A need for determination of arsenic species at low levels in cereal-based food and infant cereals. Validation of a method by LC-ICPMS.

The present study arose from the need to determine inorganic arsenic (iAs) at low levels in cereal-based food. Validated methods with a low limit of detection (LOD) are required to analyse these kinds of food. An analytical method for the determination of iAs, methylarsonic acid (MA) and dimethylarsinic acid (DMA) in cereal-based food and infant cereals is reported. The method was optimised and validated to achieve low LODs. Ion chromatography-inductively coupled plasma mass spectrometry (LC-ICPMS) was used for arsenic speciation. The main quality parameters were established. To expand the applicability of the method, different cereal products were analysed: bread, biscuits, breakfast cereals, wheat flour, corn snacks, pasta and infant cereals. The total and inorganic arsenic content of 29 cereal-based food samples ranged between 3.7-35.6 and 3.1-26.0 microg As kg-1, respectively. The present method could be considered a valuable tool for assessing inorganic arsenic contents in cereal-based foods.

Simultaneous determination of human plasma levels of citalopram, paroxetine, sertraline, and their metabolites by gas chromatography-mass spectrometry.

A gas chromatography-mass spectrometry method is presented which allows the simultaneous determination of the plasma concentrations of the selective serotonin reuptake inhibitors citalopram, paroxetine, sertraline, and their pharmacologically active N-demethylated metabolites (desmethylcitalopram, didesmethylcitalopram, and desmethylsertraline) after derivatization with the reagent N-methyl-bis(trifluoroacetamide). No interferences from endogenous compounds are observed following the extraction of plasma samples from six different human subjects. The standard curves are linear over a working range of 10-500 ng/mL for citalopram, 10-300 ng/mL for desmethylcitalopram, 5-60 ng/mL for didesmethylcitalopram, 20-400 ng/mL for sertraline and desmethylsertraline, and 10-200 ng/mL for paroxetine. Recoveries measured at three concentrations range from 81 to 118% for the tertiary amines (citalopram and the internal standard methylmaprotiline), 73 to 95% for the secondary amines (desmethylcitalopram, paroxetine and sertraline), and 39 to 66% for the primary amines (didesmethylcitalopram and desmethylsertraline). Intra- and interday coefficients of variation determined at three concentrations range from 3 to 11% for citalopram and its metabolites, 4 to 15% for paroxetine, and 5 to 13% for sertraline and desmethylsertraline. The limits of quantitation of the method are 2 ng/mL for citalopram and paroxetine, 1 ng/mL for sertraline, and 0.5 ng/mL for desmethylcitalopram, didesmethylcitalopram, and desmethylsertraline. No interferences are noted from 20 other psychotropic drugs. This sensitive and specific method can be used for single-dose pharmacokinetics. It is also useful for therapeutic drug monitoring of these three drugs and could possibly be adapted for the quantitation of the two other selective serotonin reuptake inhibitors on the market, namely fluoxetine and fluvoxamine.

Transient suppression of Shigella flexneri type 3 secretion by a protective O-antigen-specific monoclonal IgA.

Mucosal immunity to the enteric pathogen Shigella flexneri is mediated by secretory IgA (S-IgA) antibodies directed against the O-antigen (O-Ag) side chain of lipopolysaccharide. While secretory antibodies against the O-Ag are known to prevent bacterial invasion of the intestinal epithelium, the mechanisms by which this occurs are not fully understood. In this study, we report that the binding of a murine monoclonal IgA (IgAC5) to the O-Ag of S. flexneri serotype 5a suppresses activity of the type 3 secretion (T3S) system, which is necessary for S. flexneri to gain entry into intestinal epithelial cells. IgAC5's effects on the T3S were rapid (5 to 15 min) and were coincident with a partial reduction in the bacterial membrane potential and a decrease in intracellular ATP levels. Activity of the T3S system returned to normal levels 45 to 90 min following antibody treatment, demonstrating that IgAC5's effects were transient. Nonetheless, these data suggest a model in which the association of IgA with the O-Ag of S. flexneri partially de-energizes the T3S system and temporarily renders the bacterium incapable of invading intestinal epithelial cells. IMPORTANCE: Secretory IgA (S-IgA) serves as the first line of defense against enteric infections. However, despite its well-recognized role in mucosal immunity, relatively little is known at the molecular level about how this class of antibody functions to prevent pathogenic bacteria from penetrating the epithelial barrier. It is generally assumed that S-IgA functions primarily by "immune exclusion," a phenomenon in which the antibody binds to microbial surface antigens and thereby promotes bacterial agglutination, entrapment in mucus, and physical clearance from the gastrointestinal tract via peristalsis. The results of the present study suggest that in addition to serving as a physical barrier, S-IgA may have a direct impact on the ability of microbial pathogens to secrete virulence factors required for invasion of intestinal epithelial cells.

Grazing intensities and poultry litter fertilization levels on corn and black oat yield

The objective of this work was to assess the effect of poultry litter fertilization levels on corn and black oat yield using different grazing intensities, poultry litter levels (mixture of manure and bedding material) and a chemical fertilization level. The experimental design was a randomized complete block in a split-plot arrangement with four replicates. Black oat + ryegrass grazing intensities, characterized by different pasture sward management, with animal entrance at 25, 30 and 35-cm heights and exit at 5.0, 10 and 15-cm heights, were established at the main plots. After the grazing period, corn was grown at the subplots with four levels of poultry litter (0, 4,953, 9,907 and 14,860 kg ha-1), aiming to supply 0, 100, 200 and 300 kg ha-1 of nitrogen, and a treatment with chemical fertilizer, according to soil analysis. Grazing intensities had no effect on corn yield. Corn yield was 7,493, 8,458, 9,188, 10,247 and 11,028 kg ha-1, respectively, for the treatments without and with 4,953, 9,907 and 14,860 kg ha-1 of poultry litter, and the treatment with chemical fertilization. Poultry litter levels have a residual effect on the production of black oat grown in succession to corn.

Transpiration response of upland rice to water deficit changed by different levels of eucalyptus biochar

The objective of this work was to evaluate the effect of eucalyptus biochar on the transpiration rate of upland rice 'BRSMG Curinga' as an alternative means to decrease the effect of water stress on plant growth and development. Two-pot experiments were carried out using a completely randomized block design, in a split-plot arrangement, with six replicates. Main plots were water stress (WS) and no-water stress (NWS), and the subplots were biochar doses at 0, 6, 12 and 24% in growing medium (sand). Total transpirable soil water (TTSW), the p factor - defined as the average fraction of TTSW which can be depleted from the root zone before water stress limits growth -, and the normalized transpiration rate (NTR) were determined. Biochar addition increased TTSW and the p factor, and reduced NTR. Consequently, biochar addition was able to change the moisture threshold (p factor) of the growing medium, up to 12% maximum concentration, delaying the point where transpiration declines and affects yield.

Performance of juveniles of Pseudoplatystoma fasciatum fed graded levels of corn gluten meal

The objective of this work was to evaluate corn gluten meal (CGM) as a substitute for fish meal in diets for striped catfish (Pseudoplatystoma fasciatum) juveniles. Eight isonitrogenous (46% crude protein) and isoenergetic (3,450 kcal kg-1 digestible energy) diets, with increasing levels of CGM - 0, 6, 12, 18, 24, 30, 36, and 42% -, were fed to juvenile striped catfish (113.56±5.10 g) for seven weeks. Maximum values for weight gain, specific growth rate, protein efficiency ratio and feed conversion ratio, evaluated by polynomial quadratic regression, were observed with 10.4, 11.4, 15.4 and 15% of CGM inclusion, respectively. Feed intake decreased significantly from 0.8% CGM. Mesenteric fat index and body gross energy decreased linearly with increasing levels of CGM; minimum body protein contents were observed with 34.1% CGM. Yellow pigmentation of fillets significantly increased until 26.5% CGM, and decreased from this point forth. Both plasma glucose and protein concentrations decreased with increased CGM levels. The inclusion of 10-15% CGM promotes optimum of striped catfish juveniles depending on the parameter evaluated. Yellow coloration in fillets produced by CGM diets can have marketing implications.

Patient doses in CT examinations in Switzerland: implementation of national diagnostic reference levels.

Diagnostic reference levels (DRLs) were established for 21 indication-based CT examinations for adults in Switzerland. One hundred and seventy-nine of 225 computed tomography (CT) scanners operated in hospitals and private radiology institutes were audited on-site and patient doses were collected. For each CT scanner, a correction factor was calculated expressing the deviation of the measured weighted computed tomography dose index (CTDI) to the nominal weighted CTDI as displayed on the workstation. Patient doses were corrected by this factor providing a realistic basis for establishing national DRLs. Results showed large variations in doses between different radiology departments in Switzerland, especially for examinations of the petrous bone, pelvis, lower limbs and heart. This indicates that the concept of DRLs has not yet been correctly applied for CT examinations in clinical routine. A close collaboration of all stakeholders is mandatory to assure an effective radiation protection of patients. On-site audits will be intensified to further establish the concept of DRLs in Switzerland.

Recognition of Gram-positive Intestinal Bacteria by Hybridoma- and Colostrum-derived Secretory Immunoglobulin A Is Mediated by Carbohydrates.

Humans live in symbiosis with 10(14) commensal bacteria among which >99% resides in their gastrointestinal tract. The molecular bases pertaining to the interaction between mucosal secretory IgA (SIgA) and bacteria residing in the intestine are not known. Previous studies have demonstrated that commensals are naturally coated by SIgA in the gut lumen. Thus, understanding how natural SIgA interacts with commensal bacteria can provide new clues on its multiple functions at mucosal surfaces. Using fluorescently labeled, nonspecific SIgA or secretory component (SC), we visualized by confocal microscopy the interaction with various commensal bacteria, including Lactobacillus, Bifidobacteria, Escherichia coli, and Bacteroides strains. These experiments revealed that the interaction between SIgA and commensal bacteria involves Fab- and Fc-independent structural motifs, featuring SC as a crucial partner. Removal of glycans present on free SC or bound in SIgA resulted in a drastic drop in the interaction with Gram-positive bacteria, indicating the essential role of carbohydrates in the process. In contrast, poor binding of Gram-positive bacteria by control IgG was observed. The interaction with Gram-negative bacteria was preserved whatever the molecular form of protein partner used, suggesting the involvement of different binding motifs. Purified SIgA and SC from either mouse hybridoma cells or human colostrum exhibited identical patterns of recognition for Gram-positive bacteria, emphasizing conserved plasticity between species. Thus, sugar-mediated binding of commensals by SIgA highlights the currently underappreciated role of glycans in mediating the interaction between a highly diverse microbiota and the mucosal immune system.

Impact of enhanced compliance initiatives on the efficacy of rosuvastatin in reducing low density lipoprotein cholesterol levels in patients with primary hypercholesterolaemia.

The effectiveness of lipid-lowering medication critically depends on the patients' compliance and the efficacy of the prescribed drug. The primary objective of this multicentre study was to compare the efficacy of rosuvastatin with or without access to compliance initiatives, in bringing patients to the Joint European Task Force's (1998) recommended low-density lipoprotein cholesterol (LDL-C) level goal (LDL-C, <3.0 mmol/L) at week 24. Secondary objectives were comparison of the number and percentage of patients achieving European goals (1998, 2003) for LDL-C and other lipid parameters. Patients with primary hypercholesterolaemia and a 10-year coronary heart disease risk of >20% received open label rosuvastatin treatment for 24 weeks with or without access to compliance enhancement tools. The initial daily dosage of 10 mg could be doubled at week 12. Compliance tools included: a) a starter pack for subjects containing a videotape, an educational leaflet, a passport/goal diary and details of the helpline and/or website; b) regular personalised letters to provide message reinforcement; c) a toll-free helpline and a website. The majority of patients (67%) achieved the 1998 European goal for LDL-C at week 24. 31% required an increase in dosage of rosuvastatin to 20 mg at week 12. Compliance enhancement tools did not increase the number of patients achieving either the 1998 or the 2003 European target for plasma lipids. Rosuvastatin was well tolerated during this study. The safety profile was comparable with other drugs of the same class. 63 patients in the 10 mg group and 58 in the 10 mg Plus group discontinued treatment. The main reasons for discontinuation were adverse events (39 patients in the 10 mg group; 35 patients in the 10 mg Plus group) and loss to follow-up (13 patients in the 10 mg group; 9 patients in the 10 mg Plus group). The two most frequently reported adverse events were myalgia (34 patients, 3% respectively) and back pain (23 patients, 2% respectively). The overall rate of temporary or permanent study discontinuation due to adverse events was 9% (n = 101) in patients receiving 10 mg rosuvastatin and 3% (n = 9) in patients titrated up to 20 mg rosuvastatin. Rosuvastatin was effective in lowering LDL-C values in patients with hypercholesterolaemia to the 1998 European target at week 24. However, compliance enhancement tools did not increase the number of patients achieving any European targets for plasma lipids.

Growth and hematology of pacu subjected to sustained swimming and fed different protein levels

The objective of this work was to evaluate the effect of sustained swimming and dietary protein levels on growth and hematological responses of juvenile pacu (Piaractus mesopotamicus). A completely randomized design was used in a 3x2 factorial arrangement, with three levels of dietary protein (24, 28, and 32% crude protein), two rearing conditions (sustained swimming or motionless water), and 15 replicates. Fish were subjected to sustained swimming at the velocity of two body lengths per second (2 BL s-1), for 45 days. The level of dietary protein and the swimming conditions affected the performance, growth, and hematological profile of pacu. Swimming conditions influenced nutritional factors, increasing daily weight gain, specific growth rate, number of erythrocytes, mean corpuscular volume, and mean corpuscular hemoglobin. Fish under sustained swimming and fed with 24% crude protein showed better growth performance, with higher specific growth rate (4.11±0.88) and higher daily weight gain (2.19±0.47 g per day). Sustained swimming can increase the productive performance of pacu and simultaneously reduce dietary protein levels.

The effect of 4-chlororesorcinol on the endogenous levels of IAA, ABA and oxidative enzymes in cuttings

Treatment of bean cuttings with 4-chlororesorcinol (4-CR), known to increase the number of roots and extend their distribution, prevented the accumulation of free indol-3-yl-acetic acid (IAA) in the hypocotyls within 24 h after cutting preparation. In mung bean there was no change in the distribution (upper half vs. 1 ower half of the hypocotyl) of IAA within the hypocotyl as a result of the treatment. In bean cuttings the treatment with 4-CR prevented the accumulation of IAA in the bottom of the cutting. Oxidation of IAA as a measure of IAA oxidase activity in bean was enhanced appreciably by 4-chlororesorcinol. The level of abscisic acid in mung bean, on the other hand, remained 3-4 fold higher than in the control, yet still about 50% lower than the zero time level. In untreated mung bean cuttings the activity of peroxidase increased after cutting preparation. In contrast, the activity of peroxidase in 4-Cr-treated cuttings was consistently lower. In order to relate to the effect of exogenously applied auxin the level of peroxidase was measured also in indol-3-yl-butyric acid-treated cuttings. The overall peroxidase activity in IBA-treated cuttings was not affected. However, when assaying for the different isozymes the drop in peroxidase activity was most evident in the inducible basic isoperoxidases both in 4-CR and IBA treatments. It appears that the exposure to 4-CR exerts an effect that is similar to that of exogenously applied auxin, affecting the activity of basic peroxidases and enhancing the oxidation of endogenous IAA, thus allowing the organization of the primordia.

Plasma levels of luteinizing hormone and gonadal maturation of lambari females under different photoperiods

The objective of this work was to evaluate the effect of photoperiod on luteinizing hormone (LH) plasma levels and gonadal maturation of lambari females. One hundred and twenty adult lambaris, distributed into 12 aquaria of 20 L each, were randomly subjected to three different treatments, in a completely randomized design, and four replicates. Treatments were photoperiods in hours of light (L) and darkness (D): T1, 0 L:24 D; T2, 12 L:12 D; T3, 24 L:0 D. After 40 days, fish were subjected to fasting for 24 hours and, then, anesthetized. Immediately after slaughter, fish were weighed, and their gonads and livers were removed and weighed. Ovaries were weighed and immersed in Bouin's fixative solution for 24 hours and, then, kept in 70% alcohol until processing the material. Subsequently, the oocyte developmental stage was determined. No significant differences were observed between treatments for final weight, ovary weight, gonadosomatic index (GSI), hepatosomatic index (HSI) and LH levels. In all treatments, lambari females showed maturing ovaries with prevalence of vitellogenic oocytes. Photoperiod does not affect the LH levels and ovarian maturation in lambari females.

Intravenous immunoglobulin for treatment of mild-to-moderate Alzheimer's disease: a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial.

BACKGROUND: Three small trials suggest that intravenous immunoglobulin can affect biomarkers and symptoms of mild-to-moderate Alzheimer's disease. We tested the safety, effective dose, and infusion interval of intravenous immunoglobulin in such patients. METHODS: We did a multicentre, placebo-controlled phase 2 trial at seven sites in the USA and five in Germany. Participants with probable Alzheimer's disease aged 50-85 years were randomly assigned (by a computer-generated randomisation sequence, with block sizes of eight) to infusions every 4 weeks (0·2, 0·5, or 0·8 g intravenous immunoglobulin per kg bodyweight, or placebo) or infusions every 2 weeks (0·1, 0·25, or 0·4 g/kg, or placebo). Patients, caregivers, investigators assessing outcomes, and staff at imaging facilities and the clinical research organisation were masked to treatment allocation, but dispensing pharmacists, the statistician, and the person responsible for final PET analyses were not. Treatment was masked with opaque pouches and infusion lines. The primary endpoint was median area under the curve (AUC) of plasma amyloid β (Aβ)(1-40) between the last infusion and the final visit (2 weeks or 4 weeks depending on infusion interval) in the intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT00812565) and controlled-trials.com (ISRCTN64846759). FINDINGS: 89 patients were assessed for eligibility, of whom 58 were enrolled and 55 included in the primary analysis. Median AUC of plasma Aβ(1-40) was not significantly different for intravenous immunoglobulin compared with placebo for five of the six intervention groups (-18·0 [range -1347·0 to 1068·5] for 0·2 g/kg, -364·3 [-5834·5 to 1953·5] for 0·5 g/kg, and -351·8 [-1084·0 to 936·5] for 0·8 g/kg every 4 weeks vs -116·3 [-1379·0 to 5266·0] for placebo; and -13·8 [-1729·0 to 307·0] for 0·1 g/kg, and -32·5 [-1102·5 to 451·5] for 0·25 g/kg every 2 weeks vs 159·5 [51·5 to 303·0] for placebo; p>0·05 for all). The difference in median AUC of plasma Aβ(1-40) between the 0·4 g/kg every 2 weeks group (47·0 [range -341·0 to 72·5]) and the placebo group was significant (p=0·0216). 25 of 42 (60%) patients in the intervention group versus nine of 14 (64%) receiving placebo had an adverse event. Four of 42 (10%) patients in the intravenous immunoglobulin group versus four of 14 (29%) receiving placebo had a serious adverse event, including one stroke in the intervention group. INTERPRETATION: Intravenous immunoglobulin may have an acceptable safety profile. Our results did not accord with those from previous studies. Longer trials with greater power are needed to assess the cognitive and functional effects of intravenous immunoglobulin in patients with Alzheimer's disease.