Comparative bioavailability of cefuroxime axetil suspension formulations administered with food in healthy subjects

Objective: To assess the comparative bioavailability of two formulations (250 mg/5 mL suspension) of cefuroxime axetil (CAS 64544-07-6), administered with food, in healthy volunteers of both sexes. Methods: The study was conducted using an open, randomized, two-period crossover design with a 1-week washout interval. Plasma samples were obtained for up to 12 h post dose. Plasma cefuroxime axetil concentrations were analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS) with negative ion electrospray ionization using multiple reactions monitoring (MRM). From the cefuroxime axetil plasma concentration vs. time curves, the following pharmacokinetic parameters were obtained: AUC(last) and C(max). Results: The limit of quantification was 0.1 mu g/mL for plasma cefuroxime axetil analysis. The geometric mean and 90% confidence interval CI of test/reference product percent ratios were: 106.1% (100.8%-111.8%) for C(max), 109.4% (104.8%-114.2%) for AUC(last). Conclusion: Since the 90% Cl for AUC(last) and C(max) ratios were within the 80-125 % interval proposed by the US FDA, it was concluded that cefuroxime axetil (test formulation, 250 mg/5 mL suspension) was bioequivalent to a reference formulation under fed conditions, for both the rate and extent of absorption.

Autoantibody response to chromatographic fractions from oxidized LDL in unstable angina patients and healthy controls

Levels of autoantibodies to oxidized low-density lipoprotein (oxLDL) have been correlated to atherosclerosis; however, contradictory results have been shown. To better understand the role of autoantibodies to oxLDL in atherogenesis, and their potential to predict risk of developing coronary artery disease we investigated the antibody response of unstable angina (UA) patients and healthy controls against chromatographic separated fractions of oxLDL. Five major peaks were detected after chromatographic separation of oxLDL and 10 fractions were collected. Surprisingly, when the response to high molecular weight fractions was analysed, we observed a significant increase in the levels of autoantibodies in controls compared to UA. In contrast, when the autoantibody response to intermediate and low molecular weight fractions was analysed, we observed that the UA group showed consistently higher levels compared with controls. Our data demonstrates that within oxLDL there are major fractions that can be recognized by autoantibodies from either UA patients or healthy individuals, and that the use of total oxLDL as an antigen pool may mask the presence of some antigenic molecules and their corresponding antibodies. Further studies are needed, but the analysis of antibody profiles may indeed open up a novel approach for evaluation and prevention against atherosclerosis.

Diversity and quantitative analysis of Archaea in aggressive periodontitis and periodontally healthy subjects

P>Aim To investigate the diversity, levels and proportions of Archaea in the subgingival biofilm of generalized aggressive periodontitis (GAgP; n=30) and periodontally healthy (PH; n=30) subjects. Materials and methods Diversity was determined by sequencing archaeal 16S rRNA gene libraries from 20 samples (10/group). The levels and proportions of Archaea were analysed by quantitative PCR (qPCR) in four and two samples/subject in GAgP and PH groups, respectively. Results Archaea were detected in 27/28 subjects and 68% of the sites of the GAgP group, and in 26/30 subjects and 58.3% sites of the PH group. Methanobrevibacter oralis was found in all 20 samples studied, Methanobacterium curvum/congolense in three GAgP and six PH samples, and Methanosarcina mazeii in four samples from each group. The levels and proportions of Archaea were higher in GAgP than in PH, whereas no differences were observed between the two probing depth category sites from the GAgP group. Conclusion Archaea were frequently found in subjects with periodontal health and GAgP, especially M. oralis. However, the higher levels and proportions (Archaea/total prokaryotes) of this domain observed in GAgP in comparison with PH subjects indicate a possible role of some of these microorganisms as an environmental modifier in GAgP.

Shiga toxin-producing Escherichia coli and atypical enteropathogenic Escherichia coli strains isolated from healthy sheep of different populations in Sao Paulo, Brazil

Aims: Sheep are important carriers of Shiga toxin-producing Escherichia coli (STEC) in several countries. However, there are a few reports about ovine STEC in American continent. Methods and Results: About 86 E. coli strains previously isolated from 172 healthy sheep from different farms were studied. PCR was used for detection of stx(1), stx(2), eae, ehxA and saa genes and for the identification of intimin subtypes. Restriction fragment length polymorphism (RFLP)-PCR was performed to investigate the variants of stx(1) and stx(2), and the flagellar antigen (fliC) genes in nonmotile isolates. Five isolates were eae(+) and stx(-), and belonged to serotypes O128:H2/beta-intimin (2), O145:H2/gamma, O153:H7/beta and O178:H7/epsilon. Eighty-one STEC isolates were recovered, and the stx genotypes identified were stx(1c)stx(2d-O118) (46.9%), stx(1c) (27.2%), stx(2d-O118) (23.4%), and stx(1c)stx(2dOX3a) (2.5%). Pulsed-field gel electrophoresis (PFGE) revealed 27 profiles among 53 STEC and atypical enteropathogenic Escherichia coli (EPEC) isolates. Conclusions: This study demonstrated that healthy sheep in Sao Paulo, Brazil, can be carriers of potential human pathogenic STEC and atypical EPEC. Significance and Impact of the Study: As some of the STEC serotypes presently found have been involved with haemolytic uraemic syndrome (HUS) in other countries, the important role of sheep as sources of STEC infection in our settings should not be disregarded.

Chronic exercise decreases cytokine production in healthy rat skeletal muscle

Skeletal muscle is the source of pro- and anti-inflammatory cytokines, and recently, it has been recognized as an important source of interleukin-6 (IL-6). Acute physical exercise is known to induce a pro-inflammatory cytokine profile in the plasma. However, the effect of chronic physical exercise in the production of pro- and anti-inflammatory cytokines by the skeletal muscle has never been examined. We assessed IL-6, TNF-alpha, IL-1 beta and IL-10 levels in the skeletal muscle of rats submitted to endurance training. Animals were randomly assigned to either a Sedentary group (S, n = 7) or an endurance exercise trained group (T, n = 8). Trained rats ran on a treadmill for 5 days week(-1) for 8 weeks (60% VO(2max)). Detection of IL-6, TNF-alpha, IL-1 beta and IL-10 protein expression was carried out by ELISA. We found decreased expression of IL-1 beta, IL-6, TNF-alpha and IL-10 (28%, 27%. 32% and 37%, respectively, p < 0.05) in the extensor digital longus (EDL) from T, when compared with S. In the soleus, IL-1 beta, TNF-alpha and IL-10 protein levels were similarly decreased (34%, 42% and 50%, respectively, p < 0.05) in T in relation to S, while IL-6 expression was not affected by the training protocol. In conclusion, exercise training induced decreased cytokine protein expression in the skeletal muscle. These data show that in healthy rats, 8-week moderate-intensity aerobic training down regulates skeletal muscle production of cytokines involved in the onset, maintenance and regulation of inflammation, and that the response is heterogeneous according to fibre composition. Copyright (C) 2009 John Wiley & Sons, Ltd.

Relative entropy measures applied to healthy and pathological voice characterization

Nowadays, noninvasive methods of diagnosis have increased due to demands of the population that requires fast, simple and painless exams. These methods have become possible because of the growth of technology that provides the necessary means of collecting and processing signals. New methods of analysis have been developed to understand the complexity of voice signals, such as nonlinear dynamics aiming at the exploration of voice signals dynamic nature. The purpose of this paper is to characterize healthy and pathological voice signals with the aid of relative entropy measures. Phase space reconstruction technique is also used as a way to select interesting regions of the signals. Three groups of samples were used, one from healthy individuals and the other two from people with nodule in the vocal fold and Reinke`s edema. All of them are recordings of sustained vowel /a/ from Brazilian Portuguese. The paper shows that nonlinear dynamical methods seem to be a suitable technique for voice signal analysis, due to the chaotic component of the human voice. Relative entropy is well suited due to its sensibility to uncertainties, since the pathologies are characterized by an increase in the signal complexity and unpredictability. The results showed that the pathological groups had higher entropy values in accordance with other vocal acoustic parameters presented. This suggests that these techniques may improve and complement the recent voice analysis methods available for clinicians. (C) 2008 Elsevier Inc. All rights reserved.

Comparative bioavailability of three ibuprofen formulations in healthy human volunteers

Objective: To assess the bioequivalence of three ibuprofen formulations (Test formulation: ibuprofen (400 mg capsule) manufactured by Cardinal Health Brasil 402 Ltda. (Sorocaba, Brazil) and licensed to Boehringer Ingelheim do Brasil Quim. e Farm. Ltda. (Sao Paulo, Brazil); Reference formulation (1): ibuprofen (Advil (R); 2 x 200 mg coated tablet) from Wyeth-Whitehall Ltda. (Itapevi, Brazil); Reference formulation (2): ibuprofen (Alivium (R); 8 ml x 50 mg/ml solution) from Schering Plough S.A. (Rio de Janeiro, Brazil)) in 24 healthy volunteers of both sexes. Methods: The study was conducted using an open, randomized, three-period crossover design with at least 5-day washout interval. Plasma samples were obtained over a 24-h period. Plasma ibuprofen concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) with negative ion electrospray ionization using multiple reaction monitoring (MRM). The following pharmacokinetic parameters were obtained from the ibuprofen plasma concentration vs. time curves: AUC(last), AUC(trunctmax) AUC(inf) and C-max. Results: The limit of quantification for ibuprofen was 0.1 mu g x ml(-1). The geometric mean with corresponding 90% confidence interval (CI) for Test/Reference (1) percent ratios were 114.24% (90% CI = 105.67, 123.50%) for C-max, 98.97% (90% CI = 94.69, 103.44%) for AUC(last) and 99.40% (90% CI = 95.21, 103.78%) for AUCinf. The geometric mean and respective 90% confidence interval (CI) for Test/Reference (2) percent ratios were 108.38% (90% Cl = 100.195, 117.25%) for C-max, 100.79% (90% CI = 96.39, 105.40%) for AUC(last) and 101.26% (90% CI = 96.94, 105.77%) for AUC(inf); t(max) for the 400 mg Test capsule was shorter than that for the 2 x 200 mg Reference (1) tablets (p < 0.002). Conclusion: Since the 90% CI for AUC(last), AUC(inf) and C-max ratios were within the 80 - 125% interval proposed by the US FDA, it was concluded that ibuprofen formulation manufactured by Cardinal Health Brasil 402 Ltda. and licensed to Boehringer Ingelheim do Brasil Quim. e Farm. Ltda. is bioequivalent to the Advil (R) and Alivium (R) formulations with regard to both the rate and the extent of absorption.

Asymmetrical awnings : a way to increase daylight in buildings without increasing the overheating

Different shapes of asymmetric awnings for east and west windows are investigated mathematically as well as by measurement in a model. A box with 90 cm side and a 30x30 cm window was placed outdoor in overcast weather and the daylight factor was measured at the bottom of the box when the window was unshaded or equipped with different awnings. The average daylight factor in the box decreased from 4.6% for the unshaded window to 1.0% when a full awning was used. With “the best” asymmetrical awning, the average daylight factor was 80% larger than with the full awing. Using Dutch climate, calculation of the energy from direct radiation transmitted through the window during the cooling season showed that this was decreased from 100% as an annual mean for the unshaded window down 22% with a full awing. With “the best” asymmetrical awning, 26% of the energy was transmitted. Calculation of the indoor temperature in a hypothetical row house in Netherlands show that the use of either normal or asymmetrical awnings considerable decrease the indoor temperature during the hot season. Therefore the use of asymmetrical awnings for east or west faced windows considerable can increase the daylight in buildings, with almost no change in overheating, compared to if traditional awnings are used.

Energy Efficient Buildings with Functional Steel Cladding

The aim of the study is to develop a model for the energy balance of buildings that includes the effect from the radiation properties of interior and exterior surfaces of the building envelope. As a first step we have used ice arenas as case study objects to investigate the importance of interior low emissivity surfaces. Measurements have been done in two ice arenas in the north part of Sweden, one with lower and one with higher ceiling emissivity. The results show that the low emissivity ceiling gives a much lower radiation temperature interacting with the ice under similar conditions. The dynamic modelling of the roof in ice arenas shows a similar dependence of the roof-to-ice heat flux and the ceiling emissivity.A second part of the study focus on how to realise paints with very low thermal emissivity to be used on interior building surfaces.

Competitive Solar Heating Systems for Residential Buildings (REBUS)

Research on solar combisystems for the Nordic and Baltic countries have been carriedout. The aim was to develop competitive solar combisystems which are attractive tobuyers and to educate experts in the solar heating field.The participants of the projects were the universities: Technical University of Denmark,Dalarna University, University of Oslo, Riga Technical University and Lund Institute ofTechnology, as well as the companies: Metro Therm A/S (Denmark), Velux A/S(Denmark), Solentek AB (Sweden), SolarNor (Norway) and SIA Grandeg (Latvia).The project included education, research, development and demonstration. Theactivities started in 2003 and were finished by the end of 2006. A number of Ph.D.studies in Denmark, Sweden and Latvia, and a post-doc. study in Norway were carriedout. Close cooperation between the researchers and the industry partners ensured thatthe results of the projects can be utilized. The industry partners will soon be able tobring the developed systems into the market.In Denmark and Norway the research and development focused on solarheating/natural gas systems, and in Sweden and Latvia the focus was on solarheating/pellet systems. Additionally, Lund Institute of Technology and University ofOslo studied solar collectors of various types being integrated into the building.

Passive crosslaminated timber buildings : Final report Cerbof-project no. 76

In this project, Stora Enso’s newly developed building system has been further developed to allow building to the Swedish passive house standard for the Swedish climate. The building system is based on a building framework of CLT (Cross laminated timber) boards. The concept has been tested on a small test building. The experience gained from this test building has also been used for planning a larger building (two storeys with the option of a third storey) with passive house standard with this building system. The main conclusions from the project are:  It is possible to build airtight buildings with this technique without using traditional vapour barriers. Initial measurements show that this can be done without reaching critical humidity levels in the walls and roof, at least where wood fibre insulation is used, as this has a greater capacity for storing and evening out the moisture than mineral wool. However, the test building has so far not been exposed to internal generation of moisture (added moisture from showers, food preparation etc.). This needs to be investigated and this will be done during the winter 2013-14.  A new fixing method for doors and windows has been tested without traditional fibre filling between them and the CLT panel. The door or window is pressed directly on to the CLT panel instead, with an expandable sealing strip between them. This has been proved to be successful.  The air tightness between the CLT panels is achieved with expandable sealing strips between the panels. The position of the sealing strips is important, both for the air tightness itself and to allow rational assembly.  Recurrent air tightness measurements show that the air tightness decreased somewhat during the first six months, but not to such an extent that the passive house criteria were not fulfilled. The reason for the decreased air tightness is not clear, but can be due to small movements in the CLT construction and also to the sealing strips being affected by changing outdoor temperatures.  Long term measurements (at least two years) have to be carried out before more reliable conclusions can be drawn regarding the long term effect of the construction on air tightness and humidity in the walls.  An economic analysis comparing using a concrete frame or the studied CLT frame for a three storey building shows that it is probably more expensive to build with CLT. For buildings higher than three floors, the CLT frame has economic advantages, mainly because of the shorter building time compared to using concrete for the frame. In this analysis, no considerations have been taken to differences in the influence on the environment or the global climate between the two construction methods.

Energy efficient and economic renovation of residential buildings with low-temperature heating and air heat recovery

With the building sector accounting for around 40% of the total energy consumption in the EU, energy efficiency in buildings is and continues to be an important issue. Great progress has been made in reducing the energy consumption in new buildings, but the large stock of existing buildings with poor energy performance is probably an even more crucial area of focus. This thesis deals with energy efficiency measures that can be suitable for renovation of existing houses, particularly low-temperature heating systems and ventilation systems with heat recovery. The energy performance, environmental impact and costs are evaluated for a range of system combinations, for small and large houses with various heating demands and for different climates in Europe. The results were derived through simulation with energy calculation tools. Low-temperature heating and air heat recovery were both found to be promising with regard to increasing energy efficiency in European houses. These solutions proved particularly effective in Northern Europe as low-temperature heating and air heat recovery have a greater impact in cold climates and on houses with high heating demands. The performance of heat pumps, both with outdoor air and exhaust air, was seen to improve with low-temperature heating. The choice between an exhaust air heat pump and a ventilation system with heat recovery is likely to depend on case specific conditions, but both choices are more cost-effective and have a lower environmental impact than systems without heat recovery. The advantage of the heat pump is that it can be used all year round, given that it produces DHW. Economic and environmental aspects of energy efficiency measures do not always harmonize. On the one hand, lower costs can sometimes mean larger environmental impact; on the other hand there can be divergence between different environmental aspects. This makes it difficult to define financial subsidies to promote energy efficiency measures.

Policy instruments to improve energy efficiency in buildings

The newly adopted energy efficiency directive (2012/27/EU) highlights the importance of energy efficiency in reaching the Union’s 2020 targets. The directive commits member states to defining national energy efficiency targets (art. 3), achieving yearly energy savings of 1.5% of the annual energy sales through the energy efficiency obligation scheme (art. 7), and providing a long-term strategy for the building sector that aims at a 3% refurbishment rate for public buildings (art. 4+5). Buildings currently account for 40% of energy use in most countries, putting them among the largest end-use sectors. This report takes a closer look at the best practices for implementing increasing energy efficiency in different regions and countries in Europe. The final aim is to identify some policy tools to be suggested to the region of Dalarna (Dalarna having been chosen as the pilot county in Sweden) as a means of implementing energy efficiency in the building sector. The final objective is to give analysts and decision-makers a better analytical foundation to explore future policy development in the area of buildings to be proposed and tested at the regional level in Dalarna and later at the national level in Sweden.

Differences in muscle activity during hand dexterity tasks between women with arthritis and a healthy reference group

Background. Impaired hand function is common in patients with arthritis and it affects performance of daily activities; thus, hand exercises are recommended. There is little information on the extent to which the disease affects activation of the flexor and extensor muscles during these hand-dexterity tasks. The purpose of this study was to compare muscle activation during such tasks in subjects with arthritis and in a healthy reference group. Methods. Muscle activation was measured in m. extensor digitorium communis (EDC) and in m. flexor carpi radialis (FCR) with surface electromyography (EMG) in women with rheumatoid arthritis (RA, n = 20), hand osteoarthritis (HOA, n = 16) and in a healthy reference group (n = 20) during the performance of four daily activity tasks and four hand exercises. Maximal voluntary isometric contraction (MVIC) was measured to enable intermuscular comparisons, and muscle activation is presented as %MVIC. Results. The arthritis group used a higher %MVIC than the reference group in both FCR and EDC when cutting with a pair of scissors, pulling up a zipper and—for the EDC—also when writing with a pen and using a key (p < 0.02). The exercise “rolling dough with flat hands” required the lowest %MVIC and may be less effective in improving muscle strength. Conclusions. Women with arthritis tend to use higher levels of muscle activation in daily tasks than healthy women, and wrist extensors and flexors appear to be equally affected. It is important that hand training programs reflect real-life situations and focus also on extensor strength.