Monte Carlo study for designing a dedicated "D"-shaped collimator used in the external beam radiotherapy of retinoblastoma patients.

PURPOSE: Retinoblastoma is the most common intraocular malignancy in the early childhood. Patients treated with external beam radiotherapy respond very well to the treatment. However, owing to the genotype of children suffering hereditary retinoblastoma, the risk of secondary radio-induced malignancies is high. The University Hospital of Essen has successfully treated these patients on a daily basis during nearly 30 years using a dedicated "D"-shaped collimator. The use of this collimator that delivers a highly conformed small radiation field, gives very good results in the control of the primary tumor as well as in preserving visual function, while it avoids the devastating side effects of deformation of midface bones. The purpose of the present paper is to propose a modified version of the "D"-shaped collimator that reduces even further the irradiation field with the scope to reduce as well the risk of radio-induced secondary malignancies. Concurrently, the new dedicated "D"-shaped collimator must be easier to build and at the same time produces dose distributions that only differ on the field size with respect to the dose distributions obtained by the current collimator in use. The scope of the former requirement is to facilitate the employment of the authors' irradiation technique both at the authors' and at other hospitals. The fulfillment of the latter allows the authors to continue using the clinical experience gained in more than 30 years. METHODS: The Monte Carlo code PENELOPE was used to study the effect that the different structural elements of the dedicated "D"-shaped collimator have on the absorbed dose distribution. To perform this study, the radiation transport through a Varian Clinac 2100 C/D operating at 6 MV was simulated in order to tally phase-space files which were then used as radiation sources to simulate the considered collimators and the subsequent dose distributions. With the knowledge gained in that study, a new, simpler, "D"-shaped collimator is proposed. RESULTS: The proposed collimator delivers a dose distribution which is 2.4 cm wide along the inferior-superior direction of the eyeball. This width is 0.3 cm narrower than that of the dose distribution obtained with the collimator currently in clinical use. The other relevant characteristics of the dose distribution obtained with the new collimator, namely, depth doses at clinically relevant positions, penumbrae width, and shape of the lateral profiles, are statistically compatible with the results obtained for the collimator currently in use. CONCLUSIONS: The smaller field size delivered by the proposed collimator still fully covers the planning target volume with at least 95% of the maximum dose at a depth of 2 cm and provides a safety margin of 0.2 cm, so ensuring an adequate treatment while reducing the irradiated volume.

Influence of penetration enhancers and molecular weight in antifungals permeation through bovine hoof membranes and prediction of efficacy in human nails.

This work aimed to evaluate the effect of different substances on the permeation of geraniol through bovine hoof membranes. Different penetration enhancers were able to increase the permeability up to 25 times compared to control. It was demonstrated that acetilcysteine in association with ascorbic acid increased the permeation, even in acid formulations. In addition, some antifungal drugs were incorporated into a gel formulation of HPMC containing acetylcysteine 5% and ascorbic acid 0.2% and then the permeation coefficient through bovine hoof membranes was evaluated. The relationship between permeability and molecular weight was established for fluconazole, miconazole, terbinafine, butenafine, geraniol and nerol. Geraniol and nerol, the antifungals with lower molecular weight, had the better permeability results. Permeability coefficients for nail plates were estimated and geraniol demonstrated similar or even better efficacy index values against T. rubrum, T. menthagrophytes and M. canis compared with terbinafine and miconazole.

Retinoblastoma external beam photon irradiation with a special 'D'-shaped collimator: a comparison between measurements, Monte Carlo simulation and a treatment planning system calculation.

Retinoblastoma is the most common eye tumour in childhood. According to the available long-term data, the best outcome regarding tumour control and visual function has been reached by external beam radiotherapy. The benefits of the treatment are, however, jeopardized by a high incidence of radiation-induced secondary malignancies and the fact that irradiated bones grow asymmetrically. In order to better exploit the advantages of external beam radiotherapy, it is necessary to improve current techniques by reducing the irradiated volume and minimizing the dose to the facial bones. To this end, dose measurements and simulated data in a water phantom are essential. A Varian Clinac 2100 C/D operating at 6 MV is used in conjunction with a dedicated collimator for the retinoblastoma treatment. This collimator conforms a 'D'-shaped off-axis field whose irradiated area can be either 5.2 or 3.1 cm(2). Depth dose distributions and lateral profiles were experimentally measured. Experimental results were compared with Monte Carlo simulations' run with the penelope code and with calculations performed with the analytical anisotropic algorithm implemented in the Eclipse treatment planning system using the gamma test. penelope simulations agree reasonably well with the experimental data with discrepancies in the dose profiles less than 3 mm of distance to agreement and 3% of dose. Discrepancies between the results found with the analytical anisotropic algorithm and the experimental data reach 3 mm and 6%. Although the discrepancies between the results obtained with the analytical anisotropic algorithm and the experimental data are notable, it is possible to consider this algorithm for routine treatment planning of retinoblastoma patients, provided the limitations of the algorithm are known and taken into account by the medical physicist and the clinician. Monte Carlo simulation is essential for knowing these limitations. Monte Carlo simulation is required for optimizing the treatment technique and the dedicated collimator.

Modified classification of normal lung sounds applying Quantile vectors.

In this paper a novel Lung Sound Automatic Verification (LSAV) system and front-end Quantile based acoustic models to classify Lung Sounds (LS) are proposed. The utilization of Quantiles allowed an easier and objective assessment with smaller computational demand. Moreover, less-complex Gaussian Mixture Models (GMM) were computed than those previously reported. The LSAV system allowed us to reach practically negligible error in healthy (normal) LS verification. LASV system efficiency and the optimal GMM's were evaluated by using Equal Error Rate (EER) and Bayesian Information Criterion (BIC) techniques respectively. These approaches could provide a tool for broader medical evaluation which does not rely, as it is often the case, on a qualitative and subjective description of LS.

Acoustics based assessment of respiratory diseases using GMM classification.

The focus of this paper is to present a method utilizing lung sounds for a quantitative assessment of patient health as it relates to respiratory disorders. In order to accomplish this, applicable traditional techniques within the speech processing domain were utilized to evaluate lung sounds obtained with a digital stethoscope. Traditional methods utilized in the evaluation of asthma involve auscultation and spirometry, but utilization of more sensitive electronic stethoscopes, which are currently available, and application of quantitative signal analysis methods offer opportunities of improved diagnosis. In particular we propose an acoustic evaluation methodology based on the Gaussian Mixed Models (GMM) which should assist in broader analysis, identification, and diagnosis of asthma based on the frequency domain analysis of wheezing and crackles.

Impact of irrigation with arsenic-rich groundwater on soils and crops.

The study was carried out in an intensively cultivated agricultural area of central Spain where high arsenic (As) concentrations in groundwater were previously reported. The concentrations and distribution of As in soils and crops (wheat, potato, sugar beet and carrot) were determined to know the effect of irrigation with As-rich groundwater in the agricultural fields, and to estimate its impact on the food chain contamination. Irrigation water shows high As concentrations ranging between 38 and 136 microg/l. Total As contents in the studied agricultural soils are higher than 10 mg/kg exceeding the As content in two control areas and the results of this study reflect that irrigation with As-rich groundwater led to the elevated As levels in the agricultural soils. Total As concentration in soils of a sugar beet plot (36 mg/kg) is higher than that found in soils of the less intensively watered field (11 mg/kg), and more than 3.5 times higher than that in the soils of the control area irrigated with uncontaminated water (<10 mg/kg). Water soluble As in soils ranges between 0.03 and 0.9 mg/kg exceeding the limit of 0.04 mg/kg for agricultural use and shows a significant correlation with total As and organic matter (OM) content in soils. Arsenic contents in potato tuber samples are 35 times higher than that measured in potato tuber of uncontaminated control sites (0.03 mg/kg). Elevated As contents (3.9-5.4 mg/kg DW) were also found in root samples of sugar beet. The As contents in vegetable samples are higher than As content (0.1 mg/kg DW) in plants of uncontaminated control areas, and the limits for foodstuffs (0.5-1 mg/kg DW) set by legislation of many countries reflecting the risk of food chain contamination by As in this study area.

Development of topical nanoemulsions containing the isoflavone genistein.

We have recently described the incorporation of genistein into topical nanoemulsions. This study describes the physicochemical properties and the genistein permeation profile from these nanoemulsions. Formulations composed of egg lecithin, medium chain triglycerides (MCT) or octyldodecanol (ODD) and water were prepared by spontaneous emulsification. Irrespective of the oil core employed (MCT or ODD), this procedure yielded monodisperse emulsions with mean droplet sizes in the range of 230-280 nm. The addition of genistein in the oil phase, before emulsification, did not alter the properties of nanoemulsions. The amount of genistein incorporated in both formulations was close to 100% (1 mg/mL). Solubility and DSC experiments suggested that egg-lecithin may play an important role on the incorporation of genistein in nanoemulsions. Genistein permeation from formulations was assessed using pig ear skin in Franz type diffusion cells. The overall results showed a slow permeation profile for genistein from both nanoemulsions.Such results open interesting perspectives for the topical administration of genistein.

Solid state evaluation of some thalidomide raw materials.

Thalidomide presents polymorphism and is a problematic drug due to its poor solubility and difficult tablet processability, which is the dosage form available in Brazil. In most cases, the pharmacopoeias specify do not address solid state characterization of drugs precisely. In this work, different thalidomide commercial samples were characterized by infrared spectroscopy, particle size analysis, scanning electron microscopy, and X-ray diffraction. In addition, the polymorphic forms were quantified for Rietveld analysis and their intrinsic dissolution rates were evaluated. The results demonstrated the market availability of different raw materials which lack of homogeneity due to differences related to crystalline constitution, crystal habit and intrinsic dissolution rate.

Development and validation of a LC method for determination of genistein in topical nanoemulsions.

The aim of this study was to develop and validate an isocratic LC method for the quantification of genistein in topical nanoemulsions. The analyses were performed at room temperature on a reversed-phase C18 column using a mobile phase composed of methanol/water/acetonitrile (70:25:5, w/w/w) at 1.0 ml x min(-1). The detection was carried out on a UV detector at 327 nm. The linearity, in the range of 25-75 microg/ml, presented a determination coefficient (r2) higher than 0.999, calculated by the least square method. No interferences from the excipients (egg-lecithin, octyldodecanol or medium chain triglycerides) were detected. The R.S.D. values for intra- and inter-day precision experiments were lower than 2.3%. The recovery of genistein from nanoemulsions ranged from 96.6% to 106.6%. The excellent performance of the method, its linearity, accuracy and precision, demonstrate that it can be readily used to quantify genistein incorporated in nanoemulsions.

Carbamazepine/betaCD/HPMC solid dispersions. II. Physical characterization.

Solid dispersions containing carbamazepine (CBZ) associated with beta-cyclodextrin (betaCD) and/or hydroxypropyl methylcellulose were prepared by two different methods, spray-drying or physical mixture, and characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), infrared (IR) spectroscopy, and x-ray powder diffraction analysis (XRPD) studies. Scanning electron microscopy pictures showed that spray-drying produced a mixture of hollow, spherical, and partially shrunken microparticles of homogeneous materials, whereas the physical mixtures yielded heterogeneous systems in which all individual components could be identified. Thermal and IR analyses suggest the existence of a strong interaction between CBZ and excipients in spray-dried solid dispersions, but no CBZ polymorphic transition was detected by either IR spectroscopy or XRPD analysis after the spray-drying process.

Rodent malaria prophylaxis by transdermal delivery of primaquine.

The efficacy of a new transdermal delivery system of primaquine in order to obtain causal prophylaxis against sporozoite-induced Plasmodium yoelii infection was evaluated. A single administration of a 1.0 cm2 transdermal delivery system containing 5.0 mg of primaquine was able to protect 100% of treated mice. This result suggests that the transdermal route may be a very interesting approach for malaria prophylaxis and should encourage further studies in order to determine the absolute bioavailability of the drug as well as its dose-effect relationship.

Role of Organic Acids in the Manganese-Independent Biobleaching System of Bjerkandera sp. Strain BOS55

Bjerkandera sp. strain BOS55 is a white rot fungus that can bleach EDTA-extracted eucalyptus oxygen-delignified kraft pulp (OKP) without any requirement for manganese. Under manganese-free conditions, additions of simple physiological organic acids (e.g., glycolate, glyoxylate, oxalate, and others) at 1 to 5 mM stimulated brightness gains and pulp delignification two- to threefold compared to results for control cultures not receiving acids. The role of the organic acids in improving the manganese-independent biobleaching was shown not to be due to pH-buffering effects. Instead, the stimulation was attributed to enhanced production of manganese peroxidase (MnP) and lignin peroxidase (LiP) as well as increased physiological concentrations of veratryl alcohol and oxalate. These factors contributed to greatly improved production of superoxide anion radicals, which may have accounted for the more extensive biobleaching. Optimum biobleaching corresponded most to the production of MnP. These results suggest that MnP from Bjerkandera is purposefully produced in the absence of manganese and can possibly function independently of manganese in OKP delignification. LiP probably also contributed to OKP delignification when it was present.

Preliminary evaluation of primaquine activity on rodent malaria model after transdermal administration.

The aim of this preliminary study was to investigate the potential use of the transdermal route for primaquine administration in the treatment of malaria. Thus the activity of this drug on asexual blood forms of two rodent malaria parasites (P. v. petteri and P. y. nigeriensis) was evaluated following a single TTS patch application. Sustained plasma concentration values were observed for about 60 hours. The results obtained from a prepatency test showed that primaquine was more active towards P. v. petteri than P. y. nigeriensis. This preliminary study showed that the transdermal route for primaquine administration may be a promising strategy for improving the treatment of malaria in both causal prophylactic and prevention of relapses infection.

Tratamiento de la hipertensión arterial en la diabetes mellitus / Treatment of hypertension in diabetes mellitus

Se presenta una revisión sobre hipertensión arterial en diabetes mellitus, abordando aspectos tales como su prevalencia, situación fisiopatológica, efectos colaterales de la medicación antihipertensiva, la individualización y generalización del tratamiento y la hipertensión arterial en la nefropatía diabética. Se acompaña una guía de aplicación terapéutica

Tratamiento de la hipertensión arterial en la diabetes mellitus / Treatment of hypertension in diabetes mellitus

Se presenta una revisión sobre hipertensión arterial en diabetes mellitus, abordando aspectos tales como su prevalencia, situación fisiopatológica, efectos colaterales de la medicación antihipertensiva, la individualización y generalización del tratamiento y la hipertensión arterial en la nefropatía diabética. Se acompaña una guía de aplicación terapéutica (AU)