Nature based solutions to mitigate soil sealing in urban areas: Results from a 4-year study comparing permeable, porous, and impermeable pavements.

Soil sealing is one of the most pervasive forms of soil degradation that follows urbanization and, despite innovative pavements (i.e. pervious) are being installed in urban areas to mitigate it, there is little research on the effects of pervious pavements on soil water and carbon cycle and on the physiology of urban trees. The aim of this 4-year experiment was to assess the effects of three pavements, differing in permeability to water and gases, on some soil physical parameters, and on growth and physiology of newly planted Celtis australis and Fraxinus ornus. Treatments were: 1) impermeable pavement (asphalt on concrete sub-base); 2) permeable pavement (pavers on crushed rock sub-base); 3) porous design (porous pavement on crushed rock sub-base); 4) control (unpaved soil, kept free of weed by chemical control). Soil (temperature, moisture, oxygen content and CO2 efflux) and plant (above- and below-ground growth, leaf gas exchange, chlorophyll fluorescence, water relations) parameters were measured. All types of pavements altered the water cycle compared to unpaved soil plots, but this disturbance was less intense in porous pavements than in other soil cover types. Porous pavements allowed both higher infiltration and evaporation of water than both pavers and asphalt. Reduction of evaporative cooling from soil paved with permeable and impermeable pavements contributed to significant soil warming: at 20cm depth, soils under concrete pavers and asphalt were 4 and 5°C warmer than soil covered by porous pavements and unpaved soils, respectively. Thus, enhancing evaporation from paved soil by the use of porous pavements may contribute to mitigating urban heat islands. CO2 greatly accumulated under impermeable and permeable pavements, but not under porous pavements, which showed CO2 efflux rates similar to control. Soil oxygen slightly decreased only beneath asphalt. Growth of newly planted C. australis and F. ornus was little affected by pavement type. Tree transpiration rapidly depleted soil moisture compared to the not-planted scenario, but soil moisture did not fall below wilting point (particularly in the deeper soil layers, i.e. 40-50cm) in any treatment. While C. australis showed similar leaf gas exchange and water relations in all treatments, F. ornus showed a depression in CO2 assimilation and slight signs of stress of the photosynthetic apparatus when planted in soil covered with impermeable pavement. The effects of soil cover with different materials on tree growth and physiology were little, because newly planted trees have most of their roots still confined in the unpaved planting pit. Still, the reduction of soil sealing around the planting pit triggered the establishment of sensitive species such as ash. Further research is needed to assess the effects of different pavement types on established, larger trees.

4He dose- and track-averaged linear energy transfer: Monte Carlo algorithms and experimental verification.

Objective.In the present hadrontherapy scenario, there is a growing interest in exploring the capabilities of different ion species other than protons and carbons. The possibility of using different ions paves the way for new radiotherapy approaches, such as the multi-ions treatment, where radiation could vary according to target volume, shape, depth and histologic characteristics of the tumor. For these reasons, in this paper, the study and understanding of biological-relevant quantities was extended for the case of4He ion.Approach.Geant4 Monte Carlo based algorithms for dose- and track-averaged LET (Linear Energy Transfer) calculations, were validated for4He ions and for the case of a mixed field characterised by the presence of secondary ions from both target and projectile fragmentation. The simulated dose and track averaged LETs were compared with the corresponding dose and frequency mean values of the lineal energy,yD¯andy¯F, derived from experimental microdosimetric spectra. Two microdosimetric experimental campaigns were carried out at the Italian eye proton therapy facility of the Laboratori Nazionali del Sud of Istituto Nazionale di Fisica Nucleare (INFN-LNS, Catania, I) using two different microdosimeters: the MicroPlus probe and the nano-TEPC (Tissue Equivalent Proportional Counter).Main results.A good agreement ofL¯dTotalandL¯tTotalwithy¯Dandy¯Texperimentally measured with both microdosimetric detectors MicroPlus and nano-TEPC in two configurations: full energy and modulated4He ion beam, was found.Significance.The results of this study certify the use of a very effective tool for the precise calculation of LET, given by a Monte Carlo approach which has the advantage of allowing detailed simulation and tracking of nuclear interactions, even in complex clinical scenarios.

Air pollution deposition on a roadside vegetation barrier in a Mediterranean environment: Combined effect of evergreen shrub species and planting density.

Leaf deposition of PM10-100, PM2.5-10, PM0.2-2.5 and of 21 elements was investigated in a roadside vegetation barrier formed by i) two evergreen shrub species (Photinia × fraseri, Viburnum lucidum), with ii) two planting densities (0.5, 1.0 plant m-2), at iii) three distances from the road (2.0, 5.5, 9.0 m), at iv) two heights from the ground (1.5, 3.0 m), and on v) three dates (Aug, Sep, Oct). The presence of black and brown on-leaf PM10-100 and their element composition were detected by microscopy and image analysis. Pollutant deposition was also measured using passive samplers at five distances from the road (2.0, 5.5, 9.0, 12.5, 19.5 m) in the area of the barrier and in an adjacent lawn area. V. lucidum had more PM2.5-10 and PM0.2-2.5 on leaves than P. × fraseri, while most elements were higher in P. × fraseri. Most pollutants decreased at increasing distances from the road and were higher at 1.5 m from the ground compared to 3.0 m. Higher planting density in P. × fraseri enhanced the deposition of PM10-100 and PM2.5-10, while in V. lucidum, the planting density did not affect the depositions. Black PM10-100 decreased a long distance from the road and was entirely composed of carbon and oxygen, which was thus identified as black carbon from fuel combustion. The vegetation barrier had a higher deposition of most PM fractions at 5.5-12.5 m, while in the lawn area, depositions did not change. At 19.5 m, the PM10-100 was 32% lower behind the barrier than in the lawn area. In conclusion, the vegetation barrier changed the deposition dynamics of pollutants compared to the lawn area. These results strengthen the role of vegetation barriers and shrub species against air pollution and may offer interesting insights for the use of new road green infrastructures to improve air quality.

Enhancement of oleyl alcohol anti tumor activity through complexation in polyvinylalcohol amphiphilic derivatives.

Oleyl alcohol was complexed with new amphiphilic polyvinylalcohol derivatives with the aim of increasing its aqueous solubility, thus improving bioavailability and favoring its antitumor activity. Water-soluble amphiphilic polymers were prepared by polyvinyl alcohol (PVA) substitution with oleyl chains through a succinyl spacer at 2% and 3% substitution degree. The complexes were obtained by spray-drying hydroalcoholic solutions of the substituted polymers and free oleyl alcohol at different weight ratios (3:1; 5:1; 10:1 w/w). The main physicochemical characteristics of the complexes were analyzed and correlated to the cytotoxic activity of oleyl alcohol toward tumor cell lines. The complexes strongly increased the aqueous solubility of oleyl alcohol and provided oleyl alcohol release in the presence of extractive conditions (simulating in vivo absorption). The complexes obtained by 10:1 polymer:fatty alcohol weight ratio offered higher release rates than the 5:1 and 3:1 ratios, respectively. Complexation also increased oleyl alcohol cytotoxicity toward tumor cells due to increased availability of the active molecule in the aqueous phase. Pure polymers were found to be biocompatible and no toxic effect was detected up to the highest concentration used in the present study (500 mu g/ml). The complexation of oleyl alcohol with the polymers analyzed here efficiently increased the availability of the fatty alcohol in aqueous environment. The enhanced cytotoxicity toward tumor cells of the complexed oleyl alcohol and the polymer biocompatibility make these amphiphilic PVA derivatives interesting candidates for soluble pharmaceutical formulations containing hydrophobic drugs whose therapeutic potential is often underestimated due to unsuitable levels of their aqueous solubilization.

Switching to anastrozole versus continued tamoxifen treatment of early breast cancer. Updated results of the Italian tamoxifen anastrozole (ITA) trial.

BACKGROUND: Tamoxifen, for many years the 'gold standard' in the adjuvant setting for the management of endocrine sensitive early breast cancer, is associated with an increased risk of endometrial cancer and other life-threatening events. Moreover, many women relapse during or after tamoxifen therapy due to the development of resistance. This provided the rationale for a switching trial with anastrozole, the updated results of which are reported here. PATIENTS AND METHODS: This trial investigated the efficacy of switching to anastrozole for women already receiving tamoxifen. After 2-3 years of tamoxifen treatment, postmenopausal, node-positive, ER-positive patients were randomized to receive either anastrozole 1 mg/day or to continue tamoxifen, 20 mg/day, giving a total duration of 5-years treatment. The primary end point was disease-free survival and secondary endpoints were event-free survival, overall survival and safety. RESULTS: A total of 448 patients were enrolled. At a median follow-up time of 64 months (range 12-93), 63 events had been reported in the tamoxifen group compared with 39 in the anastrozole group [HR 0.57 (95% CI 0.38-0.85) P = 0.005]. Relapse-free and overall survival were also longer in the anastrozole group [HR 0.56 (95% CI 0.35-0.89) P = 0.01 and 0.56 (95% CI 0.28-1.15) P = 0.1]. However, the latter difference was not statistically significant. Overall more patients in the anastrozole group experienced at least one adverse event (209 versus 151: P = 0.000). However, numbers of patients experiencing serious adverse events were comparable (37 versus 40, respectively: P = 0.7). CONCLUSIONS: Switching to anastrozole after the first 2-3 years of treatment was confirmed to improve event-free and relapse-free survival of postmenopausal, node-positive, ER-positive early breast cancer patients already receiving adjuvant tamoxifen.

Thermodynamic features of bile salt-human serum albumin interaction.

Interaction with human serum albumin is responsible for important aspects of the physiological behaviour of bile salts, although this factor has not been adequately examined. The nature of the binding is investigated here by means of thermodynamic parameters determined by equilibrium dialysis and microcalorimetric measurements. The positive enthalpy and entropy values obtained indicate the presence of a poorly specific hydrophobic bonding.

Modified polyvinylalcohol for encapsulation of all-trans-retinoic acid in polymeric micelles.

All-trans-retinoic acid (ATRA) is now included in many antitumor therapeutic schemes for the treatment of acute promyelocytic leukaemia, Kaposi's sarcoma, head and neck squamous cell carcinoma, ovarian carcinoma, bladder cancer and neuroblastoma. Unfortunately its poor aqueous solubility hampers its parenteral formulation. To date, there is no parenteral formulation of ATRA commercially available and oral administration of ATRA is associated with progressively diminishing ATRA levels in plasma, which is related to induction of retinoic acid-binding protein and increased drug catabolism by cytochrome P-450-mediated reaction. An ATRA formulation, obtained by complexation of the drug into polymeric micelles, might be suitable for parenteral administration overcoming these unwanted effects. To this purpose we prepared an amphiphilic polymer by polyvinylalcohol (PVA) substitution with oleyl amine at 1.5% substitution degree (mol substituent per 100 mol hydroxyvinylmonomer) and evaluated its functional properties with regard to ATRA complexation. The substituted polymer displayed ability to interact with ATRA both in aqueous solution and in the solid state following spray-drying of drug-polymer hydro-alcoholic solutions. The spray-dried complexes rapidly dissolved in water providing high levels of ATRA solubilization as a function of the drug-polymer weight ratio. The complexes characterized by 1:5 drug-polymer weight ratio provided higher levels of ATRA solubilization than 1:3 and 1:10 drug-polymer weight ratios respectively. Pre-formed polymeric micelles in water equilibrated in the presence of excess solid ATRA provided the lowest levels of solubilization. The drug release from the complexes was very slow in PBS, indicating their suitability in antitumor drug targeting where a fundamental requirement is stability towards drug release for at least 24 h, corresponding to the average circulation time period of macromolecular carriers. The cytotoxicity studies against neuroblastoma cell lines outlined increased cytotoxicity of complexed ATRA with respect to free ATRA, likely due to the increased bioavailability of the hydrophobic drug from the complex. We conclude that ATRA entrapped into self-assembling polymer micelles may be a useful parenteral ATRA formulation overcoming the unwanted pharmacological mechanism that lead to acquired retinoid resistance.

A factor analysis for complex systems containing nimesulide.

Binary systems containing Nimesulide and PEG 4000 were prepared by the melting method in the concentration range 3-25% w/w of the drug. The systems are homogeneous in the molten state, while, after cooling, two phases were formed of different density. They were manually separated and separately studied. Upper phases are richer in PEG 4000, while the lower ones contain the drug at levels even higher than those of the starting mixtures. The two phases were examined by DSC and UV techniques; high dissolution rates were observed with upper phases, while lower phases did not display improvement with respect to a physical mixture or micronized drug. With the aim to avoid phase separation, a third component was added to the binary system containing 5% w/w drug, during the melting. The ternary systems were prepared containing sodium dodecyl sulfate, triethanolamine, polysorbate 80, poloxamer, and cetomacrogol: a homogeneous phase was obtained only in two cases (with the addition of sodium dodecyl sulfate and triethanolamine), but only in the presence of triethanolamine dissolution rate was improved. Finally, a factor analysis was performed for complex systems containing a combination of the four additives, each one at two concentrations (1.25 and 2.5% w/w), to evaluate the optimum system in terms of both kinetic and composition parameters. Results suggest that additives affect mainly the physical aspect of the formulation rather than the kinetic behavior, which appears little improved only in a few cases.

Modified doxorubicin for improved encapsulation in PVA polymeric micelles.

Polyvinylalcohol, partially substituted with lipophilic acyl chains, generates polymeric micelles in aqueous phase, containing a hydrophobic core able to encapsulate lipophilic drugs. Two types of polymers were obtained by conjugation of polyvinylalcohol with oleoyl or linoleoyl chains as pendant groups. The polymers, at a substitution degree of approximately 1%, are soluble in water and form polymeric micelles whose size increases with polymer concentration. Doxorubicin was hydrophobized, by linking an oleoyl chain via amide bond, to make the drug more similar to the substituted polymers and promote its encapsulation into the inner core of the micelles. The properties of the drug-polymer systems were evaluated in solution by dynamic light scattering technique and correlated to the physicochemical characteristics of the drug and the substituted polymers. Solubilization tests revealed that the similarity of the chain, in both the polymer and the drug, promotes better drug encapsulation in the oleoyl than linoleoyl derivative. The drug-polymer systems are stable in phosphate buffer saline (pH 7.4) at 37 degrees C, and the release of the drug is activated by the presence of the proteolytic enzyme pronase-E. The enzyme activated drug release and the size of the polymeric micelles, compatible with the pore dimensions of the tumor vessels, make these systems interesting for targeting lipophilic drugs to solid tumors, where the proteolytic enzyme concentration strongly raises with respect to the other body compartments.

Bile acids with cyclopropane-containing side chain. 2. Synthesis and properties of 3 alpha,7 beta-dihydroxy-22,23-methylene-5 beta-cholan-24-oic acid (2-sulfoethyl)amide.

The preparation of 3 alpha,7 beta-dihydroxy-22,23-methylene-5 beta-cholan-24-oic acid (2-sulfoethyl)amide (5) by the one-step EEDQ-induced conjugation between ursodeoxycholic acid "cyclopropylog" (4) and taurine is described. The presence of a cyclopropyl ring adjacent to the amide bond is shown to make it resistant to degradation by intestinal bacteria. This new cyclopropylog is neither deconjugated at the C-24 amide bond nor 7-dehydroxylated when incubated with human stools in anaerobic conditions.

Bile acids with a cyclopropyl-containing side chain. 1. Preparation and properties of 3 alpha, 7 beta-dihydroxy-22,23-methylene-5 beta-cholan-24-oic acid.

3 alpha, 7 beta-Dihydroxy-22, 23-methylene-5 beta-cholan-24-oic acid (5), a side-chain cyclopropyl analogue of ursodeoxycholic acid (1b), has been prepared by the cyclopropanation of 3 alpha, 7 beta-diacetoxy-24-nor-5 beta-chol-22-ene (2) with ethyl diazoacetate , followed by saponification of the resulting cyclopropyl ester (3). The new bile acid presents similar properties to 1b in water. The sodium salt self-aggregates to form micelles at a concentration of 15.5 mM. The cyclopropane ring does not modify the pKa with respect to compound 1b. Cyclopropyl acid 5 is taken up efficiently by rat liver and promptly secreted into bile. It is partially (70%) conjugated with taurine. The bile flow and bile acids and phospholipids secretion are stimulated by 5, while the cholesterol secretion is stimulated by 5 to a lesser extent.

Myocardial perfusion, glucose utilization and oxidative metabolism in a patient with left bundle branch block, prior myocardial infarction and diabetes.

A diabetic patient affected by insulin-dependent diabetes, significant stenosis of left anterior descending (LAD) coronary, thrombolyzed myocardial infarction and complete left bundle branch block (LBBB) was examined by PET. Myocardial perfusion, glucose utilization and oxidative metabolism were evaluated by 13N-ammonia, 18F-fluorodeoxyglucose (FDG) and 11C-acetate, respectively. Despite severe damage in 18F-FDG uptake in the septum, with a septum-to-lateral ratio (S/L R) equal to 0.38, the oxidative metabolism in this area, evaluated quantitatively by dynamic acquisition, was relatively preserved (S/L R = 0.82), with a distribution similar to perfusion (S/L R = 0.87). These data reveal selective damage in glucose utilization in the septum in LBBB, unrelated to perfusion reduction and with preserved oxidative metabolism. Moreover, our experience could suggest an overestimation of the necrotic area by 18F-FDG in LBBB patients.

Retained gastric antrum syndrome diagnosed by [99mTc] pertechnetate scintiphotography in man: hormonal and radioisotopic study of two cases.

Retained-antrum syndrome is a rare condition, occurring in Billroth II gastrectomised patients, in which an ulcer recurs associated with high levels of circulating gastrin. Some gastrin tests are useful to differentiate a retained antrum from a gastrinoma, but a firm diagnosis is sometimes very difficult. We have studied two cases of retained-antrum syndrome both by gastrin tests and by [99mTc] pertechnetate scintiphotography. By this method a prominent area of activity was observed on the anatomic site of the duodenal stump bottom. It appeared after 20 or 30 min and lasted for the 2 hr of observation. After surgical resection, no area of activity was observed at the scintiphotographic followup. No false positive was observed out of the more than 30 subjects studied. Scintiphotography by pertechnetate seems able to demonstrate the presence and the size of retained gastric antrum in B II gastrectomised patients with recurrent ulcer.

Cancer in a young population in a dioxin-contaminated area.

An industrial accident in Seveso, Italy, in 1976, caused contamination of the residential community with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We investigated cancer occurrence in the first post-accident decade (1977-1986) among nearly 20,000 subjects aged 0-19 years. People who left the area were actively followed with a 99% follow-up rate. For reported cancer cases confirmation was obtained through consultation with original medical records. Two ovarian cancers were observed versus none expected. A suggestive increase was seen for Hodgkin's lymphoma (relative risk [RR] = 2.0; 95% confidence interval [CI] = 0.5-7.6). Myeloid leukaemia showed a clear, but not statistically significant increase (RR = 2.7; 95% CI = 0.7-11.4). The most prominent result concerned thyroid cancer, not just for the magnitude of the increase (two cases, RR = 4.6; 95% CI = 0.6-32.7), but also for its consistency with experimental findings and previous observations in humans. Any conclusive interpretation would be premature because of the short time since initial exposure, ecological definition of exposure status, and limited number of events.

Percolation thresholds in ultrasound compacted tablets.

Twenty matrix systems with different KCl content (as drug model, from 10 to 90% w/w) and Eudragit RS-PM (as inert excipient) were prepared using an ultrasound-assisted press and a traditional eccentric machine. The release behavior from both types of matrices was examined; the kinetic parameters for the release (intrinsic dissolution) and the technological properties of the final tablets (total porosity) were used to estimate the percolation threshold for the drug model and the excipient in both systems. For the systems compacted by ultrasound (US) the estimated value for the excipient percolation threshold ranges from 13.4 to 20.2% v/v (lower than that found for traditional tablets), that agrees with a continuum percolation model suggesting the presence of a continuum phase inside the tablet. This depends on a thermoplastic deformation of Eudragit RS-PM under ultrasound, that destroyed the particulate system of the excipient and transform it into a continuum medium. The percolation threshold for KCl ranged from 58.6 to 61.0% v/v for US and from 26.7 to 42.2% v/v for the traditional tablets. The higher value for ultrasound compacted tablets can be explained by the difficulty of KCl to outcome from a matrix containing insoluble phase that surrounds KCl crystals.

Antimicrobial activity of basic cholane derivatives. X. Synthesis of 3 alpha- and 3 beta-amino-5 beta-cholan-24-oic acids.

A simple and convenient route to 3 alpha- and 3 beta-amino-5 beta-cholan-24-oic acids was developed via Leuckart-Wallach amination reduction and subsequent acid hydrolysis. Two epimeric formylamino derivatives were produced (alpha and beta), approximately in a 1:1 ratio, as determined by 13C nuclear magnetic resonance spectroscopy. The two isomers were separated by making use of their different solubilities in ethyl ether. The absolute configuration of the two amino acids was assigned by comparison with authentic reference samples.

Tissue polypeptide antigen (TPA) modifications in hepatic cirrhosis, aggressive chronic hepatitis, persistent chronic hepatitis, and in minimal pathology.

A total of 104 patients with various liver diseases were studied. Hepatic biopsy was performed and the AST, ALT and TPA in serum were measured. Higher levels of TPA, AST and ALT were found in CAH and LC, lower in CPH and MHP. High serum TPA values, usually suggesting the possibility of neoplasm, should be considered with attention. A follow-up with periodic TPA assays (in addition to AST and ALT) is suggested in patients with acute hepatitis, in order to predict further possible complications such as CAH and LC.

Serum thymidine kinase (TK) evaluation in HIV infection.

Serum thymidine kinase (TK), measured using Prolifigen TK-REA, from AB Sangtec Medical, was investigated in 24 HIV seropositive patients without immunological alterations, 26 seropositives with immunological alterations, 125 LAS, 25 ARC, and 20 AIDS. Subjects with serological markers of prior EBV, HBV, and CMV infection were included but none with acute infectious mononucleosis or acute viral hepatitis. Serum TK was elevated from the beginning of the HIV infection, the seropositive stage, and more markedly afterwards during the course of the infection, with a close correlation with the stage. TK also increased during AZT treatment, due to bone-marrow toxicity. On lowering the dosage or discontinuing the drug TK returned to basal levels. Although the rise in serum may well not be correlated only with the HIV infection, it does add to the picture given by other clinical and/or laboratory methods. Serum TK can be a helpful laboratory test in the follow-up of patients with HIV infection, especially when serum levels are disproportionate to the stage, opportunistic infections, lymphoproliferative malignancies. In such cases bone-marrow toxicity due to treatment can be suspected.

Interaction of iron(II) with bile salts.

Iron(II) ions react with small aggregates of cholate, glycocholate, chenodeoxycholate, and deoxycholate to form soluble and colloidal compounds. Taurocholate under conditions used does not react with the Fe2+ ion. Small aggregates of dihydroxy bile salts (predominating in the premicellar region, at concentrations of the bile salt above 1 mmol dm-3) have a larger affinity for Fe2+ compared to those formed from cholate anions. In their interactions with small aggregates of cholate anions, the Fe2+ ion shows an affinity comparable to that of Cu2+ and Cd2+ and somewhat larger than that of Zn2+. Small aggregates of cholate show a higher ability to mask Fe2+ than those of taurocholate and glycocholate. Interaction of glycocholic acid anions with Fe2+ ions is sufficient to prevent iron(II) precipitation.

Interaction between Cu2+ ions and cholic acid derivatives followed by polarography.

Interaction of bile salts with Cu2+ ions in unbuffered systems containing 0.15 M NaNO3 was followed by measuring polarographic limiting currents and half-wave potentials. Whereas taurocholate forms neither soluble complexes nor compounds of limited solubility, cholate, glycocholate, and dehydrocholate from both soluble complexes and slightly soluble salts of copper(II) with small aggregates of bile salts. The stability of soluble complexes is comparable for cholates, dehydrocholates, acetates, and acetylglycinates, but smaller for glycocholates. The solubility of the copper(II) salts with small aggregates decreases in the sequence: glycocholate > cholate >> dehydrocholate. It is proposed that these salts are formed by interaction of a copper(II) ion with two carboxylic groups located on the small aggregate in a sufficiently small distance. In the presence of excess cholate the precipitated copper(II) salts are dissolved. It is assumed that at high bile salt concentrations, where precipitates are not observed, larger aggregates are formed that have free carboxylate groups, which increase their solubility in aqueous solutions. For glycocholate, within the accessible concentration range and within the time-frame used (24 h for the establishment of the equilibrium), the formation of such larger aggregates was not observed, even when its "cmc" is comparable with that of cholate. The absence of formation of larger aggregates for dehydrocholate parallels its tendency not to form "micelles".