Combination of light-driven co-delivery of chemodrugs and plasmonic-induced heat for cancer therapeutics using hybrid protein nanocapsules.

BACKGROUND: Improving the water solubility of hydrophobic drugs, increasing their accumulation in tumor tissue and allowing their simultaneous action by different pathways are essential issues for a successful chemotherapeutic activity in cancer treatment. Considering potential clinical application in the future, it will be promising to achieve such purposes by developing new biocompatible hybrid nanocarriers with multimodal therapeutic activity. RESULTS: We designed and characterised a hybrid nanocarrier based on human serum albumin/chitosan nanoparticles (HSA/chitosan NPs) able to encapsulate free docetaxel (DTX) and doxorubicin-modified gold nanorods (DOXO-GNRs) to simultaneously exploit the complementary chemotherapeutic activities of both antineoplasic compounds together with the plasmonic optical properties of the embedded GNRs for plasmonic-based photothermal therapy (PPTT). DOXO was assembled onto GNR surfaces following a layer-by-layer (LbL) coating strategy, which allowed to partially control its release quasi-independently release regarding DTX under the use of near infrared (NIR)-light laser stimulation of GNRs. In vitro cytotoxicity experiments using triple negative breast MDA-MB-231 cancer cells showed that the developed dual drug encapsulation approach produces a strong synergistic toxic effect to tumoral cells compared to the administration of the combined free drugs; additionally, PPTT enhances the cytostatic efficacy allowing cell toxicities close to 90% after a single low irradiation dose and keeping apoptosis as the main cell death mechanism. CONCLUSIONS: This work demonstrates that by means of a rational design, a single hybrid nanoconstruct can simultaneously supply complementary therapeutic strategies to treat tumors and, in particular, metastatic breast cancers with good results making use of its stimuli-responsiveness as well as its inherent physico-chemical properties.

Curcumin dietary supplementation ameliorates disease phenotype in an animal model of Huntington's disease.

Huntington's disease (HD) has traditionally been described as a disorder purely of the brain; however, evidence indicates that peripheral abnormalities are also commonly seen. Among others, severe unintended body weight loss represents a prevalent and often debilitating feature of HD pathology, with no therapies available. It correlates with disease progression and significantly affects the quality of life of HD patients. Curcumin, a naturally occurring polyphenol with multiple therapeutic properties, has been validated to exert important beneficial effects under health conditions as well as in different pathological settings, including neurodegenerative and gastrointestinal (GI) disorders. Here, we investigated the potential therapeutic action that curcumin-supplemented diet may exert on central and peripheral dysfunctions in R6/2 mice, a well-characterized HD animal model which recapitulates some features of human pathology. Maintenance of normal motor function, protection from neuropathology and from GI dysfunction and preservation of GI emptying and conserved intestinal contractility, proved the beneficial role of life-long dietary curcumin in HD and corroborated the potential of the compound to be exploited to alleviate very debilitating symptoms associated with the disease.

Characterisation of uranium(VI) sorption by two environmental fungal species using gamma spectrometry.

Uranium(VI) sorption by two highly uranium-resistant air-borne fungi in a low-pH medium was measured by means of gamma spectrometry. Growth kinetics and stoichiometry of the two fungal species were also studied. Results show acceptable growth rates in synthetic medium with glucose and ammonia as carbon and nitrogen sources, respectively. Typical oxidative metabolism of carbohydrates was found. In vivo uptake of the radionuclide was negligible, but biosorption dry biomass presented a remarkable performance. The fungal strains showed potential for use in bioremediation.

The effect of physical and chemical properties of swimming pool water and its close environment on the development of contact dermatitis in hydrotherapists.

BACKGROUND: The association between physical and chemical parameters in swimming pool water and the incidence of contact dermatitis (CD) in hydrotherapists was studied. METHODS: Chemical and physical parameters characterizing the water and air environment of swimming pools conducting hydrotherapy program were recorded. Differences between the values of these parameters associated with affected and non-affected hydrotherapists employed in 39 pools were tested statistically. RESULTS: No significant difference was found between the means of each of the physical and chemical parameters associated with the affected and the non-affected group of hydrotherapists. The prevalence ratio of the incidence of CD in pools chlorinated by gaseous chlorine was significantly higher than that in pools disinfected by other forms of chlorine compounds (PR = 1.49, CI = 1.17-1.89, P = 0.017). CONCLUSIONS: Dosing the water with larger amounts of gaseous chlorine compared to other disinfectants and a subsequent temporary decrease in the pH of the water may produce a more aggressive environment. It is suggested that combined effect of the various factors concomitantly with the irritating effect of prolonged exposure to water may trigger CD in pools treated with other chlorine-based compounds.

[Standard error of measurement: an alternative to minimally important difference to access changes in patient-reported-health-outcomes]. / El error estándar de medida: ¿una alternativa a la diferencia mínimamente importante para evaluar cambios en las medidas de salud autopercibida?

OBJECTIVE: To assess the concordance level between the standard Error of Measurement (EEM) and the minimal important difference (MID) criteria when evaluating the magnitude of change in self-perceived health status due to a clinical intervention. METHOD: Two scales of patient self-reported health are used [a measure of benign prostatic hyperplasia impact (BPH-PIM) and a life satisfaction scale (LISAT-8)] in two independent studies carried out in order to adapt each scale to Iberian Spanish population. These studies included 129 and 537 males with benign prostatic hyperplasia (BPH) and erectile dysfunction (ED), respectively. After computing EEM and MID values, patients where classified in three groups attending to each criterion: improvement, without change, and worsening. Cohen s kappa agreement index and Kendall s tau-b lineal correlation coefficient where used to assess the level of concordance between criteria. RESULTS: The concordance level between EEM and MID criteria was found to be high for both scales: kappa agreement index attained values of 0.81 and 0.76, while tau-b correlation coefficient attained values of 0.87 and 0.79. CONCLUSION: The agreement level found allows to state that the EEM criterion is an adequate alternative to the MID criterion when assessing the magnitude of change produced in patient reported health.

Modelling of an oil refinery wastewater treatment plant.

The Activated Sludge Model No. 3 (ASM3) and Dutch calibration guidelines (STOWA) were evaluated in the modelling of an activated sludge system treating effluents from a large oil refinery. The plant was designed to remove suspended solids, organic matter and nitrogen from wastewater at an average water temperature of 34 degrees C. The plant consists of three tanks in series; the first two tanks operate in on-off aeration mode with pure oxygen for N-removal, whilst extra methanol is added for the denitrification, and the third tank is maintained as constantly aerobic. Calibration was performed based on a simplified influent characterisation and extra batch experiments (nitrification and denitrification). With the adjustment of only four parameters the model proved capable of describing the performance of the plant concerning both the liquid phase and the biomass. The model was further used to analyse possible modifications in the plant layout and optimize operational conditions in order to reduce operating costs. Modelling results indicated reduction in methanol dosage by implementing an idle time between aerobic and anoxic phases. In this way, surplus methanol was prevented from entering during the aerobic period. Moreover, simulations showed that the most cost-effective option regarding the denitrification process was a combined pre-post-denitrification scheme, without the need for enlarging existing basins. It can be concluded that although ASM3 and STOWA guidelines were originally developed for domestic wastewater application at a temperature range of 10 to 20 degrees C, they proved well capable of describing the performance of an oil refinery wastewater treatment plant operating at 34 degrees C. Moreover, the plant model proved useful for optimization of the plant performance regarding operational costs.

Self-reported skin disease in hydrotherapists working in swimming pools.

The aim of our study was to investigate the risk and characteristics of self-reported skin diseases among hydrotherapists. We attempted to contact 400 adults who participated in 1 of 2 training courses. 248 were reached and 190 of them (76.6%) completed the questionnaires. The data were collected by means of a telephone interview and a detailed questionnaire sent by mail. Statistical analysis included descriptive statistics, univariate and multifactorial analysis. Of those completing the questionnaire (75.8% females and 24.2% males), 44.4% of the hydrotherapists reported on the development of skin disease for the first time after the beginning of work at the swimming pool. The most common symptoms included pruritus and erythematous patches affecting mainly the extremities and trunk. Both smoking and increased exposure hours to pool water were independently associated with skin disease, suggesting a dose-response relationship. We conclude that contact dermatitis should be recognized as an occupational disease in hydrotherapists.

Estudio comparativo de la eficacia de amlodipino frente a nifedipino GITS en el control de la hipertensión arterial leve-moderada. Seguimiento con monitorización ambulatoria de la presión arterial durante 24 horas / Evaluation of the antihypertensive efficacy of amlodipine versus nifedipine-GITS, using noninvasive 24 hours ambulatory blood pressure monitoring in patients with mild to moderate hypertension

Tras un período de lavado de 2 semanas libre de fármacos y otras 2 semanas de administración de un placebo se han incluido un total de 114 pacientes, mayores de 18 años, diagnosticados de hipertensión arterial (HTA) leve a moderada (presión arterial diastólica [PAD]: 90-119 mmHg). El diseño del estudio fue simple ciego y se comparó la eficacia y tolerancia de amlodipino (AML), con un rango de 5-10 mg en dosis única diaria, frente a nifedipino GITS (NGITS), con un rango de 30-60 mg también en dosis única diaria, durante 2 meses de tratamiento. Se realizaron 2 monitorizaciones de la presión arterial durante 24 horas (MAPA) a cada paciente, una basal, al finalizar la fase placebo, y otra final, transcurridos los 2 meses de tratamiento activo; asimismo para la MAPA final se consideraron 2 subgrupos de pacientes distribuidos aleatoriamente: un subgrupo control o de referencia (incluyendo finalmente 39 MAPA válidos) que tomaron la medicación el día en que se les colocaba la grabadora, y un segundo subgrupo que omitieron la dosis del fármaco correspondiente el día que les era colocado el dispositivo grabador de la MAPA (con 41 MAPA válidos analizados). A cada paciente se le efectuaron controles semanales de la presión arterial (PA), frecuencia cardíaca (FC) y acontecimientos adversos, así como electrocardiograma y analítica (bioquímica y hematimetría) al comienzo y a la finalización del estudio. Se consideró hipertenso, mediante el criterio de a MAPA, todo paciente con una PA media (PAM) en el registro de 24 horas igual o superior a 135 mmHg de PA sistólica (PAS) y 85 mmHg de PAD. El análisis estadístico de los datos se llevó a cabo mediante el protocolo por "intención de tratar" (ITT). Una vez obtenida la MAPA basal, 94 pacientes pasaron a la fase de tratamiento activo, siendo asignados aleatoriamente a alguno de los 2 grupos de tratamiento: 47 fueron incluidos en el grupo de pacientes tratados con AML y 47 fueron incluidos en el grupo tratado con NGITS.La PA, mediante la toma casual, se redujo de 163,3/100,3 a 138,7/87,4 mmHg en el grupo tratado con AML (p < 0,001) y de 163,2/99,7 a 139,9/86 mmHg en el tratado con NGITS (p < 0,001). La FC inicial y final con AML fue de 75,2 y 73,5 lpm, respectivamente (p = 0,128), mientras que con NGITS fue de 76,8 y de 77,2 lpm (p = 0,707), siendo estadísticamente significativas las diferencias entre las FC iniciales obtenidas para cada tratamiento (p = 0,017).No hubo diferencias significativas entre ambos tratamientos en las determinaciones analíticas. Comparando los resultados de la MAPA, para ambos tratamientos y para los subgrupos con y sin omisión de la última dosis se obtuvo que únicamente en el caso de un perfecto cumplimiento terapéutico ambos fármacos reducían de manera similar la PA de los pacientes en el estudio. Sin embargo, cuando se omitió una dosis, el descenso de PAS, PAD y PAM fue superior, en términos absolutos, en los pacientes tratados con AML, siendo, además, estadísticamente significativa la diferencia entre ambos tratamientos en el descenso conseguido de la PAS durante el período nocturno (p = 0,046) (AU)

[Effect of Ispaghula husks on postprandial glycemia in healthy female volunteers]. / Influencia de las cutículas de semillas de Plantago ovata (Ispaghula husk) en la glucemia posprandial en voluntarias sanas.

OBJECTIVES: To evaluate the influence of Ispaghula husk in the postprandial glucose concentrations in serum in healthy volunteers. MATERIAL AND METHODS: This study is divided in two assays and 7 healthy women with ages ranging from 35 to 45 years participated in both assays. Assay 1. Administration of 50 g of glucose dissolved in 125 ml of water (followed by other 150 ml of water). Assay 2. It was carried out one week later in the same women and conditions as assay 1 but adding 10.5 g of Ispaghula husk to the dissolution. In both assays, blood samples were obtained at 0, 10, 20, 30, 45, 60, 75, 90 and 120 minutes after administration and glucose concentration was determined in serum. RESULTS: The value of the area under the mean glucose concentration-time curve obtained in assay 2 (in the presence of fiber) was a 13.6% lower than that obtained in assay 1 (significant difference, p < or = 0.05). Individual concentration-time curves obtained in assay 1 can be considered as normal in 4 of the 7 volunteers. Abnormalities observed in the other 3 curves were due to: her history of prediabetic in one of them (glucose concentration values over 180 mg/100 ml); diabetic patients in her family in other of them (2 values over 180 mg/100 ml) and hypoglycaemia in two of the volunteers. When we administered glucose with fiber in assay 2, in all cases, the maximum concentration reached was lower, the variations in glycaemia values were also lower along the different sampling times (peaks disappear or are less marked) and no hypoglycaemia appeared.

Effect of spironolactone on the renin-aldosterone system in rats.

PRA, PRC and the plasma concentration of aldosterone (Aldo) were measured in rats (Sp-rats) receiving a daily sc injection of Spironolactone, (Sp, 20 mg in olive oil) and in control rats (C-rats) receiving olive oil only. Animals were studied one day after starting treatment, 5 days on treatment or after 5 weeks on the study. PRA, PRC and Aldo were significantly increased in Sp-rats as compared to C-rats throughout all the study. In additional Sp-rats and C-rats, the urine volume, serum Na+ and K+ concentration, Na+ and K+ intake and the urinary excretion of Na+, K+ and aldosterone-18-glucuronide (UAldV) were serially measured during 5 weeks. The total radioactivity plasma clearance after an i.v. bolus injection of 3H-aldosterone was subsequently measured in (5 Sp-rats and 5 C-rats). No significant differences in serum Na+ and K+ concentration and in Na+ and K+ balance were observed between Sp-rats and C-rats. UAldV was significantly higher in Sp-rats than in C-rats during all the study. After 5 weeks on treatment the total radioactivity plasma clearance was significantly higher in Sp-rats than in C-rats. These results indicate that Sp, at high dosage, stimulates renin release and aldosterone secretion by a mechanism unrelated to alterations in Na+ and K+ balance.

J chain is covalently bound to both monomer subunits in human secretory IgA.

Previous work has established that the secretory component (SC) in human secretory IgA is covalently linked to only one of the two IgA monomer subunits, but it has not been clear whether the J chain is covalently linked to one or to both of these subunits. In view of the asymmetry in the disulfide bonding between SC and the IgA subunits, an arrangement which follows disulfide interchange, several models for the disulfide linkage of J chain and the bonds between IgA subunits were envisaged and investigated. When sIgA was gel filtered through Sephadex G-200 in acetic acid, a single major symmetrical peak eluted at the front. This material contained SC, alpha and L chains, and all of the J chain. The greater resolution afforded by polyacrylamide gel electrophoresis in detergent confirmed that human sIgA contains no major noncovalently linked components in the 150,000-200,000 molecular weight range. In another series of experiments the Fc monomer, which is not covalently attached to SC, isolated after treatment of sIgA with IgA protease and cyanogen bromide, was investigated to learn whether alpha chain COOH-terminal octapeptides could be released by reduction. The results were negative. The available data thus favor a model in which J chain is disulfide-bonded to both IgA monomer subunits in sIgA.

Do doctors, nurses, and midwives read?

PIP: Results and recommendations generated by a study of the effectiveness of various types of family planning publications directed at clinic personnel in the Philippines are outlined. Independent variables used in the study were readability and attention-attracting devices of scientific publications about family planning; dependent variables were the extent of reading, sharing of information, and recall among doctors, nurses, and midwives working in clinics. An additional project studying the use of the comic book form in communicating technical information is also reported. It was found that doctors read and remembered the most of all types of publications but did not share the information; nurses who read tended to share, but most did not read; midwives were more likely to read materials in comic book form; and greater readability fostered greater recall among nurses and midwives. Recommendations stemming from this study included stressing the importance of sharing information to clinic staff, presenting technical information in more readable forms, and targeting publications to different types of personnel, as well as conducting more research on how to more effectively disseminate information.^ieng

[Idiopathic intestinal lymphangiectasis. Evolution with M.C.T. (author's transl)]. / Linfangiectasia intestinal idiopática. Evolución con triglicéridos de cadena media

A case of idiopathic intestinal lymphangiectasis is reported in a three month old child. Clinical course and laboratory findings are given in relation to administration of three diets containing different concentrations and types of fat. Short term improvement was only noticed with diets containing low concentrations of long chain triglycerides supplement with medium chain triglycerides. Clinical manifestations related to fat malabsortion improved greatly but there was no relationship with serum protein level. No effect on low level of gamma-globulins and lymphatic displasia was found as sawn in an intestinal biopsy performed after three months of treatment. Nevertheless, long-term results were poor and only were evident in a diminution of steatorrhea and normalization of stools.