Fragmentation of propionitrile (CH3CH2CN) by low energy electrons.

Propionitrile (CH3CH2CN, PN) is a molecule relevant for interstellar chemistry. There is credible evidence that anions, molecules, and radicals that may originate from PN could also be involved in the formation of more complex organic compounds. In the present investigation, dissociative electron attachment to CH3CH2CN has been studied in a crossed electron-molecular beam experiment in the electron energy range of about 0-15 eV. In the experiment, seven anionic species were detected: C3H4N-, C3H3N-, C3H2N-, C2H2N-, C2HN-, C2N-, and CN-. The anion formation is most efficient for CN- and anions originating from the dehydrogenation of the parent molecule. A discussion of possible reaction channels for all measured negative ions is provided. The experimental results are compared with calculations of thermochemical thresholds of the detected anions.

Effects of early contrast-enhanced computed tomography on clinical course and complications in patients with acute pancreatitis.

PURPOSE: To investigate the effect of an early contrast-enhanced computed tomography (CECT) on clinical course and complications of acute pancreatitis (AP). MATERIAL AND METHODS: 58 patients with AP who had at least one CECT examination were analyzed retrospectively. Laboratory as well as clinical data, and results from the assessment of disease severity (CT severity index (CTSI) and its modified (MCTSI) version) were analyzed. The primary endpoint was the development of severe complications, defined as death, respiratory failure, acute renal failure, and the need for invasive interventions. Patients were divided into two groups: an early group (CECT within the first 48 h after the onset of symptoms, n = 32) and a late group (CECT > 48 h after the onset of symptoms, n = 26). Multivariate regression analysis was performed to identify risk factors for severe complications. RESULTS: There were no statistically significant differences between both groups concerning baseline characteristics, CTSI, and MCTSI. Complications occurred more often in the early CECT group (p = 0.008). Multivariate logistic regression analysis identified an early CECT and a severe MCTSI as independent risk factors for the occurrence of severe complications (p = 0.02 and p = 0.002, respectively). CONCLUSION: CECT performed within the first 48 h after the onset of symptoms is associated with an unfavorable outcome in AP.

Lack of association of ALOX12 and ALOX15B polymorphisms with psoriasis despite altered urinary excretion of 12(S)-hydroxyeicosatetraenoic acid.

BACKGROUND: Pro- and anti-inflammatory metabolites of arachidonic acid - eicosanoids - participate in skin homeostasis, affecting the growth and differentiation of keratinocytes. Alterations of 12-lipoxygenase (LOX) and 15-LOX and their metabolites have been described in the epidermis of patients with psoriasis, but systemic production of 12-LOX and 15-LOX eicosanoids has not been studied in the disease. OBJECTIVES: To ascertain the frequencies of the genetic variants ALOX12 rs1126667 and ALOX15 rs11568070 in cases and controls, and to compare urinary metabolites of 12(S)-hydroxyeicosatetraenoic acid (HETE) between patients with psoriasis and healthy controls. METHODS: Patients with psoriasis (n = 200) were stratified depending on the severity of their dermal lesions. Genotyping was performed using a 5'-nuclease real-time assay. The concentrations of 12(S)-HETE, its metabolites and 15(S)-HETE were determined in urine samples using high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Tetranor-12(S)-HETE metabolite excretion was significantly higher in urine of patients with psoriasis, while excretion of 12(S)-HETE was decreased. Neither 12(S)-HETE nor tetranor-12(S)-HETE correlated with the type of disease or severity score. No difference in urinary 15(S)-HETE was found between the study groups. Genotype distribution of the ALOX12 rs1126667 or ALOX15 rs11568070 polymorphisms did not discriminate for the disease or its severity. CONCLUSIONS: Systemic metabolism of 12(S)-HETE is accelerated in psoriasis because excretion of the tetranor-12(S)-HETE inactivation product is elevated. No correlation with the severity or extent of psoriasis is detectable. We propose that in patients with psoriasis, 12(S)-HETE to tetranor-12(S)-HETE conversion could be at least a marker for this disease, in which inflammation of the skin can induce microsomal beta-oxidation of this eicosanoid.

An association of TLR2­16934A >T polymorphism and severity/phenotype of atopic dermatitis.

BACKGROUND: Toll-like receptor 2 gene (TLR2) ­16934A>T polymorphism has been shown to be associated with severity of atopic dermatitis (AD) as measured using severity scoring of atopic dermatitis (SCORAD) index. Moreover, TLR2­16934A>T polymorphism has been associated with atopy and allergic disorders in farmers' children. OBJECTIVE: The aim of this study was to evaluate an association between TLR2­16934A>T polymorphism and AD phenotype, including disease severity and concomitant atopic diseases, or potential serum markers of AD severity and also to find a molecular background of the clinical associations. METHODS: Genotyping for TLR2­16934A>T polymorphism was performed in 130 consecutive adult ambulatory patients with AD. Total serum (TS) IgE levels, serum tryptase, plasma interleukin-6 and C-reactive protein were measured. In addition, luciferase assay and electrophoretic-mobility shift assay were conducted to assess the effect of ­16934A>T polymorphism on transcriptional activity. RESULTS: There was an inverse association of TLR2­16934TT genotype and/or ­16934T allele with SCORAD, but not with TS IgE, tryptase or inflammatory markers. Interestingly, ­16934AA genotype and/or ­16934A allele were overrepresented in AD patients with concomitant asthma or a family history of atopy. In a subgroup analysis, TLR2­16934A>T polymorphism was associated with SCORAD, asthma, allergic conjunctivitis or family history of atopy in AD patients with TS IgE ≥106 IU/mL but not in those having TS IgE <106 IU/mL. Functional analyses showed that TLR2­16934T allele is associated with higher luciferase activity in human monocytic THP-1 cells and preferential binding of the THP-1-derived nuclear protein. CONCLUSION: TLR2­16934A>T polymorphism could be a genetic predictor of AD severity, the coexistence of asthma or atopic conjunctivitis as well as a family history of atopic diseases, especially in subjects having higher TS IgE. TLR2­16934A>T polymorphism affects transcriptional activity, which may at least in part account for the clinical associations observed for the ­16934A>T polymorphism.

Simultaneous preparation of N2 and CO2 from water nitrates for δ15N and δ18O analysis on the example of the Zemborzycki Reservoir studies.

Nitrates are bioavailable compounds, which are necessary for every living organisms. However, their excess could be harmful, because it could lead to, i.e., methemoglobinemia, formation of carcinogenic nitrosamines and reservoir eutrophication. Isotopic analysis of δ15N and δ18O in nitrates allows to distinguish their different sources. To simplify the way of nitrate source monitoring, we developed a less complex and cheap "off-line" method for nitrate isotopic analysis, in which we obtain both gases required for isotopic analysis of NO3-, N2 for δ15N and CO2 for δ18O measurements, in one procedure. The developed method is based on simultaneous conversion of AgNO3 (mixed with C and placed into PtIr boat) to N2 and CO2 in a glass vacuum apparatus. A small amount of sample (8 mg of AgNO3) required for this procedure and a good reproducibility of the isotopic analysis (better than 0.3‰ for δ18O and 1‰ for δ15N) make this method a useful tool for environmental research. Using the developed method, we analyzed the isotopic composition of N and O in nitrates in the Zemborzycki Reservoir near Lublin (Poland), in 2015. The results indicate a large variation of δ15N (from -1.4 to +37.7‰) and δ18O (from +5.5 to +25.9‰) values in NO3- ions, while the concentration of NO3- varied from 0.2 to 15.3 mg/dm3. These preliminary results suggest that nitrate fertilizers probably are the main source of NO3- pollution. Our study points out the input of manure and/or sewage to the analyzed reservoir in the subsequent periods of sample collection.

Interleukin 25, thymic stromal lymphopoietin and house dust mites in pathogenesis of atopic dermatitis.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in the world. It is characterized by recurrent eczematous skin lesions, fluctuating course and chronic pruritus. Increasing evidence suggest that AD is more common in adults than previously thought. The disease is characterized by an impaired skin barrier, aberrant Th2-type cytokine production and intensive pruritus. Epithelial keratinocytes constitute the first physical, chemical and immunological barrier, classified as a part of the innate defense system. These keratinocytes secrete various factors, e.g. alarmins such as thymic stromal lymphopoietin (TSLP) and interleukin 25 (IL-25). Serum levels of substance P (SP) have been reported to be increased in patients with AD and correlated with itch intensity. Several previous studies reported a positive association between AD severity and house dust mites (HDM) sensitization. The aim of the study was to analyze IL-25, TSLP and SP concentrations in blood serum of adult patients with severe AD, depending on the degree of allergy to HDM. There were 31 adult AD patients enrolled into the study and a control group that consisted of 20 healthy subjects. AD was diagnosed on the basis of Hanifin and Rajka criteria. SCORing Atopic Dermatitis (SCORAD) and visual analogue (VAS) scores were used to assess the intensity of pruritus and blood content of specific IgE to HDM, as well as TSLP, IL-25 cytokines and SP was measured. Our study presents the evidence that IL-25 serum concentration is increased in patients with atopic dermatitis and this cytokine plays an important role in pathogenesis of this disease. HDM could stimulate the release of IL-25 which aggravates the disease severity. Our results corroborate previous findings on the role of TSLP in atopic dermatitis.

Effect of surrounding tissue on propagation of axisymmetric waves in arteries.

A model of an artery consisting of a thin-walled flexible tube filled with a Newtonian incompressible liquid and surrounded by an external viscoelastic tissue is studied. The dispersion relations and attenuation lengths are determined for the lowest axially symmetric propagation modes: the Young, Lamb, and torsional modes. The numerical calculations confirm a low attenuation of the Young mode and a relatively weak dependence of its phase velocity on the elastic parameters of the surrounding medium. The Lamb and torsional modes show a nonzero frequency (a gap) at zero wave vector except for the limiting case of the absence of surroundings. The attenuation of the Lamb mode at zero frequency and the gap frequency turns out to be particularly sensitive to the elastic parameters of the surroundings. However, the spatial attenuation of the Lamb mode extends over a length of the order of 10cm at the viscoelastic parameters corresponding to human tissues. Such lengths are comparable to the size of human organs. Three kinds of local axially symmetric perturbations have been studied, and the corresponding amplitude ratios of the Lamb to the Young mode calculated. The amplitude of the Lamb mode turns out to exceed that of the Young mode by a factor of ten at some frequencies with perturbations involving axial motions. Physiological consequences of this effect are discussed.

Chronic administration of antidepressant drugs increases the density of cortical [3H]prazosin binding sites in the rat.

Administration of antidepressants (imipramine, citalopram) or antidepressant neuroleptics (levomepromazine, chlorprothixene) for 14-24 days enhanced by 20-30% the density of [3H]prazosin binding sites in the membranes from the cerebral cortex of the rat, without significant change in their affinity.

Chronic electroconvulsive treatment enhances the density of [3H]prazosin binding sites in the central nervous system of the rat.

Chronic electroconvulsive treatment (ECT) given daily for 10 days enhanced the density of [3H]prazosin binding sites in the membranes from the spinal cord and cerebral cortex of the rat 24 h after the last shock. Similar effect (investigated only in cortical membranes) was produced by spaced ECT (5 shocks at 72 h intervals). The effect was preceded by a decrease in the density of [3H]prazosin binding sites, observed 2 h after the last shock and disappeared within 48 h.

Electroshock-induced increase in [3H]prazosin binding to cortical membranes in reserpinized rats.

Chronic, spaced electroconvulsive shock (ECS, 6 treatments at 72 h intervals) produced a moderate (16%) increase in the density of [3H]prazosin binding sites to rat cerebral cortical membranes. The increase was of borderline significance (0.1 greater than P greater than 0.05) and KD was not affected. The effect was similar but much more pronounced (increase in Bmax by 38%, P less than 0.01) in rats receiving reserpine pretreatment (4 mg/kg i.p.) 24 h before each ECS. Reserpine produced a transient increase in [3H]prazosin binding 24 h but not 48 h after the last dose, at the time when the ECT effect was measured.

Increase in rat cortical [3H]naloxone binding site density after chronic administration of antidepressant agents.

Given chronically, the first and second generation antidepressants imipramine and citalopram, and antidepressant neuroleptics levomepromazine and chlorprothixene, elevated moderately but significantly (by 15-30%) the density of [3H]naloxone binding sites in rat cerebral cortical membranes. There were only small non-significant changes in Kd values.

Isolation and partial characterization of the trypsin inhibitor from the seeds of Brassica oleracea var. sabellica.

A trypsin inhibitor was extracted from the kale seeds with 0.01 M-HCl, precipitated with ammonium sulphate, and purified by affinity chromatography on immobilized trypsin and ion-exchange chromatography on QAE-Sephadex A-25. The inhibitor, of Mr 8 000, is composed of 64 amino acid residues and contains neither threonine nor methionine. Its isoelectric point is 8.9. In addition to trypsin, the inhibitor acts on subtilopeptidase A and shows a very weak antichymotrypsin activity. The factors modifying the arginine residues inactivate the inhibitor. A modified form of the inhibitor (with a broken reactive site peptide bond) has been isolated in pure form, and its properties were compared with those of the virgin form.

Trypsin inhibitors in bovine lung and pancreas during development.

1. The activity of trypsin inhibitors in lung and pancreas increased with age of the animals. 2. In foetal lung the activity of the basic Kunitz-type inhibitor was 1% that, and in calf lung 5-30% that, found in adult animals. 3. In foetal pancreas the basic Kunitz-type inhibitor was not detected, and in calf pancreas its activity was much lower than in adult animals. The activity of the acidic Kazal-type inhibitor in foetal pancreas was significantly lower than in calf or adult animal.

Antiproteolytic activity of goose pancreas: purification, inhibitory properties and amino-acid sequence of a Kazal type trypsin inhibitor.

A trypsin inhibitor of Kazal type has been isolated from goose pancreas by affinity chromatography on immobilized anhydrotrypsin, anion exchange and reverse phase HPLC. It inhibits bovine beta-trypsin with the association constant (Ka) of 5.99 x 10(8) M-1. The complete amino-acid sequence was determined following CNBr treatment. The protein comprised a total of 69 amino-acid residues, corresponding to a molecular mass of 7.7 kDa. The P1-P'1 reactive site bond of the inhibitor was localized at position Lys25-Met26. The amino-acid sequence of GPTI shows extremely high homology to that of other inhibitors isolated from pancreas of birds.

Protein inhibitors of trypsin from the seeds of Cucurbitaceae plants.

Seven trypsin inhibitors were isolated from the seeds of Cucurbitaceae plants: two from cucumber (Cucumis sativus) and red bryony (Bryonia diotica) and one from figleaf gourd (Cucurbita ficifolia), spaghetti squash (Cucurbita pepo var. (vegetable spaghetti) and water melon (Citrullus vulgaris). The inhibitors were purified by fractionation with ammonium sulphate, followed by ion-exchange chromatography and affinity chromatography using immobilized trypsin or anhydro-trypsin. The homogeneous inhibitors from cucumber and water melon are made up of 32 and 30 amino acid residues, respectively, whereas the remaining ones of 29 residues. All inhibitors contain three disulphide bridges and are free of threonine, phenylalanine and tryptophan. Inhibitors from spaghetti squash and CSTI IIb from cucumber are inactivated by acetylation of free amino groups whereas the remaining ones are inactivated by modification of arginine with 1,2-cyclohexanedione. Thus the P1 residues of the reactive sites of the inhibitors are lysine and arginine, respectively.

Aspartyl proteinase from cucumber (Cucumis sativus) seeds. Preparation and characteristics.

Aspartyl proteinase (EC 3.4.23) from cucumber seeds was purified by ammonium sulphate fractionation, chromatography on immobilized pepstatin and gel filtration on Sephacryl S-200. The preparation obtained, homogeneous on polyacrylamide-gel electrophoresis in acidic and alkaline media, has a molecular mass of 42,000, pI of 5.2, and shows the highest activity with denatured haemoglobin at pH 3.2. The proteinase is stable in slightly alkaline medium, whereas it is inactivated in acidic medium, especially in the presence of NaCl. The enzyme activity is affected neither by the inhibitors of serine proteinases, sulfhydryl-proteinases and metalloproteinases, nor by divalent metal ions, whereas the enzyme is inactivated by the inhibitors of aspartyl proteinases: 1,2,3-epoxy(p-nitrophenoxy)propane, diazoacetyl-DL-norleucine and pepstatin.

Effect of electroconvulsive treatment on cerebral opioid receptors in the rat: changes in delta but not mu receptors.

The rats subjected to repetitive electroconvulsive treatment (ECT; 8 electroshocks within 9 days) the density of specific 3H-D-Ala2, D-Leu5-enkephalin (3H-DADLE) binding sites in the cortical membranes was enhanced by approx. 60%, while the density of specific 3H-naloxone binding sites remained unchanged. In the striatum of rats subjected to ECT the specific binding of 3H-DADLE was reduced by 15%, and no change in 3H-naloxone binding was observed. The density of specific binding sites for either radioligand in the rest of brain remained unaffected by ECT. The results suggest that ECT affects specifically the opioid delta receptors in some brain areas.

Electron ionization study of ammonia micro-clusters

An electron impact ion source on a double focusing sector field mass spectrometer was used to investigate ammonia micro-clusters produced by the adiabatic free jet expansion of ammonia gas. The appearance energies for [NH(3)](n)(+), n

High concentrations of sodium chloride facilitate the use of immobilized chymotrypsin for separating virgin forms of specific trypsin inhibitors.

It has been shown that specific trypsin inhibitors exhibit also antichymotrypsin activity in the presence of high NaCl concentrations. Taking advantage of this phenomenon a simple procedure of separation of the virgin forms of trypsin inhibitors from squash seeds and porcine pancreas (Kazal) was elaborated. In a typical experiment the inhibitor sample was loaded onto immobilized chymotrypsin equilibrated with 5 M NaCl at pH 8. After washing out unadsorbed material the virgin forms of inhibitors could be eluted either with water, buffer pH 8.0 or 0.02 M citrate buffer pH 2.6 containing no NaCl.

Presenting economic information for decision making.

This article identifies and discusses the interest and role of each of the stake-holders in the pharmacoeconomics decision process: sponsors, researchers, medical and economics experts, and decision-makers. In addition, the different publication strategies available to facilitate successful presentation of pharmacoeconomic data are reviewed. It is apparent that the presentation of pharmacoeconomic data will be successful only when clear objectives and an intended target audience are identified at the outset of the study.