Environmental risk assessment of the anionic surfactant sodium lauryl ether sulphate in site-specific conditions arising from mechanized tunnelling.

Sodium lauryl ether sulphate (SLES) is the anionic surfactant commonly utilized as the main synthetic chemical component in most foaming agents used in mechanized tunnelling. This produces huge amounts of soil debris which can contain residual concentrations of SLES. The absence of environmental quality standards for soil and water and the limited information about SLES persistence in real excavated soils do not facilitate any re-use of soil debris as by-products. The environmental risk assessment (ERA) of foaming agents containing SLES can be a valid tool for this purpose. In this study, an ERA analysis of SLES in 12 commercial formulations (cf) used for tunnelling excavation was performed. Various soils from different tunnel excavation sites were conditioned with the selected foaming agents containing SLES. Predicted or measured environmental concentrations (PECs, MECs) were determined and then compared with the Predicted No Effect Concentrations (PNECs) for both the terrestrial and aquatic compartments. The results indicate a reduction of the potential risk over time for these ecosystems, with differences depending on both the commercial foaming formulation and the spoil material characteristics. However, because potential threats to the natural environment cannot be excluded, some risk management and mitigation actions are discussed.

Transport Properties of Li-TFSI Water-in-Salt Electrolytes.

Water-in-salts are a new family of electrolytes that may allow the development of aqueous Li-ion batteries. They have a structure that is reminiscent of ionic liquids, and they are characterized by a high concentration of ionic species. In this work, we study their transport properties and how they evolve with concentration by using molecular dynamic simulations. We first focus on the choice of the force field. By comparing the simulated viscosities and self-diffusion coefficients with experimental measurements, we select a set of parameters that reproduces well the transport properties. We then use the selected force field to study in detail the variations of the self and collective diffusivities of all the species as well as the transport number of the lithium ion. We show that correlations between ions and water play an important role over the whole concentration range. In the water-in-salt regime, the anions form a percolating network that reduces the cation-anion correlations and leads to rather large values for the transport number compared to other standard electrolytes.

Spatial-temporal analysis and risk characterisation of pesticides in Alpine glacial streams.

We analysed the spatial and temporal distribution of a selection of pesticides in Alpine glaciers used on the Po Plain in Northern Italy, near the Alps. By analysing a 102-m ice core taken from the Lys Glacier (Monte Rosa massif, Italy), we highlight historical contamination from the insecticide chlorpyrifos and the herbicide terbuthylazine, confirming the role of alpine glaciers as temporal sinks. In addition, we collected meltwater samples from six glaciers distributed along the Alpine Arc during the summer of 2016, which showed widespread contamination by pesticides. Overall, chlorpyrifos and terbuthylazine dominated the contaminant fingerprint of all of the studied glaciers, with contamination peaks occurring at the beginning of the melting season. This highlights the importance of the medium-range atmospheric transport of these pesticides in connection with agricultural practices in the areas beneath the Italian Alps, where they are widely applied. The release of pesticides in meltwater can lead to potential risks to the aquatic ecosystems of headwater streams, as we demonstrate for chlorpyrifos. This suggests that the medium-range atmospheric transport of pesticides should be considered as part of regulations to protect the water quality of these pristine environments.

Shaping Ability of ProTaper Next, WaveOne, and Reciproc in Simulated Root Canals.

INTRODUCTION: The study aimed to compare the shaping and preservation of the original curvature of simulated curved root canals using the following instruments: Reciproc (Rcp), WaveOne (Wo), and the ProTaper Next system (Ptn). MATERIALS AND METHODS: A total of 45 resin blocks with simulated curved root canals were divided into three groups (n = 15), prepared using the Rcp (R25), Wo (25/0.8), and Ptn (X2) instruments. Standardized photographs were taken before and after canal instrumentation. After the superimposition of the images, the amount of resin removed from the curvature's inner and outer walls was measured at six apical levels, at intervals of 1 mm. The canals' angles of curvature before and after instrumentation were subtracted. RESULTS: There were no significant differences between the instruments in terms of the total amount of resin removed of the inner or outer walls of the apical curvature (p > 0.05). The Rcp instruments provided the best resin removed ratios between the walls. The means of the change in angle were as follows: Wo = 2.15°, Ptn = 0.92°, and Rcp = 0.21°. WaveOne caused significantly higher deviations than Rcp. CONCLUSION: All of the instruments demonstrated a tendency to straighten the simulated root canal. Instruments that use rotary movement achieved an effect similar to that of the reciprocating instruments in relation to change in angle. CLINICAL SIGNIFICANCE: Deviations from the original shape of the root canal could have a negative impact on the quality of a filling and consequently on the success of the endodontic treatment.

Growth patterns of Italian local chicken populations.

Predictions of growth are important factors that contribute to the profitability of an operation in poultry production. Modern commercial hybrids have a higher body growth in comparison with the local purebreds. However a niche market for meat and egg poultry production needs to be established using local purebreds to promote biodiversity. The aim of this study was to model the growth response of male and female chickens belonging to 5 local Italian populations: a commercial slow-growing hybrid (Berlanda, B), the Padovana pure breed [2 plumage varieties: silver, argentata (PA) and chamois, camosciata (PC)], and their crosses PC×B and PC×PA. A total of 398 one-day-old birds were reared until 180 d of age under indoor conditions. The linear and 3 nonlinear models (logistic, Gompertz, and Richards) were compared to study the growth patterns of these chicken populations. Significant (P < 0.01) differences were observed among the genotypes for several curve parameters. In males, PC×B showed the lowest age at inflection point, B showed the highest age and BW, whereas PA showed the highest age and the lowest weight. In females, the age at the inflection point did not differ among the groups; B showed the highest weight. All the nonlinear models gave a good fit of male and female data with R(2) ranging from 0.992 and 0.999, but the logistic equation had higher value of root mean square error than the Gompertz and the Richards values. Based on residual sum of squares for both sexes, the Richards model was better (P < 0.05) than the logistic but not superior to the Gompertz. The logistic equation showed an overestimation of initial BW for all the groups and sex. For Italian local chicken populations, the Richards model requires a measure of BW recorded at 90 d or after to obtain a good fit of the asymptotic weight. However, the Gompertz model has the advantage that it requires one less parameter than the Richards model.

How much does transgenesis affect wheat allergenicity?: Assessment in two GM lines over-expressing endogenous genes.

Wheat kernel albumins/globulins (A/G) and gluten proteins are responsible for baker's asthma and food allergy in atopic subjects. Although no commercial genetically modified wheats are currently being grown, they are under study and the allergenicity of GM products is a major concern. In order to establish the expected and unexpected effects of genetic transformation on allergenicity and also to carry out a safety assessment of genetic transformation, two GM wheat lines (bread and pasta wheat) transformed with endogenous genes were compared to their untransformed counterparts (wt), first by an allergenomic approach, and second, using ELISA with sera from patients suffering from food allergy to wheat and baker's asthma. The 2D immunoblots performed on sera from patients suffering from food allergy and baker's asthma on the A/G fraction of the four lines (two GM and two wt) revealed comparable IgE-binding profiles. A total of 109 IgE-binding spots were analyzed by mass spectrometry, and most of the proteins identified had already been described as allergens or potential allergens. Only two IgE-binding proteins were specific to one GM line. The concentration of specific IgE against the A/G fractions of GM wheat lines and their wt genotypes differed for some sera. BIOLOGICAL SIGNIFICANCE: The originality of our paper is to relate the transformation of wheat lines with their potential allergenicity using patient sera, such focus has never been done before in wheat and should be of interest to the researches working in this field. Another interesting point of this paper is the study of two types of allergies (respiratory and food) on two wheat genotypes and their GM which reveals that some allergens already known in respiratory allergy could be involved in children suffering from wheat food allergy. In this paper we used a classical 2D proteomic analysis and the protein identifications were performed by mass spectrometry after spot picking and in gel trypsin hydrolysis. Concerning the LC-MS/MS analyses classical software and parameters were used as described in Material and methods. We worked on wheat which is actually not fully sequenced that was a difficulty; we therefore searched against two databanks (proteins and ESTs) in order to compare the results. Moreover all proteins reported in our paper were identified with at least three unique peptides. The identified proteins were checked for their potential allergenicity. In order to have a best interpretation of protein identified in terms of potential allergens, BLAST alignments were performed by using an allergen databank (SDAP). This allows the determination of the cross-reactivity of these identified proteins with known allergens of other species and also the prediction of a potential allergenicity.

Evaluation of an aerosol emitter for mating disruption of Cydia pomonella in Italy.

Some techniques have been developed to disrupt mating (MD) of codling moth (CM) by treating orchards with pheromone. Synthetic pheromone is applied to the crop as a formulation that is designed to protect these generally labile compounds from degradation while gradually releasing pheromone into the atmosphere. In Trentino South Tyrol MD has been adopted successfully (24,500 ha, i.e. 73% of the apple area) to control CM in heavily infested areas; while in areas with low pest pressure, less pesticides are usually applied (2-3 per year) and as a consequence, pheromone mating disruption is not considered economically convenient. Hand applied sealed plastic tubes and plastic ampoules are the two pheromone formulations more widely used. A new pheromone-based control technique, called Puffer, has been recently proposed. Puffers are battery-powered devices that release pheromone from pressurized aerosol cans every 15 minutes for 12 hours or 30 min for 24 hours. During each puff a quantity of 6.95 mg a.i. is emitted. The high release rate of pheromone per puff from aerosol dispensers is thought to compensate for their low application densities (2-2.5 puffer/hectare). Results of three year field trials carried out in Trentino-South Tyrol demonstrated the potential of Puffer as effective tool to control the moth.

Quality of organic eggs of hybrid and Italian breed hens.

The quality of eggs laid by 2 hybrid and 2 Italian dual-purpose genotypes of hens reared under organic farming system was studied. Hens belonging to Hy-Line Brown (brown eggshell, HLB), Hy-Line White (white eggshell, HLW), Ermellinata di Rovigo (brown eggshell, E), and Robusta maculata (brown eggshell, R) genotypes were reared from 24 to 43 wk of age. The trial was carried out from July to December, with environmental temperature ranging from 25°C (±5°C, summer) to 13°C (±7°C, autumn). The HLB eggs were heavier (P < 0.01) than HLW (62.9 vs. 60.4 g), and R eggs were heavier (P < 0.01) than E (56.5 vs. 54.4 g). The albumen weight differed (P < 0.01) among HLB, HLW, R, and E (40.7, 38.3, 32.7, 34.1 g, respectively). The E and R yolk weights were similar (16.2 g) and higher (P < 0.01) than hybrids; HLW yolk was higher (P < 0.05) than HLB (15.8 vs. 15.5 g). The HLB showed the highest (P < 0.01, 6.74 g) shell weight and E had the lowest (P < 0.01; 5.43 g). The yolk cholesterol content was higher (P < 0.01) in the Italian eggs than in the hybrids (258 vs. 219 mg/yolk). The HLB yolk had the lowest (P < 0.01) saturated fatty acids (33.8 vs. 34.9%), and R yolks showed the lowest (P < 0.01) monounsaturated fatty acids (36.3 vs. 38.0%) and the highest (P < 0.01) polyunsaturated fatty acids (28.7 vs. 27.4%) than the other groups. The HLW yolk showed the highest (P < 0.01) n-6/n-3 ratio (13.7) in comparison to the other 3 groups (12.8). During 21 d of storage (at 21°C and 62% RH), the E eggs showed the lowest (P < 0.01) quality (albumen height, 4.93 vs. 5.56 mm; Haugh units, 71 vs. 74). A sensory profile of boiled eggs showed differences (P < 0.05) in odor and flavor sensations and in certain yolk and albumen texture properties according to genotype. The quality of organic eggs from different genotypes differs in relation to the strain but also the interaction with the environmental conditions has to be considered.

Production and characterisation of monoclonal antibodies for the quantification of potentially allergenic xylanase from Aspergillus niger.

Xylanase from Aspergillus niger (ANX) is widely used in bakeries as a processing aid since it stabilises and improves dough quality. An association between allergic symptoms among bakery workers and sensitisation to ANX has been reported, indicating that this enzyme is an occupational allergen. The presence of ANX in dough improvers and semi-finished goods is often hidden due to incomplete and unclear labelling. The quantification of microbial enzymes in these products is necessary and the determination of the actual concentration of ANX in workplaces is therefore essential to assess the occupational risk. To this purpose we have developed and characterised monoclonal antibodies to ANX. The monoclonal antibodies do not show any cross-reaction with other commonly used microbial enzymes, and they allow the detection of ANX in complex mixtures by ELISA inhibition assays down to the concentration limit of approximately 10 µg kg(-1). These mAbs are a valuable tool to detect and quantify ANX and to investigate its allergenic potential in the workplace.

Chemical composition of meat and egg yolk of hybrid and Italian breed hens reared using an organic production system.

A trial was done to study the chemical composition of meat and egg yolk of laying hens belonging to different genotypes reared using an organic production system. Two commercial hybrid hens (Hy-Line Brown and Hy-Line White 36) and 2 Italian dual-purpose breed hens (Ermellinata di Rovigo and Robusta Maculata) were reared from 25 to 44 wk of age. During the experimental period (July to December), the environmental temperature decreased from about 25 to 13 degrees C and the RH increased from 62 to 73%. The photoperiod was 16L:8D. Meat and egg yolks of 44-wk-old hens were analyzed. The Italian breeds showed higher meat production and lower egg production when compared with the hybrids. Genotype affected protein, lipid, and ash content of breast and thigh meat. Hy-Line White and Ermellinata di Rovigo showed the lowest (P<0.01) breast lipid and Hy-Line White had the lowest (P<0.01) thigh lipid. Hy-Line White showed higher (P<0.05) breast and thigh cholesterol. Genotype affected egg yolk cholesterol, which was higher (P<0.01) in Italian breeds than in hybrids. The fatty acid profiles of meat and yolk were significantly affected by genotype. The hybrid and Robusta Maculata meat and egg fatty acid composition may be considered to be more favorable to human health. The results indicate that the ability of laying hens to incorporate fatty acids is genetically dependent and a possible interaction between strain and environmental conditions may exist for the absorption and utilization of dietary components.

Effect of genotype on slaughtering performance and meat physical and sensory characteristics of organic laying hens.

Slaughtering yields and some meat physical and sensorial parameters of laying hens reared under organic system production were studied. The hens belonged to both Italian dual-purpose breeds [Ermellinata di Rovigo (ER; brown eggshell) and Robusta Maculata (RM; brown eggshell)] as well as hybrid genotypes [Hy Line White 36 (white eggshell) and Hy Line Brown (brown eggshell)]. The birds were reared under organic farming system production from 24 to 44 wk of age, when they were slaughtered. They were reared throughout summer and autumn, and the temperature ranged from about 28 to 3 degrees C. Local breeds presented higher (P < 0.01) live BW and dressing percentage compared with hybrids. The RM and ER carcasses had (P < 0.01) the highest breast and leg (thigh and drumstick) percentage, respectively. The muscle-bone ratio of the Hy Line White 36 drumstick was lower (P < 0.05) than the RM ratio, whereas the other groups were intermediate. The ER breast presented the highest (P < 0.01) lightness value and the lowest (P < 0.01) final pH value compared with the other 3 groups. The breast meat significantly differed according to genotype for almost all the studied sensorial parameters (adhesivity, fibrousness, chewiness, solubility, juiciness, tenderness, shear resistance), with the exception of aroma and odor intensity. In the thigh, genotype significantly affected aroma, adhesivity, fibrousness, solubility, tenderness, and shear resistance.

Home and office uroflowmetry for evaluation of LUTS from benign prostatic enlargement.

A group of 107 patients with lower urinary tract symptoms (LUTS) from benign prostatic enlargement (BPE) participated to the HOUSE Study (Home and Office Uroflowmetry Specific Evaluation). Patients received routine investigation, consisting of medical history taking, physical examination including digital rectal examination, prostate-specific antigen (PSA), assessment of symptoms listed both on the International Prostate Symptom Score and on ICS-male questionnaire. We examined the results of uroflowmetry evaluation in this population; data were analysed to observe if any circadian changes of parameters obtained with home uroflowmetry could be detected. We searched a correlation between Q(max), Q(ave) and ICS-benign prostatic hyperplasia symptom score: a significantly inverse correlation was found only for Q(max), confirming Q(max) as a reliable parameter to quantify subjective symptoms. When examining the multiple flow curves recorded in the same patient with home uroflowmetry, voided volume and flow time had usually higher values during night-time: the existence of circadian changes of uroflowmetry parameters in patients with LUTS from BPE was confirmed, and lower values of average and maximum flow rates during sleep hours were recorded in the same patient. In conclusion, when evaluating the natural history or treatment outcome of individual patients or group of patients in clinical trials for evaluation of BPE and LUTS, an assessment including multiple measurements may be useful and of value.

A comparison of the efficacy and tolerability of tamsulosin and finasteride in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

In this multicentre, double-blind study, patients with LUTS/BPH were randomised to 26 weeks with finasteride 5 mg once daily (n=204) or tamsulosin 0.4 mg once daily (n=199). Double-blind treatment was continued for another 26 weeks (total treatment duration: 1 y). The primary efficacy parameter was the difference in mean change in total Symptom Problem Index (SPI) from baseline to end point at week-26 in the intention-to-treat (ITT) and per protocol (PP) populations. Tamsulosin induced a greater improvement in total SPI (-5.2 points or -37%) compared to finasteride (-4.5 points or -31%) at week-26 (P=0.055 in ITT and P=0.032 in PP). Tamsulosin improved urinary symptoms (particularly the more bothersome storage symptoms) and flow more quickly than finasteride. The difference was statistically significant for the SPI from week-1 (reduction, respectively, -2.5 vs -1.8 points, P=0.043) to week-18 and for Qmax from week-1 (increase, respectively, 2.3 vs 0.7 ml/s, P=0.0007) to week-12. Both treatments were well tolerated with a comparable incidence of adverse events, including urinary retention.

Interleukin-6 and glucocorticoids synergistically induce human immunodeficiency virus type-1 expression in chronically infected U1 cells by a long terminal repeat independent post-transcriptional mechanism.

BACKGROUND: Glucocorticoids (GC) such as dexamethasone (Dex) can directly upregulate human immunodeficiency virus type-1 (HIV-1) replication in acutely infected cells and potentiate HIV expression from chronically infected promonocytic U1 cells stimulated with tumor necrosis factor-alpha (TNF-alpha). We have here investigated the potential effect of Dex in U1 cells stimulated with interleukin-6 (IL-6), a cytokine inducing virus expression by acting mostly at a post-transcriptional level on the virus life cycle. MATERIALS AND METHODS: Virus production in culture supernatants was evaluated by reverse transcriptase (RT) activity. GC receptor expression was tested by both binding of [3H]-Dexamethasone 21-mesylate and Northern blotting. Cell-associated HIV protein expression was analyzed by Western blotting, whereas both HIV and monocyte chemoattractant protein-1 (MCP-1) RNA accumulation were evaluated by Northern blotting. HIV transcription was tested by long terminal repeat (LTR) chloramphenicol acetyl transferase (CAT) assay after transient transfection of U1 or U937 cells. Formation of activating protein-1 (AP-1) DNA binding complex in nuclear cell extracts was visualized by electrophoretic mobility shift assay (EMSA), whereas ERK1/2 mitogen-activated protein kinase (MAPK) phosphorylation was studied by Western blotting. RESULTS: IL-6 and Dex synergistically induced HIV expression in U1 cells, and this effect was blocked by RU 486. No substantial HIV RNA accumulation was demonstrated in U1 cells co-stimulated with IL-6 and Dex, whereas IL-6 upregulated the expression of MCP-1 RNA, and this effect was inhibited by Dex. In contrast, Dex potentiated IL-6 induced activation of AP-1 and ERK1/2 MAPK phosphorylation, as revealed by EMSA. HIV-1 LTR driven transcription was observed in U1 cells stimulated with TNF-alpha and this effect was potentiated by Dex. In sharp contrast, no induction of LTR-directed CAT activity was observed in transfected U1 cells (or in their parental uninfected U937 cells) stimulated with IL-6 and Dex either alone or in combination. CONCLUSIONS: High levels of virion production can be induced in latently infected cells by stimulation with IL-6 and Dex in the absence of activation of the HIV LTR or viral transcription in spite of activation of both ERK1/2 MAPK and AP-1. These findings suggest the existence of LTR-independent pathways influenced by cytokine and GC through which HIV can maintain substantial levels of protein expression and virion production.

Aims and methods. LUTS suggestive of BPH.

OBJECTIVE: Few epidemiological studies are available on Italian patients with lower urinary tract symptoms and their QoL. QUIBUS (QUality of life Investigated in BPH patients with Urinary Symptoms) is an observational longitudinal study aimed at evaluating symptoms and QoL in a large sample of Italian patients and investigating their correlation with demographic, social and clinical characteristics of BPH. PATIENTS AND METHODS: Patients with lower urinary tract symptoms and prostate enlargement suggestive of BPH (both old and new diagnosis) were enrolled between November 1998 and May 1999 in 31 Italian centers of urology. This longitudinal investigation consists of an enrollment visit, in which demographic, social and clinical aspects are recorded as baseline data, and a follow-up visit after 1 year of treatment freely assigned by the investigators. Symptoms and QoL are assessed by means of IPSS, ICS-BPH (at both visits) and SF-36 (only at the follow-up visit) questionnaires. RESULTS: 1,033 patients were enrolled. The follow-up visit is still under evaluation. In this series of papers the baseline results are presented and discussed in terms of (i) medical management, (ii) life-style, (iii) symptoms, bothersomeness and QoL, (iv) sexual function of a large and representative sample of Italian patients and (v) uroflowmetry.

Characteristics and use as spin trapping agent of a beta-phosphorylated nitroso compound, DEPNP.

2-(Diethylphosphonate)-nitrosopropane (DEPNP), prepared by oxidation of the corresponding aminophosphonate, was found to essentially exist as monomer in both water and organic solvents. The mechanisms of its degradation under 80 degrees C heating or visible light exposure were studied by EPR spectroscopy: its decomposition gave rise to paramagnetic by-products, which have been identified as DEPNP/.C(CH(3) )(2) [P(O)(OC(2) H(5) )(2) ] and DEPNP/.P(O)(OC(2) H(5) )(2) spin adducts. Despite this drawback, DEPNP was successfully used as spin trapping agents to scavenge various carbon - and phosphorus-centred free radicals both in aqueous and organic media, giving rise to intense EPR spectra characteristic of the species trapped.

Cathepsin B activity regulation. Heparin-like glycosaminogylcans protect human cathepsin B from alkaline pH-induced inactivation.

It has been shown that lysosomal cysteine proteinases, specially cathepsin B, has been implicated in a variety of diseases involving tissue remodeling states, such as inflammation, parasite infection, and tumor metastasis, by degradation of extracellular matrix components. Recently, we have shown that heparin and heparan sulfate bind to papain specifically; this interaction induces an increase of its alpha-helix content and stabilizes the enzyme structure even at alkaline pH (Almeida, P. C., Nantes, I. L., Rizzi, C. C. A., Júdice, W. A. S., Chagas, J. R., Juliano, L., Nader, H. B., and Tersariol, I. L. S. (1999) J. Biol. Chem. 274, 30433-30438). In the present work, a combination of circular dichroism analysis, affinity chromatography, cathepsin B mutants, and fluorogenic substrate assays were used to characterize the interaction of human cathepsin B with glycosaminoglycans. The nature of the cathepsin B-glycosaminoglycans interaction was sensitive to the charge and type of polysaccharide. Like papain, heparin and heparan sulfate bind cathepsin B specifically, and this interaction reduces the loss of cathepsin B alpha-helix content at alkaline pH. Our data show that the coupling of cathepsin B with heparin or heparan sulfate can potentiate the endopeptidase activity of the cathepsin B, increasing 5-fold the half-life (t(12)) of the enzyme at alkaline pH. Most of these effects are related to the interaction of heparin and heparan sulfate with His(111) residue of the cathepsin B occluding loop. These results strongly suggest that heparan sulfate may be an important binding site for cathepsin B at cell surface, reporting a novel physiological role for heparan sulfate proteoglycans.

Ala scan analogues of HOE 140. Synthesis and biological activities.

The role of the amino acids contained in the sequence of HOE 140 (H-DArg(1)-Arg(2)-Pro(3)-Hyp(4)-Gly(5)-Thi(6)-Ser(7)-DTic(8)-Oic(9 )-Arg(10)-OH), a potent and selective bradykinin B(2) receptor peptide antagonist, has been investigated by the replacement of each original residue (one by one) with Ala. The resulting set of decapeptides has been tested for the B(2) antagonist activity as well as for competition with the binding of [3H]BK to plasma membranes of the human umbilical vein (hUV). Positive correlations have been established between data obtained with the bioassay and with the binding in the hUV (same species, same tissue) and also between the two bioassays, the guinea-pig ileum (GPI) and the hUV (different species, different tissue). The structure-activity study has shown that the replacement of any of the residues that constitute HOE 140 with Ala is accompanied by a decrease of potency of at least 1 log unit. The analogues can be divided into three groups, with Ala(1) and Ala(7) showing affinities lower than HOE 140 by a factor of 10, Ala(4) and Ala(10) by a factor of 100 and Ala(2), Ala(5), Ala(6), Ala(8) and Ala(9) by a factor higher than 100 (100-1000). To verify the effect of chirality, the DAla(5) and DSer(7) analogues were synthesized and it was found that the substitution with a D-residue in position 5 is not tolerated while that in position 7 is favourable. The DSer(7) derivative is the most potent analogue found in this study: it shows potency as high as that of HOE 140 in the bioassays.

Characterization of FR 172357, a new non-peptide bradykinin B(2) receptor antagonist, in human, pig and rabbit preparations.

FR 172357, a new non-peptide antagonist of the kinin B(2) receptor was tested in three isolated vessels, the human umbilical vein, the rabbit jugular vein, and the pig coronary artery, to evaluate its antagonistic activities against bradykinin. FR 172357 displaced to the right the concentration-response curves of bradykinin. The displacements were parallel to the controls without reduction of the maximum effect in the human umbilical vein and in the rabbit jugular vein, but not in the pig coronary artery. Schild plots confirmed that FR 172357 acts as a competitive antagonist in the human umbilical vein (pA(2) 8.65) and in the rabbit jugular vein (pA(2) 9. 07), and as a non-competitive antagonist in the pig coronary artery (pK(B) 10.14). FR 172357 is selective for the kinin B(2) receptor since it does not influence the effects of Lys-des-Arg(9)-bradykinin in the human umbilical vein, in the rabbit aorta, and in the pig renal vein. It is specific because it does not affect the contractions induced by angiotensin II, noradrenaline, 5-hydroxytryptamine, or endothelin-1 in the human umbilical vein. It, however, interacts with the tachykinin NK(1) receptor of the rabbit jugular vein and pig coronary artery. Compared to other bradykinin B(2) receptor antagonists, FR 172357 emerges as a very potent compound, which may represent a choice for experimental (and clinical?) applications.