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BACKGROUND: To evaluate the effect of fingolimod in visual function and neuroretinal structures in patients with multiple sclerosis (MS) for a period of 1 year. METHODS: This longitudinal and observational cohort study included 78 eyes of 78 patients with MS treated with fingolimod. All subjects were evaluated every 3 months during 12 months and compared with 32 patients treated with interferon beta. All patients were examined for high-contrast and low-contrast (2.5% and 1.25%) visual acuity (VA), contrast sensitivity vision (CSV) (using Pelli-Robson and CSV-1000E tests), color vision (Farnsworth D-15 and L''Anthony D-15 desaturated tests), and retinal structural measurements (retinal nerve fiber layer [RNFL] and ganglion cell layer [GCL] thickness) using optical coherence tomography (OCT) technology. RESULTS: Patients with MS treated with fingolimod for a period of 1 year showed significant reduction in 100% and 1.25% contrast VA (P = 0.009 and 0.008, respectively), an alteration of contrast sensitivity and color perception (Pelli-Robson test, CSV-1000E test, Farnsworth D-15 desaturated test, and L''Anthony D-15 desaturated test; P < 0.001), GCL thickness reduction (P = 0.007), and an average macular central thickness increase of 2.6 µm (P = 0.006). Patients with MS treated with interferon beta did not show significant changes in visual function tests neither in macular thickness measurements, but they showed a significant reduction in GCL and RNFL thicknesses. The reduction in neuroretinal structures observed by OCT was significantly higher in the interferon-beta group, but patients treated with fingolimod showed a significant increase in macular central thickness and a reduction in low contrast vision (P < 0.001). CONCLUSIONS: Patients with MS treated with fingolimod and with no clinically observable macular edema show a significant change in visual function parameters and average macular central thickness increase compared with those treated with interferon beta. These findings are probably due to subclinical macular edema produced by fingolimod, which might be considered as an indicator for pharmacovigilance of sphingosine-1-phosphate inhibitors to be improved. Copyright © 2020 by North American Neuro-Ophthalmology Society.

Analytical techniques are extensively used in various fields of human activity to define quality and usage safety patterns of goods and consumables. Between those, liquid chromatography is probably the most common, generally combined with optical detectors. Alternatively, electroanalytical techniques provide versatile tools that offer high selectivity and sensitivity in a short time, using simple and low cost instrumentation. Amperometric, coulometric and conductimetric detectors are thus well established in HPLC with commercially available instrumentation. Despite sharing some of the stated features, the use of potentiometric detectors seems however overlooked. Potentiometry with ion-selective electrodes has been highlighted in both batch and flow analysis systems, evidenced by numerous applications performed worldwide. The determination of electrolytes in blood samples, heavy metals in natural water samples and pharmaceutical drugs in bulk drug materials are some of the representative examples. The developments achieved so far in hydrodynamic separation systems proved the great potential of potentiometry to become a competitive detection technique with the many others. Therefore, it is intended to present an overview about potentiometric detection in liquid chromatography with the purpose of enhance its importance for future analytical applications.

Glioblastoma multiforme (GBM) is the most aggressive human brain tumor, and GBM stem cells (GSC) may be responsible for its recurrence and therapeutic resistance. Toll-like receptors (TLRs), which recognize multiple ligands (endogenous and pathogen-associated) and trigger the immune response of mature immune cells, are also expressed by hematopoietic stem and progenitor cells, where their activation results in the differentiation of these cells into myeloid cells. Since TLR expression has been recently described in neural cells, including neural stem cells, we studied TLR expression by GSCs and the effect of stimulation by TLR ligands on promoting GSC differentiation into mature GBM cells. First, our results showed heterogeneous TLR expression by GBM cells from human tumors and, for the first time, by human GSCs defined by their CD133+ and CD44+ phenotypes. Next, the effect of TLR ligands was studied in in vitro cell cultures of neurospheres and CD44+ cells obtained from two GBM cell lines (U-87 and U-118). The expression of GSC markers diminished in the presence of Pam3CSK4 or LPS (TLR2 and TLR4 ligands, respectively), thus indicating TLR-dependent differentiation. Interestingly, simultaneous treatment with Pam3CSK4 plus temozolomide (TMZ), the reference drug in GBM treatment, significantly increased cell death compared to the effect of the ligand alone, which showed no toxicity, or TMZ alone. These results suggest a synergistic effect between Pam3CSK4 and TMZ based on the induction of TLR-dependent GSC differentiation towards mature GBM cells, which exhibited increased sensitivity to chemotherapy, and provide new perspectives in GBM therapy.

Determination of ten biogenic amines in alcoholic beverages by HPLC coupled to a potentiometric detector for food quality control is herein presented. Biogenic amines were separated by ion-pair chromatography on a C18 column using a gradient mobile phase of acetic acid, acetonitrile, and butane-sulfonic acid. Detection was accomplished by a miniaturized amine-selective electrode. The method was validated following ICH and Eurachem guidelines. Linear regression models provided R2 values from 0.9870 ± 0.0019 to 0.9991 ± 0.0014 for tyramine and cadaverine, respectively. Detection and quantification limits depend on the molecular weight of BAs, ranging from 9.3 to 60.5 and from 31.1 to 202.3 µg L−1 for methylamine and spermine, respectively. Repeatability and intermediate precision showed RSD values lower than 5.8 and 8.3%, respectively. Accuracy of assays yielded recovery values from 86.4 to 109.9%. The biogenic amines content in red wine, white wine, and beer samples were 7.54, 5.24, and 4.58 mg L-1, respectively.

Glioblastoma (GBM) is the most frequent and aggressive primary brain tumor and is associated with a poor prognosis. Despite the use of combined treatment approaches, recurrence is almost inevitable and survival longer than 14 or 15 months after diagnosis is low. It is therefore necessary to identify new therapeutic targets to fight GBM progression and recurrence. Some publications have pointed out the role of glioma stem cells (GSCs) as the origin of GBM. These cells, with characteristics of neural stem cells (NSC) present in physiological neurogenic niches, have been proposed as being responsible for the high resistance of GBM to current treatments such as temozolomide (TMZ). The protein Kinase C (PKC) family members play an essential role in transducing signals related with cell cycle entrance, differentiation and apoptosis in NSC and participate in distinct signaling cascades that determine NSC and GSC dynamics. Thus, PKC could be a suitable druggable target to treat recurrent GBM. Clinical trials have tested the efficacy of PKCβ inhibitors, and preclinical studies have focused on other PKC isozymes. Here, we discuss the idea that other PKC isozymes may also be involved in GBM progression and that the development of a new generation of effective drugs should consider the balance between the activation of different PKC subtypes. Integrated Territorial Investment Operational Programme of the European Commission and by the Department of Department of Health and Families (Consejería de Salud y Familias) of the Regional Government of Andalusia. Project reference: ITI0042-2019: ITI Cadiz 2019

Este artículo se encuentra disponible en la siguiente URL: https://www.mdpi.com/1422-0067/22/3/1375 Este artículo pertenece al número especial "The Role of Mesenchymal Stem Cells on Inflammatory and Fibrotic Diseases". Adipose tissue represents an abundant source of mesenchymal stem cells (MSC) for therapeutic purposes. Previous studies have demonstrated the anti-inflammatory potential of adipose tissue-derived MSC (ASC). Extracellular vesicles (EV) present in the conditioned medium (CM) have been shown to mediate the cytoprotective effects of human ASC secretome. Nevertheless, the role of EV in the anti-inflammatory effects of mouse-derived ASC is not known. The current study has investigated the influence of mouse-derived ASC CM and its fractions on the response of mouse-derived peritoneal macrophages against lipopolysaccharide (LPS). CM and its soluble fraction reduced the release of pro-inflammatory cytokines, adenosine triphosphate and nitric oxide in stimulated cells. They also enhanced the migration of neutrophils or monocytes, in the absence or presence of LPS, respectively, which is likely related to the presence of chemokines, and reduced the phagocytic response. The anti-inflammatory effect of CM may be dependent on the regulation of toll-like receptor 4 expression and nuclear factor- B activation. Our results demonstrate the antiinflammatory effects of mouse-derived ASC secretome in mouse-derived peritoneal macrophages stimulated with LPS and show that they are not mediated by EV.

Aims Although intrauterine growth restriction (IUGR) impairs immune system homeostasis and lung development, its relationship with the susceptibility to pulmonary infections remains unclear. Thus, this study aimed to investigate the impact of IUGR on acute lung inflammatory response induced by bacterial stimulus. Materials and methods Pregnant female Wistar rats were subjected to 50% caloric-protein food restriction during gestation. To mimic bacterial lung infection, adult male offspring (12 weeks old) were challenged with a single lipopolysaccharide (LPS) intranasal instillation, and 6 h later, we assessed the acute inflammatory response. Normal birth weight (NBW) animals represent the control group. Key findings LPS instillation increased the protein levels in the airways of both the NBW and low birth weight (LBW) groups, indicating vascular leakage. LBW animals exhibited a lower number of neutrophils, reduced production of interleukin-6 and macrophage-inflammatory protein-2 and decreased upregulation of intercellular adhesion molecule-1 gene expression in lung tissues. Further analysis revealed that the LBW group produced lower levels of prostaglandin-E2 and failed to secrete leukotriene-B4 upon LPS stimulation, which correlated with impaired cyclooxygenase-2 and 5-lipoxygenase expression. These results were probably associated with their inability to upregulate the expression of Toll-like receptor-4 and downstream signaling proteins, such as nuclear factor kappa-B, in the lungs. The LBW group also exhibited abnormal airway thickening and high corticosterone levels under basal conditions. Significance This study suggests that IUGR-induced foetal programming in LBW offspring threatens HPA axis physiology and corticosterone biodisponibility, and impairs the innate response to bacterial antigens, increasing future susceptibility to pulmonary infection.

Different cellular mechanisms have been described as being potentially involved in the progression of neurodegeneration in Parkinson’s disease, although their role is still unclear. The present study aimed to identify in detail, through differentially expressed genes analysis by bioinformatics approaches, the molecular mechanisms triggered after a systemic insult in parkinsonian mice. To address this objective, we combined a dextran sodium sulfate (DSS)-induced ulcerative colitis experimental mice model with an acute 1-methyl-4-phenyl-1,2,3,6-tetradropyridine (MPTP) intoxication. The animals were divided into four experimental groups based on the different treatments: (i) control, (ii) DSS, (iii) MPTP and (iv) MPTP + DSS. The data obtained by microarray and functional enrichment analysis point out the implication of different molecular mechanisms depending on the experimental condition. We see, in the striatum of animals intoxicated only with DSS, dysfunction processes related to the blood. On the other hand, oxidative stress processes are more prominent at the MPTP intoxicated mice. Finally, differentially expressed genes within the MPTP + DSS show functional enrichment in inflammation and programmed cell death. Interestingly, we identify a significant synergistic negative effect of both toxins since the expression of differentially expressed genes (DEGs) related to balanced cellular homeostasis was not enough to prevent processes associated with cell death. This work provides detailed insights into the involvement of systemic inflammation, triggered after an insult in the colon, in the progression of the degeneration in Parkinsonism. In this way, we will be able to identify promising therapeutic targets that prevent the contribution of inflammatory processes in the progression of Parkinson’s disease.

The thermal helium beam diagnostic at ASDEX Upgrade can access the whole plasma edge region simultaneously with a high spatiotemporal resolution. Manifold dynamics of plasma edge transport is observed for different plasma confinement regimes, comprising L- and H-mode scenarios with type-I and small ELMs as well as ELM free EDA regimes. The measurements show that the plasma dynamics in the confined region close to the separatrix is often dominated by regular high frequency modes (10–100 kHz), whereas filaments with an intermittent occurrence rate of 0.1–2 kHz dominate in particular the far scrape-off layer (SOL). The comparison among different regimes shows a similar filamentary activity between L-mode and inter-ELM H-mode phases. An increased filamentary activity in H-mode, however, is found for rising densities n ∕ n GW . This is the case for the regime of quasi continuous exhaust (QCE) with three times higher filament velocities compared to a clean inter-ELM H-mode.

The inferior colliculus (IC) is an important midbrain relay station for the integration of descending and ascending auditory information. Additionally, the IC has been implicated in processing sensorimotor responses. Glutamatergic and GABAergic manipulations in the IC can improve motor deficits as demonstrated by the animal model of haloperidol-induced catalepsy. However, how the IC influences motor function remains unclear. We investigated the effects of either intracollicular deep brain stimulation (DBS) or microinjection of the glutamatergic antagonist MK-801 or the agonist NMDA in C57BL/6J mice chronically treated with saline or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). After DBS or microinjections, the mice were submitted to rotarod and open field tests, respectively. DBS in the IC was effective to increase the time spent on the rotarod in MPTP-treated mice. After unilateral microinjection of MK-801, but not NMDA, MPTP-treated mice increased the distance travelled in the open field (p 0.05). In conclusion, intracollicular DBS or MK-801 microinjection can improve motor performance in parkinsonian mice suggesting the IC as a new and non-conventional therapeutic target in motor impairment.

[EN] Tendon and ligament shows extremely limited endogenous regenerative capacity. Current treatments are based on the replacement and or augmentation of the injured tissue but the repaired tissue rarely achieve functionality equal to that of the preinjured tissue. To address this challenge, tissue engineering has emerged as a promising strategy. This study develops a regenerative and resorbable hybrid construct for tendon and ligament engineering. The construct is made up by a hollow poly-lactic acid braid with embedded microspheres carrying cells and an anti-adherent coating, with all the parts being made of biodegradable materials. This assembly intends to regenerate the tissue starting from the interior of the construct towards outside while it degrades. Fibroblasts cultured on poly lactic acid and hyaluronic acid microspheres for 6 h were injected into the hollow braid and the construct was cultured for 14 days. The cells thus transported into the lumen of the construct were able to migrate and adhere to the braid fibers naturally, leading to a homogeneous proliferation inside the braid. Moreover, no cells were found on the outer surface of the coating. Altogether, this study demonstrated that PLA/HA hybrid construct could be a promising material for tendon and ligament repair., This work was supported by AITEX (Textil Research Institute, Alcoi, Alicante, Spain) through the researching contract "Development of braided biomaterials for biomedical applications'' and also funded by AEI "RTI2018-095872-B-C21 and C22/ERDF''.

To evaluate neurodegeneration in patients with type 2 Diabetes Mellitus (DM2) without diabetic retinopathy, and to assess the possible role of chronic systemic ischaemia and disease duration in retinal changes. Observational cross sectional study. Sixty eyes of 60 patients with DM2 without signs of diabetic retinopathy (DR), and 60 eyes of 60 healthy controls underwent retinal (ganglion cell layer (GCL), and retinal nerve fiber layer (RNFL) and choroidal evaluation using Swept source Optical coherence tomography, which allows high quality analysis of the different retinal layers and the choroidal plexus. Comparison between patients with presence/absence of systemic vascular complications and different disease duration time was performed. Macular GCL and RNFL were reduced in patients compared to controls (p

Purpose. To evaluate neurodegeneration in patients with type 2 diabetes mellitus (DM2) without diabetic retinopathy and to assess the possible role of systemic vascular complications in retinal changes. Methods. Sixty eyes of 60 patients with DM2 and without any signs of diabetic retinopathy and 60 eyes of 60 healthy controls underwent retinal evaluation using Spectralis optical coherence tomography. Macular ganglion cell layer (GCL) and retinal nerve fiber layer (RNFL) were evaluated. Peripapillary RNFL thickness was assessed using Glaucoma and Axonal Analytics applications. Comparison between patients with the presence/absence of systemic vascular complications and different disease duration was made. Results. Macular GCL was reduced in patients compared to controls (p<0.001). Differences in the macular RNFL thickness were only observed in the outer inferior sector (p=0.033). A reduction in the peripapillary RNFL (average, inferior, and inferotemporal thickness, p<0.05 for all three) was observed in patients using both applications. Patients with chronic systemic vascular complications presented a reduction in the temporal RNFL (p=0.019) compared to patients without complications. The superotemporal RNFL thickness was thinner in patients with longer disease duration. Conclusions. Patients with type 2 DM without diabetic retinopathy and good metabolic control present neurodegeneration affecting neurons in the macular area and axons in different sectors of the optic disc. Systemic vascular complications contributed to further axonal damage in these patients, suggesting a possible role of subclinical ischaemia to retinal neurodegeneration in type 2 DM.

It is described the determination of underivatized biogenic amines by ion-pair chromatography coupled to potentiometric detection, for food quality control. A wall-jet flow-cell was used to hold an amine-selective electrode, based on cucurbit[6]uril as an ionophore, and a commercial reference electrode. The biogenic amines were separated in less than 20 min using a C18 column as the stationary phase. This method comprises a gradient elution with a mobile phase containing lithium formate buffer, acetonitrile, and butane-sulfonic acid sodium salt as an ion-pair agent. The proposed method was validated following the International Council for harmonization guidelines. Calibration data fitted a linear regression model with R2 varying from 0.9804 to 0.9972. Repeatability intra and inter-day showed relative standard deviation values lower than 9.1% and 13.3%, respectively. Detection and quantification limits ranged from 0.03 to 0.20 mg L−1 and 0.09 to 0.61 mg L−1, respectively. Spiked tomato samples were analysed to assess the accuracy, yielding recovery values from 85.8 to 108.5%. The biogenic amines content in fresh tomatoes, canned chopped tomato, and pulp tomato was 7.11, 5.12, and 7.69 mg L−1, respectively.

Background Neuroprotective strategies are becoming relevant to slow down dopaminergic cell death and inflammatory processes related to the progressive neurodegeneration in Parkinson’s disease (PD). Interestingly, among others, physical activity (PA) or anti-oxidant agents (such as N-acetyl-L-cysteine, NAC) are common therapeutic strategies. Therefore, this study aims to analyze if there is a synergistic effect of physical activity along with NAC treatment on dopaminergic degeneration and neuroinflammatory response in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism model after subchronic intoxication. Methods To ascertain this possibility, 48 8-week-old male mice (C57BL/6 strain) were used. Twenty four of them were placed individually in cages where voluntary physical activity was automatically monitored during 30 days and were divided into groups: (i) control; (ii) NAC; (iii) MPTP, and (iv) MPTP+NAC. The other 24 mice were divided into the same four groups but without physical activity. Results The data collected during the treatment period showed that there was an overall increase in the total running distance in all groups under physical activity, including Parkinsonian animals. However, the monitoring data per day showed that the activity routine by MPTP and MPTP+NAC groups was disrupted by alterations in the circardian rhythm because of MPTP intoxication. Results from post-mortem studies in the substantia nigra pars compacta (SNpc) showed significant decrease in the number of TH+ cells in all MPTP groups. Moreover, TH+ expression in the striatum was significantly decreased in all MPTP groups. Thus, PA + NAC treatment do not protect dopaminergic neurons against a subchronic intoxication of MPTP. Regarding glial response, the results obtained from microglial analysis do not show significant increase in the number of Iba-1+ cell in MPTP+NAC and MPTP+PA + NAC. In the striatum, a significant decrease is observed only in the MPTP+NAC group compared with that of the MPTP group. The microglial results are reinforced by those obtained from the analysis of astroglial response, in which a decrease in the expression of GFAP+ cells are observed in MPTP+NAC and MPTP+PA + NAC compared with MPTP groups both in the SNpc and in the striatum. Finally, from the study of the astroglial response by the co-localization of GFAP/S100b, we described some expression patterns observed based on the severity of the damage produced by the MPTP intoxication in the different treated groups. Conclusions These results suggest that the combination of physical activity with an anti-oxidant agent does not have a synergistic neuroprotective effect in the nigrostriatal pathway. Our results show a potential positive effect, only due to NAC treatment, on the neuroinflammatory response after subchronic MPTP intoxication. Thus, physical activity is not essential, under these conditions. However, we believe that physical activity, used for therapeutic purposes, has a beneficial long-term effect. In this line, these results open the door to design longer studies to demonstrate its promising effect as neuroprotective strategy. Electronic supplementary material The online version of this article (10.1186/s12974-018-1357-4) contains supplementary material, which is available to authorized users.

BACKGROUND: The antibiotic lock therapy (ALT) technique that involves the instillation of a highly concentrated antimicrobial solution with additives such as anticoagulants into the catheter lumen, is an option for treatment of catheter-related bloodstream infections when the central venous catheter is retained. An important limitation is the frequent incompatibility between the components, causing great controversy in the literaure. The ALT with gentamicin is one of the most requested ALT for treating bacteriemias by Gram(-). The anticoagulant that is studied more is unfractioned heparin. It can be used in haemodialysis patients, however, other anticoagulants such as citrate whose data are limited regarding compatibility should be used for patients with a history of heparin-induced trombocytopenua (HIT) or active HIT. PURPOSE: To study the stability of the catheter lock solution that combines gentamicin 2.5 mg/ml and heparin 2500UI/mL or citrate 2% as anticoagulant. MATERIAL AND METHODS: Eight solutions of catheter lock were prepared at fixed concentrations: four solutions of gentamicin 2.5 mg/ml+heparin 2500UI/ml (A1, B1, C1, D1) and four of gentamicin 2.5 mg/ml+citrate 2% (A2, B2, C2, D2). Physical and chemical stability were measured on days 0 (A1, A2), 2 (B1, B2), 3 (C1, C2) and 7 (D1, D2) after the preparation. Two aliquots were prepared from solutions B1, B2 and C1, C2. One aliquot of each one (B1a, B2a, C1a, C2a) were stored in the refrigerator (2°C–8°C) to test the stability of the preparation of ALT extemporaneously prior to its use, and another (B1b, B2b, C1b, C2b) in the oven (35°C–37°C) to simulate the temperatures that are reached once installed in the catheter. Chemical stability was defined as concentrations of gentamicin at least 90% measured by the colourimetric technique. For the analysis the samples were diluted to a gentamycin concentration of 5 mcg/ml. Physical stability was considered as the absence of precipitate or appearance of particles. RESULTS: None of the ALT precipitated during the study nor did they showed variations in colour. The concentrations of gentamicin were stable in the different selected storage conditions: A1:5.31 mcg/mL; A2:5.46 mcg/mL; B1a:5.88 mcg/mL; B1b:5.8 mcg/mL; B2a:5.1 mcg/mL; B2b:4.97 mcg/mL; C1a:5.9 mcg/mL; C1b:5.47 mcg/mL; C2a:5.08 mcg/mL; C2b:5.21 mcg/mL; D1:5.46 mcg/mL; and D2:5.04 mcg/mL. The mean was 5.39±0,32 mcg/mL. CONCLUSION: The ALT with gentamicin 2.5 mg/ml and heparin 2500UI/ml or citrate 2% are chemically and physically stable. More studies are needed to address areas of uncertainty of great clinical relevance, such as the stability of ALT with other concentrations of gentamicin and ALT that combines other antibiotic with citrate. No conflict of interest

Background/Aims. We have previously shown that low birth weight (LBW) rats exposed to intrauterine malnutrition have an impaired lung inflammatory response and reduced levels of inflammatory mediators; however, circulating leptin levels were not increased. We evaluated long leptin receptor isoform (ObRb) expression in lung endothelial cells from low birth weight rats and examined its role in the production of lipid mediators and cytokines. Methods. Lung endothelial cells were obtained from normal birth weight (NBW) rats or LBW rats subjected to intrauterine malnutrition. These cells were stimulated with leptin (10 ng/mL), LPS (lipopolysaccharide, 1 μg/mL), or leptin plus LPS. Six hours after stimulation, the production of inflammatory mediators (PGE2, LTB4, IL-1β, and IL-6) was evaluated using commercial ELISA kits, and Western blotting was performed to investigate p38MAPK, NF-κB, and ObRb expression. Results. Leptin increased IL-1β levels in only cells from the NBW group, whereas LPS increased PGE2 and LTB4 levels in cells from both groups; leptin addition potentiated lipid mediator production induced by LPS in the NBW group. LPS enhanced the production of IL-1β and IL-6 in only endothelial cells from NBW rats. Leptin receptor expression was decreased (63%) in endothelial cells from LBW rats. None of the stimuli increased NF-κB or p38 signaling pathway expression in cells from LBW rats. Conclusion. These results suggest that intrauterine malnutrition compromises leptin receptor expression and cytokine production in pulmonary endothelial cells stimulated by LPS; these effects seem to involve the NF-κB and p38MAPK signaling pathways.

Highly aggressive cancer types such as pancreatic cancer possess a mortality rate of up to 80% within the first 6months after diagnosis. To reduce this high mortality rate, more sensitive diagnostic tools allowing an early stage medical imaging of even very small tumours are needed. For this purpose, magnetic, biodegradable nanoparticles prepared using recombinant human serum albumin (rHSA) and incorporated iron oxide (maghemite, γ-Fe2O3) nanoparticles were developed. Galectin-1 has been chosen as target receptor as this protein is upregulated in pancreatic cancer and its precursor lesions but not in healthy pancreatic tissue nor in pancreatitis. Tissue plasminogen activator derived peptides (t-PA-ligands), that have a high affinity to galectin-1 have been chosen as target moieties and were covalently attached onto the nanoparticle surface. Improved targeting and imaging properties were shown in mice using single photon emission computed tomography-computer tomography (SPECT-CT), a handheld gamma camera, and magnetic resonance imaging (MRI).

In this work, the new polyamine bisnaphthalimidopropyl-4,4’-diaminodiphenylmethane is proposed as a new ionophore for perchlorate potentiometric sensors. The optimal formulation for the membrane comprised of 12 mmol kg−1 of the ionophore, and 68 % (w/w) of 2-nitrophenyl phenyl ether as plasticizer and 31 % (w/w) of high molecular weight PVC. The sensors were soaked in water for a week to allow leakage of anionic impurities and for one day in a perchlorate solution (10−4 mol L−1) to improve reproducibility due to its first usage. The stability constant for the ionophore-perchlorate association in the membrane, log βIL1=3.18±0.04, ensured a performance characterized by the slope of 54.1 (±0.7) mV dec−1 to perchlorate solutions with concentrations between 1.24×10−7 and 1.00×10−3 mol L−1. The sensors are insensitive to pH between 3.5 to 11.0, they have a practical detection limit of 7.66 (±0.42) ×10−8 mol L−1 and a response time below 60 s for solutions with perchlorate concentrations above 5×10−6 mol L−1. The accuracy of the results was confirmed by the analysis of the contaminant in a certified reference water sample.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a well-known neuropeptide with strong neurotrophic and neuroprotective effects. PACAP exerts its protective actions via three G protein-coupled receptors: the specific Pac1 receptor (Pac1R) and the Vpac1/Vpac2 receptors, the neuroprotective effects being mainly mediated by the Pac1R. The protective role of PACAP in models of Parkinson's disease and other neurodegenerative diseases is now well-established in both in vitro and in vivo studies. PACAP and its receptors occur in the mammalian brain, including regions associated with Parkinson's disease. PACAP receptor upregulation or downregulation has been reported in several injury models or human diseases, but no data are available on alterations of receptor expression in Parkinson's disease. The model closest to the human disease is the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced macaque model. Therefore, our present aim was to evaluate changes in Pac1R expression in basal ganglia related to Parkinson's disease in a macaque model. Monkeys were rendered parkinsonian with MPTP, and striatum, pallidum, and cortex were evaluated for Pac1R immunostaining. We found that Pac1R immunosignal was markedly reduced in the caudate nucleus, putamen, and internal and external parts of the globus pallidus, while the immunoreactivity remained unchanged in the cortex of MPTP-treated parkinsonian monkey brains. This decrease was attenuated in some brain areas in monkeys treated with L-DOPA. The strong, specific decrease of the PACAP receptor immunosignal in the basal ganglia of parkinsonian macaque monkey brains suggests that the PACAP/Pac1R system may play an important role in the development/progression of the disease.

The present study examines the effect of the organic loading rate and the configuration of a semi-pilot modular microbial electrolysis cell (MEC) on the energy consumption during domestic (dWW) wastewater treatment. The MEC reactor consisted of twin tubular units hydraulically connected in series and was able to reduce up to 85% of the chemical oxygen demand (COD) concentration of the influent dWW at a relatively low energy consumption (1.6 kW h kg-COD(-1)). Hydrogen production was limited by the reduced amounts of organic matter fed into the reactor and the poor performance of the cathode. Overall, the results identified both an organic loading rate (OLR) threshold that makes the use of MECs for dWW treatment feasible in terms of energy consumption and COD removal efficiency and an OLR threshold that justifies the operation of two MECs in series to provide the required degree of COD removal.

Pathologic changes in the retina and optic nerve are observed in patients with Alzheimer´s disease (AD), even in early stages of the dementia. In our clinical ophthalmology practice, we use optical coherence tomography (OCT), a noninvasive, rapid, objective, and reliable technology that enables for quantification of the retinal nerve fiber layer (RNFL), namely the retinal ganglion cell axons that eventually form the optic nerve. The opportunity to analyze a part of the central nervous system by such a simple exploration led to several studies demonstrating thinning of the RNFL and central retina in AD patients compared with healthy subjects. Here we present some of our investigations in AD patients using Spectral Domain-OCT. Our results suggest that axonal loss secondary to pathologic alterations in the brains of AD patients can be observed by OCT. We also analyzed the association between retinal and RNFL thicknesses and neurologic characteristics, disease duration and severity, and found that mean RNFL thickness was significantly correlated with disease duration, indicating that the progression of AD is associated with a progressive loss of ganglion cells.

The marine environments on the shallow shelf of La Guajira, Colombian Caribbean. A brief description of seven benthic environments found in La Guajira’s shallow continental shelf from Boca de Camarones to Cabo de la Vela between 3 to 20 m depth is presented. Cover percentage of main benthic components, organic matter proportion in sediment, and main organisms observed in each environment are listed. The dominant environment was “arenal” (sandy bottom) covering 47% of total area sampled, whereas most species were observed in the environments “fondo mixto” (mixed bottom), “cascajo compuesto” (composed gravel) and “corales y esponjas sobre cascajo” (corals and sponges on gravel).

We evaluated the effect of hIFNβ gene transfer alone or in combination with different antineoplastic drugs commonly used in cancer treatment. Five human tumor-derived cell lines were cultured as monolayers and spheroids. Four cell lines (Ewing sarcomas EW7 and COH, melanoma M8 and mammary carcinoma MCF-7) were sensitive to hIFNβ gene lipofection. Although this effect appeared in both culture configurations, spheroids showed a relative multicellular resistance (insensitive colon carcinoma HT-29 excluded). EW7 and M8 hIFNβ-expressing cells were exposed to different concentrations of bleomycin, bortezomib, carboplatin, doxorubicin, etoposide, methotrexate, paclitaxel and vincristine in both configuration models. In chemotherapy-sensitive EW7 monolayers, the combination of hIFNβ gene and antineoplastic drugs displayed only additive or counteractive (methotrexate) effects, suggesting that cytotoxic mechanisms triggered by hIFNβ gene lipofection could be saturating the signaling pathways. Conversely, in chemotherapy-resistant EW7 spheroids or M8 cells, the combination of hIFNβ with drugs that mainly operate at the genotoxic level (doxorubicin, methotrexate and paclitaxel) presented only additive effects. However, drugs that also increase pro-oxidant species can complement the antitumor efficacy of the hIFNβ gene and clearly caused potentiated effects (bleomycin, bortezomib, carboplatin, etoposide and vincristine). The great bystander effect induced by hIFNβ gene lipofection could be among the main causes of its effectiveness, because only 1 or 2% of EW7 or M8 hIFNβ-expressing cells killed more than 60 or 80% of cell population, respectively.

Vegetable oils (Vo) are an alternative to fish oil (Fo) in aquaculture feeds. This study aimed to evaluate the effect of dietary soybean oil (Vo diet), rich in linoleic acid, and of dietary fish oil (Fo diet) on the development of spinal deformities under bacterial lipopolysaccharide (LPS)-induced chronic inflammation conditions in Atlantic salmon, Salmo salar L. Fish [25 g body weight (BW)] were fed the experimental diets for 99 days. On day 47 of feeding (40 g BW), fish were subjected to four experimental regimes: (i) intramuscular injections with LPS, (ii) sham-injected phosphate-buffered saline (PBS), (iii) intraperitoneally injected commercial oil adjuvant vaccine, or (iv) no treatment. The fish continued under a common feeding regime in sea water for 165 more days. Body weight was temporarily higher in the Vo group than in the Fo group prior to immunization and was also affected by the type of immunization. At the end of the trial, no differences were seen between the dietary groups. The overall prevalence of spinal deformities was approximately 14% at the end of the experiment. The Vo diet affected vertebral shape but did not induce spinal deformities. In groups injected with LPS and PBS, spinal deformities ranged between 21% and 38%, diet independent. Deformed vertebrae were located at or in proximity to the injection point. Assessment of inflammatory markers revealed high levels of plasma prostaglandin E₂ (PGE₂) in the Vo-fed and LPS-injected groups, suggesting an inflammatory response to LPS. Cyclooxigenase 2 (COX-2) mRNA expression in bone was higher in fish fed Fo compared to Vo-fed fish. Gene expression of immunoglobulin M (IgM) was up-regulated in bone of all LPS-injected groups irrespective of dietary oil. In conclusion, the study suggests that Vo is not a risk factor for the development of inflammation-related spinal deformities. At the same time, we found evidence that localized injection-related processes could trigger the development of vertebral body malformations.

Consumption of minimally processed vegetables has increased in recent years. However, despite these advantages, minimally processed commodities have the limitation of rapid quality damage deterioration and short shelf life due to tissue damage caused by processing. The effect of different sanitizing treatments, as alternatives to chloride, the evaluation of the effect of storage temperature and time, and apparent shelf life, was investigated on the quality of minimally processed garlic. Garlic cloves were peeled, washed in tap water at 0°C, cut into small cubes, and submitted to the following treatments: i) hypochlorite (OCl - ), ii) hydrogen peroxide (H 2 O 2 ), iii) lactic acid, iv) calcium lactate, and v) ultraviolet radiation (UV-C), and centrifuged to remove excess water, when needed. The samples were stored at 4, 8 and 12°C, up to four days (96h). Several parameters were determined for these conditions: respiration rates (RO 2 and RCO 2 , ml/kg/h), pH, dry matter (%), total soluble solids (°Brix), and colour (CIE-Lab). Of the different sanitizing treatments studies, the application of hydrogen peroxide (H 2 O 2 ), in garlic cubes, was the most advantageous, mainly by the reduced values of respiratory rate over storage time and the retention of the brightness. Once the best sanitizing treatment was chosen, aiming at the retention of quality of minimally processed garlic, a more detailed storage effect was studied by checking the shelf life of garlic when stored at different temperatures: 4, 8, 12, 16 and 20°C. It was found that the apparent shelf life decreases with increasing storage temperature. For the lowest temperature, 4°C, the garlic reached approximately 268 hours of shelf life, about eleven days.

This study is the first to report the occurrence of intimal thickening of coronary arteries in a holocephalan, namely the rabbitfish, Chimaera monstrosa. The sample studied consisted of five hearts from rabbitfish with body weights ranging between 12 g and 1116 g. The specimens were fixed in formalin, in methanol:acetone:water (MAW), or in paraformaldehyde and were examined by brightfield and polarization light microscopy. Coronary arteries from three larger animals displayed focal intimal thickenings, which were located in the left main coronary artery trunk, at the level of the cono-ventricular junction, and in several intramyocardial ventricular arteries. The vascular changes were characterized by myointimal proliferation, breakage or absence of the inner elastic lamina, and, in one case, by increased collagen within the myointimal proliferation. Taking into account the severity of the coronary arterial changes, their location, and the body weight of the affected animals, we conclude that (1) these changes are age-related in the rabbitfish and (2) local intense mechanical tension seems to be an important factor in their formation in this species.

The National Institute of Standards and Technology (NIST) certifies a variety of standard reference materials (SRM) to address specific aspects of instrument performance for divergent beam diffractometers. This paper describes SRM 640d, the fifth generation of this powder diffraction SRM, which is certified with respect to the lattice parameter. It consists of approximately 7.5 g silicon powder specially prepared to produce strain-free particles in a size range between 1 and 10 μm to eliminate size-broadening effects. It is typically used for calibrating powder diffractometers for the line position and line shape. A NIST built diffractometer, incorporating many advanced design features, was used to certify the lattice parameter of the silicon powder measured at 22.5 °C. Both type A, statistical, and type B, systematic, errors have been assigned to yield a certified value for the lattice parameter of a=0.543 159±0.000 020 nm.

Measurement, analysis, and modeling of respiration rate (RR) of fresh produce are fundamental for the engineering design of MAP. This study investigates the effect of type of cutting (sliced in circular shape, batons in rectangular shape, and shredded into thin strips) on the respiration rate of carrots at different temperatures (4, 8, 12, 16, and 20 degrees C) with ambient atmosphere. The higher respiration rates were found for shredded carrots and the lowest for whole carrots at all the temperatures tested. The RR increased from 9 +/- 1 to 26 +/- 3, 10 +/- 1 to 53 +/- 2, 11 +/- 1 to 55 +/- 2, and 18 +/- 1 to 75 +/- 3 mL of O(2) per kilogram hour for whole, sliced, baton, and shredded carrots, respectively, as the temperature increased from 4 to 20 degrees C. On an average, RO2 and RCO2 were increased by 85% and 64%, 100% and 72%, and 151% and 124% for sliced, baton, and shredded carrots, respectively, compared to the RR values of whole carrots. The temperature dependence of RR followed an Arrhenius-type relationship for all types of carrots, with activation energies in the range of 35 +/- 3 to 62 +/- 2 kJ/mol. Type of cut was the major factor for both RO2 and RCO2, with shredded carrots having the highest rates and whole carrots the lowest. RR of whole carrots did not vary during storage, whereas it increased for cut carrots and especially for shredded carrots. The respiratory quotient (RQ) increased with temperature and did not vary during storage in all types of carrots, except the RQ of whole carrots decreased significantly over time.

Trace element determination can be applied in forensic medicine to diagnose the cause of death. Drowning is the second leading cause of death from unintentional injury. Despite the many diagnostic methods used, the post-mortem diagnosis of drowning continues to be one of the most difficult in forensic pathology. Strontium is a highly sensitive marker of water aspiration in a liquid medium rich in this metal. The aims of this study were to confirm the diagnostic value of strontium in cases of drowning compared with other causes of death, to analyse factors that could affect its concentration and to ascertain the sensitivity and specificity of strontium in right and left ventricles and peripheral serum for the post-mortem diagnosis of drowning. We studied 120 cadavers selected from medico-legal autopsies with different causes of death. Strontium (Sr) levels were measured in the serum (left and right ventricles and peripheral vein) of all cadavers and, in the case of drowning, in the water medium itself, by using Zeeman AAS. Our results confirm the usefulness of blood Sr levels for diagnosing seawater and freshwater drowning, although great care should be exercised in the latter case.

Kinins are important vasoactive peptides, but the role of the B1 receptor subtype in the vascular control is poorly understood. This study analyzed the nitric oxide (NO) release, L-arginine (L-Arg) uptake and the expression of the cationic amino acid transporter (CAT) -1 in endothelial cells obtained from B1 receptor knockout (B1-/-) and wild type (WT) mice. NO production was assessed through a fluorescent dye in living cells stimulated with acetylcholine. L-Arg uptake was determined indirectly in the culture medium by HPLC, in the presence or absence of the CAT-1 blocker N-ethylmaleimide (NEM). CAT-1 mRNA levels and protein expression were determined by qPCR and western blot, respectively. NO release was significantly reduced in B1-/- when compared to WT cells. This result was accompanied by a decreased rate in the L-Arg uptake by B1-/- cells. Incubation with NEM impaired the L-Arg uptake in WT, but had no effect in B1-/- cells. Protein expression and mRNA levels for CAT-1 were reduced in B1-/- in comparison to WT cells. These findings suggest an important role of the endothelial B1 receptor in the vascular control by interfering with CAT-1 expression, L-Arg uptake and NO release.

Platinum(iv) complexes take advantage of the exclusive conditions that occur within the tumor to carry out their cytotoxic activity. On the other hand, silk fibroin has natural properties which make it very interesting as a biomaterial: high biocompatibility, biodegradability, low immunogenicity, high cellular penetration capacity and high reactive surface. Herein we report the preparation of silk fibroin nanoparticles (SFNs) loaded with the hydrophobic Pt(iv) complex cis,cis,trans-[Pt(NH(3))(2)Cl(2)(O(2)CC(6)H(5))(2)] (PtBz). Only a small fraction of the loaded PtBz is released (less than 10% after 48 h). PtBz-SFNs trigger strong cytotoxic effects against human ovarian carcinoma A2780 cells and their cisplatin-resistant variant A2780cisR cells. Interestingly, PtBz-SFNs are very cytotoxic (nanomolar IC(50) values) toward the triple negative breast tumor cell line MDA-MB-231, and also toward SK-BR-3 and MCF-7, while maintaining an excellent selectivity index.

Measurement and modelling of the respiration rate of fresh-cut produce is vital for the engineering design of modified atmosphere packaging systems. In this work the closed system methodology was used to measure the respiration rate (O 2 consumption and CO 2 production) of shredded carrots as a function of time and temperature. The experiments were carried out at 4, 8,12,16 and 20°C for 144, 108, 90, 72 and 54 hours, respectively, during storage under ambient atmosphere. The effect of temperature on respiration rate was well described by an Arrhenius type equation. The respiratory quotient was approximately constant over time, but it showed a polynomial increase with temperature, ranging from 0.51 to 0.83. Under all the experimental conditions tested, respiration rate went through an initial lag phase before increasing sharply as storage time progressed. This effect was enhanced with increasing temperature and was well described by a Weibull model with a shape constant independent of temperature and with a time constant decreasing with temperature according to an Arrhenius type equation. The rate of O 2 consumption at time zero and at equilibrium, at a reference temperature of 12°C, were estimated to be 24±1 and 118±7 mL.kg -1 .h -1 , respectively. The time constant at the same temperature was 52±5 h and the shape constant was 1.6± 0.1. The activation energy, 79±1 kJ.mol -1 , was the same for both the dependence of the time constant and of respiration rate on temperature, and was within the normal range for fresh produce stored in ambient air.

Fabry's disease is the second most prevalent lysosomal storage disorder after Gaucher's disease. It occurs as the result of a deficit in the alpha-galactosidase A enzyme. The gene coding for it is located on the long arm of the X chromosome (Xq22.1). This deficit causes the gradual accumulation of a glycosphingolipid. The main substance accumulated is globotriaosylceramide (Gb3). This accumulation leads to pain and angiokeratomas, and to cardiac, cerebral, and vascular involvement as the disease progresses. The treatment of Fabry's disease has so far only been symptomatic; however, new advances have now made it possible to prescribe alpha-galactosidase replacement therapy, which not only improves symptoms, but also enhances these patients' quality of life and lowers mortality. In this paper we review the status of Fabry's disease and we report the follow-up of a family with Fabry's disease, with some members receiving replacement therapy with alpha-galactosidase A and demonstrating good progress.

The present study was undertaken to investigate the possibility that high egg vitamin A (VA) status in combination with elevated egg incubation temperatures may cause deformities in Atlantic salmon, Salmo salar L. Egg batches selected for their total VA concentration were exposed to low (normal, 8 degrees C) or elevated (14 degrees C) egg incubation temperatures. Temperature was the main factor causing bone deformities such as warped gill opercula, fin and jaw deformities, but not for the development of spinal deformities where all groups displayed a 'baseline' occurrence of mild deformity (decreased vertebral size in the cephalic region) and no systematic variation in the occurrence of serious spinal deformities (fused vertebrae). A possible effect of egg incubation temperature fluctuation was found for the groups reared at low temperatures. An indication of a negative effect of elevated egg VA status for the development of organ deformities such as missing septum transversum and situs inversus was found in addition to temperature effects, however, no firm conclusions could be drawn from the present data. The phenotypes for temperature-induced deformities resembled the phenotype of VA-induced deformities, but no clear conclusions on the causality of the deformities found in the present study could be drawn. Egg incubation temperatures, both absolute temperature and temperature variations, should therefore be strictly controlled.

The cell wall-associated glyceraldehyde-3-phosphate dehydrogenase (cwGAPDH) activity in Saccharomyces cerevisiae increases (two- to 10-fold, depending on the strain) in response to starvation and temperature upshift. Assays using transformants carrying pTDH, a yeast centromer derivative plasmid containing the Candida albicans TDH3 gene (encoding GAPDH) fused in frame with the yeast SUC2-coding region for internal invertase, showed that starvation and/or temperature upshift result in a similar increase in both cwGAPDH and cell wall-associated invertase activities. In addition, this incorporation of GAPDH protein into the cell wall in response to stress does not require (i) de novo protein synthesis, indicating that preexisting cytosolic enzyme is incorporated into the cell wall, (ii) nor the participation of the ubiquitin yeast stress response system, as no differences were observed between wild-type and polyubiquitin-depleted (Deltaubi4) strains.

The action of electromagnetic fields (EMF) on different pathways related to cell physiology, proliferation, toxicity of chemicals, gene expression, etc., are currently being investigated although the results are still not conclusive and even conflicting. In laboratory and animal studies, EMF has been found to produce a great variety of effects such as: increase in ornithine decarboxylase activity in breast, increase in beta-galactosidase gene expression and oncogene transcription after exposure to 50/60 Hz. Animal studies have shown that the use of EMF can enhance drug delivery across biological barriers (rat abdominal skin), using benzoic acid as the drug candidate. It has been reported by different authors that pulsed EMF (PEMF) can produce alterations in antineoplastic drugs potency. In the present study, we investigated the effects of PEMF on methotrexate cytotoxicity in MCF-7 breast cancer cells and the effects with simultaneous exposure to FeCl3. The data presented in the current report indicate that PEMF (25 Hz, 1.5 mT) do not induce modulation of the action of methotrexate (with and without iron-III) in MCF-7 cells when they are exposed to PEMF for 2 h/day during 3 days.

Resumen Resumo Industrial white wines from Torrontes grapes were elaborated. The must was subdivided in two lots, and each one was inoculated with different commercial yeast, but submitting to the same steps and conditions of vinification. In the final wines, the chemical and sensorial analysis were carried out, and the volatile compounds extracted by liquid-liquid extraction with dichloromethane and subsequent injection into a gas chromatograph coupled to a mass spectrometer were also determined. The chemical results did not show significant differences between the two wines. However, the sensorial and aromatic analysis confirmed the influence of the employed yeast. Independently of this, it was possible to confirm that this white variety permit to elaborate quality wines. © 2002 Altaga. All rights reserved. A partir de uvas de la variedad Torrontes en su momento optimo de maduracion, se ha elaborado vino monovarietal a escala industrial. El mosto se ha subdividido en dos lotes y cada uno ha sid...

We have investigated the expression of TLR2 and Dectin-1 in retinal microglia and their involvement in Candida albicans phagocytosis using a cytometric approach. The expression of both receptors has been demonstrated in CD11b+ retinal cells. Phagocytosis of pHrodo-labelled C. albicans yeasts by microglial CD11b+ cells of C57BL/6 mice was inhibited both by the Dectin-1 antagonist laminarin and anti-Dectin-1 antibodies, whereas phagocytosis of yeasts by retinal microglia of TLR2 KO mice was unaffected. These data indicate that phagocytosis of C. albicans yeasts by retinal microglia is mediated by Dectin-1, whereas TLR2 does not play a significant role in this process.

Chemical EOR is starting to pick-up in the industry in the last 10 years due to the high oil cost and lower chemical costs. Preparing the solution for injection is the well established part of the process. However, treatment of the fluids coming from chemical flooded projects is one of the main risks associated with Chemical EOR processes. There are a number of processing difficulties which is caused by the back produced chemicals. Including tighter emulsions, heater fouling and other water treatment challenges. The back produced polymer is recognized as a risk that need to be addressed and mitigated as early as possible for any polymer project. In a field in the Sultanate of Oman, a polymer flood project was initiated early 2010. As part of the project, induced gas flotation and filtration units were installed in order to treat the produced water to the required specification for polymer solution preparation and injection. The required specification is 5 ppm (w) OIW and 2 ppm (w) TSS at the outlet of the filtration stage. This specification is required for polymer preparation and water injection. The molecular weight of the polymer coming back from the reservoir was measured to be in the range of 7 to 10 million Dalton molecular weight. Induced gas flotation technologies are accelerated gravity separation process. If the viscosity of the continuous phase increases, the raising velocity of the oil droplets reduces. It is then very essential for the viscosity of the continuous phase (water) to be maintained. It was found that the performance of the flotation cell decreases dramatically if the viscosity of the water increases more than 1.5-2 cP (at 7.0 s-1 shear rate) by using bench-top IGF trials. Mechanical and chemical means of breaking the HPAM polymer is investigated in this paper to decrease the viscosity of the produced water to a level that will enable the flotation technology to maintain performance to allow a method to be used in the field where these conventional technologies has been already installed. A success criteria was set which is the ability of the method to reduce the viscosity to the range of 1.5 – 2 cP. In terms of mechanical means to break the polymer, it was found that shearing through valves by differential pressure of 40 bars decreases the viscosity to about 2 cP using both higher molecular weight polymer or lower molecular weight polymer and it was more effective than 3-stages centrifugal pump. The main disadvantage of the mechanical shearing is the formation of smaller oil droplet through the shearing and smaller oil droplet which means slower raising velocity in the flotation cells. An attempt was carried out to quantify the effect of the pressure drop on the droplet size distribution. However, the starting droplet size was already in the range of 10 micron. It was observed that there is a small reduction in the droplet size from 10 micron to around 7 microns when the pressure drop is about 40 bars. In terms of chemical means to break the polymer, Sodium hypochlorite was the most effective chemical to break the HPAM polymer. The required dosage rate is in the range of 50 −100 ppm to achieve 1.5-2 cP (at 7.0 s-1 shear rate). In the presence of H2S in the water, it was observed that the dosage rate increases to about 500-1,000 ppm which makes it uneconomical to be implanted in the field. The oxidizer preferentially reacts with H2S to form a colloidal suspension.

Pseudoboehmite nanoparticles synthesized through the desulfation of Al2(SO4)3 were used to investigate the reinforcement of commercial porcelain stoneware. Fractured specimens investigated by SEM suggest that the added pseudoboehmite precursor generated a nanometric primary mullite phase dispersed in the porcelain glassy phase that limited and stopped the intergranular crack propagation. The porcelain modulus of rupture increased twice the value of the modulus of rupture (108 MPa) as compared with that samples without pseudoboehmite additions. Pseudoboehmite also led to increased densification of porcelain stoneware bodies up to 1250°C as shown by thermodilatometry data.

The hypersensitive response (HR), elicited when resistant hosts are infected by incompatible races of biotrophic fungi, has been researched extensively. New studies on host responses to necrotrophic fungi are beginning to show that when the HR occurs in hosts colonized by necrotrophs, fungal growth is accelerated rather than retarded. We review current knowledge about how necrotrophs survive in host plants in which the HR is expressed. We discuss how necrotrophs cope with the environmental factors formed as a result of the HR. Necrotrophs contain an array of enzymes, which can help in exploiting the hostile environment in order to colonize the host and to remove or inactivate active oxygen species (AOS). Among this array of enzymes are superoxide dismutase (SOD), peroxidases, catalase, and perhaps laccases and polyphenol oxidases. Of these, only SOD and catalase have been studied in any detail. The precise significance of SOD and catalase in host invasion and fungal resistance is still not adequately known. The importance of different peroxidases is also still far from clear. We speculate that AOS species may trigger the response of necrotrophs to the host environment.

The amount and rate of soil N mineralization often influences the productivity and persistence of a grass-legume mixture. This research investigated soil N availability in monoculture and binary mixtures of alfalfa (Medicago sativa L.) or red clover (Trifolium pratense L.) with eastern gamagrass [Tripsacum dactyloides (L.) L.] on sandy and clay loam soils near Manhattan, KS. Soil inorganic N and in situ net N mineralization were monitored monthly during the growing seasons of 1996 and 1997. Soil inorganic N was two- to threefold higher with alfalfa, red clover, and gamagrass-alfalfa mixture than with gamagrass in monoculture at the end of 1996. At the midseason of 1997, soil inorganic N was three- to ninefold higher at the clay loam site, but at the sandy site, only alfalfa monoculture was three- to fivefold higher than the other treatments in both years. Soils under alfalfa at both sites in 1997 had the highest cumulative net N mineralized (35-100 kg N ha -1 yr -1 ), followed by the gamagrass-legume mixtures (15-62 kg N ha -1 yr -1 ) and then the gamagrass monoculture treatment (2-15 kg N ha -1 yr -1 ). A high correlation (r 2 > 0.9, P < 0.05) was found between C/N ratio of the aboveground biomass and the total net N mineralized in the 2nd yr for both sites, suggesting that litter quality is an important driving variable on N mineralization. Our results emphasize the importance of forage legumes in maintaining soil quality and productivity and quality of forage mixtures.

The present paper evaluates the solderability of three discontinuously reinforced aluminium matrix composites. The tested composites were an aluminium alloy of the 2000 series (AA2014) reinforced with different percentages of silicon carbide particles (6, 13, and 20 vol.-% respectively). A similar study was carried out on the unreinforced aluminium alloy for comparative purposes. Three low temperature filler alloys of the Zn–Al system were used for soldering. Drop formation tests were performed to evaluate the wettability of the molten filler alloys and sample joints (single overlap specimens) were produced to determine solder penetration in the joint clearance. Microstructural studies of the joints were carried out to determine the effects of the solid reinforcement particles on molten pool behaviour and solidification mechanisms.

The present study shows the application of gas chromatography for the determination of the concentrations of a wide range of compounds responsible for the organoleptic and sanitary characteristics of distilled spirits. The aim of this research is to relate the concentration of methanol, higher alcohols, esters, organic acids and aldehydes in several distillates to the storage time of grape pomace and the size and material of the container. The results obtained can be useful in deciding which fermentation and storage conditions are more suitable for ensuring high quality of the grape pomace and thus of the spirits obtained from them. For this purpose six distillates from raw material stored under different conditions were analysed.

Albarino and Loureira grapes were collected during maturation in 1998 and free and bound volatile compounds from the grapes were studied to estimate and compare their aromatic potential. After solid-phase extraction monoterpenols, norisoprenoids, terpenic hydrocarbons, and some alcohols were detected and quantified by GC with FID.

The interfacial reactions in an aluminium alloy composite (AA2009) reinforced with 15% volume of SiC whiskers were studied. The composite was subjected to a simulated casting process to analyse its response under different melting conditions. The different reaction mechanisms between the SiC whiskers and both the molten aluminium and their alloying elements (Cu, Mg, and Fe) are discussed. The high aspect ratio (l/d) of the reinforcement is the main microstructural factor, which controls both reactivity and wettability between the molten matrix and the SiC. Tested specimens showed very great Si-enrichment of the matrix around SiCw which produced an isothermal solidification and stopped the interfacial reactions. Formation of binary aluminium carbide (Al4C3) during the melting cycles was also detected, especially for temperatures higher than 800 °C, produced by a dissolution-precipitation mechanism. Nucleation of the Al4C3 crystal was favoured both on the lateral whisker surfaces and on oxide particles (Al2O3, MgO) present in the aluminium matrix. Transmission Electron Microscopy and Electron Diffraction (TEM-ED) studies made it possible to identify both the nature and the structure of the different interfacial products generated during casting.

The acquisition of resistance to anticancer agents used in chemotherapy is the main cause of treatment failure in malignant disorders, provoking tumours to become resistant during treatment, although they initially respond to it. The main multidrug resistance (MDR) mechanism in tumour cells is the expression of P-glycoprotein (P-gly), that acts as an ATP-dependent active efflux pump of chemotherapeutic agents. Furthermore, an increased detoxification of compounds mediated by high levels of glutathione (GSH) and glutathione S-transferase (GST), has been found in resistant cells. We developed a study aiming to evaluate the evolution of the main drug resistance markers in tumour cells: P-gly, GSH and GST, during the acquisition of resistance to colchicine, for the purpose of studying the adaptation process and its contribution to the MDR phenomenon. A human colon adenocarcinoma cell line was exposed to colchicine during 82 days, being P-gly, GSH levels and GST activity evaluated by flow cytometry, spectrofluorimetry and spectrophotometry, during exposure time. P-gly and GSH levels increased gradually during the exposure to colchicine, reaching 2.35 and 3.21 fold each. On day 82, GST activity increased 1.84 fold at the end of the exposure period. Moreover, an increment in drug cross-resistance was obtained that ranges from 2.62 to 5.22 fold for colchicine, vinblastine, vincristine and mitomycin C. The increments obtained in P-gly, GSH and GST could probably contribute to the MDR phenomenon in this human colon adenocarcinoma cell line.

Behavioral experiments were conducted to examine the role of the cholinergic receptor-agonist muscarine or its antagonist homatropine on the mating behavior of sexually experienced male rats. Male copulatory behavior was recorded after intrathecally administered saline, muscarine (7.5 microg), or homatropine (25 microg). Changes in copulatory behavior were assessed by the following parameters: intromission latency, intromission frequency, intercopulatory interval, ejaculation latency, and postejaculatory interval. Intromission frequency, intercopulatory interval, and ejaculation latency were decreased significantly by muscarine. Intrathecal homatropine decreased the number of copulating animals (five out of 13). In the five animals that were able to ejaculate after homatropine, intromission latency, intercopulatory interval, and ejaculation latency increased significantly. The effects of both drugs on locomotion were also tested. Muscarine induced no significant changes in locomotion compared with saline. A significant increase in locomotion was found after homatropine treatment. These results suggest that acetylcholine, acting at spinal-cord muscarinic receptors, may be involved in ejaculation.

The amounts of intra- and extracellular guaiacol peroxidase, ascorbic peroxidase, glutathione peroxidase, superoxide dismutase, laccase, and catalase present in Botrytis cinerea, cultured in three different media: Kovac synthetic medium, Sabouraud fluid medium, and a medium containing malt extract, were determined. The activity of two enzymes, ascorbic peroxidase and glutathione peroxidase, has not been previously described in B. cinerea. The detected amount of the enzymes showed considerable variability in the three different culture media. The presence of an array of enzymes capable of metabolizing hydrogen peroxide, whose levels are determined by the conditions under which the fungus grows, shows that B. cinerea is well equipped to contend with the occurrence of host-produced active oxygen species.