: Endothelial dysfunction is one of the earliest pathological effects of cigarette smoking. It has recently been suggested that endothelial progenitor cells (EPCs) could contribute to ongoing ...endothelial maintenance and repair. Accordingly, we tested the hypothesis that cigarette smoking is associated with EPC dysfunction.
: EPCs were isolated from the peripheral venous blood of 15 healthy smokers and 11 age-matched nonsmokers. The number of EPCs was significantly reduced in smokers versus control subjects (51.6
±
1.9 versus 120.3
±
10.0 per power field,
p
<
0.001). Moreover, the functional activities of EPCs isolated from smokers were severely compromised. First, the proliferative and migratory response of EPCs isolated from smokers were reduced by 75% and 19%, respectively (
p
<
0.05). Second, EPCs from smokers showed an important decreased adherence to HUVECs that had been previously activated with tumor necrosis factor-α (TNF-α) (
p
<
0.01). Finally, the participation of EPCs to tube formation in a matrigel assay was reduced by 38% in smokers versus control subjects (
p
<
0.001). We found that EPCs from smokers had a significant reduction in the expression of the endothelial cell-specific markers (VE-cadherin, KDR, and vWF). Moreover, ROS formation was significantly increased in EPCs from smokers, whereas the serum antioxidant and nitrite levels of smokers were reduced and correlated with impaired EPC number and functional activity.
: Cigarette smoking is associated with a reduced number of EPCs together with an important impairment of EPC differentiation and functional activities. Our results suggest that EPC dysfunction could contribute to impair blood vessel healing and growth in smokers.
Campylobacter infection is a leading cause of bacterial gastroenteritis worldwide, and most clinical cases appear as isolated, sporadic infections for which the source is rarely apparent. From July ...2005 to December 2007 we conducted a prospective case-case study of sporadic, domestically-acquired Campylobacter enteritis in rural versus urban areas and a prevalence study of Campylobacter in animal and environmental sources in the Eastern Townships, Quebec. Isolates were typed using Multilocus Sequence Typing (MLST) to reinforce the case-case findings and to assign a source probability estimate for each human isolate. The risk of human campylobacteriosis was 1.89-fold higher in rural than urban areas. Unconditional multivariate logistic regression analysis identified two independent risk factors associated with human Campylobacter infections acquired in rural area: occupational exposure to animals (OR = 10.6, 95% CI: 1.2-91, p = 0.032), and household water coming from a private well (OR = 8.3, 95% CI: 3.4-20.4, p<0.0001). A total of 851 C. jejuni isolates (178 human, 257 chicken, 87 bovine, 266 water, 63 wild bird) were typed using MLST. Among human isolates, the incidence rates of clonal complexes (CC) CC-21, CC-45, and CC-61 were higher in rural than urban areas. MLST-based source attribution analysis indicated that 64.5% of human C. jejuni isolates were attributable to chicken, followed by cattle (25.8%), water (7.4%), and wild birds (2.3%). Chicken was the attributable source for the majority of cases, independent of residential area, sex and age. The increased incidence in rural compared to urban areas was associated with occupational exposure to animals, particularly cattle among those aged 15-34 years, and with consumption of private well water. Both bovine and water exposure appeared to contribute to the seasonal variation in campylobacteriosis. These results provide a basis for developing public education and preventive programs targeting the risk factors identified.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In the case of patients with Chronic Low Back Pain (cLBP), Functional Restoration Programs (FRP) can improve their condition. Chronicity may reoccur and lead to difficulties in the ability to work ...related to Fear-Avoidance Beliefs, which may depend on lower motor control. Rationale of the study: Whereas a limited clinical scale evaluates these beliefs, our study is justified by the search to define motor control parameters that can be used as quantified indicators of fear-avoidance beliefs associated with work activity.
The aim of this study is to explore whether difficulty in working one year after participating in the FRP was related to low motor control in patients with cLBP.
Two groups were defined as: “the patients who could work one year after FRP” (called W-Group) and “the patients who could not work one year after FRP because of cLBP” (called NW-Group). The clinical analysis is based on the assessment of pain intensity and the Fear-Avoidance Belief Questionnaire (or FABQ). Gait stability and coefficients of attenuation on four back levels were considered.
The NW-Group had a significantly higher FABQ score than the W-Group one year after FRP (p = 0.02) without any difference regarding pain intensity (p = 0.31). The NW-Group (0.11 ± 0.02) presented significantly higher RMS values for the low back in the anteroposterior axis than the W-group (0.09 ± 0.01), showing lower gait stability in the NW-group.
Motor control parameters reveal significant differences between these groups.
Motor control and fear-avoidance beliefs are associated with work.
Hypercholesterolemia is associated with impaired neovascularization in response to ischemia. Potential mechanisms include defective NO bioactivity and a reduction in the number/function of ...endothelial progenitor cells (EPCs). Here we tested the hypothesis that sildenafil, a phosphodiesterase 5 inhibitor that increases NO-driven cGMP levels, could stimulate EPC function and improve ischemia-induced neovascularization in hypercholesterolemic conditions. Apolipoprotein E–deficient (ApoE) mice were treated (or not treated) with sildenafil (40 mg/kg per day in water), and hindlimb ischemia was surgically induced by femoral artery removal. Sildenafil treatment led to an improved blood flow recovery, an increased capillary density, and a reduction of oxidative stress levels in ischemic muscles at day 7 after surgery. Sildenafil therapy is associated with an increased activation of angiogenic transduction pathways, including Akt, p44/42 mitogen-activated protein kinase, and p38. In vitro, sildenafil increases cellular migration and tubule formation of mature endothelial cells (human umbilical vascular endothelial cells) in a cGMP-dependent manner. In vivo, ApoE mice treated with sildenafil exhibit a significant increase in the number of bone marrow–derived EPCs. Moreover, the angiogenic activities of EPCs (migration and adhesion) are significantly improved in ApoE mice treated with sildenafil. In summary, this study demonstrates that sildenafil treatment is associated with improved ischemia-induced neovascularization in hypercholesterolemic ApoE mice. The mechanisms involve beneficial effects on angiogenic transduction pathways together with an increase in the number and the functional activity of EPCs. Sildenafil could constitute a novel therapeutic strategy to reduce tissue ischemia in atherosclerotic diseases.
Using whole genome sequencing of isolates from a cohort of patients with Clostridium difficile infection (CDI) and colonization, we found that incident CDI cases were more likely to be linked to an ...infected than colonized donor.
Abstract
Background
Whole genome sequencing (WGS) studies can enhance our understanding of the role of patients with asymptomatic Clostridium difficile colonization in transmission.
Methods
Isolates obtained from patients with Clostridium difficile infection (CDI) and colonization identified in a study conducted during 2006-2007 at 6 Canadian hospitals underwent typing by pulsed-field gel electrophoresis, multilocus sequence typing, and WGS. Isolates from incident CDI cases not in the initial study were also sequenced where possible. Ward movement and typing data were combined to identify plausible donors for each CDI case, as defined by shared time and space within predefined limits. Proportions of plausible donors for CDI cases that were colonized, infected, or both were examined.
Results
Five hundred fifty-four isolates were sequenced successfully, 353 from colonized patients and 201 from CDI cases. The NAP1/027/ST1 strain was the most common strain, found in 124 (62%) of infected and 92 (26%) of colonized patients. A donor with a plausible ward link was found for 81 CDI cases (40%) using WGS with a threshold of ≤2 single nucleotide polymorphisms to determine relatedness. Sixty-five (32%) CDI cases could be linked to both infected and colonized donors. Exclusive linkages to infected and colonized donors were found for 28 (14%) and 12 (6%) CDI cases, respectively.
Conclusions
Colonized patients contribute to transmission, but CDI cases are more likely linked to other infected patients than colonized patients in this cohort with high rates of the NAP1/027/ST1 strain, highlighting the importance of local prevalence of virulent strains in determining transmission dynamics.
Moderate consumption of red wine is associated with a decreased incidence of cardiovascular diseases in populations with relatively high amount of fat in the diet. However, the mechanisms involved in ...this protective effect are not completely understood. Here we show that moderate consumption of red wine (equivalent to 2 glasses/day in humans) but not ethanol only, improves blood flow recovery by 32% after hind‐limb ischemia in hypercholesterolemic ApoE‐deficient mice. In ischemic tissues, red wine consumption reduces oxidative stress and increases capillary density by 46%. Endothelial progenitor cells (EPCs) have been shown to have an important role in postnatal neovascu‐larization. We found that the number of EPCs is increased by 60% in ApoE mice exposed to red wine. Moreover, the migratory capacity of EPCs is significantly improved in red wine‐drinking mice. The wine used in our study is a cabernet sauvignon from Langue‐doc‐Roussillon, France, which contains a relatively high concentration (4–6 mg/L) of the polyphenolic antiox‐idant resveratrol. We demonstrate that resveratrol can rescue oxidized low‐density lipoprotein (oxLDL)‐in‐duced impairment of in vitro angiogenic activities in human umbilical vein endothelial cells (HUVECs). Res‐veratrol exposure is also associated with increased activation of Akt/eNOS together with a restoration of nitric oxide production in HUVECs exposed to oxLDL. Our study suggests that moderate consumption of red wine improves ischemia‐induced neovascularization in high‐cholesterol conditions by increasing the number and the functional activities of EPCs and by restoring the Akt‐eNOS‐NO pathway.— Lefevre J., Michaud, S.‐E., Haddad, P., Dussault, S., Ménard C., Groleau, J., Turgeon, J., Rivard A. Moderate consumption of red wine (cabernet sauvignon) improves ischemia‐induced neovascularization in ApoE‐deficient mice: effect on endothelial progenitor cells and nitric oxide. FASEB J. 21, 3845–3852 (2007)
Molecular strain typing is essential for deciphering the epidemiology of Campylobacter jejuni infections. We applied two different methods, multilocus sequence typing (MLST) and analysis of the flaA ...short variable repeat (SVR), to 289 isolates (163 human, 56 chicken, 34 raw milk, and 36 environmental water isolates) collected in the province of Québec, Canada, over 3 years; in addition, the analysis included the pulsed-field gel electrophoresis (PFGE) typing results for a subset of 131 isolates studied previously. MLST defined 96 sequence types (STs) and 20 clonal complexes (CCs), including 49 STs (73 isolates, 25%) and 39 alleles not previously documented in an international database. The frequency of new STs was significantly higher among water isolates than among isolates from other sources (18/36 50% and 55/253 22%, respectively; P < 0.001). Nine of the 10 most prevalent CCs included isolates from humans and at least one other source; five CCs comprised exclusively or mostly human and chicken isolates. However, water and milk were the predominant nonhuman sources among the remaining CCs, suggesting that sporadic C. jejuni infections in humans may frequently arise from sources other than chickens. All three typing systems were discriminatory (discriminatory index > 0.9). Among 131 isolates analyzed by PFGE, each of the 20 types represented by two or more isolates corresponded to a single CC. In contrast, among the 14 most prevalent types detected by analysis of the flaA SVR (5 to 27 isolates each), 8 (57%) included isolates that represented multiple different CCs. The basis for these discordant results was uncertain. Antimicrobial resistance was randomly distributed among the CCs and appeared to be more closely related to the source of an isolate than its genotype. Although MLST is labor-intensive and expensive, it remains the single best method for the genotyping of C. jejuni isolates and deciphering the epidemiologic relationships among isolates.
Staphylococcus aureus and Pseudomonas aeruginosa are often found together in the airways of cystic fibrosis (CF) patients. It was previously shown that the P. aeruginosa exoproduct ...4-hydroxy-2-heptylquinoline-N-oxide (HQNO) suppresses the growth of S. aureus and provokes the emergence of small-colony variants (SCVs). The presence of S. aureus SCVs as well as biofilms have both been associated with chronic infections in CF.
We demonstrated that HQNO stimulates S. aureus to form a biofilm in association with the formation of SCVs. The emergence of SCVs and biofilm production under HQNO exposure was shown to be dependent on the activity of the stress- and colonization-related alternative sigma factor B (SigB). Analysis of gene expression revealed that exposure of a prototypical S. aureus strain to HQNO activates SigB, which was leading to an increase in the expression of the fibronectin-binding protein A and the biofilm-associated sarA genes. Conversely, the quorum sensing accessory gene regulator (agr) system and the alpha-hemolysin gene were repressed by HQNO. Experiments using culture supernatants from P. aeruginosa PAO1 and a double chamber co-culture model confirmed that P. aeruginosa stimulates biofilm formation and activates SigB in a S. aureus strain isolated from a CF patient. Furthermore, the supernatant from P. aeruginosa mutants unable to produce HQNO induced the production of biofilms by S. aureus to a lesser extent than the wild-type strain only in a S. aureus SigB-functional background.
These results suggest that S. aureus responds to HQNO from P. aeruginosa by forming SCVs and biofilms through SigB activation, a phenomenon that may contribute to the establishment of chronic infections in CF patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Endothelial dysfunction is one of the earliest pathological effects of cigarette smoking. Vascular endothelial growth factor (VEGF) has been shown to be an important regulator of endothelial healing ...and growth. Accordingly, we tested the hypothesis that cigarette smoke exposure impairs VEGF actions in endothelial cells. In human umbilical vein endothelial cells (HUVECs), cigarette smoke extracts (CSE) inhibited VEGF-induced tube formation in the matrigel assay. CSE did not affect HUVECs proliferation, but significantly reduced cellular migration in response to VEGF. This impaired migratory activity was associated with a reduced expression of αvβ3, αvβ5, α5β1 and α2β1 integrins. The Akt/eNOS/NO pathway has been shown to be important for VEGF-induced endothelial cell migration. We found that CSE inhibited Akt/eNOS phosphorylation and NO release in VEGF-stimulated HUVECs. This was associated with an increased generation of reactive oxygen species (ROS). Importantly, in HUVECs exposed to CSE, treatment with antioxidants (NAC, vitamin C) reduced ROS formation and rescued VEGF-induced NO release, cellular migration and tube formation. Moreover, treatment with NO donors (SNAP, SNP) or a cGMP analog (8-Br-cGMP) rescued integrin expression, cellular migration and tube formation in endothelial cells exposed to CSE. (1) Cigarette smoke exposure impairs VEGF-induced endothelial cell migration and tube formation. (2) The mechanism involves increased generation of ROS, decreased expression of surface integrins together with a blockade of the Akt/eNOS/NO pathway. (3) These findings could contribute to explain the negative effect of cigarette smoking on endothelial function and vessel growth.
Mica is the most important carrier of rare alkalis (Li, Rb and Cs) and volatiles, and also a major host of rare metals such as Sn, W, Nb and Ta. Thus, the knowledge of trace element partitioning ...between mica and silicate melt is crucial to understand enrichment mechanisms of ore metals in evolved silicic systems. However, experimental data are scarce, mainly because the synthesis of large mica grains which can be analyzed with laser ablation techniques is challenging. To address this issue, we conducted two-step experiments, using a high-temperature step at 800 °C, and a low-temperature step at 600 °C with a temperature cycling interval of 30 °C, and variable run durations from 21 to 60 days. The experimental products, at 600 °C, 200 MPa, are mainly composed of mica and alkali feldspars. Ferroholmquistite (Fhlm; a Li-bearing amphibole) was also observed in the Li-bearing systems.
Beryllium, Zn and Cs are highly incompatible in all run products with mineral/melt partitioning of mineral/meltDBe between 0.01 and 0.08, mineral/meltDZn between < 0.01 and 0.24 and mineral/meltDCs between <0.01 and 0.19. Gallium is mildly incompatible in mica and feldspars with mica/meltDGa, K-feld/meltDGa and Na-feld/meltDGa of 0.24–0.35, 0.60–0.67 and 0.69–0.72, respectively, whereas Fhlm/meltDGa is nearly 1. Rubidium is characterized by a slight enrichment in mica and K-rich feldspar with respect to melt. Niobium and Ta are highly incompatible in feldspars, while they are compatible in ferroholmquistite. Li-mica crystallization would cause Nb/Ta fractionation with mica/meltDNb and mica/meltDTa of 4.46 and 0.88, respectively. Tungsten is preferentially incorporated in Li-rich mica with mica/meltDW > 22. The strong partitioning of W into Li-rich mica implies that minor Li-rich mica fractionation (>5 %) will strongly deplete W in the residual melt, thus inhibiting transfer to the magmatic fluid at the magmatic-hydrothermal transition. Based on the observed mineral/meltD value, a multi-stage quantitative fractionation model for the behavior of metals during the crystallization of Li-bearing granitic magmas was developed. The results suggest that crystal fractionation is an effective mechanism that could further enrich Be, Ga, Rb, Cs, Nb and Ta in residual melts. Li-rich mica and muscovite are more effective in causing Nb/Ta fractionation as compared with biotite. The very low Nb/Ta ratios found in natural granite may have resulted via extreme, i.e., >99 wt% of fractional crystallization, even if without the precipitation of columbite-group minerals or increasing hydrothermal activity. Due to the very high Li-mica/meltDW value, water saturation in the melt and subsequent magmatic fluid exsolution should occur before Li-mica starts to crystallize to avoid W sequestration in the magma. At 175 MPa, the efficiency of extracting W from Li-poor granitic system is at least 15 % higher than that from Li-rich granitic system. Li-poor granitic systems are thus expected to have a greater W-mineralization potential than Li-rich system, which is consistent with the fact that most parental magmas of large/giant W deposits are Li-poor in composition.
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