Therapeutic armamentarium against systemic fungal infections

ABSTRACTThe incidence of invasive fungal infections (IFIs) has been following an upward trend over time, due to a continuous increase in the number of patients at risk, while the prognosis remains poor. In the last 10 years, the lipidic formulations of amphotericin B, voriconazole and a new family of antifungal drugs, the echinocandins, have been added to the traditional antifungal agents, for decades limited to just a few drugs such as amphotericin B deoxycholate, flucytosine and, later, fluconazole and itraconazole. These additions have improved both the results and the understanding of antifungal therapy, while at the same time making it more complex, with new questions arising that remain to be answered. This article reviews the mechanisms of action, spectrum of activity, pharmacology, administration, adverse effects and indications of each of the antifungal agents currently commercialised for the treatment of IFI

Behaviour during Malolactic Fermentation of Three Strains of Oenococcus oeni Used as Direct Inoculation and Acclimatisation Cultures

The behaviour in malolactic fermentation (MLF) of an autochthonous strain of Oenococcus oeni, C22L9,isolated from a winery in Castilla-La Mancha (Spain), and of two other commercial strains of O. oeni, PN4and Alpha (Lallemand Inc.), inoculated by direct inoculation (MBR®) and after a short acclimatisationphase (1-STEP®), was studied. Strain C22L9 carried out MLF slightly faster than the two other commercialstrains, leading to a lower increase in volatile acidity and in 2,3-butanedione and 3-hydroxy-2-butanoneconcentrations, a higher lactic acid content, lower degradation of citric acid and increased degradation ofethanol. No great differences were observed in the duration of MLF, although the acclimatisation cultureswere slightly faster, or in the composition of the wines when using the O. oeni strains in the form of MBR®or 1-STEP® cultures. The tasters did not detect significant differences in the wines obtained from the samestrain of O. oeni in the two inoculation formats

Optimization of Planck/LFI on--board data handling

To asses stability against 1/f noise, the Low Frequency Instrument (LFI) onboard the Planck mission will acquire data at a rate much higher than the data rate allowed by its telemetry bandwith of 35.5 kbps. The data are processed by an onboard pipeline, followed onground by a reversing step. This paper illustrates the LFI scientific onboard processing to fit the allowed datarate. This is a lossy process tuned by using a set of 5 parameters Naver, r1, r2, q, O for each of the 44 LFI detectors. The paper quantifies the level of distortion introduced by the onboard processing, EpsilonQ, as a function of these parameters. It describes the method of optimizing the onboard processing chain. The tuning procedure is based on a optimization algorithm applied to unprocessed and uncompressed raw data provided either by simulations, prelaunch tests or data taken from LFI operating in diagnostic mode. All the needed optimization steps are performed by an automated tool, OCA2, which ends with optimized parameters and produces a set of statistical indicators, among them the compression rate Cr and EpsilonQ. For Planck/LFI the requirements are Cr = 2.4 and EpsilonQ <= 10% of the rms of the instrumental white noise. To speedup the process an analytical model is developed that is able to extract most of the relevant information on EpsilonQ and Cr as a function of the signal statistics and the processing parameters. This model will be of interest for the instrument data analysis. The method was applied during ground tests when the instrument was operating in conditions representative of flight. Optimized parameters were obtained and the performance has been verified, the required data rate of 35.5 Kbps has been achieved while keeping EpsilonQ at a level of 3.8% of white noise rms well within the requirements.Comment: 51 pages, 13 fig.s, 3 tables, pdflatex, needs JINST.csl, graphicx, txfonts, rotating; Issue 1.0 10 nov 2009; Sub. to JINST 23Jun09, Accepted 10Nov09, Pub.: 29Dec09; This is a preprint, not the final versio

Autologous intramyocardial injection of cultured skeletal muscle-derived stem cells in patients with non-acute myocardial infarction

AIM: Experimental animal studies suggest that the use of skeletal myoblast in patients with myocardial infarction may result in improved cardiac function. The aim of the study was to assess the feasibility and safety of this therapy in patients with myocardial infarction. METHODS AND RESULTS: Twelve patients with old myocardial infarction and ischaemic coronary artery disease underwent treatment with coronary artery bypass surgery and intramyocardial injection of autologous skeletal myoblasts obtained from a muscle biopsy of vastus lateralis and cultured with autologous serum for 3 weeks. Global and regional cardiac function was assessed by 2D and ABD echocardiogram. 18F-FDG and 13N-ammonia PET studies were used to determine perfusion and viability. Left ventricular ejection fraction (LVEF) improved from 35.5+/-2.3% before surgery to 53.5+/-4.98% at 3 months (P=0.002). Echocardiography revealed a marked improvement in regional contractility in those cardiac segments treated with skeletal myoblast (wall motion score index 2.64+/-0.13 at baseline vs 1.64+/-0.16 at 3 months P=0.0001). Quantitative 18F-FDG PET studies showed a significant (P=0.012) increased in cardiac viability in the infarct zone 3 months after surgery. No statistically significant differences were found in 13N-ammonia PET studies. Skeletal myoblast implant was not associated with an increase in adverse events. No cardiac arrhythmias were detected during early follow-up. CONCLUSIONS: In patients with old myocardial infarction, treatment with skeletal myoblast in conjunction with coronary artery bypass is safe and feasible and is associated with an increased global and regional left ventricular function,improvement in the viability of cardiac tissue in the infarct area and no induction of arrhythmias

Characteristics of LPG-diesel dual fuelled engine operated with rapeseed methyl ester and gas-to-liquid diesel fuels

AbstractA Liquefied Petroleum Gas (LPG)-diesel dual fuelled combustion experimental study was carried out to understand the impact of the properties of the direct injection diesel fuels, such as rapeseed methyl ester (RME) and gas-to-liquid (GTL), on combustion characteristics, engine performance and emissions. The experimental results showed that up to 60% of liquid fuel replacement by LPG was reached while keeping engine combustion variability within the acceptable range and obtaining clear benefits in the soot-NOx trade-off. However, the amount of LPG was limited by adverse effects in engine thermal efficiency, HC and CO emissions. LPG–RME showed a good alternative to LPG-diesel dual fuelling, as better engine combustion variability, HC, CO and soot behaviour was obtained when compared to the other liquid fuels, mainly due to its fuel oxygen content. On the other hand, NOx emissions were the highest, but these can be balanced by the application of EGR. LPG–GTL dual fuelling resulted in the highest NOx emissions benefit over a wide range of engine operating conditions. The high cetane number and the absence of aromatic of GTL are the main parameters for the more favourable soot-NOx trade-off compared to LPG–ULSD (ultra low sulphur diesel) dual fuelling