Higher Levels Of Neutrophils Research Articles

Risk of Thrombus Fragmentation during Endovascular Stroke Treatment

Periprocedural thrombus fragmentation is a relevant risk in endovascular stroke treatment. Because factors influencing its occurrence are largely unknown, this study addresses a potential relationship between thrombus histology and clot stability. Eighty-five patients with anterior circulation stroke treated with thrombectomy were included in this retrospective study. The number and location of emboli after retrieving the primary thrombus, the number of maneuvers, and TICI scores were evaluated. H&E and neutrophil elastase staining of retrieved clots was performed, and semiquantitative measurements of thrombus components were correlated with procedural parameters. An inverse correlation between maneuvers required for thrombus retrieval and the number of distal and intermediate emboli was observed (Spearman r, -0.23; P = .032). Younger patients were at higher risk for periprocedural thrombus fragmentation (Spearman r, -0.23; P = .032). Bridging thrombolysis tended to be associated with fewer maneuvers (2 vs 3, P = .054) but more emboli (1 vs 0, P = .067). While no consistent correlation between procedural parameters and red/white blood cells and fibrin-/platelet fractions could be found, higher amounts of neutrophil elastase-positive cells within the thrombus were independently associated with the occurrence of multiple emboli (adjusted OR, 4.6; 95% CI, 1.1-19.7; P = .041) and lower rates of complete recanalization (adjusted OR, 0.3; 95% CI, 0.1-0.9; P = .050). Younger age, easy-to-retrieve thrombi, and bridging thrombolysis may be risk factors for periprocedural thrombus fragmentation. Findings from standard histologic stains did not provide insight into thrombectomy-relevant thrombus stability. However, higher neutrophil levels in the thrombus tissue were related to an increased risk of periprocedural thrombus fragmentation. This observation aligns with the proposed thrombolytic capacity of neutrophil elastase and points to its potential clinical relevance in the context of stroke thrombectomy.

Sickle cell anemia - Nitric oxide related genetic modifiers of hematological and biochemical parameters.

Sickle cell anemia (SCA) is an inherited blood disorder. SCA patients present clinical and hematologic variability that cannot be only explained by the single mutation in the beta-globin gene. Others genetic modifiers and environmental effects are important for the clinical phenotype. SCA patients present arginine deficiency that contributes to a lower nitric oxide (NO) bioactivity. The aim of this work is to determine the association between hematological and biochemical parameters and genetic variants from eNOS gene, in pediatric SCA patients. 26 pediatric SCA patients were genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques in three important eNOS gene polymorphisms - rs2070744, rs1799983 and intron 4 VNTR. Results from this study show a significant statistical association between some parameters and genetic variants: an increased reticulocyte count and high serum lactate dehydrogenase levels were associated with both the rs2070744_TT and the rs1799983_GG genotypes at eNOS gene and high levels of neutrophils were associated with the eNOS4a allele at intron 4 VNTR. Our results reinforce the importance of NO bioactivity in SCA. We presume that NO, and its precursors might be used as therapy to improve the quality of life of SCA patients.

The Differential Contribution of the Innate Immune System to a Good Pathological Response in the Breast and Axillary Lymph Nodes Induced by Neoadjuvant Chemotherapy in Women with Large and Locally Advanced Breast Cancers.

The tumour microenvironment consists of malignant cells, stroma, and immune cells. The role of adaptive immunity in inducing a pathological complete response (pCR) in breast cancer with neoadjuvant chemotherapy (NAC) is well studied. The contribution of innate immunity, however, is poorly documented. Breast tumours and axillary lymph nodes (ALNs) from 33 women with large and locally advanced breast cancers (LLABCs) undergoing NAC were immunohistochemically assessed for tumour-infiltrating macrophages (TIMs: M1 and M2), neutrophils (TINs), and dendritic cells (TIDCs) using labelled antibodies and semiquantitative methods. Patients' blood neutrophils (n = 108), DCs (mDC1 and pDC), and their costimulatory molecules (n = 30) were also studied. Pathological results were classified as pCR, good (GPR) or poor (PRR). In breast and metastatic ALNs, high levels of CD163+ TIMs were significantly associated with a pCR. In blood, high levels of neutrophils were significantly associated with pCR in metastatic ALNs, whilst the % of mDC1 and pDC and expression of HLA-DR, mDC1 CD40, and CD83 were significantly reduced. NAC significantly reduced tumour DCs but increased blood DCs. PPRs to NAC had significantly reduced HLA-DR, CD40, and CD86 expression. Our study demonstrated novel findings documenting the differential but important contributions of innate immunity to pCRs in patients with LLABCs undergoing NAC.

Relationship between Neutrophil-to-Lymphocyte Ratio and Stress in Multiple Sclerosis Patients.

Multiple Sclerosis (MS), a disease of autoimmunity and inflammation, is characterized by deterioration of the myelin sheath that protects the nerve fibers. The high levels of neutrophils in serum may be related to the chronic inflammation and caused by other triggers such as infections that have been associated with relapses in MS. To investigate the value of Neutrophil/Lymphocyte Ratio (NLR) as a possible marker and relationship with Depression, Anxiety and Stress (DAS) score in MS patients. A total of 60 MS patients and 60 age and sex matched healthy controls were recruited for the present study. We measured DAS score, NLR, calcium, phosphate, magnesium, chloride, alkaline phosphatase, albumin in serum levels in MS patients and in healthy controls. The mean age was not significantly different in both case and control groups. The case and control groups were similar in terms of sex; however, the majority of the MS group was female. The NLR values of MS patients were significantly higher than those of the healthy controls (p=<0.001). The NLR values were also significantly (p<0.001) correlated with stress score. NLR could be considered as a quick, cheap, easily measurable and inflammatory marker for assessment of inflammation in MS patients. The role of NLR in MS must be explored further.

Relationship between oxidative stress and haematological indices in patients with diabetes in the Ghanaian population.

BackgroundPersistent hyperglycaemia is a hallmark of Diabetes Mellitus (DM). It causes increased production of free radicals, especially reactive oxygen species (ROS), — resulting in oxidative stress. Reactive Oxygen Species have been implicated in the development of haematological complications in patients with diabetes. Superoxide Dismutase (SOD) is one of the most effective antioxidant enzyme defense systems against free radicals.MethodsFrom February through May 2014, we assessed the relationship between oxidative stress and haematological profiles among individuals with and without diabetes. A cross sectional study of 66 case patients and 44 age-matched controls were recruited from the National Diabetes Management and Research Centre (NDMRC), Korle-Bu Teaching Hospital, Accra, Ghana. Blood samples were obtained from study participants with consent. We determined the haematological profiles of study participants and measured their oxidative stress levels using a standardized kit for SOD activity.ResultsHigher white blood cell (WBC) counts were seen in the diabetes cohort (p-value = 0.023). The SOD activity tended to be lower in diabetes patients (p–value = 0.144 however) while higher neutrophil levels seemed to correlate with SOD activity (R = 0.249; R2 = 6.2 %; p-value = 0.049). There did not appear to be a correlation between fasting blood glucose (FBG) and SOD activity (R = −0.044; p-value = 0.727).ConclusionThe study reports similar oxidative stress levels, as measured by SOD activity, in diabetic and non-diabetic adults. The SOD activity did not appear to correlate with FBG and several other haematological parameters. Further study would be required to investigate the relationship between these haematological indices and diabetic micro- and macro-vascular complications in our population.

Innate and adaptive cellular phenotypes contributing to pulmonary disease in mice after respiratory syncytial virus immunization and infection

Respiratory syncytial virus (RSV) is the major leading cause of infantile viral bronchiolitis. However, cellular phenotypes contributing to the RSV protection and vaccine-enhanced disease remain largely unknown. Upon RSV challenge, we analyzed phenotypes and cellularity in the lung of mice that were naïve, immunized with formalin inactivated RSV (FI-RSV), or re-infected with RSV. In comparison with naïve and live RSV re-infected mice, the high levels of eosinophils, neutrophils, plasmacytoid and CD11b+ dendritic cells, and IL-4+ CD4+ T cells were found to be contributing to pulmonary inflammation in FI-RSV immune mice despite lung viral clearance. Alveolar macrophages appeared to play differential roles in protection and inflammation upon RSV infection of different RSV immune mice. These results suggest that multiple innate and adaptive immune components differentially contribute to RSV disease and inflammation.

Metastasis in the Light

Cancer![Figure][1] CREDIT: © RISAMAY/ISTOCKPHOTO Cutaneous melanoma is less common than other forms of skin cancer but is far more deadly, especially if not detected at an early stage. Ultraviolet (UV) light from the Sun plays a key role in the initiation of melanoma by inducing mutations in the DNA of melanocytes, the pigment-producing cells in skin. A new study suggests that UV light does damage well beyond this early role: It appears to trigger a chain of pathologic events that facilitate metastasis. Studying a mouse model, Bald et al. found that repetitive exposure of primary melanomas to UV light did not increase tumor incidence or growth but rather increased the number of lung metastases. Closer examination revealed that UV light induced the recruitment of certain immune cells (neutrophils) to the primary tumor. This inflammatory response in turn activated endothelial cells (cells that line blood vessels) and triggered migration of the melanoma cells toward them, resulting in the expansion of tumor cells along blood vessels. This “angiotrophic” growth pattern is thought to increase the likelihood that tumor cells enter the bloodstream and metastasize. Consistent with this, human melanoma samples with high levels of neutrophils were more metastatic. Nature 10.1038/nature13111 (2014). [1]: pending:yes

Insulin Treatment Modulates the Host Immune System To Enhance Pseudomonas aeruginosa Wound Biofilms

Diabetes affects 25.8 million people in the United States, or 8.3% of the population, and these numbers are even higher in developing countries. Diabetic patients are more susceptible to the development of chronic wounds with debilitating bacterial infections than nondiabetics. Previously, we compared the ability of the opportunistic pathogen Pseudomonas aeruginosa to cause biofilm-associated infections in chronic wounds of diabetic and nondiabetic mice (C. Watters, K. DeLeon, U. Trivedi, J. A. Griswold, M. Lyte, K. J. Hampel, M. J. Wargo, and K. P. Rumbaugh, Med. Microbiol. Immunol. 202:131-141, 2013). Unexpectedly, we observed that insulin-treated diabetic mice had significantly more biofilm in their wounds, which correlated with higher antibiotic tolerance. Here, we investigated whether insulin treatment modulates the diabetic immune system to favor P. aeruginosa biofilm formation. Utilizing a murine chronic wound model, we found that DNA protected P. aeruginosa in the wounds of insulin-treated diabetic mice from antibiotic treatment. We also observed increased numbers of neutrophils, reduced numbers of macrophages, and increased cell death in the wounds of diabetic mice on insulin therapy. Taken together, these data suggest that high levels of lysed neutrophils in the wounds of diabetic mice on insulin, combined with fewer macrophages to remove the cellular debris, contribute to increased DNA levels, which enhance P. aeruginosa biofilms.

Propofol sedation in total knee replacement

This study aimed to show the effect of propofol sedation on oxidative stress and inflammation resulting from ischemia-reperfusion. After having obtained written informed consent from the patients and ethics committee approval, 36 patients were randomly allocated to 2 groups: group C, control and group P, propofol. Spinal anesthesia was administered to both groups with 15 mg bupivacaine. Patients in group P received a propofol infusion of 2 mg/kgBW/h and the patients in group C received a placebo infusion in an equal dose. Malondialdehyde (MDA), superoxide dismutase (SOD) and the total antioxidative capacity (TAC) levels were measured in venous blood samples prior to propofol or placebo administration (preischemia T0), 30 min after placing the tourniquet (ischemia T1) and 2 h after deflation of the tourniquet (reperfusion T2). High sensitivity C-reactive protein (hsCRP) and neutrophil levels were measured before propofol was administered (T0) and 12 h after reperfusion (T3). While serum MDA and SOD levels were significantly higher during the reperfusion period than the preischemic period, TAC levels were found to be low in the control group (p < 0.05). In the propofol group there were no differences between the preischemia-reperfusion periods with respect to MDA, SOD and TAC levels (p > 0.05). The neutrophil and hsCRP levels were observed to be increased to a lesser extent in the propofol group compared to the control group (p < 0.05). Propofol infusion in addition to spinal anesthesia may reduce oxidative damage and the inflammatory response developing due to the tourniquet in total knee replacement surgery.

Monitoring Therapeutic Treatments against Burkholderia Infections Using Imaging Techniques

Burkholderia mallei, the etiologic agent of glanders, are Category B select agents with biothreat potential, and yet effective therapeutic treatments are lacking. In this study, we showed that CpG administration increased survival, demonstrating protection in the murine glanders model. Bacterial recovery from infected lungs, liver and spleen was significantly reduced in CpG-treated animals as compared with non-treated mice. Reciprocally, lungs of CpG-treated infected animals were infiltrated with higher levels of neutrophils and inflammatory monocytes, as compared to control animals. Employing the B. mallei bioluminescent strain CSM001 and the Neutrophil-Specific Fluorescent Imaging Agent, bacterial dissemination and neutrophil trafficking were monitored in real-time using multimodal in vivo whole body imaging techniques. CpG-treatment increased recruitment of neutrophils to the lungs and reduced bioluminescent bacteria, correlating with decreased bacterial burden and increased protection against acute murine glanders. Our results indicate that protection of CpG-treated animals was associated with recruitment of neutrophils prior to infection and demonstrated, for the first time, simultaneous real time in vivo imaging of neutrophils and bacteria. This study provides experimental evidence supporting the importance of incorporating optimized in vivo imaging methods to monitor disease progression and to evaluate the efficacy of therapeutic treatment during bacterial infections.

The Emerging Role of Tiotropium for Patients with Asthma

To review clinical data on the use of the long-acting anticholinergic agent tiotropium in patients with asthma. A literature search was performed via EMBASE and MEDLINE (1966-November 2012). The search was limited to human data published in the English language. Search terms included asthma, tiotropium, and long-acting anticholinergics. Relevant information related to the use of tiotropium in patients with asthma was reviewed. Randomized controlled trials and open-label trials were included. The references of published articles identified in the search were also examined for additional studies appropriate to include in the review. Data were prioritized if they originated from human studies, especially if derived from randomized, placebo-controlled trials. Trials and case reports involving the use of long-acting anticholinergic tiotropium in asthma patients were included; conversely, trials involving ipratropium were not. Two large randomized controlled trials support the safety and efficacy of adding tiotropium to the treatment regimen of select patients with poorly controlled asthma already receiving combination high-dose glucocorticosteroid/long-acting β-agonist (LABA) therapy. Pharmacogenomic studies have shown that patients with polymorphisms of the β2-adrenoreceptor (ADRB2; 16 Arg/Arg and 16 Arg/Gly) are particularly responsive to treatment with tiotropium. Smaller studies indicate that the advantages may be most pronounced in patients with a predominance of sputum neutrophils and that tiotropium can assist with decreasing the inhaled corticosteroid (ICS) dose. An increased risk of cardiovascular events was not identified. Tiotropium should be considered in patients with asthma who remain symptomatic while receiving high-dose ICS and LABA therapy. Specifically, patients with high sputum neutrophil levels or with 16 Arg/Arg or 16 Arg/Gly polymorphism of the ADRB2 gene appear to respond best.

Cross-sectional changes in patterns of allostatic load among persons with varying disabilities, NHANES: 2001–2010

BackgroundAllostatic Load (AL) is a measure of physiological stress that correlates with morbidity and mortality. ObjectiveThe purpose of this study was to evaluate patterns of AL among persons with each of eight categories of disability versus persons with no disabilities over the 10-year Healthy People 2010 examination period. MethodsThe study examined measures of AL from the 2001–2010 National Health and Nutrition Examination Survey (NHANES). The independent variable was Disability Status (hearing, vision, memory, physical–mental–emotional, walking up 10 steps, bending or kneeling, lifting or carrying, assistive devices, no disability). Eight laboratory and one social AL dependent variables included blood pressure, body mass index (BMI), HDL cholesterol, number of friends, and neutrophil percentages. Weighted statistical analyses included one-way ANCOVA with age as the covariate and chi-square tests. ResultsAmong respondents, 2.3% had hearing disabilities; 14.0% vision disabilities, 4.6% memory disabilities; 1.5% physical, mental, emotional disabilities; 1.3%, 5.9%, and 3.5% various mobility disabilities; and 5.3% used assistive devices. Persons with disabilities had significantly higher BMI, lower HDL cholesterol, higher C-reactive protein, and higher neutrophil levels than persons without disabilities. Systolic and diastolic blood pressures decreased during the decade, but BMI increased. A range of 36.2–61.0% of persons with non-hearing disabilities exceeded BMI obesity thresholds during 2009, and 13.8–29.9% had fewer than three friends during 2009. ConclusionsThese findings support previous research linking risks for secondary conditions/morbidity and allostatic load while demonstrating associations between disabilities and AL, especially for persons with mobility disabilities.

MMP-8 overexpression and persistence of neutrophils relate to stress-impaired healing and poor collagen architecture in mice

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) are critical for tissue remodeling during wound repair. Psychological stress has been found to impair wound healing in humans and animals. The objective of this study was to assess MMP and TIMP gene expression during stress-impaired healing. Female SKH-1 mice (n=299) were divided into control and stress groups (13h restraint/day for 3days prior to and 5days post-wounding). Two 3.5mm cutaneous full-thickness wounds were placed on the dorsum of each mouse and wound measurements were performed daily. RT-PCR for gene expression of MMP-2, MMP-8, MMP-9, TIMP-1 and TIMP-2 was performed at days 1, 3 and 5. Immunohistochemical analyses of the healed wounds were performed at days 15 and 28. As expected, wounds healed more slowly in restraint-stressed mice compared to controls. Stressed mice exhibited MMP-8 overexpression and lower TIMP-1 levels during healing, and poorer collagen organization once healed. MMP-8 overexpression may have stemmed from a higher level of neutrophils, observed in wound tissue on days 3 and 5. These findings implicate higher neutrophil numbers, MMP-8 overexpression, and TIMP-1 under-expression, as mechanisms that may compromise wound outcomes such as scarring under conditions of stress.

Erythropoiesis versus inflammation in Hereditary Spherocytosis clinical outcome

ObjectivesThis study aimed to evaluate the relationship between erythropoiesis and inflammation, in Hereditary Spherocytosis (HS) clinical outcome. Design and methodsWe studied 26 controls and 82 HS patients presenting mild (n=49) and severer (n=33) HS forms. We evaluated plasma levels of EPO, sTfR, ferritin, iron, folic acid, vitamin B12, TNF-α, IFN-γ, elastase and lactoferrin; leukocyte and reticulocyte counts and RPI were determined. ResultsAll HS patients showed significantly higher EPO, sTfR, reticulocytes and RPI but only mild HS presented normal hemoglobin levels; the positive significant correlations between EPO and sTfR, reticulocytes and RPI observed in mild HS were not observed in severer HS patients. HS patients presented with higher levels of neutrophils, TNF-α, IFN-γ, elastase, lactoferrin and ferritin. ConclusionsOur data show HS as a disease linked to enhanced erythropoiesis that is disturbed in the more severe forms, to which inflammation may contribute, at least in part.

Expiratory flows and airway inflammation in elderly asthmatic patients

Asthma in the elderly is often underrecognized and suboptimally treated, resulting in an increased morbidity and mortality. The characteristics of asthma-related bronchitis and its optimal treatment remain to be determined in this population. We aimed to compare lung function and airway inflammation in elderly and younger asthmatic subjects. Data from two induced sputum databases were analyzed in three groups of asthmatic subjects (18-30 y, n = 136; 31-59 y, n = 385; 60-72 y, n = 172) and one group of healthy elderly subjects (60-89 y, n = 16). Expiratory flows and induced sputum cell counts were analyzed. Airway obstruction was more marked in elderly asthmatics compared with healthy elderly or younger asthmatic subjects (p < 0.01). An increase in sputum neutrophils and a decrease in macrophages and lymphocytes were observed in elderly asthmatics (p < 0.0001). Neutrophil percentages significantly increased with asthma severity in the young and the middle-aged groups, while they remained similar in elderly asthmatics regardless of asthma severity (p < 0.05). Neutrophil percentages weakly correlated with the dose of ICS in all asthmatics (r = 0.17, p < 0.0001). Age and dose of ICS were independent predictors of neutrophil percentage in asthmatic subjects in a regression model (R(2) = 0.12). Asthma in the elderly is associated with a more marked airway obstruction and sputum neutrophilia. Both age and the dose of corticosteroids need to be considered in the interpretation of the clinical relevance of sputum neutrophil count.

YopJ-Promoted Cytotoxicity and Systemic Colonization Are Associated with High Levels of Murine Interleukin-18, Gamma Interferon, and Neutrophils in a Live Vaccine Model ofYersinia pseudotuberculosisInfection

Several Yersinia species have been utilized as live attenuated vaccines to prime protective immunity against yersiniae and other pathogens. A type III secretion system effector known as YopJ in Y. pseudotuberculosis and Y. pestis and YopP in Y. enterocolitica has been shown to regulate host immune responses to live Yersinia vaccines. YopJ/P kills macrophages and dendritic cells, reduces their production of tumor necrosis factor alpha (TNF-alpha) and interleukin-12 (IL-12), and promotes systemic colonization in mouse models of intestinal Yersinia infection. Furthermore, YopP activity decreases antigen presentation by dendritic cells, and a yopP mutant of a live Y. enterocolitica carrier vaccine elicited effective priming of CD8 T cells to a heterologous antigen in mice. These results suggest that YopJ/P activity suppresses both innate and adaptive immune responses to live Yersinia vaccines. Here, a sublethal intragastric mouse infection model using wild-type and catalytically inactive yopJ mutant strains of Y. pseudotuberculosis was developed to further investigate how YopJ action impacts innate and adaptive immune responses to a live vaccine. Surprisingly, YopJ-promoted cytotoxicity and systemic colonization were associated with significant increases in neutrophils in spleens and the proinflammatory cytokines IL-18 and gamma interferon (IFN-gamma) in serum samples of mice vaccinated with Y. pseudotuberculosis. Secretion of IL-18 accompanied YopJ-mediated killing of macrophages infected ex vivo with Y. pseudotuberculosis, suggesting a mechanism by which this effector directly increases proinflammatory cytokine levels in vivo. Mice vaccinated with the wild-type strain or the yopJ mutant produced similar levels of antibodies to Y. pseudotuberculosis antigens and were equally resistant to lethal intravenous challenge with Y. pestis. The findings indicate that a proinflammatory, rather than anti-inflammatory, process accompanies YopJ-promoted cytotoxicity, leading to increased systemic colonization by Y. pseudotuberculosis and potentially enhancing adaptive immunity to a live vaccine.

Carcinoembryonic antigen and neutrophils in healthy smokers

We measured the levels of carcinoembryonic antigen (CEA) and the concentrations of neutrophils in serum from healthy smokers. The smokers (n = 1396) had more leukocytes, neutrophils, and lymphocytes than did non-smokers (n = 1123) (leukocytes: 5853 +/- 1627/mm3 vs 4564 +/- 1118/mm3, p < 0.0001; neutrophils: 3533 +/- 1280/mm3 vs 2718 +/- 883/mm3, p < 0.0001; lymphocytes; 1843 +/- 502/mm3 vs 1513 +/- 406/mm3, p < 0.0001). Subjects in whom the levels of CEA was greater than 5.0 ng/ml had significantly higher concentrations of leukocytes, neutrophils and lymphocytes than did those in whom it was 5.0 ng/ml or less (p < 0.0001). Weak correlations were found between serum CEA levels and both the duration of smoking and the Brinkman index. The CEA levels also correlated with daily cigarette consumption (rho = 0.53, p < 0.0001). The concentration of neutrophils in subjects who smoked no more than 20 cigarettes per day or had a CEA level greater than 5.0 ng/ml, or both, was higher than that in subjects who smoked more than 20 cigarettes per day or had a CEA level less than or equal to 5.0 ng/ml, or both (4097 +/- 1325/mm3 vs 3791 +/- 1278/mm3, p < 0.05). These results suggest that in healthy smokers, high serum CEA levels are related to high neutrophil levels.

Genetic Variation of the Human Urinary Tract Innate Immune Response and Asymptomatic Bacteriuria in Women

BackgroundAlthough several studies suggest that genetic factors are associated with human UTI susceptibility, the role of DNA variation in regulating early in vivo urine inflammatory responses has not been fully examined. We examined whether candidate gene polymorphisms were associated with altered urine inflammatory profiles in asymptomatic women with or without bacteriuria.MethodologyWe conducted a cross-sectional analysis of asymptomatic bacteriuria (ASB) in 1,261 asymptomatic women ages 18-49 years originally enrolled as participants in a population-based case-control study of recurrent UTI and pyelonephritis. We genotyped polymorphisms in CXCR1, CXCR2, TLR1, TLR2, TLR4, TLR5, and TIRAP in women with and without ASB. We collected urine samples and measured levels of uropathogenic bacteria, neutrophils, and chemokines.Principal FindingsPolymorphism TLR2_G2258A, a variant associated with decreased lipopeptide-induced signaling, was associated with increased ASB risk (odds ratio 3.44, 95%CI; 1.65–7.17). Three CXCR1 polymorphisms were associated with ASB caused by gram-positive organisms. ASB was associated with urinary CXCL-8 levels, but not CXCL-5, CXCL-6, or sICAM-1 (P≤0.0001). Urinary levels of CXCL-8 and CXCL-6, but not ICAM-1, were associated with higher neutrophil levels (P≤0.0001). In addition, polymorphism CXCR1_G827C was associated with increased CXCL-8 levels in women with ASB (P = 0.004).ConclusionsTLR2 and CXCR1 polymorphisms were associated with ASB and a CXCR1 variant was associated with urine CXCL-8 levels. These results suggest that genetic factors are associated with early in vivo human bladder immune responses prior to the development of symptomatic UTIs.

Septic Arthritis of the Temporomandibular Joint: A Retrospective Review of 40 Cases

Septic arthritis of the temporomandibular joint is an uncommonly reported entity. The aim of the present study was to review the cases treated at our clinic, analyze the characteristics of this disease and the responses to management, and recommend a protocol for managing suspected cases. A total of 40 consecutive patients were included from 1995 to 2007. Their demographics, predisposing factors, clinical manifestations, radiologic findings, joint fluid analysis results, treatment, and outcomes were reviewed. The 40 patients included 26 men and 14 women, with an average age of 36 years. Original infections were found in 15 patients (local spread in 4 and hematogenous dissemination from a distant site in 11). All patients complained of trismus and tenderness in the temporomandibular joint. Sudden malocclusion was found in 33 patients. Joint space widening and limitation of condyle movement were demonstrated by plain film in 33 patients. Increased joint effusion was confirmed by magnetic resonance imaging in 7 patients. Joint fluid was obtained from 35 patients. A high level of neutrophils and fibrin were found under microscopy with hematoxylin-eosin staining. Staphylococcus saprophyticus and S. aureus were cultured from 5 patients. Arthrocentesis under low pressure was applied to 35 patients, and arthroscopy was used in 9 patients. Major sequelae occurred in 11 patients, including fibrosis in 2 and postinfectious osteoarthritis in 9. Septic arthritis of the temporomandibular joint mainly arises from hematogenous spread, but the original infection is often occult. Antibiotic therapy, arthrocentesis under low pressure, and joint immobilization are recommended for patients in the acute stage. The common sequela is osteoarthritis.

Occupational exposure to bacterial single cell protein induces inflammation in lung and blood

Bacterial single cell protein (BSCP) is used as a protein enrichment in livestock and fish feed, and is extracted from dried bacterial mass. In the production of BSCP, workers are exposed to organic dust containing high levels of endotoxins that may induce acute airway inflammation. However, the long term effect on the airways of such exposure is not known, and we have examined inflammatory markers in induced sputum and blood among BSCP exposed workers. We included 21 non-smoking production workers (age 31–42 (range; mean 35)) without respiratory symptoms and 21 healthy non-exposed references (age 21–52 (range; mean 34)). Airborne endotoxin concentrations were measured, and induced sputum samples and blood samples were collected from the workers and non-exposed references. The airborne endotoxin concentration measured in inhaled air during the work shift was 430 EU/m3 (50–2000) (median (range)). The percentage of neutrophils in induced sputum was 79% (66–93) (median (25th–75th percentiles)) and 31% (25–45) (p < 0.001) for operators and references, respectively. Protein analysis in induced sputum supernatant showed significantly elevated levels of interleukins IL-1β and IL-12 (p < 0.05), while blood analysis showed significantly elevated levels of PDGF-BB (platelet-derived growth factor-BB) and RANTES (regulated upon activation normally T cell expressed and secreted) (p < 0.05). Workers exposed to BSCP had an airway inflammation characterized by a high level of neutrophils. However, only a few cytokines were elevated in lung and blood, which could imply low inflammatory activity suggestive of possible adaptation mechanisms due to daily exposure to BSCP, or that the inflammation reaction was a dose-related response occurring at higher levels.