Synergistic Effect between Amoxicillin and TLR Ligands on Dendritic Cells from Amoxicillin-Delayed Allergic Patients.

Amoxicillin, a low-molecular-weight compound, is able to interact with dendritic cells inducing semi-maturation in vitro. Specific antigens and TLR ligands can synergistically interact with dendritic cells (DC), leading to complete maturation and more efficient T-cell stimulation. The aim of the study was to evaluate the synergistic effect of amoxicillin and the TLR2, 4 and 7/8 agonists (PAM, LPS and R848, respectively) in TLR expression, DC maturation and specific T-cell response in patients with delayed-type hypersensitivity (DTH) reactions to amoxicillin. Monocyte-derived DC from 15 patients with DTH to amoxicillin and 15 controls were cultured with amoxicillin in the presence or absence of TLR2, 4 and 7/8 agonists (PAM, LPS and R848, respectively). We studied TLR1-9 gene expression by RT-qPCR, and DC maturation, lymphocyte proliferation and cytokine production by flow cytometry. DC from both patients and controls expressed all TLRs except TLR9. The amoxicillin plus TLR2/4 or TLR7/8 ligands showed significant differences, mainly in patients: AX+PAM+LPS induced a decrease in TLR2 and AX+R848 in TLR2, 4, 7 and 8 mRNA levels. AX+PAM+LPS significantly increased the percentage of maturation in patients (75%) vs. controls (40%) (p=0.036) and T-cell proliferation (80.7% vs. 27.3% of cases; p=0.001). Moreover, the combinations AX+PAM+LPS and AX+R848 produced a significant increase in IL-12p70 during both DC maturation and T-cell proliferation. These results indicate that in amoxicillin-induced maculopapular exanthema, the presence of different TLR agonists could be critical for the induction of the innate and adaptive immune responses and this should be taken into account when evaluating allergic reactions to these drugs.

Bioactive endophytic fungi isolated from Caesalpinia echinata Lam. (Brazilwood) and identification of beauvericin as a trypanocidal metabolite from Fusarium sp.

Aiming to identify new sources of bioactive secondary metabolites, we isolated 82 endophytic fungi from stems and barks of the native Brazilian tree Caesalpinia echinata Lam. (Fabaceae). We tested their ethyl acetate extracts in several in vitro assays. The organic extracts from three isolates showed antibacterial activity against Staphylococcus aureus and Escherichia coli [minimal inhibitory concentration (MIC) 32-64 μg/mL]. One isolate inhibited the growth of Salmonella typhimurium (MIC 64 μg/mL) and two isolates inhibited the growth of Klebsiella oxytoca (MIC 64 μg/mL), Candida albicans and Candida tropicalis (MIC 64-128 μg/mL). Fourteen extracts at a concentration of 20 μg/mL showed antitumour activities against human breast cancer and human renal cancer cells, while two isolates showed anti-tumour activities against human melanoma cancer cells. Six extracts were able to reduce the proliferation of human peripheral blood mononuclear cells, indicating some degree of selective toxicity. Four isolates were able to inhibit Leishmania (Leishmania) amazonensis and one isolate inhibited Trypanosoma cruzi by at least 40% at 20 μg/mL. The trypanocidal extract obtained from Fusarium sp. [KF611679] culture was subjected to bioguided fractionation, which revealed beauvericin as the compound responsible for the observed toxicity of Fusarium sp. to T. cruzi. This depsipeptide showed a half maximal inhibitory concentration of 1.9 μg/mL (2.43 μM) in a T. cruzi cellular culture assay.

Adipose tissue concentrations of persistent organic pollutants and total cancer risk in an adult cohort from Southern Spain: preliminary data from year 9 of the follow-up.

There is an increasing trend in the incidence of cancer worldwide, and it has been accepted that environmental factors account for an important proportion of the global burden. The present paper reports preliminary findings on the influence of the historical exposure to a group of persistent organic pollutants on total cancer risk, at year 9 in the follow-up of a cohort from Southern Spain. A cohort of 368 participants (median age 51 years) was recruited in 2003. Their historical exposure was estimated by analyzing residues of persistent organic pollutants in adipose tissue. Estimation of cancer incidence was based on data from a population-based cancer registry. Statistical analyses were performed using multivariable Cox-regression models. In males, PCB 153 concentrations were positively associated with total cancer risk, with an adjusted hazard ratio (95% confidence interval) of 1.20 (1.01-1.41) for an increment of 100 ng/g lipid. Our preliminary findings suggest a potential relationship between the historical exposure to persistent organic pollutants and the risk of cancer in men. However, these results should be interpreted with caution and require verification during the future follow-up of this cohort.

An in vitro iron superoxide dismutase inhibitor decreases the parasitemia levels of Trypanosoma cruzi in BALB/c mouse model during acute phase.

In order to identify new compounds to treat Chagas disease during the acute phase with higher activity and lower toxicity than the reference drug benznidazole (Bz), two hydroxyphthalazine derivative compounds were prepared and their trypanocidal effects against Trypanosoma cruzi were evaluated by light microscopy through the determination of IC50 values. Cytotoxicity was determined by flow cytometry assays against Vero cells. In vivo assays were performed in BALB/c mice, in which the parasitemia levels were quantified by fresh blood examination; the assignment of a cure was determined by reactivation of blood parasitemia levels after immunosuppression. The mechanism of action was elucidated at metabolic and ultra-structural levels, by (1)H NMR and TEM studies. Finally, as these compounds are potentially capable of causing oxidative damage in the parasites, the study was completed, by assessing their activity as potential iron superoxide dismutase (Fe-SOD) inhibitors. High-selectivity indices observed in vitro were the basis of promoting one of the tested compounds to in vivo assays. The tests on the murine model for the acute phase of Chagas disease showed better parasitemia inhibition values than those found for Bz. Compound 2 induced a remarkable decrease in the reactivation of parasitemia after immunosuppression. Compound 2 turned out to be a great inhibitor of Fe-SOD. The high antiparasitic activity and low toxicity together with the modest costs for the starting materials render this compound an appropriate molecule for the development of an affordable anti-Chagas agent.

Chemical analyses of organic residues in archaeological pottery from Arbon Bleiche 3, Switzerland - evidence for dairying in the late Neolithic

Fatty acids distribution and stable isotope ratios (bulk delta(13)C. delta(15)N and delta(13)C of individual fatty acids) of organic residues from 30 potsherds have been used to get further insights into the diet at the Late Neolithic (3384-3370 BC) site of Arbon Bleiche 3. Switzerland. The results are compared with modern equivalents of animal and vegetable fats, which may have been consumed ill a mixed ecology community having agrarian, breeding, shepherd, gathering, hunting, and fishing activities. The used combined chemical and isotopic approach provides valuable information to complement archaeological indirect evidence about the dietary trends obtained from the analysis of faunal and plant remains. The small variations of the delta(13)C and delta(15)N values within the range expected for degraded animal and plant tissues, is consistent with the archaeological evidence of animals, whose subsistence was mainly based on C(3) plants. The overall fatty acid composition and the stable carbon isotopic compositions of palmitic, stearic and oleic acids of the organic residues indicate that the studied Arbon Bleiche 3 sherds contain fat residues of plant and animal origin, most likely ruminant (bovine and ovine). In several vessels the presence of milk residues provides direct evidence for dairying during the late Neolithic in central Europe. (c) 2005 Elsevier Ltd. All rights reserved.

Basis set and electron correlation effects on initial convergence for vibrational nonlinear optical properties of conjugated organic molecules

The level of ab initio theory which is necessary to compute reliable values for the static and dynamic (hyper)polarizabilities of three medium size π-conjugated organic nonlinear optical (NLO) molecules is investigated. With the employment of field-induced coordinates in combination with a finite field procedure, the calculations were made possible. It is stated that to obtain reasonable values for the various individual contributions to the (hyper)polarizability, it is necessary to include electron correlation. Based on the results, the convergence of the usual perturbation treatment for vibrational anharmonicity was examined

δ 15N measurement of organic and inorganic substances by EA-IRMS: a speciation-dependent procedure

Little attention has been paid so far to the influence of the chemical nature of the substance when measuring δ 15N by elemental analysis (EA)-isotope ratio mass spectrometry (IRMS). Although the bulk nitrogen isotope analysis of organic material is not to be questioned, literature from different disciplines using IRMS provides hints that the quantitative conversion of nitrate into nitrogen presents difficulties. We observed abnormal series of δ 15N values of laboratory standards and nitrates. These unexpected results were shown to be related to the tailing of the nitrogen peak of nitrate-containing compounds. A series of experiments were set up to investigate the cause of this phenomenon, using ammonium nitrate (NH4NO3) and potassium nitrate (KNO3) samples, two organic laboratory standards as well as the international secondary reference materials IAEA-N1, IAEA-N2-two ammonium sulphates [(NH4)2SO4]-and IAEA-NO-3, a potassium nitrate. In experiment 1, we used graphite and vanadium pentoxide (V2O5) as additives to observe if they could enhance the decomposition (combustion) of nitrates. In experiment 2, we tested another elemental analyser configuration including an additional section of reduced copper in order to see whether or not the tailing could originate from an incomplete reduction process. Finally, we modified several parameters of the method and observed their influence on the peak shape, δ 15N value and nitrogen content in weight percent of nitrogen of the target substances. We found the best results using mere thermal decomposition in helium, under exclusion of any oxygen. We show that the analytical procedure used for organic samples should not be used for nitrates because of their different chemical nature. We present the best performance given one set of sample introduction parameters for the analysis of nitrates, as well as for the ammonium sulphate IAEA-N1 and IAEA-N2 reference materials. We discuss these results considering the thermochemistry of the substances and the analytical technique itself. The results emphasise the difference in chemical nature of inorganic and organic samples, which necessarily involves distinct thermochemistry when analysed by EA-IRMS. Therefore, they should not be processed using the same analytical procedure. This clearly impacts on the way international secondary reference materials should be used for the calibration of organic laboratory standards.

Tillage Management and Soil Organic Matter, 2005

Tillage systems play a significant role in agricultural production throughout Iowa and the Midwest. It has been well documented that increased tillage intensities can reduce soil organic matter in the topsoil due to increased microbial activity and carbon (C ) oxidation. The potential loss of soil organic matter due to tillage operations is much higher for high organic matter soils than low organic matter soils. Tillage effects on soil organic matter can be magnified through soil erosion and loss of soil productivity. Soil organic matter is a natural reservoir for nutrients, buffers against soil erosion, and improves the soil environment to sustain soil productivity. Maintaining soil productivity requires an agriculture management system that maintains or improves soil organic matter content. Combining cropping systems and conservation tillage practices, such as no-tillage, strip-tillage, or ridge-tillage, are proven to be very effective in improving soil organic matter and soil quality.

On the Segregation of Genetically Modified, Conventional, and Organic Products in European Agriculture: A Multi-market Equilibrium Analysis, October 2005

Evaluating the possible benefits of the introduction of genetically modified (GM) crops must address the issue of consumer resistance as well as the complex regulation that has ensued. In the European Union (EU) this regulation envisions the “co-existence” of GM food with conventional and quality-enhanced products, mandates the labelling and traceability of GM products, and allows only a stringent adventitious presence of GM content in other products. All these elements are brought together within a partial equilibrium model of the EU agricultural food sector. The model comprises conventional, GM and organic food. Demand is modelled in a novel fashion, whereby organic and conventional products are treated as horizontally differentiated but GM products are vertically differentiated (weakly inferior) relative to conventional ones. Supply accounts explicitly for the land constraint at the sector level and for the need for additional resources to produce organic food. Model calibration and simulation allow insights into the qualitative and quantitative effects of the large-scale introduction of GM products in the EU market. We find that the introduction of GM food reduces overall EU welfare, mostly because of the associated need for costly segregation of non-GM products, but the producers of quality-enhanced products actually benefit.

Mutism and Amnesia following High-Voltage Electrical Injury: Psychogenic Symptomatology Triggered by Organic Dysfunction?

Background: Mutism and dense retrograde amnesia are found both in organic and dissociative contexts. Moreover, dissociative symptoms may be modulated by right prefrontal activity. A single case, M.R., developed left hemiparesis, mutism and retrograde amnesia after a high-voltage electric shock without evidence of lasting brain lesions. M.R. suddenly recovered from his mutism following a mild brain trauma 2 years later. Methods: M.R.'s neuropsychological pattern and anatomoclinical correlations were studied through (i) language and memory assessment to characterize his deficits, (ii) functional neuroimaging during a standard language paradigm, and (iii) assessment of frontal and left insular connectivity through diffusion tractography imaging and transcranial magnetic stimulation. A control evaluation was repeated after recovery. Findings: M.R. recovered from the left hemiparesis within 90 days of the accident, which indicated a transient right brain impairment. One year later, neurobehavioral, language and memory evaluations strongly suggested a dissociative component in the mutism and retrograde amnesia. Investigations (including MRI, fMRI, diffusion tensor imaging, EEG and r-TMS) were normal. Twenty-seven months after the electrical injury, M.R. had a very mild head injury which was followed by a rapid recovery of speech. However, the retrograde amnesia persisted. Discussion: This case indicates an interaction of both organic and dissociative mechanisms in order to explain the patient's symptoms. The study also illustrates dissociation in the time course of the two different dissociative symptoms in the same patient.

Facilitation by serum albumin of renal tubular secretion of organic anions.

The role of albumin in tubular secretion of the organic anions p-aminohippurate (PAH, 21% albumin-bound at 1 microM) and methotrexate (MTX, 55% bound at 1 microM), and of the organic cation N1-methylnicotinamide (NMN, not bound), was investigated in isolated rabbit S2 proximal tubules. PAH or MTX secretory rates were low in the absence of colloids or in the presence of 1 g/dl dextran 40, and were reversibly two- to sevenfold stimulated by either 1 g/dl bovine (BSA, either regular, defatted, and/or dialyzed) or rabbit serum albumin, or by dialyzed native rabbit plasma. NMN secretion was not stimulated by either dextran or albumin. Luminal BSA had no effect, but stimulation of PAH secretion was observed when albumin was present in both lumen and bath. This secretion was BSA concentration-dependent up to a 1 g/dl BSA. Saturation experiments suggested that 1 g/dl BSA may increase PAH apparent affinity for secretion, with no change in its maximum velocity. Albumin appears therefore to facilitate organic anion proximal secretion by an effect unrelated to oncotic pressure or to the extent of organic anion binding.

Randomized observation periods for the compound Poisson risk model: Dividends

In the framework of the classical compound Poisson process in collective risk theory, we study a modification of the horizontal dividend barrier strategy by introducing random observation times at which dividends can be paid and ruin can be observed. This model contains both the continuous-time and the discrete-time risk model as a limit and represents a certain type of bridge between them which still enables the explicit calculation of moments of total discounted dividend payments until ruin. Numerical illustrations for several sets of parameters are given and the effect of random observation times on the performance of the dividend strategy is studied.