Free Release Research Articles

Двохелектронне відновлення нітроароматичних сполук флавінмононуклеотидом. ТФГ розрахункове дослідження

The mechanism for reduction of nitroaromatic compounds by flavin mononucleotide (FMN) was examined at MPWB1K/tzvp level. The solvent effects were calculated using a PCM(Pauling) and SMD(Pauling) solvation models for ions and neutral molecules, respectively. Calculated thermodynamics of the reduction of nitro group to nitroso group suggests consequtive four-steps’ process (electron–proton–electron–proton transfer) where the first proton comes from solution, while the second one – from FMN. Water molecule releases during fourth step of the process. Electron attachment to nitrocompound and electron lose by reduced FMN facilitate the breaking of N–O bond and proton release, respectively. Calculations show that reduction of nitro group to nitroso group in studied nitrocompounds is a thermodynamically feasible with 56–59 kcal/mol Gibbs free energy release. The most easy electron transfer proceeds for TNT (2,4,6-trinitrotoluene) and NTO (5-nitro-2,4-dihydro-3H-1,2,4-triazol-3-one). While the most energy release occurs during proton transfer in case of ANTA (5-amino-3-nitro-1H-1,2,4-triazole).

Triphala herbal extract suppresses inflammatory responses in LPS-stimulated RAW 264.7 macrophages and adjuvant-induced arthritic rats via inhibition of NF-κB pathway

This study sought to explore the mechanism of anti-inflammatory effect of triphala in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and in adjuvant-induced arthritic rats. In stimulated RAW 264.7 cells, triphala (100–300 μg/ml) significantly suppressed production of inflammatory mediators (e.g. TNFα, IL-1β, IL-6, MCP-1, VEGF, NO, PGE2), intracellular free radicals and release of lysosomal enzymes (e.g. acid phosphatase, β-galactosidase, N-acetyl glucosamindase and cathepsin D) in a dose-related manner. With triphala, mRNA levels of genes for pro-inflammatory TNFα, IL-1β, IL-6 and MCP-1, inflammatory iNOS and COX-2 enzymes and NF-κBp65 were down-regulated in the stimulated cells; in contrast, there was up-regulation of heme oxygenase-1 (HO-1) expression. Western blot analyses revealed that triphala suppressed the protein expression of NF-κB p65 and p-NF-κB p65 in the stimulated cells, which subsequently reduced over-expression of TNFα, IL-17, iNOS and COX-2 in a manner similar to that observed with BAY 11-7082, an IκB kinase inhibitor. Immunofluorescence analysis revealed inhibition of p-NF-κB p65 nuclear translocation and COX-2 protein expression caused by triphala. Consistent with these findings, the animal studies presented confirmed that triphala exhibited anti-inflammatory effects in a rat adjuvant-induced arthritis model by reducing of inflammatory mediator (e.g. IL-17, COX-2 and RANKL) expression via inhibition of NF-κB activation. Taken together, the results here demonstrated that triphala has potential anti-inflammatory applications that could be used for the treatment of inflammatory disorders, including rheumatoid arthritis.

BIOLOGICAL CONTROL OF CITRUS WOOLLY WHITE FLY ALEUROTHRIXUS FLOCCOSUS MASK (HOMOPTERA: ALEYRODIDAE) BY CALES NOACKI HOW (HYMENOPTERA: APHELINIDAE) IN SOME TANZANIAN SMALL-SCALE CITRUS ORCHARDS

Calesnoacki How (Hymenoptera: Aphelinidae) wwas released in citrus groves in Muheza (05°10' 0S, 38°46' 0E) and Morogoro (06° 49' 0" S, 37° 40' 0 E) Townships to control Aleurothrixusfloccosus Mask (Homoptera: Alleyrodidae). Sleeve cage and “free release” methods were used to introduce the parasitoid onto selected citrus trees. C. noacki adults and mummies were released at selected sites between 08:00 and 09:30 am on 14th September 1999.
 Adults were first observed 90 days after introduction. They were also recovered from 2nd and 3rd CWWF instars. At Morogoro, CWWF infestations by adults, eggs and nymphs were reduced by between 6 and 12 fold 90 days after release and between 30 and 300 fold 60 months after. At Muheza decreases were between 140 and 700 and 12 and 17 fold, respectively compared. Parasitoid recovery indicated its establishment. Recoveries were also on trees up to two kilometres away from release sites. Parasitoid release was also accompanied by vigour improvement of previously heavily infested citrus trees. This is the first report of successful use of C. noacki for control of A. floccosus in Tanzania, which was prevented from spreading from the original small infestation foci.

The effect of solvent composition on vancomycin hydrochloride and free base vancomycin release fromin situforming implants

The effect of solvent composition on vancomycin hydrochloride and free base vancomycin release from<i>in situ</i>forming implants

Evolution of regional to global paddy rice mapping methods: A review

Paddy rice agriculture plays an important role in various environmental issues including food security, water use, climate change, and disease transmission. However, regional and global paddy rice maps are surprisingly scarce and sporadic despite numerous efforts in paddy rice mapping algorithms and applications. With the increasing need for regional to global paddy rice maps, this paper reviewed the existing paddy rice mapping methods from the literatures ranging from the 1980s to 2015. In particular, we illustrated the evolution of these paddy rice mapping efforts, looking specifically at the future trajectory of paddy rice mapping methodologies. The biophysical features and growth phases of paddy rice were analyzed first, and feature selections for paddy rice mapping were analyzed from spectral, polarimetric, temporal, spatial, and textural aspects. We sorted out paddy rice mapping algorithms into four categories: (1) Reflectance data and image statistic-based approaches, (2) vegetation index (VI) data and enhanced image statistic-based approaches, (3) VI or RADAR backscatter-based temporal analysis approaches, and (4) phenology-based approaches through remote sensing recognition of key growth phases. The phenology-based approaches using unique features of paddy rice (e.g., transplanting) for mapping have been increasingly used in paddy rice mapping. Current applications of these phenology-based approaches generally use coarse resolution MODIS data, which involves mixed pixel issues in Asia where smallholders comprise the majority of paddy rice agriculture. The free release of Landsat archive data and the launch of Landsat 8 and Sentinel-2 are providing unprecedented opportunities to map paddy rice in fragmented landscapes with higher spatial resolution. Based on the literature review, we discussed a series of issues for large scale operational paddy rice mapping.

Characterization and antimicrobial activity of cellulose derivatives films incorporated with a resveratrol inclusion complex

The aim of this study was to develop an active film based on cellulose derivatives (hydroxyethylcellulose and cellulose acetate), while using resveratrol and its inclusion complex with hydroxypropyl-γ-cyclodextrin as active agents. These films were prepared by the casting method. The structural, mechanical, barrier, surface free energy, optical and release properties were analyzed. The antimicrobial activity of these films against Campylobacter jejuni, Campylobacter coli and Arcobacter butzleri was evaluated by the agar diffusion method. The anti-quorum sensing (QS) activity of films was also studied using the biosensor strain Chromobacterium violaceum ATCC 12472. The active films developed in this work besides being transparent, inhibit the growth of the tested strain and had anti-QS activity. This study showed the potential of these active films as a new approach to control the growth of Campylobacter.

Structure modification and extracellular polymeric substances conversion during sewage sludge biodrying process

Biodrying, an economical and energy-saving biomass waste treatment, removes water from waste using the biological heat generated by organic matter degradation. Technical limitations associated with dewatering complicate the biodrying of sewage sludge. This study investigated the sludge alteration associated with its water removal, focusing on sludge form, extracellular polymeric substances, and free water release. An auto-feedback control technology was used for the biodrying; a scanning electron microscope was used to record the morphological change; three-dimensional excitation–emission matrix fluorescence spectroscopy was used to analyze extracellular polymeric substances (EPS) variation, and time domain reflectometry was used to assess the free water release. Over the 20-day biodrying, there was a 62% water removal rate during the first thermophilic phase. Biodrying created a hollow and stratified sludge structure. Aromatic proteins and soluble microbial byproducts in the EPS were significantly degraded. The thermophilic phase was the phase resulting in the greatest free water release.

Indirect Determination of MCPD Fatty Acid Esters in Lipid Fractions of Commercially Available Infant Formulas for the Assessment of Infants’ Health Risk

MCPD esters are intensively investigated food lipid contaminants for over a decade. Concern related to their presence in various types of food products is related to the fact that possible free MCPD release from its esterified form during digestion may lead to elevated daily intake of these toxicants. Special attention should be devoted into powdered infant formulas, which contain significant amounts of refined vegetable oils, likely to contain high amounts of both 3-MCPD and 2-MCPD esters. Infants being fed with this type of food products only may intake risky amounts of these contaminants, which is a matter of great concern. This paper presents the quality assessment of commercially available powdered infant formulas with regard to MCPD esters presence. For estimating the levels of 3-MCPD and 2-MCPD fatty acid esters in lipid fractions of baby foods, methodology involving accelerated solvent extraction (optimized by response surface methodology) followed by SGS “3-in-1” procedure was applied. MCPD esters were detected in 23 per 24 investigated various types of powdered formulas (basic types, anticolic, antireflux, hypoalergic, lactose free, enriched with DHA, for prematures) offered by several suppliers. Detected levels of MCPD esters varied in the range of 0.13–4.80 mg kg−1.

NLRX1 attenuates damage following traumatic brain injury through negatively regulating NF-κB signaling

Abstract Mechanical trauma to the CNS results in the disruption of the cellular microenvironment leading to massive necrotic and apoptotic loss of neuronal and glia populations. The progressive cascade of secondary events, including ischemia, inflammation, excitotoxicity and free radial release contribute to neural tissue damage. Members of the NLR family of pattern recognition receptors are essential mediators of the host immune response. Recently, our lab and others identified a novel sub-group of NLRs that function as negative regulators of inflammation. One of the members of this sub-group, NLRX1, is a potent regulator of interferon, NF-κB, ROS production and autophagy. Thus, we hypothesized that NLRX1 attenuates Traumatic Brain Injury (TBI) through the negative regulation of overzealous innate immune system signaling. To evaluate this hypothesis, we utilized Nlrx1−/− mice in a controlled cortical impact (CCI) injury model. The Nlrx1−/− mice exhibited significantly larger brain lesions and increased motor deficits following CCI injury. We also observed significant proliferation of microglia within the Nlrx1−/− lesions compared to wild type animals. Mechanistically, our data indicates that NLRX1 attenuates TBI progression through the microglia compartment via negative regulation of NF-κB signaling and IL-6 production. Together, our data extends the function of NLRX1 beyond its currently characterized role in host-pathogen defense and identifies this highly novel NLR as a significant modulator of TBI progression.

Heme changes HIF-α, eNOS and nitrite production in HUVECs after simvastatin, HU, and ascorbic acid therapies

The sickle cell disease (SCD) is a hemolytic genetic anemia characterized by free heme and hemoglobin release into intravascular spaces, with endothelial activation. Heme is a proinflammatory molecule able to directly activate vascular endothelium, thus, endothelial dysfunction and vascular disease are major chronic events described in SCD. The aim of this study was to evaluate the production of endothelial nitric oxide synthase (eNOS), nitrite and hypoxia inducible factor alpha (HIF-α) in HUVECs (human umbilical vein endothelial cells) activated by heme in response to simvastatin, hydroxyurea (HU), and ascorbic acid therapies. eNOS and HIF-α production were evaluated by ELISA and nitrite was measured by the Griess technique. The production of HIF-α increased when the cells were stimulated by heme (p<0.01), while treatment with HU and simvastatin reduced the production (p<0.01), and treatment with ascorbic acid increased HIF-1a production by the cells (p<0.01). Heme increased eNOS production, (p<0.01) but showed a heterogeneous pattern, and the lowest concentrations of all the treatments reduced the enzyme production (p<0.01). The nitrite production by HUVECs was enhanced by stimulation with heme (p<0.001) and was reduced by treatment with HU (p<0.001), ascorbic acid (p<0.001) and simvastatin (p<0.01). In summary, our results suggest that the hemolytic vascular microenvironment in SCD requires different therapeutic approaches to promote clinical improvement, and that a combination of therapies may be a viable strategy for treating patients.

Glucose deprivation stimulates Cu(2+) toxicity in cultured cerebellar granule neurons and Cu(2+)-dependent zinc release.

Copper chloride (0.01mM, 2h) did not have significant influence on the survival of cerebellar granule neurons (CGNs) incubated in balanced salt solution. However, CuCl2 caused severe neuronal damage by glucose deprivation (GD). The glutamate NMDA-receptors blocker MK-801 partially and antioxidant N-acetyl-l-cysteine (NAC) or Zn(2+) chelator, N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) almost entirely protected CGNs from this toxic effect. Measurements of intracellular calcium ions using Fluo-4 AM, or zinc ions with FluoZin-3 AM demonstrated that 1 h-exposure to GD induced intensive increase of Fluo-4 but not FluoZin-3 fluorescence in neurons. The supplementation of solution with CuCl2 caused an increase of FluoZin-3, Fluo-4 and CellROX Green (reactive oxygen species probe) fluorescence by GD. The stimulation of Fluo-4 but not FluoZin-3 fluorescence by copper could be prevented partially by MK-801 and as well as CellROX Green fluorescence by NAC at GD. This data imply that during GD copper ions induce intense displacement zinc ions from intracellular stores, in addition free radical production, glutamate release and Ca(2+) overload of CGNs, that causes death of neurons as a result.

Is low-molecular weight iron dextran really the most risky iron?--Unconvincing data from an unconvincing study.

Is low-molecular weight iron dextran really the most risky iron?--Unconvincing data from an unconvincing study.

Breaking the TRPV1‐Calcineurin Interaction as a Novel Means for Pain Control

Targeting the transient receptor potential vanilloid 1 (TRPV1) channel for pain control is complex. Previous efforts in drug discovery resulted in failure since TRPV1 agonists are painful and TRPV1 antagonists cause hyperthermia. Calcineurin is an important TRPV1 protein partner since an interaction of TRPV1 with calcineurin favors TRPV1 channel opening. Therefore as an alternative, we hypothesized by breaking the interaction between TRPV1 and calcineurin, we can indirectly modulate TRPV1 to reduce pain sensation.To test this hypothesis, we used methods including computational biology, peptide synthesis, in vitro, and behavioral pain assays. Based on computational analysis, we discovered a sequence within the TRPV1 C‐terminus that interacts with the calcineurin A subunit. The TRPV1 region forms an alpha coil‐coil, part of the TRPV1 channel inner pore unit, and is evolutionary conserved in mammals. Based on these findings, we synthesized a peptide against this region, linked it to TAT47–57 and called it V1‐cal. In a competitive in vitro calcineurin activity assay, V1‐cal reduced the ability for calcineurin to dephosphorylate a calcineurin substrate as measured by free phosphate release in vitro. Further, we used a carrageenan‐induced inflammatory pain model in male Wistar rats of 10–14 weeks of age. Nociceptive threshold was assessed using the Randall‐Selitto method at baseline and 3 hours after administration of carrageenan. Ten minutes prior to carrageenan, rats were injected intraplantarly with the V1‐cal peptide or saline control. Relative to the control group, rats treated with the V1‐cal peptide had a higher mechanical pain threshold (55±8g vs 36±1g, mean±SEM, n=5/group). Together, these data suggest V1‐cal is an effective therapeutic for pain control by disrupting the TRPV1‐calcineurin interaction.Support or Funding InformationThis work was supported by NIH grant T32 GM089626 to SM.

Optimising methods for community-based sea cucumber ranching: Experimental releases of cultured juvenile Holothuria scabra into seagrass meadows in Papua New Guinea

Hatchery-cultured juveniles of the commercial holothurian, sandfish (Holothuria scabra), were used for release experiments in a variety of marine habitats under traditional marine tenure near Kavieng, Papua New Guinea (PNG). Juveniles of approximately 4g mean weight were released inside 100m2 sea pens installed within seagrass meadows nearby partner communities, under the care of local ‘wardens’. Within each sea pen, varying levels of protection (free release, 1-day cage and 7-day cage) were provided at release in order to determine if short-term predator exclusion improved survival. Ossicles of juvenile sandfish were tagged with different fluorochromes for each treatment and sandfish survival and growth was recorded after release. A range of biophysical parameters were recorded at the four sites. Contrary to expectations, short-term cage protection did not lead to higher survival at three sites, while a fourth site, despite meeting all considered criteria for suitable release habitat, experienced total loss of juveniles. There were significant differences in mean weight of juveniles between sites after four months. Multivariate analysis of biophysical factors clearly separated the sea pen habitats, strongly differentiating the best-performing site from the others. However, further research is needed to elucidate which biophysical or human factors are most useful in predicting the quality of potential sea ranch sites. Methods developed or refined through these trials could be used to establish pilot test plots at potential ranching sites to assess site suitability and provide guidance on the level of animal husbandry required before commencing community sea ranching operations in New Ireland Province, PNG.

Effect of commercial starter cultures on free amino acid, biogenic amine and free fatty acid contents in dry-cured foal sausage

This study assessed the effects of commercial starter cultures on microbial counts, proteolytic and lipolytic changes of dry-cured foal sausage. Four different batches of foal sausage were manufactured: CO batch: control without starter culture; CX batch was fermented with Staphylococcus carnosus + Staphylococcus xylosus + Pediococcus pentosaceus; FL batch with Debaryomyces hansenii + S. xylosus and TH with P. pentosaceus + S. xylosus. The results revealed that the use of starter cultures increase the number of lactic acid bacteria and the total viable counts, while completely reduce the Enterobacteriaceae count compared with CO batch (spontaneous fermentation). The use of starter cultures increases free amino acids release. The CO batch showed the lowest content of free amino acid (952 vs. about 1200 mg/100 g dry matter). Total level of biogenic amines ranged from 61 to 143 mg/kg. Sausages inoculated with TH starter culture displayed the highest accumulation of total biogenic amines. Lipolytic activity was lower in starter-inoculated sausages than in CO batch (8726–9503 vs. 12858 mg of total free fatty acid/100 g of fat). In conclusion, the use of starter cultures contributes to improve the hygienic quality, however, additional studies should be undertaken to understand the effect of lipolysis and proteolysis on the sensory properties of this product.

Oxidized LDL induced extracellular trap formation in human neutrophils via TLR-PKC-IRAK-MAPK and NADPH-oxidase activation

Neutrophil extracellular traps (NETs) formation was initially linked with host defence and extracellular killing of pathogens. However, recent studies have highlighted their inflammatory potential. Oxidized low density lipoprotein (oxLDL) has been implicated as an independent risk factor in various acute or chronic inflammatory diseases including systemic inflammatory response syndrome (SIRS). In the present study we investigated effect of oxLDL on NETs formation and elucidated the underlying signalling mechanism. Treatment of oxLDL to adhered PMNs led to a time and concentration dependent ROS generation and NETs formation. OxLDL induced free radical formation and NETs release were significantly prevented in presence of NADPH oxidase (NOX) inhibitors suggesting role of NOX activation in oxLDL induced NETs release. Blocking of both toll like receptor (TLR)-2 and 6 significantly reduced oxLDL induced NETs formation indicating requirement of both the receptors. We further identified Protein kinase C (PKC), Interleukin-1 receptor associated kinase (IRAKs), mitogen-activated protein kinase (MAPK) pathway as downstream intracellular signalling mediators involved in oxLDL induced NETs formation. OxLDL components such as oxidized phospholipids (lysophosphatidylcholine (LPC) and oxidized 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (oxPAPC)) were most potent NETs inducers and might be crucial for oxLDL mediating NETs release. Other components like, oxysterols, malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) were however less potent as compared to oxidized phospholipids. This study thus demonstrates for the first time that treatment of human PMNs with oxLDL or its various oxidized phopholipid component mediated NETs release, implying their role in the pathogenesis of inflammatory diseases such as SIRS.

Vascular surgery-related organ injury and protective strategies: update and future prospects

Whilst there has been a reduction in the prevalence of peripheral vascular disease worldwide, a significant proportion of the world's growing population is still affected by disease of the aorta, carotid, iliac and lower limb arteries. These if left untreated can result in severe morbidity and mortality. However vascular surgery, the main definitive treatment for such conditions, is associated with subsequent injury to vital organs including the kidneys, heart, brain, intestines and lungs, with a consequent increase in both morbidity and mortality. The current thinking is that the underlying mechanism of injury is direct organ ischaemia and ischaemia induced formation of free radicals, cytokine release and mitochondrial failure. Various methods to alleviate such injuries have been investigated including pre- and postconditioning strategies, pharmacological therapies including volatile anaesthetic and alpha2 adrenoceptor agonist drugs and more recently remote conditioning strategies. Although these interventions have demonstrated some reduction in the biomarkers for organ injury, attempts to translate these benefits into clinical practice have not been successful in terms of morbidity, mortality or length of hospital stay. For this reason, further research is needed in this area to facilitate the translation of the potential interventional benefits from bench to bedside.

Cyanide toxicity during cardiopulmonary bypass with small dose of nitroprusside: a case report.

Sodium nitroprusside (SNP) is an anti-hypertensive drug, commonly used to decrease the systemic vascular resistance and lower the blood pressure. When the amount of cyanide generated by the SNP exceeds the metabolic capacity for detoxification, cyanide toxicity occurs. Under general anesthesia and cardiopulmonary bypass (CPB), it may be difficult to detect the development of cyanide toxicity. In cardiac surgical patients, hemolysis, hypothermia and decreased organ perfusion, which emphasize the risk of cyanide toxicity, may develop as a consequence of CPB. In particular, hemolysis during CPB may cause an unexpected overproduction of cyanide due to free hemoglobin release. We experienced a patient who demonstrated SNP tachyphylaxis and cyanide toxicity during CPB, even though the total amount of SNP administered was much lower than the recommended dose. We therefore report this case with a review of the relevant literature.

More singular? Self-similar dynamics of damage localization and instability in dynamic fracture

Dynamic fracture instability is studied for three characteristic statements: dynamic crack propagation, dynamic fragmentation and failure wave initiation to combine theoretical interpretation and “in-situ” high resolution experimental data for dynamically loaded quasi-brittle materials (PMMA, glasses, ceramics and fused quartz). Specific type of criticality (the structural-scaling transitions) was established in solid with defects in terms of two structural variables: defect density tensor (defect induced strain) and structural scaling parameter. Two critical values for structural scaling parameter were found that separate characteristic nonlinearity of free energy release in damage kinetic equation that allowed one to establish specific self-similar solution (blow-up dissipative structures) responsible for final stage of damage localization and crack initiation. The set of spatial scales of damage localization (that has the image of mirror zones) and corresponding “incubation” time follow from the self-similar solution as the “eigen-values” of non-linear problem. Different scenario of instability of dynamic fracture in mentioned experiments were analyzed as nonlinear dynamic problem in the presence of two self-similar solutions (two attractors): intermediate asymptotical solution for stress field in crack process zone (as the basement for stress intensity factor) and the set of blow-up self-similar solutions for damage localization kinetics playing the role of collective modes of damage localization. Theoretically predicted flicker noise temporal-spatial statistics was found in dynamic experiments for fused quartz and ceramic rod fragmentation combined with fracto-luminescence recording and analysis of fragment statistics. Resonance excitation of blow-up modes allowed explanation of self-similar pattern of multiple spall kinetics (“dynamic branch” under spall) due to “resonance” excitation of blow-up damage localization kinetics.

Design of Checking Phantom for Metrological Certification Tests of 600 L Rectangular Container Monitoring System

New monitoring system for purpose free release of materials into the living environment with a 600 L container counting geometry was designed and developed. Considering that monitoring system is classified as a dedicated measuring instrument the metrological certification is necessary. For purpose of metrological qualification tests the checking verification container (phantom) was proposed and manufactured. The arrangement of the reference sources in the volume of checking container was designed so that it approximates evenly activity distribution considered at efficiency calibration. Description of monitoring system, measurement uncertainty assessment, design of checking container and results of metrological qualification tests are in more detail discussed. Highlights • The procedure for metrological certification of the gamma spectrometry monitoring system based on the twin HPGe detectors with 600 L rectangular container counting geometry was proposed. • The checking container (phantom) containing 24 holes for rod calibration sources evenly mounted through the container in direction of detectors axes was designed and manufactured. • Proposed arranged of holes for rod sources approximate the homogenous distribution of the activity in container volume that is expected during usual measurement.