001) from 12.15 to 2.0 μg/mL (normal range: < 2.0 to 6.6 μg/mL) and GM3 decreased by 74% from 19.4 to 5.9 μg/mL (normal range: 5.0 to 9.2 μg/mL). Bone pathology represents a primary and often this website progressive clinical

feature of GD1, perhaps caused by a disruption of the normal bone remodeling process [10] and [11]. Long-term eliglustat treatment maintained improvements in both osseous and marrow bone compartments. Fifteen of 19 patients had evaluable bone data over the 4‐year period, 12 of whom had osteopenia or osteoporosis of the lumbar spine at baseline. With eliglustat treatment, the mean bone mineral density (BMD) T-score for the lumbar spine increased significantly (P = 0.014) by 0.8 (9.9% in BMD g/cm2) from baseline see more to 4 years, an improvement that moved the mean T-score out of the osteopenia range (− 1.0 to − 2.5) and into the normal

range (− 1.0 to 1.0) ( Fig. 3). Femur MRI results showed stabilized or improved bone disease over 4 years. Dark marrow, which was present in 18 of 19 (95%) patients at baseline, improved in 9 patients (50%), was stable in 8 patients (44%), and was possibly enlarged in 1 patient (6%) at 4 years [12]. Lytic lesions present in 8 of 19 (42%) patients at baseline remained stable and no new lesions were identified. No bone crises were reported for the duration of the trial. Safety outcomes for the first 2 years of eliglustat treatment have been published [4] and [5]. No substantial new safety issues have arisen since then. After 4 years, a total

of 191 treatment-emergent adverse events were reported in 23 patients, of which 74% were classified as mild and 95% were assessed as unrelated to treatment. Ten related treatment-emergent adverse events, all of which were mild, were reported in eight patients; each related adverse event occurred in one or two patients. All three patients who had peripheral nerve treatment emergent adverse events considered related to treatment were asymptomatic and had discordant neurological exam and nerve conduction findings; all have continued eliglustat treatment [5]. Most related treatment-emergent adverse events (7/10) occurred PARP inhibitor during the first 74 days of treatment. Over 4 years, five serious treatment-emergent adverse events were reported in three patients, all during the first year of treatment and as previously reported. No deaths occurred. In 4 years, there were seven discontinuations; four in the first year (two due to pregnancy and two due to asymptomatic nonsustained ventricular tachycardia after one dose) [4] and [5], two during the second year (pregnancy and bone lesion) [4] and [5], and one during the third year (administrative). Long-term follow-up of eliglustat treatment for previously untreated GD1 patients demonstrated continuation and maintenance of improvements in hematologic parameters, organ volumes, disease-related biomarkers, and bone parameters.

Although, as a type III interferon that shares signaling pathways with type I interferons, 24 it most likely protects via a direct mechanism on the hepatocyte, possibly inhibiting HCV replication like the related molecule IFN-λ1 25 or rendering cells less susceptible to infection. 26 Additionally, IFN-λ2 does not appear to directly affect NK cells. 27 Therefore, there is a biologic rationale for the separation of these 2 genetic effects. One model for resistance to, or resolution of, HCV

infection is that possession of multiple independent protective factors may synergize to provide protection against chronic infection so that individuals with more protective factors have a greater chance of resolution of HCV infection. Our data do not support this hypothesis. Instead, we propose that KIR:HLA and IL28B define 2 genetically distinct subpopulations of individuals selleck chemicals who are relatively protected against chronic HCV infection. Future genetic studies of resolution of HCV infection should stratify for these genotypes to take this heterogeneity into account. The authors thank Dr Bernard North for statistical advice. “
“Evidence from

a meta-analysis of longitudinal studies among adults indicated an association between whole grain (WG) intake and reduced risk of type 2 diabetes, cardiovascular disease, and overweight [1]. Whole grain intake among school-aged children (third-sixth grades) and female adolescents was associated with lower body mass index z-scores and lower risk of overweight in young adulthood, respectively Selleckchem OSI744 [2] and [3]. The protective health benefits of WG have been attributed to numerous components including total dietary fiber and bioactive compounds

in bran and germ such as vitamins, minerals, trace elements, polyphenols, alkylresorcinols, and Suplatast tosilate carotenoids [4], [5], [6] and [7]. US Dietary Guideline recommendations indicate that at least half of all grains be consumed as WGs [8], which typically includes at least 3 ounce equivalents (oz eq)/d for adults and 1.5 to 4 oz eq/d for children/adolescents, depending on age, sex, and energy needs [8]. However, US National Health and Nutrition Examination Survey (NHANES) 1999 to 2004 data showed that only 1.5% to 4.3% of children/adolescents, 4.8% of adults aged 19 to 50 years, and 6.6% of adults aged 51+ years consumed at least 3 WG oz eq/d [9] and [10]. Most children/adolescents and adults also do not consume the recommended grams/day of total dietary fiber [11]. Adequate Intake (AI) values of 19 to 25 g/d were established for children aged 1 to 8 years, 31 to 38 g/d for boys aged 9 to 18 years, 26 g/d for girls aged 9 to 13 years, and 21 to 38 g/d for women and men 19 years or older from Dietary Reference Intakes [12]. Based on data from NHANES 2003 to 2006, less than 3% of children/adolescents had a usual fiber intake that was greater than the AI [11].

In other words, adaptation measures of low-income groups are constrained by economic barriers [5]. While some organisations offer micro-credit, most fishing-dependent people do not have access to it; in line with Amin et al. [30] and Helms [31] who found that micro-credit usually does not often reach the most vulnerable groups. The direct and indirect impacts of social barriers in constraining adaptation

support the theory that individual and social characteristics interact with underlying values to form barriers [6]. Our results also support Ruxolitinib purchase the evidence that institutional barriers play an important role to constrain adaptation to stresses [41], [42], [43] and [60]. If institutions fail to respond to changing conditions and risks, a system’s vulnerability can be exacerbated [61]. Lack of enforcement of fishing regulations, and the coercion of crews to fish by Padma boat owners and captains reduce the fishermen’s ability to adapt to cyclones. The presence of boat owners’ trade union further reinforces their power.

Thus individual adaptation is constrained by social norms and institutional processes as well [19] and [21]. The fishing activities will face further challenges due to increased frequency and intensity of cyclones in the future [51] and [52]. Selleck AG14699 Reduction of greenhouse gas emissions is necessary to overcome the limits, which need to be complemented with planned adaptation. There is no single adaptation which would overcome all barriers. Several complementary

measures are needed, including improved fishing boats, improved cyclone forecasts and radio signal, increased access to low-interest credit, fish market and insurance, enforcement of fishing regulations and maritime laws, development of human capital through education and skills, and creation of livelihood alternatives. This study has identified and characterised a number of limits and barriers to adaptation of fishing activities to cyclones in two Bangladeshi fishing communities. The natural limits are similar in both communities but technological, economic, social and formal institutional barriers are more contextual. These limits and barriers are also interrelated and combine to constrain adaptation, for example, completion of fishing trips, coping with cyclones at sea, safe return selleck chemical of boats from sea during cyclones, timely responses to cyclones, and fishermen’s livelihood diversification from risky fishing activities. Global climate change mitigation is essential over the longer term to overcome the limits to adaptation and to build resilience, because adaptive capacity may be limited to only lower levels of climate change (≤2–3 °C) [1]. Given the interrelated nature and combined influence of many barriers, overcoming them is complex and needs planned adaptation strategies. Both internal and external factors pose barriers to adaptation and some barriers are reinforced by others.

Dent disease is an X-linked inherited condition caused by a mutation in the CLCN5 gene. The condition

is characterized by low-molecular-weight proteinuria, nephrocalcinosis, hypercalciuria, nephrolithiasis, and chronic kidney disease. The clinical presentation is often insidious with many patients remaining asymptomatic throughout childhood; however, signs and symptoms of nephrocalcinosis and hypercalciuria are not uncommon in childhood. The defect is in proximal tubular function, and occasionally glucosuria, aminoaciduria, metabolic acidosis, and hypophosphatemia may all occur as part of an associated partial Fanconi syndrome. In a minority of patients, the Dent phenotype results from a mutation in the OCRL gene (Dent 2), which is also involved in the oculocerebrorenal syndrome of Lowe. Bartter syndrome is an AZD2014 autosomal recessive condition characterized by renal salt wasting, hypokalemia, metabolic alkalosis, hypercalciuria, and normal serum magnesium levels. Children younger

than 6 years typically present with salt craving, polyuria, dehydration, emesis, constipation, and failure to thrive. Severe polyhydramnios, prematurity, and occasionally sensorineural deafness are the hallmark features. Mutations in the SLC12A, KCNJ1, and BSND genes (Bartter syndrome type I, type II, check details and type IV, respectively)

typically result in severe dysfunction of the thick ascending limb (TAL) of the loop of Henle in the neonatal period (neonatal Bartter syndrome). Mutations in the ClCKB gene (Bartter syndrome type III) usually cause milder TAL dysfunction and often present outside the neonatal period (classic Bartter syndrome). FHHNC often presents in childhood with seizures or tetany caused by hypomagnesemia. Other clinical manifestations include frequent urinary tract infections (UTI), polyuria, polydipsia, failure to thrive, nephrolithiasis, and progressive renal failure.19 FHHNC is an autosomal recessive condition caused by mutations in either the CLDN-16 or CLDN-19 genes. Homozygous CLDN-16 or -19 mutations are associated with impaired Vitamin B12 tight junction integrity in the TAL, urinary magnesium and calcium wasting, and resultant hypomagnesemia. Patients usually develop the characteristic triad of hypomagnesemia, hypercalciuria, and nephrocalcinosis. Profound visual impairment characterized by macular coloboma, significant myopia, and horizontal nystagmus can been seen in association with CLDN-19 mutations. 20 Primary dRTA is an inherited condition characterized by systemic acidosis as a result of the inability of the distal tubule to adequately acidify the urine.

Such pharmacologic treatments are now commonly used on children (sometime extremely young) during long periods (2–5 years) with the rationale to maximize the impact on a growing skeleton. However, some concerns have been raised about the equivocal efficiency on the fracture reduction [4] and [5], the accumulation of those long life drugs

and the impact of inhibiting bone remodelling over long periods, which results in the build-up of poor quality, highly mineralized bone [1] and [6]. GDC-0199 mouse It is recognized that the bone tissue is highly responsive to dynamic loading and is able to adapt its architecture and mass to the mechanical loading environment [7], [8] and [9]. Bone remodelling is sensitive to strain magnitude [10] and [11], frequency [12] and [13], number of loading cycles [14], strain rate [15] and rest periods between stimulation [16]. In addition to bone response to high peak strains [17] and [18], there is also evidence of bone adaptation at low strain but high frequency loading [9] and [19]. Because high strain exercises in patient suffering from OI may result in fracture, high frequency low amplitude whole body mechanical

vibration (WBV) is an attractive low-impact and drug-free approach to stimulate bone formation. The therapeutic impact of Stem Cell Compound Library WBV treatment has been observed on muscle strength, motion, posture and bone density in various osteopenic populations: young women [20] and [21], post-menopausal women [22], [23], [24] and [25] or children with disabling conditions like cerebral palsy [26] or with OI [27] but no effect has been observed on healthy adults [28]. However more investigations are required to confirm the impact of WBV on

bone mass and to identify the most efficient vibration parameters and the most responsive target population [29], [30], [31], [32] and [33]. Numerous studies have investigated the influence of WBV on bone formation using a large variety of animal models (sheep, rat, mouse) [34], [35], [36] and [37], age (growing, young or old adults) [38], [39] and [40], L-gulonolactone oxidase vibration frequency (from 20 to 90 Hz) [41], [42] and [43], maximum peak acceleration (from 0.1 to 3 g) [43] and [44], treatment duration (from 10 to 30 min) and treatment length (from 2 weeks to 1 year). A significant osteogenic effect was observed in the trabecular bone of both the femoral condyle and tibial metaphysis of adult sheep (1 year treatment, 30 Hz, 0.3 g) [35] and [36]. In adult mice, an osteogenic response to WBV is observed in the tibial metaphysis with a non-dose dependent response to acceleration (5 weeks treatment, 45 Hz, 0.1, 0.3 and 1 g) [44]. An influence of the mouse genotype was observed: the osteogenic response to WBV inversely correlated to the low (C57Bl/6J), medium (BALB/c) or high (C3H) bone density of the mouse strain (2 to 3 weeks treatment, 45 Hz, 0.25 g) [37].

05). The differences in biomarker values PI3K inhibitor between the 2 groups are listed in Table 2. The levels of the bone formation markers serum OC and serum BAP, and those of the bone degradation markers urine DPD, urine NTX, and serum CTX were not significantly different between the 2 groups; only levels of serum PTH showed a significant difference (P < 0.05). Regarding the serum total calcium and albumin-adjusted total calcium, the

values in BRONJ group (n = 29; 8.85 ± 0.47 and 9.09 ± 0.84, respectively) were significantly lower than that of Non-BRONJ group (n = 24; 9.36 ± 0.51 and 9.50 ± 0.45, respectively) (P < 0.05). The serum CTX level in reference to a 150 pg/mL cutoff was also not significant for the development

of BRONJ (P > 0.05). When considering the daily trend of biomarker levels (for OC, DPD, CTX, and NTX) after BP discontinuation in BRONJ patients, the mixed model analysis with repeated measures revealed no time trends for OC (estimated regression coefficient [β] = 0.031, 95% CI − 0.001 to 0.063, P = 0.057), DPD (β = 0.004, 95% CI − 0.028 to 0.020, P = 0.745), and NTX (β = 0.153, 95% CI − 0.036 to 0.342, P = 0.110), with the exception of CTX (β = 0.002, 95% CI 0.000 to 0.003, P = 0.007) ( Fig. 1). That is, the CTX levels of BRONJ patients increased by 2 pg/mL per day from the baseline mean of 177 pg/mL after BP discontinuation. In the ROC Inhibitor high throughput screening curve analysis for PTH, which was a significant biomarker, the AUC was 0.719 (95% CI 0.556–0.882, P = 0.009) ( Fig. 2). The cutoff value with both maximal sensitivity and specificity was > 41.52 pg/mL. At this cutoff, the sensitivity and specificity of PTH for

the prediction of BRONJ development was 56.5% and 86.7%, respectively. For CTX, the AUC was 0.619 (95% CI 0.499–0.730, P = 0.069) and the cutoff value was ≤ 0.094 ng/mL (sensitivity, 29.7%; specificity, 89.2%). When 150 pg/mL was set as the standard, the sensitivity was 54.1% and the specificity was 35.1%. This study was conducted to investigate the possible associations of the bone biomarkers OC, CTX, NTX, DPD, BAP, and PTH as risk predictors of BRONJ. Thus, a case–control study involving patients with a diagnosis of BRONJ and an age- and gender-matched Pyruvate dehydrogenase control group was conducted. This study was important in that it was an investigation of controversial bone biomarkers involving a relatively large BRONJ patient sample size, at a single institution with a single standard for BRONJ diagnosis criteria and sampling protocols. BPs are most often used in the nonhormonal treatment of osteoporosis and are also widely used for cancer metastasis and various bone diseases. Their use has been increasing steadily, and the associated incidence of BRONJ is also increasing [18].

“
“Head direction cells are specialized neurons that fire only when an animal faces a certain range selleck products of directions in the horizontal plane, independent of the location and speed of the animal [2 and 3]. These neurons, which exist in a variety of brain regions [11], are already almost fully developed at the time when animals begin exploring the outside world, at the age of postnatal day 16–18 (P16–P18), a few days after the eyes open at P14–P15 [8 and 9]. The present study was designed to determine whether head direction tuning is present at even earlier ages, before the eyelids open and at a time

when rat pups still spend nearly all of their time in the nest [12]. We specifically asked whether directional tuning differences are maintained across experiences. If relative firing directions are maintained from one experimental trial to another, before the appearance of vision, it would point to strong innate components in the mechanism for directional tuning in the brain. A total of 163 cells were sampled from 14 rat pups while the pups moved around twice for 10 min in a circular or square recording box. Eighty-six of these cells were recorded

during the last 3–4 days before eye opening; 77 cells were recorded 1–2 days after eye opening. No cells were recorded for more than one block of trials. The total number of recording blocks (sessions) was 57. Pre-eye-opening data were obtained on P11 in one rat, P12 in three rats, P13 in six rats, P14 in eight rats, and P15 in one rat; post-eye-opening data were collected on P14 in one rat, P15 in eight rats, and P16 in eight Metformin price rats. Individual rats were recorded for 2–6 days. The tetrodes were placed in presubiculum in seven rats, in parasubiculum

in four rats, at the border between pre- and parasubiculum in two rats, and in medial entorhinal cortex (MEC) in one rat (Figure 1; Figure S1 available online). The tetrodes were distributed across deep and superficial layers of pre- and parasubiculum and deep layers of MEC. The pups moved freely across the recording arena and covered the entire range of head directions. Median running speeds increased from 7.6 ± 0.1 cm/s before eye opening to 9.4 ± 0.2 cm/s after eye opening (means across animals ± SEM; t(102) = 6.9, p < 0.001). Mean coverage of the recording box increased from 85.7% ± 0.8% to 91.5% ± 0.8% (t(102) = 5.0, p < 0.001). Head-direction-tuned cells were Protirelin present from the first day when cells could be identified in the target area (P11 and upward; Figures 1 and 2A). To compare directional tuning before and after eye opening, we computed, for each cell, the length of the mean vector for the distribution of firing rates across the 360° of possible head directions. Cells were classified as head direction cells if their mean vector was longer than the 95th percentile of a distribution of mean vector lengths for shuffled firing rates (Figure 2B). Before eye opening, 59 out of 86 cells (68.6%) passed this criterion.

, 2009). Soil and water conservation programs in China were first legislated in the 1950s following concern about local agricultural and industrial productivity and flooding downstream (Shi and Shao, 2000). Implementation at large spatial scales (e.g. 0.92 M km2 of land terracing, tree and grass planting, and construction of selleck compound sediment trapping dams), mostly in the Yellow and Yangtze basins, has reduced sediment fluxes to coastal waters by an estimated 11.5 Gt during 1959–2007 (Chu et al., 2009). Terrestrial fluxes of N and P to coastal waters have been reduced following management of point sources, such as waste water treatment plants, phosphate mines and P-detergents (Boesch, 2002 and Cloern, 2001) (Tables 1c and 2). For example,

regulation has reduced the contributions from waste water treatment plants and industrial discharges to total annual average N and P loads to the Danish coast from ∼50% to <10%, and from 59% to ∼20%, respectively, over 14 years (Carstensen et al., 2006). The check details nutrient regulation in Denmark followed lobster mortality in coastal waters in the 1980s which was attributed to algal blooms and hypoxia induced by agricultural nutrient run-off (Windolf et al., 2012). Similar declines in nutrient loads from point sources have resulted in reductions in coastal nutrient and chlorophyll a (chl a)

concentrations ( Greening and Janicki, 2006), enhanced benthic irradiance ( Greening and Janicki, 2006), seagrass recovery ( Tomasko et al., 2005), and concomitant decline in macroalgae ( Cardoso et al., 2010 and Vaudrey et al., 2010), including on coastal coral reefs ( Laws and Allen, 1996 and Smith et al., 1981). Further recovery, including to a coral-reef dominated state, may be partly constrained by nutrient sources other than point sources ( Hunter and Evans, 1995), as well as obscured by increases in human population, changes in diffuse sources and

variation in freshwater discharge ( Williams et al., 2010). Reducing diffuse source loads becomes increasingly important where point source discharges comprise only a small percentage of the total N and P loads, such as in the Great Barrier Reef (GBRMPA, 2009). Major recent reviews provide recommendations to reduce excessive or inappropriate input of N and P from diffuse sources such as agriculture, selleck screening library fossil-fuel and animal husbandry (Canfield et al., 2010, Elser and Bennett, 2011, Galloway et al., 2008 and Vitousek et al., 2009). Deliberate management of agricultural diffuse pollution has contributed to reducing nutrient fluxes to coastal waters in Denmark (Windolf et al., 2012) and The Netherlands (Duarte et al., 2009) within decades (Tables 1c and 2). Moreover, decreasing nutrient fluxes have been measured in several Eastern European rivers, namely the Danube, Daugava, Elbe, Leilupe, Oder and Vistula rivers, in the years following economic decline and associated drop in agricultural subsidies in the early 1990s (Duarte et al., 2009, GEF-UNDP, 2006, Mee, 2001, Pastuszak et al.

The twelve background LVs were divided into three groups: demographic variables (gender, age, education level and occupation); health- and treatment-related variables (disease burden, cardiovascular disease experience, treatment explanation satisfaction, treatment time and side Gefitinib order effects); and health locus of control variables (on three levels: internal, chance and powerful others). The average age of the study population was 64.2 years (S.D. ± 9.5), and the group consisted of slightly more men (51.1%) than women (48.9%). Compulsory school was the most commonly completed education level (40.0%). Approximately 40.6% of the group were in full-time or part-time work, while the remaining 59.4% were unemployed or

retired from the work market. The

distribution of demographics and key variables in the study population is shown in Table 1. In the whole group, 54.5% of patients were classified to have high adherence, and 45.5% were classified to have low adherence to their statin treatment. About one-fifth of the group reported a high disease burden (suffering from five or more diseases) and half of the group had between two and four diseases. Overall, 72.8% of the patients did not report any CVD experience, and therefore received their treatment as primary prevention, 27.2% of the group reported at least one CVD experience, so received their treatment as secondary prevention. The majority of the group did not report any side effects, NU7441 molecular weight but 11.9% did experience some side effects. The Mann–Whitney U test in Table 1 showed no significant difference on internal or chance between patients with low and high adherence, only small differences were seen on the MHLC index scales. Several of the associations outlined in the research framework (Fig. Thiamine-diphosphate kinase 1) were also significant in the correlation matrix (Table 2). The highest correlation to the adherence variables was seen with the perception of necessity of treatment. The indicator variables were tested for multicollinearity, and no variable had over 2.5 in VIF, which indicates that the risk for multicollinearity can be considered to be low. These imply acceptability of using

a structural equation model. A PLS estimation procedure was used to examine the hypothesized relationships (Fig. 2) between constructs depicted in the theoretical framework (Fig. 1). The SEM analysis showed a significant relationship between adherence and necessity of treatment (β = 0.15, p = 0.010), but not with concern ( Table 3). The explanatory variables were also tested directly against adherence, and it was found that side effects (β = −0.14, p = 0.006) had a significant effect on adherence. The analysis showed that education level (β = −0.10, p = 0.033), disease burden (β = 0.20, p < 0.001), CVD experience (β = 0.17, p < 0.001), satisfaction with treatment explanations made by a physician (β = 0.13, p = 0.008), treatment time (β = 0.14, p < 0.001) and powerful others in locus of control (β = 0.33, p < 0.

The present finding shows for the first time that there is enhanced

protein expression of the Cu/Zn- and Mn-SOD isoforms as the same time that there is enhanced production of the superoxide anion in the pulmonary artery of rats exposed in vivo to PM2.5. It was previously demonstrated that PM2.5 exposure causes oxidative stress in aortic tissue and in macrophages ( Wan et al., 2010). In addition, in macrophages cell, in vitro PM Crenolanib manufacturer exposure enhances gene expression of Cu/Zn-SOD ( Wan et al., 2010) and the protein expression of the antioxidant enzymes catalase and heme oxygenase-1 ( Xiao et al., 2003). Therefore, enhanced expression of SOD isoforms could be a secondary mechanism activated in response to enhanced superoxide anion production induced by PM2.5 as a protective pathway. The proinflammatory cytokines IL-1β, IL-6 and TNF-α have emerged as biomarkers and mediators of oxidative stress and endothelial dysfunction in several cardiovascular diseases (Ungvari et al., 2003 and Wan et al., 2010). In the present study, we observed that pulmonary arteries from urban PM2.5-exposed animals showed enhanced TNF-α protein expression despite there being no changes in IL1-β and IL-6. Thus, inhaled PM2.5 could directly induce endothelial dysfunction

by stimulating TNF-α protein synthesis. This hypothesis is in agreement with a prior study demonstrating that acute in vitro exposure to fine manufactured PM increases the release of TNF-α in isolated rat pulmonary CDK activity Fossariinae arteries and dexamethasone (an anti-inflammatory drug) prevented the reduction of acetylcholine-induced

relaxation in these vessels ( Courtois et al., 2008). It is known that the pro-inflammatory cytokine TNF-α can impair eNOS gene and protein expression, thus reducing NO synthesis ( Anderson et al., 2004). In the present study we found a significant negative correlation between TNF-α protein expression and maximal relaxation to acetylcholine in pulmonary arteries from in vivo PM2.5-exposed rats, suggesting that the higher TNF-α protein expression induced by air pollution is strongly related with the endothelial dysfunction of pulmonary circulation. Deposition of PM on alveolar epithelium induces infiltration of inflammatory cells, thus increasing the release of local proinflammatory factors that can reach pulmonary and systemic circulation and trigger secondary inflammation (Seaton et al., 1995). Moreover, elemental components of PM per se or after macrophage phagocytosis can pass through the alveolar-capillary membrane and induce peripheral effects ( Lehnert, 1992). Our findings for peripheral blood provide no evidence for extrapulmonary activity of inhaled particles within the time of exposure and at the concentration evaluated in the present study. PM2.