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.

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.

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.

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.

Association of polymorphic sites in the OCA2 gene with eye colour using the tree scanning method.

A number of genes are considered to affect normal variation in human pigmentation. Recent studies have indicated that OCA2 is the crucial gene involved in the high variation of iris colour present among populations of European descent. In this study, eleven polymorphisms of the OCA2 gene were examined in search of their association with different pigment traits. The evolutionary tree scanning method indicated that the strongest phenotypic eye colour variation is associated with the branch defined by nonsynonymous change rs1800407, which refers to amino acid causing change Arg419Gln located in exon 13. Single SNP analysis indicated that allele 419Gln is associated with green/hazel iris colour (p < 0.001). According to tree scanning analysis, the proportion of eye colour variation explained by this nucleotide position is merely 4%. Thus, additional variation present in the OCA2 gene and perhaps some other pigment related genes must be taken into account in order to explain the high phenotypic variation in iris colour.

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.

Tumorous variant of scleromyxedema. Successful therapy with intravenous immunoglobulins.

We present an unusual tumorous variety of scleromyxedema mimicking facies leonina in lymphoma. In spite of pronounced and widespread cutaneous changes, hypergammaglobulinaemia and paraproteinaemia, the general condition of the patient was satisfactory, there was no internal involvement and no symptoms of any malignancy. Initially, melphalan and corticosteroids were applied but were not effective. High-dose intravenous immunoglobulin (IVIG) therapy had dramatic effect, and after five 5-day monthly courses the tumours almost regressed and the skin became less hard. After a further five courses in the following year there was complete clearance, which was sustained without any therapy for 1 year (until now). IVIG appears to be the therapy of choice for scleromyxedema. We stress, however, that at the start of therapy, IVIG applications should be supplemented with small doses of melphalan and/or corticosteroids.

[Ulcerative colitis concomitant with pyoderma gangrenosum and erythema nodosum--presentation of two cases]. / Wrzodziejace zapalenie jelit towarzyszace piodermii zgorzelinowej i rumieniowi guzowatemu--pokaz dwóch przypadków.

Authors present case of a 28-year old woman with skin symptoms of pyoderma gangrenosum and ulcerative colitis seriously advanced. The patient benefited from wide resection of the colon and steroid therapy. The other patient was 23-year old woman with ulcerative colitis concomitant with skin changes of erythema nodosum. In this case steroid therapy gave also a very good effect. We tried to find pathogenetic connection between these diseases based on the reports from the medical literature.

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

[Changes in lymphocyte subsets in bronchoalveolar lavage fluid in patients with systemic sclerosis]. / Zmiany w subpopulacjach limfocytów w plynie z plukania oskrzelowo-pecherzykowego u chorych na twardzine ukladowa.

The aim of this study was to estimate if alterations of lymphocyte subsets obtained by broncholaveolar lavage (BAL) were related to clinical data observed in nonsmoking patients with systemic sclerosis (SSc). Clinical examination included chest X-rays, spirometry and arterial blood gasometry. Patients were divided into group A (pulmonary changes present, n = 15) and B (without any changes, n = 7). Healthy subjects constituted the control group (n = 10). BAL lymphocytes were phenotyped using monoclonal antibodies coupling CD4, CD8 (both in coexpression with CD25), CD19 and HLA-DR human antigens and flow cytometer FACStar (Becton-Dickinson). Parallel staining was performed in peripheral blood. BAL lymphocyte typing was completed by BAL routine cytology. In SSc patients we found increased BAL total cell number, percentage of neutrophils, eosinophils and macrophage giant cells, as well as high percent of CD25+ and HLA-DR+ lymphocytes. In the group A neutrophilic alveolitis was observed in nearly half of cases: total lymphocyte number (per 1 ml of BAL fluid) and significantly reduced CD4/CD8 ratio were found. In the group B, as compared with controls, we found significantly elevated lymphocyte total cell number per 1 ml of BAL fluid (including particular subsets: CD3+, CD4+, CD8+). Also significantly high CD4+25+ lymphocyte percent was observed. Summing up, cytological and/or immunological alterations were observed in all examined SSc patients. The intensity of these alterations seems to be related to the clinical data. A decreased value of CD4/CD8 ratio may play a role in the local appearance of pulmonary changes in the course of systemic sclerosis.

[Sarcoidosis--a diagnostic and therapeutic problem]. / Sarkoidoza--problem diagnostyczny i terapeutyczny.

Sarcoidosis is a multi-organ granulomatous disorder of an unknown cause. Skin sarcoidosis occurs in about 20-35% of patients with systemic disease and may also arise in isolation. A wide range of clinical presentations of cutaneous sarcoidosis is recognised. The diagnosis rests on the presence of non-caseating granulomas on skin biopsy. Treatment and overall prognosis of cutaneous sarcoidosis is primarily dependent on the degree of systemic involvement.

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.

Serum levels of soluble TNF alpha receptor type I and the severity of systemic sclerosis.

Several abnormalities of cytokines have been shown to occur in systemic scleroderma; however their correlation with clinical parameters is controversial. Since serum concentrations of cytokine receptors have been shown to correlate with inflammatory processes, including systemic sclerosis, the aim of our study was to compare serum concentrations of TNF alpha receptor type 1 with the concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble interleukin-2 receptor (sIL-2R) and aminoterminal propeptide of procollagen type III (PIII NP). The findings were correlated with the clinical parameters and antibody patterns, and with the disease severity. Serum samples were studied with the use of enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay (RIA) for sTNF alpha R1, sICAM-1, sIL-2R and PIII NP. The series comprised 36 patients with systemic scleroderma: 13 with diffuse variety and 23 with limited variety, and 7 with Raynaud's disease. Healthy volunteers (n = 25) were chosen from doctors and/or other laboratory staff. Increased levels of sTNF alpha-receptor type 1 were found in 77% of patients with diffuse variety and in only 30% of patients with limited form. Increased serum concentrations in patients with diffuse scleroderma and limited variety were found for sICAM-1 54% and 65%, for sIL-2R 46% and 15%, and for PIIINP 77% and 50%, respectively. There were significant correlations between serum levels of sTNF alpha-receptor type 1 and PIIINP (r = 0.653, p < 0.0001), and sTNF alpha-receptor type 1 and sIL-2R (r = 0.625, p < 0.0001), but not between sTNF alpha-receptor type 1 and sICAM-1 (r = 0.127, p < 0.526). Clinical analysis revealed that serum concentrations of sTNF alpha-RI seem to correlate best with the severity of the disease and, as the only parameter, correlated with lung involvement. The study showed that, in addition to recognized parameters of scleroderma severity (IL-2R, PIIINP), a new important marker appears to be sTNF alpha-receptor type 1.

Isolation and amino acid sequence of two trypsin isoinhibitors from duck pancreas.

DPTI II and DPTI IV, two trypsin inhibitors from duck pancreas, have been isolated by affinity chromatography on immobilized anhydrotrypsin, anion exchange and RP-HPLC. The complete amino acid sequence of both inhibitors was determined after reductive carboxymethylation and digestion with Staphylococcus aureus V8 protease or trypsin. The inhibitors were each found to be a single polypeptide chain comprised of 69 amino acid residues and their molecular masses were estimated at 7687 Da for DPTI II and 7668 Da for DPTI IV. The only difference in amino acid sequence between the two inhibitors is the replacement of Arg for His residue in the C-terminal position of DPTI IV.

Peripheral arterial obliterative disease. Cost of illness in France.

The main purpose of this study, carried out in 1995, was to determine, using available sources, the cost of peripheral arterial obliterative disease (PAOD) in France over a 1-year period. This cost-of-illness study was based on a retrospective analysis of the available literature and databases. It involved a description of epidemiological data and a cost estimate of the different medical resources consumed over 1 year. For this latter purpose, a payer perspective was chosen. Data were extracted from national representative surveys and databases with respect to morbidity and mortality [from the National Institute of Health and Medical Research (Institut National de la Santé et de la Recherche Médicale; INSERM) and the National Sickness Insurance Fund for Salaried People (Caisse Nationale d'Assurance Maladie des Travailleurs Salariés; CNAMTS)], consultations, examination tests and drug prescriptions [from the French Medical Audit conducted by Intercontinental Medical Statistics (IMS)], hospitalisations [from the Statistical Unit of the Department of Health-Service des Statistiques, des Etudes et des Systemes d'Information (SESI) and the National Public Research Centre in Health Economics (Centre de Recherche d'Etude et de Documentation en Economie de la Santé; CREDES)] and related health expenditure from CNAMTS. In France, the prevalence of stage II PAOD (Leriche and Fontaine classification) in 1992 was estimated to be 675,000; 53% of these patients had undergone vascular or bypass surgery. The total annual cost of healthcare (including consultations, drugs, laboratory tests, hospitalisation and hydrotherapy) for the management of patients with PAOD ranged from 3.9 billion French francs (F) to F4.6 billion (1995 values), depending on the type of hospital considered. 50% of this cost was related to hospitalisations and 75% was covered by the CNAMTS. Although this study was only a partial evaluation and did not take into account indirect costs or nonmedical direct costs, such as transport and care by healthcare assistants and paramedics, these results may help to establish public health priorities and modify clinical practice to favour an earlier diagnosis of PAOD.

Incremental cost-effectiveness ratio of alteplase in patients with acute myocardial infarction in the French setting.

On the basis of data collected from general hospital centres in France on 704 patients initially presenting with acute myocardial infarction, the mean 1-year cost of treatment was calculated to be 52,160 French francs (F) per patient (1994 values). This was independent of whether the patient received thrombolysis, and included all costs associated with initial hospitalisation including a stay in intensive care, cardiology or medical units, as well as rehospitalisations, revascularisation procedures and any drugs prescribed. When only those patients who survived the initial hospitalisation were considered, the mean cost of treatment was F58,184 per patient. Among patients who received thrombolysis during their initial hospitalisation, the respective mean 1-year costs were F74,684 per patient for those treated with alteplase and F64,866 per patient for those treated with streptokinase (p = 0.09). This nonsignificant difference can be explained by the higher cost of alteplase relative to that of streptokinase, the lower mortality rate associated with alteplase during the initial hospitalisation period (9.2% versus 10.6%) and the difference in the percentage of additional revascularisations required in the 2 treatment groups (32.8% versus 42.3%). Combining the pharmacoeconomic data collected in the French general hospital setting with incremental patient survival data stemming from the Global Utilisation of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial showed that the incremental cost-effectiveness ratio of alteplase versus streptokinase amounted to F70128 per life-year saved for the total group, and F52035 per life-year saved for those patients who survived the initial period of hospitalisation.

Cost saving of 5-day therapy with cefpodoxime proxetil versus standard 10-day beta-lactam therapy for recurrent pharyngotonsillitis in adults. A prospective general practice study.

A prospective economic evaluation was undertaken as part of a randomised clinical trial conducted in French general practice. Its aim was to compare the costs and therapeutic outcomes of a 5-day course of cefpodoxime proxetil 100 mg twice daily with 10-day courses of phenoxymethylpenicillin (penicillin V) 1 MIU 3 times daily and amoxicillin-clavulanic acid 500/125 mg 3 times daily for the treatment of recurrent pharyngotonsillitis in 575 adults. Over the 6-month study period, the total cost to society per patient treated with cefpodoxime proxetil was 123 French francs (FF; 1993 values) lower than that for patients treated with phenoxymethylpenicillin and FF227 lower than that for patients treated with amoxicillin-clavulanic acid. This cost saving was primarily attributable to a lower initial drug acquisition cost, and a reduction in the cost associated with lost productivity and general practitioner consultations. Furthermore, as a consequence of a lower relapse rate, the cost-saving ratio for cefpodoxime proxetil, expressed as FF per month free of recurrence, was FF50 less than for phenoxymethylpenicillin and FF60 less than for amoxicillin-clavulanic acid. Thus, a 5-day course of cefpodoxime proxetil is likely to be less costly for treatment of pharyngotonsillitis in the general practice setting than standard 10-day courses of phenoxymethylpenicillin and amoxicillin-clavulanic acid.

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.