecular identification of fungi showing cytotoxic activity was determined, using internal transcribed spacer molecular markers. PME-H001, PME-H002, PME-H005, PME-H007, and PME-H008 filamentous fungus strain extracts showed significant (p < 0.05) tumor cell growth inhibition. In particular, they significantly (p < 0.05) inhibited L5178Y-R cell growth, whereas the least susceptible cell line was HT-29. The endophytic strain PME-H008 of Cladosporium sp. caused the highest growth inhibition percentage against L5178Y-R and HT-29 cells with 96.6% (p < 0.01) and 42.5% (p < 0.05) respectively, and the highest SIs against L5178Y-R cells with 2.4 and 2.9 for MA-104 and PBMCs, respectively, whereas the PME-H005 extract showed SIs of 2.77 and 1.5 against MCF-7 and L5178Y-R cells, respectively, as compared with PBMCs. In addition, the endophytic strain PME-H007 of Metarhizium anisopliae caused the highest percentage of growth inhibition (p < 0.01) against MCF-7 cells with 55.8% at 250 µg/mL. We demonstrated in vitro antitumor effects of L. marginatus endophytic fungi. Further research will involve the isolation and in vivo testing of bioactive compounds.

Global retention models and their application to the prediction of chromatographic fingerprints.

The resolution of samples containing unknown compounds of different nature, or without standards available, as is the case of chromatographic fingerprints, is still a challenge. Possibly, the most problematic aspect that prevents systematic method development is finding models that describe without bias the retention behaviour of the compounds in the samples. In this work, the use of global models (able to describe the whole sample) is proposed as an alternative to the use of individual models for each solute. Global models contain parameters that are specific for each solute, while other parameters ‒related to the column and solvent‒ are common for all solutes. A special regression procedure is presented for the construction of global models, which are applied to predict highly complex chromatograms, such as chromatographic fingerprints, for diverse experimental conditions in isocratic and gradient elution. Another interesting application is the prediction of molecular properties, such as log Po/w, from the specific solute parameters of the global models. The examined adapted models are based on the equations proposed by Snyder, Schoenmakers, Neue and Kuss, Jandera, and Bosch Rosés to describe the retention. In all cases, the predictive capability was very satisfactory. Two cases of study were considered: chromatograms of camomile extracts analysed using acetonitrile gradients, and a set of 145 known compounds in a wide range of structures and functionalities, eluted isocratically with acetonitrile/water mobile phases.

Bioactive Products From Plant-Endophytic Gram-Positive Bacteria.

Endophytes constitute plant-colonizing microorganisms in a mutualistic symbiosis relationship. They are found in most ecosystems reducing plant crops' biotic and abiotic stressors by stimulating immune responses, excluding plant pathogens by niche competition, and participating in antioxidant activities and phenylpropanoid metabolism, whose activation produces plant defense, structural support, and survival molecules. In fact, metabolomic studies have demonstrated that endophyte genes associated to specific metabolites are involved in plant growth promotion (PGP) by stimulating plant hormones production such as auxins and gibberellins or as plant protective agents against microbial pathogens, cancer, and insect pests, but eco-friendly and eco-safe. A number of metabolites of Gram-positive endophytes isolated from agriculture, forest, mangrove, and medicinal plants, mainly related to the Firmicutes phyla, possess distinctive biocontrol and plant growth-promoting activities. In general, Actinobacteria and Bacillus endophytes produce aromatic compounds, lipopeptides, plant hormones, polysaccharides, and several enzymes linked to phenylpropanoid metabolism, thus representing high potential for PGP and crop management strategies. Furthermore, Actinobacteria have been shown to produce metabolites with antimicrobial and antitumor activities, useful in agriculture, medicine, and veterinary areas. The great endophytes diversity, their metabolites production, and their adaptation to stress conditions make them a suitable and unlimited source of novel metabolites, whose application could reduce agrochemicals usage in food and drugs production.

Is the ISAC 112 Microarray Useful in the Diagnosis of Pollinosis in Spain?

BACKGROUND: Multiple sensitization is frequent among pollen-allergic patients. The goal of this study was to determine the diagnostic accuracy of the ImmunoCAP ISAC 112 (ISAC112) microarray in allergy to pollen from several taxa and its clinical utility in a Spanish population. METHODS: Specific IgE was determined in 390 pollen-allergic patients using the ISAC112 microarray. Diagnostic accuracy (sensitivity, specificity, predictive values, and area under the ROC curve) was calculated for the diagnosis of allergy to pollen from grass (n=49), cypress (n=75), olive tree (n=33), plane tree (n=63), and pellitory of the wall (n=17) and compared with that of the singleplex ImmunoCAP immunoassay. RESULTS: The sensitivity of the ISAC112 microarray ranged from 68.2% for allergy to plane tree pollen to 93.9% for allergy to grass pollen. The specificity was >90%. The AUC for the diagnosis of allergy to plane tree pollen was 0.798, whereas the AUC for the remaining cases was ≥0.876. The accuracy of ISAC112 was higher than that of ImmunoCAP for plane tree pollen and similar for the remaining pollens. The frequency of sensitization to most species-specific allergenic components and profilins varied between the different geographical regions studied. A total of 73% of pollen-allergic patients were sensitized to species-specific components of more than 1 pollen type. CONCLUSIONS: The ISAC112 microarray is an accurate tool for the diagnosis of allergy to pollen from grass, cypress, olive tree, plane tree, and pellitory of the wall. The features of the ISAC112 microarray are similar or superior (in the case of plane tree pollen) to those of ImmunoCAP. This microarray is particularly useful for the etiologic diagnosis of pollinosis in patients sensitized to multiple pollen species whose pollination periods overlap.

Dermoscopic Findings of Jellyfish Stings Caused by Pelagia noctiluca.

BACKGROUND AND OBJECTIVES: Jellyfish are free-living members of the phylum Cnidaria who share a specialized stinging cell, the cnidocyte. Pelagia noctiluca is the most frequent and toxic jellyfish species found in the Balearic beaches and cnidocytes are arranged in pigmented clusters called "warts". Dermoscopy continues to expand its use much beyond the pigmentary lesions and to date, there is no data regarding dermoscopic findings in jellyfish stings. The aim of the present work was to study the dermoscopic findings of jellyfish stings in the island of Mallorca. PATIENTS AND METHODS: We retrospectively reviewed the clinical and dermoscopic images of 25 episodes of jellyfish stings caused by P. noctiluca that occurred between 2009 and 2015. RESULTS: Overall, the following dermoscopic features were found: brown dots (84%), pinkish hue (56%), pinpoint brown crusts (44%), scale-crust (40%), brown "Chinese characters pattern" (32%), "serpentine" ulceration (28%), linear purpura (20%), and whitish-yellow crusts (15%). Vessels were mainly dotted (36%) or reticular (16%). Scale-crust, serpentine ulceration and pinkish hue were significantly more frequent in lesions older than 2 days. CONCLUSIONS AND LIMITATIONS: Our study identifies 4 dermoscopic features that may represent the contact with P. noctiluca cnidocytes: brown dots, brown "Chinese characters pattern", pinpoint brown crusts and whitish-yellow crusts. A peculiar finding of "serpentine ulceration" with brown dots would be very suggestive of P. noctiluca sting. We believe dermoscopy is a valuable tool in the diagnosis of jellyfish stings when a clear history of contact is lacking. Further studies are needed to validate our findings in other jellyfish species.

Is the ISAC 112 microarray useful in the diagnosis of pollinosis in Spain?

Background: Multiple sensitization is frequent among pollen-allergic patients. The goal of this study was to determine the diagnostic accuracy of the ImmunoCAP ISAC 112 (ISAC112) microarray in allergy to pollen from several taxa and its clinical utility in a Spanish population. Methods: Specific IgE was determined in 390 pollen-allergic patients using the ISAC112 microarray. Diagnostic accuracy (sensitivity, specificity, predictive values, and area under the ROC curve) was calculated for the diagnosis of allergy to pollen from grass (n=49), cypress (n=75), olive tree (n=33), plane tree (n=63), and pellitory of the wall (n=17) and compared with that of the singleplex ImmunoCAP immunoassay. Results: The sensitivity of the ISAC112 microarray ranged from 68.2% for allergy to plane tree pollen to 93.9% for allergy to grass pollen. The specificity was >90%. The AUC for the diagnosis of allergy to plane tree pollen was 0.798, whereas the AUC for the remaining cases was ≥0.876. The accuracy of ISAC112 was higher than that of ImmunoCAP for plane tree pollen and similar for the remaining pollens. The frequency of sensitization to most species-specific allergenic components and profilins varied between the different geographical regions studied. A total of 73% of pollen-allergic patients were sensitized to species-specific components of more than 1 pollen type. Conclusions: The ISAC112 microarray is an accurate tool for the diagnosis of allergy to pollen from grass, cypress, olive tree, plane tree, and pellitory of the wall. The features of the ISAC112 microarray are similar or superior (in the case of plane tree pollen) to those of ImmunoCAP. This microarray is particularly useful for the etiologic diagnosis of pollinosis in patients sensitized to multiple pollen species whose pollination periods overlap (AU)

Introducción: La sensibilización a múltiples pólenes es frecuente entre los pacientes alérgicos a polen. El objetivo de este estudio fue determinar la exactitud diagnóstica de la micromatriz ImmunoCAP ISAC 112 (ISAC112) en alergia a polen de diversos taxones y su utilidad clínica en una población española. Métodos: Se determinó IgE específica mediante ISAC112 en 390 pacientes polínicos. Se calculó su exactitud diagnóstica (sensibilidad, especificidad, valores predictivos y área bajo la curva ROC) para el diagnóstico de alergia a polen de gramíneas (n=49), ciprés (n=75), olivo (n=33), plátano de sombra (n=63) y parietaria (n=17) y se comparó con la de ImmunoCAP monocomponente (CAP). Resultados: La sensibilidad de ISAC112 osciló entre 68,2% para alergia a polen de plátano de sombra y 93,9% a polen de gramíneas. La especificidad se situó por encima del 90% en todos los casos. El área bajo la curva (AUC) de la curva ROC para diagnóstico de alergia a polen de plátano fue de 0,798. El resto de AUC fueron ≥ 0,876. La exactitud diagnóstica de ISAC112 fue superior a la de CAP para la alergia a polen de plátano de sombra y similar para el resto de pólenes estudiados. La frecuencia de sensibilización a la mayoría de componentes alergénicos genuinos y a profilinas varió entre las diferentes zonas. El 73 % de los pacientes polínicos estaban sensibilizados a componentes genuinos de más de un tipo polínico. Conclusiones: ISAC112 es una herramienta exacta para el diagnóstico de alergia al polen de gramíneas, ciprés, olivo, plátano de sombra y parietaria, con prestaciones similares o superiores, en el caso de alergia a polen de plátano de sombra, a las de CAP. Es especialmente útil para el diagnóstico etiológico de la polinosis en pacientes con sensibilizaciones a múltiples pólenes con periodos de polinización solapados (AU)

Actualización en artritis psoriásica / Psoriatic Arthritis: An Update

En los últimos años se ha ampliado el conocimiento de aspectos clínicos y patogénicos de la artritis psoriásica, que justifican la presente revisión. Se han identificado vías comunes de activación de la respuesta inflamatoria relacionada con la inmunidad innata, como el eje IL12/IL23 y numerosos genes determinantes de la susceptibilidad a ambas enfermedades, y diferencias en el fenotipo. El desarrollo de biomarcadores de diagnóstico precoz, pronósticos y predictivos de la destrucción osteoarticular y la respuesta al tratamiento son también de interés creciente. Recientemente se han descrito también diferencias importantes en la respuesta sobre el proceso de neoformación ósea entre FAME y biológicos. Asimismo, se ha puesto de manifiesto la necesidad de disponer de métodos de cribado fiables, en especial para identificar precozmente las formas oligoarticulares, y establecer criterios de derivación prácticos que permitan ofrecer una atención especializada, principalmente en el contexto de unidades interdisciplinares de nueva creación

Advances in our understanding of the pathogenesis of psoriatic arthritis and clinical aspects of the disease justify the present review. Studies have identified common inflammatory pathways related to the innate immune response, such as the IL-12/IL-23 axis, along with numerous genes that affect susceptibility to both diseases and influence phenotypic development. Interest has grown in biomarkers that can be used for early diagnosis or prognosis or to predict joint destruction and the response to treatment. Recent reports describe important differences between the effects of disease-modifying antirheumatic drugs and biologics on the process of new bone formation. Other issues that have been discussed include the need for reliable screening methods, particularly for early detection of oligoarticular arthritis, and for protocols to guide referral to specialists, especially in newly created multidisciplinary practices. © 2013 Elsevier España, S.L.U. and AEDV. All rights reserved

Antioxidant effect of 4-nerolidylcatechol and α-tocopherol in erythrocyte ghost membranes and phospholipid bilayers.

4-Nerolidylcatechol (4-NC) is found in Pothomorphe umbellata root extracts and is reported to have a topical protective effect against UVB radiation-induced skin damage, toxicity in melanoma cell lines, and antimalarial activity. We report a comparative study of the antioxidant activity of 4-NC and α-tocopherol against lipid peroxidation initiated by two free radical-generating systems: 2,2'-azobis(2-aminopropane) hydrochloride (AAPH) and FeSO4/H2O2, in red blood cell ghost membranes and in egg phosphatidylcholine (PC) vesicles. Lipid peroxidation was monitored by membrane fluidity changes assessed by electron paramagnetic resonance spectroscopy of a spin-labeled lipid and by the formation of thiobarbituric acid-reactive substances. When lipoperoxidation was initiated by the hydroxyl radical in erythrocyte ghost membranes, both 4-NC and α-tocopherol acted in a very efficient manner. However, lower activities were observed when lipoperoxidation was initiated by the peroxyl radical; and, in this case, the protective effect of α-tocopherol was lower than that of 4-NC. In egg PC vesicles, malondialdehyde formation indicated that 4-NC was effective against lipoperoxidation initiated by both AAPH and FeSO4/H2O2, whereas α-tocopherol was less efficient in protecting against lipoperoxidation by AAPH, and behaved as a pro-oxidant for FeSO4/H2O2. The DPPH (2,2-diphenyl-1-picrylhydrazyl) free-radical assay indicated that two free radicals were scavenged per 4-NC molecule, and one free radical was scavenged per α-tocopherol molecule. These data provide new insights into the antioxidant capacity of 4-NC, which may have therapeutic applications for formulations designed to protect the skin from sunlight irradiation.

Antioxidant effect of 4-nerolidylcatechol and -tocopherol in erythrocyte ghost membranes and phospholipid bilayers

4-Nerolidylcatechol (4-NC) is found in Pothomorphe umbellata root extracts and is reported to have a topical protective effect against UVB radiation-induced skin damage, toxicity in melanoma cell lines, and antimalarial activity. We report a comparative study of the antioxidant activity of 4-NC and α-tocopherol against lipid peroxidation initiated by two free radical-generating systems: 2,2′-azobis(2-aminopropane) hydrochloride (AAPH) and FeSO4/H2O2, in red blood cell ghost membranes and in egg phosphatidylcholine (PC) vesicles. Lipid peroxidation was monitored by membrane fluidity changes assessed by electron paramagnetic resonance spectroscopy of a spin-labeled lipid and by the formation of thiobarbituric acid-reactive substances. When lipoperoxidation was initiated by the hydroxyl radical in erythrocyte ghost membranes, both 4-NC and α-tocopherol acted in a very efficient manner. However, lower activities were observed when lipoperoxidation was initiated by the peroxyl radical; and, in this case, the protective effect of α-tocopherol was lower than that of 4-NC. In egg PC vesicles, malondialdehyde formation indicated that 4-NC was effective against lipoperoxidation initiated by both AAPH and FeSO4/H2O2, whereas α-tocopherol was less efficient in protecting against lipoperoxidation by AAPH, and behaved as a pro-oxidant for FeSO4/H2O2. The DPPH (2,2-diphenyl-1-picrylhydrazyl) free-radical assay indicated that two free radicals were scavenged per 4-NC molecule, and one free radical was scavenged per α-tocopherol molecule. These data provide new insights into the antioxidant capacity of 4-NC, which may have therapeutic applications for formulations designed to protect the skin from sunlight irradiation.

Vitamin D, sunlight and longevity.

Humans acquire vitamin D through skin photosynthesis and digestive intake. Two hydroxylations are needed to obtain the bioactive compound, the first produces 25-hydroxyvitamin D [25(OH)D], and the second 1,25-dihydroxyvitamin D [1,25(OH)2D]. There is no consensus regarding the appropriate cut-off level to define the normal serum 25(OH)D range. Experimental, epidemiological and clinical studies have related low vitamin D status with longevity. Although some results are controversial, low serum 25(OH)D levels have been linked to all-cause, cardiovascular, cancer and infectious related mortality. Throughout life span a significant proportion of human beings display insufficient (20-30 ng/mL) or deficient (<20 ng/mL) serum 25(OH)D levels. Appropriate lifestyle changes, such as regular short exposures to sunlight (15 min a day), and an adequate diet that includes vitamin D rich components, are not always easily accomplished. Studies relating to vitamin D supplementation have methodological limitations or are based on relatively low doses. Therefore, dosages used for vitamin D supplementation should be higher than those traditionally suggested. In this sense, there is an urgent need for prospective controlled studies using high daily vitamin D doses (2,000 IU or higher) including cardiovascular, cancer, infectious and other endpoints. Relationship between vitamin D and health outcomes is not linear, and there are probably various optimal vitamin D levels influencing different endpoints.

Grass pollen, aeroallergens, and clinical symptoms in Ciudad Real, Spain.

BACKGROUND: In allergic individuals, onset of symptoms is related to atmospheric pollen grain counts and aeroallergen concentrations. However, this relationship is not always clear. OBJECTIVES: To analyze the correlation between grass pollen grain and aeroallergen concentrations in Ciudad Real, Spain, during the year 2004 and establish their association with symptoms in patients with allergic asthma, rhinitis, or both. METHODS: Two different samplers were used to assess allergen exposure: a Burkard spore trap to collect pollen grains and a high-volume air sampler to collect airborne particles. Individual filters were extracted daily in phosphate-buffered serum and analyzed by enzyme-linked immunosorbent assay based on serum containing high titers of specific immunoglobulin (Ig) E to grasses. The study population comprised 27 grass-allergic patients whose symptoms and medication were recorded daily. RESULTS: Grass pollens were detected between April 28 and July 18. There was a positive correlation between pollen grain counts and symptoms (r = 0.62; P > .001). Grass aeroallergens were detected not only during the grass pollination period, but also before and after this period. There was also a very significant correlation between aeroallergen levels and symptoms (r = 0.76; P < .0001). The threshold level for grass pollen was 35 grains/m3. CONCLUSIONS: Grass-related allergenic activity is present throughout the year, demonstrating the existence of aeroallergens outside the pollen season. Symptoms in allergic patients may be related to airborne particle concentrations. This fact should be taken into account in the clinical follow-up and management of allergic patients.

Role of vegetables and fruits in Mediterranean diets to prevent hypertension.

BACKGROUND/OBJECTIVES: Several studies support the effectiveness of increasing the consumption of fruits and vegetables (F&V) to prevent hypertension. However, none of them have been conducted in a Mediterranean setting. The aim of this study was to assess the association between F&V consumption and the risk of hypertension. SUBJECTS/METHODS: A prospective Mediterranean study (the SUN cohort), including 8594 participants aged 20-95 years (mean, 41.1) with median follow-up of 49 months. RESULTS: Analyses according to the joint classification by olive oil and F&V consumption showed a significant inverse relation between F&V consumption and the risk of hypertension only among participants with a low olive oil consumption (<15 g per day). Also, tests for trend were significant only in the low olive oil intake stratum. CONCLUSIONS: We found a statistically significant interaction (P=0.01) between olive oil intake and F&V consumption. These data suggest a sub-additive effect of both food items.

[Importance of PSA velocity and PSA density in the prediction of prostate cancer in TURP or open prostatectomy specimen of patients with previous negative prostate biopsy]. / Importancia de la velocidad y la densidad de PSA en la predicción de cáncer de próstata en la pieza de RTU o adenomectomía de pacientes con biopsia prostática previa negativa.

PURPOSE: To determine variables related to the finding of prostate cancer (PC) in patients who underwent surgery following at least one negative prostate biopsy (PB). MATERIALS AND METHODS: A retrospective study of 170 patients who underwent transurethral resection of the prostate (TURP) or open prostatectomy between 1999 and 2007, following one or more negative PB sets. A multivariate logistic regression analysis was carried out in order to determine variables related to the finding of PC. The predictive capacity of PSA, PSA-density and PSA-velocity was assessed by means of ROC curves and the area under the curve (AUC). Sensitivity, specificity and predictive values were determined for several PSA-density and PSA-velocity cut-off points. RESULTS: Open prostatectomy was carried out on 104 patients (61.18%) and TURP on 66 (38.82%). PC was detected in the surgical specimen of 16 patients (9.41%). Variables associated with the finding of PC in the surgical specimen were PSA-density (OR: 1.47; 95% CI: 1.22-6.64; p: 0.007) and PSA-velocity (OR: 2.87; 95% CI: 1.60-5.12: p < 0.001). The AUCs were 0.746, 0.793 and 0.832, for PSA, PSA-density and PSA-velocity, respectively. The most sensitive PSA-density and PSA-velocity cut-off points in detecting PC were 0.15 and 1 ng/ml/year, respectively. Patients without PC showed a median PSA reduction of 9.35 ng/ml (-2.40 - 35.40), following surgery. CONCLUSIONS: PSA-density and PSA-velocity in particular, allow for the prediction of the presence of PC in the TURP or open prostatectomy specimen of patients with previously negative PBs. Diagnostic TURP could prove useful in patients with clinical suspicion of PC, susceptible to curative treatment, with PSA-velocity > 1l ng/ml/year and one or more negative saturation biopsies.

Importancia de la velocidad y la densidad de PSA en la predicción de cáncer de próstata en la pieza de RTU o adenomectomía de pacientes con biopsia prostática previa negativa / Importance of PSA velocity and PSA density in the prediction of prostate cancer in TURP or open prostatectomy specimen of patients with previous negative prostate biopsy

Objetivo: Determinar variables relacionadas con el hallazgo de cáncer de próstata (CaP) en pacientes sometidos a cirugía prostática tras al menos una biopsia prostática (BP) negativa. Material y métodos: Estudio retrospectivo de 170 pacientes sometidos a resección transuretral de próstata (RTUP) o adenomectomía entre 1999 y 2007, después de una o más BPs negativas. Se realizó un análisis multivariado de regresión logística para identificar variables relacionadas con la presencia de CaP. La capacidad predictiva de PSA, PSA densidad y PSA velocidad se determinó mediante curvas ROC y su área bajo la curva (ABC). Se analizó la sensibilidad, especificidad y valores predictivos para diversos puntos de corte de PSA densidad y PSA velocidad. Resultados: Se realizó adenomectomía en 104 pacientes (61,18%) y RTUP en 66 (38,82%). Se detectó CaP en la pieza quirúrgica de 16 pacientes (9,41%). Las variables asociadas al hallazgo de CaP en la pieza quirúrgica fueron PSA densidad (OR:1,47;95% IC:1,22-6,64; p:0,007) y PSA velocidad (OR:2,87;95% IC:1,60-5,12; p<0,001). Las ABC ROC fueron 0,746, 0,793 y 0,832, para PSA, PSA densidad y PSA velocidad, respectivamente. Los puntos de corte de PSA densidad y PSA velocidad con mayor sensibilidad y especificidad en la detección de CaP fueron 0,15 y 1 ng/ml/año, respectivamente. Los pacientes sin CaP mostraron una reducción mediana de PSA de 9,35 ng/ml (-2,40 – 35,40), después de la cirugía. Conclusiones: El PSA densidad y el PSA velocidad en particular, permiten predecir la presencia de CaP en la pieza de RTUP o adenomectomía, de pacientes con BPs previas negativas. La RTUP diagnóstica podría ser recomendada en pacientes con sospecha clínica de CaP, susceptibles de tratamiento curativo, con PSA velocidad >1ng/ml/año y una o más biopsias de saturación previas negativas (AU)

Purpose: To determine variables related to the finding of prostate cancer (PC) in patients who underwent surgery following atleast one negative prostate biopsy (PB).Materials and methods: A retrospective study of 170 patients who underwent transurethral resection of the prostate (TURP)or open prostatectomy between 1999 and 2007, following one or more negative PB sets. A multivariate logistic regression analysis was carried out in order to determine variables related to the finding of PC. The predictive capacity of PSA, PSA-density and PSA-velocity was assessed by means of ROC curves and the area under the curve (AUC). Sensitivity, specificity and predictive values were determined for several PSA-density and PSA-velocity cut-off points. Results: Open prostatectomy was carried out on 104 patients (61.18%) and TURP on 66 (38.82%). PC was detected in the surgical specimen of 16 patients (9.41%). Variables associated with the finding of PC in the surgical specimen were PSA-density(OR:1.47;95% CI:1.22-6.64; p:0.007) and PSA-velocity (OR:2.87;95% CI:1.60-5.12; p<0.001). The AUCs were 0.746, 0.793 and 0.832, for PSA, PSA-density and PSA-velocity, respectively. The most sensitive PSA-density and PSA-velocity cut-off points indetecting PC were 0.15 and 1ng/ml/year, respectively. Patients without PC showed a median PSA reduction of 9.35 ng/ml (-2.40– 35.40), following surgery. Conclusions: PSA-density and PSA-velocity in particular, allow for the prediction of the presence of PC in the TURP or open prostatectomy specimen of patients with previously negative PBs. Diagnostic TURP could prove useful in patients with clinical suspicion of PC, susceptible to curative treatment, with PSA-velocity >1ng/ml/year and one or more negative saturation biopsies (AU)

MALDI-TOF MS analysis of labile Lolium perenne major allergens in mixes.

BACKGROUND: It is well known that allergen extracts used for specific therapy of allergic disorders are commonly stored as mixtures, causing an alteration of its stability. OBJECTIVE: The aim of this report is to identify pollen allergens susceptible to degradation during storage of mixtures containing different sources of proteases in the absence of glycerol as a preserving agent. METHODS: Mixes containing Lolium perenne (Lol p) pollen extract with either Aspergillus fumigatus or Periplaneta americana extracts were prepared and co-incubated for 90 days at 4 degrees C. Samples were taken off at fixed times and comparatively tested by in vitro and in vivo assays with atopic patients. Selected pollinic allergens were subjected to MALDI-TOF MS analysis. RESULTS: ELISA inhibition evidenced the loss of potency from ryegrass extract, and immunoblotting assays showed the degradation of specific pollinic allergens during storage of mixtures containing protease-rich sources. An in vivo intradermal skin assay confirmed the gradual loss of the biological activity of L. perenne pollen extract co-incubated with non-related protease-rich extracts in comparison with that of the control pollen extract. MALDI-TOF MS analysis allowed us to determine that Lol p 1 and Lol p 5 are susceptible to proteolysis whereas Lol p 4 was found to be resistant to degradation during storage. CONCLUSIONS: Lol p 1 and Lol p 5 degradation is responsible for the loss of the biological activity of L. perenne pollen extract when co-incubated with protease-rich fungal and cockroach extracts in the same vial for months in the absence of glycerol as a preserving agent. The integrity of these major allergens must be preserved to increase the vaccine stability and to assure efficacy when mixes are used for immunotherapy.

Air pollution and seasonal asthma during the pollen season. A cohort study in Puertollano and Ciudad Real (Spain).

BACKGROUND: Many studies have demonstrated a positive association between air pollutants and emergency visits for asthma. However, few studies have included pollen when analysing this relationship in mild-moderate asthmatic patients. OBJECTIVE: To determine the importance of the pollutants such as ozone (O(3)), particles (PM(10)), nitrogen dioxide (NO(2)) and sulphur dioxide (SO(2)) in the clinical course of mild-moderate pollen-allergic asthmatic patients from two Spanish towns in La Mancha: Puertollano (high pollution levels) and Ciudad Real (low pollution levels). METHODS: We used a Poisson regression model to study a cohort of 137 patients from Puertollano and Ciudad Real during two pollen seasons (2000-2001) and analysed the relationship between air pollutant and pollen levels and daily symptoms, the medication used and peak-flow measurements. RESULTS: The number of asthma symptoms and the mean values of the PM(10), SO(2) and NO(2) levels were higher in Puertollano than in Ciudad Real. In Puertollano, the risk of asthma increased by 6% with a 3-day lag for PM(10), by 8% with a 3-day lag for O(3), by 4% with a 1-day lag for SO(2) and by 15% with a 3-day lag for O(3) when its values exceeded the health threshold (P < 0.05). CONCLUSIONS: The air pollution levels in Puertollano were associated with an increased risk of asthma symptoms in pollen-allergic asthmatic patients com pared with a similar group from Ciudad Real.

Hypoxic stimulus alters hypothalamic AMP-activated protein kinase phosphorylation concomitant to hypophagia.

Acute exposure to hypobaric hypoxia is known to decrease food intake, but the molecular mechanisms of such alteration in feeding behavior remain unknown. We tested the hypothesis that hypothalamic AMP-activated protein kinase (AMPK) phosphorylation is affected by acute exposure to hypobaric hypoxia and thus would be involved in initial anorexia. To address this issue, male rats weighing 255-270 g were either submitted to hypobaric hypoxia (H, equivalent altitude of 5,500 m), maintained under local barometric pressure conditions (N), or pair-fed an equivalent quantity of food to that consumed by H rats (PF), for 6, 24, or 48 h. Daily food intake dropped by 73% during the first day of hypoxia (P<0.01) and remained by 46% lower than in N rats thereafter (P<0.01). Hypoxia per se, as estimated by comparing experimental data between the H and PF groups, increased ob gene transcription and plasma leptin concentration. A transient increase in glucose availability occurred in the H group compared with PF animals (P<0.05). The hypoxic stimulus led to an early and transient decrease in hypothalamic AMPK and acetyl-CoA carboxylase (ACC) phosphorylation, concomitant with hypophagia and associated alterations in nutrients and hormones. An increase in NPY mRNA levels occurred from day 1, similarly in H and PF rats, and thus mainly related to food restriction alone (P<0.05). In conclusion, the present study demonstrates that hypoxia per se inhibited AMPK and ACC phosphorylation in the hypothalamus, concomitant with profound anorexia. A powerful counterregulation occurs rapidly, mediated by NPY and devoted to avoid prolonged anorexia.