Reversed-phase liquid chromatographic method with fluorescence detection for the simultaneous determination of albendazole sulphoxide, albendazole sulphone and albendazole 2-aminosulphone in sheep plasma

A rapid and sensitive HPLC method for the simultaneous quantification of albendazole sulphoxide (ABZ-SO), albendazole sulphone (ABZ-SO2) and albendazole 2-aminosulphone (ABZ-SO2NH2) in sheep blood plasma has been developed. Plasma samples were extracted with ethyl acetate under alkaline conditions. Separation was achieved on a C18 reversed-phase analytical column, in the presence of positively- (tetra-n-butylammonium hydrogen sulphate) and negatively-charged (octanesulphonate sodium) pairing ions, while detection was performed fluorometrically. Excitation and emission wavelengths were 290 and 320 nm, respectively. Limits of quantification were defined at 39 ng/ml for ABZ-SO, 4.95 ng/ml for ABZ-SO2 and 4 ng/ml for ABZ-SO2NH2. Accuracy data, in terms of recovery efficiency showed overall values (+/- S.E.M.) of 85.6 +/- 1.0% for ABZ-SO, 100.0 +/- 1.0% for ABZ-SO2 and 89.1 +/- 0.6% for ABZ-SO2NH2. The method was successfully applied to quantitatively determine the three albendazole metabolites in plasma samples collected from sheep that had been orally administered albendazole.     

A Predictive Model for Selecting Patients with HCV Genotype 3 Chronic Infection with a High Probability of Sustained Virological Response to Peginterferon Alfa-2a/Ribavirin

Background

Access to direct-acting antiviral agents (DAAs) is restricted in some settings; thus, the European Association for the Study of the Liver recommends dual peginterferon/ribavirin (PegIFN/RBV) therapy wherever DAAs are unavailable. HCV genotype (GT) 3 infection is now the most difficult genotype to eradicate and PegIFN/RBV remains an effective option. The goal of this study was to devise a simple predictive score to identify GT3 patients with a high probability of achieving a sustained virologic response (SVR) with PegIFN alfa-2a/RBV therapy.

Methods

Relationships between baseline characteristics and SVR were explored by multiple logistic regression models and used to develop a simple scoring system to predict SVR using data from 1239 treatment-naive GT3 patients who received PegIFN alfa-2a/RBV for 24 weeks in two large observational cohort studies.

Results

The score was validated using a database of 473 patients. Scores were assigned for six factors as follows: age (years) (≤40: 2 points; >40 but ≤55: 1); bodyweight (kg) (<70: 2; ≥70 but <90: 1); no cirrhosis/transition to cirrhosis (2); ALT ≤2.5 x ULN (1); platelets (10⁹/L) (>200: 2; ≥100 but <200: 1); HCV RNA (<400,000 IU/mL: 1). The points are summed to arrive at a score ranging from 0‒10 where higher scores indicate higher chances of SVR; 141, 123, 203, 249, 232, and 218 patients had total scores of 0‒4, 5, 6, 7, 8, and 9–10, respectively, among whom SVR rates were 45%, 62%, 72%, 76%, 84%, and 89%. Among 622 patients who had scores of 6‒10 and HCV RNA <50 IU/mL by treatment week 4 the SVR rate was 86% (532/622).

Conclusions

A simple baseline scoring system involving age, bodyweight, cirrhosis status, ALT level, platelet count and HCV RNA level can be used to identify treatment-naive Caucasian patients with HCV GT3 infection with a high probability of SVR with PegIFN alfa-2a/RBV therapy.     

Investigation of Biophysical Mechanisms in Gold Nanoparticle Mediated Laser Manipulation of Cells Using a Multimodal Holographic and Fluorescence Imaging Setup

Laser based cell manipulation has proven to be a versatile tool in biomedical applications. In this context, combining weakly focused laser pulses and nanostructures, e.g. gold nanoparticles, promises to be useful for high throughput cell manipulation, such as transfection and photothermal therapy. Interactions between laser pulses and gold nanoparticles are well understood. However, it is still necessary to study cell behavior in gold nanoparticle mediated laser manipulation. While parameters like cell viability or perforation efficiency are commonly addressed, the influence of the manipulation process on other essential cell parameters is not sufficiently investigated yet. Thus, we set out to study four relevant cell properties: cell volume and area, ion exchange and cytoskeleton structure after gold nanoparticle based laser manipulation. For this, we designed a multimodal imaging and manipulation setup. 200 nm gold nanoparticles were attached unspecifically to canine cells and irradiated by weakly focused 850 ps laser pulses. Volume and area change in the first minute post laser manipulation was monitored using digital holography. Calcium imaging and cells expressing a marker for filamentous actin (F-actin) served to analyze the ion exchange and the cytoskeleton, respectively. High radiant exposures led to cells exhibiting a tendency to shrink in volume and area, possibly due to outflow of cytoplasm. An intracellular raise in calcium was observed and accompanied by an intercellular calcium wave. This multimodal approach enabled for the first time a comprehensive analysis of the cell behavior in gold nanoparticle mediated cell manipulation. Additionally, this work can pave the way for a better understanding and the evaluation of new applications in the context of cell transfection or photothermal therapy.     

The relationship between anatomy and photosynthetic performance of heterobaric leaves

Heterobaric leaves show heterogeneous pigmentation due to the occurrence of a network of transparent areas that are created from the bundle sheaths extensions (BSEs). Image analysis showed that the percentage of photosynthetically active leaf area (Ap) of the heterobaric leaves of 31 plant species was species dependent, ranging from 91% in Malva sylvestris to only 48% in Gynerium sp. Although a significant portion of the leaf surface does not correspond to photosynthetic tissue, the photosynthetic capacity of these leaves, expressed per unit of projected area (Pmax), was not considerably affected by the size of their transparent leaf area (At). This means that the photosynthetic capacity expressed per Ap (P*max) should increase with At. Moreover, the expression of P*max could be allowing the interpretation of the photosynthetic performance in relation to some critical anatomical traits. The P*max, irrespective of plant species, correlated with the specific leaf transparent volume (lambda(t)), as well as with the transparent leaf area complexity factor ((CF)A(t)), parameters indicating the volume per unit leaf area and length/density of the transparent tissues, respectively. Moreover, both parameters increased exponentially with leaf thickness, suggesting an essential functional role of BSEs mainly in thick leaves. The results of the present study suggest that although the Ap of an heterobaric leaf is reduced, the photosynthetic performance of each areole is increased, possibly due to the light transferring capacity of BSEs. This mechanism may allow a significant increase in leaf thickness and a consequent increase of the photosynthetic capacity per unit (projected) area, offering adaptive advantages in xerothermic environments.     

Response of greenhouse tomato to salt stress and K+ supplement

Abstract

The effect of NaCl salinity and potassium supplement on growth, tissue ion concentration, photosynthesis, yield and fruit quality characteristics of tomato plants was studied. Tomato plants, hyb. Belladonna, were grown in 8.5 l pots, filled with 1:3 sand:perlite mixture and irrigated with a half-strength Hoagland solution through a closed hydroponic system. Six irrigation treatments were applied, including combinations of 3 salinity (0, 35 and 70 mM NaCl) and two potassium levels (K1: 200 ppm and K2: 400 ppm) in the nutrient solution. Salinity reduced photosynthesis resulting in reduced plant height and dry weight. Yield was reduced by 25% and 69% at 35 and 70 mM, respectively, as compared to control plants (0 mM NaCl). Both total soluble solids and titratable acidity of the fruit increased with increasing salinity and K levels. The application of high potassium level (K2) reduced the concentration of Na and increased that of K in the leaves and roots of the plants, as compared to K1 treatment. Toxicity symptoms were mostly observed in the leaves of 70K1 plants, while no visual symptoms of toxicity were observed in 70K2 treatment. Despite the positive effects of potassium supplement in reducing Na concentration and the absence of toxicity symptoms in the leaves, plant growth was not improved, while leaf photosynthesis was reduced. Furthermore, no positive effects in the percentage of marketable fruit, mean fruit weight and yield were observed in the plants receiving extra K.     

Review: Impact of Helicobacter pylori on Alzheimer's disease: What do we know so far?

Background

Helicobacter pylori has changed radically gastroenterologic world, offering a new concept in patients' management. Over time, more medical data gave rise to diverse distant, extragastric manifestations and interactions of the “new” discovered bacterium. Special interest appeared within the field of neurodegenerative diseases and particularly Alzheimer's disease, as the latter and Helicobacter pylori infection are associated with a large public health burden and Alzheimer's disease ranks as the leading cause of disability. However, the relationship between Helicobacter pylori infection and Alzheimer's disease remains uncertain.

Methods

We performed a narrative review regarding a possible connection between Helicobacter pylori and Alzheimer's disease. All accessible relevant (pre)clinical studies written in English were included. Both affected pathologies were briefly analyzed, and relevant studies are discussed, trying to focus on the possible pathogenetic role of this bacterium in Alzheimer's disease.

Results

Data stemming from both epidemiologic studies and animal experiments seem to be rather encouraging, tending to confirm the hypothesis that Helicobacter pylori infection might influence the course of Alzheimer's disease pleiotropically. Possible main mechanisms may include the bacterium's access to the brain via the oral‐nasal‐olfactory pathway or by circulating monocytes (infected with Helicobacter pylori due to defective autophagy) through disrupted blood‐brain barrier, thereby possibly triggering neurodegeneration.

Conclusions

Current data suggest that Helicobacter pylori infection might influence the pathophysiology of Alzheimer's disease. However, further large‐scale randomized controlled trials are mandatory to clarify a possible favorable effect of Helicobacter pylori eradication on Alzheimer's disease pathophysiology, before the recommendation of short‐term and cost‐effective therapeutic regimens against Helicobacter pylori‐related Alzheimer's disease.     

Cost-Effectiveness of a Specialist Geriatric Medical Intervention for Frail Older People Discharged from Acute Medical Units: Economic Evaluation in a Two-Centre Randomised Controlled Trial (AMIGOS)

BackgroundPoor outcomes and high resource-use are observed for frail older people discharged from acute medical units. A specialist geriatric medical intervention, to facilitate Comprehensive Geriatric Assessment, was developed to reduce the incidence of adverse outcomes and associated high resource-use in this group in the post-discharge period.ObjectiveTo examine the costs and cost-effectiveness of a specialist geriatric medical intervention for frail older people in the 90 days following discharge from an acute medical unit, compared with standard care.MethodsEconomic evaluation was conducted alongside a two-centre randomised controlled trial (AMIGOS). 433 patients (aged 70 or over) at risk of future health problems, discharged from acute medical units within 72 hours of attending hospital, were recruited in two general hospitals in Nottingham and Leicester, UK. Participants were randomised to the intervention, comprising geriatrician assessment in acute units and further specialist management, or to control where patients received no additional intervention over and above standard care. Primary outcome was incremental cost per quality adjusted life year (QALY) gained.ResultsWe undertook cost-effectiveness analysis for 417 patients (intervention: 205). The difference in mean adjusted QALYs gained between groups at 3 months was -0.001 (95% confidence interval [CI]: -0.009, 0.007). Total adjusted secondary and social care costs, including direct costs of the intervention, at 3 months were £4412 (€5624, $6878) and £4110 (€5239, $6408) for the intervention and standard care groups, the incremental cost was £302 (95% CI: 193, 410) [€385, $471]. The intervention was dominated by standard care with probability of 62%, and with 0% probability of cost-effectiveness (at £20,000/QALY threshold).ConclusionsThe specialist geriatric medical intervention for frail older people discharged from acute medical unit was not cost-effective. Further research on designing effective and cost-effective specialist service for frail older people discharged from acute medical units is needed.

Trial Registration

ISRCTN registry ISRCTN21800480 http://www.isrctn.com/ISRCTN21800480