Estimated health impacts from maritime transport in the Mediterranean region and benefits from the use of cleaner fuels.

Ship traffic emissions degrade air quality in coastal areas and contribute to climate impacts globally. The estimated health burden of exposure to shipping emissions in coastal areas may inform policy makers as they seek to reduce exposure and associated potential health impacts. This work estimates the PM2.5-attributable impacts in the form of premature mortality and cardiovascular and respiratory hospital admissions, from long-term exposure to shipping emissions. Health impact assessment (HIA) was performed in 8 Mediterranean coastal cities, using a baseline conditions from the literature and a policy case accounting for the MARPOL Annex VI rules requiring cleaner fuels in 2020. Input data were (a) shipping contributions to ambient PM2.5 concentrations based on receptor modelling studies found in the literature, (b) population and health incidence data from national statistical registries, and (c) geographically-relevant concentration-response functions from the literature. Long-term exposure to ship-sourced PM2.5 accounted for 430 (95% CI: 220-650) premature deaths per year, in the 8 cities, distributed between groups of cities: Barcelona and Athens, with >100 premature deaths/year, and Nicosia, Brindisi, Genoa, Venice, Msida and Melilla, with tens of premature deaths/year. The more stringent standards in 2020 would reduce the number of PM2.5-attributable premature deaths by 15% on average. HIA provided a comparative assessment of the health burden of shipping emissions across Mediterranean coastal cities, which may provide decision support for urban planning with a special focus on harbour areas, and in view of the reduction in sulphur content of marine fuels due to MARPOL Annex VI in 2020.

A novel approach to evaluate the lung cancer risk of airborne particles emitted in a city.

Air quality still represents a main threat to human health in cities. Even in developed countries, decades of air pollution control not yet allowed to reduce pollutant concentrations in urban areas adequately. Indeed, high airborne particle concentrations are measured in several European cities; this is a main issue since particles represent a carrier for carcinogenic compounds. Numerous researches measuring the exposure to the different aerosol metrics in urban areas were recently performed, nonetheless, few data on the lung cancer risk in such environments are available. In the present paper a novel approach to evaluate the lung cancer risk related to the airborne particles emitted by the different sources located in a city is proposed and applied to a pilot case-study (i.e. an Italian city). In particular, an existing lung cancer risk model was modified and applied to assess the particle-related lung cancer "emitted" by the different sources of the city using pollutant emission factors provided by accredited emission inventory databases. Therefore, the average toxicity of the particles emitted by the city (i.e. lung cancer slope factor) and the lung cancer risk globally emitted by the city, expressed as new cases of lung cancer, were evaluated. The proposed emission inventory also allowed to identify and localize the main contributors to the overall risk emitted in a city. As an example, for the city under investigation, the research revealed that the main contributor, amongst the sources considered, is the vehicular traffic which is characterized by a lower mass fraction of carcinogenic compounds but a much higher sub-micron particle emission with respect to the other sources.

Clinical operational tolerance after kidney transplantation: a short literature review.

The clinical era of solid organ transplantation started with a renal transplantation (RT) performed between identical twins in Boston in 1954. The patient did not receive any immunosuppression, thus representing the very first case of operational tolerance (Tol). However, more than half a century later, we must admit the inadequacy of our knowledge regarding such a fundamental aspect of transplant immunology, as demonstrated by the fact that Tol has never been achieved in an intention-to-treat protocol. Herein we aim to shortly review the worldwide experience on clinical operational Tol after RT. Thus far, reports on successful cases of Tol after RT have been anecdotal: the largest series included no more than 10 individuals. We will understand that Tol can develop even in the presence of either HLA mismatches or blood group incompatibility at baseline, in the presence of anti-HLA antibodies during follow-up, as well as in patients having experienced acute rejection. Despite the lack of robust evidence, the fact that Tol is often accidentally discovered by transplant physicians during follow-up in noncompliant patients justifies the hypothesis that the real number of Tol cases might be much higher than currently reported.

Incidence of urinary tract infections caused by germs resistant to antibiotics commonly used after renal transplantation.

BACKGROUND: The inadequate utilization of antibiotics is responsible for the development of urinary tract infections (UTI) after renal transplantation (RT), through the induction of resistance to the antibiotics themselves. The purpose of this study was to evaluate the incidence of resistance to cefotaxime (CEF) and trimethoprim/sulfamethoxazole (TMP-SMX), routinely used for surgical perioperative prophylaxis and prevention of Pneumocystis carinii, respectively. MATERIALS AND METHODS: We enrolled all adult patients having received an RT from 2001 to 2006 and having a minimum follow-up of 6 months. Urine cultures (UC) were routinely performed at every outpatient clinic control and whenever required by the onset of significant clinical signs/symptoms. UTI was diagnosed by the presence of a positive UC. The endpoint of the study was the emergence of bacterial strains resistant to either CEF or TMP/SMX. RESULTS: We recorded 169 UTI in 76 patients (38 men/38 women, 33%) over a mean follow-up of 779.9+/-523.3 days. Thirty-nine patients (51%) developed more than 1 UTI episode. When gram-negative bacteria were considered, 102/144 (70.8%) tests showed resistance to TMP/SMX, while data were available in about only 7 gram-positive infections (5/7, 71%). CEF was tested less frequently with 21/43 (49%) germs resistant to this molecule. CONCLUSIONS: The onset of bacterial resistance to either TMP/SMX or CEF is frequent after RT. A wiser stricter utilization of antibiotics is mandatory. Standard antibiotic protocols should be revised.

De novo autoimmune hepatitis following liver transplantation: a case report.

De novo autoimmune hepatitis (AIH), a rare disorder first described in 1998, appears in patients with liver transplants due to autoimmune and nonautoimmune etiologies. De novo AIH occurs in 2.5% to 3.4% of allografts; children seem to have a predilection for this syndrome. We have present herein a case of a liver allograft recipient who developed chronic hepatitis associated with autoimmune features outlining the clinical course, liver histology, and response to treatment.

Lung cancer risk assessment due to traffic-generated particles exposure in urban street canyons: A numerical modelling approach.

Combustion-generated nanoparticles are responsible for negative health effects due to their ability to penetrate in the lungs, carrying toxic compounds with them. In urban areas, the coexistence of nanoparticle sources and particular street-building configurations can lead to very high particle exposure levels. In the present paper, an innovative approach for the evaluation of lung cancer incidence in street canyon due to exposure to traffic-generated particles was proposed. To this end, the literature-available values of particulate matter, PAHs and heavy metals emitted from different kind of vehicles were used to calculate the Excess Lifetime Cancer Risk (ELCR) at the tailpipe. The estimated ELCR was then used as input data in a numerical CFD (Computational Fluid Dynamics) model that solves the mass, momentum, turbulence and species transport equations, in order to evaluate the cancer risk in every point of interest inside the street canyon. Thus, the influence of wind speed and street canyon geometry (H/W, height of building, H and width of the street, W) on the ELCR at street level was evaluated by means of a CFD simulation. It was found that the ELCR calculated on the leeward and windward sides of the street canyon at a breathable height of 1.5 m, for people exposed 15 min per day for 20 years, is equal to 1.5 × 10-5 and 4.8 × 10-6, respectively, for wind speed of 1 m/s and H/W equal to 1. The ELCR at street level results higher on the leeward side for aspect ratios equal to 1 and 3, while for aspect ratio equal to 2 it is higher on the windward side. In addition, the simulations showed that with the increasing of wind speed the ELCR becomes lower everywhere in the street canyon, due to the increased in dispersion.

Characterization of airborne particles emitted by an electrically heated tobacco smoking system.

Smoking activities were recognized as a main risk factor for population. Indeed, mainstream smoke aerosol is directly inhaled by smokers then delivering harmful compounds in the deepest regions of the lung. In order to reduce the potential risk of smoking, different nicotine delivery products have been recently developed. The latest device released is an electrically heated tobacco system (iQOS®, Philip Morris) which is able to warm the tobacco with no combustion. In the present paper a dimensional and volatility characterization of iQOS-generated particles was performed through particle number concentration and distribution measurements in the mainstream aerosol. The experimental analysis was carried out through a condensation particle counter, a fast mobility particle sizer and a thermo-dilution sampling system allowing aerosol samplings at different temperatures. Estimates of the particle surface area dose received by smokers were also carried out on the basis of measured data and typical smoking patterns. The particle number concentrations in the mainstream aerosols resulted lower than 1 × 108 part. cm-3 with particle number distribution modes of about 100 nm. Nonetheless, the volatility analysis showed the high amount of volatile fraction of iQOS-generated particles, indeed, samplings performed at 300 °C confirmed a significant particle shrinking phenomena (modes of about 20 nm). Anyway, the particle number concentration does not statistically decrease at higher sampling temperatures, then showing that a non-volatile fraction is always presents in the emitted particles. The dose received by smokers in terms of non-volatile amount of particle surface area was equal to 1-2 mm2 per puff, i.e. up to 4-fold larger than that received by electronic cigarette vapers.

Variability of airborne particle metrics in an urban area.

In the present study a mobile monitoring approach (i.e. bike with onboard instruments) was proposed and applied to investigate the spatial variability of all the key airborne particle metrics in an Italian urban area from a statistical point of view. Particle number, alveolar-deposited surface area, and PM10 concentrations were measured through hand-held monitors and compared to simultaneous background concentrations by means of non-parametric tests and further post-hoc tests (Kruskal-Wallis test). Streets characterized by exposure levels statistically higher than the background levels for all the particle metrics were identified for different seasons in a pilot urban area (Cassino, Italy). A higher number of hot spots was detected for metrics affected by ultrafine particles (i.e. number and alveolar-deposited surface area concentrations) with respect to PM10. The effect of metrological requirements of the instrumentation on the proposed method was also discussed.

Risk factors that can influence kidney transplant outcome.

The survival and function of a kidney transplant are influenced by numerous immunological and nonimmunological factors. The aim of this study was to evaluate the role of a number of cadaveric donor parameters on transplanted kidney function, and in particular on the occurrence of delayed graft function (DGF) since DGF is one of the most important factors in long-term organ survival. This study looked at 143 patients who underwent kidney transplant of whom 32 displayed DGF. The creatinine levels in organ recipients, which were evaluated during a follow-up that ranged between 6 months and 4 years, were significantly higher among recipients who developed DGF after transplant (1.8 +/- 0.7 vs 1.4 +/- 0.4; P = .02). The following donor parameters were taken into consideration: history of diabetes and hypertension; creatinine levels; inotropie therapy; problems relating to hemodynamics (hypotension and/or cardiac arrest); and cold ischemia time. We observed that a donor history of hypertension (46.8% DGF vs 23.27% no DGF; P = .01) and high levels of donor creatinine prior to organ removal (1.9 +/- 1.2 mg/dL DGF vs 1.2 +/- 0.9 mg/dL no DGF; P = .007) were significant risk factors for DGF among kidney recipients. No significant differences were found for others factors between recipients with versus without DGF.

Fluorescent properties of merocyanine 540 in solutions of sialogangliosides.

The spectral modifications in the absorption and emission properties of merocyanine 540 have been evaluated in solvents of varying dielectric constants. The fluorescence behavior of dye in solutions of low dielectric constant has offered a possibility for monitoring the micropolarity of sialoganglioside micelles in aqueous solutions. Our results demonstrate that sialic acid residues markedly influence the aggregation properties of gangliosides in solution as well as the nature of dye binding to the micellar structures.

Urologic complications in kidney transplantation.

Urologic complications in kidney transplantation have an incidence ranging from 3% to 20%, representing an important cause of organ loss. From January 2001 to September 2004, 123 renal transplantations were performed using an immunosuppressive protocol including basiliximab, mycophenolate mofetil, calcineurin inhibitors, and steroids. The surgical technique was vascular anastomoses to external iliac vessels, and ureteral anastomosis according to Lich Gregoire technique using a JJ ureteral stent. We report 5 renal complications (4.2%) and 4 extrarenal complications (3.5%), the majority of which required corrective surgery. The surgical strategy uses the clinical condition of the donor and the recipient; the anatomic anomalies of the graft, and a reduced cold ischemia time. Moreover, a reduction in acute rejection episodes and immediate renal function has been fundamental to reduce urologic complications. In fact, the main cause of urologic complications is ureteral ischemia, linked both to backtable surgery and to rejection episodes. Another important factor in the reduction of early urologic complications has been the routine use of a JJ stent, which allowed us a conservative approach in this setting.

Malignancies after kidney transplantation.

The most effective treatment of end-stage renal disease is renal transplantation; its superiority to prolong the longevity of patients is well established. Patient and graft survivals have improved with more potent immunosuppression but this advance has been associated with an increased incidence of cancer. The aim of this study was to assess the prevalence of cancer among 265 kidney transplant recipients engrafted between 1968 and October 2004. The overall prevalence of de novo malignancies was 3%. The mean age at diagnosis was 53.3 years (range, 28-63 years) and the duration of the transplant was 11.6 years (range, 0.3-33 years). One patient among 127 (0.8%) who had a history of less than 3 years under immunosuppression, developed a posttransplantation lymphoproliferative disorder (PTLD). Among the 138 patients who had more than 3 years immunosuppression, 7 (5%) developed neoplasms of vulva, colon, native kidneys, prostatic gland, and ovary. One patient was affected by de novo carcinoma in the transplanted kidney. Compared with other published studies, our early cancer prevalence is low, possibly due to a careful history before grafting, good HLA matching, and abstinence from anti-T-cell therapy for treatment of acute rejection episodes. The low level of immunosuppression may account for the low prevalence of neoplasia. The risk of developing a malignancy increases with long-term immunosuppression, comparable with most reports.

Nuclear DNA strand breaks during ethanol-induced oxidative stress in rat brain.

Free radical-mediated oxidative damage has been implicated in the pathophysiological mechanisms of apoptosis. In this study we report that statistically significant strand breaks were induced primarily in the hippocampus and cerebellum during chronic, and not acute, ethanol treatment. Damage to DNA observed in hippocampus and cerebellum was also correlated with significant modification in the activities of mitochondrial respiratory complexes I and IV and with a significant increase in lipid peroxidation products. This finding lends support to the fact that hippocampus and cerebellum are brain areas particularly vulnerable to redox changes induced by alcohol intoxication, suggesting lower threshold levels of ethanol tolerance.

Stress proteins and SH-groups in oxidant-induced cell damage after acute ethanol administration in rat.

It is generally accepted that lipid peroxides play an important role in the pathogenesis of ethanol-induced cellular injury and that free sulfhydryl groups are vital in cellular defense against endogenous or exogenous oxidants. It has been observed that oxidative stress induces the synthesis of the 70-kDa family of heat-shock proteins (HSPs). Furthermore, induction of HSPs represents an essential and highly conserved cellular response to a variety of stressful stimuli. In the present study, we measured the intracellular levels of HSP 70 proteins after administration of mild intoxicating and grossly intoxicating doses of ethanol to rats. Our results demonstrate that elevated doses of ethanol induce HSP in various brain areas, namely, cerebellum, hippocampus, and to a lesser extent, striatum or liver. Induction of HSP 70 protein was correlated with a marked depletion of intracellular bound thiols and a decrease in lipid peroxidation measured as MDA formation. These studies support the hypothesis that a redox mechanism may be involved in the heat-shock signal pathway.

Stress proteins and SH-groups in oxidant-induced cellular injury after chronic ethanol administration in rat.

It is generally agreed that lipid peroxides play an important role in the pathogenesis of ethanol-induced cellular injury and that free sulfhydryl groups are vital in cellular defense against endogenous or exogenous oxidants. It has been observed that oxidative stress induces the synthesis of the 70-kDa family of heat-shock proteins (HSPs). Induction of HSPs represents an essential and highly conserved cellular response to a variety of stressful stimuli. In the present study we measured in various brain areas and in liver the intracellular levels of HSP70 proteins, sulfhydryl groups and the antioxidant enzyme status after chronic administration of mild intoxicating doses of ethanol to rats. Expression of HSP70 in response to alcohol administration was particularly high in the hippocampus and striatum. In these brain areas, the increase in HSP70 protein levels occurred in absence of significant changes of antioxidant enzyme activities and was correlated with a marked depletion of intracellular bound thiols and with a decreased susceptibility to lipid peroxidation. Lower levels of HSP70 induction were found in cortex and cerebellum and were associated to decreases in SOD and CAT enzyme activities, with a lower depletion of protein bound thiols and with an increased susceptibility to lipid peroxidation. This study agrees with our previous results performed on acute alcohol intoxication and supports the hypothesis that HSP70 induction protects the different brain areas against oxidative stress.

Urinary excretion of IgG and alpha(1)-microglobulin predicts clinical course better than extent of proteinuria in membranous nephropathy.

In idiopathic membranous nephropathy (MN), the main predictors for progression to chronic renal failure (CRF) are the amount of proteinuria and extent of tubulointerstitial damage. The aim of this study is to evaluate whether urinary excretion of proteins reflecting the alteration of permselectivity in the glomerular capillary wall, such as immunoglobulin G (IgG), and the reabsorption impairment of low-molecular-weight proteins, such as alpha(1)-microglobulin (alpha(1)m), correlates with the extent of tubulointerstitial damage and have a predictive value for functional outcome and response to therapy better than 24-hour proteinuria. In 78 patients with MN, urinary excretion of albumin, transferrin, IgG, and alpha(1)m was measured by immunonephelometry in second-morning urine samples and expressed in milligrams per gram of urinary creatinine (uCr). In 48 patients with characterization of proteinuria and renal biopsy performed at the same time, excretion of IgG (P = 0.0087) and alpha(1)m (P = 0.0024), but not albumin (P = 0.37), transferrin (P = 0.38), or 24-hour proteinuria (P = 0.32), was associated significantly with the extent of tubulointerstitial damage (score, 0 to 1 versus >/=2). Only alpha(1)m excretion was associated significantly with global glomerular sclerosis (P = 0.0032) and arteriolar hyalinosis (P = 0.0004). Moreover, urinary excretion of alpha(1)m was significantly dependent on IgG excretion (r = 0.67; P = 0.0001), but not on albumin (P = 0.66) or 24-hour proteinuria (P = 0.07). Functional outcome could be evaluated in 38 patients with nephrotic syndrome and baseline normal renal function (serum creatinine, 0.99 +/- 0.20 mg/dL; follow-up, 44 +/- 22 months). Remission was 100% versus 20% in patients with IgG excretion less than 110 mg/g uCr versus 110 mg/g uCr or greater (P = 0.0001) and 77% versus 17% in patients with alpha(1)m excretion less than 33.5 mg/g uCr versus 33.5 mg/g uCr or greater (P = 0.0009), respectively. In patients with IgG and alpha(1)m excretion less than or greater than the cutoff value, progression to CRF was 0% versus 35% (P = 0.0026) and 0% versus 58% (P = 0.0001), respectively. Nineteen patients treated with immunosuppressive therapy were compared with 19 untreated patients. There was no difference in remission or progression between treated and untreated patients when IgG and alpha(1)m excretion were less than the cutoff value. There was a significant difference for progression to CRF between treated and untreated patients when alpha(1)m excretion was greater than the cutoff value (17% versus 100%; P = 0.0076). In conclusion, IgG excretion is associated significantly with the extent of tubulointerstitial damage and alpha(1)m excretion. This observation supports the hypothesis that IgG may be the toxic moiety of proteinuria. Excretion of IgG and alpha(1)m has a significant predictive value for both remission and progression and is useful to identify patients who are at risk for progression and for whom treatment with immunosuppressive therapy is indicated soon after diagnosis.

SDS-PAGE patterns and polymeric albumin in proteinuria of lupus glomerulonephritis.

Proteinuria was characterized by SDS-PAGE and by immunoblotting with anti-human albumin sera for the detection of urinary polymers of albumin (PA) in 40 patients with biopsy proven lupus glomerulonephritis (LN) (6 pts class III WHO, 24 pts class IV, 10 pts class V) with various clinical presentations (nephrotic syndrome with normal or impaired renal function, 14 pts; urinary abnormalities with normal or impaired renal function, 21 pts; clinical remission, 5 pts); in 25 pts, for whom the characterization of proteinuria and the renal biopsy were performed at the same time, the activity and chronicity index scores were calculated. The mixed SDS-PAGE patterns, characterized by the presence of low molecular weight proteins, were the more frequently found; the mixed patterns were significantly associated with interstitial leukocyte infiltration (p = 0.05) and glomerular sclerosis (p = 0.046) and nonsignificantly associated with higher values of serum creatinine; no SDS-PAGE pattern had predictive value on functional outcome at 36 months. Albumin polymers were present in 67% of pts; in active disease they were present in 33% of class III, in 100% of class IV and in 45% of class V WHO (p = 0.026); PA were not present in 5 pts with clinical remission (4 class IV and 1 class V WHO). The presence of PA was significantly associated with high values (> 10) of activity index (p = 0.009) and with extracapillary proliferation (p = 0.041). Serum creatinine was lower in patients without PA (Scr 1.0 +/- 0.4 mg/dl) than in those with PA (Scr 1.5 +/- 1.0 mg/dl), but the difference was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Formation of propionate after short-term ethanol treatment and its interaction with the carnitine pool in rat.

Organic acidurias are genetic disorders of mitochondrial metabolism that lead to the accumulation in tissues and biological fluids of organic acids. It has been demonstrated that interaction of carnitine with the cellular CoA pool, through the production of acyl-carnitines, is potentially critical for maintaining normal cellular metabolism under conditions of impaired acyl-CoA use and that exposure of humans and other mammals to ethanol effects leads to impairment of mitochondrial function. The aim of the present study was to evaluate the role of ethanol on urinary excretion of short-chain organic acids and endogenous carnitines in rats. The data reported show that ethanol significantly increases urinary excretion of propionate, methylmalonate, as well as free acetate, butyrate, pyruvate, lactate, and beta-hydroxybutyrate. Furthermore, the increased formation of propionate and methylmalonate was dependent on the dose of ethanol; did not require the metabolism of ethanol, as was shown in experiments with pyrazole treatment of ethanol rats; and appears to be mediated by beta-adrenergic mechanisms because propranolol almost completely suppresses propionate accumulation. Alcohol administration also increased excretion of specific acyl-carnitines, corresponding to the accumulating acyl groups, whereas excretion of free carnitine was significantly reduced, with respect to control values. The data presented indicate that the short-term ethanol administration is associated with increased excretion of selected organic acids. This study suggests that endogenous carnitine pool might play a role against the deleterious effects of accumulating short-chain organic acids.

Structural characterization and solution properties of an acidic branched (1-->3)-beta-D-glucan from Aureobasidium pullulans.

An acidic exopolysaccharide was isolated from a selected strain of Aureobasidium pullulans. On the basis of spectroscopic and chromatographic techniques, the polymer was identified as a beta-D-glucan containing a main chain of (1-->3)-linked beta-D-glucopy-ranosyl units substituted at the O-6 position by single beta-D-glucopyranosyl side chains. The ratio of units in the main chain to units in the side chain was found to be 1.4:1. The ionic character of this exopolysaccharide is due to the presence of malate residues which are linked to the polymer through ester bonds. The degree of substitution was estimated to be very low (0.05). In aqueous solution no signals are present in the NMR spectra strongly suggesting that the polymer adopts a rigid ordered conformation as further confirmed by rheological data. A solvent-induced conformational transition was observed in DMSO in which NMR spectra with good signal-to-noise ratio were obtained. The solution behaviour of the polymer is similar to that of other branched (1-->3)-beta-D-glucans in spite of both the degree of branching and the substitution with malate groups.

Effects of Metadoxine on cellular status of glutathione and of enzymatic defence system following acute ethanol intoxication in rats.

The aim of the study was to determine whether a combination of pyridoxine and pyrrolidone carboxylate (PCA) could influence the antioxidant defence system in hepatic and extrahepatic tissues during acute ethanol administration. The results showed that ethanol treatment led to a significant depletion of reduced glutathione and increase in oxidized glutathione (GSSG) in the different organs, associated with decreased activity of glutathione reductase. Pretreatment of animals with Metadoxine (PCA + pyridoxine) one hour before ethanol administration produced a significant protection against glutathione (GSH) depletion in the different organs examined. This was consistent with an increase in glutathione reductase activity. In view of the fact that free thiol compounds such as glutathione are vital in cellular defence against oxidants and that decreases in reduced glutathione precede lethal cell injury resulting from free radical accumulation, our study supports the effectiveness of Metadoxine as a useful therapeutic agent effective in the management of all those pathological conditions where a severe imbalance of cellular redox state seems to take place as a result of the generation of free radical species.