Microemulsions Containing Medium-Chain Glycerides as Transdermal Delivery Systems for Hydrophilic and Hydrophobic Drugs

We evaluated the ability of microemulsions containing medium-chain glycerides as penetration enhancers to increase the transdermal delivery of lipophilic (progesterone) and hydrophilic (adenosine) model drugs as well as the effects of an increase in surfactant blend concentration on drug transdermal delivery. Microemulsions composed of polysorbate 80, medium-chain glycerides, and propylene glycol (1:1:1, w/w/w) as surfactant blend, myvacet oil as the oily phase, and water were developed. Two microemulsions containing different concentrations of surfactant blend but similar water/oil ratios were chosen; ME-lo contained a smaller concentration of surfactant than ME-hi (47:20:33 and 63:14:23 surfactant/oil/water, w/w/w). Although in vitro progesterone and adenosine release from ME-lo and ME-hi was similar, their transdermal delivery was differently affected. ME-lo significantly increased the flux of progesterone and adenosine delivered across porcine ear skin (4-fold or higher, p < 0.05) compared to progesterone solution in oil (0.05 +/- 0.01 mu g/cm(2)/h) or adenosine in water (no drug was detected in the receptor phase). The transdermal flux of adenosine, but not of progesterone, was further increased (2-fold) by ME-hi, suggesting that increases in surfactant concentration represent an interesting strategy to enhance transdermal delivery of hydrophilic, but not of lipophilic, compounds. The relative safety of the microemulsions was assessed in cultured fibroblasts. The cytotoxicity of ME-lo and ME-hi was significantly smaller than sodium lauryl sulfate (considered moderate-to-severe irritant) at same concentrations (up to 50 mu g/mL), but similar to propylene glycol (regarded as safe), suggesting the safety of these formulations.

Pollen abortion rates, nitrogen dioxide by passive diffusive tubes and bioaccumulation in tree barks are effective in the characterization of air pollution

This study aims to evaluate the feasibility of using simple techniques - pollen abortion rates, passive diffusive tubes (NO(2)) and trace element accumulation in tree barks - when determining the area of influence of pollution emissions produced in a traffic corridor. Measurements were performed at 0, 60 and 120 meters from a major road with high vehicular traffic, taking advantage of a sharp gradient that exists between the road and a cemetery. NO(2) values and trace elements measured at 0 meters were significantly higher than those measured at more distant points. Al, S. Cl, V. Fe, Cu, and Zn exhibited a higher concentration in tree barks at the vicinity of the traffic corridor. The same pattern was observed for the pollen abortion rates measured at the three different sites. Our data suggests that simple techniques may be applied either to validate dispersion land-based models in an urban settings or, alternatively, to provide better spatial resolution to air pollution exposure when high-resolution pollution monitoring data are not available. (C) 2011 Elsevier B.V. All rights reserved.

Variability in UVB Tolerances of Melanized and Nonmelanized Cells of Cryptococcus neoformans and C-laurentii

Solar radiation is one of the major factors responsible for the control of fungus populations in the environment. Inactivation by UVA and UVB radiation is especially important for the control of fungi that disperse infective units through the air, including fungi such as Cryptococcus spp. that infect their vertebrate hosts by inhalation. Cryptococcus neoformans produces melanin in the presence of certain exogenous substrates such as l-3,4 dihydroxyphenylalanine and melanization may protect the fungus against biotic and abiotic environmental factors. In the present study, we investigated the effect of exposure to an UVB irradiance of 1000 mW m(-2) (biologically effective weighted irradiance) on the survival of melanized and nonmelanized cells of four strains of C. neoformans and four strains of C. laurentii. The relative survival (survival of cells exposed to radiation in relation to cells not exposed) of cells grown 2, 4, 6 or 8 days on medium with or without L-dopa was determined after exposure to UVB doses of 1.8 and 3.6 kJ m(-2). Both the irradiance spectrum and the intensities of those doses are environmentally realistic, and, in fact, occur routinely during summer months in temperate regions. Differences in tolerance to UVB radiation were observed between the C. neoformans and C. laurentii strains. The C. neoformans strains were more susceptible to UVB radiation than the C. laurentii strains. In C. neoformans, differences in tolerance to radiation were observed during development of both melanized and nonmelanized cells. For most treatments (strain, time of growth and UVB dose), there were virtually no differences in tolerances between melanized and nonmelanized cells, but when differences occurred they were smaller than those previously observed with UVC. In tests with two strains of C. laurentii, there was no difference in tolerance to UVB radiation between melanized and nonmelanized cells during 8 days of culture; and in tests with four strains for less culture time (4 days) there were no significant differences in tolerance between melanized and nonmelanized cells of any strain of this species.

Environmental impact evaluation using a cooperative model for implementing EMS (ISO 14001) in small and medium-sized enterprises

Certification of an ISO 14001 Environmental Management System (EMS) is currently an important requirement for those enterprises wishing to sell their products in the context of a global market. The system`s structure is based on environmental impact evaluation (EIE). However, if an erroneous or inadequate methodology is applied, the entire process may be jeopardized. Many methodologies have been developed for making of EIEs, some of them are fairly complex and unsuitable for EMS implementation in an organizational context, principally when small and medium size enterprises (SMEs) are involved. The proposed methodology for EIE is part of a model for implementing EMS. The methodological approach used was a qualitative exploratory research method based upon sources of evidence such as document analyses, semi-structured interviews and participant observations. By adopting a cooperative implementation model based on the theory of system engineering, difficulties relating to implementation of the sub-system were overcome thus encouraging SMEs to implement EMS. (C) 2007 Elsevier Ltd. All rights reserved.

Systemic Model for Diagnosis of the Micro, Small and Medium Enterprises from Two Cities from the Countryside of the State of So Paulo in Brazil

This article presents a proposal of a systemic model composed for the micro and small companies (MSE) of the region of Ribeiro Preto and the agents which influenced their environment. The proposed model was based on Stafford Beer`s (Diagnosing the system for organizations. Chichester, Wiley, 1985) systemic methodologies VSM (Viable System Model) and on Werner Ulrich`s (1983) CSH (Critical Systems Heuristics). The VSM is a model for the diagnosis of the structure of an organization and of its flows of information through the application of the cybernetics concepts (Narvarte, In El Modelo del Sistema Viable-MSV: experiencias de su aplicacin en Chile. Proyecto Cerebro Colectivo del IAS, Santiago, 2001). On the other hand, CSH focus on the context of the social group applied to the systemic vision as a counterpoint to the organizational management view considered by the VSM. MSE of Ribeiro Preto and Sertozinho had been analyzed as organizations inserted in systems that relate and integrate with other systems concerning the public administration, entities of representation and promotion agencies. The research questions: which are the bonds of interaction among the subsystems in this process and who are the agents involved? The systemic approach not only diagnosed a social group, formed by MSE of Ribeiro Preto and Sertozinho, public authorities and support entities, but could also delineate answers that aimed the clarification of obscure questions generating financial assistance to the formularization of efficient actions for the development of this system.

Electrocatalytic oxidation of ethanol on Sn((1-x))Ir((x))O(2) electrodes in acid medium

The electrochemical oxidation of ethanol at Sn((1-x))Ir (x) O(2) electrodes (with x = 0.01, 0.05, 0.1 and 0.3) was studied in 0.1 mol L(-1) HClO(4) solution. Electrolysis experiments were carried out and the reaction products were analyzed by Liquid Chromatography. It was found that the amounts of the reaction products depended on the composition of the electrode. In situ infrared reflectance spectroscopy measurements were performed to identify the adsorbed intermediates and to postulate a reaction mechanism for ethanol electrooxidation on these electrode materials. As evidence, acetaldehyde and acetic acid were formed through a successive reaction process. Carbon dioxide was also identified as the end product, showing that the cleavage of the carbon-carbon bond occurred. These results indicate that the synthesized catalysts are able to lead to the total combustion of organic compounds. Analysis of the water bending band at different potentials illustrated its role at the electrode interface.

Study of spectroscopic properties of Europium (III) Tris(beta-diketonate) complex and alpha-Cyclodextrin in aqueous medium

The solubilization of an europium (III) beta-diketonate chelate in aqueous medium and the changes in its photophysical properties upon its inclusion into an alpha-cyclodextrin hydrophobic cavity are described. The complex [Eu(tta)(3)center dot(H(2)O)(2)] (tta = 4,4,4-trifluoro-1-(thiophen-2-yl)butane-1,3-dione) was synthesized, characterized, and incorporated into the hydrophobic cavity by stirring in an alpha-cyclodextrin aqueous solution. The inclusion was confirmed by (1)H NMR, and the stoichiometry of association was obtained by the Job method. The maximum in the excitation spectrum of the alpha-CD inclusion compound in aqueous solution was shifted 28 nm compared with the maximum of non alpha-CD complex. The emission spectrum of the association is similar to that of the free solid complex and displays the characteristic (5)D(0) -> (7)F(0-4) Eu(3+) transitions.

Electrochemical degradation of glyphosate formulations at DSA(A (R)) anodes in chloride medium: an AOX formation study

The electrochemical degradation of different glyphosate herbicide formulations on RuO(2) and IrO(2) DSA(A (R)) electrodes is investigated. Parameters that could influence the formation of organochloride compounds during electrolysis are studied. The effects of chloride concentration, electrodic composition, current density, and electrolysis time are reported. The influence of the oxide composition on herbicide degradation seems to be almost insignificant; however, there is a straight relationship between anode composition and organic halides formation. Commercial herbicide formulations have lower degradation rates and lead to the formation of a larger quantities of organochloride compounds. In high chloride concentrations, there is a significant increase in organic mineralization, and the relationship between chloride concentration and organic halides formation is direct. Only in low chloride medium investigated the organochloride concentration obtained was below the limit values allowed in Brazil. The determination of organic halides absorbable (AOX) during electrolysis increases significantly with the applied current. Even during long-term electrolysis, a large amount of organochloride compounds is formed.

Expectation Propagation with Factorizing Distributions: A Gaussian Approximation and Performance Results for Simple Models

We discuss the expectation propagation (EP) algorithm for approximate Bayesian inference using a factorizing posterior approximation. For neural network models, we use a central limit theorem argument to make EP tractable when the number of parameters is large. For two types of models, we show that EP can achieve optimal generalization performance when data are drawn from a simple distribution.

PHRENIC NERVE TRANSFER IN THE RESTORATION OF ELBOW FLEXION IN BRACHIAL PLEXUS AVULSION INJURIES: HOW EFFECTIVE AND SAFE IS IT?

OBJECTIVE: Phrenic nerve transfer has been used for treating lesions of the brachial plexus since 1970. Although, today, surgeons are more experienced with the technique, there are still widespread concerns about its effects on pulmonary function. This study was undertaken to evaluate the effectiveness and safety of this procedure. METHODS: Fourteen patients with complete palsy of the upper limb were submitted to phrenic nerve transfer as part of a strategy for surgical reconstruction of their plexuses. Two patients were lost to follow-up, and 2 patients were followed for less than 2 years. Of the remaining 10 patients, 9 (90%) were male. The lesions affected both sides equally. The mean age of the patients was 24.8 years (range, 14-43 years), and the mean interval from injury to surgery was 6 months (range, 3-9 months). The phrenic nerve was always transferred to the musculocutaneous nerve, and a nerve graft (mean length, 8 cm; range, 4.5-12 cm) was necessary in all cases. RESULTS: There was no major complication related to the surgery. Seven patients (70%) recovered functional level biceps strength (Medical Research Council grade >= 3). All of the patients exhibited a transient decrease in pulmonary function tests, but without clinical respiratory problems. CONCLUSION: On the basis of our small series and data from the literature, we conclude that phrenic nerve transfer in well-selected patients is a safe and effective procedure for recovering biceps function.

Laparoscopic extended cardiomyotomy in children: an effective procedure for the treatment of esophageal achalasia

Purpose: Achalasia of the esophagus is characterized by aperistalsis and incomplete relaxation of the lower esophageal sphincter in response to swallowing. The objective of the present study is to present the experience of a modified Heller myotomy via a laparoscopic approach for the treatment of children who had this condition. Methods: A retrospective review of medical records of all patients who underwent this procedure from 2000 to 2009 was performed. The procedure consisted of an extended esophagomyotomy beginning on the lower part of the lower esophageal sphincter and continuing 5 to 6 cm above on the lower third of the esophagus, and then extended 3 to 4 cm below to the stomach, associated with an anterior 180-degree hemi-fundoplication according to Dor`s technique. Results: Fifteen patients were included in the study. There were 8 female and 7 male patients. Mean operating time was 190 minutes with no intraoperative complications and 1 conversion to open surgery because of difficulty in dissecting an inflamed distal esophagus. In a mean follow-up period of 32.3 months, 2 patients had recurrence of mild dysphagia that disappeared spontaneously, and 1 required a single botulinum toxin injection with complete resolution of symptoms. Conclusion: We conclude that the laparoscopic extended Heller myotomy with Dor fundoplication is a safe and effective method for the treatment for achalasia in the pediatric population even in advanced cases. (C) 2010 Elsevier Inc. All rights reserved.

Peginterferon alfa-2b and Ribavirin: Effective in Patients With Hepatitis C Who Failed Interferon alfa/Ribavirin Therapy

Background & Aims: Treatment with peginterferon alfa and ribavirin produces a sustained virologic response (SVR) in approximately 60% of hepatitis C virus (HCV)-infected patients. Alternate options are needed for patients who relapse or do not respond to therapy. Methods: This prospective, international, multicenter, open-label study evaluated efficacy and safety of peginterferon alfa-2b (1.5 mu g/kg/wk) plus weight-based ribavirin (800-1400 mg/day) in 2333 chronic HCV-infected patients with significant fibrosis/cirrhosis whose previous interferon alfa/ribavirin therapy failed. Patients with undetectable HCV-RNA at treatment week (TW) 12 received 48 weeks of therapy; patients with detectable HCV-RNA at TW12 could enter maintenance studies at TW18; 188 patients with low/detectable HCV-RNA at TW12 continued therapy at the investigator`s request. Results: Overall, 22% of the patients attained SVR (56% with undetectable HCV-RNA and 12% with low/detectable HCV-RNA at TW12). SVR was better in relapsers (38%) than nonresponders (14%), regardless of previous treatment, and in patients previously treated with interferon-alfa/ribavirin (25%) than peginterferon alfa-ribavirin (17%). Predictors of response in patients with undetectable HCV-RNA at TW12 were genotype (2/3 vs 1, respectively; odds ratio [OR] 2.4; P < .0001), fibrosis score (F2 vs F4; OR, 2.2; F3 vs F4; OR, 1.7; P < .0001), and baseline viral load (<= 600,000 vs >600,000 IU/mL; OR, 1.4; P = .0223). These factors plus previous treatment and response were overall predictors of SVR. Safety was similar among fibrosis groups. Conclusions: Peginterferon alfa-2b plus weight-based ribavirin is effective and safe in patients who failed interferon alfa/ribavirin therapy. Genotype, baseline viral load, and fibrosis stage were predictors of response.

Is the combination of mitomycin C, bleomycin and methotrexate effective as a neoadjuvant treatment for cervical cancer in women?

Objective: To determine the effectiveness of the combination of mitomycin C, bleomycin and methotrexate as a neoadjuvant treatment in preparation for surgical treatment of cervical cancer. Methods and Materials: Twenty-seven patients with carcinoma of the uterine cervix (stages exophytic IB2 and IIB-IIIB) who had not previously undergone any treatment received mitomycin C, bleomycin and methotrexate in five sessions, once every four weeks. Results: The objective response rate was approximately 81%, including 16 complete responses and six partial responses. Significant toxic effects were not observed. Responsive patients underwent surgery and remained without evidence of disease for the next 20 years. Unresponsive patients did not fare well and passed away within five years after treatment. Conclusion: Our data suggest that this strategy may be effective for advanced cases, enabling patients to receive surgical treatment.

The need for effective radiosentitizing agents: experience in patients with complete pathological response

Chemoradiation therapy is now considered the preferred initial treatment strategy for distal rectal cancer because of the observation of better local disease control and significant tumor downstaging. Downstaging has become an important clinical outcome as patients with complete pathological response are associated with improved survival. Even though radiation alone may result in low local recurrence rates, the use of additional radiosensitizing agents may provide an increase in local disease control in addition to improved tumor regression rates. Several compounds have been investigated in the setting of neoadjuvant multimodality treatment of rectal cancer with variable rates of treatment-related toxicity and complete pathological response. The balance between complete pathological response and toxicity should aid in the management decision for the use of radiosensitizing agents in the neoadjuvant setting for the treatment of rectal cancer. Anti-Cancer Drugs 22: 308-310 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Is the wearing of elastic stockings for half a day as effective as wearing them for the entire day?

P>Background There is good evidence for the use of compression for some clinical indications but little is known about dosimetry in compression. Objective The aim of this work was to evaluate whether or not the use of compression stockings during part of the day would help in the reduction of evening oedema in patients with clinical, epidemiological, anatomical and physiopathological (CEAP) classifications C0 and C1. Methods The effects of elastic compression stockings on volumetric variations during the working day were evaluated for the legs of two men and 18 women (40 legs). The inclusion criterion was classification as C0 (10 legs) or C1 (30 legs) according to the CEAP criteria. Participants used three-quarter-length elastic compression stockings (20-30 mmHg) on three consecutive days for the entire day or only for the morning or they did not use the stockings at all. Volumetry using the water displacement technique was performed in the morning and in the evening. When the patients wore the stockings only during the morning, volumetry was also performed at 13:00 h. Results Significant increases in volume were observed for both legs when stockings were not used compared with the use of stockings in the morning only. After removing the stockings, both legs had significant increases in volume in the afternoon. However, use for half the day was better than not using the stockings at all. Conclusions The use of elastic compression stockings can reduce volumetric variations during working hours, with the use of stockings for the entire day being better than for just half the day.